- Cholelithiasis manifests in cholesterol, pigment, or mixed stones formed and contained in the gallbladder.
- Synonym(s): Gallstones
- Uncommon at <10 years
- Most gallstones in the pediatric population are pigment stones associated with blood dyscrasia.
- Increased in Native Americans and Hispanics
- Increases with age by 1–3% per year; peaks at 7th decade; 2% of the US population develops gallstones annually.
- Population: 8–10% of the US
- Predominant sex: Female > Male (2–3:1)
Etiology and Pathophysiology
Gallstone formation is a complex process mediated by genetic, metabolic, immune, and environmental factors. Gallbladder sludge (a mixture of cholesterol crystals, calcium bilirubinate granules, and mucin gel matrix) serves as the nidus for gallstone formation.
- Production of bile supersaturated with cholesterol (cholesterol stones)
- Decrease in bile content of either phospholipid (lecithin) or bile salts
- Biliary stasis or impaired gallbladder motility
- Generation of excess unconjugated bilirubin in patients with hemolytic diseases; passage of excess bile salt into the colon with subsequent absorption of excess unconjugated bilirubin in patients with inflammatory bowel disease (IBD) or after distal ileal resection (black or pigment stones)
- Hydrolysis of conjugated bilirubin or phospholipid by bacteria in patients with biliary tract infection or stricture (brown stones or primary bile duct stones; rare in the Western world and common in Asia)
- Age (peak in 60–70s)
- Female gender, pregnancy, and multiparity
- Caucasian, Hispanic, or Native American descent
- High-fat diet rich in cholesterol
- Cholestasis or impaired gallbladder motility in association with prolonged fasting, long-term total parenteral nutrition, and rapid weight loss
- Hereditary (e.g., patients carrying the p.D19H variant for the hepatocanalicular cholesterol transporter ABCG5/ABG8 have an increased risk for gallstones)
- Metabolic syndrome (i.e., obesity, dyslipidemia, and type 2 diabetes) and metabolic changes in association with short gut syndrome, terminal ileal resection, and IBD
- Hemolytic disorders (e.g., hereditary spherocytosis and sickle cell anemia) and cirrhosis (for black or pigment stones)
- Medications (e.g., early use of birth control pills, estrogen replacement therapy at high doses, and long-term corticosteroid or cytostatic therapy)
- Viral hepatitis, biliary tract infection and stricture (for intraductal formation of brown pigment stones)
Commonly Associated Conditions
90% of people with gallbladder carcinoma have gallstones.
- Mostly asymptomatic (80%): 5–10% become symptomatic each year. Over their lifetime, <1/2 of patients with gallstones develop symptoms.
- Episodic right upper quadrant or epigastric pain lasting >15 minutes and sometimes radiating to the back (biliary colic), usually postprandially; most patients will develop recurrent symptoms after the first episode.
- Nausea, vomiting; indigestion or bloating sensation; fatty food intolerance
- Physical exam is usually normal in patients with cholelithiasis without acute attack.
- Epigastric and/or right upper quadrant tenderness (Murphy sign) when in association with cholecystitis
- Fever and jaundice in patients with choledocholithiasis and cholangitis; jaundice can also be caused by extrinsic compression of the bile duct by a stone in the gallbladder or cystic duct (Mirizzi syndrome)
- Flank and periumbilical ecchymoses (Cullen sign and Grey-Turner sign) in patients with acute hemorrhagic pancreatitis
- In patients with concomitant acute calculus cholecystitis and gallbladder cancer, a mass in the right upper quadrant may be palpated.
- Peptic ulcer diseases and gastritis
- Gallbladder cancer
- Gallbladder polyps
- Acalculous cholecystitis
- Biliary dyskinesia
Diagnostic Tests and Interpretation
No lab study is specific for cholelithiasis.
Initial Tests (lab, imaging)
- Leukocytosis and elevated C-reactive protein level are associated with acute calculus cholecystitis.
- US (best technique to diagnose gallstones and differentiate from cholecystitis) can detect gallstones in 97–98% of patients.
- Thickening of the gallbladder wall (≥5 mm), pericholecystic fluid, and direct tenderness when the probe is pushed against the gallbladder (sonographic Murphy sign) are all radiographic signs of acute calculus cholecystitis.
Follow-Up Tests & Special Considerations
- CT scan (no advantage over US except in detecting distal common bile duct stones)
- MR cholangiopancreatography is reserved for cases of suspected common bile duct stones due to high cost.
- Endoscopic US has been shown to be as sensitive as endoscopic retrograde cholangiopancreatography (ERCP) for detection of common bile duct stones in patients with gallstone pancreatitis.
- Hepatobiliary iminodiacetic acid (HIDA) scan is useful in differentiating acalculous cholecystitis from other causes of abdominal pain. False–positive results can arise from fasting status, insufficient resistance of the sphincter of Oddi, and gallbladder agenesis:
- Cholecystokinin (CCK)-HIDA is specifically used to diagnose gallbladder dysmotility disorder (i.e., biliary dyskinesia).
- 10–30% of gallstones, which are radiopaque calcium or pigment-containing gallstones, are more likely to be visible on plain x-ray. A “porcelain gallbladder” is a calcified gallbladder, visible by x-ray; associated with gallbladder cancer.
- Pure cholesterol stones have a white or slightly yellow color.
- Pigment stones may be black or brown. Black stones contain polymerized calcium bilirubinate, most often secondary to cirrhosis or hemolysis; these almost always form in the gallbladder.
- Brown stones are associated with biliary tract infection, caused by bile stasis, and as such may form either in the bile ducts or gallbladder.
- Treat only symptomatic gallstones and observe asymptomatic stones.
- Attempt conservative therapy during pregnancy. If necessary, perform surgery preferentially in the 2nd trimester.
- Prophylactic cholecystectomy for patients with calcified (porcelain) gallbladder (risk for gallbladder cancer), patients with sickle cell disease, and patients with recurrent pancreatitis due to microlithiasis
- In morbidly obese patients, simultaneous cholecystectomy may be performed in combination with bariatric procedures (2) in an effort to reduce later stone-related complications.
Age alone should not alter the therapy plan.
Medication (Drugs)First Line
- Analgesics for pain relief:
- Antibiotics are indicated in patients with signs of acute cholecystitis.
- Prophylactic antibiotics in low-risk patients do not prevent infections for laparoscopic cholecystectomies (4)[A].
Issues for Referral
Patients with retained or recurrent bile duct stones following cholecystectomy should be referred to gastroenterology for ERCP.
- Surgical intervention should be considered for patients who have symptomatic cholelithiasis or gallstone-related complications, such as cholecystitis, or in asymptomatic patients with immune suppression, calcified gallbladder, or family history of gallbladder cancer (5)[A].
- Open, small incision, or laparoscopic cholecystectomy (LC) has similar mortality and complication rates (6)[A]. The minimally invasive techniques offer quicker recovery. In well-selected patients, single-incision LC (SILC) and robotic LC are novel methods for the treatment of symptomatic cholelithiasis. Natural orifice transluminal endoscopic surgery (NOTES) is still at an experimental stage, and NOTES cholecystectomy is only available in a limited number of specialized centers:
- Surgery-related complications include common bile duct injury (0.5%), right hepatic duct/artery injury, retained stones, cystic duct or duct of Luschka leak, biloma formation, or bile duct stricture in the long term.
- Conversion to open procedure based on judgment of the operating surgeon
- In 10–15% patients with symptomatic cholelithiasis, common bile duct (CBD) stones are detected during LC with intraoperative cholangiogram (IOC). CBD stone(s) can be removed via either laparoscopic CBD exploration or postoperative ERCP, depending on surgeon expertise and GI availability.
- IOC may help delineate bile duct anatomy when dissection proves difficult. Selective or routine use of IOC is a topic of debate, but may be associated with earlier recognition and decreased incidence of bile duct injury (7)[B].
- Percutaneous cholecystostomy (PC) used in high-risk patients with cholecystitis or gallbladder empyema. PC may also be used in patients with symptoms of cholecystitis for >72 hours in which altered anatomy might significantly increase the surgical risk. Interval cholecystectomy is usually advisable after the resolution of cholecystitis and optimization of associated medical conditions to prevent recurrent cholecystitis.
For patients with symptomatic cholelithiasis, laparoscopic cholecystectomy has become an outpatient procedure; for patients who developed gallstone-related complications (i.e., cholecystitis, cholangitis, and pancreatitis), inpatient care is necessary.
Admission Criteria/Initial Stabilization
- Acute phase: NPO, IV fluids, and antibiotics
- Adequate pain control with narcotics and/or NSAIDs
Follow-Up RecommendationsPatient Monitoring
- Medical attention if asymptomatic stones become symptomatic
- Patients on oral dissolution agents should be followed up with liver enzyme, serum cholesterol, and imaging studies.
A low-fat diet may be helpful.
- Change in lifestyle (e.g., regular exercise) and dietary modification (low-fat diet and reduction of total calorie intake) may reduce gallstone-related hospitalizations.
- Patients with asymptomatic gallstones should be educated about the typical symptoms of biliary colic and gallstone-related complications.
- <1/2 of patients with gallstones become symptomatic.
- Cholecystectomy: Mortality <0.5% elective, 3–5% emergency; morbidity <10% elective, 30–40% emergency
- ∼10–15% of the patients will have associated choledocholithiasis.
- After cholecystectomy, stones may recur in the bile duct.
- Acute cholecystitis (90–95% secondary to gallstones)
- Gallstone pancreatitis
- Common bile duct stones with obstructive jaundice and acute cholangitis
- Biliary-enteric fistula and gallstone ileus; Bouveret syndrome is a variant of gallstone ileus where the gallstone lodges in the duodenum or pylorus causing a gastric outlet obstruction.
- Gallbladder cancer
- Mirizzi syndrome (bile duct obstruction caused by gallstones lodged in gallbladder or cystic duct)
- Bogue CO, Murphy AJ, Gerstle JT, et al. Risk factors, complications, and outcomes of gallstones in children: A single-center review. J Pediatr Gastroenterol Nutr. 2010;50:303–308. [PMID:20118803]
- Brown LM, Rogers SJ, Cello JP, et al. Cost-effective treatments of patients with symptomatic cholelithiasis and possible common bile duct stones. J Am Coll Surg. 2011;212(6):1049–1060. [PMID:21444220]
- Gurusamy KS, Samraj K. Cholecystectomy versus no cholecystectomy in patients with silent gallstones. Cochrane Database Syst Rev. 2007;CD006230. [PMID:17253585]
- Zehetner J, Pelipad D, Darehzereshki A, et al. Single-access laparoscopic cholecystectomy versus classic laparoscopic cholecystectomy: A systematic review and meta-analysis of randomized controlled trials. Surg Laparosc Endosc Percutan Tech. 2013;23(3):235–243. [PMID:23751985]
- Warschkow R, Tarantino I, Ukegjini K, et al. Concomitant cholecystectomy during laparoscopic Roux-en-Y gastric bypass in obese patients is not justified: A meta-analysis. Obes Surg. 2013;23(3):397–407. [PMID:23315094]
- 574.0 Calculus of gallbladder with acute cholecystitis
- 574.00 Calculus of gallbladder with acute cholecystitis, without mention of obstruction
- 574.01 Calculus of gallbladder with acute cholecystitis, with obstruction
- 574.1 Calculus of gallbladder with other cholecystitis
- 574.10 Calculus of gallbladder with other cholecystitis, without mention of obstruction
- 574.11 Calculus of gallbladder with other cholecystitis, with obstruction
- 574.2 Calculus of gallbladder without mention of cholecystitis
- 574.20 Calculus of gallbladder without mention of cholecystitis, without mention of obstruction
- 574.21 Calculus of gallbladder without mention of cholecystitis, with obstruction
- K80.0 Calculus of gallbladder with acute cholecystitis
- K80.00 Calculus of gallbladder w acute cholecyst w/o obstruction
- K80.01 Calculus of gallbladder w acute cholecystitis w obstruction
- K80.18 Calculus of gallbladder w oth cholecystitis w/o obstruction
- K80.19 Calculus of gallbladder w oth cholecystitis with obstruction
- K80.2 Calculus of gallbladder without cholecystitis
- K80.20 Calculus of gallbladder w/o cholecystitis w/o obstruction
- K80.21 Calculus of gallbladder w/o cholecystitis with obstruction
- 266474003 calculus in biliary tract (disorder)
- 29484002 Cholelithiasis AND cholecystitis without obstruction
- 312110005 gallbladder and bile duct calculi (disorder)
- 50450007 Cholelithiasis AND cholecystitis with obstruction
- Laparoscopic cholecystectomy has become the most frequently used procedure; lithotripsy and oral dissolution therapy may be considered in rare circumstances.
- Acute acalculous cholecystitis is associated with bile stasis and gallbladder ischemia.
- Prophylactic cholecystectomy is not indicated in patients with diabetes and asymptomatic gallstones. No evidence suggests that asymptomatic diabetics are at increased risk of developing complications of gallstone disease.
- The best imaging modality for the diagnosis of gallstones is transabdominal US (sensitivity, 97%; specificity, 95%); not sensitive for occult gallstones or microlithiasis (stones <5 mm).
- Think of gallstones in patients complaining of “gas pains” after bariatric surgery as they adjust to their new diet.
Hongyi Cui, MD, PhD, FACS, FICS
- Uy MC, Talingdan-Te MC, Espinosa WZ, et al. Ursodeoxycholic acid in the prevention of gallstone formation after bariatric surgery: A meta-analysis. Obes Surg. 2008;18(12):1532–1538. Epub 2008 Jun 24. [PMID:18574646]
- Sakcak I, Avsar FM, Cosgun E, et al. Management of concurrent cholelithiasis in gastric banding for morbid obesity. Eur J Gastroenterol Hepatol. 2011;23(9):766–769. [PMID:21712718]
- Colli A, Conte D, Valle SD, et al. Meta-analysis: Nonsteroidal anti-inflammatory drugs in biliary colic. Aliment Pharmacol Ther. 2012;35(12):1370–1378. Epub 2012 Apr 29. [PMID:22540869]
- Zhou H, Zhang J, Wang Q, et al. Meta-analysis: Antibiotic prophylaxis in elective laparoscopic cholecystectomy. Aliment Pharmacol Ther. 2009;29:1086–1095. [PMID:19236313]
- Society for Surgery of the Alimentary Tract. SSAT patient care guidelines. Treatment of gallstone and gallbladder disease. J Gastrointest Surg. 2007;11(9):1222–1224. [PMID:18062077]
- Keus F, Gooszen HG, van Laarhoven CJ, et al. Open, small-incision, or laparoscopic cholecystectomy for patients with symptomatic cholecystolithiasis. An overview of Cochrane Hepato-Biliary Group reviews. Cochrane Database Syst Rev. 2010;CD008318. [PMID:20091665]
- Connor S, Garden OJ. Bile duct injury in the era of laparoscopic cholecystectomy. Br J Surg. 2006;93:158–168. [PMID:16432812]
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