Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Uncomplicated gallstone disease in adults

Salam F Zakko, MD, FACP
Section Editor
Sanjiv Chopra, MD, MACP
Deputy Editor
Anne C Travis, MD, MSc, FACG, AGAF


Gallstones are common, particularly in Western populations (table 1). In the United States, gallstones are seen in approximately 6 percent of men and 9 percent of women. Most individuals with gallstones are asymptomatic throughout their lives. When the stones start causing symptoms, the condition is referred to as gallstone disease. Uncomplicated gallstone disease refers to stones in the gallbladder that are associated with biliary colic in the absence of complications such as acute cholecystitis, cholangitis, or gallstone pancreatitis.

Determining whether a patient's upper digestive symptoms are the result of gallstones detected on imaging can be challenging. While both gallstones and upper digestive symptoms are common in the general population, they are not always related. Differentiating patients with uncomplicated gallstone disease from those with other disorders and an incidental finding of gallstones is important since cholecystectomy is often curative in those with symptomatic gallstones, but it exposes those with incidental gallstones to unnecessary risk, delays appropriate treatment for the actual cause of symptoms, and incurs unnecessary expense.

This topic will review uncomplicated gallstone disease. The epidemiology of and risk factors for gallstones, the approach to patients with an incidental finding of gallstones, gallstone disease in pregnant women, and the complications of gallstone disease are discussed separately. (See "Epidemiology of and risk factors for gallstones" and "Approach to the patient with incidental gallstones" and "Gallstones in pregnancy" and "Acute cholecystitis: Pathogenesis, clinical features, and diagnosis" and "Etiology of acute pancreatitis", section on 'Gallstones' and "Acute cholangitis" and "Choledocholithiasis: Clinical manifestations, diagnosis, and management".)

The discussion that follows is generally consistent with guidelines from the National Institute for Health and Care Excellence [1].


When considering gallstone disease, we have found it helpful to categorize patients into the following clinical groups:


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2016. | This topic last updated: Apr 21, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. Warttig S, Ward S, Rogers G, Guideline Development Group. Diagnosis and management of gallstone disease: summary of NICE guidance. BMJ 2014; 349:g6241.
  2. Gracie WA, Ransohoff DF. The natural history of silent gallstones: the innocent gallstone is not a myth. N Engl J Med 1982; 307:798.
  3. Festi D, Reggiani ML, Attili AF, et al. Natural history of gallstone disease: Expectant management or active treatment? Results from a population-based cohort study. J Gastroenterol Hepatol 2010; 25:719.
  4. Ransohoff DF, Gracie WA. Treatment of gallstones. Ann Intern Med 1993; 119:606.
  5. Thistle JL, Cleary PA, Lachin JM, et al. The natural history of cholelithiasis: the National Cooperative Gallstone Study. Ann Intern Med 1984; 101:171.
  6. Attili AF, De Santis A, Capri R, et al. The natural history of gallstones: the GREPCO experience. The GREPCO Group. Hepatology 1995; 21:655.
  7. Barbara L, Sama C, Morselli Labate AM, et al. A population study on the prevalence of gallstone disease: the Sirmione Study. Hepatology 1987; 7:913.
  8. Friedman GD. Natural history of asymptomatic and symptomatic gallstones. Am J Surg 1993; 165:399.
  9. Friedman GD, Raviola CA, Fireman B. Prognosis of gallstones with mild or no symptoms: 25 years of follow-up in a health maintenance organization. J Clin Epidemiol 1989; 42:127.
  10. Diehl AK, Sugarek NJ, Todd KH. Clinical evaluation for gallstone disease: usefulness of symptoms and signs in diagnosis. Am J Med 1990; 89:29.
  11. LUND J. Surgical indications in cholelithiasis: prophylactic choleithiasis: prophylactic cholecystectomy elucidated on the basis of long-term follow up on 526 nonoperated cases. Ann Surg 1960; 151:153.
  12. Festi D, Sottili S, Colecchia A, et al. Clinical manifestations of gallstone disease: evidence from the multicenter Italian study on cholelithiasis (MICOL). Hepatology 1999; 30:839.
  13. Rigas B, Torosis J, McDougall CJ, et al. The circadian rhythm of biliary colic. J Clin Gastroenterol 1990; 12:409.
  14. Minoli G, Imperiale G, Spinzi GC, et al. Circadian periodicity and other clinical features of biliary pain. J Clin Gastroenterol 1991; 13:546.
  15. Zakko SF, Guttermuth MC, Jamali SH, et al. A population study of gallstone composition, symptoms, and outcomes after cholecystectomy (abstract). Gastroenterology 1999; 116:A43.
  16. Berger MY, Olde Hartman TC, Bohnen AM. Abdominal symptoms: do they disappear after cholecystectomy? Surg Endosc 2003; 17:1723.
  17. Johnson CD. ABC of the upper gastrointestinal tract. Upper abdominal pain: Gall bladder. BMJ 2001; 323:1170.
  18. Barakos JA, Ralls PW, Lapin SA, et al. Cholelithiasis: evaluation with CT. Radiology 1987; 162:415.
  19. Benarroch-Gampel J, Boyd CA, Sheffield KM, et al. Overuse of CT in patients with complicated gallstone disease. J Am Coll Surg 2011; 213:524.
  20. Leopold GR, Amberg J, Gosink BB, Mittelstaedt C. Gray scale ultrasonic cholecystography: a comparison with conventional radiographic techniques. Radiology 1976; 121:445.
  21. Conrad MR, Janes JO, Dietchy J. Significance of low level echoes within the gallbladder. AJR Am J Roentgenol 1979; 132:967.
  22. Brink JA, Simeone JF, Mueller PR, et al. Physical characteristics of gallstones removed at cholecystectomy: implications for extracorporeal shock-wave lithotripsy. AJR Am J Roentgenol 1988; 151:927.
  23. Filly RA, Allen B, Minton MJ, et al. In vitro investigation of the origin of echoes with biliary sludge. J Clin Ultrasound 1980; 8:193.
  24. Ko CW, Sekijima JH, Lee SP. Biliary sludge. Ann Intern Med 1999; 130:301.
  25. Lee SP, Nicholls JF. Nature and composition of biliary sludge. Gastroenterology 1986; 90:677.
  26. Venu RP, Geenen JE, Hogan W, et al. Idiopathic recurrent pancreatitis. An approach to diagnosis and treatment. Dig Dis Sci 1989; 34:56.
  27. Lee SP, Maher K, Nicholls JF. Origin and fate of biliary sludge. Gastroenterology 1988; 94:170.
  28. Lee SP, Nicholls JF, Park HZ. Biliary sludge as a cause of acute pancreatitis. N Engl J Med 1992; 326:589.
  29. Neoptolemos JP, Davidson BR, Winder AF, Vallance D. Role of duodenal bile crystal analysis in the investigation of 'idiopathic' pancreatitis. Br J Surg 1988; 75:450.
  30. Geenen JE, Nash JA. The role of sphincter of Oddi manometry and biliary microscopy in evaluating idiopathic recurrent pancreatitis. Endoscopy 1998; 30:A237.
  31. Britten JS, Golding RH, Cooperberg PL. Sludge balls to gallstones. J Ultrasound Med 1984; 3:81.
  32. Feuerstein IM, Shawker TH, Savarese DM. CT demonstration of calcifying sludge balls. J Comput Assist Tomogr 1990; 14:325.
  33. Shea JA, Berlin JA, Escarce JJ, et al. Revised estimates of diagnostic test sensitivity and specificity in suspected biliary tract disease. Arch Intern Med 1994; 154:2573.
  34. Garra BS, Davros WJ, Lack EE, et al. Visibility of gallstone fragments at US and fluoroscopy: implications for monitoring gallstone lithotripsy. Radiology 1990; 174:343.
  35. Wermke W. [Ultrasonic diagnosis of gallstone diseases]. Z Gesamte Inn Med 1989; 44:377.
  36. Kurol M, Forsberg L. Ultrasonography in the diagnosis of acute cholecystitis. Acta Radiol Diagn (Stockh) 1984; 25:379.
  37. Venu RP, Geenen JE, Toouli J, et al. Endoscopic retrograde cholangiopancreatography. Diagnosis of cholelithiasis in patients with normal gallbladder x-ray and ultrasound studies. JAMA 1983; 249:758.
  38. Zakko SF, Srb S, Ramsby GR. Sensitivity of percutaneous endoscopy compared with ultrasonography in the detection of residue or mucosal lesions after topical gallbladder stone dissolution. Gastrointest Endosc 1995; 42:434.
  39. Neoptolemos JP, Hall AW, Finlay DF, et al. The urgent diagnosis of gallstones in acute pancreatitis: a prospective study of three methods. Br J Surg 1984; 71:230.
  40. Dahan P, Andant C, Lévy P, et al. Prospective evaluation of endoscopic ultrasonography and microscopic examination of duodenal bile in the diagnosis of cholecystolithiasis in 45 patients with normal conventional ultrasonography. Gut 1996; 38:277.
  41. Liu CL, Lo CM, Chan JK, et al. EUS for detection of occult cholelithiasis in patients with idiopathic pancreatitis. Gastrointest Endosc 2000; 51:28.
  42. Dill JE, Hill S, Callis J, et al. Combined endoscopic ultrasound and stimulated biliary drainage in cholecystitis and microlithiasis--diagnoses and outcomes. Endoscopy 1995; 27:424.
  43. Norton SA, Alderson D. The value of endoscopic ultrasonography (EUS) in the assessment of idiopathic pancreatitis. In: Program and Abstracts, 11th International Symposium on Endoscopic Ultrasonography, Kyoto, Japan 1998. p.39.
  44. Delchier JC, Benfredj P, Preaux AM, et al. The usefulness of microscopic bile examination in patients with suspected microlithiasis: a prospective evaluation. Hepatology 1986; 6:118.
  45. Moskovitz M, Min TC, Gavaler JS. The microscopic examination of bile in patients with biliary pain and negative imaging tests. Am J Gastroenterol 1986; 81:329.
  46. Burnstein MJ, Vassal KP, Strasberg SM. Results of combined biliary drainage and cholecystokinin cholecystography in 81 patients with normal oral cholecystograms. Ann Surg 1982; 196:627.
  47. Ramond MJ, Dumont M, Belghiti J, Erlinger S. Sensitivity and specificity of microscopic examination of gallbladder bile for gallstone recognition and identification. Gastroenterology 1988; 95:1339.
  48. Sedaghat A, Grundy SM. Cholesterol crystals and the formation of cholesterol gallstones. N Engl J Med 1980; 302:1274.
  49. Gollish SH, Burnstein MJ, Ilson RG, et al. Nucleation of cholesterol monohydrate crystals from hepatic and gall-bladder bile of patients with cholesterol gall stones. Gut 1983; 24:836.
  50. Abeysuriya V, Deen KI, Navarathne NM. Biliary microlithiasis, sludge, crystals, microcrystallization, and usefulness of assessment of nucleation time. Hepatobiliary Pancreat Dis Int 2010; 9:248.
  51. Rashdan A, Fogel E, McHenry L Jr, et al. Frequency of biliary crystals in patients with suspected sphincter of Oddi dysfunction. Gastrointest Endosc 2003; 58:875.
  52. Corazziari E, Shaffer EA, Hogan WJ, et al. Functional disorders of the biliary tract and Pancreas. Gut 1999; 45 Suppl 2:1148.
  53. Ziessman HA, Fahey FH, Hixson DJ. Calculation of a gallbladder ejection fraction: advantage of continuous sincalide infusion over the three-minute infusion method. J Nucl Med 1992; 33:537.
  54. Marks JW, Bonorris G. Intermittency of cholesterol crystals in duodenal bile from gallstone patients. Gastroenterology 1984; 87:622.
  55. Graham EA, Cole WH, Copher GH. Visualization of the gallbladder by the sodium salt of tetrabromophthalein. JAMA 1924; 82:1777.
  56. Kraag N, Thijs C, Knipschild P. Dyspepsia--how noisy are gallstones? A meta-analysis of epidemiologic studies of biliary pain, dyspeptic symptoms, and food intolerance. Scand J Gastroenterol 1995; 30:411.
  57. Berger MY, van der Velden JJ, Lijmer JG, et al. Abdominal symptoms: do they predict gallstones? A systematic review. Scand J Gastroenterol 2000; 35:70.
  58. Leitzmann MF, Rimm EB, Willett WC, et al. Recreational physical activity and the risk of cholecystectomy in women. N Engl J Med 1999; 341:777.
  59. Leitzmann MF, Giovannucci EL, Rimm EB, et al. The relation of physical activity to risk for symptomatic gallstone disease in men. Ann Intern Med 1998; 128:417.
  60. Colli A, Conte D, Valle SD, et al. Meta-analysis: nonsteroidal anti-inflammatory drugs in biliary colic. Aliment Pharmacol Ther 2012; 35:1370.
  61. Henderson SO, Swadron S, Newton E. Comparison of intravenous ketorolac and meperidine in the treatment of biliary colic. J Emerg Med 2002; 23:237.
  62. Akriviadis EA, Hatzigavriel M, Kapnias D, et al. Treatment of biliary colic with diclofenac: a randomized, double-blind, placebo-controlled study. Gastroenterology 1997; 113:225.
  63. Elta GH, Barnett JL. Meperidine need not be proscribed during sphincter of Oddi manometry. Gastrointest Endosc 1994; 40:7.
  64. Thompson DR. Narcotic analgesic effects on the sphincter of Oddi: a review of the data and therapeutic implications in treating pancreatitis. Am J Gastroenterol 2001; 96:1266.
  65. Thune A, Baker RA, Saccone GT, et al. Differing effects of pethidine and morphine on human sphincter of Oddi motility. Br J Surg 1990; 77:992.
  66. Tytgat GN. Hyoscine butylbromide - a review on its parenteral use in acute abdominal spasm and as an aid in abdominal diagnostic and therapeutic procedures. Curr Med Res Opin 2008; 24:3159.
  67. Tomida S, Abei M, Yamaguchi T, et al. Long-term ursodeoxycholic acid therapy is associated with reduced risk of biliary pain and acute cholecystitis in patients with gallbladder stones: a cohort analysis. Hepatology 1999; 30:6.
  68. Dimou FM, Adhikari D, Mehta HB, Riall TS. Trends in Follow-Up of Patients Presenting to the Emergency Department with Symptomatic Cholelithiasis. J Am Coll Surg 2016; 222:377.
  69. Soper NJ, Stockmann PT, Dunnegan DL, Ashley SW. Laparoscopic cholecystectomy. The new 'gold standard'? Arch Surg 1992; 127:917.
  70. Schirmer BD, Edge SB, Dix J, et al. Laparoscopic cholecystectomy. Treatment of choice for symptomatic cholelithiasis. Ann Surg 1991; 213:665.
  71. Wiesen SM, Unger SW, Barkin JS, et al. Laparoscopic cholecystectomy: the procedure of choice for acute cholecystitis. Am J Gastroenterol 1993; 88:334.
  72. Wilson RG, Macintyre IM, Nixon SJ, et al. Laparoscopic cholecystectomy as a safe and effective treatment for severe acute cholecystitis. BMJ 1992; 305:394.
  73. Yamashita Y, Takada T, Kawarada Y, et al. Surgical treatment of patients with acute cholecystitis: Tokyo Guidelines. J Hepatobiliary Pancreat Surg 2007; 14:91.
  74. Bernard HR, Hartman TW. Complications after laparoscopic cholecystectomy. Am J Surg 1993; 165:533.
  75. National Institutes of Health Consensus Development Conference Statement on Gallstones and Laparoscopic Cholecystectomy. Am J Surg 1993; 165:390.
  76. Thistle JL, Longstreth GF, Romero Y, et al. Factors that predict relief from upper abdominal pain after cholecystectomy. Clin Gastroenterol Hepatol 2011; 9:891.
  77. Giovannucci E, Colditz GA, Stampfer MJ. A meta-analysis of cholecystectomy and risk of colorectal cancer. Gastroenterology 1993; 105:130.
  78. Shao T, Yang YX. Cholecystectomy and the risk of colorectal cancer. Am J Gastroenterol 2005; 100:1813.
  79. Lagergren J, Ye W, Ekbom A. Intestinal cancer after cholecystectomy: is bile involved in carcinogenesis? Gastroenterology 2001; 121:542.
  80. Tint GS, Salen G, Colalillo A, et al. Ursodeoxycholic acid: a safe and effective agent for dissolving cholesterol gallstones. Ann Intern Med 1982; 97:351.
  81. Rubin RA, Kowalski TE, Khandelwal M, Malet PF. Ursodiol for hepatobiliary disorders. Ann Intern Med 1994; 121:207.