Chapter 27 - Biliary Tract

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Chapter 27: Biliary Tract
David A. Harris; Eric G. Sheu
EMBRYOLOGY & ANATOMY
The anlage of the biliary ducts and liver is a diverticulum appearing on the ventral foregut in 3 mm embryos. The cranial portion becomes the liver; a
caudal bud, the ventral pancreas; and an intermediate bud, the gallbladder. The hepatic diverticulum becomes a solid mass of cells that later
recanalizes to form ducts. The smallest, the bile canaliculi, first appear as a basal network between the primitive hepatocytes (Figure 27–1). In most
cases, the common hepatic duct is formed by the union of a single right and left duct. In 25% of individuals, the anterior and posterior divisions of the
right duct join the left duct separately. The origin of the common hepatic duct is close to the liver but always outside its substance. It runs 4 cm before
joining the cystic duct to form the common bile duct. The common duct begins in the hepatoduodenal ligament, passes behind the first portion of the
duodenum, and runs in a groove on the posterior surface of the pancreas before entering the duodenum. Its terminal 1 cm is intimately adherent to
the duodenal wall. The total length of the common duct is about 9 cm.
Figure 27–1.
Scanning electron photomicrograph of a hepatic plate with adjacent sinusoids and sinusoidal microvilli and a bile canaliculus running in the center of
the liver cells. Although their boundaries are indistinct, about four hepatocytes constitute the section of the plate in the middle of the photograph.
Occasional red cells are present within the sinusoids. (Reduced from ×2000.)
In 80%90% of individuals, the main pancreatic duct joins the common duct to form a common channel about 1 cm long. The intraduodenal segment of
the duct is called the hepatopancreatic ampulla, or ampulla of Vater.
The gallbladder is a pearshaped organ adherent to the undersurface of liver segments 4b and 5 by a veil of peritoneum known as the, cystic plate. The
fundus projects 12 cm below the hepatic edge. The gallbladder rarely has a complete peritoneal covering. The lumen of the cystic duct contains a thin
mucosal septum, the spiral valve of Heister, that offers mild resistance to bile flow. The neck of the gallbladder tapers into the narrow cystic duct, which
in 75% of people connects with the common duct. However, biliary anatomy is highly variable. The cystic duct can be short or long and can insert
directly into the right hepatic duct, runs parallel to the hepatic duct, or winds around it before joining the common duct. An accessory right hepatic
duct is also common (Figure 27–2).
Figure 27–2.
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Anatomy of the gallbladder and variations in anatomy of the cystic duct.
mucosal septum, the spiral valve of Heister, that offers mild resistance to bile flow. The neck of the gallbladder tapers into the narrow cystic duct, which
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in 75% of people connects with the common duct. However, biliary anatomy is highly variable. The cystic duct can be short or long and can insert
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directly into the right hepatic duct, runs parallel to the hepatic duct, or winds around it before joining the common duct. An accessory right hepatic
duct is also common (Figure 27–2).
Figure 27–2.
Anatomy of the gallbladder and variations in anatomy of the cystic duct.
In the hepatoduodenal ligament, the hepatic artery is to the left of the common duct, and the portal vein is posterior and medial. The right hepatic
artery usually passes behind the hepatic duct and then gives off the cystic artery before entering the right lobe of the liver, but variations are common.
A replaced right hepatic artery is typically found coming off the superior mesenteric artery and will course along the lateral aspect of the common bile
duct. The cystic artery can also have varied origins, but its termination is usually found by Calot’s node, which sits at the gallbladder infundibularcystic
junction.
PHYSIOLOGY
Bile Flow
Bile is produced from cholesterol at a rate of 5001500 mL/d, and bile salts are actively secreted into the biliary canaliculus. Na+ and water follow
passively to establish isosmolality and electrical neutrality. Lecithin and cholesterol are secreted at rates that correlate with variations in bile salt
output. In addition, bilirubin and a number of other organic anions are actively secreted by the hepatocytes.
The columnar cells of the ducts add a fluid rich in HCO3– to that produced in the canaliculus. This involves active secretion stimulated by secretin,
vasoactive intestinal peptide (VIP), and cholecystokinin (CCK). K+ and water are distributed passively across the ducts (Figure 27–3).
Figure 27–3.
Bile formation. Solid lines into the ductular lumen indicate active transport; dotted lines represent passive diffusion.
vasoactive intestinal peptide (VIP), and cholecystokinin (CCK). K+ and water are distributed passively across the ducts (Figure 27–3).
Figure 27–3.
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Bile formation. Solid lines into the ductular lumen indicate active transport; dotted lines represent passive diffusion.
Between meals, bile is stored in the gallbladder, where it is concentrated at rates of up to 20% per hour. Na+ and either HCO3– or Cl– are actively
transported from its lumen during absorption. The changes in bile composition brought about by the act of concentration are shown in Figure 27–4.
Figure 27–4.
Changes in gallbladder bile composition with time. (Used wth permission from J Dietschy.)
transported from its lumen during absorption. The changes in bile composition brought about by the act of concentration are shown in Figure 27–4.
Figure 27–4.
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Changes in gallbladder bile composition with time. (Used wth permission from J Dietschy.)
Three factors regulate bile flow: hepatic secretion, gallbladder contraction, and choledochal sphincteric resistance. In the fasting state, pressure in the
common bile duct is 510 cm H2O, and bile produced in the liver is diverted into the gallbladder. After a meal, the gallbladder contracts, reaching 25 cm
H2O; the sphincter relaxes; and bile is forced into the duodenum as ductal pressure (1520 cm H2O) exceeds sphincteric resistance.
CCK is the major physiologic stimulus for postprandial gallbladder contraction and relaxation of the sphincter, but vagal impulses facilitate its action.
CCK is released into the bloodstream from the mucosa of the small bowel by fat or lipolytic products in the lumen. Amino acids and small polypeptides
are weaker stimuli, and carbohydrates are ineffective. Bile flow during a meal is augmented by turnover of bile salts in the enterohepatic circulation
and stimulation of ductal secretion by secretin, VIP, and CCK. Motilin stimulates episodic partial gallbladder emptying in the interdigestive phase.
Bile Salts & the Enterohepatic Circulation
Bile salts, lecithin, and cholesterol compose about 90% of the solids in bile, with the remainder consisting of bilirubin, fatty acids, and inorganic salts.
Gallbladder bile contains about 10% solids and has a bile salt concentration between 200 and 300 mmol/L (Figure 27–4).
Bile salts are steroid molecules formed from cholesterol by hepatocytes. The rate of synthesis is under feedback control and can be increased to a
maximum of about 20fold. Two primary bile salts—cholate and chenodeoxycholate—are produced by the liver. Before excretion into bile, they are
conjugated with either glycine or taurine, which enhances water solubility. Intestinal bacteria alter these compounds to produce the secondary bile
salts, deoxycholate and lithocholate. Bile salts function to (1) induce the flow of bile, (2) transport lipids, (3) bind calcium ions in bile, and (4) regulate
metabolic functions. The importance of the last of these is unknown, but it is clear that bile acid signaling is capable of affecting global glucose and fat
metabolism and likely contributes to the metabolic benefits of bariatric operations such as RouxenY gastric bypass and sleeve gastrectomy.
Bile acid molecules are amphipathic—ie, they have hydrophilic and hydrophobic poles. In bile, they form multimolecular aggregates called micelles in
which the hydrophilic poles become aligned to face the aqueous medium. Waterinsoluble lipids, such as cholesterol, can be dissolved within the
hydrophobic centers of bile salt micelles. Molecules of lecithin, which is water insoluble but polar lipid, aggregate into hydrated bilayers that form
vesicles in bile, and they also become incorporated into bile acid micelles to form mixed micelles. Mixed micelles have an increased lipidcarrying
capacity compared with pure bile acid micelles. Cholesterol in bile is transported within the phospholipid vesicles and the bile salt micelles.
Bile salts remain in the intestinal lumen throughout the jejunum, where they participate in fat digestion and absorption (Figure 27–5). Upon reaching
the distal small bowel, they are reabsorbed by an active transport system located in the terminal 200 cm of ileum. Over 95% of bile salts arriving from
the jejunum are transferred by this process into portal vein blood; the remainder enter the colon, where they are converted to secondary bile salts by
colonic bacteria. The entire bile salt pool of 2.54 g circulates twice through the enterohepatic circulation during each meal, and six to eight cycles are
made each day. The normal daily loss of bile salts in the stool amounts to 10%20% of the pool and is restored by hepatic synthesis.
which the hydrophilic poles become aligned to face the aqueous medium. Waterinsoluble lipids, such as cholesterol, can be dissolved within the
hydrophobic centers of bile salt micelles. Molecules of lecithin, which is water insoluble but polar lipid, aggregate into hydrated bilayers that form
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vesicles in bile, and they also become incorporated into bile acid micelles to form mixed micelles. Mixed micelles have an increased lipidcarrying
capacity compared with pure bile acid micelles. Cholesterol in bile is transported within the phospholipid vesicles and the bile salt micelles.
Bile salts remain in the intestinal lumen throughout the jejunum, where they participate in fat digestion and absorption (Figure 27–5). Upon reaching
the distal small bowel, they are reabsorbed by an active transport system located in the terminal 200 cm of ileum. Over 95% of bile salts arriving from
the jejunum are transferred by this process into portal vein blood; the remainder enter the colon, where they are converted to secondary bile salts by
colonic bacteria. The entire bile salt pool of 2.54 g circulates twice through the enterohepatic circulation during each meal, and six to eight cycles are
made each day. The normal daily loss of bile salts in the stool amounts to 10%20% of the pool and is restored by hepatic synthesis.
Figure 27–5.
Enterohepatic circulation of bile salts. (Used with permission from M Tyor.)
Bilirubin
About 250300 mg of bilirubin is excreted each day in the bile, 75% of it from breakdown of red cells in the reticuloendothelial system and 25% from
turnover of hepatic heme and hemoproteins. First, heme is liberated from hemoglobin, and the iron and globin are removed for reuse by the
organism. Biliverdin, the first pigment formed from heme, is reduced to unconjugated bilirubin, the indirectreacting bilirubin of the van den Bergh
test. Unconjugated bilirubin is insoluble in water and is transported in plasma bound to albumin.
Unconjugated bilirubin is extracted from blood by hepatocytes, where it is conjugated with glucuronic acid to form bilirubin diglucuronide, the water
soluble direct bilirubin. Conjugation is catalyzed by glucuronyl transferase, an enzyme on the endoplasmic reticulum. Bilirubin is transported within
the hepatocyte by cytosolic binding proteins, which rapidly deliver the molecule to the canalicular membrane for active secretion into bile. Within bile,
conjugated bilirubin is largely transported in association with mixed lipid micelles.
After entering the intestine, bilirubin is reduced by intestinal bacteria to several compounds known as urobilinogens, which are subsequently oxidized
and converted to pigmented urobilins. The term urobilinogen is often used to refer to both urobilins and urobilinogens.
PATHOGENESIS OF GALLSTONES
More than 20 million people in the United States have gallstones in their gallbladders; about 300,000600,000 operations are performed annually for
this disease, and at least 6000 deaths result from its complications or treatment. The incidence of gallstones increases with age, so that between 50 and
65 years of age, about 20% of women and 5% of men are affected.
After entering the intestine, bilirubin is reduced by intestinal bacteria to several compounds known as urobilinogens, which are subsequently oxidized
and converted to pigmented urobilins. The term urobilinogen is often used to refer to both urobilins and urobilinogens.
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PATHOGENESIS OF GALLSTONES
More than 20 million people in the United States have gallstones in their gallbladders; about 300,000600,000 operations are performed annually for
this disease, and at least 6000 deaths result from its complications or treatment. The incidence of gallstones increases with age, so that between 50 and
65 years of age, about 20% of women and 5% of men are affected.
The gallstones in 75% of patients are composed predominantly (70%95%) of cholesterol and are called cholesterol stones. The remaining 25% are
pigment stones. Regardless of composition, all gallstones give rise to similar clinical sequelae.
Cholesterol Gallstones
Cholesterol gallstones result from secretion of bile supersaturated with cholesterol. Influenced by various factors present in bile, the cholesterol
precipitates from solution, and the newly formed crystals grow to macroscopic stones. Except when the common bile duct is dilated or partially
obstructed, the stones in this disease form exclusively within the gallbladder. Those found in the ducts usually reach that location after passing
through the cystic duct.
The incidence of cholesterol gallstone disease is highest in American Indians, lower in whites, and lowest in blacks, with a twofold gradient from one
group to the next. More than 75% of American Indian women over age 40 are affected. Before puberty, the disease is rare but of equal frequency in
both sexes. Thereafter, women are more commonly affected than men until after menopause, when the discrepancy lessens. Hormonal effects are also
reflected in the increased incidence of gallstones with multiparity and the increased cholesterol saturation of bile and greater incidence of gallstones
following ingestion of oral contraceptives. Obesity is the other major risk factor. The relative risk rises proportionately to the extent of overweight due
to a progressively increasing output of cholesterol in bile.
As noted previously, cholesterol is insoluble and, in bile, must be transported within bile salt micelles and phospholipid (lecithin) vesicles. When the
amount of cholesterol in bile exceeds the cholesterol holding capacity, cholesterol crystals begin to precipitate from the phospholipid vesicles.
The secretion of bile salt and cholesterol into bile is linked. Bile salt elutes cholesterol from the hepatocyte membrane during passage into the bile
canaliculus. At higher bile salt output levels, the amount of cholesterol relative to bile salt entering bile decreases. This means that during low bile flow
(eg, during fasting), bile holding capacity for cholesterol is more saturated than during high bile flow. In fact, almost half of persons in Western cultures
have bile supersaturated with cholesterol in the morning after an overnight fast. The bile salt pool in patients with cholesterol gallstone disease is
about half the size of that of normal subjects, but this is a result of the gallstone disease (eg, gallstones displace bile in the gallbladder) and not a
cause.
The occurrence of cholesterol gallstone disease requires cholesterol supersaturation of bile, but that in itself is not sufficient. Cholesterol in
supersaturated bile from individuals without gallstone disease precipitates spontaneously at a much slower rate than does the cholesterol in similar
bile from patients with gallstones. Furthermore, among individuals with supersaturated bile, only those with gallstone disease demonstrate
cholesterol crystal formation in vivo. These observations are the result of specific bile proteins that either stabilize or destabilize cholesterolladen
phospholipid vesicles. For gallstone formation, the pronucleating factors (eg, immunoglobulin, mucus glycoprotein, fibronectin, orosomucoid)
appear to be more important than the antinucleating factors (eg, glycoprotein, apolipoprotein, cytokeratin). Variations in these proteins may be the
critical factor determining which of the many individuals with saturated bile develop gallstones.
The fact that gallstones form almost exclusively in the gallbladder, even though the composition of hepatic bile is abnormal, underscores the
important role of the gallbladder in gallstone pathogenesis. This includes concentrating the bile, providing nidi (eg, small grains of pigment) for
crystallization of cholesterol, supplying mucoprotein to paste the stones together, and serving as an area of stasis to allow stone formation and
growth.
Pigment Stones
Pigment stones account for 25% of gallstones in the United States and 60% of those in Japan. Pigment stones are black to dark brown, 25 mm in
diameter, and amorphous. They are composed of a mixture of calcium bilirubinate, complex bilirubin polymers, bile acids, and other unidentified
substances. About 50% are radiopaque, and in the United States, they constitute twothirds of all radiopaque gallstones. The incidence is similar in
men and women and in blacks and whites. Pigment stones are rare in American Indians.
Predisposing factors are cirrhosis, bile stasis (eg, a strictured or markedly dilated common duct), and chronic hemolysis. Some patients with pigment
stones have increased concentrations of unconjugated bilirubin in their bile. Scanning electron microscopy demonstrates that about 90% of pigment
stones are composed of dense mixtures of bacteria and bacterial glycocalyx along with pigment solids. This suggests that bacteria have a primary role
in pigment gallstone formation, and it also helps to explain why patients with pigment gallstone disease have sepsis more often than do those with
cholesterol gallstone disease. It seems likely that bacterial βglucuronidase is responsible for deconjugating the soluble bilirubindiglucuronide to
insoluble unconjugated bilirubin, which subsequently becomes agglomerated by glycocalyx into macroscopic stones.
diameter, and amorphous. They are composed of a mixture of calcium bilirubinate, complex bilirubin polymers, bile acids, and other unidentified
substances. About 50% are radiopaque, and in the United States, they constitute twothirds of all radiopaque gallstones. The incidence is similar in
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men and women and in blacks and whites. Pigment stones are rare in American Indians.
Predisposing factors are cirrhosis, bile stasis (eg, a strictured or markedly dilated common duct), and chronic hemolysis. Some patients with pigment
stones have increased concentrations of unconjugated bilirubin in their bile. Scanning electron microscopy demonstrates that about 90% of pigment
stones are composed of dense mixtures of bacteria and bacterial glycocalyx along with pigment solids. This suggests that bacteria have a primary role
in pigment gallstone formation, and it also helps to explain why patients with pigment gallstone disease have sepsis more often than do those with
cholesterol gallstone disease. It seems likely that bacterial βglucuronidase is responsible for deconjugating the soluble bilirubindiglucuronide to
insoluble unconjugated bilirubin, which subsequently becomes agglomerated by glycocalyx into macroscopic stones.
JAUNDICE
Jaundice is categorized as prehepatic, hepatic, or posthepatic, depending on the site of the underlying disease. Hemolysis, the most common cause of
prehepatic jaundice, involves increased production of bilirubin. Less common causes of prehepatic jaundice are Gilbert disease and the CriglerNajjar
syndrome.
Hepatic parenchymal jaundice is subdivided into hepatocellular and cholestatic types. The former includes acute viral hepatitis and chronic alcoholic
cirrhosis. Some cases of intrahepatic cholestasis may be indistinguishable clinically and biochemically from cholestasis due to bile duct obstruction.
Primary biliary cirrhosis, toxic drug jaundice, cholestatic jaundice of pregnancy, and postoperative cholestatic jaundice are the most common forms.
Extrahepatic jaundice most often results from biliary obstruction by a malignant tumor, choledocholithiasis, or biliary stricture. Pancreatic pseudocyst,
chronic pancreatitis, sclerosing cholangitis, metastatic cancer, and duodenal diverticulitis are less common causes.
The cause of jaundice can be ascertained in the majority of patients from clinical and laboratory findings alone. In the remainder, transhepatic
cholangiography (THC) or endoscopic retrograde cholangiopancreatography (ERCP) and ultrasound or computed tomography (CT) scans will be
necessary. The indications for these tests are discussed in later sections.
History
The age, gender, and parity of the patient and possible deleterious habits should be noted. Most cases of infectious hepatitis occur in patients under
age 30. A history of drug addiction may suggest serum hepatitis transmitted by shared hypodermic equipment. Chronic alcoholism can usually be
documented in patients with cirrhosis, and acute jaundice in alcoholics usually follows a recent binge. Obstructing gallstones or tumors are more
common in older people.
Patients with jaundice due to choledocholithiasis may have associated biliary colic, fever, and chills and may report previous similar attacks. In
contrast, pain is either absent in malignant obstruction or deepseated and dull. Pain in the region of the liver is frequently experienced in the early
stages of viral hepatitis and acute alcoholic liver injury. The patient with extrahepatic obstruction may report that stools have become lighter in color
and the urine dark. Cholestatic diseases are often accompanied by pruritus. The cause remains obscure; itching does not correlate with bile salt levels
in the skin, as was once believed.
Physical Examination
Hepatomegaly is common in both hepatic and posthepatic jaundice. In some cases, palpation of the liver may suggest cirrhosis or metastatic cancer,
but impressions of this kind are unreliable. Secondary stigmata of cirrhosis usually accompany acute alcoholic jaundice; palmar erythema, spider
angiomas, ascites, collateral veins on the abdominal walls, and splenomegaly suggest cirrhosis. A nontender, palpable gallbladder in a jaundiced
patient suggests malignant obstruction of the common duct (Courvoisier sign), but absence of a palpable gallbladder is of little significance in ruling
out cancer.
Laboratory Tests
In hemolytic disease, the increased bilirubin is principally in the unconjugated indirect fraction. Because unconjugated bilirubin is insoluble in water,
the jaundice in hemolysis is acholuric. The total bilirubin in hemolysis rarely exceeds 45 mg/dL because the rate of excretion increases as the bilirubin
concentration rises and a plateau is quickly reached. Greater values suggest concomitant hepatic parenchymal disease.
Jaundice due to hepatic parenchymal disease is characterized by elevations of both conjugated and unconjugated serum bilirubin. An increase in the
conjugated fraction always signifies disease within the hepatobiliary system. The direct bilirubin predominates in about half of cases of hepatic
parenchymal disease.
Both intrahepatic cholestasis and extrahepatic obstruction raise the direct bilirubin fraction, although the indirect fraction also increases somewhat.
Because direct bilirubin is water soluble, bilirubinuria develops. With complete extrahepatic obstruction, the total bilirubin rises to a plateau of 2530
mg/dL, at which point loss in the urine equals the additional daily production. Higher values suggest concomitant hemolysis or decreased renal
the jaundice in hemolysis is acholuric. The total bilirubin in hemolysis rarely exceeds 45 mg/dL because the rate of excretion increases as the bilirubin
concentration rises and a plateau is quickly reached. Greater values suggest concomitant hepatic parenchymal disease.
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Jaundice due to hepatic parenchymal disease is characterized by elevations of both conjugated and unconjugated serum bilirubin. An increase in the
conjugated fraction always signifies disease within the hepatobiliary system. The direct bilirubin predominates in about half of cases of hepatic
parenchymal disease.
Both intrahepatic cholestasis and extrahepatic obstruction raise the direct bilirubin fraction, although the indirect fraction also increases somewhat.
Because direct bilirubin is water soluble, bilirubinuria develops. With complete extrahepatic obstruction, the total bilirubin rises to a plateau of 2530
mg/dL, at which point loss in the urine equals the additional daily production. Higher values suggest concomitant hemolysis or decreased renal
function. Obstruction of a single hepatic duct does not usually cause jaundice.
In extrahepatic obstruction caused by neoplasms, the serum bilirubin usually exceeds 10 mg/dL, and the average concentration is about 18 mg/dL.
Obstructive jaundice due to common duct stones often produces transient bilirubin increases in the range of 24 mg/dL, and the level rarely exceeds 15
mg/dL. Serum bilirubin values in patients with alcoholic cirrhosis and acute viral hepatitis vary widely in relation to the severity of the parenchymal
damage.
In extrahepatic obstruction, modest rises of aspartate aminotransferase (AST) levels are common, but levels as high as 1000 units/L are seen (although
rarely) in patients with common duct stones and cholangitis. In the latter patients, the high values last for only a few days and are associated with
increases in lactate dehydrogenase (LDH) concentrations. In general, AST levels above 1000 units/L suggest viral hepatitis.
Serum alkaline phosphatase comes from three sites: liver, bone, and intestine. In normal subjects, liver and bone contribute about equally, and the
intestinal contribution is small. Hepatic alkaline phosphatase is a product of the epithelial cells of the cholangioles, and increased alkaline
phosphatase levels associated with liver disease result from increased enzyme production. Alkaline phosphatase levels increase with intrahepatic
cholestasis, cholangitis, or extrahepatic obstruction. Because the elevation is from overproduction, it may occur with focal hepatic lesions in the
absence of jaundice. For example, a solitary hepatic metastasis or pyogenic abscess in one lobe or a tumor obstructing only one hepatic duct may fail
to obstruct enough hepatic parenchyma to cause jaundice but usually is associated with increased alkaline phosphatase. In cholangitis with
incomplete extrahepatic obstruction, serum bilirubin levels may be normal or mildly elevated, but serum alkaline phosphatase may be very high.
Bone disease may complicate the interpretation of abnormal alkaline phosphatase levels (Figure 27–6). If one suspects that the increased serum
enzyme may be from bone, serum calcium, phosphorus, and 5′nucleotidase or leucine aminopeptidase levels should be determined. These last two
enzymes are also produced by cholangioles and are elevated in cholestasis, but their serum concentrations remain unchanged with bone disease.
Figure 27–6.
Range of alkaline phosphatase values in various hepatobiliary disorders.
enzymes are also produced by cholangioles and are elevated in cholestasis, but their serum concentrations remain unchanged with bone disease.
Figure 27–6.
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Range of alkaline phosphatase values in various hepatobiliary disorders.
Changes in serum protein levels may reflect hepatic parenchymal dysfunction. In cirrhosis, the serum albumin falls and the globulins increase. Serum
globulins reach high values in some patients with primary biliary cirrhosis. Biliary obstruction generally produces no changes unless secondary biliary
cirrhosis has developed.
Diagnosis
The principal diagnostic objective is to distinguish surgical (obstructive) from nonsurgical jaundice. The history, physical examination, and basic
laboratory data allow an accurate diagnosis to be made in most cases without invasive tests. Most patients with jaundice are not critically ill when first
examined; thus, diagnosis and therapy may be conducted in a stepwise fashion. However, severe or worsening cholangitis requires urgent
intervention. If the jaundice is mild and recent, it often passes within 2448 hours, at which time adjunct tests can be ordered to verify gallstone
disease.
A comprehensive discussion of available imaging modalities is found in the following sections. In patients with persistent jaundice, the first test is
usually an abdominal ultrasound to allow for assessment of ductal dilation and cholelithiasis. Lesions may be further delineated by magnetic
resonance cholangiopancreatography (MRCP), ERCP, endoscopic ultrasound (EUS), or THC. ERCP is preferable when the lower end of the duct is
believed to be obstructed or if the presence of choledocholithiasis is likely. THC is usually preferred for proximal lesions because it gives better
opacification of the ducts proximal to the obstruction and therefore provides more information that can be used in planning surgery. If the clinical
presentation suggests neoplastic obstruction, magnetic resonance imaging (MRI) or multiphase, thinslice CT scan will allow improved definition of the
mass, surrounding structures, and general location of bile duct obstruction.
DIAGNOSTIC EXAMINATION OF THE BILIARY TREE
Abdominal Ultrasound
Due to its low risk and high sensitivity and specificity, transabdominal ultrasonography is the primary adjunct test of choice for the detection of
cholelithiasis and cholecystitis and evaluation for bile duct dilation. Cholecystitis is suggested by distension of the gallbladder, the presence of stones,
pericholecystic edema, and the presence of a sonographic Murphy sign. In the investigation of gallbladder disease, falsepositive diagnoses for stones
are rare, and falsenegative reports due to small stones or a contracted gallbladder occur in only 5% of patients examined by realtime ultrasound.
Ultrasound usually misses stones in the common duct, but a dilated common bile duct can hint toward the presence of choledocholithiasis and
suggest the need for further intervention or imaging to confirm the presence of choledocholithiasis.
Abdominal Ultrasound
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Due to its low risk and high sensitivity and specificity, transabdominal ultrasonography is the primary adjunct test of choice for the detection of
cholelithiasis and cholecystitis and evaluation for bile duct dilation. Cholecystitis is suggested by distension of the gallbladder, the presence of stones,
pericholecystic edema, and the presence of a sonographic Murphy sign. In the investigation of gallbladder disease, falsepositive diagnoses for stones
are rare, and falsenegative reports due to small stones or a contracted gallbladder occur in only 5% of patients examined by realtime ultrasound.
Ultrasound usually misses stones in the common duct, but a dilated common bile duct can hint toward the presence of choledocholithiasis and
suggest the need for further intervention or imaging to confirm the presence of choledocholithiasis.
The ultrasonographer occasionally reports that the gallbladder contains “sludge.” This material is sonographically opaque, does not cast an acoustic
shadow, and forms a dependent layer in the gallbladder. On clinical analysis, it is a fine precipitate of calcium bilirubinate. Sludge may accompany
gallstone disease or may be a solitary finding. It is observed in a variety of clinical settings, many of which are characterized by gallbladder stasis. By
itself, sludge is not an indication for cholecystectomy.
Abdominal Computed Tomography
Patients presenting with abdominal pain with an unclear history and leukocytosis are often sent for abdominal CT. Although this is not the imaging
modality of choice for evaluation of the gallbladder or biliary tree, it does have good specificity and sensitivity for the detection of acute cholecystitis.
For the evaluation of the patient with persistent jaundice, it allows for superior detection of pancreatic and distal obstructive pathology.
Radionuclide Scan (Hepatobiliary Iminodiacetic Acid Scan)
Technetium99m–labeled derivatives of iminodiacetic acid (IDA) are excreted in high concentration in bile and produce excellent gamma camera
images. Following intravenous injection of the radionuclide, imaging of the bile ducts and gallbladder normally appears within 1530 minutes and
imaging of the intestine within 60 minutes. In patients with acute right upper quadrant pain and tenderness, a good image of the bile duct
accompanied by no image of the gallbladder indicates cystic duct obstruction and strongly supports a diagnosis of acute cholecystitis. The test is easy
to perform and is occasionally a useful method of confirming this diagnosis in patients with equivocal history and imaging for acute cholecystitis.
In addition, if biliary dyskinesia is suspected, a hepatobiliary IDA (HIDA) scan can be used to measure the gallbladder ejection fraction after CCK
stimulation. Finally, HIDA scanning is useful in the postcholecystectomy patient to diagnose a biliary leak, although the scan usually lacks the fidelity to
determine the exact location of the leak.
Magnetic Resonance Cholangiopancreatography
MRCP and ERCP are the two most sensitive (approximately 90% for MRCP and near 100% for ERCP) and specific (approximately 90% for MRCP and 100%
for ERCP) modalities for the evaluation of choledocholithiasis. MRCP has resolution to detect stones as small as 2 mm. In patients in whom
choledocholithiasis is highly likely, forgoing MRCP for ERCP is prudent because ERCP affords the opportunity for intervention. However, if the
diagnosis is in question, MRCP offers the advantage of being noninvasive, without the risk of ERCPrelated complications such as pancreatitis,
bleeding, or perforation.
Endoscopic Retrograde Cholangiopancreatography
ERCP involves cannulating the sphincter of Oddi under direct vision through a sideviewing duodenoscope. It requires special training involving more
than familiarity with the use of fiberoptic endoscopes. Usually it is possible to opacify the pancreatic and bile ducts. It is the preferred method of
examining the biliary tree in patients with presumed choledocholithiasis or obstructing lesions in the periampullary region and provides access for
therapeutic intervention.
Endoscopic Ultrasound
Using specialized echoendoscopes, EUS allows highresolution imaging of the biliary tree, pancreas, and stomach. EUS can be used to guide biopsy as
well as more advanced interventions. For choledocholithiasis, EUS has a sensitivity of 89%94% and a specificity of 94%95%. For small stones in
particular, EUS may be more sensitive than MRCP. If choledocholithiasis is detected on EUS, therapeutic ERCP can be immediately performed.
Percutaneous Transhepatic Cholangiography
Percutaneous THC is performed by passing a fine needle through the right lower rib cage and the hepatic parenchyma and into the lumen of a bile
duct. Watersoluble contrast material is injected, and fluoroscopy is performed.
The technical success is related to the degree of dilatation of the intrahepatic bile ducts. THC is especially valuable in demonstrating the biliary
anatomy in patients with benign biliary strictures, malignant lesions of the proximal bile duct, or when ERCP has been unsuccessful. Patients should be
premedicated with antibiotics regardless of whether they have cholangitis—septic shock has been produced by sudden inoculation of organisms from
bile into the systemic circulation. Otherwise, the contraindications are the same as for percutaneous liver biopsy.
particular, EUS may be more sensitive than MRCP. If choledocholithiasis is detected on EUS, therapeutic ERCP can be immediately performed.
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Percutaneous Transhepatic Cholangiography
Percutaneous THC is performed by passing a fine needle through the right lower rib cage and the hepatic parenchyma and into the lumen of a bile
duct. Watersoluble contrast material is injected, and fluoroscopy is performed.
The technical success is related to the degree of dilatation of the intrahepatic bile ducts. THC is especially valuable in demonstrating the biliary
anatomy in patients with benign biliary strictures, malignant lesions of the proximal bile duct, or when ERCP has been unsuccessful. Patients should be
premedicated with antibiotics regardless of whether they have cholangitis—septic shock has been produced by sudden inoculation of organisms from
bile into the systemic circulation. Otherwise, the contraindications are the same as for percutaneous liver biopsy.
Intraoperative Imaging
Patients with cholecystitis and equivocal imaging or laboratory testing can undergo intraoperative imaging to assess for common bile duct stones.
Intraoperative cholangiogram (IOC) is performed by direct cannulation of the cystic duct or gallbladder infundibulum during laparoscopic or open
cholecystectomy. Contrast material is injected through the cannulation, and fluoroscopy is used to assess for common bile duct stones. Stones
present in the duct can sometimes be cleared by flushing and glucagon administration to promote relaxation of the sphincter of Oddi.
Some have recommended routine use of IOC as a means to limit and detect bile duct injuries during cholecystectomy. During routine use of IOC,
2%10% of patients will have a common bile duct stone, 10% of which will not have been suspected preoperatively, and the majority of incidentally
detected common bile duct stones will pass spontaneously without clinical sequelae.
Intraoperative ultrasound is another imaging modality that can be performed to define biliary and vascular anatomy and has a high sensitivity and
specificity for the detection of common bile duct stones. However, unlike IOC, ultrasound does not afford the ability to intervene upon any identified
pathology. The learning curve for this modality is steep, with upward of 100 cases needed for mastery.
DISEASES OF THE GALLBLADDER & BILE DUCTS
ASYMPTOMATIC GALLSTONES
Data on the prevalence of gallstones in the United States indicate that only about 30% of people with cholelithiasis come to surgery. Symptoms of
gallstone disease generally do not change in severity. Each year, about 2% of patients with asymptomatic gallstones develop symptoms, usually biliary
colic rather than one of the complications of gallstone disease. Patients with chronic biliary colic tend to have symptoms of the same level of severity
and frequency. The present practice of operating only on symptomatic patients, leaving the millions without symptoms alone, seems appropriate. A
question is often raised about what to advise the asymptomatic patient found to have gallstones during the course of unrelated studies. The presence
of the following portends a more serious course and should probably serve as a reason for consideration of prophylactic cholecystectomy in the
asymptomatic patient: (1) large stones (> 1 cm in diameter), because they progress to symptomatic disease more often than small stones; (2) calcified
gallbladder, as it may be associated with carcinoma; and (3) enlarging or > 1 cm gallbladder polyps, given the potential risk of malignancy. However,
most asymptomatic patients have no special features. If coexistent cardiopulmonary or other problems increase the risk of surgery, operation should
not be considered. For the average asymptomatic patient, it is not reasonable to make a strong recommendation for cholecystectomy. The tendency,
however, is to operate on younger patients and temporize in the elderly.
BILIARY DYSKINESIA
Patients with histories consistent with biliary colic, but in the absence of stone disease may have a functional gallbladder disorder. Typically, after an
overnight fast, a HIDA scan in the presence of CCK is performed over a 45minute period. A gallbladder ejection fraction less than 40% is considered
evidence of gallbladder dyskinesia. Reproduction of symptoms with administration of CCK may also support the diagnosis of biliary dyskinesia. False
positives are seen in patients on opioids, with diabetes, and on calcium channel blockers, oral contraceptives, or other medications. In patients with
recurring, biliarytype pain and a HIDACCK test consistent with dyskinesia, cholecystectomy may be beneficial.
GALLSTONES & CHRONIC CHOLECYSTITIS (BILIARY COLIC)
ESSENTIALS OF DIAGNOSIS
Episodic abdominal pain
Dyspepsia
Gallstones on cholecystography or ultrasound scan
evidence of gallbladder dyskinesia. Reproduction of symptoms with administration of CCK may also support the diagnosis of biliary dyskinesia. False
positives are seen in patients on opioids, with diabetes, and on calcium channel blockers, oral contraceptives, or other medications. In patients with
recurring, biliarytype pain and a HIDACCK test consistent with dyskinesia, cholecystectomy may be beneficial. Access Provided by:
GALLSTONES & CHRONIC CHOLECYSTITIS (BILIARY COLIC)
Episodic abdominal pain
Dyspepsia
Gallstones on cholecystography or ultrasound scan
General Considerations
Chronic cholecystitis is the most common form of symptomatic gallbladder disease and is associated with gallstones in nearly every case. In general,
the term cholecystitis is applied whenever gallstones are present regardless of the histologic appearance of the gallbladder. Repeated minor episodes
of obstruction of the cystic duct cause intermittent biliary colic and contribute to inflammation and subsequent scar formation. Gallbladders from
symptomatic patients with gallstones who have never had an attack of acute cholecystitis are of two types: (1) In some, the mucosa may be slightly
flattened, but the wall is thin and unscarred and, except for the stones, appears normal. (2) Others exhibit obvious signs of chronic inflammation, with
thickening, cellular infiltration, loss of elasticity, and fibrosis. The clinical history in these two groups cannot always be distinguished, and
inflammatory changes may also be found in patients with asymptomatic gallstones.
Clinical Findings
A. Symptoms and Signs
Biliary colic, the most characteristic symptom, is caused by transient gallstone obstruction of the cystic duct. The pain usually begins abruptly and
subsides gradually, lasting for a few minutes to several hours. The pain of biliary colic is usually steady—not intermittent, like that of intestinal colic. In
some patients, attacks occur postprandially; in others, there is no relationship to meals. The frequency of attacks is quite variable, ranging from nearly
continuous trouble to episodes many years apart. Nausea and vomiting may accompany the pain.
Biliary colic is usually felt in the right upper quadrant, but epigastric and left abdominal pain are common, and some patients experience precordial
pain. The pain may radiate around the costal margin into the back or may be referred to the region of the scapula. Pain on top of the shoulder is
unusual and suggests direct diaphragmatic irritation. During an attack, there may be tenderness in the right upper quadrant, and rarely, the
gallbladder is palpable.
Fatty food intolerance, dyspepsia, indigestion, heartburn, flatulence, and nausea are other symptoms associated with gallstone disease. Because they
are also frequent in the general population, their presence in any given patient may only be incidental to the gallstones.
B. Laboratory Findings
An ultrasound of the gallbladder should usually be the first test. Gallstones can be demonstrated in about 95% of cases, and a positive reading for
gallstones is rarely in error. About 2% of patients with gallstone disease have normal ultrasound studies.
Differential Diagnosis
Gallbladder colic may be strongly suggested by the history, but the clinical impression should always be verified by an ultrasound study. Biliary colic
may simulate the pain of duodenal ulcer, hiatal hernia, pancreatitis, and myocardial infarction. It has been suggested that biliary colic may sometimes
aggravate cardiac disease, but angina pectoris or an abnormal electrocardiogram (ECG) should rarely be indications for cholecystectomy.
Rightsided radicular pain in the T6T10 dermatomes may be confused with biliary colic. Osteoarthritic spurs, vertebral lesions, or tumors may be
shown on xrays of the spine or may be suggested by hyperesthesia of the abdominal skin.
A search for esophageal spasm, hiatal hernia, peptic ulcer, or gastric tumors may be warranted. In some patients, an irritable colon syndrome may be
mistaken for gallbladder discomfort. Carcinoma of the cecum or ascending colon may be overlooked on the assumption that postprandial pain in
these conditions is due to gallstones.
Complications
Chronic cholecystitis predisposes to acute cholecystitis, common duct stones, and adenocarcinoma of the gallbladder. The longer the stones have
been present, the higher is the incidence of all of these complications. Complications are infrequent, however, and the presence of gallstones is not
Rightsided radicular pain in the T6T10 dermatomes may be confused with biliary colic. Osteoarthritic spurs, vertebral lesions, or tumors may be
shown on xrays of the spine or may be suggested by hyperesthesia of the abdominal skin. RED de Universidades Anáhuac
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A search for esophageal spasm, hiatal hernia, peptic ulcer, or gastric tumors may be warranted. In some patients, an irritable colon syndrome may be
mistaken for gallbladder discomfort. Carcinoma of the cecum or ascending colon may be overlooked on the assumption that postprandial pain in
these conditions is due to gallstones.
Complications
Chronic cholecystitis predisposes to acute cholecystitis, common duct stones, and adenocarcinoma of the gallbladder. The longer the stones have
been present, the higher is the incidence of all of these complications. Complications are infrequent, however, and the presence of gallstones is not
reason enough for prophylactic cholecystectomy in a person with asymptomatic or mildly symptomatic disease.
Treatment
A. Medical Treatment
Avoidance of offending foods may be helpful. Dissolution with ursodiol is generally not recommended due to poor efficacy.
B. Surgical Treatment
Cholecystectomy is indicated in most patients with symptoms. The procedure can be scheduled at the patient’s convenience, within weeks or months
after diagnosis. Active concurrent disease that increases the risk of surgery should be treated before operation. In some chronically ill patients, surgery
should be deferred indefinitely.
Cholecystectomy is most often performed laparoscopically, but when the laparoscopic approach is contraindicated or unsuccessful, it may be
performed through a laparotomy. The difference consists of 4 fewer days in the hospital and fewer weeks off work when done laparoscopically.
Regardless of how it is done, operative cholangiography may be included to evaluate for common duct stones. If stones are found, common duct
exploration may be performed (see section on choledocholithiasis).
Prognosis
Serious complications and deaths related to the operation itself are rare. The operative death rate is about 0.1% in patients under age 50 and about
0.5% in patients over age 50. Most deaths occur in patients recognized preoperatively to have increased risks. The operation relieves symptoms in 95%
of cases.
The historical risk of common bile duct injury is roughly 0.4%. To reduce this catastrophic event, many societies have advocated safe surgical
dissection in the form of the “critical view of safety.” The goal of this method is to identify the cystic duct and artery prior to division of any tubular
structures. The critical view of safety is obtained by dissection of the lower third of the gallbladder free from the liver and identifying two, and only two,
tubular structures between the gallbladder and the hepatoduodenal ligament. Studies have shown a reduction in common bile duct injury to
0%0.03%.
Gurusamy KS, Koti R, Fusai G, et al: Early versus delayed laparoscopic cholecystectomy for uncomplicated biliary colic. Cochrane Database Syst Rev .
2013;6:CD007196.
ACUTE CHOLECYSTITIS
Acute right upper quadrant pain and tenderness
Fever and leukocytosis
Palpable gallbladder in onethird of cases
Sonographic Murphy sign with gallbladder distension, wall thickening, stones, pericholecystic fluid
Nonopacified gallbladder on radionuclide excretion scan
In 80% of cases, acute cholecystitis results from obstruction of the cystic duct by a gallstone impacted in the Hartmann pouch. The gallbladder
2013;6:CD007196.
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ACUTE CHOLECYSTITIS
Acute right upper quadrant pain and tenderness
Fever and leukocytosis
Palpable gallbladder in onethird of cases
Sonographic Murphy sign with gallbladder distension, wall thickening, stones, pericholecystic fluid
Nonopacified gallbladder on radionuclide excretion scan
In 80% of cases, acute cholecystitis results from obstruction of the cystic duct by a gallstone impacted in the Hartmann pouch. The gallbladder
becomes inflamed and distended, creating abdominal pain and tenderness. The natural history of acute cholecystitis varies, depending on whether
the obstruction becomes relieved, the extent of secondary bacterial invasion, the age of the patient, and the presence of other aggravating factors such
as diabetes mellitus. Most attacks resolve spontaneously without surgery or other specific therapy, but some progress to abscess formation or free
perforation with generalized peritonitis.
The pathologic changes in the gallbladder evolve in a typical pattern. Subserosal edema and hemorrhage and patchy mucosal necrosis are the first
changes. Later, polymorphonuclear leukocytes appear. The final stage involves development of fibrosis. Gangrene and perforation may occur as early
as 3 days after onset, but most perforations occur during the second week. In cases that resolve spontaneously, acute inflammation has largely cleared
by 4 weeks, but some residual evidence of inflammation may last for several months. About 90% of gallbladders removed during an acute attack show
chronic scarring, although many of these patients deny having had any previous symptoms.
The cause of acute cholecystitis is still partially conjectural. Obstruction of the cystic duct is present in most cases, but in experimental animals, cystic
duct obstruction does not result in acute cholecystitis unless the gallbladder is filled with concentrated bile or bile saturated with cholesterol. There is
also evidence that trauma from gallstones releases phospholipase from the mucosal cells of the gallbladder. This is followed by conversion of lecithin
in bile to lysolecithin, which is a toxic compound that may cause more inflammation. Bacteria have a minor role in the early stages of acute
cholecystitis, even though most complications of the disease involve suppuration.
Clinical Findings
The first symptom is abdominal pain in the epigastrium or right upper quadrant, sometimes associated with referred pain in the region of the right
scapula. In 75% of cases, the patient will have had previous attacks of biliary colic, at first indistinguishable from the present illness. However, in acute
cholecystitis, the pain persists and becomes associated with abdominal tenderness. Nausea and vomiting are present in about half of patients, but the
vomiting is rarely severe. Mild icterus occurs in 10% of cases. The temperature usually ranges from 38°C to 38.5°C. High fever and chills are uncommon
and should suggest the possibility of complications or an incorrect diagnosis.
Right upper quadrant tenderness is present, and in about a third of patients, the gallbladder is palpable (often in a position lateral to its normal one).
Voluntary guarding during examination may prevent detection of an enlarged gallbladder. In others, the gallbladder is not enlarged because scarring
of the wall restricts distention. If instructed to breathe deeply during palpation in the right subcostal region, the patient experiences accentuated
tenderness and sudden inspiratory arrest (Murphy sign).
The leukocyte count is usually elevated, but normal counts are common. A mild elevation of the serum bilirubin (in the range of 24 mg/dL) is common,
presumably due to secondary inflammation of the common duct by the contiguous gallbladder. Bilirubin values above this range would most likely
indicate the associated presence of common duct stones. A mild increase in alkaline phosphatase may accompany the attack. Occasionally, the serum
amylase concentration transiently reaches 1000 units/dL or more.
C. Imaging Studies
As stated earlier, right upper quadrant ultrasound is the imaging modality of choice. The presence of stones or sludge, thickening of the gallbladder
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The leukocyte count is usually elevated, but normal counts are common. A mild elevation of the serum bilirubin (in the range of 24 mg/dL) is common,
presumably due to secondary inflammation of the common duct by the contiguous gallbladder. Bilirubin values above this range would most likely
indicate the associated presence of common duct stones. A mild increase in alkaline phosphatase may accompany the attack. Occasionally, the serum
amylase concentration transiently reaches 1000 units/dL or more.
C. Imaging Studies
As stated earlier, right upper quadrant ultrasound is the imaging modality of choice. The presence of stones or sludge, thickening of the gallbladder
wall, pericholecystic edema, and a sonographic Murphy sign are consistent with acute cholecystitis. Usually, along with a careful history and physical
exam, ultrasound is the only test needed to make the diagnosis of acute cholecystitis.
If additional diagnostic information is desirable (eg, if ultrasound is equivocal or negative), a radionuclide excretion scan (eg, HIDA scan) should be
performed. This test cannot demonstrate gallstones, but if the gallbladder is imaged, acute cholecystitis is ruled out except in rare cases of acalculous
cholecystitis (see later section; the test is positive in most cases of acute acalculous cholecystitis). Imaging of the duct but not the gallbladder supports
the diagnosis of acute cholecystitis. A few false positives are seen in advanced gallstone disease without acute inflammation and in acute biliary
pancreatitis. The presence of an elevated bilirubin and a dilated common bile duct should suggest the presence of choledocholithiasis (see later in
chapter).
The differential diagnosis includes other common causes of acute upper abdominal pain and tenderness. An acute peptic ulcer with or without
perforation might be suggested by a history of epigastric pain relieved by food or antacids. Most cases of perforated ulcer demonstrate free air under
the diaphragm on xray. An abdominal CT could provide more anatomic detail.
Acute pancreatitis can be confused with acute cholecystitis, especially if cholecystitis is accompanied by an elevated lipase level. Furthermore, HIDA
scans fail to outline the gallbladder in most cases of acute biliary pancreatitis. Sometimes the two diseases coexist, but pancreatitis should not be
accepted as a second diagnosis without specific findings.
Acute appendicitis in patients with a high cecum may closely simulate acute cholecystitis.
Severe right upper quadrant pain with high fever and local tenderness may develop in acute gonococcal perihepatitis (FitzHughCurtis syndrome).
Clues to the proper diagnosis may be found in tenderness in the adnexa, vaginal discharge that shows gonococci on a gramstained smear, and a
disparity between the patient’s high fever and her general lack of toxicity.
Complications
The major complications of acute cholecystitis are empyema and perforation.
A. Empyema
In empyema (suppurative cholecystitis), the gallbladder contains frank pus, and the patient becomes more toxic, with high spiking fever (3940°C),
chills, and leukocytosis greater than 15,000/μL. Parenteral antibiotics should be given, and percutaneous cholecystostomy or cholecystectomy should
be performed.
B. Perforation
Perforation may take any of three forms: (1) localized perforation with pericholecystic abscess; (2) free perforation with generalized peritonitis; and (3)
perforation into an adjacent hollow viscus, with the formation of a fistula. Perforation may occur as early as 3 days after the onset of acute cholecystitis
or not until late in the second week. The total incidence of perforation is about 10%.
1. Pericholecystic abscess
Pericholecystic abscess, the most common form of perforation, should be suspected when the signs and symptoms progress, especially when
accompanied by the appearance of a palpable mass. The patient often becomes toxic, with fever to 39°C and a leukocyte count above 15,000/μL, but
sometimes there is no correlation between the clinical signs and the development of local abscess. Cholecystectomy and drainage of the abscess can
be performed safely in many of these patients, but if the patient’s condition is unstable, percutaneous cholecystostomy is preferable.
2. Free perforation
Free perforation occurs in only 1%2% of patients, most often early in the disease when gangrene develops before adhesions wall off the gallbladder.
The diagnosis is made preoperatively in less than half of cases. In some patients with localized pain, sudden spread of pain and tenderness to other
Pericholecystic abscess, the most common form of perforation, should be suspected when the signs and symptoms progress, especially when
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accompanied by the appearance of a palpable mass. The patient often becomes toxic, with fever to 39°C and a leukocyte count above 15,000/μL, but
sometimes there is no correlation between the clinical signs and the development of local abscess. Cholecystectomy and drainage of the abscess can
be performed safely in many of these patients, but if the patient’s condition is unstable, percutaneous cholecystostomy is preferable.
2. Free perforation
Free perforation occurs in only 1%2% of patients, most often early in the disease when gangrene develops before adhesions wall off the gallbladder.
The diagnosis is made preoperatively in less than half of cases. In some patients with localized pain, sudden spread of pain and tenderness to other
parts of the abdomen suggests the diagnosis. Whenever it is suspected, free perforation must be treated by emergency laparotomy. Abdominal
paracentesis may be misleading and has proved to be of little diagnostic usefulness. Cholecystectomy should be performed if the patient’s condition
will permit; otherwise, cholecystostomy is done. The death rate depends partly on whether the cystic duct remains obstructed or the stone becomes
dislodged after perforation. The former leads to a purulent peritonitis that is lethal in 20% of cases. In the latter, a true bile peritonitis ensues and over
50% of patients die. The earlier source control is achieved, the better is the prognosis.
3. Cholecystenteric fistula
If the acutely inflamed gallbladder becomes adherent to adjacent stomach, duodenum, or colon and necrosis develops at the site of one of these
adhesions, perforation may occur into the lumen of the gut. The resulting decompression often allows the acute disease to resolve. If the gallbladder
stones discharge through the fistula and if they are large enough, they may obstruct the small intestine (gallstone ileus; see later section). Rarely,
patients vomit gallstones that have entered the stomach through a cholecystogastric fistula. In most patients, the acute attack subsides and the
cholecystenteric fistula is clinically unsuspected. Fistulas arising from gallstones must be differentiated from those caused by perforated peptic ulcers.
Cholecystenteric fistulas do not usually cause symptoms unless the gallbladder is still partially obstructed by stones or scarring. Malabsorption and
steatorrhea have been reported in isolated cases of cholecystocolonic fistulas. Steatorrhea in this situation could be due either to absence of bile in
the proximal bowel following diversion into the colon or, more rarely, to excess bacteria in the upper intestine. An upper gastrointestinal series or
abdominal CT may delineate the fistula, but often, the fistula will be found intraoperatively.
Treatment
The two mainstays of therapy for acute cholecystitis are antibiotics and biliary decompression (Figure 27–7). Intravenous fluids should be given to
correct dehydration and electrolyte imbalance. Antibiotics directed against enteric gramnegative rods and anaerobes should be given. Single therapy
with piperacillintazobactam or imipenem or dual therapy with ceftriaxone plus metronidazole or ciprofloxacin plus metronidazole are appropriate
options. Choice of antibiotics should account for known patient or regionspecific bacterial resistance patterns.
Figure 27–7.
Schema for the management of acute cholecystitis. CBC, complete blood count; ERCP, endoscopic retrograde cholangiopancreatography; HIDA,
hepatobiliary iminodiacetic acid; LFTs, liver function tests; MRCP, magnetic resonance cholangiopancreatography; PTC, percutaneous transhepatic
cholangiography; RUQ, right upper quadrant; US, ultrasound.
The timing and approach to biliary decompression is dependent upon establishment of the diagnosis, the length of disease at presentation, and the
patient’s preexisting health to undergo surgery. In patients who are reasonablerisk surgical candidates presenting early in their disease course (2472
hours), the preferred method of treatment is laparoscopic cholecystectomy. Four controlled trials have supported this approach with the following
data: (1) the incidence of technical complications is no greater with early surgery; (2) early surgery reduces the total duration of illness by
approximately 30 days, length of hospitalization by 57 days, and direct medical costs by several thousand dollars; and (3) the death rate is slightly
lower with early surgery because of earlier treatment for some patients whose condition would have worsened during expectant management.
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The timing and approach to biliary decompression is dependent upon establishment of the diagnosis, the length of disease at presentation, and the
patient’s preexisting health to undergo surgery. In patients who are reasonablerisk surgical candidates presenting early in their disease course (2472
hours), the preferred method of treatment is laparoscopic cholecystectomy. Four controlled trials have supported this approach with the following
data: (1) the incidence of technical complications is no greater with early surgery; (2) early surgery reduces the total duration of illness by
approximately 30 days, length of hospitalization by 57 days, and direct medical costs by several thousand dollars; and (3) the death rate is slightly
lower with early surgery because of earlier treatment for some patients whose condition would have worsened during expectant management.
In about 30% of cases, the diagnosis of acute cholecystitis is established but the general condition of the patient is unsatisfactory. If possible, surgery
should be postponed in these cases until the ancillary disease is controlled. Percutaneous cholecystostomy can be performed in patients whose
comorbidities preclude surgery. A catheter is inserted under ultrasound or CT guidance to decompress and drain the gallbladder of bile and/or pus.
Along with antibiotics, cholecystostomy controls the acute disease, including any local infection, but the gallstones are not removed. Therefore,
cholecystectomy should be considered to prevent recurrent disease once the patient recovers and attendant comorbidities are optimized.
Alternatively, in nontoxic patients with less severe disease, cholecystitis can be temporized with antibiotics (60% success rate) alone, and an interval
cholecystectomy can be performed after medical optimization. However, failure to promptly improve with antibiotics should lead to consideration of
cholecystostomy or cholecystectomy.
Prognosis
The overall death rate of acute cholecystitis is about 5%. Nearly all of the deaths are in patients over age 60 or those with diabetes mellitus. In the older
age group, secondary cardiovascular or pulmonary complications contribute substantially to the death rate. Uncontrolled sepsis with peritonitis and
intrahepatic abscesses are the most important local conditions responsible for death.
Common duct stones are present in about 15% of patients with acute cholecystitis, and some of the more seriously ill patients have simultaneous
cholangitis from biliary obstruction. Acute pancreatitis may also complicate acute cholecystitis, and the combination carries a greater risk.
Patients who develop the suppurative forms of gallbladder disease such as empyema or perforation are less likely to recover (Figure 27–8). Earlier
admission to the hospital and early cholecystectomy reduce the chances of these complications.
Figure 27–8.
The natural history of gallbladder stones. The numbers approximate the percentage of patients in each category. Note that most patients with acute
cholecystitis have previously had biliary colic.
Gurusamy KS, Rossi M, Davidson BR: Percutaneous cholecystostomy for highrisk surgical patients with acute calculous cholecystitis. Cochrane
Database Syst Rev . 2013;8:CD007088.
Okamoto K, Suzuki K, Takada T, et al: Tokyo Guidelines 2018: flowchart for the management of acute cholecystitis. J Hepatobiliary Pancreat Sci .
2018;25:55–72. [PubMed: 29045062]
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Gurusamy KS, Rossi M, Davidson BR: Percutaneous cholecystostomy for highrisk surgical patients with acute calculous cholecystitis. Cochrane
Database Syst Rev . 2013;8:CD007088.
Okamoto K, Suzuki K, Takada T, et al: Tokyo Guidelines 2018: flowchart for the management of acute cholecystitis. J Hepatobiliary Pancreat Sci .
2018;25:55–72. [PubMed: 29045062]
ACALCULOUS CHOLECYSTITIS
Acute cholecystitis can occur in the absence of cholelithiasis (acalculous cholecystitis). Some of these cases are due to cystic duct obstruction by
another process such as a malignant tumor. More cases of acalculous cholecystitis result from primary bacterial infection by Escherichia coli,
clostridia, or, occasionally, Salmonella typhi. Most cases occur in patients hospitalized with some other critical illness. Diagnosis is usually made after
fever workup in otherwise critical patients reveals evidence for cholecystitis. Due to the nature of patients with this diagnosis, antecedent symptoms of
disease are rare, save for a new fever and leukocytosis.
Acute acalculous cholecystitis is particularly common in trauma victims, in patients receiving total parenteral nutrition, and in patients with other
critical illness. Smallvessel occlusion occurs early, and unless treatment is given promptly, the disease progresses rapidly to gangrenous cholecystitis
and septic complications, at which point the death rate is high. Antibiotics and biliary drainage via percutaneous cholecystostomy are the treatment
modalities of choice.
EMPHYSEMATOUS CHOLECYSTITIS
Emphysematous cholecystitis is a rare condition in which bubbles of gas from anaerobic infection appear in the lumen of the gallbladder, its wall, the
pericholecystic space, and, on occasion, the bile ducts. Clostridia species are the most commonly implicated organisms, but other gasforming
anaerobes such as E coli or anaerobic streptococci may be found. Three times as many men as women are affected, and 20% of patients have diabetes
mellitus. In contrast to the usual form of acute cholecystitis, the disease probably is a bacterial infection from the earliest moment. In many cases, the
gallbladder contains no stones.
The disease begins with sudden and rapidly progressive right upper quadrant pain. Fever and leukocytosis reach high levels quickly, and the patient is
considerably more toxic than is usually the case in acute cholecystitis. On examination, a mass can usually be found in the right upper quadrant.
The patient should be treated with antibiotics effective against clostridia and the other species mentioned earlier. Emergency surgical treatment
should follow the initial resuscitative measures. Cholecystectomy can be safely performed in most cases, but the most critically ill might fare better with
cholecystostomy. The types of complications are the same as in other forms of acute cholecystitis, but illness is more severe and death rates are
higher.
GALLSTONE ILEUS
Gallstone ileus is mechanical intestinal obstruction caused by a large gallstone lodged in the ileal lumen. It occurs more often in women, and the
average patient age is about 70 years.
Clinical Findings
A. Symptoms
The patient usually presents with obvious small bowel obstruction, either partial or complete. The obstructing gallstone enters the intestine through a
cholecystenteric fistula located in the duodenum, colon, or, rarely, the stomach or jejunum. The gallbladder may contain one or several stones, but
stones that cause gallstone ileus are almost always 2.5 cm or more in diameter. The lumen in the proximal bowel will allow most of these large calculi to
pass caudally until the ileum is reached. Obstruction of the large intestine may follow passage of a gallstone through a fistula at the hepatic flexure or
may occur even after the stone has traversed the entire small bowel.
B. Signs
In most patients, the findings on physical examination are typical of distal small bowel obstruction. Obstruction of the duodenum or jejunum may give
a perplexing clinical picture because of the lack of distention. Right upper quadrant tenderness and a mass may be present in some cases, but the
distended abdomen may be difficult to examine accurately.
C. Imaging Studies
In addition to dilated small intestine, abdominal CT scan with oral and intravenous contrast can show air within the biliary tree and a cholecystenteric
B. Signs
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In most patients, the findings on physical examination are typical of distal small bowel obstruction. Obstruction of the duodenum or jejunum may give
a perplexing clinical picture because of the lack of distention. Right upper quadrant tenderness and a mass may be present in some cases, but the
distended abdomen may be difficult to examine accurately.
C. Imaging Studies
In addition to dilated small intestine, abdominal CT scan with oral and intravenous contrast can show air within the biliary tree and a cholecystenteric
fistula.
Treatment
The proper treatment is emergency laparotomy or laparoscopy with removal of the obstructing stone through a small enterotomy. The proximal
intestine must be carefully inspected for the presence of a second calculus that might cause a postoperative recurrence. The gallbladder should be left
undisturbed at the original operation.
Once the patient has recovered, an elective cholecystectomy should be scheduled if the patient complains of chronic gallbladder symptoms. On this
basis, interval cholecystectomy will be required in about 30% of patients. The fistula itself is rarely the source of trouble and closes spontaneously in
most patients.
Prognosis
The death rate from gallstone ileus remains about 20%, largely because of the poor general condition of elderly patients at the time of laparotomy. In
many cases, the patient has developed cardiac or pulmonary complications during a preoperative delay when the diagnosis was unclear.
CHOLEDOCHOLITHIASIS
Biliary pain
Jaundice
Episodic cholangitis
Gallstones in gallbladder or previous cholecystectomy
Approximately 15% of patients with stones in the gallbladder harbor calculi within the bile ducts. Common duct stones are usually accompanied by
others in the gallbladder, but in 5% of cases, the gallbladder is empty. The number of duct stones may vary from 1 to more than 100.
There are two possible origins for common duct stones. The evidence suggests that most cholesterol stones develop within the gallbladder and reach
the duct after traversing the cystic duct. These are called secondary stones. Pigment stones may have a similar pedigree or, more often, develop de
novo within the common duct. These are called primary common duct stones. About 60% of common duct stones are cholesterol stones and 40% are
pigment stones. The latter are, on average, associated with more severe clinical manifestations.
Patients may have one or more of the following principal clinical findings, all of which are caused by obstruction to the flow of bile or pancreatic juice:
biliary colic, cholangitis, jaundice, and pancreatitis (Figure 27–9). It seems, however, that as many as 50% of patients with choledocholithiasis remain
asymptomatic.
Figure 27–9.
The natural history of common duct stones. Of every 100 patients with gallbladder stones, 15 will have common duct stones, which will produce the
spectrum of syndromes illustrated. Note that the individual syndromes overlap, indicating that they may appear together in various combinations.
Figure 27–9. RED de Universidades Anáhuac
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The natural history of common duct stones. Of every 100 patients with gallbladder stones, 15 will have common duct stones, which will produce the
spectrum of syndromes illustrated. Note that the individual syndromes overlap, indicating that they may appear together in various combinations.
The common duct may dilate to 23 cm proximal to an obstructing lesion, and truly huge ducts develop in patients with biliary tumors. In
choledocholithiasis or biliary stricture, the inflammatory reaction restricts dilation, so the dilatation is less marked. Dilation of the ductal system within
the liver can also be limited by cirrhosis.
Biliary colic is the result of rapid rises in biliary pressure whether the block is in the common duct or neck of the gallbladder. Gradual occlusion of the
duct—as in cancer—rarely produces the same kind of pain as gallstone disease.
Clinical Findings
A. Symptoms
Choledocholithiasis may be asymptomatic or may produce sudden toxic cholangitis, leading to a rapid demise. The seriousness of the disease parallels
the degree of obstruction, the length of time it has been present, and the extent of secondary bacterial infection (see later section on cholangitis).
Biliary colic, jaundice, and pancreatitis may be isolated findings or may occur in any combination along with signs of cholangitis.
Biliary colic from common duct obstruction cannot be distinguished from that caused by stones in the gallbladder. The pain is felt in the right
subcostal region, epigastrium, or even the substernal area. Referred pain to the region of the right scapula is common.
Choledocholithiasis should be strongly suspected if intermittent chills, fever, or jaundice accompanies biliary colic. Some patients notice transient
darkening of their urine during an attack even though jaundice is not evident.
Pruritus is usually the result of persistent longstanding obstruction. The itching is more intense in warm weather when the patient perspires and is
usually worse on the extremities than on the trunk. It is much more common with neoplastic obstruction than with gallstone obstruction.
B. Signs
The patient may be icteric and toxic, with high fever and chills, or may appear to be perfectly healthy. A palpable gallbladder is unusual in patients with
obstructive jaundice from common duct stone because the obstruction is transient and partial, and scarring of the gallbladder renders it inelastic and
nondistensible. Tenderness may be present in the right upper quadrant but is not often as marked as in acute cholecystitis, perforated peptic ulcer, or
acute pancreatitis. Tender hepatic enlargement may occur.
C. Laboratory Findings
usually worse on the extremities than on the trunk. It is much more common with neoplastic obstruction than with gallstone obstruction.
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B. Signs
The patient may be icteric and toxic, with high fever and chills, or may appear to be perfectly healthy. A palpable gallbladder is unusual in patients with
obstructive jaundice from common duct stone because the obstruction is transient and partial, and scarring of the gallbladder renders it inelastic and
nondistensible. Tenderness may be present in the right upper quadrant but is not often as marked as in acute cholecystitis, perforated peptic ulcer, or
acute pancreatitis. Tender hepatic enlargement may occur.
In cholangitis, leukocytosis of 15,000/μL is usual, and values above 20,000/μL are common. A rise in serum bilirubin often appears within 24 hours
after the onset of symptoms. The absolute level usually remains under 10 mg/dL, and most levels are in the range of 24 mg/dL. The direct fraction
exceeds the indirect, but the latter becomes elevated in most cases. Bilirubin levels do not ordinarily reach the high values seen in malignant tumors
because the obstruction is usually incomplete and transient.
The serum alkaline phosphatase level usually rises and may be the only chemical abnormality in patients without jaundice. When the obstruction is
relieved, the alkaline phosphatase and bilirubin levels should return to normal within 12 weeks, with the exception that the former may remain
elevated longer if the obstruction was prolonged.
Mild increases in AST and alanine aminotransferase (ALT) are often seen with extrahepatic obstruction of the ducts.
D. Imaging Studies
Ultrasound will usually show gallbladder stones and, depending on the degree of obstruction, dilatation of the bile duct. Ultrasound and CT scans are
insensitive in the search for stones in the common duct. Strong predictors of choledocholithiasis are cholangitis, bilirubin > 4 mg/dL, and a dilated
common bile duct on ultrasound and are indications for ERCP. Intermediate evidence of choledocholithiasis warrants evaluation with intraoperative
cholangiogram or ultrasound or preoperative MRCP. EUS is another sensitive technique for detection of choledocholithiasis and a costeffective
technique to guide subsequent ERCP.
The workup should consider the same possibilities in the differential diagnosis as for cholecystitis.
Elevated serum lipase levels are diagnostic of pancreatitis, which may be the result of choledocholithiasis in the appropriate clinical setting.
Alcoholic cirrhosis or acute alcoholic hepatitis may present with jaundice, right upper quadrant tenderness, and leukocytosis. The differentiation from
cholangitis may be impossible from clinical data. A history of a recent binge suggests acute liver disease. A percutaneous liver biopsy may be specific.
Intrahepatic cholestasis from drugs, pregnancy, chronic active hepatitis, or primary biliary cirrhosis may be difficult to distinguish from extrahepatic
obstruction. MRCP/ERCP would be appropriate to make the distinction, particularly if other studies (eg, ultrasound scan) failed to provide evidence of
gallstone disease. If jaundice has persisted for 46 weeks, a mechanical cause is probable. Because most patients improve during this interval,
persistent jaundice should never be assumed to be the result of parenchymal disease unless imaging rules out obstruction of the major ducts.
Intermittent jaundice and cholangitis after cholecystectomy are compatible with biliary stricture or a retained common bile duct stone, and the
distinction requires MRCP/ERCP.
Biliary tumors usually produce intense jaundice without biliary colic or fever, and once it begins, the jaundice rarely remits.
Complications
Longstanding ductal infection can produce intrahepatic abscesses. Hepatic failure or secondary biliary cirrhosis may develop in unrelieved
obstruction of long duration. Because the obstruction is usually incomplete and intermittent, cirrhosis develops only after several years in untreated
disease. Acute pancreatitis, a fairly common complication of calculous biliary disease, is discussed in Chapter 28. In brief, patients should undergo
supportive care for pancreatitis and undergo cholecystectomy with symptomatic improvement on the indexed operation. There is a nearly 25%
recurrence of gallstone pancreatitis treated without cholecystectomy within the following 3 months.
Rarely, a stone in the common duct may erode through the ampulla, resulting in gallstone ileus. Hemorrhage (hemobilia) is also a rare complication.
Treatment
Patients with acute cholangitis should be treated with systemic antibiotics and other measures, as described in the following section, followed by
urgent or emergent, depending on the patient’s condition, decompression of the bile duct through either endoscopic sphincterotomy or surgical
common bile duct exploration.
disease. Acute pancreatitis, a fairly common complication of calculous biliary disease, is discussed in Chapter 28. In brief, patients should undergo
supportive care for pancreatitis and undergo cholecystectomy with symptomatic improvement on the indexed operation. There is a nearly 25%
recurrence of gallstone pancreatitis treated without cholecystectomy within the following 3 months. Access Provided by:
Rarely, a stone in the common duct may erode through the ampulla, resulting in gallstone ileus. Hemorrhage (hemobilia) is also a rare complication.
Treatment
Patients with acute cholangitis should be treated with systemic antibiotics and other measures, as described in the following section, followed by
urgent or emergent, depending on the patient’s condition, decompression of the bile duct through either endoscopic sphincterotomy or surgical
common bile duct exploration.
The typical patient presents with mild cholangitis and evidence on ultrasound scans of gallbladder stones. Laparoscopic cholecystectomy is indicated
along with, depending on the experience of the surgeon, laparoscopic exploration of the common duct if an operative cholangiogram or laparoscopic
ultrasound demonstrates the expected common duct stones. Laparoscopic common duct exploration is usually accomplished through the cystic duct
(which may have to be dilated), but when the common duct is enlarged (> 1.5 cm), it may be accomplished through a choledochotomy incision, just as
in open surgery. If the surgeon thinks the common duct stones cannot be removed laparoscopically, it is probably best to remove the gallbladder
laparoscopically and the common duct stones by endoscopic sphincterotomy. If the stones cannot be removed by sphincterotomy, a second (open)
operation may be necessary. To avoid the need for a second operation, ERCP to remove common duct stones may be considered prior to proceeding
to the operating room for cholecystectomy.
There is also a lack of consensus regarding the importance of operative cholangiography or ultrasound during cholecystectomy when there are no
clues suggesting stones in the duct. In such cases, the chances of finding a stone are only 3%5%, and because many of these stones will pass
spontaneously without clinical sequelae, some consider the effort unwarranted. However, operative cholangiograms also provide confirmation of the
biliary anatomy, which contributes to avoidance of bile duct injuries and allows prompt treatment of those stones that would go on to cause
symptoms.
When the common duct is explored through the cystic duct and gallstones are removed, the cystic duct must be ligated, but a drainage catheter is not
usually left within the common duct. When the common duct is explored through a choledochotomy (either during a laparoscopic or open operation),
a T tube is usually left in the duct, and cholangiograms are taken a week or so postoperatively. Any residual stones discovered on these postoperative
xrays can be extracted 46 weeks later through the T tube tract.
Patients with common duct stones who have had a previous cholecystectomy are best treated by endoscopic sphincterotomy. Using a sideviewing
duodenoscope, the ampulla is cannulated, and a 1cm incision is made in the sphincter with an electrocautery wire. The opening created in the
sphincter permits stones to pass from the duct into the duodenum. Endoscopic sphincterotomy is less likely to be successful in patients with large
stones (eg, > 2 cm), and it is contraindicated in the presence of stenosis of the bile duct proximal to the sphincter. In these cases, common duct
exploration is required.
Stones in the intrahepatic branches of the bile duct can usually be removed without difficulty during common duct exploration. In some cases,
however, one or more of the intrahepatic ducts have become packed with stones, and the associated chronic inflammation has produced stenosis of
the duct near its junction with the common hepatic duct. It is often impossible in these cases to clear the duct of stones, and if the disease involves only
one lobe (usually the left lobe), hepatic lobectomy is indicated.
ASGE Standards of Practice Committee: The role of endoscopy in the evaluation of suspected choledocholithiasis. Gastrointest Endosc . 2010;71:1–9.
[PubMed: 20105473]
CHOLANGITIS (BACTERIAL CHOLANGITIS)
Bacterial infection of the biliary ducts always signifies biliary obstruction because, in the absence of obstruction, even heavy bacterial contamination of
the ducts fails to produce symptoms or pathologic changes. The block to flow may be partial or, less commonly, complete. The principal causes are
choledocholithiasis, biliary stricture, and neoplasm. Less common causes are chronic pancreatitis, ampullary stenosis, pancreatic pseudocyst,
duodenal diverticulum, congenital cyst, and parasitic invasion. Iatrogenic cholangitis may complicate transhepatic or T tube cholangiography. Not all
obstructing lesions are followed by cholangitis, however. For example, biliary infection develops in only 15% of patients with neoplastic obstruction.
The likelihood of cholangitis is greatest when the obstruction occurs after the duct has acquired a resident bacterial population.
With obstruction, ductal pressure rises, and bacteria proliferate and escape into the systemic circulation via the hepatic sinusoids. Experimentally, the
incidence of positive blood cultures with ductal infection is directly proportionate to the absolute height of the pressure in the duct.
The symptoms of cholangitis (sometimes referred to as the Charcot triad) are biliary colic, jaundice, and chills and fever, although a complete triad is
present in only 70% of cases. Laboratory findings include leukocytosis and elevated serum bilirubin and alkaline phosphatase levels. The predominant
organisms in bile (in approximately decreasing frequency) are E coli, Klebsiella, Pseudomonas, enterococci, and Proteus. Bacteroides fragilis and other
anaerobes (eg, Clostridium perfringens) can be detected in about 25% of cases, and their presence correlates with multiple previous biliary operations
duodenal diverticulum, congenital cyst, and parasitic invasion. Iatrogenic cholangitis may complicate transhepatic or T tube cholangiography. Not all
obstructing lesions are followed by cholangitis, however. For example, biliary infection develops in only 15% of patients with neoplastic obstruction.
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The likelihood of cholangitis is greatest when the obstruction occurs after the duct has acquired a resident bacterial population.
With obstruction, ductal pressure rises, and bacteria proliferate and escape into the systemic circulation via the hepatic sinusoids. Experimentally, the
incidence of positive blood cultures with ductal infection is directly proportionate to the absolute height of the pressure in the duct.
The symptoms of cholangitis (sometimes referred to as the Charcot triad) are biliary colic, jaundice, and chills and fever, although a complete triad is
present in only 70% of cases. Laboratory findings include leukocytosis and elevated serum bilirubin and alkaline phosphatase levels. The predominant
organisms in bile (in approximately decreasing frequency) are E coli, Klebsiella, Pseudomonas, enterococci, and Proteus. Bacteroides fragilis and other
anaerobes (eg, Clostridium perfringens) can be detected in about 25% of cases, and their presence correlates with multiple previous biliary operations
(often including a biliary enteric anastomosis), severe symptoms, and a high incidence of postoperative suppurative complications. Anaerobes are
nearly always seen in the company of aerobes. Two species of bacteria can be cultured in about 50% of cases. Bacteremia probably occurs in most
cases, and blood cultures obtained at the appropriate time contain the same organisms as the bile. An ultrasound will often give useful diagnostic
information suggestive of biliary obstruction.
The term suppurative cholangitis has been used for the most severe form of this disease, when manifestations of sepsis overshadow those of
hepatobiliary disease. The diagnostic pentad of suppurative cholangitis consists of abdominal pain, jaundice, fever and chills, mental confusion or
lethargy, and shock. The diagnosis is often missed because the signs of biliary disease are overlooked.
Most cases of cholangitis can be controlled with intravenous antibiotics, as stated earlier, followed by prompt ERCP with sphincterotomy and bile duct
decompression. In the uncommon case where this is unsuccessful, laparotomy is indicated in order to decompress the bile duct through a formal
common bile duct exploration or, in the most extreme instances, direct common bile duct decompression. Cholangitis accompanying neoplastic
obstruction may be managed by insertion of a transhepatic drainage catheter into the bile duct.
Miura F, Okamoto K, Takada T, et al: Tokyo Guidelines 2018: initial management of acute biliary infection and flowchart for acute cholangitis. J
Hepatobiliary Pancreat Sci . 2018;25:31–40. [PubMed: 28941329]
POSTCHOLECYSTECTOMY SYNDROME
The term postcholecystectomy syndrome has been used to signify the heterogeneous group of disorders affecting patients who continue to complain
of symptoms after cholecystectomy. It is not really a syndrome, and the term is confusing.
The usual reason for incomplete relief after cholecystectomy is that the preoperative diagnosis of chronic cholecystitis was incorrect. The only
symptom entirely characteristic of chronic cholecystitis is biliary colic. When a calculous gallbladder is removed in the hope that the patient will gain
relief from dyspepsia, fatty food intolerance, belching, and other symptoms, the operation may leave the symptoms unchanged.
The presenting symptom may be dyspepsia or pain. An organic cause for the symptoms is more likely to be discovered in patients with severe episodic
pain than in those with other complaints. Abnormal liver function studies, jaundice, and cholangitis are other manifestations that indicate residual
biliary disease. Patients with suspicious findings should be studied by MRCP, ERCP, or THC. Choledocholithiasis, biliary stricture, and chronic
pancreatitis are the most common causes of symptoms. Occasionally, there is sufficient evidence to implicate sphincter of Oddi dysmotility as a cause
of pain. Relief of pain may follow endoscopic sphincterotomy. Stenosis of the hepatobiliary ampulla, a long cystic duct remnant, and neuromas have
been blamed for continued symptoms.
CARCINOMA OF THE GALLBLADDER
Carcinoma of the gallbladder is an uncommon neoplasm that occurs in elderly patients. It is associated with gallstones in 70% of cases, and the risk of
malignant degeneration correlates with the length of time gallstones have been present. The tumor is twice as common in women as in men, as one
would expect from the association with gallstones.
Most primary tumors of the gallbladder are adenocarcinomas that appear histologically to be scirrhous (60%), papillary (25%), or mucoid (15%).
Dissemination of the tumor occurs early by direct invasion of the liver and hilar structures and by metastases to the common duct lymph nodes, liver,
and lungs. In an occasional case, where carcinoma is an incidental finding after cholecystectomy for gallstone disease, the tumor is confined to the
gallbladder as a carcinoma in situ or an early invasive lesion. Most invasive carcinomas, however, have spread by the time of surgery, and spread is
virtually certain if the tumor has progressed to the point where it causes symptoms.
Clinical Findings
The most common presenting complaint is of right upper quadrant pain similar to previous episodes of biliary colic but more persistent. Obstruction
Dissemination of the tumor occurs early by direct invasion of the liver and hilar structures and by metastases to the common duct lymph nodes, liver,
and lungs. In an occasional case, where carcinoma is an incidental finding after cholecystectomy for gallstone disease, the tumor is confined to the
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gallbladder as a carcinoma in situ or an early invasive lesion. Most invasive carcinomas, however, have spread by the time of surgery, and spread is
virtually certain if the tumor has progressed to the point where it causes symptoms.
Clinical Findings
The most common presenting complaint is of right upper quadrant pain similar to previous episodes of biliary colic but more persistent. Obstruction
of the cystic duct by tumor sometimes initiates an attack of acute cholecystitis. Other cases present with obstructive jaundice and, occasionally,
cholangitis due to secondary involvement of the common duct.
Examination usually reveals a mass in the region of the gallbladder, which may not be recognized as a neoplasm if the patient has acute cholecystitis. If
cholangitis is the principal symptom, a palpable gallbladder would be an unusual finding with choledocholithiasis alone and should suggest
gallbladder carcinoma.
B. Imaging Studies
CT and ultrasound scans may demonstrate the extent of disease, but more often, they show only gallstones. The correct diagnosis is made
preoperatively in only 10% of cases.
Complications
Obstruction of the common duct may produce multiple intrahepatic abscesses. Abscesses in or next to the tumorladen gallbladder are frequent.
Prevention
The incidence of gallbladder cancer has decreased in recent years as the frequency of cholecystectomy has increased. It has been estimated that one
case of gallbladder cancer is prevented for every 100 cholecystectomies performed for gallstone disease.
Treatment
If a localized carcinoma of the gallbladder is recognized at laparotomy, cholecystectomy should be performed along with en bloc wedge resection of an
adjacent 35 cm of normal liver and dissection of the lymph nodes in the hepatoduodenal ligament. If a small invasive carcinoma overlooked during
cholecystectomy for gallstone disease is later discovered by the pathologist, reoperation is indicated to perform a wedge resection of the liver bed plus
regional lymphadenectomy. Some surgeons also recommend that the common duct be included routinely (ie, even in the absence of gross invasion) in
the lymph node dissection for any lesion that involves the full thickness of the gallbladder wall. In the few cases when cancer has not penetrated the
muscularis mucosae, cholecystectomy alone should suffice. More extensive hepatectomies (eg, right lobectomy) are not worthwhile. Lesions that
invade the bile duct and produce jaundice should be resected if possible. When not possible, a stent should be inserted endoscopically or
percutaneously. There is little that surgery can offer in cases with hepatic metastases or more distant spread.
Prognosis
Radiotherapy and chemotherapy are not effective palliative measures. About 85% of patients are dead within a year after diagnosis.
The 10% of patients who presently survive more than 5 years consist of those whose carcinoma was an incidental finding during cholecystectomy for
symptomatic gallstone disease and those in whom an aggressive resection has removed all gross tumor.
Mayo SC, Shore AD, Nathan H, et al: National trends in the management and survival of surgically managed gallbladder adenocarcinoma over 15
years: a populationbased analysis. J Gastrointest Surg . 2010;14(10):1578–1591. [PubMed: 20824371]
Wu LM, Jiang XX, Gu HY, et al: Endoscopic ultrasoundguided fineneedle aspiration biopsy in the evaluation of bile duct strictures and gallbladder
masses: a systematic review and metaanalysis. Eur J Gastroenterol Hepatol . 2011;23(2):113–120. [PubMed: 21183858]
MALIGNANT TUMORS OF THE BILE DUCT
Intense cholestatic jaundice and pruritus
Anorexia and dull right upper quadrant pain
masses: a systematic review and metaanalysis. Eur J Gastroenterol Hepatol . 2011;23(2):113–120. [PubMed: 21183858]
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MALIGNANT TUMORS OF THE BILE DUCT
Intense cholestatic jaundice and pruritus
Anorexia and dull right upper quadrant pain
Dilated intrahepatic bile ducts on ultrasound or CT scan
Focal stricture on transhepatic or retrograde endoscopic cholangiogram
Primary bile duct tumors are not more common in patients with cholelithiasis, and men and women are affected with equal frequency. Tumors appear
at an average age of 60 years. Ulcerative colitis is a common associated condition, and in occasional cases, bile duct cancer develops in a patient with
ulcerative colitis who has been known to have sclerosing cholangitis for several years. Chronic parasitic infestation of the bile ducts may be
responsible for the greater incidence of bile duct tumors in Asia.
Most malignant biliary tumors are adenocarcinomas located in the hepatic or common bile duct. The histologic pattern varies from typical
adenocarcinoma to tumors composed principally of fibrous stroma and few cells. The acellular tumors may be mistaken for benign strictures or
sclerosing cholangitis if adequate biopsies are not obtained. About 10% are bulky papillary tumors, which tend to be less invasive and less apt to
metastasize.
At presentation, metastases are uncommon, but the tumor has often grown into the portal vein or hepatic artery.
Clinical Findings
The illness presents with gradual onset of jaundice or pruritus. Chills, fever, and biliary colic are usually absent, and except for a deep discomfort in the
right upper quadrant, the patient feels well. Bilirubinuria is present from the start, and lightcolored stools are usual. Anorexia and weight loss develop
insidiously with time.
Icterus is the most obvious physical finding. If the tumor is located in the common duct, the gallbladder may distend and become palpable in the right
upper quadrant. The tumor itself is never palpable. Patients with tumors of the hepatic duct do not develop palpable gallbladders. Hepatomegaly is
common. If obstruction is unrelieved, the liver may eventually become cirrhotic, and splenomegaly, ascites, or bleeding varices become secondary
manifestations.
Because the duct is often completely obstructed, the serum bilirubin is usually over 15 mg/dL. Serum alkaline phosphatase is also increased. Fever and
leukocytosis are not common, because the bile is sterile in most cases. The stool may contain occult blood, but this is more common with tumors of the
pancreas or hepatopancreatic ampulla than those of the bile ducts.
C. Imaging Studies
Ultrasound or CT scans usually detect dilated intrahepatic bile ducts. MRCP, ERCP with EUS, or THC clearly depicts the lesion. THC better demonstrates
the ductal anatomy on the hepatic side of the lesion. With tumors involving the bifurcation of the common hepatic duct (Klatskin tumors), it is
important to determine the proximal extent of the lesion (ie, whether the first branches of the lobar ducts are also involved). ERCP is of value with
proximal tumors because if it shows concomitant obstruction of the cystic duct, the diagnosis will most often prove to be gallbladder cancer invading
the common duct (not a primary common duct neoplasm). The typical pattern with distal bile duct cancers consists of stenosis of the bile duct with
sparing of the pancreatic duct. Adjacent stenoses of both ducts (the doubleduct sign) indicate primary cancer of the pancreas. MRCP may be useful if
highquality studies are available.
Occasionally, bile samples obtained at the time of THC will show malignant cells on cytologic study, but this is not a particularly useful test since the
diagnosis of cancer must be presumed from the cholangiographic findings and a negative cytologic study is unreliable. Angiography may suggest
invasion of the portal vein or encasement of the hepatic artery. False positives may occur, however.
the ductal anatomy on the hepatic side of the lesion. With tumors involving the bifurcation of the common hepatic duct (Klatskin tumors), it is
important to determine the proximal extent of the lesion (ie, whether the first branches of the lobar ducts are also involved). ERCP is of value with
proximal tumors because if it shows concomitant obstruction of the cystic duct, the diagnosis will most often prove to be gallbladder cancer invading
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the common duct (not a primary common duct neoplasm). The typical pattern with distal bile duct cancers consists of stenosis of the bile duct with
sparing of the pancreatic duct. Adjacent stenoses of both ducts (the doubleduct sign) indicate primary cancer of the pancreas. MRCP may be useful if
highquality studies are available.
Occasionally, bile samples obtained at the time of THC will show malignant cells on cytologic study, but this is not a particularly useful test since the
diagnosis of cancer must be presumed from the cholangiographic findings and a negative cytologic study is unreliable. Angiography may suggest
invasion of the portal vein or encasement of the hepatic artery. False positives may occur, however.
The differential diagnosis must consider other causes of extrahepatic and intrahepatic cholestatic jaundice. Choledocholithiasis is characterized by
episodes of partial obstruction, pain, and cholangitis, which contrast with the unremitting jaundice of malignant obstruction. Bilirubin concentrations
rarely surpass 15 mg/dL and are usually below 10 mg/dL in gallstone obstruction, whereas bilirubin levels almost always exceed 10 mg/dL and are
usually above 15 mg/dL in neoplastic obstruction. A rapid rise of the bilirubin level to above 15 mg/dL in a patient with sclerosing cholangitis should
suggest superimposed neoplasm. Dilatation of the gallbladder may occur with tumors of the distal common duct but is rare with calculous obstruction.
The combination of an enlarged gallbladder with painless, obstructive jaundice is usually recognized as being due to tumor. If the gallbladder cannot
be felt, primary biliary cirrhosis, druginduced jaundice, chronic active hepatitis, metastatic hepatic cancer, and common duct stone must be ruled out.
In general, any patient with cholestatic jaundice of more than 2 weeks in duration whose diagnosis is uncertain should be studied by THC or ERCP. The
finding of focal bile duct stenosis in the absence of previous biliary surgery is almost pathognomonic of neoplasm.
Treatment
Patients without evidence of metastases or other signs of advanced cancer (eg, ascites) are candidates for laparotomy. The 30% of patients who do not
qualify may be treated by insertion of a stent into the bile duct transhepatically under radiologic control or from the duodenum under endoscopic
control. The tube is positioned so that holes above and below the tumor reestablish flow of bile into the duodenum. If both lobar ducts are blocked by
a tumor at the bifurcation of the common hepatic duct, it is usually necessary to place a transhepatic tube into only one lobar duct. If the lesion blocks
the takeoff of the segmental ducts, stents are rarely beneficial.
Laparotomy is indicated in most cases, however, with the objective of removing the tumor. Preoperative decompression of the bile duct with a
percutaneous catheter to relieve jaundice does not lower the incidence of postoperative complications. At operation, which may be immediately
preceded by diagnostic laparoscopy, the extent of the tumor should be determined by external examination of the bile duct and the adjacent portal
vein and hepatic artery.
Tumors of the distal common duct should be treated by radical pancreaticoduodenectomy if it appears that all tumor would be removed. Secondary
involvement of the portal vein is the usual reason for unresectability of tumors in this location. Mid common duct or low hepatic duct tumors should
also be removed if possible. If the tumor cannot be excised, bile flow should be reestablished into the intestine by a cholecystojejunostomy or Roux
enY choledochojejunostomy. The choice is based on technical considerations.
Tumors at the hilum of the liver should be resected if possible and a RouxenY hepaticojejunostomy performed. The anastomosis is usually between
hilum and bowel rather than between individual bile ducts and bowel. A curative operation nearly always requires resection of either the right or the
left lobe of the liver and, in all cases, the caudate lobe. Extension into the lobar and segmental ducts and secondary involvement of the hepatic artery
and portal vein are the most common reasons for inability to resect the tumor. Subtotal resections offer little in the way of palliation.
Postoperative radiotherapy is commonly recommended.
Prognosis
The average patient with adenocarcinoma of the bile duct survives less than a year. The overall 5year survival rate is 15%. Following a thorough radical
operation, 5year survival is about 40%. Biliary cirrhosis, intrahepatic infection, and general debility with terminal pneumonitis are the usual causes of
death. Palliative resections and stents may improve the length and quality of survival in this disease even though surgical cure is uncommon. Limited
experience with liver transplantation for this disease has been discouraging: tumor has recurred postoperatively in most patients.
American Society for Gastrointestinal Endoscopy (ASGE) Standards of Practice Committee: The role of endoscopy in the evaluation and treatment of
patients with biliary neoplasia. Gastrointest Endosc . 2013;77(2):167–174. [PubMed: 23219047]
Chapter 27: Biliary Tract, David A. Harris; Eric G. Sheu
National Comprehensive Cancer Network: NCCN guidelines Version 3.2018 Hepatobiliary Cancers.
Page 26 / 32
https://www.nccn.org/professionals/physician_gls/default.aspx
operation, 5year survival is about 40%. Biliary cirrhosis, intrahepatic infection, and general debility with terminal pneumonitis are the usual causes of
death. Palliative resections and stents may improve the length and quality of survival in this disease even though surgical cure is uncommon. Limited
experience with liver transplantation for this disease has been discouraging: tumor has recurred postoperatively in most patients.
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American Society for Gastrointestinal Endoscopy (ASGE) Standards of Practice Committee: The role of endoscopy in the evaluation and treatment of
patients with biliary neoplasia. Gastrointest Endosc . 2013;77(2):167–174. [PubMed: 23219047]
National Comprehensive Cancer Network: NCCN guidelines Version 3.2018 Hepatobiliary Cancers.
https://www.nccn.org/professionals/physician_gls/default.aspx
BENIGN TUMORS & PSEUDOTUMORS OF THE GALLBLADDER
Various unrelated lesions appear on ultrasound as projections from the gallbladder wall. The differentiation from gallstones is based on observing
whether a shift in position of the projections follows changes in posture of the patient, since stones are not fixed. Cancer should be suspected in any
polypoid lesion that exceeds 1 cm in diameter.
Polyps
Most of these are not true neoplasms but cholesterol polyps, a local form of cholesterolosis. Histologically, they consist of a cluster of lipidfilled
macrophages in the submucosa. They easily become detached from the wall when the gallbladder is handled at surgery. It is not known whether
cholesterol polyps are important in the genesis of gallstones. Some patients experience gallbladder pain, but whether this is related to the presence of
the polyps per se or is a manifestation of functional gallbladder disease has not been established.
Inflammatory polyps have also been reported, but they are quite rare.
Adenomyomatosis
On cholecystography, this entity presents as a slight intraluminal convexity that is often marked by central umbilication. It is usually found in the
fundus but may occur elsewhere. It is unclear whether adenomyomatosis is an acquired degenerative lesion or a developmental abnormality (ie,
hamartoma). The following synonyms for this lesion appear in the literature: adenomatous hyperplasia, cholecystitis glandularis proliferans, and
diverticulosis of the gallbladder. Although the condition is probably asymptomatic in many cases, adenomyomatosis can cause abdominal pain.
Cholecystectomy should be performed in such patients.
Adenomas
These appear as pedunculated adenomatous polyps, true neoplasms that may be papillary or nonpapillary histologically. In a few cases, they have
been found in association with carcinoma in situ of the gallbladder.
Treatment of Polyps
In patients with polyps with coincident gallstones or symptoms of biliary colic, cholecystectomy is recommended. Not uncommonly, pathology will
reveal gallstones rather than polyps. In those with polyps that are asymptomatic, cholecystectomy is recommended for polyps > 1 cm in size or with
concerning radiologic features, given the possible association with gallbladder cancer. Serial ultrasounds are recommended for smaller polyps;
enlargement and development of concerning radiologic features are indications for cholecystectomy.
BENIGN TUMORS OF THE BILE DUCTS
Benign papillomas and adenomas may arise from the ductal epithelium. Only 90 cases have been reported to date. The neoplastic propensity of the
ductal epithelium is widespread, so the tumors are often multiple, and recurrence is common after excision. The affected duct must be radically
excised for permanent cure to result.
BILE DUCT INJURIES, BILE LEAK, STRICTURES, & RETAINED STONES
Previous biliary surgery
HIDA scans, ERCP, MRCP, and THC can aid in the diagnosis
ductal epithelium is widespread, so the tumors are often multiple, and recurrence is common after excision. The affected duct must be radically
excised for permanent cure to result.
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BILE DUCT INJURIES, BILE LEAK, STRICTURES, & RETAINED STONES
Previous biliary surgery
HIDA scans, ERCP, MRCP, and THC can aid in the diagnosis
Benign biliary injuries and strictures are caused by surgical trauma in about 95% of cases. The remainder result from external abdominal trauma or,
rarely, from erosion of the duct by a gallstone. Prevention of injury to the duct depends on a combination of technical skill, experience, and a thorough
knowledge of the normal anatomy and its variations in the hilum of the liver. The number of bile duct injuries rose sharply with the advent of
laparoscopy; however, with the increased experience with this technique, bile duct injury rates have improved
The most common lesion consists of excision of a segment of the common duct as a result of mistaking it for the cystic duct. Partial transection,
occlusion with metal clips, injury to the right hepatic duct, and leakage from the cystic duct are other examples. A full discussion of how these injuries
occur and how they can be prevented is beyond the scope of this text. However, as described earlier, identification of the critical view of safety has been
advocated as a method to reduce the incidence of bile duct injury in laparoscopic cholecystectomy.
Clinical Findings
A. Symptoms
Manifestations of postoperative complications are variable. Patients with a retained stone, bile duct injury, or leak often present within days to weeks
of their index operation with recurrent right upper quadrant pain. In the case of biliary leak, biliary ascites leads to abdominal distention, bloating,
pain, and mild jaundice. Retained common bile duct stones typically result in biliary colic–type pain. Jaundice may accompany both retained bile duct
stones and bile duct stricture.
B. Signs
Findings are not distinctive. Bile ascites produces abdominal distention and ileus and, rarely, true bile peritonitis with toxicity. The right upper
quadrant may be tender but usually is not. Jaundice is usually present during an attack of choledocholithiasis or cholangitis.
The serum alkaline phosphatase and bilirubin concentration are often elevated in cases of stricture or retained bile duct stones. Leukocytosis is often
present in patients with biliary ascites.
D. Imaging Studies
Bile ascites can be suspected on ultrasound or CT scan. The fluid should be aspirated, and if it is bile, the diagnosis is clear. Alternatively, a HIDA scan
can be used to identify a biliary leak. ERCP can identify the leak and its location and also allow treatment of leaks from the cystic duct or ducts of
Luschka by placement of a common bile duct stent.
After laparoscopic cholecystectomy, the most common pattern of iatrogenic stricture is from focal narrowing of the common hepatic duct within 2 cm
of the bifurcation and mild to moderate dilatation of the intrahepatic ducts.
Choledocholithiasis is the condition that most often must be differentiated from biliary stricture because the clinical and laboratory findings can be
identical. A history of trauma to the duct would point toward stricture as the more likely diagnosis. Other causes of cholestatic jaundice may have to be
ruled out in some cases.
Complications
Complications develop quickly if the leak is not controlled. Bile peritonitis and abscesses may form. With stricture, persistent cholangitis may progress
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Choledocholithiasis is the condition that most often must be differentiated from biliary stricture because the clinical and laboratory findings can be
identical. A history of trauma to the duct would point toward stricture as the more likely diagnosis. Other causes of cholestatic jaundice may have to be
ruled out in some cases.
Complications
Complications develop quickly if the leak is not controlled. Bile peritonitis and abscesses may form. With stricture, persistent cholangitis may progress
to multiple intrahepatic abscesses and a septic death.
Treatment
Bile leak from a cystic duct stump, liver edge, or duct of Luschka can often be managed via ERCP with biliary stenting. Surgical exploration with direct
ligation of the leak and drainage is also an option.
Bile duct strictures should be surgically repaired in all but a few patients who are likely to improve with a nonoperative approach. Depending on the
injury pattern, ERCP with stenting may be a therapeutic option, but excision of the damaged duct and RouxenY hepaticojejunostomy are ultimately
indicated for most acute and chronic injuries. The entire biliary tree must be outlined by cholangiograms preoperatively. The key to success is the
thoroughness of the dissection and the ability ultimately to suture healthy duct to healthy bowel. This, in turn, depends on the experience of the
surgeon with this particular operation.
When a definitive repair is technically impossible, the stricture may be dilated with a transhepatic balloontipped catheter. This is particularly
applicable to patients with portal hypertension, whose hepatic hilum contains numerous venous collaterals that make operation hazardous.
Prognosis
The death rate from biliary injuries is about 5%, and severe illness is frequent. If the stricture is not repaired, episodic cholangitis and secondary liver
disease are inevitable.
Surgical correction of the stricture should be successful in about 90% of cases. Experience at centers with a special interest in this problem indicates
that good results can be obtained even if several previous attempts did not relieve the obstruction. There is essentially no place for liver
transplantation in this disease.
Strasberg SM: A teaching program for the “culture of safety in cholecystectomy” and avoidance of bile duct injury. J Am Coll Surg . 2013;217(4):751.
[PubMed: 23707046]
UNCOMMON CAUSES OF BILE DUCT OBSTRUCTION
Congenital Choledochal Cysts
About 30% of congenital choledochal cysts produce their first symptoms in adults, usually presenting with jaundice, cholangitis, and a right upper
quadrant mass. Diagnosis can be made by THC or ERCP. The optimal surgical procedure is excision of the cyst and construction of a RouxenY
hepaticojejunostomy. If this is not technically possible or if the patient’s condition will not permit a prolonged operation, the cyst should be emptied of
precipitated biliary sludge and a cystenteric anastomosis constructed. Congenital cysts of the biliary tree have a high incidence of malignant
degeneration, which is another argument for excision rather than drainage.
Caroli Disease
Caroli disease, another form of congenital cystic disease, consists of saccular intrahepatic dilatation of the ducts. In some cases, the biliary abnormality
is an isolated finding, but more often, it is associated with congenital hepatic fibrosis and medullary sponge kidney. The latter patients often present in
childhood or as young adults with complications of portal hypertension. Others have cholangitis and obstructive jaundice as initial manifestations.
There is no definitive surgical solution to the problem except in rare cases with isolated involvement of one hepatic lobe, where lobectomy is curative.
Intermittent antibiotic therapy for cholangitis is the usual regimen.
Hemobilia
Hemobilia presents with the triad of biliary colic, obstructive jaundice, and occult or gross intestinal bleeding. Most cases in Western cultures follow
several weeks after hepatic trauma with bleeding from an intrahepatic branch of the hepatic artery into a duct. It is seen with less frequency now
because the general principles of management of hepatic trauma are better understood. Hemobilia can also follow ductal parasitism (Ascaris
is an isolated finding, but more often, it is associated with congenital hepatic fibrosis and medullary sponge kidney. The latter patients often present in
childhood or as young adults with complications of portal hypertension. Others have cholangitis and obstructive jaundice as initial manifestations.
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There is no definitive surgical solution to the problem except in rare cases with isolated involvement of one hepatic lobe, where lobectomy is curative.
Intermittent antibiotic therapy for cholangitis is the usual regimen.
Hemobilia
Hemobilia presents with the triad of biliary colic, obstructive jaundice, and occult or gross intestinal bleeding. Most cases in Western cultures follow
several weeks after hepatic trauma with bleeding from an intrahepatic branch of the hepatic artery into a duct. It is seen with less frequency now
because the general principles of management of hepatic trauma are better understood. Hemobilia can also follow ductal parasitism (Ascaris
lumbricoides) or cholangiohepatitis. Other causes are hepatic neoplasms, rupture of a hepatic artery aneurysm, hepatic abscess, and
choledocholithiasis. The diagnosis may be suspected from a CT angiogram or technetium99m–labeled red blood cell scan. Sometimes the bleeding
can be stopped by embolizing the lesion with stainless steel coils, Gelfoam, or autologous blood clot infused through a catheter selectively positioned
in the hepatic artery. If this is unsuccessful, either direct ligation of the bleeding point in the liver or proximal ligation of an upstream branch of the
hepatic artery in the hilum is required.
Pancreatitis
Pancreatitis can cause obstruction of the intrapancreatic portion of the bile duct by inflammatory swelling, encasement with scar, or compression by a
pseudocyst. The patient may present with painless jaundice or cholangitis. Occasionally, a distended gallbladder can be felt on abdominal
examination. Differentiation from choledocholithiasis and secondary acute pancreatitis depends on biliary imaging and evaluation. Jaundice due to
inflammation alone rarely lasts more than 2 weeks; persistent jaundice following an attack of acute pancreatitis suggests the development of a
pseudocyst, underlying chronic pancreatitis with obstruction by fibrosis, or even an obstructing neoplasm.
Biliary obstruction from chronic pancreatitis may have few or no clinical manifestations. Jaundice is usually present, but the average peak bilirubin
level is only 45 mg/dL. Some patients with functionally significant stenosis have persistently elevated alkaline phosphatase levels as the only
abnormality; when surgical decompression of the bile duct is not performed, these patients often develop secondary biliary cirrhosis within a year or
so. Diagnosis of stricture is made by MRCP or ERCP, which shows a long stenosis of the intrapancreatic portion of the duct, proximal dilatation, and
either a gradual or abrupt tapering of the lumen at the pancreatic border, occasionally accompanied by ductal angulation. If cholangiograms show
stenosis and if alkaline phosphatase or bilirubin levels remain more than twice normal for longer than 2 months, the stenosis is functionally significant
and unlikely to resolve and requires surgical correction. Choledochoduodenostomy is done in most cases. Cholecystoduodenostomy is unreliable
because the cystic duct is often too narrow to provide continued biliary decompression.
Patients with obstructive jaundice and pseudocyst usually respond to endoscopic or surgical drainage of the pseudocyst. However, occasionally they
do not respond, because chronic scarring—not the cyst—is the cause of obstruction. Procedures to drain both the bile duct and the pseudocyst are
indicated if there is persistent bile duct obstruction after the cyst has been decompressed.
Ampullary Dysfunction & Stenosis
Stenosis of the hepatopancreatic ampulla (ampullary stenosis) has been implicated as a cause of pain and other manifestations of ampullary
obstruction and is often considered as a cause of postcholecystectomy complaints. Some cases are idiopathic, whereas others may be the result of
trauma from gallstones. If the patient has secondary manifestations of biliary obstruction (eg, jaundice, increased alkaline phosphatase concentration,
cholangitis) in the absence of gallstones or some other obstructing lesion and cholangiography shows dilatation of the common duct, ampullary
stenosis is a plausible explanation. However, the diagnosis is more often proposed as a reason for upper abdominal pain without these more objective
findings. Ampullary dysfunction is postulated in these cases.
Sphincter of Oddi dysfunction may be the cause of biliarylike pain and is often considered in patients who remain uncomfortable after
cholecystectomy. The pathogenesis of the symptoms is thought to be similar to that of esophageal dysmotility and irritable bowel syndrome. Patients
typically experience severe, intermittent upper abdominal pain that lasts for 13 hours, sometimes following a meal.
Residual gallstone and pancreatic disease must first be ruled out. Ampullary dysfunction can then be diagnosed by sphincter of Oddi manometry.
Patients are placed in one of three groups depending on the presence of three objective manifestations of biliary obstruction: abnormal liver function
tests, prolonged (> 45 minutes) common bile duct emptying of contrast media after ERCP, and a common duct greater than 12 mm in diameter. Patients
in group I have all three findings; patients in group II have one or two findings; and patients in group III have none of the findings. Group I patients are
thought to have enough evidence of disease that sphincterotomy should be performed without manometry. Group I patients have abnormal motility
so rarely that they should not be considered further for sphincterotomy. Thus, motility studies are most often of value in determining which of the
group II patients will improve after sphincterotomy.
The abnormalities sought on the motility studies include an elevated (> 40 mm Hg) basal sphincter pressure and a paradoxic rise in sphincter pressure
in response to CCK. The former is most reliable. About 50% of group II patients have elevated sphincter pressures, and these are the patients who
benefit from sphincterotomy.
Patients are placed in one of three groups depending on the presence of three objective manifestations of biliary obstruction: abnormal liver function
tests, prolonged (> 45 minutes) common bile duct emptying of contrast media after ERCP, and a common duct greater than 12 mm in diameter. Patients
in group I have all three findings; patients in group II have one or two findings; and patients in group III have none of the findings. Group I patients are
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thought to have enough evidence of disease that sphincterotomy should be performed without manometry. Group I patients have abnormal motility
so rarely that they should not be considered further for sphincterotomy. Thus, motility studies are most often of value in determining which of the
group II patients will improve after sphincterotomy.
The abnormalities sought on the motility studies include an elevated (> 40 mm Hg) basal sphincter pressure and a paradoxic rise in sphincter pressure
in response to CCK. The former is most reliable. About 50% of group II patients have elevated sphincter pressures, and these are the patients who
benefit from sphincterotomy.
A scintigraphic test may be just as accurate. The patient is given a bolus of CCK followed by technetium99m–diisopropyl iminodiacetic acid (DISIDA).
Gamma camera images of the liver and bile duct are obtained for 60 minutes. A scoring system (score: 012) is based on the rate of passage of the
imaging agent past various relevant points (eg, appearance and clearance through the liver, bile duct, and bowel). The normal range is 05; abnormal is
612.
Sphincter of Oddi dysfunction is an uncommon explanation for abdominal pain, and it is appropriate to remain skeptical unless the objective findings
of biliary obstruction are clearcut. In wellselected cases, however, endoscopic sphincterotomy is beneficial.
Heetun ZS, Zeb F, Cullen G, et al: Biliary sphincter of Oddi dysfunction: response rates after ERCP and sphincterotomy in a 5year ERCP series and
proposal for new practical guidelines. Eur J Gastroenterol Hepatol . 2011;23(4):327–333. [PubMed: 21383625]
Duodenal Diverticula
Duodenal diverticula usually arise on the medial aspect of the duodenum within 2 cm of the orifice of the bile duct, and in some individuals, the duct
empties directly into a diverticulum. Even in the latter circumstance, duodenal diverticula are usually innocuous. Occasionally, distortion of the duct
entrance or obstruction by enterolith formation in the diverticulum produces symptoms. Either choledochoduodenostomy or RouxenY
choledochojejunostomy is usually a safer method of reestablishing biliary drainage than attempts to excise the diverticulum and reimplant the duct.
Ascariasis
When the worms invade the duct from the duodenum, ascariasis can produce symptoms of ductal obstruction. Air may sometimes be seen within the
ducts. Antibiotics should be used until cholangitis is controlled, and anthelmintic therapy (mebendazole, albendazole, or pyrantel pamoate) should
then be given. The acute symptoms usually subside with antibiotics, but if they do not, endoscopic sphincterotomy should be performed and attempts
made to extricate the worms. If this is unsuccessful and the patient remains acutely ill, the duct should be emptied surgically.
Recurrent Pyogenic Cholangitis
Cholangiohepatitis is a type of chronic recurrent cholangitis prevalent in coastal areas from Japan to Southeast Asia. In Hong Kong, it is the third most
common indication for emergency laparotomy and the most frequent type of biliary disease. The disease is currently thought to result from chronic
portal bacteremia, with portal phlebitis antedating the biliary disease. E coli causes secondary infection of the bile ducts, which initiates pigment stone
formation within the ducts.
Biliary obstruction from the stones gives rise to recurrent cholangitis, which, unlike gallstone disease in Western countries, may be unaccompanied by
gallbladder stones. The gallbladder is usually distended during an attack and may contain pus.
Chronic recurrent infection often leads to biliary strictures and hepatic abscess formation. The strictures are usually located in the intrahepatic bile
ducts, and for some unknown reason, the left lobe of the liver is more severely involved. Intrahepatic gallstones are common, and their surgical
removal may be difficult or impossible. Acute abdominal pain, chills, and high fever are usually present, and jaundice develops in about half of cases.
Right upper quadrant tenderness is usually marked, and in about 80% of cases, the gallbladder is palpable. ERCP, MRCP, or THC is the best way to study
the biliary tree and can help in determining the need for surgery and the type of procedure.
Systemic antibiotics should be given for acute cholangitis. Surgical treatment consists of cholecystectomy, common duct exploration, and removal of
stones. Sphincteroplasty should also be performed to allow any residual or recurrent stones to escape from the duct. A RouxenY
choledochojejunostomy is indicated for patients with strictures, markedly dilated ducts (eg, > 3 cm), or recurrent disease after a previous
sphincteroplasty. The results of surgery are good in 80% of patients. Chronic intrahepatic stones and infection, which often involve only one lobe, may
require hepatic lobectomy.
Although many patients are cured, prolonged illness from repeated infection is almost unavoidable once strictures have appeared or the intrahepatic
ducts have become packed with stones.
Systemic antibiotics should be given for acute cholangitis. Surgical treatment consists of cholecystectomy, common duct exploration, and removal of
stones. Sphincteroplasty should also be performed to allow any residual or recurrent stones to escape from the duct. A RouxenY
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choledochojejunostomy is indicated for patients with strictures, markedly dilated ducts (eg, > 3 cm), or recurrent disease after a previous
sphincteroplasty. The results of surgery are good in 80% of patients. Chronic intrahepatic stones and infection, which often involve only one lobe, may
require hepatic lobectomy.
Although many patients are cured, prolonged illness from repeated infection is almost unavoidable once strictures have appeared or the intrahepatic
ducts have become packed with stones.
Sclerosing Cholangitis
Sclerosing cholangitis is a rare chronic disease of unknown cause characterized by nonbacterial inflammatory narrowing of the bile ducts. About 60%
of cases occur in patients with ulcerative colitis, and sclerosing cholangitis develops in about 5% of patients with that disorder. Other less commonly
associated conditions are thyroiditis, retroperitoneal fibrosis, and mediastinal fibrosis. The disease chiefly affects men 2050 years of age. In most
cases, the entire biliary tree is affected by the inflammatory process, which causes irregular partial obliteration of the lumen of the ducts. The
narrowing may be confined, however, to the intrahepatic or extrahepatic ducts, although it is almost never so short as to resemble a posttraumatic or
focal malignant stricture. The woodyhard duct walls contain increased collagen and lymphoid elements and are thickened at the expense of the
lumen.
The clinical onset usually consists of the gradual appearance of mild jaundice and pruritus. Symptoms of bacterial cholangitis (eg, fever and chills) are
uncommon in the absence of previous biliary surgery. Laboratory findings are typical of cholestasis. The total serum bilirubin averages about 4 mg/dL
and rarely exceeds 10 mg/dL. MRCP/ERCP is usually diagnostic, demonstrating ductal stenoses and irregularity, which often gives a beaded
appearance. Liver biopsy may show pericholangitis and bile stasis, but the changes are nonspecific.
The complications of sclerosing cholangitis include gallstone disease and adenocarcinoma of the bile duct. The latter is most common in patients with
ulcerative colitis. Furthermore, patients with ulcerative colitis and sclerosing cholangitis appear to be at greater risk for colonic mucosal dysplasia and
colon cancer than those with ulcerative colitis not associated with sclerosing cholangitis.
Ursodiol (ursodeoxycholic acid), 10 mg/kg/d, improves liver function tests and symptoms. Cholestyramine will give relief from pruritus. Percutaneous
transhepatic balloon dilatation can be of value to treat dominant strictures. In cases where the disease is largely confined to the distal extrahepatic
duct and the proximal ducts are dilated, a RouxenY hepaticojejunostomy may be indicated. For patients with severe intrahepatic involvement, hepatic
transplantation should be considered.
The natural history of sclerosing cholangitis is one of chronicity and unpredictable severity. Some patients seem to obtain nearly complete remission
after treatment, but this is not common. Bacterial cholangitis may develop after operation if adequate drainage has not been established. In these
cases, antibiotics will be required at intervals. Most patients experience the gradual evolution of secondary biliary cirrhosis after many years of mild to
moderate jaundice and pruritus. Liver transplantation is indicated when the disease becomes advanced. The results are good.

Chapter 27 - Biliary Tract

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