CLINICAL GUIDELINES 405
ACG Clinical Guideline: Diagnosis and Management of
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Biliary Strictures
B. Joseph Elmunzer, MD, MSc1, Jennifer L. Maranki, MD, MSc2, Victoria Gómez, MD3, Anna Tavakkoli, MD, MSc4,5,
Bryan G. Sauer, MD, MSc, FACG6, Berkeley N. Limketkai, MD, PhD, FACG7, Emily A. Brennan, MLIS8, Elaine M. Attridge, MLS9,
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Tara J. Brigham, MLIS, AHIP10 and Andrew Y. Wang, MD6
A biliary stricture is an abnormal narrowing in the ductal drainage system of the liver that can result in clinically and
physiologically relevant obstruction to the flow of bile. The most common and ominous etiology is malignancy, underscoring
the importance of a high index of suspicion in the evaluation of this condition. The goals of care in patients with a biliary
stricture are confirming or excluding malignancy (diagnosis) and reestablishing flow of bile to the duodenum (drainage); the
approach to diagnosis and drainage varies according to anatomic location (extrahepatic vs perihilar). For extrahepatic
strictures, endoscopic ultrasound-guided tissue acquisition is highly accurate and has become the diagnostic mainstay. In
contrast, the diagnosis of perihilar strictures remains a challenge. Similarly, the drainage of extrahepatic strictures tends to
be more straightforward and safer and less controversial than that of perihilar strictures. Recent evidence has provided
some clarity in multiple important areas pertaining to biliary strictures, whereas several remaining controversies require
additional research. The goal of this guideline is to provide practicing clinicians with the most evidence-based guidance on
the approach to patients with extrahepatic and perihilar strictures, focusing on diagnosis and drainage.
KEYWORDS: biliary strictures; obstructive jaundice; extrahepatic strictures; perihiliar strictures; endoscopic ultrasound; guideline
Am J Gastroenterol 2023;118:405–426. https://doi.org/10.14309/ajg.0000000000002190; published online January 17, 2023
INTRODUCTION strictures related to primary sclerosing cholangitis (PSC) is cov-
A biliary stricture is an abnormal narrowing in the ductal drainage ered in a separate American College of Gastroenterology (ACG)
system of the liver. These often result in clinically and physiologically guideline dedicated to this condition (1). Finally, we do not ad-
relevant obstruction to the flow of bile but may not cause symptoms dress surgical or oncological care of malignant strictures, except
or abnormal liver tests early in their course. There are many etiol- where there are endoscopic implications.
ogies of biliary stricture, the most common and ominous of which is Recognizing the potential influence of commercial and in-
malignancy, either primary or metastatic. The 2 principal manage- tellectual conflict of interest on the guideline development pro-
ment priorities in the patient with a biliary stricture are diagnosis and cess, recommendations in this document were made by a diverse
drainage—specifically, the confirmation or exclusion of malignancy group of authors using a systematic process that involved struc-
and the restoration of flow of bile into the duodenum. Because of tured literature searches by librarians and independent appraisal
concrete implications in the approach to diagnosis and drainage, of the quality of evidence by dedicated methodologists, all under
biliary strictures are generally divided according to their anatomic the oversight of the ACG Practice Parameters Committee.
location (extrahepatic, perihilar, or intrahepatic).
The goal of this guideline is to provide clinicians with the most METHODS
evidence-based guidance on the care of patients with extrahepatic The PICO formula—a standardized and validated approach to
and perihilar strictures, focusing on diagnosis and drainage. Al- framing important clinical questions—served as the basis for
though some of the diagnostic principles that are discussed in recommendations in this document. By consensus, the authors
this document may be applied to intrahepatic strictures, this developed PICO (population, intervention, comparator, and
entity is not specifically addressed. Moreover, the management of outcomes) statements pertaining to each aspect of biliary stricture
1
Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, South Carolina, USA; 2Division of Gastroenterology and Hepatology,
Penn State Hershey Medical Center, Hershey, Pennsylvania, USA; 3Division of Gastroenterology, Mayo Clinic Florida, Jacksonville, Florida, USA; 4Division of
Digestive and Liver Diseases, University of Texas Southwestern, Dallas, Texas, USA; 5Department of Population and Data Sciences, University of Texas
Southwestern, Dallas, Texas, USA; 6Division of Gastroenterology and Hepatology, University of Virginia, Charlottesville, Virginia, USA; 7Vatche & Tamar Manoukian
Division of Digestive Diseases, UCLA School of Medicine, Los Angeles, California, USA; 8MUSC Libraries, Medical University of South Carolina, Charleston, South
Carolina, USA; 9Health Sciences Library, University of Virginia, Charlottesville, Virginia, USA; 10Mayo Clinic Libraries, Mayo Clinic Florida, Jacksonville, Florida, USA.
Correspondence: B. Joseph Elmunzer, MD, MSc. E-mail: elmunzer@musc.edu.
Received August 24, 2022; accepted December 13, 2022
© 2023 by The American College of Gastroenterology The American Journal of GASTROENTEROLOGY
Copyright © 2023 by The American College of Gastroenterology. Unauthorized reproduction of this article is prohibited.
, 406 Elmunzer et al.
potential disadvantages, whereas a conditional recommendation
Table 1. Grading of Recommendations, Assessment, (denoted by we suggest) is made when some uncertainty remains
Development, and Evaluation about the balance of benefits and harms. Important clinical
questions that are not amenable to the PICO structure or for
Strength of
which inadequate evidence exists to inform recommendations are
recommendation Criteria
addressed as key concepts. The key concepts are largely based on
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Strong Strong recommendations are offered when indirect evidence and expert opinion. Recommendations with
the desirable effects of an intervention clearly associated quality of evidence and strength levels are listed in
outweigh the undesirable effects. Table 2. Key concepts are listed in Table 3.
Conditional Conditional recommendations are offered
when trade-offs are less certain—either EPIDEMIOLOGY AND ETIOLOGY
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because of low-quality evidence or because The burden of biliary strictures is difficult to estimate because of lack of
evidence suggests that desirable and a specific administrative code. The estimated cost of caring for biliary
undesirable effects are closely balanced. disease in general is $16.9 billion annually in the United States, al-
Quality of evidence Criteria
though this figure includes costs associated with gallbladder disease,
choledocholithiasis, and other (nonobstructive) biliary disorders (2).
High We are very confident that the true effect lies However, of the approximately 57,000 new cases of pancreatic cancer
close to that of the estimate of the effect. each year in the United States, we estimate that at least 60% will cause
Moderate We are moderately confident in the effect obstructive jaundice, resulting in a minimum of 34,000 annual cases of
estimate: The true effect is likely to be close to malignant extrahepatic biliary stricture (3,4). In addition, approxi-
the estimate of the effect, but there is a mately 3,000 cases of malignant perihilar stricture are expected in the
possibility that it is substantially different. United States each year (3). Patients also seek medical attention for
Low Our confidence in the effect estimate is limited: benign strictures due to conditions such as chronic pancreatitis, PSC,
The true effect may be substantially different autoimmune disease, and postcholecystectomy injury. Although the
from the estimate of the effect. exact incidence is not rigorously defined, every gastroenterologist will
encounter biliary strictures with reasonable frequency. The possible
Very low We have very little confidence in the effect
etiologies of biliary stricture are listed in Table 4.
estimate: The true effect is likely to be substantially
different from the estimate of effect.
Factors influencing the strength of the recommendation include the quality of
Key concept
the evidence, clinical and patient-reported outcomes, risk of harm, and costs. 1. Biliary strictures in adults are more likely to be malignant than
benign except in certain well-defined scenarios.
evaluation and treatment. These PICO statements informed the
development of corresponding recommendations. For each
statement, a team of health science librarians with expertise in Summary of evidence
systematic review and clinical practice guideline development The existing literature demonstrates a high likelihood of malignancy
designed search strategies in PubMed (US National Library of as the etiology of a biliary stricture referred for endoscopic evaluation.
Medicine, National Institutes of Health) and, selectively, Web of For example, in a large series of patients with obstructive jaundice due
Science (Clarivate Analytics) and Cochrane Library (Wiley; to extrahepatic stricture (approximately half of whom had an asso-
EBSCO; Ovid). The databases were searched from inception ciated mass on cross-sectional imaging) referred for endoscopic ul-
through various dates in 2020–21. The search strategies used a trasound (EUS)-guided fine-needle aspiration (FNA), malignancy
combination of subject headings (e.g., MeSH in PubMed) and was diagnosed in 73% (5). Similarly, 2 systematic reviews of studies
keywords for each concept. English language restrictions were comparing the diagnostic yield of EUS- and endoscopic retrograde
applied. Search strategies were validated by ensuring the retrieval of cholangiopancreatography (ERCP)-based sampling for suspected
clearly eligible studies provided by the guideline authors. To malignant biliary strictures (with or without a mass on imaging)
identify additional articles, the authors reviewed PubMed’s similar demonstrated a proportion of cancer ranging from 74% to 87% (6,7).
articles and manually searched reference lists of relevant articles. At A recent systematic review of 11 studies evaluating the diagnostic
least 2 authors independently reviewed all potentially relevant ar- accuracy of cholangioscopy-directed biopsies for indeterminate biliary
ticles resulting from the literature search for each PICO statement strictures—those that have undergone a negative initial evaluation via
and selected eligible articles for consideration and formal appraisal. ERCP—reported malignancy in 193 of 356 included patients (54%)
On the basis of eligible articles, the quality of evidence for and (8). Among patients with a high enough suspicion of cancer to merit
strength of each recommendation was appraised by dedicated surgical resection, the fraction of malignant cases has been observed to
methodologists according to the Grading of Recommendations be in the range of 80%–95% (9–11).
Assessment, Development, and Evaluation (GRADE) frame- It is important to recognize that these studies are enriched with
work. In GRADE, the quality of evidence is divided across a patients at higher pretest probability of malignancy because those
spectrum from very low to high depending on the level of con- with obviously benign etiologies (such as an anastomotic stricture
fidence that the true effect is close to the estimated (reported) after liver transplantation) would not have been included. Nev-
effect and how likely further research is to change this level of ertheless, even after accounting for this selection bias, endoscopic
confidence (Table 1). A strong recommendation (denoted in this and surgical series suggest that whenever the etiology is not readily
document by the verbiage we recommend) is made when the apparent (e.g., postoperative stricture, Mirizzi syndrome, or pseu-
benefits of the test or intervention in question clearly outweigh its docyst compressing the bile duct), a stricture is more likely to be
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, ACG Clinical Guideline 407
Table 2. Recommendations with associated quality of evidence and strength levels
Recommendation Quality of evidence Strength level
1. In patients with an extrahepatic biliary stricture due to an apparent or suspected pancreatic Moderate Strong
mass, we recommend EUS with fine-needle sampling (aspiration or biopsy) over ERCP as the
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preferred method of evaluating for malignancy.
2. In patients with an extrahepatic biliary stricture due to an apparent or suspected pancreatic Very low Conditional
mass, we suggest EUS with FNB or EUS with FNA plus ROSE over FNA without ROSE as the
preferred method of evaluating for malignancy.
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3. In patients with suspected malignant perihilar stricture, we recommend multimodality Low Strong
sampling over brush cytology alone at the time of the index ERCP.
4. In patients with an extrahepatic stricture due to a benign condition, we recommend fcSEMS Low Conditional
placement over multiple plastic stents in parallel to reduce the number of procedures required for
long-term treatment.
5. In patients with an extrahepatic stricture due to resectable pancreatic cancer or Low Conditional
cholangiocarcinoma, we suggest against routine preoperative biliary drainage.
In selected patients, including those with acute cholangitis, severe pruritus, very high serum
bilirubin levels, and those undergoing neoadjuvant therapy or experiencing another anticipated
delay to surgery, preoperative biliary drainage is warranted.
6. In patients with a malignant extrahepatic biliary stricture that is unresectable or borderline Moderate Strong
resectable, we recommend SEMS placement over plastic stent placement.
7. In patients with a malignant extrahepatic biliary stricture that is unresectable or borderline Insufficient
resectable, the evidence is insufficient to recommend for or against uSEMS vs fcSEMS placement.
8. In patients with a perihilar stricture due to suspected malignancy, the evidence is insufficient to Insufficient
recommend for or against ERCP vs PTBD.
9. In patients with malignant perihilar stricture, the evidence is insufficient to recommend for or Insufficient
against PS vs uSEMS placement.
10. In patients with a malignant perihilar stricture due to cholangiocarcinoma who are not Low Conditional
candidates for resection or transplantation, we suggest the use of adjuvant endobiliary ablation
(photodynamic therapy or radiofrequency ablation) plus plastic stent placement over plastic stent
placement alone.
11. In patients with a biliary stricture, in whom ERCP is indicated but unsuccessful or impossible, Very low Conditional
we suggest EUS-guided biliary access/drainage over PTBD, based on fewer adverse events, when
performed by an endoscopist with substantial experience in these interventional EUS procedures.
ERCP, endoscopic retrograde cholangiopancreatography; EUS, endoscopic ultrasound; fcSEMS, fully covered self-expanding metallic stent; FNA, fine-needle aspiration;
FNB, fine-needle biopsy; PS, plastic stent; PTBD, percutaneous transhepatic biliary drainage; ROSE, rapid on-site evaluation; SEMS, self-expanding metallic stent; uSEMS,
uncovered self-expanding metallic stent.
malignant than benign, underscoring the importance of a high index improved our diagnostic capabilities with substantially less risk and
of clinical suspicion in the evaluation of this condition. has thus supplanted ERCP in several scenarios. Despite important
advances in the last 2 decades, however, the diagnosis of biliary
DIAGNOSIS strictures without an associated mass remains a major challenge in
A priority of care when evaluating a biliary stricture is safe, accurate, clinical practice (see below).
and expedient diagnosis. In many (but not all) cases, a definitive
diagnosis of cancer will have important implications in surgical and Diagnosis: extrahepatic stricture
oncological decision making and endoscopic biliary stent selection. Recommendation
With rare exception, the diagnosis of malignancy in a biliary stricture
cannot be confirmed or excluded on the basis of noninvasive testing. 1. In patients with an extrahepatic biliary stricture due to an apparent
Studies evaluating various imaging modalities for biliary stricture, or suspected pancreatic mass, we recommend EUS with fine-
such as computed tomography, magnetic resonance imaging, and needle sampling (aspiration or biopsy; FNA/B) over ERCP as the
preferred method of evaluating for malignancy (strong
EUS (without FNA), have reported diagnostic accuracies in the
recommendation, moderate-quality evidence).
range of 60%–80% (12,13). Biomarkers, such as CA 19-9 and CEA,
have proven even less accurate (14–16). Therefore, a definitive tissue
diagnosis is necessary to guide oncologic and endoscopic care in the
large majority of strictures that are not surgically resectable at the Summary of evidence
time of presentation. Traditionally, ERCP has been the mainstay of ERCP-based tissue sampling (via transpapillary brush cytology
tissue acquisition; however, EUS-guided sampling has significantly and forceps biopsies) and EUS-FNA/B are the 2 most commonly
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