title: Effect of endoscopic sphincterotomy for suspected sphincter of Oddi dysfunction on pain-related disability following cholecystectomy: the EPISOD randomized clinical trial.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00688662.
authors.affiliation: Medical University of South Carolina, Charleston.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Cotton
authors.affiliation: Medical University of South Carolina, Charleston.
authors.forename: Valerie
authors.initials: V
authors.lastname: Durkalski
authors.affiliation: Medical University of South Carolina, Charleston.
authors.forename: Joseph
authors.initials: J
authors.lastname: Romagnuolo
authors.affiliation: Medical University of South Carolina, Charleston.
authors.forename: Qi
authors.initials: Q
authors.lastname: Pauls
authors.affiliation: Indiana University, Indianapolis.
authors.forename: Evan
authors.initials: E
authors.lastname: Fogel
authors.affiliation: Dallas Medical Center, Dallas, Texas.
authors.forename: Paul
authors.initials: P
authors.lastname: Tarnasky
authors.affiliation: Midwest Therapeutic Endoscopy Consultants, St Louis, Missouri.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Aliperti
authors.affiliation: University of Minnesota Medical School, Minneapolis.
authors.forename: Martin
authors.initials: M
authors.lastname: Freeman
authors.affiliation: Virginia Mason Medical Center, Seattle, Washington.
authors.forename: Richard
authors.initials: R
authors.lastname: Kozarek
authors.affiliation: Yale University, New Haven, Connecticut.
authors.forename: Priya
authors.initials: P
authors.lastname: Jamidar
authors.affiliation: University of Alabama, Birmingham.
authors.forename: Mel
authors.initials: M
authors.lastname: Wilcox
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland.
authors.forename: Jose
authors.initials: J
authors.lastname: Serrano
authors.affiliation: Ralph H. Johnson VA Medical Center, Charleston, South Carolina.
authors.forename: Olga
authors.initials: O
authors.lastname: Brawman-Mintzer
authors.affiliation: University of Michigan, Ann Arbor.
authors.forename: Grace
authors.initials: G
authors.lastname: Elta
authors.affiliation: Medical University of South Carolina, Charleston.
authors.forename: Patrick
authors.initials: P
authors.lastname: Mauldin
authors.affiliation: Medical University of South Carolina, Charleston.
authors.forename: Andre
authors.initials: A
authors.lastname: Thornhill
authors.affiliation: Medical University of South Carolina, Charleston12Florida Hospital, Orlando.
authors.forename: Robert
authors.initials: R
authors.lastname: Hawes
authors.affiliation: Medical University of South Carolina, Charleston.
authors.forename: April
authors.initials: A
authors.lastname: Wood-Williams
authors.affiliation: Medical University of South Carolina, Charleston.
authors.forename: Kyle
authors.initials: K
authors.lastname: Orrell
authors.affiliation: University of North Carolina and Drossman Gastroenterology PLLC, Chapel Hill.
authors.forename: Douglas
authors.initials: D
authors.lastname: Drossman
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland.
authors.forename: Patricia
authors.initials: P
authors.lastname: Robuck
mesh_terms: D015746:Abdominal Pain / Q000209:etiology / Q000503:physiopathology*; D000328:Adult; D002760:Cholangiopancreatography, Endoscopic Retrograde / Q000379:methods; D002763:Cholecystectomy / Q000009:adverse effects*; D005260:Female; D006304:Health Status; D006801:Humans; D008297:Male; D008365:Manometry; D008875:Middle Aged; D009294:Narcotics / Q000627:therapeutic use; D010195:Pancreatitis; D046628:Sphincter of Oddi Dysfunction / Q000209:etiology* / Q000601:surgery*; D016717:Sphincterotomy, Endoscopic / Q000009:adverse effects / Q000379:methods*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D009294:Narcotics