Key messages
– We do not know if endoscopic sphincterotomy compared with sham operation or dual endoscopic sphincterotomy benefits adults with biliary sphincter of Oddi dysfunction, or changes serious or non-serious unwanted effects, quality of life, and liver function.
– We have no data comparing endoscopic sphincterotomy with sham operation, endoscopic papillary balloon dilation,or dual endoscopic sphincterotomyon deaths, non-serious unwanted effects, and hospital stay.
– No trial compared endoscopic sphincterotomy with placebo medicine or another medicine, alone or combined.
– We lack randomised clinical studies assessing relevant outcomes in larger numbers of participants.
What is biliary sphincter of Oddi dysfunction?
The sphincter of Oddi is a muscular valve around the base of the ducts from the gallbladder and pancreas. The valve is usually closed (contracted), but it relaxes when eating to allow bile and pancreatic juices into the small intestine helping digest food.
Biliary sphincter of Oddi dysfunction is a condition where the sphincter cannot contract and relax normally, blocking bile flow and resulting in pain.
How is biliary sphincter of Oddi dysfunction treated?
There are many treatments, including medication, endoscopic sphincterotomy (cutting of the sphincter/muscle of Oddi using an endoscope), or surgery (biliary-enteric drainage).
What is endoscopic sphincterotomy treatment?
Sphincterotomy is a procedure that cuts the sphincter at the end of the bile duct and pancreatic duct to open into the small intestine. Endoscopic means this is done using an endoscope, which is a flexible tube with a camera and light that is inserted from the mouth until it reaches the sphincter. This procedure is used to remove gallstones (small stones containing cholesterol that form in the gallbladder or duct) or any other blockages.
What did we want to find out?
We wanted to know if endoscopic sphincterotomy decreased the number of people with unsuccessful treatment; caused any unwanted effects (for example, death and other serious and non-serious unwanted effects); and had an impact on quality of life, length of hospital stay, and liver function (measured using blood tests to diagnose and monitor liver disease or damage). To do this, we looked for randomised clinical studies that compared endoscopic sphincterotomy versus a placebo medicine (fake medicine with no treatment effect); a sham operation (fake surgical operation); any treatment with medicines, administered by mouth or through the endoscope, alone or in combination; or a different type of endoscopic sphincterotomy. Randomised clinical studies allocate participants to two or more groups, by chance, compare the effects of the treatments (for example, surgical procedure compared with no treatment, a placebo medicine, or with an existing treatment).
What did we do?
We searched medical databases for randomised clinical trials that fulfilled our predefined criteria. We summarised the results and assessed the quality of the evidence.
What did we find?
We found four trials with 433 participants with sphincter of Oddi dysfunction. All trials had limitations in design, conduct, and reporting of outcomes. The largest trial included 214 participants, and the smallest included 47 participants. Two trials were conducted in the USA, one in Australia, and one in Japan. The trials lasted one to four years. One trial included two comparisons. Only one trial explicitly provided information on sponsorship (funded by the National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK)). Two trials seemed to be funded by local health centres or universities where the investigators worked.
The trials compared endoscopic sphincterotomy against sham operation (three trials), endoscopic papillary balloon dilation (an alternative method of endoscopic sphincterotomy that uses a balloon to widen a narrowed part of the sphincter) (one trial), or dual endoscopic sphincterotomy (endoscopic sphincterotomy for biliary and pancreatic sphincters) (one trial). No trials compared endoscopic sphincterotomy against a placebo medicine or any treatment with medicines.
We performed only one meta-analysis (a summary analysis needing data from at least two trials) on the 'number of people with unsuccessful treatment at one to four years after end of treatment', with data from three trials comparing endoscopic sphincterotomy versus sham operation. Because of the small number of randomised participants in the trials, and the small number of trials, we could not reach a conclusion on this outcome. Neither could we reach a conclusion regarding serious unwanted effects because only one trial provided data.
We found inconclusive results for the 'serious unwanted effects' outcome when comparing endoscopic sphincterotomy with endoscopic papillary balloon dilation, and for the 'number of people with unsuccessful treatment at one to four years after end of treatment' outcome when comparing endoscopic sphincterotomy with dual endoscopic sphincterotomy as there was only one trial in each comparison providing data for the two outcomes.
No trials reported death, length of hospital stay, or non-serious unwanted effects.
What are the limitations of the evidence?
We are very uncertain of the results as participants may have known which treatment they received, there were problems with how the trials were run, and there were few trials and data.
How up to date is this evidence?
The evidence is up to date to May 2023.
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.
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.
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.
We used extensive Cochrane search methods. The latest search date was 16 May 2023.
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.
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).
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.