Sphincter of Oddi disorder (SOD) is a syndrome involving recurrent abdominal pain, with or without abnormalities in liver or pancreatic chemistries or duct dilatation. The paucity of controlled data for the treatment of most biliary SOD types and the incomplete response to therapy seen in clinical practice as well as in several trials [1–3], has generated significant controversy as to what the best course of management of these patients is. Consensus opinion holds that patients with biliary SOD type I, presenting with abdominal pain, raised liver function tests, and dilated common bile duct (CBD), should be treated with papillary decompression by means of endoscopic or surgical sphincterotomy [4, 5]. However, the appropriate management of patients with biliary SOD type II and III remains unresolved. Current recommendations, based on two randomized controlled trials, include the use of sphincter of Oddi manometry (SOM) in patients with SOD type II so that sphincterotomy may be performed only in those with elevated pressure [5]. The results of these trials, however, are not in agreement with those of several uncontrolled studies in which outcome was not found to be associated with SOM findings [6–8]. There is no firm evidence as regards to the patients with suspected biliary SOD type III who should be carefully evaluated and treated pharmacologically prior to considering SOM and sphincterotomy [5].

Suspected sphincter of Oddi dysfunction has been shown in several studies to be related to increased complication risk at endoscopic retrograde cholangiopancreatography (ERCP) and SOM/sphincterotomy [9–11]. Thus, the potential benefits should be weighed against this increased complication risk prior to any attempt to treat SOD with endoscopic sphincterotomy.

The aim of the current study was to evaluate the natural history of a series of patients with biliary SOD managed without SOM.

In the current study, we propose that patients with biliary SOD can be managed without SOM. Although it is generally accepted that patients with biliary SOD type I should be treated with biliary sphincterotomy [5, 14], there is some controversy as to the management of biliary type II and III patients. There are only two published randomized controlled trials suggesting that biliary sphincterotomy should be performed in patients with biliary SOD type II or III found to have raised basal biliary Sphincter of Oddi pressure upon SOM [15, 16]. However, one of the trials only included type II patients [15] whilst the other mainly included type II patients with small numbers of type I and III patients [16] rendering their results hard to generalize to all SOD types. Their findings, moreover, are not in line with uncontrolled studies that failed to show any correlation between SOM results and outcome of sphincterotomy [6, 7]. Also, it has been suggested that although abnormally elevated pressure at SOM may predict benefit from biliary sphincterotomy in type II and III patients, the reverse may not hold true [8] and that a single negative SOM study does not rule out sphincter of Oddi dysfunction [17]. Furthermore, Thune et al found that manometric findings compatible with sphincter of Oddi dysfunction, probably due to its episodic nature, are poorly reproducible [18]. A recent study, involving a decision analysis model constructed using a software program, showed that empirical biliary sphincterotomy may be more cost-effective in comparison to a strategy based on the results of manometry for patients with biliary type II pain [19].

In our cohort, a total of 44/59 patients (75%) reported subjective symptomatic benefit after a median follow-up of 15 months. This proportion is similar to that reported in the literature [1–3, 16, 20–22].

The risk of complications, in particular pancreatitis, is of concern in patients with SOD undergoing ERCP/sphincterotomy [9–11]. The occurrence of post-ERCP complications in our study was 18% in general and 16% for post-ERCP pancreatitis in particular, which is comparable to that in previous reports [1, 3, 10, 22]. Having a post-ERCP complication was not found to have any significant effect on symptomatic relief at follow-up. Placement of temporary prophylactic pancreatic duct stents has been suggested to reduce post-ERCP pancreatitis rates in patients with SOD [23, 24]. However, this was not performed in the current study, and thus we cannot exclude the possibility that pancreatic duct stenting might have reduced the incidence of pancreatitis.

There is certain evidence suggesting that the etiology of pain in SOD may be multifactorial. Eighty-five percent of patients continued to have pain at last follow-up with 34% requiring opiate analgesics for pain control (mainly mild opiates). This is in keeping with a previous study in which, despite endoscopic sphincterotomy, 82% of patients with biliary type pain continued to have pain after a mean follow-up of 18 months, indicating that SOD may be a chronic pain disorder with a multifactorial etiology [2]. Duodenal specific visceral hyperalgesia [25] and delayed gastric emptying [3] may be involved in the pathogenesis of pain in these patients. Furthermore, in our cohort 20% of patients experienced at least one recurrence of symptoms after initial response to therapy. Although it has been previously reported that restenosis after endoscopic sphincterotomy for SOD requiring repeated intervention may occur in 13% - 61% during a follow-up of 19 months and 26 months respectively [1, 3], ours is the first study to quantify the proportion of patients with biliary type pain who relapse after combined medical and endoscopic management. Further studies, are warranted to fully elucidate the potential mechanisms of abdominal pain in SOD and the role sphincterotomy may play as a component of a comprehensive pain management.

We did not find any differences in response to therapy between the different subclassifications of SOD. This is in keeping with several studies showing that this classification may be inadequate to predict treatment outcome [2, 3, 20]. It should, however, be noted that a revised version of the initial classification is used nowadays in which noninvasive methods, instead of ERCP, are used to measure CBD diameter and contrast drainage times are no longer utilized [5]. To our knowledge, this revised classification system has not been formally validated.

The presence of an intact gallbladder in our series did not affect symptomatic relief at follow-up. Fifty-six percent of the patients had an intact gallbladder in situ but no gallstones were identified on ultrasound or MRCP/ERCP. Although there are only limited data on SOD and its treatment in patients with gallbladder in situ, SOD is thought to occur in these patients [5]. SOM studies have shown elevated sphincter pressures in a proportion of patients with biliary pain and intact gallbladder [26, 27]. Also, endoscopic sphincterotomy has been shown to be effective in patients with biliary-type pain and gallbladder in situ [26, 27]. However, radionuclide imaging for gallbladder dyskinesia was not performed in our cohort and thus we cannot exclude that some of the patients with an intact gallbladder might have benefited from cholecystectomy.

Certain methodological limitations should be taken into consideration when interpreting the results of the current study. Although consecutive patients were prospectively identified, part of the data analyzed were retrospectively collected from patient files and no validated questionnaire or structured interview was uniformly used to define treatment outcome. However, all patients were treated in a uniform fashion in a single center under the care of a single consultant gastroenterologist (RWC). Furthermore, discharged patients were not contacted to obtain follow-up data post-discharge. Although we would have expected these patients to have been re-referred to our institution in the event of significant change in symptoms we cannot fully exclude the possibility that some discharged patients who relapsed may have been treated elsewhere. Also, the current study was observational. Large prospective interventional trials enrolling patients with SOD of all types are needed in order to study the most appropriate management approach for these patients. Our data, as well as those published by others [2, 3, 20], suggest that SOM results may not necessarily define the management course in such future trials.

In conclusion, patients with biliary sphincter of Oddi disorder may be managed with a combination of endoscopic sphincterotomy (performed in those with dilated common bile duct) and medical therapy without utilization of SOM. The results of this approach with regards to symptomatic relief and ERCP complication rate are comparable to those published in the literature. However, a significant proportion of patients continued to have pain despite subjective symptomatic improvement. Prospective randomized interventional trials enrolling patients with SOD of all types are needed in order to study the most appropriate management approach for these patients.