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Name of Journal: World Journal of Clinical PediatricsESPS Manuscript NO: 30201Manuscript Type: Original ArticleObservational StudyDecision-making patterns in managing children with suspected biliary dyskinesia?Nakayuenyongsuk W et al. Managing children with functional gallbladder disorder?Warapan Nakayuenyongsuk, Hassan Choudry, Karla Au Yeung, Wikrom Karnsakul Warapan Nakayuenyongsuk, Lucile Packard Children's Hospital, Stanford University School of Medicine, Palo Alto, CA 94305, United States?Hassan Choudry, Karla Au Yeung, Wikrom Karnsakul, Pediatric Liver Center, Johns Hopkins University School of Medicine, Baltimore, Baltimore, MD 21287, United StatesInstitutional review board statement: The study was reviewed and approved by Institutional review board statement of Johns Hopkins University School of Medicine. Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.Data sharing statement: No additional data are available.Open-Access: This article is an open-access article which 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: source: Invited manuscriptCorrespondence to: Wikrom Karnsakul, MD, Associate Professor, Pediatric Liver Center, Johns Hopkins University School of Medicine, CMSC-2?600 North Wolfe Street, Baltimore, MD 21287, United States.?wkarnsa1@jhmi.edu?Telephone: +1-410-9558769?Fax: +1-410-9551464?Received: September 19, 2016Peer-review started: September 20, 2016First decision: October 28, 2016Revised: December 4, 2016Accepted: January 11, 2017Article in press:Published online:Abstract?AIMTo explore and to analyze the patterns in decision-making by pediatric gastroenterologists in managing a child with a suspected diagnosis of functional gallbladder disorder (FGBD).METHODSThe questionnaire survey included a case history with right upper quadrant pain and was sent to pediatric gastroenterologists worldwide via an internet list server called the PED GI Bulletin Board.RESULTSDifferences in decision-making among respondents in managing this case were observed at each level of investigations and management. Cholecystokinin-scintigraphy scan (CCK-CS) was the most common investigation followed by an endoscopy. A proton pump inhibitor was most commonly prescribed treating the condition. The majority of respondents considered a referral for a surgical evaluation when CCK-CS showed a decreased GBEF value with biliary-type pain during CCK injection.? CONCLUSIONCCK infusion rate in CCK-CS-CS and GBEF cut-off limits were inconsistent throughout practices. The criteria for a referral to a surgeon were not uniform from one practitioner to another. A multidisciplinary team approach with pediatric gastroenterologists and surgeons is required guide the decision-making managing a child with suspected FGBD. ?Key words:?Functional gallbladder disorder; Biliary dyskinesia; Cholecystectomy; Gallbladder ejection fraction? The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.Core tip: Functional gallbladder disorder (FGBD) is a common motility disorder of the gallbladder that results in abdominal pain and cholecystectomy in children. The guideline for managing children with FGBD is lacking. The questionnaire survey is a pilot study performed by pediatric gastroenterologists worldwide via the PED GI Bulletin Board. Differences in decision-making among respondents in managing this case were observed at each level of investigations and management. Since, a different risk-benefit ratio should be considered in children with suspected FGBD. The authors include an algorithm for the approach in managing children with suspected FGBD based on literature review.Nakayuenyongsuk W, Choudry H, Yeung KA, Karnsakul W. Decision-making Patterns in managing children with suspected biliary dyskinesia. World J Clin Pediatr 2017; In pressINTRODUCTION?Functional gallbladder disorder (FGBD) is a motility disorder of the gallbladder that results in decreased contractility of the gallbladder and colicky pain in the epigastrium and/or the right upper quadrant of the abdomen (RUQ). FGBD was previously called chronic acalculous cholecystitis, acalculous cholecystitis, or biliary dyskinesia and is a diagnosis of exclusion. Therefore further investigations are routinely performed to exclude other hepatobiliary or gastrointestinal diseases. Experts’ consensus developed the Rome III criteria in 2006 ADDIN EN.CITE <EndNote><Cite><Author>Behar</Author><Year>2006</Year><RecNum>1</RecNum><DisplayText>[1]</DisplayText><record><rec-number>1</rec-number><foreign-keys><key app="EN" db-id="t09ara25evxzp2etsasptapzar5w05wvszt0" timestamp="1467237802">1</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Behar, J.</author><author>Corazziari, E.</author><author>Guelrud, M.</author><author>Hogan, W.</author><author>Sherman, S.</author><author>Toouli, J.</author></authors></contributors><auth-address>Rhode Island Hospital and Brown University School of Medicine, Providence, Rhode Island 02903, USA. Jose_Behar@brown.edu</auth-address><titles><title>Functional gallbladder and sphincter of oddi disorders</title><secondary-title>Gastroenterology</secondary-title></titles><periodical><full-title>Gastroenterology</full-title></periodical><pages>1498-509</pages><volume>130</volume><number>5</number><keywords><keyword>Cholangiopancreatography, Endoscopic Retrograde</keyword><keyword>Common Bile Duct Diseases/*diagnosis/epidemiology/therapy</keyword><keyword>Gallbladder Diseases/*diagnosis/epidemiology</keyword><keyword>Humans</keyword><keyword>Manometry</keyword><keyword>*Sphincter of Oddi</keyword></keywords><dates><year>2006</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0016-5085 (Print)
0016-5085 (Linking)</isbn><accession-num>16678563</accession-num><urls><related-urls><url>;[1] to help guide the management of FGBD. A child who is suspected to have FGBD must experience recurrent episodes of the abdominal pain which last longer than 30 minutes without relief after bowel movements, postural changes or antacids. The child must have normal liver enzymes, conjugated bilirubin, and amylase/lipase. In addition, the gallbladder must be present and other structural diseases must be excluded. Supportive criteria include the presence of nausea and vomiting, classic biliary pain at RUQ that radiates to the back and/or right infra subscapular region, and pain disturbing sleep ADDIN EN.CITE <EndNote><Cite><Author>Behar</Author><Year>2006</Year><RecNum>1</RecNum><DisplayText>[1]</DisplayText><record><rec-number>1</rec-number><foreign-keys><key app="EN" db-id="t09ara25evxzp2etsasptapzar5w05wvszt0" timestamp="1467237802">1</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Behar, J.</author><author>Corazziari, E.</author><author>Guelrud, M.</author><author>Hogan, W.</author><author>Sherman, S.</author><author>Toouli, J.</author></authors></contributors><auth-address>Rhode Island Hospital and Brown University School of Medicine, Providence, Rhode Island 02903, USA. Jose_Behar@brown.edu</auth-address><titles><title>Functional gallbladder and sphincter of oddi disorders</title><secondary-title>Gastroenterology</secondary-title></titles><periodical><full-title>Gastroenterology</full-title></periodical><pages>1498-509</pages><volume>130</volume><number>5</number><keywords><keyword>Cholangiopancreatography, Endoscopic Retrograde</keyword><keyword>Common Bile Duct Diseases/*diagnosis/epidemiology/therapy</keyword><keyword>Gallbladder Diseases/*diagnosis/epidemiology</keyword><keyword>Humans</keyword><keyword>Manometry</keyword><keyword>*Sphincter of Oddi</keyword></keywords><dates><year>2006</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0016-5085 (Print)
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ADDIN EN.CITE.DATA [2-8]. The study involves a questionnaire based survey delivered to pediatric gastroenterologist members via the PED GI Bulletin Board, the internet list server. The objective of the study was to explore and to analyze the patterns in decision-making by pediatric gastroenterologists in managing a child with a suspected diagnosis of FGBD. ?MATERIALS AND METHODSThis is a questionnaire-based survey distributed to the PED GI Bulletin Board accessible by hundreds of pediatric gastroenterologists worldwide. The PEDGI Bulletin Board is the internet list server that encourages pediatric gastroenterologists and hepatologists worldwide to communicate with one another electronically. This study was approved by the Institutional Review Board of Johns Hopkins School of Medicine. At the beginning of the questionnaire introduced to the GI bulletin board, only practicing pediatric gastroenterologists (not trainees) were requested and consented themselves to perform the questionnaire. The survey data were collected from the participating PEDGI Bulletin Board users who used the network from January 2011 to April 2011. The survey was completed and analyzed using an Internet-based questionnaire (, Portland, Oregon, United States). The questionnaire was designed to have participants complete within 10 min. The survey includes a case history with right upper quadrant pain in Figure 1. The questionnaire consists of 7 questions (Q 1-7) in order to observe the patterns of decision-making in managing the case (Figure 1). Q 1 gives a direction at the initial step whether the patient should have a test or a medical or surgical treatment performed first. Q 2-3?is specifically addressed to the types and the duration of such medical treatments. Q 4 is related to the decision-making patterns?in investigations. Q 5-7 is for their criteria for the CCK-CS and GBEF cut-off limits in diagnosing FGBD and the surgical treatment of FGBD. RESULTS?The questionnaire survey consisted of 7 questions. One hundred pediatric gastroenterologists participated in the questionnaire study. Of these 100 respondents, 99 completed all questions in the survey, and 71 informed the location of their practices (60 in the US and 11 from non-US countries). For Q 1 and 2, 19 respondents (19%) decided to treat the abdominal pain with the medical treatment first. Of these 19 respondents, 13 (68.4%) selected proton pump inhibitors (PPI), 8 (42.1%) for antispasmodics, 1 (5.3%) for acetaminophen, 2 for histamine 2 receptor antagonists, 1 for probiotic, 1 for cyproheptadine as their choices of the treatment. In Q 3, 17 respondents answered the duration of such a medical treatment.?Interestingly, 2 respondents in Q1 referred the patient to a surgeon without further investigations or a treatment trial.Figure 2 demonstrated the patterns in decision-making of the ordered investigations (Q 4). CCK-CS?(67.7%) and an upper endoscopy (52.9%) were the most commonly ordered tests. Q 5-7 indicated the techniques used for CCK-CS and the criteria of GBEF cut-off limits used to diagnose FGBD and to refer to a surgeon for an evaluation for cholecystectomy at their institutions. Seventy-six respondents responded to Q 6 and different GBEF cutoff limits were used, < 35% in 43 respondents (56.6%), < 40% in 17 respondents (22.4%), < 30% in 3 respondents, < 25% in 3 respondents, < 20% in one respondent, and < 15% in one respondent (Table 1). Four respondents did not know the GBEF cutoff limits at their institutions. Three respondents decided not to order or to avoid ordering the test, and one respondent did not have the test available at the institution.?Sixty-three respondents responded to Q 6. While 49 respondents (77.8%) selected CCK-CS with the rapid infusion of CCK over 2-3 minutes as the technique used at their institutions, 14 (22.2%) chose the CCK-CS technique with the slow infusion over 30-60 minutes.?For Q 7, the majority of respondents (64%) responded by referring the patient to a surgeon with the criteria when both the GBEF value was abnormal and similar types of abdominal pain was reproduced during the infusion of CCK (Figure 3). DISCUSSION?Several GI diseases and biliary disorders share a similar type of abdominal pain. The presentation of this clinical vignette described in the questionnaire is consistent with FGBD defined by the ROME III criteria when all known causes of epigastric and/or RUQ pain are excluded ADDIN EN.CITE <EndNote><Cite><Author>Behar</Author><Year>2006</Year><RecNum>1</RecNum><DisplayText>[1]</DisplayText><record><rec-number>1</rec-number><foreign-keys><key app="EN" db-id="t09ara25evxzp2etsasptapzar5w05wvszt0" timestamp="1467237802">1</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Behar, J.</author><author>Corazziari, E.</author><author>Guelrud, M.</author><author>Hogan, W.</author><author>Sherman, S.</author><author>Toouli, J.</author></authors></contributors><auth-address>Rhode Island Hospital and Brown University School of Medicine, Providence, Rhode Island 02903, USA. Jose_Behar@brown.edu</auth-address><titles><title>Functional gallbladder and sphincter of oddi disorders</title><secondary-title>Gastroenterology</secondary-title></titles><periodical><full-title>Gastroenterology</full-title></periodical><pages>1498-509</pages><volume>130</volume><number>5</number><keywords><keyword>Cholangiopancreatography, Endoscopic Retrograde</keyword><keyword>Common Bile Duct Diseases/*diagnosis/epidemiology/therapy</keyword><keyword>Gallbladder Diseases/*diagnosis/epidemiology</keyword><keyword>Humans</keyword><keyword>Manometry</keyword><keyword>*Sphincter of Oddi</keyword></keywords><dates><year>2006</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0016-5085 (Print)
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ADDIN EN.CITE.DATA [1,9]. Few case reports described children with the diagnosis of FGBD who had a complete relief from the abdominal pain when a PPI was usedPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5LYXJuc2FrdWw8L0F1dGhvcj48WWVhcj4yMDExPC9ZZWFy
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ADDIN EN.CITE.DATA [12,13]. Since these tests were already ordered and reported as normal in the clinical vignette, CCK-CS and an upper endoscopy were observed to be the most common tests chosen by respondents. Biopsies of the proximal GI tract are generally considered even in the absence of gross endoscopic findings as microscopic endoscopic findings may reveal features of eosinophilic gastritis, GERD, Helicobacter pylori (H. pylori) infection, Crohn's disease, and villus atrophy in those who were also diagnosed with FGBDPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5LYXJuc2FrdWw8L0F1dGhvcj48WWVhcj4yMDExPC9ZZWFy
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ADDIN EN.CITE.DATA [10,14,15] to look for mucosal disease that might explain symptoms or improve symptoms when treated. For example, Tutel’ian et alPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5UdXRlbCZhcG9zO2lhbjwvQXV0aG9yPjxZZWFyPjIwMDM8
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ADDIN EN.CITE.DATA [16] reported chronic atrophic gastritis from H. pylori infection in patients who were diagnosed with FGBD prior to the endoscopy. A series of children with FGBD were later diagnosed with Crohn’s disease, hiatal hernia, and cyclic vomitingPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5UdXRlbCZhcG9zO2lhbjwvQXV0aG9yPjxZZWFyPjIwMDM8
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ADDIN EN.CITE.DATA [16], and with esophagitis, H. pylori infection and duodenitis after cholecystectomyPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TaW5naGFsPC9BdXRob3I+PFllYXI+MjAxMjwvWWVhcj48
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ADDIN EN.CITE.DATA [17]. Children with functional constipation had a significant impairment of the gallbladder motilityPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NZWhyYTwvQXV0aG9yPjxZZWFyPjIwMTU8L1llYXI+PFJl
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ADDIN EN.CITE.DATA [19,20]. According to the ROME III criteria a continuous intravenous CCK infusion over a 30-minute period is preferred ADDIN EN.CITE <EndNote><Cite><Author>Behar</Author><Year>2006</Year><RecNum>1</RecNum><DisplayText>[1]</DisplayText><record><rec-number>1</rec-number><foreign-keys><key app="EN" db-id="t09ara25evxzp2etsasptapzar5w05wvszt0" timestamp="1467237802">1</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Behar, J.</author><author>Corazziari, E.</author><author>Guelrud, M.</author><author>Hogan, W.</author><author>Sherman, S.</author><author>Toouli, J.</author></authors></contributors><auth-address>Rhode Island Hospital and Brown University School of Medicine, Providence, Rhode Island 02903, USA. Jose_Behar@brown.edu</auth-address><titles><title>Functional gallbladder and sphincter of oddi disorders</title><secondary-title>Gastroenterology</secondary-title></titles><periodical><full-title>Gastroenterology</full-title></periodical><pages>1498-509</pages><volume>130</volume><number>5</number><keywords><keyword>Cholangiopancreatography, Endoscopic Retrograde</keyword><keyword>Common Bile Duct Diseases/*diagnosis/epidemiology/therapy</keyword><keyword>Gallbladder Diseases/*diagnosis/epidemiology</keyword><keyword>Humans</keyword><keyword>Manometry</keyword><keyword>*Sphincter of Oddi</keyword></keywords><dates><year>2006</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0016-5085 (Print)
0016-5085 (Linking)</isbn><accession-num>16678563</accession-num><urls><related-urls><url>;[1]. On the contrary, the new guidelines from the Gastrointestinal Council of the Society of Nuclear Medicine recommend the slow infusion rate of the CCK over 60 min as the standard test in adults since this technique generates a physiologic response for contraction of the gallbladder and discourage the evidence of the reproducible pain after the CCK injection during CCK-CSPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5aaWVzc21hbjwvQXV0aG9yPjxZZWFyPjIwMDE8L1llYXI+
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ADDIN EN.CITE.DATA [19,21] .? Table 1 demonstrates the difference in the GBEF cut-off limits used as the criteria to guide the management for the questionnaire respondents (Table 1). The GBEF cut-off limits vary from 15%-40% in the reported literature depending on the CCK-CS techniques ADDIN EN.CITE <EndNote><Cite><Author>Telega</Author><Year>2006</Year><RecNum>25</RecNum><DisplayText>[22]</DisplayText><record><rec-number>25</rec-number><foreign-keys><key app="EN" db-id="t09ara25evxzp2etsasptapzar5w05wvszt0" timestamp="1467241448">25</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Telega, G.</author></authors></contributors><auth-address>Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226-0509, USA. telega@mcw.edu</auth-address><titles><title>Biliary dyskinesia in pediatrics</title><secondary-title>Curr Gastroenterol Rep</secondary-title></titles><periodical><full-title>Curr Gastroenterol Rep</full-title></periodical><pages>172-6</pages><volume>8</volume><number>2</number><keywords><keyword>Abdominal Pain/etiology</keyword><keyword>Biliary Dyskinesia/*diagnosis/etiology/therapy</keyword><keyword>Case-Control Studies</keyword><keyword>Child</keyword><keyword>Humans</keyword><keyword>Retrospective Studies</keyword><keyword>Treatment Outcome</keyword></keywords><dates><year>2006</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>1522-8037 (Print)
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ADDIN EN.CITE.DATA [8]. A CCK provocation test is even a better predictor for the resolution of symptoms than using GBEF cut-off limits alone after cholecystectomy ADDIN EN.CITE <EndNote><Cite><Author>Morris-Stiff</Author><Year>2011</Year><RecNum>27</RecNum><DisplayText>[24]</DisplayText><record><rec-number>27</rec-number><foreign-keys><key app="EN" db-id="t09ara25evxzp2etsasptapzar5w05wvszt0" timestamp="1467241576">27</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Morris-Stiff, G.</author><author>Falk, G.</author><author>Kraynak, L.</author><author>Rosenblatt, S.</author></authors></contributors><auth-address>Department of General Surgery, Cleveland Clinic Foundation, Cleveland, OH, USA.</auth-address><titles><title>The cholecystokin provocation HIDA test: recreation of symptoms is superior to ejection fraction in predicting medium-term outcomes</title><secondary-title>J Gastrointest Surg</secondary-title></titles><periodical><full-title>J Gastrointest Surg</full-title></periodical><pages>345-9</pages><volume>15</volume><number>2</number><keywords><keyword>Adult</keyword><keyword>Biliary Dyskinesia/physiopathology/*radionuclide imaging/surgery</keyword><keyword>Cholecystectomy, Laparoscopic</keyword><keyword>*Cholecystokinin</keyword><keyword>Female</keyword><keyword>Follow-Up Studies</keyword><keyword>Gallbladder/pathology/physiopathology/*radionuclide imaging</keyword><keyword>Humans</keyword><keyword>*Imino Acids</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Pain</keyword><keyword>Predictive Value of Tests</keyword><keyword>Technetium</keyword><keyword>Treatment Outcome</keyword></keywords><dates><year>2011</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>1873-4626 (Electronic)
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ADDIN EN.CITE.DATA [25,26]. Lyons et al reported that 44 children with a stringent GBEF cut-off limit at < 11% had the resolution of symptoms after cholecystectomy ADDIN EN.CITE <EndNote><Cite><Author>Lyons</Author><Year>2011</Year><RecNum>30</RecNum><DisplayText>[27]</DisplayText><record><rec-number>30</rec-number><foreign-keys><key app="EN" db-id="t09ara25evxzp2etsasptapzar5w05wvszt0" timestamp="1467242188">30</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lyons, H.</author><author>Hagglund, K. H.</author><author>Smadi, Y.</author></authors></contributors><auth-address>St John Hospital and Medical Center, Detroit, MI, USA. hernando.lyons@</auth-address><titles><title>Outcomes after laparoscopic cholecystectomy in children with biliary dyskinesia</title><secondary-title>Surg Laparosc Endosc Percutan Tech</secondary-title></titles><periodical><full-title>Surg Laparosc Endosc Percutan Tech</full-title></periodical><pages>175-8</pages><volume>21</volume><number>3</number><keywords><keyword>Adolescent</keyword><keyword>Biliary Dyskinesia/epidemiology/*surgery</keyword><keyword>Child</keyword><keyword>Cholecystectomy, Laparoscopic/*methods</keyword><keyword>Female</keyword><keyword>Follow-Up Studies</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Michigan/epidemiology</keyword><keyword>Prevalence</keyword><keyword>Retrospective Studies</keyword><keyword>Surveys and Questionnaires</keyword><keyword>Time Factors</keyword><keyword>Treatment Outcome</keyword><keyword>Young Adult</keyword></keywords><dates><year>2011</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>1534-4908 (Electronic)
1530-4515 (Linking)</isbn><accession-num>21654301</accession-num><urls><related-urls><url>;[27]. However, there was no observed correlation between with GBEF and the presence of gallbladder pathology such as cholecystitis, cholelithiasis, or cholesterolosis ADDIN EN.CITE <EndNote><Cite><Author>Jones</Author><Year>2016</Year><RecNum>31</RecNum><DisplayText>[28]</DisplayText><record><rec-number>31</rec-number><foreign-keys><key app="EN" db-id="t09ara25evxzp2etsasptapzar5w05wvszt0" timestamp="1467242343">31</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Jones, P. M.</author><author>Rosenman, M. B.</author><author>Pfefferkorn, M. D.</author><author>Rescorla, F. J.</author><author>Bennett, W. E., Jr.</author></authors></contributors><auth-address>*Bronson Pediatric Gastroenterology, Bronson Children's Hospital, Kalamazoo, MichigandaggerSection of Children's Health Services Researchdouble daggerSection of Pediatric and Adolescent Comparative Effectiveness Research, Department of Pediatrics section signSection of Pediatric Surgery, Department of Surgery||Regenstrief Institute, Indiana University School of Medicine, Indianapolis.</auth-address><titles><title>Gallbladder Ejection Fraction Is Unrelated to Gallbladder Pathology in Children and Adolescents</title><secondary-title>J Pediatr Gastroenterol Nutr</secondary-title></titles><periodical><full-title>J Pediatr Gastroenterol Nutr</full-title></periodical><pages>71-5</pages><volume>63</volume><number>1</number><dates><year>2016</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>1536-4801 (Electronic)
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ADDIN EN.CITE.DATA [29] reported symptom improvement by 82% of 153 children with FGBD undergoing cholecystectomy regardless of their GBEF values. The number of children undergoing cholecystectomy has increased in the past decade ADDIN EN.CITE <EndNote><Cite><Author>Walker</Author><Year>2013</Year><RecNum>33</RecNum><DisplayText>[30]</DisplayText><record><rec-number>33</rec-number><foreign-keys><key app="EN" db-id="t09ara25evxzp2etsasptapzar5w05wvszt0" timestamp="1467242406">33</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Walker, S. K.</author><author>Maki, A. C.</author><author>Cannon, R. M.</author><author>Foley, D. S.</author><author>Wilson, K. M.</author><author>Galganski, L. A.</author><author>Wiesenauer, C. A.</author><author>Bond, S. J.</author></authors></contributors><auth-address>From the Hiram C. Polk, Jr., M.D. Department of Surgery, Division of Pediatric Surgery, University of Louisville, Louisville, KY.</auth-address><titles><title>Etiology and incidence of pediatric gallbladder disease</title><secondary-title>Surgery</secondary-title></titles><periodical><full-title>Surgery</full-title></periodical><pages>927-31; discussion 931-3</pages><volume>154</volume><number>4</number><keywords><keyword>Adolescent</keyword><keyword>Body Mass Index</keyword><keyword>Child</keyword><keyword>Cholangiopancreatography, Endoscopic Retrograde</keyword><keyword>Cholecystectomy</keyword><keyword>Female</keyword><keyword>Gallbladder Diseases/epidemiology/*etiology/surgery</keyword><keyword>Humans</keyword><keyword>Imino Acids</keyword><keyword>Incidence</keyword><keyword>Male</keyword><keyword>Retrospective Studies</keyword></keywords><dates><year>2013</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>1532-7361 (Electronic)
0039-6060 (Linking)</isbn><accession-num>24074432</accession-num><urls><related-urls><url>;[30]. Despite the safety of laparoscopic cholecystectomy in children, a different risk-benefit ratio should be considered in children with suspected FGBD ADDIN EN.CITE <EndNote><Cite><Author>Srinath</Author><Year>2014</Year><RecNum>34</RecNum><DisplayText>[31]</DisplayText><record><rec-number>34</rec-number><foreign-keys><key app="EN" db-id="t09ara25evxzp2etsasptapzar5w05wvszt0" timestamp="1467242451">34</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Srinath, A.</author><author>Saps, M.</author><author>Bielefeldt, K.</author></authors></contributors><titles><title>Biliary dyskinesia in pediatrics</title><secondary-title>Pediatr Ann</secondary-title></titles><periodical><full-title>Pediatr Ann</full-title></periodical><pages>e83-8</pages><volume>43</volume><number>4</number><keywords><keyword>Adolescent</keyword><keyword>*Biliary Dyskinesia/diagnosis/physiopathology/surgery</keyword><keyword>Child</keyword><keyword>*Cholecystectomy, Laparoscopic</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Young Adult</keyword></keywords><dates><year>2014</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0090-4481 (Print)
0090-4481 (Linking)</isbn><accession-num>24716563</accession-num><urls><related-urls><url>;[31]. Figure 4 demonstrates the algorithm for the best practice management approach in children with suspected FGBD based on our literature review.There are several limitations in the present study. The sample size was small. Since the survey was voluntary, the respondents were able to withdraw the participation of the questionnaire at any time. Although almost all respondents (99%) responded to Q1, the ambiguity of the question may attribute to the lower response rates in the subsequent questions. FGBD may not be the condition that respondents regularly treat and, therefore, up to one-third of respondents skipped questions without explanations or comments. For Q5-6, the information on the techniques and the cut-off limits of the CCK-CS used at their institutions may not have been available at the time they performed the questionnaire survey. In our opinion, none of these diagnostic modalities are absolute for the diagnosis of FGBD. ?Ultimately the decision making for cholecystectomy should be?individualized as some patients?suffer from?severe abdominal pain despite aggressive pain management (Figure 4).?As many?children who are diagnosed?with FGBD may?experience recurrent symptoms even?after cholecystectomy, they often follow up with pediatric gastroenterologists or pediatricians and?do not have a follow-up with the surgeons who operate them. Therefore, we recommend them to continue to follow up with both pediatric gastroenterologists and surgeons?as a team approach?that if?no recurrent symptoms are?observed?within a year after cholecystectomy,?the diagnosis of FDGB is confirmed.The diversity in decision-making among pediatric gastroenterologist respondents in managing the child in this clinical vignette was observed at each step in the questionnaire. A decision for the referral for cholecystectomy should be carefully considered on an individual case basis. The consensus for the guideline in managing children with FGBD may require a team effort among pediatric gastroenterologists, nuclear medicine radiologists, and pediatric surgeons. A multicenter clinical trial study may be necessary to collect longitudinal data in children diagnosed with FGBD. This collaboration will likely shed light on the natural history and the outcome of FGBD in children.ACKNOWLEDGEMENTS?The authors thank all the participants from the PEDGI bulletin board for completing the questionnaires and Robert Whinnery for the manuscript assistance.? COMMENTSBackgroundThe rates of cholecystectomy are rising in children with biliary dyskinesia or functional gallbladder disorder (FGBD). FGBD may be a cause of chronic abdominal pain in children and is a diagnosis of exclusion. Not all symptoms of FGBD disappeared after cholecystectomy. The cut-off limits of a gallbladder ejection fraction of the cholecystokinin-scintigraphy scan (CCK-CS) are the key to the diagnosis and the treatment of FGBD. This raises the issue of the accurate interpretation of the test and a thorough investigation to exclude other diseases which have symptoms like FGBD. The study was to explore discrepancy of decision making in managing a case, a scenario of which is consistent with FGBD. Research frontiersFGBD is one of the challenging fields in pediatrics. Symptoms overlap with other gastrointestinal disorders such as functional dyspepsia. Limited knowledge in this field of FGBD in children is currently observed in the current medical literature for interpretation of safety and efficacy of the investigations and treatment. There is a need for consensus on symptoms defining and a test diagnosing FGBD. Children with suspected FGBD requires a team approach with primary care physicians, pediatric gastroenterologists and pediatric surgeons. A multicenter randomized controlled trial study comparing medical vs surgical management will shed more light to understand the natural history of FGBD. There are several limitations in the present study. The sample size was small. Since the survey was voluntary, the respondents were able to withdraw the participation of the questionnaire at any time. Although almost all respondents (99%) responded to Q1, the ambiguity of the question may attribute to the lower response rates in the subsequent questions. FGBD may not be the condition that respondents regularly treat and, therefore, up to one-third of respondents skipped questions without explanations or comments. For Q5-6, the information on the techniques and the cut-off limits of the CCK-CS used at their institutions may not have been available at the time they performed the questionnaire survey. Innovations and breakthroughsThis is a pilot study using questionnaire-based survey distributed to the PEDGI Bulletin Board accessible by hundreds of pediatric gastroenterologists worldwide. The PEDGI Bulletin Board is the internet list server that encourages pediatric gastroenterologists and hepatologists worldwide to communicate with one another electronically. FGBD is a rare disease in children. A multicenter randomized controlled trial study comparing medical versus surgical management is possible and feasible through the collaborations of a broader network among primary care physicians, pediatric gastroenterologists and pediatric surgeons. ApplicationsBased on the result from this study, there was diversity in decision-making among pediatric gastroenterologist respondents in managing the child in this clinical vignette was observed at each step in the questionnaire. A decision for the referral for cholecystectomy should be carefully considered on an individual case basis. TerminologyOther terminologies that may be used to describe FGBD include biliary dyskinesia or acalculous cholecystitis. Peer-reviewThe authors have nicely summarized the problems clinicians face with the diagnosis and treatment of Functional Gallbladder Disorder. They have also proposed a guideline to help clinicians manage this condition. I believe the publication will aid clinicians in their practice and hence should proceed. It does require minor revisions as it needs to be highlighted that cholecystectomy is ultimately a decision that needs to be made after thorough counseling of the family by the pediatric surgeon.REFERENCES1?Behar J, Corazziari E, Guelrud M, Hogan W, Sherman S, Toouli J. Functional gallbladder and sphincter of oddi disorders.?Gastroenterology?2006;?130: 1498-1509 [PMID: 16678563 DOI: 10.1053/j.gastro.2005.11.063]2?Vegunta RK, Raso M, Pollock J, Misra S, Wallace LJ, Torres A, Pearl RH. 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Cholecystectomy for suspected gallbladder dyskinesia.?Cochrane Database Syst Rev?2009; (1): CD007086 [PMID: 19160318 DOI: 10.1002/14651858.CD007086.pub2]26 Krishnamurthy GT, Krishnamurthy S: Extended application of 99mTc-mebrofenin cholescintigraphy with cholecystokinin in the evaluation of abdominal pain of hepatobiliary and gastrointestinal origin. Nucl Med Commun 2010; 31: 346-354 [DOI: 10.1097/MNM.0b013e32832fa2c0]27?Lyons H, Hagglund KH, Smadi Y. Outcomes after laparoscopic cholecystectomy in children with biliary dyskinesia.?Surg Laparosc Endosc Percutan Tech?2011;?21: 175-178 [PMID: 21654301 DOI: 10.1097/SLE.0b013e31821db7b2]28?Jones PM, Rosenman MB, Pfefferkorn MD, Rescorla FJ, Bennett WE. Gallbladder Ejection Fraction Is Unrelated to Gallbladder Pathology in Children and Adolescents.?J Pediatr Gastroenterol Nutr?2016;?63: 71-75 [PMID: 26670710 DOI: 10.1097/MPG.0000000000001065]29?Mahida JB, Sulkowski JP, Cooper JN, King AP, Deans KJ, King DR, Minneci PC. Prediction of symptom improvement in children with biliary dyskinesia.?J Surg Res?2015;?198: 393-399 [PMID: 25891671 DOI: 10.1016/j.jss.2015.03.056]30?Walker SK, Maki AC, Cannon RM, Foley DS, Wilson KM, Galganski LA, Wiesenauer CA, Bond SJ. Etiology and incidence of pediatric gallbladder disease.?Surgery?2013;?154: 927-31; discussion 931-3 [PMID: 24074432 DOI: 10.1016/j.surg.2013.04.040]31?Srinath A, Saps M, Bielefeldt K. Biliary dyskinesia in pediatrics.?Pediatr Ann?2014;?43: e83-e88 [PMID: 24716563 DOI: 10.3928/00904481-20140325-09]P-Reviewer: Singhal V, Wang R S-Editor: Qi Y L-Editor: E-Editor:Figure 1 Questionnaire for pediatric gastroenterologists to assess a case with chronic right upper quadrant pain. EGD: Esophagogastroduodenoscopy; UGI: Upper GI Study; U/S: Ultrasonography; MRI: Magnetic Resonance Imaging; CCK-CS: Cholecystokininscintigraphy scan.Figure 2 Investigations for chronic right upper quadrant pain in children.Figure 3 Criteria for referral for a surgical evaluation. GBEF: Gallbladder ejection fraction; CCK: Cholecystokinin; RUQ: Right Upper Quadrant; CCK-CS: Cholecystokinin scintigraphy scan. Figure 4 Algorithm for the best practice management approach in children with suspected functional gallbladder disorder (Reference 1). FGBD: Functional gallbladder disorder; RUQ: Right Upper Quadrant; GBEF: Gall Bladder ejection fraction; CCK: Cholecystokinin; GERD: Gastroesophageal reflux disease; PPI: Proton pump inhibitor; MRCP: Magnetic resonance cholangipancreatography; ERCP: Endoscopic retrograde cholangipancreatography.Table 1 Cut-off limits of gallbladder ejection fraction used for criteria to diagnose abnormal gallbladder function. Values under responses represent number of responses for each gallbladder ejection fraction cutoff% GBEF used as cut-off Responses < 40% 17 (20) < 35% 47 (55) < 30% 3 (3.5) < 25% 4 (4.7) < 16% 2 (2.4) < 15% 2 (2.4) ................
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