No other causes for pancreatitis are usually found in these patients, and they may be classified as having idiopathic acute recurrent pancreatitis IARP 36 , However, the true incidence of pancreatitis caused by SOD is unknown.
When both the pancreas and biliary sphincters are involved, the abdominal pain may be more diffuse and both hepatic and pancreatic enzyme elevation can occur. The diagnosis of SOD is challenging, but history, physical exam, relevant labs, and imaging studies are critical. Some view SOD as a structural abnormality while others view it as a functional disorder.
A classification system for SOD as a structural abnormality was established in These criteria were meant to make the diagnostic evaluation more applicable to clinical practice and, whenever possible, avoid invasive procedures by emphasizing non-invasive imaging of CBD diameter. Earlier studies showed higher rates of depression, obsessive compulsive disorders, and anxiety in patients with type 3 SOD when compared with controls Conversely, a randomized, controlled trial of SOD type 3 patients showed that psychosocial disability in patients with severe symptoms may not be different than in the general population In the past, non-invasive testing to diagnose SOD included quantitative hepatobiliary scintigraphy to assess biliary flow 42 — 44 , endoscopic ultrasound, or magnetic resonance cholangiopancreatography with secretin injection However, these tests are neither sensitive nor specific for SOD.
During SO manometry, a catheter is inserted into the duodenum and calibrated to 0 mmHg. Prior to the procedure, patients should avoid agents that inhibit SO function, such as anticholinergics, nitrates, and calcium-channel blockers, and those that stimulate it, such as opiates and cholinergics.
Therefore, the use of SO manometry as a gold-standard test remains controversial. Furthermore, isolated basal pressures cannot differentiate between SO motor disturbances and anatomical stenosis. Certain populations, such as patients who have undergone cholecystectomy 32 , are predisposed to SOD In subjects with an intact gallbladder, CCK inhibits SO phasic wave activity, but 6 months after cholecystectomy, CCK fails to inhibit this activity It is postulated that the gallbladder acts as a backflow reservoir for bile to dampen sudden increases in pressure resulting from physiologic or extra-physiologic ductal obstruction 56 — Luman and colleagues demonstrated that patients with postcholecystectomy syndrome had elevated basal SO pressure, retrograde phasic wave contraction, and an increase in phasic wave frequency greater than seven contractions per minute tachyoddia It is unclear if postcholecystectomy patients are susceptible to developing SOD because of elevated pressures, altered SO motility, or both.
Sphincter of Oddi dysfunction has also been linked to agenesis of the gallbladder 61 , preoperative cholelithiasis 25 , gallstone lithotripsy 62 , liver transplantation 63 , and alcoholism Delayed emptying of the biliary tract related to hypothyroidism suggests another risk factor for SOD 65 , Evans and colleagues reported that patients with IBS who undergo cholecystectomy are more likely to demonstrate a blunted response to sphincter-relaxing properties of CCK compared with postcholecystectomy patients without IBS Sphincter of Oddi dyskinesia occurs more frequently in women than in men, and animal models offer some insight.
In the prairie dog, CCK increases SO phasic wave frequency in both sexes, but amplitude increases were significantly greater in females than in males Exogenous agents play an additive role in populations at risk for SOD. Opiates are known to alter flow through the SO.
In the absence of a gallbladder, morphine, meperidine, and pentazocine increase biliary pressure in opossums Behar and Biancani found that leucine and methionine-enkephalin caused an initial contraction followed by a prolonged relaxation of the cat SO, suggesting that endogenous delta opioid agonism is involved in increasing flow through the sphincter 72 , The naloxone inhibitory effect suggests that the mu opioid receptor is involved, while the absence of naloxone antagonism on SO basal pressure may be non-mu opioid receptor mediated.
Thus, morphine increases the amplitude and frequency of the phasic wave via mu opioid receptors as well as basal pressure via non-mu opioid receptors of the SO 74 , These effects have also been demonstrated with fentanyl 76 and codeine Morphine shows limited effect on the SO in patients prior to cholecystectomy, whereas it caused a notable rise in basal sphincter pressure postoperatively The magnitude of transaminase elevation associated with morphine has been reported as high as 65 times above normal in patients without a gallbladder Mousavi and colleagues demonstrated that chronic opiates induce SOD compared with case controls 79 , and several authors have documented asymptomatic, dilated CBDs in patients addicted to opiates 80 — The effects of tramadol, buprenorphine, pentazocine, and pethidine have been evaluated with SO manometry.
Pentazocine increased the duration of sphincter contraction and ductal pressure while tramadol, buprenorphine, and pethidine did not 83 , Eluxadoline, a mixed opioid receptor modulator with mu and kappa opioid receptor agonist effects and delta opioid receptor antagonist effects that was recently approved by the FDA for IBS with diarrhea, was linked to a small number of non-serious cases of SO spasm and pancreatitis in the phase 3 studies of this medication Among 1, patients exposed to eluxadoline in these trials, 8 0.
Importantly, all cases of eluxadoline-associated SO spasm occurred in patients who did not have gallbladders and were more common with mg twice daily BID compared with 75 mg BID. One case of pancreatitis was associated with biliary sludge while the other three were associated with heavy alcohol use. Opiates have been reported to incite pancreatitis, and their effects on the SO represent the most likely etiology The mu antagonist naloxone reduces the severity of pancreatitis induced by intraductal injection of trypsin—bile mixture in dogs.
In the opossum, Chen and colleagues induced pancreatitis when they combined simulated SOD by PD ligation mimicking the opiate effect with pharmacologically stimulated pancreatic secretion In humans, drug rechallenge 89 , 90 with heroin 91 , 92 , codeine 93 — 95 , tapentadol, 1 and loperamide 96 — 99 have established a link with these drugs and acute pancreatitis.
Loperamide inhibits the normal contractile response of the gallbladder to CCK and, in patients with short bowel syndrome, reduces pancreatic and biliary output Certain exogenous agents relax the SO, reducing its pressure and resistance. Nifedipine has been shown to reverse opiate-induced effects on the SO and improve pain associated with SOD in a short-term study GTN has been used to assist removal of lodged CBD stones without endoscopic papillary dilatation or endoscopic papillotomy and decreased both basal SO pressure as well as the amplitude and frequency of SO phasic wave contractions in a non-randomized, controlled clinical trial Intravenous somatostatin was shown to reduce mean SO basal pressures in patients with acute alcoholic pancreatitis One prospective study of patients with biliary SOD defined by clinical and laboratory data evaluated the combination of a low-dose tricyclic antidepressants, nifedipine, and GTN.
If there was no improvement after 3—6 months, patients were offered biliary sphincterotomy. Although promising, opiates were allowed during this study, confounding the determination of symptom improvement due solely to interventions. However, it is not effective, and may be harmful, in patients with type 3. The evaluating predictors and interventions in sphincter of Oddi dysfunction trial was a landmark study for treatment of type 3. This was a multicenter, sham-controlled, randomized trial in patients with pain after cholecystectomy, without abnormalities on imaging or laboratory studies, and no prior SO treatment.
Participants underwent sphincterotomy or sham sphincterotomy for abdominal pain. The investigators concluded that performing a sphincterotomy in patients with type 3 SOD was ineffective As a result, endoscopists are shifting away from performing sphincterotomy in these patients.
There are limited studies evaluating the role of PD stenting and sphincterotomy in patients with pancreatic SOD. Jacob and colleagues found a significant reduction in the incidence of recurrent acute pancreatitis in those who were stented Another study found no difference in preventing recurrent pancreatitis when dual sphincterotomy was compared with either pancreatic or biliary sphincterotomy Sphincter of Oddi dysfunction denotes impaired fluid flow through the SO, either by a fixed stenosis or disordered muscular control dyskinesia.
Gallbladder function appears to play a critical role in SO mechanics, and patients without a gallbladder are more likely to experience SOD. Other potential contributing factors include female gender, hypothyroidism, IBS, prior pancreatitis, and exogenous medications.
The data supporting a link between opiates and SOD are clear and reproducible, and the resulting clinical syndromes, especially in postcholecystectomy patients, include abdominal pain with sudden, yet reversible, elevations in liver enzymes as well as acute pancreatitis.
Different opiate agents appear to have varying effects on SO basal and phasic contractions. While exogenous mu opioid agonists negatively affect flow through the SO, endogenous enkephalins possibly delta agonists may improve flow through the sphincter. Endoscopic sphincterotomy remains the treatment of choice for select patients confidently diagnosed with SOD. However, increased awareness by caregivers of risk factors for SOD provides opportunities for diagnosis and intervention, including avoidance of potential precipitating agents, especially in the absence of a gallbladder.
All authors approved the final draft of this manuscript for submission. SP is the guarantor of the article. PC serves as a scientific consultant for Allergan plc. BC has served as an advisor, consultant, or speaker for Actavis, Inc. EA and SL have no relevant disclosures to report. Writing and finalization of the manuscript content was performed exclusively by the authors. PC has previously acted as a consultant to Allergan plc and requested assistance in finalization of the reference list, formatting the manuscript, and support of submission.
Allergan has a contract with Complete HealthVizion, Inc. Williamson JB. Effect of morphine after cholecystectomy. Br Med J Smyth MJ. Exploration of the common bile duct for stone. Drainage with T-tube and cholangiography. Br Med J — Am J Anat — Leung WD, Sherman S. Endoscopic approach to the patient with motility disorders of the bile duct and sphincter of Oddi. Gastrointest Endosc Clin N Am — Google Scholar.
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Symptoms of SOD Symptoms include: abdominal pain located in mid- or right-upper abdomen might also be felt in the back and shoulders can last anywhere from several minutes to several hours can be a mild, dull throbbing pain, or Standard ultrasound and CT scans are used to look for structural causes, but are not completely accurate. One of these should be used before considering more invasive and risky procedures like ERCP. Another test HIDA scanning is sometimes used to detect poor emptying of the bile duct due to sphincter activity, and botox injection into the sphincter has been explored as a test for over-activity.
When attacks of pain cause considerable disturbance with life activities, a decision has to be made whether to cut the sphincter sphincterotomy during ERCP to either remove stones in the ducts or to improve drainage.
ERCP is rarely indicated if gallbladder is not removed. When sphincter of Oddi manometry has confirmed that the pressures are high, sphincterotomy gives good relief in more than half of patients. There is also the possibility of recurrent symptoms after months or years due to scarring of the sphincterotomy.
Further cutting repeat sphincterotomy is sometimes possible, but there are limits; surgical treatment with a transduodenal sphincteroplasty —an open surgery performed under general anesthesia where an incision is made through the first part of the small intestine and the pancreas— may be necessary.
These two types of sphincter of Oddi dysfunction can be further divided into three categories. With category I, patients have pain, abnormal blood test results, delayed drainage of contrast during ERCP, and abnormal findings on imaging dilated common bile duct for biliary type I and dilated pancreatic duct for pancreatic type I.
With category II, patients have pain and only one or two of the preceding criteria. With category III dysfunction, there are no clear lab findings or abnormalities, and the only sign of a problem is abdominal pain.
The symptoms of sphincter of Oddi dysfunction may come and go over time. They also may vary in severity from one occurrence to the next. Common symptoms include:. But they suspect it may be related to microlithiasis the presence of microscopic stones in the bile and inflammation of the first section of the small intestine. It appears that some people are more at risk of developing sphincter of Oddi dysfunction than others.
Additionally, middle-aged women also might be at an increased risk for the condition. If you present symptoms of sphincter of Oddi dysfunction to your doctor, they will try to rule out other possible causes of your symptoms. Some serious conditions they must rule out include cancer of the pancreas or bile ducts, peptic ulcer disease, or stones in the bile ducts. Heart conditions, such as angina or ischemia, can also cause pain that comes from the abdomen.
Your doctor may run blood tests or use imaging studies to help with the diagnosis. Ultrasound, hepatobiliary scintigraphy, or magnetic resonance cholangiopancreatography MRCP may be ordered. You will be sedated for the manometry procedure. Sphincter of Oddi manometry is the gold standard for diagnosis of SOD. However, you may notice that some foods trigger your symptoms worse than others.
Some people feel ill every time they eat, while others are affected by specific foods only on rare occasions. An elimination diet involves systematically removing foods from your diet that are known to trigger sphincter of Oddi dysfunction symptoms in some people. These include:. You can find elimination diet instructions here. Keep a food diary to record what kinds of, and how much, food and drinks you consume at each meal throughout the day.
Note how you feel after eating and drinking. Some people with sphincter of Oddi dysfunction report improved symptoms when they juice or blend their foods during the elimination stage.
This makes it easier for the body to absorb nutrients and puts less stress on the sphincter of Oddi.
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