Pathogenesis

The cause of SOD is not well understood. It is categorized as a benign, acalculous obstructive disorder at the level of the SO. There are several proposed causes. One is the formation of a stenosis at the ampulla from passage of a gallstone or gravel over an extended time period. A second possibility is attributed to SO hypertension either caused by a congenital hypertrophic sphincter or an overly responsive smooth muscle contraction of the sphincter to neuronal or hormonal stimuli.

Epidemiology

The prevalence of SOD is difficult to ascertain given that the diagnosis is one of exclusion and based on a high level of suspicion, often after response to a biliary and/or pancreatic sphincterotomy. Up to 1.5% of the US population report symptoms consistent with SOD based on survey data, with a 3-fold female predilection. It is estimated that 10% to 20% of patients who undergo cholecystectomy have subsequent recurrent or residual upper abdominal pain; these patients may have SOD. Estimates for pancreatic SOD are limited to small cohort studies with 33% to 40% of idiopathic recurrent pancreatitis suspected to be from SOD.

Classification of Sphincter of Oddi

There have been several reported classification schemes of SOD in an effort to objectify the diagnosis. The most widely adopted is the Milwaukee classification scheme proposed by Hogan and Geenen. In this scheme, SOD is classified into biliary types I, II, and III based on upper abdominal symptoms, biochemical abnormalities, and radiographic results ( Table 1 ). Subsequently, this classification was broadened to include patients with pancreatic-type pain and relapsing pancreatitis (by single-center expert opinion but never validated in randomized controlled trials [RCTs]). Type I is characterized by (1) dilated CBD or main pancreatic ducts, with some variations in the cutoffs in what is considered a dilated duct (note that the classification fails to consider the degree of bile dilation before and after cholecystectomy); (2) greater than a 1.5- to 2.0-fold elevation in liver-associated enzymes (aminotransferases or alkaline phosphatase levels) or pancreatic enzymes (amylase or lipase) on at least 2 occasions during episodes of pain; and (3) typical, episodic biliary, or pancreatic pain. Type II is suspected when 2 of the 3 aforementioned criteria are present. Finally, type III has been defined by intense biliary or pancreatic-type pain alone with no evidence of laboratory or radiographic abnormalities during episodes of pain or at baseline.

Despite these criteria, some remain skeptical of the diagnosis, contending that type I is rather a consequence of chronic gravel or sludge passage with subsequent papillary stenosis, type II a result of stone passage without stenosis, and type III a functional disorder often associated with gastroparesis, irritable bowel syndrome, nonulcer dyspepsia, and sphincter spasm. Indeed, recent evidence from a multicenter RCT questions the very validity of the third subtype of SOD. In the Evaluating Predictors and Interventions in Sphincter of Oddi Dysfunction (EPISOD) trial, postcholecystectomy patients with suspected SOD type III had no difference in pain relief following sphincterotomy when compared with those who underwent a sham endoscopic procedure. A similar lack of benefit following sphincterotomy was found in a subset of trial patients who had presumed SOD type II with demonstrated liver test abnormalities. These data point to a lack of therapeutic benefit from sphincter obliteration in this subpopulation, a maneuver that should resolve SO hypertension or spasm and raises many questions about the diagnosis of type III and perhaps even type II disease. Such findings are substantial given that half of the patients who have pain following gallbladder removal may have SOD types I or II, and a large number were presumed to have SOD type III.

Clinical Features

A common presentation for patients suspected to have SOD is disabling, intermittent , or episodic pain in the epigastric or right upper quadrant (RUQ) in a middle-aged woman. However, the disease is not sex or age definitive. The diagnosis is typically made following cholecystectomy as it is difficult, if not impossible, to diagnose SOD in patients with an intact gallbladder. Biliary SOD can present as episodic, postprandial RUQ pain with or without cholestasis similar to that experienced with choledocholithiasis. Pancreatic SOD generally results in more prolonged pain, radiating to the back, and can be associated with pancreatitis. Conversely, chronic, unrelenting epigastric or RUQ pain is not caused by SOD. Physical examination is typically nonspecific for abdominal pain, though an astute practitioner may elicit musculoskeletal pain or a succession splash suggestive of gastroparesis as an alternative diagnosis.

Given the ambiguity in the clinical presentation of patients with SOD, additional screening tools can be helpful to guide one’s practice and prompt further testing. The Rome III criteria system is a symptom-based, diagnostic tool developed to aid the classification of functional gastrointestinal disorders when symptoms are not explained by the presence of a structural or tissue abnormality. The most recent criteria, revised in 2006, encompass both biliary and pancreatic SOD with a description of characteristic pain symptoms ( Box 1 ). The diagnosis of functional biliary or pancreatic pain, presumably from SOD, is supported with or without evidence of transient enzyme elevations.

Diagnostic Testing

Patients with SOD are at the highest risk of developing post-ERCP pancreatitis with a prevalence as high as 25%. Therefore, care must be taken to avoid unnecessary invasive testing to establish a diagnosis. Equally important, if not more so, is to ensure that a diagnosis of occult malignancy is not missed in patients with ductal dilation and abnormal pancreatic or liver function tests. Less invasive imaging to assess ductal dilation, by endoscopic ultrasound, transabdominal ultrasound, helical computed tomography, or magnetic resonance cholangiopancreatography (MRCP), should be used. Provocation with intravenous cholecystokinin or secretin can augment the detection of a dilated bile or pancreatic duct in the setting of sphincter stenosis when coupled with one of the aforementioned noninvasive modalities. Other transit studies, the most crude of which is assessment for delayed biliary emptying following a cholangiogram with intraprocedural positional changes, are no longer routinely performed. Recent investigation using serial MRCP following morphine-neostigmine (Prostigmin) stimulation (Nardi provocation test, originally done with transabdominal ultrasound) has been associated with provocative results to include pronounced secretion of pancreatic juice and may someday play a role in the diagnosis of SOD. Hepatobiliary scintigraphy (HIDA) can be used to evaluate underlying gallbladder disease and demonstrate partial biliary obstruction as evident in SOD with prompt hepatic uptake and biliary secretion but poor ductal clearance. However, HIDA can be equivocal if not misleading for biliary dyskinesia depending on patient nutritional and medication intake (ie, narcotic use) preceding the study. Variation in radiologist infusion technique can also lead to highly inaccurate HIDA results, although scintigraphic scores have been proposed as an alternative noninvasive test of choice.

SOM is considered the gold standard for SOD investigation. Expert consensus at a National Institutes of Health conference previously recommended that patients with suspected SOD, particularly types II and III, be referred for manometry rather than diagnostic ERCP alone. High basal sphincter pressures can be confirmatory of a presumptive diagnosis of SOD. However, the performance characteristics have been lackluster. Patients can have fluctuating measurements throughout the day, and pressure readings can be similar for both symptomatic and normal patients. Furthermore, SOM has proven to be unreliable as a predictor of response to sphincterotomy, especially for type III disease. Even postsphincterotomy patients can have abnormally high manometric readings, questioning its reliability as a diagnostic test for SOD. Patient demographics, pancreaticobiliary enzyme levels, presence of gallbladder disease, pain patterns, use of narcotics, underlying functional disorders, and psychological comorbidities have not been found to correlate with manometric results. Several other limitations of SOM preclude its universal use on all patients with suspected SOD, including (1) need for center expertise and challenging manometry catheter placement; (2) variation in pressure measurements from different types of catheter equipment, variable sphincter lumen size, probe position, and point in time when a spasm is captured; and (3) undue risk involved in catheter insertion during diagnostic ERCP. Measurement of liver enzymes and biliary dilation may be sufficient, if not superior, to manometry for diagnosis and predicting response to therapy. The latter strategy seems cost-effective when factoring in the patients and endoscopists’ time, center resources, and potential hospitalization risks incurred with diagnostic SOM; yet, to date, there are no cost analysis studies that validate this claim.