Gallstones

• Gallstones are "stones" that form in the gallbladder or bile ducts. The common types of gallstones are cholesterol, black pigment, and brown pigment.
• The most common symptoms of gallstones are biliary colic and cholecystitis; however, usually, gallstones cause no symptoms.
• The pain from biliary colic is a very specific type that comes on suddenly or rapidly and builds to a peak over a few minutes; however, the pain may vary in severity. The movement does not make the pain worse.
• Other signs and symptoms of biliary colic include:
  • Nausea
  • Pain commonly felt in the upper abdomen
  • Rarely, pain may be felt under the sternum and is mistaken for a heart attack or angina (chest pain).
  • Biliary colic usually has a pattern that varies from person to person.
• Gallstones do not cause intolerance to fatty foods, belching, abdominal distention, or gas.
• Complications of gallstones include cholangitis, gangrene of the gallbladder, jaundice, pancreatitis, sepsis, fistula, and ileus.
• Gallbladder sludge is associated with symptoms and complications of gallstones; however, like gallstones, sludge usually does not cause problems.
• The best single test for diagnosing gallstones is transabdominal ultrasonography. Other tests include endoscopic ultrasonography, magnetic resonance cholangiopancreatography (MRCP), cholescintigraphy (HIDA scan), endoscopic retrograde cholangiopancreatography (ERCP), liver and pancreatic blood tests, duodenal drainage, oral cholecystogram (OCG), and intravenous cholangiogram (IVC).
• Gallstones are managed primarily with observation (no treatment) or removal of the gallbladder (cholecystectomy). Less commonly used treatments include sphincterotomy and extraction of gallstones, dissolution with oral medications, and extracorporeal shock-wave lithotripsy (ESWL). Prevention of cholesterol gallstones also is possible with oral medications.
• Symptoms of gallstones should stop the following cholecystectomy. If they do not, it is likely that gallstones were left in the ducts, there is a second problem within the bile ducts, or the symptoms are caused by another problem.
• Many dietary recommendations have been made for the prevention or treatment of gallstones and to prevent their symptoms, but none of them have been shown to be effective.
• Many home remedies have been suggested for eliminating gallstones, but none have been shown to be effective
• Continuing research is directed at uncovering the genes that are responsible for the formation of gallstones.

Gallstones (often misspelled as gall stones) are stones that form in the gall (bile) within the gallbladder. (The gallbladder is a pear-shaped organ just below the liver that stores bile secreted by the liver.) Gallstones reach a size of between a sixteenth of an inch and several inches.

• Bile is a watery liquid made by the cells of the liver that is important for digesting food in the intestine, particularly fat, and eliminating toxic substances from the body.
• Liver cells secrete the bile into small canals within the liver referred to as canaliculi.
• The bile flows through the canaliculi and into larger collecting ducts within the liver referred to as intrahepatic bile ducts.
• The bile then flows through merged intrahepatic bile ducts out of the liver as extrahepatic (outside the liver) bile ducts, ( first into the two hepatic bile ducts, then into the single common hepatic duct, and finally, after the common hepatic duct is joined by the cystic duct coming from the gallbladder, into the common bile duct.

From the bile duct, bile can flow from two different directions.

• The first direction is through the common bile duct and directly into the intestine where the bile mixes with food and promotes digestion of food. At the same time, toxic substances that are removed by the liver from the blood are eliminated into the intestine.
• The second direction is into an offshoot of the common bile duct, the cystic duct, and from there into the gallbladder.

Once in the gallbladder, bile is concentrated by the removal (absorption) of water. During a meal, the muscle that makes up the wall of the gallbladder contracts and squeezes the concentrated bile in the gallbladder back through the cystic duct into the common bile duct and then into the intestine. (Concentrated bile is much more effective for digestion than the un-concentrated bile that goes from the liver straight into the intestine.) The timing of gallbladder contraction - during a meal - allows the concentrated bile from the gallbladder to mix with food.

Gallstones usually form in the gallbladder; however, they also may form anywhere there is bile - in the intrahepatic, hepatic, common bile, and cystic ducts.

Gallstones also may move about in the bile, for example, from the gallbladder into the cystic or the common duct.

The majority of people with gallstones have no signs or symptoms and are unaware of their gallstones. (The gallstones are "silent.") These gallstones often are found as a result of tests (for example, ultrasound, or X-rays of the abdomen) performed while evaluating medical conditions other than gallstones. Symptoms can appear later in life, however, after many years without symptoms. Thus, over a period of five years, approximately 10% of people with silent gallstones will develop symptoms. Once symptoms develop, they are likely to continue and often will worsen.

When signs and symptoms of gallstones occur, they virtually always occur because the gallstones obstruct the bile ducts.

The most common symptom of gallstones is biliary colic. Biliary colic is a very specific type of pain, occurring as the primary or only symptom in 80% of people with gallstones who develop symptoms. Biliary colic occurs when the bile ducts (cystic, hepatic ducts, or common bile ducts) are suddenly blocked by a gallstone. Slowly progressing obstruction, as from a tumor, does not cause biliary colic. Behind the obstruction, fluid accumulates and distends the ducts and gallbladder. In the case of hepatic duct or common bile duct obstruction, this is due to continued secretion of bile by the liver. In the case of cystic duct obstruction, the wall of the gallbladder secretes fluid into the gallbladder. The distention of the ducts or gallbladder causes biliary colic.

Characteristically, biliary colic comes on suddenly or builds rapidly to a peak over a few minutes.

• It is a constant pain; it does not come and go, though it may vary in intensity while it is present. IT is not cramp-like.
• It lasts for 15 minutes to 4-5 hours. If the pain lasts more than 4-5 hours, it means that a complication - usually cholecystitis - has developed.
• The pain usually is severe, but the movement does not make the pain worse. In fact, patients experiencing biliary colic often walkabout or writhe (twist the body in different positions) in bed trying to find a comfortable position.
• Biliary colic often is accompanied by nausea.
• Most commonly, biliary colic is felt in the middle of the upper abdomen just below the sternum.
• The second most common location for pain is the right upper abdomen just below the margin of the ribs.
• Occasionally, the pain also may be felt in the back at the lower tip of the scapula on the right side.
• On rare occasions, the pain may be felt beneath the sternum and is mistaken for angina or a heart attack.
• An episode of biliary colic subsides gradually once the gallstone shifts within the duct so that it is no longer causing an obstruction.

Biliary colic is a recurring symptom. Once the first episode occurs, there are likely to be other episodes. Moreover, there is a pattern of recurrence for each individual, that is, in some individuals, the episodes tend to remain frequent while in others they are infrequent. The majority of people who develop biliary colic do not go on to develop cholecystitis or other complications. There is a misconception that contraction of the gallbladder is what causes the obstruction of the ducts and biliary colic. Eating, even fatty foods, does not cause biliary colic; most episodes of biliary colic occur during the night, long after the gallbladder has emptied.

Gallstones are blamed for many symptoms they do not cause. Among the symptoms gallstones do not cause are:

• dyspepsia (including abdominal bloating and discomfort after eating),
• intolerance to fatty foods,
• belching, and
• flatulence (passing gas or farting).

Removal of the gallbladder (cholecystectomy) should eliminate all gallstone-related symptoms except in three situations:

1. gallstones were left in the ducts,
2. there were problems with the bile ducts in addition to gallstones, and
3. gallstones were not the cause of the symptoms.

The possibility of gallstones in the ducts can be pursued with MRCP, endoscopic ultrasound, and ERCP. Rarely, gallstone-like symptoms can be caused by a condition called sphincter of Oddi dysfunction, discussed below.

The common bile duct has a muscular wall. The last several centimeters of the common bile duct's muscle immediately before the duct joins the duodenum comprise the sphincter of Oddi. The sphincter of Oddi controls the flow of bile. Since the pancreatic duct usually joins the common bile duct shortly before it enters the duodenum, the sphincter also controls the flow of fluid from the pancreatic duct. When the muscle of the sphincter tightens, it shuts off the flow of bile and pancreatic fluid. When it relaxes, bile and pancreatic fluid again flow into the duodenum, for example, after a meal. The sphincter may become scarred, and the duct is narrowed by the scarring. (The cause of the scarring is unknown.) The sphincter also may go into spasm intermittently. In either case, the flow of bile and pancreatic fluid may intermittently stop abruptly, mimicking the effects of a gallstone causing biliary colic and pancreatitis.

The diagnosis of sphincter of Oddi dysfunction can be difficult to make. The best diagnostic test requires an endoscopic procedure with the same type of endoscope as ERCP. Instead of filling the ducts with dye, however, the pressure within the sphincter is measured. If the pressure is abnormally high, scarring or spasm of the sphincter are likely. The treatment for sphincter of Oddi dysfunction is sphincterotomy (described previously). The measurement of liver and pancreatic enzymes in the blood also may be useful in diagnosing sphincter dysfunction.

Gallstones may number anywhere from one to hundreds, varying in size from a millimeter to four or five centimeters. When there are single or only a few gallstones they tend to be round. When larger numbers of gallstones are present, they tend to be faceted due to the rubbing of one gallstone against another. Brown pigment gallstones may be crumbly and irregular.

Do gallstones pass?

Gallstones may pass out of the gallbladder or ducts particularly if they are small. It is the passage of gallstones that leads to many of their complications.

Gallstones are common; they occur in approximately 20% of women in the US, Canada and Europe, but there is a large variation in the prevalence among different ethnic groups. For example, gallstones occur 1 ½ to 2 times more commonly in Scandinavians and Mexican-Americans. Among American Indians, gallstone prevalence is more than 80%. These differences probably are accounted for by genetic (hereditary) factors. First-degree relatives (parents, siblings, and children) of individuals with gallstones are 1 ½ times more likely to have gallstones than if they do not have a first-degree relative with gallstones. Further support for a genetic predisposition comes from twin studies. Thus, among non-identical pairs of twins (who share 50% of their genes with one another), both individuals in a pair have gallstones 8% of the time. Among identical pairs of twins (who share 100% of their genes with one another), both individuals have gallstones 23% of the time.

Several conditions are associated with the formation of gallstones, and the way in which they cause gallstones can vary. (See risks of gallstones.)

There are several types of gallstones, and each type has a different cause.

Cholesterol gallstones

Cholesterol gallstones are primarily made up of cholesterol. They are the most common type of gallstone, comprising 80% of gallstones in individuals in Europe and the Americas. Cholesterol is one of the substances (chemicals) that liver cells secrete into bile. Secretion of cholesterol into bile is an important mechanism by which the liver eliminates excess cholesterol from the body.

In order for bile to carry cholesterol, the cholesterol must be dissolved in the bile. Cholesterol is fat, however, and bile is an aqueous or watery solution; fats do not dissolve in watery solutions. In order to make the cholesterol dissolve in bile, the liver also secretes two detergents, bile acids, and lecithin, into the bile. These detergents, just like dishwashing detergents, dissolve the fatty cholesterol so that it can be carried by bile through the ducts. If the liver secretes too much cholesterol for the number of bile acids and lecithin it secretes, some of the cholesterol does not stay dissolved. Similarly, if the liver does not secrete enough bile acids and lecithin, some of the cholesterol does not stay dissolved. In either case, the undissolved cholesterol sticks together and forms particles of cholesterol that grow in size and eventually become gallstones.

Two other processes promote the formation of cholesterol gallstones though neither process is able to cause cholesterol gallstones to form.

• The first is an abnormally rapid formation and growth of cholesterol particles into gallstones. Thus, with the same concentrations of cholesterol, bile acids, and lecithin in the bile, patients with gallstones form particles of cholesterol more rapidly than individuals without gallstones.
• The second process that promotes the formation and growth of gallstones is reduced contraction and emptying of the gallbladder that allows bile to stay in the gallbladder longer than normal so that there is more time for cholesterol particles to form and grow into gallstones.

Pigment gallstones

Pigment gallstones are the second most common type of gallstone. Although pigment gallstones comprise only 15% of gallstones in individuals from Europe and the Americas, they are more common than cholesterol gallstones in Southeast Asia. There are two types of pigment gallstones 1) black pigment gallstones, and 2) brown pigment gallstones.

The pigment is a waste product formed from hemoglobin, the oxygen-carrying chemical in red blood cells. The hemoglobin from old red blood cells that are being destroyed is changed into a chemical called bilirubin and released into the blood. Bilirubin is removed from the blood by the liver. The liver modifies the bilirubin and secretes the modified bilirubin into bile so that it can be eliminated from the body.

Black pigment gallstones: If there is too much bilirubin in the bile, the bilirubin combines with other constituents in bile, for example, calcium, to form pigment (so-called because it is dark brown in color). Pigment dissolves poorly in bile and, like cholesterol, it sticks together and forms particles that grow in size and eventually become gallstones. The pigment gallstones that form in this manner are called black pigment gallstones because they are black and hard.

Brown pigment gallstones: If there is a reduced contraction of the gallbladder or obstruction to the flow of bile through the ducts, bacteria may ascend from the duodenum into the bile ducts and gallbladder. The bacteria alter the bilirubin in the ducts and gallbladder, and the altered bilirubin then combines with calcium to form pigment. The pigment then combines with fats in bile (cholesterol and fatty acids from lecithin) to form particles that grow into gallstones. This type of gallstone is called a brown pigment gallstone because it is more brown than black. It also is softer than black pigment gallstones.

Other types of gallstones. Other types of gallstones are rare. Perhaps the most interesting type is the gallstone that forms in patients taking the antibiotic, ceftriaxone (Rocephin). Ceftriaxone is unusual in that it is eliminated from the body in bile in high concentrations. It combines with calcium in bile and becomes insoluble. Like cholesterol and pigment, the insoluble ceftriaxone and calcium form particles that grow into gallstones. Fortunately, most of these gallstones disappear once the antibiotic is discontinued; however, they still may cause problems until they disappear. Another rare type of gallstone is formed from calcium carbonate.

Risk for cholesterol gallstones

There is no relationship between cholesterol in the blood and cholesterol gallstones. Individuals with elevated blood cholesterol do not have an increased prevalence of cholesterol gallstones. A common misconception is that diet is responsible for the development of cholesterol gallstones, however, it isn't. The eight risk factors for developing cholesterol gallstones include:

1. Gender. Gallstones occur more commonly in women than men.
2. Age. Gallstone prevalence increases with age.
3. Obesity. Obese individuals are more likely to form gallstones than thin individuals.
4. Pregnancy. Pregnancy increases the risk for cholesterol gallstones because, during pregnancy, bile contains more cholesterol, and the gallbladder does not contract normally. This change in the composition of bile during pregnancy is due to the hormonal changes that occur during pregnancy. Gallstones that form during pregnancy may remain following the pregnancy or may dissolve once the composition of bile has returned to the nonpregnant state.
5. Birth control pills and hormone therapy Increased levels of hormones caused by either treatment mimics pregnancy.
6. Rapid weight loss. Rapid weight loss by whatever means, whether it is a very low-calorie diet or obesity surgery, causes cholesterol gallstones in up to 50% of individuals. Many of the gallstones will disappear after the weight is lost, but many do not. Moreover, until they are gone, they may cause problems.
7. Crohn's disease. Individuals with Crohn's disease of the ileum are more likely to develop gallstones. Gallstones form because patients with Crohn's disease lack enough bile acids to solubilize the cholesterol in bile. Normally, bile acids that enter the small intestine from the liver and gallbladder are absorbed back into the body and are secreted again by the liver into bile. In other words, the bile acids recycle. In Crohn's disease, the ileum is diseased. Bile acids are not absorbed normally, the body becomes depleted of bile acids, and fewer bile acids are secreted in bile. As a result, there are not enough detergent bile acids to keep cholesterol dissolved in the bile, resulting in gallstone formation.
8. Increased blood triglycerides. Gallstones occur more frequently in individuals with elevated blood triglyceride levels. The reason for this is unclear.

The risk for pigment gallstones

• Black pigment gallstones form whenever an increased load of bilirubin reaches the liver. This occurs when there is increased destruction of red blood cells, as in diseases such as sickle cell disease and thalassemia. Black pigment gallstones also are more common in patients with cirrhosis of the liver.
• Brown pigment gallstones form when there is stasis of bile (decreased flow), for example, when there are narrowed or obstructed bile ducts.

Gallstones are diagnosed in one of two situations.

1. When some symptoms or signs suggest the presence of gallstones and the diagnosis of gallstones is being pursued.
2. Coincidentally while a non-gallstone-related medical problem is being evaluated.

Ultrasonography is the most important means of diagnosing gallstones. Standard computerized tomography (CT or CAT scan) and magnetic resonance imaging (MRI) may occasionally demonstrate gallstones; however, they are not as useful compared to ultrasonography because they miss gallstones.

Ultrasonography

Ultrasonography is a radiological technique that uses high-frequency sound waves to produce images of the organs and structures of the body. The sound waves are emitted from a device called a transducer and are sent through the body's tissues. The sound waves are reflected by the surfaces and interiors of internal organs and structures as "echoes." These echoes return to the transducer and are transmitted onto a viewing monitor. On the monitor, the outline of organs and structures can be determined as well as their consistency, for example, liquid or solid.

Two types of ultrasonographic techniques can be used for diagnosing gallstones: transabdominal ultrasonography and endoscopic ultrasonography.

Transabdominal ultrasonography

For transabdominal ultrasonography, the transducer is placed directly on the skin of the abdomen. The sound waves travel through the skin and then into the abdominal organs. Transabdominal ultrasonography is painless, inexpensive, and without risk to the patient. In addition to identifying 97% of gallstones in the gallbladder, abdominal ultrasonography can identify many other abnormalities related to gallstones. It can identify:

• A thickened wall of the gallbladder when there are cholecystitis and inflammation has thickened the wall
• Enlarged gallbladder and bile duct due to obstruction by gallstones
• Pancreatitis
• Fluid surrounding the gallbladder (a possible sign of inflammation) sludge

Transabdominal ultrasonography also may identify diseases not related to gallstones that may be the cause of the patient's problem, for example, appendicitis. The limitations of transabdominal ultrasonography are that it can only identify gallstones larger than 4-5 millimeters in size, and it is poor at identifying gallstones in the bile ducts.

Endoscopic ultrasonography (EUS)

For endoscopic ultrasonography, a long flexible tube - the endoscope - is swallowed by the patient after he or she has been sedated with intravenous medication. The tip of the endoscope is fitted with an ultrasound transducer. The transducer is advanced into the duodenum where ultrasonographic images are obtained.

Endoscopic ultrasonography can identify gallstones and the same abnormalities as transabdominal ultrasonography; however, since the transducer is much closer to the structures of interest - the gallbladder, bile ducts, and pancreas - better images are obtained than with transabdominal ultrasonography. Thus, it is possible to visualize smaller gallstones with EUS than transabdominal ultrasonography. EUS also is better at identifying gallstones in the common bile duct.

Although endoscopic ultrasonography is in many ways better than transabdominal ultrasonography, it is expensive, not available everywhere, and carries a small risk of complications such as those associated with the use of intravenous sedation, and intestinal perforation by the endoscope. Fortunately, transabdominal ultrasonography usually gives most of the necessary information, and endoscopic ultrasonography is needed only infrequently. Endoscopic ultrasonography also is a better way than transabdominal ultrasonography to evaluate the pancreas for pancreatitis or its complications.

Magnetic resonance cholangiopancreatography (MRCP)

Magnetic resonance cholangiopancreatography or MRCP is a modification of magnetic resonance imaging (MRI) that allows the bile and pancreatic ducts to be examined.

• For MRCP, the patient is placed in a strong magnetic field that through its energy-carrying radio waves aligns (magnetizes) the protons in the molecules of water in the tissues. (Protons are parts of the atoms that make up water molecules. All tissues in the body contain water though they contain different amounts of water.)
• Energy-carrying radio waves are passed through the tissues, and the energy is absorbed by the water's protons.
• The radio waves are turned off, and the protons release the energy they had absorbed.
• The released energy is used to form an image of the tissues and organs of the body.
• The MRI separates tissues and organs based on their concentration of water. Since different tissues contain different amounts of water, MRCP is very good at providing images of organs and tissues.
• Since bile is mostly water, MRCP gives an excellent image of bile within the gallbladder and bile ducts. The pancreatic duct, which, like the bile ducts, is filled with a watery fluid, also is seen well.
• Often an intravenous injection of a dye is used to better delineate the bile and pancreatic ducts.

The procedure is called cholangitis (referring to the bile ducts) pancreatography (referring to the pancreatic duct) because it can demonstrate the bile and pancreatic ducts.

MRCP has in many instances replaced other procedures such as cholescintigraphy (HIDA scan) and endoscopic retrograde cholangiopancreatography (ERCP) for evaluating the bile ducts. It can identify gallstones in the bile ducts, obstruction of the ducts, and leaks of bile. There are no risks to the patient with MRCP except for very rare reactions to the injected dye.

Cholescintigraphy (HIDA scan)

Cholescintigraphy is a procedure done by nuclear medicine physicians. It also is referred to as a HIDA scan or a gallbladder scan.

• For a HIDA scan, a radioactive chemical is injected intravenously into a patient.
• The radioactive chemical is removed from the blood by the liver and secreted into the bile.
• The chemical then disperses everywhere that the bile goes-into the bile ducts, the gallbladder, the intestine, and anyplace else that bile goes.
• A camera that senses radioactivity (like a Geiger counter) is then placed over the patient's abdomen and a "picture" of the liver, bile ducts, and gallbladder is obtained which corresponds to where the radioactive chemical has traveled within, or outside of the bile-filled bile ducts, and gallbladder.

HIDA scans are used to identify obstruction of the bile ducts, for example, by a gallstone. They also may identify bile leaks and fistulas. There are no risks to the patient with HIDA scans.

Cholescintigraphy also is used to study the emptying of the gallbladder. Some patients with gallstones have had gallbladder inflammation due to recognized or unrecognized episodes of cholecystitis. (There also are uncommon, non-gallstone-related causes of inflammation of the gallbladder.) The inflammation can result in scarring of the gallbladder's wall and muscle, which reduces the ability of the gallbladder to contract. As a result, the gallbladder does not empty normally. During cholescintigraphy, a synthetic hormone related to cholecystokinin (the hormone the body produces and releases during a meal to cause the gallbladder to contract) can be injected intravenously to cause the gallbladder to contract and squeeze out its bile and radioactivity into the intestine. If the gallbladder does not empty the bile and radioactivity normally, it is assumed that the gallbladder is diseased due to gallstones or non-gallstone-related inflammation.

The problem with interpreting a gallbladder emptying study is that many people with normal gallbladders have abnormal emptying of the gallbladder. Therefore, it is hazardous to base a diagnosis of a diseased gallbladder on abnormal gallbladder emptying alone.

Endoscopic retrograde cholangiopancreatography (ERCP)

ERCP is a combined endoscope and X-ray procedure performed to examine the duodenum (the first portion of the small intestine), the papilla of Vater (a small nipple-like structure where the common bile and pancreatic ducts enter the duodenum), the gallbladder, and bile and pancreatic ducts.

The procedure is performed by using a long, flexible, side-viewing instrument (a duodenoscope, a type of endoscope) about the diameter of a fountain pen. The duodenoscope is flexible and can be directed and moved around the many bends of the stomach and intestine. The video-endoscope is the most common type of duodenoscope and uses a chip at the tip of the instrument to transmit video images to a TV screen.

• First, the patient is sedated with intravenous drugs.
• The duodenoscope is inserted through the mouth, to the back of the throat, down the food pipe (esophagus), through the stomach, and into the first portion of the small intestine (duodenum).
• Once the papilla of Vater is identified, a small plastic catheter (cannula) is passed through a channel in the duodenoscope into the papilla of Vater, and into the bile ducts and the pancreatic duct.
• Contrast material (dye) is injected, and x-rays are taken of the bile ducts, gallbladder, and/or the pancreatic duct.

ERCP can identify; 1) gallstones in the gallbladder (though it is not particularly good at this) and 2) blockage of the bile ducts, for example, by gallstones, and 3) bile leaks. ERCP also may identify diseases not related to gallstones that may be the cause of the patient's problem, for example, pancreatitis or pancreatic cancer.

An important advantage of ERCP is that instruments can be passed through the same channel as the cannula used to inject the dye to extract gallstones stuck in the common and hepatic ducts. This can save the patient from having an operation. ERCP has several risks associated with it, including the drugs used for sedation, perforation of the duodenum by the duodenoscope, and pancreatitis (due to damage to the pancreas). If gallstones are extracted, bleeding also may occur as a complication.

Liver and pancreatic blood tests

When the liver or pancreas becomes inflamed or their ducts become obstructed and enlarged, the cells of the liver and pancreas release some of their enzymes into the blood. The most commonly measured liver enzymes in blood are aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The most commonly-measured pancreatic enzymes in blood are amylase and lipase. Many medical conditions that affect the liver or pancreas cause these blood tests to become abnormal, so these abnormalities alone cannot be used to diagnose gallstones. Nevertheless, abnormalities of these tests suggest there is a problem with the liver, bile ducts, or pancreas, and gallstones are a common cause of such abnormal tests, particularly during sudden obstruction of the bile ducts or pancreatic ducts. Thus, abnormal liver and pancreatic blood test direct attention to the possibility that gallstones may be causing the acute problem.

Duodenal biliary drainage

Duodenal biliary drainage is a procedure that occasionally can be useful in diagnosing gallstones; however, it is not often used. As previously discussed, gallstones begin as microscopic particles of cholesterol or pigment that grow in size. It is clear that some people who develop biliary colic, cholecystitis, or pancreatitis have only these particles in their gallbladders, yet the particles are too small to obstruct the ducts. There are two potential explanations for how obstruction might occur in this situation. The first is that a small gallstone initially caused an obstruction before passing through the bile ducts into the intestine. The second is that particles passing through the bile ducts can "irritate" the ducts, causing spasm of the muscle within the walls of the ducts (which obstructs the flow of bile) or inflammation of the duct that causes the wall of the duct to swell (which also obstructs the duct).

• For duodenal drainage, a thin plastic or rubber tube with several holes at its tip is passed through a patient's anesthetized nostril, down the back of the throat, through the esophagus and stomach, and into the duodenum where the bile and pancreatic ducts enter the small intestine. This is done with the help of an x-ray (fluoroscopy).
• Once the tube is in place, a synthetic hormone related to cholecystokinin, the hormone that is normally released after a meal to cause the gallbladder, is injected intravenously. As a result, the gallbladder contracts and squeezes out its concentrated bile into the duodenum.
• The bile is sucked through the tube in the duodenum and examined for the presence of small cholesterol and pigment particles under a microscope.

The risks to the patient of duodenal drainage are minimal. (There have been no reports of reactions to the synthetic hormone.) Nevertheless, duodenal drainage is uncomfortable.

A modification of duodenal drainage involves the collection of bile through an endoscope at the time of an upper gastrointestinal endoscopy-either esophagogastroduodenoscopy (EGD) or ERCP.

Oral cholecystogram (OCG)

The oral cholecystogram or OCG is a radiologic (X-ray) procedure for diagnosing gallstones.

• The patient takes iodine-containing tablets for one or two nights in a row and then has an X-ray of the abdomen.
• The iodine is absorbed from the intestine into the blood, removed from the blood by the liver, and excreted into the bile.
• In the gallbladder, the iodine becomes concentrated along with the bile.
• On the X-ray, the iodine, which is dense and stops X-rays, fills the gallbladder and outlines the gallstones that are not dense, and allows X-rays to pass through them. The ducts cannot be seen on the x-ray because the iodine is not concentrated in the ducts.

The OCG is an excellent procedure for diagnosing gallstones; it finds 95% of them. The OCG has been replaced, however, by ultrasonography because ultrasonography is slightly better at finding gallstones and can be done immediately without waiting one or two days for the iodine to be absorbed, excreted, and concentrated.

Unlike ultrasonography, the OCG also cannot give information about the presence of non-gallstone-related diseases. As would be expected, ultrasonography sometimes finds gallstones that are missed by the OCG. Less frequently, the OCG finds gallstones that are missed by ultrasonography. For this reason, if there is a strong suspicion that gallstones are present but ultrasonography does not show them, it is reasonable to consider doing an OCG; however, EUS has mostly replaced the OCG in this situation. An OCG should not be done in individuals who are allergic to iodine.

Intravenous cholangiogram (IVC)

The intravenous cholangiogram or IVC is a radiologic (X-ray) procedure that is used primarily for looking at the larger intrahepatic and extrahepatic bile ducts. It can be used to locate gallstones within these ducts.

An iodine-containing dye is injected intravenously into the blood. The dye is removed from the blood by the liver and excreted into the bile. Unlike the iodine used in the OCG, the iodine in the IVC is concentrated sufficiently enough in the bile ducts to outline the ducts and any gallstones within them. The IVC is rarely used because it has been replaced by MRI cholangiography and endoscopic ultrasound. Moreover, occasional serious reactions to the iodine-containing dye can occur, which rarely may result in the death of the patient.

Usually, it is not difficult to diagnose gallstones. Problems arise, however, because of the high prevalence of silent gallstones and the occasional gallstone that is difficult to diagnose.

If a patient has symptoms that are typical for gallstones, for example, biliary colic, cholecystitis, or pancreatitis, and has gallstones on ultrasonography, little else usually needs to be done to demonstrate that the gallstones are causing the symptoms unless the patient has other complicating medical issues.

If symptoms are not typical for gallstones there is a possibility that the gallstones are innocent bystanders (silent), and most importantly, removing the gallbladder surgically will not resolve the patient's problem or prevent further symptoms. In addition, the real cause of the symptoms will not be pursued. In such a situation, there is a need to obtain further evidence, other than their mere presence, that the gallstones are causing the problem. Such evidence can be obtained during an acute episode or shortly thereafter.

If ultrasonography can be done during an acute episode of pain or inflammation caused by gallstones, it may be possible to demonstrate an enlarged gallbladder or bile duct caused by obstruction of the ducts by the gallstone. This is likely to require ultrasonography again after the episode has resolved in order to demonstrate that the gallbladder indeed was larger during the episode than before or after the episode. It is easier to obtain the necessary ultrasonography if the episode lasts several hours, but it is much more difficult to obtain ultrasonography rapidly enough if the episode lasts only 15 minutes.

Another approach is to test the blood for abnormal liver and pancreatic enzymes. The advantage here is that the enzymes, though not always elevated, can be elevated during an acute attack and for several hours after an episode of gallstone-related pain or inflammation, so they may be abnormal even after the episode has subsided. It is important to remember, however, that the enzymes are not specific for gallstones, and it is necessary to exclude other liver and pancreatic causes for abnormal enzymes.

Sometimes, episodes of pain or inflammation may be more or less typical of gallstones, but transabdominal ultrasonography may not demonstrate either gallstones or another cause of the episodes. In this situation, it is necessary to decide whether the suspicion is high or low for gallstones as a cause of the episodes. If suspicion is low because of lack of typical symptoms, it may be reasonable only to repeat the ultrasonography, possibly obtain an OCG, and/or test for abnormalities of liver or pancreatic enzymes. If suspicion is high because of more typical symptoms, it is reasonable to investigate even further with endoscopic ultrasonography, ERCP, and duodenal drainage. Prior to these "invasive" procedures, some physicians recommend MRCP.

Observation

Most gallstones are silent and do not need treatment.

• If silent gallstones are discovered in an individual at age 65 (or older), the chance of developing symptoms from the gallstones is only 20% (or less) assuming a life span of 75 years. In this instance, it is reasonable not to treat the individual.
• In younger individuals, no treatment also may be appropriate if the individuals have serious, life-threatening diseases, for example, serious heart disease, that is likely to shorten their life span.
• On the other hand, in healthy young individuals, treatment should be considered even for silent gallstones because the individuals' chances of developing symptoms from the gallstones over a lifetime will be higher. Once symptoms begin, treatment should be recommended since further symptoms are likely, and more serious complications can be prevented.

Cholecystectomy

Cholecystectomy (removal of the gallbladder surgically) is the standard treatment for gallstones in the gallbladder. Surgery may be done through a large abdominal incision, laparoscopically, or robotically through small punctures in the abdominal wall. Laparoscopic surgery results in less pain and a faster recovery. Robot-assisted laparoscopic surgery has 3D visualization. Cholecystectomy has a low rate of complications, but serious complications such as damage to the bile ducts and leakage of bile occasionally occur. There also is risk associated with the general anesthesia that is necessary for either type of surgery. Problems following removal of the gallbladder are few. Digestion of food is not affected, and no change in diet is necessary. Nevertheless, chronic diarrhea occurs in approximately 10% of patients.

Sphincterotomy and extraction of gallstones

Sometimes a gallstone may be stuck in the hepatic or common bile ducts. In such situations, there usually are gallstones in the gallbladder as well, and cholecystectomy is necessary. It may be possible to remove the gallstone stuck in the duct at the time of surgery, but this may not always be possible. An alternative means for removing gallstones in the duct before or after cholecystectomy is with sphincterotomy followed by extraction of the gallstone.

Sphincterotomy involves cutting the muscle of the common bile duct (sphincter of Oddi) at the junction of the common bile duct and the duodenum in order to allow easier access to the common bile duct. The cutting is done with an electrosurgical instrument passed through the same type of endoscope that is used for ERCP. After the sphincter is cut, instruments may be passed through the endoscope and into the hepatic and common bile ducts to grab and pull out the gallstone or to crush the gallstone. It also is possible to pass a lithotripsy instrument that uses high-frequency sound waves to break up the gallstone. Complications of sphincterotomy and extraction of gallstones include risks associated with general anesthesia, perforation of the bile ducts or duodenum, bleeding, and pancreatitis.

Oral dissolution therapy

It is possible to dissolve some cholesterol gallstones with medication taken orally. The medication is a naturally occurring bile acid called ursodeoxycholic acid or ursodiol (Actigall, Urso). Bile acids are one of the detergents that the liver secretes into bile to dissolve cholesterol. Although one might expect therapy with ursodiol to work by increasing the number of bile acids in bile and thereby cause the cholesterol in gallstones to dissolve, the mechanism of ursodiol's action actually is different. Ursodiol reduces the amount of cholesterol secreted in bile. The bile then has less cholesterol and becomes capable of dissolving the cholesterol in the gallstones.

There are important limitations to the use of ursodiol:

• It is only effective for cholesterol gallstones and not pigment gallstones.
• It works only for small gallstones, less than 1-1.5 cm in diameter.
• It takes one to two years for the gallstones to dissolve, and many of the gallstones reform following cessation of treatment.

Due to these limitations, ursodiol generally is used only in individuals with smaller gallstones that are likely to have a very high cholesterol content and who are at high risk for surgery because of ill health. It also is reasonable to use ursodiol in individuals whose gallstones were perhaps formed because of a transient event, for example, the rapid loss of weight, since the gallstones would not be expected to recur following successful dissolution. Another use of ursodiol is to prevent the formation of gallstones in patients who will lose weight rapidly.

Extracorporeal shock-wave lithotripsy

Extracorporeal shock-wave lithotripsy (ESWL) is an infrequently used method for treating gallstones, particularly those lodged in bile ducts. ESWL generators produce shock waves outside of the body that is then focused on the gallstone. The shock waves shatter the gallstone, and the resulting pieces of the gallstone either drain into the intestine on their own or are extracted endoscopically. Shock waves also can be used to break up gallstones via special catheters passed through an endoscope at the time of ERCP.

There are no natural or home remedies to treat gallstones.

Biliary colic is the most common symptom of gallstones, but, fortunately, it is usually a self-limited symptom. There are, however, more serious complications of gallstones.

Cholecystitis

Cholecystitis means inflammation of the gallbladder. Like biliary colic, it too is caused by sudden obstruction of the ducts, usually the cystic duct by a gallstone. In fact, cholecystitis may begin with an episode of biliary colic. Obstruction of the cystic duct causes the wall of the gallbladder to begin secreting fluid, but for unclear reasons, inflammation sets in. At first, the inflammation is sterile, that is, there is no infection with bacteria; however, over time the bile and gallbladder become infected with bacteria that travel through the bile ducts from the intestine.

With cholecystitis, there is a constant pain in the right upper abdomen. The inflammation extends through the wall of the gallbladder, and the right upper abdomen becomes particularly tender when it is pressed or even tapped. Unlike with biliary colic, however, it is painful to move around. Individuals with cholecystitis usually lie still. There is fever, and the white blood cell count is elevated, both signs of inflammation. Cholecystitis usually is treated with antibiotics, and most episodes will resolve over several days. Even without antibiotics, cholecystitis often resolves. As with biliary colic, movement of the gallstone out of the cystic duct and back into the gallbladder relieves the obstruction and allows the inflammation to resolve.

Cholangitis

Cholangitis is a condition in which bile in the common, hepatic, and intrahepatic ducts becomes infected. Like cholecystitis, the infection spreads through the ducts from the intestine after the ducts become obstructed by a gallstone. Patients with cholangitis are very sick with high fever and elevated white blood cell counts. Cholangitis may result in an abscess within the liver or sepsis. (See the discussion of sepsis that follows.)

Gangrene

Gangrene of the gallbladder is a condition in which the inflammation of cholecystitis cuts off the supply of blood to the gallbladder. Without blood, the tissues forming the wall of the gallbladder die, and this makes the wall very weak. The weakness combined with infection often leads to rupture of the gallbladder. The infection then may spread throughout the abdomen, though often the rupture is confined to a small area around the gallbladder (a confined perforation).

Jaundice

Jaundice is a condition in which bilirubin accumulates in the body. Bilirubin is brownish-black in color but is yellow when it is not too concentrated. A build-up of bilirubin in the body turns the skin and whites of the eye (sclera) yellow. Jaundice occurs when there is prolonged obstruction of the bile ducts. The obstruction may be due to gallstones, but it also may be due to many other causes, for example, tumors of the bile ducts or surrounding tissues. (Other causes of jaundice are rapid destruction of red blood cells that overwhelms the ability of the liver to remove bilirubin from the blood or a damaged liver that cannot remove bilirubin from the blood normally.) Jaundice, by itself, generally does not cause problems.

Pancreatitis

Pancreatitis means inflammation of the pancreas. The two most common causes of pancreatitis are alcoholism and gallstones. The pancreas surrounds the common bile duct as it enters the intestine. The pancreatic duct that drains the digestive juices from the pancreas joins the common bile duct just before it empties into the intestine. If a gallstone obstructs the common bile duct just after the pancreatic duct joins it, the flow of pancreatic juice from the pancreas is blocked. This results in inflammation within the pancreas. Pancreatitis due to gallstones usually is mild, but it may cause serious illness and even death. Fortunately, severe pancreatitis due to gallstones is rare.

Sepsis

Sepsis is a condition in which bacteria from any source within the body, including the gallbladder or bile ducts, enter into the bloodstream and spread throughout the body. Although the bacteria usually remain within the blood, they also may spread to distant tissues and lead to the formation of abscesses (localized areas of infection with formation of pus). Sepsis is a feared complication of any infection. The signs of sepsis include high fever, high white blood cell count, and, less frequently, rigors (shaking chills) or a drop in blood pressure.

Fistula

A fistula is an abnormal tract through which fluid can flow between two hollow organs or between an abscess and a hollow organ or skin. Gallstones cause fistulas when the hard gallstone erodes through the soft wall of the gallbladder or bile ducts. Most commonly, the gallstone erodes into the small intestine, stomach, or common bile duct. This can leave a tract that allows bile to flow from the gallbladder to the small intestine, stomach, or the common bile duct. If the fistula enters the distal part of the small intestine, the concentrated bile can lead to problems such as diarrhea. Rarely, the gallstone erodes into the abdominal cavity. The bile then leaks into the abdominal cavity and causes inflammation of the lining of the abdomen (peritoneum), a condition called bile peritonitis.

Ileus

Ileus is a condition in which there is an obstruction to the flow of food, gas, and liquid within the intestine. It may be due to a mechanical obstruction, for example, a tumor within the intestine, or a functional obstruction, for example, inflammation of the intestine or surrounding tissues that prevents the muscles of the intestine from working normally and propelling intestinal contents. If a large gallstone erodes through the wall of the gallbladder and into the stomach or small intestine, it will be propelled through the small intestine. The narrowest part of the small intestine is the ileocecal valve, which is located at the site where the small intestine joins the colon. If the gallstone is too large to pass through the valve, it can obstruct the small intestine and cause an ileus. Gallstones also may cause ileus if there are other abnormal narrowings in the intestine such as a tumor or scarring.

Cancer

Cancer of the gallbladder usually is associated with gallstones, but it is not clear which comes first, that is, whether the gallstones precede cancer and, therefore, could potentially be the cause of cancer or the gallstones form because cancer is present. Cancer of the gallbladder arises in less than 1% of individuals with gallstones. Therefore, concern about the future development of cancer is by itself not a good reason for removing the gallbladder when gallstones are present.

Sludge is a common term that is applied to an abnormality of bile that is seen with ultrasonography of the gallbladder. Specifically, the bile within the gallbladder is seen to be of two different densities with the denser bile on the bottom. The bile is denser because it contains microscopic particles, usually cholesterol or pigment, embedded in mucus. (The mucus is secreted by the gallbladder.) Over time, sludge may remain in the gallbladder, it may disappear and not return, or it may come and go. As discussed previously, these particles may be precursors of gallstones, and they occur often in some situations in which gallstones frequently appear, for example, rapid weight loss, pregnancy, and prolonged fasting.

Nevertheless, it appears that sludge goes on to become gallstones in only a minority of individuals. Just to make matters more difficult, it is not clear how often - if at all - sludge alone causes problems. Sludge has been blamed for many of the same symptoms as gallstones-biliary colic, cholecystitis, and pancreatitis, but often these symptoms and complications are caused by very small gallstones that are missed by ultrasonography. Thus, there is some uncertainty about the importance of sludge.

It is clear, however, that sludge is not the equivalent of gallstones. The practical implication of this uncertainty is that unless an individual's symptoms are typical of gallstones, sludge should not be considered as a possible cause of the symptoms.

Ideally, it would be better if gallstones could be prevented rather than treated. Prevention of cholesterol gallstones is feasible since ursodiol, the bile acid medication that dissolves some cholesterol gallstones, also prevents them from forming. The difficulty is to identify individuals who are at a high risk for developing cholesterol gallstones over a relatively short period of time so that the duration of preventive treatment can be limited. One such group is obese individuals losing weight rapidly with very low calorie diets or with surgery. The risk of gallstones in this group is as high as 40% to 60%. In fact, ursodiol has been shown in several studies to be very effective at preventing gallstones in these individuals. It is important to stress that no dietary changes have been shown to treat or prevent gallstones.

Gallstones usually are diagnosed by a gastroenterologist, a medical subspecialist who deals with diseases of the intestine, liver, pancreas, and gallbladder. General surgeons also may be involved in the diagnosis of gallstones but usually are the doctors who treat gallstones because the common treatment is surgical removal of the gallbladder.

It is clear that genetic factors are important in determining who develops gallstones. Current scientific studies are directed at uncovering the specific genes that are responsible for gallstones. To date, 8-10 genes have been identified as being associated with cholesterol gallstones, at least in animals that develop cholesterol gallstones. Not surprisingly, the products of many of these genes control the production and secretion (by the liver) of cholesterol, bile acids, and lecithin. The long-term goal is to be able to identify individuals who are genetically at very high risk for cholesterol gallstones and to offer them preventive treatment. An understanding of the exact mechanism(s) of gallstone formation also may result in new therapies for treatment and prevention.

Surgery for gallstones has undergone a major transition from requiring large abdominal incisions to requiring only tiny incisions for laparoscopic instruments (laparoscopic cholecystectomy). It is possible that there will be another transition. Surgeons are experimenting with a technique called natural orifice transluminal endoscopic surgery (NOTES). NOTES is a new technique for accomplishing standard intra-abdominal surgery, but access to the abdomen is through a natural orifice - the mouth, anus, or vagina.

For NOTES, a flexible endoscopic instrument is similar to the flexible endoscopes presently being used widely is introduced through the chosen orifice, through an incision somewhere inside the orifice (for example, the stomach), and into the abdominal cavity. Thus, the only incision is within the body and not visible on the body's surface. There are potential advantages to this type of surgery, but it is in the early stages of development, and it is unclear what the future role of NOTES will be in gallbladder surgery. Nevertheless, several series of patients have already been described who have had their gallbladders removed via NOTES primarily through the vagina.