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Choledocholithiasis


BASICS


DESCRIPTION


  • 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 bactibilia
    • Secondary stones (more common) form within the gallbladder
      • Migrate 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 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)
  • 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/dL
      • Presence 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 choledocholithiasis
    • Transabdominal 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 cost
    • 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
    • Cholescintigraphy (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 diagnosis
    • Percutaneous 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 stone
    • T-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 IV
      • Ciprofloxacin 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 mm
      • Stones associated with complicated biliary strictures (PSC, hepatolithiasis)
      • Surgically altered anatomy (Roux-en-Y gastric bypass, Billroth II gastrojejunostomy)
      • Mirizzi syndrome
    • Consider 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.
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