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Name of journal: World Journal of GastroenterologyManuscript NO: 49569Manuscript type: MinireviewsRole of endoscopic ultrasound in the screening and follow-up of high-risk individuals for familial pancreatic cancerLorenzo D et al. Endoscopic ultrasound in familial pancreatic cancerDiane Lorenzo, Vinciane Rebours, Frédérique Maire, Maxime Palazzo, Jean-Michel Gonzalez, Marie-Pierre Vullierme, Alain Aubert, Pascal Hammel, Philippe Lévy, Louis de MestierDiane Lorenzo, Vinciane Rebours, Frédérique Maire, Maxime Palazzo, Alain Aubert, Philippe Lévy, Louis de Mestier, Pancreatology Department, Beaujon Hospital, Assistance Publique-H?pitaux de Paris, Clichy, and Paris Diderot University, Paris 75013, FranceVinciane Rebours, Louis de Mestier, INSERM, UMR1149, Paris 92110, FranceJean-Michel Gonzalez, Departement of Gastroenterology, Aix Marseille university - APHM - H?pital Nord, Marseille 13000, FranceMarie-Pierre Vullierme, Radiology Department, Beaujon Hospital, Assistance Publique-H?pitaux de Paris, Clichy, and Paris Diderot University, Paris 92110, FrancePascal Hammel, Oncology Department, Beaujon Hospital, Assistance Publique-H?pitaux de Paris, Clichy, and Paris Diderot University, Paris 92110, FranceORCID number: Diane Lorenzo (0000-0002-3729-8416); Vinciane Rebours (0000-0002-0000-4525); Frédérique Maire (0000-0001-9703-7018); Maxime Palazzo ( HYPERLINK "" \t "_blank" 0000-0003-3500-2914); Jean-Michel Gonzalez ( HYPERLINK "" \t "_blank" 0000-0001-5772-8236); Marie-Pierre Vullierme ( HYPERLINK "" \t "_blank" 0000-0002-3667-8943); Alain Aubert (0000-0001-9400-6152); Pascal Hammel ( HYPERLINK "" \t "_blank" 0000-0002-4630-4996); Philippe Lévy ( HYPERLINK "" \t "_blank" 0000-0002-0750-3351); Louis de Mestier ( HYPERLINK "" \t "_blank" 0000-0001-9715-9189).Author contributions: Lorenzo D, Rebours V, Lévy P and de Mestier L designed research; Lorenzo D, Rebours V, Maire F, Palazzo M, Gonzalez JM, Vullierme MP, Aubert A, Hammel P, Lévy P and de Mestier L performed research; Lorenzo D, Rebours V, Lévy P and de Mestier L contributed analytic tools; Lorenzo D, Rebours V, Maire F, Palazzo M, Gonzalez JM, Vullierme MP, Aubert A, Hammel P, Lévy P and de Mestier L analyzed data; Lorenzo D, Rebours V, Maire F, Palazzo M, Gonzalez JM, Vullierme MP, Aubert A, Hammel P, Lévy P and de Mestier L wrote the paper. Conflict-of-interest statement: All the authors declare no potential conflict of interest in relation with this work.Open-Access: This is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: : Invited ManuscriptCorresponding author: Diane Lorenzo, MD, Doctor, P?le des Maladies de l’Appareil Digestif, Service de Pancréatologie-Gastroentérologie, H?pital BEAUJON, 100 boulevard du Général Leclerc, Clichy, Paris 75013, France. diane.lorenzo@aphp.frTelephone: 33-1-40875215Fax: 33-1-42703784Received: June 5, 2019Peer-review started: June 5, 2019First decision: July 21, 2019Revised: August 4, 2019Accepted: August 24, 2019 Article in press: August 24, 2019Published online: September 14, 2019AbstractManaging familial pancreatic cancer (FPC) is challenging for gastroenterologists, surgeons and oncologists. High-risk individuals (HRI) for pancreatic cancer (PC) (FPC or with germline mutations) are a heterogeneous group of subjects with a theoretical lifetime cumulative risk of PC over 5%. Screening is mainly based on annual magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS). The goal of screening is to identify early-stage operable cancers or high-risk precancerous lesions (pancreatic intraepithelial neoplasia or intraductal papillary mucinous neoplasms with high-grade dysplasia). In the literature, target lesions are identified in 2%-5% of HRI who undergo screening. EUS appears to provide better identification of small solid lesions (0%-46% of HRI) and chronic-pancreatitis-like parenchymal changes (14%-77% of HRI), while MRI is probably the best modality to identify small cystic lesions (13%-49% of HRI). There are no specific studies in HRI on the use of contrast-enhanced harmonic EUS. EUS can also be used to obtain tissue samples. Nevertheless, there is still limited evidence on the accuracy of imaging procedures used for screening or agreement on which patients to treat. The cost-effectiveness of screening is also unclear. Certain new EUS-related techniques, such as searching for DNA abnormalities or protein markers in pancreatic fluid, appear to be promising.Key words: Endoscopic ultrasound; Familial pancreatic cancer; Fine-needle aspiration; Intraductal papillary mucinous neoplasm; Pancreatic cancer; Pancreatic intraepithelial neoplasia; Pancreatic cancer screening guidelines? The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved. Core tip: High-risk individuals (HRI) for pancreatic cancer have a lifetime cumulative risk of this disorder of over 5%. The goal of screening is to identify operable cancers or precancerous lesions. Endoscopic ultrasound (EUS) appears to better identify solid lesions (0%-46% of HRI) and chronic-pancreatitis-like parenchymal changes (14%-77%), and magnetic resonance imaging to better identify small cysts (13%-49%). EUS is used to obtain tissue samples. There are no specific studies on contrast-enhanced harmonic-EUS in HRI. There is limited evidence on the accuracy of imaging used for screening or agreement on which patients to treat. The cost-effectiveness of screening is also unclear. New EUS-related techniques (identifying DNA abnormalities or protein markers) appear to be promising.Lorenzo D, Rebours V, Maire F, Palazzo M, Gonzalez JM, Vullierme MP, Aubert A, Hammel P, Lévy P, de Mestier L. Role of endoscopic ultrasound in the screening and follow-up of high-risk individuals for familial pancreatic cancer. World J Gastroenterol 2019; 25(34): 5082-5096URL: : the past few decades, the incidence of pancreatic cancer (PC) has continuously increased, while its prognosis remains poor, with a 5-year survival rate < 10% for all stages analysed together. PC is expected to become the second leading cause of cancer-related death in the United States in 2030 ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"V1l0FV9A","properties":{"formattedCitation":"\\super [1]\\nosupersub{}","plainCitation":"[1]","noteIndex":0},"citationItems":[{"id":"BbVydael/n3Iv3BxX","uris":[""],"uri":[""],"itemData":{"id":145,"type":"article-journal","title":"Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States","container-title":"Cancer Research","page":"2913-2921","volume":"74","issue":"11","source":"PubMed","abstract":"Cancer incidence and deaths in the United States were projected for the most common cancer types for the years 2020 and 2030 based on changing demographics and the average annual percentage changes in incidence and death rates. Breast, prostate, and lung cancers will remain the top cancer diagnoses throughout this time, but thyroid cancer will replace colorectal cancer as the fourth leading cancer diagnosis by 2030, and melanoma and uterine cancer will become the fifth and sixth most common cancers, respectively. Lung cancer is projected to remain the top cancer killer throughout this time period. However, pancreas and liver cancers are projected to surpass breast, prostate, and colorectal cancers to become the second and third leading causes of cancer-related death by 2030, respectively. Advances in screening, prevention, and treatment can change cancer incidence and/or death rates, but it will require a concerted effort by the research and healthcare communities now to effect a substantial change for the future.","DOI":"10.1158/0008-5472.CAN-14-0155","ISSN":"1538-7445","note":"PMID: 24840647","title-short":"Projecting cancer incidence and deaths to 2030","journalAbbreviation":"Cancer Res.","language":"eng","author":[{"family":"Rahib","given":"Lola"},{"family":"Smith","given":"Benjamin D."},{"family":"Aizenberg","given":"Rhonda"},{"family":"Rosenzweig","given":"Allison B."},{"family":"Fleshman","given":"Julie M."},{"family":"Matrisian","given":"Lynn M."}],"issued":{"date-parts":[["2014",6,1]]}}}],"schema":""} [1]. Early-stage surgical resection is the only potentially curative treatment that increases survival. However, complete surgical resection can only be performed in a minority of patients, since 80% of patients have metastatic or locoregionally advanced disease at diagnosis ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"muVSFlnY","properties":{"formattedCitation":"\\super [1\\uc0\\u8211{}3]\\nosupersub{}","plainCitation":"[1–3]","noteIndex":0},"citationItems":[{"id":"BbVydael/bt2cFKVE","uris":[""],"uri":[""],"itemData":{"id":143,"type":"article-journal","title":"State of the art and future directions of pancreatic ductal adenocarcinoma therapy","container-title":"Pharmacology & Therapeutics","page":"80-104","volume":"155","source":"PubMed","abstract":"Pancreatic ductal adenocarcinoma (PDAC) is expected to become the second cause of cancer-related death in 2030. PDAC is the poorest prognostic tumor of the digestive tract, with 80% of patients having advanced disease at diagnosis and 5-year survival rate not exceeding 7%. Until 2010, gemcitabine was the only validated therapy for advanced PDAC with a modest improvement in median overall survival as compared to best supportive care (5-6 vs 3 months). Multiple phase II-III studies have used various combinations of gemcitabine with other cytotoxics or targeted agents, most in vain, in attempt to improve this outcome. Over the past few years, the landscape of PDAC management has undergone major and rapid changes with the approval of the FOLFIRINOX and gemcitabine plus nab-paclitaxel regimens in patients with metastatic disease. These two active combination chemotherapy options yield an improved median overall survival (11.1 vs 8.5 months, respectively) thus making longer survival a reasonably achievable goal. This breakthrough raises some new clinical questions about the management of PDAC. Moreover, better knowledge of the environmental and genetic events that underpin multistep carcinogenesis and of the microenvironment surrounding cancer cells in PDAC has open new perspectives and therapeutic opportunities. In this new dynamic context of deep transformation in basic research and clinical management aspects of the disease, we gathered updated preclinical and clinical data in a multifaceted review encompassing the lessons learned from the past, the yet unanswered questions, and the most promising research priorities to be addressed for the next 5 years.","DOI":"10.1016/j.pharmthera.2015.08.006","ISSN":"1879-016X","note":"PMID: 26299994","journalAbbreviation":"Pharmacol. Ther.","language":"eng","author":[{"family":"Neuzillet","given":"Cindy"},{"family":"Tijeras-Raballand","given":"Annemila?"},{"family":"Bourget","given":"Philippe"},{"family":"Cros","given":"Jér?me"},{"family":"Couvelard","given":"Anne"},{"family":"Sauvanet","given":"Alain"},{"family":"Vullierme","given":"Marie-Pierre"},{"family":"Tournigand","given":"Christophe"},{"family":"Hammel","given":"Pascal"}],"issued":{"date-parts":[["2015",11]]}}},{"id":"BbVydael/n3Iv3BxX","uris":[""],"uri":[""],"itemData":{"id":145,"type":"article-journal","title":"Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States","container-title":"Cancer Research","page":"2913-2921","volume":"74","issue":"11","source":"PubMed","abstract":"Cancer incidence and deaths in the United States were projected for the most common cancer types for the years 2020 and 2030 based on changing demographics and the average annual percentage changes in incidence and death rates. Breast, prostate, and lung cancers will remain the top cancer diagnoses throughout this time, but thyroid cancer will replace colorectal cancer as the fourth leading cancer diagnosis by 2030, and melanoma and uterine cancer will become the fifth and sixth most common cancers, respectively. Lung cancer is projected to remain the top cancer killer throughout this time period. However, pancreas and liver cancers are projected to surpass breast, prostate, and colorectal cancers to become the second and third leading causes of cancer-related death by 2030, respectively. Advances in screening, prevention, and treatment can change cancer incidence and/or death rates, but it will require a concerted effort by the research and healthcare communities now to effect a substantial change for the future.","DOI":"10.1158/0008-5472.CAN-14-0155","ISSN":"1538-7445","note":"PMID: 24840647","title-short":"Projecting cancer incidence and deaths to 2030","journalAbbreviation":"Cancer Res.","language":"eng","author":[{"family":"Rahib","given":"Lola"},{"family":"Smith","given":"Benjamin D."},{"family":"Aizenberg","given":"Rhonda"},{"family":"Rosenzweig","given":"Allison B."},{"family":"Fleshman","given":"Julie M."},{"family":"Matrisian","given":"Lynn M."}],"issued":{"date-parts":[["2014",6,1]]}}},{"id":"BbVydael/4Nxojman","uris":[""],"uri":[""],"itemData":{"id":138,"type":"article-journal","title":"Is early diagnosis of pancreatic cancer fiction? Surveillance of individuals at high risk for pancreatic cancer","container-title":"Digestive Diseases (Basel, Switzerland)","page":"670-678","volume":"28","issue":"4-5","source":"PubMed","abstract":"Pancreatic cancer represents one of the most deadly human malignancies with an overall 5-year survival of less than 5%. Despite improvements in imaging techniques and surgical techniques, survival statistics have hardly improved over the past decades. To improve the dismal outlook it would be highly desirable to develop a program to detect precursor lesions or small asymptomatic early cancers at the time when the disease is still at a curable stage. Screening the general population for disease presence is not feasible at present because of the relatively low disease incidence and the lack of a noninvasive, reliable and cheap screening tool. Targeted surveillance programs, however, in individuals at high risk for developing pancreatic cancer, like mutation carriers of pancreatic cancer prone hereditary (tumor) syndromes or individuals with a strong family history of pancreatic cancer without a known underlying genetic defect, might be feasible. Careful consideration of the criteria put forward by Wilson and Jungner as published by the World Health Organization on the principles and practice of screening for disease, indicate that surveillance in this high-risk population by means of endosonography (EUS) and/or magnetic resonance imaging (MRI) represents a promising development, though experimental. It nicely points out which open questions need to be addressed. Among others, these include how to acquire a better understanding of the natural behavior and progression of precursor lesions towards invasive cancer, how to firmly establish the performance characteristics of EUS and MRI for the detection of (early) lesions in individuals at high risk for pancreatic cancer, and how to determine which lesions can be safely observed with continued surveillance and which lesions justify resection.","DOI":"10.1159/000320095","ISSN":"1421-9875","note":"PMID: 21088419","title-short":"Is early diagnosis of pancreatic cancer fiction?","journalAbbreviation":"Dig Dis","language":"eng","author":[{"family":"Harinck","given":"F."},{"family":"Poley","given":"J. W."},{"family":"Kluijt","given":"I."},{"family":"Fockens","given":"P."},{"family":"Bruno","given":"M. J."},{"literal":"Dutch Research Group of Pancreatic Cancer Surveillance in High-Risk Individuals"}],"issued":{"date-parts":[["2010"]]}}}],"schema":""} [1–3]. Five to 10% of PCs are considered to be inherited ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"TmiKUhlh","properties":{"formattedCitation":"\\super [4,5]\\nosupersub{}","plainCitation":"[4,5]","noteIndex":0},"citationItems":[{"id":"BbVydael/zZTZnNXC","uris":[""],"uri":[""],"itemData":{"id":36,"type":"article-journal","title":"Refinement of screening for familial pancreatic cancer","container-title":"Gut","page":"1314-1321","volume":"65","issue":"8","source":"PubMed","abstract":"OBJECTIVE: Surveillance programmes are recommended for individuals at risk (IAR) of familial pancreatic cancer (FPC) to detect early pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC). However, the age to begin screening and the optimal screening protocol remain to be determined.\nMETHODS: IAR from non-CDKN2A FPC families underwent annual screening by MRI with endoscopic ultrasonography (EUS) in board-approved prospective screening programmes at three tertiary referral centres. The diagnostic yield according to age and different screening protocols was analysed.\nRESULTS: 253 IAR with a median age of 48 (25-81)?years underwent screening with a median of 3 (1-11) screening visits during a median follow-up of 28 (1-152)?months. 134 (53%) IAR revealed pancreatic lesions on imaging, mostly cystic (94%), on baseline or follow-up screening. Lesions were significantly more often identified in IAR above the age of 45?years (p<0.0001). In 21 IAR who underwent surgery, no significant lesions (PDAC, pancreatic intraepithelial neoplasia (PanIN) 3 lesions, high-grade intraductal papillary mucinous neoplasia (IPMN)) were detected before the age of 50?years. Potentially relevant lesions (multifocal PanIN2 lesions, low/moderate-grade branch-duct IPMNs) occurred also significantly more often after the age of 50?years (13 vs 2, p<0.0004). The diagnostic yield of potentially relevant lesions was not different between screening protocols using annual MRI with EUS (n=98) or annual MRI with EUS every 3rd year (n=198) and between IAR screened at intervals of 12?months (n=180) or IAR that decided to be screened at ≥24?months intervals (n=30).\nCONCLUSIONS: It appears safe to start screening for PDAC in IAR of non-CDKN2a FPC families at the age of 50?years. MRI-based screening supplemented by EUS at baseline and every 3rd year or when changes in MRI occur appears to be efficient.","DOI":"10.1136/gutjnl-2015-311098","ISSN":"1468-3288","note":"PMID: 27222532","journalAbbreviation":"Gut","language":"eng","author":[{"family":"Bartsch","given":"D. K."},{"family":"Slater","given":"E. P."},{"family":"Carrato","given":"A."},{"family":"Ibrahim","given":"I. S."},{"family":"Guillen-Ponce","given":"C."},{"family":"Vasen","given":"H. F. A."},{"family":"Matth?i","given":"E."},{"family":"Earl","given":"J."},{"family":"Jendryschek","given":"F. S."},{"family":"Figiel","given":"J."},{"family":"Steinkamp","given":"M."},{"family":"Ramaswamy","given":"A."},{"family":"Vázquez-Sequeiros","given":"E."},{"family":"Mu?oz-Beltran","given":"M."},{"family":"Montans","given":"J."},{"family":"Mocci","given":"E."},{"family":"Bonsing","given":"B. A."},{"family":"Wasser","given":"M."},{"family":"Kl?ppel","given":"G."},{"family":"Langer","given":"P."},{"family":"Fendrich","given":"V."},{"family":"Gress","given":"T. M."}],"issued":{"date-parts":[["2016"]]}}},{"id":"BbVydael/UNOH7UGY","uris":[""],"uri":[""],"itemData":{"id":29,"type":"article-journal","title":"Screening in GI Cancers: The Role of Genetics","container-title":"Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology","page":"1721-1728","volume":"33","issue":"16","source":"PubMed","abstract":"Genetic and epigenetic alterations identified in tumors of different cancer types can provide insights regarding the roles played by different cell signaling pathways in carcinogenesis. Somatic mutation profiles of GI tumors are used to guide choice of chemotherapy and can facilitate identification of individuals whose cancers arise in the setting of genetic predisposition. This review provides a framework for how clinical history, family history of cancer, and tumor genomic phenotype can be used to screen patients with colorectal, gastric, or pancreatic cancer for hereditary cancer syndromes. Early identification of individuals who carry germline mutations can affect clinical care not only for patients with cancer but also for their at-risk relatives.","DOI":"10.1200/JCO.2014.60.6764","ISSN":"1527-7755","note":"PMID: 25918283","title-short":"Screening in GI Cancers","journalAbbreviation":"J. Clin. Oncol.","language":"eng","author":[{"family":"Stoffel","given":"Elena M."}],"issued":{"date-parts":[["2015",6,1]]}}}],"schema":""} [4,5]. While pathogenic germline mutations in specific genes have been associated with an increased risk of PC (from 4% to 40%), a causal germline mutation is identified in fewer than 20% of these families ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1ImVV0Iw","properties":{"formattedCitation":"\\super [6\\uc0\\u8211{}10]\\nosupersub{}","plainCitation":"[6–10]","noteIndex":0},"citationItems":[{"id":"BbVydael/ATi5U74k","uris":[""],"uri":[""],"itemData":{"id":19,"type":"article-journal","title":"International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer","container-title":"Gut","page":"339-347","volume":"62","issue":"3","source":"PubMed","abstract":"BACKGROUND: Screening individuals at increased risk for pancreatic cancer (PC) detects early, potentially curable, pancreatic neoplasia.\nOBJECTIVE: To develop consortium statements on screening, surveillance and management of high-risk individuals with an inherited predisposition to PC.\nMETHODS: A 49-expert multidisciplinary international consortium met to discuss pancreatic screening and vote on statements. Consensus was considered reached if ≥ 75% agreed or disagreed.\nRESULTS: There was excellent agreement that, to be successful, a screening programme should detect and treat T1N0M0 margin-negative PC and high-grade dysplastic precursor lesions (pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasm). It was agreed that the following were candidates for screening: first-degree relatives (FDRs) of patients with PC from a familial PC kindred with at least two affected FDRs; patients with Peutz-Jeghers syndrome; and p16, BRCA2 and hereditary non-polyposis colorectal cancer (HNPCC) mutation carriers with ≥ 1 affected FDR. Consensus was not reached for the age to initiate screening or stop surveillance. It was agreed that initial screening should include endoscopic ultrasonography (EUS) and/or MRI/magnetic resonance cholangiopancreatography not CT or endoscopic retrograde cholangiopancreatography. There was no consensus on the need for EUS fine-needle aspiration to evaluate cysts. There was disagreement on optimal screening modalities and intervals for follow-up imaging. When surgery is recommended it should be performed at a high-volume centre. There was great disagreement as to which screening abnormalities were of sufficient concern to for surgery to be recommended.\nCONCLUSIONS: Screening is recommended for high-risk individuals, but more evidence is needed, particularly for how to manage patients with detected lesions. Screening and subsequent management should take place at high-volume centres with multidisciplinary teams, preferably within research protocols.","DOI":"10.1136/gutjnl-2012-303108","ISSN":"1468-3288","note":"PMID: 23135763\nPMCID: PMC3585492","journalAbbreviation":"Gut","language":"eng","author":[{"family":"Canto","given":"Marcia Irene"},{"family":"Harinck","given":"Femme"},{"family":"Hruban","given":"Ralph H."},{"family":"Offerhaus","given":"George Johan"},{"family":"Poley","given":"Jan-Werner"},{"family":"Kamel","given":"Ihab"},{"family":"Nio","given":"Yung"},{"family":"Schulick","given":"Richard S."},{"family":"Bassi","given":"Claudio"},{"family":"Kluijt","given":"Irma"},{"family":"Levy","given":"Michael J."},{"family":"Chak","given":"Amitabh"},{"family":"Fockens","given":"Paul"},{"family":"Goggins","given":"Michael"},{"family":"Bruno","given":"Marco"},{"literal":"International Cancer of Pancreas Screening (CAPS) Consortium"}],"issued":{"date-parts":[["2013",3]]}}},{"id":"BbVydael/WgkkkMl5","uris":[""],"uri":[""],"itemData":{"id":22,"type":"article-journal","title":"Risk of pancreatic cancer in families with Lynch syndrome","container-title":"JAMA","page":"1790-1795","volume":"302","issue":"16","source":"PubMed","abstract":"CONTEXT: Lynch syndrome is an inherited cause of colorectal cancer caused by mutations of DNA mismatch repair (MMR) genes. A number of extracolonic tumors have been associated with the disorder, including pancreatic cancer; however, the risk of pancreatic cancer in Lynch syndrome is uncertain and not quantified.\nOBJECTIVE: To estimate pancreatic cancer risk in families with germline MMR gene mutations.\nDESIGN, SETTING, AND PATIENTS: Cancer histories of probands and their relatives were evaluated in MMR gene mutation carriers in the familial cancer registries of the Dana-Farber Cancer Institute (n = 80), Boston, Massachusetts, and University of Michigan Comprehensive Cancer Center (n = 67), Ann Arbor, Michigan. Families enrolled before the study start date (June 2008) were eligible. Age-specific cumulative risks and hazard ratio estimates of pancreatic cancer risk were calculated and compared with the general population using modified segregation analysis, with correction for ascertainment.\nMAIN OUTCOME MEASURES: Age-specific cumulative risks and hazard ratio estimates of pancreatic cancer risk.\nRESULTS: Data on 6342 individuals from 147 families with MMR gene mutations were analyzed. Thirty-one families (21.1%) reported at least 1 case of pancreatic cancer. Forty-seven pancreatic cancers were reported (21 men and 26 women), with no sex-related difference in age of diagnosis (51.5 vs 56.5 years for men and women, respectively). The cumulative risk of pancreatic cancer in these families with gene mutations was 1.31% (95% confidence interval [CI], 0.31%-2.32%) up to age 50 years and 3.68% (95% CI, 1.45%-5.88%) up to age 70 years, which represents an 8.6-fold increase (95% CI, 4.7-15.7) compared with the general population.\nCONCLUSIONS: Among 147 families with germline MMR gene mutations, the risk of pancreatic cancer was increased compared with the US population. Individuals with MMR gene mutations and a family history of pancreatic cancer are appropriate to include in studies to further define the risk of premalignant and malignant pancreatic neoplasms and potential benefits and limitations of surveillance.","DOI":"10.1001/jama.2009.1529","ISSN":"1538-3598","note":"PMID: 19861671\nPMCID: PMC4091624","journalAbbreviation":"JAMA","language":"eng","author":[{"family":"Kastrinos","given":"Fay"},{"family":"Mukherjee","given":"Bhramar"},{"family":"Tayob","given":"Nabihah"},{"family":"Wang","given":"Fei"},{"family":"Sparr","given":"Jennifer"},{"family":"Raymond","given":"Victoria M."},{"family":"Bandipalliam","given":"Prathap"},{"family":"Stoffel","given":"Elena M."},{"family":"Gruber","given":"Stephen B."},{"family":"Syngal","given":"Sapna"}],"issued":{"date-parts":[["2009",10,28]]}}},{"id":"BbVydael/OXSZDEa1","uris":[""],"uri":[""],"itemData":{"id":25,"type":"article-journal","title":"Very high risk of cancer in familial Peutz-Jeghers syndrome","container-title":"Gastroenterology","page":"1447-1453","volume":"119","issue":"6","source":"PubMed","abstract":"BACKGROUND & AIMS: The Peutz-Jeghers syndrome (PJS) is an autosomal dominant polyposis disorder with increased risk of multiple cancers, but literature estimates of risk vary.\nMETHODS: We performed an individual patient meta-analysis to determine the relative risk (RR) of cancer in patients with PJS compared with the general population based on 210 individuals described in 6 publications.\nRESULTS: For patients with PJS, the RR for all cancers was 15.2 (95% confidence limits [CL], 2, 19). A statistically significant increase of RR was noted for esophagus (57; CL, 2.5, 557), stomach (213; CL, 96, 368), small intestine (520; CL, 220, 1306), colon (84; CL, 47, 137), pancreas (132; CL, 44, 261), lung (17.0; CL, 5.4, 39), breast (15.2; CL, 7.6, 27), uterus (16.0; CL, 1.9, 56), ovary (27; CL, 7.3, 68), but not testicular or cervical malignancies. Cumulative risk for all cancer was 93% from age 15 to 64 years old.\nCONCLUSIONS: Patients with PJS are at very high relative and absolute risk for gastrointestinal and nongastrointestinal cancers.","ISSN":"0016-5085","note":"PMID: 11113065","journalAbbreviation":"Gastroenterology","language":"eng","author":[{"family":"Giardiello","given":"F. M."},{"family":"Brensinger","given":"J. D."},{"family":"Tersmette","given":"A. C."},{"family":"Goodman","given":"S. N."},{"family":"Petersen","given":"G. M."},{"family":"Booker","given":"S. V."},{"family":"Cruz-Correa","given":"M."},{"family":"Offerhaus","given":"J. A."}],"issued":{"date-parts":[["2000",12]]}}},{"id":"BbVydael/ZYFw4Opl","uris":[""],"uri":[""],"itemData":{"id":27,"type":"article-journal","title":"Association Between Inherited Germline Mutations in Cancer Predisposition Genes and Risk of Pancreatic Cancer","container-title":"JAMA","page":"2401-2409","volume":"319","issue":"23","source":"PubMed","abstract":"Importance: Individuals genetically predisposed to pancreatic cancer may benefit from early detection. Genes that predispose to pancreatic cancer and the risks of pancreatic cancer associated with mutations in these genes are not well defined.\nObjective: To determine whether inherited germline mutations in cancer predisposition genes are associated with increased risks of pancreatic cancer.\nDesign, Setting, and Participants: Case-control analysis to identify pancreatic cancer predisposition genes; longitudinal analysis of patients with pancreatic cancer for prognosis. The study included 3030 adults diagnosed as having pancreatic cancer and enrolled in a Mayo Clinic registry between October 12, 2000, and March 31, 2016, with last follow-up on June 22, 2017. Reference controls were 123?136 individuals with exome sequence data in the public Genome Aggregation Database and 53?105 in the Exome Aggregation Consortium database.\nExposures: Individuals were classified based on carrying a deleterious mutation in cancer predisposition genes and having a personal or family history of cancer.\nMain Outcomes and Measures: Germline mutations in coding regions of 21 cancer predisposition genes were identified by sequencing of products from a custom multiplex polymerase chain reaction-based panel; associations of genes with pancreatic cancer were assessed by comparing frequency of mutations in genes of pancreatic cancer patients with those of reference controls.\nResults: Comparing 3030 case patients with pancreatic cancer (43.2% female; 95.6% non-Hispanic white; mean age at diagnosis, 65.3 [SD, 10.7] years) with reference controls, significant associations were observed between pancreatic cancer and mutations in CDKN2A (0.3% of cases and 0.02% of controls; odds ratio [OR], 12.33; 95% CI, 5.43-25.61); TP53 (0.2% of cases and 0.02% of controls; OR, 6.70; 95% CI, 2.52-14.95); MLH1 (0.13% of cases and 0.02% of controls; OR, 6.66; 95% CI, 1.94-17.53); BRCA2 (1.9% of cases and 0.3% of controls; OR, 6.20; 95% CI, 4.62-8.17); ATM (2.3% of cases and 0.37% of controls; OR, 5.71; 95% CI, 4.38-7.33); and BRCA1 (0.6% of cases and 0.2% of controls; OR, 2.58; 95% CI, 1.54-4.05).\nConclusions and Relevance: In this case-control study, mutations in 6 genes associated with pancreatic cancer were found in 5.5% of all pancreatic cancer patients, including 7.9% of patients with a family history of pancreatic cancer and 5.2% of patients without a family history of pancreatic cancer. Further research is needed for replication in other populations.","DOI":"10.1001/jama.2018.6228","ISSN":"1538-3598","note":"PMID: 29922827\nPMCID: PMC6092184","journalAbbreviation":"JAMA","language":"eng","author":[{"family":"Hu","given":"Chunling"},{"family":"Hart","given":"Steven N."},{"family":"Polley","given":"Eric C."},{"family":"Gnanaolivu","given":"Rohan"},{"family":"Shimelis","given":"Hermela"},{"family":"Lee","given":"Kun Y."},{"family":"Lilyquist","given":"Jenna"},{"family":"Na","given":"Jie"},{"family":"Moore","given":"Raymond"},{"family":"Antwi","given":"Samuel O."},{"family":"Bamlet","given":"William R."},{"family":"Chaffee","given":"Kari G."},{"family":"DiCarlo","given":"John"},{"family":"Wu","given":"Zhong"},{"family":"Samara","given":"Raed"},{"family":"Kasi","given":"Pashtoon M."},{"family":"McWilliams","given":"Robert R."},{"family":"Petersen","given":"Gloria M."},{"family":"Couch","given":"Fergus J."}],"issued":{"date-parts":[["2018"]],"season":"19"}}},{"id":"BbVydael/jiIYxhxp","uris":[""],"uri":[""],"itemData":{"id":65,"type":"article-journal","title":"PanGen-Fam: Spanish registry of hereditary pancreatic cancer","container-title":"European Journal of Cancer (Oxford, England: 1990)","page":"1911-1917","volume":"51","issue":"14","source":"PubMed","abstract":"PURPOSE: To describe the organisation of the registry and the preliminary results in terms of characteristics of high-risk pancreatic ductal adenocarcinoma (PDAC) families recruited to date and findings of the screening programme. To compare early onset sporadic cases (?50 years), sporadic cases (>50 years) and cases with family history of cancer, for PDAC possible risk factors.\nMETHODS/PATIENTS: Families with hereditary cancer syndromes predisposing to PDAC were recruited from two main sources: Spanish hospitals participating in PanGenEU, a pan-European multicentre case-control study, and their genetic counseling unit. Individuals at high-risk of PDAC were enrolled into a screening programme, consisting of Endoscopic ultrasound, computerised tomography, magnetic resonance imaging. Genetic testing of candidate genes was offered according to each patient's risk.\nRESULTS: Among 577 consecutive PDAC cases, recruited via PanGenEU, 36 (6%) had ?2 first-degree relative with PDAC: Familial pancreatic cancer (FPC). So far PanGen-Fam has recruited 42 high-risk PDAC families; 25 (60%) had FPC. Five index cases with cancer were positive for BRCA2 and one for BRCA1 germline mutations. In the second year of prospective PDAC screening, one neuroendocrine tumour and a high-grade dysplasia lesion suspicious of carcinoma were diagnosed among 41 high-risk individuals. Furthermore EUS detected chronic-pancreatitis-like parenchymal changes in 15 patients.\nCONCLUDING STATEMENT: The identification and recruitment of PDAC high-risk families into the PanGen-Fam registry provides an opportunity to detect early onset cancer and precursor pancreatic cancer lesions at a potentially curative stage and to increase the knowledge of the natural history of the disease.","DOI":"10.1016/j.ejca.2015.07.004","ISSN":"1879-0852","note":"PMID: 26212471","title-short":"PanGen-Fam","journalAbbreviation":"Eur. J. Cancer","language":"eng","author":[{"family":"Mocci","given":"E."},{"family":"Guillen-Ponce","given":"C."},{"family":"Earl","given":"J."},{"family":"Marquez","given":"M."},{"family":"Solera","given":"J."},{"family":"Salazar-López","given":"M.-T."},{"family":"Calcedo-Arnáiz","given":"C."},{"family":"Vázquez-Sequeiros","given":"E."},{"family":"Montans","given":"J."},{"family":"Mu?oz-Beltrán","given":"M."},{"family":"Vicente-Bártulos","given":"A."},{"family":"González-Gordaliza","given":"C."},{"family":"Sanjuanbenito","given":"A."},{"family":"Guerrero","given":"C."},{"family":"Mendía","given":"E."},{"family":"Lisa","given":"E."},{"family":"Lobo","given":"E."},{"family":"Martínez","given":"J. C."},{"family":"Real","given":"F. X."},{"family":"Malats","given":"N."},{"family":"Carrato","given":"A."}],"issued":{"date-parts":[["2015",9]]}}}],"schema":""} [6–10]. Several gene abnormalities and related hereditary syndromes have been associated with an increased risk of PC: BRCA1 and BRCA2 (hereditary breast ovarian cancer syndrome), PALB2 and the genes involved in the Fanconi pathway, CDKN2A (familial atypical multiple mole melanoma: FAMMM), the genes involved in Lynch syndrome (mainly MLH1, MSH2, MSH6, and PMS2), PRSS1 (hereditary pancreatitis), STK11 (Peutz-Jeghers syndrome), TP53 (Li-Fraumeni syndrome), APC (familial adenomatous polyposis), and ATM (ataxia telangiectasia) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"kDBCfD0U","properties":{"formattedCitation":"\\super [4,9,11\\uc0\\u8211{}16]\\nosupersub{}","plainCitation":"[4,9,11–16]","noteIndex":0},"citationItems":[{"id":"BbVydael/zZTZnNXC","uris":[""],"uri":[""],"itemData":{"id":36,"type":"article-journal","title":"Refinement of screening for familial pancreatic cancer","container-title":"Gut","page":"1314-1321","volume":"65","issue":"8","source":"PubMed","abstract":"OBJECTIVE: Surveillance programmes are recommended for individuals at risk (IAR) of familial pancreatic cancer (FPC) to detect early pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC). However, the age to begin screening and the optimal screening protocol remain to be determined.\nMETHODS: IAR from non-CDKN2A FPC families underwent annual screening by MRI with endoscopic ultrasonography (EUS) in board-approved prospective screening programmes at three tertiary referral centres. The diagnostic yield according to age and different screening protocols was analysed.\nRESULTS: 253 IAR with a median age of 48 (25-81)?years underwent screening with a median of 3 (1-11) screening visits during a median follow-up of 28 (1-152)?months. 134 (53%) IAR revealed pancreatic lesions on imaging, mostly cystic (94%), on baseline or follow-up screening. Lesions were significantly more often identified in IAR above the age of 45?years (p<0.0001). In 21 IAR who underwent surgery, no significant lesions (PDAC, pancreatic intraepithelial neoplasia (PanIN) 3 lesions, high-grade intraductal papillary mucinous neoplasia (IPMN)) were detected before the age of 50?years. Potentially relevant lesions (multifocal PanIN2 lesions, low/moderate-grade branch-duct IPMNs) occurred also significantly more often after the age of 50?years (13 vs 2, p<0.0004). The diagnostic yield of potentially relevant lesions was not different between screening protocols using annual MRI with EUS (n=98) or annual MRI with EUS every 3rd year (n=198) and between IAR screened at intervals of 12?months (n=180) or IAR that decided to be screened at ≥24?months intervals (n=30).\nCONCLUSIONS: It appears safe to start screening for PDAC in IAR of non-CDKN2a FPC families at the age of 50?years. MRI-based screening supplemented by EUS at baseline and every 3rd year or when changes in MRI occur appears to be efficient.","DOI":"10.1136/gutjnl-2015-311098","ISSN":"1468-3288","note":"PMID: 27222532","journalAbbreviation":"Gut","language":"eng","author":[{"family":"Bartsch","given":"D. K."},{"family":"Slater","given":"E. P."},{"family":"Carrato","given":"A."},{"family":"Ibrahim","given":"I. S."},{"family":"Guillen-Ponce","given":"C."},{"family":"Vasen","given":"H. F. A."},{"family":"Matth?i","given":"E."},{"family":"Earl","given":"J."},{"family":"Jendryschek","given":"F. S."},{"family":"Figiel","given":"J."},{"family":"Steinkamp","given":"M."},{"family":"Ramaswamy","given":"A."},{"family":"Vázquez-Sequeiros","given":"E."},{"family":"Mu?oz-Beltran","given":"M."},{"family":"Montans","given":"J."},{"family":"Mocci","given":"E."},{"family":"Bonsing","given":"B. A."},{"family":"Wasser","given":"M."},{"family":"Kl?ppel","given":"G."},{"family":"Langer","given":"P."},{"family":"Fendrich","given":"V."},{"family":"Gress","given":"T. M."}],"issued":{"date-parts":[["2016"]]}}},{"id":"BbVydael/ZYFw4Opl","uris":[""],"uri":[""],"itemData":{"id":27,"type":"article-journal","title":"Association Between Inherited Germline Mutations in Cancer Predisposition Genes and Risk of Pancreatic Cancer","container-title":"JAMA","page":"2401-2409","volume":"319","issue":"23","source":"PubMed","abstract":"Importance: Individuals genetically predisposed to pancreatic cancer may benefit from early detection. Genes that predispose to pancreatic cancer and the risks of pancreatic cancer associated with mutations in these genes are not well defined.\nObjective: To determine whether inherited germline mutations in cancer predisposition genes are associated with increased risks of pancreatic cancer.\nDesign, Setting, and Participants: Case-control analysis to identify pancreatic cancer predisposition genes; longitudinal analysis of patients with pancreatic cancer for prognosis. The study included 3030 adults diagnosed as having pancreatic cancer and enrolled in a Mayo Clinic registry between October 12, 2000, and March 31, 2016, with last follow-up on June 22, 2017. Reference controls were 123?136 individuals with exome sequence data in the public Genome Aggregation Database and 53?105 in the Exome Aggregation Consortium database.\nExposures: Individuals were classified based on carrying a deleterious mutation in cancer predisposition genes and having a personal or family history of cancer.\nMain Outcomes and Measures: Germline mutations in coding regions of 21 cancer predisposition genes were identified by sequencing of products from a custom multiplex polymerase chain reaction-based panel; associations of genes with pancreatic cancer were assessed by comparing frequency of mutations in genes of pancreatic cancer patients with those of reference controls.\nResults: Comparing 3030 case patients with pancreatic cancer (43.2% female; 95.6% non-Hispanic white; mean age at diagnosis, 65.3 [SD, 10.7] years) with reference controls, significant associations were observed between pancreatic cancer and mutations in CDKN2A (0.3% of cases and 0.02% of controls; odds ratio [OR], 12.33; 95% CI, 5.43-25.61); TP53 (0.2% of cases and 0.02% of controls; OR, 6.70; 95% CI, 2.52-14.95); MLH1 (0.13% of cases and 0.02% of controls; OR, 6.66; 95% CI, 1.94-17.53); BRCA2 (1.9% of cases and 0.3% of controls; OR, 6.20; 95% CI, 4.62-8.17); ATM (2.3% of cases and 0.37% of controls; OR, 5.71; 95% CI, 4.38-7.33); and BRCA1 (0.6% of cases and 0.2% of controls; OR, 2.58; 95% CI, 1.54-4.05).\nConclusions and Relevance: In this case-control study, mutations in 6 genes associated with pancreatic cancer were found in 5.5% of all pancreatic cancer patients, including 7.9% of patients with a family history of pancreatic cancer and 5.2% of patients without a family history of pancreatic cancer. Further research is needed for replication in other populations.","DOI":"10.1001/jama.2018.6228","ISSN":"1538-3598","note":"PMID: 29922827\nPMCID: PMC6092184","journalAbbreviation":"JAMA","language":"eng","author":[{"family":"Hu","given":"Chunling"},{"family":"Hart","given":"Steven N."},{"family":"Polley","given":"Eric C."},{"family":"Gnanaolivu","given":"Rohan"},{"family":"Shimelis","given":"Hermela"},{"family":"Lee","given":"Kun Y."},{"family":"Lilyquist","given":"Jenna"},{"family":"Na","given":"Jie"},{"family":"Moore","given":"Raymond"},{"family":"Antwi","given":"Samuel O."},{"family":"Bamlet","given":"William R."},{"family":"Chaffee","given":"Kari G."},{"family":"DiCarlo","given":"John"},{"family":"Wu","given":"Zhong"},{"family":"Samara","given":"Raed"},{"family":"Kasi","given":"Pashtoon M."},{"family":"McWilliams","given":"Robert R."},{"family":"Petersen","given":"Gloria M."},{"family":"Couch","given":"Fergus J."}],"issued":{"date-parts":[["2018"]],"season":"19"}}},{"id":"BbVydael/iMJ7y1A2","uris":[""],"uri":[""],"itemData":{"id":33,"type":"article-journal","title":"Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma: a patient-level meta-analysis and proposition of the Beaujon score","container-title":"United European Gastroenterology Journal","page":"205064061882491","source":"Crossref","DOI":"10.1177/2050640618824910","ISSN":"2050-6406, 2050-6414","title-short":"Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma","language":"en","author":[{"family":"Mestier","given":"Louis","non-dropping-particle":"de"},{"family":"Muller","given":"Marie"},{"family":"Cros","given":"Jér?me"},{"family":"Vullierme","given":"Marie-Pierre"},{"family":"Vernerey","given":"Dewi"},{"family":"Maire","given":"Frédérique"},{"family":"Dokmak","given":"Safi"},{"family":"Rebours","given":"Vinciane"},{"family":"Sauvanet","given":"Alain"},{"family":"Lévy","given":"Philippe"},{"family":"Hammel","given":"Pascal"}],"issued":{"date-parts":[["2019",1,12]]}}},{"id":"BbVydael/Y8fwuXm1","uris":[""],"uri":[""],"itemData":{"id":44,"type":"article-journal","title":"Screening for pancreatic neoplasia in high-risk individuals: an EUS-based approach","container-title":"Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association","page":"606-621","volume":"2","issue":"7","source":"PubMed","abstract":"BACKGROUND & AIMS: Relatives of patients with pancreatic cancer and persons with certain inherited syndromes are at increased risk for developing pancreatic cancer. We prospectively evaluated the feasibility of screening for pancreatic neoplasia in high-risk individuals.\nMETHODS: Individuals from familial pancreatic cancer kindreds and a patient with Peutz-Jeghers syndrome underwent screening endoscopic ultrasound (EUS). If the EUS was abnormal, EUS-guided fine-needle aspiration, endoscopic retrograde cholangiopancreatography (ERCP), and spiral computed tomography (CT) were performed. Patients with abnormalities suggesting neoplasia had surgery.\nRESULTS: Thirty-eight patients were studied; 31 (mean age, 58 yr; 42% men) from kindreds with > or =3 affected with pancreatic cancer; 6 from kindreds with 2 affected relatives, 1 was a patient with Peutz-Jeghers syndrome. None had symptoms referable to the pancreas or suggestive of malignancy. Six pancreatic masses were found by EUS: 1 invasive ductal adenocarcinoma, 1 benign intraductal papillary mucinous neoplasm, 2 serous cystadenomas, and 2 nonneoplastic masses. Hence, the diagnostic yield for detecting clinically significant pancreatic neoplasms was 5.3% (2 of 38). The 1 patient with pancreatic cancer was treated and still is alive and disease-free >5 years after surgery. EUS changes similar to those associated with chronic pancreatitis were found, which were more common in patients with a history of regular alcohol intake (P = 0.02), but also occurred in patients who did not consume alcohol. Screening also led to a new diagnosis and treatment of symptomatic upper-gastrointestinal conditions in 18.4% of patients.\nCONCLUSIONS: EUS-based screening of asymptomatic high-risk individuals can detect prevalent resectable pancreatic neoplasia but false-positive diagnoses also occur.","ISSN":"1542-3565","note":"PMID: 15224285","title-short":"Screening for pancreatic neoplasia in high-risk individuals","journalAbbreviation":"Clin. Gastroenterol. Hepatol.","language":"eng","author":[{"family":"Canto","given":"Marcia Irene"},{"family":"Goggins","given":"Michael"},{"family":"Yeo","given":"Charles J."},{"family":"Griffin","given":"Constance"},{"family":"Axilbund","given":"Jennifer E."},{"family":"Brune","given":"Kieran"},{"family":"Ali","given":"Syed Z."},{"family":"Jagannath","given":"Sanjay"},{"family":"Petersen","given":"Gloria M."},{"family":"Fishman","given":"Elliot K."},{"family":"Piantadosi","given":"Steven"},{"family":"Giardiello","given":"Francis M."},{"family":"Hruban","given":"Ralph H."}],"issued":{"date-parts":[["2004",7]]}}},{"id":"BbVydael/1nFkaaQF","uris":[""],"uri":[""],"itemData":{"id":50,"type":"article-journal","title":"The yield of first-time endoscopic ultrasonography in screening individuals at a high risk of developing pancreatic cancer","container-title":"The American Journal of Gastroenterology","page":"2175-2181","volume":"104","issue":"9","source":"PubMed","abstract":"OBJECTIVES: Approximately 10-15% of all pancreatic cancers (PCs) may be hereditary in origin. We investigated the use of endoscopic ultrasonography (EUS) for the screening of individuals at high risk for developing PC. In this paper the results of first-time screening with EUS are presented.\nMETHODS: Those eligible for screening in this study were first-degree family members of affected individuals from familial pancreatic cancer (FPC) families, mutation carriers of PC-prone hereditary syndromes, individuals with Peutz-Jeghers syndrome, and mutation carriers of other PC-prone hereditary syndromes with clustering (> or =2 cases per family) of PC. All individuals were asymptomatic and had not undergone EUS before.\nRESULTS: Forty-four individuals (M/F 18/26), aged 32-75 years underwent screening with EUS. Thirteen were from families with familial atypical multiple-mole melanoma (FAMMM), 21 with FPC, 3 individuals were diagnosed with hereditary pancreatitis, 2 were Peutz-Jeghers patients, 3 were BRCA1 and 2 were BRCA2 mutation carriers with familial clustering of PC, and 1 individual had a p53 mutation. Three (6.8%) patients had an asymptomatic mass lesion (12, 27, and 50 mm) in the body (n=2) or tail of the pancreas. All lesions were completely resected. Pathology showed moderately differentiated adenocarcinomas with N1 disease in the two patients with the largest lesions. EUS showed branch-type intraductal papillary mucinous neoplasia (IPMN) in seven individuals.\nCONCLUSIONS: Screening of individuals at a high risk for PC with EUS is feasible and safe. The incidence of clinically relevant findings at first screening is high with asymptomatic cancer in 7% and premalignant IPMN-like lesions in 16% in our series. Whether screening improves survival remains to be determined, as does the optimal screening interval with EUS.","DOI":"10.1038/ajg.2009.276","ISSN":"1572-0241","note":"PMID: 19491823","journalAbbreviation":"Am. J. Gastroenterol.","language":"eng","author":[{"family":"Poley","given":"J. W."},{"family":"Kluijt","given":"I."},{"family":"Gouma","given":"D. J."},{"family":"Harinck","given":"F."},{"family":"Wagner","given":"A."},{"family":"Aalfs","given":"C."},{"family":"Eijck","given":"C. H. J.","non-dropping-particle":"van"},{"family":"Cats","given":"A."},{"family":"Kuipers","given":"E. J."},{"family":"Nio","given":"Y."},{"family":"Fockens","given":"P."},{"family":"Bruno","given":"M. J."}],"issued":{"date-parts":[["2009",9]]}}},{"id":"BbVydael/L7ID64fl","uris":[""],"uri":[""],"itemData":{"id":61,"type":"article-journal","title":"Promising outcomes of screening for pancreatic cancer by genetic testing and endoscopic ultrasound","container-title":"Pancreas","page":"458-461","volume":"43","issue":"3","source":"PubMed","abstract":"OBJECTIVE: This study aimed to determine if screening patients based on certain cancer syndromes or family history criteria can lead to early detection of pancreatic cancer.\nMETHODS: This was a cohort study from 2008 to 2011 at a large tertiary referral center. A total of 30 patients met high-risk criteria after genetic counseling and were referred to a gastroenterologist for possible endoscopic ultrasound (EUS).\nRESULTS: Of the 30 patients, 16 underwent EUS. Subsequently, 3 patients had fine needle aspiration. Two patients had pancreatic adenocarcinoma, and 1 patient had an intraductal papillary mucinous neoplasm with low-grade dysplasia. The 2 patients with pancreatic adenocarcinoma both had breast cancer and BRCA2 mutations. The patient with the intraductal papillary mucinous neoplasm had Peutz-Jeghers syndrome. All 3 patients underwent surgery and have remained cancer free.\nCONCLUSIONS: Genetic risk assessment with EUS +/- fine needle aspiration in high-risk patients may lead to earlier detection of pancreatic cancer and potentially improve overall morbidity and mortality. Greater emphasis should be placed on screening patients for hereditary cancer syndromes that increase the risk of pancreatic cancer.","DOI":"10.1097/MPA.0000000000000052","ISSN":"1536-4828","note":"PMID: 24622079","journalAbbreviation":"Pancreas","language":"eng","author":[{"family":"Sud","given":"Anchal"},{"family":"Wham","given":"Deborah"},{"family":"Catalano","given":"Marc"},{"family":"Guda","given":"Nalini M."}],"issued":{"date-parts":[["2014",4]]}}},{"id":"BbVydael/TT8LQAKI","uris":[""],"uri":[""],"itemData":{"id":79,"type":"article-journal","title":"Five years of prospective screening of high-risk individuals from families with familial pancreatic cancer","container-title":"Gut","page":"1410-1418","volume":"58","issue":"10","source":"PubMed","abstract":"OBJECTIVE: Familial pancreatic cancer (FPC) accounts for approximately 3% of all pancreatic cancer (PC) cases. It has been suggested that high-risk individuals (HRIs) should be offered a screening programme.\nAIM: To evaluate the diagnostic yield of a prospective screening programme in HRIs from families with FPC over a period of 5 years.\nMETHODS: HRIs of families with FPC of the National German Familial Pancreatic Cancer Registry (FaPaCa) were counselled and enrolled in a prospective, board-approved PC screening programme. Screening included clinical examination, laboratory tests, endoscopic ultrasound (EUS) and MRI with magnetic resonance cholangiopancreaticography (MRCP) and MR angiography.\nRESULTS: Between June 2002 and December 2007, 76 HRIs of families with FPC took part in the screening programme with a total of 182 examination visits. Twenty-eight patients revealed abnormalities in EUS (n = 25) and/or MR/MRCP (n = 12). In 7 patients fine needle aspiration cytology was performed. Operative pancreatic explorations were performed in 7 individuals, resulting in limited resections in 6 cases. Histopathological examination of the resected specimens showed serous oligocystic adenomas (n = 3), pancreatic intraepithelial neoplasia 1 (PanIN1) lesions with lobular fibrosis (n = 1), PanIN2 lesions (n = 1) and PanIN1 lesion plus a gastric type intraductal papillary mucinous neoplasm (IPMN) (n = 1).\nCONCLUSIONS: In FPC an EUS/MR/MRCP-based screening programme leads to the detection of potential precursor lesions of PC. However, the yield of an extensive screening programme is low, especially since the tumourigenic value of low grade PanIN lesions is not yet defined. Taking into account the enormous psychological stress for the tested individual and the high costs, a general PC screening in HRIs is not justified.","DOI":"10.1136/gut.2008.171611","ISSN":"1468-3288","note":"PMID: 19470496","journalAbbreviation":"Gut","language":"eng","author":[{"family":"Langer","given":"P."},{"family":"Kann","given":"P. H."},{"family":"Fendrich","given":"V."},{"family":"Habbe","given":"N."},{"family":"Schneider","given":"M."},{"family":"Sina","given":"M."},{"family":"Slater","given":"E. P."},{"family":"Heverhagen","given":"J. T."},{"family":"Gress","given":"T. M."},{"family":"Rothmund","given":"M."},{"family":"Bartsch","given":"D. K."}],"issued":{"date-parts":[["2009",10]]}}},{"id":"BbVydael/9sdQOJDj","uris":[""],"uri":[""],"itemData":{"id":88,"type":"article-journal","title":"Screening for pancreatic cancer in a high-risk population with serum CA 19-9 and targeted EUS: a feasibility study","container-title":"Gastrointestinal Endoscopy","page":"87-95","volume":"74","issue":"1","source":"PubMed","abstract":"BACKGROUND: Earlier detection of pancreatic adenocarcinoma is needed.\nOBJECTIVE: To determine whether early pancreatic neoplasia can be detected in a high-risk population by using CA 19-9 followed by targeted EUS.\nDESIGN: Prospective cohort study.\nSETTING: Two academic medical centers.\nPATIENTS: Eligible patients met age criteria and had at least 1 first-degree relative with pancreatic adenocarcinoma.\nINTERVENTIONS: A serum CA 19-9 was performed on all patients. EUS was performed if the CA 19-9 level was elevated. FNA of identified lesions was performed. Patients with pancreatic cancer detected by using this screening protocol were compared with patients presenting off-protocol for staging data. Medicare reimbursement rates were used to derive cost data.\nMAIN OUTCOME MEASUREMENTS: Detection of early pancreatic neoplasia.\nRESULTS: A total of 546 patients were enrolled. CA 19-9 was elevated in 27 patients (4.9%, 95% CI, 3.2%-7.1%). Neoplastic or malignant findings were detected in 5 patients (0.9%, 95% CI, 0.3%-2.1%), and pancreatic adenocarcinoma in 1 patient (0.2%, 95% CI, 0.005%-1.02%). The patient with pancreatic cancer detected as part of this protocol was 1 of 2 patients presenting to the University of Vermont with stage 1 cancer. The cost to detect 1 pancreatic neoplasia was $8431. The cost to detect 1 pancreatic adenocarcinoma was $41,133.\nLIMITATIONS: The sample size is adequate only to demonstrate the feasibility of this approach.\nCONCLUSIONS: Potentially curative pancreatic adenocarcinoma can be identified with this screening protocol. Stage 1 pancreatic cancer is more likely to be detected by using this screening protocol than by using standard means of detection.","DOI":"10.1016/j.gie.2011.03.1235","ISSN":"1097-6779","note":"PMID: 21704809","title-short":"Screening for pancreatic cancer in a high-risk population with serum CA 19-9 and targeted EUS","journalAbbreviation":"Gastrointest. Endosc.","language":"eng","author":[{"family":"Zubarik","given":"Richard"},{"family":"Gordon","given":"Stuart R."},{"family":"Lidofsky","given":"Steven D."},{"family":"Anderson","given":"Scott R."},{"family":"Pipas","given":"J. Marc"},{"family":"Badger","given":"Gary"},{"family":"Ganguly","given":"Eric"},{"family":"Vecchio","given":"James"}],"issued":{"date-parts":[["2011",7]]}}}],"schema":""} [4,9,11–16]. In the remaining 85% of families with no identified germline mutation, familial pancreatic cancer (FPC) is defined by the occurrence of PC in ≥ 2 first-degree relatives or in ≥ 3 relatives whatever the degree of relationship on the same side of the family ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"xISxu7sB","properties":{"formattedCitation":"\\super [4,17]\\nosupersub{}","plainCitation":"[4,17]","noteIndex":0},"citationItems":[{"id":"BbVydael/zZTZnNXC","uris":[""],"uri":[""],"itemData":{"id":36,"type":"article-journal","title":"Refinement of screening for familial pancreatic cancer","container-title":"Gut","page":"1314-1321","volume":"65","issue":"8","source":"PubMed","abstract":"OBJECTIVE: Surveillance programmes are recommended for individuals at risk (IAR) of familial pancreatic cancer (FPC) to detect early pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC). However, the age to begin screening and the optimal screening protocol remain to be determined.\nMETHODS: IAR from non-CDKN2A FPC families underwent annual screening by MRI with endoscopic ultrasonography (EUS) in board-approved prospective screening programmes at three tertiary referral centres. The diagnostic yield according to age and different screening protocols was analysed.\nRESULTS: 253 IAR with a median age of 48 (25-81)?years underwent screening with a median of 3 (1-11) screening visits during a median follow-up of 28 (1-152)?months. 134 (53%) IAR revealed pancreatic lesions on imaging, mostly cystic (94%), on baseline or follow-up screening. Lesions were significantly more often identified in IAR above the age of 45?years (p<0.0001). In 21 IAR who underwent surgery, no significant lesions (PDAC, pancreatic intraepithelial neoplasia (PanIN) 3 lesions, high-grade intraductal papillary mucinous neoplasia (IPMN)) were detected before the age of 50?years. Potentially relevant lesions (multifocal PanIN2 lesions, low/moderate-grade branch-duct IPMNs) occurred also significantly more often after the age of 50?years (13 vs 2, p<0.0004). The diagnostic yield of potentially relevant lesions was not different between screening protocols using annual MRI with EUS (n=98) or annual MRI with EUS every 3rd year (n=198) and between IAR screened at intervals of 12?months (n=180) or IAR that decided to be screened at ≥24?months intervals (n=30).\nCONCLUSIONS: It appears safe to start screening for PDAC in IAR of non-CDKN2a FPC families at the age of 50?years. MRI-based screening supplemented by EUS at baseline and every 3rd year or when changes in MRI occur appears to be efficient.","DOI":"10.1136/gutjnl-2015-311098","ISSN":"1468-3288","note":"PMID: 27222532","journalAbbreviation":"Gut","language":"eng","author":[{"family":"Bartsch","given":"D. K."},{"family":"Slater","given":"E. P."},{"family":"Carrato","given":"A."},{"family":"Ibrahim","given":"I. S."},{"family":"Guillen-Ponce","given":"C."},{"family":"Vasen","given":"H. F. A."},{"family":"Matth?i","given":"E."},{"family":"Earl","given":"J."},{"family":"Jendryschek","given":"F. S."},{"family":"Figiel","given":"J."},{"family":"Steinkamp","given":"M."},{"family":"Ramaswamy","given":"A."},{"family":"Vázquez-Sequeiros","given":"E."},{"family":"Mu?oz-Beltran","given":"M."},{"family":"Montans","given":"J."},{"family":"Mocci","given":"E."},{"family":"Bonsing","given":"B. A."},{"family":"Wasser","given":"M."},{"family":"Kl?ppel","given":"G."},{"family":"Langer","given":"P."},{"family":"Fendrich","given":"V."},{"family":"Gress","given":"T. M."}],"issued":{"date-parts":[["2016"]]}}},{"id":"BbVydael/Cz27nE6J","uris":[""],"uri":[""],"itemData":{"id":17,"type":"article-journal","title":"Evaluating Susceptibility to Pancreatic Cancer: ASCO Clinical Practice Provisional Clinical Opinion Summary","container-title":"Journal of Oncology Practice","page":"108-111","volume":"15","issue":"2","source":"PubMed","DOI":"10.1200/JOP.18.00629","ISSN":"1935-469X","note":"PMID: 30589608","title-short":"Evaluating Susceptibility to Pancreatic Cancer","journalAbbreviation":"J Oncol Pract","language":"eng","author":[{"family":"Stoffel","given":"Elena M."},{"family":"McKernin","given":"Shannon E."},{"family":"Khorana","given":"Alok A."}],"issued":{"date-parts":[["2019",2]]}}}],"schema":""} [4,17].Pancreatic screening is recommended in high-risk individuals (HRI) to identify early (pre)malignant pancreatic lesions and propose surgical resection with curative intent. The purpose of this screening is to reduce mortality related to PC. While numerous large and retrospective studies have reported on the short-term outcomes of pancreatic screening in HRI, follow-up was generally limited, and hence the magnitude of benefit of pancreatic screening in terms of curative potential remains currently unknown ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"v2nLf4M3","properties":{"formattedCitation":"\\super [11,12,17\\uc0\\u8211{}19]\\nosupersub{}","plainCitation":"[11,12,17–19]","noteIndex":0},"citationItems":[{"id":"BbVydael/iMJ7y1A2","uris":[""],"uri":[""],"itemData":{"id":33,"type":"article-journal","title":"Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma: a patient-level meta-analysis and proposition of the Beaujon score","container-title":"United European Gastroenterology Journal","page":"205064061882491","source":"Crossref","DOI":"10.1177/2050640618824910","ISSN":"2050-6406, 2050-6414","title-short":"Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma","language":"en","author":[{"family":"Mestier","given":"Louis","non-dropping-particle":"de"},{"family":"Muller","given":"Marie"},{"family":"Cros","given":"Jér?me"},{"family":"Vullierme","given":"Marie-Pierre"},{"family":"Vernerey","given":"Dewi"},{"family":"Maire","given":"Frédérique"},{"family":"Dokmak","given":"Safi"},{"family":"Rebours","given":"Vinciane"},{"family":"Sauvanet","given":"Alain"},{"family":"Lévy","given":"Philippe"},{"family":"Hammel","given":"Pascal"}],"issued":{"date-parts":[["2019",1,12]]}}},{"id":"BbVydael/Y8fwuXm1","uris":[""],"uri":[""],"itemData":{"id":44,"type":"article-journal","title":"Screening for pancreatic neoplasia in high-risk individuals: an EUS-based approach","container-title":"Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association","page":"606-621","volume":"2","issue":"7","source":"PubMed","abstract":"BACKGROUND & AIMS: Relatives of patients with pancreatic cancer and persons with certain inherited syndromes are at increased risk for developing pancreatic cancer. We prospectively evaluated the feasibility of screening for pancreatic neoplasia in high-risk individuals.\nMETHODS: Individuals from familial pancreatic cancer kindreds and a patient with Peutz-Jeghers syndrome underwent screening endoscopic ultrasound (EUS). If the EUS was abnormal, EUS-guided fine-needle aspiration, endoscopic retrograde cholangiopancreatography (ERCP), and spiral computed tomography (CT) were performed. Patients with abnormalities suggesting neoplasia had surgery.\nRESULTS: Thirty-eight patients were studied; 31 (mean age, 58 yr; 42% men) from kindreds with > or =3 affected with pancreatic cancer; 6 from kindreds with 2 affected relatives, 1 was a patient with Peutz-Jeghers syndrome. None had symptoms referable to the pancreas or suggestive of malignancy. Six pancreatic masses were found by EUS: 1 invasive ductal adenocarcinoma, 1 benign intraductal papillary mucinous neoplasm, 2 serous cystadenomas, and 2 nonneoplastic masses. Hence, the diagnostic yield for detecting clinically significant pancreatic neoplasms was 5.3% (2 of 38). The 1 patient with pancreatic cancer was treated and still is alive and disease-free >5 years after surgery. EUS changes similar to those associated with chronic pancreatitis were found, which were more common in patients with a history of regular alcohol intake (P = 0.02), but also occurred in patients who did not consume alcohol. Screening also led to a new diagnosis and treatment of symptomatic upper-gastrointestinal conditions in 18.4% of patients.\nCONCLUSIONS: EUS-based screening of asymptomatic high-risk individuals can detect prevalent resectable pancreatic neoplasia but false-positive diagnoses also occur.","ISSN":"1542-3565","note":"PMID: 15224285","title-short":"Screening for pancreatic neoplasia in high-risk individuals","journalAbbreviation":"Clin. Gastroenterol. Hepatol.","language":"eng","author":[{"family":"Canto","given":"Marcia Irene"},{"family":"Goggins","given":"Michael"},{"family":"Yeo","given":"Charles J."},{"family":"Griffin","given":"Constance"},{"family":"Axilbund","given":"Jennifer E."},{"family":"Brune","given":"Kieran"},{"family":"Ali","given":"Syed Z."},{"family":"Jagannath","given":"Sanjay"},{"family":"Petersen","given":"Gloria M."},{"family":"Fishman","given":"Elliot K."},{"family":"Piantadosi","given":"Steven"},{"family":"Giardiello","given":"Francis M."},{"family":"Hruban","given":"Ralph H."}],"issued":{"date-parts":[["2004",7]]}}},{"id":"BbVydael/Cz27nE6J","uris":[""],"uri":[""],"itemData":{"id":17,"type":"article-journal","title":"Evaluating Susceptibility to Pancreatic Cancer: ASCO Clinical Practice Provisional Clinical Opinion Summary","container-title":"Journal of Oncology Practice","page":"108-111","volume":"15","issue":"2","source":"PubMed","DOI":"10.1200/JOP.18.00629","ISSN":"1935-469X","note":"PMID: 30589608","title-short":"Evaluating Susceptibility to Pancreatic Cancer","journalAbbreviation":"J Oncol Pract","language":"eng","author":[{"family":"Stoffel","given":"Elena M."},{"family":"McKernin","given":"Shannon E."},{"family":"Khorana","given":"Alok A."}],"issued":{"date-parts":[["2019",2]]}}},{"id":"BbVydael/C3zHNTfr","uris":[""],"uri":[""],"itemData":{"id":95,"type":"article-journal","title":"Results of surveillance in individuals at high-risk of pancreatic cancer: A systematic review and meta-analysis","container-title":"United European Gastroenterology Journal","page":"489-499","volume":"6","issue":"4","source":"PubMed","abstract":"Background: Data on surveillance for pancreatic ductal adenocarcinoma (PDAC) in high-risk individuals (HRIs) with \"familial pancreatic cancer\" (FPC) and specific syndromes are limited and heterogeneous.\nObjective: We conducted a systematic review and meta-analysis of PDAC surveillance studies in HRIs.\nMethods: Prevalence of solid/cystic pancreatic lesions and of lesions considered a successful target of surveillance (proven resectable PDAC and high-grade precursors) was pooled across studies. The rate of lesions diagnosed by endoscopic ultrasonography (EUS)/magnetic resonance imaging (MRI) and across different HRI groups was calculated.\nResults: Sixteen studies incorporating 1588 HRIs were included. The pooled prevalence of pancreatic solid and cystic lesions was 5.8% and 20.2%, respectively. The pooled prevalence of patients with lesions considered a successful target of surveillance was 3.3%, being similar to EUS or MRI and varying across subgroups, being 3% in FPC, 4% in hereditary pancreatitis, 5% in familial melanoma, 6.3% in hereditary breast/ovarian cancer, and 12.2% in Peutz-Jeghers syndrome. The pooled estimated rate of lesions considered a successful target of surveillance during follow-up was 5/1000 person-years.\nConclusion: Surveillance programs identify successful target lesions in 3.3% of HRIs with a similar yield of EUS and MRI and an annual risk of 0.5%. A higher rate of target lesions was reported in HRIs with specific DNA mutations.","DOI":"10.1177/2050640617752182","ISSN":"2050-6406","note":"PMID: 29881603\nPMCID: PMC5987280","title-short":"Results of surveillance in individuals at high-risk of pancreatic cancer","journalAbbreviation":"United European Gastroenterol J","language":"eng","author":[{"family":"Signoretti","given":"Marianna"},{"family":"Bruno","given":"Marco J."},{"family":"Zerboni","given":"Giulia"},{"family":"Poley","given":"Jan-Werner"},{"family":"Delle Fave","given":"Gianfranco"},{"family":"Capurso","given":"Gabriele"}],"issued":{"date-parts":[["2018",5]]}}},{"id":"BbVydael/39vT8LTF","uris":[""],"uri":[""],"itemData":{"id":98,"type":"article-journal","title":"Diagnostic Yield From Screening Asymptomatic Individuals at?High Risk for Pancreatic Cancer: A Meta-analysis of Cohort?Studies","container-title":"Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association","page":"41-53","volume":"17","issue":"1","source":"PubMed","abstract":"BACKGROUND & AIMS: There have been few studies of abdominal imaging screening of individuals at high risk for pancreatic cancer (based on family history or genetic variants). We performed a meta-analysis of prospective cohort studies to determine the diagnostic yield and outcomes of abdominal imaging screening for asymptomatic individuals at high risk.\nMETHODS: Through a systematic review of multiple electronic databases and conference proceedings through July 2017, we identified prospective cohort studies (>20 patients) of asymptomatic adults determined to be at high-risk of pancreatic cancer (lifetime risk >5%, including specific genetic-associated conditions) who were screened by endoscopic ultrasound (EUS) and/or magnetic resonance imaging (MRI) to detect pancreatic lesions. Our primary outcome was identification of high-risk pancreatic lesions (high-grade pancreatic intraepithelial neoplasia, high-grade dysplasia, or adenocarcinoma) at initial screening, and overall incidence during follow up. Summary estimates were reported as incidence rates per 100 patient-years.\nRESULTS: We identified 19 studies comprising 7085 individuals at high risk for pancreatic cancer; of these, 1660 patients were evaluated by EUS and/or MRI. Fifty-nine high-risk lesions were identified (43 adenocarcinomas: 28 during the initial exam and 15 during follow-up surveillance) and 257 patients underwent pancreatic surgery. Based on our meta-analysis, the overall diagnostic yield screening for high-risk pancreatic lesions was 0.74 (95% CI, 0.33-1.14), with moderate heterogeneity among studies. The number needed to screen to identify 1 patient with?a high-risk lesion was 135 (95% CI, 88-303). The diagnostic yield was similar for patients with different genetic features that increased risk, and whether patients were screened by EUS or MRI.\nCONCLUSIONS: Based on meta-analysis, 135 patients at high-risk for pancreatic cancer must be screened to identify 1 patient with a high-risk pancreatic lesion. Further studies are needed to determine whether screening reduces mortality and is cost effectiveness for individuals at high-risk of pancreatic cancer.","DOI":"10.1016/j.cgh.2018.04.065","ISSN":"1542-7714","note":"PMID: 29775792","title-short":"Diagnostic Yield From Screening Asymptomatic Individuals at?High Risk for Pancreatic Cancer","journalAbbreviation":"Clin. Gastroenterol. Hepatol.","language":"eng","author":[{"family":"Corral","given":"Juan E."},{"family":"Mareth","given":"Karl F."},{"family":"Riegert-Johnson","given":"Douglas L."},{"family":"Das","given":"Ananya"},{"family":"Wallace","given":"Michael B."}],"issued":{"date-parts":[["2019",1]]}}}],"schema":""} [11,12,17–19]. Additionally, although screening is usually based on yearly magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS), the role of the latter has not been clearly defined. Our goal was to comprehensively review current data on pancreatic screening and follow-up of HRI, with an emphasis on the role of EUS.Objectives and challenges of pancreatic screening in high-risk individualsThe goal of screening in HRI (history of FPC or pathogenic germline mutations +/- family history of PC) is to reduce PC-related mortality by identifying morphological abnormalities that suggest the development of PC at an early and potentially curative stage ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"d6azIpGe","properties":{"formattedCitation":"\\super [11,17\\uc0\\u8211{}19]\\nosupersub{}","plainCitation":"[11,17–19]","noteIndex":0},"citationItems":[{"id":"BbVydael/iMJ7y1A2","uris":[""],"uri":[""],"itemData":{"id":33,"type":"article-journal","title":"Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma: a patient-level meta-analysis and proposition of the Beaujon score","container-title":"United European Gastroenterology Journal","page":"205064061882491","source":"Crossref","DOI":"10.1177/2050640618824910","ISSN":"2050-6406, 2050-6414","title-short":"Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma","language":"en","author":[{"family":"Mestier","given":"Louis","non-dropping-particle":"de"},{"family":"Muller","given":"Marie"},{"family":"Cros","given":"Jér?me"},{"family":"Vullierme","given":"Marie-Pierre"},{"family":"Vernerey","given":"Dewi"},{"family":"Maire","given":"Frédérique"},{"family":"Dokmak","given":"Safi"},{"family":"Rebours","given":"Vinciane"},{"family":"Sauvanet","given":"Alain"},{"family":"Lévy","given":"Philippe"},{"family":"Hammel","given":"Pascal"}],"issued":{"date-parts":[["2019",1,12]]}}},{"id":"BbVydael/Cz27nE6J","uris":[""],"uri":[""],"itemData":{"id":17,"type":"article-journal","title":"Evaluating Susceptibility to Pancreatic Cancer: ASCO Clinical Practice Provisional Clinical Opinion Summary","container-title":"Journal of Oncology Practice","page":"108-111","volume":"15","issue":"2","source":"PubMed","DOI":"10.1200/JOP.18.00629","ISSN":"1935-469X","note":"PMID: 30589608","title-short":"Evaluating Susceptibility to Pancreatic Cancer","journalAbbreviation":"J Oncol Pract","language":"eng","author":[{"family":"Stoffel","given":"Elena M."},{"family":"McKernin","given":"Shannon E."},{"family":"Khorana","given":"Alok A."}],"issued":{"date-parts":[["2019",2]]}}},{"id":"BbVydael/C3zHNTfr","uris":[""],"uri":[""],"itemData":{"id":95,"type":"article-journal","title":"Results of surveillance in individuals at high-risk of pancreatic cancer: A systematic review and meta-analysis","container-title":"United European Gastroenterology Journal","page":"489-499","volume":"6","issue":"4","source":"PubMed","abstract":"Background: Data on surveillance for pancreatic ductal adenocarcinoma (PDAC) in high-risk individuals (HRIs) with \"familial pancreatic cancer\" (FPC) and specific syndromes are limited and heterogeneous.\nObjective: We conducted a systematic review and meta-analysis of PDAC surveillance studies in HRIs.\nMethods: Prevalence of solid/cystic pancreatic lesions and of lesions considered a successful target of surveillance (proven resectable PDAC and high-grade precursors) was pooled across studies. The rate of lesions diagnosed by endoscopic ultrasonography (EUS)/magnetic resonance imaging (MRI) and across different HRI groups was calculated.\nResults: Sixteen studies incorporating 1588 HRIs were included. The pooled prevalence of pancreatic solid and cystic lesions was 5.8% and 20.2%, respectively. The pooled prevalence of patients with lesions considered a successful target of surveillance was 3.3%, being similar to EUS or MRI and varying across subgroups, being 3% in FPC, 4% in hereditary pancreatitis, 5% in familial melanoma, 6.3% in hereditary breast/ovarian cancer, and 12.2% in Peutz-Jeghers syndrome. The pooled estimated rate of lesions considered a successful target of surveillance during follow-up was 5/1000 person-years.\nConclusion: Surveillance programs identify successful target lesions in 3.3% of HRIs with a similar yield of EUS and MRI and an annual risk of 0.5%. A higher rate of target lesions was reported in HRIs with specific DNA mutations.","DOI":"10.1177/2050640617752182","ISSN":"2050-6406","note":"PMID: 29881603\nPMCID: PMC5987280","title-short":"Results of surveillance in individuals at high-risk of pancreatic cancer","journalAbbreviation":"United European Gastroenterol J","language":"eng","author":[{"family":"Signoretti","given":"Marianna"},{"family":"Bruno","given":"Marco J."},{"family":"Zerboni","given":"Giulia"},{"family":"Poley","given":"Jan-Werner"},{"family":"Delle Fave","given":"Gianfranco"},{"family":"Capurso","given":"Gabriele"}],"issued":{"date-parts":[["2018",5]]}}},{"id":"BbVydael/39vT8LTF","uris":[""],"uri":[""],"itemData":{"id":98,"type":"article-journal","title":"Diagnostic Yield From Screening Asymptomatic Individuals at?High Risk for Pancreatic Cancer: A Meta-analysis of Cohort?Studies","container-title":"Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association","page":"41-53","volume":"17","issue":"1","source":"PubMed","abstract":"BACKGROUND & AIMS: There have been few studies of abdominal imaging screening of individuals at high risk for pancreatic cancer (based on family history or genetic variants). We performed a meta-analysis of prospective cohort studies to determine the diagnostic yield and outcomes of abdominal imaging screening for asymptomatic individuals at high risk.\nMETHODS: Through a systematic review of multiple electronic databases and conference proceedings through July 2017, we identified prospective cohort studies (>20 patients) of asymptomatic adults determined to be at high-risk of pancreatic cancer (lifetime risk >5%, including specific genetic-associated conditions) who were screened by endoscopic ultrasound (EUS) and/or magnetic resonance imaging (MRI) to detect pancreatic lesions. Our primary outcome was identification of high-risk pancreatic lesions (high-grade pancreatic intraepithelial neoplasia, high-grade dysplasia, or adenocarcinoma) at initial screening, and overall incidence during follow up. Summary estimates were reported as incidence rates per 100 patient-years.\nRESULTS: We identified 19 studies comprising 7085 individuals at high risk for pancreatic cancer; of these, 1660 patients were evaluated by EUS and/or MRI. Fifty-nine high-risk lesions were identified (43 adenocarcinomas: 28 during the initial exam and 15 during follow-up surveillance) and 257 patients underwent pancreatic surgery. Based on our meta-analysis, the overall diagnostic yield screening for high-risk pancreatic lesions was 0.74 (95% CI, 0.33-1.14), with moderate heterogeneity among studies. The number needed to screen to identify 1 patient with?a high-risk lesion was 135 (95% CI, 88-303). The diagnostic yield was similar for patients with different genetic features that increased risk, and whether patients were screened by EUS or MRI.\nCONCLUSIONS: Based on meta-analysis, 135 patients at high-risk for pancreatic cancer must be screened to identify 1 patient with a high-risk pancreatic lesion. Further studies are needed to determine whether screening reduces mortality and is cost effectiveness for individuals at high-risk of pancreatic cancer.","DOI":"10.1016/j.cgh.2018.04.065","ISSN":"1542-7714","note":"PMID: 29775792","title-short":"Diagnostic Yield From Screening Asymptomatic Individuals at?High Risk for Pancreatic Cancer","journalAbbreviation":"Clin. Gastroenterol. Hepatol.","language":"eng","author":[{"family":"Corral","given":"Juan E."},{"family":"Mareth","given":"Karl F."},{"family":"Riegert-Johnson","given":"Douglas L."},{"family":"Das","given":"Ananya"},{"family":"Wallace","given":"Michael B."}],"issued":{"date-parts":[["2019",1]]}}}],"schema":""} [11,17–19]. In a meta-analysis from our group including all HRI treated by surgery reported in the literature, patients without invasive PC who underwent resection of premalignant lesions had no postoperative recurrence compared to those with invasive PC, and their 3-year overall survival was 100% vs 34.6%, respectively (P < 0.001) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"NmRc1Cha","properties":{"formattedCitation":"\\super [11]\\nosupersub{}","plainCitation":"[11]","noteIndex":0},"citationItems":[{"id":"BbVydael/iMJ7y1A2","uris":[""],"uri":[""],"itemData":{"id":33,"type":"article-journal","title":"Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma: a patient-level meta-analysis and proposition of the Beaujon score","container-title":"United European Gastroenterology Journal","page":"205064061882491","source":"Crossref","DOI":"10.1177/2050640618824910","ISSN":"2050-6406, 2050-6414","title-short":"Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma","language":"en","author":[{"family":"Mestier","given":"Louis","non-dropping-particle":"de"},{"family":"Muller","given":"Marie"},{"family":"Cros","given":"Jér?me"},{"family":"Vullierme","given":"Marie-Pierre"},{"family":"Vernerey","given":"Dewi"},{"family":"Maire","given":"Frédérique"},{"family":"Dokmak","given":"Safi"},{"family":"Rebours","given":"Vinciane"},{"family":"Sauvanet","given":"Alain"},{"family":"Lévy","given":"Philippe"},{"family":"Hammel","given":"Pascal"}],"issued":{"date-parts":[["2019",1,12]]}}}],"schema":""} [11]. The lifetime risk of PC in HRI (with germline mutations or FPC) is estimated to be between 1% and 50% depending on the underlying predisposition and the number of affected relatives ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"Q6bsEOIi","properties":{"formattedCitation":"\\super [12,17,20]\\nosupersub{}","plainCitation":"[12,17,20]","noteIndex":0},"citationItems":[{"id":"BbVydael/Y8fwuXm1","uris":[""],"uri":[""],"itemData":{"id":44,"type":"article-journal","title":"Screening for pancreatic neoplasia in high-risk individuals: an EUS-based approach","container-title":"Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association","page":"606-621","volume":"2","issue":"7","source":"PubMed","abstract":"BACKGROUND & AIMS: Relatives of patients with pancreatic cancer and persons with certain inherited syndromes are at increased risk for developing pancreatic cancer. We prospectively evaluated the feasibility of screening for pancreatic neoplasia in high-risk individuals.\nMETHODS: Individuals from familial pancreatic cancer kindreds and a patient with Peutz-Jeghers syndrome underwent screening endoscopic ultrasound (EUS). If the EUS was abnormal, EUS-guided fine-needle aspiration, endoscopic retrograde cholangiopancreatography (ERCP), and spiral computed tomography (CT) were performed. Patients with abnormalities suggesting neoplasia had surgery.\nRESULTS: Thirty-eight patients were studied; 31 (mean age, 58 yr; 42% men) from kindreds with > or =3 affected with pancreatic cancer; 6 from kindreds with 2 affected relatives, 1 was a patient with Peutz-Jeghers syndrome. None had symptoms referable to the pancreas or suggestive of malignancy. Six pancreatic masses were found by EUS: 1 invasive ductal adenocarcinoma, 1 benign intraductal papillary mucinous neoplasm, 2 serous cystadenomas, and 2 nonneoplastic masses. Hence, the diagnostic yield for detecting clinically significant pancreatic neoplasms was 5.3% (2 of 38). The 1 patient with pancreatic cancer was treated and still is alive and disease-free >5 years after surgery. EUS changes similar to those associated with chronic pancreatitis were found, which were more common in patients with a history of regular alcohol intake (P = 0.02), but also occurred in patients who did not consume alcohol. Screening also led to a new diagnosis and treatment of symptomatic upper-gastrointestinal conditions in 18.4% of patients.\nCONCLUSIONS: EUS-based screening of asymptomatic high-risk individuals can detect prevalent resectable pancreatic neoplasia but false-positive diagnoses also occur.","ISSN":"1542-3565","note":"PMID: 15224285","title-short":"Screening for pancreatic neoplasia in high-risk individuals","journalAbbreviation":"Clin. Gastroenterol. Hepatol.","language":"eng","author":[{"family":"Canto","given":"Marcia Irene"},{"family":"Goggins","given":"Michael"},{"family":"Yeo","given":"Charles J."},{"family":"Griffin","given":"Constance"},{"family":"Axilbund","given":"Jennifer E."},{"family":"Brune","given":"Kieran"},{"family":"Ali","given":"Syed Z."},{"family":"Jagannath","given":"Sanjay"},{"family":"Petersen","given":"Gloria M."},{"family":"Fishman","given":"Elliot K."},{"family":"Piantadosi","given":"Steven"},{"family":"Giardiello","given":"Francis M."},{"family":"Hruban","given":"Ralph H."}],"issued":{"date-parts":[["2004",7]]}}},{"id":"BbVydael/Cz27nE6J","uris":[""],"uri":[""],"itemData":{"id":17,"type":"article-journal","title":"Evaluating Susceptibility to Pancreatic Cancer: ASCO Clinical Practice Provisional Clinical Opinion Summary","container-title":"Journal of Oncology Practice","page":"108-111","volume":"15","issue":"2","source":"PubMed","DOI":"10.1200/JOP.18.00629","ISSN":"1935-469X","note":"PMID: 30589608","title-short":"Evaluating Susceptibility to Pancreatic Cancer","journalAbbreviation":"J Oncol Pract","language":"eng","author":[{"family":"Stoffel","given":"Elena M."},{"family":"McKernin","given":"Shannon E."},{"family":"Khorana","given":"Alok A."}],"issued":{"date-parts":[["2019",2]]}}},{"id":"BbVydael/AeZRjHj7","uris":[""],"uri":[""],"itemData":{"id":122,"type":"article-journal","title":"Pancreatic Cancer Screening","container-title":"Current Treatment Options in Gastroenterology","page":"562-575","volume":"15","issue":"4","source":"PubMed","abstract":"PURPOSE OF REVIEW: This review describes the rationale for pancreatic cancer screening, outlines groups that are at elevated risk for pancreatic cancer, and summarizes the relative risk in each setting. We also review the methods available for performing pancreatic cancer screening and the recommended screening intervals.\nRECENT FINDINGS: Several genetic mutations have been identified that increase the risk for pancreatic cancer. Most are rare, however, and at-risk individuals are most often those with a strong family history of pancreatic cancer (with multiple family members affected) but no identifiable genetic mutation. Known genetic syndromes that increase the risk for pancreatic cancer include hereditary pancreatitis, familial atypical mole and multiple melanoma, Peutz-Jeghers syndrome, Lynch syndrome, BRCA mutations, and Li-Fraumeni syndrome. Genetic testing should be performed in conjunction with genetic counseling, and testing of an affected family member is preferred if possible.The goal of pancreatic cancer screening is to identify pancreatic cancer at an early, curable stage or, ideally, to identify precancerous lesions that can be resected to prevent the development of cancer. Imaging can be performed with either endoscopic ultrasound (EUS) or magnetic resonance cholangiopancreatography (MRCP). These techniques are generally considered to be complementary, although an advantage of EUS is that cysts or solid lesions can be sampled at the time of the procedure. Published results of small cohorts of high-risk patients in pancreatic cancer screening programs have demonstrated a high prevalence of small cystic lesions identified on EUS or MRCP, which often represent side-branch intraductal papillary mucinous neoplasms (IPMN). Knowledge of conditions and syndromes that increase pancreatic cancer risk allows one to identify those patients that may benefit from pancreatic cancer screening. As we gather evidence from large, international, multicenter cohorts of patients at high-risk for pancreatic cancer who are undergoing screening and as our understanding of the genetic underpinnings of pancreatic cancer improve, recommendations on screening will continue to be refined.","DOI":"10.1007/s11938-017-0149-8","ISSN":"1092-8472","note":"PMID: 28879469","journalAbbreviation":"Curr Treat Options Gastroenterol","language":"eng","author":[{"family":"Das","given":"Koushik K."},{"family":"Early","given":"Dayna"}],"issued":{"date-parts":[["2017",12]]}}}],"schema":""} [12,17,20]. Table 1 presents the risk by mutations and their frequency in inherited cancers. Thus, HRI are theoretically good candidates for pancreatic screening. The first challenge of PC screening is the effective identification of good candidates, specifically, individuals with a theoretical risk threshold, arbitrarily set at 5%, of developing PC in their lifetime. Signoretti et al ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"e1JBsfpj","properties":{"formattedCitation":"\\super [18,21]\\nosupersub{}","plainCitation":"[18,21]","noteIndex":0},"citationItems":[{"id":"BbVydael/C3zHNTfr","uris":[""],"uri":[""],"itemData":{"id":95,"type":"article-journal","title":"Results of surveillance in individuals at high-risk of pancreatic cancer: A systematic review and meta-analysis","container-title":"United European Gastroenterology Journal","page":"489-499","volume":"6","issue":"4","source":"PubMed","abstract":"Background: Data on surveillance for pancreatic ductal adenocarcinoma (PDAC) in high-risk individuals (HRIs) with \"familial pancreatic cancer\" (FPC) and specific syndromes are limited and heterogeneous.\nObjective: We conducted a systematic review and meta-analysis of PDAC surveillance studies in HRIs.\nMethods: Prevalence of solid/cystic pancreatic lesions and of lesions considered a successful target of surveillance (proven resectable PDAC and high-grade precursors) was pooled across studies. The rate of lesions diagnosed by endoscopic ultrasonography (EUS)/magnetic resonance imaging (MRI) and across different HRI groups was calculated.\nResults: Sixteen studies incorporating 1588 HRIs were included. The pooled prevalence of pancreatic solid and cystic lesions was 5.8% and 20.2%, respectively. The pooled prevalence of patients with lesions considered a successful target of surveillance was 3.3%, being similar to EUS or MRI and varying across subgroups, being 3% in FPC, 4% in hereditary pancreatitis, 5% in familial melanoma, 6.3% in hereditary breast/ovarian cancer, and 12.2% in Peutz-Jeghers syndrome. The pooled estimated rate of lesions considered a successful target of surveillance during follow-up was 5/1000 person-years.\nConclusion: Surveillance programs identify successful target lesions in 3.3% of HRIs with a similar yield of EUS and MRI and an annual risk of 0.5%. A higher rate of target lesions was reported in HRIs with specific DNA mutations.","DOI":"10.1177/2050640617752182","ISSN":"2050-6406","note":"PMID: 29881603\nPMCID: PMC5987280","title-short":"Results of surveillance in individuals at high-risk of pancreatic cancer","journalAbbreviation":"United European Gastroenterol J","language":"eng","author":[{"family":"Signoretti","given":"Marianna"},{"family":"Bruno","given":"Marco J."},{"family":"Zerboni","given":"Giulia"},{"family":"Poley","given":"Jan-Werner"},{"family":"Delle Fave","given":"Gianfranco"},{"family":"Capurso","given":"Gabriele"}],"issued":{"date-parts":[["2018",5]]}}},{"id":"BbVydael/8RCXyXU5","uris":[""],"uri":[""],"itemData":{"id":349,"type":"article-journal","title":"Pathology analysis reveals that dysplastic pancreatic ductal lesions are frequent in patients with hereditary pancreatitis","container-title":"Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association","page":"206-212","volume":"8","issue":"2","source":"PubMed","abstract":"BACKGROUND & AIMS: Hereditary pancreatitis (HP) is a risk factor for pancreatic adenocarcinoma. We performed a retrospective, multicenter study to characterize and evaluate the frequency of pancreatic intraepithelial neoplasia (PanIN) and to describe the characteristics of fibrosis in pancreatic surgical specimens from patients with HP.\nMETHODS: Samples from partial pancreatectomies (n = 13) of patients with HP complications (n = 12; 7 males; mean age, 24 y; 1 patient underwent 2 surgeries over 16 years) were analyzed by histologic and immunohistologic analyses; patients with suspected or proven pancreatic adenocarcinoma were excluded. HP diagnosis was confirmed by analysis of PRSS1 mutations. Dysplastic lesions were described according to the PanIN classification.\nRESULTS: Eleven patients were found to have the R122H mutation in PRSS1 and 1 patient was found to have the N29I mutation in PRSS1. Fifty-one PanIN lesions were observed in 10 specimens (77%): PanIN lesions 1a, 1b, 2, and 3 were observed in 8, 5, 8, and 5 specimens, respectively. The median number of PanIN lesions was 3.5 for each specimen. The density of the lesions was 2.6 per 10 cm(2). The size of lesions was greater than 0.5 mm in 55% of the samples. Two patients with PanIN-3 developed pancreatic cancer, 18 months and 44 years after surgery.\nCONCLUSIONS: PanIN lesions are frequent, severe, and occur early in the course of HP. Among patients with PanINs, 50% had PanIN-3 lesions. Pancreatectomy could be considered as a prophylactic against pancreatic cancer in patients with high-grade dysplasia.","DOI":"10.1016/j.cgh.2009.09.009","ISSN":"1542-7714","note":"PMID: 19765677","journalAbbreviation":"Clin. Gastroenterol. Hepatol.","language":"eng","author":[{"family":"Rebours","given":"Vinciane"},{"family":"Lévy","given":"Philippe"},{"family":"Mosnier","given":"Jean-Fran?ois"},{"family":"Scoazec","given":"Jean-Yves"},{"family":"Soubeyrand","given":"Marie-Sophie"},{"family":"Fléjou","given":"Jean-Fran?ois"},{"family":"Turlin","given":"Bruno"},{"family":"Hammel","given":"Pascal"},{"family":"Ruszniewski","given":"Philippe"},{"family":"Bedossa","given":"Pierre"},{"family":"Couvelard","given":"Anne"}],"issued":{"date-parts":[["2010",2]]}}}],"schema":""} [18,21] have shown that the identification of (pre)malignant lesions varies depending on the genetic subgroup (3% in familial PC, 5% in FAMM syndrome, 6.3% in hereditary breast/ovarian cancer, and 12.2% in Peutz-Jeghers syndrome), while it was 42% in patients with hereditary pancreatitis who have the PRSS1 mutation. Corral et al ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"eTUICHxT","properties":{"formattedCitation":"\\super [19]\\nosupersub{}","plainCitation":"[19]","noteIndex":0},"citationItems":[{"id":"BbVydael/39vT8LTF","uris":[""],"uri":[""],"itemData":{"id":98,"type":"article-journal","title":"Diagnostic Yield From Screening Asymptomatic Individuals at?High Risk for Pancreatic Cancer: A Meta-analysis of Cohort?Studies","container-title":"Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association","page":"41-53","volume":"17","issue":"1","source":"PubMed","abstract":"BACKGROUND & AIMS: There have been few studies of abdominal imaging screening of individuals at high risk for pancreatic cancer (based on family history or genetic variants). We performed a meta-analysis of prospective cohort studies to determine the diagnostic yield and outcomes of abdominal imaging screening for asymptomatic individuals at high risk.\nMETHODS: Through a systematic review of multiple electronic databases and conference proceedings through July 2017, we identified prospective cohort studies (>20 patients) of asymptomatic adults determined to be at high-risk of pancreatic cancer (lifetime risk >5%, including specific genetic-associated conditions) who were screened by endoscopic ultrasound (EUS) and/or magnetic resonance imaging (MRI) to detect pancreatic lesions. Our primary outcome was identification of high-risk pancreatic lesions (high-grade pancreatic intraepithelial neoplasia, high-grade dysplasia, or adenocarcinoma) at initial screening, and overall incidence during follow up. Summary estimates were reported as incidence rates per 100 patient-years.\nRESULTS: We identified 19 studies comprising 7085 individuals at high risk for pancreatic cancer; of these, 1660 patients were evaluated by EUS and/or MRI. Fifty-nine high-risk lesions were identified (43 adenocarcinomas: 28 during the initial exam and 15 during follow-up surveillance) and 257 patients underwent pancreatic surgery. Based on our meta-analysis, the overall diagnostic yield screening for high-risk pancreatic lesions was 0.74 (95% CI, 0.33-1.14), with moderate heterogeneity among studies. The number needed to screen to identify 1 patient with?a high-risk lesion was 135 (95% CI, 88-303). The diagnostic yield was similar for patients with different genetic features that increased risk, and whether patients were screened by EUS or MRI.\nCONCLUSIONS: Based on meta-analysis, 135 patients at high-risk for pancreatic cancer must be screened to identify 1 patient with a high-risk pancreatic lesion. Further studies are needed to determine whether screening reduces mortality and is cost effectiveness for individuals at high-risk of pancreatic cancer.","DOI":"10.1016/j.cgh.2018.04.065","ISSN":"1542-7714","note":"PMID: 29775792","title-short":"Diagnostic Yield From Screening Asymptomatic Individuals at?High Risk for Pancreatic Cancer","journalAbbreviation":"Clin. Gastroenterol. Hepatol.","language":"eng","author":[{"family":"Corral","given":"Juan E."},{"family":"Mareth","given":"Karl F."},{"family":"Riegert-Johnson","given":"Douglas L."},{"family":"Das","given":"Ananya"},{"family":"Wallace","given":"Michael B."}],"issued":{"date-parts":[["2019",1]]}}}],"schema":""} [19] estimated that 135 patients needed to be screened to successfully identify 1 patient with?a target lesion (high-risk lesion or PC) (95%CI: 88-303). This low rate was highly questionable, however, due to the very short follow-up period (3.3 years on average) reported in the studies ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"qKdW90cv","properties":{"formattedCitation":"\\super [22]\\nosupersub{}","plainCitation":"[22]","noteIndex":0},"citationItems":[{"id":"BbVydael/VeQTsQWK","uris":[""],"uri":[""],"itemData":{"id":351,"type":"article-journal","title":"Distant metastasis occurs late during the genetic evolution of pancreatic cancer","container-title":"Nature","page":"1114-1117","volume":"467","issue":"7319","source":"PubMed","abstract":"Metastasis, the dissemination and growth of neoplastic cells in an organ distinct from that in which they originated, is the most common cause of death in cancer patients. This is particularly true for pancreatic cancers, where most patients are diagnosed with metastatic disease and few show a sustained response to chemotherapy or radiation therapy. Whether the dismal prognosis of patients with pancreatic cancer compared to patients with other types of cancer is a result of late diagnosis or early dissemination of disease to distant organs is not known. Here we rely on data generated by sequencing the genomes of seven pancreatic cancer metastases to evaluate the clonal relationships among primary and metastatic cancers. We find that clonal populations that give rise to distant metastases are represented within the primary carcinoma, but these clones are genetically evolved from the original parental, non-metastatic clone. Thus, genetic heterogeneity of metastases reflects that within the primary carcinoma. A quantitative analysis of the timing of the genetic evolution of pancreatic cancer was performed, indicating at least a decade between the occurrence of the initiating mutation and the birth of the parental, non-metastatic founder cell. At least five more years are required for the acquisition of metastatic ability and patients die an average of two years thereafter. These data provide novel insights into the genetic features underlying pancreatic cancer progression and define a broad time window of opportunity for early detection to prevent deaths from metastatic disease.","DOI":"10.1038/nature09515","ISSN":"1476-4687","note":"PMID: 20981102\nPMCID: PMC3148940","journalAbbreviation":"Nature","language":"eng","author":[{"family":"Yachida","given":"Shinichi"},{"family":"Jones","given":"Si?n"},{"family":"Bozic","given":"Ivana"},{"family":"Antal","given":"Tibor"},{"family":"Leary","given":"Rebecca"},{"family":"Fu","given":"Baojin"},{"family":"Kamiyama","given":"Mihoko"},{"family":"Hruban","given":"Ralph H."},{"family":"Eshleman","given":"James R."},{"family":"Nowak","given":"Martin A."},{"family":"Velculescu","given":"Victor E."},{"family":"Kinzler","given":"Kenneth W."},{"family":"Vogelstein","given":"Bert"},{"family":"Iacobuzio-Donahue","given":"Christine A."}],"issued":{"date-parts":[["2010",10,28]]}}}],"schema":""} [22]. Indeed, it contrasts with the delay that was estimated for a premalignant lesion to transform into invasive cancer (11 years) and does not enable the drawing of conclusions regarding the global yield of pancreatic screening in HRI.Relevant imaging pancreatic abnormalities are identified at imaging in approximately 50% of HRI, but this figure is difficult to interpret as there have been too few correlations of these imaging abnormalities with pathological examination due to the limited number of operated patients ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"jN9VNMG6","properties":{"formattedCitation":"\\super [11,18,23]\\nosupersub{}","plainCitation":"[11,18,23]","noteIndex":0},"citationItems":[{"id":"BbVydael/iMJ7y1A2","uris":[""],"uri":[""],"itemData":{"id":33,"type":"article-journal","title":"Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma: a patient-level meta-analysis and proposition of the Beaujon score","container-title":"United European Gastroenterology Journal","page":"205064061882491","source":"Crossref","DOI":"10.1177/2050640618824910","ISSN":"2050-6406, 2050-6414","title-short":"Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma","language":"en","author":[{"family":"Mestier","given":"Louis","non-dropping-particle":"de"},{"family":"Muller","given":"Marie"},{"family":"Cros","given":"Jér?me"},{"family":"Vullierme","given":"Marie-Pierre"},{"family":"Vernerey","given":"Dewi"},{"family":"Maire","given":"Frédérique"},{"family":"Dokmak","given":"Safi"},{"family":"Rebours","given":"Vinciane"},{"family":"Sauvanet","given":"Alain"},{"family":"Lévy","given":"Philippe"},{"family":"Hammel","given":"Pascal"}],"issued":{"date-parts":[["2019",1,12]]}}},{"id":"BbVydael/C3zHNTfr","uris":[""],"uri":[""],"itemData":{"id":95,"type":"article-journal","title":"Results of surveillance in individuals at high-risk of pancreatic cancer: A systematic review and meta-analysis","container-title":"United European Gastroenterology Journal","page":"489-499","volume":"6","issue":"4","source":"PubMed","abstract":"Background: Data on surveillance for pancreatic ductal adenocarcinoma (PDAC) in high-risk individuals (HRIs) with \"familial pancreatic cancer\" (FPC) and specific syndromes are limited and heterogeneous.\nObjective: We conducted a systematic review and meta-analysis of PDAC surveillance studies in HRIs.\nMethods: Prevalence of solid/cystic pancreatic lesions and of lesions considered a successful target of surveillance (proven resectable PDAC and high-grade precursors) was pooled across studies. The rate of lesions diagnosed by endoscopic ultrasonography (EUS)/magnetic resonance imaging (MRI) and across different HRI groups was calculated.\nResults: Sixteen studies incorporating 1588 HRIs were included. The pooled prevalence of pancreatic solid and cystic lesions was 5.8% and 20.2%, respectively. The pooled prevalence of patients with lesions considered a successful target of surveillance was 3.3%, being similar to EUS or MRI and varying across subgroups, being 3% in FPC, 4% in hereditary pancreatitis, 5% in familial melanoma, 6.3% in hereditary breast/ovarian cancer, and 12.2% in Peutz-Jeghers syndrome. The pooled estimated rate of lesions considered a successful target of surveillance during follow-up was 5/1000 person-years.\nConclusion: Surveillance programs identify successful target lesions in 3.3% of HRIs with a similar yield of EUS and MRI and an annual risk of 0.5%. A higher rate of target lesions was reported in HRIs with specific DNA mutations.","DOI":"10.1177/2050640617752182","ISSN":"2050-6406","note":"PMID: 29881603\nPMCID: PMC5987280","title-short":"Results of surveillance in individuals at high-risk of pancreatic cancer","journalAbbreviation":"United European Gastroenterol J","language":"eng","author":[{"family":"Signoretti","given":"Marianna"},{"family":"Bruno","given":"Marco J."},{"family":"Zerboni","given":"Giulia"},{"family":"Poley","given":"Jan-Werner"},{"family":"Delle Fave","given":"Gianfranco"},{"family":"Capurso","given":"Gabriele"}],"issued":{"date-parts":[["2018",5]]}}},{"id":"BbVydael/NFPiCpG1","uris":[""],"uri":[""],"itemData":{"id":46,"type":"article-journal","title":"Screening for early pancreatic neoplasia in high-risk individuals: a prospective controlled study","container-title":"Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association","page":"766-781; quiz 665","volume":"4","issue":"6","source":"PubMed","abstract":"BACKGROUND & AIMS: Individuals with a strong family history of pancreatic cancer and persons with Peutz-Jeghers syndrome (PJS) have an increased risk for pancreatic cancer. This study screened for early pancreatic neoplasia and compared the pancreatic abnormalities in high-risk individuals and control subjects.\nMETHODS: High-risk individuals with PJS or a strong family history of pancreatic cancer were prospectively evaluated with baseline and 12-month computed tomography (CT) scan and endoscopic ultrasonography (EUS). If EUS was abnormal, EUS-fine-needle aspiration and endoscopic retrograde cholangiopancreatography (ERCP) were performed. Surgery was offered to patients with potentially neoplastic lesions. Radiologic findings and pathologic diagnoses were compared. Patients undergoing EUS and/or ERCP for benign non-pancreatic indications were concurrently enrolled as control subjects.\nRESULTS: Seventy-eight high-risk patients (72 from familial pancreatic cancer kindreds, 6 PJS) and 149 control patients were studied. To date, 8 patients with pancreatic neoplasia have been confirmed by surgery or fine-needle aspiration (10% yield of screening); 6 patients had 8 benign intraductal papillary mucinous neoplasms (IPMNs), 1 had an IPMN that progressed to invasive ductal adenocarcinoma, and 1 had pancreatic intraepithelial neoplasia. EUS and CT also diagnosed 3 patients with 5 extrapancreatic neoplasms. At EUS and ERCP abnormalities suggestive of chronic pancreatitis were more common in high-risk patients than in control subjects.\nCONCLUSIONS: Screening EUS and CT diagnosed significant asymptomatic pancreatic and extrapancreatic neoplasms in high-risk individuals. IPMN should be considered a part of the phenotype of familial pancreatic cancer. Abnormalities suggestive of chronic pancreatitis are identified more commonly at EUS and ERCP in high-risk individuals.","DOI":"10.1016/j.cgh.2006.02.005","ISSN":"1542-3565","note":"PMID: 16682259","title-short":"Screening for early pancreatic neoplasia in high-risk individuals","journalAbbreviation":"Clin. Gastroenterol. Hepatol.","language":"eng","author":[{"family":"Canto","given":"Marcia Irene"},{"family":"Goggins","given":"Michael"},{"family":"Hruban","given":"Ralph H."},{"family":"Petersen","given":"Gloria M."},{"family":"Giardiello","given":"Francis M."},{"family":"Yeo","given":"Charles"},{"family":"Fishman","given":"Elliott K."},{"family":"Brune","given":"Kieran"},{"family":"Axilbund","given":"Jennifer"},{"family":"Griffin","given":"Constance"},{"family":"Ali","given":"Syed"},{"family":"Richman","given":"Jeffrey"},{"family":"Jagannath","given":"Sanjay"},{"family":"Kantsevoy","given":"Sergey V."},{"family":"Kalloo","given":"Anthony N."}],"issued":{"date-parts":[["2006",6]]}}}],"schema":""} [11,18,23]. Another challenge of pancreatic screening is to identify and use the most appropriate screening techniques. Ideally, this would be the least invasive and reproducible technique that identifies the greatest number of premalignant lesions and that is the most acceptable for the patient. The ultimate goal of this approach is to propose surgical resection of premalignant lesions [such as pancreatic intraepithelial neoplasia (PanIN) or intraductal papillary mucinous neoplasms (IPMN) with high-grade dysplasia (HGD)] or even early-stage invasive PC, which are found in approximately 3%-5% of HRI ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"bWGzrjy0","properties":{"formattedCitation":"\\super [11,19]\\nosupersub{}","plainCitation":"[11,19]","noteIndex":0},"citationItems":[{"id":"BbVydael/iMJ7y1A2","uris":[""],"uri":[""],"itemData":{"id":33,"type":"article-journal","title":"Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma: a patient-level meta-analysis and proposition of the Beaujon score","container-title":"United European Gastroenterology Journal","page":"205064061882491","source":"Crossref","DOI":"10.1177/2050640618824910","ISSN":"2050-6406, 2050-6414","title-short":"Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma","language":"en","author":[{"family":"Mestier","given":"Louis","non-dropping-particle":"de"},{"family":"Muller","given":"Marie"},{"family":"Cros","given":"Jér?me"},{"family":"Vullierme","given":"Marie-Pierre"},{"family":"Vernerey","given":"Dewi"},{"family":"Maire","given":"Frédérique"},{"family":"Dokmak","given":"Safi"},{"family":"Rebours","given":"Vinciane"},{"family":"Sauvanet","given":"Alain"},{"family":"Lévy","given":"Philippe"},{"family":"Hammel","given":"Pascal"}],"issued":{"date-parts":[["2019",1,12]]}}},{"id":"BbVydael/39vT8LTF","uris":[""],"uri":[""],"itemData":{"id":98,"type":"article-journal","title":"Diagnostic Yield From Screening Asymptomatic Individuals at?High Risk for Pancreatic Cancer: A Meta-analysis of Cohort?Studies","container-title":"Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association","page":"41-53","volume":"17","issue":"1","source":"PubMed","abstract":"BACKGROUND & AIMS: There have been few studies of abdominal imaging screening of individuals at high risk for pancreatic cancer (based on family history or genetic variants). We performed a meta-analysis of prospective cohort studies to determine the diagnostic yield and outcomes of abdominal imaging screening for asymptomatic individuals at high risk.\nMETHODS: Through a systematic review of multiple electronic databases and conference proceedings through July 2017, we identified prospective cohort studies (>20 patients) of asymptomatic adults determined to be at high-risk of pancreatic cancer (lifetime risk >5%, including specific genetic-associated conditions) who were screened by endoscopic ultrasound (EUS) and/or magnetic resonance imaging (MRI) to detect pancreatic lesions. Our primary outcome was identification of high-risk pancreatic lesions (high-grade pancreatic intraepithelial neoplasia, high-grade dysplasia, or adenocarcinoma) at initial screening, and overall incidence during follow up. Summary estimates were reported as incidence rates per 100 patient-years.\nRESULTS: We identified 19 studies comprising 7085 individuals at high risk for pancreatic cancer; of these, 1660 patients were evaluated by EUS and/or MRI. Fifty-nine high-risk lesions were identified (43 adenocarcinomas: 28 during the initial exam and 15 during follow-up surveillance) and 257 patients underwent pancreatic surgery. Based on our meta-analysis, the overall diagnostic yield screening for high-risk pancreatic lesions was 0.74 (95% CI, 0.33-1.14), with moderate heterogeneity among studies. The number needed to screen to identify 1 patient with?a high-risk lesion was 135 (95% CI, 88-303). The diagnostic yield was similar for patients with different genetic features that increased risk, and whether patients were screened by EUS or MRI.\nCONCLUSIONS: Based on meta-analysis, 135 patients at high-risk for pancreatic cancer must be screened to identify 1 patient with a high-risk pancreatic lesion. Further studies are needed to determine whether screening reduces mortality and is cost effectiveness for individuals at high-risk of pancreatic cancer.","DOI":"10.1016/j.cgh.2018.04.065","ISSN":"1542-7714","note":"PMID: 29775792","title-short":"Diagnostic Yield From Screening Asymptomatic Individuals at?High Risk for Pancreatic Cancer","journalAbbreviation":"Clin. Gastroenterol. Hepatol.","language":"eng","author":[{"family":"Corral","given":"Juan E."},{"family":"Mareth","given":"Karl F."},{"family":"Riegert-Johnson","given":"Douglas L."},{"family":"Das","given":"Ananya"},{"family":"Wallace","given":"Michael B."}],"issued":{"date-parts":[["2019",1]]}}}],"schema":""} [11,19]. Finally, identifying lesions at high risk of (pre)malignancy and operating neither too early (low-grade dysplasia) nor too late (advanced PC) is challenging ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1NoFiECW","properties":{"formattedCitation":"\\super [17]\\nosupersub{}","plainCitation":"[17]","noteIndex":0},"citationItems":[{"id":"BbVydael/Cz27nE6J","uris":[""],"uri":[""],"itemData":{"id":17,"type":"article-journal","title":"Evaluating Susceptibility to Pancreatic Cancer: ASCO Clinical Practice Provisional Clinical Opinion Summary","container-title":"Journal of Oncology Practice","page":"108-111","volume":"15","issue":"2","source":"PubMed","DOI":"10.1200/JOP.18.00629","ISSN":"1935-469X","note":"PMID: 30589608","title-short":"Evaluating Susceptibility to Pancreatic Cancer","journalAbbreviation":"J Oncol Pract","language":"eng","author":[{"family":"Stoffel","given":"Elena M."},{"family":"McKernin","given":"Shannon E."},{"family":"Khorana","given":"Alok A."}],"issued":{"date-parts":[["2019",2]]}}}],"schema":""} [17]. We recently found that an indication for prophylactic pancreatectomy was appropriate (based on identification of HGD or invasive PC) in 42.2% of surgically treated HRI ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"BFVfYcJu","properties":{"formattedCitation":"\\super [11]\\nosupersub{}","plainCitation":"[11]","noteIndex":0},"citationItems":[{"id":"BbVydael/iMJ7y1A2","uris":[""],"uri":[""],"itemData":{"id":33,"type":"article-journal","title":"Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma: a patient-level meta-analysis and proposition of the Beaujon score","container-title":"United European Gastroenterology Journal","page":"205064061882491","source":"Crossref","DOI":"10.1177/2050640618824910","ISSN":"2050-6406, 2050-6414","title-short":"Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma","language":"en","author":[{"family":"Mestier","given":"Louis","non-dropping-particle":"de"},{"family":"Muller","given":"Marie"},{"family":"Cros","given":"Jér?me"},{"family":"Vullierme","given":"Marie-Pierre"},{"family":"Vernerey","given":"Dewi"},{"family":"Maire","given":"Frédérique"},{"family":"Dokmak","given":"Safi"},{"family":"Rebours","given":"Vinciane"},{"family":"Sauvanet","given":"Alain"},{"family":"Lévy","given":"Philippe"},{"family":"Hammel","given":"Pascal"}],"issued":{"date-parts":[["2019",1,12]]}}}],"schema":""} [11]. The factors predicting surgical appropriateness were age > 50 years, presence of a germline mutation and the presence of high-risk radiological pancreatic abnormalities (the presence of “worrisome features”, “high-risk stigmata of malignancy”, or a solid pancreatic mass) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"Pc8CIHLC","properties":{"formattedCitation":"\\super [11]\\nosupersub{}","plainCitation":"[11]","noteIndex":0},"citationItems":[{"id":"BbVydael/iMJ7y1A2","uris":[""],"uri":[""],"itemData":{"id":33,"type":"article-journal","title":"Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma: a patient-level meta-analysis and proposition of the Beaujon score","container-title":"United European Gastroenterology Journal","page":"205064061882491","source":"Crossref","DOI":"10.1177/2050640618824910","ISSN":"2050-6406, 2050-6414","title-short":"Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma","language":"en","author":[{"family":"Mestier","given":"Louis","non-dropping-particle":"de"},{"family":"Muller","given":"Marie"},{"family":"Cros","given":"Jér?me"},{"family":"Vullierme","given":"Marie-Pierre"},{"family":"Vernerey","given":"Dewi"},{"family":"Maire","given":"Frédérique"},{"family":"Dokmak","given":"Safi"},{"family":"Rebours","given":"Vinciane"},{"family":"Sauvanet","given":"Alain"},{"family":"Lévy","given":"Philippe"},{"family":"Hammel","given":"Pascal"}],"issued":{"date-parts":[["2019",1,12]]}}}],"schema":""} [11].What is the best screening modality for high-risk individuals?In the past two decades, management of HRI has evolved and varies from one country to another. Screening should be performed in multidisciplinary teams in referral centres, which have more experience and expertise in screening methods (i.e., EUS and MRI) and in the treatment of invasive PC ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"RcfTPwyn","properties":{"formattedCitation":"\\super [17]\\nosupersub{}","plainCitation":"[17]","noteIndex":0},"citationItems":[{"id":"BbVydael/Cz27nE6J","uris":[""],"uri":[""],"itemData":{"id":17,"type":"article-journal","title":"Evaluating Susceptibility to Pancreatic Cancer: ASCO Clinical Practice Provisional Clinical Opinion Summary","container-title":"Journal of Oncology Practice","page":"108-111","volume":"15","issue":"2","source":"PubMed","DOI":"10.1200/JOP.18.00629","ISSN":"1935-469X","note":"PMID: 30589608","title-short":"Evaluating Susceptibility to Pancreatic Cancer","journalAbbreviation":"J Oncol Pract","language":"eng","author":[{"family":"Stoffel","given":"Elena M."},{"family":"McKernin","given":"Shannon E."},{"family":"Khorana","given":"Alok A."}],"issued":{"date-parts":[["2019",2]]}}}],"schema":""} [17]. A recent meta-analysis estimated that the annual prevalence of high-risk lesions (early invasive PC, IPMN,?or PanIN with?HGD) detected in HRI was 3.3%, corresponding to 5/1000 person-years during follow-up and an individual probability of 0.5% per year ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"zbzyjeSA","properties":{"formattedCitation":"\\super [18]\\nosupersub{}","plainCitation":"[18]","noteIndex":0},"citationItems":[{"id":"BbVydael/C3zHNTfr","uris":[""],"uri":[""],"itemData":{"id":95,"type":"article-journal","title":"Results of surveillance in individuals at high-risk of pancreatic cancer: A systematic review and meta-analysis","container-title":"United European Gastroenterology Journal","page":"489-499","volume":"6","issue":"4","source":"PubMed","abstract":"Background: Data on surveillance for pancreatic ductal adenocarcinoma (PDAC) in high-risk individuals (HRIs) with \"familial pancreatic cancer\" (FPC) and specific syndromes are limited and heterogeneous.\nObjective: We conducted a systematic review and meta-analysis of PDAC surveillance studies in HRIs.\nMethods: Prevalence of solid/cystic pancreatic lesions and of lesions considered a successful target of surveillance (proven resectable PDAC and high-grade precursors) was pooled across studies. The rate of lesions diagnosed by endoscopic ultrasonography (EUS)/magnetic resonance imaging (MRI) and across different HRI groups was calculated.\nResults: Sixteen studies incorporating 1588 HRIs were included. The pooled prevalence of pancreatic solid and cystic lesions was 5.8% and 20.2%, respectively. The pooled prevalence of patients with lesions considered a successful target of surveillance was 3.3%, being similar to EUS or MRI and varying across subgroups, being 3% in FPC, 4% in hereditary pancreatitis, 5% in familial melanoma, 6.3% in hereditary breast/ovarian cancer, and 12.2% in Peutz-Jeghers syndrome. The pooled estimated rate of lesions considered a successful target of surveillance during follow-up was 5/1000 person-years.\nConclusion: Surveillance programs identify successful target lesions in 3.3% of HRIs with a similar yield of EUS and MRI and an annual risk of 0.5%. A higher rate of target lesions was reported in HRIs with specific DNA mutations.","DOI":"10.1177/2050640617752182","ISSN":"2050-6406","note":"PMID: 29881603\nPMCID: PMC5987280","title-short":"Results of surveillance in individuals at high-risk of pancreatic cancer","journalAbbreviation":"United European Gastroenterol J","language":"eng","author":[{"family":"Signoretti","given":"Marianna"},{"family":"Bruno","given":"Marco J."},{"family":"Zerboni","given":"Giulia"},{"family":"Poley","given":"Jan-Werner"},{"family":"Delle Fave","given":"Gianfranco"},{"family":"Capurso","given":"Gabriele"}],"issued":{"date-parts":[["2018",5]]}}}],"schema":""} [18]. The screening of HRI is mainly based on pancreatic morphological imaging [computed tomography (CT) scan, MRI and EUS] ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"yc2aFzjk","properties":{"formattedCitation":"\\super [11,12,18,19]\\nosupersub{}","plainCitation":"[11,12,18,19]","noteIndex":0},"citationItems":[{"id":"BbVydael/iMJ7y1A2","uris":[""],"uri":[""],"itemData":{"id":33,"type":"article-journal","title":"Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma: a patient-level meta-analysis and proposition of the Beaujon score","container-title":"United European Gastroenterology Journal","page":"205064061882491","source":"Crossref","DOI":"10.1177/2050640618824910","ISSN":"2050-6406, 2050-6414","title-short":"Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma","language":"en","author":[{"family":"Mestier","given":"Louis","non-dropping-particle":"de"},{"family":"Muller","given":"Marie"},{"family":"Cros","given":"Jér?me"},{"family":"Vullierme","given":"Marie-Pierre"},{"family":"Vernerey","given":"Dewi"},{"family":"Maire","given":"Frédérique"},{"family":"Dokmak","given":"Safi"},{"family":"Rebours","given":"Vinciane"},{"family":"Sauvanet","given":"Alain"},{"family":"Lévy","given":"Philippe"},{"family":"Hammel","given":"Pascal"}],"issued":{"date-parts":[["2019",1,12]]}}},{"id":"BbVydael/Y8fwuXm1","uris":[""],"uri":[""],"itemData":{"id":44,"type":"article-journal","title":"Screening for pancreatic neoplasia in high-risk individuals: an EUS-based approach","container-title":"Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association","page":"606-621","volume":"2","issue":"7","source":"PubMed","abstract":"BACKGROUND & AIMS: Relatives of patients with pancreatic cancer and persons with certain inherited syndromes are at increased risk for developing pancreatic cancer. We prospectively evaluated the feasibility of screening for pancreatic neoplasia in high-risk individuals.\nMETHODS: Individuals from familial pancreatic cancer kindreds and a patient with Peutz-Jeghers syndrome underwent screening endoscopic ultrasound (EUS). If the EUS was abnormal, EUS-guided fine-needle aspiration, endoscopic retrograde cholangiopancreatography (ERCP), and spiral computed tomography (CT) were performed. Patients with abnormalities suggesting neoplasia had surgery.\nRESULTS: Thirty-eight patients were studied; 31 (mean age, 58 yr; 42% men) from kindreds with > or =3 affected with pancreatic cancer; 6 from kindreds with 2 affected relatives, 1 was a patient with Peutz-Jeghers syndrome. None had symptoms referable to the pancreas or suggestive of malignancy. Six pancreatic masses were found by EUS: 1 invasive ductal adenocarcinoma, 1 benign intraductal papillary mucinous neoplasm, 2 serous cystadenomas, and 2 nonneoplastic masses. Hence, the diagnostic yield for detecting clinically significant pancreatic neoplasms was 5.3% (2 of 38). The 1 patient with pancreatic cancer was treated and still is alive and disease-free >5 years after surgery. EUS changes similar to those associated with chronic pancreatitis were found, which were more common in patients with a history of regular alcohol intake (P = 0.02), but also occurred in patients who did not consume alcohol. Screening also led to a new diagnosis and treatment of symptomatic upper-gastrointestinal conditions in 18.4% of patients.\nCONCLUSIONS: EUS-based screening of asymptomatic high-risk individuals can detect prevalent resectable pancreatic neoplasia but false-positive diagnoses also occur.","ISSN":"1542-3565","note":"PMID: 15224285","title-short":"Screening for pancreatic neoplasia in high-risk individuals","journalAbbreviation":"Clin. Gastroenterol. Hepatol.","language":"eng","author":[{"family":"Canto","given":"Marcia Irene"},{"family":"Goggins","given":"Michael"},{"family":"Yeo","given":"Charles J."},{"family":"Griffin","given":"Constance"},{"family":"Axilbund","given":"Jennifer E."},{"family":"Brune","given":"Kieran"},{"family":"Ali","given":"Syed Z."},{"family":"Jagannath","given":"Sanjay"},{"family":"Petersen","given":"Gloria M."},{"family":"Fishman","given":"Elliot K."},{"family":"Piantadosi","given":"Steven"},{"family":"Giardiello","given":"Francis M."},{"family":"Hruban","given":"Ralph H."}],"issued":{"date-parts":[["2004",7]]}}},{"id":"BbVydael/C3zHNTfr","uris":[""],"uri":[""],"itemData":{"id":95,"type":"article-journal","title":"Results of surveillance in individuals at high-risk of pancreatic cancer: A systematic review and meta-analysis","container-title":"United European Gastroenterology Journal","page":"489-499","volume":"6","issue":"4","source":"PubMed","abstract":"Background: Data on surveillance for pancreatic ductal adenocarcinoma (PDAC) in high-risk individuals (HRIs) with \"familial pancreatic cancer\" (FPC) and specific syndromes are limited and heterogeneous.\nObjective: We conducted a systematic review and meta-analysis of PDAC surveillance studies in HRIs.\nMethods: Prevalence of solid/cystic pancreatic lesions and of lesions considered a successful target of surveillance (proven resectable PDAC and high-grade precursors) was pooled across studies. The rate of lesions diagnosed by endoscopic ultrasonography (EUS)/magnetic resonance imaging (MRI) and across different HRI groups was calculated.\nResults: Sixteen studies incorporating 1588 HRIs were included. The pooled prevalence of pancreatic solid and cystic lesions was 5.8% and 20.2%, respectively. The pooled prevalence of patients with lesions considered a successful target of surveillance was 3.3%, being similar to EUS or MRI and varying across subgroups, being 3% in FPC, 4% in hereditary pancreatitis, 5% in familial melanoma, 6.3% in hereditary breast/ovarian cancer, and 12.2% in Peutz-Jeghers syndrome. The pooled estimated rate of lesions considered a successful target of surveillance during follow-up was 5/1000 person-years.\nConclusion: Surveillance programs identify successful target lesions in 3.3% of HRIs with a similar yield of EUS and MRI and an annual risk of 0.5%. A higher rate of target lesions was reported in HRIs with specific DNA mutations.","DOI":"10.1177/2050640617752182","ISSN":"2050-6406","note":"PMID: 29881603\nPMCID: PMC5987280","title-short":"Results of surveillance in individuals at high-risk of pancreatic cancer","journalAbbreviation":"United European Gastroenterol J","language":"eng","author":[{"family":"Signoretti","given":"Marianna"},{"family":"Bruno","given":"Marco J."},{"family":"Zerboni","given":"Giulia"},{"family":"Poley","given":"Jan-Werner"},{"family":"Delle Fave","given":"Gianfranco"},{"family":"Capurso","given":"Gabriele"}],"issued":{"date-parts":[["2018",5]]}}},{"id":"BbVydael/39vT8LTF","uris":[""],"uri":[""],"itemData":{"id":98,"type":"article-journal","title":"Diagnostic Yield From Screening Asymptomatic Individuals at?High Risk for Pancreatic Cancer: A Meta-analysis of Cohort?Studies","container-title":"Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association","page":"41-53","volume":"17","issue":"1","source":"PubMed","abstract":"BACKGROUND & AIMS: There have been few studies of abdominal imaging screening of individuals at high risk for pancreatic cancer (based on family history or genetic variants). We performed a meta-analysis of prospective cohort studies to determine the diagnostic yield and outcomes of abdominal imaging screening for asymptomatic individuals at high risk.\nMETHODS: Through a systematic review of multiple electronic databases and conference proceedings through July 2017, we identified prospective cohort studies (>20 patients) of asymptomatic adults determined to be at high-risk of pancreatic cancer (lifetime risk >5%, including specific genetic-associated conditions) who were screened by endoscopic ultrasound (EUS) and/or magnetic resonance imaging (MRI) to detect pancreatic lesions. Our primary outcome was identification of high-risk pancreatic lesions (high-grade pancreatic intraepithelial neoplasia, high-grade dysplasia, or adenocarcinoma) at initial screening, and overall incidence during follow up. Summary estimates were reported as incidence rates per 100 patient-years.\nRESULTS: We identified 19 studies comprising 7085 individuals at high risk for pancreatic cancer; of these, 1660 patients were evaluated by EUS and/or MRI. Fifty-nine high-risk lesions were identified (43 adenocarcinomas: 28 during the initial exam and 15 during follow-up surveillance) and 257 patients underwent pancreatic surgery. Based on our meta-analysis, the overall diagnostic yield screening for high-risk pancreatic lesions was 0.74 (95% CI, 0.33-1.14), with moderate heterogeneity among studies. The number needed to screen to identify 1 patient with?a high-risk lesion was 135 (95% CI, 88-303). The diagnostic yield was similar for patients with different genetic features that increased risk, and whether patients were screened by EUS or MRI.\nCONCLUSIONS: Based on meta-analysis, 135 patients at high-risk for pancreatic cancer must be screened to identify 1 patient with a high-risk pancreatic lesion. Further studies are needed to determine whether screening reduces mortality and is cost effectiveness for individuals at high-risk of pancreatic cancer.","DOI":"10.1016/j.cgh.2018.04.065","ISSN":"1542-7714","note":"PMID: 29775792","title-short":"Diagnostic Yield From Screening Asymptomatic Individuals at?High Risk for Pancreatic Cancer","journalAbbreviation":"Clin. Gastroenterol. Hepatol.","language":"eng","author":[{"family":"Corral","given":"Juan E."},{"family":"Mareth","given":"Karl F."},{"family":"Riegert-Johnson","given":"Douglas L."},{"family":"Das","given":"Ananya"},{"family":"Wallace","given":"Michael B."}],"issued":{"date-parts":[["2019",1]]}}}],"schema":""} [11,12,18,19]. For a long time, many studies have suggested that EUS might provide better detection of small solid lesions, while MRI can identify small cystic lesions ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"t1OqsvcB","properties":{"formattedCitation":"\\super [24\\uc0\\u8211{}27]\\nosupersub{}","plainCitation":"[24–27]","noteIndex":0},"citationItems":[{"id":"BbVydael/7YSmGfQJ","uris":[""],"uri":[""],"itemData":{"id":134,"type":"article-journal","title":"Role of EUS in the early detection of small pancreatic cancer","container-title":"Digestive Endoscopy: Official Journal of the Japan Gastroenterological Endoscopy Society","page":"22-25","volume":"23 Suppl 1","source":"PubMed","abstract":"The prognosis of pancreatic cancer is extremely poor as a result of the difficulty in early detection of small pancreatic cancer and the intractable nature of appropriate anti-cancer therapies. Computed tomography (CT) is generally used for initial screening, but imaging sensitivities are generally insufficient to detect small masses. Endoscopic ultrasonography (EUS), in contrast, exhibits higher sensitivity than other imaging modalities for the detection of pancreatic cancers, because of the high resolution of images.\nAIMS: The goal of this study was to evaluate the role of EUS in the early detection of small pancreatic cancer.\nMETHODS: We retrospectively reviewed the Gifu University Hospital EUS database (November 2007 to October 2010), and extracted the data of patients whose aim was to confirm the presence or absence of pancreatic cancer subsequent to no tumor detection by abdominal CT.\nRESULTS: In a 3 year period, 132 patients underwent EUS to confirm the presence or absence of small pancreatic cancer. All patients had previously tested negative for pancreatic mass using abdominal CT, but had showed pancreatic cancer risk factors, including increased serum carcinoembryonic antigen and/or CA 19-9 (n = 106), serum amylase (n = 38), and/or mild to moderate dilation of the main pancreatic duct as determined by imaging (n = 88). EUS detected pancreatic mass in three of these patients. The masses in all three patients were minute (≤10 mm) and their presence was correlated with the detection of mild dilation of the main pancreatic duct in earlier CT scans. Increase of tumor markers was observed in two patients and hyperamylasemia and aggravation of diabetes were observed in one patient.\nCONCLUSIONS: EUS is strongly recommended for early detection of small pancreatic cancer in patients in whom the dilation of the main pancreatic duct was detected in previous imaging tests, with or without increase of pancreatic enzymes or tumor markers.","DOI":"10.1111/j.1443-1661.2011.01113.x","ISSN":"1443-1661","note":"PMID: 21535195","journalAbbreviation":"Dig Endosc","language":"eng","author":[{"family":"Yasuda","given":"Ichiro"},{"family":"Iwashita","given":"Takuji"},{"family":"Doi","given":"Shinpei"},{"family":"Nakashima","given":"Masanori"},{"family":"Moriwaki","given":"Hisataka"}],"issued":{"date-parts":[["2011",5]]}}},{"id":"BbVydael/sxr8Ecxk","uris":[""],"uri":[""],"itemData":{"id":58,"type":"article-journal","title":"Frequent detection of pancreatic lesions in asymptomatic high-risk individuals","container-title":"Gastroenterology","page":"796-804; quiz e14-15","volume":"142","issue":"4","source":"PubMed","abstract":"BACKGROUND & AIMS: The risk of pancreatic cancer is increased in patients with a strong family history of pancreatic cancer or a predisposing germline mutation. Screening can detect curable, noninvasive pancreatic neoplasms, but the optimal imaging approach is not known. We determined the baseline prevalence and characteristics of pancreatic abnormalities using 3 imaging tests to screen asymptomatic, high-risk individuals (HRIs).\nMETHODS: We screened 225 asymptomatic adult HRIs at 5 academic US medical centers once, using computed tomography (CT), magnetic resonance imaging (MRI), and endoscopic ultrasonography (EUS). We compared results in a blinded, independent fashion.\nRESULTS: Ninety-two of 216 HRIs (42%) were found to have at least 1 pancreatic mass (84 cystic, 3 solid) or a dilated pancreatic duct (n = 5) by any of the imaging modalities. Fifty-one of the 84 HRIs with a cyst (60.7%) had multiple lesions, typically small (mean, 0.55 cm; range, 2-39 mm), in multiple locations. The prevalence of pancreatic lesions increased with age; they were detected in 14% of subjects younger than 50 years old, 34% of subjects 50-59 years old, and 53% of subjects 60-69 years old (P < .0001). CT, MRI, and EUS detected a pancreatic abnormality in 11%, 33.3%, and 42.6% of the HRIs, respectively. Among these abnormalities, proven or suspected neoplasms were identified in 85 HRIs (82 intraductal papillary mucinous neoplasms and 3 pancreatic endocrine tumors). Three of 5 HRIs who underwent pancreatic resection had high-grade dysplasia in less than 3 cm intraductal papillary mucinous neoplasms and in multiple intraepithelial neoplasias.\nCONCLUSIONS: Screening of asymptomatic HRIs frequently detects small pancreatic cysts, including curable, noninvasive high-grade neoplasms. EUS and MRI detect pancreatic lesions better than CT.","DOI":"10.1053/j.gastro.2012.01.005","ISSN":"1528-0012","note":"PMID: 22245846\nPMCID: PMC3321068","journalAbbreviation":"Gastroenterology","language":"eng","author":[{"family":"Canto","given":"Marcia Irene"},{"family":"Hruban","given":"Ralph H."},{"family":"Fishman","given":"Elliot K."},{"family":"Kamel","given":"Ihab R."},{"family":"Schulick","given":"Richard"},{"family":"Zhang","given":"Zhe"},{"family":"Topazian","given":"Mark"},{"family":"Takahashi","given":"Naoki"},{"family":"Fletcher","given":"Joel"},{"family":"Petersen","given":"Gloria"},{"family":"Klein","given":"Alison P."},{"family":"Axilbund","given":"Jennifer"},{"family":"Griffin","given":"Constance"},{"family":"Syngal","given":"Sapna"},{"family":"Saltzman","given":"John R."},{"family":"Mortele","given":"Koenraad J."},{"family":"Lee","given":"Jeffrey"},{"family":"Tamm","given":"Eric"},{"family":"Vikram","given":"Raghunandan"},{"family":"Bhosale","given":"Priya"},{"family":"Margolis","given":"Daniel"},{"family":"Farrell","given":"James"},{"family":"Goggins","given":"Michael"},{"literal":"American Cancer of the Pancreas Screening (CAPS) Consortium"}],"issued":{"date-parts":[["2012",4]]}}},{"id":"BbVydael/w0k4vP4h","uris":[""],"uri":[""],"itemData":{"id":113,"type":"article-journal","title":"Methods and outcomes of screening for pancreatic adenocarcinoma in high-risk individuals","container-title":"World Journal of Gastrointestinal Endoscopy","page":"833-842","volume":"7","issue":"9","source":"PubMed","abstract":"Pancreatic ductal adenocarcinoma (PDAC) is a lethal neoplasia, for which secondary prevention (i.e., screening) is advisable for high-risk individuals with \"familiar pancreatic cancer\" and with other specific genetic syndromes (Peutz-Jeghers, p16, BRCA2, PALB and mismatch repair gene mutation carriers). There is limited evidence regarding the accuracy of screening tests, their acceptability, costs and availability, and agreement on whom to treat. Successful target of screening are small resectable PDAC, intraductal papillary mucinous neoplasms with high-grade dysplasia and advanced pancreatic intraepithelial neoplasia. Both magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS) are employed for screening, and the overall yield for pre-malignant or malignant pancreatic lesions is of about 20% with EUS and 14% with MRI/magnetic resonance colangiopancreatography. EUS performs better for solid and MRI for cystic lesions. However, only 2% of these detected lesions can be considered a successful target, and there are insufficient data demonstrating that resection of benign or low grade lesions improves survival. Many patients in the published studies therefore seemed to have received an overtreatment by undergoing surgery. It is crucial to better stratify the risk of malignancy individually, and to better define optimal screening intervals and methods either with computerized tools or molecular biomarkers, possibly in large multicentre studies. At the moment, screening should be carefully performed within research protocols at experienced centres, offering involved individuals medical and psychological advice.","DOI":"10.4253/wjge.v7.i9.833","ISSN":"1948-5190","note":"PMID: 26240684\nPMCID: PMC4515417","journalAbbreviation":"World J Gastrointest Endosc","language":"eng","author":[{"family":"Capurso","given":"Gabriele"},{"family":"Signoretti","given":"Marianna"},{"family":"Valente","given":"Roberto"},{"family":"Arnelo","given":"Urban"},{"family":"Lohr","given":"Matthias"},{"family":"Poley","given":"Jan-Werner"},{"family":"Delle Fave","given":"Gianfranco"},{"family":"Del Chiaro","given":"Marco"}],"issued":{"date-parts":[["2015",7,25]]}}},{"id":"BbVydael/KLfm1MxF","uris":[""],"uri":[""],"itemData":{"id":38,"type":"article-journal","title":"A multicentre comparative prospective blinded analysis of EUS and MRI for screening of pancreatic cancer in high-risk individuals","container-title":"Gut","page":"1505-1513","volume":"65","issue":"9","source":"PubMed","abstract":"OBJECTIVE: Endoscopic ultrasonography (EUS) and MRI are promising tests to detect precursors and early-stage pancreatic ductal adenocarcinoma (PDAC) in high-risk individuals (HRIs). It is unclear which screening technique is to be preferred. We aimed to compare the efficacy of EUS and MRI in their ability to detect clinically relevant lesions in HRI.\nDESIGN: Multicentre prospective study. The results of 139 asymptomatic HRI (>10-fold increased risk) undergoing first-time screening by EUS and MRI are described. Clinically relevant lesions were defined as solid lesions, main duct intraductal papillary mucinous neoplasms and cysts ≥10?mm. Results were compared in a blinded, independent fashion.\nRESULTS: Two solid lesions (mean size 9?mm) and nine cysts ≥10?mm (mean size 17?mm) were detected in nine HRI (6%). Both solid lesions were detected by EUS only and proved to be a stage I PDAC and a multifocal pancreatic intraepithelial neoplasia 2. Of the nine cysts ≥10?mm, six were detected by both imaging techniques and three were detected by MRI only. The agreement between EUS and MRI for the detection of clinically relevant lesions was 55%. Of these clinically relevant lesions detected by both techniques, there was a good agreement for location and size.\nCONCLUSIONS: EUS and/or MRI detected clinically relevant pancreatic lesions in 6% of HRI. Both imaging techniques were complementary rather than interchangeable: contrary to EUS, MRI was found to be very sensitive for the detection of cystic lesions of any size; MRI, however, might have some important limitations with regard to the timely detection of solid lesions.","DOI":"10.1136/gutjnl-2014-308008","ISSN":"1468-3288","note":"PMID: 25986944","journalAbbreviation":"Gut","language":"eng","author":[{"family":"Harinck","given":"F."},{"family":"Konings","given":"I. C. a. W."},{"family":"Kluijt","given":"I."},{"family":"Poley","given":"J. W."},{"family":"Hooft","given":"J. E.","non-dropping-particle":"van"},{"family":"Dullemen","given":"H. M.","non-dropping-particle":"van"},{"family":"Nio","given":"C. Y."},{"family":"Krak","given":"N. C."},{"family":"Hermans","given":"J. J."},{"family":"Aalfs","given":"C. M."},{"family":"Wagner","given":"A."},{"family":"Sijmons","given":"R. H."},{"family":"Biermann","given":"K."},{"family":"Eijck","given":"C. H.","non-dropping-particle":"van"},{"family":"Gouma","given":"D. J."},{"family":"Dijkgraaf","given":"M. G. W."},{"family":"Fockens","given":"P."},{"family":"Bruno","given":"M. J."},{"literal":"Dutch research group on pancreatic cancer surveillance in high-risk individuals"}],"issued":{"date-parts":[["2016"]]}}}],"schema":""} [24–27]. In the study by Canto et al ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"OoQ0nU9q","properties":{"formattedCitation":"\\super [25]\\nosupersub{}","plainCitation":"[25]","noteIndex":0},"citationItems":[{"id":"BbVydael/sxr8Ecxk","uris":[""],"uri":[""],"itemData":{"id":58,"type":"article-journal","title":"Frequent detection of pancreatic lesions in asymptomatic high-risk individuals","container-title":"Gastroenterology","page":"796-804; quiz e14-15","volume":"142","issue":"4","source":"PubMed","abstract":"BACKGROUND & AIMS: The risk of pancreatic cancer is increased in patients with a strong family history of pancreatic cancer or a predisposing germline mutation. Screening can detect curable, noninvasive pancreatic neoplasms, but the optimal imaging approach is not known. We determined the baseline prevalence and characteristics of pancreatic abnormalities using 3 imaging tests to screen asymptomatic, high-risk individuals (HRIs).\nMETHODS: We screened 225 asymptomatic adult HRIs at 5 academic US medical centers once, using computed tomography (CT), magnetic resonance imaging (MRI), and endoscopic ultrasonography (EUS). We compared results in a blinded, independent fashion.\nRESULTS: Ninety-two of 216 HRIs (42%) were found to have at least 1 pancreatic mass (84 cystic, 3 solid) or a dilated pancreatic duct (n = 5) by any of the imaging modalities. Fifty-one of the 84 HRIs with a cyst (60.7%) had multiple lesions, typically small (mean, 0.55 cm; range, 2-39 mm), in multiple locations. The prevalence of pancreatic lesions increased with age; they were detected in 14% of subjects younger than 50 years old, 34% of subjects 50-59 years old, and 53% of subjects 60-69 years old (P < .0001). CT, MRI, and EUS detected a pancreatic abnormality in 11%, 33.3%, and 42.6% of the HRIs, respectively. Among these abnormalities, proven or suspected neoplasms were identified in 85 HRIs (82 intraductal papillary mucinous neoplasms and 3 pancreatic endocrine tumors). Three of 5 HRIs who underwent pancreatic resection had high-grade dysplasia in less than 3 cm intraductal papillary mucinous neoplasms and in multiple intraepithelial neoplasias.\nCONCLUSIONS: Screening of asymptomatic HRIs frequently detects small pancreatic cysts, including curable, noninvasive high-grade neoplasms. EUS and MRI detect pancreatic lesions better than CT.","DOI":"10.1053/j.gastro.2012.01.005","ISSN":"1528-0012","note":"PMID: 22245846\nPMCID: PMC3321068","journalAbbreviation":"Gastroenterology","language":"eng","author":[{"family":"Canto","given":"Marcia Irene"},{"family":"Hruban","given":"Ralph H."},{"family":"Fishman","given":"Elliot K."},{"family":"Kamel","given":"Ihab R."},{"family":"Schulick","given":"Richard"},{"family":"Zhang","given":"Zhe"},{"family":"Topazian","given":"Mark"},{"family":"Takahashi","given":"Naoki"},{"family":"Fletcher","given":"Joel"},{"family":"Petersen","given":"Gloria"},{"family":"Klein","given":"Alison P."},{"family":"Axilbund","given":"Jennifer"},{"family":"Griffin","given":"Constance"},{"family":"Syngal","given":"Sapna"},{"family":"Saltzman","given":"John R."},{"family":"Mortele","given":"Koenraad J."},{"family":"Lee","given":"Jeffrey"},{"family":"Tamm","given":"Eric"},{"family":"Vikram","given":"Raghunandan"},{"family":"Bhosale","given":"Priya"},{"family":"Margolis","given":"Daniel"},{"family":"Farrell","given":"James"},{"family":"Goggins","given":"Michael"},{"literal":"American Cancer of the Pancreas Screening (CAPS) Consortium"}],"issued":{"date-parts":[["2012",4]]}}}],"schema":""} [25] in 216 HRI, EUS, MRI and CT scan detected pancreatic abnormalities (cysts, solid lesions or chronic pancreatitis) in 42.6%, 33.3% and 11% of patients, respectively. This corresponded to a sensitivity of 93% for EUS for the detection of solid lesions smaller than 2 cm compared to 53% and 67% for CT scan and MRI, respectively ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"V3SN322d","properties":{"formattedCitation":"\\super [25]\\nosupersub{}","plainCitation":"[25]","noteIndex":0},"citationItems":[{"id":"BbVydael/sxr8Ecxk","uris":[""],"uri":[""],"itemData":{"id":58,"type":"article-journal","title":"Frequent detection of pancreatic lesions in asymptomatic high-risk individuals","container-title":"Gastroenterology","page":"796-804; quiz e14-15","volume":"142","issue":"4","source":"PubMed","abstract":"BACKGROUND & AIMS: The risk of pancreatic cancer is increased in patients with a strong family history of pancreatic cancer or a predisposing germline mutation. Screening can detect curable, noninvasive pancreatic neoplasms, but the optimal imaging approach is not known. We determined the baseline prevalence and characteristics of pancreatic abnormalities using 3 imaging tests to screen asymptomatic, high-risk individuals (HRIs).\nMETHODS: We screened 225 asymptomatic adult HRIs at 5 academic US medical centers once, using computed tomography (CT), magnetic resonance imaging (MRI), and endoscopic ultrasonography (EUS). We compared results in a blinded, independent fashion.\nRESULTS: Ninety-two of 216 HRIs (42%) were found to have at least 1 pancreatic mass (84 cystic, 3 solid) or a dilated pancreatic duct (n = 5) by any of the imaging modalities. Fifty-one of the 84 HRIs with a cyst (60.7%) had multiple lesions, typically small (mean, 0.55 cm; range, 2-39 mm), in multiple locations. The prevalence of pancreatic lesions increased with age; they were detected in 14% of subjects younger than 50 years old, 34% of subjects 50-59 years old, and 53% of subjects 60-69 years old (P < .0001). CT, MRI, and EUS detected a pancreatic abnormality in 11%, 33.3%, and 42.6% of the HRIs, respectively. Among these abnormalities, proven or suspected neoplasms were identified in 85 HRIs (82 intraductal papillary mucinous neoplasms and 3 pancreatic endocrine tumors). Three of 5 HRIs who underwent pancreatic resection had high-grade dysplasia in less than 3 cm intraductal papillary mucinous neoplasms and in multiple intraepithelial neoplasias.\nCONCLUSIONS: Screening of asymptomatic HRIs frequently detects small pancreatic cysts, including curable, noninvasive high-grade neoplasms. EUS and MRI detect pancreatic lesions better than CT.","DOI":"10.1053/j.gastro.2012.01.005","ISSN":"1528-0012","note":"PMID: 22245846\nPMCID: PMC3321068","journalAbbreviation":"Gastroenterology","language":"eng","author":[{"family":"Canto","given":"Marcia Irene"},{"family":"Hruban","given":"Ralph H."},{"family":"Fishman","given":"Elliot K."},{"family":"Kamel","given":"Ihab R."},{"family":"Schulick","given":"Richard"},{"family":"Zhang","given":"Zhe"},{"family":"Topazian","given":"Mark"},{"family":"Takahashi","given":"Naoki"},{"family":"Fletcher","given":"Joel"},{"family":"Petersen","given":"Gloria"},{"family":"Klein","given":"Alison P."},{"family":"Axilbund","given":"Jennifer"},{"family":"Griffin","given":"Constance"},{"family":"Syngal","given":"Sapna"},{"family":"Saltzman","given":"John R."},{"family":"Mortele","given":"Koenraad J."},{"family":"Lee","given":"Jeffrey"},{"family":"Tamm","given":"Eric"},{"family":"Vikram","given":"Raghunandan"},{"family":"Bhosale","given":"Priya"},{"family":"Margolis","given":"Daniel"},{"family":"Farrell","given":"James"},{"family":"Goggins","given":"Michael"},{"literal":"American Cancer of the Pancreas Screening (CAPS) Consortium"}],"issued":{"date-parts":[["2012",4]]}}}],"schema":""} [25]. Harinck et al ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"5stbumtQ","properties":{"formattedCitation":"\\super [27]\\nosupersub{}","plainCitation":"[27]","noteIndex":0},"citationItems":[{"id":"BbVydael/KLfm1MxF","uris":[""],"uri":[""],"itemData":{"id":38,"type":"article-journal","title":"A multicentre comparative prospective blinded analysis of EUS and MRI for screening of pancreatic cancer in high-risk individuals","container-title":"Gut","page":"1505-1513","volume":"65","issue":"9","source":"PubMed","abstract":"OBJECTIVE: Endoscopic ultrasonography (EUS) and MRI are promising tests to detect precursors and early-stage pancreatic ductal adenocarcinoma (PDAC) in high-risk individuals (HRIs). It is unclear which screening technique is to be preferred. We aimed to compare the efficacy of EUS and MRI in their ability to detect clinically relevant lesions in HRI.\nDESIGN: Multicentre prospective study. The results of 139 asymptomatic HRI (>10-fold increased risk) undergoing first-time screening by EUS and MRI are described. Clinically relevant lesions were defined as solid lesions, main duct intraductal papillary mucinous neoplasms and cysts ≥10?mm. Results were compared in a blinded, independent fashion.\nRESULTS: Two solid lesions (mean size 9?mm) and nine cysts ≥10?mm (mean size 17?mm) were detected in nine HRI (6%). Both solid lesions were detected by EUS only and proved to be a stage I PDAC and a multifocal pancreatic intraepithelial neoplasia 2. Of the nine cysts ≥10?mm, six were detected by both imaging techniques and three were detected by MRI only. The agreement between EUS and MRI for the detection of clinically relevant lesions was 55%. Of these clinically relevant lesions detected by both techniques, there was a good agreement for location and size.\nCONCLUSIONS: EUS and/or MRI detected clinically relevant pancreatic lesions in 6% of HRI. Both imaging techniques were complementary rather than interchangeable: contrary to EUS, MRI was found to be very sensitive for the detection of cystic lesions of any size; MRI, however, might have some important limitations with regard to the timely detection of solid lesions.","DOI":"10.1136/gutjnl-2014-308008","ISSN":"1468-3288","note":"PMID: 25986944","journalAbbreviation":"Gut","language":"eng","author":[{"family":"Harinck","given":"F."},{"family":"Konings","given":"I. C. a. W."},{"family":"Kluijt","given":"I."},{"family":"Poley","given":"J. W."},{"family":"Hooft","given":"J. E.","non-dropping-particle":"van"},{"family":"Dullemen","given":"H. M.","non-dropping-particle":"van"},{"family":"Nio","given":"C. Y."},{"family":"Krak","given":"N. C."},{"family":"Hermans","given":"J. J."},{"family":"Aalfs","given":"C. M."},{"family":"Wagner","given":"A."},{"family":"Sijmons","given":"R. H."},{"family":"Biermann","given":"K."},{"family":"Eijck","given":"C. H.","non-dropping-particle":"van"},{"family":"Gouma","given":"D. J."},{"family":"Dijkgraaf","given":"M. G. W."},{"family":"Fockens","given":"P."},{"family":"Bruno","given":"M. J."},{"literal":"Dutch research group on pancreatic cancer surveillance in high-risk individuals"}],"issued":{"date-parts":[["2016"]]}}}],"schema":""} [27] performed a prospective comparison of EUS and MRI for the detection of clinically relevant pancreatic lesions at initial screening of 139 HRI. In this study, EUS and/or MRI detected pancreatic lesions in 6% of HRI: 2 solid tumours < 10 mm were only detected by EUS (1 invasive PC and 1 PanIN with low-grade dysplasia), and 25% of cysts were only detected by MRI ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"azvt9Q2T","properties":{"formattedCitation":"\\super [27]\\nosupersub{}","plainCitation":"[27]","noteIndex":0},"citationItems":[{"id":"BbVydael/KLfm1MxF","uris":[""],"uri":[""],"itemData":{"id":38,"type":"article-journal","title":"A multicentre comparative prospective blinded analysis of EUS and MRI for screening of pancreatic cancer in high-risk individuals","container-title":"Gut","page":"1505-1513","volume":"65","issue":"9","source":"PubMed","abstract":"OBJECTIVE: Endoscopic ultrasonography (EUS) and MRI are promising tests to detect precursors and early-stage pancreatic ductal adenocarcinoma (PDAC) in high-risk individuals (HRIs). It is unclear which screening technique is to be preferred. We aimed to compare the efficacy of EUS and MRI in their ability to detect clinically relevant lesions in HRI.\nDESIGN: Multicentre prospective study. The results of 139 asymptomatic HRI (>10-fold increased risk) undergoing first-time screening by EUS and MRI are described. Clinically relevant lesions were defined as solid lesions, main duct intraductal papillary mucinous neoplasms and cysts ≥10?mm. Results were compared in a blinded, independent fashion.\nRESULTS: Two solid lesions (mean size 9?mm) and nine cysts ≥10?mm (mean size 17?mm) were detected in nine HRI (6%). Both solid lesions were detected by EUS only and proved to be a stage I PDAC and a multifocal pancreatic intraepithelial neoplasia 2. Of the nine cysts ≥10?mm, six were detected by both imaging techniques and three were detected by MRI only. The agreement between EUS and MRI for the detection of clinically relevant lesions was 55%. Of these clinically relevant lesions detected by both techniques, there was a good agreement for location and size.\nCONCLUSIONS: EUS and/or MRI detected clinically relevant pancreatic lesions in 6% of HRI. Both imaging techniques were complementary rather than interchangeable: contrary to EUS, MRI was found to be very sensitive for the detection of cystic lesions of any size; MRI, however, might have some important limitations with regard to the timely detection of solid lesions.","DOI":"10.1136/gutjnl-2014-308008","ISSN":"1468-3288","note":"PMID: 25986944","journalAbbreviation":"Gut","language":"eng","author":[{"family":"Harinck","given":"F."},{"family":"Konings","given":"I. C. a. W."},{"family":"Kluijt","given":"I."},{"family":"Poley","given":"J. W."},{"family":"Hooft","given":"J. E.","non-dropping-particle":"van"},{"family":"Dullemen","given":"H. M.","non-dropping-particle":"van"},{"family":"Nio","given":"C. Y."},{"family":"Krak","given":"N. C."},{"family":"Hermans","given":"J. J."},{"family":"Aalfs","given":"C. M."},{"family":"Wagner","given":"A."},{"family":"Sijmons","given":"R. H."},{"family":"Biermann","given":"K."},{"family":"Eijck","given":"C. H.","non-dropping-particle":"van"},{"family":"Gouma","given":"D. J."},{"family":"Dijkgraaf","given":"M. G. W."},{"family":"Fockens","given":"P."},{"family":"Bruno","given":"M. J."},{"literal":"Dutch research group on pancreatic cancer surveillance in high-risk individuals"}],"issued":{"date-parts":[["2016"]]}}}],"schema":""} [27]. Nevertheless, as all patients were not operated on, this study does not enable the evaluation of whether the lesions detected were all of pathological relevance. Table 2 reports the main characteristics of HRI screening techniques and imaging results in 16 published studies. Of note, MRI and CT scan protocols were not clearly described in most studies (e.g., matrix size, contrast enhancement, MRI sequences), and the results of EUS are well known to be operator-dependent as well as classical radiological procedures ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"hYkq1ZlW","properties":{"formattedCitation":"\\super [28,29]\\nosupersub{}","plainCitation":"[28,29]","noteIndex":0},"citationItems":[{"id":"BbVydael/VywnNPwr","uris":[""],"uri":[""],"itemData":{"id":140,"type":"article-journal","title":"Interobserver agreement for EUS findings in familial pancreatic-cancer kindreds","container-title":"Gastrointestinal Endoscopy","page":"62-67","volume":"66","issue":"1","source":"PubMed","abstract":"BACKGROUND: EUS is a promising modality for pancreatic-cancer screening in high-risk persons, including familial pancreatic-cancer (FPC) kindreds.\nOBJECTIVE: To assess interobserver agreement for interpretation of EUS in persons at high risk for pancreatic cancer.\nDESIGN: Seventeen expert endosonographers blinded to patients' clinical history rated a \"training set\" of pancreatic EUS video clips for the presence of a normal examination, masses, cysts, and features of chronic pancreatitis. Clips included high-risk persons and controls (normal and various pancreatic diseases). The endosonographers then participated in a workshop on EUS findings in high-risk persons and drafted a consensus statement. Three months later, they blindly rated a \"test set\" composed of the same video clips.\nMAIN OUTCOME MEASUREMENTS: Interobserver agreement at baseline (training set) and after a consensus process (test set).\nRESULTS: For the training set, interobserver agreement was good (kappa>or=0.4) for the presence of cysts and was fair to poor for all other rated EUS features and diagnosis of normal. There was no overall improvement in the test set. In both the training and test sets, agreement was worse for clips from FPC kindreds (kappa>or=0.4 for cysts and <0.4 for all other features) than for controls (kappa>or=0.4 for normal, cysts, masses, echogenic strands, and lobularity).\nLIMITATIONS: Video clips were not of identical image quality and duration as a clinical EUS examination.\nCONCLUSIONS: There was fair to poor interobserver agreement for the interpretation of pancreatic EUS video clips from members of FPC kindreds. Agreement was not improved by a consensus process.","DOI":"10.1016/j.gie.2006.09.018","ISSN":"0016-5107","note":"PMID: 17382940","journalAbbreviation":"Gastrointest. Endosc.","language":"eng","author":[{"family":"Topazian","given":"Mark"},{"family":"Enders","given":"Felicity"},{"family":"Kimmey","given":"Michael"},{"family":"Brand","given":"Randall"},{"family":"Chak","given":"Amitabh"},{"family":"Clain","given":"Jonathan"},{"family":"Cunningham","given":"John"},{"family":"Eloubeidi","given":"Mohamad"},{"family":"Gerdes","given":"Hans"},{"family":"Gress","given":"Frank"},{"family":"Jagannath","given":"Sanjay"},{"family":"Kantsevoy","given":"Sergey"},{"family":"LeBlanc","given":"Julia Kim"},{"family":"Levy","given":"Michael"},{"family":"Lightdale","given":"Charles"},{"family":"Romagnuolo","given":"Joseph"},{"family":"Saltzman","given":"John R."},{"family":"Savides","given":"Thomas"},{"family":"Wiersema","given":"Maurits"},{"family":"Woodward","given":"Timothy"},{"family":"Petersen","given":"Gloria"},{"family":"Canto","given":"Marcia"}],"issued":{"date-parts":[["2007",7]]}}},{"id":"BbVydael/8dACpTCE","uris":[""],"uri":[""],"itemData":{"id":116,"type":"article-journal","title":"Linear-array EUS improves detection of pancreatic lesions in high-risk individuals: a randomized tandem study","container-title":"Gastrointestinal Endoscopy","page":"812-818","volume":"82","issue":"5","source":"PubMed","abstract":"BACKGROUND: Studies comparing linear and radial EUS for the detection of pancreatic lesions in an asymptomatic population with increased risk for pancreatic cancer are lacking.\nOBJECTIVES: To compare pancreatic lesion detection rates between radial and linear EUS and to determine the incremental diagnostic yield of a second EUS examination.\nDESIGN: Randomized controlled tandem study.\nSETTING: Five academic centers in the United States.\nPATIENTS: Asymptomatic high-risk individuals (HRIs) for pancreatic cancer undergoing screening EUS.\nINTERVENTIONS: Linear and radial EUS performed in randomized order.\nMAIN OUTCOME MEASUREMENTS: Pancreatic lesion detection rate by type of EUS, miss rate of 1 EUS examination, and incremental diagnostic yield of a second EUS examination (second-pass effect).\nRESULTS: Two hundred seventy-eight HRIs were enrolled, mean age 56 years (43.2%), and 90% were familial pancreatic cancer relatives. Two hundred twenty-four HRIs underwent tandem radial and linear EUS. When we used per-patient analysis, the overall prevalence of any pancreatic lesion was 45%. Overall, 16 of 224 HRIs (7.1%) had lesions missed during the initial EUS that were detected by the second EUS examination. The per-patient lesion miss rate was significantly greater for radial followed by linear EUS (9.8%) than for linear followed by radial EUS (4.5%) (P?= .03). When we used per-lesion analysis, 73 of 109 lesions (67%) were detected by radial EUS and 99 of 120 lesions (82%) were detected by linear EUS (P?< .001) during the first examination. The overall miss rate for a pancreatic lesion after 1 EUS examination was 47 of 229 (25%). The miss rate was significantly lower for linear EUS compared with radial EUS (17.5% vs 33.0%, P?= .007).\nLIMITATIONS: Most detected pancreatic lesions were not confirmed by pathology.\nCONCLUSION: Linear EUS detects more pancreatic lesions than radial EUS. There was a \"second-pass effect\" with additional lesions detected with a second EUS examination. This effect was significantly greater when linear EUS was used after an initial radial EUS examination.","DOI":"10.1016/j.gie.2015.02.028","ISSN":"1097-6779","note":"PMID: 25930097\nPMCID: PMC4609234","title-short":"Linear-array EUS improves detection of pancreatic lesions in high-risk individuals","journalAbbreviation":"Gastrointest. Endosc.","language":"eng","author":[{"family":"Shin","given":"Eun Ji"},{"family":"Topazian","given":"Mark"},{"family":"Goggins","given":"Michael G."},{"family":"Syngal","given":"Sapna"},{"family":"Saltzman","given":"John R."},{"family":"Lee","given":"Jeffrey H."},{"family":"Farrell","given":"James J."},{"family":"Canto","given":"Marcia I."}],"issued":{"date-parts":[["2015",11]]}}}],"schema":""} [28,29]. Indeed, Topazian et al ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"3rSn0rjt","properties":{"formattedCitation":"\\super [28]\\nosupersub{}","plainCitation":"[28]","noteIndex":0},"citationItems":[{"id":"BbVydael/VywnNPwr","uris":[""],"uri":[""],"itemData":{"id":140,"type":"article-journal","title":"Interobserver agreement for EUS findings in familial pancreatic-cancer kindreds","container-title":"Gastrointestinal Endoscopy","page":"62-67","volume":"66","issue":"1","source":"PubMed","abstract":"BACKGROUND: EUS is a promising modality for pancreatic-cancer screening in high-risk persons, including familial pancreatic-cancer (FPC) kindreds.\nOBJECTIVE: To assess interobserver agreement for interpretation of EUS in persons at high risk for pancreatic cancer.\nDESIGN: Seventeen expert endosonographers blinded to patients' clinical history rated a \"training set\" of pancreatic EUS video clips for the presence of a normal examination, masses, cysts, and features of chronic pancreatitis. Clips included high-risk persons and controls (normal and various pancreatic diseases). The endosonographers then participated in a workshop on EUS findings in high-risk persons and drafted a consensus statement. Three months later, they blindly rated a \"test set\" composed of the same video clips.\nMAIN OUTCOME MEASUREMENTS: Interobserver agreement at baseline (training set) and after a consensus process (test set).\nRESULTS: For the training set, interobserver agreement was good (kappa>or=0.4) for the presence of cysts and was fair to poor for all other rated EUS features and diagnosis of normal. There was no overall improvement in the test set. In both the training and test sets, agreement was worse for clips from FPC kindreds (kappa>or=0.4 for cysts and <0.4 for all other features) than for controls (kappa>or=0.4 for normal, cysts, masses, echogenic strands, and lobularity).\nLIMITATIONS: Video clips were not of identical image quality and duration as a clinical EUS examination.\nCONCLUSIONS: There was fair to poor interobserver agreement for the interpretation of pancreatic EUS video clips from members of FPC kindreds. Agreement was not improved by a consensus process.","DOI":"10.1016/j.gie.2006.09.018","ISSN":"0016-5107","note":"PMID: 17382940","journalAbbreviation":"Gastrointest. Endosc.","language":"eng","author":[{"family":"Topazian","given":"Mark"},{"family":"Enders","given":"Felicity"},{"family":"Kimmey","given":"Michael"},{"family":"Brand","given":"Randall"},{"family":"Chak","given":"Amitabh"},{"family":"Clain","given":"Jonathan"},{"family":"Cunningham","given":"John"},{"family":"Eloubeidi","given":"Mohamad"},{"family":"Gerdes","given":"Hans"},{"family":"Gress","given":"Frank"},{"family":"Jagannath","given":"Sanjay"},{"family":"Kantsevoy","given":"Sergey"},{"family":"LeBlanc","given":"Julia Kim"},{"family":"Levy","given":"Michael"},{"family":"Lightdale","given":"Charles"},{"family":"Romagnuolo","given":"Joseph"},{"family":"Saltzman","given":"John R."},{"family":"Savides","given":"Thomas"},{"family":"Wiersema","given":"Maurits"},{"family":"Woodward","given":"Timothy"},{"family":"Petersen","given":"Gloria"},{"family":"Canto","given":"Marcia"}],"issued":{"date-parts":[["2007",7]]}}}],"schema":""} [28] report a low interobserver agreement for the interpretation of pancreatic EUS in HRI (Kappa < 0.4 except for cysts). This is probably due to the lack of specific training for EUS, the lack of a standardized collection chart and a specific learning curve. Although all of the abovementioned studies included operated patients, the methods of detection of the pancreatic abnormalities that determined the surgical procedure were not described in detail. Thus, while the precise value of EUS compared to the other modalities is probably high (it may find more (pre)malignant lesions), this is difficult to determine in the absence of a large study correlating anatomopathological specimens to EUS findings.There are no approved biomarkers for the screening of PC in HRI. Only one study has reported the results of serum CA19-9 measurement for pancreatic screening in these patients. Twenty-seven out of 546 included patients (4.9%) had elevated CA19-9, and 5 (18.5%) of these had pancreatic lesions (1 PC, 2 IPMN, 1 PanIN, 1 neuroendocrine tumour). Nevertheless, the number of pancreatic lesions in the group with normal CA 19-9 levels was not reported ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"oRGR22aT","properties":{"formattedCitation":"\\super [16]\\nosupersub{}","plainCitation":"[16]","noteIndex":0},"citationItems":[{"id":"BbVydael/9sdQOJDj","uris":[""],"uri":[""],"itemData":{"id":88,"type":"article-journal","title":"Screening for pancreatic cancer in a high-risk population with serum CA 19-9 and targeted EUS: a feasibility study","container-title":"Gastrointestinal Endoscopy","page":"87-95","volume":"74","issue":"1","source":"PubMed","abstract":"BACKGROUND: Earlier detection of pancreatic adenocarcinoma is needed.\nOBJECTIVE: To determine whether early pancreatic neoplasia can be detected in a high-risk population by using CA 19-9 followed by targeted EUS.\nDESIGN: Prospective cohort study.\nSETTING: Two academic medical centers.\nPATIENTS: Eligible patients met age criteria and had at least 1 first-degree relative with pancreatic adenocarcinoma.\nINTERVENTIONS: A serum CA 19-9 was performed on all patients. EUS was performed if the CA 19-9 level was elevated. FNA of identified lesions was performed. Patients with pancreatic cancer detected by using this screening protocol were compared with patients presenting off-protocol for staging data. Medicare reimbursement rates were used to derive cost data.\nMAIN OUTCOME MEASUREMENTS: Detection of early pancreatic neoplasia.\nRESULTS: A total of 546 patients were enrolled. CA 19-9 was elevated in 27 patients (4.9%, 95% CI, 3.2%-7.1%). Neoplastic or malignant findings were detected in 5 patients (0.9%, 95% CI, 0.3%-2.1%), and pancreatic adenocarcinoma in 1 patient (0.2%, 95% CI, 0.005%-1.02%). The patient with pancreatic cancer detected as part of this protocol was 1 of 2 patients presenting to the University of Vermont with stage 1 cancer. The cost to detect 1 pancreatic neoplasia was $8431. The cost to detect 1 pancreatic adenocarcinoma was $41,133.\nLIMITATIONS: The sample size is adequate only to demonstrate the feasibility of this approach.\nCONCLUSIONS: Potentially curative pancreatic adenocarcinoma can be identified with this screening protocol. Stage 1 pancreatic cancer is more likely to be detected by using this screening protocol than by using standard means of detection.","DOI":"10.1016/j.gie.2011.03.1235","ISSN":"1097-6779","note":"PMID: 21704809","title-short":"Screening for pancreatic cancer in a high-risk population with serum CA 19-9 and targeted EUS","journalAbbreviation":"Gastrointest. Endosc.","language":"eng","author":[{"family":"Zubarik","given":"Richard"},{"family":"Gordon","given":"Stuart R."},{"family":"Lidofsky","given":"Steven D."},{"family":"Anderson","given":"Scott R."},{"family":"Pipas","given":"J. Marc"},{"family":"Badger","given":"Gary"},{"family":"Ganguly","given":"Eric"},{"family":"Vecchio","given":"James"}],"issued":{"date-parts":[["2011",7]]}}}],"schema":""} [16]. CA19-9 is not recommended because of its low sensitivity and specificity ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"ahvELShr","properties":{"formattedCitation":"\\super [11,17\\uc0\\u8211{}19,30]\\nosupersub{}","plainCitation":"[11,17–19,30]","noteIndex":0},"citationItems":[{"id":"BbVydael/iMJ7y1A2","uris":[""],"uri":[""],"itemData":{"id":33,"type":"article-journal","title":"Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma: a patient-level meta-analysis and proposition of the Beaujon score","container-title":"United European Gastroenterology Journal","page":"205064061882491","source":"Crossref","DOI":"10.1177/2050640618824910","ISSN":"2050-6406, 2050-6414","title-short":"Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma","language":"en","author":[{"family":"Mestier","given":"Louis","non-dropping-particle":"de"},{"family":"Muller","given":"Marie"},{"family":"Cros","given":"Jér?me"},{"family":"Vullierme","given":"Marie-Pierre"},{"family":"Vernerey","given":"Dewi"},{"family":"Maire","given":"Frédérique"},{"family":"Dokmak","given":"Safi"},{"family":"Rebours","given":"Vinciane"},{"family":"Sauvanet","given":"Alain"},{"family":"Lévy","given":"Philippe"},{"family":"Hammel","given":"Pascal"}],"issued":{"date-parts":[["2019",1,12]]}}},{"id":"BbVydael/Cz27nE6J","uris":[""],"uri":[""],"itemData":{"id":17,"type":"article-journal","title":"Evaluating Susceptibility to Pancreatic Cancer: ASCO Clinical Practice Provisional Clinical Opinion Summary","container-title":"Journal of Oncology Practice","page":"108-111","volume":"15","issue":"2","source":"PubMed","DOI":"10.1200/JOP.18.00629","ISSN":"1935-469X","note":"PMID: 30589608","title-short":"Evaluating Susceptibility to Pancreatic Cancer","journalAbbreviation":"J Oncol Pract","language":"eng","author":[{"family":"Stoffel","given":"Elena M."},{"family":"McKernin","given":"Shannon E."},{"family":"Khorana","given":"Alok A."}],"issued":{"date-parts":[["2019",2]]}}},{"id":"BbVydael/C3zHNTfr","uris":[""],"uri":[""],"itemData":{"id":95,"type":"article-journal","title":"Results of surveillance in individuals at high-risk of pancreatic cancer: A systematic review and meta-analysis","container-title":"United European Gastroenterology Journal","page":"489-499","volume":"6","issue":"4","source":"PubMed","abstract":"Background: Data on surveillance for pancreatic ductal adenocarcinoma (PDAC) in high-risk individuals (HRIs) with \"familial pancreatic cancer\" (FPC) and specific syndromes are limited and heterogeneous.\nObjective: We conducted a systematic review and meta-analysis of PDAC surveillance studies in HRIs.\nMethods: Prevalence of solid/cystic pancreatic lesions and of lesions considered a successful target of surveillance (proven resectable PDAC and high-grade precursors) was pooled across studies. The rate of lesions diagnosed by endoscopic ultrasonography (EUS)/magnetic resonance imaging (MRI) and across different HRI groups was calculated.\nResults: Sixteen studies incorporating 1588 HRIs were included. The pooled prevalence of pancreatic solid and cystic lesions was 5.8% and 20.2%, respectively. The pooled prevalence of patients with lesions considered a successful target of surveillance was 3.3%, being similar to EUS or MRI and varying across subgroups, being 3% in FPC, 4% in hereditary pancreatitis, 5% in familial melanoma, 6.3% in hereditary breast/ovarian cancer, and 12.2% in Peutz-Jeghers syndrome. The pooled estimated rate of lesions considered a successful target of surveillance during follow-up was 5/1000 person-years.\nConclusion: Surveillance programs identify successful target lesions in 3.3% of HRIs with a similar yield of EUS and MRI and an annual risk of 0.5%. A higher rate of target lesions was reported in HRIs with specific DNA mutations.","DOI":"10.1177/2050640617752182","ISSN":"2050-6406","note":"PMID: 29881603\nPMCID: PMC5987280","title-short":"Results of surveillance in individuals at high-risk of pancreatic cancer","journalAbbreviation":"United European Gastroenterol J","language":"eng","author":[{"family":"Signoretti","given":"Marianna"},{"family":"Bruno","given":"Marco J."},{"family":"Zerboni","given":"Giulia"},{"family":"Poley","given":"Jan-Werner"},{"family":"Delle Fave","given":"Gianfranco"},{"family":"Capurso","given":"Gabriele"}],"issued":{"date-parts":[["2018",5]]}}},{"id":"BbVydael/39vT8LTF","uris":[""],"uri":[""],"itemData":{"id":98,"type":"article-journal","title":"Diagnostic Yield From Screening Asymptomatic Individuals at?High Risk for Pancreatic Cancer: A Meta-analysis of Cohort?Studies","container-title":"Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association","page":"41-53","volume":"17","issue":"1","source":"PubMed","abstract":"BACKGROUND & AIMS: There have been few studies of abdominal imaging screening of individuals at high risk for pancreatic cancer (based on family history or genetic variants). We performed a meta-analysis of prospective cohort studies to determine the diagnostic yield and outcomes of abdominal imaging screening for asymptomatic individuals at high risk.\nMETHODS: Through a systematic review of multiple electronic databases and conference proceedings through July 2017, we identified prospective cohort studies (>20 patients) of asymptomatic adults determined to be at high-risk of pancreatic cancer (lifetime risk >5%, including specific genetic-associated conditions) who were screened by endoscopic ultrasound (EUS) and/or magnetic resonance imaging (MRI) to detect pancreatic lesions. Our primary outcome was identification of high-risk pancreatic lesions (high-grade pancreatic intraepithelial neoplasia, high-grade dysplasia, or adenocarcinoma) at initial screening, and overall incidence during follow up. Summary estimates were reported as incidence rates per 100 patient-years.\nRESULTS: We identified 19 studies comprising 7085 individuals at high risk for pancreatic cancer; of these, 1660 patients were evaluated by EUS and/or MRI. Fifty-nine high-risk lesions were identified (43 adenocarcinomas: 28 during the initial exam and 15 during follow-up surveillance) and 257 patients underwent pancreatic surgery. Based on our meta-analysis, the overall diagnostic yield screening for high-risk pancreatic lesions was 0.74 (95% CI, 0.33-1.14), with moderate heterogeneity among studies. The number needed to screen to identify 1 patient with?a high-risk lesion was 135 (95% CI, 88-303). The diagnostic yield was similar for patients with different genetic features that increased risk, and whether patients were screened by EUS or MRI.\nCONCLUSIONS: Based on meta-analysis, 135 patients at high-risk for pancreatic cancer must be screened to identify 1 patient with a high-risk pancreatic lesion. Further studies are needed to determine whether screening reduces mortality and is cost effectiveness for individuals at high-risk of pancreatic cancer.","DOI":"10.1016/j.cgh.2018.04.065","ISSN":"1542-7714","note":"PMID: 29775792","title-short":"Diagnostic Yield From Screening Asymptomatic Individuals at?High Risk for Pancreatic Cancer","journalAbbreviation":"Clin. Gastroenterol. Hepatol.","language":"eng","author":[{"family":"Corral","given":"Juan E."},{"family":"Mareth","given":"Karl F."},{"family":"Riegert-Johnson","given":"Douglas L."},{"family":"Das","given":"Ananya"},{"family":"Wallace","given":"Michael B."}],"issued":{"date-parts":[["2019",1]]}}},{"id":"BbVydael/HMFnecr3","uris":[""],"uri":[""],"itemData":{"id":31,"type":"article-journal","title":"Risk of Neoplastic Progression in Individuals at High Risk for Pancreatic Cancer Undergoing Long-term Surveillance","container-title":"Gastroenterology","page":"740-751.e2","volume":"155","issue":"3","source":"PubMed","abstract":"BACKGROUND & AIMS: Screening of individuals who have a high risk of pancreatic ductal adenocarcinoma (PDAC), because of genetic factors, frequently leads to identification of pancreatic lesions. We investigated the incidence of PDAC and risk factors for neoplastic progression in individuals at high risk for PDAC enrolled in a long-term screening study.\nMETHODS: We analyzed data from 354 individuals at high risk for PDAC (based on genetic factors of family history), enrolled in Cancer of the Pancreas Screening cohort studies at tertiary care academic centers from 1998 through 2014 (median follow-up time, 5.6 years). All subjects were evaluated at study entry (baseline) by endoscopic ultrasonography and underwent surveillance with endoscopic ultrasonography, magnetic resonance imaging, and/or computed tomography. The primary endpoint was the cumulative incidence of PDAC, pancreatic intraepithelial neoplasia grade 3, or intraductal papillary mucinous neoplasm with high-grade dysplasia (HGD) after baseline. We performed multivariate Cox regression and Kaplan-Meier analyses.\nRESULTS: During the follow-up period, pancreatic lesions with worrisome features (solid mass, multiple cysts, cyst size > 3 cm, thickened/enhancing walls, mural nodule, dilated main pancreatic duct > 5 mm, or abrupt change in duct caliber) or rapid cyst growth (>4 mm/year) were detected in 68 patients (19%). Overall, 24 of 354 patients (7%) had neoplastic progression (14 PDACs and 10 HGDs) over a 16-year period; the rate of progression was 1.6%/year, and 93% had detectable lesions with worrisome features before diagnosis of the PDAC or HGD. Nine of the 10 PDACs detected during routine surveillance were resectable; a significantly higher proportion of patients with resectable PDACs survived 3?years (85%) compared with the 4 subjects with symptomatic, unresectable PDACs (25%), which developed outside surveillance (log rank P < .0001). Neoplastic progression occurred at a median age of 67 years; the median time from baseline screening until PDAC diagnosis was 4.8 years (interquartile range, 1.6-6.9 years).\nCONCLUSIONS: In a long-term (16-year) follow-up study of individuals at high-risk for PDAC, we found most PDACs detected during surveillance (9/10) to be resectable, and 85% of these patients survived for 3 years. We?identified radiologic features associated with neoplastic progression.","DOI":"10.1053/j.gastro.2018.05.035","ISSN":"1528-0012","note":"PMID: 29803839\nPMCID: PMC6120797","journalAbbreviation":"Gastroenterology","language":"eng","author":[{"family":"Canto","given":"Marcia Irene"},{"family":"Almario","given":"Jose Alejandro"},{"family":"Schulick","given":"Richard D."},{"family":"Yeo","given":"Charles J."},{"family":"Klein","given":"Alison"},{"family":"Blackford","given":"Amanda"},{"family":"Shin","given":"Eun Ji"},{"family":"Sanyal","given":"Abanti"},{"family":"Yenokyan","given":"Gayane"},{"family":"Lennon","given":"Anne Marie"},{"family":"Kamel","given":"Ihab R."},{"family":"Fishman","given":"Elliot K."},{"family":"Wolfgang","given":"Christopher"},{"family":"Weiss","given":"Matthew"},{"family":"Hruban","given":"Ralph H."},{"family":"Goggins","given":"Michael"}],"issued":{"date-parts":[["2018"]]}}}],"schema":""} [11,17–19,30].The recent CAPS (International?Cancer?of the?Pancreas?Screening?) consensus has suggested that annual MRI [including magnetic resonance cholangio-pancreatography (MRCP)] and EUS are the best imaging modalities for the detection of significant PC precursor lesions ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"JPG2Q3Xx","properties":{"formattedCitation":"\\super [6]\\nosupersub{}","plainCitation":"[6]","noteIndex":0},"citationItems":[{"id":"BbVydael/ATi5U74k","uris":[""],"uri":[""],"itemData":{"id":19,"type":"article-journal","title":"International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer","container-title":"Gut","page":"339-347","volume":"62","issue":"3","source":"PubMed","abstract":"BACKGROUND: Screening individuals at increased risk for pancreatic cancer (PC) detects early, potentially curable, pancreatic neoplasia.\nOBJECTIVE: To develop consortium statements on screening, surveillance and management of high-risk individuals with an inherited predisposition to PC.\nMETHODS: A 49-expert multidisciplinary international consortium met to discuss pancreatic screening and vote on statements. Consensus was considered reached if ≥ 75% agreed or disagreed.\nRESULTS: There was excellent agreement that, to be successful, a screening programme should detect and treat T1N0M0 margin-negative PC and high-grade dysplastic precursor lesions (pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasm). It was agreed that the following were candidates for screening: first-degree relatives (FDRs) of patients with PC from a familial PC kindred with at least two affected FDRs; patients with Peutz-Jeghers syndrome; and p16, BRCA2 and hereditary non-polyposis colorectal cancer (HNPCC) mutation carriers with ≥ 1 affected FDR. Consensus was not reached for the age to initiate screening or stop surveillance. It was agreed that initial screening should include endoscopic ultrasonography (EUS) and/or MRI/magnetic resonance cholangiopancreatography not CT or endoscopic retrograde cholangiopancreatography. There was no consensus on the need for EUS fine-needle aspiration to evaluate cysts. There was disagreement on optimal screening modalities and intervals for follow-up imaging. When surgery is recommended it should be performed at a high-volume centre. There was great disagreement as to which screening abnormalities were of sufficient concern to for surgery to be recommended.\nCONCLUSIONS: Screening is recommended for high-risk individuals, but more evidence is needed, particularly for how to manage patients with detected lesions. Screening and subsequent management should take place at high-volume centres with multidisciplinary teams, preferably within research protocols.","DOI":"10.1136/gutjnl-2012-303108","ISSN":"1468-3288","note":"PMID: 23135763\nPMCID: PMC3585492","journalAbbreviation":"Gut","language":"eng","author":[{"family":"Canto","given":"Marcia Irene"},{"family":"Harinck","given":"Femme"},{"family":"Hruban","given":"Ralph H."},{"family":"Offerhaus","given":"George Johan"},{"family":"Poley","given":"Jan-Werner"},{"family":"Kamel","given":"Ihab"},{"family":"Nio","given":"Yung"},{"family":"Schulick","given":"Richard S."},{"family":"Bassi","given":"Claudio"},{"family":"Kluijt","given":"Irma"},{"family":"Levy","given":"Michael J."},{"family":"Chak","given":"Amitabh"},{"family":"Fockens","given":"Paul"},{"family":"Goggins","given":"Michael"},{"family":"Bruno","given":"Marco"},{"literal":"International Cancer of Pancreas Screening (CAPS) Consortium"}],"issued":{"date-parts":[["2013",3]]}}}],"schema":""} [6]. In summary, and as recommended by the recent statement by the American Society of Clinical Oncology, pancreatic screening and follow-up in HRI should be based on MRI and EUS as complementary tests for the detection of pancreatic lesions ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"Fh0p1OTX","properties":{"formattedCitation":"\\super [17]\\nosupersub{}","plainCitation":"[17]","noteIndex":0},"citationItems":[{"id":"BbVydael/Cz27nE6J","uris":[""],"uri":[""],"itemData":{"id":17,"type":"article-journal","title":"Evaluating Susceptibility to Pancreatic Cancer: ASCO Clinical Practice Provisional Clinical Opinion Summary","container-title":"Journal of Oncology Practice","page":"108-111","volume":"15","issue":"2","source":"PubMed","DOI":"10.1200/JOP.18.00629","ISSN":"1935-469X","note":"PMID: 30589608","title-short":"Evaluating Susceptibility to Pancreatic Cancer","journalAbbreviation":"J Oncol Pract","language":"eng","author":[{"family":"Stoffel","given":"Elena M."},{"family":"McKernin","given":"Shannon E."},{"family":"Khorana","given":"Alok A."}],"issued":{"date-parts":[["2019",2]]}}}],"schema":""} [17]. When and how often should screening be performed?While pancreatic screening usually begins when HRI are 40 years old, or 10 years before the youngest index case ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"OU0HJW6l","properties":{"formattedCitation":"\\super [23]\\nosupersub{}","plainCitation":"[23]","noteIndex":0},"citationItems":[{"id":"BbVydael/NFPiCpG1","uris":[""],"uri":[""],"itemData":{"id":46,"type":"article-journal","title":"Screening for early pancreatic neoplasia in high-risk individuals: a prospective controlled study","container-title":"Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association","page":"766-781; quiz 665","volume":"4","issue":"6","source":"PubMed","abstract":"BACKGROUND & AIMS: Individuals with a strong family history of pancreatic cancer and persons with Peutz-Jeghers syndrome (PJS) have an increased risk for pancreatic cancer. This study screened for early pancreatic neoplasia and compared the pancreatic abnormalities in high-risk individuals and control subjects.\nMETHODS: High-risk individuals with PJS or a strong family history of pancreatic cancer were prospectively evaluated with baseline and 12-month computed tomography (CT) scan and endoscopic ultrasonography (EUS). If EUS was abnormal, EUS-fine-needle aspiration and endoscopic retrograde cholangiopancreatography (ERCP) were performed. Surgery was offered to patients with potentially neoplastic lesions. Radiologic findings and pathologic diagnoses were compared. Patients undergoing EUS and/or ERCP for benign non-pancreatic indications were concurrently enrolled as control subjects.\nRESULTS: Seventy-eight high-risk patients (72 from familial pancreatic cancer kindreds, 6 PJS) and 149 control patients were studied. To date, 8 patients with pancreatic neoplasia have been confirmed by surgery or fine-needle aspiration (10% yield of screening); 6 patients had 8 benign intraductal papillary mucinous neoplasms (IPMNs), 1 had an IPMN that progressed to invasive ductal adenocarcinoma, and 1 had pancreatic intraepithelial neoplasia. EUS and CT also diagnosed 3 patients with 5 extrapancreatic neoplasms. At EUS and ERCP abnormalities suggestive of chronic pancreatitis were more common in high-risk patients than in control subjects.\nCONCLUSIONS: Screening EUS and CT diagnosed significant asymptomatic pancreatic and extrapancreatic neoplasms in high-risk individuals. IPMN should be considered a part of the phenotype of familial pancreatic cancer. Abnormalities suggestive of chronic pancreatitis are identified more commonly at EUS and ERCP in high-risk individuals.","DOI":"10.1016/j.cgh.2006.02.005","ISSN":"1542-3565","note":"PMID: 16682259","title-short":"Screening for early pancreatic neoplasia in high-risk individuals","journalAbbreviation":"Clin. Gastroenterol. Hepatol.","language":"eng","author":[{"family":"Canto","given":"Marcia Irene"},{"family":"Goggins","given":"Michael"},{"family":"Hruban","given":"Ralph H."},{"family":"Petersen","given":"Gloria M."},{"family":"Giardiello","given":"Francis M."},{"family":"Yeo","given":"Charles"},{"family":"Fishman","given":"Elliott K."},{"family":"Brune","given":"Kieran"},{"family":"Axilbund","given":"Jennifer"},{"family":"Griffin","given":"Constance"},{"family":"Ali","given":"Syed"},{"family":"Richman","given":"Jeffrey"},{"family":"Jagannath","given":"Sanjay"},{"family":"Kantsevoy","given":"Sergey V."},{"family":"Kalloo","given":"Anthony N."}],"issued":{"date-parts":[["2006",6]]}}}],"schema":""} [23], this has recently been challenged because pancreatic screening rarely reveals relevant lesions before the age of 50 ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"FTYdYNyH","properties":{"formattedCitation":"\\super [4]\\nosupersub{}","plainCitation":"[4]","noteIndex":0},"citationItems":[{"id":"BbVydael/zZTZnNXC","uris":[""],"uri":[""],"itemData":{"id":36,"type":"article-journal","title":"Refinement of screening for familial pancreatic cancer","container-title":"Gut","page":"1314-1321","volume":"65","issue":"8","source":"PubMed","abstract":"OBJECTIVE: Surveillance programmes are recommended for individuals at risk (IAR) of familial pancreatic cancer (FPC) to detect early pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC). However, the age to begin screening and the optimal screening protocol remain to be determined.\nMETHODS: IAR from non-CDKN2A FPC families underwent annual screening by MRI with endoscopic ultrasonography (EUS) in board-approved prospective screening programmes at three tertiary referral centres. The diagnostic yield according to age and different screening protocols was analysed.\nRESULTS: 253 IAR with a median age of 48 (25-81)?years underwent screening with a median of 3 (1-11) screening visits during a median follow-up of 28 (1-152)?months. 134 (53%) IAR revealed pancreatic lesions on imaging, mostly cystic (94%), on baseline or follow-up screening. Lesions were significantly more often identified in IAR above the age of 45?years (p<0.0001). In 21 IAR who underwent surgery, no significant lesions (PDAC, pancreatic intraepithelial neoplasia (PanIN) 3 lesions, high-grade intraductal papillary mucinous neoplasia (IPMN)) were detected before the age of 50?years. Potentially relevant lesions (multifocal PanIN2 lesions, low/moderate-grade branch-duct IPMNs) occurred also significantly more often after the age of 50?years (13 vs 2, p<0.0004). The diagnostic yield of potentially relevant lesions was not different between screening protocols using annual MRI with EUS (n=98) or annual MRI with EUS every 3rd year (n=198) and between IAR screened at intervals of 12?months (n=180) or IAR that decided to be screened at ≥24?months intervals (n=30).\nCONCLUSIONS: It appears safe to start screening for PDAC in IAR of non-CDKN2a FPC families at the age of 50?years. MRI-based screening supplemented by EUS at baseline and every 3rd year or when changes in MRI occur appears to be efficient.","DOI":"10.1136/gutjnl-2015-311098","ISSN":"1468-3288","note":"PMID: 27222532","journalAbbreviation":"Gut","language":"eng","author":[{"family":"Bartsch","given":"D. K."},{"family":"Slater","given":"E. P."},{"family":"Carrato","given":"A."},{"family":"Ibrahim","given":"I. S."},{"family":"Guillen-Ponce","given":"C."},{"family":"Vasen","given":"H. F. A."},{"family":"Matth?i","given":"E."},{"family":"Earl","given":"J."},{"family":"Jendryschek","given":"F. S."},{"family":"Figiel","given":"J."},{"family":"Steinkamp","given":"M."},{"family":"Ramaswamy","given":"A."},{"family":"Vázquez-Sequeiros","given":"E."},{"family":"Mu?oz-Beltran","given":"M."},{"family":"Montans","given":"J."},{"family":"Mocci","given":"E."},{"family":"Bonsing","given":"B. A."},{"family":"Wasser","given":"M."},{"family":"Kl?ppel","given":"G."},{"family":"Langer","given":"P."},{"family":"Fendrich","given":"V."},{"family":"Gress","given":"T. M."}],"issued":{"date-parts":[["2016"]]}}}],"schema":""} [4]. We also recently reported that the risk of HGD or invasive cancer was 3 times higher in HRI > 50 years old operated on for pancreatic lesions than in HRI < 50 years old ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"xddSRrUV","properties":{"formattedCitation":"\\super [11]\\nosupersub{}","plainCitation":"[11]","noteIndex":0},"citationItems":[{"id":"BbVydael/iMJ7y1A2","uris":[""],"uri":[""],"itemData":{"id":33,"type":"article-journal","title":"Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma: a patient-level meta-analysis and proposition of the Beaujon score","container-title":"United European Gastroenterology Journal","page":"205064061882491","source":"Crossref","DOI":"10.1177/2050640618824910","ISSN":"2050-6406, 2050-6414","title-short":"Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma","language":"en","author":[{"family":"Mestier","given":"Louis","non-dropping-particle":"de"},{"family":"Muller","given":"Marie"},{"family":"Cros","given":"Jér?me"},{"family":"Vullierme","given":"Marie-Pierre"},{"family":"Vernerey","given":"Dewi"},{"family":"Maire","given":"Frédérique"},{"family":"Dokmak","given":"Safi"},{"family":"Rebours","given":"Vinciane"},{"family":"Sauvanet","given":"Alain"},{"family":"Lévy","given":"Philippe"},{"family":"Hammel","given":"Pascal"}],"issued":{"date-parts":[["2019",1,12]]}}}],"schema":""} [11].It is important to note that the majority of relevant pancreatic lesions (> 50% of cysts and solid tumours) are identified at the first screening rather than during follow-up ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"6Apjl2XC","properties":{"formattedCitation":"\\super [23,31,32]\\nosupersub{}","plainCitation":"[23,31,32]","noteIndex":0},"citationItems":[{"id":"BbVydael/NFPiCpG1","uris":[""],"uri":[""],"itemData":{"id":46,"type":"article-journal","title":"Screening for early pancreatic neoplasia in high-risk individuals: a prospective controlled study","container-title":"Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association","page":"766-781; quiz 665","volume":"4","issue":"6","source":"PubMed","abstract":"BACKGROUND & AIMS: Individuals with a strong family history of pancreatic cancer and persons with Peutz-Jeghers syndrome (PJS) have an increased risk for pancreatic cancer. This study screened for early pancreatic neoplasia and compared the pancreatic abnormalities in high-risk individuals and control subjects.\nMETHODS: High-risk individuals with PJS or a strong family history of pancreatic cancer were prospectively evaluated with baseline and 12-month computed tomography (CT) scan and endoscopic ultrasonography (EUS). If EUS was abnormal, EUS-fine-needle aspiration and endoscopic retrograde cholangiopancreatography (ERCP) were performed. Surgery was offered to patients with potentially neoplastic lesions. Radiologic findings and pathologic diagnoses were compared. Patients undergoing EUS and/or ERCP for benign non-pancreatic indications were concurrently enrolled as control subjects.\nRESULTS: Seventy-eight high-risk patients (72 from familial pancreatic cancer kindreds, 6 PJS) and 149 control patients were studied. To date, 8 patients with pancreatic neoplasia have been confirmed by surgery or fine-needle aspiration (10% yield of screening); 6 patients had 8 benign intraductal papillary mucinous neoplasms (IPMNs), 1 had an IPMN that progressed to invasive ductal adenocarcinoma, and 1 had pancreatic intraepithelial neoplasia. EUS and CT also diagnosed 3 patients with 5 extrapancreatic neoplasms. At EUS and ERCP abnormalities suggestive of chronic pancreatitis were more common in high-risk patients than in control subjects.\nCONCLUSIONS: Screening EUS and CT diagnosed significant asymptomatic pancreatic and extrapancreatic neoplasms in high-risk individuals. IPMN should be considered a part of the phenotype of familial pancreatic cancer. Abnormalities suggestive of chronic pancreatitis are identified more commonly at EUS and ERCP in high-risk individuals.","DOI":"10.1016/j.cgh.2006.02.005","ISSN":"1542-3565","note":"PMID: 16682259","title-short":"Screening for early pancreatic neoplasia in high-risk individuals","journalAbbreviation":"Clin. Gastroenterol. Hepatol.","language":"eng","author":[{"family":"Canto","given":"Marcia Irene"},{"family":"Goggins","given":"Michael"},{"family":"Hruban","given":"Ralph H."},{"family":"Petersen","given":"Gloria M."},{"family":"Giardiello","given":"Francis M."},{"family":"Yeo","given":"Charles"},{"family":"Fishman","given":"Elliott K."},{"family":"Brune","given":"Kieran"},{"family":"Axilbund","given":"Jennifer"},{"family":"Griffin","given":"Constance"},{"family":"Ali","given":"Syed"},{"family":"Richman","given":"Jeffrey"},{"family":"Jagannath","given":"Sanjay"},{"family":"Kantsevoy","given":"Sergey V."},{"family":"Kalloo","given":"Anthony N."}],"issued":{"date-parts":[["2006",6]]}}},{"id":"BbVydael/Sm6GTEmo","uris":[""],"uri":[""],"itemData":{"id":70,"type":"article-journal","title":"Benefit of Surveillance for Pancreatic Cancer in High-Risk Individuals: Outcome of Long-Term Prospective Follow-Up Studies From Three European Expert Centers","container-title":"Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology","page":"2010-2019","volume":"34","issue":"17","source":"PubMed","abstract":"PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis. Hereditary factors play a role in the development of PDAC in 3% to 5% of all patients. Surveillance of high-risk groups, may facilitate detection of PDAC at an early stage. The aim of this study was to assess whether surveillance aids detection of early-stage PDAC or precursor lesions (PRLs) and improves the prognosis.\nPATIENTS AND METHODS: Screening outcomes were collected from three European centers that conduct prospective screening in high-risk groups including families with clustering of PDAC (familial pancreatic cancer [FPC]) or families with a gene defect that predisposes to PDAC. The surveillance program consisted of annual magnetic resonance imaging, magnetic resonance cholangiopancreatography, and/or endoscopic ultrasound.\nRESULTS: Four hundred eleven asymptomatic individuals participated in the surveillance programs, including 178 CDKN2A mutation carriers, 214 individuals with FPC, and 19 BRCA1/2 or PALB2 mutation carriers. PDAC was detected in 13 (7.3%) of 178 CDKN2A mutation carriers. The resection rate was 75%, and the 5-year survival rate was 24%. Two CDKN2A mutation carriers (1%) underwent surgical resection for low-risk PRL. Two individuals (0.9%) in the FPC cohort had a pancreatic tumor, including one advanced PDAC and one early grade 2 neuroendocrine tumor. Thirteen individuals with FPC (6.1%) underwent surgical resection for a suspected PRL, but only four (1.9%) had high-risk lesions (ie, high-grade intraductal papillary mucinous neoplasms or grade 3 pancreatic intraepithelial neoplasms). One BRCA2 mutation carrier was found to have PDAC, and another BRCA2 mutation carrier and a PALB2 mutation carrier underwent surgery and were found to have low-risk PRL. No serious complications occurred as consequence of the program.\nCONCLUSION: Surveillance of CDNK2A mutation carriers is relatively successful, detecting most PDACs at a resectable stage. The benefit of surveillance in families with FPC is less evident.","DOI":"10.1200/JCO.2015.64.0730","ISSN":"1527-7755","note":"PMID: 27114589","title-short":"Benefit of Surveillance for Pancreatic Cancer in High-Risk Individuals","journalAbbreviation":"J. Clin. Oncol.","language":"eng","author":[{"family":"Vasen","given":"Hans"},{"family":"Ibrahim","given":"Isaura"},{"family":"Ponce","given":"Carmen Guillen"},{"family":"Slater","given":"Emily P."},{"family":"Matth?i","given":"Elvira"},{"family":"Carrato","given":"Alfredo"},{"family":"Earl","given":"Julie"},{"family":"Robbers","given":"Kristin"},{"family":"Mil","given":"Anneke M.","non-dropping-particle":"van"},{"family":"Potjer","given":"Thomas"},{"family":"Bonsing","given":"Bert A."},{"family":"Vos Tot Nederveen Cappel","given":"Wouter H.","non-dropping-particle":"de"},{"family":"Bergman","given":"Wilma"},{"family":"Wasser","given":"Martin"},{"family":"Morreau","given":"Hans"},{"family":"Kl?ppel","given":"Günter"},{"family":"Schicker","given":"Christoph"},{"family":"Steinkamp","given":"Martin"},{"family":"Figiel","given":"Jens"},{"family":"Esposito","given":"Irene"},{"family":"Mocci","given":"Evelina"},{"family":"Vazquez-Sequeiros","given":"Enrique"},{"family":"Sanjuanbenito","given":"Alfonso"},{"family":"Mu?oz-Beltran","given":"Maria"},{"family":"Montans","given":"José"},{"family":"Langer","given":"Peter"},{"family":"Fendrich","given":"Volker"},{"family":"Bartsch","given":"Detlef K."}],"issued":{"date-parts":[["2016"]],"season":"10"}}},{"id":"BbVydael/S8JLwcaf","uris":[""],"uri":[""],"itemData":{"id":63,"type":"article-journal","title":"Screening for pancreatic cancer in a high-risk cohort: an eight-year experience","container-title":"Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract","page":"771-783","volume":"16","issue":"4","source":"PubMed","abstract":"BACKGROUND: Pancreatic adenocarcinoma is the fourth leading cause of cancer death.\nMETHODS: A prospective cohort study was undertaken between 2003 and 2011 at a tertiary care centre in Toronto, Canada. Two hundred and sixty-two subjects were enrolled based on an elevated estimated lifetime risk for pancreatic cancer due to known genetic mutations and/or cancer family history. Subjects underwent annual magnetic resonance imaging, followed by additional investigations if abnormal findings were detected. Evidence of malignancy or suspicious macroscopic abnormalities prompted referral for surgical intervention.\nRESULTS: Average length of follow-up was 4.2 years, during which 84/262 (32%) subjects demonstrated pancreatic abnormalities. Three participants developed pancreatic adenocarcinoma (one 1.5-cm tumor was resected but recurred, while the other two subjects developed metastatic cancer), and a fourth participant developed a pancreatic neuroendocrine tumor that was resected. Fifteen subjects had radiologic evidence of branch-duct intraductal papillary mucinous neoplasms, of which two underwent surgical resection. Sixty-five subjects had simple pancreatic cysts that have remained stable.\nCONCLUSION: Magnetic resonance imaging can detect small pancreatic tumors and cystic lesions, but further improvement in sensitivity is needed. An understanding of the natural history of pre-invasive lesions in members of high-risk families is necessary for developing a more effective screening program.","DOI":"10.1007/s11605-011-1781-6","ISSN":"1873-4626","note":"PMID: 22127781","title-short":"Screening for pancreatic cancer in a high-risk cohort","journalAbbreviation":"J. Gastrointest. Surg.","language":"eng","author":[{"family":"Al-Sukhni","given":"Wigdan"},{"family":"Borgida","given":"Ayelet"},{"family":"Rothenmund","given":"Heidi"},{"family":"Holter","given":"Spring"},{"family":"Semotiuk","given":"Kara"},{"family":"Grant","given":"Robert"},{"family":"Wilson","given":"Stephanie"},{"family":"Moore","given":"Malcolm"},{"family":"Narod","given":"Steven"},{"family":"Jhaveri","given":"Kartik"},{"family":"Haider","given":"Masoom A."},{"family":"Gallinger","given":"Steven"}],"issued":{"date-parts":[["2012",4]]}}}],"schema":""} [23,31,32]. The frequency of subsequent follow-up examinations varies depending on different studies and recommendations ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"yBkItEiD","properties":{"formattedCitation":"\\super [4,30\\uc0\\u8211{}34]\\nosupersub{}","plainCitation":"[4,30–34]","noteIndex":0},"citationItems":[{"id":"BbVydael/zZTZnNXC","uris":[""],"uri":[""],"itemData":{"id":36,"type":"article-journal","title":"Refinement of screening for familial pancreatic cancer","container-title":"Gut","page":"1314-1321","volume":"65","issue":"8","source":"PubMed","abstract":"OBJECTIVE: Surveillance programmes are recommended for individuals at risk (IAR) of familial pancreatic cancer (FPC) to detect early pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC). However, the age to begin screening and the optimal screening protocol remain to be determined.\nMETHODS: IAR from non-CDKN2A FPC families underwent annual screening by MRI with endoscopic ultrasonography (EUS) in board-approved prospective screening programmes at three tertiary referral centres. The diagnostic yield according to age and different screening protocols was analysed.\nRESULTS: 253 IAR with a median age of 48 (25-81)?years underwent screening with a median of 3 (1-11) screening visits during a median follow-up of 28 (1-152)?months. 134 (53%) IAR revealed pancreatic lesions on imaging, mostly cystic (94%), on baseline or follow-up screening. Lesions were significantly more often identified in IAR above the age of 45?years (p<0.0001). In 21 IAR who underwent surgery, no significant lesions (PDAC, pancreatic intraepithelial neoplasia (PanIN) 3 lesions, high-grade intraductal papillary mucinous neoplasia (IPMN)) were detected before the age of 50?years. Potentially relevant lesions (multifocal PanIN2 lesions, low/moderate-grade branch-duct IPMNs) occurred also significantly more often after the age of 50?years (13 vs 2, p<0.0004). The diagnostic yield of potentially relevant lesions was not different between screening protocols using annual MRI with EUS (n=98) or annual MRI with EUS every 3rd year (n=198) and between IAR screened at intervals of 12?months (n=180) or IAR that decided to be screened at ≥24?months intervals (n=30).\nCONCLUSIONS: It appears safe to start screening for PDAC in IAR of non-CDKN2a FPC families at the age of 50?years. MRI-based screening supplemented by EUS at baseline and every 3rd year or when changes in MRI occur appears to be efficient.","DOI":"10.1136/gutjnl-2015-311098","ISSN":"1468-3288","note":"PMID: 27222532","journalAbbreviation":"Gut","language":"eng","author":[{"family":"Bartsch","given":"D. K."},{"family":"Slater","given":"E. P."},{"family":"Carrato","given":"A."},{"family":"Ibrahim","given":"I. S."},{"family":"Guillen-Ponce","given":"C."},{"family":"Vasen","given":"H. F. A."},{"family":"Matth?i","given":"E."},{"family":"Earl","given":"J."},{"family":"Jendryschek","given":"F. S."},{"family":"Figiel","given":"J."},{"family":"Steinkamp","given":"M."},{"family":"Ramaswamy","given":"A."},{"family":"Vázquez-Sequeiros","given":"E."},{"family":"Mu?oz-Beltran","given":"M."},{"family":"Montans","given":"J."},{"family":"Mocci","given":"E."},{"family":"Bonsing","given":"B. A."},{"family":"Wasser","given":"M."},{"family":"Kl?ppel","given":"G."},{"family":"Langer","given":"P."},{"family":"Fendrich","given":"V."},{"family":"Gress","given":"T. M."}],"issued":{"date-parts":[["2016"]]}}},{"id":"BbVydael/HMFnecr3","uris":[""],"uri":[""],"itemData":{"id":31,"type":"article-journal","title":"Risk of Neoplastic Progression in Individuals at High Risk for Pancreatic Cancer Undergoing Long-term Surveillance","container-title":"Gastroenterology","page":"740-751.e2","volume":"155","issue":"3","source":"PubMed","abstract":"BACKGROUND & AIMS: Screening of individuals who have a high risk of pancreatic ductal adenocarcinoma (PDAC), because of genetic factors, frequently leads to identification of pancreatic lesions. We investigated the incidence of PDAC and risk factors for neoplastic progression in individuals at high risk for PDAC enrolled in a long-term screening study.\nMETHODS: We analyzed data from 354 individuals at high risk for PDAC (based on genetic factors of family history), enrolled in Cancer of the Pancreas Screening cohort studies at tertiary care academic centers from 1998 through 2014 (median follow-up time, 5.6 years). All subjects were evaluated at study entry (baseline) by endoscopic ultrasonography and underwent surveillance with endoscopic ultrasonography, magnetic resonance imaging, and/or computed tomography. The primary endpoint was the cumulative incidence of PDAC, pancreatic intraepithelial neoplasia grade 3, or intraductal papillary mucinous neoplasm with high-grade dysplasia (HGD) after baseline. We performed multivariate Cox regression and Kaplan-Meier analyses.\nRESULTS: During the follow-up period, pancreatic lesions with worrisome features (solid mass, multiple cysts, cyst size > 3 cm, thickened/enhancing walls, mural nodule, dilated main pancreatic duct > 5 mm, or abrupt change in duct caliber) or rapid cyst growth (>4 mm/year) were detected in 68 patients (19%). Overall, 24 of 354 patients (7%) had neoplastic progression (14 PDACs and 10 HGDs) over a 16-year period; the rate of progression was 1.6%/year, and 93% had detectable lesions with worrisome features before diagnosis of the PDAC or HGD. Nine of the 10 PDACs detected during routine surveillance were resectable; a significantly higher proportion of patients with resectable PDACs survived 3?years (85%) compared with the 4 subjects with symptomatic, unresectable PDACs (25%), which developed outside surveillance (log rank P < .0001). Neoplastic progression occurred at a median age of 67 years; the median time from baseline screening until PDAC diagnosis was 4.8 years (interquartile range, 1.6-6.9 years).\nCONCLUSIONS: In a long-term (16-year) follow-up study of individuals at high-risk for PDAC, we found most PDACs detected during surveillance (9/10) to be resectable, and 85% of these patients survived for 3 years. We?identified radiologic features associated with neoplastic progression.","DOI":"10.1053/j.gastro.2018.05.035","ISSN":"1528-0012","note":"PMID: 29803839\nPMCID: PMC6120797","journalAbbreviation":"Gastroenterology","language":"eng","author":[{"family":"Canto","given":"Marcia Irene"},{"family":"Almario","given":"Jose Alejandro"},{"family":"Schulick","given":"Richard D."},{"family":"Yeo","given":"Charles J."},{"family":"Klein","given":"Alison"},{"family":"Blackford","given":"Amanda"},{"family":"Shin","given":"Eun Ji"},{"family":"Sanyal","given":"Abanti"},{"family":"Yenokyan","given":"Gayane"},{"family":"Lennon","given":"Anne Marie"},{"family":"Kamel","given":"Ihab R."},{"family":"Fishman","given":"Elliot K."},{"family":"Wolfgang","given":"Christopher"},{"family":"Weiss","given":"Matthew"},{"family":"Hruban","given":"Ralph H."},{"family":"Goggins","given":"Michael"}],"issued":{"date-parts":[["2018"]]}}},{"id":"BbVydael/Sm6GTEmo","uris":[""],"uri":[""],"itemData":{"id":70,"type":"article-journal","title":"Benefit of Surveillance for Pancreatic Cancer in High-Risk Individuals: Outcome of Long-Term Prospective Follow-Up Studies From Three European Expert Centers","container-title":"Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology","page":"2010-2019","volume":"34","issue":"17","source":"PubMed","abstract":"PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis. Hereditary factors play a role in the development of PDAC in 3% to 5% of all patients. Surveillance of high-risk groups, may facilitate detection of PDAC at an early stage. The aim of this study was to assess whether surveillance aids detection of early-stage PDAC or precursor lesions (PRLs) and improves the prognosis.\nPATIENTS AND METHODS: Screening outcomes were collected from three European centers that conduct prospective screening in high-risk groups including families with clustering of PDAC (familial pancreatic cancer [FPC]) or families with a gene defect that predisposes to PDAC. The surveillance program consisted of annual magnetic resonance imaging, magnetic resonance cholangiopancreatography, and/or endoscopic ultrasound.\nRESULTS: Four hundred eleven asymptomatic individuals participated in the surveillance programs, including 178 CDKN2A mutation carriers, 214 individuals with FPC, and 19 BRCA1/2 or PALB2 mutation carriers. PDAC was detected in 13 (7.3%) of 178 CDKN2A mutation carriers. The resection rate was 75%, and the 5-year survival rate was 24%. Two CDKN2A mutation carriers (1%) underwent surgical resection for low-risk PRL. Two individuals (0.9%) in the FPC cohort had a pancreatic tumor, including one advanced PDAC and one early grade 2 neuroendocrine tumor. Thirteen individuals with FPC (6.1%) underwent surgical resection for a suspected PRL, but only four (1.9%) had high-risk lesions (ie, high-grade intraductal papillary mucinous neoplasms or grade 3 pancreatic intraepithelial neoplasms). One BRCA2 mutation carrier was found to have PDAC, and another BRCA2 mutation carrier and a PALB2 mutation carrier underwent surgery and were found to have low-risk PRL. No serious complications occurred as consequence of the program.\nCONCLUSION: Surveillance of CDNK2A mutation carriers is relatively successful, detecting most PDACs at a resectable stage. The benefit of surveillance in families with FPC is less evident.","DOI":"10.1200/JCO.2015.64.0730","ISSN":"1527-7755","note":"PMID: 27114589","title-short":"Benefit of Surveillance for Pancreatic Cancer in High-Risk Individuals","journalAbbreviation":"J. Clin. Oncol.","language":"eng","author":[{"family":"Vasen","given":"Hans"},{"family":"Ibrahim","given":"Isaura"},{"family":"Ponce","given":"Carmen Guillen"},{"family":"Slater","given":"Emily P."},{"family":"Matth?i","given":"Elvira"},{"family":"Carrato","given":"Alfredo"},{"family":"Earl","given":"Julie"},{"family":"Robbers","given":"Kristin"},{"family":"Mil","given":"Anneke M.","non-dropping-particle":"van"},{"family":"Potjer","given":"Thomas"},{"family":"Bonsing","given":"Bert A."},{"family":"Vos Tot Nederveen Cappel","given":"Wouter H.","non-dropping-particle":"de"},{"family":"Bergman","given":"Wilma"},{"family":"Wasser","given":"Martin"},{"family":"Morreau","given":"Hans"},{"family":"Kl?ppel","given":"Günter"},{"family":"Schicker","given":"Christoph"},{"family":"Steinkamp","given":"Martin"},{"family":"Figiel","given":"Jens"},{"family":"Esposito","given":"Irene"},{"family":"Mocci","given":"Evelina"},{"family":"Vazquez-Sequeiros","given":"Enrique"},{"family":"Sanjuanbenito","given":"Alfonso"},{"family":"Mu?oz-Beltran","given":"Maria"},{"family":"Montans","given":"José"},{"family":"Langer","given":"Peter"},{"family":"Fendrich","given":"Volker"},{"family":"Bartsch","given":"Detlef K."}],"issued":{"date-parts":[["2016"]],"season":"10"}}},{"id":"BbVydael/S8JLwcaf","uris":[""],"uri":[""],"itemData":{"id":63,"type":"article-journal","title":"Screening for pancreatic cancer in a high-risk cohort: an eight-year experience","container-title":"Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract","page":"771-783","volume":"16","issue":"4","source":"PubMed","abstract":"BACKGROUND: Pancreatic adenocarcinoma is the fourth leading cause of cancer death.\nMETHODS: A prospective cohort study was undertaken between 2003 and 2011 at a tertiary care centre in Toronto, Canada. Two hundred and sixty-two subjects were enrolled based on an elevated estimated lifetime risk for pancreatic cancer due to known genetic mutations and/or cancer family history. Subjects underwent annual magnetic resonance imaging, followed by additional investigations if abnormal findings were detected. Evidence of malignancy or suspicious macroscopic abnormalities prompted referral for surgical intervention.\nRESULTS: Average length of follow-up was 4.2 years, during which 84/262 (32%) subjects demonstrated pancreatic abnormalities. Three participants developed pancreatic adenocarcinoma (one 1.5-cm tumor was resected but recurred, while the other two subjects developed metastatic cancer), and a fourth participant developed a pancreatic neuroendocrine tumor that was resected. Fifteen subjects had radiologic evidence of branch-duct intraductal papillary mucinous neoplasms, of which two underwent surgical resection. Sixty-five subjects had simple pancreatic cysts that have remained stable.\nCONCLUSION: Magnetic resonance imaging can detect small pancreatic tumors and cystic lesions, but further improvement in sensitivity is needed. An understanding of the natural history of pre-invasive lesions in members of high-risk families is necessary for developing a more effective screening program.","DOI":"10.1007/s11605-011-1781-6","ISSN":"1873-4626","note":"PMID: 22127781","title-short":"Screening for pancreatic cancer in a high-risk cohort","journalAbbreviation":"J. Gastrointest. Surg.","language":"eng","author":[{"family":"Al-Sukhni","given":"Wigdan"},{"family":"Borgida","given":"Ayelet"},{"family":"Rothenmund","given":"Heidi"},{"family":"Holter","given":"Spring"},{"family":"Semotiuk","given":"Kara"},{"family":"Grant","given":"Robert"},{"family":"Wilson","given":"Stephanie"},{"family":"Moore","given":"Malcolm"},{"family":"Narod","given":"Steven"},{"family":"Jhaveri","given":"Kartik"},{"family":"Haider","given":"Masoom A."},{"family":"Gallinger","given":"Steven"}],"issued":{"date-parts":[["2012",4]]}}},{"id":"BbVydael/ujvJfaIr","uris":[""],"uri":[""],"itemData":{"id":52,"type":"article-journal","title":"Pancreatic cancer screening in a prospective cohort of high-risk patients: a comprehensive strategy of imaging and genetics","container-title":"Clinical Cancer Research: An Official Journal of the American Association for Cancer Research","page":"5028-5037","volume":"16","issue":"20","source":"PubMed","abstract":"PURPOSE: Pancreatic cancer is a virtually uniformly fatal disease. We aimed to determine if screening to identify curable neoplasms is effective when offered to patients at high risk.\nEXPERIMENTAL DESIGN: Patients at high risk of pancreatic cancer were prospectively enrolled into a screening program. Endoscopic ultrasound (EUS), magnetic resonance imaging (MRI), and genetic testing were offered by a multidisciplinary team according to each patient's risk.\nRESULTS: Fifty-one patients in 43 families were enrolled, with mean age of 52 years, 35% of whom were male. Of these patients, 31 underwent EUS and 33 MRI. EUS revealed two patients with pancreatic cancer (one resectable, one metastatic), five with intraductal papillary mucinous neoplasms (IPMN), seven with cysts, and six with parenchymal changes. Five had pancreatic surgery (one total pancreatectomy for pancreatic cancer, three distal and one central pancreatectomy for pancreatic intraepithelial neoplasia 2 and IPMN). A total of 24 (47%) had genetic testing (19 for BRCA1/2 mutations, 4 for CDKN2A, 1 for MLH1/MSH2) and 7 were positive for BRCA1/2 mutations. Four extrapancreatic neoplasms were found: two ovarian cancers on prophylactic total abdominal hysterectomy and bilateral salpingo-oophorectomy, one carcinoid, and one papillary thyroid carcinoma. Overall, 6 (12%) of the 51 patients had neoplastic lesions in the pancreas and 9 (18%) had neoplasms in any location. All were on the initial round of screening. All patients remain alive and without complications of screening.\nCONCLUSIONS: Pancreatic cancer screening for high-risk patients with a comprehensive strategy of imaging and genetics is effective and identifies curable neoplasms that can be resected. Ongoing study will better define who will benefit from screening and what screening strategy will be the most effective.","DOI":"10.1158/1078-R-09-3209","ISSN":"1078-0432","note":"PMID: 20876795","title-short":"Pancreatic cancer screening in a prospective cohort of high-risk patients","journalAbbreviation":"Clin. Cancer Res.","language":"eng","author":[{"family":"Verna","given":"Elizabeth C."},{"family":"Hwang","given":"Caroline"},{"family":"Stevens","given":"Peter D."},{"family":"Rotterdam","given":"Heidrun"},{"family":"Stavropoulos","given":"Stavros N."},{"family":"Sy","given":"Carolyn D."},{"family":"Prince","given":"Martin A."},{"family":"Chung","given":"Wendy K."},{"family":"Fine","given":"Robert L."},{"family":"Chabot","given":"John A."},{"family":"Frucht","given":"Harold"}],"issued":{"date-parts":[["2010",10,15]]}}},{"id":"BbVydael/bbEwgRsE","uris":[""],"uri":[""],"itemData":{"id":67,"type":"article-journal","title":"Feasibility and yield of screening in relatives from familial pancreatic cancer families","container-title":"The American Journal of Gastroenterology","page":"946-954","volume":"106","issue":"5","source":"PubMed","abstract":"OBJECTIVES: Pancreatic adenocarcinoma is a lethal disease. Over 80% of patients are found to have metastatic disease at the time of diagnosis. Strategies to improve disease-specific outcome include identification and early detection of precursor lesions or early cancers in high-risk groups. In this study, we investigate whether screening at-risk relatives of familial pancreatic cancer (FPC) patients is safe and has significant yield.\nMETHODS: We enrolled 309 asymptomatic at-risk relatives into our Familial Pancreatic Tumor Registry (FPTR) and offered them screening with magnetic resonance cholangiopancreaticogram (MRCP) followed by endoscopic ultrasound (EUS) with fine needle aspiration if indicated. Relatives with findings were referred for surgical evaluation.\nRESULTS: As of 1 August 2009, 109 relatives had completed at least one cycle of screening. Abnormal radiographic findings were present on initial screening in 18/109 patients (16.5%), 15 of whom underwent EUS. A significant abnormality was confirmed in 9 of 15 patients, 6 of whom ultimately had surgery for an overall diagnostic yield of 8.3% (9/109). Yield was greatest in relatives >65 years old (35%, 6/17) when compared with relatives 55-65 years (3%, 1/31) and relatives <55 years (3%, 2/61).\nCONCLUSIONS: Screening at-risk relatives from FPC families has a significant diagnostic yield, particularly in relatives >65 years of age, confirming prior studies. MRCP as initial screening modality is safe and effective.","DOI":"10.1038/ajg.2011.65","ISSN":"1572-0241","note":"PMID: 21468009\nPMCID: PMC3683863","journalAbbreviation":"Am. J. Gastroenterol.","language":"eng","author":[{"family":"Ludwig","given":"Emmy"},{"family":"Olson","given":"Sara H."},{"family":"Bayuga","given":"Sharon"},{"family":"Simon","given":"Jennifer"},{"family":"Schattner","given":"Mark A."},{"family":"Gerdes","given":"Hans"},{"family":"Allen","given":"Peter J."},{"family":"Jarnagin","given":"William R."},{"family":"Kurtz","given":"Robert C."}],"issued":{"date-parts":[["2011",5]]}}}],"schema":""} [4,30–34]. Several multicenter studies have compared different surveillance protocols (e.g. annual MRI and EUS or annual MRI with EUS every 3 years) and did not find any difference in terms of number of diagnosed lesions ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"YqTRB8A8","properties":{"formattedCitation":"\\super [4,31]\\nosupersub{}","plainCitation":"[4,31]","noteIndex":0},"citationItems":[{"id":"BbVydael/zZTZnNXC","uris":[""],"uri":[""],"itemData":{"id":36,"type":"article-journal","title":"Refinement of screening for familial pancreatic cancer","container-title":"Gut","page":"1314-1321","volume":"65","issue":"8","source":"PubMed","abstract":"OBJECTIVE: Surveillance programmes are recommended for individuals at risk (IAR) of familial pancreatic cancer (FPC) to detect early pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC). However, the age to begin screening and the optimal screening protocol remain to be determined.\nMETHODS: IAR from non-CDKN2A FPC families underwent annual screening by MRI with endoscopic ultrasonography (EUS) in board-approved prospective screening programmes at three tertiary referral centres. The diagnostic yield according to age and different screening protocols was analysed.\nRESULTS: 253 IAR with a median age of 48 (25-81)?years underwent screening with a median of 3 (1-11) screening visits during a median follow-up of 28 (1-152)?months. 134 (53%) IAR revealed pancreatic lesions on imaging, mostly cystic (94%), on baseline or follow-up screening. Lesions were significantly more often identified in IAR above the age of 45?years (p<0.0001). In 21 IAR who underwent surgery, no significant lesions (PDAC, pancreatic intraepithelial neoplasia (PanIN) 3 lesions, high-grade intraductal papillary mucinous neoplasia (IPMN)) were detected before the age of 50?years. Potentially relevant lesions (multifocal PanIN2 lesions, low/moderate-grade branch-duct IPMNs) occurred also significantly more often after the age of 50?years (13 vs 2, p<0.0004). The diagnostic yield of potentially relevant lesions was not different between screening protocols using annual MRI with EUS (n=98) or annual MRI with EUS every 3rd year (n=198) and between IAR screened at intervals of 12?months (n=180) or IAR that decided to be screened at ≥24?months intervals (n=30).\nCONCLUSIONS: It appears safe to start screening for PDAC in IAR of non-CDKN2a FPC families at the age of 50?years. MRI-based screening supplemented by EUS at baseline and every 3rd year or when changes in MRI occur appears to be efficient.","DOI":"10.1136/gutjnl-2015-311098","ISSN":"1468-3288","note":"PMID: 27222532","journalAbbreviation":"Gut","language":"eng","author":[{"family":"Bartsch","given":"D. K."},{"family":"Slater","given":"E. P."},{"family":"Carrato","given":"A."},{"family":"Ibrahim","given":"I. S."},{"family":"Guillen-Ponce","given":"C."},{"family":"Vasen","given":"H. F. A."},{"family":"Matth?i","given":"E."},{"family":"Earl","given":"J."},{"family":"Jendryschek","given":"F. S."},{"family":"Figiel","given":"J."},{"family":"Steinkamp","given":"M."},{"family":"Ramaswamy","given":"A."},{"family":"Vázquez-Sequeiros","given":"E."},{"family":"Mu?oz-Beltran","given":"M."},{"family":"Montans","given":"J."},{"family":"Mocci","given":"E."},{"family":"Bonsing","given":"B. A."},{"family":"Wasser","given":"M."},{"family":"Kl?ppel","given":"G."},{"family":"Langer","given":"P."},{"family":"Fendrich","given":"V."},{"family":"Gress","given":"T. M."}],"issued":{"date-parts":[["2016"]]}}},{"id":"BbVydael/Sm6GTEmo","uris":[""],"uri":[""],"itemData":{"id":70,"type":"article-journal","title":"Benefit of Surveillance for Pancreatic Cancer in High-Risk Individuals: Outcome of Long-Term Prospective Follow-Up Studies From Three European Expert Centers","container-title":"Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology","page":"2010-2019","volume":"34","issue":"17","source":"PubMed","abstract":"PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis. Hereditary factors play a role in the development of PDAC in 3% to 5% of all patients. Surveillance of high-risk groups, may facilitate detection of PDAC at an early stage. The aim of this study was to assess whether surveillance aids detection of early-stage PDAC or precursor lesions (PRLs) and improves the prognosis.\nPATIENTS AND METHODS: Screening outcomes were collected from three European centers that conduct prospective screening in high-risk groups including families with clustering of PDAC (familial pancreatic cancer [FPC]) or families with a gene defect that predisposes to PDAC. The surveillance program consisted of annual magnetic resonance imaging, magnetic resonance cholangiopancreatography, and/or endoscopic ultrasound.\nRESULTS: Four hundred eleven asymptomatic individuals participated in the surveillance programs, including 178 CDKN2A mutation carriers, 214 individuals with FPC, and 19 BRCA1/2 or PALB2 mutation carriers. PDAC was detected in 13 (7.3%) of 178 CDKN2A mutation carriers. The resection rate was 75%, and the 5-year survival rate was 24%. Two CDKN2A mutation carriers (1%) underwent surgical resection for low-risk PRL. Two individuals (0.9%) in the FPC cohort had a pancreatic tumor, including one advanced PDAC and one early grade 2 neuroendocrine tumor. Thirteen individuals with FPC (6.1%) underwent surgical resection for a suspected PRL, but only four (1.9%) had high-risk lesions (ie, high-grade intraductal papillary mucinous neoplasms or grade 3 pancreatic intraepithelial neoplasms). One BRCA2 mutation carrier was found to have PDAC, and another BRCA2 mutation carrier and a PALB2 mutation carrier underwent surgery and were found to have low-risk PRL. No serious complications occurred as consequence of the program.\nCONCLUSION: Surveillance of CDNK2A mutation carriers is relatively successful, detecting most PDACs at a resectable stage. The benefit of surveillance in families with FPC is less evident.","DOI":"10.1200/JCO.2015.64.0730","ISSN":"1527-7755","note":"PMID: 27114589","title-short":"Benefit of Surveillance for Pancreatic Cancer in High-Risk Individuals","journalAbbreviation":"J. Clin. Oncol.","language":"eng","author":[{"family":"Vasen","given":"Hans"},{"family":"Ibrahim","given":"Isaura"},{"family":"Ponce","given":"Carmen Guillen"},{"family":"Slater","given":"Emily P."},{"family":"Matth?i","given":"Elvira"},{"family":"Carrato","given":"Alfredo"},{"family":"Earl","given":"Julie"},{"family":"Robbers","given":"Kristin"},{"family":"Mil","given":"Anneke M.","non-dropping-particle":"van"},{"family":"Potjer","given":"Thomas"},{"family":"Bonsing","given":"Bert A."},{"family":"Vos Tot Nederveen Cappel","given":"Wouter H.","non-dropping-particle":"de"},{"family":"Bergman","given":"Wilma"},{"family":"Wasser","given":"Martin"},{"family":"Morreau","given":"Hans"},{"family":"Kl?ppel","given":"Günter"},{"family":"Schicker","given":"Christoph"},{"family":"Steinkamp","given":"Martin"},{"family":"Figiel","given":"Jens"},{"family":"Esposito","given":"Irene"},{"family":"Mocci","given":"Evelina"},{"family":"Vazquez-Sequeiros","given":"Enrique"},{"family":"Sanjuanbenito","given":"Alfonso"},{"family":"Mu?oz-Beltran","given":"Maria"},{"family":"Montans","given":"José"},{"family":"Langer","given":"Peter"},{"family":"Fendrich","given":"Volker"},{"family":"Bartsch","given":"Detlef K."}],"issued":{"date-parts":[["2016"]],"season":"10"}}}],"schema":""} [4,31]. However, these studies compared the total number of diagnosed lesions, whereas only the number of (pre)malignant lesions would have had clinical relevance. Nevertheless, and unless demonstrated otherwise, it seems reasonable to perform one MRI and one EUS examination per year in HRI ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"iSuF9dtI","properties":{"formattedCitation":"\\super [11,19,31,32]\\nosupersub{}","plainCitation":"[11,19,31,32]","noteIndex":0},"citationItems":[{"id":"BbVydael/iMJ7y1A2","uris":[""],"uri":[""],"itemData":{"id":33,"type":"article-journal","title":"Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma: a patient-level meta-analysis and proposition of the Beaujon score","container-title":"United European Gastroenterology Journal","page":"205064061882491","source":"Crossref","DOI":"10.1177/2050640618824910","ISSN":"2050-6406, 2050-6414","title-short":"Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma","language":"en","author":[{"family":"Mestier","given":"Louis","non-dropping-particle":"de"},{"family":"Muller","given":"Marie"},{"family":"Cros","given":"Jér?me"},{"family":"Vullierme","given":"Marie-Pierre"},{"family":"Vernerey","given":"Dewi"},{"family":"Maire","given":"Frédérique"},{"family":"Dokmak","given":"Safi"},{"family":"Rebours","given":"Vinciane"},{"family":"Sauvanet","given":"Alain"},{"family":"Lévy","given":"Philippe"},{"family":"Hammel","given":"Pascal"}],"issued":{"date-parts":[["2019",1,12]]}}},{"id":"BbVydael/39vT8LTF","uris":[""],"uri":[""],"itemData":{"id":98,"type":"article-journal","title":"Diagnostic Yield From Screening Asymptomatic Individuals at?High Risk for Pancreatic Cancer: A Meta-analysis of Cohort?Studies","container-title":"Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association","page":"41-53","volume":"17","issue":"1","source":"PubMed","abstract":"BACKGROUND & AIMS: There have been few studies of abdominal imaging screening of individuals at high risk for pancreatic cancer (based on family history or genetic variants). We performed a meta-analysis of prospective cohort studies to determine the diagnostic yield and outcomes of abdominal imaging screening for asymptomatic individuals at high risk.\nMETHODS: Through a systematic review of multiple electronic databases and conference proceedings through July 2017, we identified prospective cohort studies (>20 patients) of asymptomatic adults determined to be at high-risk of pancreatic cancer (lifetime risk >5%, including specific genetic-associated conditions) who were screened by endoscopic ultrasound (EUS) and/or magnetic resonance imaging (MRI) to detect pancreatic lesions. Our primary outcome was identification of high-risk pancreatic lesions (high-grade pancreatic intraepithelial neoplasia, high-grade dysplasia, or adenocarcinoma) at initial screening, and overall incidence during follow up. Summary estimates were reported as incidence rates per 100 patient-years.\nRESULTS: We identified 19 studies comprising 7085 individuals at high risk for pancreatic cancer; of these, 1660 patients were evaluated by EUS and/or MRI. Fifty-nine high-risk lesions were identified (43 adenocarcinomas: 28 during the initial exam and 15 during follow-up surveillance) and 257 patients underwent pancreatic surgery. Based on our meta-analysis, the overall diagnostic yield screening for high-risk pancreatic lesions was 0.74 (95% CI, 0.33-1.14), with moderate heterogeneity among studies. The number needed to screen to identify 1 patient with?a high-risk lesion was 135 (95% CI, 88-303). The diagnostic yield was similar for patients with different genetic features that increased risk, and whether patients were screened by EUS or MRI.\nCONCLUSIONS: Based on meta-analysis, 135 patients at high-risk for pancreatic cancer must be screened to identify 1 patient with a high-risk pancreatic lesion. Further studies are needed to determine whether screening reduces mortality and is cost effectiveness for individuals at high-risk of pancreatic cancer.","DOI":"10.1016/j.cgh.2018.04.065","ISSN":"1542-7714","note":"PMID: 29775792","title-short":"Diagnostic Yield From Screening Asymptomatic Individuals at?High Risk for Pancreatic Cancer","journalAbbreviation":"Clin. Gastroenterol. Hepatol.","language":"eng","author":[{"family":"Corral","given":"Juan E."},{"family":"Mareth","given":"Karl F."},{"family":"Riegert-Johnson","given":"Douglas L."},{"family":"Das","given":"Ananya"},{"family":"Wallace","given":"Michael B."}],"issued":{"date-parts":[["2019",1]]}}},{"id":"BbVydael/Sm6GTEmo","uris":[""],"uri":[""],"itemData":{"id":70,"type":"article-journal","title":"Benefit of Surveillance for Pancreatic Cancer in High-Risk Individuals: Outcome of Long-Term Prospective Follow-Up Studies From Three European Expert Centers","container-title":"Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology","page":"2010-2019","volume":"34","issue":"17","source":"PubMed","abstract":"PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis. Hereditary factors play a role in the development of PDAC in 3% to 5% of all patients. Surveillance of high-risk groups, may facilitate detection of PDAC at an early stage. The aim of this study was to assess whether surveillance aids detection of early-stage PDAC or precursor lesions (PRLs) and improves the prognosis.\nPATIENTS AND METHODS: Screening outcomes were collected from three European centers that conduct prospective screening in high-risk groups including families with clustering of PDAC (familial pancreatic cancer [FPC]) or families with a gene defect that predisposes to PDAC. The surveillance program consisted of annual magnetic resonance imaging, magnetic resonance cholangiopancreatography, and/or endoscopic ultrasound.\nRESULTS: Four hundred eleven asymptomatic individuals participated in the surveillance programs, including 178 CDKN2A mutation carriers, 214 individuals with FPC, and 19 BRCA1/2 or PALB2 mutation carriers. PDAC was detected in 13 (7.3%) of 178 CDKN2A mutation carriers. The resection rate was 75%, and the 5-year survival rate was 24%. Two CDKN2A mutation carriers (1%) underwent surgical resection for low-risk PRL. Two individuals (0.9%) in the FPC cohort had a pancreatic tumor, including one advanced PDAC and one early grade 2 neuroendocrine tumor. Thirteen individuals with FPC (6.1%) underwent surgical resection for a suspected PRL, but only four (1.9%) had high-risk lesions (ie, high-grade intraductal papillary mucinous neoplasms or grade 3 pancreatic intraepithelial neoplasms). One BRCA2 mutation carrier was found to have PDAC, and another BRCA2 mutation carrier and a PALB2 mutation carrier underwent surgery and were found to have low-risk PRL. No serious complications occurred as consequence of the program.\nCONCLUSION: Surveillance of CDNK2A mutation carriers is relatively successful, detecting most PDACs at a resectable stage. The benefit of surveillance in families with FPC is less evident.","DOI":"10.1200/JCO.2015.64.0730","ISSN":"1527-7755","note":"PMID: 27114589","title-short":"Benefit of Surveillance for Pancreatic Cancer in High-Risk Individuals","journalAbbreviation":"J. Clin. Oncol.","language":"eng","author":[{"family":"Vasen","given":"Hans"},{"family":"Ibrahim","given":"Isaura"},{"family":"Ponce","given":"Carmen Guillen"},{"family":"Slater","given":"Emily P."},{"family":"Matth?i","given":"Elvira"},{"family":"Carrato","given":"Alfredo"},{"family":"Earl","given":"Julie"},{"family":"Robbers","given":"Kristin"},{"family":"Mil","given":"Anneke M.","non-dropping-particle":"van"},{"family":"Potjer","given":"Thomas"},{"family":"Bonsing","given":"Bert A."},{"family":"Vos Tot Nederveen Cappel","given":"Wouter H.","non-dropping-particle":"de"},{"family":"Bergman","given":"Wilma"},{"family":"Wasser","given":"Martin"},{"family":"Morreau","given":"Hans"},{"family":"Kl?ppel","given":"Günter"},{"family":"Schicker","given":"Christoph"},{"family":"Steinkamp","given":"Martin"},{"family":"Figiel","given":"Jens"},{"family":"Esposito","given":"Irene"},{"family":"Mocci","given":"Evelina"},{"family":"Vazquez-Sequeiros","given":"Enrique"},{"family":"Sanjuanbenito","given":"Alfonso"},{"family":"Mu?oz-Beltran","given":"Maria"},{"family":"Montans","given":"José"},{"family":"Langer","given":"Peter"},{"family":"Fendrich","given":"Volker"},{"family":"Bartsch","given":"Detlef K."}],"issued":{"date-parts":[["2016"]],"season":"10"}}},{"id":"BbVydael/S8JLwcaf","uris":[""],"uri":[""],"itemData":{"id":63,"type":"article-journal","title":"Screening for pancreatic cancer in a high-risk cohort: an eight-year experience","container-title":"Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract","page":"771-783","volume":"16","issue":"4","source":"PubMed","abstract":"BACKGROUND: Pancreatic adenocarcinoma is the fourth leading cause of cancer death.\nMETHODS: A prospective cohort study was undertaken between 2003 and 2011 at a tertiary care centre in Toronto, Canada. Two hundred and sixty-two subjects were enrolled based on an elevated estimated lifetime risk for pancreatic cancer due to known genetic mutations and/or cancer family history. Subjects underwent annual magnetic resonance imaging, followed by additional investigations if abnormal findings were detected. Evidence of malignancy or suspicious macroscopic abnormalities prompted referral for surgical intervention.\nRESULTS: Average length of follow-up was 4.2 years, during which 84/262 (32%) subjects demonstrated pancreatic abnormalities. Three participants developed pancreatic adenocarcinoma (one 1.5-cm tumor was resected but recurred, while the other two subjects developed metastatic cancer), and a fourth participant developed a pancreatic neuroendocrine tumor that was resected. Fifteen subjects had radiologic evidence of branch-duct intraductal papillary mucinous neoplasms, of which two underwent surgical resection. Sixty-five subjects had simple pancreatic cysts that have remained stable.\nCONCLUSION: Magnetic resonance imaging can detect small pancreatic tumors and cystic lesions, but further improvement in sensitivity is needed. An understanding of the natural history of pre-invasive lesions in members of high-risk families is necessary for developing a more effective screening program.","DOI":"10.1007/s11605-011-1781-6","ISSN":"1873-4626","note":"PMID: 22127781","title-short":"Screening for pancreatic cancer in a high-risk cohort","journalAbbreviation":"J. Gastrointest. Surg.","language":"eng","author":[{"family":"Al-Sukhni","given":"Wigdan"},{"family":"Borgida","given":"Ayelet"},{"family":"Rothenmund","given":"Heidi"},{"family":"Holter","given":"Spring"},{"family":"Semotiuk","given":"Kara"},{"family":"Grant","given":"Robert"},{"family":"Wilson","given":"Stephanie"},{"family":"Moore","given":"Malcolm"},{"family":"Narod","given":"Steven"},{"family":"Jhaveri","given":"Kartik"},{"family":"Haider","given":"Masoom A."},{"family":"Gallinger","given":"Steven"}],"issued":{"date-parts":[["2012",4]]}}}],"schema":""} [11,19,31,32].Life-long pancreatic follow-up is recommended in HRI, at least as long as patients remain fit for surgery, without severe comorbidities. In fact, there are no strong data to confirm when follow-up should be stopped ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"XZ4hzl4y","properties":{"formattedCitation":"\\super [17,23]\\nosupersub{}","plainCitation":"[17,23]","noteIndex":0},"citationItems":[{"id":"BbVydael/Cz27nE6J","uris":[""],"uri":[""],"itemData":{"id":17,"type":"article-journal","title":"Evaluating Susceptibility to Pancreatic Cancer: ASCO Clinical Practice Provisional Clinical Opinion Summary","container-title":"Journal of Oncology Practice","page":"108-111","volume":"15","issue":"2","source":"PubMed","DOI":"10.1200/JOP.18.00629","ISSN":"1935-469X","note":"PMID: 30589608","title-short":"Evaluating Susceptibility to Pancreatic Cancer","journalAbbreviation":"J Oncol Pract","language":"eng","author":[{"family":"Stoffel","given":"Elena M."},{"family":"McKernin","given":"Shannon E."},{"family":"Khorana","given":"Alok A."}],"issued":{"date-parts":[["2019",2]]}}},{"id":"BbVydael/NFPiCpG1","uris":[""],"uri":[""],"itemData":{"id":46,"type":"article-journal","title":"Screening for early pancreatic neoplasia in high-risk individuals: a prospective controlled study","container-title":"Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association","page":"766-781; quiz 665","volume":"4","issue":"6","source":"PubMed","abstract":"BACKGROUND & AIMS: Individuals with a strong family history of pancreatic cancer and persons with Peutz-Jeghers syndrome (PJS) have an increased risk for pancreatic cancer. This study screened for early pancreatic neoplasia and compared the pancreatic abnormalities in high-risk individuals and control subjects.\nMETHODS: High-risk individuals with PJS or a strong family history of pancreatic cancer were prospectively evaluated with baseline and 12-month computed tomography (CT) scan and endoscopic ultrasonography (EUS). If EUS was abnormal, EUS-fine-needle aspiration and endoscopic retrograde cholangiopancreatography (ERCP) were performed. Surgery was offered to patients with potentially neoplastic lesions. Radiologic findings and pathologic diagnoses were compared. Patients undergoing EUS and/or ERCP for benign non-pancreatic indications were concurrently enrolled as control subjects.\nRESULTS: Seventy-eight high-risk patients (72 from familial pancreatic cancer kindreds, 6 PJS) and 149 control patients were studied. To date, 8 patients with pancreatic neoplasia have been confirmed by surgery or fine-needle aspiration (10% yield of screening); 6 patients had 8 benign intraductal papillary mucinous neoplasms (IPMNs), 1 had an IPMN that progressed to invasive ductal adenocarcinoma, and 1 had pancreatic intraepithelial neoplasia. EUS and CT also diagnosed 3 patients with 5 extrapancreatic neoplasms. At EUS and ERCP abnormalities suggestive of chronic pancreatitis were more common in high-risk patients than in control subjects.\nCONCLUSIONS: Screening EUS and CT diagnosed significant asymptomatic pancreatic and extrapancreatic neoplasms in high-risk individuals. IPMN should be considered a part of the phenotype of familial pancreatic cancer. Abnormalities suggestive of chronic pancreatitis are identified more commonly at EUS and ERCP in high-risk individuals.","DOI":"10.1016/j.cgh.2006.02.005","ISSN":"1542-3565","note":"PMID: 16682259","title-short":"Screening for early pancreatic neoplasia in high-risk individuals","journalAbbreviation":"Clin. Gastroenterol. Hepatol.","language":"eng","author":[{"family":"Canto","given":"Marcia Irene"},{"family":"Goggins","given":"Michael"},{"family":"Hruban","given":"Ralph H."},{"family":"Petersen","given":"Gloria M."},{"family":"Giardiello","given":"Francis M."},{"family":"Yeo","given":"Charles"},{"family":"Fishman","given":"Elliott K."},{"family":"Brune","given":"Kieran"},{"family":"Axilbund","given":"Jennifer"},{"family":"Griffin","given":"Constance"},{"family":"Ali","given":"Syed"},{"family":"Richman","given":"Jeffrey"},{"family":"Jagannath","given":"Sanjay"},{"family":"Kantsevoy","given":"Sergey V."},{"family":"Kalloo","given":"Anthony N."}],"issued":{"date-parts":[["2006",6]]}}}],"schema":""} [17,23]. Furthermore, the prognosis in another group at risk of PC (patients with IPMN) was poorer in patients who stopped surveillance after 5 years of surveillance, which advocates for prolonged surveillance ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"hEFqnlKZ","properties":{"formattedCitation":"\\super [35]\\nosupersub{}","plainCitation":"[35]","noteIndex":0},"citationItems":[{"id":"BbVydael/3dMj1ZA9","uris":[""],"uri":[""],"itemData":{"id":34,"type":"article-journal","title":"Validation of the American Gastroenterological Association guidelines on management of intraductal papillary mucinous neoplasms: more than 5?years of follow-up","container-title":"European Radiology","page":"170-178","volume":"28","issue":"1","source":"PubMed","abstract":"OBJECTIVES: Recent guidelines suggest that imaging surveillance be conducted for 5?years for patients with at most one high-risk feature. If there were no significant changes, surveillance is stopped. We sought to validate this follow-up strategy.\nMETHODS: In study 1, data were analysed for 392 patients with intraductal papillary mucinous neoplasms (IPMNs) and at most one high-risk feature who were periodically followed up for more than 1?year with imaging tests. In study 2, data were analysed for 159 IPMN patients without worsening high-risk features after 5?years (stop surveillance group).\nRESULTS: In study 1, pancreatic cancer (PC) was identified in 12 patients (27.3%) in the endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) indication group and none in the non-EUS-FNA indication group (P?<?0.01). In the EUS-FNA indication group, 11 patients (25%) died, whereas 29 (8.3%) died in the non EUS-FNA indication group (P?<?0.01). In study 2 (stop surveillance group), PC was identified in three patients (1.9%) at 84, 103 and 145?months.\nCONCLUSIONS: PC risk and mortality for IPMNs not showing significant change for 5?years is likely to be low, and the non-EUS-FNA indication can provide reasonable decisions. However, three patients without worsening high-risk features for 5?years developed PC. The stop surveillance strategy should be reconsidered.\nKEY POINTS: ? The AGA guidelines provide reasonable clinical decisions for the EUS-FNA indication. ? In stop surveillance group, PC was identified in 3 patients (1.9%). ? In stop surveillance group, 2 of 3 PC patients died from PC. ? Risk of pancreatic cancer in \"stop surveillance\" group is not negligible.","DOI":"10.1007/s00330-017-4966-x","ISSN":"1432-1084","note":"PMID: 28770404","title-short":"Validation of the American Gastroenterological Association guidelines on management of intraductal papillary mucinous neoplasms","journalAbbreviation":"Eur Radiol","language":"eng","author":[{"family":"Imbe","given":"Koh"},{"family":"Nagata","given":"Naoyoshi"},{"family":"Hisada","given":"Yuya"},{"family":"Takasaki","given":"Yusuke"},{"family":"Sekine","given":"Katsunori"},{"family":"Mishima","given":"Saori"},{"family":"Kawazoe","given":"Akihito"},{"family":"Tajima","given":"Tsuyoshi"},{"family":"Shimbo","given":"Takuro"},{"family":"Yanase","given":"Mikio"},{"family":"Akiyama","given":"Junichi"},{"family":"Fujimoto","given":"Kazuma"},{"family":"Uemura","given":"Naomi"}],"issued":{"date-parts":[["2018",1]]}}}],"schema":""} [35].Place of endoscopic ultrasound for pancreatic screening of high-risk individualsPancreatic lesions found in endoscopic ultrasoundEUS pancreatic screening may identify pancreatic abnormalities in 19% to 79% of HRI ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"KNOTV23K","properties":{"formattedCitation":"(13\\uc0\\u8211{}16,25,31,34,35,37\\uc0\\u8211{}40)","plainCitation":"(13–16,25,31,34,35,37–40)","dontUpdate":true,"noteIndex":0},"citationItems":[{"id":"BbVydael/1nFkaaQF","uris":[""],"uri":[""],"itemData":{"id":50,"type":"article-journal","title":"The yield of first-time endoscopic ultrasonography in screening individuals at a high risk of developing pancreatic cancer","container-title":"The American Journal of Gastroenterology","page":"2175-2181","volume":"104","issue":"9","source":"PubMed","abstract":"OBJECTIVES: Approximately 10-15% of all pancreatic cancers (PCs) may be hereditary in origin. We investigated the use of endoscopic ultrasonography (EUS) for the screening of individuals at high risk for developing PC. In this paper the results of first-time screening with EUS are presented.\nMETHODS: Those eligible for screening in this study were first-degree family members of affected individuals from familial pancreatic cancer (FPC) families, mutation carriers of PC-prone hereditary syndromes, individuals with Peutz-Jeghers syndrome, and mutation carriers of other PC-prone hereditary syndromes with clustering (> or =2 cases per family) of PC. All individuals were asymptomatic and had not undergone EUS before.\nRESULTS: Forty-four individuals (M/F 18/26), aged 32-75 years underwent screening with EUS. Thirteen were from families with familial atypical multiple-mole melanoma (FAMMM), 21 with FPC, 3 individuals were diagnosed with hereditary pancreatitis, 2 were Peutz-Jeghers patients, 3 were BRCA1 and 2 were BRCA2 mutation carriers with familial clustering of PC, and 1 individual had a p53 mutation. Three (6.8%) patients had an asymptomatic mass lesion (12, 27, and 50 mm) in the body (n=2) or tail of the pancreas. All lesions were completely resected. Pathology showed moderately differentiated adenocarcinomas with N1 disease in the two patients with the largest lesions. EUS showed branch-type intraductal papillary mucinous neoplasia (IPMN) in seven individuals.\nCONCLUSIONS: Screening of individuals at a high risk for PC with EUS is feasible and safe. The incidence of clinically relevant findings at first screening is high with asymptomatic cancer in 7% and premalignant IPMN-like lesions in 16% in our series. Whether screening improves survival remains to be determined, as does the optimal screening interval with EUS.","DOI":"10.1038/ajg.2009.276","ISSN":"1572-0241","note":"PMID: 19491823","journalAbbreviation":"Am. J. Gastroenterol.","language":"eng","author":[{"family":"Poley","given":"J. W."},{"family":"Kluijt","given":"I."},{"family":"Gouma","given":"D. J."},{"family":"Harinck","given":"F."},{"family":"Wagner","given":"A."},{"family":"Aalfs","given":"C."},{"family":"Eijck","given":"C. H. J.","non-dropping-particle":"van"},{"family":"Cats","given":"A."},{"family":"Kuipers","given":"E. J."},{"family":"Nio","given":"Y."},{"family":"Fockens","given":"P."},{"family":"Bruno","given":"M. J."}],"issued":{"date-parts":[["2009",9]]}}},{"id":"BbVydael/L7ID64fl","uris":[""],"uri":[""],"itemData":{"id":61,"type":"article-journal","title":"Promising outcomes of screening for pancreatic cancer by genetic testing and endoscopic ultrasound","container-title":"Pancreas","page":"458-461","volume":"43","issue":"3","source":"PubMed","abstract":"OBJECTIVE: This study aimed to determine if screening patients based on certain cancer syndromes or family history criteria can lead to early detection of pancreatic cancer.\nMETHODS: This was a cohort study from 2008 to 2011 at a large tertiary referral center. A total of 30 patients met high-risk criteria after genetic counseling and were referred to a gastroenterologist for possible endoscopic ultrasound (EUS).\nRESULTS: Of the 30 patients, 16 underwent EUS. Subsequently, 3 patients had fine needle aspiration. Two patients had pancreatic adenocarcinoma, and 1 patient had an intraductal papillary mucinous neoplasm with low-grade dysplasia. The 2 patients with pancreatic adenocarcinoma both had breast cancer and BRCA2 mutations. The patient with the intraductal papillary mucinous neoplasm had Peutz-Jeghers syndrome. All 3 patients underwent surgery and have remained cancer free.\nCONCLUSIONS: Genetic risk assessment with EUS +/- fine needle aspiration in high-risk patients may lead to earlier detection of pancreatic cancer and potentially improve overall morbidity and mortality. Greater emphasis should be placed on screening patients for hereditary cancer syndromes that increase the risk of pancreatic cancer.","DOI":"10.1097/MPA.0000000000000052","ISSN":"1536-4828","note":"PMID: 24622079","journalAbbreviation":"Pancreas","language":"eng","author":[{"family":"Sud","given":"Anchal"},{"family":"Wham","given":"Deborah"},{"family":"Catalano","given":"Marc"},{"family":"Guda","given":"Nalini M."}],"issued":{"date-parts":[["2014",4]]}}},{"id":"BbVydael/TT8LQAKI","uris":[""],"uri":[""],"itemData":{"id":79,"type":"article-journal","title":"Five years of prospective screening of high-risk individuals from families with familial pancreatic cancer","container-title":"Gut","page":"1410-1418","volume":"58","issue":"10","source":"PubMed","abstract":"OBJECTIVE: Familial pancreatic cancer (FPC) accounts for approximately 3% of all pancreatic cancer (PC) cases. It has been suggested that high-risk individuals (HRIs) should be offered a screening programme.\nAIM: To evaluate the diagnostic yield of a prospective screening programme in HRIs from families with FPC over a period of 5 years.\nMETHODS: HRIs of families with FPC of the National German Familial Pancreatic Cancer Registry (FaPaCa) were counselled and enrolled in a prospective, board-approved PC screening programme. Screening included clinical examination, laboratory tests, endoscopic ultrasound (EUS) and MRI with magnetic resonance cholangiopancreaticography (MRCP) and MR angiography.\nRESULTS: Between June 2002 and December 2007, 76 HRIs of families with FPC took part in the screening programme with a total of 182 examination visits. Twenty-eight patients revealed abnormalities in EUS (n = 25) and/or MR/MRCP (n = 12). In 7 patients fine needle aspiration cytology was performed. Operative pancreatic explorations were performed in 7 individuals, resulting in limited resections in 6 cases. Histopathological examination of the resected specimens showed serous oligocystic adenomas (n = 3), pancreatic intraepithelial neoplasia 1 (PanIN1) lesions with lobular fibrosis (n = 1), PanIN2 lesions (n = 1) and PanIN1 lesion plus a gastric type intraductal papillary mucinous neoplasm (IPMN) (n = 1).\nCONCLUSIONS: In FPC an EUS/MR/MRCP-based screening programme leads to the detection of potential precursor lesions of PC. However, the yield of an extensive screening programme is low, especially since the tumourigenic value of low grade PanIN lesions is not yet defined. Taking into account the enormous psychological stress for the tested individual and the high costs, a general PC screening in HRIs is not justified.","DOI":"10.1136/gut.2008.171611","ISSN":"1468-3288","note":"PMID: 19470496","journalAbbreviation":"Gut","language":"eng","author":[{"family":"Langer","given":"P."},{"family":"Kann","given":"P. H."},{"family":"Fendrich","given":"V."},{"family":"Habbe","given":"N."},{"family":"Schneider","given":"M."},{"family":"Sina","given":"M."},{"family":"Slater","given":"E. P."},{"family":"Heverhagen","given":"J. T."},{"family":"Gress","given":"T. M."},{"family":"Rothmund","given":"M."},{"family":"Bartsch","given":"D. K."}],"issued":{"date-parts":[["2009",10]]}}},{"id":"BbVydael/9sdQOJDj","uris":[""],"uri":[""],"itemData":{"id":88,"type":"article-journal","title":"Screening for pancreatic cancer in a high-risk population with serum CA 19-9 and targeted EUS: a feasibility study","container-title":"Gastrointestinal Endoscopy","page":"87-95","volume":"74","issue":"1","source":"PubMed","abstract":"BACKGROUND: Earlier detection of pancreatic adenocarcinoma is needed.\nOBJECTIVE: To determine whether early pancreatic neoplasia can be detected in a high-risk population by using CA 19-9 followed by targeted EUS.\nDESIGN: Prospective cohort study.\nSETTING: Two academic medical centers.\nPATIENTS: Eligible patients met age criteria and had at least 1 first-degree relative with pancreatic adenocarcinoma.\nINTERVENTIONS: A serum CA 19-9 was performed on all patients. EUS was performed if the CA 19-9 level was elevated. FNA of identified lesions was performed. Patients with pancreatic cancer detected by using this screening protocol were compared with patients presenting off-protocol for staging data. Medicare reimbursement rates were used to derive cost data.\nMAIN OUTCOME MEASUREMENTS: Detection of early pancreatic neoplasia.\nRESULTS: A total of 546 patients were enrolled. CA 19-9 was elevated in 27 patients (4.9%, 95% CI, 3.2%-7.1%). Neoplastic or malignant findings were detected in 5 patients (0.9%, 95% CI, 0.3%-2.1%), and pancreatic adenocarcinoma in 1 patient (0.2%, 95% CI, 0.005%-1.02%). The patient with pancreatic cancer detected as part of this protocol was 1 of 2 patients presenting to the University of Vermont with stage 1 cancer. The cost to detect 1 pancreatic neoplasia was $8431. The cost to detect 1 pancreatic adenocarcinoma was $41,133.\nLIMITATIONS: The sample size is adequate only to demonstrate the feasibility of this approach.\nCONCLUSIONS: Potentially curative pancreatic adenocarcinoma can be identified with this screening protocol. Stage 1 pancreatic cancer is more likely to be detected by using this screening protocol than by using standard means of detection.","DOI":"10.1016/j.gie.2011.03.1235","ISSN":"1097-6779","note":"PMID: 21704809","title-short":"Screening for pancreatic cancer in a high-risk population with serum CA 19-9 and targeted EUS","journalAbbreviation":"Gastrointest. Endosc.","language":"eng","author":[{"family":"Zubarik","given":"Richard"},{"family":"Gordon","given":"Stuart R."},{"family":"Lidofsky","given":"Steven D."},{"family":"Anderson","given":"Scott R."},{"family":"Pipas","given":"J. Marc"},{"family":"Badger","given":"Gary"},{"family":"Ganguly","given":"Eric"},{"family":"Vecchio","given":"James"}],"issued":{"date-parts":[["2011",7]]}}},{"id":"BbVydael/sxr8Ecxk","uris":[""],"uri":[""],"itemData":{"id":58,"type":"article-journal","title":"Frequent detection of pancreatic lesions in asymptomatic high-risk individuals","container-title":"Gastroenterology","page":"796-804; quiz e14-15","volume":"142","issue":"4","source":"PubMed","abstract":"BACKGROUND & AIMS: The risk of pancreatic cancer is increased in patients with a strong family history of pancreatic cancer or a predisposing germline mutation. Screening can detect curable, noninvasive pancreatic neoplasms, but the optimal imaging approach is not known. We determined the baseline prevalence and characteristics of pancreatic abnormalities using 3 imaging tests to screen asymptomatic, high-risk individuals (HRIs).\nMETHODS: We screened 225 asymptomatic adult HRIs at 5 academic US medical centers once, using computed tomography (CT), magnetic resonance imaging (MRI), and endoscopic ultrasonography (EUS). We compared results in a blinded, independent fashion.\nRESULTS: Ninety-two of 216 HRIs (42%) were found to have at least 1 pancreatic mass (84 cystic, 3 solid) or a dilated pancreatic duct (n = 5) by any of the imaging modalities. Fifty-one of the 84 HRIs with a cyst (60.7%) had multiple lesions, typically small (mean, 0.55 cm; range, 2-39 mm), in multiple locations. The prevalence of pancreatic lesions increased with age; they were detected in 14% of subjects younger than 50 years old, 34% of subjects 50-59 years old, and 53% of subjects 60-69 years old (P < .0001). CT, MRI, and EUS detected a pancreatic abnormality in 11%, 33.3%, and 42.6% of the HRIs, respectively. Among these abnormalities, proven or suspected neoplasms were identified in 85 HRIs (82 intraductal papillary mucinous neoplasms and 3 pancreatic endocrine tumors). Three of 5 HRIs who underwent pancreatic resection had high-grade dysplasia in less than 3 cm intraductal papillary mucinous neoplasms and in multiple intraepithelial neoplasias.\nCONCLUSIONS: Screening of asymptomatic HRIs frequently detects small pancreatic cysts, including curable, noninvasive high-grade neoplasms. EUS and MRI detect pancreatic lesions better than CT.","DOI":"10.1053/j.gastro.2012.01.005","ISSN":"1528-0012","note":"PMID: 22245846\nPMCID: PMC3321068","journalAbbreviation":"Gastroenterology","language":"eng","author":[{"family":"Canto","given":"Marcia Irene"},{"family":"Hruban","given":"Ralph H."},{"family":"Fishman","given":"Elliot K."},{"family":"Kamel","given":"Ihab R."},{"family":"Schulick","given":"Richard"},{"family":"Zhang","given":"Zhe"},{"family":"Topazian","given":"Mark"},{"family":"Takahashi","given":"Naoki"},{"family":"Fletcher","given":"Joel"},{"family":"Petersen","given":"Gloria"},{"family":"Klein","given":"Alison P."},{"family":"Axilbund","given":"Jennifer"},{"family":"Griffin","given":"Constance"},{"family":"Syngal","given":"Sapna"},{"family":"Saltzman","given":"John R."},{"family":"Mortele","given":"Koenraad J."},{"family":"Lee","given":"Jeffrey"},{"family":"Tamm","given":"Eric"},{"family":"Vikram","given":"Raghunandan"},{"family":"Bhosale","given":"Priya"},{"family":"Margolis","given":"Daniel"},{"family":"Farrell","given":"James"},{"family":"Goggins","given":"Michael"},{"literal":"American Cancer of the Pancreas Screening (CAPS) Consortium"}],"issued":{"date-parts":[["2012",4]]}}},{"id":"BbVydael/NFPiCpG1","uris":[""],"uri":[""],"itemData":{"id":46,"type":"article-journal","title":"Screening for early pancreatic neoplasia in high-risk individuals: a prospective controlled study","container-title":"Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association","page":"766-781; quiz 665","volume":"4","issue":"6","source":"PubMed","abstract":"BACKGROUND & AIMS: Individuals with a strong family history of pancreatic cancer and persons with Peutz-Jeghers syndrome (PJS) have an increased risk for pancreatic cancer. This study screened for early pancreatic neoplasia and compared the pancreatic abnormalities in high-risk individuals and control subjects.\nMETHODS: High-risk individuals with PJS or a strong family history of pancreatic cancer were prospectively evaluated with baseline and 12-month computed tomography (CT) scan and endoscopic ultrasonography (EUS). If EUS was abnormal, EUS-fine-needle aspiration and endoscopic retrograde cholangiopancreatography (ERCP) were performed. Surgery was offered to patients with potentially neoplastic lesions. Radiologic findings and pathologic diagnoses were compared. Patients undergoing EUS and/or ERCP for benign non-pancreatic indications were concurrently enrolled as control subjects.\nRESULTS: Seventy-eight high-risk patients (72 from familial pancreatic cancer kindreds, 6 PJS) and 149 control patients were studied. To date, 8 patients with pancreatic neoplasia have been confirmed by surgery or fine-needle aspiration (10% yield of screening); 6 patients had 8 benign intraductal papillary mucinous neoplasms (IPMNs), 1 had an IPMN that progressed to invasive ductal adenocarcinoma, and 1 had pancreatic intraepithelial neoplasia. EUS and CT also diagnosed 3 patients with 5 extrapancreatic neoplasms. At EUS and ERCP abnormalities suggestive of chronic pancreatitis were more common in high-risk patients than in control subjects.\nCONCLUSIONS: Screening EUS and CT diagnosed significant asymptomatic pancreatic and extrapancreatic neoplasms in high-risk individuals. IPMN should be considered a part of the phenotype of familial pancreatic cancer. Abnormalities suggestive of chronic pancreatitis are identified more commonly at EUS and ERCP in high-risk individuals.","DOI":"10.1016/j.cgh.2006.02.005","ISSN":"1542-3565","note":"PMID: 16682259","title-short":"Screening for early pancreatic neoplasia in high-risk individuals","journalAbbreviation":"Clin. Gastroenterol. Hepatol.","language":"eng","author":[{"family":"Canto","given":"Marcia Irene"},{"family":"Goggins","given":"Michael"},{"family":"Hruban","given":"Ralph H."},{"family":"Petersen","given":"Gloria M."},{"family":"Giardiello","given":"Francis M."},{"family":"Yeo","given":"Charles"},{"family":"Fishman","given":"Elliott K."},{"family":"Brune","given":"Kieran"},{"family":"Axilbund","given":"Jennifer"},{"family":"Griffin","given":"Constance"},{"family":"Ali","given":"Syed"},{"family":"Richman","given":"Jeffrey"},{"family":"Jagannath","given":"Sanjay"},{"family":"Kantsevoy","given":"Sergey V."},{"family":"Kalloo","given":"Anthony N."}],"issued":{"date-parts":[["2006",6]]}}},{"id":"BbVydael/ujvJfaIr","uris":[""],"uri":[""],"itemData":{"id":52,"type":"article-journal","title":"Pancreatic cancer screening in a prospective cohort of high-risk patients: a comprehensive strategy of imaging and genetics","container-title":"Clinical Cancer Research: An Official Journal of the American Association for Cancer Research","page":"5028-5037","volume":"16","issue":"20","source":"PubMed","abstract":"PURPOSE: Pancreatic cancer is a virtually uniformly fatal disease. We aimed to determine if screening to identify curable neoplasms is effective when offered to patients at high risk.\nEXPERIMENTAL DESIGN: Patients at high risk of pancreatic cancer were prospectively enrolled into a screening program. Endoscopic ultrasound (EUS), magnetic resonance imaging (MRI), and genetic testing were offered by a multidisciplinary team according to each patient's risk.\nRESULTS: Fifty-one patients in 43 families were enrolled, with mean age of 52 years, 35% of whom were male. Of these patients, 31 underwent EUS and 33 MRI. EUS revealed two patients with pancreatic cancer (one resectable, one metastatic), five with intraductal papillary mucinous neoplasms (IPMN), seven with cysts, and six with parenchymal changes. Five had pancreatic surgery (one total pancreatectomy for pancreatic cancer, three distal and one central pancreatectomy for pancreatic intraepithelial neoplasia 2 and IPMN). A total of 24 (47%) had genetic testing (19 for BRCA1/2 mutations, 4 for CDKN2A, 1 for MLH1/MSH2) and 7 were positive for BRCA1/2 mutations. Four extrapancreatic neoplasms were found: two ovarian cancers on prophylactic total abdominal hysterectomy and bilateral salpingo-oophorectomy, one carcinoid, and one papillary thyroid carcinoma. Overall, 6 (12%) of the 51 patients had neoplastic lesions in the pancreas and 9 (18%) had neoplasms in any location. All were on the initial round of screening. All patients remain alive and without complications of screening.\nCONCLUSIONS: Pancreatic cancer screening for high-risk patients with a comprehensive strategy of imaging and genetics is effective and identifies curable neoplasms that can be resected. Ongoing study will better define who will benefit from screening and what screening strategy will be the most effective.","DOI":"10.1158/1078-R-09-3209","ISSN":"1078-0432","note":"PMID: 20876795","title-short":"Pancreatic cancer screening in a prospective cohort of high-risk patients","journalAbbreviation":"Clin. Cancer Res.","language":"eng","author":[{"family":"Verna","given":"Elizabeth C."},{"family":"Hwang","given":"Caroline"},{"family":"Stevens","given":"Peter D."},{"family":"Rotterdam","given":"Heidrun"},{"family":"Stavropoulos","given":"Stavros N."},{"family":"Sy","given":"Carolyn D."},{"family":"Prince","given":"Martin A."},{"family":"Chung","given":"Wendy K."},{"family":"Fine","given":"Robert L."},{"family":"Chabot","given":"John A."},{"family":"Frucht","given":"Harold"}],"issued":{"date-parts":[["2010",10,15]]}}},{"id":"BbVydael/bbEwgRsE","uris":[""],"uri":[""],"itemData":{"id":67,"type":"article-journal","title":"Feasibility and yield of screening in relatives from familial pancreatic cancer families","container-title":"The American Journal of Gastroenterology","page":"946-954","volume":"106","issue":"5","source":"PubMed","abstract":"OBJECTIVES: Pancreatic adenocarcinoma is a lethal disease. Over 80% of patients are found to have metastatic disease at the time of diagnosis. Strategies to improve disease-specific outcome include identification and early detection of precursor lesions or early cancers in high-risk groups. In this study, we investigate whether screening at-risk relatives of familial pancreatic cancer (FPC) patients is safe and has significant yield.\nMETHODS: We enrolled 309 asymptomatic at-risk relatives into our Familial Pancreatic Tumor Registry (FPTR) and offered them screening with magnetic resonance cholangiopancreaticogram (MRCP) followed by endoscopic ultrasound (EUS) with fine needle aspiration if indicated. Relatives with findings were referred for surgical evaluation.\nRESULTS: As of 1 August 2009, 109 relatives had completed at least one cycle of screening. Abnormal radiographic findings were present on initial screening in 18/109 patients (16.5%), 15 of whom underwent EUS. A significant abnormality was confirmed in 9 of 15 patients, 6 of whom ultimately had surgery for an overall diagnostic yield of 8.3% (9/109). Yield was greatest in relatives >65 years old (35%, 6/17) when compared with relatives 55-65 years (3%, 1/31) and relatives <55 years (3%, 2/61).\nCONCLUSIONS: Screening at-risk relatives from FPC families has a significant diagnostic yield, particularly in relatives >65 years of age, confirming prior studies. MRCP as initial screening modality is safe and effective.","DOI":"10.1038/ajg.2011.65","ISSN":"1572-0241","note":"PMID: 21468009\nPMCID: PMC3683863","journalAbbreviation":"Am. J. Gastroenterol.","language":"eng","author":[{"family":"Ludwig","given":"Emmy"},{"family":"Olson","given":"Sara H."},{"family":"Bayuga","given":"Sharon"},{"family":"Simon","given":"Jennifer"},{"family":"Schattner","given":"Mark A."},{"family":"Gerdes","given":"Hans"},{"family":"Allen","given":"Peter J."},{"family":"Jarnagin","given":"William R."},{"family":"Kurtz","given":"Robert C."}],"issued":{"date-parts":[["2011",5]]}}},{"id":"BbVydael/0zDhQJOq","uris":[""],"uri":[""],"itemData":{"id":107,"type":"article-journal","title":"Endoscopic Ultrasound-Based Pancreatic Cancer Screening of High-Risk Individuals: A Prospective Observational Trial","container-title":"Pancreas","page":"586-591","volume":"47","issue":"5","source":"PubMed","abstract":"OBJECTIVES: Pancreatic cancer (PC), a common cause of cancer death, is rarely diagnosed at an early stage. Early detection of PC may improve outcomes in affected patients. This study evaluated the utility of screening of high-risk individuals (HRIs) using an endoscopic ultrasound (EUS)-only approach to detect early malignant changes.\nMETHODS: A prospective PC screening program for HRIs was opened in 2007. Fifty-eight patients have enrolled to date. Patients with normal EUS examinations underwent repeat EUS annually for 5 years. Patients with abnormal EUS underwent fine-needle aspiration (FNA) if a mass/cyst 1 cm or longer was found. Those with cysts/mass shorter than 1 cm or benign FNA underwent repeat EUS in 3 months. If unchanged, patients were followed with magnetic resonance imaging.\nRESULTS: Thirty-nine patients (67%) had initial normal EUS examinations, and 16 patients completed the 5-year trial. Five patients who initially had a normal EUS developed cysts on subsequent examinations. Of the 24 subjects (41%) with abnormal findings, 3 underwent FNA: 2 consistent with intraductal papillary mucinous neoplasm, 1 with benign cytology. The 21 remaining patients had 1 subcentimeter cyst or more followed by magnetic resonance imaging. No PCs have been detected.\nCONCLUSIONS: Precancerous cysts are frequently detected with EUS in HRI. Whether screening impacts survival in HRIs remains unclear and requires further evaluation in larger multicenter trials.","DOI":"10.1097/MPA.0000000000001038","ISSN":"1536-4828","note":"PMID: 29683970","title-short":"Endoscopic Ultrasound-Based Pancreatic Cancer Screening of High-Risk Individuals","journalAbbreviation":"Pancreas","language":"eng","author":[{"family":"Gangi","given":"Alexandra"},{"family":"Malafa","given":"Mokenge"},{"family":"Klapman","given":"Jason"}],"issued":{"date-parts":[["2018",6]]}}},{"id":"BbVydael/jbhwOW3r","uris":[""],"uri":[""],"itemData":{"id":188,"type":"article-journal","title":"Early diagnosis and treatment of pancreatic dysplasia in patients with a family history of pancreatic cancer","container-title":"Annals of Internal Medicine","page":"247-255","volume":"131","issue":"4","source":"PubMed","abstract":"BACKGROUND: Pancreatic cancer, the fourth most common cause of cancer death in the United States, is hereditary in an estimated 10% of cases. Surveillance of patients with a familial predisposition for pancreatic cancer has not been systematically evaluated.\nOBJECTIVE: To develop a surveillance program that can identify and treat patients who have precancerous conditions of the pancreas and a family history of pancreatic cancer.\nDESIGN: Prospective cohort study.\nSETTING: University medical center.\nPATIENTS: 14 patients from three kindreds with a history of pancreatic cancer.\nINTERVENTIONS: Endoscopic ultrasonography, endoscopic retrograde cholangiopancreatography (ERCP), spiral computed tomography, and serum carcinoembryonic antigen and CA19-9 analysis were performed in all patients. Four affected patients were tested for the K-ras mutation.\nMAIN OUTCOME MEASUREMENT: Pancreatic dysplasia was determined by histologic evaluation.\nRESULTS: Seven of the 14 patients were believed to have dysplasia on the basis of clinical history and abnormalities on endoscopic ultrasonography and ERCP and were referred for pancreatectomy. All 7 patients had histologic evidence of dysplasia in pancreatectomy specimens. Findings on endoscopic ultrasonography were subtle, nonspecific, and similar to those seen in patients with chronic pancreatitis. Findings on ERCP ranged from mild and focal side-branch duct irregularities and small sacculations to main-duct strictures and grapelike clusters of saccules. Some of these changes are typical of chronic pancreatitis, but others are more distinctive. Spiral computed tomography and serum tumor markers had low sensitivity in the detection of pancreatic dysplasia. Analysis for the K-ras mutation yielded positive results in 3 of 4 patients with dysplasia.\nCONCLUSIONS: Thorough screening of patients with a family history of pancreatic cancer is feasible. Clinical data combined with imaging studies (endoscopic ultrasonography and ERCP) can be used to identify high-risk patients who have dysplasia. The role of molecular genetic testing is uncertain at this time.","ISSN":"0003-4819","note":"PMID: 10454945","journalAbbreviation":"Ann. Intern. Med.","language":"eng","author":[{"family":"Brentnall","given":"T. A."},{"family":"Bronner","given":"M. P."},{"family":"Byrd","given":"D. R."},{"family":"Haggitt","given":"R. C."},{"family":"Kimmey","given":"M. B."}],"issued":{"date-parts":[["1999",8,17]]}}},{"id":"BbVydael/A1bcnT9r","uris":[""],"uri":[""],"itemData":{"id":84,"type":"article-journal","title":"Cost-effectiveness of pancreatic cancer screening in familial pancreatic cancer kindreds","container-title":"Gastrointestinal Endoscopy","page":"23-29","volume":"57","issue":"1","source":"PubMed","abstract":"BACKGROUND: Endoscopic screening of families predisposed to pancreatic cancer is increasingly used, but the cost-effectiveness of screening is unknown.\nMETHODS: A decision analysis was used to compare one-time screening for pancreatic dysplasia with EUS to no screening in a hypothetical cohort of 100 members of familial pancreatic cancer kindreds. Abnormal EUS findings are confirmed with ERCP and patients with abnormal findings are candidates for total pancreatectomy. Lifetime medical care costs and life expectancy were modeled, and the main analysis was conducted from the third-party payer perspective. The base-case analysis assumed a 20% prevalence of pancreatic dysplasia and 90% sensitivity of EUS and ERCP.\nRESULTS: Endoscopic screening was cost-effective, with an incremental cost-effectiveness ratio of $16,885/life-year saved. Screening was more cost-effective as the probability of dysplasia increased and as the sensitivity of EUS and ERCP increased. Screening remained cost-effective if the prevalence of dysplasia was greater than 16% or if the sensitivity of EUS was greater than 84%. Procedure costs had a limited impact on cost-effectiveness.\nCONCLUSIONS: Endoscopic screening of carefully selected members of familial pancreatic cancer kindreds appears to increase patient life expectancy in a cost-effective manner. Screening should be performed in centers that have experience with endoscopic screening for pancreatic dysplasia. The cost-effectiveness of repeated screening remains to be determined.","DOI":"10.1067/mge.2003.28","ISSN":"0016-5107","note":"PMID: 12518126","journalAbbreviation":"Gastrointest. Endosc.","language":"eng","author":[{"family":"Rulyak","given":"Stephen J."},{"family":"Kimmey","given":"Michael B."},{"family":"Veenstra","given":"David L."},{"family":"Brentnall","given":"Teresa A."}],"issued":{"date-parts":[["2003",1]]}}},{"id":"BbVydael/uPpbB5zq","uris":[""],"uri":[""],"itemData":{"id":192,"type":"article-journal","title":"Pancreatic cancer screening in high-risk individuals with germline genetic mutations","container-title":"Gastrointestinal Endoscopy","page":"1443-1450","volume":"87","issue":"6","source":"PubMed","abstract":"BACKGROUND AND AIMS: Pancreatic cancer (PC) is a deadly disease that is most commonly diagnosed at an incurable stage. Different high-risk genetic variants and cancer syndromes increase the lifetime risk of developing PC. This study aims to assess the yield of initial PC screening in patients with high-risk germline mutations.\nMETHODS: Asymptomatic adults underwent PC screening by EUS, magnetic resonance imaging, or CT during a 10-year period and were retrospectively identified. High-risk individuals were defined as carrying germline mutations in BRCA1, BRCA2, p53 (Li-Fraumeni), STK11 (Peutz-Jeghers), MSH2 (Lynch), ATM (ataxia-telangiectasia), or APC (familial adenomatous polyposis). Patients without germline mutations were excluded.\nRESULTS: In total, 86 patients met the study criteria. The median age was 48.5 years (interquartile range, 40-58), 79.1% (68) were women, and 43.0% (37) had a family history of PC. The genetic mutations were BRCA2 (50,?58.1%), BRCA1 (14, 16.3%), p53 (12, 14.0%), STK11 (5, 5.8%), MSH2 (3, 3.5%), ATM (1, 1.2%), and APC (1,?1.2%). Screening detected a pancreatic abnormality (PA) in 26.7% (23/86), including cysts (11, 47.8%), hyperechoic strands and foci (10, 43.5%), and mild pancreatic duct dilation (2, 8.7%). Patients older than 60 years were more likely to have a PA detected (P?= .043). EUS detected more PAs than magnetic resonance imaging or CT. No?cases of PC were diagnosed by screening or during follow-up (median, 29.8 months; interquartile range, 21.7-43.5).\nCONCLUSIONS: Unless indicated otherwise by family or personal history, PC screening under the age of 50 is low yield. Linear EUS may be the preferred modality for initial PC screening.","DOI":"10.1016/j.gie.2017.12.019","ISSN":"1097-6779","note":"PMID: 29309780","journalAbbreviation":"Gastrointest. Endosc.","language":"eng","author":[{"family":"DaVee","given":"Tomas"},{"family":"Coronel","given":"Emmanuel"},{"family":"Papafragkakis","given":"Charilaos"},{"family":"Thaiudom","given":"Sayam"},{"family":"Lanke","given":"Gandhi"},{"family":"Chakinala","given":"Raja C."},{"family":"Nogueras González","given":"Graciela M."},{"family":"Bhutani","given":"Manoop S."},{"family":"Ross","given":"William A."},{"family":"Weston","given":"Brian R."},{"family":"Lee","given":"Jeffrey H."}],"issued":{"date-parts":[["2018",6]]}}}],"schema":""} (13–16, 25, 31, 34, 35, 37–40) (Table 2). These pancreatic “abnormalities” include cystic lesions (13%-49%) (Figures 1 and 2), chronic pancreatitis-like parenchymal changes (14%-77%) (Figure 3) and solid lesions (0%-46%) (Figure 4), which are always considered suspicious ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"oyjIYYcc","properties":{"formattedCitation":"\\super [4,10,18,23,26,27,39,40]\\nosupersub{}","plainCitation":"[4,10,18,23,26,27,39,40]","noteIndex":0},"citationItems":[{"id":"BbVydael/zZTZnNXC","uris":[""],"uri":[""],"itemData":{"id":36,"type":"article-journal","title":"Refinement of screening for familial pancreatic cancer","container-title":"Gut","page":"1314-1321","volume":"65","issue":"8","source":"PubMed","abstract":"OBJECTIVE: Surveillance programmes are recommended for individuals at risk (IAR) of familial pancreatic cancer (FPC) to detect early pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC). However, the age to begin screening and the optimal screening protocol remain to be determined.\nMETHODS: IAR from non-CDKN2A FPC families underwent annual screening by MRI with endoscopic ultrasonography (EUS) in board-approved prospective screening programmes at three tertiary referral centres. The diagnostic yield according to age and different screening protocols was analysed.\nRESULTS: 253 IAR with a median age of 48 (25-81)?years underwent screening with a median of 3 (1-11) screening visits during a median follow-up of 28 (1-152)?months. 134 (53%) IAR revealed pancreatic lesions on imaging, mostly cystic (94%), on baseline or follow-up screening. Lesions were significantly more often identified in IAR above the age of 45?years (p<0.0001). In 21 IAR who underwent surgery, no significant lesions (PDAC, pancreatic intraepithelial neoplasia (PanIN) 3 lesions, high-grade intraductal papillary mucinous neoplasia (IPMN)) were detected before the age of 50?years. Potentially relevant lesions (multifocal PanIN2 lesions, low/moderate-grade branch-duct IPMNs) occurred also significantly more often after the age of 50?years (13 vs 2, p<0.0004). The diagnostic yield of potentially relevant lesions was not different between screening protocols using annual MRI with EUS (n=98) or annual MRI with EUS every 3rd year (n=198) and between IAR screened at intervals of 12?months (n=180) or IAR that decided to be screened at ≥24?months intervals (n=30).\nCONCLUSIONS: It appears safe to start screening for PDAC in IAR of non-CDKN2a FPC families at the age of 50?years. MRI-based screening supplemented by EUS at baseline and every 3rd year or when changes in MRI occur appears to be efficient.","DOI":"10.1136/gutjnl-2015-311098","ISSN":"1468-3288","note":"PMID: 27222532","journalAbbreviation":"Gut","language":"eng","author":[{"family":"Bartsch","given":"D. K."},{"family":"Slater","given":"E. P."},{"family":"Carrato","given":"A."},{"family":"Ibrahim","given":"I. S."},{"family":"Guillen-Ponce","given":"C."},{"family":"Vasen","given":"H. F. A."},{"family":"Matth?i","given":"E."},{"family":"Earl","given":"J."},{"family":"Jendryschek","given":"F. S."},{"family":"Figiel","given":"J."},{"family":"Steinkamp","given":"M."},{"family":"Ramaswamy","given":"A."},{"family":"Vázquez-Sequeiros","given":"E."},{"family":"Mu?oz-Beltran","given":"M."},{"family":"Montans","given":"J."},{"family":"Mocci","given":"E."},{"family":"Bonsing","given":"B. A."},{"family":"Wasser","given":"M."},{"family":"Kl?ppel","given":"G."},{"family":"Langer","given":"P."},{"family":"Fendrich","given":"V."},{"family":"Gress","given":"T. M."}],"issued":{"date-parts":[["2016"]]}}},{"id":"BbVydael/jiIYxhxp","uris":[""],"uri":[""],"itemData":{"id":65,"type":"article-journal","title":"PanGen-Fam: Spanish registry of hereditary pancreatic cancer","container-title":"European Journal of Cancer (Oxford, England: 1990)","page":"1911-1917","volume":"51","issue":"14","source":"PubMed","abstract":"PURPOSE: To describe the organisation of the registry and the preliminary results in terms of characteristics of high-risk pancreatic ductal adenocarcinoma (PDAC) families recruited to date and findings of the screening programme. To compare early onset sporadic cases (?50 years), sporadic cases (>50 years) and cases with family history of cancer, for PDAC possible risk factors.\nMETHODS/PATIENTS: Families with hereditary cancer syndromes predisposing to PDAC were recruited from two main sources: Spanish hospitals participating in PanGenEU, a pan-European multicentre case-control study, and their genetic counseling unit. Individuals at high-risk of PDAC were enrolled into a screening programme, consisting of Endoscopic ultrasound, computerised tomography, magnetic resonance imaging. Genetic testing of candidate genes was offered according to each patient's risk.\nRESULTS: Among 577 consecutive PDAC cases, recruited via PanGenEU, 36 (6%) had ?2 first-degree relative with PDAC: Familial pancreatic cancer (FPC). So far PanGen-Fam has recruited 42 high-risk PDAC families; 25 (60%) had FPC. Five index cases with cancer were positive for BRCA2 and one for BRCA1 germline mutations. In the second year of prospective PDAC screening, one neuroendocrine tumour and a high-grade dysplasia lesion suspicious of carcinoma were diagnosed among 41 high-risk individuals. Furthermore EUS detected chronic-pancreatitis-like parenchymal changes in 15 patients.\nCONCLUDING STATEMENT: The identification and recruitment of PDAC high-risk families into the PanGen-Fam registry provides an opportunity to detect early onset cancer and precursor pancreatic cancer lesions at a potentially curative stage and to increase the knowledge of the natural history of the disease.","DOI":"10.1016/j.ejca.2015.07.004","ISSN":"1879-0852","note":"PMID: 26212471","title-short":"PanGen-Fam","journalAbbreviation":"Eur. J. Cancer","language":"eng","author":[{"family":"Mocci","given":"E."},{"family":"Guillen-Ponce","given":"C."},{"family":"Earl","given":"J."},{"family":"Marquez","given":"M."},{"family":"Solera","given":"J."},{"family":"Salazar-López","given":"M.-T."},{"family":"Calcedo-Arnáiz","given":"C."},{"family":"Vázquez-Sequeiros","given":"E."},{"family":"Montans","given":"J."},{"family":"Mu?oz-Beltrán","given":"M."},{"family":"Vicente-Bártulos","given":"A."},{"family":"González-Gordaliza","given":"C."},{"family":"Sanjuanbenito","given":"A."},{"family":"Guerrero","given":"C."},{"family":"Mendía","given":"E."},{"family":"Lisa","given":"E."},{"family":"Lobo","given":"E."},{"family":"Martínez","given":"J. C."},{"family":"Real","given":"F. X."},{"family":"Malats","given":"N."},{"family":"Carrato","given":"A."}],"issued":{"date-parts":[["2015",9]]}}},{"id":"BbVydael/C3zHNTfr","uris":[""],"uri":[""],"itemData":{"id":95,"type":"article-journal","title":"Results of surveillance in individuals at high-risk of pancreatic cancer: A systematic review and meta-analysis","container-title":"United European Gastroenterology Journal","page":"489-499","volume":"6","issue":"4","source":"PubMed","abstract":"Background: Data on surveillance for pancreatic ductal adenocarcinoma (PDAC) in high-risk individuals (HRIs) with \"familial pancreatic cancer\" (FPC) and specific syndromes are limited and heterogeneous.\nObjective: We conducted a systematic review and meta-analysis of PDAC surveillance studies in HRIs.\nMethods: Prevalence of solid/cystic pancreatic lesions and of lesions considered a successful target of surveillance (proven resectable PDAC and high-grade precursors) was pooled across studies. The rate of lesions diagnosed by endoscopic ultrasonography (EUS)/magnetic resonance imaging (MRI) and across different HRI groups was calculated.\nResults: Sixteen studies incorporating 1588 HRIs were included. The pooled prevalence of pancreatic solid and cystic lesions was 5.8% and 20.2%, respectively. The pooled prevalence of patients with lesions considered a successful target of surveillance was 3.3%, being similar to EUS or MRI and varying across subgroups, being 3% in FPC, 4% in hereditary pancreatitis, 5% in familial melanoma, 6.3% in hereditary breast/ovarian cancer, and 12.2% in Peutz-Jeghers syndrome. The pooled estimated rate of lesions considered a successful target of surveillance during follow-up was 5/1000 person-years.\nConclusion: Surveillance programs identify successful target lesions in 3.3% of HRIs with a similar yield of EUS and MRI and an annual risk of 0.5%. A higher rate of target lesions was reported in HRIs with specific DNA mutations.","DOI":"10.1177/2050640617752182","ISSN":"2050-6406","note":"PMID: 29881603\nPMCID: PMC5987280","title-short":"Results of surveillance in individuals at high-risk of pancreatic cancer","journalAbbreviation":"United European Gastroenterol J","language":"eng","author":[{"family":"Signoretti","given":"Marianna"},{"family":"Bruno","given":"Marco J."},{"family":"Zerboni","given":"Giulia"},{"family":"Poley","given":"Jan-Werner"},{"family":"Delle Fave","given":"Gianfranco"},{"family":"Capurso","given":"Gabriele"}],"issued":{"date-parts":[["2018",5]]}}},{"id":"BbVydael/NFPiCpG1","uris":[""],"uri":[""],"itemData":{"id":46,"type":"article-journal","title":"Screening for early pancreatic neoplasia in high-risk individuals: a prospective controlled study","container-title":"Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association","page":"766-781; quiz 665","volume":"4","issue":"6","source":"PubMed","abstract":"BACKGROUND & AIMS: Individuals with a strong family history of pancreatic cancer and persons with Peutz-Jeghers syndrome (PJS) have an increased risk for pancreatic cancer. This study screened for early pancreatic neoplasia and compared the pancreatic abnormalities in high-risk individuals and control subjects.\nMETHODS: High-risk individuals with PJS or a strong family history of pancreatic cancer were prospectively evaluated with baseline and 12-month computed tomography (CT) scan and endoscopic ultrasonography (EUS). If EUS was abnormal, EUS-fine-needle aspiration and endoscopic retrograde cholangiopancreatography (ERCP) were performed. Surgery was offered to patients with potentially neoplastic lesions. Radiologic findings and pathologic diagnoses were compared. Patients undergoing EUS and/or ERCP for benign non-pancreatic indications were concurrently enrolled as control subjects.\nRESULTS: Seventy-eight high-risk patients (72 from familial pancreatic cancer kindreds, 6 PJS) and 149 control patients were studied. To date, 8 patients with pancreatic neoplasia have been confirmed by surgery or fine-needle aspiration (10% yield of screening); 6 patients had 8 benign intraductal papillary mucinous neoplasms (IPMNs), 1 had an IPMN that progressed to invasive ductal adenocarcinoma, and 1 had pancreatic intraepithelial neoplasia. EUS and CT also diagnosed 3 patients with 5 extrapancreatic neoplasms. At EUS and ERCP abnormalities suggestive of chronic pancreatitis were more common in high-risk patients than in control subjects.\nCONCLUSIONS: Screening EUS and CT diagnosed significant asymptomatic pancreatic and extrapancreatic neoplasms in high-risk individuals. IPMN should be considered a part of the phenotype of familial pancreatic cancer. Abnormalities suggestive of chronic pancreatitis are identified more commonly at EUS and ERCP in high-risk individuals.","DOI":"10.1016/j.cgh.2006.02.005","ISSN":"1542-3565","note":"PMID: 16682259","title-short":"Screening for early pancreatic neoplasia in high-risk individuals","journalAbbreviation":"Clin. Gastroenterol. Hepatol.","language":"eng","author":[{"family":"Canto","given":"Marcia Irene"},{"family":"Goggins","given":"Michael"},{"family":"Hruban","given":"Ralph H."},{"family":"Petersen","given":"Gloria M."},{"family":"Giardiello","given":"Francis M."},{"family":"Yeo","given":"Charles"},{"family":"Fishman","given":"Elliott K."},{"family":"Brune","given":"Kieran"},{"family":"Axilbund","given":"Jennifer"},{"family":"Griffin","given":"Constance"},{"family":"Ali","given":"Syed"},{"family":"Richman","given":"Jeffrey"},{"family":"Jagannath","given":"Sanjay"},{"family":"Kantsevoy","given":"Sergey V."},{"family":"Kalloo","given":"Anthony N."}],"issued":{"date-parts":[["2006",6]]}}},{"id":"BbVydael/w0k4vP4h","uris":[""],"uri":[""],"itemData":{"id":113,"type":"article-journal","title":"Methods and outcomes of screening for pancreatic adenocarcinoma in high-risk individuals","container-title":"World Journal of Gastrointestinal Endoscopy","page":"833-842","volume":"7","issue":"9","source":"PubMed","abstract":"Pancreatic ductal adenocarcinoma (PDAC) is a lethal neoplasia, for which secondary prevention (i.e., screening) is advisable for high-risk individuals with \"familiar pancreatic cancer\" and with other specific genetic syndromes (Peutz-Jeghers, p16, BRCA2, PALB and mismatch repair gene mutation carriers). There is limited evidence regarding the accuracy of screening tests, their acceptability, costs and availability, and agreement on whom to treat. Successful target of screening are small resectable PDAC, intraductal papillary mucinous neoplasms with high-grade dysplasia and advanced pancreatic intraepithelial neoplasia. Both magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS) are employed for screening, and the overall yield for pre-malignant or malignant pancreatic lesions is of about 20% with EUS and 14% with MRI/magnetic resonance colangiopancreatography. EUS performs better for solid and MRI for cystic lesions. However, only 2% of these detected lesions can be considered a successful target, and there are insufficient data demonstrating that resection of benign or low grade lesions improves survival. Many patients in the published studies therefore seemed to have received an overtreatment by undergoing surgery. It is crucial to better stratify the risk of malignancy individually, and to better define optimal screening intervals and methods either with computerized tools or molecular biomarkers, possibly in large multicentre studies. At the moment, screening should be carefully performed within research protocols at experienced centres, offering involved individuals medical and psychological advice.","DOI":"10.4253/wjge.v7.i9.833","ISSN":"1948-5190","note":"PMID: 26240684\nPMCID: PMC4515417","journalAbbreviation":"World J Gastrointest Endosc","language":"eng","author":[{"family":"Capurso","given":"Gabriele"},{"family":"Signoretti","given":"Marianna"},{"family":"Valente","given":"Roberto"},{"family":"Arnelo","given":"Urban"},{"family":"Lohr","given":"Matthias"},{"family":"Poley","given":"Jan-Werner"},{"family":"Delle Fave","given":"Gianfranco"},{"family":"Del Chiaro","given":"Marco"}],"issued":{"date-parts":[["2015",7,25]]}}},{"id":"BbVydael/KLfm1MxF","uris":[""],"uri":[""],"itemData":{"id":38,"type":"article-journal","title":"A multicentre comparative prospective blinded analysis of EUS and MRI for screening of pancreatic cancer in high-risk individuals","container-title":"Gut","page":"1505-1513","volume":"65","issue":"9","source":"PubMed","abstract":"OBJECTIVE: Endoscopic ultrasonography (EUS) and MRI are promising tests to detect precursors and early-stage pancreatic ductal adenocarcinoma (PDAC) in high-risk individuals (HRIs). It is unclear which screening technique is to be preferred. We aimed to compare the efficacy of EUS and MRI in their ability to detect clinically relevant lesions in HRI.\nDESIGN: Multicentre prospective study. The results of 139 asymptomatic HRI (>10-fold increased risk) undergoing first-time screening by EUS and MRI are described. Clinically relevant lesions were defined as solid lesions, main duct intraductal papillary mucinous neoplasms and cysts ≥10?mm. Results were compared in a blinded, independent fashion.\nRESULTS: Two solid lesions (mean size 9?mm) and nine cysts ≥10?mm (mean size 17?mm) were detected in nine HRI (6%). Both solid lesions were detected by EUS only and proved to be a stage I PDAC and a multifocal pancreatic intraepithelial neoplasia 2. Of the nine cysts ≥10?mm, six were detected by both imaging techniques and three were detected by MRI only. The agreement between EUS and MRI for the detection of clinically relevant lesions was 55%. Of these clinically relevant lesions detected by both techniques, there was a good agreement for location and size.\nCONCLUSIONS: EUS and/or MRI detected clinically relevant pancreatic lesions in 6% of HRI. Both imaging techniques were complementary rather than interchangeable: contrary to EUS, MRI was found to be very sensitive for the detection of cystic lesions of any size; MRI, however, might have some important limitations with regard to the timely detection of solid lesions.","DOI":"10.1136/gutjnl-2014-308008","ISSN":"1468-3288","note":"PMID: 25986944","journalAbbreviation":"Gut","language":"eng","author":[{"family":"Harinck","given":"F."},{"family":"Konings","given":"I. C. a. W."},{"family":"Kluijt","given":"I."},{"family":"Poley","given":"J. W."},{"family":"Hooft","given":"J. E.","non-dropping-particle":"van"},{"family":"Dullemen","given":"H. M.","non-dropping-particle":"van"},{"family":"Nio","given":"C. Y."},{"family":"Krak","given":"N. C."},{"family":"Hermans","given":"J. J."},{"family":"Aalfs","given":"C. M."},{"family":"Wagner","given":"A."},{"family":"Sijmons","given":"R. H."},{"family":"Biermann","given":"K."},{"family":"Eijck","given":"C. H.","non-dropping-particle":"van"},{"family":"Gouma","given":"D. J."},{"family":"Dijkgraaf","given":"M. G. W."},{"family":"Fockens","given":"P."},{"family":"Bruno","given":"M. J."},{"literal":"Dutch research group on pancreatic cancer surveillance in high-risk individuals"}],"issued":{"date-parts":[["2016"]]}}},{"id":"BbVydael/uPpbB5zq","uris":[""],"uri":[""],"itemData":{"id":192,"type":"article-journal","title":"Pancreatic cancer screening in high-risk individuals with germline genetic mutations","container-title":"Gastrointestinal Endoscopy","page":"1443-1450","volume":"87","issue":"6","source":"PubMed","abstract":"BACKGROUND AND AIMS: Pancreatic cancer (PC) is a deadly disease that is most commonly diagnosed at an incurable stage. Different high-risk genetic variants and cancer syndromes increase the lifetime risk of developing PC. This study aims to assess the yield of initial PC screening in patients with high-risk germline mutations.\nMETHODS: Asymptomatic adults underwent PC screening by EUS, magnetic resonance imaging, or CT during a 10-year period and were retrospectively identified. High-risk individuals were defined as carrying germline mutations in BRCA1, BRCA2, p53 (Li-Fraumeni), STK11 (Peutz-Jeghers), MSH2 (Lynch), ATM (ataxia-telangiectasia), or APC (familial adenomatous polyposis). Patients without germline mutations were excluded.\nRESULTS: In total, 86 patients met the study criteria. The median age was 48.5 years (interquartile range, 40-58), 79.1% (68) were women, and 43.0% (37) had a family history of PC. The genetic mutations were BRCA2 (50,?58.1%), BRCA1 (14, 16.3%), p53 (12, 14.0%), STK11 (5, 5.8%), MSH2 (3, 3.5%), ATM (1, 1.2%), and APC (1,?1.2%). Screening detected a pancreatic abnormality (PA) in 26.7% (23/86), including cysts (11, 47.8%), hyperechoic strands and foci (10, 43.5%), and mild pancreatic duct dilation (2, 8.7%). Patients older than 60 years were more likely to have a PA detected (P?= .043). EUS detected more PAs than magnetic resonance imaging or CT. No?cases of PC were diagnosed by screening or during follow-up (median, 29.8 months; interquartile range, 21.7-43.5).\nCONCLUSIONS: Unless indicated otherwise by family or personal history, PC screening under the age of 50 is low yield. Linear EUS may be the preferred modality for initial PC screening.","DOI":"10.1016/j.gie.2017.12.019","ISSN":"1097-6779","note":"PMID: 29309780","journalAbbreviation":"Gastrointest. Endosc.","language":"eng","author":[{"family":"DaVee","given":"Tomas"},{"family":"Coronel","given":"Emmanuel"},{"family":"Papafragkakis","given":"Charilaos"},{"family":"Thaiudom","given":"Sayam"},{"family":"Lanke","given":"Gandhi"},{"family":"Chakinala","given":"Raja C."},{"family":"Nogueras González","given":"Graciela M."},{"family":"Bhutani","given":"Manoop S."},{"family":"Ross","given":"William A."},{"family":"Weston","given":"Brian R."},{"family":"Lee","given":"Jeffrey H."}],"issued":{"date-parts":[["2018",6]]}}},{"id":"BbVydael/Y03HYTFt","uris":[""],"uri":[""],"itemData":{"id":136,"type":"article-journal","title":"German national case collection for familial pancreatic cancer (FaPaCa): ten years experience","container-title":"Familial Cancer","page":"323-330","volume":"10","issue":"2","source":"PubMed","abstract":"Familial pancreatic cancer (FPC) is a rare hereditary tumor syndrome. The 10-years experience of the national case collection for familial pancreatic cancer of Germany (FaPaCa) is reported. Since 1999 FaPaCa has collected families with at least two first-degree relatives with confirmed pancreatic cancer (PC), who did not fulfill the criteria of other hereditary tumor syndromes. Histopathological verification of tumor diagnoses, and genetic counseling were prerequisites for enrollment of families in FaPaCa. 94 of 452 evaluated families fulfilled the criteria for partaking in FaPaCa. PC represented the sole tumor entity in 38 (40%) families. In 56 families additional tumor types occurred, including breast cancer (n?=?28), colon cancer (n?=?20) and lung cancer (n?=?11). In 70 (74%) families the pattern of inheritance was consistent with an autosomal dominant trait. Compared to the preceding generation, a younger age of onset was observed in the offspring of PC patients (median: 57 vs. 69?years), indicating anticipation. Mutation analyses of BRCA2, PALB2, CDKN2a, RNASEL, STK11, NOD2, CHEK2 and PALLD, revealed deleterious causative germline mutations of BRCA2 and PALB2 in 2 of 70 (3%) and 2 of 41 (4.9%) German FPC families, respectively. Prospective PC screening with EUS, MRI and MRCP detected precancerous lesions (IPMN, multifocal PanIN2/3) or carcinoma in 5.5% (4 of 72) to 12.5% (9 of 72) of individuals at risk, depending on histological verification. Appropriate inclusion of families at high risk for PC in registries, such as FaPaCa, provides a unique and excellent tool to gain clinical and genetic knowledge of FPC. Focused research projects can be conducted most efficiently, when data of different FPC registries are combined.","DOI":"10.1007/s10689-010-9414-x","ISSN":"1573-7292","note":"PMID: 21207249","title-short":"German national case collection for familial pancreatic cancer (FaPaCa)","journalAbbreviation":"Fam. Cancer","language":"eng","author":[{"family":"Schneider","given":"Ralph"},{"family":"Slater","given":"Emily P."},{"family":"Sina","given":"Mercede"},{"family":"Habbe","given":"Nils"},{"family":"Fendrich","given":"Volker"},{"family":"Matth?i","given":"Elvira"},{"family":"Langer","given":"Peter"},{"family":"Bartsch","given":"Detlef K."}],"issued":{"date-parts":[["2011",6]]}}}],"schema":""} [4,10,18,23,26,27,39,40]. Of note, most studies that reported a low rate of EUS-detected abnormalities did not consider chronic pancreatitis-like parenchymal changes. Pancreatic cystic lesions identified in HRI are mainly IPMN, which are more frequent in HRI (13%-20%) than in the general population (1%-5%) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"qYL38HaV","properties":{"formattedCitation":"\\super [18,26,41,42]\\nosupersub{}","plainCitation":"[18,26,41,42]","noteIndex":0},"citationItems":[{"id":"BbVydael/C3zHNTfr","uris":[""],"uri":[""],"itemData":{"id":95,"type":"article-journal","title":"Results of surveillance in individuals at high-risk of pancreatic cancer: A systematic review and meta-analysis","container-title":"United European Gastroenterology Journal","page":"489-499","volume":"6","issue":"4","source":"PubMed","abstract":"Background: Data on surveillance for pancreatic ductal adenocarcinoma (PDAC) in high-risk individuals (HRIs) with \"familial pancreatic cancer\" (FPC) and specific syndromes are limited and heterogeneous.\nObjective: We conducted a systematic review and meta-analysis of PDAC surveillance studies in HRIs.\nMethods: Prevalence of solid/cystic pancreatic lesions and of lesions considered a successful target of surveillance (proven resectable PDAC and high-grade precursors) was pooled across studies. The rate of lesions diagnosed by endoscopic ultrasonography (EUS)/magnetic resonance imaging (MRI) and across different HRI groups was calculated.\nResults: Sixteen studies incorporating 1588 HRIs were included. The pooled prevalence of pancreatic solid and cystic lesions was 5.8% and 20.2%, respectively. The pooled prevalence of patients with lesions considered a successful target of surveillance was 3.3%, being similar to EUS or MRI and varying across subgroups, being 3% in FPC, 4% in hereditary pancreatitis, 5% in familial melanoma, 6.3% in hereditary breast/ovarian cancer, and 12.2% in Peutz-Jeghers syndrome. The pooled estimated rate of lesions considered a successful target of surveillance during follow-up was 5/1000 person-years.\nConclusion: Surveillance programs identify successful target lesions in 3.3% of HRIs with a similar yield of EUS and MRI and an annual risk of 0.5%. A higher rate of target lesions was reported in HRIs with specific DNA mutations.","DOI":"10.1177/2050640617752182","ISSN":"2050-6406","note":"PMID: 29881603\nPMCID: PMC5987280","title-short":"Results of surveillance in individuals at high-risk of pancreatic cancer","journalAbbreviation":"United European Gastroenterol J","language":"eng","author":[{"family":"Signoretti","given":"Marianna"},{"family":"Bruno","given":"Marco J."},{"family":"Zerboni","given":"Giulia"},{"family":"Poley","given":"Jan-Werner"},{"family":"Delle Fave","given":"Gianfranco"},{"family":"Capurso","given":"Gabriele"}],"issued":{"date-parts":[["2018",5]]}}},{"id":"BbVydael/w0k4vP4h","uris":[""],"uri":[""],"itemData":{"id":113,"type":"article-journal","title":"Methods and outcomes of screening for pancreatic adenocarcinoma in high-risk individuals","container-title":"World Journal of Gastrointestinal Endoscopy","page":"833-842","volume":"7","issue":"9","source":"PubMed","abstract":"Pancreatic ductal adenocarcinoma (PDAC) is a lethal neoplasia, for which secondary prevention (i.e., screening) is advisable for high-risk individuals with \"familiar pancreatic cancer\" and with other specific genetic syndromes (Peutz-Jeghers, p16, BRCA2, PALB and mismatch repair gene mutation carriers). There is limited evidence regarding the accuracy of screening tests, their acceptability, costs and availability, and agreement on whom to treat. Successful target of screening are small resectable PDAC, intraductal papillary mucinous neoplasms with high-grade dysplasia and advanced pancreatic intraepithelial neoplasia. Both magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS) are employed for screening, and the overall yield for pre-malignant or malignant pancreatic lesions is of about 20% with EUS and 14% with MRI/magnetic resonance colangiopancreatography. EUS performs better for solid and MRI for cystic lesions. However, only 2% of these detected lesions can be considered a successful target, and there are insufficient data demonstrating that resection of benign or low grade lesions improves survival. Many patients in the published studies therefore seemed to have received an overtreatment by undergoing surgery. It is crucial to better stratify the risk of malignancy individually, and to better define optimal screening intervals and methods either with computerized tools or molecular biomarkers, possibly in large multicentre studies. At the moment, screening should be carefully performed within research protocols at experienced centres, offering involved individuals medical and psychological advice.","DOI":"10.4253/wjge.v7.i9.833","ISSN":"1948-5190","note":"PMID: 26240684\nPMCID: PMC4515417","journalAbbreviation":"World J Gastrointest Endosc","language":"eng","author":[{"family":"Capurso","given":"Gabriele"},{"family":"Signoretti","given":"Marianna"},{"family":"Valente","given":"Roberto"},{"family":"Arnelo","given":"Urban"},{"family":"Lohr","given":"Matthias"},{"family":"Poley","given":"Jan-Werner"},{"family":"Delle Fave","given":"Gianfranco"},{"family":"Del Chiaro","given":"Marco"}],"issued":{"date-parts":[["2015",7,25]]}}},{"id":"BbVydael/i0AT7YFQ","uris":[""],"uri":[""],"itemData":{"id":151,"type":"article-journal","title":"Are BRCA1 and BRCA2 gene mutation patients underscreened for pancreatic adenocarcinoma?","container-title":"Journal of Surgical Oncology","source":"PubMed","abstract":"BACKGROUND: Breast cancer (BRCA) mutations account for the highest proportion of hereditary causes of pancreatic ductal adenocarcinoma (PDAC). Screening is currently recommended only for patients with one first-degree relative or two family members with PDAC. We hypothesized that screening all BRCA1/2 patients would identify a higher rate of pancreatic abnormalities.\nMETHODS: All BRCA1/2 patients at a single academic center were retrospectively reviewed (2005-2015). Pancreatic abnormalities were defined on cross-sectional imaging as pancreatic neoplasm (cystic/solid) or main-duct dilation.\nRESULTS: Two hundred and four patients were identified with BRCA mutations. Forty-seven (40%) had abdominal imaging (20 computerized tomography and 27 magnetic resonance imaging). Twenty-one percent had pancreatic abnormalities (PDAC [n?=?2] and intraductal papillary mucinous neoplasm [IPMN; n?=?8]). The prevalence of pancreatic abnormalities and IPMN was higher in BRCA2 patients than in the general population (21% vs 8% and 17% vs 1%; P?=?0.0007 and P?<?0.0001, respectively), with no influence of family history. Similarly, BRCA1 patients had an increased prevalence of IPMN (8.3% vs 1%; P?<?0.0001).\nCONCLUSIONS: In this series, 4% and 17% of BRCA2 patients developed PDAC and IPMN, respectively. Eight percent of BRCA1 patients developed IPMN. Under current recommended screening, 60% of BRCA1/2 patients had incompletely pancreatic assessment. With no influence of family history, this study suggests all BRCA1/2 patients should undergo a high-risk screening protocol that will identify a higher rate of precancerous pancreatic neoplasms amenable to curative resection.","DOI":"10.1002/jso.25376","ISSN":"1096-9098","note":"PMID: 30636051","journalAbbreviation":"J Surg Oncol","language":"eng","author":[{"family":"Roch","given":"Alexandra M."},{"family":"Schneider","given":"Justine"},{"family":"Carr","given":"Rosalie A."},{"family":"Lancaster","given":"William P."},{"family":"House","given":"Michael G."},{"family":"Zyromski","given":"Nicholas J."},{"family":"Nakeeb","given":"Attila"},{"family":"Schmidt","given":"C. Max"},{"family":"Ceppa","given":"Eugene P."}],"issued":{"date-parts":[["2019",1,12]]}}},{"id":"BbVydael/skZ3C2fW","uris":[""],"uri":[""],"itemData":{"id":149,"type":"article-journal","title":"Estimation of the prevalence of asymptomatic pancreatic cysts in the population of San Marino","container-title":"Pancreatology: official journal of the International Association of Pancreatology (IAP) ... [et al.]","page":"417-422","volume":"15","issue":"4","source":"PubMed","abstract":"BACKGROUND: There has been a dramatic increase in the number of pancreatic cystic lesions observed in the past two decades but data regarding the prevalence of cysts in the general population are lacking.\nMETHODS: All the individuals who undergo CT at the San Marino State Hospital are residents of the Republic of San Marino; their demographic distribution is available and precise. CT scans carried out over 1?year at the State Hospital were reviewed for asymptomatic pancreatic cysts.\nRESULTS: 1061 relevant CT scans were carried out on 814 patients; 762 individuals were eligible for the study and 650 patients underwent contrast-enhanced CT. Thirty-five patients had at least one cyst at contrast-enhanced CT (5.4%). The prevalence of cysts increased with increasing age up to 13.4% (95% CI 6.6-20) in individuals 80-89 years of age (p?<?.001). Cyst prevalence was significantly higher in patients who underwent CT for malignancy (p?=?.038) but this difference was no longer significant in multivariate analysis. The odds of a cyst being present increased by 1.05 (95% CI 1.02-1.09) for each increasing year of age (p?=?.002). Approximately a quarter of the patients with cysts died within 1 year after CT from non pancreas-related disease. The estimated standardized age-adjusted cyst prevalence is 2194 per 100,000 people.\nCONCLUSIONS: The likelihood of having a pancreatic cyst correlates with increasing age, not with the presence of extra-pancreatic malignancies. The estimated prevalence of CT-detectable asymptomatic pancreatic cysts in the general population is 2.2%.","DOI":"10.1016/j.pan.2015.05.461","ISSN":"1424-3911","note":"PMID: 26028332","journalAbbreviation":"Pancreatology","language":"eng","author":[{"family":"Zanini","given":"Nicola"},{"family":"Giordano","given":"Marco"},{"family":"Smerieri","given":"Elia"},{"family":"Cipolla d'Abruzzo","given":"Giulio"},{"family":"Guidi","given":"Marilyn"},{"family":"Pazzaglini","given":"Giorgio"},{"family":"De Luca","given":"Fiorella"},{"family":"Chiaruzzi","given":"Giorgia"},{"family":"Vitullo","given":"Giovanni"},{"family":"Piva","given":"Paolo"},{"family":"Lombardi","given":"Raffaele"},{"family":"Jovine","given":"Elio"},{"family":"Gatti","given":"Marino"},{"family":"Landolfo","given":"Giovanni"}],"issued":{"date-parts":[["2015",8]]}}}],"schema":""} [18,26,41,42]. Whether IPMN in HRI have a different course than sporadic ones is unknown, and hence their monitoring could be similar by analogy with the general population. First, the initial characterization of IPMN should search for potential high-risk stigmata (obstructive jaundice associated with cystic lesions of the head of the pancreas, enhancing mural nodules > 5 mm, main pancreatic duct > 10 mm) and worrisome features (pancreatitis, cyst > 3 cm, enhancing mural nodule < 5 mm, thickened/enhancing cyst walls, main duct size 5-9 mm, abrupt change in calibre of pancreatic duct with distal pancreatic atrophy, lymphadenopathy, increased CA19-9 serum levels, and cyst growth rate > 5 mm per 2 years) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"LZwTH15b","properties":{"formattedCitation":"\\super [43,44]\\nosupersub{}","plainCitation":"[43,44]","noteIndex":0},"citationItems":[{"id":"BbVydael/05c6dvnZ","uris":[""],"uri":[""],"itemData":{"id":156,"type":"article-journal","title":"Revisions of international consensus Fukuoka guidelines for the management of IPMN of the pancreas","container-title":"Pancreatology: official journal of the International Association of Pancreatology (IAP) ... [et al.]","page":"738-753","volume":"17","issue":"5","source":"PubMed","abstract":"The management of intraductal papillary mucinous neoplasm (IPMN) continues to evolve. In particular, the indications for resection of branch duct IPMN have changed from early resection to more deliberate observation as proposed by the international consensus guidelines of 2006 and 2012. Another guideline proposed by the American Gastroenterological Association in 2015 restricted indications for surgery more stringently and recommended physicians to stop surveillance if no significant change had occurred in a pancreatic cyst after five years of surveillance, or if a patient underwent resection and a non-malignant IPMN was found. Whether or not it is safe to do so, as well as the method and interval of surveillance, has generated substantial debate. Based on a consensus symposium held during the meeting of the International Association of Pancreatology in Sendai, Japan, in 2016, the working group has revised the guidelines regarding prediction of invasive carcinoma and high-grade dysplasia, surveillance, and postoperative follow-up of IPMN. As the working group did not recognize the need for major revisions of the guidelines, we made only minor revisions and added most recent articles where appropriate. The present guidelines include updated information and recommendations based on our current understanding, and highlight issues that remain controversial or where further research is required.","DOI":"10.1016/j.pan.2017.07.007","ISSN":"1424-3911","note":"PMID: 28735806","journalAbbreviation":"Pancreatology","language":"eng","author":[{"family":"Tanaka","given":"Masao"},{"family":"Fernández-Del Castillo","given":"Carlos"},{"family":"Kamisawa","given":"Terumi"},{"family":"Jang","given":"Jin Young"},{"family":"Levy","given":"Philippe"},{"family":"Ohtsuka","given":"Takao"},{"family":"Salvia","given":"Roberto"},{"family":"Shimizu","given":"Yasuhiro"},{"family":"Tada","given":"Minoru"},{"family":"Wolfgang","given":"Christopher L."}],"issued":{"date-parts":[["2017",10]]}}},{"id":"BbVydael/6RUhPm00","uris":[""],"uri":[""],"itemData":{"id":153,"type":"article-journal","title":"European evidence-based guidelines on pancreatic cystic neoplasms","container-title":"Gut","page":"789-804","volume":"67","issue":"5","source":"PubMed","abstract":"Evidence-based guidelines on the management of pancreatic cystic neoplasms (PCN) are lacking. This guideline is a joint initiative of the European Study Group on Cystic Tumours of the Pancreas, United European Gastroenterology, European Pancreatic Club, European-African Hepato-Pancreato-Biliary Association, European Digestive Surgery, and the European Society of Gastrointestinal Endoscopy. It replaces the 2013 European consensus statement guidelines on PCN. European and non-European experts performed systematic reviews and used GRADE methodology to answer relevant clinical questions on nine topics (biomarkers, radiology, endoscopy, intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), serous cystic neoplasm, rare cysts, (neo)adjuvant treatment, and pathology). Recommendations include conservative management, relative and absolute indications for surgery. A conservative approach is recommended for asymptomatic MCN and IPMN measuring <40 mm without an enhancing nodule. Relative indications for surgery in IPMN include a main pancreatic duct (MPD) diameter between 5 and 9.9 mm or a cyst diameter ≥40 mm. Absolute indications for surgery in IPMN, due to the high-risk of malignant transformation, include jaundice, an enhancing mural nodule >5 mm, and MPD diameter >10 mm. Lifelong follow-up of IPMN is recommended in patients who are fit for surgery. The European evidence-based guidelines on PCN aim to improve the diagnosis and management of PCN.","DOI":"10.1136/gutjnl-2018-316027","ISSN":"1468-3288","note":"PMID: 29574408\nPMCID: PMC5890653","journalAbbreviation":"Gut","language":"eng","author":[{"literal":"European Study Group on Cystic Tumours of the Pancreas"}],"issued":{"date-parts":[["2018",5]]}}}],"schema":""} [43,44]. These features are highly important for deciding on surgery because their presence is associated with an increased probability of finding invasive PC or HGD on the resected specimen ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"KponxENl","properties":{"formattedCitation":"\\super [11]\\nosupersub{}","plainCitation":"[11]","noteIndex":0},"citationItems":[{"id":"BbVydael/iMJ7y1A2","uris":[""],"uri":[""],"itemData":{"id":33,"type":"article-journal","title":"Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma: a patient-level meta-analysis and proposition of the Beaujon score","container-title":"United European Gastroenterology Journal","page":"205064061882491","source":"Crossref","DOI":"10.1177/2050640618824910","ISSN":"2050-6406, 2050-6414","title-short":"Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma","language":"en","author":[{"family":"Mestier","given":"Louis","non-dropping-particle":"de"},{"family":"Muller","given":"Marie"},{"family":"Cros","given":"Jér?me"},{"family":"Vullierme","given":"Marie-Pierre"},{"family":"Vernerey","given":"Dewi"},{"family":"Maire","given":"Frédérique"},{"family":"Dokmak","given":"Safi"},{"family":"Rebours","given":"Vinciane"},{"family":"Sauvanet","given":"Alain"},{"family":"Lévy","given":"Philippe"},{"family":"Hammel","given":"Pascal"}],"issued":{"date-parts":[["2019",1,12]]}}}],"schema":""} [11]. EUS has been shown to be the best technique for the early detection of malignancy in patients with IPMN ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"hBedaqF2","properties":{"formattedCitation":"\\super [45]\\nosupersub{}","plainCitation":"[45]","noteIndex":0},"citationItems":[{"id":"BbVydael/NZh776au","uris":[""],"uri":[""],"itemData":{"id":197,"type":"article-journal","title":"Value of EUS in early detection of pancreatic ductal adenocarcinomas in patients with intraductal papillary mucinous neoplasms","container-title":"Endoscopy","page":"22-29","volume":"46","issue":"1","source":"PubMed","abstract":"BACKGROUND AND STUDY AIMS: Pancreatic ductal adenocarcinomas (PDAC) sometimes arise in patients with intraductal papillary mucinous neoplasms (IPMNs). This study examined the incidence of PDACs concomitant to or derived from branch duct IPMNs. The usefulness of endoscopic ultrasonography (EUS) relative to other imaging methods for detecting these tumors was also assessed.\nPATIENTS AND METHODS: This retrospective study used data from clinical records and imaging studies that were collected prospectively. During 2001-2009, 167 consecutive patients with IPMNs underwent EUS, ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI). The 102 patients whose branch duct IPMNs lacked mural nodules/symptoms and thus did not qualify for resection were followed up by semiannual EUS and annual ultrasonography, CT, and MRI. The sensitivity and specificity with which the four modalities detected IPMN-derived and -concomitant PDACs at the first examination and throughout the study period were evaluated. The rate of PDAC development during follow-up was analyzed by the Kaplan-Meier method.\nRESULTS: A total of 17 IPMN-derived and 11 IPMN-concomitant PDACs were diagnosed at the first examination. Lesions that did not qualify for resection or chemotherapy were followed up for a median of 42 months. Seven IPMN-concomitant PDACs and no IPMN-derived PDACs were detected during follow-up. The 3- and 5-year rates of IPMN-concomitant PDAC development were 4.0% and 8.8%, respectively. At the first examination, EUS was superior to other imaging modalities in terms of IPMN-derived and -concomitant PDAC detection. Throughout the study period, including follow-up, EUS was significantly better at detecting IPMN-concomitant PDACs than the other modalities.\nCONCLUSIONS: IPMN-concomitant PDACs are quite often found at diagnosis and during follow-up. EUS examination of the whole pancreas plays an important role in the management of IPMNs as it allows the early detection of these small invasive carcinomas.","DOI":"10.1055/s-0033-1353603","ISSN":"1438-8812","note":"PMID: 24218310","journalAbbreviation":"Endoscopy","language":"eng","author":[{"family":"Kamata","given":"Ken"},{"family":"Kitano","given":"Masayuki"},{"family":"Kudo","given":"Masatoshi"},{"family":"Sakamoto","given":"Hiroki"},{"family":"Kadosaka","given":"Kumpei"},{"family":"Miyata","given":"Takeshi"},{"family":"Imai","given":"Hajime"},{"family":"Maekawa","given":"Kiyoshi"},{"family":"Chikugo","given":"Takaaki"},{"family":"Kumano","given":"Masashi"},{"family":"Hyodo","given":"Tomoko"},{"family":"Murakami","given":"Takamichi"},{"family":"Chiba","given":"Yasutaka"},{"family":"Takeyama","given":"Yoshifumi"}],"issued":{"date-parts":[["2014",1]]}}}],"schema":""} [45]. Nevertheless, the entire pancreatic parenchyma is at risk of PC, which can occur away from the cysts ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"mcyjftvX","properties":{"formattedCitation":"\\super [46]\\nosupersub{}","plainCitation":"[46]","noteIndex":0},"citationItems":[{"id":"BbVydael/QWhYTM0n","uris":[""],"uri":[""],"itemData":{"id":354,"type":"article-journal","title":"IPMNs with co-occurring invasive cancers: neighbours but not always relatives","container-title":"Gut","page":"1652-1662","volume":"67","issue":"9","source":"PubMed","abstract":"OBJECTIVE: Intraductal papillary mucinous neoplasms (IPMNs) are precursor lesions that can give rise to invasive pancreatic carcinoma. Although approximately 8% of patients with resected pancreatic ductal adenocarcinoma have a co-occurring IPMN, the precise genetic relationship between these two lesions has not been systematically investigated.\nDESIGN: We analysed all available patients with co-occurring IPMN and invasive intrapancreatic carcinoma over a 10-year period at a single institution. For each patient, we separately isolated DNA from the carcinoma, adjacent IPMN and distant IPMN and performed targeted next generation sequencing of a panel of pancreatic cancer driver genes. We then used the identified mutations to infer the relatedness of the IPMN and co-occurring invasive carcinoma in each patient.\nRESULTS: We analysed co-occurring IPMN and invasive carcinoma from 61 patients with IPMN/ductal adenocarcinoma as well as 13 patients with IPMN/colloid carcinoma and 7 patients with IPMN/carcinoma of the ampullary region. Of the patients with co-occurring IPMN and ductal adenocarcinoma, 51% were likely related. Surprisingly, 18% of co-occurring IPMN and ductal adenocarcinomas were likely independent, suggesting that the carcinoma arose from an independent precursor. By contrast, all colloid carcinomas were likely related to their associated IPMNs. In addition, these analyses showed striking genetic heterogeneity in IPMNs, even with respect to well-characterised driver genes.\nCONCLUSION: This study demonstrates a higher prevalence of likely independent co-occurring IPMN and ductal adenocarcinoma than previously appreciated. These findings have important implications for molecular risk stratification of patients with IPMN.","DOI":"10.1136/gutjnl-2017-315062","ISSN":"1468-3288","note":"PMID: 29500184","title-short":"IPMNs with co-occurring invasive cancers","journalAbbreviation":"Gut","language":"eng","author":[{"family":"Felsenstein","given":"Matth?us"},{"family":"No?","given":"Micha?l"},{"family":"Masica","given":"David L."},{"family":"Hosoda","given":"Waki"},{"family":"Chianchiano","given":"Peter"},{"family":"Fischer","given":"Catherine G."},{"family":"Lionheart","given":"Gemma"},{"family":"Brosens","given":"Lodewijk A. A."},{"family":"Pea","given":"Antonio"},{"family":"Yu","given":"Jun"},{"family":"Gemenetzis","given":"Georgios"},{"family":"Groot","given":"Vincent P."},{"family":"Makary","given":"Martin A."},{"family":"He","given":"Jin"},{"family":"Weiss","given":"Matthew J."},{"family":"Cameron","given":"John L."},{"family":"Wolfgang","given":"Christopher L."},{"family":"Hruban","given":"Ralph H."},{"family":"Roberts","given":"Nicholas J."},{"family":"Karchin","given":"Rachel"},{"family":"Goggins","given":"Michael G."},{"family":"Wood","given":"Laura D."}],"issued":{"date-parts":[["2018"]]}}}],"schema":""} [46]. Thus, surveillance should not focus on pancreatic cysts alone. However, all cystic lesions found in HRI are not IPMN (but may be other benign cysts such as serous cystadenomas) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"9lLCtgof","properties":{"formattedCitation":"\\super [15,30,31]\\nosupersub{}","plainCitation":"[15,30,31]","noteIndex":0},"citationItems":[{"id":"BbVydael/TT8LQAKI","uris":[""],"uri":[""],"itemData":{"id":79,"type":"article-journal","title":"Five years of prospective screening of high-risk individuals from families with familial pancreatic cancer","container-title":"Gut","page":"1410-1418","volume":"58","issue":"10","source":"PubMed","abstract":"OBJECTIVE: Familial pancreatic cancer (FPC) accounts for approximately 3% of all pancreatic cancer (PC) cases. It has been suggested that high-risk individuals (HRIs) should be offered a screening programme.\nAIM: To evaluate the diagnostic yield of a prospective screening programme in HRIs from families with FPC over a period of 5 years.\nMETHODS: HRIs of families with FPC of the National German Familial Pancreatic Cancer Registry (FaPaCa) were counselled and enrolled in a prospective, board-approved PC screening programme. Screening included clinical examination, laboratory tests, endoscopic ultrasound (EUS) and MRI with magnetic resonance cholangiopancreaticography (MRCP) and MR angiography.\nRESULTS: Between June 2002 and December 2007, 76 HRIs of families with FPC took part in the screening programme with a total of 182 examination visits. Twenty-eight patients revealed abnormalities in EUS (n = 25) and/or MR/MRCP (n = 12). In 7 patients fine needle aspiration cytology was performed. Operative pancreatic explorations were performed in 7 individuals, resulting in limited resections in 6 cases. Histopathological examination of the resected specimens showed serous oligocystic adenomas (n = 3), pancreatic intraepithelial neoplasia 1 (PanIN1) lesions with lobular fibrosis (n = 1), PanIN2 lesions (n = 1) and PanIN1 lesion plus a gastric type intraductal papillary mucinous neoplasm (IPMN) (n = 1).\nCONCLUSIONS: In FPC an EUS/MR/MRCP-based screening programme leads to the detection of potential precursor lesions of PC. However, the yield of an extensive screening programme is low, especially since the tumourigenic value of low grade PanIN lesions is not yet defined. Taking into account the enormous psychological stress for the tested individual and the high costs, a general PC screening in HRIs is not justified.","DOI":"10.1136/gut.2008.171611","ISSN":"1468-3288","note":"PMID: 19470496","journalAbbreviation":"Gut","language":"eng","author":[{"family":"Langer","given":"P."},{"family":"Kann","given":"P. H."},{"family":"Fendrich","given":"V."},{"family":"Habbe","given":"N."},{"family":"Schneider","given":"M."},{"family":"Sina","given":"M."},{"family":"Slater","given":"E. P."},{"family":"Heverhagen","given":"J. T."},{"family":"Gress","given":"T. M."},{"family":"Rothmund","given":"M."},{"family":"Bartsch","given":"D. K."}],"issued":{"date-parts":[["2009",10]]}}},{"id":"BbVydael/HMFnecr3","uris":[""],"uri":[""],"itemData":{"id":31,"type":"article-journal","title":"Risk of Neoplastic Progression in Individuals at High Risk for Pancreatic Cancer Undergoing Long-term Surveillance","container-title":"Gastroenterology","page":"740-751.e2","volume":"155","issue":"3","source":"PubMed","abstract":"BACKGROUND & AIMS: Screening of individuals who have a high risk of pancreatic ductal adenocarcinoma (PDAC), because of genetic factors, frequently leads to identification of pancreatic lesions. We investigated the incidence of PDAC and risk factors for neoplastic progression in individuals at high risk for PDAC enrolled in a long-term screening study.\nMETHODS: We analyzed data from 354 individuals at high risk for PDAC (based on genetic factors of family history), enrolled in Cancer of the Pancreas Screening cohort studies at tertiary care academic centers from 1998 through 2014 (median follow-up time, 5.6 years). All subjects were evaluated at study entry (baseline) by endoscopic ultrasonography and underwent surveillance with endoscopic ultrasonography, magnetic resonance imaging, and/or computed tomography. The primary endpoint was the cumulative incidence of PDAC, pancreatic intraepithelial neoplasia grade 3, or intraductal papillary mucinous neoplasm with high-grade dysplasia (HGD) after baseline. We performed multivariate Cox regression and Kaplan-Meier analyses.\nRESULTS: During the follow-up period, pancreatic lesions with worrisome features (solid mass, multiple cysts, cyst size > 3 cm, thickened/enhancing walls, mural nodule, dilated main pancreatic duct > 5 mm, or abrupt change in duct caliber) or rapid cyst growth (>4 mm/year) were detected in 68 patients (19%). Overall, 24 of 354 patients (7%) had neoplastic progression (14 PDACs and 10 HGDs) over a 16-year period; the rate of progression was 1.6%/year, and 93% had detectable lesions with worrisome features before diagnosis of the PDAC or HGD. Nine of the 10 PDACs detected during routine surveillance were resectable; a significantly higher proportion of patients with resectable PDACs survived 3?years (85%) compared with the 4 subjects with symptomatic, unresectable PDACs (25%), which developed outside surveillance (log rank P < .0001). Neoplastic progression occurred at a median age of 67 years; the median time from baseline screening until PDAC diagnosis was 4.8 years (interquartile range, 1.6-6.9 years).\nCONCLUSIONS: In a long-term (16-year) follow-up study of individuals at high-risk for PDAC, we found most PDACs detected during surveillance (9/10) to be resectable, and 85% of these patients survived for 3 years. We?identified radiologic features associated with neoplastic progression.","DOI":"10.1053/j.gastro.2018.05.035","ISSN":"1528-0012","note":"PMID: 29803839\nPMCID: PMC6120797","journalAbbreviation":"Gastroenterology","language":"eng","author":[{"family":"Canto","given":"Marcia Irene"},{"family":"Almario","given":"Jose Alejandro"},{"family":"Schulick","given":"Richard D."},{"family":"Yeo","given":"Charles J."},{"family":"Klein","given":"Alison"},{"family":"Blackford","given":"Amanda"},{"family":"Shin","given":"Eun Ji"},{"family":"Sanyal","given":"Abanti"},{"family":"Yenokyan","given":"Gayane"},{"family":"Lennon","given":"Anne Marie"},{"family":"Kamel","given":"Ihab R."},{"family":"Fishman","given":"Elliot K."},{"family":"Wolfgang","given":"Christopher"},{"family":"Weiss","given":"Matthew"},{"family":"Hruban","given":"Ralph H."},{"family":"Goggins","given":"Michael"}],"issued":{"date-parts":[["2018"]]}}},{"id":"BbVydael/Sm6GTEmo","uris":[""],"uri":[""],"itemData":{"id":70,"type":"article-journal","title":"Benefit of Surveillance for Pancreatic Cancer in High-Risk Individuals: Outcome of Long-Term Prospective Follow-Up Studies From Three European Expert Centers","container-title":"Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology","page":"2010-2019","volume":"34","issue":"17","source":"PubMed","abstract":"PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis. Hereditary factors play a role in the development of PDAC in 3% to 5% of all patients. Surveillance of high-risk groups, may facilitate detection of PDAC at an early stage. The aim of this study was to assess whether surveillance aids detection of early-stage PDAC or precursor lesions (PRLs) and improves the prognosis.\nPATIENTS AND METHODS: Screening outcomes were collected from three European centers that conduct prospective screening in high-risk groups including families with clustering of PDAC (familial pancreatic cancer [FPC]) or families with a gene defect that predisposes to PDAC. The surveillance program consisted of annual magnetic resonance imaging, magnetic resonance cholangiopancreatography, and/or endoscopic ultrasound.\nRESULTS: Four hundred eleven asymptomatic individuals participated in the surveillance programs, including 178 CDKN2A mutation carriers, 214 individuals with FPC, and 19 BRCA1/2 or PALB2 mutation carriers. PDAC was detected in 13 (7.3%) of 178 CDKN2A mutation carriers. The resection rate was 75%, and the 5-year survival rate was 24%. Two CDKN2A mutation carriers (1%) underwent surgical resection for low-risk PRL. Two individuals (0.9%) in the FPC cohort had a pancreatic tumor, including one advanced PDAC and one early grade 2 neuroendocrine tumor. Thirteen individuals with FPC (6.1%) underwent surgical resection for a suspected PRL, but only four (1.9%) had high-risk lesions (ie, high-grade intraductal papillary mucinous neoplasms or grade 3 pancreatic intraepithelial neoplasms). One BRCA2 mutation carrier was found to have PDAC, and another BRCA2 mutation carrier and a PALB2 mutation carrier underwent surgery and were found to have low-risk PRL. No serious complications occurred as consequence of the program.\nCONCLUSION: Surveillance of CDNK2A mutation carriers is relatively successful, detecting most PDACs at a resectable stage. The benefit of surveillance in families with FPC is less evident.","DOI":"10.1200/JCO.2015.64.0730","ISSN":"1527-7755","note":"PMID: 27114589","title-short":"Benefit of Surveillance for Pancreatic Cancer in High-Risk Individuals","journalAbbreviation":"J. Clin. Oncol.","language":"eng","author":[{"family":"Vasen","given":"Hans"},{"family":"Ibrahim","given":"Isaura"},{"family":"Ponce","given":"Carmen Guillen"},{"family":"Slater","given":"Emily P."},{"family":"Matth?i","given":"Elvira"},{"family":"Carrato","given":"Alfredo"},{"family":"Earl","given":"Julie"},{"family":"Robbers","given":"Kristin"},{"family":"Mil","given":"Anneke M.","non-dropping-particle":"van"},{"family":"Potjer","given":"Thomas"},{"family":"Bonsing","given":"Bert A."},{"family":"Vos Tot Nederveen Cappel","given":"Wouter H.","non-dropping-particle":"de"},{"family":"Bergman","given":"Wilma"},{"family":"Wasser","given":"Martin"},{"family":"Morreau","given":"Hans"},{"family":"Kl?ppel","given":"Günter"},{"family":"Schicker","given":"Christoph"},{"family":"Steinkamp","given":"Martin"},{"family":"Figiel","given":"Jens"},{"family":"Esposito","given":"Irene"},{"family":"Mocci","given":"Evelina"},{"family":"Vazquez-Sequeiros","given":"Enrique"},{"family":"Sanjuanbenito","given":"Alfonso"},{"family":"Mu?oz-Beltran","given":"Maria"},{"family":"Montans","given":"José"},{"family":"Langer","given":"Peter"},{"family":"Fendrich","given":"Volker"},{"family":"Bartsch","given":"Detlef K."}],"issued":{"date-parts":[["2016"]],"season":"10"}}}],"schema":""} [15,30,31]. Nevertheless, in the absence of specific worrisome criteria for non-IPMN cystic pancreatic lesions, it seems appropriate to use the abovementioned worrisome features for all cystic lesions, while it may lead to operating on benign cysts without potential pejorative evolution ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"8G6hlQzf","properties":{"formattedCitation":"\\super [11]\\nosupersub{}","plainCitation":"[11]","noteIndex":0},"citationItems":[{"id":"BbVydael/iMJ7y1A2","uris":[""],"uri":[""],"itemData":{"id":33,"type":"article-journal","title":"Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma: a patient-level meta-analysis and proposition of the Beaujon score","container-title":"United European Gastroenterology Journal","page":"205064061882491","source":"Crossref","DOI":"10.1177/2050640618824910","ISSN":"2050-6406, 2050-6414","title-short":"Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma","language":"en","author":[{"family":"Mestier","given":"Louis","non-dropping-particle":"de"},{"family":"Muller","given":"Marie"},{"family":"Cros","given":"Jér?me"},{"family":"Vullierme","given":"Marie-Pierre"},{"family":"Vernerey","given":"Dewi"},{"family":"Maire","given":"Frédérique"},{"family":"Dokmak","given":"Safi"},{"family":"Rebours","given":"Vinciane"},{"family":"Sauvanet","given":"Alain"},{"family":"Lévy","given":"Philippe"},{"family":"Hammel","given":"Pascal"}],"issued":{"date-parts":[["2019",1,12]]}}}],"schema":""} [11].Chronic-pancreatitis-like parenchymal changes (CPis) are more common in HRI (up to 67%-80%) than in the general population (15%-17%) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"18rxoCAl","properties":{"formattedCitation":"\\super [12,23,47\\uc0\\u8211{}49]\\nosupersub{}","plainCitation":"[12,23,47–49]","noteIndex":0},"citationItems":[{"id":"BbVydael/Y8fwuXm1","uris":[""],"uri":[""],"itemData":{"id":44,"type":"article-journal","title":"Screening for pancreatic neoplasia in high-risk individuals: an EUS-based approach","container-title":"Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association","page":"606-621","volume":"2","issue":"7","source":"PubMed","abstract":"BACKGROUND & AIMS: Relatives of patients with pancreatic cancer and persons with certain inherited syndromes are at increased risk for developing pancreatic cancer. We prospectively evaluated the feasibility of screening for pancreatic neoplasia in high-risk individuals.\nMETHODS: Individuals from familial pancreatic cancer kindreds and a patient with Peutz-Jeghers syndrome underwent screening endoscopic ultrasound (EUS). If the EUS was abnormal, EUS-guided fine-needle aspiration, endoscopic retrograde cholangiopancreatography (ERCP), and spiral computed tomography (CT) were performed. Patients with abnormalities suggesting neoplasia had surgery.\nRESULTS: Thirty-eight patients were studied; 31 (mean age, 58 yr; 42% men) from kindreds with > or =3 affected with pancreatic cancer; 6 from kindreds with 2 affected relatives, 1 was a patient with Peutz-Jeghers syndrome. None had symptoms referable to the pancreas or suggestive of malignancy. Six pancreatic masses were found by EUS: 1 invasive ductal adenocarcinoma, 1 benign intraductal papillary mucinous neoplasm, 2 serous cystadenomas, and 2 nonneoplastic masses. Hence, the diagnostic yield for detecting clinically significant pancreatic neoplasms was 5.3% (2 of 38). The 1 patient with pancreatic cancer was treated and still is alive and disease-free >5 years after surgery. EUS changes similar to those associated with chronic pancreatitis were found, which were more common in patients with a history of regular alcohol intake (P = 0.02), but also occurred in patients who did not consume alcohol. Screening also led to a new diagnosis and treatment of symptomatic upper-gastrointestinal conditions in 18.4% of patients.\nCONCLUSIONS: EUS-based screening of asymptomatic high-risk individuals can detect prevalent resectable pancreatic neoplasia but false-positive diagnoses also occur.","ISSN":"1542-3565","note":"PMID: 15224285","title-short":"Screening for pancreatic neoplasia in high-risk individuals","journalAbbreviation":"Clin. Gastroenterol. Hepatol.","language":"eng","author":[{"family":"Canto","given":"Marcia Irene"},{"family":"Goggins","given":"Michael"},{"family":"Yeo","given":"Charles J."},{"family":"Griffin","given":"Constance"},{"family":"Axilbund","given":"Jennifer E."},{"family":"Brune","given":"Kieran"},{"family":"Ali","given":"Syed Z."},{"family":"Jagannath","given":"Sanjay"},{"family":"Petersen","given":"Gloria M."},{"family":"Fishman","given":"Elliot K."},{"family":"Piantadosi","given":"Steven"},{"family":"Giardiello","given":"Francis M."},{"family":"Hruban","given":"Ralph H."}],"issued":{"date-parts":[["2004",7]]}}},{"id":"BbVydael/NFPiCpG1","uris":[""],"uri":[""],"itemData":{"id":46,"type":"article-journal","title":"Screening for early pancreatic neoplasia in high-risk individuals: a prospective controlled study","container-title":"Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association","page":"766-781; quiz 665","volume":"4","issue":"6","source":"PubMed","abstract":"BACKGROUND & AIMS: Individuals with a strong family history of pancreatic cancer and persons with Peutz-Jeghers syndrome (PJS) have an increased risk for pancreatic cancer. This study screened for early pancreatic neoplasia and compared the pancreatic abnormalities in high-risk individuals and control subjects.\nMETHODS: High-risk individuals with PJS or a strong family history of pancreatic cancer were prospectively evaluated with baseline and 12-month computed tomography (CT) scan and endoscopic ultrasonography (EUS). If EUS was abnormal, EUS-fine-needle aspiration and endoscopic retrograde cholangiopancreatography (ERCP) were performed. Surgery was offered to patients with potentially neoplastic lesions. Radiologic findings and pathologic diagnoses were compared. Patients undergoing EUS and/or ERCP for benign non-pancreatic indications were concurrently enrolled as control subjects.\nRESULTS: Seventy-eight high-risk patients (72 from familial pancreatic cancer kindreds, 6 PJS) and 149 control patients were studied. To date, 8 patients with pancreatic neoplasia have been confirmed by surgery or fine-needle aspiration (10% yield of screening); 6 patients had 8 benign intraductal papillary mucinous neoplasms (IPMNs), 1 had an IPMN that progressed to invasive ductal adenocarcinoma, and 1 had pancreatic intraepithelial neoplasia. EUS and CT also diagnosed 3 patients with 5 extrapancreatic neoplasms. At EUS and ERCP abnormalities suggestive of chronic pancreatitis were more common in high-risk patients than in control subjects.\nCONCLUSIONS: Screening EUS and CT diagnosed significant asymptomatic pancreatic and extrapancreatic neoplasms in high-risk individuals. IPMN should be considered a part of the phenotype of familial pancreatic cancer. Abnormalities suggestive of chronic pancreatitis are identified more commonly at EUS and ERCP in high-risk individuals.","DOI":"10.1016/j.cgh.2006.02.005","ISSN":"1542-3565","note":"PMID: 16682259","title-short":"Screening for early pancreatic neoplasia in high-risk individuals","journalAbbreviation":"Clin. Gastroenterol. Hepatol.","language":"eng","author":[{"family":"Canto","given":"Marcia Irene"},{"family":"Goggins","given":"Michael"},{"family":"Hruban","given":"Ralph H."},{"family":"Petersen","given":"Gloria M."},{"family":"Giardiello","given":"Francis M."},{"family":"Yeo","given":"Charles"},{"family":"Fishman","given":"Elliott K."},{"family":"Brune","given":"Kieran"},{"family":"Axilbund","given":"Jennifer"},{"family":"Griffin","given":"Constance"},{"family":"Ali","given":"Syed"},{"family":"Richman","given":"Jeffrey"},{"family":"Jagannath","given":"Sanjay"},{"family":"Kantsevoy","given":"Sergey V."},{"family":"Kalloo","given":"Anthony N."}],"issued":{"date-parts":[["2006",6]]}}},{"id":"BbVydael/SGuaxGBK","uris":[""],"uri":[""],"itemData":{"id":105,"type":"article-journal","title":"Chronic pancreatitis-like changes detected by endoscopic ultrasound in subjects without signs of pancreatic disease: do these indicate age-related changes, effects of xenobiotics, or early chronic pancreatitis?","container-title":"Pancreatology: official journal of the International Association of Pancreatology (IAP) ... [et al.]","page":"597-602","volume":"10","issue":"5","source":"PubMed","abstract":"BACKGROUND/AIMS: The threshold number of endoscopic ultrasound (EUS) criteria for diagnosing chronic pancreatitis (CP) is variable. The presence of more than three abnormal ductular or parenchymal features is typically used, but the diagnostic significance of fewer EUS criteria is currently unclear. The aim of this study was to determine the prevalence of EUS features of CP in patients without pancreaticobiliary disease and to analyze the association with specific factors of interest.\nMETHODS: Over a 24-month period, 2,614 patients underwent EUS for an indication unrelated to pancreaticobiliary disease. Main outcome measurements wereunivariate and multivariate analysis between any EUS abnormality and demographic data and habits.\nRESULTS: 82 patients (16.8%) showed at least one ductular or parenchymal abnormality. 38 patients presented with only one abnormal feature, 26 patients with two, 12 patients with three, 4 patients with four, and 2 patients with five. Low-level alcohol consumption significantly increased the risk of hyperechoic parenchymal foci, main pancreatic duct (MPD) dilatation and wall hyperechogenicity. Smoking was associated with an increased risk of hyperechoic parenchymal foci. Male gender and advanced age were significantly associated with an increased risk of MPD dilatation.\nCONCLUSIONS: Long-term smoking and alcohol consumption, although at a low dose, induces CP-like changes. These abnormalities might represent either a clinically silent CP or a toxic effect of smoking and alcohol. Conversely, MPD dilation might represent a normal age-related variant or, alternatively, an effect of chronic low-level alcohol consumption. and IAP.","DOI":"10.1159/000314599","ISSN":"1424-3911","note":"PMID: 20980777","title-short":"Chronic pancreatitis-like changes detected by endoscopic ultrasound in subjects without signs of pancreatic disease","journalAbbreviation":"Pancreatology","language":"eng","author":[{"family":"Petrone","given":"Maria Chiara"},{"family":"Arcidiacono","given":"Paolo Giorgio"},{"family":"Perri","given":"Francesco"},{"family":"Carrara","given":"Silvia"},{"family":"Boemo","given":"Cinzia"},{"family":"Testoni","given":"Pier Alberto"}],"issued":{"date-parts":[["2010"]]}}},{"id":"BbVydael/LgLhAzll","uris":[""],"uri":[""],"itemData":{"id":100,"type":"article-journal","title":"Evolution of features of chronic pancreatitis during endoscopic ultrasound-based surveillance of individuals at high risk for pancreatic cancer","container-title":"Endoscopy International Open","page":"E541-E548","volume":"6","issue":"5","source":"PubMed","abstract":"Background and study aims?: During endoscopic ultrasound (EUS)-based pancreatic ductal adenocarcinoma (PDAC)-surveillance in asymptomatic individuals, features of chronic pancreatitis (CP) are often detected. Little is known about the prevalence and progression of these features. The aim of this study was to quantify these features, assess the interobserver agreement, assess possible associated factors, and assess the natural course during 3 years of follow-up.\nPatients and methods?: Two experienced endosonographers reviewed anonymized sequential EUS videos of participants in PDAC surveillance that were obtained in 2012 and 2015 for features of CP. Descriptives, agreement analyses, univariate and multivariate analyses for possible risk factors, and repeated measures analyses to assess intra-individual changes over time were performed.\nResults?: A total of 42 EUS videos of 21 participants were reviewed. Any feature of CP was present in 86?% (2012) and 81?% (2015) of participants, with a mean of 2.5 features per individual. The overall interobserver agreement was almost perfect at 83?%. No baseline factors were significantly associated with features of CP. Features did not change over time, except for hyperechoic foci without shadowing, which decreased intra-individually (β?=?-?1.6, P ?=?0.005).\nConclusions?: This blinded study shows features of CP to be highly prevalent in individuals at high risk of developing pancreatic cancer. No baseline factors were associated with presence of these features. CP features did not increase intra-individually over a 3-year period. Longer follow-up and pathological examination of pancreatic resection specimens will be essential to learn whether EUS detection and follow-up of these CP features bear clinical relevance.","DOI":"10.1055/a-0574-2396","ISSN":"2364-3722","note":"PMID: 29713680\nPMCID: PMC5909773","journalAbbreviation":"Endosc Int Open","language":"eng","author":[{"family":"Konings","given":"Ingrid C. A. W."},{"family":"Cahen","given":"Djuna L."},{"family":"Harinck","given":"Femme"},{"family":"Fockens","given":"Paul"},{"family":"Hooft","given":"Jeanin E.","non-dropping-particle":"van"},{"family":"Poley","given":"Jan-Werner"},{"family":"Bruno","given":"Marco J."}],"issued":{"date-parts":[["2018",5]]}}},{"id":"BbVydael/C5JGIjEL","uris":[""],"uri":[""],"itemData":{"id":93,"type":"article-journal","title":"Chronic pancreatitis changes in high-risk individuals for pancreatic ductal adenocarcinoma","container-title":"Gastrointestinal Endoscopy","source":"PubMed","abstract":"BACKGROUND AND AIMS: Pancreatic intraepithelial neoplasia is associated with chronic pancreatitis (CP) changes on EUS. The objective of this study was to determine whether CP changes were more common in high-risk individuals (HRIs) than in control subjects and whether these changes differed among higher-risk subsets of HRIs.\nMETHODS: HRIs and control subjects were identified from an endoscopy database. HRIs were defined as having predisposing mutations or a family history (FH) of pancreatic ductal adenocarcinoma. HRIs were classified as vHRIs who met Cancer of the Pancreas Screening (CAPS) criteria for high risk and mHRIs who did not. Multivariable logistic regression was used to adjust for confounders and CP risk factors.\nRESULTS: Sixty-five HRIs (44 vHRIs, 21 mHRIs) and 118 control subjects were included. HRIs were included for FH (25), Lynch syndrome (5), Peutz-Jeghers syndrome (2), and mutations in BRCA1/2 (26), PALB2 (3), ATM (3), and CDKN2A (1). After adjustment for relevant variables, HRIs were 16 times more likely to exhibit 3 or more CP changes than control subjects (95% confidence interval, 2.6-97.0; P?= .003). HRIs were also more likely to have hypoechoic foci (odds ratio, 8.0; 95% confidence interval, 1.9-32.9; P?= .004). vHRIs and mHRIs did not differ in frequency of 3 or more CP changes on EUS.\nCONCLUSIONS: HRIs were more likely to exhibit CP changes and hypoechoic foci on EUS compared with control subjects. HRIs with these findings may require closer surveillance. HRIs who did or did not meet CAPS criteria did not differ with regard to CP findings, supporting a more inclusive approach to screening.","DOI":"10.1016/j.gie.2018.08.029","ISSN":"1097-6779","note":"PMID: 30145314","journalAbbreviation":"Gastrointest. Endosc.","language":"eng","author":[{"family":"Thiruvengadam","given":"Sushrut S."},{"family":"Chuang","given":"Judith"},{"family":"Huang","given":"Robert"},{"family":"Girotra","given":"Mohit"},{"family":"Park","given":"Walter G."}],"issued":{"date-parts":[["2018",8,24]]}}}],"schema":""} [12,23,47–49]. The diagnostic criteria for chronic pancreatitis with EUS (Rosemont Criteria) include major criteria (hyperechoic foci with shadowing and main pancreatic duct calcification, a lobularity with honeycombing) and minor criteria (small cysts, dilated ducts ≥ 3.5 mm, irregular pancreatic ducts, dilated side branches ≥ 1 mm, hyperechoic duct walls, strands, non-shadowing hyperechoic foci, and lobularity with noncontiguous lobules) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"FLw4GiTU","properties":{"formattedCitation":"\\super [50]\\nosupersub{}","plainCitation":"[50]","noteIndex":0},"citationItems":[{"id":"BbVydael/mj7EOCBV","uris":[""],"uri":[""],"itemData":{"id":48,"type":"article-journal","title":"EUS-based criteria for the diagnosis of chronic pancreatitis: the Rosemont classification","container-title":"Gastrointestinal Endoscopy","page":"1251-1261","volume":"69","issue":"7","source":"PubMed","abstract":"BACKGROUND: EUS is increasingly used in the diagnosis of chronic pancreatitis (CP). A number of publications in this field have used different EUS terminology, features, and criteria for CP, making it difficult to reproduce their findings and apply them in clinical practice. Moreover, traditional criteria such as the Cambridge classification for CP are arguably outdated and have lost their relevance.\nOBJECTIVE: Our purpose was to establish consensus-based criteria for EUS features of CP.\nDESIGN: Consensus study.\nMAIN OUTCOME MEASUREMENTS: Thirty-two internationally recognized endosonographers anonymously voted on terminology of EUS features, rank order, and category (major vs minor criteria). Consensus was defined as greater than two thirds agreement among participants.\nRESULTS: Major criteria for CP were (1) hyperechoic foci with shadowing and main pancreatic duct (PD) calculi and (2) lobularity with honeycombing. Minor criteria for CP were cysts, dilated ducts > or =3.5 mm, irregular PD contour, dilated side branches > or =1 mm, hyperechoic duct wall, strands, nonshadowing hyperechoic foci, and lobularity with noncontiguous lobules.\nLIMITATION: Lack of broadly accepted reference standard.\nCONCLUSION: In a complex disease such as CP that has no universally accepted reference standard, an EUS-based criterion for diagnosis can be determined by expert consensus opinion and the existing body of evidence. Here we present the new \"Rosemont criteria\" for the EUS diagnosis of CP.","DOI":"10.1016/j.gie.2008.07.043","ISSN":"1097-6779","note":"PMID: 19243769","title-short":"EUS-based criteria for the diagnosis of chronic pancreatitis","journalAbbreviation":"Gastrointest. Endosc.","language":"eng","author":[{"family":"Catalano","given":"Marc F."},{"family":"Sahai","given":"Anand"},{"family":"Levy","given":"Michael"},{"family":"Romagnuolo","given":"Joseph"},{"family":"Wiersema","given":"Maurits"},{"family":"Brugge","given":"William"},{"family":"Freeman","given":"Martin"},{"family":"Yamao","given":"Kenji"},{"family":"Canto","given":"Marcia"},{"family":"Hernandez","given":"Lyndon V."}],"issued":{"date-parts":[["2009",6]]}}}],"schema":""} [50]. Chronic-pancreatitis-like parenchymal atrophy and hyperechoic foci may correspond to multifocal PanIN ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"NEl03Pxz","properties":{"formattedCitation":"\\super [51\\uc0\\u8211{}54]\\nosupersub{}","plainCitation":"[51–54]","noteIndex":0},"citationItems":[{"id":"BbVydael/qbQx1zWu","uris":[""],"uri":[""],"itemData":{"id":77,"type":"article-journal","title":"Multifocal neoplastic precursor lesions associated with lobular atrophy of the pancreas in patients having a strong family history of pancreatic cancer","container-title":"The American Journal of Surgical Pathology","page":"1067-1076","volume":"30","issue":"9","source":"PubMed","abstract":"We screened 116 patients with a strong family history of pancreatic cancer using a combination of endoscopic ultrasound and computed tomography. Ten of these patients underwent surgical resection at our institution, providing an opportunity to define the morphology of pancreatic precursor lesions in patients with a strong family history of pancreatic cancer. Eight of the 10 pancreata were available and these were entirely submitted for histologic examination. The number of pancreatic intraepithelial neoplasia (PanIN) lesions and intraductal papillary mucinous neoplasms (IPMNs) were compared with age-matched controls. Parenchymal changes were defined. Selected precursor neoplasms from 6 pancreata were microdissected and analyzed for KRAS gene mutations. PanINs were significantly more common in the 8 cases (mean of 10.7% of the duct profiles, range 1.0% to 27.3%) than in the controls (mean 1.9%, range 0% to 9.2%, P<0.01). Different KRAS gene mutations were identified in separately microdissected precursor lesions in 2 of 6 cases. IPMNs were identified in 4 of the 8 cases, including 2 pancreata each having 2 distinct IPMNs. Both the IPMNs and the PanINs, even the low-grade PanIN-1 lesions, were associated with lobular parenchymal atrophy. Some individuals with a strong family history of pancreatic cancer develop multifocal, noninvasive epithelial precursor lesions of the pancreas. PanINs and IPMNs produce obstructive lobular atrophy, and this atrophy is likely the source of the chronic pancreatitis-like changes seen in these patients. The multifocal nature of familial pancreatic neoplasia suggests that surveillance of these patients is warranted after partial pancreatectomy.","DOI":"pas.0000213265.84725.0b","ISSN":"0147-5185","note":"PMID: 16931950\nPMCID: PMC2746409","journalAbbreviation":"Am. J. Surg. Pathol.","language":"eng","author":[{"family":"Brune","given":"Kieran"},{"family":"Abe","given":"Tadayoshi"},{"family":"Canto","given":"Marcia"},{"family":"O'Malley","given":"Lauren"},{"family":"Klein","given":"Alison P."},{"family":"Maitra","given":"Anirban"},{"family":"Volkan Adsay","given":"N."},{"family":"Fishman","given":"Elliot K."},{"family":"Cameron","given":"John L."},{"family":"Yeo","given":"Charles J."},{"family":"Kern","given":"Scott E."},{"family":"Goggins","given":"Michael"},{"family":"Hruban","given":"Ralph H."}],"issued":{"date-parts":[["2006",9]]}}},{"id":"BbVydael/7DLV0dHH","uris":[""],"uri":[""],"itemData":{"id":75,"type":"article-journal","title":"Update on familial pancreatic cancer","container-title":"Advances in Surgery","page":"293-311","volume":"44","source":"PubMed","ISSN":"0065-3411","note":"PMID: 20919528\nPMCID: PMC2966038","journalAbbreviation":"Adv Surg","language":"eng","author":[{"family":"Hruban","given":"Ralph H."},{"family":"Canto","given":"Marcia I."},{"family":"Goggins","given":"Michael"},{"family":"Schulick","given":"Richard"},{"family":"Klein","given":"Alison P."}],"issued":{"date-parts":[["2010"]]}}},{"id":"BbVydael/7bWvvYpH","uris":[""],"uri":[""],"itemData":{"id":103,"type":"article-journal","title":"Multicentric pancreatic intraepithelial neoplasias (PanINs) presenting with the clinical features of chronic pancreatitis","container-title":"Journal of Hepato-Biliary-Pancreatic Surgery","page":"549-553","volume":"15","issue":"5","source":"PubMed","abstract":"A 46-year-old woman was readmitted to our hospital in August 2005 because of severe abdominal pain and nausea. Computed tomography demonstrated a huge cystic lesion in the retroperitoneal space behind the hepatoduodenal ligament and lesser peritoneal cavity. Endoscopic retrograde pancreatography revealed communication between the dilated main pancreatic duct and a pseudocyst. The condition was preoperatively diagnosed as chronic pancreatitis associated with a pseudocyst or an intraductal papillary mucinous neoplasm without mucin hypersecretion. The patient underwent a distal pancreatectomy with splenectomy. The pathologic diagnosis was multicentric pancreatic intraepithelial neoplasia (PanIN), and histological examination revealed a positive surgical margin around the remnant pancreas. Four months after the surgery, the patient underwent a total pancreatectomy. Macroscopic observation revealed diffuse fibrosis of the pancreatic parenchyma compatible with chronic pancreatitis. Histological examination revealed a constellation of noninvasive intraductal neoplasias with high-grade atypia, diffusely distributed in the small pancreatic ducts of the resected pancreas. Localized fibrosis and cystic dilation of the small ducts were detected in a lobule of exocrine glands draining into a ductule involved by PanIN lesions in the head of the pancreas. In summary, multicentric PanIN lesions are associated with lobular atrophy of the pancreatic parenchyma and chronic pancreatitis-like changes that follow. Total pancreatectomy may be recommended for patients with multicentric precursor lesions throughout the entire pancreas.","DOI":"10.1007/s00534-007-1269-7","ISSN":"0944-1166","note":"PMID: 18836812","journalAbbreviation":"J Hepatobiliary Pancreat Surg","language":"eng","author":[{"family":"Aimoto","given":"Takayuki"},{"family":"Uchida","given":"Eiji"},{"family":"Nakamura","given":"Yoshiharu"},{"family":"Matsushita","given":"Akira"},{"family":"Katsuno","given":"Akira"},{"family":"Chou","given":"Kazumitsu"},{"family":"Kawamoto","given":"Masao"},{"family":"Naito","given":"Zenya"},{"family":"Tajiri","given":"Takashi"}],"issued":{"date-parts":[["2008"]]}}},{"id":"BbVydael/0noAA4jF","uris":[""],"uri":[""],"itemData":{"id":42,"type":"article-journal","title":"Pancreatic intraepithelial neoplasia in patients with intraductal papillary mucinous neoplasms: the interest of endoscopic ultrasonography","container-title":"Pancreas","page":"1262-1266","volume":"42","issue":"8","source":"PubMed","abstract":"OBJECTIVES: Intraductal papillary mucinous neoplasms (IPMNs) and pancreatic intraepithelial neoplasia (PanIN) are both precancerous lesions. Papillary mucinous neoplasms have been described in patients with IPMN, but their relationship is still poorly understood. The aims of this study were to look for PanIN lesions in patients operated on for IPMN and to search for correlations between endoscopic ultrasonography(EUS) features and pathologic findings.\nMETHODS: Endoscopic ultrasonography was preoperatively performed in all patients with IPMN consecutively operated on in our center. Endoscopic ultrasonography features were prospectively compared with pathologic data from surgical specimen.\nRESULTS: Forty patients underwent resection for benign (52.5%) or malignant (47.5%) IPMN. Pancreatic intraepithelial neoplasia lesions were observed in 78% of cases (PanIN-3 in 19% of patients). PanIN-3 lesions were observed in 11% and 26% of patients with benign and malignant IPMN, respectively. Endoscopic ultrasonography changes(microcysts and/or hyperechoic foci) corresponded to PanIN lesions in 83% of cases. Endoscopic ultrasonography detected 69% of patients with PanIN lesions and 57% of those with panIN-3 lesions.\nCONCLUSIONS: Pancreatic intraepithelial neoplasia lesions are very frequently associated with IPMN, and 19% of patients with IPMN had PanIN-3 lesions. In two thirds of patients, EUS can detect minimal changes in the pancreas corresponding to PanIN lesions.","DOI":"10.1097/01.mpa.0000437639.38383.41","ISSN":"1536-4828","note":"PMID: 24152960","title-short":"Pancreatic intraepithelial neoplasia in patients with intraductal papillary mucinous neoplasms","journalAbbreviation":"Pancreas","language":"eng","author":[{"family":"Maire","given":"Frédérique"},{"family":"Couvelard","given":"Anne"},{"family":"Palazzo","given":"Laurent"},{"family":"Aubert","given":"Alain"},{"family":"Vullierme","given":"Marie-Pierre"},{"family":"Rebours","given":"Vinciane"},{"family":"Hammel","given":"Pascal"},{"family":"Sauvanet","given":"Alain"},{"family":"Levy","given":"Philippe"},{"family":"Ruszniewski","given":"Philippe"}],"issued":{"date-parts":[["2013",11]]}}}],"schema":""} [51–54]. Brune et al ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"f4ZQSIDh","properties":{"formattedCitation":"\\super [51]\\nosupersub{}","plainCitation":"[51]","noteIndex":0},"citationItems":[{"id":"BbVydael/qbQx1zWu","uris":[""],"uri":[""],"itemData":{"id":77,"type":"article-journal","title":"Multifocal neoplastic precursor lesions associated with lobular atrophy of the pancreas in patients having a strong family history of pancreatic cancer","container-title":"The American Journal of Surgical Pathology","page":"1067-1076","volume":"30","issue":"9","source":"PubMed","abstract":"We screened 116 patients with a strong family history of pancreatic cancer using a combination of endoscopic ultrasound and computed tomography. Ten of these patients underwent surgical resection at our institution, providing an opportunity to define the morphology of pancreatic precursor lesions in patients with a strong family history of pancreatic cancer. Eight of the 10 pancreata were available and these were entirely submitted for histologic examination. The number of pancreatic intraepithelial neoplasia (PanIN) lesions and intraductal papillary mucinous neoplasms (IPMNs) were compared with age-matched controls. Parenchymal changes were defined. Selected precursor neoplasms from 6 pancreata were microdissected and analyzed for KRAS gene mutations. PanINs were significantly more common in the 8 cases (mean of 10.7% of the duct profiles, range 1.0% to 27.3%) than in the controls (mean 1.9%, range 0% to 9.2%, P<0.01). Different KRAS gene mutations were identified in separately microdissected precursor lesions in 2 of 6 cases. IPMNs were identified in 4 of the 8 cases, including 2 pancreata each having 2 distinct IPMNs. Both the IPMNs and the PanINs, even the low-grade PanIN-1 lesions, were associated with lobular parenchymal atrophy. Some individuals with a strong family history of pancreatic cancer develop multifocal, noninvasive epithelial precursor lesions of the pancreas. PanINs and IPMNs produce obstructive lobular atrophy, and this atrophy is likely the source of the chronic pancreatitis-like changes seen in these patients. The multifocal nature of familial pancreatic neoplasia suggests that surveillance of these patients is warranted after partial pancreatectomy.","DOI":"pas.0000213265.84725.0b","ISSN":"0147-5185","note":"PMID: 16931950\nPMCID: PMC2746409","journalAbbreviation":"Am. J. Surg. Pathol.","language":"eng","author":[{"family":"Brune","given":"Kieran"},{"family":"Abe","given":"Tadayoshi"},{"family":"Canto","given":"Marcia"},{"family":"O'Malley","given":"Lauren"},{"family":"Klein","given":"Alison P."},{"family":"Maitra","given":"Anirban"},{"family":"Volkan Adsay","given":"N."},{"family":"Fishman","given":"Elliot K."},{"family":"Cameron","given":"John L."},{"family":"Yeo","given":"Charles J."},{"family":"Kern","given":"Scott E."},{"family":"Goggins","given":"Michael"},{"family":"Hruban","given":"Ralph H."}],"issued":{"date-parts":[["2006",9]]}}}],"schema":""} [51] reported a significant correlation between CPis on EUS and percentage of PanIN lesions on surgical specimens. The supposed explanation is that multifocal PanIN lesions produce obstructive lobular atrophy, which is probably the source of CPis ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"zf39be9V","properties":{"formattedCitation":"\\super [53]\\nosupersub{}","plainCitation":"[53]","noteIndex":0},"citationItems":[{"id":"BbVydael/7bWvvYpH","uris":[""],"uri":[""],"itemData":{"id":103,"type":"article-journal","title":"Multicentric pancreatic intraepithelial neoplasias (PanINs) presenting with the clinical features of chronic pancreatitis","container-title":"Journal of Hepato-Biliary-Pancreatic Surgery","page":"549-553","volume":"15","issue":"5","source":"PubMed","abstract":"A 46-year-old woman was readmitted to our hospital in August 2005 because of severe abdominal pain and nausea. Computed tomography demonstrated a huge cystic lesion in the retroperitoneal space behind the hepatoduodenal ligament and lesser peritoneal cavity. Endoscopic retrograde pancreatography revealed communication between the dilated main pancreatic duct and a pseudocyst. The condition was preoperatively diagnosed as chronic pancreatitis associated with a pseudocyst or an intraductal papillary mucinous neoplasm without mucin hypersecretion. The patient underwent a distal pancreatectomy with splenectomy. The pathologic diagnosis was multicentric pancreatic intraepithelial neoplasia (PanIN), and histological examination revealed a positive surgical margin around the remnant pancreas. Four months after the surgery, the patient underwent a total pancreatectomy. Macroscopic observation revealed diffuse fibrosis of the pancreatic parenchyma compatible with chronic pancreatitis. Histological examination revealed a constellation of noninvasive intraductal neoplasias with high-grade atypia, diffusely distributed in the small pancreatic ducts of the resected pancreas. Localized fibrosis and cystic dilation of the small ducts were detected in a lobule of exocrine glands draining into a ductule involved by PanIN lesions in the head of the pancreas. In summary, multicentric PanIN lesions are associated with lobular atrophy of the pancreatic parenchyma and chronic pancreatitis-like changes that follow. Total pancreatectomy may be recommended for patients with multicentric precursor lesions throughout the entire pancreas.","DOI":"10.1007/s00534-007-1269-7","ISSN":"0944-1166","note":"PMID: 18836812","journalAbbreviation":"J Hepatobiliary Pancreat Surg","language":"eng","author":[{"family":"Aimoto","given":"Takayuki"},{"family":"Uchida","given":"Eiji"},{"family":"Nakamura","given":"Yoshiharu"},{"family":"Matsushita","given":"Akira"},{"family":"Katsuno","given":"Akira"},{"family":"Chou","given":"Kazumitsu"},{"family":"Kawamoto","given":"Masao"},{"family":"Naito","given":"Zenya"},{"family":"Tajiri","given":"Takashi"}],"issued":{"date-parts":[["2008"]]}}}],"schema":""} [53]. Features of chronic pancreatitis during EUS-based surveillance of HRI are easily seen with good interobserver agreement ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"zKSEvpAY","properties":{"formattedCitation":"\\super [48]\\nosupersub{}","plainCitation":"[48]","noteIndex":0},"citationItems":[{"id":"BbVydael/LgLhAzll","uris":[""],"uri":[""],"itemData":{"id":100,"type":"article-journal","title":"Evolution of features of chronic pancreatitis during endoscopic ultrasound-based surveillance of individuals at high risk for pancreatic cancer","container-title":"Endoscopy International Open","page":"E541-E548","volume":"6","issue":"5","source":"PubMed","abstract":"Background and study aims?: During endoscopic ultrasound (EUS)-based pancreatic ductal adenocarcinoma (PDAC)-surveillance in asymptomatic individuals, features of chronic pancreatitis (CP) are often detected. Little is known about the prevalence and progression of these features. The aim of this study was to quantify these features, assess the interobserver agreement, assess possible associated factors, and assess the natural course during 3 years of follow-up.\nPatients and methods?: Two experienced endosonographers reviewed anonymized sequential EUS videos of participants in PDAC surveillance that were obtained in 2012 and 2015 for features of CP. Descriptives, agreement analyses, univariate and multivariate analyses for possible risk factors, and repeated measures analyses to assess intra-individual changes over time were performed.\nResults?: A total of 42 EUS videos of 21 participants were reviewed. Any feature of CP was present in 86?% (2012) and 81?% (2015) of participants, with a mean of 2.5 features per individual. The overall interobserver agreement was almost perfect at 83?%. No baseline factors were significantly associated with features of CP. Features did not change over time, except for hyperechoic foci without shadowing, which decreased intra-individually (β?=?-?1.6, P ?=?0.005).\nConclusions?: This blinded study shows features of CP to be highly prevalent in individuals at high risk of developing pancreatic cancer. No baseline factors were associated with presence of these features. CP features did not increase intra-individually over a 3-year period. Longer follow-up and pathological examination of pancreatic resection specimens will be essential to learn whether EUS detection and follow-up of these CP features bear clinical relevance.","DOI":"10.1055/a-0574-2396","ISSN":"2364-3722","note":"PMID: 29713680\nPMCID: PMC5909773","journalAbbreviation":"Endosc Int Open","language":"eng","author":[{"family":"Konings","given":"Ingrid C. A. W."},{"family":"Cahen","given":"Djuna L."},{"family":"Harinck","given":"Femme"},{"family":"Fockens","given":"Paul"},{"family":"Hooft","given":"Jeanin E.","non-dropping-particle":"van"},{"family":"Poley","given":"Jan-Werner"},{"family":"Bruno","given":"Marco J."}],"issued":{"date-parts":[["2018",5]]}}}],"schema":""} [48]. One study showed that CPis generally have no or little progression over time, although the follow-up period was limited (3 years) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"3AIlFqeC","properties":{"formattedCitation":"\\super [48]\\nosupersub{}","plainCitation":"[48]","noteIndex":0},"citationItems":[{"id":"BbVydael/LgLhAzll","uris":[""],"uri":[""],"itemData":{"id":100,"type":"article-journal","title":"Evolution of features of chronic pancreatitis during endoscopic ultrasound-based surveillance of individuals at high risk for pancreatic cancer","container-title":"Endoscopy International Open","page":"E541-E548","volume":"6","issue":"5","source":"PubMed","abstract":"Background and study aims?: During endoscopic ultrasound (EUS)-based pancreatic ductal adenocarcinoma (PDAC)-surveillance in asymptomatic individuals, features of chronic pancreatitis (CP) are often detected. Little is known about the prevalence and progression of these features. The aim of this study was to quantify these features, assess the interobserver agreement, assess possible associated factors, and assess the natural course during 3 years of follow-up.\nPatients and methods?: Two experienced endosonographers reviewed anonymized sequential EUS videos of participants in PDAC surveillance that were obtained in 2012 and 2015 for features of CP. Descriptives, agreement analyses, univariate and multivariate analyses for possible risk factors, and repeated measures analyses to assess intra-individual changes over time were performed.\nResults?: A total of 42 EUS videos of 21 participants were reviewed. Any feature of CP was present in 86?% (2012) and 81?% (2015) of participants, with a mean of 2.5 features per individual. The overall interobserver agreement was almost perfect at 83?%. No baseline factors were significantly associated with features of CP. Features did not change over time, except for hyperechoic foci without shadowing, which decreased intra-individually (β?=?-?1.6, P ?=?0.005).\nConclusions?: This blinded study shows features of CP to be highly prevalent in individuals at high risk of developing pancreatic cancer. No baseline factors were associated with presence of these features. CP features did not increase intra-individually over a 3-year period. Longer follow-up and pathological examination of pancreatic resection specimens will be essential to learn whether EUS detection and follow-up of these CP features bear clinical relevance.","DOI":"10.1055/a-0574-2396","ISSN":"2364-3722","note":"PMID: 29713680\nPMCID: PMC5909773","journalAbbreviation":"Endosc Int Open","language":"eng","author":[{"family":"Konings","given":"Ingrid C. A. W."},{"family":"Cahen","given":"Djuna L."},{"family":"Harinck","given":"Femme"},{"family":"Fockens","given":"Paul"},{"family":"Hooft","given":"Jeanin E.","non-dropping-particle":"van"},{"family":"Poley","given":"Jan-Werner"},{"family":"Bruno","given":"Marco J."}],"issued":{"date-parts":[["2018",5]]}}}],"schema":""} [48]. A fatty pancreas has also been reported to be a risk factor for PC and should be noted on the EUS report ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"ds29go0d","properties":{"formattedCitation":"\\super [55]\\nosupersub{}","plainCitation":"[55]","noteIndex":0},"citationItems":[{"id":"BbVydael/D0A0D2zM","uris":[""],"uri":[""],"itemData":{"id":90,"type":"article-journal","title":"Non-alcoholic fatty pancreas disease as a risk factor for pancreatic cancer based on endoscopic ultrasound examination among pancreatic cancer patients: A single-center experience","container-title":"JGH open: an open access journal of gastroenterology and hepatology","page":"4-7","volume":"2","issue":"1","source":"PubMed","abstract":"Background and Aim: Non-alcoholic fatty pancreas disease (NAFPD) is a disease that ranges from simple steatosis and can further lead to chronic pancreatitis and possible pancreatic cancer development. Its exact pathogenesis and impact on clinical practice are still largely unknown. Pancreatic cancer is still the most lethal malignancy in the world. Studies about the relationship between NAFPD and pancreatic cancer are still lacking. This study aims to find the possible role of endoscopic ultrasound (EUS) examination as a screening tool in NAFPD patients based on EUS examination among pancreatic cancer patients.\nMethods: EUS hospital data were collected within a 2-year period, and all patients who underwent EUS procedures were analyzed. Pancreatic malignancy was diagnosed based on imaging and tumor markers and cytopathology using the endoscopic ultrasound fine needle aspiration (EUS-FNA) procedure. Patients with pre-existing pancreatic diseases, significant alcohol consumption, or other primary cancer with metastasis to the pancreas were excluded. Statistical analysis was performed using SPSS version 23.0.\nResults: In total, 162 patients (75 females and 87 males) were recruited for database analysis.^ Pancreatic malignancy was found in 43 (26.5%) patients, whereas fatty pancreas was found in 53 (32.7%) patients, and this was commonly found among pancreatic cancer patients.^ Based on logistic regression analysis, factors such as age, gender, diabetes, and chronic pancreatitis were not found to be significant risk factors for pancreatic malignancy where fatty pancreas is the only significant risk factor for pancreatic cancer (odds ratio: 18.027 [95% CI: 7.288-44.588]).\nConclusion: Prevalence of NAFPD among pancreatic cancer patients is high. Future studies can be conducted to show whether EUS can be considered a screening tool for the early detection of pancreatic malignancy in NAFPD patients; a cohort prospective study might also be needed to show clear causality between fatty pancreas and pancreatic cancer.","DOI":"10.1002/jgh3.12032","ISSN":"2397-9070","note":"PMID: 30483555\nPMCID: PMC6207022","title-short":"Non-alcoholic fatty pancreas disease as a risk factor for pancreatic cancer based on endoscopic ultrasound examination among pancreatic cancer patients","journalAbbreviation":"JGH Open","language":"eng","author":[{"family":"Lesmana","given":"Cosmas R. A."},{"family":"Gani","given":"Rino A."},{"family":"Lesmana","given":"Laurentius A."}],"issued":{"date-parts":[["2018",2]]}}}],"schema":""} [55].Finally, EUS can identify solid pancreatic lesions in up to 20% of HRI during follow-up. These solid tumours are generally PC but may also be PanIN with HGD or neuroendocrine tumours ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"TwlIzcI5","properties":{"formattedCitation":"\\super [10,11,15,26,31,32,40]\\nosupersub{}","plainCitation":"[10,11,15,26,31,32,40]","noteIndex":0},"citationItems":[{"id":"BbVydael/jiIYxhxp","uris":[""],"uri":[""],"itemData":{"id":65,"type":"article-journal","title":"PanGen-Fam: Spanish registry of hereditary pancreatic cancer","container-title":"European Journal of Cancer (Oxford, England: 1990)","page":"1911-1917","volume":"51","issue":"14","source":"PubMed","abstract":"PURPOSE: To describe the organisation of the registry and the preliminary results in terms of characteristics of high-risk pancreatic ductal adenocarcinoma (PDAC) families recruited to date and findings of the screening programme. To compare early onset sporadic cases (?50 years), sporadic cases (>50 years) and cases with family history of cancer, for PDAC possible risk factors.\nMETHODS/PATIENTS: Families with hereditary cancer syndromes predisposing to PDAC were recruited from two main sources: Spanish hospitals participating in PanGenEU, a pan-European multicentre case-control study, and their genetic counseling unit. Individuals at high-risk of PDAC were enrolled into a screening programme, consisting of Endoscopic ultrasound, computerised tomography, magnetic resonance imaging. Genetic testing of candidate genes was offered according to each patient's risk.\nRESULTS: Among 577 consecutive PDAC cases, recruited via PanGenEU, 36 (6%) had ?2 first-degree relative with PDAC: Familial pancreatic cancer (FPC). So far PanGen-Fam has recruited 42 high-risk PDAC families; 25 (60%) had FPC. Five index cases with cancer were positive for BRCA2 and one for BRCA1 germline mutations. In the second year of prospective PDAC screening, one neuroendocrine tumour and a high-grade dysplasia lesion suspicious of carcinoma were diagnosed among 41 high-risk individuals. Furthermore EUS detected chronic-pancreatitis-like parenchymal changes in 15 patients.\nCONCLUDING STATEMENT: The identification and recruitment of PDAC high-risk families into the PanGen-Fam registry provides an opportunity to detect early onset cancer and precursor pancreatic cancer lesions at a potentially curative stage and to increase the knowledge of the natural history of the disease.","DOI":"10.1016/j.ejca.2015.07.004","ISSN":"1879-0852","note":"PMID: 26212471","title-short":"PanGen-Fam","journalAbbreviation":"Eur. J. Cancer","language":"eng","author":[{"family":"Mocci","given":"E."},{"family":"Guillen-Ponce","given":"C."},{"family":"Earl","given":"J."},{"family":"Marquez","given":"M."},{"family":"Solera","given":"J."},{"family":"Salazar-López","given":"M.-T."},{"family":"Calcedo-Arnáiz","given":"C."},{"family":"Vázquez-Sequeiros","given":"E."},{"family":"Montans","given":"J."},{"family":"Mu?oz-Beltrán","given":"M."},{"family":"Vicente-Bártulos","given":"A."},{"family":"González-Gordaliza","given":"C."},{"family":"Sanjuanbenito","given":"A."},{"family":"Guerrero","given":"C."},{"family":"Mendía","given":"E."},{"family":"Lisa","given":"E."},{"family":"Lobo","given":"E."},{"family":"Martínez","given":"J. C."},{"family":"Real","given":"F. X."},{"family":"Malats","given":"N."},{"family":"Carrato","given":"A."}],"issued":{"date-parts":[["2015",9]]}}},{"id":"BbVydael/iMJ7y1A2","uris":[""],"uri":[""],"itemData":{"id":33,"type":"article-journal","title":"Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma: a patient-level meta-analysis and proposition of the Beaujon score","container-title":"United European Gastroenterology Journal","page":"205064061882491","source":"Crossref","DOI":"10.1177/2050640618824910","ISSN":"2050-6406, 2050-6414","title-short":"Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma","language":"en","author":[{"family":"Mestier","given":"Louis","non-dropping-particle":"de"},{"family":"Muller","given":"Marie"},{"family":"Cros","given":"Jér?me"},{"family":"Vullierme","given":"Marie-Pierre"},{"family":"Vernerey","given":"Dewi"},{"family":"Maire","given":"Frédérique"},{"family":"Dokmak","given":"Safi"},{"family":"Rebours","given":"Vinciane"},{"family":"Sauvanet","given":"Alain"},{"family":"Lévy","given":"Philippe"},{"family":"Hammel","given":"Pascal"}],"issued":{"date-parts":[["2019",1,12]]}}},{"id":"BbVydael/TT8LQAKI","uris":[""],"uri":[""],"itemData":{"id":79,"type":"article-journal","title":"Five years of prospective screening of high-risk individuals from families with familial pancreatic cancer","container-title":"Gut","page":"1410-1418","volume":"58","issue":"10","source":"PubMed","abstract":"OBJECTIVE: Familial pancreatic cancer (FPC) accounts for approximately 3% of all pancreatic cancer (PC) cases. It has been suggested that high-risk individuals (HRIs) should be offered a screening programme.\nAIM: To evaluate the diagnostic yield of a prospective screening programme in HRIs from families with FPC over a period of 5 years.\nMETHODS: HRIs of families with FPC of the National German Familial Pancreatic Cancer Registry (FaPaCa) were counselled and enrolled in a prospective, board-approved PC screening programme. Screening included clinical examination, laboratory tests, endoscopic ultrasound (EUS) and MRI with magnetic resonance cholangiopancreaticography (MRCP) and MR angiography.\nRESULTS: Between June 2002 and December 2007, 76 HRIs of families with FPC took part in the screening programme with a total of 182 examination visits. Twenty-eight patients revealed abnormalities in EUS (n = 25) and/or MR/MRCP (n = 12). In 7 patients fine needle aspiration cytology was performed. Operative pancreatic explorations were performed in 7 individuals, resulting in limited resections in 6 cases. Histopathological examination of the resected specimens showed serous oligocystic adenomas (n = 3), pancreatic intraepithelial neoplasia 1 (PanIN1) lesions with lobular fibrosis (n = 1), PanIN2 lesions (n = 1) and PanIN1 lesion plus a gastric type intraductal papillary mucinous neoplasm (IPMN) (n = 1).\nCONCLUSIONS: In FPC an EUS/MR/MRCP-based screening programme leads to the detection of potential precursor lesions of PC. However, the yield of an extensive screening programme is low, especially since the tumourigenic value of low grade PanIN lesions is not yet defined. Taking into account the enormous psychological stress for the tested individual and the high costs, a general PC screening in HRIs is not justified.","DOI":"10.1136/gut.2008.171611","ISSN":"1468-3288","note":"PMID: 19470496","journalAbbreviation":"Gut","language":"eng","author":[{"family":"Langer","given":"P."},{"family":"Kann","given":"P. H."},{"family":"Fendrich","given":"V."},{"family":"Habbe","given":"N."},{"family":"Schneider","given":"M."},{"family":"Sina","given":"M."},{"family":"Slater","given":"E. P."},{"family":"Heverhagen","given":"J. T."},{"family":"Gress","given":"T. M."},{"family":"Rothmund","given":"M."},{"family":"Bartsch","given":"D. K."}],"issued":{"date-parts":[["2009",10]]}}},{"id":"BbVydael/w0k4vP4h","uris":[""],"uri":[""],"itemData":{"id":113,"type":"article-journal","title":"Methods and outcomes of screening for pancreatic adenocarcinoma in high-risk individuals","container-title":"World Journal of Gastrointestinal Endoscopy","page":"833-842","volume":"7","issue":"9","source":"PubMed","abstract":"Pancreatic ductal adenocarcinoma (PDAC) is a lethal neoplasia, for which secondary prevention (i.e., screening) is advisable for high-risk individuals with \"familiar pancreatic cancer\" and with other specific genetic syndromes (Peutz-Jeghers, p16, BRCA2, PALB and mismatch repair gene mutation carriers). There is limited evidence regarding the accuracy of screening tests, their acceptability, costs and availability, and agreement on whom to treat. Successful target of screening are small resectable PDAC, intraductal papillary mucinous neoplasms with high-grade dysplasia and advanced pancreatic intraepithelial neoplasia. Both magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS) are employed for screening, and the overall yield for pre-malignant or malignant pancreatic lesions is of about 20% with EUS and 14% with MRI/magnetic resonance colangiopancreatography. EUS performs better for solid and MRI for cystic lesions. However, only 2% of these detected lesions can be considered a successful target, and there are insufficient data demonstrating that resection of benign or low grade lesions improves survival. Many patients in the published studies therefore seemed to have received an overtreatment by undergoing surgery. It is crucial to better stratify the risk of malignancy individually, and to better define optimal screening intervals and methods either with computerized tools or molecular biomarkers, possibly in large multicentre studies. At the moment, screening should be carefully performed within research protocols at experienced centres, offering involved individuals medical and psychological advice.","DOI":"10.4253/wjge.v7.i9.833","ISSN":"1948-5190","note":"PMID: 26240684\nPMCID: PMC4515417","journalAbbreviation":"World J Gastrointest Endosc","language":"eng","author":[{"family":"Capurso","given":"Gabriele"},{"family":"Signoretti","given":"Marianna"},{"family":"Valente","given":"Roberto"},{"family":"Arnelo","given":"Urban"},{"family":"Lohr","given":"Matthias"},{"family":"Poley","given":"Jan-Werner"},{"family":"Delle Fave","given":"Gianfranco"},{"family":"Del Chiaro","given":"Marco"}],"issued":{"date-parts":[["2015",7,25]]}}},{"id":"BbVydael/Sm6GTEmo","uris":[""],"uri":[""],"itemData":{"id":70,"type":"article-journal","title":"Benefit of Surveillance for Pancreatic Cancer in High-Risk Individuals: Outcome of Long-Term Prospective Follow-Up Studies From Three European Expert Centers","container-title":"Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology","page":"2010-2019","volume":"34","issue":"17","source":"PubMed","abstract":"PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis. Hereditary factors play a role in the development of PDAC in 3% to 5% of all patients. Surveillance of high-risk groups, may facilitate detection of PDAC at an early stage. The aim of this study was to assess whether surveillance aids detection of early-stage PDAC or precursor lesions (PRLs) and improves the prognosis.\nPATIENTS AND METHODS: Screening outcomes were collected from three European centers that conduct prospective screening in high-risk groups including families with clustering of PDAC (familial pancreatic cancer [FPC]) or families with a gene defect that predisposes to PDAC. The surveillance program consisted of annual magnetic resonance imaging, magnetic resonance cholangiopancreatography, and/or endoscopic ultrasound.\nRESULTS: Four hundred eleven asymptomatic individuals participated in the surveillance programs, including 178 CDKN2A mutation carriers, 214 individuals with FPC, and 19 BRCA1/2 or PALB2 mutation carriers. PDAC was detected in 13 (7.3%) of 178 CDKN2A mutation carriers. The resection rate was 75%, and the 5-year survival rate was 24%. Two CDKN2A mutation carriers (1%) underwent surgical resection for low-risk PRL. Two individuals (0.9%) in the FPC cohort had a pancreatic tumor, including one advanced PDAC and one early grade 2 neuroendocrine tumor. Thirteen individuals with FPC (6.1%) underwent surgical resection for a suspected PRL, but only four (1.9%) had high-risk lesions (ie, high-grade intraductal papillary mucinous neoplasms or grade 3 pancreatic intraepithelial neoplasms). One BRCA2 mutation carrier was found to have PDAC, and another BRCA2 mutation carrier and a PALB2 mutation carrier underwent surgery and were found to have low-risk PRL. No serious complications occurred as consequence of the program.\nCONCLUSION: Surveillance of CDNK2A mutation carriers is relatively successful, detecting most PDACs at a resectable stage. The benefit of surveillance in families with FPC is less evident.","DOI":"10.1200/JCO.2015.64.0730","ISSN":"1527-7755","note":"PMID: 27114589","title-short":"Benefit of Surveillance for Pancreatic Cancer in High-Risk Individuals","journalAbbreviation":"J. Clin. Oncol.","language":"eng","author":[{"family":"Vasen","given":"Hans"},{"family":"Ibrahim","given":"Isaura"},{"family":"Ponce","given":"Carmen Guillen"},{"family":"Slater","given":"Emily P."},{"family":"Matth?i","given":"Elvira"},{"family":"Carrato","given":"Alfredo"},{"family":"Earl","given":"Julie"},{"family":"Robbers","given":"Kristin"},{"family":"Mil","given":"Anneke M.","non-dropping-particle":"van"},{"family":"Potjer","given":"Thomas"},{"family":"Bonsing","given":"Bert A."},{"family":"Vos Tot Nederveen Cappel","given":"Wouter H.","non-dropping-particle":"de"},{"family":"Bergman","given":"Wilma"},{"family":"Wasser","given":"Martin"},{"family":"Morreau","given":"Hans"},{"family":"Kl?ppel","given":"Günter"},{"family":"Schicker","given":"Christoph"},{"family":"Steinkamp","given":"Martin"},{"family":"Figiel","given":"Jens"},{"family":"Esposito","given":"Irene"},{"family":"Mocci","given":"Evelina"},{"family":"Vazquez-Sequeiros","given":"Enrique"},{"family":"Sanjuanbenito","given":"Alfonso"},{"family":"Mu?oz-Beltran","given":"Maria"},{"family":"Montans","given":"José"},{"family":"Langer","given":"Peter"},{"family":"Fendrich","given":"Volker"},{"family":"Bartsch","given":"Detlef K."}],"issued":{"date-parts":[["2016"]],"season":"10"}}},{"id":"BbVydael/S8JLwcaf","uris":[""],"uri":[""],"itemData":{"id":63,"type":"article-journal","title":"Screening for pancreatic cancer in a high-risk cohort: an eight-year experience","container-title":"Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract","page":"771-783","volume":"16","issue":"4","source":"PubMed","abstract":"BACKGROUND: Pancreatic adenocarcinoma is the fourth leading cause of cancer death.\nMETHODS: A prospective cohort study was undertaken between 2003 and 2011 at a tertiary care centre in Toronto, Canada. Two hundred and sixty-two subjects were enrolled based on an elevated estimated lifetime risk for pancreatic cancer due to known genetic mutations and/or cancer family history. Subjects underwent annual magnetic resonance imaging, followed by additional investigations if abnormal findings were detected. Evidence of malignancy or suspicious macroscopic abnormalities prompted referral for surgical intervention.\nRESULTS: Average length of follow-up was 4.2 years, during which 84/262 (32%) subjects demonstrated pancreatic abnormalities. Three participants developed pancreatic adenocarcinoma (one 1.5-cm tumor was resected but recurred, while the other two subjects developed metastatic cancer), and a fourth participant developed a pancreatic neuroendocrine tumor that was resected. Fifteen subjects had radiologic evidence of branch-duct intraductal papillary mucinous neoplasms, of which two underwent surgical resection. Sixty-five subjects had simple pancreatic cysts that have remained stable.\nCONCLUSION: Magnetic resonance imaging can detect small pancreatic tumors and cystic lesions, but further improvement in sensitivity is needed. An understanding of the natural history of pre-invasive lesions in members of high-risk families is necessary for developing a more effective screening program.","DOI":"10.1007/s11605-011-1781-6","ISSN":"1873-4626","note":"PMID: 22127781","title-short":"Screening for pancreatic cancer in a high-risk cohort","journalAbbreviation":"J. Gastrointest. Surg.","language":"eng","author":[{"family":"Al-Sukhni","given":"Wigdan"},{"family":"Borgida","given":"Ayelet"},{"family":"Rothenmund","given":"Heidi"},{"family":"Holter","given":"Spring"},{"family":"Semotiuk","given":"Kara"},{"family":"Grant","given":"Robert"},{"family":"Wilson","given":"Stephanie"},{"family":"Moore","given":"Malcolm"},{"family":"Narod","given":"Steven"},{"family":"Jhaveri","given":"Kartik"},{"family":"Haider","given":"Masoom A."},{"family":"Gallinger","given":"Steven"}],"issued":{"date-parts":[["2012",4]]}}},{"id":"BbVydael/Y03HYTFt","uris":[""],"uri":[""],"itemData":{"id":136,"type":"article-journal","title":"German national case collection for familial pancreatic cancer (FaPaCa): ten years experience","container-title":"Familial Cancer","page":"323-330","volume":"10","issue":"2","source":"PubMed","abstract":"Familial pancreatic cancer (FPC) is a rare hereditary tumor syndrome. The 10-years experience of the national case collection for familial pancreatic cancer of Germany (FaPaCa) is reported. Since 1999 FaPaCa has collected families with at least two first-degree relatives with confirmed pancreatic cancer (PC), who did not fulfill the criteria of other hereditary tumor syndromes. Histopathological verification of tumor diagnoses, and genetic counseling were prerequisites for enrollment of families in FaPaCa. 94 of 452 evaluated families fulfilled the criteria for partaking in FaPaCa. PC represented the sole tumor entity in 38 (40%) families. In 56 families additional tumor types occurred, including breast cancer (n?=?28), colon cancer (n?=?20) and lung cancer (n?=?11). In 70 (74%) families the pattern of inheritance was consistent with an autosomal dominant trait. Compared to the preceding generation, a younger age of onset was observed in the offspring of PC patients (median: 57 vs. 69?years), indicating anticipation. Mutation analyses of BRCA2, PALB2, CDKN2a, RNASEL, STK11, NOD2, CHEK2 and PALLD, revealed deleterious causative germline mutations of BRCA2 and PALB2 in 2 of 70 (3%) and 2 of 41 (4.9%) German FPC families, respectively. Prospective PC screening with EUS, MRI and MRCP detected precancerous lesions (IPMN, multifocal PanIN2/3) or carcinoma in 5.5% (4 of 72) to 12.5% (9 of 72) of individuals at risk, depending on histological verification. Appropriate inclusion of families at high risk for PC in registries, such as FaPaCa, provides a unique and excellent tool to gain clinical and genetic knowledge of FPC. Focused research projects can be conducted most efficiently, when data of different FPC registries are combined.","DOI":"10.1007/s10689-010-9414-x","ISSN":"1573-7292","note":"PMID: 21207249","title-short":"German national case collection for familial pancreatic cancer (FaPaCa)","journalAbbreviation":"Fam. Cancer","language":"eng","author":[{"family":"Schneider","given":"Ralph"},{"family":"Slater","given":"Emily P."},{"family":"Sina","given":"Mercede"},{"family":"Habbe","given":"Nils"},{"family":"Fendrich","given":"Volker"},{"family":"Matth?i","given":"Elvira"},{"family":"Langer","given":"Peter"},{"family":"Bartsch","given":"Detlef K."}],"issued":{"date-parts":[["2011",6]]}}}],"schema":""} [10,11,15,26,31,32,40]. In published studies, 14/53 (26%) of operated significant lesions (for which MRI and EUS data were available) were only seen on EUS (Table 1) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"ChRjUK5O","properties":{"formattedCitation":"\\super [12,15,23,27,31]\\nosupersub{}","plainCitation":"[12,15,23,27,31]","noteIndex":0},"citationItems":[{"id":"BbVydael/Y8fwuXm1","uris":[""],"uri":[""],"itemData":{"id":44,"type":"article-journal","title":"Screening for pancreatic neoplasia in high-risk individuals: an EUS-based approach","container-title":"Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association","page":"606-621","volume":"2","issue":"7","source":"PubMed","abstract":"BACKGROUND & AIMS: Relatives of patients with pancreatic cancer and persons with certain inherited syndromes are at increased risk for developing pancreatic cancer. We prospectively evaluated the feasibility of screening for pancreatic neoplasia in high-risk individuals.\nMETHODS: Individuals from familial pancreatic cancer kindreds and a patient with Peutz-Jeghers syndrome underwent screening endoscopic ultrasound (EUS). If the EUS was abnormal, EUS-guided fine-needle aspiration, endoscopic retrograde cholangiopancreatography (ERCP), and spiral computed tomography (CT) were performed. Patients with abnormalities suggesting neoplasia had surgery.\nRESULTS: Thirty-eight patients were studied; 31 (mean age, 58 yr; 42% men) from kindreds with > or =3 affected with pancreatic cancer; 6 from kindreds with 2 affected relatives, 1 was a patient with Peutz-Jeghers syndrome. None had symptoms referable to the pancreas or suggestive of malignancy. Six pancreatic masses were found by EUS: 1 invasive ductal adenocarcinoma, 1 benign intraductal papillary mucinous neoplasm, 2 serous cystadenomas, and 2 nonneoplastic masses. Hence, the diagnostic yield for detecting clinically significant pancreatic neoplasms was 5.3% (2 of 38). The 1 patient with pancreatic cancer was treated and still is alive and disease-free >5 years after surgery. EUS changes similar to those associated with chronic pancreatitis were found, which were more common in patients with a history of regular alcohol intake (P = 0.02), but also occurred in patients who did not consume alcohol. Screening also led to a new diagnosis and treatment of symptomatic upper-gastrointestinal conditions in 18.4% of patients.\nCONCLUSIONS: EUS-based screening of asymptomatic high-risk individuals can detect prevalent resectable pancreatic neoplasia but false-positive diagnoses also occur.","ISSN":"1542-3565","note":"PMID: 15224285","title-short":"Screening for pancreatic neoplasia in high-risk individuals","journalAbbreviation":"Clin. Gastroenterol. Hepatol.","language":"eng","author":[{"family":"Canto","given":"Marcia Irene"},{"family":"Goggins","given":"Michael"},{"family":"Yeo","given":"Charles J."},{"family":"Griffin","given":"Constance"},{"family":"Axilbund","given":"Jennifer E."},{"family":"Brune","given":"Kieran"},{"family":"Ali","given":"Syed Z."},{"family":"Jagannath","given":"Sanjay"},{"family":"Petersen","given":"Gloria M."},{"family":"Fishman","given":"Elliot K."},{"family":"Piantadosi","given":"Steven"},{"family":"Giardiello","given":"Francis M."},{"family":"Hruban","given":"Ralph H."}],"issued":{"date-parts":[["2004",7]]}}},{"id":"BbVydael/TT8LQAKI","uris":[""],"uri":[""],"itemData":{"id":79,"type":"article-journal","title":"Five years of prospective screening of high-risk individuals from families with familial pancreatic cancer","container-title":"Gut","page":"1410-1418","volume":"58","issue":"10","source":"PubMed","abstract":"OBJECTIVE: Familial pancreatic cancer (FPC) accounts for approximately 3% of all pancreatic cancer (PC) cases. It has been suggested that high-risk individuals (HRIs) should be offered a screening programme.\nAIM: To evaluate the diagnostic yield of a prospective screening programme in HRIs from families with FPC over a period of 5 years.\nMETHODS: HRIs of families with FPC of the National German Familial Pancreatic Cancer Registry (FaPaCa) were counselled and enrolled in a prospective, board-approved PC screening programme. Screening included clinical examination, laboratory tests, endoscopic ultrasound (EUS) and MRI with magnetic resonance cholangiopancreaticography (MRCP) and MR angiography.\nRESULTS: Between June 2002 and December 2007, 76 HRIs of families with FPC took part in the screening programme with a total of 182 examination visits. Twenty-eight patients revealed abnormalities in EUS (n = 25) and/or MR/MRCP (n = 12). In 7 patients fine needle aspiration cytology was performed. Operative pancreatic explorations were performed in 7 individuals, resulting in limited resections in 6 cases. Histopathological examination of the resected specimens showed serous oligocystic adenomas (n = 3), pancreatic intraepithelial neoplasia 1 (PanIN1) lesions with lobular fibrosis (n = 1), PanIN2 lesions (n = 1) and PanIN1 lesion plus a gastric type intraductal papillary mucinous neoplasm (IPMN) (n = 1).\nCONCLUSIONS: In FPC an EUS/MR/MRCP-based screening programme leads to the detection of potential precursor lesions of PC. However, the yield of an extensive screening programme is low, especially since the tumourigenic value of low grade PanIN lesions is not yet defined. Taking into account the enormous psychological stress for the tested individual and the high costs, a general PC screening in HRIs is not justified.","DOI":"10.1136/gut.2008.171611","ISSN":"1468-3288","note":"PMID: 19470496","journalAbbreviation":"Gut","language":"eng","author":[{"family":"Langer","given":"P."},{"family":"Kann","given":"P. H."},{"family":"Fendrich","given":"V."},{"family":"Habbe","given":"N."},{"family":"Schneider","given":"M."},{"family":"Sina","given":"M."},{"family":"Slater","given":"E. P."},{"family":"Heverhagen","given":"J. T."},{"family":"Gress","given":"T. M."},{"family":"Rothmund","given":"M."},{"family":"Bartsch","given":"D. K."}],"issued":{"date-parts":[["2009",10]]}}},{"id":"BbVydael/NFPiCpG1","uris":[""],"uri":[""],"itemData":{"id":46,"type":"article-journal","title":"Screening for early pancreatic neoplasia in high-risk individuals: a prospective controlled study","container-title":"Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association","page":"766-781; quiz 665","volume":"4","issue":"6","source":"PubMed","abstract":"BACKGROUND & AIMS: Individuals with a strong family history of pancreatic cancer and persons with Peutz-Jeghers syndrome (PJS) have an increased risk for pancreatic cancer. This study screened for early pancreatic neoplasia and compared the pancreatic abnormalities in high-risk individuals and control subjects.\nMETHODS: High-risk individuals with PJS or a strong family history of pancreatic cancer were prospectively evaluated with baseline and 12-month computed tomography (CT) scan and endoscopic ultrasonography (EUS). If EUS was abnormal, EUS-fine-needle aspiration and endoscopic retrograde cholangiopancreatography (ERCP) were performed. Surgery was offered to patients with potentially neoplastic lesions. Radiologic findings and pathologic diagnoses were compared. Patients undergoing EUS and/or ERCP for benign non-pancreatic indications were concurrently enrolled as control subjects.\nRESULTS: Seventy-eight high-risk patients (72 from familial pancreatic cancer kindreds, 6 PJS) and 149 control patients were studied. To date, 8 patients with pancreatic neoplasia have been confirmed by surgery or fine-needle aspiration (10% yield of screening); 6 patients had 8 benign intraductal papillary mucinous neoplasms (IPMNs), 1 had an IPMN that progressed to invasive ductal adenocarcinoma, and 1 had pancreatic intraepithelial neoplasia. EUS and CT also diagnosed 3 patients with 5 extrapancreatic neoplasms. At EUS and ERCP abnormalities suggestive of chronic pancreatitis were more common in high-risk patients than in control subjects.\nCONCLUSIONS: Screening EUS and CT diagnosed significant asymptomatic pancreatic and extrapancreatic neoplasms in high-risk individuals. IPMN should be considered a part of the phenotype of familial pancreatic cancer. Abnormalities suggestive of chronic pancreatitis are identified more commonly at EUS and ERCP in high-risk individuals.","DOI":"10.1016/j.cgh.2006.02.005","ISSN":"1542-3565","note":"PMID: 16682259","title-short":"Screening for early pancreatic neoplasia in high-risk individuals","journalAbbreviation":"Clin. Gastroenterol. Hepatol.","language":"eng","author":[{"family":"Canto","given":"Marcia Irene"},{"family":"Goggins","given":"Michael"},{"family":"Hruban","given":"Ralph H."},{"family":"Petersen","given":"Gloria M."},{"family":"Giardiello","given":"Francis M."},{"family":"Yeo","given":"Charles"},{"family":"Fishman","given":"Elliott K."},{"family":"Brune","given":"Kieran"},{"family":"Axilbund","given":"Jennifer"},{"family":"Griffin","given":"Constance"},{"family":"Ali","given":"Syed"},{"family":"Richman","given":"Jeffrey"},{"family":"Jagannath","given":"Sanjay"},{"family":"Kantsevoy","given":"Sergey V."},{"family":"Kalloo","given":"Anthony N."}],"issued":{"date-parts":[["2006",6]]}}},{"id":"BbVydael/KLfm1MxF","uris":[""],"uri":[""],"itemData":{"id":38,"type":"article-journal","title":"A multicentre comparative prospective blinded analysis of EUS and MRI for screening of pancreatic cancer in high-risk individuals","container-title":"Gut","page":"1505-1513","volume":"65","issue":"9","source":"PubMed","abstract":"OBJECTIVE: Endoscopic ultrasonography (EUS) and MRI are promising tests to detect precursors and early-stage pancreatic ductal adenocarcinoma (PDAC) in high-risk individuals (HRIs). It is unclear which screening technique is to be preferred. We aimed to compare the efficacy of EUS and MRI in their ability to detect clinically relevant lesions in HRI.\nDESIGN: Multicentre prospective study. The results of 139 asymptomatic HRI (>10-fold increased risk) undergoing first-time screening by EUS and MRI are described. Clinically relevant lesions were defined as solid lesions, main duct intraductal papillary mucinous neoplasms and cysts ≥10?mm. Results were compared in a blinded, independent fashion.\nRESULTS: Two solid lesions (mean size 9?mm) and nine cysts ≥10?mm (mean size 17?mm) were detected in nine HRI (6%). Both solid lesions were detected by EUS only and proved to be a stage I PDAC and a multifocal pancreatic intraepithelial neoplasia 2. Of the nine cysts ≥10?mm, six were detected by both imaging techniques and three were detected by MRI only. The agreement between EUS and MRI for the detection of clinically relevant lesions was 55%. Of these clinically relevant lesions detected by both techniques, there was a good agreement for location and size.\nCONCLUSIONS: EUS and/or MRI detected clinically relevant pancreatic lesions in 6% of HRI. Both imaging techniques were complementary rather than interchangeable: contrary to EUS, MRI was found to be very sensitive for the detection of cystic lesions of any size; MRI, however, might have some important limitations with regard to the timely detection of solid lesions.","DOI":"10.1136/gutjnl-2014-308008","ISSN":"1468-3288","note":"PMID: 25986944","journalAbbreviation":"Gut","language":"eng","author":[{"family":"Harinck","given":"F."},{"family":"Konings","given":"I. C. a. W."},{"family":"Kluijt","given":"I."},{"family":"Poley","given":"J. W."},{"family":"Hooft","given":"J. E.","non-dropping-particle":"van"},{"family":"Dullemen","given":"H. M.","non-dropping-particle":"van"},{"family":"Nio","given":"C. Y."},{"family":"Krak","given":"N. C."},{"family":"Hermans","given":"J. J."},{"family":"Aalfs","given":"C. M."},{"family":"Wagner","given":"A."},{"family":"Sijmons","given":"R. H."},{"family":"Biermann","given":"K."},{"family":"Eijck","given":"C. H.","non-dropping-particle":"van"},{"family":"Gouma","given":"D. J."},{"family":"Dijkgraaf","given":"M. G. W."},{"family":"Fockens","given":"P."},{"family":"Bruno","given":"M. J."},{"literal":"Dutch research group on pancreatic cancer surveillance in high-risk individuals"}],"issued":{"date-parts":[["2016"]]}}},{"id":"BbVydael/Sm6GTEmo","uris":[""],"uri":[""],"itemData":{"id":70,"type":"article-journal","title":"Benefit of Surveillance for Pancreatic Cancer in High-Risk Individuals: Outcome of Long-Term Prospective Follow-Up Studies From Three European Expert Centers","container-title":"Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology","page":"2010-2019","volume":"34","issue":"17","source":"PubMed","abstract":"PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis. Hereditary factors play a role in the development of PDAC in 3% to 5% of all patients. Surveillance of high-risk groups, may facilitate detection of PDAC at an early stage. The aim of this study was to assess whether surveillance aids detection of early-stage PDAC or precursor lesions (PRLs) and improves the prognosis.\nPATIENTS AND METHODS: Screening outcomes were collected from three European centers that conduct prospective screening in high-risk groups including families with clustering of PDAC (familial pancreatic cancer [FPC]) or families with a gene defect that predisposes to PDAC. The surveillance program consisted of annual magnetic resonance imaging, magnetic resonance cholangiopancreatography, and/or endoscopic ultrasound.\nRESULTS: Four hundred eleven asymptomatic individuals participated in the surveillance programs, including 178 CDKN2A mutation carriers, 214 individuals with FPC, and 19 BRCA1/2 or PALB2 mutation carriers. PDAC was detected in 13 (7.3%) of 178 CDKN2A mutation carriers. The resection rate was 75%, and the 5-year survival rate was 24%. Two CDKN2A mutation carriers (1%) underwent surgical resection for low-risk PRL. Two individuals (0.9%) in the FPC cohort had a pancreatic tumor, including one advanced PDAC and one early grade 2 neuroendocrine tumor. Thirteen individuals with FPC (6.1%) underwent surgical resection for a suspected PRL, but only four (1.9%) had high-risk lesions (ie, high-grade intraductal papillary mucinous neoplasms or grade 3 pancreatic intraepithelial neoplasms). One BRCA2 mutation carrier was found to have PDAC, and another BRCA2 mutation carrier and a PALB2 mutation carrier underwent surgery and were found to have low-risk PRL. No serious complications occurred as consequence of the program.\nCONCLUSION: Surveillance of CDNK2A mutation carriers is relatively successful, detecting most PDACs at a resectable stage. The benefit of surveillance in families with FPC is less evident.","DOI":"10.1200/JCO.2015.64.0730","ISSN":"1527-7755","note":"PMID: 27114589","title-short":"Benefit of Surveillance for Pancreatic Cancer in High-Risk Individuals","journalAbbreviation":"J. Clin. Oncol.","language":"eng","author":[{"family":"Vasen","given":"Hans"},{"family":"Ibrahim","given":"Isaura"},{"family":"Ponce","given":"Carmen Guillen"},{"family":"Slater","given":"Emily P."},{"family":"Matth?i","given":"Elvira"},{"family":"Carrato","given":"Alfredo"},{"family":"Earl","given":"Julie"},{"family":"Robbers","given":"Kristin"},{"family":"Mil","given":"Anneke M.","non-dropping-particle":"van"},{"family":"Potjer","given":"Thomas"},{"family":"Bonsing","given":"Bert A."},{"family":"Vos Tot Nederveen Cappel","given":"Wouter H.","non-dropping-particle":"de"},{"family":"Bergman","given":"Wilma"},{"family":"Wasser","given":"Martin"},{"family":"Morreau","given":"Hans"},{"family":"Kl?ppel","given":"Günter"},{"family":"Schicker","given":"Christoph"},{"family":"Steinkamp","given":"Martin"},{"family":"Figiel","given":"Jens"},{"family":"Esposito","given":"Irene"},{"family":"Mocci","given":"Evelina"},{"family":"Vazquez-Sequeiros","given":"Enrique"},{"family":"Sanjuanbenito","given":"Alfonso"},{"family":"Mu?oz-Beltran","given":"Maria"},{"family":"Montans","given":"José"},{"family":"Langer","given":"Peter"},{"family":"Fendrich","given":"Volker"},{"family":"Bartsch","given":"Detlef K."}],"issued":{"date-parts":[["2016"]],"season":"10"}}}],"schema":""} [12,15,23,27,31]. However, as previously reported, 7/26 HRI operated on for a “pancreatic mass” (27%) had lesions with no/low malignant potential on the pathological specimen ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"gaBMbV4V","properties":{"formattedCitation":"\\super [11]\\nosupersub{}","plainCitation":"[11]","noteIndex":0},"citationItems":[{"id":"BbVydael/iMJ7y1A2","uris":[""],"uri":[""],"itemData":{"id":33,"type":"article-journal","title":"Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma: a patient-level meta-analysis and proposition of the Beaujon score","container-title":"United European Gastroenterology Journal","page":"205064061882491","source":"Crossref","DOI":"10.1177/2050640618824910","ISSN":"2050-6406, 2050-6414","title-short":"Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma","language":"en","author":[{"family":"Mestier","given":"Louis","non-dropping-particle":"de"},{"family":"Muller","given":"Marie"},{"family":"Cros","given":"Jér?me"},{"family":"Vullierme","given":"Marie-Pierre"},{"family":"Vernerey","given":"Dewi"},{"family":"Maire","given":"Frédérique"},{"family":"Dokmak","given":"Safi"},{"family":"Rebours","given":"Vinciane"},{"family":"Sauvanet","given":"Alain"},{"family":"Lévy","given":"Philippe"},{"family":"Hammel","given":"Pascal"}],"issued":{"date-parts":[["2019",1,12]]}}}],"schema":""} [11]. Nevertheless, it is difficult to consider not operating on an HRI with a “pancreatic mass” identified during EUS screening ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1dcSiNSj","properties":{"formattedCitation":"\\super [11]\\nosupersub{}","plainCitation":"[11]","noteIndex":0},"citationItems":[{"id":"BbVydael/iMJ7y1A2","uris":[""],"uri":[""],"itemData":{"id":33,"type":"article-journal","title":"Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma: a patient-level meta-analysis and proposition of the Beaujon score","container-title":"United European Gastroenterology Journal","page":"205064061882491","source":"Crossref","DOI":"10.1177/2050640618824910","ISSN":"2050-6406, 2050-6414","title-short":"Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma","language":"en","author":[{"family":"Mestier","given":"Louis","non-dropping-particle":"de"},{"family":"Muller","given":"Marie"},{"family":"Cros","given":"Jér?me"},{"family":"Vullierme","given":"Marie-Pierre"},{"family":"Vernerey","given":"Dewi"},{"family":"Maire","given":"Frédérique"},{"family":"Dokmak","given":"Safi"},{"family":"Rebours","given":"Vinciane"},{"family":"Sauvanet","given":"Alain"},{"family":"Lévy","given":"Philippe"},{"family":"Hammel","given":"Pascal"}],"issued":{"date-parts":[["2019",1,12]]}}}],"schema":""} [11]. As discussed below, lesion sampling may be of special interest in this setting.Endoscopic ultrasound pancreatic screening techniques in high-risk individualsA study by Shin et al ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"G8BB7yNF","properties":{"formattedCitation":"\\super [29]\\nosupersub{}","plainCitation":"[29]","noteIndex":0},"citationItems":[{"id":"BbVydael/8dACpTCE","uris":[""],"uri":[""],"itemData":{"id":116,"type":"article-journal","title":"Linear-array EUS improves detection of pancreatic lesions in high-risk individuals: a randomized tandem study","container-title":"Gastrointestinal Endoscopy","page":"812-818","volume":"82","issue":"5","source":"PubMed","abstract":"BACKGROUND: Studies comparing linear and radial EUS for the detection of pancreatic lesions in an asymptomatic population with increased risk for pancreatic cancer are lacking.\nOBJECTIVES: To compare pancreatic lesion detection rates between radial and linear EUS and to determine the incremental diagnostic yield of a second EUS examination.\nDESIGN: Randomized controlled tandem study.\nSETTING: Five academic centers in the United States.\nPATIENTS: Asymptomatic high-risk individuals (HRIs) for pancreatic cancer undergoing screening EUS.\nINTERVENTIONS: Linear and radial EUS performed in randomized order.\nMAIN OUTCOME MEASUREMENTS: Pancreatic lesion detection rate by type of EUS, miss rate of 1 EUS examination, and incremental diagnostic yield of a second EUS examination (second-pass effect).\nRESULTS: Two hundred seventy-eight HRIs were enrolled, mean age 56 years (43.2%), and 90% were familial pancreatic cancer relatives. Two hundred twenty-four HRIs underwent tandem radial and linear EUS. When we used per-patient analysis, the overall prevalence of any pancreatic lesion was 45%. Overall, 16 of 224 HRIs (7.1%) had lesions missed during the initial EUS that were detected by the second EUS examination. The per-patient lesion miss rate was significantly greater for radial followed by linear EUS (9.8%) than for linear followed by radial EUS (4.5%) (P?= .03). When we used per-lesion analysis, 73 of 109 lesions (67%) were detected by radial EUS and 99 of 120 lesions (82%) were detected by linear EUS (P?< .001) during the first examination. The overall miss rate for a pancreatic lesion after 1 EUS examination was 47 of 229 (25%). The miss rate was significantly lower for linear EUS compared with radial EUS (17.5% vs 33.0%, P?= .007).\nLIMITATIONS: Most detected pancreatic lesions were not confirmed by pathology.\nCONCLUSION: Linear EUS detects more pancreatic lesions than radial EUS. There was a \"second-pass effect\" with additional lesions detected with a second EUS examination. This effect was significantly greater when linear EUS was used after an initial radial EUS examination.","DOI":"10.1016/j.gie.2015.02.028","ISSN":"1097-6779","note":"PMID: 25930097\nPMCID: PMC4609234","title-short":"Linear-array EUS improves detection of pancreatic lesions in high-risk individuals","journalAbbreviation":"Gastrointest. Endosc.","language":"eng","author":[{"family":"Shin","given":"Eun Ji"},{"family":"Topazian","given":"Mark"},{"family":"Goggins","given":"Michael G."},{"family":"Syngal","given":"Sapna"},{"family":"Saltzman","given":"John R."},{"family":"Lee","given":"Jeffrey H."},{"family":"Farrell","given":"James J."},{"family":"Canto","given":"Marcia I."}],"issued":{"date-parts":[["2015",11]]}}}],"schema":""} [29] suggested that compared to radial EUS, linear-array?EUS?improves the detection of?pancreatic?lesions in?HRI, probably due to better visualization of the pancreatic tail. This same study reported a "second-pass effect" with additional lesions detected during a second?EUS?examination ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"bOJERs7R","properties":{"formattedCitation":"\\super [29]\\nosupersub{}","plainCitation":"[29]","noteIndex":0},"citationItems":[{"id":"BbVydael/8dACpTCE","uris":[""],"uri":[""],"itemData":{"id":116,"type":"article-journal","title":"Linear-array EUS improves detection of pancreatic lesions in high-risk individuals: a randomized tandem study","container-title":"Gastrointestinal Endoscopy","page":"812-818","volume":"82","issue":"5","source":"PubMed","abstract":"BACKGROUND: Studies comparing linear and radial EUS for the detection of pancreatic lesions in an asymptomatic population with increased risk for pancreatic cancer are lacking.\nOBJECTIVES: To compare pancreatic lesion detection rates between radial and linear EUS and to determine the incremental diagnostic yield of a second EUS examination.\nDESIGN: Randomized controlled tandem study.\nSETTING: Five academic centers in the United States.\nPATIENTS: Asymptomatic high-risk individuals (HRIs) for pancreatic cancer undergoing screening EUS.\nINTERVENTIONS: Linear and radial EUS performed in randomized order.\nMAIN OUTCOME MEASUREMENTS: Pancreatic lesion detection rate by type of EUS, miss rate of 1 EUS examination, and incremental diagnostic yield of a second EUS examination (second-pass effect).\nRESULTS: Two hundred seventy-eight HRIs were enrolled, mean age 56 years (43.2%), and 90% were familial pancreatic cancer relatives. Two hundred twenty-four HRIs underwent tandem radial and linear EUS. When we used per-patient analysis, the overall prevalence of any pancreatic lesion was 45%. Overall, 16 of 224 HRIs (7.1%) had lesions missed during the initial EUS that were detected by the second EUS examination. The per-patient lesion miss rate was significantly greater for radial followed by linear EUS (9.8%) than for linear followed by radial EUS (4.5%) (P?= .03). When we used per-lesion analysis, 73 of 109 lesions (67%) were detected by radial EUS and 99 of 120 lesions (82%) were detected by linear EUS (P?< .001) during the first examination. The overall miss rate for a pancreatic lesion after 1 EUS examination was 47 of 229 (25%). The miss rate was significantly lower for linear EUS compared with radial EUS (17.5% vs 33.0%, P?= .007).\nLIMITATIONS: Most detected pancreatic lesions were not confirmed by pathology.\nCONCLUSION: Linear EUS detects more pancreatic lesions than radial EUS. There was a \"second-pass effect\" with additional lesions detected with a second EUS examination. This effect was significantly greater when linear EUS was used after an initial radial EUS examination.","DOI":"10.1016/j.gie.2015.02.028","ISSN":"1097-6779","note":"PMID: 25930097\nPMCID: PMC4609234","title-short":"Linear-array EUS improves detection of pancreatic lesions in high-risk individuals","journalAbbreviation":"Gastrointest. Endosc.","language":"eng","author":[{"family":"Shin","given":"Eun Ji"},{"family":"Topazian","given":"Mark"},{"family":"Goggins","given":"Michael G."},{"family":"Syngal","given":"Sapna"},{"family":"Saltzman","given":"John R."},{"family":"Lee","given":"Jeffrey H."},{"family":"Farrell","given":"James J."},{"family":"Canto","given":"Marcia I."}],"issued":{"date-parts":[["2015",11]]}}}],"schema":""} [29].The use of contrast-enhanced harmonic EUS (CH-EUS) could improve its diagnostic performance. Indeed, it can identify solid neoplastic components in pancreatic cysts/IPMN as hyperenhanced lesions (Figure 5) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"xPRAbqic","properties":{"formattedCitation":"\\super [56]\\nosupersub{}","plainCitation":"[56]","noteIndex":0},"citationItems":[{"id":"BbVydael/yOFWRIUm","uris":[""],"uri":[""],"itemData":{"id":199,"type":"article-journal","title":"The clinical impact of ultrasound contrast agents in EUS: a?systematic review according to the levels of evidence","container-title":"Gastrointestinal Endoscopy","page":"587-596.e10","volume":"84","issue":"4","source":"PubMed","abstract":"BACKGROUND AND AIMS: The use of contrast-harmonic EUS (CH-EUS) in routine clinical practice is increasing rapidly but is not yet standardized. We present the levels of evidence (LEs) found in the literature to put its clinical outcomes in the appropriate perspective.\nMETHODS: We conducted a systematic review of the available English-language articles. The LEs were stratified according to the Oxford Centre for Evidence-Based Medicine guidelines.\nRESULTS: Overall, 210 articles were included and presented according to different pathologic conditions. For pancreatic solid neoplasms, the pooled sensitivity and specificity in the diagnosis of pancreatic carcinoma were very high (LE 1); quantitative analysis and guidance of FNA were reported as investigational research (LE 2-3). For pancreatic cystic lesions, the identification of neoplastic solid components as hyperenhanced lesions represented a promising application of CH-EUS (LE 2). For lymph nodes, CH-EUS increased the diagnostic yield of B-mode EUS for the detection of malignancy (LE 2). For submucosal tumors, CH-EUS seemed useful for differential diagnosis and risk stratification (LE 2-3). For other applications, differential diagnosis of gallbladder and vascular abnormalities by CH-EUS were reported (LE 2-3).\nCONCLUSIONS: The LEs of CH-EUS in the literature have evolved from the initial descriptive studies to multicenter and prospective trials, and even meta-analyses. The differential diagnosis between benign and malignant lesions is the main field of application of CH-EUS. With regard to pancreatic solid neoplasms, the concomitant use of both CH-EUS and EUS-FNA may have additive value in increasing the overall accuracy by overcoming the false-negative results associated with each individual technique. Other applications are promising but still investigational.","DOI":"10.1016/j.gie.2016.06.006","ISSN":"1097-6779","note":"PMID: 27311654","title-short":"The clinical impact of ultrasound contrast agents in EUS","journalAbbreviation":"Gastrointest. Endosc.","language":"eng","author":[{"family":"Fusaroli","given":"Pietro"},{"family":"Napoleon","given":"Bertrand"},{"family":"Gincul","given":"Rodica"},{"family":"Lefort","given":"Christine"},{"family":"Palazzo","given":"Laurent"},{"family":"Palazzo","given":"Maxime"},{"family":"Kitano","given":"Masayuki"},{"family":"Minaga","given":"Kosuke"},{"family":"Caletti","given":"Giancarlo"},{"family":"Lisotti","given":"Andrea"}],"issued":{"date-parts":[["2016",10]]}}}],"schema":""} [56]. The pooled sensitivity and specificity of CH-EUS for the diagnosis of PC are very high (91% and 87%, respectively) in the general population with solid pancreatic neoplasms ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"u0bktSeR","properties":{"formattedCitation":"\\super [56,57]\\nosupersub{}","plainCitation":"[56,57]","noteIndex":0},"citationItems":[{"id":"BbVydael/RbuHzUFs","uris":[""],"uri":[""],"itemData":{"id":164,"type":"article-journal","title":"Diagnostic performance of contrast-enhanced ultrasound for pancreatic neoplasms: A systematic review and meta-analysis","container-title":"Digestive and Liver Disease: Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver","page":"132-138","volume":"50","issue":"2","source":"PubMed","abstract":"BACKGROUND: Early diagnosis of pancreatic cancer is essential to optimize treatment strategies.\nOBJECTIVES: To evaluate the diagnostic performance of contrast-enhanced ultrasound for benign and malignant pancreatic neoplasms.\nDATA SOURCES: Pubmed, Embase, Web of Science, and Cochrane Library databases.\nSTUDY ELIGIBILITY CRITERIA: Retrospective or prospective studies.\nPARTICIPANTS: Patients with a confirmed diagnosis of benign and malignant pancreatic neoplasms.\nINTERVENTION: Contrast-enhanced ultrasound.\nSTUDY APPRAISAL AND SYNTHESIS: Pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic risk ratio, and corresponding 95% confidence intervals; summary receiver operating characteristic (SROC) curve; a Fagan nomogram.\nRESULTS: Ten studies involving 641 patients were included. Pooled sensitivity, specificity, and positive and negative predictive values were 91% (95% CI: 87%, 93%), 87% (95% CI: 78%, 93%), 7.2 (95% CI: 4.3, 12.3), and 0.11 (95% CI: 0.08, 0.15), respectively; and the odds ratio for diagnosis was 67 (95% CI: 34, 113). Contrast-enhanced ultrasound had good diagnostic ability and accuracy. Pre- and post-test probability of disease was 50% and 88%, respectively, when the positive likelihood ratio was 7.\nCONCLUSION: Contrast-enhanced ultrasound can be used for qualitative diagnosis of benign and malignant pancreatic neoplasms.\nIMPLICATIONS OF KEY FINDINGS: CEUS should be considered as an important imaging tool for the characterization of pancreatic tumors.\nSYSTEMATIC REVIEW REGISTRATION NUMBER: CRD42017070434 (PROSPERO).","DOI":"10.1016/j.dld.2017.10.012","ISSN":"1878-3562","note":"PMID: 29162410","title-short":"Diagnostic performance of contrast-enhanced ultrasound for pancreatic neoplasms","journalAbbreviation":"Dig Liver Dis","language":"eng","author":[{"family":"Li","given":"Xing-Zhao"},{"family":"Song","given":"Jun"},{"family":"Sun","given":"Zhi-Xia"},{"family":"Yang","given":"Yan-Yan"},{"family":"Wang","given":"Hui"}],"issued":{"date-parts":[["2018",2]]}}},{"id":"BbVydael/yOFWRIUm","uris":[""],"uri":[""],"itemData":{"id":199,"type":"article-journal","title":"The clinical impact of ultrasound contrast agents in EUS: a?systematic review according to the levels of evidence","container-title":"Gastrointestinal Endoscopy","page":"587-596.e10","volume":"84","issue":"4","source":"PubMed","abstract":"BACKGROUND AND AIMS: The use of contrast-harmonic EUS (CH-EUS) in routine clinical practice is increasing rapidly but is not yet standardized. We present the levels of evidence (LEs) found in the literature to put its clinical outcomes in the appropriate perspective.\nMETHODS: We conducted a systematic review of the available English-language articles. The LEs were stratified according to the Oxford Centre for Evidence-Based Medicine guidelines.\nRESULTS: Overall, 210 articles were included and presented according to different pathologic conditions. For pancreatic solid neoplasms, the pooled sensitivity and specificity in the diagnosis of pancreatic carcinoma were very high (LE 1); quantitative analysis and guidance of FNA were reported as investigational research (LE 2-3). For pancreatic cystic lesions, the identification of neoplastic solid components as hyperenhanced lesions represented a promising application of CH-EUS (LE 2). For lymph nodes, CH-EUS increased the diagnostic yield of B-mode EUS for the detection of malignancy (LE 2). For submucosal tumors, CH-EUS seemed useful for differential diagnosis and risk stratification (LE 2-3). For other applications, differential diagnosis of gallbladder and vascular abnormalities by CH-EUS were reported (LE 2-3).\nCONCLUSIONS: The LEs of CH-EUS in the literature have evolved from the initial descriptive studies to multicenter and prospective trials, and even meta-analyses. The differential diagnosis between benign and malignant lesions is the main field of application of CH-EUS. With regard to pancreatic solid neoplasms, the concomitant use of both CH-EUS and EUS-FNA may have additive value in increasing the overall accuracy by overcoming the false-negative results associated with each individual technique. Other applications are promising but still investigational.","DOI":"10.1016/j.gie.2016.06.006","ISSN":"1097-6779","note":"PMID: 27311654","title-short":"The clinical impact of ultrasound contrast agents in EUS","journalAbbreviation":"Gastrointest. Endosc.","language":"eng","author":[{"family":"Fusaroli","given":"Pietro"},{"family":"Napoleon","given":"Bertrand"},{"family":"Gincul","given":"Rodica"},{"family":"Lefort","given":"Christine"},{"family":"Palazzo","given":"Laurent"},{"family":"Palazzo","given":"Maxime"},{"family":"Kitano","given":"Masayuki"},{"family":"Minaga","given":"Kosuke"},{"family":"Caletti","given":"Giancarlo"},{"family":"Lisotti","given":"Andrea"}],"issued":{"date-parts":[["2016",10]]}}}],"schema":""} [56,57]. Nevertheless, there is no specific study on the use of CH-EUS for pancreatic screening in HRI. EUS elastography could also be useful for the characterization of solid pancreatic lesions in this population ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"vuCZO4Im","properties":{"formattedCitation":"\\super [58]\\nosupersub{}","plainCitation":"[58]","noteIndex":0},"citationItems":[{"id":"BbVydael/szXF2ZeB","uris":[""],"uri":[""],"itemData":{"id":166,"type":"article-journal","title":"Elastography for the pancreas: Current status and future perspective","container-title":"World Journal of Gastroenterology","page":"3712-3724","volume":"22","issue":"14","source":"PubMed","abstract":"Elastography for the pancreas can be performed by either ultrasound or endoscopic ultrasound (EUS). There are two types of pancreatic elastographies based on different principles, which are strain elastography and shear wave elastography. The stiffness of tissue is estimated by measuring the grade of strain generated by external pressure in the former, whereas it is estimated by measuring propagation speed of shear wave, the transverse wave, generated by acoustic radiation impulse (ARFI) in the latter. Strain elastography is difficult to perform when the probe, the pancreas and the aorta are not located in line. Accordingly, a fine elastogram can be easily obtained in the pancreatic body but not in the pancreatic head and tail. In contrast, shear wave elastography can be easily performed in the entire pancreas because ARFI can be emitted to wherever desired. However, shear wave elastography cannot be performed by EUS to date. Recently, clinical guidelines for elastography specialized in the pancreas were published from Japanese Society of Medical Ultrasonics. The guidelines show us technical knacks of performing elastography for the pancreas.","DOI":"10.3748/wjg.v22.i14.3712","ISSN":"2219-2840","note":"PMID: 27076756\nPMCID: PMC4814734","title-short":"Elastography for the pancreas","journalAbbreviation":"World J. Gastroenterol.","language":"eng","author":[{"family":"Kawada","given":"Natsuko"},{"family":"Tanaka","given":"Sachiko"}],"issued":{"date-parts":[["2016",4,14]]}}}],"schema":""} [58]. Iglesias-Garcia et al ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"hj2gRKOc","properties":{"formattedCitation":"\\super [59]\\nosupersub{}","plainCitation":"[59]","noteIndex":0},"citationItems":[{"id":"BbVydael/r6jQCGOx","uris":[""],"uri":[""],"itemData":{"id":169,"type":"article-journal","title":"EUS elastography for the characterization of solid pancreatic masses","container-title":"Gastrointestinal Endoscopy","page":"1101-1108","volume":"70","issue":"6","source":"PubMed","abstract":"BACKGROUND: Differential diagnosis of solid pancreatic masses remains a challenge. EUS elastography, by analyzing tissue stiffness of the mass, may be of help in this setting.\nOBJECTIVE: To evaluate the different elastographic patterns of solid pancreatic masses and the diagnostic accuracy of EUS elastography for malignancy.\nDESIGN: Prospective, consecutive, descriptive study with a second blind evaluation of elastographic patterns for concordance analysis and use of a well-defined reference method for calculation of diagnostic accuracy.\nPATIENTS: This study involved 130 consecutive patients with solid pancreatic masses and 20 controls with normal pancreases.\nINTERVENTION: EUS elastography was performed by using a linear Pentax echoendoscope and Hitachi EUB-8500 US.\nMAIN OUTCOME MEASUREMENTS: Elastographic patterns of solid pancreatic masses and accuracy of the technique for malignancy.\nRESULTS: Mean (SD) size of the masses was 30.9 (12.5) mm. The final diagnosis was malignant tumor in 78 patients, inflammatory mass in 42 patients, and neuroendocrine tumor in 10 patients. Four elastographic patterns were described, with a high concordance among 2 blinded investigators. A green-predominant pattern, either homogeneous or heterogeneous, excluded malignancy with a high accuracy. On the contrary, a blue-predominant pattern, either homogeneous or heterogeneous, supported the diagnosis of malignant tumor. Sensitivity, specificity, positive and negative predictive values, and overall accuracy of EUS elastography for diagnosis of malignancy were 100%, 85.5%, 90.7%, 100%, and 94.0%, respectively.\nLIMITATION: Single-center study.\nCONCLUSION: EUS elastography is a useful tool for differential diagnosis of solid pancreatic masses. It provides specific patterns supporting the benign or malignant nature of the disease.","DOI":"10.1016/j.gie.2009.05.011","ISSN":"1097-6779","note":"PMID: 19647248","journalAbbreviation":"Gastrointest. Endosc.","language":"eng","author":[{"family":"Iglesias-Garcia","given":"Julio"},{"family":"Larino-Noia","given":"Jose"},{"family":"Abdulkader","given":"Ihab"},{"family":"Forteza","given":"Jeronimo"},{"family":"Dominguez-Munoz","given":"J. Enrique"}],"issued":{"date-parts":[["2009",12]]}}}],"schema":""} [59] reported a sensitivity, a specificity, and positive and negative predictive values of 100%, 85.5%, 90.7%, and 100%, respectively, for the diagnosis of sporadic PC.The results of certain new techniques for the detection of (pre)malignant pancreatic lesions are especially promising in HRI, including the molecular imaging of cathepsin E in vivo using a confocal laser endomicroscopy miniprobe (overexpression of cathepsin E in PanIN) and the detection of DNA abnormalities or protein markers in pancreatic cyst fluid collected by fine needle aspiration (FNA) (mutations in genes such as TP53) (Figure 6) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"8EnU4Gx2","properties":{"formattedCitation":"\\super [57,60\\uc0\\u8211{}63]\\nosupersub{}","plainCitation":"[57,60–63]","noteIndex":0},"citationItems":[{"id":"BbVydael/RbuHzUFs","uris":[""],"uri":[""],"itemData":{"id":164,"type":"article-journal","title":"Diagnostic performance of contrast-enhanced ultrasound for pancreatic neoplasms: A systematic review and meta-analysis","container-title":"Digestive and Liver Disease: Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver","page":"132-138","volume":"50","issue":"2","source":"PubMed","abstract":"BACKGROUND: Early diagnosis of pancreatic cancer is essential to optimize treatment strategies.\nOBJECTIVES: To evaluate the diagnostic performance of contrast-enhanced ultrasound for benign and malignant pancreatic neoplasms.\nDATA SOURCES: Pubmed, Embase, Web of Science, and Cochrane Library databases.\nSTUDY ELIGIBILITY CRITERIA: Retrospective or prospective studies.\nPARTICIPANTS: Patients with a confirmed diagnosis of benign and malignant pancreatic neoplasms.\nINTERVENTION: Contrast-enhanced ultrasound.\nSTUDY APPRAISAL AND SYNTHESIS: Pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic risk ratio, and corresponding 95% confidence intervals; summary receiver operating characteristic (SROC) curve; a Fagan nomogram.\nRESULTS: Ten studies involving 641 patients were included. Pooled sensitivity, specificity, and positive and negative predictive values were 91% (95% CI: 87%, 93%), 87% (95% CI: 78%, 93%), 7.2 (95% CI: 4.3, 12.3), and 0.11 (95% CI: 0.08, 0.15), respectively; and the odds ratio for diagnosis was 67 (95% CI: 34, 113). Contrast-enhanced ultrasound had good diagnostic ability and accuracy. Pre- and post-test probability of disease was 50% and 88%, respectively, when the positive likelihood ratio was 7.\nCONCLUSION: Contrast-enhanced ultrasound can be used for qualitative diagnosis of benign and malignant pancreatic neoplasms.\nIMPLICATIONS OF KEY FINDINGS: CEUS should be considered as an important imaging tool for the characterization of pancreatic tumors.\nSYSTEMATIC REVIEW REGISTRATION NUMBER: CRD42017070434 (PROSPERO).","DOI":"10.1016/j.dld.2017.10.012","ISSN":"1878-3562","note":"PMID: 29162410","title-short":"Diagnostic performance of contrast-enhanced ultrasound for pancreatic neoplasms","journalAbbreviation":"Dig Liver Dis","language":"eng","author":[{"family":"Li","given":"Xing-Zhao"},{"family":"Song","given":"Jun"},{"family":"Sun","given":"Zhi-Xia"},{"family":"Yang","given":"Yan-Yan"},{"family":"Wang","given":"Hui"}],"issued":{"date-parts":[["2018",2]]}}},{"id":"BbVydael/MBLxDZhw","uris":[""],"uri":[""],"itemData":{"id":126,"type":"article-journal","title":"Endoscopic ultrasonography for surveillance of individuals at high risk for pancreatic cancer","container-title":"World Journal of Gastrointestinal Endoscopy","page":"272-285","volume":"6","issue":"7","source":"PubMed","abstract":"Pancreatic cancer is a highly lethal disease with a genetic susceptibility and familial aggregation found in 3%-16% of patients. Early diagnosis remains the only hope for curative treatment and improvement of prognosis. This can be reached by the implementation of an intensive screening program, actually recommended for individuals at high-risk for pancreatic cancer development. The aim of this strategy is to identify pre-malignant precursors or asymptomatic pancreatic cancer lesions, curable by surgery. Endoscopic ultrasound (EUS) with or without fine needle aspiration (FNA) seems to be the most promising technique for early detection of pancreatic cancer. It has been described as a highly sensitive and accurate tool, especially for small and cystic lesions. Pancreatic intraepithelial neoplasia, a precursor lesion which is highly represented in high-risk individuals, seems to have characteristics chronic pancreatitis-like changes well detected by EUS. Many screening protocols have demonstrated high diagnostic yields for pancreatic pre-malignant lesions, allowing prophylactic pancreatectomies. However, it shows a high interobserver variety even among experienced endosonographers and a low sensitivity in case of chronic pancreatitis. Some new techniques such as contrast-enhanced harmonic EUS, computer-aided diagnostic techniques, confocal laser endomicroscopy miniprobe and the detection of DNA abnormalities or protein markers by FNA, promise improvement of the diagnostic yield of EUS. As the resolution of imaging improves and as our knowledge of precursor lesions grows, we believe that EUS could become the most suitable method to detect curable pancreatic neoplasms in correctly identified asymptomatic at-risk patients.","DOI":"10.4253/wjge.v6.i7.272","ISSN":"1948-5190","note":"PMID: 25031786\nPMCID: PMC4094985","journalAbbreviation":"World J Gastrointest Endosc","language":"eng","author":[{"family":"Lami","given":"Gabriele"},{"family":"Biagini","given":"Maria Rosa"},{"family":"Galli","given":"Andrea"}],"issued":{"date-parts":[["2014",7,16]]}}},{"id":"BbVydael/OmgS1ZHT","uris":[""],"uri":[""],"itemData":{"id":111,"type":"article-journal","title":"The role of endoscopic ultrasound in pancreatic cancer screening","container-title":"Endoscopic Ultrasound","page":"8-16","volume":"5","issue":"1","source":"PubMed","abstract":"Pancreatic cancer (PC) is a highly lethal cancer. Despite a significant advancement in cancer treatment, the mortality rate of PC is nearly identical to the incidence rates. Early detection of tumor or its precursor lesions with dysplasia may be the most effective approach to improve survival. Screening strategies should include identification of the population at high risk of developing PC, and an intense application of screening tools with adequate sensitivity to detect PC at an early curable stage. Endoscopic ultrasound (EUS) and magnetic resonance imaging (MRI) seem to be the most promising modalities for PC screening based on the data so far. EUS had an additional advantage over MRI by being able to obtain tissue sample during the same examination. Several questions remain unanswered at this time regarding the age to begin screening, frequency of screening, management of asymptomatic pancreatic lesions detected on screening, timing of resection, and extent of surgery and impact of screening on survival. Novel techniques such as needle-based confocal laser endomicroscopy (nCLE), along with biomarkers, may be helpful to identify pancreatic lesions with more aggressive malignant potential. Further studies will hopefully lead to the development of strategies combining EUS with other technological/biological advancements that will be cost-effective and have an impact on survival.","DOI":"10.4103/2303-9027.175876","ISSN":"2303-9027","note":"PMID: 26879161\nPMCID: PMC4770628","journalAbbreviation":"Endosc Ultrasound","language":"eng","author":[{"family":"Bhutani","given":"Manoop S."},{"family":"Koduru","given":"Pramoda"},{"family":"Joshi","given":"Virendra"},{"family":"Saxena","given":"Payal"},{"family":"Suzuki","given":"Rei"},{"family":"Irisawa","given":"Atsushi"},{"family":"Yamao","given":"Kenji"}],"issued":{"date-parts":[["2016",2]]}}},{"id":"BbVydael/D9wM6xdO","uris":[""],"uri":[""],"itemData":{"id":174,"type":"article-journal","title":"Mutant TP53 in duodenal samples of pancreatic juice from patients with pancreatic cancer or high-grade dysplasia","container-title":"Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association","page":"719-730.e5","volume":"11","issue":"6","source":"PubMed","abstract":"BACKGROUND & AIMS: Imaging tests can identify patients with pancreatic neoplastic cysts but not microscopic dysplasia. We investigated whether mutant TP53 can be detected in duodenal samples of secretin-stimulated pancreatic juice, and whether this assay can be used to screen for high-grade dysplasia and invasive pancreatic cancer.\nMETHODS: We determined the prevalence of mutant TP53 in microdissected pancreatic intraepithelial neoplasias (PanINs), intraductal papillary mucinous neoplasms (IPMNs), and invasive adenocarcinomas. TP53 mutations were quantified by digital high-resolution melt-curve analysis and sequencing of secretin-stimulated pancreatic juice samples, collected from duodena of 180 subjects enrolled in Cancer of the Pancreas Screening trials; patients were enrolled because of familial and/or inherited predisposition to pancreatic cancer, or as controls.\nRESULTS: TP53 mutations were identified in 9.1% of intermediate-grade IPMNs (2 of 22), 17.8% of PanIN-2 (8 of 45), 38.1% of high-grade IPMNs (8 of 21), 47.6% of PanIN-3 (10 of 21), and 75% of invasive pancreatic adenocarcinomas (15 of 20); no TP53 mutations were found in PanIN-1 lesions or low-grade IPMNs. TP53 mutations were detected in duodenal samples of pancreatic juice from 29 of 43 patients with pancreatic ductal adenocarcinoma (67.4% sensitivity; 95% confidence interval, 0.52-0.80) and 4 of 8 patients with high-grade lesions (PanIN-3 and high-grade IPMN). No TP53 mutations were identified in samples from 58 controls or 55 screened individuals without evidence of advanced lesions.\nCONCLUSIONS: We detected mutant TP53 in secretin-stimulated pancreatic juice samples collected from duodena of patients with high-grade dysplasia or invasive pancreatic cancer. Tests for mutant TP53 might be developed to improve the diagnosis of and screening for pancreatic cancer and high-grade dysplasia. Clinical Trial numbers: NCT00438906 and NCT00714701.","DOI":"10.1016/j.cgh.2012.11.016","ISSN":"1542-7714","note":"PMID: 23200980\nPMCID: PMC3600161","journalAbbreviation":"Clin. Gastroenterol. Hepatol.","language":"eng","author":[{"family":"Kanda","given":"Mitsuro"},{"family":"Sadakari","given":"Yoshihiko"},{"family":"Borges","given":"Michael"},{"family":"Topazian","given":"Mark"},{"family":"Farrell","given":"James"},{"family":"Syngal","given":"Sapna"},{"family":"Lee","given":"Jeffrey"},{"family":"Kamel","given":"Ihab"},{"family":"Lennon","given":"Anne Marie"},{"family":"Knight","given":"Spencer"},{"family":"Fujiwara","given":"Sho"},{"family":"Hruban","given":"Ralph H."},{"family":"Canto","given":"Marcia Irene"},{"family":"Goggins","given":"Michael"}],"issued":{"date-parts":[["2013",6]]}}},{"id":"BbVydael/v6Slt5pD","uris":[""],"uri":[""],"itemData":{"id":177,"type":"article-journal","title":"Role of endoscopic ultrasound in the molecular diagnosis of pancreatic cancer","container-title":"World Journal of Gastroenterology","page":"10758-10768","volume":"20","issue":"31","source":"PubMed","abstract":"Pancreatic ductal adenocarcinoma remains one of the most deadly types of tumor. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a safe, cost-effective, and accurate technique for evaluating and staging pancreatic tumors. However, EUS-FNA may be inconclusive or doubtful in up to 20% of cases. This review underlines the clinical interest of the molecular analysis of samples obtained by EUS-FNA in assessing diagnosis or prognosis of pancreatic cancer, especially in locally advanced tumors. On EUS-FNA materials DNA, mRNA and miRNA can be extracted, amplified, quantified and subjected to methylation assay. Kras mutation assay, improves diagnosis of pancreatic cancer. When facing to clinical and radiological presentations of pseudo-tumorous chronic pancreatitis, wild-type Kras is evocative of benignity. Conversely, in front of a pancreatic mass suspected of malignancy, a mutated Kras is highly evocative of pancreatic adenocarcinoma. This strategy can reduce false-negative diagnoses, avoids the delay of making decisions and reduces loss of surgical resectability. Similar approaches are conducted using analysis of miRNA expression as well as Mucin or markers of invasion (S100P, S100A6, PLAT or PLAU). Beyond the diagnosis approach, the prediction of response to treatment can be also investigated form biomarkers expression within EUS-FNA materials.","DOI":"10.3748/wjg.v20.i31.10758","ISSN":"2219-2840","note":"PMID: 25152579\nPMCID: PMC4138456","journalAbbreviation":"World J. Gastroenterol.","language":"eng","author":[{"family":"Bournet","given":"Barbara"},{"family":"Gayral","given":"Marion"},{"family":"Torrisani","given":"Jér?me"},{"family":"Selves","given":"Janick"},{"family":"Cordelier","given":"Pierre"},{"family":"Buscail","given":"Louis"}],"issued":{"date-parts":[["2014",8,21]]}}}],"schema":""} [57,60–63]. The role of these combined strategies (EUS?with other new technological/biological techniques) as well as their impact on survival and cost-effectiveness must, however, still be defined ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"USNdXTcD","properties":{"formattedCitation":"\\super [64]\\nosupersub{}","plainCitation":"[64]","noteIndex":0},"citationItems":[{"id":"BbVydael/VHic5mPp","uris":[""],"uri":[""],"itemData":{"id":180,"type":"article-journal","title":"Pancreatic cyst fluid analysis--a review","container-title":"Journal of gastrointestinal and liver diseases: JGLD","page":"175-180","volume":"20","issue":"2","source":"PubMed","abstract":"An increased number of pancreatic cysts are being diagnosed due to the increased usage of cross-sectional imaging. Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) cytology and molecular analysis of these cystic lesions have led to their better detection and characterization. The aim of this review is to assess the value of cyst fluid analysis for the differential diagnosis of pancreatic cystic lesions, in view of the recent progresses of molecular analysis methods. Pancreatic cysts can be either simple (retention) cysts, pseudocysts and cystic neoplasms, while these are further subdivided into serous cystadenomas, mucinous cystic neoplasms (MCNs) or intraductal papillary mucinous neoplasms (IPMNs). EUS is now being used to investigate cystic pancreatic lesions, particularly by means of EUS guided cyst aspiration and sampling of the cyst wall or septa, as well as mural nodules. Cyst fluid can be further studied after aspiration in order to analyze cytology, viscosity, extracellular mucin, other tumor markers (CEA, CA 19-9,CA 15-3, Ca 72-4, etc.), enzymes (amylase, lipase), as well as DNA analysis of DNA quality/content or mutational analysis to study allelic imbalance/LOH (loss of heterozygosity) and K-ras mutations. After careful review of the published studies, a conclusion was reached that the use of tumor and molecular markers in conjunction with multimodality detection methods such as CT, MR and EUS-FNA allows risk stratification, while being also cost-effective.","ISSN":"1842-1121","note":"PMID: 21725515","journalAbbreviation":"J Gastrointestin Liver Dis","language":"eng","author":[{"family":"Bhutani","given":"Manoop S."},{"family":"Gupta","given":"Vikas"},{"family":"Guha","given":"Sushovan"},{"family":"Gheonea","given":"Dan Ionu?"},{"family":"Saftoiu","given":"Adrian"}],"issued":{"date-parts":[["2011",6]]}}}],"schema":""} [64]. Finally, another lead could also be the identification of molecular abnormalities (p53 mutations, KRAS mutations, DNA methylation markers) associated with the presence of PC and precursors of PC within pancreatic fluid collected by endoscopic retrograde cholangiopancreatography ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"ALGiEdkg","properties":{"formattedCitation":"\\super [65\\uc0\\u8211{}69]\\nosupersub{}","plainCitation":"[65–69]","noteIndex":0},"citationItems":[{"id":"BbVydael/IGb9bw90","uris":[""],"uri":[""],"itemData":{"id":215,"type":"article-journal","title":"Molecular diagnosis of early pancreatic ductal adenocarcinoma in high-risk patients","container-title":"Pancreatology: official journal of the International Association of Pancreatology (IAP) ... [et al.]","page":"486-509","volume":"1","issue":"5","source":"PubMed","abstract":"The prevalence of pancreatic cancer in the general population is too low--even in high-prevalence areas such as Northern Europe and North America (8-12 per 10(5) population)--relative to the diagnostic accuracy of present detection methods to permit primary screening in the asymptomatic adult population. The recognition that the lifetime risk of developing pancreatic cancer for patients with hereditary pancreatitis (HP) is extremely high (20% by the age of 60 years and 40% by the age of 70 years) poses considerable challenges and opportunities for secondary screening in those patients without any clinical features of pancreatic cancer. Even for secondary screening, the detection of cancer at a biological stage that would be amenable to cure by surgery (total pancreatectomy) still requires diagnostic modalities with a very high sensitivity and specificity. Conventional radiological imaging methods such as endoluminal ultrasound and endoscopic retrograde pancreatography, which have proved to be valuable in the early detection of early neoplastic lesions in patients with familial pancreatic cancer, may well be applicable to patients with HP but only in those without gross morphological features of chronic pancreatitis (other than parenchymal atrophy). Unfortunately, most cases of HP also have associated gross features of chronic pancreatitis that are likely to seriously undermine the diagnostic value of these conventional imaging modalities. Pre-malignant molecular changes can be detected in the pancreatic juice of patients. Thus, the application of molecular screening in patients with HP is potentially the most powerful method of detection of early pancreatic cancer. Although mutant (mt) K-ras can be detected in the pancreatic juice of most patients with pancreatic cancer, it is also present in patients with non-inherited chronic pancreatitis who do not progress to pancreatic cancer (at least in the short to medium term), as well as increasingly in the older population without pancreatic disease. Nevertheless, the presence of mt-K-ras may identify a genuinely higher-risk group, enabling additional diagnostic imaging and molecular resources to be focussed on such a group. What is clear is that prospective multi-centre studies, such as that being pursued by the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (EUROPAC), are essential for the development of an effective secondary screening programme for these patients.","DOI":"10.1159/000055852","ISSN":"1424-3903","note":"PMID: 12120229","journalAbbreviation":"Pancreatology","language":"eng","author":[{"family":"Wong","given":"T."},{"family":"Howes","given":"N."},{"family":"Threadgold","given":"J."},{"family":"Smart","given":"H. L."},{"family":"Lombard","given":"M. G."},{"family":"Gilmore","given":"I."},{"family":"Sutton","given":"R."},{"family":"Greenhalf","given":"W."},{"family":"Ellis","given":"I."},{"family":"Neoptolemos","given":"J. P."}],"issued":{"date-parts":[["2001"]]}}},{"id":"BbVydael/mRvlgSyN","uris":[""],"uri":[""],"itemData":{"id":212,"type":"article-journal","title":"New DNA Methylation Markers for Pancreatic Cancer: Discovery, Tissue Validation, and Pilot Testing in Pancreatic Juice","container-title":"Clinical Cancer Research: An Official Journal of the American Association for Cancer Research","page":"4473-4481","volume":"21","issue":"19","source":"PubMed","abstract":"PURPOSE: Discriminant markers for pancreatic cancer detection are needed. We sought to identify and validate methylated DNA markers for pancreatic cancer using next-generation sequencing unbiased by known targets.\nEXPERIMENTAL DESIGN: At a referral center, we conducted four sequential case-control studies: discovery, technical validation, biologic validation, and clinical piloting. Candidate markers were identified using variance-inflated logistic regression on reduced-representation bisulfite DNA sequencing results from matched pancreatic cancers, benign pancreas, and normal colon tissues. Markers were validated technically on replicate discovery study DNA and biologically on independent, matched, blinded tissues by methylation-specific PCR. Clinical testing of six methylation candidates and mutant KRAS was performed on secretin-stimulated pancreatic juice samples from 61 patients with pancreatic cancer, 22 with chronic pancreatitis, and 19 with normal pancreas on endoscopic ultrasound. Areas under receiver-operating characteristics curves (AUC) for markers were calculated.\nRESULTS: Sequencing identified >500 differentially hyper-methylated regions. On independent tissues, AUC on 19 selected markers ranged between 0.73 and 0.97. Pancreatic juice AUC values for CD1D, KCNK12, CLEC11A, NDRG4, IKZF1, PKRCB, and KRAS were 0.92*, 0.88, 0.85, 0.85, 0.84, 0.83, and 0.75, respectively, for pancreatic cancer compared with normal pancreas and 0.92*, 0.73, 0.76, 0.85*, 0.73, 0.77, and 0.62 for pancreatic cancer compared with chronic pancreatitis (*, P = 0.001 vs. KRAS).\nCONCLUSIONS: We identified and validated novel DNA methylation markers strongly associated with pancreatic cancer. On pilot testing in pancreatic juice, best markers (especially CD1D) highly discriminated pancreatic cases from controls.","DOI":"10.1158/1078-R-14-2469","ISSN":"1078-0432","note":"PMID: 26023084\nPMCID: PMC4592385","title-short":"New DNA Methylation Markers for Pancreatic Cancer","journalAbbreviation":"Clin. Cancer Res.","language":"eng","author":[{"family":"Kisiel","given":"John B."},{"family":"Raimondo","given":"Massimo"},{"family":"Taylor","given":"William R."},{"family":"Yab","given":"Tracy C."},{"family":"Mahoney","given":"Douglas W."},{"family":"Sun","given":"Zhifu"},{"family":"Middha","given":"Sumit"},{"family":"Baheti","given":"Saurabh"},{"family":"Zou","given":"Hongzhi"},{"family":"Smyrk","given":"Thomas C."},{"family":"Boardman","given":"Lisa A."},{"family":"Petersen","given":"Gloria M."},{"family":"Ahlquist","given":"David A."}],"issued":{"date-parts":[["2015",10,1]]}}},{"id":"BbVydael/nhO8TXJu","uris":[""],"uri":[""],"itemData":{"id":210,"type":"article-journal","title":"Next-Generation Sequencing Revealed TP53 Mutations to Be Malignant Marker for Intraductal Papillary Mucinous Neoplasms That Could Be Detected Using Pancreatic Juice","container-title":"Pancreas","page":"1281-1287","volume":"46","issue":"10","source":"PubMed","abstract":"OBJECTIVES: The aims of this study were to identify the genetic mutations associated with malignant intraductal papillary mucinous neoplasms (IPMNs) and evaluate the possibility of detecting mutations in pure pancreatic juice by next-generation sequencing.\nMETHODS: Resected tissues were collected from 50 patients with IPMN, and pure pancreatic juice samples were collected from 19 patients who had a resection. The extracted DNA was amplified by multiplex polymerase chain reaction targeting 52 cancer-related genes, including KRAS, GNAS, RNF43, and TP53; the mutations were then detected by next-generation sequencing and then analyzed for correlations with the clinicopathological characteristics.\nRESULTS: In the resected tissues, the most frequently detected mutations were in KRAS, GNAS, TP53, and RNF43, in 88%, 76%, 36%, and 30% of cases, respectively. Univariate and multivariate analyses revealed that only TP53 mutations were associated with malignant IPMNs (P = 0.023). In the pure pancreatic juice, TP53 mutations were detected in 5 of 10 resected samples with malignant IPMN and in 4 of 5 pancreatic juice samples with mutation in resected samples.\nCONCLUSIONS: From 52 cancer-related gene analysis, only TP53 mutation was associated with malignant IPMNs. TP53 mutation could also be detected in pure pancreatic juice, potentially making it a useful tool to diagnose malignant IPMNs preoperatively.","DOI":"10.1097/MPA.0000000000000931","ISSN":"1536-4828","note":"PMID: 28930868","journalAbbreviation":"Pancreas","language":"eng","author":[{"family":"Takano","given":"Shinichi"},{"family":"Fukasawa","given":"Mitsuharu"},{"family":"Kadokura","given":"Makoto"},{"family":"Shindo","given":"Hiroko"},{"family":"Takahashi","given":"Ei"},{"family":"Hirose","given":"Sumio"},{"family":"Maekawa","given":"Shinya"},{"family":"Mochizuki","given":"Kunio"},{"family":"Kawaida","given":"Hiromichi"},{"family":"Itakura","given":"Jun"},{"family":"Katoh","given":"Ryohei"},{"family":"Fujii","given":"Hideki"},{"family":"Sato","given":"Tadashi"},{"family":"Enomoto","given":"Nobuyuki"}],"issued":{"date-parts":[["2017",12]]}}},{"id":"BbVydael/o0zMPIwS","uris":[""],"uri":[""],"itemData":{"id":208,"type":"article-journal","title":"Molecular analysis to detect pancreatic ductal adenocarcinoma in high-risk groups","container-title":"Gastroenterology","page":"2124-2130","volume":"128","issue":"7","source":"PubMed","abstract":"BACKGROUND & AIMS: Screening of high-risk groups for pancreatic cancer has not been adopted because of concerns regarding specificity and sensitivity. Suitability of a combination of 3 novel molecular screening techniques was investigated.\nMETHODS: Pancreatic juice was extracted from 146 patients with pancreatic ductal adenocarcinoma, chronic pancreatitis, or biliary tract stones. p53 mutations were analyzed by using a modified yeast functional assay, K-ras status was analyzed using mutation-specific real-time PCR and the proportion of p16(INK4a) promoter methylation was estimated using comparative methylation-specific real-time PCR.\nRESULTS: p53 mutations were detected in 20 of 48 (42%) cancer cases, none of 49 controls, and 2 of 49 (4%) patients with pancreatitis. K-ras mutations were detected in 31 of 57 (54%) cancer patients, 13 of 61 (21%) controls, and 23 of 67 (34%) patients with pancreatitis. Twenty-six of 42 (62%) cancer patients had promoter methylation levels > 12%, compared with 3 of 24 (13%) controls, and 2 of 26 (8%) with pancreatitis. Mutations in p53 or high-level p16(INK4a) promoter methylation occurred in 29 of 36 (80%) patients with cancer, 3 of 24 (13%) controls, and 3 of 22 (13%) with pancreatitis. Three patients (8%) of 36 with cancer; 14 of 24 (58%) controls, and 13 of 22 (59%) patients with pancreatitis had no marker. The gallstone disease patients had a high rate of positive K-ras mutations, possibly reflecting the fact that they were not disease free.\nCONCLUSIONS: Combination molecular analysis increased the discrimination between patients with malignant and benign disease. This level of discrimination would allow patients in high-risk groups to be stratified from negligible risk to over 50% probability of an early cancer.","ISSN":"0016-5085","note":"PMID: 15940643","journalAbbreviation":"Gastroenterology","language":"eng","author":[{"family":"Yan","given":"Li"},{"family":"McFaul","given":"Christopher"},{"family":"Howes","given":"Nathan"},{"family":"Leslie","given":"Jane"},{"family":"Lancaster","given":"Gillian"},{"family":"Wong","given":"Theresa"},{"family":"Threadgold","given":"Jane"},{"family":"Evans","given":"Jonathan"},{"family":"Gilmore","given":"Ian"},{"family":"Smart","given":"Howard"},{"family":"Lombard","given":"Martin"},{"family":"Neoptolemos","given":"John"},{"family":"Greenhalf","given":"William"}],"issued":{"date-parts":[["2005",6]]}}},{"id":"BbVydael/8O2BsvBL","uris":[""],"uri":[""],"itemData":{"id":205,"type":"article-journal","title":"Clinical Impact of the KL-6 Concentration of Pancreatic Juice for Diagnosing Pancreatic Masses","container-title":"BioMed Research International","page":"528304","volume":"2015","source":"PubMed","abstract":"BACKGROUND AND AIM: Pancreatic juice cytology (PJC) is considered optimal for differentially diagnosing pancreatic masses, but the accuracy of PJC ranges from 46.7% to 93.0%. The aim of this study was to evaluate the clinical impact of measuring the KL-6 concentration of pancreatic juice for diagnosing pancreatic masses.\nMETHODS: PJC and the KL-6 concentration measurements of pancreatic juice were performed for 70 consecutive patients with pancreatic masses (39 malignancies and 31 benign).\nRESULTS: The average KL-6 concentration of pancreatic juice was significantly higher for pancreatic ductal adenocarcinomas (PDACs) (167.7 ± 396.1?U/mL) and intraductal papillary mucinous carcinomas (IPMCs) (86.9 ± 21.1?U/mL) than for pancreatic inflammatory lesions (17.5 ± 15.7?U/mL, P = 0.034) and intraductal papillary mucinous neoplasms (14.4 ± 2.0?U/mL, P = 0.026), respectively. When the cut-off level of the KL-6 concentration of pancreatic juice was 16?U/mL, the sensitivity, specificity, and accuracy of the KL-6 concentration of pancreatic juice alone were 79.5%, 64.5%, and 72.9%, respectively. Adding the KL-6 concentration of pancreatic juice to PJC when making a diagnosis caused the values of sensitivity and accuracy of PJC to increase by 15.3% (P = 0.025) and 8.5% (P = 0.048), respectively.\nCONCLUSIONS: The KL-6 concentration of pancreatic juice may be as useful as PJC for diagnosing PDACs.","DOI":"10.1155/2015/528304","ISSN":"2314-6141","note":"PMID: 26451373\nPMCID: PMC4584219","journalAbbreviation":"Biomed Res Int","language":"eng","author":[{"family":"Matsumoto","given":"Kazuya"},{"family":"Takeda","given":"Yohei"},{"family":"Harada","given":"Kenichi"},{"family":"Onoyama","given":"Takumi"},{"family":"Kawata","given":"Soichiro"},{"family":"Horie","given":"Yasushi"},{"family":"Sakamoto","given":"Teruhisa"},{"family":"Ueki","given":"Masaru"},{"family":"Miura","given":"Norimasa"},{"family":"Murawaki","given":"Yoshikazu"}],"issued":{"date-parts":[["2015"]]}}}],"schema":""} [65–69]. The role of these exams in FPC screening strategies must still be defined ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"MEQkS5dh","properties":{"formattedCitation":"\\super [68]\\nosupersub{}","plainCitation":"[68]","noteIndex":0},"citationItems":[{"id":"BbVydael/o0zMPIwS","uris":[""],"uri":[""],"itemData":{"id":208,"type":"article-journal","title":"Molecular analysis to detect pancreatic ductal adenocarcinoma in high-risk groups","container-title":"Gastroenterology","page":"2124-2130","volume":"128","issue":"7","source":"PubMed","abstract":"BACKGROUND & AIMS: Screening of high-risk groups for pancreatic cancer has not been adopted because of concerns regarding specificity and sensitivity. Suitability of a combination of 3 novel molecular screening techniques was investigated.\nMETHODS: Pancreatic juice was extracted from 146 patients with pancreatic ductal adenocarcinoma, chronic pancreatitis, or biliary tract stones. p53 mutations were analyzed by using a modified yeast functional assay, K-ras status was analyzed using mutation-specific real-time PCR and the proportion of p16(INK4a) promoter methylation was estimated using comparative methylation-specific real-time PCR.\nRESULTS: p53 mutations were detected in 20 of 48 (42%) cancer cases, none of 49 controls, and 2 of 49 (4%) patients with pancreatitis. K-ras mutations were detected in 31 of 57 (54%) cancer patients, 13 of 61 (21%) controls, and 23 of 67 (34%) patients with pancreatitis. Twenty-six of 42 (62%) cancer patients had promoter methylation levels > 12%, compared with 3 of 24 (13%) controls, and 2 of 26 (8%) with pancreatitis. Mutations in p53 or high-level p16(INK4a) promoter methylation occurred in 29 of 36 (80%) patients with cancer, 3 of 24 (13%) controls, and 3 of 22 (13%) with pancreatitis. Three patients (8%) of 36 with cancer; 14 of 24 (58%) controls, and 13 of 22 (59%) patients with pancreatitis had no marker. The gallstone disease patients had a high rate of positive K-ras mutations, possibly reflecting the fact that they were not disease free.\nCONCLUSIONS: Combination molecular analysis increased the discrimination between patients with malignant and benign disease. This level of discrimination would allow patients in high-risk groups to be stratified from negligible risk to over 50% probability of an early cancer.","ISSN":"0016-5085","note":"PMID: 15940643","journalAbbreviation":"Gastroenterology","language":"eng","author":[{"family":"Yan","given":"Li"},{"family":"McFaul","given":"Christopher"},{"family":"Howes","given":"Nathan"},{"family":"Leslie","given":"Jane"},{"family":"Lancaster","given":"Gillian"},{"family":"Wong","given":"Theresa"},{"family":"Threadgold","given":"Jane"},{"family":"Evans","given":"Jonathan"},{"family":"Gilmore","given":"Ian"},{"family":"Smart","given":"Howard"},{"family":"Lombard","given":"Martin"},{"family":"Neoptolemos","given":"John"},{"family":"Greenhalf","given":"William"}],"issued":{"date-parts":[["2005",6]]}}}],"schema":""} [68].Endoscopic ultrasound-guided fine needle aspiration and fine needle biopsyAnother advantage of EUS is that FNA or fine needle biopsy (FNB) can be performed in solid pancreatic masses to obtain tissue samples for histopathological characterization with a low risk of complications ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"yaRRw3BQ","properties":{"formattedCitation":"\\super [11,14,23,33,70]\\nosupersub{}","plainCitation":"[11,14,23,33,70]","noteIndex":0},"citationItems":[{"id":"BbVydael/iMJ7y1A2","uris":[""],"uri":[""],"itemData":{"id":33,"type":"article-journal","title":"Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma: a patient-level meta-analysis and proposition of the Beaujon score","container-title":"United European Gastroenterology Journal","page":"205064061882491","source":"Crossref","DOI":"10.1177/2050640618824910","ISSN":"2050-6406, 2050-6414","title-short":"Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma","language":"en","author":[{"family":"Mestier","given":"Louis","non-dropping-particle":"de"},{"family":"Muller","given":"Marie"},{"family":"Cros","given":"Jér?me"},{"family":"Vullierme","given":"Marie-Pierre"},{"family":"Vernerey","given":"Dewi"},{"family":"Maire","given":"Frédérique"},{"family":"Dokmak","given":"Safi"},{"family":"Rebours","given":"Vinciane"},{"family":"Sauvanet","given":"Alain"},{"family":"Lévy","given":"Philippe"},{"family":"Hammel","given":"Pascal"}],"issued":{"date-parts":[["2019",1,12]]}}},{"id":"BbVydael/L7ID64fl","uris":[""],"uri":[""],"itemData":{"id":61,"type":"article-journal","title":"Promising outcomes of screening for pancreatic cancer by genetic testing and endoscopic ultrasound","container-title":"Pancreas","page":"458-461","volume":"43","issue":"3","source":"PubMed","abstract":"OBJECTIVE: This study aimed to determine if screening patients based on certain cancer syndromes or family history criteria can lead to early detection of pancreatic cancer.\nMETHODS: This was a cohort study from 2008 to 2011 at a large tertiary referral center. A total of 30 patients met high-risk criteria after genetic counseling and were referred to a gastroenterologist for possible endoscopic ultrasound (EUS).\nRESULTS: Of the 30 patients, 16 underwent EUS. Subsequently, 3 patients had fine needle aspiration. Two patients had pancreatic adenocarcinoma, and 1 patient had an intraductal papillary mucinous neoplasm with low-grade dysplasia. The 2 patients with pancreatic adenocarcinoma both had breast cancer and BRCA2 mutations. The patient with the intraductal papillary mucinous neoplasm had Peutz-Jeghers syndrome. All 3 patients underwent surgery and have remained cancer free.\nCONCLUSIONS: Genetic risk assessment with EUS +/- fine needle aspiration in high-risk patients may lead to earlier detection of pancreatic cancer and potentially improve overall morbidity and mortality. Greater emphasis should be placed on screening patients for hereditary cancer syndromes that increase the risk of pancreatic cancer.","DOI":"10.1097/MPA.0000000000000052","ISSN":"1536-4828","note":"PMID: 24622079","journalAbbreviation":"Pancreas","language":"eng","author":[{"family":"Sud","given":"Anchal"},{"family":"Wham","given":"Deborah"},{"family":"Catalano","given":"Marc"},{"family":"Guda","given":"Nalini M."}],"issued":{"date-parts":[["2014",4]]}}},{"id":"BbVydael/NFPiCpG1","uris":[""],"uri":[""],"itemData":{"id":46,"type":"article-journal","title":"Screening for early pancreatic neoplasia in high-risk individuals: a prospective controlled study","container-title":"Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association","page":"766-781; quiz 665","volume":"4","issue":"6","source":"PubMed","abstract":"BACKGROUND & AIMS: Individuals with a strong family history of pancreatic cancer and persons with Peutz-Jeghers syndrome (PJS) have an increased risk for pancreatic cancer. This study screened for early pancreatic neoplasia and compared the pancreatic abnormalities in high-risk individuals and control subjects.\nMETHODS: High-risk individuals with PJS or a strong family history of pancreatic cancer were prospectively evaluated with baseline and 12-month computed tomography (CT) scan and endoscopic ultrasonography (EUS). If EUS was abnormal, EUS-fine-needle aspiration and endoscopic retrograde cholangiopancreatography (ERCP) were performed. Surgery was offered to patients with potentially neoplastic lesions. Radiologic findings and pathologic diagnoses were compared. Patients undergoing EUS and/or ERCP for benign non-pancreatic indications were concurrently enrolled as control subjects.\nRESULTS: Seventy-eight high-risk patients (72 from familial pancreatic cancer kindreds, 6 PJS) and 149 control patients were studied. To date, 8 patients with pancreatic neoplasia have been confirmed by surgery or fine-needle aspiration (10% yield of screening); 6 patients had 8 benign intraductal papillary mucinous neoplasms (IPMNs), 1 had an IPMN that progressed to invasive ductal adenocarcinoma, and 1 had pancreatic intraepithelial neoplasia. EUS and CT also diagnosed 3 patients with 5 extrapancreatic neoplasms. At EUS and ERCP abnormalities suggestive of chronic pancreatitis were more common in high-risk patients than in control subjects.\nCONCLUSIONS: Screening EUS and CT diagnosed significant asymptomatic pancreatic and extrapancreatic neoplasms in high-risk individuals. IPMN should be considered a part of the phenotype of familial pancreatic cancer. Abnormalities suggestive of chronic pancreatitis are identified more commonly at EUS and ERCP in high-risk individuals.","DOI":"10.1016/j.cgh.2006.02.005","ISSN":"1542-3565","note":"PMID: 16682259","title-short":"Screening for early pancreatic neoplasia in high-risk individuals","journalAbbreviation":"Clin. Gastroenterol. Hepatol.","language":"eng","author":[{"family":"Canto","given":"Marcia Irene"},{"family":"Goggins","given":"Michael"},{"family":"Hruban","given":"Ralph H."},{"family":"Petersen","given":"Gloria M."},{"family":"Giardiello","given":"Francis M."},{"family":"Yeo","given":"Charles"},{"family":"Fishman","given":"Elliott K."},{"family":"Brune","given":"Kieran"},{"family":"Axilbund","given":"Jennifer"},{"family":"Griffin","given":"Constance"},{"family":"Ali","given":"Syed"},{"family":"Richman","given":"Jeffrey"},{"family":"Jagannath","given":"Sanjay"},{"family":"Kantsevoy","given":"Sergey V."},{"family":"Kalloo","given":"Anthony N."}],"issued":{"date-parts":[["2006",6]]}}},{"id":"BbVydael/ujvJfaIr","uris":[""],"uri":[""],"itemData":{"id":52,"type":"article-journal","title":"Pancreatic cancer screening in a prospective cohort of high-risk patients: a comprehensive strategy of imaging and genetics","container-title":"Clinical Cancer Research: An Official Journal of the American Association for Cancer Research","page":"5028-5037","volume":"16","issue":"20","source":"PubMed","abstract":"PURPOSE: Pancreatic cancer is a virtually uniformly fatal disease. We aimed to determine if screening to identify curable neoplasms is effective when offered to patients at high risk.\nEXPERIMENTAL DESIGN: Patients at high risk of pancreatic cancer were prospectively enrolled into a screening program. Endoscopic ultrasound (EUS), magnetic resonance imaging (MRI), and genetic testing were offered by a multidisciplinary team according to each patient's risk.\nRESULTS: Fifty-one patients in 43 families were enrolled, with mean age of 52 years, 35% of whom were male. Of these patients, 31 underwent EUS and 33 MRI. EUS revealed two patients with pancreatic cancer (one resectable, one metastatic), five with intraductal papillary mucinous neoplasms (IPMN), seven with cysts, and six with parenchymal changes. Five had pancreatic surgery (one total pancreatectomy for pancreatic cancer, three distal and one central pancreatectomy for pancreatic intraepithelial neoplasia 2 and IPMN). A total of 24 (47%) had genetic testing (19 for BRCA1/2 mutations, 4 for CDKN2A, 1 for MLH1/MSH2) and 7 were positive for BRCA1/2 mutations. Four extrapancreatic neoplasms were found: two ovarian cancers on prophylactic total abdominal hysterectomy and bilateral salpingo-oophorectomy, one carcinoid, and one papillary thyroid carcinoma. Overall, 6 (12%) of the 51 patients had neoplastic lesions in the pancreas and 9 (18%) had neoplasms in any location. All were on the initial round of screening. All patients remain alive and without complications of screening.\nCONCLUSIONS: Pancreatic cancer screening for high-risk patients with a comprehensive strategy of imaging and genetics is effective and identifies curable neoplasms that can be resected. Ongoing study will better define who will benefit from screening and what screening strategy will be the most effective.","DOI":"10.1158/1078-R-09-3209","ISSN":"1078-0432","note":"PMID: 20876795","title-short":"Pancreatic cancer screening in a prospective cohort of high-risk patients","journalAbbreviation":"Clin. Cancer Res.","language":"eng","author":[{"family":"Verna","given":"Elizabeth C."},{"family":"Hwang","given":"Caroline"},{"family":"Stevens","given":"Peter D."},{"family":"Rotterdam","given":"Heidrun"},{"family":"Stavropoulos","given":"Stavros N."},{"family":"Sy","given":"Carolyn D."},{"family":"Prince","given":"Martin A."},{"family":"Chung","given":"Wendy K."},{"family":"Fine","given":"Robert L."},{"family":"Chabot","given":"John A."},{"family":"Frucht","given":"Harold"}],"issued":{"date-parts":[["2010",10,15]]}}},{"id":"BbVydael/ASLUPASS","uris":[""],"uri":[""],"itemData":{"id":119,"type":"article-journal","title":"Role of endoscopic ultrasound in the diagnosis of pancreatic cancer","container-title":"World Journal of Gastrointestinal Oncology","page":"360-368","volume":"6","issue":"9","source":"PubMed","abstract":"Endoscopic ultrasonography (EUS) with or without fine needle aspiration has become the main technique for evaluating pancreatobiliary disorders and has proved to have a higher diagnostic yield than positron emission tomography, computed tomography (CT) and transabdominal ultrasound for recognising early pancreatic tumors. As a diagnostic modality for pancreatic cancer, EUS has proved rates higher than 90%, especially for lesions less than 2-3 cm in size in which it reaches a sensitivity rate of 99% vs 55% for CT. Besides, EUS has a very high negative predictive value and thus EUS can reliably exclude pancreatic cancer. The complication rate of EUS is as low as 1.1%-3.0%. New technical developments such as elastography and the use of contrast agents have recently been applied to EUS, improving its diagnostic capability. EUS has been found to be superior to the recent multidetector CT for T staging with less risk of overstaying in comparison to both CT and magnetic resonance imaging, so that patients are not being ruled out of a potentially beneficial resection. The accuracy for N staging with EUS is 64%-82%. In unresectable cancers, EUS also plays a therapeutic role by means of treating oncological pain through celiac plexus block, biliary drainage in obstructive jaundice in patients where endoscopic retrograde cholangiopancreatography is not affordable and aiding radiotherapy and chemotherapy.","DOI":"10.4251/wjgo.v6.i9.360","ISSN":"1948-5204","note":"PMID: 25232461\nPMCID: PMC4163734","journalAbbreviation":"World J Gastrointest Oncol","language":"eng","author":[{"family":"Gonzalo-Marin","given":"Juana"},{"family":"Vila","given":"Juan Jose"},{"family":"Perez-Miranda","given":"Manuel"}],"issued":{"date-parts":[["2014",9,15]]}}}],"schema":""} [11,14,23,33,70]. The complication rate of?EUS-FNA?is approximately 2% ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"6FFIkO1Z","properties":{"formattedCitation":"\\super [70]\\nosupersub{}","plainCitation":"[70]","noteIndex":0},"citationItems":[{"id":"BbVydael/ASLUPASS","uris":[""],"uri":[""],"itemData":{"id":119,"type":"article-journal","title":"Role of endoscopic ultrasound in the diagnosis of pancreatic cancer","container-title":"World Journal of Gastrointestinal Oncology","page":"360-368","volume":"6","issue":"9","source":"PubMed","abstract":"Endoscopic ultrasonography (EUS) with or without fine needle aspiration has become the main technique for evaluating pancreatobiliary disorders and has proved to have a higher diagnostic yield than positron emission tomography, computed tomography (CT) and transabdominal ultrasound for recognising early pancreatic tumors. As a diagnostic modality for pancreatic cancer, EUS has proved rates higher than 90%, especially for lesions less than 2-3 cm in size in which it reaches a sensitivity rate of 99% vs 55% for CT. Besides, EUS has a very high negative predictive value and thus EUS can reliably exclude pancreatic cancer. The complication rate of EUS is as low as 1.1%-3.0%. New technical developments such as elastography and the use of contrast agents have recently been applied to EUS, improving its diagnostic capability. EUS has been found to be superior to the recent multidetector CT for T staging with less risk of overstaying in comparison to both CT and magnetic resonance imaging, so that patients are not being ruled out of a potentially beneficial resection. The accuracy for N staging with EUS is 64%-82%. In unresectable cancers, EUS also plays a therapeutic role by means of treating oncological pain through celiac plexus block, biliary drainage in obstructive jaundice in patients where endoscopic retrograde cholangiopancreatography is not affordable and aiding radiotherapy and chemotherapy.","DOI":"10.4251/wjgo.v6.i9.360","ISSN":"1948-5204","note":"PMID: 25232461\nPMCID: PMC4163734","journalAbbreviation":"World J Gastrointest Oncol","language":"eng","author":[{"family":"Gonzalo-Marin","given":"Juana"},{"family":"Vila","given":"Juan Jose"},{"family":"Perez-Miranda","given":"Manuel"}],"issued":{"date-parts":[["2014",9,15]]}}}],"schema":""} [70]. The sensitivity (84.3%), specificity (97%), and accuracy (84%) of EUS-FNA for solid pancreatic masses are high ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2lhUWNnF","properties":{"formattedCitation":"\\super [71]\\nosupersub{}","plainCitation":"[71]","noteIndex":0},"citationItems":[{"id":"BbVydael/ZLUj0e7m","uris":[""],"uri":[""],"itemData":{"id":158,"type":"article-journal","title":"Endoscopic ultrasound-guided fine needle aspiration biopsy of patients with suspected pancreatic cancer: diagnostic accuracy and acute and 30-day complications","container-title":"The American Journal of Gastroenterology","page":"2663-2668","volume":"98","issue":"12","source":"PubMed","abstract":"OBJECTIVES: The aims of this study were to evaluate the diagnostic accuracy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in patients with suspected pancreatic cancer, and to assess immediate, acute, and 30-day complications related to EUS-FNA.\nMETHODS: All patients with suspected pancreatic cancer were prospectively evaluated. A single gastroenterologist performed all EUS-FNAs in the presence of a cytopathologist. Immediate complications were evaluated in all patients. An experienced nurse called patients 24-72 h and 30 days after the procedure. Reference standard for the classification of the final diagnosis included: surgery (n = 48), clinical or imaging follow-up (n = 63), or death from the disease (n = 47).\nRESULTS: A total of 158 patients (mean age 62.3 yr) underwent EUS-FNA during the study period. The mean tumor size was 32 x 26 mm. The median number of passes was three (range one to 10). Of these patients, 44% had at least one failed attempt at tissue diagnosis before EUS-FNA. The sensitivity, specificity, PPV, NPV, and accuracy of EUS-FNA in solid pancreatic masses were 84.3%, 97%, 99%, 64%, and 84%, respectively. Immediate self-limited complications occurred in 10 of the 158 EUS-FNAs (6.3%). Of 90 patients contacted at 24-72 h, 78 patients (87%) responded. Of the 90 patients, 20 (22%) reported at least one symptom, all of which were minor except in three cases (one self-limited acute pancreatitis and two emergency room visits, one of which led to admission). In all, 83 patients were contacted at 30 days, and 82% responded. No additional or continued complications were reported.\nCONCLUSIONS: EUS-FNA is highly accurate in identifying patients with suspected pancreatic cancer, especially when other modalities have failed. Major complications after EUS-FNA are rare, and minor complications are similar to those reported for upper endoscopy. It seems that follow-up at 1 wk might capture all of the adverse events related to EUS-FNA.","DOI":"10.1111/j.1572-0241.2003.08666.x","ISSN":"0002-9270","note":"PMID: 14687813","title-short":"Endoscopic ultrasound-guided fine needle aspiration biopsy of patients with suspected pancreatic cancer","journalAbbreviation":"Am. J. Gastroenterol.","language":"eng","author":[{"family":"Eloubeidi","given":"Mohamad A."},{"family":"Chen","given":"Victor K."},{"family":"Eltoum","given":"Isam A."},{"family":"Jhala","given":"Darshana"},{"family":"Chhieng","given":"David C."},{"family":"Jhala","given":"Nirag"},{"family":"Vickers","given":"Selwyn M."},{"family":"Wilcox","given":"C. Mel"}],"issued":{"date-parts":[["2003",12]]}}}],"schema":""} [71]. However, the negative predictive value is low (64%) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"TMVXRbA7","properties":{"formattedCitation":"\\super [26,71]\\nosupersub{}","plainCitation":"[26,71]","noteIndex":0},"citationItems":[{"id":"BbVydael/w0k4vP4h","uris":[""],"uri":[""],"itemData":{"id":113,"type":"article-journal","title":"Methods and outcomes of screening for pancreatic adenocarcinoma in high-risk individuals","container-title":"World Journal of Gastrointestinal Endoscopy","page":"833-842","volume":"7","issue":"9","source":"PubMed","abstract":"Pancreatic ductal adenocarcinoma (PDAC) is a lethal neoplasia, for which secondary prevention (i.e., screening) is advisable for high-risk individuals with \"familiar pancreatic cancer\" and with other specific genetic syndromes (Peutz-Jeghers, p16, BRCA2, PALB and mismatch repair gene mutation carriers). There is limited evidence regarding the accuracy of screening tests, their acceptability, costs and availability, and agreement on whom to treat. Successful target of screening are small resectable PDAC, intraductal papillary mucinous neoplasms with high-grade dysplasia and advanced pancreatic intraepithelial neoplasia. Both magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS) are employed for screening, and the overall yield for pre-malignant or malignant pancreatic lesions is of about 20% with EUS and 14% with MRI/magnetic resonance colangiopancreatography. EUS performs better for solid and MRI for cystic lesions. However, only 2% of these detected lesions can be considered a successful target, and there are insufficient data demonstrating that resection of benign or low grade lesions improves survival. Many patients in the published studies therefore seemed to have received an overtreatment by undergoing surgery. It is crucial to better stratify the risk of malignancy individually, and to better define optimal screening intervals and methods either with computerized tools or molecular biomarkers, possibly in large multicentre studies. At the moment, screening should be carefully performed within research protocols at experienced centres, offering involved individuals medical and psychological advice.","DOI":"10.4253/wjge.v7.i9.833","ISSN":"1948-5190","note":"PMID: 26240684\nPMCID: PMC4515417","journalAbbreviation":"World J Gastrointest Endosc","language":"eng","author":[{"family":"Capurso","given":"Gabriele"},{"family":"Signoretti","given":"Marianna"},{"family":"Valente","given":"Roberto"},{"family":"Arnelo","given":"Urban"},{"family":"Lohr","given":"Matthias"},{"family":"Poley","given":"Jan-Werner"},{"family":"Delle Fave","given":"Gianfranco"},{"family":"Del Chiaro","given":"Marco"}],"issued":{"date-parts":[["2015",7,25]]}}},{"id":"BbVydael/ZLUj0e7m","uris":[""],"uri":[""],"itemData":{"id":158,"type":"article-journal","title":"Endoscopic ultrasound-guided fine needle aspiration biopsy of patients with suspected pancreatic cancer: diagnostic accuracy and acute and 30-day complications","container-title":"The American Journal of Gastroenterology","page":"2663-2668","volume":"98","issue":"12","source":"PubMed","abstract":"OBJECTIVES: The aims of this study were to evaluate the diagnostic accuracy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in patients with suspected pancreatic cancer, and to assess immediate, acute, and 30-day complications related to EUS-FNA.\nMETHODS: All patients with suspected pancreatic cancer were prospectively evaluated. A single gastroenterologist performed all EUS-FNAs in the presence of a cytopathologist. Immediate complications were evaluated in all patients. An experienced nurse called patients 24-72 h and 30 days after the procedure. Reference standard for the classification of the final diagnosis included: surgery (n = 48), clinical or imaging follow-up (n = 63), or death from the disease (n = 47).\nRESULTS: A total of 158 patients (mean age 62.3 yr) underwent EUS-FNA during the study period. The mean tumor size was 32 x 26 mm. The median number of passes was three (range one to 10). Of these patients, 44% had at least one failed attempt at tissue diagnosis before EUS-FNA. The sensitivity, specificity, PPV, NPV, and accuracy of EUS-FNA in solid pancreatic masses were 84.3%, 97%, 99%, 64%, and 84%, respectively. Immediate self-limited complications occurred in 10 of the 158 EUS-FNAs (6.3%). Of 90 patients contacted at 24-72 h, 78 patients (87%) responded. Of the 90 patients, 20 (22%) reported at least one symptom, all of which were minor except in three cases (one self-limited acute pancreatitis and two emergency room visits, one of which led to admission). In all, 83 patients were contacted at 30 days, and 82% responded. No additional or continued complications were reported.\nCONCLUSIONS: EUS-FNA is highly accurate in identifying patients with suspected pancreatic cancer, especially when other modalities have failed. Major complications after EUS-FNA are rare, and minor complications are similar to those reported for upper endoscopy. It seems that follow-up at 1 wk might capture all of the adverse events related to EUS-FNA.","DOI":"10.1111/j.1572-0241.2003.08666.x","ISSN":"0002-9270","note":"PMID: 14687813","title-short":"Endoscopic ultrasound-guided fine needle aspiration biopsy of patients with suspected pancreatic cancer","journalAbbreviation":"Am. J. Gastroenterol.","language":"eng","author":[{"family":"Eloubeidi","given":"Mohamad A."},{"family":"Chen","given":"Victor K."},{"family":"Eltoum","given":"Isam A."},{"family":"Jhala","given":"Darshana"},{"family":"Chhieng","given":"David C."},{"family":"Jhala","given":"Nirag"},{"family":"Vickers","given":"Selwyn M."},{"family":"Wilcox","given":"C. Mel"}],"issued":{"date-parts":[["2003",12]]}}}],"schema":""} [26,71], indicating that a negative FNA does not exclude the presence of a (pre)malignant lesion. Thus, in the presence of a solid pancreatic lesion with negative histological samples, FNA (or FNB) must be repeated in HRI, and prophylactic pancreatectomy should be discussed. The use of cutting needles for EUS-FNB should improve pancreatic histological samples ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"lbSlcrZL","properties":{"formattedCitation":"\\super [72]\\nosupersub{}","plainCitation":"[72]","noteIndex":0},"citationItems":[{"id":"BbVydael/6xIPEzpG","uris":[""],"uri":[""],"itemData":{"id":160,"type":"article-journal","title":"Evaluation of 22G fine-needle aspiration (FNA) versus fine-needle biopsy (FNB) for endoscopic ultrasound-guided sampling of pancreatic lesions: a prospective comparison study","container-title":"Surgical Endoscopy","page":"3533-3539","volume":"32","issue":"8","source":"PubMed","abstract":"BACKGROUND: To compare the diagnostic yield and safety of 22G endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) in the diagnosis of pancreatic solid lesions.\nMETHODS: Between April 2014 and September 2015, 36 patients with pancreatic solid lesions were included for endoscopic ultrasound test. Patients were randomly divided into two groups: EUS-FNA (n?=?18) and EUS-FNB (n?=?18). Each nidus was punctured three times (15?~?20 insertions for each puncture) with a 22G needle. The core specimens were analyzed, and the diagnostic yields of FNA and FNB were evaluated.\nRESULTS: The procedure success rate was 100% with no complications. Cytological and histological examinations found that the diagnostic yield of FNB and FNA were both 83.3%. To get a definitive diagnosis, FNB needed fewer punctures than FNA (1.11 vs. 1.83; P??<??0.05).\nCONCLUSIONS: 22G EUS-FNB is a safe and effective way to diagnose pancreatic solid lesions. FNB required a lower number of needle passes to achieve a diagnosis compared with FNA.","DOI":"10.1007/s00464-018-6075-6","ISSN":"1432-2218","note":"PMID: 29404729\nPMCID: PMC6061052","title-short":"Evaluation of 22G fine-needle aspiration (FNA) versus fine-needle biopsy (FNB) for endoscopic ultrasound-guided sampling of pancreatic lesions","journalAbbreviation":"Surg Endosc","language":"eng","author":[{"family":"Tian","given":"Li"},{"family":"Tang","given":"An-Liu"},{"family":"Zhang","given":"Lei"},{"family":"Liu","given":"Xiao-Wen"},{"family":"Li","given":"Jing-Bo"},{"family":"Wang","given":"Fen"},{"family":"Shen","given":"Shou-Rong"},{"family":"Wang","given":"Xiao-Yan"}],"issued":{"date-parts":[["2018",8]]}}}],"schema":""} [72]. In addition, EUS-FNA is associated with a non-negligible rate of false positives (2% in the literature, up to 33% in HRI, especially in patients with CPis). Thus, the diagnostic value of FNA may be limited in HRI screening ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"XK0qGELw","properties":{"formattedCitation":"\\super [11]\\nosupersub{}","plainCitation":"[11]","noteIndex":0},"citationItems":[{"id":"BbVydael/iMJ7y1A2","uris":[""],"uri":[""],"itemData":{"id":33,"type":"article-journal","title":"Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma: a patient-level meta-analysis and proposition of the Beaujon score","container-title":"United European Gastroenterology Journal","page":"205064061882491","source":"Crossref","DOI":"10.1177/2050640618824910","ISSN":"2050-6406, 2050-6414","title-short":"Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma","language":"en","author":[{"family":"Mestier","given":"Louis","non-dropping-particle":"de"},{"family":"Muller","given":"Marie"},{"family":"Cros","given":"Jér?me"},{"family":"Vullierme","given":"Marie-Pierre"},{"family":"Vernerey","given":"Dewi"},{"family":"Maire","given":"Frédérique"},{"family":"Dokmak","given":"Safi"},{"family":"Rebours","given":"Vinciane"},{"family":"Sauvanet","given":"Alain"},{"family":"Lévy","given":"Philippe"},{"family":"Hammel","given":"Pascal"}],"issued":{"date-parts":[["2019",1,12]]}}}],"schema":""} [11]. Improving the detection of high-grade PanIN in high-risk individualsThe theoretical risk of hereditary transmission of PC-predisposing genetic abnormalities is up to 50%. Hence, in the setting of FPC without a known predisposing gene mutation, approximately 50% of HRI undergo screening theoretically without predisposing genetic abnormalities. Thus, the detection of any cystic lesions or CPis is important in FPC-related HRI without identified mutations because it probably indicates that this subject carries the unidentified mutation and is hence at risk of PC.Most PC arise from PanIN lesions, with a delay of approximately ten years ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"BiAkgLwT","properties":{"formattedCitation":"\\super [22]\\nosupersub{}","plainCitation":"[22]","noteIndex":0},"citationItems":[{"id":"BbVydael/VeQTsQWK","uris":[""],"uri":[""],"itemData":{"id":351,"type":"article-journal","title":"Distant metastasis occurs late during the genetic evolution of pancreatic cancer","container-title":"Nature","page":"1114-1117","volume":"467","issue":"7319","source":"PubMed","abstract":"Metastasis, the dissemination and growth of neoplastic cells in an organ distinct from that in which they originated, is the most common cause of death in cancer patients. This is particularly true for pancreatic cancers, where most patients are diagnosed with metastatic disease and few show a sustained response to chemotherapy or radiation therapy. Whether the dismal prognosis of patients with pancreatic cancer compared to patients with other types of cancer is a result of late diagnosis or early dissemination of disease to distant organs is not known. Here we rely on data generated by sequencing the genomes of seven pancreatic cancer metastases to evaluate the clonal relationships among primary and metastatic cancers. We find that clonal populations that give rise to distant metastases are represented within the primary carcinoma, but these clones are genetically evolved from the original parental, non-metastatic clone. Thus, genetic heterogeneity of metastases reflects that within the primary carcinoma. A quantitative analysis of the timing of the genetic evolution of pancreatic cancer was performed, indicating at least a decade between the occurrence of the initiating mutation and the birth of the parental, non-metastatic founder cell. At least five more years are required for the acquisition of metastatic ability and patients die an average of two years thereafter. These data provide novel insights into the genetic features underlying pancreatic cancer progression and define a broad time window of opportunity for early detection to prevent deaths from metastatic disease.","DOI":"10.1038/nature09515","ISSN":"1476-4687","note":"PMID: 20981102\nPMCID: PMC3148940","journalAbbreviation":"Nature","language":"eng","author":[{"family":"Yachida","given":"Shinichi"},{"family":"Jones","given":"Si?n"},{"family":"Bozic","given":"Ivana"},{"family":"Antal","given":"Tibor"},{"family":"Leary","given":"Rebecca"},{"family":"Fu","given":"Baojin"},{"family":"Kamiyama","given":"Mihoko"},{"family":"Hruban","given":"Ralph H."},{"family":"Eshleman","given":"James R."},{"family":"Nowak","given":"Martin A."},{"family":"Velculescu","given":"Victor E."},{"family":"Kinzler","given":"Kenneth W."},{"family":"Vogelstein","given":"Bert"},{"family":"Iacobuzio-Donahue","given":"Christine A."}],"issued":{"date-parts":[["2010",10,28]]}}}],"schema":""} [22]. The challenge of screening is being able to propose surgery at the stage of high-grade PanINs. Some aspects of high-grade PanINs have been described with MRI and EUS, but these lesions lack specificity ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"mYi3Hv51","properties":{"formattedCitation":"\\super [23,51,73]\\nosupersub{}","plainCitation":"[23,51,73]","noteIndex":0},"citationItems":[{"id":"BbVydael/NFPiCpG1","uris":[""],"uri":[""],"itemData":{"id":46,"type":"article-journal","title":"Screening for early pancreatic neoplasia in high-risk individuals: a prospective controlled study","container-title":"Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association","page":"766-781; quiz 665","volume":"4","issue":"6","source":"PubMed","abstract":"BACKGROUND & AIMS: Individuals with a strong family history of pancreatic cancer and persons with Peutz-Jeghers syndrome (PJS) have an increased risk for pancreatic cancer. This study screened for early pancreatic neoplasia and compared the pancreatic abnormalities in high-risk individuals and control subjects.\nMETHODS: High-risk individuals with PJS or a strong family history of pancreatic cancer were prospectively evaluated with baseline and 12-month computed tomography (CT) scan and endoscopic ultrasonography (EUS). If EUS was abnormal, EUS-fine-needle aspiration and endoscopic retrograde cholangiopancreatography (ERCP) were performed. Surgery was offered to patients with potentially neoplastic lesions. Radiologic findings and pathologic diagnoses were compared. Patients undergoing EUS and/or ERCP for benign non-pancreatic indications were concurrently enrolled as control subjects.\nRESULTS: Seventy-eight high-risk patients (72 from familial pancreatic cancer kindreds, 6 PJS) and 149 control patients were studied. To date, 8 patients with pancreatic neoplasia have been confirmed by surgery or fine-needle aspiration (10% yield of screening); 6 patients had 8 benign intraductal papillary mucinous neoplasms (IPMNs), 1 had an IPMN that progressed to invasive ductal adenocarcinoma, and 1 had pancreatic intraepithelial neoplasia. EUS and CT also diagnosed 3 patients with 5 extrapancreatic neoplasms. At EUS and ERCP abnormalities suggestive of chronic pancreatitis were more common in high-risk patients than in control subjects.\nCONCLUSIONS: Screening EUS and CT diagnosed significant asymptomatic pancreatic and extrapancreatic neoplasms in high-risk individuals. IPMN should be considered a part of the phenotype of familial pancreatic cancer. Abnormalities suggestive of chronic pancreatitis are identified more commonly at EUS and ERCP in high-risk individuals.","DOI":"10.1016/j.cgh.2006.02.005","ISSN":"1542-3565","note":"PMID: 16682259","title-short":"Screening for early pancreatic neoplasia in high-risk individuals","journalAbbreviation":"Clin. Gastroenterol. Hepatol.","language":"eng","author":[{"family":"Canto","given":"Marcia Irene"},{"family":"Goggins","given":"Michael"},{"family":"Hruban","given":"Ralph H."},{"family":"Petersen","given":"Gloria M."},{"family":"Giardiello","given":"Francis M."},{"family":"Yeo","given":"Charles"},{"family":"Fishman","given":"Elliott K."},{"family":"Brune","given":"Kieran"},{"family":"Axilbund","given":"Jennifer"},{"family":"Griffin","given":"Constance"},{"family":"Ali","given":"Syed"},{"family":"Richman","given":"Jeffrey"},{"family":"Jagannath","given":"Sanjay"},{"family":"Kantsevoy","given":"Sergey V."},{"family":"Kalloo","given":"Anthony N."}],"issued":{"date-parts":[["2006",6]]}}},{"id":"BbVydael/qbQx1zWu","uris":[""],"uri":[""],"itemData":{"id":77,"type":"article-journal","title":"Multifocal neoplastic precursor lesions associated with lobular atrophy of the pancreas in patients having a strong family history of pancreatic cancer","container-title":"The American Journal of Surgical Pathology","page":"1067-1076","volume":"30","issue":"9","source":"PubMed","abstract":"We screened 116 patients with a strong family history of pancreatic cancer using a combination of endoscopic ultrasound and computed tomography. Ten of these patients underwent surgical resection at our institution, providing an opportunity to define the morphology of pancreatic precursor lesions in patients with a strong family history of pancreatic cancer. Eight of the 10 pancreata were available and these were entirely submitted for histologic examination. The number of pancreatic intraepithelial neoplasia (PanIN) lesions and intraductal papillary mucinous neoplasms (IPMNs) were compared with age-matched controls. Parenchymal changes were defined. Selected precursor neoplasms from 6 pancreata were microdissected and analyzed for KRAS gene mutations. PanINs were significantly more common in the 8 cases (mean of 10.7% of the duct profiles, range 1.0% to 27.3%) than in the controls (mean 1.9%, range 0% to 9.2%, P<0.01). Different KRAS gene mutations were identified in separately microdissected precursor lesions in 2 of 6 cases. IPMNs were identified in 4 of the 8 cases, including 2 pancreata each having 2 distinct IPMNs. Both the IPMNs and the PanINs, even the low-grade PanIN-1 lesions, were associated with lobular parenchymal atrophy. Some individuals with a strong family history of pancreatic cancer develop multifocal, noninvasive epithelial precursor lesions of the pancreas. PanINs and IPMNs produce obstructive lobular atrophy, and this atrophy is likely the source of the chronic pancreatitis-like changes seen in these patients. The multifocal nature of familial pancreatic neoplasia suggests that surveillance of these patients is warranted after partial pancreatectomy.","DOI":"pas.0000213265.84725.0b","ISSN":"0147-5185","note":"PMID: 16931950\nPMCID: PMC2746409","journalAbbreviation":"Am. J. Surg. Pathol.","language":"eng","author":[{"family":"Brune","given":"Kieran"},{"family":"Abe","given":"Tadayoshi"},{"family":"Canto","given":"Marcia"},{"family":"O'Malley","given":"Lauren"},{"family":"Klein","given":"Alison P."},{"family":"Maitra","given":"Anirban"},{"family":"Volkan Adsay","given":"N."},{"family":"Fishman","given":"Elliot K."},{"family":"Cameron","given":"John L."},{"family":"Yeo","given":"Charles J."},{"family":"Kern","given":"Scott E."},{"family":"Goggins","given":"Michael"},{"family":"Hruban","given":"Ralph H."}],"issued":{"date-parts":[["2006",9]]}}},{"id":"BbVydael/1l2sN0tX","uris":[""],"uri":[""],"itemData":{"id":356,"type":"article-journal","title":"Non-branched microcysts of the pancreas on MR imaging of patients with pancreatic tumors who had pancreatectomy may predict the presence of pancreatic intraepithelial neoplasia (PanIN): a preliminary study","container-title":"European Radiology","source":"PubMed","abstract":"PURPOSE: To evaluate whether pancreatic parenchymal abnormalities on magnetic resonance imaging (MRI) are associated with pancreatic intraepithelial neoplasia (PanIN) on histology.\nMATERIALS AND METHODS: Retrospective study approved by institutional review board. One hundred patients (48 men, 52 women; mean age, 53.2?±?16.29 [SD]) underwent MRI before pancreatectomy for pancreatic tumors analyzed by two independent observers blinded to histopathological results for the presence of non-communicating microcysts and pancreatic atrophy (global or focal) beside tumors. MRI findings were compared to histopathological findings of resected specimens. Interobserver agreement was calculated. The association between parenchymal abnormalities and presence of PanIN was assessed by uni- and multivariate analyses.\nRESULTS: PanIN was present in 65/100 patients (65%). The presence of microcysts on MRI had a sensitivity of 52.3% (34/65 [95%CI, 51.92-52.70%]), a specificity of 77.1% (27/35 [95%CI, 76.70-77.59]), and accuracy of 61% (61/100 95%CI [50.7-70.6]) for the diagnosis of PanIN while global atrophy had a sensitivity of 24.6% (16/6 [95%CI, 24.28-24.95]) and a specificity of 97.1% (34/35 [95%CI, 96.97-97.32%]). In multivariate analysis, the presence of microcysts (OR, 3.37 [95%CI, 1.3-8.76]) (p?=?0.0127) and global atrophy (OR, 9.79 [95%CI, 1.21-79.129]) (p?=?0.0324) were identified as independent predictors of the presence of PanIN. The combination of these two findings was observed in 10/65 PanIN patients and not in patients without PanIN (p?=?0.013 with an OR of infinity [95%CI, 1.3-infinity]) and was not discriminant for PanIN-3 and lower grade (p?=?0.22). Interobserver agreement for the presence of microcysts was excellent (kappa?=?0.92), and for the presence of global atrophy, it was good (kappa?=?0.73).\nCONCLUSION: The presence of non-communicating microcysts on pre-operative MRI can be a significant predictor of PanIN in patients with pancreatic tumors.\nKEY POINTS: ? In patients with pancreatic tumors who had partial pancreatectomy, MR non-communicating pancreatic microcysts have a 52.3% sensitivity, a 77.1% specificity, and a 61% accuracy for the presence of PanIN with univariate and with an odds ratio of 3.37 with multivariate analyses. ? The association of global atrophy and non-communicating microcysts increases the predictive risk of PanIN.","DOI":"10.1007/s00330-019-06154-3","ISSN":"1432-1084","note":"PMID: 30972547","title-short":"Non-branched microcysts of the pancreas on MR imaging of patients with pancreatic tumors who had pancreatectomy may predict the presence of pancreatic intraepithelial neoplasia (PanIN)","journalAbbreviation":"Eur Radiol","language":"eng","author":[{"family":"Vullierme","given":"Marie-Pierre"},{"family":"Menassa","given":"Lina"},{"family":"Couvelard","given":"Anne"},{"family":"Rebours","given":"Vinciane"},{"family":"Maire","given":"Frédérique"},{"family":"Ibrahim","given":"Tony"},{"family":"Cros","given":"Jerome"},{"family":"Ruszniewski","given":"Philippe"},{"family":"Sauvanet","given":"Alain"},{"family":"Levy","given":"Philippe"},{"family":"Soyer","given":"Philippe"},{"family":"Vilgrain","given":"Valerie"}],"issued":{"date-parts":[["2019",4,10]]}}}],"schema":""} [23,51,73]. Our group and others previously reported that CPis (microcysts and/or hyperechoic foci of fibrosis) visualized at EUS were associated with PanIN (in up to 83% of cases) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"NiSIZZl4","properties":{"formattedCitation":"\\super [51,54,74]\\nosupersub{}","plainCitation":"[51,54,74]","noteIndex":0},"citationItems":[{"id":"BbVydael/qbQx1zWu","uris":[""],"uri":[""],"itemData":{"id":77,"type":"article-journal","title":"Multifocal neoplastic precursor lesions associated with lobular atrophy of the pancreas in patients having a strong family history of pancreatic cancer","container-title":"The American Journal of Surgical Pathology","page":"1067-1076","volume":"30","issue":"9","source":"PubMed","abstract":"We screened 116 patients with a strong family history of pancreatic cancer using a combination of endoscopic ultrasound and computed tomography. Ten of these patients underwent surgical resection at our institution, providing an opportunity to define the morphology of pancreatic precursor lesions in patients with a strong family history of pancreatic cancer. Eight of the 10 pancreata were available and these were entirely submitted for histologic examination. The number of pancreatic intraepithelial neoplasia (PanIN) lesions and intraductal papillary mucinous neoplasms (IPMNs) were compared with age-matched controls. Parenchymal changes were defined. Selected precursor neoplasms from 6 pancreata were microdissected and analyzed for KRAS gene mutations. PanINs were significantly more common in the 8 cases (mean of 10.7% of the duct profiles, range 1.0% to 27.3%) than in the controls (mean 1.9%, range 0% to 9.2%, P<0.01). Different KRAS gene mutations were identified in separately microdissected precursor lesions in 2 of 6 cases. IPMNs were identified in 4 of the 8 cases, including 2 pancreata each having 2 distinct IPMNs. Both the IPMNs and the PanINs, even the low-grade PanIN-1 lesions, were associated with lobular parenchymal atrophy. Some individuals with a strong family history of pancreatic cancer develop multifocal, noninvasive epithelial precursor lesions of the pancreas. PanINs and IPMNs produce obstructive lobular atrophy, and this atrophy is likely the source of the chronic pancreatitis-like changes seen in these patients. The multifocal nature of familial pancreatic neoplasia suggests that surveillance of these patients is warranted after partial pancreatectomy.","DOI":"pas.0000213265.84725.0b","ISSN":"0147-5185","note":"PMID: 16931950\nPMCID: PMC2746409","journalAbbreviation":"Am. J. Surg. Pathol.","language":"eng","author":[{"family":"Brune","given":"Kieran"},{"family":"Abe","given":"Tadayoshi"},{"family":"Canto","given":"Marcia"},{"family":"O'Malley","given":"Lauren"},{"family":"Klein","given":"Alison P."},{"family":"Maitra","given":"Anirban"},{"family":"Volkan Adsay","given":"N."},{"family":"Fishman","given":"Elliot K."},{"family":"Cameron","given":"John L."},{"family":"Yeo","given":"Charles J."},{"family":"Kern","given":"Scott E."},{"family":"Goggins","given":"Michael"},{"family":"Hruban","given":"Ralph H."}],"issued":{"date-parts":[["2006",9]]}}},{"id":"BbVydael/0noAA4jF","uris":[""],"uri":[""],"itemData":{"id":42,"type":"article-journal","title":"Pancreatic intraepithelial neoplasia in patients with intraductal papillary mucinous neoplasms: the interest of endoscopic ultrasonography","container-title":"Pancreas","page":"1262-1266","volume":"42","issue":"8","source":"PubMed","abstract":"OBJECTIVES: Intraductal papillary mucinous neoplasms (IPMNs) and pancreatic intraepithelial neoplasia (PanIN) are both precancerous lesions. Papillary mucinous neoplasms have been described in patients with IPMN, but their relationship is still poorly understood. The aims of this study were to look for PanIN lesions in patients operated on for IPMN and to search for correlations between endoscopic ultrasonography(EUS) features and pathologic findings.\nMETHODS: Endoscopic ultrasonography was preoperatively performed in all patients with IPMN consecutively operated on in our center. Endoscopic ultrasonography features were prospectively compared with pathologic data from surgical specimen.\nRESULTS: Forty patients underwent resection for benign (52.5%) or malignant (47.5%) IPMN. Pancreatic intraepithelial neoplasia lesions were observed in 78% of cases (PanIN-3 in 19% of patients). PanIN-3 lesions were observed in 11% and 26% of patients with benign and malignant IPMN, respectively. Endoscopic ultrasonography changes(microcysts and/or hyperechoic foci) corresponded to PanIN lesions in 83% of cases. Endoscopic ultrasonography detected 69% of patients with PanIN lesions and 57% of those with panIN-3 lesions.\nCONCLUSIONS: Pancreatic intraepithelial neoplasia lesions are very frequently associated with IPMN, and 19% of patients with IPMN had PanIN-3 lesions. In two thirds of patients, EUS can detect minimal changes in the pancreas corresponding to PanIN lesions.","DOI":"10.1097/01.mpa.0000437639.38383.41","ISSN":"1536-4828","note":"PMID: 24152960","title-short":"Pancreatic intraepithelial neoplasia in patients with intraductal papillary mucinous neoplasms","journalAbbreviation":"Pancreas","language":"eng","author":[{"family":"Maire","given":"Frédérique"},{"family":"Couvelard","given":"Anne"},{"family":"Palazzo","given":"Laurent"},{"family":"Aubert","given":"Alain"},{"family":"Vullierme","given":"Marie-Pierre"},{"family":"Rebours","given":"Vinciane"},{"family":"Hammel","given":"Pascal"},{"family":"Sauvanet","given":"Alain"},{"family":"Levy","given":"Philippe"},{"family":"Ruszniewski","given":"Philippe"}],"issued":{"date-parts":[["2013",11]]}}},{"id":"BbVydael/GFZYk5WI","uris":[""],"uri":[""],"itemData":{"id":360,"type":"article-journal","title":"Can endoscopic ultrasound predict pancreatic intraepithelial neoplasia lesions in chronic pancreatitis?: a retrospective study of pathologic correlation","container-title":"Pancreas","page":"849-854","volume":"43","issue":"6","source":"PubMed","abstract":"OBJECTIVE: This study aimed to evaluate associations between endoscopic ultrasound (EUS) criteria for chronic pancreatitis (CP) and coexisting pancreatic intraepithelial neoplasia (PanIN) lesions.\nMETHODS: Patients with known or suspected CP who underwent pancreatic resection within a year of EUS were selected. Histology slides and EUS images were reviewed for evidence of pancreatic fibrosis.\nRESULTS: Ninety-seven (51 men; mean age, 53 [12] years) underwent EUS within a 1 year or less of EUS. Pancreatic intraepithelial neoplasia lesions were found in 84 (87%) patients. Pancreatic intraepithelial neoplasia 1, 2, and 3 lesions were seen in 71 (83%), 10 (14%), and 1 (2%), respectively. Two patients had more than 1 PanIN grade (one had PanIN 1 and 2 and the other had PanIN 1 and 3). The mean number of EUS criteria for PanIN 1, 2, and 3 lesions were 3.9, 4.5, and 5.5, respectively. The odds ratio for the association between PanIN 2 and hyperechoic foci without shadowing in the pancreas head was 8.5 (P = 0.05). The odds ratio for the association between PanIN 2 and lobularity with honeycombing was 2.7 (P = ns). Advanced PanIN lesions had greater than or equal to 4 EUS criteria for CP.\nCONCLUSIONS: Pancreatic intraepithelial neoplasia lesions were highly prevalent in CP resections. Increasing PanIN grade is observed with increasing fibrosis score and increasing number of EUS criteria for CP.","DOI":"10.1097/MPA.0000000000000142","ISSN":"1536-4828","note":"PMID: 24826885","title-short":"Can endoscopic ultrasound predict pancreatic intraepithelial neoplasia lesions in chronic pancreatitis?","journalAbbreviation":"Pancreas","language":"eng","author":[{"family":"LeBlanc","given":"Julia Kim"},{"family":"Chen","given":"Jey-Hsin"},{"family":"Al-Haddad","given":"Mohammad"},{"family":"Luz","given":"Leticia"},{"family":"McHenry","given":"Lee"},{"family":"Sherman","given":"Stuart"},{"family":"Juan","given":"Michelle"},{"family":"Dewitt","given":"John"}],"issued":{"date-parts":[["2014",8]]}}}],"schema":""} [51,54,74]. In an American study, the odds ratio for the association between intermediate-grade PanIN and hyperechoic foci without shadowing in the pancreas head was 8.5 (P = 0.05) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"22CQ6P8J","properties":{"formattedCitation":"\\super [74]\\nosupersub{}","plainCitation":"[74]","noteIndex":0},"citationItems":[{"id":"BbVydael/GFZYk5WI","uris":[""],"uri":[""],"itemData":{"id":360,"type":"article-journal","title":"Can endoscopic ultrasound predict pancreatic intraepithelial neoplasia lesions in chronic pancreatitis?: a retrospective study of pathologic correlation","container-title":"Pancreas","page":"849-854","volume":"43","issue":"6","source":"PubMed","abstract":"OBJECTIVE: This study aimed to evaluate associations between endoscopic ultrasound (EUS) criteria for chronic pancreatitis (CP) and coexisting pancreatic intraepithelial neoplasia (PanIN) lesions.\nMETHODS: Patients with known or suspected CP who underwent pancreatic resection within a year of EUS were selected. Histology slides and EUS images were reviewed for evidence of pancreatic fibrosis.\nRESULTS: Ninety-seven (51 men; mean age, 53 [12] years) underwent EUS within a 1 year or less of EUS. Pancreatic intraepithelial neoplasia lesions were found in 84 (87%) patients. Pancreatic intraepithelial neoplasia 1, 2, and 3 lesions were seen in 71 (83%), 10 (14%), and 1 (2%), respectively. Two patients had more than 1 PanIN grade (one had PanIN 1 and 2 and the other had PanIN 1 and 3). The mean number of EUS criteria for PanIN 1, 2, and 3 lesions were 3.9, 4.5, and 5.5, respectively. The odds ratio for the association between PanIN 2 and hyperechoic foci without shadowing in the pancreas head was 8.5 (P = 0.05). The odds ratio for the association between PanIN 2 and lobularity with honeycombing was 2.7 (P = ns). Advanced PanIN lesions had greater than or equal to 4 EUS criteria for CP.\nCONCLUSIONS: Pancreatic intraepithelial neoplasia lesions were highly prevalent in CP resections. Increasing PanIN grade is observed with increasing fibrosis score and increasing number of EUS criteria for CP.","DOI":"10.1097/MPA.0000000000000142","ISSN":"1536-4828","note":"PMID: 24826885","title-short":"Can endoscopic ultrasound predict pancreatic intraepithelial neoplasia lesions in chronic pancreatitis?","journalAbbreviation":"Pancreas","language":"eng","author":[{"family":"LeBlanc","given":"Julia Kim"},{"family":"Chen","given":"Jey-Hsin"},{"family":"Al-Haddad","given":"Mohammad"},{"family":"Luz","given":"Leticia"},{"family":"McHenry","given":"Lee"},{"family":"Sherman","given":"Stuart"},{"family":"Juan","given":"Michelle"},{"family":"Dewitt","given":"John"}],"issued":{"date-parts":[["2014",8]]}}}],"schema":""} [74]. This aspect would concern approximately 70% of HRI ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"Z9GVDSet","properties":{"formattedCitation":"\\super [12,23]\\nosupersub{}","plainCitation":"[12,23]","noteIndex":0},"citationItems":[{"id":"BbVydael/Y8fwuXm1","uris":[""],"uri":[""],"itemData":{"id":44,"type":"article-journal","title":"Screening for pancreatic neoplasia in high-risk individuals: an EUS-based approach","container-title":"Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association","page":"606-621","volume":"2","issue":"7","source":"PubMed","abstract":"BACKGROUND & AIMS: Relatives of patients with pancreatic cancer and persons with certain inherited syndromes are at increased risk for developing pancreatic cancer. We prospectively evaluated the feasibility of screening for pancreatic neoplasia in high-risk individuals.\nMETHODS: Individuals from familial pancreatic cancer kindreds and a patient with Peutz-Jeghers syndrome underwent screening endoscopic ultrasound (EUS). If the EUS was abnormal, EUS-guided fine-needle aspiration, endoscopic retrograde cholangiopancreatography (ERCP), and spiral computed tomography (CT) were performed. Patients with abnormalities suggesting neoplasia had surgery.\nRESULTS: Thirty-eight patients were studied; 31 (mean age, 58 yr; 42% men) from kindreds with > or =3 affected with pancreatic cancer; 6 from kindreds with 2 affected relatives, 1 was a patient with Peutz-Jeghers syndrome. None had symptoms referable to the pancreas or suggestive of malignancy. Six pancreatic masses were found by EUS: 1 invasive ductal adenocarcinoma, 1 benign intraductal papillary mucinous neoplasm, 2 serous cystadenomas, and 2 nonneoplastic masses. Hence, the diagnostic yield for detecting clinically significant pancreatic neoplasms was 5.3% (2 of 38). The 1 patient with pancreatic cancer was treated and still is alive and disease-free >5 years after surgery. EUS changes similar to those associated with chronic pancreatitis were found, which were more common in patients with a history of regular alcohol intake (P = 0.02), but also occurred in patients who did not consume alcohol. Screening also led to a new diagnosis and treatment of symptomatic upper-gastrointestinal conditions in 18.4% of patients.\nCONCLUSIONS: EUS-based screening of asymptomatic high-risk individuals can detect prevalent resectable pancreatic neoplasia but false-positive diagnoses also occur.","ISSN":"1542-3565","note":"PMID: 15224285","title-short":"Screening for pancreatic neoplasia in high-risk individuals","journalAbbreviation":"Clin. Gastroenterol. Hepatol.","language":"eng","author":[{"family":"Canto","given":"Marcia Irene"},{"family":"Goggins","given":"Michael"},{"family":"Yeo","given":"Charles J."},{"family":"Griffin","given":"Constance"},{"family":"Axilbund","given":"Jennifer E."},{"family":"Brune","given":"Kieran"},{"family":"Ali","given":"Syed Z."},{"family":"Jagannath","given":"Sanjay"},{"family":"Petersen","given":"Gloria M."},{"family":"Fishman","given":"Elliot K."},{"family":"Piantadosi","given":"Steven"},{"family":"Giardiello","given":"Francis M."},{"family":"Hruban","given":"Ralph H."}],"issued":{"date-parts":[["2004",7]]}}},{"id":"BbVydael/NFPiCpG1","uris":[""],"uri":[""],"itemData":{"id":46,"type":"article-journal","title":"Screening for early pancreatic neoplasia in high-risk individuals: a prospective controlled study","container-title":"Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association","page":"766-781; quiz 665","volume":"4","issue":"6","source":"PubMed","abstract":"BACKGROUND & AIMS: Individuals with a strong family history of pancreatic cancer and persons with Peutz-Jeghers syndrome (PJS) have an increased risk for pancreatic cancer. This study screened for early pancreatic neoplasia and compared the pancreatic abnormalities in high-risk individuals and control subjects.\nMETHODS: High-risk individuals with PJS or a strong family history of pancreatic cancer were prospectively evaluated with baseline and 12-month computed tomography (CT) scan and endoscopic ultrasonography (EUS). If EUS was abnormal, EUS-fine-needle aspiration and endoscopic retrograde cholangiopancreatography (ERCP) were performed. Surgery was offered to patients with potentially neoplastic lesions. Radiologic findings and pathologic diagnoses were compared. Patients undergoing EUS and/or ERCP for benign non-pancreatic indications were concurrently enrolled as control subjects.\nRESULTS: Seventy-eight high-risk patients (72 from familial pancreatic cancer kindreds, 6 PJS) and 149 control patients were studied. To date, 8 patients with pancreatic neoplasia have been confirmed by surgery or fine-needle aspiration (10% yield of screening); 6 patients had 8 benign intraductal papillary mucinous neoplasms (IPMNs), 1 had an IPMN that progressed to invasive ductal adenocarcinoma, and 1 had pancreatic intraepithelial neoplasia. EUS and CT also diagnosed 3 patients with 5 extrapancreatic neoplasms. At EUS and ERCP abnormalities suggestive of chronic pancreatitis were more common in high-risk patients than in control subjects.\nCONCLUSIONS: Screening EUS and CT diagnosed significant asymptomatic pancreatic and extrapancreatic neoplasms in high-risk individuals. IPMN should be considered a part of the phenotype of familial pancreatic cancer. Abnormalities suggestive of chronic pancreatitis are identified more commonly at EUS and ERCP in high-risk individuals.","DOI":"10.1016/j.cgh.2006.02.005","ISSN":"1542-3565","note":"PMID: 16682259","title-short":"Screening for early pancreatic neoplasia in high-risk individuals","journalAbbreviation":"Clin. Gastroenterol. Hepatol.","language":"eng","author":[{"family":"Canto","given":"Marcia Irene"},{"family":"Goggins","given":"Michael"},{"family":"Hruban","given":"Ralph H."},{"family":"Petersen","given":"Gloria M."},{"family":"Giardiello","given":"Francis M."},{"family":"Yeo","given":"Charles"},{"family":"Fishman","given":"Elliott K."},{"family":"Brune","given":"Kieran"},{"family":"Axilbund","given":"Jennifer"},{"family":"Griffin","given":"Constance"},{"family":"Ali","given":"Syed"},{"family":"Richman","given":"Jeffrey"},{"family":"Jagannath","given":"Sanjay"},{"family":"Kantsevoy","given":"Sergey V."},{"family":"Kalloo","given":"Anthony N."}],"issued":{"date-parts":[["2006",6]]}}}],"schema":""} [12,23]. However, the assessment of such abnormalities might suffer from a lack of recognition, and the correlation between EUS aspect and pathology should be assessed in a large series of HRI ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"XbGmgnQE","properties":{"formattedCitation":"\\super [28,60]\\nosupersub{}","plainCitation":"[28,60]","noteIndex":0},"citationItems":[{"id":"BbVydael/VywnNPwr","uris":[""],"uri":[""],"itemData":{"id":140,"type":"article-journal","title":"Interobserver agreement for EUS findings in familial pancreatic-cancer kindreds","container-title":"Gastrointestinal Endoscopy","page":"62-67","volume":"66","issue":"1","source":"PubMed","abstract":"BACKGROUND: EUS is a promising modality for pancreatic-cancer screening in high-risk persons, including familial pancreatic-cancer (FPC) kindreds.\nOBJECTIVE: To assess interobserver agreement for interpretation of EUS in persons at high risk for pancreatic cancer.\nDESIGN: Seventeen expert endosonographers blinded to patients' clinical history rated a \"training set\" of pancreatic EUS video clips for the presence of a normal examination, masses, cysts, and features of chronic pancreatitis. Clips included high-risk persons and controls (normal and various pancreatic diseases). The endosonographers then participated in a workshop on EUS findings in high-risk persons and drafted a consensus statement. Three months later, they blindly rated a \"test set\" composed of the same video clips.\nMAIN OUTCOME MEASUREMENTS: Interobserver agreement at baseline (training set) and after a consensus process (test set).\nRESULTS: For the training set, interobserver agreement was good (kappa>or=0.4) for the presence of cysts and was fair to poor for all other rated EUS features and diagnosis of normal. There was no overall improvement in the test set. In both the training and test sets, agreement was worse for clips from FPC kindreds (kappa>or=0.4 for cysts and <0.4 for all other features) than for controls (kappa>or=0.4 for normal, cysts, masses, echogenic strands, and lobularity).\nLIMITATIONS: Video clips were not of identical image quality and duration as a clinical EUS examination.\nCONCLUSIONS: There was fair to poor interobserver agreement for the interpretation of pancreatic EUS video clips from members of FPC kindreds. Agreement was not improved by a consensus process.","DOI":"10.1016/j.gie.2006.09.018","ISSN":"0016-5107","note":"PMID: 17382940","journalAbbreviation":"Gastrointest. Endosc.","language":"eng","author":[{"family":"Topazian","given":"Mark"},{"family":"Enders","given":"Felicity"},{"family":"Kimmey","given":"Michael"},{"family":"Brand","given":"Randall"},{"family":"Chak","given":"Amitabh"},{"family":"Clain","given":"Jonathan"},{"family":"Cunningham","given":"John"},{"family":"Eloubeidi","given":"Mohamad"},{"family":"Gerdes","given":"Hans"},{"family":"Gress","given":"Frank"},{"family":"Jagannath","given":"Sanjay"},{"family":"Kantsevoy","given":"Sergey"},{"family":"LeBlanc","given":"Julia Kim"},{"family":"Levy","given":"Michael"},{"family":"Lightdale","given":"Charles"},{"family":"Romagnuolo","given":"Joseph"},{"family":"Saltzman","given":"John R."},{"family":"Savides","given":"Thomas"},{"family":"Wiersema","given":"Maurits"},{"family":"Woodward","given":"Timothy"},{"family":"Petersen","given":"Gloria"},{"family":"Canto","given":"Marcia"}],"issued":{"date-parts":[["2007",7]]}}},{"id":"BbVydael/MBLxDZhw","uris":[""],"uri":[""],"itemData":{"id":126,"type":"article-journal","title":"Endoscopic ultrasonography for surveillance of individuals at high risk for pancreatic cancer","container-title":"World Journal of Gastrointestinal Endoscopy","page":"272-285","volume":"6","issue":"7","source":"PubMed","abstract":"Pancreatic cancer is a highly lethal disease with a genetic susceptibility and familial aggregation found in 3%-16% of patients. Early diagnosis remains the only hope for curative treatment and improvement of prognosis. This can be reached by the implementation of an intensive screening program, actually recommended for individuals at high-risk for pancreatic cancer development. The aim of this strategy is to identify pre-malignant precursors or asymptomatic pancreatic cancer lesions, curable by surgery. Endoscopic ultrasound (EUS) with or without fine needle aspiration (FNA) seems to be the most promising technique for early detection of pancreatic cancer. It has been described as a highly sensitive and accurate tool, especially for small and cystic lesions. Pancreatic intraepithelial neoplasia, a precursor lesion which is highly represented in high-risk individuals, seems to have characteristics chronic pancreatitis-like changes well detected by EUS. Many screening protocols have demonstrated high diagnostic yields for pancreatic pre-malignant lesions, allowing prophylactic pancreatectomies. However, it shows a high interobserver variety even among experienced endosonographers and a low sensitivity in case of chronic pancreatitis. Some new techniques such as contrast-enhanced harmonic EUS, computer-aided diagnostic techniques, confocal laser endomicroscopy miniprobe and the detection of DNA abnormalities or protein markers by FNA, promise improvement of the diagnostic yield of EUS. As the resolution of imaging improves and as our knowledge of precursor lesions grows, we believe that EUS could become the most suitable method to detect curable pancreatic neoplasms in correctly identified asymptomatic at-risk patients.","DOI":"10.4253/wjge.v6.i7.272","ISSN":"1948-5190","note":"PMID: 25031786\nPMCID: PMC4094985","journalAbbreviation":"World J Gastrointest Endosc","language":"eng","author":[{"family":"Lami","given":"Gabriele"},{"family":"Biagini","given":"Maria Rosa"},{"family":"Galli","given":"Andrea"}],"issued":{"date-parts":[["2014",7,16]]}}}],"schema":""} [28,60].Several studies have reported an increased risk of PC in patients with pancreatic cysts, whatever the aetiology ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"rsgGKc4P","properties":{"formattedCitation":"\\super [73\\uc0\\u8211{}75]\\nosupersub{}","plainCitation":"[73–75]","noteIndex":0},"citationItems":[{"id":"BbVydael/1l2sN0tX","uris":[""],"uri":[""],"itemData":{"id":356,"type":"article-journal","title":"Non-branched microcysts of the pancreas on MR imaging of patients with pancreatic tumors who had pancreatectomy may predict the presence of pancreatic intraepithelial neoplasia (PanIN): a preliminary study","container-title":"European Radiology","source":"PubMed","abstract":"PURPOSE: To evaluate whether pancreatic parenchymal abnormalities on magnetic resonance imaging (MRI) are associated with pancreatic intraepithelial neoplasia (PanIN) on histology.\nMATERIALS AND METHODS: Retrospective study approved by institutional review board. One hundred patients (48 men, 52 women; mean age, 53.2?±?16.29 [SD]) underwent MRI before pancreatectomy for pancreatic tumors analyzed by two independent observers blinded to histopathological results for the presence of non-communicating microcysts and pancreatic atrophy (global or focal) beside tumors. MRI findings were compared to histopathological findings of resected specimens. Interobserver agreement was calculated. The association between parenchymal abnormalities and presence of PanIN was assessed by uni- and multivariate analyses.\nRESULTS: PanIN was present in 65/100 patients (65%). The presence of microcysts on MRI had a sensitivity of 52.3% (34/65 [95%CI, 51.92-52.70%]), a specificity of 77.1% (27/35 [95%CI, 76.70-77.59]), and accuracy of 61% (61/100 95%CI [50.7-70.6]) for the diagnosis of PanIN while global atrophy had a sensitivity of 24.6% (16/6 [95%CI, 24.28-24.95]) and a specificity of 97.1% (34/35 [95%CI, 96.97-97.32%]). In multivariate analysis, the presence of microcysts (OR, 3.37 [95%CI, 1.3-8.76]) (p?=?0.0127) and global atrophy (OR, 9.79 [95%CI, 1.21-79.129]) (p?=?0.0324) were identified as independent predictors of the presence of PanIN. The combination of these two findings was observed in 10/65 PanIN patients and not in patients without PanIN (p?=?0.013 with an OR of infinity [95%CI, 1.3-infinity]) and was not discriminant for PanIN-3 and lower grade (p?=?0.22). Interobserver agreement for the presence of microcysts was excellent (kappa?=?0.92), and for the presence of global atrophy, it was good (kappa?=?0.73).\nCONCLUSION: The presence of non-communicating microcysts on pre-operative MRI can be a significant predictor of PanIN in patients with pancreatic tumors.\nKEY POINTS: ? In patients with pancreatic tumors who had partial pancreatectomy, MR non-communicating pancreatic microcysts have a 52.3% sensitivity, a 77.1% specificity, and a 61% accuracy for the presence of PanIN with univariate and with an odds ratio of 3.37 with multivariate analyses. ? The association of global atrophy and non-communicating microcysts increases the predictive risk of PanIN.","DOI":"10.1007/s00330-019-06154-3","ISSN":"1432-1084","note":"PMID: 30972547","title-short":"Non-branched microcysts of the pancreas on MR imaging of patients with pancreatic tumors who had pancreatectomy may predict the presence of pancreatic intraepithelial neoplasia (PanIN)","journalAbbreviation":"Eur Radiol","language":"eng","author":[{"family":"Vullierme","given":"Marie-Pierre"},{"family":"Menassa","given":"Lina"},{"family":"Couvelard","given":"Anne"},{"family":"Rebours","given":"Vinciane"},{"family":"Maire","given":"Frédérique"},{"family":"Ibrahim","given":"Tony"},{"family":"Cros","given":"Jerome"},{"family":"Ruszniewski","given":"Philippe"},{"family":"Sauvanet","given":"Alain"},{"family":"Levy","given":"Philippe"},{"family":"Soyer","given":"Philippe"},{"family":"Vilgrain","given":"Valerie"}],"issued":{"date-parts":[["2019",4,10]]}}},{"id":"BbVydael/GFZYk5WI","uris":[""],"uri":[""],"itemData":{"id":360,"type":"article-journal","title":"Can endoscopic ultrasound predict pancreatic intraepithelial neoplasia lesions in chronic pancreatitis?: a retrospective study of pathologic correlation","container-title":"Pancreas","page":"849-854","volume":"43","issue":"6","source":"PubMed","abstract":"OBJECTIVE: This study aimed to evaluate associations between endoscopic ultrasound (EUS) criteria for chronic pancreatitis (CP) and coexisting pancreatic intraepithelial neoplasia (PanIN) lesions.\nMETHODS: Patients with known or suspected CP who underwent pancreatic resection within a year of EUS were selected. Histology slides and EUS images were reviewed for evidence of pancreatic fibrosis.\nRESULTS: Ninety-seven (51 men; mean age, 53 [12] years) underwent EUS within a 1 year or less of EUS. Pancreatic intraepithelial neoplasia lesions were found in 84 (87%) patients. Pancreatic intraepithelial neoplasia 1, 2, and 3 lesions were seen in 71 (83%), 10 (14%), and 1 (2%), respectively. Two patients had more than 1 PanIN grade (one had PanIN 1 and 2 and the other had PanIN 1 and 3). The mean number of EUS criteria for PanIN 1, 2, and 3 lesions were 3.9, 4.5, and 5.5, respectively. The odds ratio for the association between PanIN 2 and hyperechoic foci without shadowing in the pancreas head was 8.5 (P = 0.05). The odds ratio for the association between PanIN 2 and lobularity with honeycombing was 2.7 (P = ns). Advanced PanIN lesions had greater than or equal to 4 EUS criteria for CP.\nCONCLUSIONS: Pancreatic intraepithelial neoplasia lesions were highly prevalent in CP resections. Increasing PanIN grade is observed with increasing fibrosis score and increasing number of EUS criteria for CP.","DOI":"10.1097/MPA.0000000000000142","ISSN":"1536-4828","note":"PMID: 24826885","title-short":"Can endoscopic ultrasound predict pancreatic intraepithelial neoplasia lesions in chronic pancreatitis?","journalAbbreviation":"Pancreas","language":"eng","author":[{"family":"LeBlanc","given":"Julia Kim"},{"family":"Chen","given":"Jey-Hsin"},{"family":"Al-Haddad","given":"Mohammad"},{"family":"Luz","given":"Leticia"},{"family":"McHenry","given":"Lee"},{"family":"Sherman","given":"Stuart"},{"family":"Juan","given":"Michelle"},{"family":"Dewitt","given":"John"}],"issued":{"date-parts":[["2014",8]]}}},{"id":"BbVydael/cSZhI5Q3","uris":[""],"uri":[""],"itemData":{"id":362,"type":"article-journal","title":"Risk of pancreatic cancer in patients with pancreatic cyst","container-title":"Gastrointestinal Endoscopy","page":"81-86","volume":"84","issue":"1","source":"PubMed","abstract":"BACKGROUND AND AIMS: Certain pancreatic cysts (mucinous cystic neoplasm and side branch intraductal papillary mucinous neoplasm [IPMN]) have malignant potential and require surveillance. However, whether patients with pancreatic cysts have a higher long-term risk of pancreatic cancer (PaCa) has still not been established.\nMETHODS: This was a retrospective study of Veterans Administration patients. Patients noted to have pancreatic cysts on CT/magnetic resonance imaging (n?= 1050) were identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes. Patients aged?<15 years (n?= 425), patients with?<1 year of follow-up (n?=?13,259), and patients diagnosed to have PaCa within 1 year of identification of a pancreatic cyst (n?=?102) or within 1 year of follow-up in the remaining patients in the database (n?= 200) were excluded. Patients with pancreatic cystic lesions (group A, n?= 755) and the remaining patients in the database without cysts (group B, n?= 520,215) were followed from 1998 to?2007.\nRESULTS: During the study period, in group A and B PaCa was diagnosed in 17 and 1206 patients, respectively, and the incidence rate of PaCa was 5.08 and .32 per 1000 patient-years, respectively. The hazard ratio of PaCa in all patients with cysts was 19.64 (95% CI, 12.12-31.82; P?< .0001) when compared with the rest of the patients without cysts. In the subset of patients with cysts, without a history of acute or chronic pancreatitis (n?=?241), the hazard ratio of PaCa (n?= 5) was 18.80 (95% CI, 7.80-45.31; P?< .0001).\nCONCLUSION: Patients with pancreatic cysts have a significantly higher overall risk of PaCa. The etiologic distribution of cysts in our study patients is not available. Patients with mucinous cystic neoplasm and side branch IPMN are likely to have a higher risk of PaCa than our estimation of risk based on all etiologies.","DOI":"10.1016/j.gie.2015.10.030","ISSN":"1097-6779","note":"PMID: 26524643","journalAbbreviation":"Gastrointest. Endosc.","language":"eng","author":[{"family":"Munigala","given":"Satish"},{"family":"Gelrud","given":"Andres"},{"family":"Agarwal","given":"Banke"}],"issued":{"date-parts":[["2016",7]]}}}],"schema":""} [73–75]. In some cases, and especially in HRI, MRI with MRCP and diffusion-weighted MR sequences can help identify very small cysts that do not communicate with the pancreatic ducts ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"mp25RMc4","properties":{"formattedCitation":"\\super [73,74]\\nosupersub{}","plainCitation":"[73,74]","noteIndex":0},"citationItems":[{"id":"BbVydael/1l2sN0tX","uris":[""],"uri":[""],"itemData":{"id":356,"type":"article-journal","title":"Non-branched microcysts of the pancreas on MR imaging of patients with pancreatic tumors who had pancreatectomy may predict the presence of pancreatic intraepithelial neoplasia (PanIN): a preliminary study","container-title":"European Radiology","source":"PubMed","abstract":"PURPOSE: To evaluate whether pancreatic parenchymal abnormalities on magnetic resonance imaging (MRI) are associated with pancreatic intraepithelial neoplasia (PanIN) on histology.\nMATERIALS AND METHODS: Retrospective study approved by institutional review board. One hundred patients (48 men, 52 women; mean age, 53.2?±?16.29 [SD]) underwent MRI before pancreatectomy for pancreatic tumors analyzed by two independent observers blinded to histopathological results for the presence of non-communicating microcysts and pancreatic atrophy (global or focal) beside tumors. MRI findings were compared to histopathological findings of resected specimens. Interobserver agreement was calculated. The association between parenchymal abnormalities and presence of PanIN was assessed by uni- and multivariate analyses.\nRESULTS: PanIN was present in 65/100 patients (65%). The presence of microcysts on MRI had a sensitivity of 52.3% (34/65 [95%CI, 51.92-52.70%]), a specificity of 77.1% (27/35 [95%CI, 76.70-77.59]), and accuracy of 61% (61/100 95%CI [50.7-70.6]) for the diagnosis of PanIN while global atrophy had a sensitivity of 24.6% (16/6 [95%CI, 24.28-24.95]) and a specificity of 97.1% (34/35 [95%CI, 96.97-97.32%]). In multivariate analysis, the presence of microcysts (OR, 3.37 [95%CI, 1.3-8.76]) (p?=?0.0127) and global atrophy (OR, 9.79 [95%CI, 1.21-79.129]) (p?=?0.0324) were identified as independent predictors of the presence of PanIN. The combination of these two findings was observed in 10/65 PanIN patients and not in patients without PanIN (p?=?0.013 with an OR of infinity [95%CI, 1.3-infinity]) and was not discriminant for PanIN-3 and lower grade (p?=?0.22). Interobserver agreement for the presence of microcysts was excellent (kappa?=?0.92), and for the presence of global atrophy, it was good (kappa?=?0.73).\nCONCLUSION: The presence of non-communicating microcysts on pre-operative MRI can be a significant predictor of PanIN in patients with pancreatic tumors.\nKEY POINTS: ? In patients with pancreatic tumors who had partial pancreatectomy, MR non-communicating pancreatic microcysts have a 52.3% sensitivity, a 77.1% specificity, and a 61% accuracy for the presence of PanIN with univariate and with an odds ratio of 3.37 with multivariate analyses. ? The association of global atrophy and non-communicating microcysts increases the predictive risk of PanIN.","DOI":"10.1007/s00330-019-06154-3","ISSN":"1432-1084","note":"PMID: 30972547","title-short":"Non-branched microcysts of the pancreas on MR imaging of patients with pancreatic tumors who had pancreatectomy may predict the presence of pancreatic intraepithelial neoplasia (PanIN)","journalAbbreviation":"Eur Radiol","language":"eng","author":[{"family":"Vullierme","given":"Marie-Pierre"},{"family":"Menassa","given":"Lina"},{"family":"Couvelard","given":"Anne"},{"family":"Rebours","given":"Vinciane"},{"family":"Maire","given":"Frédérique"},{"family":"Ibrahim","given":"Tony"},{"family":"Cros","given":"Jerome"},{"family":"Ruszniewski","given":"Philippe"},{"family":"Sauvanet","given":"Alain"},{"family":"Levy","given":"Philippe"},{"family":"Soyer","given":"Philippe"},{"family":"Vilgrain","given":"Valerie"}],"issued":{"date-parts":[["2019",4,10]]}}},{"id":"BbVydael/GFZYk5WI","uris":[""],"uri":[""],"itemData":{"id":360,"type":"article-journal","title":"Can endoscopic ultrasound predict pancreatic intraepithelial neoplasia lesions in chronic pancreatitis?: a retrospective study of pathologic correlation","container-title":"Pancreas","page":"849-854","volume":"43","issue":"6","source":"PubMed","abstract":"OBJECTIVE: This study aimed to evaluate associations between endoscopic ultrasound (EUS) criteria for chronic pancreatitis (CP) and coexisting pancreatic intraepithelial neoplasia (PanIN) lesions.\nMETHODS: Patients with known or suspected CP who underwent pancreatic resection within a year of EUS were selected. Histology slides and EUS images were reviewed for evidence of pancreatic fibrosis.\nRESULTS: Ninety-seven (51 men; mean age, 53 [12] years) underwent EUS within a 1 year or less of EUS. Pancreatic intraepithelial neoplasia lesions were found in 84 (87%) patients. Pancreatic intraepithelial neoplasia 1, 2, and 3 lesions were seen in 71 (83%), 10 (14%), and 1 (2%), respectively. Two patients had more than 1 PanIN grade (one had PanIN 1 and 2 and the other had PanIN 1 and 3). The mean number of EUS criteria for PanIN 1, 2, and 3 lesions were 3.9, 4.5, and 5.5, respectively. The odds ratio for the association between PanIN 2 and hyperechoic foci without shadowing in the pancreas head was 8.5 (P = 0.05). The odds ratio for the association between PanIN 2 and lobularity with honeycombing was 2.7 (P = ns). Advanced PanIN lesions had greater than or equal to 4 EUS criteria for CP.\nCONCLUSIONS: Pancreatic intraepithelial neoplasia lesions were highly prevalent in CP resections. Increasing PanIN grade is observed with increasing fibrosis score and increasing number of EUS criteria for CP.","DOI":"10.1097/MPA.0000000000000142","ISSN":"1536-4828","note":"PMID: 24826885","title-short":"Can endoscopic ultrasound predict pancreatic intraepithelial neoplasia lesions in chronic pancreatitis?","journalAbbreviation":"Pancreas","language":"eng","author":[{"family":"LeBlanc","given":"Julia Kim"},{"family":"Chen","given":"Jey-Hsin"},{"family":"Al-Haddad","given":"Mohammad"},{"family":"Luz","given":"Leticia"},{"family":"McHenry","given":"Lee"},{"family":"Sherman","given":"Stuart"},{"family":"Juan","given":"Michelle"},{"family":"Dewitt","given":"John"}],"issued":{"date-parts":[["2014",8]]}}}],"schema":""} [73,74]. In a recent MRI study that included 100 patients, our group recently showed that the identification of non-communicating?pancreatic?microcysts?had a 52.3% sensitivity, a 77.1% specificity, and a 61% accuracy for the?diagnosis?of?PanIN ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"6U1Qf6Pq","properties":{"formattedCitation":"\\super [73]\\nosupersub{}","plainCitation":"[73]","noteIndex":0},"citationItems":[{"id":"BbVydael/1l2sN0tX","uris":[""],"uri":[""],"itemData":{"id":356,"type":"article-journal","title":"Non-branched microcysts of the pancreas on MR imaging of patients with pancreatic tumors who had pancreatectomy may predict the presence of pancreatic intraepithelial neoplasia (PanIN): a preliminary study","container-title":"European Radiology","source":"PubMed","abstract":"PURPOSE: To evaluate whether pancreatic parenchymal abnormalities on magnetic resonance imaging (MRI) are associated with pancreatic intraepithelial neoplasia (PanIN) on histology.\nMATERIALS AND METHODS: Retrospective study approved by institutional review board. One hundred patients (48 men, 52 women; mean age, 53.2?±?16.29 [SD]) underwent MRI before pancreatectomy for pancreatic tumors analyzed by two independent observers blinded to histopathological results for the presence of non-communicating microcysts and pancreatic atrophy (global or focal) beside tumors. MRI findings were compared to histopathological findings of resected specimens. Interobserver agreement was calculated. The association between parenchymal abnormalities and presence of PanIN was assessed by uni- and multivariate analyses.\nRESULTS: PanIN was present in 65/100 patients (65%). The presence of microcysts on MRI had a sensitivity of 52.3% (34/65 [95%CI, 51.92-52.70%]), a specificity of 77.1% (27/35 [95%CI, 76.70-77.59]), and accuracy of 61% (61/100 95%CI [50.7-70.6]) for the diagnosis of PanIN while global atrophy had a sensitivity of 24.6% (16/6 [95%CI, 24.28-24.95]) and a specificity of 97.1% (34/35 [95%CI, 96.97-97.32%]). In multivariate analysis, the presence of microcysts (OR, 3.37 [95%CI, 1.3-8.76]) (p?=?0.0127) and global atrophy (OR, 9.79 [95%CI, 1.21-79.129]) (p?=?0.0324) were identified as independent predictors of the presence of PanIN. The combination of these two findings was observed in 10/65 PanIN patients and not in patients without PanIN (p?=?0.013 with an OR of infinity [95%CI, 1.3-infinity]) and was not discriminant for PanIN-3 and lower grade (p?=?0.22). Interobserver agreement for the presence of microcysts was excellent (kappa?=?0.92), and for the presence of global atrophy, it was good (kappa?=?0.73).\nCONCLUSION: The presence of non-communicating microcysts on pre-operative MRI can be a significant predictor of PanIN in patients with pancreatic tumors.\nKEY POINTS: ? In patients with pancreatic tumors who had partial pancreatectomy, MR non-communicating pancreatic microcysts have a 52.3% sensitivity, a 77.1% specificity, and a 61% accuracy for the presence of PanIN with univariate and with an odds ratio of 3.37 with multivariate analyses. ? The association of global atrophy and non-communicating microcysts increases the predictive risk of PanIN.","DOI":"10.1007/s00330-019-06154-3","ISSN":"1432-1084","note":"PMID: 30972547","title-short":"Non-branched microcysts of the pancreas on MR imaging of patients with pancreatic tumors who had pancreatectomy may predict the presence of pancreatic intraepithelial neoplasia (PanIN)","journalAbbreviation":"Eur Radiol","language":"eng","author":[{"family":"Vullierme","given":"Marie-Pierre"},{"family":"Menassa","given":"Lina"},{"family":"Couvelard","given":"Anne"},{"family":"Rebours","given":"Vinciane"},{"family":"Maire","given":"Frédérique"},{"family":"Ibrahim","given":"Tony"},{"family":"Cros","given":"Jerome"},{"family":"Ruszniewski","given":"Philippe"},{"family":"Sauvanet","given":"Alain"},{"family":"Levy","given":"Philippe"},{"family":"Soyer","given":"Philippe"},{"family":"Vilgrain","given":"Valerie"}],"issued":{"date-parts":[["2019",4,10]]}}}],"schema":""} [73]. In the same study, the association of global atrophy and non-communicating?microcysts?increased the predictive risk of?PanIN.?Interobserver agreement for the?presence?of?microcysts?was excellent with MRI (kappa?=?0.92) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"HCaIUWiO","properties":{"formattedCitation":"\\super [73]\\nosupersub{}","plainCitation":"[73]","noteIndex":0},"citationItems":[{"id":"BbVydael/1l2sN0tX","uris":[""],"uri":[""],"itemData":{"id":356,"type":"article-journal","title":"Non-branched microcysts of the pancreas on MR imaging of patients with pancreatic tumors who had pancreatectomy may predict the presence of pancreatic intraepithelial neoplasia (PanIN): a preliminary study","container-title":"European Radiology","source":"PubMed","abstract":"PURPOSE: To evaluate whether pancreatic parenchymal abnormalities on magnetic resonance imaging (MRI) are associated with pancreatic intraepithelial neoplasia (PanIN) on histology.\nMATERIALS AND METHODS: Retrospective study approved by institutional review board. One hundred patients (48 men, 52 women; mean age, 53.2?±?16.29 [SD]) underwent MRI before pancreatectomy for pancreatic tumors analyzed by two independent observers blinded to histopathological results for the presence of non-communicating microcysts and pancreatic atrophy (global or focal) beside tumors. MRI findings were compared to histopathological findings of resected specimens. Interobserver agreement was calculated. The association between parenchymal abnormalities and presence of PanIN was assessed by uni- and multivariate analyses.\nRESULTS: PanIN was present in 65/100 patients (65%). The presence of microcysts on MRI had a sensitivity of 52.3% (34/65 [95%CI, 51.92-52.70%]), a specificity of 77.1% (27/35 [95%CI, 76.70-77.59]), and accuracy of 61% (61/100 95%CI [50.7-70.6]) for the diagnosis of PanIN while global atrophy had a sensitivity of 24.6% (16/6 [95%CI, 24.28-24.95]) and a specificity of 97.1% (34/35 [95%CI, 96.97-97.32%]). In multivariate analysis, the presence of microcysts (OR, 3.37 [95%CI, 1.3-8.76]) (p?=?0.0127) and global atrophy (OR, 9.79 [95%CI, 1.21-79.129]) (p?=?0.0324) were identified as independent predictors of the presence of PanIN. The combination of these two findings was observed in 10/65 PanIN patients and not in patients without PanIN (p?=?0.013 with an OR of infinity [95%CI, 1.3-infinity]) and was not discriminant for PanIN-3 and lower grade (p?=?0.22). Interobserver agreement for the presence of microcysts was excellent (kappa?=?0.92), and for the presence of global atrophy, it was good (kappa?=?0.73).\nCONCLUSION: The presence of non-communicating microcysts on pre-operative MRI can be a significant predictor of PanIN in patients with pancreatic tumors.\nKEY POINTS: ? In patients with pancreatic tumors who had partial pancreatectomy, MR non-communicating pancreatic microcysts have a 52.3% sensitivity, a 77.1% specificity, and a 61% accuracy for the presence of PanIN with univariate and with an odds ratio of 3.37 with multivariate analyses. ? The association of global atrophy and non-communicating microcysts increases the predictive risk of PanIN.","DOI":"10.1007/s00330-019-06154-3","ISSN":"1432-1084","note":"PMID: 30972547","title-short":"Non-branched microcysts of the pancreas on MR imaging of patients with pancreatic tumors who had pancreatectomy may predict the presence of pancreatic intraepithelial neoplasia (PanIN)","journalAbbreviation":"Eur Radiol","language":"eng","author":[{"family":"Vullierme","given":"Marie-Pierre"},{"family":"Menassa","given":"Lina"},{"family":"Couvelard","given":"Anne"},{"family":"Rebours","given":"Vinciane"},{"family":"Maire","given":"Frédérique"},{"family":"Ibrahim","given":"Tony"},{"family":"Cros","given":"Jerome"},{"family":"Ruszniewski","given":"Philippe"},{"family":"Sauvanet","given":"Alain"},{"family":"Levy","given":"Philippe"},{"family":"Soyer","given":"Philippe"},{"family":"Vilgrain","given":"Valerie"}],"issued":{"date-parts":[["2019",4,10]]}}}],"schema":""} [73]. Psychological impact of pancreatic screening The psychological burden in HRI of PC is significant because of the patient’s level of risk and his/her experience with close relatives suffering from this severe disease ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"hQq2wpHL","properties":{"formattedCitation":"\\super [15]\\nosupersub{}","plainCitation":"[15]","noteIndex":0},"citationItems":[{"id":"BbVydael/TT8LQAKI","uris":[""],"uri":[""],"itemData":{"id":79,"type":"article-journal","title":"Five years of prospective screening of high-risk individuals from families with familial pancreatic cancer","container-title":"Gut","page":"1410-1418","volume":"58","issue":"10","source":"PubMed","abstract":"OBJECTIVE: Familial pancreatic cancer (FPC) accounts for approximately 3% of all pancreatic cancer (PC) cases. It has been suggested that high-risk individuals (HRIs) should be offered a screening programme.\nAIM: To evaluate the diagnostic yield of a prospective screening programme in HRIs from families with FPC over a period of 5 years.\nMETHODS: HRIs of families with FPC of the National German Familial Pancreatic Cancer Registry (FaPaCa) were counselled and enrolled in a prospective, board-approved PC screening programme. Screening included clinical examination, laboratory tests, endoscopic ultrasound (EUS) and MRI with magnetic resonance cholangiopancreaticography (MRCP) and MR angiography.\nRESULTS: Between June 2002 and December 2007, 76 HRIs of families with FPC took part in the screening programme with a total of 182 examination visits. Twenty-eight patients revealed abnormalities in EUS (n = 25) and/or MR/MRCP (n = 12). In 7 patients fine needle aspiration cytology was performed. Operative pancreatic explorations were performed in 7 individuals, resulting in limited resections in 6 cases. Histopathological examination of the resected specimens showed serous oligocystic adenomas (n = 3), pancreatic intraepithelial neoplasia 1 (PanIN1) lesions with lobular fibrosis (n = 1), PanIN2 lesions (n = 1) and PanIN1 lesion plus a gastric type intraductal papillary mucinous neoplasm (IPMN) (n = 1).\nCONCLUSIONS: In FPC an EUS/MR/MRCP-based screening programme leads to the detection of potential precursor lesions of PC. However, the yield of an extensive screening programme is low, especially since the tumourigenic value of low grade PanIN lesions is not yet defined. Taking into account the enormous psychological stress for the tested individual and the high costs, a general PC screening in HRIs is not justified.","DOI":"10.1136/gut.2008.171611","ISSN":"1468-3288","note":"PMID: 19470496","journalAbbreviation":"Gut","language":"eng","author":[{"family":"Langer","given":"P."},{"family":"Kann","given":"P. H."},{"family":"Fendrich","given":"V."},{"family":"Habbe","given":"N."},{"family":"Schneider","given":"M."},{"family":"Sina","given":"M."},{"family":"Slater","given":"E. P."},{"family":"Heverhagen","given":"J. T."},{"family":"Gress","given":"T. M."},{"family":"Rothmund","given":"M."},{"family":"Bartsch","given":"D. K."}],"issued":{"date-parts":[["2009",10]]}}}],"schema":""} [15]. Patients must be informed that the aim of screening is to identify premalignant lesions or early invasive PC to propose a pancreatectomy with prophylactic and/or curative intent. Additionally, they must be informed of the potential benefits (avoiding the development of PC, being treated at a curable stage, or at least diagnosing PC at the earliest stage possible and prolonging survival) and risks (related to general anaesthesia and/or EUS and especially FNA, unnecessary pancreatic surgery with a risk of complications and diabetes) of pancreatic screening ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"mHh6BznD","properties":{"formattedCitation":"\\super [17]\\nosupersub{}","plainCitation":"[17]","noteIndex":0},"citationItems":[{"id":"BbVydael/Cz27nE6J","uris":[""],"uri":[""],"itemData":{"id":17,"type":"article-journal","title":"Evaluating Susceptibility to Pancreatic Cancer: ASCO Clinical Practice Provisional Clinical Opinion Summary","container-title":"Journal of Oncology Practice","page":"108-111","volume":"15","issue":"2","source":"PubMed","DOI":"10.1200/JOP.18.00629","ISSN":"1935-469X","note":"PMID: 30589608","title-short":"Evaluating Susceptibility to Pancreatic Cancer","journalAbbreviation":"J Oncol Pract","language":"eng","author":[{"family":"Stoffel","given":"Elena M."},{"family":"McKernin","given":"Shannon E."},{"family":"Khorana","given":"Alok A."}],"issued":{"date-parts":[["2019",2]]}}}],"schema":""} [17]. Moreover, because the sensitivity of the different imaging examinations is not 100%, patients must be informed of the risk of missing (pre)malignant lesions and developing advanced PC during follow-up intervals.Several studies have investigated the psychological burden of pancreatic screening and repeated examinations. Overall, pancreatic screening may have a positive psychological impact on HRI ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"zXHbrgNS","properties":{"formattedCitation":"\\super [76]\\nosupersub{}","plainCitation":"[76]","noteIndex":0},"citationItems":[{"id":"BbVydael/y5gLSIxH","uris":[""],"uri":[""],"itemData":{"id":86,"type":"article-journal","title":"Psychological impact of pancreatic cancer screening by EUS or magnetic resonance imaging in high-risk individuals: A systematic review","container-title":"Endoscopic Ultrasound","page":"17-24","volume":"8","issue":"1","source":"PubMed","abstract":"Background and Objectives: There is an increasing global interest in screening programs aiming to detect pancreatic cancer (PC) in an early and potentially curable stage. Concerns still remain as to whether screening would confer any survival benefit. Another approach to evaluate the benefits of the pancreatic screening programs would be to consider its impact on the quality of life of the individuals who at risk of developing cancer. The aim of this systematic review was to investigate the current knowledge regarding the psychological impact of participation in routine screening for PC.\nMethods: A systematic literature search was carried out in January 2018 in three major databases which are as follows: PubMed, Scopus, and Web of Science. Cross-sectional and prospective studies evaluating the psychological aspects of screening in high-risk individuals were included in the study. For each study, the following data were recorded: name of first author, year of publication, study design, study population, aims, screening protocol, outcomes and instruments, main results, and summary of findings.\nResults: Six cohort studies and one cross-sectional study that addressed the psychological aspects of PC screening were included in the analysis. Overall, studies have shown that high-risk individuals have positive psychological outcomes from participating in PC screening programs.\nConclusions: Although screening might not always be reassuring, it may improve individuals' quality of life, and this should be an important aspect when considering PC screening.","DOI":"10.4103/eus.eus_25_18","ISSN":"2303-9027","note":"PMID: 30246710","title-short":"Psychological impact of pancreatic cancer screening by EUS or magnetic resonance imaging in high-risk individuals","journalAbbreviation":"Endosc Ultrasound","language":"eng","author":[{"family":"Cazacu","given":"Irina Mihaela"},{"family":"Luzuriaga Chavez","given":"Adriana Alexandra"},{"family":"Saftoiu","given":"Adrian"},{"family":"Bhutani","given":"Manoop S."}],"issued":{"date-parts":[["2019",2]]}}}],"schema":""} [76]. Konings et al ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"qNV1DvAH","properties":{"formattedCitation":"\\super [48]\\nosupersub{}","plainCitation":"[48]","noteIndex":0},"citationItems":[{"id":"BbVydael/LgLhAzll","uris":[""],"uri":[""],"itemData":{"id":100,"type":"article-journal","title":"Evolution of features of chronic pancreatitis during endoscopic ultrasound-based surveillance of individuals at high risk for pancreatic cancer","container-title":"Endoscopy International Open","page":"E541-E548","volume":"6","issue":"5","source":"PubMed","abstract":"Background and study aims?: During endoscopic ultrasound (EUS)-based pancreatic ductal adenocarcinoma (PDAC)-surveillance in asymptomatic individuals, features of chronic pancreatitis (CP) are often detected. Little is known about the prevalence and progression of these features. The aim of this study was to quantify these features, assess the interobserver agreement, assess possible associated factors, and assess the natural course during 3 years of follow-up.\nPatients and methods?: Two experienced endosonographers reviewed anonymized sequential EUS videos of participants in PDAC surveillance that were obtained in 2012 and 2015 for features of CP. Descriptives, agreement analyses, univariate and multivariate analyses for possible risk factors, and repeated measures analyses to assess intra-individual changes over time were performed.\nResults?: A total of 42 EUS videos of 21 participants were reviewed. Any feature of CP was present in 86?% (2012) and 81?% (2015) of participants, with a mean of 2.5 features per individual. The overall interobserver agreement was almost perfect at 83?%. No baseline factors were significantly associated with features of CP. Features did not change over time, except for hyperechoic foci without shadowing, which decreased intra-individually (β?=?-?1.6, P ?=?0.005).\nConclusions?: This blinded study shows features of CP to be highly prevalent in individuals at high risk of developing pancreatic cancer. No baseline factors were associated with presence of these features. CP features did not increase intra-individually over a 3-year period. Longer follow-up and pathological examination of pancreatic resection specimens will be essential to learn whether EUS detection and follow-up of these CP features bear clinical relevance.","DOI":"10.1055/a-0574-2396","ISSN":"2364-3722","note":"PMID: 29713680\nPMCID: PMC5909773","journalAbbreviation":"Endosc Int Open","language":"eng","author":[{"family":"Konings","given":"Ingrid C. A. W."},{"family":"Cahen","given":"Djuna L."},{"family":"Harinck","given":"Femme"},{"family":"Fockens","given":"Paul"},{"family":"Hooft","given":"Jeanin E.","non-dropping-particle":"van"},{"family":"Poley","given":"Jan-Werner"},{"family":"Bruno","given":"Marco J."}],"issued":{"date-parts":[["2018",5]]}}}],"schema":""} [48] reported a low psychological burden due to the examinations themselves, which were considered uncomfortable only in 10% of cases. Of note, although it is an invasive procedure, EUS was generally not considered to be more uncomfortable than MRI ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"25zVMZYK","properties":{"formattedCitation":"\\super [48,76]\\nosupersub{}","plainCitation":"[48,76]","noteIndex":0},"citationItems":[{"id":"BbVydael/LgLhAzll","uris":[""],"uri":[""],"itemData":{"id":100,"type":"article-journal","title":"Evolution of features of chronic pancreatitis during endoscopic ultrasound-based surveillance of individuals at high risk for pancreatic cancer","container-title":"Endoscopy International Open","page":"E541-E548","volume":"6","issue":"5","source":"PubMed","abstract":"Background and study aims?: During endoscopic ultrasound (EUS)-based pancreatic ductal adenocarcinoma (PDAC)-surveillance in asymptomatic individuals, features of chronic pancreatitis (CP) are often detected. Little is known about the prevalence and progression of these features. The aim of this study was to quantify these features, assess the interobserver agreement, assess possible associated factors, and assess the natural course during 3 years of follow-up.\nPatients and methods?: Two experienced endosonographers reviewed anonymized sequential EUS videos of participants in PDAC surveillance that were obtained in 2012 and 2015 for features of CP. Descriptives, agreement analyses, univariate and multivariate analyses for possible risk factors, and repeated measures analyses to assess intra-individual changes over time were performed.\nResults?: A total of 42 EUS videos of 21 participants were reviewed. Any feature of CP was present in 86?% (2012) and 81?% (2015) of participants, with a mean of 2.5 features per individual. The overall interobserver agreement was almost perfect at 83?%. No baseline factors were significantly associated with features of CP. Features did not change over time, except for hyperechoic foci without shadowing, which decreased intra-individually (β?=?-?1.6, P ?=?0.005).\nConclusions?: This blinded study shows features of CP to be highly prevalent in individuals at high risk of developing pancreatic cancer. No baseline factors were associated with presence of these features. CP features did not increase intra-individually over a 3-year period. Longer follow-up and pathological examination of pancreatic resection specimens will be essential to learn whether EUS detection and follow-up of these CP features bear clinical relevance.","DOI":"10.1055/a-0574-2396","ISSN":"2364-3722","note":"PMID: 29713680\nPMCID: PMC5909773","journalAbbreviation":"Endosc Int Open","language":"eng","author":[{"family":"Konings","given":"Ingrid C. A. W."},{"family":"Cahen","given":"Djuna L."},{"family":"Harinck","given":"Femme"},{"family":"Fockens","given":"Paul"},{"family":"Hooft","given":"Jeanin E.","non-dropping-particle":"van"},{"family":"Poley","given":"Jan-Werner"},{"family":"Bruno","given":"Marco J."}],"issued":{"date-parts":[["2018",5]]}}},{"id":"BbVydael/y5gLSIxH","uris":[""],"uri":[""],"itemData":{"id":86,"type":"article-journal","title":"Psychological impact of pancreatic cancer screening by EUS or magnetic resonance imaging in high-risk individuals: A systematic review","container-title":"Endoscopic Ultrasound","page":"17-24","volume":"8","issue":"1","source":"PubMed","abstract":"Background and Objectives: There is an increasing global interest in screening programs aiming to detect pancreatic cancer (PC) in an early and potentially curable stage. Concerns still remain as to whether screening would confer any survival benefit. Another approach to evaluate the benefits of the pancreatic screening programs would be to consider its impact on the quality of life of the individuals who at risk of developing cancer. The aim of this systematic review was to investigate the current knowledge regarding the psychological impact of participation in routine screening for PC.\nMethods: A systematic literature search was carried out in January 2018 in three major databases which are as follows: PubMed, Scopus, and Web of Science. Cross-sectional and prospective studies evaluating the psychological aspects of screening in high-risk individuals were included in the study. For each study, the following data were recorded: name of first author, year of publication, study design, study population, aims, screening protocol, outcomes and instruments, main results, and summary of findings.\nResults: Six cohort studies and one cross-sectional study that addressed the psychological aspects of PC screening were included in the analysis. Overall, studies have shown that high-risk individuals have positive psychological outcomes from participating in PC screening programs.\nConclusions: Although screening might not always be reassuring, it may improve individuals' quality of life, and this should be an important aspect when considering PC screening.","DOI":"10.4103/eus.eus_25_18","ISSN":"2303-9027","note":"PMID: 30246710","title-short":"Psychological impact of pancreatic cancer screening by EUS or magnetic resonance imaging in high-risk individuals","journalAbbreviation":"Endosc Ultrasound","language":"eng","author":[{"family":"Cazacu","given":"Irina Mihaela"},{"family":"Luzuriaga Chavez","given":"Adriana Alexandra"},{"family":"Saftoiu","given":"Adrian"},{"family":"Bhutani","given":"Manoop S."}],"issued":{"date-parts":[["2019",2]]}}}],"schema":""} [48,76].Cost-effectiveness of pancreatic screening in high-risk individualsIt is difficult to assess the cost-effectiveness of pancreatic screening in HRI because of the different screening practices in different countries and the results of screening in different studies ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"rnkI1aG4","properties":{"formattedCitation":"\\super [10,11,17,18,23,24,40]\\nosupersub{}","plainCitation":"[10,11,17,18,23,24,40]","noteIndex":0},"citationItems":[{"id":"BbVydael/jiIYxhxp","uris":[""],"uri":[""],"itemData":{"id":65,"type":"article-journal","title":"PanGen-Fam: Spanish registry of hereditary pancreatic cancer","container-title":"European Journal of Cancer (Oxford, England: 1990)","page":"1911-1917","volume":"51","issue":"14","source":"PubMed","abstract":"PURPOSE: To describe the organisation of the registry and the preliminary results in terms of characteristics of high-risk pancreatic ductal adenocarcinoma (PDAC) families recruited to date and findings of the screening programme. To compare early onset sporadic cases (?50 years), sporadic cases (>50 years) and cases with family history of cancer, for PDAC possible risk factors.\nMETHODS/PATIENTS: Families with hereditary cancer syndromes predisposing to PDAC were recruited from two main sources: Spanish hospitals participating in PanGenEU, a pan-European multicentre case-control study, and their genetic counseling unit. Individuals at high-risk of PDAC were enrolled into a screening programme, consisting of Endoscopic ultrasound, computerised tomography, magnetic resonance imaging. Genetic testing of candidate genes was offered according to each patient's risk.\nRESULTS: Among 577 consecutive PDAC cases, recruited via PanGenEU, 36 (6%) had ?2 first-degree relative with PDAC: Familial pancreatic cancer (FPC). So far PanGen-Fam has recruited 42 high-risk PDAC families; 25 (60%) had FPC. Five index cases with cancer were positive for BRCA2 and one for BRCA1 germline mutations. In the second year of prospective PDAC screening, one neuroendocrine tumour and a high-grade dysplasia lesion suspicious of carcinoma were diagnosed among 41 high-risk individuals. Furthermore EUS detected chronic-pancreatitis-like parenchymal changes in 15 patients.\nCONCLUDING STATEMENT: The identification and recruitment of PDAC high-risk families into the PanGen-Fam registry provides an opportunity to detect early onset cancer and precursor pancreatic cancer lesions at a potentially curative stage and to increase the knowledge of the natural history of the disease.","DOI":"10.1016/j.ejca.2015.07.004","ISSN":"1879-0852","note":"PMID: 26212471","title-short":"PanGen-Fam","journalAbbreviation":"Eur. J. Cancer","language":"eng","author":[{"family":"Mocci","given":"E."},{"family":"Guillen-Ponce","given":"C."},{"family":"Earl","given":"J."},{"family":"Marquez","given":"M."},{"family":"Solera","given":"J."},{"family":"Salazar-López","given":"M.-T."},{"family":"Calcedo-Arnáiz","given":"C."},{"family":"Vázquez-Sequeiros","given":"E."},{"family":"Montans","given":"J."},{"family":"Mu?oz-Beltrán","given":"M."},{"family":"Vicente-Bártulos","given":"A."},{"family":"González-Gordaliza","given":"C."},{"family":"Sanjuanbenito","given":"A."},{"family":"Guerrero","given":"C."},{"family":"Mendía","given":"E."},{"family":"Lisa","given":"E."},{"family":"Lobo","given":"E."},{"family":"Martínez","given":"J. C."},{"family":"Real","given":"F. X."},{"family":"Malats","given":"N."},{"family":"Carrato","given":"A."}],"issued":{"date-parts":[["2015",9]]}}},{"id":"BbVydael/iMJ7y1A2","uris":[""],"uri":[""],"itemData":{"id":33,"type":"article-journal","title":"Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma: a patient-level meta-analysis and proposition of the Beaujon score","container-title":"United European Gastroenterology Journal","page":"205064061882491","source":"Crossref","DOI":"10.1177/2050640618824910","ISSN":"2050-6406, 2050-6414","title-short":"Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma","language":"en","author":[{"family":"Mestier","given":"Louis","non-dropping-particle":"de"},{"family":"Muller","given":"Marie"},{"family":"Cros","given":"Jér?me"},{"family":"Vullierme","given":"Marie-Pierre"},{"family":"Vernerey","given":"Dewi"},{"family":"Maire","given":"Frédérique"},{"family":"Dokmak","given":"Safi"},{"family":"Rebours","given":"Vinciane"},{"family":"Sauvanet","given":"Alain"},{"family":"Lévy","given":"Philippe"},{"family":"Hammel","given":"Pascal"}],"issued":{"date-parts":[["2019",1,12]]}}},{"id":"BbVydael/Cz27nE6J","uris":[""],"uri":[""],"itemData":{"id":17,"type":"article-journal","title":"Evaluating Susceptibility to Pancreatic Cancer: ASCO Clinical Practice Provisional Clinical Opinion Summary","container-title":"Journal of Oncology Practice","page":"108-111","volume":"15","issue":"2","source":"PubMed","DOI":"10.1200/JOP.18.00629","ISSN":"1935-469X","note":"PMID: 30589608","title-short":"Evaluating Susceptibility to Pancreatic Cancer","journalAbbreviation":"J Oncol Pract","language":"eng","author":[{"family":"Stoffel","given":"Elena M."},{"family":"McKernin","given":"Shannon E."},{"family":"Khorana","given":"Alok A."}],"issued":{"date-parts":[["2019",2]]}}},{"id":"BbVydael/C3zHNTfr","uris":[""],"uri":[""],"itemData":{"id":95,"type":"article-journal","title":"Results of surveillance in individuals at high-risk of pancreatic cancer: A systematic review and meta-analysis","container-title":"United European Gastroenterology Journal","page":"489-499","volume":"6","issue":"4","source":"PubMed","abstract":"Background: Data on surveillance for pancreatic ductal adenocarcinoma (PDAC) in high-risk individuals (HRIs) with \"familial pancreatic cancer\" (FPC) and specific syndromes are limited and heterogeneous.\nObjective: We conducted a systematic review and meta-analysis of PDAC surveillance studies in HRIs.\nMethods: Prevalence of solid/cystic pancreatic lesions and of lesions considered a successful target of surveillance (proven resectable PDAC and high-grade precursors) was pooled across studies. The rate of lesions diagnosed by endoscopic ultrasonography (EUS)/magnetic resonance imaging (MRI) and across different HRI groups was calculated.\nResults: Sixteen studies incorporating 1588 HRIs were included. The pooled prevalence of pancreatic solid and cystic lesions was 5.8% and 20.2%, respectively. The pooled prevalence of patients with lesions considered a successful target of surveillance was 3.3%, being similar to EUS or MRI and varying across subgroups, being 3% in FPC, 4% in hereditary pancreatitis, 5% in familial melanoma, 6.3% in hereditary breast/ovarian cancer, and 12.2% in Peutz-Jeghers syndrome. The pooled estimated rate of lesions considered a successful target of surveillance during follow-up was 5/1000 person-years.\nConclusion: Surveillance programs identify successful target lesions in 3.3% of HRIs with a similar yield of EUS and MRI and an annual risk of 0.5%. A higher rate of target lesions was reported in HRIs with specific DNA mutations.","DOI":"10.1177/2050640617752182","ISSN":"2050-6406","note":"PMID: 29881603\nPMCID: PMC5987280","title-short":"Results of surveillance in individuals at high-risk of pancreatic cancer","journalAbbreviation":"United European Gastroenterol J","language":"eng","author":[{"family":"Signoretti","given":"Marianna"},{"family":"Bruno","given":"Marco J."},{"family":"Zerboni","given":"Giulia"},{"family":"Poley","given":"Jan-Werner"},{"family":"Delle Fave","given":"Gianfranco"},{"family":"Capurso","given":"Gabriele"}],"issued":{"date-parts":[["2018",5]]}}},{"id":"BbVydael/7YSmGfQJ","uris":[""],"uri":[""],"itemData":{"id":134,"type":"article-journal","title":"Role of EUS in the early detection of small pancreatic cancer","container-title":"Digestive Endoscopy: Official Journal of the Japan Gastroenterological Endoscopy Society","page":"22-25","volume":"23 Suppl 1","source":"PubMed","abstract":"The prognosis of pancreatic cancer is extremely poor as a result of the difficulty in early detection of small pancreatic cancer and the intractable nature of appropriate anti-cancer therapies. Computed tomography (CT) is generally used for initial screening, but imaging sensitivities are generally insufficient to detect small masses. Endoscopic ultrasonography (EUS), in contrast, exhibits higher sensitivity than other imaging modalities for the detection of pancreatic cancers, because of the high resolution of images.\nAIMS: The goal of this study was to evaluate the role of EUS in the early detection of small pancreatic cancer.\nMETHODS: We retrospectively reviewed the Gifu University Hospital EUS database (November 2007 to October 2010), and extracted the data of patients whose aim was to confirm the presence or absence of pancreatic cancer subsequent to no tumor detection by abdominal CT.\nRESULTS: In a 3 year period, 132 patients underwent EUS to confirm the presence or absence of small pancreatic cancer. All patients had previously tested negative for pancreatic mass using abdominal CT, but had showed pancreatic cancer risk factors, including increased serum carcinoembryonic antigen and/or CA 19-9 (n = 106), serum amylase (n = 38), and/or mild to moderate dilation of the main pancreatic duct as determined by imaging (n = 88). EUS detected pancreatic mass in three of these patients. The masses in all three patients were minute (≤10 mm) and their presence was correlated with the detection of mild dilation of the main pancreatic duct in earlier CT scans. Increase of tumor markers was observed in two patients and hyperamylasemia and aggravation of diabetes were observed in one patient.\nCONCLUSIONS: EUS is strongly recommended for early detection of small pancreatic cancer in patients in whom the dilation of the main pancreatic duct was detected in previous imaging tests, with or without increase of pancreatic enzymes or tumor markers.","DOI":"10.1111/j.1443-1661.2011.01113.x","ISSN":"1443-1661","note":"PMID: 21535195","journalAbbreviation":"Dig Endosc","language":"eng","author":[{"family":"Yasuda","given":"Ichiro"},{"family":"Iwashita","given":"Takuji"},{"family":"Doi","given":"Shinpei"},{"family":"Nakashima","given":"Masanori"},{"family":"Moriwaki","given":"Hisataka"}],"issued":{"date-parts":[["2011",5]]}}},{"id":"BbVydael/NFPiCpG1","uris":[""],"uri":[""],"itemData":{"id":46,"type":"article-journal","title":"Screening for early pancreatic neoplasia in high-risk individuals: a prospective controlled study","container-title":"Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association","page":"766-781; quiz 665","volume":"4","issue":"6","source":"PubMed","abstract":"BACKGROUND & AIMS: Individuals with a strong family history of pancreatic cancer and persons with Peutz-Jeghers syndrome (PJS) have an increased risk for pancreatic cancer. This study screened for early pancreatic neoplasia and compared the pancreatic abnormalities in high-risk individuals and control subjects.\nMETHODS: High-risk individuals with PJS or a strong family history of pancreatic cancer were prospectively evaluated with baseline and 12-month computed tomography (CT) scan and endoscopic ultrasonography (EUS). If EUS was abnormal, EUS-fine-needle aspiration and endoscopic retrograde cholangiopancreatography (ERCP) were performed. Surgery was offered to patients with potentially neoplastic lesions. Radiologic findings and pathologic diagnoses were compared. Patients undergoing EUS and/or ERCP for benign non-pancreatic indications were concurrently enrolled as control subjects.\nRESULTS: Seventy-eight high-risk patients (72 from familial pancreatic cancer kindreds, 6 PJS) and 149 control patients were studied. To date, 8 patients with pancreatic neoplasia have been confirmed by surgery or fine-needle aspiration (10% yield of screening); 6 patients had 8 benign intraductal papillary mucinous neoplasms (IPMNs), 1 had an IPMN that progressed to invasive ductal adenocarcinoma, and 1 had pancreatic intraepithelial neoplasia. EUS and CT also diagnosed 3 patients with 5 extrapancreatic neoplasms. At EUS and ERCP abnormalities suggestive of chronic pancreatitis were more common in high-risk patients than in control subjects.\nCONCLUSIONS: Screening EUS and CT diagnosed significant asymptomatic pancreatic and extrapancreatic neoplasms in high-risk individuals. IPMN should be considered a part of the phenotype of familial pancreatic cancer. Abnormalities suggestive of chronic pancreatitis are identified more commonly at EUS and ERCP in high-risk individuals.","DOI":"10.1016/j.cgh.2006.02.005","ISSN":"1542-3565","note":"PMID: 16682259","title-short":"Screening for early pancreatic neoplasia in high-risk individuals","journalAbbreviation":"Clin. Gastroenterol. Hepatol.","language":"eng","author":[{"family":"Canto","given":"Marcia Irene"},{"family":"Goggins","given":"Michael"},{"family":"Hruban","given":"Ralph H."},{"family":"Petersen","given":"Gloria M."},{"family":"Giardiello","given":"Francis M."},{"family":"Yeo","given":"Charles"},{"family":"Fishman","given":"Elliott K."},{"family":"Brune","given":"Kieran"},{"family":"Axilbund","given":"Jennifer"},{"family":"Griffin","given":"Constance"},{"family":"Ali","given":"Syed"},{"family":"Richman","given":"Jeffrey"},{"family":"Jagannath","given":"Sanjay"},{"family":"Kantsevoy","given":"Sergey V."},{"family":"Kalloo","given":"Anthony N."}],"issued":{"date-parts":[["2006",6]]}}},{"id":"BbVydael/Y03HYTFt","uris":[""],"uri":[""],"itemData":{"id":136,"type":"article-journal","title":"German national case collection for familial pancreatic cancer (FaPaCa): ten years experience","container-title":"Familial Cancer","page":"323-330","volume":"10","issue":"2","source":"PubMed","abstract":"Familial pancreatic cancer (FPC) is a rare hereditary tumor syndrome. The 10-years experience of the national case collection for familial pancreatic cancer of Germany (FaPaCa) is reported. Since 1999 FaPaCa has collected families with at least two first-degree relatives with confirmed pancreatic cancer (PC), who did not fulfill the criteria of other hereditary tumor syndromes. Histopathological verification of tumor diagnoses, and genetic counseling were prerequisites for enrollment of families in FaPaCa. 94 of 452 evaluated families fulfilled the criteria for partaking in FaPaCa. PC represented the sole tumor entity in 38 (40%) families. In 56 families additional tumor types occurred, including breast cancer (n?=?28), colon cancer (n?=?20) and lung cancer (n?=?11). In 70 (74%) families the pattern of inheritance was consistent with an autosomal dominant trait. Compared to the preceding generation, a younger age of onset was observed in the offspring of PC patients (median: 57 vs. 69?years), indicating anticipation. Mutation analyses of BRCA2, PALB2, CDKN2a, RNASEL, STK11, NOD2, CHEK2 and PALLD, revealed deleterious causative germline mutations of BRCA2 and PALB2 in 2 of 70 (3%) and 2 of 41 (4.9%) German FPC families, respectively. Prospective PC screening with EUS, MRI and MRCP detected precancerous lesions (IPMN, multifocal PanIN2/3) or carcinoma in 5.5% (4 of 72) to 12.5% (9 of 72) of individuals at risk, depending on histological verification. Appropriate inclusion of families at high risk for PC in registries, such as FaPaCa, provides a unique and excellent tool to gain clinical and genetic knowledge of FPC. Focused research projects can be conducted most efficiently, when data of different FPC registries are combined.","DOI":"10.1007/s10689-010-9414-x","ISSN":"1573-7292","note":"PMID: 21207249","title-short":"German national case collection for familial pancreatic cancer (FaPaCa)","journalAbbreviation":"Fam. Cancer","language":"eng","author":[{"family":"Schneider","given":"Ralph"},{"family":"Slater","given":"Emily P."},{"family":"Sina","given":"Mercede"},{"family":"Habbe","given":"Nils"},{"family":"Fendrich","given":"Volker"},{"family":"Matth?i","given":"Elvira"},{"family":"Langer","given":"Peter"},{"family":"Bartsch","given":"Detlef K."}],"issued":{"date-parts":[["2011",6]]}}}],"schema":""} [10,11,17,18,23,24,40]. A screening test can generally be considered acceptable if there is a positive benefit/cost ratio. Rulyak et al ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"yFs3uORM","properties":{"formattedCitation":"\\super [38]\\nosupersub{}","plainCitation":"[38]","noteIndex":0},"citationItems":[{"id":"BbVydael/A1bcnT9r","uris":[""],"uri":[""],"itemData":{"id":84,"type":"article-journal","title":"Cost-effectiveness of pancreatic cancer screening in familial pancreatic cancer kindreds","container-title":"Gastrointestinal Endoscopy","page":"23-29","volume":"57","issue":"1","source":"PubMed","abstract":"BACKGROUND: Endoscopic screening of families predisposed to pancreatic cancer is increasingly used, but the cost-effectiveness of screening is unknown.\nMETHODS: A decision analysis was used to compare one-time screening for pancreatic dysplasia with EUS to no screening in a hypothetical cohort of 100 members of familial pancreatic cancer kindreds. Abnormal EUS findings are confirmed with ERCP and patients with abnormal findings are candidates for total pancreatectomy. Lifetime medical care costs and life expectancy were modeled, and the main analysis was conducted from the third-party payer perspective. The base-case analysis assumed a 20% prevalence of pancreatic dysplasia and 90% sensitivity of EUS and ERCP.\nRESULTS: Endoscopic screening was cost-effective, with an incremental cost-effectiveness ratio of $16,885/life-year saved. Screening was more cost-effective as the probability of dysplasia increased and as the sensitivity of EUS and ERCP increased. Screening remained cost-effective if the prevalence of dysplasia was greater than 16% or if the sensitivity of EUS was greater than 84%. Procedure costs had a limited impact on cost-effectiveness.\nCONCLUSIONS: Endoscopic screening of carefully selected members of familial pancreatic cancer kindreds appears to increase patient life expectancy in a cost-effective manner. Screening should be performed in centers that have experience with endoscopic screening for pancreatic dysplasia. The cost-effectiveness of repeated screening remains to be determined.","DOI":"10.1067/mge.2003.28","ISSN":"0016-5107","note":"PMID: 12518126","journalAbbreviation":"Gastrointest. Endosc.","language":"eng","author":[{"family":"Rulyak","given":"Stephen J."},{"family":"Kimmey","given":"Michael B."},{"family":"Veenstra","given":"David L."},{"family":"Brentnall","given":"Teresa A."}],"issued":{"date-parts":[["2003",1]]}}}],"schema":""} [38] compared one-time EUS-based screening to no screening in a hypothetical cohort of 100 HRI. They showed that screening increased life expectancy (38 years) in a cost-effective manner ($ 16885 per life-year saved). Latchford et al ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"YRml8L3R","properties":{"formattedCitation":"\\super [77]\\nosupersub{}","plainCitation":"[77]","noteIndex":0},"citationItems":[{"id":"BbVydael/v1RGG6zI","uris":[""],"uri":[""],"itemData":{"id":182,"type":"article-journal","title":"Peutz-Jeghers syndrome and screening for pancreatic cancer","container-title":"The British Journal of Surgery","page":"1446-1455","volume":"93","issue":"12","source":"PubMed","abstract":"BACKGROUND: Cancer risk, including pancreatic, is high in those with Peutz-Jeghers syndrome (PJS). It has been suggested that such patients should undergo screening for pancreatic cancer.\nMETHODS: The risk of pancreatic cancer in PJS, pancreatic screening and potential screening strategies were reviewed. Cost-effectiveness was assessed according to American Gastroenterology Association guidelines and a risk stratification model proposed by the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer.\nRESULTS: The risk of pancreatic cancer is increased in PJS but screening would cost over US 35,000 dollars per life saved. Risk stratification reduces cost by 100,000 dollars and costs fall to 50,000 dollars per life saved if deaths from other forms of cancer are avoided.\nCONCLUSION: Screening should be performed only on a research basis to evaluate the benefit and cost-effectiveness in high-risk groups.","DOI":"10.1002/bjs.5609","ISSN":"0007-1323","note":"PMID: 17115408","journalAbbreviation":"Br J Surg","language":"eng","author":[{"family":"Latchford","given":"A."},{"family":"Greenhalf","given":"W."},{"family":"Vitone","given":"L. J."},{"family":"Neoptolemos","given":"J. P."},{"family":"Lancaster","given":"G. A."},{"family":"Phillips","given":"R. K. S."}],"issued":{"date-parts":[["2006",12]]}}}],"schema":""} [77] created a model that showed that seven PCs would theoretically be detected in 250 patients who would undergo yearly EUS between the age of 40 and 55 years old. The cost would be $ 164.285 dollars per PC detected and $ 372708 per life saved. Overall, it is not clear whether EUS-based screening can be considered cost-effective ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"P4a30PaH","properties":{"formattedCitation":"\\super [60]\\nosupersub{}","plainCitation":"[60]","noteIndex":0},"citationItems":[{"id":"BbVydael/MBLxDZhw","uris":[""],"uri":[""],"itemData":{"id":126,"type":"article-journal","title":"Endoscopic ultrasonography for surveillance of individuals at high risk for pancreatic cancer","container-title":"World Journal of Gastrointestinal Endoscopy","page":"272-285","volume":"6","issue":"7","source":"PubMed","abstract":"Pancreatic cancer is a highly lethal disease with a genetic susceptibility and familial aggregation found in 3%-16% of patients. Early diagnosis remains the only hope for curative treatment and improvement of prognosis. This can be reached by the implementation of an intensive screening program, actually recommended for individuals at high-risk for pancreatic cancer development. The aim of this strategy is to identify pre-malignant precursors or asymptomatic pancreatic cancer lesions, curable by surgery. Endoscopic ultrasound (EUS) with or without fine needle aspiration (FNA) seems to be the most promising technique for early detection of pancreatic cancer. It has been described as a highly sensitive and accurate tool, especially for small and cystic lesions. Pancreatic intraepithelial neoplasia, a precursor lesion which is highly represented in high-risk individuals, seems to have characteristics chronic pancreatitis-like changes well detected by EUS. Many screening protocols have demonstrated high diagnostic yields for pancreatic pre-malignant lesions, allowing prophylactic pancreatectomies. However, it shows a high interobserver variety even among experienced endosonographers and a low sensitivity in case of chronic pancreatitis. Some new techniques such as contrast-enhanced harmonic EUS, computer-aided diagnostic techniques, confocal laser endomicroscopy miniprobe and the detection of DNA abnormalities or protein markers by FNA, promise improvement of the diagnostic yield of EUS. As the resolution of imaging improves and as our knowledge of precursor lesions grows, we believe that EUS could become the most suitable method to detect curable pancreatic neoplasms in correctly identified asymptomatic at-risk patients.","DOI":"10.4253/wjge.v6.i7.272","ISSN":"1948-5190","note":"PMID: 25031786\nPMCID: PMC4094985","journalAbbreviation":"World J Gastrointest Endosc","language":"eng","author":[{"family":"Lami","given":"Gabriele"},{"family":"Biagini","given":"Maria Rosa"},{"family":"Galli","given":"Andrea"}],"issued":{"date-parts":[["2014",7,16]]}}}],"schema":""} [60].conclusionPC is inherited in 5%-10% of cases. HRI of PC can benefit from pancreatic screening mainly based on annual MRI and EUS. Successful screening targets are early invasive PC and IPMN or PanIN with HGD, which may be treated surgically with curative intent. These lesions are identified in 2% to 5% of all HRI undergoing screening. EUS appears to be the best examination to identify small solid lesions and is complementary to MRI, whose performance may be higher for identifying small cystic lesions. Pancreatic abnormalities found by EUS are cystic lesions (13%-49% of HRI), solid lesions (0%-46%) and chronic pancreatitis-like parenchymal changes (> 50%). Of note, the latter frequently correspond to PanIN lesions. Finally, CH-EUS, EUS-elastography and other new techniques (including needle-based confocal laser endomicroscopy miniprobe and the detection of DNA abnormalities or protein markers by FNA) are being developed, but further studies are needed to evaluate their role in the management of HRI. There is still limited evidence on the accuracy, acceptability and cost of screening as it is currently recommended. HRI undergoing screening should continue to be included in large cohorts, such as the CAPS consortium (), which is a major opportunity to improve PC screening. Areas of currently unmet needs within the scope of hereditary PC include the following: (1) to constitute large cohorts of HRI undergoing long-term prospective follow-up; (2) to study the correlation between the pancreatic abnormalities identified at imaging (MRI and EUS) and the lesions identified at the pathological examination of surgically resected specimens; (3) to develop specific EUS and MRI training modules to improve the recognition of pancreatic lesions in HRI and interobserver agreement; (4) to develop new techniques such as biomarkers or new nuclear imaging techniques; and (5) to study more comprehensively the consequences of screening in terms of cost-effectiveness, psychological burden, and long-term surgical consequences in operated HRI.REFERENCES1 Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. 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Screening and surveillance for hereditary pancreatic cancer. Gastrointest Endosc 2002; 56: S82-S86 [PMID: 12297755 DOI: 10.1016/s0016-5107(02)70092-8]P-Reviewer: Friedel D, Vagholkar KRS-Editor: Tang JZ L-Editor: A E-Editor: Zhang YLSpecialty type: Gastroenterology and hepatologyCountry of origin: FrancePeer-review report classificationGrade A (Excellent): 0Grade B (Very good): BGrade C (Good): CGrade D (Fair): 0Grade E (Poor): 0Figure 1 Pancreatic cystic lesion: Intraductal papillary mucinous neoplasm.Figure 2 Intraductal papillary mucinous neoplasm with mural nodule.Figure 3 Chronic-pancreatitis-like parenchymal changes.Figure 4 Small hypoechoic nodule.Figure 5 Contrast-enhanced harmonic in endoscopic ultrasound: Hypoechoic suspect nodule.Figure 6 Fine needle aspiration of a solid pancreatic lesion.Table 1 Risk of pancreatic cancer based on genetic mutationsCondition GeneRelative risk of PC compared to the general populationRisk of pancreatic cancer at 70 yr (%)% Among inherited cancersNo family history10.5-1?2 first degree relatives with PCUnknown5-75-1280-853 first degree relatives with PCUnknown3240Hereditary breast ovarian cancer syndromeBRCA12-43-41-5BRCA22-104-55-20Genetic pancreatitisPRSS150-8040-551-4FAMMMCDKN2A10-255-252-3Peutz-Jeghers syndromeSTK11100-13030-401-3Lynch syndromeMLH1, MSH2, MSH6, PMS24-83-51-3PC: pancreatic cancer; FAMMM: Familial atypical multiple mole melanoma.Table 2 Main characteristics of high-risk individuals for pancreatic cancer in the different studiesFirst author/yrSettingHigh risk conditionPatients includedModalities of screeningImaging resultsPatients operated onOperated lesions seen only by the EUSHistological features with cancer or HGDBrentnall et al[37]Prospective, monocentricFPC14EUSCPis: 10 (77%)Cystic lesio:??Solid lesio: 6 (46%)71NA7 dysplasiaRulyak et al[38]Prospective, monocentricFPC35EUS, ERCP12 lesions12?12 dysplasiaKimmey et al[78]Prospective, monocentricFPC46EUS, ERCPCPis: 24 (52%)Cystic lesion:??Solid lesion: 12 (26%)???Canto et al[12]Prospective, monocentricFPC, PJS,38EUS first, +/- ERCP, CT, FNACPis: 17 (45%)Cystic lesion:??Solid lesion: 12 (31%)72/7 (1 PC, 1 PanIN3)1 PC1 PanIN3Canto et al[23]Prospective, monocentricFPC, PJS,78EUS, CT +/- ERCP, FNACPis: 61 (78%)Cystic lesion:?9 (12%)Solid lesion: 8 (10%)73/7 (1 PanIN 3, 2 PanIN1-2)1 PC+IPMN1 PanIN31PanIN3+IPMNPoley et al[13]Prospective, multicentricFPC, PJS, FAMMM, FBOC, HP, LFS44EUSCPis: 3 (7%)Cystic lesion:?7 (16%)Solid lesion: 3 (7%)101NA3 PCLanger et al[15]Prospective, multicentricFPC, FAMMM76EUS + MRICPis: 17 (22%)Cystic lesion:?3 (4%)Solid lesion: 7 (9%)75/7 (9/21 non operated lesions seen only in EUS)0 PC or PanIN3 or IPMN with HGDVerna et al[33]Prospective, monocentricFPC, FBOC51EUS n = 31 or MRI n = 33 +/- ERCP, FNACPis: 9 (29%)Cystic lesion:?12 (39%)Solid lesion: 2 (6%)5?(2 solid lesions in EUS and MRI)1 PC1 PanIN2Ludwig et al[34]Prospective, monocentricFPC109MRCP or CT EUS, FNA18 lesions6?1 PC2 MD IPMN1 PanIN-31 PanIN-2Schneider et al[40]Prospective, monocentricFPC, FAMMM72EUS, MRI13 lesions9?1 PC1 PanIN-3Zubarik et al[16]Prospective, monocentricFPC, PJS, BRCA227CA19-9 +/- EUS (27/546)5 lesions51NA1 PCCanto et al[25]Prospective, multicentricFPC, FBOC, PJS216CT, EUS, MRI/MRCPCPis: 54 (25%)Cystic lesion:?79 (36%)Solid lesion: 3 (1.4%)5?(20/216 non operated lesions seen only in EUS including 3 solid lesion)2 MD-IPMN1 IPMN+PanIN3Al-Sukhni et al[32]Prospective, monocentricFPC, BRCA1/2, FAMMM, LKB1252MRI, +/- CT, EUS, ERCPCPis:??Cystic lesion:?80 (32%)Solid lesion: 3 (1.2%)43 PCSud et al[14]Prospective, monocentricFPC, BRCA1/2, MMR, CDKN2A, LKB1, PRSS130EUS +/- FNA3 lesions31NA2 PCMocci et al[10]Prospective, multicentricFPC, CDKN2A, MMR, PRSS141EUS, CT +/- MRI, FNACPis:?15 (37%)Cystic lesion:4 (10%)Solid lesion: 2 (5%)12NA1 NET1 PanIN3Vasen et al[31]Prospective, multicentricFPC, CDKN2A, BRCA 1/2411MRI, EUS, CT, FNACPis:??Cystic lesion: 138 (34%)Solid lesion: 16 (4%)302/30 (866 MRIs and 106 EUS performed)16 PC3 PanIN31 IPMN with high gradeBartsch et al[4]Prospective, multicentricFPC, BRCA1/2, PALB2234MRI, EUS, CT, FNACPis:??Cystic lesion: 125 (49%)Solid lesion: 9 (4%)216/253 (2%) lesions (2 malignant and HGD)?2 PC3 PanIN31 IPMN with HGD;multifocal PanIN2±BD-IPMN±AFL1 NET8 PanIN-2Harinck et al[27]Prospective, multicentricFPC, BRCA1/2, CDKN2A, LKB1, TP53, MMR139MRI +/- EUSCPis:?41 (30%)Cystic lesion: 67 (48%)Solid lesion: 2 (1.4%)22/2 (1 PC, 1 PanIN-2)1 PC1 PanIN-21NA: Not applicable, because patients had only endoscopic ultrasound (EUS); 2NA: Not applicable, because patients had an EUS only if magnetic resonance imaging was abnormal. Three patients developed pancreatic cancer during the screening. CPis: Chronic-pancreatitis-like parenchymal changes; CT: Computed tomography; EUS: Endoscopic ultrasound; FNA: Fine needle aspiration; FPC: Familial pancreatic cancer; IPMN: Intraductal papillary mucinous neoplasm; MRI: Magnetic resonance imaging; PanIN: Pancreatic intraneoplasia; PC: Pancreatic cancer; ERCP: Endoscopic retrograde cholangiopancreaticography; HGD: High-grade dysplasia. ................
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