Biliary sphincterotomy for sphincter of Oddi disorder: is sphincterotomy cutting it?

Sphincter of Oddi disorders (SOD) are characterized by periodic abdominal pain similar to biliary and/or pancreatic origin pain, with or without a dilated biliary tree and abnormal liver chemistries, in patients who have already undergone cholecystectomy (1). The disease pathophysiology, diagnosis and management options have remained controversial and continued to evolve over the past five decades. Initially, SOD was thought to result from abnormal sphincter function, resulting in increased resistance to bile flow and increased intra-biliary pressure (2). Attributing abdominal pain to sphincter hypertension required endoscopic demonstration of abnormal sphincter pressures and resolution of pain following sphincterotomy. However, studies have failed to consistently demonstrate a correlation of abdominal pain with increased sphincter pressures and pain relief with sphincter ablation, leading to the acceptance of nociceptive sensitization and cross-sensitization to other visceral stimuli as a more widely accepted explanation (1).

Understanding of the “syndrome” of SOD has always been based on the presence or absence of objective, physician-defined criteria, including dilation of the biliary tree and/or elevation of liver chemistries for “biliary type SOD”, and dilation of pancreatic duct and elevation of pancreatic enzymes or imaging of acute pancreatitis for “pancreatic type SOD”. Those with both criteria were considered SOD I, those with either criterion SOD II and those with neither were referred to as SOD III—biliary or pancreatic, or both. The majority of patients with SOD I were thought to have ampullary stenosis, and biliary sphincterotomy has been recommended (3). Suggested management of patients with SOD II (re-named as suspected functional biliary sphincter disorder) has remained variable. Suspected SOD I and II SOD have often undergone endoscopic retrograde cholangiopancreatography (ERCP) with biliary sphincterotomy in community practices, with high risk of potentially severe complications, especially pancreatitis as well as perforation, resulting in unpredictable outcomes (4). In contrast to SOD I and II, which seem to make sense as there are objective abnormalities suggesting biliary and/or pancreatic duct obstruction, SOD III has always remained controversial, with the majority of endoscopists not “believing” in this entity. Historically, SOD III had been approached as a viable entity only at tertiary centers with a special interest, frequently utilizing sphincter of Oddi manometry, generally to determine whether to perform biliary or dual sphincterotomy (5,6). Figure 1 demonstrates the independent ampullary, biliary and pancreatic sphincters comprising the sphincter of Oddi in the ampulla.

Figure 1 Schematic diagram showing ampullary, biliary and pancreatic sphincters comprising the sphincter of Oddi in the ampulla.

To address the controversial syndrome of SOD III, the Evaluating Predictors and Interventions in Sphincter of Oddi Dysfunction (EPISOD) trial was conducted over nearly a decade and involved the majority of tertiary centers that specialize in SOD (7). The study found no benefit of sphincterotomy over sham, whether biliary alone or biliary and pancreatic, determined by manometric findings. As expected, there were a significant number of complications, some severe. As a result of these findings in the EPISOD trial, not only has SOD III been abandoned, but virtually no centers consider ERCP for patients with abdominal pain syndromes. In addition, the practice of sphincter of Oddi manometry has almost completely stopped (8).

We read with great interest the article titled “Sphincterotomy for biliary sphincter of Oddi disorder and idiopathic acute recurrent pancreatitis: the RESPOnD longitudinal cohort” published by Coté et al. in the journal Gut (9). Authors conducted a prospective cohort study to measure the 12-month response to ERCP with sphincterotomy in suspected SOD patients at 14 US medical centers. Patient-reported outcome measures with a focus on quality of life outcomes were assessed, with primary outcomes involving Patient Global Impression of Change (PGIC) scores and secondary outcomes including change in pain-related disability as well as physical and mental health scores. The efforts are commendable, and we laud the authors for conducting a balanced prospective study with well-defined outcomes. The majority of the patients (89%) had objective criteria, thus consisting of suspected SOD I/II or pancreatic SOD, leaving only the remaining 10.8% with suspected SOD III. Nearly 20% of patients had metabolic dysfunction-associated steatotic liver disease (MASLD), which itself can lead to abnormal liver chemistries and a significant proportion (63%) of the included cohort carried functional diagnoses such as irritable bowel syndrome, fibromyalgia or gastroparesis, with nearly half meeting criteria for somatization disorder. This confounded the specificity of clinical presentation of SOD, and expectantly, there was no association between history of MASLD, irritable bowel syndrome (IBS) or gastroparesis and response to ERCP in this study. Only 0.9% underwent sphincter of Oddi manometry in this trial, similar to a recent real-world large database study (8). We believe this to be a strength rather than a weakness, as this allows application of the results to standard practice.

Overall, the response rate to sphincterotomy was 57.4% with a significant number of these patients (73%) reporting their symptoms as much improved or very much improved through the PGIC questionnaire at 12 months. Most interestingly, physician described characteristics (bile duct size, elevated transaminases or patient characteristics) were not associated with a response to sphincterotomy. There was no difference in response rates across SOD subtypes (I–III, pancreatic or mixed), suggesting “objective criteria” for SOD, although widely believed to lend validity to offering ERCP and sphincterotomy, had limited utility. Of note, the initial Milwaukee classification of SOD incorporated objective criteria including bile duct size and elevated transaminases (10), however, these criteria were not “truly objective”. Over the decades, subsequent studies found imperfect associations between bile duct size, confounded by age, post-cholecystectomy reservoir effect, and progressive dilation secondary to narcotics (11,12). Furthermore, steatotic liver disease, be it metabolic or alcoholic, are frequent etiologies of mild to moderate transaminase elevation in this population.

Patients meeting primary outcomes had significantly higher physical health summary scores (6.0 vs. 2.8, P=0.029) and mental health summary scores (7.6 vs. 3.2, P=0.014) than those who did not. Patients without somatization disorder, with normal baseline physical and mental health, and not requiring opiates to manage baseline pain had response rates >70%. Authors note that this population is most likely to respond to ERCP. The EPISOD trial demonstrated that response rate to sphincterotomy for SOD III was similar to sham cohort and ever since, the utilization of biliary and pancreatic sphincterotomy has significantly and consistently downtrended, while incidence rates of SOD continued to increase (8). This downtrend in sphincterotomy was not associated with an increase in prescribed pharmaceutical therapy (tricyclics, nifedipine, or nitrates) for suspected SOD.

Results of the Results of the ERCP for SPhincter of Oddi Disorders (RESPOnD) trial revives the idea of sphincterotomy for SOD (9), though caution must be exercised during patient selection. Nearly two decades ago, it was demonstrated that patient clinical characteristics rather than duct size and abnormal biochemistry are associated with favorable outcomes post-biliary and/or pancreatic sphincterotomy (13). Patients with daily narcotic use, delayed gastric emptying, age <40 years and normal pancreatic manometry were associated with unfavorable long-term outcomes after biliary with or without pancreatic sphincterotomy (13). Though none of those patient characteristics were significantly associated with response to sphincterotomy in the current trial, recent opioid use, low baseline physical health and somatization disorder were important factors, providing signals for characteristics associated with non-response in real world cohort.

While potentially practice changing, some limitations of the trial cannot be ignored. The study enrolled consecutive patients with suspected SOD without randomization, thus, introducing the possibility of selection bias. The overall response rates across SOD types hovered around 55%, however, without a sham group, the true response attributed to sphincterotomy cannot be determined. Previously, in the EPISOD trial, placebo effect was attributed to the 37% of patients that had relief of abdominal pain in the sham group (7). Placebo response is a genuine psychological response with contribution to patient well-being; however, performing ERCP for possible placebo response cannot be justified. Despite technical expertise at large volume centers in the RESPOnD study, serious AE occurred in approximately 32% of patients.

Of all indications for ERCP, the risk of adverse events, especially pancreatitis, is highest when the procedure is performed for suspected SOD (4). Post-ERCP pancreatitis was noted in 10.3% in the RESPOnD study. Although rectal non-steroidal anti-inflammatory drugs have been shown to independently reduce risk of post ERCP pancreatitis, placement of small caliber pancreatic stents has been repeatedly shown to be the most effective, and critical, for safety of ERCP in this setting, and to add additional protection to non-steroidal anti-inflammatory drugs (NSAIDs) alone (14). Surprisingly, data on prophylactic indomethacin or protective pancreatic stent placement were not reported in the RESPOnD study.

In summary, the RESPOnD trial revives the rationale for biliary sphincterotomy for SOD, which has been on decline since the EPISOD study. Biliary sphincterotomy offers hope for SOD patients. However, careful patient selection, weighing the risk of significant adverse events against the benefit of possible relief of pain, and exemplary technique, including utilization of all available strategies for reduction of post ERCP pancreatitis including reliable and atraumatic placement of protective pancreatic stents, remains critical prior to offering sphincterotomy to SOD patients.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, HepatoBiliary Surgery and Nutrition. The article has undergone external peer review.

Peer Review File: Available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-2025-493/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-2025-493/coif). S.K.A. reports serving as a consultant for Boston Scientific, Cook Medical, Steris, Merit Medical, and Micro-Tech, and as an advisor for Olympus and Provation. The other author has no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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