Choledocholithiasis and cholangitis

How can I be sure that the patient has choledocholithiasis and/or cholangitis?

Signs and symptoms

Typical signs and symptoms of choledocholithiasis include abdominal pain that is episodic but constant in character, localized in the right upper quadrant, epigastrium, or both and may radiate to the right side; nausea and vomiting are common and tend not to relieve the pain; anorexia; icterus; and dark urine and acholic stool can be seen in complete or near-complete biliary obstruction.

Cholangitis can present with icterus, abdominal pain, and fever (Charcot’s triad); when coupled with hypotension and mental status changes, it is known as Reynolds’ pentad and denotes more severe disease.

Usual constellation of clinical

Choledocholithiasis can present with five constellations of clinical features: asymptomatic, biliary colic (episodic but constant right upper quadrant or epigastric abdominal pain, nausea, vomiting, anorexia), obstructive jaundice (scleral icterus, dark urine, acholic stool), cholangitis (fever, abdominal pain, jaundice, hypotension, mental status changes), and pancreatitis (constant epigastric pain radiating to the back, nausea, vomiting, anorexia).

A tabular or chart listing of features and signs and symptoms

Are there pathognomonic or characteristic features?

There are no pathognomonic features for choledocholithiasis and cholangitis. The patients can present with one or more of these constellation of symptoms in various combinations, which can make the diagnosis difficult.

Liver chemistries may be elevated but can also be completely normal. A fluctuating pattern of liver chemistries is typical. Liver chemistry elevation is due to impediment of biliary flow and, early in the course of obstruction, the predominant pattern is elevation of the transaminases followed later by the elevation of the alkaline phosphatase and, finally, bilirubin. Liver chemistries can rapidly decline after passage of stones. Rapidly alternating elevation and decrease of liver chemistries can be seen with sequential passage of stones or of the floating of stones up and down the main bile duct, causing intermittent obstruction (ball valve effect).

Less common clinical presentations

Patients can be asymptomatic, with or without the elevation of liver chemistries. (See Table I for signs, symptoms, and other features of choledocholithiasis and cholangitis, among others.)

Table I.

	Choledocholithiasis	Cholangitis	Ampullary tumor	Biliary stricture	Cholangiocarcinoma	Cholecystitis	Spasm of SOD
Symptoms	Asymptomatic,biliary colic, orabnormal liver chemistry	Abdominal pain, fever, or jaundice. Mental status changes	Asymptomatic, weight loss, jaundice, or abdominal pain	Related to cause. Jaundice, fever with chills	Painless jaundice	Biliary colic usually lasting >6 hours, nausea	Abdominal pain
Signs	Jaundice,abdominal tenderness	Fever, right upper quadrant tenderness, jaundice, hypotension, or peritoneal signs	Jaundice, palpable gall bladder	Jaundice, stigmata of disease contributing to formation of stricture	Jaundice, palpable gallbladder, weight loss	Fever, right subcostal tenderness on inspiration (Murphy’s sign), palpable gallbladder, mild jaundice	Abdominal tenderness, abnormal liver chemistries or amylase/lipase
Other features	Obstructive jaundice,intermittent elevation of liver chemistries	Cholestasis, leucocytosis, positive blood cultures	Cholestasis, pancreatitis, weight loss	Cholestasis, cholangitis, moderate elevation of CA 19-9	Cholestasis, weight loss, elevated CA 19-9	Leucocytosis,abnormal liver chemistries	Abnormal liver chemistries or elevated amylase/lipase, bile duct dilation

How can I confirm the diagnosis?

What tests should be ordered first?

Several modalities exist for the evaluation of bile duct stones (Freitas et al. 2006). The noninvasive ones should be considered first.

Plain abdominal films are insensitive in detecting choledocholithiasis, but, in rare instances, they can visualize calcified stones or can detect air in the biliary tree. Computed tomography (CT) can detect bile duct dilation but is suboptimal to evaluate for bile duct stones. Transabdominal ultrasound is a good test to use for evaluating for gallbladder stones and bile duct dilation; however, it is not very sensitive for main bile duct stones.

Magnetic resonance cholangiopancreatography (MRCP) is a very good test for evaluation of main bile duct stones because it affords an excellent noninvasive visualization of the biliary tree. MRCP image quality can significantly vary from institution to institution and is prone to motion artifact. MRCP sensitivity is lower for smaller stones.

Endoscopic ultrasound (EUS) is a minimally invasive procedure and has higher sensitivity than MRCP, but it is not widely available on an urgent basis, requires sedation, and is operator dependent (Verma et al. 2006; McMahon 2008). Air in the biliary tree seen on imaging is suggestive of choledochoenteric fistula or in the right clinical setting (fever, jaundice, abdominal pain, hypotension, mental status changes) for cholangitis.

What tests should be used to confirm initial tests?

Choledocholithiasis detected on radiologic imaging usually does not warrant additional confirmatory testing. If the results of the initial radiologic evaluation are equivocal, EUS can be used for confirmation purposes.

What tests are useful if the diagnosis is still in doubt?

If the diagnosis is still in doubt, EUS should be considered first because of its high sensitivity and specificity.

ERCP is considered the gold standard for the diagnosis of choledocholithiasis and can also provide therapy at the same time. However, ERCP is invasive, requires moderate to deep sedation, and is associated with significant morbidity (5 to 20%).

Percutaneous cholangiogram is an option in patients with altered gastric anatomy, previously failed ERCP, or who are too unstable to undergo ERCP.

Intraoperative cholangiogram can be used for the diagnosis of choledocholithiasis in patients with indications for cholecystectomy and suspicion for main bile duct stones.

A diagnostic algorithm

If symptoms and signs suggest biliary obstruction, liver chemistries and a transabdominal ultrasound are usually done first. Further evaluation is based on the degree of clinical suspicion for bile duct stones.

Clinical predictors of choledocholithiasis can be classified in four groups:

Very strong predictors: bile duct stone visualized on transabdominal US, clinical ascending cholangitis, or serum bilirubin higher than 4 mg/dL;

Strong predictors: serum bilirubin level at 1.8-4 mg/dL or a dilated bile duct (>7 mm in patients with gallbladder in situ);

Moderate predictors: abnormal liver biochemical tests other than bilirubin, age older than 55 years, and gallstone pancreatitis;

Low predictors: normal liver chemistries, normal size bile duct.

The diagnosis is confirmed based on the predictors for choledocholithiasis:

– Patients with very strong predictors are evaluated with ERCP;

– Patients with strong predictors are usually evaluated by MRCP or EUS, but ERCP can also be considered;

– Patients with moderate predictors are evaluated by MRCP or EUS; and

– Patients with low predictors usually do not require further evaluation but can be evaluated with intraoperative cholangiogram if cholecystectomy is otherwise medically indicated.

Tabular listing of laboratory tests, results, and suggested action

For a listing of laboratory tests, results, and suggested action, see
Table II.

Table II.

Test	Results	Action
Liver chemistries	Elevated	Transabdominal US
Transabdominal US	Positive for choledocholithiasis	ERCP with sphincterotomy and extraction
	Negative for choledocholithiasis;high pretest probability	MRCP or EUS based on patient preference and availability
MRCP or EUS	Positive for choledocholithiasis	ERCP with sphincterotomy and extraction
	Negative for choledocholithiasis	Cholecystectomy with intraoperative cholangiogram
Intraoperative cholangiogram	Positive for choledocholithiasis	Bile duct exploration or perioperative ERCP or postoperative ERCP

What other diseases, conditions, or complications should I look for in patients with choledocholithiasis and/or cholangitis?

Major risk factors for patients with choledocholithiasis and cholangitis

– Age (>40)
– Female sex
– Obesity
– Pregnancy
– Drugs, such as oral contraceptive pills, clofibrate, ceftriaxone
– Rapid weight loss
– Medical conditions, such as diabetes, cirrhosis, Crohn’s disease, or chronic hemolysis
– Infection with Clonorchis sinensis increases the chances of developing gallstones and subsequent choledocholithiasis

Diseases that may occur with choledocholithiasis and cholangitis

– Acute cholecystitis may occur with choledocholithiasis.
– Bile duct strictures can be seen due to persistent inflammation secondary to choledocholithiasis.

Commonly encountered complications

Acute cholangitis from bacterial translocation and pancreatitis are two major complications. Other complications that may be seen are biliary stricture, intrahepatic biliary stones, and secondary biliary cirrhosis (
Table III).

Table III.

Pancreatitis

Ascending cholangitis

Bile duct stricture

Secondary biliary cirrhosis

Intrahepatic biliary stones

What is the right therapy for the patient with choledocholithiasis and/or cholangitis?

Choledocholithiasis

Treatment for choledocholithiasis depends on the setting in which common bile duct stones are encountered.

ERCP with stone extraction is the first choice.

If the patient is too unstable for the sedation required for ERCP, a percutaneous cholangiogram for biliary decompression is usually done. If the bile duct stones are discovered at the time of laparoscopic cholecystectomy on intraoperative cholangiogram, the two therapeutic options include laparoscopic bile duct exploration or postoperative ERCP.

At present, no sufficient comparative data are available to strongly recommend one of these options as a first-line therapy and, therefore, the choice depends on local expertise; however, in general, postoperative ERCP is favored. Open bile duct exploration has fallen out of favor due to the associated higher morbidity and mortality.

Cholangitis

Treatment of cholangitis depends on the patient status. ERCP is the first choice, but in unstable patients, percutaneous transhepatic cholangiogram can provide biliary decompression.

Options, lifestyle, medical endoscopic surgery, and other estimates of efficacy

Lifestyle modifications to reduce the incidence or recurrence of gallstones include eating well balanced meals with some fat to ensure emptying of the gallbladder. Diets high in fiber and calcium and low in saturated fat reduce the formation of gallstones. Rapid weight loss should be avoided.

Treatment with bile acids (chenedeoxycholic acid/ursodeoxycholic) has fallen out of favor due to low response rate, high costs, and stone recurrence after discontinuation of the therapy.

Statins might help by decreasing biliary cholesterol secretion. They do not affect gallstone formation or dissolution and cannot be recommended yet for therapy of gallstone disease.

Other agents such as monoterpenes or contact dissolution using solvents, although available, are not very widely used.

Endoscopic therapy with ERCP and sphincterotomy with balloon extraction offer the best treatment for choledocholithiasis, although, occasionally, smaller stones can be missed.

Laparoscopic or open cholecystectomy with bile duct exploration can be performed in cases where ERCP is unavailable or choledocholithiasis is visualized during surgery.

What is the most effective initial therapy?

The most effective initial therapy includes the following:

– ERCP with stone extraction is the treatment of choice.

– Percutaneous cholangiography offers a temporizing measure in patients too sick to undergo ERCP.

– Once the bile duct is cleared of stones and if the gallbladder is still in situ, a cholecystectomy should be considered.

Listing of usual initial therapeutic options, including guidelines for use, along with expected results of therapy.

This includes the following:

– ERCP with stone extraction is usually the first choice of therapy for choledocholithiasis and cholangitis.

– If the initial sphincterotomy is small, an extension of the initial sphincterotomy can be performed.

– If the gallstone is too large to be extracted through the existing sphincterotomy, which cannot be extended further due to risk of perforation, a large size balloon dilation (<10 mm) of the sphincterotomy site can be performed.

– If the gallstone still cannot be extracted, other options include the use of mechanical lithotripsy, cholangioscopy with electrohydraulic (EHL) or laser lithotripsy, or extracorporeal shock wave lithotripsy (ESWL).

– In patients in whom all bile duct stones cannot be removed, placement of a biliary stent offers means of drainage and decreases the risk of cholangitis from obstruction secondary to either a stone or edema from instrumentation during the ERCP.

– In some patients with recurrent stones, multiple ERCP procedures may need to be performed.

– For patients too sick to undergo ERCP, emergent biliary decompression is performed through a percutaneous cholangiogram.

– If interventional radiology is unavailable or if the patient is coagulopathic, an ERCP without sphincterotomy but with placement of a biliary stent offers a temporizing measure.

A listing of a subset of second-line therapies, including guidelines for choosing and using these salvage therapies

Side effects or complications to be expected from therapy

Complications arising from procedures related to bile duct stone removal can be grouped into those associated with endoscopic retrieval of bile duct stones and those related to endoscopy in general.

The most common complication from ERCP is pancreatitis (approximately 5%). Other complications include perforation of the duodenum or bile duct, transmission of infection, or bleeding, especially in patients who have some underlying coagulopathy.

Complications related to any endoscopy are those related to sedation, such as cardiovascular or pulmonary instability or aspiration.

Complications can also arise from passage of the endoscope, such as esophageal or duodenal perforation.

Electrosurgical hazards include thermal burns, perforation, bleeding (if adequate coagulation is not achieved), and cardiac arrhythmias in patients with defibrillators.

Long-term complications include papillary stenosis, recurrent stones, cholecystitis, or cholangitis without choledocholithiasis.

Listing of these, including any guidelines for monitoring side effects.

Patients are asked to fast from the night before the procedure to until 6 to 8 hours after the procedure to decrease the risk of aspiration.

Careful monitoring of the patient after endoscopic retrieval of stones is essential as ERCP and sphincterotomy are complex procedures and most complications usually manifest within 6 hours after the ERCP is performed, although pancreatitis can develop up to 24 hours post procedure.

Pancreatitis. Patients may complain of abdominal pain after the procedure. This may be related to gaseous distension; however, continuous pain requiring analgesics should alert the clinician that the patient may be developing pancreatitis. Patients are then vigorously hydrated, placed on intravenous analgesics, and admitted for observation. Amylase and lipase levels, as well as a baseline hematocrit and basic metabolic panel, should be checked.

Bleeding. Pre-procedure platelet count and INR (international normalized ratio) should be routinely checked before endoscopic therapy of bile duct stones, especially in patients on anticoagulation, those with bleeding diathesis, or patients with cirrhosis. Most bleeding, which is seen during endoscopic sphincterotomy, can be stopped during the procedure. Patients at high risk of bleeding post-procedure usually need to be admitted to the hospital and their hematocrit monitored.

Infection. This is usually due to manipulation of the biliary tree or occurs in patients in whom prosthetic cardiac valves are present. Such patients in whom adequate biliary drainage is not achieved usually benefit from antibiotic coverage. Transmission of infection due to contaminated endoscopic equipment is rare if adequate disinfection procedures are followed.

Neck, chest, or abdominal discomfort with severity out of proportion to expected levels warrants imaging, usually with a CT scan, to rule out a perforation.

A therapeutic algorithm

– High likelihood of biliary stones based on above predictors: proceed with preoperative ERCP.
– Intermediate likelihood of biliary stones: preoperative EUS or MRCP and, if positive, proceed to ERCP. If ERCP is unavailable or results are equivocal, cholecystectomy with intraoperative cholangiogram can be performed.
– If positive for choledolithiasis, then either bile duct exploration intraoperatively or post-operative ERCP can be done for stone extraction.
– Patients with low likelihood of choledocholithiasis can proceed directly to cholecystectomy.

How should I monitor the patient with choledocholithiasis and/or cholangitis?

How should complications be monitored?

Patients with choledocholithiasis may be asymptomatic and may be found incidentally when imaging is performed for other reasons. Alternatively, they may have epigastric or right upper quadrant pain. Liver tests abnormalities are seen, with serum AST and ALT being elevated early on. Eventually, serum bilirubin, alkaline phosphatase, and GGT start rising in a cholestatic pattern.

Elevated white blood cell count or fever indicates cholangitis.

How should the progress of stages of disease be monitored?

– Most cases of uncomplicated choledocholithiasis are monitored with serum liver tests and complete blood count until therapy is performed.
Increasing elevations of liver tests in a cholestatic pattern indicate ongoing obstruction, whereas leucocytosis indicates an onset of an infectious process, such as cholangitis due to biliary obstruction.
– Elevations of amylase and lipase with abdominal pain and suspected choledocholithiasis suggest biliary pancreatitis.

Initial investigation for suspected choledocholithiasis begins with liver chemistries and an ultrasound, which is noninvasive and inexpensive. It is not very sensitive for evaluation of the distal bile duct, which tends to get obscured by gas. If results of an ultrasound are inconclusive, an MRCP or EUS, based on availability and patient and healthcare provider preferences, should be performed. ERCP is largely used for therapeutic purposes. Similarly, whereas percutaneous cholangiography can be used for diagnosis of choledocholithiasis, its role is largely limited to therapy because of its invasive nature.

Monitoring recommendations

In suspected choledocholithiasis, initial evaluation involves evaluation of liver chemistries and transabdominal ultrasound. Normal liver chemistries have a high negative predictive value. If liver tests are abnormal and transabdominal US reveals a stone in the bile duct, patients can proceed to therapeutic ERCP.

If ERCP is not available, either surgical evacuation of bile duct stones or in emergent conditions, percutaneous cholangiography offers temporary biliary decompression. Until therapy is achieved, patients are monitored with daily liver chemistries, CBC, and, in the right setting, amylase and lipase.

What's the evidence?

Freitas, ML, Bell, RL, Duffy, AJ. “Choledocholithiasis: evolving standards for diagnosis and management”. World J Gastroenterol. vol. 12. 2006 May 28. pp. 3162-7. (This article describes different modalities used in the diagnosis of choledocholithiasis.)

Verma, D, Kapadia, A, Eisen, GM, Adler, DG. “EUS vs MRCP for detection of choledocholithiasis”. Gastrointest Endosc. vol. 64. 2006 Aug. pp. 248-54. (Systematic review comparing EUS and MRCP, and found both of them to be equally effective.)

McMahon, CJ. “The relative roles of magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound in diagnosis of common bile duct calculi: a critically appraised topic”. Abdom Imaging. vol. 33. 2008 Jan-Feb. pp. 6-9. (Looks at primary and secondary evidences for the use of MRCP and EUS and concludes that MRCP should be done first and then EUS if MRCP is negative and pretest probability is high.)

Maple, JT, Ben-Menachem, T, Anderson, MA. “The role of endoscopy in the evaluation of suspected choledocholithiasis”. Gastrointest Endosc. vol. 71. 2010 Jan. pp. 1-9. (ASGE guidelines on the role of endoscopy in choledocholithiasis.)

Feldman, M, Friedman, LS, Brandt, LJ. “Sleisenger and Fordtran's Gastrointestinal and Liver Disease. Pathophysiology, Diagnosis, and Management”. 2010.

Petrov, MS, Savides, TJ. “Systematic review of endoscopic ultrasonography versus endoscopic retrograde cholangiopancreatography for suspected choledocholithiasis”. Br J Surg. vol. 96. 2009 Sept. pp. 967-74. (Systematic review explaining the importance of EUS in preventing unnecessary ERCP, thus decreasing procedural complications.)

Williams, EJ, Green, J, Beckingham, I. “Guidelines on the management of common bile duct stones (CBDS)”. Gut. vol. 57. 2008. pp. 1004-21. (A good article: provides guidelines and compares different approaches to choledocholithiasis.)

Rubin, RA, Kowalski, TE, Khandelwal, M, Malet, PF. “Ursodiol for hepatobiliary disorders”. Ann Intern Med. vol. 121. 1994. -207. (Article looks at the use of ursodiol.)

Wojtun, S, Gil, J, Gietka, W, Gil, M. “Endoscopic sphincterotomy for choledocholithiasis: a prospective single-center study on the short-term and long-term treatment results in 483 patients”. Endoscopy. vol. 29. 1997 May. pp. 258-65. (Evaluates the efficacy and safety of sphincterotomy for choledocholithiasis and considers sphincterotomy safe procedure for choledocholithiasis.)

Bergman, JJ, Rauws, EA, Fockens, P. “Randomised trial of endoscopic balloon dilation versus endoscopic sphincterotomy for removal of bile duct stones”. Lancet. vol. 349. 1997 Apr 19. pp. 1124-9. (Finds that balloon dilation does not increase the risk of pancreatitis and is a useful adjunctive therapy in patients at risk of bleeding. It also decreases long-term complications associated with endoscopic sphincterotomy.)

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