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.

Contemporary Outcomes of Transduodenal Sphincteroplasty: the Importance of Surgical Quality.

BACKGROUND: Sphincter of Oddi dysfunction (SOD) is managed primarily by endoscopic sphincterotomy (ES); however, surgical transduodenal sphincteroplasty (TDS) is a treatment option for select patients. In our high-volume pancreatico-biliary practice, we have observed variable outcomes among TDS patients; therefore, we sought to determine preoperative predictors of durable improvement in quality of life. METHODS: SOD patients treated by TDS between January 2006 and December 2015 were studied. The primary outcome measure was long-term changes in quality of life after sphincteroplasty. The secondary outcome measure examined postoperative outcomes, including postoperative complications, need for repeat procedures, and readmission rates. Perioperative data were abstracted, and the SF-36 quality-of-life (QoL) survey was administered. Standard statistical analysis included non-parametric methods to examine bivariate associations. RESULTS: Eighty-eight patients had an average follow-up duration of 6.7 (± 2.9) years. Thirty (34%) patients were naïve to endoscopic therapy. Patients with prior endoscopy averaged 2.1 procedures (range 1 to 13) prior to surgery. Perioperative morbidity was 27%; one postoperative death was caused by severe acute pancreatitis. Twenty-nine (33%) patients required subsequent biliary-pancreatic procedures. QoL analysis from available patients showed that 66% were improved or much improved. With multivariable analysis including SOD type and prior endoscopic instrumentation, freedom from surgical complication was the only variable that correlated significantly with a good outcome (p < 0.02). CONCLUSION: Surgical transduodenal sphincteroplasty provides durable symptom management for select patients with sphincter of Oddi dysfunction. Minimizing surgical complications optimizes long-term outcomes.

The efficacy and safety of endoscopic sphincterotomy in patients with Sphincter of Oddi dysfunction: a systematic review and meta-analysis.

OBJECTIVE: Sphincter of Oddi dysfunction (SOD) has been used to describe patients with RUQ abdominal pain without an etiology. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of ES (endoscopic sphincterotomy) for SOD. METHODS: The study methodology follows the PRISMA guidelines. A comprehensive search was conducted using MEDLINE and EMBASE databases for RCTs with ES in patients with SOD. The primary outcome assessed was the improvement of abdominal pain after ES/sham. A random effects model was used to calculate pooled estimates for each outcome of interest. RESULTS: Of the initial 55 studies, 23 were screened and thoroughly reviewed. The final analysis included 3 studies. 340 patients (89.7% women) with SOD were included. All patients had a cholecystectomy. Most included patients had SOD type II and III. The pooled rate of technical success of ERCP was 100%. The average clinical success rate was 50%. The pooled cumulative rate of overall AEs related to all ERCP procedures was 14.6%. In the sensitivity analysis, only one study significantly affected the outcome or the heterogeneity. CONCLUSION: ES appears no better than placebo in patients with SOD type III. Sphincterotomy could be considered in patients with SOD type II and elevated SO basal pressure.

Transduodenal Sphincteroplasty: A Visual Case Study.

BACKGROUND: Sphincter of Oddi dysfunction is a challenging and rare clinical entity resulting in pancreatobiliary pain and stasis of bile and pancreatic juice. This problem was classically treated with surgical therapy, but as classification of the disease has changed and newer methods of endoscopic evaluation and therapy have evolved, operative transduodenal sphincteroplasty is now generally reserved as a final therapeutic option for these patients. In this video and manuscript, we describe our approach to operative transduodenal sphincteroplasty in a patient with type I Sphincter of Oddi dysfunction. METHODS: A 50-year-old female with history of Roux-en-Y gastric bypass presented with episodic right-upper-quadrant and epigastric abdominal pain with associated documented elevations in liver chemistries. Preoperative cross-sectional imaging demonstrated dilation of her common bile duct. After multidisciplinary discussion, the decision was made to pursue operative transduodenal sphincteroplasty. RESULTS: All key operative steps of the transduodenal sphincteroplasty are demonstrated in the embedded video. Key operative steps include laparotomy, generous Kocher maneuver, and duodenotomy over the ampulla, allowing access for sequential biliary and pancreatic sphincterotomies and sphincteroplasties with absorbable suture. The duodenotomy and abdominal fascia are then closed. Our patient underwent sequential diet advancement and was discharged to home on postoperative day five. At clinic follow-up, pancreatobiliary-type pain had resolved. CONCLUSION: The embedded video demonstrates a case of operative transduodenal sphincteroplasty, which can provide durable results in appropriate patient populations.

The Next EPISOD: Trends in Utilization of Endoscopic Sphincterotomy for Sphincter of Oddi Dysfunction from 2010-2019.

BACKGROUND & AIMS: For years, the endoscopic management of the disorder formerly known as Type III Sphincter of Oddi Dysfunction (SOD) had been controversial. In 2013, the results of the Evaluating Predictors and Interventions in Sphincter of Oddi Dysfunction (EPISOD) trial demonstrated that there was no benefit associated with endoscopic sphincterotomy for patients with Type III SOD. We aimed to assess the utilization of endoscopic sphincterotomy for patients with SOD in a large population database from 2010-2019. METHODS: We searched a large electronic health record (EHR)-based dataset incorporating over 300 individual hospitals in the United States (Explorys, IBM Watson health, Armonk, NY). Using Systematized Nomenclature of Medicine Clinical Terms (SNOMED-CT) we identified patients with a first-ever diagnosis of "disorder of Sphincter of Oddi" annually from 2010-2019. Subclassification of SOD types was not feasible using SNOMED-CT codes. Stratified by year, we identified the proportion of patients with newly-diagnosed SOD undergoing endoscopic sphincterotomy and those receiving newly-prescribed medical therapy. RESULTS: A total of 39,950,800 individual patients were active in the database with 7,750 index diagnoses of SOD during the study period. The incidence rates of SOD increased from 2.4 to 12.8 per 100,000 persons from 2010-2019 (P < .001). In parallel, there were reductions in the rates of biliary (34.3% to 24.5%) and pancreatic sphincterotomy (25% to 16.4%), respectively (P < .001). Sphincter of Oddi manometry (SOM) was infrequently utilized, <20 times in any given year, throughout the study duration. There were no significant increases in new prescriptions for TCAs, nifedipine, or vasodilatory nitrates. CONCLUSIONS: Among a wide range of practice settings which do not utilize routine SOM, a sudden and sustained decrease in rates of endoscopic sphincterotomy for newly-diagnosed SOD was observed beginning in 2013. These findings highlight the critical importance of high-quality, multi-center, randomized controlled trials in endoscopy to drive evidence-based changes in real-world clinical practice.

Spiral enteroscopy-assisted ERCP in bariatric-length Roux-en-Y anatomy: a large single-center series and review of the literature (with video).

BACKGROUND: Deep enteroscopy-assisted ERCP (DEA-ERCP) in post-bariatric Roux-en-Y (RY) anatomy is challenging. Laparoscopy-assisted ERCP (LA-ERCP) and EUS-directed transgastric ERCP (EDGE) are technically easier and faster but are more invasive and morbid procedures. Therefore, we have used DEA-ERCP as our first-line approach, reserving EDGE and LA-ERCP for cases in which adjunctive techniques that cannot be performed through an enteroscope are required (eg, EUS-FNA, sleeve sphincter of Oddi manometry), or DEA-ERCP failures. The 2 main methods for DEA-ERCP are balloon- and spirus-assisted. Current literature on spiral enteroscopy ERCP (SE-ERCP) in bariatric RY anatomy is scant with low success rates reported. Our center has nearly exclusively used SE-ERCP for bariatric patients. Here, we report one of the largest such series to date. METHODS: This is a retrospective cohort study of consecutive patients with bariatric-length RY anatomy who had SE-ERCP from December 2009 to October 2016 at a tertiary care center, by one operator (S.N.S.). Primary outcomes included success at reaching the papilla, cannulation success, success of desired therapeutic intervention, and overall SE-ERCP success. RESULTS: Thirty-five SE-ERCPs were performed (28 in bariatric RY gastric bypass and 7 other long-limb RY surgical reconstructions). The papilla was reached in 86% (30/35) of cases. Cannulation success in patients in whom deep cannulation was indicated (28/30) was 100% (28/28 cases, including the 24 cases with native papilla). Therapeutic ERCP success was 100% (28/28). Overall SE-ERCP success was 86% (30/35). Median length of stay was 3 days. Median procedure time was 189 minutes. Reasons for SE-ERCP failures included RY anastomosis stricture, adhesions (2), long Roux limb, and redundant small bowel. Two of these patients underwent interventional radiology-guided percutaneous biliary drainage, 2 patients had laparoscopy-assisted ERCP, and 1 patient had EUS-guided antegrade cholangioscopy with sphincteroplasty and stone clearance. There were no adverse events. CONCLUSION: With sufficient allotted time (median procedure time ∼3 hours) and high operator experience (a single-operator volume that exceeds that of other published series), SE-ERCP is safe and effective in bariatric, long-limb RY patients with an overall success rate of 86%, which is higher than previously reported.

The EPISOD study: long-term outcomes.

BACKGROUND AND AIMS: The EPISOD (Evaluating Predictors and Interventions in Sphincter of Oddi Dysfunction) study randomized patients with post-cholecystectomy pain, and little or no objective evidence for biliary obstruction, to sphincterotomy or sham intervention. Results at 1 year showed no benefit for the active treatment. We now report the outcomes at up to 5 years. METHODS: One hundred three patients completing 1 year, and still blinded to treatment allocation, were enrolled and followed by phone every 6 months for a median of 58 months (range, 17-71 months). Their success was assessed at the final visit by 2 criteria: (1) a low pain score (Recurrent Abdominal Pain and Disability instrument [RAPID] <6) and (2) much or very much improved on the Patients' Global Impression of Change (PGIC) questionnaire (both with no repeat intervention and not taking narcotics). RESULTS: By the RAPID criteria, success rates for the patients in the sphincterotomy and sham arms were similar: 26/65 (40%) versus 16/38 (42%), respectively. However, by the PGIC criteria, actively treated patients fared worse: 16/43 (37%) versus 16/22 (73%). A total of 75 patients underwent active treatment during the entire study. Their success rate by the RAPID criteria was 31 (41%) compared with 16 (62%) who had no active treatment at any time. CONCLUSIONS: These data confirm our initial report that endoscopic sphincterotomy is no better than sham intervention in these patients (and, by some criteria, worse), and that ERCP can no longer be recommended. The patients have genuine and often severe symptoms, and further research is needed to establish effective management. (Clinical trial registration number: 00688662 05/3/2008.).

Risk factors of post- endoscopic retrograde cholangiopancreatography pancreatitis in biliary type sphincter of Oddi dysfunction in Japanese patients.

OBJECTIVE: Suspected sphincter of Oddi dysfunction (SOD) is a well-known risk factor for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). The indication of ERCP for suspected SOD patients was very low in Japan compared to other countries. Therefore, the risk of PEP may be different in Japanese SOD patients. The objective of this study was to evaluate the risk of PEP in suspected biliary type SOD in Japan. METHODS: From December 1996 to January 2017, 72 patients were suspected as having biliary type SOD, by questionnaire, liver function tests, hepatobiliary scintigraphy, abdominal ultrasonography, upper gastrointestinal endoscopy, endoscopic ultrasonography and magnetic resonance cholangiopancreatography. Finally, 60 patients who underwent ERCP were included in this study, and the factors associated with PEP were evaluated. RESULTS: The overall PEP rate was 23.3% (n = 14). Diagnostic ERCP alone for SOD did not increase the risk of PEP. The correlation of PEP incidence with pancreatic duct guidewire (PGW) technique and endoscopic sphincterotomy (EST) was indicated in univariate and multivariate analysis. Pancreatic stent placement was a risk in univariate analysis but not in multivariate analysis. CONCLUSIONS: PGW technique and EST for biliary type SOD were important risk factors for PEP. Pancreatic stenting was ineffective for prevention of PEP.

Outcomes of Endoscopic Retrograde Cholangiopancreatography (ERCP) and Sphincterotomy for Suspected Sphincter of Oddi Dysfunction (SOD) Post Roux-En-Y Gastric Bypass.

BACKGROUND: Sphincter of Oddi dysfunction (SOD) is thought to be a cause of chronic abdominal pain post Roux-en-Y gastric bypass, and current practice of performing endoscopic retrograde cholangiopancreatography (ERCP) with or without sphincterotomy is not supported by evidence. In addition to the complexity and risks of the procedure in patients with Roux-en-Y anatomy, the outcomes are uncertain and debatable. We performed a retrospective review and analysis of post-gastric bypass patients who had undergone ERCP with sphincterotomy to determine the effectiveness in patients with suspected SOD. METHODS: Over a period of 5 years at the University of Minnesota, we retrospectively reviewed a prospectively collected database of a cohort of patients whom had a previous Roux-en-Y gastric bypass and whom had a subsequent ERCP for suspected SOD. Patients were categorized by modified Milwaukee classification, and outcomes were evaluated by patients' self-reporting of symptoms at follow-up. RESULTS: We identified 50 patients who underwent laparoscopic-assisted gastrostomy for endoscopic retrograde cholangiopancreatography post Roux-en-Y gastric bypass over the study period. Within this group, 35 patients (70%) were suspected to have SOD. Nine patients (25.7%) were classified as type I, 19 patients (54.3%) type II, and seven patients (20%) type III. Thirty-four patients (97.1%) had biliary sphincterotomy, and 17 patients (48.6%) had both biliary and pancreatic sphincterotomy. Fourteen (40%) had repeated ERCP. At median follow-up of 11.5 months, type I SOD had two responders (25%), type II had nine responders (52.9%), and type III had one responder (14.3%). A subgroup analysis did not show significant differences in improvement of symptoms between patients whom had single versus repeated ERCP or biliary sphincterotomy alone versus both biliary and pancreatic sphincterotomy. Three patients (9%) had post-ERCP pancreatitis. CONCLUSIONS: SOD in patients post Roux-en-Y gastric bypass is complex due to multiple confounding factors. Rome III and Milwaukee classification systems assist us in the diagnosis and treatment of sphincter dysfunction until we have a better way to predict treatment response post sphincterotomy. Current treatment is based on the type of disorder and anatomy of biliary ducts. Types I and II sphincter dysfunction particularly associated with dilated biliary duct on imaging have the best response to endoscopic sphincterotomy and therefore should be considered taking into account the risks and benefit. Repeated sphincterotomy and concurrent pancreatic sphincterotomy is generally not useful.

Post-cholecystectomy syndrome and sphincter of Oddi dysfunction: past, present and future.

INTRODUCTION: Post-cholecystectomy syndrome and the concept of a causal relationship to sphincter of Oddi dysfunction, despite the controversy, has presented a clinically relevant conflict for decades. Historically surgeons, and now gastroenterologists have expended tremendous efforts towards trying to better understand the dilemma that is confounded by unique patient phenotypes. Areas covered: This review encompasses the literature from a century of experience on the topic of post-cholecystectomy syndrome. Relevant historical and anecdotal experiences are examined in the setting of insights from evaluation of recently available controlled data. Expert commentary: Historical observations and recent data suggest that patients with post-cholecystectomy syndrome can be categorized as follows. Patients with sphincter of Oddi stenosis will most often benefit from treatment with sphincterotomy. Patients with classic biliary pain and some objective evidence of biliary obstruction may have a sphincter of Oddi disorder and should be considered for endoscopic evaluation and therapy. Patients with atypical post-cholecystectomy pain, without any evidence consistent with biliary obstruction, and/or with evidence for another diagnosis or dysfunction should not undergo ERCP.

Early precut is as efficient as pancreatic stent in preventing post-ERCP pancreatitis in high-risk subjects - A randomized study.

BACKGROUND: The most common adverse event of endoscopic retrograde cholangiopancreatography is pancreatitis. Precut sphincterotomy has been regarded as a risk factor. Some authors have stated that early precut may actually reduce post-ERCP pancreatitis risk. However, early precut as a preventive measure has not been compared to other preventive measures, such as pancreatic duct stent placement. AIM: To compare the efficacy of early precut sphincterotomy versus pancreatic duct stent placement in high-risk subjects undergoing endoscopic retrograde cholangiopancreatography for the prevention of post-endoscopic cholangiopancreatography. MATERIALS AND METHODS: This was a single-blinded, randomized trial that took place in two tertiary referral centers in Buenos Aires, from November 2011 to December 2013. ERCP subjects presented at least one of the following risk factors: female sex, age less than 40 years, clinical suspicion of sphincter of Oddi dysfunction, previous pancreatitis, and/or common bile duct diameter of less than 8 mm. Only those who presented a difficult biliary cannulation were randomized into two groups: those who received early precut sphincterotomy and those in whom persistency of biliary cannulation was intended, with subsequent pancreatic duct stent placement after cholangiography was achieved. The incidence of post-ERCP pancreatitis, as well as other adverse events incidence, was compared. RESULTS: Overall, 101 patients were enrolled, 51 in the pancreatic duct stent group and 50 in the early precut group. Pancreatitis rate was similar in both groups (3.92% vs 4%, p NS). In all cases, pancreatitis was classified as mild. There were no deaths registered. CONCLUSION: Early precut was associated with an incidence of adverse events similar to pancreatic duct stent placement.

Advances in endoscopic management of biliary complications after living donor liver transplantation: Comprehensive review of the literature.

Apart from noticeable improvements in surgical techniques and immunosuppressive agents, biliary complications remain the major causes of morbidity and mortality after living donor liver transplantation (LDLT). Bile leakage and stricture are the predominant complications. The reported incidence of biliary complications is 15%-40%, and these are known to occur more frequently in living donors than in deceased donors. Despite the absence of a confirmed therapeutic algorithm, many approaches have been used for treatment, including surgical, endoscopic, and percutaneous transhepatic techniques. In recent years, nonsurgical approaches have largely replaced reoperation. Among these, the endoscopic approach is currently the preferred initial treatment for patients who undergo duct-to-duct biliary reconstruction. Previously, endoscopic management was achieved most optimally through balloon dilatation and single or multiple stents placement. Recently, there have been significant developments in endoscopic devices, such as novel biliary stents, as well as advances in endoscopic technologies, including deep enteroscopy, the rendezvous technique, magnetic compression anastomosis, and direct cholangioscopy. These developments have resulted in almost all patients being managed by the endoscopic approach. Multiple recent publications suggest superior long-term results, with overall success rates ranging from 58% to 75%. This article summarizes the advances in endoscopic management of patients with biliary complications after LDLT.

Sphincter of Oddi Dysfunction.

This article reviews the diagnosis and management of sphincter of Oddi dysfunction (SOD), including the various factors to consider before embarking on endoscopic therapy for SOD. Selection starts with patient education to include possible patient misconceptions related to symptoms caused by the pancreaticobiliary sphincter as well as reinforcing the risks associated with the diagnosis and therapy. The likelihood of relief of recurrent abdominal pain attributed to SOD is related to the classification of SOD type and a crucial consideration before considering endoscopic therapy in light of recent evidence.