Sphincter of Oddi Dysfunction

Definition, Etiology, PathogenesisTop

Sphincter of Oddi dysfunction (SOD) refers to an abnormal function or structure of the sphincter of Oddi that results in abnormalities in the flow of bile and pancreatic juices. Disturbances of motor function of the sphincter of Oddi may affect the biliary portion of the sphincter, pancreatic portion of the sphincter, or both.

SOD is relatively difficult to diagnose and requires exclusion of other biliary/pancreatic disorders. The definitive diagnostic test (manometry) is not widely available.

SOD most frequently develops in patients with a history of cholecystectomy.

Clinical Features and Natural HistoryTop

SOD is classified based on the dominant manifestations as:

1) Biliary type, with dominant clinical features of bile duct stenosis (similar to choledocholithiasis).

2) Pancreatic type, with dominant clinical features of pancreatitis (acute epigastric pain, usually postprandial) and episodes of acute pancreatitis.

Classification: Table 1.

A typical symptom of dysfunction of the sphincter of Oddi is epigastric or right upper quadrant abdominal pain that lasts from 30 minutes to several hours and is referred to the back or the shoulder. It is triggered by food, narcotic analgesics, or both. Other pain features are discussed under Diagnostic Criteria, below.

The pain may appear shortly or several years after cholecystectomy and may resemble preoperative pain. On physical examination, mild epigastric or right upper quadrant abdominal tenderness is found. Some patients may have episodes of typical acute pancreatitis, which are often recurrent.

DiagnosisTop

Diagnostic Tests

1. Laboratory tests: Fewer than 50% of patients have elevated blood enzyme levels. Depending on the type of dysfunction, these include liver enzymes (aminotransferases, alkaline phosphatase [ALP]), pancreatic enzymes (amylase, lipase), or both these types; their transient elevation is seen during pain attacks.

2. Imaging studies are used to exclude gallstones and strictures. Ultrasonography or computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP) may reveal dilatation of bile ducts or of the pancreatic duct, which is used in the classification of SOD (Table 1) and treatment planning.Evidence 1Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered because of methodology limitations, imprecision, and heterogeneity of the intervention. Pereira SP, Gillams A, Sgouros SN, Webster GJ, Hatfield AR. Prospective comparison of secretin-stimulated magnetic resonance cholangiopancreatography with manometry in the diagnosis of sphincter of Oddi dysfunction types II and III. Gut. 2007 Jun;56(6):809-13. Epub 2006 Sep 27. PubMed PMID: 17005767; PubMed Central PMCID: PMC1954855. Darweesh RM, Dodds WJ, Hogan WJ, et al. Efficacy of quantitative hepatobiliary scintigraphy and fatty-meal sonography for evaluating patients with suspected partial common duct obstruction. Gastroenterology. 1988 Mar;94(3):779-86. PubMed PMID: 3276574. Warshaw AL, Simeone J, Schapiro RH, Hedberg SE, Mueller PE, Ferrucci JT Jr. Objective evaluation of ampullary stenosis with ultrasonography and pancreatic stimulation. Am J Surg. 1985 Jan;149(1):65-72. PubMed PMID: 3881057.

3. Manometry of the sphincter of Oddi confirms the diagnosis but is rarely available, technically demanding, invasive, and associated with high complication rates (~30% risk of acute pancreatitis). Most commonly, it is performed as a component of endoscopic retrograde cholangiopancreatography (ERCP) (ERCP without manometry should not be performed in the diagnostic workup of SOD because of the risk of triggering iatrogenic acute pancreatitis). The criterion of abnormal function of the sphincter of Oddi is a resting pressure >40 mm Hg. Manometry may be justified in type II or type III biliary dysfunction (after an unsuccessful attempt of pharmacologic treatment) and in pancreatic-type dysfunction.Evidence 2Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to heterogeneity of correlations between accuracy of sphincter of Oddi manometry vs clinical and radiologic pictures. McLoughlin MT, Mitchell RM. Sphincter of Oddi dysfunction and pancreatitis. World J Gastroenterol. 2007 Dec 21;13(47):6333-43. Review. PubMed PMID: 18081221; PubMed Central PMCID: PMC4205451. Pereira SP, Gillams A, Sgouros SN, Webster GJ, Hatfield AR. Prospective comparison of secretin-stimulated magnetic resonance cholangiopancreatography with manometry in the diagnosis of sphincter of Oddi dysfunction types II and III. Gut. 2007 Jun;56(6):809-13. Epub 2006 Sep 27. PubMed PMID: 17005767; PubMed Central PMCID: PMC1954855. Eversman D, Fogel EL, Rusche M, Sherman S, Lehman GA. Frequency of abnormal pancreatic and biliary sphincter manometry compared with clinical suspicion of sphincter of Oddi dysfunction. Gastrointest Endosc. 1999 Nov;50(5):637-41. PubMed PMID: 10536318. Manometry helps to predict the success of invasive therapy, as patients with a high resting pressure may see improved symptoms with sphincterotomy. If manometry is unavailable or has been unsuccessful, a noninvasive morphine-neostigmine test may be performed.

4. MRCP is performed to exclude gallstones and biliary duct stenosis.

5. Endoscopy: Duodenoscopy with the evaluation of the papilla of Vater is performed to exclude carcinoma of the ampulla of Vater. Biopsy or brush sample collection for microscopy is performed when necessary.

6. Endoscopic ultrasonography (EUS) may be used to detect small gallstones and assess the papilla of Vater to reliably exclude organic lesions.

Diagnostic Criteria

Confirmation of the diagnosis of SOD is possible only on the basis of manometry, but this is rarely performed. In practice, the diagnosis and classification are based on clinical features and results of laboratory tests and imaging studies. According to the Rome IV diagnostic criteria, SOD is diagnosed in patients with episodes of epigastric and/or right upper quadrant abdominal pain who fulfill all of the following:

1) The pain increases to reach a constant level and last ≥30 minutes.

2) Symptoms recur at varying intervals (not daily).

3) The pain is severe enough to disturb daily living activities or to make the patient seek urgent medical help.

4) The pain is not significantly (<20%) related to defecation.

5) The pain is not significantly (<20%) reduced by changing the patient’s position.

6) The pain is not significantly (<20%) reduced by antacids or gastric acid secretion inhibitors.

Supportive criteria: One or more of the following:

1) The pain is accompanied by nausea and vomiting.

2) The pain is referred to the back or to the right subscapular area.

3) The pain wakes the patient from sleep.

In patients with normal serum amylase and lipase levels, the diagnosis of biliary-type dysfunction is made (auxiliary criterion: elevated levels of aminotransferase, ALP, or conjugated bilirubin showing an evident temporal relationship with ≥2 pain episodes). In patients with elevated serum amylase and lipase levels, the diagnosis of pancreatic-type dysfunction is made.

Differential Diagnosis

Other causes of abdominal pain. If cholelithiasis and malignancy have been excluded using imaging studies and an attempt of treatment with gastric secretion inhibitors has failed, the likelihood of SOD is significantly increased.

TreatmentTop

1. Pharmacotherapy: The efficacy of pharmacotherapy is poorly documented. It may be useful mainly in patients with mild SOD and moderate clinical manifestations and in all patients with type III dysfunction. Agents include transdermal or sublingual nitroglycerin, oral nifedipine, and oral trimebutine.Evidence 3Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to some heterogeneity among mostly observational studies. Staritz M. Pharmacology of the sphincter of Oddi. Endoscopy. 1988 Aug;20 Suppl 1:171-4. Review. PubMed PMID: 3049055. Döbrönte Z, Simon L, Patai A. [Management of Oddi sphincter dyskinesis. Results of drug therapy and sphincterotomy]. Orv Hetil. 1995 Oct 1;136(40):2165-7. Hungarian. PubMed PMID: 7566950. Khuroo MS, Zargar SA, Yattoo GN. Efficacy of nifedipine therapy in patients with sphincter of Oddi dysfunction: a prospective, double-blind, randomized, placebo-controlled, cross over trial. Br J Clin Pharmacol. 1992 May;33(5):477-85. PubMed PMID: 1524959; PubMed Central PMCID: PMC1381433. Craig AG, Toouli J. Slow release nifedipine for patients with sphincter of Oddi dyskinesia: results of a pilot study. Intern Med J. 2002 Mar;32(3):119-20. PubMed PMID: 11885840.

2. Endoscopic treatment: The benefits of endoscopic sphincterotomy are equivocal. To date it has been recommended in patients with type I dysfunctionEvidence 4Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to methodologic limitations. Cotton PB, Durkalski V, Romagnuolo J, et al. Effect of endoscopic sphincterotomy for suspected sphincter of Oddi dysfunction on pain-related disability following cholecystectomy: the EPISOD randomized clinical trial. JAMA. 2014 May;311(20):2101-9. doi: 10.1001/jama.2014.5220. PMID: 24867013. Sgouros SN, Pereira SP. Systematic review: sphincter of Oddi dysfunction--non-invasive diagnostic methods and long-term outcome after endoscopic sphincterotomy. Aliment Pharmacol Ther. 2006 Jul 15;24(2):237-46. doi: 10.1111/j.1365-2036.2006.02971.x. PMID: 16842450. and in patients with type II or type III dysfunction and elevated sphincter pressures found on manometry.Evidence 5Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to methodologic limitations. Cotton PB, Durkalski V, Romagnuolo J, et al. Effect of endoscopic sphincterotomy for suspected sphincter of Oddi dysfunction on pain-related disability following cholecystectomy: the EPISOD randomized clinical trial. JAMA. 2014 May;311(20):2101-9. doi: 10.1001/jama.2014.5220. PMID: 24867013. Sgouros SN, Pereira SP. Systematic review: sphincter of Oddi dysfunction--non-invasive diagnostic methods and long-term outcome after endoscopic sphincterotomy. Aliment Pharmacol Ther. 2006 Jul 15;24(2):237-46. doi: 10.1111/j.1365-2036.2006.02971.x. PMID: 16842450. Between 10% and 20% of sphincterotomies are complicated by acute pancreatitis.

3. Surgical treatment: Transduodenal sphincteroplasty with pancreatic septoplasty, which is rarely performed and used mainly in patients with recurrent stenosis after endoscopic treatment.Evidence 6Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to the observational nature of studies. Nussbaum MS, Warner BW, Sax HC, Fischer JE. Transduodenal sphincteroplasty and transampullary septotomy for primary sphincter of Oddi dysfunction. Am J Surg. 1989 Jan;157(1):38-43. PubMed PMID: 2910125. Stephens RV, Burdick GE. Microscopic transduodenal sphincteroplasty and transampullary septoplasty for papillary stenosis. Am J Surg. 1986 Dec;152(6):621-7. PubMed PMID: 3789286. Tzovaras G, Rowlands BJ. Transduodenal sphincteroplasty and transampullary septectomy for sphincter of Oddi dysfunction. Ann R Coll Surg Engl. 2002 Jan;84(1):14-9. PubMed PMID: 11890620; PubMed Central PMCID: PMC2503761. Acute pancreatitis is the most common complication of endoscopic sphincterotomy.

TablesTop