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GUIDELINE
The role of endoscopy in the evaluation of suspected
choledocholithiasis
This is one of a series of statements discussing the use
of GI endoscopy in common clinical situations. The Stan-
dards of Practice Committee of the American Society for
Gastrointestinal Endoscopy prepared this text. In prepar-
ing this guideline, a search of the medical literature was
performed by using PubMed. Additional references were
obtained from the bibliographies of the identified articles
and from recommendations of expert consultants. When
few or no data exist from well-designed prospective trials,
emphasis is given to results of large series and reports
from recognized experts. Guidelines for appropriate
use of endoscopy are based on a critical review of the
available data and expert consensus at the time that
the guidelines are drafted. Further controlled clinical
studies may be needed to clarify aspects of this guideline.
This guideline may be revised as necessary to account for
changes in technology, new data, or other aspects of clin-
ical practice. The recommendations were based on
reviewed studies and were graded on the strength of
the supporting evidence (Table 1).1
This guideline is intended to be an educational device
to provide information that may assist endoscopists in
providing care to patients. This guideline is not a rule
and should not be construed as establishing a legal stan-
dard of care or as encouraging, advocating, requiring,
or discouraging any particular treatment. Clinical deci-
sions in any particular case involve a complex analysis
of the patient’s condition and available courses of
action. Therefore, clinical considerations may lead an
endoscopist to take a course of action that varies from
these guidelines.
Gallstone disease affects more than 20 million Ameri-
can adults2
at an annual cost of $6.2 billion.3
A subset of
these patients will also have choledocholithiasis, including
5% to 10% of those undergoing laparoscopic cholecystec-
tomy for symptomatic cholelithiasis4-7
and 18% to 33% of
patients with acute biliary pancreatitis.8-11
The approach
to patients with suspected choledocholithiasis requires
careful consideration because missed common bile duct
(CBD) stones pose a risk of recurrent symptoms, pancre-
atitis, and cholangitis. However, the morbidity and cost
from indiscriminant and/or invasive biliary evaluation
should also be minimized. This guideline addresses the
role of endoscopy in patients with suspected
choledocholithiasis.
INITIAL EVALUATION
Choledocholithiasis is most commonly suspected in the
scenarios of symptomatic cholelithiasis and acute biliary
pancreatitis (ABP), with other presentations such as de
novo bile duct stones in the postcholecystectomy patient
occurring less often. The initial evaluation of suspected
choledocholithiasis should include serum liver biochemi-
cal tests (eg, alanine aminotransferase, aspartate amino-
transferase, alkaline phosphatase, and total bilirubin)
and a transabdominal ultrasound (US) of the right upper
quadrant. Fractionation of bilirubin can be considered in
clinical scenarios in which isolated indirect hyperbilirubi-
nemia (eg, Gilbert syndrome) may be present.
Liver biochemical tests may have the most utility in
excluding the presence of CBD stones; the negative pre-
dictive value of completely normal liver biochemical test
results in a series of more than 1000 patients undergoing
laparoscopic cholecystectomy was more than 97%,
whereas the positive predictive value of any abnormal liver
biochemical test result was only 15%.12
Although other
series have reported modestly better positive predictive
values for CBD stones for abnormal bilirubin, alkaline
phosphatase, or g-glutamyl transpeptidase, these still gen-
erally range from 25% to 50%.12-15
These latter cholestatic
liver biochemical tests generally progressively increase
with the duration and severity of biliary obstruction. As
such, more abnormally elevated values will result in an
increased likelihood of CBD stones.13,14
For example, in
one study, a bilirubin level of 1.7 mg/dL or higher por-
tended a specificity of 60% for choledocholithiasis,
whereas the specificity increased to approximately 75%
at a cutoff of 4 mg/dL.13
However, the mean bilirubin level
in series of patients with choledocholithiasis has been re-
ported at 1.5 to 1.9 mg/dL,14,15
and only a minority (one
third or less) of patients with choledocholithiasis will
have a bilirubin level of 4 mg/dL or higher.13,14
Transabdominal US has a relatively poor sensitivity (22%-
55%) for detecting CBD stones.16-19
However, US more
reliably detects dilation of the CBD (sensitivity 77%-87%),
a finding often associated with choledocholithiasis.20-23
Copyright ª 2010 by the American Society for Gastrointestinal Endoscopy
0016-5107/$36.00
doi:10.1016/j.gie.2009.09.041
www.giejournal.org Volume 71, No. 1 : 2010 GASTROINTESTINAL ENDOSCOPY 1
The normal bile duct diameter is 3 to 6 mm,24-26
and mild
dilation related to advancing age has been reported.26
Bili-
ary dilation greater than 8 mm in a patient with an intact
gallbladder is usually indicative of biliary obstruction.21
Also, the sonographic characterization of gallbladder stones
harbors some predictive value for choledocholithiasis, with
multiple small (!5 mm) stones posing a 4-fold higher risk
of migration into the duct as opposed to larger and/or sol-
itary stones.27
Given the relatively low prevalence (5%-10%)
of choledocholithiasis in patients with symptomatic chole-
lithiasis, a normal bile duct US has a 95% to 96% negative
predictive value.12,28
Thus, although no single variable consistently strongly
predicts choledocholithiasis in patients with symptomatic
cholelithiasis, many investigators have noted that the
probability of a CBD stone is higher in the presence of
multiple abnormal prognostic signs.13,29,30
As a result,
a number of different prognostic scores, formulas, and
algorithms have been devised to help predict the probabil-
ity of choledocholithiasis.13,14,29,31,32
Although there is no
single accepted scoring system, by using factors such as
age, liver test results, and US findings, patients can gener-
ally be categorized into low (!10%), intermediate (10%-
50%), and high (O50%) probability of choledocholithiasis
(Table 2). A CBD stone seen on US is the most reliable
predictor of choledocholithiasis at subsequent endoscopic
retrograde cholangiography (ERC) or surgery.13,31
The
specificity of US for CBD stones is very high, with occa-
sional discrepancies attributed to interval stone migration
or falsely positive US findings. Otherwise, the most predic-
tive variables seem to be cholangitis, a bilirubin level
higher than 1.7 mg/dL, and a dilated CBD on US. The pres-
ence of 2 or more of these variables results in a high prob-
ability of a CBD stone.13,31
Advanced age (older than 55
years), elevation of a liver biochemical test result other
than bilirubin, and pancreatitis are less robust predictors
for choledocholithiasis.13,31
Conversely, nonjaundiced
patients with a normal bile duct on US have a low proba-
bility (!5%) of choledocholithiasis.12,28
A RISK-STRATIFIED DIAGNOSTIC APPROACH
TO PATIENTS WITH SYMPTOMATIC
CHOLELITHIASIS
A proposed strategy to assign risk of choledocholithia-
sis based on clinical predictors evident after initial diag-
nostic evaluation is presented in Table 2. This table
summarizes the relative importance of common clinical
predictors for choledocholithiasis based on the available
TABLE 1. GRADE system for rating the quality of
evidence for guidelines
Quality of
evidence Definition Symbol
High quality Further research is very
unlikely to change our
confidence in the
estimate of effect.
4444
Moderate quality Further research is likely
to have an important
impact on our confidence
in the estimate of effect
and may change the
estimate.
444B
Low quality Further research is very
likely to have an important
impact on our confidence
in the estimate of effect
and is likely to change the
estimate.
44BB
Very low quality Any estimate of effect is
very uncertain.
44BB
Weaker recommendations are indicated by phrases such as ‘‘we
suggest,’’ whereas stronger recommendations are typically stated
as ‘‘we recommend.’’
Adapted from Guyatt et al.1
TABLE 2. A proposed strategy to assign risk of
choledocholithiasis in patients with symptomatic
cholelithiasis based on clinical predictors
Predictors of choledocholithiasis13,14,29,31,32
Very strong
CBD stone on transabdominal US
Clinical ascending cholangitis
Bilirubin O4 mg/dL
Strong
Dilated CBD on US (O6 mm with
gallbladder in situ)
Bilirubin level 1.8-4 mg/dL
Moderate
Abnormal liver biochemical test other
than bilirubin
Age older than 55 y
Clinical gallstone pancreatitis
Assigning a likelihood of choledocholithiasis
based on clinical predictors12-14,28,29,31,32
Presence of any very strong predictor High
Presence of both strong predictors High
No predictors present Low
All other patients Intermediate
CBD, Common bile duct.
The role of endoscopy in the evaluation of suspected choledocholithiasis
2 GASTROINTESTINAL ENDOSCOPY Volume 71, No. 1 : 2010 www.giejournal.org
literature; however, it is not a validated clinical decision
aid. A suggested management algorithm for patients
with symptomatic cholelithiasis, based on whether they
are at low, intermediate, or high probability of choledo-
cholithiasis, is presented in Figure 1.
Low risk of choledocholithiasis
Patients with symptomatic cholelithiasis who are candi-
dates for surgery and have a low probability of choledo-
cholithiasis (!10%) should undergo cholecystectomy;
no further evaluation is recommended because the cost
and risks of additional preoperative biliary evaluation are
not justified by the low probability of a CBD stone.12,28
Whether routine intraoperative cholangiography (IOC)
or laparoscopic US should be performed at laparoscopic
cholecystectomy, for purposes of both defining the biliary
anatomy and for screening for CBD stones, is an area of
controversy in the surgical literature.33-36
Intermediate risk of choledocholithiasis
Patients at intermediate probability of choledocholithia-
sis (10%-50%) after initial evaluation benefit from addi-
tional biliary imaging to further triage the need for ductal
stone clearance.28,37,38
Failure to identify CBD stones can
result in recurrent symptoms, cholangitis, and ABP.39,40
Options for evaluation of these patients include endoscopic
ultrasound (EUS), magnetic resonance cholangiography
(MRC), preoperative ERC, and IOC or laparoscopic US to
facilitate either removal at surgery or postoperative ERC.
High risk of choledocholithiasis
Patients at high probability of CBD stones (O50%)
require further evaluation of the bile duct; because of the
frequent need for therapy, typically preoperative ERC or op-
erative cholangiography are undertaken. In the era of open
cholecystectomy, there was no advantage found for preop-
erative ERC over operative cholangiography and common
duct exploration in randomized, controlled trials.41
Figure 1. A suggested management algorithm for patients with symptomatic cholelithiasis based on the degree of probability for choledocholithiasis.
Modified from Tse et al.32
The role of endoscopy in the evaluation of suspected choledocholithiasis
www.giejournal.org Volume 71, No. 1 : 2010 GASTROINTESTINAL ENDOSCOPY 3
However, open cholecystectomy is now infrequently
performed given the attenuated morbidity and shorter hos-
pital stays associated with laparoscopic cholecystectomy.
Two randomized, controlled trials compared 2-stage man-
agement (preoperative ERC followed by laparoscopic cho-
lecystectomy) with an all-surgical approach of laparoscopic
IOC and transcystic stone removal or laparoscopic choledo-
chotomy for patients at high risk of choledocholithiasis.42,43
In these studies, there was no difference in morbidity, mor-
tality, or primary ductal clearance rates (88%) between the 2
arms. Other potential options include intraoperative or
postoperative ERC for patients with positive IOC findings;
laparoscopic antegrade placement of a transpapillary stent
to ensure biliary access at postoperative ERC may also be
considered.44
A more robust discussion of operative versus
endoscopic management of choledocholithiasis in patients
undergoing cholecystectomy is beyond the scope of this
guideline. However, CBD stone detection and subsequent
management are inseparably linked, and many of the tech-
niques used for biliary evaluation and CBD stone removal
are considerably operator dependent. Thus, the best strat-
egies for the evaluation and management of choledocholi-
thiasis in patients with symptomatic cholelithiasis will
be heavily predicated on local expertise and available
technology.
Nonendoscopic biliary imaging modalities
CT: Conventional (nonhelical) CT has historically dem-
onstrated better sensitivity for choledocholithiasis than
transabdominal US when composite diagnostic criteria
are used (eg, the inclusion of indirect signs such as ductal
dilation), although direct visualization of stones has not
exceeded 75%.45
Helical CT has shown improved perfor-
mance over conventional CT for choledocholithiasis, with
65% to 88% sensitivity and 73% to 97% specificity.46-49
Expense and radiation exposure have limited the use of
CT as a first-line diagnostic test for choledocholithiasis,
but in many instances, abdominal CT scans are ordered
in the emergency department setting to evaluate and
exclude competing potential diagnoses that may have sim-
ilar presentations.
MRC: MRC has 85% to 92% sensitivity and 93% to 97%
specificity for choledocholithiasis detection, as assessed in
2 recent systematic reviews.50,51
However, the sensitivity
of MRC seems to diminish in the setting of small
(!6 mm) stones and has been reported as 33% to 71%
in this clinical subset.52-54
CT cholangiography: CT cholangiography is per-
formed by using helical CT in conjunction with a dedicated
cholegraphic iodinated contrast agent that is taken up by
the liver and excreted into the bile. Although its perfor-
mance characteristics for choledocholithiasis detection
are similar to those of MRC,46,55,56
concerns regarding
the toxicity of available cholegraphic agents and significant
radiation dose have limited the clinical adoption of this
imaging modality.
IOC: Intraoperative fluorocholangiography may be
performed by insertion of small catheter into a cystic
ductotomy or via the gallbladder (cholecystocholangiogra-
phy) and injection of iodinated contrast dye with real-time
fluoroscopic interpretation by the surgeon. IOC can be
successfully completed in 88% to 100% of patients, has
a reported sensitivity of 59% to 100% and specificity of
93% to 100% for choledocholithiasis, and typically requires
between 10 and 17 minutes to complete during a laparo-
scopic cholecystectomy.57
Laparoscopic US: Laparoscopic US transducers are
available in a variety of viewing arrays, may be rigid or flex-
ible, and fit through a conventional laparoscopic trocar.
Laparoscopic US of the extrahepatic bile duct can be suc-
cessfully completed in 88% to 100% of patients and can be
performed in 4 to 10 minutes, with a reported sensitivity
of 71% to 100% and specificity of 96% to 100%.57
Laparo-
scopic US has a reportedly longer learning curve than
does IOC.
Endoscopic biliary imaging modalities
EUS: EUS combines endoscopic visualization with
2-dimensional US and is well suited for biliary imaging
given the close proximity of the extrahepatic bile duct to
the proximal duodenum. Radial array echoendoscopes
more frequently allow elongated views of the bile duct
and are thus preferred by many endosonographers;
however, the performance of linear array instruments for
choledocholithiasis is also excellent, with series reporting
a sensitivity of 93% to 97%.58,59
Two meta-analyses, each
composed of more than 25 trials and more than 2500 pa-
tients, reported an 89% to 94% sensitivity and 94% to 95%
specificity of EUS for detecting choledocholithiasis, with
ERC, IOC, or surgical exploration used as criterion stan-
dards.60,61
EUS remains highly sensitive for stones smaller
than 5 mm, and its performance does not seem adversely
affected by decreasing stone size.62-64
Excluding examina-
tions for esophageal cancer staging, complications with
diagnostic EUS are rare (0.1%-0.3%).65-67
ERC: Because the risk of adverse events is higher with
ERC than with noninvasive biliary imaging studies or EUS,
the use of ERC as a diagnostic modality is best suited for
those patients at high risk of choledocholithiasis because
they are most likely to benefit from the therapeutic capa-
bility of ERC. ERC has traditionally served as a criterion
standard for choledocholithiasis detection; thus, data re-
garding its operating characteristics are limited. However,
the sensitivity of ERC with cholangiography alone has
been reported as 89% to 93% with a specificity of 100%
in studies that used subsequent biliary sphincterotomy
and duct sweeping with balloons/baskets as the criterion
standard.68,69
False-negative ERC findings for choledocho-
lithiasis typically occur in the setting of small stones in
a dilated duct.
The risks of ERC include pancreatitis (1.3%-6.7%),
infection (0.6%-5.0%), hemorrhage (0.3%-2.0%), and
The role of endoscopy in the evaluation of suspected choledocholithiasis
4 GASTROINTESTINAL ENDOSCOPY Volume 71, No. 1 : 2010 www.giejournal.org
perforation (0.1%-1.1%) in prospective series of unse-
lected patients.70-76
However, several patient variables
(eg, young age, female sex) have been identified that serve
as risk factors for pancreatitis; similarly, coagulopathy
increases bleeding risk and immunosuppression increases
the risk of infection at ERC.72
Thus, risk estimates must be
individualized to the patient.
ERC-associated technologies: Small-caliber, high-
frequency (12-30 MHz) wire-guided intraductal US
(IDUS) probes can be passed through the instrument
channel of a duodenoscope and into the bile duct without
a previous sphincterotomy in nearly 100% of cases.69,77
IDUS has demonstrated excellent sensitivity (97%-100%)
for choledocholithiasis,69,77
and some studies have shown
modestly improved accuracy of ERC with IDUS for stone
detection compared with cholangiography alone.77
How-
ever, the clinical impact of the high sensitivity of IDUS
for choledocholithiasis is uncertain because stones missed
by ERC that are detected by IDUS tend to be small
(!4 mm) and of unclear significance.69
Conventional ‘‘mother-daughter’’ or newer single-oper-
ator cholangioscopy systems are most often used in the
diagnosis of indeterminate biliary strictures and as an
adjunct in the management of complicated stone disease,
but may have a role in biliary stone detection in limited
settings. Adherent or impacted stones may be difficult to
differentiate from complex strictures or biliary polyps,
and direct visualization has been valuable in characterizing
these indeterminate filling defects.78
Others have re-
ported a potential role for cholangioscopy in confirming
ductal clearance in patients after stone extraction.79,80
Although they are potentially useful in specific clinical set-
tings, given the additional time and expense incurred by
IDUS and cholangioscopy, their overall role in the diagno-
sis of choledocholithiasis remains limited.
EUS-directed ERC
Given the higher morbidity of ERC compared with EUS,
several investigators recently evaluated sequential EUS
and ERC in patients with suspected choledocholithiasis
in an effort to better triage patients in need of treat-
ment.81-84
These 4 trials randomized patients at intermedi-
ate to high risk for choledocholithiasis to an EUS-first
strategy versus an ERC-first strategy. Patients found to
have CBD stones at EUS underwent subsequent therapeu-
tic ERC, which was performed in the same setting in 3 of
the 4 trials.81,83,84
Across the trials, 27% to 40% of patients
randomized to EUS were found to have CBD stones, and
the negative predictive value of EUS seemed to be robust,
with only 0% to 4% of patients with normal EUS findings
returning with pancreaticobiliary symptoms in 1 to 2 years
of follow-up. Thus, this sequential approach in these stud-
ies eliminated the need for 60% to 73% of ERC and its
attendant risk. There was either less morbidity or a trend
toward less morbidity associated with the EUS-first strat-
egy across all studies.
An EUS-guided diagnostic strategy also seems to be
cost-effective for many patients with suspected choledo-
cholithiasis. In a cost analysis associated with a prospective
trial of EUS for suspected choledocholithiasis in more
than 450 patients, an EUS-first strategy was cost-effective
for patients with an estimated likelihood of CBD stones
of less than 61%, with the ERC-first strategy proving the
dominant strategy for patients at higher risk.85
Similarly,
a decision analysis assessing the roles of IOC, ERC, and
EUS in patients undergoing laparoscopic cholecystectomy
found EUS to be cost-effective when the estimated risk of
CBD stones was 11% to 55%.37
In both of these cost anal-
yses, EUS and subsequent therapeutic ERC were per-
formed on separate days; procedures performed in
tandem with a single sedation may yield even greater
savings.
The role of endoscopy for suspected
choledocholithiasis in the
postcholecystectomy patient
Choledocholithiasis after cholecystectomy may result
from either a migrated gallbladder stone not detected in
the perioperative period or a stone forming de novo in
the common bile duct. Diagnostic considerations are
slightly different in these patients than in those with a gall-
bladder in situ. Although patients presenting with pain,
abnormal liver biochemical tests, jaundice, or fever may
have choledocholithiasis, alternative processes such as
bile leak, iatrogenic biliary stricture, and biliary-type
sphincter of Oddi dysfunction are additional possibilities
in the postcholecystectomy patient.
Generally, the initial evaluation of these patients should
include serum liver biochemical tests and a transabdominal
US, mirroring the approach to the precholecystectomy
patient with symptomatic cholelithiasis. However, dilation
of the common bile duct after cholecystectomy has been
reported,86,87
so using a 6-mm cutoff for normal is likely
not appropriate for this population. Also, some patients
reporting postcholecystectomy pain may have chronic
abdominal pain unrelated to their biliary tree, and thus
unresolved by cholecystectomy. In these patients, use of
narcotic analgesics is not uncommon, and biliary dilation
related to narcotic use has also been reported.88,89
Data regarding the evaluation for choledocholithiasis in
patients who have undergone cholecystectomy are lim-
ited. However, postcholecystectomy patients with normal
liver biochemical test results and normal US findings are
very unlikely to have choledocholithiasis.90
In postchole-
cystectomy patients referred for ERC because of suspected
choledocholithiasis after initial evaluation, the incidence
of choledocholithiasis is 33% to 43%.90,91
Both EUS91
and MRC90
have been shown to be highly accurate for de-
tecting choledocholithiasis in this patient subset, as well as
providing alternative diagnoses in many cases. As such,
ERC, EUS, and MRC may all be considered in the diagnos-
tic evaluation of postcholecystectomy patients when initial
The role of endoscopy in the evaluation of suspected choledocholithiasis
www.giejournal.org Volume 71, No. 1 : 2010 GASTROINTESTINAL ENDOSCOPY 5
laboratory and US data are abnormal yet nondiagnostic.
However, given that the ultimate incidence of choledo-
cholithiasis is still less than 50% in this population, EUS
and MRC may be preferable to ERC in this setting, partic-
ularly given their attenuated morbidity compared with
ERC.
The role of endoscopy for suspected
choledocholithiasis in patients with gallstone
pancreatitis
The approach to suspected choledocholithiasis in
patients with ABP may differ from patients with symptom-
atic cholelithiasis alone. Clinical investigations have dem-
onstrated a correlation between the presence of
persistent CBD stones and the severity of ABP, particularly
when biliopancreatic obstruction is present.92-94
Identify-
ing patients most likely to benefit from early detection
and treatment of retained CBD stones in ABP has been
an area of controversy, however.
ERC: Three randomized, controlled trials found
a trend toward benefit in patients with suspected ABP
who were randomized to early ERC (within 24-72 hours
from presentation) with biliary sphincterotomy versus
conservative management.95-97
In these trials, the
subgroups with pancreatitis predicted to be severe (by
Ranson98
or Glasgow99
scoring) who underwent early
ERC had significant reductions in morbidity and mortality.
These studies included patients with clinical evidence of
biliary obstruction and cholangitis, and an alternative
interpretation of these data is that patients with persistent
biliopancreatic obstruction, rather than those with
predicted severe ABP, benefit from early endoscopic
assessment and intervention. Accordingly, a randomized,
controlled trial of early ERC versus conservative manage-
ment in ABP that excluded patients with a bilirubin level
greater than 5 mg/dL found no benefit in morbidity and
mortality in patients with predicted severe ABP who
underwent early ERC.100
A recent meta-analysis of early
ERC versus conservative care in patients with ABP that
excluded patients with cholangitis also found no benefit
in morbidity and mortality in patients with predicted
severe ABP who underwent early ERC.101
Two random-
ized, controlled trials that sought to select patients with
ABP with persistent biliary obstruction, but not cholangi-
tis, for early ERC versus conservative care were conflicting
in their outcomes, although trial protocols differed.102,103
In summary, in the absence of clear evidence of a retained
stone, there does not seem to be a role for early ERC in
the evaluation and management of patients with mild
ABP. Conversely, in patients with ABP and concomitant
cholangitis, early ERC is strongly recommended given
the observed benefits in morbidity and mortality. Data
are conflicting as to the benefit of early ERC in patients
with predicted severe ABP or in ABP with clinical evidence
of biliary obstruction when acute cholangitis is absent.
EUS: Acute pancreatitis may cause duodenal and
pancreatic edema that could theoretically hinder EUS
and impair sonographic visualization of small stones in
the distal CBD. However, in several studies of acute pan-
creatitis, EUS provided an assessment of the bile duct in
almost all patients while maintaining a high level of accu-
racy for CBD stones (97%-100%).9,10,104
Given the risks
and uncertain benefit associated with ERC in patients
with ABP and the modest prevalence of choledocholithia-
sis in ABP (18%-33%),8-11
investigators have also targeted
this scenario for EUS-directed triage to ERC.83,105
In 2 series of patients with acute pancreatitis of
suspected biliary etiology, all subjects underwent sequen-
tial EUS and ERC (conducted by separate, blinded exam-
iners). EUS had a sensitivity of 91% to 97% and accuracy
of 97% to 98% for choledocholithiasis detection, similar
to or better than the performance of ERC in these stud-
ies.9,10
In a trial that randomized 140 patients with acute
pancreatitis of suspected biliary etiology to EUS versus
ERC, the bile duct was successfully evaluated more fre-
quently with EUS, and EUS was associated with a trend to-
ward less morbidity.83
No patients with a negative biliary
EUS finding experienced the development of recurrent
symptoms in more than a 2-year median follow-up, and
EUS identified cholelithiasis in 6 of 48 patients initially
labeled idiopathic after unrevealing transabdominal US
and ERC. A Monte Carlo decision analysis recently com-
pared selective ERC (for severe ABP, with supportive
care for mild ABP) with the EUS-first and MRC-first
approaches.106
The EUS-first strategy was preferable for
severe ABP in this analysis, with reduced costs, fewer
ERCs, and fewer complications.
RECOMMENDATIONS
1. We recommend that the initial evaluation of suspected
choledocholithiasis should include serum liver bio-
chemical tests and a transabdominal US of the right
upper quadrant. 444B These tests should be
used to risk-stratify patients to guide further evaluation
and management.
2. We recommend that patients with symptomatic choleli-
thiasis who are surgical candidates and have a low
probability of choledocholithiasis proceed to cholecys-
tectomy without additional biliary evaluation (Fig. 1).
444B
3. We recommend that patients with an intermediate
probability of choledocholithiasis undergo further eval-
uation with preoperative EUS or MRC or an IOC
(Fig. 1). 444B In this group of patients, we suggest
that ERC be deferred unless EUS, MRC, and IOC are
unavailable, given the less favorable risk profile of
ERC. 444B
4. We recommend that patients with a high probability of
choledocholithiasis undergo an evaluation of the bile
The role of endoscopy in the evaluation of suspected choledocholithiasis
6 GASTROINTESTINAL ENDOSCOPY Volume 71, No. 1 : 2010 www.giejournal.org
duct with therapeutic capability, generally preoperative
ERC (Fig. 1). 444B When available, laparoscopic
bile duct exploration can serve as an alternative to ERC.
5. We suggest that EUS or MRC be considered in the diag-
nostic evaluation of postcholecystectomy patients sus-
pected of having choledocholithiasis when initial
laboratory and US data are abnormal yet nondiagnostic.
44BB
6. We recommend against early ERC in the evaluation and
management of patients with mild ABP in the absence
of clear evidence of a retained stone. 444B
7. We recommend early ERC in patients with acute biliary
pancreatitis and concomitant cholangitis, given the
observed benefits in morbidity and mortality. 4444
8. We suggest that patients with acute biliary pancreatitis
and clinical evidence of biliary obstruction be consid-
ered for early ERC. 44BB We cannot recommend
for or against early ERC in patients with predicted se-
vere acute biliary pancreatitis in the absence of overt
biliary obstruction or cholangitis, given the lack of con-
sensus in the available data. 44BB
9. As patients with acute biliary pancreatitis are at least at
intermediate risk for choledocholithiasis, we suggest
pre-operative EUS or IOC be considered for these
patients when cholangitis or biliary obstruction are
absent. 44BB
Abbreviations: ABP, acute biliary pancreatitis; CBD, common bile duct;
ERC, endoscopic retrograde cholangiography; IDUS, intraductal US;
IOC, intraoperative cholangiography; MRC, magnetic resonance
cholangiography.
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1. Guyatt GH, Oxman AD, Vist GE, et al; GRADE Working Group. GRADE.
an emerging consensus on rating quality of evidence and strength of
recommendations. BMJ 2008;336:924-6.
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Prepared by: ASGE STANDARDS OF PRACTICE COMMITTEE
John T. Maple
Tamir Ben-Menachem
Michelle A. Anderson
Vasundhara Appalaneni
Subhas Banerjee
Brooks D. Cash
Laurel Fisher
M. Edwyn Harrison
Robert D. Fanelli
Norio Fukami
Steven O. Ikenberry
Rajeev Jain
Khalid Khan
Mary Lee Krinsky
Laura Strohmeyer
Jason A. Dominitz (Chair)
This document is a product of the Standards of Practice Committee. This
document was reviewed and approved by the Governing Board of the
American Society for Gastrointestinal Endoscopy. This document was
reviewed and endorsed by the Society of American Gastrointestinal and
Endoscopic Surgeons (SAGES) Guidelines Committee and by the SAGES
Board of Governors.
The role of endoscopy in the evaluation of suspected choledocholithiasis
www.giejournal.org Volume 71, No. 1 : 2010 GASTROINTESTINAL ENDOSCOPY 9

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Role of endoscopy in choledocholithiasis

  • 1. GUIDELINE The role of endoscopy in the evaluation of suspected choledocholithiasis This is one of a series of statements discussing the use of GI endoscopy in common clinical situations. The Stan- dards of Practice Committee of the American Society for Gastrointestinal Endoscopy prepared this text. In prepar- ing this guideline, a search of the medical literature was performed by using PubMed. Additional references were obtained from the bibliographies of the identified articles and from recommendations of expert consultants. When few or no data exist from well-designed prospective trials, emphasis is given to results of large series and reports from recognized experts. Guidelines for appropriate use of endoscopy are based on a critical review of the available data and expert consensus at the time that the guidelines are drafted. Further controlled clinical studies may be needed to clarify aspects of this guideline. This guideline may be revised as necessary to account for changes in technology, new data, or other aspects of clin- ical practice. The recommendations were based on reviewed studies and were graded on the strength of the supporting evidence (Table 1).1 This guideline is intended to be an educational device to provide information that may assist endoscopists in providing care to patients. This guideline is not a rule and should not be construed as establishing a legal stan- dard of care or as encouraging, advocating, requiring, or discouraging any particular treatment. Clinical deci- sions in any particular case involve a complex analysis of the patient’s condition and available courses of action. Therefore, clinical considerations may lead an endoscopist to take a course of action that varies from these guidelines. Gallstone disease affects more than 20 million Ameri- can adults2 at an annual cost of $6.2 billion.3 A subset of these patients will also have choledocholithiasis, including 5% to 10% of those undergoing laparoscopic cholecystec- tomy for symptomatic cholelithiasis4-7 and 18% to 33% of patients with acute biliary pancreatitis.8-11 The approach to patients with suspected choledocholithiasis requires careful consideration because missed common bile duct (CBD) stones pose a risk of recurrent symptoms, pancre- atitis, and cholangitis. However, the morbidity and cost from indiscriminant and/or invasive biliary evaluation should also be minimized. This guideline addresses the role of endoscopy in patients with suspected choledocholithiasis. INITIAL EVALUATION Choledocholithiasis is most commonly suspected in the scenarios of symptomatic cholelithiasis and acute biliary pancreatitis (ABP), with other presentations such as de novo bile duct stones in the postcholecystectomy patient occurring less often. The initial evaluation of suspected choledocholithiasis should include serum liver biochemi- cal tests (eg, alanine aminotransferase, aspartate amino- transferase, alkaline phosphatase, and total bilirubin) and a transabdominal ultrasound (US) of the right upper quadrant. Fractionation of bilirubin can be considered in clinical scenarios in which isolated indirect hyperbilirubi- nemia (eg, Gilbert syndrome) may be present. Liver biochemical tests may have the most utility in excluding the presence of CBD stones; the negative pre- dictive value of completely normal liver biochemical test results in a series of more than 1000 patients undergoing laparoscopic cholecystectomy was more than 97%, whereas the positive predictive value of any abnormal liver biochemical test result was only 15%.12 Although other series have reported modestly better positive predictive values for CBD stones for abnormal bilirubin, alkaline phosphatase, or g-glutamyl transpeptidase, these still gen- erally range from 25% to 50%.12-15 These latter cholestatic liver biochemical tests generally progressively increase with the duration and severity of biliary obstruction. As such, more abnormally elevated values will result in an increased likelihood of CBD stones.13,14 For example, in one study, a bilirubin level of 1.7 mg/dL or higher por- tended a specificity of 60% for choledocholithiasis, whereas the specificity increased to approximately 75% at a cutoff of 4 mg/dL.13 However, the mean bilirubin level in series of patients with choledocholithiasis has been re- ported at 1.5 to 1.9 mg/dL,14,15 and only a minority (one third or less) of patients with choledocholithiasis will have a bilirubin level of 4 mg/dL or higher.13,14 Transabdominal US has a relatively poor sensitivity (22%- 55%) for detecting CBD stones.16-19 However, US more reliably detects dilation of the CBD (sensitivity 77%-87%), a finding often associated with choledocholithiasis.20-23 Copyright ª 2010 by the American Society for Gastrointestinal Endoscopy 0016-5107/$36.00 doi:10.1016/j.gie.2009.09.041 www.giejournal.org Volume 71, No. 1 : 2010 GASTROINTESTINAL ENDOSCOPY 1
  • 2. The normal bile duct diameter is 3 to 6 mm,24-26 and mild dilation related to advancing age has been reported.26 Bili- ary dilation greater than 8 mm in a patient with an intact gallbladder is usually indicative of biliary obstruction.21 Also, the sonographic characterization of gallbladder stones harbors some predictive value for choledocholithiasis, with multiple small (!5 mm) stones posing a 4-fold higher risk of migration into the duct as opposed to larger and/or sol- itary stones.27 Given the relatively low prevalence (5%-10%) of choledocholithiasis in patients with symptomatic chole- lithiasis, a normal bile duct US has a 95% to 96% negative predictive value.12,28 Thus, although no single variable consistently strongly predicts choledocholithiasis in patients with symptomatic cholelithiasis, many investigators have noted that the probability of a CBD stone is higher in the presence of multiple abnormal prognostic signs.13,29,30 As a result, a number of different prognostic scores, formulas, and algorithms have been devised to help predict the probabil- ity of choledocholithiasis.13,14,29,31,32 Although there is no single accepted scoring system, by using factors such as age, liver test results, and US findings, patients can gener- ally be categorized into low (!10%), intermediate (10%- 50%), and high (O50%) probability of choledocholithiasis (Table 2). A CBD stone seen on US is the most reliable predictor of choledocholithiasis at subsequent endoscopic retrograde cholangiography (ERC) or surgery.13,31 The specificity of US for CBD stones is very high, with occa- sional discrepancies attributed to interval stone migration or falsely positive US findings. Otherwise, the most predic- tive variables seem to be cholangitis, a bilirubin level higher than 1.7 mg/dL, and a dilated CBD on US. The pres- ence of 2 or more of these variables results in a high prob- ability of a CBD stone.13,31 Advanced age (older than 55 years), elevation of a liver biochemical test result other than bilirubin, and pancreatitis are less robust predictors for choledocholithiasis.13,31 Conversely, nonjaundiced patients with a normal bile duct on US have a low proba- bility (!5%) of choledocholithiasis.12,28 A RISK-STRATIFIED DIAGNOSTIC APPROACH TO PATIENTS WITH SYMPTOMATIC CHOLELITHIASIS A proposed strategy to assign risk of choledocholithia- sis based on clinical predictors evident after initial diag- nostic evaluation is presented in Table 2. This table summarizes the relative importance of common clinical predictors for choledocholithiasis based on the available TABLE 1. GRADE system for rating the quality of evidence for guidelines Quality of evidence Definition Symbol High quality Further research is very unlikely to change our confidence in the estimate of effect. 4444 Moderate quality Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. 444B Low quality Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. 44BB Very low quality Any estimate of effect is very uncertain. 44BB Weaker recommendations are indicated by phrases such as ‘‘we suggest,’’ whereas stronger recommendations are typically stated as ‘‘we recommend.’’ Adapted from Guyatt et al.1 TABLE 2. A proposed strategy to assign risk of choledocholithiasis in patients with symptomatic cholelithiasis based on clinical predictors Predictors of choledocholithiasis13,14,29,31,32 Very strong CBD stone on transabdominal US Clinical ascending cholangitis Bilirubin O4 mg/dL Strong Dilated CBD on US (O6 mm with gallbladder in situ) Bilirubin level 1.8-4 mg/dL Moderate Abnormal liver biochemical test other than bilirubin Age older than 55 y Clinical gallstone pancreatitis Assigning a likelihood of choledocholithiasis based on clinical predictors12-14,28,29,31,32 Presence of any very strong predictor High Presence of both strong predictors High No predictors present Low All other patients Intermediate CBD, Common bile duct. The role of endoscopy in the evaluation of suspected choledocholithiasis 2 GASTROINTESTINAL ENDOSCOPY Volume 71, No. 1 : 2010 www.giejournal.org
  • 3. literature; however, it is not a validated clinical decision aid. A suggested management algorithm for patients with symptomatic cholelithiasis, based on whether they are at low, intermediate, or high probability of choledo- cholithiasis, is presented in Figure 1. Low risk of choledocholithiasis Patients with symptomatic cholelithiasis who are candi- dates for surgery and have a low probability of choledo- cholithiasis (!10%) should undergo cholecystectomy; no further evaluation is recommended because the cost and risks of additional preoperative biliary evaluation are not justified by the low probability of a CBD stone.12,28 Whether routine intraoperative cholangiography (IOC) or laparoscopic US should be performed at laparoscopic cholecystectomy, for purposes of both defining the biliary anatomy and for screening for CBD stones, is an area of controversy in the surgical literature.33-36 Intermediate risk of choledocholithiasis Patients at intermediate probability of choledocholithia- sis (10%-50%) after initial evaluation benefit from addi- tional biliary imaging to further triage the need for ductal stone clearance.28,37,38 Failure to identify CBD stones can result in recurrent symptoms, cholangitis, and ABP.39,40 Options for evaluation of these patients include endoscopic ultrasound (EUS), magnetic resonance cholangiography (MRC), preoperative ERC, and IOC or laparoscopic US to facilitate either removal at surgery or postoperative ERC. High risk of choledocholithiasis Patients at high probability of CBD stones (O50%) require further evaluation of the bile duct; because of the frequent need for therapy, typically preoperative ERC or op- erative cholangiography are undertaken. In the era of open cholecystectomy, there was no advantage found for preop- erative ERC over operative cholangiography and common duct exploration in randomized, controlled trials.41 Figure 1. A suggested management algorithm for patients with symptomatic cholelithiasis based on the degree of probability for choledocholithiasis. Modified from Tse et al.32 The role of endoscopy in the evaluation of suspected choledocholithiasis www.giejournal.org Volume 71, No. 1 : 2010 GASTROINTESTINAL ENDOSCOPY 3
  • 4. However, open cholecystectomy is now infrequently performed given the attenuated morbidity and shorter hos- pital stays associated with laparoscopic cholecystectomy. Two randomized, controlled trials compared 2-stage man- agement (preoperative ERC followed by laparoscopic cho- lecystectomy) with an all-surgical approach of laparoscopic IOC and transcystic stone removal or laparoscopic choledo- chotomy for patients at high risk of choledocholithiasis.42,43 In these studies, there was no difference in morbidity, mor- tality, or primary ductal clearance rates (88%) between the 2 arms. Other potential options include intraoperative or postoperative ERC for patients with positive IOC findings; laparoscopic antegrade placement of a transpapillary stent to ensure biliary access at postoperative ERC may also be considered.44 A more robust discussion of operative versus endoscopic management of choledocholithiasis in patients undergoing cholecystectomy is beyond the scope of this guideline. However, CBD stone detection and subsequent management are inseparably linked, and many of the tech- niques used for biliary evaluation and CBD stone removal are considerably operator dependent. Thus, the best strat- egies for the evaluation and management of choledocholi- thiasis in patients with symptomatic cholelithiasis will be heavily predicated on local expertise and available technology. Nonendoscopic biliary imaging modalities CT: Conventional (nonhelical) CT has historically dem- onstrated better sensitivity for choledocholithiasis than transabdominal US when composite diagnostic criteria are used (eg, the inclusion of indirect signs such as ductal dilation), although direct visualization of stones has not exceeded 75%.45 Helical CT has shown improved perfor- mance over conventional CT for choledocholithiasis, with 65% to 88% sensitivity and 73% to 97% specificity.46-49 Expense and radiation exposure have limited the use of CT as a first-line diagnostic test for choledocholithiasis, but in many instances, abdominal CT scans are ordered in the emergency department setting to evaluate and exclude competing potential diagnoses that may have sim- ilar presentations. MRC: MRC has 85% to 92% sensitivity and 93% to 97% specificity for choledocholithiasis detection, as assessed in 2 recent systematic reviews.50,51 However, the sensitivity of MRC seems to diminish in the setting of small (!6 mm) stones and has been reported as 33% to 71% in this clinical subset.52-54 CT cholangiography: CT cholangiography is per- formed by using helical CT in conjunction with a dedicated cholegraphic iodinated contrast agent that is taken up by the liver and excreted into the bile. Although its perfor- mance characteristics for choledocholithiasis detection are similar to those of MRC,46,55,56 concerns regarding the toxicity of available cholegraphic agents and significant radiation dose have limited the clinical adoption of this imaging modality. IOC: Intraoperative fluorocholangiography may be performed by insertion of small catheter into a cystic ductotomy or via the gallbladder (cholecystocholangiogra- phy) and injection of iodinated contrast dye with real-time fluoroscopic interpretation by the surgeon. IOC can be successfully completed in 88% to 100% of patients, has a reported sensitivity of 59% to 100% and specificity of 93% to 100% for choledocholithiasis, and typically requires between 10 and 17 minutes to complete during a laparo- scopic cholecystectomy.57 Laparoscopic US: Laparoscopic US transducers are available in a variety of viewing arrays, may be rigid or flex- ible, and fit through a conventional laparoscopic trocar. Laparoscopic US of the extrahepatic bile duct can be suc- cessfully completed in 88% to 100% of patients and can be performed in 4 to 10 minutes, with a reported sensitivity of 71% to 100% and specificity of 96% to 100%.57 Laparo- scopic US has a reportedly longer learning curve than does IOC. Endoscopic biliary imaging modalities EUS: EUS combines endoscopic visualization with 2-dimensional US and is well suited for biliary imaging given the close proximity of the extrahepatic bile duct to the proximal duodenum. Radial array echoendoscopes more frequently allow elongated views of the bile duct and are thus preferred by many endosonographers; however, the performance of linear array instruments for choledocholithiasis is also excellent, with series reporting a sensitivity of 93% to 97%.58,59 Two meta-analyses, each composed of more than 25 trials and more than 2500 pa- tients, reported an 89% to 94% sensitivity and 94% to 95% specificity of EUS for detecting choledocholithiasis, with ERC, IOC, or surgical exploration used as criterion stan- dards.60,61 EUS remains highly sensitive for stones smaller than 5 mm, and its performance does not seem adversely affected by decreasing stone size.62-64 Excluding examina- tions for esophageal cancer staging, complications with diagnostic EUS are rare (0.1%-0.3%).65-67 ERC: Because the risk of adverse events is higher with ERC than with noninvasive biliary imaging studies or EUS, the use of ERC as a diagnostic modality is best suited for those patients at high risk of choledocholithiasis because they are most likely to benefit from the therapeutic capa- bility of ERC. ERC has traditionally served as a criterion standard for choledocholithiasis detection; thus, data re- garding its operating characteristics are limited. However, the sensitivity of ERC with cholangiography alone has been reported as 89% to 93% with a specificity of 100% in studies that used subsequent biliary sphincterotomy and duct sweeping with balloons/baskets as the criterion standard.68,69 False-negative ERC findings for choledocho- lithiasis typically occur in the setting of small stones in a dilated duct. The risks of ERC include pancreatitis (1.3%-6.7%), infection (0.6%-5.0%), hemorrhage (0.3%-2.0%), and The role of endoscopy in the evaluation of suspected choledocholithiasis 4 GASTROINTESTINAL ENDOSCOPY Volume 71, No. 1 : 2010 www.giejournal.org
  • 5. perforation (0.1%-1.1%) in prospective series of unse- lected patients.70-76 However, several patient variables (eg, young age, female sex) have been identified that serve as risk factors for pancreatitis; similarly, coagulopathy increases bleeding risk and immunosuppression increases the risk of infection at ERC.72 Thus, risk estimates must be individualized to the patient. ERC-associated technologies: Small-caliber, high- frequency (12-30 MHz) wire-guided intraductal US (IDUS) probes can be passed through the instrument channel of a duodenoscope and into the bile duct without a previous sphincterotomy in nearly 100% of cases.69,77 IDUS has demonstrated excellent sensitivity (97%-100%) for choledocholithiasis,69,77 and some studies have shown modestly improved accuracy of ERC with IDUS for stone detection compared with cholangiography alone.77 How- ever, the clinical impact of the high sensitivity of IDUS for choledocholithiasis is uncertain because stones missed by ERC that are detected by IDUS tend to be small (!4 mm) and of unclear significance.69 Conventional ‘‘mother-daughter’’ or newer single-oper- ator cholangioscopy systems are most often used in the diagnosis of indeterminate biliary strictures and as an adjunct in the management of complicated stone disease, but may have a role in biliary stone detection in limited settings. Adherent or impacted stones may be difficult to differentiate from complex strictures or biliary polyps, and direct visualization has been valuable in characterizing these indeterminate filling defects.78 Others have re- ported a potential role for cholangioscopy in confirming ductal clearance in patients after stone extraction.79,80 Although they are potentially useful in specific clinical set- tings, given the additional time and expense incurred by IDUS and cholangioscopy, their overall role in the diagno- sis of choledocholithiasis remains limited. EUS-directed ERC Given the higher morbidity of ERC compared with EUS, several investigators recently evaluated sequential EUS and ERC in patients with suspected choledocholithiasis in an effort to better triage patients in need of treat- ment.81-84 These 4 trials randomized patients at intermedi- ate to high risk for choledocholithiasis to an EUS-first strategy versus an ERC-first strategy. Patients found to have CBD stones at EUS underwent subsequent therapeu- tic ERC, which was performed in the same setting in 3 of the 4 trials.81,83,84 Across the trials, 27% to 40% of patients randomized to EUS were found to have CBD stones, and the negative predictive value of EUS seemed to be robust, with only 0% to 4% of patients with normal EUS findings returning with pancreaticobiliary symptoms in 1 to 2 years of follow-up. Thus, this sequential approach in these stud- ies eliminated the need for 60% to 73% of ERC and its attendant risk. There was either less morbidity or a trend toward less morbidity associated with the EUS-first strat- egy across all studies. An EUS-guided diagnostic strategy also seems to be cost-effective for many patients with suspected choledo- cholithiasis. In a cost analysis associated with a prospective trial of EUS for suspected choledocholithiasis in more than 450 patients, an EUS-first strategy was cost-effective for patients with an estimated likelihood of CBD stones of less than 61%, with the ERC-first strategy proving the dominant strategy for patients at higher risk.85 Similarly, a decision analysis assessing the roles of IOC, ERC, and EUS in patients undergoing laparoscopic cholecystectomy found EUS to be cost-effective when the estimated risk of CBD stones was 11% to 55%.37 In both of these cost anal- yses, EUS and subsequent therapeutic ERC were per- formed on separate days; procedures performed in tandem with a single sedation may yield even greater savings. The role of endoscopy for suspected choledocholithiasis in the postcholecystectomy patient Choledocholithiasis after cholecystectomy may result from either a migrated gallbladder stone not detected in the perioperative period or a stone forming de novo in the common bile duct. Diagnostic considerations are slightly different in these patients than in those with a gall- bladder in situ. Although patients presenting with pain, abnormal liver biochemical tests, jaundice, or fever may have choledocholithiasis, alternative processes such as bile leak, iatrogenic biliary stricture, and biliary-type sphincter of Oddi dysfunction are additional possibilities in the postcholecystectomy patient. Generally, the initial evaluation of these patients should include serum liver biochemical tests and a transabdominal US, mirroring the approach to the precholecystectomy patient with symptomatic cholelithiasis. However, dilation of the common bile duct after cholecystectomy has been reported,86,87 so using a 6-mm cutoff for normal is likely not appropriate for this population. Also, some patients reporting postcholecystectomy pain may have chronic abdominal pain unrelated to their biliary tree, and thus unresolved by cholecystectomy. In these patients, use of narcotic analgesics is not uncommon, and biliary dilation related to narcotic use has also been reported.88,89 Data regarding the evaluation for choledocholithiasis in patients who have undergone cholecystectomy are lim- ited. However, postcholecystectomy patients with normal liver biochemical test results and normal US findings are very unlikely to have choledocholithiasis.90 In postchole- cystectomy patients referred for ERC because of suspected choledocholithiasis after initial evaluation, the incidence of choledocholithiasis is 33% to 43%.90,91 Both EUS91 and MRC90 have been shown to be highly accurate for de- tecting choledocholithiasis in this patient subset, as well as providing alternative diagnoses in many cases. As such, ERC, EUS, and MRC may all be considered in the diagnos- tic evaluation of postcholecystectomy patients when initial The role of endoscopy in the evaluation of suspected choledocholithiasis www.giejournal.org Volume 71, No. 1 : 2010 GASTROINTESTINAL ENDOSCOPY 5
  • 6. laboratory and US data are abnormal yet nondiagnostic. However, given that the ultimate incidence of choledo- cholithiasis is still less than 50% in this population, EUS and MRC may be preferable to ERC in this setting, partic- ularly given their attenuated morbidity compared with ERC. The role of endoscopy for suspected choledocholithiasis in patients with gallstone pancreatitis The approach to suspected choledocholithiasis in patients with ABP may differ from patients with symptom- atic cholelithiasis alone. Clinical investigations have dem- onstrated a correlation between the presence of persistent CBD stones and the severity of ABP, particularly when biliopancreatic obstruction is present.92-94 Identify- ing patients most likely to benefit from early detection and treatment of retained CBD stones in ABP has been an area of controversy, however. ERC: Three randomized, controlled trials found a trend toward benefit in patients with suspected ABP who were randomized to early ERC (within 24-72 hours from presentation) with biliary sphincterotomy versus conservative management.95-97 In these trials, the subgroups with pancreatitis predicted to be severe (by Ranson98 or Glasgow99 scoring) who underwent early ERC had significant reductions in morbidity and mortality. These studies included patients with clinical evidence of biliary obstruction and cholangitis, and an alternative interpretation of these data is that patients with persistent biliopancreatic obstruction, rather than those with predicted severe ABP, benefit from early endoscopic assessment and intervention. Accordingly, a randomized, controlled trial of early ERC versus conservative manage- ment in ABP that excluded patients with a bilirubin level greater than 5 mg/dL found no benefit in morbidity and mortality in patients with predicted severe ABP who underwent early ERC.100 A recent meta-analysis of early ERC versus conservative care in patients with ABP that excluded patients with cholangitis also found no benefit in morbidity and mortality in patients with predicted severe ABP who underwent early ERC.101 Two random- ized, controlled trials that sought to select patients with ABP with persistent biliary obstruction, but not cholangi- tis, for early ERC versus conservative care were conflicting in their outcomes, although trial protocols differed.102,103 In summary, in the absence of clear evidence of a retained stone, there does not seem to be a role for early ERC in the evaluation and management of patients with mild ABP. Conversely, in patients with ABP and concomitant cholangitis, early ERC is strongly recommended given the observed benefits in morbidity and mortality. Data are conflicting as to the benefit of early ERC in patients with predicted severe ABP or in ABP with clinical evidence of biliary obstruction when acute cholangitis is absent. EUS: Acute pancreatitis may cause duodenal and pancreatic edema that could theoretically hinder EUS and impair sonographic visualization of small stones in the distal CBD. However, in several studies of acute pan- creatitis, EUS provided an assessment of the bile duct in almost all patients while maintaining a high level of accu- racy for CBD stones (97%-100%).9,10,104 Given the risks and uncertain benefit associated with ERC in patients with ABP and the modest prevalence of choledocholithia- sis in ABP (18%-33%),8-11 investigators have also targeted this scenario for EUS-directed triage to ERC.83,105 In 2 series of patients with acute pancreatitis of suspected biliary etiology, all subjects underwent sequen- tial EUS and ERC (conducted by separate, blinded exam- iners). EUS had a sensitivity of 91% to 97% and accuracy of 97% to 98% for choledocholithiasis detection, similar to or better than the performance of ERC in these stud- ies.9,10 In a trial that randomized 140 patients with acute pancreatitis of suspected biliary etiology to EUS versus ERC, the bile duct was successfully evaluated more fre- quently with EUS, and EUS was associated with a trend to- ward less morbidity.83 No patients with a negative biliary EUS finding experienced the development of recurrent symptoms in more than a 2-year median follow-up, and EUS identified cholelithiasis in 6 of 48 patients initially labeled idiopathic after unrevealing transabdominal US and ERC. A Monte Carlo decision analysis recently com- pared selective ERC (for severe ABP, with supportive care for mild ABP) with the EUS-first and MRC-first approaches.106 The EUS-first strategy was preferable for severe ABP in this analysis, with reduced costs, fewer ERCs, and fewer complications. RECOMMENDATIONS 1. We recommend that the initial evaluation of suspected choledocholithiasis should include serum liver bio- chemical tests and a transabdominal US of the right upper quadrant. 444B These tests should be used to risk-stratify patients to guide further evaluation and management. 2. We recommend that patients with symptomatic choleli- thiasis who are surgical candidates and have a low probability of choledocholithiasis proceed to cholecys- tectomy without additional biliary evaluation (Fig. 1). 444B 3. We recommend that patients with an intermediate probability of choledocholithiasis undergo further eval- uation with preoperative EUS or MRC or an IOC (Fig. 1). 444B In this group of patients, we suggest that ERC be deferred unless EUS, MRC, and IOC are unavailable, given the less favorable risk profile of ERC. 444B 4. We recommend that patients with a high probability of choledocholithiasis undergo an evaluation of the bile The role of endoscopy in the evaluation of suspected choledocholithiasis 6 GASTROINTESTINAL ENDOSCOPY Volume 71, No. 1 : 2010 www.giejournal.org
  • 7. duct with therapeutic capability, generally preoperative ERC (Fig. 1). 444B When available, laparoscopic bile duct exploration can serve as an alternative to ERC. 5. We suggest that EUS or MRC be considered in the diag- nostic evaluation of postcholecystectomy patients sus- pected of having choledocholithiasis when initial laboratory and US data are abnormal yet nondiagnostic. 44BB 6. We recommend against early ERC in the evaluation and management of patients with mild ABP in the absence of clear evidence of a retained stone. 444B 7. We recommend early ERC in patients with acute biliary pancreatitis and concomitant cholangitis, given the observed benefits in morbidity and mortality. 4444 8. We suggest that patients with acute biliary pancreatitis and clinical evidence of biliary obstruction be consid- ered for early ERC. 44BB We cannot recommend for or against early ERC in patients with predicted se- vere acute biliary pancreatitis in the absence of overt biliary obstruction or cholangitis, given the lack of con- sensus in the available data. 44BB 9. As patients with acute biliary pancreatitis are at least at intermediate risk for choledocholithiasis, we suggest pre-operative EUS or IOC be considered for these patients when cholangitis or biliary obstruction are absent. 44BB Abbreviations: ABP, acute biliary pancreatitis; CBD, common bile duct; ERC, endoscopic retrograde cholangiography; IDUS, intraductal US; IOC, intraoperative cholangiography; MRC, magnetic resonance cholangiography. REFERENCES 1. Guyatt GH, Oxman AD, Vist GE, et al; GRADE Working Group. GRADE. an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008;336:924-6. 2. 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Acute biliary pancreatitis: the roles of endo- scopic ultrasonography and endoscopic retrograde cholangiopan- creatography. Surgery 1998;124:14-21. 105. Prat F, Edery J, Meduri B, et al. Early EUS of the bile duct before endoscopic sphincterotomy for acute biliary pancreatitis. Gastroint- est Endosc 2001;54:724-9. 106. Romagnuolo J, Currie G. Calgary Advanced Therapeutic Endoscopy Center (ATEC) study group. Noninvasive vs. selective invasive biliary imaging for acute biliary pancreatitis: an economic evaluation by using decision tree analysis. Gastrointest Endosc 2005;61:86-97. Prepared by: ASGE STANDARDS OF PRACTICE COMMITTEE John T. Maple Tamir Ben-Menachem Michelle A. Anderson Vasundhara Appalaneni Subhas Banerjee Brooks D. Cash Laurel Fisher M. Edwyn Harrison Robert D. Fanelli Norio Fukami Steven O. Ikenberry Rajeev Jain Khalid Khan Mary Lee Krinsky Laura Strohmeyer Jason A. Dominitz (Chair) This document is a product of the Standards of Practice Committee. This document was reviewed and approved by the Governing Board of the American Society for Gastrointestinal Endoscopy. This document was reviewed and endorsed by the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Guidelines Committee and by the SAGES Board of Governors. The role of endoscopy in the evaluation of suspected choledocholithiasis www.giejournal.org Volume 71, No. 1 : 2010 GASTROINTESTINAL ENDOSCOPY 9