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Appendix:Recommendations from the Working Group for the International Consensus Guidelines for Chronic Pancreatitis in collaboration with the International Association of Pancreatology, American Pancreatic Association, Japan Pancreas Society and European Pancreatic ClubAsbj?rn M Drewes1, Stefan A W Bouwense2, Claudia M Campbell3, Güralp O Ceyhan4, Myriam Delhaye5, Ihsan Ekin Demir4, Pramod K Garg6, Harry van Goor2, Christopher Halloran7, Shuiji Isaji8, John P Neoptolemos7, S?ren S Olesen1, Tonya Palermo9, Pankaj Jay Pasricha10, Andrea Sheel7, Tooru Shimosegawa11, Eva Szigethy12, David C Whitcomb13 & Dhiraj Yadav13, for the Working group for the International (IAP – APA – JPS – EPC) Consensus Guidelines for Chronic Pancreatitis1. Centre for Pancreatic Diseases, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Denmark2. Department of Surgery, Radboud University Medical Center, Nijmegen, the Netherlands 3. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, USA4. Department of Surgery, Klinikum rechts der Isar, Technische Universit?t München, Munich, Germany 5. Department of Gastroenterology, Erasme University Hospital, Brussels, Belgium 6. Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India7. Institute of Translational Medicine, University of Liverpool, United Kingdom8. Department of Surgery, Mie University Graduate School of Medicine, Japan9. Seattle Children's Hospital Research Institute, Washington School of Medicine, USA10. Center for Neurogastroenterology, Johns Hopkins University School of Medicine, Baltimore, USA11. Department of Gastroenterology. Tohoku University Graduate School of Medicine, Japan12. Visceral Inflammation and Pain Center, Division of Gastroenterology, University of Pittsburgh and UPMC, Pittsburgh, Pennsylvania, USA13. Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh and UPMC, Pittsburgh, Pennsylvania, USADhiraj Yadav and Claudia M CampbellQ1. What is the natural history and burden of pain in chronic pancreatitis (in relation to treatment)?Abdominal pain is the most frequent symptom of CP. However, the severity, temporal nature, and natural history of pain is highly variable (Quality assessment: moderate, recommendation: strong) While variation in disease estimates exist, the prevalence of CP has been approximated at ~50/100,000 populationADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1053/j.gastro.2013.01.068", "ISSN" : "00165085", "PMID" : "23622135", "abstract" : "Acute pancreatitis is one of the most frequent gastrointestinal causes of hospital admission in the United States. Chronic pancreatitis, although lower in incidence, significantly reduces patients' quality of life. Pancreatic cancer is associated with a high mortality rate and is one of the top 5 causes of death from cancer. The burden of pancreatic disorders is expected to increase over time. The risk and etiology of pancreatitis differ with age and sex, and all pancreatic disorders affect the black population more than any other race. Gallstones are the most common cause of acute pancreatitis, and early cholecystectomy eliminates the risk of future attacks. Alcohol continues to be the single most important risk factor for chronic pancreatitis. Smoking is an independent risk factor for acute and chronic pancreatitis, and its effects could synergize with those of alcohol. Significant risk factors for pancreatic cancer include smoking and non-O blood groups. Alcohol abstinence and smoking cessation can alter the progression of pancreatitis and reduce recurrence; smoking cessation is the most effective strategy to reduce the risk of pancreatic cancer.", "author" : [ { "dropping-particle" : "", "family" : "Yadav", "given" : "Dhiraj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lowenfels", "given" : "Albert B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2013", "5" ] ] }, "note" : "NULL", "page" : "1252-1261", "title" : "The Epidemiology of Pancreatitis and Pancreatic Cancer", "type" : "article-journal", "volume" : "144" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(1)", "plainTextFormattedCitation" : "(1)", "previouslyFormattedCitation" : "(1)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(1). Abdominal pain, alone or during episode(s) of acute pancreatitis, is the most common symptom of CP. Patients typically describe their pain as a dull, sharp or nagging sensation in the upper abdomen, which can radiate to the back, and often presents after or worsened by food intake. In well conducted natural history studies, pain was observed as the initial presentation in ~75% of patientsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0016-5085", "PMID" : "7926511", "abstract" : "BACKGROUND/AIMS Compared with alcoholic pancreatitis, little is known about the natural history of idiopathic pancreatitis. Two hundred forty-nine patients with alcoholic pancreatitis and 66 patients with idiopathic chronic pancreatitis seen at our institution between 1976 and 1982 were investigated. METHODS Records were analyzed retrospectively from the onset of symptomatic disease, and patients were followed up prospectively until 1985. Patients with early-onset (n = 25) and late-onset (n = 41) idiopathic chronic pancreatitis had a median age at onset of symptoms of 19 and 56 years, respectively. RESULTS The gender distribution was nearly equal in idiopathic chronic pancreatitis, but 72% of patients with alcoholic pancreatitis were men (P = 0.001 vs. idiopathic). In early-onset idiopathic pancreatitis, calcification and exocrine and endocrine insufficiency developed more slowly than in late-onset idiopathic and alcoholic pancreatitis (P = 0.03). However, in early idiopathic chronic pancreatitis, pain frequently occurred initially (P = 0.003 vs. late and alcoholic) and was more severe (P = 0.04 vs. late and alcoholic). In late-onset idiopathic pancreatitis, pain was absent in nearly 50% of patients. CONCLUSIONS There are two distinct forms of idiopathic chronic pancreatitis. Patients with early-onset pancreatitis have initially and thereafter a long course of severe pain but slowly develop morphological and functional pancreatic damage, whereas patients with late-onset pancreatitis have a mild and often a painless course. Both forms differ from alcoholic pancreatitis in their equal gender distribution and a much slower rate of calcification.", "author" : [ { "dropping-particle" : "", "family" : "Layer", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamamoto", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kalthoff", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clain", "given" : "J E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bakken", "given" : "L J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "DiMagno", "given" : "E P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "1994", "11" ] ] }, "note" : "NULL", "page" : "1481-7", "title" : "The different courses of early- and late-onset idiopathic and alcoholic chronic pancreatitis.", "type" : "article-journal", "volume" : "107" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(2)", "plainTextFormattedCitation" : "(2)", "previouslyFormattedCitation" : "(2)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(2), and present during the clinical course in 85-97%ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0016-5085", "PMID" : "7926511", "abstract" : "BACKGROUND/AIMS Compared with alcoholic pancreatitis, little is known about the natural history of idiopathic pancreatitis. Two hundred forty-nine patients with alcoholic pancreatitis and 66 patients with idiopathic chronic pancreatitis seen at our institution between 1976 and 1982 were investigated. METHODS Records were analyzed retrospectively from the onset of symptomatic disease, and patients were followed up prospectively until 1985. Patients with early-onset (n = 25) and late-onset (n = 41) idiopathic chronic pancreatitis had a median age at onset of symptoms of 19 and 56 years, respectively. RESULTS The gender distribution was nearly equal in idiopathic chronic pancreatitis, but 72% of patients with alcoholic pancreatitis were men (P = 0.001 vs. idiopathic). In early-onset idiopathic pancreatitis, calcification and exocrine and endocrine insufficiency developed more slowly than in late-onset idiopathic and alcoholic pancreatitis (P = 0.03). However, in early idiopathic chronic pancreatitis, pain frequently occurred initially (P = 0.003 vs. late and alcoholic) and was more severe (P = 0.04 vs. late and alcoholic). In late-onset idiopathic pancreatitis, pain was absent in nearly 50% of patients. CONCLUSIONS There are two distinct forms of idiopathic chronic pancreatitis. Patients with early-onset pancreatitis have initially and thereafter a long course of severe pain but slowly develop morphological and functional pancreatic damage, whereas patients with late-onset pancreatitis have a mild and often a painless course. Both forms differ from alcoholic pancreatitis in their equal gender distribution and a much slower rate of calcification.", "author" : [ { "dropping-particle" : "", "family" : "Layer", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamamoto", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kalthoff", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clain", "given" : "J E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bakken", "given" : "L J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "DiMagno", "given" : "E P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "1994", "11" ] ] }, "note" : "NULL", "page" : "1481-7", "title" : "The different courses of early- and late-onset idiopathic and alcoholic chronic pancreatitis.", "type" : "article-journal", "volume" : "107" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0016-5085", "PMID" : "6706066", "abstract" : "Over the last 20 yr, 245 patients with chronic pancreatitis (163 with alcoholic relapsing pancreatitis; 145 of them with calcific pancreatitis) were prospectively studied at regular intervals with particular regard to pain, pancreatic functions, calcifications, pancreatic surgery, and survival. The median period of observation in the group with alcoholic relapsing calcific pancreatitis was 10.4 yr. In this group of 145 patients, 85% experienced lasting pain relief within a median time of 4.5 yr from onset. A gradual increase of pancreatic calcifications and pancreatic dysfunction was observed with increasing duration of the disease. Pain relief was accompanied by a marked increase in pancreatic dysfunction and calcification. Of 163 patients with alcoholic relapsing pancreatitis, 87 (53%) needed no pancreatic surgery. Seventy-six patients (47%) with recurrent or persistent severe pain, mainly due to pseudocysts (n = 56), underwent either a cyst drainage procedure (n = 22), papillotomy (n = 4), distal pancreatectomy (40%-60%, n = 24), or Wirsungo-jejunostomy (n = 26). The proportion of patients experiencing lasting pain relief was similar in the operated and nonoperated group of patients. In both groups lasting relief from pain was correlated with the duration of the disease and was associated with marked pancreatic dysfunction. The 50% survival time in alcoholic chronic pancreatitis (with or without pancreatic surgery) was 20-24 yr (after onset), thus markedly shorter than in nonalcoholic pancreatitis. Of the 245 patients, 86 died. About 20% of deaths were related to pancreatitis and its complications. Most extrapancreatic causes of death were malignancies, cardiovascular diseases, severe infections, and nonpancreatic surgery.", "author" : [ { "dropping-particle" : "", "family" : "Ammann", "given" : "R W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akovbiantz", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Largiader", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schueler", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-2", "issue" : "5 Pt 1", "issued" : { "date-parts" : [ [ "1984", "5" ] ] }, "note" : "NULL", "page" : "820-8", "title" : "Course and outcome of chronic pancreatitis. Longitudinal study of a mixed medical-surgical series of 245 patients.", "type" : "article-journal", "volume" : "86" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISSN" : "0036-5521", "PMID" : "9754738", "abstract" : "BACKGROUND We investigated the epidemiologic, clinical, and radiologic aspects of a mixed medicosurgical series of chronic pancreatitis patients observed at the University of Verona Centre for the Study of Pancreatic Diseases over the period 1971-1995. METHODS Even though the pathogenesis of chronic pancreatitis has yet to be clarified and the classification is still debatable, the patients were subdivided in accordance with the Marseilles-Rome classification into those with alcoholic, obstructive, familial, and idiopathic forms of the disease. A total of 715 patients were analysed with a median follow-up period of 10 years (range, 1-25 years). RESULTS AND CONCLUSIONS At the end of follow-up the dropout rate amounted to 7.1% (51 patients), and 176 patients (24.6%) had died. Data are reported about the type of chronic pancreatitis, sex, and age distribution at the onset of the disease, drinking and smoking habits before onset and during follow-up, and incidence of calcifications, pain, diabetes, steatorrhoea, and pseudocysts. Surgical aspects, survival curves, and causes of death are also analysed, and the most frequent concomitant diseases in chronic pancreatitis sufferers are discussed.", "author" : [ { "dropping-particle" : "", "family" : "Cavallini", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frulloni", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pederzoli", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Talamini", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bovo", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bassi", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Francesco", "given" : "V", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vaona", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Falconi", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sartori", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Angelini", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brunori", "given" : "M P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Filippini", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of gastroenterology", "id" : "ITEM-3", "issue" : "8", "issued" : { "date-parts" : [ [ "1998", "8" ] ] }, "note" : "NULL", "page" : "880-9", "title" : "Long-term follow-up of patients with chronic pancreatitis in Italy.", "type" : "article-journal", "volume" : "33" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "ISSN" : "0012-2823", "PMID" : "8359556", "abstract" : "The natural course of the classical symptoms of chronic pancreatitis, i.e. pain, exocrine and endocrine pancreatic insufficiency, was followed up in 335 patients over a median of 9.8 years (mean 11.3 +/- 8.3 years). Pain relief was not obtained in the majority of patients, even after a long-term observation of > 10 years, and severe exocrine/endocrine insufficiency, severe duct abnormalities and pancreatic calcifications developed. Alcohol abstinence failed to have a significant beneficial effect on pain. Pancreatic surgery led to pain relief immediately after operation, but later on the pain course between operated and nonoperated patients was not significantly different. Repeated exocrine pancreatic function tests in 143 patients showed that functional exocrine impairment came to a standstill (46%), or improved (11%). At the end of observation, 22% of 335 patients still had normal endocrine function and only 40% required insulin treatment. Alcohol abstinence had a significant beneficial effect on endocrine, but not on exocrine pancreatic insufficiency. Chronic pancreatitis led to a sharp increase in unemployment and retirement. Pancreatic carcinoma occurred in 3% and extrapancreatic carcinoma in 4%. The mortality rate within the observation period was 22%, pancreatitis-induced complications accounted for 13% of these deaths.", "author" : [ { "dropping-particle" : "", "family" : "Lankisch", "given" : "P G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "L\u00f6hr-Happe", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Otto", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Creutzfeldt", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Digestion", "id" : "ITEM-4", "issue" : "3", "issued" : { "date-parts" : [ [ "1993" ] ] }, "note" : "NULL", "page" : "148-55", "title" : "Natural course in chronic pancreatitis. Pain, exocrine and endocrine pancreatic insufficiency and prognosis of the disease.", "type" : "article-journal", "volume" : "54" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(2\u20135)", "plainTextFormattedCitation" : "(2\u20135)", "previouslyFormattedCitation" : "(2\u20135)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(2–5). The prevalence of pain is influenced by demographic factors and etiology. Patients with early onset-disease and those with alcohol etiology are more likely to have pain when compared with patients who have late-onset idiopathic chronic pancreatitisADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0016-5085", "PMID" : "7926511", "abstract" : "BACKGROUND/AIMS Compared with alcoholic pancreatitis, little is known about the natural history of idiopathic pancreatitis. Two hundred forty-nine patients with alcoholic pancreatitis and 66 patients with idiopathic chronic pancreatitis seen at our institution between 1976 and 1982 were investigated. METHODS Records were analyzed retrospectively from the onset of symptomatic disease, and patients were followed up prospectively until 1985. Patients with early-onset (n = 25) and late-onset (n = 41) idiopathic chronic pancreatitis had a median age at onset of symptoms of 19 and 56 years, respectively. RESULTS The gender distribution was nearly equal in idiopathic chronic pancreatitis, but 72% of patients with alcoholic pancreatitis were men (P = 0.001 vs. idiopathic). In early-onset idiopathic pancreatitis, calcification and exocrine and endocrine insufficiency developed more slowly than in late-onset idiopathic and alcoholic pancreatitis (P = 0.03). However, in early idiopathic chronic pancreatitis, pain frequently occurred initially (P = 0.003 vs. late and alcoholic) and was more severe (P = 0.04 vs. late and alcoholic). In late-onset idiopathic pancreatitis, pain was absent in nearly 50% of patients. CONCLUSIONS There are two distinct forms of idiopathic chronic pancreatitis. Patients with early-onset pancreatitis have initially and thereafter a long course of severe pain but slowly develop morphological and functional pancreatic damage, whereas patients with late-onset pancreatitis have a mild and often a painless course. Both forms differ from alcoholic pancreatitis in their equal gender distribution and a much slower rate of calcification.", "author" : [ { "dropping-particle" : "", "family" : "Layer", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamamoto", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kalthoff", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clain", "given" : "J E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bakken", "given" : "L J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "DiMagno", "given" : "E P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "1994", "11" ] ] }, "note" : "NULL", "page" : "1481-7", "title" : "The different courses of early- and late-onset idiopathic and alcoholic chronic pancreatitis.", "type" : "article-journal", "volume" : "107" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0016-5085", "PMID" : "6706066", "abstract" : "Over the last 20 yr, 245 patients with chronic pancreatitis (163 with alcoholic relapsing pancreatitis; 145 of them with calcific pancreatitis) were prospectively studied at regular intervals with particular regard to pain, pancreatic functions, calcifications, pancreatic surgery, and survival. The median period of observation in the group with alcoholic relapsing calcific pancreatitis was 10.4 yr. In this group of 145 patients, 85% experienced lasting pain relief within a median time of 4.5 yr from onset. A gradual increase of pancreatic calcifications and pancreatic dysfunction was observed with increasing duration of the disease. Pain relief was accompanied by a marked increase in pancreatic dysfunction and calcification. Of 163 patients with alcoholic relapsing pancreatitis, 87 (53%) needed no pancreatic surgery. Seventy-six patients (47%) with recurrent or persistent severe pain, mainly due to pseudocysts (n = 56), underwent either a cyst drainage procedure (n = 22), papillotomy (n = 4), distal pancreatectomy (40%-60%, n = 24), or Wirsungo-jejunostomy (n = 26). The proportion of patients experiencing lasting pain relief was similar in the operated and nonoperated group of patients. In both groups lasting relief from pain was correlated with the duration of the disease and was associated with marked pancreatic dysfunction. The 50% survival time in alcoholic chronic pancreatitis (with or without pancreatic surgery) was 20-24 yr (after onset), thus markedly shorter than in nonalcoholic pancreatitis. Of the 245 patients, 86 died. About 20% of deaths were related to pancreatitis and its complications. Most extrapancreatic causes of death were malignancies, cardiovascular diseases, severe infections, and nonpancreatic surgery.", "author" : [ { "dropping-particle" : "", "family" : "Ammann", "given" : "R W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akovbiantz", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Largiader", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schueler", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-2", "issue" : "5 Pt 1", "issued" : { "date-parts" : [ [ "1984", "5" ] ] }, "note" : "NULL", "page" : "820-8", "title" : "Course and outcome of chronic pancreatitis. Longitudinal study of a mixed medical-surgical series of 245 patients.", "type" : "article-journal", "volume" : "86" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(2,3)", "plainTextFormattedCitation" : "(2,3)", "previouslyFormattedCitation" : "(2,3)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(2,3). Pain experience in an individual patient varies widely during the clinical course of disease. For example, in a multicenter cross-sectional study of 518 chronic pancreatitis patients of all etiologies, no, mild-moderate, and severe pain in the preceding year was reported by 15.6%, 17.6% and 66.8% patients respectively. Among patients with pain, 38% reported intermittent pain, and 62% constant pain. Among those with constant pain, only 7% experienced constant severe pain that did not change over timeADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.cgh.2014.10.015", "ISSN" : "1542-7714", "PMID" : "25424572", "abstract" : "BACKGROUND & AIMS Chronic pancreatitis is characterized by inflammation, atrophy, fibrosis with progressive ductal changes, and functional changes that include variable exocrine and endocrine insufficiency and multiple patterns of pain. We investigated whether abdominal imaging features accurately predict patterns of pain. METHODS We collected data from participants in the North American Pancreatitis Study 2 Continuation and Validation, a prospective multicenter study of patients with chronic pancreatitis performed at 13 expert centers in the United States from July 2008 through March 2012. Chronic pancreatitis was defined based on the detection of characteristic changes by cross-sectional abdominal imaging, endoscopic retrograde cholangiopancreatography, endoscopic ultrasonography, or histology analyses. Patients were asked by a physician or trained clinical research coordinator if they had any abdominal pain during the year before enrollment, those who responded \"yes\" were asked to select from a list of 5 pain patterns. By using these patterns, we\u00a0classified patients' pain based on timing and severity. Abnormal pancreatitis-associated features on abdominal imaging were recorded using standardized case report forms. RESULTS Data were collected from 518 patients (mean age, 52 \u00b1 14.6 y; 55% male; and 87.6% white). The most common physician-identified etiologies were alcohol (45.8%) and idiopathic (24.3%); 15.6% of patients reported no abdominal pain in the year before enrollment. The most common individual pain pattern was described as constant mild pain with episodes of severe pain and was reported in 45% of patients. The most common imaging findings included pancreatic ductal dilatation (68%), atrophy (57%), and calcifications (55%). Imaging findings were categorized as obstructive for 20% and as inflammatory for 25% of cases. The distribution of individual imaging findings was similar among patients with different patterns of pain. The distribution of pain patterns did not differ among clinically relevant groups of imaging findings. CONCLUSIONS Mechanisms that determine patterns and severity of pain in patients with chronic pancreatitis are largely independent of structural variants observed by abdominal imaging techniques. Pancreas-relevant quantitative and qualitative pain measures should be included in the evaluation of patients with chronic pancreatitis to assess pain severity independently of imaging findings.", "author" : [ { "dropping-particle" : "", "family" : "Wilcox", "given" : "C Mel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yadav", "given" : "Dhiraj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ye", "given" : "Tian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gardner", "given" : "Timothy B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gelrud", "given" : "Andres", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandhu", "given" : "Bimaljit S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lewis", "given" : "Michele D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Al-Kaade", "given" : "Samer", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cote", "given" : "Gregory A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forsmark", "given" : "Christopher E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guda", "given" : "Nalini M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Conwell", "given" : "Darwin L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banks", "given" : "Peter A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muniraj", "given" : "Thiruvengadam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Romagnuolo", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brand", "given" : "Randall E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slivka", "given" : "Adam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sherman", "given" : "Stuart", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wisniewski", "given" : "Stephen R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Whitcomb", "given" : "David C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anderson", "given" : "Michelle A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2015", "3" ] ] }, "note" : "NULL", "page" : "552-60; quiz e28-9", "title" : "Chronic pancreatitis pain pattern and severity are independent of abdominal imaging findings.", "type" : "article-journal", "volume" : "13" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(6)", "plainTextFormattedCitation" : "(6)", "previouslyFormattedCitation" : "(6)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(6). Interestingly, the duration of disease did not influence the pain experienceADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/gut.2010.213835", "ISSN" : "1468-3288", "PMID" : "21148579", "abstract" : "OBJECTIVE To compare patients with chronic pancreatitis (CP) with constant pain patterns to patients with CP with intermittent pain patterns. METHODS This was a prospective cohort study conducted at 20 tertiary medical centers in the USA comprising 540 subjects with CP. Patients with CP were asked to identify their pain from five pain patterns (A-E) defined by the temporal nature (intermittent or constant) and the severity of the pain (mild, moderate or severe). Pain pattern types were compared with respect to a variety of demographic, quality of life (QOL) and clinical parameters. Rates of disability were the primary outcome. Secondary outcomes included: use of pain medications, days lost from school or work, hospitalisations (preceding year and lifetime) and QOL as measured using the Short Form-12 (SF-12) questionnaire. RESULTS Of the 540 CP patients, 414 patients (77%) self-identified with a particular pain pattern and were analysed. Patients with constant pain, regardless of severity, had higher rates of disability, hospitalisation and pain medication use than patients with intermittent pain. Patients with constant pain had lower QOL (by SF-12) compared with patients who had intermittent pain. Additionally, patients with constant pain were more likely to have alcohol as the aetiology for their pancreatitis. There was no association between the duration of the disease and the quality or severity of the pain. CONCLUSIONS This is the largest study ever conducted of pain in CP. These findings suggest that the temporal nature of pain is a more important determinant of health-related QOL and healthcare utilisation than pain severity. In contrast to previous studies, the pain associated with CP was not found to change in quality over time. These results have important implications for improving our understanding of the mechanisms underlying pain in CP and for the goals of future treatments and interventions.", "author" : [ { "dropping-particle" : "", "family" : "Mullady", "given" : "Daniel K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yadav", "given" : "Dhiraj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Amann", "given" : "Stephen T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Connell", "given" : "Michael R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barmada", "given" : "Michael M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elta", "given" : "Grace H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scheiman", "given" : "James M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wamsteker", "given" : "Erik-Jan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chey", "given" : "William D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Korneffel", "given" : "Meredith L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weinman", "given" : "Beth M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slivka", "given" : "Adam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sherman", "given" : "Stuart", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hawes", "given" : "Robert H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brand", "given" : "Randall E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burton", "given" : "Frank R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lewis", "given" : "Michele D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gardner", "given" : "Timothy B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gelrud", "given" : "Andres", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "DiSario", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baillie", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banks", "given" : "Peter A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Whitcomb", "given" : "David C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anderson", "given" : "Michelle A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "NAPS2 Consortium", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gut", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2011", "1", "1" ] ] }, "page" : "77-84", "title" : "Type of pain, pain-associated complications, quality of life, disability and resource utilisation in chronic pancreatitis: a prospective cohort study.", "type" : "article-journal", "volume" : "60" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(7)", "plainTextFormattedCitation" : "(7)", "previouslyFormattedCitation" : "(7)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(7). During longitudinal follow-up of 207 patients with alcoholic chronic pancreatitis, two patterns of pain were observed – type A and type BADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0016-5085", "PMID" : "10220505", "abstract" : "BACKGROUND & AIMS The pain pattern of chronic pancreatitis (CP) and its surgical implications are discussed. The aim of this study was to (1) define typical pain patterns, (2) correlate pain patterns with the presumptive causes of the pain, and (3) compare the natural history of patients treated conservatively or surgically with respect to pain relief, pancreatic dysfunction, and clinical outcome. METHODS A cohort in this prospective long-term study included 207 patients with alcoholic CP (91 without and 116 with surgery for pain relief). A clinically based staging system was applied to characterize pain in the evolution from onset to end-stage CP. RESULTS Average duration of CP was 17 years. In early-stage CP, episodes of recurrent (acute) pancreatitis predominated. Chronic pain was typically associated with local complications (mainly pseudocysts, 84 of 155; 54%), relieved definitely by a single (drainage) procedure in approximately two thirds of patients. Additional surgery was required for late pain recurrence in 39 patients (34%), primarily symptomatic cholestasis (18 of 39; 46%). All patients achieved complete pain relief in advanced CP. CONCLUSIONS In our experience, relief of chronic pain regularly follows selective surgery tailored to the presumptive pain cause or occurs spontaneously in uncomplicated advanced CP.", "author" : [ { "dropping-particle" : "", "family" : "Ammann", "given" : "R W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muellhaupt", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "1999", "5" ] ] }, "note" : "NULL", "page" : "1132-40", "title" : "The natural history of pain in alcoholic chronic pancreatitis.", "type" : "article-journal", "volume" : "116" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(8)", "plainTextFormattedCitation" : "(8)", "previouslyFormattedCitation" : "(8)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(8). Type A pain was described as episodes, which could last for up to 10 days at a time with pain free intervals lasting up to several months. Type B pain was described as prolonged periods of persistent or recurring pain with no pain free intervals, often requiring repeated hospitalizations. Patients who had only type A pain (44%) were managed medically, while those with type B pain (56%) underwent surgical intervention to achieve pain relief followed by either pain free intervals or a change of pattern to Type A painADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0016-5085", "PMID" : "10220505", "abstract" : "BACKGROUND & AIMS The pain pattern of chronic pancreatitis (CP) and its surgical implications are discussed. The aim of this study was to (1) define typical pain patterns, (2) correlate pain patterns with the presumptive causes of the pain, and (3) compare the natural history of patients treated conservatively or surgically with respect to pain relief, pancreatic dysfunction, and clinical outcome. METHODS A cohort in this prospective long-term study included 207 patients with alcoholic CP (91 without and 116 with surgery for pain relief). A clinically based staging system was applied to characterize pain in the evolution from onset to end-stage CP. RESULTS Average duration of CP was 17 years. In early-stage CP, episodes of recurrent (acute) pancreatitis predominated. Chronic pain was typically associated with local complications (mainly pseudocysts, 84 of 155; 54%), relieved definitely by a single (drainage) procedure in approximately two thirds of patients. Additional surgery was required for late pain recurrence in 39 patients (34%), primarily symptomatic cholestasis (18 of 39; 46%). All patients achieved complete pain relief in advanced CP. CONCLUSIONS In our experience, relief of chronic pain regularly follows selective surgery tailored to the presumptive pain cause or occurs spontaneously in uncomplicated advanced CP.", "author" : [ { "dropping-particle" : "", "family" : "Ammann", "given" : "R W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muellhaupt", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "1999", "5" ] ] }, "note" : "NULL", "page" : "1132-40", "title" : "The natural history of pain in alcoholic chronic pancreatitis.", "type" : "article-journal", "volume" : "116" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(8)", "plainTextFormattedCitation" : "(8)", "previouslyFormattedCitation" : "(8)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(8). A similar empiric analysis has not been conducted in patients with non-alcoholic etiologies, but it is likely that the natural course in these patients also has similar variability in pain patterns during the clinical course. Whether and what fraction of patients achieve a complete and lasting pain-free status during the course of disease remains a matter of debate. According to the burn-out hypothesis, irrespective of the type of treatment received, a majority of patients with chronic pancreatitis achieve lasting pain-free status during the clinical courseADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0016-5085", "PMID" : "6706066", "abstract" : "Over the last 20 yr, 245 patients with chronic pancreatitis (163 with alcoholic relapsing pancreatitis; 145 of them with calcific pancreatitis) were prospectively studied at regular intervals with particular regard to pain, pancreatic functions, calcifications, pancreatic surgery, and survival. The median period of observation in the group with alcoholic relapsing calcific pancreatitis was 10.4 yr. In this group of 145 patients, 85% experienced lasting pain relief within a median time of 4.5 yr from onset. A gradual increase of pancreatic calcifications and pancreatic dysfunction was observed with increasing duration of the disease. Pain relief was accompanied by a marked increase in pancreatic dysfunction and calcification. Of 163 patients with alcoholic relapsing pancreatitis, 87 (53%) needed no pancreatic surgery. Seventy-six patients (47%) with recurrent or persistent severe pain, mainly due to pseudocysts (n = 56), underwent either a cyst drainage procedure (n = 22), papillotomy (n = 4), distal pancreatectomy (40%-60%, n = 24), or Wirsungo-jejunostomy (n = 26). The proportion of patients experiencing lasting pain relief was similar in the operated and nonoperated group of patients. In both groups lasting relief from pain was correlated with the duration of the disease and was associated with marked pancreatic dysfunction. The 50% survival time in alcoholic chronic pancreatitis (with or without pancreatic surgery) was 20-24 yr (after onset), thus markedly shorter than in nonalcoholic pancreatitis. Of the 245 patients, 86 died. About 20% of deaths were related to pancreatitis and its complications. Most extrapancreatic causes of death were malignancies, cardiovascular diseases, severe infections, and nonpancreatic surgery.", "author" : [ { "dropping-particle" : "", "family" : "Ammann", "given" : "R W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akovbiantz", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Largiader", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schueler", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-1", "issue" : "5 Pt 1", "issued" : { "date-parts" : [ [ "1984", "5" ] ] }, "note" : "NULL", "page" : "820-8", "title" : "Course and outcome of chronic pancreatitis. Longitudinal study of a mixed medical-surgical series of 245 patients.", "type" : "article-journal", "volume" : "86" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0016-5085", "PMID" : "10220505", "abstract" : "BACKGROUND & AIMS The pain pattern of chronic pancreatitis (CP) and its surgical implications are discussed. The aim of this study was to (1) define typical pain patterns, (2) correlate pain patterns with the presumptive causes of the pain, and (3) compare the natural history of patients treated conservatively or surgically with respect to pain relief, pancreatic dysfunction, and clinical outcome. METHODS A cohort in this prospective long-term study included 207 patients with alcoholic CP (91 without and 116 with surgery for pain relief). A clinically based staging system was applied to characterize pain in the evolution from onset to end-stage CP. RESULTS Average duration of CP was 17 years. In early-stage CP, episodes of recurrent (acute) pancreatitis predominated. Chronic pain was typically associated with local complications (mainly pseudocysts, 84 of 155; 54%), relieved definitely by a single (drainage) procedure in approximately two thirds of patients. Additional surgery was required for late pain recurrence in 39 patients (34%), primarily symptomatic cholestasis (18 of 39; 46%). All patients achieved complete pain relief in advanced CP. CONCLUSIONS In our experience, relief of chronic pain regularly follows selective surgery tailored to the presumptive pain cause or occurs spontaneously in uncomplicated advanced CP.", "author" : [ { "dropping-particle" : "", "family" : "Ammann", "given" : "R W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muellhaupt", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "1999", "5" ] ] }, "note" : "NULL", "page" : "1132-40", "title" : "The natural history of pain in alcoholic chronic pancreatitis.", "type" : "article-journal", "volume" : "116" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(3,8)", "plainTextFormattedCitation" : "(3,8)", "previouslyFormattedCitation" : "(3,8)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(3,8). This claim, however, has not been substantiated by others, mainly due to persistence of pain symptoms in a significant fraction of patients with ongoing pain even after 10 or more years of diseaseADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0885-3177", "PMID" : "7792289", "abstract" : "The natural course of pain in chronic pancreatitis was followed up in 318 patients over 10.6 +/- 8.0 years (median, 9.0 years). By the end of our follow-up, a significant decline in pain in alcoholics (n = 228) and nonalcoholics (n = 90) (p < 0.001 and p < 0.03) was marred by the fact that, even after more than 10 years, 50% of alcoholics and 62% of nonalcoholics still reported pain attacks (difference insignificant). Only alcoholics had pain relief with increasing exocrine pancreatic insufficiency (p < 0.02), but 54% of alcoholics and 73% of nonalcoholics still had pain attacks despite severe, enzyme substitution-requiring exocrine pancreatic insufficiency. The development of severe endocrine pancreatic insufficiency did not significantly influence the course of pain. It is concluded that no clinically relevant differences exist in the course of pain in alcoholic and nonalcoholic chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Lankisch", "given" : "P G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seidensticker", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "L\u00f6hr-Happe", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Otto", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Creutzfeldt", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreas", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "1995", "5" ] ] }, "note" : "NULL", "page" : "338-41", "title" : "The course of pain is the same in alcohol- and nonalcohol-induced chronic pancreatitis.", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(9)", "plainTextFormattedCitation" : "(9)", "previouslyFormattedCitation" : "(9)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(9). The prevalence of pain seems to decrease with progression of morphological (e.g. calcifications) and functional changes (e.g. endocrine and exocrine insufficiency), however, this does not guarantee a transition to pain-free statusADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0016-5085", "PMID" : "6706066", "abstract" : "Over the last 20 yr, 245 patients with chronic pancreatitis (163 with alcoholic relapsing pancreatitis; 145 of them with calcific pancreatitis) were prospectively studied at regular intervals with particular regard to pain, pancreatic functions, calcifications, pancreatic surgery, and survival. The median period of observation in the group with alcoholic relapsing calcific pancreatitis was 10.4 yr. In this group of 145 patients, 85% experienced lasting pain relief within a median time of 4.5 yr from onset. A gradual increase of pancreatic calcifications and pancreatic dysfunction was observed with increasing duration of the disease. Pain relief was accompanied by a marked increase in pancreatic dysfunction and calcification. Of 163 patients with alcoholic relapsing pancreatitis, 87 (53%) needed no pancreatic surgery. Seventy-six patients (47%) with recurrent or persistent severe pain, mainly due to pseudocysts (n = 56), underwent either a cyst drainage procedure (n = 22), papillotomy (n = 4), distal pancreatectomy (40%-60%, n = 24), or Wirsungo-jejunostomy (n = 26). The proportion of patients experiencing lasting pain relief was similar in the operated and nonoperated group of patients. In both groups lasting relief from pain was correlated with the duration of the disease and was associated with marked pancreatic dysfunction. The 50% survival time in alcoholic chronic pancreatitis (with or without pancreatic surgery) was 20-24 yr (after onset), thus markedly shorter than in nonalcoholic pancreatitis. Of the 245 patients, 86 died. About 20% of deaths were related to pancreatitis and its complications. Most extrapancreatic causes of death were malignancies, cardiovascular diseases, severe infections, and nonpancreatic surgery.", "author" : [ { "dropping-particle" : "", "family" : "Ammann", "given" : "R W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akovbiantz", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Largiader", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schueler", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-1", "issue" : "5 Pt 1", "issued" : { "date-parts" : [ [ "1984", "5" ] ] }, "note" : "NULL", "page" : "820-8", "title" : "Course and outcome of chronic pancreatitis. Longitudinal study of a mixed medical-surgical series of 245 patients.", "type" : "article-journal", "volume" : "86" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0012-2823", "PMID" : "8359556", "abstract" : "The natural course of the classical symptoms of chronic pancreatitis, i.e. pain, exocrine and endocrine pancreatic insufficiency, was followed up in 335 patients over a median of 9.8 years (mean 11.3 +/- 8.3 years). Pain relief was not obtained in the majority of patients, even after a long-term observation of > 10 years, and severe exocrine/endocrine insufficiency, severe duct abnormalities and pancreatic calcifications developed. Alcohol abstinence failed to have a significant beneficial effect on pain. Pancreatic surgery led to pain relief immediately after operation, but later on the pain course between operated and nonoperated patients was not significantly different. Repeated exocrine pancreatic function tests in 143 patients showed that functional exocrine impairment came to a standstill (46%), or improved (11%). At the end of observation, 22% of 335 patients still had normal endocrine function and only 40% required insulin treatment. Alcohol abstinence had a significant beneficial effect on endocrine, but not on exocrine pancreatic insufficiency. Chronic pancreatitis led to a sharp increase in unemployment and retirement. Pancreatic carcinoma occurred in 3% and extrapancreatic carcinoma in 4%. The mortality rate within the observation period was 22%, pancreatitis-induced complications accounted for 13% of these deaths.", "author" : [ { "dropping-particle" : "", "family" : "Lankisch", "given" : "P G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "L\u00f6hr-Happe", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Otto", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Creutzfeldt", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Digestion", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "1993" ] ] }, "note" : "NULL", "page" : "148-55", "title" : "Natural course in chronic pancreatitis. Pain, exocrine and endocrine pancreatic insufficiency and prognosis of the disease.", "type" : "article-journal", "volume" : "54" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISSN" : "0016-5085", "PMID" : "10220505", "abstract" : "BACKGROUND & AIMS The pain pattern of chronic pancreatitis (CP) and its surgical implications are discussed. The aim of this study was to (1) define typical pain patterns, (2) correlate pain patterns with the presumptive causes of the pain, and (3) compare the natural history of patients treated conservatively or surgically with respect to pain relief, pancreatic dysfunction, and clinical outcome. METHODS A cohort in this prospective long-term study included 207 patients with alcoholic CP (91 without and 116 with surgery for pain relief). A clinically based staging system was applied to characterize pain in the evolution from onset to end-stage CP. RESULTS Average duration of CP was 17 years. In early-stage CP, episodes of recurrent (acute) pancreatitis predominated. Chronic pain was typically associated with local complications (mainly pseudocysts, 84 of 155; 54%), relieved definitely by a single (drainage) procedure in approximately two thirds of patients. Additional surgery was required for late pain recurrence in 39 patients (34%), primarily symptomatic cholestasis (18 of 39; 46%). All patients achieved complete pain relief in advanced CP. CONCLUSIONS In our experience, relief of chronic pain regularly follows selective surgery tailored to the presumptive pain cause or occurs spontaneously in uncomplicated advanced CP.", "author" : [ { "dropping-particle" : "", "family" : "Ammann", "given" : "R W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muellhaupt", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-3", "issue" : "5", "issued" : { "date-parts" : [ [ "1999", "5" ] ] }, "note" : "NULL", "page" : "1132-40", "title" : "The natural history of pain in alcoholic chronic pancreatitis.", "type" : "article-journal", "volume" : "116" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(3,5,8)", "plainTextFormattedCitation" : "(3,5,8)", "previouslyFormattedCitation" : "(3,5,8)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(3,5,8). Continued alcohol consumption is linked with disease progressionADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.cgh.2009.08.022", "ISSN" : "1542-7714", "PMID" : "19896091", "abstract" : "This study was undertaken to evaluate the long-term prognosis of acute pancreatitis (AP) in Japan and to identify factors that predict major complications. In 1987, 2533 patients with moderate or severe acute pancreatitis were registered in a national survey in Japan. Follow-up studies were done in 2000 and in 2004 to evaluate recurrence of acute pancreatitis, transition to chronic pancreatitis, development of diabetes mellitus, and mortality. The relationship between incidence of complications and alcohol consumption during follow-up period was also analyzed. Valid replies were obtained from 714 cases in 2000 and 450 cases in 2004. Recurrence of acute pancreatitis occurred in 145 cases, and the recurrence rate was significantly higher in alcoholic pancreatitis compared with other etiologies. A transition to chronic pancreatitis occurred frequently in alcoholic pancreatitis and inversely correlated with existence of pancreatic necrosis in the initial disease. Complication with diabetes mellitus and the transition to chronic pancreatitis strongly correlated with persistent alcohol intake during follow-up period. During the follow-up period, 199 patients died, and 43 died of malignant disease. Recurrence of acute pancreatitis and a transition to chronic pancreatitis frequently occurred in alcoholic pancreatitis. Transition to chronic pancreatitis was inversely correlated with the existence of pancreatic necrosis at the initial presentation. Mortality as a result of malignant disease was not excessive in the patients with history of acute pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Takeyama", "given" : "Yoshifumi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association", "id" : "ITEM-1", "issue" : "11 Suppl", "issued" : { "date-parts" : [ [ "2009", "11" ] ] }, "note" : "NULL", "page" : "S15-7", "title" : "Long-term prognosis of acute pancreatitis in Japan.", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(10)", "plainTextFormattedCitation" : "(10)", "previouslyFormattedCitation" : "(10)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(10), and increases the frequency of pain episodes in patients with established chronic pancreatitisADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0192-0790", "PMID" : "7884174", "abstract" : "To study the role that continuous drinking plays in the pain of chronic pancreatitis, we have examined 67 patients with alcoholic chronic pancreatitis with pain and 29 patients without pain, and we report on their alcoholic habits. Drinking habits played a part 92 (67.6%) of 136 times in patients with pain; in 185 without pain, 86 (46.5%) had continued their drinking habit (p < 0.001). Advanced pancreatic exocrine insufficiency was seen in 27 patients; 11 of them had pain during follow-up, whereas 16 did not. The nondrinker rate was similar in patients with and without pain, whereas among 69 patients with better pancreatic exocrine function, 56 had pain episodes and 13 did not. Alcoholic consumers were significantly more in number in the pain group: 70.4% versus 35% of the no pain group (p < 0.002). Our study shows that drinking alcohol in patients with chronic pancreatitis increased the frequency of painful episodes when there was relatively good pancreatic function, whereas in severe pancreatic insufficiency drinking had less influence on the development of pain.", "author" : [ { "dropping-particle" : "", "family" : "las Heras", "given" : "G", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "la Pe\u00f1a", "given" : "J", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "L\u00f3pez Arias", "given" : "M J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gonzalez-Bernal", "given" : "A C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mart\u00edn-Ramos", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pons-Romero", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of clinical gastroenterology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "1995", "1" ] ] }, "note" : "NULL", "page" : "33-6", "title" : "Drinking habits and pain in chronic pancreatitis.", "type" : "article-journal", "volume" : "20" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(11)", "plainTextFormattedCitation" : "(11)", "previouslyFormattedCitation" : "(11)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(11). Although no empiric data specifically associates tobacco smoking to the pain experience, given the role of tobacco in disease progressionADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/mpa.0b013e31812e965e", "ISSN" : "1536-4828", "PMID" : "18090237", "abstract" : "OBJECTIVE Cigarette smoking is associated with a higher risk of developing chronic pancreatitis (CP) and increases the likelihood of developing pancreatic calcifications. The aim of this study was to know whether smoking cessation modifies the course of the disease. METHODS Patients with CP who had been followed up for more than 6 years from clinical onset and who had not developed calcifications after 5 years were analyzed. We studied smokers, never-smokers, and patients who had given up smoking within 5 years. For actuarial analysis, the sixth year was considered as time 0. RESULTS Of the 360 patients, there were 43 women and 317 men (88.1%) with a mean age of 38.7 years. The median follow-up was 19.0 years. Chronic pancreatitis was alcohol-associated in 255 patients, hereditary in 10, obstructive in 54, and idiopathic in 41. There were 317 smokers (88.1%) and 259 alcohol drinkers (71.9%). At the end of the follow-up, 212 patients (59.8%) developed calcifications. Concerning the risk of calcifications, never-smokers and ex-smokers had similar actuarial curves, and these were significantly different from the curve for smokers (P < 0.003). Considering never-smokers as the reference class, ex-smokers had an odds ratio (OR) of 0.56 (95.0% confidence interval [CI], 0.2-1.4; P = not significant), patients smoking 1 to 10 cigarettes per day had an OR of 1.95 (95.0% CI, 1.1-3.4; P < 0.019), patients smoking 11 to 20 cigarettes per day had an OR of 1.76 (95.0% CI, 1.1-2.8; P < 0.0018), and those smoking more than 20 cigarettes per day had an OR of 1.79 (95.0% CI, 1.1-2.9; P < 0.019). Alcohol cessation seems to have no influence. CONCLUSIONS Smoking cessation in the first years from the clinical onset of CP reduces the risk of developing pancreatic calcifications.", "author" : [ { "dropping-particle" : "", "family" : "Talamini", "given" : "Giorgio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bassi", "given" : "Claudio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Falconi", "given" : "Massimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sartori", "given" : "Nora", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vaona", "given" : "Bruna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bovo", "given" : "Paolo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benini", "given" : "Luigi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cavallini", "given" : "Giorgio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pederzoli", "given" : "Paolo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vantini", "given" : "Italo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreas", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2007", "11" ] ] }, "note" : "NULL", "page" : "320-6", "title" : "Smoking cessation at the clinical onset of chronic pancreatitis and risk of pancreatic calcifications.", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(12)", "plainTextFormattedCitation" : "(12)", "previouslyFormattedCitation" : "(12)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(12), it is conceivable that it may have an indirect and negative effect on pain.The underlying mechanisms responsible for producing pain in chronic pancreatitis are unclear. Pain could be related to status of the pancreas (e.g. acute or chronic inflammation, pancreatic ductal obstruction from stones and/or stricture), peripancreatic structures (e.g. common bile duct stricture, gastric outlet or duodenal obstruction) or local complications (e.g. pseudocyst). In a subset, no obvious structural cause is apparent. Similar to other pain conditions, little association exists between pain report and morphological characteristics in chronic pancreatitis patientsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.cgh.2014.10.015", "ISSN" : "1542-7714", "PMID" : "25424572", "abstract" : "BACKGROUND & AIMS Chronic pancreatitis is characterized by inflammation, atrophy, fibrosis with progressive ductal changes, and functional changes that include variable exocrine and endocrine insufficiency and multiple patterns of pain. We investigated whether abdominal imaging features accurately predict patterns of pain. METHODS We collected data from participants in the North American Pancreatitis Study 2 Continuation and Validation, a prospective multicenter study of patients with chronic pancreatitis performed at 13 expert centers in the United States from July 2008 through March 2012. Chronic pancreatitis was defined based on the detection of characteristic changes by cross-sectional abdominal imaging, endoscopic retrograde cholangiopancreatography, endoscopic ultrasonography, or histology analyses. Patients were asked by a physician or trained clinical research coordinator if they had any abdominal pain during the year before enrollment, those who responded \"yes\" were asked to select from a list of 5 pain patterns. By using these patterns, we\u00a0classified patients' pain based on timing and severity. Abnormal pancreatitis-associated features on abdominal imaging were recorded using standardized case report forms. RESULTS Data were collected from 518 patients (mean age, 52 \u00b1 14.6 y; 55% male; and 87.6% white). The most common physician-identified etiologies were alcohol (45.8%) and idiopathic (24.3%); 15.6% of patients reported no abdominal pain in the year before enrollment. The most common individual pain pattern was described as constant mild pain with episodes of severe pain and was reported in 45% of patients. The most common imaging findings included pancreatic ductal dilatation (68%), atrophy (57%), and calcifications (55%). Imaging findings were categorized as obstructive for 20% and as inflammatory for 25% of cases. The distribution of individual imaging findings was similar among patients with different patterns of pain. The distribution of pain patterns did not differ among clinically relevant groups of imaging findings. CONCLUSIONS Mechanisms that determine patterns and severity of pain in patients with chronic pancreatitis are largely independent of structural variants observed by abdominal imaging techniques. Pancreas-relevant quantitative and qualitative pain measures should be included in the evaluation of patients with chronic pancreatitis to assess pain severity independently of imaging findings.", "author" : [ { "dropping-particle" : "", "family" : "Wilcox", "given" : "C Mel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yadav", "given" : "Dhiraj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ye", "given" : "Tian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gardner", "given" : "Timothy B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gelrud", "given" : "Andres", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandhu", "given" : "Bimaljit S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lewis", "given" : "Michele D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Al-Kaade", "given" : "Samer", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cote", "given" : "Gregory A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forsmark", "given" : "Christopher E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guda", "given" : "Nalini M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Conwell", "given" : "Darwin L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banks", "given" : "Peter A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muniraj", "given" : "Thiruvengadam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Romagnuolo", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brand", "given" : "Randall E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slivka", "given" : "Adam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sherman", "given" : "Stuart", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wisniewski", "given" : "Stephen R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Whitcomb", "given" : "David C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anderson", "given" : "Michelle A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2015", "3" ] ] }, "note" : "NULL", "page" : "552-60; quiz e28-9", "title" : "Chronic pancreatitis pain pattern and severity are independent of abdominal imaging findings.", "type" : "article-journal", "volume" : "13" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(6)", "plainTextFormattedCitation" : "(6)", "previouslyFormattedCitation" : "(6)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(6). Thus, other factors clearly play a role in individual patient’s pain experience. Studies to systematically evaluate risk factors for the development of pain and examination of pain course and patterns are warranted. Such work may lead to the formulation of novel treatments that could potentially be deployed proactively to intervene for patients suffering with painful chronic pancreatitis.Naturally, CP is a major burden for the patients and it is regarded the most severe complication to the disease. Accordingly, both pain intensity and the frequency of pain attacks have been shown to reduce life quality in patients with CPADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/gut.2010.213835", "ISSN" : "1468-3288", "PMID" : "21148579", "abstract" : "OBJECTIVE To compare patients with chronic pancreatitis (CP) with constant pain patterns to patients with CP with intermittent pain patterns. METHODS This was a prospective cohort study conducted at 20 tertiary medical centers in the USA comprising 540 subjects with CP. Patients with CP were asked to identify their pain from five pain patterns (A-E) defined by the temporal nature (intermittent or constant) and the severity of the pain (mild, moderate or severe). Pain pattern types were compared with respect to a variety of demographic, quality of life (QOL) and clinical parameters. Rates of disability were the primary outcome. Secondary outcomes included: use of pain medications, days lost from school or work, hospitalisations (preceding year and lifetime) and QOL as measured using the Short Form-12 (SF-12) questionnaire. RESULTS Of the 540 CP patients, 414 patients (77%) self-identified with a particular pain pattern and were analysed. Patients with constant pain, regardless of severity, had higher rates of disability, hospitalisation and pain medication use than patients with intermittent pain. Patients with constant pain had lower QOL (by SF-12) compared with patients who had intermittent pain. Additionally, patients with constant pain were more likely to have alcohol as the aetiology for their pancreatitis. There was no association between the duration of the disease and the quality or severity of the pain. CONCLUSIONS This is the largest study ever conducted of pain in CP. These findings suggest that the temporal nature of pain is a more important determinant of health-related QOL and healthcare utilisation than pain severity. In contrast to previous studies, the pain associated with CP was not found to change in quality over time. These results have important implications for improving our understanding of the mechanisms underlying pain in CP and for the goals of future treatments and interventions.", "author" : [ { "dropping-particle" : "", "family" : "Mullady", "given" : "Daniel K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yadav", "given" : "Dhiraj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Amann", "given" : "Stephen T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Connell", "given" : "Michael R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barmada", "given" : "Michael M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elta", "given" : "Grace H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scheiman", "given" : "James M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wamsteker", "given" : "Erik-Jan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chey", "given" : "William D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Korneffel", "given" : "Meredith L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weinman", "given" : "Beth M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slivka", "given" : "Adam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sherman", "given" : "Stuart", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hawes", "given" : "Robert H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brand", "given" : "Randall E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burton", "given" : "Frank R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lewis", "given" : "Michele D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gardner", "given" : "Timothy B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gelrud", "given" : "Andres", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "DiSario", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baillie", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banks", "given" : "Peter A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Whitcomb", "given" : "David C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anderson", "given" : "Michelle A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "NAPS2 Consortium", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gut", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2011", "1", "1" ] ] }, "page" : "77-84", "title" : "Type of pain, pain-associated complications, quality of life, disability and resource utilisation in chronic pancreatitis: a prospective cohort study.", "type" : "article-journal", "volume" : "60" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.pan.2014.09.009", "ISSN" : "1424-3911", "PMID" : "25455540", "abstract" : "BACKGROUND/OBJECTIVES Chronic pancreatitis (CP) is a disabling disease characterised by abdominal pain, and various pancreatic and extra-pancreatic complications. We investigated the interactions between pain characteristics (i.e. pain severity and its pattern in time), complications, and quality of life (QOL) in patients with CP. METHODS This was a cross-sectional study of 106 patients with CP conducted at two North European tertiary medical centres. Detailed information on clinical patient characteristics was obtained from interviews and through review of the individual patient records. Pain severity scores and pain pattern time profiles were extracted from the modified brief pain inventory short form and correlated to QOL as assessed by the EORTC QLQ-C30 questionnaire. Interactions with exocrine and endocrine pancreatic insufficiency, as well as pancreatic and extra-pancreatic complications were analysed using regression models. RESULTS Pain was the most prominent symptom in our cohort and its severity was significantly correlated with EORTC global health status (r = -0.46; P < 0.001) and most functional and symptom subscales. In contrast the patterns of pain in time were not associated with any of the life quality subscales. When controlling for interactions from exocrine and endocrine pancreatic insufficiency no effect modifications were evident (P = 0.72 and P = 0.85 respectively), while the presence of pancreatic and extra-pancreatic complications was associated with an almost 15% decrease in life quality (P = 0.004). CONCLUSIONS Pain severity and disease related complications significantly reduce life quality in patients with CP. This information is important in order to design more accurate and clinical meaningful endpoints in future outcome trials.", "author" : [ { "dropping-particle" : "", "family" : "Olesen", "given" : "S\u00f8ren Schou", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Juel", "given" : "Jacob", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nielsen", "given" : "Anders Klitgaard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fr\u00f8kj\u00e6r", "given" : "Jens Br\u00f8ndum", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "Oliver H G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn Mohr", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2014", "11" ] ] }, "note" : "NULL", "page" : "497-502", "title" : "Pain severity reduces life quality in chronic pancreatitis: Implications for design of future outcome trials.", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(7,13)", "plainTextFormattedCitation" : "(7,13)", "previouslyFormattedCitation" : "(7,13)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(7,13). A recent large study, using SF12 questionnaire, found pain to be the single most important predictor of quality of life in CP. When compared with patients with no pain, those with constant pain had a 5 (in the absence of severe pain) or 10-point (in the presence of severe pain) reduction in physical, and 7-point reduction in mental quality of life (a difference of 3 or more points is clinically relevant) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ajg.2017.42", "ISSN" : "1572-0241", "PMID" : "28244497", "abstract" : "OBJECTIVES Chronic pancreatitis (CP) has a profound independent effect on quality of life (QOL). Our aim was to identify factors that impact the QOL in CP patients. METHODS We used data on 1,024 CP patients enrolled in the three NAPS2 studies. Information on demographics, risk factors, co-morbidities, disease phenotype, and treatments was obtained from responses to structured questionnaires. Physical and mental component summary (PCS and MCS, respectively) scores generated using responses to the Short Form-12 (SF-12) survey were used to assess QOL at enrollment. Multivariable linear regression models determined independent predictors of QOL. RESULTS Mean PCS and MCS scores were 36.7\u00b111.7 and 42.4\u00b112.2, respectively. Significant (P<0.05) negative impact on PCS scores in multivariable analyses was noted owing to constant mild-moderate pain with episodes of severe pain or constant severe pain (10 points), constant mild-moderate pain (5.2), pain-related disability/unemployment (5.1), current smoking (2.9 points), and medical co-morbidities. Significant (P<0.05) negative impact on MCS scores was related to constant pain irrespective of severity (6.8-6.9 points), current smoking (3.9 points), and pain-related disability/unemployment (2.4 points). In women, disability/unemployment resulted in an additional 3.7 point reduction in MCS score. Final multivariable models explained 27% and 18% of the variance in PCS and MCS scores, respectively. Etiology, disease duration, pancreatic morphology, diabetes, exocrine insufficiency, and prior endotherapy/pancreatic surgery had no significant independent effect on QOL. CONCLUSIONS Constant pain, pain-related disability/unemployment, current smoking, and concurrent co-morbidities significantly affect the QOL in CP. Further research is needed to identify factors impacting QOL not explained by our analyses.", "author" : [ { "dropping-particle" : "", "family" : "Machicado", "given" : "Jorge D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Amann", "given" : "Stephen T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anderson", "given" : "Michelle A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abberbock", "given" : "Judah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sherman", "given" : "Stuart", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Conwell", "given" : "Darwin L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cote", "given" : "Gregory A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Vikesh K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lewis", "given" : "Michele D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alkaade", "given" : "Samer", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandhu", "given" : "Bimaljit S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guda", "given" : "Nalini M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muniraj", "given" : "Thiruvengadam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tang", "given" : "Gong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baillie", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brand", "given" : "Randall E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gardner", "given" : "Timothy B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gelrud", "given" : "Andres", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forsmark", "given" : "Christopher E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banks", "given" : "Peter A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slivka", "given" : "Adam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilcox", "given" : "C Mel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Whitcomb", "given" : "David C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yadav", "given" : "Dhiraj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American journal of gastroenterology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2017", "4", "28" ] ] }, "page" : "633-642", "title" : "Quality of Life in Chronic Pancreatitis is Determined by Constant Pain, Disability/Unemployment, Current Smoking, and Associated Co-Morbidities.", "type" : "article-journal", "volume" : "112" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(14)", "plainTextFormattedCitation" : "(14)", "previouslyFormattedCitation" : "(14)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(14). Pankaj Jay Pasricha, S?ren Schou Olesen and Eva SzigethyQ2. Are there different types of pain in CP and what does it mean for treatment?Pain in CP remains poorly understood and inadequately correlated with neurobiological mechanisms. By definition, CP is characterized by inflammation but unlike other inflammatory disorders, there is a paucity of therapeutic attempts targeting this particular aspect of pathophysiology. On the other hand, there are striking changes in structure and function in both the peripheral and central nervous system in this condition, lending plausibility to a maladaptive state that includes both neuropathic and dysfunctional pain. In the absence of effective anti-inflammatory approaches, it is clearly important to focus on the alteration of function that accompanies these changes in the nociceptive system as a potential therapeutic target. (Quality assessment: low; Recommendation: strong; Agreement: strong) Pain in chronic pancreatitis is difficult to manage for multiple reasons as described several times in this position paper. A significant factor in this regard is the heterogeneous and multiplex nature of pain, representing different drivers (anatomical, inflammatory, primary neurobiological, psychosocial), locations (peripheral, central), and confounding factors (pharmacological dependence and aggravation). This chapter will attempt to provide a classification based on the etiopathogenesis of pain in the hope that it will provide the basis of more rational approach to treatment. General biological categories of painAs reviewed by Woolf, pain can be classified broadly in terms of utility to the living being as either being adaptive/protective or maladaptive/pathologicalADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1172/JCI45178", "ISSN" : "1558-8238", "PMID" : "21041955", "abstract" : "To paraphrase Cole Porter's famous 1926 song, \"What is this thing called pain? This funny thing called pain, just who can solve its mystery?\" Pain, like love, is all consuming: when you have it, not much else matters, and there is nothing you can do about it. Unlike love, however, we are actually beginning to tease apart the mystery of pain. The substantial progress made over the last decade in revealing the genes, molecules, cells, and circuits that determine the sensation of pain offers new opportunities to manage it, as revealed in this Review series by some of the foremost experts in the field.", "author" : [ { "dropping-particle" : "", "family" : "Woolf", "given" : "Clifford J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of clinical investigation", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2010", "11", "1" ] ] }, "note" : "NULL", "page" : "3742-4", "title" : "What is this thing called pain?", "type" : "article-journal", "volume" : "120" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(15)", "plainTextFormattedCitation" : "(15)", "previouslyFormattedCitation" : "(15)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(15). Adaptive pain serves the organism by helping it to avoid harm from environmental or internal insults. Thus pain in response to a prick or contact with a hot object warns us of the possibility of serious injury and is the purest manifestation of the “nociceptive” response. In the clinical context, the most common form of pain can also be considered adaptive occurring in response to tissue injury of various origins (mechanical, chemical, infectious, immunological etc.), with accompanying inflammation that results in hypersensitivity (sensitization) of the nociceptive system. Such a pain is also adaptive in that it either results in seeking attention for it or causes avoidance of physical contact/movement that could interfere with healing and/or aggravate the injury. The other broad category of pain can be considered maladaptive, in that it does not serve a useful purpose, as it is no longer linked to ongoing injury or pain in the relevant tissue. Instead, the pain is believed to result from either damage (neuropathy) or dysfunction to the nociceptive system itself, which is now behaving “pathologically” (hence the name). Clinical patterns of pain in chronic pancreatitis An early approach to classifying pain in chronic alcoholic pancreatitis was made by Amman et al based on the clinical pattern in a cohort of 207 patients followed prospectively with both surgical and conservative managementADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0016-5085", "PMID" : "10220505", "abstract" : "BACKGROUND & AIMS The pain pattern of chronic pancreatitis (CP) and its surgical implications are discussed. The aim of this study was to (1) define typical pain patterns, (2) correlate pain patterns with the presumptive causes of the pain, and (3) compare the natural history of patients treated conservatively or surgically with respect to pain relief, pancreatic dysfunction, and clinical outcome. METHODS A cohort in this prospective long-term study included 207 patients with alcoholic CP (91 without and 116 with surgery for pain relief). A clinically based staging system was applied to characterize pain in the evolution from onset to end-stage CP. RESULTS Average duration of CP was 17 years. In early-stage CP, episodes of recurrent (acute) pancreatitis predominated. Chronic pain was typically associated with local complications (mainly pseudocysts, 84 of 155; 54%), relieved definitely by a single (drainage) procedure in approximately two thirds of patients. Additional surgery was required for late pain recurrence in 39 patients (34%), primarily symptomatic cholestasis (18 of 39; 46%). All patients achieved complete pain relief in advanced CP. CONCLUSIONS In our experience, relief of chronic pain regularly follows selective surgery tailored to the presumptive pain cause or occurs spontaneously in uncomplicated advanced CP.", "author" : [ { "dropping-particle" : "", "family" : "Ammann", "given" : "R W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muellhaupt", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "1999", "5" ] ] }, "note" : "NULL", "page" : "1132-40", "title" : "The natural history of pain in alcoholic chronic pancreatitis.", "type" : "article-journal", "volume" : "116" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(8)", "plainTextFormattedCitation" : "(8)", "previouslyFormattedCitation" : "(8)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(8). “A-type pain” pattern, with one or more discrete episodes of pain interspersed with pain-free intervals of several months to years, was observed in all patients in their series. Slightly less than half (44%) of patients also had “B-type pain” described as persistent (i.e. daily) pain over prolonged periods of time and/or closely clustered exacerbations of severe pain, with the typical case having severe pain 2 or more days per week for at least 2 months and requiring repeated hospitalizations in most instances. A more recent study by the North American Pancreatic Study (NAPS) group also studied a prospectively followed cohort of 414 patients of mixed etiology (nearly half of whom were thought to be alcoholic in etiology) and attempted to classify pain according to temporal and severity criteria, and correlate these with quality of life, resource utilization and pain-associated complicationsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/gut.2010.213835", "ISSN" : "1468-3288", "PMID" : "21148579", "abstract" : "OBJECTIVE To compare patients with chronic pancreatitis (CP) with constant pain patterns to patients with CP with intermittent pain patterns. METHODS This was a prospective cohort study conducted at 20 tertiary medical centers in the USA comprising 540 subjects with CP. Patients with CP were asked to identify their pain from five pain patterns (A-E) defined by the temporal nature (intermittent or constant) and the severity of the pain (mild, moderate or severe). Pain pattern types were compared with respect to a variety of demographic, quality of life (QOL) and clinical parameters. Rates of disability were the primary outcome. Secondary outcomes included: use of pain medications, days lost from school or work, hospitalisations (preceding year and lifetime) and QOL as measured using the Short Form-12 (SF-12) questionnaire. RESULTS Of the 540 CP patients, 414 patients (77%) self-identified with a particular pain pattern and were analysed. Patients with constant pain, regardless of severity, had higher rates of disability, hospitalisation and pain medication use than patients with intermittent pain. Patients with constant pain had lower QOL (by SF-12) compared with patients who had intermittent pain. Additionally, patients with constant pain were more likely to have alcohol as the aetiology for their pancreatitis. There was no association between the duration of the disease and the quality or severity of the pain. CONCLUSIONS This is the largest study ever conducted of pain in CP. These findings suggest that the temporal nature of pain is a more important determinant of health-related QOL and healthcare utilisation than pain severity. In contrast to previous studies, the pain associated with CP was not found to change in quality over time. These results have important implications for improving our understanding of the mechanisms underlying pain in CP and for the goals of future treatments and interventions.", "author" : [ { "dropping-particle" : "", "family" : "Mullady", "given" : "Daniel K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yadav", "given" : "Dhiraj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Amann", "given" : "Stephen T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Connell", "given" : "Michael R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barmada", "given" : "Michael M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elta", "given" : "Grace H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scheiman", "given" : "James M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wamsteker", "given" : "Erik-Jan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chey", "given" : "William D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Korneffel", "given" : "Meredith L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weinman", "given" : "Beth M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slivka", "given" : "Adam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sherman", "given" : "Stuart", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hawes", "given" : "Robert H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brand", "given" : "Randall E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burton", "given" : "Frank R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lewis", "given" : "Michele D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gardner", "given" : "Timothy B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gelrud", "given" : "Andres", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "DiSario", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baillie", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banks", "given" : "Peter A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Whitcomb", "given" : "David C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anderson", "given" : "Michelle A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "NAPS2 Consortium", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gut", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2011", "1", "1" ] ] }, "page" : "77-84", "title" : "Type of pain, pain-associated complications, quality of life, disability and resource utilisation in chronic pancreatitis: a prospective cohort study.", "type" : "article-journal", "volume" : "60" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(7)", "plainTextFormattedCitation" : "(7)", "previouslyFormattedCitation" : "(7)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(7). Although their parsing of pain categories was more nuanced, it appears that alcohol, tobacco use as well as most meaningful clinical outcomes including quality of life were best predicted when “intermittent” (about 45% of patients) versus “constant” pain were compared, thus echoing the earlier binary classification. However, it should be pointed out the descriptions in these two papers are not strictly comparable: the NAPS2 data is more based on patient recall of their pain pattern at a single time point whereas the study by Amman et al gathered this information by longitudinal observation of their patients.Pattern of pain CP and correspondence with putative neurobiological causesInflammatory PainIt is intuitively appealing to suggest that a significant, if not major, type of pain in CP is inflammatory in nature, whether or not associated with mechanical/space-occupying lesions such as ductal dilation or pseudocysts. However, a more rigorous analysis would require consideration of the following issues before coming to a final conclusion:Biological plausibility. Dolor (pain) is a cardinal feature of inflammation and the biological and clinical evidence linking the two is incontrovertible in general. The development of animal models to study pain in CP has also shown that inflammatory pain in CP is mechanistically generally similar to other chronic inflammatory conditions. The expression of numerous algogenic factors is altered in experimental models as well as in human pancreatic specimens obtained from patients with CP upon surgery. These molecules include NGF and its high affinity receptor (TrkA)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0017-5749", "PMID" : "10940282", "abstract" : "BACKGROUND Changes in substance P content and a relationship between the degree of perineural inflammation and pain has been demonstrated in chronic pancreatitis. Whether a relationship exists between neural alteration and pancreatic inflammation (neurogenic inflammation) is not known. AIMS In the present study we evaluated gene expression of preprotachykinin A (PPT-A), the gene encoding substance P, and interleukin 8, a proinflammatory and hyperalgesic mediator whose release is co-regulated by substance P. PATIENTS Pancreatic tissue specimens obtained from 21 patients (16 male, five female) with chronic pancreatitis and 18 healthy organ donors (nine male, nine female) were analysed. METHODS Gene expression of PPT-A and interleukin 8 was studied by northern blot analysis. Respective proteins were localised using immunohistochemistry. RESULTS Northern blot analysis showed that PTT-A mRNA expression levels were present at comparable levels in normal and chronic pancreatitis tissue samples. In contrast, interleukin 8 mRNA was expressed at very low levels in normal controls but was increased 41-fold (p<0. 001) in chronic pancreatitis tissue samples. Using immunohistochemistry, interleukin 8 protein was localised mainly in immune cells often found around enlarged pancreatic nerves. In addition, in chronic pancreatitis, intense interleukin 8 immunostaining was present in metaplastic ductal cells of the atrophic pancreatic parenchyma. In chronic pancreatitis samples there was a positive relationship between interleukin 8 mRNA levels and the presence of ductal metaplasia (r=0.795; p<0.001) and the inflammation score (r=0.713; p<0.001). CONCLUSIONS Our data indicate that in chronic pancreatitis, the increase in substance P in enlarged pancreatic nerves is not caused by enhanced intrapancreatic PTT-A mRNA expression, suggesting that the location of substance P synthesis is outside of the pancreas. In addition, localisation of interleukin 8 positive immune cells around pancreatic nerves further supports the existence of neuroimmune interactions as a pathophysiological mechanism in chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Sebastiano", "given" : "P", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mola", "given" : "F F", "non-dropping-particle" : "di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Febbo", "given" : "C", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baccante", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Porreca", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Innocenti", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Friess", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "B\u00fcchler", "given" : "M W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gut", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2000", "9" ] ] }, "note" : "NULL", "page" : "423-8", "title" : "Expression of interleukin 8 (IL-8) and substance P in human chronic pancreatitis.", "type" : "article-journal", "volume" : "47" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0003-4932", "PMID" : "10561084", "abstract" : "OBJECTIVE To study the mechanisms that are involved in nerve growth and contribute to pain generation in chronic pancreatitis (CP). SUMMARY BACKGROUND DATA Chronic pancreatitis is a painful disease associated with characteristic nerve changes, including an increase in nerve number and diameter. The mechanisms that influence nerve growth are not known. Nerve growth factor (NGF) and its high-affinity tyrosine kinase receptor A (TrkA) are involved in neural development and survival and growth of central and peripheral nerves. METHODS Nerve growth factor and TrkA were investigated by Northern blot analysis, in situ hybridization, and immunohistochemical staining in the pancreases of 24 patients with CP, and the findings were correlated with clinical parameters. RESULTS By Northern blot analysis, NGF and TrkA mRNA expression were increased in 42% (13.1-fold) and 54% (5.5-fold) of the CP samples (p < 0.01), respectively. In situ hybridization revealed that in CP, enhanced NGF mRNA expression was present in metaplastic ductal cells, in degenerating acinar cells, and in acinar cells dedifferentiating into tubular structures. TrkA mRNA was intensely present in the perineurium. Further, enhanced NGF and TrkA mRNA signals were also present in intrapancreatic ganglia cells in CP samples. Immunohistochemistry confirmed the in situ hybridization findings. Analysis of the molecular findings with clinical parameters revealed a significant relation (p < 0.05) between NGF mRNA levels and pancreatic fibrosis (r = 0.64) and acinar cell damage (r = 0.74) and between TrkA mRNA and pain intensity (r = 0.84). CONCLUSION Activation of the NGF/TrkA pathway occurs in CP. It might influence neural morphologic changes and the pain syndrome in this disorder.", "author" : [ { "dropping-particle" : "", "family" : "Friess", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhu", "given" : "Z W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mola", "given" : "F F", "non-dropping-particle" : "di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kulli", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graber", "given" : "H U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andren-Sandberg", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zimmermann", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Korc", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reinshagen", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "B\u00fcchler", "given" : "M W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of surgery", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "1999", "11" ] ] }, "note" : "NULL", "page" : "615-24", "title" : "Nerve growth factor and its high-affinity receptor in chronic pancreatitis.", "type" : "article-journal", "volume" : "230" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(16,17)", "plainTextFormattedCitation" : "(16,17)", "previouslyFormattedCitation" : "(16,17)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(16,17), TRPV1ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/gut.2005.073205", "ISSN" : "0017-5749", "PMID" : "16174661", "abstract" : "BACKGROUND Success of chemotherapy and alleviation of pain are frequently less than optimal in pancreatic cancer patients, leading to increasing interest in new pharmacological substances, such as vanilloids. Our study addressed the question of whether vanilloids influence pancreatic cancer cell growth, and if vanilloids could be used for pain treatment via the vanilloid 1 receptor (VR1) in pancreatic cancer patients. METHODS In vitro, the effect of resiniferatoxin (vanilloid analogue) on apoptosis and cell growth in pancreatic cancer cells--either alone, combined with 5-fluorouracil (5-FU), or combined with gemcitabine--was determined by annexin V staining, FACS analysis, and MTT assay, respectively. VR1 expression was evaluated on RNA and protein level by quantitative polymerase chain reaction and immunohistochemistry in human pancreatic cancer and chronic pancreatitis. Patient characteristics--especially pain levels--were registered in a prospective database and correlated with VR1 expression. RESULTS Resiniferatoxin induced apoptosis by targeting mitochondrial respiration and decreased cell growth in pancreatic cancer cells without showing synergistic effects with 5-FU or gemcitabine. Expression of VR1 was significantly upregulated in human pancreatic cancer and chronic pancreatitis. VR1 expression was related to the intensity of pain reported by cancer patients but not to the intensity of pain reported by patients with chronic pancreatitis. CONCLUSIONS Resiniferatoxin induced apoptosis in pancreatic cancer cells indicates that vanilloids may be useful in the treatment of human pancreatic cancer. Furthermore, vanilloid might be a novel and effective treatment option for neurogenic pain in patients with pancreatic cancer.", "author" : [ { "dropping-particle" : "", "family" : "Hartel", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mola", "given" : "F F", "non-dropping-particle" : "di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Selvaggi", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mascetta", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wente", "given" : "M N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Felix", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giese", "given" : "N A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hinz", "given" : "U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sebastiano", "given" : "P", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "B\u00fcchler", "given" : "M W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Friess", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gut", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2006", "4", "1" ] ] }, "note" : "NULL", "page" : "519-28", "title" : "Vanilloids in pancreatic cancer: potential for chemotherapy and pain management.", "type" : "article-journal", "volume" : "55" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(18)", "plainTextFormattedCitation" : "(18)", "previouslyFormattedCitation" : "(18)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(18), as well as SP and its receptor, NK-1ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0017-5749", "PMID" : "10940282", "abstract" : "BACKGROUND Changes in substance P content and a relationship between the degree of perineural inflammation and pain has been demonstrated in chronic pancreatitis. Whether a relationship exists between neural alteration and pancreatic inflammation (neurogenic inflammation) is not known. AIMS In the present study we evaluated gene expression of preprotachykinin A (PPT-A), the gene encoding substance P, and interleukin 8, a proinflammatory and hyperalgesic mediator whose release is co-regulated by substance P. PATIENTS Pancreatic tissue specimens obtained from 21 patients (16 male, five female) with chronic pancreatitis and 18 healthy organ donors (nine male, nine female) were analysed. METHODS Gene expression of PPT-A and interleukin 8 was studied by northern blot analysis. Respective proteins were localised using immunohistochemistry. RESULTS Northern blot analysis showed that PTT-A mRNA expression levels were present at comparable levels in normal and chronic pancreatitis tissue samples. In contrast, interleukin 8 mRNA was expressed at very low levels in normal controls but was increased 41-fold (p<0. 001) in chronic pancreatitis tissue samples. Using immunohistochemistry, interleukin 8 protein was localised mainly in immune cells often found around enlarged pancreatic nerves. In addition, in chronic pancreatitis, intense interleukin 8 immunostaining was present in metaplastic ductal cells of the atrophic pancreatic parenchyma. In chronic pancreatitis samples there was a positive relationship between interleukin 8 mRNA levels and the presence of ductal metaplasia (r=0.795; p<0.001) and the inflammation score (r=0.713; p<0.001). CONCLUSIONS Our data indicate that in chronic pancreatitis, the increase in substance P in enlarged pancreatic nerves is not caused by enhanced intrapancreatic PTT-A mRNA expression, suggesting that the location of substance P synthesis is outside of the pancreas. In addition, localisation of interleukin 8 positive immune cells around pancreatic nerves further supports the existence of neuroimmune interactions as a pathophysiological mechanism in chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Sebastiano", "given" : "P", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mola", "given" : "F F", "non-dropping-particle" : "di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Febbo", "given" : "C", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baccante", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Porreca", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Innocenti", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Friess", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "B\u00fcchler", "given" : "M W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gut", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2000", "9" ] ] }, "note" : "NULL", "page" : "423-8", "title" : "Expression of interleukin 8 (IL-8) and substance P in human chronic pancreatitis.", "type" : "article-journal", "volume" : "47" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0885-3177", "PMID" : "1372738", "abstract" : "We sought to identify characteristics of peptidergic innervation that altered in patients with chronic pancreatitis. Pancreatic tissue removed from patients with chronic pancreatitis was analyzed by immunohistochemistry using antisera against neuropeptide Y, tyrosine hydroxylase, vasoactive intestinal polypeptide, peptide histidine isoleucine, calcitonin gene-related peptide, and substance P, respectively. In accordance with recent findings, the number and diameter of intralobular and interlobular nerve bundles were found to be increased as compared with control pancreas from organ donors. The striking change in the peptidergic innervation pattern in chronic pancreatitis concerned these altered nerves. It consisted of an intensification of the immunostaining for calcitonin gene-related peptide and substance P in numerous fibers contained in these nerves. Adjacent sections showed that immunoreactive substance P and immunoreactive calcitonin gene-related peptide coexisted in these fibers. Because both of these peptides are generally regarded as pain transmitter candidates, our findings provide further evidence that changes in pancreatic nerves themselves might be responsible for the long-lasting pain syndrome in chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "B\u00fcchler", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weihe", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Friess", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Malfertheiner", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bockman", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "M\u00fcller", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nohr", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beger", "given" : "H G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreas", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "1992" ] ] }, "note" : "NULL", "page" : "183-92", "title" : "Changes in peptidergic innervation in chronic pancreatitis.", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISSN" : "0304-3959", "PMID" : "11275376", "abstract" : "Recent theories of pathogenesis of pain in chronic pancreatitis (CP) are neuroimmune interactions of intrapancreatic nerves and inflammatory cells and increase in levels of pain neurotransmitters such as substance P (SP). This study analyzed the expression and localization of neurokinin 1 receptor (NK-1R), which binds SP, and its association with pain and inflammation in CP. Pancreatic tissues from 31 patients (22 males, nine females; mean age 45.9+/-9.4 years) with CP were evaluated. Nine normal pancreases (five males, four females; mean age 42.9+/-9.5 years) served as controls. Quantitative PCR was used to determine the NK-1R mRNA expression levels and in situ hybridization and immunohistochemistry were used to localize expression sites of NK-1R mRNA and protein, respectively. We also analyzed whether an association exists between NK-1R mRNA expression and pain and inflammation. In CP samples, in situ hybridization and immunohistochemistry localized NK-1R mRNA expression and protein mainly in the nerves, ganglia, blood vessels, inflammatory cells and occasionally in fibroblasts. In patients with mild to moderate and strong intensity of pain, NK-1R mRNA levels were increased 14- and 30-fold over controls, respectively. There was a significant relationship between NK-1R mRNA levels and intensity of pain (r=0.46, P=0.03), NK-1R mRNA and the frequency of pain (r=0.51, P=0.04), and NK-1 mRNA and duration of pain (r=0.46, P=0.01) in CP patients, but not with the degree of tissue inflammation. NK-1R signaling may be involved in the pain syndrome of CP. The expression of NK-1R in inflammatory cells and blood vessels also points to an interaction of immunoreactive substance P nerves, inflammatory cells and blood vessels, and further supports the existence of a neuroimmune interaction that probably influences the pain syndrome and chronic inflammatory changes so characteristic of CP.", "author" : [ { "dropping-particle" : "V", "family" : "Shrikhande", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Friess", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mola", "given" : "F F", "non-dropping-particle" : "di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tempia-Caliera", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Conejo Garcia", "given" : "J R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhu", "given" : "Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zimmermann", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "B\u00fcchler", "given" : "M W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pain", "id" : "ITEM-3", "issue" : "3", "issued" : { "date-parts" : [ [ "2001", "4" ] ] }, "note" : "NULL", "page" : "209-17", "title" : "NK-1 receptor gene expression is related to pain in chronic pancreatitis.", "type" : "article-journal", "volume" : "91" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(16,19,20)", "plainTextFormattedCitation" : "(16,19,20)", "previouslyFormattedCitation" : "(16,19,20)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(16,19,20), CGRPADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0885-3177", "PMID" : "1372738", "abstract" : "We sought to identify characteristics of peptidergic innervation that altered in patients with chronic pancreatitis. Pancreatic tissue removed from patients with chronic pancreatitis was analyzed by immunohistochemistry using antisera against neuropeptide Y, tyrosine hydroxylase, vasoactive intestinal polypeptide, peptide histidine isoleucine, calcitonin gene-related peptide, and substance P, respectively. In accordance with recent findings, the number and diameter of intralobular and interlobular nerve bundles were found to be increased as compared with control pancreas from organ donors. The striking change in the peptidergic innervation pattern in chronic pancreatitis concerned these altered nerves. It consisted of an intensification of the immunostaining for calcitonin gene-related peptide and substance P in numerous fibers contained in these nerves. Adjacent sections showed that immunoreactive substance P and immunoreactive calcitonin gene-related peptide coexisted in these fibers. Because both of these peptides are generally regarded as pain transmitter candidates, our findings provide further evidence that changes in pancreatic nerves themselves might be responsible for the long-lasting pain syndrome in chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "B\u00fcchler", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weihe", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Friess", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Malfertheiner", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bockman", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "M\u00fcller", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nohr", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beger", "given" : "H G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreas", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "1992" ] ] }, "note" : "NULL", "page" : "183-92", "title" : "Changes in peptidergic innervation in chronic pancreatitis.", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(19)", "plainTextFormattedCitation" : "(19)", "previouslyFormattedCitation" : "(19)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(19), BDNFADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0163-2116", "PMID" : "11508661", "abstract" : "Our purpose was to investigate brain-derived neurotrophic factor (BDNF) in chronic pancreatitis (CP) in comparison with the normal pancreas and to evaluate its association with pain. By immunohistochemistry, in the normal pancreas BDNF immunoreactivity was moderately present in the cytoplasm of most ductal cells and weakly present in most acinar cells, islet cells, nerve fibers (including perineurium), and ganglia cells. In contrast, in CP intense immunostaining of BDNF was present in most cells of ductular complexes and in the perineurium of enlarged nerves. Moderate immunostaining of BDNF was found in degenerating acinar cells and islet cells. In addition, moderate immunoreactivity of BDNF was also detected in most enlarged nerve fibers and intrinsic pancreatic ganglia cells in CP samples. Western blot analysis also revealed 5.6-fold higher BDNF levels in CP samples (P < 0.01) compared with normal pancreas samples. The expression level of BDNF was positively correlated with pain intensity (P < 0.01) and pain frequency (P < 0.01) of CP patients. Furthermore, there was a significant relationship (r = 0.68, P < 0.01) between the BDNF immunostaining and the global pain scores. BDNF is increased in CP. Its association with pain suggests that it functions as a peripheral and central pain modulator, as reported previously in other inflammatory disorders.", "author" : [ { "dropping-particle" : "", "family" : "Zhu", "given" : "Z W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Friess", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zimmermann", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "B\u00fcchler", "given" : "M W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Digestive diseases and sciences", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2001", "8" ] ] }, "note" : "NULL", "page" : "1633-9", "title" : "Brain-derived neurotrophic factor (BDNF) is upregulated and associated with pain in chronic pancreatitis.", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(21)", "plainTextFormattedCitation" : "(21)", "previouslyFormattedCitation" : "(21)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(21) as well as other neurotrophic factors such as artemin and its receptor GFR3ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/gut.2006.105528", "ISSN" : "0017-5749", "PMID" : "17047099", "abstract" : "BACKGROUND AND AIMS Chronic pancreatitis is characterised by severe abdominal neuropathic pain, perineural inflammatory cell infiltrations and intrapancreatic neural growth. Artemin was recently shown to eliminate neuropathic pain and reverse neurochemical damage after nerve injury. The role of artemin and its receptor GFRalpha3 was investigated in patients with chronic pancreatitis. METHODS Expression of artemin and its receptor GFRalpha3 was studied in chronic pancreatitis (n = 66) and normal (n = 22) pancreatic tissues by quantitative reverse transcription-polymerase chain reaction (QRT-PCR) and western blot analysis. Artemin expression was correlated with pain and pathomorphological changes (inflammation, perineural inflammatory cell infiltration, neural alterations and fibrosis). Immunohistochemistry was used to localise artemin and GFRalpha3 in the tissues. To detect sources of artemin, primary human pancreatic stellate cells (hPSCs) were isolated and analysed by QRT-PCR and immunocytology analysis. RESULTS In chronic pancreatitis, artemin and GFRalpha3 were significantly overexpressed and located in smooth muscle cells of arteries, Schwann cells and neural ganglia. Increased levels of artemin mRNA correlated with pain severity, inflammation, perineural inflammatory cell infiltration, neural density and hypertrophy. Furthermore, the severity of fibrosis was positively related with artemin expression and neural alterations. Activated hPSCs expressed low basal levels of artemin mRNA which were upregulated by exposure to transforming growth factor (TGF)beta1. CONCLUSIONS Overexpression of artemin in chronic pancreatitis might function as a compensatory upregulation in order to repair neural damage incurred by ongoing pancreatic inflammation. Upregulation of TGFbeta1 seems not only to increase pancreatic fibrosis but also to contribute to neural alteration by stimulating artemin expression in hPSCs. However, overexpression of endogenous artemin does not seem to be sufficient to prevent pain in chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Ceyhan", "given" : "G\u00fcralp O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergmann", "given" : "Frank", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kadihasanoglu", "given" : "Mustafa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erkan", "given" : "Mert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Park", "given" : "Weon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hinz", "given" : "Ulf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giese", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "M\u00fcller", "given" : "Michael W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "B\u00fcchler", "given" : "Markus W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giese", "given" : "Nathalia A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Friess", "given" : "Helmut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gut", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2007", "4", "1" ] ] }, "note" : "NULL", "page" : "534-44", "title" : "The neurotrophic factor artemin influences the extent of neural damage and growth in chronic pancreatitis.", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(22)", "plainTextFormattedCitation" : "(22)", "previouslyFormattedCitation" : "(22)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(22). Elevated levels of PGE2 have recently been found in the pancreatic secretions of patients with early CP who have significant pain but no clear structural abnormalitiesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ctg.2014.23", "ISSN" : "2155-384X", "PMID" : "25630864", "abstract" : "OBJECTIVES Chronic pancreatitis (CP) may be difficult to diagnose in early stages. We aimed to measure pancreatic juice (PJ) prostaglandin E2 (PGE2) concentrations to determine whether they are elevated in CP and improve diagnosis of early disease. METHODS We measured PJ PGE2 in 10 patients with established CP, 25 patients who met criteria for \"minimal change\" chronic pancreatitis (MCCP), and 10 normal control participants. RESULTS Median PJ PGE2 was elevated in CP (307\u2009pg/ml, IQR (249-362)) and MCCP (568\u2009pg/ml, (418-854)) compared with normal controls (104\u2009pg/ml, (68-206)) (P\u2264 0.001). Area under receiving operator curve (AUROC) for diagnosis of CP and MCCP was 0.9 and 0.62, respectively, for PJ bicarbonate concentration alone; AUROC was 1.0 and 0.94 for the combination of PJ bicarbonate and PGE2 concentrations. CONCLUSIONS PJ PGE2 appears to be a biomarker for CP and is elevated in both established and \"minimal change\" chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Abu Dayyeh", "given" : "Barham K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Conwell", "given" : "Darwin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buttar", "given" : "Navtej S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kadilaya", "given" : "Vivek", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hart", "given" : "Philip A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baumann", "given" : "Nikola A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bick", "given" : "Benjamin L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chari", "given" : "Suresh T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chowdhary", "given" : "Sonia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clain", "given" : "Jonathan E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gleeson", "given" : "Ferga C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Linda S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Levy", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pearson", "given" : "Randall K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Petersen", "given" : "Bret T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rajan", "given" : "Elizabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steen", "given" : "Hanno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suleiman", "given" : "Shadeah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banks", "given" : "Peter A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vege", "given" : "Santhi S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Topazian", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical and translational gastroenterology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2015", "1", "29" ] ] }, "note" : "NULL", "page" : "e72", "title" : "Pancreatic juice prostaglandin e2 concentrations are elevated in chronic pancreatitis and improve detection of early disease.", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(23)", "plainTextFormattedCitation" : "(23)", "previouslyFormattedCitation" : "(23)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(23). Some but not all of these have been shown to correlate with pain severity (also see below), although causation is not proven. Nevertheless, these studies have been very valuable in supporting and strengthening evolving theories on the neural pathogenesis of pain in chronic pancreatitis, in keeping with what we have learnt from animal modelsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nrgastro.2011.274", "ISBN" : "1759-5053 (Electronic) 1759-5045 (Linking)", "ISSN" : "1759-5053", "PMID" : "22269952", "abstract" : "Chronic pancreatitis is typically a painful condition and it can be associated with a severe burden of disease. The pathogenesis of pain in this disorder is poorly understood and its treatment has been largely empirical, often consisting of surgical or other invasive methods, with an outcome that is variable and frequently unsatisfactory. Human and experimental studies have indicated a critical role for neuronal mechanisms that result in peripheral and central sensitization. The pancreatic nociceptor seems to be significantly affected in this condition, with increased excitability associated with downregulation of potassium currents. Some of the specific molecules implicated in this process include the vanilloid receptor, TRPV1, nerve growth factor, the protease activated receptor 2 and a variety of others that are discussed in this Review. Studies have also indicated novel therapeutic targets for this condition.", "author" : [ { "dropping-particle" : "", "family" : "Pasricha", "given" : "Pankaj Jay", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jay", "given" : "Pankaj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature reviews. Gastroenterology & hepatology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2012", "1", "24" ] ] }, "page" : "140-51", "publisher" : "Nature Publishing Group", "title" : "Unraveling the mystery of pain in chronic pancreatitis.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(24)", "plainTextFormattedCitation" : "(24)", "previouslyFormattedCitation" : "(24)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(24). Coincidence between inflammatory and painful exacerbations in time. If this was true, it would follow that the “intermittent” episodes of pain observed in patients correspond to a “flare” of inflammation. Many of these patients are hospitalized for “pancreatitis” during such episodes so such a connection is certainly plausible, although the literature does not actually provide evidence of correlation with established biomarkers of inflammation. With persistent pain patterns, the association with inflammation is even more controversial. In their paper, Amman et al state that, type B pain was thought to most often result from a potentially correctible cause - pseudocysts (54%), obstructive cholestasis (24%) and “presumptive ductal hypertension” (14%), with prompt relief by a drainage procedureADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0016-5085", "PMID" : "10220505", "abstract" : "BACKGROUND & AIMS The pain pattern of chronic pancreatitis (CP) and its surgical implications are discussed. The aim of this study was to (1) define typical pain patterns, (2) correlate pain patterns with the presumptive causes of the pain, and (3) compare the natural history of patients treated conservatively or surgically with respect to pain relief, pancreatic dysfunction, and clinical outcome. METHODS A cohort in this prospective long-term study included 207 patients with alcoholic CP (91 without and 116 with surgery for pain relief). A clinically based staging system was applied to characterize pain in the evolution from onset to end-stage CP. RESULTS Average duration of CP was 17 years. In early-stage CP, episodes of recurrent (acute) pancreatitis predominated. Chronic pain was typically associated with local complications (mainly pseudocysts, 84 of 155; 54%), relieved definitely by a single (drainage) procedure in approximately two thirds of patients. Additional surgery was required for late pain recurrence in 39 patients (34%), primarily symptomatic cholestasis (18 of 39; 46%). All patients achieved complete pain relief in advanced CP. CONCLUSIONS In our experience, relief of chronic pain regularly follows selective surgery tailored to the presumptive pain cause or occurs spontaneously in uncomplicated advanced CP.", "author" : [ { "dropping-particle" : "", "family" : "Ammann", "given" : "R W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muellhaupt", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "1999", "5" ] ] }, "note" : "NULL", "page" : "1132-40", "title" : "The natural history of pain in alcoholic chronic pancreatitis.", "type" : "article-journal", "volume" : "116" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(8)", "plainTextFormattedCitation" : "(8)", "previouslyFormattedCitation" : "(8)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(8). However, these results probably reflected the surgical bias in their series, as they have not been borne out by others. In a large prospective cohort study conducted by the NAPS2 consortium, there was no correlation between temporal pattern and the presence or absence of radiological evidence of inflammation or obstructive pathology. Indeed, many patients with CP but no pain had similar findings than those with painADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/gut.2010.213835", "ISSN" : "1468-3288", "PMID" : "21148579", "abstract" : "OBJECTIVE To compare patients with chronic pancreatitis (CP) with constant pain patterns to patients with CP with intermittent pain patterns. METHODS This was a prospective cohort study conducted at 20 tertiary medical centers in the USA comprising 540 subjects with CP. Patients with CP were asked to identify their pain from five pain patterns (A-E) defined by the temporal nature (intermittent or constant) and the severity of the pain (mild, moderate or severe). Pain pattern types were compared with respect to a variety of demographic, quality of life (QOL) and clinical parameters. Rates of disability were the primary outcome. Secondary outcomes included: use of pain medications, days lost from school or work, hospitalisations (preceding year and lifetime) and QOL as measured using the Short Form-12 (SF-12) questionnaire. RESULTS Of the 540 CP patients, 414 patients (77%) self-identified with a particular pain pattern and were analysed. Patients with constant pain, regardless of severity, had higher rates of disability, hospitalisation and pain medication use than patients with intermittent pain. Patients with constant pain had lower QOL (by SF-12) compared with patients who had intermittent pain. Additionally, patients with constant pain were more likely to have alcohol as the aetiology for their pancreatitis. There was no association between the duration of the disease and the quality or severity of the pain. CONCLUSIONS This is the largest study ever conducted of pain in CP. These findings suggest that the temporal nature of pain is a more important determinant of health-related QOL and healthcare utilisation than pain severity. In contrast to previous studies, the pain associated with CP was not found to change in quality over time. These results have important implications for improving our understanding of the mechanisms underlying pain in CP and for the goals of future treatments and interventions.", "author" : [ { "dropping-particle" : "", "family" : "Mullady", "given" : "Daniel K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yadav", "given" : "Dhiraj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Amann", "given" : "Stephen T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Connell", "given" : "Michael R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barmada", "given" : "Michael M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elta", "given" : "Grace H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scheiman", "given" : "James M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wamsteker", "given" : "Erik-Jan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chey", "given" : "William D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Korneffel", "given" : "Meredith L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weinman", "given" : "Beth M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slivka", "given" : "Adam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sherman", "given" : "Stuart", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hawes", "given" : "Robert H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brand", "given" : "Randall E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burton", "given" : "Frank R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lewis", "given" : "Michele D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gardner", "given" : "Timothy B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gelrud", "given" : "Andres", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "DiSario", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baillie", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banks", "given" : "Peter A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Whitcomb", "given" : "David C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anderson", "given" : "Michelle A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "NAPS2 Consortium", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gut", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2011", "1", "1" ] ] }, "page" : "77-84", "title" : "Type of pain, pain-associated complications, quality of life, disability and resource utilisation in chronic pancreatitis: a prospective cohort study.", "type" : "article-journal", "volume" : "60" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(7)", "plainTextFormattedCitation" : "(7)", "previouslyFormattedCitation" : "(7)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(7). Correlation between severity of inflammation and painThere are two lines of evidence on this subject, with seemingly conflicting results. The first comes from careful histological examination of pancreatic specimens from patients with CP showing correlation between the expression of several inflammatory biomarkers or cell types with pain. Immune cells are abundantly found in CP and their products including cytokines such as IL-8 and chemokines such as fractalkine are strongly implicated in neural responses and correlate with pain intensity in humansADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0016-5085", "PMID" : "9136844", "abstract" : "BACKGROUND & AIMS Changes in innervation pattern and neuropeptide content have been shown in chronic pancreatitis (CP), including increased neuronal expression of growth-associated protein 43 (GAP-43). We used GAP-43 as an established marker of neuronal plasticity and correlated histological findings with pain scores of patients with CP. METHODS In tissue samples from 29 patients with CP, the parenchyma-fibrosis ratio, degree of perineural immune cell infiltration, and neuronal GAP-43 immunoreactivity were determined by digitized morphometry and correlated with individual pain scores. RESULTS In CP, GAP-43 was significantly increased in pancreatic nerve fibers and intrinsic neurons. GAP-43 expression correlated with individual pain scores. The infiltration of pancreatic nerves by immune cells was significantly correlated with the intensity of pain. Pain scores correlated neither with the degree of pancreatic fibrosis nor with the duration of the disease. CONCLUSIONS The results suggest that infiltration of pancreatic nerves by immune cells and neuronal plasticity are pathogenic factors for the generation of pain, whereas the degree of pancreatic fibrosis has no major impact on pain in CP.", "author" : [ { "dropping-particle" : "", "family" : "Sebastiano", "given" : "P", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fink", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weihe", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Friess", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Innocenti", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beger", "given" : "H G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "B\u00fcchler", "given" : "M W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "1997", "5" ] ] }, "note" : "NULL", "page" : "1648-55", "title" : "Immune cell infiltration and growth-associated protein 43 expression correlate with pain in chronic pancreatitis.", "type" : "article-journal", "volume" : "112" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1038/labinvest.2008.170", "ISSN" : "1530-0307", "PMID" : "19153557", "abstract" : "The chemokine fractalkine induces migration of inflammatory cells into inflamed tissues, thereby aggravating inflammatory tissue damage and fibrosis. Furthermore, fractalkine increases neuropathic pain through glial activation, which can be diminished by blocking of its receptor, CX3CR1, through neutralizing antibodies. As chronic pancreatitis (CP) is characterized by tissue infiltration of inflammatory cells, fibrosis, pancreatic neuritis and severe pain, the roles of fractalkine and CX3CR1 were investigated in CP (n=61) and normal pancreas (NP, n=21) by QRT-PCR, western blot and immunohistochemistry analyses. Their expression correlated with the severity of pancreatic neuritis, fibrosis, intrapancreatic nerve fiber density and hypertrophy, pain, CP duration and with the amount of inflammatory cell infiltrate immuno-positive for CD45 and CD68. To investigate the influence of fractalkine on pancreatic fibrogenesis, human pancreatic stellate cells (hPSCs) were isolated from patients with CP, incubated with fractalkine and then Collagen-1 and alpha-smooth muscle actin (alpha-SMA) expressions were measured. CX3CR1, but not fractalkine, mRNA was overexpressed in CP. In contrast, the protein levels of both CX3CR1 and fractalkine were upregulated. Neuro-immunoreactivity for fractalkine and CX3CR1 was strongest in patients suffering from severe pain and pancreatic neuritis. Long-term suffering from CP was noticeably related to increased neural immunoreactivity of fractalkine. Furthermore, fractalkine and CX3CR1 mRNA overexpressions were associated with enhanced lymphocyte and macrophage infiltration. Advanced fibrosis was associated with increased fractalkine expression, whereas in vitro fractalkine had no significant impact on collagen-1 and alpha-SMA expressions in hPSCs. Therefore, pancreatic fractalkine expression appears to be linked to visceral pain and to the recruitment of inflammatory cells into the pancreatic tissue and nerve fibers, with subsequent pancreatic neuritis. However, pancreatic fibrogenesis is probably indirectly influenced by fractalkine. Taken together, these novel findings suggest that CX3CR1 represents a potential novel therapeutic target to reduce inflammation and modulate pain in CP.", "author" : [ { "dropping-particle" : "", "family" : "Ceyhan", "given" : "G\u00fcralp O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deucker", "given" : "Stefanie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Demir", "given" : "Ihsan Ekin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erkan", "given" : "Mert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schmelz", "given" : "Martin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergmann", "given" : "Frank", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "M\u00fcller", "given" : "Michael W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giese", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "B\u00fcchler", "given" : "Markus W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giese", "given" : "Nathalia A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Friess", "given" : "Helmut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Laboratory investigation; a journal of technical methods and pathology", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2009", "3", "19" ] ] }, "note" : "NULL", "page" : "347-61", "title" : "Neural fractalkine expression is closely linked to pain and pancreatic neuritis in human chronic pancreatitis.", "type" : "article-journal", "volume" : "89" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(25,26)", "plainTextFormattedCitation" : "(25,26)", "previouslyFormattedCitation" : "(25,26)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(25,26). Mast cells are also increased in chronic pancreatitis in humansADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0046-8177", "PMID" : "11727255", "abstract" : "Chronic pancreatitis (CP) is characterized by mononuclear inflammatory cell infiltration and replacement of the destroyed parenchyma by fibrous tissue. Recently, mast cells have been implicated in chronic inflammatory processes with fibrous tissue deposition. Therefore, the number and distribution of mast cells and their state of activation were evaluated in 12 normal specimens and in 46 specimens of CP with different causes (alcoholic, tropical, and idiopathic). Furthermore, the presence of stem cell factor (SCF), the main mast cell growth factor, and of its receptor, c-kit, was also assessed. In CP tissues, mast cells were localized both in the fibrotic areas and in the residual acinar parenchyma. The total number of mast cells was significantly higher in CP than in the normal pancreas (P < .0001) and correlated positively with the extent of fibrosis and the intensity of inflammation. Immunoglobulin E (IgE)-dependent mast cell activation was higher in CP than in the normal pancreas. No differences in mast cell number or IgE positivity were found among the 3 causes of CP. SCF-and c-kit immunoreactive mast cells were mostly localized in fibrous tissue and around regenerating ducts, which were also positive for c-kit but were negative for SCF. These results suggest that mast cells, activated by an IgE-dependent mechanism and/or by an SCF-c-kit autocrine loop, are a relevant component of the inflammatory infiltrate in CP, independent of the underlying cause. Their localization near degenerating acini and regenerating ducts might indicate that they play a crucial role in tissue destruction and remodeling in CP.", "author" : [ { "dropping-particle" : "", "family" : "Esposito", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Friess", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kappeler", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shrikhande", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kleeff", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramesh", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zimmermann", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "B\u00fcchler", "given" : "M W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Human pathology", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2001", "11" ] ] }, "note" : "NULL", "page" : "1174-83", "title" : "Mast cell distribution and activation in chronic pancreatitis.", "type" : "article-journal", "volume" : "32" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(27)", "plainTextFormattedCitation" : "(27)", "previouslyFormattedCitation" : "(27)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(27) and patients with painful CP demonstrated a 3.5-fold increase in pancreatic mast cells as compared with those with painless CPADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1186/1471-230X-5-8", "ISSN" : "1471-230X", "PMID" : "15745445", "abstract" : "BACKGROUND The biological basis of pain in chronic pancreatitis is poorly understood. Mast cells have been implicated in the pathogenesis of pain in other conditions. We hypothesized that mast cells play a role in the pain of chronic pancreatitis. We examined the association of pain with mast cells in autopsy specimens of patients with painful chronic pancreatitis. We explored our hypothesis further using an experimental model of trinitrobenzene sulfonic acid (TNBS) -induced chronic pancreatitis in both wild type (WT) and mast cell deficient mice (MCDM). METHODS Archival tissues with histological diagnoses of chronic pancreatitis were identified and clinical records reviewed for presence or absence of reported pain in humans. Mast cells were counted. The presence of pain was assessed using von Frey Filaments (VFF) to measure abdominal withdrawal responses in both WT and MCDM mice with and without chronic pancreatitis. RESULTS Humans with painful chronic pancreatitis demonstrated a 3.5-fold increase in pancreatic mast cells as compared with those with painless chronic pancreatitis.WT mice with chronic pancreatitis were significantly more sensitive as assessed by VFF pain testing of the abdomen when compared with MCDM. CONCLUSION Humans with painful chronic pancreatitis have an increased number of pancreatic mast cells as compared with those with painless chronic pancreatitis. MCDM are less sensitive to mechanical stimulation of the abdomen after induction of chronic pancreatitis as compared with WT. Mast cells may play an important role in the pathogenesis of pain in chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Hoogerwerf", "given" : "Willemijntje A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gondesen", "given" : "Kelly", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xiao", "given" : "Shu-Yuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Winston", "given" : "John H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Willis", "given" : "William D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pasricha", "given" : "Pankaj J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMC gastroenterology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2005", "3", "3" ] ] }, "note" : "NULL", "page" : "8", "title" : "The role of mast cells in the pathogenesis of pain in chronic pancreatitis.", "type" : "article-journal", "volume" : "5" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(28)", "plainTextFormattedCitation" : "(28)", "previouslyFormattedCitation" : "(28)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(28). On the other hand, and in contrast to the earlier studies by Amman et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0016-5085", "PMID" : "10220505", "abstract" : "BACKGROUND & AIMS The pain pattern of chronic pancreatitis (CP) and its surgical implications are discussed. The aim of this study was to (1) define typical pain patterns, (2) correlate pain patterns with the presumptive causes of the pain, and (3) compare the natural history of patients treated conservatively or surgically with respect to pain relief, pancreatic dysfunction, and clinical outcome. METHODS A cohort in this prospective long-term study included 207 patients with alcoholic CP (91 without and 116 with surgery for pain relief). A clinically based staging system was applied to characterize pain in the evolution from onset to end-stage CP. RESULTS Average duration of CP was 17 years. In early-stage CP, episodes of recurrent (acute) pancreatitis predominated. Chronic pain was typically associated with local complications (mainly pseudocysts, 84 of 155; 54%), relieved definitely by a single (drainage) procedure in approximately two thirds of patients. Additional surgery was required for late pain recurrence in 39 patients (34%), primarily symptomatic cholestasis (18 of 39; 46%). All patients achieved complete pain relief in advanced CP. CONCLUSIONS In our experience, relief of chronic pain regularly follows selective surgery tailored to the presumptive pain cause or occurs spontaneously in uncomplicated advanced CP.", "author" : [ { "dropping-particle" : "", "family" : "Ammann", "given" : "R W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muellhaupt", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "1999", "5" ] ] }, "note" : "NULL", "page" : "1132-40", "title" : "The natural history of pain in alcoholic chronic pancreatitis.", "type" : "article-journal", "volume" : "116" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(8)", "plainTextFormattedCitation" : "(8)", "previouslyFormattedCitation" : "(8)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(8), the largest prospective study to date using modern radiological techniques found no evidence that either pain severity or temporal pattern correlates with inflammatory changes on imagingADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.cgh.2014.10.015", "ISSN" : "1542-7714", "PMID" : "25424572", "abstract" : "BACKGROUND & AIMS Chronic pancreatitis is characterized by inflammation, atrophy, fibrosis with progressive ductal changes, and functional changes that include variable exocrine and endocrine insufficiency and multiple patterns of pain. We investigated whether abdominal imaging features accurately predict patterns of pain. METHODS We collected data from participants in the North American Pancreatitis Study 2 Continuation and Validation, a prospective multicenter study of patients with chronic pancreatitis performed at 13 expert centers in the United States from July 2008 through March 2012. Chronic pancreatitis was defined based on the detection of characteristic changes by cross-sectional abdominal imaging, endoscopic retrograde cholangiopancreatography, endoscopic ultrasonography, or histology analyses. Patients were asked by a physician or trained clinical research coordinator if they had any abdominal pain during the year before enrollment, those who responded \"yes\" were asked to select from a list of 5 pain patterns. By using these patterns, we\u00a0classified patients' pain based on timing and severity. Abnormal pancreatitis-associated features on abdominal imaging were recorded using standardized case report forms. RESULTS Data were collected from 518 patients (mean age, 52 \u00b1 14.6 y; 55% male; and 87.6% white). The most common physician-identified etiologies were alcohol (45.8%) and idiopathic (24.3%); 15.6% of patients reported no abdominal pain in the year before enrollment. The most common individual pain pattern was described as constant mild pain with episodes of severe pain and was reported in 45% of patients. The most common imaging findings included pancreatic ductal dilatation (68%), atrophy (57%), and calcifications (55%). Imaging findings were categorized as obstructive for 20% and as inflammatory for 25% of cases. The distribution of individual imaging findings was similar among patients with different patterns of pain. The distribution of pain patterns did not differ among clinically relevant groups of imaging findings. CONCLUSIONS Mechanisms that determine patterns and severity of pain in patients with chronic pancreatitis are largely independent of structural variants observed by abdominal imaging techniques. Pancreas-relevant quantitative and qualitative pain measures should be included in the evaluation of patients with chronic pancreatitis to assess pain severity independently of imaging findings.", "author" : [ { "dropping-particle" : "", "family" : "Wilcox", "given" : "C Mel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yadav", "given" : "Dhiraj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ye", "given" : "Tian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gardner", "given" : "Timothy B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gelrud", "given" : "Andres", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandhu", "given" : "Bimaljit S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lewis", "given" : "Michele D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Al-Kaade", "given" : "Samer", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cote", "given" : "Gregory A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forsmark", "given" : "Christopher E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guda", "given" : "Nalini M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Conwell", "given" : "Darwin L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banks", "given" : "Peter A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muniraj", "given" : "Thiruvengadam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Romagnuolo", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brand", "given" : "Randall E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slivka", "given" : "Adam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sherman", "given" : "Stuart", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wisniewski", "given" : "Stephen R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Whitcomb", "given" : "David C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anderson", "given" : "Michelle A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2015", "3" ] ] }, "note" : "NULL", "page" : "552-60; quiz e28-9", "title" : "Chronic pancreatitis pain pattern and severity are independent of abdominal imaging findings.", "type" : "article-journal", "volume" : "13" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(6)", "plainTextFormattedCitation" : "(6)", "previouslyFormattedCitation" : "(6)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(6). Other smaller studies also provide support for the contention that morphological changes do not correlate with painADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0036-5521", "PMID" : "6740208", "abstract" : "In 101 patients with suspected or definite chronic pancreatitis a pancreatic function test, endoscopic retrograde pancreatography, and an interview with special regard to pain were performed. Decrease in pancreatic function was correlated to dilatation of the pancreatic duct system. However, no correlation between the duct morphology and the severity of pain was found. Patients with pancreatic pseudocysts were evenly distributed among the groups in accordance with pancreatic function, but they seemed to be concentrated in the groups with severe pain.", "author" : [ { "dropping-particle" : "", "family" : "Jensen", "given" : "A R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matzen", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Malchow-M\u00f8ller", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Christoffersen", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of gastroenterology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "1984", "5" ] ] }, "note" : "NULL", "page" : "334-8", "title" : "Pattern of pain, duct morphology, and pancreatic function in chronic pancreatitis. A comparative study.", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(29)", "plainTextFormattedCitation" : "(29)", "previouslyFormattedCitation" : "(29)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(29). Attenuation of pain with lessening of inflammation by natural history, medical or surgical intervention. A recurring controversy in the field has been whether pain in CP recedes. In the study by Amman et al, pain patterns were more evident early in the course of the disease and with time both apparently gradually dissipated. Hence, more than 80% of patients with alcoholic pancreatitis were pain-free 10 years after the onset with the same proportion of patients also exhibiting severe pancreatic insufficiency; at this stage about 50% were diabetic, presumably reflecting endocrine failureADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0016-5085", "PMID" : "10220505", "abstract" : "BACKGROUND & AIMS The pain pattern of chronic pancreatitis (CP) and its surgical implications are discussed. The aim of this study was to (1) define typical pain patterns, (2) correlate pain patterns with the presumptive causes of the pain, and (3) compare the natural history of patients treated conservatively or surgically with respect to pain relief, pancreatic dysfunction, and clinical outcome. METHODS A cohort in this prospective long-term study included 207 patients with alcoholic CP (91 without and 116 with surgery for pain relief). A clinically based staging system was applied to characterize pain in the evolution from onset to end-stage CP. RESULTS Average duration of CP was 17 years. In early-stage CP, episodes of recurrent (acute) pancreatitis predominated. Chronic pain was typically associated with local complications (mainly pseudocysts, 84 of 155; 54%), relieved definitely by a single (drainage) procedure in approximately two thirds of patients. Additional surgery was required for late pain recurrence in 39 patients (34%), primarily symptomatic cholestasis (18 of 39; 46%). All patients achieved complete pain relief in advanced CP. CONCLUSIONS In our experience, relief of chronic pain regularly follows selective surgery tailored to the presumptive pain cause or occurs spontaneously in uncomplicated advanced CP.", "author" : [ { "dropping-particle" : "", "family" : "Ammann", "given" : "R W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muellhaupt", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "1999", "5" ] ] }, "note" : "NULL", "page" : "1132-40", "title" : "The natural history of pain in alcoholic chronic pancreatitis.", "type" : "article-journal", "volume" : "116" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(8)", "plainTextFormattedCitation" : "(8)", "previouslyFormattedCitation" : "(8)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(8). This has led this group to champion the so-called “burn-out” theory for pain in CP; however no evidence exists that it is actually the inflammation that is burnt out instead of just functional pancreatic parenchyma. Further, others have refuted this, most convincingly by the NAPS2 study, which showed that neither pain pattern nor severity changed with the duration of the disease, albeit based on patient recall dataADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/gut.2010.213835", "ISSN" : "1468-3288", "PMID" : "21148579", "abstract" : "OBJECTIVE To compare patients with chronic pancreatitis (CP) with constant pain patterns to patients with CP with intermittent pain patterns. METHODS This was a prospective cohort study conducted at 20 tertiary medical centers in the USA comprising 540 subjects with CP. Patients with CP were asked to identify their pain from five pain patterns (A-E) defined by the temporal nature (intermittent or constant) and the severity of the pain (mild, moderate or severe). Pain pattern types were compared with respect to a variety of demographic, quality of life (QOL) and clinical parameters. Rates of disability were the primary outcome. Secondary outcomes included: use of pain medications, days lost from school or work, hospitalisations (preceding year and lifetime) and QOL as measured using the Short Form-12 (SF-12) questionnaire. RESULTS Of the 540 CP patients, 414 patients (77%) self-identified with a particular pain pattern and were analysed. Patients with constant pain, regardless of severity, had higher rates of disability, hospitalisation and pain medication use than patients with intermittent pain. Patients with constant pain had lower QOL (by SF-12) compared with patients who had intermittent pain. Additionally, patients with constant pain were more likely to have alcohol as the aetiology for their pancreatitis. There was no association between the duration of the disease and the quality or severity of the pain. CONCLUSIONS This is the largest study ever conducted of pain in CP. These findings suggest that the temporal nature of pain is a more important determinant of health-related QOL and healthcare utilisation than pain severity. In contrast to previous studies, the pain associated with CP was not found to change in quality over time. These results have important implications for improving our understanding of the mechanisms underlying pain in CP and for the goals of future treatments and interventions.", "author" : [ { "dropping-particle" : "", "family" : "Mullady", "given" : "Daniel K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yadav", "given" : "Dhiraj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Amann", "given" : "Stephen T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Connell", "given" : "Michael R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barmada", "given" : "Michael M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elta", "given" : "Grace H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scheiman", "given" : "James M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wamsteker", "given" : "Erik-Jan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chey", "given" : "William D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Korneffel", "given" : "Meredith L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weinman", "given" : "Beth M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slivka", "given" : "Adam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sherman", "given" : "Stuart", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hawes", "given" : "Robert H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brand", "given" : "Randall E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burton", "given" : "Frank R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lewis", "given" : "Michele D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gardner", "given" : "Timothy B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gelrud", "given" : "Andres", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "DiSario", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baillie", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banks", "given" : "Peter A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Whitcomb", "given" : "David C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anderson", "given" : "Michelle A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "NAPS2 Consortium", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gut", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2011", "1", "1" ] ] }, "page" : "77-84", "title" : "Type of pain, pain-associated complications, quality of life, disability and resource utilisation in chronic pancreatitis: a prospective cohort study.", "type" : "article-journal", "volume" : "60" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(7)", "plainTextFormattedCitation" : "(7)", "previouslyFormattedCitation" : "(7)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(7). Another way to approach this relationship is to examine “therapeutic trials” with interventions directed primarily at inflammation. Unfortunately, there is a paucity of such interventions with anti-oxidants being the most studied class of agents, under the reasonable assumption that this will be associated with a reduction in inflammation. A Cochrane review of 12 such studies concluded that there was a slight reduction in the intensity of pain but no change in the proportion of patients that were pain free, thus making it difficult to draw a firm conclusionADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/14651858.CD008945.pub2", "ISSN" : "1469-493X", "PMID" : "25144441", "abstract" : "BACKGROUND Reduced intake and absorption of antioxidants due to pain and malabsorption are probable causes of the lower levels of antioxidants observed in patients with chronic pancreatitis (CP). Improving the status of antioxidants might be effective in slowing the disease process and reducing pain in CP. OBJECTIVES To assess the benefits and harms of antioxidants for the treatment of pain in patients with CP. SEARCH METHODS We searched\u00a0the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Conference Proceedings Citation Index from inception to October 2012. Two review authors performed the selection of trials independently. SELECTION CRITERIA We included all randomised controlled trials (RCTs) evaluating antioxidants for treatment of pain in CP. All trials were included irrespective of blinding, numbers of participants randomly assigned and language of the article. DATA COLLECTION AND ANALYSIS Two review authors extracted data independently. The risk of bias of included trials was assessed. Study authors were asked for additional information in the case of missing data. MAIN RESULTS Twelve RCTs with a total of 585 participants were included. Six trials were double-blinded, placebo-controlled studies, and the other six trials were of less adequate methodology. Most trials were small and had high rates of dropout. Eleven of the 12 included trials described the effects of antioxidants on chronic abdominal pain in chronic pancreatitis. Pain as measured on a visual analogue scale (VAS, scale range 0 to 10) after one to six months was less in the antioxidant group than in the control group (mean difference (MD) -0.33, 95% confidence interval (CI) -0.64 to -0.02, P value 0.04, moderate-quality evidence). The number of pain-free participants was not statistically significantly different (risk ratio (RR) 1.73, 95% CI 0.95 to 3.15, P value 0.07, low-quality evidence). More adverse events were observed in the antioxidant group, both in the parallel trials (RR 4.43, 95% CI 1.60 to 12.29, P value 0.0004, moderate-quality evidence) and in the cross-over trials (RR 5.80, 95% CI 1.56 to 21.53, P value 0.0009, moderate-quality evidence). Adverse events occurred in 16% of participants and were mostly mild (e.g. headache, gastrointestinal complaints), but were sufficient to make participants stop antioxidant use. Other important outcomes such as use of analgesics, exacerbation of pancreatitis and quality of life were rarely reported. One \u2026", "author" : [ { "dropping-particle" : "", "family" : "Ahmed Ali", "given" : "Usama", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jens", "given" : "Sjoerd", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Busch", "given" : "Olivier RC", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keus", "given" : "Frederik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goor", "given" : "Harry", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gooszen", "given" : "Hein G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boermeester", "given" : "Marja A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cochrane Database of Systematic Reviews", "editor" : [ { "dropping-particle" : "", "family" : "Ahmed Ali", "given" : "Usama", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2014", "8", "21" ] ] }, "note" : "NULL", "page" : "CD008945", "publisher" : "John Wiley & Sons, Ltd", "publisher-place" : "Chichester, UK", "title" : "Antioxidants for pain in chronic pancreatitis", "type" : "chapter" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(30)", "plainTextFormattedCitation" : "(30)", "previouslyFormattedCitation" : "(30)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(30). It is much more difficult to use surgical or endoscopic approaches in this way as determining any effect of putative reduction in inflammation from these interventions would be seriously flawed by the presence of multiple and complicated confounding factors. Even so, there have been no studies that directly examine the relationship between the degree of inflammation found at pancreatectomy and subsequent pain relief (although there are several descriptions relating this to pre-surgical pain status, as described above).Neuropathic and Dysfunctional PainEvidence from animal models has provided convincing evidence that CP results in hypersensitivity of pain responses to pancreatic stimulation, associated with impressive sensitization of the primary nociceptive neuron with specific electrophysiological and molecular changes (such as a reduction in the IA current and changes in the expression of TRPV1, neuropeptides and other factors). These appear to be driven by factors in the milieu of CP such as NGF and more recently, TGFADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nrgastro.2011.274", "ISBN" : "1759-5053 (Electronic) 1759-5045 (Linking)", "ISSN" : "1759-5053", "PMID" : "22269952", "abstract" : "Chronic pancreatitis is typically a painful condition and it can be associated with a severe burden of disease. The pathogenesis of pain in this disorder is poorly understood and its treatment has been largely empirical, often consisting of surgical or other invasive methods, with an outcome that is variable and frequently unsatisfactory. Human and experimental studies have indicated a critical role for neuronal mechanisms that result in peripheral and central sensitization. The pancreatic nociceptor seems to be significantly affected in this condition, with increased excitability associated with downregulation of potassium currents. Some of the specific molecules implicated in this process include the vanilloid receptor, TRPV1, nerve growth factor, the protease activated receptor 2 and a variety of others that are discussed in this Review. Studies have also indicated novel therapeutic targets for this condition.", "author" : [ { "dropping-particle" : "", "family" : "Pasricha", "given" : "Pankaj Jay", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jay", "given" : "Pankaj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature reviews. Gastroenterology & hepatology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2012", "1", "24" ] ] }, "page" : "140-51", "publisher" : "Nature Publishing Group", "title" : "Unraveling the mystery of pain in chronic pancreatitis.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1186/1744-8069-8-65", "ISSN" : "1744-8069", "PMID" : "22963239", "abstract" : "BACKGROUND Transforming growth factor beta (TGF\u03b2) is upregulated in chronic inflammation, where it plays a key role in wound healing and promoting fibrosis. However, little is known about the peripheral effects of TGF\u03b2 on nociception. METHODS We tested the in vitro effects of TGF\u03b21 on the excitability of dorsal root ganglia (DRG) neurons and the function of potassium (K) channels. We also studied the effects of TGF\u03b21 infusion on pain responses to noxious electrical stimulation in healthy rats as well as the effects of neutralization of TGF\u03b21 on evoked pain behaviors in a rat model of chronic pancreatitis. RESULTS Exposure to TGF\u03b21 in vitro increased sensory neuronal excitability, decreased voltage-gated A-type K(+) currents (IA) and downregulated expression of the Kv1.4 (KCNA4) gene. Further TGF\u03b21 infusion into the na\u00efve rat pancreas in vivo induces hyperalgesia and conversely, neutralization of TGF\u03b21 attenuates hyperalgesia only in rats with experimental chronic pancreatitis. Paradoxically, TGF\u03b21 neutralization in na\u00efve rats results in pancreatic hyperalgesia. CONCLUSIONS TGF\u03b21 is an important and complex modulator of sensory neuronal function in chronic inflammation, providing a link between fibrosis and nociception and is a potentially novel target for the treatment of persistent pain associated with chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Zhu", "given" : "Yaohui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Colak", "given" : "Tugba", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shenoy", "given" : "Mohan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Liansheng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mehta", "given" : "Kshama", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pai", "given" : "Reetesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zou", "given" : "Bende", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xie", "given" : "Xinmin Simon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pasricha", "given" : "Pankaj J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Molecular pain", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2012", "9", "11" ] ] }, "note" : "NULL", "page" : "65", "title" : "Transforming growth factor beta induces sensory neuronal hyperexcitability, and contributes to pancreatic pain and hyperalgesia in rats with chronic pancreatitis.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(24,31)", "plainTextFormattedCitation" : "(24,31)", "previouslyFormattedCitation" : "(24,31)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(24,31). Animal models also suggest a component of central sensitization including potential roles for spinal glial activation and descending inhibitory pathways facilitated by the rostral ventromedial medulla (RVM)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.neuroscience.2010.02.005", "ISSN" : "1873-7544", "PMID" : "20149842", "abstract" : "One of the most important symptoms in chronic pancreatitis (CP) is constant and recurrent abdominal pain. However, there is still no ideal explanation and treatment on it. Previous studies indicated that pain in CP shared many characteristics of neuropathic pain. As an important mechanism underlying neuropathic pain, astrocytic activation is probably involved in pain of CP. Based on the trinitrobenzene sulfonic acid (TNBS)-induce rat CP model, we performed pancreatic histology to assess the severity of CP with semiquantitative scores and tested the nociceptive behaviors following induction of CP. Glial fibrillary acidic protein (GFAP) expressions in the thoracic spinal cord were observed by immunohistochemistry and real-time reverse transcription polymerase chain reaction (RT-PCR). Meanwhile, we injected intrathecally astrocytic specific inhibitor l-alpha-aminoadipate (LAA) and observed its effect on nociception induced by CP. Compared to the naive and sham group, TNBS produced long lasting pancreatitis, and persistent mechanical hypersensitivity in the abdomen that was evident 1 week after TNBS infusion and persisted up to 5 weeks. Compared with naive or sham operated rats, GFAP staining was significantly increased 5 weeks after CP induction. Real-time RT-PCR indicated that GFAP expression was significantly increased in TNBS treated rats compared to the sham group. TNBS-induced astrocytic activation was significantly attenuated by LAA, compared with the saline control. Treatment with LAA significantly, even though not completely, attenuated the allodynia. Our results provide for the first time that astrocytes may play a critical role in pain of CP. Some actions could be taken to prevent astrocytic activation to treat pain in CP patients.", "author" : [ { "dropping-particle" : "", "family" : "Feng", "given" : "Q X", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Feng", "given" : "X Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mei", "given" : "X P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhu", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Z C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Y Q", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dou", "given" : "K F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Q C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Neuroscience", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2010", "5", "5" ] ] }, "note" : "NULL", "page" : "501-9", "title" : "Astrocytic activation in thoracic spinal cord contributes to persistent pain in rat model of chronic pancreatitis.", "type" : "article-journal", "volume" : "167" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1053/j.gastro.2011.09.041", "ISSN" : "1528-0012", "PMID" : "21963786", "abstract" : "BACKGROUND & AIMS The chronic, persistent pain associated with chronic pancreatitis (CP) has many characteristics of neuropathic pain, initiated and maintained by the activation of spinal microglia. We investigated whether activated microglia in the thoracic spinal cord contribute to chronic pain in a rat model of CP. METHODS CP was induced in Sprague-Dawley rats by an intraductal injection of 2% trinitrobenzene sulfonic acid. Hyperalgesia was assessed by the measurement of mechanical sensitivity of the abdomen and nocifensive behavior to electrical stimulation of the pancreas. Three weeks after induction of CP, spinal samples were analyzed by immunostaining and immunoblot analyses for levels of CD11 (a marker of microglia, determined with the antibody OX42) and phosphorylated p38 (P-p38, a marker of activation of p38 mitogen-activated protein kinase signaling). We examined the effects of minocycline (inhibitor of microglia) and fractalkine (microglia-activating factor) on visceral hyperalgesia in rats with CP. RESULTS Rats with CP had increased sensitivity and nociceptive behaviors to mechanical probing of the abdomen and electrical stimulation of the pancreas. The dorsal horn of the thoracic spinal cords of rats with CP contained activated microglia (based on increased staining with OX42), with an ameboid appearance. Levels of P-p38 increased in rats with CP and colocalized with OX42-positive cells. Intrathecal injection of minocycline reversed and prevented the increase of nocifensive behaviors and levels of P-p38 in rats with CP. Fractalkine induced hyperalgesia in rats without CP, which was blocked by minocycline. CONCLUSIONS Activated spinal microglia have important roles in maintaining and initiating chronic pain in a rat model of CP. Microglia might be a target for treatment of hyperalgesia caused by pancreatic inflammation.", "author" : [ { "dropping-particle" : "", "family" : "Liu", "given" : "Pei-Yi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lu", "given" : "Ching-Liang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Chia-Chuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "I-Hui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hsieh", "given" : "Jen-Chuen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Chun-Chia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Hsing-Feng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lin", "given" : "Han-Chieh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chang", "given" : "Full-Young", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Shou-Dong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2012", "1" ] ] }, "note" : "NULL", "page" : "165-173.e2", "title" : "Spinal microglia initiate and maintain hyperalgesia in a rat model of chronic pancreatitis.", "type" : "article-journal", "volume" : "142" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1053/j.gastro.2006.03.025", "ISSN" : "0016-5085", "PMID" : "16762636", "abstract" : "BACKGROUND & AIMS Pain is a main complaint of patients with pancreatitis. We hypothesized that such pain is mediated through ascending pathways via the nucleus gracilis (NG) and is dependent on descending facilitatory influences from the rostral ventromedial medulla (RVM). METHODS A rat model of persistent experimental pancreatitis was used. After establishment of pancreatitis, rats received microinjection of lidocaine in the NG or in the RVM to determine the importance of neural activity at these supraspinal sites in the expression of abdominal hypersensitivity evoked by von Frey filaments (ie, pancreatic pain). Rats also were pretreated for 28 days before induction of pancreatitis with a single RVM microinjection of dermorphin-saporin to eliminate cells that drive descending facilitation. Dynorphin content was measured in the spinal cord of pancreatitic rats and the effects of spinal antidynorphin antiserum in pancreatic pain were assessed. RESULTS Microinjection of lidocaine into either the NG or the RVM produced a time-related reversal of pancreatitis-induced pain. Pancreatitis significantly increased thoracic spinal dynorphin content and spinal antidynorphin antiserum elicited a time-related reversal of abdominal hypersensitivity. RVM dermorphin-saporin injection prevented the maintenance, but not the expression, of pancreatitis abdominal hypersensitivity and also prevented the increase of spinal dynorphin content in animals with pancreatitis. CONCLUSIONS Our findings suggest that descending facilitation from the RVM plays a critical role in the maintenance, but not the expression, of pancreatic pain. These results provide a novel insight into the role of descending pathways and spinal plasticity in the maintenance of visceral pain from pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Vera-Portocarrero", "given" : "Louis P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xie", "given" : "Jennifer Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yie", "given" : "Jennifer X", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kowal", "given" : "Justin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ossipov", "given" : "Michael H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "King", "given" : "Tamara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Porreca", "given" : "Frank", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-3", "issue" : "7", "issued" : { "date-parts" : [ [ "2006", "6" ] ] }, "note" : "NULL", "page" : "2155-64", "title" : "Descending facilitation from the rostral ventromedial medulla maintains visceral pain in rats with experimental pancreatitis.", "type" : "article-journal", "volume" : "130" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(32\u201334)", "plainTextFormattedCitation" : "(32\u201334)", "previouslyFormattedCitation" : "(32\u201334)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(32–34). Corresponding evidence for humans with CP is also beginning to emerge. Patients with severe CP have lower pain and expanded pain referral areas thresholds than patients with moderate CP or healthy volunteers, as measured by pressure and electric stimuli in selected dermatomes, reflecting somatic hyperalgesia and allodynia, which is a reflection of spinal sensitizationADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0055460", "ISSN" : "1932-6203", "PMID" : "23405154", "abstract" : "BACKGROUND The most dominant feature in chronic pancreatitis is intense abdominal pain. Changes in spinal and/or supraspinal central nervous system pain processing due to visceral nociceptive input play an important role in this pain. How altered pain processing is related to disease stage still needs study. METHODOLOGY/PRINCIPAL FINDINGS Sixty chronic pancreatitis patients were compared to 15 healthy controls. Two subgroups of pancreatitis patients were defined based on the M-ANNHEIM severity index of chronic pancreatitis; i.e. moderate and severe. Pain detection and tolerance thresholds for pressure and electric stimuli were measured in six selected dermatomes (C5, T4, T10, L1, L4 and T10BACK). In addition, the conditioned pain modulation response to cold pressor task was determined. These measures were compared between the healthy controls and chronic pancreatitis patients. Severe pancreatitis patients showed lower pain thresholds than moderate pancreatitis patients or healthy volunteers. Healthy controls showed a significantly larger conditioned pain modulation response compared to all chronic pancreatitis patients taken together. CONCLUSIONS/SIGNIFICANCE The present study confirms that chronic pancreatitis patients show signs of altered central processing of nociception compared to healthy controls. The study further suggests that these changes, i.e. central sensitization, may be influenced by disease stage. These findings underline the need to take altered central pain processing into account when managing the pain of chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Bouwense", "given" : "Stefan A W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olesen", "given" : "S\u00f8ren S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fr\u00f8kj\u00e6r", "given" : "Jens B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goor", "given" : "Harry", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "Oliver H G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "editor" : [ { "dropping-particle" : "", "family" : "Milanese", "given" : "Steve", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2013", "2", "6" ] ] }, "note" : "NULL", "page" : "e55460", "title" : "Is altered central pain processing related to disease stage in chronic pancreatitis patients with pain? An exploratory study.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1053/j.gastro.2007.01.037", "ISSN" : "00165085", "PMID" : "17408654", "abstract" : "BACKGROUND & AIMS In various chronic pain conditions cortical reorganization seems to play a role in the manifestations. The aim of this study was to investigate cortical reorganization in patients with pain caused by chronic pancreatitis. METHODS Twelve healthy subjects and 10 patients with chronic pancreatitis were included. The esophagus, stomach, and duodenum were stimulated electrically at the pain threshold using a nasal endoscope. The electroencephalogram was recorded from 64 surface electrodes and event-related brain potentials (EPs) were obtained. RESULTS As compared with healthy subjects, the patient group showed decreased latencies of the early EP components (N1, P < .001; P1, P = .02), which is thought to reflect the exogenous brain pain processing specifically. Source analysis showed that the dipolar activities corresponding to the early EPs were located consistently in the bilateral insula, in the anterior cingulate gyrus, and in the bilateral secondary somatosensory area. The bilateral insular dipoles were localized more medial in the patient group than in the healthy subjects after stimulation of all 3 gut segments (P < .01). There also were changes in the cingulate cortex where the neuronal source was more posterior in patients than in controls to stimulation of the esophagus (P < .05). CONCLUSIONS The findings indicate that pain in chronic pancreatitis leads to changes in cortical projections of the nociceptive system. Such findings also have been described in somatic pain disorders, among them neuropathic pain. Taken together with the clinical data this suggests a neuropathic component in pancreatic pain, which may influence the approach to treatment.", "author" : [ { "dropping-particle" : "", "family" : "Dimcevski", "given" : "Georg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sami", "given" : "Saber A.K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Funch\u2013Jensen", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pera", "given" : "Domenica", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valeriani", "given" : "Massimiliano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arendt\u2013Nielsen", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2007", "4" ] ] }, "page" : "1546-1556", "title" : "Pain in Chronic Pancreatitis: The Role of Reorganization in the Central Nervous System", "type" : "article-journal", "volume" : "132" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(35,36)", "plainTextFormattedCitation" : "(35,36)", "previouslyFormattedCitation" : "(35,36)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(35,36). Alterations in descending inhibitory influences on spinal nociceptive neurons have been inferred based on changes in sensation at remote sitesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0055460", "ISSN" : "1932-6203", "PMID" : "23405154", "abstract" : "BACKGROUND The most dominant feature in chronic pancreatitis is intense abdominal pain. Changes in spinal and/or supraspinal central nervous system pain processing due to visceral nociceptive input play an important role in this pain. How altered pain processing is related to disease stage still needs study. METHODOLOGY/PRINCIPAL FINDINGS Sixty chronic pancreatitis patients were compared to 15 healthy controls. Two subgroups of pancreatitis patients were defined based on the M-ANNHEIM severity index of chronic pancreatitis; i.e. moderate and severe. Pain detection and tolerance thresholds for pressure and electric stimuli were measured in six selected dermatomes (C5, T4, T10, L1, L4 and T10BACK). In addition, the conditioned pain modulation response to cold pressor task was determined. These measures were compared between the healthy controls and chronic pancreatitis patients. Severe pancreatitis patients showed lower pain thresholds than moderate pancreatitis patients or healthy volunteers. Healthy controls showed a significantly larger conditioned pain modulation response compared to all chronic pancreatitis patients taken together. CONCLUSIONS/SIGNIFICANCE The present study confirms that chronic pancreatitis patients show signs of altered central processing of nociception compared to healthy controls. The study further suggests that these changes, i.e. central sensitization, may be influenced by disease stage. These findings underline the need to take altered central pain processing into account when managing the pain of chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Bouwense", "given" : "Stefan A W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olesen", "given" : "S\u00f8ren S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fr\u00f8kj\u00e6r", "given" : "Jens B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goor", "given" : "Harry", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "Oliver H G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "editor" : [ { "dropping-particle" : "", "family" : "Milanese", "given" : "Steve", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2013", "2", "6" ] ] }, "note" : "NULL", "page" : "e55460", "title" : "Is altered central pain processing related to disease stage in chronic pancreatitis patients with pain? An exploratory study.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1053/j.gastro.2007.01.037", "ISSN" : "00165085", "PMID" : "17408654", "abstract" : "BACKGROUND & AIMS In various chronic pain conditions cortical reorganization seems to play a role in the manifestations. The aim of this study was to investigate cortical reorganization in patients with pain caused by chronic pancreatitis. METHODS Twelve healthy subjects and 10 patients with chronic pancreatitis were included. The esophagus, stomach, and duodenum were stimulated electrically at the pain threshold using a nasal endoscope. The electroencephalogram was recorded from 64 surface electrodes and event-related brain potentials (EPs) were obtained. RESULTS As compared with healthy subjects, the patient group showed decreased latencies of the early EP components (N1, P < .001; P1, P = .02), which is thought to reflect the exogenous brain pain processing specifically. Source analysis showed that the dipolar activities corresponding to the early EPs were located consistently in the bilateral insula, in the anterior cingulate gyrus, and in the bilateral secondary somatosensory area. The bilateral insular dipoles were localized more medial in the patient group than in the healthy subjects after stimulation of all 3 gut segments (P < .01). There also were changes in the cingulate cortex where the neuronal source was more posterior in patients than in controls to stimulation of the esophagus (P < .05). CONCLUSIONS The findings indicate that pain in chronic pancreatitis leads to changes in cortical projections of the nociceptive system. Such findings also have been described in somatic pain disorders, among them neuropathic pain. Taken together with the clinical data this suggests a neuropathic component in pancreatic pain, which may influence the approach to treatment.", "author" : [ { "dropping-particle" : "", "family" : "Dimcevski", "given" : "Georg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sami", "given" : "Saber A.K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Funch\u2013Jensen", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pera", "given" : "Domenica", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valeriani", "given" : "Massimiliano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arendt\u2013Nielsen", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2007", "4" ] ] }, "page" : "1546-1556", "title" : "Pain in Chronic Pancreatitis: The Role of Reorganization in the Central Nervous System", "type" : "article-journal", "volume" : "132" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.ejpain.2005.06.006", "ISSN" : "1090-3801", "PMID" : "16087373", "abstract" : "BACKGROUND The pain of chronic pancreatitis remains challenging to manage, with treatment all too often being unsuccessful. A main reason for this is lacking understanding of underlying mechanisms of chronic pain in these patients. AIM To document, using somatic quantitative sensory testing, changes in central nervous system processing (neuroplasticity) associated with chronic pancreatitis pain and thus gain insight into underlying pain mechanisms. PATIENTS AND METHODS We studied 10 chronic pancreatitis patients on stable opioid analgesic medication. Ten matched surgical patients without pain served as controls. Pain verbal numeric rating scores (NRS) and thresholds to electric skin stimulation and pressure pain were measured in dermatomes T10 (pancreatic area), C5, T4, L1 and L4. RESULTS The pancreatitis patients had a median NRS pain score of 5 (range 3-8). Electric sensation and pain thresholds were significantly increased in the pancreatic region, tending to be more so in female pancreatitis patients. Pressure pain thresholds were significantly lower in pancreatitis patients than in controls, with men tending towards greater generalised relative hyperalgesia than women. CONCLUSIONS Chronic pancreatitis patients show pronounced generalised deep hyperalgesia that is present despite opioid therapy. These signs, consistent with central sensitisation, appear relatively more prominent in men than women. There is also evidence suggesting that women may have a better segmental inhibitory response than men, possibly explaining their relatively less prominent generalised deep tissue hyperalgesia compared to men.", "author" : [ { "dropping-particle" : "", "family" : "Buscher", "given" : "Hessel C J L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "Oliver H G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goor", "given" : "Harry", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "European journal of pain (London, England)", "id" : "ITEM-3", "issue" : "4", "issued" : { "date-parts" : [ [ "2006", "5" ] ] }, "note" : "NULL", "page" : "363-70", "title" : "Chronic pancreatitis patients show hyperalgesia of central origin: a pilot study.", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1016/j.cgh.2010.03.005", "ISSN" : "1542-7714", "PMID" : "20304100", "abstract" : "BACKGROUND & AIMS Pain is a prominent symptom in chronic pancreatitis (CP), but the underlying mechanisms are incompletely understood. We investigated the role of descending pain modulation from supraspinal structures as well as central nervous system sensitization in patients with pain from CP. METHODS Twenty-five patients with CP and 15 healthy volunteers were included. Descending pain modulation was investigated by diffuse noxious inhibitory control (a descending inhibitory response after conditioning stimulation). Central pain processing was investigated as the perceptual responses to multimodal (electrical, thermal, and mechanical) stimulations of the rectosigmoid and evoked brain potentials after electrical stimulation of the rectosigmoid. RESULTS Compared with healthy volunteers, the efficacy of diffuse noxious inhibitory control was reduced in patients with CP (13% +/- 21% vs 39% +/- 22%, respectively; F = 3.8; P = .01); central sensitization was indicated by remote hyperalgesia in the rectosigmoid to electrical stimulation (21 +/- 15 mA vs 27 +/- 15 mA; F = 6.2; P = .02) and heat stimulation (51 degrees C +/- 5 degrees C vs 53 degrees C +/- 4 degrees C; F = 5.9; P = .02). Compared with controls, patients with CP had increased latency of the early P1 peak to rectosigmoid stimulation (85 +/- 21 ms vs 108 +/- 28 ms, respectively; P = .02), possibly reflecting reorganization of central pain pathways. CONCLUSIONS Patients with CP have impairments in inhibitory pain modulation and evidence of central sensitization. Treatment of their pain therefore should focus not only on the pancreas, but also on descending pain modulation from supraspinal structures and central nervous system sensitization.", "author" : [ { "dropping-particle" : "", "family" : "Olesen", "given" : "S\u00f8ren Schou", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brock", "given" : "Christina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Krarup", "given" : "Anne Lund", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Funch-Jensen", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arendt-Nielsen", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "Oliver H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn Mohr", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association", "id" : "ITEM-4", "issue" : "8", "issued" : { "date-parts" : [ [ "2010", "8" ] ] }, "note" : "NULL", "page" : "724-30", "title" : "Descending inhibitory pain modulation is impaired in patients with chronic pancreatitis.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(35\u201338)", "plainTextFormattedCitation" : "(35\u201338)", "previouslyFormattedCitation" : "(35\u201338)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(35–38). (Electroencephalograpy (EEG) in patients with CP show functional changes suggesting a maladaptive pain responseADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1053/j.gastro.2007.01.037", "ISSN" : "00165085", "PMID" : "17408654", "abstract" : "BACKGROUND & AIMS In various chronic pain conditions cortical reorganization seems to play a role in the manifestations. The aim of this study was to investigate cortical reorganization in patients with pain caused by chronic pancreatitis. METHODS Twelve healthy subjects and 10 patients with chronic pancreatitis were included. The esophagus, stomach, and duodenum were stimulated electrically at the pain threshold using a nasal endoscope. The electroencephalogram was recorded from 64 surface electrodes and event-related brain potentials (EPs) were obtained. RESULTS As compared with healthy subjects, the patient group showed decreased latencies of the early EP components (N1, P < .001; P1, P = .02), which is thought to reflect the exogenous brain pain processing specifically. Source analysis showed that the dipolar activities corresponding to the early EPs were located consistently in the bilateral insula, in the anterior cingulate gyrus, and in the bilateral secondary somatosensory area. The bilateral insular dipoles were localized more medial in the patient group than in the healthy subjects after stimulation of all 3 gut segments (P < .01). There also were changes in the cingulate cortex where the neuronal source was more posterior in patients than in controls to stimulation of the esophagus (P < .05). CONCLUSIONS The findings indicate that pain in chronic pancreatitis leads to changes in cortical projections of the nociceptive system. Such findings also have been described in somatic pain disorders, among them neuropathic pain. Taken together with the clinical data this suggests a neuropathic component in pancreatic pain, which may influence the approach to treatment.", "author" : [ { "dropping-particle" : "", "family" : "Dimcevski", "given" : "Georg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sami", "given" : "Saber A.K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Funch\u2013Jensen", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pera", "given" : "Domenica", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valeriani", "given" : "Massimiliano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arendt\u2013Nielsen", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2007", "4" ] ] }, "page" : "1546-1556", "title" : "Pain in Chronic Pancreatitis: The Role of Reorganization in the Central Nervous System", "type" : "article-journal", "volume" : "132" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1159/000321644", "ISSN" : "1424-3911", "PMID" : "21273802", "abstract" : "BACKGROUND/AIMS In various chronic pain conditions cortical reorganisation seems to play a role in the symptomatology. The aims of this study were to investigate cortical reorganisation in patients with pain caused by chronic pancreatitis (CP) and to correlate putative cortical reorganisation to clinical pain scores. METHODS 24 patients suffering from CP and 14 healthy volunteers were included. Patients' daily experience of pain was recorded in a pain diary. The sigmoid was stimulated electrically with simultaneous recording of evoked brain potentials (EPs). The brain source localisations reflecting direct neuronal activity were fitted by a five-dipole model projected to magnetic resonance imaging of the individual brains. RESULTS Patients showed prolonged latencies of the EPs confined to the frontal region of the brain (p < 0.01). The corresponding brain sources were located in the bilateral insula, cingulate gyrus and bilateral secondary somatosensory area. The insular dipoles were localised more posterior in the patients than in healthy subjects (p < 0.01). The shift in insular dipole localisation was negatively correlated with the patients' clinical pain scores (p < 0.05). CONCLUSIONS The findings indicate that sustained pain in CP leads to functional reorganisation of the insular cortex. We suggest its physiological correlate to be an adaptive response to chronic pain. and IAP.", "author" : [ { "dropping-particle" : "", "family" : "Olesen", "given" : "S\u00f8ren Schou", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fr\u00f8kj\u00e6r", "given" : "Jens Br\u00f8ndum", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lelic", "given" : "Dina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valeriani", "given" : "Massimiliano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn Mohr", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2010", "3" ] ] }, "note" : "NULL", "page" : "742-51", "title" : "Pain-associated adaptive cortical reorganisation in chronic pancreatitis.", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1097/MEG.0b013e3283457b09", "ISSN" : "1473-5687", "PMID" : "21399506", "abstract" : "BACKGROUND AND AIM Intractable pain usually dominates the clinical presentation of chronic pancreatitis (CP). Slowing of electroencephalogram (EEG) rhythmicity has been associated with abnormal cortical pain processing in other chronic pain disorders. The aim of this study was to investigate the spectral distribution of EEG rhythmicity in patients with CP. PATIENTS AND METHODS Thirty-one patients with painful CP (mean age 52 years, 19 male) and 15 healthy volunteers (mean age 49, nine male) were included. A multichannel EEG was recorded from 62 surface electrodes. Amplitude strengths of the resting EEG were retrieved based on wavelet frequency analysis and summarized in frequency bands with corresponding topographic mapping. RESULTS Patients with CP had slowed EEG rhythmicity compared with healthy volunteers. This was evident as increased activity in the lower frequency bands \u03b4 (1-3.5 Hz) (P=0.05), \u03b8 (3.5-7.5 Hz) (P<0.001) and \u03b1 (7.5-13.5 Hz) (P<0.001). Due to normalization a reciprocal relationship was observed for the high frequency band \u03b2 (13.5-32 Hz). In a sub-analysis, \u03b4 band activity was modified by diabetes, opioid treatment and alcohol aetiology of CP. However, no effect modification was seen for the \u03b8 or \u03b1 bands. Differences in \u03b8 activity were located over centro-frontal brain regions, whereas differences in \u03b4, \u03b1 and \u03b2 band activity were located in frontal regions. CONCLUSION Slowed EEG rhythmicity was evident in patients with CP. This possibly mirrors abnormal central pain processing and may serve as a clinically useful biomarker of abnormal central pain processing.", "author" : [ { "dropping-particle" : "", "family" : "Olesen", "given" : "S\u00f8ren S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hansen", "given" : "Tine M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graversen", "given" : "Carina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steimle", "given" : "Kristoffer", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "Oliver H G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn Mohr", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European journal of gastroenterology & hepatology", "id" : "ITEM-3", "issue" : "5", "issued" : { "date-parts" : [ [ "2011", "5" ] ] }, "note" : "NULL", "page" : "418-24", "title" : "Slowed EEG rhythmicity in patients with chronic pancreatitis: evidence of abnormal cerebral pain processing?", "type" : "article-journal", "volume" : "23" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.2147/JPR.S50919", "ISSN" : "1178-7090", "PMID" : "24379694", "abstract" : "OBJECTIVES Electroencephalography (EEG) may be a promising source of physiological biomarkers accompanying chronic pain. Several studies in patients with chronic neuropathic pain have reported alterations in central pain processing, manifested as slowed EEG rhythmicity and increased EEG power in the brain's resting state. We aimed to investigate novel potential markers of chronic pain in the resting state EEG of patients with chronic pancreatitis. PARTICIPANTS Resting state EEG data from 16 patients with persistent abdominal pain due to chronic pancreatitis (CP) were compared to data from healthy controls matched for age, sex and education. METHODS The peak alpha frequency (PAF) and power amplitude in the alpha band (7.5-13 Hz) were compared between groups in four regions of interest (frontal, central, parietal, and occipital) and were correlated with pain duration. RESULTS The average PAF was lowered in CP patients compared with that in healthy controls, observed as a statistically significant between-group effect (mean 9.9 versus 9.5 Hz; P=0.049). Exploratory post hoc analysis of average PAF per region of interest revealed a significant difference, particularly in the parietal and occipital regions. In addition, we observed a significant correlation between pain duration and PAF and showed increased shifts in PAF with longer pain durations. No significant group differences were found in peak power amplitudes. CONCLUSION CP pain is associated with alterations in spontaneous brain activity, observed as a shift toward lower PAF. This shift correlates with the duration of pain, which demonstrates that PAF has the potential to be a clinically feasible biomarker for chronic pain. These findings could be helpful for assisting diagnosis, establishing optimal treatment, and studying efficacy of new therapeutic agents in chronic pain patients.", "author" : [ { "dropping-particle" : "", "family" : "Vries", "given" : "Marjan", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "Oliver Hg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "LA", "family" : "Jongsma", "given" : "Marijtje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Broeke", "given" : "Emanuel N", "non-dropping-particle" : "van den", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arns", "given" : "Martijn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goor", "given" : "Harry", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rijn", "given" : "Clementina M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of pain research", "id" : "ITEM-4", "issued" : { "date-parts" : [ [ "2013", "11", "25" ] ] }, "note" : "NULL", "page" : "815-24", "title" : "Altered resting state EEG in chronic pancreatitis patients: toward a marker for chronic pain.", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(36,39\u201341)", "plainTextFormattedCitation" : "(36,39\u201341)", "previouslyFormattedCitation" : "(36,39\u201341)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(36,39–41). In addition to functional changes, there are also morphological effects of CP on the nervous system. This is best demonstrated by the changes in neural density, hypertrophy and both peri- and endo-neural inflammatory infiltration in resected clinical specimensADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1053/j.gastro.2008.09.029", "ISSN" : "1528-0012", "PMID" : "18992743", "abstract" : "BACKGROUND & AIMS Chronic pancreatitis (CP) and pancreatic adenocarcinoma (PCa) are characterized by intrapancreatic neural alterations and pain. Our aims were to: (a) Investigate whether neuropathic changes like pancreatic neuritis, increased neural density, and hypertrophy are phenomena only in CP or whether they are also evident in other pancreatic disorders as well, (b) study possible variations in neural cancer cell invasion among malignant pancreatic tumors, and (c) explore whether these neuropathic changes contribute to pain sensation. METHODS Neuropathic changes were studied in PCa (n=149), in CP (n=141), in pancreatic tumors (PTm) including serous/mucinous cystadenomas, invasive/noninvasive intraductal papillary mucinous neoplasias, benign/malignant neuroendocrine tumors, ampullary cancers (n=196), and in normal pancreas (n=60). The results were correlated with GAP-43 expression, tissue inflammation, pancreatic neuritis, neural invasion, fibrosis, desmoplasia, pain, and patient survival. RESULTS Increased neural density and hypertrophy were only detected in PCa and CP and were strongly associated with GAP-43 over expression and abdominal pain. The severity of pancreatic neuritis was strongest in PCa and was closely linked to changes in neural density and hypertrophy. The aggressiveness of neural cancer cell invasion was most prominent in PCa and was related to neuropathic changes, desmoplasia, and pain. Severe and enduring pain were strongly associated with poor prognosis in PCa patients. CONCLUSIONS Enhanced neural density and hypertrophy are only typical features of CP and PCa among all investigated pancreatic disorders. Such neuropathic changes, including damage to nerves by inflammatory and/or cancer cells, seem to enhance and generate pancreatic neuropathic pain.", "author" : [ { "dropping-particle" : "", "family" : "Ceyhan", "given" : "G\u00fcralp O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergmann", "given" : "Frank", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kadihasanoglu", "given" : "Mustafa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Altintas", "given" : "Burak", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Demir", "given" : "Ihsan E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hinz", "given" : "Ulf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "M\u00fcller", "given" : "Michael W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giese", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "B\u00fcchler", "given" : "Markus W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giese", "given" : "Nathalia A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Friess", "given" : "Helmut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2009", "1" ] ] }, "note" : "NULL", "page" : "177-186.e1", "title" : "Pancreatic neuropathy and neuropathic pain--a comprehensive pathomorphological study of 546 cases.", "type" : "article-journal", "volume" : "136" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(42)", "plainTextFormattedCitation" : "(42)", "previouslyFormattedCitation" : "(42)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(42). The CNS may also be affected as seen by microstructural changes in cingulate and prefrontal cortices. Remarkably, there were differences in brain imaging between patients with episodic versus continuous pain as well as overall correlations between MRI findings and pain scoresADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/gut.2010.236620", "ISSN" : "0017-5749", "author" : [ { "dropping-particle" : "", "family" : "Frokjaer", "given" : "J. B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olesen", "given" : "S. S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gram", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yavarian", "given" : "Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bouwense", "given" : "S. A. W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "O. H. G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "A. M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gut", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2011", "11", "1" ] ] }, "note" : "NULL", "page" : "1554-1562", "title" : "Altered brain microstructure assessed by diffusion tensor imaging in patients with chronic pancreatitis", "type" : "article-journal", "volume" : "60" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(43)", "plainTextFormattedCitation" : "(43)", "previouslyFormattedCitation" : "(43)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(43). “Mechanical” causes of pain.In some cases of chronic pancreatitis, pain may likely be due to large space occupying lesions such as pseudocysts or cancers, or ductal obstruction from strictures or stones. Presumably this kind of pain results from activation of mechanosenstive nociceptive nerves and may represent another primary mechanism in some instances. More often, however, these lesions trigger or exacerbate pain on a background of a nociceptive system that has been sensitized by inflammatory or neuropathic mechanisms as discussed above.Conclusions, Perspective and Future DirectionsPain in CP remains poorly studied and inadequately correlated with neurobiological mechanisms. By definition CP is characterized by inflammation but unlike other inflammatory disorders, there is a paucity of therapeutic attempts targeting this particular aspect of pathophysiology, rendering it difficult to understand how much it contributes to pain. On the other hand, there are striking changes in structure and function in both the peripheral and central nervous system in this condition, lending plausibility to a maladaptive state that includes both neuropathic and dysfunctional pain. In the absence of effective anti-inflammatory approaches, it is clearly important to focus on the alteration of function that accompanies these changes in the nociceptive system as a potential therapeutic target. Pain is a complex and multifactorial phenomenon that affects every aspect of a patients’ life, including emotional, social and physical functioning, and correlates with quality of life in CPADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.pan.2014.09.009", "ISSN" : "1424-3911", "PMID" : "25455540", "abstract" : "BACKGROUND/OBJECTIVES Chronic pancreatitis (CP) is a disabling disease characterised by abdominal pain, and various pancreatic and extra-pancreatic complications. We investigated the interactions between pain characteristics (i.e. pain severity and its pattern in time), complications, and quality of life (QOL) in patients with CP. METHODS This was a cross-sectional study of 106 patients with CP conducted at two North European tertiary medical centres. Detailed information on clinical patient characteristics was obtained from interviews and through review of the individual patient records. Pain severity scores and pain pattern time profiles were extracted from the modified brief pain inventory short form and correlated to QOL as assessed by the EORTC QLQ-C30 questionnaire. Interactions with exocrine and endocrine pancreatic insufficiency, as well as pancreatic and extra-pancreatic complications were analysed using regression models. RESULTS Pain was the most prominent symptom in our cohort and its severity was significantly correlated with EORTC global health status (r = -0.46; P < 0.001) and most functional and symptom subscales. In contrast the patterns of pain in time were not associated with any of the life quality subscales. When controlling for interactions from exocrine and endocrine pancreatic insufficiency no effect modifications were evident (P = 0.72 and P = 0.85 respectively), while the presence of pancreatic and extra-pancreatic complications was associated with an almost 15% decrease in life quality (P = 0.004). CONCLUSIONS Pain severity and disease related complications significantly reduce life quality in patients with CP. This information is important in order to design more accurate and clinical meaningful endpoints in future outcome trials.", "author" : [ { "dropping-particle" : "", "family" : "Olesen", "given" : "S\u00f8ren Schou", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Juel", "given" : "Jacob", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nielsen", "given" : "Anders Klitgaard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fr\u00f8kj\u00e6r", "given" : "Jens Br\u00f8ndum", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "Oliver H G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn Mohr", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2014", "11" ] ] }, "note" : "NULL", "page" : "497-502", "title" : "Pain severity reduces life quality in chronic pancreatitis: Implications for design of future outcome trials.", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(13)", "plainTextFormattedCitation" : "(13)", "previouslyFormattedCitation" : "(13)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(13). Because patients with CP have not been systematically followed using a comprehensive and multidisciplinary approach, it is important to gain an understanding of each of these components, particularly as each has been shown to have relevance in other chronically painful conditions. This is best accomplished by a longitudinal multi-center registry that prospectively studies the outcomes of medical and surgical care of patients with CP, identifies biomarkers for inflammation and provides correlation with histological and molecular changes in pancreatic tissue. Of particular interest are questions that emphasize persistent pain, flare-ups and disability. Such an approach will increase our understanding of the etiology of pain in CP, allow the identification of “high-risk” subgroups for testing medical, surgical, and possibly psychosocial treatment in future clinical trials, and ultimately increase our ability to personalize treatment to the individual’s risk and clinical profile. Claudia M Campbell and Pankaj Jay Pasricha Q3. Which methods are available to assess pancreatic pain and its response to treatment? Assessment of pain in CP follows the guidelines for other types of chronic pain, where the multidimensional nature of symptom presentation is taken into consideration. Only a few instruments have been validated for subjective pain assessment in CP; however, several appropriate measures exist despite not being rigorously validated in this population. (Quality assessment: moderate; Recommendation: strong; Agreement: strong) Pain is complex in nature and interacts with multiple systems, thus systematic, frequent multidimensional pain assessment is required to determine the most efficacious treatment plan, and evaluate effects for patients presenting with painADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Turk DC", "given" : "Melzack R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "edition" : "2nd", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2001" ] ] }, "publisher" : "Guilford Press", "publisher-place" : "New York", "title" : "Handbook of pain assessment", "type" : "book" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Turk DC", "given" : "Melzack R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Handbook of Pain Assessment", "edition" : "2nd", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2201" ] ] }, "page" : "3-11", "publisher" : "Guilford Press", "publisher-place" : "New York", "title" : "The measurement of pain and the assessment of people experiencing pain", "type" : "chapter" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(44,45)", "plainTextFormattedCitation" : "(44,45)", "previouslyFormattedCitation" : "(44,45)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(44,45). As in many idiopathic pain conditions, CP pain is challenging to assess and treat in, for example perceived pain severity may be completely unrelated to observed physical manifestations or symptoms. Given that individual differences in the development, course, and sequelae of a given pain condition are broad, and that observable physical pathology (e.g., duct dilation, atrophy, calcifications) correlates minimally with pain-related symptomatologyADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.cgh.2014.10.015", "ISSN" : "1542-7714", "PMID" : "25424572", "abstract" : "BACKGROUND & AIMS Chronic pancreatitis is characterized by inflammation, atrophy, fibrosis with progressive ductal changes, and functional changes that include variable exocrine and endocrine insufficiency and multiple patterns of pain. We investigated whether abdominal imaging features accurately predict patterns of pain. METHODS We collected data from participants in the North American Pancreatitis Study 2 Continuation and Validation, a prospective multicenter study of patients with chronic pancreatitis performed at 13 expert centers in the United States from July 2008 through March 2012. Chronic pancreatitis was defined based on the detection of characteristic changes by cross-sectional abdominal imaging, endoscopic retrograde cholangiopancreatography, endoscopic ultrasonography, or histology analyses. Patients were asked by a physician or trained clinical research coordinator if they had any abdominal pain during the year before enrollment, those who responded \"yes\" were asked to select from a list of 5 pain patterns. By using these patterns, we\u00a0classified patients' pain based on timing and severity. Abnormal pancreatitis-associated features on abdominal imaging were recorded using standardized case report forms. RESULTS Data were collected from 518 patients (mean age, 52 \u00b1 14.6 y; 55% male; and 87.6% white). The most common physician-identified etiologies were alcohol (45.8%) and idiopathic (24.3%); 15.6% of patients reported no abdominal pain in the year before enrollment. The most common individual pain pattern was described as constant mild pain with episodes of severe pain and was reported in 45% of patients. The most common imaging findings included pancreatic ductal dilatation (68%), atrophy (57%), and calcifications (55%). Imaging findings were categorized as obstructive for 20% and as inflammatory for 25% of cases. The distribution of individual imaging findings was similar among patients with different patterns of pain. The distribution of pain patterns did not differ among clinically relevant groups of imaging findings. CONCLUSIONS Mechanisms that determine patterns and severity of pain in patients with chronic pancreatitis are largely independent of structural variants observed by abdominal imaging techniques. Pancreas-relevant quantitative and qualitative pain measures should be included in the evaluation of patients with chronic pancreatitis to assess pain severity independently of imaging findings.", "author" : [ { "dropping-particle" : "", "family" : "Wilcox", "given" : "C Mel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yadav", "given" : "Dhiraj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ye", "given" : "Tian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gardner", "given" : "Timothy B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gelrud", "given" : "Andres", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandhu", "given" : "Bimaljit S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lewis", "given" : "Michele D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Al-Kaade", "given" : "Samer", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cote", "given" : "Gregory A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forsmark", "given" : "Christopher E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guda", "given" : "Nalini M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Conwell", "given" : "Darwin L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banks", "given" : "Peter A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muniraj", "given" : "Thiruvengadam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Romagnuolo", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brand", "given" : "Randall E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slivka", "given" : "Adam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sherman", "given" : "Stuart", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wisniewski", "given" : "Stephen R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Whitcomb", "given" : "David C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anderson", "given" : "Michelle A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2015", "3" ] ] }, "note" : "NULL", "page" : "552-60; quiz e28-9", "title" : "Chronic pancreatitis pain pattern and severity are independent of abdominal imaging findings.", "type" : "article-journal", "volume" : "13" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(6)", "plainTextFormattedCitation" : "(6)", "previouslyFormattedCitation" : "(6)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(6), other factors must play a role in either facilitating or protecting against the experience of long-term, disabling pain. In addition to pain intensity, which is the only routinely reported outcome in most previous CP studies, assessment of a number of qualities describing the dimensions and characteristics of pain is crucial, including documenting functional impairment and quality of lifeADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.pain.2010.02.018", "ISSN" : "0304-3959", "PMID" : "20207481", "abstract" : "There has been an increase in the number of chronic pain clinical trials in which the treatments being evaluated did not differ significantly from placebo in the primary efficacy analyses despite previous research suggesting that efficacy could be expected. These findings could reflect a true lack of efficacy or methodological and other aspects of these trials that compromise the demonstration of efficacy. There is substantial variability among chronic pain clinical trials with respect to important research design considerations, and identifying and addressing any methodological weaknesses would enhance the likelihood of demonstrating the analgesic effects of new interventions. An IMMPACT consensus meeting was therefore convened to identify the critical research design considerations for confirmatory chronic pain trials and to make recommendations for their conduct. We present recommendations for the major components of confirmatory chronic pain clinical trials, including participant selection, trial phases and duration, treatment groups and dosing regimens, and types of trials. Increased attention to and research on the methodological aspects of confirmatory chronic pain clinical trials has the potential to enhance their assay sensitivity and ultimately provide more meaningful evaluations of treatments for chronic pain.", "author" : [ { "dropping-particle" : "", "family" : "Dworkin", "given" : "Robert H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turk", "given" : "Dennis C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peirce-Sandner", "given" : "Sarah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baron", "given" : "Ralf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bellamy", "given" : "Nicholas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", 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"David M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stauffer", "given" : "Joseph W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stucki", "given" : "Gerold", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tobias", "given" : "Jeffrey", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "White", "given" : "Richard E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Witter", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pain", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2010", "5" ] ] }, "note" : "NULL", "page" : "177-193", "title" : "Research design considerations for confirmatory chronic pain clinical trials: IMMPACT recommendations", "type" : "article-journal", "volume" : "149" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(46)", "plainTextFormattedCitation" : "(46)", "previouslyFormattedCitation" : "(46)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(46). These dimensions are described briefly below along with comments on different scales and frequently used questionnaires that can be used during pain assessment. Additional, somewhat more objective, methods for visualizing or assessing pain are also included along with a discussion of complicating factors and barriers to effective pain management.Pain Dimensions for assessment:CP patients often describe their pain as severe, unremitting, exacerbated by eating and sometimes associated with post-prandial nausea and vomitingADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1177/2049463713479230", "ISSN" : "2049-4637", "PMID" : "26516493", "abstract" : "The pain of chronic pancreatitis represents a major challenge to those working in the field, including pain specialists, gastroenterologists and surgeons. This article describes the different aetiologies of chronic pancreatitis and lists the models for the pathogenesis of pain, including novel ideas such as the role of the immune system in the modulation of pain. The patient profile in chronic pancreatitis is discussed along with the social impact of the disease in relation to alcohol misuse. The range of treatment strategies including medical, endoscopic and surgical approaches are evaluated. Common analgesic regimes and their limitations are reviewed. The pain of chronic pancreatitis remains refractory to effective treatment in many cases and further study and understanding of the underlying pathophysiology are required.", "author" : [ { "dropping-particle" : "", "family" : "Goulden", "given" : "Michael R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "British Journal of Pain", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2013", "2" ] ] }, "note" : "NULL", "page" : "8-22", "title" : "The pain of chronic pancreatitis: a persistent clinical challenge", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(47)", "plainTextFormattedCitation" : "(47)", "previouslyFormattedCitation" : "(47)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(47). Patients also frequently report breakthrough pain or enhanced pain during a “flare-up” which is sudden, unexpected and more intense than their baseline chronic pain level. Both of these distinct pain types should be assessed with regard to the following qualities. Etiology of pain (with respect to onset of symptoms). While diagnoses based on etiology is the current standard in chronic pain, some have suggested that a better approach to assessment, diagnosis, and treatment may be to identify the pathophysiologic mechanisms that “account” for a patient's pain and to then use these mechanisms as the basis for selecting the most appropriate approach to treatmentADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0304-3959", "PMID" : "1701044", "author" : [ { "dropping-particle" : "", "family" : "Max", "given" : "M B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pain", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "1990", "8" ] ] }, "note" : "NULL", "page" : "131-7", "title" : "Towards physiologically based treatment of patients with neuropathic pain.", "type" : "article-journal", "volume" : "42" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0304-3959", "PMID" : "9808347", "author" : [ { "dropping-particle" : "", "family" : "Woolf", "given" : "C J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bennett", "given" : "G J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doherty", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dubner", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kidd", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koltzenburg", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lipton", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loeser", "given" : "J D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Payne", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Torebjork", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pain", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "1998", "9" ] ] }, "note" : "NULL", "page" : "227-9", "title" : "Towards a mechanism-based classification of pain?", "type" : "article-journal", "volume" : "77" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(48,49)", "plainTextFormattedCitation" : "(48,49)", "previouslyFormattedCitation" : "(48,49)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(48,49). While the pathophysiology of CP is unclear, the individual etiology may hint at specific mechanisms and a potential course. Pain duration and chronicity should be evaluated by assessment of the onset and progression of pain over time. It may or may not coincide with the onset of other CP symptoms. Categorizing the pain into intermittent acute, continuous or combined might be appropriate. If the pain has persisted for greater than three months it is considered chronicADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Merskey H", "given" : "Bogduk N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "edition" : "2 ed.", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "1994" ] ] }, "publisher" : "IASP Press", "publisher-place" : "Seattle", "title" : "Classification of chronic pain", "type" : "book" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(50)", "plainTextFormattedCitation" : "(50)", "previouslyFormattedCitation" : "(50)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(50) . As for breakthrough pain, duration may be more limited and time locked to meals, stress, alcohol intake, elimination, etc. A large CP study, conducted approximately five years ago, found that the temporal nature of?pain?was a more influential determinant of healthcare utilization and health-related QOL when compared to?pain?severityADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/gut.2010.213835", "ISSN" : "1468-3288", "PMID" : "21148579", "abstract" : "OBJECTIVE To compare patients with chronic pancreatitis (CP) with constant pain patterns to patients with CP with intermittent pain patterns. METHODS This was a prospective cohort study conducted at 20 tertiary medical centers in the USA comprising 540 subjects with CP. Patients with CP were asked to identify their pain from five pain patterns (A-E) defined by the temporal nature (intermittent or constant) and the severity of the pain (mild, moderate or severe). Pain pattern types were compared with respect to a variety of demographic, quality of life (QOL) and clinical parameters. Rates of disability were the primary outcome. Secondary outcomes included: use of pain medications, days lost from school or work, hospitalisations (preceding year and lifetime) and QOL as measured using the Short Form-12 (SF-12) questionnaire. RESULTS Of the 540 CP patients, 414 patients (77%) self-identified with a particular pain pattern and were analysed. Patients with constant pain, regardless of severity, had higher rates of disability, hospitalisation and pain medication use than patients with intermittent pain. Patients with constant pain had lower QOL (by SF-12) compared with patients who had intermittent pain. Additionally, patients with constant pain were more likely to have alcohol as the aetiology for their pancreatitis. There was no association between the duration of the disease and the quality or severity of the pain. CONCLUSIONS This is the largest study ever conducted of pain in CP. These findings suggest that the temporal nature of pain is a more important determinant of health-related QOL and healthcare utilisation than pain severity. In contrast to previous studies, the pain associated with CP was not found to change in quality over time. These results have important implications for improving our understanding of the mechanisms underlying pain in CP and for the goals of future treatments and interventions.", "author" : [ { "dropping-particle" : "", "family" : "Mullady", "given" : "Daniel K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yadav", "given" : "Dhiraj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Amann", "given" : "Stephen T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Connell", "given" : "Michael R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barmada", "given" : "Michael M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elta", "given" : "Grace H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scheiman", "given" : "James M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wamsteker", "given" : "Erik-Jan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chey", "given" : "William D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Korneffel", "given" : "Meredith L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weinman", "given" : "Beth M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slivka", "given" : "Adam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sherman", "given" : "Stuart", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hawes", "given" : "Robert H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brand", "given" : "Randall E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burton", "given" : "Frank R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lewis", "given" : "Michele D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gardner", "given" : "Timothy B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gelrud", "given" : "Andres", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "DiSario", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baillie", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banks", "given" : "Peter A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Whitcomb", "given" : "David C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anderson", "given" : "Michelle A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "NAPS2 Consortium", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gut", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2011", "1", "1" ] ] }, "page" : "77-84", "title" : "Type of pain, pain-associated complications, quality of life, disability and resource utilisation in chronic pancreatitis: a prospective cohort study.", "type" : "article-journal", "volume" : "60" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(7)", "plainTextFormattedCitation" : "(7)", "previouslyFormattedCitation" : "(7)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(7). Early diagnosis and treatment is important in CP, as repeated episodes of inflammation may produce irreversible damage, and pain relief may be less effective the longer the disorder is left untreated.Pain Intensity is subjective in nature and may vary strongly from person to person as a function of individual differences in pain sensitivity, activity level, diet, substance use, coping strategies, and the severity of the underlying disease, among other factors, many of which are likely yet unknown factors that may vary by the individual. Typically, intensity is queried on a 0-10 numerical pain rating scale where 0 = “no pain” and 10 = “the worst pain you can imagine”ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0162-220X", "PMID" : "9494230", "abstract" : "Pain is difficult to measure, regardless of etiology. Furthermore, the measurement of pain is complicated by variation in the use of visual analogue scales as well as other pain assessment measures. This brief article reviews situations contributing to confusion regarding pain intensity measures and argues for consistency in its measurements with adults not experiencing cognitive disorders in the clinical setting.", "author" : [ { "dropping-particle" : "", "family" : "Dalton", "given" : "J A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McNaull", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cancer nursing", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "1998", "2" ] ] }, "note" : "NULL", "page" : "46-9", "title" : "A call for standardizing the clinical rating of pain intensity using a 0 to 10 rating scale.", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(51)", "plainTextFormattedCitation" : "(51)", "previouslyFormattedCitation" : "(51)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(51). Disease severity, different, but related to pain intensity is most commonly categorized in CP based on the Cambridge Classification system which divides CP into five severity groups based on morphological changes of the main pancreatic duct and its side branches based on ERCP, ultrasound and CTADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0033-8389", "PMID" : "2642274", "abstract" : "This article reviews the use of endoscopic retrograde cholangiopancreatography in chronic pancreatitis and discusses the endoscopic and radiologic techniques necessary for good pancreatography, the indications for its use, and the complications that may arise from it. The Cambridge classification is dealt with in detail together with the abnormalities found in chronic pancreatitis. There is also a short section describing methods of endoscopic therapy in chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Axon", "given" : "A T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Radiologic clinics of North America", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "1989", "1" ] ] }, "note" : "NULL", "page" : "39-50", "title" : "Endoscopic retrograde cholangiopancreatography in chronic pancreatitis. Cambridge classification.", "type" : "article-journal", "volume" : "27" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(52)", "plainTextFormattedCitation" : "(52)", "previouslyFormattedCitation" : "(52)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(52). A more recent classification of CP incorporates risk factors into a categorization schedule, not specifically linked to severity. TIGAR-O evaluates and categorizes CP into toxic-metabolic, idiopathic, genetic, autoimmune, recurrent and severe acute pancreatitis or obstructiveADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.disamonth.2014.11.002", "ISSN" : "1557-8194", "PMID" : "25510320", "author" : [ { "dropping-particle" : "", "family" : "Muniraj", "given" : "Thiruvengadam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aslanian", "given" : "Harry R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Farrell", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jamidar", "given" : "Priya A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Disease-a-month : DM", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2014", "12" ] ] }, "note" : "NULL", "page" : "530-50", "title" : "Chronic pancreatitis, a comprehensive review and update. Part I: epidemiology, etiology, risk factors, genetics, pathophysiology, and clinical features.", "type" : "article-journal", "volume" : "60" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(53)", "plainTextFormattedCitation" : "(53)", "previouslyFormattedCitation" : "(53)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(53).The Quality of pain, a subjective description provided by the patient, may hint at the type of pain they are experiencing. For example, pain described as burning, “pins and needles” feeling, etc. may be indicative of neuropathic pain, which may be under evaluated/treated in CP patientsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1177/2049463713479230", "ISSN" : "2049-4637", "PMID" : "26516493", "abstract" : "The pain of chronic pancreatitis represents a major challenge to those working in the field, including pain specialists, gastroenterologists and surgeons. This article describes the different aetiologies of chronic pancreatitis and lists the models for the pathogenesis of pain, including novel ideas such as the role of the immune system in the modulation of pain. The patient profile in chronic pancreatitis is discussed along with the social impact of the disease in relation to alcohol misuse. The range of treatment strategies including medical, endoscopic and surgical approaches are evaluated. Common analgesic regimes and their limitations are reviewed. The pain of chronic pancreatitis remains refractory to effective treatment in many cases and further study and understanding of the underlying pathophysiology are required.", "author" : [ { "dropping-particle" : "", "family" : "Goulden", "given" : "Michael R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "British Journal of Pain", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2013", "2" ] ] }, "note" : "NULL", "page" : "8-22", "title" : "The pain of chronic pancreatitis: a persistent clinical challenge", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(47)", "plainTextFormattedCitation" : "(47)", "previouslyFormattedCitation" : "(47)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(47). Pain described as squeezing, pressure, cramping, distention, dull, deep, and stretching is usually visceral in origin. Visceral pain is most commonly recognized in CP patients, with pain that emanates from the viscera, is diffuse and difficult to localize and involves intense motor and autonomic reactions. It is also important to evaluate both the severity and quality of pain not only at rest or during a crisis, but to query these dimensions having the participant reference when they are standing, laying down, during movement, when using the bathroom and on palpation of the abdomen.Associated/Aggravating/Alleviating factors. Frequently diarrhea, nausea and vomiting accompany pain in CP, particularly breakthrough pain. Understanding what symptoms are associated with pain and when they occur in relation to pain, and what factors make it worse or improve it may bring insight into appropriate treatment recommendations. For example, if dietary, or other lifestyle factors play a role in aggravating symptoms, these would be a good place to start. Avoiding alcohol consumption, smoking and reducing fatty food consumption may all improve pain in CP (see treatment sections within these guidelines). Stress and anxiety frequently impact pain and patients who experience this connection may benefit from stress-reduction strategies or psychological interventions aimed at reducing such qualities. Similarly, factors that reduce pain should be queried, such as application of heat, relaxation, distraction, etc. as they could potentially be applied early in a flare.If alcohol issues are noted, it is warranted to delve deeper into the specifics of alcohol use, given the association between alcohol consumption and CP. If current alcohol use is endorsed or suspected, conducting a CAGE questionnaire (asking 1) have you felt the need to Cut down on your drinking?; 2) Have people Annoyed you by criticizing your drinking?; 3) Have you ever felt Guilty about drinking?; 4) Have you ever felt the need for an “Eye-opener” – a drink first thing in the morning to steady your nerves or get rid of a hangover) may aid in screening for problematic drinking behaviour. Mood is another important factor to consider and assess in CP. CP patients endorse significant difficulties in mood, social and emotional functioning. Depressive symptoms have been related to participants' reports of increased pain and decreased quality of life, with recent work suggesting that greater than half of CP patients may score above the cutoff for clinically significant depressive symptomologyADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1155/2012/978646", "ISSN" : "2090-1550", "PMID" : "23227332", "abstract" : "Objective. The present study was conducted to determine if depressive symptoms were associated with variability in pain perception and quality of life among patients with nonalcohol-related chronic pancreatitis. Methods. The research design was cross-sectional, and self-report data was collected from 692 patients with nonalcohol-related, intractable pancreatitis. The mean age of the sample was 52.6 (SD = 14.7); 41% of the sample were male. Participants completed the MOS SF12 Quality of Life Measure, the Center for Epidemiological Studies 10-item Depression Scale (CESD), and a numeric rating scale measure of \"pain on average\" from the Brief Pain Inventory. Results. Depressive symptoms were significantly related to participants' reports of increased pain and decreased quality of life. The mean CESD score of the sample was 10.6 (SD = 6.5) and 52% of the sample scored above the clinical cutoff for the presence of significant depressive symptomology. Patients scoring above the clinical cutoff on the depression screening measure rated their pain as significantly higher than those below the cutoff (P < 0.0001) and had significantly lower physical quality of life (P < 0.0001) and lower mental quality of life (P < 0.0001). Conclusion. Although causality cannot be determined based on cross-sectional, correlational data, findings suggest that among patients with nonalcoholic pancreatitis, the presence of depressive symptoms is common and may be a risk factor associated with increased pain and decreased quality of life. Thus, routine screening for depressive symptomology among patients with nonalcoholic pancreatitis may be warranted.", "author" : [ { "dropping-particle" : "", "family" : "Balliet", "given" : "Wendy E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Edwards-Hampton", "given" : "Shenelle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borckardt", "given" : "Jeffery J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morgan", "given" : "Katherine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adams", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Owczarski", "given" : "Stefanie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Madan", "given" : "Alok", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Galloway", "given" : "Sarah K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Serber", "given" : "Eva R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Malcolm", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pain research and treatment", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "978646", "title" : "Depressive Symptoms, Pain, and Quality of Life among Patients with Nonalcohol-Related Chronic Pancreatitis.", "type" : "article-journal", "volume" : "2012" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(54)", "plainTextFormattedCitation" : "(54)", "previouslyFormattedCitation" : "(54)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(54), which potentially warrants psychological evaluation and treatment. Of interest, they also found that clinically significant depression was strongly associated with greater pain severity and reduced physical and mental quality of life. While stress is a well-documented factor in flare ups, little research has focused on the role of anxiety or its relationship to pain or quality of life in CP. Pain catastrophizing, a negative cognitive and affective processes related to pain, characterized by helplessness, magnification and rumination about pain symptoms, is a risk factor for long-term pain and disproportionately-negative sequelae of pain (e.g., high levels of physical disability or healthcare costs)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/art.21865", "ISSN" : "0004-3591", "PMID" : "16583384", "abstract" : "OBJECTIVE Pain is among the most frequently reported, bothersome, and disabling symptoms described by patients with osteoarthritis, rheumatoid arthritis, fibromyalgia, and other musculoskeletal conditions. This review describes a growing body of literature relating catastrophizing, a set of cognitive and emotional processes encompassing magnification of pain-related stimuli, feelings of helplessness, and a generally pessimistic orientation, to the experience of pain and pain-related sequelae across several rheumatic diseases. METHODS We reviewed published articles in which pain-related catastrophizing was assessed in the context of one or more rheumatic conditions. Because much of the available information on catastrophizing is derived from the more general chronic pain literature, seminal studies in other disease states were also considered. RESULTS Catastrophizing is positively related, in both cross-sectional and prospective studies across different musculoskeletal conditions, to the reported severity of pain, affective distress, muscle and joint tenderness, pain-related disability, poor outcomes of pain treatment, and, potentially, to inflammatory disease activity. Moreover, these associations generally persist after controlling for symptoms of depression. There appear to be multiple mechanisms by which catastrophizing exerts its harmful effects, from maladaptive influences on the social environment to direct amplification of the central nervous system's processing of pain. CONCLUSION Catastrophizing is a critically important variable in understanding the experience of pain in rheumatologic disorders as well as other chronic pain conditions. Pain-related catastrophizing may be an important target for both psychosocial and pharmacologic treatment of pain.", "author" : [ { "dropping-particle" : "", "family" : "Edwards", "given" : "Robert R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bingham", "given" : "Clifton O.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bathon", "given" : "Joan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haythornthwaite", "given" : "Jennifer A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis & Rheumatism", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2006", "4", "15" ] ] }, "note" : "NULL", "page" : "325-332", "title" : "Catastrophizing and pain in arthritis, fibromyalgia, and other rheumatic diseases", "type" : "article-journal", "volume" : "55" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(55)", "plainTextFormattedCitation" : "(55)", "previouslyFormattedCitation" : "(55)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(55) in a variety of clinical pain conditions. Catastrophizing has been implicated as an etiologic or prognostic factor in a number of persistent painADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0304-3959", "PMID" : "11790476", "abstract" : "Biopsychosocial models of chronic pain hypothesize a role for psychological and environmental factors in adjustment to chronic pain. To test the utility of such models for understanding phantom limb pain, 61 persons with recent amputations were administered measures of average phantom limb pain intensity, pain interference, depression, pain coping use, pain cognitions and appraisals, and social environmental variables 1 month post-amputation, and the measures of pain intensity, pain interference, and depression again 5 months later. Multiple regression analyses showed that the psychosocial predictors made a statistically significant contribution to the concurrent prediction of average phantom limb pain, pain interference, and depression at the initial assessment, and a significant contribution to the prediction of subsequent change in pain interference and depression over the course of 5 months. The results support the utility of studying phantom limb pain from a biopsychosocial perspective, and identify specific biopsychosocial factors (e.g., catastrophizing cognitions, social support, solicitous responses from family members, and resting as a coping response) that may play an important role in adjustment to phantom limb pain.", "author" : [ { "dropping-particle" : "", "family" : "Jensen", "given" : "Mark P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ehde", "given" : "Dawn M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoffman", "given" : "Amy J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Patterson", "given" : "David R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Czerniecki", "given" : "Joseph M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Robinson", "given" : "Lawrence R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pain", "id" : "ITEM-1", "issue" : "1-2", "issued" : { "date-parts" : [ [ "2002", "1" ] ] }, "note" : "NULL", "page" : "133-42", "title" : "Cognitions, coping and social environment predict adjustment to phantom limb pain.", "type" : "article-journal", "volume" : "95" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.jpain.2007.05.007", "ISSN" : "1526-5900", "PMID" : "17631056", "abstract" : "UNLABELLED Because of a lack of evidence to support any treatment for phantom limb pain (PLP), interest has turned to preventing it instead. However, like other areas of PLP research, there is little consensus regarding factors that may be associated with the development of PLP. This study was devised to identify physical and psychological factors associated with PLP development and maintenance. It was a prospective study of 59 patients listed for amputation of a lower limb due to peripheral vascular disease. Each was interviewed before amputation, and the survivors were reinterviewed 6 months afterward. Pain and coping style were the primary outcome measures. The use of high levels of passive coping strategies (P = .001), especially catastrophizing (P = .02) before amputation, were found to be associated with PLP development. Pain was only weakly associated with the presence of PLP 6 months after amputation. The ability to move the phantom (P = .01) and stump pain (P = .01) were postamputation factors associated with PLP. The complexity of the relationship between previous pain and coping style and the development of PLP is discussed alongside aspects of pain memory. Pre-emptive treatment of PLP will need to include psychological as well as physical interventions. PERSPECTIVE During this study, preamputation passive coping (especially catastrophizing) was found to be associated with the development of PLP. This knowledge will help researchers and clinicians to identify future targets for pre-emption of this condition because once established, PLP is difficult to treat.", "author" : [ { "dropping-particle" : "", "family" : "Richardson", "given" : "Cliff", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Glenn", "given" : "Sheila", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Horgan", "given" : "Maureen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nurmikko", "given" : "Turo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The journal of pain : official journal of the American Pain Society", "id" : "ITEM-2", "issue" : "10", "issued" : { "date-parts" : [ [ "2007", "10" ] ] }, "note" : "NULL", "page" : "793-801", "title" : "A prospective study of factors associated with the presence of phantom limb pain six months after major lower limb amputation in patients with peripheral vascular disease.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISSN" : "0002-9262", "PMID" : "12446259", "abstract" : "By using a population-based cohort of the general Dutch population, the authors studied whether an excessively negative orientation toward pain (pain catastrophizing) and fear of movement/(re)injury (kinesiophobia) are important in the etiology of chronic low back pain and associated disability, as clinical studies have suggested. A total of 1,845 of the 2,338 inhabitants (without severe disease) aged 25-64 years who participated in a 1998 population-based questionnaire survey on musculoskeletal pain were sent a second questionnaire after 6 months; 1,571 (85 percent) participated. For subjects with low back pain at baseline, a high level of pain catastrophizing predicted low back pain at follow-up (odds ratio (OR) = 1.7, 95% confidence interval (CI): 1.0, 2.8) and chronic low back pain (OR = 1.7, 95% CI: 1.0, 2.3), in particular severe low back pain (OR = 3.0, 95% CI: 1.7, 5.2) and low back pain with disability (OR = 3.0, 95% CI: 1.7, 5.4). A high level of kinesiophobia showed similar associations. The significant associations remained after adjustment for pain duration, pain severity, or disability at baseline. For those without low back pain at baseline, a high level of pain catastrophizing or kinesiophobia predicted low back pain with disability during follow-up. These cognitive and emotional factors should be considered when prevention programs are developed for chronic low back pain and related disability.", "author" : [ { "dropping-particle" : "", "family" : "Picavet", "given" : "H Susan J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vlaeyen", "given" : "Johan W S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schouten", "given" : "Jan S A G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American journal of epidemiology", "id" : "ITEM-3", "issue" : "11", "issued" : { "date-parts" : [ [ "2002", "12", "1" ] ] }, "note" : "NULL", "page" : "1028-34", "title" : "Pain catastrophizing and kinesiophobia: predictors of chronic low back pain.", "type" : "article-journal", "volume" : "156" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1016/j.jclinepi.2006.11.012", "ISSN" : "0895-4356", "PMID" : "17606181", "abstract" : "OBJECTIVE To investigate the clinical course and prognostic factors of complaints of arm, neck, and shoulder. STUDY DESIGN AND SETTING A prospective cohort study in physical therapy practice. Participating physiotherapists recruited new consulters with musculoskeletal complaints of the neck and/or upper extremities. Participants filled in questionnaires at baseline, 3 months, and 6 months. The main outcome measure was the persistence of complaints over 6-month follow-up. Possible predictors like social and psychological factors, physical factors, and complaint specific factors were tested in univariate and multivariate logistic regression analyses for repeated measurements. RESULTS Of the 624 participants at baseline 543 (87%) returned at least one follow-up questionnaire. At 6-month follow-up, 40% had persisting pain and discomfort. Somatization, kinesiophobia, catastrophizing, and a long duration of complaints at baseline were significantly related to the persistence of complaints over 6 months in the total population. In those with paid work (77%), catastrophizing, low decision authority at work, and a long duration of complaints at baseline were significantly related to the persistence of complaints over 6 months. CONCLUSION 40% of the participants had persisting pain and discomfort after 6 months and mainly social and psychological factors played a role in this course.", "author" : [ { "dropping-particle" : "", "family" : "Karels", "given" : "C H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bierma-Zeinstra", "given" : "S M A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burdorf", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Verhagen", "given" : "A P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nauta", "given" : "A P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koes", "given" : "B W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of clinical epidemiology", "id" : "ITEM-4", "issue" : "8", "issued" : { "date-parts" : [ [ "2007", "8" ] ] }, "note" : "NULL", "page" : "839-48", "title" : "Social and psychological factors influenced the course of arm, neck and shoulder complaints.", "type" : "article-journal", "volume" : "60" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1007/s10926-007-9109-9", "ISSN" : "1053-0487", "PMID" : "17973181", "abstract" : "OBJECTIVES Knowledge regarding the working mechanism of an intervention is essential for obtaining a better understanding of the intervention and contributes to optimize its outcome. This study aimed at investigating whether changes in cognitive-behavioral factors and muscle activation patterns after myofeedback training and ergonomic counseling were associated with outcome, in subjects with work-related musculoskeletal neck-shoulder complaints. METHODS Seventy-nine symptomatic subjects received either myofeedback with ergonomic counseling (Mfb/EC) or ergonomic counseling alone (EC). Outcome measures discomfort and disability, and process factors catastrophizing, pain control, fear-avoidance beliefs, and muscle activation patterns were assessed at baseline, after the interventions (T0), and at 3 months follow-up (T3). Mixed modeling techniques were used for analysis. RESULTS Outcome in terms of discomfort and disability was generally comparable between both interventions. Catastrophizing was significantly reduced and fear-avoidance beliefs about work slightly increased after the interventions, but no consistent changes in muscle activation patterns were observed. Changes in discomfort were especially associated with changes in catastrophizing at T0 and T3, but R(2) was low (<0.14). Reduced catastrophizing at T0 and T3, and also reduced fear-avoidance beliefs about work at T3, were related to reduced disability (R(2) between 0.30 and 0.40). No differences between the two intervention groups were observed. CONCLUSIONS Intervention effects were generally non-specific and findings suggested that cognitive-behavioral factors underlie the outcome of these interventions rather than changes in muscle activation patterns. Emphasizing these factors during therapy may increase the beneficial outcome of occupational interventions.", "author" : [ { "dropping-particle" : "", "family" : "Voerman", "given" : "Gerlienke E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandsj\u00f6", "given" : "Leif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vollenbroek-Hutten", "given" : "Miriam M R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Larsman", "given" : "Pernilla", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kadefors", "given" : "Roland", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hermens", "given" : "Hermie J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of occupational rehabilitation", "id" : "ITEM-5", "issue" : "4", "issued" : { "date-parts" : [ [ "2007", "12", "13" ] ] }, "note" : "NULL", "page" : "593-609", "title" : "Changes in cognitive-behavioral factors and muscle activation patterns after interventions for work-related neck-shoulder complaints: relations with discomfort and disability.", "type" : "article-journal", "volume" : "17" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1097/AJP.0b013e3181468e67", "ISSN" : "0749-8047", "PMID" : "17885347", "abstract" : "OBJECTIVES This study evaluated predictors of poor outcome in patients with neck pain treated by physical therapy, and sought to compare the findings of empirical data with physical therapy practitioners' subjective perceptions about predictors of outcome. METHODS This study was a secondary analysis of data from a randomized controlled trial assessing physical therapy treatments for neck pain (n=346). A baseline questionnaire provided data on a number of potential risk factors of poor outcome at follow-up. Follow-up was conducted at 6 weeks and 6 months by postal questionnaire with outcome defined separately by perceived (global) change and minimal clinically important differences in the Northwick Park Neck Pain Questionnaire (MCID-NPQ). Therapists' perceptions of predictors for treatment outcome were captured using a separate questionnaire, and the ratings compared with ranks derived from the 6-month trial data. RESULTS Baseline characteristics accounted for a much greater proportion of explained variance for global change compared with MCID-NPQ at 6 months. Independent biopsychosocial characteristics included manual social class, catastrophizing, anxiety and depression, low treatment expectations, severity of baseline neck pain/disability, presence of comorbid back pain, and older age. Physical therapist ranks correlated highly with those derived from the trial data. CONCLUSIONS Significant predictors of outcome were identified, particularly at 6 months, including psychosocial, functional, and demographic indicators. Our findings suggest that physical therapists are collectively aware of the relative importance of physical and psychosocial factors in predicting clinical outcome. However, a significant amount of variability in outcomes in our prognostic models remained largely unexplained, indicating that we need to explore further underlying factors to inform clinical decision-making.", "author" : [ { "dropping-particle" : "", "family" : "Hill", "given" : "Jonathan C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lewis", "given" : "Martyn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sim", "given" : "Julius", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hay", "given" : "Elaine M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dziedzic", "given" : "Krysia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Clinical journal of pain", "id" : "ITEM-6", "issue" : "8", "issued" : { "date-parts" : [ [ "2007", "10" ] ] }, "note" : "NULL", "page" : "683-90", "title" : "Predictors of poor outcome in patients with neck pain treated by physical therapy.", "type" : "article-journal", "volume" : "23" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(56\u201361)", "plainTextFormattedCitation" : "(56\u201361)", "previouslyFormattedCitation" : "(56\u201361)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(56–61), higher pain and disability following surgeryADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jhsa.2007.11.025", "ISSN" : "0363-5023", "PMID" : "18343281", "abstract" : "PURPOSE To test the null hypothesis that depression does not correlate with patient satisfaction after open release of electrodiagnostically confirmed carpal tunnel syndrome when controlling for other demographic, disease-related, and psychosocial factors. METHODS Eighty-two survey respondents who had recovered (minimum 2 years after surgery) from a limited incision open carpal tunnel release completed measures of satisfaction, perceived disability, depression, pain catastrophizing, and pain anxiety. Univariate and multivariate analyses sought predictors of satisfaction and perceived disability from among demographic, disease related, and psychological factors. RESULTS The average satisfaction score was 8 points (range, 0-10) and the average Disabilities of the Arm, Shoulder, and Hand score was 13 points (range, 0-76). Predictors of greater dissatisfaction included greater depression and the categorical electrophysiologic test rating. Predictors of perceived disability included depression, pain catastrophizing, and static numbness. Depression was the dominant predictor of both satisfaction and perceived disability. CONCLUSIONS Dissatisfaction and perceived disability after limited open carpal tunnel release for electrodiagnostically confirmed idiopathic carpal tunnel syndrome is predicted primarily by depression and ineffective coping skills and to a lesser degree by clinical or electrophysiologic evidence of advanced nerve damage. TYPE OF STUDY/LEVEL OF EVIDENCE Prognostic II.", "author" : [ { "dropping-particle" : "", "family" : "Lozano Calder\u00f3n", "given" : "Santiago A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Paiva", "given" : "Alex", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ring", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of hand surgery", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2008", "3" ] ] }, "note" : "NULL", "page" : "303-7", "title" : "Patient satisfaction after open carpal tunnel release correlates with depression.", "type" : "article-journal", "volume" : "33" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0749-8047", "PMID" : "16093750", "abstract" : "OBJECTIVES This study was a prospective investigation of the extent to which psychologic variables could be predictive of postoperative pain. Study aims were: 1) to evaluate whether an assessment of pre-operative distress factors could predict the intensity of postoperative pain; and 2) to characterize the unique pattern in which anxiety and pain catastrophizing scores relate to postoperative pain. METHODS The Pain Catastrophizing Scale and the State-Trait Anxiety Inventory were administered to 38 patients scheduled for elective abdominal surgery. The questionnaires were completed on the day of admission, a day before the operation. On day 1 and day 2 following the operation, perception of pain intensity at the surgical wound was assessed by visual analog scale. RESULTS The Pain Catastrophizing Scale and State-Trait Anxiety Inventory scores were significantly correlated with the postoperative pain scores. A linear regression analysis showed that Pain Catastrophizing Scale predicted the level of postoperative pain intensity even after controlling for state anxiety and that trait anxiety was not a significant predictor. In addition, analysis of the unique pattern of each predictor related to postoperative pain intensity indicated a linear curve for the Pain Catastrophizing Scale and curvilinear curve for the state anxiety. DISCUSSION The results are discussed in light of appraisal and coping theories. It is suggested that a simple assessment of preoperative catastrophizing tendency and anxiety scores may assist medical teams in postoperative pain management.", "author" : [ { "dropping-particle" : "", "family" : "Granot", "given" : "Michal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferber", "given" : "Sari Goldstein", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Clinical journal of pain", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "0" ] ] }, "note" : "NULL", "page" : "439-45", "title" : "The roles of pain catastrophizing and anxiety in the prediction of postoperative pain intensity: a prospective study.", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.jpain.2006.09.004", "ISSN" : "1526-5900", "PMID" : "17113350", "abstract" : "UNLABELLED This prospective study assessed the relation between pain catastrophizing, response to experimental pain stimuli, and pain perceived by women after elective cesarean sections. Forty-seven women who were scheduled for elective cesarean section were enrolled in the study. Magnitude estimation to suprathreshold phasic and tonic heat pain stimuli was assessed 1 or 2 days before surgery. Women completed the Pain Catastrophizing Scale after the heat stimuli and again on the first postoperative day. During the first and second postoperative days, perception of pain intensity was assessed by visual analog scale at each analgesia request. A multiple regression analysis revealed that pain on the first postoperative day was predicted by patient response to preoperative tonic heat stimuli (r(2) = .167, P = .008). Pain on the second postoperative day was predicted by preoperative pain catastrophizing (r(2) = .139, P = .021). No significant association was observed between preoperative response to heat stimuli or pain catastrophizing and the patient's analgesic consumption in the obstetrical ward. It is concluded that pain catastrophizing and response to experimental tonic heat pain correlate with post-cesarean section pain. PERSPECTIVE This article presents psychological and psychophysical measures that may be of help in the prediction of post-cesarean section pain. It may therefore contribute to the treatment of the sequelae of the most common major surgical procedure performed in women in their reproductive years.", "author" : [ { "dropping-particle" : "", "family" : "Strulov", "given" : "Lihi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zimmer", "given" : "Etan Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Granot", "given" : "Michal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tamir", "given" : "Ada", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jakobi", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lowenstein", "given" : "Lior", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The journal of pain : official journal of the American Pain Society", "id" : "ITEM-3", "issue" : "3", "issued" : { "date-parts" : [ [ "2007", "3" ] ] }, "note" : "NULL", "page" : "273-9", "title" : "Pain catastrophizing, response to experimental heat stimuli, and post-cesarean section pain.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "ISSN" : "0160-7715", "PMID" : "8932659", "abstract" : "This study investigated the relation of cognitive coping and catastrophizing to acute postoperative pain and analgesic use. Fifty-nine women who had just undergone breast cancer surgery rated their pain on 3 consecutive days and completed a self-report measure of cognitive coping and catastrophizing prior to hospital discharge. Analgesic use over the 3-day period was tabulated from pharmacy records. Based on prior research, it was hypothesized that increased catastrophizing and decreased use of cognitive coping strategies would be associated with greater pain and analgesic use. Results partially confirmed these hypotheses. Catastrophizing, but not cognitive coping, was associated with individual differences in pain intensity and analgesic use. Additional analyses indicated that age was a significant predictor of both catastrophizing and postoperative pain. Specifically, younger patients were more likely to catastrophize and to report increased postoperative pain. Theoretical and clinical implications of these findings are discussed.", "author" : [ { "dropping-particle" : "", "family" : "Jacobsen", "given" : "P B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Butler", "given" : "R W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of behavioral medicine", "id" : "ITEM-4", "issue" : "1", "issued" : { "date-parts" : [ [ "1996", "2" ] ] }, "note" : "NULL", "page" : "17-29", "title" : "Relation of cognitive coping and catastrophizing to acute pain and analgesic use following breast cancer surgery.", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(62\u201365)", "plainTextFormattedCitation" : "(62\u201365)", "previouslyFormattedCitation" : "(62\u201365)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(62–65), longer recovery timesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1348/135910701169043", "ISSN" : "1359-107X", "PMID" : "14596737", "abstract" : "OBJECTIVE To identify the psychological factors that predict short-term recovery following total knee replacement. METHOD A group of 42 patients undergoing total knee replacement received a pre-operative psychological assessment. Four self-report questionnaires were completed: the Pain Coping Strategies Questionnaire; the Short Form Social Support Questionnaire; the Recovery Locus of Control Scale; and the Brief Symptom Inventory. Post-operative outcome was assessed in terms of the number of days taken to achieve key physiotherapy milestones (straight leg raise; 90 degrees bend of the knee) and discharge. RESULTS The three response variables were analysed separately using an ordinal regression. Internal locus of control was associated with a shorter time to achieve a straight leg raise. Larger values of catastrophizing were associated with longer times to achieve a 90 degrees bend. There was a trend towards larger values of satisfaction with social support to be associated with an earlier achievement of the 90 degrees bend. No psychological variables were found to be associated with the length of hospital stay. CONCLUSIONS As suggested by previous studies, coping style and locus of control appear to be important in the rehabilitation process. The current data suggest that psychological variables could be usefully included in a pre-operative assessment for total knee replacement.", "author" : [ { "dropping-particle" : "", "family" : "Kendell", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saxby", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Farrow", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Naisby", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "British journal of health psychology", "id" : "ITEM-1", "issue" : "Pt 1", "issued" : { "date-parts" : [ [ "2001", "2" ] ] }, "note" : "NULL", "page" : "41-52", "title" : "Psychological factors associated with short-term recovery from total knee replacement.", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(66)", "plainTextFormattedCitation" : "(66)", "previouslyFormattedCitation" : "(66)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(66), and less improvement in painADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1053/eujp.2000.0165", "ISSN" : "1090-3801", "PMID" : "10957696", "abstract" : "In this study, 54 patients suffering from chronic cervicobrachialgia (mean pain duration 7 years) were treated with radiofrequency lesioning of the cervical spinal dorsal root ganglion (RF-DRG). The aim of the study was to investigate whether psychological variables would be predictive for the changes in pain intensity after medical treatment. The following psychological aspects were measured: pain cognitions, negative self-efficacy and catastrophizing, physical and psychosocial dysfunction, and overall distress. The level of catastrophizing before treatment appeared to predict 10% of the changes in pain intensity after treatment. Changes in pain intensity after RF-DRG were positively correlated with changes in psychosocial dysfunction and negative self-efficacy.", "author" : [ { "dropping-particle" : "", "family" : "Samwel", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slappendel", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crul", "given" : "B J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voerman", "given" : "V F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European journal of pain (London, England)", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2000", "6" ] ] }, "note" : "NULL", "page" : "149-55", "title" : "Psychological predictors of the effectiveness of radiofrequency lesioning of the cervical spinal dorsal ganglion (RF-DRG).", "type" : "article-journal", "volume" : "4" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(67)", "plainTextFormattedCitation" : "(67)", "previouslyFormattedCitation" : "(67)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(67). Thus, catastrophizing may well be an important prognostic factor in CP, but a dearth of information exists in regards to catastrophizing in CP patients.The impact on quality of life is also important to evaluate and is clearly important in patients with CPADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/gut.2010.236620", "ISSN" : "1468-3288", "PMID" : "21610272", "abstract" : "OBJECTIVE In patients with painful chronic pancreatitis (CP) there is increasing evidence of abnormal pain processing in the central nervous system. Using magnetic resonance (MR) diffusion tensor imaging, brain microstructure in areas involved in processing of visceral pain was characterised and these findings were correlated to clinical pain scores. METHODS 23 patients with CP pain and 14 controls were studied in a 3T MR scanner. Apparent diffusion coefficient (ADC) (ie, diffusivity of water) and fractional anisotropy (FA) (ie, organisation of fibres) values were assessed in the amygdala, cingulate cortex, insula, prefrontal cortex and secondary sensory cortex. Daily pain scores and the Brief Pain Inventory Short Form were collected 1 week before the investigation. RESULTS In grey matter, patients had increased ADC values in amygdala, cingulate cortex, insula and prefrontal cortex, as well as decreased FA values in cingulate cortex and secondary sensory cortex. In white matter, patients had increased ADC values in insula and prefrontal cortex, and decreased FA values in insula and prefrontal cortex (all p values <0.05). An effect modification from the pain pattern (attacks vs continuous pain) was seen in the insula and secondary sensory cortex (p values <0.05), but no effect modifications from diabetes, alcoholic aetiology and opioid treatment were seen (all p values >0.05). Microstructural changes in cingulate and prefrontal cortices were correlated to patients' clinical pain scores. CONCLUSION The findings suggest that microstructural changes of the brain accompany pain in CP. The changes are likely to be a consequence of ongoing pain and structural reorganisation of the neuromatrix as also seen in other diseases characterised by chronic pain.", "author" : [ { "dropping-particle" : "", "family" : "Fr\u00f8kj\u00e6r", "given" : "Jens Br\u00f8ndum", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olesen", "given" : "S\u00f8ren Schou", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gram", "given" : "Mikkel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yavarian", "given" : "Yousef", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bouwense", "given" : "Stefan A W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "Oliver H G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn Mohr", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gut", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2011", "11", "1" ] ] }, "page" : "1554-62", "title" : "Altered brain microstructure assessed by diffusion tensor imaging in patients with chronic pancreatitis.", "type" : "article-journal", "volume" : "60" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.pan.2014.09.009", "ISSN" : "1424-3911", "PMID" : "25455540", "abstract" : "BACKGROUND/OBJECTIVES Chronic pancreatitis (CP) is a disabling disease characterised by abdominal pain, and various pancreatic and extra-pancreatic complications. We investigated the interactions between pain characteristics (i.e. pain severity and its pattern in time), complications, and quality of life (QOL) in patients with CP. METHODS This was a cross-sectional study of 106 patients with CP conducted at two North European tertiary medical centres. Detailed information on clinical patient characteristics was obtained from interviews and through review of the individual patient records. Pain severity scores and pain pattern time profiles were extracted from the modified brief pain inventory short form and correlated to QOL as assessed by the EORTC QLQ-C30 questionnaire. Interactions with exocrine and endocrine pancreatic insufficiency, as well as pancreatic and extra-pancreatic complications were analysed using regression models. RESULTS Pain was the most prominent symptom in our cohort and its severity was significantly correlated with EORTC global health status (r = -0.46; P < 0.001) and most functional and symptom subscales. In contrast the patterns of pain in time were not associated with any of the life quality subscales. When controlling for interactions from exocrine and endocrine pancreatic insufficiency no effect modifications were evident (P = 0.72 and P = 0.85 respectively), while the presence of pancreatic and extra-pancreatic complications was associated with an almost 15% decrease in life quality (P = 0.004). CONCLUSIONS Pain severity and disease related complications significantly reduce life quality in patients with CP. This information is important in order to design more accurate and clinical meaningful endpoints in future outcome trials.", "author" : [ { "dropping-particle" : "", "family" : "Olesen", "given" : "S\u00f8ren Schou", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Juel", "given" : "Jacob", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nielsen", "given" : "Anders Klitgaard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fr\u00f8kj\u00e6r", "given" : "Jens Br\u00f8ndum", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "Oliver H G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn Mohr", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2014", "11" ] ] }, "note" : "NULL", "page" : "497-502", "title" : "Pain severity reduces life quality in chronic pancreatitis: Implications for design of future outcome trials.", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(13,68)", "plainTextFormattedCitation" : "(13,68)", "previouslyFormattedCitation" : "(13,68)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(13,68). Inquiring about changes in appetite, physical activity, relationships, family functioning/functioning within the household, sexual functioning, irritability, sleep, anxiety, anger, depression and concentration will aid in understanding the pain experience in each individual. A number of these factors have bidirectional relationships with pain which could represent modifiable risk factors that could be improved and reduce pain. Sleep for example, is well known to be disturbed by pain, but recent work also identifies sleep as an independent modulator of pain perception; thus disturbed sleep could exacerbate the following day’s pain creating a vicious cycleADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/pme.12231", "ISSN" : "1526-4637", "PMID" : "24102962", "abstract" : "OBJECTIVE Although poor sleep is a consequence of pain, sleep disturbance reciprocally induces hyperalgesia and exacerbates clinical pain. Conceptual models of chronic pain implicate dysfunctional supraspinal pain processing mechanisms, mediated in part by endogenous opioid peptides. Our preliminary work indicates that sleep disruption impairs psychophysical measures of descending pain modulation, but few studies have investigated whether insufficient sleep may be associated with alterations in endogenous opioid systems. This preliminary, exploratory investigation sought to examine the relationship between sleep and functioning of the cerebral mu opioid system during the experience of pain in healthy participants. SUBJECTS AND DESIGN Twelve healthy volunteers participated in a 90-minute positron emission tomography imaging scan using [11C]Carfentanil, a mu opioid receptors agonist. During the session, pain responses to a 10% topical capsaicin cream were continuously rated on a 0-100 scale. Participants also completed the Pittsburgh Sleep Quality Index (PSQI). RESULTS Poor sleep quality (PSQI) was positively and significantly associated with greater binding potential (BP) in regions within the frontal lobes. In addition, sleep duration was negatively associated with BP in these areas as well as the temporal lobe and anterior cingulate. CONCLUSIONS These findings suggest that poor sleep quality and short sleep duration are associated with endogenous opioid activity in these brain regions during the application of a noxious stimulus. Elucidating the role of the endogenous opioid system in mediating some of the associations between sleep and pain could significantly improve our understanding of the pathophysiology of chronic pain and might advance clinical practice by suggesting interventions that could buffer the adverse effects of poor sleep on pain.", "author" : [ { "dropping-particle" : "", "family" : "Campbell", "given" : "Claudia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bounds", "given" : "Sara C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuwabara", "given" : "Hiroto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Edwards", "given" : "Robert R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Campbell", "given" : "James N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haythornthwaite", "given" : "Jennifer A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Michael T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pain medicine (Malden, Mass.)", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2013", "12", "1" ] ] }, "page" : "1882-92", "title" : "individual variation in sleep quality and duration is related to cerebral mu opioid receptor binding potential during tonic laboratory pain in healthy subjects.", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.jpain.2013.08.007", "ISSN" : "1528-8447", "PMID" : "24290442", "abstract" : "UNLABELLED Ample evidence suggests that sleep and pain are related. However, many questions remain about the direction of causality in their association, as well as mechanisms that may account for their association. The prevailing view has generally been that they are reciprocally related. The present review critically examines the recent prospective and experimental literature (2005-present) in an attempt to update the field on emergent themes pertaining to the directionality and mechanisms of the association of sleep and pain. A key trend emerging from population-based longitudinal studies is that sleep impairments reliably predict new incidents and exacerbations of chronic pain. Microlongitudinal studies employing deep subjective and objective assessments of pain and sleep support the notion that sleep impairments are a stronger, more reliable predictor of pain than pain is of sleep impairments. Recent experimental studies suggest that sleep disturbance may impair key processes that contribute to the development and maintenance of chronic pain, including endogenous pain inhibition and joint pain. Several biopsychosocial targets for future mechanistic research on sleep and pain are discussed, including dopamine and opioid systems, positive and negative affect, and sociodemographic factors. PERSPECTIVE This critical review examines the recent prospective and experimental research (2005-present) on the association of sleep and pain in an attempt to identify trends suggestive of directionality and potential mechanisms. An update on this literature is needed to guide future clinical efforts to develop and augment treatments for chronic sleep disturbance and chronic pain.", "author" : [ { "dropping-particle" : "", "family" : "Finan", "given" : "Patrick H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goodin", "given" : "Burel R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Michael T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The journal of pain : official journal of the American Pain Society", "id" : "ITEM-2", "issue" : "12", "issued" : { "date-parts" : [ [ "2013", "12" ] ] }, "page" : "1539-52", "title" : "The association of sleep and pain: an update and a path forward.", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(69,70)", "plainTextFormattedCitation" : "(69,70)", "previouslyFormattedCitation" : "(69,70)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(69,70). In order to evaluate the impact of pain on patients’ quality of life, the EORTC QLQ-C30 and QLZQ-PAN26 questionnaires have been formally examined and validated for CP patientsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1572-0241.2005.40859.x", "ISSN" : "0002-9270", "PMID" : "15784041", "abstract" : "BACKGROUND AND AIMS Chronic pancreatitis (CP) produces disabling symptoms and requires major clinical interventions over a number of years. There is consensus that quality-of-life (QoL) assessment should be part of assessing the treatment and outcome of CP. These symptoms and treatments resemble those of pancreatic cancer, for which there are validated QoL assessment instruments. The aim of our study was to assess the appropriateness of using the EORTC QoL assessment system for pancreatic cancer (the EORTC QLQ-C30 and QLQ-PAN26) for patients with CP, and to document important issues that affect QoL in these patients. METHODS A structured literature review was undertaken to determine current approaches to QoL in pancreatic disease. Sixty-six patients with newly diagnosed or treated CP were asked to complete the EORTC QLQ-C30 and QLQ-PAN26 in four countries (Germany, Italy, South Africa, and United Kingdom). Patients were asked to review the appropriateness of the content and structure of the instruments, during a directed interview. Standard psychometric tests were used to assess the reliability and validity of the instruments. Peer review was undertaken to review findings and adapt the QLQ-PAN26 on the basis of the responses obtained. RESULTS The literature review highlighted the potential value of the EORTC QLQ-C30 and identified the lack of a CP-specific instrument, which had been appropriately developed. There was overwhelming consensus among experts that the EORTC assessment system appeared suitable for use in CP patients. This was endorsed by all patients. Patients identified additional issues related to guilt about the use of alcohol and the burden of trying to abstain. All but one scale (jaundice) exhibited adequate internal consistency (r > 0.70) Construct validity of the QLQ-C30 and QLQ-PAN26 showed strong associations between conceptually related scales (r > 0.6, p < 0.001) and significantly discriminated between patients on the basis of performance status and requirement for opiate analgesia. Significant issues affecting QoL in CP patients, in addition to recognized symptoms of the disease, were fear of future health problems, difficulty sleeping, and fatigue. CONCLUSION The EORTC QLQ-C30 and QLQ-PAN26 appear to be an appropriate assessment system for CP, with the addition of items to cover guilt about alcohol consumption, and the burden of abstention. Patients' QoL is adversely affected by the fear of future health problems, difficulty sleep\u2026", "author" : [ { "dropping-particle" : "", "family" : "Fitzsimmons", "given" : "Deborah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kahl", "given" : "Stefan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Butturini", "given" : "Giovanni", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wyk", "given" : "Marc", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bornman", "given" : "Phillipus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bassi", "given" : "Claudio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Malfertheiner", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "George", "given" : "Steve L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Colin D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American journal of gastroenterology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2005", "4" ] ] }, "note" : "NULL", "page" : "918-26", "title" : "Symptoms and quality of life in chronic pancreatitis assessed by structured interview and the EORTC QLQ-C30 and QLQ-PAN26.", "type" : "article-journal", "volume" : "100" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(71)", "plainTextFormattedCitation" : "(71)", "previouslyFormattedCitation" : "(71)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(71). Central SensitizationPain processing occurs in the central nervous system, where nociceptive input can be inhibited or facilitated and which can undergo both functional and structural plasticityADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nm.2231", "ISSN" : "1078-8956", "PMID" : "20948531", "abstract" : "Chronic pain is a major challenge to clinical practice and basic science. The peripheral and central neural networks that mediate nociception show extensive plasticity in pathological disease states. Disease-induced plasticity can occur at both structural and functional levels and is manifest as changes in individual molecules, synapses, cellular function and network activity. Recent work has yielded a better understanding of communication within the neural matrix of physiological pain and has also brought important advances in concepts of injury-induced hyperalgesia and tactile allodynia and how these might contribute to the complex, multidimensional state of chronic pain. This review focuses on the molecular determinants of network plasticity in the central nervous system (CNS) and discusses their relevance to the development of new therapeutic approaches.", "author" : [ { "dropping-particle" : "", "family" : "Kuner", "given" : "Rohini", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature Medicine", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2010", "11", "14" ] ] }, "note" : "NULL", "page" : "1258-1266", "title" : "Central mechanisms of pathological pain", "type" : "article-journal", "volume" : "16" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(72)", "plainTextFormattedCitation" : "(72)", "previouslyFormattedCitation" : "(72)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(72). When plasticity results in amplification of pain, this central sensitization (CS) represents a rewiring that can include inhibition of descending pain modulation and/or changes in connectivityADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.pain.2010.09.030", "ISSN" : "0304-3959", "PMID" : "20961685", "abstract" : "Nociceptor inputs can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways, the phenomenon of central sensitization. Central sensitization manifests as pain hypersensitivity, particularly dynamic tactile allodynia, secondary punctate or pressure hyperalgesia, aftersensations, and enhanced temporal summation. It can be readily and rapidly elicited in human volunteers by diverse experimental noxious conditioning stimuli to skin, muscles or viscera, and in addition to producing pain hypersensitivity, results in secondary changes in brain activity that can be detected by electrophysiological or imaging techniques. Studies in clinical cohorts reveal changes in pain sensitivity that have been interpreted as revealing an important contribution of central sensitization to the pain phenotype in patients with fibromyalgia, osteoarthritis, musculoskeletal disorders with generalized pain hypersensitivity, headache, temporomandibular joint disorders, dental pain, neuropathic pain, visceral pain hypersensitivity disorders and post-surgical pain. The comorbidity of those pain hypersensitivity syndromes that present in the absence of inflammation or a neural lesion, their similar pattern of clinical presentation and response to centrally acting analgesics, may reflect a commonality of central sensitization to their pathophysiology. An important question that still needs to be determined is whether there are individuals with a higher inherited propensity for developing central sensitization than others, and if so, whether this conveys an increased risk in both developing conditions with pain hypersensitivity, and their chronification. Diagnostic criteria to establish the presence of central sensitization in patients will greatly assist the phenotyping of patients for choosing treatments that produce analgesia by normalizing hyperexcitable central neural activity. We have certainly come a long way since the first discovery of activity-dependent synaptic plasticity in the spinal cord and the revelation that it occurs and produces pain hypersensitivity in patients. Nevertheless, discovering the genetic and environmental contributors to and objective biomarkers of central sensitization will be highly beneficial, as will additional treatment options to prevent or reduce this prevalent and promiscuous form of pain plasticity.", "author" : [ { "dropping-particle" : "", "family" : "Woolf", "given" : "Clifford J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pain", "id" : "ITEM-1", "issue" : "Supplement", "issued" : { "date-parts" : [ [ "2011", "3" ] ] }, "note" : "NULL", "page" : "S2-S15", "title" : "Central sensitization: Implications for the diagnosis and treatment of pain", "type" : "article-journal", "volume" : "152" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(73)", "plainTextFormattedCitation" : "(73)", "previouslyFormattedCitation" : "(73)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(73), including changes to forebrain circuits involved in emotion and cognitionADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.pain.2014.07.021", "ISSN" : "1872-6623", "PMID" : "25083929", "author" : [ { "dropping-particle" : "", "family" : "Woolf", "given" : "Clifford J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pain", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2014", "10" ] ] }, "note" : "NULL", "page" : "1911-2", "title" : "What to call the amplification of nociceptive signals in the central nervous system that contribute to widespread pain?", "type" : "article-journal", "volume" : "155" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(74)", "plainTextFormattedCitation" : "(74)", "previouslyFormattedCitation" : "(74)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(74). Central sensitization is implicated as a mechanism of pain chronification (transition from acute to chronic pain), amplification, and maintenance in a number of chronic pain conditionsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.pain.2010.09.030", "ISSN" : "0304-3959", "PMID" : "20961685", "abstract" : "Nociceptor inputs can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways, the phenomenon of central sensitization. Central sensitization manifests as pain hypersensitivity, particularly dynamic tactile allodynia, secondary punctate or pressure hyperalgesia, aftersensations, and enhanced temporal summation. It can be readily and rapidly elicited in human volunteers by diverse experimental noxious conditioning stimuli to skin, muscles or viscera, and in addition to producing pain hypersensitivity, results in secondary changes in brain activity that can be detected by electrophysiological or imaging techniques. Studies in clinical cohorts reveal changes in pain sensitivity that have been interpreted as revealing an important contribution of central sensitization to the pain phenotype in patients with fibromyalgia, osteoarthritis, musculoskeletal disorders with generalized pain hypersensitivity, headache, temporomandibular joint disorders, dental pain, neuropathic pain, visceral pain hypersensitivity disorders and post-surgical pain. The comorbidity of those pain hypersensitivity syndromes that present in the absence of inflammation or a neural lesion, their similar pattern of clinical presentation and response to centrally acting analgesics, may reflect a commonality of central sensitization to their pathophysiology. An important question that still needs to be determined is whether there are individuals with a higher inherited propensity for developing central sensitization than others, and if so, whether this conveys an increased risk in both developing conditions with pain hypersensitivity, and their chronification. Diagnostic criteria to establish the presence of central sensitization in patients will greatly assist the phenotyping of patients for choosing treatments that produce analgesia by normalizing hyperexcitable central neural activity. We have certainly come a long way since the first discovery of activity-dependent synaptic plasticity in the spinal cord and the revelation that it occurs and produces pain hypersensitivity in patients. Nevertheless, discovering the genetic and environmental contributors to and objective biomarkers of central sensitization will be highly beneficial, as will additional treatment options to prevent or reduce this prevalent and promiscuous form of pain plasticity.", "author" : [ { "dropping-particle" : "", "family" : "Woolf", "given" : "Clifford J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pain", "id" : "ITEM-1", "issue" : "Supplement", "issued" : { "date-parts" : [ [ "2011", "3" ] ] }, "note" : "NULL", "page" : "S2-S15", "title" : "Central sensitization: Implications for the diagnosis and treatment of pain", "type" : "article-journal", "volume" : "152" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(73)", "plainTextFormattedCitation" : "(73)", "previouslyFormattedCitation" : "(73)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(73). In humans, CS manifests as hyperalgesia, allodynia, and spreading of pain and can be reliably assessed in laboratory studies through application of noxious stimuli (see below)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.pain.2010.09.030", "ISSN" : "0304-3959", "PMID" : "20961685", "abstract" : "Nociceptor inputs can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways, the phenomenon of central sensitization. Central sensitization manifests as pain hypersensitivity, particularly dynamic tactile allodynia, secondary punctate or pressure hyperalgesia, aftersensations, and enhanced temporal summation. It can be readily and rapidly elicited in human volunteers by diverse experimental noxious conditioning stimuli to skin, muscles or viscera, and in addition to producing pain hypersensitivity, results in secondary changes in brain activity that can be detected by electrophysiological or imaging techniques. Studies in clinical cohorts reveal changes in pain sensitivity that have been interpreted as revealing an important contribution of central sensitization to the pain phenotype in patients with fibromyalgia, osteoarthritis, musculoskeletal disorders with generalized pain hypersensitivity, headache, temporomandibular joint disorders, dental pain, neuropathic pain, visceral pain hypersensitivity disorders and post-surgical pain. The comorbidity of those pain hypersensitivity syndromes that present in the absence of inflammation or a neural lesion, their similar pattern of clinical presentation and response to centrally acting analgesics, may reflect a commonality of central sensitization to their pathophysiology. An important question that still needs to be determined is whether there are individuals with a higher inherited propensity for developing central sensitization than others, and if so, whether this conveys an increased risk in both developing conditions with pain hypersensitivity, and their chronification. Diagnostic criteria to establish the presence of central sensitization in patients will greatly assist the phenotyping of patients for choosing treatments that produce analgesia by normalizing hyperexcitable central neural activity. We have certainly come a long way since the first discovery of activity-dependent synaptic plasticity in the spinal cord and the revelation that it occurs and produces pain hypersensitivity in patients. Nevertheless, discovering the genetic and environmental contributors to and objective biomarkers of central sensitization will be highly beneficial, as will additional treatment options to prevent or reduce this prevalent and promiscuous form of pain plasticity.", "author" : [ { "dropping-particle" : "", "family" : "Woolf", "given" : "Clifford J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pain", "id" : "ITEM-1", "issue" : "Supplement", "issued" : { "date-parts" : [ [ "2011", "3" ] ] }, "note" : "NULL", "page" : "S2-S15", "title" : "Central sensitization: Implications for the diagnosis and treatment of pain", "type" : "article-journal", "volume" : "152" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(73)", "plainTextFormattedCitation" : "(73)", "previouslyFormattedCitation" : "(73)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(73). A growing literature implicates central sensitization in CP. Repeated and prolonged pain attacks influence the central nervous system and have been shown to alter brain regions in CPADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1053/j.gastro.2007.01.037", "ISSN" : "00165085", "PMID" : "17408654", "abstract" : "BACKGROUND & AIMS In various chronic pain conditions cortical reorganization seems to play a role in the manifestations. The aim of this study was to investigate cortical reorganization in patients with pain caused by chronic pancreatitis. METHODS Twelve healthy subjects and 10 patients with chronic pancreatitis were included. The esophagus, stomach, and duodenum were stimulated electrically at the pain threshold using a nasal endoscope. The electroencephalogram was recorded from 64 surface electrodes and event-related brain potentials (EPs) were obtained. RESULTS As compared with healthy subjects, the patient group showed decreased latencies of the early EP components (N1, P < .001; P1, P = .02), which is thought to reflect the exogenous brain pain processing specifically. Source analysis showed that the dipolar activities corresponding to the early EPs were located consistently in the bilateral insula, in the anterior cingulate gyrus, and in the bilateral secondary somatosensory area. The bilateral insular dipoles were localized more medial in the patient group than in the healthy subjects after stimulation of all 3 gut segments (P < .01). There also were changes in the cingulate cortex where the neuronal source was more posterior in patients than in controls to stimulation of the esophagus (P < .05). CONCLUSIONS The findings indicate that pain in chronic pancreatitis leads to changes in cortical projections of the nociceptive system. Such findings also have been described in somatic pain disorders, among them neuropathic pain. Taken together with the clinical data this suggests a neuropathic component in pancreatic pain, which may influence the approach to treatment.", "author" : [ { "dropping-particle" : "", "family" : "Dimcevski", "given" : "Georg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sami", "given" : "Saber A.K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Funch\u2013Jensen", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pera", "given" : "Domenica", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valeriani", "given" : "Massimiliano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arendt\u2013Nielsen", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2007", "4" ] ] }, "page" : "1546-1556", "title" : "Pain in Chronic Pancreatitis: The Role of Reorganization in the Central Nervous System", "type" : "article-journal", "volume" : "132" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(36)", "plainTextFormattedCitation" : "(36)", "previouslyFormattedCitation" : "(36)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(36). This may be one reason that abdominal imaging or other physiological findings do not correspond with the reported level of painADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.cgh.2014.10.015", "ISSN" : "1542-7714", "PMID" : "25424572", "abstract" : "BACKGROUND & AIMS Chronic pancreatitis is characterized by inflammation, atrophy, fibrosis with progressive ductal changes, and functional changes that include variable exocrine and endocrine insufficiency and multiple patterns of pain. We investigated whether abdominal imaging features accurately predict patterns of pain. METHODS We collected data from participants in the North American Pancreatitis Study 2 Continuation and Validation, a prospective multicenter study of patients with chronic pancreatitis performed at 13 expert centers in the United States from July 2008 through March 2012. Chronic pancreatitis was defined based on the detection of characteristic changes by cross-sectional abdominal imaging, endoscopic retrograde cholangiopancreatography, endoscopic ultrasonography, or histology analyses. Patients were asked by a physician or trained clinical research coordinator if they had any abdominal pain during the year before enrollment, those who responded \"yes\" were asked to select from a list of 5 pain patterns. By using these patterns, we\u00a0classified patients' pain based on timing and severity. Abnormal pancreatitis-associated features on abdominal imaging were recorded using standardized case report forms. RESULTS Data were collected from 518 patients (mean age, 52 \u00b1 14.6 y; 55% male; and 87.6% white). The most common physician-identified etiologies were alcohol (45.8%) and idiopathic (24.3%); 15.6% of patients reported no abdominal pain in the year before enrollment. The most common individual pain pattern was described as constant mild pain with episodes of severe pain and was reported in 45% of patients. The most common imaging findings included pancreatic ductal dilatation (68%), atrophy (57%), and calcifications (55%). Imaging findings were categorized as obstructive for 20% and as inflammatory for 25% of cases. The distribution of individual imaging findings was similar among patients with different patterns of pain. The distribution of pain patterns did not differ among clinically relevant groups of imaging findings. CONCLUSIONS Mechanisms that determine patterns and severity of pain in patients with chronic pancreatitis are largely independent of structural variants observed by abdominal imaging techniques. Pancreas-relevant quantitative and qualitative pain measures should be included in the evaluation of patients with chronic pancreatitis to assess pain severity independently of imaging findings.", "author" : [ { "dropping-particle" : "", "family" : "Wilcox", "given" : "C Mel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yadav", "given" : "Dhiraj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ye", "given" : "Tian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gardner", "given" : "Timothy B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gelrud", "given" : "Andres", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandhu", "given" : "Bimaljit S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lewis", "given" : "Michele D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Al-Kaade", "given" : "Samer", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cote", "given" : "Gregory A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forsmark", "given" : "Christopher E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guda", "given" : "Nalini M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Conwell", "given" : "Darwin L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banks", "given" : "Peter A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muniraj", "given" : "Thiruvengadam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Romagnuolo", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brand", "given" : "Randall E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slivka", "given" : "Adam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sherman", "given" : "Stuart", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wisniewski", "given" : "Stephen R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Whitcomb", "given" : "David C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anderson", "given" : "Michelle A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2015", "3" ] ] }, "note" : "NULL", "page" : "552-60; quiz e28-9", "title" : "Chronic pancreatitis pain pattern and severity are independent of abdominal imaging findings.", "type" : "article-journal", "volume" : "13" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(6)", "plainTextFormattedCitation" : "(6)", "previouslyFormattedCitation" : "(6)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(6). It may also factor in to why pain persists in approximately 30% of patients even after total pancreatectomyADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1159/000108958", "ISSN" : "14243903", "PMID" : "17898531", "abstract" : "Pain in chronic pancreatitis is frequently refractory to medical and even surgical treatment. This refractoriness leads us to believe that a pancreas-independent, brain-mediated mechanism must be responsible. If so, several scenarios are worth considering. First, chronic pain could be the consequence of undesirable neuroplastic changes, by which pathology becomes established and causes disability. Alternatively, pain may be linked to the salutogenic (from salutogenesis, the Latin word for health and well-being) central nervous system response (we defined 'salutogenic response' as the specific modulation of the immune system induced by brain activity changes) to promote healing of the injured viscera. If so, chronic pain could index the ongoing nervous system attempt to promote healing. In this review, we discuss (1) the mechanisms of pain in chronic pancreatitis; (2) potential brain-related salutogenic mechanisms, and (3) the potential relationship of these two factors to the disease status. Furthermore, we consider these aspects in light of a new approach to treat visceral pain: transcranial magnetic stimulation, a noninvasive method of brain stimulation.", "author" : [ { "dropping-particle" : "", "family" : "Fregni", "given" : "Felipe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pascual-Leone", "given" : "Alvaro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freedman", "given" : "Steven D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreatology", "id" : "ITEM-1", "issue" : "5-6", "issued" : { "date-parts" : [ [ "2007", "10" ] ] }, "note" : "NULL", "page" : "411-422", "title" : "Pain in Chronic Pancreatitis: A Salutogenic Mechanism or a Maladaptive Brain Response?", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0002-9610", "PMID" : "8554129", "abstract" : "PURPOSE To examine whether preoperative computed tomography (CT) scans and pancreatograms can: (1) identify patients with chronic pancreatitis localized to the tail of the pancreas; and (2) select those patients who can obtain pain relief from a distal pancreatectomy. PATIENTS AND METHODS Twenty patients were identified on whom the authors had performed distal pancreatectomy for relief of pain between January 1, 1991 and August 1, 1994. The results of surgery were classified as good, fair, or poor based on return to work and need for narcotics or rehospitalization. RESULTS Eleven patients had good, 3 fair, and 6 poor results. All 7 patients with pseudocysts of the tail of the pancreas had good results, while 9 of 13 patients without pseudocysts had poor results. No other finding on CT scan, pancreatography, or laparotomy predicted successful pain relief by distal pancreatectomy. Furthermore, 3 patients had unexpected carcinoma found at the time of surgery. CONCLUSIONS Even when anatomic evidence suggests that chronic pancreatitis primarily involves the tail of the pancreas and there is a stricture of the midpancreatic duct that is believed to cause the symptoms, distal pancreatectomy seldom provides sustained pain relief. Unsuspected carcinoma of the body and tail of the pancreas occurs frequently in this subset of patients with chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Rattner", "given" : "D W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fernandez-del Castillo", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Warshaw", "given" : "A L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American journal of surgery", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "1996", "1" ] ] }, "note" : "NULL", "page" : "142-5; discussion 145-6", "title" : "Pitfalls of distal pancreatectomy for relief of pain in chronic pancreatitis.", "type" : "article-journal", "volume" : "171" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(75,76)", "plainTextFormattedCitation" : "(75,76)", "previouslyFormattedCitation" : "(75,76)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(75,76). Types of assessmentSubjective verbal reports of either a single- or multi-dimensional scale are most common for pain assessment. However, additional methods for evaluating pain, and pain sensitivity are being increasingly employed in CP patients. While single-dimensional verbal reports of pain severity are the norm in the literature, a number of questionnaires have been developed for a more comprehensive pain assessment. For example, the WILDA (words to describe pain, intensity, location, duration, aggravating/alleviating factors)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0899-8280", "PMID" : "16389388", "abstract" : "Pain assessment is critical to optimal pain management interventions. While pain is a highly subjective experience, its management necessitates objective standards of care. The WILDA approach to pain assessment-focusing on words to describe pain, intensity, location, duration, and aggravating or alleviating factors-offers a concise template for assessment in patients with acute and chronic pain.", "author" : [ { "dropping-particle" : "", "family" : "Fink", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Proceedings (Baylor University. Medical Center)", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2000", "7" ] ] }, "note" : "NULL", "page" : "236-9", "title" : "Pain assessment: the cornerstone to optimal pain management.", "type" : "article-journal", "volume" : "13" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(77)", "plainTextFormattedCitation" : "(77)", "previouslyFormattedCitation" : "(77)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(77) pain assessment tool may be useful to aid in this assessment. A commonly used measure in CP, the Izbicki pain score was developed to capture some of the aforementioned dimensions of pain and provide a surrogate score based on the pain attack frequency, pain intensity score (VAS), analgesic use, and duration of disease-related inability to workADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0885-3177", "PMID" : "7667246", "abstract" : "Studies on chronic pancreatitis have focused predominantly on pain measurement, morbidity, and mortality. In this prospective follow-up study the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ) was reevaluated for patients suffering from chronic pancreatitis. Pain intensity was quantified using a specially designed pain score. Twenty-five patients with chronic pancreatitis underwent duodenum-preserving pancreatic head resection. The QLQ, Spitzer's quality of life index, and the pain score were assessed twice before surgery, before discharge, and 6 and 18 months after surgery. The interscale reliability (Cronbach's coefficient alpha > or = 0.70) was confirmed for all multiitem scales except preoperative working ability. Test-retest stability for the QLQ was 94%. The QLQ correlated closely with Spitzer's quality of life index (r = 0.985, p < 0.001) and changes in body weight (r = 0.764, p < 0.001). After 18 months physical status, working ability, emotional and social functioning, and global quality of life had improved by 44, 50, 50, 60, and 67%, respectively, showing good responsiveness of the QLQ. The pain score decreased by 95% (p < 0.001). The EORTC quality of life questionnaire represents a reliable and valid measure of quality of life in patients with chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Bloechle", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Izbicki", "given" : "J R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Knoefel", "given" : "W T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuechler", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Broelsch", "given" : "C E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreas", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "1995", "7" ] ] }, "note" : "NULL", "page" : "77-85", "title" : "Quality of life in chronic pancreatitis--results after duodenum-preserving resection of the head of the pancreas.", "type" : "article-journal", "volume" : "11" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(78)", "plainTextFormattedCitation" : "(78)", "previouslyFormattedCitation" : "(78)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(78). It has, however, never been strictly validated in patients with CP. Future work should consider truly validating this measure in a large sample, particularly since it has become the default pain assessment measure in CP.Subjective Verbal Reports One-dimensional scales (usually pain intensity)One-dimension scales assess a single element of pain, but provide allow for a simple and fast method for patients to self-report the subjectively experienced intensity of their pain. Use of such scales is appropriate in settings of acute pain when the etiology is clear; however, they can oversimplify the pain experienceADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.ajem.2010.12.015", "ISSN" : "07356757", "PMID" : "21367555", "abstract" : "INTRODUCTION Pain is a common presenting complaint among emergency department (ED) patients. The verbal numeric pain scale is commonly used in the ED to assess self-reported pain. This study was undertaken to describe and compare pain scores in a variety of painful conditions and identify factors associated with self-reported pain scores. METHODS The study was a prospective, observational, descriptive survey study conducted at an urban university hospital ED. Eligible participants included consenting adults 18 years and older, with an acute painful condition, who spoke English, and were not in severe distress. Through a structured interview, collected data included pain score; diagnosis; medical history; previous painful experiences; and demographic information including age, insurance status, and highest level of education completed. RESULTS Among 268 eligible participants, 263 (98%) consented and completed the study protocol. Seventy-one percent of participants were 50 years old or younger; 55%, women; and 68%, white. Fifty-four percent had private insurance, and 81%, high school education or higher. The most common chief complaints were soft tissue injury (33%), abdominal pain (18%), and chest pain (13%). The median self-reported pain score was 7/10 (mean, 6.7; interquartile range, 6-9; range, 0-10). The most common previous painful experiences were childbirth (21%), major trauma (18%), and surgery (14%). Participants cited reasons for self-reported pain scores, including current feeling of pain (62%), comparison to previous pain (31%), and comparison to hypothetical pain (12%). The number of previous ED visits was positively correlated with current pain score (Spearman correlation R = 0.28; P < .001). The chief complaints associated with the highest pain scores included dental pain (mean pain score, 8.5) and back pain (mean pain score, 7.6). Chief complaints associated with the lowest pain scores included chest pain (mean pain score, 5.2) and other medical conditions (mean pain score, 5.3). Factors associated with higher pain scores included younger age (P < .001, Kruskal-Wallis), Medicaid insurance (P = .02), and lower educational status (P = .01). There was not a statistically significant association between current pain score and sex, race, previous painful experiences, or number of hospital admissions. CONCLUSION Emergency department patients with acute painful conditions report a wide range of self-reported pain scores. Participants rated pain \u2026", "author" : [ { "dropping-particle" : "", "family" : "Marco", "given" : "Catherine A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nagel", "given" : "Jacqueline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klink", "given" : "Ellen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baehren", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American Journal of Emergency Medicine", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2012", "2" ] ] }, "note" : "NULL", "page" : "331-337", "title" : "Factors associated with self-reported pain scores among ED patients", "type" : "article-journal", "volume" : "30" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(79)", "plainTextFormattedCitation" : "(79)", "previouslyFormattedCitation" : "(79)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(79).These scales use numeric (often 0-10), verbal (eg, mild, severe or other verbal descriptors like discomforting, excruciating…) or visual (pictures of faces, most typically used with children or the cognitively impaired) descriptors to quantify pain or the degree of pain relief. Numerical scales, such as the visual analogue scale (VAS), are commonly applied to assess the intensity of pain in CP patients, but should be combined with a standardized registration of the pain pattern in time including the frequency of pain exacerbationsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/gut.2010.213835", "ISSN" : "1468-3288", "PMID" : "21148579", "abstract" : "OBJECTIVE To compare patients with chronic pancreatitis (CP) with constant pain patterns to patients with CP with intermittent pain patterns. METHODS This was a prospective cohort study conducted at 20 tertiary medical centers in the USA comprising 540 subjects with CP. Patients with CP were asked to identify their pain from five pain patterns (A-E) defined by the temporal nature (intermittent or constant) and the severity of the pain (mild, moderate or severe). Pain pattern types were compared with respect to a variety of demographic, quality of life (QOL) and clinical parameters. Rates of disability were the primary outcome. Secondary outcomes included: use of pain medications, days lost from school or work, hospitalisations (preceding year and lifetime) and QOL as measured using the Short Form-12 (SF-12) questionnaire. RESULTS Of the 540 CP patients, 414 patients (77%) self-identified with a particular pain pattern and were analysed. Patients with constant pain, regardless of severity, had higher rates of disability, hospitalisation and pain medication use than patients with intermittent pain. Patients with constant pain had lower QOL (by SF-12) compared with patients who had intermittent pain. Additionally, patients with constant pain were more likely to have alcohol as the aetiology for their pancreatitis. There was no association between the duration of the disease and the quality or severity of the pain. CONCLUSIONS This is the largest study ever conducted of pain in CP. These findings suggest that the temporal nature of pain is a more important determinant of health-related QOL and healthcare utilisation than pain severity. In contrast to previous studies, the pain associated with CP was not found to change in quality over time. These results have important implications for improving our understanding of the mechanisms underlying pain in CP and for the goals of future treatments and interventions.", "author" : [ { "dropping-particle" : "", "family" : "Mullady", "given" : "Daniel K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yadav", "given" : "Dhiraj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Amann", "given" : "Stephen T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Connell", "given" : "Michael R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barmada", "given" : "Michael M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elta", "given" : "Grace H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scheiman", "given" : "James M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wamsteker", "given" : "Erik-Jan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chey", "given" : "William D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Korneffel", "given" : "Meredith L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weinman", "given" : "Beth M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slivka", "given" : "Adam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sherman", "given" : "Stuart", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hawes", "given" : "Robert H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brand", "given" : "Randall E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burton", "given" : "Frank R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lewis", "given" : "Michele D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gardner", "given" : "Timothy B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gelrud", "given" : "Andres", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "DiSario", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baillie", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banks", "given" : "Peter A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Whitcomb", "given" : "David C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anderson", "given" : "Michelle A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "NAPS2 Consortium", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gut", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2011", "1", "1" ] ] }, "page" : "77-84", "title" : "Type of pain, pain-associated complications, quality of life, disability and resource utilisation in chronic pancreatitis: a prospective cohort study.", "type" : "article-journal", "volume" : "60" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(7)", "plainTextFormattedCitation" : "(7)", "previouslyFormattedCitation" : "(7)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(7).Multidimensional scales Multidimensional scales measure several of the above overviewed aspects of pain, including its intensity, nature and location, and in some cases, pain’s impact on mood or activity level/physical functioning. Evaluating these variables is integral in overall pain assessment and management. Multidimensional scales are valuable in complex or persistent acute or chronic pain cases when intensity needs to be assessed as well as other factors such as quality of life, social support, interference with activities of daily living, and mood. The Brief Pain Inventory (BPI) is one such scale that is commonly used with chronic pain patients and relatively quick. It quantifies pain intensity as well as mood, ability to work, relationships, sleep, enjoyment of life, and the effect of pain on general activity. The BPI also has the ability to evaluate the progress of a patient with a progressive disease and provides an opportunity to evaluate improvement or decline in the assessed domains. BPI scores were recently correlated with quality of life in CP patients, not surprisingly suggesting that the more severe one’s pain, the worse their quality of lifeADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.pan.2014.09.009", "ISSN" : "1424-3911", "PMID" : "25455540", "abstract" : "BACKGROUND/OBJECTIVES Chronic pancreatitis (CP) is a disabling disease characterised by abdominal pain, and various pancreatic and extra-pancreatic complications. We investigated the interactions between pain characteristics (i.e. pain severity and its pattern in time), complications, and quality of life (QOL) in patients with CP. METHODS This was a cross-sectional study of 106 patients with CP conducted at two North European tertiary medical centres. Detailed information on clinical patient characteristics was obtained from interviews and through review of the individual patient records. Pain severity scores and pain pattern time profiles were extracted from the modified brief pain inventory short form and correlated to QOL as assessed by the EORTC QLQ-C30 questionnaire. Interactions with exocrine and endocrine pancreatic insufficiency, as well as pancreatic and extra-pancreatic complications were analysed using regression models. RESULTS Pain was the most prominent symptom in our cohort and its severity was significantly correlated with EORTC global health status (r = -0.46; P < 0.001) and most functional and symptom subscales. In contrast the patterns of pain in time were not associated with any of the life quality subscales. When controlling for interactions from exocrine and endocrine pancreatic insufficiency no effect modifications were evident (P = 0.72 and P = 0.85 respectively), while the presence of pancreatic and extra-pancreatic complications was associated with an almost 15% decrease in life quality (P = 0.004). CONCLUSIONS Pain severity and disease related complications significantly reduce life quality in patients with CP. This information is important in order to design more accurate and clinical meaningful endpoints in future outcome trials.", "author" : [ { "dropping-particle" : "", "family" : "Olesen", "given" : "S\u00f8ren Schou", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Juel", "given" : "Jacob", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nielsen", "given" : "Anders Klitgaard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fr\u00f8kj\u00e6r", "given" : "Jens Br\u00f8ndum", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "Oliver H G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn Mohr", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2014", "11" ] ] }, "note" : "NULL", "page" : "497-502", "title" : "Pain severity reduces life quality in chronic pancreatitis: Implications for design of future outcome trials.", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(13)", "plainTextFormattedCitation" : "(13)", "previouslyFormattedCitation" : "(13)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(13).The McGill Pain Questionnaire is another commonly used survey that assesses three aspects of the pain experience, including sensory, affective, and evaluative dimensions. These components are subdivided into subclasses that represent varying degrees of pain. Seicean and colleaugesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1221-4167", "PMID" : "15054520", "abstract" : "AIM To assess two scores of pain used in chronic pancreatitis, to analyse the morphological factors identified by imaging techniques and the extrinsic factors involved in causing pain and in pain evolution during treatment. PATIENTS AND METHODS Pain was assessed by means of a unidimensional numeric scale and a multidimensional Mc Gill score in 50 patients with chronic pancreatitis. We prospectively followed up 28 patients over a period of 17 months. RESULTS Pain assessment by means of the two scores was statistically comparable. The multidimensional score correlated with the presence of Wirsung stenoses in the univariate analysis and with Wirsung stenoses and their diameter in the multivariate one. The smokers had a smaller rate of pain relief during the treatment. In cases with more morphological changes of severe chronic pancreatitis, pain relief was lower than in cases with fewer changes. CONCLUSIONS The McGill score is more appropriate for the quantitative assessment of pain. Smoking reduces the chances of pain relief under treatment. Duct stenoses and Wirsung diameter have the best correlation with pain intensity. The severe chronic pancreatitis changes are negative predictive factors for pain relief under treatment", "author" : [ { "dropping-particle" : "", "family" : "Seicean", "given" : "Andrada", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grigorescu", "given" : "Mircea", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tan\u0163\u0103u", "given" : "Marcel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dumitra\u015fcu", "given" : "Dan L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pop", "given" : "Diana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mocan", "given" : "Teodora", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Romanian journal of gastroenterology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2004", "3" ] ] }, "note" : "From Duplicate 1 (Pain in chronic pancreatitis: assessment and relief through treatment. - Seicean, Andrada; Grigorescu, Mircea; Tan\u0163\u0103u, Marcel; Dumitra\u015fcu, Dan L; Pop, Diana; Mocan, Teodora)\n\nNULL", "page" : "9-15", "title" : "Pain in chronic pancreatitis: assessment and relief through treatment.", "type" : "article-journal", "volume" : "13" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(80)", "plainTextFormattedCitation" : "(80)", "previouslyFormattedCitation" : "(80)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(80) note that the McGill is a more appropriate pain assessment measure that unidimensional numeric scales alone in CP patients. Quantitative Sensory Testing (QST)Despite tremendous individual differences in clinical outcomes among patients with pancreatitis and the experience of almost daily pain (in approximately 55% of patientsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nrgastro.2011.274", "ISBN" : "1759-5053 (Electronic) 1759-5045 (Linking)", "ISSN" : "1759-5053", "PMID" : "22269952", "abstract" : "Chronic pancreatitis is typically a painful condition and it can be associated with a severe burden of disease. The pathogenesis of pain in this disorder is poorly understood and its treatment has been largely empirical, often consisting of surgical or other invasive methods, with an outcome that is variable and frequently unsatisfactory. Human and experimental studies have indicated a critical role for neuronal mechanisms that result in peripheral and central sensitization. The pancreatic nociceptor seems to be significantly affected in this condition, with increased excitability associated with downregulation of potassium currents. Some of the specific molecules implicated in this process include the vanilloid receptor, TRPV1, nerve growth factor, the protease activated receptor 2 and a variety of others that are discussed in this Review. Studies have also indicated novel therapeutic targets for this condition.", "author" : [ { "dropping-particle" : "", "family" : "Pasricha", "given" : "Pankaj Jay", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jay", "given" : "Pankaj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature reviews. Gastroenterology & hepatology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2012", "1", "24" ] ] }, "page" : "140-51", "publisher" : "Nature Publishing Group", "title" : "Unraveling the mystery of pain in chronic pancreatitis.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(24)", "plainTextFormattedCitation" : "(24)", "previouslyFormattedCitation" : "(24)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(24)), very little is currently known about pain phenotypes in pancreatitis and how these phenotypes predict clinical outcomes. Pain sensitivity and CS can be reliably assessed and quantified in the laboratory using quantitative sensory testing (QST)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.pain.2010.09.030", "ISSN" : "0304-3959", "PMID" : "20961685", "abstract" : "Nociceptor inputs can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways, the phenomenon of central sensitization. Central sensitization manifests as pain hypersensitivity, particularly dynamic tactile allodynia, secondary punctate or pressure hyperalgesia, aftersensations, and enhanced temporal summation. It can be readily and rapidly elicited in human volunteers by diverse experimental noxious conditioning stimuli to skin, muscles or viscera, and in addition to producing pain hypersensitivity, results in secondary changes in brain activity that can be detected by electrophysiological or imaging techniques. Studies in clinical cohorts reveal changes in pain sensitivity that have been interpreted as revealing an important contribution of central sensitization to the pain phenotype in patients with fibromyalgia, osteoarthritis, musculoskeletal disorders with generalized pain hypersensitivity, headache, temporomandibular joint disorders, dental pain, neuropathic pain, visceral pain hypersensitivity disorders and post-surgical pain. The comorbidity of those pain hypersensitivity syndromes that present in the absence of inflammation or a neural lesion, their similar pattern of clinical presentation and response to centrally acting analgesics, may reflect a commonality of central sensitization to their pathophysiology. An important question that still needs to be determined is whether there are individuals with a higher inherited propensity for developing central sensitization than others, and if so, whether this conveys an increased risk in both developing conditions with pain hypersensitivity, and their chronification. Diagnostic criteria to establish the presence of central sensitization in patients will greatly assist the phenotyping of patients for choosing treatments that produce analgesia by normalizing hyperexcitable central neural activity. We have certainly come a long way since the first discovery of activity-dependent synaptic plasticity in the spinal cord and the revelation that it occurs and produces pain hypersensitivity in patients. Nevertheless, discovering the genetic and environmental contributors to and objective biomarkers of central sensitization will be highly beneficial, as will additional treatment options to prevent or reduce this prevalent and promiscuous form of pain plasticity.", "author" : [ { "dropping-particle" : "", "family" : "Woolf", "given" : "Clifford J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pain", "id" : "ITEM-1", "issue" : "Supplement", "issued" : { "date-parts" : [ [ "2011", "3" ] ] }, "note" : "NULL", "page" : "S2-S15", "title" : "Central sensitization: Implications for the diagnosis and treatment of pain", "type" : "article-journal", "volume" : "152" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(73)", "plainTextFormattedCitation" : "(73)", "previouslyFormattedCitation" : "(73)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(73). These calibrated and standardized methods for delivering noxious stimuli under controlled conditionsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0001-5172", "PMID" : "10522737", "abstract" : "Increasing evidence from laboratory methods in humans and animals indicates that pain arises from, and is modulated by, a number of mechanisms. In addition, these mechanisms are not static but change as pain persists. Recent human studies have demonstrated new aspects of pain processing at all levels of the central nervous system. Studies of the influence of analgesic agents on a large number of experimental pain measures have shown a preferential effect of opioids for attenuating the central integration of prolonged stimuli while local anesthetics may be more effective for brief stimulation. Studies of NK1 antagonists in man have shown results similar to those found with animals. There is little effect on brief stimulation of A delta and C-fiber nociceptors, including conditions that can evoke central summation. However, these antagonists, which block the effects of substance P, are effective in more persistent states such as postsurgical pain. Persistent pain can also alter the function of the large diameter A beta touch afferents, ranging from increased tactile sensitivity in inflammatory conditions to frank allodynia following nerve injury or focal nociceptor stimulation. Recent advances in evaluation of supraspinal pain processing in humans have demonstrated pain-related activation using both methods that assess synchronized neural activity and methods that infer this activity in the whole brain by local changes in regional cerebral blood flow. These methods have begun to identify brain regions associated with the multiple dimensions and processing of painful stimulation and the modulation of these processes by pharmacological agents and non-pharmacological interventions.", "author" : [ { "dropping-particle" : "", "family" : "Gracely", "given" : "R H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Acta anaesthesiologica Scandinavica", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "1999", "10" ] ] }, "note" : "NULL", "page" : "897-908", "title" : "Pain measurement.", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(81)", "plainTextFormattedCitation" : "(81)", "previouslyFormattedCitation" : "(81)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(81) are reflective of clinical conditions, as subjects who rate QST stimuli as most painfulADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0033-3174", "PMID" : "10367615", "abstract" : "OBJECTIVE Although numerous studies have reported ethnic differences in the prevalence and severity of clinical pain, little is known about how these differences affect the perception of experimental pain. The present experiment examined the effects of ethnicity (African American vs. white) on thermal pain responses in a healthy undergraduate population. METHODS Thirty white subjects (16 women and 14 men) and 18 African Americans (10 women and 8 men) participated in the study. Thermal testing included evaluation of the following: warmth thresholds, thermal pain thresholds, thermal pain tolerances, and magnitude estimates of both the intensity and unpleasantness of thermal pain (at 46 degrees, 47 degrees, 48 degrees, and 49 degrees C). RESULTS Although no group differences emerged for warmth thresholds, thermal pain thresholds, or pain intensity ratings, African Americans demonstrated lower thermal pain tolerances than whites. In addition, African Americans had smaller slopes and larger intercepts than whites for ratings of pain unpleasantness. Additional analyses suggested that these findings were a consequence of group differences in thermal pain unpleasantness ratings at the lowest temperatures assessed (46 degrees and 47 degrees C); at these temperatures, African Americans rated the stimuli as more unpleasant than whites. Finally, group differences in thermal pain tolerance and thermal pain unpleasantness ratings seemed to partially account for greater self-reported daily pain symptoms among African Americans. CONCLUSIONS Collectively, these findings seem to suggest ethnic differences in the perception of the affective-motivational dimension of thermal pain.", "author" : [ { "dropping-particle" : "", "family" : "Edwards", "given" : "R R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fillingim", "given" : "R B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychosomatic medicine", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "0" ] ] }, "note" : "NULL", "page" : "346-54", "title" : "Ethnic differences in thermal pain responses.", "type" : "article-journal", "volume" : "61" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0304-3959", "PMID" : "10568849", "abstract" : "Considerable research indicates increased experience of clinical pain among females relative to males, and females also demonstrate enhanced responses to experimentally-induced pain. However, previous research has not investigated the relationship between clinical and experimental pain responses in healthy females and males. This experiment examined recent clinical pain as well as thermal pain thresholds and tolerances in 209 (117 female, 92 male) healthy young adults. All subjects completed questionnaires concerning pain-related symptoms over the previous month and subsequently underwent thermal pain assessment. Females reported a larger number of pain sites and greater health care utilization over the month preceding the experimental session, and females also exhibited greater sensitivity to thermal stimuli. In addition, females above the median on the number of pain episodes demonstrated greater thermal pain sensitivity compared to females below the median, but thermal pain responses did not differ as a function of clinical pain among males. The differences remained significant after correcting for psychological variables including hypervigilance and sex role expectancies. These results indicate that experimental pain responses may be more clinically relevant for females than males. Potential explanations and implications for this pattern of results are discussed.", "author" : [ { "dropping-particle" : "", "family" : "Fillingim", "given" : "R B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Edwards", "given" : "R R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Powell", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pain", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "1999", "12" ] ] }, "note" : "NULL", "page" : "419-25", "title" : "The relationship of sex and clinical pain to experimental pain responses.", "type" : "article-journal", "volume" : "83" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(82,83)", "plainTextFormattedCitation" : "(82,83)", "previouslyFormattedCitation" : "(82,83)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(82,83), or show heightened CSADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1054/jpai.2001.25525", "ISSN" : "1526-5900", "PMID" : "14622810", "abstract" : "Although the effects of aging on the experience of clinical pain seem relatively clear, investigations of age-related changes in pain perception using laboratory-based pain assessment procedures have yielded contradictory findings. One potential source of variability in this literature is the type of experimental noxious stimulus that is used. Although thermal pain thresholds are the most commonly reported measure of pain sensitivity, use of suprathreshold stimuli in pain assessment procedures may yield additional, more clinically relevant information concerning the effects of aging on the experience of pain. The present study examined the effects of age on temporal summation of both the intensity and unpleasantness of thermal pain at multiple stimulus temperatures. Specifically, responses to repetitive thermal stimuli delivered to the volar forearm at 47 degrees C, 50 degrees C, and 53 degrees C were assessed in 34 younger (mean age, 22.4 years) and 34 older (mean age, 62.2 years) healthy volunteers. Results suggested that for the 47 degrees C and 50 degrees C stimulus trains, older adults exhibited higher ratings of the intensity and unpleasantness of thermal pain and enhanced temporal summation of thermal pain relative to younger adults. Moreover, thermal pain sensitivity was inversely related to perceptions of general health and to reports of recent clinical pain among younger, but not older, subjects. Collectively these findings may indicate small, although potentially significant, age-related alterations in the plasticity of the central nervous system or endogenous pain-modulatory capacities.", "author" : [ { "dropping-particle" : "", "family" : "Edwards", "given" : "R R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fillingim", "given" : "R B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The journal of pain : official journal of the American Pain Society", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2001", "12" ] ] }, "note" : "NULL", "page" : "307-17", "title" : "Effects of age on temporal summation and habituation of thermal pain: clinical relevance in healthy older and younger adults.", "type" : "article-journal", "volume" : "2" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0304-3959", "PMID" : "14659526", "abstract" : "Laboratory pain research has been criticized as being irrelevant to the clinical experience of pain. Previous findings have been inconsistent with some studies suggesting that experimental pain responses may be related to the reported presence or severity of chronic pain, while others report no such associations. However, few of these studies assess a variety of laboratory pain responses, and none has assessed relationships between clinical pain and diffuse noxious inhibitory controls (DNIC) in healthy subjects. We administered questionnaire measures of pain, quality of life, and psychological variables to a sample of healthy adults participating in a laboratory study of age differences in pain responses. DNIC was not related to other laboratory pain responses, psychological variables, or physiological variables measured in the present study. Regression models predicting health-related quality of life (e.g. pain, physical functioning) revealed that age, sex, and DNIC responses explained between 10 and 25% of the variance in these dependent measures. Of the laboratory pain variables, only DNIC was the sole consistent predictor of clinical pain and physical health, with greater DNIC responses related to less pain, better physical functioning, and better self-rated health. In addition, age differences in DNIC appeared to partially mediate age differences in physical functioning. These findings highlight the potential clinical relevance of experimental pain procedures and suggest that DNIC may be the laboratory pain response most closely associated with clinical pain and health-related variables.", "author" : [ { "dropping-particle" : "", "family" : "Edwards", "given" : "Robert R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ness", "given" : "Timothy J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weigent", "given" : "Douglas A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fillingim", "given" : "Roger B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pain", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2003", "12" ] ] }, "note" : "NULL", "page" : "427-37", "title" : "Individual differences in diffuse noxious inhibitory controls (DNIC): association with clinical variables.", "type" : "article-journal", "volume" : "106" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(84,85)", "plainTextFormattedCitation" : "(84,85)", "previouslyFormattedCitation" : "(84,85)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(84,85) report the most frequent, disabling clinical pain. QST often assess pain thresholds, which has been shown to be stable over time in CPADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/AAP.0b013e3182632c40", "ISSN" : "1532-8651", "PMID" : "22854397", "abstract" : "BACKGROUND AND OBJECTIVES Quantitative sensory testing (QST) has proven to be an important instrument to characterize mechanisms underlying somatic and neuropathic pain disorders. However, its reliability has not previously been established in patients with visceral pain. We investigated the test-retest reliability of static and dynamic QST in patients with visceral pain due to chronic pancreatitis. METHODS Sixty-two patients (38 men, 53 [11] y) with painful chronic pancreatitis were included. Static QST comprised sensory thresholds for pressure and electrical stimulation performed in the ventral and dorsal T10 dermatomes (sharing spinal innervation with the pancreas, ie, pancreatic viscerotomes) and in 4 heterologous regions (control areas). Dynamic QST comprised conditioned pain modulation. Measurements were obtained from 2 subsequent test sessions separated by 1 week. RESULTS The reliability of static QST was generally high, with the best test-retest performance seen for pressure pain thresholds (intraclass correlation coefficients [ICC], 0.74) and electrical sensation thresholds (ICC, 0.66). In contrast, the reliability of dynamic QST was poor (ICC, 0.01). For static QST measures, the reliability was higher for pain thresholds compared with suprapain thresholds (P < 0.01). No differences between assessments in the pancreatic viscerotomes compared with heterologous regions were seen (P = 0.6). CONCLUSIONS Sensory thresholds in the pancreatic viscerotomes and control areas were reproducible over time. In contrast, dynamic QST measurements reflecting active central modulation of pain processing state (ie, conditioned pain modulation) were not stable over time and showed considerable variability. These factors should be taken into consideration in case QST is used to follow disease mechanisms, drug effects, or effects of pain intervention.", "author" : [ { "dropping-particle" : "", "family" : "Olesen", "given" : "S\u00f8ren S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goor", "given" : "Harry", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bouwense", "given" : "Stefan A W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "Oliver H G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Regional anesthesia and pain medicine", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2012" ] ] }, "note" : "NULL", "page" : "530-6", "title" : "Reliability of static and dynamic quantitative sensory testing in patients with painful chronic pancreatitis.", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(86)", "plainTextFormattedCitation" : "(86)", "previouslyFormattedCitation" : "(86)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(86), although more sophisticated, dynamic psychophysical techniques have the potential to more directly assess CNS pain-modulatory processesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.5041/RMMJ.10131", "ISSN" : "20769172", "PMID" : "24228167", "abstract" : "Experimental pain stimuli can be used to simulate patients' pain experience. We review recent developments in psychophysical pain testing, focusing on the application of the dynamic tests-conditioned pain modulation (CPM) and temporal summation (TS). Typically, patients with clinical pain of various types express either less efficient CPM or enhanced TS, or both. These tests can be used in prediction of incidence of acquiring pain and of its intensity, as well as in assisting the correct choice of analgesic agents for individual patients. This can help to shorten the commonly occurring long and frustrating process of adjusting analgesic agents to the individual patients. We propose that evaluating pain modulation can serve as a step forward in individualizing pain medicine.", "author" : [ { "dropping-particle" : "", "family" : "Granovsky", "given" : "Yelena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yarnitsky", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rambam Maimonides medical journal", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2013", "10", "29" ] ] }, "note" : "NULL", "page" : "e0024", "title" : "Personalized pain medicine: the clinical value of psychophysical assessment of pain modulation profile.", "type" : "article-journal", "volume" : "4" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(87)", "plainTextFormattedCitation" : "(87)", "previouslyFormattedCitation" : "(87)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(87). Since incoming nociceptive input is actively regulated at multiple levels of the neuraxis, from spinal cord to cortexADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0077-8923", "PMID" : "12000018", "abstract" : "The traditional specificity theory of pain perception holds that pain involves a direct transmission system from somatic receptors to the brain. The amount of pain perceived, moreover, is assumed to be directly proportional to the extent of injury. Recent research, however, indicates far more complex mechanisms. Clinical and experimental evidence shows that noxious stimuli may sensitize central neural structures involved in pain perception. Salient clinical examples of these effects include amputees with pains in a phantom limb that are similar or identical to those felt in the limb before it was amputated, and patients after surgery who have benefited from preemptive analgesia which blocks the surgery-induced afferent barrage and/or its central consequences. Experimental evidence of these changes is illustrated by the development of sensitization, wind-up, or expansion of receptive fields of CNS neurons, as well as by the enhancement of flexion reflexes and the persistence of pain or hyperalgesia after inputs from injured tissues are blocked. It is clear from the material presented that the perception of pain does not simply involve a moment-to-moment analysis of afferent noxious input, but rather involves a dynamic process that is influenced by the effects of past experiences. Sensory stimuli act on neural systems that have been modified by past inputs, and the behavioral output is significantly influenced by the \"memory\" of these prior events. An increased understanding of the central changes induced by peripheral injury or noxious stimulation should lead to new and improved clinical treatment for the relief and prevention of pathological pain.", "author" : [ { "dropping-particle" : "", "family" : "Melzack", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Coderre", "given" : "T J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katz", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vaccarino", "given" : "A L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the New York Academy of Sciences", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2001", "3" ] ] }, "note" : "NULL", "page" : "157-74", "title" : "Central neuroplasticity and pathological pain.", "type" : "article-journal", "volume" : "933" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0022-0337", "PMID" : "11780656", "abstract" : "The neuromatrix theory of pain proposes that pain is a multidimensional experience produced by characteristic \"neurosignature\" patterns of nerve impulses generated by a widely distributed neural network-the \"body-self neuromatrix\"-in the brain. These neurosignature patterns may be triggered by sensory inputs, but they may also be generated independently of them. Acute pains evoked by brief noxious inputs have been meticulously investigated by neuroscientists, and their sensory transmission mechanisms are generally well understood. In contrast, chronic pain syndromes, which are often characterized by severe pain associated with little or no discernible injury or pathology, remain a mystery. Furthermore, chronic psychological or physical stress is often associated with chronic pain, but the relationship is poorly understood. The neuromatrix theory of pain provides a new conceptual framework to examine these problems. It proposes that the output patterns of the body-self neuromatrix activate perceptual, homeostatic, and behavioral programs after injury, pathology, or chronic stress. Pain, then, is produced by the output of a widely distributed neural network in the brain rather than directly by sensory input evoked by injury, inflammation, or other pathology. The neuromatrix, which is genetically determined and modified by sensory experience, is the primary mechanism that generates the neural pattern that produces pain. Its output pattern is determined by multiple influences, of which the somatic sensory input is only a part, that converge on the neuromatrix.", "author" : [ { "dropping-particle" : "", "family" : "Melzack", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of dental education", "id" : "ITEM-2", "issue" : "12", "issued" : { "date-parts" : [ [ "2001", "12" ] ] }, "note" : "NULL", "page" : "1378-82", "title" : "Pain and the neuromatrix in the brain.", "type" : "article-journal", "volume" : "65" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(88,89)", "plainTextFormattedCitation" : "(88,89)", "previouslyFormattedCitation" : "(88,89)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(88,89), it is important to understand individual differences in CNS pain-facilitatory and pain-inhibitory processes, which maps on to pain chronification and the variability reported among chronic pain patientsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/SPC.0000000000000055", "ISSN" : "1751-4266", "PMID" : "24752199", "abstract" : "PURPOSE OF REVIEW Chronic pain is an important public health problem that negatively impacts quality of life of affected individuals and exacts an enormous socio-economic cost. Currently available therapeutics provide inadequate management of pain in many patients. Acute pain states generally resolve in most patients. However, for reasons that are poorly understood, in some individuals, acute pain can transform to a chronic state. Our understanding of the risk factors that underlie the development of chronic pain is limited. Recent studies have suggested an important contribution of dysfunction in descending pain modulatory circuits to pain 'chronification'. Human studies provide insights into possible endogenous and exogenous factors that may promote the conversion of pain into a chronic condition. RECENT FINDINGS Descending pain modulatory systems have been studied and characterized in animal models. Human brain imaging techniques, deep brain stimulation and the mechanisms of action of drugs that are effective in the treatment of pain confirm the clinical relevance of top-down pain modulatory circuits. Growing evidence supports the concept that chronic pain is associated with a dysregulation in descending pain modulation. Disruption of the balance of descending modulatory circuits to favour facilitation may promote and maintain chronic pain. Recent findings suggest that diminished descending inhibition is likely to be an important element in determining whether pain may become chronic. This view is consistent with the clinical success of drugs that enhance spinal noradrenergic activity, such as serotonin/norepinephrine reuptake inhibitors (SNRIs), in the treatment of chronic pain states. Consistent with this concept, a robust descending inhibitory system may be normally engaged to protect against the development of chronic pain. Imaging studies show that higher cortical and subcortical centres that govern emotional, motivational and cognitive processes communicate directly with descending pain modulatory circuits providing a mechanistic basis to explain how exogenous factors can influence the expression of chronic pain in a susceptible individual. SUMMARY Preclinical studies coupled with clinical pharmacologic and neuroimaging investigations have advanced our understanding of brain circuits that modulate pain. Descending pain facilitatory and inhibitory circuits arising ultimately in the brainstem provide mechanisms that can be engaged to promote or p\u2026", "author" : [ { "dropping-particle" : "", "family" : "Ossipov", "given" : "Michael H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morimura", "given" : "Kozo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Porreca", "given" : "Frank", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current opinion in supportive and palliative care", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2014", "6" ] ] }, "note" : "NULL", "page" : "143-51", "title" : "Descending pain modulation and chronification of pain.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(90)", "plainTextFormattedCitation" : "(90)", "previouslyFormattedCitation" : "(90)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(90). Participants who rate such calibrated noxious stimuli as most painfulADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0033-3174", "PMID" : "10367615", "abstract" : "OBJECTIVE Although numerous studies have reported ethnic differences in the prevalence and severity of clinical pain, little is known about how these differences affect the perception of experimental pain. The present experiment examined the effects of ethnicity (African American vs. white) on thermal pain responses in a healthy undergraduate population. METHODS Thirty white subjects (16 women and 14 men) and 18 African Americans (10 women and 8 men) participated in the study. Thermal testing included evaluation of the following: warmth thresholds, thermal pain thresholds, thermal pain tolerances, and magnitude estimates of both the intensity and unpleasantness of thermal pain (at 46 degrees, 47 degrees, 48 degrees, and 49 degrees C). RESULTS Although no group differences emerged for warmth thresholds, thermal pain thresholds, or pain intensity ratings, African Americans demonstrated lower thermal pain tolerances than whites. In addition, African Americans had smaller slopes and larger intercepts than whites for ratings of pain unpleasantness. Additional analyses suggested that these findings were a consequence of group differences in thermal pain unpleasantness ratings at the lowest temperatures assessed (46 degrees and 47 degrees C); at these temperatures, African Americans rated the stimuli as more unpleasant than whites. Finally, group differences in thermal pain tolerance and thermal pain unpleasantness ratings seemed to partially account for greater self-reported daily pain symptoms among African Americans. CONCLUSIONS Collectively, these findings seem to suggest ethnic differences in the perception of the affective-motivational dimension of thermal pain.", "author" : [ { "dropping-particle" : "", "family" : "Edwards", "given" : "R R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fillingim", "given" : "R B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychosomatic medicine", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "0" ] ] }, "note" : "NULL", "page" : "346-54", "title" : "Ethnic differences in thermal pain responses.", "type" : "article-journal", "volume" : "61" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0304-3959", "PMID" : "10568849", "abstract" : "Considerable research indicates increased experience of clinical pain among females relative to males, and females also demonstrate enhanced responses to experimentally-induced pain. However, previous research has not investigated the relationship between clinical and experimental pain responses in healthy females and males. This experiment examined recent clinical pain as well as thermal pain thresholds and tolerances in 209 (117 female, 92 male) healthy young adults. All subjects completed questionnaires concerning pain-related symptoms over the previous month and subsequently underwent thermal pain assessment. Females reported a larger number of pain sites and greater health care utilization over the month preceding the experimental session, and females also exhibited greater sensitivity to thermal stimuli. In addition, females above the median on the number of pain episodes demonstrated greater thermal pain sensitivity compared to females below the median, but thermal pain responses did not differ as a function of clinical pain among males. The differences remained significant after correcting for psychological variables including hypervigilance and sex role expectancies. These results indicate that experimental pain responses may be more clinically relevant for females than males. Potential explanations and implications for this pattern of results are discussed.", "author" : [ { "dropping-particle" : "", "family" : "Fillingim", "given" : "R B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Edwards", "given" : "R R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Powell", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pain", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "1999", "12" ] ] }, "note" : "NULL", "page" : "419-25", "title" : "The relationship of sex and clinical pain to experimental pain responses.", "type" : "article-journal", "volume" : "83" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(82,83)", "plainTextFormattedCitation" : "(82,83)", "previouslyFormattedCitation" : "(82,83)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(82,83), who show the greatest CNS sensitizabilityADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1054/jpai.2001.25525", "ISSN" : "1526-5900", "PMID" : "14622810", "abstract" : "Although the effects of aging on the experience of clinical pain seem relatively clear, investigations of age-related changes in pain perception using laboratory-based pain assessment procedures have yielded contradictory findings. One potential source of variability in this literature is the type of experimental noxious stimulus that is used. Although thermal pain thresholds are the most commonly reported measure of pain sensitivity, use of suprathreshold stimuli in pain assessment procedures may yield additional, more clinically relevant information concerning the effects of aging on the experience of pain. The present study examined the effects of age on temporal summation of both the intensity and unpleasantness of thermal pain at multiple stimulus temperatures. Specifically, responses to repetitive thermal stimuli delivered to the volar forearm at 47 degrees C, 50 degrees C, and 53 degrees C were assessed in 34 younger (mean age, 22.4 years) and 34 older (mean age, 62.2 years) healthy volunteers. Results suggested that for the 47 degrees C and 50 degrees C stimulus trains, older adults exhibited higher ratings of the intensity and unpleasantness of thermal pain and enhanced temporal summation of thermal pain relative to younger adults. Moreover, thermal pain sensitivity was inversely related to perceptions of general health and to reports of recent clinical pain among younger, but not older, subjects. Collectively these findings may indicate small, although potentially significant, age-related alterations in the plasticity of the central nervous system or endogenous pain-modulatory capacities.", "author" : [ { "dropping-particle" : "", "family" : "Edwards", "given" : "R R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fillingim", "given" : "R B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The journal of pain : official journal of the American Pain Society", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2001", "12" ] ] }, "note" : "NULL", "page" : "307-17", "title" : "Effects of age on temporal summation and habituation of thermal pain: clinical relevance in healthy older and younger adults.", "type" : "article-journal", "volume" : "2" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(84)", "plainTextFormattedCitation" : "(84)", "previouslyFormattedCitation" : "(84)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(84) and the least endogenous pain inhibitionADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0304-3959", "PMID" : "14659526", "abstract" : "Laboratory pain research has been criticized as being irrelevant to the clinical experience of pain. Previous findings have been inconsistent with some studies suggesting that experimental pain responses may be related to the reported presence or severity of chronic pain, while others report no such associations. However, few of these studies assess a variety of laboratory pain responses, and none has assessed relationships between clinical pain and diffuse noxious inhibitory controls (DNIC) in healthy subjects. We administered questionnaire measures of pain, quality of life, and psychological variables to a sample of healthy adults participating in a laboratory study of age differences in pain responses. DNIC was not related to other laboratory pain responses, psychological variables, or physiological variables measured in the present study. Regression models predicting health-related quality of life (e.g. pain, physical functioning) revealed that age, sex, and DNIC responses explained between 10 and 25% of the variance in these dependent measures. Of the laboratory pain variables, only DNIC was the sole consistent predictor of clinical pain and physical health, with greater DNIC responses related to less pain, better physical functioning, and better self-rated health. In addition, age differences in DNIC appeared to partially mediate age differences in physical functioning. These findings highlight the potential clinical relevance of experimental pain procedures and suggest that DNIC may be the laboratory pain response most closely associated with clinical pain and health-related variables.", "author" : [ { "dropping-particle" : "", "family" : "Edwards", "given" : "Robert R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ness", "given" : "Timothy J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weigent", "given" : "Douglas A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fillingim", "given" : "Roger B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pain", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2003", "12" ] ] }, "note" : "NULL", "page" : "427-37", "title" : "Individual differences in diffuse noxious inhibitory controls (DNIC): association with clinical variables.", "type" : "article-journal", "volume" : "106" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(85)", "plainTextFormattedCitation" : "(85)", "previouslyFormattedCitation" : "(85)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(85), report the most frequent, disabling daily pain complaints (e.g., headaches, backaches, etc.). Such pain-sensitive individuals (i.e., lower pain threshold, higher pain ratings of standardized noxious stimuli) also obtain the least benefits following multidisciplinary treatment for chronic painADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0304-3959", "PMID" : "14659525", "abstract" : "Sex-related differences in the experience of clinical and experimental pain have been widely reported. Females are at elevated risk for developing several chronic pain conditions and women demonstrate greater sensitivity to noxious stimulation in the laboratory. However, relationships between responses to experimental noxious stimuli and the experience of clinical pain have not been well characterized. One previous study of healthy adults indicated that pain threshold and tolerance were associated with clinical pain among women but not men (i.e. females with lower pain threshold and tolerance reported more clinical pain). In the present investigation, relationships between pain tolerance and outcomes of treatment for chronic pain were evaluated in a sex-dependent manner. Ischemic pain tolerance was assessed prior to treatment in 171 chronic pain patients completing a pain management program. Outcomes were measured as changes in pain severity, affect, and pain-related disability. Over the course of treatment, women demonstrated greater improvement in pain-related disability while men showed more reduction in pain. Ischemic pain tolerance was related to outcome in a sex-specific fashion. Women with higher pain tolerances showed greater improvement in pain, more reduction in pain-related interference, and more increases in activity level than women with lower pain tolerances. In contrast, pain tolerance was not associated with positive treatment outcomes among men. These results indicate that experimental pain responses may be most clinically relevant for women, and that sex differences may exist in the determinants of pain-treatment outcomes.", "author" : [ { "dropping-particle" : "", "family" : "Edwards", "given" : "Robert R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doleys", "given" : "Daniel M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lowery", "given" : "Daniel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fillingim", "given" : "Roger B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pain", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2003", "12" ] ] }, "note" : "NULL", "page" : "419-26", "title" : "Pain tolerance as a predictor of outcome following multidisciplinary treatment for chronic pain: differential effects as a function of sex.", "type" : "article-journal", "volume" : "106" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(91)", "plainTextFormattedCitation" : "(91)", "previouslyFormattedCitation" : "(91)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(91), experience enhanced acute postoperative pain in a number of surgical proceduresADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0304-3959", "PMID" : "11207398", "abstract" : "Small-scale studies have suggested a large inter-individual variation in early postoperative pain after laparoscopic cholecystectomy, emphasizing the need for improved analgesic treatment and valid predictors. We investigated prospectively the association between a preoperative nociceptive stimulus by ice water (cold pressor test), neuroticism, dyspepsia, patient history of biliary symptoms, intraoperative factors, and demographic information in 150 consecutive patients undergoing uncomplicated laparoscopic cholecystectomy for their influence on early postoperative pain. During the first postoperative week patients registered overall pain, incisional, visceral, and shoulder pain on a visual analogue scale and verbal rating scale, and daily analgesic requirements were noted. Throughout the first postoperative week overall pain showed a pronounced inter-individual variability. Incisional pain dominated in incidence and intensity compared with visceral pain, which in turn dominated over shoulder pain. In a multivariate analysis model, preoperative neuroticism, sensitivity to cold pressor-induced pain, and age were identified as independent risk factors for early postoperative pain. Our results suggest that future analgesic studies after laparoscopic cholecystectomy should focus on reduction of incisional pain.", "author" : [ { "dropping-particle" : "", "family" : "Bisgaard", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klarskov", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rosenberg", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kehlet", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pain", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2001", "2", "15" ] ] }, "note" : "NULL", "page" : "261-9", "title" : "Characteristics and prediction of early pain after laparoscopic cholecystectomy.", "type" : "article-journal", "volume" : "90" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0003-3022", "PMID" : "14695732", "abstract" : "BACKGROUND Despite major advances in the understanding of the neurobiologic mechanisms of pain, the wide variation in acute pain experience has not been well explained. Therefore, the authors investigated the potential of a preoperatively induced heat injury to predict subsequent postoperative pain ratings in patients undergoing knee surgery. METHODS Twenty patients were studied. The burn injury was induced 6 days before surgery with a contact thermode (12.5 cm2, 47 degrees C for 7 min). The sensory testing, before and 1 h after the injury, included pain score during induction of the burn, secondary hyperalgesia area, thermal and mechanical pain perception, and pain thresholds. Postoperative analgesia consisted of ibuprofen and acetaminophen. Pain ratings (visual analog scale) at rest and during limb movement were followed for 10 days after surgery. RESULTS The burn injury was associated with development of significant hyperalgesia. There was a significant correlation between preoperative pain ratings during the burn injury and early (0-2 days, area under the curve) and late (3-10 days, area under the curve) postoperative dynamic pain ratings during limb movement. CONCLUSION The results of this study suggest that the pain response to a preoperative heat injury may be useful in research in predicting the intensity of postoperative pain. These findings may have important implications to identify patients at risk for development of chronic pain and to stratify individuals for investigations of new analgesics.", "author" : [ { "dropping-particle" : "", "family" : "Werner", "given" : "Mads U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duun", "given" : "Preben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kehlet", "given" : "Henrik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Anesthesiology", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2004", "1" ] ] }, "note" : "NULL", "page" : "115-9; discussion 5A", "title" : "Prediction of postoperative pain by preoperative nociceptive responses to heat stimulation.", "type" : "article-journal", "volume" : "100" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.jpain.2004.03.005", "ISSN" : "1526-5900", "PMID" : "15162345", "abstract" : "UNLABELLED The chronic pain syndrome of vulvar vestibulitis is a major cause of sexual dysfunction, and complete cure is not always achieved. The aim of the study was to determine whether the psychophysical characteristics of systemic pain perception predict treatment choice and outcome. Ninety women with vulvar vestibulitis syndrome were evaluated by using quantitative sensory testing with heat pain threshold measurements and pain scores for suprathreshold stimuli applied to the forearm, blood pressure measurements, and an assessment of the number of other pain disorders. Women were free to choose a surgical procedure (ie, vestibulectomy), one of the possible nonsurgical treatments (eg, biofeedback, cognitive-behavioral therapy, or hypoallergic agents), or to avoid treatment entirely. Eight months later, women reported the success of the treatment on the basis of reduction in the level of vulvar pain. Vestibulectomy demonstrated the best therapeutic effectiveness (chi2, 26.4; P <.0001). Women who chose this type of treatment had lower pain scores (P =.038) and fewer pain syndromes other than the vulvar pain (P =.025). Logistic regression analysis, controlling for the effect of vestibulectomy, indicated that lower experimental pain scores (P =.044), fewer pain disorders (P =.023), and higher systolic blood pressure (P =.039) are predictive variables for reduction of vulvar pain. An assessment of systemic pain perception might be helpful in choosing the optimal treatment and in predicting its success. PERSPECTIVE The present study suggests that pain perception variables might be of value in the prediction of treatment choice and outcome among women with vulvar vestibulitis.", "author" : [ { "dropping-particle" : "", "family" : "Granot", "given" : "Michal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zimmer", "given" : "Etan Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Friedman", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lowenstein", "given" : "Lior", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yarnitsky", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The journal of pain : official journal of the American Pain Society", "id" : "ITEM-3", "issue" : "4", "issued" : { "date-parts" : [ [ "2004", "5" ] ] }, "note" : "NULL", "page" : "226-32", "title" : "Association between quantitative sensory testing, treatment choice, and subsequent pain reduction in vulvar vestibulitis syndrome.", "type" : "article-journal", "volume" : "5" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "ISSN" : "0003-3022", "PMID" : "16129988", "abstract" : "BACKGROUND The goal of this study was to evaluate whether preoperative pressure pain sensitivity testing is predictive of postoperative surgical pain. METHODS Female subjects undergoing lower abdominal gynecologic surgery were studied. A pressure algometer was used preoperatively to determine the pressure pain threshold and tolerance. A visual analog scale (VAS) was used to assess postoperative pain. A State-Trait Anxiety Inventory was used to assess patients' anxiety. Subjects received intravenous patient-controlled analgesia for postoperative pain control. The preoperative pain threshold and tolerance were compared with the postoperative VAS pain score and morphine consumption. RESULTS Forty women were enrolled. Their preoperative pressure pain threshold and tolerance were 141 +/- 65 kPa and 223 +/- 62 kPa, respectively. The VAS pain score in the postanesthesia care unit and at 24 h postoperatively were 81 +/- 24 and 31 +/- 10, respectively. Highly anxious patients had higher VAS pain scores in the postanesthesia care unit (P < 0.05). Pressure pain tolerance was significantly correlated with the VAS at 24 h postoperatively (P < 0.001, r = -0.52). Pressure pain tolerance after fentanyl administration (mean, 272 +/- 68 kPa) correlated significantly with morphine consumption in the first 24 h postoperatively (P < 0.002, r = -0.48). CONCLUSIONS Assessment of preoperative pressure pain tolerance is significantly correlated with the level of postoperative pain. Pain tolerance assessment after fentanyl was administered and fentanyl sensitivity predicted the dose of analgesics used in the first 24 h after surgery. The algometer is thus a simple, useful tool for predicting postoperative pain and analgesic consumption.", "author" : [ { "dropping-particle" : "", "family" : "Hsu", "given" : "Yung-Wei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Somma", "given" : "Jacques", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hung", "given" : "Yu-Chun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsai", "given" : "Pei-Shan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yang", "given" : "Chen-Hsien", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Chien-Chuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Anesthesiology", "id" : "ITEM-4", "issue" : "3", "issued" : { "date-parts" : [ [ "2005", "9" ] ] }, "note" : "NULL", "page" : "613-8", "title" : "Predicting postoperative pain by preoperative pressure pain assessment.", "type" : "article-journal", "volume" : "103" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1016/j.urology.2007.05.012", "ISSN" : "1527-9995", "PMID" : "17991537", "abstract" : "OBJECTIVES To evaluate whether assessment of experimental pain perception using the modified tourniquet test before a biopsy procedure could predict the pain scores during transrectal ultrasound-guided prostate biopsy. However, the relationship between the experimental pain assessment before prostate biopsy and the pain scores during the biopsy procedure has not been established. METHODS A total of 67 men who underwent transrectal ultrasound-guided 12-core prostate biopsy were prospectively enrolled in the study. The day before biopsy, a modified submaximal effort tourniquet test was performed on all patients. During the test, pain scores were recorded at 30, 60, 90, and 120 seconds after inflation of the blood pressure cuff. Pain scores were also recorded during probe introduction into the rectum and prostate biopsy. Pain was assessed using a visual analogue scale (VAS). RESULTS A significant correlation was found between the VAS scores in the tourniquet test and the VAS scores during probe introduction and the VAS scores during prostate biopsy (P <0.0001). The most significant correlation was found between the VAS scores during prostate biopsy and the VAS 60-second scores during the tourniquet test (P <0.0001, r=0.756). No significant relation was found between the VAS scores and age, prostate volume, or prostate-specific antigen level (P >0.05). CONCLUSIONS Our results have shown that a simple and quick tourniquet test could be useful in identifying those men who will experience greater pain during transrectal ultrasound-guided prostate biopsy. In the light of these data, additional studies will be planned to evaluate whether experimental pain assessment before the procedure could predict the analgesic potency of pain-relieving treatment during prostate biopsy.", "author" : [ { "dropping-particle" : "", "family" : "Soyupek", "given" : "Sedat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bozlu", "given" : "Murat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arma\u011fan", "given" : "Abdullah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ozorak", "given" : "Alper", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perk", "given" : "Hakki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Urology", "id" : "ITEM-5", "issue" : "4", "issued" : { "date-parts" : [ [ "2007", "10" ] ] }, "note" : "NULL", "page" : "681-4", "title" : "Does experimental pain assessment before biopsy predict for pain during transrectal ultrasound-guided prostate biopsy?", "type" : "article-journal", "volume" : "70" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "ISSN" : "0003-3022", "PMID" : "12766652", "abstract" : "BACKGROUND Postcesarean section pain is a common cause of acute pain in obstetrics, yet pain relief and patient satisfaction are still inadequate in many cases. The present study was conducted to determine whether preoperative assessment of experimental pain perception by quantitative sensory tests could predict the level of postcesarean section pain. METHODS Fifty-eight women who were scheduled for elective cesarean section were enrolled in the study. Heat pain threshold and magnitude estimation of suprathreshold pain stimuli at 44 degrees-48 degrees C were assessed for both algosity (the sensory dimension of pain intensity) and unpleasantness 1 or 2 days before surgery. The day after the operation, the women reported the level of pain at the surgical wound on a visual analog scale at rest and during activity. Regression analysis was performed to evaluate the usefulness of preoperative scores in predicting postcesarean section pain. RESULTS Postoperative visual analog scale scores at rest and during activity significantly correlated with preoperative suprathreshold pain scores at 44 degrees-48 degrees C (r = 0.31-0.58 for algosity and r = 0.33-0.74 for unpleasantness). The stimulus of 48 degrees C was found to be the best predictor of postoperative pain for both conditions (r = 0.434-0.527; P < 0.01). In contrast to suprathreshold pain stimuli, pain threshold was not correlated with postoperative pain. CONCLUSIONS The results show that a simple and quick preoperative test is useful in identifying those women who will experience greater pain after a cesarean section. This test may be suggested for caregivers to tailor the postoperative treatment to specific patient needs and to improve postoperative outcome and patient satisfaction.", "author" : [ { "dropping-particle" : "", "family" : "Granot", "given" : "Michal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lowenstein", "given" : "Lior", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yarnitsky", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tamir", "given" : "Ada", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zimmer", "given" : "Etan Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Anesthesiology", "id" : "ITEM-6", "issue" : "6", "issued" : { "date-parts" : [ [ "2003", "6" ] ] }, "note" : "NULL", "page" : "1422-6", "title" : "Postcesarean section pain prediction by preoperative experimental pain assessment.", "type" : "article-journal", "volume" : "98" }, "uris" : [ "" ] }, { "id" : "ITEM-7", "itemData" : { "DOI" : "10.1111/j.1399-6576.2007.01271.x", "ISSN" : "0001-5172", "PMID" : "17430320", "abstract" : "BACKGROUND Treatment of post-operative pain is still a significant problem. Recently, interest has focused on pre-operative identification of patients who may experience severe post-operative pain in order to offer a more aggressive analgesic treatment. The nociceptive stimulation methods have included heat injury and pressure algometry. A simple method, Pain Matcher (PM), using electrical stimulation, is validated for pain assessment, but has not been evaluated as a tool for prediction of post-operative pain. Our aim was to assess the predictive value of pre-caesarean section pain threshold on intensity of post-caesarean section pain using the PM. PATIENTS AND METHODS Thirty-nine healthy women scheduled for elective caesarean section were studied. The anaesthetic/analgesic procedures included spinal anaesthesia, paracetamol, diclofenac, controlled-release (CR) oxycodone and morphine on request. Pre-operatively, the sensory and pain thresholds were measured using the PM. Post-operatively, a midwife, blinded for pre-caesarean pain threshold assessments, assessed the pain at rest and during mobilization every 12 h for 2 days. Consumption of analgesics was also recorded. RESULTS Pre-operative pain threshold correlated significantly with post-caesarean pain score (VAS) at rest and mobilization: [Spearman's rho =-0.65 (-0.30 to -0.75), P < 0.01] and [Spearman's rho =-0.52 (-0.23 to -0.72), P < 0.01], respectively. There was no significant correlation between pre-operative PM assessment of sensory threshold and post-operative pain. CONCLUSION Electrical pain threshold before caesarean section seems to predict the intensity of post-operative pain. This method may be used as a screening tool to identify patients at high risk of post-operative pain.", "author" : [ { "dropping-particle" : "", "family" : "Nielsen", "given" : "P R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "N\u00f8rgaard", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rasmussen", "given" : "L S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kehlet", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Acta anaesthesiologica Scandinavica", "id" : "ITEM-7", "issue" : "5", "issued" : { "date-parts" : [ [ "2007", "5" ] ] }, "note" : "NULL", "page" : "582-6", "title" : "Prediction of post-operative pain by an electrical pain stimulus.", "type" : "article-journal", "volume" : "51" }, "uris" : [ "" ] }, { "id" : "ITEM-8", "itemData" : { "DOI" : "10.1016/j.pain.2004.12.007", "ISSN" : "0304-3959", "PMID" : "15733636", "abstract" : "Patients with postoperative ongoing sciatic pain have been shown to exhibit reduced cortisol levels along with enhanced IL-6 levels. The aim of the present study was to clarify the relationship between a reduced cortisol secretion and enhanced cytokine levels by performing a prospective study on patients with disc herniation. Twenty-two patients were examined before and after their disc surgery. Twelve healthy, pain-free subjects matched for age, education and gender constituted the control group. The preoperative examinations included the assessment of the diurnal pattern of cortisol secretion and the feedback sensitivity of the hypothalamus-pituitary-adrenal (HPA) axis. Patients' subjective stress levels also were assessed during the preoperative examination. The diurnal pattern of cortisol secretion was again assessed during the postoperative examination. Furthermore, blood samples were collected to measure catecholamine, adrenocorticotropic hormone (ACTH)- and interleukin-6 (IL-6) levels before and after measuring the pressure pain thresholds (PPTs). An assessment of the sensitivity of circulating monocytes to the immunosuppressive effects of glucocorticoids was further included in the postoperative examinations. Failed back syndrome (FBS) patients (n=12) showed a reduced cortisol secretion in the morning hours and enhanced feedback sensitivity of the HPA axis. Furthermore, FBS patients displayed an increased in-vitro production of proinflammatory cytokines and a relative glucocorticoid resistance of pro-inflammatory cytokine producing monocytes as compared to non-FBS patients (n=10) and controls. After PPT measurement FBS patients exhibited an increased norepinephrine but decreased epinephrine response, together with lower ACTH levels and a four times higher plasma IL-6 response. These findings suggest that chronically stressed patients are at a higher risk for a poor surgical outcome as their reduced cortisol secretion promotes the postoperative ongoing synthesis of proinflammatory cytokines.", "author" : [ { "dropping-particle" : "", "family" : "Geiss", "given" : "Andrea", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rohleder", "given" : "Nicolas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kirschbaum", "given" : "Clemens", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinbach", "given" : "Klaus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bauer", "given" : "Heinz W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anton", "given" : "Fernand", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pain", "id" : "ITEM-8", "issue" : "1-2", "issued" : { "date-parts" : [ [ "2005", "3" ] ] }, "note" : "NULL", "page" : "104-17", "title" : "Predicting the failure of disc surgery by a hypofunctional HPA axis: evidence from a prospective study on patients undergoing disc surgery.", "type" : "article-journal", "volume" : "114" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(92\u201399)", "plainTextFormattedCitation" : "(92\u201399)", "previouslyFormattedCitation" : "(92\u201399)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(92–99), are at risk for developing chronic pain following surgeryADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.pain.2007.10.033", "ISSN" : "1872-6623", "PMID" : "18079062", "abstract" : "Surgical and medical procedures, mainly those associated with nerve injuries, may lead to chronic persistent pain. Currently, one cannot predict which patients undergoing such procedures are 'at risk' to develop chronic pain. We hypothesized that the endogenous analgesia system is key to determining the pattern of handling noxious events, and therefore testing diffuse noxious inhibitory control (DNIC) will predict susceptibility to develop chronic post-thoracotomy pain (CPTP). Pre-operative psychophysical tests, including DNIC assessment (pain reduction during exposure to another noxious stimulus at remote body area), were conducted in 62 patients, who were followed 29.0+/-16.9 weeks after thoracotomy. Logistic regression revealed that pre-operatively assessed DNIC efficiency and acute post-operative pain intensity were two independent predictors for CPTP. Efficient DNIC predicted lower risk of CPTP, with OR 0.52 (0.33-0.77 95% CI, p=0.0024), i.e., a 10-point numerical pain scale (NPS) reduction halves the chance to develop chronic pain. Higher acute pain intensity indicated OR of 1.80 (1.28-2.77, p=0.0024) predicting nearly a double chance to develop chronic pain for each 10-point increase. The other psychophysical measures, pain thresholds and supra-threshold pain magnitudes, did not predict CPTP. For prediction of acute post-operative pain intensity, DNIC efficiency was not found significant. Effectiveness of the endogenous analgesia system obtained at a pain-free state, therefore, seems to reflect the individual's ability to tackle noxious events, identifying patients 'at risk' to develop post-intervention chronic pain. Applying this diagnostic approach before procedures that might generate pain may allow individually tailored pain prevention and management, which may substantially reduce suffering.", "author" : [ { "dropping-particle" : "", "family" : "Yarnitsky", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crispel", "given" : "Yonathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eisenberg", "given" : "Elon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Granovsky", "given" : "Yelena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ben-Nun", "given" : "Alon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sprecher", "given" : "Elliot", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Best", "given" : "Lael-Anson", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Granot", "given" : "Michal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pain", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2008", "8", "15" ] ] }, "note" : "NULL", "page" : "22-8", "title" : "Prediction of chronic post-operative pain: pre-operative DNIC testing identifies patients at risk.", "type" : "article-journal", "volume" : "138" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1302/0301-620X.90B2.19640", "ISSN" : "0301-620X", "PMID" : "18256082", "abstract" : "We suggest that different mechanisms underlie joint pain at rest and on movement in osteoarthritis and that separate assessment of these two features with a visual analogue scale (VAS) offers better information about the likely effect of a total knee replacement (TKR) on pain. The risk of persistent pain after TKR may relate to the degree of central sensitisation before surgery, which might be assessed by determining the pain threshold to an electrical stimulus created by a special tool, the Pain Matcher. Assessments were performed in 69 patients scheduled for TKR. At 18 months after operation, separate assessment of pain at rest and with movement was again carried out using a VAS in order to enable comparison of pre- and post-operative measurements. A less favourable outcome in terms of pain relief was observed for patients with a high pre-operative VAS score for pain at rest and a low pain threshold, both features which may reflect a central sensitisation mechanism.", "author" : [ { "dropping-particle" : "", "family" : "Lundblad", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kreicbergs", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jansson", "given" : "K A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of bone and joint surgery. British volume", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2008", "2", "1" ] ] }, "note" : "NULL", "page" : "166-71", "title" : "Prediction of persistent pain after total knee replacement for osteoarthritis.", "type" : "article-journal", "volume" : "90" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(100,101)", "plainTextFormattedCitation" : "(100,101)", "previouslyFormattedCitation" : "(100,101)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(100,101), and derive reduced analgesic effects from opioidsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0003-3022", "PMID" : "16732096", "abstract" : "BACKGROUND A variety of analgesics have been studied in the treatment of postherpetic neuralgia, with several medications demonstrating some degree of efficacy. However, existing trials have documented large individual differences in treatment responses, and it is important to identify patient characteristics that predict the analgesic effectiveness of particular interventions. Several animal studies have indicated that reduced basal nociceptive sensitivity, in the form of relatively high heat pain thresholds, is associated with greater opioid analgesia, but this finding has not been applied to human studies of opioid treatment for chronic pain. METHODS Using data from a previously published crossover trial of opioids and tricyclics in postherpetic neuralgia, the authors evaluated baseline thermal pain thresholds, assessed at a body site contralateral to the affected area, as a predictor of treatment responses. RESULTS During opioid treatment, a greater reduction in pain and higher ratings of pain relief were observed in patients with relatively higher heat pain thresholds at baseline. Baseline pain thresholds did not predict responses to tricyclics or placebo. Interestingly, other individual-difference variables such as age and baseline pain intensity also significantly predicted opioid responses (i.e., higher baseline pain and younger age were related to greater opioid-associated pain reduction, with nearly 20% of the variance in opioid analgesia explained by these two factors). CONCLUSIONS These findings, which will require replication, suggest that pretreatment assessment of heat pain sensitivity might prove useful in identifying those patients most likely to respond to opioids.", "author" : [ { "dropping-particle" : "", "family" : "Edwards", "given" : "Robert R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haythornthwaite", "given" : "Jennifer A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tella", "given" : "Prabhav", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Max", "given" : "Mitchell B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raja", "given" : "Srinivasa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Anesthesiology", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2006", "6" ] ] }, "note" : "NULL", "page" : "1243-8", "title" : "Basal heat pain thresholds predict opioid analgesia in patients with postherpetic neuralgia.", "type" : "article-journal", "volume" : "104" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(102)", "plainTextFormattedCitation" : "(102)", "previouslyFormattedCitation" : "(102)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(102). QST, along with other mechanistic-based techniques in CP patients was recently reviewed by Bouwense and colleaguesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3748/wjg.v21.i1.47", "ISSN" : "2219-2840", "PMID" : "25574079", "abstract" : "Pain in chronic pancreatitis (CP) shows similarities with other visceral pain syndromes (i.e., inflammatory bowel disease and esophagitis), which should thus be managed in a similar fashion. Typical causes of CP pain include increased intrapancreatic pressure, pancreatic inflammation and pancreatic/extrapancreatic complications. Unfortunately, CP pain continues to be a major clinical challenge. It is recognized that ongoing pain may induce altered central pain processing, e.g., central sensitization or pro-nociceptive pain modulation. When this is present conventional pain treatment targeting the nociceptive focus, e.g., opioid analgesia or surgical/endoscopic intervention, often fails even if technically successful. If central nervous system pain processing is altered, specific treatment targeting these changes should be instituted (e.g., gabapentinoids, ketamine or tricyclic antidepressants). Suitable tools are now available to make altered central processing visible, including quantitative sensory testing, electroencephalograpy and (functional) magnetic resonance imaging. These techniques are potentially clinically useful diagnostic tools to analyze central pain processing and thus define optimum management approaches for pain in CP and other visceral pain syndromes. The present review proposes a systematic mechanism-orientated approach to pain management in CP based on a holistic view of the mechanisms involved. Future research should address the circumstances under which central nervous system pain processing changes in CP, and how this is influenced by ongoing nociceptive input and therapies. Thus we hope to predict which patients are at risk for developing chronic pain or not responding to therapy, leading to improved treatment of chronic pain in CP and other visceral pain disorders.", "author" : [ { "dropping-particle" : "", "family" : "Bouwense", "given" : "Stefan A W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vries", "given" : "Marjan", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schreuder", "given" : "Luuk T W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olesen", "given" : "S\u00f8ren S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fr\u00f8kj\u00e6r", "given" : "Jens B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goor", "given" : "Harry", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "Oliver H G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "World journal of gastroenterology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2015", "1", "7" ] ] }, "page" : "47-59", "title" : "Systematic mechanism-orientated approach to chronic pancreatitis pain.", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(103)", "plainTextFormattedCitation" : "(103)", "previouslyFormattedCitation" : "(103)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(103); we refer the reader to their work for a more comprehensive overview. ?CP patients have documented hypoalgesia to visceral and somatic stimulation from tonic and phasic mechanical stimuli compared to healthy controlsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/01.meg.0000223903.70492.c5", "ISSN" : "0954-691X", "PMID" : "16772833", "abstract" : "OBJECTIVES To gain more information of the pain mechanisms in chronic pancreatitis we applied standardized experimental pain stimulation of the duodenum, oesophagus and the skin in 12 healthy controls and 13 patients with chronic pancreatitis and typical pain attacks. METHODS Using endoscopy a guide wire was positioned into the horizontal part of the duodenum, and a probe with a distal balloon was introduced over the guide wire. Mechanical stimuli were given as tonic (38 ml/min) or phasic (increasing volume steps of 5 ml delivered for 60 s) distensions of the balloon. After stimulation of the duodenum, the distal oesophagus was stimulated with the same protocol. Finally, the skin was stimulated with 'single and repeated burst' electrical stimuli reflecting activation of peripheral and central pain mechanisms. RESULTS The stimuli reliably evoked both painful and non-painful local and referred sensations. The patients had hyposensitivity to both tonic and phasic mechanical stimuli of the duodenum and the oesophagus (P=0.001). Hypoalgesia was also observed to single and repeated electrical skin stimuli in the patients, most evident for repeated stimuli (P=0.001). The evoked referred pain did not differ between the groups, but the patients used on average more words from the McGill Pain Questionnaire to describe the pain evoked in the duodenum (P=0.02). CONCLUSIONS Generalized hypoalgesia to experimental visceral and somatic stimulations was found in chronic pancreatitis. The findings suggest that the activation and modulation of central mechanisms is fundamental in pancreatic pain, and future studies should address the effect of analgesics with central effects in the treatment of these patients.", "author" : [ { "dropping-particle" : "", "family" : "Dimcevski", "given" : "Georg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schipper", "given" : "Klaus P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tage-Jensen", "given" : "Ulrik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Funch-Jensen", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Krarup", "given" : "Anne L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Toft", "given" : "Egon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorsgaard", "given" : "Niels", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arendt-Nielsen", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European journal of gastroenterology & hepatology", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2006", "7" ] ] }, "note" : "NULL", "page" : "755-64", "title" : "Hypoalgesia to experimental visceral and somatic stimulation in painful chronic pancreatitis.", "type" : "article-journal", "volume" : "18" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(104)", "plainTextFormattedCitation" : "(104)", "previouslyFormattedCitation" : "(104)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(104), hypersensitivity to mechanical stimulation of the skinADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/mpa.0b013e31805c1762", "ISSN" : "1536-4828", "PMID" : "17575541", "abstract" : "OBJECTIVES Comprehensive experimental methods are of major relevance assessing pain mechanisms in patients with chronic pain. Chronic pancreatitis is thought to involve the sensory response in other visceral organs and somatic tissue. We, therefore, aimed at exploring the pain mechanisms in chronic pancreatitis (CP) using a multimodal and multitissue stimulation approach. METHODS Ten patients (mean age, 50 years) with CP and 13 healthy controls (mean age, 35 years) participated. None of the patients took analgesics regularly. All were exposed to multimodal (mechanical, thermal, and electrical) experimental pain in the skin, muscles, and esophagus. RESULTS The patients were hyposensitive to mechanical stimulations of the skin (P = 0.001), but there were no differences in the pain to thermal and electrical stimulations. In the muscle and esophagus, no differences in pain thresholds were found. The difference between single and repeated stimulations reflecting the degree of central sensitization was 17% in controls and 36% in patients (P = 0.001). The referred pain area to electrical stimulation was 30.1 cm2 in the patients and 7.7 cm2 for the controls (P = 0.02). CONCLUSIONS The findings suggest that the balance among central hyperexcitability, neuroplastic changes, and descending pain-modulating pathways may explain the pain response to experimental multimodal stimulations in CP. This will likely also reflect the clinical pain mechanisms and may have important impact in selection of treatment, where drugs with potential effects on these mechanisms should be used.", "author" : [ { "dropping-particle" : "", "family" : "Dimcevski", "given" : "Georg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Staahl", "given" : "Camilla", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andersen", "given" : "S\u00f8ren Due", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorsgaard", "given" : "Niels", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Funch-Jensen", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arendt-Nielsen", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn Mohr", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreas", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2007", "7" ] ] }, "note" : "NULL", "page" : "22-9", "title" : "Assessment of experimental pain from skin, muscle, and esophagus in patients with chronic pancreatitis.", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(105)", "plainTextFormattedCitation" : "(105)", "previouslyFormattedCitation" : "(105)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(105), and higher cortical activity than controls in specific bands when the esophagus is electrically stimulated to pain threshold, suggesting involvement of neuropathic?pain?mechanismsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1007-9327", "PMID" : "18609686", "abstract" : "AIM To prove the hypothesis that patients with chronic pancreatitis would show increased theta activity during painful visceral stimulation. METHODS Eight patients and 12 healthy controls underwent an experiment where the esophagus was electrically stimulated at the pain threshold using a nasal endoscope. The electroencephalogram (EEG) was recorded from 64 surface electrodes and \"topographic matching pursuit\" was used to extract the EEG information in the early brain activation after stimulation. RESULTS A major difference between controls and patients were seen in delta and theta bands, whereas there were only minor differences in other frequency bands. In the theta band, the patients showed higher activity than controls persisting throughout the 450 ms of analysis with synchronous brain activation between the channels. The main theta components oscillated with 4.4 Hz in the patients and 5.5 Hz in the controls. The energy in the delta (0.5-3.5 Hz) band was higher in the controls, whereas the patients only showed scattered activity in this band. CONCLUSION The differences in the theta band indicate that neuropathic pain mechanisms are involved in chronic pancreatitis. This has important implications for the understanding and treatment of pain in these patients, which should be directed against drugs with effects on neuropathic pain disorders.", "author" : [ { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gratkowski", "given" : "Maciej", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sami", "given" : "Saber A K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dimcevski", "given" : "Georg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Funch-Jensen", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arendt-Nielsen", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "World journal of gastroenterology", "id" : "ITEM-1", "issue" : "25", "issued" : { "date-parts" : [ [ "2008", "7", "7" ] ] }, "note" : "NULL", "page" : "4020-7", "title" : "Is the pain in chronic pancreatitis of neuropathic origin? Support from EEG studies during experimental pain.", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(106)", "plainTextFormattedCitation" : "(106)", "previouslyFormattedCitation" : "(106)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(106).?Central sensitization in CP was hypothesized and examined using QST over a decade agoADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.ejpain.2005.06.006", "ISSN" : "1090-3801", "PMID" : "16087373", "abstract" : "BACKGROUND The pain of chronic pancreatitis remains challenging to manage, with treatment all too often being unsuccessful. A main reason for this is lacking understanding of underlying mechanisms of chronic pain in these patients. AIM To document, using somatic quantitative sensory testing, changes in central nervous system processing (neuroplasticity) associated with chronic pancreatitis pain and thus gain insight into underlying pain mechanisms. PATIENTS AND METHODS We studied 10 chronic pancreatitis patients on stable opioid analgesic medication. Ten matched surgical patients without pain served as controls. Pain verbal numeric rating scores (NRS) and thresholds to electric skin stimulation and pressure pain were measured in dermatomes T10 (pancreatic area), C5, T4, L1 and L4. RESULTS The pancreatitis patients had a median NRS pain score of 5 (range 3-8). Electric sensation and pain thresholds were significantly increased in the pancreatic region, tending to be more so in female pancreatitis patients. Pressure pain thresholds were significantly lower in pancreatitis patients than in controls, with men tending towards greater generalised relative hyperalgesia than women. CONCLUSIONS Chronic pancreatitis patients show pronounced generalised deep hyperalgesia that is present despite opioid therapy. These signs, consistent with central sensitisation, appear relatively more prominent in men than women. There is also evidence suggesting that women may have a better segmental inhibitory response than men, possibly explaining their relatively less prominent generalised deep tissue hyperalgesia compared to men.", "author" : [ { "dropping-particle" : "", "family" : "Buscher", "given" : "Hessel C J L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "Oliver H G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goor", "given" : "Harry", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "European journal of pain (London, England)", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2006", "5" ] ] }, "note" : "NULL", "page" : "363-70", "title" : "Chronic pancreatitis patients show hyperalgesia of central origin: a pilot study.", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(37)", "plainTextFormattedCitation" : "(37)", "previouslyFormattedCitation" : "(37)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(37) and has received additional attention, evaluation and documentation through assessment of conditioned pain modulation and widespread painADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1053/j.gastro.2007.01.037", "ISSN" : "00165085", "PMID" : "17408654", "abstract" : "BACKGROUND & AIMS In various chronic pain conditions cortical reorganization seems to play a role in the manifestations. The aim of this study was to investigate cortical reorganization in patients with pain caused by chronic pancreatitis. METHODS Twelve healthy subjects and 10 patients with chronic pancreatitis were included. The esophagus, stomach, and duodenum were stimulated electrically at the pain threshold using a nasal endoscope. The electroencephalogram was recorded from 64 surface electrodes and event-related brain potentials (EPs) were obtained. RESULTS As compared with healthy subjects, the patient group showed decreased latencies of the early EP components (N1, P < .001; P1, P = .02), which is thought to reflect the exogenous brain pain processing specifically. Source analysis showed that the dipolar activities corresponding to the early EPs were located consistently in the bilateral insula, in the anterior cingulate gyrus, and in the bilateral secondary somatosensory area. The bilateral insular dipoles were localized more medial in the patient group than in the healthy subjects after stimulation of all 3 gut segments (P < .01). There also were changes in the cingulate cortex where the neuronal source was more posterior in patients than in controls to stimulation of the esophagus (P < .05). CONCLUSIONS The findings indicate that pain in chronic pancreatitis leads to changes in cortical projections of the nociceptive system. Such findings also have been described in somatic pain disorders, among them neuropathic pain. Taken together with the clinical data this suggests a neuropathic component in pancreatic pain, which may influence the approach to treatment.", "author" : [ { "dropping-particle" : "", "family" : "Dimcevski", "given" : "Georg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sami", "given" : "Saber A.K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Funch\u2013Jensen", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pera", "given" : "Domenica", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valeriani", "given" : "Massimiliano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arendt\u2013Nielsen", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2007", "4" ] ] }, "page" : "1546-1556", "title" : "Pain in Chronic Pancreatitis: The Role of Reorganization in the Central Nervous System", "type" : "article-journal", "volume" : "132" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.cgh.2010.03.005", "ISSN" : "1542-7714", "PMID" : "20304100", "abstract" : "BACKGROUND & AIMS Pain is a prominent symptom in chronic pancreatitis (CP), but the underlying mechanisms are incompletely understood. We investigated the role of descending pain modulation from supraspinal structures as well as central nervous system sensitization in patients with pain from CP. METHODS Twenty-five patients with CP and 15 healthy volunteers were included. Descending pain modulation was investigated by diffuse noxious inhibitory control (a descending inhibitory response after conditioning stimulation). Central pain processing was investigated as the perceptual responses to multimodal (electrical, thermal, and mechanical) stimulations of the rectosigmoid and evoked brain potentials after electrical stimulation of the rectosigmoid. RESULTS Compared with healthy volunteers, the efficacy of diffuse noxious inhibitory control was reduced in patients with CP (13% +/- 21% vs 39% +/- 22%, respectively; F = 3.8; P = .01); central sensitization was indicated by remote hyperalgesia in the rectosigmoid to electrical stimulation (21 +/- 15 mA vs 27 +/- 15 mA; F = 6.2; P = .02) and heat stimulation (51 degrees C +/- 5 degrees C vs 53 degrees C +/- 4 degrees C; F = 5.9; P = .02). Compared with controls, patients with CP had increased latency of the early P1 peak to rectosigmoid stimulation (85 +/- 21 ms vs 108 +/- 28 ms, respectively; P = .02), possibly reflecting reorganization of central pain pathways. CONCLUSIONS Patients with CP have impairments in inhibitory pain modulation and evidence of central sensitization. Treatment of their pain therefore should focus not only on the pancreas, but also on descending pain modulation from supraspinal structures and central nervous system sensitization.", "author" : [ { "dropping-particle" : "", "family" : "Olesen", "given" : "S\u00f8ren Schou", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brock", "given" : "Christina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Krarup", "given" : "Anne Lund", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Funch-Jensen", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arendt-Nielsen", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "Oliver H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn Mohr", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association", "id" : "ITEM-2", "issue" : "8", "issued" : { "date-parts" : [ [ "2010", "8" ] ] }, "note" : "NULL", "page" : "724-30", "title" : "Descending inhibitory pain modulation is impaired in patients with chronic pancreatitis.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(36,38)", "plainTextFormattedCitation" : "(36,38)", "previouslyFormattedCitation" : "(36,38)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(36,38), pain facilitation and referred pain to electrical stimulationADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/mpa.0b013e31805c1762", "ISSN" : "1536-4828", "PMID" : "17575541", "abstract" : "OBJECTIVES Comprehensive experimental methods are of major relevance assessing pain mechanisms in patients with chronic pain. Chronic pancreatitis is thought to involve the sensory response in other visceral organs and somatic tissue. We, therefore, aimed at exploring the pain mechanisms in chronic pancreatitis (CP) using a multimodal and multitissue stimulation approach. METHODS Ten patients (mean age, 50 years) with CP and 13 healthy controls (mean age, 35 years) participated. None of the patients took analgesics regularly. All were exposed to multimodal (mechanical, thermal, and electrical) experimental pain in the skin, muscles, and esophagus. RESULTS The patients were hyposensitive to mechanical stimulations of the skin (P = 0.001), but there were no differences in the pain to thermal and electrical stimulations. In the muscle and esophagus, no differences in pain thresholds were found. The difference between single and repeated stimulations reflecting the degree of central sensitization was 17% in controls and 36% in patients (P = 0.001). The referred pain area to electrical stimulation was 30.1 cm2 in the patients and 7.7 cm2 for the controls (P = 0.02). CONCLUSIONS The findings suggest that the balance among central hyperexcitability, neuroplastic changes, and descending pain-modulating pathways may explain the pain response to experimental multimodal stimulations in CP. This will likely also reflect the clinical pain mechanisms and may have important impact in selection of treatment, where drugs with potential effects on these mechanisms should be used.", "author" : [ { "dropping-particle" : "", "family" : "Dimcevski", "given" : "Georg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Staahl", "given" : "Camilla", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andersen", "given" : "S\u00f8ren Due", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorsgaard", "given" : "Niels", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Funch-Jensen", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arendt-Nielsen", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn Mohr", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreas", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2007", "7" ] ] }, "note" : "NULL", "page" : "22-9", "title" : "Assessment of experimental pain from skin, muscle, and esophagus in patients with chronic pancreatitis.", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(105)", "plainTextFormattedCitation" : "(105)", "previouslyFormattedCitation" : "(105)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(105), repeated electrical stimulation to the skin (reflective of pain facilitation)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/01.meg.0000223903.70492.c5", "ISSN" : "0954-691X", "PMID" : "16772833", "abstract" : "OBJECTIVES To gain more information of the pain mechanisms in chronic pancreatitis we applied standardized experimental pain stimulation of the duodenum, oesophagus and the skin in 12 healthy controls and 13 patients with chronic pancreatitis and typical pain attacks. METHODS Using endoscopy a guide wire was positioned into the horizontal part of the duodenum, and a probe with a distal balloon was introduced over the guide wire. Mechanical stimuli were given as tonic (38 ml/min) or phasic (increasing volume steps of 5 ml delivered for 60 s) distensions of the balloon. After stimulation of the duodenum, the distal oesophagus was stimulated with the same protocol. Finally, the skin was stimulated with 'single and repeated burst' electrical stimuli reflecting activation of peripheral and central pain mechanisms. RESULTS The stimuli reliably evoked both painful and non-painful local and referred sensations. The patients had hyposensitivity to both tonic and phasic mechanical stimuli of the duodenum and the oesophagus (P=0.001). Hypoalgesia was also observed to single and repeated electrical skin stimuli in the patients, most evident for repeated stimuli (P=0.001). The evoked referred pain did not differ between the groups, but the patients used on average more words from the McGill Pain Questionnaire to describe the pain evoked in the duodenum (P=0.02). CONCLUSIONS Generalized hypoalgesia to experimental visceral and somatic stimulations was found in chronic pancreatitis. The findings suggest that the activation and modulation of central mechanisms is fundamental in pancreatic pain, and future studies should address the effect of analgesics with central effects in the treatment of these patients.", "author" : [ { "dropping-particle" : "", "family" : "Dimcevski", "given" : "Georg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schipper", "given" : "Klaus P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tage-Jensen", "given" : "Ulrik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Funch-Jensen", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Krarup", "given" : "Anne L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Toft", "given" : "Egon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorsgaard", "given" : "Niels", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arendt-Nielsen", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European journal of gastroenterology & hepatology", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2006", "7" ] ] }, "note" : "NULL", "page" : "755-64", "title" : "Hypoalgesia to experimental visceral and somatic stimulation in painful chronic pancreatitis.", "type" : "article-journal", "volume" : "18" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(104)", "plainTextFormattedCitation" : "(104)", "previouslyFormattedCitation" : "(104)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(104), as well as positive trials of pharmaceutical treatments known to impact central sensitizationADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0057963", "ISSN" : "1932-6203", "PMID" : "23469256", "abstract" : "BACKGROUND A major problem in pain medicine is the lack of knowledge about which treatment suits a specific patient. We tested the ability of quantitative sensory testing to predict the analgesic effect of pregabalin and placebo in patients with chronic pancreatitis. METHODS Sixty-four patients with painful chronic pancreatitis received pregabalin (150-300 mg BID) or matching placebo for three consecutive weeks. Analgesic effect was documented in a pain diary based on a visual analogue scale. Responders were defined as patients with a reduction in clinical pain score of 30% or more after three weeks of study treatment compared to baseline recordings. Prior to study medication, pain thresholds to electric skin and pressure stimulation were measured in dermatomes T10 (pancreatic area) and C5 (control area). To eliminate inter-subject differences in absolute pain thresholds an index of sensitivity between stimulation areas was determined (ratio of pain detection thresholds in pancreatic versus control area, ePDT ratio). Pain modulation was recorded by a conditioned pain modulation paradigm. A support vector machine was used to screen sensory parameters for their predictive power of pregabalin efficacy. RESULTS The pregabalin responders group was hypersensitive to electric tetanic stimulation of the pancreatic area (ePDT ratio 1.2 (0.9-1.3)) compared to non-responders group (ePDT ratio: 1.6 (1.5-2.0)) (P\u200a=\u200a0.001). The electrical pain detection ratio was predictive for pregabalin effect with a classification accuracy of 83.9% (P\u200a=\u200a0.007). The corresponding sensitivity was 87.5% and specificity was 80.0%. No other parameters were predictive of pregabalin or placebo efficacy. CONCLUSIONS The present study provides first evidence that quantitative sensory testing predicts the analgesic effect of pregabalin in patients with painful chronic pancreatitis. The method can be used to tailor pain medication based on patient's individual sensory profile and thus comprises a significant step towards personalized pain medicine.", "author" : [ { "dropping-particle" : "", "family" : "Olesen", "given" : "S\u00f8ren S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graversen", "given" : "Carina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bouwense", "given" : "Stefan A W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goor", "given" : "Harry", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "Oliver H G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "editor" : [ { "dropping-particle" : "", "family" : "Miaskowski", "given" : "Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2013", "3", "1" ] ] }, "note" : "NULL", "page" : "e57963", "title" : "Quantitative sensory testing predicts pregabalin efficacy in painful chronic pancreatitis.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1371/journal.pone.0042096", "ISSN" : "1932-6203", "PMID" : "22879908", "abstract" : "BACKGROUND Intense abdominal pain is the dominant feature of chronic pancreatitis. During the disease changes in central pain processing, e.g. central sensitization manifest as spreading hyperalgesia, can result from ongoing nociceptive input. The aim of the present study is to evaluate the effect of pregabalin on pain processing in chronic pancreatitis as assessed by quantitative sensory testing (QST). METHODS This randomized, double-blind, placebo-controlled trial evaluated effects of pregabalin on pain processing. QST was used to quantify pain processing by measuring thresholds to painful electrical and pressure stimulation in six body dermatomes. Descending endogenous pain modulation was quantified using the conditioned pain modulation (CPM) paradigm to elicit a DNIC (diffuse noxious inhibitory controls) response. The main effect parameter was the change in the sum of all body pain threshold values after three weeks of study treatment versus baseline values between both treatment groups. RESULTS 64 patients were analyzed. No differences in change in sum of pain thresholds were present for pregabalin vs. placebo after three weeks of treatment. For individual dermatomes, change vs. baseline pain thresholds was significantly greater in pregabalin vs. placebo patients for electric pain detection threshold in C5 (P = 0.005), electric pain tolerance threshold in C5 (P = 0.04) and L1 (P = 0.05), and pressure pain tolerance threshold in T4 (P = 0.004). No differences were observed between pregabalin and placebo regarding conditioned pain modulation. CONCLUSION Our study provides first evidence that pregabalin has moderate inhibitory effects on central sensitization manifest as spreading hyperalgesia in chronic pancreatitis patients. These findings suggest that QST can be of clinical use for monitoring pain treatments in the context of chronic pain. TRIAL REGISTRATION NCT00755573.", "author" : [ { "dropping-particle" : "", "family" : "Bouwense", "given" : "Stefan A W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olesen", "given" : "S\u00f8ren S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Poley", "given" : "Jan-Werner", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goor", "given" : "Harry", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "Oliver H G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "editor" : [ { "dropping-particle" : "", "family" : "Eldabe", "given" : "Sam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-2", "issue" : "8", "issued" : { "date-parts" : [ [ "2012", "8", "6" ] ] }, "note" : "NULL", "page" : "e42096", "title" : "Effects of pregabalin on central sensitization in patients with chronic pancreatitis in a randomized, controlled trial.", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1097/AAP.0b013e3182177022", "ISSN" : "1532-8651", "PMID" : "21490522", "abstract" : "BACKGROUND AND OBJECTIVES Upper abdominal pain is a dominant feature of chronic pancreatitis. A key phenomenon in this context is hyperalgesia, typically associated with N-methyl-d-aspartate receptor activation. This exploratory study evaluates acute effects of S-ketamine, a noncompetitive N-methyl-d-aspartate antagonist, in modulating generalized hyperalgesia in chronic pancreatitis pain. METHODS In a blinded crossover trial, 10 chronic pancreatitis pain patients received S-ketamine for 3 hrs at 2 \u03bcg \u00b7 kg \u00b7 min or placebo infusion at an equivalent rate in randomized order. Clinical pain was assessed via visual analog scale (VAS) and short Dutch Language Version McGill Pain Questionnaire (sf-MPQ-DLV). Pressure pain thresholds (PPTs) were measured in dermatome C5, T4, dorsal T10, L1, and L4, and the sum of PPTs (SOPPT) calculated before, at end of, and after infusion. RESULTS Nine patients completed the study. Median pain VAS before infusion was 29 mm at rest, 32 mm during activity; sf-MPQ-DLV score was 4. For the S-ketamine session median SOPPT change at infusion end was significantly higher than in the placebo session (218; interquartile range [IQR], 116-527, versus -123 [IQR, -330 to 24]; P = 0.005) and significant versus preinfusion values (2109 [IQR, 964-3035] vs 1914 [IQR, 842-2884]; P = 0.03). The SOPPT was unchanged versus preinfusion values and similar between groups at 1 hr after infusion end. No significant changes in VAS and sf-MPQ-DLV occurred. CONCLUSIONS S-ketamine infusion is more effective than placebo in increasing PPTs in chronic pancreatitis pain patients immediately after infusion. This effect did not outlast the infusion. Further research is warranted into S-ketamine use for reducing generalized hyperalgesia and chronic pancreatitis pain.", "author" : [ { "dropping-particle" : "", "family" : "Bouwense", "given" : "Stefan A W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buscher", "given" : "Hessel C J L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goor", "given" : "Harry", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "Oliver H G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Regional anesthesia and pain medicine", "id" : "ITEM-3", "issue" : "3", "issued" : { "date-parts" : [ [ "2011", "5" ] ] }, "page" : "303-7", "title" : "S-ketamine modulates hyperalgesia in patients with chronic pancreatitis pain.", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(107\u2013109)", "plainTextFormattedCitation" : "(107\u2013109)", "previouslyFormattedCitation" : "(107\u2013109)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(107–109). For example, QST, being frequently employed to evaluate treatment responses, evaluated among CP patients, was found to elicit increased electrical pain detection and tolerance, as well as pressure pain tolerance following a three-week course of pregabalin as compared to placebo, suggesting inhibitory effects of the hyperalgesic spreading component of central sensitizationADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0042096", "ISSN" : "1932-6203", "PMID" : "22879908", "abstract" : "BACKGROUND Intense abdominal pain is the dominant feature of chronic pancreatitis. During the disease changes in central pain processing, e.g. central sensitization manifest as spreading hyperalgesia, can result from ongoing nociceptive input. The aim of the present study is to evaluate the effect of pregabalin on pain processing in chronic pancreatitis as assessed by quantitative sensory testing (QST). METHODS This randomized, double-blind, placebo-controlled trial evaluated effects of pregabalin on pain processing. QST was used to quantify pain processing by measuring thresholds to painful electrical and pressure stimulation in six body dermatomes. Descending endogenous pain modulation was quantified using the conditioned pain modulation (CPM) paradigm to elicit a DNIC (diffuse noxious inhibitory controls) response. The main effect parameter was the change in the sum of all body pain threshold values after three weeks of study treatment versus baseline values between both treatment groups. RESULTS 64 patients were analyzed. No differences in change in sum of pain thresholds were present for pregabalin vs. placebo after three weeks of treatment. For individual dermatomes, change vs. baseline pain thresholds was significantly greater in pregabalin vs. placebo patients for electric pain detection threshold in C5 (P = 0.005), electric pain tolerance threshold in C5 (P = 0.04) and L1 (P = 0.05), and pressure pain tolerance threshold in T4 (P = 0.004). No differences were observed between pregabalin and placebo regarding conditioned pain modulation. CONCLUSION Our study provides first evidence that pregabalin has moderate inhibitory effects on central sensitization manifest as spreading hyperalgesia in chronic pancreatitis patients. These findings suggest that QST can be of clinical use for monitoring pain treatments in the context of chronic pain. TRIAL REGISTRATION NCT00755573.", "author" : [ { "dropping-particle" : "", "family" : "Bouwense", "given" : "Stefan A W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olesen", "given" : "S\u00f8ren S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Poley", "given" : "Jan-Werner", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goor", "given" : "Harry", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "Oliver H G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "editor" : [ { "dropping-particle" : "", "family" : "Eldabe", "given" : "Sam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2012", "8", "6" ] ] }, "note" : "NULL", "page" : "e42096", "title" : "Effects of pregabalin on central sensitization in patients with chronic pancreatitis in a randomized, controlled trial.", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(108)", "plainTextFormattedCitation" : "(108)", "previouslyFormattedCitation" : "(108)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(108). Additionally, oxycodone was found to be more effective than placebo and morphine on mechanically and thermally evoked pain stimulation as well as oesophageal heat painADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/00365520601014414", "ISSN" : "0036-5521", "PMID" : "17354119", "abstract" : "OBJECTIVE Animal experiments and clinical observations have indicated a different working profile of oxycodone compared to morphine, and it has previously been shown that oxycodone attenuates visceral pain better than morphine. The objective of this study was to test the effects of oxycodone and morphine on experimental pain in patients with pain caused by chronic pancreatitis. MATERIAL AND METHODS Ten patients took part in this blinded, cross-over study. The analgesic effects of morphine (30 mg, oral), oxycodone (15 mg, oral) and placebo were tested against multimodal (mechanical, thermal and electrical) experimental pain in the skin, muscles and oesophagus. Pain was assessed at baseline and 30, 60 and 90 min after drug administration. RESULTS In the skin and muscles, oxycodone was more effective than placebo and morphine on mechanically (skin: F=12.4, p<0.001, muscle: F=11.0, p<0.001) and thermally (skin: F=8.5, p<0.001) evoked pain. In oesophageal heat pain, the effect of morphine was equal to that of placebo, while oxycodone attenuated pain better than both morphine and placebo (F=9.5, p<0.001). Both morphine and oxycodone were more effective in attenuating mechanical pain in the oesophagus than placebo (F=8.6, p<0.001). After electrical stimulation no differences were seen between the opioids and placebo in any tissue studied. CONCLUSIONS Oxycodone was a stronger analgesic than morphine in several pain modalities in the skin, muscle and oesophagus.", "author" : [ { "dropping-particle" : "", "family" : "Staahl", "given" : "Camilla", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dimcevski", "given" : "Georg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andersen", "given" : "S\u00f8ren Due", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorsgaard", "given" : "Niels", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Christrup", "given" : "Lona L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arendt-Nielsen", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn Mohr", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of gastroenterology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2007", "3", "8" ] ] }, "note" : "NULL", "page" : "383-90", "title" : "Differential effect of opioids in patients with chronic pancreatitis: an experimental pain study.", "type" : "article-journal", "volume" : "42" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(110)", "plainTextFormattedCitation" : "(110)", "previouslyFormattedCitation" : "(110)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(110). A particularly elegant study recently found that QST responses were able to predict the analgesic efficacy of pregabalin in CP patientsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0057963", "ISSN" : "1932-6203", "PMID" : "23469256", "abstract" : "BACKGROUND A major problem in pain medicine is the lack of knowledge about which treatment suits a specific patient. We tested the ability of quantitative sensory testing to predict the analgesic effect of pregabalin and placebo in patients with chronic pancreatitis. METHODS Sixty-four patients with painful chronic pancreatitis received pregabalin (150-300 mg BID) or matching placebo for three consecutive weeks. Analgesic effect was documented in a pain diary based on a visual analogue scale. Responders were defined as patients with a reduction in clinical pain score of 30% or more after three weeks of study treatment compared to baseline recordings. Prior to study medication, pain thresholds to electric skin and pressure stimulation were measured in dermatomes T10 (pancreatic area) and C5 (control area). To eliminate inter-subject differences in absolute pain thresholds an index of sensitivity between stimulation areas was determined (ratio of pain detection thresholds in pancreatic versus control area, ePDT ratio). Pain modulation was recorded by a conditioned pain modulation paradigm. A support vector machine was used to screen sensory parameters for their predictive power of pregabalin efficacy. RESULTS The pregabalin responders group was hypersensitive to electric tetanic stimulation of the pancreatic area (ePDT ratio 1.2 (0.9-1.3)) compared to non-responders group (ePDT ratio: 1.6 (1.5-2.0)) (P\u200a=\u200a0.001). The electrical pain detection ratio was predictive for pregabalin effect with a classification accuracy of 83.9% (P\u200a=\u200a0.007). The corresponding sensitivity was 87.5% and specificity was 80.0%. No other parameters were predictive of pregabalin or placebo efficacy. CONCLUSIONS The present study provides first evidence that quantitative sensory testing predicts the analgesic effect of pregabalin in patients with painful chronic pancreatitis. The method can be used to tailor pain medication based on patient's individual sensory profile and thus comprises a significant step towards personalized pain medicine.", "author" : [ { "dropping-particle" : "", "family" : "Olesen", "given" : "S\u00f8ren S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graversen", "given" : "Carina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bouwense", "given" : "Stefan A W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goor", "given" : "Harry", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "Oliver H G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "editor" : [ { "dropping-particle" : "", "family" : "Miaskowski", "given" : "Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2013", "3", "1" ] ] }, "note" : "NULL", "page" : "e57963", "title" : "Quantitative sensory testing predicts pregabalin efficacy in painful chronic pancreatitis.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(107)", "plainTextFormattedCitation" : "(107)", "previouslyFormattedCitation" : "(107)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(107) with solid classification accuracy (84%).Biomarkers for pancreatic pain and pain severitySeveral studies from the same group of investigators suggest a correlation between inflammatory, neuropathological and expression of certain biological factors and severity of painADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.bpg.2007.10.016", "ISSN" : "1521-6918", "PMID" : "18206811", "abstract" : "Abdominal pain is an important clinical symptom in pancreatic diseases. There is increasing evidence that pain in chronic pancreatitis and pancreatic cancer is triggered by pancreatic neuropathy. Damage to intrapancreatic nerves seems to support the maintenance and exacerbation of neuropathic pain. In chronic pancreatitis, intrapancreatic nerves are invaded by immune cells. This observation led to the hypothesis that neuro-immune interactions play a role in the pathogenesis of chronic pancreatitis and the accompanying abdominal pain syndrome. Similarly, pancreatic cancer cells infiltrate the perineurium of local nerves, which may in part explain the severe pain experienced by the patients. Furthermore, perineural invasion extending into extrapancreatic nerves may preclude curative resection and thus often leads to local recurrence. In recent years, the involvement of a variety of neurotrophins and neuropeptides in the pathogenesis of pancreatic pain was discovered. This review summarises recent data on the mechanisms of neuropathy and pain generation in pancreatic disorders.", "author" : [ { "dropping-particle" : "", "family" : "Ceyhan", "given" : "G\u00fcralp O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Michalski", "given" : "Christoph W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Demir", "given" : "Ihsan E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "M\u00fcller", "given" : "Michael W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Friess", "given" : "Helmut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Best practice & research. Clinical gastroenterology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2008", "2" ] ] }, "note" : "NULL", "page" : "31-44", "title" : "Pancreatic pain.", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(111)", "plainTextFormattedCitation" : "(111)", "previouslyFormattedCitation" : "(111)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(111). However, this is based on access to resected pancreatic tissue and so is not a practical biomarker. On the other hand, there is some promise in analysing pancreatic juice obtained at endoscopy for cytokines and small molecules- elevated levels of PGE2 have recently been found in the pancreatic secretions of patients with early chronic pancreatitis who have significant pain but no clear structural abnormalitiesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ctg.2014.23", "ISSN" : "2155-384X", "PMID" : "25630864", "abstract" : "OBJECTIVES Chronic pancreatitis (CP) may be difficult to diagnose in early stages. We aimed to measure pancreatic juice (PJ) prostaglandin E2 (PGE2) concentrations to determine whether they are elevated in CP and improve diagnosis of early disease. METHODS We measured PJ PGE2 in 10 patients with established CP, 25 patients who met criteria for \"minimal change\" chronic pancreatitis (MCCP), and 10 normal control participants. RESULTS Median PJ PGE2 was elevated in CP (307\u2009pg/ml, IQR (249-362)) and MCCP (568\u2009pg/ml, (418-854)) compared with normal controls (104\u2009pg/ml, (68-206)) (P\u2264 0.001). Area under receiving operator curve (AUROC) for diagnosis of CP and MCCP was 0.9 and 0.62, respectively, for PJ bicarbonate concentration alone; AUROC was 1.0 and 0.94 for the combination of PJ bicarbonate and PGE2 concentrations. CONCLUSIONS PJ PGE2 appears to be a biomarker for CP and is elevated in both established and \"minimal change\" chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Abu Dayyeh", "given" : "Barham K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Conwell", "given" : "Darwin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buttar", "given" : "Navtej S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kadilaya", "given" : "Vivek", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hart", "given" : "Philip A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baumann", "given" : "Nikola A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bick", "given" : "Benjamin L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chari", "given" : "Suresh T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chowdhary", "given" : "Sonia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clain", "given" : "Jonathan E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gleeson", "given" : "Ferga C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Linda S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Levy", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pearson", "given" : "Randall K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Petersen", "given" : "Bret T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rajan", "given" : "Elizabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steen", "given" : "Hanno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suleiman", "given" : "Shadeah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banks", "given" : "Peter A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vege", "given" : "Santhi S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Topazian", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical and translational gastroenterology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2015", "1", "29" ] ] }, "note" : "NULL", "page" : "e72", "title" : "Pancreatic juice prostaglandin e2 concentrations are elevated in chronic pancreatitis and improve detection of early disease.", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(23)", "plainTextFormattedCitation" : "(23)", "previouslyFormattedCitation" : "(23)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(23). Further studies are needed to validate this and other molecules in a broad spectrum of patients. Finally, there are several CNS markers that may be affected in CP and perhaps provide a so-called biomarker for pain in this condition. Electroencephalograpy (EEG) in patients with CP show functional changes suggesting a maladaptive pain responseADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2147/JPR.S50919", "ISSN" : "1178-7090", "PMID" : "24379694", "abstract" : "OBJECTIVES Electroencephalography (EEG) may be a promising source of physiological biomarkers accompanying chronic pain. Several studies in patients with chronic neuropathic pain have reported alterations in central pain processing, manifested as slowed EEG rhythmicity and increased EEG power in the brain's resting state. We aimed to investigate novel potential markers of chronic pain in the resting state EEG of patients with chronic pancreatitis. PARTICIPANTS Resting state EEG data from 16 patients with persistent abdominal pain due to chronic pancreatitis (CP) were compared to data from healthy controls matched for age, sex and education. METHODS The peak alpha frequency (PAF) and power amplitude in the alpha band (7.5-13 Hz) were compared between groups in four regions of interest (frontal, central, parietal, and occipital) and were correlated with pain duration. RESULTS The average PAF was lowered in CP patients compared with that in healthy controls, observed as a statistically significant between-group effect (mean 9.9 versus 9.5 Hz; P=0.049). Exploratory post hoc analysis of average PAF per region of interest revealed a significant difference, particularly in the parietal and occipital regions. In addition, we observed a significant correlation between pain duration and PAF and showed increased shifts in PAF with longer pain durations. No significant group differences were found in peak power amplitudes. CONCLUSION CP pain is associated with alterations in spontaneous brain activity, observed as a shift toward lower PAF. This shift correlates with the duration of pain, which demonstrates that PAF has the potential to be a clinically feasible biomarker for chronic pain. These findings could be helpful for assisting diagnosis, establishing optimal treatment, and studying efficacy of new therapeutic agents in chronic pain patients.", "author" : [ { "dropping-particle" : "", "family" : "Vries", "given" : "Marjan", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "Oliver Hg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "LA", "family" : "Jongsma", "given" : "Marijtje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Broeke", "given" : "Emanuel N", "non-dropping-particle" : "van den", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arns", "given" : "Martijn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goor", "given" : "Harry", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rijn", "given" : "Clementina M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of pain research", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013", "11", "25" ] ] }, "note" : "NULL", "page" : "815-24", "title" : "Altered resting state EEG in chronic pancreatitis patients: toward a marker for chronic pain.", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1097/MEG.0b013e3283457b09", "ISSN" : "1473-5687", "PMID" : "21399506", "abstract" : "BACKGROUND AND AIM Intractable pain usually dominates the clinical presentation of chronic pancreatitis (CP). Slowing of electroencephalogram (EEG) rhythmicity has been associated with abnormal cortical pain processing in other chronic pain disorders. The aim of this study was to investigate the spectral distribution of EEG rhythmicity in patients with CP. PATIENTS AND METHODS Thirty-one patients with painful CP (mean age 52 years, 19 male) and 15 healthy volunteers (mean age 49, nine male) were included. A multichannel EEG was recorded from 62 surface electrodes. Amplitude strengths of the resting EEG were retrieved based on wavelet frequency analysis and summarized in frequency bands with corresponding topographic mapping. RESULTS Patients with CP had slowed EEG rhythmicity compared with healthy volunteers. This was evident as increased activity in the lower frequency bands \u03b4 (1-3.5 Hz) (P=0.05), \u03b8 (3.5-7.5 Hz) (P<0.001) and \u03b1 (7.5-13.5 Hz) (P<0.001). Due to normalization a reciprocal relationship was observed for the high frequency band \u03b2 (13.5-32 Hz). In a sub-analysis, \u03b4 band activity was modified by diabetes, opioid treatment and alcohol aetiology of CP. However, no effect modification was seen for the \u03b8 or \u03b1 bands. Differences in \u03b8 activity were located over centro-frontal brain regions, whereas differences in \u03b4, \u03b1 and \u03b2 band activity were located in frontal regions. CONCLUSION Slowed EEG rhythmicity was evident in patients with CP. This possibly mirrors abnormal central pain processing and may serve as a clinically useful biomarker of abnormal central pain processing.", "author" : [ { "dropping-particle" : "", "family" : "Olesen", "given" : "S\u00f8ren S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hansen", "given" : "Tine M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graversen", "given" : "Carina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steimle", "given" : "Kristoffer", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "Oliver H G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn Mohr", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European journal of gastroenterology & hepatology", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "2011", "5" ] ] }, "note" : "NULL", "page" : "418-24", "title" : "Slowed EEG rhythmicity in patients with chronic pancreatitis: evidence of abnormal cerebral pain processing?", "type" : "article-journal", "volume" : "23" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1159/000321644", "ISSN" : "1424-3911", "PMID" : "21273802", "abstract" : "BACKGROUND/AIMS In various chronic pain conditions cortical reorganisation seems to play a role in the symptomatology. The aims of this study were to investigate cortical reorganisation in patients with pain caused by chronic pancreatitis (CP) and to correlate putative cortical reorganisation to clinical pain scores. METHODS 24 patients suffering from CP and 14 healthy volunteers were included. Patients' daily experience of pain was recorded in a pain diary. The sigmoid was stimulated electrically with simultaneous recording of evoked brain potentials (EPs). The brain source localisations reflecting direct neuronal activity were fitted by a five-dipole model projected to magnetic resonance imaging of the individual brains. RESULTS Patients showed prolonged latencies of the EPs confined to the frontal region of the brain (p < 0.01). The corresponding brain sources were located in the bilateral insula, cingulate gyrus and bilateral secondary somatosensory area. The insular dipoles were localised more posterior in the patients than in healthy subjects (p < 0.01). The shift in insular dipole localisation was negatively correlated with the patients' clinical pain scores (p < 0.05). CONCLUSIONS The findings indicate that sustained pain in CP leads to functional reorganisation of the insular cortex. We suggest its physiological correlate to be an adaptive response to chronic pain. and IAP.", "author" : [ { "dropping-particle" : "", "family" : "Olesen", "given" : "S\u00f8ren Schou", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fr\u00f8kj\u00e6r", "given" : "Jens Br\u00f8ndum", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lelic", "given" : "Dina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valeriani", "given" : "Massimiliano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn Mohr", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]", "id" : "ITEM-3", "issue" : "6", "issued" : { "date-parts" : [ [ "2010", "3" ] ] }, "note" : "NULL", "page" : "742-51", "title" : "Pain-associated adaptive cortical reorganisation in chronic pancreatitis.", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(39\u201341)", "plainTextFormattedCitation" : "(39\u201341)", "previouslyFormattedCitation" : "(39\u201341)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(39–41). The CNS may also be affected as seen by microstructural changes in cingulate and prefrontal cortices with differences noted in brain imaging between patients with episodic versus continuous pain as well as overall correlations between MRI findings and pain scoresADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/gut.2010.236620", "ISSN" : "1468-3288", "PMID" : "21610272", "abstract" : "OBJECTIVE In patients with painful chronic pancreatitis (CP) there is increasing evidence of abnormal pain processing in the central nervous system. Using magnetic resonance (MR) diffusion tensor imaging, brain microstructure in areas involved in processing of visceral pain was characterised and these findings were correlated to clinical pain scores. METHODS 23 patients with CP pain and 14 controls were studied in a 3T MR scanner. Apparent diffusion coefficient (ADC) (ie, diffusivity of water) and fractional anisotropy (FA) (ie, organisation of fibres) values were assessed in the amygdala, cingulate cortex, insula, prefrontal cortex and secondary sensory cortex. Daily pain scores and the Brief Pain Inventory Short Form were collected 1 week before the investigation. RESULTS In grey matter, patients had increased ADC values in amygdala, cingulate cortex, insula and prefrontal cortex, as well as decreased FA values in cingulate cortex and secondary sensory cortex. In white matter, patients had increased ADC values in insula and prefrontal cortex, and decreased FA values in insula and prefrontal cortex (all p values <0.05). An effect modification from the pain pattern (attacks vs continuous pain) was seen in the insula and secondary sensory cortex (p values <0.05), but no effect modifications from diabetes, alcoholic aetiology and opioid treatment were seen (all p values >0.05). Microstructural changes in cingulate and prefrontal cortices were correlated to patients' clinical pain scores. CONCLUSION The findings suggest that microstructural changes of the brain accompany pain in CP. The changes are likely to be a consequence of ongoing pain and structural reorganisation of the neuromatrix as also seen in other diseases characterised by chronic pain.", "author" : [ { "dropping-particle" : "", "family" : "Fr\u00f8kj\u00e6r", "given" : "Jens Br\u00f8ndum", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olesen", "given" : "S\u00f8ren Schou", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gram", "given" : "Mikkel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yavarian", "given" : "Yousef", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bouwense", "given" : "Stefan A W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "Oliver H G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn Mohr", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gut", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2011", "11", "1" ] ] }, "page" : "1554-62", "title" : "Altered brain microstructure assessed by diffusion tensor imaging in patients with chronic pancreatitis.", "type" : "article-journal", "volume" : "60" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(68)", "plainTextFormattedCitation" : "(68)", "previouslyFormattedCitation" : "(68)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(68). ConclusionsOngoing, comprehensive and multidimensional pain assessment is integral in CP and the factors overviewed here would be appropriate measures to include in such an evaluation. These variables and assessment of the type of pain a CP patient is experiencing (visceral, neuropathic, central, etc. and any overlap) may aid in treatment planning. While an in-depth and thorough QST assessment may not be realistic for everyday clinical use in CP patients, brief, mobile “bedside” assessments are available for classifying patients with other chronic pain conditionsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nrneurol.2013.157", "ISSN" : "1759-4766", "PMID" : "23917848", "author" : [ { "dropping-particle" : "", "family" : "Birklein", "given" : "Frank", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sommer", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature reviews. Neurology", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2013", "9", "6" ] ] }, "note" : "NULL", "page" : "490-2", "title" : "Pain: Quantitative sensory testing--a tool for daily practice?", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.ejpain.2008.01.005", "ISSN" : "10903801", "PMID" : "18325802", "abstract" : "BACKGROUND An appropriate bedside test for small fiber neuropathy does not exist so far. Cold hypaesthesia occurs as an early onset symptom, and the new handheld device NeuroQuick (NQ) was recently claimed to be a valid and reliable screening tool for its quantitative assessment. AIMS Comparison of the NQ with standardized quantitative sensory testing (QST) in patients suffering from chronic painful dysaesthesia with and without pathological cold detection threshold (CDT). METHODS Forty-one patients with and without diabetes mellitus displaying chronic painful dysaesthesia were included (18 men, 55.8+/-13 years). According to the German network protocol QST was performed in the body area with the severest symptoms and at the opposite side as control after thorough clinical-neurological examination. The NeuroQuick, developed as quantitative bedside testing of cold thermal perception based on the wind chill, was used subsequently. RESULTS DT was pathologically increased in 14 and within normal range in 27 patients; NQ values were pathological in 9 and non-pathological in 32 patients. Thus NQ obtained 7.4% false positive and 50% false negative results in detecting cold hypaesthesia, corresponding to 92.6% specificity, 50% sensitivity and a positive and negative predictive value of 78%, respectively. CONCLUSIONS This study demonstrates that the NeuroQuick is not an adequate screening device for cold hypaesthesia in patients with chronic neuropathic pain. It exhibits a high specificity but only low sensitivity in the identification of such small fiber dysfunction; a reliable and valid screening tool should necessarily provide opposite features.", "author" : [ { "dropping-particle" : "", "family" : "Haussleiter", "given" : "Ida S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Richter", "given" : "Helmut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scherens", "given" : "Andrea", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwenkreis", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tegenthoff", "given" : "Martin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maier", "given" : "Christoph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Journal of Pain", "id" : "ITEM-2", "issue" : "8", "issued" : { "date-parts" : [ [ "2008", "11" ] ] }, "note" : "NULL", "page" : "1000-1007", "title" : "NeuroQuick - A novel bedside test for small fiber neuropathy?", "type" : "article-journal", "volume" : "12" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1007/s00296-014-3191-z", "ISSN" : "1437-160X", "PMID" : "25510290", "abstract" : "There are no standardized bedside assessments for subtyping patients with osteoarthritis (OA) based on pain mechanisms. Thus, we developed a bedside sensory testing kit (BSTK) to classify OA patients based on sensory profiles potentially indicative of pain mechanism. After usability and informal reliability testing (n = 22), the kit was tested in a formal reliability study (n = 20). Patients completed questionnaires and sensory testing: pressure algometry to detect hyperalgesia; repeat algometry after heterotopic noxious conditioning stimulation to measure diffuse noxious inhibitory control (DNIC); light touch using Von Frey filaments; and cold allodynia using a brass rod. The procedure was brief and well tolerated. Algometry and filament testing were highly reliable [intra-class correlation coefficients (ICCs) 0.71-0.91]; DNIC was acceptably reliable (ICCs 0.53-0.91); brass rod reliability was inconclusive. Patients were classified empirically into four groups: \"All abnormal findings\" (primary and secondary hyperalgesia and dysfunctional DNIC); \"all normal findings\"; and two intermediate groups. The \"all abnormal findings\" group had more neuropathic pain symptoms, and lower WOMAC total, stiffness, and activity scores than the \"all normal findings\" group. Simple BSTK procedures, consolidated in a kit, reliably classified OA patients into subgroups based on sensory profile, suggesting that OA patients differ in underlying pain mechanisms. Further research is needed to confirm these subgroups and determine their validity in predicting response to treatment.", "author" : [ { "dropping-particle" : "", "family" : "Osgood", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trudeau", "given" : "Jeremiah J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eaton", "given" : "Thomas A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jensen", "given" : "Mark P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gammaitoni", "given" : "Arnold", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Simon", "given" : "Lee S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katz", "given" : "Nathaniel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology international", "id" : "ITEM-3", "issue" : "6", "issued" : { "date-parts" : [ [ "2015", "6", "16" ] ] }, "note" : "NULL", "page" : "1005-13", "title" : "Development of a bedside pain assessment kit for the classification of patients with osteoarthritis.", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(112\u2013114)", "plainTextFormattedCitation" : "(112\u2013114)", "previouslyFormattedCitation" : "(112\u2013114)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(112–114) and may be useful in CP. Such assessment has the potential to aid in a mechanistic approach to personalized treatment and the tracking of tangible outcomes.Eva Szigethy & Pramod Kumar Garg Q4. What is the role of smoking and alcohol on pain treatment in CP Abstinence from alcohol and smoking, in addition to adequate treatment, should be strongly advised in patients with CP (Quality assessment: moderate (alcohol) to weak (smoking); Recommendation: strong; Agreement: strong)Alcohol: Pain is the most common symptom in chronic alcohol- related pancreatitis. While high alcohol intake is a risk factor for pancreatitis, this relationship relative to acute and chronic pancreatitis has recently been established. In a meta-analysis of 7 association studies with 157,026 participants and 3618 cases of pancreatitisADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.ebiom.2015.11.023", "ISSN" : "2352-3964", "PMID" : "26844279", "abstract" : "BACKGROUND Pancreatitis is a highly prevalent medical condition associated with a spectrum of endocrine and exocrine pancreatic insufficiencies. While high alcohol consumption is an established risk factor for pancreatitis, its relationship with specific types of pancreatitis and a potential threshold have not been systematically examined. METHODS We conducted a systematic literature search for studies on the association between alcohol consumption and pancreatitis based on PRISMA guidelines. Non-linear and linear random-effect dose-response meta-analyses using restricted cubic spline meta-regressions and categorical meta-analyses in relation to abstainers were conducted. FINDINGS Seven studies with 157,026 participants and 3618 cases of pancreatitis were included into analyses. The dose-response relationship between average volume of alcohol consumption and risk of pancreatitis was monotonic with no evidence of non-linearity for chronic pancreatitis (CP) for both sexes (p = 0.091) and acute pancreatitis (AP) in men (p = 0.396); it was non-linear for AP in women (p = 0.008). Compared to abstention, there was a significant decrease in risk (RR = 0.76, 95%CI: 0.60-0.97) of AP in women below the threshold of 40 g/day. No such association was found in men (RR = 1.1, 95%CI: 0.69-1.74). The RR for CP at 100 g/day was 6.29 (95%CI: 3.04-13.02). INTERPRETATION The dose-response relationships between alcohol consumption and risk of pancreatitis were monotonic for CP and AP in men, and non-linear for AP in women. Alcohol consumption below 40 g/day was associated with reduced risk of AP in women. Alcohol consumption beyond this level was increasingly detrimental for any type of pancreatitis. FUNDING The work was financially supported by a grant from the National Institute on Alcohol Abuse and Alcoholism (R21AA023521) to the last author.", "author" : [ { "dropping-particle" : "V", "family" : "Samokhvalov", "given" : "Andriy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rehm", "given" : "J\u00fcrgen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roerecke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "EBioMedicine", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2015", "12" ] ] }, "note" : "NULL", "page" : "1996-2002", "title" : "Alcohol Consumption as a Risk Factor for Acute and Chronic Pancreatitis: A Systematic Review and a Series of Meta-analyses.", "type" : "article-journal", "volume" : "2" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(115)", "plainTextFormattedCitation" : "(115)", "previouslyFormattedCitation" : "(115)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(115), the dose-response relationship between average volume of alcohol intake and chronic pancreatitis was monotonic in both men and women and for acute pancreatitis in men. The relationship was highly significant, but non-linear for acute pancreatitis in women. Compared to abstinence, there was a significant reduction of risk of acute pancreatitis in women below a threshold dose of 40g per day, but not for men. Alcohol consumption at a higher daily dose increased the risk of any type of pancreatitis. Recurrence of pancreatitis is high among patients with alcohol related acute pancreatitis. In a study of 562 patients in Finland the recurrence rate was 46% over 1-20 yearsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0036-5521", "PMID" : "10868461", "abstract" : "BACKGROUND Owing to the current lack of long-term follow-up data on the recurrence of alcohol-induced acute pancreatitis (AP), we studied the pattern of recurrence and determined the characteristics of the disease to predict the recurrence. METHODS Between 1972 and 1991, 2678 AP episodes were detected; 1555 were induced by alcohol, and 591 of them were the first episode. During the first alcohol-induced AP 29 patients died and were excluded from further analysis. Of the 562 included, 503 were men, and 59 women. Admission serum tests, severity index, development of complications, intensive care unit and hospital stay, and need for surgery were assessed. Case records were studied. The national database was used to detect admissions to other hospitals. RESULTS Overall, 260 (46%) developed recurrent disease. Of the first relapses, 80% developed during 4 years. The recurrence rate has not changed with time. Age less than 45 years increased the risk (odds ratio (OR) = 2.42; 95% confidence interval (CI), 1.30-4.50). The risk factors of the first alcohol-induced AP associated with the development of multi-recurring pancreatitis are age <45 years (OR, 2.42; 95% CI, 1.59-13.0), 0-2 positive Glasgow criteria (OR, 2.45; 95% CI, 1.16-5.19), and arterial oxygen tension >60 mmHg (OR, 9.90; 95% CI, 1.32-74.3). CONCLUSIONS Fewer than half of the patients develop recurrent alcohol-induced AP. Younger patients are at the highest risk of recurrence. Those whose first alcohol-induced pancreatitis episode was not severe are at a higher risk of developing multi-recurring pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Pelli", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sand", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laippala", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nordback", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of gastroenterology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2000", "5" ] ] }, "note" : "NULL", "page" : "552-5", "title" : "Long-term follow-up after the first episode of acute alcoholic pancreatitis: time course and risk factors for recurrence.", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(116)", "plainTextFormattedCitation" : "(116)", "previouslyFormattedCitation" : "(116)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(116). Similarly, 37–48% recurrence rates have been reported in other studiesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1572-0241.2002.05907.x", "ISSN" : "0002-9270", "PMID" : "12190160", "abstract" : "OBJECTIVE A great number of studies have been published on acute pancreatitis, but few have focused on the recurrent form. In this study, we have sought to determine the relative frequency and mortality of recurrent acute pancreatitis, and also to update our knowledge of its etiological factors. METHODS Patients were selected from a total of 1068 persons included in a previous European study of acute pancreatitis. All were admitted to a hospital with an attack of acute pancreatitis between January, 1990 and December, 1994. Data for each patient was recorded on a standardized form. RESULTS Of the 1068 with acute pancreatitis, 288 (27%) had recurrent pancreatitis; the majority (78.8%) were men, with a mean age of 43 yr (range 16-95 yr). Regarding etiology, alcohol was the most frequent factor (57%), followed by gallstones (25%), other factors (7.6%), and no identified factor (10.4%). Of the 288 patients, 17 (5.9%) died, all of whom had necrotizing pancreatitis; among all of the patients with necrotizing pancreatitis (141 of 288), the mortality was 12.1%. These percentages are lower than those for patients who had a single attack (8.5% and 18.6%, respectively), but not to a statistically significant degree. Mortality was significantly lower among patients with alcoholic pancreatitis (6.9%) than among those with biliary (30%) (p < 0.002) or idiopathic pancreatitis (25%) (p < 0.04). Most of the deaths (82.4%) occurred at the second attack of pancreatitis. CONCLUSION Acute recurrent pancreatitis remains a frequent disease, with alcohol being the most frequent etiological factor. Mortality is similar to that of a single episode of acute pancreatitis, and it is significantly lower among patients with alcohol as the etiology.", "author" : [ { "dropping-particle" : "", "family" : "Gullo", "given" : "Lucio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Migliori", "given" : "Marina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pezzilli", "given" : "Raffaele", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ol\u00e1h", "given" : "Attila", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Farkas", "given" : "Gyula", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Levy", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arvanitakis", "given" : "Constantine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lankisch", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beger", "given" : "Hans", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American journal of gastroenterology", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2002", "8" ] ] }, "note" : "NULL", "page" : "1959-62", "title" : "An update on recurrent acute pancreatitis: data from five European countries.", "type" : "article-journal", "volume" : "97" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1080/00365520510024133", "ISSN" : "0036-5521", "PMID" : "16484129", "abstract" : "OBJECTIVE The aim of this study was to compare long-term recurrence and death rates after a first episode of acute pancreatitis in patients with and without gallstones. Additionally, it was of interest to find out if there were factors predictive of readmission or death. MATERIAL AND METHODS Over a period of 3 years (1995 to 1998), 155 patients admitted with a first attack of acute pancreatitis were included in the study. They followed a specific protocol (ultrasound within 24 h, laboratory tests, Ranson scoring and patients with severe pancreatitis computed tomography scans). In gallstones, pancreatitis, either ERCP or cholecystectomy, was performed at admission or in the case of the latter within 4 weeks. A follow-up was done in January 2002. RESULTS Forty-one percent of the patients without gallstones were readmitted to hospital during the period of follow-up compared to 10% in the group of patients with gallstones. Using multivariate analysis, no factors were significantly predictive of readmission. CONCLUSIONS We found an identical mortality rate of 15% in the two groups, the only predictive factor being age.", "author" : [ { "dropping-particle" : "", "family" : "Lund", "given" : "Helle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "T\u00f8nnesen", "given" : "Hanne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "T\u00f8nnesen", "given" : "Maja Hanne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olsen", "given" : "Ole", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of gastroenterology", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2006", "2", "8" ] ] }, "note" : "NULL", "page" : "234-8", "title" : "Long-term recurrence and death rates after acute pancreatitis.", "type" : "article-journal", "volume" : "41" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(117,118)", "plainTextFormattedCitation" : "(117,118)", "previouslyFormattedCitation" : "(117,118)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(117,118). Prospective studies evaluating the effects of cessation on chronic pain are lacking, but even in the absence of a direct causal relationship with CP-related pain, the health risks of alcohol use, including acceleration of disease progression, still makes abstinence advisable. For treatment of alcohol-related pancreatitis, abstinence from alcohol is associated with reduction in frequency of recurrence of pancreatitis. In a prospective observational study, patients with first attack of alcoholic acute pancreatitis were followed-up for 2 years; out of 51 patients, 13 who remained abstinent at 2 years had no recurrence compared with compared with 17 patients with continued alcohol consumptionADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/00365520701843027", "ISSN" : "0036-5521", "PMID" : "18415757", "abstract" : "OBJECTIVE In an earlier retrospective study we showed that 46% of patients with acute alcoholic pancreatitis had recurrent attacks within 10-20 years, about 30% having a recurrence during the first 3 years. The aim of this prospective follow-up study was to determine the risk factors associated with recurrences. MATERIAL AND METHODS Sixty-eight patients, (59 M, 9 F, mean age 46 years, range 25-71 years) who survived their first acute alcohol-induced pancreatitis from January 2001 to January 2004 volunteered to participate in the study. The diagnostic criteria for acute pancreatitis were epigastric pain, serum amylase > 3 times the upper normal range, elevated serum C-reactive protein (CRP), and signs of acute pancreatitis in imaging. Other etiologies were excluded. Alcohol consumption and dependency were detected by the Alcohol Use Disorders Identification Test (AUDIT) and the Short Alcohol Dependence Data (SADD), respectively, and by attempting to evaluate recent use in grams of pure alcohol. Social and demographic data of the patients, smoking, body mass index, and the severity of the pancreatitis were recorded. Serum and fecal markers of the endocrine and exocrine function and secretin-stimulated MRCP were studied. The patients were followed for a median 38 (25-61) months for recurrences, and at the 2-year time-point had a follow-up visit to investigate any changes in alcohol consumption. RESULTS Seventeen (25%) patients had recurrences of acute alcoholic pancreatitis during the follow-up. Pre-illness alcohol consumption, the severity of the pancreatitis, patient's social or demographic data, pancreatic function tests or morphologic changes in MRCP, or smoking did not correlate with recurrence. None of the 13 patients with consistent total abstinence from alcohol at 2 years developed recurrent pancreatitis compared with 17 out of 51 (33%) patients with at least some alcohol consumption (p = 0.02). Use of other sedatives than alcohol before the first attack of pancreatitis was an independent risk factor associated with recurrence (HR = 6.95, 95% CI 2.45-19.72, p < 0.001). A lower reduction in dependency on alcohol (less decreased SADD points) during 2 years was associated with a higher recurrence rate (HR = 0.921/each reduced point, 95% CI 0.872-0.974, p=0.004). CONCLUSIONS Contrary to chronic pancreatitis, smoking was not found to be a risk factor for recurrent episodes after the first attack of acute alcoholic pancreatitis. Abstinence from alcohol p\u2026", "author" : [ { "dropping-particle" : "", "family" : "Pelli", "given" : "Hanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lappalainen-Lehto", "given" : "Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Piironen", "given" : "Anneli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sand", "given" : "Juhani", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nordback", "given" : "Isto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian Journal of Gastroenterology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2008", "1", "8" ] ] }, "note" : "NULL", "page" : "614-621", "title" : "Risk factors for recurrent acute alcohol-associated pancreatitis: A prospective analysis", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(119)", "plainTextFormattedCitation" : "(119)", "previouslyFormattedCitation" : "(119)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(119). In a randomized controlled trial, 120 with alcohol-associated AP were randomized either to repeated intervention or initial intervention only for alcohol abstinence. Alcohol abstinence in the repeated intervention group resulted in significant reduction in recurrence of pancreatitis (9 vs. 20 episodes)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1053/j.gastro.2008.11.044", "ISSN" : "1528-0012", "PMID" : "19162029", "abstract" : "BACKGROUND & AIMS In the long term, half of patients with their first alcohol-associated acute pancreatitis (AP) develop acute recurrence, alcohol consumption being the main risk factor. None of the recent national or international guidelines for treatment include recommendations aimed to decrease recurrences, possibly because of a lack of studies. This study investigated whether AP recurrences can be reduced. METHODS One hundred and twenty patients admitted to a university hospital for their first alcohol-associated AP were randomized either to repeated intervention (n = 59) or initial intervention only (n = 61). The patients in the 2 groups did not differ. A registered nurse performed an intervention in both groups before discharge, after which it was repeated in the study group at 6-month intervals at the gastrointestinal outpatient clinic. Acute recurrences during the next 2 years were monitored. RESULTS There were 9 recurrent AP episodes in 5 patients in the repeated-intervention group compared with 20 episodes (P = .02) in 13 patients (P = .04) in the control group. The recurrence rates were similar during the first 6 months (4 vs 5 episodes), after which the repeated-intervention group had fewer recurrences than the control group (5 vs 15 episodes; P = .02). CONCLUSIONS The repeated visits at 6-month intervals at the gastrointestinal outpatient clinic, consisting of an intervention against alcohol consumption, appear to be better than the single standardized intervention alone during hospitalization in reducing the development of recurrent AP during a 2-year period.", "author" : [ { "dropping-particle" : "", "family" : "Nordback", "given" : "Isto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pelli", "given" : "Hanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lappalainen-Lehto", "given" : "Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "J\u00e4rvinen", "given" : "Satu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "R\u00e4ty", "given" : "Sari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sand", "given" : "Juhani", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2009", "3" ] ] }, "note" : "NULL", "page" : "848-55", "title" : "The recurrence of acute alcohol-associated pancreatitis can be reduced: a randomized controlled trial.", "type" : "article-journal", "volume" : "136" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(120)", "plainTextFormattedCitation" : "(120)", "previouslyFormattedCitation" : "(120)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(120). The authors followed up these patients to study the long-term outcome of patients who abstained. Of the 118 patients, 18 who remained abstinent had no further attack of pancreatitis during a mean follow-up of mean 5 years, compared to 34% of the 100 non-abstinent patients who had at least one recurrence during the follow-upADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/alcalc/agt019", "ISSN" : "1464-3502", "PMID" : "23538610", "abstract" : "AIMS To determine the recurrence of pancreatitis and subsequent pancreatic function in patients who stop drinking after the first episode of alcohol-associated pancreatitis. METHODS Of a total of 118 patients suffering from their first alcohol-associated pancreatitis, 18 (all men, age median 47 (27-71) years) met the inclusion criterion for abstinence during follow-up. The criterion for abstinence was alcohol consumption <24 g per 2 months (self-estimated), which is in line with questionnaires eliciting alcohol consumption and dependency (Alcohol Use Disorders Identification Test < 8 and Short Alcohol Dependence Data < 9). Recurrent attacks of acute pancreatitis were studied. Smoking, body mass index and laboratory tests detecting heavy consumption of alcohol were recorded. Blood and faecal tests were studied to assess endocrine and exocrine pancreatic function. RESULTS During a mean follow-up time of 5.15 (1.83-9.13) years and a total of 92.7 patient-years, there were no recurrent attacks of acute pancreatitis among the 18 abstainers. Two patients had diabetes prior to and one was diagnosed immediately after the first episode of acute pancreatitis. One patient had impaired glucose metabolism at 2 years. Two patients had low insulin secretion in glucagon-C-peptide test, one at 4 years and the other at 5 years. Only one patient (6%) maintained low elastase-1 activity during the abstinence follow-up. Of the 100 non-abstainers, 34% had at least one recurrence during the follow-up. CONCLUSION Regardless of the mediator mechanisms of acute alcoholic pancreatitis, abstinence after the first episode protects against recurrent attacks. Pancreatic dysfunction is also rare among abstinent patients.", "author" : [ { "dropping-particle" : "", "family" : "Nikkola", "given" : "Jussi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "R\u00e4ty", "given" : "Sari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laukkarinen", "given" : "Johanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sepp\u00e4nen", "given" : "Hanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lappalainen-Lehto", "given" : "Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "J\u00e4rvinen", "given" : "Satu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nordback", "given" : "Isto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sand", "given" : "Juhani", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Alcohol and alcoholism (Oxford, Oxfordshire)", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2013", "7", "1" ] ] }, "note" : "NULL", "page" : "483-6", "title" : "Abstinence after first acute alcohol-associated pancreatitis protects against recurrent pancreatitis and minimizes the risk of pancreatic dysfunction.", "type" : "article-journal", "volume" : "48" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(121)", "plainTextFormattedCitation" : "(121)", "previouslyFormattedCitation" : "(121)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(121). Pharmacological treatment is often necessary to ensure that the patients refrain from alcohol intake. Benzodiazepines remain the gold standard to reduce symptoms of alcohol withdrawal including seizures and delirium tremensADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s40265-015-0358-1", "ISSN" : "1179-1950", "PMID" : "25666543", "abstract" : "Symptoms of alcohol withdrawal syndrome (AWS) may develop within 6-24\u00a0h after the abrupt discontinuation or decrease of alcohol consumption. Symptoms can vary from autonomic hyperactivity and agitation to delirium tremens. The gold-standard treatment for AWS is with benzodiazepines (BZDs). Among the BZDs, different agents (i.e., long-acting or short-acting) and different regimens (front-loading, fixed-dose or symptom-triggered) may be chosen on the basis of patient characteristics. Severe withdrawal could require ICU admission and the use of barbiturates or propofol. Other drugs, such as \u03b12-agonists (clonidine and dexmetedomidine) and \u03b2-blockers can be used as adjunctive treatments to control neuroautonomic hyperactivity. Furthermore, neuroleptic agents can help control hallucinations. Finally, other medications for the treatment for AWS have been investigated with promising results. These include carbamazepine, valproate, sodium oxybate, baclofen, gabapentin and topiramate. The usefulness of these agents are discussed.", "author" : [ { "dropping-particle" : "", "family" : "Mirijello", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "D'Angelo", "given" : "Cristina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferrulli", "given" : "Anna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vassallo", "given" : "Gabriele", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Antonelli", "given" : "Mariangela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caputo", "given" : "Fabio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leggio", "given" : "Lorenzo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gasbarrini", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Addolorato", "given" : "Giovanni", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Drugs", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2015", "3", "10" ] ] }, "note" : "NULL", "page" : "353-65", "title" : "Identification and management of alcohol withdrawal syndrome.", "type" : "article-journal", "volume" : "75" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1111/j.1365-2710.2009.01098.x", "ISSN" : "1365-2710", "PMID" : "20456734", "abstract" : "OBJECTIVE The goal of this review is to evaluate the efficacy and safety of carbamazepine and oxcarbazepine in treatment of alcohol withdrawal syndrome (AWS) and determine the role in therapy of both agents. METHODS Relevant literature was identified through a search of MEDLINE (1966-June 2008), PubMed (1966-June 2008); Cochrane database was performed to identify English-language publications. Search terms included carbamazepine, oxcarbazepine, AWS, alcoholism, substance syndrome withdrawal. RESULTS In seven studies, including 612 patients, carbamazepine demonstrated significant reduction in alcohol withdrawal scores. However, in comparative trials with a benzodiazepine agent, carbamazepine's ability to prevent alcohol withdrawal seizures (OR = 0.93; 95% CI = 0.06-14.97, P = NS) and delirium tremens (DTs; OR = 1.25; 95% CI = 0.28-5.64, P = NS) was uncertain as a result of insufficient patient enrollment. In three trials, carbamazepine failed to reduce alcohol withdrawal symptoms possibly as a result of delayed administration, inadequate dosage or inadequate sample size. At daily doses of 800 mg either fixed or tapered over 5-9 days, carbamazepine was well tolerated, and safely administered when blood alcohol concentration dropped below 0.15%. The role of oxcarbazepine in AWS is undefined because of inconsistent findings in two trials. CONCLUSION Carbamazepine has demonstrated safety, tolerability and efficacy in treatment of moderate to severe symptoms of alcohol withdrawal in the inpatient setting. However, trials of carbamazepine provide inconclusive evidence for prevention of alcohol withdrawal seizures and DTs in comparison with benzodiazepines. Benzodiazepines remain the primary treatment of moderate to severe AWS.", "author" : [ { "dropping-particle" : "", "family" : "Barrons", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roberts", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of clinical pharmacy and therapeutics", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2010", "4" ] ] }, "note" : "NULL", "page" : "153-67", "title" : "The role of carbamazepine and oxcarbazepine in alcohol withdrawal syndrome.", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(122,123)", "plainTextFormattedCitation" : "(122,123)", "previouslyFormattedCitation" : "(122,123)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(122,123). Long-term use of benzodiazepines carry the risk of abuse, addiction and liver toxicity. Mood stabilizers such as carbamazepine are safe and efficacious in treating moderate symptoms of alcohol withdrawalADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1365-2710.2009.01098.x", "ISSN" : "1365-2710", "PMID" : "20456734", "abstract" : "OBJECTIVE The goal of this review is to evaluate the efficacy and safety of carbamazepine and oxcarbazepine in treatment of alcohol withdrawal syndrome (AWS) and determine the role in therapy of both agents. METHODS Relevant literature was identified through a search of MEDLINE (1966-June 2008), PubMed (1966-June 2008); Cochrane database was performed to identify English-language publications. Search terms included carbamazepine, oxcarbazepine, AWS, alcoholism, substance syndrome withdrawal. RESULTS In seven studies, including 612 patients, carbamazepine demonstrated significant reduction in alcohol withdrawal scores. However, in comparative trials with a benzodiazepine agent, carbamazepine's ability to prevent alcohol withdrawal seizures (OR = 0.93; 95% CI = 0.06-14.97, P = NS) and delirium tremens (DTs; OR = 1.25; 95% CI = 0.28-5.64, P = NS) was uncertain as a result of insufficient patient enrollment. In three trials, carbamazepine failed to reduce alcohol withdrawal symptoms possibly as a result of delayed administration, inadequate dosage or inadequate sample size. At daily doses of 800 mg either fixed or tapered over 5-9 days, carbamazepine was well tolerated, and safely administered when blood alcohol concentration dropped below 0.15%. The role of oxcarbazepine in AWS is undefined because of inconsistent findings in two trials. CONCLUSION Carbamazepine has demonstrated safety, tolerability and efficacy in treatment of moderate to severe symptoms of alcohol withdrawal in the inpatient setting. However, trials of carbamazepine provide inconclusive evidence for prevention of alcohol withdrawal seizures and DTs in comparison with benzodiazepines. Benzodiazepines remain the primary treatment of moderate to severe AWS.", "author" : [ { "dropping-particle" : "", "family" : "Barrons", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roberts", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of clinical pharmacy and therapeutics", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2010", "4" ] ] }, "note" : "NULL", "page" : "153-67", "title" : "The role of carbamazepine and oxcarbazepine in alcohol withdrawal syndrome.", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/14651858.CD005064.pub3", "ISSN" : "1469-493X", "PMID" : "20238337", "abstract" : "BACKGROUND Alcohol abuse and dependence represents a most serious health problem worldwide with major social, interpersonal and legal interpolations. Besides benzodiazepines, anticonvulsants are often used for the treatment of alcohol withdrawal symptoms. Anticonvulsants drugs are indicated for the treatment of alcohol withdrawal syndrome, alone or in combination with benzodiazepine treatments. In spite of the wide use, the exact role of the anticonvulsants for the treatment of alcohol withdrawal has not yet bee adequately assessed. OBJECTIVES To evaluate the effectiveness and safety of anticonvulsants in the treatment of alcohol withdrawal. SEARCH STRATEGY We searched Cochrane Drugs and Alcohol Group' Register of Trials (December 2009), PubMed, EMBASE, CINAHL (1966 to December 2009), EconLIT (1969 to December 2009). Parallel searches on web sites of health technology assessment and related agencies, and their databases. SELECTION CRITERIA Randomized controlled trials (RCTs) examining the effectiveness, safety and overall risk-benefit of anticonvulsants in comparison with a placebo or other pharmacological treatment. All patients were included regardless of age, gender, nationality, and outpatient or inpatient therapy. DATA COLLECTION AND ANALYSIS Two authors independently screened and extracted data from studies. MAIN RESULTS Fifty-six studies, with a total of 4076 participants, met the inclusion criteria. Comparing anticonvulsants with placebo, no statistically significant differences for the six outcomes paring anticonvulsant versus other drug, 19 outcomes considered, results favour anticonvulsants only in the comparison carbamazepine versus benzodiazepine (oxazepam and lorazepam) for alcohol withdrawal symptoms (CIWA-Ar score): 3 studies, 262 participants, MD -1.04 (-1.89 to -0.20), none of the other comparisons reached statistical paring different anticonvulsants no statistically significant differences in the two outcomes paring anticonvulsants plus other drugs versus other drugs (3 outcomes considered), results from one study, 72 participants, favour paraldehyde plus chloral hydrate versus chlordiazepoxide, for the severe-life threatening side effects, RR 0.12 (0.03 to 0.44). AUTHORS' CONCLUSIONS Results of this review do not provide sufficient evidence in favour of anticonvulsants for the treatment of AWS. There are some suggestions that carbamazepine may actually be more effective in treating some asp\u2026", "author" : [ { "dropping-particle" : "", "family" : "Minozzi", "given" : "Silvia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Amato", "given" : "Laura", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vecchi", "given" : "Simona", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davoli", "given" : "Marina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cochrane Database of Systematic Reviews", "editor" : [ { "dropping-particle" : "", "family" : "Minozzi", "given" : "Silvia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2010", "3", "17" ] ] }, "note" : "NULL", "page" : "CD005064", "publisher" : "John Wiley & Sons, Ltd", "publisher-place" : "Chichester, UK", "title" : "Anticonvulsants for alcohol withdrawal", "type" : "chapter" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(123,124)", "plainTextFormattedCitation" : "(123,124)", "previouslyFormattedCitation" : "(123,124)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(123,124). It is important that severe withdrawal be treated in a hospital setting or facility where 24-hour monitoring is available for delirium tremens or seizures. Only three medications have FDA-approval to treat alcohol dependence; naltrexone, acamprosate and disulfiram. Naltrexone has strong support in reducing relapse in alcoholicsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0003-990X", "PMID" : "1345133", "abstract" : "Seventy male alcohol-dependent patients participated in a 12-week, double-blind, placebo-controlled trial of naltrexone hydrochloride (50 mg/d) as an adjunct to treatment following alcohol detoxification. Subjects taking naltrexone reported significantly less alcohol craving and days in which any alcohol was consumed. During the 12-week study, only 23% of the naltrexone-treated subjects met the criteria for a relapse, whereas 54.3% of the placebo-treated subjects relapsed. The primary effect of naltrexone was seen in patients who drank any alcohol while attending outpatient treatment. Nineteen (95%) of the 20 placebo-treated patients relapsed after they sampled alcohol, while only eight (50%) of 16 naltrexone-treated patients exposed to alcohol met relapse criteria. Naltrexone was not associated with mood changes or other psychiatric symptoms. Significant side effects (nausea) occurred in two naltrexone-treated subjects, and one naltrexone-treated subject complained of increased pain from arthritis. These results suggest that naltrexone may be a safe and effective adjunct to treatment in alcohol-dependent subjects, particularly in preventing alcohol relapse.", "author" : [ { "dropping-particle" : "", "family" : "Volpicelli", "given" : "J R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alterman", "given" : "A I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayashida", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Brien", "given" : "C P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Archives of general psychiatry", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "1992", "11" ] ] }, "note" : "NULL", "page" : "876-80", "title" : "Naltrexone in the treatment of alcohol dependence.", "type" : "article-journal", "volume" : "49" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(125)", "plainTextFormattedCitation" : "(125)", "previouslyFormattedCitation" : "(125)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(125), while acamprosate has shown efficacy in someADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1001/jama.2014.3628", "ISSN" : "0098-7484", "PMID" : "24825644", "abstract" : "IMPORTANCE: Alcohol use disorders cause substantial morbidity and early mortality yet remain greatly undertreated. Medications are considerably underused.\\n\\nOBJECTIVE: To conduct a systematic review and meta-analysis of the benefits and harms of medications (US FDA-approved and others) for adults with alcohol use disorders.\\n\\nDATA SOURCES: PubMed, Cochrane Library, PsycINFO, CINAHL, EMBASE, FDA website, and clinical trials registries (January 1, 1970, to March 1, 2014).\\n\\nSTUDY SELECTION: Two reviewers selected randomized clinical trials (RCTs) with at least 12 weeks' duration that reported eligible outcomes and head-to-head prospective cohort studies reporting health outcomes or harms.\\n\\nD 1/Downloads/Ferri_et_al-2006-The_Cochrane_Library.pdfATA EXTRACTION AND SYNTHESIS: We conducted meta-analyses using random-effects models and calculated numbers needed to treat for benefit (NNTs) or harm (NNHs).\\n\\nMAIN OUTCOMES AND MEASURES: Alcohol consumption, motor vehicle crashes, injuries, quality of life, function, mortality, and harms.\\n\\nRESULTS: We included 122 RCTs and 1 cohort study (total 22,803 participants). Most assessed acamprosate (27 studies, n = 7519), naltrexone (53 studies, n = 9140), or both. The NNT to prevent return to any drinking for acamprosate was 12 (95% CI, 8 to 26; risk difference [RD], -0.09; 95% CI, -0.14 to -0.04) and was 20 (95% CI, 11 to 500; RD, -0.05; 95% CI, -0.10 to -0.002) for oral naltrexone (50 mg/d). The NNT to prevent return to heavy drinking was 12 (95% CI, 8 to 26; RD -0.09; 95% CI, -0.13 to -0.04) for oral naltrexone (50 mg/d). Meta-analyses of trials comparing acamprosate to naltrexone found no statistically significant difference between them for return to any drinking (RD, 0.02; 95% CI, -0.03 to 0.08) or heavy drinking (RD, 0.01; 95% CI, -0.05 to 0.06). For injectable naltrexone, meta-analyses found no association with return to any drinking (RD, -0.04; 95% CI, -0.10 to 0.03) or heavy drinking (RD, -0.01; 95% CI, -0.14 to 0.13) but found an association with reduction in heavy drinking days (weighted mean difference [WMD], -4.6%; 95% CI, -8.5% to -0.56%). Among medications used off-label, moderate evidence supports an association with improvement in some consumption outcomes for nalmefene (heavy drinking days per month: WMD, -2.0; 95% CI, -3.0 to -1.0; drinks per drinking day: WMD, -1.02; 95% CI, -1.77 to -0.28) and topiramate (% heavy drinking days: WMD, -9.0%; 95% CI, -15.3% to -2.7%; drinks p\u2026", "author" : [ { "dropping-particle" : "", "family" : "Jonas", "given" : "Daniel E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Amick", "given" : "Halle R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Feltner", "given" : "Cynthia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bobashev", "given" : "Georgiy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thomas", "given" : "Kathleen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wines", "given" : "Roberta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Mimi M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shanahan", "given" : "Ellen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gass", "given" : "C. 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It is unknown how combining these treatments may impact their effectiveness, especially in the context of primary care and other nonspecialty settings. OBJECTIVES To evaluate the efficacy of medication, behavioral therapies, and their combinations for treatment of alcohol dependence and to evaluate placebo effect on overall outcome. DESIGN, SETTING, AND PARTICIPANTS Randomized controlled trial conducted January 2001-January 2004 among 1383 recently alcohol-abstinent volunteers (median age, 44 years) from 11 US academic sites with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnoses of primary alcohol dependence. INTERVENTIONS Eight groups of patients received medical management with 16 weeks of naltrexone (100 mg/d) or acamprosate (3 g/d), both, and/or both placebos, with or without a combined behavioral intervention (CBI). A ninth group received CBI only (no pills). Patients were also evaluated for up to 1 year after treatment. MAIN OUTCOME MEASURES Percent days abstinent from alcohol and time to first heavy drinking day. RESULTS All groups showed substantial reduction in drinking. During treatment, patients receiving naltrexone plus medical management (n = 302), CBI plus medical management and placebos (n = 305), or both naltrexone and CBI plus medical management (n = 309) had higher percent days abstinent (80.6, 79.2, and 77.1, respectively) than the 75.1 in those receiving placebos and medical management only (n = 305), a significant naltrexone x behavioral intervention interaction (P = .009). Naltrexone also reduced risk of a heavy drinking day (hazard ratio, 0.72; 97.5% CI, 0.53-0.98; P = .02) over time, most evident in those receiving medical management but not CBI. Acamprosate showed no significant effect on drinking vs placebo, either by itself or with any combination of naltrexone, CBI, or both. During treatment, those receiving CBI without pills or medical management (n = 157) had lower percent days abstinent (66.6) than those receiving placebo plus medical management alone (n = 153) or placebo plus medical management and CBI (n = 156) (73.8 and 79.8, respectively; P<.001). One year after treatment, these between-group effects were similar but no longer significant. CONCLUSIONS Patients receiving medical management with naltrexone, CBI, or both fared better on drinking outcomes, whereas acamprosate showed no evidence of eff\u2026", "author" : [ { "dropping-particle" : "", "family" : "Anton", "given" : "Raymond F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Malley", "given" : "Stephanie S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ciraulo", "given" : "Domenic A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cisler", "given" : "Ron A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Couper", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Donovan", "given" : "Dennis M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gastfriend", "given" : "David R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hosking", "given" : "James D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Bankole A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "LoCastro", "given" : "Joseph S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Longabaugh", "given" : "Richard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mason", "given" : "Barbara J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mattson", "given" : "Margaret E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miller", "given" : "William R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pettinati", "given" : "Helen M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Randall", "given" : "Carrie L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Swift", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weiss", "given" : "Roger D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Williams", "given" : "Lauren D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zweben", "given" : "Allen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "COMBINE Study Research Group", "given" : "for the", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "JAMA", "id" : "ITEM-1", "issue" : "17", "issued" : { "date-parts" : [ [ "2006", "5", "3" ] ] }, "note" : "NULL", "page" : "2003-17", "title" : "Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial.", "type" : "article-journal", "volume" : "295" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(127)", "plainTextFormattedCitation" : "(127)", "previouslyFormattedCitation" : "(127)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(127). More recent research has found that functional genetic polymorphisms may predict who does and does not respond to treatment such as naltrexone for alcohol dependenceADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1001/archpsyc.65.2.135", "ISSN" : "1538-3636", "PMID" : "18250251", "abstract" : "CONTEXT Naltrexone hydrochloride treatment for alcohol dependence works for some individuals but not for everyone. Asn40Asp, a functional polymorphism of the mu-opioid receptor gene (OPRM1), might predict naltrexone response. OBJECTIVE To evaluate whether individuals with alcoholism who are heterozygous (Asp40/Asn40) or homozygous (Asp40/Asp40) for the OPRM1 Asp40 allele respond better to naltrexone. DESIGN Pharmacogenetic analysis conducted between January 1, 2001, and January 31, 2004. SETTING Eleven academic sites in the COMBINE Study. PARTICIPANTS Recently abstinent volunteers who met all 3 of the following conditions: (1) DSM-IV criteria for primary alcohol dependence; (2) participation in the COMBINE Study; and (3) availability of DNA. INTERVENTIONS Alcoholic subjects were treated for 16 weeks with 100 mg of naltrexone hydrochloride (234 Asn40 homozygotes and 67 with at least 1 copy of the Asp40 allele) or placebo (235 Asn40 homozygotes and 68 with at least 1 copy of the Asp40 allele). All participants received medical management (MM) alone or with combined behavioral intervention (CBI). MAIN OUTCOME MEASURES Time trends in percentage of days abstinent, percentage of heavy drinking days, and rates of good clinical outcome. RESULTS Alcoholic subjects with an Asp40 allele receiving MM alone (no CBI) had an increased percentage of days abstinent (P = .07) and a decreased percentage of heavy drinking days (P = .04) if treated with naltrexone vs placebo, while those with the Asn40/Asn40 genotype showed no medication differences. If treated with MM alone and naltrexone, 87.1% of Asp40 carriers had a good clinical outcome, compared with only 54.8% of individuals with the Asn40/Asn40 genotype (odds ratio, 5.75; confidence interval, 1.88-17.54), while, if treated with placebo, 48.6% of Asp40 carriers and 54.0% of individuals with the Asn40/Asn40 genotype had a good clinical outcome (interaction between medication and genotype, P = .005). No gene x medication interactions were observed in those treated with both MM and CBI. CONCLUSIONS These results confirm and extend the observation that the functionally significant OPRM1 Asp40 allele predicts naltrexone treatment response in alcoholic individuals. This relationship might be obscured, however, by other efficacious treatments. OPRM1 genotyping in alcoholic individuals might be useful to assist in selecting treatment options. TRIAL REGISTRATION Identifier: NCT00006206.", "author" : [ { "dropping-particle" : "", "family" : "Anton", "given" : "Raymond F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oroszi", "given" : "Gabor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Malley", "given" : "Stephanie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Couper", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Swift", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pettinati", "given" : "Helen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goldman", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Archives of general psychiatry", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2008", "2", "1" ] ] }, "note" : "NULL", "page" : "135-44", "title" : "An evaluation of mu-opioid receptor (OPRM1) as a predictor of naltrexone response in the treatment of alcohol dependence: results from the Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) study.", "type" : "article-journal", "volume" : "65" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(128)", "plainTextFormattedCitation" : "(128)", "previouslyFormattedCitation" : "(128)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(128). One large-scale study evaluated the efficacy of pharmacological (naltrexone versus acamprosate versus both and/or placebos in combination with medical management with or without behavioral therapy for alcohol dependenceADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.15288/jsad.2008.69.5", "ISSN" : "1937-1888", "author" : [ { "dropping-particle" : "", "family" : "Donovan", "given" : "Dennis M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anton", "given" : "Raymond F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miller", "given" : "William R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Longabaugh", "given" : "Richard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hosking", "given" : "James D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "youngblood", "given" : "Marston", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Studies on Alcohol and Drugs", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2008", "1" ] ] }, "note" : "NULL", "page" : "5-13", "title" : "Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (The COMBINE Study): Examination of Posttreatment Drinking Outcomes", "type" : "article-journal", "volume" : "69" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1001/jama.295.17.2003", "ISSN" : "1538-3598", "PMID" : "16670409", "abstract" : "CONTEXT Alcohol dependence treatment may include medications, behavioral therapies, or both. It is unknown how combining these treatments may impact their effectiveness, especially in the context of primary care and other nonspecialty settings. OBJECTIVES To evaluate the efficacy of medication, behavioral therapies, and their combinations for treatment of alcohol dependence and to evaluate placebo effect on overall outcome. DESIGN, SETTING, AND PARTICIPANTS Randomized controlled trial conducted January 2001-January 2004 among 1383 recently alcohol-abstinent volunteers (median age, 44 years) from 11 US academic sites with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnoses of primary alcohol dependence. INTERVENTIONS Eight groups of patients received medical management with 16 weeks of naltrexone (100 mg/d) or acamprosate (3 g/d), both, and/or both placebos, with or without a combined behavioral intervention (CBI). A ninth group received CBI only (no pills). Patients were also evaluated for up to 1 year after treatment. MAIN OUTCOME MEASURES Percent days abstinent from alcohol and time to first heavy drinking day. RESULTS All groups showed substantial reduction in drinking. During treatment, patients receiving naltrexone plus medical management (n = 302), CBI plus medical management and placebos (n = 305), or both naltrexone and CBI plus medical management (n = 309) had higher percent days abstinent (80.6, 79.2, and 77.1, respectively) than the 75.1 in those receiving placebos and medical management only (n = 305), a significant naltrexone x behavioral intervention interaction (P = .009). Naltrexone also reduced risk of a heavy drinking day (hazard ratio, 0.72; 97.5% CI, 0.53-0.98; P = .02) over time, most evident in those receiving medical management but not CBI. Acamprosate showed no significant effect on drinking vs placebo, either by itself or with any combination of naltrexone, CBI, or both. During treatment, those receiving CBI without pills or medical management (n = 157) had lower percent days abstinent (66.6) than those receiving placebo plus medical management alone (n = 153) or placebo plus medical management and CBI (n = 156) (73.8 and 79.8, respectively; P<.001). One year after treatment, these between-group effects were similar but no longer significant. CONCLUSIONS Patients receiving medical management with naltrexone, CBI, or both fared better on drinking outcomes, whereas acamprosate showed no evidence of eff\u2026", "author" : [ { "dropping-particle" : "", "family" : "Anton", "given" : "Raymond F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Malley", "given" : "Stephanie S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ciraulo", "given" : "Domenic A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cisler", "given" : "Ron A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Couper", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Donovan", "given" : "Dennis M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gastfriend", "given" : "David R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hosking", "given" : "James D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Bankole A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "LoCastro", "given" : "Joseph S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Longabaugh", "given" : "Richard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mason", "given" : "Barbara J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mattson", "given" : "Margaret E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miller", "given" : "William R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pettinati", "given" : "Helen M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Randall", "given" : "Carrie L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Swift", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weiss", "given" : "Roger D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Williams", "given" : "Lauren D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zweben", "given" : "Allen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "COMBINE Study Research Group", "given" : "for the", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "JAMA", "id" : "ITEM-2", "issue" : "17", "issued" : { "date-parts" : [ [ "2006", "5", "3" ] ] }, "note" : "NULL", "page" : "2003-17", "title" : "Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial.", "type" : "article-journal", "volume" : "295" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(127,129)", "plainTextFormattedCitation" : "(127,129)", "previouslyFormattedCitation" : "(127,129)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(127,129). Previous medical management of alcohol dependence and either behavioral therapy, naltrexone, or both was associated with significantly higher reduction of drinking and abstinence evaluated over 68 weeks. No combination had better efficacy in reducing drinking than naltrexone or behavioral therapy alone in the presence of medical management. No significant effects were found with acamprosate. Placebo pills had a positive effect in this study above that of behavioral therapy alone. While disulfiram has been widely used, there is no clear clinical trial data supporting positive outcomesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1055/s-0042-103592", "ISSN" : "1439-0795", "PMID" : "26987743", "abstract" : "As an alcohol-aversive agent, disulfiram occupies an exceptional position in the pharmacological relapse prevention of alcohol dependence. In contrast to anti-craving drugs, disulfiram does not modulate neurobiological mechanisms of addiction, but rather works by producing an aversive reaction when combined with alcohol. Therapeutic and adverse effects are therefore closely related: On the one hand, the aversiveness of the disulfiram ethanol reaction has the potential to support abstinence in a subgroup of alcohol-dependent patients, while on the other hand it becomes a health threat if the patient fails to maintain complete abstinence. The exceptional position of disulfiram is also related to the role that expectations play in the mediation of therapeutic effects. These are not determined by the pharmacological effects or the actual occurrence of a disulfiram-ethanol reaction, but are attributable to patient awareness that the drug was consumed and the corresponding anticipation of an aversive reaction if combined with alcohol. This is in line with the findings of a recent meta-analysis that only showed significant effects for disulfiram in open-label trials. The authors of the meta-analysis conclude that due to expectations induced in both the treatment and placebo groups, blinded studies are incapable of distinguishing a difference between groups. The mediation of therapeutic effects through expectation has a number of consequences for clinical practice and future research on disulfiram.", "author" : [ { "dropping-particle" : "", "family" : "Mutschler", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grosshans", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Soyka", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "R\u00f6sner", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pharmacopsychiatry", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2016", "7", "17" ] ] }, "note" : "NULL", "page" : "137-41", "title" : "Current Findings and Mechanisms of Action of Disulfiram in the Treatment of Alcohol Dependence.", "type" : "article-journal", "volume" : "49" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(130)", "plainTextFormattedCitation" : "(130)", "previouslyFormattedCitation" : "(130)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(130). Other classes of psychotropic medications have been investigated but results are inconclusiveADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/08897077.2015.1133472", "ISSN" : "1547-0164", "PMID" : "26928397", "abstract" : "Alcohol use disorder (AUD), as currently defined in the Diagnostic and Statistical Manual, 5th Edition (DSM-5), is a heterogeneous disorder stemming from a complex interaction of neurobiological, genetic, and environmental factors. As a result of this heterogeneity, there is no one treatment for AUD that will work for everyone. During the past 2 decades, efforts have been made to develop a menu of medications to give patients and clinicians more choices when seeking a therapy that is both effective and which has limited side effects. To date, 3 medications have been approved by the US Food and Drug Administration (FDA) to treat alcohol dependence: disulfiram, naltrexone, and acamprosate. In addition to these approved medications, researchers have identified new therapeutic targets and, as a result, a number of alternative medications are now being evaluated for treatment of AUD in human studies. Although not approved by the FDA for the treatment of AUD, in some cases, these alternative medications are being used off-label by clinicians for this purpose. These potential medications are reviewed here. They include nalmefene, varenicline, gabapentin, topiramate, zonisamide, baclofen, ondansetron, levetiracetam, quetiapine, aripiprazole, and serotonin reuptake inhibitors. The effectiveness of these medications has been mixed-some show good efficacy with side effects that are mild to moderate in intensity; others have mixed or promising results but are awaiting findings from ongoing studies; and still others show poor efficacy, despite promising preliminary results. Medications development remains a high priority. Key initiatives for the National Institute on Alcohol Abuse and Alcoholism (NIAAA) include supporting the discovery and development of more effective and safer medications, advancing the field of personalized medicine, and forging public and private partnerships to investigate new and more effective compounds.", "author" : [ { "dropping-particle" : "", "family" : "Litten", "given" : "Raye Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilford", "given" : "Bonnie B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Falk", "given" : "Daniel E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ryan", "given" : "Megan L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fertig", "given" : "Joanne B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Substance abuse", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2016", "4", "2" ] ] }, "note" : "NULL", "page" : "286-98", "title" : "Potential medications for the treatment of alcohol use disorder: An evaluation of clinical efficacy and safety.", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(131)", "plainTextFormattedCitation" : "(131)", "previouslyFormattedCitation" : "(131)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(131). Limited data on use of selective serotonergic medications showed these may help with treating comorbid psychiatric conditions such as mood and anxiety disorders but not alcohol dependence directly. The identification and treatment of frequent psychiatric comorbidities associated with alcohol dependence is criticalADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1535-7414", "PMID" : "10890809", "abstract" : "Psychiatric disorders occur more often among alcoholics than among the general population. The psychiatric disorders that alcoholics most frequently experience include mood disorders (e.g., depression), anxiety disorders, and antisocial personality disorder. The evaluation of psychiatric symptoms in alcoholic patients is complicated by the multiple relationships that exist among heavy drinking, psychiatric symptoms, and personality factors. For example, alcoholics with co-occurring depression may be at greater risk of psychosocial problems, relapse, and suicide. Conversely, heavy drinking may produce or worsen symptoms of depression or anxiety. Although clinical experience provides general guidance for treating these patients, further research is needed to develop effective psychosocial and pharmacological therapies aimed at specific combinations of psychiatric and addictive disorders.", "author" : [ { "dropping-particle" : "", "family" : "Modesto-Lowe", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kranzler", "given" : "H R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Alcohol research & health : the journal of the National Institute on Alcohol Abuse and Alcoholism", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "1999" ] ] }, "note" : "NULL", "page" : "144-9", "title" : "Diagnosis and treatment of alcohol-dependent patients with comorbid psychiatric disorders.", "type" : "article-journal", "volume" : "23" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "1055-0496", "PMID" : "14972778", "abstract" : "Although alcohol use disorders are commonly associated with co-morbid drug use and psychiatric disorders, such co-morbidity is frequently underdiagnosed and inadequately treated. This paper reviews the epidemiological, diagnostic, and treatment literature on the co-morbidity of alcoholism, with a focus on the most common co-morbid disorders: drug abuse, mood disorders, anxiety disorders, and antisocial personality disorder. The paper goes on to describe a number of promising approaches to the treatment of these common co-morbid disorders in alcoholics. Despite the difficulties inherent in treating dual diagnosis patients, the clinician must recognize that it is possible to derive valid diagnoses and deliver efficacious treatment to such patients.", "author" : [ { "dropping-particle" : "", "family" : "Kranzler", "given" : "Henry R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rosenthal", "given" : "Richard N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American journal on addictions", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2003" ] ] }, "note" : "NULL", "page" : "S26-40", "title" : "Dual diagnosis: alcoholism and co-morbid psychiatric disorders.", "type" : "article-journal", "volume" : "12 Suppl 1" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(132,133)", "plainTextFormattedCitation" : "(132,133)", "previouslyFormattedCitation" : "(132,133)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(132,133). Treatment-na?ve active alcoholics had a greater number of psychiatric symptoms than normal controls, but less than treated alcoholics with long-term abstinence and highlights the importance of identifying subsyndromal psychopathology even when alcohol dependence has been treatedADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.drugalcdep.2008.04.019", "ISSN" : "0376-8716", "PMID" : "18620818", "abstract" : "BACKGROUND Most alcoholism research in the U.S. uses convenience samples of treated alcoholics. The findings from treated samples have traditionally been applied to all alcoholics, including the 75% of alcoholics who are untreated. Improper generalization from select samples to an entire population is called 'Berkson's fallacy'. We compared untreated versus treated alcoholics, in order to ascertain whether both groups belonged to the same population with regard to psychiatric comorbidity. METHODS We compared psychiatric comorbidity in 1) active treatment-naive alcoholics (TNA; n=86) 2) treated long-term abstinent alcoholics (TAA; n=52) and 3) non-alcoholic controls (NAC;n=118). We examined lifetime and current diagnoses, lifetime symptom counts, and psychological measures in the anxiety, mood and externalizing disorder domains. RESULTS TNA did not differ from NAC in psychiatric diagnosis rates, were abnormal compared to NAC on all psychological measures, had more externalizing symptoms than NAC, and showed a strong trend for men to have more symptoms in the mood and anxiety domains. TAA compared to TNA had higher diagnosis rates (all domains), symptom counts (all domains), and psychological measures of deviance proneness, but were comparable to TNA on anxiety and mood psychological measures. CONCLUSIONS The abnormal thinking (psychological measures) in TNA (versus NAC) does not extend to behavior (symptoms) to the degree that it does in TAA. These results underline the importance of the use of subdiagnostic measures of psychiatric comorbidity in studies of alcoholics. The finding of lesser comorbidity in TNA versus TAA confirms the presence of Berkson's fallacy in generalizing from treated samples to all alcoholics.", "author" : [ { "dropping-particle" : "", "family" : "Sclafani", "given" : "Victoria", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Finn", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fein", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Drug and alcohol dependence", "id" : "ITEM-1", "issue" : "1-2", "issued" : { "date-parts" : [ [ "2008", "11", "1" ] ] }, "note" : "NULL", "page" : "115-22", "title" : "Treatment-naive active alcoholics have greater psychiatric comorbidity than normal controls but less than treated abstinent alcoholics.", "type" : "article-journal", "volume" : "98" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(134)", "plainTextFormattedCitation" : "(134)", "previouslyFormattedCitation" : "(134)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(134). Non-pharmacological treatments have also been widely used. Several psychosocial interventions have shown significant behavioral change in patients with alcohol dependence including cognitive behavioral therapy (CBT), alcohol behavior coupled therapy, 12-step therapist facilitated treatments, and motivational interviewing and support the recommendation of some type of drug counseling to assist patients in remissionADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1527-4160", "PMID" : "16728904", "abstract" : "While the U.S. Food and Drug Administration has approved several medications for the treatment of alcohol-related problems, their use has not gained wide acceptance in the United States. Typically, patients with alcohol use disorders are only referred to psychosocial support (e.g., Alcoholics Anonymous). However, the use of pharmacotherapy may complement psychosocial treatments, as evidence shows that pharmacotherapy can improve treatment outcomes. The effectiveness of pharmacotherapy depends on patient compliance with taking the medication and the context in which the medication is administered. BRENDA is a psychosocial program designed specifically to be used by many types of healthcare providers, including primary care clinicians. Designed to enhance medication and treatment compliance, BRENDA is an ideal approach for use in conjunction with pharmacotherapy. The BRENDA approach has 6 components: 1) a biopsychosocial evaluation; 2) a report of findings from the evaluation given to the patient; 3) empathy; 4) addressing patient needs; 5) providing direct advice; and 6) assessing patient reaction to advice and adjusting the treatment plan as needed. This paper describes these components and discusses how the empirical support for each component is linked to the enhancement of medication compliance and the improvement of treatment outcomes.", "author" : [ { "dropping-particle" : "", "family" : "Starosta", "given" : "Aron N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leeman", "given" : "Robert F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Volpicelli", "given" : "Joseph R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of psychiatric practice", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2006", "3" ] ] }, "note" : "NULL", "page" : "80-9", "title" : "The BRENDA model: integrating psychosocial treatment and pharmacotherapy for the treatment of alcohol use disorders.", "type" : "article-journal", "volume" : "12" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1111/acer.12848", "ISSN" : "1530-0277", "PMID" : "26344200", "abstract" : "BACKGROUND The current review revisits the article entitled: \"Active Ingredients: How and Why Evidence-Based Alcohol Behavioral Treatment Interventions Work\" published in Alcoholism: Clinical and Experimental Research. This work summarized proceedings from a 2004 Symposium of the same name that was held at the Annual Meeting of the Research Society on Alcoholism (RSA). A decade has passed, which provides occasion for an evaluation of progress. In 2014, an RSA symposium titled Active Treatment Ingredients and Client Mechanisms of Change in Behavioral Treatments for Alcohol Use Disorders: Progress 10\u00a0Years Later did just that. METHODS The current review revisits state-of-the-art research on the 3 treatments examined 10\u00a0years ago: cognitive behavioral therapy, alcohol behavior couples therapy, and 12-step facilitation. Because of its empirically validated effectiveness and robust research agenda on the study of process outcome, motivational interviewing has been selected as the fourth treatment modality to be discussed. For each of these 4 treatments, the reviewers provide a critical assessment of current theory and research with a special emphasis on key recommendations for the future. RESULTS Noteworthy progress has been made in identifying active ingredients of treatments and mechanisms of behavior change in these 4 behavioral interventions for alcohol and other drug use disorders. Not only have we established some of the mechanisms through which these evidence-based treatments work, but we have also uncovered some of the limitations in our existing frameworks and methods. CONCLUSIONS Further progress in this area will require a broader view with respect to conceptual frameworks, analytic methods, and measurement instrumentation.", "author" : [ { "dropping-particle" : "", "family" : "Magill", "given" : "Molly", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kiluk", "given" : "Brian D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCrady", "given" : "Barbara S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tonigan", "given" : "J Scott", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Longabaugh", "given" : "Richard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Alcoholism, clinical and experimental research", "id" : "ITEM-2", "issue" : "10", "issued" : { "date-parts" : [ [ "2015", "10" ] ] }, "note" : "NULL", "page" : "1852-62", "title" : "Active Ingredients of Treatment and Client Mechanisms of Change in Behavioral Treatments for Alcohol Use Disorders: Progress 10\u00a0Years Later.", "type" : "article-journal", "volume" : "39" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(135,136)", "plainTextFormattedCitation" : "(135,136)", "previouslyFormattedCitation" : "(135,136)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(135,136). A systematic review included 13 studies with psychosocial interventions in inducing or maintaining abstinence from alcohol in patients with chronic liver disease. Combined CBT, motivational enhancement therapy, and comprehensive medical care increased alcohol abstinence and combined CBT plus medical management reduced recidivismADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.cgh.2015.07.047", "ISSN" : "1542-7714", "PMID" : "26256464", "abstract" : "BACKGROUND & AIMS We conducted a systematic review of efficacy of psychosocial interventions in inducing or maintaining alcohol abstinence in patients with chronic liver disease (CLD) and alcohol use disorder (AUD). METHODS We performed structured keyword searches in PubMed, PsychINFO, and MEDLINE for original research articles that were published from January 1983 through November 2014 that evaluated the use of psychosocial interventions to induce or maintain alcohol abstinence in patients with CLD and AUD. RESULTS We identified 13 eligible studies that comprised 1945 patients; 5 were randomized controlled trials (RCTs). Delivered therapies included motivational enhancement therapy, cognitive behavioral therapy (CBT), motivational interviewing, supportive therapy, and psychoeducation either alone or in combination in the intervention group and general health education or treatment as usual in the control group. All studies of induction of abstinence (4 RCTs and 6 observational studies) reported an increase in abstinence among participants in the intervention and control groups. Only an integrated therapy that combined CBT and motivational enhancement therapy with comprehensive medical care, delivered during a period of 2 years, produced a significant increase in abstinence (74% increase in intervention group vs 48% increase in control group, P = .02), which was reported in 1 RCT. All studies of maintenance of abstinence (1 RCT and 2 observational studies) observed recidivism in the intervention and control groups. Only an integrated therapy that combined medical care with CBT produced a significantly smaller rate of recidivism (32.7% in integrated CBT group vs 75% in control group, P = .03), which was reported from 1 observational study. However, data were not collected for more than 2 years on outcomes of patients with CLD and AUD. CONCLUSIONS In a systematic analysis of studies of interventions to induce or maintain alcohol abstinence in patients with CLD and AUD, integrated combination psychotherapy with CBT, motivational enhancement therapy, and comprehensive medical care increased alcohol abstinence. No psychosocial intervention was successful in maintaining abstinence, but an integrated therapy with CBT and medical care appears to reduce recidivism.", "author" : [ { "dropping-particle" : "", "family" : "Khan", "given" : "Anam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tansel", "given" : "Aylin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "White", "given" : "Donna L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kayani", "given" : "Waleed Tallat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bano", "given" : "Shah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindsay", "given" : "Jan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "El-Serag", "given" : "Hashem B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kanwal", "given" : "Fasiha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2016", "2" ] ] }, "note" : "NULL", "page" : "191-202.e1-4; quiz e20", "title" : "Efficacy of Psychosocial Interventions in Inducing and Maintaining Alcohol Abstinence in Patients With Chronic Liver\u00a0Disease: A Systematic Review.", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(137)", "plainTextFormattedCitation" : "(137)", "previouslyFormattedCitation" : "(137)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(137). Mutual help and self-help organizations such as Alcoholics Anonymous can be helpful for many patients to provide support for recovery and facilitate the formation of new social connections but are not considered formal treatment and have not been extensively studied as part of randomized controlled trialsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/14651858.CD005032.pub2", "ISSN" : "1469-493X", "PMID" : "16856072", "abstract" : "BACKGROUND Alcoholics Anonymous (AA) is an international organization of recovering alcoholics that offers emotional support through self-help groups and a model of abstinence for people recovering from alcohol dependence, using a 12-step approach. Although it is the most common, AA is not the only 12-step intervention available there are other 12-step approaches (labelled Twelve Step Facilitation (TSF)). OBJECTIVES To assess the effectiveness of AA or TSF programmes compared to other psychosocial interventions in reducing alcohol intake, achieving abstinence, maintaining abstinence, improving the quality of life of affected people and their families, and reducing alcohol associated accidents and health problems. SEARCH STRATEGY We searched the Specialized Register of Trials of the Cochrane Group on Drugs and Alcohol, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE from 1966, EMBASE from 1980, CINAHL from 1982, PsychINFO from 1967. Searches were updated in February 2005. We also inspected lists of references for relevant studies. SELECTION CRITERIA Studies involving adults (<18) of both genders with alcohol dependence attending on a voluntary or coerced basis AA or TSF programmes comparing no treatment, other psychological interventions, 12-step variants. DATA COLLECTION AND ANALYSIS One reviewer (MF) assessed studies for inclusion and extracted data using a pre-defined data extraction form. Studies were evaluated for methodological quality and discussed by all reviewers. MAIN RESULTS Eight trials involving 3417 people were included. AA may help patients to accept treatment and keep patients in treatment more than alternative treatments, though the evidence for this is from one small study that combined AA with other interventions and should not be regarded as conclusive. Other studies reported similar retention rates regardless of treatment group. Three studies compared AA combined with other interventions against other treatments and found few differences in the amount of drinks and percentage of drinking days. Severity of addiction and drinking consequence did not seem to be differentially influenced by TSF versus comparison treatment interventions, and no conclusive differences in treatment drop out rates were reported. Included studies did not allow a conclusive assessment of the effect of TSF in promoting complete abstinence. AUTHORS' CONCLUSIONS No experimental studies unequivocally demonstrated the effectiveness of AA or TS\u2026", "author" : [ { "dropping-particle" : "", "family" : "Ferri", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Amato", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davoli", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Cochrane database of systematic reviews", "editor" : [ { "dropping-particle" : "", "family" : "Ferri", "given" : "Marica", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2006", "7", "19" ] ] }, "note" : "NULL", "page" : "CD005032", "publisher" : "John Wiley & Sons, Ltd", "publisher-place" : "Chichester, UK", "title" : "Alcoholics Anonymous and other 12-step programmes for alcohol dependence.", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(138)", "plainTextFormattedCitation" : "(138)", "previouslyFormattedCitation" : "(138)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(138). Tobacco: Several studies have shown that smoking tobacco, particularly cigarettes increased the risk for developing both acuteADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/MPA.0000000000000176", "ISSN" : "1536-4828", "PMID" : "25333404", "abstract" : "We aimed to better understand the relationship between smoking and a risk for acute pancreatitis (AP) in existing observational studies. We identified studies by searching the PubMed, Scopus, and Web of Science databases (from inception through August 31, 2013) and by searching bibliographies of relevant articles. Summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated with fixed-effects and random-effects models. A total of 5 studies met inclusion criteria for analysis. Both current smoking (summary RR, 1.74; 95% CI, 1.39-2.17; n = 5 studies) and former smoking (summary RR, 1.32; 95% CI, 1.03-1.71; n = 4 studies) were associated with an increased risk for AP. The positive association of current smoking and risk for AP remained when we limited the meta-analysis to studies that controlled for alcohol intake and body mass index (summary RR, 1.76; 95% CI, 1.31-2.36; n = 4 studies). Both current and former smoking are associated with increased risk for AP. Further investigations, both epidemiological and mechanistic, are needed to establish the extent to which the association can be explained by a causal link and whether smoking cessation can prevent the occurrence and development of AP.", "author" : [ { "dropping-particle" : "", "family" : "Yuhara", "given" : "Hiroki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ogawa", "given" : "Masami", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kawaguchi", "given" : "Yoshiaki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Igarashi", "given" : "Muneki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mine", "given" : "Tetsuya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreas", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2014", "11" ] ] }, "note" : "NULL", "page" : "1201-7", "title" : "Smoking and risk for acute pancreatitis: a systematic review and meta-analysis.", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.pan.2015.03.001", "ISSN" : "1424-3911", "PMID" : "25804129", "abstract" : "BACKGROUND AND AIM Questions remain unclear about the association of smoking status and the development of acute pancreatitis (AP). We performed a meta-analysis of observational studies explore this association. METHODS A computerized literature search was performed in MEDLINE and EMBASE through November 30, 2014. We also searched the reference lists of pertinent articles. We used a random-effects model to calculate the summary relative risks (SRRs) and their corresponding 95% confidence intervals (CIs). RESULTS A total of 3690 incident cases of AP included 12 observational studies (6 case-control and 6 prospective cohort/nested case-control studies) were identified. Compared with never smokers, the summary RR estimates were 1.54 (95% CI, 1.31-1.80) for ever smokers, 1.71 (95% CI, 1.37-2.14) for current smokers, and 1.21 (95% CI, 1.02-1.43) for former smokers. Smoking is found to be a potential risk factor for alcohol use, idiopathic factors and drugs related AP, but not for gallstone related AP, in the ever and current smokers. A dose-response effect of tobacco use on the risk was ascertained: current smokers had a 40% (95% CI, 30%-51%) increased risk of AP for every additional 10 cigarettes per day. CONCLUSION The present analysis suggests that smokers have an elevated risk of AP development. Further studies, however, are warranted before definitive conclusions can be drawn.", "author" : [ { "dropping-particle" : "", "family" : "Sun", "given" : "Xiaobing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huang", "given" : "Xiaoquan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Ruifeng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Beibei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xie", "given" : "Qin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2015", "5" ] ] }, "note" : "NULL", "page" : "286-94", "title" : "Meta-analysis: Tobacco smoking may enhance the risk of acute pancreatitis.", "type" : "article-journal", "volume" : "15" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(139,140)", "plainTextFormattedCitation" : "(139,140)", "previouslyFormattedCitation" : "(139,140)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(139,140) and chronic pancreatitisADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1159/000332196", "ISSN" : "1424-3911", "PMID" : "21986098", "abstract" : "BACKGROUND/AIMS Cigarette smoking has been linked to many diseases, including pancreatic cancer and more recently, pancreatitis. METHODS Electronic searches of primarily PubMed from 1990 to August 2011 were conducted and only articles published in English were reviewed. Original articles and reviews were selected based on screening of article abstracts and their relevance to tobacco smoking, its components, nicotine and its metabolites, and their effects particularly on the pancreas. RESULTS Smoking may affect the risk of developing chronic pancreatitis or its progression. Smoking may also affect the risk for developing acute pancreatitis. Its effects in pancreatitis appear to be dose dependent and its effects may be alcohol independent but synergize with alcohol. CONCLUSION Specific constituents of cigarette smoke, including nicotine and its metabolites, could mediate effects on the pancreas.", "author" : [ { "dropping-particle" : "", "family" : "Alexandre", "given" : "Martine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pandol", "given" : "Stephen J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gorelick", "given" : "Fred S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thrower", "given" : "Edwin C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2011", "1" ] ] }, "note" : "NULL", "page" : "469-74", "title" : "The emerging role of smoking in the development of pancreatitis.", "type" : "article-journal", "volume" : "11" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.4236/jct.2013.410A005", "ISSN" : "2151-1934", "PMID" : "24660091", "abstract" : "Smoking is a major risk factor for chronic pancreatitis and pancreatic cancer. However, the mechanisms through which it causes the diseases remain unknown. In the present manuscript we reviewed the latest knowledge gained on the effect of cigarette smoke and smoking compounds on cell signaling pathways mediating both diseases. We also reviewed the effect of smoking on the pancreatic cell microenvironment including inflammatory cells and stellate cells.", "author" : [ { "dropping-particle" : "", "family" : "Edderkaoui", "given" : "Mouad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thrower", "given" : "Edwin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of cancer therapy", "id" : "ITEM-2", "issue" : "10A", "issued" : { "date-parts" : [ [ "2013", "11", "1" ] ] }, "note" : "NULL", "page" : "34-40", "title" : "Smoking and Pancreatic Disease.", "type" : "article-journal", "volume" : "4" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1371/journal.pone.0124075", "ISSN" : "1932-6203", "PMID" : "25879541", "abstract" : "BACKGROUND AND OBJECTIVE Cigarette smoking may increase the risk of developing pancreatic cancer, although its impact on pancreatitis has only been discerned in recent years. However, the results of previous studies differ. We performed a meta-analysis to provide a quantitative pooled risk estimate of the association of cigarette smoking with pancreatitis. METHOD A literature search of the MEDLINE and Embase databases was conducted, and studies were selected that investigated the association of cigarette smoking with pancreatitis. Summary relative risks (RRs) with 95% confidence intervals (CIs) were pooled using a random-effects model. RESULTS Twenty-two studies were included. The summary RRs (95% CI) associated with ever, current and former smokers for acute and chronic pancreatitis (AP/CP) were as follows: 1.51 (1.10, 2.07)/3.00 (1.46, 6.17), 1.42 (1.08, 1.87)/2.72 (1.74, 4.24), and 1.22 (0.99, 1.52)/1.27 (1.00, 1.62), respectively. Moreover, studies that analyzed both AP and CP were also summarized: 1.73 (1.18, 2.54) for ever smokers, 1.67 (1.03, 2.68) for current smokers and 1.56 (1.16, 2.11) for former smokers, respectively. There was no evidence of publication bias across the studies. CONCLUSION The evidence suggests a positive association of cigarette smoking with the development of pancreatitis. It is possible that smoking cessation may be a useful strategy for the management of pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Ye", "given" : "Xiaohua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lu", "given" : "Guangrong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huai", "given" : "Jiaping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ding", "given" : "Jin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "editor" : [ { "dropping-particle" : "", "family" : "Katoh", "given" : "Masaru", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-3", "issue" : "4", "issued" : { "date-parts" : [ [ "2015", "4", "16" ] ] }, "note" : "NULL", "page" : "e0124075", "title" : "Impact of smoking on the risk of pancreatitis: a systematic review and meta-analysis.", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(141\u2013143)", "plainTextFormattedCitation" : "(141\u2013143)", "previouslyFormattedCitation" : "(141\u2013143)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(141–143) and this relative risk is dose-dependent. While cigarette smoking is often present in alcohol abuse, studies showing smoking as an independent predictive factor are emergingADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/MPA.0000000000000176", "ISSN" : "1536-4828", "PMID" : "25333404", "abstract" : "We aimed to better understand the relationship between smoking and a risk for acute pancreatitis (AP) in existing observational studies. We identified studies by searching the PubMed, Scopus, and Web of Science databases (from inception through August 31, 2013) and by searching bibliographies of relevant articles. Summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated with fixed-effects and random-effects models. A total of 5 studies met inclusion criteria for analysis. Both current smoking (summary RR, 1.74; 95% CI, 1.39-2.17; n = 5 studies) and former smoking (summary RR, 1.32; 95% CI, 1.03-1.71; n = 4 studies) were associated with an increased risk for AP. The positive association of current smoking and risk for AP remained when we limited the meta-analysis to studies that controlled for alcohol intake and body mass index (summary RR, 1.76; 95% CI, 1.31-2.36; n = 4 studies). Both current and former smoking are associated with increased risk for AP. Further investigations, both epidemiological and mechanistic, are needed to establish the extent to which the association can be explained by a causal link and whether smoking cessation can prevent the occurrence and development of AP.", "author" : [ { "dropping-particle" : "", "family" : "Yuhara", "given" : "Hiroki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ogawa", "given" : "Masami", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kawaguchi", "given" : "Yoshiaki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Igarashi", "given" : "Muneki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mine", "given" : "Tetsuya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreas", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2014", "11" ] ] }, "note" : "NULL", "page" : "1201-7", "title" : "Smoking and risk for acute pancreatitis: a systematic review and meta-analysis.", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0885-3177", "PMID" : "10975702", "abstract" : "We conducted a hospital-based, case-control study to examine the association of cigarette smoking with chronic pancreatitis. Ninety-one male patients with chronic pancreatitis newly diagnosed from July 1997 to December 1998 were recruited as cases, and 175 controls were individually matched to each case for gender, age (+/- 5 years), hospital, and time of the first visit to a hospital (+/- 1 year). A self-administered questionnaire was used to collect information on tobacco and alcohol use, diet, and other factors. The odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated by multiple conditional logistic models, adjusting for body mass index, education level, and alcohol consumption. Compared with nonsmokers, the ORs (95% CIs) were 7.8 (2.2-27.3) for all current smokers, and 14.7 (3.1-69.9), 5.5 (1.5-20.1), 12.2 (2.4-71.0) for those consuming < 20, 20-39, and > or = 40 cigarettes per day, respectively. Much greater risk was observed for those who had smoked for > or = 25 years. Risk of chronic pancreatitis significantly increased with increasing cumulative amount of smoking (p < 0.05). Analysis for the effect of combined use of tobacco and alcohol showed that cigarette smoking was associated with the higher risk in both of the two alcohol consumption levels. Our findings indicated that cigarette smoking may be an independent and significant risk factor for chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Lin", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tamakoshi", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayakawa", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ogawa", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ohno", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreas", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2000", "8" ] ] }, "note" : "NULL", "page" : "109-14", "title" : "Cigarette smoking as a risk factor for chronic pancreatitis: a case-control study in Japan. Research Committee on Intractable Pancreatic Diseases.", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISBN" : "1538-3679; 0003-9926", "abstract" : "BACKGROUND: Alcohol and gallstone disease are the most established risk factors for pancreatitis. Smoking is rarely considered to be a cause despite the fact that a few studies have indicated the opposite. We aimed to assess the independent effects of smoking on the risk of pancreatitis. METHODS: We used data from an observational, population-based cohort study conducted in Denmark. Participants were 9573 women and 8332 men who were followed up for a mean of 20.2 years. Participants underwent a physical examination and completed self-administered questionnaires about lifestyle habits. Information on incident cases of acute and chronic pancreatitis were obtained by record linkage with the Danish national registries. RESULTS: A total of 235 cases of pancreatitis occurred during follow-up. A dose-response association between smoking and risk of acute and chronic pancreatitis was observed in both men and women. For example, the hazard ratio of developing pancreatitis was 2.6 (95% confidence interval [CI], 1.5-4.7) among women and 2.6 (95% CI, 1.1-6.2) among men who smoked 15 to 24 grams of tobacco per day. Alcohol intake was associated with an increased risk of pancreatitis (hazard ratio, 1.09; 95% CI, 1.04-1.14 for each additional drink per day). The risk of pancreatitis associated with smoking, however, was independent of alcohol and gallstone disease. Approximately 46% of cases of pancreatitis were attributable to smoking in this cohort. CONCLUSION: In this population of Danish men and women, smoking was independently associated with increased risk of pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Tolstrup", "given" : "J S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kristiansen", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Becker", "given" : "U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gronbaek", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Archives of Internal Medicine", "id" : "ITEM-3", "issue" : "6", "issued" : { "date-parts" : [ [ "2009", "3" ] ] }, "note" : "NULL", "page" : "603-609", "title" : "Smoking and risk of acute and chronic pancreatitis among women and men: a population-based cohort study", "type" : "article-journal", "volume" : "169" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1097/MPA.0b013e3181df27c0", "ISSN" : "1536-4828", "PMID" : "20622705", "abstract" : "OBJECTIVES To assess the evidence for tobacco smoking as a risk factor for the causation of chronic pancreatitis. METHODS We performed a meta-analysis with random-effects models to estimate pooled relative risks (RRs) of chronic pancreatitis for current, former, and ever smokers, in comparison to never smokers. We also performed dose-response, heterogeneity, publication bias, and sensitivity analyses. RESULTS Ten case-control studies and 2 cohort studies that evaluated, overall, 1705 patients with chronic pancreatitis satisfied the inclusion criteria. When contrasted to never smokers, the pooled risk estimates for current smokers was 2.8 (95% confidence interval [CI], 1.8-4.2) overall and 2.5 (95% CI, 1.3-4.6) when data were adjusted for alcohol consumption. A dose-response effect of tobacco use on the risk was ascertained: the RR for subjects smoking less than 1 pack per day was 2.4 (95% CI, 0.9-6.6) and increased to 3.3 (95% CI, 1.4-7.9) in those smoking 1 or more packs per day. The risk diminished significantly after smoking cessation, as the RR estimate for former smokers dropped to a value of 1.4 (95% CI, 1.1-1.9). CONCLUSIONS Tobacco smoking may enhance the risk of developing chronic pancreatitis. Recommendation for smoking cessation, besides alcohol abstinence, should be incorporated in the management of patients with chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Andriulli", "given" : "Angelo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Botteri", "given" : "Edoardo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Almasio", "given" : "Piero L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vantini", "given" : "Italo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uomo", "given" : "Generoso", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maisonneuve", "given" : "Patrick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "ad hoc Committee of the Italian Association for the Study of the Pancreas", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreas", "id" : "ITEM-4", "issue" : "8", "issued" : { "date-parts" : [ [ "2010", "11" ] ] }, "page" : "1205-10", "title" : "Smoking as a cofactor for causation of chronic pancreatitis: a meta-analysis.", "type" : "article-journal", "volume" : "39" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(139,144\u2013146)", "plainTextFormattedCitation" : "(139,144\u2013146)", "previouslyFormattedCitation" : "(139,144\u2013146)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(139,144–146). Prospective studies evaluating the effects of smoking cessation on chronic pain are lacking, but smoking was associated with the chronification of pain in other pain syndromesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/hbm.22656", "ISSN" : "1097-0193", "PMID" : "25307796", "abstract" : "Smoking is associated with increased incidence of chronic pain. However, the evidence is cross-sectional in nature, and underlying mechanisms remain unclear. In a longitudinal observational study, we examined the relationship between smoking, transition to chronic pain, and brain physiology. In 160 subjects with subacute back pain (SBP: back pain lasting 4-12 weeks, and no prior back pain [BP] for at least 1 year) pain characteristics, smoking status, and brain functional properties were measured repeatedly over 1 year. Sixty-eight completed the study, subdivided into recovering (SBPr, n\u2009=\u200931) and persisting (SBPp, n\u2009=\u200937), based on >20% decrease in BP over the year. Thirty-two chronic back pain (CBP: duration\u2009>\u20095 years) and 35 healthy controls were similarly monitored. Smoking prevalence was higher in SBP and CBP but not related to intensity of BP. In SBP, smoking status at baseline was predictive of persistence of BP 1 year from symptom onset (differentiating SBPp and SBPr with 0.62 accuracy). Smoking status combined with affective properties of pain and medication use improved prediction accuracy (0.82). Mediation analysis indicated the prediction of BP persistence by smoking was largely due to synchrony of fMRI activity between two brain areas (nucleus accumbens and medial prefrontal cortex, NAc-mPFC). In SBP or CBP who ceased smoking strength of NAc-mPFC decreased from precessation to postcessation of smoking. We conclude that smoking increases risk of transitioning to CBP, an effect mediated by corticostriatal circuitry involved in addictive behavior and motivated learning.", "author" : [ { "dropping-particle" : "", "family" : "Petre", "given" : "Bogdan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Torbey", "given" : "Souraya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Griffith", "given" : "James W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oliveira", "given" : "Gildasio", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herrmann", "given" : "Kristine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mansour", "given" : "Ali", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baria", "given" : "Alex T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baliki", "given" : "Marwan N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schnitzer", "given" : "Thomas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Apkarian", "given" : "Apkar Vania", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Human brain mapping", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2015", "2" ] ] }, "page" : "683-94", "title" : "Smoking increases risk of pain chronification through shared corticostriatal circuitry.", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(147)", "plainTextFormattedCitation" : "(147)", "previouslyFormattedCitation" : "(147)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(147). As for alcohol use the health risks of smoking, including acceleration of disease progression, still makes abstinence advisable. Unfortunately, chronic pain has been associated with greater challenges in smoking cessation ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s12160-016-9769-9", "ISSN" : "1532-4796", "PMID" : "26813264", "abstract" : "BACKGROUND Chronic pain and tobacco smoking are both highly prevalent and comorbid conditions, and chronic pain may pose a barrier to smoking cessation. PURPOSE The objective of this study was to test associations between chronic pain status and several smoking-related factors that have previously been shown to predict cessation outcomes. METHOD Daily smokers (N\u2009=\u2009205) were recruited from the general population to complete an online survey of pain and tobacco smoking. RESULTS Results indicated that smokers with chronic pain (vs. no chronic pain) consumed more cigarettes per day, scored higher on an established measure of tobacco dependence, reported having less confidence in their ability to quit, and endorsed expectations for experiencing greater difficulty and more severe nicotine withdrawal during future cessation attempts. Mediation analyses further indicated that the inverse association between chronic pain and abstinence self-efficacy was indirectly influenced by past cessation failures. CONCLUSIONS These findings suggest that individuals with chronic pain may constitute an important subgroup of tobacco smokers who tend to experience lower confidence and greater difficulty when attempting to quit. Future research would benefit from replicating these findings among older and more diverse samples of heavier tobacco smokers, and extending this work to the study of prospective relations between chronic pain status and cessation-relevant processes/outcomes over the course of a quit attempt.", "author" : [ { "dropping-particle" : "", "family" : "Ditre", "given" : "Joseph W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kosiba", "given" : "Jesse D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zale", "given" : "Emily L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zvolensky", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maisto", "given" : "Stephen A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of behavioral medicine : a publication of the Society of Behavioral Medicine", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2016", "6", "26" ] ] }, "page" : "427-35", "title" : "Chronic Pain Status, Nicotine Withdrawal, and Expectancies for Smoking Cessation Among Lighter Smokers.", "type" : "article-journal", "volume" : "50" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1097/MPA.0000000000000641", "ISSN" : "1536-4828", "PMID" : "27101574", "abstract" : "OBJECTIVES Smoking is a known risk factor for developing chronic pancreatitis and accelerates disease progression. Smoking cessation remains an important treatment recommendation, but little is known about its effects. This study evaluated smoking cessation in this population and its impact on quality of life. METHODS Twenty-seven smokers with chronic pancreatitis participated in a smoking cessation program incorporating the QuitWorks program and individual counseling. Their smoking cessation rates were compared with a control population (n = 200) consisting of inpatients without chronic pancreatitis who smoked. Smokers were also compared with nonsmokers (n = 25) with chronic pancreatitis in terms of quality-of-life indicators. RESULTS In 27 patients, 0 had quit smoking at 6 months, 1 at 12 months, and 0 patients at 18 months. There was a 19% quit rate in the control population at the 6-month period. Smokers had a worse quality of life, higher rates of depression and anxiety, and worse coping skills than nonsmokers. CONCLUSIONS Smoking cessation in the chronic pancreatitis population is extremely challenging, as shown by our 0% quit rate after 18 months. Given that smokers with chronic pancreatitis also experience a worse quality of life, it becomes even more important to stress the importance of smoking cessation in these patients.", "author" : [ { "dropping-particle" : "", "family" : "Han", "given" : "Samuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kheder", "given" : "Joan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bocelli", "given" : "Lisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fahed", "given" : "Julien", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wachholtz", "given" : "Amy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seward", "given" : "Gregory", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wassef", "given" : "Wahid", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreas", "id" : "ITEM-2", "issue" : "9", "issued" : { "date-parts" : [ [ "2016", "10" ] ] }, "page" : "1303-8", "title" : "Smoking Cessation in a Chronic Pancreatitis Population.", "type" : "article-journal", "volume" : "45" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(148,149)", "plainTextFormattedCitation" : "(148,149)", "previouslyFormattedCitation" : "(148,149)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(148,149). More than 80% of patients with alcoholic chronic pancreatitis are smokers and smoking potentiates alcohol toxicity in dose-dependent wayADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.4236/jct.2013.410A005", "ISSN" : "2151-1934", "PMID" : "24660091", "abstract" : "Smoking is a major risk factor for chronic pancreatitis and pancreatic cancer. However, the mechanisms through which it causes the diseases remain unknown. In the present manuscript we reviewed the latest knowledge gained on the effect of cigarette smoke and smoking compounds on cell signaling pathways mediating both diseases. We also reviewed the effect of smoking on the pancreatic cell microenvironment including inflammatory cells and stellate cells.", "author" : [ { "dropping-particle" : "", "family" : "Edderkaoui", "given" : "Mouad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thrower", "given" : "Edwin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of cancer therapy", "id" : "ITEM-1", "issue" : "10A", "issued" : { "date-parts" : [ [ "2013", "11", "1" ] ] }, "note" : "NULL", "page" : "34-40", "title" : "Smoking and Pancreatic Disease.", "type" : "article-journal", "volume" : "4" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(142)", "plainTextFormattedCitation" : "(142)", "previouslyFormattedCitation" : "(142)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(142). Cigarette smoking has been shown to accelerate the progression of alcoholic pancreatitis, with appearance of calcifications, and diabetes and this effect was independent of amount of alcohol consumptionADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/gut.2004.039263", "ISSN" : "0017-5749", "author" : [ { "dropping-particle" : "", "family" : "Maisonneuve", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gut", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2005", "4", "1" ] ] }, "note" : "NULL", "page" : "510-514", "title" : "Cigarette smoking accelerates progression of alcoholic chronic pancreatitis", "type" : "article-journal", "volume" : "54" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(150)", "plainTextFormattedCitation" : "(150)", "previouslyFormattedCitation" : "(150)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(150). The exact mechanisms by which tobacco metabolites affect the pancreas are unknown. Substances from smoking which have been considered as causal agents include tobacco-specific metabolites such as NNK and nitrosamines as well as nicotine specific metabolites such as NNN and DENADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.4236/jct.2013.410A005", "ISSN" : "2151-1934", "PMID" : "24660091", "abstract" : "Smoking is a major risk factor for chronic pancreatitis and pancreatic cancer. However, the mechanisms through which it causes the diseases remain unknown. In the present manuscript we reviewed the latest knowledge gained on the effect of cigarette smoke and smoking compounds on cell signaling pathways mediating both diseases. We also reviewed the effect of smoking on the pancreatic cell microenvironment including inflammatory cells and stellate cells.", "author" : [ { "dropping-particle" : "", "family" : "Edderkaoui", "given" : "Mouad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thrower", "given" : "Edwin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of cancer therapy", "id" : "ITEM-1", "issue" : "10A", "issued" : { "date-parts" : [ [ "2013", "11", "1" ] ] }, "note" : "NULL", "page" : "34-40", "title" : "Smoking and Pancreatic Disease.", "type" : "article-journal", "volume" : "4" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(142)", "plainTextFormattedCitation" : "(142)", "previouslyFormattedCitation" : "(142)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(142). One hypothesis is that nicotine results in high levels of intracellular calcium release which causes cytotoxicityADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1535-3702", "PMID" : "12094008", "abstract" : "Epidemiological evidence strongly suggests an association between cigarette smoking and pancreatic diseases. It is well recognized that nicotine, a major component in cigarette smoke, is an addictive agent and, therefore, reinforces smoking behavior. The current review update focuses on the genetics of nicotine dependence and its role on the development of pancreatic diseases. The role of smoking and nicotine in pancreatitis and pancreatic cancer development is also discussed. Exposure of laboratory animals to nicotine clearly supports the notion that nicotine can induce pancreatic injury. The mechanism by which nicotine induces such effects is perhaps mediated via signal transduction pathways in the pancreatic acinar cell, leading to enhanced levels of intracellular calcium release, resulting in cytotoxicity and eventual cell death. The induction of pancreatic injury by nicotine may also involve activation and expression of protooncogene, H-ras, which can increase cytosolic calcium via second messenger pathways. Development of pancreatic carcinoma in cigarette smokers as observed in human populations may be the result of activation and mutation of the H-ras gene. A possible pathogenetic mechanism of nicotine in the pancreas activating multiple signal transduction pathways is schematically summarized in Figure 1.", "author" : [ { "dropping-particle" : "", "family" : "Chowdhury", "given" : "Parimal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "MacLeod", "given" : "Stewart", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Udupa", "given" : "Kodetthor B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rayford", "given" : "Phillip L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Experimental biology and medicine (Maywood, N.J.)", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2002", "7" ] ] }, "note" : "NULL", "page" : "445-54", "title" : "Pathophysiological effects of nicotine on the pancreas: an update.", "type" : "article-journal", "volume" : "227" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(151)", "plainTextFormattedCitation" : "(151)", "previouslyFormattedCitation" : "(151)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(151). Pharmacological treatment: Logically, smoking cessation should be a strong recommendation for patients with chronic pancreatitis. Although cessation of smoking has been shown to reduce the risk of developing pancreatitisADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/gutjnl-2011-300566", "ISSN" : "0017-5749", "author" : [ { "dropping-particle" : "", "family" : "Sadr-Azodi", "given" : "O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andr\u00e9n-Sandberg", "given" : "\u00c5", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Orsini", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wolk", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gut", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2012", "2" ] ] }, "note" : "NULL", "page" : "262-267", "title" : "Cigarette smoking, smoking cessation and acute pancreatitis: a prospective population-based study", "type" : "article-journal", "volume" : "61" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(152)", "plainTextFormattedCitation" : "(152)", "previouslyFormattedCitation" : "(152)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(152), no study has evaluated the effect of smoking cessation on pain in patients with CP. Given that nicotine is addicting, several medications can help with cravings such as bupropion, which can also be safely combined with nicotine replacement therapies if necessary. In a recent double blind parallel group, bupropion plus naltrexone outperformed bupropion plus placebo in smoking abstinence at 7 weeks but not 6 monthsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/cpt.402", "ISSN" : "1532-6535", "PMID" : "27213949", "abstract" : "Combination of non-nicotine pharmacotherapies has been underexamined for cigarette smoking cessation. A randomized, double-blind, parallel-group double-dummy study evaluated two medications, bupropion (BUP) and naltrexone (NTX), in treatment-seeking cigarette smokers (N = 121) over a 7-week treatment intervention with 6-month follow-up. Smokers were randomized to either BUP (300 mg/day) + placebo (PBO) or BUP (300 mg/day) + NTX (50 mg/day). The primary outcome was biochemically verified (saliva cotinine, carbon monoxide) 7-day, point-prevalence abstinence. BUP + NTX was associated with significantly higher point-prevalence abstinence rates after 7-weeks of treatment (BUP + NTX, 54.1%; BUP + PBO, 33.3%), P = 0.0210, but not at 6-month follow-up (BUP + NTX, 27.9%; BUP + PBO, 15.0%), P = 0.09. Continuous abstinence rates did not differ, P = 0.0740 (BUP + NTX, 26.2%; BUP + PBO, 13.3%). Those receiving BUP + NTX reported reduced nicotine withdrawal, P = 0.0364. The BUP + NTX combination was associated with elevated rates of some side effects, but with no significant difference in retention between the groups.", "author" : [ { "dropping-particle" : "", "family" : "Mooney", "given" : "M E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schmitz", "given" : "J M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Allen", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grabowski", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pentel", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oliver", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hatsukami", "given" : "D K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical pharmacology and therapeutics", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2016", "10" ] ] }, "note" : "NULL", "page" : "344-52", "title" : "Bupropion and naltrexone for smoking cessation: A double-blind randomized placebo-controlled clinical trial.", "type" : "article-journal", "volume" : "100" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(153)", "plainTextFormattedCitation" : "(153)", "previouslyFormattedCitation" : "(153)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(153). Varenicline, a partial nicotine agonist, has been shown to enhance smoking abstinence through reduction of smoking compared to placeboADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1001/jama.2015.280", "ISSN" : "0098-7484", "PMID" : "25688780", "abstract" : "IMPORTANCE Some cigarette smokers may not be ready to quit immediately but may be willing to reduce cigarette consumption with the goal of quitting. OBJECTIVE To determine the efficacy and safety of varenicline for increasing smoking abstinence rates through smoking reduction. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind, placebo-controlled, multinational clinical trial with a 24-week treatment period and 28-week follow-up conducted between July 2011 and July 2013 at 61 centers in 10 countries. The 1510 participants were cigarette smokers who were not willing or able to quit smoking within the next month but willing to reduce smoking and make a quit attempt within the next 3 months. Participants were recruited through advertising. INTERVENTIONS Twenty-four weeks of varenicline titrated to 1 mg twice daily or placebo with a reduction target of 50% or more in number of cigarettes smoked by 4 weeks, 75% or more by 8 weeks, and a quit attempt by 12 weeks. MAIN OUTCOMES AND MEASURES Primary efficacy end point was carbon monoxide-confirmed self-reported abstinence during weeks 15 through 24. Secondary outcomes were carbon monoxide-confirmed self-reported abstinence for weeks 21 through 24 and weeks 21 through 52. RESULTS The varenicline group (n\u2009=\u2009760) had significantly higher continuous abstinence rates during weeks 15 through 24 vs the placebo group (n\u2009=\u2009750) (32.1% for the varenicline group vs 6.9% for the placebo group; risk difference (RD), 25.2% [95% CI, 21.4%-29.0%]; relative risk (RR), 4.6 [95% CI, 3.5-6.1]). The varenicline group had significantly higher continuous abstinence rates vs the placebo group during weeks 21 through 24 (37.8% for the varenicline group vs 12.5% for the placebo group; RD, 25.2% [95% CI, 21.1%-29.4%]; RR, 3.0 [95% CI, 2.4-3.7]) and weeks 21 through 52 (27.0% for the varenicline group vs 9.9% for the placebo group; RD, 17.1% [95% CI, 13.3%-20.9%]; RR, 2.7 [95% CI, 2.1-3.5]). Serious adverse events occurred in 3.7% of the varenicline group and 2.2% of the placebo group (P\u2009=\u2009.07). CONCLUSIONS AND RELEVANCE Among cigarette smokers not willing or able to quit within the next month but willing to reduce cigarette consumption and make a quit attempt at 3 months, use of varenicline for 24 weeks compared with placebo significantly increased smoking cessation rates at the end of treatment, and also at 1 year. Varenicline offers a treatment option for smokers whose needs are not addressed by clinical guidelines recommending\u2026", "author" : [ { "dropping-particle" : "", "family" : "Ebbert", "given" : "Jon O.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hughes", "given" : "John R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "West", "given" : "Robert J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rennard", "given" : "Stephen I.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Russ", "given" : "Cristina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McRae", "given" : "Thomas D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Treadow", "given" : "Joan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yu", "given" : "Ching-Ray", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dutro", "given" : "Michael P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Park", "given" : "Peter W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "JAMA", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2015", "2", "17" ] ] }, "note" : "NULL", "page" : "687", "title" : "Effect of Varenicline on Smoking Cessation Through Smoking Reduction", "type" : "article-journal", "volume" : "313" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(154)", "plainTextFormattedCitation" : "(154)", "previouslyFormattedCitation" : "(154)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(154). Varenicline together with nicotine replacement therapy enhance early and medium-term smoking cessation but did not outperform nicotine replacement in the longer-termADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1186/s12916-016-0626-2", "ISSN" : "1741-7015", "PMID" : "27233840", "abstract" : "BACKGROUND Extended use of combined pharmacotherapies to treat tobacco dependence may increase smoking abstinence; few studies have examined their effectiveness. The objective of this study was to evaluate smoking abstinence with standard nicotine patch (NRT), extended use of combined formulations of nicotine replacement therapy (NRT+), or varenicline (VR). METHODS A total of 737 smokers, including those with medical and psychiatric comorbidities, were randomly assigned to one of the above three treatment conditions. The NRT group received 10 weeks of patches (21 mg daily maximum); the NRT+ group received patches (35 mg daily maximum) and gum or inhaler for up to 22 weeks; and the VR group received 1 mg twice daily for up to 24 weeks (22 weeks post target quit date). All participants also received six standardized 15-minute smoking cessation counseling sessions by nurses experienced in tobacco dependence treatment. The primary outcome was carbon monoxide-confirmed continuous abstinence rates (CAR) from weeks 5-52. Secondary outcomes were: CAR from weeks 5-10 and 5-22, and carbon monoxide-confirmed 7-day point prevalence (7PP) at weeks 10, 22, and 52. Adjusted and unadjusted logistic regression analyses were conducted using intention-to-treat procedures. RESULTS The CARs for weeks 5-52 were 10.0 %, 12.4 %, and 15.3 % in the NRT, NRT+, and VR groups, respectively; no group differences were observed. Results with 7PP showed that VR was superior to NRT at week 52 (odds ratio (OR), 1.84; 97.5 % Confidence Interval (CI), 1.04-3.26) in the adjusted intention-to-treat analysis. Those in the VR group had higher CAR at weeks 5-22 (OR, 2.01; CI, 1.20-3.36) than those in the NRT group. Results with 7PP revealed that both NRT+ (OR, 1.72; CI, 1.04-2.85) and VR (OR, 1.96; CI, 1.20-3.23) were more effective than NRT at 22 weeks. As compared to NRT monotherapy, NRT+ and VR produced significant increases in CAR for weeks 5-10 (OR, 1.52; CI, 1.00-2.30 and OR, 1.58; CI, 1.04-2.39, respectively); results were similar, but somewhat stronger, when 7PP was used at 10 weeks (OR, 1.57; CI, 1.03-2.41 and OR, 1.79; CI, 1.17-2.73, respectively). All medications were well tolerated, but participants in the VR group experienced more fatigue, digestive symptoms (e.g., nausea, diarrhea), and sleep-related concerns (e.g., abnormal dreams, insomnia), but less dermatologic symptoms than those in the NRT or NRT+ groups. The frequency of serious adverse events did not differ between groups.\u2026", "author" : [ { "dropping-particle" : "", "family" : "Tulloch", "given" : "Heather E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pipe", "given" : "Andrew L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Els", "given" : "Charl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clyde", "given" : "Matthew J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reid", "given" : "Robert D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMC medicine", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2016", "6", "7" ] ] }, "note" : "NULL", "page" : "80", "title" : "Flexible, dual-form nicotine replacement therapy or varenicline in comparison with nicotine patch for smoking cessation: a randomized controlled trial.", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(155)", "plainTextFormattedCitation" : "(155)", "previouslyFormattedCitation" : "(155)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(155). Varenicline can also help with cravings and reduction in overall alcohol consumption in someADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1177/1060028014545806", "ISSN" : "1542-6270", "PMID" : "25095786", "abstract" : "OBJECTIVE To summarize the efficacy and safety data for the use of varenicline in the treatment of alcohol use disorders. DATA SOURCES A literature search was conducted in PubMed, International Pharmaceutical Abstracts, and Cochrane Library (through May 2014). Key search terms included varenicline, alcohol, alcohol dependence, alcoholism, ethanol, and nicotinic acetylcholine receptor. Additional references were identified from literature citations. STUDY SELECTION AND DATA EXTRACTION Results were limited to clinical trials and case reports that discussed either the use of varenicline in alcohol drinking patients or adverse effects experienced with its use. Only English language studies in humans were reviewed. DATA SYNTHESIS In all, 7 randomized, placebo-controlled clinical trials and 1 open-label study were identified that evaluated the impact of varenicline on various drinking-related end points. The studies were conducted in patients dependent on alcohol (n=4), non-alcohol-dependent patients (n=3), and patients with a history of alcohol dependence but who had been abstinent for at least 6 months (n=1). The majority of the studies classified their participants as heavy drinkers; however, this definition varied across studies. Most studies included smokers, but 2 trials included both smokers and nonsmokers. CONCLUSIONS Evidence supports the use of varenicline for the reduction of alcohol craving as well as for the reduction of overall alcohol consumption in patients with alcohol use disorders. However, it is not likely to improve abstinence rates. Although most of the data were derived from patients with concurrent nicotine dependence, the effects of varenicline appear to occur independent of baseline smoking status.", "author" : [ { "dropping-particle" : "", "family" : "Erwin", "given" : "Beth L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slaton", "given" : "Rachel M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Annals of pharmacotherapy", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2014", "11" ] ] }, "note" : "NULL", "page" : "1445-55", "title" : "Varenicline in the treatment of alcohol use disorders.", "type" : "article-journal", "volume" : "48" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(156)", "plainTextFormattedCitation" : "(156)", "previouslyFormattedCitation" : "(156)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(156) but not allADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/acer.12854", "ISSN" : "1530-0277", "PMID" : "26414337", "abstract" : "BACKGROUND Alcohol dependence is a devastating illness affecting a large population, and new pharmacological treatments with good efficacy are greatly needed. One potential candidate is varenicline, a smoking cessation agent with partial agonist action at \u03b14 \u03b22 nicotinic acetylcholine receptors. METHODS A total of 160 subjects, 30 to 70 years of age, fulfilling DSM-IV criteria for alcohol dependence without any serious physical or mental disorders, were recruited through advertisement at 3 university clinics in Sweden during March 2009 to January 2011. After a 2-week placebo run-in period, subjects received 2 mg varenicline daily (titrated from 0.5 mg during first week) or placebo for 12 weeks in a double-blind manner. RESULTS The primary outcome was the proportion of heavy drinking days, measured by self-reported alcohol consumption. Primary and secondary outcomes were calculated as a mean over the 10-week steady-state active treatment period. In the primary outcome analysis, no effect of varenicline over placebo was found (p = 0.73 for the intention to treat [ITT] and 0.92 for per protocol [PP]). Secondary outcome analysis found a significant reduction of specific alcohol marker phosphatidylethanol (PEth) in the blood in the varenicline group compared to placebo (p = 0.02 ITT). Craving (p = 0.048 PP) and Alcohol Use Disorders Identification Test (AUDIT) scores (p = 0.015 ITT) were also reduced in the active treatment group. PEth more strongly correlated with self-reported alcohol consumption than carbohydrate-deficient ttransferrin and \u03b3-glutamyl transferase, and correlation coefficients were higher in the varenicline group than in the placebo group for all markers. CONCLUSIONS Although the results of the main outcome of this study did not support an effect of varenicline in alcohol-dependent individuals, the secondary analyses of PEth, craving and AUDIT score support an effect of varenicline on alcohol consumption. The disclosure of a treatment effect and the lack of a clear placebo effect when using PEth as outcome variable, together with a nonsymmetric bias associated with self-reported data, strongly argue for using the specific biomarker PEth in studies of treatments of alcohol dependence.", "author" : [ { "dropping-particle" : "", "family" : "Bejczy", "given" : "Andrea", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "L\u00f6f", "given" : "Elin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walther", "given" : "Lisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guterstam", "given" : "Joar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hammarberg", "given" : "Anders", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Asanovska", "given" : "Gulber", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franck", "given" : "Johan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Isaksson", "given" : "Anders", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "S\u00f6derpalm", "given" : "Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Alcoholism, clinical and experimental research", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2015", "11" ] ] }, "note" : "NULL", "page" : "2189-99", "title" : "Varenicline for treatment of alcohol dependence: a randomized, placebo-controlled trial.", "type" : "article-journal", "volume" : "39" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(157)", "plainTextFormattedCitation" : "(157)", "previouslyFormattedCitation" : "(157)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(157) studies and thus can be an option for patients with both alcohol and tobacco addiction. A recent systematic review supported the combination of bupropion and varenicline for greater efficacy than varenicline monotherapy for smoking cessationADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3109/00952990.2015.1117480", "ISSN" : "1097-9891", "PMID" : "26809272", "abstract" : "BACKGROUND Tobacco is the leading cause of preventable death in the world. Current cessation medications include nicotine replacement therapy (NRT), varenicline, and bupropion, while combination therapy primarily entails NRT with either varenicline or bupropion. However, recent studies have examined varenicline and bupropion in combination. OBJECTIVES A systematic review assessing the efficacy and safety of combination varenicline and bupropion was conducted. METHODS PubMed and were searched using terms: \"varenicline combination\", \"bupropion combination\", \"bupropion AND varenicline\", and \"bupropion AND varenicline combination smoking cessation\", yielding four studies including 1193 total patients. RESULTS Combination therapy yielded greater efficacy than varenicline monotherapy in two randomized controlled trials and one retrospective outcomes study. One single-arm Phase II trial provided additional efficacy and safety data. Of the prospective trials, one displayed a greater 4-week smoking abstinence for weeks 8-11 with combination (39.8%) versus monotherapy (25.9%) (OR = 1.89; 95% CI = 1.07-3.35). The other demonstrated greater prolonged abstinence (continuous abstinence from week 2) at 12 weeks (OR = 1.49; 95% CI = 1.05-2.12) and 26 weeks (OR = 1.52; 95% CI = 1.04-2.22), though results were not significant at 52 weeks in this study. The retrospective study displayed higher success rates (continuous abstinence rates at 52 weeks) with combination varenicline and bupropion (55.0%; compared to varenicline monotherapy (32.1%), p < 0.001). Subgroup analyses suggest that this combination may be more beneficial in males and patients with higher baseline nicotine dependence. CONCLUSION To the authors' knowledge, this is the first review conducted to compile current literature on this novel pharmacotherapy combination for smoking cessation. Combination bupropion SR and varenicline displayed greater efficacy in smoking cessation than varenicline monotherapy, though further safety analysis is warranted to rule out additive psychiatric adverse effects.", "author" : [ { "dropping-particle" : "", "family" : "Vogeler", "given" : "Tiffany", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McClain", "given" : "Claire", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Evoy", "given" : "Kirk E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American journal of drug and alcohol abuse", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2016", "3", "3" ] ] }, "note" : "NULL", "page" : "129-39", "title" : "Combination bupropion SR and varenicline for smoking cessation: a systematic review.", "type" : "article-journal", "volume" : "42" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(158)", "plainTextFormattedCitation" : "(158)", "previouslyFormattedCitation" : "(158)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(158). Clonidine and nortriptyline are considered second line symptoms to reduce nicotine withdrawal as the results are inconsistent. In a review of Cochrane reviews of pharmacotherapy for smoking cessation through 2012, 267 studies involving 101,804 participants were identifiedADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/14651858.CD009329.pub2", "ISSN" : "1469-493X", "PMID" : "23728690", "abstract" : "BACKGROUND Smoking is the leading preventable cause of illness and premature death worldwide. Some medications have been proven to help people to quit, with three licensed for this purpose in Europe and the USA: nicotine replacement therapy (NRT), bupropion, and varenicline. Cytisine (a treatment pharmacologically similar to varenicline) is also licensed for use in Russia and some of the former socialist economy countries. Other therapies, including nortriptyline, have also been tested for effectiveness. OBJECTIVES How do NRT, bupropion and varenicline compare with placebo and with each other in achieving long-term abstinence (six months or longer)? How do the remaining treatments compare with placebo in achieving long-term abstinence? How do the risks of adverse and serious adverse events (SAEs) compare between the treatments, and are there instances where the harms may outweigh the benefits? METHODS The overview is restricted to Cochrane reviews, all of which include randomised trials. Participants are usually adult smokers, but we exclude reviews of smoking cessation for pregnant women and in particular disease groups or specific settings. We cover nicotine replacement therapy (NRT), antidepressants (bupropion and nortriptyline), nicotine receptor partial agonists (varenicline and cytisine), anxiolytics, selective type 1 cannabinoid receptor antagonists (rimonabant), clonidine, lobeline, dianicline, mecamylamine, Nicobrevin, opioid antagonists, nicotine vaccines, and silver acetate. Our outcome for benefit is continuous or prolonged abstinence at least six months from the start of treatment. Our outcome for harms is the incidence of serious adverse events associated with each of the treatments. We searched the Cochrane Database of Systematic Reviews (CDSR) in The Cochrane Library, for any reviews with 'smoking' in the title, abstract or keyword fields. The last search was conducted in November 2012. We assessed methodological quality using a revised version of the AMSTAR scale. For NRT, bupropion and varenicline we conducted network meta-analyses, comparing each with the others and with placebo for benefit, and varenicline and bupropion for risks of serious adverse events. MAIN RESULTS We identified 12 treatment-specific reviews. The analyses covered 267 studies, involving 101,804 participants. Both NRT and bupropion were superior to placebo (odds ratios (OR) 1.84; 95% credible interval (CredI) 1.71 to 1.99, and 1.82; 95% CredI 1.60 to 2.06 respectiv\u2026", "author" : [ { "dropping-particle" : "", "family" : "Cahill", "given" : "Kate", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stevens", "given" : "Sarah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perera", "given" : "Rafael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lancaster", "given" : "Tim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Cochrane database of systematic reviews", "editor" : [ { "dropping-particle" : "", "family" : "Cahill", "given" : "Kate", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2013", "5", "31" ] ] }, "note" : "NULL", "page" : "CD009329", "publisher" : "John Wiley & Sons, Ltd", "publisher-place" : "Chichester, UK", "title" : "Pharmacological interventions for smoking cessation: an overview and network meta-analysis.", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(159)", "plainTextFormattedCitation" : "(159)", "previouslyFormattedCitation" : "(159)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(159). Nicotine replacement, bupropion, varenicline, and cytisine, another partial nicotine receptor agonist, had the greatest evidence for improving the chances of quitting. Non-pharmacological treatment: Cognitive behavioral therapy (CBT) combined with smoking cessation medications can be effective in smokers who are motivated to quitADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jsat.2012.12.004", "ISSN" : "1873-6483", "PMID" : "23312770", "abstract" : "We examined the role of sexual gender, age, working status, education, cigarettes per day, Fagerstr\u00f6m test, age of onset, pharmacologic intervention (bupropion or varenicline), 10 sessions of cognitive-behavioral group counseling therapy (GCT) conducted over 6 weeks, and level of attendance of the counseling program as predictors of smoking cessation on 1282 Italian adult smokers. Results of a multi-variate forward stepwise conditional logistic analysis, at the first step, indicate that subjects who attended the program from 4 to 6 sessions and from 1 to 3 sessions, respectively, resulted about 3 times and 24 times more likely to smoke than those attending from 7 to 10 sessions; at the second step, subjects with high Fagerstr\u00f6m score were 2 times more likely to smoke than subjects with low/middle Fagerstr\u00f6m; at the third step, subjects treated only with GCT were 2 times more likely to smoke than subjects with combined pharmacologic interventions and GCT; at the fourth step, subjects with age of onset less than 17 years were 1.5 times more likely to smoke than subjects with a higher age of onset; eventually, at the fifth step women resulted 1.5 times more likely to smoke than men. In conclusion, we found that a steady attendance of the cognitive behavioral program, as well as the addition of pharmacologic interventions to counseling, remarkably increased the probability of the smoking cessation behavior to be determined. Nevertheless, FTQ was a valid measure in predicting the smoking cessation, and women revealed to be more likely to keep the smoking behavior, as well as subjects who declared an age of onset less than 17 years.", "author" : [ { "dropping-particle" : "", "family" : "Iliceto", "given" : "Paolo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fino", "given" : "Emanuele", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pasquariello", "given" : "Stefania", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "D'Angelo Di Paola", "given" : "Maria E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Enea", "given" : "Domenico", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of substance abuse treatment", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2013", "5" ] ] }, "note" : "NULL", "page" : "534-40", "title" : "Predictors of success in smoking cessation among Italian adults motivated to quit.", "type" : "article-journal", "volume" : "44" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(160)", "plainTextFormattedCitation" : "(160)", "previouslyFormattedCitation" : "(160)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(160). Mindfulness-based therapy may help with recovery from smoking relapseADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1037/ccp0000117", "ISSN" : "1939-2117", "PMID" : "27213492", "abstract" : "OBJECTIVE To compare the efficacy of Mindfulness-Based Addiction Treatment (MBAT) to a Cognitive Behavioral Treatment (CBT) that matched MBAT on treatment contact time, and a Usual Care (UC) condition that comprised brief individual counseling. METHOD Participants (N = 412) were 48.2% African American, 41.5% non-Latino White, 5.4% Latino, and 4.9% other, and 57.6% reported a total annual household income < $30,000. The majority of participants were female (54.9%). Mean cigarettes per day was 19.9 (SD = 10.1). Following the baseline visit, participants were randomized to UC (n = 103), CBT (n = 155), or MBAT (n = 154). All participants were given self-help materials and nicotine patch therapy. CBT and MBAT groups received 8 2-hr in-person group counseling sessions. UC participants received 4 brief individual counseling sessions. Biochemically verified smoking abstinence was assessed 4 and 26 weeks after the quit date. RESULTS Logistic random effects model analyses over time indicated no overall significant treatment effects (completers only: F(2, 236) = 0.29, p = .749; intent-to-treat: F(2, 401) = 0.9, p = .407). Among participants classified as smoking at the last treatment session, analyses examining the recovery of abstinence revealed a significant overall treatment effect, F(2, 103) = 4.41, p = .015 (MBAT vs. CBT: OR = 4.94, 95% CI: 1.47 to 16.59, p = .010, Effect Size = .88; MBAT vs. UC: OR = 4.18, 95% CI: 1.04 to 16.75, p = .043, Effect Size = .79). CONCLUSION Although there were no overall significant effects of treatment on abstinence, MBAT may be more effective than CBT or UC in promoting recovery from lapses. (PsycINFO Database Record", "author" : [ { "dropping-particle" : "", "family" : "Vidrine", "given" : "Jennifer Irvin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spears", "given" : "Claire Adams", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heppner", "given" : "Whitney L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reitzel", "given" : "Lorraine R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marcus", "given" : "Marianne T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cinciripini", "given" : "Paul M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waters", "given" : "Andrew J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Yisheng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nguyen", "given" : "Nga Thi To", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cao", "given" : "Yumei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tindle", "given" : "Hilary A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fine", "given" : "Micki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Safranek", "given" : "Linda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wetter", "given" : "David W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of consulting and clinical psychology", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2016", "9" ] ] }, "note" : "NULL", "page" : "824-838", "title" : "Efficacy of mindfulness-based addiction treatment (MBAT) for smoking cessation and lapse recovery: A randomized clinical trial.", "type" : "article-journal", "volume" : "84" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(161)", "plainTextFormattedCitation" : "(161)", "previouslyFormattedCitation" : "(161)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(161). Other behavioral interventions that have shown promise are self-help groups, hypnosis, and motivational interviewing techniques delivered by trained behavioral specialistsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/jhm.2093", "ISSN" : "1553-5606", "PMID" : "24167011", "abstract" : "BACKGROUND Burnout is a syndrome affecting the entirety of work life and characterized by cynicism, detachment, and inefficacy. Despite longstanding concerns about burnout in hospital medicine, few data about burnout in hospitalists have been published. PURPOSE A systematic review of the literature on burnout in inpatient-based and outpatient-based physicians worldwide was undertaken to determine whether inpatient physicians experience more burnout than outpatient physicians. DATA SOURCES Five medical databases were searched for relevant terms with no language restrictions. Authors were contacted for unpublished data and clarification of the practice location of study subjects. STUDY SELECTION Two investigators independently reviewed each article. Included studies provided a measure of burnout in inpatient and/or outpatient nontrainee physicians. DATA EXTRACTION Fifty-four studies met inclusion criteria, 15 of which provided direct comparisons of inpatient and outpatient physicians. Twenty-eight studies used the same burnout measure and therefore were amenable to statistical analysis. DATA SYNTHESIS Outpatient physicians reported more emotional exhaustion than inpatient physicians. No statistically significant differences in depersonalization or personal accomplishment were found. Further comparisons were limited by the heterogeneity of instruments used to measure burnout and the lack of available information about practice location in many studies. CONCLUSIONS The existing literature does not support the widely held belief that burnout is more frequent in hospitalists than outpatient physicians. Better comparative studies of hospitalist burnout are needed.", "author" : [ { "dropping-particle" : "", "family" : "Roberts", "given" : "Daniel L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cannon", "given" : "Keith J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wellik", "given" : "Kay E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Qing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Budavari", "given" : "Adriane I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of hospital medicine", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2013", "11" ] ] }, "note" : "NULL", "page" : "653-64", "title" : "Burnout in inpatient-based versus outpatient-based physicians: a systematic review and meta-analysis.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(162)", "plainTextFormattedCitation" : "(162)", "previouslyFormattedCitation" : "(162)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(162). Pramod Kumar Garg & Eva Szigethy Q5.?Do enzymes and antioxidants influence pain in CP??Pancreatic enzyme therapy with high protease content may be tried as an initial treatment for pain relief in patients with CP. Furthermore; combination of antioxidants in sufficient dosages should be included in the armamentarium of pain treatments (Quality assessment: moderate; Recommendation: strong; Agreement: weak) Role of Pancreatic Enzyme Supplementation on Pain Relief in Chronic PancreatitisPancreatic enzymes have been used for relief of pain in patients with chronic pancreatitis (CP). The pathophysiological basis of using pancreatic enzymes is related to a possible negative feedback loop involving cholecystokinin that regulates pancreatic exocrine secretion ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1172/JCI112534", "ISSN" : "0021-9738", "PMID" : "3711342", "abstract" : "Feedback regulation of pancreatic enzyme secretion occurs in rats. Whether such a system exists in man remains unsettled and the responsible mechanism is unknown. To investigate this question gastrointestinal intubation and perfusion were performed in 12 healthy subjects. Intraduodenal perfusion of trypsin-inhibited phenylalanine-, oleic acid-, and meal-stimulated chymotrypsin and lipase outputs in a dose-related manner. The minimal concentration of bovine trypsin needed to inhibit pancreatic enzyme secretion was 0.5 g/liter. 1 g/liter caused a maximal suppression of 35 +/- 4% of the phenylalanine-stimulated chymotrypsin release. This inhibitory effect was protease-specific. Intraduodenal perfusion of phenylalanine and oleic acid increased plasma cholecystokinin (CCK) from a basal level of 0.9 +/- 0.06 to 5.3 +/- 0.9 pM and 7.2 +/- 1.3 pM, respectively. Addition of bovine trypsin to the perfusates significantly reduced the plasma CCK level to basal values. This inhibitory effect of trypsin on CCK release was dose dependent and specific to proteases. Therefore, the present studies indicate that feedback regulation of pancreatic enzyme secretion is operative in man and it is mediated by release of CCK.", "author" : [ { "dropping-particle" : "", "family" : "Owyang", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Louie", "given" : "D S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tatum", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of clinical investigation", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "1986", "6", "1" ] ] }, "note" : "NULL", "page" : "2042-7", "title" : "Feedback regulation of pancreatic enzyme secretion. Suppression of cholecystokinin release by trypsin.", "type" : "article-journal", "volume" : "77" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(163)", "plainTextFormattedCitation" : "(163)", "previouslyFormattedCitation" : "(163)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(163). Intraduodenal infusion of trypsin decreases pancreatic exocrine secretion through suppression of cholecystokinin (CCK)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0017-5749", "PMID" : "2767512", "abstract" : "We have evaluated the effects of porcine pancreatic extracts on human pancreatic secretion. Ten male volunteers were intubated with a 4-lumen jejunal tube to collect gastric and duodenal secretions separately via the first and third tube, to infuse PEG 4000 distal the pylorus via the second tube and to apply porcine pancreatic extracts via the fourth tube distal the ligament of Treitz. Pancreatic extracts were given four times at 40 minute intervals; the first two as active enzymes and subsequently as heat denatured proportions. Secretin was continuously infused intravenously (0.5 E/kg bw/h) to achieve minimal pancreatic flow. Lipase, amylase, trypsin, chymotrypsin, volume, and bicarbonate were measured in duodenal contents in eight pooled 15 minute fractions. Three subjects who received HEPES-Ringer buffer instead of pancreatic enzymes served as controls. Plasma cholecystokinin (CCK) was measured using a sensitive bioassay. Both active and heat denatured pancreatic extracts caused a small but significant increase in amylase and chymotrypsin secretion. Basal plasma CCK values were 0.85 (0.05) pM. After intrajejunal instillation of either active or heat denatured pancreatic extracts plasma CCK rose to 3.25 (0.30) pM and to 3.28 (0.36) pM respectively. In a second group of five volunteers, plasma CCK concentrations were measured after a test meal. On day 1, volunteers received a liquid fat and protein rich meal and on day 2, the same test meal containing porcine pancreatic extracts. In both cases, a similar increase in plasma CCK was observed. We conclude that therapy with pancreatic extracts stimulate pancreatic enzyme secretion. This may be mediated through release of CCK.", "author" : [ { "dropping-particle" : "", "family" : "M\u00f6ssner", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wresky", "given" : "H P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kestel", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zeeh", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Regner", "given" : "U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fischbach", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gut", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "1989", "8" ] ] }, "note" : "NULL", "page" : "1143-9", "title" : "Influence of treatment with pancreatic extracts on pancreatic enzyme secretion.", "type" : "article-journal", "volume" : "30" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0022-2143", "PMID" : "7350238", "abstract" : "Feedback inhibition of basal pancreatic enzyme secretion by luminal pancreatic enzymes appears to be an important regulator of pancreatic secretion in some laboratory animals. To determine whether pancreatic enzymes in the jejunum influence pancreatic or gastric functions in healthy man, we intubated six subjects with a gastric sump tube and a four-lumen duodenal tube which provided (1) a duodenal perfusion site, (2) a duodenal aspiration site, (3) an inflatable balloon immediately distal to the aspiration site, and (4) a jejunal perfusion site immediately beyond the balloon. In this way, the gastroduodenal segment could be functionally separated from the remainder of the intestine. The jejunum was exposed to normal saline, active pancreatic-biliary secretions, or pancreatic-biliary secretions in which the enzymes had been inactivated by heat. Ten minutes after initiation of each jejunal perfusion, normal saline was instilled into the stomach. No differences in trypsin secretion, gastric acid secretion, or gastric emptying occurred with the different jejunal perfusates. We therefore conclude that normal man, in the absence of intraluminal nutrients, does not exhibit a jejunal pancreatic enzyme-dependent feedback control mechanism for pancreatic enzyme or gastric secretion. However, our study does not exclude the possibility of a duodenal feedback regulatory mechanism.", "author" : [ { "dropping-particle" : "", "family" : "Krawisz", "given" : "B R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miller", "given" : "L J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "DiMagno", "given" : "E P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Go", "given" : "V L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of laboratory and clinical medicine", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "1980", "1" ] ] }, "note" : "NULL", "page" : "13-8", "title" : "In the absence of nutrients, pancreatic-biliary secretions in the jejunum do not exert feedback control of human pancreatic or gastric function.", "type" : "article-journal", "volume" : "95" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(164,165)", "plainTextFormattedCitation" : "(164,165)", "previouslyFormattedCitation" : "(164,165)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(164,165), but other studies have not shown that such a negative feedback mechanism operates. It is believed that nutrients stimulate release of cholecystokinin releasing factor (CRF) from the duodenum upon physiological delivery of chyme into the duodenum. The CRF releases cholecystokinin, which stimulates pancreatic secretion. Theoretically, the pancreatic enzymes degrade CRF thus limiting the release of cholecystokinin and subsequently decrease pancreatic secretion completing a negative feedback loop. A reduction in pancreatic enzymes in patients with CP therefore increases cholecystokinin release and pancreatic secretion. This may increase intraductal pressure in patients with CP who have ductal obstruction due to calculi or stricture and contributes to pain. Thus, the rationale of giving pancreatic enzymes for pain relief is that adequate enzymes will degrade CRF, decrease cholecystokinin release and thus reduce pancreatic secretion. There are many concerns with such a hypothesis. First, the negative feedback loop is not fully understood well or confirmed. Second, increased pancreatic secretion in patients with CP is counterintuitive because there is significant functional impairment in them. Third, increased intraductal pressure is but one of the mechanisms of pancreatic pain and not widely accepted. Fourth, enzyme supplementation has not been conclusively shown to decrease pancreatic secretion and reduce intraductal pressure as hypothesized. Six randomized clinical trials (RCTs) have been reported on the effect of pancreatic enzymes in pain relief. In a review of theseADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0016-5085", "PMID" : "9721175", "author" : [ { "dropping-particle" : "", "family" : "Warshaw", "given" : "A L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banks", "given" : "P A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fern\u00e1ndez-Del Castillo", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "1998", "9" ] ] }, "note" : "NULL", "page" : "765-76", "title" : "AGA technical review: treatment of pain in chronic pancreatitis.", "type" : "article-journal", "volume" : "115" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(166)", "plainTextFormattedCitation" : "(166)", "previouslyFormattedCitation" : "(166)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(166), pain relief using pancreatic enzymes as tablets was noted in two trialsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0016-5085", "PMID" : "6202586", "abstract" : "The purposes of this study were to (a) evaluate the effect of pancreatic extract administered to patients with chronic pancreatitis and recurrent abdominal pain in a placebo-controlled, double-blind crossover study, (b) investigate the effects of acute intraduodenal pancreatic enzyme perfusion on pancreatic secretion, and (c) assess the effect of chronic, noninterrupted pancreatic extract administration on basal and stimulated pancreatic secretion. These studies demonstrated that pancreatic extract decreases abdominal pain and that intraduodenal perfusion with proteases but not with amylase or lipase suppresses pancreatic exocrine secretion in patients with chronic pancreatitis. Chronic administration of pancreatic extract to patients with chronic pancreatitis decreased both basal and stimulated pancreatic exocrine secretion.", "author" : [ { "dropping-particle" : "", "family" : "Slaff", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jacobson", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tillman", "given" : "C R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Curington", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Toskes", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "1984", "7" ] ] }, "note" : "NULL", "page" : "44-52", "title" : "Protease-specific suppression of pancreatic exocrine secretion.", "type" : "article-journal", "volume" : "87" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0012-2823", "PMID" : "9832631", "abstract" : "The traditional ductal model for the development of chronic pancreatitis leaves many questions unanswered and it has not facilitated management. An alternate philosophy centres on the acinar cell as the site of mounting oxidant stress, usually as a result of steady exposure to xenobiotics that induce cytochrome P450 mono-oxygenases while depleting glutathione: ductal changes are regarded as secondary, disease-compounding manifestations of the oxidant environment. Within this framework each burst of oxidant stress jeopardises exocytosis, to trigger an attack of pancreatitis by interfering with the methionine-to-glutathione transsulphuration pathway, which interacts closely with ascorbate and selenium. The resulting diversion of free radical oxidation products into the pancreatic interstitium causes mast cells to degranulate, thereby provoking inflammation, the activation of nociceptive axon reflexes, and profibrotic interactions.", "author" : [ { "dropping-particle" : "", "family" : "Braganza", "given" : "J M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Digestion", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "1998" ] ] }, "note" : "NULL", "page" : "1-12", "title" : "A framework for the aetiogenesis of chronic pancreatitis.", "type" : "article-journal", "volume" : "59 Suppl 4" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(167,168)", "plainTextFormattedCitation" : "(167,168)", "previouslyFormattedCitation" : "(167,168)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(167,168) and no benefit was noted in 4 trials that used acid-protected capsule forms of enzyme replacementADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0036-5521", "PMID" : "3633631", "abstract" : "The symptomatic effect of pancreatic enzyme substitution therapy was examined in a 4-week double-blind crossover study. Twenty patients, 11 with and 9 without steatorrhoea, were examined. Pancreatic steatorrhoea was reduced from a median of 24 g/day to 10 g/day by the enzyme therapy (P less than 0.01). No significant pain reduction was found in either of the two groups, although there was a tendency to reduction in pain and analgetic consumption in the patients with steatorrhoea when treated with pancreatic enzymes. It is concluded that pancreatic steatorrhoea is still the only indication for pancreatic enzyme therapy.", "author" : [ { "dropping-particle" : "", "family" : "Halgreen", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "N T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Worning", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of gastroenterology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "1986", "1" ] ] }, "note" : "NULL", "page" : "104-8", "title" : "Symptomatic effect of pancreatic enzyme therapy in patients with chronic pancreatitis.", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0012-2823", "PMID" : "1289173", "abstract" : "According to the theory of negative feedback regulation of pancreatic enzyme secretion by proteases, treatment with pancreatic extracts has been proposed to lower pain in chronic pancreatitis by decreasing pancreatic duct pressure. We conducted a prospective placebo-controlled double blind multicenter study to investigate the effect of porcine pancreatic extracts on pain in chronic pancreatitis. 47 patients with pain (41 males, 6 females) due to chronic pancreatitis documented by sonography, endoscopic retrograde cholangiopancreatography, and CT were included. Exclusion criteria were steatorrhea above 30 g/day, gastric or pancreatic resections in the history, and serum bilirubin above 1.5 mg/dl. Patients received pancreatic extracts (acid-protected microtablets; Panzytrat -20,000; 5 x 2 capsules/day; proteases/capsule 1,000 Pharmacopoea europaea units) for 14 days followed by treatment with placebo for another 14 days or vice versa. Pain (graded from 0 to 3) and concomitant use of analgesics (N-butylscopolaminiumbromide and tramadol) were recorded by diary. Physical examination and blood chemistry were done at day -1, 15 and 29. Quantitative stool fat was determined at days -2/-1, 13/14 and 27/28. 43 patients completed the studies. Pain improved in most patients irrespective of whether they started with placebo or verum. There was no significant difference between both treatment arms. We conclude that pancreatic extracts are not very efficient in lowering pain.", "author" : [ { "dropping-particle" : "", "family" : "M\u00f6ssner", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Secknus", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyer", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Niederau", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adler", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Digestion", "id" : "ITEM-2", "issue" : "1-2", "issued" : { "date-parts" : [ [ "1992" ] ] }, "note" : "NULL", "page" : "54-66", "title" : "Treatment of pain with pancreatic extracts in chronic pancreatitis: results of a prospective placebo-controlled multicenter trial.", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISSN" : "0036-5521", "PMID" : "7610357", "abstract" : "BACKGROUND This study was aimed to investigate the effect of long-term treatment with high-protease pancreatic extract on the recurrent abdominal pain of patients with chronic pancreatitis. METHODS Twenty-six patients with a firm diagnosis of chronic pancreatitis and a pattern of recurrent pain were recruited and randomly assigned to treatment with pancreatic extract (Pancrex-Duo capsules, each containing 34,375 USP units of protease in enteric-coated microspheres) or placebo, at a dose of four capsules four times daily, for 4 months. At the end of the first period patients were switched to the other medication for the next 4 months. Four patients did not complete the study because of unbearable recurring pain or inadequate compliance with treatment. The other 22 patients daily recorded the presence, intensity, and duration of pain and the consumption of analgesics, for 8 months. RESULTS No difference was found when intraindividual records during placebo and extract treatment periods were compared. Conversely, in the second 4 months of follow-up, regardless of the treatment given in the first period, there was a significant reduction in the cumulative pain score (median, 95; range, 0-1005, versus 134; 0-972; p < 0.05), in the number of days (8; 0-132, versus 13; 0-126; p < 0.02) and hours (54; 0-680, versus 80; 0-602; p < 0.05) of pain, and in the analgesic consumption score (0; 0-22, versus 12; 0-44; p = 0.02). CONCLUSIONS Chronic supplementation with pancreatic extract is not beneficial in the management of recurrent pain in patients with chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Malesci", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gaia", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fioretta", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bocchia", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ciravegna", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cantor", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vantini", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of gastroenterology", "id" : "ITEM-3", "issue" : "4", "issued" : { "date-parts" : [ [ "1995", "4" ] ] }, "note" : "NULL", "page" : "392-8", "title" : "No effect of long-term treatment with pancreatic extract on recurrent abdominal pain in patients with chronic pancreatitis.", "type" : "article-journal", "volume" : "30" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "larvin M,McMohan MJ, Thomas WEG", "given" : "Puntis MCA.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-4", "issue" : "100", "issued" : { "date-parts" : [ [ "1991" ] ] }, "page" : "A283", "title" : "Creon (enteric coated pancreatin microspheres) for the treatment of pain in chronic pancreatitis: a double-blind randomised placebo-controlled crossover study", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(169\u2013172)", "plainTextFormattedCitation" : "(169\u2013172)", "previouslyFormattedCitation" : "(169\u2013172)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(169–172). The reason could be that the acid-protected form of pancreatic enzymes was not released in the duodenum and, therefore, could not activate the proposed negative feedback mechanism. Pancreatic enzyme supplements have shown most benefit for patients with small pancreatic duct disease, idiopathic pancreatitis and among women. These trials were conducted in 1980s and 1990s and have had certain methodological issues such as small sample size, heterogeneous patient population, variability in enzyme preparations, differences in outcome measures, and lack of standardized pain measuring tools. Despite these concerns, pancreatic enzymes are widely prescribed to patients with CP in the hope that at least some benefit may be derived. If enzyme therapy is tried in clinical practice as an initial treatment modality, the preparations of pancreatic enzymes should be uncoated, contain large amounts of proteases (>25,000 USP units per tablet) and be given in a dosage of four to eight tablets four times a day. In addition to the negative feedback regulation of pancreatic secretion, the other putative benefits of enzymes are – (i) better digestion of food leading to physiological ileal brake and help to regain intestinal motility as the ileal brake is a regulatory physiological feedback mediated by delivery of nutrients into the distal ileum, which inhibits gastric emptying and proximal small intestinal motilityADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0017-5749", "PMID" : "6706215", "abstract" : "The possibility that malabsorbed fat passing through the human ileum exerts an inhibitory feedback control on jejunal motility has been investigated in 24 normal subjects by perfusing the ileum with a fat containing solution designed to produce ileal luminal fat concentrations similar to those in steatorrhoea (30-40 mg/ml). Mean transit times through a 30 cm saline perfused jejunal segment were measured by a dye dilution technique. Thirty minutes after ileal fat perfusion, mean transit times rose markedly to 18.9 +/- 2.5 minutes from a control value of 7.5 +/- 0.9 minutes (n = 5; p less than 0.05). This was associated with an increase in volume of the perfused segment which rose to 175.1 +/- 22.9 ml (control 97.6 +/- 10.3 ml, n = 5; p less than 0.05). Transit times and segmental volumes had returned towards basal values 90 minutes after completing the fat perfusion. Further studies showed that ileal fat perfusion produced a pronounced inhibition of jejunal pressure wave activity, percentage duration of activity falling from a control level of 40.3 +/- 5.0% to 14.9 +/- 2.8% in the hour after ileal perfusion (p less than 0.01). Ileal fat perfusion was associated with marked rises in plasma enteroglucagon and neurotensin, the peak values (218 +/- 37 and 68 +/- 13.1 pmol/l) being comparable with those observed postprandially in coeliac disease. These observations show the existence in man of an inhibitory intestinal control mechanism, whereby ileal fat perfusion inhibits jejunal motility and delays caudal transit of jejunal contents.", "author" : [ { "dropping-particle" : "", "family" : "Spiller", "given" : "R C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trotman", "given" : "I F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Higgins", "given" : "B E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghatei", "given" : "M A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grimble", "given" : "G K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Y C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bloom", "given" : "S R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Misiewicz", "given" : "J J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silk", "given" : "D B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gut", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "1984", "4" ] ] }, "note" : "NULL", "page" : "365-74", "title" : "The ileal brake--inhibition of jejunal motility after ileal fat perfusion in man.", "type" : "article-journal", "volume" : "25" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0016-5085", "PMID" : "6690354", "abstract" : "The small bowel transit time of 100 ml of lactulose solution infused at the ligament of Treitz was measured by breath hydrogen excretion in paired studies carried out in 43 healthy volunteers during infusion (1.2 ml/min) of equal volumes (100 ml) of isotonic solutions of either fat emulsion (Intralipid, Prosparol, or Calogen), protein hydrolysate, glucose, or saline into either the jejunum (90 cm from the teeth), ileum (205 cm from the teeth), or colon (350 or 400 cm from the teeth). Ileal infusion of Intralipid or protein hydrolysate resulted in significant delays in small bowel transit time (125 +/- 21 min and 71 +/- 11 min, respectively) compared with infusion of saline (50 +/- 3 min; p less than 0.02 and p less than 0.05). These delays were not associated with any significant alteration in plasma levels of neurotensin or enteroglucagon. Small bowel transit time was unaffected by infusion of nutrients into the colon or jejunum, although jejunal infusion of Intralipid increased the plasma levels of enteroglucagon and neurotensin (p less than 0.01 and p less than 0.02, respectively) after the start of lactulose infusion. In a separate series of paired experiments, infusion of Intralipid into the ileum in 5 volunteers significantly delayed the transit of a solid test meal labeled with 25 microCi of 99mTc-sulfur colloid through both the stomach and small intestine. These data support the existence of a mechanism whereby the presence of unabsorbed food in the ileum may enhance absorption by delaying the passage of food through the small intestine.", "author" : [ { "dropping-particle" : "", "family" : "Read", "given" : "N W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McFarlane", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kinsman", "given" : "R I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bates", "given" : "T E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blackhall", "given" : "N W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Farrar", "given" : "G B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hall", "given" : "J C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moss", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "A P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Neill", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "1984", "2" ] ] }, "note" : "NULL", "page" : "274-80", "title" : "Effect of infusion of nutrient solutions into the ileum on gastrointestinal transit and plasma levels of neurotensin and enteroglucagon.", "type" : "article-journal", "volume" : "86" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(173,174)", "plainTextFormattedCitation" : "(173,174)", "previouslyFormattedCitation" : "(173,174)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(173,174). Ileal brake is mediated by peptide YY via vagal pathwayADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1152/ajpgi.00230.2003", "ISSN" : "0193-1857", "PMID" : "14613922", "abstract" : "Although the enteric reflex pathway triggered by volume distension is known to depend on an adrenergic nerve, it is not known whether the slowing of intestinal transit by fat or peptide YY (PYY) also depends on an adrenergic pathway. The aim of this study was to test the hypotheses that the slowing of transit by fat or PYY may depend on a beta-adrenergic pathway, and this adrenergic pathway may act via the serotonergic and opioid pathways previously observed for the slowing of transit by fat. Eighteen dogs were equipped with duodenal and midgut fistulas. The small intestine was compartmentalized into the proximal and distal half of gut. The role of adrenergic, serotonergic, and opioid pathways was then tested in the slowing of intestinal transit by fat, PYY, and norepinephrine. Intestinal transit results were compared as the cumulative percent marker of recovery over 30 min. We found that the slowing of transit by fat, PYY, or norepinephrine was reversed by propranolol. In addition, the slowing effect of fat was reversed by metoprolol (beta1-adrenoreceptor antagonist) but not phentolamine (alpha-adrenoreceptor antagonist). Furthermore, norepinephrine-induced slowing of transit was reversed by ondansetron (5-HT3 receptor antagonist) or naloxone (opioid receptor antagonist). Extending these physiological results, we also found by immunohistochemistry that beta1-adrenoreceptors are expressed by neurons of the intrinsic plexuses of the small intestine. We conclude that the slowing of intestinal transit by fat or PYY depends on a beta-adrenergic pathway and that this adrenergic pathway acts on serotonergic and opioid pathways.", "author" : [ { "dropping-particle" : "", "family" : "Lin", "given" : "Henry C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Neevel", "given" : "Corynn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Peng-Sheng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suh", "given" : "Gina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Jin Hai", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Physiology - Gastrointestinal and Liver Physiology", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2003", "12" ] ] }, "note" : "NULL", "page" : "G1310-G1316", "title" : "Slowing of intestinal transit by fat or peptide YY depends on \u03b2-adrenergic pathway", "type" : "article-journal", "volume" : "285" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(175)", "plainTextFormattedCitation" : "(175)", "previouslyFormattedCitation" : "(175)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(175). It has been shown that patients with CP particularly those with exocrine insufficiency have abnormal digestive and interdigestive antroduodenal motility, which is corrected by pancreatic enzyme supplementationADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0193-1857", "PMID" : "10712266", "abstract" : "In patients with chronic pancreatitis (CP) the relation among exocrine pancreatic secretion, gastrointestinal hormone release, and motility is disturbed. We studied digestive and interdigestive antroduodenal motility and postprandial gut hormone release in 26 patients with CP. Fifteen of these patients had pancreatic insufficiency (PI) established by urinary para-aminobenzoic acid test and fecal fat excretion. Antroduodenal motility was recorded after ingestion of a mixed liquid meal. The effect of pancreatic enzyme supplementation was studied in 8 of the 15 CP patients with PI. The duration of the postprandial antroduodenal motor pattern was significantly (P < 0.01) prolonged in CP patients (324 +/- 20 min) compared with controls (215 +/- 19 min). Antral motility indexes in the first hour after meal ingestion were significantly reduced in CP patients. The interdigestive migrating motor complex cycle length was significantly (P < 0.01) shorter in CP patients (90 +/- 8 min) compared with controls (129 +/- 8 min). These abnormalities were more pronounced in CP patients with exocrine PI. After supplementation of pancreatic enzymes, these alterations in motility reverted toward normal. Digestive and interdigestive antroduodenal motility are abnormal in patients with CP but significantly different from controls only in those with exocrine PI. These abnormalities in antroduodenal motility in CP are related to maldigestion.", "author" : [ { "dropping-particle" : "", "family" : "Vu", "given" : "M K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vecht", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eddes", "given" : "E H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Biemond", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lamers", "given" : "C B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Masclee", "given" : "A A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American journal of physiology. Gastrointestinal and liver physiology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2000", "3" ] ] }, "note" : "NULL", "page" : "G458-66", "title" : "Antroduodenal motility in chronic pancreatitis: are abnormalities related to exocrine insufficiency?", "type" : "article-journal", "volume" : "278" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(176)", "plainTextFormattedCitation" : "(176)", "previouslyFormattedCitation" : "(176)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(176). Alteration of ileal brake with abnormal intestinal motility may lead to abdominal pain, discomfort, postprandial bloating and fullness. These symptoms may be relieved by enzyme supplementation. (ii) Treat sub-clinical maldigestion and thus help regain weight. (iii) contribute to a better glycemic control in those with diabetes. Antioxidants may also be helpful in pain treatment. Normally, cells are in a state of redox homeostasis that means that the free radicals (FR) or reactive oxygen species (ROS) generated during the respiratory cycle are scavenged by the antioxidants. Oxidative stress (OS) refers to an imbalance between pro-oxidants and antioxidants with increased free radical formationADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/01926230290166724", "ISSN" : "0192-6233", "PMID" : "12512863", "abstract" : "Reactive oxygen species (ROS) and other radicals are involved in a variety of biological phenomena, such as mutation, carcinogenesis, degenerative and other diseases, inflammation, aging, and development. ROS are well recognized for playing a dual role as deleterious and beneficial species. The objectives of this review are to describe oxidative stress phenomena, terminology, definitions, and basic chemical characteristics of the species involved; examine the biological targets susceptible to oxidation and the defense mechanisms of the organism against these reactive metabolites; and analyze methodologies, including immunohistochemical markers, used in toxicological pathology in the visualization of oxidative stress phenomena. Direct detection of ROS and other free radicals is difficult, because these molecules are short-lived and highly reactive in a nonspecific manner. Ongoing oxidative damage is, thus, generally analyzed by measurement of secondary products including derivatives of amino acids, nuclei acids, and lipid peroxidation. Attention has been focused on electrochemical methods based on voltammetry measurements for evaluating the total reducing power of biological fluids and tissues. This approach can function as a tool to assess the antioxidant-reducing profile of a biological site and follow changes in pathological situations. This review thus includes different topics essential for understanding oxidative stress phenomena and provides tools for those intending to conduct study and research in this field.", "author" : [ { "dropping-particle" : "", "family" : "Kohen", "given" : "Ron", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nyska", "given" : "Abraham", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Toxicologic pathology", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2002", "10" ] ] }, "note" : "NULL", "page" : "620-50", "title" : "Oxidation of biological systems: oxidative stress phenomena, antioxidants, redox reactions, and methods for their quantification.", "type" : "article-journal", "volume" : "30" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(177)", "plainTextFormattedCitation" : "(177)", "previouslyFormattedCitation" : "(177)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(177). Either an increased production of ROS or a deficient antioxidant capacity of the cell may lead to OS. Increased FR production may occur due to exogenous sources such as pollutants, xenobiotics, smoking etc. or endogenously through respiratory burst. Mild oxidative stress is countered by cellular responses. If, however, ROS production is increased excessively, the antioxidant capacity may be overwhelmed resulting in OS. Pathological effects of ROS include lipid peroxidation, alteration in redox-sensitive signaling pathways, inflammation, and cell injury. Severe oxidative stress can even cause cell death.OS as a mechanism of inflammation in CP has been shown for the past 30 years. Many studies have shown increased OS and deficient antioxidant capacity in patients with CPADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0885-3177", "PMID" : "11291927", "abstract" : "To determine the possible role of oxidative stress in alcoholic pancreatitis, the authors measured the ability of blood neutrophils of 22 patients with acute and 20 patients with chronic alcoholic pancreatitis to produce superoxide anion (O2-) and hydrogen peroxide (H2O2), spontaneously and after in vitro stimulation with phorbol ester and compared it with that of neutrophils isolated from the blood of 16 healthy controls. In addition, they measured serum activities of superoxide dismutase, catalase, and the serum concentration of glutathione peroxidase (GPx). Phorbol ester-induced O2- and H2O2 production in neutrophils of patients with acute and chronic pancreatitis was greater than in controls, but these differences, except of superoxide anion production by neutrophils of patients with chronic pancreatitis, were not statistically significant because of large individual differences. Spontaneous resting production of O2- and H2O2 by neutrophils of patients with chronic pancreatitis was significantly greater than in the controls. Superoxide dismutase and catalase activity was greater in sera of both groups of patients with acute and chronic alcoholic pancreatitis than in controls, but GPx concentration was significantly less in the sera of patients with chronic pancreatitis. Impaired GPx production and increased production of O2- and H2O2 by neutrophils may result in increased lipid peroxidation and could play a role in the pathogenesis of chronic alcoholic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Szuster-Ciesielska", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Daniluk", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kandefer-Szersze\u0144", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreas", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2001", "4" ] ] }, "note" : "NULL", "page" : "261-6", "title" : "Oxidative stress in blood of patients with alcohol-related pancreatitis.", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1007/BF02788386", "ISSN" : "0169-4197", "PMID" : "9444552", "abstract" : "CONCLUSION Cu/Zn-SOD is present in pancreatic juice and tissue. Immunohistochemical studies reveal a localization of this enzyme in islet, duct, and centroacinar cells, but to a much lower extent in pancreatic acinar cells. BACKGROUND It is generally accepted that oxygen radicals are involved in the pathogenesis of acute and chronic pancreatitis. An imbalance of radical-generating and radical-scavenging processes is thought to lead to the damage of pancreatic acinar cells that initiate the autodigestion of the whole organ. METHODS We investigated the distribution pattern of the cytosolic radical-scavenging enzyme, copper/zinc-superoxide dismutase (Cu/Zn-SOD), in pancreatic juice and tissue. In patients with chronic pancreatitis or pancreatic malignancies, Cu-Zn-SOD was quantitated in different fractions of pancreatic juice by means of an enzyme immunoassay using two Cu/Zn-SOD-specific monoclonal antibodies. Cryostat or paraffin sections of pancreatic tissue were analyzed by immunohistochemical techniques. RESULTS We found this enzyme to be present in the first secretin-triggered fraction of endoscopically obtained pancreatic juice in concentrations similar to serum. In contrast, after cholecystokinin stimulation, only low levels could be found in pancreatic juice, indicating that this enzyme is not actively secreted. Interestingly, pancreatic juice of patients with chronic pancreatitis or pancreas tumor contained higher levels (25-29 ng/mL) of Cu/Zn-SOD than juice of controls without pancreatic diseases (15 ng/mL). Immunohistochemical studies of Cu/Zn-SOD in pancreatic tissue revealed a more intense staining of duct cells, islet cells, and centroacinar cells, whereas acinar cells showed almost no staining for Cu/Zn-SOD.", "author" : [ { "dropping-particle" : "", "family" : "Hausmann", "given" : "D H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Porstmann", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weber", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hausmann", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dummler", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liebe", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Emmrich", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International journal of pancreatology : official journal of the International Association of Pancreatology", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "1997", "12" ] ] }, "note" : "NULL", "page" : "207-13", "title" : "Cu/Zn-SOD in human pancreatic tissue and pancreatic juice.", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISSN" : "0163-2116", "PMID" : "8654156", "abstract" : "Free radicals have been suspected to play a role in the pathogenicity of alcohol-related chronic pancreatitis. The aim of this study was to determine the status of several antioxidant parameters in these patients and examine the factors that are likely to influence them. Thirty-five subjects (23 males and 12 females, mean age 48 +/- 8 years) with disease proven by endoscopic pancreatography and 14 healthy controls (6 males and 8 females, mean age 44 +/- 7 years) were included in the study. Biochemical antioxidant parameters included: selenium, zinc, and copper levels in plasma; glutathione peroxidase in plasma and erythrocytes; plasma malondialdehyde concentrations assessed by thiobarbituric acid reactants; and serum vitamin E and A levels. Selenium and vitamin E oral intake was assessed by a five-day diet analysis. Hemoglobin (130 +/- 16 vs 143 +/- 15 g/liter), vitamin E (8 +/- 5 vs 16 +/- 9 mg/liter), vitamin A (30 +/- 11 vs 49 +/- 12 micrograms/dl), selenium (54 +/- 20 vs 87 +/- 11 micrograms/liter), and plasma glutathione peroxidase (903 +/- 313 vs 1326 +/- 168 units/liter) were significantly lower in patients than in controls (P < 0.05). In contrast, white blood cell count, C-reactive protein, and plasma copper levels were significantly higher in patients than in controls. Cholesterol, triglycerides, iron, ferritin, total proteins, zinc, and malondialdehyde were not different. Vitamin E was lower in patients with steatorrhea, while vitamin A was lower in patients with concomitant diabetes mellitus. Dietary intakes were not different between patients and controls. In conclusion, patients with alcohol-related chronic pancreatitis have low blood levels in many antioxidant factors. Dietary intakes of some of them (selenium and vitamin E) are adequate, however. Such deficiencies are secondary to pancreatic insufficiency and probably to increased requirements related to enhanced oxidative stress.", "author" : [ { "dropping-particle" : "", "family" : "Gossum", "given" : "A", "non-dropping-particle" : "Van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Closset", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Noel", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cremer", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Neve", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Digestive diseases and sciences", "id" : "ITEM-3", "issue" : "6", "issued" : { "date-parts" : [ [ "1996", "6" ] ] }, "note" : "NULL", "page" : "1225-31", "title" : "Deficiency in antioxidant factors in patients with alcohol-related chronic pancreatitis.", "type" : "article-journal", "volume" : "41" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "ISSN" : "0021-9746", "PMID" : "1695229", "abstract" : "To ascertain modifications in the activation products derived from oxygen free radicals in patients with chronic pancreatic and extra-pancreatic diseases, lipid peroxide activity was measured in the sera of 40 control subjects, 28 patients with pancreatic cancer, 49 with chronic pancreatitis, and 53 with extra-pancreatic diseases. In 142 of the subjects, elastase 1, amylase, and pancreatic isoamylase activities were also determined. Increased lipid peroxide activities were found in some patients with both chronic pancreatic and extra-pancreatic diseases. Patients with chronic pancreatitis studied during relapse had higher activities of lipid peroxides than those without active disease. No difference was found between the values in patients with pancreatic cancer with liver metastases and those without. Correlations were found between lipid peroxides and both amylase and pancreatic isoamylase activities; no correlation was detected between lipid peroxides and elastase 1. In benign biliary tract disease a correlation was detected between lipid peroxides and alanine aminotransferase and alkaline phosphatase activities. In all patients, however, a correlation was found between alkaline phosphatase and lipid peroxide activities. It is concluded that activation of oxygen derived free radicals occurs in chronic pancreatic as well as in extra-pancreatic disease; it seems to reflect the degree of inflammation.", "author" : [ { "dropping-particle" : "", "family" : "Basso", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Panozzo", "given" : "M P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fabris", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Favero", "given" : "G", "non-dropping-particle" : "del", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meggiato", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fogar", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meani", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Faggian", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Plebani", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burlina", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of clinical pathology", "id" : "ITEM-4", "issue" : "5", "issued" : { "date-parts" : [ [ "1990", "5" ] ] }, "note" : "NULL", "page" : "403-5", "title" : "Oxygen derived free radicals in patients with chronic pancreatic and other digestive diseases.", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "ISSN" : "0036-5521", "PMID" : "8303214", "abstract" : "Micronutrient antioxidants interact with glutathione in tissues to facilitate the disposal of reactive oxygen species and xenobiotic metabolites derived via cytochromes P450. Published evidence linking cytochrome P450I induction with chronic pancreatitis therefore led us to compare antioxidant status in patients at Manchester in the northwest of England and at Madras in the southeast of India. Serum studies in healthy volunteers showed that the biologic availabilities of selenium and alpha-tocopherol were equally high in the two zones but that the availabilities of beta-carotene and ascorbic acid were lower in the tropical area (p < 0.001), where the ratio of ascorbic acid to total vitamin C concentration in serum was substantially reduced (p < 0.001). The serum antioxidant profiles of the chronic pancreatitis groups reflected these indigenous differences: a decrement in selenium and alpha-tocopherol was evident in both zones, whereas beta-carotene and ascorbic acid values were subnormal only in the Manchester group. The concentration of inorganic sulphate in urine--an index of long-term intake of sulphur amino acids for synthesis of glutathione and other detoxifiers--was similar in controls and patients from Manchester, but levels were lower than in their Madras counterparts (p < 0.02, p < 0.01, respectively). The results suggest that culinary practices that erode the biologic availabilities of ascorbic acid and beta-carotene may predispose to pancreatic oxidative stress and thereby to the changes leading to chronic pancreatitis at an early age in south India. These findings have implications for treatment and prophylaxis.", "author" : [ { "dropping-particle" : "", "family" : "Braganza", "given" : "J M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schofield", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Snehalatha", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of gastroenterology", "id" : "ITEM-5", "issue" : "12", "issued" : { "date-parts" : [ [ "1993", "12" ] ] }, "note" : "NULL", "page" : "1098-104", "title" : "Micronutrient antioxidant status in tropical compared with temperate-zone chronic pancreatitis.", "type" : "article-journal", "volume" : "28" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(178\u2013182)", "plainTextFormattedCitation" : "(178\u2013182)", "previouslyFormattedCitation" : "(178\u2013182)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(178–182). Consequent to the understanding that OS might be related to chronic inflammation in patients with CP who have an inadequate antioxidant status, antioxidant supplementation has been used to ameliorate OS and relieve pain in patients with CP. A study from Manchester, UK was the pioneer study. Uden et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0269-2813", "PMID" : "1600043", "abstract" : "The usefulness of micronutrient antioxidant therapy for recurrent (non-gallstone) pancreatitis has recently been endorsed by a 20-week double-blind double-dummy cross-over trial in 20 patients. Treatment was delivered as two types of tablets, providing daily doses of 600 micrograms organic selenium, 9000 i.u. beta-carotene, 0.54 g vitamin C, 270 i.u. vitamin E and 2 g methionine. We report antioxidant profiles in blood samples collected before entry, at the cross-over stage and upon completion of trial. Baseline serum concentrations of selenium, beta-carotene and vitamin E in the patients were significantly lower than in healthy controls, were unaltered by placebo and normalized by active treatment, but reverted to basal values in the subgroup that received placebo subsequently. The baseline serum concentration of a free radical marker--the 9-cis, 11-trans isomer of linoleic acid--was significantly higher in the patients than in controls, fell inexplicably in the placebo phase and fell further upon active treatment. Discriminant analysis eliminated the overlap in free radical marker and selenium concentrations between control sera on the one hand and baseline or post-placebo samples from the patients on the other: antioxidant treatment normalized the relationship between these biochemical parameters. Subnormal baseline serum levels of S-adenosylmethionine drifted downwards upon active treatment whereas a sharp rise was noted when a relapse of pancreatitis occurred during the placebo phase. The results confirm that adequate exposure to antioxidants in the active treatment phase was associated with amelioration of oxidative stress, and that there was no residual effect 10 weeks after switching over to placebo treatment. Furthermore, the paradoxical behaviour of S-adenosylmethionine may imply that the beneficial effect of micronutrient antioxidants in recurrent pancreatitis is linked with preservation of the methionine trans-sulfuration pathway in pancreatic acinar cells.", "author" : [ { "dropping-particle" : "", "family" : "Uden", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schofield", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miller", "given" : "P F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Day", "given" : "J P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bottiglier", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Braganza", "given" : "J M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Alimentary pharmacology & therapeutics", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "1992", "4" ] ] }, "note" : "NULL", "page" : "229-40", "title" : "Antioxidant therapy for recurrent pancreatitis: biochemical profiles in a placebo-controlled trial.", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(183)", "plainTextFormattedCitation" : "(183)", "previouslyFormattedCitation" : "(183)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(183) used a combination of dietary antioxidants (600 μg organic selenium, 9000 IU β -carotene, 0.54 g vitamin C, 270 IU vitamin E and 2 g methionine) and showed significant pain relief in patients with recurrent acute and chronic pancreatitis. In an observational study, Whiteley et al.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Whiteley G, Kienle A", "given" : "Lee S et al.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreas", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "1994" ] ] }, "page" : "A807", "title" : "Micronutrient antioxidant therapy in the nonsurgical management of painful chronic pancreatitis: long term observation", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(184)", "plainTextFormattedCitation" : "(184)", "previouslyFormattedCitation" : "(184)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(184) studied the effect of micronutrient supplementation in 103 patients with CP and showed that 75 patients remained pain free during a follow-up period of 9 years. There have been a total of 10 RCTs on the role of antioxidants in patients with CP. In a study of 36 patients by Kirk et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.gassur.2005.08.035", "ISSN" : "1091-255X", "PMID" : "16627214", "abstract" : "Patients with chronic pancreatitis (CP) typically suffer intractable abdominal pain that is resistant to most analgesic strategies. Recent research indicates that the pain of CP may be in part due to oxygen free radical induced pancreatic damage. Using a randomized, double-blind, placebo-controlled crossover trial, we evaluated the efficacy of a combined antioxidant preparation in the management of CP. Patients with confirmed chronic pancreatitis (N = 36) were randomized to receive treatment with either Antox, which contains the antioxidants selenium, betacarotene, L-methionine, and vitamins C and E, or placebo for 10 weeks. Each group of patients then switched to receive the alternative treatment for a further 10 weeks. Markers of antioxidant status were measured by blood sampling, whereas quality of life and pain were assessed using the SF-36 questionnaire. Nineteen patients completed the full 20 weeks of treatment. Treatment with Antox was associated with significant improvements in quality of life in terms of pain (+17 antioxidant vs. -7 placebo), physical (+9 vs. -3) and social functioning (+8 vs. -7), and general health perception (+10 vs. -3). We conclude that treatment with antioxidants may improve quality of life and reduce pain in patients suffering from chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Kirk", "given" : "Gareth R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "White", "given" : "Jonathan S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McKie", "given" : "Lloyd", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stevenson", "given" : "Mike", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Young", "given" : "Ian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clements", "given" : "W D Barry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rowlands", "given" : "Brian J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2006", "4" ] ] }, "note" : "NULL", "page" : "499-503", "title" : "Combined antioxidant therapy reduces pain and improves quality of life in chronic pancreatitis.", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(185)", "plainTextFormattedCitation" : "(185)", "previouslyFormattedCitation" : "(185)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(185), significant improvement in the quality of life and pain was observed. A large, randomized, placebo-controlled trial showed that pain was significantly reduced during 6-month therapy and the benefit was evident as early as 3 monthsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1053/j.gastro.2008.09.028", "ISSN" : "00165085", "PMID" : "18952082", "abstract" : "BACKGROUND & AIMS Oxidative stress has been implicated in the pathophysiology of chronic pancreatitis (CP). We evaluated the effects of antioxidant supplementation on pain relief, oxidative stress, and antioxidant status in patients with CP. METHODS In a placebo-controlled double blind trial, consecutive patients with CP were randomized to groups that were given placebo or antioxidants for 6 months. The primary outcome measure was pain relief, and secondary outcome measures were analgesic requirements, hospitalization, and markers of oxidative stress (thiobarbituric acid-reactive substances [TBARS]) and antioxidant status (ferric-reducing ability of plasma [FRAP]). RESULTS Patients (age 30.5+/-10.5 years, 86 male, 35 alcoholic, and 92 with idiopathic CP) were assigned to the placebo (n=56) or antioxidant groups (n=71). After 6 months, the reduction in the number of painful days per month was significantly higher in the antioxidant group compared with the placebo group (7.4+/-6.8 vs 3.2+/-4, respectively; P< .001; 95% CI, 2.07, 6.23). The reduction in the number of analgesic tablets per month was also higher in the antioxidant group (10.5+/-11.8 vs 4.4+/-5.8 respectively; P= .001; 95% CI, 2.65, 9.65). Furthermore, 32% and 13% of patients became pain free in the antioxidant and placebo groups, respectively (P= .009). The reduction in the level of TBARS and increase in FRAP were significantly higher in the antioxidant group compared with the placebo group (TBARS: placebo 1.2+/-2.7 vs antioxidant 3.5+/-3.4 nmol/mL; P= .001; 95% CI 0.96, 3.55; FRAP: placebo -5.6+/-154.9 vs antioxidant 97.8+/-134.9 microMFe(+2) liberated, P= .001, 95% CI 44.98, 161.7). CONCLUSIONS Antioxidant supplementation was effective in relieving pain and reducing levels of oxidative stress in patients with CP.", "author" : [ { "dropping-particle" : "", "family" : "Bhardwaj", "given" : "Payal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Garg", "given" : "Pramod Kumar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maulik", "given" : "Subir Kumar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saraya", "given" : "Anoop", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tandon", "given" : "Rakesh Kumar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Acharya", "given" : "Subrat Kumar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2009", "1" ] ] }, "note" : "NULL", "page" : "149-159.e2", "title" : "A Randomized Controlled Trial of Antioxidant Supplementation for Pain Relief in Patients With Chronic Pancreatitis", "type" : "article-journal", "volume" : "136" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(186)", "plainTextFormattedCitation" : "(186)", "previouslyFormattedCitation" : "(186)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(186). A recent RCT had shown that antioxidants were ineffective in patients with predominantly alcohol induced CPADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1053/j.gastro.2012.05.046", "ISSN" : "00165085", "PMID" : "22683257", "abstract" : "BACKGROUND & AIMS We investigated whether antioxidant therapy reduces pain and improves quality of life in patients with chronic pancreatitis. METHODS We performed a double-blind, randomized, controlled trial that compared the effects of antioxidant therapy with placebo in 70 patients with chronic pancreatitis. Patients provided 1 month of baseline data and were followed for 6 months while receiving either antioxidant therapy (Antox version 1.2, Pharma Nord, Morpeth, UK) or matched placebo (2 tablets, 3 times/day). The primary analysis was baseline-adjusted change in pain score at 6 months, assessed by an 11-point numeric rating scale. Secondary analyses included alternative assessments of clinical and diary pain scores, scores on quality-of-life tests (the European Organization for Research and Treatment of Cancer [EORTC-QLQ-C30], Quality of Life Questionnaire-Pancreatic modification [QLQ-PAN28], European Quality of Life questionnaire [EuroQOL EQ-5D], and European Quality of Life questionnaire - Visual Analog Score [EQ-VAS]), levels of antioxidants, use of opiates, and adverse events. Analyses, reported by intention to treat, were prospectively defined by protocol. RESULTS After 6 months, pain scores reported to the clinic were reduced by 1.97 from baseline in the placebo group and by 2.33 in the antioxidant group but were similar between groups (-0.36; 95% confidence interval [CI], -1.44 to 0.72; P = .509). Average daily pain scores from diaries were also similar (3.05 for the placebo group and 2.93 for the antioxidant group, a difference of 0.11; 95% CI, 1.05-0.82; P = .808). Measures of quality of life were similar between groups, as was opiate use and number of hospital admissions and outpatient visits. Blood levels of vitamin C and E, \u03b2-carotene, and selenium were increased significantly in the antioxidant group. CONCLUSIONS Administration of antioxidants to patients with painful chronic pancreatitis of predominantly alcoholic origin does not reduce pain or improve quality of life, despite causing a sustained increase in blood levels of antioxidants.", "author" : [ { "dropping-particle" : "", "family" : "Siriwardena", "given" : "Ajith K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mason", "given" : "James M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sheen", "given" : "Aali J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Makin", "given" : "Alistair J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "Nehal S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2012", "9" ] ] }, "note" : "NULL", "page" : "655-663.e1", "title" : "Antioxidant Therapy Does Not Reduce Pain in Patients With Chronic Pancreatitis: The ANTICIPATE Study", "type" : "article-journal", "volume" : "143" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(187)", "plainTextFormattedCitation" : "(187)", "previouslyFormattedCitation" : "(187)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(187). However, several shortcomings of the study such as improper patient selection, continued alcohol intake and smoking, opiate dependence, failed endoscopic/surgical therapy etc. limited the generalizability of the studyADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1053/j.gastro.2012.12.031", "ISSN" : "1528-0012", "PMID" : "23352593", "author" : [ { "dropping-particle" : "", "family" : "Garg", "given" : "Pramod Kumar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2013", "3" ] ] }, "note" : "NULL", "page" : "e19-20", "title" : "Antioxidants for chronic pancreatitis: reasons for disappointing results despite sound principles.", "type" : "article-journal", "volume" : "144" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1053/j.gastro.2012.12.034", "ISSN" : "1528-0012", "PMID" : "23357060", "author" : [ { "dropping-particle" : "", "family" : "Braganza", "given" : "Joan M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2013", "3" ] ] }, "page" : "e17-8", "title" : "Limitations of patient selection and other issues in chronic pancreatitis antioxidant trial.", "type" : "article-journal", "volume" : "144" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(188,189)", "plainTextFormattedCitation" : "(188,189)", "previouslyFormattedCitation" : "(188,189)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(188,189). Recent meta-analyses have shown beneficial effect of antioxidants in patients with CPADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/14651858.CD008945.pub2", "ISSN" : "1469-493X", "PMID" : "25144441", "abstract" : "BACKGROUND Reduced intake and absorption of antioxidants due to pain and malabsorption are probable causes of the lower levels of antioxidants observed in patients with chronic pancreatitis (CP). Improving the status of antioxidants might be effective in slowing the disease process and reducing pain in CP. OBJECTIVES To assess the benefits and harms of antioxidants for the treatment of pain in patients with CP. SEARCH METHODS We searched\u00a0the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Conference Proceedings Citation Index from inception to October 2012. Two review authors performed the selection of trials independently. SELECTION CRITERIA We included all randomised controlled trials (RCTs) evaluating antioxidants for treatment of pain in CP. All trials were included irrespective of blinding, numbers of participants randomly assigned and language of the article. DATA COLLECTION AND ANALYSIS Two review authors extracted data independently. The risk of bias of included trials was assessed. Study authors were asked for additional information in the case of missing data. MAIN RESULTS Twelve RCTs with a total of 585 participants were included. Six trials were double-blinded, placebo-controlled studies, and the other six trials were of less adequate methodology. Most trials were small and had high rates of dropout. Eleven of the 12 included trials described the effects of antioxidants on chronic abdominal pain in chronic pancreatitis. Pain as measured on a visual analogue scale (VAS, scale range 0 to 10) after one to six months was less in the antioxidant group than in the control group (mean difference (MD) -0.33, 95% confidence interval (CI) -0.64 to -0.02, P value 0.04, moderate-quality evidence). The number of pain-free participants was not statistically significantly different (risk ratio (RR) 1.73, 95% CI 0.95 to 3.15, P value 0.07, low-quality evidence). More adverse events were observed in the antioxidant group, both in the parallel trials (RR 4.43, 95% CI 1.60 to 12.29, P value 0.0004, moderate-quality evidence) and in the cross-over trials (RR 5.80, 95% CI 1.56 to 21.53, P value 0.0009, moderate-quality evidence). Adverse events occurred in 16% of participants and were mostly mild (e.g. headache, gastrointestinal complaints), but were sufficient to make participants stop antioxidant use. Other important outcomes such as use of analgesics, exacerbation of pancreatitis and quality of life were rarely reported. One \u2026", "author" : [ { "dropping-particle" : "", "family" : "Ahmed Ali", "given" : "Usama", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jens", "given" : "Sjoerd", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Busch", "given" : "Olivier RC", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keus", "given" : "Frederik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goor", "given" : "Harry", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gooszen", "given" : "Hein G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boermeester", "given" : "Marja A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cochrane Database of Systematic Reviews", "editor" : [ { "dropping-particle" : "", "family" : "Ahmed Ali", "given" : "Usama", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2014", "8", "21" ] ] }, "note" : "NULL", "page" : "CD008945", "publisher" : "John Wiley & Sons, Ltd", "publisher-place" : "Chichester, UK", "title" : "Antioxidants for pain in chronic pancreatitis", "type" : "chapter" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.clnu.2014.07.003", "ISSN" : "1532-1983", "PMID" : "25035087", "abstract" : "BACKGROUND & AIMS Chronic pancreatitis is a progressive, inflammatory disease of pancreas characterized by significant abdominal pain, malabsorption, and diabetes mellitus. Antioxidant therapy has been proposed as an effective treatment for painful chronic pancreatitis. We performed a meta-analysis of trials in which antioxidant therapy was compared with placebo in chronic pancreatitis. METHODS We searched six databases to identify relevant trials. Results are expressed as risk ratio (RR) or standardized mean difference (SMD) with accompanying 95% confidence intervals (CI). The meta-analysis was performed with the fixed-effects model or random-effects model according to heterogeneity. RESULTS Eight studies including 573 patients met the inclusion criteria. A meta-analysis of these studies revealed that the intervention of antioxidants was associated with a significant increase in patients with pain relief (RR, 2.15; 95% CI, 1.72-2.69; P < 0.00001), and a significant decrease in patients' need for analgesics (RR, 0.56; 95% CI, 0.40-0.78; P = 0.0006). For pain score, antioxidants improved pain tolerance in chronic pancreatitis patients (SMD: -0.41; 95% CI: -0.83 to -0.10; P = 0.0005). Additionally, antioxidants may cause some adverse reactions (RR, 4.22; 95% CI: 2.17-8.20; P < 0.0001). CONCLUSIONS Based on current evidence, oxidative stress may play an important role in the pathophysiology of chronic pancreatitis, and administration of antioxidants to patients with painful chronic pancreatitis is effective in relieving pain. Antioxidant supplements may be advocated as one medical therapy for chronic pancreatitis patients with low antioxidant capacity in their blood.", "author" : [ { "dropping-particle" : "", "family" : "Zhou", "given" : "Dongkai", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Weilin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cheng", "given" : "Xiaofei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wei", "given" : "Jianfeng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zheng", "given" : "Shusen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical nutrition (Edinburgh, Scotland)", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2015", "8" ] ] }, "note" : "NULL", "page" : "627-34", "title" : "Antioxidant therapy for patients with chronic pancreatitis: A systematic review and meta-analysis.", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(30,190)", "plainTextFormattedCitation" : "(30,190)", "previouslyFormattedCitation" : "(30,190)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(30,190). Another systematic review and meta-analysis showed that antioxidants may help ameliorate pain in patients with CPADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.pan.2015.01.003", "ISSN" : "1424-3911", "PMID" : "25648074", "abstract" : "BACKGROUND Pain in CP results from inflammation and neuroimmune alterations that are associated with oxidative stress, among other mechanisms. This is marked by depletion of antioxidant defenses including methionine, which is a donor of methyl moieties that maintains the acinar transsulfuration pathway. We performed a systematic review and meta-analysis of trials evaluating methionine-containing antioxidants in CP. PATIENT AND METHODS Literature search was conducted in Medline/Pubmed, EMBASE, and Cochrane databases. Systematic review and meta-analysis was performed per PRISMA guidelines. Main study outcome was pain relief. GRADE system was used for quality assessment. Heterogeneity was assessed by the Q and I(2) measures; publication bias by Egger's test. Random-effect model (DerSimonian and Laird) was used if there was heterogeneity. RESULTS Eight studies (n\u00a0=\u00a0411) were identified that used methionine-containing antioxidants. The study duration ranged from 10 wks to 12 months. All studies used methionine, organic selenium, ascorbate, beta-carotene and alpha-tocoferol. Four studies (including two RCTs) that reported change in pain scores were metaanalyzed. Though overall effect [standardized difference in means (95% CI)] on pain score reduction was\u00a0-0.95 (-1.738 to\u00a0-0.160) (z\u00a0=\u00a0-2.36; p\u00a0=\u00a00.018), the significance was lost when the two RCTs were meta-analyzed. RCTs that reported the number of pain free patients had a statistically significant overall effect of\u00a0-3.204 (p\u00a0=\u00a00.001). Though more patients on methionine containing antioxidants had adverse events, majority of them were mild. CONCLUSION Methionine containing antioxidants appear to result in pain reduction in a significant proportion of CP patients. Further randomized controlled trials with homogeneous outcome measures are needed.", "author" : [ { "dropping-particle" : "", "family" : "Talukdar", "given" : "Rupjyoti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Murthy", "given" : "H V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reddy", "given" : "D Nageshwar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2015", "3" ] ] }, "note" : "NULL", "page" : "136-44", "title" : "Role of methionine containing antioxidant combination in the management of pain in chronic pancreatitis: a systematic review and meta-analysis.", "type" : "article-journal", "volume" : "15" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(191)", "plainTextFormattedCitation" : "(191)", "previouslyFormattedCitation" : "(191)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(191). This analysis included 9 RCTs with 390 patients were included. A combination of antioxidants (selenium, β-carotene, vitamin C, vitamin E, and methionine) showed significant pain relief while studies with single antioxidant therapy showed no significant pain relief. The latest RCT has shown that a combination of pregabalin and antioxidants for 2 months followed by only antioxidants for 4 months resulted in significant pain relief in patients with CP who had recurrence of pain after ductal clearance by endotherapy or surgeryADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/jgh.13332", "ISSN" : "1440-1746", "PMID" : "26945817", "abstract" : "BACKGROUND AND AIM The aim of this study was to evaluate the effect of antioxidant-pregabalin combination on pain recurrence in patients with chronic calcific pancreatitis. METHODS In this randomized, double-blind, placebo-controlled trial, chronic calcific pancreatitis patients with pain recurrence following pancreatic ductal clearance of stones received either antioxidant-pregabalin combination or matching placebo for 2\u2009months followed by open-label antioxidants for the next 4\u2009months in both groups. Compliance, daily pain, and adverse events were recorded weekly and at the end of study by a coordinator blinded to treatment status. Primary outcome was pain improvement (visual analog scale and Izbicki score); secondary outcomes were as follows: complete pain resolution, painful days, and adverse events. Number needed-to-treat was calculated. RESULTS We randomized 42 and 45 patients (mean age 29.3\u2009years) to treatment and placebo arms, respectively. Baseline characteristics, including pain scores, were similar for both groups. No patients received high-potency narcotic. At 2\u2009months, a significant improvement in the treatment arm was observed in percent reduction of visual analog scale (-50 [-80.0; -32.1] vs -29.5 [-64.5; 0]; P\u2009=\u20090.01), Izbicki score (14.5 [0; 21.3] vs 30.0 [11.8; 41.3]; P\u2009=\u20090.001), complete pain resolution (20 [47.6%] vs 12 [26.7%]; P\u2009=\u20090.04), and number of painful days (10.0 [2.0; 16.0] vs 18.0 [7.0; 34.0]; P\u2009=\u20090.01). Needed-to-treat was 4.8. Pain reduction persisted at 6\u2009months in the original treatment group (20.0 [15.0; 28.0] vs 36.0 [20.0; 50.0]; P\u2009=\u20090.006). A total of 33 patients in the treatment arm experienced mild to moderate self-limiting nausea/vomiting and drowsiness, respectively and did not require any change in study protocol. CONCLUSION Antioxidant-pregabalin combination results in significant relief in pain recurrence after ductal clearance in narcotic na\u00efve patients with chronic calcific pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Talukdar", "given" : "Rupjyoti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lakhtakia", "given" : "Sundeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nageshwar Reddy", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rao", "given" : "G Venkat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pradeep", "given" : "Rebala", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banerjee", "given" : "Rupa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gupta", "given" : "Rajesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramchandani", "given" : "Mohan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tandan", "given" : "Manu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Murthy", "given" : "H Vivekananda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of gastroenterology and hepatology", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2016", "9" ] ] }, "page" : "1654-62", "title" : "Ameliorating effect of antioxidants and pregabalin combination in pain recurrence after ductal clearance in chronic pancreatitis: Results of a randomized, double blind, placebo-controlled trial.", "type" : "article-journal", "volume" : "31" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(192)", "plainTextFormattedCitation" : "(192)", "previouslyFormattedCitation" : "(192)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(192). Finally, a recent observational study has shown that long-term pain relief may be obtained with optimized medical therapy including antioxidants in patients with CPADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/jgh.13410", "ISSN" : "1440-1746", "PMID" : "27061119", "abstract" : "BACKGROUND AND AIM Abdominal pain is difficult to treat in patients with chronic pancreatitis (CP). Medical therapy including antioxidants has been shown to relieve pain of CP in the short-term. Our aim was to study the long-term results of optimized medical and interventional therapy for pain relief in patients with CP with a step-up approach. METHODS All consecutive patients with CP were included prospectively in the study. They were treated medically with a well-balanced diet, pancreatic enzymes, and antioxidants (9000\u2009IU beta-carotene, 0.54\u2009g vitamin C, 270\u2009IU vitamin E, 600\u2009\u00b5g organic selenium, and 2\u2009g methionine). Endoscopic therapy and/or surgery were offered if medical therapy failed. Pain relief was the primary outcome measure. RESULTS A total of 313 patients (mean age 26.16\u2009\u00b1\u200912.17; 244 males) with CP were included; 288 (92%) patients had abdominal pain. The etiology of CP was idiopathic in 224 (71.6%) and alcohol in 82 (26.2%). At 1-year follow-up, significant pain relief was achieved in 84.7% of patients: 52.1% with medical therapy, 16.7% with endoscopic therapy, 7.6% with surgery, and 8.3% spontaneously. The mean pain score decreased from 6.36\u2009\u00b1\u20091.92 to 1.62\u2009\u00b1\u20092.10 (P\u2009<\u20090.001). Of the 288 patients, 261, 218, 112, and 51 patients were followed up for 3, 5, 10, and 15\u2009years, respectively; 54.0%, 57.3%, 60.7%, and 68.8% of them became pain free at those follow-up periods. CONCLUSION Significant pain relief is achieved in the majority of patients with optimized medical and interventional treatment.", "author" : [ { "dropping-particle" : "", "family" : "Shalimar", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Midha", "given" : "Shallu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hasan", "given" : "Ajmal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dhingra", "given" : "Rajan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Garg", "given" : "Pramod Kumar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of gastroenterology and hepatology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2017", "1" ] ] }, "page" : "270-277", "title" : "Long-term pain relief with optimized medical treatment including antioxidants and step-up interventional therapy in patients with chronic pancreatitis.", "type" : "article-journal", "volume" : "32" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(193)", "plainTextFormattedCitation" : "(193)", "previouslyFormattedCitation" : "(193)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(193). Overall, except for one RCTADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1053/j.gastro.2012.05.046", "ISSN" : "00165085", "PMID" : "22683257", "abstract" : "BACKGROUND & AIMS We investigated whether antioxidant therapy reduces pain and improves quality of life in patients with chronic pancreatitis. METHODS We performed a double-blind, randomized, controlled trial that compared the effects of antioxidant therapy with placebo in 70 patients with chronic pancreatitis. Patients provided 1 month of baseline data and were followed for 6 months while receiving either antioxidant therapy (Antox version 1.2, Pharma Nord, Morpeth, UK) or matched placebo (2 tablets, 3 times/day). The primary analysis was baseline-adjusted change in pain score at 6 months, assessed by an 11-point numeric rating scale. Secondary analyses included alternative assessments of clinical and diary pain scores, scores on quality-of-life tests (the European Organization for Research and Treatment of Cancer [EORTC-QLQ-C30], Quality of Life Questionnaire-Pancreatic modification [QLQ-PAN28], European Quality of Life questionnaire [EuroQOL EQ-5D], and European Quality of Life questionnaire - Visual Analog Score [EQ-VAS]), levels of antioxidants, use of opiates, and adverse events. Analyses, reported by intention to treat, were prospectively defined by protocol. RESULTS After 6 months, pain scores reported to the clinic were reduced by 1.97 from baseline in the placebo group and by 2.33 in the antioxidant group but were similar between groups (-0.36; 95% confidence interval [CI], -1.44 to 0.72; P = .509). Average daily pain scores from diaries were also similar (3.05 for the placebo group and 2.93 for the antioxidant group, a difference of 0.11; 95% CI, 1.05-0.82; P = .808). Measures of quality of life were similar between groups, as was opiate use and number of hospital admissions and outpatient visits. Blood levels of vitamin C and E, \u03b2-carotene, and selenium were increased significantly in the antioxidant group. CONCLUSIONS Administration of antioxidants to patients with painful chronic pancreatitis of predominantly alcoholic origin does not reduce pain or improve quality of life, despite causing a sustained increase in blood levels of antioxidants.", "author" : [ { "dropping-particle" : "", "family" : "Siriwardena", "given" : "Ajith K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mason", "given" : "James M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sheen", "given" : "Aali J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Makin", "given" : "Alistair J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "Nehal S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2012", "9" ] ] }, "note" : "NULL", "page" : "655-663.e1", "title" : "Antioxidant Therapy Does Not Reduce Pain in Patients With Chronic Pancreatitis: The ANTICIPATE Study", "type" : "article-journal", "volume" : "143" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(187)", "plainTextFormattedCitation" : "(187)", "previouslyFormattedCitation" : "(187)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(187), all studies have shown significant pain relief with a combination of antioxidants in patients with CP. Asbj?rn Mohr Drewes, S?ren Schou Olesen & Eva SzigethyQ6. Which analgesics are recommended for pain in chronic pancreatitis?Currently the standard guideline for analgesic therapy in CP follows the principles of the “pain relief ladder” provided by the World Health Organization (WHO) adjusted to the pain characteristics of this condition (Quality assessment: moderate; Recommendation: strong; Agreement: strong) The individual experience and manifestation of pain is influenced by a complex series of interactions involving sensory, pathophysiological, affective, socio-cultural, behavioural and cognitive elementsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s11916-012-0274-y", "ISSN" : "1534-3081", "PMID" : "22585314", "abstract" : "Regular assessment for the presence of pain and response to pain management strategies should be high priority in cancer patients. Pain is a multidimensional experience in cancer patients. Pain management will be most effective when treatments are individualized after exploring the various physical and non-physical components of pain, and the patient and family are educated and involved in decision making. This article discusses the various issues that are pertinent to the assessment of pain in cancer patients.", "author" : [ { "dropping-particle" : "", "family" : "Dalal", "given" : "Shalini", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruera", "given" : "Eduardo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current pain and headache reports", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2012", "8", "15" ] ] }, "note" : "NULL", "page" : "314-24", "title" : "Assessing cancer pain.", "type" : "article-journal", "volume" : "16" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(194)", "plainTextFormattedCitation" : "(194)", "previouslyFormattedCitation" : "(194)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(194). Hence, there is always more to analgesia than analgesics, but pharmacological treatment is still the mainstay of pain treatment in CPADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0032-5473", "PMID" : "6514647", "author" : [ { "dropping-particle" : "", "family" : "Twycross", "given" : "R G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Postgraduate medical journal", "id" : "ITEM-1", "issue" : "710", "issued" : { "date-parts" : [ [ "1984", "12" ] ] }, "note" : "NULL", "page" : "876-80", "title" : "Analgesics.", "type" : "article-journal", "volume" : "60" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(195)", "plainTextFormattedCitation" : "(195)", "previouslyFormattedCitation" : "(195)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(195). Of note, the absorption of drugs can potentially be difficult to predict due to e.g., changes in the intestinal pH, ischemia and bacterial overgrowth in patients with CP. Until now only one study has studied these patients. Despite a normal absorption of pregabalin was found there is an unmet need for further studies in more complicated moleculesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1742-7843.2012.00914.x", "ISSN" : "1742-7843", "PMID" : "22716224", "abstract" : "It was recently shown that pregabalin decreased pain associated with chronic pancreatitis. It is well known that pancreatitis patients suffer from fat malabsorption with accompanying diarrhoea because of loss of exocrine pancreatic enzyme production. This may lead to changes in the mucosal surface in the small intestine and possibly affect the absorption of pregabalin. The pharmacokinetics of pregabalin has never been investigated in patients suffering from chronic pancreatitis. The aim of this study was to develop a population pharmacokinetic model of pregabalin administered to patients with chronic pancreatitis. The pregabalin population pharmacokinetic analysis was conducted on data from fifteen patients with chronic pancreatitis. Each patient received 75 mg of pregabalin (oral capsule). Pregabalin concentrations were measured using a validated liquid chromatographic method. Data analysis was performed using non-linear mixed effects modelling methodology as implemented by NONMEM. A one-compartment model with first-order absorption and elimination adequately described pregabalin pharmacokinetics. Time to maximum observed plasma concentration (T(max) ) was 1.53 (95% CI 1.09-2.05). The maximum plasma concentration (C(max) ) was 1.98 \u03bcg/ml (95% CI 1.69-2.34), and area under the plasma concentration-time profile (area under the curve) was 18.2 \u03bcg*hr/ml (95% CI 14.7-26.3). Pregabalin is well absorbed in patients with chronic pancreatitis, and the pharmacokinetic profile of pregabalin is not extensively affected by chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Olesen", "given" : "Anne E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olofsen", "given" : "Erik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olesen", "given" : "S\u00f8ren S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Staahl", "given" : "Camilla", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andresen", "given" : "Trine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dahan", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Basic & clinical pharmacology & toxicology", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2012", "12" ] ] }, "note" : "NULL", "page" : "385-90", "title" : "The absorption profile of pregabalin in chronic pancreatitis.", "type" : "article-journal", "volume" : "111" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(196)", "plainTextFormattedCitation" : "(196)", "previouslyFormattedCitation" : "(196)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(196). Pharmacokinetics can also be changed in patients having problems with intake of tablets, and patch formulations with slow absorption of analgesics may be considered. 1257300145415000Currently the standard guidelines for analgesic therapy in CP follow the principles of the “pain relief ladder” provided by the World Health Organization (WHO). This principle, which was originally launched for cancer pain treatment, is based on the serial introduction of drugs with increasing analgesic potency. This approach enables a simple stepwise escalation of drugs with increasing analgesic potency (level I-III) until pain relief is obtained, with simultaneous monitoring and handling of side effects (figure 1)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0098-7484", "PMID" : "7500538", "abstract" : "OBJECTIVE To perform a systematic review of studies evaluating the effectiveness of the World Health Organization (WHO) analgesic ladder as an intervention for cancer pain management. DATA SOURCES Systematic search of MEDLINE from 1982 to 1995, hand search of textbooks and meeting proceedings, reference lists, and direct contact with authors. STUDY SELECTION Studies of any methodological design were included if they evaluated patients with cancer pain treated according to the WHO analgesic ladder and if the studies provided enough information to estimate the proportion of patients who achieved adequate analgesia with the use of the ladder. The strength of the evidence provided by each study was assessed separately by both authors using current concepts. DATA EXTRACTION From the hard copy of each study report, the first author's name, publication year, study design, number of dropouts per study, and proportion of patients with adequate analgesia in each study were extracted. DATA SYNTHESIS Eight studies purporting to evaluate the effectiveness of the WHO ladder were included in the review. Meta-analysis was not performed because the studies were case series with no control groups. The studies had other limitation: none provided information on the conditions in which pain was assessed; two were retrospective; one had short follow-up periods; three had high withdrawal rates; and one had variable follow-up periods. Analgesia was adequate in 69% to 100% of patients analyzed in the studies. CONCLUSIONS The studies available provide valuable information on the course of cancer pain and its treatment. However, the evidence they provide is insufficient to estimate confidently the effectiveness of the WHO analgesic ladder for the management of cancer pain. Until results from carefully designed controlled trials are available, it would be inappropriate to judge the performance of clinicians, programs, and institutions or to design policies based on such evidence.", "author" : [ { "dropping-particle" : "", "family" : "Jadad", "given" : "A R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Browman", "given" : "G P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "JAMA", "id" : "ITEM-1", "issue" : "23", "issued" : { "date-parts" : [ [ "1995", "12", "20" ] ] }, "note" : "NULL", "page" : "1870-3", "title" : "The WHO analgesic ladder for cancer pain management. Stepping up the quality of its evaluation.", "type" : "article-journal", "volume" : "274" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(197)", "plainTextFormattedCitation" : "(197)", "previouslyFormattedCitation" : "(197)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(197). In the following the analgesics most used are described, and where possible special studies and precautions for CP are highlighted: 114300-1905Figure 1: Modified version of the WHO analgesic pain ladder. At level 1 treatment with non-opioids such as paracetamol and non-steroidal anti-inflammatory drugs will be initiated with or without adjuvants. If pain increases or persists level 2 treatment will be initiated. Level 2 treatment include opioids for mild or moderate pain with or without adjuvants. If pain still persists or increases, level 3 treatment may be initiated. Level 3 treatment includes opioids for moderate or severe pain with or without non-opioids and/or adjuvants. Laxatives shall always be considered when opioids are used.00Figure 1: Modified version of the WHO analgesic pain ladder. At level 1 treatment with non-opioids such as paracetamol and non-steroidal anti-inflammatory drugs will be initiated with or without adjuvants. If pain increases or persists level 2 treatment will be initiated. Level 2 treatment include opioids for mild or moderate pain with or without adjuvants. If pain still persists or increases, level 3 treatment may be initiated. Level 3 treatment includes opioids for moderate or severe pain with or without non-opioids and/or adjuvants. Laxatives shall always be considered when opioids are used.Simple analgesics are used as a cornerstone in pain treatment and paracetamol is the preferred level I drug due to its limited side effects. It must be used with caution in patients with concomitant liver impairment or severe malnutrition, but otherwise there are no major restrictions. The non-steroidal anti-inflammatory drugs (NSAIDs) should in general be avoided due to their gastrointestinal toxicity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "1532-1916; 1521-6918", "abstract" : "Despite modern advances in cancer research, screening and treatment options, gastrointestinal tumours remain a leading cause of death worldwide. Both oesophageal and colorectal malignancies carry high rates of morbidity and mortality, presenting a challenge to clinicians in search of effective management strategies. In recent years, the increasing burden of disease has led to a paradigm shift in our approach from treatment to prevention. Among several agents postulated as having a chemopreventive effect on the gastrointestinal tract, aspirin has been most widely studied and has gained universal acknowledgement. There is an expanding evidence base for aspirin as a key mediator in the prevention of dysplastic change in Barrett's oesophagus and colorectal adenomas. Its cardioprotective effects also impact positively on the patient population in question, many of whom have ischaemic vascular disease. The major side effects of aspirin have been well-characterised and may cause significant morbidity and mortality in their own right. Complications such as peptic ulceration, upper gastrointestinal bleeding and haemorrhagic stroke pose serious threats to the routine administration of aspirin and hence a balance between the risks and benefits must be struck if chemoprevention is to be effective on a large scale. In this review, we address the current evidence base for aspirin use in gastrointestinal oncology, as well as several key questions surrounding its safety, cost effectiveness and optimal dose.", "author" : [ { "dropping-particle" : "", "family" : "Thiagarajan", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jankowski", "given" : "J A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Best practice {&} research.Clinical gastroenterology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2012", "4" ] ] }, "note" : "CI: Copyright (c) 2012; GR: Cancer Research UK/United Kingdom; GR: Wellcome Trust/United Kingdom; JID: 101120605; 0 (Anti-Inflammatory Agents, Non-Steroidal); 50-78-2 (Aspirin); 2012/01/17 [received]; 2012/01/17 [accepted]; ppublish", "page" : "197-206", "title" : "Aspirin and NSAIDs; benefits and harms for the gut", "type" : "article-journal", "volume" : "26" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(198)", "plainTextFormattedCitation" : "(198)", "previouslyFormattedCitation" : "(198)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(198). This may especially be relevant in CP as patients are already predisposed to peptic ulcer and have decreased duodenal pH due to insufficient buffering with bicarbonateADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3748/wjg.v19.i42.7282", "ISSN" : "2219-2840", "PMID" : "24259959", "abstract" : "Despite multiple theories on the pathogenesis of pain in chronic pancreatitis, no uniform and consistently successful treatment strategy exists and abdominal pain still remains the dominating symptom for most patients and a major challenge for clinicians. Traditional theories focussed on a mechanical cause of pain related to anatomical changes and evidence of increased ductal and interstitial pressures. These observations form the basis for surgical and endoscopic drainage procedures, but the outcome is variable and often unsatisfactory. This underscores the fact that other factors must contribute to pathogenesis of pain, and has shifted the focus towards a more complex neurobiological understanding of pain generation. Amongst other explanations for pain, experimental and human studies have provided evidence that pain perception at the peripheral level and central pain processing of the nociceptive information is altered in patients with chronic pancreatitis, and resembles that seen in neuropathic and chronic pain disorders. However, pain due to e.g., complications to the disease and adverse effects to treatment must not be overlooked as an additional source of pain. This review outlines the current theories on pain generation in chronic pancreatitis which is crucial in order to understand the complexity and limitations of current therapeutic approaches. Furthermore, it may also serve as an inspiration for further research and development of methods that can evaluate the relative contribution and interplay of different pain mechanisms in the individual patients, before they are subjected to more or less empirical treatment.", "author" : [ { "dropping-particle" : "", "family" : "Poulsen", "given" : "Jakob Lykke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olesen", "given" : "S\u00f8ren Schou", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Malver", "given" : "Lasse Paludan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fr\u00f8kj\u00e6r", "given" : "Jens Br\u00f8ndum", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn Mohr", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "World journal of gastroenterology", "id" : "ITEM-1", "issue" : "42", "issued" : { "date-parts" : [ [ "2013", "11", "14" ] ] }, "note" : "NULL", "page" : "7282-91", "title" : "Pain and chronic pancreatitis: a complex interplay of multiple mechanisms.", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(199)", "plainTextFormattedCitation" : "(199)", "previouslyFormattedCitation" : "(199)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(199). Nonetheless, NSAIDs are very effective in selected patients and may be used for short-term treatments (weeks). The variability in gastrointestinal and cardiac toxicity should be taken into consideration and proton pump inhibitors are normally co-prescribed. In clinical practice level 1 analgesic`s are often insufficient to alleviate pain as monotherapy, but it is important to maintain their use when more potent analgesics are considered.Adjuvant analgesics are a heterogeneous group of drugs initially developed for indications other than pain and include antidepressants, anticonvulsants including the gabapentoids as well as anxiolytics. Although adjuvant analgesics have been widely used in the clinic to treat pain in CP, only the gabapentoid, pregabalin, has been investigated in a placebo controlled randomized trial titrated to 300-600 mg BID. In the short-term, it was found to induce a moderate pain relief with relatively limited side effects when used as an adjuvant analgesic in combination with the patients usual analgesic medication ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1053/j.gastro.2011.04.003", "ISSN" : "1528-0012", "PMID" : "21683078", "author" : [ { "dropping-particle" : "", "family" : "Olesen", "given" : "S\u00f8ren Schou", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bouwense", "given" : "Stefan A W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "Oliver H G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goor", "given" : "Harry", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn Mohr", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2011", "8" ] ] }, "page" : "536-43", "publisher" : "Elsevier Inc.", "title" : "Pregabalin reduces pain in patients with chronic pancreatitis in a randomized, controlled trial.", "type" : "article-journal", "volume" : "141" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(200)", "plainTextFormattedCitation" : "(200)", "previouslyFormattedCitation" : "(200)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(200). Further, a reduction in opioid dose in the short-term may be seen although longer-term studies are neededADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/14651858.CD011522.pub2", "ISSN" : "1469-493X", "PMID" : "26836292", "abstract" : "BACKGROUND Chronic abdominal pain is one of the major symptoms in people with chronic pancreatitis. The role of pregabalin in people with chronic pancreatic pain due to chronic pancreatitis is uncertain. OBJECTIVES To assess the benefits and harms of pregabalin in people with chronic abdominal pain due to chronic pancreatitis. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library 2015, issue 6, and MEDLINE, EMBASE, Science Citation Index Expanded, trials registers until June 2015. We also searched the references of included trials to identify further trials. SELECTION CRITERIA We considered only randomised controlled trials (RCT) performed in people with chronic pancreatic pain due to chronic pancreatitis, irrespective of language, blinding, or publication status for inclusion in the review. DATA COLLECTION AND ANALYSIS Two review authors independently identified trials and independently extracted data. We calculated the risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI) with RevMan 5, based on intention-to-treat analysis. MAIN RESULTS Only one study, funded by Pfizer, met the inclusion criteria for the review. A total of 64 participants (with chronic pain due to chronic pancreatitis) were randomly assigned to receive escalating doses of pregabalin (150 mg per day to 600 mg per day; 34 participants) or matching placebo (30 participants). Participants received pregabalin or placebo for three weeks on an outpatient basis; the outcomes were measured at the end of the treatment (i.e. three weeks from commencement of treatment). Potential participants taking concomitant analgesic medication and expected to stay on a stable regime during the trial were allowed to enter the study. This trial was at low risk of bias. The overall quality of evidence was low or moderate.Only the short-term outcomes were available in this trial. The medium and long-term outcomes, number of work days lost, and length of hospital stay due to admissions for pain control were not available. This trial found that the changes in opiate use (MD -26.00 mg; 95% CI -47.36 to -4.64; participants = 64; moderate-quality evidence), and pain score percentage changes from baseline (MD -12.00; 95% CI -21.82 to -2.18; participants = 64; moderate-quality evidence) were better in participants taking pregabalin compared to those taking placebo. This trial also found that there were more adverse events in participants tak\u2026", "author" : [ { "dropping-particle" : "", "family" : "Gurusamy", "given" : "Kurinchi Selvan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lusuku", "given" : "Charnelle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davidson", "given" : "Brian R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Cochrane database of systematic reviews", "editor" : [ { "dropping-particle" : "", "family" : "Gurusamy", "given" : "Kurinchi Selvan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2016", "2", "2" ] ] }, "note" : "NULL", "page" : "CD011522", "publisher" : "John Wiley & Sons, Ltd", "publisher-place" : "Chichester, UK", "title" : "Pregabalin for decreasing pancreatic pain in chronic pancreatitis.", "type" : "article-journal", "volume" : "2" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(201)", "plainTextFormattedCitation" : "(201)", "previouslyFormattedCitation" : "(201)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(201). Anti-depressive drugs are widely used for pain treatment and although no data exist in CP, their positive effect in patients with neuropathic pain (thought to be prevalent in CP) makes them attractiveADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/gut.2007.146621", "ISSN" : "1468-3288", "PMID" : "18566105", "abstract" : "Pain mechanisms in patients with chronic pancreatitis are incompletely understood and probably multifactorial. Recently, evidence from experimental human pain research has indicated that in many of these patients pain processing in the central nervous system is abnormal and mimics that seen in neuropathic pain disorders. The current review focuses on several lines of evidence supporting this hypothesis. Hence, the spontaneous and postprandial pain in chronic pancreatitis may reflect the characteristic pain features seen in patients with neuropathic pain. Biochemical and histopathological findings in tissues from patients with chronic pancreatitis are similar to those observed in patients with other nerve fibre lesions. Experimental studies have shown that patients with chronic pancreatitis show signs of spinal hyper-excitability counter-balanced by segmental and descending inhibition. Changes in the brain with cortical reorganisation to gut stimulation and increased activity in specific electroencephalographic features characteristic for neuropathic pain are also seen in patients with chronic pancreatitis. Finally, principles involved in the treatment of pancreatic pain have many similarities with those recommended in neuropathic pain disorders. In conclusion, a mechanism-based understanding of pain in chronic pancreatitis may have important implications for the treatment.", "author" : [ { "dropping-particle" : "", "family" : "Drewes", "given" : "A M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Krarup", "given" : "A L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Detlefsen", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Malmstr\u00f8m", "given" : "M-L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dimcevski", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Funch-Jensen", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gut", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2008", "11", "1" ] ] }, "note" : "NULL", "page" : "1616-27", "title" : "Pain in chronic pancreatitis: the role of neuropathic pain mechanisms.", "type" : "article-journal", "volume" : "57" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(202)", "plainTextFormattedCitation" : "(202)", "previouslyFormattedCitation" : "(202)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(202). Tricyclic antidepressants (TCA), selective serotonin reuptake Inhibitors (SSRI) and serotonin–norepinephrine reuptake inhibitors (SNRI) have been used successfully in functional gastrointestinal disorders. It is, however, unclear if they all have direct analgesic effects versus indirect benefit by reducing anxiety and depressionADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/MIB.0000000000000734", "ISSN" : "1536-4844", "PMID" : "27167571", "abstract" : "BACKGROUND The use of psychotropic medications, particularly antidepressants, is common in patients with inflammatory bowel disease (IBD) in spite of a lack of their robust efficacy in this population. This review provides an overview of the use trends of different classes of antidepressant and anti-anxiety medication and their effects on mood, nervous system function, gastrointestinal physiology and immunity drawing from the literature available in the general population, other medical conditions, and when available, patients with IBD. It also covers the evidence base for the actions, efficacy, and potential complications of antidepressants organized by different classes. METHODS We conducted a PubMed search of articles relating the different drug classes probed to the terms above in different populations of interest. All types of articles were accepted including case reports and series, open and randomized trials, reviews, and expert opinion. We also examined the reference lists of the publications found. RESULTS Selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) are the most commonly prescribed agents for anxiety and depression in patients with IBD, though their efficacy for these conditions in the general population are mild to moderate at best. SSRIs are generally well tolerated, though at higher doses, they, like most antidepressant classes, can be associated with activation, serotonergic syndrome, and increased suicidal ideation. TCAs have many more serious side effects but have some shown efficacy for functional GI symptoms. A newer class, the serotonin noradrenergic reuptake inhibitors (SNRIs), can be effective for refractory depression, anxiety and chronic pain syndromes with a side effect profile similar to both SSRIs and more mild manifestations of TCAs. Mirtazapine has moderate efficacy for depression if sedation and weight gain side effects are tolerated and some small support for use in nausea and vomiting. Bupropion targets dopamine and noradrenaline reuptake and has moderate efficacy for depression, and some small support for use in fatigue and smoking cessation. Buspirone has an indication for generalized anxiety disorder though studies show only a minimal benefit. It has some growing evidence for use in functional dyspepsia. Most of these agents have physiological effects on the brain, immune system, and gastrointestinal tract (with the exception of bupropion) hence their therapeutic and side effects \u2026", "author" : [ { "dropping-particle" : "", "family" : "Thorkelson", "given" : "Gregory", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bielefeldt", "given" : "Klaus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Szigethy", "given" : "Eva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Inflammatory bowel diseases", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2016", "6" ] ] }, "note" : "NULL", "page" : "1509-22", "title" : "Empirically Supported Use of Psychiatric Medications in Adolescents and Adults with IBD.", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(203)", "plainTextFormattedCitation" : "(203)", "previouslyFormattedCitation" : "(203)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(203). On the other hand, TCAs appear to have analgesic and neuromodulatory properties that are unrelated to their psychotropic effectsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0127815", "ISSN" : "1932-6203", "PMID" : "26252008", "abstract" : "AIM The aim of this meta-analysis was to analyze the efficacy and safety of antidepressants for the treatment of irritable bowel syndrome. METHODS We searched MEDLINE, EMBASE, Scopus and The Cochrane Library for randomized controlled trials investigating the efficacy and safety of antidepressants in the treatment of irritable bowel syndrome. Article quality was evaluated by Jadad score. RevMan 5.0 and Stata 12.0 were used for the meta-analysis. RESULTS Twelve randomized controlled trials were included in this study and most of these trials were of high quality (Jadad score \u22654). Five articles focused on tricyclic antidepressants, six articles involved selective serotonin reuptake inhibitors, and one article investigated both types of treatment. The pooled risk ratio showed antidepressant treatment can improve global symptoms (RR = 1.38, 95% CI 1.08, 1.77). In the subgroup analysis, treatment with tricyclic antidepressants showed an improvement in global symptoms (RR = 1.36, 95% CI 1.07, 1.71), while treatment with selective serotonin reuptake inhibitors showed no statistically significant difference in global symptoms compared with the control groups (RR = 1.38, 95% CI 0.83, 2.28). The pooled risk ratio of dropout due to side effects following antidepressant treatment was 1.71 with 95% CI (0.98, 2.99). The subgroup analysis showed the pooled risk ratio of dropout in the tricyclic antidepressants group was 1.92 with 95% CI (0.89, 4.17). In the selective serotonin reuptake inhibitors group, the pooled risk ratio of dropout was 1.5 with 95% CI (0.67, 3.37). Selective serotonin reuptake inhibitors showed no benefit in alleviating abdominal pain and improving quality of life. There was no difference in the incidence of common adverse events between treatment and control groups. CONCLUSIONS TCAs can improve global symptoms of irritable bowel syndrome, while there was no strong evidence to confirm the effectiveness of SSRIs for the treatment of IBS.", "author" : [ { "dropping-particle" : "", "family" : "Xie", "given" : "Chen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tang", "given" : "Yurong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Yunfeng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yu", "given" : "Ting", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Yun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jiang", "given" : "Liuqin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lin", "given" : "Lin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLOS ONE", "editor" : [ { "dropping-particle" : "", "family" : "Lu", "given" : "Lin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2015", "8", "7" ] ] }, "note" : "NULL", "page" : "e0127815", "title" : "Efficacy and Safety of Antidepressants for the Treatment of Irritable Bowel Syndrome: A Meta-Analysis", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1038/ajg.2014.187", "ISSN" : "1572-0241", "PMID" : "25091148", "author" : [ { "dropping-particle" : "", "family" : "Ford", "given" : "Alexander C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moayyedi", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lacy", "given" : "Brian E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lembo", "given" : "Anthony J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saito", "given" : "Yuri A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schiller", "given" : "Lawrence R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Soffer", "given" : "Edy E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spiegel", "given" : "Brennan M R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Quigley", "given" : "Eamonn M M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Task Force on the Management of Functional Bowel Disorders", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American journal of gastroenterology", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2014", "8" ] ] }, "note" : "NULL", "page" : "S2-26; quiz S27", "title" : "American College of Gastroenterology monograph on the management of irritable bowel syndrome and chronic idiopathic constipation.", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(204,205)", "plainTextFormattedCitation" : "(204,205)", "previouslyFormattedCitation" : "(204,205)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(204,205). It is important to start at very low doses and titrate slowly over weeks as side effects such as cardiovascular can be dose-limitingADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.amjmed.2011.08.026", "ISSN" : "1555-7162", "PMID" : "22444104", "abstract" : "OBJECTIVE Current treatment options for irritable bowel syndrome are limited and often poorly studied. A select few drugs have been studied in irritable bowel syndrome, and the number needed to treat is frequently used to assess the relative efficacy of these treatments. However, side effects are an important consideration in the clinical decision on which particular treatment to use. This study examines trials of subjects with irritable bowel syndrome with diarrhea and constipation who are receiving a drug intervention deemed of merit by the American College of Gastroenterology task force and compares these therapies to examine the number needed to harm using a systematic review and meta-analysis approach. METHODS Potential studies of irritable bowel syndrome treatments were identified through a search of MEDLINE (1950 to April 2011), EMBASE (1980 to April 2011), the Cochrane central register of controlled trials, and the bibliography of recent meta-analyses. Clinical trials of pharmacotherapy for irritable bowel syndrome were eligible for inclusion only if a description of adverse events and the number of patients who discontinued treatment because of adverse events were reported. The relative risk of experiencing an adverse event requiring discontinuation of treatment was used to determine the number needed to harm. In addition, the number and severity of adverse events were summarized. RESULTS Twenty-six clinical trials (4 with selective serotonin reuptake inhibitors, 3 with lubiprostone, 6 with tricyclic antidepressants, 8 with alosetron, and 5 with rifaximin) were included. Lubiprostone was safe with insignificant harm in one combined phase III trial. Selective serotonin reuptake inhibitors did not have enough data for a reliable meta-analysis of harm but seemed to be safe. More rigorous data were available for tricyclic antidepressants, alosetron, and rifaximin; the numbers needed to harm were 18.3, 19.4, and 8971, respectively, and the numbers needed to treat were 8, 7.5, and 10.6, respectively. For tricyclic antidepressant and alosetron, an adverse event resulting in discontinuation of the study medication occurred for every 2.3 and 2.6 patients who benefited from a drug, respectively. For rifaximin, this number was 846 patients. In addition, adverse events were more common with tricyclic antidepressants and alosetron. CONCLUSION In irritable bowel syndrome with diarrhea, tricyclic antidepressants and alosetron are associated with a significant\u2026", "author" : [ { "dropping-particle" : "", "family" : "Shah", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Sharon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chong", "given" : "Kelly", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lembo", "given" : "Anthony", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pimentel", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American journal of medicine", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2012", "4" ] ] }, "note" : "NULL", "page" : "381-93", "title" : "Evaluation of harm in the pharmacotherapy of irritable bowel syndrome.", "type" : "article-journal", "volume" : "125" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(206)", "plainTextFormattedCitation" : "(206)", "previouslyFormattedCitation" : "(206)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(206). It should be noted that there are major differences in receptor properties and analgesic mechanisms between the different TCA and SSRI/SNRIs and therefore an individual approach is necessary. Due to the sedative effects a single dose at night-time may be preferable. Unfortunately, clinical experience indicates that the side effect profile often makes them less suitable in patients with CP. For further reading, see T?rnblom et al. 2015ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/nmo.12509", "ISSN" : "1365-2982", "PMID" : "25651186", "abstract" : "BACKGROUND Chronic abdominal pain in the context of the functional gastrointestinal disorders departs from a more traditional approach to treating gastrointestinal symptoms. Chronic abdominal pain involves a dysregulation of brain-gut modulation of afferent signaling, so treatments directed toward the gut are not usually sufficient to achieve a clinical response. Rather the methods of treatment depend on re-establishing central pain regulation. PURPOSE A conceptual model of predisposing, precipitating, and perpetuating factors is used to explain how a situation of chronic pain develops and it provides the evidence for central neuron degeneration as relevant to this chain of events. The rationale for centrally targeted medications, in particular antidepressants, is discussed with regard to effects independent of their role in treating psychiatric disorders: with regard to downregulation of afferent pain signals and their potential role in neuron proliferation. Finally, guiding examples of which drug to use and treatment combinations involving multiple drugs, augmentation treatment, are outlined and some brief clinical cases of centrally targeted pharmacotherapy.", "author" : [ { "dropping-particle" : "", "family" : "T\u00f6rnblom", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drossman", "given" : "D A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2015", "4" ] ] }, "note" : "NULL", "page" : "455-67", "title" : "Centrally targeted pharmacotherapy for chronic abdominal pain.", "type" : "article-journal", "volume" : "27" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(207)", "plainTextFormattedCitation" : "(207)", "previouslyFormattedCitation" : "(207)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(207) and Scottish Intercollegiate Guidelines NetworkADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/nmo.12509", "ISSN" : "1365-2982", "PMID" : "25651186", "abstract" : "BACKGROUND Chronic abdominal pain in the context of the functional gastrointestinal disorders departs from a more traditional approach to treating gastrointestinal symptoms. Chronic abdominal pain involves a dysregulation of brain-gut modulation of afferent signaling, so treatments directed toward the gut are not usually sufficient to achieve a clinical response. Rather the methods of treatment depend on re-establishing central pain regulation. PURPOSE A conceptual model of predisposing, precipitating, and perpetuating factors is used to explain how a situation of chronic pain develops and it provides the evidence for central neuron degeneration as relevant to this chain of events. The rationale for centrally targeted medications, in particular antidepressants, is discussed with regard to effects independent of their role in treating psychiatric disorders: with regard to downregulation of afferent pain signals and their potential role in neuron proliferation. Finally, guiding examples of which drug to use and treatment combinations involving multiple drugs, augmentation treatment, are outlined and some brief clinical cases of centrally targeted pharmacotherapy.", "author" : [ { "dropping-particle" : "", "family" : "T\u00f6rnblom", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drossman", "given" : "D A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2015", "4" ] ] }, "note" : "NULL", "page" : "455-67", "title" : "Centrally targeted pharmacotherapy for chronic abdominal pain.", "type" : "article-journal", "volume" : "27" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(207)", "plainTextFormattedCitation" : "(207)", "previouslyFormattedCitation" : "(207)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(207).Opioid analgesics are indispensable for the management of painADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3109/15360288.2011.599485", "ISSN" : "1536-0288", "PMID" : "21882978", "abstract" : "In 2011, the World Health Organization (WHO) published a series of 21 guidelines to assist governments in improving their national drug control laws, regulations, and administrative procedures to promote the availability of controlled medicines for pain relief and for a variety of acute and chronic diseases and conditions. These guidelines ultimately are designed to encourage the development of policies designed to fulfill a country's dual obligation concerning these medicines: to prevent their abuse, diversion and trafficking while ensuring access for medical and scientific purposes. This article summarizes each guideline and outlines the constituents who can actively participate in making controlled medicines available to the patients who need them. It is hoped that representatives of governments and medical institutions, as well as health care professionals, will commonly and effectively use the revised WHO guidelines as a policy change tool.", "author" : [ { "dropping-particle" : "", "family" : "Gilson", "given" : "Aaron M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maurer", "given" : "Martha A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ryan", "given" : "Karen M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Skemp-Brown", "given" : "Marty", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Husain", "given" : "Asra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cleary", "given" : "James F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Pain & Palliative Care Pharmacotherapy", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2011", "8", "30" ] ] }, "note" : "NULL", "page" : "246-251", "title" : "Ensuring Patient Access to Essential Medicines While Minimizing Harmful Use: A Revised World Health Organization Tool to Improve National Drug Control Policy", "type" : "article-journal", "volume" : "25" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(208)", "plainTextFormattedCitation" : "(208)", "previouslyFormattedCitation" : "(208)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(208), but therapy should only be initiated when more simple strategies have failed following a reasonable trial periodADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1001/jama.2016.1464", "ISSN" : "0098-7484", "author" : [ { "dropping-particle" : "", "family" : "Dowell", "given" : "Deborah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haegerich", "given" : "Tamara M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chou", "given" : "Roger", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "JAMA", "id" : "ITEM-1", "issue" : "15", "issued" : { "date-parts" : [ [ "2016", "4", "19" ] ] }, "note" : "NULL", "page" : "1624", "title" : "CDC Guideline for Prescribing Opioids for Chronic Pain\u2014United States, 2016", "type" : "article-journal", "volume" : "315" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(209)", "plainTextFormattedCitation" : "(209)", "previouslyFormattedCitation" : "(209)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(209). Opioids are highly effective and safe analgesics and their appropriate use by competent clinicians is a crucial element in modern pain management. However, treatment is often complicated by severe adverse effects and may lead to addiction. Furthermore, some opioids like codeine, tramadol and morphine are contraindicated or require prolonged dose intervals in patients with severe renal and hepatic insufficiency, which is not uncommon in CP. While not studied in CP, patients who have chronic pain and opioid use disorders may benefit from partial opioid antagonists such as buprenorphine, though randomized controlled trials are not availableADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.4088/JCP.15m09893", "ISSN" : "1555-2101", "PMID" : "27035058", "abstract" : "OBJECTIVE Posttraumatic stress disorder (PTSD), chronic pain, and substance use disorders are prevalent co-occurring conditions that are challenging to treat individually, and there is no evidence-based treatment for all 3. Buprenorphine, used to treat opioid use disorder and chronic pain, is a partial nociceptin opioid receptor agonist. In preclinical studies, a nociceptin opioid receptor agonist was shown to mitigate PTSD symptoms in acute trauma. We compared buprenorphine to other opioid medications in its impact on PTSD symptoms in patients with chronic pain and opioid and/or other substance use disorders. METHOD We assembled a retrospective cohort of 382 Iraq and Afghanistan veterans in US Department of Veterans Affairs health care from October 1, 2007, to July 29, 2013, with ICD-9-CM diagnoses of PTSD, chronic pain, and substance use disorders. We used time-varying general estimating equation models to assess the primary outcome, which was change in PTSD symptoms (measured using the PTSD Checklist and the Primary Care PTSD Screen) among veterans initiated on sublingual buprenorphine versus those maintained on moderately high-dose opioid therapy. RESULTS Twice as many veterans in the buprenorphine group (23.7%) compared to those in the opioid therapy group (11.7%) experienced improvement in PTSD symptoms (P = .001). Compared to veterans in the opioid therapy group, veterans receiving buprenorphine showed significant improvement in PTSD symptoms after 8 months, with increasing improvement up to 24 months (incidence rate ratio = 1.79; 95% CI, 1.16-2.77; P = .009). There were no differences in the longitudinal course of pain ratings between groups. CONCLUSIONS This observational study is the first to report an incidental effect of buprenorphine compared to opioid therapy in improving PTSD symptoms in veterans.", "author" : [ { "dropping-particle" : "", "family" : "Seal", "given" : "Karen H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maguen", "given" : "Shira", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bertenthal", "given" : "Daniel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Batki", "given" : "Steven L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Striebel", "given" : "Joan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stein", "given" : "Murray B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Madden", "given" : "Erin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Neylan", "given" : "Thomas C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of clinical psychiatry", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2016", "9", "28" ] ] }, "note" : "NULL", "page" : "1182-1188", "title" : "Observational Evidence for Buprenorphine's Impact on Posttraumatic Stress Symptoms in Veterans With Chronic Pain and Opioid Use Disorder.", "type" : "article-journal", "volume" : "77" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.clinthera.2006.06.012", "ISSN" : "0149-2918", "PMID" : "16860176", "abstract" : "BACKGROUND Transdermal buprenorphine is available in Europe for the treatment of moderate to severe chronic pain. It has been evaluated at doses of 35, 52.5, and 70 microg/h for the management of moderate to severe chronic cancer and noncancer pain in 3 randomized, double-blind, placebo-controlled trials, each of limited duration (approximately 14 days each). Long-term data are essential to determining the performance of an analgesic in the management of chronic pain. OBJECTIVE The purpose of this follow-up study was to obtain data on the efficacy and tolerability of long-term treatment with transdermal buprenorphine in cancer and noncancer patients with chronic persistent pain of moderate to severe intensity. METHODS This was an open-label, uncontrolled, follow-up study in patients from the 3 previous clinical trials who elected to continue treatment with transdermal buprenorphine 35 microg/h and sublingual buprenorphine tablets (0.2 mg) as needed for breakthrough pain. The patch was to be changed every 72 hours throughout the patient's course of pain therapy. At visits every 2 weeks for the first 4 weeks and every 4 weeks for the remainder of study participation, patients evaluated their pain relief retrospectively on a 4-point verbal rating scale. They also rated the ease of patch handling using a 3-point verbal rating scale. Patterns of dose escalation and dose stability were monitored over time. Adherence to therapy was determined based on the number of patients who complied with the dosing schedule. Adverse events were documented by type, intensity, location (systemic or local), and relationship to study medication. RESULTS Two hundred thirty-nine patients were included in this follow-up study (120 women, 119 men; 100% white; mean [SD] age, 58 [11.3] years; mean weight, 70.8 [14.7] kg). One hundred thirty-four had cancer-related pain and 105 had pain of noncancerous origin. The mean duration of participation was 7.5 months, and 37 (15.5%) patients participated for >12 months. Maximum study participation was 3.4 years in cancer patients and 5.7 years in noncancer patients. One hundred eighty-eight (78.7%) patients were considered adherent to therapy. The majority (65.9%) of patients managed their pain with the patchalone or took no more than 1 additional sublingual tablet daily for breakthrough pain. At least satisfactory pain relief was reported by 215 (90.0%) patients, and the buprenorphine patch was generally well tolerated. The most common syst\u2026", "author" : [ { "dropping-particle" : "", "family" : "Likar", "given" : "Rudolf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kayser", "given" : "Hubertus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sittl", "given" : "Reinhard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical therapeutics", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2006", "6" ] ] }, "note" : "NULL", "page" : "943-52", "title" : "Long-term management of chronic pain with transdermal buprenorphine: a multicenter, open-label, follow-up study in patients from three short-term clinical trials.", "type" : "article-journal", "volume" : "28" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(210,211)", "plainTextFormattedCitation" : "(210,211)", "previouslyFormattedCitation" : "(210,211)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(210,211). Opioids should not be used in isolation, but form part of a multi-faceted strategy that includes all necessary adjuvant analgesics, non-drug interventions, psychological support and rehabilitation. There are enormous variations in opioid use across the globe, and even within close regions major variations are observedADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1365-2125.2012.04317.x", "ISSN" : "1365-2125", "PMID" : "22554450", "abstract" : "Clinical studies comparing the response and side effects of various opioids have not been able to show robust differences between drugs. Hence, recommendations of the regulatory authorities have been driven by costs with a general tendency in many countries to restrict physician's use of opioids to morphine. Although this approach is recognized as cost-effective in most cases there is solid evidence that, on an individual patient basis, opioids are not all equal. Therefore it is important to have an armamentarium of strong analgesics in clinical practice to ensure a personalized approach in patients who do not respond to standard treatment. In this review we highlight differences between opioids in human studies from a pharmacological, experimental, clinical and health economics point of view. We provide evidence that individuals respond differently to opioids, and that general differences between classes of opioids exist. We recommend that this recognition is used to individualize treatment in difficult cases allowing physicians to have a wide range of treatment options. In the end this will reduce pain and side effects, leading to improved quality of life for the patient and reduce the exploding pain related costs.", "author" : [ { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jensen", "given" : "Rasmus D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nielsen", "given" : "Lecia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Droney", "given" : "Joanne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Christrup", "given" : "Lona L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arendt-Nielsen", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Riley", "given" : "Julia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dahan", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "British journal of clinical pharmacology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2013", "1" ] ] }, "note" : "From Duplicate 1 (Differences between opioids: pharmacological, experimental, clinical and economical perspectives. - Drewes, Asbj\u00f8rn M; Jensen, Rasmus D; Nielsen, Lecia M; Droney, Joanne; Christrup, Lona L; Arendt-Nielsen, Lars; Riley, Julia; Dahan, Albert)\n\nNULL", "page" : "60-78", "title" : "Differences between opioids: pharmacological, experimental, clinical and economical perspectives.", "type" : "article-journal", "volume" : "75" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(212)", "plainTextFormattedCitation" : "(212)", "previouslyFormattedCitation" : "(212)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(212). This is based partly on local traditions, partly on regulatory matters and to some degree by “opiophobia” and will not be the discussed further in this section. As opioid use seems to be a necessary step to dampen pain in many patients with CP it is mandatory that pancreatologists understand the complexity of opioid treatment, or alternatively treat patients in close collaboration with dedicated pain specialists. Of note, all patients must be fully educated on the proposed therapeutic strategy and informed about the risks for addiction and side effects especially opioid induced bowel dysfunction, emesis and affection of the central nervous system. In some cases the pain increases despite increased dose and in such situations opioid induced bowel dysfunction or opioid induced hyperalgesia (narcotic bowel syndrome) should be suspected as it may mimic the pain in CP. For details, see Drewes et al. 2016 and Drossman and Szigethy 2014ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.sjpain.2015.12.005", "ISSN" : "18778860", "author" : [ { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Munkholm", "given" : "Pia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Simr\u00e9n", "given" : "Magnus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Breivik", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kongsgaard", "given" : "Ulf E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hatlebakk", "given" : "Jan G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Agreus", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Friedrichsen", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Christrup", "given" : "Lona L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian Journal of Pain", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2016", "4" ] ] }, "page" : "111-122", "title" : "Definition, diagnosis and treatment strategies for opioid-induced bowel dysfunction\u2014Recommendations of the Nordic Working Group", "type" : "article-journal", "volume" : "11" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1038/ajgsup.2014.6", "ISSN" : "1948-9501", "PMID" : "25207609", "abstract" : "OBJECTIVES The paradoxical development of chronic abdominal pain is an underrecognized side effect of opioid use. Narcotic bowel syndrome (NBS), occurring in a small proportion of chronic opioid users, consists of chronic or intermittent abdominal pain, which often increases in severity despite continued or escalating dosages of opioids prescribed to relieve pain. METHODS A PubMed search was conducted using terms such as \"narcotic bowel syndrome\" and \"opioid hyperalgesia\" through January 2014. RESULTS Abdominal pain is the defining symptom of NBS and is thought to be mediated by central nervous system dysfunction; it should be distinguished from the peripheral side effects of opioids, such as nausea, bloating, intermittent vomiting, abdominal distension, and constipation. This latter cluster of symptoms is called opioid bowel dysfunction, although it may co-occur with NBS. Hypothesized mechanisms of the central effects of opioids on nociception in NBS include spinal cord inflammation and dysfunction in opioid receptor activity and related neuroanatomical substrates. With continued use, \u223c6% of patients taking narcotics chronically will develop NBS, with profound consequences in terms of daily function. The primary management paradigm for NBS is a structured opioid withdrawal program accompanied by centrally acting adjunctive therapy comprising antidepressants, benzodiazepines, and clonidine to target pain, anxiety, and depression, and prevent withdrawal effects, in addition to peripherally acting agents such as laxatives (e.g., osmotic laxatives and chloride channel activators) to control transient constipation. Such structured withdrawal programs have been prospectively evaluated in small clinical trials and have met with considerable success in the short term. CONCLUSIONS Because rates of NBS are likely to rise, integrated intensive pharmacotherapy and psychosocial interventions are needed to help patients with NBS go off and stay off opioids. These programs will likely also reduce comorbid psychopathology and lead to adequate pain control and improved quality of life.", "author" : [ { "dropping-particle" : "", "family" : "Drossman", "given" : "Douglas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Szigethy", "given" : "Eva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American journal of gastroenterology supplements (Print)", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2014", "9", "10" ] ] }, "note" : "NULL", "page" : "22-30", "title" : "The narcotic bowel syndrome: a recent update.", "type" : "article-journal", "volume" : "2" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(213,214)", "plainTextFormattedCitation" : "(213,214)", "previouslyFormattedCitation" : "(213,214)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(213,214). Treatment may include increased use of laxatives, opioid antagonists with restricted effect on the gut, tapentadol or in case of hyperalgesia tapering of opioidsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1177/1756283X15589526", "ISSN" : "1756-283X", "PMID" : "26557892", "abstract" : "In recent years prescription of opioids has increased significantly. Although effective in pain management, bothersome gastrointestinal adverse effects are experienced by a substantial proportion of opioid-treated patients. This can lead to difficulties with therapy and subsequently inadequate pain relief. Collectively referred to as opioid-induced bowel dysfunction, these adverse effects are the result of binding of exogenous opioids to opioid receptors in the gastrointestinal tract. This leads to disturbance of three important gastrointestinal functions: motility, coordination of sphincter function and secretion. In the clinic this manifests in a wide range of symptoms such as reflux, bloating, abdominal cramping, hard, dry stools, and incomplete evacuation, although the most known adverse effect is opioid-induced constipation. Traditional treatment with laxatives is often insufficient, but in recent years a number of novel pharmacological approaches have been introduced. In this review the pathophysiology, symptomatology and prevalence of opioid-induced bowel dysfunction is presented along with the benefits and caveats of a suggested consensus definition for opioid-induced constipation. Finally, traditional treatment is appraised and compared with the latest pharmacological developments. In conclusion, opioid antagonists restricted to the periphery show promising results, but use of different definitions and outcome measures complicate comparison. However, an international working group has recently suggested a consensus definition for opioid-induced constipation and relevant outcome measures have also been proposed. If investigators within this field adapt the suggested consensus and include symptoms related to dysfunction of the upper gut, it will ease comparison and be a step forward in future research.", "author" : [ { "dropping-particle" : "", "family" : "Poulsen", "given" : "Jakob Lykke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brock", "given" : "Christina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olesen", "given" : "Anne Estrup", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nilsson", "given" : "Matias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn Mohr", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Therapeutic advances in gastroenterology", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2015", "11" ] ] }, "note" : "NULL", "page" : "360-72", "title" : "Evolving paradigms in the treatment of opioid-induced bowel dysfunction.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1038/ajgsup.2014.6", "ISSN" : "1948-9501", "PMID" : "25207609", "abstract" : "OBJECTIVES The paradoxical development of chronic abdominal pain is an underrecognized side effect of opioid use. Narcotic bowel syndrome (NBS), occurring in a small proportion of chronic opioid users, consists of chronic or intermittent abdominal pain, which often increases in severity despite continued or escalating dosages of opioids prescribed to relieve pain. METHODS A PubMed search was conducted using terms such as \"narcotic bowel syndrome\" and \"opioid hyperalgesia\" through January 2014. RESULTS Abdominal pain is the defining symptom of NBS and is thought to be mediated by central nervous system dysfunction; it should be distinguished from the peripheral side effects of opioids, such as nausea, bloating, intermittent vomiting, abdominal distension, and constipation. This latter cluster of symptoms is called opioid bowel dysfunction, although it may co-occur with NBS. Hypothesized mechanisms of the central effects of opioids on nociception in NBS include spinal cord inflammation and dysfunction in opioid receptor activity and related neuroanatomical substrates. With continued use, \u223c6% of patients taking narcotics chronically will develop NBS, with profound consequences in terms of daily function. The primary management paradigm for NBS is a structured opioid withdrawal program accompanied by centrally acting adjunctive therapy comprising antidepressants, benzodiazepines, and clonidine to target pain, anxiety, and depression, and prevent withdrawal effects, in addition to peripherally acting agents such as laxatives (e.g., osmotic laxatives and chloride channel activators) to control transient constipation. Such structured withdrawal programs have been prospectively evaluated in small clinical trials and have met with considerable success in the short term. CONCLUSIONS Because rates of NBS are likely to rise, integrated intensive pharmacotherapy and psychosocial interventions are needed to help patients with NBS go off and stay off opioids. These programs will likely also reduce comorbid psychopathology and lead to adequate pain control and improved quality of life.", "author" : [ { "dropping-particle" : "", "family" : "Drossman", "given" : "Douglas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Szigethy", "given" : "Eva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American journal of gastroenterology supplements (Print)", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2014", "9", "10" ] ] }, "note" : "NULL", "page" : "22-30", "title" : "The narcotic bowel syndrome: a recent update.", "type" : "article-journal", "volume" : "2" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(214,215)", "plainTextFormattedCitation" : "(214,215)", "previouslyFormattedCitation" : "(214,215)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(214,215). Patients on long-term opioid therapy must be kept under close clinical surveillance and it shall be stressed that only about 25% of patients benefit from treatment. After 6 months of opioid therapy, a dose reduction (or “drug holiday”) should be considered and discussed with the patientsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1365-2125.2012.04317.x", "ISSN" : "1365-2125", "PMID" : "22554450", "abstract" : "Clinical studies comparing the response and side effects of various opioids have not been able to show robust differences between drugs. Hence, recommendations of the regulatory authorities have been driven by costs with a general tendency in many countries to restrict physician's use of opioids to morphine. Although this approach is recognized as cost-effective in most cases there is solid evidence that, on an individual patient basis, opioids are not all equal. Therefore it is important to have an armamentarium of strong analgesics in clinical practice to ensure a personalized approach in patients who do not respond to standard treatment. In this review we highlight differences between opioids in human studies from a pharmacological, experimental, clinical and health economics point of view. We provide evidence that individuals respond differently to opioids, and that general differences between classes of opioids exist. We recommend that this recognition is used to individualize treatment in difficult cases allowing physicians to have a wide range of treatment options. In the end this will reduce pain and side effects, leading to improved quality of life for the patient and reduce the exploding pain related costs.", "author" : [ { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jensen", "given" : "Rasmus D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nielsen", "given" : "Lecia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Droney", "given" : "Joanne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Christrup", "given" : "Lona L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arendt-Nielsen", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Riley", "given" : "Julia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dahan", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "British journal of clinical pharmacology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2013", "1" ] ] }, "note" : "From Duplicate 1 (Differences between opioids: pharmacological, experimental, clinical and economical perspectives. - Drewes, Asbj\u00f8rn M; Jensen, Rasmus D; Nielsen, Lecia M; Droney, Joanne; Christrup, Lona L; Arendt-Nielsen, Lars; Riley, Julia; Dahan, Albert)\n\nNULL", "page" : "60-78", "title" : "Differences between opioids: pharmacological, experimental, clinical and economical perspectives.", "type" : "article-journal", "volume" : "75" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1001/jama.2016.1464", "ISSN" : "1538-3598", "PMID" : "26977696", "abstract" : "IMPORTANCE Primary care clinicians find managing chronic pain challenging. Evidence of long-term efficacy of opioids for chronic pain is limited. Opioid use is associated with serious risks, including opioid use disorder and overdose. OBJECTIVE To provide recommendations about opioid prescribing for primary care clinicians treating adult patients with chronic pain outside of active cancer treatment, palliative care, and end-of-life care. PROCESS The Centers for Disease Control and Prevention (CDC) updated a 2014 systematic review on effectiveness and risks of opioids and conducted a supplemental review on benefits and harms, values and preferences, and costs. CDC used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework to assess evidence type and determine the recommendation category. EVIDENCE SYNTHESIS Evidence consisted of observational studies or randomized clinical trials with notable limitations, characterized as low quality using GRADE methodology. Meta-analysis was not attempted due to the limited number of studies, variability in study designs and clinical heterogeneity, and methodological shortcomings of studies. No study evaluated long-term (\u22651 year) benefit of opioids for chronic pain. Opioids were associated with increased risks, including opioid use disorder, overdose, and death, with dose-dependent effects. RECOMMENDATIONS There are 12 recommendations. Of primary importance, nonopioid therapy is preferred for treatment of chronic pain. Opioids should be used only when benefits for pain and function are expected to outweigh risks. Before starting opioids, clinicians should establish treatment goals with patients and consider how opioids will be discontinued if benefits do not outweigh risks. When opioids are used, clinicians should prescribe the lowest effective dosage, carefully reassess benefits and risks when considering increasing dosage to 50 morphine milligram equivalents or more per day, and avoid concurrent opioids and benzodiazepines whenever possible. Clinicians should evaluate benefits and harms of continued opioid therapy with patients every 3 months or more frequently and review prescription drug monitoring program data, when available, for high-risk combinations or dosages. For patients with opioid use disorder, clinicians should offer or arrange evidence-based treatment, such as medication-assisted treatment with buprenorphine or methadone. CONCLUSIONS AND RELEVANCE The guideline is intend\u2026", "author" : [ { "dropping-particle" : "", "family" : "Dowell", "given" : "Deborah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haegerich", "given" : "Tamara M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chou", "given" : "Roger", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "JAMA", "id" : "ITEM-2", "issue" : "15", "issued" : { "date-parts" : [ [ "2016", "4", "19" ] ] }, "note" : "NULL", "page" : "1624-45", "title" : "CDC Guideline for Prescribing Opioids for Chronic Pain--United States, 2016.", "type" : "article-journal", "volume" : "315" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(212,216)", "plainTextFormattedCitation" : "(212,216)", "previouslyFormattedCitation" : "(212,216)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(212,216). For further information the reader is referred to e.g. Dowell et al. 2016)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1001/jama.2016.1464", "ISSN" : "1538-3598", "PMID" : "26977696", "abstract" : "IMPORTANCE Primary care clinicians find managing chronic pain challenging. Evidence of long-term efficacy of opioids for chronic pain is limited. Opioid use is associated with serious risks, including opioid use disorder and overdose. OBJECTIVE To provide recommendations about opioid prescribing for primary care clinicians treating adult patients with chronic pain outside of active cancer treatment, palliative care, and end-of-life care. PROCESS The Centers for Disease Control and Prevention (CDC) updated a 2014 systematic review on effectiveness and risks of opioids and conducted a supplemental review on benefits and harms, values and preferences, and costs. CDC used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework to assess evidence type and determine the recommendation category. EVIDENCE SYNTHESIS Evidence consisted of observational studies or randomized clinical trials with notable limitations, characterized as low quality using GRADE methodology. Meta-analysis was not attempted due to the limited number of studies, variability in study designs and clinical heterogeneity, and methodological shortcomings of studies. No study evaluated long-term (\u22651 year) benefit of opioids for chronic pain. Opioids were associated with increased risks, including opioid use disorder, overdose, and death, with dose-dependent effects. RECOMMENDATIONS There are 12 recommendations. Of primary importance, nonopioid therapy is preferred for treatment of chronic pain. Opioids should be used only when benefits for pain and function are expected to outweigh risks. Before starting opioids, clinicians should establish treatment goals with patients and consider how opioids will be discontinued if benefits do not outweigh risks. When opioids are used, clinicians should prescribe the lowest effective dosage, carefully reassess benefits and risks when considering increasing dosage to 50 morphine milligram equivalents or more per day, and avoid concurrent opioids and benzodiazepines whenever possible. Clinicians should evaluate benefits and harms of continued opioid therapy with patients every 3 months or more frequently and review prescription drug monitoring program data, when available, for high-risk combinations or dosages. For patients with opioid use disorder, clinicians should offer or arrange evidence-based treatment, such as medication-assisted treatment with buprenorphine or methadone. CONCLUSIONS AND RELEVANCE The guideline is intend\u2026", "author" : [ { "dropping-particle" : "", "family" : "Dowell", "given" : "Deborah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haegerich", "given" : "Tamara M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chou", "given" : "Roger", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "JAMA", "id" : "ITEM-1", "issue" : "15", "issued" : { "date-parts" : [ [ "2016", "4", "19" ] ] }, "note" : "NULL", "page" : "1624-45", "title" : "CDC Guideline for Prescribing Opioids for Chronic Pain--United States, 2016.", "type" : "article-journal", "volume" : "315" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(216)", "plainTextFormattedCitation" : "(216)", "previouslyFormattedCitation" : "(216)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(216)Codeine is a weak opioid in level II analgesia, but it is metabolized to morphine and therefore associated with the same spectrum of opioid-related side effects as seen for stronger opioids. Tramadol possesses both a weak opioid agonist activity along with an effect on noradrenaline and serotonin uptakeADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3748/wjg.v19.i42.7292", "ISSN" : "1007-9327", "PMID" : "24259960", "abstract" : "Intense abdominal pain is a prominent feature of chronic pancreatitis and its treatment remains a major clinical challenge. Basic studies of pancreatic nerves and experimental human pain research have provided evidence that pain processing is abnormal in these patients and in many cases resembles that seen in neuropathic and chronic pain disorders. An important ultimate outcome of such aberrant pain processing is that once the disease has advanced and the pathophysiological processes are firmly established, the generation of pain can become self-perpetuating and independent of the initial peripheral nociceptive drive. Consequently, the management of pain by traditional methods based on nociceptive deafferentation (e.g., surgery and visceral nerve blockade) becomes difficult and often ineffective. This novel and improved understanding of pain aetiology requires a paradigm shift in pain management of chronic pancreatitis. Modern mechanism based pain treatments taking into account altered pain processing are likely to increasingly replace invasive therapies targeting the nociceptive source, which should be reserved for special and carefully selected cases. In this review, we offer an overview of the current available pharmacological options for pain management in chronic pancreatitis. In addition, future options for pain management are discussed with special emphasis on personalized pain medicine and multidisciplinarity.", "author" : [ { "dropping-particle" : "", "family" : "Olesen", "given" : "S\u00f8ren S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Juel", "given" : "Jacob", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graversen", "given" : "Carina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kolesnikov", "given" : "Yuri", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "Oliver H G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "World Journal of Gastroenterology", "id" : "ITEM-1", "issue" : "42", "issued" : { "date-parts" : [ [ "2013", "11", "14" ] ] }, "note" : "NULL", "page" : "7292", "title" : "Pharmacological pain management in chronic pancreatitis", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(217)", "plainTextFormattedCitation" : "(217)", "previouslyFormattedCitation" : "(217)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(217). Tramadol is often the preferred level II analgesia and was shown to be superior to morphine in patients with CP, with fewer gastrointestinal side effects for the same level of analgesia ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0163-2116", "PMID" : "10389680", "abstract" : "Tramadol and morphine were compared for treatment of severe chronic pancreatitis pain and their interaction with gut motor function. Oral tramadol or morphine doses were titrated double-blinded and randomized for five days in 25 patients and pain, side effects, bowel function, orocecal and colonic transit, anal resting pressure, and rectal distension thresholds were measured. Pain intensities (mean+/-SD, 0 = none, 100 = unbearable) before treatment and on day 4 were 75+/-19 and 8+/-13 with tramadol (P < 0.001), and 65+/-21 and 5+/-6 with morphine (P < 0.001). On day 4, 67% of patients with tramadol and 20% with morphine rated their analgesia as excellent (P < 0.001) with mean respective doses of 840 mg (range: 80-1920) and 238 mg (20-1125). Orocecal transit was unchanged after five days of tramadol, but increased with morphine (P < 0.05). More patients had prolonged colonic transit times with morphine by day 5 (P < 0.05). Rectal distension threshold pressures increased only with tramadol (P < 0.01). It is concluded tramadol and morphine are potent analgesics in severe chronic pancreatitis pain when individually titrated. Tramadol interfered significantly less with gastrointestinal function and was more often rated as an excellent analgesic than morphine.", "author" : [ { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "C H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hill", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Osler", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Keefe", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Digestive diseases and sciences", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "1999", "6" ] ] }, "note" : "NULL", "page" : "1107-16", "title" : "Effect of tramadol and morphine on pain and gastrointestinal motor function in patients with chronic pancreatitis.", "type" : "article-journal", "volume" : "44" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(218)", "plainTextFormattedCitation" : "(218)", "previouslyFormattedCitation" : "(218)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(218). Level III analgesia comprises the group of strong opioids such as morphine, which are widely used for pain in CP. Most clinical available opioids have their activity at the μ-receptor, but preclinical and experimental studies suggest that activation of the κ-receptor (another opioid receptor activated by e.g. oxycodone) may also be important in visceral pain including pain in CPADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0016-5085", "PMID" : "8831591", "abstract" : "BACKGROUND & AIMS Discomfort and pain are the principal conscious sensations that arise from the viscera, and both are increased in frequency and intensity in patients with a functional bowel disorder. Visceral receptors, perhaps sensitized, may contribute to these altered sensations. The aim of this study was to evaluate the effects of opioid receptor-selective agonists on afferent fibers innervating the colon. METHODS Mechanosensitive pelvic nerve afferent fibers were recorded from the decentralized S1 dorsal root in anesthetized rats. The effects of opioid agonists, given intra-arterially, were studied based on the fiber's responses to noxious colorectal distention (CRD) (80 mm Hg, 30 seconds). RESULTS A total of 115 distention-sensitive fibers innervating the colon were studied, including 32 that were studied after colonic inflammation with 2.5% acetic acid. Neither mu-(morphine and fentanyl) nor delta- ([D-Pen2, D-Pen5]enkephalin- and SNC-80) opioid receptor agonists affected responses to CRD. In contrast, kappa- (U-50,488 and fedotozine) opioid receptor agonists dose-dependently attenuated responses to CRD. Acetic acid sensitized about half of the fibers studied, but neither the potency nor the efficacy of U-50, 488 or FDZ were changed after colonic inflammation. CONCLUSIONS These results suggest a role for peripheral kappa-opioid receptors in the modulation of visceral nociception.", "author" : [ { "dropping-particle" : "", "family" : "Sengupta", "given" : "J N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Su", "given" : "X", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gebhart", "given" : "G F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "1996", "10" ] ] }, "note" : "NULL", "page" : "968-80", "title" : "Kappa, but not mu or delta, opioids attenuate responses to distention of afferent fibers innervating the rat colon.", "type" : "article-journal", "volume" : "111" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISBN" : "0304-3959; 0304-3959", "abstract" : "Preclinical studies suggest that visceral afferents constitutively express kappa-opioid receptors (KORs) and that noxious visceral stimuli can be inhibited at a peripheral site by KOR activation. To test the relevance of these observations to humans, we infused, in a randomized, double blind manner, a peripherally selective KOR agonist (ADL 10-0101) or placebo into six patients with chronic pancreatitis and ongoing abdominal pain despite mu-opioid agonist therapy. Pain was assessed using a pain magnitude estimate, an open ended scale of each patient's choosing and compared to their rating of pain from a 1.6 cm(2) thermode applied to the skin and heated to 49 degrees C for 5s. Normalizing pain scores to this rating as 100, pain prior to study drug treatment was 4070, and was unaffected by placebo infusion in the two individuals receiving this therapy. In contrast, ADL 10-0101 infusion reduced pain score from 63+/-7.6 (mean+/-SE) prior to infusion to 23+/-15 4h after infusion (P{<}0.05 vs. baseline). One patient receiving placebo and one receiving ADL 10-0101 experienced a mild headache during the study. One patient receiving ADL 10-0101 experienced restlessness and another had assymptomatic transient dysrhythmia upon standing after the 4h study. Neither of the treatments affected blood pressure, heart rate, respiratory rate, or oxyhemoglobin saturation, and no patient experienced nausea during the study. These limited data support the hypothesis that human visceral afferents express KOR and that peripherally restricted KOR agonists produce analgesia in patients with chronic visceral pain.", "author" : [ { "dropping-particle" : "", "family" : "Eisenach", "given" : "J C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carpenter", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Curry", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pain", "id" : "ITEM-2", "issue" : "1-2", "issued" : { "date-parts" : [ [ "2003", "1" ] ] }, "note" : "LR: 20071114; GR: M01 RR07122/RR/NCRR NIH HHS/United States; GR: P01 NS41386/NS/NINDS NIH HHS/United States; JID: 7508686; 0 (Analgesics, Opioid); 0 (Receptors, Opioid, kappa); ppublish", "page" : "89-95", "title" : "Analgesia from a peripherally active kappa-opioid receptor agonist in patients with chronic pancreatitis", "type" : "article-journal", "volume" : "101" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1080/00365520601014414", "ISSN" : "0036-5521", "PMID" : "17354119", "abstract" : "OBJECTIVE Animal experiments and clinical observations have indicated a different working profile of oxycodone compared to morphine, and it has previously been shown that oxycodone attenuates visceral pain better than morphine. The objective of this study was to test the effects of oxycodone and morphine on experimental pain in patients with pain caused by chronic pancreatitis. MATERIAL AND METHODS Ten patients took part in this blinded, cross-over study. The analgesic effects of morphine (30 mg, oral), oxycodone (15 mg, oral) and placebo were tested against multimodal (mechanical, thermal and electrical) experimental pain in the skin, muscles and oesophagus. Pain was assessed at baseline and 30, 60 and 90 min after drug administration. RESULTS In the skin and muscles, oxycodone was more effective than placebo and morphine on mechanically (skin: F=12.4, p<0.001, muscle: F=11.0, p<0.001) and thermally (skin: F=8.5, p<0.001) evoked pain. In oesophageal heat pain, the effect of morphine was equal to that of placebo, while oxycodone attenuated pain better than both morphine and placebo (F=9.5, p<0.001). Both morphine and oxycodone were more effective in attenuating mechanical pain in the oesophagus than placebo (F=8.6, p<0.001). After electrical stimulation no differences were seen between the opioids and placebo in any tissue studied. CONCLUSIONS Oxycodone was a stronger analgesic than morphine in several pain modalities in the skin, muscle and oesophagus.", "author" : [ { "dropping-particle" : "", "family" : "Staahl", "given" : "Camilla", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dimcevski", "given" : "Georg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andersen", "given" : "S\u00f8ren Due", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorsgaard", "given" : "Niels", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Christrup", "given" : "Lona L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arendt-Nielsen", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn Mohr", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of gastroenterology", "id" : "ITEM-3", "issue" : "3", "issued" : { "date-parts" : [ [ "2007", "3", "8" ] ] }, "note" : "NULL", "page" : "383-90", "title" : "Differential effect of opioids in patients with chronic pancreatitis: an experimental pain study.", "type" : "article-journal", "volume" : "42" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(110,219,220)", "plainTextFormattedCitation" : "(110,219,220)", "previouslyFormattedCitation" : "(110,219,220)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(110,219,220). Hence, oxycodone may posses an advantage over conventional opioids for pain treatment in CP, but head-to-head comparisons in clinical studies with long-term follow-up are not yet available. Transdermal administration (plaster formulation) of opioids is not recommended as first line opioid therapy for CP, but should be reserved to patients having trouble with tablet ingestion. Hence, in an open label randomized crossover trial, transdermal fentanyl plaster was compared to sustained release morphine tablets. No significant differences were found for pain control or patients’ preference or quality of life, while 44% of patients treated with fentanyl plaster reported side effects mainly as a rash at application site ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0169-4197", "PMID" : "10952406", "abstract" : "BACKGROUND Abdominal pain is the dominant symptom in 50-75% of patients with chronic pancreatitis, often requiring opioid analgesics. Fentanyl, a potent synthetic opioid, can be administered percutaneously at a constant dose and is claimed to have fewer systemic side effects. AIM To evaluate transdermal fentanyl plaster versus sustained release morphine tablets as analgesic treatment of painful chronic pancreatitis. METHODS In an open randomized crossover trial, 18 patients were included. The treatment period was 4 wk for each drug. All patients had immediate-release morphine tablets as rescue medication. RESULTS The dosage of transdermal fentanyl had to be increased on average 50% over that indicated by the manufacturer. When this was done and rescue medication was secured, no difference between the two drugs in primary endpoint or patient preference was observed. There was also no difference in the secondary endpoints, pain control, and quality of life. However, skin side effects, mostly mild, occurred in 44% of the patients during treatment with transdermal fentanyl, and the mean daily dose of immediate release morphine was significantly higher during the transdermal fentanyl period than during the sustained-release morphine period (30.7 mg vs. 14.7 mg [p < 0.01]). CONCLUSION When given in an appropriate dose, transdermal fentanyl might be useful for treatment of some patients with painful chronic pancreatitis, e.g., when tablet ingestion is difficult. However, the dosage often has to be increased above that recommended by the manufacturer. The need of rescue morphine is considerable and skin side effects often occur. Transdermal fentanyl is, therefore, not the ideal first-choice analgesic in patients with painful chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Niemann", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Madsen", "given" : "L G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Larsen", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorsgaard", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International journal of pancreatology : official journal of the International Association of Pancreatology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2000", "6" ] ] }, "note" : "NULL", "page" : "235-40", "title" : "Opioid treatment of painful chronic pancreatitis.", "type" : "article-journal", "volume" : "27" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(221)", "plainTextFormattedCitation" : "(221)", "previouslyFormattedCitation" : "(221)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(221)There is marked inter-individual variability in responsiveness to different opioids, and in circumstances where an individual patient fails to achieve satisfactory pain control and/or they are troubled by unacceptable side effects, a trial of an alternative opioid is indicated. Opioid rotation may be difficult and for guidelines the reader is referred toADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1365-2125.2012.04317.x", "ISSN" : "1365-2125", "PMID" : "22554450", "abstract" : "Clinical studies comparing the response and side effects of various opioids have not been able to show robust differences between drugs. Hence, recommendations of the regulatory authorities have been driven by costs with a general tendency in many countries to restrict physician's use of opioids to morphine. Although this approach is recognized as cost-effective in most cases there is solid evidence that, on an individual patient basis, opioids are not all equal. Therefore it is important to have an armamentarium of strong analgesics in clinical practice to ensure a personalized approach in patients who do not respond to standard treatment. In this review we highlight differences between opioids in human studies from a pharmacological, experimental, clinical and health economics point of view. We provide evidence that individuals respond differently to opioids, and that general differences between classes of opioids exist. We recommend that this recognition is used to individualize treatment in difficult cases allowing physicians to have a wide range of treatment options. In the end this will reduce pain and side effects, leading to improved quality of life for the patient and reduce the exploding pain related costs.", "author" : [ { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jensen", "given" : "Rasmus D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nielsen", "given" : "Lecia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Droney", "given" : "Joanne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Christrup", "given" : "Lona L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arendt-Nielsen", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Riley", "given" : "Julia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dahan", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "British journal of clinical pharmacology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2013", "1" ] ] }, "note" : "From Duplicate 1 (Differences between opioids: pharmacological, experimental, clinical and economical perspectives. - Drewes, Asbj\u00f8rn M; Jensen, Rasmus D; Nielsen, Lecia M; Droney, Joanne; Christrup, Lona L; Arendt-Nielsen, Lars; Riley, Julia; Dahan, Albert)\n\nNULL", "page" : "60-78", "title" : "Differences between opioids: pharmacological, experimental, clinical and economical perspectives.", "type" : "article-journal", "volume" : "75" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(212)", "plainTextFormattedCitation" : "(212)", "previouslyFormattedCitation" : "(212)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(212). In patients with a severe and debilitating pain pattern, a more aggressive top-down approach using opioids combined with adjuvant analgesics as first line therapy may be recommended to control painADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3748/wjg.v19.i42.7292", "ISSN" : "1007-9327", "PMID" : "24259960", "abstract" : "Intense abdominal pain is a prominent feature of chronic pancreatitis and its treatment remains a major clinical challenge. Basic studies of pancreatic nerves and experimental human pain research have provided evidence that pain processing is abnormal in these patients and in many cases resembles that seen in neuropathic and chronic pain disorders. An important ultimate outcome of such aberrant pain processing is that once the disease has advanced and the pathophysiological processes are firmly established, the generation of pain can become self-perpetuating and independent of the initial peripheral nociceptive drive. Consequently, the management of pain by traditional methods based on nociceptive deafferentation (e.g., surgery and visceral nerve blockade) becomes difficult and often ineffective. This novel and improved understanding of pain aetiology requires a paradigm shift in pain management of chronic pancreatitis. Modern mechanism based pain treatments taking into account altered pain processing are likely to increasingly replace invasive therapies targeting the nociceptive source, which should be reserved for special and carefully selected cases. In this review, we offer an overview of the current available pharmacological options for pain management in chronic pancreatitis. In addition, future options for pain management are discussed with special emphasis on personalized pain medicine and multidisciplinarity.", "author" : [ { "dropping-particle" : "", "family" : "Olesen", "given" : "S\u00f8ren S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Juel", "given" : "Jacob", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graversen", "given" : "Carina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kolesnikov", "given" : "Yuri", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "Oliver H G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "World Journal of Gastroenterology", "id" : "ITEM-1", "issue" : "42", "issued" : { "date-parts" : [ [ "2013", "11", "14" ] ] }, "note" : "NULL", "page" : "7292", "title" : "Pharmacological pain management in chronic pancreatitis", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(217)", "plainTextFormattedCitation" : "(217)", "previouslyFormattedCitation" : "(217)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(217).In some patients unconventional treatment with drugs such as ketamine is beneficial. Ketamine, an N-methyl-D-aspartate receptor antagonist, is used not only for anaesthesia, but also as a potent analgesic in acute and chronic pain as well as an antihyperalgesic used to reduce central sensitizationADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1517/14656566.2010.515978", "ISSN" : "1744-7666", "PMID" : "20828267", "abstract" : "IMPORTANCE OF THE FIELD Worldwide the number of patients affected by chronic pain is growing and conventional treatment is often insufficient. Recently the importance of the N-methyl-d-aspartate receptor (NMDAR) in the mechanisms and maintenance of chronic pain was established. Ketamine (introduced in the 1960s as an anesthetic) is the most studied NMDAR antagonist in the treatment of various chronic pain syndromes. AREAS COVERED IN THIS REVIEW The pharmacology, safety and toxicology of ketamine are discussed. Further, electronic databases were scanned for prospective, randomized controlled trials that assessed ketamine's analgesic effect in patients with chronic pain. The focus of this review is on trials published after 2008 that applied long-term intravenous infusions. WHAT THE READER WILL GAIN While most studies on intravenous ketamine show acute analgesic effects, three recent trials on long-term ketamine treatment (days to weeks) demonstrate the effectiveness of ketamine in causing long-term (months) relief of chronic pain. Despite these positive results, further studies are needed on safety/toxicity issues. Other administration modes are less effective in causing long-term pain relief. TAKE HOME MESSAGE There is now evidence form a limited number of studies that pain relief lasting for months is observed after long-term intravenous ketamine infusion, suggesting a modulatory effect of ketamine in the process of chronic pain, possibly via blockade of upregulated NMDAR.", "author" : [ { "dropping-particle" : "", "family" : "Noppers", "given" : "Ingeborg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Niesters", "given" : "Marieke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aarts", "given" : "Leon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Terry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sarton", "given" : "Elise", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dahan", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Expert opinion on pharmacotherapy", "id" : "ITEM-1", "issue" : "14", "issued" : { "date-parts" : [ [ "2010", "10", "9" ] ] }, "note" : "NULL", "page" : "2417-29", "title" : "Ketamine for the treatment of chronic non-cancer pain.", "type" : "article-journal", "volume" : "11" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(222)", "plainTextFormattedCitation" : "(222)", "previouslyFormattedCitation" : "(222)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(222). Multiple studies have consistently produced positive results regarding the use of ketamine in chronic pain patients with central sensitization and hyperalgesia and it thus comprises an interesting remedy to revert reduce central sensitization and its associated hyperalgesia in CP. This was supported by a double-blinded crossover trial designed to evaluate the effect of ketamine infusion on experimental hyperalgesia associated with CPADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/AAP.0b013e3182177022", "ISSN" : "1532-8651", "PMID" : "21490522", "abstract" : "BACKGROUND AND OBJECTIVES Upper abdominal pain is a dominant feature of chronic pancreatitis. A key phenomenon in this context is hyperalgesia, typically associated with N-methyl-d-aspartate receptor activation. This exploratory study evaluates acute effects of S-ketamine, a noncompetitive N-methyl-d-aspartate antagonist, in modulating generalized hyperalgesia in chronic pancreatitis pain. METHODS In a blinded crossover trial, 10 chronic pancreatitis pain patients received S-ketamine for 3 hrs at 2 \u03bcg \u00b7 kg \u00b7 min or placebo infusion at an equivalent rate in randomized order. Clinical pain was assessed via visual analog scale (VAS) and short Dutch Language Version McGill Pain Questionnaire (sf-MPQ-DLV). Pressure pain thresholds (PPTs) were measured in dermatome C5, T4, dorsal T10, L1, and L4, and the sum of PPTs (SOPPT) calculated before, at end of, and after infusion. RESULTS Nine patients completed the study. Median pain VAS before infusion was 29 mm at rest, 32 mm during activity; sf-MPQ-DLV score was 4. For the S-ketamine session median SOPPT change at infusion end was significantly higher than in the placebo session (218; interquartile range [IQR], 116-527, versus -123 [IQR, -330 to 24]; P = 0.005) and significant versus preinfusion values (2109 [IQR, 964-3035] vs 1914 [IQR, 842-2884]; P = 0.03). The SOPPT was unchanged versus preinfusion values and similar between groups at 1 hr after infusion end. No significant changes in VAS and sf-MPQ-DLV occurred. CONCLUSIONS S-ketamine infusion is more effective than placebo in increasing PPTs in chronic pancreatitis pain patients immediately after infusion. This effect did not outlast the infusion. Further research is warranted into S-ketamine use for reducing generalized hyperalgesia and chronic pancreatitis pain.", "author" : [ { "dropping-particle" : "", "family" : "Bouwense", "given" : "Stefan A W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buscher", "given" : "Hessel C J L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goor", "given" : "Harry", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "Oliver H G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Regional anesthesia and pain medicine", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2011", "5" ] ] }, "page" : "303-7", "title" : "S-ketamine modulates hyperalgesia in patients with chronic pancreatitis pain.", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(109)", "plainTextFormattedCitation" : "(109)", "previouslyFormattedCitation" : "(109)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(109). However, there are several limitations with the drug due to the side effects, which may be rather severe with longer-term negative consequences, and a current prospective clinical trial is awaited to establish its role in the management of painful CPADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/bmjopen-2014-007087", "ISSN" : "2044-6055", "PMID" : "25757947", "abstract" : "INTRODUCTION Chronic pancreatitis (CP) is an inflammatory disease that causes irreversible damage to pancreatic tissue. Pain is its most prominent symptom. In the absence of pathology suitable for endoscopic or surgical interventions, pain treatment usually includes opioids. However, opioids often have limited efficacy. Moreover, side effects are common and bothersome. Hence, novel approaches to control pain associated with CP are highly desirable. Sensitisation of the central nervous system is reported to play a key role in pain generation and chronification. Fundamental to the process of central sensitisation is abnormal activation of the N-methyl-D-aspartate receptor, which can be antagonised by S-ketamine. The RESET trial is investigating the analgaesic and antihyperalgesic effect of S-ketamine in patients with CP. METHODS AND ANALYSIS 40 patients with CP will be enrolled. Patients are randomised to receive 8\u2005h of intravenous S-ketamine followed by oral S-ketamine, or matching placebo, for 4\u2005weeks. To improve blinding, 1\u2005mg of midazolam will be added to active and placebo treatment. The primary end point is clinical pain relief as assessed by a daily pain diary. Secondary end points include changes in patient-reported outcome measures, opioid consumption and rates of side effects. The end points are registered through the 4-week medication period and for an additional follow-up period of 8\u2005weeks to investigate long-term effects. In addition, experimental pain measures also serves as secondary end points, and neurophysiological imaging parameters are collected. Furthermore, experimental baseline recordings are compared to recordings from a group of healthy controls to evaluate general aspects of pain processing in CP. ETHICS AND DISSEMINATION The protocol is approved by the North Denmark Region Committee on Health Research Ethics (N-20130040) and the Danish Health and Medicines Authorities (EudraCT number: 2013-003357-17). The results will be disseminated in peer-reviewed journals and at scientific conferences. TRIAL REGISTRATION NUMBER The study is registered at (EudraCT number 2013-003357-17).", "author" : [ { "dropping-particle" : "", "family" : "Juel", "given" : "Jacob", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olesen", "given" : "S\u00f8ren Schou", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olesen", "given" : "Anne Estrup", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Poulsen", "given" : "Jakob Lykke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dahan", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "Oliver", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Madzak", "given" : "Adnan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fr\u00f8kj\u00e6r", "given" : "Jens Br\u00f8ndum", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn Mohr", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMJ open", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2015", "3", "10" ] ] }, "note" : "NULL", "page" : "e007087", "title" : "Study protocol for a randomised, double-blinded, placebo-controlled, clinical trial of S-ketamine for pain treatment in patients with chronic pancreatitis (RESET trial).", "type" : "article-journal", "volume" : "5" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(223)", "plainTextFormattedCitation" : "(223)", "previouslyFormattedCitation" : "(223)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(223).Experimental and clinical evidence suggest a key role for nerve growth factor (NGF) in the generation and maintenance of a wide range of pain states. Consequently, drug discovery efforts have resulted in several humanized anti-NGF monoclonal antibodies that have entered clinical trials as potential analgesicsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/cpt.20", "ISSN" : "1532-6535", "PMID" : "25670514", "abstract" : "Existing analgesics fail to provide adequate pain relief in a significant proportion of patients complaining of chronic pain. Furthermore, their use is limited by tolerability and safety concerns. Thus, there is a huge unmet need for effective and safe innovative painkillers. Considering the major role of nerve growth factor (NGF) in the generation and maintenance of a wide range of pain states, the issue is whether anti-NGF biologics under development might offer such an opportunity.", "author" : [ { "dropping-particle" : "", "family" : "Bannwarth", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kostine", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical pharmacology and therapeutics", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2015", "2" ] ] }, "note" : "NULL", "page" : "122-4", "title" : "Biologics in the treatment of chronic pain: a new era of therapy?", "type" : "article-journal", "volume" : "97" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(224)", "plainTextFormattedCitation" : "(224)", "previouslyFormattedCitation" : "(224)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(224). NGF is up-regulated in patients with CP and is known to play a pivotal role in the process of peripheral sensitization. Therefore NGF-antagonism may also be effective for pain relief in these patients and in other visceral pain syndromes where up-regulation of NGF is assumed to mediate painADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1053/j.gastro.2011.03.046", "ISSN" : "1528-0012", "PMID" : "21473865", "abstract" : "BACKGROUND & AIMS The pathogenesis of pain in chronic pancreatitis (CP) is poorly understood and treatment remains difficult. We hypothesized that nerve growth factor (NGF) plays a key role in this process via its effects on the transient receptor potential vanilloid 1, TRPV1. METHODS CP was induced by intraductal injection of trinitrobenzene sulfonic acid in rats. After 3 weeks, anti-NGF antibody or control serum was administered daily for 1 week. Pancreatic hyperalgesia was assessed by nocifensive behavioral response to electrical stimulation of the pancreas as well as by referred somatic pain assessed by von Frey filament testing. TRPV1 currents in pancreatic sensory neurons were examined by patch-clamp. The expression and function of TRPV1 in pancreas-specific nociceptors was examined by immunostaining and quantification of messenger RNA levels. RESULTS Blockade of NGF significantly attenuated pancreatic hyperalgesia and referred somatic pain compared with controls. It also decreased TRPV1 current density and open probability and reduced the proportion of pancreatic sensory neurons that expressed TRPV1 as well as levels of TRPV1 in these neurons. CONCLUSIONS These findings emphasize a key role for NGF in pancreatic pain and highlight the role it plays in the modulation of TRPV1 expression and activity in CP.", "author" : [ { "dropping-particle" : "", "family" : "Zhu", "given" : "Yaohui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Colak", "given" : "Tugba", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shenoy", "given" : "Mohan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Liansheng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pai", "given" : "Reetesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Cuiping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mehta", "given" : "Kshama", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pasricha", "given" : "Pankaj Jay", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2011", "7" ] ] }, "note" : "NULL", "page" : "370-7", "title" : "Nerve growth factor modulates TRPV1 expression and function and mediates pain in chronic pancreatitis.", "type" : "article-journal", "volume" : "141" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(225)", "plainTextFormattedCitation" : "(225)", "previouslyFormattedCitation" : "(225)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(225).Somastotatin-analogue inhibits pancreatic secretion by blocking CCK and secretin release and also by a direct inhibitory effect on acinar cells. These effects may theoretically alleviate pain through reduction of pancreatic ductal pressure and by lowering the central effects of CCK. There are conflicting data about the efficacy of somastotatin-analogues for pain in CP. While early pilot series of octreotide showed an effect on pain control, this effect could not be confirmed in later randomized controlled trialsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0017-5749", "PMID" : "7698708", "abstract" : "It has been suggested that pancreatic ductal hypertension, secondary to pancreatic outflow obstruction, is a cause of pain in chronic pancreatitis. This study investigated the effect of inhibiting pancreatic secretion with octreotide in chronic pancreatitis pain. Ten patients with chronic alcoholic pancreatitis and severe daily pain were included in an intraindividual double blind crossover study. All patients received octreotide (3 x 100 micrograms/day subcutaneously) and placebo (3 x 0.9% saline solution subcutaneously) for three days at random. Between both treatment phases a two day washout period was interposed. Intensity of pain (visual analogue scale) and analgesic consumption were carefully registered. Pancreatic secretion was monitored daily by measuring faecal chymotrypsin concentration. It was found that during the administration of octreotide, pancreatic secretion was strongly inhibited (faecal chymotrypsin mean (SD) 1.7 (0.6) U/g) with respect to placebo (9.6 (4.2) U/g) and washout (7.6 (3.1) U/g) periods (p < 0.001). Pain score (29.6 (4.5) v 28.7 (5.8)) and consumption of analgesics were no different during the octreotide and placebo periods. It is concluded that short term inhibition of pancreatic secretion does not result in pain relief in patients with chronic pancreatitis. This finding is in contrast with the hypothesis that outflow obstruction of pancreatic secretion with consequent ductal hypertension is an important cause of severe persistent pain in chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Malfertheiner", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mayer", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "B\u00fcchler", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dom\u00ednguez-Mu\u00f1oz", "given" : "J E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schiefer", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ditschuneit", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gut", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "1995", "3" ] ] }, "note" : "NULL", "page" : "450-4", "title" : "Treatment of pain in chronic pancreatitis by inhibition of pancreatic secretion with octreotide.", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(226)", "plainTextFormattedCitation" : "(226)", "previouslyFormattedCitation" : "(226)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(226). Other drugs such as for example clonidine (centrally acting α2 adrenergic agonist), quetiepine (second generation antipsychotic) and neurokinin-1 receptor (NK-1R) antagonists have all demonstrated analgesic efficacy and may be used in selected patientsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1170-229X", "PMID" : "11302287", "abstract" : "Irritable bowel syndrome (IBS) is a functional gut disorder the diagnosis of which is based on clinical symptoms as set forth by the Rome criteria. As the population ages, especially with the population of patients >75 years of age expanding greatly over the next 10 years, IBS is becoming one of the most common diseases of the elderly. Thus far, developing treatment strategies for patients with IBS has been difficult because of the lack of pharmacological targets and the wide range of symptomatology. Additionally, demonstration of a therapeutic benefit is difficult in the presence of a high placebo response observed regardless of the therapy employed. Fibre, antidiarrhoeals and antispasmodics all play some role in the symptomatic treatment of IBS. With the evolution of IBS as a disorder of visceral hypersensitivity, new drugs have been developed that target the enteric nervous system. Tricyclic antidepressants (TCAs) have been found to target the enteric neurons and play a role in pain modulation. Currently, the TCAs are recommended only for severe cases of IBS pain. The newest class of drugs to be approved for use in IBS are the serotonin (5-hydroxytryptamine; 5-HT) antagonists. Specifically, the 5-HT3 receptor antagonists have been shown to decrease symptoms in female patients with IBS. A related class of drugs, the 5-HT4 receptor agonists, is being developed for the treatment of constipation-predominant IBS. Further investigation into the role of spinal afferent neurons in visceral hypersensitivity is at the forefront of IBS research. Several experimental drug therapies for IBS are also discussed in this review including N-methyl-D-aspartate receptor antagonists, neurokinin-1 receptor antagonists, octreotide, clonidine and the selective M3 receptor antagonist, zamifenacin.", "author" : [ { "dropping-particle" : "", "family" : "Dunphy", "given" : "R C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Verne", "given" : "G N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Drugs & aging", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2001" ] ] }, "note" : "NULL", "page" : "201-11", "title" : "Drug treatment options for irritable bowel syndrome: managing for success.", "type" : "article-journal", "volume" : "18" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(227)", "plainTextFormattedCitation" : "(227)", "previouslyFormattedCitation" : "(227)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(227). It may also be indicated to use benzodiazepines, anti-psychotics or cannabinoids in difficult cases although it should be stressed that no data in CP are not yet available to document their use. 34290073660003847-1206760Figure 2: Suggested algorithm for pharmacological treatment (grey boxes) of pain in chronic pancreatitis. “Autonomic” pain is defined as a primary pain type that is not related to local complications such as pseudocysts or obvious duct strictures and stones. In most cases, combination therapies are necessary. Treatment with antidepressives is guided by psychological evaluation including assessment of catastrophizing, depression etc. In case gabapentinoids are considered we use evaluation of the ration between segmental and generalised hyperalgesia (see text). Of note, treatment with gabapentinoids, TCA, SNRI (or SSRI in selected cases) should be titrated slowly until sufficient effect or intolerable adverse effects occur. Treatment shall be individualised due to major differences in receptor properties and analgesic mechanisms between patients. NSAIDs are normally not indicated and should be used carefully. Opioids shall be avoided if possible due to the major side effects on the gastrointestinal tract etc., but in severe pain they may be prescribed for limited periods and the physician shall always be aware of opioid induced bowel dysfunction and hyperalgesia (narcotic bowel). The timing of surgery is up to discussion (please see Q11) and is placed in the bottom of this algorithm mainly dealing with medical therapy.“Plus sign” indicate sufficient/satisfactory effect. “Minus sign” indicate insufficient effectESWL: extracorporal shock wave lithotrypsyPCM: paracetamolNSAID: non-steroidal anti-inflammatory drugs TCA: tricyclic antidepressivesSNRI: serotonin-noradrenalin reuptake inhibitorsSSRI: selective serotonin reuptake inhibitorsOIBD: opioid induced bowel dysfunction00Figure 2: Suggested algorithm for pharmacological treatment (grey boxes) of pain in chronic pancreatitis. “Autonomic” pain is defined as a primary pain type that is not related to local complications such as pseudocysts or obvious duct strictures and stones. In most cases, combination therapies are necessary. Treatment with antidepressives is guided by psychological evaluation including assessment of catastrophizing, depression etc. In case gabapentinoids are considered we use evaluation of the ration between segmental and generalised hyperalgesia (see text). Of note, treatment with gabapentinoids, TCA, SNRI (or SSRI in selected cases) should be titrated slowly until sufficient effect or intolerable adverse effects occur. Treatment shall be individualised due to major differences in receptor properties and analgesic mechanisms between patients. NSAIDs are normally not indicated and should be used carefully. Opioids shall be avoided if possible due to the major side effects on the gastrointestinal tract etc., but in severe pain they may be prescribed for limited periods and the physician shall always be aware of opioid induced bowel dysfunction and hyperalgesia (narcotic bowel). The timing of surgery is up to discussion (please see Q11) and is placed in the bottom of this algorithm mainly dealing with medical therapy.“Plus sign” indicate sufficient/satisfactory effect. “Minus sign” indicate insufficient effectESWL: extracorporal shock wave lithotrypsyPCM: paracetamolNSAID: non-steroidal anti-inflammatory drugs TCA: tricyclic antidepressivesSNRI: serotonin-noradrenalin reuptake inhibitorsSSRI: selective serotonin reuptake inhibitorsOIBD: opioid induced bowel dysfunctionIn practice pain treatment is mainly guided by evidence from somatic pain studies together with individual experience and traditions. However, the variability in phenotypic presentation of different pain syndromes is found to be greater between patients than between different pain syndromes, indicating that mechanistic etiologies are based on the individual rather than the level of disease ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.pain.2008.01.006", "ISSN" : "0304-3959", "PMID" : "18289791", "abstract" : "Neuropathic pain can be caused by a variety of nerve lesions and it is unsettled whether it should be categorised into distinct clinical subtypes depending on aetiology or type of nerve lesion or individualised as a specific group, based on common symptomatology across aetiologies. In this study, we used a multivariate statistical method (multiple correspondence analyses) to investigate associations between neuropathic positive symptoms (assessed with a specific questionnaire, the Neuropathic Pain Symptom Inventory [NPSI]) and aetiologies, types of nerve lesion and pain localisations. We also examined the internal structure of the NPSI and its relevance to evaluation of symptoms of evoked pains by exploring their relationships with clinician-based quantified measures of allodynia and hyperalgesia. This study included 482 consecutive patients (53% men; mean age: 58+/-15 years) with pain associated with peripheral or central lesions. Factor analysis showed that neuropathic symptoms of the NPSI can be categorised into five dimensions. Spearman correlation coefficients indicated that self-reported pain evoked by brush, pressure and cold stimuli strongly correlated to allodynia/hyperalgesia to brush, von Frey hairs and cold stimuli (p<0.0001, n=90). Multiple correspondence analyses indicated few associations between symptoms (or dimensions) and aetiologies, types of lesions, or pain localisations. Exceptions included idiopathic trigeminal neuralgia and postherpetic neuralgia. We found that there are more similarities than differences in the neuropathic positive symptoms associated with a large variety of peripheral and central lesions, providing rationale for subgrouping aetiologically diverse neuropathic patients into a specific multidimensional category for therapeutic management.", "author" : [ { "dropping-particle" : "", "family" : "Attal", "given" : "N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fermanian", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fermanian", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lanteri-Minet", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alchaar", "given" : "H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bouhassira", "given" : "D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pain", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2008", "8", "31" ] ] }, "page" : "343-353", "title" : "Neuropathic pain: Are there distinct subtypes depending on the aetiology or anatomical lesion?", "type" : "article-journal", "volume" : "138" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(228)", "plainTextFormattedCitation" : "(228)", "previouslyFormattedCitation" : "(228)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(228). In figure 2 an example of a treatment algorithm used at Centre for Pancreatic Diseases, Aalborg University Hospital, Denmark is shown. A multidisciplinary approach is suggested both for evaluation and treatment of patients. This includes neurophysiological and psychological testing whereby specific pain mechanisms and psychiatric comorbidity are detected and rational treatment can be initiated. For example segmental hyperalgesia of the epigastric skin area (pancreatic viscerotome), detected by quantitative sensory testing, may serve as a clinical marker of central sensitization and predict the response to gabapentinoidsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0057963", "ISSN" : "1932-6203", "PMID" : "23469256", "abstract" : "BACKGROUND A major problem in pain medicine is the lack of knowledge about which treatment suits a specific patient. We tested the ability of quantitative sensory testing to predict the analgesic effect of pregabalin and placebo in patients with chronic pancreatitis. METHODS Sixty-four patients with painful chronic pancreatitis received pregabalin (150-300 mg BID) or matching placebo for three consecutive weeks. Analgesic effect was documented in a pain diary based on a visual analogue scale. Responders were defined as patients with a reduction in clinical pain score of 30% or more after three weeks of study treatment compared to baseline recordings. Prior to study medication, pain thresholds to electric skin and pressure stimulation were measured in dermatomes T10 (pancreatic area) and C5 (control area). To eliminate inter-subject differences in absolute pain thresholds an index of sensitivity between stimulation areas was determined (ratio of pain detection thresholds in pancreatic versus control area, ePDT ratio). Pain modulation was recorded by a conditioned pain modulation paradigm. A support vector machine was used to screen sensory parameters for their predictive power of pregabalin efficacy. RESULTS The pregabalin responders group was hypersensitive to electric tetanic stimulation of the pancreatic area (ePDT ratio 1.2 (0.9-1.3)) compared to non-responders group (ePDT ratio: 1.6 (1.5-2.0)) (P\u200a=\u200a0.001). The electrical pain detection ratio was predictive for pregabalin effect with a classification accuracy of 83.9% (P\u200a=\u200a0.007). The corresponding sensitivity was 87.5% and specificity was 80.0%. No other parameters were predictive of pregabalin or placebo efficacy. CONCLUSIONS The present study provides first evidence that quantitative sensory testing predicts the analgesic effect of pregabalin in patients with painful chronic pancreatitis. The method can be used to tailor pain medication based on patient's individual sensory profile and thus comprises a significant step towards personalized pain medicine.", "author" : [ { "dropping-particle" : "", "family" : "Olesen", "given" : "S\u00f8ren S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graversen", "given" : "Carina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bouwense", "given" : "Stefan A W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goor", "given" : "Harry", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "Oliver H G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "editor" : [ { "dropping-particle" : "", "family" : "Miaskowski", "given" : "Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2013", "3", "1" ] ] }, "note" : "NULL", "page" : "e57963", "title" : "Quantitative sensory testing predicts pregabalin efficacy in painful chronic pancreatitis.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(107)", "plainTextFormattedCitation" : "(107)", "previouslyFormattedCitation" : "(107)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(107). The tests are partly described in Q3 where more references can be found. Also, up to 40% of chronic pain patients are depressed and identification of mood disorders may identify patients where adjuvant therapy with antidepressants are particular beneficial (see section about psychological treatment). In addition, it is of outmost importance to identify secondary causes for pain (e.g. peptic ulcers or pseudocysts) as these are often easy to diagnose and treat, and secondary causes of pain should always be considered when the patient is experiencing an exacerbation in pain symptoms. The multidisciplinary approach to pain in CP, although typically used in centers dedicated for pancreatic pain therapy, may also be used in less specialized settings to guide pharmacotherapy in difficult cases. Over the past few decades, significant progress has been made in our understanding of the basic science of pain and the effect of analgesics. Non-invasive human methods using methods such as quantitative sensory testing, immunohistochemistry, neurophysiological evaluation, and assessment of brain function with electrophysiological methods and imaging have provided greater insights into the mechanisms of pain in CP and may lead to the development of more specific and effective therapies that may be individualized to fit the characteristics of the individual patientADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3748/wjg.v19.i42.7292", "ISSN" : "1007-9327", "PMID" : "24259960", "abstract" : "Intense abdominal pain is a prominent feature of chronic pancreatitis and its treatment remains a major clinical challenge. Basic studies of pancreatic nerves and experimental human pain research have provided evidence that pain processing is abnormal in these patients and in many cases resembles that seen in neuropathic and chronic pain disorders. An important ultimate outcome of such aberrant pain processing is that once the disease has advanced and the pathophysiological processes are firmly established, the generation of pain can become self-perpetuating and independent of the initial peripheral nociceptive drive. Consequently, the management of pain by traditional methods based on nociceptive deafferentation (e.g., surgery and visceral nerve blockade) becomes difficult and often ineffective. This novel and improved understanding of pain aetiology requires a paradigm shift in pain management of chronic pancreatitis. Modern mechanism based pain treatments taking into account altered pain processing are likely to increasingly replace invasive therapies targeting the nociceptive source, which should be reserved for special and carefully selected cases. In this review, we offer an overview of the current available pharmacological options for pain management in chronic pancreatitis. In addition, future options for pain management are discussed with special emphasis on personalized pain medicine and multidisciplinarity.", "author" : [ { "dropping-particle" : "", "family" : "Olesen", "given" : "S\u00f8ren S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Juel", "given" : "Jacob", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graversen", "given" : "Carina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kolesnikov", "given" : "Yuri", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "Oliver H G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "World Journal of Gastroenterology", "id" : "ITEM-1", "issue" : "42", "issued" : { "date-parts" : [ [ "2013", "11", "14" ] ] }, "note" : "NULL", "page" : "7292", "title" : "Pharmacological pain management in chronic pancreatitis", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/j.1532-2149.2013.00330.x", "ISSN" : "1532-2149", "PMID" : "23658120", "abstract" : "The role of quantitative sensory testing (QST) in prediction of analgesic effect in humans is scarcely investigated. This updated review assesses the effectiveness in predicting analgesic effects in healthy volunteers, surgical patients and patients with chronic pain. A systematic review of English written, peer-reviewed articles was conducted using PubMed and Embase (1980-2013). Additional studies were identified by chain searching. Search terms included 'quantitative sensory testing', 'sensory testing' and 'analgesics'. Studies on the relationship between QST and response to analgesic treatment in human adults were included. Appraisal of the methodological quality of the included studies was based on evaluative criteria for prognostic studies. Fourteen studies (including 720 individuals) met the inclusion criteria. Significant correlations were observed between responses to analgesics and several QST parameters including (1) heat pain threshold in experimental human pain, (2) electrical and heat pain thresholds, pressure pain tolerance and suprathreshold heat pain in surgical patients, and (3) electrical and heat pain threshold and conditioned pain modulation in patients with chronic pain. Heterogeneity among studies was observed especially with regard to application of QST and type and use of analgesics. Although promising, the current evidence is not sufficiently robust to recommend the use of any specific QST parameter in predicting analgesic response. Future studies should focus on a range of different experimental pain modalities rather than a single static pain stimulation paradigm.", "author" : [ { "dropping-particle" : "", "family" : "Grosen", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fischer", "given" : "I W D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olesen", "given" : "A E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "A M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European journal of pain (London, England)", "id" : "ITEM-2", "issue" : "9", "issued" : { "date-parts" : [ [ "2013", "10" ] ] }, "note" : "NULL", "page" : "1267-80", "title" : "Can quantitative sensory testing predict responses to analgesic treatment?", "type" : "article-journal", "volume" : "17" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(217,229)", "plainTextFormattedCitation" : "(217,229)", "previouslyFormattedCitation" : "(217,229)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(217,229). Until then we are left with the guidelines outlined above. However, treatment should always be individualized and preferably initiated and monitored by expert pancreatologists due to the complexity of pain and complications to CP that always needs to be considered and treated appropriately.Myriam Delhaye, Shuiji Isaji and Stefan A W BouwenseQ7. Is endoscopical therapy effective for pain treatment in CP?The best candidates for successful treatment of painful CP with first-line endoscopical therapy are middle-aged patients with distal obstruction of the main pancreatic duct (single stone and/or single stricture in the head of the pancreas) and in the early stage of the disease, that means as soon as possible after the first pain attack. Endoscopical therapy can be combined with Extracorporeal Shock Wave Lithotripsy (ESWL) in the presence of large (> 4 mm) obstructive stone(s) located in the pancreatic head, and with ductal stenting in the presence of a single main pancreatic duct stricture that induces a markedly dilated duct. (Quality assessment: moderate; Recommendation: strong; Agreement: conditional)Endoscopical therapy (ET) in painful chronic pancreatitis (CP) is based on the rationale that pain is related to an outflow obstruction of the main pancreatic duct (MPD) due to stricture(s) or pancreatic intraductal stone(s).Therefore ET is indicated for selected patients with both:persistent (continuous or recurrent) pain related to CP after failed conservative pain management;outflow obstruction of the MPD (i.e. MPD dilatation 5 mm), secondary to ductal stricture(s) and/or stone(s) amenable to ET.Retrospective/observational studies: According to a multicenter study of > 1,000 patients who had been selected for ET of painful CP, MPD obstruction was caused by pancreatic stone(s) alone, ductal stricture(s) alone and a combination of stone(s) and stricture(s) in 18%, 47%, and 32% of cases respectivelyADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1055/s-2002-34256", "ISSN" : "0013-726X", "PMID" : "12244496", "abstract" : "BACKGROUND AND STUDY AIMS Endoscopic ductal decompression therapy has become an established method of treating patients with painful obstructive chronic pancreatitis. Smaller series, mostly with a medium-term follow-up period, have reported encouraging results. The present analysis presents long-term follow-up data from a large multicenter patient cohort. PATIENTS AND METHODS Patients with painful chronic pancreatitis and with ductal obstruction due to either strictures and/or stones treated endoscopically at eight different centers underwent follow-up after 2 - 12 years (mean 4.9 years). The patients' clinical data, the rate of technical success, and complications were recorded from the charts. Follow-up data were prospectively obtained using structured questionnaires; the main parameter for evaluating treatment success was a significant reduction in pain (no pain or only weak pain). RESULTS Follow-up data were obtained from 1018 of 1211 patients treated (84%) with mainly strictures (47%), stones (18%), or strictures plus stones (32%). At the long-term follow-up, 60% of the patients had their endotherapy completed, 16% were still receiving some form of endoscopic treatment, and 24% had undergone surgery. The long-term success of endotherapy was 86% in the entire group, but only 65% in an intention-to-treat analysis. There were no significant differences between the patient groups with regard to either strictures, stones, or both. Pancreatic function was not positively affected by endoscopic therapy. CONCLUSIONS Endoscopic ductal decompression therapy offers relief of pain in two-thirds of the patients when it is used as the only form of treatment. One-quarter of the patients have to undergo surgery.", "author" : [ { "dropping-particle" : "", "family" : "R\u00f6sch", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Daniel", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scholz", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huibregtse", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smits", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schneider", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ell", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haber", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Riemann", "given" : "J-F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jakobs", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hintze", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adler", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Neuhaus", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zavoral", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zavada", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schusdziarra", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Soehendra", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "European Society of Gastrointestinal Endoscopy Research Group", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Endoscopy", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2002", "10" ] ] }, "note" : "NULL", "page" : "765-71", "title" : "Endoscopic treatment of chronic pancreatitis: a multicenter study of 1000 patients with long-term follow-up.", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(230)", "plainTextFormattedCitation" : "(230)", "previouslyFormattedCitation" : "(230)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(230).ERCP can achieve MPD drainage by pancreatic sphincterotomy of the major and/or minor papilla, by temporarily stent insertion in the case of dominant stricture in the head of the pancreas, or by pancreatic stone extraction, usually after fragmentation with ESWL. The effectiveness of ET is usually the result of these combined procedures, all of these aimed to restore drainage of the MPD. With this approach 79% - 85% of patients experienced complete or partial pain relief in the short-term (follow-up (FU) < 2 years) (Tables 1 and 1S, all Tables appear after Q8), 76% - 94% in the medium-term (FU 2 – 5 years) (Tables 2 and 2S) and 66% - 96% in the long-term (FU > 5 years) (Tables 3 and 3S). Endoscopic MPD drainage yielded similar results in the different categories of patients (stone(s) alone, ductal stricture(s) alone and both stone(s) and stricture(s)), with 51% (523 / 1018) of patients having no pain at all at a mean FU of 4.9 years (intention-to-treat analysis)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1055/s-2002-34256", "ISSN" : "0013-726X", "PMID" : "12244496", "abstract" : "BACKGROUND AND STUDY AIMS Endoscopic ductal decompression therapy has become an established method of treating patients with painful obstructive chronic pancreatitis. Smaller series, mostly with a medium-term follow-up period, have reported encouraging results. The present analysis presents long-term follow-up data from a large multicenter patient cohort. PATIENTS AND METHODS Patients with painful chronic pancreatitis and with ductal obstruction due to either strictures and/or stones treated endoscopically at eight different centers underwent follow-up after 2 - 12 years (mean 4.9 years). The patients' clinical data, the rate of technical success, and complications were recorded from the charts. Follow-up data were prospectively obtained using structured questionnaires; the main parameter for evaluating treatment success was a significant reduction in pain (no pain or only weak pain). RESULTS Follow-up data were obtained from 1018 of 1211 patients treated (84%) with mainly strictures (47%), stones (18%), or strictures plus stones (32%). At the long-term follow-up, 60% of the patients had their endotherapy completed, 16% were still receiving some form of endoscopic treatment, and 24% had undergone surgery. The long-term success of endotherapy was 86% in the entire group, but only 65% in an intention-to-treat analysis. There were no significant differences between the patient groups with regard to either strictures, stones, or both. Pancreatic function was not positively affected by endoscopic therapy. CONCLUSIONS Endoscopic ductal decompression therapy offers relief of pain in two-thirds of the patients when it is used as the only form of treatment. One-quarter of the patients have to undergo surgery.", "author" : [ { "dropping-particle" : "", "family" : "R\u00f6sch", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Daniel", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scholz", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huibregtse", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smits", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schneider", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ell", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haber", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Riemann", "given" : "J-F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jakobs", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hintze", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adler", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Neuhaus", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zavoral", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zavada", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schusdziarra", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Soehendra", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "European Society of Gastrointestinal Endoscopy Research Group", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Endoscopy", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2002", "10" ] ] }, "note" : "NULL", "page" : "765-71", "title" : "Endoscopic treatment of chronic pancreatitis: a multicenter study of 1000 patients with long-term follow-up.", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(230)", "plainTextFormattedCitation" : "(230)", "previouslyFormattedCitation" : "(230)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(230).Several independent series from different parts of the world have reported the long-term outcome (FU 24 months) after endoscopic therapy ( ESWL for 60% of patients) in a total of 1657 patients (Tables 4 and 4s). Complete or partial pain relief was reported on an average in 78% (43% - 85%) of patients and surgery was avoided in 80% (74% - 96%) of patients (1265 / 1580) in studies where this data was available (Tables 4 and 4S).These studies are relatively homogeneous regarding baseline characteristics of included patients (mostly middle-aged men with pain, recurrent or continuous, alcohol abuse as main etiology of CP, average duration of disease prior to ET around 3 – 5 years, severe CP with endocrine / exocrine insufficiency at baseline around 30%) (Tables 1 to 4).However, the quality of evidence of reported results remains low in most of these retrospective observational non-randomized studies, with heterogeneity mainly in the use of unstandardized pain relief assessment, in the duration of follow-up and in the sample size, with no comparative analysis with a control group. Moreover, the retrospective design of a study may overestimate the treatment success rate.Randomized studies: Only two randomized controlled trial (RCT) were included in two Cochrane reviews published in 2012 and 2015ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1469-493X", "author" : [ { "dropping-particle" : "", "family" : "Ahmed Ali", "given" : "Usama", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pahlplatz", "given" : "Johanna M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nealon", "given" : "Wiliam H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goor", "given" : "Harry", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gooszen", "given" : "Hein G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boermeester", "given" : "Marja A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cochrane Database of Systematic Reviews", "editor" : [ { "dropping-particle" : "", "family" : "Ahmed Ali", "given" : "Usama", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "0" ] ] }, "page" : "CD007884", "publisher" : "John Wiley & Sons, Ltd", "publisher-place" : "Chichester, UK", "title" : "Endoscopic or surgical intervention for painful obstructive chronic pancreatitis", "type" : "chapter", "volume" : "1" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(231)", "plainTextFormattedCitation" : "(231)", "previouslyFormattedCitation" : "(231)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(231) comparing ET and surgery. They included in the ET arm, only 19 patients for the highest quality RCTADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1056/NEJMoa060610", "ISSN" : "0028-4793", "PMID" : "17301298", "abstract" : "BACKGROUND For patients with chronic pancreatitis and a dilated pancreatic duct, ductal decompression is recommended. We conducted a randomized trial to compare endoscopic and surgical drainage of the pancreatic duct. METHODS All symptomatic patients with chronic pancreatitis and a distal obstruction of the pancreatic duct but without an inflammatory mass were eligible for the study. We randomly assigned patients to undergo endoscopic transampullary drainage of the pancreatic duct or operative pancreaticojejunostomy. The primary end point was the average Izbicki pain score during 2 years of follow-up. The secondary end points were pain relief at the end of follow-up, physical and mental health, morbidity, mortality, length of hospital stay, number of procedures undergone, and changes in pancreatic function. RESULTS Thirty-nine patients underwent randomization: 19 to endoscopic treatment (16 of whom underwent lithotripsy) and 20 to operative pancreaticojejunostomy. During the 24 months of follow-up, patients who underwent surgery, as compared with those who were treated endoscopically, had lower Izbicki pain scores (25 vs. 51, P<0.001) and better physical health summary scores on the Medical Outcomes Study 36-Item Short-Form General Health Survey questionnaire (P=0.003). At the end of follow-up, complete or partial pain relief was achieved in 32% of patients assigned to endoscopic drainage as compared with 75% of patients assigned to surgical drainage (P=0.007). Rates of complications, length of hospital stay, and changes in pancreatic function were similar in the two treatment groups, but patients receiving endoscopic treatment required more procedures than did patients in the surgery group (a median of eight vs. three, P<0.001). CONCLUSIONS Surgical drainage of the pancreatic duct was more effective than endoscopic treatment in patients with obstruction of the pancreatic duct due to chronic pancreatitis. (Current Controlled Trials number, ISRCTN04572410 [controlled-].).", "author" : [ { "dropping-particle" : "", "family" : "Cahen", "given" : "Djuna L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gouma", "given" : "Dirk J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nio", "given" : "Yung", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rauws", "given" : "Erik A. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boermeester", "given" : "Marja A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Busch", "given" : "Olivier R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stoker", "given" : "Jaap", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lam\u00e9ris", "given" : "Johan S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dijkgraaf", "given" : "Marcel G.W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huibregtse", "given" : "Kees", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruno", "given" : "Marco J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "New England Journal of Medicine", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2007", "2", "15" ] ] }, "page" : "676-684", "title" : "Endoscopic versus Surgical Drainage of the Pancreatic Duct in Chronic Pancreatitis", "type" : "article-journal", "volume" : "356" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(232)", "plainTextFormattedCitation" : "(232)", "previouslyFormattedCitation" : "(232)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(232) and 36 patients in the other oneADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1055/s-2003-40237", "ISSN" : "0013-726X", "PMID" : "12822088", "abstract" : "BACKGROUND AND STUDY AIMS Invasive treatment for abdominal pain due to chronic pancreatitis may be either surgical or endoscopic, particularly in cases of ductal obstruction. To date, the data published on the effectiveness of these two forms of therapy have been mostly retrospective, and there have been no randomized studies. A prospective, randomized study comparing surgery with endoscopy in patients with painful obstructive chronic pancreatitis was therefore conducted. PATIENTS AND METHODS Consecutive patients with pancreatic duct obstruction and pain were invited to participate in a randomized trial comparing endotherapy and surgery, the latter consisting of resection and drainage procedures, depending on the patient's individual situation. Patients who did not agree to participation and randomization were also further assessed using the same follow-up protocol. RESULTS Of 140 eligible patients, only 72 agreed to be randomized. Surgery consisted of resection (80 %) and drainage (20 %) procedures, while endotherapy included sphincterotomy and stenting (52 %) and/or stone removal (23 %). In the entire group, the initial success rates were similar for both groups, but at the 5-year follow-up, complete absence of pain was more frequent after surgery (37 % vs. 14 %), with the rate of partial relief being similar (49 % vs. 51 %). In the randomized subgroup, results were similar (pain absence 34 % after surgery vs. 15 % after endotherapy, relief 52 % after surgery vs. 46 % after endotherapy). The increase in body weight was also greater by 20 - 25 % in the surgical group, while new-onset diabetes developed with similar frequency in both groups (34 - 43 %), again with no differences between the results for the whole group and the randomized subgroup. CONCLUSIONS Surgery is superior to endotherapy for long-term pain reduction in patients with painful obstructive chronic pancreatitis. Better selection of patients for endotherapy may be helpful in order to maximize results. Due to its low degree of invasiveness, however, endotherapy can be offered as a first-line treatment, with surgery being performed in case of failure and/or recurrence.", "author" : [ { "dropping-particle" : "", "family" : "D\u00edte", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruzicka", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zboril", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Novotn\u00fd", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Endoscopy", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2003", "7" ] ] }, "note" : "NULL", "page" : "553-558", "title" : "A Prospective, Randomized Trial Comparing Endoscopic and Surgical Therapy for Chronic Pancreatitis", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(233)", "plainTextFormattedCitation" : "(233)", "previouslyFormattedCitation" : "(233)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(233).In the first RCTADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1056/NEJMoa060610", "ISSN" : "0028-4793", "PMID" : "17301298", "abstract" : "BACKGROUND For patients with chronic pancreatitis and a dilated pancreatic duct, ductal decompression is recommended. We conducted a randomized trial to compare endoscopic and surgical drainage of the pancreatic duct. METHODS All symptomatic patients with chronic pancreatitis and a distal obstruction of the pancreatic duct but without an inflammatory mass were eligible for the study. We randomly assigned patients to undergo endoscopic transampullary drainage of the pancreatic duct or operative pancreaticojejunostomy. The primary end point was the average Izbicki pain score during 2 years of follow-up. The secondary end points were pain relief at the end of follow-up, physical and mental health, morbidity, mortality, length of hospital stay, number of procedures undergone, and changes in pancreatic function. RESULTS Thirty-nine patients underwent randomization: 19 to endoscopic treatment (16 of whom underwent lithotripsy) and 20 to operative pancreaticojejunostomy. During the 24 months of follow-up, patients who underwent surgery, as compared with those who were treated endoscopically, had lower Izbicki pain scores (25 vs. 51, P<0.001) and better physical health summary scores on the Medical Outcomes Study 36-Item Short-Form General Health Survey questionnaire (P=0.003). At the end of follow-up, complete or partial pain relief was achieved in 32% of patients assigned to endoscopic drainage as compared with 75% of patients assigned to surgical drainage (P=0.007). Rates of complications, length of hospital stay, and changes in pancreatic function were similar in the two treatment groups, but patients receiving endoscopic treatment required more procedures than did patients in the surgery group (a median of eight vs. three, P<0.001). CONCLUSIONS Surgical drainage of the pancreatic duct was more effective than endoscopic treatment in patients with obstruction of the pancreatic duct due to chronic pancreatitis. (Current Controlled Trials number, ISRCTN04572410 [controlled-].).", "author" : [ { "dropping-particle" : "", "family" : "Cahen", "given" : "Djuna L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gouma", "given" : "Dirk J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nio", "given" : "Yung", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rauws", "given" : "Erik A. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boermeester", "given" : "Marja A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Busch", "given" : "Olivier R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stoker", "given" : "Jaap", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lam\u00e9ris", "given" : "Johan S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dijkgraaf", "given" : "Marcel G.W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huibregtse", "given" : "Kees", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruno", "given" : "Marco J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "New England Journal of Medicine", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2007", "2", "15" ] ] }, "page" : "676-684", "title" : "Endoscopic versus Surgical Drainage of the Pancreatic Duct in Chronic Pancreatitis", "type" : "article-journal", "volume" : "356" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(232)", "plainTextFormattedCitation" : "(232)", "previouslyFormattedCitation" : "(232)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(232), in addition to the very small sample size of the study, the overall technical success rate of ET was only 53% (maybe because ESWL and ET were not performed by the same team in the same hospital, maybe because duration of pancreatic duct stenting was limited to a 27 weeks duration) as compared to 80% (1638 / 2040) (52% - 100%) in 8 studies with comparable patients (Table 2).Pain relief assessment, based on 6 measures of the Izbicki pain score during the first 2 years after ET was reported as complete or partial in only 32% of patients (6/19).In the second RCTADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1055/s-2003-40237", "ISSN" : "0013-726X", "PMID" : "12822088", "abstract" : "BACKGROUND AND STUDY AIMS Invasive treatment for abdominal pain due to chronic pancreatitis may be either surgical or endoscopic, particularly in cases of ductal obstruction. To date, the data published on the effectiveness of these two forms of therapy have been mostly retrospective, and there have been no randomized studies. A prospective, randomized study comparing surgery with endoscopy in patients with painful obstructive chronic pancreatitis was therefore conducted. PATIENTS AND METHODS Consecutive patients with pancreatic duct obstruction and pain were invited to participate in a randomized trial comparing endotherapy and surgery, the latter consisting of resection and drainage procedures, depending on the patient's individual situation. Patients who did not agree to participation and randomization were also further assessed using the same follow-up protocol. RESULTS Of 140 eligible patients, only 72 agreed to be randomized. Surgery consisted of resection (80 %) and drainage (20 %) procedures, while endotherapy included sphincterotomy and stenting (52 %) and/or stone removal (23 %). In the entire group, the initial success rates were similar for both groups, but at the 5-year follow-up, complete absence of pain was more frequent after surgery (37 % vs. 14 %), with the rate of partial relief being similar (49 % vs. 51 %). In the randomized subgroup, results were similar (pain absence 34 % after surgery vs. 15 % after endotherapy, relief 52 % after surgery vs. 46 % after endotherapy). The increase in body weight was also greater by 20 - 25 % in the surgical group, while new-onset diabetes developed with similar frequency in both groups (34 - 43 %), again with no differences between the results for the whole group and the randomized subgroup. CONCLUSIONS Surgery is superior to endotherapy for long-term pain reduction in patients with painful obstructive chronic pancreatitis. Better selection of patients for endotherapy may be helpful in order to maximize results. Due to its low degree of invasiveness, however, endotherapy can be offered as a first-line treatment, with surgery being performed in case of failure and/or recurrence.", "author" : [ { "dropping-particle" : "", "family" : "D\u00edte", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruzicka", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zboril", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Novotn\u00fd", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Endoscopy", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2003", "7" ] ] }, "note" : "NULL", "page" : "553-558", "title" : "A Prospective, Randomized Trial Comparing Endoscopic and Surgical Therapy for Chronic Pancreatitis", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(233)", "plainTextFormattedCitation" : "(233)", "previouslyFormattedCitation" : "(233)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(233), the ET was suboptimal also as ESWL and repeated ET in case of recurrent pain were not applied. Indeed, recurrent pain attacks after ET occurred in approximately one third of patients, and was usually related to stone migration or recurrence, progressive stricturing of the MPD or pancreatic stent obstruction or dislodgmentADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1542-3565", "PMID" : "16271345", "abstract" : "BACKGROUND & AIMS The aim of this study was to evaluate the short- and long-term results of extracorporeal shockwave lithotripsy (ESWL) and endoscopic therapy for pancreatic stones. METHODS A total of 117 patients with pancreatic stones underwent ESWL and endoscopic treatment in our institute. Seventy patients who were followed-up for over 3 years after treatment were evaluated retrospectively. RESULTS Immediate pain relief was achieved in 97% and complete removal of stones was achieved in 56%. During the long-term follow-up evaluation, 49 of 70 patients continued to be asymptomatic. Pain recurred more frequently in patients with incomplete removal than in those with complete removal (P < .05). Twenty-one patients who became symptomatic during the follow-up period underwent additional therapy, and pain relief was attained without surgery in all of them. Both endocrine and exocrine function deteriorated after the long-term follow-up period (P < .05). CONCLUSIONS ESWL and endoscopic treatment of pancreatic stones proved to be effective for long-term pain relief, especially in patients in whom stones were removed completely at initial therapy.", "author" : [ { "dropping-particle" : "", "family" : "Tadenuma", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ishihara", "given" : "Takeshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamaguchi", "given" : "Taketo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsuchiya", "given" : "Shouichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kobayashi", "given" : "Akitoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakamura", "given" : "Kazuyoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sakurada", "given" : "Reiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saisho", "given" : "Hiromitsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2005", "11" ] ] }, "note" : "NULL", "page" : "1128-35", "title" : "Long-term results of extracorporeal shockwave lithotripsy and endoscopic therapy for pancreatic stones.", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(234)", "plainTextFormattedCitation" : "(234)", "previouslyFormattedCitation" : "(234)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(234). All these situations could be further managed successfully by endoscopy ESWL with a similar response rate as that for initial therapyADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1067/mge.2002.128162", "ISSN" : "0016-5107", "PMID" : "12297764", "abstract" : "BACKGROUND The aim of the study was to evaluate interventional endoscopic management of pancreatic duct stones in patients with chronic pancreatitis by describing therapeutic methods and defining factors that predict technical success. METHODS Records were retrospectively analyzed for 125 patients with symptoms caused by chronic pancreatitis with pancreatic duct stones (single 43, multiple 82) treated by interventional endoscopy, including extracorporeal shockwave lithotripsy. RESULTS Technical success was achieved in 85% of patients (11 patients by mechanical lithotripsy, 114 by piezoelectric extracorporeal shockwave lithotripsy). There were no serious complications from lithotripsy. Univariate analysis disclosed a statistically significant association between treatment success and patient age as well as prepapillary location of stones. A greater therapeutic effort was necessary in patients with stones located in the tail of the pancreas, 2 or more stones, a stone 12 mm or more in diameter, or who have had a longer duration (>8 years) of the disease. However, with exception of the last parameter, correction for multiple testing of data removed statistical significance. CONCLUSIONS Extracorporeal shockwave lithotripsy enhances endoscopic measures for treatment of pancreatic duct stones when mechanical lithotripsy fails. Middle-aged patients in the early stages of chronic pancreatitis with stones in a prepapillary location proved to be the best candidates for successful treatment. Unfavorable patient-related or morphologic factors can be compensated for through more intense efforts at therapy.", "author" : [ { "dropping-particle" : "", "family" : "Farnbacher", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schoen", "given" : "Christoph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rabenstein", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benninger", "given" : "Johannes", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hahn", "given" : "Eckhart G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schneider", "given" : "H Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastrointestinal endoscopy", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2002", "10" ] ] }, "note" : "NULL", "page" : "501-6", "title" : "Pancreatic duct stones in chronic pancreatitis: criteria for treatment intensity and success.", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(235)", "plainTextFormattedCitation" : "(235)", "previouslyFormattedCitation" : "(235)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(235). Contrary to surgery, patient’s age as well as severe co-morbidities occurring in CP such as portal hypertension are not risk factors for ET-related morbidity and mortality. Indeed, advanced age, severe co-morbidities, portal hypertension with vascular collaterals is relative or absolute contraindications for this type of surgery. Therefore, patients included in the ET group in both RCT were likely to have a poor outcome because the technical success of ET was poorADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1056/NEJMoa060610", "ISSN" : "0028-4793", "PMID" : "17301298", "abstract" : "BACKGROUND For patients with chronic pancreatitis and a dilated pancreatic duct, ductal decompression is recommended. We conducted a randomized trial to compare endoscopic and surgical drainage of the pancreatic duct. METHODS All symptomatic patients with chronic pancreatitis and a distal obstruction of the pancreatic duct but without an inflammatory mass were eligible for the study. We randomly assigned patients to undergo endoscopic transampullary drainage of the pancreatic duct or operative pancreaticojejunostomy. The primary end point was the average Izbicki pain score during 2 years of follow-up. The secondary end points were pain relief at the end of follow-up, physical and mental health, morbidity, mortality, length of hospital stay, number of procedures undergone, and changes in pancreatic function. RESULTS Thirty-nine patients underwent randomization: 19 to endoscopic treatment (16 of whom underwent lithotripsy) and 20 to operative pancreaticojejunostomy. During the 24 months of follow-up, patients who underwent surgery, as compared with those who were treated endoscopically, had lower Izbicki pain scores (25 vs. 51, P<0.001) and better physical health summary scores on the Medical Outcomes Study 36-Item Short-Form General Health Survey questionnaire (P=0.003). At the end of follow-up, complete or partial pain relief was achieved in 32% of patients assigned to endoscopic drainage as compared with 75% of patients assigned to surgical drainage (P=0.007). Rates of complications, length of hospital stay, and changes in pancreatic function were similar in the two treatment groups, but patients receiving endoscopic treatment required more procedures than did patients in the surgery group (a median of eight vs. three, P<0.001). CONCLUSIONS Surgical drainage of the pancreatic duct was more effective than endoscopic treatment in patients with obstruction of the pancreatic duct due to chronic pancreatitis. (Current Controlled Trials number, ISRCTN04572410 [controlled-].).", "author" : [ { "dropping-particle" : "", "family" : "Cahen", "given" : "Djuna L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gouma", "given" : "Dirk J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nio", "given" : "Yung", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rauws", "given" : "Erik A. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boermeester", "given" : "Marja A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Busch", "given" : "Olivier R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stoker", "given" : "Jaap", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lam\u00e9ris", "given" : "Johan S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dijkgraaf", "given" : "Marcel G.W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huibregtse", "given" : "Kees", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruno", "given" : "Marco J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "New England Journal of Medicine", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2007", "2", "15" ] ] }, "page" : "676-684", "title" : "Endoscopic versus Surgical Drainage of the Pancreatic Duct in Chronic Pancreatitis", "type" : "article-journal", "volume" : "356" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(232)", "plainTextFormattedCitation" : "(232)", "previouslyFormattedCitation" : "(232)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(232) and the optimal ET was not performedADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1056/NEJMoa060610", "ISSN" : "0028-4793", "PMID" : "17301298", "abstract" : "BACKGROUND For patients with chronic pancreatitis and a dilated pancreatic duct, ductal decompression is recommended. We conducted a randomized trial to compare endoscopic and surgical drainage of the pancreatic duct. METHODS All symptomatic patients with chronic pancreatitis and a distal obstruction of the pancreatic duct but without an inflammatory mass were eligible for the study. We randomly assigned patients to undergo endoscopic transampullary drainage of the pancreatic duct or operative pancreaticojejunostomy. The primary end point was the average Izbicki pain score during 2 years of follow-up. The secondary end points were pain relief at the end of follow-up, physical and mental health, morbidity, mortality, length of hospital stay, number of procedures undergone, and changes in pancreatic function. RESULTS Thirty-nine patients underwent randomization: 19 to endoscopic treatment (16 of whom underwent lithotripsy) and 20 to operative pancreaticojejunostomy. During the 24 months of follow-up, patients who underwent surgery, as compared with those who were treated endoscopically, had lower Izbicki pain scores (25 vs. 51, P<0.001) and better physical health summary scores on the Medical Outcomes Study 36-Item Short-Form General Health Survey questionnaire (P=0.003). At the end of follow-up, complete or partial pain relief was achieved in 32% of patients assigned to endoscopic drainage as compared with 75% of patients assigned to surgical drainage (P=0.007). Rates of complications, length of hospital stay, and changes in pancreatic function were similar in the two treatment groups, but patients receiving endoscopic treatment required more procedures than did patients in the surgery group (a median of eight vs. three, P<0.001). CONCLUSIONS Surgical drainage of the pancreatic duct was more effective than endoscopic treatment in patients with obstruction of the pancreatic duct due to chronic pancreatitis. (Current Controlled Trials number, ISRCTN04572410 [controlled-].).", "author" : [ { "dropping-particle" : "", "family" : "Cahen", "given" : "Djuna L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gouma", "given" : "Dirk J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nio", "given" : "Yung", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rauws", "given" : "Erik A. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boermeester", "given" : "Marja A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Busch", "given" : "Olivier R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stoker", "given" : "Jaap", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lam\u00e9ris", "given" : "Johan S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dijkgraaf", "given" : "Marcel G.W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huibregtse", "given" : "Kees", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruno", "given" : "Marco J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "New England Journal of Medicine", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2007", "2", "15" ] ] }, "page" : "676-684", "title" : "Endoscopic versus Surgical Drainage of the Pancreatic Duct in Chronic Pancreatitis", "type" : "article-journal", "volume" : "356" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1055/s-2003-40237", "ISSN" : "0013-726X", "PMID" : "12822088", "abstract" : "BACKGROUND AND STUDY AIMS Invasive treatment for abdominal pain due to chronic pancreatitis may be either surgical or endoscopic, particularly in cases of ductal obstruction. To date, the data published on the effectiveness of these two forms of therapy have been mostly retrospective, and there have been no randomized studies. A prospective, randomized study comparing surgery with endoscopy in patients with painful obstructive chronic pancreatitis was therefore conducted. PATIENTS AND METHODS Consecutive patients with pancreatic duct obstruction and pain were invited to participate in a randomized trial comparing endotherapy and surgery, the latter consisting of resection and drainage procedures, depending on the patient's individual situation. Patients who did not agree to participation and randomization were also further assessed using the same follow-up protocol. RESULTS Of 140 eligible patients, only 72 agreed to be randomized. Surgery consisted of resection (80 %) and drainage (20 %) procedures, while endotherapy included sphincterotomy and stenting (52 %) and/or stone removal (23 %). In the entire group, the initial success rates were similar for both groups, but at the 5-year follow-up, complete absence of pain was more frequent after surgery (37 % vs. 14 %), with the rate of partial relief being similar (49 % vs. 51 %). In the randomized subgroup, results were similar (pain absence 34 % after surgery vs. 15 % after endotherapy, relief 52 % after surgery vs. 46 % after endotherapy). The increase in body weight was also greater by 20 - 25 % in the surgical group, while new-onset diabetes developed with similar frequency in both groups (34 - 43 %), again with no differences between the results for the whole group and the randomized subgroup. CONCLUSIONS Surgery is superior to endotherapy for long-term pain reduction in patients with painful obstructive chronic pancreatitis. Better selection of patients for endotherapy may be helpful in order to maximize results. Due to its low degree of invasiveness, however, endotherapy can be offered as a first-line treatment, with surgery being performed in case of failure and/or recurrence.", "author" : [ { "dropping-particle" : "", "family" : "D\u00edte", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruzicka", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zboril", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Novotn\u00fd", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Endoscopy", "id" : "ITEM-2", "issue" : "7", "issued" : { "date-parts" : [ [ "2003", "7" ] ] }, "note" : "NULL", "page" : "553-558", "title" : "A Prospective, Randomized Trial Comparing Endoscopic and Surgical Therapy for Chronic Pancreatitis", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(232,233)", "plainTextFormattedCitation" : "(232,233)", "previouslyFormattedCitation" : "(232,233)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(232,233)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1055/s-2003-40237", "ISSN" : "0013-726X", "PMID" : "12822088", "abstract" : "BACKGROUND AND STUDY AIMS Invasive treatment for abdominal pain due to chronic pancreatitis may be either surgical or endoscopic, particularly in cases of ductal obstruction. To date, the data published on the effectiveness of these two forms of therapy have been mostly retrospective, and there have been no randomized studies. A prospective, randomized study comparing surgery with endoscopy in patients with painful obstructive chronic pancreatitis was therefore conducted. PATIENTS AND METHODS Consecutive patients with pancreatic duct obstruction and pain were invited to participate in a randomized trial comparing endotherapy and surgery, the latter consisting of resection and drainage procedures, depending on the patient's individual situation. Patients who did not agree to participation and randomization were also further assessed using the same follow-up protocol. RESULTS Of 140 eligible patients, only 72 agreed to be randomized. Surgery consisted of resection (80 %) and drainage (20 %) procedures, while endotherapy included sphincterotomy and stenting (52 %) and/or stone removal (23 %). In the entire group, the initial success rates were similar for both groups, but at the 5-year follow-up, complete absence of pain was more frequent after surgery (37 % vs. 14 %), with the rate of partial relief being similar (49 % vs. 51 %). In the randomized subgroup, results were similar (pain absence 34 % after surgery vs. 15 % after endotherapy, relief 52 % after surgery vs. 46 % after endotherapy). The increase in body weight was also greater by 20 - 25 % in the surgical group, while new-onset diabetes developed with similar frequency in both groups (34 - 43 %), again with no differences between the results for the whole group and the randomized subgroup. CONCLUSIONS Surgery is superior to endotherapy for long-term pain reduction in patients with painful obstructive chronic pancreatitis. Better selection of patients for endotherapy may be helpful in order to maximize results. Due to its low degree of invasiveness, however, endotherapy can be offered as a first-line treatment, with surgery being performed in case of failure and/or recurrence.", "author" : [ { "dropping-particle" : "", "family" : "D\u00edte", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruzicka", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zboril", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Novotn\u00fd", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Endoscopy", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2003", "7" ] ] }, "note" : "NULL", "page" : "553-558", "title" : "A Prospective, Randomized Trial Comparing Endoscopic and Surgical Therapy for Chronic Pancreatitis", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(233)", "plainTextFormattedCitation" : "(233)", "previouslyFormattedCitation" : "(233)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(233).Stenting: In 6 retrospective case seriesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1055/s-2007-1005780", "ISSN" : "0013-726X", "PMID" : "8903975", "abstract" : "BACKGROUND AND STUDY AIMS Endoscopic pancreatic stent drainage has been reported to relieve pain due to chronic pancreatitis in patients with ductal outflow obstruction. However, data regarding the long-term results, as presented here, have hitherto been lacking. PATIENTS AND METHODS Over a nine-year period, 93 patients (65 males, mean age 49 years) with narcotic-dependent pain due to chronic pancreatitis and with a dominant pancreatic duct stricture visualized by endoscopic retrograde cholangiopancreatography (ERCP), were treated by stent drainage. The duration of pain prior to treatment averaged 5.6 years. The stents were exchanged according to symptoms, and removed if the stricture was judged to be adequately dilated after stenting. RESULTS Sixty-nine patients (74%) reported complete (n = 46) or partial (n = 23) pain relief at six months. In this group of \"early responders\", 60 patients experienced sustained improvement during a mean follow-up of 4.9 years (nine had recurrent pain after a mean of 1.2 years). Stents were removed in 49 patients after a mean of 15.7 months; during a mean follow-up of 3.8 years, 36 patients remained pain-free, and 13 had a relapse of pain (11 were retreated by endoscopic drainage and subsequently became pain-free). Complications seen included mild pancreatitis (n = 4) and abscess formation secondary to stent clogging (n = 2). Most patients experienced a regression of the ductal dilation after stenting. CONCLUSION In selected patients, early responders to pancreatic stent drainage are likely to benefit over the long term. Stent removal after stricture dilation may be associated with continued pain relief.", "author" : [ { "dropping-particle" : "", "family" : "Binmoeller", "given" : "K F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jue", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seifert", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nam", "given" : "W C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Izbicki", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Soehendra", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Endoscopy", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "1995", "11", "17" ] ] }, "note" : "NULL", "page" : "638-44", "title" : "Endoscopic pancreatic stent drainage in chronic pancreatitis and a dominant stricture: long-term results.", "type" : "article-journal", "volume" : "27" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0016-5107", "PMID" : "8566639", "abstract" : "BACKGROUND Pancreatic stenting is a new nonsurgical treatment for patients with chronic pancreatitis and pain. We studied the long-term safety and efficacy of pancreatic stenting. METHODS Between 1982 and 1993, 51 patients with chronic pancreatitis and persistent pain with dominant strictures in the pancreatic duct were treated with plastic pancreatic stents. RESULTS Stent insertion was successful in 49 of 51 patients. Early complications occurred in 9 of the 51 patients (18%). Patients were followed for a median of 34 months (range 6 to 128). Nine of the 49 patients (82%) had clinical improvement. Sixteen of these 40 patients still had their stents in place. Stents were removed in 22 of the 40 patients with persistent beneficial response in all (median follow-up 28.5 months). The long-term effect of stenting could not be evaluated in the remaining 2 patients because they had a double bypass operation. Stent dysfunction occurred in 27 of the 49 patients (55%) and was successfully treated by exchanging the stent. CONCLUSIONS Pancreatic stenting was associated with minimal early complications, but stent dysfunction remained a frequent late complication. Pancreatic drainage resulted in clinical improvement in 40 of the 49 patients (82%). Twenty-two of these 40 patients maintained the beneficial response after stent removal (28.5 months).", "author" : [ { "dropping-particle" : "", "family" : "Smits", "given" : "M E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Badiga", "given" : "S M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rauws", "given" : "E A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tytgat", "given" : "G N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huibregtse", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastrointestinal endoscopy", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "1995", "11" ] ] }, "note" : "NULL", "page" : "461-7", "title" : "Long-term results of pancreatic stents in chronic pancreatitis.", "type" : "article-journal", "volume" : "42" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1007/s00464-003-8933-z", "ISSN" : "1432-2218", "PMID" : "15791364", "abstract" : "BACKGROUND Endoscopic retrograde cholangiopancreatography and stent placement are relatively new alternatives to surgery for the treatment of chronic pancreatitis. The objective of this study was to determine the efficacy of pancreatic duct stent placement for the treatment of chronic pancreatitis. METHODS This study included 89 patients treated with pancreatic stents between 1993 and 2002. The patients were contacted via telephone for a personal interview with regard to pain, medication usage, weight loss or gain, and eating patterns. Additionally, medication usage before and after treatment was documented from the Kentucky Cabinet for Health Services' electronic reporting system for narcotic use. RESULTS Of the 89 patients, 9 were deceased, 5 either refused to interview or could not be contacted, and 75 were interviewed. Significant weight gain exceeding 15 lb after treatment was experienced by 22%, whereas only 4% lost weight. A majority of the patients (68%) noted that they had less severe relapses or no relapses after treatment. The patients reported a decrease in pain level on a 10-point scale from 8.7 to 4.1 (53% decrease) after treatment. A decrease in pain medication usage was reported by 47% of the patients, and 83% considered their treatment successful. The Kentucky All Schedule Prescription Electronic Report (KASPER) was obtained before and after treatment for 55 patients. According to this statewide electronic reporting system, 63% had a documented decrease in narcotic use. CONCLUSION The findings of this study support the use of pancreatic duct stenting as an option before surgical intervention for these difficult-to-manage patients with chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Vitale", "given" : "G C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cothron", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vitale", "given" : "E A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rangnekar", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zavaleta", "given" : "C M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Larson", "given" : "G M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Binford", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hammond", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Surgical endoscopy", "id" : "ITEM-3", "issue" : "10", "issued" : { "date-parts" : [ [ "2004", "10", "26" ] ] }, "note" : "NULL", "page" : "1431-4", "title" : "Role of pancreatic duct stenting in the treatment of chronic pancreatitis.", "type" : "article-journal", "volume" : "18" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "ISSN" : "0013-726X", "PMID" : "18556820", "abstract" : "BACKGROUND AND STUDY AIMS Although it has been proved that pancreatic stenting is effective in the symptomatic management of severe chronic pancreatitis, long-term outcomes after stent removal have not been fully evaluated. PATIENTS AND METHODS A total of 100 patients (75 men, 25 women; median age 49) with severe chronic pancreatitis and pancreatic duct strictures were successfully treated for pancreatic pain using polyethylene pancreatic stents and were followed up for at least 1 year after stent removal. The stents were exchanged \"on demand\" (in cases of recurrence of pain) and a definitive stent removal was attempted on the basis of clinical and endoscopic findings. Clinical variables were retrospectively assessed as potential predictors of re-stenting. RESULTS The etiology of the chronic pancreatitis was alcoholic (77 %), idiopathic (18 %), or hereditary (5 %). Patients were followed up for a median period of 69 months (range 14 - 163 months) after study entry, including a median period of 27 months (range 12 - 126 months) after stent removal. The median duration of pancreatic stenting before stent removal was 23 months (range 2 - 134 months). After attempted definitive stent removal, 30 patients (30 %) required re-stenting within the first year of follow-up, at a median time of 5.5 months after stent removal (range 1 - 12 months), while in 70 patients (70 %) pain control remained adequate during that period. By the end of the follow-up period a total of 38 patients had required re-stenting and four ultimately underwent pancreaticojejunostomy. Pancreas divisum was the only factor significantly associated with a higher risk of re-stenting (P = 0.002). CONCLUSIONS The majority (70 %) of patients with severe chronic pancreatitis who respond to pancreatic stenting maintain this response after definitive stent removal. However, a significantly higher re-stenting rate was observed in patients with chronic pancreatitis and pancreas divisum.", "author" : [ { "dropping-particle" : "", "family" : "Eleftherladis", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dinu", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delhaye", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moine", "given" : "O", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baize", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vandermeeren", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hookey", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devi\u00e8re", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Endoscopy", "id" : "ITEM-4", "issue" : "3", "issued" : { "date-parts" : [ [ "2005", "3" ] ] }, "note" : "NULL", "page" : "223-30", "title" : "Long-term outcome after pancreatic stenting in severe chronic pancreatitis.", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1080/00365520510024098", "ISSN" : "0036-5521", "PMID" : "16373284", "abstract" : "OBJECTIVE In the past 15 years there have been tremendous advances in endoscopic management of chronic pancreatitis (CP). However, the value of endoscopic pancreatic stenting is still debatable. MATERIAL AND METHODS In 98 patients suffering from symptomatic CP (84 M, 14 F, 49+/-12, age range 23-83 years) endotherapy including temporary stenting of the pancreatic duct was performed. After final stent removal, indicating the primary end-point of endotherapy, 96 patients were followed for 35+/-28 (8 days-111) months. All data were assessed retrospectively. RESULTS As well as other endoscopic procedures, a total of 358 prostheses were inserted in the pancreatic duct and left in place for 3+/-1 (1 day-11) months. Total stent treatment time was 10+/-10 (6 days-49) months. At 46+/-27 (4-111) months after limited endotherapy, 57 patients had no need for secondary intervention, two-thirds were even without further pain sensations. In 22 patients, surgical treatment and in 17 patients further endoscopic therapy became necessary, which was significantly correlated with continued alcohol consumption. CONCLUSIONS Temporary stent placement as a part of interventional endoscopic therapy in CP shows a high rate of technical and long-term clinical success, with no need for secondary treatment in a remarkable number of patients. Continued cessation of alcohol consumption supports the treatment benefit significantly.", "author" : [ { "dropping-particle" : "", "family" : "Farnbacher", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "M\u00fchldorfer", "given" : "Steffen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wehler", "given" : "Markus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fischer", "given" : "Bernhard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hahn", "given" : "Eckhart G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schneider", "given" : "H Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of gastroenterology", "id" : "ITEM-5", "issue" : "1", "issued" : { "date-parts" : [ [ "2006", "1", "8" ] ] }, "note" : "NULL", "page" : "111-7", "title" : "Interventional endoscopic therapy in chronic pancreatitis including temporary stenting: a definitive treatment?", "type" : "article-journal", "volume" : "41" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1097/mpa.0b013e3180325ba6", "ISSN" : "1536-4828", "PMID" : "17414050", "abstract" : "OBJECTIVES Obstruction of the pancreatic duct is a common feature of chronic pancreatitis and often requires interventional therapy. The current prospective study investigated clinical success in 19 patients after initial endoscopic retrograde pancreaticography and relapse rates during a 2-year follow-up period. METHODS Seventeen of 19 patients with chronic pancreatitis (stage III according to the Cambridge classification) were treated by sphincterotomy and stent insertion. Endoscopic retrograde pancreaticography failed in 2 patients. RESULTS Strictures were cannulated, dilated, and stones were removed with a dormia basket in 13 of 17 patients. Extracorporeal shock wave lithotripsy was necessary in 5 patients. Polyethylene stents (7F-11.5F) were placed into the dilated pancreatic duct. Mean duration of internal pancreatic stenting was 5.6 months. Three of 17 patients had recurrence of pain during the first follow-up year after stent extraction; in the second follow-up year, another 2 patients had a relapse. Overall, patients' assessment of the stent therapy revealed complete satisfaction in 17 of 19 patients. CONCLUSIONS Endoscopic stent therapy is a safe, minimally invasive, and effective procedure in patients experiencing pain attacks during chronic pancreatitis associated with dilated pancreatic duct. According to our results, a relapse rate of approximately 30% can be expected within 2 years after stent extraction. These patients may be treated by repeated stent therapy.", "author" : [ { "dropping-particle" : "", "family" : "Weber", "given" : "Andreas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schneider", "given" : "Jochen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Neu", "given" : "Bruno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meining", "given" : "Alexander", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Born", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schmid", "given" : "Roland M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prinz", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreas", "id" : "ITEM-6", "issue" : "3", "issued" : { "date-parts" : [ [ "2007", "4" ] ] }, "note" : "NULL", "page" : "287-94", "title" : "Endoscopic stent therapy for patients with chronic pancreatitis: results from a prospective follow-up study.", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(236\u2013241)", "plainTextFormattedCitation" : "(236\u2013241)", "previouslyFormattedCitation" : "(236\u2013241)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(236–241) with FU 24 months, including a total of 450 patients, pain improvement was reported in 67% (301 / 450, ranging from 43% to 74% in intention-to-treat analysis) after single plastic stent removal.In the largest studyADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0013-726X", "PMID" : "18556820", "abstract" : "BACKGROUND AND STUDY AIMS Although it has been proved that pancreatic stenting is effective in the symptomatic management of severe chronic pancreatitis, long-term outcomes after stent removal have not been fully evaluated. PATIENTS AND METHODS A total of 100 patients (75 men, 25 women; median age 49) with severe chronic pancreatitis and pancreatic duct strictures were successfully treated for pancreatic pain using polyethylene pancreatic stents and were followed up for at least 1 year after stent removal. The stents were exchanged \"on demand\" (in cases of recurrence of pain) and a definitive stent removal was attempted on the basis of clinical and endoscopic findings. Clinical variables were retrospectively assessed as potential predictors of re-stenting. RESULTS The etiology of the chronic pancreatitis was alcoholic (77 %), idiopathic (18 %), or hereditary (5 %). Patients were followed up for a median period of 69 months (range 14 - 163 months) after study entry, including a median period of 27 months (range 12 - 126 months) after stent removal. The median duration of pancreatic stenting before stent removal was 23 months (range 2 - 134 months). After attempted definitive stent removal, 30 patients (30 %) required re-stenting within the first year of follow-up, at a median time of 5.5 months after stent removal (range 1 - 12 months), while in 70 patients (70 %) pain control remained adequate during that period. By the end of the follow-up period a total of 38 patients had required re-stenting and four ultimately underwent pancreaticojejunostomy. Pancreas divisum was the only factor significantly associated with a higher risk of re-stenting (P = 0.002). CONCLUSIONS The majority (70 %) of patients with severe chronic pancreatitis who respond to pancreatic stenting maintain this response after definitive stent removal. However, a significantly higher re-stenting rate was observed in patients with chronic pancreatitis and pancreas divisum.", "author" : [ { "dropping-particle" : "", "family" : "Eleftherladis", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dinu", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delhaye", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moine", "given" : "O", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baize", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vandermeeren", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hookey", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devi\u00e8re", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Endoscopy", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2005", "3" ] ] }, "note" : "NULL", "page" : "223-30", "title" : "Long-term outcome after pancreatic stenting in severe chronic pancreatitis.", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(239)", "plainTextFormattedCitation" : "(239)", "previouslyFormattedCitation" : "(239)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(239) after a median stenting duration of 23 months, 62% of patients maintained satisfactory pain control without pancreatic stent replacement during a median time of 27 months. The majority of pain recurrences, requiring a new period of pancreatic stenting occurred during the first year following stent removal (79%) with almost all (97%) having relapsed by 24 months. Consequently, if a patient remains stable during the first year after stent removal, subsequent relapse and need for re-stenting are less likely.Results of multiple plastic stenting were reported in a single study that included 19 patientsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1055/s-2005-921069", "ISSN" : "0013-726X", "PMID" : "16528652", "abstract" : "BACKGROUND AND STUDY AIMS Dominant pancreatic duct strictures located in the head of the pancreas in patients with severe chronic pancreatitis are often managed by endoscopic placement of a single plastic stent. Patients with refractory strictures after prolonged stenting require repeated stent replacement or surgical pancreaticojejunostomy. Placement of multiple plastic stents has proved effective in managing postoperative biliary strictures. The aim of this study was to investigate the feasibility, efficacy, and long-term results of multiple stenting of refractory pancreatic strictures in severe chronic pancreatitis. PATIENTS AND METHODS 19 patients with severe chronic pancreatitis (16 men, three women; mean age 45 years) and with a single pancreatic stent through a refractory dominant stricture in the pancreatic head underwent the following protocol: (i) removal of the single pancreatic stent; (ii) balloon dilation of the stricture; (iii) insertion of the maximum number of stents allowed by the stricture tightness and the pancreatic duct diameter; and (iv) removal of stents after 6 to 12 months. RESULTS The median number of stents placed through the major or minor papilla was 3, with diameters ranging from 8.5 to 11.5 Fr and length from 4 to 7 cm. Only one patient (5.5 %) had persistent stricture after multiple stenting. During a mean follow-up of 38 months after removal, 84 % of patients were asymptomatic, and 10.5 % had symptomatic stricture recurrence. No major complications were recorded. CONCLUSION Endoscopic multiple stenting of dominant pancreatic duct strictures in chronic pancreatitis is a feasible and safe technique. Multiple pancreatic stenting is promising in obtaining persistent stricture dilation on long-term follow-up in the setting of severe chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Costamagna", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulajic", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tringali", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pandolfi", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gabbrielli", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spada", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Petruzziello", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Familiari", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mutignani", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Endoscopy", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2006", "3" ] ] }, "note" : "NULL", "page" : "254-9", "title" : "Multiple stenting of refractory pancreatic duct strictures in severe chronic pancreatitis: long-term results.", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(242)", "plainTextFormattedCitation" : "(242)", "previouslyFormattedCitation" : "(242)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(242). A median number of 3 simultaneous stents were left in place during 7 months. At a mean FU of 38 months following stents removal, 84% (16/19) of the patients remained free of pain.For refractory MPD stricture, the temporary insertion of fully-covered self-expandable metallic stent (FC-SEMS) could be an option (Table 5). While uncovered and partially covered SEMS have provided disappointing resultsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1052-5157", "PMID" : "10390335", "abstract" : "Among patients with advanced chronic pancreatitis and morphologically demonstrable main pancreatic duct (MPD) abnormalities who are candidates for endotherapy, about two-thirds have a MPD stricture and require stenting to achieve appropriate ductal decompression. The standard stent used in this indication is the plastic stent, which provides a median patency rate of 6 to 12 months. The requirement for stent exchange represents a limitation for the treatment of this relatively young patient population. By analogy with the biliary tract, the authors hypothesize that self-expandable metal stents might offer a long-lasting drainage of the MPD. Several years ago the authors used such stents on an experimental basis to treat patients with MPD strictures. Although routine use of self-expandable metal stents should be discouraged, the authors propose some guidelines for further technical improvement.", "author" : [ { "dropping-particle" : "", "family" : "Eisendrath", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devi\u00e8re", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastrointestinal endoscopy clinics of North America", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "1999", "7" ] ] }, "note" : "NULL", "page" : "547-54", "title" : "Expandable metal stents for benign pancreatic duct obstruction.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(243)", "plainTextFormattedCitation" : "(243)", "previouslyFormattedCitation" : "(243)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(243), 4 recent studiesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.gie.2008.07.027", "ISSN" : "1097-6779", "PMID" : "19028228", "abstract" : "BACKGROUND Painful chronic pancreatitis with main pancreatic ductal strictures is usually managed with endotherapy with a plastic stent. To date, the role of placement of metallic stents, especially uncovered ones in benign pancreatic ductal stricture, has been unsatisfactory as a result of stent dysfunction related to mucosal hyperplasia. OBJECTIVE We explored the feasibility and safety of temporary placement of a newly designed, fully covered self-expandable metal stent (FCSEMS) in painful chronic pancreatitis and refractory benign pancreatic ductal strictures. DESIGN A prospective pilot and feasibility study. SETTING A tertiary academic center. PATIENTS Thirteen patients with chronic painful pancreatitis of alcoholic (8) or idiopathic (5) etiology. INTERVENTION ERCP with temporary FCSEMS placement (2 months). Endoscopic removal of FCSEMSs was performed with a snare or rat-tooth forceps. MAIN OUTCOME MEASUREMENTS End points were feasibility, safety, and morbidity. RESULTS Successful FCSEMS placement was performed in all enrolled patients. After immediate placement of FCSEMS, 2 patients had mild acute pancreatitis related mainly to the stricture dilation procedure (Soehendra stent retriever or balloon dilation). Complications associated with stent placement included 5 migrations (39%, 1 proximal and 4 distal) and 2 incidents of cholestatic liver dysfunction associated with the compression of the bile duct orifice by expansion of FCSEMSs. In 1 patient with proximal migration, the stent was repositioned by an inflated retrieval balloon. Additional endoscopic biliary sphincterotomy with or without biliary stenting was performed in 2 patients with cholestatic liver dysfunction. There was no occurrence of pancreatic sepsis among any patients. FCSEMSs were removed from 9 of 9 patients without stent migration (100% [9/9] as per protocol, and 69% [9/13] as intention to treat, respectively). Improvement or resolution of the pancreatic ductal strictures was confirmed in all 13 patients on follow-up ERCP (2 months after stent placement), regardless of stent migration. LIMITATIONS Small patient populations without long-term follow-up. CONCLUSIONS Two-month placement of FCSEMSs in patients with refractory benign pancreatic ductal strictures may be feasible and relatively safe. However, stent migration was not uncommon. A further investigation with ideal stent design may therefore be needed before recommending FCSEMSs as a therapeutic option for refractory benign pa\u2026", "author" : [ { "dropping-particle" : "", "family" : "Park", "given" : "Do Hyun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Myung-Hwan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moon", "given" : "Sung-Hoon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Sang Soo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seo", "given" : "Dong-Wan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Sung-Koo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastrointestinal endoscopy", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2008", "12" ] ] }, "note" : "NULL", "page" : "1182-9", "title" : "Feasibility and safety of placement of a newly designed, fully covered self-expandable metal stent for refractory benign pancreatic ductal strictures: a pilot study (with video).", "type" : "article-journal", "volume" : "68" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.gie.2008.06.011", "ISSN" : "1097-6779", "PMID" : "19028226", "abstract" : "BACKGROUND Pancreatic duct (PD) stenting is beneficial for the treatment of pain in patients with PD strictures associated with chronic pancreatitis. Placement of metal stents has been reported but failed secondary to hyperplasia or migration. OBJECTIVE To investigate the outcome of patients with symptomatic and refractory PD strictures who had temporary placement of a covered self-expandable metal stent (CSEMS). DESIGN Patients with refractory PD strictures were offered temporary CSEMS placement. Pain scores were evaluated before and after CSEMS placement. SETTING A tertiary-care center. PATIENTS Six patients (4 men, mean age +/- SD 55 +/- 8 years) received a CSEMS, and 5 patients had removal of a CSEMS after a mean time of 92 days. INTERVENTION Placement of CSEMS (8-mm or 10-mm diameter VIABIL) in the PD, with removal after 3 months. MAIN OUTCOME MEASUREMENTS The pain score before and after stent placement and the sustained response after removal. Morbidity associated with stent placement and removal was also noted. RESULTS Pain scores after CSEMS placement significantly improved (P = .024), from 6.4 to 1.6. Of the 5 patients who underwent CSEMS removal, 3 developed recurrent symptomatic pancreatic stricture, of whom 2 required repeat stenting with a larger-diameter CSEMS (10 mm) and 2 remained pain free. The CSEMS was not removed in 1 patient because pancreatic malignancy was diagnosed. There were no complications during placement or removal of CSEMSs. LIMITATION This was a pilot study. CONCLUSION Temporary placement of CSEMSs in patients with symptomatic refractory PD stricture offers transient relief of pain. Further investigation is needed to determine the optimal diameter and duration of placement.", "author" : [ { "dropping-particle" : "", "family" : "Sauer", "given" : "Bryan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Talreja", "given" : "Jayant", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ellen", "given" : "Kristi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ku", "given" : "Jennifer", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shami", "given" : "Vanessa M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kahaleh", "given" : "Michel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastrointestinal endoscopy", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2008", "12" ] ] }, "note" : "NULL", "page" : "1173-8", "title" : "Temporary placement of a fully covered self-expandable metal stent in the pancreatic duct for management of symptomatic refractory chronic pancreatitis: preliminary data (with videos).", "type" : "article-journal", "volume" : "68" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.gie.2010.01.063", "ISSN" : "1097-6779", "PMID" : "20493483", "abstract" : "BACKGROUND Fully covered self-expandable metal stent (FCSEMS) placement has recently been tried in the management of refractory pancreatic-duct strictures associated with advanced chronic pancreatitis. The major limitation of FCSEMSs was frequent migration. OBJECTIVE To assess the safety, migration rate, and removability of modified FCSEMSs with antimigration features used for the treatment of benign pancreatic-duct strictures. DESIGN Prospective study. SETTING Tertiary academic center. PATIENTS Thirty-two patients with chronic painful pancreatitis and dominant ductal stricture. INTERVENTIONS Transpapillary endoscopic placement of FCSEMSs in the pancreatic duct with removal after 3 months. MAIN OUTCOME MEASUREMENTS Technical and functional success and adverse events associated with the placement of metal stents. RESULTS FCSEMSs were successfully placed in all patients through the major (n = 27) or minor (n = 5) duodenal papilla. All patients achieved pain relief from stent placement. There was no occurrence of stent-induced pancreatitis or pancreatic sepsis. No stent migrated, and all stents were easily removed. Follow-up ERCP 3 months after stent placement showed resolution of duct strictures in all patients. Pancreatograms obtained at FCSEMS removal displayed de novo focal pancreatic duct strictures in 5 patients, but all were asymptomatic. LIMITATIONS No long-term follow-up. CONCLUSIONS Temporary 3-month placement of FCSEMSs was effective in resolving pancreatic-duct strictures in chronic pancreatitis, with an acceptable morbidity profile. Modified FCSEMSs can prevent stent migration, but may be associated with de novo duct strictures. Further trials are needed to assess long-term safety and efficacy.", "author" : [ { "dropping-particle" : "", "family" : "Moon", "given" : "Sung-Hoon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Myung-Hwan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Park", "given" : "Do Hyun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Song", "given" : "Tae Joon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eum", "given" : "Junbum", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Sang Soo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seo", "given" : "Dong Wan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Sung Koo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastrointestinal endoscopy", "id" : "ITEM-3", "issue" : "1", "issued" : { "date-parts" : [ [ "2010", "7" ] ] }, "note" : "NULL", "page" : "86-91", "title" : "Modified fully covered self-expandable metal stents with antimigration features for benign pancreatic-duct strictures in advanced chronic pancreatitis, with a focus on the safety profile and reducing migration.", "type" : "article-journal", "volume" : "72" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1055/s-0032-1309774", "ISSN" : "1438-8812", "PMID" : "22826158", "abstract" : "Fully covered self-expanding metal stents (FC-SEMSs), which can be removed from the bile duct, have recently been used in the main pancreatic duct (MPD) in chronic pancreatitis. The aim of this study was to investigate the feasibility, safety, and efficacy of FC-SEMSs in painful chronic pancreatitis with refractory pancreatic strictures. The primary endpoints were technical success and procedure-related morbidity. Secondary endpoints were pain relief at the end of follow-up and resolution of the dominant pancreatic stricture at endoscopic retrograde pancreatography. Over 5 months, 10 patients with painful chronic pancreatitis and refractory dominant pancreatic duct strictures were treated with FC-SEMSs. All FC-SEMSs were successfully released and removed, although two stents were embedded in the MPD at their distal end and treated endoscopically without complications. Mild abdominal pain was noted in three patients after stent release. During treatment, pain relief was achieved in nine patients, but one continued to take morphine, because of addiction. Cholestasis developed in two patients and was treated endoscopically; no patient developed acute pancreatitis or pancreatic sepsis. After stent removal, the diameter of the narrowest MPD stricture had increased significantly from 3.5 mm to 5.8 mm. Patients were followed up for a mean of 19.8 months: two patients who continued drinking alcohol presented with mild acute pancreatitis; one patient developed further chronic pancreatic pain; and one had a transient pain episode. At the end of the study, nine patients no longer had chronic pain and no patients had required surgery. Endoscopic treatment of refractory MPD stricture in chronic pancreatitis by placement of an FC-SEMS appears feasible, safe, and potentially effective.", "author" : [ { "dropping-particle" : "", "family" : "Giacino", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grandval", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laugier", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Endoscopy", "id" : "ITEM-4", "issue" : "9", "issued" : { "date-parts" : [ [ "2012", "9", "23" ] ] }, "note" : "NULL", "page" : "874-7", "title" : "Fully covered self-expanding metal stents for refractory pancreatic duct strictures in chronic pancreatitis.", "type" : "article-journal", "volume" : "44" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(244\u2013247)", "plainTextFormattedCitation" : "(244\u2013247)", "previouslyFormattedCitation" : "(244\u2013247)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(244–247) have reported pain improvement in 53/61 patients (87%) but with a short FU after stent removal.Interestingly, a recent systematic review suggested that FC SEMS provide similar good results as multiple plastic stentsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.pan.2013.12.005", "ISSN" : "14243903", "PMID" : "24650959", "abstract" : "BACKGROUND AND AIMS Refractory chronic pancreatitis has been proposed as a challenge for endoscopists following routine single plastic stenting. However, data on the efficacy and safety of further endoscopic stenting are still controversial. The current systematic review aimed to assess the efficacy and safety of placement of fully covered self-expandable metal stent (FCSEMS) and multiple plastic stents. METHODS Databases including MEDLINE, EMBASE, the Cochrane Library, CBM, CNKI, VIP, and WANFANG Database were used to search relevant trials. Published studies were assessed by using well-defined inclusion and exclusion criteria. The process was independently performed by two investigators. RESULTS A total of 5 studies provided data of 80 patients. Forest plots and publication bias were not carried out because few studies were relevant and screened studies were all case series. The technical success rate was 100% both in placement of FCSEMS and multiple plastic stents. The functional success rate after placement of FCSEMS was 100%, followed by multiple plastic stents (94.7%). Complications occurred 26.2% after FCSEMS placement, which was not described in detail in multiple plastic stents. The stent migration rate was 8.2% for FCSEMS and 10.5% for multiple plastic stents. Reintervention rate was 9.8% for FCSEMS and 15.8% for multiple plastic stents. Pain improvement rate was 85.2% for FCSEMS and 84.2% for multiple plastic stents. CONCLUSIONS FCSEMS appeared to be no significant difference with multiple plastic stents in treatment of refractory chronic pancreatitis. We need to develop more investigations.", "author" : [ { "dropping-particle" : "", "family" : "Shen", "given" : "Yonghua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Mingdong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Min", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Yunhong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lu", "given" : "Ying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zou", "given" : "Xiaoping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreatology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2014", "3" ] ] }, "note" : "NULL", "page" : "87-90", "title" : "Covered metal stent or multiple plastic stents for refractory pancreatic ductal strictures in chronic pancreatitis: A systematic review", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(248)", "plainTextFormattedCitation" : "(248)", "previouslyFormattedCitation" : "(248)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(248).Factors predicting favorable clinical outcome after ET ESWL have been identified:Immediate pain relief or improvement after ET was significantly associated with technical success (successful decompression of the MPD as suggested by a decrease in MPD diameter or a complete / partial duct clearance) and a low frequency of pain attacks before ETADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0016-5085", "PMID" : "1732129", "abstract" : "Extracorporeal shock-wave lithotripsy (ESWL) has been used to disintegrate pancreatic stones located in the main pancreatic duct for 123 patients with severe chronic pancreatitis. Endoscopic management following ESWL is aimed at restoring the pancreatic flow to the duodenum. Stone disintegration was achieved in 122 patients, whereas a decrease in the main pancreatic duct diameter resulted in 111, and complete clearance of the main pancreatic duct was obtained in 72. Pain relief, complete (40/88) or partial (35/88), correlated significantly with the results of the endoscopic drainage of the main pancreatic duct (e.g., decrease in main pancreatic duct diameter). Relapsing pain was most often related to recurrent pancreatic duct obstruction. Of 76 patients whose body weight had decreased before ESWL, 54 gained weight. Improvement of the exocrine function, evaluated by the [14C]triolein breath test before and 11 months, on the average, after ESWL, was observed in 12 patients among 22 for whom this test was performed before and after treatment. Improvement of the endocrine function after relief of obstruction of the main pancreatic duct was less frequently recorded (4/41). ESWL of pancreatic stones is a new, safe, and highly effective method of facilitating the endoscopic procedures for relief of pancreatic duct obstruction in severe chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Delhaye", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vandermeeren", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baize", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cremer", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "1992", "2" ] ] }, "note" : "NULL", "page" : "610-20", "title" : "Extracorporeal shock-wave lithotripsy of pancreatic calculi.", "type" : "article-journal", "volume" : "102" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0017-5749", "PMID" : "1644340", "abstract" : "Extracorporeal shock wave lithotripsy of pancreatic duct stones (largest stone 12 (SD) 6 mm) was performed in 24 patients with abdominal pain and a dilated duct system (main pancreatic duct 10 (3) mm). The procedure was well tolerated in all but two patients, who had a mild pancreatitic attack immediately after lithotripsy. Disintegration of the stones was achieved in 21 patients. This allowed complete clearance of the duct system by an endoscopic approach in 10 (42%) patients and partial clearance in 7 (29%) patients. Within a mean follow up period of 24 (14) months half of the patients showed complete or considerable relief of pain and alleviation of symptoms was achieved in seven patients. Relief of pain occurred more often after complete ductal clearance. There were no fatalities within the follow up period. These findings underline the value of a combined non-surgical approach, using endoscopy and adjuvant shock wave lithotripsy to patients with large pancreatic calculi and pain attacks.", "author" : [ { "dropping-particle" : "", "family" : "Sauerbruch", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holl", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sackmann", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Paumgartner", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gut", "id" : "ITEM-2", "issue" : "7", "issued" : { "date-parts" : [ [ "1992", "7" ] ] }, "note" : "NULL", "page" : "969-72", "title" : "Extracorporeal lithotripsy of pancreatic stones in patients with chronic pancreatitis and pain: a prospective follow up study.", "type" : "article-journal", "volume" : "33" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISSN" : "0016-5107", "PMID" : "8781931", "abstract" : "BACKGROUND In severe chronic pancreatitis associated with intraductal stones, therapeutic endoscopy aims to reduce increased intraductal pressure by pancreatic sphincterotomy and stone clearance. METHODS Results of treatment were evaluated in 70 new patients who underwent pancreatic sphincterotomy and attempted stone removal. Technical results and frequency of pain relief and recurrence are compared. RESULTS Complete ductal clearance of calculi was obtained in 50% of cases. Immediate clinical improvement occurred in 95% of patients with painful attacks. No severe complications or mortality occurred. Fifty-four percent of all patients with painful chronic pancreatitis did not experience any pain recurrence within 2 years. Associations found to be statistically significant by multivariate analysis were ductal clearance and extracorporeal shock wave lithotripsy, pain disappearance and ductal clearance, pain recurrence and long evolution, and severe disease before treatment and presence of a ductal substenosis. CONCLUSIONS In this subset of patients our results indicate that the pain of chronic pancreatitis is mainly related to increased intraductal pressure. Endoscopic management appears to be a safe, conservative, alternative to surgery. The best results are obtained when it is performed early in the course of calcifying chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Dumonceau", "given" : "J M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devi\u00e8re", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moine", "given" : "O", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delhaye", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vandermeeren", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baize", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gansbeke", "given" : "D", "non-dropping-particle" : "Van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cremer", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastrointestinal endoscopy", "id" : "ITEM-3", "issue" : "6", "issued" : { "date-parts" : [ [ "1996", "6" ] ] }, "note" : "NULL", "page" : "547-55", "title" : "Endoscopic pancreatic drainage in chronic pancreatitis associated with ductal stones: long-term results.", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1111/j.1572-0241.2000.03190.x", "ISSN" : "0002-9270", "PMID" : "11151873", "abstract" : "OBJECTIVE Therapeutic endoscopy may be effective in selected patients with chronic calcific pancreatitis (CCP). We prospectively evaluated the early outcome of extracorporeal shockwave lithotripsy (ESWL) in combination with interventional endoscopy, using broad inclusion criteria. METHODS A total of 48 consecutive patients (35 male, 13 female) were recruited for ESWL and endoscopic therapy of symptomatic CCP. Symptoms, quality of life, pancreatic morphology and function were assessed before and after. RESULTS Multiple stones (n = 43), strictures (n = 34), and pancreas divisum (n = 11) were found. A median of 13 ESWL sessions (range 2-74) with a median of 22,100 shockwaves (1,700-150,900) were required. Endoscopic pancreatic sphincterotomy (n = 48), stricture dilation (n = 12), and/or stenting (n = 27) were performed. After therapy, drainage of the pancreatic duct system was achieved in 36, complete stone clearance in 21 patients. Follow-up (n = 38) at 7 months (range 5-9) showed a significant decrease in pancreatic duct diameter (p < 0.001) and pain score (p < 0.0001) whereas complete pain relief was observed in 45% of cases. Several quality of life scores improved significantly. Weight gain occurred in 68% of patients. Normalization of fasting blood glucose and HbA1c levels were observed in four patients, without modifying their treatment. Improvement in pain score correlated with weight gain and decrease in pancreatic duct diameter. Nonalcoholic etiology was associated with a better chance for improvement in pain score and decrease in pancreatic duct diameter. The presence of strictures did not deteriorate the clinical outcome. CONCLUSIONS Besides pain relief, ESWL in combination with interventional endoscopy resulted in pancreatic ductal decompression, weight gain, and improvement in quality of life in a considerable number of patients with advanced CCP.", "author" : [ { "dropping-particle" : "", "family" : "Brand", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kahl", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sidhu", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nam", "given" : "V C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Sriram", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jaeckle", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thonke", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Soehendra", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American journal of gastroenterology", "id" : "ITEM-4", "issue" : "12", "issued" : { "date-parts" : [ [ "2000", "12" ] ] }, "note" : "NULL", "page" : "3428-38", "title" : "Prospective evaluation of morphology, function, and quality of life after extracorporeal shockwave lithotripsy and endoscopic treatment of chronic calcific pancreatitis.", "type" : "article-journal", "volume" : "95" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(249\u2013252)", "plainTextFormattedCitation" : "(249\u2013252)", "previouslyFormattedCitation" : "(249\u2013252)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(249–252) (Table 1).Medium-term clinical improvement correlated with low-frequency of pain attacks before treatment (Type A pain pattern according to Ammann RW et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0016-5085", "PMID" : "10220505", "abstract" : "BACKGROUND & AIMS The pain pattern of chronic pancreatitis (CP) and its surgical implications are discussed. The aim of this study was to (1) define typical pain patterns, (2) correlate pain patterns with the presumptive causes of the pain, and (3) compare the natural history of patients treated conservatively or surgically with respect to pain relief, pancreatic dysfunction, and clinical outcome. METHODS A cohort in this prospective long-term study included 207 patients with alcoholic CP (91 without and 116 with surgery for pain relief). A clinically based staging system was applied to characterize pain in the evolution from onset to end-stage CP. RESULTS Average duration of CP was 17 years. In early-stage CP, episodes of recurrent (acute) pancreatitis predominated. Chronic pain was typically associated with local complications (mainly pseudocysts, 84 of 155; 54%), relieved definitely by a single (drainage) procedure in approximately two thirds of patients. Additional surgery was required for late pain recurrence in 39 patients (34%), primarily symptomatic cholestasis (18 of 39; 46%). All patients achieved complete pain relief in advanced CP. CONCLUSIONS In our experience, relief of chronic pain regularly follows selective surgery tailored to the presumptive pain cause or occurs spontaneously in uncomplicated advanced CP.", "author" : [ { "dropping-particle" : "", "family" : "Ammann", "given" : "R W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muellhaupt", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "1999", "5" ] ] }, "note" : "NULL", "page" : "1132-40", "title" : "The natural history of pain in alcoholic chronic pancreatitis.", "type" : "article-journal", "volume" : "116" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(8)", "plainTextFormattedCitation" : "(8)", "previouslyFormattedCitation" : "(8)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(8)), short duration of disease before treatment, and absence of MPD strictureADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1055/s-2007-1005780", "ISSN" : "0013-726X", "PMID" : "8903975", "abstract" : "BACKGROUND AND STUDY AIMS Endoscopic pancreatic stent drainage has been reported to relieve pain due to chronic pancreatitis in patients with ductal outflow obstruction. However, data regarding the long-term results, as presented here, have hitherto been lacking. PATIENTS AND METHODS Over a nine-year period, 93 patients (65 males, mean age 49 years) with narcotic-dependent pain due to chronic pancreatitis and with a dominant pancreatic duct stricture visualized by endoscopic retrograde cholangiopancreatography (ERCP), were treated by stent drainage. The duration of pain prior to treatment averaged 5.6 years. The stents were exchanged according to symptoms, and removed if the stricture was judged to be adequately dilated after stenting. RESULTS Sixty-nine patients (74%) reported complete (n = 46) or partial (n = 23) pain relief at six months. In this group of \"early responders\", 60 patients experienced sustained improvement during a mean follow-up of 4.9 years (nine had recurrent pain after a mean of 1.2 years). Stents were removed in 49 patients after a mean of 15.7 months; during a mean follow-up of 3.8 years, 36 patients remained pain-free, and 13 had a relapse of pain (11 were retreated by endoscopic drainage and subsequently became pain-free). Complications seen included mild pancreatitis (n = 4) and abscess formation secondary to stent clogging (n = 2). Most patients experienced a regression of the ductal dilation after stenting. CONCLUSION In selected patients, early responders to pancreatic stent drainage are likely to benefit over the long term. Stent removal after stricture dilation may be associated with continued pain relief.", "author" : [ { "dropping-particle" : "", "family" : "Binmoeller", "given" : "K F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jue", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seifert", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nam", "given" : "W C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Izbicki", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Soehendra", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Endoscopy", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "1995", "11", "17" ] ] }, "note" : "NULL", "page" : "638-44", "title" : "Endoscopic pancreatic stent drainage in chronic pancreatitis and a dominant stricture: long-term results.", "type" : "article-journal", "volume" : "27" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0016-5107", "PMID" : "8781931", "abstract" : "BACKGROUND In severe chronic pancreatitis associated with intraductal stones, therapeutic endoscopy aims to reduce increased intraductal pressure by pancreatic sphincterotomy and stone clearance. METHODS Results of treatment were evaluated in 70 new patients who underwent pancreatic sphincterotomy and attempted stone removal. Technical results and frequency of pain relief and recurrence are compared. RESULTS Complete ductal clearance of calculi was obtained in 50% of cases. Immediate clinical improvement occurred in 95% of patients with painful attacks. No severe complications or mortality occurred. Fifty-four percent of all patients with painful chronic pancreatitis did not experience any pain recurrence within 2 years. Associations found to be statistically significant by multivariate analysis were ductal clearance and extracorporeal shock wave lithotripsy, pain disappearance and ductal clearance, pain recurrence and long evolution, and severe disease before treatment and presence of a ductal substenosis. CONCLUSIONS In this subset of patients our results indicate that the pain of chronic pancreatitis is mainly related to increased intraductal pressure. Endoscopic management appears to be a safe, conservative, alternative to surgery. The best results are obtained when it is performed early in the course of calcifying chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Dumonceau", "given" : "J M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devi\u00e8re", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moine", "given" : "O", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delhaye", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vandermeeren", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baize", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gansbeke", "given" : "D", "non-dropping-particle" : "Van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cremer", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastrointestinal endoscopy", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "1996", "6" ] ] }, "note" : "NULL", "page" : "547-55", "title" : "Endoscopic pancreatic drainage in chronic pancreatitis associated with ductal stones: long-term results.", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.cgh.2011.12.040", "ISSN" : "1542-7714", "PMID" : "22245964", "abstract" : "BACKGROUND & AIMS Endoscopic therapy (ET) frequently is used to treat patients with painful chronic pancreatitis (CP), but little is known about outcomes of patients for whom ET was not successful who then underwent surgery, or outcomes after ET compared with only medical treatment. We evaluated use and long-term effectiveness of ET in a well-defined cohort of patients with CP. METHODS We analyzed data from 146 patients with CP who participated in the North American Pancreatitis Study 2 at the University of Pittsburgh Medical Center from 2000 to 2006; 71 (49%) patients received ET at the University of Pittsburgh Medical Center. Success of ET and surgery were defined by cessation of narcotic therapy and resolution of episodes of acute pancreatitis. Disease progression was followed up from its onset until January 1, 2011 (mean, 8.2 \u00b1 4.7 y). RESULTS Patients who underwent ET had more symptoms (pain, recurrent pancreatitis) and had more complex pancreatic morphology (based on imaging) than patients who received medical therapy. ET had a high rate of technical success (60 of 71 cases; 85%); its rates of clinical success were 51% for 28 of 55 patients for whom follow-up data were available (mean time, 4.8 \u00b1 3.0 y) and 50% for 12 of 24 patients who underwent surgery after receiving ET. Patients who responded to ET were significantly older, had a shorter duration of disease before ET, had less constant pain, and required fewer daily narcotics than patients who did not respond to ET. Among the 36 symptomatic patients who received medical therapy and were followed up for a mean period of 5.7 \u00b1 4.1 years, 31% improved and 53% had no change in symptoms; of these, 21% underwent surgery. CONCLUSIONS ET is clinically successful for 50% of patients with symptomatic CP. When ET is not successful, surgery has successful outcomes in 50% of patients. Symptoms resolve in 31% of symptomatic patients who receive only medical therapy.", "author" : [ { "dropping-particle" : "", "family" : "Clarke", "given" : "Bridger", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slivka", "given" : "Adam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tomizawa", "given" : "Yutaka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanders", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Papachristou", "given" : "Georgios I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Whitcomb", "given" : "David C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yadav", "given" : "Dhiraj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association", "id" : "ITEM-3", "issue" : "7", "issued" : { "date-parts" : [ [ "2012", "7" ] ] }, "note" : "NULL", "page" : "795-802", "title" : "Endoscopic therapy is effective for patients with chronic pancreatitis.", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1097/MPA.0000000000000140", "ISSN" : "1536-4828", "PMID" : "24717828", "abstract" : "OBJECTIVE The aim of this study was to evaluate the M-ANNHEIM classification system to categorize patients with chronic pancreatitis (CP). METHODS All symptomatic patients recruited from the gastroenterology outpatient clinic of Changhai Hospital (n = 89) were routinely evaluated by magnetic resonance cholangiopancreatography and contrast-enhanced computed tomography. M-ANNHEIM clinical staging was used to categorize patients. The primary outcome measure was pain during the 2-year follow-up period, expressed as mean Izbicki pain scores obtained before and after endotherapy. RESULTS There was a significant improvement in mean (SD) Izbicki pain scores obtained at 24 months among patients receiving endoscopic therapy at stage 1a compared with those at stage 1b (4.9 [3.0] vs 14.5 [6.9], P = 0.012). Furthermore, significantly more patients receiving endoscopic therapy at stage 1a achieved complete + partial pain relief after 2-year follow-up than those at stage 1b (95.2% vs 78.0%, P = 0.021). There was no exocrine or endocrine insufficiency, but a significantly greater number of patients treated at stage 1a had post-endoscopic retrograde cholangiopancreatography pancreatitis compared with those at stage 1b (10.5% vs 2.7%, P = 0.025). CONCLUSIONS We demonstrated that a sophisticated M-ANNHEIM classification system for CP will improve diagnosis by allowing for more timely intervention. Furthermore, prompt treatment of CP may achieve improved pain relief and patient outcomes.", "author" : [ { "dropping-particle" : "", "family" : "He", "given" : "Yuan-Xiang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Hong-Wei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sun", "given" : "Xiao-Tian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ye", "given" : "Zhou", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Wei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lai", "given" : "Xiao-Wei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Xin-Tao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Liang-Hao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sun", "given" : "Chang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liao", "given" : "Zhuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Zhao-Shen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreas", "id" : "ITEM-4", "issue" : "6", "issued" : { "date-parts" : [ [ "2014", "8" ] ] }, "note" : "NULL", "page" : "829-33", "title" : "Endoscopic management of early-stage chronic pancreatitis based on M-ANNHEIM classification system: a prospective study.", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(236,251,253,254)", "plainTextFormattedCitation" : "(236,251,253,254)", "previouslyFormattedCitation" : "(236,251,253,254)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(236,251,253,254) (Tables 2 and 4). Note that in the RCT from Cahen et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1056/NEJMoa060610", "ISSN" : "0028-4793", "PMID" : "17301298", "abstract" : "BACKGROUND For patients with chronic pancreatitis and a dilated pancreatic duct, ductal decompression is recommended. We conducted a randomized trial to compare endoscopic and surgical drainage of the pancreatic duct. METHODS All symptomatic patients with chronic pancreatitis and a distal obstruction of the pancreatic duct but without an inflammatory mass were eligible for the study. We randomly assigned patients to undergo endoscopic transampullary drainage of the pancreatic duct or operative pancreaticojejunostomy. The primary end point was the average Izbicki pain score during 2 years of follow-up. The secondary end points were pain relief at the end of follow-up, physical and mental health, morbidity, mortality, length of hospital stay, number of procedures undergone, and changes in pancreatic function. RESULTS Thirty-nine patients underwent randomization: 19 to endoscopic treatment (16 of whom underwent lithotripsy) and 20 to operative pancreaticojejunostomy. During the 24 months of follow-up, patients who underwent surgery, as compared with those who were treated endoscopically, had lower Izbicki pain scores (25 vs. 51, P<0.001) and better physical health summary scores on the Medical Outcomes Study 36-Item Short-Form General Health Survey questionnaire (P=0.003). At the end of follow-up, complete or partial pain relief was achieved in 32% of patients assigned to endoscopic drainage as compared with 75% of patients assigned to surgical drainage (P=0.007). Rates of complications, length of hospital stay, and changes in pancreatic function were similar in the two treatment groups, but patients receiving endoscopic treatment required more procedures than did patients in the surgery group (a median of eight vs. three, P<0.001). CONCLUSIONS Surgical drainage of the pancreatic duct was more effective than endoscopic treatment in patients with obstruction of the pancreatic duct due to chronic pancreatitis. (Current Controlled Trials number, ISRCTN04572410 [controlled-].).", "author" : [ { "dropping-particle" : "", "family" : "Cahen", "given" : "Djuna L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gouma", "given" : "Dirk J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nio", "given" : "Yung", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rauws", "given" : "Erik A. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boermeester", "given" : "Marja A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Busch", "given" : "Olivier R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stoker", "given" : "Jaap", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lam\u00e9ris", "given" : "Johan S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dijkgraaf", "given" : "Marcel G.W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huibregtse", "given" : "Kees", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruno", "given" : "Marco J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "New England Journal of Medicine", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2007", "2", "15" ] ] }, "page" : "676-684", "title" : "Endoscopic versus Surgical Drainage of the Pancreatic Duct in Chronic Pancreatitis", "type" : "article-journal", "volume" : "356" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(232)", "plainTextFormattedCitation" : "(232)", "previouslyFormattedCitation" : "(232)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(232), Type A pain pattern was recorded in only 37% of the patients randomized in the ET group and 16/19 (84%) presented with a MPD stricture.Long-term clinical success was associated with a short duration of disease before treatment, absence of ongoing smoking at the end of FU, a shorter duration of ET and a lower number of ERCP proceduresADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1542-3565", "PMID" : "15625655", "abstract" : "BACKGROUND & AIMS Endotherapy for patients with painful chronic pancreatitis (CP) gives early and midterm clinical results comparable with those of conventional surgery. The authors evaluated long-term clinical outcome after endoscopic pancreatic ductal drainage, focusing on pain and pancreatic endocrine/exocrine functions. METHODS Of 110 patients with painful CP endoscopically treated between October 1987 and December 1989, 56 long-surviving patients were followed-up for 14.4 years (SD, .6 y); 40 patients died and 14 patients were lost to follow-up evaluation. Technical results included decreased ductal dilation and stone clearance. Clinical results included the rate of hospitalizations for pain before and after endotherapy, the need for surgery, the course of endocrine/exocrine insufficiencies, and late mortality. RESULTS Complete or partial technical success initially was obtained in 48 of 56 long-surviving patients. Long-term clinical success (< or =5 hospitalizations for pain during follow-up evaluation, without surgery) was obtained for 37 of 56 patients. At a mean follow-up time of 14.4 years, 44 patients had avoided surgery and the annual rate of hospitalizations for pain decreased significantly (before endotherapy: 0.98 [+/-1.36] vs 0.40 [+/-0.51] for the 3 years thereafter vs 0.14 [+/-0.22] for the last 11 years of follow-up evaluation; P < .001). Short duration of disease before initial therapy and absence of smoking at the last follow-up evaluation were associated with long-term clinical success. CONCLUSIONS Endotherapy provides long-term benefits for about two thirds of patients with painful CP. Good clinical outcome was associated with cessation or absence of smoking, whereas alcohol abuse increased the risks for diabetes mellitus, steatorrhea, and mortality.", "author" : [ { "dropping-particle" : "", "family" : "Delhaye", "given" : "Myriam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arvanitakis", "given" : "Marianna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Verset", "given" : "Gontran", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cremer", "given" : "Michel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devi\u00e8re", "given" : "Jacques", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2004", "12" ] ] }, "note" : "NULL", "page" : "1096-106", "title" : "Long-term clinical outcome after endoscopic pancreatic ductal drainage for patients with painful chronic pancreatitis.", "type" : "article-journal", "volume" : "2" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.gie.2012.01.014", "ISSN" : "1097-6779", "PMID" : "22401819", "abstract" : "BACKGROUND Most outcomes data on pancreatic extracorporeal shock wave lithotripsy (P-ESWL) for chronic calcific pancreatitis (CCP) are based on studies with <4 years' follow-up, and U.S. long-term studies are lacking. OBJECTIVE To report long-term P-ESWL outcomes for CCP and to assess whether smoking or alcohol use influences P-ESWL outcomes. DESIGN Cross-sectional study, retrospective chart review. SETTING Virginia Mason Medical Center, Seattle, Washington. PATIENTS This study involved 120 patients who underwent P-ESWL and ERCP for CCP and completed an outcomes questionnaire. INTERVENTION P-ESWL and ERCP, outcomes survey. MAIN OUTCOME MEASUREMENTS Pain, quality of life, narcotics use, diabetes status, pancreatic enzyme requirement, repeat P-ESWL, repeat ERCP, surgery. RESULTS A total of 120 patients underwent P-ESWL followed by ERCP (mean \u00b1 standard deviation [SD] follow-up 4.3 [\u00b1 3.7] years) and completed a survey. The mean (\u00b1 SD) before-P-ESWL pain score was 7.9 (\u00b1 2.6) compared with 2.9 (\u00b1 2.6) after P-ESWL (P < .001). Improved pain was reported by 102 patients (85%); 60 (50%) reported complete pain relief and no narcotic use. The mean (\u00b1 SD) before-P-ESWL quality-of-life score was 3.7 (\u00b1 2.4) compared with 7.3 (\u00b1 2.7) after P-ESWL (P < .001). In patients with \u2265 4 years' follow-up, repeat procedures included P-ESWL (29%), ERCP (84%), and surgery (16%). Smokers who quit smoking after P-ESWL had improved narcotic requirements compared with those who continued smoking (95% vs 67%; P = .014), and a trend suggested a decreased need for repeat ERCPs (68% vs 84%; P = .071). LIMITATIONS Single center, retrospective, recall bias, nonvalidated pain and quality-of-life scales. CONCLUSION P-ESWL as the initial therapy for CCP may lead to more lifetime procedures; however, partial pain relief in 85%, complete pain relief with no narcotic use in 50%, and avoidance of surgery in 84% of patients may be achieved. Quitting smoking after P-ESWL may improve outcomes.", "author" : [ { "dropping-particle" : "", "family" : "Seven", "given" : "Gulseren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schreiner", "given" : "Mitchal A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ross", "given" : "Andrew S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lin", "given" : "Otto S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gluck", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gan", "given" : "S Ian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Irani", "given" : "Shayan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brandabur", "given" : "John J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Patterson", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuhr", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kozarek", "given" : "Richard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastrointestinal endoscopy", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "2012", "5" ] ] }, "note" : "NULL", "page" : "997-1004.e1", "title" : "Long-term outcomes associated with pancreatic extracorporeal shock wave lithotripsy for chronic calcific pancreatitis.", "type" : "article-journal", "volume" : "75" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(255,256)", "plainTextFormattedCitation" : "(255,256)", "previouslyFormattedCitation" : "(255,256)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(255,256). Other prognostic factors for pain relapse during FU were identified in the study by Tadenuma et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1542-3565", "PMID" : "16271345", "abstract" : "BACKGROUND & AIMS The aim of this study was to evaluate the short- and long-term results of extracorporeal shockwave lithotripsy (ESWL) and endoscopic therapy for pancreatic stones. METHODS A total of 117 patients with pancreatic stones underwent ESWL and endoscopic treatment in our institute. Seventy patients who were followed-up for over 3 years after treatment were evaluated retrospectively. RESULTS Immediate pain relief was achieved in 97% and complete removal of stones was achieved in 56%. During the long-term follow-up evaluation, 49 of 70 patients continued to be asymptomatic. Pain recurred more frequently in patients with incomplete removal than in those with complete removal (P < .05). Twenty-one patients who became symptomatic during the follow-up period underwent additional therapy, and pain relief was attained without surgery in all of them. Both endocrine and exocrine function deteriorated after the long-term follow-up period (P < .05). CONCLUSIONS ESWL and endoscopic treatment of pancreatic stones proved to be effective for long-term pain relief, especially in patients in whom stones were removed completely at initial therapy.", "author" : [ { "dropping-particle" : "", "family" : "Tadenuma", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ishihara", "given" : "Takeshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamaguchi", "given" : "Taketo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsuchiya", "given" : "Shouichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kobayashi", "given" : "Akitoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakamura", "given" : "Kazuyoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sakurada", "given" : "Reiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saisho", "given" : "Hiromitsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2005", "11" ] ] }, "note" : "NULL", "page" : "1128-35", "title" : "Long-term results of extracorporeal shockwave lithotripsy and endoscopic therapy for pancreatic stones.", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(234)", "plainTextFormattedCitation" : "(234)", "previouslyFormattedCitation" : "(234)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(234), i.e. incomplete MPD stones removal after ET and the presence of MPD stricture (Table 3).Taking into account all these above data, an algorithm is suggested for selection of good candidates for first-line limited trial of ET ESWL (Figure 3). If clinical success could be obtained with 5 endoscopic interventions, the patient will probably achieve long-term favorable outcome. The cut-off of 5 intervention is based on a study by Ali et al ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1001/archsurg.2012.1094", "ISSN" : "1538-3644", "PMID" : "23117832", "abstract" : "OBJECTIVE To evaluate the effect of timing of surgery on the long-term clinical outcome of surgery in chronic pancreatitis (CP). DESIGN Cohort study with long-term follow-up. SETTING Five specialized academic centers. PATIENTS Patients with CP treated surgically for pain. INTERVENTIONS Pancreatic resection and drainage procedures for pain relief. MAIN OUTCOME MEASURES Pain relief (pain visual analogue score \u22644), pancreatic function, and quality of life. RESULTS We included 266 patients with median follow-up of 62 months (interquartile range, 31-112). Results were presented as odds ratios (ORs)with 95% confidence intervals after correction for bias using bootstrap-corrected analysis. Pain relief was achieved in 149 patients (58%). Surgery within 3 years of symptoms was independently associated with more pain relief (OR, 1.8; 95% CI, 1.0-3.4; P = .03) and less endocrine pancreatic insufficiency (OR, 0.57; 95% CI, 0.33-0.96; P = .04). More pain relief was also observed in patients not taking opioids preoperatively (OR, 2.1; 95% CI, 1.2-4.0; P = .006) and who had 5 or fewer endoscopic treatments prior to surgery (OR, 2.5; 95% CI, 1.1-6.3; P = .04). The probability of achieving pain relief varied between 23% and 75%, depending on these risk factors. CONCLUSIONS The timing of surgery is an important risk factor for clinical outcome in CP. Surgery may need to be considered at an earlier phase than it is now, preferably within 3 years of symptomatic CP. Likelihood of postoperative pain relief can be calculated on an individual basis using the presented nomogram.", "author" : [ { "dropping-particle" : "", "family" : "Ahmed Ali", "given" : "Usama", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nieuwenhuijs", "given" : "Vincent B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eijck", "given" : "Casper H", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gooszen", "given" : "Hein G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dam", "given" : "Ronald M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Busch", "given" : "Olivier R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dijkgraaf", "given" : "Marcel G W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mauritz", "given" : "Femke A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jens", "given" : "Sjoerd", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mast", "given" : "Jay", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goor", "given" : "Harry", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boermeester", "given" : "Marja A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dutch Pancreatitis Study Group", "given" : "for the", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Archives of surgery (Chicago, Ill. : 1960)", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2012", "10", "1" ] ] }, "note" : "NULL", "page" : "925-32", "title" : "Clinical outcome in relation to timing of surgery in chronic pancreatitis: a nomogram to predict pain relief.", "type" : "article-journal", "volume" : "147" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(257)", "plainTextFormattedCitation" : "(257)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(257) They found that more pain relief after surgery was observed in patients who had 5 or fewer endoscopic treatments prior to surgery with an OR of 2.5 (95% CI, 1.1-6.3; p=0.04)). In this study, the multivariable analysis identified 3 independent risk factors for pain relief after surgery. These were pain duration of 3 years or less, no preoperative use of opioids and 5 or less endoscopic procedures prior to surgery. The authors tested also the cut-off of 3 endoscopic treatments with a statistically significant difference in the univariate analysis, but only the cut-off of 5 remained significant in the multivariate analysis. They proposed that the success of endoscopy should be determined in 5 or less endoscopic interventions to optimize outcome of future surgery. If endoscopy does not provide persistent pain relief, then surgery should be considered. Otherwise as observed in 18% of long-term followed patients after ET + ESWLADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1542-3565", "PMID" : "15625655", "abstract" : "BACKGROUND & AIMS Endotherapy for patients with painful chronic pancreatitis (CP) gives early and midterm clinical results comparable with those of conventional surgery. The authors evaluated long-term clinical outcome after endoscopic pancreatic ductal drainage, focusing on pain and pancreatic endocrine/exocrine functions. METHODS Of 110 patients with painful CP endoscopically treated between October 1987 and December 1989, 56 long-surviving patients were followed-up for 14.4 years (SD, .6 y); 40 patients died and 14 patients were lost to follow-up evaluation. Technical results included decreased ductal dilation and stone clearance. Clinical results included the rate of hospitalizations for pain before and after endotherapy, the need for surgery, the course of endocrine/exocrine insufficiencies, and late mortality. RESULTS Complete or partial technical success initially was obtained in 48 of 56 long-surviving patients. Long-term clinical success (< or =5 hospitalizations for pain during follow-up evaluation, without surgery) was obtained for 37 of 56 patients. At a mean follow-up time of 14.4 years, 44 patients had avoided surgery and the annual rate of hospitalizations for pain decreased significantly (before endotherapy: 0.98 [+/-1.36] vs 0.40 [+/-0.51] for the 3 years thereafter vs 0.14 [+/-0.22] for the last 11 years of follow-up evaluation; P < .001). Short duration of disease before initial therapy and absence of smoking at the last follow-up evaluation were associated with long-term clinical success. CONCLUSIONS Endotherapy provides long-term benefits for about two thirds of patients with painful CP. Good clinical outcome was associated with cessation or absence of smoking, whereas alcohol abuse increased the risks for diabetes mellitus, steatorrhea, and mortality.", "author" : [ { "dropping-particle" : "", "family" : "Delhaye", "given" : "Myriam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arvanitakis", "given" : "Marianna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Verset", "given" : "Gontran", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cremer", "given" : "Michel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devi\u00e8re", "given" : "Jacques", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2004", "12" ] ] }, "note" : "NULL", "page" : "1096-106", "title" : "Long-term clinical outcome after endoscopic pancreatic ductal drainage for patients with painful chronic pancreatitis.", "type" : "article-journal", "volume" : "2" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(255)", "plainTextFormattedCitation" : "(255)", "previouslyFormattedCitation" : "(255)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(255), other factors than increased pancreatic ductal pressure could be involved in the pain syndrome and, for these patients, no further attempts at drainage should be proposed.4445000114300-5080Figure 3: The first step for the management of pain in patients with chronic pancreatitis should be to make a correct diagnosis based on clinical history and imaging procedures, and to exclude alternative diseases or complications that could induce pain not related to pancreatic ductal obstruction by stones and/or strictures.The second step should be to select the appropriate candidates for endoscopy (see the text for the definition of best candidates for endoscopical treatment with or without ESWL) and to treat such good candidates early in the disease course (within the first 2 to 3 years after symptom onset), with a limited number (< or = 5) of endoscopic interventions. If no persistent pain relief was obtained after a limited trial of endoscopic treatments +/- ESWL, that means that other factors than increased pancreatic ductal pressure could be involved in the pain syndrome and for these patients no further attempts at drainage should be proposed. In these patients or if the patient is not a candidate for endoscopy or in case of technical failure of endoscopy, medical treatment could be tried. Surgery and alternative options could also be proposed if no persistent pain relief was obtained after endoscopy, in case of limited effect of medical treatment.00Figure 3: The first step for the management of pain in patients with chronic pancreatitis should be to make a correct diagnosis based on clinical history and imaging procedures, and to exclude alternative diseases or complications that could induce pain not related to pancreatic ductal obstruction by stones and/or strictures.The second step should be to select the appropriate candidates for endoscopy (see the text for the definition of best candidates for endoscopical treatment with or without ESWL) and to treat such good candidates early in the disease course (within the first 2 to 3 years after symptom onset), with a limited number (< or = 5) of endoscopic interventions. If no persistent pain relief was obtained after a limited trial of endoscopic treatments +/- ESWL, that means that other factors than increased pancreatic ductal pressure could be involved in the pain syndrome and for these patients no further attempts at drainage should be proposed. In these patients or if the patient is not a candidate for endoscopy or in case of technical failure of endoscopy, medical treatment could be tried. Surgery and alternative options could also be proposed if no persistent pain relief was obtained after endoscopy, in case of limited effect of medical treatment.Christopher Halloran, Myriam Delhaye Q8. Is ESWL effective for pain treatment in CP?In patients with uncomplicated painful calcified CP, ESWL alone is a safe and effective treatment. Best candidates for benefiting from initial first-line ESWL are patients with obstructive calcifications, > 4 mm confined to the head of pancreas. Combining systematic endoscopical therapy with ESWL adds to the cost of patient care, at the same time not probably improving the outcome of pancreatic pain (Quality assessment: moderate, Recommendation strong; Agreement: conditional).ESWL for pancreatic stones is indicated for patients with all of the following:recurrent attacks of pancreatic pain;marked changes in the pancreatic ductal system i.e. dilated main pancreatic ductobstructing ductal stones (minimal diameter: 2 – 5 mm, calcified or radiolucent)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "URL" : "Extracorporeal shock wave lithotripsy for pancreatic stones", "accessed" : { "date-parts" : [ [ "2017", "3", "16" ] ] }, "author" : [ { "dropping-particle" : "", "family" : "M", "given" : "Delhaye", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Up to Date", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "1-9", "title" : "Extracorporeal shock wave lithotripsy for pancreatic stones", "type" : "webpage" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(258)", "plainTextFormattedCitation" : "(258)", "previouslyFormattedCitation" : "(258)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(258)Regardless of the method of shock waves generation (electrohydraulic, electromagnetic, piezoelectric) ESWL provides high rates of stones fragmentation (average of 91% ranging from 54 to 100%)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "URL" : "Extracorporeal shock wave lithotripsy for pancreatic stones", "accessed" : { "date-parts" : [ [ "2017", "3", "16" ] ] }, "author" : [ { "dropping-particle" : "", "family" : "M", "given" : "Delhaye", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Up to Date", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "1-9", "title" : "Extracorporeal shock wave lithotripsy for pancreatic stones", "type" : "webpage" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(258)", "plainTextFormattedCitation" : "(258)", "previouslyFormattedCitation" : "(258)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(258).ESWL was proven useful for treating chronic pancreatitis (CP) related pain in a meta-analysisADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1590-8577", "PMID" : "15650279", "abstract" : "CONTEXT Main pancreatic duct stones may contribute to pain in chronic pancreatitis. Extracorporeal shock wave lithotripsy (ESWL) has been used alone or in combination with endoscopic therapy for fragmentation of stones. Published studies have shown mixed efficacy due to small sample size. OBJECTIVE Systematic analysis of all published data evaluating ESWL with or without endoscopic therapy in pancreatic duct clearance and symptom relief. METHODS Two investigators independently reviewed the computer databases. 31 potential studies were identified. Only studies using ESWL with or without endoscopic therapy were included. Completeness of the search was confirmed by an expert. Studies were independently coded by two investigators and differences rectified by mutual consent. MAIN OUTCOME MEASURES Pain at follow-up and duct clearance. RESULTS Seventeen studies published between 1989 and 2002 were included. Sixteen had a measure of pain at follow-up and duct clearance. All studies were case series with a total of 588 subjects, and included varying number of subjects undergoing endoscopic pancreatic sphincterotomy and stone extraction. The mean effect size (weighted correlation coefficient) for pain was 0.6215 and for duct clearance was 0.7432; thus indicating a large effect. All studies showed homogeneity suggesting similar effect size irrespective of the combinations of therapy. CONCLUSIONS ESWL is effective in clearance of stones from the pancreatic duct and in relief of pain. Published studies showed homogeneity of the effect size of ESWL both in pancreatic duct clearance and relief of pain.", "author" : [ { "dropping-particle" : "", "family" : "Guda", "given" : "Nalini M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Partington", "given" : "Susan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freeman", "given" : "Martin L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "JOP : Journal of the pancreas", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2005", "1", "13" ] ] }, "note" : "NULL", "page" : "6-12", "title" : "Extracorporeal shock wave lithotripsy in the management of chronic calcific pancreatitis: a meta-analysis.", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(259)", "plainTextFormattedCitation" : "(259)", "previouslyFormattedCitation" : "(259)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(259) that included a total of 588 patients from 16 studies. It was concluded from this analysis that ESWL effectively relieves MPD obstruction and alleviates pain in chronic calcifying pancreatitis most often in combination with endoscopic therapy (ET). The mean effect size (weighted correlation coefficient) on pain at follow-up (FU) was 0.62 0.7, with homogeneity reported for effect size between series.A most recent meta-analysis regarding the success of ESWL in chronic calcific pancreatitis management reviewed data from 27 studies including 3189 patientsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/MPA.0000000000000512", "ISSN" : "1536-4828", "PMID" : "26580454", "abstract" : "OBJECTIVES This is a meta-analysis and systematic review to assess the overall utility and safety of Extracorporeal shock wave lithotripsy (ESWL) in chronic calcific pancreatitis. Primary outcomes are pain relief, narcotic usage, ductal clearance, quality of life, and pancreatic exocrine and endocrine function. METHODS Studies involving ESWL in chronic calcific pancreatitis with main pancreatic duct stones greater than 5 mm and patients that failed conservative pain management were included. Fixed and random effects models were used to calculate the pooled proportions. RESULTS Initial search identified 1471 reference articles, in which 184 articles were selected and reviewed. Data were extracted from 27 studies (N = 3189) which met the inclusion criterion. The pooled proportion of patients with absence of pain at follow-up was 52.7% (95% confidence interval [95% CI], 50.85-54.56) and mild to moderate pain at follow-up was 33.43% (95% CI, 31.40-35.50). Quality of life improved in 88.21% (95% CI, 85.43-90.73) and complete ductal clearance was 70.69% (95% CI, 68.97-72.38) in the pooled patients. CONCLUSIONS The ESWL is an effective and safe management option in patients with chronic calcific pancreatitis patients with main pancreatic duct stone size greater than 5 mm who did not get adequate pain relief with conservative management.", "author" : [ { "dropping-particle" : "", "family" : "Moole", "given" : "Harsha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jaeger", "given" : "Amy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bechtold", "given" : "Matthew L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forcione", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Taneja", "given" : "Deepak", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Puli", "given" : "Srinivas R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreas", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2016" ] ] }, "note" : "NULL", "page" : "651-8", "title" : "Success of Extracorporeal Shock Wave Lithotripsy in Chronic Calcific Pancreatitis Management: A Meta-Analysis and Systematic Review.", "type" : "article-journal", "volume" : "45" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(260)", "plainTextFormattedCitation" : "(260)", "previouslyFormattedCitation" : "(260)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(260).The pooled proportion of patients with absence of pain at FU was 53% (95%, CI 51 – 55) and mild to moderate pain at FU was 33% (95%, CI 31 – 36).Narcotic use was decreased in 80% (95% CI, 77 – 82) of the pooled proportion of patients. Surgery was required in 4.4% (95% CI, 4 – 5) of the pooled proportion for various reasons, mainly for inadequate pain control with ESWL. Limitations of this meta-analysis are acknowledged i.e. the varying etiologies of CP, the wide range of FU periods among various studies, the ESWL equipment varied among the studies, the pain score not universal and mainly the absence of control arm in all studies.In a prospective randomized study that compared ESWL alone with ESWL combined with endoscopyADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/gut.2006.096883", "ISSN" : "0017-5749", "PMID" : "17047101", "abstract" : "BACKGROUND In chronic pancreatitis, obstruction of the main pancreatic duct (MPD) may contribute to the pathogenesis of pain. Pilot studies suggest that extracorporeal shock wave lithotripsy (ESWL) alone relieves pain in calcified chronic pancreatitis. AIM To compare ESWL alone with ESWL and endoscopic drainage of the MPD for treatment of pain in chronic pancreatitis. SUBJECTS Patients with uncomplicated painful chronic pancreatitis and calcifications obstructing the MPD. METHODS 55 patients were randomised to ESWL alone (n = 26) or ESWL combined with endoscopy (n = 29). RESULTS 2 years after trial intervention, 10 (38%) and 13 (45%) patients of the ESWL alone and ESWL combined with endoscopy group, respectively, had presented pain relapse (primary outcome) (OR 0.77; 95% CI 0.23 to 2.57). In both groups, a similar decrease was seen after treatment in the MPD diameter (mean decrease 1.7 mm; 95% CI 0.9 to 2.6; p<0.001), and in the number of pain episodes/year (mean decrease, 3.7; 95% CI 2.6 to 4.9; p<0.001). Treatment costs per patient were three times higher in the ESWL combined with endoscopy group compared with the ESWL alone group (p = 0.001). The median delay between the onset of chronic pancreatitis and persistent pain relief for both groups was 1.1 year (95% CI 0.7 to 1.6), as compared with 4 years (95% CI 3 to 4) for the natural history of chronic pancreatitis in a reference cohort (p<0.001). CONCLUSIONS ESWL is a safe and effective preferred treatment for selected patients with painful calcified chronic pancreatitis. Combining systematic endoscopy with ESWL adds to the cost of patient care, without improving the outcome of pancreatic pain.", "author" : [ { "dropping-particle" : "", "family" : "Dumonceau", "given" : "Jean-Marc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Costamagna", "given" : "Guido", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tringali", "given" : "Andrea", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vahedi", "given" : "Kouroche", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delhaye", "given" : "Myriam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hittelet", "given" : "Axel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spera", "given" : "Gianluca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giostra", "given" : "Emiliano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mutignani", "given" : "Massimiliano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maertelaer", "given" : "Viviane", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devi\u00e8re", "given" : "Jacques", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gut", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2007", "4", "1" ] ] }, "note" : "NULL", "page" : "545-52", "title" : "Treatment for painful calcified chronic pancreatitis: extracorporeal shock wave lithotripsy versus endoscopic treatment: a randomised controlled trial.", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(261)", "plainTextFormattedCitation" : "(261)", "previouslyFormattedCitation" : "(261)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(261), including 55 patients with uncomplicated painful CP (no pseudocyst, no bile duct stricture) and calcifications > 4 mm obstructing the MPD, there was no evidence that the combination of endoscopy and ESWL was better than ESWL alone for the prevention of pain.Indeed ESWL alone (n=26) provided similar results than ESWL plus ET (n=29) in terms of decreasing number of pain episodes after trial intervention compared to baseline. Moreover, complete pain relief, 2 years after treatment, was achieved in 62% and 55%, respectively (p=NS).ESWL alone was also reported as a first-line treatment of calcified pancreatic stones in three non-randomized Japanese studiesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0002-9270", "PMID" : "8678001", "abstract" : "OBJECTIVES We performed extracorporeal shock wave lithotripsy (ESWL) as the treatment of first choice on 32 chronic pancreatitis patients with main pancreatic duct (MPD) stones prospectively to establish more convenient and safer treatment. METHODS All patients were treated in a prone position, and shock waves were discharged from the ventral side. ESWL was performed once or twice a week, and no other treatments before ESWL had been applied. RESULTS Disintegration of all MPD stones to 3 mm or less in diameter could be achieved in all treated patients. Complete clearance of the stones was obtained in 24 patients (75%) without the necessity of endoscopic extraction of fragments. Reduction of MPD diameters after ESWL was statistically significant (p < 0.01). Epigastric and/or back pain complaints before ESWL were completely alleviated in 79% (periods of follow-up: 16-63 months, mean 44), and the pancreatic exocrine function also improved in 61%. No severe complications occurred in any of the patients. CONCLUSIONS ESWL, which is comparatively easy to perform, is a safe and efficient approach that changes endoscopy's status as an indispensable pretreatment. Therefore, ESWL can be recommended as the first choice treatment for patients with chronic pancreatitis accompanied by MPD stones that should be tried before consideration of either surgical or endoscopic procedures.", "author" : [ { "dropping-particle" : "", "family" : "Ohara", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoshino", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayakawa", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kamiya", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyaji", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takeuchi", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okayama", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gotoh", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American journal of gastroenterology", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "1996", "7" ] ] }, "note" : "NULL", "page" : "1388-94", "title" : "Single application extracorporeal shock wave lithotripsy is the first choice for patients with pancreatic duct stones.", "type" : "article-journal", "volume" : "91" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "1536-4828", "PMID" : "15632696", "abstract" : "OBJECTIVES A retrospective multicenter survey was performed to evaluate the efficacy of extracorporeal shock wave lithotripsy (ESWL) as a treatment of pancreatic stones. METHODS A survey was sent to 11 institutions belonging to the Japanese Association of Extracorporeal Shock Wave Lithotripsy in Digestive Diseases, and data were collected on 555 patients who underwent ESWL for pancreatic stones between January 1990 and September 2002. The male:female ratio was 5.2:1, and the mean age was 52.5 years. The etiology was alcohol related in 425 patients (76.6%) and idiopathic in 111 patients (20.0%); 204 patients (36.8%) had a single stone and 470 patients (84.7%) were symptomatic. RESULTS Mean frequency of the procedure was 5.0 times (range, 1-29). Fragmentation of stones was achieved in 513 patients (92.4%), and the complete stone clearance rate after ESWL alone or in combination with interventional endoscopy was 72.6%. Symptom relief was achieved in 428 (91.1%) of 470 patients. Thirty-five patients (6.3%) developed complications, including 30 patients (5.4%) who developed acute pancreatitis. Five hundred four (90.8%) patients were followed for a mean of 44.3 months, during which 122 (22.0%) suffered stone recurrence (mean time to recurrence, 25.1 months). Twenty-two (4.1%) of the 504 patients who were followed required surgery. Pancreatic exocrine function improved in 65 patients (38.0%), was unchanged in 49 patients (28.7%), and progressed in 57 patients (33.3%). Pancreatic endocrine function improved in 44 patients (24.3%), was unchanged in 85 patients (47.0%), and progressed in 52 patients (28.7%). CONCLUSION ESWL is the treatment of choice for clearing pancreatic stones.", "author" : [ { "dropping-particle" : "", "family" : "Inui", "given" : "Kazuo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tazuma", "given" : "Susumu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamaguchi", "given" : "Taketo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ohara", "given" : "Hirotaka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsuji", "given" : "Tadao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyagawa", "given" : "Hiroyuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Igarashi", "given" : "Yoshinori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakamura", "given" : "Yuta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atomi", "given" : "Yutaka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreas", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2005", "1" ] ] }, "note" : "NULL", "page" : "26-30", "title" : "Treatment of pancreatic stones with extracorporeal shock wave lithotripsy: results of a multicenter survey.", "type" : "article-journal", "volume" : "30" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1097/MPA.0b013e31827308c8", "ISSN" : "1536-4828", "PMID" : "23558239", "abstract" : "OBJECTIVES A Japanese multicenter study of pancreatolithiasis was performed to investigate its clinical features and determine treatment strategies for pancreatolithiasis. METHODS A retrospective study was performed on 916 patients managed in 34 institutions for a period of more than 5 years. RESULTS The treatment methods were extracorporeal shock wave lithotripsy (ESWL) in 479 patients, surgery in 133, and endoscopy alone in 68. Fragmentation of stones after ESWL was achieved in 92.4% of the patients. However, complete stone clearance was achieved in 49.4% of the patients after ESWL alone. The complete stone clearance rate was lower after ESWL than after endoscopy (87.9%). The incidence of early complications was significantly higher after surgery (13.3%) than after ESWL (6.1%). The frequencies of total stone recurrence after ESWL (22.5%) and endoscopy (12.0%) were significantly higher than that after surgery (1.5%). After ESWL (17.6%), abdominal pain recurred significantly more frequently than after surgery (2.2%). Stones and abdominal pain most often recurred within 3 years after ESWL and endoscopy. CONCLUSIONS First-line treatment of pancreatic stones should be ESWL alone or with endoscopy because of its minimal invasiveness and low incidence of early complications. Surgery should be performed on patients in whom ESWL and endoscopy failed.", "author" : [ { "dropping-particle" : "", "family" : "Suzuki", "given" : "Yutaka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sugiyama", "given" : "Masanori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Inui", "given" : "Kazuo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Igarashi", "given" : "Yoshinori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ohara", "given" : "Hirotaka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tazuma", "given" : "Susumu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsuji", "given" : "Tadao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyakawa", "given" : "Hiroyuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atomi", "given" : "Yutaka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreas", "id" : "ITEM-3", "issue" : "4", "issued" : { "date-parts" : [ [ "2013", "5" ] ] }, "note" : "NULL", "page" : "584-8", "title" : "Management for pancreatolithiasis: a Japanese multicenter study.", "type" : "article-journal", "volume" : "42" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(262\u2013264)", "plainTextFormattedCitation" : "(262\u2013264)", "previouslyFormattedCitation" : "(262\u2013264)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(262–264) (Table 6). Interestingly, the proportion of patients treated by ESWL alone in one large study was 57% (318 / 555)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1536-4828", "PMID" : "15632696", "abstract" : "OBJECTIVES A retrospective multicenter survey was performed to evaluate the efficacy of extracorporeal shock wave lithotripsy (ESWL) as a treatment of pancreatic stones. METHODS A survey was sent to 11 institutions belonging to the Japanese Association of Extracorporeal Shock Wave Lithotripsy in Digestive Diseases, and data were collected on 555 patients who underwent ESWL for pancreatic stones between January 1990 and September 2002. The male:female ratio was 5.2:1, and the mean age was 52.5 years. The etiology was alcohol related in 425 patients (76.6%) and idiopathic in 111 patients (20.0%); 204 patients (36.8%) had a single stone and 470 patients (84.7%) were symptomatic. RESULTS Mean frequency of the procedure was 5.0 times (range, 1-29). Fragmentation of stones was achieved in 513 patients (92.4%), and the complete stone clearance rate after ESWL alone or in combination with interventional endoscopy was 72.6%. Symptom relief was achieved in 428 (91.1%) of 470 patients. Thirty-five patients (6.3%) developed complications, including 30 patients (5.4%) who developed acute pancreatitis. Five hundred four (90.8%) patients were followed for a mean of 44.3 months, during which 122 (22.0%) suffered stone recurrence (mean time to recurrence, 25.1 months). Twenty-two (4.1%) of the 504 patients who were followed required surgery. Pancreatic exocrine function improved in 65 patients (38.0%), was unchanged in 49 patients (28.7%), and progressed in 57 patients (33.3%). Pancreatic endocrine function improved in 44 patients (24.3%), was unchanged in 85 patients (47.0%), and progressed in 52 patients (28.7%). CONCLUSION ESWL is the treatment of choice for clearing pancreatic stones.", "author" : [ { "dropping-particle" : "", "family" : "Inui", "given" : "Kazuo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tazuma", "given" : "Susumu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamaguchi", "given" : "Taketo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ohara", "given" : "Hirotaka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsuji", "given" : "Tadao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyagawa", "given" : "Hiroyuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Igarashi", "given" : "Yoshinori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakamura", "given" : "Yuta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atomi", "given" : "Yutaka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreas", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2005", "1" ] ] }, "note" : "NULL", "page" : "26-30", "title" : "Treatment of pancreatic stones with extracorporeal shock wave lithotripsy: results of a multicenter survey.", "type" : "article-journal", "volume" : "30" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(263)", "plainTextFormattedCitation" : "(263)", "previouslyFormattedCitation" : "(263)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(263).Among 552 patients who underwent ESWL alone and included in these three studies, complete spontaneous MPD clearance was obtained in 63% (345 / 552, range 49% - 75%). In the study by Inui et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1536-4828", "PMID" : "15632696", "abstract" : "OBJECTIVES A retrospective multicenter survey was performed to evaluate the efficacy of extracorporeal shock wave lithotripsy (ESWL) as a treatment of pancreatic stones. METHODS A survey was sent to 11 institutions belonging to the Japanese Association of Extracorporeal Shock Wave Lithotripsy in Digestive Diseases, and data were collected on 555 patients who underwent ESWL for pancreatic stones between January 1990 and September 2002. The male:female ratio was 5.2:1, and the mean age was 52.5 years. The etiology was alcohol related in 425 patients (76.6%) and idiopathic in 111 patients (20.0%); 204 patients (36.8%) had a single stone and 470 patients (84.7%) were symptomatic. RESULTS Mean frequency of the procedure was 5.0 times (range, 1-29). Fragmentation of stones was achieved in 513 patients (92.4%), and the complete stone clearance rate after ESWL alone or in combination with interventional endoscopy was 72.6%. Symptom relief was achieved in 428 (91.1%) of 470 patients. Thirty-five patients (6.3%) developed complications, including 30 patients (5.4%) who developed acute pancreatitis. Five hundred four (90.8%) patients were followed for a mean of 44.3 months, during which 122 (22.0%) suffered stone recurrence (mean time to recurrence, 25.1 months). Twenty-two (4.1%) of the 504 patients who were followed required surgery. Pancreatic exocrine function improved in 65 patients (38.0%), was unchanged in 49 patients (28.7%), and progressed in 57 patients (33.3%). Pancreatic endocrine function improved in 44 patients (24.3%), was unchanged in 85 patients (47.0%), and progressed in 52 patients (28.7%). CONCLUSION ESWL is the treatment of choice for clearing pancreatic stones.", "author" : [ { "dropping-particle" : "", "family" : "Inui", "given" : "Kazuo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tazuma", "given" : "Susumu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamaguchi", "given" : "Taketo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ohara", "given" : "Hirotaka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsuji", "given" : "Tadao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyagawa", "given" : "Hiroyuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Igarashi", "given" : "Yoshinori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakamura", "given" : "Yuta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atomi", "given" : "Yutaka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreas", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2005", "1" ] ] }, "note" : "NULL", "page" : "26-30", "title" : "Treatment of pancreatic stones with extracorporeal shock wave lithotripsy: results of a multicenter survey.", "type" : "article-journal", "volume" : "30" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(263)", "plainTextFormattedCitation" : "(263)", "previouslyFormattedCitation" : "(263)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(263) the spontaneous ductal clearance after ESWL alone was not significantly different from that observed in the whole series (70% vs 73%). On the other hand, the ductal clearance rates were 49% after ESWL alone and 74% after ESWL ET in the study by Suzuki et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/MPA.0b013e31827308c8", "ISSN" : "1536-4828", "PMID" : "23558239", "abstract" : "OBJECTIVES A Japanese multicenter study of pancreatolithiasis was performed to investigate its clinical features and determine treatment strategies for pancreatolithiasis. METHODS A retrospective study was performed on 916 patients managed in 34 institutions for a period of more than 5 years. RESULTS The treatment methods were extracorporeal shock wave lithotripsy (ESWL) in 479 patients, surgery in 133, and endoscopy alone in 68. Fragmentation of stones after ESWL was achieved in 92.4% of the patients. However, complete stone clearance was achieved in 49.4% of the patients after ESWL alone. The complete stone clearance rate was lower after ESWL than after endoscopy (87.9%). The incidence of early complications was significantly higher after surgery (13.3%) than after ESWL (6.1%). The frequencies of total stone recurrence after ESWL (22.5%) and endoscopy (12.0%) were significantly higher than that after surgery (1.5%). After ESWL (17.6%), abdominal pain recurred significantly more frequently than after surgery (2.2%). Stones and abdominal pain most often recurred within 3 years after ESWL and endoscopy. CONCLUSIONS First-line treatment of pancreatic stones should be ESWL alone or with endoscopy because of its minimal invasiveness and low incidence of early complications. Surgery should be performed on patients in whom ESWL and endoscopy failed.", "author" : [ { "dropping-particle" : "", "family" : "Suzuki", "given" : "Yutaka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sugiyama", "given" : "Masanori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Inui", "given" : "Kazuo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Igarashi", "given" : "Yoshinori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ohara", "given" : "Hirotaka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tazuma", "given" : "Susumu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsuji", "given" : "Tadao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyakawa", "given" : "Hiroyuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atomi", "given" : "Yutaka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreas", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2013", "5" ] ] }, "note" : "NULL", "page" : "584-8", "title" : "Management for pancreatolithiasis: a Japanese multicenter study.", "type" : "article-journal", "volume" : "42" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(264)", "plainTextFormattedCitation" : "(264)", "previouslyFormattedCitation" : "(264)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(264).Factors associated with complete stone clearance included the presence of a single stone vs. multiple stonesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1542-3565", "PMID" : "16271345", "abstract" : "BACKGROUND & AIMS The aim of this study was to evaluate the short- and long-term results of extracorporeal shockwave lithotripsy (ESWL) and endoscopic therapy for pancreatic stones. METHODS A total of 117 patients with pancreatic stones underwent ESWL and endoscopic treatment in our institute. Seventy patients who were followed-up for over 3 years after treatment were evaluated retrospectively. RESULTS Immediate pain relief was achieved in 97% and complete removal of stones was achieved in 56%. During the long-term follow-up evaluation, 49 of 70 patients continued to be asymptomatic. Pain recurred more frequently in patients with incomplete removal than in those with complete removal (P < .05). Twenty-one patients who became symptomatic during the follow-up period underwent additional therapy, and pain relief was attained without surgery in all of them. Both endocrine and exocrine function deteriorated after the long-term follow-up period (P < .05). CONCLUSIONS ESWL and endoscopic treatment of pancreatic stones proved to be effective for long-term pain relief, especially in patients in whom stones were removed completely at initial therapy.", "author" : [ { "dropping-particle" : "", "family" : "Tadenuma", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ishihara", "given" : "Takeshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamaguchi", "given" : "Taketo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsuchiya", "given" : "Shouichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kobayashi", "given" : "Akitoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakamura", "given" : "Kazuyoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sakurada", "given" : "Reiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saisho", "given" : "Hiromitsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2005", "11" ] ] }, "note" : "NULL", "page" : "1128-35", "title" : "Long-term results of extracorporeal shockwave lithotripsy and endoscopic therapy for pancreatic stones.", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0017-5749", "PMID" : "10446109", "abstract" : "BACKGROUND There have been conflicting reports as to whether pancreatic ductal drainage achieved by endoscopy and lithotripsy improves the clinical outcome of patients with chronic pancreatitis. AIMS To determine the clinical outcome in patients with chronic pancreatitis who received extracorporeal shock wave lithotripsy (ESWL), and were followed up for two to eight years. METHODS Eighty patients with severe chronic pancreatitis and endoscopically unretrievable obstructive stones underwent ESWL with a piezoelectric lithotripter between 1989 and 1996. Clinical status, relief of symptoms, further endoscopic or surgical interventions, and mortality were defined. RESULTS Forty three (54%) patients were treated successfully with ESWL. The only feature associated with treatment success was the presence of a single stone rather than multiple stones. Successfully treated patients tended to experience less pain, although this did not reach statistical significance. A slight increase in weight was noted in our patients; however, there was no notable improvement in anomalous stools and diabetes mellitus. Five patients died due to extrapancreatic reasons. No pancreatic carcinomas developed. CONCLUSIONS ESWL associated with endoscopic drainage is a safe technique that is particularly successful in patients with a single stone. However, pancreatic drainage by endoscopy and ESWL has almost no effect on pain in chronic pancreatitis. Furthermore, endoscopic management and ESWL does not prevent or postpone the development of glandular insufficiency.", "author" : [ { "dropping-particle" : "", "family" : "Adamek", "given" : "H E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jakobs", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buttmann", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adamek", "given" : "M U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schneider", "given" : "A R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Riemann", "given" : "J F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gut", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "1999", "9" ] ] }, "note" : "NULL", "page" : "402-5", "title" : "Long term follow up of patients with chronic pancreatitis and pancreatic stones treated with extracorporeal shock wave lithotripsy.", "type" : "article-journal", "volume" : "45" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(234,265)", "plainTextFormattedCitation" : "(234,265)", "previouslyFormattedCitation" : "(234,265)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(234,265) the absence of a MPD strictureADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1542-3565", "PMID" : "16271345", "abstract" : "BACKGROUND & AIMS The aim of this study was to evaluate the short- and long-term results of extracorporeal shockwave lithotripsy (ESWL) and endoscopic therapy for pancreatic stones. METHODS A total of 117 patients with pancreatic stones underwent ESWL and endoscopic treatment in our institute. Seventy patients who were followed-up for over 3 years after treatment were evaluated retrospectively. RESULTS Immediate pain relief was achieved in 97% and complete removal of stones was achieved in 56%. During the long-term follow-up evaluation, 49 of 70 patients continued to be asymptomatic. Pain recurred more frequently in patients with incomplete removal than in those with complete removal (P < .05). Twenty-one patients who became symptomatic during the follow-up period underwent additional therapy, and pain relief was attained without surgery in all of them. Both endocrine and exocrine function deteriorated after the long-term follow-up period (P < .05). CONCLUSIONS ESWL and endoscopic treatment of pancreatic stones proved to be effective for long-term pain relief, especially in patients in whom stones were removed completely at initial therapy.", "author" : [ { "dropping-particle" : "", "family" : "Tadenuma", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ishihara", "given" : "Takeshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamaguchi", "given" : "Taketo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsuchiya", "given" : "Shouichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kobayashi", "given" : "Akitoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakamura", "given" : "Kazuyoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sakurada", "given" : "Reiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saisho", "given" : "Hiromitsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2005", "11" ] ] }, "note" : "NULL", "page" : "1128-35", "title" : "Long-term results of extracorporeal shockwave lithotripsy and endoscopic therapy for pancreatic stones.", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(234)", "plainTextFormattedCitation" : "(234)", "previouslyFormattedCitation" : "(234)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(234) and a lower density of stones (< 820 Hounsfield units)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/MPA.0000000000000277", "ISSN" : "1536-4828", "PMID" : "25438070", "abstract" : "OBJECTIVES Patients with chronic pancreatitis are managed by extracorporeal shock wave lithotripsy (ESWL) for pancreatic stones. Stone density on noncontrast computed tomography (NCCT) is used to predict stone composition and fragility, but no report investigating the pancreatic stone density has been documented. We aimed to assess the usefulness of pancreatic stone density on NCCT in predicting the ESWL outcome. METHODS We evaluated 128 consecutive patients with pancreatic stones who underwent ESWL. Pancreatic stone density on NCCT was measured in Hounsfield units. Patients with complete stone removal were compared with those with incomplete stone removal. Patient characteristics; imaging findings, including stone density; and interventions were evaluated as potential predictors. The optimal cutoff value of variables to differentiate complete removal from incomplete removal was determined by receiver operating characteristic analysis. RESULTS Complete stone removal was achieved in 66 patients (51.6%). When the density threshold was set at 820.5 Hounsfield units, complete stone removal was achieved in 52 patients (78.8%) with lower-density stones. In multivariate analysis, single stone (P = 0.007) and lower-density stone (P < 0.001) revealed significant association with complete stone removal. CONCLUSIONS The measurement of pancreatic stone density before therapy can help predict therapeutic outcomes.", "author" : [ { "dropping-particle" : "", "family" : "Ohyama", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mikata", "given" : "Rintaro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ishihara", "given" : "Takeshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsuyuguchi", "given" : "Toshio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sakai", "given" : "Yuji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sugiyama", "given" : "Harutoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yasui", "given" : "Shin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ishii", "given" : "Kiyofumi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Itoh", "given" : "Sadahiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nishikawa", "given" : "Takao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Yuto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yokosuka", "given" : "Osamu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreas", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2015", "4" ] ] }, "note" : "NULL", "page" : "422-8", "title" : "Efficacy of stone density on noncontrast computed tomography in predicting the outcome of extracorporeal shock wave lithotripsy for patients with pancreatic stones.", "type" : "article-journal", "volume" : "44" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(266)", "plainTextFormattedCitation" : "(266)", "previouslyFormattedCitation" : "(266)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(266).In the study by Ohara et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0002-9270", "PMID" : "8678001", "abstract" : "OBJECTIVES We performed extracorporeal shock wave lithotripsy (ESWL) as the treatment of first choice on 32 chronic pancreatitis patients with main pancreatic duct (MPD) stones prospectively to establish more convenient and safer treatment. METHODS All patients were treated in a prone position, and shock waves were discharged from the ventral side. ESWL was performed once or twice a week, and no other treatments before ESWL had been applied. RESULTS Disintegration of all MPD stones to 3 mm or less in diameter could be achieved in all treated patients. Complete clearance of the stones was obtained in 24 patients (75%) without the necessity of endoscopic extraction of fragments. Reduction of MPD diameters after ESWL was statistically significant (p < 0.01). Epigastric and/or back pain complaints before ESWL were completely alleviated in 79% (periods of follow-up: 16-63 months, mean 44), and the pancreatic exocrine function also improved in 61%. No severe complications occurred in any of the patients. CONCLUSIONS ESWL, which is comparatively easy to perform, is a safe and efficient approach that changes endoscopy's status as an indispensable pretreatment. Therefore, ESWL can be recommended as the first choice treatment for patients with chronic pancreatitis accompanied by MPD stones that should be tried before consideration of either surgical or endoscopic procedures.", "author" : [ { "dropping-particle" : "", "family" : "Ohara", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoshino", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayakawa", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kamiya", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyaji", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takeuchi", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okayama", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gotoh", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American journal of gastroenterology", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "1996", "7" ] ] }, "note" : "NULL", "page" : "1388-94", "title" : "Single application extracorporeal shock wave lithotripsy is the first choice for patients with pancreatic duct stones.", "type" : "article-journal", "volume" : "91" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(262)", "plainTextFormattedCitation" : "(262)", "previouslyFormattedCitation" : "(262)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(262), a high rate of complete or partial pain relief (24/32, 75%) was obtained after ESWL alone over a mean FU of 44 months. This could be explained by the selection of patients without severe MPD stricture (in 22 out of 32 patients) and with good residual exocrine pancreatic function (only 2 patients (6%) presented steatorrhea) in this study.After treatment with ESWL (alone or combined with endoscopic drainage), most of the patients who experienced pain relapses developed them during the first two years following treatmentADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0016-5107", "PMID" : "8781931", "abstract" : "BACKGROUND In severe chronic pancreatitis associated with intraductal stones, therapeutic endoscopy aims to reduce increased intraductal pressure by pancreatic sphincterotomy and stone clearance. METHODS Results of treatment were evaluated in 70 new patients who underwent pancreatic sphincterotomy and attempted stone removal. Technical results and frequency of pain relief and recurrence are compared. RESULTS Complete ductal clearance of calculi was obtained in 50% of cases. Immediate clinical improvement occurred in 95% of patients with painful attacks. No severe complications or mortality occurred. Fifty-four percent of all patients with painful chronic pancreatitis did not experience any pain recurrence within 2 years. Associations found to be statistically significant by multivariate analysis were ductal clearance and extracorporeal shock wave lithotripsy, pain disappearance and ductal clearance, pain recurrence and long evolution, and severe disease before treatment and presence of a ductal substenosis. CONCLUSIONS In this subset of patients our results indicate that the pain of chronic pancreatitis is mainly related to increased intraductal pressure. Endoscopic management appears to be a safe, conservative, alternative to surgery. The best results are obtained when it is performed early in the course of calcifying chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Dumonceau", "given" : "J M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devi\u00e8re", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moine", "given" : "O", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delhaye", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vandermeeren", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baize", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gansbeke", "given" : "D", "non-dropping-particle" : "Van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cremer", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastrointestinal endoscopy", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "1996", "6" ] ] }, "note" : "NULL", "page" : "547-55", "title" : "Endoscopic pancreatic drainage in chronic pancreatitis associated with ductal stones: long-term results.", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "1542-3565", "PMID" : "15625655", "abstract" : "BACKGROUND & AIMS Endotherapy for patients with painful chronic pancreatitis (CP) gives early and midterm clinical results comparable with those of conventional surgery. The authors evaluated long-term clinical outcome after endoscopic pancreatic ductal drainage, focusing on pain and pancreatic endocrine/exocrine functions. METHODS Of 110 patients with painful CP endoscopically treated between October 1987 and December 1989, 56 long-surviving patients were followed-up for 14.4 years (SD, .6 y); 40 patients died and 14 patients were lost to follow-up evaluation. Technical results included decreased ductal dilation and stone clearance. Clinical results included the rate of hospitalizations for pain before and after endotherapy, the need for surgery, the course of endocrine/exocrine insufficiencies, and late mortality. RESULTS Complete or partial technical success initially was obtained in 48 of 56 long-surviving patients. Long-term clinical success (< or =5 hospitalizations for pain during follow-up evaluation, without surgery) was obtained for 37 of 56 patients. At a mean follow-up time of 14.4 years, 44 patients had avoided surgery and the annual rate of hospitalizations for pain decreased significantly (before endotherapy: 0.98 [+/-1.36] vs 0.40 [+/-0.51] for the 3 years thereafter vs 0.14 [+/-0.22] for the last 11 years of follow-up evaluation; P < .001). Short duration of disease before initial therapy and absence of smoking at the last follow-up evaluation were associated with long-term clinical success. CONCLUSIONS Endotherapy provides long-term benefits for about two thirds of patients with painful CP. Good clinical outcome was associated with cessation or absence of smoking, whereas alcohol abuse increased the risks for diabetes mellitus, steatorrhea, and mortality.", "author" : [ { "dropping-particle" : "", "family" : "Delhaye", "given" : "Myriam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arvanitakis", "given" : "Marianna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Verset", "given" : "Gontran", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cremer", "given" : "Michel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devi\u00e8re", "given" : "Jacques", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association", "id" : "ITEM-2", "issue" : "12", "issued" : { "date-parts" : [ [ "2004", "12" ] ] }, "note" : "NULL", "page" : "1096-106", "title" : "Long-term clinical outcome after endoscopic pancreatic ductal drainage for patients with painful chronic pancreatitis.", "type" : "article-journal", "volume" : "2" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1136/gut.2006.096883", "ISSN" : "0017-5749", "PMID" : "17047101", "abstract" : "BACKGROUND In chronic pancreatitis, obstruction of the main pancreatic duct (MPD) may contribute to the pathogenesis of pain. Pilot studies suggest that extracorporeal shock wave lithotripsy (ESWL) alone relieves pain in calcified chronic pancreatitis. AIM To compare ESWL alone with ESWL and endoscopic drainage of the MPD for treatment of pain in chronic pancreatitis. SUBJECTS Patients with uncomplicated painful chronic pancreatitis and calcifications obstructing the MPD. METHODS 55 patients were randomised to ESWL alone (n = 26) or ESWL combined with endoscopy (n = 29). RESULTS 2 years after trial intervention, 10 (38%) and 13 (45%) patients of the ESWL alone and ESWL combined with endoscopy group, respectively, had presented pain relapse (primary outcome) (OR 0.77; 95% CI 0.23 to 2.57). In both groups, a similar decrease was seen after treatment in the MPD diameter (mean decrease 1.7 mm; 95% CI 0.9 to 2.6; p<0.001), and in the number of pain episodes/year (mean decrease, 3.7; 95% CI 2.6 to 4.9; p<0.001). Treatment costs per patient were three times higher in the ESWL combined with endoscopy group compared with the ESWL alone group (p = 0.001). The median delay between the onset of chronic pancreatitis and persistent pain relief for both groups was 1.1 year (95% CI 0.7 to 1.6), as compared with 4 years (95% CI 3 to 4) for the natural history of chronic pancreatitis in a reference cohort (p<0.001). CONCLUSIONS ESWL is a safe and effective preferred treatment for selected patients with painful calcified chronic pancreatitis. Combining systematic endoscopy with ESWL adds to the cost of patient care, without improving the outcome of pancreatic pain.", "author" : [ { "dropping-particle" : "", "family" : "Dumonceau", "given" : "Jean-Marc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Costamagna", "given" : "Guido", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tringali", "given" : "Andrea", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vahedi", "given" : "Kouroche", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delhaye", "given" : "Myriam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hittelet", "given" : "Axel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spera", "given" : "Gianluca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giostra", "given" : "Emiliano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mutignani", "given" : "Massimiliano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maertelaer", "given" : "Viviane", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devi\u00e8re", "given" : "Jacques", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gut", "id" : "ITEM-3", "issue" : "4", "issued" : { "date-parts" : [ [ "2007", "4", "1" ] ] }, "note" : "NULL", "page" : "545-52", "title" : "Treatment for painful calcified chronic pancreatitis: extracorporeal shock wave lithotripsy versus endoscopic treatment: a randomised controlled trial.", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(251,255,261)", "plainTextFormattedCitation" : "(251,255,261)", "previouslyFormattedCitation" : "(251,255,261)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(251,255,261). Interestingly, after treatment with ESWL alone, need for ERCP for pain relapses has been reported in only 3/32 (9%)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0002-9270", "PMID" : "8678001", "abstract" : "OBJECTIVES We performed extracorporeal shock wave lithotripsy (ESWL) as the treatment of first choice on 32 chronic pancreatitis patients with main pancreatic duct (MPD) stones prospectively to establish more convenient and safer treatment. METHODS All patients were treated in a prone position, and shock waves were discharged from the ventral side. ESWL was performed once or twice a week, and no other treatments before ESWL had been applied. RESULTS Disintegration of all MPD stones to 3 mm or less in diameter could be achieved in all treated patients. Complete clearance of the stones was obtained in 24 patients (75%) without the necessity of endoscopic extraction of fragments. Reduction of MPD diameters after ESWL was statistically significant (p < 0.01). Epigastric and/or back pain complaints before ESWL were completely alleviated in 79% (periods of follow-up: 16-63 months, mean 44), and the pancreatic exocrine function also improved in 61%. No severe complications occurred in any of the patients. CONCLUSIONS ESWL, which is comparatively easy to perform, is a safe and efficient approach that changes endoscopy's status as an indispensable pretreatment. Therefore, ESWL can be recommended as the first choice treatment for patients with chronic pancreatitis accompanied by MPD stones that should be tried before consideration of either surgical or endoscopic procedures.", "author" : [ { "dropping-particle" : "", "family" : "Ohara", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoshino", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayakawa", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kamiya", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyaji", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takeuchi", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okayama", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gotoh", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American journal of gastroenterology", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "1996", "7" ] ] }, "note" : "NULL", "page" : "1388-94", "title" : "Single application extracorporeal shock wave lithotripsy is the first choice for patients with pancreatic duct stones.", "type" : "article-journal", "volume" : "91" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(262)", "plainTextFormattedCitation" : "(262)", "previouslyFormattedCitation" : "(262)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(262) and in 8/26 (31%)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/gut.2006.096883", "ISSN" : "0017-5749", "PMID" : "17047101", "abstract" : "BACKGROUND In chronic pancreatitis, obstruction of the main pancreatic duct (MPD) may contribute to the pathogenesis of pain. Pilot studies suggest that extracorporeal shock wave lithotripsy (ESWL) alone relieves pain in calcified chronic pancreatitis. AIM To compare ESWL alone with ESWL and endoscopic drainage of the MPD for treatment of pain in chronic pancreatitis. SUBJECTS Patients with uncomplicated painful chronic pancreatitis and calcifications obstructing the MPD. METHODS 55 patients were randomised to ESWL alone (n = 26) or ESWL combined with endoscopy (n = 29). RESULTS 2 years after trial intervention, 10 (38%) and 13 (45%) patients of the ESWL alone and ESWL combined with endoscopy group, respectively, had presented pain relapse (primary outcome) (OR 0.77; 95% CI 0.23 to 2.57). In both groups, a similar decrease was seen after treatment in the MPD diameter (mean decrease 1.7 mm; 95% CI 0.9 to 2.6; p<0.001), and in the number of pain episodes/year (mean decrease, 3.7; 95% CI 2.6 to 4.9; p<0.001). Treatment costs per patient were three times higher in the ESWL combined with endoscopy group compared with the ESWL alone group (p = 0.001). The median delay between the onset of chronic pancreatitis and persistent pain relief for both groups was 1.1 year (95% CI 0.7 to 1.6), as compared with 4 years (95% CI 3 to 4) for the natural history of chronic pancreatitis in a reference cohort (p<0.001). CONCLUSIONS ESWL is a safe and effective preferred treatment for selected patients with painful calcified chronic pancreatitis. Combining systematic endoscopy with ESWL adds to the cost of patient care, without improving the outcome of pancreatic pain.", "author" : [ { "dropping-particle" : "", "family" : "Dumonceau", "given" : "Jean-Marc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Costamagna", "given" : "Guido", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tringali", "given" : "Andrea", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vahedi", "given" : "Kouroche", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delhaye", "given" : "Myriam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hittelet", "given" : "Axel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spera", "given" : "Gianluca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giostra", "given" : "Emiliano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mutignani", "given" : "Massimiliano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maertelaer", "given" : "Viviane", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devi\u00e8re", "given" : "Jacques", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gut", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2007", "4", "1" ] ] }, "note" : "NULL", "page" : "545-52", "title" : "Treatment for painful calcified chronic pancreatitis: extracorporeal shock wave lithotripsy versus endoscopic treatment: a randomised controlled trial.", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(261)", "plainTextFormattedCitation" : "(261)", "previouslyFormattedCitation" : "(261)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(261) patients during FU.Pain relapse occurred significantly more frequently in patients with incomplete removal of stones after the initial therapy (ET ESWL) (HR, 3.7; p=0.007) and in those with a MPD stricture (HR, 3.4, p=0.02). Both factors were significant risk factors for pain relapse on multivariate analysisADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1542-3565", "PMID" : "16271345", "abstract" : "BACKGROUND & AIMS The aim of this study was to evaluate the short- and long-term results of extracorporeal shockwave lithotripsy (ESWL) and endoscopic therapy for pancreatic stones. METHODS A total of 117 patients with pancreatic stones underwent ESWL and endoscopic treatment in our institute. Seventy patients who were followed-up for over 3 years after treatment were evaluated retrospectively. RESULTS Immediate pain relief was achieved in 97% and complete removal of stones was achieved in 56%. During the long-term follow-up evaluation, 49 of 70 patients continued to be asymptomatic. Pain recurred more frequently in patients with incomplete removal than in those with complete removal (P < .05). Twenty-one patients who became symptomatic during the follow-up period underwent additional therapy, and pain relief was attained without surgery in all of them. Both endocrine and exocrine function deteriorated after the long-term follow-up period (P < .05). CONCLUSIONS ESWL and endoscopic treatment of pancreatic stones proved to be effective for long-term pain relief, especially in patients in whom stones were removed completely at initial therapy.", "author" : [ { "dropping-particle" : "", "family" : "Tadenuma", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ishihara", "given" : "Takeshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamaguchi", "given" : "Taketo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsuchiya", "given" : "Shouichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kobayashi", "given" : "Akitoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakamura", "given" : "Kazuyoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sakurada", "given" : "Reiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saisho", "given" : "Hiromitsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2005", "11" ] ] }, "note" : "NULL", "page" : "1128-35", "title" : "Long-term results of extracorporeal shockwave lithotripsy and endoscopic therapy for pancreatic stones.", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(234)", "plainTextFormattedCitation" : "(234)", "previouslyFormattedCitation" : "(234)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(234).Other factors independently associated with long-term ( 2 years) pain relief that could be taken into consideration for the selection of the best candidates for ESWL ET are a short disease duration prior to treatment, a low frequency of pain attacks before treatment, a complete ductal stone clearance, the absence of MPD stricture and discontinuation of alcohol and tobacco during FUADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1542-3565", "PMID" : "16271345", "abstract" : "BACKGROUND & AIMS The aim of this study was to evaluate the short- and long-term results of extracorporeal shockwave lithotripsy (ESWL) and endoscopic therapy for pancreatic stones. METHODS A total of 117 patients with pancreatic stones underwent ESWL and endoscopic treatment in our institute. Seventy patients who were followed-up for over 3 years after treatment were evaluated retrospectively. RESULTS Immediate pain relief was achieved in 97% and complete removal of stones was achieved in 56%. During the long-term follow-up evaluation, 49 of 70 patients continued to be asymptomatic. Pain recurred more frequently in patients with incomplete removal than in those with complete removal (P < .05). Twenty-one patients who became symptomatic during the follow-up period underwent additional therapy, and pain relief was attained without surgery in all of them. Both endocrine and exocrine function deteriorated after the long-term follow-up period (P < .05). CONCLUSIONS ESWL and endoscopic treatment of pancreatic stones proved to be effective for long-term pain relief, especially in patients in whom stones were removed completely at initial therapy.", "author" : [ { "dropping-particle" : "", "family" : "Tadenuma", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ishihara", "given" : "Takeshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamaguchi", "given" : "Taketo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsuchiya", "given" : "Shouichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kobayashi", "given" : "Akitoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakamura", "given" : "Kazuyoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sakurada", "given" : "Reiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saisho", "given" : "Hiromitsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2005", "11" ] ] }, "note" : "NULL", "page" : "1128-35", "title" : "Long-term results of extracorporeal shockwave lithotripsy and endoscopic therapy for pancreatic stones.", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1080/00365520510024098", "ISSN" : "0036-5521", "PMID" : "16373284", "abstract" : "OBJECTIVE In the past 15 years there have been tremendous advances in endoscopic management of chronic pancreatitis (CP). However, the value of endoscopic pancreatic stenting is still debatable. MATERIAL AND METHODS In 98 patients suffering from symptomatic CP (84 M, 14 F, 49+/-12, age range 23-83 years) endotherapy including temporary stenting of the pancreatic duct was performed. After final stent removal, indicating the primary end-point of endotherapy, 96 patients were followed for 35+/-28 (8 days-111) months. All data were assessed retrospectively. RESULTS As well as other endoscopic procedures, a total of 358 prostheses were inserted in the pancreatic duct and left in place for 3+/-1 (1 day-11) months. Total stent treatment time was 10+/-10 (6 days-49) months. At 46+/-27 (4-111) months after limited endotherapy, 57 patients had no need for secondary intervention, two-thirds were even without further pain sensations. In 22 patients, surgical treatment and in 17 patients further endoscopic therapy became necessary, which was significantly correlated with continued alcohol consumption. CONCLUSIONS Temporary stent placement as a part of interventional endoscopic therapy in CP shows a high rate of technical and long-term clinical success, with no need for secondary treatment in a remarkable number of patients. Continued cessation of alcohol consumption supports the treatment benefit significantly.", "author" : [ { "dropping-particle" : "", "family" : "Farnbacher", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "M\u00fchldorfer", "given" : "Steffen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wehler", "given" : "Markus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fischer", "given" : "Bernhard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hahn", "given" : "Eckhart G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schneider", "given" : "H Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of gastroenterology", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2006", "1", "8" ] ] }, "note" : "NULL", "page" : "111-7", "title" : "Interventional endoscopic therapy in chronic pancreatitis including temporary stenting: a definitive treatment?", "type" : "article-journal", "volume" : "41" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISSN" : "0016-5107", "PMID" : "8781931", "abstract" : "BACKGROUND In severe chronic pancreatitis associated with intraductal stones, therapeutic endoscopy aims to reduce increased intraductal pressure by pancreatic sphincterotomy and stone clearance. METHODS Results of treatment were evaluated in 70 new patients who underwent pancreatic sphincterotomy and attempted stone removal. Technical results and frequency of pain relief and recurrence are compared. RESULTS Complete ductal clearance of calculi was obtained in 50% of cases. Immediate clinical improvement occurred in 95% of patients with painful attacks. No severe complications or mortality occurred. Fifty-four percent of all patients with painful chronic pancreatitis did not experience any pain recurrence within 2 years. Associations found to be statistically significant by multivariate analysis were ductal clearance and extracorporeal shock wave lithotripsy, pain disappearance and ductal clearance, pain recurrence and long evolution, and severe disease before treatment and presence of a ductal substenosis. CONCLUSIONS In this subset of patients our results indicate that the pain of chronic pancreatitis is mainly related to increased intraductal pressure. Endoscopic management appears to be a safe, conservative, alternative to surgery. The best results are obtained when it is performed early in the course of calcifying chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Dumonceau", "given" : "J M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devi\u00e8re", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moine", "given" : "O", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delhaye", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vandermeeren", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baize", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gansbeke", "given" : "D", "non-dropping-particle" : "Van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cremer", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastrointestinal endoscopy", "id" : "ITEM-3", "issue" : "6", "issued" : { "date-parts" : [ [ "1996", "6" ] ] }, "note" : "NULL", "page" : "547-55", "title" : "Endoscopic pancreatic drainage in chronic pancreatitis associated with ductal stones: long-term results.", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "ISSN" : "1542-3565", "PMID" : "15625655", "abstract" : "BACKGROUND & AIMS Endotherapy for patients with painful chronic pancreatitis (CP) gives early and midterm clinical results comparable with those of conventional surgery. The authors evaluated long-term clinical outcome after endoscopic pancreatic ductal drainage, focusing on pain and pancreatic endocrine/exocrine functions. METHODS Of 110 patients with painful CP endoscopically treated between October 1987 and December 1989, 56 long-surviving patients were followed-up for 14.4 years (SD, .6 y); 40 patients died and 14 patients were lost to follow-up evaluation. Technical results included decreased ductal dilation and stone clearance. Clinical results included the rate of hospitalizations for pain before and after endotherapy, the need for surgery, the course of endocrine/exocrine insufficiencies, and late mortality. RESULTS Complete or partial technical success initially was obtained in 48 of 56 long-surviving patients. Long-term clinical success (< or =5 hospitalizations for pain during follow-up evaluation, without surgery) was obtained for 37 of 56 patients. At a mean follow-up time of 14.4 years, 44 patients had avoided surgery and the annual rate of hospitalizations for pain decreased significantly (before endotherapy: 0.98 [+/-1.36] vs 0.40 [+/-0.51] for the 3 years thereafter vs 0.14 [+/-0.22] for the last 11 years of follow-up evaluation; P < .001). Short duration of disease before initial therapy and absence of smoking at the last follow-up evaluation were associated with long-term clinical success. CONCLUSIONS Endotherapy provides long-term benefits for about two thirds of patients with painful CP. Good clinical outcome was associated with cessation or absence of smoking, whereas alcohol abuse increased the risks for diabetes mellitus, steatorrhea, and mortality.", "author" : [ { "dropping-particle" : "", "family" : "Delhaye", "given" : "Myriam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arvanitakis", "given" : "Marianna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Verset", "given" : "Gontran", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cremer", "given" : "Michel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devi\u00e8re", "given" : "Jacques", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association", "id" : "ITEM-4", "issue" : "12", "issued" : { "date-parts" : [ [ "2004", "12" ] ] }, "note" : "NULL", "page" : "1096-106", "title" : "Long-term clinical outcome after endoscopic pancreatic ductal drainage for patients with painful chronic pancreatitis.", "type" : "article-journal", "volume" : "2" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(234,240,251,255)", "plainTextFormattedCitation" : "(234,240,251,255)", "previouslyFormattedCitation" : "(234,240,251,255)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(234,240,251,255).Table 1 : ESWL + Endoscopy – Short term FU < 2 yAuthor (year) (ref)DesignPopulationInterventionOutcomeCommentsDelhaye (1992)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0016-5085", "PMID" : "1732129", "abstract" : "Extracorporeal shock-wave lithotripsy (ESWL) has been used to disintegrate pancreatic stones located in the main pancreatic duct for 123 patients with severe chronic pancreatitis. Endoscopic management following ESWL is aimed at restoring the pancreatic flow to the duodenum. Stone disintegration was achieved in 122 patients, whereas a decrease in the main pancreatic duct diameter resulted in 111, and complete clearance of the main pancreatic duct was obtained in 72. Pain relief, complete (40/88) or partial (35/88), correlated significantly with the results of the endoscopic drainage of the main pancreatic duct (e.g., decrease in main pancreatic duct diameter). Relapsing pain was most often related to recurrent pancreatic duct obstruction. Of 76 patients whose body weight had decreased before ESWL, 54 gained weight. Improvement of the exocrine function, evaluated by the [14C]triolein breath test before and 11 months, on the average, after ESWL, was observed in 12 patients among 22 for whom this test was performed before and after treatment. Improvement of the endocrine function after relief of obstruction of the main pancreatic duct was less frequently recorded (4/41). ESWL of pancreatic stones is a new, safe, and highly effective method of facilitating the endoscopic procedures for relief of pancreatic duct obstruction in severe chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Delhaye", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vandermeeren", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baize", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cremer", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "1992", "2" ] ] }, "note" : "NULL", "page" : "610-20", "title" : "Extracorporeal shock-wave lithotripsy of pancreatic calculi.", "type" : "article-journal", "volume" : "102" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(249)", "plainTextFormattedCitation" : "(249)", "previouslyFormattedCitation" : "(249)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(249)Prospective observational123 patients:81% men, 80% OHAge: 44.8 yDuration of disease: 4.5 ySevere CP: 94%Pain: 87%(Type A: 81%)FU: 14 mDiabetes: 35%Steatorrhea: 28%ESWL, EPSPancreating stenting: 39%Technical success: 90%(111 / 123 MPD )Complete MPD clearance: 59%(72 / 123)Pain relief assessmentPain free intervalComplete pain relief: 40/88Partial pain relief: 35/88Complete or partial pain relief: 85%Surgery: 8%Recurrent pain more frequent when no decrease in MPD LOE?: moderateSchneider (1994)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0002-9270", "PMID" : "7942733", "abstract" : "OBJECTIVES The efficacy of extracorporeal piezoelectric shock wave lithotripsy in patients with obstructing pancreatic duct stones was investigated. METHODS Fifty patients suffering from chronic pancreatitis and obstructing pancreatolithiasis were treated by ESWL (Piezolith 2500). Shock wave treatment was administered, inasmuch as the stones were not extractable by initially applied endoscopic measures. RESULTS A total of 119 (2.4 +/- 1.4, range 1-7) lithotripsy sessions were conducted; only mild sedation/analgesia was used. Optimum targeting of the concrements in the shock wave focus was achieved in 17 (14%) treatment sessions with ultrasonography only; it was achieved in 65 (55%) cases by fluoroscopy and, in further 37 (31%) sessions by using both localization systems. Stone fragmentation was successful in 43 (86%) patients. Nineteen (38%) patients achieved spontaneous stone discharge after shock wave lithotripsy. In 11 (22%) cases, it was possible to remove all fragments endoscopically; residual fragments remained in 20 (40%) patients. Severe complications attributable to shock wave application did not occur. During follow-up, six patients had to be referred to surgery; two male patients died of specific diabetic complications and pleural mesothelioma, respectively. Thirty-five (90%) of 39 patients whose conditions were followed for 2-50 (20 +/- 14) months reported improvement of their pain sensations. Six (15%) patients required endoscopic treatment, including ESWL in five of those patients, to be repeated due to recurrent formation of calculi in the main pancreatic duct, which was again successful in five of the six patients. CONCLUSIONS Piezoelectric shock wave lithotripsy offers a basis for safe and effective fragmentation of pancreatic stones and facilitates endoscopic procedures. Most of the patients with obstructing pancreatic stones became stonefree and showed a significant reduction of pain.", "author" : [ { "dropping-particle" : "", "family" : "Schneider", "given" : "H T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "May", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benninger", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rabenstein", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hahn", "given" : "E G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katalinic", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ell", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American journal of gastroenterology", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "1994", "11" ] ] }, "note" : "NULL", "page" : "2042-8", "title" : "Piezoelectric shock wave lithotripsy of pancreatic duct stones.", "type" : "article-journal", "volume" : "89" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(267)", "plainTextFormattedCitation" : "(267)", "previouslyFormattedCitation" : "(267)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(267)Retrospective observational50 patients78% men, 66% OHAge: 45 yDuration of disease: 4.8 ySevere CP: --Pain: 100%(Type A: 72%)FU: 20 mDiabetes: 38%Steatorrhea: 14%ESWL, EPSPancreating stenting: 26%Technical success: 100%(50 / 50 complete or partial MPD clearance)Complete MPD clearance: 60%(30 / 50)Pain relief assessment pain frequencyComplete pain relief: 24/39 = 62%Partial pain relief: 7/39 = 18%Complete or partial pain relief: 79%Surgery: 12%No predictive factor of pain reliefLOE?: lowBrand (2000)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1572-0241.2000.03190.x", "ISSN" : "0002-9270", "PMID" : "11151873", "abstract" : "OBJECTIVE Therapeutic endoscopy may be effective in selected patients with chronic calcific pancreatitis (CCP). We prospectively evaluated the early outcome of extracorporeal shockwave lithotripsy (ESWL) in combination with interventional endoscopy, using broad inclusion criteria. METHODS A total of 48 consecutive patients (35 male, 13 female) were recruited for ESWL and endoscopic therapy of symptomatic CCP. Symptoms, quality of life, pancreatic morphology and function were assessed before and after. RESULTS Multiple stones (n = 43), strictures (n = 34), and pancreas divisum (n = 11) were found. A median of 13 ESWL sessions (range 2-74) with a median of 22,100 shockwaves (1,700-150,900) were required. Endoscopic pancreatic sphincterotomy (n = 48), stricture dilation (n = 12), and/or stenting (n = 27) were performed. After therapy, drainage of the pancreatic duct system was achieved in 36, complete stone clearance in 21 patients. Follow-up (n = 38) at 7 months (range 5-9) showed a significant decrease in pancreatic duct diameter (p < 0.001) and pain score (p < 0.0001) whereas complete pain relief was observed in 45% of cases. Several quality of life scores improved significantly. Weight gain occurred in 68% of patients. Normalization of fasting blood glucose and HbA1c levels were observed in four patients, without modifying their treatment. Improvement in pain score correlated with weight gain and decrease in pancreatic duct diameter. Nonalcoholic etiology was associated with a better chance for improvement in pain score and decrease in pancreatic duct diameter. The presence of strictures did not deteriorate the clinical outcome. CONCLUSIONS Besides pain relief, ESWL in combination with interventional endoscopy resulted in pancreatic ductal decompression, weight gain, and improvement in quality of life in a considerable number of patients with advanced CCP.", "author" : [ { "dropping-particle" : "", "family" : "Brand", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kahl", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sidhu", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nam", "given" : "V C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Sriram", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jaeckle", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thonke", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Soehendra", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American journal of gastroenterology", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2000", "12" ] ] }, "note" : "NULL", "page" : "3428-38", "title" : "Prospective evaluation of morphology, function, and quality of life after extracorporeal shockwave lithotripsy and endoscopic treatment of chronic calcific pancreatitis.", "type" : "article-journal", "volume" : "95" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(252)", "plainTextFormattedCitation" : "(252)", "previouslyFormattedCitation" : "(252)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(252)Prospective observational48 patients73% men, 64% OHAge: 51 yDuration of disease: 69 mSevere CP: 92%Pain: 98%(Type A: 67%)FU: 7 m (n=38)Diabetes: 33%Steatorrhea: --EPS (n=48)ESWL (n=48)Pancreating stenting: 56%Technical success: --(complete : 60%; complete MPD clearance: 44%)Pain relief assessmentIzbicki pain score improvedComplete pain relief: 17/38 = 45%Partial pain relief: 14/38 = 37%Complete or partial pain relief: 82%Improvement of pain score correlated with in MPD (r = 0.37, p<0.05)Improvement of pain score associated with non-alcoholic CP (RR 1.4, 95% CI 1.1 - 1.8)LOE?: lowKarasawa (2002)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s005350200051", "ISSN" : "0944-1174", "PMID" : "12051536", "abstract" : "BACKGROUND Stones in the main pancreatic duct (MPD) are difficult to remove by endoscopic devices alone in some patients who have chronic pancreatitis. We treated these patients with extracorporeal shock wave lithotripsy (ESWL) and analyzed the patient factors related to disintegration. METHODS Twenty-four patients were treated with ESWL alone or with combined endoscopic-ESWL to disintegrate or remove MPD stones. RESULTS Ten patients were treated by ESWL alone and 14 by combined endoscopic-ESWL. A total of 19 patients (79%) were effectively treated by either method. The mean MPD diameter decreased significantly after ESWL. In most of the patients who had chronic abdominal symptoms, these symptoms were relieved at discharge. Severe side effects of complications did not occur during ESWL therapy. Acute abdominal symptoms and a significant increase in the white blood cell count, total bilirubin, and aspartate aminotransferase were observed only immediately after ESWL. Although there were no significant differences, we observed that the patients with a higher stone disintegration success rate showed the following factors: (1) female, (2) non-alcoholic pancreatitis, (3) younger age, (4) shorter duration of symptoms, (5) smaller stones, and (6) a lower Hounsfield unit value of stones. Although about half of the patients had recurring abdominal symptoms and stones during a follow-up period of 12 months, the stones which caused relapse in short-term intervals were disintegrated easily by ESWL. CONCLUSIONS We may consider the application of ESWL therapies for patients who show the factors associated with easily disintegratable stone conditions. These therapies are highly effective and relatively safe procedures for pancreatic duct stones in such patients.", "author" : [ { "dropping-particle" : "", "family" : "Karasawa", "given" : "Yasuyuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kawa", "given" : "Shigeyuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aoki", "given" : "Yuji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ochi", "given" : "Yasuhide", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Unno", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kiyosawa", "given" : "Kendo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Tomofumi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of gastroenterology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2002", "5", "1" ] ] }, "note" : "NULL", "page" : "369-75", "title" : "Extracorporeal shock wave lithotripsy of pancreatic duct stones and patient factors related to stone disintegration.", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(268)", "plainTextFormattedCitation" : "(268)", "previouslyFormattedCitation" : "(268)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(268)Retrospective24 patients79% men, 71% OHAge: 53 yDuration of disease: 4.4 ySevere CP: --Pain: 83% (20/24)FU: 12 mDiabetes: 50%Steatorrhea: --ESWL alone (n=10)ESWL + Endoscopy (n=14)Technical success: 79%(complete : 19/24; complete MPD clearance: 13/24 = 54%)Pain relief assessment: NAImmediate pain reliefComplete: 19/20 = 95%Sustained pain relief at 12 mComplete: 11/24 = 46%No factor identified for predicting stone(s) disintegrationLOE?: very lowTandan (2010)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s12664-010-0035-y", "ISSN" : "0975-0711", "PMID" : "20717860", "abstract" : "AIM Large pancreatic ductal calculi and pain are a feature of chronic calcific pancreatitis (CCP) in the tropics. This large single center study evaluates the role of extracorporeal shock wave lithotripsy (ESWL) in fragmentation of large pancreatic stones and relief of pain in patients with CCP. METHODS Patients with CCP presenting with pain and large pancreatic duct (PD) calculi (>5\u00a0mm diameter) not amenable to extraction at routine endoscopic retrograde cholangio pancreatography (ERCP) were taken up for ESWL using a 3rd generation lithotripter. Stones in the head and body of pancreas were targeted at ESWL; 5,000 shocks were given per session. The calculi were fragmented to <3\u00a0mm size and then cleared by endotherapy. Pancreatic duct stents were deployed when indicated. A total of 1,006 patients underwent ESWL. Complete clearance was achieved in 762 (76%), partial clearance in 173 (17%) and unsuccessful in the rest. More than 962 (90%) of patients needed less than three sessions of ESWL. At 6\u00a0months, 711 (84%) of 846 patients who returned for follow up had significant relief of pain with a decrease in analgesic use. Complications were mild and minimal. CONCLUSION ESWL is an effective and safe modality for fragmentation of large PD calculi in patients with CCP.", "author" : [ { "dropping-particle" : "", "family" : "Tandan", "given" : "Manu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reddy", "given" : "Duvvuru Nageshwar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Santosh", "given" : "Darisetty", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vinod", "given" : "Koppoju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramchandani", "given" : "Mohan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rajesh", "given" : "Gupta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rama", "given" : "Kotla", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lakhtakia", "given" : "Sandeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banerjee", "given" : "Rupa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pratap", "given" : "Nitesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Venkat Rao", "given" : "Guduru", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2010", "7", "18" ] ] }, "note" : "NULL", "page" : "143-8", "title" : "Extracorporeal shock wave lithotripsy and endotherapy for pancreatic calculi-a large single center experience.", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(269)", "plainTextFormattedCitation" : "(269)", "previouslyFormattedCitation" : "(269)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(269)Prospective observational1006 patients66% men, 8% OHAge: --Duration of disease: 1.7 ySevere CP: 100%Pain: 100%FU: 6 mDiabetes: 32%Steatorrhea: 7%ESWL (n = 1006)EPS (n = 938)Pancreatic stenting(n = 542, 54%)Duration of pancreatic stenting: 6 mTechnical success: 93% (complete or partial ductal clearance)Complete MPD clearance: 76%Pain relief assessment VAS analgesic use/mComplete pain relief: 326/846 = 39%Complete or partial pain relief: 711/846 = 84%Surgery: 38/846 = 4.5%LOE?: moderateMilovic (2011)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.gie.2011.07.062", "ISSN" : "1097-6779", "PMID" : "21981815", "abstract" : "BACKGROUND Extracorporeal shock wave lithotripsy (ESWL) of pancreatic duct stones followed by ERCP with mechanical clearance of the pancreatic duct and subsequent stenting is an established treatment option for chronic calcific pancreatitis. OBJECTIVE To test the efficacy of a modified transportable mini-lithotripter for ESWL of pancreatic duct stones. DESIGN Prospective single-center study. SETTING University hospital. PATIENTS This study involved 32 patients with obstructive chronic calcific pancreatitis and pain in whom previous endoscopic stone removal and pancreatic duct decompression had failed. INTERVENTIONS ESWL followed by ERCP for stone clearance of the pancreatic duct and mechanical removal of stones or stenting. MAIN OUTCOME MEASUREMENTS Endoscopic duct clearance and/or stent insertion, pain and quality-of-life scores. RESULTS A median of 4 ESWL sessions (interquartile range 2.75-8.5) with a median of 6800 shock waves (4225-15,425) were required. Pain relief after ESWL only was noted in 24 patients (75.0%), whereas no change in the intensity of pain was reported by 7 patients (21.9%), and pain was worse in 1 patient. All patients underwent ERCP and stent placement, resulting in complete resolution of pain in 17 patients (53.1%) and pain improvement in 28 patients (87.5%). The quality-of-life score was significantly improved after ESWL and endoscopic clearance or stenting in all patients. LIMITATIONS Uncontrolled study. CONCLUSIONS ESWL with the mini-lithotripter results in fragmentation of pancreatic duct calculi. ESWL in conjunction with endoscopic clearance of the pancreatic duct and stenting is associated with significant improvement in clinical outcome and quality of life in patients with obstructive calcific chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Milovic", "given" : "Vladan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wehrmann", "given" : "Till", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dietrich", "given" : "Christoph F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bailey", "given" : "Adam A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caspary", "given" : "Wolfgang F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Braden", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastrointestinal endoscopy", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2011", "12" ] ] }, "note" : "NULL", "page" : "1294-9", "title" : "Extracorporeal shock wave lithotripsy with a transportable mini-lithotripter and subsequent endoscopic treatment improves clinical outcome in obstructive calcific chronic pancreatitis.", "type" : "article-journal", "volume" : "74" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(270)", "plainTextFormattedCitation" : "(270)", "previouslyFormattedCitation" : "(270)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(270)Prospective32 patients75% men, 81% OHAge: 48 yDuration of disease: --Severe CP: 100%Pain: 100%FU: 6-9 mDiabetes: --Steatorrhea: --ESWL (n=32)Pancreatic stenting: 19/32 (59%)Technical success: 100%(decompression of the MPD)Complete MPD clearance: 41%Pain relief assessment5-point Likert scale pain scoreImmediate pain relief: 24/32 = 75%At 6-9 m after ET, improvement in pain score: 28/32 = 88%Complete pain relief: 17/32 = 53%Improvement of pain score not associated with complete MPD clearanceLOE: lowKawaguchi (2013)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.4172/2165-7092.S3-002", "ISSN" : "21657092", "abstract" : "Background: Methods of pancreatic duct (PD) drainage for recurrent chronic pancreatitis (CP) include endoscopic drainage combined with ESWL and surgical drainage. Although the endoscopic drainage has become widespread as this method is minimally invasive, there are cases in which stent removal is difficult. We retrospectively examined the current status of endoscopic drainage for recurrent CP at our hospital. Methods: This study included 66 patients with recurrent CP (57 men and 9 women with a mean age of 59 \u00b1 14 years, including 58 patients with alcoholic CP) who underwent endoscopic drainage between April 2006 and April 2012. Based on the initial images of PD, the patients were classified into the following types to compare their backgrounds and treatment processes: pancreatolithiasis (Stone) type (7 patients), PD stenosis (Stenosis) type (18), and Stone+Stenosis type (41). Moreover, patients with PD stent were divided into the following groups to compare their backgrounds and treatment processes: stent-removed groupand stent-maintained group in which the stent could not be removed. Results: The procedure was successful in 61 patients (92%). Complete pain relief without analgesics was achieved in 60 patients (91%). The early complications were post-ERCP pancreatitis in 11 patients (2.7%, all mild in severity), and hemorrhage, basket impaction, and rupture of the pancreatic duct in 1 patient (0.5%) each. The late complications were pancreatic ductitis (0.7%), stent displacement (0.5%), stent migration (1.5%), and tear during removal of stent (1%). In Stone type patients, the mean number of procedural sessions and the number of patients who required at least 1 year of treatment were significantly smaller thanin those withPD stenosis (Stenosis type or Stone+Stenosis type) (P=0.0133 and P=0.0043, respectively). Patients with Stenosis type had a significantly smaller mean number of procedural sessions (P=0.0423) and a significantly lower incidence of complications (P=0.0366) than those with Stone+Stenosis type. Comparison between the stent-removed and stent-maintained groups revealed no significant differences in the mean number of procedural sessions, the number of patients with implantation of a stent with a diameter (thicker than 8.5-Fr), or the incidence of complications. In the stent-removed group, the number of patients who required at least 1 year of treatment was significantly smaller (P=0.0285). Conclusions: In the short term, endoscopic stenting \u2026", "author" : [ { "dropping-particle" : "", "family" : "Kawaguchi", "given" : "Yoshiaki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ogawa", "given" : "Masami", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maruno", "given" : "Atsuko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yuhara", "given" : "Hiroki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ito", "given" : "Hiroyuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mine", "given" : "Tetsuya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreatic Disorders & Therapy", "id" : "ITEM-1", "issue" : "03", "issued" : { "date-parts" : [ [ "2013" ] ] }, "publisher" : "OMICS International", "title" : "Strategy of Endoscopic Pancreatic Duct Drainage for Recurrent Chronic Pancreatitis", "type" : "article-journal", "volume" : "03" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(271)", "plainTextFormattedCitation" : "(271)", "previouslyFormattedCitation" : "(271)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(271)retrospective66 patients86% men, 88% OHAge: 59 yDuration of disease: -Severe CP: 100%Pain: 100%FU: NDDiabetes: --Steatorrhea: --ESWL: 41/66 = 62%Pancreatic duct stenting: 51/66 = 77%Technical success: 61/66 = 92%Pain relief assessment: NAComplete pain relief: 60/66 = 91%Partial pain relief: 5/66 = 7%Complete or partial pain relief: 98%In patients with only stonesLower number of proceduresFewer patients who required at least 1 y of treatmentLOE: very lowTable 1S= ESWL + Endoscopy – Short term FU < 2 y – Studies 50 patientsAuthor (year) (ref)DesignNumber of patientsComplete or partial pain reliefFU (months)Comments (LOE)Delhaye (1992)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0016-5085", "PMID" : "1732129", "abstract" : "Extracorporeal shock-wave lithotripsy (ESWL) has been used to disintegrate pancreatic stones located in the main pancreatic duct for 123 patients with severe chronic pancreatitis. Endoscopic management following ESWL is aimed at restoring the pancreatic flow to the duodenum. Stone disintegration was achieved in 122 patients, whereas a decrease in the main pancreatic duct diameter resulted in 111, and complete clearance of the main pancreatic duct was obtained in 72. Pain relief, complete (40/88) or partial (35/88), correlated significantly with the results of the endoscopic drainage of the main pancreatic duct (e.g., decrease in main pancreatic duct diameter). Relapsing pain was most often related to recurrent pancreatic duct obstruction. Of 76 patients whose body weight had decreased before ESWL, 54 gained weight. Improvement of the exocrine function, evaluated by the [14C]triolein breath test before and 11 months, on the average, after ESWL, was observed in 12 patients among 22 for whom this test was performed before and after treatment. Improvement of the endocrine function after relief of obstruction of the main pancreatic duct was less frequently recorded (4/41). ESWL of pancreatic stones is a new, safe, and highly effective method of facilitating the endoscopic procedures for relief of pancreatic duct obstruction in severe chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Delhaye", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vandermeeren", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baize", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cremer", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "1992", "2" ] ] }, "note" : "NULL", "page" : "610-20", "title" : "Extracorporeal shock-wave lithotripsy of pancreatic calculi.", "type" : "article-journal", "volume" : "102" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(249)", "plainTextFormattedCitation" : "(249)", "previouslyFormattedCitation" : "(249)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(249) Prospective12385% (75 / 88)ITT: 75 / 123 = 61%14Recurrent pain more frequent when no decrease in MPD LOE: moderateSchneider (1994)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0002-9270", "PMID" : "7942733", "abstract" : "OBJECTIVES The efficacy of extracorporeal piezoelectric shock wave lithotripsy in patients with obstructing pancreatic duct stones was investigated. METHODS Fifty patients suffering from chronic pancreatitis and obstructing pancreatolithiasis were treated by ESWL (Piezolith 2500). Shock wave treatment was administered, inasmuch as the stones were not extractable by initially applied endoscopic measures. RESULTS A total of 119 (2.4 +/- 1.4, range 1-7) lithotripsy sessions were conducted; only mild sedation/analgesia was used. Optimum targeting of the concrements in the shock wave focus was achieved in 17 (14%) treatment sessions with ultrasonography only; it was achieved in 65 (55%) cases by fluoroscopy and, in further 37 (31%) sessions by using both localization systems. Stone fragmentation was successful in 43 (86%) patients. Nineteen (38%) patients achieved spontaneous stone discharge after shock wave lithotripsy. In 11 (22%) cases, it was possible to remove all fragments endoscopically; residual fragments remained in 20 (40%) patients. Severe complications attributable to shock wave application did not occur. During follow-up, six patients had to be referred to surgery; two male patients died of specific diabetic complications and pleural mesothelioma, respectively. Thirty-five (90%) of 39 patients whose conditions were followed for 2-50 (20 +/- 14) months reported improvement of their pain sensations. Six (15%) patients required endoscopic treatment, including ESWL in five of those patients, to be repeated due to recurrent formation of calculi in the main pancreatic duct, which was again successful in five of the six patients. CONCLUSIONS Piezoelectric shock wave lithotripsy offers a basis for safe and effective fragmentation of pancreatic stones and facilitates endoscopic procedures. Most of the patients with obstructing pancreatic stones became stonefree and showed a significant reduction of pain.", "author" : [ { "dropping-particle" : "", "family" : "Schneider", "given" : "H T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "May", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benninger", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rabenstein", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hahn", "given" : "E G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katalinic", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ell", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American journal of gastroenterology", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "1994", "11" ] ] }, "note" : "NULL", "page" : "2042-8", "title" : "Piezoelectric shock wave lithotripsy of pancreatic duct stones.", "type" : "article-journal", "volume" : "89" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(267)", "plainTextFormattedCitation" : "(267)", "previouslyFormattedCitation" : "(267)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(267)Retrospective5079% (31 / 39)ITT: 31 / 50 = 62%20--LOE: lowTandan (2010) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s12664-010-0035-y", "ISSN" : "0975-0711", "PMID" : "20717860", "abstract" : "AIM Large pancreatic ductal calculi and pain are a feature of chronic calcific pancreatitis (CCP) in the tropics. This large single center study evaluates the role of extracorporeal shock wave lithotripsy (ESWL) in fragmentation of large pancreatic stones and relief of pain in patients with CCP. METHODS Patients with CCP presenting with pain and large pancreatic duct (PD) calculi (>5\u00a0mm diameter) not amenable to extraction at routine endoscopic retrograde cholangio pancreatography (ERCP) were taken up for ESWL using a 3rd generation lithotripter. Stones in the head and body of pancreas were targeted at ESWL; 5,000 shocks were given per session. The calculi were fragmented to <3\u00a0mm size and then cleared by endotherapy. Pancreatic duct stents were deployed when indicated. A total of 1,006 patients underwent ESWL. Complete clearance was achieved in 762 (76%), partial clearance in 173 (17%) and unsuccessful in the rest. More than 962 (90%) of patients needed less than three sessions of ESWL. At 6\u00a0months, 711 (84%) of 846 patients who returned for follow up had significant relief of pain with a decrease in analgesic use. Complications were mild and minimal. CONCLUSION ESWL is an effective and safe modality for fragmentation of large PD calculi in patients with CCP.", "author" : [ { "dropping-particle" : "", "family" : "Tandan", "given" : "Manu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reddy", "given" : "Duvvuru Nageshwar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Santosh", "given" : "Darisetty", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vinod", "given" : "Koppoju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramchandani", "given" : "Mohan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rajesh", "given" : "Gupta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rama", "given" : "Kotla", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lakhtakia", "given" : "Sandeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banerjee", "given" : "Rupa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pratap", "given" : "Nitesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Venkat Rao", "given" : "Guduru", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2010", "7", "18" ] ] }, "note" : "NULL", "page" : "143-8", "title" : "Extracorporeal shock wave lithotripsy and endotherapy for pancreatic calculi-a large single center experience.", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(269)", "plainTextFormattedCitation" : "(269)", "previouslyFormattedCitation" : "(269)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(269)Prospective100684% (711 / 846)ITT: 711 / 1006 = 71%6--LOE: moderateTotal117984% (79 - 85)ITT: 817 / 1179 = 69%Table 2 : ESWL + Endoscopy – Medium term FU 2 – 5 yAuthor (year) (ref)DesignPopulationInterventionOutcomeCommentsSauerbruch (1992)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0017-5749", "PMID" : "1644340", "abstract" : "Extracorporeal shock wave lithotripsy of pancreatic duct stones (largest stone 12 (SD) 6 mm) was performed in 24 patients with abdominal pain and a dilated duct system (main pancreatic duct 10 (3) mm). The procedure was well tolerated in all but two patients, who had a mild pancreatitic attack immediately after lithotripsy. Disintegration of the stones was achieved in 21 patients. This allowed complete clearance of the duct system by an endoscopic approach in 10 (42%) patients and partial clearance in 7 (29%) patients. Within a mean follow up period of 24 (14) months half of the patients showed complete or considerable relief of pain and alleviation of symptoms was achieved in seven patients. Relief of pain occurred more often after complete ductal clearance. There were no fatalities within the follow up period. These findings underline the value of a combined non-surgical approach, using endoscopy and adjuvant shock wave lithotripsy to patients with large pancreatic calculi and pain attacks.", "author" : [ { "dropping-particle" : "", "family" : "Sauerbruch", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holl", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sackmann", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Paumgartner", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gut", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "1992", "7" ] ] }, "note" : "NULL", "page" : "969-72", "title" : "Extracorporeal lithotripsy of pancreatic stones in patients with chronic pancreatitis and pain: a prospective follow up study.", "type" : "article-journal", "volume" : "33" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(250)", "plainTextFormattedCitation" : "(250)", "previouslyFormattedCitation" : "(250)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(250)Retrospective observational24 patients:83% men, 63% OHAge: 46 yDuration of disease: 5 ySevere CP: --Pain: 100%FU: 24 mDiabetes: --Steatorrhea: --ESWL, EPSPancreating stenting: 8%Technical success: 67%Complete MPD clearance: 42%(10 / 24)Pain relief assessment pain frequency/mComplete pain relief: 12/24Partial pain relief: 8/24Complete or partial pain relief: 83%Surgery: 8%Pain relief more often in patients with complete stone clearance (9/10 vs 3/14)No statistical analysisLOE?: lowCostamagna (1997)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0016-5107", "PMID" : "9378210", "abstract" : "BACKGROUND Obstruction of the main pancreatic duct with upstream hypertension and dilation is a cause of pain in patients with chronic pancreatitis. Pancreatic ductal drainage can be achieved endoscopically by intraductal stone removal after endoscopic pancreatic sphincterotomy and/or by insertion of a pancreatic stent. Extracorporeal shock wave lithotripsy may be needed whenever stones cannot be removed by endoscopic procedures. We present our results in 35 patients treated with a combined endoscopic-extracorporeal shock wave lithotripsy approach with at least 6 months of follow-up. METHODS Thirty-five patients with severe chronic pancreatitis were treated by extracorporeal shock wave lithotripsy for endoscopically unretrievable obstructive stones. Extracorporeal shock wave lithotripsy was performed with an electromagnetic lithotriptor in 29 patients and an electrohydraulic lithotriptor in 6. RESULTS The procedures were well tolerated by the majority of patients. Fragmentation of stones was obtained in all cases while complete clearance and decompression of pancreatic duct were obtained in 26 of 35 (74.3%) and in 30 of 35 (85.7%) cases, respectively. There was no mortality related to the procedure. Morbidity was observed in 8 of 35 patients (22.8%). CONCLUSIONS Extracorporeal shock wave lithotripsy is a safe and effective treatment for endoscopically unretrievable pancreatic stones in the main pancreatic duct. Extracorporeal shock wave lithotripsy should be considered complementary and not an alternative to endoscopic drainage. Combined with endoscopy, extracorporeal shock wave lithotripsy may increase the success rate of nonsurgical treatment of patients with chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Costamagna", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gabbrielli", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mutignani", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perri", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pandolfi", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boscaini", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crucitti", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastrointestinal endoscopy", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "1997", "9" ] ] }, "note" : "NULL", "page" : "231-6", "title" : "Extracorporeal shock wave lithotripsy of pancreatic stones in chronic pancreatitis: immediate and medium-term results.", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(272)", "plainTextFormattedCitation" : "(272)", "previouslyFormattedCitation" : "(272)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(272)Prospective observational35 patients:89% men, 83% OHAge: 46.3 yDuration of disease: 3.3 ySevere CP: 95%Pain: 100%FU (n=32): 26.8 mDiabetes: 37%Steatorrhea: 11%ESWL (n=35)EPS (n=34)Pancreating stenting: 51%Technical success: 86%( MPD )Complete MPD clearance: 74%Pain relief assessment: NAComplete pain relief: 23/32 = 72%LOE?: lowAdamek (1999)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0017-5749", "PMID" : "10446109", "abstract" : "BACKGROUND There have been conflicting reports as to whether pancreatic ductal drainage achieved by endoscopy and lithotripsy improves the clinical outcome of patients with chronic pancreatitis. AIMS To determine the clinical outcome in patients with chronic pancreatitis who received extracorporeal shock wave lithotripsy (ESWL), and were followed up for two to eight years. METHODS Eighty patients with severe chronic pancreatitis and endoscopically unretrievable obstructive stones underwent ESWL with a piezoelectric lithotripter between 1989 and 1996. Clinical status, relief of symptoms, further endoscopic or surgical interventions, and mortality were defined. RESULTS Forty three (54%) patients were treated successfully with ESWL. The only feature associated with treatment success was the presence of a single stone rather than multiple stones. Successfully treated patients tended to experience less pain, although this did not reach statistical significance. A slight increase in weight was noted in our patients; however, there was no notable improvement in anomalous stools and diabetes mellitus. Five patients died due to extrapancreatic reasons. No pancreatic carcinomas developed. CONCLUSIONS ESWL associated with endoscopic drainage is a safe technique that is particularly successful in patients with a single stone. However, pancreatic drainage by endoscopy and ESWL has almost no effect on pain in chronic pancreatitis. Furthermore, endoscopic management and ESWL does not prevent or postpone the development of glandular insufficiency.", "author" : [ { "dropping-particle" : "", "family" : "Adamek", "given" : "H E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jakobs", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buttmann", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adamek", "given" : "M U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schneider", "given" : "A R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Riemann", "given" : "J F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gut", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "1999", "9" ] ] }, "note" : "NULL", "page" : "402-5", "title" : "Long term follow up of patients with chronic pancreatitis and pancreatic stones treated with extracorporeal shock wave lithotripsy.", "type" : "article-journal", "volume" : "45" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(265)", "plainTextFormattedCitation" : "(265)", "previouslyFormattedCitation" : "(265)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(265)Retrospective observational80 patients:78% men, 75% OHAge: --Duration of disease: --Severe CP: --Pain: 100%FU: 40 mDiabetes: 26%Steatorrhea: 24%ESWL (n=80)Pancreating stenting: NATechnical success: 43/80 = 54%(complete or partial MPD clearance + pancreatic stenting)Pain relief assessment: NAComplete or partial pain relief: 61/80 = 76%No analgesia: 43/80 = 54%Surgery: 8/80 = 10%No association between clinical improvement and technical successLOE?: lowFarnbacher (2002)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1067/mge.2002.128162", "ISSN" : "0016-5107", "PMID" : "12297764", "abstract" : "BACKGROUND The aim of the study was to evaluate interventional endoscopic management of pancreatic duct stones in patients with chronic pancreatitis by describing therapeutic methods and defining factors that predict technical success. METHODS Records were retrospectively analyzed for 125 patients with symptoms caused by chronic pancreatitis with pancreatic duct stones (single 43, multiple 82) treated by interventional endoscopy, including extracorporeal shockwave lithotripsy. RESULTS Technical success was achieved in 85% of patients (11 patients by mechanical lithotripsy, 114 by piezoelectric extracorporeal shockwave lithotripsy). There were no serious complications from lithotripsy. Univariate analysis disclosed a statistically significant association between treatment success and patient age as well as prepapillary location of stones. A greater therapeutic effort was necessary in patients with stones located in the tail of the pancreas, 2 or more stones, a stone 12 mm or more in diameter, or who have had a longer duration (>8 years) of the disease. However, with exception of the last parameter, correction for multiple testing of data removed statistical significance. CONCLUSIONS Extracorporeal shockwave lithotripsy enhances endoscopic measures for treatment of pancreatic duct stones when mechanical lithotripsy fails. Middle-aged patients in the early stages of chronic pancreatitis with stones in a prepapillary location proved to be the best candidates for successful treatment. Unfavorable patient-related or morphologic factors can be compensated for through more intense efforts at therapy.", "author" : [ { "dropping-particle" : "", "family" : "Farnbacher", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schoen", "given" : "Christoph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rabenstein", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benninger", "given" : "Johannes", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hahn", "given" : "Eckhart G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schneider", "given" : "H Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastrointestinal endoscopy", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2002", "10" ] ] }, "note" : "NULL", "page" : "501-6", "title" : "Pancreatic duct stones in chronic pancreatitis: criteria for treatment intensity and success.", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(235)", "plainTextFormattedCitation" : "(235)", "previouslyFormattedCitation" : "(235)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(235)Retrospective observational125 patients:81% men, 66% OHAge: 48 yDuration of disease: 5.9 ySevere CP: --Pain: 86%(Type A: 72%)FU (n=84): 29 mDiabetes: --Steatorrhea: --ESWL (n=114)Pancreatic stenting (n=70)Technical success: 85% (106/125)Complete MPD clearance: 64/125 = 51%Pain relief assessment: NAImmediate pain reliefComplete: 94/101 = 93%Sustained pain reliefComplete: 40/84 = 48%Surgery: 15/114 = 13%No association between relapse of pain (44/84) andContinued consumption of alcoholComplete vs partial MPD clearanceLOE: lowKozarek (2002)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1067/mge.2002.128105", "ISSN" : "0016-5107", "PMID" : "12297763", "abstract" : "BACKGROUND There is controversy as to whether extracorporeal shock wave lithotripsy fragmentation and ERCP retrieval of pancreatic stones are associated with relief of chronic pain or relapsing attacks of pancreatitis. Our most recent experience with this technology is reviewed. METHODS Forty patients with chronic calcific pancreatitis who required extracorporeal shock wave lithotripsy between 1995 and 2000 to facilitate pancreatic duct stone removal were retrospectively reviewed. Data collected included patient presentation, number of lithotripsy and ERCP sessions required, complications, and outcomes measures to include pre- and post-ESWL pain scale, monthly oxycodone (5 mg)-equivalent pills ingested, yearly hospitalizations, and need for subsequent surgery. RESULTS A single extracorporeal shock wave lithotripsy session was required for 35 patients who underwent a total of 86 ERCPs to achieve complete stone extraction from the main pancreatic duct. Minor complications occurred in 20%. There was one episode of pancreatic sepsis that was treated with antibiotics and removal of an occluded pancreatic prosthesis. At a mean [SD] follow-up of 2.4 (0.6) years, 80% of patients had avoided surgery and there was a statistically significant decrease in pain scores (6.9 [1.3] vs. 2.9 [1.1]; p = 0.001), yearly hospitalizations for pancreatitis (3.9 [1.9] vs. 0.9 [0.9]; p = 0.001), and oxycodone-equivalent narcotic medication ingested monthly (125 [83] vs. 81 [80]; p = 0.03). CONCLUSIONS Extracorporeal shock wave lithotripsy fragmentation of pancreatic duct calculi in conjunction with endoscopic clearance of the main pancreatic duct is associated with significant improvement in clinical outcomes in most patients with chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Kozarek", "given" : "Richard A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brandabur", "given" : "John J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ball", "given" : "Terrence J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gluck", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Patterson", "given" : "David J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Attia", "given" : "Fouad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "France", "given" : "Renee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Traverso", "given" : "L William", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koslowski", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gibbons", "given" : "Robert P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastrointestinal endoscopy", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2002", "10" ] ] }, "note" : "NULL", "page" : "496-500", "title" : "Clinical outcomes in patients who undergo extracorporeal shock wave lithotripsy for chronic calcific pancreatitis.", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(273)", "plainTextFormattedCitation" : "(273)", "previouslyFormattedCitation" : "(273)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(273)Retrospective observational40 patients:53% men, 58% OHAge: 53 yDuration of disease: 5.9 ySevere CP: --Pain: 100%FU: 2.4 yDiabetes: --Steatorrhea: 10%ESWL (n=40)EPS (n=40)Pain relief assessment VAS yearly hospitalizations narcotic medication monthlyComplete or partial pain relief: 32/40 = 80%Surgery: 20%LOE: lowInui (2005)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1536-4828", "PMID" : "15632696", "abstract" : "OBJECTIVES A retrospective multicenter survey was performed to evaluate the efficacy of extracorporeal shock wave lithotripsy (ESWL) as a treatment of pancreatic stones. METHODS A survey was sent to 11 institutions belonging to the Japanese Association of Extracorporeal Shock Wave Lithotripsy in Digestive Diseases, and data were collected on 555 patients who underwent ESWL for pancreatic stones between January 1990 and September 2002. The male:female ratio was 5.2:1, and the mean age was 52.5 years. The etiology was alcohol related in 425 patients (76.6%) and idiopathic in 111 patients (20.0%); 204 patients (36.8%) had a single stone and 470 patients (84.7%) were symptomatic. RESULTS Mean frequency of the procedure was 5.0 times (range, 1-29). Fragmentation of stones was achieved in 513 patients (92.4%), and the complete stone clearance rate after ESWL alone or in combination with interventional endoscopy was 72.6%. Symptom relief was achieved in 428 (91.1%) of 470 patients. Thirty-five patients (6.3%) developed complications, including 30 patients (5.4%) who developed acute pancreatitis. Five hundred four (90.8%) patients were followed for a mean of 44.3 months, during which 122 (22.0%) suffered stone recurrence (mean time to recurrence, 25.1 months). Twenty-two (4.1%) of the 504 patients who were followed required surgery. Pancreatic exocrine function improved in 65 patients (38.0%), was unchanged in 49 patients (28.7%), and progressed in 57 patients (33.3%). Pancreatic endocrine function improved in 44 patients (24.3%), was unchanged in 85 patients (47.0%), and progressed in 52 patients (28.7%). CONCLUSION ESWL is the treatment of choice for clearing pancreatic stones.", "author" : [ { "dropping-particle" : "", "family" : "Inui", "given" : "Kazuo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tazuma", "given" : "Susumu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamaguchi", "given" : "Taketo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ohara", "given" : "Hirotaka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsuji", "given" : "Tadao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyagawa", "given" : "Hiroyuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Igarashi", "given" : "Yoshinori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakamura", "given" : "Yuta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atomi", "given" : "Yutaka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreas", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2005", "1" ] ] }, "note" : "NULL", "page" : "26-30", "title" : "Treatment of pancreatic stones with extracorporeal shock wave lithotripsy: results of a multicenter survey.", "type" : "article-journal", "volume" : "30" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(263)", "plainTextFormattedCitation" : "(263)", "previouslyFormattedCitation" : "(263)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(263)Retrospective multicenter: 11 centers555 patients:84% men, 77% OHAge: 52.5 yDuration of disease: --Severe CP: --Pain: 85%FU (n=504): 44.3 mDiabetes: --Steatorrhea: --ESWL alone: n=318ESWL + Endoscopy: n=237Technical success: --Complete MPD clearance: 403/555 = 73%Pain relief assessment: NAComplete or partial pain relief: 382/504 = 76%Surgery: 22/504 = 4%LOE: lowCahen (2007)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1056/NEJMoa060610", "ISSN" : "0028-4793", "PMID" : "17301298", "abstract" : "BACKGROUND For patients with chronic pancreatitis and a dilated pancreatic duct, ductal decompression is recommended. We conducted a randomized trial to compare endoscopic and surgical drainage of the pancreatic duct. METHODS All symptomatic patients with chronic pancreatitis and a distal obstruction of the pancreatic duct but without an inflammatory mass were eligible for the study. We randomly assigned patients to undergo endoscopic transampullary drainage of the pancreatic duct or operative pancreaticojejunostomy. The primary end point was the average Izbicki pain score during 2 years of follow-up. The secondary end points were pain relief at the end of follow-up, physical and mental health, morbidity, mortality, length of hospital stay, number of procedures undergone, and changes in pancreatic function. RESULTS Thirty-nine patients underwent randomization: 19 to endoscopic treatment (16 of whom underwent lithotripsy) and 20 to operative pancreaticojejunostomy. During the 24 months of follow-up, patients who underwent surgery, as compared with those who were treated endoscopically, had lower Izbicki pain scores (25 vs. 51, P<0.001) and better physical health summary scores on the Medical Outcomes Study 36-Item Short-Form General Health Survey questionnaire (P=0.003). At the end of follow-up, complete or partial pain relief was achieved in 32% of patients assigned to endoscopic drainage as compared with 75% of patients assigned to surgical drainage (P=0.007). Rates of complications, length of hospital stay, and changes in pancreatic function were similar in the two treatment groups, but patients receiving endoscopic treatment required more procedures than did patients in the surgery group (a median of eight vs. three, P<0.001). CONCLUSIONS Surgical drainage of the pancreatic duct was more effective than endoscopic treatment in patients with obstruction of the pancreatic duct due to chronic pancreatitis. (Current Controlled Trials number, ISRCTN04572410 [controlled-].).", "author" : [ { "dropping-particle" : "", "family" : "Cahen", "given" : "Djuna L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gouma", "given" : "Dirk J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nio", "given" : "Yung", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rauws", "given" : "Erik A. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boermeester", "given" : "Marja A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Busch", "given" : "Olivier R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stoker", "given" : "Jaap", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lam\u00e9ris", "given" : "Johan S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dijkgraaf", "given" : "Marcel G.W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huibregtse", "given" : "Kees", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruno", "given" : "Marco J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "New England Journal of Medicine", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2007", "2", "15" ] ] }, "page" : "676-684", "title" : "Endoscopic versus Surgical Drainage of the Pancreatic Duct in Chronic Pancreatitis", "type" : "article-journal", "volume" : "356" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(232)", "plainTextFormattedCitation" : "(232)", "previouslyFormattedCitation" : "(232)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(232)Prospective randomized controlled trial39 patients19 ET58% men, 37% OHAge: 52 yDuration of disease: 16 mSevere CP: 100%Pain: 100%(Type A: 37%)FU: 2 yDiabetes: 21%Steatorrhea: 68%19 endoscopy / 20 surgery16 ESWL (84%)EPSPancreatic stenting: 16/19 = 84%Median duration of stenting: 6.2 mComplete MPD clearance: 16/18 = 89%Technical success: 53%Pain relief assessmentIzbicki pain score at 6 w, 3, 6, 12, 18, 24 mComplete pain relief: 3/19 = 16%Partial pain relief: 3/19 = 16%Complete or partial pain relief: 32%Surgery: 4/19 = 21%Low technical success rate (53%)Low duration of pancreatic stenting (6.2 m)ESWL and ET performed in different hospitalsLOE: highDumonceau (2007)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/gut.2006.096883", "ISSN" : "0017-5749", "PMID" : "17047101", "abstract" : "BACKGROUND In chronic pancreatitis, obstruction of the main pancreatic duct (MPD) may contribute to the pathogenesis of pain. Pilot studies suggest that extracorporeal shock wave lithotripsy (ESWL) alone relieves pain in calcified chronic pancreatitis. AIM To compare ESWL alone with ESWL and endoscopic drainage of the MPD for treatment of pain in chronic pancreatitis. SUBJECTS Patients with uncomplicated painful chronic pancreatitis and calcifications obstructing the MPD. METHODS 55 patients were randomised to ESWL alone (n = 26) or ESWL combined with endoscopy (n = 29). RESULTS 2 years after trial intervention, 10 (38%) and 13 (45%) patients of the ESWL alone and ESWL combined with endoscopy group, respectively, had presented pain relapse (primary outcome) (OR 0.77; 95% CI 0.23 to 2.57). In both groups, a similar decrease was seen after treatment in the MPD diameter (mean decrease 1.7 mm; 95% CI 0.9 to 2.6; p<0.001), and in the number of pain episodes/year (mean decrease, 3.7; 95% CI 2.6 to 4.9; p<0.001). Treatment costs per patient were three times higher in the ESWL combined with endoscopy group compared with the ESWL alone group (p = 0.001). The median delay between the onset of chronic pancreatitis and persistent pain relief for both groups was 1.1 year (95% CI 0.7 to 1.6), as compared with 4 years (95% CI 3 to 4) for the natural history of chronic pancreatitis in a reference cohort (p<0.001). CONCLUSIONS ESWL is a safe and effective preferred treatment for selected patients with painful calcified chronic pancreatitis. Combining systematic endoscopy with ESWL adds to the cost of patient care, without improving the outcome of pancreatic pain.", "author" : [ { "dropping-particle" : "", "family" : "Dumonceau", "given" : "Jean-Marc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Costamagna", "given" : "Guido", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tringali", "given" : "Andrea", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vahedi", "given" : "Kouroche", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delhaye", "given" : "Myriam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hittelet", "given" : "Axel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spera", "given" : "Gianluca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giostra", "given" : "Emiliano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mutignani", "given" : "Massimiliano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maertelaer", "given" : "Viviane", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devi\u00e8re", "given" : "Jacques", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gut", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2007", "4", "1" ] ] }, "note" : "NULL", "page" : "545-52", "title" : "Treatment for painful calcified chronic pancreatitis: extracorporeal shock wave lithotripsy versus endoscopic treatment: a randomised controlled trial.", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(261)", "plainTextFormattedCitation" : "(261)", "previouslyFormattedCitation" : "(261)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(261)Prospective randomized controlled trial29 patients72% men, 69% OHAge: 49 yDuration of disease: --Severe CP: 100%Pain: 100%(Type A: 66%)FU: 4.2 yDiabetes: 14%Steatorrhea: --ESWL: n=29Pancreatic stenting: 13/29 = 45%Technical success: NAPain relief assessment:- VAS (intensity)- number of pain episodes/yComplete pain relief At 2 y: 55%: 16/29 At 4.2 y: 55%: 16/29Need for ERCP: 18/29 = 62%Need for ESWL: 7/29 = 24%Need for surgery: 3/29 = 10%Factor independently associated with absence of pain relapse (whole series)-Location of obstructive calcification in the head of pancreas (p=0.013)Treatment costs per patient 3 times higher in the group ESWL + endoscopy compared to ESWL aloneLOE: highHirota (2011)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/MPA.0b013e31821a9215", "ISSN" : "1536-4828", "PMID" : "21747315", "abstract" : "OBJECTIVES The aim of this study was to compare the benefits between endoscopic drainage and surgical drainage of the pancreatic duct for patients with chronic calcified pancreatitis. METHODS A total of 68 patients were classified into endoscopic (n = 34) or surgical (n = 34) treatment groups. Patients receiving endoscopic treatment were further divided into 2 subgroups: a short-period group, patients who could discontinue serial pancreatic stenting within 1 year (n = 19); and a long-period group, patients who needed pancreatic drainage by serial endoscopic stenting for more than 1 year (n = 15). The medical records of these patients were retrospectively analyzed. RESULTS Hospital stays, frequency of hospitalizations, and medical expense were similar between the short-period endoscopic treatment group and surgery group. On the other hand, patients in the long-period endoscopic treatment group required significantly longer hospital stays, more frequent hospitalizations, and had higher medical expenses than the short-period endoscopic treatment group as well as than the surgery group. CONCLUSIONS Patients who underwent serial endoscopic stenting for more than 1 year showed no benefit compared with surgical treatment in terms of the frequency of hospital stays and medical costs.", "author" : [ { "dropping-particle" : "", "family" : "Hirota", "given" : "Morihisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Asakura", "given" : "Tohru", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kanno", "given" : "Atsushi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kikuta", "given" : "Kazuhiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kume", "given" : "Kiyoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hamada", "given" : "Shin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Unno", "given" : "Jun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ito", "given" : "Hiromichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ariga", "given" : "Hiroyuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Masamune", "given" : "Atsushi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Satoh", "given" : "Kennichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Motoi", "given" : "Fuyuhiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Egawa", "given" : "Shinichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Unno", "given" : "Michiaki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shimosegawa", "given" : "Tooru", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreas", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2011", "8" ] ] }, "note" : "NULL", "page" : "946-50", "title" : "Long-period pancreatic stenting for painful chronic calcified pancreatitis required higher medical costs and frequent hospitalizations compared with surgery.", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(274)", "plainTextFormattedCitation" : "(274)", "previouslyFormattedCitation" : "(274)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(274)Retrospective34 patients74% men, 50% OHAge: 54.8 yDuration of disease: --Severe CP: 100%Pain: 100%FU: 3.4 yDiabetes: --Steatorrhea: --EPSESWL (n=21)Pancreatic stenting (n=34)Duration of pancreatic stenting 3.2 m (n=19) 27.0 m (n=15)Pain relief assessment: NAIncidence rate of pain (AP) 0.21 (n=34) 0.11 (n=19) 0.37 (n=15)Surgery: 6/34 = 18%LOE: lowSeven (2012)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.gie.2012.01.014", "ISSN" : "1097-6779", "PMID" : "22401819", "abstract" : "BACKGROUND Most outcomes data on pancreatic extracorporeal shock wave lithotripsy (P-ESWL) for chronic calcific pancreatitis (CCP) are based on studies with <4 years' follow-up, and U.S. long-term studies are lacking. OBJECTIVE To report long-term P-ESWL outcomes for CCP and to assess whether smoking or alcohol use influences P-ESWL outcomes. DESIGN Cross-sectional study, retrospective chart review. SETTING Virginia Mason Medical Center, Seattle, Washington. PATIENTS This study involved 120 patients who underwent P-ESWL and ERCP for CCP and completed an outcomes questionnaire. INTERVENTION P-ESWL and ERCP, outcomes survey. MAIN OUTCOME MEASUREMENTS Pain, quality of life, narcotics use, diabetes status, pancreatic enzyme requirement, repeat P-ESWL, repeat ERCP, surgery. RESULTS A total of 120 patients underwent P-ESWL followed by ERCP (mean \u00b1 standard deviation [SD] follow-up 4.3 [\u00b1 3.7] years) and completed a survey. The mean (\u00b1 SD) before-P-ESWL pain score was 7.9 (\u00b1 2.6) compared with 2.9 (\u00b1 2.6) after P-ESWL (P < .001). Improved pain was reported by 102 patients (85%); 60 (50%) reported complete pain relief and no narcotic use. The mean (\u00b1 SD) before-P-ESWL quality-of-life score was 3.7 (\u00b1 2.4) compared with 7.3 (\u00b1 2.7) after P-ESWL (P < .001). In patients with \u2265 4 years' follow-up, repeat procedures included P-ESWL (29%), ERCP (84%), and surgery (16%). Smokers who quit smoking after P-ESWL had improved narcotic requirements compared with those who continued smoking (95% vs 67%; P = .014), and a trend suggested a decreased need for repeat ERCPs (68% vs 84%; P = .071). LIMITATIONS Single center, retrospective, recall bias, nonvalidated pain and quality-of-life scales. CONCLUSION P-ESWL as the initial therapy for CCP may lead to more lifetime procedures; however, partial pain relief in 85%, complete pain relief with no narcotic use in 50%, and avoidance of surgery in 84% of patients may be achieved. Quitting smoking after P-ESWL may improve outcomes.", "author" : [ { "dropping-particle" : "", "family" : "Seven", "given" : "Gulseren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schreiner", "given" : "Mitchal A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ross", "given" : "Andrew S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lin", "given" : "Otto S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gluck", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gan", "given" : "S Ian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Irani", "given" : "Shayan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brandabur", "given" : "John J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Patterson", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuhr", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kozarek", "given" : "Richard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastrointestinal endoscopy", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2012", "5" ] ] }, "note" : "NULL", "page" : "997-1004.e1", "title" : "Long-term outcomes associated with pancreatic extracorporeal shock wave lithotripsy for chronic calcific pancreatitis.", "type" : "article-journal", "volume" : "75" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(256)", "plainTextFormattedCitation" : "(256)", "previouslyFormattedCitation" : "(256)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(256)Retrospective cross-sectional study120 patients43% men, 54% OHAge: 52 yDuration of disease (n=215): 63 mSevere CP: --Pain: 100%FU: 4.3 yDiabetes: 18%Steatorrhea: 53%EPS (n=120)ESWL (n=120)Pancreatic stenting (114/120 = 95%)Technical success: NAPain relief assessment VAS (1 – 10) narcotic medicationComplete pain relief: 60/12 = 50%Partial pain relief: 42/120 = 35%Complete or partial pain relief: 85% narcotic medication: 69/91 = 76%Stop narcotic medication: 58%FU 4 y (n=55) (mean FU: 7.5 y)Need for ESWL: 16/55 = 29%Need for ERCP: 46/55 = 84%Need for surgery: 9/55 = 16%Factors predicting improvement in narcotic pain medication useSmokers who quit smoking after ESWL (95% vs 67%, p=0.014)LOE: moderateSuzuki (2013)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/MPA.0b013e31827308c8", "ISSN" : "1536-4828", "PMID" : "23558239", "abstract" : "OBJECTIVES A Japanese multicenter study of pancreatolithiasis was performed to investigate its clinical features and determine treatment strategies for pancreatolithiasis. METHODS A retrospective study was performed on 916 patients managed in 34 institutions for a period of more than 5 years. RESULTS The treatment methods were extracorporeal shock wave lithotripsy (ESWL) in 479 patients, surgery in 133, and endoscopy alone in 68. Fragmentation of stones after ESWL was achieved in 92.4% of the patients. However, complete stone clearance was achieved in 49.4% of the patients after ESWL alone. The complete stone clearance rate was lower after ESWL than after endoscopy (87.9%). The incidence of early complications was significantly higher after surgery (13.3%) than after ESWL (6.1%). The frequencies of total stone recurrence after ESWL (22.5%) and endoscopy (12.0%) were significantly higher than that after surgery (1.5%). After ESWL (17.6%), abdominal pain recurred significantly more frequently than after surgery (2.2%). Stones and abdominal pain most often recurred within 3 years after ESWL and endoscopy. CONCLUSIONS First-line treatment of pancreatic stones should be ESWL alone or with endoscopy because of its minimal invasiveness and low incidence of early complications. Surgery should be performed on patients in whom ESWL and endoscopy failed.", "author" : [ { "dropping-particle" : "", "family" : "Suzuki", "given" : "Yutaka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sugiyama", "given" : "Masanori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Inui", "given" : "Kazuo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Igarashi", "given" : "Yoshinori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ohara", "given" : "Hirotaka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tazuma", "given" : "Susumu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsuji", "given" : "Tadao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyakawa", "given" : "Hiroyuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atomi", "given" : "Yutaka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreas", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2013", "5" ] ] }, "note" : "NULL", "page" : "584-8", "title" : "Management for pancreatolithiasis: a Japanese multicenter study.", "type" : "article-journal", "volume" : "42" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(264)", "plainTextFormattedCitation" : "(264)", "previouslyFormattedCitation" : "(264)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(264)Retrospective multicenter: 34 centers916 patients86% men, 74% OHAge: --Duration of disease: --Severe CP: --Pain: --FU: 3.5 yDiabetes: --Steatorrhea: --ESWL (n=457)Endoscopy alone (n=83)ESWL alone (n=202)Surgery (n=135)Complete MPD clearance: 74%Pain relief assessment: NAEarly complete or partial pain relief After ESWL: 91% After endoscopy: 96% After surgery: 99%Recurrent pain (most frequently within 3 y) After ESWL: 18% After endoscopy: 8% After surgery: 5%Need for surgery after ESWL/endoscopy: 10/540 = 1.9%LOE: lowTandam (2013)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.gie.2013.05.012", "ISSN" : "1097-6779", "PMID" : "23891416", "abstract" : "BACKGROUND Long-term results of extracorporeal shockwave lithotripsy (ESWL) for large pancreatic duct (PD) stones in patients with idiopathic calcific pancreatitis (CP) are scanty. OBJECTIVE To evaluate intermediate and long-term results of ESWL in a large cohort of patients with idiopathic CP. DESIGN Cross-sectional study; retrospective chart review. SETTING A high-volume, tertiary-care center for endoscopy and GI diseases. PATIENTS A total of 636 patients with idiopathic CP who underwent ESWL and ERCP were followed-up. Patients were divided into intermediate (24-60 months) and long-term (>60 months) follow-up groups. INTERVENTION ESWL and ERCP. MAIN OUTCOME MEASUREMENTS Improvement in pain, analgesic use, hospitalization for pain, recurrence of calculi, need for additional intervention, and quality of life. RESULTS A total of 636 of 1006 patients who underwent ESWL between 2004 and 2009 were followed for a maximum of 96 months. There were 364 patients in the intermediate follow-up group and 272 in the long-term follow-up group. After ESWL and ERCP, absence of pain was seen in 250 patients (68.7%), mild-to-moderate pain in 94 patients (25.4%), and severe pain in 20 patients (5.5%) of the intermediate group. In the long-term group, 164 patients (60.3%) had no pain, 97 patients (35.7%) had mild or moderate episodes of pain, whereas 11 patients (4.04%) had episodic severe pain. Recurrence of calculi was seen in 51 patients (14.01%) in the intermediate follow-up group and in 62 patients (22.8%) in the long-term group. Quality of life improved in a significant number of patients in both groups. LIMITATIONS Retrospective study, single center, recall bias, and subjective pain and quality-of-life measurement scale. CONCLUSION ESWL for large PD calculi offers good results in patients of idiopathic CP on intermediate and long-term follow-up.", "author" : [ { "dropping-particle" : "", "family" : "Tandan", "given" : "Manu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reddy", "given" : "Duvvur Nageshwar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Talukdar", "given" : "Rupjyoti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vinod", "given" : "Koppuju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Santosh", "given" : "Darisetty", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lakhtakia", "given" : "Sundeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gupta", "given" : "Rajesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramchandani", "given" : "Mohan J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banerjee", "given" : "Rupa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rakesh", "given" : "Kalapala", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Varadaraj", "given" : "Gokak", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rao", "given" : "Guduru Venkat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastrointestinal endoscopy", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2013", "11" ] ] }, "note" : "NULL", "page" : "726-33", "title" : "Long-term clinical outcomes of extracorporeal shockwave lithotripsy in painful chronic calcific pancreatitis.", "type" : "article-journal", "volume" : "78" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(275)", "plainTextFormattedCitation" : "(275)", "previouslyFormattedCitation" : "(275)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(275)Retrospective analysis of a prospective database636 patients364 FU 2 – 5 y272 FU > 5 y65% men, 0% OHAge: --Duration of disease: --Severe CP: --Pain: 100%FU: 2 - 5 yDiabetes: 24%Steatorrhea: 8%EPS (n=636)ESWL (n=636)Pancreatic stenting: 347/636 = 55%Complete MPD clearance: 78%Technical success: 100% (complete or partial MPD clearance)Pain relief assessment- VAS score (0 – 10)- number of analgesics- hospitalizations for painComplete pain relief: 250/364 = 69%Partial pain relief: 93/364 = 26%Complete or partial pain relief: 94%Surgery: 56/636 = 9%LOE: moderateOhyama (2015)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/MPA.0000000000000277", "ISSN" : "1536-4828", "PMID" : "25438070", "abstract" : "OBJECTIVES Patients with chronic pancreatitis are managed by extracorporeal shock wave lithotripsy (ESWL) for pancreatic stones. Stone density on noncontrast computed tomography (NCCT) is used to predict stone composition and fragility, but no report investigating the pancreatic stone density has been documented. We aimed to assess the usefulness of pancreatic stone density on NCCT in predicting the ESWL outcome. METHODS We evaluated 128 consecutive patients with pancreatic stones who underwent ESWL. Pancreatic stone density on NCCT was measured in Hounsfield units. Patients with complete stone removal were compared with those with incomplete stone removal. Patient characteristics; imaging findings, including stone density; and interventions were evaluated as potential predictors. The optimal cutoff value of variables to differentiate complete removal from incomplete removal was determined by receiver operating characteristic analysis. RESULTS Complete stone removal was achieved in 66 patients (51.6%). When the density threshold was set at 820.5 Hounsfield units, complete stone removal was achieved in 52 patients (78.8%) with lower-density stones. In multivariate analysis, single stone (P = 0.007) and lower-density stone (P < 0.001) revealed significant association with complete stone removal. CONCLUSIONS The measurement of pancreatic stone density before therapy can help predict therapeutic outcomes.", "author" : [ { "dropping-particle" : "", "family" : "Ohyama", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mikata", "given" : "Rintaro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ishihara", "given" : "Takeshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsuyuguchi", "given" : "Toshio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sakai", "given" : "Yuji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sugiyama", "given" : "Harutoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yasui", "given" : "Shin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ishii", "given" : "Kiyofumi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Itoh", "given" : "Sadahiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nishikawa", "given" : "Takao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Yuto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yokosuka", "given" : "Osamu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreas", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2015", "4" ] ] }, "note" : "NULL", "page" : "422-8", "title" : "Efficacy of stone density on noncontrast computed tomography in predicting the outcome of extracorporeal shock wave lithotripsy for patients with pancreatic stones.", "type" : "article-journal", "volume" : "44" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(266)", "plainTextFormattedCitation" : "(266)", "previouslyFormattedCitation" : "(266)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(266)Consecutive case series128 patients77% men, 66% OHAge: 51.4 yDuration of disease: --Severe CP: --Pain: 100%FU: 3.5 yDiabetes: 22%Steatorrhea: --EPSESWLPancreatic stenting: 14/128 = 11%Duration of stenting: 1 yComplete MPD clearance: 66/128 = 52%Pain relief assessment4-grade scaleImmediate pain relief: 115/128 = 90%Pain relief in complete MPD clearance: 61/66 = 92%Pain relief in incomplete ductal clearance: 54/62 = 87%Surgery: 1/128 = 0.8%Pain relapse occurred at an early date in patients with incomplete duct clearance (39 m vs 84 m)LOE: lowTable 2S= ESWL + Endoscopy – Medium term FU 2 - 5 y – Studies 50 patientsAuthor (year) (ref)DesignNumber of patientsComplete or partial pain reliefFU (months)Comments (LOE)Adamek (1999)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0017-5749", "PMID" : "10446109", "abstract" : "BACKGROUND There have been conflicting reports as to whether pancreatic ductal drainage achieved by endoscopy and lithotripsy improves the clinical outcome of patients with chronic pancreatitis. AIMS To determine the clinical outcome in patients with chronic pancreatitis who received extracorporeal shock wave lithotripsy (ESWL), and were followed up for two to eight years. METHODS Eighty patients with severe chronic pancreatitis and endoscopically unretrievable obstructive stones underwent ESWL with a piezoelectric lithotripter between 1989 and 1996. Clinical status, relief of symptoms, further endoscopic or surgical interventions, and mortality were defined. RESULTS Forty three (54%) patients were treated successfully with ESWL. The only feature associated with treatment success was the presence of a single stone rather than multiple stones. Successfully treated patients tended to experience less pain, although this did not reach statistical significance. A slight increase in weight was noted in our patients; however, there was no notable improvement in anomalous stools and diabetes mellitus. Five patients died due to extrapancreatic reasons. No pancreatic carcinomas developed. CONCLUSIONS ESWL associated with endoscopic drainage is a safe technique that is particularly successful in patients with a single stone. However, pancreatic drainage by endoscopy and ESWL has almost no effect on pain in chronic pancreatitis. Furthermore, endoscopic management and ESWL does not prevent or postpone the development of glandular insufficiency.", "author" : [ { "dropping-particle" : "", "family" : "Adamek", "given" : "H E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jakobs", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buttmann", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adamek", "given" : "M U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schneider", "given" : "A R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Riemann", "given" : "J F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gut", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "1999", "9" ] ] }, "note" : "NULL", "page" : "402-5", "title" : "Long term follow up of patients with chronic pancreatitis and pancreatic stones treated with extracorporeal shock wave lithotripsy.", "type" : "article-journal", "volume" : "45" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(265)", "plainTextFormattedCitation" : "(265)", "previouslyFormattedCitation" : "(265)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(265) Retrospective8076% (61 / 80)Complete 54% (43 / 80)40--LOE: lowFarnbacher (2002)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1067/mge.2002.128162", "ISSN" : "0016-5107", "PMID" : "12297764", "abstract" : "BACKGROUND The aim of the study was to evaluate interventional endoscopic management of pancreatic duct stones in patients with chronic pancreatitis by describing therapeutic methods and defining factors that predict technical success. METHODS Records were retrospectively analyzed for 125 patients with symptoms caused by chronic pancreatitis with pancreatic duct stones (single 43, multiple 82) treated by interventional endoscopy, including extracorporeal shockwave lithotripsy. RESULTS Technical success was achieved in 85% of patients (11 patients by mechanical lithotripsy, 114 by piezoelectric extracorporeal shockwave lithotripsy). There were no serious complications from lithotripsy. Univariate analysis disclosed a statistically significant association between treatment success and patient age as well as prepapillary location of stones. A greater therapeutic effort was necessary in patients with stones located in the tail of the pancreas, 2 or more stones, a stone 12 mm or more in diameter, or who have had a longer duration (>8 years) of the disease. However, with exception of the last parameter, correction for multiple testing of data removed statistical significance. CONCLUSIONS Extracorporeal shockwave lithotripsy enhances endoscopic measures for treatment of pancreatic duct stones when mechanical lithotripsy fails. Middle-aged patients in the early stages of chronic pancreatitis with stones in a prepapillary location proved to be the best candidates for successful treatment. Unfavorable patient-related or morphologic factors can be compensated for through more intense efforts at therapy.", "author" : [ { "dropping-particle" : "", "family" : "Farnbacher", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schoen", "given" : "Christoph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rabenstein", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benninger", "given" : "Johannes", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hahn", "given" : "Eckhart G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schneider", "given" : "H Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastrointestinal endoscopy", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2002", "10" ] ] }, "note" : "NULL", "page" : "501-6", "title" : "Pancreatic duct stones in chronic pancreatitis: criteria for treatment intensity and success.", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(235)", "plainTextFormattedCitation" : "(235)", "previouslyFormattedCitation" : "(235)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(235) Retrospective125Complete: 48% (40 / 84)ITT: 40 / 125 = 32%29--LOE: lowInui (2005)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1536-4828", "PMID" : "15632696", "abstract" : "OBJECTIVES A retrospective multicenter survey was performed to evaluate the efficacy of extracorporeal shock wave lithotripsy (ESWL) as a treatment of pancreatic stones. METHODS A survey was sent to 11 institutions belonging to the Japanese Association of Extracorporeal Shock Wave Lithotripsy in Digestive Diseases, and data were collected on 555 patients who underwent ESWL for pancreatic stones between January 1990 and September 2002. The male:female ratio was 5.2:1, and the mean age was 52.5 years. The etiology was alcohol related in 425 patients (76.6%) and idiopathic in 111 patients (20.0%); 204 patients (36.8%) had a single stone and 470 patients (84.7%) were symptomatic. RESULTS Mean frequency of the procedure was 5.0 times (range, 1-29). Fragmentation of stones was achieved in 513 patients (92.4%), and the complete stone clearance rate after ESWL alone or in combination with interventional endoscopy was 72.6%. Symptom relief was achieved in 428 (91.1%) of 470 patients. Thirty-five patients (6.3%) developed complications, including 30 patients (5.4%) who developed acute pancreatitis. Five hundred four (90.8%) patients were followed for a mean of 44.3 months, during which 122 (22.0%) suffered stone recurrence (mean time to recurrence, 25.1 months). Twenty-two (4.1%) of the 504 patients who were followed required surgery. Pancreatic exocrine function improved in 65 patients (38.0%), was unchanged in 49 patients (28.7%), and progressed in 57 patients (33.3%). Pancreatic endocrine function improved in 44 patients (24.3%), was unchanged in 85 patients (47.0%), and progressed in 52 patients (28.7%). CONCLUSION ESWL is the treatment of choice for clearing pancreatic stones.", "author" : [ { "dropping-particle" : "", "family" : "Inui", "given" : "Kazuo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tazuma", "given" : "Susumu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamaguchi", "given" : "Taketo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ohara", "given" : "Hirotaka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsuji", "given" : "Tadao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyagawa", "given" : "Hiroyuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Igarashi", "given" : "Yoshinori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakamura", "given" : "Yuta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atomi", "given" : "Yutaka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreas", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2005", "1" ] ] }, "note" : "NULL", "page" : "26-30", "title" : "Treatment of pancreatic stones with extracorporeal shock wave lithotripsy: results of a multicenter survey.", "type" : "article-journal", "volume" : "30" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(263)", "plainTextFormattedCitation" : "(263)", "previouslyFormattedCitation" : "(263)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(263) Retrospective55576% (382 / 504)ITT: 382 / 555 = 69%44LOE: lowSeven (2012) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.gie.2012.01.014", "ISSN" : "1097-6779", "PMID" : "22401819", "abstract" : "BACKGROUND Most outcomes data on pancreatic extracorporeal shock wave lithotripsy (P-ESWL) for chronic calcific pancreatitis (CCP) are based on studies with <4 years' follow-up, and U.S. long-term studies are lacking. OBJECTIVE To report long-term P-ESWL outcomes for CCP and to assess whether smoking or alcohol use influences P-ESWL outcomes. DESIGN Cross-sectional study, retrospective chart review. SETTING Virginia Mason Medical Center, Seattle, Washington. PATIENTS This study involved 120 patients who underwent P-ESWL and ERCP for CCP and completed an outcomes questionnaire. INTERVENTION P-ESWL and ERCP, outcomes survey. MAIN OUTCOME MEASUREMENTS Pain, quality of life, narcotics use, diabetes status, pancreatic enzyme requirement, repeat P-ESWL, repeat ERCP, surgery. RESULTS A total of 120 patients underwent P-ESWL followed by ERCP (mean \u00b1 standard deviation [SD] follow-up 4.3 [\u00b1 3.7] years) and completed a survey. The mean (\u00b1 SD) before-P-ESWL pain score was 7.9 (\u00b1 2.6) compared with 2.9 (\u00b1 2.6) after P-ESWL (P < .001). Improved pain was reported by 102 patients (85%); 60 (50%) reported complete pain relief and no narcotic use. The mean (\u00b1 SD) before-P-ESWL quality-of-life score was 3.7 (\u00b1 2.4) compared with 7.3 (\u00b1 2.7) after P-ESWL (P < .001). In patients with \u2265 4 years' follow-up, repeat procedures included P-ESWL (29%), ERCP (84%), and surgery (16%). Smokers who quit smoking after P-ESWL had improved narcotic requirements compared with those who continued smoking (95% vs 67%; P = .014), and a trend suggested a decreased need for repeat ERCPs (68% vs 84%; P = .071). LIMITATIONS Single center, retrospective, recall bias, nonvalidated pain and quality-of-life scales. CONCLUSION P-ESWL as the initial therapy for CCP may lead to more lifetime procedures; however, partial pain relief in 85%, complete pain relief with no narcotic use in 50%, and avoidance of surgery in 84% of patients may be achieved. Quitting smoking after P-ESWL may improve outcomes.", "author" : [ { "dropping-particle" : "", "family" : "Seven", "given" : "Gulseren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schreiner", "given" : "Mitchal A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ross", "given" : "Andrew S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lin", "given" : "Otto S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gluck", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gan", "given" : "S Ian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Irani", "given" : "Shayan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brandabur", "given" : "John J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Patterson", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuhr", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kozarek", "given" : "Richard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastrointestinal endoscopy", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2012", "5" ] ] }, "note" : "NULL", "page" : "997-1004.e1", "title" : "Long-term outcomes associated with pancreatic extracorporeal shock wave lithotripsy for chronic calcific pancreatitis.", "type" : "article-journal", "volume" : "75" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(256)", "plainTextFormattedCitation" : "(256)", "previouslyFormattedCitation" : "(256)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(256)Retrospective12085% (102 / 120)Complete: 50% (60 / 120)52Factors predicting improvement in narcotic pain medication useSmokers who quit smokingLOE: moderateSuzuki (2013)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/MPA.0b013e31827308c8", "ISSN" : "1536-4828", "PMID" : "23558239", "abstract" : "OBJECTIVES A Japanese multicenter study of pancreatolithiasis was performed to investigate its clinical features and determine treatment strategies for pancreatolithiasis. METHODS A retrospective study was performed on 916 patients managed in 34 institutions for a period of more than 5 years. RESULTS The treatment methods were extracorporeal shock wave lithotripsy (ESWL) in 479 patients, surgery in 133, and endoscopy alone in 68. Fragmentation of stones after ESWL was achieved in 92.4% of the patients. However, complete stone clearance was achieved in 49.4% of the patients after ESWL alone. The complete stone clearance rate was lower after ESWL than after endoscopy (87.9%). The incidence of early complications was significantly higher after surgery (13.3%) than after ESWL (6.1%). The frequencies of total stone recurrence after ESWL (22.5%) and endoscopy (12.0%) were significantly higher than that after surgery (1.5%). After ESWL (17.6%), abdominal pain recurred significantly more frequently than after surgery (2.2%). Stones and abdominal pain most often recurred within 3 years after ESWL and endoscopy. CONCLUSIONS First-line treatment of pancreatic stones should be ESWL alone or with endoscopy because of its minimal invasiveness and low incidence of early complications. Surgery should be performed on patients in whom ESWL and endoscopy failed.", "author" : [ { "dropping-particle" : "", "family" : "Suzuki", "given" : "Yutaka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sugiyama", "given" : "Masanori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Inui", "given" : "Kazuo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Igarashi", "given" : "Yoshinori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ohara", "given" : "Hirotaka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tazuma", "given" : "Susumu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsuji", "given" : "Tadao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyakawa", "given" : "Hiroyuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atomi", "given" : "Yutaka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreas", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2013", "5" ] ] }, "note" : "NULL", "page" : "584-8", "title" : "Management for pancreatolithiasis: a Japanese multicenter study.", "type" : "article-journal", "volume" : "42" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(264)", "plainTextFormattedCitation" : "(264)", "previouslyFormattedCitation" : "(264)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(264) Retrospective916After ESWL: 91%After Endoscopy: 96%42LOE: lowTandan (2013)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.gie.2013.05.012", "ISSN" : "1097-6779", "PMID" : "23891416", "abstract" : "BACKGROUND Long-term results of extracorporeal shockwave lithotripsy (ESWL) for large pancreatic duct (PD) stones in patients with idiopathic calcific pancreatitis (CP) are scanty. OBJECTIVE To evaluate intermediate and long-term results of ESWL in a large cohort of patients with idiopathic CP. DESIGN Cross-sectional study; retrospective chart review. SETTING A high-volume, tertiary-care center for endoscopy and GI diseases. PATIENTS A total of 636 patients with idiopathic CP who underwent ESWL and ERCP were followed-up. Patients were divided into intermediate (24-60 months) and long-term (>60 months) follow-up groups. INTERVENTION ESWL and ERCP. MAIN OUTCOME MEASUREMENTS Improvement in pain, analgesic use, hospitalization for pain, recurrence of calculi, need for additional intervention, and quality of life. RESULTS A total of 636 of 1006 patients who underwent ESWL between 2004 and 2009 were followed for a maximum of 96 months. There were 364 patients in the intermediate follow-up group and 272 in the long-term follow-up group. After ESWL and ERCP, absence of pain was seen in 250 patients (68.7%), mild-to-moderate pain in 94 patients (25.4%), and severe pain in 20 patients (5.5%) of the intermediate group. In the long-term group, 164 patients (60.3%) had no pain, 97 patients (35.7%) had mild or moderate episodes of pain, whereas 11 patients (4.04%) had episodic severe pain. Recurrence of calculi was seen in 51 patients (14.01%) in the intermediate follow-up group and in 62 patients (22.8%) in the long-term group. Quality of life improved in a significant number of patients in both groups. LIMITATIONS Retrospective study, single center, recall bias, and subjective pain and quality-of-life measurement scale. CONCLUSION ESWL for large PD calculi offers good results in patients of idiopathic CP on intermediate and long-term follow-up.", "author" : [ { "dropping-particle" : "", "family" : "Tandan", "given" : "Manu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reddy", "given" : "Duvvur Nageshwar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Talukdar", "given" : "Rupjyoti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vinod", "given" : "Koppuju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Santosh", "given" : "Darisetty", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lakhtakia", "given" : "Sundeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gupta", "given" : "Rajesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramchandani", "given" : "Mohan J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banerjee", "given" : "Rupa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rakesh", "given" : "Kalapala", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Varadaraj", "given" : "Gokak", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rao", "given" : "Guduru Venkat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastrointestinal endoscopy", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2013", "11" ] ] }, "note" : "NULL", "page" : "726-33", "title" : "Long-term clinical outcomes of extracorporeal shockwave lithotripsy in painful chronic calcific pancreatitis.", "type" : "article-journal", "volume" : "78" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(275)", "plainTextFormattedCitation" : "(275)", "previouslyFormattedCitation" : "(275)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(275) Retrospective636N = 364; FU: 2 – 5 y94% (343 / 364)Complete: 69% (250 / 364)24 – 60LOE: moderateOhyama (2015)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/MPA.0000000000000277", "ISSN" : "1536-4828", "PMID" : "25438070", "abstract" : "OBJECTIVES Patients with chronic pancreatitis are managed by extracorporeal shock wave lithotripsy (ESWL) for pancreatic stones. Stone density on noncontrast computed tomography (NCCT) is used to predict stone composition and fragility, but no report investigating the pancreatic stone density has been documented. We aimed to assess the usefulness of pancreatic stone density on NCCT in predicting the ESWL outcome. METHODS We evaluated 128 consecutive patients with pancreatic stones who underwent ESWL. Pancreatic stone density on NCCT was measured in Hounsfield units. Patients with complete stone removal were compared with those with incomplete stone removal. Patient characteristics; imaging findings, including stone density; and interventions were evaluated as potential predictors. The optimal cutoff value of variables to differentiate complete removal from incomplete removal was determined by receiver operating characteristic analysis. RESULTS Complete stone removal was achieved in 66 patients (51.6%). When the density threshold was set at 820.5 Hounsfield units, complete stone removal was achieved in 52 patients (78.8%) with lower-density stones. In multivariate analysis, single stone (P = 0.007) and lower-density stone (P < 0.001) revealed significant association with complete stone removal. CONCLUSIONS The measurement of pancreatic stone density before therapy can help predict therapeutic outcomes.", "author" : [ { "dropping-particle" : "", "family" : "Ohyama", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mikata", "given" : "Rintaro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ishihara", "given" : "Takeshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsuyuguchi", "given" : "Toshio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sakai", "given" : "Yuji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sugiyama", "given" : "Harutoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yasui", "given" : "Shin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ishii", "given" : "Kiyofumi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Itoh", "given" : "Sadahiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nishikawa", "given" : "Takao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Yuto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yokosuka", "given" : "Osamu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreas", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2015", "4" ] ] }, "note" : "NULL", "page" : "422-8", "title" : "Efficacy of stone density on noncontrast computed tomography in predicting the outcome of extracorporeal shock wave lithotripsy for patients with pancreatic stones.", "type" : "article-journal", "volume" : "44" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(266)", "plainTextFormattedCitation" : "(266)", "previouslyFormattedCitation" : "(266)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(266) Prospective128Immediate pain relief: 90% (115 / 128)42Pain relapse occurred at an early date in patients with incomplete duct clearanceLOE: lowTotal2288Complete: 48 – 69%Complete or partial: 76 – 94%Table 3 : ESWL + Endoscopy – Long term FU > 5 yAuthor (year) (ref)DesignPopulationInterventionOutcomeCommentsDelhaye (2004)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1542-3565", "PMID" : "15625655", "abstract" : "BACKGROUND & AIMS Endotherapy for patients with painful chronic pancreatitis (CP) gives early and midterm clinical results comparable with those of conventional surgery. The authors evaluated long-term clinical outcome after endoscopic pancreatic ductal drainage, focusing on pain and pancreatic endocrine/exocrine functions. METHODS Of 110 patients with painful CP endoscopically treated between October 1987 and December 1989, 56 long-surviving patients were followed-up for 14.4 years (SD, .6 y); 40 patients died and 14 patients were lost to follow-up evaluation. Technical results included decreased ductal dilation and stone clearance. Clinical results included the rate of hospitalizations for pain before and after endotherapy, the need for surgery, the course of endocrine/exocrine insufficiencies, and late mortality. RESULTS Complete or partial technical success initially was obtained in 48 of 56 long-surviving patients. Long-term clinical success (< or =5 hospitalizations for pain during follow-up evaluation, without surgery) was obtained for 37 of 56 patients. At a mean follow-up time of 14.4 years, 44 patients had avoided surgery and the annual rate of hospitalizations for pain decreased significantly (before endotherapy: 0.98 [+/-1.36] vs 0.40 [+/-0.51] for the 3 years thereafter vs 0.14 [+/-0.22] for the last 11 years of follow-up evaluation; P < .001). Short duration of disease before initial therapy and absence of smoking at the last follow-up evaluation were associated with long-term clinical success. CONCLUSIONS Endotherapy provides long-term benefits for about two thirds of patients with painful CP. Good clinical outcome was associated with cessation or absence of smoking, whereas alcohol abuse increased the risks for diabetes mellitus, steatorrhea, and mortality.", "author" : [ { "dropping-particle" : "", "family" : "Delhaye", "given" : "Myriam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arvanitakis", "given" : "Marianna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Verset", "given" : "Gontran", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cremer", "given" : "Michel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devi\u00e8re", "given" : "Jacques", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2004", "12" ] ] }, "note" : "NULL", "page" : "1096-106", "title" : "Long-term clinical outcome after endoscopic pancreatic ductal drainage for patients with painful chronic pancreatitis.", "type" : "article-journal", "volume" : "2" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(255)", "plainTextFormattedCitation" : "(255)", "previouslyFormattedCitation" : "(255)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(255)Retrospective56 patients:82% men, 68% OHAge: 44 yDuration of disease: 5 ySevere CP: 100%Pain: 100%(Type A: 55%)FU: 14.4 yDiabetes: 29%Steatorrhea: 29%EPS: n=56ESWL: n=56Pancreating stenting: 48%Technical success: 86%(complete or partial MPD clearance + MPD )ET completed: 61%Mean treatment duration: 28.7 mET ongoing: 18%Pain relief assessment number of hospitalizations for pain during FUComplete clinical success(no hospitalization): 17/56 = 30%Partial clinical success(1 – 5 hospitalisation): 20/56 = 36%Complete or partial clinical success: 66%Surgery: 12/56 = 21%Long-term clinical success associated with:shorter duration of disease before ETabsence of ongoing smokingshorter duration of ETlower number of ERCP proceduresLOE?: lowTadenuma (2005)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1542-3565", "PMID" : "16271345", "abstract" : "BACKGROUND & AIMS The aim of this study was to evaluate the short- and long-term results of extracorporeal shockwave lithotripsy (ESWL) and endoscopic therapy for pancreatic stones. METHODS A total of 117 patients with pancreatic stones underwent ESWL and endoscopic treatment in our institute. Seventy patients who were followed-up for over 3 years after treatment were evaluated retrospectively. RESULTS Immediate pain relief was achieved in 97% and complete removal of stones was achieved in 56%. During the long-term follow-up evaluation, 49 of 70 patients continued to be asymptomatic. Pain recurred more frequently in patients with incomplete removal than in those with complete removal (P < .05). Twenty-one patients who became symptomatic during the follow-up period underwent additional therapy, and pain relief was attained without surgery in all of them. Both endocrine and exocrine function deteriorated after the long-term follow-up period (P < .05). CONCLUSIONS ESWL and endoscopic treatment of pancreatic stones proved to be effective for long-term pain relief, especially in patients in whom stones were removed completely at initial therapy.", "author" : [ { "dropping-particle" : "", "family" : "Tadenuma", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ishihara", "given" : "Takeshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamaguchi", "given" : "Taketo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsuchiya", "given" : "Shouichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kobayashi", "given" : "Akitoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakamura", "given" : "Kazuyoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sakurada", "given" : "Reiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saisho", "given" : "Hiromitsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2005", "11" ] ] }, "note" : "NULL", "page" : "1128-35", "title" : "Long-term results of extracorporeal shockwave lithotripsy and endoscopic therapy for pancreatic stones.", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(234)", "plainTextFormattedCitation" : "(234)", "previouslyFormattedCitation" : "(234)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(234)Retrospective117 patients:73% men, 68% OHAge: 48 yDuration of disease: --Severe CP: --Pain: 100%FU (n=70): 77.5 mDiabetes: 36% (25/70)Steatorrhea: --ESWL (n=117)Endoscopy (n=65)Complete MPD clearance: 65/117 = 56%Pain relief assessment4-grade scale: none, mild, moderate, severePain relief (none or mild): 49/70 = 70% At 3 y after ET: 57/70 = 81% At 5 y after ET: 35/42 = 83% At 10 y after ET: 13/13 = 100%Surgery: 1/70 = 1.4%Prognostic factors for pain relapseIncomplete MPD stones removal after initial ET; HR 3.7, p=0.0067MPD stricture; HR 3.4, p=0.018LOE?: lowCahen (2011)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1053/j.gastro.2011.07.049", "ISSN" : "1528-0012", "PMID" : "21843494", "abstract" : "BACKGROUND & AIMS A randomized trial that compared endoscopic and surgical drainage of the pancreatic duct in patients with advanced chronic pancreatitis reported a significant benefit of surgery after a 2-year follow-up period. We evaluated the long-term outcome of these patients after 5 years. METHODS Between 2000 and 2004, 39 symptomatic patients were randomly assigned to groups that underwent endoscopic drainage or operative pancreaticojejunostomy. In 2009, information was collected regarding pain, quality of life, morbidity, mortality, length of hospital stay, number of procedures undergone, changes in pancreatic function, and costs. Analysis was performed according to an intention-to-treat principle. RESULTS During the 79-month follow-up period, one patient was lost and 7 died from unrelated causes. Of the patients treated by endoscopy, 68% required additional drainage compared with 5% in the surgery group (P = .001). Hospital stay and costs were comparable, but overall, patients assigned to endoscopy underwent more procedures (median, 12 vs 4; P = .001). Moreover, 47% of the patients in the endoscopy group eventually underwent surgery. Although the mean difference in Izbicki pain scores was no longer significant (39 vs 22; P = .12), surgery was still superior in terms of pain relief (80% vs 38%; P = .042). Levels of quality of life and pancreatic function were comparable. CONCLUSIONS In the long term, symptomatic patients with advanced chronic pancreatitis who underwent surgery as the initial treatment for pancreatic duct obstruction had more relief from pain, with fewer procedures, than patients who were treated endoscopically. Importantly, almost half of the patients who were treated with endoscopy eventually underwent surgery.", "author" : [ { "dropping-particle" : "", "family" : "Cahen", "given" : "Djuna L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gouma", "given" : "Dirk J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laram\u00e9e", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nio", "given" : "Yung", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rauws", "given" : "Erik A J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boermeester", "given" : "Marja A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Busch", "given" : "Olivier R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fockens", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuipers", "given" : "Ernst J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pereira", "given" : "Stephen P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wonderling", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dijkgraaf", "given" : "Marcel G W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruno", "given" : "Marco J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2011", "11" ] ] }, "note" : "NULL", "page" : "1690-5", "title" : "Long-term outcomes of endoscopic vs surgical drainage of the pancreatic duct in patients with chronic pancreatitis.", "type" : "article-journal", "volume" : "141" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(276)", "plainTextFormattedCitation" : "(276)", "previouslyFormattedCitation" : "(276)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(276)Prospective randomized controlled trial39 patients19 ET58% men, 37% OHAge: 52 yDuration of disease: 16 mSevere CP: 100%Pain: 100%(Type A: 37%)FU (n=16): 7.1 yDiabetes: 21%Steatorrhea: 68%19 ET / 20 surgeryAt 7.1 y 31 remaining patients (7 ?, 1 lost)16 ET / 15 surgeryESWL (16/19)Pancreating stenting (16/19)Median duration of stenting: 9.2 mPain relief assessmentIzbicki pain scoreComplete pain relief: 4/16 = 25%Partial pain relief: 2/16 = 13%Complete or partial pain relief: 6/16 = 38%Surgery: 9/19 = 47%Only 2/9 patients operated were completely free of pain after surgery (22%)This suggests that pain in these 7/16 patients (44%) was not related to MPD obstructionLOE?: highTandan (2013)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.gie.2013.05.012", "ISSN" : "1097-6779", "PMID" : "23891416", "abstract" : "BACKGROUND Long-term results of extracorporeal shockwave lithotripsy (ESWL) for large pancreatic duct (PD) stones in patients with idiopathic calcific pancreatitis (CP) are scanty. OBJECTIVE To evaluate intermediate and long-term results of ESWL in a large cohort of patients with idiopathic CP. DESIGN Cross-sectional study; retrospective chart review. SETTING A high-volume, tertiary-care center for endoscopy and GI diseases. PATIENTS A total of 636 patients with idiopathic CP who underwent ESWL and ERCP were followed-up. Patients were divided into intermediate (24-60 months) and long-term (>60 months) follow-up groups. INTERVENTION ESWL and ERCP. MAIN OUTCOME MEASUREMENTS Improvement in pain, analgesic use, hospitalization for pain, recurrence of calculi, need for additional intervention, and quality of life. RESULTS A total of 636 of 1006 patients who underwent ESWL between 2004 and 2009 were followed for a maximum of 96 months. There were 364 patients in the intermediate follow-up group and 272 in the long-term follow-up group. After ESWL and ERCP, absence of pain was seen in 250 patients (68.7%), mild-to-moderate pain in 94 patients (25.4%), and severe pain in 20 patients (5.5%) of the intermediate group. In the long-term group, 164 patients (60.3%) had no pain, 97 patients (35.7%) had mild or moderate episodes of pain, whereas 11 patients (4.04%) had episodic severe pain. Recurrence of calculi was seen in 51 patients (14.01%) in the intermediate follow-up group and in 62 patients (22.8%) in the long-term group. Quality of life improved in a significant number of patients in both groups. LIMITATIONS Retrospective study, single center, recall bias, and subjective pain and quality-of-life measurement scale. CONCLUSION ESWL for large PD calculi offers good results in patients of idiopathic CP on intermediate and long-term follow-up.", "author" : [ { "dropping-particle" : "", "family" : "Tandan", "given" : "Manu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reddy", "given" : "Duvvur Nageshwar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Talukdar", "given" : "Rupjyoti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vinod", "given" : "Koppuju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Santosh", "given" : "Darisetty", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lakhtakia", "given" : "Sundeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gupta", "given" : "Rajesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramchandani", "given" : "Mohan J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banerjee", "given" : "Rupa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rakesh", "given" : "Kalapala", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Varadaraj", "given" : "Gokak", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rao", "given" : "Guduru Venkat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastrointestinal endoscopy", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2013", "11" ] ] }, "note" : "NULL", "page" : "726-33", "title" : "Long-term clinical outcomes of extracorporeal shockwave lithotripsy in painful chronic calcific pancreatitis.", "type" : "article-journal", "volume" : "78" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(275)", "plainTextFormattedCitation" : "(275)", "previouslyFormattedCitation" : "(275)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(275)Retrospective analysis of a prospective database636 patients:272 FU > 5 y65% men, 0% OHAge: --Duration of disease: --Severe CP: --Pain: 100%Diabetes: 24%Steatorrhea: 8%EPS (n=636)ESWL (n=636)Pancreatic stenting: 370/636 = 58%Complete MPD clearance: 76%Technical success: 100% (complete or partial MPD clearance)Pain relief assessment- VAS score (0 – 10)- number of analgesics- hospitalization for painComplete pain relief: 60%Complete or partial pain relief: 96%Surgery: 56/636 = 9%LOE: moderateTable 3S= ESWL + Endoscopy – Long term FU > 5 y – Studies 50 patientsAuthor (year) (ref)DesignNumber of patientsComplete or partial pain reliefFU (months)Comments (LOE)Delhaye (2004)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1542-3565", "PMID" : "15625655", "abstract" : "BACKGROUND & AIMS Endotherapy for patients with painful chronic pancreatitis (CP) gives early and midterm clinical results comparable with those of conventional surgery. The authors evaluated long-term clinical outcome after endoscopic pancreatic ductal drainage, focusing on pain and pancreatic endocrine/exocrine functions. METHODS Of 110 patients with painful CP endoscopically treated between October 1987 and December 1989, 56 long-surviving patients were followed-up for 14.4 years (SD, .6 y); 40 patients died and 14 patients were lost to follow-up evaluation. Technical results included decreased ductal dilation and stone clearance. Clinical results included the rate of hospitalizations for pain before and after endotherapy, the need for surgery, the course of endocrine/exocrine insufficiencies, and late mortality. RESULTS Complete or partial technical success initially was obtained in 48 of 56 long-surviving patients. Long-term clinical success (< or =5 hospitalizations for pain during follow-up evaluation, without surgery) was obtained for 37 of 56 patients. At a mean follow-up time of 14.4 years, 44 patients had avoided surgery and the annual rate of hospitalizations for pain decreased significantly (before endotherapy: 0.98 [+/-1.36] vs 0.40 [+/-0.51] for the 3 years thereafter vs 0.14 [+/-0.22] for the last 11 years of follow-up evaluation; P < .001). Short duration of disease before initial therapy and absence of smoking at the last follow-up evaluation were associated with long-term clinical success. CONCLUSIONS Endotherapy provides long-term benefits for about two thirds of patients with painful CP. Good clinical outcome was associated with cessation or absence of smoking, whereas alcohol abuse increased the risks for diabetes mellitus, steatorrhea, and mortality.", "author" : [ { "dropping-particle" : "", "family" : "Delhaye", "given" : "Myriam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arvanitakis", "given" : "Marianna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Verset", "given" : "Gontran", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cremer", "given" : "Michel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devi\u00e8re", "given" : "Jacques", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2004", "12" ] ] }, "note" : "NULL", "page" : "1096-106", "title" : "Long-term clinical outcome after endoscopic pancreatic ductal drainage for patients with painful chronic pancreatitis.", "type" : "article-journal", "volume" : "2" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(255)", "plainTextFormattedCitation" : "(255)", "previouslyFormattedCitation" : "(255)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(255) Retrospective5666%Complete: 30%173Long-term clinical success associated withShorter duration of diseaseAbsence of ongoing smokingShorter duration of ETLower number of ERCP proceduresLOE: lowTadenuma (2005)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1542-3565", "PMID" : "16271345", "abstract" : "BACKGROUND & AIMS The aim of this study was to evaluate the short- and long-term results of extracorporeal shockwave lithotripsy (ESWL) and endoscopic therapy for pancreatic stones. METHODS A total of 117 patients with pancreatic stones underwent ESWL and endoscopic treatment in our institute. Seventy patients who were followed-up for over 3 years after treatment were evaluated retrospectively. RESULTS Immediate pain relief was achieved in 97% and complete removal of stones was achieved in 56%. During the long-term follow-up evaluation, 49 of 70 patients continued to be asymptomatic. Pain recurred more frequently in patients with incomplete removal than in those with complete removal (P < .05). Twenty-one patients who became symptomatic during the follow-up period underwent additional therapy, and pain relief was attained without surgery in all of them. Both endocrine and exocrine function deteriorated after the long-term follow-up period (P < .05). CONCLUSIONS ESWL and endoscopic treatment of pancreatic stones proved to be effective for long-term pain relief, especially in patients in whom stones were removed completely at initial therapy.", "author" : [ { "dropping-particle" : "", "family" : "Tadenuma", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ishihara", "given" : "Takeshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamaguchi", "given" : "Taketo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsuchiya", "given" : "Shouichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kobayashi", "given" : "Akitoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakamura", "given" : "Kazuyoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sakurada", "given" : "Reiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saisho", "given" : "Hiromitsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2005", "11" ] ] }, "note" : "NULL", "page" : "1128-35", "title" : "Long-term results of extracorporeal shockwave lithotripsy and endoscopic therapy for pancreatic stones.", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(234)", "plainTextFormattedCitation" : "(234)", "previouslyFormattedCitation" : "(234)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(234) Retrospective7070%78Prognostic factors of pain relapseIncomplete MPD clearanceMPD strictureLOE: moderateTandan (2013)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.gie.2013.05.012", "ISSN" : "1097-6779", "PMID" : "23891416", "abstract" : "BACKGROUND Long-term results of extracorporeal shockwave lithotripsy (ESWL) for large pancreatic duct (PD) stones in patients with idiopathic calcific pancreatitis (CP) are scanty. OBJECTIVE To evaluate intermediate and long-term results of ESWL in a large cohort of patients with idiopathic CP. DESIGN Cross-sectional study; retrospective chart review. SETTING A high-volume, tertiary-care center for endoscopy and GI diseases. PATIENTS A total of 636 patients with idiopathic CP who underwent ESWL and ERCP were followed-up. Patients were divided into intermediate (24-60 months) and long-term (>60 months) follow-up groups. INTERVENTION ESWL and ERCP. MAIN OUTCOME MEASUREMENTS Improvement in pain, analgesic use, hospitalization for pain, recurrence of calculi, need for additional intervention, and quality of life. RESULTS A total of 636 of 1006 patients who underwent ESWL between 2004 and 2009 were followed for a maximum of 96 months. There were 364 patients in the intermediate follow-up group and 272 in the long-term follow-up group. After ESWL and ERCP, absence of pain was seen in 250 patients (68.7%), mild-to-moderate pain in 94 patients (25.4%), and severe pain in 20 patients (5.5%) of the intermediate group. In the long-term group, 164 patients (60.3%) had no pain, 97 patients (35.7%) had mild or moderate episodes of pain, whereas 11 patients (4.04%) had episodic severe pain. Recurrence of calculi was seen in 51 patients (14.01%) in the intermediate follow-up group and in 62 patients (22.8%) in the long-term group. Quality of life improved in a significant number of patients in both groups. LIMITATIONS Retrospective study, single center, recall bias, and subjective pain and quality-of-life measurement scale. CONCLUSION ESWL for large PD calculi offers good results in patients of idiopathic CP on intermediate and long-term follow-up.", "author" : [ { "dropping-particle" : "", "family" : "Tandan", "given" : "Manu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reddy", "given" : "Duvvur Nageshwar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Talukdar", "given" : "Rupjyoti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vinod", "given" : "Koppuju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Santosh", "given" : "Darisetty", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lakhtakia", "given" : "Sundeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gupta", "given" : "Rajesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramchandani", "given" : "Mohan J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banerjee", "given" : "Rupa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rakesh", "given" : "Kalapala", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Varadaraj", "given" : "Gokak", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rao", "given" : "Guduru Venkat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastrointestinal endoscopy", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2013", "11" ] ] }, "note" : "NULL", "page" : "726-33", "title" : "Long-term clinical outcomes of extracorporeal shockwave lithotripsy in painful chronic calcific pancreatitis.", "type" : "article-journal", "volume" : "78" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(275)", "plainTextFormattedCitation" : "(275)", "previouslyFormattedCitation" : "(275)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(275) Retrospective27296%> 60LOE: moderateTotal39887% (66 – 96)Table 4 : Endoscopy “alone” (+ ESWL 60% of population) *with FU 24 mAuthor (year) (ref)DesignPopulationInterventionOutcomeCommentsBinmoeller* (1995)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1055/s-2007-1005780", "ISSN" : "0013-726X", "PMID" : "8903975", "abstract" : "BACKGROUND AND STUDY AIMS Endoscopic pancreatic stent drainage has been reported to relieve pain due to chronic pancreatitis in patients with ductal outflow obstruction. However, data regarding the long-term results, as presented here, have hitherto been lacking. PATIENTS AND METHODS Over a nine-year period, 93 patients (65 males, mean age 49 years) with narcotic-dependent pain due to chronic pancreatitis and with a dominant pancreatic duct stricture visualized by endoscopic retrograde cholangiopancreatography (ERCP), were treated by stent drainage. The duration of pain prior to treatment averaged 5.6 years. The stents were exchanged according to symptoms, and removed if the stricture was judged to be adequately dilated after stenting. RESULTS Sixty-nine patients (74%) reported complete (n = 46) or partial (n = 23) pain relief at six months. In this group of \"early responders\", 60 patients experienced sustained improvement during a mean follow-up of 4.9 years (nine had recurrent pain after a mean of 1.2 years). Stents were removed in 49 patients after a mean of 15.7 months; during a mean follow-up of 3.8 years, 36 patients remained pain-free, and 13 had a relapse of pain (11 were retreated by endoscopic drainage and subsequently became pain-free). Complications seen included mild pancreatitis (n = 4) and abscess formation secondary to stent clogging (n = 2). Most patients experienced a regression of the ductal dilation after stenting. CONCLUSION In selected patients, early responders to pancreatic stent drainage are likely to benefit over the long term. Stent removal after stricture dilation may be associated with continued pain relief.", "author" : [ { "dropping-particle" : "", "family" : "Binmoeller", "given" : "K F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jue", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seifert", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nam", "given" : "W C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Izbicki", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Soehendra", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Endoscopy", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "1995", "11", "17" ] ] }, "note" : "NULL", "page" : "638-44", "title" : "Endoscopic pancreatic stent drainage in chronic pancreatitis and a dominant stricture: long-term results.", "type" : "article-journal", "volume" : "27" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(236)", "plainTextFormattedCitation" : "(236)", "previouslyFormattedCitation" : "(236)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(236)Retrospective observational93 patients:70% men, 66% OHAge: 49 yDuration of disease: 5.6 ySevere CP: --Pain: 100%FU: 4.9 yDiabetes: 17%Steatorrhea: 9%EPSPancreatic stenting: 100% (single plastic)ESWL: 34/93 = 37%Mean duration of stenting: 15.7 mMean FU after stent removal: 3.8 yDefinitive stent removal: 49/93 = 53%Pain relief assessment severity / frequency of painPain relief at 6 m- complete46/93 = 49%- partial23/93 = 25%Complete or partial pain relief: at 4.9 y: 60/93 = 65%Surgery: 24/93 = 26%Predictive factor associated with long-term responseDuration of disease 7.0 y in non-responders vs 4.1 y in respondersNo statistical analysisLOE?: very lowPonchon (1995)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0016-5107", "PMID" : "8566637", "abstract" : "BACKGROUND Pancreatic endoscopic stenting aims to relieve abdominal pain due to chronic pancreatitis. Optimal treatment modalities and post-treatment effects have still to be determined. The object of this study was to investigate the results of a standardized protocol of endoscopic stenting. METHODS Twenty-three patients with abdominal pain due to chronic pancreatitis and stricture of the distal main pancreatic duct were treated according to the following protocol: after balloon dilation of the stenosis, a 10F stent was placed into the main pancreatic duct and then exchanged every 2 months, the total duration of drainage being 6 months. RESULTS Use of analgesics could be discontinued in 17 patients (74%) on termination of drainage, and in 12 patients (52%) 1 year later. These results were significantly associated with reduction of main pancreatic duct diameter and resolution of stricture, but were not influenced by abstinence from alcohol and pancreatic enzyme supplementation. CONCLUSIONS Pancreatic duct stenting results in short-term clinical improvement in patients with chronic pancreatitis and proximal main pancreatic duct stricture. Persistence of advantageous clinical results is to be expected in 50% of cases and when strictures have resolved.", "author" : [ { "dropping-particle" : "", "family" : "Ponchon", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bory", "given" : "R M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hedelius", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roubein", "given" : "L D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Paliard", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Napoleon", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chavaillon", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastrointestinal endoscopy", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "1995", "11" ] ] }, "note" : "NULL", "page" : "452-6", "title" : "Endoscopic stenting for pain relief in chronic pancreatitis: results of a standardized protocol.", "type" : "article-journal", "volume" : "42" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(277)", "plainTextFormattedCitation" : "(277)", "previouslyFormattedCitation" : "(277)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(277)Prospective standardized protocol23 patients:96% men, 100% OHAge: 47 yDuration of disease: --Severe CP: --Pain: 100%(Type A: 61%)FU: 14 mDiabetes: --Steatorrhea: --EPSPancreatic stenting: 100%(single plastic)ESWL: 0%Mean duration of stenting: 6 mMean FU after stent removal: 14 mDefinitive stent removal: 100%Pain relief assessment severity of pain, analgesicscomplete pain relief: 8/23 = 35%partial pain relief: 13/23 = 57%Complete or partial pain relief: 92%Stopped analgesic use: 17/23 = 74%Surgery: 3/23 = 13%Stopped analgesic use associated with in MPD by 2 mm (US)LOE?: lowSmits* (1995)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0016-5107", "PMID" : "8566639", "abstract" : "BACKGROUND Pancreatic stenting is a new nonsurgical treatment for patients with chronic pancreatitis and pain. We studied the long-term safety and efficacy of pancreatic stenting. METHODS Between 1982 and 1993, 51 patients with chronic pancreatitis and persistent pain with dominant strictures in the pancreatic duct were treated with plastic pancreatic stents. RESULTS Stent insertion was successful in 49 of 51 patients. Early complications occurred in 9 of the 51 patients (18%). Patients were followed for a median of 34 months (range 6 to 128). Nine of the 49 patients (82%) had clinical improvement. Sixteen of these 40 patients still had their stents in place. Stents were removed in 22 of the 40 patients with persistent beneficial response in all (median follow-up 28.5 months). The long-term effect of stenting could not be evaluated in the remaining 2 patients because they had a double bypass operation. Stent dysfunction occurred in 27 of the 49 patients (55%) and was successfully treated by exchanging the stent. CONCLUSIONS Pancreatic stenting was associated with minimal early complications, but stent dysfunction remained a frequent late complication. Pancreatic drainage resulted in clinical improvement in 40 of the 49 patients (82%). Twenty-two of these 40 patients maintained the beneficial response after stent removal (28.5 months).", "author" : [ { "dropping-particle" : "", "family" : "Smits", "given" : "M E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Badiga", "given" : "S M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rauws", "given" : "E A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tytgat", "given" : "G N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huibregtse", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastrointestinal endoscopy", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "1995", "11" ] ] }, "note" : "NULL", "page" : "461-7", "title" : "Long-term results of pancreatic stents in chronic pancreatitis.", "type" : "article-journal", "volume" : "42" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(237)", "plainTextFormattedCitation" : "(237)", "previouslyFormattedCitation" : "(237)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(237)Retrospective observational51 patients69% men, 61% OHAge: 45 yDuration of disease: 28.5 mSevere CP: --Pain: 100%FU: 34 mDiabetes: --Steatorrhea: --EPS (n=31)Pancreatic stenting (n=49)(single, plastic)ESWL (n=3): 6%Median duration of stenting: 6.3 mMedian FU after stent removal: 28.5 mDefinitive stent removal: 31/49 = 63%Pain relief assessment compared with the 6 m prior pancreatic stenting < 50% of pain < 50% of analgesic use < 50% of hospitalizationPain relief during stenting (n=49)Complete: 20/49 = 41%Partial: 20/49 = 41%Complete or partial: 82%Pain relief after stent removal (n=31)Complete: 12/31 = 39%Partial: 10/31 = 32%Complete or partial: 71%Surgery: 6/51 = 12%No predictive factor of clinical improvement after pancreatic stentingLOE?: lowDumonceau (1996)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0016-5107", "PMID" : "8781931", "abstract" : "BACKGROUND In severe chronic pancreatitis associated with intraductal stones, therapeutic endoscopy aims to reduce increased intraductal pressure by pancreatic sphincterotomy and stone clearance. METHODS Results of treatment were evaluated in 70 new patients who underwent pancreatic sphincterotomy and attempted stone removal. Technical results and frequency of pain relief and recurrence are compared. RESULTS Complete ductal clearance of calculi was obtained in 50% of cases. Immediate clinical improvement occurred in 95% of patients with painful attacks. No severe complications or mortality occurred. Fifty-four percent of all patients with painful chronic pancreatitis did not experience any pain recurrence within 2 years. Associations found to be statistically significant by multivariate analysis were ductal clearance and extracorporeal shock wave lithotripsy, pain disappearance and ductal clearance, pain recurrence and long evolution, and severe disease before treatment and presence of a ductal substenosis. CONCLUSIONS In this subset of patients our results indicate that the pain of chronic pancreatitis is mainly related to increased intraductal pressure. Endoscopic management appears to be a safe, conservative, alternative to surgery. The best results are obtained when it is performed early in the course of calcifying chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Dumonceau", "given" : "J M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devi\u00e8re", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moine", "given" : "O", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delhaye", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vandermeeren", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baize", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gansbeke", "given" : "D", "non-dropping-particle" : "Van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cremer", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastrointestinal endoscopy", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "1996", "6" ] ] }, "note" : "NULL", "page" : "547-55", "title" : "Endoscopic pancreatic drainage in chronic pancreatitis associated with ductal stones: long-term results.", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(251)", "plainTextFormattedCitation" : "(251)", "previouslyFormattedCitation" : "(251)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(251)Retrospective observational70 patients90% men, 80% OHAge: 47 yDuration of disease: 4.8 ySevere CP: --Pain: 90%(Type A: 31/56=55%)FU: < 2 yDiabetes: 37%Steatorrhea: 43%EPS (n=70)ESWL (n=41): 59%Pancreating stenting: 0%Technical success: 75%(complete or partial MPD clearance)Complete MPD clearance: 50%Pain relief assessmentIntensity of pain graded on a 10-point scale (VAS)Immediate pain relief(n=56 patients with pain at admission)Complete41/56 = 73%Partial12/56 = 22%Complete or partial: 95%Pain relief during 2 y FU(n = 46)Complete25/46 = 54%Partial21/46 = 46%Complete or partial: 100%Factors associated with immediate pain reliefMPD clearance (p<0.01) (complete or partial)Low frequency of pain attacks (< 2 in the 2 prior months) (p<0.05)Factors associated with sustained pain relief during 2 y FUEarlier treatment after onset of CP (p<0.005)Low frequency of pain attacks (< 2 during 2 m before ET) (p<0.05)Absence of MPD stricture (p<0.05)LOE?: lowR?sch* (2002)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1055/s-2002-34256", "ISSN" : "0013-726X", "PMID" : "12244496", "abstract" : "BACKGROUND AND STUDY AIMS Endoscopic ductal decompression therapy has become an established method of treating patients with painful obstructive chronic pancreatitis. Smaller series, mostly with a medium-term follow-up period, have reported encouraging results. The present analysis presents long-term follow-up data from a large multicenter patient cohort. PATIENTS AND METHODS Patients with painful chronic pancreatitis and with ductal obstruction due to either strictures and/or stones treated endoscopically at eight different centers underwent follow-up after 2 - 12 years (mean 4.9 years). The patients' clinical data, the rate of technical success, and complications were recorded from the charts. Follow-up data were prospectively obtained using structured questionnaires; the main parameter for evaluating treatment success was a significant reduction in pain (no pain or only weak pain). RESULTS Follow-up data were obtained from 1018 of 1211 patients treated (84%) with mainly strictures (47%), stones (18%), or strictures plus stones (32%). At the long-term follow-up, 60% of the patients had their endotherapy completed, 16% were still receiving some form of endoscopic treatment, and 24% had undergone surgery. The long-term success of endotherapy was 86% in the entire group, but only 65% in an intention-to-treat analysis. There were no significant differences between the patient groups with regard to either strictures, stones, or both. Pancreatic function was not positively affected by endoscopic therapy. CONCLUSIONS Endoscopic ductal decompression therapy offers relief of pain in two-thirds of the patients when it is used as the only form of treatment. One-quarter of the patients have to undergo surgery.", "author" : [ { "dropping-particle" : "", "family" : "R\u00f6sch", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Daniel", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scholz", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huibregtse", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smits", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schneider", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ell", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haber", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Riemann", "given" : "J-F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jakobs", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hintze", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adler", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Neuhaus", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zavoral", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zavada", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schusdziarra", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Soehendra", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "European Society of Gastrointestinal Endoscopy Research Group", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Endoscopy", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2002", "10" ] ] }, "note" : "NULL", "page" : "765-71", "title" : "Endoscopic treatment of chronic pancreatitis: a multicenter study of 1000 patients with long-term follow-up.", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(230)", "plainTextFormattedCitation" : "(230)", "previouslyFormattedCitation" : "(230)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(230)Retrospective multicenter (8 centers)1018 patients:71% men, 72% OHAge: 50 yDuration of disease: --Severe CP: --Pain: 100%(Type A: 73%)FU: 4.9 yDiabetes: 23%Steatorrhea: 37%EPS: 92%ESWL: 26%Pancreatic stenting: 57%Technical success: 88%Complete MPD clearance: 64%Completed ET: 599/758 = 79%Ongoing ET: 159/758 = 21%Pain relief assessment intensity of pain (no, weak, moderate, strong)complete pain relief: 66%partial pan relief: 19%Complete or partial pain relief: 85%Surgery: 238/1018 = 23%No difference in pain relief in patients with different ductal pathologies (i.e. strictures vs stones)Trend for higher pain relief in patients with initial technical success (p=0.06)LOE: moderateDite* (2003)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1055/s-2003-40237", "ISSN" : "0013-726X", "PMID" : "12822088", "abstract" : "BACKGROUND AND STUDY AIMS Invasive treatment for abdominal pain due to chronic pancreatitis may be either surgical or endoscopic, particularly in cases of ductal obstruction. To date, the data published on the effectiveness of these two forms of therapy have been mostly retrospective, and there have been no randomized studies. A prospective, randomized study comparing surgery with endoscopy in patients with painful obstructive chronic pancreatitis was therefore conducted. PATIENTS AND METHODS Consecutive patients with pancreatic duct obstruction and pain were invited to participate in a randomized trial comparing endotherapy and surgery, the latter consisting of resection and drainage procedures, depending on the patient's individual situation. Patients who did not agree to participation and randomization were also further assessed using the same follow-up protocol. RESULTS Of 140 eligible patients, only 72 agreed to be randomized. Surgery consisted of resection (80 %) and drainage (20 %) procedures, while endotherapy included sphincterotomy and stenting (52 %) and/or stone removal (23 %). In the entire group, the initial success rates were similar for both groups, but at the 5-year follow-up, complete absence of pain was more frequent after surgery (37 % vs. 14 %), with the rate of partial relief being similar (49 % vs. 51 %). In the randomized subgroup, results were similar (pain absence 34 % after surgery vs. 15 % after endotherapy, relief 52 % after surgery vs. 46 % after endotherapy). The increase in body weight was also greater by 20 - 25 % in the surgical group, while new-onset diabetes developed with similar frequency in both groups (34 - 43 %), again with no differences between the results for the whole group and the randomized subgroup. CONCLUSIONS Surgery is superior to endotherapy for long-term pain reduction in patients with painful obstructive chronic pancreatitis. Better selection of patients for endotherapy may be helpful in order to maximize results. Due to its low degree of invasiveness, however, endotherapy can be offered as a first-line treatment, with surgery being performed in case of failure and/or recurrence.", "author" : [ { "dropping-particle" : "", "family" : "D\u00edte", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruzicka", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zboril", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Novotn\u00fd", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Endoscopy", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2003", "7" ] ] }, "note" : "NULL", "page" : "553-558", "title" : "A Prospective, Randomized Trial Comparing Endoscopic and Surgical Therapy for Chronic Pancreatitis", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(233)", "plainTextFormattedCitation" : "(233)", "previouslyFormattedCitation" : "(233)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(233)Prospective randomized study140 patients:85% men, 88% OHAge: 41.7 y72 randomized36 ET / 36 surgery68 non randomized28 ET / 40 surgeryFU: 5 yPain: 100%Diabetes: 22%ET: n=64EPS: n=64Pancreatic stenting: 33/64 = 52%ESWL: 0%Mean duration of stenting: 16 mTechnical success: 62/64 = 97%Surgery: n=76- Resection 80%- Drainage: 20%Pain relief assessment- Melzack scoreComplete or partial pain relief after ET at 5 y FU 65% (n=64) (R + NR) 61% (n=36) (R)High risk of bias- pseudo-randomization- unconcealed allocation- lack of baseline characteristics- lack of ITT analysis- not powered- lack of optimal ET(no ESWL, no repeated ERCP)LOE: moderateVitale* (2004)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00464-003-8933-z", "ISSN" : "1432-2218", "PMID" : "15791364", "abstract" : "BACKGROUND Endoscopic retrograde cholangiopancreatography and stent placement are relatively new alternatives to surgery for the treatment of chronic pancreatitis. The objective of this study was to determine the efficacy of pancreatic duct stent placement for the treatment of chronic pancreatitis. METHODS This study included 89 patients treated with pancreatic stents between 1993 and 2002. The patients were contacted via telephone for a personal interview with regard to pain, medication usage, weight loss or gain, and eating patterns. Additionally, medication usage before and after treatment was documented from the Kentucky Cabinet for Health Services' electronic reporting system for narcotic use. RESULTS Of the 89 patients, 9 were deceased, 5 either refused to interview or could not be contacted, and 75 were interviewed. Significant weight gain exceeding 15 lb after treatment was experienced by 22%, whereas only 4% lost weight. A majority of the patients (68%) noted that they had less severe relapses or no relapses after treatment. The patients reported a decrease in pain level on a 10-point scale from 8.7 to 4.1 (53% decrease) after treatment. A decrease in pain medication usage was reported by 47% of the patients, and 83% considered their treatment successful. The Kentucky All Schedule Prescription Electronic Report (KASPER) was obtained before and after treatment for 55 patients. According to this statewide electronic reporting system, 63% had a documented decrease in narcotic use. CONCLUSION The findings of this study support the use of pancreatic duct stenting as an option before surgical intervention for these difficult-to-manage patients with chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Vitale", "given" : "G C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cothron", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vitale", "given" : "E A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rangnekar", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zavaleta", "given" : "C M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Larson", "given" : "G M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Binford", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hammond", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Surgical endoscopy", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2004", "10", "26" ] ] }, "note" : "NULL", "page" : "1431-4", "title" : "Role of pancreatic duct stenting in the treatment of chronic pancreatitis.", "type" : "article-journal", "volume" : "18" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(238)", "plainTextFormattedCitation" : "(238)", "previouslyFormattedCitation" : "(238)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(238)Retrospective analysis of a prospective database89 patients:47% menAge: 48 yPain: 100%FU (n=75): 43 mPancreatic stenting(single plastic)Mean duration of stenting: 5.3 mPain relief assessment- pain intensity score (1 – 10)Pain reduction: 62/75 = 83%Reduction in analgesic medication: 35/75 = 47%Surgery: 11/89 = 12%LOE: lowEleftheriadis* (2005)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0013-726X", "PMID" : "18556820", "abstract" : "BACKGROUND AND STUDY AIMS Although it has been proved that pancreatic stenting is effective in the symptomatic management of severe chronic pancreatitis, long-term outcomes after stent removal have not been fully evaluated. PATIENTS AND METHODS A total of 100 patients (75 men, 25 women; median age 49) with severe chronic pancreatitis and pancreatic duct strictures were successfully treated for pancreatic pain using polyethylene pancreatic stents and were followed up for at least 1 year after stent removal. The stents were exchanged \"on demand\" (in cases of recurrence of pain) and a definitive stent removal was attempted on the basis of clinical and endoscopic findings. Clinical variables were retrospectively assessed as potential predictors of re-stenting. RESULTS The etiology of the chronic pancreatitis was alcoholic (77 %), idiopathic (18 %), or hereditary (5 %). Patients were followed up for a median period of 69 months (range 14 - 163 months) after study entry, including a median period of 27 months (range 12 - 126 months) after stent removal. The median duration of pancreatic stenting before stent removal was 23 months (range 2 - 134 months). After attempted definitive stent removal, 30 patients (30 %) required re-stenting within the first year of follow-up, at a median time of 5.5 months after stent removal (range 1 - 12 months), while in 70 patients (70 %) pain control remained adequate during that period. By the end of the follow-up period a total of 38 patients had required re-stenting and four ultimately underwent pancreaticojejunostomy. Pancreas divisum was the only factor significantly associated with a higher risk of re-stenting (P = 0.002). CONCLUSIONS The majority (70 %) of patients with severe chronic pancreatitis who respond to pancreatic stenting maintain this response after definitive stent removal. However, a significantly higher re-stenting rate was observed in patients with chronic pancreatitis and pancreas divisum.", "author" : [ { "dropping-particle" : "", "family" : "Eleftherladis", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dinu", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delhaye", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moine", "given" : "O", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baize", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vandermeeren", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hookey", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devi\u00e8re", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Endoscopy", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2005", "3" ] ] }, "note" : "NULL", "page" : "223-30", "title" : "Long-term outcome after pancreatic stenting in severe chronic pancreatitis.", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(239)", "plainTextFormattedCitation" : "(239)", "previouslyFormattedCitation" : "(239)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(239)retrospective100 patients:75% men, 77% OHAge: 49 yDuration of disease: 3 ySevere CP: 86%Pain: 100%FU: 69 mFU after stent removal: 27 mDiabetes: 18%Steatorrhea: 24%EPS, ESWL (n=51)Pancreatic stenting(single plastic)Median duration of pancreatic stenting: 23 mPain relief assessment: NAComplete or partial pain relief: 62/100 = 62% at 27 m after stent removal, without pancreatic stent replacementRe-stenting within the first year of FU: 30% at a median time of 5.5 m after stent removalRe-stenting at the end of FU: 38%Surgery: 4%79% of pain relapse during the first year after stent removal97% had relapsed by 24 mPredictive factor for pancreatic re-stenting (n=30) within 1 y of stent removal: presence of PD (n=21) (12/21 vs 18/79, p=0.002)LOE: moderateCostamagna* (2006)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1055/s-2005-921069", "ISSN" : "0013-726X", "PMID" : "16528652", "abstract" : "BACKGROUND AND STUDY AIMS Dominant pancreatic duct strictures located in the head of the pancreas in patients with severe chronic pancreatitis are often managed by endoscopic placement of a single plastic stent. Patients with refractory strictures after prolonged stenting require repeated stent replacement or surgical pancreaticojejunostomy. Placement of multiple plastic stents has proved effective in managing postoperative biliary strictures. The aim of this study was to investigate the feasibility, efficacy, and long-term results of multiple stenting of refractory pancreatic strictures in severe chronic pancreatitis. PATIENTS AND METHODS 19 patients with severe chronic pancreatitis (16 men, three women; mean age 45 years) and with a single pancreatic stent through a refractory dominant stricture in the pancreatic head underwent the following protocol: (i) removal of the single pancreatic stent; (ii) balloon dilation of the stricture; (iii) insertion of the maximum number of stents allowed by the stricture tightness and the pancreatic duct diameter; and (iv) removal of stents after 6 to 12 months. RESULTS The median number of stents placed through the major or minor papilla was 3, with diameters ranging from 8.5 to 11.5 Fr and length from 4 to 7 cm. Only one patient (5.5 %) had persistent stricture after multiple stenting. During a mean follow-up of 38 months after removal, 84 % of patients were asymptomatic, and 10.5 % had symptomatic stricture recurrence. No major complications were recorded. CONCLUSION Endoscopic multiple stenting of dominant pancreatic duct strictures in chronic pancreatitis is a feasible and safe technique. Multiple pancreatic stenting is promising in obtaining persistent stricture dilation on long-term follow-up in the setting of severe chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Costamagna", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulajic", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tringali", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pandolfi", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gabbrielli", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spada", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Petruzziello", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Familiari", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mutignani", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Endoscopy", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2006", "3" ] ] }, "note" : "NULL", "page" : "254-9", "title" : "Multiple stenting of refractory pancreatic duct strictures in severe chronic pancreatitis: long-term results.", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(242)", "plainTextFormattedCitation" : "(242)", "previouslyFormattedCitation" : "(242)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(242)Prospective observational19 patients:84% men, 58% OHAge:45 yDuration of disease: --Severe CP: --Pain: --FU: 38 mDiabetes: --Steatorrhea: --Pancreatic stenting: 100%(multiple plastic)ESWL: 6/19 = 32%Mean duration of stenting: 7 mPain relief assessment: NAComplete pain relief: 16/19 = 84%LOE: lowIshihara (2006)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/00365520500383597", "ISSN" : "0036-5521", "PMID" : "16716976", "abstract" : "OBJECTIVE Stents have been used to relieve pancreatic duct stricture and upstream dilatation. However, many of these stents are straight-type stents originally manufactured for biliary use. A plastic stent that was developed for use in the pancreatic duct was used in this study and its usefulness investigated. MATERIAL AND METHODS The stent (s-type stent: 10 Fr in diameter) has two alternate flexions and the shape resembles the tilde mark \" approximately \" in appearance. After obtaining informed consent, stents were placed in 20 patients with abdominal pain caused by chronic pancreatitis and stricture of the distal main pancreatic duct. The stents were removed according to the clinical manifestations and replaced with new ones if the stricture persisted. RESULTS In total, 33 stents were placed in 20 patients. Pain relief was attained in 19 patients (95%). The stricture improved after one stenting in 8 patients (40%). Owing to persistent stricture, the stenting was repeated in 11 patients. The 50% stent indwelling period was 369.0 days. No proximal or distal migration of the stent occurred and there were no serious complications. CONCLUSIONS In view of its long durability as a stent and no migration, the s-stent is safe and useful for the management of pancreatic ductal strictures in patients with chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Ishihara", "given" : "Takeshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamaguchi", "given" : "Taketo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seza", "given" : "Katsushi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tadenuma", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saisho", "given" : "Hiromitsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of gastroenterology", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2006", "6", "8" ] ] }, "note" : "NULL", "page" : "744-50", "title" : "Efficacy of s-type stents for the treatment of the main pancreatic duct stricture in patients with chronic pancreatitis.", "type" : "article-journal", "volume" : "41" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(278)", "plainTextFormattedCitation" : "(278)", "previouslyFormattedCitation" : "(278)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(278)NA20 patients:90% men, 95% OHAge: 52.4 yDuration of disease: --Severe CP: --Pain: --FU after stent removal: 10.5 mDiabetes: --Steatorrhea: --Pancreatic stenting: n=20EPSESWL: 9/20 = 45%Mean duration of stent patency: 12 mPain relief assessment4-grade scale: none, mild, moderate, severePain relief (none, mild) after stent removal: 18/20 = 90%LOE: lowFarnbacher* (2006)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/00365520510024098", "ISSN" : "0036-5521", "PMID" : "16373284", "abstract" : "OBJECTIVE In the past 15 years there have been tremendous advances in endoscopic management of chronic pancreatitis (CP). However, the value of endoscopic pancreatic stenting is still debatable. MATERIAL AND METHODS In 98 patients suffering from symptomatic CP (84 M, 14 F, 49+/-12, age range 23-83 years) endotherapy including temporary stenting of the pancreatic duct was performed. After final stent removal, indicating the primary end-point of endotherapy, 96 patients were followed for 35+/-28 (8 days-111) months. All data were assessed retrospectively. RESULTS As well as other endoscopic procedures, a total of 358 prostheses were inserted in the pancreatic duct and left in place for 3+/-1 (1 day-11) months. Total stent treatment time was 10+/-10 (6 days-49) months. At 46+/-27 (4-111) months after limited endotherapy, 57 patients had no need for secondary intervention, two-thirds were even without further pain sensations. In 22 patients, surgical treatment and in 17 patients further endoscopic therapy became necessary, which was significantly correlated with continued alcohol consumption. CONCLUSIONS Temporary stent placement as a part of interventional endoscopic therapy in CP shows a high rate of technical and long-term clinical success, with no need for secondary treatment in a remarkable number of patients. Continued cessation of alcohol consumption supports the treatment benefit significantly.", "author" : [ { "dropping-particle" : "", "family" : "Farnbacher", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "M\u00fchldorfer", "given" : "Steffen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wehler", "given" : "Markus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fischer", "given" : "Bernhard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hahn", "given" : "Eckhart G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schneider", "given" : "H Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of gastroenterology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2006", "1", "8" ] ] }, "note" : "NULL", "page" : "111-7", "title" : "Interventional endoscopic therapy in chronic pancreatitis including temporary stenting: a definitive treatment?", "type" : "article-journal", "volume" : "41" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(240)", "plainTextFormattedCitation" : "(240)", "previouslyFormattedCitation" : "(240)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(240)Retrospective98 patients:86% men, 73% OHAge: 49 yDuration of disease: --Severe CP: 88%Pain: 89%(Type A: 68%)FU after stent removal: 3.8 y (n=57) Diabetes: --Steatorrhea: --EPS (n=76)Pancreatic stenting (single plastic): n=98ESWL (n=60)Mean duration of pancreatic stenting: 10 mPain relief assessmentVAS (intensity)Complete pain relief: 53/96Partial pain relief: 22/96Complete or partial: 75/96 = 78%Re-stenting: 17/96 = 18%Surgery: 22/96 = 23%LOE: lowWeber* (2007)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/mpa.0b013e3180325ba6", "ISSN" : "1536-4828", "PMID" : "17414050", "abstract" : "OBJECTIVES Obstruction of the pancreatic duct is a common feature of chronic pancreatitis and often requires interventional therapy. The current prospective study investigated clinical success in 19 patients after initial endoscopic retrograde pancreaticography and relapse rates during a 2-year follow-up period. METHODS Seventeen of 19 patients with chronic pancreatitis (stage III according to the Cambridge classification) were treated by sphincterotomy and stent insertion. Endoscopic retrograde pancreaticography failed in 2 patients. RESULTS Strictures were cannulated, dilated, and stones were removed with a dormia basket in 13 of 17 patients. Extracorporeal shock wave lithotripsy was necessary in 5 patients. Polyethylene stents (7F-11.5F) were placed into the dilated pancreatic duct. Mean duration of internal pancreatic stenting was 5.6 months. Three of 17 patients had recurrence of pain during the first follow-up year after stent extraction; in the second follow-up year, another 2 patients had a relapse. Overall, patients' assessment of the stent therapy revealed complete satisfaction in 17 of 19 patients. CONCLUSIONS Endoscopic stent therapy is a safe, minimally invasive, and effective procedure in patients experiencing pain attacks during chronic pancreatitis associated with dilated pancreatic duct. According to our results, a relapse rate of approximately 30% can be expected within 2 years after stent extraction. These patients may be treated by repeated stent therapy.", "author" : [ { "dropping-particle" : "", "family" : "Weber", "given" : "Andreas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schneider", "given" : "Jochen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Neu", "given" : "Bruno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meining", "given" : "Alexander", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Born", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schmid", "given" : "Roland M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prinz", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreas", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2007", "4" ] ] }, "note" : "NULL", "page" : "287-94", "title" : "Endoscopic stent therapy for patients with chronic pancreatitis: results from a prospective follow-up study.", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(241)", "plainTextFormattedCitation" : "(241)", "previouslyFormattedCitation" : "(241)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(241)Prospective observational19 patients:63% men, 74% OHAge: 54 yDuration of disease: 3 ySevere CP: 100%Pain: 100%(Type A: 58%)FU: 2 yDiabetes: 26%Steatorrhea: 5%EPS: n=19Pancreatic stenting: n=17(single plastic)ESWL: n=5 (26%)Technical success: 17/19 = 89%)Mean duration of stenting: 5.6 mPain relief assessment- VAS (intensity 0 – 10)- in pain medicationComplete or partial pain relief at 1 y: 14/19 = 74% at 2 y: 11/19 = 58%LOE: lowRutter* (2010)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00268-010-0713-z", "ISSN" : "1432-2323", "PMID" : "20645098", "abstract" : "OBJECTIVE Patients with chronic pancreatitis usually have a long and debilitating history of disease with frequent hospital admissions, episodes of intractable pain and multiple interventions. The sequences of treatment at initial presentation, endoscopy, surgery, or conservative treatment may affect the time course and admissions needed for disease control, thereby determining quality of life and overall outcome. METHODS A total of 292 patients with initial endoscopic, surgical, or conservative pharmacological treatment were retrospectively analyzed regarding frequency of interventions, days in hospital, symptom-free intervals, morbidity, and mortality. Quality of life (QoL) at the latest follow-up was measured by two standardized quality of life questionnaires (EORTC C30 and PAN26). RESULTS Endoscopic treatment was initially performed in 150 (51.4%) patients, whereas 99 (33.9%) underwent surgery and 43 (14.7%) patients were treated conservatively at their initial presentation. Patients who underwent surgery had a significantly shorter time in the hospital (25.3\u00a0\u00b1\u00a024.6, 34.4\u00a0\u00b1\u00a035.1, 61.1\u00a0\u00b1\u00a037.9; P\u00a0<\u00a00.001), fewer subsequent therapies (0.43\u00a0\u00b1\u00a01.0, 2.1\u00a0\u00b1\u00a02.4, 3.1\u00a0\u00b1\u00a03.0; P\u00a0\u2264\u00a00.001), and a longer relapse-free interval (P\u00a0=\u00a00.004) compared with endoscopically treated patients. The overall complication rate was 32% both after surgery and endoscopy. Infectious-related complications occurred more often after surgical treatment (P\u00a0\u2264\u00a00.001), whereas patients after endoscopic intervention developed acute or chronic pancreatitis or pseudocyst formation (P\u00a0=\u00a00.023). CONCLUSIONS Patients who undergo surgery as their initial treatment for chronic pancreatitis require less consecutive interventions, a shorter hospital stay, and have a better quality of life compared with any other treatment. Surgery should therefore be considered early for the treatment of chronic pancreatitis, when endoscopic or conservative treatment fails and patients require further intervention.", "author" : [ { "dropping-particle" : "", "family" : "Rutter", "given" : "Karoline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferlitsch", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sautner", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "P\u00fcsp\u00f6k", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "G\u00f6tzinger", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gangl", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schindl", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "World journal of surgery", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2010", "11", "20" ] ] }, "page" : "2642-7", "title" : "Hospitalization, frequency of interventions, and quality of life after endoscopic, surgical, or conservative treatment in patients with chronic pancreatitis.", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(279)", "plainTextFormattedCitation" : "(279)", "previouslyFormattedCitation" : "(279)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(279)Retrospective comparative292 patients 150 ET:70% men, 53% OHAge: 51.3 yDuration of disease: --Severe CP: --Pain: 28% (81/292)FU: 2.8 yDiabetes: --Steatorrhea: --Endoscopy: n=150Pancreatic and/or bile duct stenting: n=60EPS: n=66Surgery: n=99Conservative: n=43Technical success: --Relapse-free interval: 4.8 7.0 m (for endoscopy group)LOE: very lowClarke* (2012)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.cgh.2011.12.040", "ISSN" : "1542-7714", "PMID" : "22245964", "abstract" : "BACKGROUND & AIMS Endoscopic therapy (ET) frequently is used to treat patients with painful chronic pancreatitis (CP), but little is known about outcomes of patients for whom ET was not successful who then underwent surgery, or outcomes after ET compared with only medical treatment. We evaluated use and long-term effectiveness of ET in a well-defined cohort of patients with CP. METHODS We analyzed data from 146 patients with CP who participated in the North American Pancreatitis Study 2 at the University of Pittsburgh Medical Center from 2000 to 2006; 71 (49%) patients received ET at the University of Pittsburgh Medical Center. Success of ET and surgery were defined by cessation of narcotic therapy and resolution of episodes of acute pancreatitis. Disease progression was followed up from its onset until January 1, 2011 (mean, 8.2 \u00b1 4.7 y). RESULTS Patients who underwent ET had more symptoms (pain, recurrent pancreatitis) and had more complex pancreatic morphology (based on imaging) than patients who received medical therapy. ET had a high rate of technical success (60 of 71 cases; 85%); its rates of clinical success were 51% for 28 of 55 patients for whom follow-up data were available (mean time, 4.8 \u00b1 3.0 y) and 50% for 12 of 24 patients who underwent surgery after receiving ET. Patients who responded to ET were significantly older, had a shorter duration of disease before ET, had less constant pain, and required fewer daily narcotics than patients who did not respond to ET. Among the 36 symptomatic patients who received medical therapy and were followed up for a mean period of 5.7 \u00b1 4.1 years, 31% improved and 53% had no change in symptoms; of these, 21% underwent surgery. CONCLUSIONS ET is clinically successful for 50% of patients with symptomatic CP. When ET is not successful, surgery has successful outcomes in 50% of patients. Symptoms resolve in 31% of symptomatic patients who receive only medical therapy.", "author" : [ { "dropping-particle" : "", "family" : "Clarke", "given" : "Bridger", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slivka", "given" : "Adam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tomizawa", "given" : "Yutaka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanders", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Papachristou", "given" : "Georgios I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Whitcomb", "given" : "David C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yadav", "given" : "Dhiraj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2012", "7" ] ] }, "note" : "NULL", "page" : "795-802", "title" : "Endoscopic therapy is effective for patients with chronic pancreatitis.", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(253)", "plainTextFormattedCitation" : "(253)", "previouslyFormattedCitation" : "(253)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(253)Retrospective analysis of a prospective database85 patients:51% men, 41% OHAge: 41 yDuration of disease: --Severe CP: --Pain: 72%(Type A: 58%)FU (n=63): 4.8 yDiabetes: 8%Steatorrhea: 21%ET in 71 patientsEPS: n=43 (61%)ESWL: n=6 (8%)Pancreatic stenting: n=53 (75%)Technical success complete or partial: 60/70 = 86%Pain relief assessment- frequency of pain- discontinuation of narcotic medicationsClinical success (n=55)Complete: 23/55 = 42%Partial: 5/55 = 9%Complete or partial clinical success: 51%Factors associated with long-term clinical response to ET (n=28 vs n=27)Less constant pain: 21% vs 52%, p=0.031Less daily narcotics: 14% vs 56%, p=0.001Shorter duration between onset of CP and start of ET: 4 m vs 40 m, p=0.017No association with specific baseline morphologic characteristicsLOE: lowWeber* (2013)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3748/wjg.v19.i5.715", "ISSN" : "2219-2840", "PMID" : "23430281", "abstract" : "AIM This study analyzed clinical long-term outcomes after endoscopic therapy, including the incidence and treatment of relapse. METHODS This study included 19 consecutive patients (12 male, 7 female, median age 54 years) with obstructive chronic pancreatitis who were admitted to the 2(nd) Medical Department of the Technical University of Munich. All patients presented severe chronic pancreatitis (stage III\u00b0) according to the Cambridge classification. The majority of the patients suffered intermittent pain attacks. 6 of 19 patients had strictures of the pancreatic duct; 13 of 19 patients had strictures and stones. The first endoscopic retrograde pancreatography (ERP) included an endoscopic sphincterotomy, dilatation of the pancreatic duct, and stent placement. The first control ERP was performed 4 wk after the initial intervention, and the subsequent control ERP was performed after 3 mo to re-evaluate the clinical and morphological conditions. Clinical follow-up was performed annually to document the course of pain and the management of relapse. The course of pain was assessed by a pain scale from 0 to 10. The date and choice of the therapeutic procedure were documented in case of relapse. RESULTS Initial endoscopic intervention was successfully completed in 17 of 19 patients. All 17 patients reported partial or complete pain relief after endoscopic intervention. Endoscopic therapy failed in 2 patients. Both patients were excluded from further analysis. One failed patient underwent surgery, and the other patient was treated conservatively with pain medication. Seventeen of 19 patients were followed after the successful completion of endoscopic stent therapy. Three of 17 patients were lost to follow-up. One patient was not available for interviews after the 1(st) year of follow-up. Two patients died during the 3(rd) year of follow-up. In both patients chronic pancreatitis was excluded as the cause of death. One patient died of myocardial infarction, and one patient succumbed to pneumonia. All three patients were excluded from follow-up analysis. Follow-up was successfully completed in 14 of 17 patients. 4 patients at time point 3, 2 patients at time point 4, 3 patients at time point 5 and 2 patients at time point 6 and time point 7 used continuous pain medication after endoscopic therapy. No relapse occurred in 57% (8/14) of patients. All 8 patients exhibited significantly reduced or no pain complaints during the 5-year follow-up. Seven of 8 patients were\u2026", "author" : [ { "dropping-particle" : "", "family" : "Weber", "given" : "Andreas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schneider", "given" : "Jochen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Neu", "given" : "Bruno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meining", "given" : "Alexander", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Born", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delius", "given" : "Stefan", "non-dropping-particle" : "von", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bajbouj", "given" : "Monther", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schmid", "given" : "Roland M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alg\u00fcl", "given" : "Hana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prinz", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "World journal of gastroenterology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2013", "2", "7" ] ] }, "note" : "NULL", "page" : "715-20", "title" : "Endoscopic stent therapy in patients with chronic pancreatitis: a 5-year follow-up study.", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(280)", "plainTextFormattedCitation" : "(280)", "previouslyFormattedCitation" : "(280)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(280)Prospective observational case series19 patients:63% men, 74% OHAge: 54 yDuration of disease: 3 ySevere CP: 100%Pain: 100%(Type A: 58%)FU: up to 5 yDiabetes: 26%Steatorrhea: 5%Pancreatic stenting: n=17(single plastic)ESWL: n=5 (26%)Technical success: 17/19 = 89%Mean duration of stenting: 5.6 mPain relief assessment- VAS (intensity 0 – 10)- in pain medicationComplete or partial pain relief at 5 y: 8/19 = 42%Surgery: 3/19 = 16%LOE: very lowHe* (2014)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/MPA.0000000000000140", "ISSN" : "1536-4828", "PMID" : "24717828", "abstract" : "OBJECTIVE The aim of this study was to evaluate the M-ANNHEIM classification system to categorize patients with chronic pancreatitis (CP). METHODS All symptomatic patients recruited from the gastroenterology outpatient clinic of Changhai Hospital (n = 89) were routinely evaluated by magnetic resonance cholangiopancreatography and contrast-enhanced computed tomography. M-ANNHEIM clinical staging was used to categorize patients. The primary outcome measure was pain during the 2-year follow-up period, expressed as mean Izbicki pain scores obtained before and after endotherapy. RESULTS There was a significant improvement in mean (SD) Izbicki pain scores obtained at 24 months among patients receiving endoscopic therapy at stage 1a compared with those at stage 1b (4.9 [3.0] vs 14.5 [6.9], P = 0.012). Furthermore, significantly more patients receiving endoscopic therapy at stage 1a achieved complete + partial pain relief after 2-year follow-up than those at stage 1b (95.2% vs 78.0%, P = 0.021). There was no exocrine or endocrine insufficiency, but a significantly greater number of patients treated at stage 1a had post-endoscopic retrograde cholangiopancreatography pancreatitis compared with those at stage 1b (10.5% vs 2.7%, P = 0.025). CONCLUSIONS We demonstrated that a sophisticated M-ANNHEIM classification system for CP will improve diagnosis by allowing for more timely intervention. Furthermore, prompt treatment of CP may achieve improved pain relief and patient outcomes.", "author" : [ { "dropping-particle" : "", "family" : "He", "given" : "Yuan-Xiang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Hong-Wei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sun", "given" : "Xiao-Tian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ye", "given" : "Zhou", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Wei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lai", "given" : "Xiao-Wei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Xin-Tao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Liang-Hao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sun", "given" : "Chang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liao", "given" : "Zhuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Zhao-Shen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreas", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2014", "8" ] ] }, "note" : "NULL", "page" : "829-33", "title" : "Endoscopic management of early-stage chronic pancreatitis based on M-ANNHEIM classification system: a prospective study.", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(254)", "plainTextFormattedCitation" : "(254)", "previouslyFormattedCitation" : "(254)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(254)prospective360 patients:89 stage I M-ANNHEIM classification72% men, 38% OHAge: --Duration of disease: --Severe CP: 36/89 = 40%Mild CP: 32/89 = 36%Pain: --FU (n=83): 24 mDiabetes: 0%Steatorrhea: 0%ESWL: 0%EPSStone extraction: 36/89 = 40%Pancreatic stenting: 76/89 = 87% (single plastic)Technical success: NAMean duration of pancreatic stenting: 11 mPain relief assessmentIzbicki pain score before ET, at 24 mComplete pain relief: 54/83 = 65%Partial pain relief: 18/83 = 22%Complete or partial pain relief: 87%Surgery: 4/89 = 4%Mild CP in 36% of patients (i.e. no abnormality of the MPD) but 87% of pancreatic stenting to treat MPD stricture!Better clinical results if early treatment (before pancreatic endocrine/exocrine insufficiency)?LOE: lowTable 4S= Endoscopy ESWL ( 50%) Studies 50 patients and FU 24 mAuthor (year) (ref)DesignNumber of patientsComplete or partial pain reliefFU (months)Comments (LOE)Binmoeller (1995)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1055/s-2007-1005780", "ISSN" : "0013-726X", "PMID" : "8903975", "abstract" : "BACKGROUND AND STUDY AIMS Endoscopic pancreatic stent drainage has been reported to relieve pain due to chronic pancreatitis in patients with ductal outflow obstruction. However, data regarding the long-term results, as presented here, have hitherto been lacking. PATIENTS AND METHODS Over a nine-year period, 93 patients (65 males, mean age 49 years) with narcotic-dependent pain due to chronic pancreatitis and with a dominant pancreatic duct stricture visualized by endoscopic retrograde cholangiopancreatography (ERCP), were treated by stent drainage. The duration of pain prior to treatment averaged 5.6 years. The stents were exchanged according to symptoms, and removed if the stricture was judged to be adequately dilated after stenting. RESULTS Sixty-nine patients (74%) reported complete (n = 46) or partial (n = 23) pain relief at six months. In this group of \"early responders\", 60 patients experienced sustained improvement during a mean follow-up of 4.9 years (nine had recurrent pain after a mean of 1.2 years). Stents were removed in 49 patients after a mean of 15.7 months; during a mean follow-up of 3.8 years, 36 patients remained pain-free, and 13 had a relapse of pain (11 were retreated by endoscopic drainage and subsequently became pain-free). Complications seen included mild pancreatitis (n = 4) and abscess formation secondary to stent clogging (n = 2). Most patients experienced a regression of the ductal dilation after stenting. CONCLUSION In selected patients, early responders to pancreatic stent drainage are likely to benefit over the long term. Stent removal after stricture dilation may be associated with continued pain relief.", "author" : [ { "dropping-particle" : "", "family" : "Binmoeller", "given" : "K F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jue", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seifert", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nam", "given" : "W C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Izbicki", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Soehendra", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Endoscopy", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "1995", "11", "17" ] ] }, "note" : "NULL", "page" : "638-44", "title" : "Endoscopic pancreatic stent drainage in chronic pancreatitis and a dominant stricture: long-term results.", "type" : "article-journal", "volume" : "27" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(236)", "plainTextFormattedCitation" : "(236)", "previouslyFormattedCitation" : "(236)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(236) Retrospective9365% (60 / 93)59Predictive factor of long-term responseShorter duration of diseaseLOE: very lowSmits (1995)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0016-5107", "PMID" : "8566639", "abstract" : "BACKGROUND Pancreatic stenting is a new nonsurgical treatment for patients with chronic pancreatitis and pain. We studied the long-term safety and efficacy of pancreatic stenting. METHODS Between 1982 and 1993, 51 patients with chronic pancreatitis and persistent pain with dominant strictures in the pancreatic duct were treated with plastic pancreatic stents. RESULTS Stent insertion was successful in 49 of 51 patients. Early complications occurred in 9 of the 51 patients (18%). Patients were followed for a median of 34 months (range 6 to 128). Nine of the 49 patients (82%) had clinical improvement. Sixteen of these 40 patients still had their stents in place. Stents were removed in 22 of the 40 patients with persistent beneficial response in all (median follow-up 28.5 months). The long-term effect of stenting could not be evaluated in the remaining 2 patients because they had a double bypass operation. Stent dysfunction occurred in 27 of the 49 patients (55%) and was successfully treated by exchanging the stent. CONCLUSIONS Pancreatic stenting was associated with minimal early complications, but stent dysfunction remained a frequent late complication. Pancreatic drainage resulted in clinical improvement in 40 of the 49 patients (82%). Twenty-two of these 40 patients maintained the beneficial response after stent removal (28.5 months).", "author" : [ { "dropping-particle" : "", "family" : "Smits", "given" : "M E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Badiga", "given" : "S M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rauws", "given" : "E A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tytgat", "given" : "G N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huibregtse", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastrointestinal endoscopy", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "1995", "11" ] ] }, "note" : "NULL", "page" : "461-7", "title" : "Long-term results of pancreatic stents in chronic pancreatitis.", "type" : "article-journal", "volume" : "42" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(237)", "plainTextFormattedCitation" : "(237)", "previouslyFormattedCitation" : "(237)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(237) Retrospective5143% (22 / 51)34LOE: lowR?sch (2002)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1055/s-2002-34256", "ISSN" : "0013-726X", "PMID" : "12244496", "abstract" : "BACKGROUND AND STUDY AIMS Endoscopic ductal decompression therapy has become an established method of treating patients with painful obstructive chronic pancreatitis. Smaller series, mostly with a medium-term follow-up period, have reported encouraging results. The present analysis presents long-term follow-up data from a large multicenter patient cohort. PATIENTS AND METHODS Patients with painful chronic pancreatitis and with ductal obstruction due to either strictures and/or stones treated endoscopically at eight different centers underwent follow-up after 2 - 12 years (mean 4.9 years). The patients' clinical data, the rate of technical success, and complications were recorded from the charts. Follow-up data were prospectively obtained using structured questionnaires; the main parameter for evaluating treatment success was a significant reduction in pain (no pain or only weak pain). RESULTS Follow-up data were obtained from 1018 of 1211 patients treated (84%) with mainly strictures (47%), stones (18%), or strictures plus stones (32%). At the long-term follow-up, 60% of the patients had their endotherapy completed, 16% were still receiving some form of endoscopic treatment, and 24% had undergone surgery. The long-term success of endotherapy was 86% in the entire group, but only 65% in an intention-to-treat analysis. There were no significant differences between the patient groups with regard to either strictures, stones, or both. Pancreatic function was not positively affected by endoscopic therapy. CONCLUSIONS Endoscopic ductal decompression therapy offers relief of pain in two-thirds of the patients when it is used as the only form of treatment. One-quarter of the patients have to undergo surgery.", "author" : [ { "dropping-particle" : "", "family" : "R\u00f6sch", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Daniel", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scholz", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huibregtse", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smits", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schneider", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ell", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haber", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Riemann", "given" : "J-F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jakobs", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hintze", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adler", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Neuhaus", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zavoral", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zavada", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schusdziarra", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Soehendra", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "European Society of Gastrointestinal Endoscopy Research Group", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Endoscopy", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2002", "10" ] ] }, "note" : "NULL", "page" : "765-71", "title" : "Endoscopic treatment of chronic pancreatitis: a multicenter study of 1000 patients with long-term follow-up.", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(230)", "plainTextFormattedCitation" : "(230)", "previouslyFormattedCitation" : "(230)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(230) Retrospective101885% (865 / 1018)59LOE: moderateDite (2003)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1055/s-2003-40237", "ISSN" : "0013-726X", "PMID" : "12822088", "abstract" : "BACKGROUND AND STUDY AIMS Invasive treatment for abdominal pain due to chronic pancreatitis may be either surgical or endoscopic, particularly in cases of ductal obstruction. To date, the data published on the effectiveness of these two forms of therapy have been mostly retrospective, and there have been no randomized studies. A prospective, randomized study comparing surgery with endoscopy in patients with painful obstructive chronic pancreatitis was therefore conducted. PATIENTS AND METHODS Consecutive patients with pancreatic duct obstruction and pain were invited to participate in a randomized trial comparing endotherapy and surgery, the latter consisting of resection and drainage procedures, depending on the patient's individual situation. Patients who did not agree to participation and randomization were also further assessed using the same follow-up protocol. RESULTS Of 140 eligible patients, only 72 agreed to be randomized. Surgery consisted of resection (80 %) and drainage (20 %) procedures, while endotherapy included sphincterotomy and stenting (52 %) and/or stone removal (23 %). In the entire group, the initial success rates were similar for both groups, but at the 5-year follow-up, complete absence of pain was more frequent after surgery (37 % vs. 14 %), with the rate of partial relief being similar (49 % vs. 51 %). In the randomized subgroup, results were similar (pain absence 34 % after surgery vs. 15 % after endotherapy, relief 52 % after surgery vs. 46 % after endotherapy). The increase in body weight was also greater by 20 - 25 % in the surgical group, while new-onset diabetes developed with similar frequency in both groups (34 - 43 %), again with no differences between the results for the whole group and the randomized subgroup. CONCLUSIONS Surgery is superior to endotherapy for long-term pain reduction in patients with painful obstructive chronic pancreatitis. Better selection of patients for endotherapy may be helpful in order to maximize results. Due to its low degree of invasiveness, however, endotherapy can be offered as a first-line treatment, with surgery being performed in case of failure and/or recurrence.", "author" : [ { "dropping-particle" : "", "family" : "D\u00edte", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruzicka", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zboril", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Novotn\u00fd", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Endoscopy", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2003", "7" ] ] }, "note" : "NULL", "page" : "553-558", "title" : "A Prospective, Randomized Trial Comparing Endoscopic and Surgical Therapy for Chronic Pancreatitis", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(233)", "plainTextFormattedCitation" : "(233)", "previouslyFormattedCitation" : "(233)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(233) Prospective partially randomized6466% (42 / 64)60LOE: moderateVitale (2004)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00464-003-8933-z", "ISSN" : "1432-2218", "PMID" : "15791364", "abstract" : "BACKGROUND Endoscopic retrograde cholangiopancreatography and stent placement are relatively new alternatives to surgery for the treatment of chronic pancreatitis. The objective of this study was to determine the efficacy of pancreatic duct stent placement for the treatment of chronic pancreatitis. METHODS This study included 89 patients treated with pancreatic stents between 1993 and 2002. The patients were contacted via telephone for a personal interview with regard to pain, medication usage, weight loss or gain, and eating patterns. Additionally, medication usage before and after treatment was documented from the Kentucky Cabinet for Health Services' electronic reporting system for narcotic use. RESULTS Of the 89 patients, 9 were deceased, 5 either refused to interview or could not be contacted, and 75 were interviewed. Significant weight gain exceeding 15 lb after treatment was experienced by 22%, whereas only 4% lost weight. A majority of the patients (68%) noted that they had less severe relapses or no relapses after treatment. The patients reported a decrease in pain level on a 10-point scale from 8.7 to 4.1 (53% decrease) after treatment. A decrease in pain medication usage was reported by 47% of the patients, and 83% considered their treatment successful. The Kentucky All Schedule Prescription Electronic Report (KASPER) was obtained before and after treatment for 55 patients. According to this statewide electronic reporting system, 63% had a documented decrease in narcotic use. CONCLUSION The findings of this study support the use of pancreatic duct stenting as an option before surgical intervention for these difficult-to-manage patients with chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Vitale", "given" : "G C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cothron", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vitale", "given" : "E A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rangnekar", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zavaleta", "given" : "C M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Larson", "given" : "G M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Binford", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hammond", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Surgical endoscopy", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2004", "10", "26" ] ] }, "note" : "NULL", "page" : "1431-4", "title" : "Role of pancreatic duct stenting in the treatment of chronic pancreatitis.", "type" : "article-journal", "volume" : "18" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(238)", "plainTextFormattedCitation" : "(238)", "previouslyFormattedCitation" : "(238)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(238) Retrospective8970% (62 / 89)43LOE: lowEleftheriadis (2005)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0013-726X", "PMID" : "18556820", "abstract" : "BACKGROUND AND STUDY AIMS Although it has been proved that pancreatic stenting is effective in the symptomatic management of severe chronic pancreatitis, long-term outcomes after stent removal have not been fully evaluated. PATIENTS AND METHODS A total of 100 patients (75 men, 25 women; median age 49) with severe chronic pancreatitis and pancreatic duct strictures were successfully treated for pancreatic pain using polyethylene pancreatic stents and were followed up for at least 1 year after stent removal. The stents were exchanged \"on demand\" (in cases of recurrence of pain) and a definitive stent removal was attempted on the basis of clinical and endoscopic findings. Clinical variables were retrospectively assessed as potential predictors of re-stenting. RESULTS The etiology of the chronic pancreatitis was alcoholic (77 %), idiopathic (18 %), or hereditary (5 %). Patients were followed up for a median period of 69 months (range 14 - 163 months) after study entry, including a median period of 27 months (range 12 - 126 months) after stent removal. The median duration of pancreatic stenting before stent removal was 23 months (range 2 - 134 months). After attempted definitive stent removal, 30 patients (30 %) required re-stenting within the first year of follow-up, at a median time of 5.5 months after stent removal (range 1 - 12 months), while in 70 patients (70 %) pain control remained adequate during that period. By the end of the follow-up period a total of 38 patients had required re-stenting and four ultimately underwent pancreaticojejunostomy. Pancreas divisum was the only factor significantly associated with a higher risk of re-stenting (P = 0.002). CONCLUSIONS The majority (70 %) of patients with severe chronic pancreatitis who respond to pancreatic stenting maintain this response after definitive stent removal. However, a significantly higher re-stenting rate was observed in patients with chronic pancreatitis and pancreas divisum.", "author" : [ { "dropping-particle" : "", "family" : "Eleftherladis", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dinu", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delhaye", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moine", "given" : "O", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baize", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vandermeeren", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hookey", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devi\u00e8re", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Endoscopy", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2005", "3" ] ] }, "note" : "NULL", "page" : "223-30", "title" : "Long-term outcome after pancreatic stenting in severe chronic pancreatitis.", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(239)", "plainTextFormattedCitation" : "(239)", "previouslyFormattedCitation" : "(239)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(239) Retrospective10062% (62 /100)69LOE: moderateFarnbacher (2006)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/00365520510024098", "ISSN" : "0036-5521", "PMID" : "16373284", "abstract" : "OBJECTIVE In the past 15 years there have been tremendous advances in endoscopic management of chronic pancreatitis (CP). However, the value of endoscopic pancreatic stenting is still debatable. MATERIAL AND METHODS In 98 patients suffering from symptomatic CP (84 M, 14 F, 49+/-12, age range 23-83 years) endotherapy including temporary stenting of the pancreatic duct was performed. After final stent removal, indicating the primary end-point of endotherapy, 96 patients were followed for 35+/-28 (8 days-111) months. All data were assessed retrospectively. RESULTS As well as other endoscopic procedures, a total of 358 prostheses were inserted in the pancreatic duct and left in place for 3+/-1 (1 day-11) months. Total stent treatment time was 10+/-10 (6 days-49) months. At 46+/-27 (4-111) months after limited endotherapy, 57 patients had no need for secondary intervention, two-thirds were even without further pain sensations. In 22 patients, surgical treatment and in 17 patients further endoscopic therapy became necessary, which was significantly correlated with continued alcohol consumption. CONCLUSIONS Temporary stent placement as a part of interventional endoscopic therapy in CP shows a high rate of technical and long-term clinical success, with no need for secondary treatment in a remarkable number of patients. Continued cessation of alcohol consumption supports the treatment benefit significantly.", "author" : [ { "dropping-particle" : "", "family" : "Farnbacher", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "M\u00fchldorfer", "given" : "Steffen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wehler", "given" : "Markus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fischer", "given" : "Bernhard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hahn", "given" : "Eckhart G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schneider", "given" : "H Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Scandinavian journal of gastroenterology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2006", "1", "8" ] ] }, "note" : "NULL", "page" : "111-7", "title" : "Interventional endoscopic therapy in chronic pancreatitis including temporary stenting: a definitive treatment?", "type" : "article-journal", "volume" : "41" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(240)", "plainTextFormattedCitation" : "(240)", "previouslyFormattedCitation" : "(240)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(240) Retrospective9877% (75 / 98)46LOE: lowRutter (2010)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00268-010-0713-z", "ISSN" : "1432-2323", "PMID" : "20645098", "abstract" : "OBJECTIVE Patients with chronic pancreatitis usually have a long and debilitating history of disease with frequent hospital admissions, episodes of intractable pain and multiple interventions. The sequences of treatment at initial presentation, endoscopy, surgery, or conservative treatment may affect the time course and admissions needed for disease control, thereby determining quality of life and overall outcome. METHODS A total of 292 patients with initial endoscopic, surgical, or conservative pharmacological treatment were retrospectively analyzed regarding frequency of interventions, days in hospital, symptom-free intervals, morbidity, and mortality. Quality of life (QoL) at the latest follow-up was measured by two standardized quality of life questionnaires (EORTC C30 and PAN26). RESULTS Endoscopic treatment was initially performed in 150 (51.4%) patients, whereas 99 (33.9%) underwent surgery and 43 (14.7%) patients were treated conservatively at their initial presentation. Patients who underwent surgery had a significantly shorter time in the hospital (25.3\u00a0\u00b1\u00a024.6, 34.4\u00a0\u00b1\u00a035.1, 61.1\u00a0\u00b1\u00a037.9; P\u00a0<\u00a00.001), fewer subsequent therapies (0.43\u00a0\u00b1\u00a01.0, 2.1\u00a0\u00b1\u00a02.4, 3.1\u00a0\u00b1\u00a03.0; P\u00a0\u2264\u00a00.001), and a longer relapse-free interval (P\u00a0=\u00a00.004) compared with endoscopically treated patients. The overall complication rate was 32% both after surgery and endoscopy. Infectious-related complications occurred more often after surgical treatment (P\u00a0\u2264\u00a00.001), whereas patients after endoscopic intervention developed acute or chronic pancreatitis or pseudocyst formation (P\u00a0=\u00a00.023). CONCLUSIONS Patients who undergo surgery as their initial treatment for chronic pancreatitis require less consecutive interventions, a shorter hospital stay, and have a better quality of life compared with any other treatment. Surgery should therefore be considered early for the treatment of chronic pancreatitis, when endoscopic or conservative treatment fails and patients require further intervention.", "author" : [ { "dropping-particle" : "", "family" : "Rutter", "given" : "Karoline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferlitsch", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sautner", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "P\u00fcsp\u00f6k", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "G\u00f6tzinger", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gangl", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schindl", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "World journal of surgery", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2010", "11", "20" ] ] }, "page" : "2642-7", "title" : "Hospitalization, frequency of interventions, and quality of life after endoscopic, surgical, or conservative treatment in patients with chronic pancreatitis.", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(279)", "plainTextFormattedCitation" : "(279)", "previouslyFormattedCitation" : "(279)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(279) Retrospective150ND34LOE: very lowClarke (2012)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.cgh.2011.12.040", "ISSN" : "1542-7714", "PMID" : "22245964", "abstract" : "BACKGROUND & AIMS Endoscopic therapy (ET) frequently is used to treat patients with painful chronic pancreatitis (CP), but little is known about outcomes of patients for whom ET was not successful who then underwent surgery, or outcomes after ET compared with only medical treatment. We evaluated use and long-term effectiveness of ET in a well-defined cohort of patients with CP. METHODS We analyzed data from 146 patients with CP who participated in the North American Pancreatitis Study 2 at the University of Pittsburgh Medical Center from 2000 to 2006; 71 (49%) patients received ET at the University of Pittsburgh Medical Center. Success of ET and surgery were defined by cessation of narcotic therapy and resolution of episodes of acute pancreatitis. Disease progression was followed up from its onset until January 1, 2011 (mean, 8.2 \u00b1 4.7 y). RESULTS Patients who underwent ET had more symptoms (pain, recurrent pancreatitis) and had more complex pancreatic morphology (based on imaging) than patients who received medical therapy. ET had a high rate of technical success (60 of 71 cases; 85%); its rates of clinical success were 51% for 28 of 55 patients for whom follow-up data were available (mean time, 4.8 \u00b1 3.0 y) and 50% for 12 of 24 patients who underwent surgery after receiving ET. Patients who responded to ET were significantly older, had a shorter duration of disease before ET, had less constant pain, and required fewer daily narcotics than patients who did not respond to ET. Among the 36 symptomatic patients who received medical therapy and were followed up for a mean period of 5.7 \u00b1 4.1 years, 31% improved and 53% had no change in symptoms; of these, 21% underwent surgery. CONCLUSIONS ET is clinically successful for 50% of patients with symptomatic CP. When ET is not successful, surgery has successful outcomes in 50% of patients. Symptoms resolve in 31% of symptomatic patients who receive only medical therapy.", "author" : [ { "dropping-particle" : "", "family" : "Clarke", "given" : "Bridger", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slivka", "given" : "Adam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tomizawa", "given" : "Yutaka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanders", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Papachristou", "given" : "Georgios I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Whitcomb", "given" : "David C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yadav", "given" : "Dhiraj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2012", "7" ] ] }, "note" : "NULL", "page" : "795-802", "title" : "Endoscopic therapy is effective for patients with chronic pancreatitis.", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(253)", "plainTextFormattedCitation" : "(253)", "previouslyFormattedCitation" : "(253)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(253) Retrospective5551% (28 / 55)58Predictive factor of long-term responseLess constant painLess daily narcoticsShorter duration of diseaseLOE: lowHe (2014)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/MPA.0000000000000140", "ISSN" : "1536-4828", "PMID" : "24717828", "abstract" : "OBJECTIVE The aim of this study was to evaluate the M-ANNHEIM classification system to categorize patients with chronic pancreatitis (CP). METHODS All symptomatic patients recruited from the gastroenterology outpatient clinic of Changhai Hospital (n = 89) were routinely evaluated by magnetic resonance cholangiopancreatography and contrast-enhanced computed tomography. M-ANNHEIM clinical staging was used to categorize patients. The primary outcome measure was pain during the 2-year follow-up period, expressed as mean Izbicki pain scores obtained before and after endotherapy. RESULTS There was a significant improvement in mean (SD) Izbicki pain scores obtained at 24 months among patients receiving endoscopic therapy at stage 1a compared with those at stage 1b (4.9 [3.0] vs 14.5 [6.9], P = 0.012). Furthermore, significantly more patients receiving endoscopic therapy at stage 1a achieved complete + partial pain relief after 2-year follow-up than those at stage 1b (95.2% vs 78.0%, P = 0.021). There was no exocrine or endocrine insufficiency, but a significantly greater number of patients treated at stage 1a had post-endoscopic retrograde cholangiopancreatography pancreatitis compared with those at stage 1b (10.5% vs 2.7%, P = 0.025). CONCLUSIONS We demonstrated that a sophisticated M-ANNHEIM classification system for CP will improve diagnosis by allowing for more timely intervention. Furthermore, prompt treatment of CP may achieve improved pain relief and patient outcomes.", "author" : [ { "dropping-particle" : "", "family" : "He", "given" : "Yuan-Xiang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Hong-Wei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sun", "given" : "Xiao-Tian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ye", "given" : "Zhou", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Wei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lai", "given" : "Xiao-Wei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Xin-Tao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Liang-Hao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sun", "given" : "Chang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liao", "given" : "Zhuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Zhao-Shen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreas", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2014", "8" ] ] }, "note" : "NULL", "page" : "829-33", "title" : "Endoscopic management of early-stage chronic pancreatitis based on M-ANNHEIM classification system: a prospective study.", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(254)", "plainTextFormattedCitation" : "(254)", "previouslyFormattedCitation" : "(254)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(254) Prospective8981% (72 / 89)24LOE: lowTotal165778% (43 – 85)(1288 / 1657)Table 5 : SEMS in MPD for CPAuthor (year) (ref)DesignPopulationInterventionOutcomeCommentsEisendrath (1999)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1052-5157", "PMID" : "10390335", "abstract" : "Among patients with advanced chronic pancreatitis and morphologically demonstrable main pancreatic duct (MPD) abnormalities who are candidates for endotherapy, about two-thirds have a MPD stricture and require stenting to achieve appropriate ductal decompression. The standard stent used in this indication is the plastic stent, which provides a median patency rate of 6 to 12 months. The requirement for stent exchange represents a limitation for the treatment of this relatively young patient population. By analogy with the biliary tract, the authors hypothesize that self-expandable metal stents might offer a long-lasting drainage of the MPD. Several years ago the authors used such stents on an experimental basis to treat patients with MPD strictures. Although routine use of self-expandable metal stents should be discouraged, the authors propose some guidelines for further technical improvement.", "author" : [ { "dropping-particle" : "", "family" : "Eisendrath", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devi\u00e8re", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastrointestinal endoscopy clinics of North America", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "1999", "7" ] ] }, "note" : "NULL", "page" : "547-54", "title" : "Expandable metal stents for benign pancreatic duct obstruction.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(243)", "plainTextFormattedCitation" : "(243)", "previouslyFormattedCitation" : "(243)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(243)Retrospective observational38 patients:89% OHAge:42 y (n=20)38 y (n=18)Duration of disease: --Severe CP: --Pain: --FU (n=20): 70 mDiabetes: --Steatorrhea: --UC- SEMS: n=20PC (n=9) / FC (n=9) - SEMSTechnical success: 20/20 = 100% 16/18 = 89% (migration)Pain relief assessment: NAImmediate pain relief 20/20 = 100% 16/16 = 100%Sustained pain relief at 2 y 3/20 = 15% 4/16 = 25%Surgery: 2/38 = 5%LOE?: lowPark (2008)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.gie.2008.07.027", "ISSN" : "1097-6779", "PMID" : "19028228", "abstract" : "BACKGROUND Painful chronic pancreatitis with main pancreatic ductal strictures is usually managed with endotherapy with a plastic stent. To date, the role of placement of metallic stents, especially uncovered ones in benign pancreatic ductal stricture, has been unsatisfactory as a result of stent dysfunction related to mucosal hyperplasia. OBJECTIVE We explored the feasibility and safety of temporary placement of a newly designed, fully covered self-expandable metal stent (FCSEMS) in painful chronic pancreatitis and refractory benign pancreatic ductal strictures. DESIGN A prospective pilot and feasibility study. SETTING A tertiary academic center. PATIENTS Thirteen patients with chronic painful pancreatitis of alcoholic (8) or idiopathic (5) etiology. INTERVENTION ERCP with temporary FCSEMS placement (2 months). Endoscopic removal of FCSEMSs was performed with a snare or rat-tooth forceps. MAIN OUTCOME MEASUREMENTS End points were feasibility, safety, and morbidity. RESULTS Successful FCSEMS placement was performed in all enrolled patients. After immediate placement of FCSEMS, 2 patients had mild acute pancreatitis related mainly to the stricture dilation procedure (Soehendra stent retriever or balloon dilation). Complications associated with stent placement included 5 migrations (39%, 1 proximal and 4 distal) and 2 incidents of cholestatic liver dysfunction associated with the compression of the bile duct orifice by expansion of FCSEMSs. In 1 patient with proximal migration, the stent was repositioned by an inflated retrieval balloon. Additional endoscopic biliary sphincterotomy with or without biliary stenting was performed in 2 patients with cholestatic liver dysfunction. There was no occurrence of pancreatic sepsis among any patients. FCSEMSs were removed from 9 of 9 patients without stent migration (100% [9/9] as per protocol, and 69% [9/13] as intention to treat, respectively). Improvement or resolution of the pancreatic ductal strictures was confirmed in all 13 patients on follow-up ERCP (2 months after stent placement), regardless of stent migration. LIMITATIONS Small patient populations without long-term follow-up. CONCLUSIONS Two-month placement of FCSEMSs in patients with refractory benign pancreatic ductal strictures may be feasible and relatively safe. However, stent migration was not uncommon. A further investigation with ideal stent design may therefore be needed before recommending FCSEMSs as a therapeutic option for refractory benign pa\u2026", "author" : [ { "dropping-particle" : "", "family" : "Park", "given" : "Do Hyun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Myung-Hwan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moon", "given" : "Sung-Hoon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Sang Soo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seo", "given" : "Dong-Wan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Sung-Koo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastrointestinal endoscopy", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2008", "12" ] ] }, "note" : "NULL", "page" : "1182-9", "title" : "Feasibility and safety of placement of a newly designed, fully covered self-expandable metal stent for refractory benign pancreatic ductal strictures: a pilot study (with video).", "type" : "article-journal", "volume" : "68" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(244)", "plainTextFormattedCitation" : "(244)", "previouslyFormattedCitation" : "(244)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(244)Prospective pilot study13 patients:69% men, 62% OHAge: 51 yDuration of disease: --Severe CP: --Pain: 100%FU after stent removal: 5 mDiabetes: --Steatorrhea: --FC – SEMS (Niti D-type)Duration of stenting: 2 mTechnical success: 100%Pain relief assessment: NANo pain relapse during the 5 m FU after stent removalLOE?: lowSauer (2008)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.gie.2008.06.011", "ISSN" : "1097-6779", "PMID" : "19028226", "abstract" : "BACKGROUND Pancreatic duct (PD) stenting is beneficial for the treatment of pain in patients with PD strictures associated with chronic pancreatitis. Placement of metal stents has been reported but failed secondary to hyperplasia or migration. OBJECTIVE To investigate the outcome of patients with symptomatic and refractory PD strictures who had temporary placement of a covered self-expandable metal stent (CSEMS). DESIGN Patients with refractory PD strictures were offered temporary CSEMS placement. Pain scores were evaluated before and after CSEMS placement. SETTING A tertiary-care center. PATIENTS Six patients (4 men, mean age +/- SD 55 +/- 8 years) received a CSEMS, and 5 patients had removal of a CSEMS after a mean time of 92 days. INTERVENTION Placement of CSEMS (8-mm or 10-mm diameter VIABIL) in the PD, with removal after 3 months. MAIN OUTCOME MEASUREMENTS The pain score before and after stent placement and the sustained response after removal. Morbidity associated with stent placement and removal was also noted. RESULTS Pain scores after CSEMS placement significantly improved (P = .024), from 6.4 to 1.6. Of the 5 patients who underwent CSEMS removal, 3 developed recurrent symptomatic pancreatic stricture, of whom 2 required repeat stenting with a larger-diameter CSEMS (10 mm) and 2 remained pain free. The CSEMS was not removed in 1 patient because pancreatic malignancy was diagnosed. There were no complications during placement or removal of CSEMSs. LIMITATION This was a pilot study. CONCLUSION Temporary placement of CSEMSs in patients with symptomatic refractory PD stricture offers transient relief of pain. Further investigation is needed to determine the optimal diameter and duration of placement.", "author" : [ { "dropping-particle" : "", "family" : "Sauer", "given" : "Bryan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Talreja", "given" : "Jayant", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ellen", "given" : "Kristi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ku", "given" : "Jennifer", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shami", "given" : "Vanessa M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kahaleh", "given" : "Michel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastrointestinal endoscopy", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2008", "12" ] ] }, "note" : "NULL", "page" : "1173-8", "title" : "Temporary placement of a fully covered self-expandable metal stent in the pancreatic duct for management of symptomatic refractory chronic pancreatitis: preliminary data (with videos).", "type" : "article-journal", "volume" : "68" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(245)", "plainTextFormattedCitation" : "(245)", "previouslyFormattedCitation" : "(245)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(245)Prospective pilot study6 patients67% men, 67% OHAge: 55 yDuration of disease: --Severe CP: --Pain: 100%FU: --Diabetes: --Steatorrhea: --FC- SEMS (Viabil)EPS: 6/6, ESWL: 4/6Technical success: 100%Stent removal: 5/6 (1 pancreatic cancer)Duration of stenting: 3 mPain relief assessment- VAS before, 4 w after stent placement, 4 w after stent removalComplete pain relief: 2/5Recurrent symptomatic MPD stricture: 3/5Pain score improved: 4/6 (67%)LOE?: lowMoon (2010)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.gie.2010.01.063", "ISSN" : "1097-6779", "PMID" : "20493483", "abstract" : "BACKGROUND Fully covered self-expandable metal stent (FCSEMS) placement has recently been tried in the management of refractory pancreatic-duct strictures associated with advanced chronic pancreatitis. The major limitation of FCSEMSs was frequent migration. OBJECTIVE To assess the safety, migration rate, and removability of modified FCSEMSs with antimigration features used for the treatment of benign pancreatic-duct strictures. DESIGN Prospective study. SETTING Tertiary academic center. PATIENTS Thirty-two patients with chronic painful pancreatitis and dominant ductal stricture. INTERVENTIONS Transpapillary endoscopic placement of FCSEMSs in the pancreatic duct with removal after 3 months. MAIN OUTCOME MEASUREMENTS Technical and functional success and adverse events associated with the placement of metal stents. RESULTS FCSEMSs were successfully placed in all patients through the major (n = 27) or minor (n = 5) duodenal papilla. All patients achieved pain relief from stent placement. There was no occurrence of stent-induced pancreatitis or pancreatic sepsis. No stent migrated, and all stents were easily removed. Follow-up ERCP 3 months after stent placement showed resolution of duct strictures in all patients. Pancreatograms obtained at FCSEMS removal displayed de novo focal pancreatic duct strictures in 5 patients, but all were asymptomatic. LIMITATIONS No long-term follow-up. CONCLUSIONS Temporary 3-month placement of FCSEMSs was effective in resolving pancreatic-duct strictures in chronic pancreatitis, with an acceptable morbidity profile. Modified FCSEMSs can prevent stent migration, but may be associated with de novo duct strictures. Further trials are needed to assess long-term safety and efficacy.", "author" : [ { "dropping-particle" : "", "family" : "Moon", "given" : "Sung-Hoon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Myung-Hwan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Park", "given" : "Do Hyun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Song", "given" : "Tae Joon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eum", "given" : "Junbum", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Sang Soo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seo", "given" : "Dong Wan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Sung Koo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastrointestinal endoscopy", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2010", "7" ] ] }, "note" : "NULL", "page" : "86-91", "title" : "Modified fully covered self-expandable metal stents with antimigration features for benign pancreatic-duct strictures in advanced chronic pancreatitis, with a focus on the safety profile and reducing migration.", "type" : "article-journal", "volume" : "72" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(246)", "plainTextFormattedCitation" : "(246)", "previouslyFormattedCitation" : "(246)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(246)prospective32 patients:84% men, 59% OHAge: 48 yDuration of disease: --Severe CP: --Pain: --FU after stent removal: 5 mDiabetes: --Steatorrhea: --FC – SEMS (Niti-S, bumpy type), EPSESWL: 19/32 = 59%Technical success: 100%Duration of stenting: 3 mPain relief assessment: NARecurrent symptomatic stricture: 3/32 = 9%Complete pain relief: 27/32 = 84%Surgery: 1/32 = 3%LOE: lowGiacino (2012)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1055/s-0032-1309774", "ISSN" : "1438-8812", "PMID" : "22826158", "abstract" : "Fully covered self-expanding metal stents (FC-SEMSs), which can be removed from the bile duct, have recently been used in the main pancreatic duct (MPD) in chronic pancreatitis. The aim of this study was to investigate the feasibility, safety, and efficacy of FC-SEMSs in painful chronic pancreatitis with refractory pancreatic strictures. The primary endpoints were technical success and procedure-related morbidity. Secondary endpoints were pain relief at the end of follow-up and resolution of the dominant pancreatic stricture at endoscopic retrograde pancreatography. Over 5 months, 10 patients with painful chronic pancreatitis and refractory dominant pancreatic duct strictures were treated with FC-SEMSs. All FC-SEMSs were successfully released and removed, although two stents were embedded in the MPD at their distal end and treated endoscopically without complications. Mild abdominal pain was noted in three patients after stent release. During treatment, pain relief was achieved in nine patients, but one continued to take morphine, because of addiction. Cholestasis developed in two patients and was treated endoscopically; no patient developed acute pancreatitis or pancreatic sepsis. After stent removal, the diameter of the narrowest MPD stricture had increased significantly from 3.5 mm to 5.8 mm. Patients were followed up for a mean of 19.8 months: two patients who continued drinking alcohol presented with mild acute pancreatitis; one patient developed further chronic pancreatic pain; and one had a transient pain episode. At the end of the study, nine patients no longer had chronic pain and no patients had required surgery. Endoscopic treatment of refractory MPD stricture in chronic pancreatitis by placement of an FC-SEMS appears feasible, safe, and potentially effective.", "author" : [ { "dropping-particle" : "", "family" : "Giacino", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grandval", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laugier", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Endoscopy", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2012", "9", "23" ] ] }, "note" : "NULL", "page" : "874-7", "title" : "Fully covered self-expanding metal stents for refractory pancreatic duct strictures in chronic pancreatitis.", "type" : "article-journal", "volume" : "44" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(247)", "plainTextFormattedCitation" : "(247)", "previouslyFormattedCitation" : "(247)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(247)Case series10 patients:80% men, 60% OHAge: 55.7 yDuration of disease: --Severe CP: 100%Pain: 100%FU after stent removal: 20 mDiabetes: --Steatorrhea: --EPSFC – SEMS(1 biliary WST, 9 biliary WFX)Technical success: 100%Duration of stenting: 5.7 mPain relief assessment: NAComplete pain relief: 6/10 = 60%Partial pain relief: 3/10 = 30%Complete or partial pain relief: 90%Surgery: 0%LOE: lowTable 6 : ESWL aloneAuthor (year) (ref)DesignPopulationInterventionOutcomeCommentsOhara (1996)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0002-9270", "PMID" : "8678001", "abstract" : "OBJECTIVES We performed extracorporeal shock wave lithotripsy (ESWL) as the treatment of first choice on 32 chronic pancreatitis patients with main pancreatic duct (MPD) stones prospectively to establish more convenient and safer treatment. METHODS All patients were treated in a prone position, and shock waves were discharged from the ventral side. ESWL was performed once or twice a week, and no other treatments before ESWL had been applied. RESULTS Disintegration of all MPD stones to 3 mm or less in diameter could be achieved in all treated patients. Complete clearance of the stones was obtained in 24 patients (75%) without the necessity of endoscopic extraction of fragments. Reduction of MPD diameters after ESWL was statistically significant (p < 0.01). Epigastric and/or back pain complaints before ESWL were completely alleviated in 79% (periods of follow-up: 16-63 months, mean 44), and the pancreatic exocrine function also improved in 61%. No severe complications occurred in any of the patients. CONCLUSIONS ESWL, which is comparatively easy to perform, is a safe and efficient approach that changes endoscopy's status as an indispensable pretreatment. Therefore, ESWL can be recommended as the first choice treatment for patients with chronic pancreatitis accompanied by MPD stones that should be tried before consideration of either surgical or endoscopic procedures.", "author" : [ { "dropping-particle" : "", "family" : "Ohara", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoshino", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayakawa", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kamiya", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyaji", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takeuchi", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okayama", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gotoh", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American journal of gastroenterology", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "1996", "7" ] ] }, "note" : "NULL", "page" : "1388-94", "title" : "Single application extracorporeal shock wave lithotripsy is the first choice for patients with pancreatic duct stones.", "type" : "article-journal", "volume" : "91" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(262)", "plainTextFormattedCitation" : "(262)", "previouslyFormattedCitation" : "(262)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(262)Prospective observational32 patients:88% men, 88% OHAge: 57 yDuration of disease: --Severe CP: --Pain: 88%FU: 44 mDiabetes: --Steatorrhea: 6%ESWL alone (n=32)Pancreatic stenting: 0%Technical success: 79% (15/19)( MPD )Complete MPD clearance: 24/32 = 75%Pain relief assessment frequencyComplete pain relief: 22/28 = 79%Partial pain relief: 2/28 = 7%Complete or partial pain relief: 86%Need for ERCP: 3/32 = 9%Need for surgery: 1/32 = 3%Severe MPD stricture: 10/32 = 31%Steatorrhea: 2/32 = 6%No statistical analysisLOE?: lowInui (2005)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1536-4828", "PMID" : "15632696", "abstract" : "OBJECTIVES A retrospective multicenter survey was performed to evaluate the efficacy of extracorporeal shock wave lithotripsy (ESWL) as a treatment of pancreatic stones. METHODS A survey was sent to 11 institutions belonging to the Japanese Association of Extracorporeal Shock Wave Lithotripsy in Digestive Diseases, and data were collected on 555 patients who underwent ESWL for pancreatic stones between January 1990 and September 2002. The male:female ratio was 5.2:1, and the mean age was 52.5 years. The etiology was alcohol related in 425 patients (76.6%) and idiopathic in 111 patients (20.0%); 204 patients (36.8%) had a single stone and 470 patients (84.7%) were symptomatic. RESULTS Mean frequency of the procedure was 5.0 times (range, 1-29). Fragmentation of stones was achieved in 513 patients (92.4%), and the complete stone clearance rate after ESWL alone or in combination with interventional endoscopy was 72.6%. Symptom relief was achieved in 428 (91.1%) of 470 patients. Thirty-five patients (6.3%) developed complications, including 30 patients (5.4%) who developed acute pancreatitis. Five hundred four (90.8%) patients were followed for a mean of 44.3 months, during which 122 (22.0%) suffered stone recurrence (mean time to recurrence, 25.1 months). Twenty-two (4.1%) of the 504 patients who were followed required surgery. Pancreatic exocrine function improved in 65 patients (38.0%), was unchanged in 49 patients (28.7%), and progressed in 57 patients (33.3%). Pancreatic endocrine function improved in 44 patients (24.3%), was unchanged in 85 patients (47.0%), and progressed in 52 patients (28.7%). CONCLUSION ESWL is the treatment of choice for clearing pancreatic stones.", "author" : [ { "dropping-particle" : "", "family" : "Inui", "given" : "Kazuo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tazuma", "given" : "Susumu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamaguchi", "given" : "Taketo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ohara", "given" : "Hirotaka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsuji", "given" : "Tadao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyagawa", "given" : "Hiroyuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Igarashi", "given" : "Yoshinori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakamura", "given" : "Yuta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atomi", "given" : "Yutaka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreas", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2005", "1" ] ] }, "note" : "NULL", "page" : "26-30", "title" : "Treatment of pancreatic stones with extracorporeal shock wave lithotripsy: results of a multicenter survey.", "type" : "article-journal", "volume" : "30" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(263)", "plainTextFormattedCitation" : "(263)", "previouslyFormattedCitation" : "(263)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(263)Retrospective multicenter: 11 centers555 patients:84% men, 77% OHAge: 52.5 yDuration of disease: --Severe CP: --Pain: 85%FU (n=504): 44.3 mDiabetes: --Steatorrhea: --ESWL alone: n=318Spontaneous stone clearance: 222/318 = 70%No separate outcome for patients treated by ESWL aloneLOE?: lowDumonceau (2007)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/gut.2006.096883", "ISSN" : "0017-5749", "PMID" : "17047101", "abstract" : "BACKGROUND In chronic pancreatitis, obstruction of the main pancreatic duct (MPD) may contribute to the pathogenesis of pain. Pilot studies suggest that extracorporeal shock wave lithotripsy (ESWL) alone relieves pain in calcified chronic pancreatitis. AIM To compare ESWL alone with ESWL and endoscopic drainage of the MPD for treatment of pain in chronic pancreatitis. SUBJECTS Patients with uncomplicated painful chronic pancreatitis and calcifications obstructing the MPD. METHODS 55 patients were randomised to ESWL alone (n = 26) or ESWL combined with endoscopy (n = 29). RESULTS 2 years after trial intervention, 10 (38%) and 13 (45%) patients of the ESWL alone and ESWL combined with endoscopy group, respectively, had presented pain relapse (primary outcome) (OR 0.77; 95% CI 0.23 to 2.57). In both groups, a similar decrease was seen after treatment in the MPD diameter (mean decrease 1.7 mm; 95% CI 0.9 to 2.6; p<0.001), and in the number of pain episodes/year (mean decrease, 3.7; 95% CI 2.6 to 4.9; p<0.001). Treatment costs per patient were three times higher in the ESWL combined with endoscopy group compared with the ESWL alone group (p = 0.001). The median delay between the onset of chronic pancreatitis and persistent pain relief for both groups was 1.1 year (95% CI 0.7 to 1.6), as compared with 4 years (95% CI 3 to 4) for the natural history of chronic pancreatitis in a reference cohort (p<0.001). CONCLUSIONS ESWL is a safe and effective preferred treatment for selected patients with painful calcified chronic pancreatitis. Combining systematic endoscopy with ESWL adds to the cost of patient care, without improving the outcome of pancreatic pain.", "author" : [ { "dropping-particle" : "", "family" : "Dumonceau", "given" : "Jean-Marc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Costamagna", "given" : "Guido", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tringali", "given" : "Andrea", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vahedi", "given" : "Kouroche", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delhaye", "given" : "Myriam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hittelet", "given" : "Axel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spera", "given" : "Gianluca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giostra", "given" : "Emiliano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mutignani", "given" : "Massimiliano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maertelaer", "given" : "Viviane", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devi\u00e8re", "given" : "Jacques", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gut", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2007", "4", "1" ] ] }, "note" : "NULL", "page" : "545-52", "title" : "Treatment for painful calcified chronic pancreatitis: extracorporeal shock wave lithotripsy versus endoscopic treatment: a randomised controlled trial.", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(261)", "plainTextFormattedCitation" : "(261)", "previouslyFormattedCitation" : "(261)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(261)Prospective randomized trial26 patients85% men, 73% OHAge: 51.8 yDuration of disease: --Severe CP: 100%Pain: 100%(Type A: 62%)FU: 4.3 yDiabetes: 23%Steatorrhea: --ESWL alone: n=26Technical success: NAPain relief assessment- VAS (intensity)- number of pain episodes/yComplete pain relief- at 2 y: 16/26 = 62%- during whole FU at 4.3 y: 15/26 = 58%Need for ERCP: 8/26 = 31%Need for ESWL: 7/26 = 27%Need for surgery: 1/26 = 4%Factor independently associated with absence of pain relapse (whole series)-Location of obstructive calcification in the head of pancreas (p=0.013)Treatment costs per patient 3 times lower in the group ESWL alone compared to ESWL + endoscopyLOE?: highSuzuki (2013)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/MPA.0b013e31827308c8", "ISSN" : "1536-4828", "PMID" : "23558239", "abstract" : "OBJECTIVES A Japanese multicenter study of pancreatolithiasis was performed to investigate its clinical features and determine treatment strategies for pancreatolithiasis. METHODS A retrospective study was performed on 916 patients managed in 34 institutions for a period of more than 5 years. RESULTS The treatment methods were extracorporeal shock wave lithotripsy (ESWL) in 479 patients, surgery in 133, and endoscopy alone in 68. Fragmentation of stones after ESWL was achieved in 92.4% of the patients. However, complete stone clearance was achieved in 49.4% of the patients after ESWL alone. The complete stone clearance rate was lower after ESWL than after endoscopy (87.9%). The incidence of early complications was significantly higher after surgery (13.3%) than after ESWL (6.1%). The frequencies of total stone recurrence after ESWL (22.5%) and endoscopy (12.0%) were significantly higher than that after surgery (1.5%). After ESWL (17.6%), abdominal pain recurred significantly more frequently than after surgery (2.2%). Stones and abdominal pain most often recurred within 3 years after ESWL and endoscopy. CONCLUSIONS First-line treatment of pancreatic stones should be ESWL alone or with endoscopy because of its minimal invasiveness and low incidence of early complications. Surgery should be performed on patients in whom ESWL and endoscopy failed.", "author" : [ { "dropping-particle" : "", "family" : "Suzuki", "given" : "Yutaka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sugiyama", "given" : "Masanori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Inui", "given" : "Kazuo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Igarashi", "given" : "Yoshinori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ohara", "given" : "Hirotaka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tazuma", "given" : "Susumu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsuji", "given" : "Tadao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyakawa", "given" : "Hiroyuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atomi", "given" : "Yutaka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreas", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2013", "5" ] ] }, "note" : "NULL", "page" : "584-8", "title" : "Management for pancreatolithiasis: a Japanese multicenter study.", "type" : "article-journal", "volume" : "42" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(264)", "plainTextFormattedCitation" : "(264)", "previouslyFormattedCitation" : "(264)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(264)Retrospective multicenter: 34 centers202 patientsESWL aloneComplete MPD clearance: 49%No separate outcome for patients treated by ESWL aloneLOE: very lowList of Abbreviations in the TablesESWL?: extracorporeal shockwave lithotripsyFU?: follow-upy?: yearref : referenceCP?: chronic pancreatitisOH?: alcohol etiology of chronic pancreatitisEPS?: endoscopic pancreatic sphincterotomyMPD?: main pancreatic duct?: diameterVAS?: visual analogue scaleLOE?: level of evidencevery low: < 100 patients, retrospective, no assessment of pain relief, no statistical analysisLow: < 100 patients, retrospective or prospective, subjective or objective pain relief assessmentModerate: 100 patients, retrospective or prospective, objective pain relief assessmentHigh: RCT, 100 patients, prospective, objective pain relief assessment, identification of significant predictive factor of pain relief?: stone(s) fragmentationNA?: not availablem: monthND: not determinedITT: Intention To Treat analysisET: Endoscopical therapyAP: acute pancreatitis?: deadUS: ultrasonographyR: randomizedNR: non randomizedPD: pancreas divisumUC-SEMS: uncovered self expandable metal stentPC-SEMS: partially covered expandable metal stentFC-SEMS: fully covered expandable metal stentHarry van Goor, Tonya M Palermo & Eva SzigethyQ9. Are other treatments (neurolytical, psychological, ect.) effective for pain management in CP?Neurolytical interventions can be used in selected patients with painful CP who have failed endoscopic and surgical treatment. Thoracoscopic splanchnic denervation is more effective regarding long-term pain relief in patients who are not in chronic opioid treatment. Behavioral interventions should be part of the multidisciplinary approach in CP pain particularly when patients experience psychological impact of pain and quality of life has decreased. Early intervention in children may be particularly important.(Quality assessment: low, recommendation: strong; Agreement: conditional) This chapter comprises two different types of pain treatment in CP, nerve ablation (neurolytic) and psychological or psychiatric intervention. Consequences of CP in children and psychological treatments are addressed in a separate paragraph to create awareness for this small but underexposed group of patients with chronic pain. Overall the evidence of these types of treatments regarding pain relief is low due to lack of good quality trials. Neurolytic interventionsNeurolytical treatments of patients with chronic pancreatitis pain are generally implemented when other medical treatments have failed and patients are referred to pain specialist teams. Treatment is only recommended in patients not responding to conventional analgesics and/or having severe side effects of medication, in patients who have no pathology suitable for surgery or endoscopy or are not willing to undergo these treatments. Commonly this is done at a late disease stage when patients have suffered longstanding intractable pain, despite numerous treatments and are desperately seeking pain relief (‘last resort’). As a result, studies of nerve ablation interventions are predominantly done in populations of patients with severe chronic pancreatitis pain, are heterogenous, include fairly low quality trials, and often fail to demonstrate a long term beneficial effect. Finally, as a sham arm has never been used it is not known whether the effects are a result of the intervention per se or reflects the natural course of the disease.Neurolytical treatments can be at different levels of the visceral afferent system; celiac plexus block (percutaneous fluoroscopy or CT guided), surgical, endoscopic ultrasound (EUS) assisted), splanchnic nerve ablation (surgical, percutaneous). Other treatment (although not neurolytical) are stimulation of central parts in the brain (spinal cord and transcranial magnetic resonance (TMS) stimulation).Several techniques for percutaneous celiac plexus blockade have been describedADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s11916-013-0394-z", "ISSN" : "1534-3081", "PMID" : "24414338", "abstract" : "Chronic abdominal pain is a devastating problem for patients and providers, due to the difficulty of effectively treating the entity. Both benign and malignant conditions can lead to chronic abdominal pain. Precision in diagnosis is required before effective treatment can be instituted. Celiac Plexus Block is an interventional technique utilized for diagnostic and therapeutic purposes in the treatment of abdominovisceral pain. The richly innervated plexus provides sensory input about pathologic processes in the liver, pancreas, spleen, omentum, alimentary tract to the mid-transverse colon, adrenal glands, and kidney. Chronic pancreatitis and chronic pain from pancreatic cancer have been treated with celiac plexus block to theoretically decrease the side effects of opioid medications and to enhance analgesia from medications. Historically, the block was performed by palpation and identification of bony and soft tissue anatomy; currently, various imaging modalities are at the disposal of the interventionalist for the treatment of pain. Fluoroscopy, computed tomography (CT) guidance and endoscopic ultrasound assistance may be utilized to aid the practitioner in performing the blockade of the celiac plexus. The choice of radiographic technology depends on the specialty of the interventionalist, with gastroenterologists favoring endoscopic ultrasound and interventional pain physicians and radiologists preferring CT guidance. A review is presented describing the indications, technical aspects, and agents utilized to block the celiac plexus in patients suffering from chronic abdominal pain.", "author" : [ { "dropping-particle" : "V", "family" : "Rana", "given" : "Maunak", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Candido", "given" : "Kenneth D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raja", "given" : "Omar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Knezevic", "given" : "Nebojsa Nick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current pain and headache reports", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2014", "2", "11" ] ] }, "note" : "NULL", "page" : "394", "title" : "Celiac plexus block in the management of chronic abdominal pain.", "type" : "article-journal", "volume" : "18" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(281)", "plainTextFormattedCitation" : "(281)", "previouslyFormattedCitation" : "(281)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(281) but pain relief only lasts for several weeks to months and in about half of patients with no long term benefits. EUS-guided celiac plexus blockade was effective in alleviating abdominal pain in 51.46% of patients based on a systematic review of 6 studies comprising a total of 221 patientsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/MCG.0b013e3181bb854d", "ISSN" : "1539-2031", "PMID" : "19826273", "abstract" : "BACKGROUND/GOALS Endoscopic ultrasound (EUS)-guided celiac plexus block (CPB) and celiac plexus neurolysis (CPN) have become important interventions in the management of pain due to chronic pancreatitis and pancreatic cancer. However, only a few well-structured studies have been performed to evaluate their efficacy. Given limited data, their use remains controversial. Herein, we evaluate the efficacy of EUS-guided CPB and CPN in alleviating chronic abdominal pain due to chronic pancreatitis and pancreatic cancer respectively. STUDY METHODS Using Medline, Pubmed, and Embase databases from January 1966 through December 2007, a thorough search of the English literature for studies evaluating the efficacy of EUS-guided CPB and CPN for the management of chronic abdominal pain due to chronic pancreatitis and pancreatic cancer was conducted, along with a hand search of reference lists. Studies that involved less than 10 patients were excluded. Data on pain relief was extracted, pooled, and analyzed. RESULTS A total of 9 studies were included in the final analysis. For chronic pancreatitis, 6 relevant studies were identified, comprising a total of 221 patients. EUS-guided CPB was effective in alleviating abdominal pain in 51.46% of patients. For pancreatic cancer, 5 relevant studies were identified with a total of 119 patients. EUS-guided CPN was effective in alleviating abdominal pain in 72.54% of patients. CONCLUSIONS EUS-guided CPB was 51.46% effective in managing chronic abdominal pain in patients with chronic pancreatitis, but warrants improvement in patient selection and refinement of technique, whereas EUS-guided CPN was 72.54% effective in managing pain due to pancreatic cancer and is a reasonable option for patients with tolerance to narcotic analgesics.", "author" : [ { "dropping-particle" : "", "family" : "Kaufman", "given" : "Marina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Gurpreet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Das", "given" : "Sourish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Concha-Parra", "given" : "Ronald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erber", "given" : "Jonathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Micames", "given" : "Carlos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gress", "given" : "Frank", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of clinical gastroenterology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2010", "2" ] ] }, "note" : "NULL", "page" : "127-34", "title" : "Efficacy of endoscopic ultrasound-guided celiac plexus block and celiac plexus neurolysis for managing abdominal pain associated with chronic pancreatitis and pancreatic cancer.", "type" : "article-journal", "volume" : "44" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(282)", "plainTextFormattedCitation" : "(282)", "previouslyFormattedCitation" : "(282)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(282). Although endoscopic ultrasonore guided plexus block was superior to percutaneous CT guided block in 2 RCTs regarding duration of pain relief, long term pain relief was insufficient or not investigatedADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nrgastro.2014.74", "ISSN" : "1759-5053", "PMID" : "24912390", "abstract" : "This Review covers the latest developments in the treatment options for chronic pancreatitis. Pain is the most frequent and dominant symptom in patients with chronic pancreatitis, which ranges from severe disabling continuous pain to mild pain attacks and pain-free periods. Conventional treatment strategies and recent changes in the treatment of pain in patients with chronic pancreatitis are outlined. The different treatment options for pain consist of medical therapy, endoscopy or surgery. Their related merits and drawbacks are discussed. Finally, novel insights in the field of genetics and microbiota are summarized, and future perspectives are discussed.", "author" : [ { "dropping-particle" : "", "family" : "Issa", "given" : "Yama", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruno", "given" : "Marco J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bakker", "given" : "Olaf J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Besselink", "given" : "Marc G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schepers", "given" : "Nicolien J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Santvoort", "given" : "Hjalmar C", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gooszen", "given" : "Hein G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boermeester", "given" : "Marja A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature reviews. Gastroenterology & hepatology", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2014", "9", "10" ] ] }, "note" : "NULL", "page" : "556-64", "title" : "Treatment options for chronic pancreatitis.", "type" : "article-journal", "volume" : "11" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(283)", "plainTextFormattedCitation" : "(283)", "previouslyFormattedCitation" : "(283)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(283). Furthermore, there is a risk for side effects such as postural hypotension and diarrhea. After a short-lived period of use, endoscopic ultrasonore guided celiac plexus block is nowadays rarely applied.Thoracoscopic splanchnicectomy was first described as minimally invasive therapy for pain in 1994ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0035-8835", "PMID" : "7515430", "abstract" : "The technique of bilateral total splanchnicectomy performed through a posterior thoracoscopic approach is described. The advantages of this route include excellent visual exposure of the neural anatomy of the sympathetic and avoidance of single lung anaesthesia. The procedure was performed for the relief of intractable pain in patients with advanced pancreatic cancer (n = 3) and patients suffering from chronic pancreatitis (n = 5). Persistent relief of pain until death was obtained in the patients with pancreatic cancer (2, 4, 6 months). In patients with chronic pancreatitis, the benefit to date has varied with the severity of the disease. In two patients with severe advanced disease and previous percutaneous blocks, the relief of pain lasted only 3 and 5 weeks and both patients required resection for renewed intractable pain. In three patients with minimal change disease, relief of pain has been good in the short term (maximum follow-up of 8 months). Bilateral thoracoscopic total splanchnicectomy merits further evaluation in patients with pancreatic pain. No complications including hypotension have been encountered.", "author" : [ { "dropping-particle" : "", "family" : "Cuschieri", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shimi", "given" : "S M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crosthwaite", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Joypaul", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of the Royal College of Surgeons of Edinburgh", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "1994", "2" ] ] }, "note" : "NULL", "page" : "44-7", "title" : "Bilateral endoscopic splanchnicectomy through a posterior thoracoscopic approach.", "type" : "article-journal", "volume" : "39" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(284)", "plainTextFormattedCitation" : "(284)", "previouslyFormattedCitation" : "(284)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(284) and has been researched by several groups in the world since then; however, to date no RCT has been done. In a recent review of sixteen studies with 484 patients with thoracoscopic splanchnicectomy and a minimum follow-up of 12 months, a median of 49% of patients were free of opioids at end of follow-upADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nrgastro.2014.74", "ISSN" : "1759-5053", "PMID" : "24912390", "abstract" : "This Review covers the latest developments in the treatment options for chronic pancreatitis. Pain is the most frequent and dominant symptom in patients with chronic pancreatitis, which ranges from severe disabling continuous pain to mild pain attacks and pain-free periods. Conventional treatment strategies and recent changes in the treatment of pain in patients with chronic pancreatitis are outlined. The different treatment options for pain consist of medical therapy, endoscopy or surgery. Their related merits and drawbacks are discussed. Finally, novel insights in the field of genetics and microbiota are summarized, and future perspectives are discussed.", "author" : [ { "dropping-particle" : "", "family" : "Issa", "given" : "Yama", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruno", "given" : "Marco J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bakker", "given" : "Olaf J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Besselink", "given" : "Marc G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schepers", "given" : "Nicolien J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Santvoort", "given" : "Hjalmar C", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gooszen", "given" : "Hein G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boermeester", "given" : "Marja A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature reviews. Gastroenterology & hepatology", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2014", "9", "10" ] ] }, "note" : "NULL", "page" : "556-64", "title" : "Treatment options for chronic pancreatitis.", "type" : "article-journal", "volume" : "11" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(283)", "plainTextFormattedCitation" : "(283)", "previouslyFormattedCitation" : "(283)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(283). Similar to pancreatic surgery for chronic pancreatitis, preoperative opioid use and duration of disease and pain seem to impair long term results probably due to central sensitizationADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/AAP.0b013e31822e0d4a", "ISSN" : "1532-8651", "PMID" : "22005656", "abstract" : "BACKGROUND AND OBJECTIVES Central sensitization due to visceral pancreatic nociceptive input may be important in chronic pancreatitis pain. We investigated whether bilateral thoracoscopic splanchnicectomy (BTS) to reduce nociceptive input in chronic pancreatitis patients (CPP) with poor pain control affects supraspinal and spinal sensitization. METHODS Seventeen CPP were studied preoperatively and 6 weeks after BTS. Pressure pain thresholds (PPT) were measured in clavicle and pancreatic dermatomes reflecting supraspinal and spinal central sensitization, respectively. Patients with increased PPT after BTS (hypoalgesic) were compared to those without (hyperalgesic) and PPT vs. pain numeric rating scale (NRS) changes compared. RESULTS After BTS, ten patients showed C5 PPT increases (hypoalgesic; median change 87 kPa), 7 patients had unaltered/lower PPT (hyperalgesic; -135 kPa). Preoperative pain NRS was similar between groups (4 vs. 5, P = 0.2). After BTS hypoalgesic group NRS was lower (1 vs. 6; P = 0.008) and NRS change greater (-2 vs. 0; P = 0.005). Whole group NRS and C5 PPT change correlated significantly and negatively (r = 0.53; P < 0.05), but not for pancreatic PPT. CONCLUSIONS Reduced supraspinal-but not spinal-central sensitization after BTS was associated with significantly reduced pain scores in a majority of CPP. A subgroup showed no reductions in supraspinal central sensitization after BTS, coupled to no significant pain NRS reduction. Our results suggest that a subgroup of CPP has altered pain processing that may be independent of ongoing peripheral nociceptive input, resulting in persisting pain despite BTS. If confirmed, these results indicate the importance of sensory testing for indications and management of pain treatments.", "author" : [ { "dropping-particle" : "", "family" : "Bouwense", "given" : "Stefan A W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buscher", "given" : "Hessel C J L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goor", "given" : "Harry", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "Oliver H G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Regional anesthesia and pain medicine", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2011", "11" ] ] }, "note" : "NULL", "page" : "531-6", "title" : "Has central sensitization become independent of nociceptive input in chronic pancreatitis patients who fail thoracoscopic splanchnicectomy?", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(285)", "plainTextFormattedCitation" : "(285)", "previouslyFormattedCitation" : "(285)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(285). Splanchnicectomy early in the disease course and before opioids are started could be an attractive alternative to early pancreatic surgery, but this needs to be further researched in a trial. Even less invasive is percutaneous splanchnic nerve radiofrequency ablation. Only retrospective small series are reported with good effects, however, for a short periodADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/papr.12030", "ISSN" : "1533-2500", "PMID" : "23301539", "abstract" : "BACKGROUND Pain is a major problem for chronic pancreatitis (CP) patients. Unfortunately, medical therapy often fails. Endoscopic and surgical treatments are invasive, and results vary. Percutaneous radiofrequency ablation of the splanchnic nerves (RFSN) is a relatively new and minimally invasive procedure for treatment of intractable pain in CP patients. MATERIALS AND METHODS We retrospectively evaluated 18 RFSN procedures in 11 CP patients, all refractory to analgesics. Five patients underwent a second procedure; two patients underwent a third procedure. NRS pain scores were assessed. Complications, analgesics usage, and length of the pain-free period were recorded. RESULTS Radiofrequency ablation of the splanchnic nerves was effective in 15/18 interventions. The mean NRS pain score decreased from 7.7\u00a0\u00b1\u00a01.0 to 2.8\u00a0\u00b1\u00a02.7 (P\u00a0\u2264\u00a00.001). The pain-free period lasted for a median period of 45\u00a0weeks. The effect of repeated interventions was comparable to the initial procedure. One transient side effect was reported. Four patients reported significantly reduced analgesic usage; 4 patients completely stopped their pain medication. CONCLUSION Radiofrequency ablation of the splanchnic nerves is a minimally invasive, effective procedure for pain relief. After the effect has subsided, RFSN can be successfully repeated. RFSN might become an alternative treatment in a selected group of CP patients. A larger, randomized trial is justified to substantiate these findings.", "author" : [ { "dropping-particle" : "", "family" : "Verhaegh", "given" : "Bas P M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kleef", "given" : "Maarten", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Geurts", "given" : "Jos\u00e9 W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Puylaert", "given" : "Martine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zundert", "given" : "Jan", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kessels", "given" : "Alphons G H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Masclee", "given" : "Ad A M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keulemans", "given" : "Yolande C A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pain practice : the official journal of World Institute of Pain", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2013", "11" ] ] }, "note" : "NULL", "page" : "621-6", "title" : "Percutaneous radiofrequency ablation of the splanchnic nerves in patients with chronic pancreatitis: results of single and repeated procedures in 11 patients.", "type" : "article-journal", "volume" : "13" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(286)", "plainTextFormattedCitation" : "(286)", "previouslyFormattedCitation" : "(286)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(286). Advantage of this technique is the possibility to repeat the ablation without much morbidity.There are only a few retrospective studies of spinal cord stimulation and case reports in transcranial magnetic stimulation (TMS) in chronic pancreatitisADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1525-1403.2011.00381.x", "ISSN" : "1525-1403", "PMID" : "21854493", "abstract" : "BACKGROUND AND OBJECTIVES \u2002 Spinal cord stimulation (SCS) may reduce pain scores and improve function in patients with various chronic abdominal pain syndromes including chronic pancreatitis. Here described is a large clinical experience in SCS for severe chronic pancreatitis. METHODS \u2002 SCS was trialed in 30 patients with chronic pancreatitis. SCS trials lasted 7-14 days (median 9 days). SCS lead tips were mostly positioned at the T5 (N= 10) or T6 (N= 10) vertebral level. RESULTS \u2002 Twenty-four patients (80%) reported at least 50% pain relief on completion of the trial. Among these, pre-trial visual analog scale (VAS) pain scores averaged 8 \u00b1 1.6 (standard deviation) and opioid use averaged 165 \u00b1 120 mg morphine sulfate equivalents. During the trial, VAS pain scores decreased to 3.67 \u00b1 2 cm (p < 0.001, Mann-Whitney Rank Sum Test) and opioid use decreased to 105 \u00b1 101 mg morphine equivalent a day. Six patients failed the trial; one was lost to follow-up; in three patients after the implantation, the system had to be removed due to infection or lead migration; and 20 were followed for the whole year. For 20 patients followed for the whole year, VAS pain scores remained low (3.6 \u00b1 2 cm; p < 0.001) at one year, as did opioid use (48.6 \u00b1 58 mg morphine equivalents). CONCLUSIONS \u2002 SCS may be a useful therapeutic option for patients with severe visceral pain from chronic pancreatitis. Prospective trial is warranted.", "author" : [ { "dropping-particle" : "", "family" : "Kapural", "given" : "Leonardo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cywinski", "given" : "Jacek B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sparks", "given" : "Dawn A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Neuromodulation : journal of the International Neuromodulation Society", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2011", "9" ] ] }, "note" : "NULL", "page" : "423-6; discussion 426-7", "title" : "Spinal cord stimulation for visceral pain from chronic pancreatitis.", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.ejpain.2010.08.002", "ISSN" : "1532-2149", "PMID" : "20822942", "abstract" : "BACKGROUND AND AIMS Chronic visceral pain is frequent, extremely debilitating, and generally resistant to pharmacological treatment. It has been shown that chronic visceral inflammation, through altered afferent visceral sensory input, leads to plastic changes in the central nervous system that ultimately sustain pain. Therefore approaches aiming at modulation of brain activity are attractive candidates to control visceral pain. METHODS Here we report findings of a phase II, sham-controlled clinical trial assessing the clinical effects and brain metabolic correlates of a 10-day course of daily sessions of slow-frequency, repetitive transcranial magnetic stimulation (rTMS) targeting the right secondary somatosensory cortex (SII) in patients with chronic pancreatitis and severe visceral pain. RESULTS Our results show a significant reduction in pain after real rTMS that lasted for at least 3 weeks following treatment. These clinical changes were correlated with increases in glutamate and N-acetyl aspartate (NAA) levels--neurometabolites associated with cortical activity and brain damage--as measured by in vivo single-voxel proton magnetic resonance spectroscopy (1H-MRS). Adverse effects in the real rTMS group were mild and short-lasting. CONCLUSIONS Our results support preliminary findings showing that modulation of right SII with rTMS is associated with a significant analgesic effect and that this effect is correlated with an increase in excitatory neurotransmitter levels such as glutamate and NAA.", "author" : [ { "dropping-particle" : "", "family" : "Fregni", "given" : "Felipe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Potvin", "given" : "Kimberly", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dasilva", "given" : "Deborah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Xiaoen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lenkinski", "given" : "Robert E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freedman", "given" : "Steven D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pascual-Leone", "given" : "Alvaro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European journal of pain (London, England)", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2011", "1" ] ] }, "note" : "NULL", "page" : "53-60", "title" : "Clinical effects and brain metabolic correlates in non-invasive cortical neuromodulation for visceral pain.", "type" : "article-journal", "volume" : "15" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(287,288)", "plainTextFormattedCitation" : "(287,288)", "previouslyFormattedCitation" : "(287,288)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(287,288). Pain relief for more than a year was achieved in 66 percent of patients with severe chronic pancreatitis who had spinal cord stimulation. Drawback of the procedure is the invasiveness and potential for implant infectionADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1525-1403.2011.00381.x", "ISSN" : "1525-1403", "PMID" : "21854493", "abstract" : "BACKGROUND AND OBJECTIVES \u2002 Spinal cord stimulation (SCS) may reduce pain scores and improve function in patients with various chronic abdominal pain syndromes including chronic pancreatitis. Here described is a large clinical experience in SCS for severe chronic pancreatitis. METHODS \u2002 SCS was trialed in 30 patients with chronic pancreatitis. SCS trials lasted 7-14 days (median 9 days). SCS lead tips were mostly positioned at the T5 (N= 10) or T6 (N= 10) vertebral level. RESULTS \u2002 Twenty-four patients (80%) reported at least 50% pain relief on completion of the trial. Among these, pre-trial visual analog scale (VAS) pain scores averaged 8 \u00b1 1.6 (standard deviation) and opioid use averaged 165 \u00b1 120 mg morphine sulfate equivalents. During the trial, VAS pain scores decreased to 3.67 \u00b1 2 cm (p < 0.001, Mann-Whitney Rank Sum Test) and opioid use decreased to 105 \u00b1 101 mg morphine equivalent a day. Six patients failed the trial; one was lost to follow-up; in three patients after the implantation, the system had to be removed due to infection or lead migration; and 20 were followed for the whole year. For 20 patients followed for the whole year, VAS pain scores remained low (3.6 \u00b1 2 cm; p < 0.001) at one year, as did opioid use (48.6 \u00b1 58 mg morphine equivalents). CONCLUSIONS \u2002 SCS may be a useful therapeutic option for patients with severe visceral pain from chronic pancreatitis. Prospective trial is warranted.", "author" : [ { "dropping-particle" : "", "family" : "Kapural", "given" : "Leonardo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cywinski", "given" : "Jacek B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sparks", "given" : "Dawn A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Neuromodulation : journal of the International Neuromodulation Society", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2011", "9" ] ] }, "note" : "NULL", "page" : "423-6; discussion 426-7", "title" : "Spinal cord stimulation for visceral pain from chronic pancreatitis.", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(287)", "plainTextFormattedCitation" : "(287)", "previouslyFormattedCitation" : "(287)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(287). Repetitive TMS holds promise for treating depression in chronic pancreatitis patients with a possible concurrent pain relieving effect, but this needs to be investigated in more homogenous groups of patients and with validated techniques. Psychological/psychiatric interventionsPain in CP is multi-determined and underlying etiology is not well delineated though features of nociceptive, visceral, neuropathic and central mechanisms have been implicated. In other disease populations, chronic non-cancer pain is associated with depression-anxiety spectrum disordersADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jpain.2008.05.005", "ISSN" : "1528-8447", "PMID" : "18602869", "abstract" : "UNLABELLED Although there is a growing body of research concerning the prevalence and correlates of chronic pain conditions and their association with mental disorders, cross-national research on age and gender differences is limited. The present study reports the prevalence by age and gender of common chronic pain conditions (headache, back or neck pain, arthritis or joint pain, and other chronic pain) in 10 developed and 7 developing countries and their association with the spectrum of both depressive and anxiety disorders. It draws on data from 18 general adult population surveys using a common survey questionnaire (N = 42,249). Results show that age-standardized prevalence of chronic pain conditions in the previous 12 months was 37.3% in developed countries and 41.1% in developing countries, with back pain and headache being somewhat more common in developing than developed countries. After controlling for comorbid chronic physical diseases, several findings were consistent across developing and developed countries. There was a higher prevalence of chronic pain conditions among females and older persons; and chronic pain was similarly associated with depression-anxiety spectrum disorders in developed and developing countries. However, the large majority of persons reporting chronic pain did not meet criteria for depression or anxiety disorder. We conclude that common pain conditions affect a large percentage of persons in both developed and developing countries. PERSPECTIVE Chronic pain conditions are common in both developed and developing countries. Overall, the prevalence of pain is greater among females and among older persons. Although most persons reporting pain do not meet criteria for a depressive or anxiety disorder, depression/anxiety spectrum disorders are associated with pain in both developed and developing countries.", "author" : [ { "dropping-particle" : "", "family" : "Tsang", "given" : "Adley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Korff", "given" : "Michael", "non-dropping-particle" : "Von", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Sing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alonso", "given" : "Jordi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karam", "given" : "Elie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Angermeyer", "given" : "Matthias C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borges", "given" : "Guilherme Luiz Guimaraes", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bromet", "given" : "Evelyn J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Demytteneare", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Girolamo", "given" : "Giovanni", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graaf", "given" : "Ron", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gureje", "given" : "Oye", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lepine", "given" : "Jean-Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haro", "given" : "Josep Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Levinson", "given" : "Daphna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oakley Browne", "given" : "Mark A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Posada-Villa", "given" : "Jose", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seedat", "given" : "Soraya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Makoto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The journal of pain : official journal of the American Pain Society", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2008", "10" ] ] }, "note" : "NULL", "page" : "883-91", "title" : "Common chronic pain conditions in developed and developing countries: gender and age differences and comorbidity with depression-anxiety disorders.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0304-3959", "PMID" : "14581119", "abstract" : "Chronic pain and psychiatric disorders frequently co-occur. However, estimates of the magnitude of these associations have been biased by the use of select clinical samples. The present study utilized the National Comorbidity Survey [Arch. Gen. Psychiatry 51 (1994) 8-19] Part II data set to investigate the associations between a chronic pain condition (i.e. arthritis) and common mood and anxiety disorders in a sample representative of the general US civilian population. Participants (N=5877) completed the Composite International Diagnostic Interview [World Health Organization (1990)], a structured interview for trained non-clinician interviewers based on the revised third edition of the Diagnostic and Statistical Manual of Mental Disorders [American Psychiatric Association (1987)], and provided self-reports of pain and disability associated with a variety of medical conditions. Significant positive associations were found between chronic pain and individual 12-month mood and anxiety disorders [odds ratios (OR) ranged from 1.92 to 4.27]. The strongest associations were observed with panic disorder (OR=4.27) and post-traumatic stress disorder (OR=3.69). The presence of one psychiatric disorder was not significantly associated with pain-related disability, but the presence of multiple psychiatric disorders was significantly associated with increased disability. The findings of the present study raise the possibility that improved efforts regarding the detection and treatment of anxiety disorders may be required in pain treatment settings.", "author" : [ { "dropping-particle" : "", "family" : "McWilliams", "given" : "Lachlan A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cox", "given" : "Brian J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Enns", "given" : "Murray W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pain", "id" : "ITEM-2", "issue" : "1-2", "issued" : { "date-parts" : [ [ "2003", "11" ] ] }, "note" : "NULL", "page" : "127-33", "title" : "Mood and anxiety disorders associated with chronic pain: an examination in a nationally representative sample.", "type" : "article-journal", "volume" : "106" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.jpsychires.2009.10.013", "ISSN" : "1879-1379", "PMID" : "20149391", "abstract" : "This study aims (1) to assess the prevalence of Chronic Painful Physical Condition (CPPC) and major depressive disorder (MDD) in the general population; (2) to evaluate their interaction and co-morbidity with sleep and organic disorders; and (3) to investigate their daily functioning and socio-professional consequences. A random sample of 3243 subjects (18years), representative of California inhabitants, was interviewed by telephone. CPPC duration was at least 6months. Frequency, severity, duration and consequences on daily functioning, consultations, sick leave and treatment were investigated. MDD were assessed using DSM-IV criteria. The point prevalence of CPPC was 49% (95% confidence interval: 47.0-51.0%). Back area pain was the most frequent; 1-month prevalence of MDD was at 6.3% (95% CI: 5.5-7.2%); 66.3% of MDD subjects reported at least one CPPC. In 57.1% of cases, pain appeared before MDD. Pain severity was increased by poor sleep, stress and tiredness in MDD subjects. Being confined to bed, taking sick leave and interference of pain with daily functioning were twice as frequent among MDD subjects with CPPC than in non-MDD subjects with CPPC; obese individuals with CP were 2.6 times as likely to have MDD. Pain is highly linked with depressive disorder. It deteriorates physical, occupational and socio-professional activities. Pain and sleep disturbances are a prime motive of consultation rather than depressed mood, underlining the risk of missing a depression diagnosis.", "author" : [ { "dropping-particle" : "", "family" : "Ohayon", "given" : "Maurice M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schatzberg", "given" : "Alan F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of psychiatric research", "id" : "ITEM-3", "issue" : "7", "issued" : { "date-parts" : [ [ "2010", "5" ] ] }, "note" : "NULL", "page" : "454-61", "title" : "Chronic pain and major depressive disorder in the general population.", "type" : "article-journal", "volume" : "44" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(289\u2013291)", "plainTextFormattedCitation" : "(289\u2013291)", "previouslyFormattedCitation" : "(289\u2013291)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(289–291) and substance misuse or abuseADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/01.psy.0000204851.15499.fc", "ISSN" : "1534-7796", "PMID" : "16554392", "abstract" : "OBJECTIVES The objectives of this study were to provide estimates of the prevalence and strength of association between major depression and chronic pain in a primary care population and to examine the clinical burden associated with the two conditions, singly and together. METHODS A random sample of Kaiser Permanente patients who visited a primary care clinic was mailed a questionnaire assessing major depressive disorder (MDD), chronic pain, pain-related disability, somatic symptom severity, panic disorder, other anxiety, probable alcohol abuse, and health-related quality of life (HRQL). Instruments included the Patient Health Questionnaire, SF-8, and Graded Chronic Pain Questionnaire. A total of 5808 patients responded (54% of those eligible to participate). RESULTS Among those with MDD, a significantly higher proportion reported chronic (i.e., nondisabling or disabling) pain than those without MDD (66% versus 43%, respectively). Disabling chronic pain was present in 41% of those with MDD versus 10% of those without MDD. Respondents with comorbid depression and disabling chronic pain had significantly poorer HRQL, greater somatic symptom severity, and higher prevalence of panic disorder than other respondents. The prevalence of probable alcohol abuse/dependence was significantly higher among persons with MDD compared with individuals without MDD regardless of pain or disability level. Compared with participants without MDD, the prevalence of other anxiety among those with MDD was more than sixfold greater regardless of pain or disability level. CONCLUSIONS Chronic pain is common among those with MDD. Comorbid MDD and disabling chronic pain are associated with greater clinical burden than MDD alone.", "author" : [ { "dropping-particle" : "", "family" : "Arnow", "given" : "Bruce A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hunkeler", "given" : "Enid M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blasey", "given" : "Christine M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Janelle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Constantino", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fireman", "given" : "Bruce", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kraemer", "given" : "Helena C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dea", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Robinson", "given" : "Rebecca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayward", "given" : "Chris", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychosomatic medicine", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2006", "3" ] ] }, "note" : "NULL", "page" : "262-8", "title" : "Comorbid depression, chronic pain, and disability in primary care.", "type" : "article-journal", "volume" : "68" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1097/ALN.0000000000000768", "ISSN" : "0003-3022", "PMID" : "26375824", "abstract" : "BACKGROUND Opioids are frequently prescribed for chronic low back pain (CLBP), but there are little prospective data on which patient subgroups may benefit. Psychiatric comorbidity, such as high levels of depression and anxiety symptoms (termed comorbid negative affect [NA]), is a common presentation and may predict diminished opioid analgesia and/or increased opioid misuse. METHODS The authors conducted a 6\u00bd-month prospective cohort study of oral opioid therapy, with an active drug/placebo run-in period, in 81 CLBP patients with low, moderate, and high levels of NA. Treatment included an opioid titration phase with a prescribing physician blinded to NA group assignment and a 4-month continuation phase, during which subjects recorded daily pain levels using an electronic diary. The primary outcome was the percent improvement in average daily pain, summarized weekly. RESULTS There was an overall 25% dropout rate. Despite the high NA group being prescribed a higher average daily dose of morphine equivalents, linear mixed model analysis revealed that the 24 study completers in each of the high NA and low NA groups had an average 21 versus 39% improvement in pain, respectively (P < 0.01). The high NA group also had a significantly greater rate of opioid misuse (39 vs. 8%, P < 0.05) and significantly more and intense opioid side effects (P < 0.01). CONCLUSIONS These results indicate that the benefit and risk considerations in CLBP patients with high NA versus low NA are distinctly different. Thus, NA is an important phenotypic variable to characterize at baseline, before deciding whether to prescribe opioids for CLBP.", "author" : [ { "dropping-particle" : "", "family" : "Wasan", "given" : "Ajay D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Michna", "given" : "Edward", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Edwards", "given" : "Robert R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katz", "given" : "Jeffrey N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nedeljkovic", "given" : "Srdjan S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dolman", "given" : "Andrew J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Janfaza", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Isaac", "given" : "Zach", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jamison", "given" : "Robert N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Anesthesiology", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2015", "10" ] ] }, "note" : "NULL", "page" : "861-872", "title" : "Psychiatric Comorbidity Is Associated Prospectively with Diminished Opioid Analgesia and Increased Opioid Misuse in Patients with Chronic Low Back Pain", "type" : "article-journal", "volume" : "123" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(292,293)", "plainTextFormattedCitation" : "(292,293)", "previouslyFormattedCitation" : "(292,293)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(292,293), which if unaddressed, can further complicate treatment of pain. Post-traumatic stress disorder is also associated with chronic pain ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Fishbain DA, Pulikal A", "given" : "Lewis JE et al.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pain Med", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "title" : "Chronic Pain Types Differ in Their Reported Prevalence of Post -Traumatic Stress Disorder (PTSD) and There Is Consistent Evidence That Chronic Pain Is Associated with PTSD: An Evidence-Based Structured Systematic Review", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1177/070674370204701004", "ISSN" : "0706-7437", "PMID" : "12553128", "abstract" : "It is common for individuals with symptoms of posttraumatic stress disorder (PTSD) to present with co-occurring pain problems, and vice versa. However, the relation between these conditions often goes unrecognized in clinical settings. In this paper, we describe potential relations between PTSD and chronic pain and their implications for assessment and treatment. To accomplish this, we discuss phenomenological similarities of these conditions, the prevalence of chronic pain in patients with PTSD, and the prevalence of PTSD in patients with chronic pain. We also present several possible explanations for the co-occurrence of these disorders, based primarily on the notions of shared vulnerability and mutual maintenance. The paper concludes with an overview of future research directions, as well as practical recommendations for assessing and treating patients who present with co-occurring PTSD or chronic pain symptoms.", "author" : [ { "dropping-particle" : "", "family" : "Asmundson", "given" : "Gordon J G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Coons", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Taylor", "given" : "Steven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katz", "given" : "Joel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Canadian journal of psychiatry. Revue canadienne de psychiatrie", "id" : "ITEM-2", "issue" : "10", "issued" : { "date-parts" : [ [ "2002", "12" ] ] }, "note" : "NULL", "page" : "930-7", "title" : "PTSD and the experience of pain: research and clinical implications of shared vulnerability and mutual maintenance models.", "type" : "article-journal", "volume" : "47" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(294,295)", "plainTextFormattedCitation" : "(294,295)", "previouslyFormattedCitation" : "(294,295)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(294,295). Consistent with common psychosocial impact experienced by other patients with chronic pain, patients with CP also report high rates of depression, substance use, and poor quality of lifeADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1155/2012/978646", "ISSN" : "2090-1550", "PMID" : "23227332", "abstract" : "Objective. The present study was conducted to determine if depressive symptoms were associated with variability in pain perception and quality of life among patients with nonalcohol-related chronic pancreatitis. Methods. The research design was cross-sectional, and self-report data was collected from 692 patients with nonalcohol-related, intractable pancreatitis. The mean age of the sample was 52.6 (SD = 14.7); 41% of the sample were male. Participants completed the MOS SF12 Quality of Life Measure, the Center for Epidemiological Studies 10-item Depression Scale (CESD), and a numeric rating scale measure of \"pain on average\" from the Brief Pain Inventory. Results. Depressive symptoms were significantly related to participants' reports of increased pain and decreased quality of life. The mean CESD score of the sample was 10.6 (SD = 6.5) and 52% of the sample scored above the clinical cutoff for the presence of significant depressive symptomology. Patients scoring above the clinical cutoff on the depression screening measure rated their pain as significantly higher than those below the cutoff (P < 0.0001) and had significantly lower physical quality of life (P < 0.0001) and lower mental quality of life (P < 0.0001). Conclusion. Although causality cannot be determined based on cross-sectional, correlational data, findings suggest that among patients with nonalcoholic pancreatitis, the presence of depressive symptoms is common and may be a risk factor associated with increased pain and decreased quality of life. Thus, routine screening for depressive symptomology among patients with nonalcoholic pancreatitis may be warranted.", "author" : [ { "dropping-particle" : "", "family" : "Balliet", "given" : "Wendy E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Edwards-Hampton", "given" : "Shenelle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borckardt", "given" : "Jeffery J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morgan", "given" : "Katherine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adams", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Owczarski", "given" : "Stefanie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Madan", "given" : "Alok", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Galloway", "given" : "Sarah K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Serber", "given" : "Eva R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Malcolm", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pain research and treatment", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "978646", "title" : "Depressive Symptoms, Pain, and Quality of Life among Patients with Nonalcohol-Related Chronic Pancreatitis.", "type" : "article-journal", "volume" : "2012" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0256-9574", "PMID" : "26294819", "abstract" : "Chronic pancreatitis (CP) is a progressive and debilitating disease. A potentially important consideration is the relationship between CP, depression and substance use disorders, which seems to be circular and multiplicative. Pain management is a critical component of intervention, and it would seem that in the context of chronic illness this requires a biopsychosocial approach aiming for a tailored intervention that strikes an appropriate therapeutic balance.", "author" : [ { "dropping-particle" : "", "family" : "Jeppe", "given" : "C Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Szabo", "given" : "C P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "M D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2015", "3" ] ] }, "page" : "179-80", "title" : "Chronic pancreatitis, depression and substance use disorders: A not uncommon combination.", "type" : "article-journal", "volume" : "105" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1111/pme.12403", "ISSN" : "1526-4637", "PMID" : "24716629", "abstract" : "OBJECTIVE The objective of this study is to assess clinical variables that may be associated with risk for opioid misuse in individuals with chronic pancreatitis. DESIGN This study utilized a descriptive, quasi-experimental, cross sectional design. SETTING AND PATIENTS Three hundred seven individuals with nonalcoholic chronic pancreatitis engaged in chronic opioid therapy for pain presented to an outpatient specialty clinic at an academic medical center. MEASURES Participants completed the Current Opioid Misuse Measure (COMM), Brief Pain Inventory (BPI), Short Form (SF)-12 Quality of Life Measure, Center for Epidemiological Studies 10-item Depression Scale (CESD), and a single item asking about current alcohol use. Mean scores on the CESD, COMM, BPI, SF-12, and factors associated with opioid misuse measures from regression analyses were the outcome measures. RESULTS Mean scores on the CESD, COMM, BPI pain-on-average item, and the SF-12 physical and psychological quality of life factors (t scores) were 11.2 (standard deviation [SD]\u2009=\u20096.7), 8.5 (SD\u2009=\u20097.3), 4.8 (SD\u2009=\u20092.8), 39.7 (SD\u2009=\u20097.0), and 45 (SD\u2009=\u20099.0), respectively. Descriptive analyses revealed that 55% of participants scored above the clinical cutoff for depression on the CESD, and 39% scored above the cutoff for opioid misuse concerns on the COMM. Regression analyses identified several factors associated with higher opioid misuse measure scores, including increased depressive symptoms from the CESD (\u03b2\u2009=\u20090.38, P\u2009<\u20090.0001), increased pain rating at the time of the office visit (\u03b2\u2009=\u20090.16, P\u2009=\u20090.03), impairment of psychological quality of life (\u03b2\u2009=\u2009-0.27, P\u2009=\u20090.001) and endorsement of alcohol use (\u03b2\u2009=\u20090.16, P\u2009=\u20090.03). These factors accounted for 37% of the variance in current opioid misuse scores. CONCLUSIONS Depression, quality of life, pain intensity and alcohol use may be good candidate variables for prospective studies to determine clinical risk factors for opioid misuse among patients with pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Barth", "given" : "Kelly S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balliet", "given" : "Wendy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pelic", "given" : "Christine M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Madan", "given" : "Alok", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Malcolm", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adams", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morgan", "given" : "Katherine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Owczarski", "given" : "Stefanie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borckardt", "given" : "Jeffrey J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pain medicine (Malden, Mass.)", "id" : "ITEM-3", "issue" : "8", "issued" : { "date-parts" : [ [ "2014", "8", "1" ] ] }, "note" : "NULL", "page" : "1359-64", "title" : "Screening for current opioid misuse and associated risk factors among patients with chronic nonalcoholic pancreatitis pain.", "type" : "article-journal", "volume" : "15" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(54,296,297)", "plainTextFormattedCitation" : "(54,296,297)", "previouslyFormattedCitation" : "(54,296,297)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(54,296,297). Severe chronic pancreatitis pain is also associated with declines in cognitive performance (e.g psychomotor performance, memory, and executive functions)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0023363", "ISSN" : "1932-6203", "PMID" : "21876748", "abstract" : "Chronic pain has been associated with impaired cognitive function. We examined cognitive performance in patients with severe chronic pancreatitis pain. We explored the following factors for their contribution to observed cognitive deficits: pain duration, comorbidity (depression, sleep disturbance), use of opioids, and premorbid alcohol abuse. The cognitive profiles of 16 patients with severe pain due to chronic pancreatitis were determined using an extensive neuropsychological test battery. Data from three cognitive domains (psychomotor performance, memory, executive functions) were compared to data from healthy controls matched for age, gender and education. Multivariate multilevel analysis of the data showed decreased test scores in patients with chronic pancreatitis pain in different cognitive domains. Psychomotor performance and executive functions showed the most prominent decline. Interestingly, pain duration appeared to be the strongest predictor for observed cognitive decline. Depressive symptoms, sleep disturbance, opioid use and history of alcohol abuse provided additional explanations for the observed cognitive decline in some of the tests, but to a lesser extent than pain duration. The negative effect of pain duration on cognitive performance is compatible with the theory of neurodegenerative properties of chronic pain. Therefore, early and effective therapeutic interventions might reduce or prevent decline in cognitive performance, thereby improving outcomes and quality of life in these patients.", "author" : [ { "dropping-particle" : "", "family" : "Jongsma", "given" : "Marijtje L A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Postma", "given" : "Simone A E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Souren", "given" : "Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arns", "given" : "Martijn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gordon", "given" : "Evian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vissers", "given" : "Kris", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "Oliver", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rijn", "given" : "Clementina M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goor", "given" : "Harry", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "editor" : [ { "dropping-particle" : "", "family" : "Pant", "given" : "Harish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2011", "8", "18" ] ] }, "note" : "NULL", "page" : "e23363", "title" : "Neurodegenerative properties of chronic pain: cognitive decline in patients with chronic pancreatitis.", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(298)", "plainTextFormattedCitation" : "(298)", "previouslyFormattedCitation" : "(298)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(298); the co-occurrence of depressive symptoms, sleep disturbance, opioid use, and history of alcohol abuse also predicted cognitive decline. There are a paucity of studies examining the effects of psychological interventions for CP patients. In other chronic pain conditions and gastrointestinal disorders, psychological interventions have shown to be efficacious in reducing chronic pain and pain impactADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/jnu.12213", "ISSN" : "1547-5069", "PMID" : "27149578", "abstract" : "BACKGROUND Patients with chronic pain, depression, and substance use disorder (SUD) are often treated in primary care settings. An estimated 52% of patients have a diagnosis of chronic pain, 5% to 13% have depression, and 19% have SUD. These estimates are likely low when considering the fact that 50% of primary care patients with depression and 65% with SUD are undiagnosed or do not seek help. These three conditions have overlapping neurophysiological processes, which complicate the treatment outcomes of a primary physical illness. Behavioral interventions have been widely utilized as adjunctive treatments, yet little is known about what types of behavioral interventions were effective to treat these comorbidities. This systematic review aimed to identify behavioral interventions targeting chronic pain, depression, and SUD in primary care settings. METHODS The Cumulative Index to Nursing and Allied Health Literature, Medline, PsycInfo, and Google Scholar databases were searched to identify randomized controlled trials, using a behavioral intervention, involving adults with at least two of the three conditions. RESULTS This search yielded 1,862 relevant records, and six articles met final selection criteria. A total of 696 participants were studied. Behavioral interventions varied in content, format, and duration. Mindfulness Oriented Recovery Enhancement (MORE), Acceptance and Commitment Therapy (ACT), Interpersonal Psychotherapy adapted for pain (IPT-P), and Cognitive Behavioral Therapy (CBT) showed promising improvements across all studies, albeit with small to moderate effects. CONCLUSIONS MORE, ACT, and CBT combined with mindfulness and Motivational Interviewing had the most promising results for treating chronic pain, depression, and SUD in various combinations in primary care settings. CLINICAL RELEVANCE The evidence is mounting that behavioral interventions such as mindfulness-based or cognitive-behavioral interventions are effective strategies for managing patients with comorbidities of chronic pain, depression, and SUD in primary care. Integrated delivery of behavioral interventions via group sessions, computers, and smart phones may increase patient access to treatment; save time and cost; reduce stigma, patient distress, family burden, and healthcare fragmentation; and provide a ray of hope to amplify conventional treatments.", "author" : [ { "dropping-particle" : "", "family" : "Barrett", "given" : "Kathleen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chang", "given" : "Yu-Ping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of nursing scholarship : an official publication of Sigma Theta Tau International Honor Society of Nursing", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2016", "7" ] ] }, "note" : "NULL", "page" : "345-53", "title" : "Behavioral Interventions Targeting Chronic Pain, Depression, and Substance Use Disorder in Primary Care.", "type" : "article-journal", "volume" : "48" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.cgh.2012.10.031", "ISSN" : "1542-7714", "PMID" : "23103907", "abstract" : "The functional gastrointestinal disorders (FGIDs) often show inadequate response to usual medical care. Psychological treatments can help improve functional gastrointestinal disorder patient outcomes, and such treatment should be considered for patients who have moderate or severe symptoms after 3-6 months of medical care and those whose symptoms are clearly exacerbated by stress or emotional symptoms. Effective psychological treatments, which are based on multiple randomized controlled trials, include cognitive behavioral therapy and hypnosis for irritable bowel syndrome and pediatric functional abdominal pain, cognitive behavioral therapy for functional chest pain, and biofeedback for dyssynergic constipation in adults. Successful referral by the gastroenterologist for psychological treatment is facilitated by educating the patient about the rationale for such treatment, reassurance about the diagnosis and continuation of medical care, firm doctor-patient therapeutic alliance, and identification of and communication with an appropriate psychological services provider.", "author" : [ { "dropping-particle" : "", "family" : "Palsson", "given" : "Olafur S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Whitehead", "given" : "William E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2013", "3" ] ] }, "note" : "NULL", "page" : "208-16; quiz e22-3", "title" : "Psychological treatments in functional gastrointestinal disorders: a primer for the gastroenterologist.", "type" : "article-journal", "volume" : "11" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(299,300)", "plainTextFormattedCitation" : "(299,300)", "previouslyFormattedCitation" : "(299,300)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(299,300). Behavioral interventions with the most support for chronic pain include cognitive behavioral therapy (CBT), acceptance therapy, mindfulness approaches, and hypnosisADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s11916-016-0562-z", "ISSN" : "1531-3433", "PMID" : "27038968", "abstract" : "There is increasing interest in the use of complimentary and alternative medicine (CAM) for the treatment of chronic pain. This review examines alternative and complimentary therapies, which can be incorporated as part of a biopsychosocial approach in the treatment of chronic pain syndromes. In the present investigation, literature from articles indexed on PubMed was evaluated including topics of alternative therapies, complimentary therapies, pain psychology, biofeedback therapy, physical exercise therapies, acupuncture, natural and herbal supplements, whole-body cryotherapy, and smartphone technologies in the treatment of chronic pain syndromes. This review highlights the key role of psychology in the treatment of chronic pain. Cognitive behavior therapy appears to be the most impactful while biofeedback therapy has also been shown to be effective for chronic pain. Exercise therapy has been shown to be effective in short-, intermediate-, and long-term pain states. When compared to that in sham controls, acupuncture has shown some benefit for neck pain immediately after the procedure and in the short term and improvement has also been demonstrated in the treatment of headaches. The role of smartphones and whole-body cryotherapy are new modalities and further studies are needed. Recent literature suggests that several alternate therapies could play a role in the treatment of chronic pain, supporting the biopsychosocial model in the treatment of pain states.", "author" : [ { "dropping-particle" : "", "family" : "Thomas", "given" : "Donna-Ann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maslin", "given" : "Benjamin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Legler", "given" : "Aron", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Springer", "given" : "Erin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Asgerally", "given" : "Abbas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vadivelu", "given" : "Nalini", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current Pain and Headache Reports", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2016", "5", "2" ] ] }, "note" : "NULL", "page" : "29", "title" : "Role of Alternative Therapies for Chronic Pain Syndromes", "type" : "article-journal", "volume" : "20" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1037/a0035747", "ISSN" : "1935-990X", "PMID" : "24547801", "abstract" : "Over the past three decades, cognitive-behavioral therapy (CBT) has become a first-line psychosocial treatment for individuals with chronic pain. Evidence for efficacy in improving pain and pain-related problems across a wide spectrum of chronic pain syndromes has come from multiple randomized controlled trials. CBT has been tailored to, and found beneficial for, special populations with chronic pain, including children and older adults. Innovations in CBT delivery formats (e.g., Web-based, telephone-delivered) and treatments based on CBT principles that are delivered by health professionals other than psychologists show promise for chronic pain problems. This article reviews (a) the evidence base for CBT as applied to chronic pain, (b) recent innovations in target populations and delivery methods that expand the application of CBT to underserved populations, (c) current limitations and knowledge gaps, and (d) promising directions for improving CBT efficacy and access for people living with chronic pain.", "author" : [ { "dropping-particle" : "", "family" : "Ehde", "given" : "Dawn M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dillworth", "given" : "Tiara M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turner", "given" : "Judith A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American psychologist", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2014" ] ] }, "note" : "NULL", "page" : "153-66", "title" : "Cognitive-behavioral therapy for individuals with chronic pain: efficacy, innovations, and directions for research.", "type" : "article-journal", "volume" : "69" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.pain.2006.12.013", "ISSN" : "1872-6623", "PMID" : "17257755", "abstract" : "An increasing number of studies consider the specific processes by which distressing sensations, thoughts, and emotional experiences exert their influence on the daily functioning of those who suffer with chronic pain. Clinical methods of mindfulness and the processes that underlie them appear to have clear implications in this area, but have not been systematically investigated to this point in time. The purpose of the present study was to examine mindfulness in relation to the pain, emotional, physical, and social functioning of individuals with chronic pain. The present study included 105 consecutive patients attending a clinical assessment for treatment of chronic pain. Each completed a standardized battery of questionnaires, including a measure of mindfulness, the Mindful Attention Awareness Scale [Brown KW, Ryan RM. The benefits of being present: mindfulness and its role in psychological well-being. J Pers Soc Psychol 2003;84:822-48]. Correlation analyses indicated that mindfulness was unrelated to age, gender, education, or chronicity of pain, but was significantly related to multiple measures of patient functioning. In multiple regression analyses, after controlling for patient background variables, pain intensity, and pain-related acceptance, mindfulness accounted for significant variance in measures of depression, pain-related anxiety; physical, psychosocial, and \"other\" disability. In each instance greater mindfulness was associated with better functioning. The combined increments of variance explained from acceptance of pain and mindfulness were at least moderate and, in some cases, appeared potentially meaningful. The behavioral processes of mindfulness and their accessibility to scientific study are considered.", "author" : [ { "dropping-particle" : "", "family" : "McCracken", "given" : "Lance M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gauntlett-Gilbert", "given" : "Jeremy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vowles", "given" : "Kevin E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pain", "id" : "ITEM-3", "issue" : "1-2", "issued" : { "date-parts" : [ [ "2007", "9" ] ] }, "note" : "NULL", "page" : "63-9", "title" : "The role of mindfulness in a contextual cognitive-behavioral analysis of chronic pain-related suffering and disability.", "type" : "article-journal", "volume" : "131" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1080/00207149708416141", "ISSN" : "0020-7144", "PMID" : "9308268", "abstract" : "A cohort of patients with sickle cell disease, consisting of children, adolescents, and adults, who reported experiencing three or more episodes of vaso-occlusive pain the preceding year, were enrolled in a prospective two-period treatment protocol. Following a 4-month conventional treatment baseline phase, a supplemental cognitive-behavioral pain management program that centered on self-hypnosis was implemented over the next 18 months. Frequency of self-hypnosis group straining sessions began at once per week for the first 6 months, became biweekly for the next 6 months, and finally occurred once every third week for the remaining 6 months. Results indicate that the self-hypnosis intervention was associated with a significant reduction in pain days. Both the proportion of \"bad sleep\" nights and the use of pain medications also decreased significantly during the self-hypnosis treatment phase. However, participants continued to report disturbed sleep and to require medications on those days during which they did experience pain. Findings further suggest that the overall reduction in pain frequency was due to the elimination of less severe episodes of pain. Non-specific factors may have contributed to the efficacy of treatment. Nevertheless, the program clearly demonstrates that an adjunctive behavioral treatment for sickle cell pain, involving patient self-management and regular contact with a medical self-hypnosis team, can be beneficial in reducing recurrent, unpredictable episodes of pain in a patient population for whom few safe, cost-effective medical alternatives exist.", "author" : [ { "dropping-particle" : "", "family" : "Dinges", "given" : "D F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Whitehouse", "given" : "W G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Orne", "given" : "E C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bloom", "given" : "P B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carlin", "given" : "M M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bauer", "given" : "N K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gillen", "given" : "K A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shapiro", "given" : "B S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ohene-Frempong", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dampier", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Orne", "given" : "M T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The International journal of clinical and experimental hypnosis", "id" : "ITEM-4", "issue" : "4", "issued" : { "date-parts" : [ [ "1997", "10" ] ] }, "note" : "NULL", "page" : "417-32", "title" : "Self-hypnosis training as an adjunctive treatment in the management of pain associated with sickle cell disease.", "type" : "article-journal", "volume" : "45" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(301\u2013304)", "plainTextFormattedCitation" : "(301\u2013304)", "previouslyFormattedCitation" : "(301\u2013304)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(301–304). There is also growing evidence supporting the neurobiological processes involving the brain-gut axis which increasingly accepted as mediating the effects of psychological interventionsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1053/j.gastro.2012.10.003", "ISSN" : "1528-0012", "PMID" : "23063970", "abstract" : "Psycho-neuro-endocrine-immune modulation through the brain-gut axis likely has a key role in the pathogenesis of inflammatory bowel disease (IBD). The brain-gut axis involves interactions among the neural components, including (1) the autonomic nervous system, (2) the central nervous system, (3) the stress system (hypothalamic-pituitary-adrenal axis), (4) the (gastrointestinal) corticotropin-releasing factor system, and (5) the intestinal response (including the intestinal barrier, the luminal microbiota, and the intestinal immune response). Animal models suggest that the cholinergic anti-inflammatory pathway through an anti-tumor necrosis factor effect of the efferent vagus nerve could be a therapeutic target in IBD through a pharmacologic, nutritional, or neurostimulation approach. In addition, the psychophysiological vulnerability of patients with IBD, secondary to the potential presence of any mood disorders, distress, increased perceived stress, or maladaptive coping strategies, underscores the psychological needs of patients with IBD. Clinicians need to address these issues with patients because there is emerging evidence that stress or other negative psychological attributes may have an effect on the disease course. Future research may include exploration of markers of brain-gut interactions, including serum/salivary cortisol (as a marker of the hypothalamic-pituitary-adrenal axis), heart rate variability (as a marker of the sympathovagal balance), or brain imaging studies. The widespread use and potential impact of complementary and alternative medicine and the positive response to placebo (in clinical trials) is further evidence that exploring other psycho-interventions may be important therapeutic adjuncts to the conventional therapeutic approach in IBD.", "author" : [ { "dropping-particle" : "", "family" : "Bonaz", "given" : "Bruno L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bernstein", "given" : "Charles N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2013", "1" ] ] }, "note" : "NULL", "page" : "36-49", "title" : "Brain-gut interactions in inflammatory bowel disease.", "type" : "article-journal", "volume" : "144" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(305)", "plainTextFormattedCitation" : "(305)", "previouslyFormattedCitation" : "(305)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(305).In one study of 311 CP patients captured during inpatient admissions, a collaborative interdisciplinary treatment program, which included psychological and psychiatric interventions, was associated with reduced healthcare costsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/jhq.12025", "ISSN" : "1945-1474", "PMID" : "24004038", "abstract" : "BACKGROUND Pain is common and multifactorial among patients with chronic pancreatitis. Underrecognized and undertreated psychosocial comorbidity can exacerbate pain experience. Excess inpatient service utilization within this patient population prompted a performance improvement initiative at a large academic medical center. METHODS An interprofessional treatment approach with programmatic medical, surgical, and psychological and psychiatric interventions was rolled-out in January 2007 and length of stay (LOS) was measured on a quarterly basis for a 2-year period. Trends in resource utilization (LOS, estimated opportunity costs) were assessed with a novel modified bootstrapping technique, Simulation Modeling Analysis (SMA). RESULTS From January 1, 2007, through December 31, 2008, SMA revealed a linear downward trend in LOS (\u03c1 = -0.857, p = .0170), and the interprofessional treatment approach was associated with estimated opportunity cost savings of $670,750.27. There were no associated changes in 7-, 14-, and 30-day readmission rates, p > .05. CONCLUSION Interprofessional care that combines behavioral approaches to pain management; behavioral contingency management for opioid medication management; psychological and psychotropic treatments for depression, anxiety, and addiction in addition to standard medical and surgical treatments for pancreatitis appears to be associated with lower healthcare costs. Future research should examine patient reported outcomes of this model.", "author" : [ { "dropping-particle" : "", "family" : "Madan", "given" : "Alok", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borckardt", "given" : "Jeffery J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barth", "given" : "Kelly S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Romagnuolo", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morgan", "given" : "Katherine A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adams", "given" : "David B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal for healthcare quality : official publication of the National Association for Healthcare Quality", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2013", "9" ] ] }, "note" : "NULL", "page" : "41-6", "title" : "Interprofessional collaborative care reduces excess service utilization among individuals with chronic pancreatitis.", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(306)", "plainTextFormattedCitation" : "(306)", "previouslyFormattedCitation" : "(306)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(306). The psychological care included comprehensive psychosocial evaluations about the pain experience, depression, anxiety, post-traumatic stress disorder, substance use/misuse, coping styles, past psychiatric treatment, social support and educational/vocational achievement. Personalized psychological interventions included behavioral approaches to pain management (relaxation, guided imagery), biofeedback, hypnosis, and various psychotherapy modalities (acceptance-based, CBT, brief dynamic, and interpersonal). Psychiatric intervention included psychotropic medications targeting depression and anxiety, optimization of non-opioid pain medications (e.g., gabapentin, SSRI/SNRI, analgesics), screening for and treatment of addiction including buprenorphine/naloxone) and opioid tapers. The study, however did not have a comparison group and did not include standardized treatment protocols, thus it is not possible to attribute cost reduction directly to behavioral interventions.Chronic opioid management is often necessary for residual pain, which increases the risk of addiction and misuseADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.pain.2007.03.028", "ISSN" : "0304-3959", "PMID" : "17482363", "abstract" : "Throughout the long history of opioid drug use by humans, it has been known that opioids are powerful analgesics, but they can cause addiction. It has also been observed, and is now substantiated by multiple reports and studies, that during opioid treatment of severe and short-term pain, addiction arises only rarely. However, when opioids are extended to patients with chronic pain, and therapeutic opioid use is not confined to patients with severe and short-lived pain, compulsive opioid seeking and addiction arising directly from opioid treatment of pain become more visible. Although the epidemiological evidence base currently available is rudimentary, it appears that problematic opioid use arises in some fraction of opioid-treated chronic pain patients, and that problematic behaviors and addiction are problems that need to be addressed. Since the potentially devastating effects of addiction can substantially offset the benefits of opioid pain relief, it seems timely to reexamine addiction mechanisms and their relevance to the practice of long-term opioid treatment for pain. This article reviews the neurobiological and genetic basis of addiction, its terminology and diagnosis, the evidence on addiction rates during opioid treatment of chronic pain and the implications of biological mechanisms in formulating rational opioid treatment regimes.", "author" : [ { "dropping-particle" : "", "family" : "Ballantyne", "given" : "Jane C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "LaForge", "given" : "Steven K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pain", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2007", "6" ] ] }, "note" : "NULL", "page" : "235-255", "title" : "Opioid dependence and addiction during opioid treatment of chronic pain", "type" : "article-journal", "volume" : "129" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1111/j.1526-4637.2007.00370.x", "ISSN" : "1526-2375", "PMID" : "18489635", "abstract" : "DESIGN This is a structured evidence-based review of all available studies on the development of abuse/addiction and aberrant drug-related behaviors (ADRBs) in chronic pain patients (CPPs) with nonmalignant pain on exposure to chronic opioid analgesic therapy (COAT). OBJECTIVES To determine what percentage of CPPs develop abuse/addiction and/or ADRBs on COAT exposure. METHOD Computer and manual literature searches yielded 79 references that addressed this area of study. Twelve of the studies were excluded from detailed review based on exclusion criteria important to this area. Sixty-seven studies were reviewed in detail and sorted according to whether they reported percentages of CPPs developing abuse/addiction or developing ADRBs, or percentages diagnosed with alcohol/illicit drug use as determined by urine toxicology. Study characteristics were abstracted into tabular form, and each report was characterized according to the type of study it represented based on the Agency for Health Care Policy and Research Guidelines. Each study was independently evaluated by two raters according to 12 quality criteria and a quality score calculated. Studies were not utilized in the calculations unless their quality score (utilizing both raters) was greater than 65%. Within each of the above study groupings, the total number of CPPs exposed to opioids on COAT treatment was calculated. Similarly, the total number of CPPs in each grouping demonstrating abuse/addiction, ADRBs, or alcohol/illicit drug use was also calculated. Finally, a percentage for each of these behaviors was calculated in each grouping, utilizing the total number of CPPs exposed to opioids in each grouping. RESULTS All 67 reports had quality scores greater than 65%. For the abuse/addiction grouping there were 24 studies with 2,507 CPPs exposed for a calculated abuse/addiction rate of 3.27%. Within this grouping for those studies that had preselected CPPs for COAT exposure for no previous or current history of abuse/addiction, the percentage of abuse/addiction was calculated at 0.19%. For the ADRB grouping, there were 17 studies with 2,466 CPPs exposed and a calculated ADRB rate of 11.5%. Within this grouping for preselected CPPs (as above), the percentage of ADRBs was calculated at 0.59%. In the urine toxicology grouping, there were five studies (15,442 CPPs exposed). Here, 20.4% of the CPPs had no prescribed opioid in urine and/or a nonprescribed opioid in urine. For five studies (1,965 CPPs exposed\u2026", "author" : [ { "dropping-particle" : "", "family" : "Fishbain", "given" : "David A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cole", "given" : "Brandly", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lewis", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rosomoff", "given" : "Hubert L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rosomoff", "given" : "R. Steele", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pain Medicine", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2008", "5", "1" ] ] }, "note" : "NULL", "page" : "444-459", "title" : "What Percentage of Chronic Nonmalignant Pain Patients Exposed to Chronic Opioid Analgesic Therapy Develop Abuse/Addiction and/or Aberrant Drug-Related Behaviors? A Structured Evidence-Based Review", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(307,308)", "plainTextFormattedCitation" : "(307,308)", "previouslyFormattedCitation" : "(307,308)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(307,308). Identification of risk factors for opioid addiction is criticalADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.ejpain.2006.08.004", "ISSN" : "1090-3801", "PMID" : "17070082", "abstract" : "Opioids have proven very useful for treatment of acute pain and cancer pain, and in the developed countries opioids are increasingly used for treatment of chronic non-malignant pain patients as well. This literature review aims at giving an overview of definitions, mechanisms, diagnostic criteria, incidence and prevalence of addiction in opioid treated pain patients, screening tools for assessing opioid addiction in chronic pain patients and recommendations regarding addiction problems in national and international guidelines for opioid treatment in cancer patients and chronic non-malignant pain patients. The review indicates that the prevalence of addiction varied from 0% up to 50% in chronic non-malignant pain patients, and from 0% to 7.7% in cancer patients depending of the subpopulation studied and the criteria used. The risk of addiction has to be considered when initiating long-term opioid treatment as addiction may result in poor pain control. Several screening tools were identified, but only a few were thoroughly validated with respect to validity and reliability. Most of the identified guidelines mention addiction as a potential problem. The guidelines in cancer pain management are concerned with the fact that pain may be under treated because of fear of addiction, and the guidelines in management of non-malignant pain patients include warnings of addiction. According to the literature, it seems appropriate and necessary to be aware of the problems associated with addiction during long-term opioid treatment, and specialised treatment facilities for pain management or addiction medicine should be consulted in these cases.", "author" : [ { "dropping-particle" : "", "family" : "H\u00f8jsted", "given" : "Jette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sj\u00f8gren", "given" : "Per", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European journal of pain (London, England)", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2007", "7" ] ] }, "note" : "NULL", "page" : "490-518", "title" : "Addiction to opioids in chronic pain patients: a literature review.", "type" : "article-journal", "volume" : "11" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(309)", "plainTextFormattedCitation" : "(309)", "previouslyFormattedCitation" : "(309)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(309). In one study, clinical risks for opioid misuse in patients with chronic nonalcoholic pancreatitis included depression, poor quality of life and alcohol useADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/pme.12403", "ISSN" : "1526-4637", "PMID" : "24716629", "abstract" : "OBJECTIVE The objective of this study is to assess clinical variables that may be associated with risk for opioid misuse in individuals with chronic pancreatitis. DESIGN This study utilized a descriptive, quasi-experimental, cross sectional design. SETTING AND PATIENTS Three hundred seven individuals with nonalcoholic chronic pancreatitis engaged in chronic opioid therapy for pain presented to an outpatient specialty clinic at an academic medical center. MEASURES Participants completed the Current Opioid Misuse Measure (COMM), Brief Pain Inventory (BPI), Short Form (SF)-12 Quality of Life Measure, Center for Epidemiological Studies 10-item Depression Scale (CESD), and a single item asking about current alcohol use. Mean scores on the CESD, COMM, BPI, SF-12, and factors associated with opioid misuse measures from regression analyses were the outcome measures. RESULTS Mean scores on the CESD, COMM, BPI pain-on-average item, and the SF-12 physical and psychological quality of life factors (t scores) were 11.2 (standard deviation [SD]\u2009=\u20096.7), 8.5 (SD\u2009=\u20097.3), 4.8 (SD\u2009=\u20092.8), 39.7 (SD\u2009=\u20097.0), and 45 (SD\u2009=\u20099.0), respectively. Descriptive analyses revealed that 55% of participants scored above the clinical cutoff for depression on the CESD, and 39% scored above the cutoff for opioid misuse concerns on the COMM. Regression analyses identified several factors associated with higher opioid misuse measure scores, including increased depressive symptoms from the CESD (\u03b2\u2009=\u20090.38, P\u2009<\u20090.0001), increased pain rating at the time of the office visit (\u03b2\u2009=\u20090.16, P\u2009=\u20090.03), impairment of psychological quality of life (\u03b2\u2009=\u2009-0.27, P\u2009=\u20090.001) and endorsement of alcohol use (\u03b2\u2009=\u20090.16, P\u2009=\u20090.03). These factors accounted for 37% of the variance in current opioid misuse scores. CONCLUSIONS Depression, quality of life, pain intensity and alcohol use may be good candidate variables for prospective studies to determine clinical risk factors for opioid misuse among patients with pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Barth", "given" : "Kelly S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balliet", "given" : "Wendy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pelic", "given" : "Christine M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Madan", "given" : "Alok", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Malcolm", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adams", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morgan", "given" : "Katherine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Owczarski", "given" : "Stefanie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borckardt", "given" : "Jeffrey J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pain medicine (Malden, Mass.)", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2014", "8", "1" ] ] }, "note" : "NULL", "page" : "1359-64", "title" : "Screening for current opioid misuse and associated risk factors among patients with chronic nonalcoholic pancreatitis pain.", "type" : "article-journal", "volume" : "15" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(297)", "plainTextFormattedCitation" : "(297)", "previouslyFormattedCitation" : "(297)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(297). Behavioral intervention and psychosocial resources are critical to prevent or treat opioid misuse and dependence in patients with CPADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0163-8343", "PMID" : "10228897", "author" : [ { "dropping-particle" : "", "family" : "Meana", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pruitt", "given" : "S D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dresselhaus", "given" : "T R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "General hospital psychiatry", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "0" ] ] }, "note" : "NULL", "page" : "137-40", "title" : "Opioid therapy for chronic pancreatitis: controlling aberrant use through behavioral management.", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(310)", "plainTextFormattedCitation" : "(310)", "previouslyFormattedCitation" : "(310)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(310). A strong empathic doctor-patient relationship is also key. Successful opioid detoxification strategies have also been demonstrated, though recidivism was high at 6 monthsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ajg.2012.142", "ISSN" : "1572-0241", "PMID" : "22710577", "abstract" : "UNLABELLED OBFECTIVES: Narcotic bowel syndrome (NBS) is characterized by a paradoxical increase in abdominal pain associated with continued or escalating dosages of narcotics. This study evaluated the clinical and psychosocial features of patients with NBS and the response to detoxification treatment. METHODS For 2 years, 39 patients seen by the GI consult service at the University of North Carolina at Chapel Hill (UNC) with presumed NBS were placed on a detoxification program. Clinical, psychosocial, health status, and outcome data were obtained before and after detoxification. Our aims were to: (i) clinically characterize patients with presumed NBS, (ii) assess the clinical response and adverse effects to detoxification, (iii) identify clinical and psychosocial predictors of treatment response, and (iv) determine the clinical outcome at 3 months after detoxification and the time frame for patients who revert back to narcotics. RESULTS Of the 39 patients detoxified, 89.7% met predefined criteria. Patients were mostly well educated (14.5 \u00b1 2.3 years of school), female (92.3%), and with a variety of diagnoses (21% irritable bowel syndrome IBS/functional, 37% inflammatory bowel disease and other structural, 29% fibromyalgia and other functional somatic, or orthopedic, and 13% postoperative or other). They reported high health-care use (15.3 \u00b1 10.1 MD visits/6 months; 6.5 \u00b1 6.1 hospitalizations/2 years, 6.4 \u00b1 2.0 surgeries/lifetime), and 82.1% were jobless. Despite high dosages of narcotics (total intravenous (IV) morphine equivalent 75.3 \u00b1 78.0 \u2009mg/day), pain scores were rated severe (52.9 \u00b1 28.8 visual analog scale (VAS); 257.1 \u00b1 139.6 functional bowel disorder severity index (FBDSI); 17.2 \u00b1 10.2 (McGill Pain and greater than labor or postoperative pain). Multiple symptoms were reported (n = 17.8 \u00b1 9.2) and rated as moderate to severe. Psychosocial scores showed high catastrophizing (19.9 \u00b1 8.6); poor daily function (Short Form-36 (SF-36) physical 28.3 \u00b1 7.7, mental 34.3 \u00b1 11.0; worse than tetraplegia); 28.2% were clinically depressed and 33.3% anxious (Hospital Anxiety and Depression Scale (HADS)). Detoxification was successfully completed by 89.7%; after detoxification, abdominal pain was reduced by 35% (P < 0.03) and nonabdominal pain by 42% (P < 0.01) on VAS, and catastrophizing significantly improved (P < 0.01). Responder status was met in 56.4% with 48.7% achieving a \u2265 30% reduction in pain. By 3 months after detoxification, 45.8% had returned to u\u2026", "author" : [ { "dropping-particle" : "", "family" : "Drossman", "given" : "Douglas A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Carolyn B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Edwards", "given" : "Hollie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wrennall", "given" : "Christina Ed", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weinland", "given" : "Stephan R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aderoju", "given" : "Ademola O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kulkarni-Kelapure", "given" : "Renuka R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Yuming J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dalton", "given" : "Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bouma", "given" : "Megan H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zimmerman", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rooker", "given" : "Ceciel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leserman", "given" : "Jane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bangdiwala", "given" : "Shrikant I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American journal of gastroenterology", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2012", "9", "19" ] ] }, "note" : "NULL", "page" : "1426-40", "title" : "Diagnosis, characterization, and 3-month outcome after detoxification of 39 patients with narcotic bowel syndrome.", "type" : "article-journal", "volume" : "107" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(311)", "plainTextFormattedCitation" : "(311)", "previouslyFormattedCitation" : "(311)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(311). Children with CP painChildren with CP represent an important subgroup who experiences frequent pancreatitis-related abdominal painADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1001/jamapediatrics.2015.4955", "ISSN" : "2168-6211", "PMID" : "27064572", "abstract" : "IMPORTANCE Pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) are poorly understood. OBJECTIVE To characterize and identify risk factors associated with ARP and CP in childhood. DESIGN, SETTING, AND PARTICIPANTS A multinational cross-sectional study of children with ARP or CP at the time of enrollment to the INSPPIRE (International Study Group of Pediatric Pancreatitis: In Search for a Cure) study at participant institutions of the INSPPIRE Consortium. From August 22, 2012, to February 8, 2015, 155 children with ARP and 146 with CP (aged \u226419 years) were enrolled. Their demographic and clinical information was entered into the REDCap (Research Electronic Data Capture) database at the 15 centers. Differences were analyzed using 2-sample t test or Wilcoxon rank sum test for continuous variables and Pearson \u03c72 test or Fisher exact test for categorical variables. Disease burden variables (pain variables, hospital/emergency department visits, missed school days) were compared using Wilcoxon rank sum test. MAIN OUTCOMES AND MEASURES Demographic characteristics, risk factors, abdominal pain, and disease burden. RESULTS A total of 301 children were enrolled (mean [SD] age, 11.9 [4.5] years; 172 [57%] female); 155 had ARP and 146 had CP. The majority of children with CP (123 of 146 [84%]) reported prior recurrent episodes of acute pancreatitis. Sex distribution was similar between the groups (57% female in both). Hispanic children were less likely to have CP than ARP (17% vs 28%, respectively; odds ratio [OR]\u2009=\u20090.51; 95% CI, 0.29-0.92; P\u2009=\u2009.02). At least 1 gene mutation in pancreatitis-related genes was found in 48% of patients with ARP vs 73% of patients with CP (P\u2009<\u2009.001). Children with PRSS1 or SPINK1 mutations were more likely to present with CP compared with ARP (PRSS1: OR\u2009=\u20094.20; 95% CI, 2.14-8.22; P\u2009<\u2009.001; and SPINK1: OR\u2009=\u20092.30; 95% CI, 1.03-5.13; P\u2009=\u2009.04). Obstructive risk factors did not differ between children with ARP or CP (33% in both the ARP and CP groups), but toxic/metabolic risk factors were more common in children with ARP (21% overall; 26% in the ARP group and 15% in the CP group; OR\u2009=\u20090.55; 95% CI, 0.31-0.99; P\u2009=\u2009.046). Pancreatitis-related abdominal pain was a major symptom in 81% of children with ARP or CP within the last year. The disease burden was greater in the CP group compared with the ARP group (more emergency department visits, hospitalizations, and medical, endoscopic, and surgical interventions). CONCLUSION\u2026", "author" : [ { "dropping-particle" : "", "family" : "Kumar", "given" : "Soma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ooi", "given" : "Chee Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Werlin", "given" : "Steven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abu-El-Haija", "given" : "Maisam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barth", "given" : "Bradley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bellin", "given" : "Melena D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Durie", "given" : "Peter R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fishman", "given" : "Douglas S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freedman", "given" : "Steven D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gariepy", "given" : "Cheryl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giefer", "given" : "Matthew J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gonska", "given" : "Tanja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heyman", "given" : "Melvin B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Himes", "given" : "Ryan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Husain", "given" : "Sohail Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lin", "given" : "Tom K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lowe", "given" : "Mark E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morinville", "given" : "Veronique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palermo", "given" : "Joseph J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pohl", "given" : "John F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwarzenberg", "given" : "Sarah Jane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Troendle", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilschanski", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zimmerman", "given" : "M Bridget", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uc", "given" : "Aliye", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "JAMA pediatrics", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2016", "6", "1" ] ] }, "note" : "NULL", "page" : "562-9", "title" : "Risk Factors Associated With Pediatric Acute Recurrent and Chronic Pancreatitis: Lessons From INSPPIRE.", "type" : "article-journal", "volume" : "170" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(312)", "plainTextFormattedCitation" : "(312)", "previouslyFormattedCitation" : "(312)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(312), reduced quality of life and significant problems with fatigueADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/MPG.0b013e3182407c4f", "ISSN" : "1536-4801", "PMID" : "22094900", "abstract" : "OBJECTIVES There are limited data on health-related quality of life (HRQOL) in pediatric patients with long-standing pancreatitis (including acute relapsing and chronic pancreatitis) using age-appropriate measurement instruments. METHODS We evaluated HRQOL in children with long-standing pancreatitis using the PedsQL 4.0 Generic Core Scales by patient self-report as well as parent proxy report. Additionally, patient self-reports and parent proxy reports were completed for the PedsQL Multidimensional Fatigue Scale. RESULTS Across all of the dimensions, significantly impaired HRQOL and higher fatigue were noted for both pediatric patient self-report and parent proxy report in comparison with the matched healthy children samples. Higher fatigue was associated with lower HRQOL. There was moderate to good agreement between patient self-reports and parent proxy reports. CONCLUSIONS Given the impaired HRQOL and fatigue documented in the present study, future studies are needed to determine whether specific factors can modify HRQOL and fatigue in this patient population.", "author" : [ { "dropping-particle" : "", "family" : "Pohl", "given" : "John F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Limbers", "given" : "Christine A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kay", "given" : "Marie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harman", "given" : "Annette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rollins", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Varni", "given" : "James W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of pediatric gastroenterology and nutrition", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2012", "5" ] ] }, "note" : "NULL", "page" : "657-63", "title" : "Health-related quality of life in pediatric patients with long-standing pancreatitis.", "type" : "article-journal", "volume" : "54" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(313)", "plainTextFormattedCitation" : "(313)", "previouslyFormattedCitation" : "(313)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(313). Similar to the impact of chronic pain in other pediatric chronic conditions, children with chronic CP also have severe disease burden, high health care utilization and costsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/MPG.0000000000001057", "ISSN" : "1536-4801", "PMID" : "26704866", "abstract" : "OBJECTIVE To estimate selected direct medical care costs of children with chronic pancreatitis (CP) and acute recurrent pancreatitis (ARP). METHODS We performed a cross-sectional study of data from International Study Group of Pediatric Pancreatitis: In Search for a Cure (INSPPIRE), a multinational registry of children with ARP or CP. We determined health care utilization and estimated costs of hospitalizations, surgical and endoscopic procedures, and medications in our study population. Health care utilization data were obtained from all subjects enrolled in the study, and costs were calculated using national United States costs. RESULTS We included 224 subjects (median age 12.7 years), 42% of whom had CP. Mean number of hospitalizations, including for surgery and endoscopic retrograde cholangiopancreatography, was 2.3 per person per year, costing an estimated average $38,755 per person per year. Including outpatient medications, estimated total mean cost was $40,589 per person per year. Subjects using surgical procedures or endoscopic retrograde cholangiopancreatography incurred mean annual costs of $42,951 per person and $12,035 per person, respectively. Estimated annual costs of pancreatic enzyme replacement therapy, diabetic medications, and pain medications were $4114, $1761, and $614 per person, respectively. In an exploratory analysis, patients with the following characteristics appear to accrue higher costs than those without them: more frequent ARP attacks per year, reported constant or episodic pain, family history of pancreatic cancer, and use of pain medication. CONCLUSIONS ARP and CP are uncommon childhood conditions. The severe burden of disease associated with these conditions and their chronicity results in high health care utilization and costs. Interventions that reduce the need for hospitalization could lower costs for these children and their families.", "author" : [ { "dropping-particle" : "", "family" : "Ting", "given" : "Jie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilson", "given" : "Leslie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwarzenberg", "given" : "Sarah Jane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Himes", "given" : "Ryan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barth", "given" : "Bradley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bellin", "given" : "Melena D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Durie", "given" : "Peter R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fishman", "given" : "Douglas S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freedman", "given" : "Steven D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gariepy", "given" : "Cheryl E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giefer", "given" : "Matthew J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gonska", "given" : "Tanja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Husain", "given" : "Sohail Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "Soma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morinville", "given" : "Veronique D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lowe", "given" : "Mark E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ooi", "given" : "Chee Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pohl", "given" : "John F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Troendle", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Usatin", "given" : "Danielle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Werlin", "given" : "Steven L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilschanski", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heyman", "given" : "Melvin B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uc", "given" : "Aliye", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of pediatric gastroenterology and nutrition", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2016", "3" ] ] }, "note" : "NULL", "page" : "443-9", "title" : "Direct Costs of Acute Recurrent and Chronic Pancreatitis in Children in the INSPPIRE Registry.", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(314)", "plainTextFormattedCitation" : "(314)", "previouslyFormattedCitation" : "(314)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(314). Moreover, children also experience the functional impact of CP on their ability to attend school. In one study, 70% of children with CP indicated one or more missed days of school in the past month due to chronic pancreatitis and one-third of children had missed 3 or more days of school in the most recent monthADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jpeds.2014.11.019", "ISSN" : "1097-6833", "PMID" : "25556020", "abstract" : "OBJECTIVE To determine the clinical presentation, diagnostic variables, risk factors, and disease burden in children with chronic pancreatitis. STUDY DESIGN We performed a cross-sectional study of data from the International Study Group of Pediatric Pancreatitis: In Search for a Cure, a registry of children with acute recurrent pancreatitis and chronic pancreatitis. Between-group differences were compared using Wilcoxon rank-sum test. RESULTS Among 170 subjects in the registry, 76 (45%) had chronic pancreatitis; 57% were female, 80% were white; median age at diagnosis was 9.9 years. Pancreatitis-predisposing genetic mutations were identified in 51 (67%) and obstructive risk factors in 25 (33%). Toxic/metabolic and autoimmune factors were uncommon. Imaging demonstrated ductal abnormalities and pancreatic atrophy more commonly than calcifications. Fifty-nine (77%) reported abdominal pain within the past year; pain was reported as constant and receiving narcotics in 28%. Children with chronic pancreatitis reported a median of 3 emergency department visits and 2 hospitalizations in the last year. Forty-seven subjects (70%) missed 1 day of school in the past month as the result of chronic pancreatitis; 26 (34%) missed 3 or more days. Children reporting constant pain were more likely to miss school (P = .002), visit the emergency department (P = .01), and experience hospitalizations (P = .03) compared with children with episodic pain. Thirty-three children (43%) underwent therapeutic endoscopic retrograde pancreatography; one or more pancreatic surgeries were performed in 30 (39%). CONCLUSIONS Chronic pancreatitis occurs at a young age with distinct clinical features. Genetic and obstructive risk factors are common, and disease burden is substantial.", "author" : [ { "dropping-particle" : "", "family" : "Schwarzenberg", "given" : "Sarah Jane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bellin", "given" : "Melena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Husain", "given" : "Sohail Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ahuja", "given" : "Monika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barth", "given" : "Bradley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davis", "given" : "Heather", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Durie", "given" : "Peter R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fishman", "given" : "Douglas S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freedman", "given" : "Steven D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gariepy", "given" : "Cheryl E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giefer", "given" : "Matthew J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gonska", "given" : "Tanja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heyman", "given" : "Melvin B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Himes", "given" : "Ryan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "Soma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morinville", "given" : "Veronique D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lowe", "given" : "Mark E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nuehring", "given" : "Neil E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ooi", "given" : "Chee Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pohl", "given" : "John F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Troendle", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Werlin", "given" : "Steven L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilschanski", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yen", "given" : "Elizabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uc", "given" : "Aliye", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of pediatrics", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2015", "4" ] ] }, "note" : "NULL", "page" : "890-6.e1", "title" : "Pediatric chronic pancreatitis is associated with genetic risk factors and substantial disease burden.", "type" : "article-journal", "volume" : "166" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(315)", "plainTextFormattedCitation" : "(315)", "previouslyFormattedCitation" : "(315)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(315). Additional research is critically needed to understand the epidemiology of chronic pancreatitis pain in children, risk factors for chronic pain and poor quality of life, and treatment approaches that may improve pain and quality of life for children. Longitudinal research will be particularly informative for understanding trajectories of pain into adulthood. Because CP pain and its impact have only recently been recognized in the pediatric population, there are no studies of neurolytical or psychological treatments conducted to date. Psychological treatments for other forms of pediatric chronic pain, including abdominal pain, are well studied and have promising effects. Treatments have included predominantly cognitive-behavioral interventions such as pain education, relaxation training, pain-specific cognitive therapy, and behavioral activation. Social learning theories have also guided treatment in children where intervention strategies focus on modifying parent behavior that may inadvertently reinforce maladaptive coping (such as teaching parents to reward activity participation like attending school). In the most recent systematic review of the efficacy of RCTs of psychological therapies for a range of pediatric chronic pain conditions including abdominal painADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/jpepsy/jsu008", "ISSN" : "0146-8693", "PMID" : "24602890", "abstract" : "OBJECTIVES This systematic review and meta-analysis examined the effects of psychological therapies for management of chronic pain in children.\u2003 METHODS Randomized controlled trials of psychological interventions treating children (<18 years) with chronic pain conditions including headache, abdominal, musculoskeletal, or neuropathic pain were searched for. Pain symptoms, disability, depression, anxiety, and sleep outcomes were extracted. Risk of bias was assessed and quality of the evidence was rated using GRADE.\u2003 RESULTS 35 included studies revealed that across all chronic pain conditions, psychological interventions reduced pain symptoms and disability posttreatment. Individual pain conditions were analyzed separately. Sleep outcomes were not reported in any trials. Optimal dose of treatment was explored. For headache pain, higher treatment dose led to greater reductions in pain. No effect of dosage was found for other chronic pain conditions.\u2003 CONCLUSIONS Evidence for psychological therapies treating chronic pain is promising. Recommendations for clinical practice and research are presented.", "author" : [ { "dropping-particle" : "", "family" : "Fisher", "given" : "E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heathcote", "given" : "L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palermo", "given" : "T. M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "C Williams", "given" : "A. C.", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lau", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eccleston", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Pediatric Psychology", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2014", "9", "1" ] ] }, "note" : "NULL", "page" : "763-782", "title" : "Systematic Review and Meta-Analysis of Psychological Therapies for Children With Chronic Pain", "type" : "article-journal", "volume" : "39" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(316)", "plainTextFormattedCitation" : "(316)", "previouslyFormattedCitation" : "(316)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(316), moderate effects on pain and small effects on reducing disability were found at post-treatment. Unfortunately, even when effective psychological treatments are developed major barriers exist for families to access specialized pediatric pain services due to the geographical distance that separates most families from pediatric pain specialists. Very limited clinical resources are available to treat pediatric chronic pain and this shortage of treatment centersADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/BF03016632", "ISSN" : "0832-610X", "PMID" : "18056207", "abstract" : "PURPOSE The objective of this study was to examine the services currently offered by multidisciplinary pain treatment facilities (MPTFs) dedicated for pediatric chronic pain management across Canada. METHODS A MPTF was defined as a clinic that advertised specialized multidisciplinary services for the diagnosis and management of chronic pain and had a minimum of three different health care disciplines (including at least one medical speciality) available and integrated within the facility. The search method was previously described in an accompanying article. Designated investigators were responsible for confirming and supplementing MPTFs from the preliminary list in their respective provinces. Administrative leads at each eligible MPTF were asked to complete a detailed questionnaire on their infrastructure, clinical, research, teaching and administrative activities. Only MPTFs dedicated to pediatric populations were included. RESULTS Only five centres surveyed had dedicated pediatric MPTFs, all located in major cities in five different provinces. While the median wait time was four weeks, it could be as long as nine months in one MPTF. Headache and neuropathic pain were the most commonly treated pain syndromes. All MPTFs included physicians, nurses and psychologists, and used a rehabilitation model that incorporated a wide variety of pharmacological, psychological and physical therapies. All centres provided training for medical and other healthcare professionals, and three of the five centres conducted research. Government funding was the major source of funding for patient services and overhead costs. CONCLUSIONS There are very few pediatric MPTFs in Canada. These facilities exist in five of ten provinces, each within large urban centres. Limited accessibility leads to variable and prolonged wait times for pediatric patients suffering from chronic pain.", "author" : [ { "dropping-particle" : "", "family" : "Peng", "given" : "Philip", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stinson", "given" : "Jennifer N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Choiniere", "given" : "Manon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dion", "given" : "Dominique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Intrater", "given" : "Howard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lefort", "given" : "Sandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lynch", "given" : "Mary", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ong", "given" : "May", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rashiq", "given" : "Saifee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tkachuk", "given" : "Gregg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Veillette", "given" : "Yves", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "STOPPAIN Investigators Group", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Canadian journal of anaesthesia = Journal canadien d'anesthesie", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2007", "12" ] ] }, "note" : "NULL", "page" : "985-91", "title" : "Dedicated multidisciplinary pain management centres for children in Canada: the current status.", "type" : "article-journal", "volume" : "54" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(317)", "plainTextFormattedCitation" : "(317)", "previouslyFormattedCitation" : "(317)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(317) has been identified as a major barrier contributing to an unmet clinical need. Availability of information and communication technology has expanded opportunities for reaching families remotely. An emerging evidence base now exists for internet-delivered psychological interventions for chronic pain in both adult and pediatric populationsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.pain.2011.02.012", "ISSN" : "1872-6623", "PMID" : "21565446", "abstract" : "Given the increasing penetration and health care related use of the Internet, we examined the evidence on the impact of Internet-based interventions on pain. A search of Medline, CINAHL, PsycINFO, and the Cochrane Library was conducted for literature published from 1990 to 2010 describing randomized controlled trials that assessed the effects of Internet-based interventions on patients with pain of any kind. Of 6724 citations, 17 articles were included. The studies evaluated the effects of interventions that provided cognitive and behavioral therapy, moderated peer support programs, or clinical visit preparation or follow-up support on 2503 people in pain. Six studies (35.3%) received scores associated with high quality. Most cognitive and behavioral therapy studies showed an improvement in pain (n=7, 77.8%), activity limitation (n=4, 57.1%) and costs associated with treatment (n=3, 100%), whereas effects on depression (n=2, 28.6%) and anxiety (n=2, 50%) were less consistent. There was limited (n=2 from same research group) but promising evidence that Internet-based peer support programs can lead to improvements in pain intensity, activity limitation, health distress and self-efficacy; limited (n=4 from same research group) but promising evidence that social networking programs can reduce pain in children and adolescents; and insufficient evidence on Internet-based clinical support interventions. Internet-based interventions seem promising for people in pain, but it is still unknown what types of patients benefit most. More well-designed studies with diverse patient groups, active control conditions, and a better description of withdrawals are needed to strengthen the evidence concerning the impact of Internet-based interventions on people in pain.", "author" : [ { "dropping-particle" : "", "family" : "Bender", "given" : "Jacqueline L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Radhakrishnan", "given" : "Arun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Diorio", "given" : "Caroline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Englesakis", "given" : "Marina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jadad", "given" : "Alejandro R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pain", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2011", "8" ] ] }, "note" : "NULL", "page" : "1740-50", "title" : "Can pain be managed through the Internet? A systematic review of randomized controlled trials.", "type" : "article-journal", "volume" : "152" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/14651858.CD011118.pub2", "ISSN" : "1469-493X", "PMID" : "25803793", "abstract" : "BACKGROUND Chronic pain is common during childhood and adolescence and is associated with negative outcomes such as increased severity of pain, reduced function (e.g. missing school), and low mood (e.g. high levels of depression and anxiety). Psychological therapies, traditionally delivered face-to-face with a therapist, are efficacious at reducing pain intensity and disability. However, new and innovative technology is being used to deliver these psychological therapies remotely, meaning barriers to access to treatment such as distance and cost can be removed or reduced. Therapies delivered with technological devices, such as the Internet, computer-based programmes, smartphone applications, or via the telephone, can be used to deliver treatment to children and adolescents with chronic pain. OBJECTIVES To determine the efficacy of psychological therapies delivered remotely compared to waiting-list, treatment-as-usual, or active control treatments, for the management of chronic pain in children and adolescents. SEARCH METHODS We searched four databases (CENTRAL, MEDLINE, EMBASE, and PsycINFO) from inception to June 2014 for randomised controlled trials of remotely delivered psychological interventions for children and adolescents (0 to 18 years of age) with chronic pain. We searched for chronic pain conditions including, but not exclusive to, headache, recurrent abdominal pain, musculoskeletal pain, and neuropathic pain. We also searched online trial registries for potential trials. A citation and reference search for all included studies was conducted. SELECTION CRITERIA All included studies were randomised controlled trials that investigated the efficacy of a psychological therapy delivered remotely via the Internet, smartphone device, computer-based programme, audiotapes, or over the phone in comparison to an active, treatment-as-usual, or waiting-list control. We considered blended treatments, which used a combination of technology and face-to-face interaction. We excluded interventions solely delivered face-to-face between therapist and patient from this review. Children and adolescents (0 to 18 years of age) with a primary chronic pain condition were the target of the interventions. Each comparator arm, at each extraction point had to include 10 or more participants. DATA COLLECTION AND ANALYSIS For the analyses, we combined all psychological therapies. We split pain conditions into headache and mixed (non-headache) pain and analysed them separatel\u2026", "author" : [ { "dropping-particle" : "", "family" : "Fisher", "given" : "Emma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Law", "given" : "Emily", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palermo", "given" : "Tonya M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eccleston", "given" : "Christopher", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Cochrane database of systematic reviews", "editor" : [ { "dropping-particle" : "", "family" : "Fisher", "given" : "Emma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2015", "3", "23" ] ] }, "note" : "NULL", "page" : "CD011118", "publisher" : "John Wiley & Sons, Ltd", "publisher-place" : "Chichester, UK", "title" : "Psychological therapies (remotely delivered) for the management of chronic and recurrent pain in children and adolescents.", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1097/AJP.0000000000000185", "ISSN" : "1536-5409", "PMID" : "25411862", "abstract" : "OBJECTIVES The use of technology to provide chronic pain self-management interventions has increased in the recent years. Individual studies have primarily focused on a single technology-assisted modality and direct comparisons of different technology-assisted modalities are rare. Thus, little is known about the relative strengths and weaknesses of each technology-assisted modality. MATERIALS AND METHODS This article is a systematic review of technology-assisted self-management interventions for chronic nonheadache, noncancer pain in adults. We examined 3 treatment modalities: telephone, interactive voice response, and Internet. Electronic searches of OVID MEDLINE, OVID PsychINFO, and the Cochrane Database of Systematic Reviews were conducted. Forty-four articles including 9890 participants were reviewed. RESULTS Across modalities, the existing evidence suggests that technology-assisted psychological interventions are efficacious for improving self-management of chronic pain in adults. All modalities have been shown to provide benefit and no clearly superior modality has emerged. The primary gaps in the literature are lack of in-person comparison groups, lack of direct comparison among technology-assisted modalities, and heterogeneity of methods and interventions that limit comparability across studies and modalities. DISCUSSION Future trials should focus on direct comparisons of technology-assisted interventions with in-person treatment and head to head comparisons of different technology-assisted modalities. Additional areas of focus include quantifying the cost of technology-assisted interventions, examining the effect of treatment \"dose\" on outcomes, and establishing guidelines for developing treatments for the technology-assisted environment.", "author" : [ { "dropping-particle" : "", "family" : "Heapy", "given" : "Alicia A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Higgins", "given" : "Diana M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cervone", "given" : "Dana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wandner", "given" : "Laura", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fenton", "given" : "Brenda T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kerns", "given" : "Robert D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Clinical journal of pain", "id" : "ITEM-3", "issue" : "6", "issued" : { "date-parts" : [ [ "2015", "6" ] ] }, "note" : "NULL", "page" : "470-92", "title" : "A Systematic Review of Technology-assisted Self-Management Interventions for Chronic Pain: Looking Across Treatment Modalities.", "type" : "article-journal", "volume" : "31" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(318\u2013320)", "plainTextFormattedCitation" : "(318\u2013320)", "previouslyFormattedCitation" : "(318\u2013320)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(318–320), with patients showing improvements in pain and disability. A major priority in treatment of chronic pancreatitis pain is to develop and evaluate low-cost psychological treatments to reduce pain and improve quality of life both for children and adults. Güralp O Ceyhan, Harry van Goor and Stefan A W BouwenseQ10. What is the optimal surgical approach to relief pain in chronic pancreatitis Depending on the morphological changes of the pancreas and pain processing status a (partially) resection, decompression of the pancreatic duct or combined intervention can be performed to reduce pain. Long-term effects are variable, however success rates up to 80% have been reported. The emerging role of total pancreatectomy as initial surgical treatment looks promising but needs further investigation (Quality assessment: moderate; Recommendation: strong; Agreement: conditional) Four groups of pathophysiological mechanisms have been suggested to cause pain in chronic pancreatitis: 1) inflammation of the pancreas; 2) increased intrapancreatic pressure within the parenchyma and/or pancreatic duct, causing tissue ischemia; 3) (late) pancreatic and extrapancreatic complications (e.g. pseudocysts, portal thrombosis, bile duct/duodenal strictures and peptic ulcers) and 4) alterations indicative of nerve damage, e.g. increased number and diameter of pancreatic nerves, and inflammation of perineural sheathes have been described in chronic pancreatitis together with changes in the central nervous system (peripheral and central sensitization)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0060529", "ISSN" : "1932-6203", "PMID" : "23555989", "abstract" : "BACKGROUND Pancreatic neuritis is a histopathological hallmark of pancreatic neuropathy and correlates to abdominal neuropathic pain sensation in pancreatic adenocarcinoma (PCa) and chronic pancreatitis (CP). However, inflammatory cell subtypes that compose pancreatic neuritis and their correlation to the neuropathic pain syndrome in PCa and CP are yet unknown. METHODS Inflammatory cells within pancreatic neuritis lesions of patients with PCa (n = 20) and CP (n = 20) were immunolabeled and colorimetrically quantified with the pan-leukocyte marker CD45, with CD68 (macrophages), CD8 (cytotoxic T-lymphocytes), CD4 (T-helper cells), CD20 (B-lymphocytes), NCL-PC (plasma cells), neutrophil elastase, PRG2 (eosinophils), anti-mast cell (MC) tryptase and correlated to pain sensation. Perineural mast cell subtypes were analyzed by double immunolabeling with MC chymase. Expression and neural immunoreactivity of protease-activated receptor type 1 (PAR-1) and type 2 (PAR-2) were analyzed in PCa and CP and correlated to pain status of the patients. RESULTS In PCa and CP, nerves were predominantly infiltrated by cytotoxic T-lymphocytes (PCa: 35% of all perineural inflammatory cells, CP: 33%), macrophages (PCa: 39%, CP: 33%) and MC (PCa: 21%, CP: 27%). In both entities, neuropathic pain sensation was associated with a specific increase of perineural MC (PCa without pain: 14% vs. PCa with pain: 31%; CP without pain: 19% vs. CP with pain: 34%), not affecting the frequency of other inflammatory cell subtypes. The vast majority of these MC contained MC chymase. PAR-1 and PAR-2 expression did not correlate to the pain sensation of PCa and CP patients. CONCLUSION Pancreatic neuritis in PC and CP is composed of cytotoxic T-lymphocytes, macrophages and MC. The specific enrichment of MC around intrapancreatic nerves in neuropathic pain due to PCa and CP suggests the presence of MC-induced visceral hypersensitivity in the pancreas. Therefore, pancreatic and enteric neuropathies seem to share a similar type of neuro-immune interaction in the generation of visceral pain.", "author" : [ { "dropping-particle" : "", "family" : "Demir", "given" : "Ihsan Ekin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schorn", "given" : "Stephan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schremmer-Danninger", "given" : "Elisabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Kun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kehl", "given" : "Timo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giese", "given" : "Nathalia A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alg\u00fcl", "given" : "Hana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Friess", "given" : "Helmut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ceyhan", "given" : "G\u00fcralp O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "editor" : [ { "dropping-particle" : "", "family" : "Lo", "given" : "Anthony WI.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2013", "3", "28" ] ] }, "note" : "NULL", "page" : "e60529", "title" : "Perineural mast cells are specifically enriched in pancreatic neuritis and neuropathic pain in pancreatic cancer and chronic pancreatitis.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1053/j.gastro.2008.09.029", "ISSN" : "1528-0012", "PMID" : "18992743", "abstract" : "BACKGROUND & AIMS Chronic pancreatitis (CP) and pancreatic adenocarcinoma (PCa) are characterized by intrapancreatic neural alterations and pain. Our aims were to: (a) Investigate whether neuropathic changes like pancreatic neuritis, increased neural density, and hypertrophy are phenomena only in CP or whether they are also evident in other pancreatic disorders as well, (b) study possible variations in neural cancer cell invasion among malignant pancreatic tumors, and (c) explore whether these neuropathic changes contribute to pain sensation. METHODS Neuropathic changes were studied in PCa (n=149), in CP (n=141), in pancreatic tumors (PTm) including serous/mucinous cystadenomas, invasive/noninvasive intraductal papillary mucinous neoplasias, benign/malignant neuroendocrine tumors, ampullary cancers (n=196), and in normal pancreas (n=60). The results were correlated with GAP-43 expression, tissue inflammation, pancreatic neuritis, neural invasion, fibrosis, desmoplasia, pain, and patient survival. RESULTS Increased neural density and hypertrophy were only detected in PCa and CP and were strongly associated with GAP-43 over expression and abdominal pain. The severity of pancreatic neuritis was strongest in PCa and was closely linked to changes in neural density and hypertrophy. The aggressiveness of neural cancer cell invasion was most prominent in PCa and was related to neuropathic changes, desmoplasia, and pain. Severe and enduring pain were strongly associated with poor prognosis in PCa patients. CONCLUSIONS Enhanced neural density and hypertrophy are only typical features of CP and PCa among all investigated pancreatic disorders. Such neuropathic changes, including damage to nerves by inflammatory and/or cancer cells, seem to enhance and generate pancreatic neuropathic pain.", "author" : [ { "dropping-particle" : "", "family" : "Ceyhan", "given" : "G\u00fcralp O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergmann", "given" : "Frank", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kadihasanoglu", "given" : "Mustafa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Altintas", "given" : "Burak", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Demir", "given" : "Ihsan E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hinz", "given" : "Ulf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "M\u00fcller", "given" : "Michael W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giese", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "B\u00fcchler", "given" : "Markus W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giese", "given" : "Nathalia A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Friess", "given" : "Helmut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2009", "1" ] ] }, "note" : "NULL", "page" : "177-186.e1", "title" : "Pancreatic neuropathy and neuropathic pain--a comprehensive pathomorphological study of 546 cases.", "type" : "article-journal", "volume" : "136" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISSN" : "0016-5085", "PMID" : "3360267", "abstract" : "We sought to identify characteristics of pancreatic nerves that were altered in chronic pancreatitis. Pancreatic tissue removed from patients with chronic pancreatitis was analyzed for the number and size of nerves, their association with inflammatory infiltrates, and their fine structure. The mean diameter of nerves in these patients was significantly greater than in controls, whereas the mean area of tissue served per nerve was significantly less than in controls. Foci of inflammatory cells, prominent in some specimens, sometimes were associated with nerves and ganglia, but inflammatory foci and neural elements also existed separately. Invasion of nerve tissue by inflammatory cells was observed but was not massive. Ultrastructural changes were detected in nerves. Individual nerve fibers showed evidence of damage, and there was evidence of edema in the nerve bundle. The perineurial sheath was altered so that it no longer provided a barrier between the surrounding connective tissue and the internal neural components. The results of this study indicate that nerves are preferentially retained while parenchyma degenerates and is replaced by fibrosis during chronic pancreatitis, but that they are retained in an altered condition. Increased mean diameters of nerves in chronic pancreatitis argues against pain being caused by constriction due to fibrosis. It is likely that both sensory and motor nerve fibers are affected by this alteration.", "author" : [ { "dropping-particle" : "", "family" : "Bockman", "given" : "D E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buchler", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Malfertheiner", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beger", "given" : "H G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastroenterology", "id" : "ITEM-3", "issue" : "6", "issued" : { "date-parts" : [ [ "1988", "6" ] ] }, "note" : "NULL", "page" : "1459-69", "title" : "Analysis of nerves in chronic pancreatitis.", "type" : "article-journal", "volume" : "94" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.3748/wjg.v19.i42.7282", "ISSN" : "2219-2840", "PMID" : "24259959", "abstract" : "Despite multiple theories on the pathogenesis of pain in chronic pancreatitis, no uniform and consistently successful treatment strategy exists and abdominal pain still remains the dominating symptom for most patients and a major challenge for clinicians. Traditional theories focussed on a mechanical cause of pain related to anatomical changes and evidence of increased ductal and interstitial pressures. These observations form the basis for surgical and endoscopic drainage procedures, but the outcome is variable and often unsatisfactory. This underscores the fact that other factors must contribute to pathogenesis of pain, and has shifted the focus towards a more complex neurobiological understanding of pain generation. Amongst other explanations for pain, experimental and human studies have provided evidence that pain perception at the peripheral level and central pain processing of the nociceptive information is altered in patients with chronic pancreatitis, and resembles that seen in neuropathic and chronic pain disorders. However, pain due to e.g., complications to the disease and adverse effects to treatment must not be overlooked as an additional source of pain. This review outlines the current theories on pain generation in chronic pancreatitis which is crucial in order to understand the complexity and limitations of current therapeutic approaches. Furthermore, it may also serve as an inspiration for further research and development of methods that can evaluate the relative contribution and interplay of different pain mechanisms in the individual patients, before they are subjected to more or less empirical treatment.", "author" : [ { "dropping-particle" : "", "family" : "Poulsen", "given" : "Jakob Lykke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olesen", "given" : "S\u00f8ren Schou", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Malver", "given" : "Lasse Paludan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fr\u00f8kj\u00e6r", "given" : "Jens Br\u00f8ndum", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn Mohr", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "World journal of gastroenterology", "id" : "ITEM-4", "issue" : "42", "issued" : { "date-parts" : [ [ "2013", "11", "14" ] ] }, "note" : "NULL", "page" : "7282-91", "title" : "Pain and chronic pancreatitis: a complex interplay of multiple mechanisms.", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.3748/wjg.v21.i1.47", "ISSN" : "2219-2840", "PMID" : "25574079", "abstract" : "Pain in chronic pancreatitis (CP) shows similarities with other visceral pain syndromes (i.e., inflammatory bowel disease and esophagitis), which should thus be managed in a similar fashion. Typical causes of CP pain include increased intrapancreatic pressure, pancreatic inflammation and pancreatic/extrapancreatic complications. Unfortunately, CP pain continues to be a major clinical challenge. It is recognized that ongoing pain may induce altered central pain processing, e.g., central sensitization or pro-nociceptive pain modulation. When this is present conventional pain treatment targeting the nociceptive focus, e.g., opioid analgesia or surgical/endoscopic intervention, often fails even if technically successful. If central nervous system pain processing is altered, specific treatment targeting these changes should be instituted (e.g., gabapentinoids, ketamine or tricyclic antidepressants). Suitable tools are now available to make altered central processing visible, including quantitative sensory testing, electroencephalograpy and (functional) magnetic resonance imaging. These techniques are potentially clinically useful diagnostic tools to analyze central pain processing and thus define optimum management approaches for pain in CP and other visceral pain syndromes. The present review proposes a systematic mechanism-orientated approach to pain management in CP based on a holistic view of the mechanisms involved. Future research should address the circumstances under which central nervous system pain processing changes in CP, and how this is influenced by ongoing nociceptive input and therapies. Thus we hope to predict which patients are at risk for developing chronic pain or not responding to therapy, leading to improved treatment of chronic pain in CP and other visceral pain disorders.", "author" : [ { "dropping-particle" : "", "family" : "Bouwense", "given" : "Stefan A W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vries", "given" : "Marjan", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schreuder", "given" : "Luuk T W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olesen", "given" : "S\u00f8ren S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fr\u00f8kj\u00e6r", "given" : "Jens B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goor", "given" : "Harry", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "Oliver H G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "World journal of gastroenterology", "id" : "ITEM-5", "issue" : "1", "issued" : { "date-parts" : [ [ "2015", "1", "7" ] ] }, "page" : "47-59", "title" : "Systematic mechanism-orientated approach to chronic pancreatitis pain.", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(42,103,199,321,322)", "plainTextFormattedCitation" : "(42,103,199,321,322)", "previouslyFormattedCitation" : "(42,103,199,321,322)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(42,103,199,321,322). How these different pathophysiological mechanisms exactly cause pain in chronic pancreatitis and which correct time point for surgerical procedures is most appropriate are still under debate. In many centres invasive treatment is recommended in patients where pain cannot be controlled without the use of opioids and endoscopic interventions have failed or are not indicated. Although long-term results of surgery are promising, most of studies to date are observational or only compare different invasive procedures. Question if surgery, when performed early, is better than opioid treatment or early endoscopy cannot be answered till now. The different studies have also compared surgical techniques or surgery vs. Endoscopy, and as no studies have used a sham control the natural history of disease and placebo effects have not been taken into consideration and data must be interpreted causiously. Surgical options for pain are classified into three categories: a) decompression (focusing on ductal hypertension), b) resection (focusing on inflammatory masses and stones in the pancreatic head) and c) mixed techniques. In the 1950s, Puestow and Gillesby developed a technique combining a longitudinal opening of the pancreatic duct and an anastomosis to the small intestine with a pancreatic left resection which is still applied nowadays for pancreatic stones and pseudocysts. Another technique by Partington and Rochelle is a modificaton of this procedure with an extended opening of the pancreatic duct and a preservation of the pancreatic tail. Surgical procedures for painful CP aim at the resection of the pancreatic inflammatory mass, such as (1) the standard Kausch-Whipple procedure with resection of the pancreatic head, gallbladder, duodenum, and gastric antrum, (2) the Traverso-Longmire procedure, a pylorus-preserving pancreaticoduodenectomy, (3) the Beger procedure, a resection of the pancreatic head that preserves the duodenum and intrapancreatic bile duct by subtotally excising the head and uncinate process, (4) the Frey procedure, a variation of the Beger procedure that combines longitudinal pancreaticojejunostomy with a local pancreatic head excision without transection of the pancreas above the portal vein, (5) the Berne/Farkas technique, a partial resection of the pancreatic head without a lateral pancreaticojejunostomy that avoids the transection of the pancreas above the portal vein and combines the advantages of the Beger and Frey operations. Depending on pathology and location, other organ-preserving procedures include (6) the “V-shape excision“ of the ventral pancreas, (7) the middle segmental pancreatic resection, (8) the pancreatic left resection or (9) total pancreatectomy. Data on early surgical intervention might be associated with improved postoperative pain relief compared to delayed surgery after repeated endoscopic interventionsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s11605-014-2571-8", "ISSN" : "1873-4626", "PMID" : "24944153", "abstract" : "BACKGROUND Surgical intervention has traditionally been reserved as the last management option for pain in chronic pancreatitis. Recently, there has been a call for surgery to be offered earlier in the disease process. The objectives of this review were to evaluate the effect of early surgery on postoperative pain, pancreatic function, and re-intervention rates in chronic pancreatitis. METHODS A systematic literature search through EMBASE, Cochrane Review, and PubMed from January 1950 to January 2014 was conducted. Citations found in relevant papers are hand-searched. Data which could be pooled were analyzed using Revman (v5.2). Risk of bias analysis was conducted. RESULTS Of the 2,886 potentially eligible studies identified, 11 studies met the inclusion criteria. There was large heterogeneity in the study designs, and studies were conducted over a lengthy time span. Seven studies examined pain, three studies examined pancreatic function, and three studies examined rates of re-intervention. Meta-analysis of the three studies with comparative raw data regarding complete pain relief showed that early surgery was associated with an increased likelihood of complete postoperative pain relief (RR\u2009=\u20091.67, 95% CI 1.09-2.56, p\u2009=\u20090.02). Early surgery was also associated with reduced risk of pancreatic insufficiency and low re-intervention rates. CONCLUSIONS Data from this study supports considering early surgery for pain management in patients with chronic pancreatitis, with the potential of a reduced risk of pancreatic insufficiency and the need for further intervention. Further prospective randomized studies are warranted comparing early surgery against conservative step-up approaches.", "author" : [ { "dropping-particle" : "", "family" : "Yang", "given" : "Catherine J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bliss", "given" : "Lindsay A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schapira", "given" : "Emily F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freedman", "given" : "Steven D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Sing Chau", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Windsor", "given" : "John A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tseng", "given" : "Jennifer F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2014", "10", "19" ] ] }, "note" : "NULL", "page" : "1863-9", "title" : "Systematic review of early surgery for chronic pancreatitis: impact on pain, pancreatic function, and re-intervention.", "type" : "article-journal", "volume" : "18" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(323)", "plainTextFormattedCitation" : "(323)", "previouslyFormattedCitation" : "(323)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(323). A randomized trial on early surgery compared to the ?normal’ step-up approach (medication, followed by endoscopy and finally surgery when needed) has nearly finished and will provide us with data on the timing of surgery in chronic pancreatitisADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1186/1471-230X-13-49", "ISSN" : "1471-230X", "PMID" : "23506415", "abstract" : "BACKGROUND In current practice, patients with chronic pancreatitis undergo surgical intervention in a late stage of the disease, when conservative treatment and endoscopic interventions have failed. Recent evidence suggests that surgical intervention early on in the disease benefits patients in terms of better pain control and preservation of pancreatic function. Therefore, we designed a randomized controlled trial to evaluate the benefits, risks and costs of early surgical intervention compared to the current stepwise practice for chronic pancreatitis. METHODS/DESIGN The ESCAPE trial is a randomized controlled, parallel, superiority multicenter trial. Patients with chronic pancreatitis, a dilated pancreatic duct (\u22655 mm) and moderate pain and/or frequent flare-ups will be registered and followed monthly as potential candidates for the trial. When a registered patient meets the randomization criteria (i.e. need for opioid analgesics) the patient will be randomized to either early surgical intervention (group A) or optimal current step-up practice (group B). An expert panel of chronic pancreatitis specialists will oversee the assessment of eligibility and ensure that allocation to either treatment arm is possible. Patients in group A will undergo pancreaticojejunostomy or a Frey-procedure in case of an enlarged pancreatic head (\u22654 cm). Patients in group B will undergo a step-up practice of optimal medical treatment, if needed followed by endoscopic interventions, and if needed followed by surgery, according to predefined criteria. Primary outcome is pain assessed with the Izbicki pain score during a follow-up of 18 months. Secondary outcomes include complications, mortality, total direct and indirect costs, quality of life, pancreatic insufficiency, alternative pain scales, length of hospital admission, number of interventions and pancreatitis flare-ups. For the sample size calculation we defined a minimal clinically relevant difference in the primary endpoint as a difference of at least 15 points on the Izbicki pain score during follow-up. To detect this difference a total of 88 patients will be randomized (alpha 0.05, power 90%, drop-out 10%). DISCUSSION The ESCAPE trial will investigate whether early surgery in chronic pancreatitis is beneficial in terms of pain relief, pancreatic function and quality of life, compared with current step-up practice. TRIAL REGISTRATION ISRCTN: ISRCTN45877994.", "author" : [ { "dropping-particle" : "", "family" : "Ahmed Ali", "given" : "Usama", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Issa", "given" : "Yama", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruno", "given" : "Marco J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goor", "given" : "Harry", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Santvoort", "given" : "Hjalmar", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Busch", "given" : "Olivier R C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dejong", "given" : "Cornelis H C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nieuwenhuijs", "given" : "Vincent B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eijck", "given" : "Casper H", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dullemen", "given" : "Hendrik M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fockens", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siersema", "given" : "Peter D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gouma", "given" : "Dirk J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hooft", "given" : "Jeanin E", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keulemans", "given" : "Yolande", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Poley", "given" : "Jan W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Timmer", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Besselink", "given" : "Marc G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vleggaar", "given" : "Frank P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "Oliver H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gooszen", "given" : "Hein G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dijkgraaf", "given" : "Marcel G W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boermeester", "given" : "Marja A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dutch Pancreatitis Study Group", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMC gastroenterology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2013", "3", "18" ] ] }, "note" : "NULL", "page" : "49", "title" : "Early surgery versus optimal current step-up practice for chronic pancreatitis (ESCAPE): design and rationale of a randomized trial.", "type" : "article-journal", "volume" : "13" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(324)", "plainTextFormattedCitation" : "(324)", "previouslyFormattedCitation" : "(324)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(324). In several randomized controlled trials, tailored organ-sparing procedures, such as the Beger or Frey procedures, have been found to be superior to the classic Whipple or the pylorus-preserving Whipple procedure in regard to pain relief (75%) and morbidity (20%)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0002-9610", "PMID" : "7818000", "abstract" : "BACKGROUND In about 30% of patients, chronic pancreatitis leads to an inflammatory enlargement of the pancreatic head with subsequent obstruction of the pancreatic duct, common bile duct, and duodenum. METHODS In a prospective, randomized controlled trial, we compared duodenum-preserving pancreatic head resection (DPPHR) with pylorus-preserving Whipple (PPW) operation to define the advantages of each operation with regard to (1) postoperative complications, (2) glucose tolerance and induction of diabetes mellitus, and (3) postoperative pain and quality of life up to 6 months after operation for chronic pancreatitis. RESULTS The two study groups of 20 patients were both well balanced with regard to sex, age, history of chronic pancreatitis, and indication for surgery. Postoperative mortality was zero. After duodenum-preserving and pylorus-preserving resection, morbidity was 15% and 20%, respectively. After 6 months, patients who underwent the duodenum-preserving resection had less pain, greater weight gain, a better glucose tolerance, and a higher insulin secretion capacity. CONCLUSION The DPPHR compares favorably with the standard PPW operation and should be considered as an alternative procedure in the treatment of chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "B\u00fcchler", "given" : "M W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Friess", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "M\u00fcller", "given" : "M W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wheatley", "given" : "A M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beger", "given" : "H G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American journal of surgery", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "1995", "1" ] ] }, "note" : "NULL", "page" : "65-9; discussion 69-70", "title" : "Randomized trial of duodenum-preserving pancreatic head resection versus pylorus-preserving Whipple in chronic pancreatitis.", "type" : "article-journal", "volume" : "169" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.surg.2012.05.016", "ISSN" : "1532-7361", "PMID" : "22906892", "abstract" : "BACKGROUND Individualization of operations for chronic pancreatitis (CP) offers tailored operative approaches for the management of complications of CP. For the management of the inflammatory head mass and its complications, duodenum-preserving procedures (Frey and Beger operations) compete in efficacy and quality of life with pancreatoduodenectomy procedures (PPPD and Whipple operations). Our aim was to compare the short- and long-term results of duodenum-preserving and duodenum-resecting techniques in a prospective, randomized trial. METHODS Eighty-five patients with CP were randomized to undergo either pylorus-preserving (PPPD) or duodenum-preserving pancreatic head resection (DPPHR). Perioperative and long term results were evaluated. RESULTS Although the duodenum-preserving operations had a lesser median operating time (360 vs 435 minutes; P = .002), there were no differences in the need for intraoperative blood transfusion (76% vs 79%) or the duration of hospital stay (13 vs 14 days). Postoperative complications in general (33% vs 30%), surgical complications (21% vs 23%), and severe complications such as pancreatic leakage (10% vs 5%) or the need for reoperation (2% vs 2%) did not differ between the DPPHR and the PPPD groups, and there was no mortality (0%). The long-term outcome after a median of >5 years showed no differences between the DPPHR and PPPD regarding quality of life, pain control (67% vs 67%), endocrine status (45% vs 44%), and exocrine insufficiency (76% vs 61%). CONCLUSION Both types of pancreatic head resections are equally effective in pain relief and eventual quality of life after long-term follow-up (>5 years) without differences in endocrine or exocrine function.", "author" : [ { "dropping-particle" : "", "family" : "Keck", "given" : "Tobias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adam", "given" : "Ulrich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Makowiec", "given" : "Frank", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Riediger", "given" : "Hartwig", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wellner", "given" : "Ulrich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tittelbach-Helmrich", "given" : "Dietlind", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hopt", "given" : "Ulrich T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Surgery", "id" : "ITEM-2", "issue" : "3 Suppl 1", "issued" : { "date-parts" : [ [ "2012", "9" ] ] }, "note" : "NULL", "page" : "S95-S102", "title" : "Short- and long-term results of duodenum preservation versus resection for the management of chronic pancreatitis: a prospective, randomized study.", "type" : "article-journal", "volume" : "152" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(325,326)", "plainTextFormattedCitation" : "(325,326)", "previouslyFormattedCitation" : "(325,326)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(325,326). In addition, independent randomized trials revealed that the Frey procedure provides a better quality of life, while the pylorus-preserving pancreaticoduodenectomy and the Frey procedure were found effective in long term pain relief (82-100%) and morbidity (17%)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0044-409X", "PMID" : "7778342", "abstract" : "AIM OF THE STUDY To evaluate the efficacy of duodenum-preserving resections of the head of the pancreas in the treatment of chronic pancreatitis this study was devised. So far studies on the natural course and the different therapeutic approaches have primarily focused on pain measurement in rough categories and hard data as mortality and morbidity. In this study the improvement of the quality of life was assessed to determine the therapeutic success of both procedures. PATIENTS AND METHODS In a prospective randomized study 24 patients underwent either Beger's (n = 11) or Frey's procedure (n = 13) so far. 15 patients suffered from distal common bile duct stenosis, 2 from segmental duodenal stenosis, 4 from segmental portal hypertension, and one from pancreato-pleural fistula. The quality of life questionnaire of the European Organization for Research and Treatment of Cancer was assessed before surgery and during follow-up. The multidimensional questionnaire incorporates functional scales (physical, cognitive, emotional, and social), symptom scales (fatigue, pain, dyspnea, loss of appetite, sleep disturbance, obstipation, diarrhea, nausea, and vomiting), and a global quality of life scale. Follow-up was 12 months in all patients. RESULTS There was no postoperative mortality in neither group. Postoperative morbidity was 17% (n = 2 in either group). This included one transitory common bile duct stenosis, one bronchopneumonia, and two postoperative bleedings which were treated conservatively. The pain index was reduced by 94% in the Beger- and 90% in the Frey group. The physical status, working ability, emotional and social functioning, and global quality of life score had significantly improved by 46%, 50%, 69%, 60%, and 67% in the Beger group and by 38%, 50%, 64%, 80%, and 67% in the Frey group. CONCLUSION The duodenum-preserving resections of the head of the pancreas according to Beger and Frey are equivalently safe and effective. Both techniques result in a significant improvement of the patients' quality of life.", "author" : [ { "dropping-particle" : "", "family" : "Izbicki", "given" : "J R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Knoefel", "given" : "W T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bloechle", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "K\u00fcchler", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "K\u00fchn", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Limmer", "given" : "J C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Broelsch", "given" : "C E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Zentralblatt fur Chirurgie", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "1995" ] ] }, "note" : "NULL", "page" : "298-305", "title" : "[The status of duodenum-preserving resection of the head of the pancreas in therapy of chronic pancreatitis].", "type" : "article-journal", "volume" : "120" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0003-4932", "PMID" : "9860476", "abstract" : "OBJECTIVE To analyze the efficacy of extended drainage--that is, longitudinal pancreaticojejunostomy combined with local pancreatic head excision (LPJ-LPHE)-and pylorus-preserving pancreatoduodenectomy (PPPD) in terms of pain relief, control of complications arising from adjacent organs, and quality of life. SUMMARY BACKGROUND DATA Based on the hypotheses of pain origin (ductal hypertension and perineural inflammatory infiltration), drainage and resection constitute the main principles of surgery for chronic pancreatitis. METHODS Sixty-one patients were randomly allocated to either LPJ-LPHE (n = 31) or PPPD (n = 30). The interval between symptoms and surgery ranged from 12 months to 10 years (mean 5.1 years). In addition to routine pancreatic diagnostic workup, a multidimensional psychometric quality-of-life questionnaire and a pain score were used. Endocrine and exocrine functions were assessed in terms of oral glucose tolerance and serum concentrations of insulin, C-peptide, and HbA1c, as well as fecal chymotrypsin and pancreolauryl testing. During a median follow-up of 24 months (range 12 to 36), patients were reassessed in the outpatient clinic. RESULTS One patient died of cardiovascular failure in the LPJ-LPHE group (3.2%); there were no deaths in the PPPD group. Overall, the rate of in-hospital complications was 19.4% in the LPJ-LPHE group and 53.3% in the PPPD group, including delayed gastric emptying in 9 of 30 patients (30%; p < 0.05). Complications of adjacent organs were definitively resolved in 93.5% in the LPJ-LPHE group and in 100% in the PPPD group. The pain score decreased by 94% after LPJ-LPHE and by 95% after PPPD. Global quality of life improved by 71% in the LPJ-LPHE group and by 43% in the PPPD group (p < 0.01). CONCLUSIONS Both procedures are equally effective in terms of pain relief and definitive control of complications affecting adjacent organs, but extended drainage by LPJ-LPHE provides a better quality of life.", "author" : [ { "dropping-particle" : "", "family" : "Izbicki", "given" : "J R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bloechle", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Broering", "given" : "D C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Knoefel", "given" : "W T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuechler", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Broelsch", "given" : "C E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of surgery", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "1998", "12" ] ] }, "note" : "NULL", "page" : "771-9", "title" : "Extended drainage versus resection in surgery for chronic pancreatitis: a prospective randomized trial comparing the longitudinal pancreaticojejunostomy combined with local pancreatic head excision with the pylorus-preserving pancreatoduodenectomy.", "type" : "article-journal", "volume" : "228" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(327,328)", "plainTextFormattedCitation" : "(327,328)", "previouslyFormattedCitation" : "(327,328)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(327,328). Long-term follow-up showed comparable pain control and pancreatic function between both procedures, while survival rates were superior after the Frey procedure. In a prospective, randomized trial on different techniques of duodenum-preserving pancreatic head resection, the Beger and the Frey procedures were found to be equally safe and effective in pain reliefADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0003-4932", "PMID" : "7726670", "abstract" : "OBJECTIVE Two techniques of duodenum-preserving resection of the head of the pancreas were compared in a prospective, randomized trial. The technical feasibility and effects on quality of life were assessed. SUMMARY BACKGROUND DATA Drainage and resection are the principles of surgery in chronic pancreatitis. The techniques of duodenum-preserving resection of the head of the pancreas as described by Berger and Frey combine both to different degrees. The efficacy of both procedures has not been compared thus far. METHODS Forty-two patients were allocated randomly to either Beger's (n = 20) or Frey's (n = 22) group. In addition to routine pancreatic diagnostic work-up, a multidimensional psychometric quality-of-life questionnaire and and a pain score were used. Assessment of endocrine and exocrine function included oral glucose tolerance test, serum concentrations of insulin, C-peptide, and HbA1c, as well as fecal chymotrypsin and pancreolauryl test. The interval between symptoms and surgery ranged from 12 months to 12 years, with a mean of 5.7 years. The mean follow-up was 1.5 years. RESULTS There was no mortality. Overall morbidity was 14% (20% Beger, 9% Frey). Complications from adjacent organs were resolved definitively in 94% (90% Beger, 100% Frey). A decrease of 95% and 94% of the pain score after Beger's and Frey's procedure, respectively, and an increase of 67% of the overall quality-of-life index in both groups were observed. Endocrine and exocrine function did not differ between both groups. CONCLUSIONS Both techniques of duodenum-preserving resection of the head of the pancreas are equally safe and effective with regard to pain relief, improvement of quality of life, and definitive control of complications affecting adjacent organs. Neither procedure leads to further deterioration of endocrine and exocrine pancreatic function.", "author" : [ { "dropping-particle" : "", "family" : "Izbicki", "given" : "J R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bloechle", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Knoefel", "given" : "W T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuechler", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Binmoeller", "given" : "K F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Broelsch", "given" : "C E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of surgery", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "1995", "4" ] ] }, "note" : "NULL", "page" : "350-8", "title" : "Duodenum-preserving resection of the head of the pancreas in chronic pancreatitis. A prospective, randomized trial.", "type" : "article-journal", "volume" : "221" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(329)", "plainTextFormattedCitation" : "(329)", "previouslyFormattedCitation" : "(329)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(329). About ten years later, a long-term follow-up showed no difference in pain control within the two groupsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0003-4932", "PMID" : "15798460", "abstract" : "OBJECTIVE To report on the long-term follow-up of a randomized clinical trial comparing pancreatic head resection according to Beger and limited pancreatic head excision combined with longitudinal pancreatico-jejunostomy according to Frey for surgical treatment of chronic pancreatitis. SUMMARY BACKGROUND DATA Resection and drainage are the 2 basic surgical principles in surgical treatment of chronic pancreatitis. They are combined to various degrees by the classic duodenum preserving pancreatic head resection (Beger) and limited pancreatic head excision combined with longitudinal pancreatico-jejunostomy (Frey). These procedures have been evaluated in a randomized controlled trial by our group. Long-term follow up has not been reported so far. METHODS Seventy-four patients suffering from chronic pancreatitis were initially allocated to DPHR (n = 38) or LE (n = 36). This postoperative follow-up included the following parameters: mortality, quality of life (QL), pain (validated pain score), and exocrine and endocrine function. RESULTS Median follow-up was 104 months (72-144). Seven patients were not available for follow-up (Beger = 4; Frey = 3). There was no significant difference in late mortality (31% [8/26] versus 32% [8/25]). No significant differences were found regarding QL (global QL 66.7 [0-100] versus 58.35 [0-100]), pain score (11.25 [0-75] versus 11.25 [0-99.75]), exocrine (88% versus 78%) or endocrine insufficiency (56% versus 60%). CONCLUSIONS After almost 9 years' long-term follow-up, there was no difference regarding mortality, quality of life, pain, or exocrine or endocrine insufficiency within the 2 groups. The decision which procedure to choose should be based on the surgeon's experience.", "author" : [ { "dropping-particle" : "", "family" : "Strate", "given" : "Tim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Taherpour", "given" : "Zohre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bloechle", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mann", "given" : "Oliver", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruhn", "given" : "Jens P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schneider", "given" : "Claus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuechler", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yekebas", "given" : "Emre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Izbicki", "given" : "Jakob R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of surgery", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2005", "4" ] ] }, "note" : "NULL", "page" : "591-8", "title" : "Long-term follow-up of a randomized trial comparing the beger and frey procedures for patients suffering from chronic pancreatitis.", "type" : "article-journal", "volume" : "241" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(330)", "plainTextFormattedCitation" : "(330)", "previouslyFormattedCitation" : "(330)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(330). In addition, a controlled, prospective, randomized study on the evaluation of the Beger and Berne procedures for CP showed the Berne technique to provide significantly shorter operation times and hospital stays, while the quality of life was found to be similarADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.surg.2007.12.002", "ISSN" : "1532-7361", "PMID" : "18374046", "abstract" : "OBJECTIVE A prospective, randomized study was performed to evaluate two variations of the duodenum-preserving pancreatic head resection (DPPHR), either with (Beger procedure) or without (Berne modification) the division of the pancreas anterior to the portal vein, in patients with chronic pancreatitis. METHODS Randomized, controlled, patient-blinded trial of patients with inflammatory pancreatic head tumors. The primary endpoint was the duration of surgery. Other a priori-ordered endpoints were length of ICU stay, postoperative complication, length of hospital stay, and quality of life after 24 months. RESULTS Sixty-five patients were randomized to the Berne or Beger procedures. The Berne modification could be performed faster (46 minutes difference, P < .05). The median length of stay on the ICU was one day in both groups (P = .97) but the median hospital stay was shorter in the Berne group (11 (8-39) versus 15 (8-47); P = .015). The quality of life two years after surgery did not differ significantly between the two groups (EORTC-QLQ-C30, Beger 65.6% vs. Berne 71.3%, P = .371). Three patients who had received the Berne procedure were reoperated on during the follow-up period due to ongoing pancreatitis and bile duct obstruction (P = .22). CONCLUSION The Berne technique is technically simpler compared with the original Beger procedure, reflected in its significantly shorter operation times and hospital stays. The quality of life is similar after both procedures. The Berne modification of DPPHR adds to our panel of surgical procedures that can be applied with effective early and late outcomes.", "author" : [ { "dropping-particle" : "", "family" : "K\u00f6ninger", "given" : "J\u00f6rg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seiler", "given" : "Christoph M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sauerland", "given" : "Stefan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wente", "given" : "Moritz N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reidel", "given" : "Margot A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "M\u00fcller", "given" : "Michael W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Friess", "given" : "Helmut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "B\u00fcchler", "given" : "Markus W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Surgery", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2008", "4" ] ] }, "note" : "NULL", "page" : "490-8", "title" : "Duodenum-preserving pancreatic head resection--a randomized controlled trial comparing the original Beger procedure with the Berne modification (ISRCTN No. 50638764).", "type" : "article-journal", "volume" : "143" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(331)", "plainTextFormattedCitation" : "(331)", "previouslyFormattedCitation" : "(331)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(331). However, ten-year follow-up did not show any differences in patient-relevant outcome parameters between the Beger and Berne proceduresADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.surg.2016.02.028", "ISSN" : "1532-7361", "PMID" : "27106794", "abstract" : "BACKGROUND Since the introduction of the duodenum-preserving pancreatic head resection for operative treatment of chronic pancreatitis, various modifications of the original Beger procedure have emerged. A randomized controlled trial comparing the Beger procedure and the Berne modification indicated that the latter is an equivalent alternative, but a comparison of the long-term results of both procedures has not yet been published. METHODS Between December 2002 and January 2005, 65 patients were randomized intraoperatively to the Beger or the Berne procedure. For this 10-year follow-up, patients were contacted by phone and in writing to evaluate patient-relevant outcome parameters. Statistical analysis was made on an intention-to-treat basis. RESULTS Median follow-up was 129 (111-137) months. Forty of 65 patients were available for follow-up; 11 of the original study cohort had died, and 14 were otherwise lost to follow-up. Quality of life, pain, occupational disability, exocrine and endocrine pancreatic function, endoscopic interventions, and redo operations were comparable in both groups. More than half of the patients were completely free of pain, and the majority in both groups judged that the index operation had improved their quality of life. CONCLUSION Ten-year follow-up showed no differences in patient-relevant outcome parameters between the Beger and Berne procedures for treatment of chronic pancreatitis. Because short-term results have shown the Berne modification is superior in terms of operation time and duration of hospital stay, it should be preferred whenever possible, depending on the individual surgeon's expertise and the intraoperative findings.", "author" : [ { "dropping-particle" : "", "family" : "Klaiber", "given" : "Ulla", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alldinger", "given" : "Ingo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Probst", "given" : "Pascal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruckner", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Contin", "given" : "Pietro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "K\u00f6ninger", "given" : "J\u00f6rg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hackert", "given" : "Thilo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "B\u00fcchler", "given" : "Markus W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Diener", "given" : "Markus K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Surgery", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2016", "7" ] ] }, "note" : "NULL", "page" : "127-35", "title" : "Duodenum-preserving pancreatic head resection: 10-year follow-up of a randomized controlled trial comparing the Beger procedure with the Berne modification.", "type" : "article-journal", "volume" : "160" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(332)", "plainTextFormattedCitation" : "(332)", "previouslyFormattedCitation" : "(332)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(332). In a randomized trial on pylorus-preserving and duodenum-preserving pancreatic head resections, both types of resections were found to be equally effective in pain relief and quality of life without differences in exocrine or endocrine pancreatic functionADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.surg.2012.05.016", "ISSN" : "1532-7361", "PMID" : "22906892", "abstract" : "BACKGROUND Individualization of operations for chronic pancreatitis (CP) offers tailored operative approaches for the management of complications of CP. For the management of the inflammatory head mass and its complications, duodenum-preserving procedures (Frey and Beger operations) compete in efficacy and quality of life with pancreatoduodenectomy procedures (PPPD and Whipple operations). Our aim was to compare the short- and long-term results of duodenum-preserving and duodenum-resecting techniques in a prospective, randomized trial. METHODS Eighty-five patients with CP were randomized to undergo either pylorus-preserving (PPPD) or duodenum-preserving pancreatic head resection (DPPHR). Perioperative and long term results were evaluated. RESULTS Although the duodenum-preserving operations had a lesser median operating time (360 vs 435 minutes; P = .002), there were no differences in the need for intraoperative blood transfusion (76% vs 79%) or the duration of hospital stay (13 vs 14 days). Postoperative complications in general (33% vs 30%), surgical complications (21% vs 23%), and severe complications such as pancreatic leakage (10% vs 5%) or the need for reoperation (2% vs 2%) did not differ between the DPPHR and the PPPD groups, and there was no mortality (0%). The long-term outcome after a median of >5 years showed no differences between the DPPHR and PPPD regarding quality of life, pain control (67% vs 67%), endocrine status (45% vs 44%), and exocrine insufficiency (76% vs 61%). CONCLUSION Both types of pancreatic head resections are equally effective in pain relief and eventual quality of life after long-term follow-up (>5 years) without differences in endocrine or exocrine function.", "author" : [ { "dropping-particle" : "", "family" : "Keck", "given" : "Tobias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adam", "given" : "Ulrich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Makowiec", "given" : "Frank", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Riediger", "given" : "Hartwig", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wellner", "given" : "Ulrich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tittelbach-Helmrich", "given" : "Dietlind", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hopt", "given" : "Ulrich T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Surgery", "id" : "ITEM-1", "issue" : "3 Suppl 1", "issued" : { "date-parts" : [ [ "2012", "9" ] ] }, "note" : "NULL", "page" : "S95-S102", "title" : "Short- and long-term results of duodenum preservation versus resection for the management of chronic pancreatitis: a prospective, randomized study.", "type" : "article-journal", "volume" : "152" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(326)", "plainTextFormattedCitation" : "(326)", "previouslyFormattedCitation" : "(326)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(326). An indication for total pancreatectomy (with/without islet autotransplantation) is to palliate pain, especially after diabetes mellitus has developed. If performed early the clinical results of total pancreatectomy on pain relief look promising. Further trials are needed to provide high grade evidence on timing and efficacy of this procedureADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.pan.2013.10.009", "ISSN" : "1424-3911", "PMID" : "24555976", "abstract" : "DESCRIPTION Total pancreatectomy with islet autotransplantation (TPIAT) is a surgical procedure used to treat severe complications of chronic pancreatitis or very high risk of pancreatic cancer while reducing the risk of severe diabetes mellitus. However, clear guidance on indications, contraindications, evaluation, timing, and follow-up are lacking. METHODS A working group reviewed the medical, psychological, and surgical options and supporting literature related to TPIAT for a consensus meeting during PancreasFest. RESULTS Five major areas requiring clinical evaluation and management were addressed: These included: 1) indications for TPIAT; 2) contraindications for TPIAT; 3) optimal timing of the procedure; 4) need for a multi-disciplinary team and the roles of the members; 5) life-long management issues following TPIAP including diabetes monitoring and nutrition evaluation. CONCLUSIONS TPIAT is an effective method of managing the disabling complications of chronic pancreatitis and risk of pancreatic cancer in very high risk patients. Careful evaluation and long-term management of candidate patients by qualified multidisciplinary teams is required. Multiple recommendations for further research were also identified.", "author" : [ { "dropping-particle" : "", "family" : "Bellin", "given" : "Melena D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freeman", "given" : "Martin L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gelrud", "given" : "Andres", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slivka", "given" : "Adam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clavel", "given" : "Alfred", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Humar", "given" : "Abhinav", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwarzenberg", "given" : "Sarah J", 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[et al.]", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2014", "1" ] ] }, "note" : "NULL", "page" : "27-35", "title" : "Total pancreatectomy and islet autotransplantation in chronic pancreatitis: recommendations from PancreasFest.", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1097/SLA.0000000000001453", "ISSN" : "1528-1140", "PMID" : "26366540", "abstract" : "OBJECTIVE Our objective was to analyze factors predicting outcomes after a total pancreatectomy and islet autotransplantation (TP-IAT). BACKGROUND Chronic pancreatitis (CP) is increasingly treated by a TP-IAT. Postoperative outcomes are generally favorable, but a minority of patients fare poorly. METHODS In our single-centered study, we analyzed the records of 581 patients with CP who underwent a TP-IAT. Endpoints included persistent postoperative \"pancreatic pain\" similar to preoperative levels, narcotic use for any reason, and islet graft failure at 1 year. RESULTS In our patients, the duration (mean\u200a\u00b1\u200aSD) of CP before their TP-IAT was 7.1\u200a\u00b1\u200a0.3 years and narcotic usage of 3.3\u200a\u00b1\u200a0.2 years. Pediatric patients had better postoperative outcomes. Among adult patients, the odds of narcotic use at 1 year were increased by previous endoscopic retrograde cholangiopancreatography (ERCP) and stent placement, and a high number of previous stents (>3). Independent risk factors for pancreatic pain at 1 year were pancreas divisum, previous body mass index >30, and a high number of previous stents (>3). The strongest independent risk factor for islet graft failure was a low islet yield-in islet equivalents (IEQ)-per kilogram of body weight. We noted a strong dose-response relationship between the lowest-yield category (<2000 IEQ) and the highest (\u22655000 IEQ or more). Islet graft failure was 25-fold more likely in the lowest-yield category. CONCLUSIONS This article represents the largest study of factors predicting outcomes after a TP-IAT. 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ADDIN EN.CITE.DATA Important phenomenon in chronic pain disorders like chronic pancreatitis is the change in central nervous system pain processing like peripheral and central sensitization. When sensitization is present painful stimuli become more painful and endoscopic and/or surgical therapy has a higher risk of failure. Factors that are relevant in developing sensitization are duration of the disease, age, pain history and previous invasive treatmentADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3748/wjg.v21.i1.47", "ISSN" : "2219-2840", "PMID" : "25574079", "abstract" : "Pain in chronic pancreatitis (CP) shows similarities with other visceral pain syndromes (i.e., inflammatory bowel disease and esophagitis), which should thus be managed in a similar fashion. Typical causes of CP pain include increased intrapancreatic pressure, pancreatic inflammation and pancreatic/extrapancreatic complications. Unfortunately, CP pain continues to be a major clinical challenge. It is recognized that ongoing pain may induce altered central pain processing, e.g., central sensitization or pro-nociceptive pain modulation. When this is present conventional pain treatment targeting the nociceptive focus, e.g., opioid analgesia or surgical/endoscopic intervention, often fails even if technically successful. If central nervous system pain processing is altered, specific treatment targeting these changes should be instituted (e.g., gabapentinoids, ketamine or tricyclic antidepressants). Suitable tools are now available to make altered central processing visible, including quantitative sensory testing, electroencephalograpy and (functional) magnetic resonance imaging. These techniques are potentially clinically useful diagnostic tools to analyze central pain processing and thus define optimum management approaches for pain in CP and other visceral pain syndromes. The present review proposes a systematic mechanism-orientated approach to pain management in CP based on a holistic view of the mechanisms involved. Future research should address the circumstances under which central nervous system pain processing changes in CP, and how this is influenced by ongoing nociceptive input and therapies. Thus we hope to predict which patients are at risk for developing chronic pain or not responding to therapy, leading to improved treatment of chronic pain in CP and other visceral pain disorders.", "author" : [ { "dropping-particle" : "", "family" : "Bouwense", "given" : "Stefan A W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vries", "given" : "Marjan", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schreuder", "given" : "Luuk T W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olesen", "given" : "S\u00f8ren S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fr\u00f8kj\u00e6r", "given" : "Jens B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goor", "given" : "Harry", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "Oliver H G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "World journal of gastroenterology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2015", "1", "7" ] ] }, "page" : "47-59", "title" : "Systematic mechanism-orientated approach to chronic pancreatitis pain.", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(103)", "plainTextFormattedCitation" : "(103)", "previouslyFormattedCitation" : "(103)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(103). In summary, surgery has to be tailored to the needs of patients and should be problem-oriented and preferably organ-sparing, and performed after thorough evaluation in an interdisciplinary setting in a high-volume center with expertise in pancreatic surgery. The success of surgery (or other invasive treatments) depends on the cause of pain and the nervous sytem status of processes painful stimuli (e.g. peripheral and central sensitization)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3748/wjg.v21.i1.47", "ISSN" : "2219-2840", "PMID" : "25574079", "abstract" : "Pain in chronic pancreatitis (CP) shows similarities with other visceral pain syndromes (i.e., inflammatory bowel disease and esophagitis), which should thus be managed in a similar fashion. Typical causes of CP pain include increased intrapancreatic pressure, pancreatic inflammation and pancreatic/extrapancreatic complications. Unfortunately, CP pain continues to be a major clinical challenge. It is recognized that ongoing pain may induce altered central pain processing, e.g., central sensitization or pro-nociceptive pain modulation. When this is present conventional pain treatment targeting the nociceptive focus, e.g., opioid analgesia or surgical/endoscopic intervention, often fails even if technically successful. If central nervous system pain processing is altered, specific treatment targeting these changes should be instituted (e.g., gabapentinoids, ketamine or tricyclic antidepressants). Suitable tools are now available to make altered central processing visible, including quantitative sensory testing, electroencephalograpy and (functional) magnetic resonance imaging. These techniques are potentially clinically useful diagnostic tools to analyze central pain processing and thus define optimum management approaches for pain in CP and other visceral pain syndromes. The present review proposes a systematic mechanism-orientated approach to pain management in CP based on a holistic view of the mechanisms involved. Future research should address the circumstances under which central nervous system pain processing changes in CP, and how this is influenced by ongoing nociceptive input and therapies. Thus we hope to predict which patients are at risk for developing chronic pain or not responding to therapy, leading to improved treatment of chronic pain in CP and other visceral pain disorders.", "author" : [ { "dropping-particle" : "", "family" : "Bouwense", "given" : "Stefan A W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vries", "given" : "Marjan", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schreuder", "given" : "Luuk T W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olesen", "given" : "S\u00f8ren S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fr\u00f8kj\u00e6r", "given" : "Jens B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drewes", "given" : "Asbj\u00f8rn M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goor", "given" : "Harry", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "Oliver H G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "World journal of gastroenterology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2015", "1", "7" ] ] }, "page" : "47-59", "title" : "Systematic mechanism-orientated approach to chronic pancreatitis pain.", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1097/AAP.0b013e31822e0d4a", "ISSN" : "1532-8651", "PMID" : "22005656", "abstract" : "BACKGROUND AND OBJECTIVES Central sensitization due to visceral pancreatic nociceptive input may be important in chronic pancreatitis pain. We investigated whether bilateral thoracoscopic splanchnicectomy (BTS) to reduce nociceptive input in chronic pancreatitis patients (CPP) with poor pain control affects supraspinal and spinal sensitization. METHODS Seventeen CPP were studied preoperatively and 6 weeks after BTS. Pressure pain thresholds (PPT) were measured in clavicle and pancreatic dermatomes reflecting supraspinal and spinal central sensitization, respectively. Patients with increased PPT after BTS (hypoalgesic) were compared to those without (hyperalgesic) and PPT vs. pain numeric rating scale (NRS) changes compared. RESULTS After BTS, ten patients showed C5 PPT increases (hypoalgesic; median change 87 kPa), 7 patients had unaltered/lower PPT (hyperalgesic; -135 kPa). Preoperative pain NRS was similar between groups (4 vs. 5, P = 0.2). After BTS hypoalgesic group NRS was lower (1 vs. 6; P = 0.008) and NRS change greater (-2 vs. 0; P = 0.005). Whole group NRS and C5 PPT change correlated significantly and negatively (r = 0.53; P < 0.05), but not for pancreatic PPT. CONCLUSIONS Reduced supraspinal-but not spinal-central sensitization after BTS was associated with significantly reduced pain scores in a majority of CPP. A subgroup showed no reductions in supraspinal central sensitization after BTS, coupled to no significant pain NRS reduction. Our results suggest that a subgroup of CPP has altered pain processing that may be independent of ongoing peripheral nociceptive input, resulting in persisting pain despite BTS. If confirmed, these results indicate the importance of sensory testing for indications and management of pain treatments.", "author" : [ { "dropping-particle" : "", "family" : "Bouwense", "given" : "Stefan A W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buscher", "given" : "Hessel C J L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goor", "given" : "Harry", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "Oliver H G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Regional anesthesia and pain medicine", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2011", "11" ] ] }, "note" : "NULL", "page" : "531-6", "title" : "Has central sensitization become independent of nociceptive input in chronic pancreatitis patients who fail thoracoscopic splanchnicectomy?", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.pan.2012.12.078", "ISSN" : "14243903", "author" : [ { "dropping-particle" : "", "family" : "Bouwense", "given" : "S.A.W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ali", "given" : "U.A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Broek", "given" : "R.P.G.", "non-dropping-particle" : "ten", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Issa", "given" : "Y.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eijck", "given" : "C.H.", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gooszen", "given" : "H.G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "O.H.G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goor", "given" : "H.", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreatology", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2013", "3" ] ] }, "page" : "e7", "publisher" : "Elsevier", "title" : "Pain outcome after pancreatic surgery for pain of chronic pancreatitis: Relation to altered central pain processing", "type" : "article-journal", "volume" : "13" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(103,285,335)", "plainTextFormattedCitation" : "(103,285,335)", "previouslyFormattedCitation" : "(103,285,335)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(103,285,335).PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Cb3V3ZW5zZTwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+

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ADDIN EN.CITE.DATA In this context, the pain processing status needs to be taken into account decising for surgery and the indication of surgery should be considered early once symptoms are unambiguous and opioids are needed. With regards to the surgical method, the duodenum-preserving pancreatic head resections (including Beger, Frey, and Berne procedures) have been shown to be superior to the classic Whipple procedure, while Frey, Beger and Berne procedures have similar results when being compared to each other. Thus, the choice of procedure should be determined by other factors, such as the presence of secondary complications of pancreatitis, intra-operative findings and individual experience of the surgeonADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.hpb.2015.10.003", "ISSN" : "1477-2574", "PMID" : "26902130", "abstract" : "BACKGROUND To evaluate the short and long term outcomes of duodenum preserving pancreatic head resection (DPPHR) procedures in the treatment of painful chronic pancreatitis. METHODS A systematic literature search was performed to identify all comparative studies evaluating long and short term postoperative outcomes (pain relief, morbidity and mortality, pancreatic exocrine and endocrine function). RESULTS Five published studies fulfilled the inclusion criteria including 1 randomized controlled trial comparing the Beger and Frey procedure. In total, 323 patients underwent surgical procedures for chronic pancreatitis, including Beger (n = 138) and Frey (n = 99), minimal Frey (n = 32), modified Frey (n = 25) and Berne's modification (n = 29). Two studies comparing the Beger and Frey procedure were entered into a meta-analysis and showed no difference in post-operative pain (RD = -0.06; CI -0.21 to 0.09), mortality (RD = 0.01; CI -0.03 to 0.05), morbidity (RD = 0.12; CI -0.00 to 0.24), exocrine insufficiency (RD = 0.04; CI -0.10 to 0.18) and endocrine insufficiency (RD = -0.14 CI -0.28 to 0.01). CONCLUSION All procedures are equally effective for the management of pain for chronic pancreatitis. The choice of procedure should be determined by other factors including the presence of secondary complications of pancreatitis and intra-operative findings. Registration number CRD42015019275. Centre for Reviews and Dissemination, University of York, 2009.", "author" : [ { "dropping-particle" : "", "family" : "Jawad", "given" : "Zaynab A R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsim", "given" : "Nicole", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pai", "given" : "Madhava", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bansi", "given" : "Dev", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Westaby", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vlavianos", "given" : "Panagiotis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jiao", "given" : "Long R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "HPB : the official journal of the International Hepato Pancreato Biliary Association", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2016", "2" ] ] }, "note" : "NULL", "page" : "121-8", "title" : "Short and long-term post-operative outcomes of duodenum preserving pancreatic head resection for chronic pancreatitis affecting the head of pancreas: a systematic review and meta-analysis.", "type" : "article-journal", "volume" : "18" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(336)", "plainTextFormattedCitation" : "(336)", "previouslyFormattedCitation" : "(336)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(336). Ihsan Ekin Demir and Güralp O CeyhanQ11. When is the optimal time for surgery in painful CP?Current evidence on the timing of surgery for painful CP suggests a beneficial role for early surgery, i.e. 1) within the first 2 to 3 years after diagnosis or symptom onset, 2) for patients who had equal to or fewer than 5 endoscopic procedures, and 3) for patients who have not yet required opioid analgesics for medical pain treatment (Quality assessment: low; Recommendation: weak; Agreement: strong).Pain, when refractory to medical treatment, represents one of the leading indications for surgery on patients with chronic pancreatitis (CP). Depending on the morphology of the pancreatic duct and the extent of inflammatory alterations in the pancreatic head, pancreatic drainage or resection procedures can be performed. For either type of surgery, high rates of postoperative pain relief of around 60-90% has been reported in numerous studiesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s11605-007-0155-6", "ISSN" : "1091-255X", "PMID" : "17534689", "abstract" : "INTRODUCTION Organ complications like biliary or duodenal stenosis as well as intractable pain are current indications for surgery in patients with chronic pancreatitis (CP). We present here our experience with pancreatic resection for CP and focus on the long-term outcome after surgery regarding pain, exocrine/endocrine pancreatic function, and the control of organ complications in 224 patients with a median postoperative follow-up period of 56 months. METHODS During 11 years 272 pancreatic resections were performed in our institution for CP. Perioperative mortality was 1%. Follow-up data using at least standardized questionnaires were available in 224 patients. The types of resection in these 224 patients were Whipple (9%), pylorus-preserving pancreato-duodenectomy (PD) (PPPD; 40%), duodenum-preserving pancreatic head resection (DPPHR; 41%, 50 Frey, 42 Beger), distal (9%) and two central pancreatic resections. Eighty-six of the patients were part of a randomized study comparing PPPD and DPPHR. The perioperative and follow-up (f/up) data were prospectively documented. Exocrine insufficiency was regarded as the presence of steatorrhea and/or the need for oral enzyme supplementation. Multivariate analysis was performed using binary logistic regression. RESULTS Perioperative surgical morbidity was 28% and did not differ between the types of resection. At last f/up 87% of the patients were pain-free (60%) or had pain less frequently than once per week (27%). Thirteen percent had frequent pain, at least once per week (no difference between the operative procedures). A concomitant exocrine insufficiency and former postoperative surgical complications were the strongest independent risk factors for pain and frequent pain at follow-up. At the last f/up 65% had exocrine insufficiency, half of them developed it during the postoperative course. The presence of regional or generalized portal hypertension, a low preoperative body mass index, and a longer preoperative duration of CP were independent risk factors for exocrine insufficiency. Thirty-seven percent of the patients without preoperative diabetes developed de novo diabetes during f/up (no risk factor identified). Both, exocrine and endocrine insufficiencies were independent of the type of surgery. Median weight gain was 2 kg and higher in patients with preoperative malnutrition and in patients without abdominal pain. After PPPD, 8% of the patients had peptic jejunal ulcers, whereas 4% presented with biliary\u2026", "author" : [ { "dropping-particle" : "", "family" : "Riediger", "given" : "Hartwig", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adam", "given" : "Ulrich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fischer", "given" : "Eva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keck", "given" : "Tobias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pfeffer", "given" : "Frank", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hopt", "given" : "Ulrich T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Makowiec", "given" : "Frank", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2007", "8", "10" ] ] }, "note" : "NULL", "page" : "949-59; discussion 959-60", "title" : "Long-term outcome after resection for chronic pancreatitis in 224 patients.", "type" : "article-journal", "volume" : "11" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.amjsurg.2007.08.065", "ISSN" : "1879-1883", "PMID" : "18513691", "abstract" : "BACKGROUND Many patients require surgery for chronic pancreatitis (CP). By combining the essences of the Beger and the Frey procedures, a hybrid procedure was developed: central pancreatic-head resection (CPHR) (Berne technique). METHODS A prospective evaluation of 100 consecutive patients who underwent CPHR for CP between January 2002 and December 2006 was performed. Long-term follow-up, including quality-of-life (QOL) assessment, was carried out. RESULTS The hospital mortality rate was 1%; the surgical morbidity rate was 16%; and the relaparotomy rate was 6%. Mean surgery time was 295 +/- 7 minutes; mean intraoperative blood loss was 763 +/- 75 mL; and the mean postsurgical hospital stay was 11.4 +/- .8 days. After a median follow-up of 41 months, pain was improved in 55% of patients; weight increase occurred in 67% of patients; and insulin-dependent diabetes mellitus developed in 22% of the patients. Comparison of QOL parameters with a German adult control population showed no statistically significant differences. CONCLUSIONS CPHR is a safe surgical option to resolve CP-associated problems. Long-term follow-up QOL after CPHR shows results comparable with date published data after the Beger and the Frey procedures.", "author" : [ { "dropping-particle" : "", "family" : "M\u00fcller", "given" : "Michael W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Friess", "given" : "Helmut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leitzbach", "given" : "Sarah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Michalski", "given" : "Christoph W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berberat", "given" : "Pascal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ceyhan", "given" : "G\u00fcralp O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hinz", "given" : "Ulf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ho", "given" : "Choon-Kiat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "K\u00f6ninger", "given" : "J\u00f6rg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kleeff", "given" : "J\u00f6rg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "B\u00fcchler", "given" : "Markus W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American journal of surgery", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2008", "9" ] ] }, "note" : "NULL", "page" : "364-72", "title" : "Perioperative and follow-up results after central pancreatic head resection (Berne technique) in a consecutive series of patients with chronic pancreatitis.", "type" : "article-journal", "volume" : "196" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1007/s11605-009-1119-9", "ISSN" : "1873-4626", "PMID" : "20033344", "abstract" : "INTRODUCTION Duodenum-preserving pancreatic head resection may be an alternative to pancreatoduodenectomy or drainage procedures for chronic pancreatitis. There are few studies directly comparing the long-term outcome after the operations described by Beger and Frey. METHODS One hundred thirteen patients underwent duodenum-preserving pancreatic head resection for complications of chronic pancreatitis. Follow-up was obtained in 92 patients (42 Beger, 50 Frey, median follow-up almost 5 years). RESULTS Overall/surgery-related perioperative morbidity was 30%/20% (Frey) and 40%/31% (Beger). In long-term follow-up (Frey vs Beger), 62% vs 50% were completely free of pain, but 6% vs 19% had pain at least once per week or daily, and 32% vs 31% experienced pain attacks at least once per year (n.s.). Diabetes mellitus occurred in 60% vs 57% (de novo 34% vs 17%). Rates of exocrine insufficiency were 76% vs. 74% (de novo 34% vs. 33%). Median gain in body weight was 2.5 vs 1.5 kg (n.s.), respectively. Four patients had clinically relevant biliary complications during follow-up requiring reintervention. CONCLUSIONS Our (nonrandomized) comparison of the long-term outcome after Frey and Beger procedures for chronic pancreatitis reveals a tendency for better pain control with the Frey operation. The functional outcomes were almost identical.", "author" : [ { "dropping-particle" : "", "family" : "Keck", "given" : "Tobias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wellner", "given" : "Ulrich Friedrich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Riediger", "given" : "Hartwig", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adam", "given" : "Ulrich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sick", "given" : "Olivia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hopt", "given" : "Ulrich Theodor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Makowiec", "given" : "Frank", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract", "id" : "ITEM-3", "issue" : "3", "issued" : { "date-parts" : [ [ "2010", "3", "22" ] ] }, "note" : "NULL", "page" : "549-56", "title" : "Long-term outcome after 92 duodenum-preserving pancreatic head resections for chronic pancreatitis: comparison of Beger and Frey procedures.", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(337\u2013339)", "plainTextFormattedCitation" : "(337\u2013339)", "previouslyFormattedCitation" : "(337\u2013339)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(337–339), including randomized controlled trials (RCTs)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1056/NEJMoa060610", "ISSN" : "0028-4793", "PMID" : "17301298", "abstract" : "BACKGROUND For patients with chronic pancreatitis and a dilated pancreatic duct, ductal decompression is recommended. We conducted a randomized trial to compare endoscopic and surgical drainage of the pancreatic duct. METHODS All symptomatic patients with chronic pancreatitis and a distal obstruction of the pancreatic duct but without an inflammatory mass were eligible for the study. We randomly assigned patients to undergo endoscopic transampullary drainage of the pancreatic duct or operative pancreaticojejunostomy. The primary end point was the average Izbicki pain score during 2 years of follow-up. The secondary end points were pain relief at the end of follow-up, physical and mental health, morbidity, mortality, length of hospital stay, number of procedures undergone, and changes in pancreatic function. RESULTS Thirty-nine patients underwent randomization: 19 to endoscopic treatment (16 of whom underwent lithotripsy) and 20 to operative pancreaticojejunostomy. During the 24 months of follow-up, patients who underwent surgery, as compared with those who were treated endoscopically, had lower Izbicki pain scores (25 vs. 51, P<0.001) and better physical health summary scores on the Medical Outcomes Study 36-Item Short-Form General Health Survey questionnaire (P=0.003). At the end of follow-up, complete or partial pain relief was achieved in 32% of patients assigned to endoscopic drainage as compared with 75% of patients assigned to surgical drainage (P=0.007). Rates of complications, length of hospital stay, and changes in pancreatic function were similar in the two treatment groups, but patients receiving endoscopic treatment required more procedures than did patients in the surgery group (a median of eight vs. three, P<0.001). CONCLUSIONS Surgical drainage of the pancreatic duct was more effective than endoscopic treatment in patients with obstruction of the pancreatic duct due to chronic pancreatitis. (Current Controlled Trials number, ISRCTN04572410 [controlled-].).", "author" : [ { "dropping-particle" : "", "family" : "Cahen", "given" : "Djuna L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gouma", "given" : "Dirk J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nio", "given" : "Yung", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rauws", "given" : "Erik A. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boermeester", "given" : "Marja A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Busch", "given" : "Olivier R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stoker", "given" : "Jaap", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lam\u00e9ris", "given" : "Johan S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dijkgraaf", "given" : "Marcel G.W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huibregtse", "given" : "Kees", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruno", "given" : "Marco J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "New England Journal of Medicine", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2007", "2", "15" ] ] }, "page" : "676-684", "title" : "Endoscopic versus Surgical Drainage of the Pancreatic Duct in Chronic Pancreatitis", "type" : "article-journal", "volume" : "356" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(232)", "plainTextFormattedCitation" : "(232)", "previouslyFormattedCitation" : "(232)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(232). Despite this effectiveness of surgery in the treatment of CP-associated pain, the time when a patient is referred to surgery, and the time point when a medical treatment is assumed to have “failed”, varies extensively between centers. Due its technical complexity and its perceived potential mortality/morbidity, pancreatic surgery does still not find frequent use for patients with a long-history of CP-associated pain. However, in the largest series, the overall mortality and morbidity after surgery for CP has been reported to lie only around 1% and 20-30%, respectivelyADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.amjsurg.2007.08.065", "ISSN" : "1879-1883", "PMID" : "18513691", "abstract" : "BACKGROUND Many patients require surgery for chronic pancreatitis (CP). By combining the essences of the Beger and the Frey procedures, a hybrid procedure was developed: central pancreatic-head resection (CPHR) (Berne technique). METHODS A prospective evaluation of 100 consecutive patients who underwent CPHR for CP between January 2002 and December 2006 was performed. Long-term follow-up, including quality-of-life (QOL) assessment, was carried out. RESULTS The hospital mortality rate was 1%; the surgical morbidity rate was 16%; and the relaparotomy rate was 6%. Mean surgery time was 295 +/- 7 minutes; mean intraoperative blood loss was 763 +/- 75 mL; and the mean postsurgical hospital stay was 11.4 +/- .8 days. After a median follow-up of 41 months, pain was improved in 55% of patients; weight increase occurred in 67% of patients; and insulin-dependent diabetes mellitus developed in 22% of the patients. Comparison of QOL parameters with a German adult control population showed no statistically significant differences. CONCLUSIONS CPHR is a safe surgical option to resolve CP-associated problems. Long-term follow-up QOL after CPHR shows results comparable with date published data after the Beger and the Frey procedures.", "author" : [ { "dropping-particle" : "", "family" : "M\u00fcller", "given" : "Michael W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Friess", "given" : "Helmut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leitzbach", "given" : "Sarah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Michalski", "given" : "Christoph W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berberat", "given" : "Pascal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ceyhan", "given" : "G\u00fcralp O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hinz", "given" : "Ulf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ho", "given" : "Choon-Kiat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "K\u00f6ninger", "given" : "J\u00f6rg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kleeff", "given" : "J\u00f6rg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "B\u00fcchler", "given" : "Markus W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American journal of surgery", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2008", "9" ] ] }, "note" : "NULL", "page" : "364-72", "title" : "Perioperative and follow-up results after central pancreatic head resection (Berne technique) in a consecutive series of patients with chronic pancreatitis.", "type" : "article-journal", "volume" : "196" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(338)", "plainTextFormattedCitation" : "(338)", "previouslyFormattedCitation" : "(338)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(338). Despite these acceptable figures, CP patients with severe pain requiring opioid analgesics are rarely referred to surgery in the first years after diagnosis. Rather, endoscopic measures are applied, yet evidence for the effectiveness of endoscopic interventions in the early phase of CP with regard to short or long-term pain relief, is, when compared to surgery, weakerADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.bpg.2010.03.002", "ISSN" : "1532-1916", "PMID" : "20510829", "abstract" : "Endoscopic treatment of chronic pancreatitis (CP) aims to relieve pain by draining the main pancreatic duct (MPD) and to treat loco-regional complications. Half of patients have complete pain relief five years after treatment, with best results obtained if treatment is performed early after the first pain attack. If MPD obstruction is caused by calcifications, ambulatory extracorporeal shock wave lithotripsy has become a first-line treatment (9-30% of patients require ERCP during follow-up). If MPD obstruction is caused by stricture(s), insertion of single plastic stent is effective but it requires multiple ERCPs for stent exchanges; other protocols are being investigated. Pseudocysts represent an excellent indication for endoscopic treatment with long-term results similar to those of surgery; endosonography-guided techniques allow treatment of almost any pancreatic pseudocyst. Biliary strictures related to CP are challenging due to a high relapse rate and requirement for multiple ERCP sessions. Significant progress has recently been made with new protocols of temporary biliary stenting (multiple simultaneous plastic stents or covered metallic stents).", "author" : [ { "dropping-particle" : "", "family" : "Nguyen-Tang", "given" : "Thai", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dumonceau", "given" : "Jean-Marc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Best practice & research. Clinical gastroenterology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2010", "6" ] ] }, "note" : "NULL", "page" : "281-98", "title" : "Endoscopic treatment in chronic pancreatitis, timing, duration and type of intervention.", "type" : "article-journal", "volume" : "24" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(340)", "plainTextFormattedCitation" : "(340)", "previouslyFormattedCitation" : "(340)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(340), for detailed information see the endoscopy section.Currently, although there are no prospective controlled studies that specifically addressed the timing of surgery for painful CP, increasing amount of evidence suggests that surgery should be considered early for better pain outcomes. In a systematic review that analyzed the role of timing, Yang et al. found that the definition of “early” versus “late” was variable between eligible studiesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s11605-014-2571-8", "ISSN" : "1873-4626", "PMID" : "24944153", "abstract" : "BACKGROUND Surgical intervention has traditionally been reserved as the last management option for pain in chronic pancreatitis. Recently, there has been a call for surgery to be offered earlier in the disease process. The objectives of this review were to evaluate the effect of early surgery on postoperative pain, pancreatic function, and re-intervention rates in chronic pancreatitis. METHODS A systematic literature search through EMBASE, Cochrane Review, and PubMed from January 1950 to January 2014 was conducted. Citations found in relevant papers are hand-searched. Data which could be pooled were analyzed using Revman (v5.2). Risk of bias analysis was conducted. RESULTS Of the 2,886 potentially eligible studies identified, 11 studies met the inclusion criteria. There was large heterogeneity in the study designs, and studies were conducted over a lengthy time span. Seven studies examined pain, three studies examined pancreatic function, and three studies examined rates of re-intervention. Meta-analysis of the three studies with comparative raw data regarding complete pain relief showed that early surgery was associated with an increased likelihood of complete postoperative pain relief (RR\u2009=\u20091.67, 95% CI 1.09-2.56, p\u2009=\u20090.02). Early surgery was also associated with reduced risk of pancreatic insufficiency and low re-intervention rates. CONCLUSIONS Data from this study supports considering early surgery for pain management in patients with chronic pancreatitis, with the potential of a reduced risk of pancreatic insufficiency and the need for further intervention. Further prospective randomized studies are warranted comparing early surgery against conservative step-up approaches.", "author" : [ { "dropping-particle" : "", "family" : "Yang", "given" : "Catherine J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bliss", "given" : "Lindsay A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schapira", "given" : "Emily F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freedman", "given" : "Steven D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Sing Chau", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Windsor", "given" : "John A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tseng", "given" : "Jennifer F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2014", "10", "19" ] ] }, "note" : "NULL", "page" : "1863-9", "title" : "Systematic review of early surgery for chronic pancreatitis: impact on pain, pancreatic function, and re-intervention.", "type" : "article-journal", "volume" : "18" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(323)", "plainTextFormattedCitation" : "(323)", "previouslyFormattedCitation" : "(323)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(323). Still, the concordant finding from 11 studies was that early surgery was associated with a greater probability to attain postoperative pain relief (RR=1.67, 95% CI: 1.09-2.56, p=0.02)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s11605-014-2571-8", "ISSN" : "1873-4626", "PMID" : "24944153", "abstract" : "BACKGROUND Surgical intervention has traditionally been reserved as the last management option for pain in chronic pancreatitis. Recently, there has been a call for surgery to be offered earlier in the disease process. The objectives of this review were to evaluate the effect of early surgery on postoperative pain, pancreatic function, and re-intervention rates in chronic pancreatitis. METHODS A systematic literature search through EMBASE, Cochrane Review, and PubMed from January 1950 to January 2014 was conducted. Citations found in relevant papers are hand-searched. Data which could be pooled were analyzed using Revman (v5.2). Risk of bias analysis was conducted. RESULTS Of the 2,886 potentially eligible studies identified, 11 studies met the inclusion criteria. There was large heterogeneity in the study designs, and studies were conducted over a lengthy time span. Seven studies examined pain, three studies examined pancreatic function, and three studies examined rates of re-intervention. Meta-analysis of the three studies with comparative raw data regarding complete pain relief showed that early surgery was associated with an increased likelihood of complete postoperative pain relief (RR\u2009=\u20091.67, 95% CI 1.09-2.56, p\u2009=\u20090.02). Early surgery was also associated with reduced risk of pancreatic insufficiency and low re-intervention rates. CONCLUSIONS Data from this study supports considering early surgery for pain management in patients with chronic pancreatitis, with the potential of a reduced risk of pancreatic insufficiency and the need for further intervention. Further prospective randomized studies are warranted comparing early surgery against conservative step-up approaches.", "author" : [ { "dropping-particle" : "", "family" : "Yang", "given" : "Catherine J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bliss", "given" : "Lindsay A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schapira", "given" : "Emily F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freedman", "given" : "Steven D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Sing Chau", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Windsor", "given" : "John A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tseng", "given" : "Jennifer F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2014", "10", "19" ] ] }, "note" : "NULL", "page" : "1863-9", "title" : "Systematic review of early surgery for chronic pancreatitis: impact on pain, pancreatic function, and re-intervention.", "type" : "article-journal", "volume" : "18" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(323)", "plainTextFormattedCitation" : "(323)", "previouslyFormattedCitation" : "(323)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(323). Moreover, in the meta-analysis of two studies, early surgery was associated with an increased likelihood of “complete” postoperative pain relief. In these two studies, early surgery was performed within the first 21 months after symptom onset ADDIN EN.CITE <EndNote><Cite><Author>Cahen</Author><Year>2007</Year><RecNum>261</RecNum><record><rec-number>261</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Cahen, D. L.</author><author>Gouma, D. J.</author><author>Nio, Y.</author><author>Rauws, E. A.</author><author>Boermeester, M. A.</author><author>Busch, O. R.</author><author>Stoker, J.</author><author>Lameris, J. S.</author><author>Dijkgraaf, M. G.</author><author>Huibregtse, K.</author><author>Bruno, M. J.</author></authors></contributors><auth-address>Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands. djca@zha.nl</auth-address><titles><title>Endoscopic versus surgical drainage of the pancreatic duct in chronic pancreatitis</title><secondary-title>N Engl J Med</secondary-title></titles><periodical><full-title>N Engl J Med</full-title></periodical><pages>676-84</pages><volume>356</volume><number>7</number><keywords><keyword>Adult</keyword><keyword>Calculi/surgery/therapy</keyword><keyword>Cholangiopancreatography, Endoscopic Retrograde</keyword><keyword>Constriction, Pathologic/therapy</keyword><keyword>*Drainage</keyword><keyword>Female</keyword><keyword>Follow-Up Studies</keyword><keyword>Humans</keyword><keyword>Lithotripsy</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Pain/etiology</keyword><keyword>Pain Management</keyword><keyword>Pancreatic Ducts/*surgery</keyword><keyword>Pancreaticojejunostomy</keyword><keyword>Pancreatitis, Chronic/surgery/*therapy</keyword><keyword>*Sphincterotomy, Endoscopic</keyword><keyword>Stents</keyword></keywords><dates><year>2007</year><pub-dates><date>Feb 15</date></pub-dates></dates><accession-num>17301298</accession-num><urls><related-urls><url> </url></related-urls></urls></record></Cite></EndNote>(Cahen et al., 2007), or within 5 years of clinical diseaseADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1055/s-2003-40237", "ISSN" : "0013-726X", "PMID" : "12822088", "abstract" : "BACKGROUND AND STUDY AIMS Invasive treatment for abdominal pain due to chronic pancreatitis may be either surgical or endoscopic, particularly in cases of ductal obstruction. To date, the data published on the effectiveness of these two forms of therapy have been mostly retrospective, and there have been no randomized studies. A prospective, randomized study comparing surgery with endoscopy in patients with painful obstructive chronic pancreatitis was therefore conducted. PATIENTS AND METHODS Consecutive patients with pancreatic duct obstruction and pain were invited to participate in a randomized trial comparing endotherapy and surgery, the latter consisting of resection and drainage procedures, depending on the patient's individual situation. Patients who did not agree to participation and randomization were also further assessed using the same follow-up protocol. RESULTS Of 140 eligible patients, only 72 agreed to be randomized. Surgery consisted of resection (80 %) and drainage (20 %) procedures, while endotherapy included sphincterotomy and stenting (52 %) and/or stone removal (23 %). In the entire group, the initial success rates were similar for both groups, but at the 5-year follow-up, complete absence of pain was more frequent after surgery (37 % vs. 14 %), with the rate of partial relief being similar (49 % vs. 51 %). In the randomized subgroup, results were similar (pain absence 34 % after surgery vs. 15 % after endotherapy, relief 52 % after surgery vs. 46 % after endotherapy). The increase in body weight was also greater by 20 - 25 % in the surgical group, while new-onset diabetes developed with similar frequency in both groups (34 - 43 %), again with no differences between the results for the whole group and the randomized subgroup. CONCLUSIONS Surgery is superior to endotherapy for long-term pain reduction in patients with painful obstructive chronic pancreatitis. Better selection of patients for endotherapy may be helpful in order to maximize results. Due to its low degree of invasiveness, however, endotherapy can be offered as a first-line treatment, with surgery being performed in case of failure and/or recurrence.", "author" : [ { "dropping-particle" : "", "family" : "D\u00edte", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruzicka", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zboril", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Novotn\u00fd", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Endoscopy", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2003", "7" ] ] }, "note" : "NULL", "page" : "553-558", "title" : "A Prospective, Randomized Trial Comparing Endoscopic and Surgical Therapy for Chronic Pancreatitis", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(233)", "plainTextFormattedCitation" : "(233)", "previouslyFormattedCitation" : "(233)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(233). In a retrospective series, preoperative duration of CP for greater than 3 years tended to results in higher postoperative pain persistence rates (43% vs. 37%)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s11605-007-0155-6", "ISSN" : "1091-255X", "PMID" : "17534689", "abstract" : "INTRODUCTION Organ complications like biliary or duodenal stenosis as well as intractable pain are current indications for surgery in patients with chronic pancreatitis (CP). We present here our experience with pancreatic resection for CP and focus on the long-term outcome after surgery regarding pain, exocrine/endocrine pancreatic function, and the control of organ complications in 224 patients with a median postoperative follow-up period of 56 months. METHODS During 11 years 272 pancreatic resections were performed in our institution for CP. Perioperative mortality was 1%. Follow-up data using at least standardized questionnaires were available in 224 patients. The types of resection in these 224 patients were Whipple (9%), pylorus-preserving pancreato-duodenectomy (PD) (PPPD; 40%), duodenum-preserving pancreatic head resection (DPPHR; 41%, 50 Frey, 42 Beger), distal (9%) and two central pancreatic resections. Eighty-six of the patients were part of a randomized study comparing PPPD and DPPHR. The perioperative and follow-up (f/up) data were prospectively documented. Exocrine insufficiency was regarded as the presence of steatorrhea and/or the need for oral enzyme supplementation. Multivariate analysis was performed using binary logistic regression. RESULTS Perioperative surgical morbidity was 28% and did not differ between the types of resection. At last f/up 87% of the patients were pain-free (60%) or had pain less frequently than once per week (27%). Thirteen percent had frequent pain, at least once per week (no difference between the operative procedures). A concomitant exocrine insufficiency and former postoperative surgical complications were the strongest independent risk factors for pain and frequent pain at follow-up. At the last f/up 65% had exocrine insufficiency, half of them developed it during the postoperative course. The presence of regional or generalized portal hypertension, a low preoperative body mass index, and a longer preoperative duration of CP were independent risk factors for exocrine insufficiency. Thirty-seven percent of the patients without preoperative diabetes developed de novo diabetes during f/up (no risk factor identified). Both, exocrine and endocrine insufficiencies were independent of the type of surgery. Median weight gain was 2 kg and higher in patients with preoperative malnutrition and in patients without abdominal pain. After PPPD, 8% of the patients had peptic jejunal ulcers, whereas 4% presented with biliary\u2026", "author" : [ { "dropping-particle" : "", "family" : "Riediger", "given" : "Hartwig", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adam", "given" : "Ulrich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fischer", "given" : "Eva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keck", "given" : "Tobias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pfeffer", "given" : "Frank", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hopt", "given" : "Ulrich T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Makowiec", "given" : "Frank", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2007", "8", "10" ] ] }, "note" : "NULL", "page" : "949-59; discussion 959-60", "title" : "Long-term outcome after resection for chronic pancreatitis in 224 patients.", "type" : "article-journal", "volume" : "11" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(337)", "plainTextFormattedCitation" : "(337)", "previouslyFormattedCitation" : "(337)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(337). Clarke et al. reported somewhat better rates of pain relief after surgery for CP within 54 months versus for 87 months after diagnosisADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.cgh.2011.12.040", "ISSN" : "1542-7714", "PMID" : "22245964", "abstract" : "BACKGROUND & AIMS Endoscopic therapy (ET) frequently is used to treat patients with painful chronic pancreatitis (CP), but little is known about outcomes of patients for whom ET was not successful who then underwent surgery, or outcomes after ET compared with only medical treatment. We evaluated use and long-term effectiveness of ET in a well-defined cohort of patients with CP. METHODS We analyzed data from 146 patients with CP who participated in the North American Pancreatitis Study 2 at the University of Pittsburgh Medical Center from 2000 to 2006; 71 (49%) patients received ET at the University of Pittsburgh Medical Center. Success of ET and surgery were defined by cessation of narcotic therapy and resolution of episodes of acute pancreatitis. Disease progression was followed up from its onset until January 1, 2011 (mean, 8.2 \u00b1 4.7 y). RESULTS Patients who underwent ET had more symptoms (pain, recurrent pancreatitis) and had more complex pancreatic morphology (based on imaging) than patients who received medical therapy. ET had a high rate of technical success (60 of 71 cases; 85%); its rates of clinical success were 51% for 28 of 55 patients for whom follow-up data were available (mean time, 4.8 \u00b1 3.0 y) and 50% for 12 of 24 patients who underwent surgery after receiving ET. Patients who responded to ET were significantly older, had a shorter duration of disease before ET, had less constant pain, and required fewer daily narcotics than patients who did not respond to ET. Among the 36 symptomatic patients who received medical therapy and were followed up for a mean period of 5.7 \u00b1 4.1 years, 31% improved and 53% had no change in symptoms; of these, 21% underwent surgery. CONCLUSIONS ET is clinically successful for 50% of patients with symptomatic CP. When ET is not successful, surgery has successful outcomes in 50% of patients. Symptoms resolve in 31% of symptomatic patients who receive only medical therapy.", "author" : [ { "dropping-particle" : "", "family" : "Clarke", "given" : "Bridger", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slivka", "given" : "Adam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tomizawa", "given" : "Yutaka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanders", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Papachristou", "given" : "Georgios I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Whitcomb", "given" : "David C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yadav", "given" : "Dhiraj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2012", "7" ] ] }, "note" : "NULL", "page" : "795-802", "title" : "Endoscopic therapy is effective for patients with chronic pancreatitis.", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(253)", "plainTextFormattedCitation" : "(253)", "previouslyFormattedCitation" : "(253)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(253). In a recent institutional retrospective study from the USA including 66 patients, Yang et al. calculated the optimal cutoff point for preoperative CP duration to reach best possible pain relief after surgery, and found 26.5 months or less after diagnosis to yield the best outcomeADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/MPA.0000000000000333", "ISSN" : "1536-4828", "PMID" : "25882695", "abstract" : "OBJECTIVES To examine if surgery performed for pain of chronic pancreatitis (CP) within 3 years diagnosis has greater odds of achieving complete pain relief than later surgery and to find optimal surgical timing for attaining pain relief in CP. METHODS Retrospective review of records at a tertiary institution 2003 to 2011 for CP where the operative indication was pain. Outcomes were pain-free status, opioid use, and pancreatic insufficiency at 3-year follow-up. Univariate analysis by Fisher exact tests. Receiver operating curve to calculate cutoff threshold time for surgery. RESULTS Outcomes for 66 patients were included. Median preoperative CP duration was 28 months (interquartile range, 12, 67). Twenty-six patients (39.4%) were free of pain at the 3-year follow-up. Thirty-four patients (51.5%) were opioid users at follow-up. Postoperatively, 34 patients (51.5%) demonstrated endocrine, and 32 patients (48.5%) demonstrated exocrine insufficiency. The optimal cutoff point for preoperative CP duration was 26.5 months (area under the curve, 0.66). Shorter duration of CP before surgery was a predictor of pain-free status and reduced postoperative opioid use at follow-up. CONCLUSIONS Results from a single institution analysis suggest early surgical intervention of 26.5 months or less of diagnosis is associated with improved pain control, and optimal timing for surgery may be earlier than previously thought.", "author" : [ { "dropping-particle" : "", "family" : "Yang", "given" : "Catherine J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bliss", "given" : "Lindsay A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freedman", "given" : "Steven D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sheth", "given" : "Sunil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vollmer", "given" : "Charles M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Sing Chau", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Callery", "given" : "Mark P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tseng", "given" : "Jennifer F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreas", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2015", "7" ] ] }, "note" : "NULL", "page" : "819-23", "title" : "Surgery for chronic pancreatitis: the role of early surgery in pain management.", "type" : "article-journal", "volume" : "44" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(341)", "plainTextFormattedCitation" : "(341)", "previouslyFormattedCitation" : "(341)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(341). Furthermore, they identified shorter duration of CP before surgery as a predictor of pain-free status and reduced postoperative opioid useADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/MPA.0000000000000333", "ISSN" : "1536-4828", "PMID" : "25882695", "abstract" : "OBJECTIVES To examine if surgery performed for pain of chronic pancreatitis (CP) within 3 years diagnosis has greater odds of achieving complete pain relief than later surgery and to find optimal surgical timing for attaining pain relief in CP. METHODS Retrospective review of records at a tertiary institution 2003 to 2011 for CP where the operative indication was pain. Outcomes were pain-free status, opioid use, and pancreatic insufficiency at 3-year follow-up. Univariate analysis by Fisher exact tests. Receiver operating curve to calculate cutoff threshold time for surgery. RESULTS Outcomes for 66 patients were included. Median preoperative CP duration was 28 months (interquartile range, 12, 67). Twenty-six patients (39.4%) were free of pain at the 3-year follow-up. Thirty-four patients (51.5%) were opioid users at follow-up. Postoperatively, 34 patients (51.5%) demonstrated endocrine, and 32 patients (48.5%) demonstrated exocrine insufficiency. The optimal cutoff point for preoperative CP duration was 26.5 months (area under the curve, 0.66). Shorter duration of CP before surgery was a predictor of pain-free status and reduced postoperative opioid use at follow-up. CONCLUSIONS Results from a single institution analysis suggest early surgical intervention of 26.5 months or less of diagnosis is associated with improved pain control, and optimal timing for surgery may be earlier than previously thought.", "author" : [ { "dropping-particle" : "", "family" : "Yang", "given" : "Catherine J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bliss", "given" : "Lindsay A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freedman", "given" : "Steven D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sheth", "given" : "Sunil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vollmer", "given" : "Charles M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Sing Chau", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Callery", "given" : "Mark P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tseng", "given" : "Jennifer F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreas", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2015", "7" ] ] }, "note" : "NULL", "page" : "819-23", "title" : "Surgery for chronic pancreatitis: the role of early surgery in pain management.", "type" : "article-journal", "volume" : "44" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(341)", "plainTextFormattedCitation" : "(341)", "previouslyFormattedCitation" : "(341)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(341).Beyond the duration of CP, preoperative opioid use, or the frequency of endoscopic interventions also seems to influence the postoperative pain relief rates. Alexakis et al. analyzed the characteristics of 112 CP patients who underwent surgery, and found longer duration of pain and CP-associated symptoms among patients who were on opioids prior to surgeryADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.surg.2004.02.011", "ISSN" : "0039-6060", "PMID" : "15349108", "abstract" : "BACKGROUND The outcome of pancreatic resection for chronic pancreatitis in patients with preoperative opioid use is not well described. METHODS During 1997 to 2003, 112 of 231 patients referred with chronic pancreatitis underwent pancreatic resection. The outcome of patients who had preoperative opioid use (N=46) was compared with those without (N=66). RESULTS Patients who used opioids presented at a younger age and had a younger age of symptom onset, longer symptom duration, more hospitalizations, a higher frequency of diabetes mellitus, a higher pain score, and more restriction in daily activity (all P<.05). Twenty-one (46%) patients with opioid use had a total pancreatectomy compared with 9 (14%) without opioid use (P=.0002); the 21 patients also had a higher frequency of postoperative bleeding and early reoperation (8 vs 2, P<.02; 11 vs 3, P=.003, respectively). Mortality and overall morbidity was not significantly different between the 2 groups (4 vs 1, 27 vs 34, respectively). Pain scores improved postoperatively in both groups (P=.001) and was not significantly different between the groups from 12 months onward (median follow-up of 12 months, range, 3-60 months). Twenty percent of patients who used preoperative opioids however reverted to morphine use compared with 6% of patients who had not used opioids. CONCLUSIONS Patients who used opioids had more advanced disease than patients without opioid use, accounting for part of the postoperative morbidity. Although long-term pain relief was comparable between the 2 groups, maintaining opioid withdrawal was more problematic in those with preoperative opioid use. Earlier referral for resection may be warranted in this group of patients.", "author" : [ { "dropping-particle" : "", "family" : "Alexakis", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Connor", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghaneh", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raraty", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lombard", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smart", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Evans", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hughes", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Garvey", "given" : "C J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goulden", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parker", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sutton", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Neoptolemos", "given" : "J P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Surgery", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2004", "9" ] ] }, "note" : "NULL", "page" : "600-8", "title" : "Influence of opioid use on surgical and long-term outcome after resection for chronic pancreatitis.", "type" : "article-journal", "volume" : "136" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(342)", "plainTextFormattedCitation" : "(342)", "previouslyFormattedCitation" : "(342)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(342). During the first 24 months of follow-up, patients who had been on opioids preoperatively had greater pain scores after surgery than patients who had not previously used opioid analgesicsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.surg.2004.02.011", "ISSN" : "0039-6060", "PMID" : "15349108", "abstract" : "BACKGROUND The outcome of pancreatic resection for chronic pancreatitis in patients with preoperative opioid use is not well described. METHODS During 1997 to 2003, 112 of 231 patients referred with chronic pancreatitis underwent pancreatic resection. The outcome of patients who had preoperative opioid use (N=46) was compared with those without (N=66). RESULTS Patients who used opioids presented at a younger age and had a younger age of symptom onset, longer symptom duration, more hospitalizations, a higher frequency of diabetes mellitus, a higher pain score, and more restriction in daily activity (all P<.05). Twenty-one (46%) patients with opioid use had a total pancreatectomy compared with 9 (14%) without opioid use (P=.0002); the 21 patients also had a higher frequency of postoperative bleeding and early reoperation (8 vs 2, P<.02; 11 vs 3, P=.003, respectively). Mortality and overall morbidity was not significantly different between the 2 groups (4 vs 1, 27 vs 34, respectively). Pain scores improved postoperatively in both groups (P=.001) and was not significantly different between the groups from 12 months onward (median follow-up of 12 months, range, 3-60 months). Twenty percent of patients who used preoperative opioids however reverted to morphine use compared with 6% of patients who had not used opioids. CONCLUSIONS Patients who used opioids had more advanced disease than patients without opioid use, accounting for part of the postoperative morbidity. Although long-term pain relief was comparable between the 2 groups, maintaining opioid withdrawal was more problematic in those with preoperative opioid use. Earlier referral for resection may be warranted in this group of patients.", "author" : [ { "dropping-particle" : "", "family" : "Alexakis", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Connor", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghaneh", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raraty", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lombard", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smart", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Evans", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hughes", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Garvey", "given" : "C J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goulden", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parker", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sutton", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Neoptolemos", "given" : "J P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Surgery", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2004", "9" ] ] }, "note" : "NULL", "page" : "600-8", "title" : "Influence of opioid use on surgical and long-term outcome after resection for chronic pancreatitis.", "type" : "article-journal", "volume" : "136" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(342)", "plainTextFormattedCitation" : "(342)", "previouslyFormattedCitation" : "(342)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(342). A similar observation was made by Ahmed Ali et al. who evaluated 266 CP patients in a cohort study from five academic centers with a 5-year follow-upADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1001/archsurg.2012.1094", "ISSN" : "1538-3644", "PMID" : "23117832", "abstract" : "OBJECTIVE To evaluate the effect of timing of surgery on the long-term clinical outcome of surgery in chronic pancreatitis (CP). DESIGN Cohort study with long-term follow-up. SETTING Five specialized academic centers. PATIENTS Patients with CP treated surgically for pain. INTERVENTIONS Pancreatic resection and drainage procedures for pain relief. MAIN OUTCOME MEASURES Pain relief (pain visual analogue score \u22644), pancreatic function, and quality of life. RESULTS We included 266 patients with median follow-up of 62 months (interquartile range, 31-112). Results were presented as odds ratios (ORs)with 95% confidence intervals after correction for bias using bootstrap-corrected analysis. Pain relief was achieved in 149 patients (58%). Surgery within 3 years of symptoms was independently associated with more pain relief (OR, 1.8; 95% CI, 1.0-3.4; P = .03) and less endocrine pancreatic insufficiency (OR, 0.57; 95% CI, 0.33-0.96; P = .04). More pain relief was also observed in patients not taking opioids preoperatively (OR, 2.1; 95% CI, 1.2-4.0; P = .006) and who had 5 or fewer endoscopic treatments prior to surgery (OR, 2.5; 95% CI, 1.1-6.3; P = .04). The probability of achieving pain relief varied between 23% and 75%, depending on these risk factors. CONCLUSIONS The timing of surgery is an important risk factor for clinical outcome in CP. Surgery may need to be considered at an earlier phase than it is now, preferably within 3 years of symptomatic CP. Likelihood of postoperative pain relief can be calculated on an individual basis using the presented nomogram.", "author" : [ { "dropping-particle" : "", "family" : "Ahmed Ali", "given" : "Usama", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nieuwenhuijs", "given" : "Vincent B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eijck", "given" : "Casper H", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gooszen", "given" : "Hein G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dam", "given" : "Ronald M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Busch", "given" : "Olivier R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dijkgraaf", "given" : "Marcel G W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mauritz", "given" : "Femke A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jens", "given" : "Sjoerd", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mast", "given" : "Jay", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goor", "given" : "Harry", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boermeester", "given" : "Marja A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dutch Pancreatitis Study Group", "given" : "for the", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Archives of surgery (Chicago, Ill. : 1960)", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2012", "10", "1" ] ] }, "note" : "NULL", "page" : "925-32", "title" : "Clinical outcome in relation to timing of surgery in chronic pancreatitis: a nomogram to predict pain relief.", "type" : "article-journal", "volume" : "147" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(257)", "plainTextFormattedCitation" : "(257)", "previouslyFormattedCitation" : "(257)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(257). Here, they found that surgery within three years of pain onset was independently associated with more pain relief. Moreover, pain relief was more common among patients who were not taking opioids preoperativelyADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1001/archsurg.2012.1094", "ISSN" : "1538-3644", "PMID" : "23117832", "abstract" : "OBJECTIVE To evaluate the effect of timing of surgery on the long-term clinical outcome of surgery in chronic pancreatitis (CP). DESIGN Cohort study with long-term follow-up. SETTING Five specialized academic centers. PATIENTS Patients with CP treated surgically for pain. INTERVENTIONS Pancreatic resection and drainage procedures for pain relief. MAIN OUTCOME MEASURES Pain relief (pain visual analogue score \u22644), pancreatic function, and quality of life. RESULTS We included 266 patients with median follow-up of 62 months (interquartile range, 31-112). Results were presented as odds ratios (ORs)with 95% confidence intervals after correction for bias using bootstrap-corrected analysis. Pain relief was achieved in 149 patients (58%). Surgery within 3 years of symptoms was independently associated with more pain relief (OR, 1.8; 95% CI, 1.0-3.4; P = .03) and less endocrine pancreatic insufficiency (OR, 0.57; 95% CI, 0.33-0.96; P = .04). More pain relief was also observed in patients not taking opioids preoperatively (OR, 2.1; 95% CI, 1.2-4.0; P = .006) and who had 5 or fewer endoscopic treatments prior to surgery (OR, 2.5; 95% CI, 1.1-6.3; P = .04). The probability of achieving pain relief varied between 23% and 75%, depending on these risk factors. CONCLUSIONS The timing of surgery is an important risk factor for clinical outcome in CP. Surgery may need to be considered at an earlier phase than it is now, preferably within 3 years of symptomatic CP. Likelihood of postoperative pain relief can be calculated on an individual basis using the presented nomogram.", "author" : [ { "dropping-particle" : "", "family" : "Ahmed Ali", "given" : "Usama", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nieuwenhuijs", "given" : "Vincent B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eijck", "given" : "Casper H", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gooszen", "given" : "Hein G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dam", "given" : "Ronald M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Busch", "given" : "Olivier R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dijkgraaf", "given" : "Marcel G W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mauritz", "given" : "Femke A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jens", "given" : "Sjoerd", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mast", "given" : "Jay", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goor", "given" : "Harry", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boermeester", "given" : "Marja A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dutch Pancreatitis Study Group", "given" : "for the", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Archives of surgery (Chicago, Ill. : 1960)", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2012", "10", "1" ] ] }, "note" : "NULL", "page" : "925-32", "title" : "Clinical outcome in relation to timing of surgery in chronic pancreatitis: a nomogram to predict pain relief.", "type" : "article-journal", "volume" : "147" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(257)", "plainTextFormattedCitation" : "(257)", "previouslyFormattedCitation" : "(257)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(257). Interestingly, there was also a correlation between the frequency of previous endoscopic interventions and postoperative pain relief, since five or more endoscopic interventions resulted in less frequent pain relief among CP patientsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1001/archsurg.2012.1094", "ISSN" : "1538-3644", "PMID" : "23117832", "abstract" : "OBJECTIVE To evaluate the effect of timing of surgery on the long-term clinical outcome of surgery in chronic pancreatitis (CP). DESIGN Cohort study with long-term follow-up. SETTING Five specialized academic centers. PATIENTS Patients with CP treated surgically for pain. INTERVENTIONS Pancreatic resection and drainage procedures for pain relief. MAIN OUTCOME MEASURES Pain relief (pain visual analogue score \u22644), pancreatic function, and quality of life. RESULTS We included 266 patients with median follow-up of 62 months (interquartile range, 31-112). Results were presented as odds ratios (ORs)with 95% confidence intervals after correction for bias using bootstrap-corrected analysis. Pain relief was achieved in 149 patients (58%). Surgery within 3 years of symptoms was independently associated with more pain relief (OR, 1.8; 95% CI, 1.0-3.4; P = .03) and less endocrine pancreatic insufficiency (OR, 0.57; 95% CI, 0.33-0.96; P = .04). More pain relief was also observed in patients not taking opioids preoperatively (OR, 2.1; 95% CI, 1.2-4.0; P = .006) and who had 5 or fewer endoscopic treatments prior to surgery (OR, 2.5; 95% CI, 1.1-6.3; P = .04). The probability of achieving pain relief varied between 23% and 75%, depending on these risk factors. CONCLUSIONS The timing of surgery is an important risk factor for clinical outcome in CP. Surgery may need to be considered at an earlier phase than it is now, preferably within 3 years of symptomatic CP. Likelihood of postoperative pain relief can be calculated on an individual basis using the presented nomogram.", "author" : [ { "dropping-particle" : "", "family" : "Ahmed Ali", "given" : "Usama", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nieuwenhuijs", "given" : "Vincent B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eijck", "given" : "Casper H", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gooszen", "given" : "Hein G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dam", "given" : "Ronald M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Busch", "given" : "Olivier R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dijkgraaf", "given" : "Marcel G W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mauritz", "given" : "Femke A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jens", "given" : "Sjoerd", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mast", "given" : "Jay", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goor", "given" : "Harry", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boermeester", "given" : "Marja A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dutch Pancreatitis Study Group", "given" : "for the", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Archives of surgery (Chicago, Ill. : 1960)", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2012", "10", "1" ] ] }, "note" : "NULL", "page" : "925-32", "title" : "Clinical outcome in relation to timing of surgery in chronic pancreatitis: a nomogram to predict pain relief.", "type" : "article-journal", "volume" : "147" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(257)", "plainTextFormattedCitation" : "(257)", "previouslyFormattedCitation" : "(257)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(257). In another cohort study with 55 patients from the UK, Terrace et al. analyzed the impact of pancreatic drainage surgery (longitudinal pancreatico-jejunostomy) with Frey’s procedure (that involves coring of the pancreatic head)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/13651820701481497", "ISSN" : "1365-182X", "PMID" : "18345310", "abstract" : "INTRODUCTION A vast majority of patients with chronic pancreatitis require regular opiate/opioid analgesia and recurrent hospital admission for pain. However, the role and timing of operative strategies for pain in chronic pancreatitis is controversial. This study hypothesized that pancreatic decompression surgery reduces analgesia requirement and hospital readmission for pain in selected patients. PATIENTS AND METHODS This was a retrospective review of patients undergoing longitudinal pancreatico-jejunostomy (LPJ), with or without coring of the pancreatic head (Frey's procedure), between 1995 and 2007 in a single UK centre. Surgery was performed for chronic pain with clinical/radiological evidence of chronic pancreatitis amenable to decompression/head coring. RESULTS Fifty patients were identified. Thirty-six were male with a median age of 46 years and median follow-up of 30 months. Twenty-eight underwent LPJ and 22 underwent Frey's procedure. No significant difference in reduction of analgesia requirement (71% vs 64%, p=0.761) or hospital readmission for pain (21% vs 23%, p=1.000) was observed when comparing LPJ and Frey's procedure. Patients were significantly more likely to be pain-free following surgery if they required non-opiate rather than opiate analgesia preoperatively (75% vs 19%, p=0.0002). Fewer patients required subsequent hospital readmission for pain if taking non-opiate rather than opiate analgesia preoperatively (12.5% vs 31%, p=0.175). CONCLUSIONS In selected patients, LPJ and Frey's procedure have equivalent benefit in short-term pain reduction. Patients should be selected for surgery before the commencement of opiate analgesia.", "author" : [ { "dropping-particle" : "", "family" : "Terrace", "given" : "J D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Paterson", "given" : "H M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Garden", "given" : "O J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parks", "given" : "R W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Madhavan", "given" : "K K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "HPB : the official journal of the International Hepato Pancreato Biliary Association", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2007", "8" ] ] }, "note" : "NULL", "page" : "308-11", "title" : "Results of decompression surgery for pain in chronic pancreatitis.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(343)", "plainTextFormattedCitation" : "(343)", "previouslyFormattedCitation" : "(343)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(343). Here, there were comparable reductions rates in analgesia requirement, but patients who were not on opiods were likely to be pain-free after surgery than patients who had required opioidsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/13651820701481497", "ISSN" : "1365-182X", "PMID" : "18345310", "abstract" : "INTRODUCTION A vast majority of patients with chronic pancreatitis require regular opiate/opioid analgesia and recurrent hospital admission for pain. However, the role and timing of operative strategies for pain in chronic pancreatitis is controversial. This study hypothesized that pancreatic decompression surgery reduces analgesia requirement and hospital readmission for pain in selected patients. PATIENTS AND METHODS This was a retrospective review of patients undergoing longitudinal pancreatico-jejunostomy (LPJ), with or without coring of the pancreatic head (Frey's procedure), between 1995 and 2007 in a single UK centre. Surgery was performed for chronic pain with clinical/radiological evidence of chronic pancreatitis amenable to decompression/head coring. RESULTS Fifty patients were identified. Thirty-six were male with a median age of 46 years and median follow-up of 30 months. Twenty-eight underwent LPJ and 22 underwent Frey's procedure. No significant difference in reduction of analgesia requirement (71% vs 64%, p=0.761) or hospital readmission for pain (21% vs 23%, p=1.000) was observed when comparing LPJ and Frey's procedure. Patients were significantly more likely to be pain-free following surgery if they required non-opiate rather than opiate analgesia preoperatively (75% vs 19%, p=0.0002). Fewer patients required subsequent hospital readmission for pain if taking non-opiate rather than opiate analgesia preoperatively (12.5% vs 31%, p=0.175). CONCLUSIONS In selected patients, LPJ and Frey's procedure have equivalent benefit in short-term pain reduction. Patients should be selected for surgery before the commencement of opiate analgesia.", "author" : [ { "dropping-particle" : "", "family" : "Terrace", "given" : "J D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Paterson", "given" : "H M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Garden", "given" : "O J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parks", "given" : "R W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Madhavan", "given" : "K K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "HPB : the official journal of the International Hepato Pancreato Biliary Association", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2007", "8" ] ] }, "note" : "NULL", "page" : "308-11", "title" : "Results of decompression surgery for pain in chronic pancreatitis.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(343)", "plainTextFormattedCitation" : "(343)", "previouslyFormattedCitation" : "(343)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(343).As also underlined by the recent Cochrane Review on the comparison of endoscopy versus surgery in the management of painful CPADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1469-493X", "author" : [ { "dropping-particle" : "", "family" : "Ahmed Ali", "given" : "Usama", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pahlplatz", "given" : "Johanna M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nealon", "given" : "Wiliam H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goor", "given" : "Harry", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gooszen", "given" : "Hein G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boermeester", "given" : "Marja A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cochrane Database of Systematic Reviews", "editor" : [ { "dropping-particle" : "", "family" : "Ahmed Ali", "given" : "Usama", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "0" ] ] }, "page" : "CD007884", "publisher" : "John Wiley & Sons, Ltd", "publisher-place" : "Chichester, UK", "title" : "Endoscopic or surgical intervention for painful obstructive chronic pancreatitis", "type" : "chapter", "volume" : "1" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(231)", "plainTextFormattedCitation" : "(231)", "previouslyFormattedCitation" : "(231)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(231), the three RCTs on this topic collectively demonstrate that surgery is superior to endoscopy with regard to pain relief both at middle-term (2-5 years) or long-term (>5 years) follow-upADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0003-4932", "PMID" : "8489308", "abstract" : "OBJECTIVE This study evaluated the effect of operative drainage of the main pancreatic duct (MPD) on functional derangements associated with chronic pancreatitis (CP). SUMMARY BACKGROUND DATA The author previously reported delayed functional impairment in an evaluation of the impact of operative drainage in patients with CP. The author now reports on a prospective study of 143 patients with this diagnosis. METHODS Each patient underwent 1) ERCP, 2) the Bentiromide PABA, 3) 72-hour fecal fat test, 4) oral glucose tolerance test (OGTT) and 5) fat meal (LIPOMUL)--stimulated pancreatic polypeptide release (PP). All patients were stratified as mild/moderate (M/M) or severe CP on the basis of a 5-point system that was developed by the author. Patients were studied at 16-month intervals. RESULTS All 143 patients underwent initial and follow-up evaluations in a mean follow-up of 47.3 months; 83 of 143 patients had M/M grade at initial evaluation. Eighty-seven patients underwent (MPD) decompression to relieve abdominal pain. In a separate prospective 17 patients with a diagnosis of CP, a grade of M/M and non-disabling abdominal pain were randomized to operative or non-operative treatment; 9 of these randomized patients were operated upon and 8 were not. No patient improved their grade during follow-up; 47 of 83 M/M patients had operative drainage and 36 did not. This grade was preserved in 41 of 47 (87%) operated patients but in only 8 of the 36 non-operated patients (22%). In the randomized trial, seven of nine operated patients retained their functional status in follow-up, whereas only two of eight patients (25%) randomized to non-operation preserved their functional grade. CONCLUSIONS These data in this large study as well as among a previous randomized sample, support a policy of early operative drainage before the development of irreversible functional impairment in patients with chronic pancreatitis and associated dilation of the main pancreatic duct.", "author" : [ { "dropping-particle" : "", "family" : "Nealon", "given" : "W H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thompson", "given" : "J C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of surgery", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "1993", "5" ] ] }, "note" : "NULL", "page" : "458-66; discussion 466-8", "title" : "Progressive loss of pancreatic function in chronic pancreatitis is delayed by main pancreatic duct decompression. A longitudinal prospective analysis of the modified puestow procedure.", "type" : "article-journal", "volume" : "217" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1055/s-2003-40237", "ISSN" : "0013-726X", "PMID" : "12822088", "abstract" : "BACKGROUND AND STUDY AIMS Invasive treatment for abdominal pain due to chronic pancreatitis may be either surgical or endoscopic, particularly in cases of ductal obstruction. To date, the data published on the effectiveness of these two forms of therapy have been mostly retrospective, and there have been no randomized studies. A prospective, randomized study comparing surgery with endoscopy in patients with painful obstructive chronic pancreatitis was therefore conducted. PATIENTS AND METHODS Consecutive patients with pancreatic duct obstruction and pain were invited to participate in a randomized trial comparing endotherapy and surgery, the latter consisting of resection and drainage procedures, depending on the patient's individual situation. Patients who did not agree to participation and randomization were also further assessed using the same follow-up protocol. RESULTS Of 140 eligible patients, only 72 agreed to be randomized. Surgery consisted of resection (80 %) and drainage (20 %) procedures, while endotherapy included sphincterotomy and stenting (52 %) and/or stone removal (23 %). In the entire group, the initial success rates were similar for both groups, but at the 5-year follow-up, complete absence of pain was more frequent after surgery (37 % vs. 14 %), with the rate of partial relief being similar (49 % vs. 51 %). In the randomized subgroup, results were similar (pain absence 34 % after surgery vs. 15 % after endotherapy, relief 52 % after surgery vs. 46 % after endotherapy). The increase in body weight was also greater by 20 - 25 % in the surgical group, while new-onset diabetes developed with similar frequency in both groups (34 - 43 %), again with no differences between the results for the whole group and the randomized subgroup. CONCLUSIONS Surgery is superior to endotherapy for long-term pain reduction in patients with painful obstructive chronic pancreatitis. Better selection of patients for endotherapy may be helpful in order to maximize results. Due to its low degree of invasiveness, however, endotherapy can be offered as a first-line treatment, with surgery being performed in case of failure and/or recurrence.", "author" : [ { "dropping-particle" : "", "family" : "D\u00edte", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruzicka", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zboril", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Novotn\u00fd", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Endoscopy", "id" : "ITEM-2", "issue" : "7", "issued" : { "date-parts" : [ [ "2003", "7" ] ] }, "note" : "NULL", "page" : "553-558", "title" : "A Prospective, Randomized Trial Comparing Endoscopic and Surgical Therapy for Chronic Pancreatitis", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1056/NEJMoa060610", "ISSN" : "0028-4793", "PMID" : "17301298", "abstract" : "BACKGROUND For patients with chronic pancreatitis and a dilated pancreatic duct, ductal decompression is recommended. We conducted a randomized trial to compare endoscopic and surgical drainage of the pancreatic duct. METHODS All symptomatic patients with chronic pancreatitis and a distal obstruction of the pancreatic duct but without an inflammatory mass were eligible for the study. We randomly assigned patients to undergo endoscopic transampullary drainage of the pancreatic duct or operative pancreaticojejunostomy. The primary end point was the average Izbicki pain score during 2 years of follow-up. The secondary end points were pain relief at the end of follow-up, physical and mental health, morbidity, mortality, length of hospital stay, number of procedures undergone, and changes in pancreatic function. RESULTS Thirty-nine patients underwent randomization: 19 to endoscopic treatment (16 of whom underwent lithotripsy) and 20 to operative pancreaticojejunostomy. During the 24 months of follow-up, patients who underwent surgery, as compared with those who were treated endoscopically, had lower Izbicki pain scores (25 vs. 51, P<0.001) and better physical health summary scores on the Medical Outcomes Study 36-Item Short-Form General Health Survey questionnaire (P=0.003). At the end of follow-up, complete or partial pain relief was achieved in 32% of patients assigned to endoscopic drainage as compared with 75% of patients assigned to surgical drainage (P=0.007). Rates of complications, length of hospital stay, and changes in pancreatic function were similar in the two treatment groups, but patients receiving endoscopic treatment required more procedures than did patients in the surgery group (a median of eight vs. three, P<0.001). CONCLUSIONS Surgical drainage of the pancreatic duct was more effective than endoscopic treatment in patients with obstruction of the pancreatic duct due to chronic pancreatitis. (Current Controlled Trials number, ISRCTN04572410 [controlled-].).", "author" : [ { "dropping-particle" : "", "family" : "Cahen", "given" : "Djuna L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gouma", "given" : "Dirk J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nio", "given" : "Yung", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rauws", "given" : "Erik A. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boermeester", "given" : "Marja A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Busch", "given" : "Olivier R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stoker", "given" : "Jaap", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lam\u00e9ris", "given" : "Johan S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dijkgraaf", "given" : "Marcel G.W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huibregtse", "given" : "Kees", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruno", "given" : "Marco J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "New England Journal of Medicine", "id" : "ITEM-3", "issue" : "7", "issued" : { "date-parts" : [ [ "2007", "2", "15" ] ] }, "page" : "676-684", "title" : "Endoscopic versus Surgical Drainage of the Pancreatic Duct in Chronic Pancreatitis", "type" : "article-journal", "volume" : "356" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(232,233,344)", "plainTextFormattedCitation" : "(232,233,344)", "previouslyFormattedCitation" : "(232,233,344)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(232,233,344). Furthermore, early surgery was proposed to provide better pain relief and pancreatic function when compared to a conservative approach, yet based on the results of a single, old RCT with a small cohort and absent sample size calculationADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0003-4932", "PMID" : "8489308", "abstract" : "OBJECTIVE This study evaluated the effect of operative drainage of the main pancreatic duct (MPD) on functional derangements associated with chronic pancreatitis (CP). SUMMARY BACKGROUND DATA The author previously reported delayed functional impairment in an evaluation of the impact of operative drainage in patients with CP. The author now reports on a prospective study of 143 patients with this diagnosis. METHODS Each patient underwent 1) ERCP, 2) the Bentiromide PABA, 3) 72-hour fecal fat test, 4) oral glucose tolerance test (OGTT) and 5) fat meal (LIPOMUL)--stimulated pancreatic polypeptide release (PP). All patients were stratified as mild/moderate (M/M) or severe CP on the basis of a 5-point system that was developed by the author. Patients were studied at 16-month intervals. RESULTS All 143 patients underwent initial and follow-up evaluations in a mean follow-up of 47.3 months; 83 of 143 patients had M/M grade at initial evaluation. Eighty-seven patients underwent (MPD) decompression to relieve abdominal pain. In a separate prospective 17 patients with a diagnosis of CP, a grade of M/M and non-disabling abdominal pain were randomized to operative or non-operative treatment; 9 of these randomized patients were operated upon and 8 were not. No patient improved their grade during follow-up; 47 of 83 M/M patients had operative drainage and 36 did not. This grade was preserved in 41 of 47 (87%) operated patients but in only 8 of the 36 non-operated patients (22%). In the randomized trial, seven of nine operated patients retained their functional status in follow-up, whereas only two of eight patients (25%) randomized to non-operation preserved their functional grade. CONCLUSIONS These data in this large study as well as among a previous randomized sample, support a policy of early operative drainage before the development of irreversible functional impairment in patients with chronic pancreatitis and associated dilation of the main pancreatic duct.", "author" : [ { "dropping-particle" : "", "family" : "Nealon", "given" : "W H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thompson", "given" : "J C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of surgery", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "1993", "5" ] ] }, "note" : "NULL", "page" : "458-66; discussion 466-8", "title" : "Progressive loss of pancreatic function in chronic pancreatitis is delayed by main pancreatic duct decompression. A longitudinal prospective analysis of the modified puestow procedure.", "type" : "article-journal", "volume" : "217" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "1469-493X", "author" : [ { "dropping-particle" : "", "family" : "Ahmed Ali", "given" : "Usama", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pahlplatz", "given" : "Johanna M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nealon", "given" : "Wiliam H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goor", "given" : "Harry", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gooszen", "given" : "Hein G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boermeester", "given" : "Marja A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cochrane Database of Systematic Reviews", "editor" : [ { "dropping-particle" : "", "family" : "Ahmed Ali", "given" : "Usama", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "0" ] ] }, "page" : "CD007884", "publisher" : "John Wiley & Sons, Ltd", "publisher-place" : "Chichester, UK", "title" : "Endoscopic or surgical intervention for painful obstructive chronic pancreatitis", "type" : "chapter", "volume" : "1" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(231,344)", "plainTextFormattedCitation" : "(231,344)", "previouslyFormattedCitation" : "(231,344)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(231,344). 571500-5124450022860062230Figure 4: Timing of surgery in chronic pancreatitis Surgery is increasingly considered to be more effective for treating pain in CP, if considered early, i.e. within the 2-3 years after diagnosis, and if only a limited number of endoscopic therapy attempts (max. 3) have been made. Later surgery, i.e. after three years of diagnosis, may not provide the same degree of effectiveness in pain relief as early surgery.00Figure 4: Timing of surgery in chronic pancreatitis Surgery is increasingly considered to be more effective for treating pain in CP, if considered early, i.e. within the 2-3 years after diagnosis, and if only a limited number of endoscopic therapy attempts (max. 3) have been made. Later surgery, i.e. after three years of diagnosis, may not provide the same degree of effectiveness in pain relief as early surgery.Collectively, current evidence on the timing of surgery for painful CP suggests a beneficial role for early surgery, i.e. 1) within the first 2 to 3 years after diagnosis or symptom onset, 2) for patients who had equal to or fewer than 5 endoscopic procedures, and 3) for patients who have not yet required opioid analgesics for medical pain treatment (Figure 4). These recommendations still need to evaluated in the context of novel, better designed RCTs comparing surgery with other measures in the early phase of CP. Encouragingly, the Dutch Chronic Pancreatitis Registry (CARE) has already collected detailed records on the pain and other characteristics of 1,218 patients from 33 hospitals and is likely to provide a solid basis for the role of early surgery in the management of painful CP. Moreover, the ESCAPE trial (“Early surgery?versus optimal current step-up practice for?chronic pancreatitis”), which is currently recruiting, represents the most current RCT that will yield important results toward answering the question on the timing of surgery for CPADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1186/1471-230X-13-49", "ISSN" : "1471-230X", "PMID" : "23506415", "abstract" : "BACKGROUND In current practice, patients with chronic pancreatitis undergo surgical intervention in a late stage of the disease, when conservative treatment and endoscopic interventions have failed. Recent evidence suggests that surgical intervention early on in the disease benefits patients in terms of better pain control and preservation of pancreatic function. Therefore, we designed a randomized controlled trial to evaluate the benefits, risks and costs of early surgical intervention compared to the current stepwise practice for chronic pancreatitis. METHODS/DESIGN The ESCAPE trial is a randomized controlled, parallel, superiority multicenter trial. Patients with chronic pancreatitis, a dilated pancreatic duct (\u22655 mm) and moderate pain and/or frequent flare-ups will be registered and followed monthly as potential candidates for the trial. When a registered patient meets the randomization criteria (i.e. need for opioid analgesics) the patient will be randomized to either early surgical intervention (group A) or optimal current step-up practice (group B). An expert panel of chronic pancreatitis specialists will oversee the assessment of eligibility and ensure that allocation to either treatment arm is possible. Patients in group A will undergo pancreaticojejunostomy or a Frey-procedure in case of an enlarged pancreatic head (\u22654 cm). Patients in group B will undergo a step-up practice of optimal medical treatment, if needed followed by endoscopic interventions, and if needed followed by surgery, according to predefined criteria. Primary outcome is pain assessed with the Izbicki pain score during a follow-up of 18 months. Secondary outcomes include complications, mortality, total direct and indirect costs, quality of life, pancreatic insufficiency, alternative pain scales, length of hospital admission, number of interventions and pancreatitis flare-ups. For the sample size calculation we defined a minimal clinically relevant difference in the primary endpoint as a difference of at least 15 points on the Izbicki pain score during follow-up. To detect this difference a total of 88 patients will be randomized (alpha 0.05, power 90%, drop-out 10%). DISCUSSION The ESCAPE trial will investigate whether early surgery in chronic pancreatitis is beneficial in terms of pain relief, pancreatic function and quality of life, compared with current step-up practice. TRIAL REGISTRATION ISRCTN: ISRCTN45877994.", "author" : [ { "dropping-particle" : "", "family" : "Ahmed Ali", "given" : "Usama", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Issa", "given" : "Yama", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruno", "given" : "Marco J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goor", "given" : "Harry", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Santvoort", "given" : "Hjalmar", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Busch", "given" : "Olivier R C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dejong", "given" : "Cornelis H C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nieuwenhuijs", "given" : "Vincent B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eijck", "given" : "Casper H", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dullemen", "given" : "Hendrik M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fockens", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siersema", "given" : "Peter D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gouma", "given" : "Dirk J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hooft", "given" : "Jeanin E", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keulemans", "given" : "Yolande", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Poley", "given" : "Jan W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Timmer", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Besselink", "given" : "Marc G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vleggaar", "given" : "Frank P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "Oliver H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gooszen", "given" : "Hein G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dijkgraaf", "given" : "Marcel G W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boermeester", "given" : "Marja A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dutch Pancreatitis Study Group", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMC gastroenterology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2013", "3", "18" ] ] }, "note" : "NULL", "page" : "49", "title" : "Early surgery versus optimal current step-up practice for chronic pancreatitis (ESCAPE): design and rationale of a randomized trial.", "type" : "article-journal", "volume" : "13" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(324)", "plainTextFormattedCitation" : "(324)", "previouslyFormattedCitation" : "(324)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(324). In this study, the investigators reported that patients with a dilated pancreatic duct (≥5 mm) and moderate pain and/or frequent flare-ups are going to be monitored for randomization criteria (e.g. need for opioid analgesics)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1186/1471-230X-13-49", "ISSN" : "1471-230X", "PMID" : "23506415", "abstract" : "BACKGROUND In current practice, patients with chronic pancreatitis undergo surgical intervention in a late stage of the disease, when conservative treatment and endoscopic interventions have failed. Recent evidence suggests that surgical intervention early on in the disease benefits patients in terms of better pain control and preservation of pancreatic function. Therefore, we designed a randomized controlled trial to evaluate the benefits, risks and costs of early surgical intervention compared to the current stepwise practice for chronic pancreatitis. METHODS/DESIGN The ESCAPE trial is a randomized controlled, parallel, superiority multicenter trial. Patients with chronic pancreatitis, a dilated pancreatic duct (\u22655 mm) and moderate pain and/or frequent flare-ups will be registered and followed monthly as potential candidates for the trial. When a registered patient meets the randomization criteria (i.e. need for opioid analgesics) the patient will be randomized to either early surgical intervention (group A) or optimal current step-up practice (group B). An expert panel of chronic pancreatitis specialists will oversee the assessment of eligibility and ensure that allocation to either treatment arm is possible. Patients in group A will undergo pancreaticojejunostomy or a Frey-procedure in case of an enlarged pancreatic head (\u22654 cm). Patients in group B will undergo a step-up practice of optimal medical treatment, if needed followed by endoscopic interventions, and if needed followed by surgery, according to predefined criteria. Primary outcome is pain assessed with the Izbicki pain score during a follow-up of 18 months. Secondary outcomes include complications, mortality, total direct and indirect costs, quality of life, pancreatic insufficiency, alternative pain scales, length of hospital admission, number of interventions and pancreatitis flare-ups. For the sample size calculation we defined a minimal clinically relevant difference in the primary endpoint as a difference of at least 15 points on the Izbicki pain score during follow-up. To detect this difference a total of 88 patients will be randomized (alpha 0.05, power 90%, drop-out 10%). DISCUSSION The ESCAPE trial will investigate whether early surgery in chronic pancreatitis is beneficial in terms of pain relief, pancreatic function and quality of life, compared with current step-up practice. TRIAL REGISTRATION ISRCTN: ISRCTN45877994.", "author" : [ { "dropping-particle" : "", "family" : "Ahmed Ali", "given" : "Usama", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Issa", "given" : "Yama", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruno", "given" : "Marco J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goor", "given" : "Harry", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Santvoort", "given" : "Hjalmar", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Busch", "given" : "Olivier R C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dejong", "given" : "Cornelis H C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nieuwenhuijs", "given" : "Vincent B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eijck", "given" : "Casper H", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dullemen", "given" : "Hendrik M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fockens", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siersema", "given" : "Peter D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gouma", "given" : "Dirk J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hooft", "given" : "Jeanin E", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keulemans", "given" : "Yolande", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Poley", "given" : "Jan W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Timmer", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Besselink", "given" : "Marc G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vleggaar", "given" : "Frank P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilder-Smith", "given" : "Oliver H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gooszen", "given" : "Hein G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dijkgraaf", "given" : "Marcel G W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boermeester", "given" : "Marja A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dutch Pancreatitis Study Group", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMC gastroenterology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2013", "3", "18" ] ] }, "note" : "NULL", "page" : "49", "title" : "Early surgery versus optimal current step-up practice for chronic pancreatitis (ESCAPE): design and rationale of a randomized trial.", "type" : "article-journal", "volume" : "13" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(324)", "plainTextFormattedCitation" : "(324)", "previouslyFormattedCitation" : "(324)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(324). Even though this requirement for opioid analgetics represents a potential confounder that may mask the potential beneficial effects of surgery for these patients, this study is still likely to allow a comparison between the duration of the disease and the benefit from surgery versus medical step-up treatment. Until the advent of its results and further well-designed RCTs, early surgery should be assumed to be the superior option in the management of painful CP. However, this recommendation of early surgery, i.e. drainage (e.g. Puestow) or resection (Beger, Frey or Büchler), does not hold for total pancreatectomy with islet auto-transplantation (TPIAT), since this procedure is currently recommended for CP patients with severe impairment of quality of life and for those who are already on opioid analgesicsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/SLA.0000000000001059", "ISSN" : "0003-4932", "PMID" : "25599324", "abstract" : "A workshop sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases focused on research gaps and opportunities in total pancreatectomy with islet autotransplantation (TPIAT) for the management of chronic pancreatitis. The session was held on July 23, 2014 and structured into 5 sessions: (1) patient selection, indications, and timing; (2) technical aspects of TPIAT; (3) improving success of islet autotransplantation; (4) improving outcomes after total pancreatectomy; and (5) registry considerations for TPIAT. The current state of knowledge was reviewed; knowledge gaps and research needs were specifically highlighted. Common themes included the need to identify which patients best benefit from and when to intervene with TPIAT, current limitations of the surgical procedure, diabetes remission and the potential for improvement, opportunities to better address pain remission, GI complications in this population, and unique features of children with chronic pancreatitis considered for TPIAT. The need for a multicenter patient registry that specifically addresses the complexities of chronic pancreatitis and total pancreatectomy outcomes and postsurgical diabetes outcomes was repeatedly emphasized.", "author" : [ { "dropping-particle" : "", "family" : "Bellin", "given" : "Melena D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gelrud", "given" : "Andres", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arreaza-Rubin", "given" : "Guillermo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dunn", "given" : "Ty B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Humar", "given" : "Abhinav", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morgan", "given" : "Katherine A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Naziruddin", "given" : "Bashoo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rastellini", "given" : "Cristiana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rickels", "given" : "Michael R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwarzenberg", "given" : "Sarah J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andersen", "given" : "Dana K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of Surgery", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2015", "1" ] ] }, "note" : "NULL", "page" : "21-29", "title" : "Total Pancreatectomy With Islet Autotransplantation", "type" : "article-journal", "volume" : "261" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(345)", "plainTextFormattedCitation" : "(345)", "previouslyFormattedCitation" : "(345)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(345). Whether also this more invasive procedure (that has a higher risk of postoperative diabetes) should be considered at an earlier phase of painful CP is a matter of current and future investigation. Finally, more work is needed to establish the etiology of pain and if possible tailor the type of surgery accordingly. Hence, surgery may not be sufficiently beneficial in patients where the pain has a strong neurogenic originADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nrgastro.2015.166", "ISSN" : "1759-5045", "PMID" : "26460352", "abstract" : "Pancreatic nerves undergo prominent alterations during the evolution and progression of human chronic pancreatitis and pancreatic cancer. Intrapancreatic nerves increase in size (neural hypertrophy) and number (increased neural density). The proportion of autonomic and sensory fibres (neural remodelling) is switched, and are infiltrated by perineural inflammatory cells (pancreatic neuritis) or invaded by pancreatic cancer cells (neural invasion). These neuropathic alterations also correlate with neuropathic pain. Instead of being mere histopathological manifestations of disease progression, pancreatic neural plasticity synergizes with the enhanced excitability of sensory neurons, with Schwann cell recruitment toward cancer and with central nervous system alterations. These alterations maintain a bidirectional interaction between nerves and non-neural pancreatic cells, as demonstrated by tissue and neural damage inducing neuropathic pain, and activated neurons releasing mediators that modulate inflammation and cancer growth. Owing to the prognostic effects of pain and neural invasion in pancreatic cancer, dissecting the mechanism of pancreatic neuroplasticity holds major translational relevance. However, current in vivo models of pancreatic cancer and chronic pancreatitis contain many discrepancies from human disease that overshadow their translational value. The present Review discusses novel possibilities for mechanistically uncovering the role of the nervous system in pancreatic disease progression.", "author" : [ { "dropping-particle" : "", "family" : "Demir", "given" : "Ihsan Ekin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Friess", "given" : "Helmut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ceyhan", "given" : "G\u00fcralp O.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature Reviews Gastroenterology & Hepatology", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2015", "10", "13" ] ] }, "note" : "NULL", "page" : "649-659", "title" : "Neural plasticity in pancreatitis and pancreatic cancer", "type" : "article-journal", "volume" : "12" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(346)", "plainTextFormattedCitation" : "(346)", "previouslyFormattedCitation" : "(346)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(346). Although no solid evidence from human studies is available, it is plausible that such neuropathy may increase over time and thus justify the role of early surgery. In patients with obstruction of the duct system, surgery may play an even more prominent role, and timing can be decisive for the outcome. Hence, studies that explore pain mechanisms in CP further are still very much needed.Ihsan Ekin Demir, Shuji IsajiQ 12. How to manage pain "relapse" after surgery or endoscopy for painful CP?Current evidence suggests that the first step for the management of pain relapse should be exclusion of obstructing stones or strictured anastomosis via imaging, followed by a limited number endoscopic interventions, and early consideration of re-surgery to achieve pain control (Quality assessment: weak; Recommendation: strong; Agreement: weak).The management of pain in CP includes medical (medication-based), endoscopic, or surgical arms. Among these, surgery has been traditionally reserved for cases that are refractory to medical or endoscopic treatment and proposed as last resort within a “step-up” approach. Recent data, though, indicate that surgery performed at an earlier phase of CP, i.e. within the first three years of symptom onset, or prior to numerous endoscopic interventions, may yield clearly better pain relief than late surgeryADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1001/archsurg.2012.1094", "ISSN" : "1538-3644", "PMID" : "23117832", "abstract" : "OBJECTIVE To evaluate the effect of timing of surgery on the long-term clinical outcome of surgery in chronic pancreatitis (CP). DESIGN Cohort study with long-term follow-up. SETTING Five specialized academic centers. PATIENTS Patients with CP treated surgically for pain. INTERVENTIONS Pancreatic resection and drainage procedures for pain relief. MAIN OUTCOME MEASURES Pain relief (pain visual analogue score \u22644), pancreatic function, and quality of life. RESULTS We included 266 patients with median follow-up of 62 months (interquartile range, 31-112). Results were presented as odds ratios (ORs)with 95% confidence intervals after correction for bias using bootstrap-corrected analysis. Pain relief was achieved in 149 patients (58%). Surgery within 3 years of symptoms was independently associated with more pain relief (OR, 1.8; 95% CI, 1.0-3.4; P = .03) and less endocrine pancreatic insufficiency (OR, 0.57; 95% CI, 0.33-0.96; P = .04). More pain relief was also observed in patients not taking opioids preoperatively (OR, 2.1; 95% CI, 1.2-4.0; P = .006) and who had 5 or fewer endoscopic treatments prior to surgery (OR, 2.5; 95% CI, 1.1-6.3; P = .04). The probability of achieving pain relief varied between 23% and 75%, depending on these risk factors. CONCLUSIONS The timing of surgery is an important risk factor for clinical outcome in CP. Surgery may need to be considered at an earlier phase than it is now, preferably within 3 years of symptomatic CP. Likelihood of postoperative pain relief can be calculated on an individual basis using the presented nomogram.", "author" : [ { "dropping-particle" : "", "family" : "Ahmed Ali", "given" : "Usama", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nieuwenhuijs", "given" : "Vincent B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eijck", "given" : "Casper H", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gooszen", "given" : "Hein G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dam", "given" : "Ronald M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Busch", "given" : "Olivier R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dijkgraaf", "given" : "Marcel G W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mauritz", "given" : "Femke A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jens", "given" : "Sjoerd", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mast", "given" : "Jay", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goor", "given" : "Harry", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boermeester", "given" : "Marja A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dutch Pancreatitis Study Group", "given" : "for the", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Archives of surgery (Chicago, Ill. : 1960)", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2012", "10", "1" ] ] }, "note" : "NULL", "page" : "925-32", "title" : "Clinical outcome in relation to timing of surgery in chronic pancreatitis: a nomogram to predict pain relief.", "type" : "article-journal", "volume" : "147" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1007/s11605-014-2571-8", "ISSN" : "1873-4626", "PMID" : "24944153", "abstract" : "BACKGROUND Surgical intervention has traditionally been reserved as the last management option for pain in chronic pancreatitis. Recently, there has been a call for surgery to be offered earlier in the disease process. The objectives of this review were to evaluate the effect of early surgery on postoperative pain, pancreatic function, and re-intervention rates in chronic pancreatitis. METHODS A systematic literature search through EMBASE, Cochrane Review, and PubMed from January 1950 to January 2014 was conducted. Citations found in relevant papers are hand-searched. Data which could be pooled were analyzed using Revman (v5.2). Risk of bias analysis was conducted. RESULTS Of the 2,886 potentially eligible studies identified, 11 studies met the inclusion criteria. There was large heterogeneity in the study designs, and studies were conducted over a lengthy time span. Seven studies examined pain, three studies examined pancreatic function, and three studies examined rates of re-intervention. Meta-analysis of the three studies with comparative raw data regarding complete pain relief showed that early surgery was associated with an increased likelihood of complete postoperative pain relief (RR\u2009=\u20091.67, 95% CI 1.09-2.56, p\u2009=\u20090.02). Early surgery was also associated with reduced risk of pancreatic insufficiency and low re-intervention rates. CONCLUSIONS Data from this study supports considering early surgery for pain management in patients with chronic pancreatitis, with the potential of a reduced risk of pancreatic insufficiency and the need for further intervention. Further prospective randomized studies are warranted comparing early surgery against conservative step-up approaches.", "author" : [ { "dropping-particle" : "", "family" : "Yang", "given" : "Catherine J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bliss", "given" : "Lindsay A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schapira", "given" : "Emily F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freedman", "given" : "Steven D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Sing Chau", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Windsor", "given" : "John A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tseng", "given" : "Jennifer F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract", "id" : "ITEM-2", "issue" : "10", "issued" : { "date-parts" : [ [ "2014", "10", "19" ] ] }, "note" : "NULL", "page" : "1863-9", "title" : "Systematic review of early surgery for chronic pancreatitis: impact on pain, pancreatic function, and re-intervention.", "type" : "article-journal", "volume" : "18" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(323,257)", "plainTextFormattedCitation" : "(323,257)", "previouslyFormattedCitation" : "(323,257)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(323,257). After any type of surgery or intervention, though, pain relapse in CP is not uncommon. Indeed, even after the most radical and effective type of intervention, i.e. surgery, the long-term (5-year) pain-freeness lies around 50 to 60% in the largest seriesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s11605-007-0155-6", "ISSN" : "1091-255X", "PMID" : "17534689", "abstract" : "INTRODUCTION Organ complications like biliary or duodenal stenosis as well as intractable pain are current indications for surgery in patients with chronic pancreatitis (CP). We present here our experience with pancreatic resection for CP and focus on the long-term outcome after surgery regarding pain, exocrine/endocrine pancreatic function, and the control of organ complications in 224 patients with a median postoperative follow-up period of 56 months. METHODS During 11 years 272 pancreatic resections were performed in our institution for CP. Perioperative mortality was 1%. Follow-up data using at least standardized questionnaires were available in 224 patients. The types of resection in these 224 patients were Whipple (9%), pylorus-preserving pancreato-duodenectomy (PD) (PPPD; 40%), duodenum-preserving pancreatic head resection (DPPHR; 41%, 50 Frey, 42 Beger), distal (9%) and two central pancreatic resections. Eighty-six of the patients were part of a randomized study comparing PPPD and DPPHR. The perioperative and follow-up (f/up) data were prospectively documented. Exocrine insufficiency was regarded as the presence of steatorrhea and/or the need for oral enzyme supplementation. Multivariate analysis was performed using binary logistic regression. RESULTS Perioperative surgical morbidity was 28% and did not differ between the types of resection. At last f/up 87% of the patients were pain-free (60%) or had pain less frequently than once per week (27%). Thirteen percent had frequent pain, at least once per week (no difference between the operative procedures). A concomitant exocrine insufficiency and former postoperative surgical complications were the strongest independent risk factors for pain and frequent pain at follow-up. At the last f/up 65% had exocrine insufficiency, half of them developed it during the postoperative course. The presence of regional or generalized portal hypertension, a low preoperative body mass index, and a longer preoperative duration of CP were independent risk factors for exocrine insufficiency. Thirty-seven percent of the patients without preoperative diabetes developed de novo diabetes during f/up (no risk factor identified). Both, exocrine and endocrine insufficiencies were independent of the type of surgery. Median weight gain was 2 kg and higher in patients with preoperative malnutrition and in patients without abdominal pain. After PPPD, 8% of the patients had peptic jejunal ulcers, whereas 4% presented with biliary\u2026", "author" : [ { "dropping-particle" : "", "family" : "Riediger", "given" : "Hartwig", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adam", "given" : "Ulrich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fischer", "given" : "Eva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keck", "given" : "Tobias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pfeffer", "given" : "Frank", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hopt", "given" : "Ulrich T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Makowiec", "given" : "Frank", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2007", "8", "10" ] ] }, "note" : "NULL", "page" : "949-59; discussion 959-60", "title" : "Long-term outcome after resection for chronic pancreatitis in 224 patients.", "type" : "article-journal", "volume" : "11" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.amjsurg.2007.08.065", "ISSN" : "1879-1883", "PMID" : "18513691", "abstract" : "BACKGROUND Many patients require surgery for chronic pancreatitis (CP). By combining the essences of the Beger and the Frey procedures, a hybrid procedure was developed: central pancreatic-head resection (CPHR) (Berne technique). METHODS A prospective evaluation of 100 consecutive patients who underwent CPHR for CP between January 2002 and December 2006 was performed. Long-term follow-up, including quality-of-life (QOL) assessment, was carried out. RESULTS The hospital mortality rate was 1%; the surgical morbidity rate was 16%; and the relaparotomy rate was 6%. Mean surgery time was 295 +/- 7 minutes; mean intraoperative blood loss was 763 +/- 75 mL; and the mean postsurgical hospital stay was 11.4 +/- .8 days. After a median follow-up of 41 months, pain was improved in 55% of patients; weight increase occurred in 67% of patients; and insulin-dependent diabetes mellitus developed in 22% of the patients. Comparison of QOL parameters with a German adult control population showed no statistically significant differences. CONCLUSIONS CPHR is a safe surgical option to resolve CP-associated problems. Long-term follow-up QOL after CPHR shows results comparable with date published data after the Beger and the Frey procedures.", "author" : [ { "dropping-particle" : "", "family" : "M\u00fcller", "given" : "Michael W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Friess", "given" : "Helmut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leitzbach", "given" : "Sarah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Michalski", "given" : "Christoph W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berberat", "given" : "Pascal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ceyhan", "given" : "G\u00fcralp O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hinz", "given" : "Ulf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ho", "given" : "Choon-Kiat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "K\u00f6ninger", "given" : "J\u00f6rg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kleeff", "given" : "J\u00f6rg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "B\u00fcchler", "given" : "Markus W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American journal of surgery", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2008", "9" ] ] }, "note" : "NULL", "page" : "364-72", "title" : "Perioperative and follow-up results after central pancreatic head resection (Berne technique) in a consecutive series of patients with chronic pancreatitis.", "type" : "article-journal", "volume" : "196" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1007/s11605-009-1119-9", "ISSN" : "1873-4626", "PMID" : "20033344", "abstract" : "INTRODUCTION Duodenum-preserving pancreatic head resection may be an alternative to pancreatoduodenectomy or drainage procedures for chronic pancreatitis. There are few studies directly comparing the long-term outcome after the operations described by Beger and Frey. METHODS One hundred thirteen patients underwent duodenum-preserving pancreatic head resection for complications of chronic pancreatitis. Follow-up was obtained in 92 patients (42 Beger, 50 Frey, median follow-up almost 5 years). RESULTS Overall/surgery-related perioperative morbidity was 30%/20% (Frey) and 40%/31% (Beger). In long-term follow-up (Frey vs Beger), 62% vs 50% were completely free of pain, but 6% vs 19% had pain at least once per week or daily, and 32% vs 31% experienced pain attacks at least once per year (n.s.). Diabetes mellitus occurred in 60% vs 57% (de novo 34% vs 17%). Rates of exocrine insufficiency were 76% vs. 74% (de novo 34% vs. 33%). Median gain in body weight was 2.5 vs 1.5 kg (n.s.), respectively. Four patients had clinically relevant biliary complications during follow-up requiring reintervention. CONCLUSIONS Our (nonrandomized) comparison of the long-term outcome after Frey and Beger procedures for chronic pancreatitis reveals a tendency for better pain control with the Frey operation. The functional outcomes were almost identical.", "author" : [ { "dropping-particle" : "", "family" : "Keck", "given" : "Tobias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wellner", "given" : "Ulrich Friedrich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Riediger", "given" : "Hartwig", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adam", "given" : "Ulrich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sick", "given" : "Olivia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hopt", "given" : "Ulrich Theodor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Makowiec", "given" : "Frank", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract", "id" : "ITEM-3", "issue" : "3", "issued" : { "date-parts" : [ [ "2010", "3", "22" ] ] }, "note" : "NULL", "page" : "549-56", "title" : "Long-term outcome after 92 duodenum-preserving pancreatic head resections for chronic pancreatitis: comparison of Beger and Frey procedures.", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(337\u2013339)", "plainTextFormattedCitation" : "(337\u2013339)", "previouslyFormattedCitation" : "(337\u2013339)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(337–339). This figure means that half to 40% of all CP patients who underwent surgery for painful CP are eventually going to develop pain relapse. A recent study showed high readmission rates at 30 and 90 days after surgery for CP (including duodenum reserving pancreatic head resection or pancreaticoduodenectomy), reaching 33% at 30 days and 40.5% at 90 days, mainly due to inadequate pain controlADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.surg.2014.06.068", "ISSN" : "00396060", "PMID" : "25239319", "abstract" : "BACKGROUND Readmission after complex gastrointestinal surgery is a frequent occurrence that burdens the health care system and leads to increased cost. Recent studies have demonstrated 30- and 90-day readmission rates of 15% and 19%, respectively, following pancreaticoduodenectomy. Given the psychosocial issues often associated with chronic pancreatitis, we hypothesized that readmission rates following surgery for chronic pancreatitis would be higher than previously reported for pancreaticoduodenectomy. METHODS We retrospectively reviewed patients undergoing surgery for chronic pancreatitis at a single institution between 2001 and 2013. Patients in this cohort underwent pancreaticoduodenectomy, Berne, Beger, or Frey procedures. Readmission to a primary or secondary hospital was evaluated at both 30 and 90\u00a0days after discharge. Multivariate logistic regression analysis was performed to identify factors associated with readmission. RESULTS The records of 111 patients were evaluated, of which 69 (62%) underwent duodenal-preserving pancreatic head resection (Berne, Beger, or Frey), while the remaining 42 (38%) underwent pancreaticoduodenectomy. Within the duodenal-preserving pancreatic head resection arm, readmission rates at 30\u00a0and 90\u00a0days were 30.4% and 43.5%, respectively. Readmission rates following pancreaticoduodenectomy were similar with 33.3% at 30\u00a0days and 40.5% at 90\u00a0days. The most common reasons for readmission were pain control, infectious complications, and recurrent pancreatitis. On multivariate analysis, wound infection during the initial hospital stay was a predictor of readmission at both 30 and 90\u00a0days (P\u00a0=\u00a0.02). CONCLUSION To our knowledge, our data represent the first report demonstrating very high readmission rates after surgery for chronic pancreatitis, more than double the previous rates reported for pancreaticoduodenectomy. This cohort of patients requires extensive discharge planning focused on pain control, nutritional optimization, and close postoperative monitoring.", "author" : [ { "dropping-particle" : "V.", "family" : "Fisher", "given" : "Alexander", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sutton", "given" : "Jeffrey M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilson", "given" : "Gregory C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hanseman", "given" : "Dennis J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abbott", "given" : "Daniel E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Milton T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schmulewitz", "given" : "Nathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Choe", "given" : "Kyran A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Jiang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sussman", "given" : "Jeffrey J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ahmad", "given" : "Syed A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Surgery", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2014", "10" ] ] }, "note" : "NULL", "page" : "787-796", "title" : "High readmission rates after surgery for chronic pancreatitis", "type" : "article-journal", "volume" : "156" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(347)", "plainTextFormattedCitation" : "(347)", "previouslyFormattedCitation" : "(347)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(347). In the medical literature, the management of these cases of pain relapse either after surgery or even endoscopy has not been sufficiently addressed, and high-quality studies are lacking.After endoscopy, some studies with potential selection or publication bias have reported that persistent pain relief after endoscopic treatment (including endoscopic sphincterotomy, dilatation of the pancreatic duct, and stent placement) reached 57% at the five-year follow-upADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3748/wjg.v19.i5.715", "ISSN" : "2219-2840", "PMID" : "23430281", "abstract" : "AIM This study analyzed clinical long-term outcomes after endoscopic therapy, including the incidence and treatment of relapse. METHODS This study included 19 consecutive patients (12 male, 7 female, median age 54 years) with obstructive chronic pancreatitis who were admitted to the 2(nd) Medical Department of the Technical University of Munich. All patients presented severe chronic pancreatitis (stage III\u00b0) according to the Cambridge classification. The majority of the patients suffered intermittent pain attacks. 6 of 19 patients had strictures of the pancreatic duct; 13 of 19 patients had strictures and stones. The first endoscopic retrograde pancreatography (ERP) included an endoscopic sphincterotomy, dilatation of the pancreatic duct, and stent placement. The first control ERP was performed 4 wk after the initial intervention, and the subsequent control ERP was performed after 3 mo to re-evaluate the clinical and morphological conditions. Clinical follow-up was performed annually to document the course of pain and the management of relapse. The course of pain was assessed by a pain scale from 0 to 10. The date and choice of the therapeutic procedure were documented in case of relapse. RESULTS Initial endoscopic intervention was successfully completed in 17 of 19 patients. All 17 patients reported partial or complete pain relief after endoscopic intervention. Endoscopic therapy failed in 2 patients. Both patients were excluded from further analysis. One failed patient underwent surgery, and the other patient was treated conservatively with pain medication. Seventeen of 19 patients were followed after the successful completion of endoscopic stent therapy. Three of 17 patients were lost to follow-up. One patient was not available for interviews after the 1(st) year of follow-up. Two patients died during the 3(rd) year of follow-up. In both patients chronic pancreatitis was excluded as the cause of death. One patient died of myocardial infarction, and one patient succumbed to pneumonia. All three patients were excluded from follow-up analysis. Follow-up was successfully completed in 14 of 17 patients. 4 patients at time point 3, 2 patients at time point 4, 3 patients at time point 5 and 2 patients at time point 6 and time point 7 used continuous pain medication after endoscopic therapy. No relapse occurred in 57% (8/14) of patients. All 8 patients exhibited significantly reduced or no pain complaints during the 5-year follow-up. Seven of 8 patients were\u2026", "author" : [ { "dropping-particle" : "", "family" : "Weber", "given" : "Andreas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schneider", "given" : "Jochen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Neu", "given" : "Bruno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meining", "given" : "Alexander", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Born", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delius", "given" : "Stefan", "non-dropping-particle" : "von", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bajbouj", "given" : "Monther", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schmid", "given" : "Roland M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alg\u00fcl", "given" : "Hana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prinz", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "World journal of gastroenterology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2013", "2", "7" ] ] }, "note" : "NULL", "page" : "715-20", "title" : "Endoscopic stent therapy in patients with chronic pancreatitis: a 5-year follow-up study.", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(280)", "plainTextFormattedCitation" : "(280)", "previouslyFormattedCitation" : "(280)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(280). For patients with pancreas divisum who underwent endotherapy, the response rate, i.e. complete or partial relief rate was reported to be 69.4% and to be comparable to that after surgery (74.9%)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1055/s-0029-1214505", "ISSN" : "1438-8812", "PMID" : "19337962", "abstract" : "BACKGROUND AND STUDY AIMS The rates for endoscopic detection of pancreas divisum at routine endoscopic retrograde cholangiopancreatography (ERCP) vary worldwide, and the sample sizes in the reported studies on endoscopy and surgery for pancreas divisum are very small and variable. The aim of this study was to systematically analyze the pooled data and determine endoscopic detection rates for pancreas divisum and pain relief rates in patients with pancreas divisum after endotherapy or surgery. MATERIALS AND METHODS A search for published data was performed by using the Medline database (1950 to 1st May 2008) with \"pancreas divisum\" as the keyword. Publications, mainly on endoscopic detection rate, endotherapy, or surgery for pancreas divisum, were deemed relevant, and were further fully reviewed and analyzed. RESULTS A total of 615 abstracts were retrieved from Medline; 17 articles on endoscopic detection rate, 15 articles on endotherapy, and 13 articles on surgery were included in the review and analysis. The overall endoscopic detection rate for pancreas divisum was 2.9% (899/31,413), with the rate being significantly higher in the United States (5.8%) and Europe (6.0%) than in Asia (1.5%) (both P < 0.001). The pooled overall response rates (i. e. complete and partial pain relief rates after treatment) to endotherapy (69.4%, 361/520) and surgery (74.9%, 203/271) were similar (P = 0.106). In addition, there were significant differences in the combined response rates (for endotherapy and for surgery) between patients with pancreas divisum of acute recurrent pancreatitis (ARP)-type (81.2 %) compared with chronic pancreatitis-type (68.8%), and between ARP-type and pain-type (53.1%) (both P < 0.05). CONCLUSIONS The endoscopic detection rate for pancreas divisum is much higher in western countries than in Asian countries. The pooled response rates of patients with pancreas divisum to endotherapy and surgery are similar in the reported series. Patients with ARP-type pancreas divisum respond better to endotherapy or surgery than those with chronic pancreatitis-type and pain-type.", "author" : [ { "dropping-particle" : "", "family" : "Liao", "given" : "Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gao", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ye", "given" : "Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lai", "given" : "X-W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "X-T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "L-H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Z-S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Endoscopy", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2009", "5", "31" ] ] }, "note" : "NULL", "page" : "439-44", "title" : "A systematic review on endoscopic detection rate, endotherapy, and surgery for pancreas divisum.", "type" : "article-journal", "volume" : "41" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(348)", "plainTextFormattedCitation" : "(348)", "previouslyFormattedCitation" : "(348)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(348). In a long-term prospective controlled study, Seza et al. performed extracorporeal shock-wave lithotripsy (ESWL) or endoscopic basket extraction of pancreatic stones, followed by stenting or not (control) of the main pancreatic ductADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.5754/hge09346", "ISSN" : "0172-6390", "PMID" : "22234084", "abstract" : "BACKGROUND/AIMS Endoscopic pancreatic stenting (EPS) has been used to treat main pancreatic duct (MPD) stricture in chronic pancreatitis (CP), with favourable reported results. However, most studies were retrospective and uncontrolled. We conducted a longterm prospective controlled study of EPS for treatment of MPD stricture in CP. METHODOLOGY Consecutive patients with CP were treated to remove pancreatic stones by extracorporeal shock-wave lithotripsy or endoscopic basket extraction. After treatment, 41 patients were enrolled in the study upon meeting the criteria of complete removal of stones, pain relief after the treatment, and dominant stricture of the MPD. Twenty patients chose EPS, while 22 control patients did not. We compared recurrence of pain and pancreatic function between groups for over 3 years of follow-up. RESULTS The mean follow-up period was 62.5 \u00b1 20.9 months. Pain recurred in 15% of EPS patients (3/20) and in 50.0% of control patients (11/22), a significant difference (p<0.05). Progression of exocrine insufficiency in the EPS group was significantly slower than in the control group (p<0.05), while endocrine function showed no difference between groups. CONCLUSIONS EPS reduced pain recurrence and slowed down the progression of exocrine insufficiency in CP patients with MPD stricture.", "author" : [ { "dropping-particle" : "", "family" : "Seza", "given" : "Katsushi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamaguchi", "given" : "Taketo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ishihara", "given" : "Takeshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tadenema", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tawada", "given" : "Katsunobu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saisho", "given" : "Hiromitsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yokosuka", "given" : "Osamu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Hepato-gastroenterology", "id" : "ITEM-1", "issue" : "112", "issued" : { "date-parts" : [ [ "0" ] ] }, "note" : "NULL", "page" : "2128-31", "title" : "A long-term controlled trial of endoscopic pancreatic stenting for treatment of main pancreatic duct stricture in chronic pancreatitis.", "type" : "article-journal", "volume" : "58" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(349)", "plainTextFormattedCitation" : "(349)", "previouslyFormattedCitation" : "(349)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(349). The recurrence rates were 15% in the stented vs. 50% in the control group at the five-year follow-upADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.5754/hge09346", "ISSN" : "0172-6390", "PMID" : "22234084", "abstract" : "BACKGROUND/AIMS Endoscopic pancreatic stenting (EPS) has been used to treat main pancreatic duct (MPD) stricture in chronic pancreatitis (CP), with favourable reported results. However, most studies were retrospective and uncontrolled. We conducted a longterm prospective controlled study of EPS for treatment of MPD stricture in CP. METHODOLOGY Consecutive patients with CP were treated to remove pancreatic stones by extracorporeal shock-wave lithotripsy or endoscopic basket extraction. After treatment, 41 patients were enrolled in the study upon meeting the criteria of complete removal of stones, pain relief after the treatment, and dominant stricture of the MPD. Twenty patients chose EPS, while 22 control patients did not. We compared recurrence of pain and pancreatic function between groups for over 3 years of follow-up. RESULTS The mean follow-up period was 62.5 \u00b1 20.9 months. Pain recurred in 15% of EPS patients (3/20) and in 50.0% of control patients (11/22), a significant difference (p<0.05). Progression of exocrine insufficiency in the EPS group was significantly slower than in the control group (p<0.05), while endocrine function showed no difference between groups. CONCLUSIONS EPS reduced pain recurrence and slowed down the progression of exocrine insufficiency in CP patients with MPD stricture.", "author" : [ { "dropping-particle" : "", "family" : "Seza", "given" : "Katsushi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamaguchi", "given" : "Taketo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ishihara", "given" : "Takeshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tadenema", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tawada", "given" : "Katsunobu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saisho", "given" : "Hiromitsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yokosuka", "given" : "Osamu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Hepato-gastroenterology", "id" : "ITEM-1", "issue" : "112", "issued" : { "date-parts" : [ [ "0" ] ] }, "note" : "NULL", "page" : "2128-31", "title" : "A long-term controlled trial of endoscopic pancreatic stenting for treatment of main pancreatic duct stricture in chronic pancreatitis.", "type" : "article-journal", "volume" : "58" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(349)", "plainTextFormattedCitation" : "(349)", "previouslyFormattedCitation" : "(349)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(349). In a randomized controlled trial comparing ESWL in combination with endoscopy with ESWL alone, Dumonceau et al. reported 38% pain relapse after ESWL alone and 45% pain relapse after ESWL combined with endoscopyADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/gut.2006.096883", "ISSN" : "0017-5749", "PMID" : "17047101", "abstract" : "BACKGROUND In chronic pancreatitis, obstruction of the main pancreatic duct (MPD) may contribute to the pathogenesis of pain. Pilot studies suggest that extracorporeal shock wave lithotripsy (ESWL) alone relieves pain in calcified chronic pancreatitis. AIM To compare ESWL alone with ESWL and endoscopic drainage of the MPD for treatment of pain in chronic pancreatitis. SUBJECTS Patients with uncomplicated painful chronic pancreatitis and calcifications obstructing the MPD. METHODS 55 patients were randomised to ESWL alone (n = 26) or ESWL combined with endoscopy (n = 29). RESULTS 2 years after trial intervention, 10 (38%) and 13 (45%) patients of the ESWL alone and ESWL combined with endoscopy group, respectively, had presented pain relapse (primary outcome) (OR 0.77; 95% CI 0.23 to 2.57). In both groups, a similar decrease was seen after treatment in the MPD diameter (mean decrease 1.7 mm; 95% CI 0.9 to 2.6; p<0.001), and in the number of pain episodes/year (mean decrease, 3.7; 95% CI 2.6 to 4.9; p<0.001). Treatment costs per patient were three times higher in the ESWL combined with endoscopy group compared with the ESWL alone group (p = 0.001). The median delay between the onset of chronic pancreatitis and persistent pain relief for both groups was 1.1 year (95% CI 0.7 to 1.6), as compared with 4 years (95% CI 3 to 4) for the natural history of chronic pancreatitis in a reference cohort (p<0.001). CONCLUSIONS ESWL is a safe and effective preferred treatment for selected patients with painful calcified chronic pancreatitis. Combining systematic endoscopy with ESWL adds to the cost of patient care, without improving the outcome of pancreatic pain.", "author" : [ { "dropping-particle" : "", "family" : "Dumonceau", "given" : "Jean-Marc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Costamagna", "given" : "Guido", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tringali", "given" : "Andrea", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vahedi", "given" : "Kouroche", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delhaye", "given" : "Myriam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hittelet", "given" : "Axel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spera", "given" : "Gianluca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giostra", "given" : "Emiliano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mutignani", "given" : "Massimiliano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maertelaer", "given" : "Viviane", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devi\u00e8re", "given" : "Jacques", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gut", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2007", "4", "1" ] ] }, "note" : "NULL", "page" : "545-52", "title" : "Treatment for painful calcified chronic pancreatitis: extracorporeal shock wave lithotripsy versus endoscopic treatment: a randomised controlled trial.", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(261)", "plainTextFormattedCitation" : "(261)", "previouslyFormattedCitation" : "(261)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(261), rendering the benefit from additional endoscopy after ESWL questionable. In the largest retrospective cohort (n=636) of ESWL reported in the literature, 68.7% of the patients were pain-free, 25.4% had mild-to-moderate?pain, and 5.5% had severe?pain at 2 to 5 years of follow-up. In the long-term group (longer than 60 months follow-up), 60.3% had no?pain, 35.7% had mild or moderate episodes of?pain, and 4.04%severe?painADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.gie.2013.05.012", "ISSN" : "1097-6779", "PMID" : "23891416", "abstract" : "BACKGROUND Long-term results of extracorporeal shockwave lithotripsy (ESWL) for large pancreatic duct (PD) stones in patients with idiopathic calcific pancreatitis (CP) are scanty. OBJECTIVE To evaluate intermediate and long-term results of ESWL in a large cohort of patients with idiopathic CP. DESIGN Cross-sectional study; retrospective chart review. SETTING A high-volume, tertiary-care center for endoscopy and GI diseases. PATIENTS A total of 636 patients with idiopathic CP who underwent ESWL and ERCP were followed-up. Patients were divided into intermediate (24-60 months) and long-term (>60 months) follow-up groups. INTERVENTION ESWL and ERCP. MAIN OUTCOME MEASUREMENTS Improvement in pain, analgesic use, hospitalization for pain, recurrence of calculi, need for additional intervention, and quality of life. RESULTS A total of 636 of 1006 patients who underwent ESWL between 2004 and 2009 were followed for a maximum of 96 months. There were 364 patients in the intermediate follow-up group and 272 in the long-term follow-up group. After ESWL and ERCP, absence of pain was seen in 250 patients (68.7%), mild-to-moderate pain in 94 patients (25.4%), and severe pain in 20 patients (5.5%) of the intermediate group. In the long-term group, 164 patients (60.3%) had no pain, 97 patients (35.7%) had mild or moderate episodes of pain, whereas 11 patients (4.04%) had episodic severe pain. Recurrence of calculi was seen in 51 patients (14.01%) in the intermediate follow-up group and in 62 patients (22.8%) in the long-term group. Quality of life improved in a significant number of patients in both groups. LIMITATIONS Retrospective study, single center, recall bias, and subjective pain and quality-of-life measurement scale. CONCLUSION ESWL for large PD calculi offers good results in patients of idiopathic CP on intermediate and long-term follow-up.", "author" : [ { "dropping-particle" : "", "family" : "Tandan", "given" : "Manu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reddy", "given" : "Duvvur Nageshwar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Talukdar", "given" : "Rupjyoti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vinod", "given" : "Koppuju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Santosh", "given" : "Darisetty", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lakhtakia", "given" : "Sundeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gupta", "given" : "Rajesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramchandani", "given" : "Mohan J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banerjee", "given" : "Rupa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rakesh", "given" : "Kalapala", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Varadaraj", "given" : "Gokak", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rao", "given" : "Guduru Venkat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gastrointestinal endoscopy", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2013", "11" ] ] }, "note" : "NULL", "page" : "726-33", "title" : "Long-term clinical outcomes of extracorporeal shockwave lithotripsy in painful chronic calcific pancreatitis.", "type" : "article-journal", "volume" : "78" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(275)", "plainTextFormattedCitation" : "(275)", "previouslyFormattedCitation" : "(275)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(275). Overall, these results point out that in well-selected cases, endoscopic interventions may result in around 60% complete pain relief rates in the subsequent five years after the intervention.However, there seems to be no consensus on the management of pain relapse in CP patients who underwent previous endoscopic interventions. In a retrospective study with 100 CP patients, only 38 (38%) of CP patients who had underwent endoscopic stenting required re-stenting within the 69-month follow-up period, and these patients were ultimately referred to surgery (pancreatico-jejuonstomy)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0013-726X", "PMID" : "18556820", "abstract" : "BACKGROUND AND STUDY AIMS Although it has been proved that pancreatic stenting is effective in the symptomatic management of severe chronic pancreatitis, long-term outcomes after stent removal have not been fully evaluated. PATIENTS AND METHODS A total of 100 patients (75 men, 25 women; median age 49) with severe chronic pancreatitis and pancreatic duct strictures were successfully treated for pancreatic pain using polyethylene pancreatic stents and were followed up for at least 1 year after stent removal. The stents were exchanged \"on demand\" (in cases of recurrence of pain) and a definitive stent removal was attempted on the basis of clinical and endoscopic findings. Clinical variables were retrospectively assessed as potential predictors of re-stenting. RESULTS The etiology of the chronic pancreatitis was alcoholic (77 %), idiopathic (18 %), or hereditary (5 %). Patients were followed up for a median period of 69 months (range 14 - 163 months) after study entry, including a median period of 27 months (range 12 - 126 months) after stent removal. The median duration of pancreatic stenting before stent removal was 23 months (range 2 - 134 months). After attempted definitive stent removal, 30 patients (30 %) required re-stenting within the first year of follow-up, at a median time of 5.5 months after stent removal (range 1 - 12 months), while in 70 patients (70 %) pain control remained adequate during that period. By the end of the follow-up period a total of 38 patients had required re-stenting and four ultimately underwent pancreaticojejunostomy. Pancreas divisum was the only factor significantly associated with a higher risk of re-stenting (P = 0.002). CONCLUSIONS The majority (70 %) of patients with severe chronic pancreatitis who respond to pancreatic stenting maintain this response after definitive stent removal. However, a significantly higher re-stenting rate was observed in patients with chronic pancreatitis and pancreas divisum.", "author" : [ { "dropping-particle" : "", "family" : "Eleftherladis", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dinu", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delhaye", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moine", "given" : "O", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baize", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vandermeeren", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hookey", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devi\u00e8re", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Endoscopy", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2005", "3" ] ] }, "note" : "NULL", "page" : "223-30", "title" : "Long-term outcome after pancreatic stenting in severe chronic pancreatitis.", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(239)", "plainTextFormattedCitation" : "(239)", "previouslyFormattedCitation" : "(239)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(239). In their retrospective series with 14 patients, Weber et al. had 6 patients who did not respond to endoscopic therapy, and 4 of these patients were treated using repeated stent therapy or analgesic/medical treatmentADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3748/wjg.v19.i5.715", "ISSN" : "2219-2840", "PMID" : "23430281", "abstract" : "AIM This study analyzed clinical long-term outcomes after endoscopic therapy, including the incidence and treatment of relapse. METHODS This study included 19 consecutive patients (12 male, 7 female, median age 54 years) with obstructive chronic pancreatitis who were admitted to the 2(nd) Medical Department of the Technical University of Munich. All patients presented severe chronic pancreatitis (stage III\u00b0) according to the Cambridge classification. The majority of the patients suffered intermittent pain attacks. 6 of 19 patients had strictures of the pancreatic duct; 13 of 19 patients had strictures and stones. The first endoscopic retrograde pancreatography (ERP) included an endoscopic sphincterotomy, dilatation of the pancreatic duct, and stent placement. The first control ERP was performed 4 wk after the initial intervention, and the subsequent control ERP was performed after 3 mo to re-evaluate the clinical and morphological conditions. Clinical follow-up was performed annually to document the course of pain and the management of relapse. The course of pain was assessed by a pain scale from 0 to 10. The date and choice of the therapeutic procedure were documented in case of relapse. RESULTS Initial endoscopic intervention was successfully completed in 17 of 19 patients. All 17 patients reported partial or complete pain relief after endoscopic intervention. Endoscopic therapy failed in 2 patients. Both patients were excluded from further analysis. One failed patient underwent surgery, and the other patient was treated conservatively with pain medication. Seventeen of 19 patients were followed after the successful completion of endoscopic stent therapy. Three of 17 patients were lost to follow-up. One patient was not available for interviews after the 1(st) year of follow-up. Two patients died during the 3(rd) year of follow-up. In both patients chronic pancreatitis was excluded as the cause of death. One patient died of myocardial infarction, and one patient succumbed to pneumonia. All three patients were excluded from follow-up analysis. Follow-up was successfully completed in 14 of 17 patients. 4 patients at time point 3, 2 patients at time point 4, 3 patients at time point 5 and 2 patients at time point 6 and time point 7 used continuous pain medication after endoscopic therapy. No relapse occurred in 57% (8/14) of patients. All 8 patients exhibited significantly reduced or no pain complaints during the 5-year follow-up. Seven of 8 patients were\u2026", "author" : [ { "dropping-particle" : "", "family" : "Weber", "given" : "Andreas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schneider", "given" : "Jochen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Neu", "given" : "Bruno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meining", "given" : "Alexander", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Born", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delius", "given" : "Stefan", "non-dropping-particle" : "von", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bajbouj", "given" : "Monther", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schmid", "given" : "Roland M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alg\u00fcl", "given" : "Hana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prinz", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "World journal of gastroenterology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2013", "2", "7" ] ] }, "note" : "NULL", "page" : "715-20", "title" : "Endoscopic stent therapy in patients with chronic pancreatitis: a 5-year follow-up study.", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(280)", "plainTextFormattedCitation" : "(280)", "previouslyFormattedCitation" : "(280)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(280). Only 2 of the 6 patients were referred to surgery. However, the rationale for the choice of three different strategies in these three pairs of patients was not delineated in the studyADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3748/wjg.v19.i5.715", "ISSN" : "2219-2840", "PMID" : "23430281", "abstract" : "AIM This study analyzed clinical long-term outcomes after endoscopic therapy, including the incidence and treatment of relapse. METHODS This study included 19 consecutive patients (12 male, 7 female, median age 54 years) with obstructive chronic pancreatitis who were admitted to the 2(nd) Medical Department of the Technical University of Munich. All patients presented severe chronic pancreatitis (stage III\u00b0) according to the Cambridge classification. The majority of the patients suffered intermittent pain attacks. 6 of 19 patients had strictures of the pancreatic duct; 13 of 19 patients had strictures and stones. The first endoscopic retrograde pancreatography (ERP) included an endoscopic sphincterotomy, dilatation of the pancreatic duct, and stent placement. The first control ERP was performed 4 wk after the initial intervention, and the subsequent control ERP was performed after 3 mo to re-evaluate the clinical and morphological conditions. Clinical follow-up was performed annually to document the course of pain and the management of relapse. The course of pain was assessed by a pain scale from 0 to 10. The date and choice of the therapeutic procedure were documented in case of relapse. RESULTS Initial endoscopic intervention was successfully completed in 17 of 19 patients. All 17 patients reported partial or complete pain relief after endoscopic intervention. Endoscopic therapy failed in 2 patients. Both patients were excluded from further analysis. One failed patient underwent surgery, and the other patient was treated conservatively with pain medication. Seventeen of 19 patients were followed after the successful completion of endoscopic stent therapy. Three of 17 patients were lost to follow-up. One patient was not available for interviews after the 1(st) year of follow-up. Two patients died during the 3(rd) year of follow-up. In both patients chronic pancreatitis was excluded as the cause of death. One patient died of myocardial infarction, and one patient succumbed to pneumonia. All three patients were excluded from follow-up analysis. Follow-up was successfully completed in 14 of 17 patients. 4 patients at time point 3, 2 patients at time point 4, 3 patients at time point 5 and 2 patients at time point 6 and time point 7 used continuous pain medication after endoscopic therapy. No relapse occurred in 57% (8/14) of patients. All 8 patients exhibited significantly reduced or no pain complaints during the 5-year follow-up. Seven of 8 patients were\u2026", "author" : [ { "dropping-particle" : "", "family" : "Weber", "given" : "Andreas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schneider", "given" : "Jochen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Neu", "given" : "Bruno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meining", "given" : "Alexander", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Born", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delius", "given" : "Stefan", "non-dropping-particle" : "von", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bajbouj", "given" : "Monther", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schmid", "given" : "Roland M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alg\u00fcl", "given" : "Hana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prinz", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "World journal of gastroenterology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2013", "2", "7" ] ] }, "note" : "NULL", "page" : "715-20", "title" : "Endoscopic stent therapy in patients with chronic pancreatitis: a 5-year follow-up study.", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(280)", "plainTextFormattedCitation" : "(280)", "previouslyFormattedCitation" : "(280)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(280). In a similar study, the investigators reported pain relapse in 5 out of 17 CP patients (stage III according to Cambridge classification) within the first two years after stent removal, and they speculated that repeated stenting may be an option for these relapse casesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/mpa.0b013e3180325ba6", "ISSN" : "1536-4828", "PMID" : "17414050", "abstract" : "OBJECTIVES Obstruction of the pancreatic duct is a common feature of chronic pancreatitis and often requires interventional therapy. The current prospective study investigated clinical success in 19 patients after initial endoscopic retrograde pancreaticography and relapse rates during a 2-year follow-up period. METHODS Seventeen of 19 patients with chronic pancreatitis (stage III according to the Cambridge classification) were treated by sphincterotomy and stent insertion. Endoscopic retrograde pancreaticography failed in 2 patients. RESULTS Strictures were cannulated, dilated, and stones were removed with a dormia basket in 13 of 17 patients. Extracorporeal shock wave lithotripsy was necessary in 5 patients. Polyethylene stents (7F-11.5F) were placed into the dilated pancreatic duct. Mean duration of internal pancreatic stenting was 5.6 months. Three of 17 patients had recurrence of pain during the first follow-up year after stent extraction; in the second follow-up year, another 2 patients had a relapse. Overall, patients' assessment of the stent therapy revealed complete satisfaction in 17 of 19 patients. CONCLUSIONS Endoscopic stent therapy is a safe, minimally invasive, and effective procedure in patients experiencing pain attacks during chronic pancreatitis associated with dilated pancreatic duct. According to our results, a relapse rate of approximately 30% can be expected within 2 years after stent extraction. These patients may be treated by repeated stent therapy.", "author" : [ { "dropping-particle" : "", "family" : "Weber", "given" : "Andreas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schneider", "given" : "Jochen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Neu", "given" : "Bruno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meining", "given" : "Alexander", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Born", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schmid", "given" : "Roland M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prinz", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pancreas", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2007", "4" ] ] }, "note" : "NULL", "page" : "287-94", "title" : "Endoscopic stent therapy for patients with chronic pancreatitis: results from a prospective follow-up study.", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(241)", "plainTextFormattedCitation" : "(241)", "previouslyFormattedCitation" : "(241)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(241). In a recent randomized, double blind, placebo-controlled trial, the 87 narcotic-na?ve CP patients with pain relapse after endoscopic ductal clearance received either antioxidant-pregabalin combination therapy (n=42) or matching placebo (n=45) for 2?months followed by open-label antioxidants for the next 4?months in both groupsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/jgh.13332", "ISSN" : "1440-1746", "PMID" : "26945817", "abstract" : "BACKGROUND AND AIM The aim of this study was to evaluate the effect of antioxidant-pregabalin combination on pain recurrence in patients with chronic calcific pancreatitis. METHODS In this randomized, double-blind, placebo-controlled trial, chronic calcific pancreatitis patients with pain recurrence following pancreatic ductal clearance of stones received either antioxidant-pregabalin combination or matching placebo for 2\u2009months followed by open-label antioxidants for the next 4\u2009months in both groups. Compliance, daily pain, and adverse events were recorded weekly and at the end of study by a coordinator blinded to treatment status. Primary outcome was pain improvement (visual analog scale and Izbicki score); secondary outcomes were as follows: complete pain resolution, painful days, and adverse events. Number needed-to-treat was calculated. RESULTS We randomized 42 and 45 patients (mean age 29.3\u2009years) to treatment and placebo arms, respectively. Baseline characteristics, including pain scores, were similar for both groups. No patients received high-potency narcotic. At 2\u2009months, a significant improvement in the treatment arm was observed in percent reduction of visual analog scale (-50 [-80.0; -32.1] vs -29.5 [-64.5; 0]; P\u2009=\u20090.01), Izbicki score (14.5 [0; 21.3] vs 30.0 [11.8; 41.3]; P\u2009=\u20090.001), complete pain resolution (20 [47.6%] vs 12 [26.7%]; P\u2009=\u20090.04), and number of painful days (10.0 [2.0; 16.0] vs 18.0 [7.0; 34.0]; P\u2009=\u20090.01). Needed-to-treat was 4.8. Pain reduction persisted at 6\u2009months in the original treatment group (20.0 [15.0; 28.0] vs 36.0 [20.0; 50.0]; P\u2009=\u20090.006). A total of 33 patients in the treatment arm experienced mild to moderate self-limiting nausea/vomiting and drowsiness, respectively and did not require any change in study protocol. CONCLUSION Antioxidant-pregabalin combination results in significant relief in pain recurrence after ductal clearance in narcotic na\u00efve patients with chronic calcific pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Talukdar", "given" : "Rupjyoti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lakhtakia", "given" : "Sundeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nageshwar Reddy", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rao", "given" : "G Venkat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pradeep", "given" : "Rebala", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banerjee", "given" : "Rupa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gupta", "given" : "Rajesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramchandani", "given" : "Mohan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tandan", "given" : "Manu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Murthy", "given" : "H Vivekananda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of gastroenterology and hepatology", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2016", "9" ] ] }, "page" : "1654-62", "title" : "Ameliorating effect of antioxidants and pregabalin combination in pain recurrence after ductal clearance in chronic pancreatitis: Results of a randomized, double blind, placebo-controlled trial.", "type" : "article-journal", "volume" : "31" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(192)", "plainTextFormattedCitation" : "(192)", "previouslyFormattedCitation" : "(192)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(192). In the treatment arm, the combined antioxidant-pregabalin therapy resulted in reduced pain scores, higher frequency of pain resolution, and reduced number of painful days when compared to placeboADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/jgh.13332", "ISSN" : "1440-1746", "PMID" : "26945817", "abstract" : "BACKGROUND AND AIM The aim of this study was to evaluate the effect of antioxidant-pregabalin combination on pain recurrence in patients with chronic calcific pancreatitis. METHODS In this randomized, double-blind, placebo-controlled trial, chronic calcific pancreatitis patients with pain recurrence following pancreatic ductal clearance of stones received either antioxidant-pregabalin combination or matching placebo for 2\u2009months followed by open-label antioxidants for the next 4\u2009months in both groups. Compliance, daily pain, and adverse events were recorded weekly and at the end of study by a coordinator blinded to treatment status. Primary outcome was pain improvement (visual analog scale and Izbicki score); secondary outcomes were as follows: complete pain resolution, painful days, and adverse events. Number needed-to-treat was calculated. RESULTS We randomized 42 and 45 patients (mean age 29.3\u2009years) to treatment and placebo arms, respectively. Baseline characteristics, including pain scores, were similar for both groups. No patients received high-potency narcotic. At 2\u2009months, a significant improvement in the treatment arm was observed in percent reduction of visual analog scale (-50 [-80.0; -32.1] vs -29.5 [-64.5; 0]; P\u2009=\u20090.01), Izbicki score (14.5 [0; 21.3] vs 30.0 [11.8; 41.3]; P\u2009=\u20090.001), complete pain resolution (20 [47.6%] vs 12 [26.7%]; P\u2009=\u20090.04), and number of painful days (10.0 [2.0; 16.0] vs 18.0 [7.0; 34.0]; P\u2009=\u20090.01). Needed-to-treat was 4.8. Pain reduction persisted at 6\u2009months in the original treatment group (20.0 [15.0; 28.0] vs 36.0 [20.0; 50.0]; P\u2009=\u20090.006). A total of 33 patients in the treatment arm experienced mild to moderate self-limiting nausea/vomiting and drowsiness, respectively and did not require any change in study protocol. CONCLUSION Antioxidant-pregabalin combination results in significant relief in pain recurrence after ductal clearance in narcotic na\u00efve patients with chronic calcific pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Talukdar", "given" : "Rupjyoti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lakhtakia", "given" : "Sundeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nageshwar Reddy", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rao", "given" : "G Venkat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pradeep", "given" : "Rebala", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banerjee", "given" : "Rupa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gupta", "given" : "Rajesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramchandani", "given" : "Mohan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tandan", "given" : "Manu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Murthy", "given" : "H Vivekananda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of gastroenterology and hepatology", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2016", "9" ] ] }, "page" : "1654-62", "title" : "Ameliorating effect of antioxidants and pregabalin combination in pain recurrence after ductal clearance in chronic pancreatitis: Results of a randomized, double blind, placebo-controlled trial.", "type" : "article-journal", "volume" : "31" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(192)", "plainTextFormattedCitation" : "(192)", "previouslyFormattedCitation" : "(192)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(192). The pain reduction was further persistent at 6 months in the treatment groupADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/jgh.13332", "ISSN" : "1440-1746", "PMID" : "26945817", "abstract" : "BACKGROUND AND AIM The aim of this study was to evaluate the effect of antioxidant-pregabalin combination on pain recurrence in patients with chronic calcific pancreatitis. METHODS In this randomized, double-blind, placebo-controlled trial, chronic calcific pancreatitis patients with pain recurrence following pancreatic ductal clearance of stones received either antioxidant-pregabalin combination or matching placebo for 2\u2009months followed by open-label antioxidants for the next 4\u2009months in both groups. Compliance, daily pain, and adverse events were recorded weekly and at the end of study by a coordinator blinded to treatment status. Primary outcome was pain improvement (visual analog scale and Izbicki score); secondary outcomes were as follows: complete pain resolution, painful days, and adverse events. Number needed-to-treat was calculated. RESULTS We randomized 42 and 45 patients (mean age 29.3\u2009years) to treatment and placebo arms, respectively. Baseline characteristics, including pain scores, were similar for both groups. No patients received high-potency narcotic. At 2\u2009months, a significant improvement in the treatment arm was observed in percent reduction of visual analog scale (-50 [-80.0; -32.1] vs -29.5 [-64.5; 0]; P\u2009=\u20090.01), Izbicki score (14.5 [0; 21.3] vs 30.0 [11.8; 41.3]; P\u2009=\u20090.001), complete pain resolution (20 [47.6%] vs 12 [26.7%]; P\u2009=\u20090.04), and number of painful days (10.0 [2.0; 16.0] vs 18.0 [7.0; 34.0]; P\u2009=\u20090.01). Needed-to-treat was 4.8. Pain reduction persisted at 6\u2009months in the original treatment group (20.0 [15.0; 28.0] vs 36.0 [20.0; 50.0]; P\u2009=\u20090.006). A total of 33 patients in the treatment arm experienced mild to moderate self-limiting nausea/vomiting and drowsiness, respectively and did not require any change in study protocol. CONCLUSION Antioxidant-pregabalin combination results in significant relief in pain recurrence after ductal clearance in narcotic na\u00efve patients with chronic calcific pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Talukdar", "given" : "Rupjyoti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lakhtakia", "given" : "Sundeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nageshwar Reddy", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rao", "given" : "G Venkat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pradeep", "given" : "Rebala", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banerjee", "given" : "Rupa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gupta", "given" : "Rajesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramchandani", "given" : "Mohan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tandan", "given" : "Manu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Murthy", "given" : "H Vivekananda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of gastroenterology and hepatology", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2016", "9" ] ] }, "page" : "1654-62", "title" : "Ameliorating effect of antioxidants and pregabalin combination in pain recurrence after ductal clearance in chronic pancreatitis: Results of a randomized, double blind, placebo-controlled trial.", "type" : "article-journal", "volume" : "31" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(192)", "plainTextFormattedCitation" : "(192)", "previouslyFormattedCitation" : "(192)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(192). Therefore, after endoscopic interventions, the evidence for recommending a certain type of therapy for pain relapse is yet quite immature. However, it seems that endoscopy may provide adequate pain relief in selected cases, and patients with pain relapse may benefit from few additional sessions of repeat interventions like stenting, or subsequent medical treatment via antioxidants together with pregabalin. The caveat behind these observations is that all these studies with pain relapse after endoscopy did not include a study arm of patients who were referred to surgery after pain relapse. In fact, previous endoscopic stenting was not identified to be a risk factor for more or recurrent pain after surgery (pancreatico-jejunostomy)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/11024150260102834", "ISSN" : "1102-4151", "PMID" : "12440760", "abstract" : "OBJECTIVE To assess whether previous endoscopic stenting of the pancreatic duct influences the outcome of subsequent pancreaticojejunostomy in chronic pancreatitis. DESIGN Retrospective analysis. SETTING University hospital, the Netherlands. PATIENTS 50 patients with chronic pancreatitis, 26 of whom had previously had stents inserted and 24 who had not. INTERVENTIONS A questionnaire was sent to each patient to evaluate long-term pain relief, readmissions during follow-up and subjective efficacy of the operation, and risk factors for recurrent pain were calculated. MAIN OUTCOME MEASURES Postoperative morbidity, pain relief and subjective efficacy. RESULTS Patients with stents were operated on later (after 60 months of symptoms) than those without (17 months). 5 (19%) and 2 (8%) patients developed complications. No patient died. Personal follow-up (median 27 months) was obtained in 41 of 44 available patients (93%). 36 patients (88%) felt that they had benefited from pancreaticojejunostomy. 13 of the 21 patients with stents (62%) and 11 of the 20 patients without stents (55%) reported pain at least monthly, but of these 24 patients 21 patients (88%) had less pain than preoperatively; 11 (22%) had pain daily. 13 patients were readmitted for a relapse of pancreatitis, 3 of whom required partial pancreatectomy. Previous endoscopic stenting of the pancreatic duct was not a risk factor for recurrent pain (p = 0.61). CONCLUSION Endoscopic stenting of the pancreatic duct may be done for patients with chronic pancreatitis without adverse effects on the outcome of subsequent pancreaticojejunostomy.", "author" : [ { "dropping-particle" : "", "family" : "Boerma", "given" : "Djemila", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gulik", "given" : "Thomas M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rauws", "given" : "Erik A J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Obertop", "given" : "Huug", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gouma", "given" : "Dirk J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The European journal of surgery = Acta chirurgica", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2002", "7", "1" ] ] }, "note" : "NULL", "page" : "223-8", "title" : "Outcome of pancreaticojejunostomy after previous endoscopic stenting in patients with chronic pancreatitis.", "type" : "article-journal", "volume" : "168" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(350)", "plainTextFormattedCitation" : "(350)", "previouslyFormattedCitation" : "(350)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(350).Lack of sufficient evidence for concrete recommendations for managing pain relapse in CP also holds true for the post-surgery pain relapse. In a series with 39 patients who developed pain relapse after surgery (resection or drainage operation) from a pool of 316 patients, Howard et al. found that revision of pancreatico-jejunostomy enabled pain relief in 67% of the patients, whereas partial resections such as duodenum-preserving pancreatic head resection, pancreaticoduodenectomy, or distal pancreatectomy achieved pain relief in <50% of the patientsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s11605-008-0713-6", "ISSN" : "1873-4626", "PMID" : "18846404", "abstract" : "INTRODUCTION Resection and drainage operations achieve long-term pain relief in approximately 85% of patients with chronic pancreatitis (CP). In patients who develop recurrent pain, a few data exist on the long-term results of remedial operations. MATERIALS AND METHODS Over an 18-year period (1988-2006), 316 patients with CP had primary resection or drainage operations at our institution. Thirty-nine developed recurrent pain and were treated by a remedial resection or drainage operation. Patient demographics, time to symptom recurrence, radiographic anatomic abnormalities, type of remedial operation, postoperative morbidity, and long-term outcomes were analyzed. RESULTS Thirty-nine patients, 56% female with a mean age of 41 years (range 16-61 years) had either remedial resection: total pancreatectomy (TP; N = 8), pancreaticoduodenectomy (PD; N = 6), distal pancreatectomy (DP; N = 5), or drainage operation: duodenal preserving pancreatic head resection (DPPHR; N = 8), revision of pancreaticojejunostomy (N = 12). TP achieved pain relief in 88% with postoperative complications greater than or equal to grade III in 38% and diabetes in 100%. Drainage operations achieved pain relief in 67% of patients with postoperative complications greater than or equal to grade III in only 8%. Partial parenchymal resections (DPPHR, PD, DP) as a remedial procedure achieved pain relief <50% of the time. CONCLUSION Drainage procedures, when anatomically feasible, are the preferred reoperation to treat patients with recurrent pain after failed primary operation for chronic pancreatitis.", "author" : [ { "dropping-particle" : "", "family" : "Howard", "given" : "Thomas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Browne", "given" : "Jeffrey S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zyromski", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lavu", "given" : "Harish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baker", "given" : "Marshall S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shen", "given" : "Changyu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Madura", "given" : "James A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2008", "12", "10" ] ] }, "note" : "NULL", "page" : "2087-95; discussion 2095-6", "title" : "Mechanisms of primary operative failure and results of remedial operation in patients with chronic pancreatitis.", "type" : "article-journal", "volume" : "12" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(351)", "plainTextFormattedCitation" : "(351)", "previouslyFormattedCitation" : "(351)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(351). In a long-term follow-up series (10-year follow-up), Talamini et al. also identified pancreatico-jejunostomy to significantly correlate to a smaller annual number of pain relapsesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0002-9610", "PMID" : "8678201", "abstract" : "PURPOSE To evaluate whether the annual number of pain relapses of chronic pancreatitis correlated with sex, type of pancreatitis, drinking and smoking, presence of intraductal calcifications, pancreaticojejunostomy, and length of follow-up in the first 10 years of follow-up. METHODS The authors analyzed 205 nonobstructive chronic pancreatitis cases with at least a 10 year follow-up, for a total of 2,034 person/year observations. Data were recorded on the daily number of cigarettes smoked and grams of alcohol drunk, as well as the presence of intraductal calcifications, and performance of pancreaticojejunostomy. RESULTS The model for multivariate autoregressive repeated measures analysis indicated that drinking (P < 0.0001), smoking (P < 0.0001), calcifications (P < 0.0001), pancreaticojejunostomy (P < 0.0011), and length of follow-up (P < 0.0001) all correlated significantly with annual number of pain relapses. Pancreaticojejunostomy is probably very effective in reducing pain both physically, by removing the largest intraductal calcifications and obstructions through drainage of Wirsung's duct, and psychologically, by inducing patients to cut down their postsurgical alcohol intake. CONCLUSIONS Regardless of surgical treatment, patients should be advised to reduce both their alcohol intake and cigarette smoking.", "author" : [ { "dropping-particle" : "", "family" : "Talamini", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bassi", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Falconi", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sartori", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salvia", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Francesco", "given" : "V", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frulloni", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vaona", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bovo", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vantini", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pederzoli", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cavallini", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American journal of surgery", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "1996", "6" ] ] }, "note" : "NULL", "page" : "565-9", "title" : "Pain relapses in the first 10 years of chronic pancreatitis.", "type" : "article-journal", "volume" : "171" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(352)", "plainTextFormattedCitation" : "(352)", "previouslyFormattedCitation" : "(352)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(352). In another case series, Markowitz et al. performed different types of salvage operations on 13 CP patients who previously had pancreatico-jejunostomyADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0004-0010", "PMID" : "8154964", "abstract" : "OBJECTIVE To evaluate causes of intractable recurrent pain following pancreaticojejunostomy for chronic pancreatitis and to evaluate treatment strategies aimed at lasting pain relief. DESIGN Case series. SETTING Tertiary care referral center. PATIENTS Fifteen selected patients having severe pain associated with chronic pancreatitis with onset 0 to 60 months (median, 5 months) following pancreaticojejunostomy. Each patient underwent computed tomography and endoscopic retrograde cholangiopancreatography. Two patients (13%) were found to have pancreatic cancer, two (13%) had inadequate pancreatic duct decompression, two (13%) had biliary stenosis, and 10 (67%) had presumed neuropathy in the pancreatic head. INTERVENTIONS Fourteen (93%) of the 15 patients underwent the following reoperations: distal pancreatectomy and splenectomy (one patient), extension of the pancreaticojejunostomy and choledochojejunostomy (one patient), biliary stenting followed by choledochojejunostomy (one patient), and Whipple-type resection of the pancreatic head (14 patients). Two patients subsequently underwent a completion pancreatectomy. MAIN OUTCOME MEASURES Pain relief, functional capacity, and pancreatic exocrine and endocrine status were determined. The median follow-up after reoperation was 39 months. RESULTS Of the 14 patients who underwent reoperation, 13 were long-term survivors. One died of pancreatic cancer. Ten of the other 13 have had satisfactory-to-excellent relief of pain, with resumption of a normal level of function. Of the 10 previously euglycemic patients who underwent pancreatic head resection, eight remain free of diabetes mellitus to date. CONCLUSIONS The causes of recurrent or persistent pain following pancreaticojejunal decompression for chronic pancreatitis are complex and include neuropathic changes, residual or evolving pancreatic and biliary duct obstruction, and unrecognized pancreatic cancer. Acceptable outcomes can usually be achieved by following a treatment strategy aimed at addressing identified residual disease while maximally preserving pancreatic tissue.", "author" : [ { "dropping-particle" : "", "family" : "Markowitz", "given" : "J S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rattner", "given" : "D W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Warshaw", "given" : "A L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Archives of surgery (Chicago, Ill. : 1960)", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "1994", "4" ] ] }, "note" : "NULL", "page" : "374-9; discussion 379-80", "title" : "Failure of symptomatic relief after pancreaticojejunal decompression for chronic pancreatitis. Strategies for salvage.", "type" : "article-journal", "volume" : "129" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(353)", "plainTextFormattedCitation" : "(353)", "previouslyFormattedCitation" : "(353)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(353). These operations included distal pancreatectomy, extension of the pancreaticojejunostomy and choledochojejunostomy, biliary stenting followed by choledochojejunostomy, and pancreatico-duodenectomyADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0004-0010", "PMID" : "8154964", "abstract" : "OBJECTIVE To evaluate causes of intractable recurrent pain following pancreaticojejunostomy for chronic pancreatitis and to evaluate treatment strategies aimed at lasting pain relief. DESIGN Case series. SETTING Tertiary care referral center. PATIENTS Fifteen selected patients having severe pain associated with chronic pancreatitis with onset 0 to 60 months (median, 5 months) following pancreaticojejunostomy. Each patient underwent computed tomography and endoscopic retrograde cholangiopancreatography. Two patients (13%) were found to have pancreatic cancer, two (13%) had inadequate pancreatic duct decompression, two (13%) had biliary stenosis, and 10 (67%) had presumed neuropathy in the pancreatic head. INTERVENTIONS Fourteen (93%) of the 15 patients underwent the following reoperations: distal pancreatectomy and splenectomy (one patient), extension of the pancreaticojejunostomy and choledochojejunostomy (one patient), biliary stenting followed by choledochojejunostomy (one patient), and Whipple-type resection of the pancreatic head (14 patients). Two patients subsequently underwent a completion pancreatectomy. MAIN OUTCOME MEASURES Pain relief, functional capacity, and pancreatic exocrine and endocrine status were determined. The median follow-up after reoperation was 39 months. RESULTS Of the 14 patients who underwent reoperation, 13 were long-term survivors. One died of pancreatic cancer. Ten of the other 13 have had satisfactory-to-excellent relief of pain, with resumption of a normal level of function. Of the 10 previously euglycemic patients who underwent pancreatic head resection, eight remain free of diabetes mellitus to date. CONCLUSIONS The causes of recurrent or persistent pain following pancreaticojejunal decompression for chronic pancreatitis are complex and include neuropathic changes, residual or evolving pancreatic and biliary duct obstruction, and unrecognized pancreatic cancer. Acceptable outcomes can usually be achieved by following a treatment strategy aimed at addressing identified residual disease while maximally preserving pancreatic tissue.", "author" : [ { "dropping-particle" : "", "family" : "Markowitz", "given" : "J S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rattner", "given" : "D W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Warshaw", "given" : "A L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Archives of surgery (Chicago, Ill. : 1960)", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "1994", "4" ] ] }, "note" : "NULL", "page" : "374-9; discussion 379-80", "title" : "Failure of symptomatic relief after pancreaticojejunal decompression for chronic pancreatitis. Strategies for salvage.", "type" : "article-journal", "volume" : "129" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(353)", "plainTextFormattedCitation" : "(353)", "previouslyFormattedCitation" : "(353)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(353). Ten of the 13 patients experience considerable or even excellent pain relief ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0004-0010", "PMID" : "8154964", "abstract" : "OBJECTIVE To evaluate causes of intractable recurrent pain following pancreaticojejunostomy for chronic pancreatitis and to evaluate treatment strategies aimed at lasting pain relief. DESIGN Case series. SETTING Tertiary care referral center. PATIENTS Fifteen selected patients having severe pain associated with chronic pancreatitis with onset 0 to 60 months (median, 5 months) following pancreaticojejunostomy. Each patient underwent computed tomography and endoscopic retrograde cholangiopancreatography. Two patients (13%) were found to have pancreatic cancer, two (13%) had inadequate pancreatic duct decompression, two (13%) had biliary stenosis, and 10 (67%) had presumed neuropathy in the pancreatic head. INTERVENTIONS Fourteen (93%) of the 15 patients underwent the following reoperations: distal pancreatectomy and splenectomy (one patient), extension of the pancreaticojejunostomy and choledochojejunostomy (one patient), biliary stenting followed by choledochojejunostomy (one patient), and Whipple-type resection of the pancreatic head (14 patients). Two patients subsequently underwent a completion pancreatectomy. MAIN OUTCOME MEASURES Pain relief, functional capacity, and pancreatic exocrine and endocrine status were determined. The median follow-up after reoperation was 39 months. RESULTS Of the 14 patients who underwent reoperation, 13 were long-term survivors. One died of pancreatic cancer. Ten of the other 13 have had satisfactory-to-excellent relief of pain, with resumption of a normal level of function. Of the 10 previously euglycemic patients who underwent pancreatic head resection, eight remain free of diabetes mellitus to date. CONCLUSIONS The causes of recurrent or persistent pain following pancreaticojejunal decompression for chronic pancreatitis are complex and include neuropathic changes, residual or evolving pancreatic and biliary duct obstruction, and unrecognized pancreatic cancer. Acceptable outcomes can usually be achieved by following a treatment strategy aimed at addressing identified residual disease while maximally preserving pancreatic tissue.", "author" : [ { "dropping-particle" : "", "family" : "Markowitz", "given" : "J S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rattner", "given" : "D W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Warshaw", "given" : "A L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Archives of surgery (Chicago, Ill. : 1960)", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "1994", "4" ] ] }, "note" : "NULL", "page" : "374-9; discussion 379-80", "title" : "Failure of symptomatic relief after pancreaticojejunal decompression for chronic pancreatitis. Strategies for salvage.", "type" : "article-journal", "volume" : "129" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(353)", "plainTextFormattedCitation" : "(353)", "previouslyFormattedCitation" : "(353)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(353). Hence, the type of surgery to be chosen for a re-operation on a CP patient with relapse may vary, depending on the pancreatic morphology. In all cases, it is crucial to first exclude more simple reasons for therapy failure such as obvious stricture of anastomosis, or obstructing stones in the pancreatic or bile ductADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0364-2313", "PMID" : "2407041", "abstract" : "The management of any patient with recurrent pain following surgery for chronic pancreatitis is far from an easy problem. Even more careful assessment than that preceding the decision for the first operation will be necessary. In-hospital patient assessment is strongly recommended to ascertain the degree of the problem of pain in as objective a manner as possible. The effects of alcohol withdrawal and different analgesic treatments have to be carefully assessed while obtaining essential information on the size and shape of the pancreatic duct as well as the general pancreatic morphology. Relatively simple procedures such as the removal of stones or the enlargement of a strictured anastomosis may be all that is required to ensure freedom from pain; however, there is a tendency for patients who have no obvious new pathology or simple failure of the first operation to move to more extensive resectional procedures. This, ultimately will lead to total pancreatectomy being recommended and long-term follow-up of such patients is under critical scrutiny. Unless the highest caliber of support services can be mustered for these patients subject to total pancreatectomy, the morbidity and mortality in the longer term can reach prohibitive levels. A plea is made for objective reassessment of the place of celiac ganglionectomy in the management of these difficult problems.", "author" : [ { "dropping-particle" : "", "family" : "Imrie", "given" : "C W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "World journal of surgery", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "0" ] ] }, "note" : "NULL", "page" : "88-93", "title" : "Management of recurrent pain following previous surgery for chronic pancreatitis.", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(354)", "plainTextFormattedCitation" : "(354)", "previouslyFormattedCitation" : "(354)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(354), that can possibly be removed by endotherapy interventions. Furthermore, it should be considered that a salvage operation for pain relapse may end up in a total pancreatectomy, which, in patients with predictably low postoperative compliance, would impose a major problem due to the unavoidable postoperative diabetes mellitus. In patients with pain relapse after pancreatic surgery, surgeons should consider that any kind of subsequent treatment may be subject to failure due to the intra- and extrapancreatic neuropathic alterations that may be irreversibleADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/gut.2007.146621", "ISSN" : "1468-3288", "PMID" : "18566105", "abstract" : "Pain mechanisms in patients with chronic pancreatitis are incompletely understood and probably multifactorial. Recently, evidence from experimental human pain research has indicated that in many of these patients pain processing in the central nervous system is abnormal and mimics that seen in neuropathic pain disorders. The current review focuses on several lines of evidence supporting this hypothesis. Hence, the spontaneous and postprandial pain in chronic pancreatitis may reflect the characteristic pain features seen in patients with neuropathic pain. Biochemical and histopathological findings in tissues from patients with chronic pancreatitis are similar to those observed in patients with other nerve fibre lesions. Experimental studies have shown that patients with chronic pancreatitis show signs of spinal hyper-excitability counter-balanced by segmental and descending inhibition. Changes in the brain with cortical reorganisation to gut stimulation and increased activity in specific electroencephalographic features characteristic for neuropathic pain are also seen in patients with chronic pancreatitis. Finally, principles involved in the treatment of pancreatic pain have many similarities with those recommended in neuropathic pain disorders. In conclusion, a mechanism-based understanding of pain in chronic pancreatitis may have important implications for the treatment.", "author" : [ { "dropping-particle" : "", "family" : "Drewes", "given" : "A M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Krarup", "given" : "A L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Detlefsen", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Malmstr\u00f8m", "given" : "M-L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dimcevski", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Funch-Jensen", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gut", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2008", "11", "1" ] ] }, "note" : "NULL", "page" : "1616-27", "title" : "Pain in chronic pancreatitis: the role of neuropathic pain mechanisms.", "type" : "article-journal", "volume" : "57" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(202)", "plainTextFormattedCitation" : "(202)", "previouslyFormattedCitation" : "(202)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(202)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00423-010-0731-1", "ISSN" : "1435-2451", "PMID" : "21153480", "abstract" : "BACKGROUND Unraveling the mechanisms of pain in chronic pancreatitis (CP) remains a true challenge. The rapid development of pancreatic surgery in the twentieth century, usage of advanced molecular biological techniques, and emergence of clinician-scientists have enabled the elucidation of several mechanisms that lead to the chronic, complicated neuropathic pain syndrome in CP. However, the proper analysis of pain in CP should include three main arms of mechanisms: \"peripheral nociception,\" \"peripheral/pancreatic neuropathy and neuroplasticity,\" and \"central neuropathy and neuroplasticity.\" DISCUSSION According to our current knowledge, pain in CP involves sustained sensitization of pancreatic peripheral nociceptors by neurotransmitters and neurotrophic factors following neural damage. This peripheral pancreatic neuropathy leads to intrapancreatic neuroplastic alterations that involve a profound switch in the autonomic innervation of the human pancreas via \"neural remodeling.\" Furthermore, this neuropathy entails a hyperexcitability of spinal sensory second-order neurons, which are subject to modulation from the brainstem via descending facilitation. Finally, viscerosensory cortical areas react to this central sensitization via spatial reorganization and thus a central neuroplasticity. The present review summarizes the current findings in these arms of mechanisms and introduces a novel concept to consistently describe pain in CP as a \"predominantly neuropathic,\" \"mixed-type\" pain.", "author" : [ { "dropping-particle" : "", "family" : "Demir", "given" : "Ihsan Ekin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tieftrunk", "given" : "Elke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maak", "given" : "Matthias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Friess", "given" : "Helmut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ceyhan", "given" : "G\u00fcralp Onur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Langenbeck's archives of surgery", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2011", "2", "10" ] ] }, "note" : "NULL", "page" : "151-60", "title" : "Pain mechanisms in chronic pancreatitis: of a master and his fire.", "type" : "article-journal", "volume" : "396" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(355)", "plainTextFormattedCitation" : "(355)", "previouslyFormattedCitation" : "(355)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(355). In any case, relapse-free intervals were reported to be longer after surgery for CP when compared to endoscopic treatmentADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00268-010-0713-z", "ISSN" : "1432-2323", "PMID" : "20645098", "abstract" : "OBJECTIVE Patients with chronic pancreatitis usually have a long and debilitating history of disease with frequent hospital admissions, episodes of intractable pain and multiple interventions. The sequences of treatment at initial presentation, endoscopy, surgery, or conservative treatment may affect the time course and admissions needed for disease control, thereby determining quality of life and overall outcome. METHODS A total of 292 patients with initial endoscopic, surgical, or conservative pharmacological treatment were retrospectively analyzed regarding frequency of interventions, days in hospital, symptom-free intervals, morbidity, and mortality. Quality of life (QoL) at the latest follow-up was measured by two standardized quality of life questionnaires (EORTC C30 and PAN26). RESULTS Endoscopic treatment was initially performed in 150 (51.4%) patients, whereas 99 (33.9%) underwent surgery and 43 (14.7%) patients were treated conservatively at their initial presentation. Patients who underwent surgery had a significantly shorter time in the hospital (25.3\u00a0\u00b1\u00a024.6, 34.4\u00a0\u00b1\u00a035.1, 61.1\u00a0\u00b1\u00a037.9; P\u00a0<\u00a00.001), fewer subsequent therapies (0.43\u00a0\u00b1\u00a01.0, 2.1\u00a0\u00b1\u00a02.4, 3.1\u00a0\u00b1\u00a03.0; P\u00a0\u2264\u00a00.001), and a longer relapse-free interval (P\u00a0=\u00a00.004) compared with endoscopically treated patients. The overall complication rate was 32% both after surgery and endoscopy. Infectious-related complications occurred more often after surgical treatment (P\u00a0\u2264\u00a00.001), whereas patients after endoscopic intervention developed acute or chronic pancreatitis or pseudocyst formation (P\u00a0=\u00a00.023). CONCLUSIONS Patients who undergo surgery as their initial treatment for chronic pancreatitis require less consecutive interventions, a shorter hospital stay, and have a better quality of life compared with any other treatment. Surgery should therefore be considered early for the treatment of chronic pancreatitis, when endoscopic or conservative treatment fails and patients require further intervention.", "author" : [ { "dropping-particle" : "", "family" : "Rutter", "given" : "Karoline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferlitsch", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sautner", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "P\u00fcsp\u00f6k", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "G\u00f6tzinger", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gangl", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schindl", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "World journal of surgery", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2010", "11", "20" ] ] }, "page" : "2642-7", "title" : "Hospitalization, frequency of interventions, and quality of life after endoscopic, surgical, or conservative treatment in patients with chronic pancreatitis.", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(279)", "plainTextFormattedCitation" : "(279)", "previouslyFormattedCitation" : "(279)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(279). In conclusion, pain relapse after surgical or endoscopic treatment of CP is a frequent and clinically very relevant problem. Current evidence suggests that the first step for the management of pain relapse should be exclusion of obstructing stones or strictured anastomosis via imaging, followed by a limited number endoscopic interventions, and early consideration of re-surgery to achieve pain control. This should be supported by an adequate pain therapy (see pharmacological pain treatment section), figure 5. Studies that address the management of pain relapse after surgery for CP, and that contain endoscopic and surgical intervention arms in a randomized, controlled setting are eagerly awaited.57150012763500114300-512445Figure 5: Management of pain relapse in chronic pancreatitis after surgery or endoscopy. Even after surgery for CP (e.g. duodenum-preserving pancreatic head resection or drainage operations), repeat surgery can be a viable and effective option to treat pain relapse. Prior to surgery, though, obstructing stones or anastomotic strictures should be evaluated on imaging and interdisciplinarily whether they can be addressed in an endoscopic intervention. Salvage surgery for pain relapse in CP can in most cases be organ-sparing. In cases where organ-sparing procedures are not possible, total pancreatectomy can be effective option, yet at the cost of postoperative diabetes.00Figure 5: Management of pain relapse in chronic pancreatitis after surgery or endoscopy. Even after surgery for CP (e.g. duodenum-preserving pancreatic head resection or drainage operations), repeat surgery can be a viable and effective option to treat pain relapse. Prior to surgery, though, obstructing stones or anastomotic strictures should be evaluated on imaging and interdisciplinarily whether they can be addressed in an endoscopic intervention. Salvage surgery for pain relapse in CP can in most cases be organ-sparing. In cases where organ-sparing procedures are not possible, total pancreatectomy can be effective option, yet at the cost of postoperative diabetes.Christopher Halloran and Dhiraj YadavQ13. What are the indications for referral to a specialist centre for further investigation of pain?All patients with presumed or established diagnoses of CP should be routinely referred to specialist pancreatic centers for investigation and treatment of their pain (quality assessment moderate; Recommendation: strong; Agreement: strong).Treatment of CP is challenging. It is vital that a systematic and robust approach is employed. Patients with pain from presumed CP require stepwise evaluation. Many patients are not referred in a timely fashion to specialist pancreatic or pain services until their pain progressively worsens or has become recalcitrant. The only evidence for benefit of referral comes from “general” advice regarding referral to chronic pain service’s:Referral should be considered when non-specialist management is failing, chronic pain is poorly controlled, there is significant distress, and/or where specific specialist intervention or assessment is considered. A systematic review of observational studies concluded that longer delays between specialist referral and specialist consultation result in poorer health and pain management by the time of this consultation. This deterioration starts as early as five weeks from referral and there is consensus that a delay of longer than six months is medically unacceptableADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.pain.2007.06.018", "ISSN" : "1872-6623", "PMID" : "17707589", "abstract" : "In many countries timely access to care is a growing problem. As medical costs escalate health care resources must be prioritized. In this context there is an increasing need for benchmarks and best practices in wait-time management. The Canadian Pain Society struck a Task Force in December 2005 to identify benchmarks for acceptable wait-times for treatment of chronic pain. As part of the mandate a systematic review of the literature regarding the relationship between waiting times, health status and health outcomes for patients awaiting treatment for chronic pain was undertaken. Twenty-four studies met the inclusion criteria for the review. The current review supports that patients experience a significant deterioration in health related quality of life and psychological well being while waiting for treatment for chronic pain during the 6 months from the time of referral to treatment. It is unknown at what point this deterioration begins as results from the 14 trials involving wait-times of 10 weeks or less yielded mixed results with wait-times amounting to as little as 5 weeks, associated with deterioration. It was concluded that wait-times for chronic pain treatment of 6 months or longer are medically unacceptable. Further study is necessary to determine at what stage the deterioration begins from the onset of pain to treatment and the impact of waiting on treatment outcomes. Most important is the need to improve access to appropriate care for patients with chronic pain, an escalating public health care problem with significant human and economic costs.", "author" : [ { "dropping-particle" : "", "family" : "Lynch", "given" : "Mary E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Campbell", "given" : "Fiona", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clark", "given" : "Alexander J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dunbar", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goldstein", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peng", "given" : "Philip", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stinson", "given" : "Jennifer", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tupper", "given" : "Helen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pain", "id" : "ITEM-1", "issue" : "1-2", "issued" : { "date-parts" : [ [ "2008", "5" ] ] }, "note" : "NULL", "page" : "97-116", "title" : "A systematic review of the effect of waiting for treatment for chronic pain.", "type" : "article-journal", "volume" : "136" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "(356)", "plainTextFormattedCitation" : "(356)", "previouslyFormattedCitation" : "(356)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(356).No RCT evidence was found that early or late initiation of specific treatments or early or late specialist referral influences outcome in patients with chronic pain.It should be considered whether patients with presumed or established diagnoses of chronic pancreatitis should be referred to specialist pancreatic centers not only for metabolic management, but also for assessment of type of pain (neuropathic/nociceptive/mixed), severity, functional impact and context. This includes not only assessment of chronic pancreatic pain vs. chronic non-pancreatic abdominal pain, but also the requirement in such patients to assess their overall pancreatic disease and to make appropriate management plans. Most importantly to diagnose whether:Primary pancreatic pathology is responsible for the plications of chronic pancreatitis are responsible for the pain.Differentiate between a treatable pancreatic conditions as cause of the pain vs. a chronic pain syndrome without pancreatic disease vs. an alternate diagnosis.ReferencesADDIN Mendeley Bibliography CSL_BIBLIOGRAPHY 1. Yadav D, Lowenfels AB. The Epidemiology of Pancreatitis and Pancreatic Cancer. Gastroenterology [Internet]. 2013 May [cited 2017 Mar 7];144(6):1252–61. Available from: . Layer P, Yamamoto H, Kalthoff L, Clain JE, Bakken LJ, DiMagno EP. The different courses of early- and late-onset idiopathic and alcoholic chronic pancreatitis. 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