Gallstones and gallbladder disease
Highlights
Overview:
- Gallstones are small, hard deposits that can form in the gallbladder, a sac-like organ that lies under the liver on the right side of the abdomen.
- The process of gallstone formation (cholelithiasis) is generally slow, and usually causes no pain or other symptoms.
- The majority of gallstones are either the cholesterol or mixed type.
Risk Factors:
- Studies recently found that a mutation in the gene ABCG8 significantly increase a person's risk of gallstones. This gene controls a cholesterol pump that transports cholesterol from the liver to the bile duct.
- People with diabetes are at higher risk for gallstones, and have a higher-than-average risk for gallbladder disease without stones.
- Being overweight is a significant risk factor for gallstones.
Treatment:
- Recent studies have shown that patients with gallstone pancreatitis benefit from surgery during the initial hospitalization rather than waiting up to 2 weeks after discharge, as current guidelines recommend. Immediate surgery shortened hospital stays and prevented recurrent attacks in the weeks leading up to delayed surgery.
- The gallbladder is not an essential organ and can be safely removed.
- Laparoscopic cholecystostomy (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.
Introduction
Gallstones are small, hard deposits 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 complication.
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 - 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 down the common bile duct and 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 (such as vitamins A, D, E, and K) to pass through the intestinal lining and enter the blood stream.
Formation of Gallstones (Cholelithiasis)
The process of gallstone formation is referred to as cholelithiasis. It is generally a slow process, and usually causes no pain or other symptoms. The majority of gallstones are either the cholesterol or the mixed type. Gallstones can range in size from a few millimeters to several centimeters in diameter.
Most gallstones are formed from cholesterol. Pigment stones are also very common; they are formed from a brown-colored substance called calcium bilirubinate. Patients can have a mixture of the two types.
Cholesterol Stones. Although cholesterol makes up only 5% of bile, about three-fourths of the gallstones found in the US population are formed from cholesterol. 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 (a condition called supersaturation), which can eventually form gallstones.
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 bile becomes stagnant.
- The cells lining the gallbladder may not be able to efficiently absorb cholesterol and fat from bile.
- 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 is excreted in bile. Some experts believe it may play an important role in the formation of 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. 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 (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.
Mixed stones. Mixed stones are a mixture of cholesterol and pigment stones.
Choledocholithiasis (Common Bile Duct Stones)
Gallstones can also be present in the common bile duct, rather than the gallbladder. This condition 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. They are then called secondary stones. Secondary choledocholithiasis occurs in about 10% of patients with 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 (Acalculous Gallbladder Disease)
Gallbladder disease can occur without stones, a condition called acalculous gallbladder disease. This refers to condition where symptoms of gallbladder stones are present yet there is no evidence of stones in the gallbladder or biliary tract. It can be acute (arising suddenly) 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. Such inflammation usually results from reduced blood supply or an impairment in the gallbladder's ability to contract and empty its bile.
- Chronic acalculous gallbladder disease (also called biliary dyskinesia) appears to be caused by muscle defects or other problems in the gallbladder, which interfere with the natural movements required to empty the sac.
Symptoms
About 90% of gallstones cause no symptoms at all. If problems do occur, the chance of developing pain is about 2% per year for the first 10 years after stone formation. After 10 years, the chance for developing symptoms declines. On average, symptoms take about 8 years to develop. The reason for the decline in symptoms after 10 years is not known, although some doctors suggest that "younger," smaller stones may be more likely to cause symptoms than larger, older ones. Acalculous gallbladder disease will often present with similar symptoms to those of gallbladder stones.
Biliary Pain or Colic
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. Symptoms may be fairly nonspecific. 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 1 to several hours. If it persists beyond this point, 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 awakens 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 1- 2 attacks experienced no further biliary pain over the next 10 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-Depth Report #19 Peptic ulcers and In-Depth Report #85 Gastroesophageal reflux disease.]
Symptoms of Gallbladder Inflammation (Acute Calculous and Acalculous Cholecystitis)
Between 1 - 3% of people with symptomatic gallstones develop inflammation in the gallbladder (acute cholecystitis), which occurs when stones or sludge block 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 that is severe and constant, and may last for days. Pain frequently increases when drawing a breath.
- Pain may also 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. Acute cholecystitis can progress to gangrene or perforation of the gallbladder if left untreated. Infection develops in about 20% of acute cholecystitis, which increases the danger from this condition. 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; these are the most common symptoms, but they may be vague and indistinguishable from similar complaints in people without gallbladder disease.
- Chronic diarrhea (4 - 10 bowel movements every day for at least 3 months).
Symptoms of Stones in the Common Bile Duct (Choledocholithiasis)
Stones lodged in the common bile duct can cause symptoms that are similar to those produced by stones that lodge in the gallbladder, but they may also cause the following symptoms:
- 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 and Complications
Asymptomatic gallstones seldom lead to problems. Death, even from symptomatic gallstones, is very rare. Serious complications are also rare. If they do occur, complications 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 (acute cholecystitis), or both.
- About 10% of patients with symptomatic gallstones also have stones that pass into and obstruct the common bile duct (choledocholithiasis).
Infections
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 (a condition called septicemia), and surgery is often required. Symptoms include fever, rapid heartbeat, fast breathing, and 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. Inflammation can also cause necrosis (destruction of tissue in the gallbladder), which leads to gangrene. 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 acute cholecystitis cases result in a perforated gallbladder, which is a life-threatening condition. In general, this occurs in people who wait too long to seek help, or in people who do not respond to treatment. Perforation of the gallbladder 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, pain may temporarily decrease. This is a dangerous and misleading event, however, since peritonitis (widespread abdominal infection) develops afterward.
- Empyema. Pus in the gallbladder (empyema) occurs in 2 - 3% of patients with acute cholecystitis. Patients usually experience severe abdominal pain for more than 7 days. The physical exam often fails to reveal the underlying cause. The condition can be life-threatening, particularly if 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 (channel) between the organs develops. Sometimes, in these cases, gallstones can actually pass into the small intestine, which can be very serious and requires immediate surgery.
- Gallstone Ileus. A gallstone blocking the intestine is known as gallstone ileus. It primarily occurs in patients over age 65, and can sometimes be fatal. Depending on where the stone is located, surgery to remove the stone may be required.
- Infection in the Common Bile Duct (Cholangitis). Infection in the common bile duct (cholangitis) from obstruction is common and serious. 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. 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
- Pancreatitis. Common bile duct stones are 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.
Other Complications
Gallbladder cancer: Gallstones are present in about 80% of people with gallbladder cancer. There is a strong association between gallbladder cancer and cholelithiasis, chronic cholecystitis, and inflammation. Symptoms of gallbladder cancer usually do not appear 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 beyond the mucosa (the inner lining), removal of the gallbladder results in a 5-year survival rate of 68%. If cancer has spread to deeper layers, more extensive surgery or other treatments may be required.
This cancer is very rare, even among people with gallstones. Certain conditions in the gallbladder, however, pose a higher than average risk for this cancer.
Gallbladder Polyps. 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 - 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 - 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 congenital condition, the junction of the common bile duct and main pancreatic duct is located outside the wall of the small intestine and forms a long channel between the two ducts. This problem poses a very high risk of cancer 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 of cancer, although recent evidence suggests that the risk is lower than previously thought. This condition may develop from a chronic inflammatory reaction that may actually be responsible for the cancer risk. The cancer risk appears to depend on the presence of specific factors, such as partial calcification involving the inner lining of the gallbladder.
Risk Factors
About 20 million Americans harbor gallstones. Only 1 - 3% of the population, however, complains of symptoms during the course of a year, and fewer than half of these people will have recurrent symptoms.
Risk Factors in Women
Women are much more likely than men to develop gallstones. Gallstones occur in nearly 25% of women in the U.S. by age 60 and as many as 50% by age 75. 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 if possible. In fact, gallstones may disappear after delivery. If surgery is necessary, 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. 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 age 75. 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 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 U.S. 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 Indian females in Chile and Peru develop gallstones. 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 one-third of cases of painful gallstones may be related to genetic factors.
Studies recently found that a mutation in the gene ABCG8 significantly increase a person's risk of gallstones. This gene controls a cholesterol pump that transports cholesterol from the liver to the bile duct. It appears this mutation may cause the pump to continuously work at a high rate.
Defects in transport proteins involved in biliary lipid secretion appear to predispose certain people to gallstone disease, but this alone many not be sufficient to create gallstones. Studies indicate that the disease is complex and may result from the interaction between genetics and environment. Some studies suggest immune and inflammatory mediators may play key roles.
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.
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.
Weight Cycling. Rapid weight loss or cycling (dieting and then putting weight back on) further increases cholesterol production in the liver, with resulting supersaturation and risk for gallstones.
- The risk for gallstones is as high as 12% after 8 -16 weeks of restricted-calorie diets.
- The risk is more than 30% within 12 - 18 months after gastric bypass 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 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. Men are also at increased risk for developing gallstones when their weight fluctuates. The risk increases proportionately with dramatic weight changes as well as with frequent weight cycling.
Bariatric Surgery. Patients who have either Roux-en-Y or laparoscopic banding bariatric surgery are at increased risk for gallstones. For this reason, many centers request the patient undergo cholecystectomy before their bariatric procedure. However, doctors are now questioning this practice.
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 is associated with low levels of "good" HDL cholesterol and high triglyceride levels. Some evidence suggests that high levels of triglycerides may impair the 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. [For more information, 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. Up to 40% of patients on home intravenous nutrition develop gallstones, and the risk may be higher in patients on total intravenous nutrition. It is suspected that the cause is lack of stimulation in the gut, since patients who also take some food by mouth have less risk of developing gallstones. However, treatment for gallstones in this population is associated with a low risk of complications.
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 age 60 and those who have had numerous bowel operations (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 of gallstones. The complications can be so severe that some organ transplant centers require the patient's gallbladder be removed before the transplant is performed.
Medications. Octreotide (Sandostatin) poses a risk for gallstones. In addition, 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.
Heme Iron. High consumption of heme iron, the type of iron found in meat and seafood, has been shown to lead to gallstone formation in men. Gallstones are not associated with diets high in non-heme iron foods such as beans, lentils, and enriched grains.
Prevention
Diet may play a role in gallstones. Following are some observations on specific dietary factors.
Fats. Although fats (particularly saturated fats found in meats, butter, and other animal products) have been associated with gallstone attacks, some studies 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 fish oil). Fish oil may be particularly beneficial in patients with high triglyceride levels, because it improves 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 and tree nuts, such as walnuts and almonds).
Fruits and Vegetables. Researchers who followed more than 77,000 healthy women for 16 years in the Nurses' Health Study found that those who ate the most fruits and vegetables had the lowest risk of developing symptomatic gallstones that required removal of the gallbladder. The effect was consistent regardless of which fruits or vegetables they ate.
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. 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 such as pasta and bread can also increase risk, since carbohydrates are converted to sugar in the body.
Alcohol. A few studies have reported a lower risk for gallstones with alcohol consumption. Even small amounts (1 ounce per day) have been found to reduce the risk of gallstones in women by 20%. Moderate intake (defined as 1 - 2 drinks a day) also appears to have heart protection 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.
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. A promising 2001 study suggested that orlistat (Xenical), a drug for treating obesity, may protect against gallstone formation during weight loss. The drug appeared to reduce bile acids and other components involved in gallstone production.
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 verify that abdominal pain is caused by stones and not by some other condition. Ultrasound or other imaging techniques can usually detect gallstones. 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 any number of 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. However, the pain of IBS 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 the 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) based on classic symptoms (constant and severe pain in the upper right quadrant of the abdomen). Imaging techniques are necessary to confirm the 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:
- Bilirubin and the enzyme alkaline phosphatase are usually elevated in acute cholecystitis, and especially choledocholithiasis (common bile duct stones). Bilirubin is the orange-yellow pigment found in bile. High levels of bilirubin cause jaundice, which gives the skin a yellowish tone.
- Levels of 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.
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 6 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 2 mm in diameter with an accuracy of 90 - 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.
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 test. The dye fills the gallbladder, and x-ray images are taken the next day. The test 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.
In cholangiography, a dye is injected into the bile duct and x-rays are used to view the duct. It is typically used during operations to provide a clear image of the biliary tract.
Cholescintigraphy (Also Called Gallbladder Radionuclide Scan or HIDA scan). Cholescintigraphy, a nuclear imaging technique, is more sensitive than ultrasound for diagnosing acute cholecystitis. It is noninvasive but can take 1 - 2 hours or 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 (radioactive) rays emitted by the dye as it passes from the liver into the gallbladder.
- The test can take up to 2 hours, since each image takes about a minute, and they are taken every 5 -15 minutes.
If the dye does not enter the gallbladder, the cystic duct is obstructed, indicating acute cholecystitis. The scan cannot identify individual gallstones or chronic cholecystitis.
Occasionally, the scan gives false positive results (detecting acute cholecystitis in people who do not have the condition). Such results are most common in alcoholic patients with liver disease or patients who are fasting or receiving all their nutrition 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, ERCP is now generally limited to patients who have a high likelihood of common bile ducts stones, which would need to be removed. It may also be used to diagnose biliary dyskinesia.
Computed Tomography. Computed tomography (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 (spiral) CT scanning is advanced technique that shortens the time and obtains clearer images. With this process, the patient lies on a table while a donut-like, low-radiation x-ray tube rotates around the patient.
Magnetic Resonance Imaging (MRI). MRI, particularly a specific MRI technique called magnetic resonance cholangiography (MRC), may be very useful for detecting common bile duct stones,. MRC employs 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 experimental technique that uses data from CT and MRI scans to generate a 3-dimensional view of various body structures. The images resemble those used in endoscopy (an invasive procedure), but the procedure is noninvasive. In one study virtual endoscopy was able to detect smaller stones in the common bile duct than MRI.
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 3 approaches to gallstone treatment:
- Expectant management ("wait and see")
- Nonsurgical removal of the stones
- Surgical removal of the gallbladder
Expectant Management of Asymptomatic Gallstones
Guidelines from the American College of Physicians state that when a person has no symptoms, the risks of both surgical and nonsurgical treatments for gallstones outweigh the benefits. Experts suggest a wait-and-see approach, which they have termed expectant management, for these patients. Exceptions to this policy are people at risk for complications from gallstones, including the following:
- Those at risk for gallbladder cancer
- Pima Native Americans
- Patients with stones larger than 3 cm
One study reported that very small gallstones increase the risk for acute pancreatitis, a serious condition. Some experts therefore believe that gallstones smaller than 5 mm 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 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 age 70
- 20% at age 50
- 30% at age 30
The slight risk of developing gallbladder cancer might encourage young adults who are asymptomatic to have their gallbladders removed.
Symptomatic patients
Gallstones are the most common cause for hospital admissions of patients with severe abdominal pain. Many other patients experience milder symptoms. Results of diagnostic tests and clinical presentation will guide the treatment, 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 do not show signs of inflammation or infection have the following options:
- Intravenous painkillers for severe pain. Such drugs include meperidine (Demerol) or the potent NSAID ketorolac (Toradol). Ketorolac should not be used for patients who are likely to need surgery. These drugs can cause nausea, vomiting, and drowsiness. Opioids such as morphine may have fewer adverse effects, but some doctors avoid them in gallbladder disease.
- Elective gallbladder removal. Patients may electively choose to have their gallbladder removed (called cholecystectomy) at their convenience.
- Lithotripsy. 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 2 cm in diameter.
- Drug therapy. 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 nonsurgical options, and the introduction of laparoscopic cholecystectomy has greatly reduced the use of nonsurgical therapies. Note: Drug treatments are generally inappropriate for patients who have acute gallbladder inflammation or common bile duct stones, since delaying or avoiding surgery could be life-threatening.
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
- Strong painkillers, such as meperidine (Demerol). Potent NSAIDs, such as ketorolac, may also be particularly useful. 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 - 24 hours.
Surgery to remove the gallbladder is nearly always indicated in people with acute cholecystitis. The most common procedure now is laparoscopy, a less invasive technique than open cholecystectomy (which involves a wide abdominal incision). Surgery may be done 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-associated pancreatitis almost always require surgery with either laparoscopic or open cholecystectomy.
Recent studies have shown that surgery during the initial hospital admission for gallstone pancreatitis is better for patients, rather than waiting up to 2 weeks after discharge, as current guidelines recommend. Patients who have had immediate surgery (when possible) required shorter hospital stays. Patients who had delayed surgery experienced a high rate of recurrent attacks before their surgery. Complications rates were the same in both groups.
Common Duct Stones. If noninvasive diagnostic tests suggest obstruction from common duct stones, the doctor will perform 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.
Management of Common Bile Duct Stones
Common bile duct stones pose a high risk for complications and nearly always warrant treatment. There are various options available. It is not clear yet which one is best.
- 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 procedure for detecting and managing common bile 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 bile duct stones. This is an approach through the abdomen, but it uses small incisions instead of one large incision. It is used in combination with ultrasound or a cholangiogram (an imaging technique in which a dye is injected into the bile duct and moving x-rays are used to view any stones).
Experts are currently debating the choice between laparoscopy and ERCP. Many surgeons believe that laparoscopy is becoming safe and effective and should be the first choice. Still, laparoscopy for common bile duct stones should be performed only by surgeons experienced in this technique.
Dissolution Therapies
Oral agents used to dissolve gallstones and lithotripsy (alone or in combination with other drugs) had gained some popularity in the 1990s. But these oral agents have lost favor with the increased use of laparoscopy. They may still have some value in specific circumstances.
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, Actigal, UDCAl) and chenodiol (Chenix) are the standard oral bile acid dissolution drugs. Most doctors prefer ursodeoxycholic acid, which is considered to be among the safest of common drugs. 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 those with small stones (less than 1.5 cm in diameter) that have a high cholesterol content.
Patients who probably will not benefit from this treatment include obese patients and those with gallstones that are calcified or composed of bile pigments
Only about 30% of patients are candidates for oral dissolution therapy; the number may actually be much lower, since compliance is often a problem. The treatment can take up to 2 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 5 - 12 hours. Serious side effects include severe burning pain.
Surgery
The gallbladder is not an essential organ, and its removal is one of the most common surgical procedures performed on women. It can even be performed on pregnant women with low risk to the baby and the mother. The primary advantages of surgical removal of the gallbladder over nonsurgical treatment are elimination of gallstones and 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 it offers some significant advantages:
- The patient can leave the hospital and resume normal activities earlier, compared to open surgery.
- The incisions are small, and there is less postoperative 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 therefore 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 - 0.5% of open procedures, compared to about 0.3 - 2% with laparoscopy. Open surgery has more overall complications than laparoscopy, however, and bile-duct injury rates with laparoscopy 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, or have had, one of the following conditions:
- A very severe gallstone attack
- Several less severe gallstone attacks
- Endoscopic sphincterotomy for common bile duct stones (in patients with residual gallbladder stones)
- Cholecystitis (gallbladder inflammation).
- Pancreatitis (inflammation of the pancreas)
- High risk for gallbladder cancer (such as patients with anomalous junction of the pancreatic and biliary ducts or patients with certain forms of porcelain gallbladder)
- Acalculous biliary pain (gallbladder disease symptoms without the presence of gallstones). The best candidates are those with evidence of impaired gallbladder emptying.
Pregnant women who have gallstones and experience symptoms are also candidates for surgery.
Timing of Surgery. Cholecystectomy may be performed within days to weeks after hospitalization for an acute gallbladder attack, depending on the severity of the condition.
- Emergency gallbladder removal within 24 - 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 6 - 12 weeks after the acute episode. Some evidence now suggests that early surgery performed between 72 - 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 0.7 - 2%.)
- Emergency cholecystectomy carries a much higher mortality rate (as high 19% in ill elderly patients).
Long-Term Effects of Gallbladder Removal. Removal of the gallbladder has not been known to cause any long-term adverse effects aside from occasional diarrhea.
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 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.
- One or two 10 - 12 mm (about one-half inch) and three 5 mm (about a fifth of an inch) incisions 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. With this procedure, dye is injected into the bile duct, and moving x-rays are used to view the duct.
- In general, the patient can go home the same day, although those whose operation took longer than 1 hour, or who had thicker gallbladder walls, may be at somewhat higher risk of complications from early discharge.
Risk Factors for Conversion from Laparoscopy to an Open Procedure. In about 5 - 10% of laparoscopies, conversion to open cholecystectomy is required during the procedure. The rate of conversion to open surgery is higher in men than in women. This may be due to the higher rate of inflammation and fibrosis in men with symptomatic gallstones. Other reasons for conversion from laparoscopic to open surgery include:
- 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.
- Previous endoscopic sphincterotomy
- A thickened gallbladder wall
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 2 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 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 cholangiography Bile duct injury has been a more common problem in laparoscopy compared to the open procedure, but increasing surgical experience and the use of cholangiography is reducing this complication. Studies are now reporting more comparable rates between the two procedures.
- In about 6% of procedures, the surgeon misses some gallstones, or they spill 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 (the minimum should be 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 large surgical scar. In this procedure, the patient usually stays in the hospital for 5 - 7 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 the need to explore the common bile duct for stones at the same time.
Candidates for whom cholecystectomy may be a more appropriate choice:
- Patients who have had extensive previous abdominal surgery
- Patients with complications of acute cholecystitis (empyema, gangrene, perforation of the gallbladder).
Older patients. Those over 80 are likely to have lower complication rates from open cholecystectomy than laparoscopy, although laparoscopy may also be appropriate in these patients.
Whether or not to insert a drain in the wound after surgery is under debate. Many surgeons implant drains primarily to prevent abscess or peritonitis. That practice may change. A recent analysis of all randomized clinical trials comparing drains versus no drains, or the type of drain used found that patients who received drains had a dramatically increased risk of wound and chest infection. The type of drain used made no difference.
ERCP with Endoscopic Sphincterotomy (ES)
Reasons for performing the procedure:
- Before gallbladder surgeries, when there is strong suspicion that common bile duct stones are present.
- After gallbladder surgeries in which the surgeon detects stones in the common bile duct (only if there are experts in ERCP present, and equipment is available).
- For patients with gallstone cholangitis (serious infection in the common bile duct). In such cases urgent ERCP and antibiotics are required.
- When acute pancreatitis is caused by gallstones. In such cases urgent ERCP and antibiotics are required. (The use of ERCP 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 ERCP intervention. In a 2000 analysis of four studies, however, ERCP significantly improved survival rates and reduced complications in patients.)
The ERCP and ES Procedure. A typical ERCP and endoscopic 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 fiber optics 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 sensation of bloating.
- 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 x-ray visualization 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.) ES widens the junction between the common bile duct and intestine (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 (the sphincter of Oddi).
- One recent alternative to ES is the use of a small inflatable balloon (a procedure known as endoscopic balloon dilation) that opens up the ampulla of Vater to allow stones to pass. This variation does not involve cutting 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 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 - 8% of cases, and some can be serious, with mortality rates of 0.2 - 0.5%. They include the following:
- Pancreatitis (inflammation of the pancreas) occurs in 3 - 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, although recent evidence suggests somatostatin may not actually reduce this risk. Gabexate appears to be more effective, although studies are mixed on whether its benefits are significant, particularly with short-term treatment.
- Postoperative 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 for bleeding 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 have experience 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.
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.
Open or Laparoscopic Common Bile Duct Exploration (Choledocholithotomy)
Laparoscopic Exploration and Cholangiography
Surgeons are now increasingly using laparoscopy with cholangiography instead of ERCP when common duct stones are suspected. Laparoscopy with cholangiography should only be done in centers with expertise in this procedure. Potential indications include.
- An alternative to ERCP before gallbladder surgeries, when there is high suspicion of common bile duct stones.
- During gallbladder surgeries when common duct stones are detected or highly suspected.
The procedure usually involves the following steps:
- The initial approach is the same as with laparoscopic cholecystectomy. Small incisions, one or two 10 - 12 mm (around half an inch) and three 5 mm (about a fifth of an inch), 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 cholangiography. Cholangiography also reduces the risk for injury in the common duct.
- If stones are identified, the surgeon inserts a tube with an inflatable balloon 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, ERCP or open surgery is performed.
Experts are debating whether this procedure is better than ERCP. Many surgeons believe that laparoscopy is becoming safe and effective, and should be the first choice of treatment. 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
- When the duct anatomy is complex
- During or after some gallbladder operations when stones are detected. If the procedure is laparoscopy, surgeon may convert to open procedure, though this happens less often now.
- When ERCP or laparoscopic procedures are not available.
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 7 - 10 days after surgery, to determine if any stones remain in the duct.
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 no longer widely used. 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 treatment to help dissolve the fragmented pieces of the original gallstone.
Complications. 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, which can be 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.
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 without stones). This procedure uses a needle to aspirate (withdraw fluid) from the gallbladder. A drainage catheter is inserted through the skin and into the gallbladder while the fluid drains out. In some cases, the catheter may be left in place for up to 8 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 leaving a catheter in the abdomen afterward, and may have fewer complications than percutaneous cholecystostomy.
Investigative Procedures
Mini-Laparotomy Cholecystostomy. Mini-laparotomy cholecystostomy 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 small (2 - 3 mm in diameter, or about a tenth of an inch). Eventually, this technique may reduce operative time and enable surgeons to obtain better results than with laparoscopy.
Needlescopic Cholecystostomy. 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 (2 - 3) and smaller ones (1.2 - 3 mm, or less than one-tenth of an inch). It should be noted, however, that these procedures still require one larger incision (10 - 12 mm, or about one-half 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 the light used 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, surgeons in New York removed the gallbladder of a woman in France in a laparoscopic procedure using tools controlled by a remote robotic device. The procedure took 54 minutes and was free of complications.
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
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Reviewed By: Reviewed by: Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.
