INTRODUCTION — The sphincter of Oddi (SO) is a muscular structure that encompasses the confluence of the distal common bile duct and the pancreatic duct as they penetrate the wall of the duodenum (figure 1). The term "sphincter of Oddi dysfunction" has been used to describe a clinical syndrome of biliary or pancreatic obstruction related to mechanical or functional abnormalities of the sphincter of Oddi. The terms papillary stenosis, sclerosing papillitis, biliary spasm, biliary dyskinesia, and postcholecystectomy syndrome have been used synonymously.
The treatment of sphincter of Oddi dysfunction (SOD) will be reviewed here. The clinical manifestations and diagnosis of this disorder are discussed separately. (See "Clinical manifestations and diagnosis of sphincter of Oddi dysfunction".)
NATURAL HISTORY — Few studies have addressed the long-term natural history of sphincter of Oddi dysfunction (SOD). The available data suggest that the clinical course is variable depending in part upon the initial biliary classification. (See "Clinical manifestations and diagnosis of sphincter of Oddi dysfunction", section on 'Clinical criteria'.)
In a one-year follow-up study, seven type II patients (biliary pain and either abnormal liver tests or a dilated common bile duct) with abnormal sphincter of Oddi (SO) pressure treated by a sham procedure continued to have symptoms, which resolved only after subsequent sphincterotomy. All patients continued to do well four years later. Five other type II patients with abnormal SO pressure refused sphincterotomy. At four-year follow-up, three were unimproved, while two had "fair" improvement.
The clinical course is unpredictable after a sham or endoscopic sphincterotomy in patients with type III biliary pain (biliary pain but normal liver tests and common bile duct). In one report, 11 such patients were followed for two years after sphincterotomy. Four improved symptomatically while seven had no change. Eleven other patients had a sham procedure, of whom five improved, while six had no change in symptoms during two years of follow-up [1].
TREATMENT GOALS — The goal of treating patients with symptomatic sphincter of Oddi dysfunction (SOD) is to eliminate pain and/or recurrent pancreatitis by improving the impaired flow of biliary and pancreatic secretions into the duodenum, which can be accomplished by pharmacologic, endoscopic, and surgical approaches. Successful treatment depends upon a secure diagnosis. A variety of other disorders, such as irritable bowel syndrome and functional dyspepsia, can cause symptoms that may be confused with SOD. In addition, other causes of pain in patients with postcholecystectomy syndrome or recurrent pancreatitis should be investigated.
PHARMACOLOGIC TREATMENT — Drugs that cause smooth muscle relaxation may be beneficial in patients with sphincter of Oddi dysfunction (SOD). Calcium channel blockers and nitrates have been best studied, although the data are sparse. Although calcium channel blockers and nitrates may have a role in some patients, side effects are common, and, in one series, pharmacologic therapy was ineffective in approximately 50 percent of patients [2]. Thus, in patients at increased risk for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis, we suggest a trial of pharmacologic treatment; however, it is infrequently successful for long-term management.
Calcium channel blockers — Nifedipine reduces basal sphincter of Oddi (SO) pressure in volunteers without SOD, and has a more profound effect in patients with SOD who have elevated basal SO pressure [3,4]. However, results with nifedipine have been conflicting.
The efficacy of nifedipine was evaluated in a placebo-controlled crossover trial that included 28 patients with recurrent biliary pain thought to be related to SOD [4]. Nifedipine (given in the maximal tolerated dose) was associated with significant decreases in a cumulative pain score, number of pain episodes, oral analgesic tablets consumed, and emergency department visits. Responding patients were more likely to have predominant antegrade propagation of phasic contractions on post-treatment SO manometry (SOM), rather than abnormal propagation of phasic contractions. A response to nifedipine could not be predicted by any clinical, radiographic, or manometric criteria.
However, in vivo studies in the Australian brush-tailed possum have shown that calcium channel blockers have greater effects on blood pressure at low doses than they do on sphincter of Oddi motility [5]. A corresponding observation in humans was noted in a placebo-controlled crossover trial involving five patients who were randomly assigned to slow-release nifedipine or placebo during a six-month period [6]. Active treatment was associated with frequent vascular side effects and was no more effective than placebo at controlling symptoms.
Nitrates — Nitrates can produce relaxation of the SO in animal models and in humans [7]. A potential role for nitrates in patients with SOD was suggested by a case report of a patient whose pain disappeared following nitrate administration; pain resolution was associated with a decrease in both basal and phasic SO activity [8]. However, the role of nitrates in the management of SOD has not yet been established by well-designed controlled trials.
Ursodeoxycholic acid — Some studies have implicated biliary microlithiasis in the pathogenesis of postcholecystectomy pain. A randomized, crossover study involving 12 patients found to have microlithiasis (identified from a total of 118 patients with postcholecystectomy pain) reported significant improvement in pain after treatment with ursodeoxycholic acid (300 mg twice daily) compared with untreated controls [9]. Treatment was continued for six months. During a mean of 29 months of follow-up, all patients except one continued to remain free of biliary pain after discontinuing therapy.
This was a single center study involving a small number of patients. The accompanying editorial cautioned about the incorporation of this test into the diagnostic algorithm of postcholecystectomy pain evaluation based upon this study [10]. Additional studies are needed to confirm these findings before a search for biliary microlithiasis can be recommended routinely.
ENDOSCOPIC THERAPY
Endoscopic sphincterotomy — The biliary or pancreatic segment of the sphincter of Oddi can be severed using electrocautery during endoscopic retrograde cholangiopancreatography (ERCP). It should be performed by an experienced, capable endoscopist who has demonstrated good outcomes by sufficient patient follow-up.
Multiple studies have evaluated the benefit of endoscopic sphincterotomy [11-18]. Although the duration of follow-up and inclusion criteria varied, improvement or elimination of pain occurred in approximately 30 to 90 percent of patients. The likelihood of success depends in part upon careful patient selection.
Biliary pain — In patients with biliary pain, biliary sphincterotomy has the greatest benefit for those who have elevated basal sphincter of Oddi (SO) pressures (greater than 40 mmHg). There is general consensus that patients with type I biliary sphincter of Oddi dysfunction (SOD) likely have papillary stenosis and benefit from endoscopic biliary sphincterotomy without the need for preceding SO manometry (SOM). (See "Clinical manifestations and diagnosis of sphincter of Oddi dysfunction", section on 'Clinical criteria'.)
Type II patients generally undergo SOM and those with elevated basal biliary sphincter pressures undergo endoscopic sphincterotomy. Observational studies have not shown a benefit for this approach [13,18-20], but at least two randomized controlled trials support this practice [1,16].
●In one trial, 47 patients thought to have type II biliary SOD based upon clinical findings were included; all the patients were presumed to have biliary pain and had previously undergone cholecystectomy [16]. Before undergoing manometry, the patients were randomly assigned to sphincterotomy or sham sphincterotomy. At one-year follow-up, biliary sphincterotomy improved pain scores and objective parameters in significantly more patients who had elevated basal sphincter pressures compared to those who underwent sham sphincterotomy (90 versus 25 percent, respectively). In contrast, pain scores were similar in patients without elevated pressures, regardless of treatment. Subsequent sphincterotomy benefited the majority of patients with elevated basal pressures who initially underwent sham sphincterotomy.
●A second trial of 81 patients supported the results of the earlier randomized trial [1]. In that trial, the effects of sphincterotomy were evaluated in patients with types I, II, and III biliary SOD. The patients were randomly assigned to endoscopic sphincterotomy or sham sphincterotomy based on a SO biliary manometric pressure measurement. The manometric record was categorized as: (1) normal, (2) stenosis, or (3) dyskinesia.
Twenty-six patients (32 percent) had SO stenosis based on the manometric results. Thirteen of these patients underwent sphincterotomy and thirteen underwent sham sphincterotomy. Patients in the sphincterotomy group showed significantly higher rates of long-term improvement compared to those in the sham group (85 versus 30 percent, respectively). There was no significant difference between patients who underwent sphincterotomy and those who underwent sham sphincterotomy when the manometry was normal or showed dyskinesia.
●In a retrospective study over a period of 20 years, 117 patients with type I SOD underwent ERCP with biliary sphincterotomy [21]. All patients were pain-free at median follow-up of four years.
Other experts advocate performing endoscopic sphincterotomy without prior SOM for type II SOD patients, citing favorable clinical responses and low complication rates [22-25]. However, data are lacking to support this practice.
Among patients with possible type III biliary SOD who continue to have symptoms following cholecystectomy, biliary sphincterotomy is unlikely to lead to symptom improvement. This was examined in a multicenter, randomized, sham-controlled trial (EPISOD study) with 214 patients (141 assigned to sphincterotomy and 73 assigned to a sham procedure) [26]. Using strict criteria, disability due to pain improved in 32 patients who underwent sphincterotomy (23 percent) and in 27 patients who underwent a sham procedure (37 percent; adjusted risk difference -16 percent). There were no subgroups that appeared to benefit from sphincterotomy, including those with abnormal sphincter of Oddi manometry. In addition, ERCP caused pancreatitis in 26 patients (11 percent in the sphincterotomy group and 15 percent in the sham group). This trial suggests that type III biliary SOD may not be a meaningful diagnosis and that functional disorders, such as irritable bowel syndrome, chronic functional abdominal pain, visceral hypersensitivity and, if appropriate, narcotic bowel syndrome, may be better explanations for a patient's symptoms. In a subsequent study that evaluated long-term outcomes in a sub-set of these patients, sphincterotomy and sham arms had similar improvements in pain outcomes but actively treated patients had lower overall patient satisfaction rates [27].
Recurrent pancreatitis — Endoscopic pancreatic sphincterotomy may benefit patients with pancreatitis thought to be due to SOD. In a series of 160 patients with recurrent pancreatitis, endoscopic sphincterotomy resulted in complete and long-lasting resolution of symptoms in 64 percent [28]. However, some patients required repeat sphincterotomy for recurrent SO stenosis.
Pancreatitis is also a potential complication of sphincterotomy. The risk may be greater after pancreatic than after biliary sphincterotomy and most often occurs in patients with pancreatic sphincter hypertension [29]. Placement of a pancreatic stent following biliary sphincterotomy may reduce the incidence of pancreatitis in these patients. (See "Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis" and "Prophylactic pancreatic stents to prevent ERCP-induced pancreatitis: When do you use them?".)
A problem with pancreatic duct stenting is the requirement for another procedure to remove the stent. Nasopancreatic drainage may be an alternative, permitting noninvasive removal of the drain following recovery [28].
Botulinum toxin injection — Endoscopic injection of botulinum toxin for biliary sphincter of Oddi dysfunction has been used successfully by some groups to determine if a symptomatic response might predict a successful outcome to subsequent sphincterotomy [30]. The influence of botulinum toxin on the pancreatic segment of the SO is unknown. Whether this material could be injected successfully into the pancreatic segment without a preceding biliary sphincterotomy is also not known.
SURGERY — Biliary and pancreatic sphincterotomy can also be accomplished by a transduodenal surgical approach. Surgical sphincterotomy has two potential advantages compared to standard endoscopic approaches:
●Surgery allows for greater precision in performing the sphincterotomy. With endoscopic sphincterotomy it is difficult to sever the transampullary septum without risking duodenal perforation. As a result, endoscopic sphincterotomy may not completely relieve pancreatic duct obstruction [31]. Endoscopic sphincterotomy of the biliary segment of the SO also may not affect the pancreatic duct segment at all [32]. These problems are both overcome by performing the sphincterotomy surgically.
●Surgery may reduce the chance of recurrent stenosis due to scarring.
Improvement in biliary pain and recurrent pancreatitis has been demonstrated in approximately 50 to 60 percent of patients treated by surgical sphincterotomy [33-39]. However, surgical sphincterotomy and septoplasty for pancreatitis may be associated with worse outcomes than for recurrent biliary pain [39]. One possible explanation is that some patients have unappreciated pancreatic parenchymal disease that continues to be the source of pain following surgery. For similar reasons, patients with acute recurrent pancreatitis may have better results than those with chronic pancreatitis [37].
Despite these potential advantages, endoscopic therapy is less invasive, has similar outcomes, and is the preferred approach at most centers with experience in this technique.
OTHER APPROACHES
Electroacupuncture — A potential therapeutic role for electroacupuncture was suggested in a pilot study in which an acupoint on the right lateral tibia (GB34) was stimulated, resulting in a significant decrease in basal pressure, amplitude, duration, and frequency of phasic contractions [40]. The inhibition of SO contractility was accompanied by an increase in plasma cholecystokinin (CCK) levels. All changes reverted to baseline upon discontinuation of stimulation. The clinical relevance of these observations remains to be determined.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Biliary infection and obstruction".)
SUMMARY AND RECOMMENDATIONS — The management of sphincter of Oddi dysfunction (SOD) varies depending on whether the patient has type I, II, or III SOD (see "Clinical manifestations and diagnosis of sphincter of Oddi dysfunction"):
●Type I SOD: biliary-type pain, abnormal liver tests, and a dilated common bile duct
●Type II SOD: biliary-type pain and either abnormal liver tests or a dilated common bile duct
●Type III SOD: biliary-type pain but normal liver tests and common bile duct diameter
Endoscopic therapy is preferred for patients with type I SOD, and many patients with type II SOD. Patients with type III SOD are more often managed without endoscopic intervention.
●We suggest that patients with type I SOD be referred directly for endoscopic sphincterotomy, without preprocedure manometry (Grade 2C). (See 'Biliary pain' above.)
●We suggest that patients with type II SOD be referred for sphincter of Oddi manometry and that an endoscopic sphincterotomy be performed if there is evidence of sphincter of Oddi stenosis (Grade 2B). (See 'Biliary pain' above.)
●We suggest that endoscopic sphincterotomy be avoided in patients with type III SOD (Grade 2B). Failure of these patients to respond to biliary sphincterotomy suggests their symptoms may be better explained by a functional disorder. (See 'Biliary pain' above.)
●We suggest patients with recurrent pancreatitis be evaluated for SOD with manometry and that those with elevated sphincter pressures undergo endoscopic sphincterotomy (Grade 2C). (See 'Recurrent pancreatitis' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Lyndon Hernandez, MD, MPH, who contributed to an earlier version of this topic review.
