Cholelithiasis

Author: Douglas M Heuman, MD, FACP, FACG, AGAF, Chief of Hepatology, Hunter Holmes McGuire Department of Veterans Affairs Medical Center; Professor, Department of Internal Medicine, Division of Gastroenterology, Virginia Commonwealth University School of Medicine Coauthor(s): Anastasios A Mihas, MD, DMSc, FACP, FACG, Professor, Department of Medicine, Division of Gastroenterology, Virginia Commonwealth University School of Medicine; Consulting Staff, Virginia Commonwealth University Hospitals and Clinics; Chief of GI Clinical Research, Director of GI Outpatient Service, Associate Director of Hepatology, Hunter Holmes McGuire Veterans Affairs Medical Center; Jeff Allen, MD, Assistant Professor, Department of Surgery, University of Louisville Contributor Information and Disclosures
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Updated: Mar 17, 2010

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Introduction
Background
Gallstones are concretions that form in the biliary tract, usually in the gallbladder (see image below).

Cholelithiasis. A gallbladder filled with gallstones (examined extracorporally after laparoscopic cholecystectomy [LC]). [ CLOSE WINDOW ]

Cholelithiasis. A gallbladder filled with gallstones (examined extracorporally after laparoscopic cholecystectomy [LC]). Their development is insidious, and they may remain asymptomatic for decades. Migration of gallstones may lead to occlusion of the biliary and pancreatic ducts, causing pain (biliary colic) and producing acute complications, such as acute cholecystitis, ascending cholangitis, or acute pancreatitis.1,2 Chronic gallstone disease may lead to fibrosis and loss of function of the gallbladder and predisposes to gallbladder cancer. Excision of the gallbladder (cholecystectomy) to cure gallstone disease is among the most frequently performed abdominal surgical procedures.

Pathophysiology

Gallstone formation occurs because certain substances in bile are present in concentrations that approach the limits of their solubility. When bile is concentrated in the gallbladder, it can become supersaturated with these substances, which then precipitate from solution as microscopic crystals. The crystals are trapped in gallbladder mucus, producing gallbladder sludge. Over time, the crystals grow, aggregate, and fuse to form macroscopic stones. Occlusion of the ducts by sludge and stones produces the complications of gallstone disease. The 2 main substances involved in gallstone formation are cholesterol and calcium bilirubinate. Cholesterol gallstones More than 80% of gallstones in the United States contain cholesterol as their major component. Liver cells secrete cholesterol into bile along with phospholipid (lecithin) in the form of small spherical membranous bubbles, termed unilamellar vesicles. Liver cells also secrete bile salts, which are powerful detergents required for digestion and absorption of dietary fats. Bile salts in bile dissolve the unilamellar vesicles to form soluble aggregates called mixed micelles. This happens mainly in the gallbladder, where bile is concentrated by reabsorption of electrolytes and water. Compared with vesicles (which can hold up to 1 molecule of cholesterol for every molecule of lecithin), mixed micelles have a lower carrying capacity for cholesterol (about 1 molecule of cholesterol for every 3 molecules of lecithin). If bile contains a relatively high proportion of cholesterol to begin with, then as bile is concentrated, progressive dissolution of vesicles may lead to a state in which the cholesterol carrying capacity of the micelles and residual vesicles is exceeded. At this point, bile is supersaturated with cholesterol, and cholesterol monohydrate crystals may form. Thus, the main factors that determine whether cholesterol gallstones will form are: (1) the amount of cholesterol secreted by liver cells, relative to lecithin and bile salts, and (2) the degree of concentration and extent of stasis of bile in the gallbladder. Calcium, bilirubin, and pigment gallstones Bilirubin, a yellow pigment derived from the breakdown of heme, is actively secreted into bile by liver cells. Most of the bilirubin in bile is in the form of glucuronide conjugates, which are quite water soluble and stable, but a small proportion consists of unconjugated bilirubin. Unconjugated bilirubin, like fatty acids, phosphate, carbonate, and other anions, tends to form insoluble precipitates with calcium. Calcium enters bile passively along with other electrolytes. In situations of high heme turnover, such as chronic hemolysis or cirrhosis, unconjugated bilirubin may be present in bile at higher than normal concentrations. Calcium bilirubinate may then crystallize from solution and eventually form stones. Over time, various oxidations cause the bilirubin precipitates to take on a jet black color, and stones

formed in this manner are termed black pigment stones. Black pigment stones represent 10-20% of gallstones in the United States. Bile is normally sterile, but, in some unusual circumstances (eg, above a biliary stricture), it may become colonized with bacteria. The bacteria hydrolyze conjugated bilirubin, and the resulting increase in unconjugated bilirubin may lead to precipitation of calcium bilirubinate crystals. Bacterial hydrolysis of lecithin leads to the release of fatty acids, which complex with calcium and precipitate from solution. The resulting concretions have a claylike consistency and are termed brown pigment stones. Unlike cholesterol or black pigment stones, which form almost exclusively in the gallbladder, brown pigment stones often form de novo in the bile ducts. Brown pigment stones are unusual in the United States but are fairly common in some parts of Southeast Asia, possibly related to liver flukes. Mixed gallstones Cholesterol gallstones may become colonized with bacteria and can elicit gallbladder mucosal inflammation. Lytic enzymes from bacteria and leukocytes hydrolyze bilirubin conjugates and fatty acids. As a result, over time, cholesterol stones may accumulate a substantial proportion of calcium bilirubinate and other calcium salts, producing mixed gallstones. Large stones may develop a surface rim of calcium resembling an eggshell that may be visible on plain x-ray films.

Frequency
United States Gallstones are uncommon in children. Beginning at puberty, the concentration of cholesterol in bile increases. After age 15 years, the prevalence of gallstones in US women increases by about 1% per year; in men, the rate is less, about 0.5% per year. The incidence in women falls with menopause, but new stone formation in men and women continues at a rate of about 0.4% per year until late in life. The lifetime risk of developing gallstones in white individuals is 50% for women and 30% for men. Prevalence in Mexican Americans and Native Americans is similar, whereas black individuals have a somewhat lower risk. International The prevalence of cholesterol cholelithiasis in other Western cultures is similar to that in the United States, but it appears to be somewhat lower in Asia and Africa. A Swedish epidemiologic study found that the incidence of gallstones was 1.39 per 100 person-years.3 In a study of randomly selected individuals aged 35-85 years in a general population who had been screened previously with ultrasonography and found to have no gallbladder stones, Halldestam et al reexamined 503 study subjects after a minimum

interval of 5 years. On reexamination, 8.3% (42/503) had developed gallstones. Gallstone development was related to length of follow-up and low-density lipoprotein (LDL) cholesterol levels, and inversely related to alcohol consumption.3

Mortality/Morbidity
Each year, in the United States, approximately 500,000 people develop symptoms or complications of gallstones requiring cholecystectomy. Gallstone disease is responsible for about 10,000 deaths per year in the United States. About 7000 deaths are attributable to acute gallstone complications, such as acute pancreatitis. About 2000-3000 deaths are caused by gallbladder cancers (80% of which occur in the setting of gallstone disease with chronic cholecystitis). Although gallstone surgery is relatively safe, cholecystectomy is a very common procedure, and its rare complications result in several hundred deaths each year.

Race
White individuals, Mexican Americans, and Native Americans have a relatively high prevalence of gallstones. Gallstone disease is less common in Asians and Africans and their descendants.

Sex
Women are more likely to develop cholesterol gallstones than men, especially during their reproductive years, when the incidence of gallstones in women is 2 to 3 times that in men. The difference appears to be attributable mainly to estrogen, which increases biliary cholesterol secretion.4 Pigment gallstones affect men and women equally.

Age
Gallstones continue to form throughout adult life, and the prevalence is greatest at advanced age.

Clinical
History
Gallstone disease may be thought of as having the following 4 stages: (1) the lithogenic state, in which conditions favor gallstone formation; (2) asymptomatic gallstones; (3) symptomatic gallstones, characterized by episodes of biliary colic; and (4) complicated cholelithiasis. Symptoms and complications of gallstone disease result from effects occurring within the gallbladder or from stones that escape the gallbladder to lodge in the common bile duct.

Asymptomatic gallstones

Gallstones may be present in the gallbladder for decades without causing symptoms or complications. In patients with asymptomatic gallstones discovered incidentally, the likelihood of developing symptoms or complications is 1-2% per year. In most cases, asymptomatic gallstones do not require any treatment. o Because they are common, gallstones often coexist with other gastrointestinal conditions. There is little evidence to support a causal association between gallstones and chronic abdominal pain, heartburn, postprandial distress, bloating, flatulence, constipation, or diarrhea. Dyspepsia that occurs reproducibly following ingestion of fatty foods is often wrongly attributed to gallstones, when irritable bowel syndrome or gastroesophageal reflux is the true culprit. Gallstones discovered during an evaluation for nonspecific symptoms are usually innocent bystanders, and treatment directed at the gallstones is unlikely to relieve these symptoms. Biliary colic o Pain termed biliary colic occurs when gallstones fortuitously impact in the cystic duct during a gallbladder contraction, increasing gallbladder wall tension. In most cases, the pain resolves over 30 to 90 minutes as the gallbladder relaxes and the obstruction is relieved. o Episodes of biliary colic are sporadic and unpredictable. The patient localizes the pain to the epigastrium or right upper quadrant and may describe radiation to the right scapular tip. From onset, the pain increases steadily over about 10 to 20 minutes and then gradually wanes. The pain is constant in nature and is not relieved by emesis, antacids, defecation, or positional changes. It may be accompanied by nausea and vomiting. Complications of gallbladder stones o Acute cholecystitis occurs when persistent stone impaction in the cystic duct causes the gallbladder to become distended and progressively inflamed. Patients experience the pain of biliary colic, but, instead of resolving spontaneously, the pain persists and worsens. Overgrowth of colonizing bacteria in the gallbladder often occurs, and, in severe cases, accumulation of pus in the gallbladder, termed gallbladder empyema, occurs. The gallbladder wall may become necrotic, resulting in perforation and pericholecystic abscess. Acute cholecystitis is considered a surgical emergency, although pain and inflammation may subside with conservative measures, such as hydration and antibiotics. o Chronically, gallstones may cause progressive fibrosis of the gallbladder wall and loss of gallbladder function, termed chronic cholecystitis. The pathogenesis of this complication is not completely understood. Repeated attacks of acute cholecystitis may play a role, as may localized ischemia produced by pressure of stones against the gallbladder wall. The chronically fibrotic gallbladder may become shrunken and adherent to adjacent viscera. o Gallbladder adenocarcinoma is an uncommon cancer that usually develops in the setting of gallstones and chronic cholecystitis. Gallbladder cancers
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commonly invade the adjacent liver and common bile duct, producing jaundice. The prognosis is poor unless the cancer is localized to the gallbladder, in which case cholecystectomy may be curative. o Occasionally, a large stone may erode through the wall of the gallbladder into an adjacent viscus (typically the duodenum), producing a cholecystoenteric fistula. The stone, if sufficiently large, may obstruct the small intestine, usually at the level of the ileum, a phenomenon termed gallstone ileus. Complications of stones in the common bile duct o Gallstones are initially retained in the gallbladder by the spiral valves of the cystic duct. Following episodes of gallstone impaction in the cystic duct, these valves may become obliterated and stones may pass into the common bile duct. Patients who have passed one stone tend to pass more stones over the subsequent months. o Stones in the common bile duct may be asymptomatic, but, more commonly, they impact distally in the ampulla of Vater. This may produce biliary colic indistinguishable from that caused by cystic duct stones. Because impaction of common bile duct stones occludes the flow of bile from the liver to the intestine, pressure rises in the intrahepatic bile ducts, leading to increased liver enzymes and jaundice. o Bacterial overgrowth in stagnant bile above an obstructing common duct stone produces purulent inflammation of the liver and biliary tree, termed ascending cholangitis. Characteristic features include the Charcot triad of fever, jaundice, and right upper quadrant pain. Patients may rapidly develop septic shock unless ductal obstruction is relieved. o A stone impacted in the ampulla of Vater may transiently obstruct the pancreatic duct, leading to in situ activation of pancreatic proteases and triggering an attack of acute pancreatitis. o Stone impaction in the distal common bile duct is often relieved spontaneously within hours to days by passage of the stone into the intestine.

Physical
Patients with the lithogenic state or asymptomatic gallstones have no abnormal findings on physical examination.

During attacks of biliary colic, and especially in acute cholecystitis, patients may experience tenderness to palpation over the gallbladder. This can be elicited by having the patient inhale while the examiner maintains steady pressure below the right costal margin (Murphy sign). Localized rebound tenderness, guarding, or rigidity may occur with pericholecystic inflammation. Patients with acute cholecystitis, ascending cholangitis, or acute pancreatitis, in addition to abdominal pain, may exhibit fever and may be tachycardic and hypotensive. In severe cases, bowel sounds are often absent or hypoactive.

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Choledocholithiasis with obstruction of the common bile duct produces cutaneous and scleral icterus that evolves over hours to days as bilirubin accumulates. The Charcot triad of severe right upper quadrant tenderness with jaundice and fever is characteristic of ascending cholangitis. Acute gallstone pancreatitis is often characterized by epigastric tenderness. In severe cases, retroperitoneal hemorrhage may produce ecchymoses of the flanks and periumbilical ecchymoses (Cullen sign and Grey-Turner sign).

Causes
Cholesterol gallstones, black pigment gallstones, and brown pigment gallstones have different pathogenesis and different risk factors, which will be discussed separately.

Cholesterol gallstones are associated with female gender, European or Native American ancestry, and increasing age, as discussed above. Other risk factors include the following: o Obesity: The metabolic syndrome of truncal obesity, insulin resistance, type II diabetes mellitus, hypertension, and hyperlipidemia is associated with increased hepatic cholesterol secretion and is a major risk factor for the development of cholesterol gallstones. o Pregnancy: Cholesterol gallstones are more common in women who have experienced multiple pregnancies. A major contributing factor is thought to be the high progesterone levels of pregnancy. Progesterone reduces gallbladder contractility, leading to prolonged retention and greater concentration of bile in the gallbladder. o Gallbladder stasis: Other causes of gallbladder stasis associated with increased risk of gallstones include high spinal cord injuries, prolonged fasting with total parenteral nutrition, and rapid weight loss associated with severe caloric and fat restriction (eg, diet, gastric bypass surgery). o Drugs: Estrogens administered for contraception or for treatment of prostate cancer increase the risk of cholesterol gallstones. Clofibrate and other fibrate hypolipidemic drugs increase hepatic elimination of cholesterol via biliary secretion and appear to increase the risk of cholesterol gallstones. Somatostatin analogues appear to predispose to gallstones by decreasing gallbladder emptying. o Heredity: About 25% of the predisposition to cholesterol gallstones appears to be hereditary, as judged from studies of identical and fraternal twins. At least a dozen genes may contribute to the risk. A rare syndrome of low phospholipid-associated cholelithiasis occurs in individuals with a hereditary deficiency of the biliary transport protein required for lecithin secretion. Black pigment gallstones occur disproportionately in individuals with high heme turnover. In most cases, however, no risk factor can be identified. o Disorders of hemolysis associated with pigment gallstones include sickle cell anemia, hereditary spherocytosis, and beta-thalassemia.

In cirrhosis, portal hypertension leads to splenomegaly. This, in turn, causes red cell sequestration, leading to a modest increase in hemoglobin turnover. About half of all cirrhotic patients have pigment gallstones. Prerequisites for formation of brown pigment gallstones include colonization of bile with bacteria and intraductal stasis. In the United States, this combination is most often encountered in patients with postsurgical biliary strictures or choledochal cysts. In hepatolithiasis, a condition encountered mainly in ricegrowing regions of East Asia, intraductal formation of brown pigment stones accompanies multiple strictures throughout intrahepatic and extrahepatic bile ducts. This condition causes recurrent cholangitis and predisposes to biliary cirrhosis and cholangiocarcinoma. The etiology is unknown, but liver flukes have been implicated.
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Differential Diagnoses
Appendicitis Gastric Volvulus Cholangiocarcinoma Gastritis, Acute Cholangitis Gastritis, Chronic Cholecystitis Gastroesophageal Reflux Disease Gallbladder Cancer Pancreatic Cancer Gallbladder MucocelePancreatitis, Acute Gallbladder Tumors Pancreatitis, Chronic Gastric Ulcers Peptic Ulcer Disease

Other Problems to Be Considered
Gallbladder gangrene

Workup
Laboratory Studies
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Patients with uncomplicated cholelithiasis or simple biliary colic typically have normal laboratory test results. Acute cholecystitis is associated with polymorphonuclear leukocytosis. In severe cases, mild elevations of liver enzymes may be caused by inflammatory injury of the adjacent liver. Choledocholithiasis with acute common bile duct obstruction initially produces an acute increase in the level of liver transaminases (alanine and aspartate aminotransferases), followed within hours by a rising serum bilirubin level. If obstruction persists, a progressive decline in the level of transaminases with rising alkaline phosphatase and bilirubin levels may be noted over several days. Concurrent obstruction of the pancreatic duct by a stone in the ampulla of Vater may be accompanied by increases in circulating lipase and amylase levels.

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In patients with suspected gallstone complications, blood tests should include a complete blood cell (CBC) count with differential, liver function panel, and amylase and lipase. Repeated testing over hours to days may be useful in evaluating patients with gallstone complications. Improvement of the levels of bilirubin and liver enzymes may indicate spontaneous passage of an obstructing stone. Conversely, rising levels of bilirubin and transaminases with progression of leukocytosis in the face of antibiotic therapy may indicate ascending cholangitis with need for urgent intervention.

Imaging Studies

Upright and supine abdominal radiographs are occasionally helpful in establishing a diagnosis of gallstone disease. o Black pigment or mixed gallstones may contain sufficient calcium to appear radiopaque on plain x-ray films. The finding of air in the bile ducts on plain x-ray films may indicate development of a choledochoenteric fistula or ascending cholangitis with gas-forming organisms. Calcification in the gallbladder wall (the so called porcelain gallbladder) is indicative of severe chronic cholecystitis. o The main role of plain x-ray films in evaluating patients with suspected gallstone disease is to exclude other causes of acute abdominal pain, such as intestinal obstruction, visceral perforation, renal stones, or chronic calcific pancreatitis. Ultrasonography is the most sensitive, specific, noninvasive, and inexpensive test for the detection of gallstones. o Gallstones appear as echogenic foci in the gallbladder. They move freely with positional changes and cast an acoustic shadow. o In acute cholecystitis, ultrasonography may demonstrate edema of the gallbladder wall and pericholecystic fluid. Ultrasonography is also helpful in cases of suspected acute cholecystitis to exclude hepatic abscesses and other liver parenchymal processes. o Routine ultrasonography is less effective for diagnosing stones in the common bile duct, because the distal bile duct passes behind the duodenum and is hidden from view by intestinal gas. Dilatation of the common bile duct on ultrasonographic images is an indirect indicator of bile duct obstruction but may be absent if the obstruction is of recent onset. Computed tomography (CT) scanning is more expensive and less sensitive than ultrasonography for the detection of gallbladder stones. CT scanning is often used in the workup of abdominal pain, as it provides excellent images of all the abdominal viscera. CT scanning is superior to ultrasonography for the demonstration of gallstones in the distal common bile duct. Magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreatography (MRCP) has emerged as an excellent imaging study for noninvasive identification of gallstones anywhere in the biliary tract, including

the common bile duct (see image below). Because of its cost and the need for sophisticated equipment and software, it is usually reserved for cases in which choledocholithiasis is suspected.

Magnetic resonance cholangiopancreatography (MRCP) showing 5 gallstones in the common bile duct (arrows). In this image, bile in the duct appears white; stones appear as dark-filling defects. Similar images can be obtained by taking plain radiographs after injection of radiocontrast material in the common bile duct, either endoscopically (endoscopic retrograde cholangiography) or percutaneously under fluoroscopic guidance (percutaneous transhepatic cholangiography), but these approaches are more invasive. [ CLOSE WINDOW ]

Magnetic resonance cholangiopancreatography (MRCP) showing 5 gallstones in the common bile duct (arrows). In this image, bile in the duct appears white; stones appear as dark-filling defects. Similar images can be obtained by taking plain radiographs after injection of radiocontrast material in the common bile duct, either endoscopically (endoscopic retrograde cholangiography) or percutaneously under fluoroscopic guidance (percutaneous transhepatic cholangiography), but these approaches are more invasive.

Technetium-99m (99m Tc) hepatoiminodiacetic acid (HIDA) scintigraphy is occasionally useful in the differential diagnosis of acute abdominal pain. HIDA is normally taken up by the liver and excreted into bile, where it fills the gallbladder and can be detected with a gamma camera. Failure of HIDA to fill the gallbladder, while flowing freely into the duodenum, is indicative of cystic duct obstruction. A nonvisualizing gallbladder on a HIDA scan in a patient with abdominal pain supports a diagnosis of acute cholecystitis.

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Endoscopic retrograde cholangiopancreatography (ERCP) permits x-ray imaging of the bile ducts. In this procedure, an endoscope is passed into the duodenum and the papilla of Vater is cannulated. Radiopaque liquid contrast is injected into the biliary ducts, providing excellent contrast on x-ray images. Stones in bile appear as filling defects in the opacified ducts. Currently, ERCP is usually performed in conjunction with endoscopic retrograde sphincterotomy and gallstone extraction. Endoscopic ultrasound (EUS) is also an accurate and relatively noninvasive technique to identify stones in the distal common bile duct. Laparoscopic ultrasound has shown some promise as a primary method for bile duct imaging during laparoscopic cholecystectomy.5 Yao et al were able to evaluate the common bile duct with laparoscopic ultrasound during laparoscopic cholecystectomy in 112 of 115 patients (97.4%) with cholelithiasis. In patients who were categorized preoperatively as having a low probability of bile duct stones, the occurrence rate of stones was found to be 7%; in those who were preoperatively assessed as having an intermediate probability of such stones, the occurrence rate was 36.4%; and in those who were rated with the highest probability of bile duct stones, the occurrence rate was 78.9%.5 The investigators suggested that as experience increases with laparoscopic ultrasound, this method may become routine for evaluating the bile duct during laparoscopic cholecystectomy. In addition, Yao et al advised mandatory aggressive preoperative evaluation of the common bile duct in those who are suspected to have an intermediate or high risk of having choledocholithiasis.5

Treatment
Medical Care
The treatment of gallstones depends upon the stage of disease. Ideally, interventions in the lithogenic state could prevent gallstone formation, although, currently, this option is limited to a few special circumstances. Asymptomatic gallstones may be managed expectantly. Once gallstones become symptomatic, definitive surgical intervention with cholecystectomy is usually indicated, although, in some cases, medical dissolution may be considered. Additional interventions may be of value to address acute complications of gallstones, especially in patients who are too sick to tolerate cholecystectomy, and to clear stones from the common bile duct.

Ursodeoxycholic acid (ursodiol) o Ursodeoxycholic acid is a natural bile salt of bears. It is a weak detergent. o In humans, long-term administration of ursodeoxycholic acid reduces cholesterol saturation of bile, both by reducing liver cholesterol secretion and by reducing the detergent effect of bile salts in the gallbladder (thereby preserving vesicles that have a high cholesterol carrying capacity). Desaturation of bile prevents crystals from forming and, in fact, may allow gradual extraction of cholesterol from existing stones. o Ursodeoxycholic acid can be used in 2 ways, as follows:

Ursodeoxycholic acid treatment can prevent gallstone formation. This has been demonstrated in the setting of rapid weight loss caused by very low-calorie diets or by bariatric surgery, which are associated with a high risk of new cholesterol gallstones (20-30% within 4 mo). Administration of ursodeoxycholic acid at a dose of 600 mg daily for 16 weeks reduces the incidence of gallstones by 80% in this setting. In patients with established cholesterol gallstones, treatment with ursodeoxycholic acid at a dose of 12-15 mg/kg daily may result in gradual gallstone dissolution. This intervention typically requires 6-18 months and is successful only with small, purely cholesterol stones. Patients remain at risk for gallstone complications until dissolution is completed. Dissolution fails in many cases. Moreover, after discontinuation of treatment, most patients will form new gallstones over the subsequent 5-10 years.

Surgical Care
Removal of the gallbladder (cholecystectomy) is the treatment of choice for symptomatic cholelithiasis. In some cases of gallbladder empyema, temporary drainage of pus from the gallbladder (cholecystostomy) may be preferred to allow stabilization and to permit later cholecystectomy under elective circumstances. At the time of cholecystectomy, the surgeon can explore the common bile duct and remove common bile duct stones. Alternatively, the surgeon can create a fistula between the distal bile duct and the adjacent duodenum (choledochoduodenostomy), allowing stones to pass harmlessly into the intestine. If surgical removal of common bile duct stones is not immediately feasible, endoscopy can be used to extract common bile duct stones via a small incision in the papilla of Vater (endoscopic sphincterotomy). This approach is especially useful in patients who are critically ill with ascending cholangitis, but it may also be used to remove common bile duct stones inadvertently left behind during previous cholecystectomy.

Cholecystectomy: The first cholecystectomy was performed in the late 1800s. The open approach via subcostal incision pioneered by Langenbuch remained the standard until the late 1980s, when laparoscopic cholecystectomy was introduced.6,7 Laparoscopic cholecystectomy was the vanguard of the minimally invasive revolution, which has affected all areas of modern surgical practice. Currently, open cholecystomy is mainly reserved for special situations. o The traditional open approach to cholecystectomy employed a large, right subcostal incision. In contrast, laparoscopic cholecystectomy employs 4 very small incisions. Recovery time and postoperative pain are diminished markedly by the laparoscopic approach. Currently, the procedure is commonly performed in an outpatient setting. By reducing inpatient stay and time lost from work, the laparoscopic approach has also reduced the cost of cholecystectomy.

The most dreaded and morbid complication of cholecystectomy is damage to the common bile duct. Bile duct injuries increased in incidence with the advent of laparoscopic cholecystectomy, but the incidence of this complication has since declined as experience and training in minimally invasive surgery improve. o Cholecystectomy is generally indicated in patients who have experienced symptoms or complications of gallstones, unless the patient's age and general health make the risk of surgery prohibitive. o Because the natural history of gallstones is generally benign, cholecystectomy is not required for patients with asymptomatic gallstones. However, cholecystectomy for asymptomatic gallstones may be indicated under certain circumstances. These circumstances may include:  Patients with large gallstones greater than 2 cm in diameter  Patients with nonfunctional or calcified (porcelain) gallbladder observed on imaging studies and who are at high risk of gallbladder carcinoma  Patients with spinal cord injuries or sensory neuropathies affecting the abdomen  Patients with sickle cell anemia in whom the distinction between painful crisis and cholecystitis may be difficult In patients who are critically ill with gallbladder empyema and sepsis, cholecystectomy can be treacherous. In this circumstance, the surgeon may elect to perform cholecystostomy, a minimal procedure involving placement of a drainage tube in the gallbladder. This usually results in clinical improvement. Once the patient stabilizes, definitive cholecystectomy can be performed under elective circumstance. Cholecystostomy also can be performed in some cases by invasive radiologists under CT-scan guidance. This approach eliminates the need for anesthesia and is especially appealing in a patient who is clinically unstable. In patients with gallbladder stones who are suspected to have concurrent common bile duct stones, the surgeon can perform intraoperative cholangiography at the time of cholecystectomy. The common bile duct can be explored using a choledochoscope. If common duct stones are found, they can usually be extracted intraoperatively. Endoscopic retrograde sphincterotomy is a medical procedure used to remove gallstones from the common bile duct. The endoscopist cannulates the bile duct via the papilla of Vater. Using an electrocautery sphincterotome, an incision measuring approximately 1 cm is made through the sphincter of Oddi and the intraduodenal portion of the common bile duct, creating an opening through which stones can be extracted. Endoscopic retrograde sphincterotomy is useful in several circumstances, as follows: o Achieving biliary drainage in the patient with ascending cholangitis caused by impaction of a gallstone in the ampulla of Vater o Preoperative clearing of stones from the common bile duct to eliminate the need for intraoperative common bile duct exploration, especially in
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situations where the surgeon's expertise in laparoscopic bile duct exploration is limited or the patient's anesthesia risk is high Preventing recurrence of acute gallstone pancreatitis or other complications of choledocholithiasis in patients who are too sick at present to undergo elective cholecystectomy or whose long-term prognosis is poor

Consultations
Patients with asymptomatic gallstones can be managed expectantly.

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Patients who have experienced an episode of typical biliary colic or a complication of gallstones should be referred to a general surgeon with experience in laparoscopic cholecystectomy. If symptoms are atypical, consultation with a general gastroenterologist may be appropriate. A gastroenterologist specializing in biliary endoscopy should be consulted if endoscopic retrograde sphincterotomy may be required.

Diet
Little evidence suggests that dietary composition affects the natural history of gallstone disease in humans. Obese patients who undertake aggressive weight-loss programs or undergo bariatric surgery are at risk to develop gallstones; short-term prophylaxis with ursodeoxycholic acid should be considered.

Activity
Regular exercise may reduce the frequency of cholecystectomy.

Cholelithiasis: Follow-up
Author: Douglas M Heuman, MD, FACP, FACG, AGAF, Chief of Hepatology, Hunter Holmes McGuire Department of Veterans Affairs Medical Center; Professor, Department of Internal Medicine, Division of Gastroenterology, Virginia Commonwealth University School of Medicine Coauthor(s): Anastasios A Mihas, MD, DMSc, FACP, FACG, Professor, Department of Medicine, Division of Gastroenterology, Virginia Commonwealth University School of Medicine; Consulting Staff, Virginia Commonwealth University Hospitals and Clinics; Chief of GI Clinical Research, Director of GI Outpatient Service, Associate Director of Hepatology, Hunter Holmes McGuire Veterans Affairs Medical Center; Jeff Allen, MD, Assistant Professor, Department of Surgery, University of Louisville Contributor Information and Disclosures Updated: Mar 17, 2010

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Follow-up
Further Outpatient Care

Following cholecystectomy, about 5-10% of patients develop chronic diarrhea. This is usually attributed to bile salts. The frequency of enterohepatic circulation of bile salts increases after the gallbladder is removed, resulting in more bile salt reaching the colon. In the colon, bile salts stimulate mucosal secretion of salt and water. Postcholecystectomy diarrhea is usually mild and can be managed with occasional use of over-the-counter antidiarrheal agents, such as loperamide. More frequent diarrhea can be treated with daily administration of a bile acid-binding resin (eg, colestipol, cholestyramine, colesevelam). Following cholecystectomy, a few individuals experience recurrent pain resembling biliary colic. The term postcholecystectomy syndrome is sometimes used for this condition. o Many patients with postcholecystectomy syndrome have long-term functional pain that was originally misdiagnosed as being of biliary origin. Persistence of symptoms following cholecystectomy is unsurprising. Diagnostic and therapeutic efforts should be directed at the true cause. o Some individuals with postcholecystectomy syndrome have an underlying motility disorder of the sphincter of Oddi, termed biliary dyskinesia, in which the sphincter fails to relax normally following ingestion of a meal. The diagnosis can be established in specialized centers by endoscopic biliary manometry. In established cases of biliary dyskinesia, endoscopic retrograde sphincterotomy is usually effective in relieving the symptoms.

Patient Education

Patients with asymptomatic gallstones should be educated to recognize and report the symptoms of biliary colic and acute pancreatitis. o Alarm symptoms include persistent epigastric pain lasting for greater than 20 minutes, especially if accompanied by nausea, vomiting, or fever. o If pain is severe or persists for more than an hour, the patient should seek immediate medical attention. For excellent patient education resources, visit eMedicine's Liver, Gallbladder, and Pancreas Center and Cholesterol Center. Also, see eMedicine's patient education article Gallstones.

Miscellaneous
Medicolegal Pitfalls
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The major legal liability in the treatment of gallstones rests with the surgeon and interventional endoscopist. Lawsuits against both surgeons and endoscopists have increased since the advent of laparoscopic cholecystectomy. Specific issues for the surgeon include common bile duct injury, trocar-induced bowel damage, and lost stones. o During laparoscopic cholecystectomy, a surgeon must retrieve stones that might escape through a perforated gallbladder. Conversion to an open procedure might be required in certain cases. o In patients in whom gallstones have been lost in the peritoneal cavity, the current recommendation is follow-up with ultrasonographic examinations for 12 months. Most of the complications (usually abscess formation around the stone) occur within this time frame. Common bile duct injury is a recognized complication of cholecystectomy. However, in the legal community, it is often treated as medical malpractice. o A large proportion of lawsuits involving iatrogenic common bile duct injury are resolved in favor of plaintiffs by verdict or by settlement. o Routine cholangiography is only of minimal help in preventing common bile duct injury. However, good evidence indicates that it leads to intraoperative detection of such injuries. o When the anatomy of the biliary tree is uncertain, it is often prudent to convert the procedure to open cholecystectomy.

Cholelithiasis: Multimedia
Author: Douglas M Heuman, MD, FACP, FACG, AGAF, Chief of Hepatology, Hunter Holmes McGuire Department of Veterans Affairs Medical Center; Professor, Department of Internal Medicine, Division of Gastroenterology, Virginia Commonwealth University School of Medicine Coauthor(s): Anastasios A Mihas, MD, DMSc, FACP, FACG, Professor, Department of Medicine, Division of Gastroenterology, Virginia Commonwealth University School of Medicine; Consulting Staff, Virginia Commonwealth University Hospitals and Clinics;

Chief of GI Clinical Research, Director of GI Outpatient Service, Associate Director of Hepatology, Hunter Holmes McGuire Veterans Affairs Medical Center; Jeff Allen, MD, Assistant Professor, Department of Surgery, University of Louisville Contributor Information and Disclosures Updated: Mar 17, 2010
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Multimedia
Media file 1: Cholelithiasis. A gallbladder filled with gallstones (examined extracorporally after laparoscopic cholecystectomy [LC]).

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Cholelithiasis. A gallbladder filled with gallstones (examined extracorporally after laparoscopic cholecystectomy [LC]). Media file 2: Magnetic resonance cholangiopancreatography (MRCP) showing 5 gallstones in the common bile duct (arrows). In this image, bile in the duct appears white; stones appear as dark-filling defects. Similar images can be obtained by taking plain radiographs after injection of radiocontrast material in the common bile duct, either endoscopically (endoscopic retrograde cholangiography) or percutaneously under fluoroscopic guidance (percutaneous transhepatic cholangiography), but these approaches are more invasive.

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