Effect of endoscopic sphincterotomy for suspected sphincter of oddi dysfunction on pain-related disability following cholecystectomy

The EPISOD randomized clinical trial

Peter B. Cotton, Valerie Durkalski, Joseph Romagnuolo, Qi Pauls, Evan Fogel, Paul Tarnasky, Giuseppe Aliperti, Martin Freeman, Richard Kozarek, Priya Jamidar, Mel Wilcox, Jose Serrano, Olga Brawman-Mintzer, Grace Elta, Patrick Mauldin, Andre Thornhill, Robert Hawes, April Wood-Williams, Kyle Orrell, Douglas Drossman & 1 others Patricia Robuck

Research output: Contribution to journalArticle

91 Citations (Scopus)

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: 00688662

Original languageEnglish
Pages (from-to)2101-2109
Number of pages9
JournalJournal of the American Medical Association
Volume311
Issue number20
DOIs
StatePublished - 2014

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Sphincter of Oddi Dysfunction
Endoscopic Sphincterotomy
Cholecystectomy
Randomized Controlled Trials
Pain
Endoscopic Retrograde Cholangiopancreatography
Manometry
Pancreatitis
Abdominal Pain
Observational Studies
Therapeutics
Pressure
Narcotics
Random Allocation

ASJC Scopus subject areas

  • Medicine(all)

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Effect of endoscopic sphincterotomy for suspected sphincter of oddi dysfunction on pain-related disability following cholecystectomy : The EPISOD randomized clinical trial. / Cotton, Peter B.; Durkalski, Valerie; Romagnuolo, Joseph; Pauls, Qi; Fogel, Evan; Tarnasky, Paul; Aliperti, Giuseppe; Freeman, Martin; Kozarek, Richard; Jamidar, Priya; Wilcox, Mel; Serrano, Jose; Brawman-Mintzer, Olga; Elta, Grace; Mauldin, Patrick; Thornhill, Andre; Hawes, Robert; Wood-Williams, April; Orrell, Kyle; Drossman, Douglas; Robuck, Patricia.

In: Journal of the American Medical Association, Vol. 311, No. 20, 2014, p. 2101-2109.

Research output: Contribution to journalArticle

Cotton, PB, Durkalski, V, Romagnuolo, J, Pauls, Q, Fogel, E, Tarnasky, P, Aliperti, G, Freeman, M, Kozarek, R, Jamidar, P, Wilcox, M, Serrano, J, Brawman-Mintzer, O, Elta, G, Mauldin, P, Thornhill, A, Hawes, R, Wood-Williams, A, Orrell, K, Drossman, D & Robuck, P 2014, 'Effect of endoscopic sphincterotomy for suspected sphincter of oddi dysfunction on pain-related disability following cholecystectomy: The EPISOD randomized clinical trial', Journal of the American Medical Association, vol. 311, no. 20, pp. 2101-2109. https://doi.org/10.1001/jama.2014.5220
Cotton, Peter B. ; Durkalski, Valerie ; Romagnuolo, Joseph ; Pauls, Qi ; Fogel, Evan ; Tarnasky, Paul ; Aliperti, Giuseppe ; Freeman, Martin ; Kozarek, Richard ; Jamidar, Priya ; Wilcox, Mel ; Serrano, Jose ; Brawman-Mintzer, Olga ; Elta, Grace ; Mauldin, Patrick ; Thornhill, Andre ; Hawes, Robert ; Wood-Williams, April ; Orrell, Kyle ; Drossman, Douglas ; Robuck, Patricia. / Effect of endoscopic sphincterotomy for suspected sphincter of oddi dysfunction on pain-related disability following cholecystectomy : The EPISOD randomized clinical trial. In: Journal of the American Medical Association. 2014 ; Vol. 311, No. 20. pp. 2101-2109.
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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: 00688662",
author = "Cotton, {Peter B.} and Valerie Durkalski and Joseph Romagnuolo and Qi Pauls and Evan Fogel and Paul Tarnasky and Giuseppe Aliperti and Martin Freeman and Richard Kozarek and Priya Jamidar and Mel Wilcox and Jose Serrano and Olga Brawman-Mintzer and Grace Elta and Patrick Mauldin and Andre Thornhill and Robert Hawes and April Wood-Williams and Kyle Orrell and Douglas Drossman and Patricia Robuck",
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T1 - Effect of endoscopic sphincterotomy for suspected sphincter of oddi dysfunction on pain-related disability following cholecystectomy

T2 - The EPISOD randomized clinical trial

AU - Cotton, Peter B.

AU - Durkalski, Valerie

AU - Romagnuolo, Joseph

AU - Pauls, Qi

AU - Fogel, Evan

AU - Tarnasky, Paul

AU - Aliperti, Giuseppe

AU - Freeman, Martin

AU - Kozarek, Richard

AU - Jamidar, Priya

AU - Wilcox, Mel

AU - Serrano, Jose

AU - Brawman-Mintzer, Olga

AU - Elta, Grace

AU - Mauldin, Patrick

AU - Thornhill, Andre

AU - Hawes, Robert

AU - Wood-Williams, April

AU - Orrell, Kyle

AU - Drossman, Douglas

AU - Robuck, Patricia

PY - 2014

Y1 - 2014

N2 - 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: 00688662

AB - 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: 00688662

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