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Background and Aims: Since 1985, the American Society for Gastrointestinal Endoscopy (ASGE) has awarded grants for endoscopic-related research. The goals of this study were to examine trends in ASGE grant funding and to assess productivity of previous recipients of the ASGE grant awards., Methods: This was a retrospective cohort analysis of all research grants awarded by the ASGE through 2009. Measures of academic productivity and self-assessment of the ASGE awards' impact on the recipients' careers were defined by using publicly available resources (eg, National Library of Medicine-PubMed) and administration of an electronic survey to award recipients., Results: The ASGE awarded 304 grants totaling $12.5 million to 214 unique awardees. Funding increased 7.5-fold between 1985 and 1989 (mean $102,000/year) and between 2005 and 2009 (mean $771,000/year). The majority of awardees were men (83%), were at or below the level of assistant professor (82%), with a median of 3 years of postfellowship experience at the time of the award, and derived from a broad spectrum of institutions as measured by National Institutes of Health funding rank (median 26, interquartile range [IQR] 12-64). Nineteen percent had a master's degree in a research-related field. Awardees' median publications per year increased from 3.5 (IQR 1.2-9.0) before funding to 5.7 (IQR 1.8-9.5) since funding; P = .04, and median h-index scores increased from 3 (IQR 1-8) to 17 (IQR 8-26); P < .001. Multivariate analysis found that the presence of a second advanced degree (eg, masters or doctorate) was independently predictive of high productivity (odds ratio [OR] 2.92; 95% confidence interval [CI], 1.09-7.81). Among 212 unique grant recipients, 82 (40%) completed the online survey. Of the respondents, median peer-reviewed publications per year increased from 3.4 (IQR 1.9-5.5) to 4.5 (IQR 2.0-9.5); P = .17. Ninety-one percent reported that the ASGE grant had a positive or very positive impact on their careers, and 85% of respondents are currently practicing in an academic environment. Most of the grants resulted in at least 1 peer-reviewed publication (67% per Internet-based search and 81% per survey)., Conclusions: The ASGE research program has grown considerably since 1985, with the majority of grants resulting in at least 1 grant-related publication. Overall academic productivity increased after the award, and the majority of awardees report a positive or very positive impact of the award on their careers. Medical professional societies are an important sponsor of clinical research., (Copyright © 2016. Published by Elsevier Inc.)

Objective: Historically, chronic pancreatitis (CP) was considered a disease of alcoholic males, but recent data suggest its etiology to be complex. To better understand CP in women, we compared data on women and men with CP in a large, prospectively ascertained multicenter US cohort., Methods: Patients with CP enrolled in the NAPS2 Continuation and Validation study were studied. Information on demographics, etiology, risk factors, phenotype, and treatment(s) used was obtained from detailed questionnaires completed by the patients and physicians., Results: Of 521 cases, 45% were women. Women were significantly (P < 0.05) less likely to have alcohol etiology (30% vs 58.5%) and more likely to have nonalcoholic etiologies (idiopathic, 32% vs 18%; obstructive, 12% vs 2.4%; genetic, 12.8% vs 7.3%). Demographics, pain experience, morphologic findings, exocrine and endocrine insufficiency, CP-related disability, and use of medical therapies were mostly similar in both sexes. Sphincterotomy (biliary, 33% vs 24%; pancreatic, 38% vs 28%; P < 0.05) was performed more frequently in women, whereas cyst/pseudocyst operations were more common in men (6.6 vs 2.6%, P = 0.02)., Conclusions: Most CP cases in women are from nonalcoholic etiologies. In contrast to many other chronic diseases, clinical phenotype of CP is determined by the disease and is independent of sex.

Objectives: Chronic pancreatitis is a significant medical problem that impacts a large number of patients worldwide. In 2014, we developed a disease-specific instrument for the evaluation of quality of life in this group of patients: pancreatitis quality of life instrument (PANQOLI). The goal of this study was to evaluate its psychometric properties: its reliability and its construct validity., Methods: This is a cross-sectional multi-center study that involved 12 pancreatic disease centers. Patients who met the inclusion/exclusion criteria for chronic pancreatitis were invited to participate. Those who accepted were asked to complete seven questionnaires/instruments. Only patients who completed the PANQOLI were included in the study. Its reliability and its construct validity were tested., Results: A total of 159 patients completed the PANQOLI and were included in the study. They had a mean age of 49.03, 49% were male, and 84% were Caucasian. Six of the 24 items on the scale were removed because of lack of inter-item correlation, redundancy, or lack of correlation to quality of life issues. The final 18-item scale had excellent reliability (Cronbach's alpha coefficient: 0.914) and excellent construct validity with good correlation to generic quality of life instruments (SF-12 and EORTC QLQ-C30/QLQ-PAN26) and lack of correlation to non-quality of life instruments (MAST and DAST). Through exploratory factor analysis, the PANQOLI was found to consist of four subscales: emotional function scale, role function scale, physical function scale, and "self-worth" scale., Conclusions: PANQOLI is the first disease-specific instrument to be developed and validated for the evaluation of quality of life in chronic pancreatitis patients. It has a unique subscale for "self-worth" that differentiates it from other generic instruments. Studies are currently under way to evaluate its use in other populations not included in this study.

Background and Aims: Endoscopic ultrasound-guided biliary drainage (EUS-BD) has emerged as an alternative to traditional radiologic and surgical drainage procedures after failed endoscopic retrograde cholangiopancreatography (ERCP). However, prospective multicenter data are lacking. The aims of this study were to prospectively assess the short- and long-term efficacy and safety of EUS-BD in patients with malignant distal biliary obstruction., Patients and Methods: Consecutive patients at 12 tertiary centers (5 US, 5 European, 1 Asian, 1 South American) with malignant distal biliary obstruction and failed ERCP underwent EUS-BD. Technical success was defined as successful stent placement in the desired position. Clinical success was defined as a reduction in bilirubin by 50 % at 2 weeks or to below 3 mg/dL at 4 weeks. Adverse events were prospectively tracked and graded according to the American Society for Gastrointestinal Endoscopy (ASGE) lexicon's severity grading system. Overall survival and duration of stent patency were calculated using Kaplan-Meier analysis., Results: A total of 96 patients (mean age 66 years, female 45 %, pancreatic cancer 55 %) underwent EUS-BD. Stent placement (technical success) was achieved in 92 (95.8 %) patients (metallic stent 84, plastic stent 8). Mean procedure time was 40 minutes. Clinical success was achieved in 86 (89.5 %) patients. A total of 10 (10.5 %) adverse events occurred: pneumoperitoneum (n = 2), sheared wire (n = 1), bleeding (n = 1), bile leak (n = 3), cholangitis (n = 2), and unintentional perforation (n = 1); 4 graded as mild, 4 moderate, 1 severe, and 1 fatal (due to perforation). A total of 38 (44 %) patients died of disease progression during the study period. The median patient survival was 167 days (95 %CI 112 - 221) days. The 6-month stent patency rate was 95 % (95 %CI 94.94 - 95.06 %) and the 1-year stent patency was 86 % (95 %CI 85.74 - 86.26 %)., Conclusion: This study on EUS-BD demonstrates excellent efficacy and safety of EUS-BD when performed by experts., Study Registration: NCT01889953.

Importance: Endoscopic placement of multiple plastic stents in parallel is the first-line treatment for most benign biliary strictures; it is possible that fully covered, self-expandable metallic stents (cSEMS) may require fewer endoscopic retrograde cholangiopancreatography procedures (ERCPs) to achieve resolution., Objective: To assess whether use of cSEMS is noninferior to plastic stents with respect to stricture resolution., Design, Setting, and Participants: Multicenter (8 endoscopic referral centers), open-label, parallel, randomized clinical trial involving patients with treatment-naive, benign biliary strictures (N = 112) due to orthotopic liver transplant (n = 73), chronic pancreatitis (n = 35), or postoperative injury (n = 4), who were enrolled between April 2011 and September 2014 (with follow-up ending October 2015). Patients with a bile duct diameter less than 6 mm and those with an intact gallbladder in whom the cystic duct would be overlapped by a cSEMS were excluded., Interventions: Patients (N = 112) were randomized to receive multiple plastic stents or a single cSEMS, stratified by stricture etiology and with endoscopic reassessment for resolution every 3 months (plastic stents) or every 6 months (cSEMS). Patients were followed up for 12 months after stricture resolution to assess for recurrence., Main Outcomes and Measures: Primary outcome was stricture resolution after no more than 12 months of endoscopic therapy. The sample size was estimated based on the noninferiority of cSEMS to plastic stents, with a noninferiority margin of -15%., Results: There were 55 patients in the plastic stent group (mean [SD] age, 57 [11] years; 17 women [31%]) and 57 patients in the cSEMS group (mean [SD] age, 55 [10] years; 19 women [33%]). Compared with plastic stents (41/48, 85.4%), the cSEMS resolution rate was 50 of 54 patients (92.6%), with a rate difference of 7.2% (1-sided 95% CI, -3.0% to ∞; P < .001). Given the prespecified noninferiority margin of -15%, the null hypothesis that cSEMS is less effective than plastic stents was rejected. The mean number of ERCPs to achieve resolution was lower for cSEMS (2.14) vs plastic (3.24; mean difference, 1.10; 95% CI, 0.74 to 1.46; P < .001)., Conclusions and Relevance: Among patients with benign biliary strictures and a bile duct diameter 6 mm or more in whom the covered metallic stent would not overlap the cystic duct, cSEMS were not inferior to multiple plastic stents after 12 months in achieving stricture resolution. Metallic stents should be considered an appropriate option in patients such as these., Trial Registration: clinicaltrials.gov Identifier: NCT01221311.

Background: The combination of prophylactic pancreatic stent placement (PSP) - a temporary plastic stent placed in the pancreatic duct - and rectal non-steroidal anti-inflammatory drugs (NSAIDs) is recommended for preventing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in high-risk cases. Preliminary data, however, suggest that PSP may be unnecessary if rectal NSAIDs are administered. Given the costs and potential risks of PSP, we aim to determine whether rectal indomethacin obviates the need for pancreatic stent placement in patients undergoing high-risk ERCP., Methods/design: The SVI (Stent vs. Indomethacin) trial is a comparative effectiveness, multicenter, randomized, double-blind, non-inferiority study of rectal indomethacin alone versus the combination of rectal indomethacin and PSP for preventing PEP in high-risk cases. One thousand four hundred and thirty subjects undergoing high-risk ERCP, in whom PSP is planned solely for PEP prevention, will be randomized to indomethacin alone or combination therapy. Those who are aware of study group assignment, including the endoscopist, will not be involved in the post-procedure care of the patient for at least 48 hours. Subjects will be assessed for PEP and its severity by a panel of independent and blinded adjudicators. Indomethacin alone will be declared non-inferior to combination therapy if the two-sided 95 % upper confidence bound of the treatment difference is less than 5 % between the two groups. Biological specimens will be obtained from trial participants and centrally banked., Discussion: The SVI trial is designed to determine whether PSP remains necessary in the era of NSAIDs pharmacoprevention. The associated bio-repository will establish the groundwork for important scientific breakthrough., Trial Registration: NCT02476279, registered June 2015.

Goal: We aimed to summarize pooled rebleeding rates of angioectasia after therapeutic endoscopy, and compare these to historical control (no intervention) rates., Background: Obscure gastrointestinal bleeding continues to be challenging to diagnose and treat; in America, small bowel angioectasias are the most common cause. Technology advances led to higher diagnostic yield for these lesions; however, therapeutic impact of endoscopy remains unclear., Study: A PubMed search (June 1, 2006 to September 19, 2013) with 2 independent reviews sought articles reporting rebleeding rates of symptomatic angioectasia without therapy (natural history) and after endoscopic treatment. This study list was added to studies in the 2007 American Gastroenterological Association systematic review. Data on number of patients who underwent endoscopic therapy, type of therapy used, number of patients who experienced rebleeding, and follow-up time were extracted. Rebleeding data were pooled and weighted averages were reported with 95% confidence intervals (CI)., Results: Twenty-four articles (n=490 patients) with data on endoscopic therapy for angioectasia and 6 natural history cohorts (n=130) receiving no therapy for angioectasia were eligible. Of the endoscopic therapy patients, 121 at push enteroscopy and 427 at balloon-assisted enteroscopy; 209/490 (42.7%; 95% CI, 38%-47%) rebled. Of the control (no therapy) patients, 64/130 (49.2%; 95% CI, 40%-58%) rebled. Number needed to treat is estimated at 15 to 16., Conclusions: Rebleeding rate after endoscopic therapy for symptomatic small bowel angioectasia may be comparable to that expected without therapy. Endoscopic therapy may be ineffective; if effective, the needed to treat is estimated to be high. Controlled studies, with intervention-stratified and etiology-stratified outcomes are needed.

Background and Study Aim: Pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP) is a significant and potentially life-threatening adverse event and is common in patients with suspected sphincter of Oddi dysfunction (SOD). Here we aimed to identify predictors of the risk in this population., Patients and Methods: The Evaluating Predictors and Interventions in SOD (EPISOD) study prospectively enrolled 214 post-cholecystectomy patients with SOD type III in seven US centers. Patients were randomized, using a 2:1 allocation, to sphincterotomy or sham procedure, irrespective of the results of sphincter of Oddi manometry. Patients in the sphincterotomy arm who had elevated pancreatic sphincter pressure were randomized to biliary only or to dual (biliary and pancreatic) sphincterotomy. All but one patient received prophylactic pancreatic stents, but none received pharmacological prophylaxis. Post ERCP pancreatitis (PEP) was defined as acute pancreatitis within the subsequent 7 days. Blinded research coordinators at each site called patients at 1 week post-procedure., Results: PEP occurred in 26 patients, in 10.6 % (15/141) in the sphincterotomy arm and 15.1 % (11/73) in the sham arm; unadjusted relative risk 0.71 (95 % confidence interval [95 %CI] 0.34 - 1.46). PEP rate was not significantly different in patients who received sphincterotomy compared with those undergoing sham treatment. In addition, the proportion was not statistically different in those who received biliary sphincterotomy alone (12/94; 12.8 % [95 %CI 6.0 % - 19.5 %]) compared with dual sphincterotomy (3/47; 6.4 % [95 %CI 0.0 % - 13.4 %]). Multivariate analysis identified an interaction between duration of ERCP and sedation type (P < 0.02)., Conclusion: The performance of biliary or dual sphincterotomy does not increase the risk of PEP in patients suspected of SOD. However, the high rate of PEP in patients with suspected SOD, despite pancreatic stenting in expert centers, is confirmed in this prospective study. The combined effect of duration of ERCP and sedation type on the development of PEP should be further explored.Clinicaltrials.gov registration: NCT00688662., (© Georg Thieme Verlag KG Stuttgart · New York.)

Sphincter of Oddi dysfunction (SOD) has long been a controversial topic, starting with whether it even exists, as a sphincterotomy-responsive entity to treat, for either: (1) post-cholecystectomy abdominal pain and/or (2) idiopathic recurrent acute pancreatitis (IRAP). Many of its aspects had required further research to better prove or refute its existence and to provide proper recommendations for physicians to diagnose and treat this condition. Fortunately, there has been major advancement in our knowledge in several areas over the past few years. New studies on challenging the classification, exploring alternative diagnostic methods, and quantifying the role of sphincterotomy in treatment of SOD for post-cholecystectomy pain and for IRAP were recently published, including a randomized trial in each of the two areas. The goal of this paper is to review recent literature on selected important questions and to summarize the results of major trials in this field.

Background: Single-balloon enteroscopy (SBE) was introduced in 2007 to diagnose and treat small-bowel disorders. No study to date has evaluated SBE in patients with surgically altered anatomy outside of ERCP., Objective: To evaluate the efficacy, yield, and safety of SBE in patients with surgically altered anatomy., Design: Retrospective study., Setting: Tertiary-care academic medical center., Patients: All patients with altered surgical anatomy who underwent SBE at the Medical University of South Carolina from July 2007 to September 2013., Interventions: SBE., Main Outcome Measurements: Diagnostic yield, therapeutic yield, technical success, and adverse events., Results: A total of 48 patients met inclusion criteria. Mean age was 56 years (77% female). Eleven patients underwent single-balloon PEG placement, 8 single-balloon ERCP, 22 non-PEG/non-ERCP anterograde SBE, and 7 retrograde SBE. Previous surgeries included Roux-en-Y gastric bypass (n=26), small-intestine resection (n=6), colon resection (n=5), Whipple procedure (n=4), choledochojejunostomy (n=3), hepaticojejunostomy (n=1), Billroth I (n=1), Billroth II (n=1), and Puestow procedure (n=1). Procedural indications were PEG tube placement (n=11), choledocholithiasis (n=2), biliary stricture (n=2), obstructive jaundice (n=1), cholangitis (n=1), ampullary mass (n=1), sphincter of Oddi dysfunction (n=1), anemia and/or bleeding (n=15), abdominal pain (n=9), radiologic evidence of obstruction (n=3), and Peutz-Jeghers syndrome (n=2). The technical success rate was 73% in single-balloon PEG placement, 88% in single-balloon ERCP, 82% in other anterograde SBEs, and 86% in retrograde SBEs. No intraprocedural or postprocedural adverse events were observed., Limitations: Single center, retrospective study., Conclusion: SBE is safe and effective in patients with surgically altered anatomy., (Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background & Aims: There is controversy over the efficacy of pharmacologic agents for preventing pancreatitis after endoscopic retrograde cholangiopancreatography (PEP). We performed a systematic review of PEP pharmacoprevention to evaluate safety and efficacy., Methods: We performed a systematic search of the literature for randomized controlled trials (RCTs) and meta-analyses of PEP pharmacoprevention through February 2014. After identifying relevant studies, 2 reviewers each extracted information on study characteristics, clinical outcomes, and risk of bias. A research classification scale was developed to identify pharmacologic agents ready for clinical use, agents for which a confirmatory RCT should be considered a high priority, agents for which exploratory studies are still necessary, and agents for which additional research should be of low priority. Clinical and research recommendations for each agent were made by consensus after considering research classification results and other important factors such as magnitude of benefit, safety, availability, and cost., Results: After screening 851 citations and 263 potentially relevant articles, 2 reviewers identified 85 RCTs and 28 meta-analyses that were eligible. On the basis of these studies, rectal nonsteroidal anti-inflammatory drugs were found to be appropriate for clinical use, especially for high-risk cases. Sublingual nitroglycerin, bolus-administered somatostatin, and nafamostat were found to be promising agents for which confirmatory research is warranted. Additional research was found to be required to justify confirmatory RCTs for topical epinephrine, aggressive intravenous fluids, gabexate, ulinastatin, secretin, and antibiotics., Conclusions: On the basis of a systematic review, NSAIDs are appropriate for use in prevention of PEP, especially for high-risk cases. Additional research is necessary to clarify the role of other pharmacologic agents. These findings could inform future research and guide clinical decision-making and policy., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Most patients presenting with symptoms of esophageal cancer (EC) have advanced disease. Even with resection, the cure rate is extremely low due to local recurrence and metastatic disease. Early detection and effective therapeutic intervention are essential to improve survival., Aims: This study tested the hypothesis that the presence of EC modulates concentrations of specific plasma proteins and peptides, potentially allowing discrimination between EC and controls based on mass spectrometric analysis of the respective plasma proteomes., Methods: Blood samples from 79 esophageal cancer patients and 40 age-matched normal subjects were processed to plasma, and protein/peptide sub-fractions were isolated using HIC8 or WAX-derivatized superparamagnetic beads. Triplicate matrix-assisted laser desorption time-of-flight mass spectra were acquired for specific plasma fractions from each subject., Results: HIC8 and WAX-derivatized plasma eluates yielded 79 and 77 candidate features, respectively, and a Random Forest algorithm identified a subset of features whose peak intensities allowed discrimination between cancer patients and controls. Areas under the curve in receiver operating characteristic curves for HIC8 spectra were 0.88 and 0.83 for WAX spectra. The combined feature set discriminated EC from control plasma with 79 % sensitivity and 79 % specificity, with positive and negative test likelihood ratios of >14 and 0.17, respectively., Conclusions: These data lay the foundation for the development of a clinically useful test for esophageal cancer based on statistical analysis of proteomic spectra of patient plasma samples. This approach will be validated by analysis of larger patient cohorts, development of cancer-specific classifiers, and assessment of racial origin imbalances.

Background & Aims: Chronic pancreatitis is characterized by inflammation, atrophy, fibrosis with progressive ductal changes, and functional changes that include variable exocrine and endocrine insufficiency and multiple patterns of pain. We investigated whether abdominal imaging features accurately predict patterns of pain., Methods: We collected data from participants in the North American Pancreatitis Study 2 Continuation and Validation, a prospective multicenter study of patients with chronic pancreatitis performed at 13 expert centers in the United States from July 2008 through March 2012. Chronic pancreatitis was defined based on the detection of characteristic changes by cross-sectional abdominal imaging, endoscopic retrograde cholangiopancreatography, endoscopic ultrasonography, or histology analyses. Patients were asked by a physician or trained clinical research coordinator if they had any abdominal pain during the year before enrollment, those who responded "yes" were asked to select from a list of 5 pain patterns. By using these patterns, we classified patients' pain based on timing and severity. Abnormal pancreatitis-associated features on abdominal imaging were recorded using standardized case report forms., Results: Data were collected from 518 patients (mean age, 52 ± 14.6 y; 55% male; and 87.6% white). The most common physician-identified etiologies were alcohol (45.8%) and idiopathic (24.3%); 15.6% of patients reported no abdominal pain in the year before enrollment. The most common individual pain pattern was described as constant mild pain with episodes of severe pain and was reported in 45% of patients. The most common imaging findings included pancreatic ductal dilatation (68%), atrophy (57%), and calcifications (55%). Imaging findings were categorized as obstructive for 20% and as inflammatory for 25% of cases. The distribution of individual imaging findings was similar among patients with different patterns of pain. The distribution of pain patterns did not differ among clinically relevant groups of imaging findings., Conclusions: Mechanisms that determine patterns and severity of pain in patients with chronic pancreatitis are largely independent of structural variants observed by abdominal imaging techniques. Pancreas-relevant quantitative and qualitative pain measures should be included in the evaluation of patients with chronic pancreatitis to assess pain severity independently of imaging findings., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: It is believed, based on limited observational data, that an unsuccessful attempt to place a prophylactic pancreatic stent substantially increases the risk of post-ERCP pancreatitis (PEP)., Objective: To better understand the risk of PEP in patients with failed pancreatic stent placement (FPS) and the impact of rectal indomethacin on this risk., Design: Secondary analysis of randomized, controlled trial data., Setting: University of Michigan and Indiana University., Patients: A total of 577 clinical trial participants at elevated risk for PEP., Interventions: Pancreatic stent placement., Main Outcome Measurements: Within the placebo group, we compared PEP rates in patients with FPS, patients who underwent successful stent placement, and in those without a stent attempt. We also performed a regression analysis evaluating the association between FPS and PEP. To define the protective effect of indomethacin, we repeated these analyses in the indomethacin group and in the full study cohort., Results: The incidence of PEP among patients in the placebo group who experienced FPS was 34.7%, significantly exceeding rates in patients who underwent successful stent placement (16.4%) and in those without a stent attempt (12.1%). After we adjusted for known PEP risk factors, FPS was found to be independently associated with PEP. Among the indomethacin group and in the full cohort, FPS was not associated with a higher risk of PEP., Limitations: Low event rate, FPS not prospectively captured., Conclusion: FPS appears to confer an increased risk of PEP, which is attenuated by rectal indomethacin administration. These findings highlight the importance of adequate training and proficiency before endoscopists attempt pancreatic stent placement and the routine use of rectal indomethacin in high-risk ERCP cases., (Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

CFTR is a dynamically regulated anion channel. Intracellular WNK1-SPAK activation causes CFTR to change permeability and conductance characteristics from a chloride-preferring to bicarbonate-preferring channel through unknown mechanisms. Two severe CFTR mutations (CFTRsev) cause complete loss of CFTR function and result in cystic fibrosis (CF), a severe genetic disorder affecting sweat glands, nasal sinuses, lungs, pancreas, liver, intestines, and male reproductive system. We hypothesize that those CFTR mutations that disrupt the WNK1-SPAK activation mechanisms cause a selective, bicarbonate defect in channel function (CFTRBD) affecting organs that utilize CFTR for bicarbonate secretion (e.g. the pancreas, nasal sinus, vas deferens) but do not cause typical CF. To understand the structural and functional requirements of the CFTR bicarbonate-preferring channel, we (a) screened 984 well-phenotyped pancreatitis cases for candidate CFTRBD mutations from among 81 previously described CFTR variants; (b) conducted electrophysiology studies on clones of variants found in pancreatitis but not CF; (c) computationally constructed a new, complete structural model of CFTR for molecular dynamics simulation of wild-type and mutant variants; and (d) tested the newly defined CFTRBD variants for disease in non-pancreas organs utilizing CFTR for bicarbonate secretion. Nine variants (CFTR R74Q, R75Q, R117H, R170H, L967S, L997F, D1152H, S1235R, and D1270N) not associated with typical CF were associated with pancreatitis (OR 1.5, p = 0.002). Clones expressed in HEK 293T cells had normal chloride but not bicarbonate permeability and conductance with WNK1-SPAK activation. Molecular dynamics simulations suggest physical restriction of the CFTR channel and altered dynamic channel regulation. Comparing pancreatitis patients and controls, CFTRBD increased risk for rhinosinusitis (OR 2.3, p<0.005) and male infertility (OR 395, p<<0.0001). WNK1-SPAK pathway-activated increases in CFTR bicarbonate permeability are altered by CFTRBD variants through multiple mechanisms. CFTRBD variants are associated with clinically significant disorders of the pancreas, sinuses, and male reproductive system.

Background: Cross-sectional imaging remains the first-line test for obstructive jaundice despite high miss rates for pancreatobiliary tumours. Improvements in resolution and slice thickness of spiral computed tomography⁄magnetic resonance imaging⁄magnetic resonance cholangiopancreatography promised to increase accuracy., Objective: To assess whether the post-test probability of neoplasm is truly altered by the presence or absence of a mass on computed tomography⁄magnetic resonance imaging in obstructive jaundice., Methods: The institutional endoscopic ultrasound (EUS) database was retrospectively reviewed to stratify patients presenting to EUS over a two-year period for obstructive jaundice (suspicious for malignancy) according to their pre-EUS imaging results. The primary analysis involved the calculation of the positive predictive value and negative predictive value (NPV) of imaging with 95% binomial CIs. Test performance of EUS⁄fine-needle aspiration (FNA) was also calculated. Final diagnosis was determined by positive cytology⁄histology; negative EUS was supplemented by clinical follow-up., Results: The positive predictive value (n = 51) and NPV (n = 53) of pre-EUS imaging was 98% (95% CI 90% to 100%) and 9% (95% CI 3% to 21%), respectively (accuracy 53%), with post-test suspicion of malignancy similar between imaging-positive and -negative groups. EUS demonstrated a mass in 96% of imaging-positive cases versus 85% in imaging-negative cases (exact P = 0.09). Malignant or suspicious FNA cytology was obtained with EUS in 92% of the imaging-positive group, and 62% of the imaging-negative group (75% of subgroup with FNA) (P < 0.001)., Conclusion: Lack of a definite mass on pre-EUS imaging had low NPV, and was clearly not sufficiently accurate or reassuring in this clinical setting. In suspicious obstructive jaundice, EUS with FNA has a high diagnostic yield regardless of the findings of pre-EUS cross-sectional imaging and, as such, EUS may be a more reasonable first-line test in this high-suspicion setting.

The Papanicolaou Society of Cytopathology has developed a set of guidelines for pancreaticobiliary cytology including indications for endoscopic ultrasound (EUS) and fine-needle aspiration (FNA) biopsy, techniques for EUS-FNA, terminology and nomenclature to be used for pancreaticobiliary disease, ancillary testing and postbiopsy management. All documents are based on expertise of the authors, literature review, discussions of the draft document at national and international meetings and synthesis of online comments of the draft document. This document selectively presents the results of these discussions. This document summarizes recommendations for the clinical and imaging work-up of pancreatic and biliary tract lesions along with indications for cytologic study of these lesions. Prebrushing and FNA requirements are also discussed.

Background: Biliopancreatic-type postcholecystectomy pain, without significant abnormalities on imaging and laboratory test results, has been categorized as "suspected" sphincter of Oddi dysfunction (SOD) type III. Clinical predictors of "manometric" SOD are important to avoid unnecessary ERCP, but are unknown., Objective: To assess which clinical factors are associated with abnormal sphincter of Oddi manometry (SOM)., Design: Prospective, cross-sectional., Setting: Tertiary., Patients: A total of 214 patients with suspected SOD type III underwent ERCP and pancreatic SOM (pSOM; 85% dual SOM), at 7 U.S. centers (from August 2008 to March 2012) as part of a randomized trial., Interventions: Pain and gallbladder descriptors, psychosocial/functional disorder questionnaires., Main Outcome Measurements: Abnormal SOM findings. Univariate and multivariate analyses assessed associations between clinical characteristics and outcome., Results: The cohort was 92% female with a mean age of 38 years. Baseline pancreatic enzymes were increased in 5%; 9% had minor liver enzyme abnormalities. Pain was in the right upper quadrant (RUQ) in 90% (48% also epigastric); 51% reported daily abdominal discomfort. Fifty-six took narcotics an average of 33 days (of the past 90 days). Less than 10% experienced depression or anxiety. Functional disorders were common. At ERCP, 64% had abnormal pSOM findings (34% both sphincters, 21% biliary normal), 36% had normal pSOM findings, and 75% had at least abnormal 1 sphincter. Demographic factors, gallbladder pathology, increased pancreatobiliary enzymes, functional disorders, and pain patterns did not predict abnormal SOM findings. Anxiety, depression, and poorer coping were more common in patients with normal SOM findings (not significant on multivariate analysis)., Limitations: Generalizability., Conclusions: Patient and pain factors and psychological comorbidity do not predict SOM results at ERCP in suspected type III SOD. (, Clinical Trial Registration Number: NCT00688662.)., (Copyright © 2014 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Objective: This study aims to describe the frequency of use and reported effectiveness of endoscopic and surgical therapies in patients with chronic pancreatitis treated at US referral centers., Methods: Five hundred fifteen patients were enrolled prospectively in the North American Pancreatitis Study 2, where patients and treating physicians reported previous therapeutic interventions and their perceived effectiveness. We evaluated the frequency and effectiveness of endoscopic (biliary or pancreatic sphincterotomy, biliary or pancreatic stent placement) and surgical (pancreatic cyst removal, pancreatic drainage procedure, pancreatic resection, surgical sphincterotomy) therapies., Results: Biliary and/or pancreatic sphincterotomy (42%) were the most common endoscopic procedure (biliary stent, 14%; pancreatic stent, 36%; P < 0.001). Endoscopic procedures were equally effective (biliary sphincterotomy, 40.0%; biliary stent, 40.8%; pancreatic stent, 47.0%; P = 0.34). On multivariable analysis, the presence of abdominal pain (odds ratio, 1.82; 95% confidence interval, 1.15-2.88) predicted endoscopy, whereas exocrine insufficiency (odds ratio, 0.63; 95% confidence interval, 0.42-0.94) deterred endoscopy. Surgical therapies were attempted equally (cyst removal, 7%; drainage procedure, 10%; resection procedure, 12%) except for surgical sphincteroplasty (4%; P < 0.001). Surgical sphincteroplasty was the least effective (46%; P < 0.001) versus cyst removal (76% drainage [71%] and resection [73%])., Conclusions: Although surgical therapies were performed less frequently than endoscopic therapies, they were more often reported to be effective.

Importance: Abdominal pain after cholecystectomy is common and may be attributed to sphincter of Oddi dysfunction. Management often involves endoscopic retrograde cholangiopancreatography (ERCP) with manometry and sphincterotomy., Objective: To determine whether endoscopic sphincterotomy reduces pain and whether sphincter manometric pressure is predictive of pain relief., Design, Setting, and Patients: Multicenter, sham-controlled, randomized trial involving 214 patients with pain after cholecystectomy without significant abnormalities on imaging or laboratory studies, and no prior sphincter treatment or pancreatitis randomly assigned (August 6, 2008-March 23, 2012) to undergo sphincterotomy or sham therapy at 7 referral medical centers. One-year follow-up was blinded. The final follow-up visit was March 21, 2013., Interventions: After ERCP, patients were randomized 2:1 to sphincterotomy (n = 141) or sham (n = 73) irrespective of manometry findings. Those randomized to sphincterotomy with elevated pancreatic sphincter pressures were randomized again (1:1) to biliary or to both biliary and pancreatic sphincterotomies. Seventy-two were entered into an observational study with conventional ERCP managemeny., Main Outcomes and Measures: Success of treatment was defined as less than 6 days of disability due to pain in the prior 90 days both at months 9 and 12 after randomization, with no narcotic use and no further sphincter intervention., Results: Twenty-seven patients (37%; 95% CI, 25.9%-48.1%) in the sham treatment group vs 32 (23%; 95% CI, 15.8%-29.6%) in the sphincterotomy group experienced successful treatment (adjusted risk difference, -15.6%; 95% CI, -28.0% to -3.3%; P = .01). Of the patients with pancreatic sphincter hypertension, 14 (30%; 95% CI, 16.7%-42.9%) who underwent dual sphincterotomy and 10 (20%; 95% CI, 8.7%-30.5%) who underwent biliary sphincterotomy alone experienced successful treatment. Thirty-seven treated patients (26%; 95% CI,19%-34%) and 25 patients (34%; 95% CI, 23%-45%) in the sham group underwent repeat ERCP interventions (P = .22). Manometry results were not associated with the outcome. No clinical subgroups appeared to benefit from sphincterotomy more than others. Pancreatitis occurred in 15 patients (11%) after primary sphincterotomies and in 11 patients (15%) in the sham group. Of the nonrandomized patients in the observational study group, 5 (24%; 95% CI, 6%-42%) who underwent biliary sphincterotomy, 12 (31%; 95% CI, 16%-45%) who underwent dual sphincterotomy, and 2 (17%; 95% CI, 0%-38%) who did not undergo sphincterotomy had successful treatment., Conclusions and Relevance: In patients with abdominal pain after cholecystectomy undergoing ERCP with manometry, sphincterotomy vs sham did not reduce disability due to pain. These findings do not support ERCP and sphincterotomy for these patients., Trial Registration: clinicaltrials.gov Identifier: NCT00688662.

The Papanicolaou Society of Cytopathology has developed a set of guidelines for pancreaticobiliary cytology including indications for endoscopic ultrasound (EUS) and fine-needle aspiration (FNA) biopsy, techniques for EUS-FNA, terminology and nomenclature to be used for pancreaticobiliary disease, ancillary testing, and post-biopsy management. All documents are based on expertise of the authors, literature review, discussions of the draft document at national and international meetings, and synthesis of online comments of the draft document. This document selectively presents the results of these discussions. This document summarizes recommendations for the clinical and imaging work-up of pancreatic and biliary tract lesions along with indications for cytologic study of these lesions. Prebrushing and FNA requirements are also discussed., (Copyright © 2014 Wiley Periodicals, Inc.)

Purpose: To evaluate, in a phase 2 study, the safety and efficacy of induction gemcitabine, oxaliplatin, and cetuximab followed by selective capecitabine-based chemoradiation in patients with borderline resectable or unresectable locally advanced pancreatic cancer (BRPC or LAPC, respectively)., Methods and Materials: Patients received gemcitabine and oxaliplatin chemotherapy repeated every 14 days for 6 cycles, combined with weekly cetuximab. Patients were then restaged; "downstaged" patients with resectable disease underwent attempted resection. Remaining patients were treated with chemoradiation consisting of intensity modulated radiation therapy (54 Gy) and concurrent capecitabine; patients with borderline resectable disease or better at restaging underwent attempted resection., Results: A total of 39 patients were enrolled, of whom 37 were evaluable. Protocol treatment was generally well tolerated. Median follow-up for all patients was 11.9 months. Overall, 29.7% of patients underwent R0 surgical resection (69.2% of patients with BRPC; 8.3% of patients with LAPC). Overall 6-month progression-free survival (PFS) was 62%, and median PFS was 10.4 months. Median overall survival (OS) was 11.8 months. In patients with LAPC, median OS was 9.3 months; in patients with BRPC, median OS was 24.1 months. In the group of patients who underwent R0 resection (all of which were R0 resections), median survival had not yet been reached at the time of analysis., Conclusions: This regimen was well tolerated in patients with BRPC or LAPC, and almost one-third of patients underwent R0 resection. Although OS for the entire cohort was comparable to that in historical controls, PFS and OS in patients with BRPC and/or who underwent R0 resection was markedly improved., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: Patients with several painful functional gastrointestinal disorders (FGIDs) are reported to have a high prevalence of psychosocial disturbance. These aspects have not been studied extensively in patients with suspected Sphincter of Oddi dysfunction (SOD)., Methods: A total of 214 patients with post-cholecystectomy pain and suspected SOD were enrolled in seven US centers in a multicenter-randomized trial (Evaluating Predictors and Interventions in Sphincter of Oddi Dysfunction). Baseline assessments included pain descriptors and burden, structured psychosocial assessments of anxiety/depression, coping, trauma, and health-related quality of life. Patients with high levels of depression, suicidal ideation, or psychosis were excluded., Results: The study population (92% female, mean age 38) reported anxiety (9%), depression (8%), past sexual trauma (18%), and physical abuse (10%). Of the total screened population (n=1460), 3.9% of the patients were excluded because of the presence of defined severe psychological problems. The mean medical outcomes study short-form-36 (SF-36) physical and mental composite scores were 38.70 (s.d.=7.89) and 48.74 (s.d.=9.60), respectively. Most subjects reported symptoms of other FGIDs. There were no correlations between the extent of the pain burden in the 3 months before enrollment and the baseline anxiety scores or victimization history. However, those with greater pain burden were significantly more depressed. There were no meaningful differences in the psychosocial parameters in subjects with or without irritable bowel, and those who had cholecystectomy for stones or functional gallbladder disease. Those declining randomization were comparable to those randomized., Conclusions: Psychosocial comorbidity in SOD is high. However, it does not appear to differ significantly from that reported in surveys of age- and gender-matched general populations, and may be lower than reported with other FGIDs.

The need for standardized language is increasingly obvious, also within gastrointestinal endoscopy. A systematic approach to the description of endoscopic findings is vital for the development of a universal language, but systematic also means structured, and structure is inherently a challenge when presented as an alternative to the normal spoken word. The efforts leading to the "Minimal Standard Terminology" (MST) of gastrointestinal endoscopy offer a standardized model for description of endoscopic findings. With a combination of lesion descriptors and descriptor attributes, this system gives guidance to appropriate descriptions of lesions and also has a normative effect on endoscopists in training. The endoscopic report includes a number of items not related to findings per se, but to other aspects of the procedure, formal, technical, and medical. While the MST sought to formulate minimal lists for some of these aspects (e.g. indications), they are not all well suited for the inherent structure of the MST, and many are missing. Thus, the present paper offers a recommended standardization also of the administrative, technical, and other "peri-endoscopic" elements of the endoscopic report; important also are the numerous quality assurance initiatives presently emerging. Finally, the image documentation of endoscopic findings is becoming more obvious-and accessible. Thus, recommendations for normal procedures as well as for focal and diffuse pathology are presented. The recommendations are "minimal," meaning that expansions and subcategories will likely be needed in most centers. Still, with a stronger common grounds, communication within endoscopy will still benefit., (© 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

Background: Success in deep biliary cannulation via native ampullae of Vater is an accepted measure of competence in ERCP training and practice, yet prior studies focused on predicting adverse events alone, rather than success. Our aim is to determine factors associated with deep biliary cannulation success, with/ without precut sphincterotomy., Methods: The ERCP Quality Network is a unique prospective database of over 10,000 procedures by over 80 endoscopists over several countries. After data cleaning, and eliminating previously stented or cut papillae, two multilevel fixed effect multivariate models were used to control for clustering within physicians, to predict biliary cannulation success, with and without allowing "precut" to assist an initially failed cannulation., Results: 13018 ERCPs were performed by 85 endoscopists (March 2007 - May 2011). Conventional (without precut) and overall cannulation rates were 89.8% and 95.6%, respectively. Precut was performed in 876 (6.7%). Conventional success was more likely in outpatients (OR 1.21), but less likely in complex contexts (OR 0.59), sicker patients (ASA grade (II, III/V: OR 0.81, 0.77)), teaching cases (OR 0.53), and certain indications (strictures, active pancreatitis). Overall cannulation success (some precut-assisted) was more likely with higher volume endoscopists (> 239/year: OR 2.79), more efficient fluoroscopy practices (OR 1.72), and lower with moderate (versus deeper) sedation (OR 0.67)., Conclusion: Biliary cannulation success appears influenced by both patient and practitioner factors. Patient- and case-specific factors have greater impact on conventional (precut-free) cannulation success, but volume influences ultimate success; both may be used to select appropriate cases and can help guide credentialing policies.

Endoscopy plays an important role in both the diagnosis and the initial management of recurrent acute pancreatitis, as well as the investigation of refractory disease, but it has known limitations and risks. Sound selective use of these therapies, complemented with other lines of investigation such as genetic testing, can dramatically improve frequency of attacks and associated quality of life. Whether endoscopic therapy can reduce progression to chronic pancreatitis, or reduce the risk of malignancy, is debatable, and remains to be proven., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Pain is common and multifactorial among patients with chronic pancreatitis. Underrecognized and undertreated psychosocial comorbidity can exacerbate pain experience. Excess inpatient service utilization within this patient population prompted a performance improvement initiative at a large academic medical center., Methods: An interprofessional treatment approach with programmatic medical, surgical, and psychological and psychiatric interventions was rolled-out in January 2007 and length of stay (LOS) was measured on a quarterly basis for a 2-year period. Trends in resource utilization (LOS, estimated opportunity costs) were assessed with a novel modified bootstrapping technique, Simulation Modeling Analysis (SMA)., Results: From January 1, 2007, through December 31, 2008, SMA revealed a linear downward trend in LOS (ρ = -0.857, p = .0170), and the interprofessional treatment approach was associated with estimated opportunity cost savings of $670,750.27. There were no associated changes in 7-, 14-, and 30-day readmission rates, p > .05., Conclusion: Interprofessional care that combines behavioral approaches to pain management; behavioral contingency management for opioid medication management; psychological and psychotropic treatments for depression, anxiety, and addiction in addition to standard medical and surgical treatments for pancreatitis appears to be associated with lower healthcare costs. Future research should examine patient reported outcomes of this model., (© 2013 National Association for Healthcare Quality.)

Objectives: We aimed to establish benchmarks for fluoroscopy time (FT) in endoscopic retrograde cholangiopancreatography (ERCP) and assess the effect of physician practice networking on time trends., Methods: Data from the ERCP Quality Network were used to assess practice variability in FT and establish case- and provider-level benchmarks of the first 200 cases for providers entering more than 100 cases. Trends in FT and high FT, by 50-patient groupings, were assessed by multilevel multivariate linear and logistic regression models., Results: Median FT was 2.9 minutes, averaging 16% of procedure time. Ninetieth percentiles for the 57 eligible providers were 10 minutes and 22% (n = 9, 185 ERCP). Every 50 cases entered was associated with lower FT. In multivariate analysis, more cases entered, higher lifetime and annual volumes, lower difficulty grade, and manometry had lower FTs; academics, trainee involvement, various therapeutics, and failed cannulation had higher FTs., Conclusions: FT is highly variable, and many provider and case factors predict FT. FT benchmarks are now available. Self-review of one's case FT might decrease FT.

There is increasing interest in the quality of endoscopic practice and in documenting it. Endoscopic retrograde cholangiopancreatography (ERCP) is the most complex and risky procedure performed regularly by gastroenterologists. The goal was to test the acceptability and functioning of a voluntary system for individual endoscopists to report details of their ERCP cases and to compare them with unidentified peers. Participants were compared by site of practice, procedure complexity, volumes, durations, and selected technical success rates. There was no independent audit. A total of 63 endoscopists in the United States entered data on 18 182 procedures over 3 years. Results in academic and community practices were similar, but there were significant and expected differences in the complexity of practice and key quality metrics between endoscopists performing more than and fewer than 100 cases per year. The study provided useful data on variations in ERCP practice in the United States and will assist in planning the development of national projects in this field.

Background: Total pancreatectomy with islet autotransplantation (TP-IAT) is safe and effective in the management of intractable pain associated with chronic pancreatitis (CP). Prevention of pancreatogenic diabetes after TP-IAT is related to islet yield from the diseased pancreas. The purpose of this study is to compare islet yield and insulin requirement in the 76 patients who underwent different surgical procedures before TP-IAT at the Medical University of South Carolina between 2009 and 2011., Methods: Patients were grouped into four categories based on the operation they had before TP-IAT: transduodenal sphincteroplasty/no prior surgery (n=50), Whipple or Beger procedure (n=14), distal pancreatectomy (n=8), or lateral pancreaticojejunostomy (n=4). Islets were harvested from pancreases of those patients at our current good manufacturing practice facility. Total unpurified islets were transplanted into patients via portal vein infusion. Pancreatic fibrosis, islet yield, cell viability, and insulin requirement were measured., Results: The pancreases of transduodenal sphincteroplasty/no prior surgery and Whipple or Beger procedure patients were less fibrotic and had higher islet yield compared with those who had distal pancreatectomy or lateral pancreaticojejunostomy. Higher islet yield also correlated with a greater diabetes-free rate and a lesser insulin requirement at the following intervals: preoperative, postoperative, and 6 months after TP-IAT., Conclusions: Prior surgery is strongly correlated with the extent of pancreatic fibrosis, islet yield, and insulin requirements in CP patients undergoing TP-IAT. The history of prior pancreatic resection and drainage procedures may be used to predict postoperative islet function and help to determine the optimal timing for TP-IAT in CP patients.

Objectives: Patients' memories of personal polyp characteristics have been shown to be inadequate when compared with the medical record. An accurate polyp history is necessary to adhere to guidelines. We sought to determine whether systematically informing patients of the results of their colonoscopy and pathology in a multifaceted manner could increase their knowledge of their personal polyp history., Methods: We conducted a prospective pilot study of 240 consecutive patients undergoing screening colonoscopy with polypectomy by a single endoscopist (B.J.H.) at a tertiary care center. All of the patients were provided with a verbal report of findings immediately after the procedure, an endoscopy report specifying polyp size and number, and a mailed letter specifying the pathology results of their polyps. Telephone contact was attempted for all of the patients. Patients were asked to recall the size, number, and histology of their polyps., Results: One hundred (42%) of the patients completed the telephone survey. Forty patients remembered the polyp number; five remembered their polyp histology, and one recalled the polyp size. None of the patients recalled all three factors, although patients who recalled telling a family member the results of the colonoscopy were more likely to recall at least one polyp descriptor (relative risk 2.62 [95% confidence interval 1.01-6.83]). No other variables were associated with polyp recall., Conclusions: Patients' knowledge of personal polyp characteristics, even after systematic notification, does not seem adequate for determining the best guideline-based colonoscopy surveillance interval. Discussing results with family members may help.

Objectives: The objective of this study was to define the quality of life (QOL) in patients with chronic pancreatitis (CP)., Methods: We studied 443 well-phenotyped CP subjects and 611 control subjects prospectively enrolled from 20 US centers between 2000 and 2006 in the North American Pancreatitis Study 2. Responses to the SF-12 questionnaire were used to calculate the mental (MCS) and physical component summary scores (PCS) with norm-based scoring (normal ≥50). Quality of life in CP subjects was compared with control subjects after controlling for demographic factors, drinking history, smoking, and medical conditions. Quality of life in CP was also compared with known scores for several chronic conditions., Results: Both PCS (38 [SD, 11.5] vs 52 [SD, 9.4]) and MCS (44 [SD, 11.5] vs 51 [SD, 9.2]) were significantly lower in CP compared with control subjects (P < 0.001). On multivariable analyses, compared with control subjects, a profound decrease in physical QOL (PCS 12.02 points lower) and a clinically significant decrease in mental QOL (MCS 4.24 points lower) was seen due to CP. Quality of life in CP was similar to (heart, kidney, liver, lung disease) or worse than (nonskin cancers, diabetes mellitus, hypertension, rheumatoid arthritis) other chronic conditions., Conclusions: The impact of CP on QOL appears substantial. The QOL in CP subjects appears to be worse or similar to the QOL of many other chronic conditions.

Objectives: A recent large-scale randomized controlled trial (RCT) demonstrated that rectal indomethacin administration is effective in addition to pancreatic stent placement (PSP) for preventing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in high-risk cases. We performed a post hoc analysis of this RCT to explore whether rectal indomethacin can replace PSP in the prevention of PEP and to estimate the potential cost savings of such an approach., Methods: We retrospectively classified RCT subjects into four prevention groups: (1) no prophylaxis, (2) PSP alone, (3) rectal indomethacin alone, and (4) the combination of PSP and indomethacin. Multivariable logistic regression was used to adjust for imbalances in the prevalence of risk factors for PEP between the groups. Based on these adjusted PEP rates, we conducted an economic analysis comparing the costs associated with PEP prevention strategies employing rectal indomethacin alone, PSP alone, or the combination of both., Results: After adjusting for risk using two different logistic regression models, rectal indomethacin alone appeared to be more effective for preventing PEP than no prophylaxis, PSP alone, and the combination of indomethacin and PSP. Economic analysis revealed that indomethacin alone was a cost-saving strategy in 96% of Monte Carlo trials. A prevention strategy employing rectal indomethacin alone could save approximately $150 million annually in the United States compared with a strategy of PSP alone, and $85 million compared with a strategy of indomethacin and PSP., Conclusions: This hypothesis-generating study suggests that prophylactic rectal indomethacin could replace PSP in patients undergoing high-risk ERCP, potentially improving clinical outcomes and reducing healthcare costs. A RCT comparing rectal indomethacin alone vs. indomethacin plus PSP is needed.

Background: International guidelines for the management of nonvariceal upper gastrointestinal bleeding have not been widely adopted in clinical practice. We sought to determine whether a national, multifaceted intervention could improve adherence to guidelines, especially for patients at high risk of nonvariceal upper gastrointestinal bleeding., Methods: In this randomized trial, we stratified hospitals by region and size and allocated sites to either the control or experimental group. Health care workers in the experimental group were given published guidelines, generic algorithms, stratification scoring systems and written reminders and attended multidisciplinary guideline education groups and case-based workshops. These interventions were implemented over a 12-month period after randomization, with performance feedback and benchmarking. The primary outcome of adherence rates to key guidelines in endoscopic and pharmacologic management, determined by chart review, was adjusted according to site characteristics and possible within-site dependencies. We also report the rates of adherence to other recommendations., Results: Forty-three sites were randomized to the experimental (n=21) or control (n=22) groups. In our primary analysis, we compared patients before (experimental group: n=402 patients; control group: n=424 patients) and after (experimental group: n=361 patients; control group: n=389 patients) intervention. Patient-level analysis revealed no significant difference in adherence rates to the guidelines after the intervention (experimental group: 9.8%; control group: 4.8%; p=0.99) after adjustment for the rate of adherence before the intervention (experimental group: 13.2%; control group: 7.1%). The adherence rates to other guidelines were similar and decreased over time, varying between 5% and 93%., Interpretation: This national knowledge translation-based trial suggests poor adherence to guidelines on nonvariceal upper gastrointestinal bleeding. Adherence was not improved by an educational intervention, which highlights both the complexity and poor predictability of attempting to alter the behaviour of health care providers (Trial registration: ClinicalTrials.gov, no. MCT-88113).

Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR and SPINK1 variants were associated with pancreatitis risk. We now report two associations at genome-wide significance identified and replicated at PRSS1-PRSS2 (P < 1 × 10(-12)) and X-linked CLDN2 (P < 1 × 10(-21)) through a two-stage genome-wide study (stage 1: 676 cases and 4,507 controls; stage 2: 910 cases and 4,170 controls). The PRSS1 variant likely affects disease susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous (or hemizygous in males) CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men (male hemizygote frequency is 0.26, whereas female homozygote frequency is 0.07).

Background: Hemoglobin A1c (HbA1c) is a reliable marker for long-term glycemic control in obese diabetic patients. Roux-en-Y gastric bypass improves HbA1c levels over time. However, it is not clear whether the preoperative HbA1c level is a predictor of the outcome in these patients. Our objectives were to understand the predictive capacity of the preoperative HbA1c level in gastric bypass patients at a single university-based Bariatric Center of Excellence., Methods: We performed a retrospective review of 468 charts from 2006 to 2009 of patients who had undergone Roux-en-Y gastric bypass. Using their preoperative HbA1c status, the patients were categorized and the postoperative outcomes compared., Results: Of the 468 patients reviewed, 310 (66.2%) had a HbA1c of <6.5% (group 1), 92 (19.4%) had a HbA1c of 6.5-7.9% (group 2), and 66 (14.1%) had a HbA1c level of >8.0% (group 3). No difference was found among the 3 groups in baseline body mass index, race, procedure type, length of stay, hospital cost, and smoking status. Groups 2 and 3 were associated with older age, male gender, and higher baseline creatinine. Groups 2 and 3 also had a proportionally greater inpatient postoperative blood glucose level. An elevated postoperative glucose level was independently associated with wound infection (P = .008) and acute renal failure (P = .04). Also, group 3 experienced worse outcomes, including less weight loss at 18 months and fewer diabetic remissions. Over time, however, the vast majority in all groups achieved excellent chronic glycemic control, with HbA1c <6.5% after Roux-en-Y gastric bypass., Conclusion: Poor preoperative glycemic control is associated with worse glucose level control postoperatively, fewer diabetic remissions, and less weight loss. An elevated mean postoperative glucose level is independently associated with increased morbidity., (Copyright © 2012 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Routine second-look endoscopy in modern-era peptic ulcer bleeding (PUB) remains controversial., Objective: To assess the effectiveness of routine second-look endoscopy in patients with PUB exhibiting high-risk stigmata after standard medical care and endoscopic therapy., Design: Comprehensive literature searches (1990-2011) were performed, seeking randomized trials comparing a routine with an as-needed second endoscopy., Main Outcome Measurements: The main outcome was rebleeding. Secondary outcomes were surgery and mortality. Subanalyses assessed the influence of study quality, rebleeding definitions, endoscopic hemostasis modality, and proton pump inhibitor (PPI) therapies. Analyses were performed with Revman 5.1. Results are shown as odds ratios (ORs) and 95% confidence intervals (CIs)., Results: Only 4 published articles completely reporting studies and 4 abstracts (of 577 citations) were included (938 patients). Rebleeding was significantly decreased by a routine second-look endoscopy (OR 0.55; 95% CI, 0.37-0.81), as was surgery (OR 0.43; 95% CI, 0.19-0.96), but not mortality (OR 0.65; 95% CI, 0.26-1.62). Results remained robust with varying definitions of rebleeding, but not with varying endoscopic hemostasis modalities and PPI therapies; the only trial in which high-dose PPI was used did not show a benefit of a second-look endoscopy. When removing the 2 trials that included patients at highest risk of rebleeding, no significant benefit attributable to a second-look endoscopy was noted (OR 0.65; 95% CI, 0.42-1.00)., Limitations: The small number of trials and patients in each of these studies., Conclusions: In the absence of high-dose PPI, especially in patients at very high risk (eg, active bleeding), routine second-look endoscopy appears effective in these selected patients with PUB. However, the generalizability of these results to the era of high-dose PPI and otherwise unselected patients with high-risk stigmata is unclear., (Copyright © 2012 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Objective: The Endoscopic retrograde cholangiopancreatography (ERCP) Quality Network is a voluntary system for submission of data to generate individual report cards and benchmarking. The aim of this study was to compare aspects of ERCP practice between USA and UK participants., Design: Analysis was limited to USA and UK based endoscopists who had each entered more than 30 cases. A number of practice and performance measures were studied including, rates of deep biliary cannulation, sedation use and success in bile duct stone removal., Setting and Patients: Patients attending for routine and emergency ERCP in participating tertiary and secondary care units in the UK and USA., Results: 61 US endoscopists performed 18 182 procedures and 16 UK endoscopists 3172, respectively. The UK participants performed less complex procedures as judged by the accepted complexity grading system, 8% versus 35% at grade 3, p<0.001. There was a significantly greater use of sedation as opposed to anaesthesia in the UK 97% versus 34%, p<0.001. UK deep biliary cannulation rate was 93% versus 97%, p<0.001. For small bile duct stones (<10 mm) the UK success rate was 96% compared with 99%, p<0.001., Conclusion: The present data, while not purporting to be an accurate representation of practice in either country, documents good technical success in both cohorts, albeit significantly better in the USA. The inexorable drive to greater accountability and transparency of outcomes in endoscopic practice is likely to lead to increased participation in subsequent benchmarking projects., Competing Interests: Competing interests: PBC and JR have undertaken consultancy work for the Olympus Corporation of America.

Background: Preliminary research suggests that rectally administered nonsteroidal antiinflammatory drugs may reduce the incidence of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP)., Methods: In this multicenter, randomized, placebo-controlled, double-blind clinical trial, we assigned patients at elevated risk for post-ERCP pancreatitis to receive a single dose of rectal indomethacin or placebo immediately after ERCP. Patients were determined to be at high risk on the basis of validated patient- and procedure-related risk factors. The primary outcome was post-ERCP pancreatitis, which was defined as new upper abdominal pain, an elevation in pancreatic enzymes to at least three times the upper limit of the normal range 24 hours after the procedure, and hospitalization for at least 2 nights., Results: A total of 602 patients were enrolled and completed follow-up. The majority of patients (82%) had a clinical suspicion of sphincter of Oddi dysfunction. Post-ERCP pancreatitis developed in 27 of 295 patients (9.2%) in the indomethacin group and in 52 of 307 patients (16.9%) in the placebo group (P=0.005). Moderate-to-severe pancreatitis developed in 13 patients (4.4%) in the indomethacin group and in 27 patients (8.8%) in the placebo group (P=0.03)., Conclusions: Among patients at high risk for post-ERCP pancreatitis, rectal indomethacin significantly reduced the incidence of the condition. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00820612.).

Background: In 2008, the American College of Gastroenterology (ACG) modified its colorectal screening guidelines regarding patients with family histories of colorectal polyps, specifically highlighting the importance of obtaining detailed history that includes the number, type, and size of adenomas found in a patient's relative. This information is then used to guide screening recommendations for these patients., Objective: To assess the proportion of patients undergoing screening colonscopy for a family history of polyps who have knowledge of their family members' colonoscopy findings., Design: Retrospective, single-center cohort pilot study., Setting: Tertiary care medical center., Patients: Patients who presented for screening colonoscopy between 2008 and 2010 with an indication of family history of polyps., Interventions: Obtain detailed history regarding patient's family history of polyps, including which family member, age of family member at diagnosis, size, type and number of polyps found., Main Outcome Measurements: Knowledge of family history., Results: Seventy-three patients were included in the study. Their knowledge of their family histories of polyps showed the following: 23.2% (17/73; 95% CI, 14%-35%) did not know which family member had polyps, 42.5% (31/73; 95% CI, 31%-55%) did not know the age at diagnosis, 71.2% (52/73; 95% CI, 59%-81%) did not know the polyp type, 90.4% (66/73; 95% CI, 81%-96%) did not know the number of polyps found, and 97.3% (71/73; 95% CI, 90%-100%) did not know the polyp size., Limitations: Retrospective study at a single tertiary referral center., Conclusions: Patients' knowledge regarding the details of their family histories of polyp data appears often unknown or incomplete. Thus, at present, it may not appear feasible or practical to incorporate this level of information in colon cancer screening guidelines., (Copyright © 2012 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Background: Emerging evidence shows that transcranial direct current stimulation (tDCS), a minimally invasive brain stimulation technique, has analgesic effects in chronic pain patients and in healthy volunteers with experimental pain. No studies have examined the analgesic effects of tDCS immediately after surgical/endoscopic procedures. Endoscopy investigating abdominal pain, especially ERCP, can cause significant postprocedural pain., Objective: To test the feasibility, efficacy, and safety of tDCS on post-ERCP pain and analgesia use., Design: Randomized, sham-controlled, pilot study., Setting: Tertiary-care medical center., Patients: This study involved 21 patients who were hospitalized overnight for ERCP for unexplained right upper quadrant pain., Intervention: Twenty minutes of real 2.0 mA tDCS or sham (anode over left prefrontal cortex; cathode over gut-representation of right sensory cortex) immediately after ERCP., Main Outcome Measurements: Pain (visual analogue scale, McGill pain questionnaire, brief pain inventory), patient-controlled analgesia use, adverse events., Results: Real tDCS was associated with 22% less total hydromorphone use, versus sham. The slope of the cumulative patient-controlled analgesia usage curve was significantly steeper in the sham tDCS group (F [2,13] = 15.96; P = .0003). Real tDCS patients reported significantly less pain interference with sleep (t [17] = 3.70; P = .002) and less throbbing pain (t [16] = 2.37; P = .03). Visual analogue scale pain and mood scores (4 hours post-ERCP) suggested a nonsignificant advantage for real tDCS, despite less hydromorphone use. Side effects of tDCS were limited to mild, self-limited tingling, itching, and stinging under electrodes., Limitations: Small sample size, variability in chronic pain, and chronic opioid use., Conclusion: In this pilot study, tDCS appears to be safe, has minimal side effects, and may reduce postprocedural analgesia requirements and subjective pain ratings. Future studies appear warranted., (Copyright © 2011 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Background: Working parties of the American Society for Gastrointestinal Endoscopy (ASGE) Quality Committee recently published a proposed new lexicon for adverse events and a separate extensive review of risk factors. The complexity of procedures also affects outcomes., Objective: To establish a system for grading the complexity of endoscopic procedures., Design: Voting on levels 1 (easiest) to 4 (most difficult) on a list of possible procedures and contexts., Setting: Community and academic gastroenterologists in the United States, Canada, and Britain., Main Outcome Measurements: Median scores of votes cast., Results: Consensus list of levels 1 through 4 contexts and procedures., Limitations: Eminence rather than evidence based., Conclusions: A consensus list was developed for comments and testing to complement the proposed lexicons for adverse events and risk factors., (Copyright © 2011 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Background: The Rosemont criteria (RC) were recently proposed by expert consensus to standardize endoscopic ultrasound (EUS) features and thresholds for diagnosing chronic pancreatitis (CP); however, they are cumbersome and are not validated., Objective: To determine interobserver agreement between RC and conventional criteria (CC), and to assess intertest agreement in the diagnosis of CP., Methods: Thirty-six consecutive patients who underwent EUS for abdominal pain or pancreatitis were retrospectively reviewed. Anonymized images were independently chosen as best representations of the pancreatic body and reviewed by three experts who recorded the presence of CC and RC features. Agreement (proportion and kappa statistic) between CC and RC was calculated. Interobserver agreement within the CC and RC was assessed. Secondary comparisons with endoscopic retrograde cholangiopancreatography were made where available., Results: Using CC, 60 readings (83.3%) were negative for CP, while 12 readings (16.7%) were positive. Using RC, 59 readings (81.9%) were negative for CP, while 13 (18.1%) were positive. The weighted kappa for interobserver agreement for CC (four categories: normal⁄low probability, indeterminate, high probability or calcific) was 0.50, with 80.0% overall agreement, versus 0.27 and 68.1% for the four RC categories (normal, indeterminate, suggestive of and consistent with). Agreement on a positive diagnosis with CC was 86.1% (P=0.38 [McNemar's exact test]), with a kappa of 0.47; for RC, agreement was lower at 80.6% (P=0.016 [McNemar's exact test]), with a kappa of 0.38. For patients who underwent endoscopic retrograde cholangiopancreatography (n=12), false-negative and false-positive rates between CC and RC did not appear to be different., Conclusions: The RC do not appear to achieve the goals of improving accuracy and interobserver agreement for diagnosing CP.