ORIGINAL ARTICLE

Preoperative predictors of choledocholithiasis in patients

presenting with acute calculous cholecystitis
Phillip R. Chisholm, MD,1 Arpan H. Patel, MD,1 Ryan J. Law, DO,1 Allison R. Schulman, MD, MPH,1
Arti O. Bedi, MD,1 Richard S. Kwon, MD, MS,1 Erik J. Wamsteker, MD,1 Michelle A. Anderson, MD, MS,1
Grace H. Elta, MD,1 Shail M. Govani, MD, MSc,1,3,4,* Anoop Prabhu, MD1,2,*
Ann Arbor, Michigan; San Antonio, Texas, USA

Background and Aims: Markedly increased liver chemistries in patients presenting with acute calculous chole-
cystitis (AC) often prompt an evaluation for concomitant choledocholithiasis (CDL). However, current guidelines
directing the workup for CDL fail to address this unique population. The aims of this study are to define the range
of presenting laboratory values and imaging findings in AC, develop a model to predict the presence of concur-
rent CDL, and develop a management algorithm that can be easily applied on presentation.
Methods: We conducted a retrospective review of patients presenting with AC to a large tertiary hospital over a
3.5-year period. CDL was defined as common bile duct (CBD) stone(s), sludge, or debris seen on any of the
following studies: US, CT, magnetic resonance imaging/MRCP, EUS, ERCP, or intraoperative cholangiogram. A
multivariable model to predict CDL was developed on 70% of the patients and validated on the remaining 30%.
Results: A total of 366 patients were identified and 65 (17.8%) had concurrent CDL. Univariable analysis was used
to predict CDL and demonstrated statistically significant odds ratios for transaminases >3 times the upper limit of
normal, alkaline phosphatase (AlkPhos) above normal, lipase >3 times the upper limit of normal, total
bilirubin 1.8 mg/dL, and CBD diameter >6 mm. In the validation cohort, an optimal model containing alanine
transaminase (ALT) >3 times the upper limit of normal, abnormal AlkPhos, and CBD diameter >6 mm was found
to have an area under the receiver operating curve of 0.91. When 0 or 1 risk factors were present, 98.6% of
patients did not have CDL. When all 3 risk factors were present, 77.8% were found to have CDL.
Conclusions: The prevalence of CDL is high among patients with AC. When a validated model is used, applica-
tion of cutoffs for ALT, AlkPhos, and CBD diameter can effectively triage patients with low and high likelihood for
CDL to surgery or ERCP, respectively. (Gastrointest Endosc 2018;-:1-7.)

INTRODUCTION serum transaminases, alkaline phosphatase (AlkPhos),

The diagnosis of acute calculous cholecystitis (AC)
involves a combination of clinical, laboratory, and imaging
findings.1,2 The initial laboratory evaluation of patients with
suspected cholecystitis often reveals modest increases in
and total bilirubin. In situations where these indices are
significantly increased, concern for concomitant choledo-
cholithiasis (CDL) is often raised. Depending on the
clinical suspicion for CDL, the preoperative evaluation
traditionally involves one or more of the following

Abbreviations: AC, acute calculous cholecystitis; AlkPhos, alkaline phos- 0016-5107/$36.00

phatase; ALT, alanine transaminase; ASGE, American Society for Gastro-
intestinal Endoscopy; AST, aspartate transaminase; AUROC, area under
the receiver operating curve; CBD, common bile duct; CDL, choledocho-
lithiasis; CI, confidence interval; IOC, intraoperative cholangiogram;
MRI, magnetic resonance imaging; OR, odds ratio.
DISCLOSURE: All authors disclosed no financial relationships relevant
to this publication.
*Drs Govani and Prabhu contributed equally to this article.
Copyright ª 2018 by the American Society for Gastrointestinal Endoscopy
https://doi.org/10.1016/j.gie.2018.11.017
Received August 25, 2018. Accepted November 7, 2018.
Current affiliations: University of Michigan Health Care System, Ann Arbor,
Michigan (1); VA Healthcare System, Ann Arbor, Michigan (2); South Texas
VA Healthcare System, San Antonio, Texas (3); UT Health San Antonio, San
Antonio, Texas, USA (4).
Reprint requests: Phillip R. Chisholm, MD, Medical College of Wisconsin,
HUB for Collaborative Medicine, 8701 Watertown Plank Road,
Milwaukee, WI 53226.

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Preoperative predictors of choledocholithiasis
investigations: EUS, MRCP, intraoperative cholangiogram
(IOC), or ERCP.3–9 These tests can be expensive, invasive,
associated with significant adverse events, and often delay
definitive care.10–13
Much of the motivation for this approach comes from
American Society for Gastrointestinal Endoscopy (ASGE)
guidelines directed at identifying patients who are at
high risk for CDL.4 However, these guidelines are
derived largely from studies of individuals without
cholecystitis, and thus likely represent a distinct and
separate patient population from those with concomitant
AC. In addition, these guidelines have been limited by
poor performance on retrospective validation studies and
may result in unnecessarily high referral rates for
diagnostic ERCP.14,15 Other studies to address this ques-
tion in patients with AC have had similar limitations.16–21
It remains unclear if unique factors predict the presence
of bile duct stones in this specific subset of patients and
when further testing should be performed for
intermediate-risk patients.20 We set out to both identify
the distribution of presenting laboratory and imaging
features and create a model to appropriately direct
patients who would benefit from preoperative endoscopic
intervention or imaging before cholecystectomy.
MATERIALS AND METHODS
We performed a retrospective review of all patients pre-
senting between January 1, 2013, and June 30, 2016, with a
preoperative clinical diagnosis of AC who underwent a cho-
lecystectomy on the same admission to the University of
Michigan Medical Center, a large tertiary academic medical
center. The study was approved by the University of Mich-
igan Institutional Review Board (study ID, HUM00115511).
To identify patients, we queried our electronic medical
record database for ICD-9 and ICD-10 codes associated
with acute cholecystitis (Supplementary Table 1, available
online at www.giejournal.org). The extracted records
were manually reviewed (P.R.C., A.H.P.). Patients were
excluded if the ICD coding did not match the
preoperative clinical diagnosis as determined by the
surgeon performing the cholecystectomy. Patients were
also excluded if preoperative liver function test or
imaging results (US, CT, or magnetic resonance imaging
[MRI]) were not available for review in the electronic
medical record.
Demographic data included age at the time of the pro-
cedure, sex, height, weight, medications, and comorbid-
ities. Imaging data included reports from abdominal US,
CT, IOC, MRI, MRCP, EUS, and ERCP. Surgical operative
notes were reviewed and approach, operative findings,
and any intraoperative adverse events were noted. Labora-
tory data between the time of presentation and surgical
intervention were collected. As cholecystitis is primarily
a clinical diagnosis, postoperative pathology was not
2 GASTROINTESTINAL ENDOSCOPY Volume -, No. - : 2019
Chisholm et al
considered in confirming or refuting the diagnosis of acute
cholecystitis.
Patients were identified as having CDL if a common
bile duct (CBD) stone was detected on any of the above
imaging studies, including those found intraoperatively
at IOC. For the purposes of this study, we considered
CBD sludge or debris seen on any imaging study as
CDL. All other patients were placed in a group labeled
“no CDL.”
Given that patients may present to medical attention at
many time points during their presentation of AC and
laboratory results may fluctuate in the disease course,
rather than using presenting values, we used the highest
recorded value before surgical intervention for our anal-
ysis, or “peak preoperative” value.
The relationship between CDL, preoperative labora-
tory results, and imaging results was then assessed using
descriptive statistics with SAS 9.4 (Cary, NC). A model
development cohort, consisting of a random 70% sample
of our study population, was selected for univariable anal-
ysis of the laboratory and imaging data. For our analysis,
we used serum transaminase and lipase values greater
than 3 times the upper limit of normal, and AlkPhos
values above the upper limit of normal for our reference
laboratory results. In addition, based on previous guide-
lines for CDL, we used a CBD diameter >6 mm, total
bilirubin 1.8 mg/dL, and total bilirubin >4 mg/dL as cut-
off values.4
Odds ratios (ORs) were calculated, and a threshold for
statistical significance was set at a P value <.05. We
selected laboratory and imaging predictors found to be sig-
nificant in univariable analysis from our model develop-
ment cohort for development of multivariable models
predicting the presence of CDL in a logistic regression
model. The area under the receiver operating curve
(AUROC) was calculated for each model. We used the
remaining 30% of patients not selected for our model
development as our validation cohort to test each pro-
posed model. The management algorithm proposed was
designed based on the model found to both maximize
the AUROC as well as the number of patients at either
high or low risk for CDL.
RESULTS
Patient population
A total of 737 patients were identified in our query of the
medical records and, of these individuals, 366 patients met
the inclusion criteria (Fig. 1). The most frequent reason for
exclusion was cholecystectomy done for reasons other than
AC (biliary colic, gallstone pancreatitis, acalculous
cholecystitis, ascending cholangitis). Table 1 shows the
general characteristics for the study population. The mean
age of the patients was 52.0 years and 40.4% were male.
Most of the surgeries (77.9%) were performed
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Chisholm et al Preoperative predictors of choledocholithiasis

Performance of ASGE guidelines

The performance of the current ASGE guidelines for
evaluation of suspected CDL was evaluated in our study
population.4 Under these guidelines, patients with any
very strong predictor (serum total bilirubin >4 mg/dL,
ascending cholangitis, CBD stone on transabdominal
US), and/or both strong predictors (total bilirubin 1.8-
1.4 mg/dL, CBD diameter >6 mm) are considered high
risk and direct referral for ERCP is recommended.
Patients considered low risk under these guidelines
(total serum bilirubin <1.8, CBD <6 mm, normal liver
biochemical tests, age <55 years, and no evidence of
gallstone pancreatitis) would be recommended for
direct referral for cholecystectomy. In our cohort, these
guidelines classified 59 patients as high risk, and only 34
Figure 1. Patient flow diagram. patients actually had CDL, leading to a negative ERCP
rate of 42.4%. Only 72 patients (19.7%) would be
categorized at low risk and, as a result, 229 (62.6%)
would be referred for further testing despite not
TABLE 1. General patient characteristics having CDL.
Characteristic

Male, n (%) 148 (40.4) Univariable and multivariable predictors for

Age (years), mean (SD) 52.0 (17.3) choledocholithiasis
Imaging studies used, n (%)
The demographic and laboratory characteristics for the
model development and validation cohorts can be found
US 353 (96.5)
in Supplementary Table 2, available online at www.
CT 90 (24.6) giejournal.org. There were no statistically significant
Cholecystography/HIDA 121 (33.1) differences between these cohorts. In the model
MRI/MRCP 26 (7.1) development cohort, laboratory and demographic
EUS 29 (7.9) variables were evaluated as potential univariable
IOC 38 (10.4) predictors for CDL (Table 3). The odds ratios for
Surgical approach, n (%)
predicting CDL in our model development cohort are
shown in Table 3. Statistically significant ORs for
Laparoscopic 285 (77.9)
predicting CDL were found to be AST >3 times the
Open 25 (6.8) upper limit of normal (OR, 19.97; 95% confidence
Converted to open 56 (15.3) interval [CI], 8.97-44.49), ALT >3 times the upper limit of
SD, Standard deviation; HIDA, hepatobiliary iminodiacetic acid scan; MRI, magnetic normal (OR, 23.58; 95% CI, 10.5-52.98), AlkPhos level
resonance imaging; IOC, intraoperative cholangiogram. above normal (OR, 9.26; 95% CI, 4.13-20.74), lipase level
>3 times the upper limit of normal (OR, 5.54; 95% CI,
laparoscopically. Of the patients included, 65 (17.8%) were 2.02-15.21), bilirubin 1.8 mg/dL (OR, 7.56; 95% CI, 3.86-
found to have concomitant CDL. 14.8), total bilirubin >4 mg/dL (OR, 7.97; 95% CI, 3.06-
20.81), and CBD diameter >6 mm (OR, 7.83; 95% CI,
3.87-15.84).
Preoperative laboratory values Using the 5 variables found to be most influential, we
The mean peak preoperative laboratory values are pre- developed 3 multivariable models based on the presence
sented in Table 2. Transaminases, AlkPhos, and total of cumulative risk factors. The performance characteristics
bilirubin levels were frequently increased for patients of each model on the model validation cohort are pre-
with AC. The CDL group had statistically significantly sented in Table 4. Each model performed well, with each
higher serum aspartate transaminase (AST), alanine AUROC 0.90. The optimal model (model 1) met our
transaminase (ALT), total bilirubin, and AlkPhos levels initial goals of maximizing AUROC while distinguishing
and had larger CBD diameter than patients with no CDL. the most high- and low-risk patients.
No statistically significant differences were detected In the validation cohort, application of this model
between the no CDL and CDL groups for lipase, to a management algorithm (Fig. 2) defined a
albumin, international normalized ratio, white blood cell management strategy for 78.3% of patients: 69.8% were
count, and platelet count. recommended for direct referral for cholecystectomy

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Preoperative predictors of choledocholithiasis Chisholm et al

TABLE 2. Comparison of select serum and imaging characteristics among patients with and without choledocholithiasis

Peak preoperative laboratory values (normal values) All (n [ 366), mean (SD) No CDL, mean (SD) CDL, mean (SD) P value

WBC (4-10  10 /mL) 3

12.8 (5.5) 12.8 (5.2) 12.6 (6.9) .89
Platelet count (150-400  103/mL) 256.9 (88.3) 255.1 (85.0) 265.6 (102.7) .45
INR (< 1.4) 1.2 (0.8) 1.2 (0.9) 1.2 (0.6) .75
Serum albumin (3.5-4.9 g/dL) 4.2 (0.5) 4.2 (0.5) 4.1 (0.5) .56
AST (8-30 IU/L) 139.7 (326.6) 103.4 (319.2) 307.6 (309.8) <.01
ALT (< 35 IU/L) 130.7 (214.1) 88.2 (174.5) 327.7 (266.3) <.01
AlkPhos (30-116 IU/L) 148.6 (135.5) 126.2 (87.8) 252.2 (235.2) <.01
Total bilirubin (0.2-1.2 mg/dL) 1.6 (1.9) 1.2 (1.4) 3.3 (2.7) <.01
Lipase (<150 mg/dL) 190.2 (783.8) 150.5 (730.1) 362.3 (971.6) .1
Bile duct diameter on US 5.1 (2.6) 4.6 (2.1) 7.3 (3.2) <.01
CDL, Choledocholithiasis; WBC, white blood cell count; INR, international normalized ratio; AST, serum aspartate transaminase; ALT, serum alanine transaminase; AlkPhos, serum
alkaline phosphatase.

TABLE 3. Univariable predictors for the presence of choledocholithiasis in the model development cohort

Cutoff Upper limit of normal OR 95% CI P value

Age NA 1 0.98-1.02 .72

Male sex (versus female) NA 1.18 0.64-2.20 .6
WBC >10  10 /mL 3
10  10 /mL 3
0.83 0.44-1.59 .58
Platelet count >400  103/mL 400  103/mL 0.54 0.12-2.45 .43
INR >1.4 1.4 0.97 0.27-3.53 .96
Albumin 4.9 g/dL 0.72 0.37-1.37 .31
AST >90 IU/L 30 IU/L 19.97 8.97-44.49 <.01
ALT >105 IU/L 35 IU/L 23.58 10.50-52.98 <.01
AlkPhos >116 IU/L 116 IU/L 9.26 4.13-20.74 <.01
Total bilirubin 1.8 mg/dL 1.2 mg/dL 7.56 3.86-14.80 <.01
Total bilirubin >4.0 mg/dL 1.2 mg/dL 7.97 3.06-20.81 <.01
Lipase >150 mg/dL 50 mg/dL 5.54 2.02-15.21 <.01
CBD diameter >6 mm - 7.83 3.87-15.84 <.01
OR, Odds ratio; CI, confidence interval; NA, not applicable; WBC, white blood cell count; INR, international normalized ratio; AST, serum aspartate transaminase; ALT, serum alanine
transaminase; AlkPhos, serum alkaline phosphatase; CBD, common bile duct.

without additional testing and 8.5% were recommended
for preoperative ERCP without MRCP or EUS beforehand.
The remaining patients (21.7%) would be referred for
confirmatory tests via MRCP or EUS before definitive
intervention.
DISCUSSION
The presence of significantly abnormal liver indices in pa-
tients presenting with AC poses a significant diagnostic and
therapeutic dilemma. Suspicion for concurrent CDL can delay
definitive cholecystectomy, sometimes inappropriately when
CDL is ultimately not identified. In addition, assessment of
CBD stones in the background of concomitant AC likely rep-
resents a subset of patients distinct from those addressed by
current management guidelines and thus requires a tailored
approach. In this study, we defined the range of presenting
laboratory and imaging findings in patients with AC and strat-
ified these values based on the presence or absence of CDL.
The risk factors identified by univariable modeling were
then successfully applied to achieve high-performing multi-
variable models.
As in other studies, we found that increases in levels of
transaminases, total bilirubin, and AlkPhos frequently
occur in AC, with or without the presence of CDL.
Studies of liver histology in acute cholecystitis have shown
multiple contributors to abnormal liver chemistries, most
commonly a non-specific reactive hepatitis.22 Additional
studies have shown that this hepatocellular injury is
acute and transient with return of liver enzyme levels to
normal after cholecystectomy.23,24 These studies highlight
the importance of developing other tools to differentiate
increased liver function test results with uncomplicated

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Chisholm et al Preoperative predictors of choledocholithiasis

TABLE 4. Performance characteristics of multivariable model based on presence of cumulative risk factor cutoffs in the validation cohort

Model development cohort Validation cohort

Cumulative
Predictor Sensitivity Specificity False False percentage at or
Model Predictors AUROC cutoff* (%) (%) positive (%) negative (%) below cutoff

1 AlkPhos > ULN, 0.90 (0.86-0.95) 0 15 (100.0) 53 (58.2) 38 (71.7) 0 (0.0) 50

ALT > 3 ULN, 1 14 (93.3) 73 (80.2) 18 (56.3) 1 (1.4) 69.8
CBD >6 mm
2 7 (46.7) 89 (97.8) 2 (22.2) 8 (8.3) 91.5
2 AlkPhos > ULN, 0.91 (0.87-0.95) 0 15 (100.0) 50 (55.0) 41 (73.2) 0 (0.0) 47.2
ALT > 3 ULN, 1 14 (93.3) 72 (79.1) 19 (57.6) 1 (1.4) 68.9
CBD >6 mm,
total bilirubin >1.8 3 4 (26.7) 89 (97.8) 2 (33.3) 11 (11.0) 94.3

3 AlkPhos > ULN, 0.92 (0.89-0.95) 0 15 (100.0) 47 (51.7) 44 (74.6) 0 (0.0) 44.3
ALT > 3 ULN, 1 15 (100.0) 68 (74.7) 23 (60.5) 0 (0.0) 64.2
AST > 3 ULN
CBD >6 mm, 2 13 (86.7) 76 (83.5) 15 (53.6) 2 (2.6) 73.6
total bilirubin >1.8 3 11 (73.3) 81 (89.0) 10 (47.6) 4 (4.7) 80.2
4 4 (26.7) 89 (97.8) 2 (33.3) 11 (11.0) 94.3
AUROC, Area under the receiver operating curve; AlkPhos, serum alkaline phosphatase; ULN, upper limit of normal; ALT, serum alanine transaminase; CBD, common bile duct; AST,
serum aspartate transaminase.
*Predictor cutoff represents the number of predictors at that point. For example, for the first model, a cutoff of 2 represents a model that predicts choledocholithiasis at 3
predictors versus 0, 1, or 2 predictors present.

acute cholecystitis versus those caused by other factors
such as CDL.
Our study found that nearly 18% of patients with AC
have concurrent CDL. This high rate of CDL corresponds
with other reports suggesting that CDL is more common
in patients undergoing cholecystectomy for AC as opposed
to those having cholecystectomy for other indications.25
This further illustrates that AC represents a population at
higher risk for CDL and may require an alternative CDL
risk stratification strategy other than those proposed by
current guidelines.
In the present study, univariable predictors of CDL
informed multivariable models based on cumulative risk
factors. As each model demonstrated similar performance,
we selected model 1 as the basis of our proposed manage-
ment algorithm (Fig. 2), because it contained the fewest
variables and thus was the most convenient for rapid
clinical application. This algorithm uses only 3 variables
(increased AlkPhos, ALT >3 times the upper limit of
normal, and CBD diameter >6 mm) and differentiates
patients into high, low, and intermediate risk of CDL.
We opted to use the peak preoperative laboratory
values in the statistical analysis to address the common
clinical dilemma of whether the proposed management
plan should change when there is a significant change in
serial serum liver chemistries before proposed interven-
tion. To evaluate the impact of using peak preoperative
values for this study, we examined the performance charac-
teristics of our selected multivariable model using the first
available presenting laboratory values (Supplementary
Table 3, available online at www.giejournal.org) and
found no significant reduction in model performance
(AUROC, 0.86; range, 0.81-0.92).
On the basis of these data, we propose a management
algorithm for patients with acute cholecystitis for whom
the presence of CDL is in question (Fig. 2). The goal of
our algorithm was to limit (1) the number of patients
referred directly for cholecystectomy with concurrent
CDL (false negative), and (2) the number of patients who
undergo unnecessary diagnostic ERCP when CDL is
ultimately not present (false positive). In previous
studies, CBD stones were found to complicate close to
5% of cholecystectomies for low-risk patients with symp-
tomatic cholelithiasis from any cause,26 suggesting a
model that misses less than 5% of cases with CDL is
appropriate.27 Similarly, although the significant risk
profile of ERCP demands it be used in the most
appropriate settings, false-negative ERCP will occur despite
thorough preprocedural evaluations. Indeed, there is
disagreement among experts and limited data regarding
an acceptable rate of false-negative ERCP. In an attempt
to clarify this, a recent survey of gastroenterologists deter-
mined that a negative ERCP rate of 25% was acceptable
given the potential benefit of the procedure.27 Thus, our
model selection and subsequent proposed algorithm was
derived with the guidance of these 2 thresholds.
In this algorithm, patients with 0 or 1 risk factor are
directed toward cholecystectomy, patients with 2 risk fac-
tors are recommended to have MRCP or EUS to first
exclude CDL, and patients with 3 risk factors should be
considered for direct referral for preoperative ERCP.
Applied to our validation cohort, patients with 0 to 1
CDL risk factor (approximately 70% of this cohort) would
be referred directly for cholecystectomy with only 1.4% un-
dergoing cholecystectomy in the presence of CBD stones.
Patients with all 3 risk factors (approximately 10% of the

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Preoperative predictors of choledocholithiasis
Figure 2. Management algorithm for patients presenting with acute calculous cholecystitis. ALT, Serum alanine transaminase.
validation cohort) had negative ERCP 22% of the time. Us-
ing these 2 cutoffs, our model was successful in labeling
approximately 80% of patients as either low or high risk,
leaving only 20% of our population in the intermediate-
risk category for which EUS or MRCP would be recommen-
ded. For those endoscopists for whom this rate of
diagnostic ERCP (22%) is unacceptably high, confirmatory
EUS or MRCP can still be applied to those patients with 2
or more risk factors, while avoiding such tests in those
with 1 or fewer risk factors. Similarly, at the very least,
the relative sensitivity and specificity at each cutoff may
be applied on an institution-specific basis to mitigate a po-
tential overutilization of diagnostic ERCP.
There are many strengths to the present study. It is one
of the largest retrospective studies evaluating CDL in this
population with an emphasis on using nearly universally
obtained laboratory testing and imaging for its prediction
model. The model developed had high predictive value
and was validated internally.
There are a few limitations to our study. First, inherent in
our retrospective study design is the reliance upon clinical
diagnosis and ICD coding for the identification of our study
population. As the aim of our study was to develop a preop-
erative decision tool, we opted to use the preoperative clin-
ical impression of the attending surgeon in the identification
of our study population, understanding that there is overlap
in the presenting symptoms of AC, CDL, and other acute
biliary pathology. Second, retained CBD stones may present
several years after cholecystectomy.28 The design of our
study presumed patients not found to have CDL within
our follow-up period did not have CDL, but it is possible
that a few in this group may have asymptomatic CDL,6
6 GASTROINTESTINAL ENDOSCOPY Volume -, No. - : 2019
Chisholm et al
later pass stones spontaneously without symptoms,29 or
may present in the future with symptomatic biliary stones
remaining from their initial cholecystectomy. In addition,
cases presenting to a tertiary care center can select for
a population with higher comorbidities than at other
institutions. This may explain why the average peak
presenting total bilirubin value in our study (1.6 mg/dL)
was higher than the average presenting bilirubin value
seen in other studies of AC.19,24,30 Third, we recognize that
there is significant variation in practice among surgeons
and endoscopists driven by physician preference, practice
patterns, and institutional guidelines. The relatively low
rate (10.4%) of IOC performed in this study may reflect
the preference at our institution for CBD clearance before
surgery, in part due to published data showing that the
presence of CDL at the time of cholecystectomy is an inde-
pendent predictor of CBD injury.31 A practice in which
IOC and intraoperative CBD exploration is more routinely
performed may negate the need for preoperative
evaluation for CDL in this population. However, the rate of
CBD exploration in the United States has decreased
markedly and is associated with increasing rates of
technical adverse events.32,33
In conclusion, in patients with acute cholecystitis, the
presence of concomitant CDL predictably increases the
serum levels of liver indices. Through application of a
multivariable logistic regression, we were able to identify
a simple algorithm to triage patients presenting with acute
cholecystitis to minimize unnecessary testing and expedite
appropriate care. Prospective application and validation of
this algorithm, assessing its effects on length of stay,
resource utilization, and patient outcomes, are warranted.
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Chisholm et al
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Preoperative predictors of choledocholithiasis Chisholm et al

SUPPLEMENTARY TABLE 1. ICD-9 and ICD-10 codes

Diagnosis ICD-9 and/or ICD-10 code

Acute cholecystitis K81.0, K80.00, 575.0

Obstruction of gallbladder K82.0, 575.2
Perforation of gallbladder K82.2, 575.4
Fistula of gallbladder K82.3
Other specified diseases of gallbladder K82.8, 575.8
Other specified disorders of biliary tract K83.8
Cholangitis K83.0
Disease of gallbladder, unspecified K82.9, 575.9
Calculus of gallbladder with acute cholecystitis with obstruction K80.01
Calculus of bile duct with cholecystitis, unspecified, without obstruction K80.40
Calculus of gallbladder with acute and chronic cholecystitis without obstruction K80.12,
Calculus of gallbladder with other cholecystitis, without mention of obstruction K80.10, 574.10
Calculus of gallbladder with chronic cholecystitis with obstruction K80.11, 574.11
Calculus of gallbladder with acute and chronic cholecystitis with obstruction K80.13, 574.01
Calculus of gallbladder with other cholecystitis without obstruction K80.18
Calculus of gallbladder with other cholecystitis with obstruction K80.19
Cholecystitis unspecified 575.1
Chronic cholecystitis 575.11
Acute and chronic cholecystitis 575.12
Calculus of gallbladder with acute cholecystitis without mention of obstruction 574.00
Calculus of bile duct with acute cholecystitis, without mention of obstruction 574.30

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Chisholm et al Preoperative predictors of choledocholithiasis

SUPPLEMENTARY TABLE 2. Demographic and laboratory characteristics of model development cohort and validation cohort

Model development Validation cohort

cohort (n [ 259) (n [ 107) P value

Male, n (%) 148 (40.4) 103 (39.8) 45 (42.1)

Age (years), mean (SD) 52.1 (17.2) 51.4 (17.2) 53.3 (17.5) .33
Imaging studies used, n (%)
US 353 (96.2) 250 (96.2) 103 (97.2) .63
CT 90 (34.5) 62 (23.9) 28 (26.4) .61
HIDA 121 (33.0) 95 (36.5) 26 (24.5) .03
MRI/MRCP 25 (6.8) 19 (7.3) 7 (6.6) .81
EUS 29 (7.9) 19 (7.3) 10 (9.4) .49
Surgical approach, n (SD)
Laparoscopic 283 (77.8) 196 (76.0) 87 (82.1) .27
Open 25 (6.9) 21 (8.1) 4 (3.8)
Converted to open 56 (15.4) 41 (15.9) 15 (14.2)
Preoperative laboratory values (normal values), mean (SD)
AST (8-30 IU/L) 140.7 (326.1) 130.9 (333.5) 161.3 (309.5) .42
ALT (< 35 IU/L) 132.0 (214.8) 122.2 (203.9) 151.7 (237.1) .26
AlkPhos (30-116 IU/L) 148.0 (135.2) 150.3 (149.6) 144.4 (92.7) .65
Total bilirubin (0.2-1.2 mg/dL) 1.6 (1.9) 1.6 (1.9) 1.6 (1.9) .83
Albumin (3.5-4.9 g/dL) 4.2 (0.5) 4.2 (0.5) 4.2 (0.5) .5
INR (< 1.4) 1.2 (0.8) 1.3 (0.9) 1.2 (0.6) .39
Platelet count (150-400  103/mL) 256.7 (87.6) 259.1 (92.4) 251.5 (77.3) .43
WBC (4-10  103/mL) 12.9 (5.5) 12.8 (5.9) 12.8 (4.6) .92
SD, Standard deviation; HIDA, hepatobiliary iminodiacetic acid scan; MRI, magnetic resonance imaging; AST, serum aspartate transaminase; ALT, serum alanine transaminase;
AlkPhos, serum alkaline phosphatase; INR, international normalized ratio; WBC, white blood cell count.

SUPPLEMENTARY TABLE 3. Performance characteristics of multivariable model 1 using the first presenting laboratory value in the validation
cohort

Number of False False Cumulative

predictors Sensitivity Specificity positive negative percentage
Predictors AUROC present (%) (%) (%) (%) below cutoff

First AlkPhos > ULN, 0.86 (0.81-0.92) 0 13 (86.7) 56 (61.5) 35 (72.9) 2 (3.5) 54.7
first ALT > 33 ULN, 1 12 (80.0) 78 (85.7) 13 (52.0) 3 (3.7) 76.4
CBD >6 mm
3 6 (40.0) 89 (97.8) 2 (25.0) 9 (9.2) 92.5
AUROC, Area under the receiver operating curve; AlkPhos, serum alkaline phosphatase; ULN, upper limit of normal; ALT, serum alanine transaminase; CBD, common bile duct.

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