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Choledocholithiasis

BASICS

DESCRIPTION

- Asymptomatic (30-50%) - Right upper quadrant (RUQ) pain: - Moderate/intense spasmodic pain, often intermittent, transient, recurrent (biliary colic) - May radiate to right shoulder/back, not relieved by antacids - Occurs after meals, especially fatty, greasy foods

- Secondary effects of obstruction: - Nausea/vomiting - Jaundice/pruritus - Clay-colored stool - Tea-colored urine - Pancreatitis (pain radiating to back)

- Magnetic resonance cholangiopancreatography (MRCP): - Sensitivity 93%, specificity 96% (may miss stones <5 mm) (2)[A],(3) - Most accurate noninvasive test; no contrast required - Preferred over endoscopic retrograde cholangiopancreatography (ERCP), when the probability of choledocholithiasis is intermediate (only one strong predictor) - No associated morbidity and may be less costly than diagnostic ERCP

  • Stones in common bile duct (CBD)
  • Several types: cholesterol (majority), calcium bilirubinate or pigment, and mixed stones
  • System(s) affected: gastrointestinal; hepatobiliary
  • Synonym(s): CBD stones; CBD calculi

EPIDEMIOLOGY

Incidence

  • Gallstones affect more than 20 million in United States.Choledocholithiasis is noted in 7-12% of patients undergoing cholecystectomy for symptomatic gallstones (1) and 18-33% of patients with acute biliary pancreatitis (2).
  • Increases with age (30-50% of patients >60 years with gallstones have choledocholithiasis)
  • Incidence of gallstones in U.S. adults is 10-20%, rising to 40% in patients over 60 years old.
  • Internationally, parasitic infections (e.g., Ascaris lumbricoides) contribute to incidence.

Prevalence

  • Gallstone disease in general population = 6-15% (3)
  • Predominant sex: female > male

ETIOLOGY AND PATHOPHYSIOLOGY

  • CBD stones may be primary or secondary.Primary stones form within the biliary tract due to any condition leading to bile stasis or chronic bactibiliaSecondary stones (more common) form within the gallbladderMigrate from the gallbladder to the biliary tree.
  • Chronic hemolytic states increase gallstone risk.
  • Formation of de novo pigment stones can result from:Dilated, sclerosed, or strictured ducts (e.g., recurrent cholangitis)Hepatobiliary parasitism

Genetics

  • MDR3 defects may predispose to biliary sludge, cholelithiasis, cholestasis of pregnancy, and subsequent choledocholithiasis.
  • Increased prevalence in Hispanics
  • Hepatobiliary cholesterol hemitransporter ABCG8 variant p.D19H doubles the odds of gallstone recurrence after cholecystectomy (4)[B].

RISK FACTORS

  • Cholelithiasis
  • Pancreatitis (30%)
  • Obesity
  • High consumption of long-chain saturated fatty acids
  • Chronic hemolysis
  • Chronic estrogen exposure
  • Rapid weight loss (>25% of original weight, especially after bariatric surgery)
  • Prior cholecystectomy:<2 years prior: considered a "retained" stone>2 years prior: considered "recurrent" stone

GENERAL PREVENTION

Maintain healthy weight and lifestyle. Avoid rapid loss of excess weight.

COMMONLY ASSOCIATED CONDITIONS

  • Cholelithiasis, cholecystitis, cholangitis
  • Gallstone pancreatitis

DIAGNOSIS

HISTORY

  • Asymptomatic (30-50%)
  • Right upper quadrant (RUQ) pain:Moderate/intense spasmodic pain, often intermittent, transient, recurrent (biliary colic)May radiate to right shoulder/back, not relieved by antacidsOccurs after meals, especially fatty, greasy foods
  • Secondary effects of obstruction:Nausea/vomitingJaundice/pruritusClay-colored stoolTea-colored urinePancreatitis (pain radiating to back)
  • Assess for infection (may progress to cholangitis and septic shock):Fever, chills, orthostasis, signs of inadequate organ perfusion
  • History of CBD strictures, recurrent sclerosing cholangitis, sphincter of Oddi dysfunction, cholelithiasis
  • History of rapid loss of >25% of excess weight after gastric bypass

PHYSICAL EXAM

  • Fever, hypotension, tachycardia
  • Moderate RUQ tenderness on palpation (Murphy sign); palpable gallbladder (less common)
  • Jaundice
  • Fever, RUQ pain, and jaundice (Charcot triad) + shock and altered mental status (Reynolds pentad) suggest cholangitis.
  • Rebound tenderness or guarding often absent

DIFFERENTIAL DIAGNOSIS

Cholangitis (acute or primary sclerosing), cholangiocarcinoma, sphincter of Oddi dysfunction, biliary parasites, papillary stenosis, biliary stricture, narrowed biliary-enteric anastomosis

DIAGNOSTIC TESTS & INTERPRETATION

Initial Tests (lab, imaging)

  • Labs:Liver function tests often show obstructive pattern, elevated total bilirubin, alkaline phosphatase, gamma-glutamyl-transpeptidase (5)Alkaline phosphatase >125 IU/L-92% sensitivity, 79% specificity (5)Normal liver tests have high negative predictive value (2)[A].Probability of choledocholithiasis is high (>50%) if (2)[A]:Presence of: gallstones on ultrasound, clinical signs of ascending cholangitis, or total bilirubin >4 mg/dLPresence of both dilated CBD (>6 mm with gallbladder in situ) and total bilirubin between 1.8 and 4 mg/dL
  • Imaging: most effective to confirm choledocholithiasisTransabdominal ultrasound (US):Can detect CBD dilatation (sensitivity 77-87%) (2)[A]; less reliable for detecting CBD stones (sensitivity 73%, specificity 91%) (5)NPV of normal CBD = 95-96% (4)Endoscopic US:Sensitivity 95% and specificity 97% (3). Highly sensitive even for smaller stones (2)More invasive; higher costMagnetic resonance cholangiopancreatography (MRCP):Sensitivity 93%, specificity 96% (may miss stones <5 mm) (2)[A],(3)Most accurate noninvasive test; no contrast requiredPreferred over endoscopic retrograde cholangiopancreatography (ERCP), when the probability of choledocholithiasis is intermediate (only one strong predictor)No associated morbidity and may be less costly than diagnostic ERCPCholescintigraphy (HIDA/DISIDA scan): Isotope derivatives taken up by hepatocytes and excreted into biliary tree. Assesses bile duct obstruction, cystic duct obstruction, or bile leakage:May be combined with CCK to observe GB function and estimate GB ejection fraction

Diagnostic Procedures/Other

  • Cholangiography is the gold standard for determining the presence of CBD stones:ERCP (sensitivity 83%, specificity 99%) (6): allows for papillotomy/stone extraction at time of diagnosisPercutaneous transhepatic cholangiography (PTC): Needle puncture of hepatic duct with injection of radiopaque dye. Used in patients with extensive bile duct stone disease or in whom ERCP would be difficult.Intraoperative cholangiography (IOC): Contrast in cystic duct during cholecystectomy. Ongoing debate if should be routine during cholecystectomy. Sensitivity 99%, specificity 99% (6)
  • Endoscopic ultrasound (EUS): more likely to detect stones than transabdominal ultrasound (TUS):EUS or MRCP use can avoid ERCP in up to 67%.
  • Intraoperative intraluminal ultrasonography:Can be performed during laparoscopic or open procedures. Sensitivity of 71-100% (2)[A]Helpful in patients with contrast dye allergy
  • Postoperative studies:MRI (MRCP) to diagnose CBD stoneT-tube cholangiography
  • Choledochoscopy can be used to extract stones intraoperatively or via t-tube tract.

TREATMENT

Goal is to relieve obstruction. If not symptomatic, small stones may pass spontaneously.

MEDICATION

Antibiotics to cover enteric flora if infection is suspected

First Line

  • Broad-spectrum antibiotics (substitute fluoroquinolones for penicillin-allergic patients)
  • In absence of cholangitis, routine antibiotic prophylaxis prior to endoscopic procedure is not indicated, unless incomplete drainage is anticipated (e.g., PSC, hilar strictures).
  • Antibiotics:Piperacillin-tazobactam (Zosyn): 3.375 g IV q6h (7,8)[A]Fluoroquinolones have good biliary penetration:Levofloxacin 750 mg/day IVCiprofloxacin 400 mg IV BID (8)[A]
  • Duration of therapy depends on rapidity of response, bacteremia, and subsequent need for surgery to correct biliary obstruction.
  • Add metronidazole for anaerobic coverage in patients with sepsis, elderly patients, and patients with previous biliary manipulation (may not be necessary with newer broad-spectrum penicillins):Metronidazole 500 mg IV q8h (7,8)[A]

SURGERY/OTHER PROCEDURES

  • ERCP with stone extraction is first-line management.Generally involves enlarging the papillary orifice, either by dividing sphincterotomy or papillary balloon dilation (1).High success rate (>98%) (7)Low complication rate (mortality 0.5%, pancreatitis 1.3-6.7%, perforation 0.1-1.1%, bleeding from sphincterotomy 0.3-2.0%, cholangitis 1%) (2)[A]Long-term biliary stenting is an acceptable alternative in frail patients with stones that are not endoscopically retrievable (1,7)[A] .Clinical situations with complicated biliary stone disease include (9)[A]:Stones >15 mmStones associated with complicated biliary strictures (PSC, hepatolithiasis)Surgically altered anatomy (Roux-en-Y gastric bypass, Billroth II gastrojejunostomy)Mirizzi syndromeConsider transfer to a large volume, tertiary center to manage complicated biliary stone disease.If biliary stone is >10 mm, endoscopic sphincterotomy with endoscopic papillary balloon dilation, mechanical lithotripsy, electrohydraulic lithotripsy, or laser lithotripsy are possible options during ERCP (9)[A].
  • Surgical CBD stone removal has a high success rate (75-95%) with few complications:Laparoscopic cholecystectomy with CBD exploration is as safe and efficient as ERCP (10)[A].First-stage management of symptomatic CBD stones with laparoscopic cholecystectomy + laparoscopic CBD exploration and second-stage management utilizing ERCP/EST (endoscopic sphincterotomy) + laparoscopic cholecystectomy, have similar stone clearance, similar morbidity, mortality, and length of hospital stay (10,11)[A].Consider a CBD lumen catheter if laparoscopic CBD exploration is not feasible and the chance of a CBD stone is <65%.Open choledochotomy is reserved for complex cases when laparoscopic and endoscopic techniques fail (unless patient is already undergoing an open procedure).
  • Surgical drainage via external catheter or by papillotomy through ampulla of Vater
  • Indications for drainage: sphincter of Oddi sclerosis or dysfunction, multiple or primary CBD stones, or previous stone

Admission Criteria/Initial Stabilization

  • To control serious infection and urgently decompress CBD
  • NPO, antibiotics, and IV hydration if infection suspected

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

After endoscopic bile duct clearance, patients should undergo cholecystectomy within 1 week (4)[A].

Patient Monitoring

  • Serial liver function tests and bilirubin levels, WBC, and pancreatic enzymes as clinically indicated (2)[A]
  • Patients with weight loss >25% from original weight after bariatric surgery may benefit from US surveillance and cholecystectomy if gallstones are identified (12)[A].

PROGNOSIS

  • With treatment, prognosis is good.
  • Untreated, 55% of patients will have complications.

COMPLICATIONS

  • Cholangitis: most frequent (60%)
  • Retained CBD stones (2-10%)
  • Pancreatitis
  • Pancreatitis following ERCP (incidence rate 1.3-6.7%)
  • Biliary enteric fistula, hemobilia, bile duct injury, hepatic dysfunction/failure (rare)

REFERENCES

11 Trikudanathan G, Arain M, Attam R, et al. Advances in the endoscopic management of common bile duct stones. Nat Rev Gastroenterol Hepatol. 2014;11(9):535-544.22 Maple JT, Ben-Menachem T, Anderson MA, et al. The role of endoscopy in the evaluation of suspected choledocholithiasis. Gastrointest Endosc. 2010;71(1):1-9.33 Giljaca V, Gurusamy KS, Takwoingi Y, et al. Endoscopic ultrasound versus magnetic resonance cholangiopancreatography for common bile duct stones. Cochrane Database Syst Rev. 2015;(2):CD011549.44 Krawczyk M, Stokes CS, Lammert F. Genetics and treatment of bile duct stones: new approaches. Curr Opin Gastroenterol. 2013;29(3):329-335.55 Gurusamy KS, Giljaca V, Takwoingi Y, et al. Ultrasound versus liver function tests for diagnosis of common bile duct stones. Cochrane Database Syst Rev. 2015;(2):CD011548.66 Gurusamy KS, Giljaca V, Takwoingi Y, et al. Endoscopic retrograde cholangiopancreatography versus intraoperative cholangiography for diagnosis of common bile duct stones. Cochrane Database Syst Rev. 2015;(2):CD010339.77 Kochar R, Banerjee S. Infections of the biliary tract. Gastrointest Endosc Clin N Am. 2013;23(2):199-218.88 Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clin Infect Dis. 2010;50(2):133-164.99 Maple JT, Ikenberry SO, Anderson MA, et al. The role of endoscopy in the management of choledocholithiasis. Gastrointest Endosc. 2011;74(4):731-744.1010 Dasari BV, Tan CJ, Gurusamy KS, et al. Surgical versus endoscopic treatment of bile duct stones. Cochrane Database Syst Rev. 2013;(12):CD003327.1111 Lu J, Cheng Y, Xiong XZ, et al. Two-stage vs single-stage management for concomitant gallstones and common bile duct stones. World J Gastroenterol. 2012;18(24):3156-3166.1212 Li VK, Pulido N, Fajnwaks P, et al. Predictors of gallstone formation after bariatric surgery: a multivariate analysis of risk factors comparing gastric bypass, gastric banding, and sleeve gastrectomy. Surg Endosc. 2009;23(7):1640-1644.

ADDITIONAL READING

  • Abdelmajid K, Houssem H, Rafik G, et al. Open choldecho-enterostomy for common bile duct stones: is it out of date in laparo-endoscopic era? N Am J Med Sci. 2013;5(4):288-292.
  • Alexakis N, Connor S. Meta-analysis of one- vs. two-stage laparoscopic/endoscopic management of common bile duct stones. HPB (Oxford). 2012;14(4):254-259.
  • De Palma GD. Minimally invasive treatment of cholecysto-choledocal lithiasis: the point of view of the surgical endoscopist. World J Gastrointest Surg. 2013;5(6):161-166.
  • Kharbutli B, Velanovich V. Management of preoperatively suspected choledocholithiasis: a decision analysis. J Gastrointest Surg. 2008;12(11):1973-1980.
  • Rogers SJ, Cello JP, Horn JK, et al. Prospective randomized trial of LC+LCBDE vs ERCP/S+LC for common bile duct stone disease. Arch Surg. 2010;145(1):28-33.
  • Trivedi PJ, Tse D, Al-Bakir I, et al. Appropriate patient selection in the management of common bile duct stones: when not to do ERCP. ISRN Surg. 2012;2012:286365.

SEE ALSO

Cholangitis, Acute; Cholecystitis; Cholelithiasis; Jaundice

CODES

ICD10

  • K80.50 Calculus of bile duct w/o cholangitis or cholecyst w/o obst
  • K80.51 Calculus of bile duct w/o cholangitis or cholecyst w obst
  • K80.40 Calculus of bile duct w cholecystitis, unsp, w/o obstruction
  • K80.41 Calculus of bile duct w cholecystitis, unsp, w obstruction
  • K80.42 Calculus of bile duct w acute cholecystitis w/o obstruction
  • K80.47 Calculus of bile duct w acute and chronic cholecyst w obst
  • K80.46 Calculus of bile duct w acute and chronic cholecyst w/o obst
  • K80.45 Calculus of bile duct w chronic cholecystitis w obstruction
  • K80.43 Calculus of bile duct w acute cholecystitis with obstruction
  • K80.44 Calculus of bile duct w chronic cholecyst w/o obstruction

ICD9

  • 574.50 Calculus of bile duct without mention of cholecystitis, without mention of obstruction
  • 574.51 Calculus of bile duct without mention of cholecystitis, with obstruction
  • 574.30 Calculus of bile duct with acute cholecystitis, without mention of obstruction
  • 574.31 Calculus of bile duct with acute cholecystitis, with obstruction
  • 574.40 Calculus of bile duct with other cholecystitis, without mention of obstruction
  • 574.41 Calculus of bile duct with other cholecystitis, with obstruction

SNOMED

  • Common bile duct calculus (disorder)
  • Calculus of common bile duct with acute cholecystitis
  • Calculus of common bile duct with chronic cholecystitis
  • Calculus of common bile duct with chronic cholecystitis without obstruction
  • Calculus of common bile duct with acute cholecystitis without obstruction
  • Calculus of common bile duct with acute cholecystitis with obstruction
  • Calculus of common bile duct with chronic cholecystitis with obstruction

CLINICAL PEARLS

  • Stones in the CBD are either primary (arising within the duct) or secondary (migrate into the duct from the gallbladder).
  • Cholangiography is "gold standard" for diagnosis.
  • MRCP is the most accurate noninvasive test.
  • ERCP can be used in diagnosis and therapy.
  • Cholangitis is most frequent complication.
  • TUS is more useful for detecting CBD dilation (finding associated with choledocholithiasis) than detecting CBD stones.