Esteban Mezey
John W. Harmon
Diseases of the biliary tract are commonly encountered in ambulatory practice. Many patients are discovered to have asymptomatic gallstones during the course of evaluation of another condition; others are found to have symptomatic chronic cholecystitis. Less commonly, patients present with an acute illness caused by acute cholecystitis or common bile duct obstruction. This chapter describes the cause, diagnosis, and treatment of these various conditions.
Cholelithiasis
Epidemiology
Approximately 10% of the U.S. population has gallstones. In their lifetime, only 50% will ever be symptomatic, with 80% of them having chronic symptoms and 20% presenting with an acute illness. About 500,000 cholecystectomies are performed each year in the United States.
Ninety percent of gallstones found in patients in the United States are cholesterol gallstones; 10% are pigment (bilirubinate) stones. The prevalence of gallstones is greater in women than in men and increases with age. In the United States, 10% to 15% of men and 20% to 40% of women older than age 60 years are affected (1). The prevalence of cholesterol gallstones is particularly high in the Native Americans of the southwestern United States; for example, 70% of Pima women older than age 25 years have cholelithiasis (2).
Gallstone Formation
Bile is produced in the liver and excreted into the duodenum and contains bile acids (primarily cholic, deoxycholic, and chenodeoxycholic acid), phospholipids (primarily lecithin), and cholesterol. The solubility of cholesterol depends on its incorporation with bile and phospholipids into a micelle. In the intestinal tract, bile salts are necessary for the absorption of dietary fats; they solubilize fatty acids and monoglycerides into micellar solutions. The fatty acids are absorbed in the jejunum, whereas the bile salts are absorbed in the ileum and enter the enterohepatic circulation.
Three major types of gallstones form in human bile: cholesterol stones (more than 70% cholesterol), mixed stones (50% to 70% cholesterol), and pigment stones (12% cholesterol). These stones probably develop in three stages: first, the formation of a supersaturated bile; second, the crystallization or initiation of stone formation; and third, the growth of the stone to a certain detectable size before crystals in the bile are expelled into the intestine. It is likely, but not clearly established, that one of these stages is more important in the formation of certain types of stones than in others.
Cholesterol Stones
The hypersecretion of biliary cholesterol appears to be the real culprit in the pathogenesis of cholesterol stones, but this might not be true in all patients. Several mechanisms of increased cholesterol secretion have been identified (1). Cholesterol crystals form when the amount of cholesterol in bile exceeds the solubilizing properties of bile salts and phospholipid (supersaturated bile). The cholesterol crystals are caught in a film of mucin gel that lines the
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gallbladder and provides a nucleus for the formation of gallstones. Growth of these stones occurs, especially in a dyskinetic gallbladder, one in which contraction is impaired, as in diabetes mellitus and pregnancy. The mucin gel itself might decrease gallbladder motility and emptying.
Pigment Stones
Formation of pigment stones is probably initiated by supersaturation of unconjugated bilirubin in the gallbladder and common bile duct. Unconjugated bilirubin, like cholesterol, is insoluble in water. An increased concentration of unconjugated bilirubin in bile results either from its formation from conjugated bilirubin in the biliary tree through the action of a glucuronidase (perhaps of bacterial origin, in patients with infected bile; see Signs and Symptoms section) or from increased production of unconjugated bilirubin by the liver (e.g., in patients with hemolytic anemia). A diseased gallbladder is probably not a factor in the formation of pigment stones.
Risk Factors
Because most patients with cholelithiasis are asymptomatic, it is difficult to evaluate risk factors precisely. Table 96.1 lists known risk factors for the development of cholesterol and pigment stones (3).
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TABLE 96.1 Risk Factors for Gallstones |
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Cholesterol Stones
The demography of cholesterol stones probably reflects both genetic predisposition and nongenetic ethnic characteristics. For example, it is known that obese people and nonobese people who eat a high-calorie diet secrete more cholesterol into their bile than the average person. Therefore, populations in whom obesity is common (e.g., the Native Americans of the American southwest) or who consume high-calorie diets (occidental societies in general) are more susceptible to cholelithiasis.
The reasons for the increasing incidence of gallstones in middle-aged and elderly people are unknown but may be related to the time that elapses between formation of supersaturated bile and formation of stones and between formation of stones and recognition of them. The enhancement by estrogens of the secretion of cholesterol in bile is reflected in the higher prevalence of gallstones in women (between puberty and menopause) than in men (see above) and in women who take estrogenic preparations compared with women who do not (seeChapters 100 and 106).
Finally, there are a number of ways by which the concentration of bile acids in bile is reduced, favoring the formation of gallstones: Drugs used to treat hyperlipidemia, such as clofibrate, cholestyramine, gemfibrozil, and colestipol (see Chapter 82), decrease bile acid secretion, and certain disorders of the gastrointestinal (GI) tract (ileal resection, Crohn disease of the ileum) reduce bile acid resorption.
Pigment Stones
The demography of pigment stones is entirely different from that of cholesterol stones. The propensity of Asian people to develop pigment stones is not entirely understood, but it may be attributable to the higher prevalence of bacterial infection of the bile (usually Escherichia coli infections) and of Ascaris infestation in the Orient compared with the Occident. In the United States, patients with pigment gallstones do not usually have infected or infested bile. The recognized risk factors in the United States are hemolysis and alcoholic cirrhosis. Like cholesterol stones, pigment stones are more common with advancing age, but endogenous and exogenous estrogens and obesity have no influence on their development.
Natural History
Many attempts have been made to study the natural history of gallstones among the 2 to 3 million people in the United States known to have them. Of these people, 50% are asymptomatic, having had gallstones discovered incidentally on abdominal radiography (10% to 15% are radiopaque) or another imaging study or during celiotomy for treatment of another condition. The other 50% are
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symptomatic and gallstones are discovered during evaluation of the typical or atypical abdominal pain of acute or chronic cholecystitis.
Approximately 18% of people with silent gallstones develop symptoms in 15 to 20 years, and 3% develop complications of biliary tract disease, namely acute cholecystitis, pancreatitis, or obstructive jaundice (4). The risk of developing complications is unrelated to the severity of symptoms but does increase with the length of time symptoms have been present. Most complications occur only among symptomatic patients. However, 20% of the time acute cholecystitis is the first indication of cholelithiasis. Complications, if they occur, are usually experienced within 5 years of the discovery of gallstones.
Causes of death related to cholelithiasis among patients not having cholecystectomy are acute cholecystitis, cholangitis with liver abscess, necrotizing pancreatitis, gallbladder carcinoma, and gallstone ileus with mechanical small bowel obstruction. In Lund's study of the natural history of cholelithiasis, 2.7% of the deaths among patients not operated on were attributed to gallbladder disease (5).
Asymptomatic Patients
It cannot be predicted on the basis of the size or number of stones or the sex or age of the patient which asymptomatic patients are likely to become symptomatic. Whether asymptomatic patients should undergo elective cholecystectomy, therefore, depends largely on the bias of the primary clinician and the consulting surgeon. Approximately 18% of patients become symptomatic some time at a point in their lives when operation is more dangerous because of age, intercurrent illness, or the presence of acute cholecystitis. The risk of complications of cholelithiasis, other than acute cholecystitis, is negligible in the asymptomatic patient. Carcinoma of the gallbladder is more common among people with gallstones and the risk—0.3% to 1% over a lifetime—is approximately the same as the historic operative mortality from cholecystectomy. However, recent technologic changes have decreased the operative risk considerably. If the gallbladder is calcified, the risk of cancer is nearly 50%, however, and cholecystectomy should be performed. Likewise, prophylactic cholecystectomy is recommended for Native Americans with cholelithiasis, because they have a 3% to 5% risk of developing gallbladder cancer (6). Prophylactic cholecystectomy has also been recommended for children with gallstones, in whom symptoms almost always develop (7), and in patients with sickle cell anemia and cholelithiasis because the symptoms of either condition can easily be confused with the other. Otherwise, the current consensus at this point is not to recommend elective cholecystectomy in the asymptomatic patient. The legitimacy of this same approach in the diabetic patient has been endorsed (8). This recommendation is unchanged even with the emergence of laparoscopic cholecystectomy and its attendant lower morbidity and shortened convalescence (see below).
Cholecystitis
The hallmark of cholecystitis is abdominal pain (9), often epigastric at onset, but localizing within a few hours to the right upper quadrant. The pain is characteristically, but not always, severe and unremitting, with only slight variations in intensity. Use of the term biliary colic, therefore, is not precise because colic is defined as pain that waxes and wanes. Some patients describe the pain as heavy and aching and others as knife-like. Occasionally, it radiates into the right side of the back or, less often, into other parts of the abdomen. The pain, often accompanied by slight nausea, usually begins abruptly, within 1 to 3 hours of eating a meal. (The historical association of the pain with fatty food intolerance is unfounded [10].) Patients may also complain of being awakened in the middle of the night. A typical attack subsides spontaneously within 2 to 3 hours. The frequency of such attacks is extremely variable, from every day to only once or twice a year.
A patient who presents with this history is very likely to have gallstones. However, the degree of inflammation of the gallbladder cannot be determined from the history. There may be gallstones without any inflammation at all, there may be acute inflammation, or there may be chronic inflammation with fibrosis. However, an attack lasting more than 6 hours generally heralds the onset of acute cholecystitis (acute inflammation). The severity of the symptoms and the presence or absence of signs of inflammation or biliary obstruction determine the clinician's response (see Cholecystostomy section).
Acute Cholecystitis
Pathophysiology
More than 90% of the time, acute cholecystitis is caused by a gallstone that obstructs the cystic duct. Acute acalculous cholecystitis occurs primarily in patients who have sustained major trauma, including major operations. Inflammation of the gallbladder in early acute cholecystitis is probably caused by irritation by concentrated static bile. As the process progresses, the bile often becomes infected; bile cultures are positive in only 20% to 30% of patients during the first few days of an attack, but by 7 to 10 days, almost 80% of biliary cultures are positive. In certain patients, such as diabetics and patients with acalculous cholecystitis, mural ischemia might also play a role. The difference between the presentation of acute and chronic cholecystitis (see below) is probably caused by the length of time the cystic duct has been totally obstructed and by the intensity of the inflammation.
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Signs and Symptoms
The pain of classic acute cholecystitis is severe and persistent. It is usually accompanied by nausea and fever (99°F to 102°F [37°C to 39°C]) and, less often, by vomiting. Unless treated, the symptoms are likely to persist for up to a week.
The severity and persistence of the pain usually cause the patient to see his or her caregiver (see Chapter 45 for a general discussion of abdominal pain). On examination, the patient is restless. There is considerable right upper quadrant abdominal tenderness, associated with involuntary guarding of the abdominal wall. This guarding, indicative of early peritoneal inflammation, is particularly important to recognize. It is not a feature of less acute disease (see Chronic Cholecystitis section). Murphy sign, the sudden involuntary arrest of inspiration (because of pain) when the examiner palpates the right upper quadrant during inspiration, is caused by the abutment of the inflamed gallbladder against the examiner's fingers as it moves downward with expansion of the chest cavity. This sign is more often elicited after several days of inflammation. In one third of patients, the gallbladder is palpable during an attack of acute cholecystitis if the right upper quadrant is probed very gently. Occasionally, patients are mildly jaundiced.
Laboratory Tests
Leukocytosis (12,000 to 15,000 white blood cells per cubic millimeter) caused by a neutrophilic granulocytosis is common. Serum amylase activity may be increased in the absence of other evidence of acute pancreatitis. Often, the activity of serum aminotransferases (aspartate aminotransferase and alanine aminotransferase) is increased as well. Twenty percent of patients have mild hyperbilirubinemia (less than 4 mL/100 mL).
Biliary scintigraphy is the test of choice in the diagnosis of acute cholecystitis. The imaging compounds are 99mTechnicium (99mTc)-labeled derivatives of iminodiacetic acid (technetium hepatoiminodiacetic acid [TcHIDA], paraisopropyliminodiacetic acid [PIPIDA], or diisopropyl iminodiacetic acid [DISIDA]), which are concentrated in bile. The study requires injection of isotope intravenously and evaluation of uptake of the isotope by the gallbladder. If the cystic duct is obstructed, because of acute inflammation or because of a stone, uptake does not occur. The test takes 1 to 4 hours to complete. A positive study shows isotope in the biliary tree and in the duodenum but not in the gallbladder. A negative study shows isotope in the gallbladder as well. If isotope is not excreted, the test is uninterpretable, but if it is excreted, the sensitivity of the test is extremely high (essentially 100%). Specificity is also high (95%), but false positive results may occur in patients with chronic cholecystitis or acute biliary obstruction caused by pancreatitis.
Ultrasonography (US) may also be used to diagnose acute cholecystitis in a patient with characteristic symptoms. If there are stones in the gallbladder, thickening or edema of the wall, or an “ultrasonic Murphy sign” (produced by the pressure of the transducer on the inflamed gallbladder), the positive and negative predictive value of the test is greater than 92% (11).
Differential Diagnosis
The differential diagnosis must include disorders that might cause severe right upper quadrant abdominal pain and, usually, leukocytosis and slightly abnormal hepaticT tests: acute pancreatitis, appendicitis, hepatitis, hepatic abscess, a perforated or penetrated peptic ulcer, acute pyelonephritis, myocardial infarction (MI), and right lower lobe pneumonia or pleuritis. Because of the severity of the illness, these distinctions should be made in the hospital.
Treatment
The patient suspected of having acute cholecystitis should be hospitalized for observation, hydration, and further diagnostic procedures (see below and Chapter 45 for a discussion of these procedures as they pertain to ambulatory patients). If the pain is intolerable, the caregiver can administer a narcotic parenterally while arranging admission. The patient should be told that in the hospital intravenous rather than oral feeding will be given, that if there is vomiting a nasogastric tube will be passed, and that antibiotics will be administered. Because 30% to 40% of patients develop gangrenous or perforated gallbladders if cholecystectomy is delayed, urgent operation is generally indicated once the diagnosis is made, especially in diabetics and in the elderly (12,13), among whom rapid development of complications is more likely. A randomized prospective study that compared early and delayed cholecystectomy for acute cholecystitis concluded that the duration of hospitalization and the duration of disability were significantly reduced by early operation (14). The presence of emphysematous cholecystitis caused by gas-forming bacterial infection dictates emergency operation (air bubbles in the right upper quadrant on a plain film of the abdomen indicate the diagnosis). Laparoscopic cholecystectomy is ordinarily the operative procedure of choice (15). A discussion of surgery of the biliary tract and of the results and complications of operations is provided below.
Chronic Cholecystitis
Pathophysiology
Symptomatic chronic cholecystitis is associated with gallstones more than 95% of the time; the remaining cases are
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caused by other diseases of the gallbladder, such as cholesterolosis (the appearance of macrophages laden with cholesterol crystals in the wall of the gallbladder, often without stones). Recurring attacks of mild acute cholecystitis cause eventual fibrosis, so the gallbladder empties poorly. The symptoms of chronic disease, like those of acute cholecystitis, are caused by obstruction by a gallstone of the cystic duct. In chronic recurrent cholecystitis, obstruction of the cystic duct is of short duration (probably no more than a few hours) compared with the length of time of obstruction in acute cholecystitis, so inflammation is less intense. Chronicity of symptoms may also be related to gallbladder dyskinesia secondary to mural fibrosis.
Signs and Symptoms
Many patients who complain of biliary pain for the first time probably already have chronic gallbladder inflammation. The character and location of the pain are identical to those of acute cholecystitis. Pain is variably associated with nausea and, occasionally, vomiting. Unlike classic acute cholecystitis, fever is unusual with chronic disease. Typically, pain occurs after eating, begins 1 to 6 hours after a meal (see above), and lasts for 2 to 3 hours. Nonspecific symptoms—postprandial pain, bloating, belching, flatulence, so-called fatty food intolerance—thought by many to suggest gallbladder disease, are extremely common in the general population and therefore are not helpful diagnostically.
The patient with chronic cholecystitis usually seeks care less urgently than does the patient with acute cholecystitis. On examination during the attack, although there is tenderness to deep palpation in the right upper quadrant of the abdomen, there is no muscle guarding, as there is in patients with acute inflammation. Murphy sign (see above) is absent, the gallbladder is rarely palpable, and jaundice usually is not present. Between attacks, there is no abdominal tenderness.
Laboratory Tests
The white blood count, serum amylase, serum aminotransferases, and serum bilirubin are usually normal. Unlike patients with acute cholecystitis, patients with symptoms of chronic cholecystitis can be evaluated further in an ambulatory setting, but some are hospitalized early in an attack because of an inability to distinguish it from an episode of acute cholecystitis. If a TcHIDA scan is obtained to help in making that distinction, it may be positive, even in patients with chronic cholecystitis, because of transient obstruction of the cystic duct.
Abdominal Ultrasound
Ultrasound has replaced oral cholecystography (at approximately the same cost) as the principal test for the detection of gallstones. The advantages of ultrasound are that it exposes the patient to no radiation, it is much quicker (5 to 10 minutes), and it has no side effects. It is not influenced by associated GI or hepatic disease. The detection rate for gallstones 3 mm or greater in diameter is 89% to 96% by ultrasound with 93% to 97% specificity (3% to 7% false-positive) (16).
Oral Cholecystogram
The oral cholecystogram documents whether the gallbladder is functioning and whether radiolucent stones are present. Currently, it is obtained only if ultrasound is equivocal. Approximately 75% of gallbladders are visible on the first dose, and another 15% become visible on the second dose. The oral cholecystogram is reliable only if the Telepaque is ingested at the proper time, retained in the GI tract, absorbed from the small bowel, transported to the liver, esterified to glucuronide, and excreted by the liver into the bile. Therefore, GI or hepatic disease may cause a false-positive study. However, the specificity of the test is high (4% false positive) if radiolucent stones are present in an opacified gallbladder or if the gallbladder fails to concentrate contrast material after the second Telepaque dose. The sensitivity of the test is lower (10% false-negative), one of the reasons it has been replaced by ultrasonography.
Computed Tomography
Computed tomography (CT) accurately identifies gallstones 80% of the time. Currently, it has no advantages over (and costs about twice as much as) oral cholecystogram and ultrasonography in the diagnosis of gallbladder disease. However, CT might be useful occasionally if both the oral cholecystogram and ultrasound are equivocal.
Treatment
The treatment of choice for symptomatic chronic cholecystitis is elective cholecystectomy in patients who can tolerate an operation (seeCholecystostomy section). Medical therapies for cholelithiasis such as gallstone dissolution with ursodeoxycholic acid (Actigall) or gallstone lithotripsy are no longer used because of low effectiveness and high recurrence rates. These medical therapies became obsolete with the advent of laparoscopic cholecystectomy. Risks of not treating patients with chronic cholecystitis include gangrene and perforation of the gallbladder, choledocholithiasis (see Choledocholithiasis section), pancreatitis, and, rarely, gallstone ileus (the obstruction of the small bowel by a large gallstone passed through an acute fistula that has formed between the gallbladder and the duodenum).
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Symptomatic Patients Who Have No Detectable Gallstones
Adenomyomatosis of the Gallbladder
Adenomyomatosis of the gallbladder is often asymptomatic, but some patients have symptoms indistinguishable from those with chronic cholecystitis (18). The disease is caused by thickening of the gallbladder wall because of hyperplasia of the epithelium with the formation of glands and diverticula through the muscular wall. The diagnosis is often suspected during ultrasonography or cholecystography, but many cases are revealed by the pathologist after removal of the gallbladder. Adenomyomatosis is found in approximately 20% of patients who undergo cholecystectomy for biliary symptoms. It has been considered not to predispose to gallbladder cancer, but a report of a large number of cases from Japan shows a higher prevalence of gallbladder cancer in segmental adenomyomatosis, which is characterized by a concentric narrowing dividing the gallbladder into two segments (18). Cholecystectomy relieves the symptoms in most patients with symptomatic adenomyomatosis.
Carcinoma of the Gallbladder
Carcinoma of the gallbladder is often asymptomatic, but can present with abdominal pain and, when advanced, with jaundice. It is the most common tumor of the biliary tract with an incidence of approximately 1 in 10,000. It is more common in women than in men. Risk factors for carcinoma of the gallbladder are cholelithiasis, calcification of the gallbladder wall (porcelain gallbladder), and gallbladder polyps (19).
Endoscopic ultrasound (EUS) with fine-needle aspiration (FNA) is a new technique that has greatly improved the ability to diagnose carcinoma of the gallbladder. It facilitates cytological diagnosis by FNA of cholangiocarcinoma and adenocarcinoma of the gallbladder and allows differentiation of these tumors from gallbladder polyps (17). Furthermore EUS can define the extent of a tumor and the involvement of regional lymph nodes providing assistance in determining tumor resectability. The patient's experience is essentially the same as it is with endoscopy alone and the complication rate is low (17).
Surgical resection remains the only potential cure for gall bladder cancer, but unfortunately most tumors, about 90%, are not resectable at the time of diagnosis.
Biliary Dyskinesia
Some patients with symptoms suggestive of gallstones have a normal abdominal sonogram, a normal oral cholecystogram, and a normal abdominal CT. These patients may have biliary dyskinesia, a term used to denote abnormally decreased emptying of the gallbladder. The diagnosis is best made by cholecystokinin (Kinevac)-stimulated cholecystography with a TcHIDA. Often, the patient's pain is reproduced after the Kinevac injection (it stimulates gallbladder contraction), and abnormally decreased emptying of the gallbladder can be documented as a markedly decreased ejection fraction (percentage of the isotope excreted) of less than 30% compared with a group of normal subjects. Such patients, if severely symptomatic, should be offered elective cholecystectomy, after which symptoms usually abate. At operation, many of these patients prove to have stones too small to identify by ultrasonography or they have biliary sludge.
Biliary Sludge
In some symptomatic patients who have no gallstones detectable by the standard techniques, the gallbladder reflects, on US, echoes now recognized to be characteristic of biliary sludge. Of note is that EUS is more sensitive in the detection of biliary sludge than is abdominal ultrasound (20). Hence EUS is indicated in patients with symptoms of biliary-type pain who had a negative abdominal ultrasound. In some patients biliary sludge is a term applied to excessively viscous bile that contains cholesterol crystals, calcium bilirubinate granules, and mucin. In such patients duodenal drainage, ordinarily done by a consulting gastroenterologist, may prove useful in identifying the cholesterol crystals or the bilirubinate granules.
Patient Experience
The test is performed by having the patient swallow a plastic double-lumen tube, weighted at the end by a mercury-filled bag. There are holes in the tube above the bag. When the bag has passed into the second portion of the duodenum (documented by fluoroscopy), magnesium sulfate is injected into one lumen of the tube to stimulate contraction of the gallbladder. Duodenal contents are then aspirated and the sediment is separated by centrifugation and examined under a microscope. The patient's experience during this procedure is similar to that of patients undergoing upper endoscopy (see Chapter 45).
Biliary sludge may be a precursor of gallstones and of pancreatitis (21), but in a given patient the course is entirely unpredictable. Nevertheless, as with biliary dyskinesia, severely symptomatic patients with biliary sludge should be offered elective cholecystectomy.
Choledocholithiasis
Epidemiology
Common duct stones occur in approximately 15% of patients with chronic cholecystitis, either before or after
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cholecystectomy. The incidence increases with age and the length of time symptoms of gallbladder disease have been present. There are three categories of common duct stones: concomitant gallbladder stones and common duct stones, retained stones found in the common duct soon after cholecystectomy or common duct exploration, and common duct stones identified long after cholecystectomy or common duct exploration. The latter group are thought to develop in the common bile duct, and have a different consistency from stones that form in the gallbladder. They are called “earth stones” because they are soft, and not rocky hard as gallbladder stones usually are. The incidence of common duct stones decreases exponentially in the first year after cholecystectomy only to rise again, reaching a peak at 3 years. In one study, 26% of symptomatic common duct stones occurred 10 or more years after cholecystectomy (22). Also, patients with congenital agenesis of the gallbladder have a 20% incidence of common duct stones. These observations support the concept that common duct stones originate in the gallbladder or in the intrahepatic or common bile ducts.
Signs and Symptoms
Approximately 6% of patients with common duct stones are asymptomatic. More typically, patients develop severe colicky right upper quadrant pain, often associated with jaundice, mild fever, and nausea and vomiting. The pain usually begins abruptly and lasts up to an hour. If nothing is done, attacks recur at variable periods. Eventually cholangitis develops, manifested by persistent malaise and anorexia and intermittent fever, chills, and jaundice, associated with persistently high serum alkaline phosphatase activity. Suppurative ascending cholangitis characterized by right upper quadrant pain, high fever, shaking chills, and jaundice (Charcot triad) is life threatening and constitutes an emergency.
Rarely, painless jaundice is the only presenting complaint of a patient with choledocholithiasis. In such a circumstance the diagnostic studies should be the same ones performed on the patient with more typical signs and symptoms.
On physical examination, if the patient is asymptomatic, no abnormal signs are elicited. If the patient is symptomatic, right upper quadrant abdominal tenderness and muscle guarding are usually present, similar to the findings in patients with acute cholecystitis. The patient is usually mildly to moderately jaundiced.
Laboratory Tests
Because of the acute onset of symptoms and the severity of pain in patients with choledocholithiasis, laboratory studies in the ambulatory setting are usually not appropriate. If such studies are done, leukocytosis and increases in serum alkaline phosphatase, serum aminotransferase, and serum amylase activities and serum bilirubin concentration are likely to be observed. The first diagnostic test is ordinarily US (or CT—equally useful, but more expensive). If the common duct is dilated, the next step is visualization of the biliary tree.
The preferred procedure is magnetic resonance cholangiopancreatography (MRCP). It has the advantage that it is not invasive and does not carry the small but real risks of pancreatitis and cholangitis associated with endoscopic retrograde cholangiopancreatography (ERCP). If there is a normal duct on MRCP then other sources of sepsis can be evaluated, and ERCP may be avoided. If a stone is seen then ERCP is necessary for sphincterotomy and removal of the stone or stones. The initial MRCP can greatly reduce the need for purely diagnostic ERCPs (24). Diagnostic ERCP is still occasionally useful when suspicion of a stone is high, even if the MRCP is apparently normal, and ERCP remains the “standard criterion” for evaluating the biliary tree. (23). The patient's experience during the procedure is essentially the same as it is during other kinds of endoscopy (see Chapter 45) except that ERCP lasts for 30 to 90 minutes and the complication rate is higher (see above).
Percutaneous transhepatic cholangiography (PTC) is most useful in visualizing obstruction of the intrahepatic bile ducts, which can be relieved by stenting in the case of strictures or removal of stones from the small bile ducts. Additionally, PTC is used to visualize the bile ducts in patients who have had a gastrojejunostomy where the sphincter of Oddi is not accessible for ERCP.
Treatment
Therapeutic
Common duct stones should be removed, usually at the time of ERCP by endoscopic sphincterotomy. ERCP is performed in a center where fluoroscopy of the cannulated duct is available. The patient experience during the procedure is essentially the same as it is during other kinds of upper endoscopy (see Chapter 45), except that ERCP usually lasts for 30 to 60 minutes, and may be complicated 5% to 10% of the time by postendoscopic cholangitis, especially if the common duct is manipulated, and by pancreatitis. In an 8-year followup of patients after endoscopic sphincterotomy, papillary stenosis or recurrent bile duct stones occurred in less than 5% of the cases (25).
Although ERCP is the preferred method for removing common bile duct stones, although other approaches are available. Common bile duct exploration and stone removal is possible at either open or laparoscopic cholecystectomy. It is also possible to clear the common bile duct of
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stones using a percutaneous transhepatic catheter. In special situations these alternative approaches have a place, but generally the most expeditious and effective approach is by ERCP.
Cholangitis
Bacterial infection of the biliary tree generally occurs in association with bile duct obstruction caused by choledocholithiasis, tumor, or biliary strictures. The principal symptoms are fever, chills, and abdominal pain. Jaundice is often but not invariably present. On examination, there is abdominal tenderness and often rebound tenderness. Abnormal laboratory tests include leukocytosis and elevations of the serum bilirubin and alkaline phosphatase. Serum aminotransferases may also be moderately elevated. Blood cultures are often positive. The patient may deteriorate rapidly and develop hypotension and changes in mental status. Hospitalization is mandatory for therapy with antibiotics, followed by appropriate relief of biliary obstruction either surgically, by endoscopic sphincterotomy, or by placement of a biliary stent.
Primary sclerosing cholangitis (26) is a chronic inflammation of unknown cause of intrahepatic and extrahepatic bile ducts that leads ultimately to fibrosis and cholestatic liver disease. Most patients are men. There is a very high correlation with concomitant inflammatory bowel disease, most commonly ulcerative colitis. The course of the cholangitis is unpredictable, but patients with advanced disease develop jaundice, right upper quadrant abdominal pain, fever, pruritus, and weight loss and ultimately die of hepatic failure. Diagnosis is made most easily by the demonstration of typical cholangiographic changes during ERCP or MRCP. Adenocarcinoma of the bile ducts is a common complication that occurs in at least 9% to 15% of patients (27). Patients with ulcerative colitis and primary sclerosing cholangitis are also at increased risk of colon cancer, beyond the risk imposed by ulcerative colitis alone (28,29). High doses of ursodeoxycholic acid (20 to 25 mg/kg/day), but not the lower doses commonly used in the treatment of primary biliary cirrhosis (10 to 15 mg/kg/day), improve liver tests and survival in patients with primary sclerosing cholangitis (30). Patients with advanced cirrhosis and jaundice due to primary sclerosing cholangitis should be referred to a transplant center for liver transplantation (see Chapter 47).
Biliary Tract Operations
Primary caregivers should be aware of the mechanics of biliary surgical procedures so that they can inform and reassure patients who are to be referred to a surgeon.
Cholecystectomy
Laparoscopic cholecystectomy has replaced open cholecystectomy as the procedure of choice for the removal of the gallbladder for cholelithiasis and for acute and chronic cholecystitis. Laparoscopic cholecystectomy is performed under general anesthesia. A pneumoperitoneum is established, and a laparoscope and three additional cannulas are inserted through which instruments are placed to remove the gallbladder. Relative contraindications to laparoscopic cholecystectomy include a gangrenous or perforated gallbladder, peritonitis, cholangitis, previous upper abdominal surgery, and cirrhosis (31). Common duct stones are also a contraindication unless they can be extracted by endoscopic sphincterotomy before the cholecystectomy or unless the surgeon is experienced in laparoscopic common duct exploration. Laparoscopic cholecystectomy has the advantage over open cholecystectomy of a shorter hospital stay. In elective cases, the stay is approximately 24 hours, with a return to normal activity in 10 to 14 days. In one study, laparoscopic cholecystectomy needed to be converted to open cholecystectomy in only 4.7% of cases (32). The common reasons for conversion are severe scarring or acute inflammation that obscures the anatomy, adhesions related to prior surgery, aberrant anatomic features that make dissection difficult, and bile duct, bowel, or vascular injuries that occur during surgery. Common duct stones encountered during the procedure can sometimes be removed by laparoscopic choledochoscopy, but otherwise require open common duct exploration or postoperative ERCP. In a reported series, complications occurred in 5.1% of cases (32). The most common complication is wound infection in 1.1% of cases, followed by bile duct injury in 0.5% of cases. Other complications are prolonged ileus, bowel injury, and operative bleeding. Mortality in elective cases is less than 0.1%.
Elective open cholecystectomy has a mortality rate of 0.3% or less. Urgent or emergency operation for acute cholecystitis has a mortality rate of up to 10% depending on whether common duct stones are present. The morbidity of open cholecystectomy is primarily related to superficial wound infection (less than 5% to 7%). Wound infection is more common if the operation lasts longer than 2 hours, the patient is obese or diabetic, and the patient has acute rather than chronic cholecystitis. Other possible but rare (less than 1%) immediate complications of cholecystectomy are postoperative bleeding, postoperative bile leak, injury to biliary ducts (0.1%), and retained common duct stones.
Cholecystostomy
Cholecystostomy may be required in the patient who is critically ill from acute cholecystitis and who has
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associated severe cardiac, pulmonary, or renal disease that contraindicates the use of general anesthesia or of a prolonged operation. Another less often cited indication for cholecystostomy is inability to detect normal biliary anatomy because of a severe inflammatory process near the main bile ducts. Rather than risk possible injury to structures in the porta hepatis, a cholecystostomy may be performed.
A cholecystostomy can be done through a small incision in the right upper quadrant. A large drainage tube is inserted into the gallbladder through a stab wound in the fundus. An attempt is made to remove stones. The tube is brought through the abdominal wall and allowed to drain freely. An attempt should be made to empty the gallbladder of stones before placing the tube. If a stone is impacted at the cystic duct, future cholecystectomy will be necessary or a mucous fistula will persist after the tube is removed. However, if all stones are removed, only 30% to 50% of patients will develop recurrent symptoms of cholelithiasis within 2 years after the tube is removed. The operative mortality is very high from cholecystostomy, not because of the operation but because the patient is critically ill.
Choledochotomy
Common duct exploration or choledochotomy, whether combined with cholecystectomy or as an isolated operation, has a higher morbidity and mortality rate than does simple cholecystectomy. The operation takes longer than cholecystectomy and patients are generally older, two factors important in determining morbidity and mortality. Generally the patient is hospitalized 3 to 5 days longer for common duct exploration than for cholecystectomy alone. A drain (called a T-tube) is generally placed in the common duct at the time of operation. This is done to stent the repair and to allow postoperative imaging to rule out retained stones or other technical problems.
Course After Open Biliary Surgery
Normal Course
The patient is usually discharged 5 to 7 days after an uncomplicated open biliary tract operation. Skin sutures or staples will have been removed, and the patient will be allowed to bathe. Usually patients are requested to avoid driving and sexual relations for 1 week from the day of discharge. Patients are generally advised to avoid heavy (approximately 15 pounds [7 kg] or more) lifting for 4 to 6 weeks. The incidence of incisional hernia (see Chapter 97) is low after a right subcostal oblique incision and slightly higher with a vertical midline or paramedian incision. The patient returns to the surgeon's office for evaluation at 1 and 6 weeks after operation. The wound and the drain sites, if present, should be healed unless there has been wound infection. If a common duct exploration was performed, the T tube is removed in 4 to 6 weeks, assuming the postoperative cholangiogram is normal. The patient should be able to resume an unrestricted regular diet within a few days of operation without difficulty. Stools should be at preoperative frequency and of normal color. Immediate weight loss of 10 to 20 pounds is normal, even in uncomplicated cases. Ten percent of patients have diarrhea for up to 6 weeks but rarely longer than that.
The patient should be expected to complain about pulling sensations in the area of the incision because the right rectus muscle has been divided and resutured. If the subcostal incision was made close to the costal margin, the patient often complains also about discomfort on bending or sitting. The area just below a right subcostal incision is apt to be numb for several months because of interruption of a cutaneous sensory nerve to this area. Sensitivity does return, however, in most cases. It is not surprising to find patients gaining weight after cholecystectomy, especially if they had lost weight preoperatively.
Postcholecystectomy Syndrome
Approximately 90% of patients operated on for symptomatic biliary tract disease become asymptomatic or have trivial symptoms (e.g., occasional dyspepsia). The other 10% may continue to be symptomatic, either because they were treated for the wrong disease or because they have developed a postoperative complication. In the former category are patients who had gallstones but whose symptoms actually emanated from another disease (e.g., chronic pancreatitis, peptic ulcer disease, angina, reflux esophagitis, or irritable bowel syndrome).
Postoperative problems associated with the operation itself include retained common duct stones, and common duct injury with eventual bile duct stricture and recurrent cholangitis. Sphincter of Oddi dysfunction occasionally may be a treatable cause of postcholecystectomy syndrome. The diagnosis is made by showing a decrease in the emptying of the biliary tree by cholecystokinin cholecystography with 99mTc-iminodiacetic derivatives (see Biliary Dyskinesia section) and by demonstrating an elevated sphincter pressure by manometry during ERCP. Sphincterotomy in patients with elevated sphincter pressure results in pain relief in more than 90% of cases (33).
Postcholecystectomy symptoms are occasionally attributed to the cystic duct stump. In the absence of a stone in the stump, this is rarely or ever the cause of the symptoms.
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Specific References
For annotated General References and resources related to this chapter, visit http://www.hopkinsbayview.org/PAMreferences.