Editor: Peter B. Cotton
6. Sphincter of Oddi dysfunction
Evan L. Fogel & Stuart Sherman
Sphincter of Oddi dysfunction (SOD) refers to a motor abnormality of the sphincter of Oddi, typically resulting in a hypertonic
sphincter, and may be manifested clinically by chronic abdominal pain, pancreatitis, or abnormal liver function tests. In
this review, we discuss the classification systems typically used in SOD, as well as the epidemiology of this controversial
disease. The diagnostic criteria for SOD and appropriate evaluation of patients are reviewed. Both non-invasive and invasive
diagnostic methods are discussed. Sphincter of Oddi manometry (SOM) is the only available method to measure motor activity
directly, and is considered currently to be the diagnostic gold standard. Indications, performance and complications of this
technique are reviewed. Therapy for SOD is discussed, using an evidence-based approach.
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 . Nevertheless, SOD is commonly diagnosed and treated by physicians, most often (but not exclusively) amongst patients who
have residual or recurrent symptoms after cholecystectomy, in whom more common organic causes have been excluded . This section reviews the epidemiology and clinical presentation of SOD, as well as currently available diagnostic and therapeutic
A distinction is sometimes made between sphincter of Oddi dysfunction and true sphincter stenosis.
Sphincter of Oddi dysfunction
Sphincter of Oddi dysfunction refers to an abnormality of SO contractility. It is a benign, non-calculus 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 abnormal liver function tests. SO dyskinesia refers to a motor abnormality of the sphincter of Oddi,
which may result in a hypotonic sphincter but, more commonly, causes a hypertonic sphincter.
Sphincter of Oddi stenosis
In contrast, sphincter of Oddi stenosis refers to a structural alteration of the sphincter, probably from an inflammatory
process, with subsequent fibrosis.
Classification of SOD
Since 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. A variety of less accurate termssuch as papillary stenosis, ampullary stenosis, biliary dyskinesia, and postcholecystectomy syndromeare listed in the medical literature to describe this entity. The latter term is somewhat of a misnomer, as SOD may clearly
occur with an intact gallbladder.
In an attempt to deal with this confusion, and also to determine the appropriate utilization of SO manometry (SOM), a biliary
clinical classification system has been developed for patients with suspected SOD (HoganGeenen SOD classification system; (Fig. 1) based on clinical history, laboratory results, and endoscopic retrograde cholangiopancreatography (ERCP) findings . A pancreatic classification has also been developed, but is less commonly utilized  (Fig. 2). Both the biliary and pancreatic classification systems have been modified , making them more applicable for clinical use, as biliary and pancreatic drainage times have been abandoned.
Sphincter of Oddi dysfunction may occur in pediatric or adult patients of any age; however, patients with SOD are typically
middle-aged females . Although SOD most commonly occurs after cholecystectomy, it may be present with the gallbladder in situ. In a survey on functional gastrointestinal disorders, SOD appeared to have a significant impact on quality of life, as it
was highly associated with work absenteeism, disability, and health care use .
SOD in patients with gallbladder disease
The frequency of manometrically documented SOD in patients prior to cholecystectomy has received limited study. Guelrud and
colleagues  evaluated 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 and associates 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 . Fifty-three per cent 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%).
SOD after cholecystectomy
The frequency of diagnosing SOD in reported series varies considerably with the patient selection criteria, the definition
of SOD, and the diagnostic tools employed. In a British report, SOD was diagnosed in 41 (9%) of 451 consecutive patients being
evaluated for postcholecystectomy pain . Roberts-Thomson evaluated 431 similar patients and found SOD in 47 (11%). In a subpopulation of such patients with a normal
ERCP (except dilated ducts in 28%) and recurrent pain of more than 3 months' duration, SOD was diagnosed in 68% . Sherman and colleagues used SOM to evaluate 115 patients with pancreaticobiliary pain with and without liver function test
abnormalities . Patients with bile duct stones and tumours were excluded from analysis. Fifty-nine of 115 patients (51%) showed abnormal
basal SO pressure greater than 40 mmHg. These patients were further categorized by the HoganGeenen SOD classification system (Fig. 1). The frequency of abnormal manometry of a single sphincter segment was 86%, 55%, and 28%, for Type I, II, and III patients,
respectively. These abnormal manometric frequencies were very similar to those reported by others for Type I and Type II patients
[12,13]. In biliary Type III patients, the finding of an abnormal basal sphincter pressure has varied from 12% to 55% . As noted, patient selection factors may be one explanation for this great variability.
SOD in the biliary or pancreatic sphincter, or both
SOD can involve abnormalities in the biliary sphincter, pancreatic sphincter, or both. The true frequency of SOD therefore
depends on whether one or both sphincters are studied. Eversman and colleagues performed manometry of the biliary and pancreatic
sphincter segments in 360 patients with pancreaticobiliary pain and intact sphincters . In this large series, 19% had abnormal pancreatic sphincter basal sphincter pressure alone, 11% had abnormal biliary basal
sphincter pressure alone, and in 31%, the basal sphincter pressure was abnormal in both segments (overall frequency of sphincter
dysfunction was 61%). Among the 214 patients labelled Type III, 17%, 11%, and 31% had elevated basal sphincter pressure in
the pancreatic sphincter alone, biliary sphincter alone, or both segments, respectively (overall frequency of SOD 59%). In
the 123 Type II patients, 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 sphincter segments, respectively. Similar findings were reported by Aymerich
and colleagues . In a series of 73 patients with suspected SOD, basal pressures were normal in both segments in 19%, abnormal in both segments
in 40%, and abnormal in one segment but normal in the other in 41%. The negative predictive value of normal biliary basal
sphincter pressure in excluding SOD was 0.42; when the pancreatic basal sphincter pressure was normal, the negative predictive
value was 0.58. These two studies clearly suggest that both the bile duct and pancreatic duct must be evaluated when assessing
the sphincter by SOM.
SOD and pancreatitis
Dysfunction may occur in the pancreatic duct portion of the SO and cause recurrent pancreatitis. As noted earlier, a pancreatic
SOD classification system has been developed (Fig. 2), but it has not been widely utilized . Manometrically documented SOD has been reported in 15% to 72% of patients with recurrent pancreatitis, previously labelled
as idiopathic [5,12,16].
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 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 criteria
Recently, a symposium on functional disorders of the pancreas and biliary tree established the Rome II diagnostic criteria
 for SOD. These include episodes of severe abdominal pain located in the epigastrium and/or right upper quadrant, and all of the following: (1) symptom episodes lasting 30 min 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 typically characterized only by mild epigastric
or right upper quadrant 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
HoganGeenen SOD classification system (Fig. 1). Patients with SOD may present with typical pancreatic pain (epigastric or left upper quadrant radiating to the back) and
SOD may exist in the presence of an intact gallbladder . As the symptoms of SOD or gallbladder dysfunction cannot be reliably separated, the diagnosis of SOD is commonly made after
cholecystectomy or less frequently after gallbladder abnormalities have been excluded .
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).
Standard evaluation and treatment of other more common upper gastrointestinal conditions, such as peptic ulcer disease and
gastroesophageal reflux should be done simultaneously. In the absence of mass lesions, stones, or response to acid suppression
therapeutic trials, the suspicion for sphincter disease is increased.
Evaluation of patients with suspected SOD (i.e. patients with upper abdominal pain with characteristics suggestive of a pancreaticobiliary
origin) should be initiated with standard serum liver chemistries, serum amylase, or lipase. The serum enzyme studies should
be drawn during bouts of pain, if possible. Mild elevations (< 2 × upper limits of normal) are frequent in SOD whereas greater abnormalities are more suggestive of stones, tumours, and liver
parenchymal disease. Although the diagnostic sensitivity and specificity of abnormal serum liver chemistries are low , recent evidence suggests that the presence of abnormal liver tests in Type II biliary SOD patients may predict a favourable
response to endoscopic sphincterotomy .
CT scans and abdominal ultrasounds are usually normal but occasionally a dilated bile duct or pancreatic duct may be found
(particularly in patients with Type I SOD).
Non-invasive diagnostic methods for SOD
Because SOM (considered by most authorities to be the gold standard for diagnosing SOD) is difficult to perform, invasive,
not widely available, and associated with a relatively high complication rate, several non-invasive and provocative tests
have been designed in an attempt to identify patients with SOD.
Morphineprostigmin provocative test (Nardi test)
Morphine has been shown to cause SO contraction, as assessed manometrically. Prostigmin (neostigmine), 1 mg subcutaneously, is added as a vigorous cholinergic secretory stimulant to morphine (10 mg subcutaneously) to make this challenge test. The morphineprostigmin test, historically, had been used extensively to diagnose SOD. Reproduction of the patient's typical pain associated
with a fourfold increase in AST, ALT, alkaline phosphatase, amylase, or lipase levels constitutes a positive response. The
usefulness of this test is limited by its low sensitivity and specificity in predicting the presence of SOD and its poor correlation
with outcome after sphincter ablation . This test has largely been replaced by tests believed to be more sensitive.
Radiographic assessment of extrahepatic bile duct and main pancreatic duct diameter after secretory stimulation
Ultrasound provocation testing
After a lipid-rich meal or cholecystokinin administration, the gallbladder contracts, bile flow from the hepatocytes increases,
and the SO relaxes, resulting in bile entry into the duodenum. Similarly, after a lipid-rich meal or secretin administration,
pancreatic exocrine juice flow is stimulated and the SO relaxes. If the SO is dysfunctional and causes obstruction to flow,
the common bile duct or main pancreatic duct may dilate under secretory pressure. This can be monitored by transcutaneous
ultrasonography. Sphincter and terminal duct obstruction from other causes (stones, tumours, strictures) may similarly cause
ductal dilation and need to be excluded. Pain provocation should also be noted if present. Limited studies comparing these
non-invasive tests with SOM or outcome after sphincter ablation  show only modest correlation. Due to overlying intestinal gas, the pancreatic duct may not be visualized on standard transcutaneous
Endoscopic ultrasound monitoring
Despite the superiority of endoscopic ultrasound (EUS) in visualizing the pancreas, Catalano et al.  reported the sensitivity of secretin-stimulated EUS in detecting SOD to be only 57%.
Magnetic resonance cholangiopancreatography (MRCP) can also be performed to non-invasively monitor the pancreatic duct after
secretin stimulation. However, recent preliminary data from Devereaux and colleagues  revealed that secretin-stimulated MRCP demonstrated a diminished, rather than exaggerated, ductal dilation response in 28
patients with SOD.
Quantitative hepatobiliary scintigraphy
Hepatobiliary scintigraphy assesses bile flow through the biliary tract. Impairment to bile flow from sphincter disease, tumours,
or stones (as well as parenchymal liver disease) results in impaired radionuclide flow. The precise criteria to define a positive
(abnormal) study remain controversial, but duodenal arrival time greater than 20 min and hilum to duodenum time greater than 10 min are most widely used .
Four studies [29,3234] have shown a correlation between hepatobiliary scintigraphy and ERCP with SOM. Taking these four studies as a whole, totaling
105 patients, the overall sensitivity of hepatobiliary scintigraphy using SOM as the gold standard was 78% (range 44100%), specificity 90% (range 80100%), positive predictive value 92% (range 82100%), and negative predictive value 81% (range 62100%). However, these promising results have not been reproduced by others. Overall, it appears that patients with dilated
bile ducts and high-grade obstruction are likely to have a positive scintigraphic study. Esber and colleagues  found that patients with lower-grade obstruction (HoganGeenen classification Types II and III) generally have normal scintigraphy, even if done after cholecystokinin provocation.
Adding morphine provocation
The value of adding morphine provocation to hepatobiliary scintigraphy was recently reported . Thirty-four patients with a clinical diagnosis of Type II and Type III SOD underwent scintigraphy with and without morphine
and subsequent biliary manometry. The standard scan did not distinguish between patients with normal and abnormal SOM. However,
following provocation with morphine, there were significant differences in the time to maximal activity and the percentage
of excretion at 45 and 60 minutes. Using a cut-off value of 15% excretion at 60 min, the use of morphine during hepatobiliary scintigraphy increased the sensitivity and specificity for SOD detection to
83% and 81%, respectively.
Comparing non-invasive tests
The Milwaukee group recently reported their retrospective review of fatty-meal sonography (FMS) and hepatobiliary scintigraphy
(HBS) as potential predictors of SOD . In this study, 304 postcholecystectomy patients suspected of having SOD were evaluated by SOM, FMS, and HBS. A diagnosis
of SOD was made in 73 patients (24%) by using SOM as the reference standard. Sensitivity of FMS was 21% and HBS 49%, whereas
specificities were 97% and 78%, respectively. FMS, HBS, or both were abnormal in 90%, 50%, and 44% of patients with HoganGeenen SOD Types I, II, and III, respectively. Of the 73 patients who underwent biliary sphincterotomy, 40 had a long-term
response. Among these SOD patients, 11/13 patients (85%) with an abnormal HBS and FMS had a good long-term response. This study suggested that while non-invasive
tests are not able to predict an abnormal SOM, they may be of assistance in predicting response to sphincter ablation in SOD
Current status of non-invasive methods
In the absence of more definitive data, we conclude that use of HBS as a screening tool for SOD should not be recommended
for general clinical use. Abnormal results may be found in asymptomatic controls . Furthermore, HBS does not address the pancreatic sphincter. Use of hepatobiliary scintigraphy and other non-invasive methods
should be reserved for situations where more definitive testing (manometry) is unsuccessful or unavailable.
Invasive diagnostic methods for SOD
Because of their associated risks, invasive testing with ERCP and manometry should be reserved for patients with clinically
significant or disabling symptoms. In general, invasive assessment of patients for SOD is not recommended unless definitive
therapy (sphincter ablation) is planned if abnormal sphincter function is found.
Cholangiography is essential to rule out stones, tumours, or other obstructing processes of the biliary tree that may cause
symptoms identical to those of SOD. Once such lesions are ruled out by a good quality cholangiographic study, ducts that are
dilated or drain slowly suggest obstruction at the level of the sphincter. A variety of methods to obtain a cholangiogram
are available. For non-invasive imaging, magnetic resonance cholangiography (MRC) is most promising, but quality varies greatly
from centre to centre. Software development continues and quality of images continues to evolve. Direct cholangiography can
be obtained by percutaneous methods, intraoperative methods, or more conventionally at ERCP. Although some controversy exists,
extrahepatic ducts that are greater than 12 mm in diameter (postcholecystectomy) when corrected for magnification, are considered dilated. Drugs that affect the rate
of bile flow and relaxation or contraction of the SO influence drainage of contrast. Such drugs must be avoided to obtain
accurate drainage times. Since the extrahepatic bile duct angulates from anterior (the hilum) to posterior (the papilla),
the patient must be supine to assess gravitational drainage through the sphincter. Although definitive normal supine drainage
times have not been well defined , a postcholecystectomy biliary tree that fails to empty all contrast media by 45 min is generally considered abnormal.
Endoscopic evaluation of the papilla and peripapillary area can yield important information that can influence the diagnosis
and treatment of patients with suspected SOD. Occasionally, ampullary cancer may simulate SOD. The endoscopist should do tissue
sampling of the papilla (preferably after sphincterotomy) in suspicious cases .
Radiographic features of the pancreatic duct are also important to assess in the patient with suspected SOD. Dilation of the
pancreatic duct (> 6 mm in the pancreatic head, and > 5 mm in the body) and delayed contrast drainage time (9 minutes in the prone position) may give indirect evidence for the presence
Intraductal ultrasonography (IDUS)
Intraductal ultrasonography makes it possible to assess sphincter of Oddi morphology during endoscopy. The sphincter appears
as a thin hypoechoic circular structure on IDUS . Limited studies thus far reveal no correlation between the basal sphincter pressures (as detected at SOM) and the thickness
of the hypoechoic layer . While IDUS may provide additional information at the level of the sphincter, it cannot be used as a substitute for SOM.
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 [42,43]. The use of manometry to detect motility disorders of the SO is similar to its use in other parts of the gastrointestinal
tract. However, performance of SOM is more technically demanding and hazardous, with complication rates (pancreatitis in particular)
reported as high as 30%. Questions remain as to whether these short-term observations (two 10-minute recordings per pull-through)
reflect the 24-hour pathophysiology of the sphincter. Despite some problems, SOM is gaining more widespread clinical application.
Sphincter of Oddi manometry: technique and indications
SOM is usually performed at the time of ERCP.
All drugs that relax (anticholinergics, nitrates, calcium channel blockers, glucagon) or stimulate (narcotics, cholinergic
agents) the sphincter should be avoided for at least 812 h prior to manometry and during the manometric session. Current data indicates that benzodiazepines do not affect the sphincter
pressure and therefore are acceptable sedatives for SOM. Meperidine, at a dose of <= 1 mg/kg, does not affect the basal sphincter pressure but does alter phasic wave characteristics . Since the basal sphincter pressure is generally the only manometric criterion used to diagnose SOD and determine therapy,
it was suggested that meperidine could be used to facilitate conscious sedation for manometry. Droperidol (45) and Propofol (46) are being increasingly utilized for SOM, and it appears that these agents also do not affect the basal sphincter pressure.
However, further study is required before their routine use in SOM is recommended. If glucagon must be used to achieve cannulation,
an 815 min 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 used. 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. Whether this guidewire influences basal sphincter pressure is unknown. 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. However, a recent study in our unit found that stiffer-shafted nitinol core
guidewires used for this purpose commonly increase basal sphincter pressure by 50100%. To avoid such artifacts, such wires need to be avoided or very soft core guidewires must be used. 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 are highly recommended for pancreatic manometry (Fig. 3). Most centers prefer to perfuse the catheters at 0.25 ml/channel using a low-compliance pump. Lower perfusion rates will give accurate basal sphincter pressures, but will not give
accurate phasic wave information. A new water-perfused sleeve system, similar to that used in the lower esophageal sphincter,
awaits more definitive trial in the sphincter of Oddi . 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.
SOM requires selective cannulation of the bile duct or pancreatic duct. The duct entered can be identified by gently aspirating
on any port (Fig. 4). The appearance of yellow-coloured 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 be simply done by injecting contrast through one of the perfusion ports. Blaut and colleagues  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 catheter is not impacted against the wall of the duct to assure accurate pressure measurements. Once
deep cannulation is achieved and the patient acceptably sedated, the catheter is withdrawn across the sphincter at 12 mm intervals by standard station pull-through technique.
Study both sphincters
Ideally, both the pancreatic and bile ducts should be studied. Data indicate that an abnormal basal sphincter pressure may
be confined to one side of the sphincter in 35% to 65% of patients with abnormal manometry [5,15,4952]. Thus, one sphincter may be dysfunctional whereas the other is normal. Raddawi and colleagues  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 s 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 or appears
on the computer screen. This permits optimal positioning of the catheter to achieve interpretable tracings. Alternatively,
electronic manometry systems with a television screen can be mounted near the endoscopic image screen to permit the endoscopist
to view the manometry tracing during endoscopy. Once the baseline study is done, agents to relax or stimulate the sphincter
can be given (e.g. cholecystokinin) and manometric or pain response monitored. The value of these provocative maneuvers for
everyday use needs further study before widespread application is recommended.
Interpretation of manometry traces
Criteria for interpretation of an SO tracing are relatively standard; however, they may vary somewhat from centre to centre.
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 . Our recommended method for reading the manometry tracings is first to 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. The highest basal pressure (Fig. 5) that is sustained for at least 30 s is then identified. From the four lowest amplitude points in this zone, the mean of
these readings is taken as the basal sphincter pressure for that lead for that pull-through. The basal sphincter pressure
for all interpretable observations is then averaged; this is 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  suggest that intraductal biliary 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). This study needs to be confirmed but supports the theory that increased intrabiliary pressure is a cause of pain in
The best study establishing normal values for SOM was reported by Guelrud and associates . Fifty asymptomatic control patients were evaluated and repeated on two occasions in 10 subjects. This study established
normal values for intraductal pressure, basal sphincter pressure, and phasic wave parameters (Fig. 6). Moreover, the reproducibility of SOM was confirmed. Various authorities interchangeably use 35 mmHg or 40 mmHg as the upper limits of normal for mean basal sphincter of Oddi pressure.
Complications of SOM
Several studies have demonstrated that pancreatitis is the most common major complication after SOM . 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
is associated with a high complication rate. Rolny and associates  found that patients with chronic pancreatitis were at higher risk of postprocedure pancreatitis following pancreatic duct
manometry. They reported an 11% incidence of pancreatitis following manometric evaluation of the pancreatic duct. Twenty-six
per cent of chronic pancreatitis patients undergoing SOM developed pancreatitis.
Methods to reduce complications
A variety of methods to decrease the incidence of postmanometry pancreatitis have been proposed.
- use of an aspiration catheter
- gravity drainage of the pancreatic duct after manometry
- decrease the perfusion rate to 0.050.1 ml/lumen/min
- limit pancreatic duct manometry time to less than 2 min (or avoid pancreatic manometry)
- use the microtransducer (non-perfused) system 
- placement of pancreatic stent after manometry and/or sphincterotomy .
Aspirating catheter system
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 side ports) reduced
the frequency of pancreatic duct manometry-induced pancreatitis from 31% to 4% . The reduction in pancreatitis with the 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 the pancreatic duct sphincter is studied by SOM, aspiration of pancreatic juice and the perfusate
is strongly recommended.
In a prospective randomized trial, Tarnasky and colleagues showed that stenting the pancreatic duct decreased post-ERCP pancreatitis
from 26% to 6% in a group of patients with pancreatic sphincter hypertension undergoing biliary sphincterotomy alone .
Sphincter of Oddi manometry; conclusion
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 HoganGeenen SOD classification system (Fig. 1).
Type I patients
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.
Type II patients
Type II patients demonstrate SO motor dysfunction in 5065% of cases. In this group of patients, SOM is highly recommended as the results of the study predict outcome from sphincter
Type III patients
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.
Therapy for sphincter of Oddi dysfunction
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 . Historically, 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 HoganGeenen 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 [63,64].
Medical therapy for documented or suspected SOD has received only limited study. As 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
Khuroo and colleagues  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 and associates  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 . 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 (although 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.
Electrical nerve stimulation
Guelrud and colleagues have demonstrated 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 . Its role in the management of SOD has not been investigated.
Historically, 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 70% of patients were reported to have
benefited from this therapy during a 1- to 10-year follow-up [70,71]. 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 . Some reports have suggested that patients with biliary-type pain have a better outcome than patients with idiopathic pancreatitis,
whereas others suggested no difference [70,71]. However, most studies found that symptom improvement following surgical sphincter ablation alone was relatively uncommon
in patients with established chronic pancreatitis .
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 favour an initial endoscopic approach. At present, surgical therapy
is reserved for patients with restenosis following endoscopic sphincterotomy and when endoscopic evaluation or therapy is
not available or technically feasible (e.g. Roux-en-Y gastrojejunostomy). In many centres, however, operative therapy continues
to be the standard treatment of pancreatic sphincter hypertension [6,72].
Endoscopic balloon dilation and biliary stent trials
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
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 evaluation. 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 [59,60]. Goff reported a biliary stent trial in 21 Type II and III SOD patients with normal biliary manometry . Stents (7 French) 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. Due to this high complication rate,
biliary stent trials are strongly discouraged. Rolny and colleagues also reported a series of bile duct stent placement as
a predictor of outcome following biliary sphincterotomy in 23 postcholecystectomy patients (7 Type II and 16 Type III) . Similar to the study by Goff , resolution of pain during at least 12 weeks of stenting predicted a favourable outcome from sphincterotomy irrespective
of SO pressure. In this series, there were no complications related to stent placement.
Endoscopic sphincterotomy is the 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% to 95% of patients
(Fig. 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  studied 17 Type I postcholecystectomy biliary patients by SOM (Fig. 7). 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 centre. In contrast, results of several non-randomized controlled trials [13,17,74,75] suggest that performance of SOM is highly recommended in biliary Type II and Type III patients, as clinical benefit is less
certain (Fig. 8).
Although most of the studies reporting efficacy of endoscopic therapy in SOD have been retrospective, three notable randomized
trials have been reported.
Randomized controlled trials of endoscopic sphincterotomy for SOD
In a landmark study by Geenen and associates , 47 postcholecystectomy 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% to 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. Confirming data was seen in a 2-year follow up study by Toouli et al. [77,78]. In this study, postcholecystectomy patients with biliary-type pain (mostly Type II) were prospectively randomized to endoscopic
sphincterotomy or sham following stratification according to SOM. Eighty-five per cent (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).
Sherman and associates  reported their preliminary results of a randomized study comparing endoscopic sphincterotomy and 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 in Fig. 9. During a 3-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 patients (13/16, 81%, vs. 11/19, 58%; P= 0.14).
Is pancreatic sphincterotomy necessary?
Evidence is now accumulating that the addition of a pancreatic sphincterotomy to an endoscopic biliary sphincterotomy in such
patients may improve the outcome, as preliminarily reported by Guelrud et al. . Soffer and Johlin reported that 25 of 26 patients (mostly Type II), who failed to respond to biliary sphincterotomy, had
elevated pancreatic sphincter pressure . Pancreatic sphincter therapy was performed with overall symptomatic improvement in two-thirds of patients. Eversman and
colleagues found that 90% of patients with persistent pain or pancreatitis after biliary sphincterotomy had residual abnormal
pancreatic basal pressure . Five-year follow-up data revealed that patients with untreated pancreatic sphincter hypertension were much less likely to
improve after biliary sphincterotomy than patients with isolated biliary sphincter hypertension (Fig. 10). Elton et al.  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. Kaw and colleagues
 presented preliminary data demonstrating that response to sphincterotomy also depends on treating the diseased sphincter
segment. Patients with pancreatic sphincter hypertension who fail to respond to biliary sphincterotomy can be 'rescued' by undergoing pancreatic sphincterotomy (Fig. 11). Recent preliminary data from our unit examined the outcome of endoscopic therapy in SOD patients with initial pancreatic
sphincter hypertension (with or without biliary sphincter hypertension). Patients were followed for a mean of 45.3 months
(range 1177 months); re-intervention was offered for sustained or recurrent symptoms at a mean of 14.3 months following initial therapy.
Performance of an initial dual pancreaticobiliary sphincterotomy was associated with a lower re-intervention rate (69/284, 24.3%) than biliary sphincterotomy alone (31/95, 33%; P < 0.05). Confirmatory outcome studies, preferably in randomized trials, are awaited.
Risks and benefits of endoscopic treatment for SOD
These results clearly indicate that the response rate and enthusiasm for sphincter ablation must be correlated with patient
presentation and results of manometry 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 two to five
times higher than patients undergoing endoscopic sphincterotomy for ductal stones [63,64]. Pancreatitis is the most common complication, occurring in up to 30% of patients in some series. A recent prospective, multicenter
study examining risk factors for post-ERCP pancreatitis identified suspected SOD as an independent factor by multivariate
analysis . A suspicion of SOD tripled the risk of postprocedure pancreatitis to a frequency (23%) that was comparable to that found
in other recent prospective studies [58,64,8688]. Endoscopic techniques are being developed (e.g. pancreatic duct stenting prior to combined pancreaticobiliary sphincterotomy)
to limit such complications [58,89].
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, toxin injection
into the SO resulted in a 50% reduction in the basal biliary sphincter pressure and improved bile flow . 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. In a small series
, 22 postcholecystectomy Type III patients with manometric evidence of SOD underwent Botox injection into the intraduodenal
sphincter segment. Eleven of the 12 patients who responded to botulinum toxin injection later benefited from endoscopic sphincterotomy,
while only 2 of 10 patients who did not benefit from Botox injection later responded to sphincter ablation. Such an approach,
however, does require two endoscopies to achieve symptom relief. Further studies are needed before recommending this technique.
Sphincter of Oddi dysfunction in recurrent pancreatitis
Disorders of the pancreatic sphincter may give rise to unexplained (idiopathic) pancreatitis or episodic pain suggestive of
a pancreatic origin . SOD has been manometrically documented in 15% to 72% of patients with recurrent pancreatitis, previously labelled as idiopathic
[5,14,16,93]. 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  that will similarly respond to biliary sphincterotomy.
Endoscopic sphincterotomy for SOD in pancreatitis
Lans and colleagues
The value of ERCP, SOM, and sphincter ablation therapy was studied in 51 patients with idiopathic pancreatitis . Twenty-four (47.1%) had an elevated basal sphincter pressure. Thirty were treated by biliary sphincterotomy (n = 20), or surgical sphincteroplasty with 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).
Guelrud and colleagues
Guelrud and colleagues  by contrast found that severance of the pancreatic sphincter was necessary to resolve the pancreatitis (Fig. 12). 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 per cent 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 and colleagues  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
Kaw and Brodmerkel
Kaw and Brodmerkel  recently reported that among patients with idiopathic pancreatitis secondary to SOD, 78% had persistent manometric evidence
of pancreatic sphincter hypertension despite a biliary sphincterotomy.
Toouli and colleagues
Toouli and colleagues  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 9105 months).
Okolo and colleagues
Okolo and colleagues  retrospectively evaluated the long-term results of endoscopic pancreatic sphincterotomy in 55 patients with manometrically
documented or presumed pancreatic sphincter hypertension (presumption based on recurrent pancreatitis with pancreatic duct
dilation and contrast medium drainage time from the pancreatic duct greater than 10 min). During a median follow-up of 16 months (range 352 months), 34 patients (62%) reported significant pain improvement. Patients with normal pancreatograms were more likely
to respond to therapy than those with pancreatographic evidence of chronic pancreatitis (73% vs. 58%).
Endoscopic sphincterotomy as a cause of pancreatic sphincter stenosis
Jacob and colleagues  postulated that SOD might cause recurrent episodes of pancreatitis, even though SOM was normal, and pancreatic stent placement
might prevent further attacks. In a randomized study, 34 patients with unexplained recurrent pancreatitis and normal pancreatic
SOM were treated with pancreatic stents (n = 19; 57 french guage, with stents exchanged 3 times over a 1-year period) or conservative therapy. During a 3-year follow-up, pancreatitis
recurred in 53% of the patients in the control group and only 11% of the stented patients (P < 0.02). This study suggests that SOM may be an imperfect test, as patients may have SOD but not be detected at the time of
SOM. However, long-term studies are needed to evaluate the outcome after removal of stents, and concern remains regarding
stent-induced ductal and parenchymal changes [59,60,99].
Endoscopic Botox injection
Wehrmann and colleagues  recently evaluated the feasibility and effectiveness of botulinum toxin injection in patients with recurrent pancreatitis
due to pancreatic sphincter hypertension. No side-effects of the injection were noted in any of the 15 treated patients. Twelve
patients (80%) remained asymptomatic at 3-month follow-up, but 11 developed a relapse at a follow-up period of 6 ± 2 months. These 11 patients underwent pancreatic or combined pancreaticobiliary sphincterotomy with subsequent remission after
a median follow-up of 15 months. This study showed that injection of botulinum toxin is safe and may be effective short term,
but the need for definitive sphincter ablation in the majority of patients limits its clinical use.
SOD in recurrent pancreatitis: conclusion
Currently, establishing the best method of treating 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 re-evaluated and be considered for sphincter ablation if residual high pressure is found.
Our knowledge of SOD, and manometric techniques to assist in this diagnosis, is 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 owing 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 riskbenefit ratio with individual patients is mandatory.
Outstanding issues and future trends
Our hopes for the future in this evolving field are to:
- Define the role, if any, of non-invasive imaging studies as a screening test and predictor of outcome from sphincter ablation
- Develop techniques to improve the safety of the procedures used to evaluate and treat patients with pancreaticobiliary pain
- Develop a device for longer-term SOM such as a 24-hour SO manometry probe
- Define predictors of good and poor outcome from therapy to better select patients for 'risky' interventions
- Further investigate the role of pancreatic sphincterotomy for improving outcomes
- Develop more long-term outcome studies, particularly in Type II and III patients
- Explore better medical therapy alternatives for less disabled patients.
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