Gallstones | Gallbladder | Bile


Mitchell Conn Educational Goals By the end of this lecture you should be familiar with: 1. Pathogenesis of gallstones. 2. Clinical manifestations of gallstones. 3. Approach to the diagnosis of gallstones and their related morbidity. 4. Treatment modalities for gallstone disease. Gallstones Gallstones are a major cause of morbidity worldwide. In the United States over 10% of the total population have gallstones. Each year 1,000,000 new patients are diagnosed. Performance of 500,000 cholecystectomies leads to an annual expense of more than $5 billion in direct costs. Gallstone prevalence varies with age, sex and ethnic group. Ultrasound surveys show a female: male ratio of 2:1 in the younger population and an increasing prevalence in both sexes with age. After the age of 60, 10-15% men and 20-40% women have gallstones. Childbearing, estrogenreplacement therapy, and oral contraceptives increase the risk of developing gallstones. Gallstone prevalence is especially high in certain populations and regions of the world. Some of the highest incidence of gallstone disease is seen in the Scandinavian countries, Chile and among Native Americans. Populations at low risk are sub-Saharan Africa and Asia. AfricanAmericans have a lower prevalence than whites. Within a given population first degree relatives of persons with gallstones have a 4.5 times greater likelihood to develop gallstones than are matched controls, suggesting a genetic prevalence. The incidence is higher in markedly obese individuals and in those who lose weight rapidly. Gallstones are more frequent among patients with certain diseases such as: regional enteritis (Crohn's disease), cirrhosis of the liver and chronic hemolytic conditions. While they are widely prevalent, gallstones are asymptomatic in the majority of cases. The management of gallstone disease has evolved considerably during the past decade: it is now generally agreed that in most situations patients with gallstones require no treatment until they become symptomatic. Pathogenesis of Gallstones Gallstones are made mainly of cholesterol, bilirubin and calcium salts, with smaller amounts of protein and other materials. In Western Countries essentially all gallstones, whether cholesterol or pigmented, arise in the gallbladder, while in Asia a significant fraction of pigmented stones originate in the bile ducts. In Western Countries cholesterol is the principal constituent of more than three quarters of gallstones. In the simplest sense, cholesterol gallstones form when the cholesterol concentration in bile exceeds the ability of bile to hold cholesterol in solution. Noncholesterol stones are categorized as black or brown pigment stones, consisting of calcium salts of bilirubin. In normal individuals only about 1% the bilirubin in gallbladder bile is unconjugated. When the percentage of unconjugated bilirubin increases so does the risk of developing bilirubin gallstones. 1. Black pigment stones (bilirubin stones) a. Consist of polymers of calcium bilirubinate, with large amounts of mucoprotein. b. Usually contain less than 10% cholesterol. c. Contain 30-60% unconjugated bilirubin by weight. Unconjugated bilirubin is not water soluble, while conjugated bilirubin is water-soluble. d. 50% are radiopaque, 50% are radiolucent (stones that are more than 4% calcium by weight are radiopaque). e. Are common in patients with cirrhosis and chronic hemolytic conditions, such as the thalassemias and possibly sickle cell anemia, in which bilirubin excretion is increased. 2. Brown pigment stones

cholesterol. when incubated in vitro. d. which hydrolyze glucuronic acid from conjugated bilirubin. b. HMG-CoA reductase. and the formation of gallstones in some patients with a lean body mass. 125 . Almost all cholesterol stones are radiolucent. Are usually associated with biliary infection. such as: a. 75-80% of gallstones in this country are classified as cholesterol (non-pigmented) stones. Nucleation promoters: Even when supersaturated with cholesterol. Bacteria in the biliary system release glucuronidases. Thus. but new synthesis of bile acids by the liver usually suffices to compensate for the losses. b. Impaired bile salt return: Seen with ileal disease (Crohn's). which are much larger than micelles and have phospholipid bilayers without bile salts. Cholesterol is the major component (usually greater than 70% by weight). The resulting unconjugated bilirubin precipitating as its calcium salt. c. is stimulated by insulin and food intake. Cholesterol stones a. both increased in obesity. precipitation of cholesterol follows saturation. lecithin. Nucleation: The next step in cholesterol gallstone formation is nucleation of cholesterol into crystals. with variable amounts of protein and cholesterol. followed by agglomeration of crystals and growth of the microlith into macroscopic gallstones. In both experimental models and young people at high risk. The same bile. ileal resection or bypass. Drugs that bind bile acids in the gut. is made soluble through association with bile salts and phospholipids (lecithin). In general the likelihood of stone formation is increased by anything that raises cholesterol level or lowers bile acid levels. fresh bile from subjects without gallstones rarely contains cholesterol crystals. Native American ethnic group. Are made of calcium salts of unconjugated bilirubin. Stages in Cholesterol Gallstone Formation: The three principal defects involved in gallstone formation are: cholesterol supersaturation. the key regulatory enzyme in bile acid synthesis. an increase in cholesterol. As cholesterol saturation increases more cholesterol is solubilized within vesicles. anything that causes a decrease in bile salts. It has also been shown that most patients with gallstones have a smaller pool of bile acid than matched controls without stones. In unsaturated bile.a. This is associated with estrogen treatment in women. Excessive cholesterol synthesis in the face of a normal bile acid pool. b. d. and cholesterol in the bile. Oversensitive feedback mechanism to turn off cholesterol-7-hydroxylase. In unsaturated bile cholesterol is present predominantly in simple (bile salts only) and mixed (bile salts and phospholipids) micelles. or a decrease in lecithin will create relative insolubility of cholesterol in solution. c. 2. normally insoluble. 1. the rate-limiting step in cholesterol synthesis. and the incidence of gallstones within a population is correlated with the prevalence of saturated bile. Cholesterol-saturated bile is a prerequisite for the formation of cholesterol gallstones. accelerated nucleation and gallbladder hypomotility. d. Are more prevalent in Asians. Formation of cholesterol saturated bile: The most critical factor is the ratio of cholesterol/bile acids. such as cholestyramine could also theoretically cause this problem. Combination of mechanisms: endogenous and exogenous estrogens appear to both increase cholesterol secretion and decrease chenodeoxycholate secretion. forms crystals very slowly (up to 15 days). associated with decreased secretory IgA 3. The solubility of cholesterol is determined primarily by the relative proportions of bile acids. Are usually primary bile duct stones c. Evidence for this is the existence of a group of gallstone patients who have a small bile acid pool but normal rate of bile acid synthesis. Bile of patients with cholesterol gallstones.

At least five other proteins have been identified as putative nucleation promoters. Nucleation of cholesterol occurs far more rapidly from gallbladder bile of patients with cholesterol gallstones than from hepatic bile in the same patients. 3. It can be seen on standard ultrasonography of the gallbladder. when incubated. Protein adds strength to the stone. usually does contain cholesterol crystals. The addition of even small amounts of gallbladder bile to the hepatic bile samples causes rapid nucleation. e. Gallstones forming in patients with high spinal cord injury or treated with the somatostatin analog octreotide have been largely associated with impaired gallbladder motility. Cholesterol stones often contain alternating layers of cholesterol crystals and mucoprotein. Mucin glycoprotein is the most important pronucleator identified. 4. is thought to be the usual precursor of gallstones. and its nucleation time. even when hepatic bile samples are supersaturated with cholesterol. or thickened gallbladder mucoprotein with tiny entrapped cholesterol crystals. These observations have led to the isolation of proteins in the gallbladder that promote or retard the nucleation of cholesterol crystals. Sludge can sometimes cause biliary pain. 126 . is much more rapid (mean of 2.on the other hand.g. The antibiotic ceftriaxone can precipitate in the gallbladder and bile ducts as sludge. cholecystitis. Growth: The crystal acquires additional cholesterol to form a visible stone. but may also resolve without treatment. microscopic cholesterol crystals would be regularly ejected from the gallbladder if its contractions were effective enough. or acute pancreatitis. Gallbladder sludge. Pure cholesterol crystals are quite soft. Sludge may also occur in asymptomatic patients with prolonged fasting or TPN. In theory.9 days). This stage of stone formation is largely influenced by gallbladder hypomotility and stasis. Risk Factors Associated with Cholesterol Gallstone Formation Risk Factor Proposed Metabolic Abnormality Older Age Increased cholesterol secretion/decreased bile acid synthesis Female Gender Increased cholesterol secretion/increased intestinal transit time Obesity Increased cholesterol secretion via increased HMG-CoA reductase activity Weight Loss Increased cholesterol secretion/reduced bile acid synthesis/gallbladder hypomotility TPN Increased cholesterol secretion/gallbladder hypomotility Drugs Clofibrate Decreased bile acid concentration by suppression of 7-alpha-hydroxylase Oral contraceptives Increased cholesterol secretion Estrogens Cholesterol hypersecretion/reduced bile acid secretion Progesterones Increased cholesterol secretion Ceftriaxone Precipitation of an insoluble calcium-ceftriaxone salt Octreotide Decreased gallbladder motility Genetics Native Americans Increased cholesterol synthesis/reduced bile salt synthesis Scandinavians Increased cholesterol secretion Ileal Diseases Hyposecretion of bile salts from diminished bile salt pool Lipid Profile Decreased HDL Increased activity of HMG-CoA reductase High Triglycerides Increased activity of HMG-CoA reductase Apolipoprotein E-4 Proposed pronucleator Bile Duct Stones Primary bile duct stones are stones formed in the biliary tree as the result of bile stasis. spinal cord injuries and prolonged treatment with octreotide.

either having migrated out of the gallbladder or having formed concomitantly in the bile ducts. around foreign material such as a suture. Approximately 20% of these patients will become symptomatic over a 10-15 year period. biliary pain begins suddenly and persists for 1 to 3 hours. Acute inflammation of the gallbladder is caused by calculous obstruction of the cystic duct in >90% of cases (some patients may present with acalculous cholecystitis). and patients with gallstones and calcification of the gallbladder wall (porcelain gallbladder).e. or chemically by release of lysolecithin by phospholipase activity. and black pigment in ~20% of cases. and often radiates to the infrascapular area or right scapula. results in acute cholecystitis. Biliary colic is a term that has persisted despite the understanding that biliary disease does not involve the colon or colic. Bacterial infection is not thought to be important in the pathogenesis of either type of secondary stones. Moving about does not intensify the pain. The frequency of episodes may vary from weeks to years. or in association with infection. Acute cholecystitis. predominantly cholesterol in ~80%. enteric organisms have been cultured from 75% of patients with acute cholecystitis. deconjugated by the 127 . It is thought that sudden obstruction of the cystic duct by a calculus produces increased intraluminal pressure and distention of the gallbladder. and are composed predominantly of calcium bilirubinate and minor amounts of cholesterol or fatty acids. and a residual aching discomfort may persist for a day or so. Bile acids. Results of hepatic chemistry determinations usually are normal. leading to a visceral-type pain. Recurrent pain attacks occur in up to 50% of patients and the risk of a more significant complication is estimated to be 1-2% a year. muddy stones that can reach large dimensions. it is felt as a steady. Recurrent biliary pain (or colic) is the most common indication for treatment. Their matrix reflects the composition of gallbladder stones. A narcotic is often required for analgesia.above a stricture. Discrete attacks may be precipitated by meals. The inflammation is thought to be caused mechanically by increased intraluminal pressure and ischemia. The term "colic" is actually misleading. which is considered a premalignant condition. rather. They are often earthy. Usually the pain is felt in the epigastrium or right upper quadrant. and the patient's general health. in contrast to the transient obstruction that produces biliary pain. i. Bacterial infection may supervene. attempting but failing to find a position that affords relief. The pain may subside gradually or rapidly after a stone becomes disimpacted or passes through the cystic duct. Nausea is common and vomiting occurs occasionally. Clinical manifestations of gallstones Asymptomatic gallstones: 80% of people harboring gallstones are asymptomatic at any given point in time. These stones do not dissolve well in lipid solvents and may be found in the intrahepatic or extrahepatic bile ducts. In fact. Characteristically. Asymptomatic gallstones should be managed expectantly in the majority of patients. as the pain does not wax and wane. most patients are restless and pace the floor. severe aching or pressure-type sensation. Secondary bile duct stones are found in the bile ducts in association with gallbladder stones. and elective cholecystectomy is much safer than urgent operations in this group). patients in remote locations where urgent medical care is not possible. Biliary Colic is the most common presenting symptom of cholelithiasis. or may occur at any time of the day or night. but may be associated with chronic hemolysis or cirrhosis. Symptomatic gallstones need to be treated in a time frame that is appropriate for the seriousness of the clinical presentation. Persistent obstruction of the cystic duct. There are some exceptions such as patients with sickle cell anemia (symptoms of gallstones may mimic those of sickle cell crisis. although it may last as little as 15 minutes or as long as 6 hours. Black pigment stones are usually idiopathic.

bacteria. Hepatomegaly occurs in 25% of patients. continuous or intermittent. The gallbladder is generally enlarged. Deep inspiration during palpation of the right upper quadrant produces increased tenderness and inspiratory arrest (Murphy's sign). the inflammation progresses to necrosis. Splenomegaly may be found when pigment stones are associated with hemolytic disease. Cholecystectomy is the appropriate treatment for patients with acute cholecystitis. and antibiotics alone are not sufficient to treat the infection in the setting of persistent biliary obstruction. and shaking chills do not occur. In the remaining 25%. alkaline phosphatase (usually to less than twice normal) in 31% and transaminases (usually to less than five times normal) in 41% of patients. and therefore are febrile and dehydrated and may have an ileus in addition to abdominal pain. pulse rate and white blood cell count. an intraluminal gallbladder abscess from persistent complete obstruction of the cystic duct. It is estimated that 30% of patients with acute cholecystitis admitted for cholecystectomy have had no previous symptoms suggestive of cholelithiasis. Nausea is common and vomiting occurs occasionally. most 128 . as operative mortality is exceedingly high in the phase of acute cholangitis. perforation or empyema of the gallbladder unless intervention occurs. In up to 75% of patients with acute cholecystitis. Complications of acute cholecystitis are empyema. Common bile duct obstruction may result. less often. initially for drainage of bile alone. Complications of gallstones: Choledocholithiasis occurs in 20% of patients with gallstones. Patients with concomitant cholangitis (infection of the bile ducts) should undergo initial endoscopic or percutaneous drainage. acute cholecystitis causes a parietal-type epigastric or right upper-quadrant pain that increases with jarring or respiration. Common bile duct stones may cause biliary type pain. signs of peritonitis. Biliary colic may precede or. or rising temperature. often leading to a walled-off abscess. symptoms resolve spontaneously within 72 hours after onset. Approximately 50% have had symptoms of acute cholecystitis for at least 48 hours prior to admission. and may be partial or complete. Unstable patients should be managed percutaneously. In elderly or diabetic patients or in patients treated with corticosteroids for other reasons. In contrast to biliary colic. gallbladder perforation (5%). The patient should initially be stabilized with antibiotics and fluids to reduce anesthesia complications. but the peripheral stigmata of chronic liver disease are absent. also may contribute to the inflammation. hepatic bile flow is suppressed and conjugated bilirubin flows into the blood stream causing jaundice. Local cutaneous hyperesthesia is not uncommon. irrespective of age. cholecystitis recurs in 25% of patients within the first year of follow-up and in 60% of patients within 6 years. Biliary obstruction often leads to ascending cholangitis with aerobic or anaerobic organisms. If common bile duct pressure exceeds 25 cm H2O. but local guarding of the abdomen hinders effective palpation in more than half of the patients.000 to 15. mild signs and symptoms may belie the severity of the inflammation.000/mm3 with a shift to the left is usual. A leukocyte count of 10. In a large series of patients with acute cholecystitis elevation of the following values were reported: serum bilirubin (almost never more than 5 mg/100 ml in the absence of concomitant bile duct obstruction) in 37%. after the stone presumably disimpacts or passes through the cystic duct. later for elective stone extraction. Clinical indications of progression are persistent symptoms. When surgery is not performed. The patient prefers to remain motionless. accompany or follow acute cholecystitis. The fever usually is low grade (averaging about 38o C). Tenderness in the scapular area (Boas' sign) is less common. Values typically returned to normal within 1 week after resolution of symptoms.

etc. In addition to the presence of gallstones. It has become useful as a non-invasive tool to detect common bile duct stones. though the technique has been "modernized" with a laparoscopic approach. Removal of the gallbladder is a desirable treatment endpoint to prevent gallstone recurrence. Cohort studies suggest that patients with symptomatic stones develop gallbladder cancer at higher rates than do patients with asymptomatic stones. New treatment modalities have emerged and have been replaced. and of gallbladder muscular function (gallbladder ejection fraction can be measured after CCK injection). and 1% of patients with gallstones at autopsy have gallbladder cancer.relies upon hepatic uptake and excretion into bile of an IV radioactive compound. resulting in choledocho-duodenal fistula. discussed later). Acute pancreatitis may occur as result of ampullary obstruction by a gallstone (30%-75% of patients with acute pancreatitis have gallstones). In severely ill patients CT can detect complications of gallstones such as emphysematous cholecystitis. can be done even in presence of jaundice. or papillary stenosis. Plain abdominal x-ray .frequently E. Cholecystectomy remains the mainstay of therapy. Large stones impacting at the level of the ileocecal valve may cause Gallstone ileus. Gallbladder cancer rates are about 3-5% in Native Americans. pericholecystic fluid). such as biliary strictures. About 80% of patients with gallbladder cancer have stones. and improvement of the symptoms. Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) – Both these modalities are not routinely used in the diagnosis of gallstones. perforation of the gallbladder. Pressure and inflammation caused by prolonged stone impaction in the common bile duct may cause the stone to pass. Does not require oral intake. Ultrasonography does not depend on gallbladder function. A gallstone in the cystic duct may obstruct the common bile duct by extrinsic compression. Gallbladder cancer occurs in 50% of patients with a calcified gallbladder wall (porcelain gallbladder).20% of gallstones visualize (>4% calcium by weight) 2. Ultrasonography . Reliable study of obstruction (e. Non-surgical treatment modalities have their best application in patients in whom surgical 129 .as sensitive and specific as oral cholecystography. particularly if they have gallstones. Obstructed common bile duct: no contrast seen in duodenum. and without preparing the patient other than fasting. MRI imaging can produce images of the biliary tree (MRCP) comparable to endoscopic cholangiography (ERCP.). ultrasonography can detect signs of acute cholecystitis (gallbladder wall thickening. Formation of the fistulous tract usually coincides with stone passage. Images of the biliary tree are recorded by a gamma camera.g. Can be performed in patients with acute cholecystitis. presence of stones). but much more direct and commonly performed. Can be done and is diagnostic in patients with acute cholecystitis. through necrotic and softened tissues. coli. 4. Treatment of gallstones may lead to surgical complications. Direct information of gallbladder function can be gained using feeding or cholecystokinin (CCK) injection to provoke gallbladder emptying. or transection of the bile ducts. CT can only visualize calcified gallstones. obstructed cystic duct: no contrast seen in gallbladder. pancreatitis or abscesses. into the duodenum. Treatment modalities for gallstone disease Progress in the treatment of gallstone disease has been rapid during the past decade. Hepatobiliary scan (HIDA) . Recurrent passage of stones through the ampullary orifice may cause inflammatory changes resulting in papillary stenosis. Patients with the finding of porcelain gallbladder should undergo cholecystectomy. Diagnosis 1. bile leaks. Gallbladder cancer accounts for one third to one half of gallstone related death in USA. and give information regarding the bile ducts (dilation. causing Mirizzi's syndrome. 3.

and cost of each available treatment is essential for optimal management. laparoscopic cholecystectomy requires more O. If the bile duct stones are known to be present before cholecystectomy. and perhaps higher surgical skill. ERCP with sphincterotomy is the treatment of choice for retained or new bile duct stones after cholecystectomy. Complications may be slightly more frequent with the laparoscopic operation. Dissolution Therapy 130 . Laparoscopic cholecystectomy has rapidly become popular as definitive therapy for gallstones. This procedure is today routinely performed in association with laparoscopic cholecystectomy to treat concomitant gallbladder and bile duct stones (see above). and anatomy of the cystic duct). and tend to occur early in the surgeon's laparoscopic experience. or with the use of electrohydraulic or laser energy conveyed through probes. or to complete the cholecystectomy laparoscopically and use postoperative ERCP to clear the bile ducts. or the patient can be managed directly with open cholecystectomy and common bile exploration. When the surgeon detects bile duct stones by cholangiography during cholecystectomy. and still avoid general anesthesia. unfavorable anatomy. laparoscopic cholecystectomy has been performed successfully also in patients with acute cholecystitis. Patients are usually discharged the day after the operation. Patients who will later develop cholecystitis can be treated percutaneously. time. Laparoscopic removal of common bile duct stones through the cystic duct is available at many centers. and surgical scars are less visible. Knowledge of specific endpoints. and perform common bile duct exploration. Stones can consequently be removed by means of balloons or baskets. Compared to open cholecystectomy. Endoscopic Therapy. The surgical alternatives are to convert the operation to open. their clearance with ERCP is usually performed preoperatively. Very large bile duct stones. Surgical instruments are inserted through stab wounds in the upper abdomen. Needle tracts can de dilated to allow passage of thin cholangioscopes with operating channels. size of the stones. This modern surgical technique allows removal of the gallbladder via a laparoscope inserted through a small incision in the umbilicus.R. efficacy. previously only amenable to surgical removal. Combined efforts with gastrointestinal endoscopists have been used to avoid operations in poor surgical candidates. and laparoscopic cholecystectomy is scheduled to follow. If stones are found. traditionally offered by Interventional radiologists. is used to treat both gallbladder and bile duct stones. or a complication may require conversion of planned laparoscopic cholecystectomy into an open operation. It requires added surgical skill and significant additional anesthesia time. it allows fragmentation or dissolution of stones. Percutaneous Therapy. availability of equipment necessary. he or she may attempt to remove them laparoscopically through the cystic duct if possible (depending on training of the would not be prudent. Extensive abdominal scarring. risk. because of age or concomitant medical illness. Laparoscopic cholecystectomy. ERCP/sphincterotomy not followed by cholecystectomy is used to treat bile duct stones in patients who are poor risks for surgery and who have concomitant gallbladder stones without cholecystitis. In addition to drainage of infected bile. Percutaneous access. it requires reduced hospital stay and recuperation time. Compared to the open operation. an electrocautery cutting instrument can be inserted into the ampulla to enlarge the opening of the bile duct into the duodenum (sphincterotomy). and are able to return to work in only 1-2 weeks. Initially used only as an elective operation in patients with biliary colic. Postoperative pain is significantly reduced. Endoscopic retrograde cholangiopancreatography (ERCP) has significantly reduced the need for surgical exploration in patients with common bile duct stones. can be fragmented to facilitate endoscopic extraction either mechanically with wire baskets.

but caused diarrhea in almost half and abnormal aminotransferase levels in a third. Nucleation and growth of cholesterol crystals: kinetic determinants in supersaturated native bile. Ursodiol also prolongs the nucleation time in the gallbladder bile by shifting cholesterol from vesicles to micelles. Johnston. 6. 1993. Oral cholecystography can assess both gallstone composition and cystic duct patency. and spillage into the duodenum causes severe inflammation. 2.119:606-619. but leave the gallbladder in place. is instilled into the gallbladder until dissolution is complete. et al. and its epimere ursodeoxycholic acid (Ursodiol. It causes a competitive blockade of bile acid reabsorption in the terminal ileum. Chapter 55. and appear to respond well to dissolution therapy. in: Sleisenger and Fordtran’s. Gallstones that form after dissolution seem to cause symptoms less often than original gallstones (10-20% of subjects). without inhibiting synthesis of endogenous bile acids. Ursodiol should not be used for calcified gallstones or if the cystic duct is obstructed. Gastroenterol Clin North Am 1991. Prevention of gallstone recurrence with oral bile acids is effective. WB Saunders Philadelphia. Strasberg et al . 6th Edition. The potential for recurrence should not preclude dissolution in poor surgical candidates with limited life expectancy. Ursodiol reduces the synthesis of cholesterol in the liver and its secretion into bile. LaMorte. Its multiple effects cause cholesterol desaturation in bile without raising serum cholesterol levels. Gastroenterology 1990. Treatment of gallstones. but expensive. References: 1. Contact Agents: Contact gallstone dissolution requires percutaneous or endoscopic access to the gallbladder. is flammable. The probability of forming a new stone is considerably lower in the 10-15% of patients with a single initial cholesterol gallstone.20:67-84 5. Role of the gallbladder in the pathogenesis of cholesterol gallstones. As for all therapies that eliminate stones. et al. and is the principal bile acid in bears (hence. Bilhartz LE and Horton JD. stones often recur (43% at 4 years. though only 25% of the recurrent stones cause symptoms. 131 . Ursodiol constitutes 1-2% of bile in humans. It has no place in the management of acute cholecystitis. completely dissolved stones in 14. W. Ann Intern Med 1993. and is still considered experimental. 49% at 11 years). Methyl-tert-butyl ether (MTBE). Actigall). the first bile acid to be used in clinical trials. Cholesterol gallstones dissolve at the rate of about 1 mm per month and disappear completely within 6-24 months in 30-50% of patients. High protein and total lipid concentration are associated with reduced metastability of bile in an early stage of cholesterol gallstone formation. 1979. et al. the prefix urso). Success is increased by strict patient selection. Holzbach.98:739-46. MTBE has systemic toxicity. Contact dissolution with MTBE is the most rapid of the non-surgical therapies and can in fact complete gallstone dissolution within 24 hours. N Engl J Med. Ursodeoxycholic acid has greater efficacy and fewer side effects. Gastroenterology 77:580. Pathogenesis and treatment of gallstones. Chenodeoxycholic acid. Chenix) a primary human bile acid. Gallstones will recur in ~50% of the subjects within 5-7 years from successful dissolution. Gallstone Disease and Its Complications. 3.328(6):412-421. 4. reduces biliary output of cholesterol. et al.Oral Agents: Oral intake of chenodeoxycholic acid (Chenodiol. Therapy with bile acids is suitable only for a minority of patients who refuse or are poor risk for surgery. Ransohoff. Gallstone recurrence and prevention: The potential for gallstone recurrence exists in all patients treated with modalities that leave the gallbladder in place.5% patients.W. 1998. This therapy is likely to find its maximal use only in older subjects and poor surgical candidates. the solvent most widely investigated.

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