Wednesday, September 19, 2007

Sphincter of Oddi Dysfunction
Emerg Med 37(3):14-17, 2005
http://www.emedmag.com/html/pre/gic/consults/031505.asp

By John Baillie, MB, ChB, FRCP
Dr. Baillie is a professor of medicine in the division of gastroenterology, department of medicine, at Duke University Medical Center in Durham, North Carolina.

The author discusses clinical manifestations of functional problems with the biliary and pancreatic sphincters and the specialized techniques used to treat them.

The sphincter of Oddi is a valve comprised of circular muscle that controls the opening and closing of the bile duct within the duodenal papilla (ampulla of Vater). Its resting state is contracted—that is, closed. When neural or humoral signals cause it to relax, bile is released into the duodenum to assist in the digestion of dietary fat. There is a separate but less well-defined sphincter controlling the release of pancreatic juice. Typically, ablation of the sphincter of Oddi by sphincterotomy does not destroy the pancreatic sphincter.

Sphincter of Oddi dysfunction encompasses various conditions in which the biliary or pancreatic sphincter is considered to be malfunctioning. This article will focus principally on biliary sphincter dysfunction.

What is sphincter of Oddi dysfunction (SOD)?
The term sphincter of Oddi dysfunction was first used in a paper published in the New England Journal of Medicine in 1989 by Joseph Geenen, Walter Hogan, and colleagues. Because their work was done in part in Milwaukee, Wisconsin, their proposed classification of SOD became known as the Milwaukee classification. Geenen and Hogan were trying to make sense of the underlying pathology in a heterogeneous group of patients with biliary-type pain following cholecystectomy. They developed their classification system based on the following criteria: typical biliary pain; liver function test (LFT) abnormalities (specifically, elevations in serum transaminase levels of 1.5 times normal or higher on two occasions related to pain, with resolution between attacks); dilatation of the common bile duct of 12 mm or more; and delayed drainage of contrast medium from the biliary tree. Over time, the last criterion was repeatedly shown to be an unreliable sign of SOD and was dropped.

Using these criteria, Geenen, Hogan, and colleagues divided SOD patients into three types (see table below). Type I patients exhibit all three criteria. They constitute a subgroup of post-cholecystectomy patients with a mechanical outlet obstruction to biliary flow (papillary stenosis). About 95% of type I patients are cured by endoscopic biliary sphincterotomy (EBS). Biliary pressure measurement does not affect the outcome and is not indicated in these patients.
_____________________________________

Milwaukee Classification of Sphincter of Oddi Dysfunction

Type of SOD................................I II III

Biliary pain.................................+ + +

Elevated LFTs x 2.........................+ +/-(*) -

Bile duct dilatation > 12 mm.............+ -/+(*) -

(*) one or the other, but not both
______________________________________

Type II patients have typical biliary pain and either abnormal liver serology or dilatation of the bile duct, but not both. Type II patients with abnormal sphincter of Oddi manometry have an 80% or better chance of improvement following EBS. Those whose pressures are normal benefit only 30% of the time. For this reason, it is strongly recommended that suspected type II patients undergo biliary manometry.

Type III patients have typical biliary pain alone. These patients have the least likelihood of benefiting from EBS. In most centers, the improvement rate is in the range of 30% to 40% if sphincter of Oddi manometry is positive, but less than 20% if it is negative. These patients also have the highest complication rate from endoscopic retrograde cholangiopancreatography (ERCP). Type III patients should never have EBS for suspected SOD without prior manometry showing elevated sphincter of Oddi pressures.

Does this mean that EBS should not be performed empirically for biliary pain?
Exactly. As a risk management strategy, endoscopists would do well to steer clear of type III SOD patients. They have the highest risk of post-ERCP pancreatitis and the lowest yield in terms of long-term benefit from intervention. The guidelines of the American Society for Gastrointestinal Endoscopy have clearly stated for more than a decade that ERCP "is generally not indicated" in the investigation of pain syndromes without other evidence of biliary obstruction. With the literature now quite clear about the significant risks and limited benefits of ERCP in this setting, it is difficult to defend oneself medicolegally against severe pancreatitis complicating such procedures.

In type III patients, the extrahepatic bile duct is not dilated, making cannulation difficult. Prolonged unsuccessful instrumentation of the duodenal papilla in an attempt to obtain a cholangiogram makes pancreatitis likely. Sometimes damage is done with a needle-knife catheter, which is used to make a blind cut into the duodenal papilla to expose the bile duct. Needle-knife papillotomy is a dangerous procedure in this setting and should be avoided.

What is sphincter of Oddi manometry and where can patients have it done?
Sphincter of Oddi manometry is a specialized technique for measuring biliary and sometimes pancreatic sphincter pressure. Given the cost of the equipment and the technical difficulty of performing the procedure, it is typically limited to tertiary referral centers where hepatobiliary and pancreatic disorders are managed. At my institution, we use general anesthesia in about one-third of these procedures. Because many SOD patients are habituated to narcotic analgesics and benzodiazepines, they can be very difficult to sedate using standard techniques.

In the early days, sphincter of Oddi manometry was performed using a water-perfusion pump system. Most centers now use solid-state pressure transducers that are read and interpreted by specialized computer software. Details regarding the test results are beyond the scope of this article, but we look for sustained elevations (lasting 20 to 30 seconds or more) in sphincter pressure in multiple leads of more than 40 mm Hg. Certain drugs, such as morphine and anticholinergics, must be avoided during ERCP for sphincter of Oddi manometry because they can affect the pressure readings.

We do not offer direct-to-procedure access for sphincter of Oddi manometry. Suspected SOD patients need to be evaluated in a specialist clinic first because many of them do not fit the criteria for this diagnosis. At my institution, only about a third of patients referred as having type III SOD end up being offered ERCP with sphincter of Oddi manometry. The remainder are thought to have some variant of chronic functional abdominal pain, gastroesophageal reflux disease, chest wall pain syndrome (from costochondritis or fibromyalgia, for example), or orthopedic pain.

Referring physicians should be careful to avoid promising suspected SOD patients that certain procedures will be done. These patients typically arrive with unrealistic expectations of what can be done for them and are often angry and disappointed when told that they do not fit the criteria for SOD.

Outside the United States, SOD is considered an American disease. Sphincter of Oddi manometry is rarely offered in Europe, Asia, or Africa. Is SOD really just a myth?
That is a difficult question to answer. Type I SOD (papillary stenosis) certainly exists, and it is the most satisfying to treat. We never see it in referral centers because it can be cured in the hospital or clinic setting with EBS. Most patients diagnosed as having type III SOD do not have a demonstrable sphincter abnormality. Unfortunately, they comprise 80% to 90% of the patients referred for work-up. Many of them are anxious, depressed, frustrated, and angry. They are best assessed in a specialist clinic by physicians and other staff who have experience in investigating and managing this condition.

In my experience, type II patients present the greatest challenge. When one returns to the original Milwaukee criteria, it is clear that the LFT abnormalities have to normalize between attacks and that bile duct dilatation is defined as 12 mm or more. It is not uncommon, however, to see patients referred as having possible type II SOD who have mild elevations in LFTs (including alkaline phosphatase levels) that never normalize or enlargement of the bile duct that is less than 12 mm. (The upper limit of normal is generally considered to be 7 mm.)
Patients with persistently abnormal LFTs are usually obese and often have hepatic steatosis (fatty liver) on biopsy. Chronic drug-related LFT elevations are another source of confusion. It is often hard to interpret mild dilatation of the extrahepatic bile duct. On its own, this finding has little clinical significance. The duct could contain a stone or perhaps a small distal tumor that is causing the enlargement. If there is sufficient cause for concern, endoscopic ultrasound is a noninvasive way to explore this possibility. Magnetic resonance cholangiography used to be relatively insensitive for detecting small biliary stones, but this is no longer the case. For many patients in this setting, using another form of imaging to avoid ERCP makes sense.

Undoubtedly, some patients with idiopathic acute recurrent pancreatitis have a hypertensive pancreatic sphincter. For these individuals, pancreatic sphincterotomy may cure the problem. Pancreatic sphincter dysfunction is a rare diagnosis that requires specialist investigation and management.

Sphincterotomy seems like a blunt tool to use to manage a fairly subtle abnormality. What progress has been made in the pharmacologic management of SOD?
Since the late 1970s, when Staritz in Germany claimed success using topical nitrates, endoscopists have been looking for a local or systemic agent to relax the sphincter of Oddi. So far, the results have been disappointing. There is some rationale for using nitrates, since nitric oxide is an important neurotransmitter regulating sphincter of Oddi tone. Calcium channel blockers, such as nifedipine, have also been tried, with limited success.

Kalloo and others have tried inhibiting sphincter of Oddi contraction using a local injection of botulinum toxin into the duodenal papilla. The initial data were encouraging, but these results have not been confirmed by larger studies. It now appears that such an injection may provoke a chronic inflammatory response that could actually cause papillary stenosis over time. Other pharmacologic agents, including neurotoxic venoms, are currently being evaluated for treating SOD.

What about balloon dilation of the sphincter? Is this worth a trial in SOD?
The U.S. multicenter trial of endoscopic sphincterotomy versus EBS for management of bile duct stones, recently published in Gastroenterology, showed that EBS carries a very significant risk of procedure-related pancreatitis. Most experts believe that the risk of EBS is even greater in SOD patients, who already have a sensitive sphincter. In my opinion, SOD patients should never be managed with EBS or a trial of biliary stenting.

Is there any way to reduce the risk of post-ERCP pancreatitis in SOD patients?
Yes. There are good data now available that prophylactic stenting of the pancreatic duct orifice, using small-caliber, unflanged, single-pigtail stents, greatly reduces the risk of post-ERCP pancreatitis and appears to virtually abolish the risk of severe, necrotizing pancreatitis. Whenever possible, we place a 6- to 8-cm long, #3 French pancreatic stent when performing sphincter of Oddi manometry in potential SOD patients, regardless of whether sphincterotomy is performed. The majority of these stents spontaneously migrate out of the pancreas within days after the procedure. We also recommend prophylactic stenting of the pancreatic duct whenever there has been repeated or otherwise traumatic instrumentation of the papilla during ERCP.

What progress has been made toward a noninvasive radiologic test for SOD?
This is the holy grail of ERCP. Most endoscopists who perform sphincter of Oddi manometry would be delighted never to have to do another one. Unfortunately, no noninvasive test has clearly emerged as a sensitive and specific alternative. A number of studies of so-called gated radionuclide biliary scans have claimed to show good correlation with sphincter of Oddi manometry and the results of sphincterotomy. However, none has withstood the test of time. Magnetic resonance cholangiography-based dynamic testing is currently being evaluated. At present, ERCP with sphincter of Oddi manometry remains the gold standard for diagnosing SOD.

Suggested Reading
  • Eversman D, et al.: Frequency of abnormal pancreatic and biliary sphincter manometry compared with clinical suspicion of sphincter of Oddi dysfunction. Gastrointest Endosc 50(5):637, 1999.
  • Freeman ML: Role of pancreatic stents in the prevention of post-ERCP pancreatitis. JOP 5(5):322, 2004.
  • Geenen JE, et al.: The efficacy of endoscopic sphincterotomy after cholecystectomy in patients with sphincter of Oddi dysfunction. N Engl J Med 320(2):82, 1989.
  • Rashdan A, et al.: Improved stent characteristics for prophylaxis of post-ERCP pancreatitis. Clin Gastroenterol Hepatol 2(4):322, 2004.
  • Rosenblatt ML, et al.: Comparison of sphincter of Oddi manometry, fatty meal sonography and hepatobiliary scintigraphy in the diagnosis of sphincter of Oddi dysfunction. Gastrointest Endosc 54(6):697, 2001.

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Digestive Diseases Library

Saturday, July 21, 2007

Sphincter of Oddi Dysfunction: Diagnosis and Treatment

JOP. J Pancreas (Online) 2001; 2(6):382-400.
Sphincter of Oddi Dysfunction: Diagnosis and Treatment
http://www.joplink.net/prev/200111/04.html

Stuart Sherman, Glen A Lehman


Division of Gastroenterology/Hepatology, Department of Medicine, Indiana University Medical Center. Indianapolis, IN, USA


Introduction

Since its original description by Ruggero Oddi in 1887, the sphincter of Oddi (SO) has been the subject of much study and controversy. Its very existence as a distinct anatomic or physiologic entity has been disputed. Hence, it is not surprising that the clinical syndrome of sphincter of Oddi dysfunction (SOD) and its therapy are controversial areas [1]. Nevertheless, SOD is commonly diagnosed and treated by physicians. This section reviews the anatomy and physiology of the SO, clinical presentations, and methods to diagnose and treat SOD.

Definition

SOD refers to an abnormality of SO contractility. It is a benign, noncalculous obstruction to flow of bile or pancreatic juice through the pancreaticobiliary junction, I.e., the sphincter of Oddi. SOD may be manifested clinically by pancreaticobiliary pain, pancreatitis, or deranged liver function tests. It is actually made up of two entities. SO dyskinesia refers to a primary motor abnormality of the SO which may result in a hypotonic sphincter but more commonly, a hypertonic sphincter. In contrast, SO stenosis refers to a structural alteration of the sphincter, probably from an inflammatory process with subsequent fibrosis. Because it is often impossible to distinguish patients with SO dyskinesia from those with SO stenosis, the term SOD has been used to incorporate both groups of patients. In an attempt to deal with this overlap in etiology, and also to determine the appropriate utilization of SO manometry (SOM), a clinical classification system has been developed for patients with suspected SOD [2] (Hogan-Geenen SOD classification system; Table 1) based on clinical history, laboratory results, and ERCP findings.

Table 1. Hogan-Geenen sphincter of Oddi classification system related to the frequency of abnormal sphincter of Oddi manometry and pain relief by biliary sphincterotomy.

Patient group classifications...Approximate....Probability of pain...............Manometry before
...............................................frequency of.....relief by sphincterotomy.....sphincter ablation
...............................................abnormal..........if manometry:
...............................................sphincter
................................................manometry
Biliary I

Patients with biliary-type
pain, abnormal SGOT or...........................................Abnormal Normal
alkaline phosphatase >2 x normal........75-95%..................90-95%......90-95%..........Unnecessary
documented on two or more
ERCP contrast from the biliary
tree >45 minutes, and occasions,
delayed drainage of dilated
CBD >12 mm diameter.

Biliary II

Patients with biliary-
type pain, but only.....................55-65%.....................85%.............35%................Highly
one or two of the criteria.................................................................................recommended
listed above.

Biliary III

Patients with only.......................25-60%................55-65%.........<10%...............mandatory


A variety of less accurate terms are listed in the medical literature to describe this entity such as papillary stenosis, Ampullary stenosis, biliary dyskinesia, and post-Cholecystectomy syndrome (even though SOD may occur with the gallbladder intact).

Anatomy, Physiology and Pathophysiology

The sphincter of Oddi is a small complex of smooth muscles surrounding the terminal common bile duct, main (ventral) pancreatic duct (of Wirsung), and the common channel (ampulla of Vater), when present. It has both circular and figure-8 components. The high-pressure zone generated by the sphincter is variably 4-10 mm. in length. Its role is to regulate bile and pancreatic exocrine juice flow and to prevent duodenum-to-duct reflux (I.e., maintain sterile Intraductal environment). The SO possesses both a variable basal pressure and phasic contractile activity. The former appears to be the predominant mechanism, regulating outflow of pancreaticobiliary secretion into the intestine. Although phasic SO contractions may aid in regulating bile and pancreatic juice flow, their primary role appears to be maintaining a sterile Intraductal milieu. Sphincter regulation is under both neural and hormonal control. Phasic wave activity of the sphincter is closely tied to the migrating motor complex (MMC) of the duodenum. Innervation of the bile duct does not appear to be essential as sphincter function has been reported to be preserved following liver transplantation [3]. Although regulatory processes vary among species, cholecystokinin and secretin appear to be most important in causing sphincter relaxation while nonadrenergic, noncholinergic neurons which at least in part transmit vasoactive intestinal peptide (VIP) and nitric oxide also relax the sphincter [4]. The role of Cholecystectomy in altering these neural pathways needs further definition. Luman and colleagues [5] reported that Cholecystectomy, at least in the short-term, suppresses the normal inhibitory effect of pharmacological doses of CCK on the sphincter of Oddi. However, the mechanism of this effect is unknown.

Wedge specimens of the SO obtained at surgical sphincteroplasty from SOD patients, show evidence of inflammation, muscular hypertrophy, fibrosis or adenomyosis within the papillary zone in approximately 60% of patients [6]. In the remaining 40% with normal histology, a motor disorder is suggested. Less commonly, infections with Cytomegalovirus or Cryptosporidium, as may occur in AIDS patients, or Strongyloides have caused SOD.

How does SOD cause pain? From a theoretical point of view, abnormalities of the SO can give rise to pain by, impeding the flow of bile and pancreatic juice resulting in ductal hypertension, ischemia arising from spastic contractions, and "hypersensitivity" of the papilla. Although unproven, these mechanisms may act alone or in concert to explain the genesis of pain.

Epidemiology

SOD may occur in pediatric or adult patients of any age; however, patients with SOD are typically middle-aged females [7]. A survey on functional gastrointestinal disorders confirmed that SOD affects females more frequently than males and indicated a high association with work absenteeism, disability, and healthcare use [8]. Although SOD most commonly occurs after cholecystectomy, it may be present with the gallbladder in situ.

The frequency of manometrically documented SOD in patients prior to cholecystectomy has received limited study. Guelrud and colleagues [9] studied 121 patients with symptomatic gallstones and a normal common bile duct diameter (by transcutaneous ultrasound) by SOM prior to cholecystectomy. An elevated basal sphincter pressure was found in 14 patients (11.6%). SOD was diagnosed in 4.1% of patients with a normal serum alkaline phosphatase (4 of 96) and in 40% with an elevated serum alkaline phosphatase (10 of 25). Ruffolo et al. evaluated 81 patients with symptoms suggestive of biliary disease but normal ERCP and no gallbladder stones on transcutaneous ultrasound by scintigraphic gallbladder ejection fraction and endoscopic SOM [10]. Fifty-three percent of patients had SOD and 49% had an abnormal gallbladder ejection fraction. SOD occurred with a similar frequency in patients with an abnormal gallbladder ejection fraction (50%) and a normal ejection fraction (57%).

Post-cholecystectomy pain resembling the patient's preoperative biliary colic occurs in at least 10-20% of patients [11]. The frequency of diagnosing SOD in reported series varies considerably with the patient selection criteria, the definition of SOD utilized, and the diagnostic tools employed. In a British report, Sphincter of Oddi dysfunction was diagnosed in 9% of 451 consecutive patients being evaluated for post cholecystectomy pain [12]. Roberts-Thomson evaluated 431 similar patients and found SOD in 11%. In a subpopulation of such patients with a normal ERCP (except dilated ducts in 28%) and recurrent pain of more than 3-month duration, SOD was diagnosed in 68% [13]. Sherman and colleagues used SOM to evaluate 115 patients with pancreaticobiliary pain with and without liver function test abnormalities [14]. Patients with bile duct stones and tumors were excluded from analysis. Fifty-nine of 115 patients (51%) had an abnormal basal sphincter of Oddi pressure greater than 40 mmHg. These patients were further categorized by the Hogan-Geenen SOD classification system (Table 1). The frequency of abnormal manometry was 86%, 55% and 28%, for Type I, II and III patients respectively. These abnormal manometric frequencies are very similar to those reported by others for Type I and Type II patients [15, 16]. In Type III patients, the finding of an abnormal basal sphincter pressure has varied from 12-55% [17]. As noted, patient selection factors may be one explanation for this great variability.

SOD can involve abnormalities in either the biliary sphincter, pancreatic sphincter, or both. The true frequency of SOD would then depend on whether one or both sphincters were studied. To fully assess the sphincter by SOM both the bile duct and pancreatic ducts must be evaluated. In a series [18] of 360 patients with pancreaticobiliary pain, 19% had abnormal pancreatic sphincter basal pressure alone, 11% had abnormal biliary basal sphincter pressure alone, and in 31%, the basal pressure was abnormal for both sphincters (overall frequency of SOD was 61%). Among the 214 patients labeled Type III, 17%, 11%, and 31% had elevated basal sphincter pressure in the pancreatic sphincter alone, biliary sphincter alone, or both the biliary and pancreatic sphincters respectively (overall frequency of SOD 59%). In the 123 patients labeled Type II, SOD was diagnosed in 65%; 22%, 11%, and 32% had the elevated basal sphincter pressure in the pancreatic sphincter only, biliary sphincter only, or both sphincters respectively.

Dysfunction may occur in the pancreatic duct portion of the SO and cause recurrent pancreatitis and pancreatic-type pain. Although a pancreatic SOD classification system has been developed (similar to the biliary SOD classification system), it has not been widely utilized [18]. Manometrically documented SOD has been reported in 15 to 72% of patients with recurrent pancreatitis, previously labeled as idiopathic [17, 18, 19].

Clinical Presentation

Abdominal pain is the most common presenting symptom of patients with SOD. The pain is usually epigastric or right upper quadrant, may be disabling, and lasts for 30 minutes to several hours. In some patients the pain is continuous with episodic exacerbations. It may radiate to the back or shoulder and be accompanied by nausea and vomiting. Food or narcotics may precipitate the pain. The pain may begin several years after a cholecystectomy was performed for a gallbladder dysmotility or stone disease and is similar in character to the pain leading to the cholecystectomy. Alternatively, patients may have continued pain that was not relieved by a cholecystectomy. Jaundice, fever, or chills are rarely observed. The Rome II diagnostic criteria [7] for SOD are episodes of severe steady pain located in the epigastrium and right upper quadrant, and all of the following: 1) symptom episodes last 30 minutes or more with pain-free intervals; 2) symptoms have occurred on one or more occasions in the previous 12 months; 3) the pain is steady and interrupts daily activities or requires consultation with a physician; and 4) there is no evidence of structural abnormalities to explain the symptoms. Physical examination is characterized by the paucity of any abnormal findings. The most common physical finding is mild, nonspecific abdominal tenderness. The pain is not relieved by trial medications for acid-peptic disease or irritable bowel syndrome. Laboratory abnormalities consisting of transient elevation of liver function tests, typically during episodes of pain, are present in less than 50% of patients. After initial evaluation, patients are commonly categorized according to the Hogan-Geenen SOD classification system (Table 1). Patients with SOD may present with typical pancreatic pain (epigastric and/or left upper quadrant radiating to the back) and recurrent pancreatitis.

SOD may exist in the presence of an intact biliary tract with the gallbladder in situ [20]. As the symptoms of SO or gallbladder dysfunction cannot be readily separated, the diagnosis of SOD is commonly made after cholecystectomy or less frequently after proper investigations have excluded gallbladder abnormalities [7].

Clinical Evaluation

The diagnostic approach to suspected SOD may be influenced by the presence of key clinical features. However, the clinical manifestations of functional abnormalities of the SO may not always be easily distinguishable from those caused by organic ones (e.g., common bile duct stones) or other functional non-pancreaticobiliary disorders (e.g., irritable bowel syndrome).

General Initial Evaluation

Evaluation of patients with suspected SOD (i.e., patients with upper abdominal pain with characteristics suggestive of a pancreatobiliary origin) should be initiated with standard serum liver chemistries, serum amylase and/or lipase, abdominal ultrasonography and/or computerized axial tomography (CAT) scans. The serum enzyme studies should be drawn during bouts of pain, if possible. Mild elevations (<2>6 mm in the pancreatic head and >5 mm in the body) and delayed contrast drainage time (³ 9 min in the prone position) may give indirect evidence for the presence of SOD.


Sphincter of Oddi Manometry

The most definitive development in our understanding of the pressure dynamics of the SO came with the advent of SOM. SOM is the only available method to measure SO motor activity directly. Although SOM can be performed intraoperatively and percutaneously, it is most commonly done in the ERCP setting. SOM is considered by most authorities to be the gold standard for evaluating patients for sphincter dysfunction [38, 39]. The use of manometry to detect motility disorders of the sphincter of Oddi is similar to its use in other parts of the gastrointestinal tract. Unlike other areas of the gut, SOM is more technically demanding and hazardous. Questions remain as to whether these short-term observations (2-10 minute recordings per pull-through) reflect the "24-hour pathophysiology" of the sphincter. Despite some problems, SOM is gaining more widespread clinical application.

SOM Technique and Indications

Sphincter of Oddi manometry is usually performed at the time of ERCP. All drugs which relax (anticholinergics, nitrates, calcium channel blockers, and glucagon) or stimulate (narcotics or cholinergic agents) the sphincter should be avoided for at least 8-12 hours prior to manometry and during the manometric session. The current data indicate that benzodiazepines do not affect the sphincter pressure and therefore are acceptable sedation for SOM. Recent data suggested that meperidine, at a dose of £ 1 mg/kg, does not affect the basal sphincter pressure (although it did affect the phasic wave characteristics) [40]. Since the basal sphincter pressure is generally the only manometric criterion used to diagnose sphincter of Oddi dysfunction and determine therapy, it was suggested that meperidine could be used to facilitate conscious sedation for manometry. Propofol is becoming increasingly utilized for SOM [41]. If glucagon must be used to achieve cannulation, an 8-10 minute (at least) waiting period is required to restore the sphincter to its basal condition.

Five-French catheters should be used, since virtually all standards have been established with these catheters. Triple-lumen catheters are state of the art and are available from several manufacturers. A variety of catheter types can be utilized. Catheters with a long intraductal tip may help secure the catheter within the bile duct, but such a long nose is commonly a hindrance if pancreatic manometry is desired. Over-the-wire (monorail) catheters can be passed after first securing one's position within the duct with a guidewire. Some triple-lumen catheters will accommodate a 0.018-inch diameter guidewire passed through the entire length of the catheter and can be used to facilitate cannulation or maintain position in the duct. Guidewire-tipped catheters are being evaluated. Aspiration catheters in which one recording port is sacrificed to permit both end- and side-hole aspiration of intraductal juice and the perfusate are highly recommended for pancreatic manometry [42]. Most centers prefer to perfuse the catheters at 0.25 mL/channel using a minimally compliant pneumohydraulic capillary infusion system. Lower perfusion rates will give accurate basal sphincter pressures, but will not give accurate phasic wave information. The perfusate is generally distilled water, although physiologic saline needs further evaluation. The latter may crystallize in the capillary tubing of perfusion pumps and must be flushed out frequently.

Sphincter of Oddi manometry requires selective cannulation of the bile duct and/or pancreatic duct. The duct entered can be identified by gently aspirating on any port. The appearance of yellow-colored fluid in the endoscopic view indicates entry into the bile duct. Clear aspirate indicates that the pancreatic duct was entered. It is preferable to obtain a cholangiogram and/or pancreatogram prior to performing SOM as certain findings (e.g. common bile duct stone) may obviate the need for SOM. This can simply be done by injecting contrast through one of the perfusion ports. Blaut and colleagues [43] have recently shown that injection of contrast into the biliary tree prior to SOM does not significantly alter sphincter pressure characteristics. Similar evaluation of the pancreatic sphincter after contrast injection has not been reported. One must be certain that the manometry catheter is not impacted against the wall of the duct in order to assure accurate pressure measurements. Once deep cannulation is achieved and the patient acceptably sedated, the catheter is withdrawn across the sphincter at 1-2 mm intervals by standard station pull-through technique. Ideally, both the pancreatic and bile ducts should be studied. Current data indicate that an abnormal basal sphincter pressure may be confined to one side of the sphincter in 35-65% of patients with abnormal manometry [18, 44, 45, 46, 47, 48]. Thus, one sphincter may be dysfunctional whereas the other normal. Raddawi and colleagues [44] reported that an abnormal basal sphincter was more likely to be confined to the pancreatic duct segment in patients with pancreatitis and to the bile duct segment in patients with biliary-type pain and elevated liver function tests.

Abnormalities of the basal sphincter pressure should ideally be observed for at least 30 seconds in each lead and be seen on two or more separate pull-throughs. From a practical clinical standpoint, we settle for one pull through (from each duct) if the readings are clearly normal or abnormal. During standard station pull-through technique, it is necessary to establish good communication between the endoscopist and the manometrist who is reading the tracing as it rolls off the recorder. This permits optimal positioning of the catheter in order to achieve interpretable tracings. Once the baseline study is done, agents to relax or stimulate the sphincter can be given (example: cholecystokinin) and manometric and/or pain response monitored. The value of these provocative maneuvers for everyday use needs further study before widespread application is recommended.



Criteria for interpretation of a SO tracing are relatively standard; however, they may vary somewhat from center to center. Some areas where there may be disagreement in interpretation include the required duration of basal SO pressure elevation, the number of leads in which basal pressure elevation is required, and the role of averaging pressures from the three (or two in an aspirating catheter) recording ports [2]. Our recommended method for reading the manometry tracings is to first define the "zero" duodenal baseline before and after the pull-through. Alternatively, intraduodenal pressure can be continuously recorded from a separate intraduodenal catheter attached to the endoscope. Identify the highest basal pressure (Figure 1) that is sustained for a least 30 seconds (and preferably over one minute). Take the four lowest amplitude points in that zone and take the mean of these readings as the basal sphincter pressure for that lead for that pull-through. Average the basal sphincter pressure for all interpretable observations and take this as the final basal sphincter pressure. The amplitude of phasic wave contractions is measured from the beginning of the slope of the pressure increase from the basal pressure to the peak of the contraction wave. Four representative waves are taken for each lead and the mean pressure determined. The number of phasic waves per minute and the duration of the phasic waves can also be determined. Most authorities read only the basal sphincter pressure as an indicator of pathology of the SO. However, data from Kalloo and colleagues [49] suggest that intrabiliary pressure (which is easier to measure than SO pressure) correlates with SO basal pressure. In this study, intrabiliary pressure was significantly higher in patients with SOD than those with normal SO pressure (20 vs. 10 mmHg; P<0.01).>35 mmHg
Basal ductal pressure.................>13 mmHg
Phasic contractions
- Amplitude..................................>220 mmHg
- Duration.....................................>8 sec
- Frequency.................................>10/min

Note: Values were obtained by adding 3 standard deviations to the mean (means were obtained by averaging the results on 2-3 station pull-throughs). Data combine pancreatic and biliary studies.
* Basal pressures determined by: 1) reading the peak basal pressure (i.e., highest single lead as obtained using a 3 lumen catheter); 2) obtaining the mean of these peak pressures from multiple station pull-throughs.
Adapted from reference [50]

Several studies have indicated that pancreatitis is the most common major complication after SOM [42, 51, 52]. Using standard perfused catheters, pancreatitis rates as high as 31% have been reported. Such high complication rates have initially limited more widespread use of SOM. These data also emphasize that manometric evaluation of the pancreatic duct, particularly in patients with chronic pancreatitis, is associated with a high complication rate. Rolny and associates reported an 11% incidence of pancreatitis following pancreatic duct manometry [51]. Twenty-six percent of chronic pancreatitis patients undergoing SOM developed pancreatitis. A variety of methods to decrease the incidence of post-manometry pancreatitis have been proposed. These include: 1) use of an aspiration catheter; 2) gravity drainage of the pancreatic duct after manometry; 3) decrease the perfusion rate to 0.05-0.1 mL/lumen/minute; 4) limit pancreatic duct manometry time to less than 2 minutes (or avoid pancreatic manometry); 5) use the microtransducer (non-perfused) system [17]. In a prospective randomized study, Sherman and colleagues found that the aspirating catheter (this catheter allows for aspiration of the perfused fluid from end and side holes while accurately recording pressure from the two remaining sideports) reduced the frequency of pancreatic duct manometry-induced pancreatitis from 31 to 4% [42]. The reduction in pancreatitis with use of this catheter in the pancreatic duct and the very low incidence of pancreatitis after bile duct manometry lend support to the notion that increased pancreatic duct hydrostatic pressure is a major cause of this complication. Thus, when we study the pancreatic duct sphincter by SOM, we routinely aspirate pancreatic juice.

SOM is recommended in patients with idiopathic pancreatitis or unexplained disabling pancreaticobiliary pain with or without hepatic enzyme abnormalities. An attempt is made to study both sphincters, but clinical decisions can be made when the first sphincter evaluated is abnormal. An ERCP is usually performed (if an adequate study is not available) immediately before the SOM to exclude other potential causes for the patient's symptoms. Indications for the use of SOM have also been developed according to the Hogan-Geenen SOD classification system (Table 1). In Type I patients, there is a general consensus that a structural disorder of the sphincter (i.e., sphincter stenosis) exists. Although SOM may be useful in documenting SOD, it is not an essential diagnostic study prior to endoscopic or surgical sphincter ablation. Such patients uniformly benefit from sphincter ablation regardless of the SOM results (see below). Type II patients demonstrate SO motor dysfunction in 50 to 65% of cases. In this group of patients, SOM is highly recommended as the results of the study predict outcome from sphincter ablation. Type III patients have pancreaticobiliary pain without other objective evidence of sphincter outflow obstruction. SOM is mandatory to confirm the presence of SOD. Although not well studied, it appears that the results of SOM may predict outcome from sphincter ablation in these patients.

Stent Trial as Diagnostic Test

Placement of a pancreatic or biliary stent on a trial basis in hope of achieving pain relief and predicting the response to more definitive therapy, i.e., sphincter ablation, has received only limited application. Pancreatic stent trials, especially in patients with normal pancreatic ducts, are strongly discouraged as serious ductal and parenchymal injury may occur if stents are left in place for more than a few days [53]. Goff reported a biliary stent trial in 21 Type II and III SOD patients with normal biliary manometry [54]. Seven-French stents were left in place for at least 2 months if symptoms resolved and removed sooner if they were judged ineffective. Relief of pain with the stent was predictive of long term pain relief after biliary sphincterotomy. Unfortunately, 38% of the patients developed pancreatitis (14% were graded severe) following stent placement. Because of this high rate of complications, biliary stent trials are strongly discouraged. Rolny and colleagues also reported a series of bile duct stent placement as predictor of outcome following endoscopic sphincterotomy in 23 post-cholecystectomy patients (7 Type II and 16 Type III) [55]. Similar to the study by Goff [54], resolution of pain during at least 12 weeks of stenting predicted a favorable outcome from sphincterotomy irrespective of sphincter of Oddi pressure. In this series there were no complications related to stent placement.


Therapy for SOD

The therapeutic approach in patients with SOD is aimed at reducing the resistance caused by the sphincter of Oddi to the flow of bile and/or pancreatic juice [7]. The therapy of SOD is evolving. Historically, most emphasis has been placed on definitive intervention, i.e., surgical sphincteroplasty or endoscopic sphincterotomy. This appears appropriate for patients with high-grade obstruction (Type I as per Hogan-Geenen criteria). In patients with lesser degrees of obstruction, the clinician must carefully weigh the risks and benefits before recommending invasive therapy. Most reports indicate that SOD patients have a complication rate from endoscopic sphincterotomy of at least twice that of patients with ductal stones.

Medical Therapy Medical therapy for documented or suspected SOD has received only limited study. Because the SO is a smooth muscle structure, it is reasonable to assume that drugs that relax smooth muscle might be an effective treatment for SOD. Sublingual nifedipine and nitrates have been shown to reduce the basal sphincter pressures in asymptomatic volunteers and symptomatic patients with SOD [1, 56]. Khuroo and colleagues [57] evaluated the clinical benefit of nifedipine in a placebo controlled crossover trial. Twenty-one of 28 patients (75%) with manometrically documented SOD had a reduction in pain scores, emergency room visits and use of oral analgesics during short-term follow-up. In a similar study, Sand et al. [58] found that 9 of 12 (75%) Type II SOD (suspected; SOM was not done) patients improved with nifedipine. Although medical therapy may be an attractive initial approach in patients with SOD, several drawbacks exist [1]. First, medication side-effects may be seen in up to one-third of patients. Second, smooth muscle relaxants are unlikely to be of any benefit in patients with the structural form of SOD (i.e., SO stenosis) and the response is incomplete in patients with a primary motor abnormality of the SO (i.e., SO dyskinesia). Finally, long-term outcome from medical therapy has not been reported. Nevertheless, because of the "relative safety" of medical therapy and the benign (though painful) character of SOD, this approach should be considered in all Type III and less severely symptomatic Type II SOD patients before considering more aggressive sphincter ablation therapy. Guelrud and colleagues have demonstrated [59] that transcutaneous electrical nerve stimulation (TENS) lowers the basal sphincter pressure in SOD patients by a mean of 38% (but unfortunately, generally not into the normal range). This stimulation was associated with an increase in serum VIP levels. Electroacupuncture applied at acupoint GB 34 (a specific acupoint that affects the hepatobiliary system) was shown to relax the sphincter of Oddi in association with increased plasma CCK levels [60]. Its role in the management of SOD has not been investigated.

Surgical Therapy Surgery was the traditional therapy of SOD. The surgical approach, most commonly, is a transduodenal biliary sphincteroplasty with a transampullary septoplasty (pancreatic septoplasty). Sixty to seventy percent of patients were reported to have benefited from this therapy during a 1-10 year follow-up [61, 62]. Patients with an elevated basal sphincter pressure determined by intraoperative SOM were more likely to improve from surgical sphincter ablation than those with a normal basal pressure [62]. Some reports have suggested that patients with biliary-type pain have a better outcome than patients with idiopathic pancreatitis while others suggested no difference [61, 62]. However, most studies found that symptom improvement following surgical sphincter ablation alone was relatively uncommon in patients with established chronic pancreatitis [62]. The surgical approach for SOD has largely been replaced by endoscopic therapy. Patient tolerance, cost of care, morbidity, mortality, and cosmetic results are some of the factors that favor an initial endoscopic approach. At present, surgical therapy is reserved for patients with restenosis following endoscopic sphincterotomy and when endoscopic evaluation and/or therapy is not available or technically feasible. In many centers, however, operative therapy continues to be the standard treatment of pancreatic sphincter hypertension [7, 63].
Endoscopy Therapy Endoscopic sphincterotomy. Endoscopic sphincterotomy is the current standard therapy for patients with SOD. Most data on endoscopic sphincterotomy relates to biliary sphincter ablation alone. Clinical improvement following therapy has been reported to occur in 55-95% of patients (Table 1). These variable outcomes are reflective of the different criteria used to document SOD, the degree of obstruction (Type I biliary patients appear to have a better outcome than Type II and III), the methods of data collection (retrospective vs. prospective), and the techniques used to determine benefit. Rolny and colleagues [64] studied 17 Type I post-cholecystectomy biliary patients by SOM. In this series, 65% had an abnormal SOM (although not specifically stated, it appears that the biliary sphincter was studied alone). Nevertheless, during a mean follow-up interval of 2.3 years, all patients benefited from biliary sphincterotomy. The results of this study suggested that since Type I biliary patients invariably benefit from biliary sphincterotomy, SOM in this patient group is not only unnecessary, but it may also be misleading. The results of this study, however, have never been validated at another center. Although most of the studies reporting efficacy of endoscopic therapy in SOD have been retrospective, three notable randomized trials have now been reported. In a landmark study by Geenen and associates [65], 47 post-cholecystectomy Type II biliary patients were randomized to biliary sphincterotomy or sham sphincterotomy. SOM was performed in all patients but not used as a criterion for randomization. During a 4-year follow-up, 95% of patients with an elevated basal sphincter benefited from sphincterotomy. In contrast, only 30-40% of patients with an elevated sphincter pressure treated by sham sphincterotomy or with a normal sphincter pressure treated by endoscopic sphincterotomy or sham sphincterotomy benefited from this therapy. The two important findings of this study were that SOM predicted the outcome from endoscopic sphincterotomy and that endoscopic sphincterotomy offered long-term benefit in Type II biliary patients with SOD.

Table 3a. Change in the mean pain score (using a 0-none to 10-most severe linear pain scale) and number of hospital days per month required for pain in patients with manometrically documented sphincter of Oddi dysfunction randomized to endoscopic sphincterotomy (ES), sham sphincterotomy (S-ES), and surgical sphincteroplasty with or without cholecystectomy (SSp± CCx).

Therapy............. Follow-up............Mean pain score.................Hospital days/month.........% patients
................................(yrs).................Pre-Rx...Post-Rx..................Pre-Rx........Post-Rx............improved
ES (n=19)...............3.3.....................9.2.........3.9a........................0.85............0.23b.................68%c
S-ES (n=17)...........2.2.....................9.4.........7.2...........................0.87.............0.89...................24%
SSp±CCx (n=16)...3.4.....................9.4.........3.3a........................0.94............0.27b.................69%c


a P<0.04; b P=0.002; c P=0.009; ES and SSp±CCx vs. S-ES
Adapted from reference [66]


Table 3b. Clinical benefit correlated with sphincter of Oddi dysfunction (SOD) type.

SOD Type*.....Patients improved / total patients
.........................ES...................S-ES............SSp±CCx
Type II............5/6 (83%)a....1/7 (14%).......8/10 (80%)a
Type III...........8/13 (62%)....3/10 (30%).....3/6 (50%)

* SOD type based on Hogan-Geenen SOD classification system
a P<0.02; ES and SSp±CCx vs. S-ES
Adapted from reference [66]


Sherman and associates [66] reported their preliminary results of a randomized study comparing endoscopic sphincterotomy, surgical biliary sphincteroplasty with pancreatic septoplasty (with or without cholecystectomy) to sham sphincterotomy for Type II and III biliary patients with manometrically documented SOD. The results are shown on Tables 3a and 3b. During a 3.0 year follow-up period, 69% of patients undergoing endoscopic or surgical sphincter ablation improved compared to 24% in the sham sphincterotomy group (P=0.009). There was a trend for Type II patients to benefit more frequently from sphincter ablation than Type III (13/16, 81% vs. 11/19, 58%; P=0.14). Evidence is now accumulating that the addition of a pancreatic sphincterotomy to an endoscopic biliary sphincterotomy in such patients may improve the outcome (see below). Long-term outcome studies, preferably in randomized trials, are awaited.

In a third study [67, 68], post-cholecystectomy patients with biliary-type pain (mostly Type II) were prospectively randomized to endoscopic sphincterotomy or sham following stratification according to SOM. Eighty-five percent (11 of 13) of patients with elevated basal pressure improved at 2 years after endoscopic sphincterotomy, while 38% (5 of 13) of patients improved after a sham procedure (P=0.041). Patients with normal SOM were also randomized to sphincterotomy or sham. The outcome was similar for the two groups (8 of 13 improved after sphincterotomy and 8 of 19 improved after sham; P=0.47).

These results clearly indicate that the response rate and enthusiasm for sphincter ablation must be correlated with patient presentation and balanced against the high complication rates reported for endoscopic therapy of SOD. Most studies indicate that patients undergoing endoscopic sphincterotomy for SOD have complication rates 2-5 times higher than patients undergoing endoscopic sphincterotomy for ductal stones [69, 70]. Pancreatitis is the most common complication occurring in up to 20% of patients. Endoscopic techniques are being developed (e.g., pancreatic duct stenting prior to combined pancreaticobiliary sphincterotomy and pancreatic stenting after biliary sphincterotomy) to limit such complications [71].

Balloon dilation and stenting. Balloon dilation of strictures in the gastrointestinal tract has become commonplace. In an attempt to be less invasive and possibly preserve sphincter function, adaptation of this technique to treat SOD has been described. Unfortunately because of the unacceptably high complication rates, primarily pancreatitis, this technology has little role in the management of SOD [72]. Similarly, although biliary stenting might offer short-term symptom benefit in patients with SOD and predict outcome from sphincter ablation, it too has unacceptably high complication rates and cannot be advocated in this setting based on the available data [54].

Botulinum toxin injection. Botulinum toxin (Botox), a potent inhibitor of acetylcholine release from nerve endings, has been successfully applied to smooth muscle disorders of the gastrointestinal tract such as achalasia. In a preliminary clinical trial, Botox injection into the SO resulted in a 50% reduction in the basal sphincter pressure and improved bile flow [73]. This reduction in pressure may be accompanied by symptom improvement in some patients. Although further study is warranted, Botox may serve as a therapeutic trial for SOD with responders undergoing permanent sphincter ablation. One such study has recently been reported [74]. Twenty-two post-cholecystectomy Type III patients with manometric evidence of SOD underwent Botox injection into the intraduodenal sphincter segment. Overall, 11 of the 12 patients who responded to botulinum toxin versus 2 of 10 patients who did not gain pain relief, later benefited from endoscopic sphincterotomy (P<0.01).

SOD in Recurrent Pancreatitis

Disorders of the pancreatic sphincter can give rise to pancreatitis or episodic pain suggesting a pancreatic origin [63]. SOD has been manometrically documented in 15 to 72% of patients with recurrent pancreatitis, previously labeled as idiopathic [17, 18, 19, 75]. Biliary sphincterotomy alone has been reported to prevent further pancreatitis episodes in more than 50% of such patients. From a scientific, but not practical viewpoint, care must be taken to separate out subtle biliary pancreatitis [76] which will similarly respond to biliary sphincterotomy.

The value of ERCP, SOM and sphincter ablation therapy was studied in 51 patients with idiopathic pancreatitis [39]. Twenty-four (47.1%) had an elevated basal sphincter pressure. Thirty were treated by biliary sphincterotomy (n=20), or surgical sphincteroplasty with pancreatic septoplasty (n=10). Fifteen of 18 patients (83%) with an elevated basal sphincter pressure had long-term benefit (mean follow-up, 38 months) from sphincter ablation therapy (including 10 of 11 treated by biliary sphincterotomy) in contrast to only 4 of 12 (33.3%, P<0.05) with a normal basal sphincter pressure (including 4 of 9 treated by biliary sphincterotomy). However, Guelrud et al. [77] found that severance of the pancreatic sphincter was necessary to resolve the pancreatitis (Table 4). In this series, 69 patients with idiopathic pancreatitis due to SOD underwent treatment by standard biliary sphincterotomy (n=18), biliary sphincterotomy with pancreatic sphincter balloon dilation (n=24), biliary sphincterotomy followed by pancreatic sphincterotomy in separate sessions (n=13), or combined pancreatic and biliary sphincterotomy in the same session (n=14). Eighty-one percent of patients undergoing pancreatic and biliary sphincterotomy had resolution of their pancreatitis compared to 28% of patients undergoing biliary sphincterotomy alone (P<0.005). These data are consistent with the theory that many such patients who benefit from biliary sphincterotomy alone have subtle gallstone pancreatitis. The results of Guelrud et al. [77] also support the anatomic findings of separate biliary and pancreatic sphincters, and the manometry findings of residual pancreatic sphincter hypertension in more than 50% of persistently symptomatic patients who undergo biliary sphincterotomy alone. Toouli et al. [78] also demonstrated the importance of pancreatic and biliary sphincter ablation in patients with idiopathic pancreatitis. In this series, 23 of 26 patients (88%) undergoing surgical ablation of both the biliary and pancreatic sphincter were either asymptomatic or had minimal symptoms at a median follow-up of 24 months (range, 9-105 months). Okolo and colleagues [79] retrospectively evaluated the long-term results of endoscopic pancreatic sphincterotomy in 55 patients with presumed (recurrent pancreatitis with pancreatic duct dilation and contrast medium drainage time from the pancreatic duct greater than 10 minutes) or manometrically documented pancreatic sphincter dysfunction. During a median follow-up of 16 months (range, 3-52 months), 34 patients (62%) reported significant pain improvement. Patients with normal pancreatograms were more likely to respond to therapy than were those with pancreatographic evidence of chronic pancreatitis (73% vs. 58%).

Table 4. Pancreatic sphincter dysfunction and recurrent pancreatitis: response to sphincter therapy.

Treatment................................................................Patients improved
................................................................................../ total patients

Biliary sphincterotomy alone.................................5/18 (28%)

Biliary sphincterotomy followed by.......................13/24 (54%)
pancreatic sphincter balloon dilation

Biliary sphincterotomy plus pancreatic.................10/13 (77%)a
sphincterotomy at later session


Biliary sphincterotomy and pancreatic..................12/14 (86%)a
sphincterotomy at same session

a P<0.005 vs. biliary sphincterotomy alone
Adapted from reference [77]


Currently, the best method to treat residual pancreatic sphincter stenosis after biliary sphincterotomy awaits further study. Patients with idiopathic pancreatitis who fail to respond to biliary sphincterotomy alone should have their pancreatic sphincter reevaluated and be considered for sphincter ablation if residual high pressure is found.

Failure to Achieve Symptomatic Improvement after Biliary Sphincterectomy

Table 5 lists several potential explanations as to why patients may fail to achieve symptom relief after biliary sphincterotomy is performed for well-documented sphincter of Oddi dysfunction. First, the biliary sphincterotomy may have been inadequate or restenosis may have occurred. Although the biliary sphincter is commonly not totally ablated [80], Manoukian et al. indicate that clinically significant biliary restenosis occurs relatively infrequently [81]. If no "cutting space" remains in such a patient, balloon dilation to 8-10 mm may suffice, but long-term outcome from such therapy is unknown [72].

Table 5. Causes for failure to achieve symptom relief after biliary sphincterotomy in sphincter of Oddi dysfunction.

1. Residual or recurrent biliary sphincter dysfunction
2. Pancreatic sphincter (major papilla) dysfunction
3. Chronic pancreatitis - subtle, pancreatogram normal
4. Other obstructive pancreatobiliary pathology (stones, strictures, tumor, pancreas divisum)
5. Non-pancreatobiliary disease - especially gut motor disorders or irritable bowel syndrome


Second, the importance of pancreatic sphincter ablation is being increasingly recognized, as noted in the data preliminarily reported by Guelrud et al. [77]. Eversman and colleagues found that 90% of patients with persistent pain or pancreatitis after biliary sphincterotomy had residual abnormal pancreatic basal pressue [82]. Soffer and Johlin reported that 25 of 26 patients (mostly Type II), who failed to respond to biliary sphincterotomy, had elevated pancreatic sphincter pressure [83]. Endoscopic pancreatic sphincterotomy was performed with overall symptomatic improvement in two thirds of patients. Elton and colleagues [84] performed pancreatic sphincterotomy on 43 Type I and Type II SOD patients who failed to benefit from biliary sphincterotomy alone. During the follow-up period, 72% were symptom-free and 19% were partially or transiently improved.

Third, patients may fail to respond to sphincterotomy because they have chronic pancreatitis. These people may or may not have abnormal pancreatograms. Intraductal pancreatic juice aspiration after secretin stimulation may help make this diagnosis [85, 86]. Endoscopic ultrasound may show parenchymal and ductular changes of the pancreas in some of these patients suggesting chronic pancreatitis [87].

Fourth, some patients may be having pain from altered gut motility of the stomach, small bowel or colon (irritable bowel or pseudo-obstruction variants). There is increasing evidence that upper GI motility disorders may masquerade as pancreatobiliary-type pain (i.e., discrete right upper quadrant pain). Multiple preliminary studies show disordered duodenal motility in such patients [88, 89, 90]. This area needs much more study to determine the frequency, significance, and/or coexistence of these motor disorders along with SOD. A recent study [91] suggested that Type III patients have duodenal specific visceral hyperalgesia with pain reproduction by duodenal distention. These patients were also shown to have high levels of somatization, depression, obsessive-compulsive behavior, and anxiety compared to control subject [92].

Summary

In summary, our knowledge of sphincter of Oddi dysfunction and manometric techniques to assist in this diagnosis are evolving. Successful endoscopic SOM requires good general ERCP skills and careful attention to the main details listed above. If SOD is suspected in a Type III or mild to moderate pain level Type II patient, medical therapy should generally be tried. If medical therapy fails or is bypassed, ERCP and manometric evaluation are recommended. The role of less-invasive studies remains uncertain due to undefined sensitivity and specificity. Sphincter ablation is generally warranted in symptomatic Type I patients and Type II and III patients with abnormal manometry. The symptom relief rate varies from 55 to 95%, depending on the patient presentation and selection. Initial non-responders require thorough pancreatic sphincter and pancreatic parenchymal evaluation. SOD patients have relatively high complication rates after invasive studies or therapy. Thorough review of the risk: benefit ratio with individual patients is mandatory.

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Kozarek RA. Pancreatic stents can induce ductal changes consistent with chronic pancreatitis. Gastrointest Endosc 1990; 36:93-5. [More details]

Goff JS. Common bile duct sphincter of Oddi stenting in patients with suspected sphincter of Oddi dysfunction. Am J Gastroenterol 1995; 90:586-9. [More details]

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Guelrud M, Mendoza S, Rossiter G, Ramirez L, Barkin J. Effect of nifedipine on sphincter of Oddi motor activity: studies in healthy volunteers and patients with biliary dyskinesia. Gastroenterology 1988; 95:1050-5. [More details]

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; 33:477-85. [More details]

Sand J, Nordback I, Koskinen M, Matikainen M, Lindholm TS. Nifedipine for suspected Type II sphincter of Oddi dyskinesia. Am J Gastroenterol 1993; 88:530-5. [More details]

Guelrud M, Rossiter A, Souney P, Mendoza S, Mujica V. The effect of transcutaneous nerve stimulation on sphincter of Oddi pressure in patients with biliary dyskinesia. Am J Gastroenterol 1991; 86:581-5. [More details]

Lee SK, Kim MH, Kim HJ, Seo DS, Yoo KS, Joo YH, et al. Electroacupuncture may relax the sphincter of Oddi in humans. Gastrointest Endosc 2001; 53:211-6. [More details]

Moody FG, Vecchio R, Calabuig R, Runkel N. Transduodenal sphincteroplasty with transampullary septectomy for stenosing papillitis. Am J Surgery 1991; 161:213-8. [More details]

Sherman S, Hawes RH, Madura J, Lehman GA. Comparison of intraoperative and endoscopic manometry of the sphincter of Oddi. Surg Gynecol Obstet 1992; 175:410-18. [More details]

Chen JW, Saccone GT, Toouli J. Sphincter of Oddi dysfunction and acute pancreatitis. Gut 1998; 43:305-8. [More details]

Rolny P, Geenen JE, Hogan WJ. Post-cholecystectomy patients with ‘objective signs’ of partial bile outflow obstruction: clinical characteristics, sphincter of Oddi manometry findings, and results of therapy. Gastrointest Endosc 1993; 39:778-81. [More details]

Geenen JE, Hogan WJ, Dodds WJ, Toouli J, Venu RP. The efficacy of endoscopic sphincterotomy after cholecystectomy in patients with sphincter of Oddi dysfunction. N Engl J Med 1989; 320:82-7. [More details]

Sherman S, Lehman GA, Jamidar P, Hawes RH, Silverman W, Madura J, et al. Efficacy of endoscopic sphincterotomy and surgical sphincteroplasty for patients with sphincter of Oddi dysfunction (SOD): randomized, controlled study. Gastrointest Endosc 1994; 40:A125. [More details]

Toouli J, Roberts-Thomson I, Kellow J, et al. Prospective randomized trial of endoscopic sphincterotomy for treatment of sphincter of Oddi dysfunction. J Gastroenterol Hepatol 1996; 11:A115. [More details]

Toouli J, Roberts-Thomson IC, Kellow J, Dowsett J, Saccone GT, Evans P, et al. Manometry based randomized trial of endoscopic sphincterotomy for sphincter of Oddi dysfunction. Gut 2000; 46:98-102. [More details]

Sherman S, Ruffolo TA, Hawes RH, Lehman GA. Complications of endoscopic sphincterotomy. A prospective series with emphasis on the increased risk associated with sphincter of Oddi dysfunction and nondilated bile ducts. Gastroenterology 1991; 101:1068-75. [More details]

Freeman ML, Nelson DB, Sherman S, Haber GB, Herman ME, Dorsher PJ, et al. Complications of endoscopic biliary sphincterotomy. N Engl J Med 1996; 35:909-8. [More details]

Tarnasky PR, Palesch YY, Cunningham JT, Mauldin PD, Cotton PB, Hawes RH. Pancreatic stenting prevents pancreatitis after biliary sphincterotomy in patients with sphincter of Oddi dysfunction. Gastroenterology 1998; 115:1518-24. [More details]

Kozarek RA. Balloon dilation of the sphincter of Oddi. Endoscopy 1988; 20(Suppl 1):207-10. [More details]

Pasricha PJ, Miskovsky EP, Kalloo AN. Intrasphincteric injection of botulinum toxin for suspected sphincter of Oddi dysfunction. Gut 1994; 35:1319-21. [More details]

Wehrmann T, Seifert H, Seipp M, Lembeke B, Caspary WF. Endoscopic injection of botulinum toxin for biliary sphincter of Oddi dysfunction. Endoscopy 1998; 30:702-7. [More details]

Kuo WH, Pasricha PJ, Kalloo AN. The role of sphincter of Oddi manometry in the diagnosis and therapy of pancreatic disease. Gastrointest Endosc Clin N Am 1998; 8:79-85. [More details]

Ros E, Navarro S, Bru C, Garcia-Puges A, Valderrama R. Occult microlithiasis in ‘idiopathic’ acute pancreatitis: prevention of relapses by cholecystectomy or ursodeoxycholic acid therapy. Gastroenterology 1991; 101:1701-9. [More details]

Guelrud M, Plaz J, Mendoza S, Beker B, Rojas O, Rossiter G. Endoscopic treatment in Type II pancreatic sphincter dysfunction. Gastrointest Endosc 1995; 41:A398. [More details]

Toouli J, Di Francesco V, Saccone G, Kollias J, Schloithe A, Shanks N. Division of the sphincter of Oddi for treatment of dysfunction associated with recurrent pancreatitis. Br J Surg 1996; 83:1205-10. [More details]

Okolo PI 3rd, Pasricha PJ, Kalloo AN. What are the long-term results of endoscopic pancreatic sphincterotomy?. Gastrointest Endosc 2000; 52:15-9. [More details]

Heinerman PM, Graf AH, Boeckl O. Does endoscopic sphincterotomy destroy the function of Oddi’s sphincter?. Arch Surg 1994; 129:876-80. [More details]

Manoukian AV, Schmalz MJ, Geenen JE, Hogan WJ, Venu RP, Johnson GK. The incidence of post-sphincterotomy stenosis in group II patients with sphincter of Oddi dysfunction. Gastrointest Endosc 1993; 39:496-8. [More details]

Eversman D, Fogel E, Phillips S, Sherman S, Lehman G. Sphincter of Oddi dysfunction (SOD): long-term outcome of biliary sphincterotomy (BES) correlated with abnormal biliary and pancreatic sphincters. Gastrointest Endosc 1999; 49(Suppl. 3):78AB. [More details]

Soffer EE, Johlin FC. Intestinal dysmotility in patients with sphincter of Oddi dysfunction. A reason for failed response to sphincterotomy. Dig Dis Sci 1994; 39:1942-6. [More details]

Elton E, Howell DA, Parsons WG, Qaseem T, Hanson BL. Endoscopic pancreatic sphincterotomy: indications, outcome, and a safe stentless technique. Gastrointest Endosc 1998; 47:240-9. [More details]

Gregg JA. The intraductal secretin test (IDST): an adjunct to the diagnosis of pancreatic disease and pancreatic physiology. In: Sivak MV, ed. Gastroenterologic Endoscopy. Philadelphia: WB Saunders Co, 1987. [More details]

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Wiersema MJ, Hawes RH, Lehman GA, Kochman ML, Sherman S, Kopecky KK. Prospective evaluation of endoscopic ultrasonography and endoscopic retrograde cholangiopancreatography in patients with chronic abdominal pain of suspected pancreatic origin. Endoscopy 1993; 25:555-64. [More details]

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Chun A, Desautels S, Slivka A, Mitrani C, Starz T, Di Lorenzo C, Wald A. Visceral algesia in irritable bowel syndrome, fibromyalgia, and sphincter of Oddi dysfunction, Type III. Dig Dis Sci 1999; 44:631-6. [More details]

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Key words Cholangiopancreatography, Endoscopic Retrograde; Manometry; Oddi's Sphincter; Pancreatitis, Acute Necrotizing; Sphincterotomy, Endoscopic


Abbreviations CAT: computerized axial tomography; MMC: migrating motor complex; SO: sphincter of Oddi; SOD: sphincter of Oddi dysfunction; SOM: SO manometry; TENS: transcutaneous electrical nerve stimulation; VIP: vasoactive intestinal peptide


Acknowledgment The authors are grateful to Tina Jackson for the technical preparation of this document


Correspondence
Stuart Sherman
Division of Gastroenterology/Hepatology
Indiana University Medical Center
550 North University Boulevard, Suite 2300
Indianapolis
IN 46202-5000
USA
Phone: +1-317-274-0925
Fax: +1-317-278-0164
E-mail address: ssherman@iupui.edu

Thursday, May 17, 2007

UCLA Center for Advanced Endoscopy & the Pancreaticobiliary Center

Go to UCLA

There are two main types of sphincter of Oddi dysfunction. A clinical syndrome with predominance of biliary-type pain, abnormalities of liver enzymes, and dilation of the bile duct will be referred to as biliary-type sphincter of Oddi dysfunction. Another variant with predominance of pancreatic problems, mainly recurrent episodes of acute pancreatitis is known as pancreatic-type sphincter of Oddi dysfunction.

Biliary-type pain is typically located in the right upper quadrant area of the abdomen, the area in the upper abdomen below the right side of the rib cage. It can sometimes radiate to the shoulder blade or to the mid-back. It commonly occurs after the ingestion of meals, in particular after nutrients with a high fat content. The pain is constant and typically persists for 45 minutes up to several hours. Most patients who present with these symptoms are initially thought to have gallbladder problems, and frequently undergo cholecystectomy. However, their symptoms persist following cholecystectomy. This is the reason why biliary-type sphincter of Oddi dysfunction is sometimes also referred to as post-cholecystectomy syndrome. Strictly speaking, however, post-cholecystectomy syndrome is a rather broad term used to describe abdominal pain symptoms of varying etiologies that can persist or occur after a cholecystectomy. The causes of post-cholecystectomy syndrome may include conditions such as sphincter of Oddi dysfunction or even irritable bowel syndrome (IBS)..."
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Monday, April 16, 2007

Sphincter of Oddi Wikipedia



Sphincter of Oddi
From Wikipedia, the free encyclopedia

The Sphincter of Oddi, also called the hepatopancreatic sphincter or Glisson's sphincter, controls secretions from the liver, pancreas, and gallbladder into the duodenum of the small intestine.


It is a sphincter muscle located at the surface of the duodenum. It appears slightly distal to the joining of the common bile duct and pancreatic duct as they enter the descending duodenum and forms from the ampulla of Vater. Bile and pancreatic secretions enter the digestive system through this point. The opening on the inside of the descending duodenum after the sphincter of Oddi is called the amajor duodenal papilla.


Clinical significance
Endoscopic retrograde cholangiopancreatograms (ERCPs), which are radiographic examinations of the biliary system, often involve assessment of the bile ducts with a duodenoscope via the sphincter of Oddi before the injection of iodinated contrast medium.


External links
synd/2709 at Who Named It
Diagram at sunderland.ac.UK
Retrieved from "http://en.wikipedia.org/wiki/Sphincter_of_Oddi"
Categories: Digestive system Gastroenterology



To view information on other digestive disease, click on Digestive Diseases Library.
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Article by Walter J. Hogan, MD

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Sphincter of Oddi Dysfunction
At the request of one of my readers, I've posted some more information about the Sphincter of Oddi and its dysfunction.

It’s a long read, the first part is a writeup on some background info, and the second is about treatment options. Enjoy!



Clinical manifestations and diagnosis of sphincter of Oddi dysfunction

Walter J Hogan, MD

UpToDate performs a continuous review of over 350 journals and other resources. Updates are added as important new information is published. The literature review for version 14.2 is current through April 2006; this topic was last changed on May 15, 2006. The next version of UpToDate (14.3) will be released in October 2006.

INTRODUCTION — The sphincter of Oddi 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 (show 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 clinical manifestations and diagnosis of sphincter of Oddi dysfunction will be reviewed here. The treatment of this disorder is discussed separately. (See “Treatment of sphincter of Oddi dysfunction”).

ANATOMY — The sphincter of Oddi (SO) is composed of small circular and longitudinal muscular segments that are approximately 6 to 10 mm in total length and are contained mostly within the wall of the duodenum (show figure 1) [1]. The muscle fibers surround the intraduodenal segment of the common bile duct and the ampulla of Vater. A circular aggregate of muscle fibers known as the sphincter choledochus (or sphincter of Boyden) maintains resistance to bile flow, and thereby permits filling of the gallbladder during fasting and prevents retrograde reflux of duodenal contents into the biliary tree. A separate structure, called the sphincter pancreaticus, encircles the distal pancreatic duct. The muscle fibers of the sphincter pancreaticus are interlocked with those of the sphincter choledochus in a figure eight pattern. Although the pancreatic and biliary sphincter portions of the SO can be distinguished anatomically, their manometric features are similar and a direct anatomic and manometric correlation has not been established.

The muscle fibers of the SO function independently from those of the duodenal musculature. The motility of the SO is complex and not completely understood, but is known to vary in the fasting and fed states.

During fasting, SO motility is integrated with the migrating motor complex (MMC), permitting coordinated release of bile into the duodenum. Myoelectrical potentials within the SO increase during phase one of the MMC, reach a maximum during phase three, and then decrease rapidly.
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During the fed state, myoelectrical potentials within the SO vary depending upon the type and quantity of nutrients ingested and may be influenced by endogenous hormones such as cholecystokinin [2,3].
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DEFINITIONS — A great deal has been written about the sphincter of Oddi and its dysfunction, but the literature is often difficult to interpret because of differences in nomenclature [4]. The terms papillary stenosis, sclerosing papillitis, biliary spasm, biliary dyskinesia, and postcholecystectomy syndrome have been used synonymously with sphincter of Oddi dysfunction (SOD). Despite this source of confusion, two separate pathologic entities are widely recognized based upon their distinct pathogenic mechanisms [5,6].


  • Sphincter of Oddi stenosis
  • Sphincter of Oddi dyskinesia

Sphincter of Oddi stenosis is an anatomic abnormality associated with narrowing of the SO. It can result from any process leading to inflammation or scarring such as pancreatitis, passage of a gallstone through the papilla, intraoperative trauma, infection, and adenomyosis. Sphincter of Oddi stenosis is associated with abnormal SO motility and elevated basal pressure.

Sphincter of Oddi dyskinesia refers to a functional disturbance of the SO, leading to intermittent biliary obstruction. The cause of SO dyskinesia is not well understood. Spasm and relaxation of the SO can be induced pharmacologically with agents known to affect smooth muscle function (such as nitroglycerin), suggesting that the spasm may be influenced by local hormonal or neurologic disturbance.

CLINICAL MANIFESTATIONS — Sphincter of Oddi dysfunction has been associated with two clinical syndromes: biliary pain and pancreatitis. The prevalence of SOD among patients with these conditions is difficult to estimate because of several potential sources of bias among studies evaluating SOD in these settings:


  • The amount of investigation for other causes of symptoms differed.
  • The diagnostic “gold-standard” for SOD varied.
  • The diagnosis of SOD usually involves invasive testing. As a result, most studies have not included an adequate control group.

Biliary pain — Sphincter of Oddi dysfunction is suspected in patients who have biliary-type pain without other apparent causes. In this setting:


  • SOD is most commonly recognized in patients who have undergone Cholecystectomy (hence the name postcholecystectomy syndrome).
  • The reasons for this are not well understood, but may be related to unmasking of preexisting SOD due to removal of the gallbladder, which may have served as a reservoir to accommodate increased pressure in the biliary system occurring during sphincter spasm [7].
  • Another possible explanation is alteration of SO motility due to the severing of nerve fibers that pass between the gallbladder and SO via the cystic duct [8].
  • However, SOD also occurs in patients whose gallbladders are intact, suggesting that other pathophysiologic mechanisms are involved [9].

Despite the association of SOD with cholecystectomy, SOD is an uncommon occurrence following cholecystectomy [10]. In one series of 454 patients who had undergone cholecystectomy, the prevalence of SOD dysfunction was estimated to be less than 1 percent [11].

Pancreatitis — The cause of pancreatitis escapes routine diagnostic studies in some patients. (See “Clinical manifestations and diagnosis of acute pancreatitis”, section on Diagnosis of the etiology of acute pancreatitis). SO dysfunction has been hypothesized as a cause of idiopathic recurrent pancreatitis and pancreatitis occurring after endoscopic retrograde cholangiopancreatography (ERCP) [12,13]. (See “Post-ERCP pancreatitis”).

Abnormalities of the pancreatic or biliary sphincter in association with recurrent idiopathic pancreatitis have been demonstrated in several studies [14-16]. However, whether SOD gives rise to, or is a result of pancreatitis has not been proven. In one study, for example, among 32 patients with a known cause for chronic pancreatitis (alcohol, annular pancreas, and biliary causes), seven (22 percent) had elevated basal SO pressures compatible with SOD [14].

Another study evaluated 104 patients who had SO manometry to investigate unexplained upper abdominal pain; all had previously undergone investigation for chronic pancreatitis by pancreatic ductography, endoscopic ultrasound, and pancreatic fluid bicarbonate determination [16]. Of the 68 patients found to have SOD, 29 percent had structural evidence of chronic pancreatitis, while SOD dysfunction was present in 20 of 23 (87 percent) patients found to have chronic pancreatitis.

Evidence that SOD can cause pancreatitis was suggested in an animal model in which transient sphincter contraction induced by application of topical carbachol abolished trans-sphincteric flow and increased pancreatic exocrine secretion and pancreatic duct pressure to levels comparable with that seen in pancreatic duct ligation [17]. The addition of cholecystokinin/secretin stimulation of pancreatic secretion plus carbachol application caused pancreatic tissue damage and an increase in serum amylase levels.

Natural history — Few studies have addressed the long-term natural history of SOD. The available data suggest that the clinical course is variable depending in part upon the initial biliary classification (see “Classification systems” belowsee “Classification systems” below). In a one-year follow-up study, seven type II patients with abnormal 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. 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 [18].

DIAGNOSIS — The diagnosis of SOD is established by SO manometry, which is performed during ERCP. Several less invasive methods have also been evaluated for establishing the diagnosis, but none has proven to be consistently more accurate in controlled clinical trials [19,20]. This section will first review clinical criteria in which the diagnosis should be considered and then discuss the tests for biliary and pancreatic SOD and SO manometry, which remains the gold standard for the diagnosis.

Rome III criteria — Clinical criteria for diagnosis of functional gallbladder and sphincter of Oddi disorders have been proposed based mainly upon expert consensus [21]. These criteria (known as the Rome III criteria) specify three subsets of functional gallbladder and sphincter of Oddi disorders and also recognize a pancreatic sphincter of Oddi disorder.

The three gallbladder and biliary sphincter disorders are:


  • Functional gallbladder disorder
  • Functional biliary sphincter of Oddi disorder
  • Functional pancreatic sphincter of Oddi disorder


The guidelines stress that patients with upper abdominal pain who do not meet the Rome III symptom-based criteria should not be submitted to ERCP or other invasive procedures. Those who fulfill the criteria should be assessed initially with noninvasive procedures and eventually with therapeutic trials that will more likely identify the majority of patients whose pain is not biliopancreatic in origin and will therefore not require further investigation.

Functional gallbladder and sphincter of Oddi disorders — The following are the Rome III criteria for functional gallbladder and sphincter of Oddi disorders (functional gallbladder, biliary and pancreatic sphincter of Oddi disorders described above are subsets of this grouping)

Must include episodes of pain located in the epigastrium and/or right upper quadrant and ALL the following:

  • Episodes lasting 30 minutes or longer
  • Recurrent symptoms occurring at different intervals (not daily)
  • The pain builds up to a steady level
  • The pain is moderate to severe enough to interrupt the patients’ daily activities or lead to an emergency department visit
  • The pain is not relieved by bowel movements
  • The pain is not relieved by postural change
  • The pain is not relieved by antacids
  • Exclusion of other structural disease that would explain the symptoms

Supportive criteria include: The pain may be present with one or more of the following:

  • pain associated with nausea and vomiting; pain radiates to the back and/or right infrasubscapular region;
  • pain awakens from sleep in the middle of the night
Functional gallbladder disorder — The following are the Rome III criteria for functional gallbladder disorder:


  • Criteria for functional gallbladder and sphincter of Oddi disorders fulfilled
  • Gallbladder is present
  • Normal liver enzymes, conjugated bilirubin, and amylase/lipase

Functional biliary sphincter of Oddi disorder — The following are the Rome III criteria for functional biliary sphincter of Oddi disorder.

Must include both of the following:


  • Criteria for functional gallbladder and sphincter of Oddi disorder
  • Normal amylase/lipase

Supportive criteria include:

  • elevated serum aminotransferases, alkaline phosphatase or conjugated bilirubin temporally related to at least two pain episodes.

Functional pancreatic sphincter of Oddi disorder — The following are the Rome III criteria for functional pancreatic sphincter of Oddi disorder.

Must include both of the following:


  • Criteria for functional gallbladder and sphincter of Oddi disorder
  • Elevated amylase/lipase

Biliary SOD — The presence of biliary SOD has been based upon a variety of parameters, including:

  • dilation of the common bile duct,
  • provocation tests,
  • hepatobiliary scintigraphy, and
  • a classification system.

Dilation of the common bile duct — Otherwise unexplained dilation of the common bile duct on ultrasound is associated with SOD and may predict a favorable response to sphincterotomy in patients with other clinical evidence of biliary obstruction (eg, pain, abnormal liver function tests) [22]. However, common bile duct dilation (more than 6 mm) may be observed in up to one-third of patients after cholecystectomy [23-25]. Furthermore, the size of the common bile duct increases with age [26]. As a result, dilation of the common bile duct alone is insufficient evidence for establishing the diagnosis of SOD. It should be considered in the context of symptoms, liver and pancreatic biochemical tests, and a history of multiple gallbladder stones or past removal of common bile duct stones. In most instances, mild dilation is an incidental finding warranting only observation.

Biliary provocation tests — To increase the specificity of common bile duct diameter measurement for determining SOD, several provocation tests have been developed that use either a fatty meal (fatty meal ultrasonography) or cholecystokinin to increase bile flow [27,28]. In patients who have normal SO function, the bile duct diameter remains constant or decreases following stimulation; an increase of more than 2 mm is considered to be pathologic [27].

Correlation of provocation tests with sphincter of Oddi manometry is poor and abnormal findings may be seen in non-biliary diseases. As an example, an abnormal response of the SO to CCK stimulation or the Nardi test has been observed in patients with irritable bowel syndrome [29,30].

Hepatobiliary scintigraphy — Hepatobiliary scintigraphy using technetium-99m labeled dyes can provide a standardized, semiquantitative assessment of delayed biliary drainage in patients whose gallbladder is absent [7,31-33]. In one study, 26 consecutive patients underwent hepatobiliary imaging, ERCP, and SO manometry [31]. A scintigraphic score (referred to as the Hopkin’s score) was constructed from quantitative and visual criteria that successfully discriminated all patients with SOD.

Substantially different conclusions were reached in another report in which scintigraphy results were compared with sphincter of Oddi manometry in 27 patients with suspected SOD following cholecystectomy [34]. Scintigraphy with cholecystokinin infusion was performed within one month of manometry. Scoring of the scans and measurement of the transit time from the hepatic hilum to the duodenum (HDTT) was performed by independent, blinded observers.

Eight patients had abnormal SO manometry (basal SO pressure >40 mmHg). Scintigraphy scoring had a sensitivity of 25 to 38 percent, a specificity of 86 to 89 percent, a positive predictive value of 40 to 60 percent, and a negative predictive value of 75 to 79 percent. The coefficient of variation between observers was 0.72 (ie, moderately good correlation). The sensitivity, specificity, positive and negative predictive values of the HDTT were 13, 95, 50, and 74 percent, respectively. The authors concluded that scintigraphy correlated poorly with manometry in postcholecystectomy patients with suspected SOD.

Clearance rates in patients with SOD overlap with those in a normal population [7]. In addition, scintigraphy may be falsely positive in patients who have extrahepatic biliary obstruction from a variety of causes, or falsely negative in patients who have SO dyskinesia in whom obstruction to bile flow may be intermittent. Furthermore, hepatobiliary scintigraphy cannot detect obstruction to flow arising from the pancreatic portion of the SO. Thus, scintigraphy should have only a supportive role in the evaluation of suspected SOD.

Classification systems — Several investigators have constructed criteria by which the likelihood of finding SOD and its response to treatment can be predicted. The best studied classification system for biliary SOD (known as the Milwaukee Biliary Group Classification) is based upon the number of laboratory, clinical, and radiologic features suggesting SOD in an individual patient. These have been revised in the Rome III statement as described below. The original Milwaukee classification recognizes three groups of patients who have biliary type pain without an identifiable cause prior to manometry [35]:

Type I patients fulfill all of three criteria:

  • (a) pain associated with abnormal serum aminotransferases (ALT and AST more than two times normal on at least two occasions);
  • (b) a dilated common bile duct more than 10 mm on ultrasound or 12 mm on ERCP; and
  • (c) delayed drainage of contrast from the common bile duct after more than 45 minutes in the supine position).

Type II patients have one or two of the above criteria.


Type III patients have none of the above criteria.


These criteria have been evaluated in a number of studies [7,36-39]. In one report, for example, 213 patients with pancreaticobiliary pain were evaluated by sphincter of Oddi manometry and ERCP [36]. Abnormal sphincter of Oddi manometry was found in 86, 55, and 28 percent of patients classified as Milwaukee groups I, II, and III, respectively.

However, the ability of these criteria to predict a favorable outcome in patients treated by sphincterotomy has varied among studies [37-41], and their role in management has been criticized [42]. In most series, patients in class I benefit from sphincterotomy; optimal therapy and the value of the Milwaukee criteria are less clear for patients who are class II and III. One study found no differences in outcomes among 73 Milwaukee type II and III patients with intractable biliary-type pain treated by sphincterotomy [38]. In contrast, in another series that included 108 patients with recurrent biliary-type pain after cholecystectomy, elevated SO pressure was found in 63 and 50 percent of Milwaukee type II and III patients, respectively [40]. Improvement in symptoms following sphincterotomy was noted in 70 and 39 percent of patients in the two groups.

Rome III revision — The Rome III consensus statement revised the classification to make it more applicable to clinical practice and, whenever possible, avoid invasive procedures such as ERCP. Thus, the revised system emphasizes noninvasive methods to evaluate common bile duct diameter and suggests that contrast drainage times are not practical currently.


  • Type I patients present with biliary-type pain; abnormal aminotransferases, bilirubin or alkaline phosphatase >2 times normal values documented on two or more occasions and a dilated bile duct greater than 8 mm diameter on ultrasound. Approximately 65 to 95 percent of these patients have manometric evidence of biliary SOD.
  • Type II patients present with biliary-type pain and one of the previously mentioned laboratory or imaging abnormalities. Approximately 50 to 63 percent of these patients have manometric evidence of biliary SOD.
  • Type III patients complain only of recurrent biliary-type pain and have none of the previously mentioned laboratory or imaging criteria. Approximately 12 to 59 percent of these patients have manometric evidence of biliary SOD.

Correlation of noninvasive tests with sphincter of Oddi manometry — As noted above, several studies have compared the accuracy of the noninvasive tests with SOD with manometry. One of the largest studies comparing the most commonly used methods involved 304 patients with suspected SOD who underwent manometry, fatty meal ultrasonography, and hepatobiliary scintigraphy [43]. The following observations were made:


  • 73 patients (24 percent) were diagnosed with SOD by manometry.
    Compared to sphincter of Oddi manometry as the gold-standard, the sensitivity and specificity of fatty meal ultrasonography was 21 and 97 percent, respectively.
    The sensitivity and specificity of hepatobiliary scintigraphy were 49 and 78 percent, respectively.
  • Hepatobiliary scintigraphy and fatty meal ultrasonography were both abnormal in 90, 50, and 40 percent of patients with Type I, II, and II SOD dysfunction, respectively.
  • A durable clinical response was observed in 40 of 73 patients (55 percent) who underwent sphincterotomy. Of those with SOD, 11 of 13 (85 percent) with abnormal hepatobiliary scintigraphy and fatty meal ultrasonography had a good long-term response.
  • These data suggest that the correlation of fatty meal ultrasonography and hepatobiliary scintigraphy with sphincter of Oddi manometry was poor. Combined use of hepatobiliary scintigraphy and fatty meal ultrasonography increased sensitivity compared to either alone. The accuracy of these tests decreased in relation to the probability of SOD as determined by the Milwaukee Biliary Group Classification. The authors suggest that despite the poor test characteristics, fatty meal ultrasonography and hepatobiliary scintigraphy may provide assistance in predicting the long-term response to sphincterotomy in patients with manometrically proven SOD.


Pancreatic SOD — Tests of SOD involving the pancreatic segment of the SO have focused on pancreatic outflow obstruction due to SO stenosis.

Pancreatic provocation tests — Provocation tests for evaluating pancreatic SOD are based upon a similar principle as provocation tests for biliary SOD. An increase in pancreatic duct diameter following secretin stimulation of more than 1.5 mm (assessed by transabdominal ultrasound or CT) lasting for more than 30 minutes is considered to be pathologic [44]. In one report evaluating this technique, a positive test was associated with good operative outcome in 90 percent of patients with suspected SO dysfunction [45]. However, these results have not been duplicated in other centers. In another study, the accuracy of the secretin ultrasound test was compared to manometry as the gold standard in 47 patients with acute pancreatitis; ultrasound findings in 35 healthy patients were used as controls [46]. The sensitivity and specificity of the secretin ultrasound was 88 and 82 percent, respectively.

  • The addition of endoscopic ultrasound (EUS) to the secretin stimulation test has been attempted to improve accuracy. In one report, for example, 20 patients underwent dynamic imaging of the pancreas using real-time endoscopic ultrasonography with secretin stimulation [47]. Of the seven patients who had SO dysfunction based upon manometric results, only four (57 percent) had an abnormal endoscopic ultrasound measurement. Only 1 of 13 patients with normal SO manometry had an abnormal endoscopic ultrasound study. The results suggested excellent negative and positive predictive values but poor overall sensitivity for this test (show table 1). (See “Glossary of common biostatistical and epidemiological terms”).
  • The secretin stimulation test has also been performed during magnetic resonance cholangiopancreatography (MRCP). A pilot study compared the results with manometry in 15 patients with idiopathic recurrent pancreatitis of whom six (40 percent) had documented sphincter dysfunction by manometry [48]. SOD was suggested by secretin MRCP in four patients (27 percent). Secretin MRCP and manometry were concordant in 13 of 15 patients (82 percent in those diagnosed with sphincter dysfunction by manometry, and 100 percent in those in whom sphincter dysfunction was excluded). Further studies are needed.

Classification systems — A classification system similar to the Milwaukee Biliary Group Classification has been developed for pancreatic SOD [36]. It recognizes three groups of patients who have recurrent pancreatitis and/or typical pancreatic pain of uncertain etiology:

Type I patients have all three of the following criteria:


  • (a) elevation of pancreatic enzymes (more than 1.5 times the upper limit of normal) associated with pain;
  • (b) a dilated pancreatic duct (greater than 6 mm in the head and more than 5 mm in the body by ERCP); and
  • (c) delayed drainage of contrast after ERCP (more than nine minutes).

Type II patients have or two of the above criteria.

Type III patients have none of the above criteria.

The accuracy of these criteria for predicting pancreatic SOD was evaluated in one study in which elevated basal sphincter pressure was found in 92, 58, and 35 percent in groups I, II, and III, respectively [36].

Sphincter of Oddi manometry — Sphincter of Oddi manometry remains the gold standard for diagnosis of SOD. The most common method involves retrograde intubation of the sphincter of Oddi with a pressure-transducing manometry catheter during ERCP. Basal pressure and phasic wave contractions are routinely recorded from the common bile duct and pancreatic duct segments of the sphincter of Oddi; the mechanical and electrical activity are similar between the two segments (show figure 2) [49]. Measurement of basal pressures from either the biliary or pancreatic duct alone may miss up to one-quarter of patients with abnormal sphincter pressure [50].

Patients with SO dysfunction have been divided into two groups based upon manometric findings:


  • Patients with structural alterations of the SO zone (stenosis)
  • Patients with functional abnormalities (dyskinesia)

Patients with stenosis are identified by an abnormally elevated basal SO pressure (>40 mmHg) (show figure 3). This finding is reproducible, and the elevated SO pressure does not relax following administration of smooth muscle relaxants.

Patients with SO dyskinesia may also have elevated basal SO pressure. However, in contrast to SO stenosis, the elevated pressure decreases dramatically following amyl nitrite inhalation or glucagon bolus injection, which relax smooth muscles. Other manometric characteristics of this group are: rapid SO contraction frequency (>7/min), an excess in retrograde phasic contractions (>50 percent), and a substantial basal SO pressure increase (paradoxical response) following administration of cholecystokinin-octapeptide (CCK-8) (show figure 4). Manometric findings in patients with SO dyskinesia are less well reproduced upon repeat measurement compared to patients with SO stenosis.

Limitations — Although SO manometry remains the gold standard for diagnosis of SOD, it is invasive, technically demanding, and has several limitations:

  • Most series have suggested that it is associated with an increased risk of pancreatitis. In an illustrative series of 100 consecutive patients who underwent sphincter of Oddi manometry, the overall incidence of pancreatitis (defined as upper abdominal pain associated with an elevation in serum amylase or lipase 24 hours after manometry) was 17 percent [51]. (This compares to an incidence of approximately 5 percent in patients undergoing ERCP for other indications.) The incidence was significantly increased in patients who had manometry plus ERCP during one session compared to those who had manometry alone (26 versus 9 percent). (See “Post-ERCP pancreatitis”).
  • No clinical or manometric criteria were able to predict the development of pancreatitis. Furthermore, on multivariate analysis, sphincterotomy was not associated with an increased risk of pancreatitis compared to ERCP alone. Placement of a pancreatic stent following biliary sphincterotomy may reduce the incidence of pancreatitis in patients with pancreatic sphincter hypertension [13]. In one report in which stenting was used, the level of the serum amylase obtained two hours after SO manometry predicted the development of pancreatitis [52]. (See “Treatment of sphincter of Oddi dysfunction”).

On the other hand, not all reports have reached this conclusion. A retrospective study of 268 patients who underwent elective ERCP categorized patients into two major groups:

  • those with suspected sphincter of Oddi dysfunction (cases) and
  • those with a bile duct stone (controls) [53].
The case group was further subclassified into two groups

  • (those who underwent sphincter of Oddi manometry followed by immediate ERCP, and
  • those who had an ERCP without manometry).
Similar to other reports, the rate of pancreatitis was much higher in the group with suspected sphincter of Oddi dysfunction (27 versus 3.2 percent). However, there was no significant difference in the rate of pancreatitis in those with sphincter of Oddi dysfunction who underwent manometry and ERCP compared with those who had and ERCP without manometry (OR 0.72, 95 percent CI 0.08 to 9.2). On multivariable analysis, biliary sphincterotomy and pancreatography were independent predictors of pancreatitis. Thus, the authors concluded that the higher risk of pancreatitis was not due to the manometry but rather to the underlying presence of sphincter of Oddi dysfunction.

The technique, equipment, and method of sedation used can affect the results. (See “Role of propofol and options for patients who are difficult to sedate for gastrointestinal endoscopy”).
The interpretation of results can vary among observers depending in part upon experience [54].
Prediction of response to treatment — Despite these limitations, the litmus test by which SO manometry can be judged is in its ability to predict a favorable response to treatment in patients with clinical manifestations of SOD.

Biliary-type pain — The most reliable finding predicting a favorable response to sphincterotomy in patients with biliary-type pain is elevated basal pressure. In one study, for example, 47 patients thought to have SOD based upon clinical findings were randomized to sphincterotomy or sham sphincterotomy prior to undergoing manometry [37]. At one-year follow-up, sphincterotomy improved pain scores and objective parameters in significantly more patients who had elevated basal sphincter pressures who underwent sphincterotomy (90 versus 25 percent). In contrast, pain scores were similar in patients without elevated pressure, regardless of treatment. Furthermore, the majority of patients with elevated basal pressures who underwent sham sphincterotomy benefited from subsequent sphincterotomy; these results persisted at four years’ follow-up.

Similar findings were noted in a study that included 81 patients who were randomly assigned to sphincterotomy or a sham procedure based upon the results of manometry [18]. The manometric record was categorized as SO stenosis, SO dyskinesia, or normal. In the SO stenosis group (comprised of 26 patients), symptoms improved significantly more often in those randomized to sphincterotomy (85 versus 39 percent). In contrast, results were not different in the sphincterotomy or sham groups in patients categorized as dyskinesia or normal. Interestingly, symptomatic outcome was not predicted by bile duct dilation, alteration of liver enzymes, or results of the morphine/neostigmine provocation test, a dissociation also observed by other investigators. Complications included mild pancreatitis in seven patients (14 episodes), one patient developed a fluid collection in the right upper quadrant, presumably related to a minor perforation. The endoscopic incision was extended in 19 patients after three months because of manometric evidence of incomplete division of the sphincter. The above observations suggest that patients classified as type II or higher who have manometric features characteristic of SO stenosis have a significant chance of improving following sphincterotomy [55].

Pancreatitis — Manometric findings in patients with idiopathic recurrent pancreatitis suggest that impedance to flow of pancreatic secretions may cause pancreatitis (show figure 3). This relationship was illustrated in a study of 35 patients with recurrent pancreatitis and no identifiable cause who were evaluated with SO manometry [56]. Twenty-six patients underwent total division of the pancreatic sphincter via open sphincterotomy and septectomy based upon abnormal SO manometry. After a median follow-up of 24 months, 15 (62 percent) of these patients were classified as “cured,” the majority of whom had SO stenosis.
Another report demonstrating the relationship of SOD with pancreatitis focused on the observation that a hypertensive pancreatic portion of the SO increases the risk of pancreatitis in patients undergoing ERCP with sphincterotomy [12]. Eighty patients with manometrically proven pancreatic sphincter hypertension were randomly assigned to stenting of the pancreatic SO segment after biliary sphincterotomy or sphincterotomy alone [12]. Patients who received a stent were significantly less likely to develop pancreatitis (7 versus 26 percent) [13]. The authors strongly suggested that stenting of the hypertensive pancreatic duct segment should be considered after biliary sphincterotomy in patients with SOD. (See “Overview of pancreatic stenting and its complications”).

The remainder of this discussion is continued elsewhere. (See “Clinical manifestations and diagnosis of sphincter of Oddi dysfunction”).

RECOMMENDATIONS — The evaluation of patients with suspected SOD should consider the availability of local expertise since the accuracy of the various diagnostic tests is highly operator dependent.

Evaluation of suspected biliary SOD — As discussed above, patients who are classified as Milwaukee Biliary Group Classification I usually respond to sphincterotomy, which can be performed without prior biliary manometry.

  • For Class II patients in whom sphincterotomy is being considered, we recommend documentation of SOD with biliary manometry. Hepatobiliary scintigraphy (in patients whose gallbladder is intact) or a fatty meal ultrasound study (in patients with or without a gallbladder) is a reasonable alternative provided that local standards for these tests have been established (show algorithm 1). On the other hand, some authorities recommend empiric sphincterotomy in such patients, a strategy that was supported by a cost-effectiveness analysis [57].
  • Patients who are classified as Milwaukee Biliary Group Classification III are commonly encountered and represent a difficult diagnostic challenge. A statement issued during the National Institutes of Health State of the Science conference on ERCP suggested that the diagnosis and management of type III SOD was the most difficult [58]. Invasive procedures should be delayed or avoided in such patients if possible. ERCP with SO manometry and endoscopic sphincterotomy should ideally be performed at specific referral centers and preferably in randomized controlled trials. Symptoms in these patients may be due to SOD or functional bowel diseases such as dyspepsia or irritable bowel syndrome. To further complicate matters, these conditions may coexist and represent generalized smooth muscle dysfunction or duodenal hyperalgesia [59]. The following recommendations apply to this group of patients.

Our approach begins with evaluation focused on detecting clinical features associated with irritable bowel syndrome or functional dyspepsia (show algorithm 1). Patients whose clinical features are more consistent with one of these diagnoses are treated accordingly. (See “Clinical manifestations and diagnosis of irritable bowel syndrome” and see “Approach to the patient with dyspepsia”).

For other patients we proceed based upon whether or not the gallbladder is intact. In patients who have not undergone cholecystectomy, we obtain a gallbladder ejection fraction to determine whether the gallbladder may be the source of symptoms. For those who have an ejection fraction <40>40 mmHg in all three recording channels). Criteria for SO “dyskinesia” included: an increased incidence of phasic SO contractions (>7/min), an increased incidence of retrograde propagated SO phasic contractions (>50 percent) and a paradoxical contraction response of the SO to cholecystokinin octapeptide bolus injection. So manometry was repeated at three and 24 months. A clinician unaware of the results of manometry or randomization followed the patients for two years.

Twenty-six of the 81 patients (32 percent) had SO stenosis based upon the manometric results. In the SO stenosis group (predominantly Type II patients) 11 of 12 (85 percent) showed long-term improvement after sphincterotomy. In contrast, in the sham group with stenosis only 5 of 13 patients (30 percent) improved, an insignificant number. The other manometric categories (SO normal and SO dyskinesia) showed no significant improvement.

Recurrent pancreatitis — The benefit of endoscopic pancreatic sphincterotomy for patients with pancreatitis thought to be related to SOD was evaluated in a series of 160 patients, of whom 64 percent had complete and long-lasting resolution of symptoms [20]. Some patients required repeat sphincterotomy for recurrent SO stenosis.

Pancreatitis is a potential complication of sphincterotomy. The risk may be greater after pancreatic than biliary sphincterotomy and most often occurs in patients with pancreatic sphincter hypertension [21]. Placement of a pancreatic stent following biliary sphincterotomy may reduce the incidence of pancreatitis in these patients. This was illustrated in a prospective, randomized, controlled trial of 80 patients with manometrically proven pancreatic sphincter hypertension; stenting of the pancreatic SO segment after biliary sphincterotomy significantly reduced the risk of pancreatitis (7 versus 26 percent with no stenting) [22]. Patients who did not receive a stent were significantly more likely to develop pancreatitis if their pancreatic duct was not patent (33 versus 0 percent), supporting the hypothesis that adequate drainage of the pancreas is necessary to prevent pancreatitis following sphincterotomy. (See “Overview of pancreatic stenting and its complications”).

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 [20].

Surgical sphincterotomy for recurrent pancreatitis is associated with worse outcomes than for recurrent biliary pain (see below). A possible explanation is that patients with recurrent pancreatitis have developed irreversible structural pancreatic disease that does not improve after sphincterotomy. Although this observation has not been proven for endoscopic pancreatic sphincterotomy, it also probably applies.

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 [23]. 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:

It is difficult to sever the transampullary septum during conventional endoscopic sphincterotomy without risking duodenal perforation. As a result, endoscopic sphincterotomy may not completely relieve pancreatic duct obstruction [24]. Endoscopic sphincterotomy of the biliary segment of the SO may not effect the pancreatic duct segment at all [25].
Surgery may reduce the chance of recurrent stenosis due to scarring.
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.

Improvement in biliary pain and recurrent pancreatitis have been demonstrated in approximately 50 to 60 percent of patients treated by surgical sphincterotomy [26-32]. However, surgical sphincterotomy and septoplasty for pancreatitis may be associated with worse outcomes than for recurrent biliary pain [32]. 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 [30].

Published in: Medicine on July 28th, 2006


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