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•	Introduction
•	Symptoms
•	Prognosis
•	Risk Factors
•	Prevention
•	Diagnosis
•	Treatment
•	Surgery
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Gallstones and Gallbladder Disease

Highlights

Risk Factors

• Hormone replacement therapy (HRT). Women who use HRT have a higher risk for gallstones or gallbladder surgery. All types of HRT increase the risk, but a 2005 Journal of the American Association study reported that the risks are greater for estrogen alone therapy than combined estrogen and progesterone therapy.
• Metabolic syndrome. Metabolic syndrome may be a risk factor for gallstones as well as heart disease. Metabolic syndrome is a cluster of conditions that include high cholesterol, high blood pressure, high blood sugar, and obesity. Obesity itself is also a risk factor for gallstone disease.

Diet

• Fats. Consuming trans-fatty acids may lead to gallstone formation in men, according to a 2005 study published in the Archives of Internal Medicine. Trans-fatty acids are partially hydrogenated vegetable oils found in stick margarine, fried foods, and processed baked foods. By contrast, mono-unsaturated fats (found in olive and canola oils) and omega-3 fatty acids (found in fish oil) appear to decrease gallstone risk.
• Carbohydrates. High intakes of carbohydrates and sugar can increase gallstone risk, suggests a 2005 study in Gut. The researchers recommend that people at risk for gallstones avoid low fat, high carbohydrate diets.
• Nuts. Several recent studies suggest that eating more nuts may reduce the risk of developing gallstones.

Surgery

Laparoscopic gallbladder surgery is safe for obese people. Laparoscopic cholecystectomy is usually recommended over open cholecystectomy for gallbladder removal. However, some surgeons are concerned that very obese people may not be good candidates for this procedure. A 2005 study indicated that the surgery may take longer to perform in obese people, but it is safe and works well.

Introduction

Gallstones are small, hard pellets that can form in the gallbladder, a sac-like organ that lies under the liver on the right side of the abdomen. Most people with gallstones don't even know they have them. But in some cases a stone may cause the gallbladder to become inflamed, resulting in pain, infection, or other serious complications.

Bile and the Gallbladder

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

• Bile is important for the digestion of fat. It 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 bile duct. (This system of ducts through which bile flows is called the biliary tree).

Click the icon to see an image of the biliary tree.

• The gallbladder is a 4-inch sac with a muscular wall that is located under the liver. Here, most of the bile fluid (about 2 to 5 cups a day) is removed, leaving a few tablespoons of concentrated bile.
• The gallbladder serves as a reservoir until bile is needed in the small intestine to digest fats. This need is triggered by a hormone called cholecystokinin, which 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 part of the digestive process enables the emulsified fat along with important fat-absorbable nutrients (e.g., vitamins A, D, E, and K) to pass through the intestinal lining and enter the blood stream.

Formation of Gallstones (Cholelithiasis)

Gallstones can range from a few millimeters to several centimeters in diameter. Most are formed from cholesterol. The other most common gallstone is known as a pigment stone. Patients can also have mixture of these two. Another 15% are known as pigment stones, are formed from a brown-colored substance called calcium bilirubinate.

Cholesterol Stones. Although cholesterol makes up only five percent of bile, about three-quarters of the gallstones found in the US population are formed from this substance. Cholesterol gallstones typically form in the following way:

• Cholesterol is not very soluble, so in order to remain suspended in fluid it must be transported within clusters of bile salts called micelles. If there is an imbalance between these bile salts and cholesterol, then the bile fluid turns to sludge. This thickened fluid consists of a mucus gel containing cholesterol and calcium bilirubinate.
• If the imbalance worsens, cholesterol crystals form (called supersaturation), which can eventually form gallstones.
• This process of gallstone formation is referred to as cholelithiasis. It is very slow and most often painless.

Click the icon to see an image of gallstones.

Supersaturation and cholelithiasis can occur as a result of various abnormalities, although the cause is not entirely clear. There are many events that may promote cholelithiasis.

• The liver secretes too much cholesterol into the bile.
• The gallbladder may not be able to empty normally, so that the bile becomes stagnant.
• The cells lining the gallbladder may not be able to absorb cholesterol and fat from bile efficiently.
• High levels of bilirubin have been observed in patients with gallstones. Bilirubin is a substance normally formed by the breakdown of hemoglobin in the blood and it is excreted in bile. Some experts believe it may play an important role in cholesterol gallstones.

Pigment Stones. Pigment stones are composed of calcium bilirubinate, or calcified bilirubin. Pigment stones can be black or brown.

• Black stones form in the gallbladder and are the more common type. In fact, they represent 20% of all gallstones in the US. They are more likely to develop in people with hemolytic anemia (a relatively rare anemia where red blood cells are destroyed) or cirrhosis (a scarred liver).
• Brown pigment stones are more common in Asian populations. They contain more cholesterol and calcium than black pigment stones and are more likely to occur in the bile ducts. Infection plays a role in the development of these stones. One report suggested that bacteria or other microorganisms may trigger oxidation--a damaging chemical process in the body--which, in this case, can cause changes that lead to pigment stone formation.

Choledocholithiasis

Gallstones can also be present in the common bile duct. This is called choledocholithiasis.

Click the icon to see an image of gallstone obstruction.

Secondary Common Bile Duct Stones. In most cases, common bile duct stones originally form in the gallbladder and pass into the common duct (called secondary stones). Choledocholithiasis occurs in about 10% of patients who have gallstones.

Primary Common Bile Duct Stones. In less common cases, the stones form in the common duct itself (called primary stones). Primary common duct stones are usually of the brown pigment type and are more likely to cause infection than secondary common duct stones.

Gallbladder Diseases Without Stones

Gallbladder disease can occur without stones. This is called acalculous gallbladder disease.

Gallbladder disease can occur without stones, a condition called acalculous gallbladder disease. It can be acute (arising suddenly, often as a one-time occurrence) or chronic (persistent).

• 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 impaired ability to contract and empty its bile (i.e. impaired motility).
• Chronic acalculous gallbladder disease (also called biliary dyskinesia) appears to be caused by muscle defects or other problems in the gallbladder that cause impaired motility.

Diagnosing Acalculous Gallbladder Disease

Diagnosing Acute Acalculous Gallbladder Disease. Symptoms are similar to acute cholecystitis with gallstones, but they may be obscured by other medical conditions, since patients with this condition are often critically ill with other illnesses.

Diagnosing Chronic Acalculous Gallbladder Disease. Chronic acalculous gallbladder disease is usually diagnosed when a patient complains of gallbladder symptoms but there is no evidence of stones using standard imaging techniques. (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 Acalculous Gallbladder Disease

Treatment for Acute Acalculous Gallbladder Disease. Acute acalculous gallbladder disease has a very high rate of serious complications (gangrene, perforation, and pus in the gallbladder, so emergency removal of the gallbladder is warranted.

Treatment for Chronic Acalculous Gallbladder Disease. Most patients (75 - 90%) diagnosed with chronic acalculous gallbladder disease are relieved of their symptoms by cholecystectomy (removal of the gallbladder). Between 10 - 23%, however, still experience pain. Surgery is most warranted in these patients when the symptoms are caused by impaired emptying of the gallbladder.

Symptoms

About 90% of gallstones provoke no symptoms at all. If they 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 10 years is not known, although some doctors 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:

• The primary symptom is typically a steady gripping or gnawing pain in the upper right abdomen near the rib cage, which can be quite severe and can radiate to the upper back. Some patients with biliary colic experience the pain behind the breast bone.
• Nausea or vomiting may occur.
• Changes in position, over-the-counter pain relievers, and passage of gas do not relieve the symptoms.
• Biliary colic typically disappears after one to several hours. If it persists beyond this point then acute cholecystitis or more serious conditions may be present.
• The episodes typically occur at the same time of day but less frequently than once a week. Large or fatty meals can precipitate the pain, but it usually occurs several hours after eating and often wakes the patient during the night.
• 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.

Digestive complaints such as belching, feeling unduly full after meals, bloating, heartburn (burning feeling behind the breast bone), or regurgitation (acid back-up in the food pipe) are not likely to be caused by gallbladder disease. Conditions that may cause these symptoms include peptic ulcer, gastroesophageal reflux disease, or indigestion of unknown cause. [For more information, see In-DepthReports #19 Peptic Ulcers or #85 Gastroesophageal Reflux Disease.]

Symptoms of Gallbladder Inflammation (Acute Cholecystitis)

Between 1% and 3% of people with symptomatic gallstones develop inflammation in the gallbladder (acute cholecystitis), which occurs when stones or sludge obstruct the duct. The symptoms are similar to those of biliary colic but are more persistent and severe. They include the following:

• Pain in the upper right abdomen is severe and constant and can last for days. Pain frequently increases when drawing a breath.
• Pain also may radiate to the back or occur under the shoulder blades, behind the breast bone, or on the left side.
• About a third of patients have fever and chills.
• Nausea and vomiting may occur.

Anyone who experiences such symptoms should seek medical attention. Infection develops in about 20% of these cases, which increases the danger. Acute cholecystitis can progress to gangrene or perforation of the gallbladder if left untreated. (People with diabetes are at particular risk for serious complications.)

Symptoms of Chronic Cholecystitis or Dysfunctional Gallbladders

Chronic gallbladder disease (chronic cholecystitis) is marked by 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.
• Chronic diarrhea (four to 10 bowel movements every day for at least three months) may be a common symptom of gallbladder dysfunction.

Symptoms of Stones in the Common Bile Duct (Choledocholithiasis)

Stones lodged in the common bile duct (choledocholithiasis) can cause symptoms that are similar to those that lodge in the gallstone, although they may have the following:

• Jaundice (yellowish skin).
• Dark urine, lighter stools, or both.
• Heartbeat may become rapid and blood pressure may drop abruptly.
• Fever, chills, nausea and vomiting, and severe pain in the upper right abdomen. These symptoms suggest an infection in the bile duct (called cholangitis).

As in acute cholecystitis, patients who have these symptoms should seek medical help immediately. They may require emergency treatment.

Prognosis

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.

Gallstones, however, can cause obstruction at any point along the ducts that carry bile and, in such cases, symptoms can develop:

• 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 (acutecholecystitis), or both.
• About 10% of patients with symptomatic gallstones also have stones that pass into and obstruct the common bile duct (called choledocholithiasis).

Complications of Acute Cholecystitis

The most serious complication of acute cholecystitis is infection, which develops in about 20% of cases. It is extremely dangerous and life threatening if it spreads to other parts of the body (septicemia). 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 to gangrene. Studies have reported this complication in between 2 - 30% of cases. The highest risk is in men over 50 with a history of heart disease who have high levels of infection.
• Perforated Gallbladder. An estimated 10% of people with acute cholecystitis have a perforated gallbladder, which is a life-threatening condition. In general, this occurs in people who wait too long to seek help or who do not respond to treatment. This condition is most common in people with diabetes. The risk for perforation increases with a condition called emphysematous cholecystitis, in which gas forms in the gallbladder. Once the gallbladder has been perforated, people may experience a temporary decrease in pain. This is a dangerous event, however, since peritonitis (wide spread abdominal infection) develops afterward.
• Empyema. Pus in the gallbladder (called empyema) occurs in 2 - 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.
• Fistula. In some cases, the inflamed gallbladder adheres to and perforates nearby organs, such as the small intestine. In such cases a fistula (a channel) between the organs develops. Sometimes, in these cases, gallstones can actually pass into the small intestine, which can be very serious without immediate surgery.

Prompt surgery can nearly always prevent these complications.

Complications from Choledocholithiasis

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
• Being 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

Gallstones are present in about 80% of people with gallbladder cancer. Symptoms of gallbladder cancer are usually not present until the disease has reached an advanced stage and may include weight loss, anemia, recurrent vomiting, and a lump in the abdomen. When the cancer is caught at an early stage and has not spread deeper than the mucosa (the inner lining), removal of the gallbladder results in five-year survival rates of 68%. If cancer has spread to deeper layers, more extensive surgery or other treatments may be required.

This cancer is very rare, however, even among people with gallstones. Certain conditions in the gallbladder, however, pose a higher than average risk for cancer.

Gallbladder Polyps and Primary Scerlosing Cholangitis. Polyps (growths) are sometimes detected during diagnostic tests for gallbladder disease. Small gallbladder polyps (up to 10 mm) pose little or no risk, but large ones (greater than 15 mm) pose some risk for cancer, so the gallbladder should be removed. Patients with polyps 10 to 15 mm have a lower risk but they should still discuss removal of their gallbladder with their doctor.

Primary Sclerosing Cholangitis. Primary sclerosing cholangitis is a rare disease that causes inflammation and scarring in the bile duct. It is associated with a lifetime risk of 7% to 12% for gallbladder cancer. The cause is unknown although it tends to strike younger men with ulcerative colitis. Polyps are often detected in this condition and have a very high likelihood of malignancy.

Anomalous Junction of the Pancreatic and Biliary Ducts. With this rare inborn condition, the junction of the common bile duct and main pancreatic duct is outside the wall of the small intestine and forms a long channel between them. This problem poses a very high risk for cancers in the biliary tract.

Porcelain Gallbladders. Gallbladders are referred to as porcelain when their walls have become so calcified that they look like porcelain on an x-ray. Porcelain gallbladders have been associated with a very high risk for cancer, although recent evidence suggests that the risk is lower than previously thought. The incidence appears to depend on the presence of specific factors, such as partial calcification involving the mucosal lining. This condition may develop from a chronic inflammatory reaction that may actually be responsible for the cancer risk. Studies are reporting no higher risk with "true" porcelain gallbladders, in which the gallbladder walls are entirely calcified.

Risk Factors

About 20 million Americans harbor gallstones. Only 1% to 3% of the population, however, complains of symptoms during the course of a year, and less than have of these people will experience recurrent symptoms.

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, and pregnant women with stones are more likely to have symptoms than nonpregnant women. Surgery should be delayed until after delivery in most cases. In fact, gallstones may disappear after delivery. If surgery is needed laparoscopy is the safer approach.

Hormone Replacement Therapy. Several large studies have shown that use of hormone replacement therapy (HRT) doubles or triples the risk for gallstones or gallbladder surgery. A 2005 Journal of the American Medical Association study found that while all types of HRT raise the risks, estrogen alone has higher risks than combined estrogen and progesterone therapy. Estrogen has an effect on the liver and raises triglycerides, a fatty acid that increases the risk for cholesterol stones. Recent studies on HRT reporting negative effects on the heart and increased risks for breast cancer are also making this treatment a less attractive option for most postmenopausal women.

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 gallstones occur in this age group they are more likely to be pigment 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 system.
• Intravenous nutrition.

Ethnicity

Because gallstones are related to diet, particularly fat intake, the incidence of gallstones varies widely among nations and regions. For example, 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 brown pigment type.)

Native North and South Americans, such as Pima Indians in the US and native populations in Chile and Peru, are especially prone to developing gallstones. Pima women have an 80% chance of developing gallstones during their lives and virtually all Native American females in Chile and Peru develop gallstones during their lifetimes. Such cases are most likely due to a combination of genetic and dietary factors.

Genetics

Having a family member or close relative with gallstones may increase the risk of gallstones. Up to a third of cases of painful gallstones may be related to genetic factors, although the genetics of gallbladder disease remains poorly understood. Many genes may be involved, including those that lead to obesity or other risk factors that predispose 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 is 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 is highest in the following dieters:

• Those who lose 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.

Metabolic Syndrome

Metabolic syndrome is a cluster of conditions that includes obesity (especially belly fat), low HDL (good) cholesterol, high triglycerides, high blood pressure, and high blood sugar. Research suggests that metabolic syndrome is a risk factor for gallstones.

Low HDL Cholesterol and High Triglycerides and Their Treatment

Although gallstones are formed from supersaturation of cholesterol in the bile, high total cholesterol levels themselves are not necessarily associated with gallstones. Gallstone formation, however, is associated with low HDL cholesterol (the so-called good cholesterol) levels and high triglyceride levels. Some evidence suggests that high triglyceride levels may impair emptying actions of the gallbladder.

Unfortunately some fibrates, drugs used to correct these conditions, actually increase the risk for gallstones by increasing the amount of cholesterol secreted into the bile. They include gemfibrozil (Lopid), fenofibrate (Tricor), and bezafibrate (Bezalip). (Other cholesterol-lowering agents do not have this effect at all.) [See In-Depth Report #23: Cholesterol.]

Other Risk Factors

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

Crohn's Disease. Crohn's disease, an inflammatory bowel disorder, leads to poor reabsorption of bile salts from the digestive tract and substantially increases the risk of gallbladder disease. Patients over 60 and those who have had numerous bowel surgeries (particularly in the region where the small and large bowel meet) are at especially high risk.

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

Organ Transplantation. Bone marrow or solid organ transplantation increases the risk.

Medications. Octreotide (Sandostatin) poses a risk for gallstones. In addition the cholesterol-lowering drugs known as fibrates and thiazide diuretics may slightly increase the risk for gallstones.

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

Prevention

Diet plays a role in gallstones. The following discussions are some observations on specific dietary factors.

Role of Fats. Although fats have been associated with gallstone attacks--particularly saturated fats (found in meats, butter, and other animal products), evidence suggests that fat intake may have benefits under specific conditions.

Some studies, for example, have found a lower risk for gallstones in people who consume foods containing monounsaturated fats (found in olive and canola oils) or omega-3 fatty acids (found in canola, flaxseed, and, particularly, fish oil). Fish oil may be of particular benefit in patients who have high triglyceride levels by improving the emptying actions of the gallbladder.

Fiber. High intake of fiber has been associated with a lower risk for gallstones.

Nuts. Studies suggest that people may be able to reduce their risk of gallstones by eating more nuts (peanuts, walnuts, almonds).

Vegetable Protein. A 2004 epidemologic study found evidence that consumption of vegetable protein (such as soybean products) can help to prevent symptomatic gallstones.

Lecithin. Lecithin is a key component of bile. It contains choline and inositol--two compounds that are important for the breakdown of fat and cholesterol. Low levels of lecithin may precipitate the formation of cholesterol gallstones. Animal studies have suggested that lecithin-rich soy and buckwheat protein may protect against gallstones. (Buckwheat may be more protective than soy.) Dietary lecithin is available in health food stores and is found in eggs, soybeans, liver, wheat germ, and peanuts. There is no evidence, however, that lecithin supplements or foods containing it can prevent gallstones in humans.

Sugar. High-intake of sugar has been associated with an increased risk for gallstones. Diets that are high in carbohydrates (pasta, bread) can also increase risk. Carbohydrates are converted to sugar in the body.

Alcohol. A few studies, including one in 2003, reported a lower risk for gallstones with alcohol consumption. Even small amounts (one ounce per day) have been found to reduce the risk of gallstones in women by 20%. Moderate intake (defined as one or two drinks a day) also appears to have heart protective benefits. It should be noted, however, that even moderate intake increases the risk for breast cancer in women. Pregnant women, people who can't drink moderately, and people with liver disease should not drink at all.

Vitamin C. 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 women with high blood levels of ascorbic acid had a lower risk for gallbladder disease than women with low levels.

Coffee. 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 gallbladder disease over ten years than men who did not drink coffee regularly. Those who drank more than four cups had the lowest risk. A more recent study in 2000 did not find any general protective effect, although women with gallstones who drank coffee reported fewer symptoms than those who didn't.

Preventing Gallstones During Weight Loss

Maintaining a normal weight and avoiding rapid weight loss are the keys to reducing the risk of gallstones. Taking the medication ursodiol (also called ursodeoxycholic acid, or Actigall) during weight loss may reduce the risk for people who are very overweight and need to lose weight quickly. This medication is ordinarily used to dissolve existing gallstones. It should be noted, however, that it is very expensive. A promising 2001 study suggested that orlistat (Xenical), a drug 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.

Exercise

Exercising regularly and vigorously may reduce the risk of gallstones and gallbladder disease, even in people who are overweight. Studies are reporting a lower risk for gallstones in both men and women who exercise. Active sports exercise appears to be most protective for both men and women. A 1999 study of women reported that exercise reduced gallstone risk regardless of whether women lost weight or not. Some evidence suggests that that, in addition to controlling weight, exercise helps reduce cholesterol levels in the biliary tract, which could help prevent 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. Recent studies have been mixed, although a 2001 study reported significant protection against gallstone recurrence in people who took NSAIDs after being treated with lithotripsy.

NOTE: Long-term use of NSAIDS can cause stomach problems, such as ulcers and bleeding, and possible heart problems. In April 2005, the FDA asked drug manufacturers of NSAIDs to include a warning label on their product that alerts users of an increased risk for cardiovascular events and gastrointestinal bleeding. Talk to your doctor before taking these drugs.

The Effects of Cholesterol-Lowering Drugs

Although it would be reasonable to believe that agents used to lower cholesterol would protect against gallstones, they either have little effect or, in the case of fibrates, actually increase the risk. One study reported a weak association between statins and a lower risk for gallstones. These are the most effective drugs for treating high cholesterol and include lovastatin (Mevacor), pravastatin (Pravachol), simvastatin (Zocor), fluvastatin (Lescol), atorvastatin (Lipitor), and rosuvastatin (Crestor). Most evidence, however, has found no protection even from these agents. Reducing cholesterol itself, then, does not have any effect on cholesterol gallstones.

Diagnosis

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 ailments.

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.

Pancreatitis. 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 showing high levels of pancreatic enzymes (amylase and lipase) usually indicate a diagnosis of pancreatitis. Elevated levels of the liver enzyme alanine aminotransferase (ALT) are very specific in identifying gallstone pancreatitis.

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.

Pancreatic Cancer. Symptoms of pancreatic cancer may be very similar to those of gallbladder disease. It should be suspected if such symptoms are accompanied by weight loss or suspicious results from imaging tests of the pancreas.

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

Physical Examination

In patients with known gallstones, the doctor can often diagnose acute cholecystitis (gallbladder inflammation) the patient based on classic symptoms (e.g., constant and severe pain in the upper right quadrant of the abdomen). Imaging techniques, however, are necessary to confirm such a diagnosis. 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 aminotransferase (AST) and alanine aminotransferase (ALT) are elevated when common bile duct stones are present. A threefold 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.

Diagnosing Choledocholithiasis

General Guidelines. Common duct stones (choledocholithiasis) may be detected at one of several points:

• When the patient complains of gallbladder symptoms.
• At the same time that gallstones are diagnosed. (Common duct stones often accompany gallstones.)
• During or after performing surgery to remove the gallbladder for gallstones (cholecystectomy).

If the doctor only suspects common duct stones, however, identifying them is problematic. It requires blood tests, imaging tests, invasive procedures, or some combination that serve both for detection and possibly removal.

Laboratory Tests. Evidence that may suggest common bile duct stones includes dark urine, jaundice, or pancreatitis. In such cases, the doctor may perform certain blood tests. Elevated levels of the following suggest the presence of common duct stones:

• Alkaline phosphatase (ALP). Elevated levels of this enzyme are typically the first signs of common bile duct stones.
• Bilirubin (the orange-yellow pigment found in bile). Bilirubin levels increase after alkaline phosphatase rises.
• Liver enzymes known as aspartate aminotransferase (AST) and alanine aminotransferase (ALT). These enzymes may temporarily spike if the stone passes into the small intestine.

A number of techniques, particularly endoscopic retrograde cholangiopancreatography (ERCP), endoscopic ultrasound (EUS) and magnetic resonance cholangiography (MRC), are proving to be equally effective for detecting common bile duct stones. Only ERCP, however, allows removal of the stones, but it is invasive. A National Institutes of Health expert panel has endorsed the use of ERCP as a diagnostic technique for patients who are clearly ill with symptoms of gallstones. For patients who are not as sick, the panel recommended noninvasive imaging techniques.

Imaging Techniques

Ultrasound. Ultrasound is a simple, rapid, and noninvasive imaging technique. It is the diagnostic method most frequently used to detect gallstones and is the method of choice for detecting acute cholecystitis. The patient must not eat for six or more hours before the test, which takes only about 15 minutes. During the procedure, the doctor can check the liver, bile ducts, and pancreas and quickly scan the gallbladder wall for thickening (characteristic of cholecystitis).

Ultrasound detects gallstones as small as two millimeters in diameter with an accuracy of 90% to 95%. Some experts recommend that if an ultrasound does not detect stones, but gallstones are still strongly suspected, the test should be repeated.

Air in the gallbladder wall may indicate gangrene.

Ultrasound does not appear to be very useful for identifying cholecystitis in symptomatic patients who do not have gallstones. In one study, ultrasound detected some gallbladder abnormalities, no matter what the cause of the abdominal pain. In only a few cases, however, were the symptoms actually caused by cholecystitis.

Ultrasound is also not as useful for common bile duct stones and cannot image the cystic duct. (Nevertheless, normal ultrasound results along with normal bilirubin and liver enzyme tests are very accurate indications that there are no stones in the common bile duct.)

An ultrasound variation called endoscopic ultrasound (EUS) is accurate and useful for patients with an intermediate risk for common bile ducts stones. Its accuracy is comparable to endoscopic retrograde cholangiopancreatography (ERCP), the standard for diagnosing stones in the common bile duct. However, if common duct stones are detected they cannot be removed. It is useful then when common bile duct stones are suspected but the patient is not clearly ill.

X-Rays. Standard x-rays of the abdomen may detect calcified gallstones and gas. Variations include oral cholecystography or cholangiography.

In oral cholecystography the patient takes a tablet containing a dye the night before the text. The dye fills the gallbladder and x-rays are used to take images of it the next day. It has been available since 1924 but has largely been replaced by ultrasound. It is more sensitive than standard x-rays, however, and may be useful in some cases for determining the structural and functional status of the gallbladder, often before nonsurgical procedures.

Cholangiography uses a dye injected into the bile duct and x-ray to view the common bile duct. It is typically used during operations to provide a clear image of the biliary tract.

Cholescintigraphy (Also Called Gallbladder Radionuclide Scan). Cholescintigraphy, a nuclear imaging technique, is more sensitive than ultrasound for diagnosing acute cholecystitis. It is noninvasive but 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.
• The patient lies on a table under a scanning camera, which detects gamma rays emitted by the dye as it passes from the liver into the gallbladder.
• The test can take up to two hours, since each image takes about a minute and they are taken every five to 15 minutes.

If the dye does not enter the gallbladder, the cystic duct is obstructed thereby indicating acute cholecystitis. The scan cannot identify individual gallstones or chronic cholecystitis. Occasionally the scan gives false positive results. (In other words, it appears to detect acute cholecystitis in people who do not have the condition.) Such results are most likely in alcoholic patients with liver disease or patients who are fasting or receiving all nutrients intravenously.

Endoscopic Retrograde Cholangiopancreatography (ERCP). Endoscopic retrograde cholangiopancreatography (ERCP) has been the gold standard for detecting common bile duct stones, particularly because they can be removed during the procedure. However, it is invasive and carries a risk for complications. With the advent of noninvasive imaging techniques, it is now generally limited to patients who have a high likelihood of common bile ducts stones and so would need them removed.

Computed Tomography. Computed tomographic (CT) scans may be a valuable additional imaging technique if the doctor suspects complicating features, such as perforation, common duct stones, or other problems such as cancer in the pancreas or gallbladder. Helical, or spiral, computed tomography (CT) scanning is advanced technique that shortens the time and obtains clearer images. With this process, the patient lies on a table that moves while a donut-like, low-radiation x-ray tube rotates around him or her.

Magnetic Resonance Imaging (MRI). MRIs may be very useful for detecting common bile duct stones, particularly a specific MRI technique called magnetic resonance cholangiography (MRC). It employs magnetic resonance imaging (MRI) and cholangiography, in which a dye is injected into the bile duct and x-rays are used to view the duct. 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. As with EUS, it is most likely to be useful in a small subset of patients and would not eliminate the need for ERCP in most patients.

Click the icon to see an image of a cholangiogram.

Virtual Endoscopy. Virtual endoscopy is an investigative technique that uses data from CT and MRI scans to generate a three-dimensional internal view of various body structures. The images resemble those used in endoscopy but the procedure is noninvasive. It one study it was able to detect smaller stones in the common bile duct than MRI. At this time it is still experimental.

Treatment

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 ("wait and see")
• 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
• Pima Native Americans
• Patients with stones larger than three centimeters

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:

• 15% likelihood of future surgery at 70 years old
• 20% at 50 years old
• 30% at 30 years old

The slight risk of developing gallbladder cancer might encourage young adults who are asymptomatic to have their gallbladders removed.

Gallstones and Severe Abdominal Pain

Gallstones are the most common cause for hospital admissions of patients with severe abdominal pain. Diagnostic tests are performed and, 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.

Gallstones and Presence of Pain (Biliary Colic) but No Infection. Patients with pain and tests that indicate gallstones but who do not show signs of inflammation or infection have the following options:

• Intravenous pain killers are administered for severe pain. Such drugs include meperidine (Demerol) or the potent NSAID ketorolac (Acular, Toradol). Ketorolac should not be used for patients who are likely to need surgery. They can cause nausea, vomiting, and drowsiness. Opioids, such as morphine, may have fewer adverse effects, but some doctors avoid them for gallbladder disease.
• They may electively choose to have the gallbladder removed (called cholecystectomy) at their convenience.
• 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. Recurrence rates are high with non-surgical options. The introduction of laparoscopic cholecystectomy has greatly reduced the use of non-surgical therapies. Note: Drugs treatments are generally inappropriate for patients who have acute gallbladder inflammation or common bile duct stones since delaying or avoiding surgery could be very hazardous in these cases.

Acute Cholecystitis (Gallbladder Inflammation). The first step if there are signs of acute cholecystitis is to "rest" the gallbladder in order to reduce inflammation. This involves the following treatments:

• Fasting.
• Intravenous fluids and oxygen therapy.
• Intravenous painkillers, usually meperidine (Demerol). Potent NSAIDs, usually indomethacin, may be particularly useful. Indomethacin, for example, can reduce pain and inflammation and improve emptying actions of the gallbladder. (Some doctors believe morphine should be avoided for gallbladder disease.)
• Intravenous antibiotics. These are administered if the patient shows signs of infection, including fever or an elevated white blood cell count, or in patients without such signs who do not improve after 12 to 24 hours.

Surgery to remove the gallbladder (called cholecystectomy) is nearly always indicated in people with acute cholecystitis. The most common procedure is now laparoscopy, a less invasive technique than open cholecystectomy (which involves a wide abdominal incision). Timing can be within hours to weeks after the acute episode, depending on the severity of the condition.

Click the icon to see an illustrated series detailing a gallbladder removal.

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

Common Duct Stones. If noninvasive diagnostic tests suggest obstruction from common duct stones, the doctor performs a procedure called endoscopic retrograde cholangiopancreatography (ERCP) to confirm the diagnosis and remove stones. This technique is used urgently along with antibiotics if infection is present in the common duct (cholangitis). (In most cases common duct stones are discovered during or after gallbladder removal.)

Surgery

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.

Open Procedures versus Laparoscopy. Until the early 1990s, open cholecystectomy (the removal of the gallbladder through a wide 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, lap choly is now used in most cholecystectomies in the United States. In fact, about 700,000 people now have their gallbladders removed each year--200,000 more than before the introduction of laparoscopy. Of concern, then, is a significant increase in its use in patients who have inflammation in the gallbladder but no infection or gallstones and in those who have gallstones but no symptoms.

Laparoscopy has largely replaced open cholecystectomy because of some significant advantage:

• The patient 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.
• It is less expensive than open cholecystectomy in the long term. The immediate treatment cost of laparoscopy may be higher than the open procedure, but the more rapid recovery with lap choly and fewer complications translate into shorter hospital stays and fewer sick days and so a greater reduction in overall costs.

Some experts believe, however, that the open procedure still 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 0.5% of open procedures, compared to about 0.3% to more than 2% with laparoscopy. (It has more overall complications than laparoscopy, however, and laparoscopy bile-duct injury rates are declining.)

The type of surgery performed on specific patients may vary depending on different factors.

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

• After a very severe gallstone attack.
• After several less severe gallstone attacks.
• After endoscopic sphincterotomy for common bile duct stones in patients with residual gallbladder stones.
• In patients with cholecystitis (gallbladder inflammation).
• In patients with pancreatitis (inflammation of the pancreas).
• In patients at risk for gallbladder cancer (e.g., patients with anomalous junction of the pancreatic and biliary ducts or patients with certain forms of porcelain gallbladder).
• In some patients with acalculous biliary pain (gallbladder disease symptoms without the presence of gallstones). Best candidates are those with evidence of impaired gallbladder emptying.

Timing of Surgery. Cholecystectomy may be performed within several days to weeks after hospitalization for an acute gallbladder attack, depending on the severity of the condition.

• Emergency gallbladder removal within 24 to 48 hours is warranted in about 20% of patients with acute cholecystitis. Indications for surgery include deterioration of the patient's condition or signs of perforation or widespread infection.
• The timing and type of surgery in patients with acute cholecystitis whose condition improves and have no signs of severe complications are under debate. Previously, the standard was open cholecystectomy between six and 12 weeks after the acute episode. Some evidence now suggests that early surgery performed between 72 and 96 hours after symptoms have lower complications than surgery performed after that.

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

• 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 long-term impact 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 the cholesterol-lowering known as statins, such as pravastatin (Pravachol), appears to lower cholesterol levels in surgical patients.

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.

• 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. (This step may raise blood pressure. The antihypertensive drug clonidine may be helpful during surgery to protect patients with high blood pressure or heart or kidney disease. Of note, a 2000 study recommended that elderly patients not receive gas. 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.
• Evidence suggests that the use of cholangiography during the operation helps prevent injury in the bile ducts, a serious complication of cholecystectomy. (Cholangiography may also used be in laparoscopy.) With this procedure, a dye is injected into the bile duct and x-rays are used to view the duct.
• In general, 24-hour monitoring afterward is not necessary and the patient can go home the same day. It should be noted, however, that according to a 2001 study some patients may be at higher risk for readmission later on, including those who required more than an hour for the operation or who had thicker gallbladder walls

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.

• Pain and fatigue are common side effects of any abdominal surgery. Patients should abstain from light recreational activities for about two days and from work and more strenuous activities for about a week.
• 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 granisteron, may prevent these effects. One study reported that patients who received a local anesthesia at the incision sites (in addition to general anesthesia) before surgery had less pain and nausea afterwards.
• Injury to the bile duct. Bile duct injury is the most serious complication of laparoscopy. It can include leakage, tears, and the development of narrowing (strictures) that can lead to liver damage. In order to minimize such injuries, some experts recommend that surgeons perform laparoscopy with a procedure called cholangiography, in which a dye is injected into the bile duct and x-rays are used to view the duct. Bile duct injury has been a more common problem than with the open procedure but increasing surgical experience and the use of cholangiography is reducing this complication and studies are now reporting more comparable rates between the two procedures.
• 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 40.) Obese patients were originally thought to be poor candidates for laparoscopic cholecystectomy, but recent research indicates that this surgery is safe for them.

Open Cholecystectomy

Before the development of 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.

Other Procedures

Percutaneous Cholecystostomy. Percutaneous cholecystostomy is a procedure that may be used in seriously ill patients with severe gallbladder infection who cannot tolerate immediate surgery. It is also the standard treatment for patients with acalculous cholecystitis (gallbladder inflammation with stones). This procedure uses a needle to withdraw (aspirate) fluid from the gallbladder. A drainage catheter is inserted through the skin and into the gallbladder while the fluid drains out. In some cases, it may be left in place for up to eight weeks. After that time, if possible, laparoscopy or an open cholecystectomy may be performed. Without a laparoscopy, recurrence rates with this procedure are high.

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.

Investigative Procedures

Mini-Laparotomy Cholecystectomy. Mini-laparotomy cholecystectomy uses small abdominal incisions but, unlike laparoscopy, it is an "open" procedure and the surgeon does not operate through a scope. The surgical instruments used are very fine caliber (2 to 3 mm in diameter, or about a tenth of an inch). Eventually this technique may reduce operative time and improve results compared to laparoscopy.

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 less than a tenth of an inch). 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:

• Fiberoptics, used to view the surgical areas, do not provide light that is as bright as light in conventional laparoscopy.
• The instruments are very fragile.
• The field of vision is very limited.

Although experience is very limited, studies are showing promise for reducing postoperative pain and improving recovery time beyond that of standard laparoscopy.

Telerobotic Surgery. In one high-tech experiment, a woman in Stasbourg, France had her gallbladder successfully removed by surgeons in New York using laparoscopy controlled by a remote robotic device. The procedure took 54 minutes and was free of complications.

Lithotripsy and Dissolution Therapies

Oral agents used to dissolve gallstones and lithotripsy alone or in combination had gained some popularity in the 1990s, but have lost favor with the increase in laparoscopy. They still may have some value in specific circumstances.

Dissolution Therapies

Oral Dissolution Therapy. Oral dissolution therapy uses bile acids in pill form to dissolve gallstones and may be used in conjunction with lithotripsy, although both techniques are rarely used at present. Ursodiol (ursodeoxycholic acid, Actigall) and chenodiol (Chenix) are the standard oral bile acid drugs used for dissolution. Most doctors 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.

Patients most likely to benefit from oral dissolution therapy are patients with small stones (less than 1.5 cm in diameter) that have a high cholesterol content.

Patients that probably will not benefit from this treatment include obese patients and those that have gallstones that are calcified or composed of bile pigments

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 doctors 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.

Investigative Agents. Fatty acid bile acid conjugates (FABACs) are experimental agents that are being investigated for dissolving gallstones and also for preventing gallstone formation.

Extracorporeal Shock Wave Lithotripsy

Gallstone fragmentation by extracorporeal shock wave lithotripsy (ESWL) may be an appropriate therapy for some patients who cannot undergo surgery but it is not commonly used anymore. 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 oral dissolution (bile acid) treatment to help dissolve the fragmented pieces of the original gallstone.

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. Elderly people may have a lower risk for recurrence than younger adults, which may make this a good choice for some.

Managing Common Bile Duct Stones

Common duct stones (choledocholithiasis) pose a high risk for complications and nearly always warrant treatment. There are various options available. It is not clear yet which one is optimal:

• 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. This required a wide abdominal incision.
• Endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic sphincterotomy (ES) is now 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 down the throat to the bile duct entrance.

• Laparoscopic cholecystectomy also is increasingly being used for detection and removal of common duct stones. This is an approach through the abdomen but uses small incisions. In such cases, it is used in combination with ultrasound or a cholangiogram (an imaging technique in which a dye is injected into the bile duct and x-rays are used to view any stones.)

Experts are currently debating the choice between laparoscopy (which is an abdominal approach) and ERCP (in which the approach uses a tube down the throat). Many surgeons believe that laparoscopy is becoming safe and effective and should be the first choice. Still, laparoscopy for common duct stones should be performed only by surgeons experienced in this new and demanding technique.

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 asked to 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 catheter (tubing) is then passed through the endoscope.
• Contrast material (a dye) is injected through the catheter 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.
• The next phase of the procedure is known as endoscopic sphincterotomy (ES). (It is also sometimes referred to as papillotomy, although this is a slightly different variation.) It 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. With ES 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).
• 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. According to 2003 studies, it is equal in effectiveness to ES but offers no advantage at this time.
• 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.

Complications. Complications of ERCP and ES occur in 5% to 8% of cases, and some can be serious, with mortality rates of 0.2% to 0.5%. They include the following:

• Pancreatitis (inflammation of the pancreas) occurs in 3% to 9% of cases and can be very serious. Younger adults are at higher risk than the elderly. The risk is also higher with more complex procedures. The drugs somatostatin or gabexate are sometimes used to reduce the risk. Gabexate appears to be more effective, although studies are mixed on whether its benefits are significant, particularly with short-term administration. (Evidence suggests that somatostatin does not reduce this 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. There is an increased risk in patients taking anti-clotting drugs and those who have cholangitis. This complication is treated by flushing the area with epinephrine.
• Perforations (rare).
• Long-term complications include stone recurrence and abscesses.

ERCP and ES are difficult procedures and patients must be certain their doctor and the medical center are experienced with them. The surgeon should have performed at least 180 ERCPs. Under such circumstances, ERCP can usually be performed successfully even in critically ill patients on mechanical ventilators.

ERCP and Gallbladder Removal (Cholecystectomy). ERCP is often performed after gallstones in the common duct are discovered during cholecystectomy (removal of the gallbladder).

In some cases, stones in the gallbladder are detected during ERCP. In such cases laparoscopic cholecystectomy is usually warranted. There is some debate about whether the gallbladder should be removed in such cases at the same time as ERCP or if patients should wait. A 2002 study suggested that immediate gallbladder removal is preferred, since the risk for recurring symptoms is very high.

Laparoscopic Exploration and Cholangiography

Surgeons are now increasingly using laparoscopy plus an imaging technique called cholangiography instead of ERCP when common duct stones are suspected.The laparoscopic procedure for common duct stones should be performed only in centers where there is expertise. It generally proceeds as follows:

• The initial approach is the same as with laparoscopic cholecystectomy. Small incisions, one or two 10 to 12 mm (around half an inch) and three 5 mm (.20 inches), are made in the abdomen.
• A tiny opening is made in the cystic duct that 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.)
• The procedure is typically used in combination with cholangiography, an imaging technique in which a dye is injected into the bile duct and x-rays are used to view any stones. Cholangiography reduces the risk for injury in the common duct.
• 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 whether the use of this procedure is better than ERCP. Many surgeons believe that laparoscopy is becoming safe and effective and should be the first choice. Still, laparoscopy for common duct stones should be performed only by surgeons experienced in this new and demanding technique.

Open Common Bile Duct Exploration (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 doctor 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 doctor 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 - 90%, although 20 - 30% of patients require more than one treatment.
• Extracorporeal Shock Wave Lithotripsy. Extracorporeal shock wave lithotripsy is an option in certain cases of bile duct stones as it is for stones in the gallbladder.

Resources

• http://digestive.niddk.nih.gov -- National Digestive Diseases Information Clearinghouse
• www.gastro.org -- American Gastroenterological Association
• www.acg.gi.org -- American College of Gastroenterology
• www.liverfoundation.org -- American Liver Foundation

References

Bellows CF, Berger DH, Crass RA. Management of gallstones. Am Fam Physician. 2005;72(4):637-642.

Cirillo DJ, Wallace RB, Rodabough RJ, Greenland P, LaCroix AZ, Limacher MC, et al. Effect of estrogen therapy on gallbladder disease. JAMA. 2005;293(3):330-339.

Dittrick GW, Thompson JS, Campos D, Bremers D, Sudan D. Gallbladder pathology in morbid obesity. Obes Surg. 2005;15(2):238-242.

Mendez-Sanchez N, Chavez-Tapia NC, Motola-Kuba D, Sanchez-Lara K, Ponciano-Rodriguez G, Baptista H, et al. Metabolic syndrome as a risk factor for gallstone disease. World J Gastroenterol. 2005;11(11):1653-1657.

Simopoulos C, Polychronidis A, Botaitis S, Perente S, Pitiakoudis M. Laparoscopic cholecystectomy in obese patients. Obes Surg. 2005;15(2):243-246.

Tsai CJ, Leitzmann MF, Hu FB, Willett WC, Giovannucci EL. A prospective cohort study of nut consumption and the risk of gallstone disease in men. Am J Epidemiol. 2004;160(10):961-968.

Tsai CJ, Leitzmann MF, Hu FB, Willett WC, Giovannucci EL. Frequent nut consumption and decreased risk of cholecystectomy in women. Am J Clin Nutr. 2004;80(1):76-81.

Tsai CJ, Leitzmann MF, Willett WC, Giovannucci EL. Dietary carbohydrates and glycaemic load and the incidence of symptomatic gall stone disease in men. Gut. 2005;54(6):823-828.

Tsai CJ, Leitzmann MF, Willett WC, Giovannucci EL. Long-term intake of trans-fatty acids and risk of gallstone disease in men. Arch Intern Med. 2005;165(9):1011-1015.

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