Cholelithiasis

Also see Gallstones.

Clinical Features and Natural HistoryTop

Cholelithiasis: Figure 1 in Gallstones.

1. Symptoms of cholelithiasis, when present, include paroxysmal acute abdominal pain—so-called biliary colic—which is the key manifestation of cholelithiasis. It often appears after ingestion of a fatty meal and is caused by elevated pressure in the gallbladder following occlusion of the cystic duct by a gallstone. The pain is located in the right upper abdominal quadrant or in the central epigastrium and can be referred to the right subscapular region. It usually lasts >30 minutes but <5 hours, resolves gradually, and may be accompanied by nausea and vomiting. Other atypical symptoms include heartburn, epigastric discomfort after ingestion of fatty meals, and bloating. Pain persisting >5 hours or fever with rigors may indicate acute cholecystitis, cholangitis, or acute biliary pancreatitis.

2. Signs present during biliary colic include right upper quadrant tenderness and pain on palpation in the right upper abdominal quadrant upon deep inspiration.

3. Natural history: Cholelithiasis is asymptomatic in approximately two-thirds of patients. A third of patients have biliary colic, which recurs every few days, weeks, or months.

DiagnosisTop

Diagnostic Tests

1. Imaging studies: Ultrasonography has a diagnostic reliability of >95%. It is used to visualize gallstones ≥3 mm in diameter, evaluate gallbladder enlargement, measure the diameter of intrahepatic and extrahepatic bile ducts, and assess the adjacent organs.Evidence 1Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to methodologic limitations. Birtwhistle RV, Sauerbrei EE. Ultrasonography in the diagnosis of gallbladder disease. Can Fam Physician. 1983 Sep;29:1621-5. PMID: 21283395; PMCID: PMC2153898. Duncan CB, Riall TS. Evidence-based current surgical practice: calculous gallbladder disease. J Gastrointest Surg. 2012 Nov;16(11):2011-25. doi: 10.1007/s11605-012-2024-1. Epub 2012 Sep 18. Review. PMID: 22986769; PMCID: PMC3496004. Bortoff GA, Chen MY, Ott DJ, Wolfman NT, Routh WD. Gallbladder stones: imaging and intervention. Radiographics. 2000 May-Jun;20(3):751-66. Review. PMID: 10835126. Gallstones may be difficult to differentiate from polyps (these are immobile and cause no acoustic echo) and biliary sludge (this contains cholesterol crystals, causes no acoustic echo, and is mobile when the patient’s position changes). Endoscopic ultrasonography (EUS) and/or magnetic resonance imaging (MRI) can be performed in patients with typical symptoms in whom ultrasonography has not detected gallstones. Plain abdominal radiography may reveal calcified gallstones (present in <20% of patients with stones) and a porcelain (calcified) gallbladder.

2. Laboratory tests: Results are normal in patients with uncomplicated gallstone disease.

Diagnostic Criteria

Typical gallstones are visualized on ultrasonography.

In patients with symptomatic cholelithiasis who are at low risk for choledocholithiasis, no further imaging studies of the biliary tract are indicated.

In patients with a history of acute pancreatitis, those aged >55 years, and those with elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels, EUS or magnetic resonance cholangiopancreatography (MRCP) is indicated before planned surgery; an alternative is intraoperative cholangiography.

Differential Diagnosis

Other causes of acute epigastric pain: peptic ulcer disease, perforated gastric or duodenal ulcer, acute and chronic pancreatitis, pleurisy, pericarditis, acute appendicitis, acute myocardial infarction, dissecting aortic aneurysm.

Features seen on ultrasonography require differentiation from gallbladder polyps and biliary sludge (see Diagnostic Tests, above).

TreatmentTop

Treatment of Biliary Colic

1. Analgesics: Acetaminophen (INN paracetamol) and nonsteroidal anti-inflammatory drugs (NSAIDs) at typical doses. In patients with severe pain, use opioids: IM or subcutaneous meperidine (INN pethidine) 50 to 100 mg or IM pentazocine 30 to 60 mg.

2. Spasmolytic agents (hyoscine-N-butylbromide).Evidence 2Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to imprecision. Kumar A, Deed JS, Bhasin B, Kumar A, Thomas S. Comparison of the effect of diclofenac with hyoscine-N-butylbromide in the symptomatic treatment of acute biliary colic. ANZ J Surg. 2004 Jul;74(7):573-6. PMID: 15230794.

Surgical Treatment

Surgical treatment is indicated in patients with symptomatic cholelithiasis and its complications.

1. Laparoscopic rather than open cholecystectomy is the preferred technique.Evidence 3Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). High Quality of Evidence (high confidence that we know true effects of the intervention). Keus F, de Jong JA, Gooszen HG, van Laarhoven CJ. Laparoscopic versus open cholecystectomy for patients with symptomatic cholecystolithiasis. Cochrane Database Syst Rev. 2006 Oct 18;(4):CD006231. Review. PMID: 17054285. The procedure is contraindicated in patients with multiple prior surgical procedures or with diffuse peritonitis. Approximately ~5% of patients undergoing laparoscopic cholecystectomy require conversion to open surgery. In patients with concomitant cholelithiasis and choledocholithiasis, endoscopic retrograde cholangiopancreatography (ERCP) should be performed with endoscopic sphincterotomy and evacuation of gallstones from the bile ducts before the planned laparoscopic cholecystectomy.Evidence 4Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to imprecision and inclusion of some observational data. Sahoo MR, Kumar AT, Patnaik A. Randomised study on single stage laparo-endoscopic rendezvous (intra-operative ERCP) procedure versus two stage approach (Pre-operative ERCP followed by laparoscopic cholecystectomy) for the management of cholelithiasis with choledocholithiasis. J Minim Access Surg. 2014 Jul;10(3):139-43. doi: 10.4103/0972-9941.134877. PMID: 25013330; PMCID: PMC4083546. Saccomani G, Durante V, Magnolia MR, et al. Combined endoscopic treatment for cholelithiasis associated with choledocholithiasis. Surg Endosc. 2005 Jul;19(7):910-4. Epub 2005 May 3. PMID: 15868278.

2. Open cholecystectomy is indicated in patients with contraindications to laparoscopy.

3. Prophylactic cholecystectomy in asymptomatic cholelithiasis is controversial. Suggested indications include sickle cell anemia, immunosuppression, body mass index ≥40 kg/m2 (cholecystectomy during bariatric surgery), and porcelain gallbladder (because of a 25% increase in the risk of cancer).Evidence 5Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to methodologic limitations. McCarty TR, Farrelly J, Njei B, Jamidar P, Muniraj T. Role of Prophylactic Cholecystectomy After Endoscopic Sphincterotomy for Biliary Stone Disease: A Systematic Review and Meta-analysis. Ann Surg. 2021 Apr 1;273(4):667-675. doi: 10.1097/SLA.0000000000003977. PMID: 32590541. Muroni M, Loi V, Lionnet F, Girot R, Houry S. Prophylactic laparoscopic cholecystectomy in adult sickle cell disease patients with cholelithiasis: A prospective cohort study. Int J Surg. 2015 Oct;22:62-6. doi: 10.1016/j.ijsu.2015.07.708. Epub 2015 Aug 14. PMID: 26278661. Graham SM, Flowers JL, Schweitzer E, Bartlett ST, Imbembo AL. The utility of prophylactic laparoscopic cholecystectomy in transplant candidates. Am J Surg. 1995 Jan;169(1):44-8; discussion 48-9. PMID: 7817997. Amstutz S, Michel JM, Kopp S, Egger B. Potential Benefits of Prophylactic Cholecystectomy in Patients Undergoing Bariatric Bypass Surgery. Obes Surg. 2015 Nov;25(11):2054-60. doi: 10.1007/s11695-015-1650-6. PMID: 25804356. Chen GL, Akmal Y, DiFronzo AL, Vuong B, O'Connor V. Porcelain Gallbladder: No Longer an Indication for Prophylactic Cholecystectomy. Am Surg. 2015 Oct;81(10):936-40. PMID: 26463284.

Pharmacotherapy

In patients with contraindications to surgery, use oral ursodiol (INN ursodeoxycholic acid) 8 to 12 mg/kg/d in 2 to 3 divided doses taken with meals.Evidence 6Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to methodologic limitations. Uy MC, Talingdan-Te MC, Espinosa WZ, Daez ML, Ong JP. Ursodeoxycholic acid in the prevention of gallstone formation after bariatric surgery: a meta-analysis. Obes Surg. 2008 Dec;18(12):1532-8. doi: 10.1007/s11695-008-9587-7. Epub 2008 Jun 24. PMID: 18574646. Salen G. Gallstone dissolution therapy with ursodiol. Efficacy and safety. Dig Dis Sci. 1989 Dec;34(12 Suppl):39S-43S. PMID: 2689115. Bellows CF, Berger DH, Crass RA. Management of gallstones. Am Fam Physician. 2005 Aug 15;72(4):637-42. Review. PMID: 16127953. Treatment lasts 6 to 24 months, with the first evaluation of efficacy at 6 months. Continue treatment for 3 months after confirming dissolution of gallstones; discontinue treatment if there is no improvement at 9 months. In ~50% of patients cholelithiasis recurs.

Do not use ursodiol in patients with pigment or calcified gallstones >15 mm in diameter, pregnant women, patients with concomitant liver disease, or patients with severe clinical manifestations of cholelithiasis.

Ursodiol can also be used for prevention of gallstone formation (eg, during the rapid weight loss period following bariatric surgery until the weight stabilizes).

ComplicationsTop

1. Acute cholecystitis (see Acute Cholecystitis).

2. Chronic cholecystitis is a morphologic diagnosis based on finding a thick-walled, fibrotic, deformed gallbladder, which is a result of mechanical irritation of the gallbladder by gallstones or recurrent attacks of biliary colic.

Signs and symptoms include pain of varying severity that is located in the right upper abdominal quadrant and central epigastrium and referred to the back and right scapula. Concomitant cholelithiasis may be associated with recurrent biliary colic, episodes of recurrent acute pancreatitis, choledocholithiasis, and cholecystitis.

Diagnosis is based on ultrasonographic findings, which reveal gallstones in the gallbladder and thickened gallbladder walls.

Treatment: In symptomatic patients perform laparoscopic or open cholecystectomy.