ROME FOUNDATION DIAGNOSTIC ALGORITHMS
GB AND SPHINCTER OF ODDI DISORDERS
Gallbladder and Sphincter of Oddi Disorders
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764
nature publishing group
Enrico S. Corazziari, MD1 and Peter B. Cotton, MD, FRCP, FRCS2
Am J Gastroenterol 2010; 105:764–769; doi:10.1038/ajg.2010.67
GALLBLADDER AND SPHINCTER OF ODDI SYMPTOMS
The investigation and management of patients with recurrent episodes of right upper quadrant and epigastric pain is challenging,
as there are numerous causes, both “organic” and “functional” (1).
Symptoms of functional gallbladder (GB) and sphincter disorders
must be distinguished from those due to cholelithiasis, pancreatitis, gastroesophageal reflux disease, irritable bowel syndrome,
functional dyspepsia, and peptic ulcer disease.
Biliary pain
The Rome III Committee (2) concluded that biliary (and pancreatic) pain classically occurs in recurrent episodes of steady, severe,
pain located in the epigastrium and/or the right upper abdominal
quadrant lasting ≥30 min, not relieved by bowel movements, postural changes, or antacids. In the absence of structural disease (e.g.,
gallstones, pancreatitis, or malignancy), such pains may be the clinical presentation of GB or sphincter of Oddi (SO) dysfunction.
The assumed mechanism for biliary-like pain in patients with
the GB in situ is the increased resistance to the flow of bile at the
level of the cystic duct, whereas complete obstruction produces
acute cholecystitis. An alternative and more recent explanation
is the presence of acquired and genetically determined metabolic
and neurohormonal alterations that cause poor GB contractility and result in lithogenic bile, leading to stones and cholecystitis. The assumed mechanism for biliary (pancreatic)-like pain in
patients previously submitted to cholecystectomy is the increased
resistance to bile and/or pancreatic secretion flow at the level of the
SO. Both stenosis and dyskinesia may cause obstruction to flow
through the sphincter(s), with corresponding increased pressure in
the ducts. In the case of the biliary tree, this increase is aggravated
by the absence of the GB reservoir function (2). When episodes of
pain have been recurrent, spinal cord or other central mechanisms
are also potential contributing factors to the pain, as in the other
functional gastrointestinal (GI) disorders.
A deliberate evidence-based approach is desirable to avoid mistakes of omission and commission, both of which can cause needless suffering. The purpose of these algorithms and associated notes
is to suggest a pathway through this complex maze. Unfortunately,
some of the available tests are operator dependent, and the predictive value of several (e.g., nuclear medicine studies) is controversial.
“Suspected sphincter of Oddi dysfunction” is a particularly difficult
area, where data are scarce and the risks (of endoscopic retrograde
cholangiopancreatography (ERCP) and manometry) are substantial
(3). To reduce clinical uncertainty and to limit invasiveness, patients
are traditionally subgrouped according to the presence or absence
of abnormalities on initial testing. The diagnosis of SO dysfunction is easy to entertain when patients with typical pain also have
objective findings, i.e., elevation of liver blood tests or pancreatic
enzymes and/or dilated common bile duct. Diagnostic uncertainty
is maximal when no such diagnostic clues are present. Thus, clinicians are urged to make best use of their clinical skills in advising
their patients, to use noninvasive approaches and treatment trials,
and, at all times, to make sure that patients are aware of the possible alternative approaches, and of the gaps in our knowledge in
this area. Although there is considerable overlap in the issues and
relevant approaches, in these algorithms we have chosen to separate
pre- and post-cholecystectomy contexts.
RECURRENT BILIARY-LIKE PAIN: GB IN PLACE
Case history
A 35-year-old nurse of Hispanic origin is referred to a gastroenterologist by her primary care physician because of several episodes of
severe upper abdominal pain that have occurred over a 6-month
period. When it occurs, the pain is always located in the right upper
quadrant of the abdomen, builds up to a steady and intense level, lasts
30 min to 1 h, and is of sufficient severity to disrupt her normal activities (Box 1, Figure 1). It often radiates to the right subscapular region.
She is unable to identify any definite precipitating factors to the pain,
although on two occasions, it occurred soon after her evening meal.
The pain awoke her from sleep on one occasion. On several occasions,
she has experienced diaphoresis and nausea and vomiting during the
episode of pain. The pain is not relieved by defecation or passage of
flatus (Box 2), and she reports that it is not triggered by movements or
lifting (Box 4). She has taken an antacid on two occasions during an
episode of pain but this did not improve the pain (Box 6). In between
attacks, she does not suffer from other GI symptoms apart from occasional heartburn, and her weight has been steady. The patient has no
significant medical history. She takes no regular medications and does
not smoke or drink alcohol. In her family history, the patient reports
that her mother suffered from “gallbladder trouble” that had been difficult to diagnose, but had eventually been cured by cholecystectomy.
1
Dipartimento di Scienze Cliniche Policlinico, Umberto I V. le del Policlinico, Rome, Italy; 2Medical University of South Carolina, Charleston, SC, USA. Correspondence:
Enrico S. Corazziari, MD, Dipartimento di Scienze Cliniche Policlinico, Umberto I V. le del Policlinico, Rome 00161, Italy. E-mail: enrico.corazziari@uniroma1.it
The American Journal of GASTROENTEROLOGY
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The gastroenterologist obtains further history that one attack
of severe pain had caused her to be taken to the emergency room,
where she was found to be afebrile and to have no specific abdominal abnormalities on physical examination. The discharge summary
from that hospital visit states that her white cell count was normal, as
were standard liver biochemistry and serum amylase and lipase. An
abdominal ultrasound (US) scan (Box 10) had also been performed
and was reported as unremarkable, although the quality of the images
was poor because of her body habitus and the presence of bowel gas.
A physical examination conducted by the gastroenterologist
does not reveal any specific abnormalities. Despite the apparent
lack of response to nonprescription antacids, the gastroenterologist recommends upper GI endoscopy (Box 8). This shows
no relevant abnormality. The gastroenterologist then requests
a computed tomography scan to exclude any intra-abdominal
lesion, and to obtain better images of the GB (Box 12). The
computed tomography scan is also negative, with a normalappearing GB and normal bile duct size, and normal-appearing
pancreas.
The patient continues to experience similar episodes of severe
abdominal pain, despite avoiding high-fat meals. A trial of antispasmodic therapy prescribed by her primary care physician does
not improve the pain. The patient and her mother are both convinced that the GB is causing her symptoms, and press the gastroenterologist for a surgical referral. However, the gastroenterologist
believes that further investigation is warranted; she discusses with
the patient the pros and cons of several possible additional tests
to more definitively exclude gallstone and GB disease, including
magnetic resonance cholangiopancreatography, endoscopic US of
the GB and biliary tree, and duodenal aspiration for biliary crystals (Box 12). Endoscopic US is available only at a town 50 miles
away, while the gastroenterologist is not convinced of the value of
examination for biliary crystals. After discussion, she recommends
a nuclear medicine diisopropyl iminodiacetic acid (DISIDA) scan,
to determine the ejection fraction of the GB, having confirmed that
the patient is not taking any medications that could affect the results
of the test. The investigation reports her ejection fraction to be only
20% (Box 13). On this basis, the gastroenterologist makes a diagnosis of functional GB disorder (Box 15). She suggests a 2-month
therapeutic trial with a low-dose tricyclic antidepressant agent (Box
16), but the pain episodes continue despite this. She then recommends that the patient see a biliary surgeon for consideration of
cholecystectomy (Box 17).
The surgeon had just attended a seminar, which raised doubt
on the value of the DISIDA test in this setting, as several studies
had shown little or no correlation with the outcome after cholecystectomy. However, he agrees with the gastroenterologist that the
clinical features are strong, that the family history adds some further support, and that there is no evidence for other disorders that
may explain the pain. He performs laparoscopic cholecystectomy
(Box 17) without complication. Histology of the GB reveals a mild
degree of “chronic cholecystitis.” The patient made a good recovery
and was free of symptoms when seen a year later by her internist
for a routine checkup (Box 18). Had the outcome not been satisfactory, the gastroenterologist had planned to reassess the patient for
other functional GI disorders (Box 14), and to consider the possibility of SO dysfunction (Box 19) (see the section “Post-cholecystectomy biliary-like pain” algorithm).
Figure 1. Legend
1. The typical features of biliary (and pancreatic) pain have been defined
(2) as: episodes of epigastric and/or right upper quadrant pain, lasting
≥30 min and occurring at different intervals (not daily), with the pain
building up to a steady level, and being severe enough to interrupt
the patient’s daily activities or lead to an emergency room (ER) visit. It
is important to emphasize that the following diagnostic algorithm and
discussion refers specifically to pain fulfilling all the above-mentioned
characteristics for biliary-like pain, and especially if one or more of
the additional features of the pain outlined below are present. These
additional features of the pain that should be established are: whether
the pain radiates to the back and/or to the subscapular region, and
whether the pain awakens the patient from sleep; also, whether there
is associated nausea and vomiting. Pancreatic pain is usually focused
in the epigastrium, with radiation to the mid-back.
2. Abdominal pain consistently relieved by defecation or the passage
of flatus, in the absence of alarm features, suggests a functional
bowel disorder (1). Alarm features include unintentional weight loss,
lymphadenopathy, abdominal mass, bleeding, and evidence
of anemia.
3. Further evaluation should be undertaken as appropriate; see the
“recurrent abdominal pain and disordered bowel habit” algorithm.
4. Pain precipitated by movement, coughing, or laughing suggests a
musculoskeletal origin.
5. Right upper quadrant/costal margin pain aggravated by sitting up
(Carnett’s sign) suggests costochondritis, which may respond to local
therapy.
6. Pain relieved consistently by antacids or proton pump inhibitors (PPIs)
suggests peptic ulceration or gastroesophageal reflux disease.
© 2010 by the American College of Gastroenterology
7–9.
Upper gastrointestinal (GI) endoscopy is the primary tool for
diagnosing mucosal disease of the esophagus, stomach, and duodenum. It is also usually undertaken for completeness even when
the pain is not relieved by acid suppression, but ultrasound (US)
scanning should take precedence. It must be noted that gallbladder pain and pain from other sources may coexist; hence, it may
still be appropriate to investigate further for gallbladder disease.
10,11. Abdominal US scan and relevant blood tests should be performed
initially when gallbladder disease is suspected. US has high accuracy for the detection of gallstones > 3 mm in diameter, and for
cholecystitis (4). The extent to which it can detect or exclude other
conditions (e.g., bile duct stones, pancreatitis, and pancreatic
tumors) is highly dependent on the operator, and on the size of any
lesion. When symptoms are typical and especially if there are other
pointers to gallbladder disease (e.g., transient liver test abnormalities or a strong family history), there should be no hesitation to
repeat the US scan. Liver biochemistry and serum amylase/lipase
are normal in patients with functional gallbladder disorder.
12.
With a negative US scan, or scans, of good quality, the next step
depends on the degree of continuing clinical suspicion for gallstones or gallbladder disease as opposed to other rarer conditions
(e.g., pancreatitis). In many circumstances, abdominal computed
tomography (CT) scanning will be chosen to provide a broader
survey for abdominal pathology. Good-quality CT scans can detect
most cases of active and chronic pancreatitis and pancreatic
tumors, as well as intra- and retro-peritoneal masses. Endoscopic
US (EUS) is the most sensitive test for small gallstones, bile duct
stones, and pancreatic disease, but it is not universally available,
The American Journal of GASTROENTEROLOGY
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GB AND SPHINCTER OF ODDI DISORDERS
GB and Sphincter of Oddi Disorders
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Corazziari and Cotton
1
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GB AND SPHINCTER OF ODDI DISORDERS
Patient with recurrent episodes of pain (not daily),
in the epigastrium/right upper quadrant,
lasting >30 min, building to a steady level,
interrupting activities, or ER visit
3
Assess for
functional
bowel disorder
(IBS)
13
2
yes
no
5
15
DISIDA
gallbladder
ejection fraction
<40%?
Relief by bowel
movements?
yes
Abnormal
abdominal imaging?
CT/MRCP/EUS
no
6
Assess for
acid-related
disorders
yes
no
Pain
relief?
10
Abnormal
liver tests,
amylase/lipase,
abdominal ultrasound
scan?
8
no
yes
yes
18
Consider
cholecystectomy
no
Abnormal upper
GI endoscopy?
No response to
therapeutic trials
17
Relief by
acid suppression?
no
16
Reassess for
other functional
GI disorders
no
Position related?
12
7
Functional
gallbladder disorder
14
4
Assess for
musculoskeletal
disorders
yes
no
yes
yes
19
Consider
sphincter of Oddi
dysfunction
11
9
Peptic ulcer,
gastroesophageal
reflux disease,
gastric cancer
Gallstones, bile duct stones,
pancreatitis, kidney stone,
pancreatic, hepatic, renal or
colonic tumor
Figure 1. Recurrent biliary-like pain: gallbladder in place. DISIDA, diisopropyl iminodiacetic acid.
13.
is operator dependent, and is also somewhat invasive. Magnetic
resonance (MR) scanning with MR cholangiopancreatography
(MRCP) provides good images of the abdominal organs, and both
biliary and pancreatic ductal systems (especially with secretin
infusion). It has provided an excellent risk-free alternative to ERCP,
which should be reserved for treatment of conditions detected by
noninvasive means. The extent to which these scans are used in a
particular case should depend on the clinician’s level of suspicion
for different sources of the pain. For instance, a broader search
may be appropriate in a patient aged 65 years (especially someone
who is losing weight) than would be reasonable in a fit 30-year-old
patient. Gallbladder bile can be sampled for cholesterol crystals
with duodenal aspiration after cholecystokinin (CCK) stimulation.
The finding of microlithiasis may justify cholecystectomy if there
are no confounding factors (e.g., prolonged fasting). However, this
test is cumbersome, requires small bowel intubation, is not well
standardized, and has been largely superseded by EUS.
Dynamic DISIDA gallbladder scanning (with CCK provocation)
can be used to assess gallbladder dysfunction, and is appropriate
when suspicion is high and scans are negative. An ejection fraction
of < 40% is usually considered to define abnormality. However, this
test is not standardized and may be conducted differently in different institutions. Moreover, low ejection fraction can occur in other
conditions (such as diabetes, obesity, celiac disease, and with
certain medications, such as narcotic and anticholinergic agents);
therefore, the result must be interpreted in context, and with caution. The extent to which the results predict the results of surgery
is controversial (5,6). Reproduction of pain on injection of CCK has
been considered to indicate a gallbladder disorder, but this is not a
The American Journal of GASTROENTEROLOGY
good predictor of a good surgical outcome. CCK is not universally
available for human use.
14.
Patients with comprehensive negative investigations, including
DISIDA scanning, should be reassessed carefully, especially for
other functional GI disorders. In a few cases, cholecystectomy
can still be considered, if the pain is typical and disabling, and
especially if there are other pointers, such as a strong family history
of gallbladder disease, or transient disturbances of liver enzymes.
There is no proven role for sphincter of Oddi manometry (at ERCP)
in patients with a gallbladder in place.
15–17. In this context, the diagnosis of functional gallbladder disorder is
suggested by abnormal isotope scanning of the gallbladder. The
Rome III diagnostic criteria (1) for functional gallbladder disorder
are as follows: (i) episodes of epigastric and/or right upper quadrant pain, lasting ≥30 min and occurring at different intervals (not
daily), with the pain building up to a steady level, being moderate
to severe enough to interrupt the patient’s daily activities or lead
to an ER visit, and not being relieved by bowel movements,
postural change, or antacids; (ii) exclusion of other structural
disease that would explain the symptoms; (iii) gallbladder present;
and (iv) normal liver enzymes, conjugated bilirubin, and amylase/
lipase. Supportive criteria are associated nausea and vomiting,
pain radiating to the back and/or subscapular region, and pain
awakening the patient from sleep. However, it is important to note
that an abnormal test does not exclude another overlapping functional GI disorder as being the cause of the patient’s symptoms.
For this reason, it is appropriate to give a therapeutic trial of
medication and to only consider further more invasive treatments
on a case-by-case basis. Thus, if not previously undertaken,
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an adequate therapeutic trial with an antispasmodic agent, a psychotropic agent, or other appropriate agents should be undertaken
before consideration of cholecystectomy. Lack of any symptomatic
response further supports the consideration for cholecystectomy.
As indicated above, however, clinical studies evaluating the role
of cholecystectomy in symptomatic patients without gallstones
but with positive dynamic biliary imaging have provided variable
results. One systematic review and meta-analysis found
that patients with suspected functional biliary pain with decreased
gallbladder ejection fraction did not have a better symptomatic
outcome after cholecystectomy than those with normal ejection
fraction (7). A recent systematic review, however, addressed a
different question, concluding that patients with biliary-like pain
without gallstones but with a decreased gallbladder ejection
fraction are more likely to experience symptom relief after
POST-CHOLECYSTECTOMY BILIARY-LIKE PAIN
Case history
A 46-year-old postal worker is referred to a gastroenterologist because of multiple episodes of severe right upper quadrant
abdominal pain. On three occasions at several month intervals
over the past 2 years, the pain has required emergency room visits.
Her previous medical history is negative except for a cholecystectomy performed for the removal of gallstones 8 years earlier, after
several episodes of uncomplicated biliary colic. Further analysis of the presenting pain by the gastroenterologist reveals that
it increases to a maximum level and remains steady for > 30 min
(Box 1, Figure 2). At times, the pain can radiate to the right subscapular region, and she has vomiting associated with the pain on
some occasions. The pain has not woken her from sleep. There are
no obvious precipitating factors. She has not used codeine-containing medications and the pain is not related to, or affected by,
bowel movements; the pain is not relieved by antacids, posture, or
movement (Box 2). In fact, the pain is as far as she can remember, very similar to that which she experienced before undergoing
cholecystectomy. The patient does not admit to any GI symptoms in the pain-free intervals. Physical examination is negative,
including evaluation for an abdominal wall origin of pain (Box 2).
The patient is not overweight.
Blood tests to assess serum liver biochemistry and pancreatic enzymes, and an abdominal US scan, are conducted
(Box 3). The blood tests are normal. The US does not show bile
cholecystectomy than those treated medically (8). An earlier analysis examining this question came to a similar conclusion (9). It is
clear that further prospective randomized clinical studies are
required to determine definitively the role of dynamic isotope biliary
scanning in the investigation and management of acalculous
biliary-like pain.
18.
The diagnosis of a functional gallbladder disorder is confirmed by
the relief of pain after cholecystectomy, for a period longer than
12 months.
18,19. Lack of pain relief after cholecystectomy requires reassessment,
initially to rule out a complication of surgery or residual pathology
(e.g., duct stones). If the pain remains the same as preoperatively,
diagnostic considerations would include sphincter of Oddi dysfunction (see algorithm for “post-cholecystectomy biliary-like pain”), or
a nonbiliary source, including other functional GI disorders.
duct stones (Box 4) but does show a common bile diameter of
12 mm (Box 8). At this stage, although the patient’s pain appears
most consistent with a biliary origin, the gastroenterologist wants
to exclude conditions such as gastroesophageal reflux disease
and peptic ulcer (Box 7), and therefore performs an upper GI
endoscopy (Box 6); this reveals no abnormality. The gastroenterologist considers further abdominal imaging and arranges a
magnetic resonance cholangiopancreatography. This also shows
no abnormality except for the dilated bile duct (Box 8). Computed tomography scan of the abdomen does not reveal any other
intra-abdominal abnormality (Box 9). In the absence of structural disease, the gastroenterologist suspects that the typical biliary-like pain might be due to SO dysfunction (Box 10). Records
from the patient’s previous emergency room visits reveal that her
liver biochemistry and pancreatic enzymes were normal on each
visit. On the basis of the lack of any abnormality on blood tests,
but the presence of a dilated bile duct, a diagnosis of biliary SO
dysfunction type II is made. Knowing the risks of ERCP (with or
without sphincter manometry) in such cases, the gastroenterologist refers the patient to a colleague with more experience. He
considers quantitative choledochoscintigraphy, but for this case
is not convinced by its discriminant value, and proceeds to ERCP
(Box 16). Biliary manometry is abnormal and sphincterotomy is
performed. As the pancreatic duct was injected during the cannulation process, a small temporary pancreatic stent was placed
to reduce the risk of pancreatitis.
Figure 2. Legend
1.
2.
This description of pain in patients previously submitted to cholecystectomy is considered to indicate a biliary-pancreatic origin, and
is suggestive of sphincter of Oddi dysfunction (SOD) (1). As with
the previous algorithm, it is important to emphasize that the following diagnostic algorithm and discussion refers only to pain fulfilling
all the specific features outlined.
These characteristics of pain are suggestive of other conditions
such as functional bowel disorder, acid-related disorder, or
musculoskeletal disorder (2), and should stimulate appropriate further investigation. Recurrent abdominal wall pain should
be considered. Sphincter of Oddi pain and other functional
gastrointestinal (GI) disorders can coexist; hence, it may be
© 2010 by the American College of Gastroenterology
3.
4,5.
appropriate to continue the diagnostic process according to
this algorithm.
Laboratory blood tests of liver biochemistry and pancreatic
enzymes, as well as noninvasive ultrasound (US), are performed to
assess the presence of biliary/pancreatic or liver pathology. Transient elevation of liver biochemistry and/or serum amylase/lipase
within 24 h of a pain episode may suggest SOD (or stone passage).
Trans-abdominal US may detect biliary tract pathology, such
as duct dilation and/or stones, and can detect some pancreatic lesions, leading to appropriate treatment. The sensitivity of
US in detecting common bile duct stones is low. The acceptable size of the bile duct after cholecystectomy is controversial.
The American Journal of GASTROENTEROLOGY
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GB AND SPHINCTER OF ODDI DISORDERS
GB and Sphincter of Oddi Disorders
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GB AND SPHINCTER OF ODDI DISORDERS
1
Patient with recurrent episodes of pain (not
daily), in the epigastrium/right upper
quadrant, lasting >30 min, building to a
steady level, interrupting activities or ER visit,
previous cholecystectomy
12
11
13
Abnormal liver tests
(X2) and dilated
common bile duct
SOD type I
14
Elevated pancreatic
enzymes
10
2
No relief by bowel movements,
postural change or antacis;
appropriate exclusion of chronic
abdominal wall pain
Consider sphincter
of Oddi
dysfunction (SOD)
Abnormal
abdominal
imaging?
Do liver tests, amylase/lipase,
and abdominal ultrasound scan
Consider ERCP and
sphincter of Oddi
manometry,
+/– prior dynamic
biliary imaging
19
18
8
3
SOD type II
Abnormal liver tests
(X2) or dilated bile duct
no
16
15
17
ERCP
Normal blood tests
and bile duct diameter
yes
SOD type III
or other
functional
GI disorder
no
4
6
Ultrasound
shows common
bile duct stones?
no
9
Abnormal upper
GI endoscopy?
yes
yes
Common bile duct stones,
pancreatitis,
pancreas divisum,
nonpancreaticobiliary lesion
7
5
Common bile
duct stones
Peptic ulcer disease,
gastroesophageal
reflux disease
Figure 2. Post-cholecystectomy biliary-like pain. ERCP, endoscopic retrograde cholangiopancreatography.
6,7.
8,9.
10.
Cholecystectomy itself does not increase the size, but the duct
may be enlarged because of previous pathology, and it does
increase slowly with age. The diameter of the common bile duct
on US scanning on average is < 6 mm and does not exceed
10 mm, even after cholecystectomy. Thus, a common bile duct
diameter > 10 mm is considered dilated (10).
Upper GI endoscopy is unlikely to yield relevant pathology with this
constellation of symptoms and when they are not alleviated by acid
suppression. However, it is wise to exclude reflux esophagitis and
ulcer disease, and gastric cancer, especially in older patients.
Normal US findings, or the finding of a dilated bile duct only, with or
without elevated liver biochemistry or abnormal pancreatic enzymes
assessed after the episodes of pain, are indications to further
investigate for potential structural causes with magnetic resonance cholangiopancreatography (MRCP), abdominal computed
tomography (CT) scan, and/or endoscopic US (EUS) depending on
the available resources and clinical suspicion. MRCP has 80–90%
sensitivity for the detection of common bile duct stones. EUS has
a diagnostic accuracy comparable with ERCP for the detection of
common bile duct stones, with specificity of about 85–90% and
sensitivity < 95% (11). EUS is the most sensitive imaging test for
chronic pancreatitis, which is an important consideration in the differential of unexplained pain in this context. In older patients, it may
be used to detect or exclude small tumors and intraductal papillary
mucinous neoplasm (IPMN).
The absence of structural abnormalities on these tests leads to
consideration of biliary SOD as a cause of pain. The Rome III
diagnostic criteria (1) for functional biliary sphincter of Oddi disorder
are as follows: (i) episodes of epigastric and/or right upper quadrant
pain, lasting ≥30 min and occurring at different intervals (not daily),
with the pain building up to a steady level, being moderate to
severe enough to interrupt the patient’s daily activities or lead to an
emergency room (ER) visit, and not being relieved by bowel movements, postural change, or antacids; (ii) exclusion of other structural
The American Journal of GASTROENTEROLOGY
disease that would explain the symptoms present; and (iii) normal
amylase/lipase. Supportive criteria are as follows: (i) one or more of
associated nausea and vomiting, pain radiation to the back and/or to
the subscapular region, and pain awakening the patient from sleep
and (ii) elevated serum transaminases, alkaline phosphatase, or
conjugated bilirubin temporally related to at least two pain episodes.
11–13. The concomitance of transiently abnormal liver biochemistry shortly
after at least two episodes of pain, with the finding of a dilated common bile duct, is diagnostic of biliary SOD type I, with an indication
to consider ERCP and endoscopic sphincterotomy (12).
14–16. The presence of elevated pancreatic enzymes is suggestive of
SOD, with delay in the flow of pancreatic secretion, and constitutes
an indication to consider ERCP and, in the absence of structural
alterations, to consider manometry of the biliary and, if clinically
relevant, pancreatic sphincter of Oddi.
15–17. Patients who have either a dilated bile duct, or abnormal liver
biochemistry (but not both criteria), on two or more occasions,
are classified as biliary SOD type II (12). These patients should
be investigated further, but there is little consensus on the best
approach (3). ERCP with biliary manometry was shown to be
predictive of a good outcome after biliary sphincterotomy in one
randomized trial 20 years earlier (12), and this has become the
standard practice in referral centers. However, cohort studies show
no better than 65% good outcomes with this approach, raising
questions about the value of biliary manometry, and the need to
study the pancreatic sphincter also. ERCP with manometry carries
a significant risk of post-procedure pancreatitis (reduced recently
by temporary pancreatic stent placement); hence, there have been
many attempts to develop noninvasive diagnostic tests. Evidence
for and against sphincter dysfunction can be obtained by studies
of dynamic biliary imaging. Several now obsolete methods have
been proposed, including measurement of the bile duct size
before and after a fatty meal, or after injection of cholecystokinin
(CCK) (1,13). Nuclear medicine imaging, assessing choledo-
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choscintigraphy with 15 or without (14) CCK provocation has
been reported to offer more reliable information. The optimum
method for choledochoscintigraphy, and the predictive value of the
results, remain somewhat controversial (13–17). They may guide
clinicians toward proceeding to sphincter manometry if positive,
or away from the procedure and attending to other treatments if
negative. In practice, such nuclear medicine imaging is not often
undertaken, and patients with severe symptoms and these parameters are usually referred for ERCP with sphincter manometry.
There are some proponents of intra-sphincteric injection of Botox
as a valid therapeutic trial (18). Dynamic MR scanning may have a
role in the future. The risk of causing pancreatitis by ERCP with or
CONFLICT OF INTEREST
Gurantors of the article: Rome Foundation.
Specific author contributions: Planning and writing the part
regarding biliary algorithms: Enrico Corazziari and Peter B. Cotton.
Financial support: This work was supported by a grant from the
Rome Foundation.
Potential competing interests: None.
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GB AND SPHINCTER OF ODDI DISORDERS
GB and Sphincter of Oddi Disorders