Choledocholithiasis - Clinical Manifestations, Diagnosis, and Management
Choledocholithiasis - Clinical Manifestations, Diagnosis, and Management
Choledocholithiasis - Clinical Manifestations, Diagnosis, and Management
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INTRODUCTION
Choledocholithiasis refers to the presence of gallstones within the common bile duct. This topic
will review the clinical manifestations and diagnosis of choledocholithiasis. The treatment of
choledocholithiasis, as well as the epidemiology and the general management of patients with
gallstones, are discussed separately:
EPIDEMIOLOGY
According to the National Health and Nutrition Examination Survey (NHANES III), over 20
million Americans are estimated to have gallbladder disease (defined as the presence of
gallstones on transabdominal ultrasound or a history of cholecystectomy) [1,2]. Cholelithiasis
and cholecystitis are responsible for over 1.4 million annual emergency department visits in the
United States [3]. Approximately 10 to 15 percent of individuals with gallstones will develop
symptomatic gallstone disease over the course of a decade [4]. It has been estimated that 5 to
20 percent of patients have choledocholithiasis at the time of cholecystectomy, with the
incidence increasing with age [5-11]. Of those with symptomatic gallstones, 10 percent will also
have choledocholithiasis and this number increases to 15 percent when patients are presenting
with acute cholecystitis [12].
ETIOLOGY
Primary choledocholithiasis (ie, formation of stones within the common bile duct) typically
occurs in the setting of bile stasis (eg, patients with cystic fibrosis), resulting in a higher
propensity for intraductal stone formation. Older adults with large bile ducts and periampullary
diverticular are also at elevated risk for the formation of primary bile duct stones. Patients with
recurrent or persistent infection involving the biliary system frequently form bile duct stones, a
phenomenon seen most commonly in populations from East Asia. Other causes include
ischemia due to hepatic artery injury, which may occur post-liver transplant. The causes of
primary choledocholithiasis often affect the biliary tract diffusely, so patients may have both
extrahepatic and intrahepatic biliary stones. Intrahepatic stones may be complicated by
recurrent pyogenic cholangitis. (See "Recurrent pyogenic cholangitis".)
Secondary choledocholithiasis results from the passage of gallstones from the gallbladder into
the common bile duct. In Western countries, most cases of choledocholithiasis are secondary to
gallbladder stones.
CLINICAL MANIFESTATIONS
Patients with choledocholithiasis typically present with biliary-type pain and laboratory testing
that reveals a cholestatic pattern of liver test abnormalities (ie, elevated bilirubin and alkaline
phosphatase). Patients with uncomplicated choledocholithiasis are typically afebrile and have a
normal complete blood count and pancreatic enzyme levels. Occasionally, patients are
asymptomatic. In such patients, the diagnosis may be suspected because of abnormal liver
blood tests, abnormalities seen on imaging studies obtained for unrelated reasons, or when an
intraoperative cholangiogram obtained during cholecystectomy suggests the presence of a
common bile duct (CBD) stone. (See "Approach to the patient with abnormal liver biochemical
and function tests", section on 'Patterns of liver test abnormalities'.)
Uncomplicated choledocholithiasis
The pain from choledocholithiasis resolves when the stone either passes spontaneously or is
removed. Some patients have intermittent pain due to transient blockage of the CBD. Transient
blockage occurs when there is retention and floating of stones or debris within the bile duct, a
phenomenon referred to as a "ball-valve" effect.
Since liver tests may be elevated due to a wide variety of etiologies, the positive predictive value
of elevated liver tests is poor [11,14,15]. On the other hand, the negative predictive value of
normal liver tests is high. Thus, normal liver tests play a greater role in excluding
choledocholithiasis than elevated liver tests play in diagnosing stones.
Improving liver blood tests combined with symptom resolution suggests that a patient with
choledocholithiasis has spontaneously passed the gallstone, although it can occur if a stone
ball-valves up into the duct and does not exclude the possibility of more than one stone in the
bile duct.
Complicated choledocholithiasis — The two major complications associated with
choledocholithiasis are pancreatitis and acute cholangitis.
Acute cholangitis — Patients with acute cholangitis may present with Charcot's triad (fever,
right upper quadrant pain, and jaundice) and leukocytosis. In severe cases, bacteremia and
sepsis may additionally lead to hypotension and altered mental status (Reynolds' pentad).
Cholangitis contributes to nearly 2400 deaths per year in the United States [3]. (See "Acute
cholangitis: Clinical manifestations, diagnosis, and management", section on 'Clinical
manifestations'.)
Long-standing biliary obstruction from various causes, including CBD stones, may result in liver
disease that may progress to cirrhosis, a phenomenon referred to as secondary biliary cirrhosis
[1,5]. Although rare in the setting of bile duct stones, secondary biliary cirrhosis may eventually
result in the same cirrhosis-related complications that occur with other etiologies. Relief of
biliary obstruction has been shown to result in regression of liver fibrosis in patients with
secondary biliary cirrhosis in the setting of chronic pancreatitis and choledochal cysts [6,7]. It is
likely, but not known, whether stone removal results in similar improvement in liver disease in
patients with choledocholithiasis-induced secondary biliary cirrhosis.
DIFFERENTIAL DIAGNOSIS
Patients with choledocholithiasis typically present acutely with sudden onset of pain that may
be stuttering and progress to prolonged episodes of pain. On the other hand, the episodes of
pain in patients with uncomplicated gallstone disease, sphincter of Oddi dysfunction, or
functional gallbladder disorder typically last less than six hours and often occur intermittently.
In addition, patients with uncomplicated gallstone disease or functional gallbladder disorder
should have normal laboratory tests and imaging (though patients with sphincter of Oddi
dysfunction may have bile duct dilation and elevations in the alanine aminotransferase,
aspartate aminotransferase, and alkaline phosphatase that normalize between attacks).
Endoscopic ultrasound or magnetic resonance cholangiopancreatography may be required to
identify choledocholithiasis. (See "Overview of gallstone disease in adults" and "Functional
gallbladder disorder in adults".)
Like patients with choledocholithiasis, patients with acute cholecystitis may have prolonged
episodes of pain that start suddenly. However, patients with acute cholecystitis generally do not
have significantly elevated (greater than three times the upper limit of normal) bilirubin or
alkaline phosphatase levels unless there is a secondary process causing cholestasis. In addition,
abdominal imaging in acute cholecystitis typically reveals a normal CBD, gallbladder wall
thickening, and a sonographic Murphy's sign. (See "Acute calculous cholecystitis: Clinical
features and diagnosis".)
Laboratory findings — If not already done, we also obtain a complete blood count to look for
leukocytosis (which may suggest acute cholangitis has developed), liver tests, and pancreatic
enzyme levels to evaluate for concurrent pancreatitis. (See "Management of acute pancreatitis",
section on 'Management of underlying predisposing conditions'.)
Transabdominal ultrasound — The initial imaging study of choice in patients with suspected
CBD stones is a transabdominal ultrasound of the right upper quadrant. Transabdominal
ultrasound can evaluate for cholelithiasis, choledocholithiasis, and CBD dilation. It is readily
available, noninvasive, permits bedside evaluation, and provides a low-cost means of evaluating
the CBD for stones.
A dilated CBD on transabdominal ultrasound is suggestive of, but not specific for,
choledocholithiasis [9,11,14]. A cutoff of 6 mm is often used to classify a duct as being dilated,
however, this may change with advancing age or with a history of cholecystectomy [17].
However, using a cutoff of 6 mm may miss CBD stones [22]. One study of 870 patients
undergoing cholecystectomy found that stones were often detected in patients whose ducts
would have been classified as "nondilated" using the 6 mm cutoff [23]. In addition, the
probability of a stone in the CBD increased with increasing CBD diameter:
Conversely, because the diameter of the CBD increases with age, older adults may have a
normal duct with a diameter that is >6 mm. Following cholecystectomy, the CBD may dilate to
10 mm. (See 'Prior cholecystectomy' below.)
● High risk – Patients with any one of the following are considered at high risk for a CBD
stone and have an estimated probability of having a CBD stone of >50 percent:
● Intermediate risk – Patients with any one of the following are considered to be at
intermediate risk with an estimated 10 to 50 percent probability of having a CBD stone:
● Low risk
• No predictors present.
These risk criteria have been proposed by the ASGE in their 2019 guidelines on the role of
endoscopy in the evaluation and management of choledocholithiasis. They differ from the 2010
ASGE guidelines where either a serum bilirubin >4 mg/dL (68 micromol/L) or a dilated CBD on
ultrasound >6 mm in a patient with a gallbladder in situ were considered high-risk predictors
[17]. In a very large cohort of 2724 patients using a more restrictive high-risk criteria that
required both a serum bilirubin >4 mg/dL and bile duct dilation, this improved the specificity of
finding a CBD stone at the time of ERCP from 74 to 94 percent [24]. (See 'Subsequent evaluation
and management' below.)
SUBSEQUENT EVALUATION AND MANAGEMENT
Choice of treatment — In patients with acute cholangitis, and in patients with both ongoing
evidence of biliary obstruction and acute pancreatitis, preoperative endoscopic retrograde
cholangiopancreatography (ERCP) with stone removal is indicated; if ERCP is unsuccessful,
endoscopic ultrasound-guided rendezvous may facilitate access for ERCP [25]. If endoscopic
drainage is not feasible due to altered anatomy or other reasons, the patient may undergo
percutaneous biliary drainage ( algorithm 1). (See 'Concomitant acute pancreatitis' below.)
For all other patients at high risk for having common bile duct (CBD) stones, options include
ERCP with stone removal followed by elective cholecystectomy or cholecystectomy with
intraoperative ERCP or CBD exploration/postoperative ERCP [26]. For most patients, the choice
of treatment depends on available expertise and patient preference.
In the United States at least, the use of ERCP is rising and the use of surgical CBD exploration is
declining [27,28]. Outcomes for laparoscopic versus endoscopic treatment have been compared
in randomized trials and observational studies [29-35]. A 2018 network meta-analysis aimed to
determine the optimal approach for the treatment of gallstone disease with
choledocholithiasis, comparing preoperative ERCP plus laparoscopic cholecystectomy,
laparoscopic cholecystectomy with laparoscopic CBD exploration, laparoscopic cholecystectomy
plus intraoperative ERCP, and laparoscopic cholecystectomy plus postoperative ERCP [36].
Twenty trials with 2489 patients were included. Same-session laparoscopic cholecystectomy
with intraoperative ERCP was the most successful, safest, and had the shortest length of
hospital stay. However, intraoperative ERCP may not be feasible at some centers. Although
laparoscopic cholecystectomy plus laparoscopic CBD exploration had the shortest operative
time, least total cost, and lowest acute pancreatitis rate, it had a higher risk of biliary leak. It
should be noted that some of the intraoperative ERCP studies used a rendezvous technique
where a transcystic guidewire was passed laparoscopically across the major papilla, which
would then facilitate atraumatic biliary ERCP cannulation, potentially explaining higher rates of
success compared with preoperative and postoperative ERCP. However, this technique is not
universal among centers. (See "Surgical common bile duct exploration".)
Preoperative ERCP and elective cholecystectomy — ERCP can diagnose and remove CBD
stones ( image 2). The sensitivity of ERCP for choledocholithiasis is estimated to be 80 to 93
percent, with a specificity of 99 to 100 percent [37,38]. However, ERCP is invasive, requires
technical expertise, and is associated with complications such as pancreatitis, bleeding, and
perforation. Endoscopic techniques for CBD stone clearance include sphincterotomy and/or
balloon dilation of the ampulla followed by stone extraction using baskets and extraction
balloons as well as mechanical lithotripsy. These techniques are discussed in detail separately.
(See "Endoscopic management of bile duct stones".)
Additional imaging (MRCP or EUS) — Patients at intermediate risk may be considered for
cholecystectomy with intraoperative cholangiography or additional imaging to confirm the
presence of a CBD stone prior to an ERCP. MRCP is often the preferred imaging modality for
CBD stones in patients at intermediate risk ( image 3) [39,40]. Deciding which test should be
performed depends on various factors such as ease of availability, cost, patient-related factors,
and the suspicion for a small stone ( table 2). If an ERCP can be performed at the same
setting as the EUS, performing EUS may facilitate therapy by ERCP, especially if the clinical
suspicion for a CBD stone is high ( image 4). A meta-analysis from 2017 showed that the
pooled sensitivity of EUS was higher than MRCP. The pooled sensitivity and specificity of EUS
was 97 percent and 90 percent, respectively, and for MRCP was 87 percent and 92 percent,
respectively [41]. The lower sensitivity of MRCP may be due to difficulty detecting small stones
[<6 mm, ( image 5)] [42]. (See 'Intermediate risk of CBD stone' above.)
CBD stone visualized — If the MRCP or EUS is positive for a CBD stone, patients should
undergo either preoperative ERCP and elective cholecystectomy or laparoscopic
cholecystectomy with intraoperative ERCP, CBD exploration, or postoperative ERCP. (See
'Laparoscopic cholecystectomy with intraoperative CBD exploration or postoperative ERCP'
above.)
CBD stone not visualized — If the MRCP is negative for a CBD stone, but the suspicion
for a CBD stone remains moderate to high (eg, in a patient whose laboratory tests are not
improving), EUS is an appropriate next step. In many centers, the endoscopist performing the
EUS can perform an ERCP during the same session if a stone is found.
In all other patients with an MRCP that is negative for a CBD stone, an elective cholecystectomy
(provided gallstones or biliary sludge were demonstrated on preoperative imaging) can be
performed.
● If intraoperative imaging is negative for a CBD stone, the patient can proceed to elective
cholecystectomy.
Low risk of CBD stone — Low-risk patients are estimated to have a <10 percent probability of
having a CBD stone [17]. (See 'Assess risk of choledocholithiasis' above.)
Special circumstances
Concomitant acute pancreatitis — Patients with both acute pancreatitis and acute
cholangitis should undergo urgent (<24 hours) ERCP [17]. (See "Management of acute
pancreatitis", section on 'Gallstone pancreatitis'.)
In patients with gallstone pancreatitis and persistent obstruction without cholangitis, urgent
ERCP (within 24 hours) is not indicated. In such patients, therapeutic ERCP can be performed
either before the cholecystectomy, if there is a strong suspicion of a stone in the bile duct, or if
confirmed by other imaging. ERCP can also be considered in patients who will be discharged
from the hospital before cholecystectomy, which is typically due to necrotizing pancreatitis.
However, ERCP in the presence of sterile necrotizing pancreatitis may introduce risk of early
infection of the necrosis, which can be highly morbid [50]
In patients with acute pancreatitis but equivocal evidence of bile duct stones (eg, improving
liver enzyme tests and/or improvement or resolution of pain), MRCP or EUS followed by ERCP
only if the EUS/MRCP reveals a CBD stone is an attractive option because it can detect CBD
stones but is not associated with pancreatitis.
Issues related to ERCP in patients with acute biliary pancreatitis are discussed elsewhere. (See
"Management of acute pancreatitis", section on 'Endoscopic retrograde
cholangiopancreatography'.)
Following cholecystectomy, the CBD may dilate to 10 mm or more, especially in older adult
patients. In such patients, transabdominal ultrasound is less helpful because a dilated CBD seen
on ultrasound may be the result of a CBD stone, or it may be the result of the cholecystectomy.
One approach to patients who have undergone a prior cholecystectomy and who present with
biliary-type pain and liver test abnormalities, but in whom there is uncertainty following a
transabdominal ultrasound as to the presence of a bile duct stone, is to proceed with an MRCP
or EUS to confirm the presence of a stone. If a stone is absent, it is important to consider
alternative etiologies including sphincter of Oddi dysfunction. (See 'Differential diagnosis'
above.)
Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Cholecystitis and other
gallbladder disorders" and "Society guideline links: Gallstones" and "Society guideline links:
Biliary infection and obstruction".)
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the
Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade
reading level, and they answer the four or five key questions a patient might have about a given
condition. These articles are best for patients who want a general overview and who prefer
short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more
sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading
level and are best for patients who want in-depth information and are comfortable with some
medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print
or e-mail these topics to your patients. (You can also locate patient education articles on a
variety of subjects by searching on "patient info" and the keyword(s) of interest.)
● Beyond the Basics topics (see "Patient education: ERCP (endoscopic retrograde
cholangiopancreatography) (Beyond the Basics)")
• High risk – Patients with any one of the following are considered at high risk for a
common bile duct (CBD) stone and have an estimated probability of having a CBD
stone of >50 percent:
• Intermediate risk – Patients with any one of the following are considered to be at
intermediate risk with an estimated 10 to 50 percent probability of having a CBD stone:
• Low risk
- No predictors present.
• Patients at high risk for having common bile duct stones and with an intact gallbladder
generally proceed to endoscopic retrograde cholangiopancreatography (ERCP) with
stone removal, followed by elective cholecystectomy, or they undergo cholecystectomy
with intraoperative cholangiography, followed by intraoperative or postoperative ERCP;
where expertise is available, laparoscopic common bile duct exploration can be
performed. Precholecystectomy ERCP followed by cholecystectomy is appropriate in
patients with acute cholangitis, in those with ongoing evidence of biliary obstruction
and acute pancreatitis. (See 'High risk of common bile duct stone' above.)
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Topic 13922 Version 39.0
GRAPHICS
Pregnancy
End-stage liver disease
* Serum bilirubin concentration is usually less than 4 mg/dL (68 mmol/L) in the absence of
underlying liver disease.
¶ The hyperbilirubinemia induced by drugs usually resolves within 48 hours after the drug is
discontinued.
CBD: common bile duct; ERCP: endoscopic retrograde cholangiopancreatogram; EUS: endoscopic ultrasoun
IOC: intraoperative cholangiogram; IOU: intraoperative ultrasonography; MRCP: magnetic resonance
cholangiopancreatogram.
* A common bile duct measuring more than 6 mm in a patient with a gallbladder in situ and more than 8
mm in those that have had a cholecystectomy.
¶ Refer to UpToDate content on surgical common bile duct exploration and acute pancreatitis.
Δ If no stone is visualized on MRCP but suspicion for a CBD stone remains moderate to high (eg, in a patient
whose laboratory tests are not improving), EUS is an appropriate next step.
References:
1. ASGE Standards of Practice Committee, Buxbaum JL, Abbas Fehmi SM, et al. ASGE guideline on the role of endoscopy in the
evaluation and management of choledocholithiasis. Gastrointest Endosc 2019; 89:1075.
MRCP
Advantages
Noninvasive
Disadvantages
Time consuming
False-positive studies (eg, intraductal artifacts such as air or blood, image reconstruction artifacts,
motion artifacts)
False-negative studies (eg, stones in dilated CBD or stones <5 mm in the distal duct may not be
visualized well)
EUS
Advantages
Very high resolution (0.1 mm) compared with MRCP (1.5 mm)
Dynamic imaging allowing manipulation and magnification of image for better visualization
ERCP can potentially be performed in the same setting for stone removal
Disadvantages
Risks associated with sedation (eg, cardiopulmonary compromise) and endoscopy (eg, bleeding
and perforation)
Not possible or limited role in altered anatomy (eg, pyloric stenosis, Roux-en-Y bypass)
CBD: common bile duct; ERCP: endoscopic retrograde cholangiopancreatography; EUS: endoscopic
ultrasound; MRCP: magnetic endoscopic retrograde cholangiopancreatography.