By: Peter B. Cotton, MD, Professor of Medicine, Digestive Disease Center, Medical University of South Carolina, Charleston, SC
The sphincter of Oddi is a muscular valve that controls the flow of digestive juices (bile and pancreatic juice) through ducts from the liver and pancreas (the Ampulla of Vater) into the first part of the small intestine (duodenum). “Sphincter of Oddi dysfunction (SOD)” describes the situation when the sphincter does not relax at the appropriate time (due to scarring or spasm). The back-up of juices causes episodes of severe abdominal pain. The diagnosis is often considered in patients who present with recurrent attacks of pain after surgical removal of the gall bladder (cholecystectomy), and in some who suffer from recurrent attacks of unexplained pancreatitis. More than half a million cholecystectomies are performed annually in the United States, and 10–20% of these patients present afterwards with continuing or recurrent pains.
About half of these patients will have some impressive objective findings on laboratory studies or imaging (e.g. abnormal liver enzymes on blood testing, or a dilated bile duct on an Ultrasound or CT scan), to suggest definite pathology, such as a stone in the bile duct. These patients are categorized by the Milwaukee classification as SOD Types I and II. MRCP (magnetic resonance cholangio-pancreatography) is nowadays a good non-invasive test for checking on the biliary and pancreatic drainage systems.
When symptoms are severe, and the laboratory and scanning findings are impressive, standard treatment is to perform an endoscopic procedure called endoscopic retrograde cholangiopancreatography (ERCP). This is done under sedation by experts trained in the technique. They pass an instrument (under sedation or anesthesia) down to the duodenum, where the bile duct and pancreatic ducts drain. They inject dye through the Ampulla of Vater into the ducts, and treat what is found, usually by cutting the muscular sphincter (sphincterotomy) to remove any stones or to relieve any scarring or spasm of the sphincter.
Patients with a similar pain problem, but who have little or no abnormalities on blood tests and standard scans (including MRCP), are categorized as SOD type III, with the supposition that episodes of pain are due to intermittent spasm of the sphincter. These patients are very difficult to evaluate and to manage effectively. Indeed some physicians are skeptical of its existence of SOD III, or assume that it is only a small part of a broader problem of a functional digestive disturbance such as irritable bowel syndrome.
A very important problem in this context is that these ERCP procedures carry a significant risk of complications. In particular, ERCP (with or without SOM) can cause an attack of pancreatitis in 5–10% of cases. Whilst most of these result in only a few days in hospital, about 1% of patients suffer a major attack, with weeks or months in hospital. Sphincterotomy also carries a small risk of other severe complications such as bleeding and perforation, and the possibility of delayed stenosis due to scarring.
Because of the risks of ERCP, patients with suspected SOD III are usually advised to try medical treatments first. Some respond to the use of anti-spasmodic drugs and/or anti-depressants that modulate the pain pathways. There have been trials of other medical therapies, such as calcium channel blocking drugs. Despite a few encouraging reports, these modalities have not proven to be effective generally, and are not widely used.
Patients who fail these approaches (at least those with severe symptoms) are usually sent to specialists at tertiary referral centers for further evaluation. This may involve an Endoscopic Ultrasound study to look for minor changes in the pancreas, and MRCP (if not already performed). If nothing else is found, ERCP is recommended to check that there are no subtle structural abnormalities in the papilla, biliary tree or pancreas, and to allow measurement of the actual pressure in the sphincter, by performance of Sphincter of Oddi manometry (SOM). The results of SOM are used to decide whether to perform treatment (at the same ERCP examination), by sphincterotomy of the biliary and/or pancreatic sphincters. SOM is not widely available, and the results are not consistently predictive of the outcome of treatment. In general it appears that biliary sphincterotomy provides benefit in 70% of these patients, at most.
Clinical Study
These uncertainties in how best to diagnose and to treat “suspected sphincter of Oddi dysfunction” (and the risks involved) mandate further scientific investigation. The National Institutes of Health has recently funded an important study called “EPISOD” in 6 major Gastroenterology centers in USA.
Essentially, patients with burdensome pains after cholecystectomy who fulfill the Rome III criteria for sphincter of Oddi dysfunction undergo extensive evaluation for functional and psychiatric disorders. If they consent to the study, they undergo ERCP with SOM, and are randomized to biliary and/or pancreatic sphincterotomy, or to a sham procedure, regardless of the manometry findings. Their clinical course is monitored for up to 4 years. The studies are being conducted at centers located in:
Baltimore, MD
Birmingham, AL
Charleston, SC
Indianapolis, IN
Minneapolis, MN
Seatle, WA
Additional details are available at the NIH website at www.clintrials.gov.
Update: Sphincter of Oddi dysfunction research study needs patients
We have an NIDDK-funded randomized sham-controlled study designed to see which (if any) patients with “Sphincter of Oddi Dysfunction III” respond to sphincter ablation, and which clinical and manometry factors predict the outcome.
The study is progressing well with 70 subjects randomized (the largest number ever in a randomized trial in SOD), but we need 214. So, this is a request to consider referring suitable subjects to one of the 7 active sites.
The basic eligibility criteria are: disabling post-cholecystectomy pain, aged 18-65, no prior pancreatitis or previous sphincter treatment, normal anatomy, normal EGD and scans (bile duct <9mm), failed treatment with PPIs and antispasmodics, liver tests and amylase/lipase <2-3X normal, no daily narcotics, not suicidal.
After informed consent and detailed clinical documentation, subjects undergo ERCP with biliary and pancreatic manometry. They are then randomized to sphincterotomy or sham (2:1 sphincterotomy versus sham). regardless of the manometry results. Those patients randomized to the sphincterotomy arm and who have raised pancreatic sphincter pressures are randomized again to biliary or to biliary and pancreatic sphincterotomy. All subjects get a small temporary pancreatic stent. Patients, caregivers, and research coordinators are blinded to the treatment allocation. Success is defined by substantial reduction in pain burden at 1 year (without any repeat intervention).
Details of the protocol and site contacts are available at www.clinicaltrials.gov. Thank you.
Peter B Cotton
Professor of Medicine, Digestive Disease Center, Medical University of South Carolina, Charleston.
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