Residency · Residency · Gastroenterology
Biliary Disorders - Choledocholithiasis and Cholangitis
Gallstone Disease -- Overview
Types of Gallstones
Gallstones are classified into three major types based on their composition and pathogenesis. Cholesterol stones account for approximately 80% of gallstones in Western countries and form when bile becomes supersaturated with cholesterol, exceeding the solubilizing capacity of bile salts and phospholipids. Risk factors for cholesterol stone formation include obesity, rapid weight loss, pregnancy, estrogen use, fibrate medications, Native American ethnicity, and family history. These stones are typically yellow-green, often solitary or few in number, and may contain a mixture of cholesterol and other bile components.
Pigment stones are subdivided into two distinct types. Black pigment stones are composed primarily of calcium bilirubinate polymers and form in the gallbladder in association with chronic hemolysis (sickle cell disease, hereditary spherocytosis, prosthetic heart valves), cirrhosis, total parenteral nutrition, and ileal disease or resection. They are small, hard, and multiple. Brown pigment stones are associated with biliary infection and stasis, and unlike other stone types, can form de novo within the bile ducts. They are associated with recurrent pyogenic cholangitis, parasitic infections (Clonorchis sinensis, Opisthorchis viverrini, Ascaris lumbricoides), and biliary strictures. Brown pigment stones are soft and friable, reflecting their composition of calcium bilirubinate, fatty acid soaps, and cholesterol.
Natural History
Approximately 80% of gallstones remain asymptomatic throughout a patient's lifetime. The annual risk of developing symptoms is 1 to 4%. Biliary colic represents the initial symptomatic manifestation, characterized by episodic right upper quadrant or epigastric pain lasting more than 30 minutes, often provoked by meals containing fat, and occurring without fever or leukocytosis.
Prophylactic cholecystectomy is not recommended for asymptomatic gallstones, with specific exceptions: porcelain gallbladder (due to gallbladder cancer risk), gallstones exceeding 3 cm in diameter, gallbladder polyps measuring 10 mm or greater, and anomalous pancreaticobiliary duct junction.
Choledocholithiasis
Clinical Presentation
Choledocholithiasis, the presence of stones within the common bile duct, presents with a variable clinical picture. The classic presentation includes abdominal pain in a biliary colic pattern, jaundice, and elevated liver function tests in a cholestatic pattern with elevated alkaline phosphatase, gamma-glutamyl transferase, and direct bilirubin. Notably, transaminases may be elevated transiently to levels exceeding 1000 IU/L during acute stone impaction, which can mimic acute hepatitis before the cholestatic pattern becomes apparent. Choledocholithiasis may also be entirely asymptomatic, discovered incidentally on imaging. Approximately 10 to 15% of patients with gallbladder stones have concurrent common bile duct stones.
Diagnosis -- Risk Stratification (ASGE 2019)
The American Society for Gastrointestinal Endoscopy guidelines establish a risk stratification framework that guides the diagnostic and therapeutic approach to suspected choledocholithiasis.
High Risk (>50% probability) -- Proceed directly to ERCP
High-risk criteria include direct visualization of a common bile duct stone on imaging (ultrasound, CT, or MRI), clinical ascending cholangitis manifesting as Charcot triad, or the combination of total bilirubin exceeding 4 mg/dL with a dilated CBD on ultrasound. These patients should proceed directly to therapeutic ERCP without additional confirmatory imaging.
Intermediate Risk (10-50%) -- Perform EUS or MRCP first
Intermediate-risk criteria include abnormal liver biochemistries (elevated bilirubin, alkaline phosphatase, or ALT/AST), age greater than 55 years, or a dilated common bile duct on ultrasound (greater than 6 mm, or greater than 8 mm post-cholecystectomy) without a visualized stone. These patients require confirmatory imaging before proceeding to therapeutic intervention. Endoscopic ultrasound is the most sensitive and specific test for common bile duct stones, with sensitivity of 94 to 98% and specificity of 95 to 98%, and has the advantage of allowing same-session ERCP if a stone is confirmed. Magnetic resonance cholangiopancreatography offers sensitivity of 85 to 95% for stones exceeding 6 mm but has lower sensitivity for small stones below 6 mm. It is non-invasive but does not permit therapeutic intervention.
Low Risk (<10%) -- Proceed to cholecystectomy
When no predictors of choledocholithiasis are present, patients should proceed to cholecystectomy without preoperative ERCP or EUS. Intraoperative cholangiogram or laparoscopic common bile duct exploration may be performed if stones are suspected during surgery.
Treatment
ERCP with Sphincterotomy and Stone Extraction
Endoscopic retrograde cholangiopancreatography with biliary sphincterotomy and stone extraction is the gold standard therapeutic intervention for choledocholithiasis. Biliary sphincterotomy creates an opening in the sphincter of Oddi to facilitate stone extraction. Stones are removed using balloon sweep and/or basket extraction. The overall success rate is 85 to 95% for stones smaller than 10 mm, with lower success rates for larger stones exceeding 15 mm.
Management of Difficult Stones
Large stones exceeding 15 mm present a therapeutic challenge requiring advanced techniques. Mechanical lithotripsy uses a crushing basket to fragment stones before extraction. Papillary large balloon dilation, performed after sphincterotomy, uses a 12 to 20 mm dilation balloon to widen the papillary orifice for extraction of large stones. Cholangioscopy using the SpyGlass digital system provides direct visualization of the bile duct interior and enables electrohydraulic lithotripsy or laser lithotripsy under direct vision, which is particularly useful for stones that cannot be fragmented by mechanical means. When complete stone clearance cannot be achieved in a single session, a temporary 10 French plastic biliary stent is placed to decompress the bile duct and allow a planned second procedure.
Complications of ERCP
Post-ERCP pancreatitis is the most common complication, occurring in 3 to 15% of patients. Risk factors include sphincter of Oddi dysfunction, female sex, difficult cannulation, and pancreatic duct injection. Prevention relies on rectal indomethacin 100 mg administered at the time of the procedure combined with prophylactic placement of a 5 French pancreatic duct stent in high-risk patients. Post-sphincterotomy bleeding occurs in 1 to 2% and is usually self-limited, managed with epinephrine injection, thermal coagulation, or endoscopic clips. Perforation occurs in approximately 1%, with retroperitoneal perforations (from guidewire or sphincterotomy) typically managed conservatively. Peritoneal perforations are rare and may require surgical intervention. Post-procedure cholangitis occurs in approximately 1%, particularly when biliary drainage is incomplete. Long-term risks of sphincterotomy include recurrent common bile duct stones in 10 to 20% over 10 to 15 years.
<image>An ASGE risk stratification algorithm for choledocholithiasis. Start with "Suspected choledocholithiasis (biliary colic + cholestatic LFT elevation)." Three risk categories with criteria and management pathways. High Risk (red, >50%): "CBD stone on imaging, OR clinical cholangitis, OR bilirubin > 4 + dilated CBD" -> "Proceed directly to ERCP." Intermediate Risk (yellow, 10-50%): "Abnormal LFTs (any), OR age > 55, OR dilated CBD on US (no stone seen)" -> "EUS or MRCP first" -> if stone confirmed: "ERCP"; if no stone: "Proceed to cholecystectomy." Low Risk (green, <10%): "No predictors" -> "Cholecystectomy (with or without IOC)." Include a comparison box of EUS vs MRCP: EUS (sensitivity 94-98%, specificity 95-98%, detects small stones < 6 mm, procedural with same-session ERCP possible, requires sedation) vs MRCP (sensitivity 85-95%, specificity 90-95%, non-invasive, misses small stones, no therapeutic capability). Use the three-color risk stratification scheme with clear decision arrows.</image>
Acute Cholangitis
Pathogenesis
Acute cholangitis results from the combination of biliary obstruction and bacterial infection of the bile duct system. Choledocholithiasis is the most common cause, responsible for 28 to 70% of cases. Other causes include malignant biliary obstruction, post-ERCP complications, biliary stent occlusion, and parasitic infections. The organisms most commonly isolated are Escherichia coli (25 to 50%), Klebsiella species (15 to 20%), Enterococcus species (10 to 20%), Pseudomonas species, and anaerobes including Bacteroides and Clostridium. Normal bile is sterile; obstruction promotes bacterial colonization through translocation from the gut and stasis of bile.
Clinical Presentation
The Charcot triad of fever with chills, jaundice, and right upper quadrant pain is present in 50 to 70% of patients with acute cholangitis. The Reynolds pentad adds hypotension and altered mental status to the Charcot triad and indicates severe suppurative cholangitis; this full pentad is present in only 5 to 10% of cases but portends a markedly worse prognosis. Laboratory findings include leukocytosis, elevated bilirubin (often exceeding 4 to 5 mg/dL), elevated alkaline phosphatase and gamma-glutamyl transferase, and elevated AST and ALT (which may transiently exceed 1000 IU/L). Blood cultures are positive in 40 to 70% of cases, underscoring the importance of obtaining cultures before antibiotic initiation.
Tokyo Guidelines (TG18) Severity Grading
| Grade | Severity | Criteria | Management |
|---|---|---|---|
| I | Mild | Does not meet Grade II or III criteria; responds to initial medical therapy | Antibiotics + elective ERCP within 24-48 hours |
| II | Moderate | WBC >12K or <4K, fever ≥39°C, age ≥75, bilirubin ≥5 mg/dL, or albumin <0.7× LLN | Antibiotics + ERCP within 24 hours |
| III | Severe | Organ dysfunction: cardiovascular (vasopressors), neurologic (altered consciousness), respiratory (P/F <300), renal (Cr >2), hepatic (INR >1.5), or hematologic (Plt <100K) | Antibiotics + urgent ERCP within 12 hours; ICU care |
The Tokyo Guidelines provide a standardized severity grading system for acute cholangitis. Grade I (mild) cholangitis does not meet criteria for moderate or severe disease and responds to initial medical therapy. Grade II (moderate) is characterized by any of the following: white blood cell count exceeding 12,000 or below 4,000, fever of 39 degrees Celsius or greater, age 75 years or greater, bilirubin 5 mg/dL or greater, or albumin below 0.7 times the lower limit of normal. Grade III (severe) is defined by the presence of organ dysfunction in any system: cardiovascular (hypotension requiring vasopressors), neurologic (altered consciousness), respiratory (PaO2/FiO2 ratio below 300), renal (oliguria or creatinine exceeding 2 mg/dL), hepatic (INR exceeding 1.5), or hematologic (platelets below 100,000).
Management
Medical
Intravenous antibiotics should be initiated immediately after blood cultures are obtained. For mild to moderate cholangitis, appropriate regimens include piperacillin-tazobactam 4.5 grams every 8 hours, ciprofloxacin 400 mg every 12 hours plus metronidazole 500 mg every 8 hours, or ceftriaxone 1 to 2 grams daily plus metronidazole. For severe cholangitis, broader coverage with meropenem 1 gram every 8 hours or imipenem 500 mg every 6 hours is appropriate, particularly when nosocomial or resistant organisms are suspected. Antibiotic duration is typically 4 to 7 days after source control is achieved, and may be shortened to as few as 3 days when rapid source control is obtained. Intravenous fluid resuscitation and vasopressor support are provided as clinically indicated.
Biliary Drainage (Source Control)
ERCP is the first-line approach to biliary drainage and source control. For mild to moderate cholangitis, ERCP should be performed within 24 to 48 hours. For severe (grade III) cholangitis with organ dysfunction, urgent ERCP is indicated within 12 hours, as delay increases mortality. When complete stone extraction is technically feasible and safe, sphincterotomy with stone extraction should be performed. When complete extraction is not safe or achievable, nasobiliary drainage or placement of a plastic biliary stent provides biliary decompression, with definitive stone extraction deferred to a second procedure.
Percutaneous transhepatic biliary drainage is the alternative when ERCP fails or when anatomy precludes the endoscopic approach, such as in patients with altered surgical anatomy or duodenal obstruction. EUS-guided biliary drainage is an emerging alternative to percutaneous drainage when ERCP fails, using techniques such as choledochoduodenostomy or hepaticogastrostomy with lumen-apposing metal stents, though these procedures require specialized expertise. Surgical common bile duct exploration is reserved as a last resort, as it carries the highest morbidity in the acute setting.
Sphincter of Oddi Dysfunction (SOD)
Reclassification (Rome IV / Post-EPISOD Era)
The understanding and classification of sphincter of Oddi dysfunction has undergone significant revision in recent years. Functional biliary sphincter disorder describes recurrent biliary-type pain in post-cholecystectomy patients with objective evidence of biliary obstruction.
Type I, previously termed SOD type I, presents with biliary-type pain accompanied by a dilated common bile duct exceeding 12 mm and elevated liver function tests during pain episodes. This likely represents structural sphincter stenosis, and sphincterotomy is beneficial without the need for manometry. Type II presents with pain plus one objective finding (either a dilated CBD or elevated LFTs), with equivocal benefit from sphincterotomy.
Type III, the most important reclassification, presents with biliary-type pain alone without any objective findings. The landmark EPISOD trial demonstrated no benefit of sphincterotomy over sham procedure in this group. Accordingly, manometry and sphincterotomy should not be performed, and these patients should be treated as functional pain using neuromodulatory and behavioral approaches.
Sphincter of Oddi manometry, when indicated for type I or II with equivocal findings, uses an aspiration catheter or water-perfused catheter to measure basal sphincter pressure. A pressure exceeding 40 mmHg is considered elevated. The procedure is associated with a 20 to 30% risk of post-ERCP pancreatitis, the highest of any ERCP indication.
Gallbladder Polyps
Management
The management of gallbladder polyps follows a size-based algorithm incorporating malignancy risk factors. Polyps smaller than 6 mm require no follow-up in the absence of risk factors such as primary sclerosing cholangitis or Indian ethnicity. Polyps measuring 6 to 9 mm warrant ultrasound follow-up at 6 months and then annually for 2 years, with cholecystectomy recommended if growth is demonstrated. Polyps measuring 10 mm or greater require cholecystectomy, as the malignancy risk is 10 to 25%.
Polyps occurring in conjunction with gallstones warrant cholecystectomy regardless of polyp size, as the synergistic cancer risk is increased. Risk factors for malignancy in gallbladder polyps include size exceeding 10 mm, a solitary polyp, sessile morphology, age over 50, primary sclerosing cholangitis, and Indian ethnicity.
Mirizzi Syndrome
Mirizzi syndrome results from external compression of the common hepatic duct by a gallstone impacted in the cystic duct or Hartmann pouch. The classification system defines type I as extrinsic compression without fistula formation, and types II through V as progressively more extensive cholecystocholedochal fistulae with increasing involvement of the common bile duct wall.
Diagnosis is established by MRCP or EUS, with CT potentially demonstrating the compression pattern. Treatment requires cholecystectomy, which is often converted from laparoscopic to open due to the dense inflammatory changes. Common bile duct reconstruction may be necessary in higher-grade fistulae. Preoperative ERCP with stent placement for biliary decompression is frequently performed.
<image>An endoscopic image panel showing key biliary procedures during ERCP. Four panels: Panel 1 "Cholangiography": fluoroscopic image showing contrast-filled biliary tree with a filling defect (stone) in the distal CBD, labeled CBD, CHD, right and left hepatic ducts, and cystic duct stump. Panel 2 "Biliary sphincterotomy": endoscopic view of the major duodenal papilla with the sphincterotome wire cutting through the sphincter using electrocautery, showing the incision direction (11 o'clock) and exposed bile duct lumen. Panel 3 "Balloon extraction": extraction balloon inflated in the CBD above a stone, being swept downward through the sphincterotomy to extract the stone, with the stone visible at the papillary orifice. Panel 4 "Cholangioscopy (SpyGlass)": direct visualization of the bile duct interior through a digital cholangioscope showing a large brown pigment stone impacted in the duct, with the fiber-optic view showing the stone surface texture and surrounding duct wall. Include labels for all endoscopic landmarks (papilla, pancreatic duct orifice, bile duct orifice, ampulla). Use realistic endoscopic coloring with duodenal mucosa in pink-tan, bile duct in yellow, and stone in dark brown/green.</image>
Choledochal Cysts
Todani Classification
| Todani Type | Frequency | Description | CCA Risk | Treatment |
|---|---|---|---|---|
| I | 80-90% | Fusiform CBD dilation | High (10-30% lifetime) | Complete excision + hepaticojejunostomy |
| II | 2% | True diverticulum of CBD | Moderate | Excision + hepaticojejunostomy |
| III (Choledochocele) | 1-5% | Intraduodenal distal CBD dilation | Low | Sphincterotomy may suffice |
| IVa | 15-35% | Intra- and extrahepatic dilation | High | Complete excision + hepaticojejunostomy |
| IVb | Rare | Extrahepatic dilation only | Moderate | Excision |
| V (Caroli disease) | Rare | Intrahepatic bile duct cystic dilation | Variable | Liver transplant for recurrent complications |
Choledochal cysts are congenital dilations of the biliary tree classified according to the Todani system. Type I cysts, representing 80 to 90% of cases, consist of fusiform dilation of the common bile duct and are the most commonly encountered. Type II cysts (2%) are true diverticula arising from the common bile duct wall. Type III cysts (choledochoceles, 1 to 5%) represent intraduodenal dilation of the distal common bile duct. Type IV cysts (15 to 35%) are subdivided into type IVa (intrahepatic and extrahepatic dilation) and type IVb (extrahepatic dilation only). Type V cysts, known as Caroli disease, involve cystic dilation of the intrahepatic bile ducts and are associated with congenital hepatic fibrosis and autosomal recessive polycystic kidney disease.
The lifetime risk of cholangiocarcinoma in choledochal cysts is 10 to 30%, with types I and IV carrying the highest risk. Treatment is complete excision with hepaticojejunostomy for types I, II, and IV. Sphincterotomy may suffice for type III (choledochocele). Type V (Caroli disease) with recurrent complications may ultimately require liver transplantation.
Key Clinical Pearls
- ASGE risk stratification guides the choledocholithiasis workup: high risk leads directly to ERCP, intermediate risk requires EUS or MRCP first, and low risk proceeds to cholecystectomy.
- Rectal indomethacin 100 mg plus prophylactic pancreatic duct stent placement are the standard for post-ERCP pancreatitis prevention in high-risk patients.
- Tokyo Guidelines Grade III cholangitis (organ dysfunction) requires urgent biliary drainage within 12 hours. Delay increases mortality.
- SOD Type III (pain only, no objective findings): the EPISOD trial showed no benefit of sphincterotomy. These patients should be treated as functional pain, and manometry and ERCP should not be performed.
- Gallbladder polyps measuring 10 mm or greater require cholecystectomy due to a 10 to 25% malignancy risk.
- EUS is the most sensitive test for small CBD stones (below 6 mm), superior to MRCP for detecting small stones.
- Choledochal cysts carry a 10 to 30% lifetime cholangiocarcinoma risk. Complete excision is the treatment of choice.
- Large CBD stones (exceeding 15 mm) often require advanced techniques: cholangioscopy-guided lithotripsy, papillary large balloon dilation, or mechanical lithotripsy.
References
- ASGE Standards of Practice Committee. The role of endoscopy in the evaluation of suspected choledocholithiasis. Gastrointest Endosc. 2019;89(6):1075-1105.
- Miura F, et al. TG18 flowchart for the management of acute cholangitis and cholecystitis (Tokyo Guidelines 2018). J Hepatobiliary Pancreat Sci. 2018;25(1):31-40.
- Cotton PB, et al. Effect of endoscopic sphincterotomy for suspected sphincter of Oddi dysfunction on pain-related disability following cholecystectomy (EPISOD). JAMA. 2014;311(20):2101-2109.
- Buxbaum JL, et al. ASGE guideline on the role of endoscopy in the evaluation and management of choledocholithiasis. Gastrointest Endosc. 2019;89(6):1075-1105.
- Manes G, et al. Prophylaxis of post-ERCP pancreatitis. Endoscopy. 2017;49(03):303-311.
