Endoscopic sphincterotomy for adults with biliary sphincter of Oddi dysfunction.

Background: The sphincter of Oddi comprises a muscular complex encircling the distal part of the common bile duct and the pancreatic duct regulating the outflow from these ducts. Sphincter of Oddi dysfunction refers to the abnormal opening and closing of the muscular valve, which impairs the circulation of bile and pancreatic juices.

Objectives: To evaluate the benefits and harms of any type of endoscopic sphincterotomy compared with a placebo drug, sham operation, or any pharmaceutical treatment, administered orally or endoscopically, alone or in combination, or a different type of endoscopic sphincterotomy in adults with biliary sphincter of Oddi dysfunction.

Search Methods: We used extensive Cochrane search methods. The latest search date was 16 May 2023.

Selection Criteria: We included randomised clinical trials assessing any type of endoscopic sphincterotomy versus placebo drug, sham operation, or any pharmaceutical treatment, alone or in combination, or a different type of endoscopic sphincterotomy in adults diagnosed with sphincter of Oddi dysfunction, irrespective of year, language of publication, format, or outcomes reported.

Data Collection And Analysis: We used standard Cochrane methods and Review Manager to prepare the review. Our primary outcomes were: proportion of participants without successful treatment; proportion of participants with one or more serious adverse events; and health-related quality of life. Our secondary outcomes were: all-cause mortality; proportion of participants with one or more non-serious adverse events; length of hospital stay; and proportion of participants without improvement in liver function tests. We used the outcome data at the longest follow-up and the random-effects model for our primary analyses. We assessed the risk of bias of the included trials using RoB 2 and the certainty of evidence using GRADE. We planned to present the results of time-to-event outcomes as hazard ratios (HR). We presented dichotomous outcomes as risk ratios (RR) and continuous outcomes as mean difference (MD) with their 95% confidence intervals (CI).

Main Results: We included four randomised clinical trials, including 433 participants. Trials were published between 1989 and 2015. The trial participants had sphincter of Oddi dysfunction. Two trials were conducted in the USA, one in Australia, and one in Japan. One was a multicentre trial conducted in seven US centres, and the remaining three were single-centre trials. One trial used a two-stage randomisation, resulting in two comparisons. The number of participants in the four trials ranged from 47 to 214 (median 86), with a median age of 45 years, and the mean proportion of males was 49%. The follow-up duration ranged from one year to four years after the end of treatment. All trials assessed one or more outcomes of interest to our review. The trials provided data for the comparisons and outcomes below, in conformity with our review protocol. The certainty of evidence for all the outcomes was very low. Endoscopic sphincterotomy versus sham Endoscopic sphincterotomy versus sham may have little to no effect on treatment success (RR 1.05, 95% CI 0.66 to 1.66; 3 trials, 340 participants; follow-up range 1 to 4 years); serious adverse events (RR 0.71, 95% CI 0.34 to 1.46; 1 trial, 214 participants; follow-up 1 year), health-related quality of life (Physical scale) (MD -1.00, 95% CI -3.84 to 1.84; 1 trial, 214 participants; follow-up 1 year), health-related quality of life (Mental scale) (MD -1.00, 95% CI -4.16 to 2.16; 1 trial, 214 participants; follow-up 1 year), and no improvement in liver function test (RR 0.89, 95% CI 0.35 to 2.26; 1 trial, 47 participants; follow-up 1 year), but the evidence is very uncertain. Endoscopic sphincterotomy versus endoscopic papillary balloon dilation Endoscopic sphincterotomy versus endoscopic papillary balloon dilationmay have little to no effect on serious adverse events (RR 0.34, 95% CI 0.04 to 3.15; 1 trial, 91 participants; follow-up 1 year), but the evidence is very uncertain. Endoscopic sphincterotomy versus dual endoscopic sphincterotomy Endoscopic sphincterotomy versus dual endoscopic sphincterotomy may have little to no effect on treatment success (RR 0.65, 95% CI 0.32 to 1.31; 1 trial, 99 participants; follow-up 1 year), but the evidence is very uncertain. Funding One trial did not provide any information on sponsorship; one trial was funded by a foundation (the National Institutes of Diabetes and Digestive and Kidney Diseases, NIDDK), and two trials seemed to be funded by the local health institutes or universities where the investigators worked. We did not identify any ongoing randomised clinical trials.

Authors' Conclusions: Based on very low-certainty evidence from the trials included in this review, we do not know if endoscopic sphincterotomy versus sham or versus dual endoscopic sphincterotomy increases, reduces, or makes no difference to the number of people with treatment success; if endoscopic sphincterotomy versus sham or versus endoscopic papillary balloon dilation increases, reduces, or makes no difference to serious adverse events; or if endoscopic sphincterotomy versus sham improves, worsens, or makes no difference to health-related quality of life and liver function tests in adults with biliary sphincter of Oddi dysfunction. Evidence on the effect of endoscopic sphincterotomy compared with sham, endoscopic papillary balloon dilation,or dual endoscopic sphincterotomyon all-cause mortality, non-serious adverse events, and length of hospital stay is lacking. We found no trials comparing endoscopic sphincterotomy versus a placebo drug or versus any other pharmaceutical treatment, alone or in combination. All four trials were underpowered and lacked trial data on clinically important outcomes. We lack randomised clinical trials assessing clinically and patient-relevant outcomes to demonstrate the effects of endoscopic sphincterotomy in adults with biliary sphincter of Oddi dysfunction.