How can I be sure that the patient has sphincter of Oddi dysfunction?

The most common symptoms are epigastric pain; right upper quadrant pain, sometimes radiating through or around to the back; more rarely, left upper quadrant pain; and nausea.

Sphincter of Oddi dysfunction (SOD) can present in two main ways: (1) the postcholecystectomy pain syndrome (gallbladder-type pain but no gallbladder); or (2) unexplained pancreatitis (esp. IRAP – idiopathic recurrent acute pancreatitis [lipase/amylase greater than three times upper limit of normal]).

The pain syndrome may be either in the form of a biliary type pain or a pancreatic-type pain. This may overlap with the IRAP presentation, but the former is more right-sided and the latter more likely to be central and to radiate straight through to the back. Objective signs (bile or pancreatic duct dilation, elevated liver/pancreas enzymes) can be present or absent. The more objective and compelling these objective signs are, the more likely the diagnosis of a pancreatobiliary pain origin is correct and, consequently, the more likely the response will be to sphincterotomy. Sphincter of Oddi manometry or SOM (sphincter pressure measurements) at ERCP (endoscopic retrograde cholangiopancreatography) is recommended to confirm the diagnosis, except in those with very objective presentations (both duct dilation and enzyme elevations, so called “type I” SOD), wherein ERCP with empiric sphincterotomy may be acceptable. Some of these latter patients have more of a sphincter “stenosis” rather than “spasm” or dysfunction but are treated similarly with sphincterotomy.

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Those without any objective signs (normal/near normal imaging and labs), do not appear to respond to sphincterotomy; these patients, previously described as “type III SOD”, should not undergo ERCP, regardless of whether SOM is available, based on recent results from the NIH-sponsored EPISOD trial.

The second main presentation of SOD is IRAP. “Recurrent” is stipulated because most (~80%) patients with an episode of unexplained acute pancreatitis do not suffer a recurrence and testing for SOD is not recommended until a second (or even third) attack occurs. The definition of idiopathic is a point of controversy but in general is defined as “no gallstones, no alcohol, no hypertriglyceridemia/hypercalcemia, normal anatomy, and no medications implicated.”

For patients with pancreas divisum, because most of their pancreas does not drain through the major papilla, major papilla SOD is also not relevant to IRAP. Whether patients have to have their gallbladder (empirically) removed and/or have genetic testing before being tested for SOD is controversial, but many use the IRAP term even if these have not been done, and believe sphincter manometry is reasonable in that setting. These acute pancreatitis attacks generally require serum lipase and/or amylase more than three timesthe upper limit of normal, or imaging evidence of acute pancreatitis. More modest elevations are often mislabelled by referring doctors as “pancreatitis” but are better categorized as type II pancreatic SOD.

There may also be an increase in SOD in those with chronic pancreatitis (vs IRAP), and some have advocated assessing for SOD in both populations. There is more evidence for its usefullness in IRAP than in chronic pancreatitis, however. For (unexplained) chronic pancreatitis, most multivariate analyses show that these patients respond significantly less frequently to sphincterotomy than other patients with suspected SOD, and so the role of SOD-linked investigations and treatments is not as clear in this setting.

A tabular or chart listing of features and signs and symptoms

Postcholecystectomy right upper quadrant or epigastric pain, usually either random and episodic, or meal-related, and occurring almost exclusively in women (greater than 90%), or IRAP.

Less common presentations include unexplained left upper quadrant pain, unexplained nausea, unexplained chronic pancreatitis, unexplained duct dilation. These presentations are more likely to have alternative explanations, rather than SOD, for the symptoms and/or findings.

SOD is usually grouped into several categories based on a combination of clinical symptoms, imaging tests, and laboratory results (SeeTable I.) The diagnosis of a biliary-type SOD usually requires that the gallbladder has already been removed.

Table I.
Type Clinical criteria Radiographic and laboratory criteria
Biliary Type I Biliary-type pain Bile duct dilated more than 10 mm and
Elevated ALT, AST, or alk phos on at least one occasion
Biliary type II Biliary-type pain Bile duct dilated more than 10 mm or
Elevated ALT, AST, or alk phos on at least one occasion
Biliary Type III Biliary-type pain Normal imaging and liver chemistries
Pancreatic Type I Relapsing pancreatitis Dilated pancreatic duct and
Elevations in amylase of lipase >3 times the upper limit of normal
Pancreatic Type II Relapsing pancreatitis Dilated pancreatic duct or
Elevations in amylase of lipase >3 times the upper limit of normal
Pancreatic Type III Pancreatic pain only Normal imaging and pancreatic enzymes

Alternative diagnoses for the patients with unexplained postcholecystectomy pain can include occult choledocholithiasis, irritable bowel syndrome (right colon or duodenal spasms or right-sided visceral hypersensitivity, right-sided stool/constipation), dyspepsia (ulcer and non-ulcer), chronic pancreatitis, atypical reflux/gas, inflammation/stretch of the liver capsule (sometimes seen with fatty liver and other processes), adhesions, scar-related pain, neuropathic pain (e.g., from thoracic disc disease), and costochondral/abdominal muscle musculoskeletal pain (See Table II.).

Table II.
Other diagnoses Selected differentiating factors
Irritable bowel syndrome (IBS) Pain related to bowel movements
Associated constipation, diarrhea, postprandial urgency, or other symptoms
Associated bloating
Changing/fleeting location of pain
Response to antispasmodics, neuromodulators
Other risk factors for visceral hypersensitivity, such as long-standing narcotics
Dyspepsia Response to antacids, Hp eradication, stopping NSAID, or promotility medications
Nausea-predominant symptoms
Associated reflux-type symptoms or radiation into chest
Postprandial distress/bloating
Abnormal EGD
Musculoskeletal and neuropathic pain Pain positional
Little to no relationship to meals
Associated back pains
Physical exam rib tenderness, reproduction with spine percussion, or increase tenderness when muscles tensed
Chronic pancreatitis Risk factors for chronic pancreatitis
Centrally located pain, often radiating to the back
Structural (CT/MRI/EUS/ERCP) or functional (endocrine/exocrine) abnormality in the pancreas
+/- Response to pancreatic enzymes

Unexplained ductal dilation, and/or elevated liver and/or pancreatic enzyme levels, have a widerdifferential diagnosis, including stones, strictures (benign/malignant), ampullary neoplasms, medication-related cholestasis and intrinsic liver disease (esp., fatty liver), chronic pancreatitis, age-related ductal prominence, narcotic-related ductal dilation, and others.

Relapsing or recurrent acute pancreatitis may be explained by genetics (esp., CFTR, SPINK1, PRSS1), pancreas divisum, occult neoplasms, occult biliary lithiasis, and unreported medicines or alcohol.

How can I confirm the diagnosis?

Other than ERCP with SOM, there is no accurate (noninvasive) testing for SOD. Therefore, much of the testing is aimed at making sure the pain or pancreatitis is truly “unexplained” or idiopathic. The list of tests to “rule out” other possibilities is different for different patients, depending somewhat on what associated symptoms are present (e.g., nausea, altered bowel habit, weight loss, age). By the time patients present for ERCP and manometry, patients have generally had multiple empiric drug trials (proton pump inhibitors (PPI), antispasmodics) that have failed, and had multiple normal imaging and endoscopic tests.

First, ultrasound and/or CT of the abdomen and an upper endoscopy (usually with H. pylori testing) are usually performed. Empiric stoppage of NSAIDs (nonsteroidal anti-inflammatory drugs) and/or trials of a PPI are generally recommended if the above are normal, along with a set of liver and pancreas enzymes. The latter are best done while pain-free and repeated within 24 to 48 hours after a pain attack, to assess if rises occur with pain and toclarify if abnormalities seen are episodic versus chronic.

MRCP (magnetic resonance cholangiopancreatography) or EUS (endoscopic ultrasound) are performed next to accurately rule out strictures and stones, pancreas divisum, and chronic pancreatitis. EUS may be more sensitive for small tumors, ampullary lesions, and subtle chronic pancreatitis, and so, in older patients, patients with more chronic pain or other chronic pancreatitis risk factors (e.g., remote alcohol and smoking), or patients with unexplained duct dilation, EUS may be preferred, even if MRCP has already been done.

Selectively, in some patients, colonoscopy, gastric emptying study, and other empiric trials (antiemetics, osmotic laxatives, antibiotics for bacterial overgrowth, neuromodulators/anxiolytics) may be done. Nausea-predominant presentations may require a different workup (brain imaging, morning cortisol, etc.), as might pain pesentations that include a positional component (back imaging), liver enzymes that are chronically elevated (hepatitis serology and other tests), or pancreatitis (calcium, fasting triglycerides, etc.).

HIDA (hepatobiliary iminodiacetic acid, also called cholescintigraphy scans), which involve nuclear labelling of bile to assess delays in excretion from the duct, have had variable performance in clinical trials involving post-cholecystectomy patients with pain. Unfortunately, the most promising results have been difficult to reproduce, and were mostly based on data gathered in patients with dilated ducts; the latter may be more a population of ampullary stenosis, rather than true sphincter spasm or dysfunction (SOD). Some studies have shown poor correlation with SOM, however. In addition, a study at the Medical University of South Carolina (MUSC) showed that in asymptomatic postcholecystectomy patients, the false positive rate was >20% (40% if 2 scans had to be normal). A few studies showed that scintigraphy results can return to normal after biliary sphincterotomy in suspected SOD patients. Its validity has remained in doubt by experts, especially in type II SOD, especially in patients with nodilated ducts.

By this point in the work-up, the “type” of SOD suspected is known: patients with dilated ducts AND abnormal labs (liver/pancreatic enzymes) are considered type I, and those with either normal imaging or normal labs (but not both) are suspected type II.

There is not good evidence to conclude that type II patients behave differently than those with normal labs and imaging (previously termed type III), although it was long believed that type II patients had intermediate response rates, between the I and III patient groups. In addition, definitions of what separated type II and III in terms of labs or diameter of ducts was not consistent in the literature – for the former, cutoffs have varied from 1.1 times normal, to 1.5 and 2 times normal. Because the bile duct can get bigger with higher age, longer duration after cholecystectomy, and narcotics, what is “normal” or expected in these patients also is often unclear.

Suspected SOD, can be categorized further as biliary or pancreatic (e.g., dilated bile duct and pain = type II biliary, elevated pancreatic enzymes and pain = type II pancreatic).

Confirming the diagnosis

Diagnostic ERCP without SOM is of little to no value and has high risks, even if (and, perhaps, especially if), sphincterotomy treatment is not performed. This should not be done.

Stenting the papilla as a therapeutic trial (i.e., as a diagnostic test) is dangerous, with a high rate of post-ERCP pancreatitis (in a study stenting the bile duct) and a high risk of pancreatic ductal damage when stenting the pancreatic duct – this is not recommended.

ERCP, with SOM, looking for basal pressures greater than 40mmHg, is the gold standard for diagnosis in type II SOD, used in major US centers. Other manometric findings (high amplitude contractions, frequent contractions [tachyoddia]), retrograde contractions, etc., with or without hormonal provocation, are less clearly relevant, but sometimes used in other countries as part of the assessment. In clinical trials of type II SOD, high basal pressures (what some termed “stenosis” in trials), predicted response much better than other features (what some termed “dyskinesia” in trials); response rates in the latter were similar to those with normal SOM.

ERCP in this setting is a test that has a 5% to 15% rate of post-ERCP pancreatitis, with about 10% of these being severe: 1 in 1,000 patients will suffer a fatal adverse event. As such, this test is reserved for selected patients after a thorough and frank discussion of the risks and the limits of therapy. It is also generally reserved for those with pain that is having a significant effect on quality of life. As previously stated, temporary stenting is not an acceptable “diagnostic test”.

Tests that need further study

Small series of patients treated with perisphincteric botox (botulinum toxin) injections have been published (using similar dose as is used in esophageal sphincter injections for achalasia) with some promising results. The theory is that disabling the sphincter’s ability to contract with botox may provide months of relief and help predict who would best respond to sphincterotomy. However, the duration and degree of pain relief needed to be considered to have had a “positive response” is not clear. Also, due to the orifice edema that arises after injection, doing this without temporary pancreatic stenting is probably dangerous. Although some studies show that botox responders are more likely to get some relief after sphincterotomy than non-responders, this may simply be due to a repeated placebo effect; placebo-responders are more likely to respond to a second placbo.

“Biliary” MRCP with contrast agents that are excreted into the biliary tree and then exit through the sphincter of Oddi into the duodenum might provide a dynamic impression of drainage through the sphincter. However, this may suffer from the same limitations as HIDA scanning. A few studies have looked at the value of a secretin-stimulated MRCP or EUS to assess pancreatic duct dilation and/or delayed drainage to screen for pancreatic SOD, with modest results.

What other diseases, conditions, or complications should I look for in patients with sphincter of Oddi dysfunction?

Risk factors

Postcholecystectomy. Historically, this is thought to define the pain syndrome, but it is not clear if cholecystectomy is needed for SOD to be present and symptomatic. The gallbladder likely takes up the slack of elevated intraductal pressure from temporary obstruction at the sphincter, thereby reducing pain. After it is removed, SOD-related pain may escalate, or become unmasked. However, this timing of presentation after cholecystectomy may indicate a failure of cholecystectomy at solving the patient’s problem, rather than the post-cholecystectomy state causing the SOD presentation.

Female, under age 60 years. More than 90% of patients fit this demographic, but it is not clear why this is.

There is clearly an overlap with other functional disease, somatization, depression, anxiety, and IBS, but it is not understood if these are “risk factors” or just associated conditions.

For IRAP, it is generally felt that, just as has been seen in pancreas divisum patients, in addition to the structural/obstructive risk factor, there is likely an underlying genetic predisposition to pancreatitis (e.g., CFTR, SPINK-1), in addition to their SOD. Most patients do not have a family history, as IRAP is thought to be due to multi-gene/environment interactions that only reach the threshold for causing symptoms in one or two family members, as well as the fact that some mutations may be sporadic.

Complications of SOD

SOD is generally not a life-threatening condition, but it greatly affects patient quality of life. Most “complications” occur as a result of diagnostic tests, especially ERCP. However, SOD, untreated, can result in pancreatitis in some patients, with its usual sequelae.

What is the right therapy for the patient with sphincter of Oddi dysfunction?

The only known medication treatment comprises antispasmodics, similar to what is used in IBS. Narcotics, long term, can mimic many of the symptoms and signs, and should be tapered if possible, although these may be needed for short-term relief of pain during attacks. The role of neuromodulating drugs (tricyclic antidepressants, etc.) is unclear. These medical therapies have not been specifically studied in SOD, but they are thought to be helpful by many experts.

If these fail, and the quality of life burden warrants the risk, an ERCP with SOM is performed, followed by manometry-directed sphincterotomy. Empiric biliary sphincterotomy for biliary type I SOD is felt to be acceptable, with benefit in more than 80% to 90% of patients. Patients with minimal duct dilation and minimal enzyme elevations, or with atypical or constant pains, however, do not behave as predictably.

Type II SOD therapy is generally dictated by SOM results, in accordance with two randomized trials showing normal SOM patients do just as well with sham as with sphincterotomy. However, in practice, those with clear, marked transient enzyme elevations with pain, or those with markedly dilated ducts, are often treated empirically, in the same way as type I patients.

The term type III SOD should no longer be used. A randomized sham-controlled, blinded, multicentre trial (the EPISOD trial) recently disproved the existence of type III SOD, with the sham group doing just as well, if not better than the sphincterotomy groups; 10-15% of patients developed pancreatitis after ERCP in the trial, despite ERCPs done by experts, with near-universal success in temporary pancreatic stenting. Neither manometry, nor clinical features predicted response; clinical factors did not predict SOM. Dual sphincterotomy performed no better than biliary sphincterotomy alone. The subgroup with mild elevations in liver enzymes and lipase did no better than those with perfectly normal labs, raising questions regarding the benefit of ERCP in borderline type II patients.

ERCPs in these patients, even if SOM is deferred, and even if sphincterotomy is not done, generally should be followed with a temporary (small caliber [3-5F], without internal flanges) pancreatic stent, generally in expert hands. Follow-up (generally by abdominal X-ray in 2-4 weeks) to ensure the temporary pancreatic stent has passed, is needed to avoid duct damage from retained stents (10-20% will not pass spontaneously).

For IRAP, it is felt that the treatment efficacy (of significantly reducing the frequency of acute pancreatitis or of eliminating attacks) is approximately 70% to 90%, with 10% to 30% reporting a recurrent attack after 2 to 3 years. A recent randomized trial showed that biliary sphincterotomy alone, is no better than sham in those with normal pancreatic SOM; those with pancreatic sphincter hypertension were not randomised to a sham arm, however. As previously described, it is likely that these patients also have a genetic predisposition to IRAP, and so the chance of future attacks is not completely eliminated by sphincterotomy, even when manometric SOD is present. A small randomized trial of long-term pancreatic stenting showed a drop in pancreatitis rates from 53% in controls to 11% in the stented group (mean 33 month follow-up); however, long-term pancreatic stenting is no longer considered an acceptable treatment due to irreversible duct damage in some patients, and no randomized trial of pancreatic sphincterotomy has been done in IRAP.

Other treatment options

Balloon sphincteroplasty (endoscopic or percutaneous), dilating the sphincter, likely has a slightly higher risk of causing pancreatitis, and has unclear long-term efficacy. Experts believe sphincterotomy, i.e., cutting the sphincter, is likely safer and more effective.

Surgical sphincteroplasty is reserved for recurrent restenosis or those not able to undergo endoscopic sphincterotomy (e.g., surgically altered anatomy making ERCP not feasible). There is no evidence for duct bypass operations for SOD.

Antispasmodics, neuromodulators, and anxiolytics/antidepressants are helpful in selected patients. All have modest efficacy, likely effective in approximately 50% to 60% of patients.

Many patients feel that avoidance of large meals, fatty meals, and/or spicy meals achieves some symptom response; however, there is no evidence base for this. There is some neural and hormonal basis to the first two, in terms of less stimulation of the sphincter and the pancreas, but dietary restriction should not be overly aggressive because it may lead to nutritional issues and weight loss from food avoidance, without evidence of efficacy.

Pancreatic enzymes appear to anecdotally help in some patients, although there is no evidence base for their use. These may help reduce pancreatic stimulation in some patients with SOD, but there is also likely a significant placebo response component. Downsides to their use, include cost and the inherent mislabelling of these patients as having “chronic pancreatitis”, as this diagnosis may be implied when enzymes are prescribed. There is no evidence that pancreatic enzymes help reduce the frequency of IRAP, and it is unlikely that biliary dissolution therapy (ursodeoxycholic acid) is effective at reducing attacks in postcholecystectomy patients, especially when noninvasive tests (MRCP/EUS) have ruled out choledocholithiasis.

What is the most effective initial therapy?

For selected patients, endoscopic biliary and/or pancreatic sphincterotomy, as described above. For post-cholecystectomy pain, patients with normal/near normal labsand normal imaging, ERCP is not indicated; antispasmodics or other visceral hypersensitivity therapies need to be pursued.

Listing of usual initial therapeutic options, including guidelines for use, along with expected result of therapy.

See previous discussion on surgical sphincteroplasty.

A listing of a subset of second-line therapies, including guidelines for choosing and using these salvage therapies

Surgical sphincteroplasty is an option but is generally reserved for those with altered upper GI anatomy, making accessibility by ERCP difficult, and in those with recurrent restenosis (generally proven by repeat manometry). Any sphincter intervention, surgical or endoscopic, carries a risk of pancreatitis; so surgery does not avoid the pancreatitis risk.

It is unlikely that surgical sphincter interventions are more effective than ERCP. Efficacy of neuromodulators is unclear. Efficacy of pancreatic enzymes is unclear. Botox around the sphincter (with a temporary pancreatic stent) may be effective in the short term; the logistics of its use as a therapeutic trial are not worked out, as the definition of “response” (given the overlapping placebo effect) is unclear.

For patients with mild symptoms, and those without objective signs of biliary/pancreatic obstruction, conservative therapy is suggested.

Listing of these, including any guidelines for monitoring side effects.

Post-ERCP pancreatitis generally begins within 24 hours, and is associated with typical pancreatic pain and nausea and lipase above three times the normal, with or without supporting imaging, and generally other inflammatory markers (leukocytosis, mild fever). Delayed pancreatitis could occur due to passage or blockage of the temporary pancreatic stent. An abdominal X-ray, including the hemidiaphragms to confirm the spontaneous passage of the temporary stent (which should pass spontaneously more than 85% of the time), is needed at 2 to 4 weeks; and if the stent persists, it needs to be pulled at endoscopy. Stents staying in longer than this period can cause duct damage, some of which can be severe and permanent.

Bleeding (~1%) and perforation (less than 0.5%) can present early or delayed (up to 10-14 days later).

Late restenosis occurs after less than 5% of biliary sphincterotomies but occurs in 20% to 30% of patients after pancreatic sphincterotomy. Therefore, in patients who have undergone pancreatic sphincterotomy, a temporary response for several months, followed by recurrence of symptoms, or cluster of recurrent acute pancreatitis attacks/admissions, may indicate restenosis. Whereas after biliary sphincterotomy, it more likely means a temporary placebo effect has occurred and worn off or, less common, coexisting pancreatic SOD.

How should I monitor the patient with sphincter of Oddi dysfunction?

Other than recurrent pain/pancreatitis, there are no proven long-term proven complications of SOD. Some believe that long-standing SOD could cause other conditions, such as chronic pancreatitis; whereas others feel that when SOD is found in chronic pancreatitis, it is simply secondary to the fibrosing process extending into the sphincter complex (i.e., an effect rather than a cause). As such, no particular monitoring is recommended for patients with unexplained pain.

In those with IRAP, screening for the development of chronic pancreatitis (functional or structural damage) with EUS/MRCP and/or function testing may be reasonable at some point, and perhaps can be repeated after several years to see if there has been progression. However, there is no official recommendation for this procedure.

These patients routinely receive temporary pancreatic duct stenting after sphincterotomy. A “stent X-ray” is generally done at 2 to 4 weeks, at which point patients can often tell if their symptoms are improved. The stents usually spontaneously migrate but if still present, a repeat endoscopy with stent removal is required. Stents should not be left in place for more than 4 weeks. Otherwise, follow-up is on an as needed basis.

If recurrent pains do occur and if severe, another set of liver and pancreatic enzymes is reasonable, especially within 24 to 48 hours of a pain attack. Depending on how long it has been since EGD/EUS/MRCP, these may need repeating. However, beware that once a sphincterotomy is in place, air in the ducts can be mistaken for stones on noninvasive imaging. Rethinking the other diagnostic possibilities is worthwhile. Behavioral medicine and/or psychiatric consultation may be useful in selected patients.

What's the evidence?

Good review of SOD and guidelines for ERCP

Petersen, BT. “Sphincter of Oddi dysfunction, part 2: evidence-based review of the presentations, with "objective" pancreatic findings (types I and II) and of presumptive type III”. Gastrointest Endosc. vol. 59. 2004. pp. 670-87.

Petersen, BT. “An evidence-based review of sphincter of Oddi dysfunction: part I, presentations with "objective" biliary findings (types I and II)”. Gastrointest Endosc. vol. 59. 2004. pp. 525-34.

Cohen, S, Bacon, B, Berlin, J. “National Institutes of Health State-of-the-Science Conference Statement: ERCP for diagnosis and therapy, January 14-16, 2002”. Gastrointest Endosc. vol. 56. 2005. pp. 803-9.

Randomized trial of SOM-directed sphincterotomy

Geenen, JE, Hogan, WJ, Dodds, WJ. “The efficacy of endoscopic sphincterotomy after cholecystectomy in patients with sphincter of Oddi dysfunction”. N Engl J Med. vol. 320. 1989. pp. 82-7.

Toouli, J, Roberts-Thomson, IC, Kellow, J. “Manometry based randomized trial of endoscopic sphincterotomy for sphincter of Oddi dysfunction”. Gut. vol. 46. 2000. pp. 98-102.

Cotton, PB, Durkalski, V, Romagnuolo, J. “Effect of endoscopic sphincterotomy for suspected sphincter of Oddi dysfunction on pain-related disability following cholecystectomy: the EPISOD randomized clinical trial”. JAMA. vol. 311. 2014. pp. 2101-9.

Well-known study showing high accuracy (100% sensitivity and specificity) of scintigraphy for SOD (Sostre et al, “Hopkins protocol/score”), not reproduced by other studies, including sensitivity of 25% to 38% and specificity 86% to 89% (Craig et al); the effect of sphincterotomy on scintigraphy results (Shaffer et al)

Sostre, S, Kalloo, AN, Spiegler, EJ. “A noninvasive test of sphincter of Oddi dysfunction in postcholecystectomy patients: the scintigraphic score”. J Nucl Med. vol. 33. 1992. pp. 1216-22.

Fullarton, GM, Allan, A, Hilditch, T, Murray, WR. “Quantitative 99mTc-DISIDA scanning and endoscopic biliary manometry in sphincter of Oddi dysfunction”. Gut. vol. 29. 1988. pp. 1397-401.

Pineau, BC, Knapple, WL, Spicer, KM. “Cholecystokinin-stimulated mebrofenin (99mTc-Choletec) hepatobiliary scintigraphy in asymptomatic postcholecystectomy individuals: assessment of specificity, interobserver reliability, and reproducibility”. Am J Gastroenterol. vol. 96. 2001. pp. 3106-9.

Farup, PG, Tjora, S. “Sphincter of Oddi dysfunction. Dynamic cholescintigraphy and endoscopic retrograde cholangiopancreatography with papillotomy in diagnosis, treatment, and follow-up study”. Scand J Gastroenterol. vol. 24. 1989. pp. 956-60.

Craig, AG, Peter, D, Saccone, GT. “Scintigraphy versus manometry in patients with suspected biliary sphincter of Oddi dysfunction”. Gut. vol. 52. 2003. pp. 352-7.

Shaffer, EA, Hershfield, NB, Logan, K, Kloiber, R. “Cholescintigraphic detection of functional obstruction of the sphincter of Oddi: effect of papillotomy”. Gastroenterology. vol. 90. 1986. pp. 728-33.

Secretin-stimulated EUS and MRCP to diagnose SOD, with modest results

Catalano, MF, Lahoti, S, Alcocer, E. “Dynamic imaging of the pancreas using real-time endoscopic ultrasonography with secretin stimulation”. Gastrointest Endosc. vol. 48. 1998. pp. 580-7.

Mariani, A, Curioni, S, Zanello, A. “Secretin MRCP and endoscopic pancreatic manometry in the evaluation of sphincter of Oddi function: a comparative pilot study in patients with idiopathic recurrent pancreatitis”. Gastrointest Endos. vol. 58. 2003. pp. 847-52.

Long-term (nonrandomized) outcomes after endoscopic and surgical therapy for SOD, and predictors of response (older age, lack of pancreatitis [Morgan et al.]; older age, pancreatic SOD, lack of gastroparesis, lack of chronic narcotics [Freeman et al.; liver enzymes not predictive]

Park, SH, Watkins, JL, Fogel, EL. “Long-term outcome of endoscopic dual pancreatobiliary sphincterotomy in patients with manometry-documented sphincter of Oddi dysfunction and normal pancreatogram”. Gastrointest Endosc. vol. 57. 2003. pp. 483-91.

Madura, JA, Madura, JA, Sherman, S, Lehman, GA. “Surgical sphincteroplasty in 446 patients”. Arch Surg. vol. 140. 2005. pp. 504-512.

Okolo, PI, Pasricha, PJ, Kalloo, AN. “What are the long-term results of endoscopic pancreatic sphincterotomy?”. Gastrointest Endosc. vol. 52. 2000. pp. 15-9.

Freeman, ML, Gill, M, Overby, C, Cen, YY. “Predictors of outcomes after biliary and pancreatic sphincterotomy for sphincter of Oddi dysfunction”. J Clin Gastroenterol. vol. 41. 2007. pp. 94-102.

Morgan, K, Romagnuolo, J, Adams, D. “Transduodenal sphincteroplasty in the management of sphincter of Oddi dysfunction and pancreas divisum in the modern era”. J Am Coll Surg. vol. 206. 2008. pp. 908-14.

On-going EPISOD sham-controlled trial

Cotton, PB, Durkalski, V, Orrell, KB. “Challenges in planning and initiating a randomized clinical study of Sphincter of Oddi dysfunction”. Gastrointest Enterol. vol. 72. 2010. pp. 986-91.

Durkalski, V, Stewart, W, MacDougall, P. “Measuring episodic abdominal pain and disability in suspected sphincter of Oddi dysfunction”. World J Gastroenterol. vol. 16. 2010. pp. 4416-21.

Preliminary studies of botox injection for SOD, some with high rates of post-ERCP pancreatitis (causing study by Gorelick et al. to be stopped early) but predictive of response (Murray)

Pasricha, PJ, Miskovsky, EP, Kalloo, AN. “Intrasphincteric injection of botulinum toxin for suspected sphincter of Oddi dysfunction”. Gut. vol. 35. 1994. pp. 1319-21.

Wehrmann, T, Seifert, H, Seipp, M. “Endoscopic injection of botulinum toxin for biliary sphincter of Oddi dysfunction”. Endoscopy. vol. 30. 1998. pp. 702-7.

Murray, WR. “Botulinum toxin-induced relaxation of the sphincter of Oddi may select patients with acalculous biliary pain who will benefit from cholecystectomy”. Surg Endosc. vol. 25. 2011 Mar. pp. 813-6.

SOD therapy in IRAP, including randomized trial of stenting by Jacob et al., and systematic review of the literature by Romagnuolo et al.

Jacob, L, Geenen, JE, Catalano, MF. “Prevention of pancreatitis in patients with idiopathic recurrent pancreatitis: a prospective nonblinded randomized study using endoscopic stents”. Endoscopy. vol. 33. 2001. pp. 559-62.

Romagnuolo, J, Guda, N, Freeman, M, Durkalski, V. “Preferred designs, outcomes, and analysis strategies for treatment trials in idiopathic recurrent acute pancreatitis”. Gastrointest Endosc Endosc. vol. 68. 2008. pp. 966-74.

Eversman, D, Fogel, EL, Rusche, M. “Frequency of abnormal pancreatic and biliary sphincter manometry compared with clinical suspicion of sphincter of Oddi dysfunction”. Gastrointest Endosc . vol. 50. 1999. pp. 637-41.

Coyle, WJ, Pineau, BC, Tarnasky, PR. “Evaluation of unexplained acute and acute recurrent pancreatitis using endoscopic retrograde cholangiopancreatography, sphincter of Oddi manometry and endoscopic ultrasound”. Endoscopy. vol. 34. 2002. pp. 617-23.

Kaw, M, Brodmerkel, GJ. “ERCP, biliary crystal analysis, and sphincter of Oddi manometry in idiopathic recurrent pancreatitis”. Gastrointest Endosc. vol. 55. 2002. pp. 157-62.

Benefits of pancreatic stents in ERCP for SOD, and the harm and potential for stent-related damage

Singh, P, Das, A, Isenberg, G. “Does prophylactic stent placement reduce the risk of post-ERCP acute pancreatic? A meta-analysis of controlled trials”. Gastrointest Endosc. vol. 60. 2004. pp. 544-50.

Sherman, S, Hawes, RH, Savides, TJ. “Stent-induced pancreatic ductal and parenchymal changes: correlation of endoscopic ultrasound with ERCP”. Gastrointest Endosc. vol. 44. 1996. pp. 276-82.

Gorelick, A, Barnett, J, Chey, W. “Botulinum toxin injection after biliary sphincterotomy”. Endoscopy. vol. 36. 2004. pp. 170-3.

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