Gallstones and Gallbladder Disease

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GALLSTONES AND GALLBLADDER DISEASE

WHAT ARE GALLSTONES AND GALLBLADDER DISEASE?

Bile and the Gallbladder

The formation of gallstones is a complex procedure that starts with bile, a fluid composed mostly of water, bile salts, lecithin (a fat known as a phopholipid), and cholesterol. (Most gallstones are formed from cholesterol.)

Bile is first produced by the liver and then secreted through tiny channels that eventually lead into a larger tube called the common bile duct , which leads to the small intestine.
Only a small amount of bile drains directly into the small intestine, however. Most flows into the gallbladder through the cystic duct , which is a side extension off the common duct. (The system of ducts through which bile flows, including the common bile duct is called the biliary tree).
The gallbladder is a four-inch sac with a muscular wall that is located under the liver. Here, most of the fluid (about two to five cups a day) is removed, leaving a few tablespoons of concentrated bile.
Bile is important for the digestion of fat. The gallbladder serves as a reservoir until bile is needed in the small intestine for this function.
A hormone called cholecystokinin is released when food enters the small intestine. Cholecystokinin signals the gallbladder to contract and deliver bile into the intestine.
The force of the contraction propels the bile back down the common bile duct and then into the small intestine, where it emulsifies (breaks down) fatty molecules.
This process allows the emulsified fat as well as fat-absorbable nutrients, including vitamins A, D, E, and K, to enter the blood stream through the intestinal lining.

Formation of Gallstones (Cholelithiasis)

About three-quarters of the gallstones found in the US population are formed from cholesterol. About 15% of gallstones are known as pigment stones. Patients may also have a mixture of pigment and cholesterol gallstones. Gallstones can range from a few millimeters to several centimeters in diameter.

Cholesterol Stones. Cholesterol makes up only five percent of bile. It is not very soluble, however, so in order to remain suspended in fluid, it must be properly balanced with bile salts. If there is an imbalance in bile salts and cholesterol, the following occurs:

The fluid turns to sludge, which consists of a mucus gel containing cholesterol and calcium bilirubinate.
If the process continues, cholesterol crystals form out of the bile solution ( supersaturation) and can eventually form gallstones.
This process is referred to as cholelithiasis. It is very slow and most often painless.

Supersaturation and cholelithiasis can occur as a result of various abnormalities, although the cause is not entirely clear. Events that may promote cholelithiasis include the following:

The liver secretes too much cholesterol into the bile.
The gallbladder has defective emptying mechanisms so that the bile becomes stagnant and sludge forms, eventually forming stones.
The cells lining the gallbladder may lose their capacity to efficiently absorb cholesterol and fat from bile.

Pigment Stones. Pigment stones are composed of calcium bilirubinate, or calcified bilirubin. Bilirubin is a substance normally formed by the breakdown of hemoglobin in the blood and it is excreted in bile. Pigment stones can be black or brown and often form in the gallbladders of people with hemolytic anemia (a relatively rare anemia where red blood cells are destroyed) or cirrhosis.

Effects of Gallstones. Gallstones can cause obstruction at any point along the ducts that carry bile:

In most cases of obstruction, the stones block the cystic duct, which leads from the gallbladder to the common bile duct. This can cause pain ( biliary colic ), infection and inflammation (called cholecystitis), or both.
About 10% of patients with symptomatic gallstones also have stones that pass into and obstruct the common bile duct (called choledocholithiasis).

Gallbladder Diseases without Stones

Gallbladder disease can occur without stones (called acalculous gallbladder disease). [ See Box Gallbladder Disease without Stones.]

GALLBLADDER DISEASE WITHOUT STONES
(A CALCULOUS GALLBLADDER DISEASE)

Gallbladder disease can occur without stones (called acalculous gallbladder disease). It can be acute or chronic.

Acute acalculous gallbladder disease usually occurs in patients who are very ill from other disorders. In such cases, inflammation occurs in the gallbladder, usually from a diminished blood supply or an impairment in the ability of the gallbladder to contract.
Chronic acalculous gallbladder disease (also called biliary dyskinesia) appears to be caused by defects in the gallbladder that impair its ability to contract and release bile.

Diagnosing Chronic Acalculous Gallbladder Disease

Chronic acalculous gallbladder disease is usually diagnosed when a patient complains of gallbladder symptoms but there is no radiologic evidence of stones. (More than half of patients initially diagnosed with this disease however, are eventually shown to have small stones or gallbladder sludge.) The patient is given the hormone cholecystokinin octapeptide (CCK), which induces gallbladder contraction, followed by a radioisotope scan that determines if the gallbladder is emptying correctly. If the gallbladder demonstrates difficulty releasing bile, doctors usually consider the diagnosis confirmed.

Treatment for Chronic Acalculous Gallbladder Disease

Most patients (75% to 90%) diagnosed with chronic acalculous gallbladder disease [ see above ] are relieved of their symptoms by cholecystectomy (removal of the gallbladder). [ See What Are the Surgical Procedures for Gallstones and Gallbladder Disease?, below.] More than half of patients are subsequently shown to have small stones or gallbladder sludge that was not visible on their ultrasounds. A 2001 study indicates that a muscle defect might be the cause of the disease in patients who do not have stones or sludge.

WHAT ARE THE SYMPTOMS OF GALLSTONES AND GALLBLADDER DISEASE?

Most gallstones provoke no symptoms at all. If symptoms do occur, the chance of developing pain is about 2% per year for the first ten years after stone formation, after which the chance for developing symptoms declines. On average, symptoms take about eight years to develop. The reason for the decline in incidence after ten years is not known, although some physicians suggest that "younger," smaller stones may be more likely to cause symptoms than larger ones.

Biliary Pain

The mildest and most common symptom of gallbladder disease is intermittent pain called biliary colic , which occurs either in the mid- or the right portion of the upper abdomen. A typical attack has several features:

Large or fatty meals can precipitate the pain, but it usually occurs several hours after eating and often wakes the patient during the night.
The primary symptom is steady pain on the right side (under the rib cage), which can be quite severe. Changes in position, over-the-counter pain relievers, and passage of gas do not relieve the symptoms.
The patient may experience nausea or vomiting.
Biliary colic typically disappears after one to five hours.

Recurrence is common but attacks can be years apart. In one study, for example, 30% of people who had had one or two attacks, experienced no further biliary pain over the next ten years.

Symptoms of Acute Cholecystitis (Gallbladder Inflammation)

Inflammation and infection in the gallbladder ( acute cholecystitis ) are usually caused by gallstones. (In some cases, it can occur without stones.) The symptoms in either case are similar to those of biliary colic but are more severe and serious. They include the following:

Severe pain and tenderness in the upper right abdomen are the most common. It also may radiate to the back or occur under the shoulder blades. Pain frequently occurs when drawing a breath.
The discomfort is intense and steady and can last for days.
About a third of patients have fever and chills.
Nausea and vomiting may occur.

Anyone who experiences such symptoms should seek medical attention. Acute cholecystitis can progress to gangrene or perforation of the gallbladder if left untreated. (People with diabetes are at particular risk for this complication.)

Symptoms of Chronic Cholecystitis or Dysfunctional Gallbladders

Chronic gallbladder disease ( chronic cholecystitis ) occurs with gallstones and low-grade inflammation. In such cases the gallbladder may become scarred and stiff. Symptoms of chronic gallbladder disease include the following:

Complaints of gas, nausea, and abdominal discomfort after meals are the most common, but they may be vague and indistinguishable from similar complaints in people without gallbladder disease.
A 2000 study reported that chronic diarrhea (four to 10 bowel movements every day for at least three months) may be a common symptom of gallbladder dysfunction.

Symptoms of Common Bile Duct Stones (Choledocholithiasis)

Stones lodged in the common bile duct ( choledocholithiasis) can cause somewhat different symptoms:

If they block the flow of bile, they can cause jaundice (yellowish skin).
If they cause infection in the bile duct (called cholangitis), symptoms may include fever, chills, nausea and vomiting, and severe pain in the upper-right quadrant of the abdomen.
Heartbeat may become rapid and blood pressure may drop abruptly.

As with acute cholecystitis, these are symptoms that indicate an emergency situation.

HOW SERIOUS ARE GALLSTONES AND GALLBLADDER DISEASE?

Asymptomatic gallstones seldom lead to problems. Death from even symptomatic gallstones is very rare, accounting for only 0.2% of annual deaths in the United States. Serious complications are rare and, if they occur, usually develop from stones in the bile duct or after surgery.

Complications of Acute Cholecystitis (Gallbladder Inflammation)

The most serious complication of acute cholecystitis is infection that spreads to other parts of the body ( septicemia). This can be life threatening. Symptoms include fever, rapid heartbeat, fast breathing, and mental confusion.

Among the conditions that can lead to septicemia are the following:

Gangrene or Abscesses. If acute cholecystitis is untreated and becomes very severe, inflammation can cause abscesses or destroy enough tissue in the gallbladder (called necrosis) to lead gangrene.
Perforated Gallbladder. About 1% to 2% of persons with acute cholecystitis have a perforated gallbladder, which is a life-threatening condition. The risk for perforation increases with a condition called emphysematous cholecystitis , in which gas forms in the gallbladder. This condition is most common in people with diabetes.
Empyema. Pus in the gallbladder (called empyema) occurs in 2% to 3% of patients with acute cholecystitis. Abdominal pain is usually severe and is typically present for more than seven days. The physical exam is not distinctive. The condition can be life threatening, particularly if the infection spreads to other parts of the body.

Both perforation and empyema require prompt surgery. This complications can be avoided, however, by seeing a physician as soon as gallbladder symptoms occur.

Complications from Choledocholithiasis (Stones in the Common Bile Duct)

When gallstones lodge in the common bile duct ( choledocholithiasis) instead of the gallbladder, serious complications can occur.

Infection in the Common Bile Duct (Cholangitis). Infection in the common bile duct ( cholangitis) from obstruction is common and serious. Those at highest risk for a poor outlook also have one or more of the following conditions:

Kidney failure.
Liver abscess.
Cirrhosis.
Age over 50 years.

If antibiotics are administered immediately, the infection clears up in 75% of patients. If cholangitis does not improve, the infection may spread and become life threatening. Either surgery or a procedure known as endoscopic sphincterotomy is required to open and drain the ducts.

Pancreatitis. Choledocholithiasis is responsible for most cases of pancreatitis (inflammation of the pancreas), a condition that can be life threatening. The pancreatic duct, which carries digestive enzymes, joins the common bile duct right before it enters the intestine. It is therefore not unusual for stones that pass through or lodge in the lower portion of the common bile duct to obstruct the pancreatic duct.

Gallbladder Cancer and Porcelain Gallbladders

Gallstones are present in about 80% of people with gallbladder cancer. This cancer is very rare, however, even among people with gallstones. The exception is in people with so-called porcelain gallbladders, who have a very high risk for cancer. (In this condition, the gallbladder walls have become so calcified that they look like porcelain on an x-ray.) Whether gallstones themselves cause the cancer, or whether some factor in bile is responsible for both conditions is unknown. One study demonstrated that gallbladder removal reduced the likelihood of bile duct cancer, suggesting that gallstones themselves were responsible.

WHO GETS GALLSTONES AND GALLBLADDER DISEASE?

Between 10% and 20% of all adults over 40 have gallstones. (Only 1% to 3% of the population, however, complains of symptoms during the course of a year.)

Risk Factors in Women

Women are much more likely than men to develop gallstones. They occur in nearly 25% of women in the US by age 60 and up to 50% by age 75. (Again, in most cases they are asymptomatic.) In general, women are probably at increased risk because estrogen stimulates the liver to remove more cholesterol from blood and divert it into the bile.

Pregnancy. Pregnancy increases the risk for gallstones, although they may disappear after delivery. Pregnant women with stones are more likely to have symptoms than nonpregnant women.

Hormone Replacement Therapy. Women taking hormone replacement therapy are at higher risk for gallstones. Estrogen administered through the patch may pose a lower risk than oral estrogen. One study suggested, however, that oral and patch forms of estrogen replacement therapy pose equal risks for cholesterol supersaturation and therefore gallstone formation. In any case, oral estrogen has a greater effect on the liver itself and raises triglycerides, a fatty acid that increases the risk for cholesterol stones. Postmenopausal women at high risk for both gallstones and disorders related to estrogen loss may want to check with their physicians for alternatives to hormone replacement therapy. (There appears to be a very low or no risk with low-dose oral contraceptive in premenopausal women.) [ See the Report #40, Menopause, Estrogen Loss, and Their Treatments. ]

Risk Factors in Men

About 20% of men have gallstones by the time they reach 75 years of age. Because most cases are asymptomatic, however, the rates may be underestimated in elderly men. One study of nursing home residents reported that 66% of the women and 51% of the men had gallstones. Men who have their gallbladders removed, moreover, are more likely to have severe disease and operative complications than women.

Risks in Children

Gallstone disease is relatively rare in children. When they occur they are more likely to be pigmented stones. Girls do not seem to be more at risk than boys are. The following conditions may put children at higher risk:

Spinal injury.
History of abdominal surgery.
Sickle-cell anemia.
Impaired immune systems.
Intravenous nutrition.

Ethnicity

Hispanics and Northern Europeans have a higher risk for gallstones than people of Asian and African descent do. (People of Asian descent who develop gallstones are most likely to have the pigment type.) Native Americans, particularly Pima Indians, are especially prone to developing gallstones. Pima women, in fact, have an 80% chance of developing gallstones during their lives. (It should be noted, however, that the Pima tribe has a very high incidence of obesity and diabetes, which are both related to gallstones.)

Diabetes

People with diabetes are at higher risk for gallstones and have a higher than average risk for acalculous gallbladder disease (without stones). Gallbladder disease may progress more rapidly in patients with diabetes, who tend to suffer worse infections in general.

Obesity and Weight Changes

Obesity. Being overweight is a significant risk factor for gallstones. In such cases, the liver over-produces cholesterol which is delivered into the bile and causes it to become supersaturated. Some evidence suggests that specific dietary factors (saturated fats and refined sugars) are the primary culprit in these cases, although studies are conflicting. Animal studies, however, suggest that obesity itself, not any particular foods, triggers the process leading to cholesterol supersaturation and the formation of stones.

Weight Cycling. Rapid weight loss or cycling (dieting and then putting back weight) further increases cholesterol production in the liver, with resulting supersaturation and risk for gallstones. A 2000 study suggested the following rates for gallstones related to extreme and rapid weight loss:

The risk for gallstones as high as 12% after eight to 16 weeks of restricted calorie diets.
The risk is more than 30% within a year to 18 months after gastric by-pass surgery.

About one-third of gallstone cases in these situations are symptomatic. The risk for gallstones are highest in the following dieters:

Those who lost more than 24% of their initial body weight.
Those who lose more than 1.5 kg (3.3. lb.) a week.
Those on very low-fat, low-calorie diets.

Weight cycling also puts people at risk for gallstones. For example, a 16-year study found that the risk for gallstone surgery was 68% higher for women who lost and then regained more than 20 pounds at least once than in women whose weight remained stable.

Cholesterol and Cholesterol-Lowering Drugs

Gallstone formation does not correlate with overall cholesterol levels, but persons with low HDL cholesterol (the so-called good cholesterol) levels or high triglyceride levels are at increased risk for stones. In fact, the cholesterol- lowering drugs gemfibrozil (Lopid) and clofibrate (Atromid-S) reduce cholesterol levels in the blood by increasing the amount secreted into the bile, thus creating a higher risk for gallstones. (Other cholesterol-lowering agents do not have this effect.) [ See report #23, Cholesterol.]

Other Risk Factors

Prolonged Intravenous Feeding. Prolonged intravenous feeding reduces the flow of bile and increases the risk for gallstones.

Cirrhosis. Cirrhosis poses a major risk for gallstones, particularly pigment gallstones.

Diuretics. In addition to the cholesterol-lowering drugs mentioned above, thiazide diuretics may slightly increase the risk for gallstones.

Blood Disorders. Chronic hemolytic anemia, including sickle cell anemia, increases the risk for pigment gallstones.

HOW CAN GALLSTONES AND GALLBLADDER DISEASE BE PREVENTED?

Dietary Considerations

Dietary Factors. Some studies have suggested that certain dietary factors may be protective:

Everyone should reduce their intake of saturated fats, and especially people at risk for gallbladder disease. Some studies, however, have found an association between a lower risk for gallstones in people who consumed foods containing monounsaturated fats (found in olive and canola oils).
High-intake of fiber has been associated with a lower risk for gallstones.
Lecithin is a fat known as a phospholipid, which is known to help prevent the formation of cholesterol gallstones. Dietary lecithin is available in health food stores and is found in eggs, soybeans, liver, wheat germ, and peanuts. Animal studies have suggested that soy and buckwheat protein may protect against gallstones: in one such study, buckwheat offered more protection than soy. There is no evidence that lecithin supplements or foods containing it can prevent gallstones in humans.
High-intake of sugar has been associated with an increased risk for gallstones.
Alcohol in small amounts (one ounce per day) has been found to reduce the risk in women by 20%. It should be stressed that alcohol is easily abused, and higher amounts may increase the risk of many diseases, including breast cancer, in women.
Ascorbic acid (vitamin C) appears to help break cholesterol down in bile. Vitamin C deficiencies have been associated with a higher risk for gallstones. One 2000 study, which confirmed some previous ones, reported that supplements were associated with a reduced risk for gallbladder disease in women. (Vitamin C had no effect one way or the other in men.)
In one study, men who drank two or more cups of regular coffee daily (either instant, filtered, or espresso) had a 40% lower risk of developing the disease over ten years than did the men who did not drink coffee regularly. Those who drank more than four cups had the lowest risk. The benefits and risks of caffeine consumption vary depending on the individual's health, so high consumption of coffee to prevent gallstones is not recommended as a general preventive measure.

Preventing Gallstones during Weight Loss. Maintaining a normal weight and avoiding rapid weight loss are the keys to reducing the risk of gallstones. Taking ursodiol or ursodeoxycholic acid (Actigall) during weight loss may reduce the risk for people who are very overweight and need to lose weight quickly. These agents are ordinarily used to dissolve existing gallstones. It should be noted, however, that this medication is very expensive. Of note is a 2001 study which suggested that orlistat (Xenical), an agent approved for treating obesity, may protect against gallstone formation during weight loss. The drug appears to reduce bile acids and other components involved in gallstone production. [ See Non-Surgical Therapy for Gallstones under What Are the Treatments for Gallstones?, below.]

Exercise

Exercising regularly and vigorously may reduce the risk of gallstones and gall bladder disease, even in people who are overweight. Studies on both men and women are reporting a lower risk for gallstones with exercise. One study indicated that men who performed endurance-type exercise (such as jogging and running, racquet sports, and brisk walking) for thirty minutes five times per week reduced their risk for gallbladder disease by up to 34%. The benefit depended more on the intensity of activity than the type of exercise. A 1999 study on women reported that exercise reduced gallstone risk regardless of whether women lost weight or not. Some researchers guess that in addition to controlling weight, exercise helps normalize blood sugar levels and insulin levels, which, if abnormal, may contribute to gallstones.

Nonsteroidal Anti-Inflammatory Drugs

Some data had indicated that taking nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin or ibuprofen, protects against the development of gallstones. A recent study of more than 400 chronic arthritis sufferers who took NSAIDs regularly, however, reported no significant protection.

HOW ARE GALLSTONES AND GALLBLADDER DISEASE DIAGNOSED?

The diagnostic challenge posed by gallstones is to be sure that abdominal pain is caused by stones and not by some other condition. Ultrasound or other imaging techniques usually detect gallstones readily. Nevertheless, because gallstones are common and most cause no symptoms, simply finding stones does not necessarily explain a patient's pain, which may be caused by numerous other conditions.

Ruling out Other Disorders

In patients with abdominal pain, causes other than gallstones are usually responsible if the pain lasts less than 15 minutes, frequently comes and goes, or is not severe enough to limit activities.

Irritable Bowel Syndrome. Irritable bowel syndrome (IBS) has some of the same symptoms as gallbladder disease, including difficulty digesting fatty foods. In IBS, however, pain usually occurs in the lower abdomen.

Other Conditions with Similar Symptoms. Acute appendicitis, inflammatory bowel disease (Crohn's disease or ulcerative colitis), pneumonia, stomach ulcers, hiatal hernia, hepatitis, kidney stones, urinary tract infections, diverticulosis or diverticulitis, pregnancy complications, and even a heart attack may mimic a gallbladder attack.

Physical examination

A physical exam often reveals tenderness in the upper right area of the abdomen in acute cholecystitis and sometimes in biliary colic. There is usually no tenderness in chronic cholecystitis.

Laboratory tests

Blood tests are usually normal in people with simple biliary colic or chronic cholecystitis. The following abnormalities may indicate gallstones or complications:

The enzyme alkaline phosphatase and bilirubin are usually elevated in acute cholecystitis, and especially choledocholithiasis (common bile duct stones). Bilirubin is the orange-yellow pigment found in bile. High levels cause jaundice, which gives the skin a yellowish tone.
Liver enzymes known as aspartate (AST) and alanine (ALT) aminotransferase are elevated when common bile duct stones are present. A three fold or more increase in ALT strongly suggests pancreatitis.
A high white blood cell count is a common finding in many (but not all) patients with cholecystitis.

Imaging Techniques for Diagnosing Gallstones and Infection (Cholecystitis)

Ultrasound. Ultrasound, the diagnostic method most frequently used to detect gallstones, is a simple, rapid, and noninvasive imaging technique.

The patient must not eat for six or more hours before the test, which takes only about 15 minutes.
Ultrasound detects gallstones as small as two millimeters in diameter with an accuracy of 90% to 95%.
During the same procedure, the physician can check the liver, bile ducts, and pancreas and quickly scan the gallbladder wall for thickening (characteristic of cholecystitis). Air in the gallbladder wall may indicate gangrene.

Ultrasound is not as useful for common bile duct stones and cannot image the cystic duct. According to one 2000 study, ultrasound is not useful for identifying cholecystitis in patients who do not have gallstones but have fever and abdominal pain. In this study, ultrasound detected some gallbladder abnormalities, no matter what the cause of the abdominal pain. In only a few cases were the symptoms actually caused by cholecystitis.

Cholescintigraphy. Cholescintigraphy, a nuclear imaging technique, is noninvasive and useful if ultrasound does not reveal cholecystitis but the condition is still suspected because of biliary pain. Cholescintigraphy can take one to two hours and even longer. The procedure involves the following steps:

A tiny amount of a radioactive dye is injected intravenously. This material is excreted into bile.
A camera detects the dye as it passes from the liver into the gallbladder.
If the dye does not enter the gallbladder, a gallstone may be obstructing the cystic duct, indicating acute cholecystitis. (The scan, however, cannot identify individual gallstones. Nor can it detect chronic cholecystitis.)

Occasionally, the scan gives false positive results, particularly in alcoholic patients with liver disease or patients who are fasting or receiving all nutrients intravenously.

Oral Cholecystography. Oral cholecystography uses a tablet containing a dye that is employed during an x-ray. It is useful for determining the structural and functional status of the gallbladder, often before nonsurgical procedures.

The patient eats a meal containing fat at noon the day before the test and a fat-free meal that evening. After the evening meal, the patient can not eat and can only drink water.
The patient takes a number of tablets at five minute intervals three hours after the last meal the night before the procedure.
The dye is absorbed by the intestine, excreted by the liver, and concentrated in the gallbladder.
The following day, the patient is x-rayed.
Gallstones are outlined on the x-ray by the dye.

Diagnosing Common Bile Duct Stones (Choledocholithiasis)

Detection of common bile duct stones is a complicated process. It requires blood tests, imaging tests, and invasive procedures that serve both for detection and removal. If there is evidence for common bile duct stones, such as dark urine, jaundice, pancreatitis, or elevated liver function tests, then other tests are required.

Laboratory Tests. The following are elevated on blood tests:

The enzyme alkaline phosphatase.
Bilirubin (orange-yellow pigment found in bile).
Liver enzymes known as aspartate (AST) and alanine (ALT) aminotransferase.

Imaging Tests.

Endoscopic Ultrasound (EUS). Standard ultrasound is useful for the diagnosis of gallstones, but it is not as sensitive for identifying common bile duct stones, particularly in obese patients or when intestinal gas is present. (Normal ultrasound results along with normal bilirubin and liver enzyme tests, however, are very accurate indications that no problems are present.) A variation called endoscopic ultrasound (EUS), however, may prove to be accurate for this purpose and even eventually serve as an alternative to ERCP. One 2000 study suggested that this technique may also be useful for detecting stones in pancreatitis when the cause is unknown.
Magnetic Resonance Cholangiography. Magnetic resonance imaging (MRI) techniques, particularly one called magnetic resonance cholangiography (MRC), are proving to be very effective in detecting common bile duct stones. Experts hope that eventually MRC will replace endoscopic retrograde cholangiopancreatography (ERCP), an invasive technique. ERCP is now used for both diagnosing and removing common duct stones. Studies in 2001 suggest, however, that MRC would eliminate the need for ERCP in only a small number of patients. [ See below. ] MRC is extremely sensitive in detecting biliary tract cancer. This imaging procedure is very expensive, however, and may not detect very small stones or chronic infections in the pancreas or bile duct.
Helical Computed Tomography. A technique known as helical, or spiral, computed tomography (CT) scanning is showing promise. With this process, the patient lies on a table that moves while a donut-like, low-radiation x-ray tube rotates around the patient. It shortens the time that a standard CT scan takes and obtains clearer images.

Invasive Tests. Even when noninvasive tests suggest common duct stones, only about 20% to 30% of patients actually have them. For a definite diagnosis, invasive procedures that serve for both detection and stone removal are required. The standard test in such cases is endoscopic retrograde cholangiopancreatography (ERCP). [For a description of ERCP see How Are Common Bile Duct Stones (Choledocholithiasis) Managed?]

One 2001 study suggested that findings in the following patients may suggest a higher risk for common duct stones and therefore the need for invasive tests:

Suggestive ultrasound tests in patients under 71 years old.
Elevated bilirubin levels in patients older than 70 years old.

Some physician recommend waiting 24 to 48 hours to see if the stones pass before performing these tests.

Diagnosing Gallstone-Related Pancreatis

It is sometimes difficult to differentiate between pancreatitis and acute cholecystitis, but a correct diagnosis is critical since treatment is very different. About 40% of pancreatitis cases are associated with gallstones. The risk for gallstone-associated pancreatitis is highest in older Caucasian and Hispanic women. About 25% of pancreatitis cases are severe, and this rate is much higher in people who are obese.

Blood Tests. Blood tests showing high levels of pancreatic enzymes (amylase and lipase) can usually indicate the diagnosis of pancreatitis. Elevated levels of alanine aminotransferase are very specific in identifying gallstone pancreatitis.

Imaging Tests. Imaging techniques are useful in confirming a diagnosis. Ultrasound is often used. A computed tomography (CT) scan, along with a number of laboratory tests, can determine the severity of the condition.

WHAT IS THE GENERAL APPROACH FOR TREATING GALLSTONES AND GALLBLADDER DISEASE?

Acute pain from gallstones and gallbladder disease is usually treated in the hospital, where diagnostic procedures are performed to rule out other conditions and complications. There are three approaches to gallstone treatment:

Expectant management.
Nonsurgical removal of the stones.
Surgical removal of the gallbladder.

Expectant Management

Guidelines from the American College of Physicians state that when a person has no symptoms, the risks of both surgical and nonsurgical treatment for gallstones outweigh the benefits. Experts suggest a wait-and-see approach for such patients, which they have termed expectant management. Exceptions to this policy are those at risk for complications from gallstones, including the following:

People at risk for gallbladder cancer (such as those with calcified gallbladders).
Pima Native Americans.
Patients with stones larger than three centimeters.
People who have large polyps on the gallbladder.

One study reported that very small gallstones increase the risk for acute pancreatitis, a serious condition. Some experts therefore believe that gallstones smaller than five millimeters warrant immediate surgery.

There are some minor risks with expectant management for asymptomatic or low-risk individuals. Gallstones almost never spontaneously disappear, except sometimes when they are formed under special circumstances, such as pregnancy or sudden weight loss. At some point, then, the stones may cause pain, complications, or both, and require treatment. Some studies suggest that the patient's age at diagnosis may be a factor in the possibility of future surgery. The probabilities are as follows:

30% for people diagnosed at 30 years old. (The slight risk of developing gallbladder cancer might encourage young adults who are asymptomatic to have their gallbladders removed.)
20% at 50 years old.
15% at 70 years old.

Treatment for Patients with Symptoms

Gallstones are the most common cause for hospital admissions of patients with severe abdominal pain. The approach to patients who come to the hospital with emergency symptoms suggesting gallstones (ie, steady and severe pain on the right) may be the following:

Administration of intravenous fluids and pain killers, usually meperidine (Demerol). (Some physicians believe morphine should be avoided for gallbladder disease.)
Drugs to stop vomiting.
Antibiotics for 12 to 24 hours. These may be given to patients with evidence of infection (acute cholecystitis), including fever or an elevated white blood cell count.

The patient is given diagnostic tests. Depending on results, the approach may be as follows.

Normal Test Results and no Severe Pain or Complications. If the patient has no fever or underlying serious medical problems and shows no signs of severe pain or complications, and if laboratory tests are normal, then the patients may be discharged with oral antibiotics and pain relievers.

Tests that Show Gallstones and Presence of Pain but no Infection. Patients with pain and tests that indicate gallstones, but who do not show signs of infection have the following options:

They may electively choose to have the gallbladder removed (called cholecystectomy) at their convenience. The most common procedure is now laparoscopy, a less invasive technique than open cholecystectomy.
A minority of such patients may be candidates for a stone-breaking technique called lithotripsy (The treatment works best on solitary stones that are less than two centimeters in diameter.)
Drug therapy for gallstones is available for some patients who are unwilling to undergo surgery or who have serious medical problems that increase the risks of surgery. Nonsurgical treatment, however, usually cannot be used for patients who have acute gallbladder inflammation or common bile duct stones since delaying or avoiding surgery could be very hazardous in these cases. Recurrence rates are high with non-surgical options. The introduction of laparoscopic cholecystectomy has greatly reduced the use of non-surgical therapies.

Tests Indicating Gallbladder Infection (Acute Cholecystitis). If tests indicate acute gallbladder infection, early gallbladder removal is often warranted. It is usually performed at least 48 hours after admission when inflammation has improved. Some patients can wait longer.

Tests Showing Gallstone-Associate Pancreatitis. Patients who have developed gallstone-associate pancreatitis almost always require surgery, either laparoscopic or open cholecystectomy.

Tests Suggesting Common Duct Stones. If noninvasive diagnostic tests suggest obstruction from common duct stones, the patient is given endoscopic retrograde cholangiopancreatography (ERCP) for confirming the diagnosis and for removing the stones. This technique is used urgently along with antibiotics if infection is present in the common duct (cholangitis).

WHAT ARE THE MEDICATIONS USED FOR GALLSTONES?

Oral Dissolution Therapy

Oral dissolution therapy uses bile acids in pill form to dissolve gallstones and may be used in conjunction with lithotripsy. [ See below.] Ursodiol or ursodeoxycholic acid (Actigall) and chenodiol (Chenix) are the standard oral bile acid drugs used for dissolution. Most physicians prefer ursodeoxycholic acid, which is considered to be among the safest of common drugs and does not seem to have significant side effects. Long-term treatment appears to notably reduce the risk of biliary pain and acute cholecystitis. The treatment is only moderately effective, however, since gallstones recur in the majority of patients.

Appropriate Candidates. Patients most likely to benefit from oral dissolution therapy are the following:

Patients with small stones (less than 1.5 cm in diameter) with high cholesterol content.

Patients that probably will not benefit from this treatment are the following:

Those that have gallstones that are calcified or composed of bile pigments.
Obese patients.

Only about 30% of patients, in fact, are candidates for oral dissolution therapy, and the number may be much lower, since compliance is often a problem. The treatment can take up to two years and can cost thousands of dollars per year.

Contact Dissolution Therapy

Contact dissolution therapy requires the injection of the organic solvent methyl tert-butyl ether (MTBE) into the gallbladder to dissolve gallstones. This is a somewhat technically difficult and hazardous procedure and should be performed only by experienced physicians in hospitals where research on this treatment is being done. Preliminary studies indicate that MTBE rapidly dissolves stones. The ether remains liquid at body temperature and dissolves gallstones within five to twelve hours. Serious side effects include severe burning pain.

HOW IS EXTRACORPOREAL SHOCK WAVE LITHOTRIPSY USED FOR GALLSTONES?

Gallstone fragmentation by extracorporeal shock wave lithotripsy (ESWL) may be an appropriate therapy for some patients who cannot undergo surgery. The treatment works best on solitary stones that are less than two centimeters in diameter. Less than 15% of patients are good candidates for lithotripsy. The typical procedure is as follows:

The patient typically sits in a tub of water.
High-energy, ultrasound shock waves are directed through the abdominal wall toward the stones.
The shock waves travel through the soft tissues of the body and break up the stones.
The stone fragments are then usually small enough to be passed through the bile duct and into the intestines.
Lithotripsy is generally combined with bile acid treatment to help dissolve the fragmented pieces of the original gallstone.

A 2000 study compared the ability of different shock wave lithotripsy machines to fragment gallstones. The HM3, Modulith SLX, and Lithostar C machines had the best record for breaking stones into the smallest fragments. The use of lasers for lithotripsy is under investigation.

Complications

Although the mortality rate for lithotripsy is essentially zero, complications include pain in the gallbladder area and pancreatitis, usually occurring within a month of treatment. In addition, not all of the fragments may clear the bile duct. Adding erythromycin to the treatment regimen may help remove these fragments. About 35% of patients who are left with fragments are at risk for further problems, some severe. The chance of recurrence is high with this procedure, and in one study, 45% of patients eventually required surgery.

WHAT ARE THE SURGICAL PROCEDURES FOR GALLSTONES AND GALLBLADDER DISEASE?

General Considerations for Gallbladder Removal (Cholecystectomy)

Every year, about 500,000 people have their gallbladders removed. The gallbladder is not an essential organ, and even today, only surgical removal of the gallbladder ( cholecystectomy) guarantees that the patient will not suffer a recurrence of gallstones. This is one of the most common surgical procedures performed on women and can even be performed on pregnant women with low risk to the baby and mother. The primary advantages of surgical removal of the gallbladder over nonsurgical treatment are both the elimination of gallstones and also the prevention of gallbladder cancer.

Appropriate Surgical Candidates. Candidates for surgery often have one of the following conditions:

One very severe gallstone attack.
Several less severe gallstone attacks.
Cholecystitis.
Pancreatitis.

Timing of Surgery. Cholecystectomy may be performed within several days of hospitalization for an acute attack. Some patients can be safely discharged after treatment of an attack of acute cholecystitis and undergo elective surgery several months later.

General Outlook. Although cholecystectomy is very safe, as with any operation, there are risks of complications depending on whether the procedure is elective or an emergency procedure.

When cholecystectomy is performed as elective surgery, the mortality rates are very low. (Even in the elderly, mortality rates are only between 0.7% to 2%).
Emergency cholecystectomy carries a much higher mortality rate (as high 19% in ill elderly patients).

Long-Term Effects of Gallbladder Removal. Although removal of the gallbladder has not been known to cause any long-term adverse effects aside from occasional diarrhea, some researchers have been concerned about its effects on the body's cholesterol levels. One study found that within three days of the operation, levels of total cholesterol and LDL returned to their preoperative levels. After three years, however, some types of cholesterol not ordinarily associated with coronary artery disease had risen significantly. These results did not necessarily indicate any increased risk for coronary artery disease, but they did show that the metabolism of cholesterol by the liver had been altered. People who have had their gallbladders removed should have their cholesterol levels checked periodically, as should every adult. Short-term treatment with cholesterol-lowering drugs containing HMG-CoA reductase inhibitors, commonly known as statins, such as pravastatin (Pravachol), appears to lower cholesterol levels in surgical patients.

Open Procedures versus Laparoscopy

Until the early 1990s, open cholecystectomy (the removal of the gallbladder through an abdominal incision) was the standard treatment. Now, laparoscopic cholecystectomy (commonly called lap choly ), which uses small incisions, is the most commonly used surgical approach. First performed in 1987, laparoscopy is now used in nearly 75% of all cholecystectomies in the United States. Because of the appeal of laparoscopy, gallstone operations have increased by as much 40% in some parts of the country. Of concern is a significant increase in its use by patients who have inflammation in the gallbladder but no gallstones and in those who have gallstones but no symptoms.

Advantages of Laparoscopy. Laparoscopy has some significant advantages over open cholecystectomy:

The patients can leave the hospital and resume normal activities earlier than with open surgery.
The incisions are small, and there is less post-operative pain and disability than with the open procedure.
Laparoscopy has fewer complications.
One study reported that although the treatment cost of laparoscopy was higher than the open procedure, the more rapid recovery with laparoscopy translated into fewer sick days and so a greater reduction in overall costs.

Advantages of Open Cholecystectomy. Some experts believe, however, that the open procedure has a number of advantages compared to laparoscopy:

It is faster to perform.
It poses less of a risk for bile duct injury, which occurs in only 0.1% to 0.2% of open procedures. (It has more overall complications than laparoscopy, however.)

Appropriate Candidates for Laparoscopy or Open Cholecystectomy
Laparoscopy	Open Cholecystectomy
Treatment of choice for most adult patients, with or without symptoms, who have chosen to have their gallbladders removed.	Patients who have had extensive previous abdominal surgery.
Overweight patients (as long as abdominal wall is not excessively thick).	Patients with complications of acute cholecystitis (empyema, gangrene, perforation of the gallbladder).
Patients with acute cholecystitis. (About 5% to 20% will need to convert to open surgery.)	Elderly patients. (Those over 80 are particularly likely to have lower complication rates from open cholecystectomy than laparoscopy.)
Patients with acalculous gallbladder disease (without stones).	Seriously ill patients with acute cholecystitis who do not respond to fluid aspiration (percutaneous cholecystostomy).
Possible candidates with very experienced surgeons): Patients with acute gallstone pancreatitis that has subsided. Patients with prior surgery in the upper abdomen. Pregnant women with symptomatic gallstone.

Laparoscopic Cholecystectomy

The Procedure. With laparoscopy, removal of the gallbladder is typically performed as follows:

Laparoscopic cholecystectomy requires general anesthesia, although it is now mostly done as outpatient surgery. (One study suggested that 24-hour monitoring afterward was not necessary and the patient could go home the same day.)
The surgeon inserts a needle through the navel and pumps carbon dioxide gas through it and into the abdomen to create space in the abdomen. (Of note, a 2000 study recommended using a gasless procedure for elderly patients. Such patients are more likely to require a longer operating time, and the on-going pressure from the carbon dioxide increases the risk for problems that require conversion to an open procedure.)
Small incisions, one or two 10 to 12 mm (around half an inch) and three 5 mm (.20 inches), are made in the abdomen .
The surgeon inserts a laparoscope (a thin telescope) which contains a small surgical instrument and a tiny camera that relays an image to a video monitor.
The surgeon separates the gallbladder from the liver and other areas and removes it through one of the incisions.

Risk Factors for Conversion from Laparoscopy to an Open Procedure. In about 5% to 10% of laparoscopies, conversion to open cholecystectomy is required during the procedure. Some reasons for conversion to open surgery include the following:

Possible or known injury to major blood vessels.
Internal structures not clearly visible.
Unexpected problems that cannot be corrected with laparoscopy.
Common bile duct stones that cannot be removed with laparoscopy or subsequent ERCP.

Complications and Side Effects of Surgery. Complications include the following:

There is a relatively high incidence of nausea and vomiting after laparoscopic cholecystectomy, which can be treated with injections of metoclopramide. Preoperative anti-nausea agents, such as granisetron, may prevent these effects.
Injury to the bile duct. (This can lead to liver damage and is the most serious complication of laparoscopy. It is more common with laparoscopy than with the open procedure.)
In about 6% of procedures, the surgeon misses gallstones or they are spilled and remain in the abdominal cavity. In a small percentage of these cases, the stones cause obstruction, abscesses, or fistulas (small channels) that require open surgery.
As with all surgeries, there is a risk for infection, but it is very low.

Patients should not be shy about inquiring into the number of laparoscopies the surgeon has performed. (It should not be fewer than 30.)

Open Cholecystectomy

Before laparoscopy, the standard surgical treatment for gallstones was open cholecystectomy (surgical removal of the gallbladder through an abdominal incision), which requires a wide incision and leaves a larger surgical scar. The patient usually needs to stay in the hospital for five to seven days and may not return to work for a month. Complications include bleeding, infections, and injury to the common bile duct. The risks of this procedure increase with other factors, such as the age of the patient or if the surgeon needs to explore the common bile duct for stones at the same time.

Needlescopic Cholecystectomy

Procedures that use even fewer and smaller incisions than laparoscopy are being developed. There are many variations including those referred to as twin-port, mini-site, or mini or micro-laparoscopic surgeries. These procedures make even fewer incisions (two to three) and smaller ones (1.2 to 3 mm or .04 to .12 in.). It should be noted, however, that these procedures still require one large incision (10 to 12 mm or about half an inch). They are still investigative and have some disadvantages:

They employ fiberoptics to view the surgical areas that are less bright than those used with conventional laparoscopy.
The instruments are very fragile.
The field of vision is very limited.

Their benefits are also not proven. Although such surgeries are proving to be feasible in cases unlikely to have complications, studies are mixed on whether they reduce postoperative pain or improve recovery time beyond that of standard laparoscopy.

Treatment for Patients with Very Severe Infection (Cholecystitis)

Percutaneous cholecystostomy. Percutaneous cholecystostomy is a procedure that may be used in seriously ill patients with severe gallbladder infection who cannot tolerate immediate surgery. This procedure uses a needle to withdraw (aspirate) fluid from the gallbladder. A drainage catheter is inserted through the skin and into the gallbladder for about six to eight weeks while the fluid drains out. After that time, if possible, laparoscopy or an open cholecystectomy may be performed.

Gallbladder Aspiration. With this procedure, fluid is aspirated in one procedure while the gallbladder is viewed using ultrasound. It does not require an indwelling catheter afterward and may have fewer complications than percutaneous cholecystostomy.

HOW ARE COMMON BILE DUCT STONES (CHOLEDOCHOLITHIASIS) MANAGED?

Common duct stones are suspected during cholecystectomy in 10% to 15% of patients. Historically, the approach to managing common duct stones (choledocholithiasis) has been the following:

In the past, when common bile duct stones were suspected, the approach was open surgery (open cholecystectomy) and surgical exploration of the common bile duct.
Now endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic sphincterotomy (ES) are the most frequently used procedures for detecting and managing common duct stones. The procedure involves the use of an endoscope (a flexible telescope containing a miniature camera and other instruments), which is passed through the mouth and down to the bile duct entrance. [ See Below. ]
Laparoscopic cholecystectomy is increasingly being used for detection and removal of common duct stones. In such cases, it is used in combination with ultrasound or a cholangiogram (an imaging technique that uses a dye injected into the bile duct and x-rays to view any stones.) How and when to use this technique for common duct stones, however, is currently under debate. [ See Below. ]

Endoscopic Retrograde Cholangiopancreatography (ERCP) with Endoscopic Sphincterotomy (ES)

The ERCP and ES Procedure. A typical ERCP and endoscopy sphincterotomy (ES) procedure includes the following steps:

The patient is given a sedative and is told lie on his or her left side.
An endoscope (a tube containing fiberoptics connected to a camera) is passed through the mouth and stomach and into the duodenum (top part of the small intestine) until it reaches the point where the common bile duct enters. This does not interfere with breathing, but the patient may have a bloating sensation.
A thin catherter is then passed through the endoscope.
Contrast material (a dye) is injected through the catherter into the opening of the duct. The dye allows visualization using an x-ray of the biliary tree (the system of ducts through which bile flows, including the common bile duct) and any stones contained in the area.
Instruments may also be passed through the endoscope to remove any stones that are detected.
A tiny incision is usually made in the orifice of the common bile duct and through the muscles that enclose the lower common bile duct (called the sphincter of Oddi). This serves to widen the junction between the common bile duct and intestine (called the ampulla of Vater ) so that the stones can be extracted more easily. This part of the procedure is the endoscopic sphincterotomy (ES). (It is also sometimes referred to as papillotomy, although this is a slightly different variation.)
One recent alternative to ES is the use of a small inflatable balloon (called endoscopic balloon dilation) that opens up the ampulla of Vater to allow stones to pass and so avoid cutting the muscles.
Once the junction has been opened, the stones may pass out on their own or they may be extracted with the use of tiny baskets or balloons.
This procedure is usually followed by later cholecystectomy (removal of the gallbladder) to eliminate the source of the stones. [See What Are the Surgical Procedures for Gallstones and Gallbladder Disease?.]

When ERCP with ES is Used.

When stones are detected prior to gallbladder removal (open or laparoscopic cholecystectomies).
When stones are found in the common duct after cholecystectomy.
Urgent ERCP plus antibiotics for patients with gallstone cholangitis (serious infection in the common bile duct).
For acute pancreatitis caused by gallstones. (Urgent ERCP for this condition, compared to conservative treatment, has been controversial. One study reported that only patients who had infection and persistent obstruction in the ducts benefited from urgent intervention. A 2000 analysis of four other studies, however, reported that ERCP with ES significantly improved survival rates and reduced complications.)

Complications. Complications of ERCP and endoscopy sphincterotomy occur in up to 10% of cases and can be serious, with mortality rates of about 0.5%. They range from mild to severe and include the following:

Pancreatitis (inflammation of the pancreas). (This condition occurs in 5% of cases and can become life threatening. Younger adults are at higher risk than the elderly. The use of the drug gabexate may lower the risk.)
Post-Operative Infection. (Antibiotics may be given before the procedure to prevent infection, although one study reported that they had little benefit.)
Bleeding. (Occurs in 2% of cases. Increased risk in patients taking anti-clotting drugs and those who have cholangitis. This is treated by flushing with epinephrine.)
Perforations (rare).
Long-term complications include stone recurrence and abscesses.

ERCP and endoscopic sphincterotomy are difficult procedures and patients must be certain their physician is experienced with them, ideally having performed at least 180 ERCPs. Under such circumstances, ERCP can usually be performed successfully even in critically ill patients on mechanical ventilators.

Laparoscopy Cholecystectomy and Cholangiography for Detection and Removal of Common Duct Stones

Surgeons are now increasingly using laparoscopic cholecystectomy plus an imaging technique called cholangiography instead of ERCP when common duct stones are suspected. The laparoscopic procedure for common duct stones is generally as follows.

Incisions are made as they would be in laparoscopic cholecystectomy. [ See the description under What Are the Surgical Procedures for Gallstones and Gallbladder Disease? .]
A tiny opening is made in the cystic duct which connects the gallbladder to the bile duct, and a thin tube is introduced to perform a cholangiogram. (In this procedure, a dye is administered to reveal the stone's location on x-rays.)
If stones are identified, the surgeon inserts a tube with an inflatable balloon that is used to widen the duct.
Stones are usually retrieved or withdrawn from the duct either with the use of a balloon or with a tiny basket.
If laparoscopy is unsuccessful, then ERCP or open surgery is performed.

Experts are debating the choice of laparoscopy and cholangiography as an alternative to preoperative ERCP for detecting and managing common duct stones. Many surgeons believe that laparoscopy is becoming safe and effective and should be the first choice. They recommend ERCP only for high-risk cases (eg, gallstone-caused pancreatitis, infection in the duct, and patients who cannot take general anesthesia). Still, laparoscopy for common duct stones should be performed only by surgeons experienced in this new and demanding technique.

Choledocholithotomy

Choledocholithotomy, or common bile duct exploration, is used to remove large stones or in cases when the duct anatomy is complex. In this procedure, the physician carries out open abdominal surgery and extracts gallstones through an incision in the common bile duct. Routinely, a so-called T-tube is temporarily left in the common bile duct after surgery and the physician x-rays the bile duct through the tube seven to ten days postoperatively to determine if any stones remain in the duct.

Lithotripsy for Common Bile Duct Stones

Shock wave lithotripsy is an option in certain cases for bile duct stones that cannot be extracted.

Mechanical Endoscopic Lithotripsy. Endoscopy with mechanical lithotripsy employs a tiny steel crushing basket, which is inserted through the endoscope and into the common bile duct. The basket opens to trap and then crush the stone. It is capable of crushing and removing very large stones. The overall success rate is 80% to 90%, although 20% to 30% of patients require more than one treatment.

Extracorporeal Shock Wave Lithotripsy. Extracorporeal shock wave lithotripsy is an option in certain cases for bile duct stones as it is for stones in gallbladder. [ See a discussion of ESWL under What Is the General Approach for Treating Gallstones and Gallbladder Disease? , above. ]

WHERE ELSE CAN HELP FOR GALLSTONES AND GALLBLADDER DISEASE BE OBTAINED?

National Digestive Diseases Information Clearinghouse, NIDDK, NIH, 31 Center Drive, MSC 2560, Bethesda, MD 20892-2560, USA Call (301-654-3810) or on the Internet (http://www.niddk.nih.gov)

American Gastroenterological Association, American Digestive Health Foundation, 7910 Woodmont Avenue, 7th Floor, Bethesda, MD 20814. Call (301 654-2055) or (http://www.gastro.org)

American Society for Gastrointestinal Endoscopy, 13 Elm Street, Manchester, MA 01944-1314. Call (978-526-08330) or (http://www.asge.org/)

American College of Gastroenterology, 4900 B South 31 St., Arlington, VA 22206. Call (703-820-7400), or (http://www.acg.gi.org/)

American Liver Foundation, 75 Maiden Lane, Suite 603, New York, NY 10038. Call (800-GO LIVER) or (800-465-4837) or on the Internet (http://www.liverfoundation.org/)

National voluntary organization dedicated to preventing, treating, and curing gallbladder diseases through research and education. Provides patient brochures, video and audio tapes.