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.)

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.

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.

Patients with biliopancreatic-type pain, but without significant abnormalities on imaging and laboratory tests, have been categorized as suspected SOD type III, with the supposition that sphincter dysfunction causes pain. Clinical predictors of manometric SOD are important to avoid unnecessary ERCP, but are lacking. The EPISOD (Evaluating Predictors and Interventions in Sphincter of Oddi Dysfunction) trial is a randomized, sham-controlled study representing the largest prospective cohort of SOD-III.

The role of pancreas divisum in unexplained acute pancreatitis (AP) is controversial. Most data on minor papilla endoscopic sphincterotomy (MPES) come from retrospective series without validated pain outcomes. The FRAMES NIH study aims to examine outcomes after MPES in the largest prospective series to date.

A high prevalence of psychosocial disturbance is associated with many painful functional GI disorders but there are no data for patients with SOD III.

Given risks of diagnostic pancreatography, non-invasive imaging (EUS (endoscopic ultrasound), MRCP (magnetic resonance cholangio-pancreatography)) would be ideal to diagnose pancreas divisum (PDiv) in unexplained pancreatitis. Pre-ERCP knowledge of PDiv can help plan therapy and guide informed consent. Reported accuracies of EUS and MRCP in PDiv have been highly variable. The FRAMES NIH study on outcomes after sphincterotomy in PDiv assessed the positive predictive value (PPV) of imaging in the largest prospective series to date.

The role of pancreas divisum in unexplained acute pancreatitis is controversial. Most data on minor papilla therapy come from case series, most without controls, except 1 small randomized trial of 1-year stenting; most feel the latter is no longer acceptable therapy due to duct damage that occurs with longterm stenting. The FRAMES (Frequency of Recurrent Acute pancreatitis after Minor papilla Endoscopic Sphincterotomy) study is an NIH study in its pilot phase, aiming to examine prospective outcomes and trial feasibility in this group of patients.

Background: Sphincter of Oddi dysfunction (SOD) is a controversial topic, especially in patients with no objective findings on laboratory or imaging studies (SOD type III). The value of ERCP manometry with sphincterotomy is unproven and carries significant risks.Objective: To describe the process of planning and initiating a randomized sham-controlled study to establish whether patients with SOD respond to sphincter ablation, and whether the outcomes are predicted by the pain patterns, presence or absence of other functional GI or psychosocial problems, or the results of manometry.Design: Planning a trial to establish which patients with "suspected SOD" (if any) respond to endoscopic sphincter ablation.Setting: Meetings and correspondence by a planning group of gastroenterologists and clinical research specialists hosted at the Medical University of South Carolina.Patients: Clarifying subject characteristics and inclusion and exclusion criteria.Interventions: Defining the questionnaires, therapies, randomizations, and numbers of subjects required by outcome measures. Defining the metrics of success and failure.Results: The planning resulted in funding for the proposed study as a cooperative agreement with the National Institute of Diabetes and Digestive and Kidney Diseases.Limitations: Lack of data required several consensus decisions in designing the protocol.Conclusion: The planning process was challenging, and some changes were needed after initiation.* (Clinical trial registration number: NCT00688662.) (Gastrointest Endosc 2010;72:986-91.)