Effect of endoscopic sphincterotomy for suspected sphincter of Oddi dysfunction on pain-related disability following cholecystectomy: the EPISOD randomized clinical trial

JAMA. 2014 May;311(20):2101-9. doi: 10.1001/jama.2014.5220.

Abstract

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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Abdominal Pain / etiology
  • Abdominal Pain / physiopathology*
  • Adult
  • Cholangiopancreatography, Endoscopic Retrograde / methods
  • Cholecystectomy / adverse effects*
  • Female
  • Health Status
  • Humans
  • Male
  • Manometry
  • Middle Aged
  • Narcotics / therapeutic use
  • Pancreatitis
  • Sphincter of Oddi Dysfunction / etiology*
  • Sphincter of Oddi Dysfunction / surgery*
  • Sphincterotomy, Endoscopic / adverse effects
  • Sphincterotomy, Endoscopic / methods*
  • Treatment Outcome
  • Young Adult

Substances

  • Narcotics

Associated data

  • ClinicalTrials.gov/NCT00688662