Ch. 54 – Biliary System

Biliary System 

Ravi S. Chari, MD and Shimul A. Shah, MD 

Anatomy 

Physiology 

General Considerations in Biliary Tract Pathophysiology 

Benign Pathophysiologic Conditions 

Malignant Biliary Disease 

Although signs and symptoms of gallstones and extrahepatic 

biliary obstruction have been recognized for centuries, 

the surgical management of biliary tract disorders 

has evolved only recently. Advances in anesthesia, a 

better understanding of biliary anatomy and physiology, 

and improved surgical technique have allowed surgeons 

to manage both benign and malignant biliary disorders 

with increasing frequency and success in the past 10 

years. 

The fi rst biliary tract operation is credited to John 

Stough Bobb of Indianapolis in 1867. He explored a 32year-old 

woman with a large abdominal mass and discovered 

a massive gallbladder hydrops. Bobb made a 

cholecystotomy, removed the gallstones, and then sutured 

the gallbladder. In 1882, Carl Langenbuch of Berlin performed 

the fi rst cholecystectomy for a patient with biliary 

colic. The patient survived the operation and was discharged 

from the hospital 8 weeks after surgery. The 

treatment of calculous gallbladder disease was revolutionized 

again, more than 100 years later, in 1986 when 

Mühe performed the fi rst laparoscopic cholecystectomy. 

Since the late 19th century, the operative management 

of extrahepatic biliary obstruction also evolved rapidly. 

The fi rst biliary enteric anastomosis was performed by 

CHAPTER 54 

Alexander von Winiwarter in Liège in 1880 on a patient 

with common bile duct obstruction due to choledocholithiasis 

who underwent a cholecystocolostomy. Monastryski 

performed the fi rst palliative biliary bypass for 

malignant obstruction in 1887. Choledochotomy with 

stone extraction was fi rst performed in 1889. However, 

the high mortality associated with this procedure led to 

the use of cholecystojejunostomy for biliary obstruction. 

This was popularized by Ludwig Courvoisier, who 

reported his fi rst 10 cases in 1890 with an operative 

mortality rate of 20%. Choledochoduodenostomy was 

initially attempted for an impacted common duct stone 

by Oskar Sprengel in Germany in 1891 and then again 

following resection of a periampullary cancer in 1898 by 

William Stewart Halsted. The use of a Roux-en-Y jejunal 

limb to create a hepaticojejunostomy as commonly used 

today was fi rst reported by Robert Dahl of Stockholm in 

1909. 

Advances in a variety of diagnostic and nonoperative 

modalities have been made in the 20th century and have 

further refi ned the management of patients with biliary 

tract disease. The diagnosis of gallstones was improved 

considerably by the development of oral cholecysto graphy 

by Graham and Cole in 1924. In the 1950s, 

cholescintography and endoscopic and transhepatic 

cholangiography were developed, permitting nonoperative 

imaging of the biliary tract. More recently, ultrasonography, 

computed tomography (CT), magnetic 

resonance imaging (MRI), and laparoscopy have vastly 

improved the ability to image the biliary tract. The detail 

of the liver and biliary tract outlined by CT and magnetic 

resonance cholangiopancreatography (MRCP) has enabled 

the surgeon to approach operative cases with a clear 

understanding of the anatomy and relationships of important 

structures in the porta hepatitis. 

1547

1548 Section X Abdomen 

ANATOMY 

Cystic artery 

Common 

bile duct 

Right hepatic duct 

Left hepatic duct 

Pancreatic 

duct 

Extrahepatic Biliary Tract 

The extrahepatic biliary tract consists of the bifurcation 

of the left and right hepatic ducts, the common hepatic 

duct, the common bile duct, and the cystic duct and 

gallbladder (Fig. 54-1). The left hepatic duct is formed 

by the ducts draining segments II, III, and IV of the liver, 

courses horizontally along the base of segment IV, and 

has an extrahepatic length of about 2 cm. The right 

hepatic duct is formed by the right posterior (segments 

IV and VII) and right anterior (segments V and VIII) 

hepatic ducts and has a shorter extrahepatic length. The 

hepatic duct bifurcation is usually extrahepatic and anterior 

to the portal vein bifurcation. The biliary confl uence 

is separated from the posterior aspect of the caudate lobe 

(segment I) of the liver by the hilar plate, which consists 

of a fusion of connective tissue enclosing the biliary and 

vascular structures within the Glisson capsule (Fig. 54-2). 

The common hepatic duct lays anterolateral to the hepatic 

artery and portal vein in the hepatoduodenal ligament 

and joins the cystic duct to form the common bile duct. 

The common bile duct extends from the cystic duct– 

common hepatic duct junction inferiorly to the papilla of 

Fundus 

Right hepatic artery 

Corpus 

Portal vein 

Gastroduodenal artery 

Common hepatic artery 

Neck 

Figure 54-1 Anatomy of the biliary system and its relationship to surrounding structures. 

A 

B 

VI 

VII 

V 

VIII 

Papilla 

C 

IV 

Common 

hepatic duct 

Cystic duct 

Hartmann’s 

pouch 

Common 

bile duct 

Figure 54-2 Anatomy of the hilar plate. Note the cystic plate (A) 

above the gallbladder, the hilar plate (B) above the biliary confl uence, 

and the umbilical plate (C) above the umbilical portion of 

the portal vein. Large, curving arrows indicate plane of dissection 

of the cystic plate during cholecystectomy and of the hilar 

plate at the base of segment IV during approaches to the left 

hepatic duct. (From Blumgart LH, Hann LE: Surgical and radiological 

anatomy of the liver and biliary tract. In Blumgart LH, 

Fong Y [ed]: Surgery of the Liver and Biliary Tract. New York, 

WB Saunders, 2000, pp 13-14.) 

II 

III

Vater, where it empties into the duodenum. The common 

bile duct varies in length from 5 to 9 cm depending on 

its junction with the cystic duct and is divided into three 

segments: supraduodenal, retroduodenal, and intrapancreatic. 

The distal common bile duct and pancreatic duct 

may join outside the duodenal wall to form a long 

common channel, within the duodenal wall to form a 

short common channel, or they may enter the duodenum 

through two distinct ostia. 

The gallbladder is a pear-shaped reservoir in continuity 

with the common hepatic and common bile ducts 

through the cystic duct. It is usually 7 to 10 cm in length, 

is 3 to 5 cm in diameter, and has a capacity of 30 to 

60 mL. The gallbladder lies on the inferior surface of the 

liver partially enveloped in a layer of peritoneum. The 

gallbladder is anatomically divided into the fundus, body, 

infundibulum, and neck, which empties into the cystic 

duct. Both the gallbladder neck and the cystic duct 

contain spirally oriented mucosal folds known as the 

valves of Heister. The valves prevent the passage of gallstones 

and excessive distention or collapse of the cystic 

duct, despite variations in ductal pressure. The cystic duct 

varies in length from 1 to 5 cm and in diameter from 3 

to 7 mm; it usually joins the common hepatic duct at an 

acute angle. Small veins and lymphatics course between 

the gallbladder fossa and the gallbladder wall, connecting 

the lymphatic and venous drainage of the liver and gallbladder. 

These connections are the cause of the direct 

infl ammatory and carcinomatous spread from the gallbladder 

into the liver. 

Anatomic variations in the cystic duct and hepatic 

ducts are common. Frequent variations in the hepatic 

ductal anatomy are shown in Figure 54-3. Drainage to 

the caudate lobe (segment I) is not shown but can arise 

directly from common bile duct, right hepatic duct, or 

left hepatic duct. Variations of the left hepatic duct are 

much less common than those of the right hepatic duct. 

The cystic duct usually enters the common bile duct at 

an acute angle, but may run parallel to the common 

hepatic duct for a variable distance before joining it, or 

may join the right hepatic duct or a segmental right 

hepatic duct. An accessory hepatic duct or cholecystohepatic 

duct (duct of Luschka) may also enter the gallbladder 

through the gallbladder fossa and, if encountered 

during a cholecystectomy, should be ligated to prevent 

a biliary fi stula. 

Anomalies of the gallbladder are much less frequent 

than variations in ductal anatomy. Agenesis of the gallbladder 

has been reported (∼200 cases), and duplication 

of the gallbladder (two separate gallbladders, each with 

its own cystic duct) occurs in 1 of 4000 births. 

Vascular Anatomy 

The blood supply to the extrahepatic biliary tree originates 

(1) distally from the gastroduodenal, retroduodenal, 

and posterosuperior pancreatoduodenal arteries and (2) 

proximally from the right hepatic and cystic arteries. 

These arteries supply the common bile and common 

hepatic ducts through branches running parallel to the 

duct in the 3- and 9-o’clock positions. The extrahepatic 

ra 

rp lh 

A57% B12% 

ra 

rp lh 

Chapter 54 Biliary System 1549 

rp 

C20% 16% 4% 

C1 C2 

rp 

D6% 

ra 

rp 

E3% 

ra 

D1 

F2% 

5% 

lh 

2% 1% 

E1 E2 

rp 

I 

IV 

II 

ra 

biliary tree is vulnerable to ischemic injury. To avoid 

disrupting the fragile inconstant blood supply to the duct, 

it is important not to strip the investing areolar tissue 

around it during dissection and isolation. Ischemia of 

the bile duct will not be readily evident at time of 

dissection but can result in biliary stricture or leak 

postoperatively. 

rp 

rp 

ra 

ra 

rp 

ra 

ra 

lh 

1% 

D2 

Figure 54-3 Variations in the confl uence of the left and right 

hepatic ducts. A, Typical anatomy of the confl uence. B, Trifurcation 

of left, right anterior, and right posterior hepatic ducts. 

C, Aberrant drainage of a right anterior (C1) or posterior (C2) 

sectoral hepatic duct into the common hepatic duct. D-F, Less 

common variations in hepatic ductal anatomy. (From Smadja C, 

Blumgart L: The biliary tract and the anatomy of biliary exposure. 

In Blumgart L [ed]: Surgery of the Liver and Biliary Tract. 

New York, Churchill Livingstone, 1994, pp 11-24.) 

III 

IV 

I 

lh 

lh 

lh 

III 

II

1550 Section X Abdomen 

Cystic artery 

Cystic duct 

Common duct 

The gallbladder is supplied by a single cystic artery, 

but in 12% of cases, a double cystic artery (anterior and 

posterior) may exist. The origin and course of the cystic 

artery is highly variable and is one of the most variable 

in the body. The cystic artery may originate from the left 

hepatic, common hepatic, gastroduodenal, or superior 

mesenteric arteries. The cystic artery divides into superfi 

cial and deep branches before entering the gallbladder. 

The cystic artery usually lies superior to the cystic duct 

and passes posterior to the common hepatic duct, but its 

course varies with its origin. The common hepatic duct, 

the liver, and the cystic duct defi ne the boundaries of 

Calot’s triangle (Fig. 54-4). Located within this triangle 

are important structures: the cystic artery, the right hepatic 

artery, and the cystic duct lymph node. The Calot node 

is the main route of lymphatic drainage of the gallbladder 

and is therefore commonly involved in infl ammatory or 

neoplastic diseases of the gallbladder. 

PHYSIOLOGY 

X 

Hepatic duct 

Portal vein 

Hepatic artery 

Figure 54-4 The triangle of Calot is bounded by the cystic duct, 

the common hepatic duct, and the inferior border of the liver. 

(From Gilchrist BF, Trunkey DD, Biliary Tract trauma. In 

Zuidema GD [ed]: Shackelford’s surgery of the alimentary tract, 

3rd ed. WB Saunders, Philadelphia, 1991, pp 257.) 

Bile Ducts 

The bile ducts, gallbladder, and sphincter of Oddi modify, 

store, and regulate the fl ow of bile. The liver produces 

500 to 1000 mL of bile per day and excretes it into the 

bile canaliculi. During its passage through the bile ductules 

and hepatic duct, canalicular bile is modifi ed by the 

absorption and secretion of electrolytes and water. The 

secretion of bile is responsive to neurogenic, humoral, 

and chemical stimuli. Vagal stimulation increases bile 

secretion, whereas splanchnic nerve stimulation results 

in decreased bile fl ow. The gastrointestinal hormone, 

secretin, stimulates bile fl ow primarily by increasing the 

active secretion of chloride-rich fl uid by the bile ducts 

and ductules. Secretin release is stimulated by hydrochloric 

acid, proteins, and fatty acids in the duodenum. Bile 

ductular secretion is also stimulated by cholecystokinin 

(CCK), gastrin, and other hormones. The bile duct epi- 

thelium is also capable of water and electrolyte absorption, 

which may be of primary importance in the storage 

of bile during fasting in patients who have previously 

undergone cholecystectomy. 

Bile is composed of water, electrolytes, bile salts, proteins, 

lipids, and bile pigments. Sodium, potassium, 

calcium, and chlorine have the same concentration in bile 

as in plasma or extracellular fl uid. The primary bile salts, 

cholate and chenodeoxycholate, are synthesized in the 

liver by cholesterol. They are conjugated there with 

taurine and glycine, and act within the bile as anions 

(bile acids) that are balanced by sodium. Bile salts are 

excreted into the bile by the hepatocyte and aid in the 

digestion and absorption of fats in the intestines. About 

95% of the bile acid pool is reabsorbed and returned 

through the portal venous system to the liver, also known 

as the enterohepatic circulation (Fig. 54-5). The remaining 

5% is excreted in the stool. 

Cholesterol and phospholipids synthesized in the liver 

are the principal lipids found in bile. The synthesis of 

phospholipid and cholesterol by the liver is regulated in 

part by bile acids. The color of bile is due to the presence 

of the pigment bilirubin diglucuronide, which is the 

metabolic product from the breakdown of hemoglobin, 

and is present in bile in concentrations 100 times greater 

than plasma. Once in the intestine, bacteria convert it 

into urobilinogen, a small fraction of which is absorbed 

and secreted into the bile. 

Gallbladder 

The gallbladder concentrates and stores hepatic bile 

during the fasting state and delivers bile into the duodenum 

in response to a meal. Since the usual capacity of 

the gallbladder is only about 30 to 60 mL, the remarkable 

absorptive capacity of the gallbladder accounts for its 

ability to store much of the 600 mL of bile produced each 

day. The gallbladder mucosa has the greatest absorptive 

capacity per unit area of any structure in the body. Bile 

is usually concentrated 5- to 10-fold by the absorption of 

water and electrolytes leading to a marked change in bile 

composition. 

Active NaCl transport by the gallbladder epithelium is 

the driving force for the concentration of bile. Water is 

passively absorbed in response to the osmotic force generated 

by solute absorption. The concentration of bile 

may affect the solubility of two important components of 

gallstones: calcium and cholesterol. Although the gallbladder 

mucosa absorbs calcium, this process is not 

nearly as effi cient as for sodium or water, leading to 

greater relative increase in calcium concentration. As the 

gallbladder bile becomes concentrated, several changes 

occur in the capacity of bile to solubilize cholesterol. The 

solubility in the micellar fraction is increased, but the 

stability of phospholipid-cholesterol vesicles is greatly 

decreased. Because cholesterol crystal precipitation 

occurs preferentially by vesicular rather than micellar 

mechanisms, the net effect of concentrating bile is an 

increased tendency for cholesterol nucleation. 

The gallbladder epithelial cell secretes at least two 

important products into the gallbladder lumen: glycopro-

Urinary 

excretion 

(95% of biliary secretion) 

Synthesis 

(0.2–0.6 g/d) 

teins and hydrogen ions. Secretion of mucus glycoprotein 

occurs primarily from the glands of the gallbladder 

neck and cystic duct. The resultant mucin gel is believed 

to constitute an important part of the unstirred layer 

(diffusion-resistant barrier) that separates the gallbladder 

cell membrane from the luminal bile. This mucus barrier 

may be very important in protecting the gallbladder epithelium 

from the strong detergent effect of the highly 

concentrated bile salts found in the gallbladder. However, 

considerable evidence also suggests that mucin glycoproteins 

play a role as a pronucleating agent for cholesterol 

crystallization. The transport of hydrogen ions by the 

gallbladder epithelium leads to a decrease in gallbladder 

bile pH through a sodium-exchange mechanism. Acidifi - 

cation of bile promotes calcium solubility, thereby preventing 

its precipitation as calcium salts. The gallbladder’s 

normal acidifi cation process lowers the pH of entering 

hepatic bile from 7.5 to 7.8 down to 7.1 to 7.3. 

The gallbladder fi lls from the continuous production 

of bile by the liver against the force of a contracted 

sphincter of Oddi. As the pressure within the common 

bile duct exceeds that within the gallbladder lumen, 

hepatic bile enters the gallbladder by retrograde fl ow 

through the cystic duct, wherein it is rapidly concentrated. 

Periods of fi lling are punctuated by brief episodes 

of partial emptying (∼10%-15% of its volume) of concentrated 

gallbladder bile that are coordinated through the 

duodenum of phase III of the migrating myoelectric 

complex (MMC). 

Fecal excretion 

(0.2–0.6 g/d) 

Biliary secretion = pool x cycles 

(12–36 g/d) (~3 g) x (4–12/d) 

Chapter 54 Biliary System 1551 

Figure 54-5 Enterohepatic circulation. (From Arias IM, Popper H, Jakoby WB, et al: The liver: Biology and 

pathobiology. Philadelphia: Raven Press, 1988, p 576.) 

Following a meal, the gallbladder contracts in response 

to both a vagally mediated cephalic phase of activity and 

the release of CCK, the major regulator of gallbladder 

function. In the next 60 to 120 minutes, about 50% to 

70% of gallbladder bile is steadily emptied into the intestinal 

tract. CCK is localized to the proximal small intestine, 

especially the duodenal epithelial cells, where its 

release is stimulated by intraluminal fat, amino acids, and 

gastric acid and inhibited by bile. In addition to stimulating 

gallbladder contractions, CCK also acts to functionally 

inhibit the normal phasic motor activity of the sphincter 

of Oddi. Gallbladder refi lling then occurs gradually over 

the next 60 to 90 minutes. 

Sphincter of Oddi 

The sphincter of Oddi is a complex structure that is 

functionally independent from the duodenal musculature. 

It creates a high-pressure zone between the bile 

duct and the duodenum. The sphincter regulates the fl ow 

of bile and pancreatic juice into the duodenum, prevents 

the regurgitation of duodenal contents into the biliary 

tract, and also diverts bile into the gallbladder. The 

sphincter of Oddi also has very high-pressure phasic 

contractions, which play a role in preventing the regurgitation 

of duodenal contents into the biliary tract. 

Both neural and hormonal factors infl uence the sphincter 

of Oddi. In response to CCK, both sphincter of Oddi 

pressure and phasic wave activity diminish. After a meal,


Suspect common 

bile duct stones 

Lap cholecystectomy 

with IOC and lap CDBE 

or 

ERCP with stone extraction, 

papillotomy; lap cholecystectomy 

sphincter pressure relaxes in coordination with gallbladder 

contraction, thereby allowing the passive fl ow of bile 

into the duodenum. During fasting, high-pressure phasic 

contractions of the sphincter of Oddi persist through all 

phases of the MMC. Sphincter of Oddi activity appears 

to be coordinated with the partial gallbladder emptying 

and increases in the bile fl ow that occur during phase III 

of the MMC. This activity may be a preventive mechanism 

against the accumulation of biliary crystals during 

fasting. 

GENERAL CONSIDERATIONS IN BILIARY 

TRACT PATHOPHYSIOLOGY 

Suspect extrahepatic 

biliary obstruction 

Ultrasound 

Symptoms 

Symptoms attributable to biliary tract pathology are 

usually the result of obstruction, infection, or both. 

Obstruction can be extramural (e.g., pancreatic cancer), 

intramural (cholangiocarcinoma), or intraluminal (cho- 

Jaundice 

History and physical 

Dilated ducts Normal ducts 

Proximal obstruction 

Palliative 

PTC 

Suspect malignant 

obstruction 

3-phase 

CT scan 

with venous delay 

Operation 

Suspect intrahepatic 

disease 

CT scan to rule out liver mass 

Hepatitis screen 

Possible liver biopsy 

Distal obstruction 

Palliative 

ERCP 

Figure 54-6 Diagnostic algorithm for patients presenting with jaundice. CBDE, common bile duct exploration; CT, 

computed tomography; ERCP, endoscopic retrograde cholangiopancreatography; IOC, intraoperative cholangiogram; 

lap, laparoscopic; PTC, percutaneous transhepatic cholangiography. 

ledocholithiasis). Similar to infections in other parts of 

the body, biliary infections are usually due to three 

factors: a susceptible host, suffi cient inoculum, and stasis. 

The most common symptoms related to biliary tract 

disease are abdominal pain, jaundice, fever, and nausea 

and vomiting. 

Abdominal Pain 

Gallstones and infl ammation of the gallbladder are the 

most frequent causes of abdominal pain from biliary tract 

disease. Acute obstruction of the gallbladder by calculi 

results in biliary colic, a common misnomer because the 

pain is not colicky in the epigastrium or right upper 

quadrant. Biliary colic is a constant pain that builds in 

intensity, and can radiate to the back, interscapular 

region, or right shoulder. The pain is described as a 

bandlike tightness of the upper abdomen that may be 

associated with nausea and vomiting. This is due to a 

normal gallbladder contracting against a luminal obstruction, 

such as a gallstone impacted in the neck of the 

gallbladder, the cystic duct, or the common bile duct.

The pain is most commonly triggered by fatty foods, but 

it can also be initiated by other types of food or even 

occur spontaneously. An association with meals is present 

in only 50% of patients, and in these patients, the pain 

often develops more than 1 hour after eating. 

The pain of biliary colic is distinct from that associated 

with acute cholecystitis. Although biliary colic can also 

be localized to the right upper quadrant, the pain of acute 

cholecystitis is exacerbated by touch, is somatic in nature, 

and is often associated with fever and leukocytosis. Irritation 

of the visceral and parietal peritoneum due to transmural 

infl ammation from cholecystitis results in a positive 

Murphy’s sign. This physical exam fi nding (in a patient 

abruptly arresting his or her inspiratory effort because of 

pain as the examiner palpates under the right costal 

margin) is indicative of acute cholecystitis. 

Jaundice 

When the serum concentration of bilirubin exceeds about 

2.5 mg/dL, a yellowish discoloration of the sclera becomes 

evident (scleral icterus). Jaundice represents a similar 

discoloration of the skin, with serum bilirubin levels in 

excess of 5 mg/dL. The changes in color represent deposition 

of bile pigments in the affected tissues. The presence 

of conjugated bilirubin in the urine is one of the 

fi rst changes noted by patients. 

Workup and diagnosis of the jaundiced patient require 

an algorithm similar that in to Figure 54-6. Disorders 

resulting in jaundice can be divided into those causing 

“medical” jaundice, such as increased production, 

decreased hepatocyte transport or conjugation, or 

impaired excretion of bilirubin, and those causing “surgical” 

jaundice through impaired delivery of bilirubin into 

the intestine. Common causes of increased bilirubin production 

include the hemolytic anemias and acquired 

causes of hemolysis, including sepsis, burns, transfusion 

reactions, and medications. Impaired excretion of bilirubin 

leads to intrahepatic cholestasis and conjugated 

hyperbilirubinemia and can be due to conditions like 

viral or alcoholic hepatitis, cirrhosis, and drug-induced 

cholestasis. 


Table 54-1 Accuracy of Preferred Imaging Modalities for Different Biliary Tract Diagnoses Causing Right Upper Quadrant Pain 

SUSPECTED DIAGNOSIS IMAGING MODALITY SENSITIVITY (%) SPECIFICITY (%) 

Cholelithiasis Ultrasound 95 99 

Acute calculous cholecystitis Ultrasound 88 80 

HIDA 95 95 

Acute acalculous cholecystitis Ultrasound 36-93 17-89 

HIDA 70-80 90-100 

Choledocholithiasis ERCP 95 89 

MRC 95 98 

I/OP cholangiogram 78 97 

Lap ultrasound 80 99 

Biliary dyskinesia HIDA 94 80 

ERCP, endoscopic retrograde cholangiopancreatography; HIDA, cholecystokinin hepatobiliary 2,6-dimethyl-iminodiacetic acid scan; I/OP, intraoperative; 

Lap, laparoscopic; MRC, magnetic resonance cholangiography. 

From Trowbridge RL, Rutkowski NK, Shojania KG: Does this patient have acute cholecystitis? JAMA 289:80-86, 2003. 

Fever 

Signifi cant elevations in body temperature (≥38.0°C) represent 

a systemic manifestation of an initially localized 

infl ammatory process. Bacterial contamination of the 

biliary system is a common feature of acute cholecystitis 

or choledocholithiasis with obstruction, and can be 

expected following percutaneous or endoscopic cholangiography. 

The combination of right upper quadrant 

abdominal pain, jaundice, and fever, known as Charcot’s 

triad, signifi es an active infection of the biliary system 

termed acute cholangitis. The addition of an altered 

mental status and hypotension to the above fi ndings 

represents severe cholangitis and is termed pentad of 

Reynolds. 

Laboratory Tests 

Biliary colic, in the absence of gallbladder wall pathology 

or common bile duct obstruction, does not produce 

abnormal laboratory test values. On the other hand, 

obstructive choledocholithiasis is commonly associated 

with both liver dysfunction and acute cellular injury with 

resultant elevations in liver function tests. Hepatocellular 

injury results in increased levels of unconjugated or indirect 

reacting bilirubin due to an increase in bilirubin 

production or a decrease in hepatocyte uptake with conjugation. 

Conjugated or direct hyperbilirubinemia is due 

to defects in bilirubin excretion (intrahepatic cholestasis) 

or extrahepatic biliary obstruction. In addition to hyperbilirubinemia, 

an increased alkaline phosphatase level 

is virtually pathognomonic of bile duct obstruction. In 

patients with a high clinical suspicion of cholecystitis, but 

with associated elevations of bilirubin, alkaline phosphatase, 

and aminotransferase, cholangitis should be suspected. 

Serum transaminase (aspartate and alanine) levels 

can also be mildly elevated in biliary system disease, 

either because of direct injury of the liver adjacent to an 

infl amed gallbladder or from the effect of biliary sepsis 

on hepatocellular membrane integrity. Leukocytosis, 

composed primarily of neutrophils, is often present with 

acute cholecystitis or cholangitis, but is a nonspecifi c

1554 Section X Abdomen 

Figure 54-7 Ultrasound of liver identifying mass at hepatic duct 

bifurcation (long arrow), pressing on confl uence of right and 

left hepatic ducts (short arrow). 

fi nding that does not distinguish them from other infectious 

or infl ammatory causes. 

Studies 

Plain Radiographs 

Although frequently obtained during the initial evaluation 

of abdominal pain, plain radiographs of the abdomen in 

patients with complaints localized to the right upper 

quadrant are rarely helpful. Only about 15% of gallstones 

contain enough calcium to render them radiopaque and 

therefore visible on plain abdominal fi lms. Plain fi lms are 

important to exclude other potential diagnoses, such as 

perforated ulcer with free intraperitoneal air, bowel 

obstruction with dilated loops of bowel, or right lower 

lobe pneumonia on chest x-ray, that may mimic biliary 

tract disease. 

Ultrasonography 

Ultrasound of the abdomen is an extremely useful and 

accurate method for identifying gallstones and pathologic 

changes in the gallbladder consistent with acute cholecystitis. 

Abdominal ultrasound, if performed by an experienced 

operator, should be part of the routine evaluation 

of patients suspected of having gallstone disease, given 

the high specifi city (>98%) and sensitivity (>95%) of this 

test for the diagnosis of cholelithiasis 1 (Table 54-1). In 

addition to identifying gallstones, ultrasound can also 

detail signs of cholecystitis such as thickening of the 

gallbladder wall, pericholecystic fl uid, and impacted 

stone in the neck of the gallbladder. It is often the initial 

Figure 54-8 CT cholangiogram shows enhanced imaging of the 

biliary system comparable to MRC. Intrahepatic and extrahepatic 

biliary ducts are clearly seen in this patient for evaluation for 

living donor right hepatectomy. 

screening test for patients with suspected extrahepatic 

biliary obstruction (Fig. 54-7). Dilation of the extrahepatic 

(>10 mm) or intrahepatic (>4 mm) bile ducts suggests 

biliary obstruction. Intraoperative ultrasound is now used 

frequently to further evaluate intrahepatic lesions, assess 

resectability, and determine involvement of vascular 

structures. 2 

Oral Cholecystography 

Once considered the diagnostic test of choice for gallstones, 

oral cholecystography has been replaced by ultrasonography. 

It identifi es fi lling defects in a visualized, 

opacifi ed gallbladder after oral administration of a radiopaque 

compound that passes into the gallbladder. Oral 

cholecystography is of no value in patients with vomiting, 

biliary obstruction, jaundice, or hepatic failure. 

Computed Tomography 

Although abdominal CT scanning is probably the most 

informative single radiographic tool for examining intraabdominal 

pathology, its overall value for the diagnosis 

of biliary tract disease pales in comparison to ultrasonography. 

The disadvantage is largely because gallstones and 

bile appear nearly isodense on CT; that is, it is diffi cult 

to distinguish gallstones from bile, unless the stones are 

heavily calcifi ed. CT identifi es gallstones within the biliary 

tree and gallbladder with a sensitivity of only about 55% 

to 65%. Conversely, CT is more accurate at identifying 

the site and cause of extrahepatic biliary obstruction. 

Abdominal CT is a powerful tool for evaluating biliary 

tract disease when the differential diagnosis includes a 

question of hepatobiliary or pancreatic neoplasm, liver 

abscess, or hepatic parenchymal disease (e.g., biliary cirrhosis, 

organ atrophy). Use of CT cholangiogram provides 

improved defi nition of the biliary tract comparable 

to magnetic resonance cholangiography (MRC; Fig. 54-8). 

Angiograms have now essentially been replaced by triplephase 

liver CT angiogram.

Cholangiography 

Cholangiography functionally involves the installation of 

contrast directly into the biliary tree and is the most 

accurate and sensitive method available to anatomically 

delineate the intrahepatic and extrahepatic biliary tree. It 

is most useful when the precise location or cause of 

biliary pathology needs to be ascertained. MRC is noninvasive 

and provides excellent anatomic detail. No contrast 

is administered because bile/water density is 

phase-contrasted. CT cholangiography requires the 

administration of intravenous (IV) contrast that is excreted 

in the biliary system. Neither of these is considered 

invasive. Both endoscopic retrograde cholangiopancreatography 

(ERCP) and percutaneous transhepatic cholangiography 

(PTC) are invasive procedures with a 2% to 

5% risk of complications but offer the opportunity for a 

therapeutic intervention. ERCP is most useful in imaging 

patients with hepatobiliary malignancies and choledocholithiasis. 

It illustrates distal common bile duct or 

ampullary obstruction, can provide tissue samples for 

pathologic diagnosis, and can palliate patients with complete 

biliary obstruction using prosthetic stents. However, 

it gives no information regarding tumor size, local invasion, 

or distant spread, and is of limited use in staging. 2 

Transhepatic cholangiography is the preferred technique 

in patients with proximal biliary obstruction or in patients 

in whom ERCP is not technically possible. Percutaneous 

transhepatic cholangiography can be followed by placement 

of transhepatic catheters, which can decompress 

the biliary system, function as anatomical landmarks 

during surgical reconstruction, or provide access for nonoperative 

dilation of strictures. 

Scintigraphy 

Biliary scintigraphy is useful to visualize the biliary tree, 

assess liver and gallbladder function, and diagnose several 

common disorders including cholecystitis. Although it is 

an excellent test to decide whether the common bile and 

cystic ducts are patent, biliary scintigraphy does not 

identify gallstones or give any detailed anatomic information. 

Nonvisualization of the gallbladder at 2 hours after 

injection is reliable evidence of cystic duct obstruction. 

Biliary scintigraphy followed by CCK administration is 

helpful for documenting biliary dyskinesia when gallbladder 

contraction accompanies biliary tract pain in 

patients without evidence of stones (CCK hepatobiliary 

2,6-dimethyl-iminodiacetic acid [HIDA]). These agents are 

iminodiacetic acid (IDA)-based compounds and are processed 

in the liver and excreted (H originally stood for 

hydroxy, but today stands for hepatobiliary because other 

IDA derivatives, such as proisopropyl-IDA [PIPIDA], are 

more commonly used, but are still referred to as HIDA 

scans). 

Laparoscopy 

Advancement in laparoscopic skill has coincided with the 

increased use of laparoscopy for diagnosis and treatment 

of biliary tract disorders. It is most effective when used 

in conjunction with laparoscopic ultrasound in the staging 

and operative management of biliary malignancies. Intra- 


operative ultrasound is now used frequently to further 

evaluate intrahepatic lesions, assess resectability, and 

determine involvement of vascular structures. 2,3 Although 

the need for laparoscopy may have diminished as a result 

of advancements in radiologic techniques like CT, laparoscopy 

still best identifi es micrometastases much beyond 

the discrimination of the CT scan; in addition, biopsy 

of micrometastases can be undertaken with the 

laparoscope. 

FDG-PET Scanning 

Fluorodeoxyglucose positron emission tomography 

(FDG-PET) is a whole-body technique that allows detection 

of unsuspected metastases that may lead to major 

changes in the surgical management of these patients. 

PET imaging with the fl uorinated glucose analogue, 

18 FDG, can be used to exploit the metabolic differences 

between benign and malignant cells for imaging purposes. 

Therefore, 18 FDG-PET imaging has become well 

established for differentiation of benign from malignant 

lesions, staging malignant lesions, detection of malignancy 

recurrence, and monitoring therapy for various 

malignancies (Fig. 54-9). Recent studies have shown that 

18 FDG-PET is accurate in predicting the presence of 

nodular cholangiocarcinoma (mass >1 cm) and gallbladder 

carcinoma (sensitivity, 78%). 4 18 FDG-PET is not useful 

for detection of carcinomatosis, and infl ammatory changes 

related to biliary stents may cause interpretation 

diffi culties. 

Bacteriology 

Local recurrence 

Metastasis 

Figure 54-9 Fluorodeoxyglucose positron emission tomography 

(FDG-PET) imaging in a patient undergoing surveillance after 

treatment for cholangiocarcinoma. The FDG-PET images demonstrate 

FDG uptake corresponding to the hilum on the respective 

CT image, indicating local recurrence and metastatic spread. 

Bile in the gallbladder or bile ducts in the absence of 

gallstones or any other biliary tract disease is normally 

sterile. In the presence of gallstones or biliary obstruction, 

the prevalence of bactibilia increases. The percentage 

of positive gallbladder bile cultures among patients 

with symptomatic gallstones and chronic cholecystitis 

ranges from 11% to 30%. The prevalence of positive 

gallbladder bile cultures is higher in patients with acute


Box 54-1 Common Bacterium Species 

Found in Biliary Tract Infections* 

Enterobacteriaceae (68% incidence) 

Escherichia coli 

Klebsiella species 

Enterobacter species 

Enterococcus species (14% incidence) 

Anaerobes (10% incidence) 

Bacteroides species 

Clostridium species (7% incidence) 

Streptococcus species (rare) 

Pseudomonas species (rare) 

Candida species (rare) 

*Cholecystitis, cholangitis, biliary sepsis, or common duct obstruction. 

From Thompson JE Jr, Pitt HA, Doty JE, et al: Broad spectrum penicillin 

as an adequate therapy for acute cholangitis. Surg Gynecol Obstet 

1990;171:275-282. 

cholecystitis than chronic cholecystitis (46% versus 22%) 

and increases further in the presence of common bile 

duct stones. Positive bile cultures are signifi cantly more 

common in elderly (>60 years) patients with symptomatic 

gallstones than in younger patients (45% versus 16%). 5,6 

Gram-negative aerobes are the organisms most frequently 

isolated from bile in patients with symptomatic gallstones, 

acute cholecystitis, or cholangitis (Box 54-1). 

Escherichia coli and Klebsiella species are the most 

common gram-negative bacteria isolated. However, Pseudomonas 

and Enterobacter species are being seen with 

increased frequency, particularly in patients with malignant 

biliary obstruction. 5 Other common isolates include 

the gram-positive aerobes, Enterococcus species, and 

Streptococcus viridans. Anaerobic bacteria, such as Bacteroides 

and Clostridium species, are infrequent but 

remain signifi cant pathogens in biliary infections. Candida 

species are also being increasingly recognized as a signifi 

cant biliary pathogen particularly in critically ill 

patients. 

The source of bacteria in patients with biliary tract 

infections is controversial. Most theories favor an ascending 

route through the duodenum as the main source of 

biliary bacteria. The bacterial fl ora in the small intestine 

is similar to that detected in the biliary tract. 

Antibiotic Selection 

Antibiotics should be used prophylactically in most 

patients undergoing elective biliary tract surgery or other 

biliary tract manipulations such as ERCP or PTC. In lowrisk 

patients undergoing laparoscopic cholecystectomy 

for biliary colic or chronic cholecystitis, there is no benefi t 

of prophylactic antibiotics. In high-risk patients, such as 

elderly patients, patients with recent acute cholecystitis, 

and those with high risk for conversion to open cholecystectomy, 

a single dose of the fi rst-generation cephalosporin, 

cefazolin, provides good coverage against the 

gram-negative aerobes commonly isolated from bile and 

skin fl ora. 

Box 54-2 Risk Factors for Gallstones 

Obesity* 

Rapid weight loss 

Childbearing 

Multiparity 

Female sex 

First-degree relatives 

Drugs: ceftriaxone, postmenopausal estrogens, total parenteral 

nutrition 

Ethnicity: Native American (Pima Indian), Scandinavian 

Ileal disease, resection or bypass 

Increasing age 

*Obesity is defi ned as body mass index greater than 30 kg/m2 . 

Adapted from Bellows CF, Berger DH, Crass RA: Management of 

gallstones. Am Fam Physician 72:637-642, 2005. 

Therapeutic antibiotics should be used in patients with 

acute cholecystitis and cholangitis and should cover 

gram-negative aerobes, gram-positive coverage, and 

anaerobes. 

BENIGN PATHOPHYSIOLOGIC CONDITIONS 

Calculous Biliary Disease 

Epidemiology 

Gallstones are among the most common gastrointestinal 

illness requiring hospitalization and frequently occur in 

young, otherwise healthy people with a prevalence of 

11% to 36% in autopsy reports. Female sex, obesity, 

pregnancy, fatty foods, Crohn’s disease, terminal ileal 

resection, gastric surgery, hereditary spherocytosis, sickle 

cell disease, and thalassemia are all associated with an 

increased risk for developing gallstones 7 (Box 54-2). Only 

fi rst-degree relatives of patients with gallstones and 

obesity (defi ned as body mass index >30 kg/m 2 ) have 

been identifi ed as strong risk factors for development of 

symptomatic gallstone disease. 8 

Gallstone Pathogenesis 

Gallstones represent an inability to maintain certain 

biliary solutes, primarily cholesterol and calcium salts, in 

a solubilized state. Gallstones are classifi ed by their cholesterol 

content as either cholesterol or pigment stones. 

Pigment stones are further classifi ed as either black or 

brown. Pure cholesterol gallstones are uncommon (10%), 

with most cholesterol stones containing calcium salts in 

their center, or nidus. In the United States, 70% to 80% 

of gallstones are cholesterol, and black pigment stones 

account for most of the remaining 20% to 30%. 

Biliary sludge refers to a mixture of cholesterol crystals, 

calcium bilirubinate granules, and a mucin gel matrix. 

It is most commonly found in prolonged fasting states or 

with the use of parental nutrition. The fi nding of macromolecular 

complexes of mucin and bilirubin suggests 

that sludge may serve as the nidus for gallstone 

pathogenesis.

Cholesterol Gallstones 

The pathogenesis of cholesterol gallstones involves three 

stages: 

1. Cholesterol supersaturation in bile 

2. Crystal nucleation 

3. Stone growth 

Gallbladder mucosal and motor function plays a key 

role in gallstone formation. The key to maintaining 

cholesterol in solution is the formation of micelles, a bile 

salt–phospholipid-cholesterol complex, and cholesterolphospholipid 

vesicles. In states of excess cholesterol 

production, these large vesicles may also exceed their 

capability to transport cholesterol, and crystal precipitation 

may occur. One third of biliary cholesterol is transported 

in micelles, but the cholesterol-phospholipid 

vesicles carry the majority of biliary cholesterol. By plotting 

the percentages of each component on triangular 

coordinates, the micellar zone in which cholesterol is 

completely soluble can be demonstrated (Fig. 54-10). In 

the area above the curve, bile is supersaturated with 

cholesterol, and precipitation of cholesterol crystals can 

occur. 

Pigment Gallstones 

Pigment stones contain less than 20% cholesterol and are 

dark owing to the presence of calcium bilirubinate. Otherwise, 

black and brown pigment stones have little in 

common and should be considered as separate entities. 

Black pigment stones are small and tarry, and are frequently 

associated with hemolytic conditions such as 

hereditary spherocytosis and sickle cell disease or cir- 

60 

40 

2 

phases 

Percent cholesterol 

20 

80 

1 phase 

100 

3 

phases 

20 

Ch crystals 

Micelles 

Lamelar 

2 

phases 

40 

Percent lecithin 

60 

1 

phase 

100 80 60 40 20 

Percent Na taurocholate 

80 

100 


Figure 54-10 Triangular-phase diagram with axes plotted in percent cholesterol, lecithin (phospholipid), and the 

bile salt sodium taurocholate. Below the solid line, cholesterol is maintained in solution in micelles. Above the 

solid line, bile is supersaturated with cholesterol and precipitation of cholesterol crystals can occur. Ch, cholesterol. 

(From Donovan JM, Carey MC: Separation and quantitation of cholesterol “carriers” in bile. Hepatology 

12:94S, 1990.) 

rhosis. In hemolytic states, the bilirubin load and concentration 

of unconjugated bilirubin increases. Cirrhosis 

may lead to increased secretion of unconjugated bilirubin. 

These stones are usually not associated with infected 

bile and are located almost exclusively in the gallbladder. 

Black stones account for a high percentage of gallstones 

in Asian countries such as Japan compared with the 

Western hemisphere. 

Brown pigment stones are soft and earthy in texture 

and are typically found in bile ducts, especially in Asian 

populations. Brown stones often contain more cholesterol 

and calcium palmitate and occur as primary common 

duct stones in Western patients with disorders of biliary 

motility and associated bacterial infection. Bacteria producing 

slime such as E. coli secrete β-glucuronidase that 

causes enzymatic hydrolysis of soluble conjugated bilirubin 

glucuronide to produce insoluble free bilirubin, 

which then precipitates with calcium. 9 

Natural History 

Most patients remain asymptomatic from their gallstones. 

Although the mechanism is unclear, some patients 

develop symptomatic gallstones, with biliary colic caused 

by a stone obstructing the cystic duct. Additional complications 

related to gallstones include acute cholecystitis, 

choledocholithiasis with or without cholangitis, gallstone 

pancreatitis, gallstone ileus, and gallbladder carcinoma. 

Gallstones are commonly found incidentally at laparotomy 

or on imaging either by ultrasonography or CT 

scan. Only 1% to 2% of asymptomatic individuals with 

gallstones develop serious symptoms or complications 

related to their gallstones per year; therefore, only about 

1% require a cholecystectomy. Once symptomatic,


patients tend to have recurring symptoms, usually 

repeated episodes of biliary colic. 10 Over a 20-year period, 

two thirds of asymptomatic patients with gallstones 

remain symptom-free. 

Chronic Calculous Cholecystitis 

Ongoing infl ammation with recurrent episodes of biliary 

colic or pain from cystic duct obstruction is referred to 

as chronic cholecystitis. About two thirds of patients with 

gallstone disease present with these repeated attacks. 

Although the pathologic changes in the gallbladder can 

vary, repeated attacks, scarring, and a nonfunctioning 

gallbladder are the rule. Histologically, chronic cholecystitis 

is characterized by an increase in subepithelial and 

subserosal fi brosis and a mononuclear cell infi ltrate. 

Clinical Presentation 

The primary symptom of chronic cholecystitis or symptomatic 

cholelithiasis is pain, often referred to as biliary 

colic (see earlier section, Abdominal Pain). The pain is 

constant and usually lasts 1 to 5 hours. The attacks 

usually last for more than 1 hour but subsides by 24 

hours; if pain persists longer than 1 day, acute cholecystitis 

is likely the underlying etiology. The attacks are discrete 

and severe enough that patients can accurately 

recall and number them. Other symptoms such as nausea 

and vomiting often accompany each episode, and bloating 

and belching may also be present in 50% of cases. 

Fever and jaundice are rare with simple biliary colic. 

Patients without symptoms, about two thirds of patients 

with gallstones, develop symptoms infrequently and 

complications at an even lower rate. In most cases, treatment 

is not necessary in these asymptomatic patients. 

Patients with gallstones but an atypical presentation 

should have other causes of right upper quadrant pain 

ruled out such as peptic ulcer disease, pneumonia, renal 

calculi, liver disease, hernia, refl ux, or angina. 

The physical examination and liver function tests are 

usually completely normal in patients with chronic cholecystitis, 

particularly if they are pain-free. During an 

episode of biliary colic, mild right upper quadrant tenderness 

may also be present. 

Diagnosis 

The diagnosis of symptomatic gallstones or chronic calculous 

cholecystitis relies on the clinical presentation and 

evidence of gallstones on diagnostic imaging. The presence 

of symptoms, typically biliary colic, attributable to 

the gallbladder is necessary to consider any treatment for 

gallstones. An abdominal ultrasound is the standard diagnostic 

exam for gallstones (Fig. 54-11). Ultrasonography 

also provides important anatomic information for the 

surgeon—presence of polyps, common bile duct diameter, 

or any hepatic parenchymal abnormalities. Occasionally, 

patients with typical attacks of biliary pain have no 

evidence of stones on ultrasonography, or only sludge is 

present. If the patient has recurrent attacks of typical 

biliary colic and sludge is detected on two or more occasions, 

cholecystectomy is indicated. In addition to sludge 

and stones, cholesterolosis and adenomyomatosis of the 

gallbladder may cause typical biliary symptoms and may 

be detected on ultrasonography. Cholesterolosis is caused 

by the accumulation of cholesterol in macrophages in the 

gallbladder mucosa, either locally or as polyps. It produces 

the classic macroscopic appearance of a “strawberry 

gallbladder.” Granulomatous polyps develop in the 

lumen at the fundus; the gallbladder wall is thickened, 

and septa or strictures may be seen in the gallbladder. 

In patients with these symptoms, cholecystectomy is the 

treatment of choice. 

Management 

The optimal treatment for patients with symptomatic 

cholelithiasis is elective laparoscopic cholecystectomy 

(Box 54-3). Patients should be advised to avoid dietary 

fats and large meals while awaiting surgery. Diabetic 

patients should have a cholecystectomy promptly because 

they are at higher risk for acute cholecystitis or even 

gangrenous cholecystitis. Pregnant women with symp- 

Figure 54-11 Gallbladder ultrasound in patient with biliary colic 

demonstrating multiple dependent echogenic foci with posterior 

acoustic shadowing consistent with gallstones. 

Box 54-3 Indications for Cholecystectomy 

Urgent* 

Acute cholecystitis 

Emphysematous cholecystitis 

Empyema of the gallbladder 

Perforation of the gallbladder 

Previous choledocholithiasis with endoscopic duct clearance 

Elective 

Biliary dyskinesia 

Chronic cholecystitis 

Symptomatic cholelithiasis 

*Within 24 to 72 hours.

tomatic gallstones who fail expectant management with 

dietary modifi cation can safely undergo surgery during 

the second trimester. Cholecystectomy offers excellent 

long-term results for patients with symptomatic gallstones. 

About 90% of patients are rendered symptom-free 

after cholecystectomy. For patients with atypical symptoms 

or painless dyspepsia (fatty food intolerance, fl atulence, 

belching, or bloating), the percentage of patients 

experiencing relief of symptoms falls. 

Acute Calculous Cholecystitis 

Pathophysiology 

Acute cholecystitis is related to gallstones in 90% to 95% 

of cases. Obstruction of the cystic duct leading to biliary 

colic is the initial event in acute cholecystitis. If the cystic 

duct remains obstructed, the gallbladder distends, and 

the gallbladder wall then becomes infl amed and edematous. 

Initially, acute cholecystitis is an infl ammatory 

process with a thickened and reddish wall with subserosal 

hemorrhage. The mucosa may show hyperemia and 

patchy areas of necrosis. In the most common scenario, 

the gallstone dislodges, and the infl ammation will gradually 

resolve. In the most severe cases, this process can 

lead to ischemia and necrosis of the gallbladder wall 

(5%-10%). Acute gangrenous cholecystitis results in formation 

of an abscess or empyema within the gallbladder. 

When gas-forming organisms are part of the secondary 

bacterial infection, gas may be seen in the gallbladder 

lumen and in the wall of the gallbladder on imaging 

resulting in emphysematous cholecystitis. 


Right upper quadrant pain, similar in severity to but much 

longer in duration than pain from previous episodes of 

biliary colic, is the most common symptom of acute 

cholecystitis. Other common symptoms include fever, 

nausea, and vomiting. On physical exam, right upper 

quadrant tenderness and guarding are usually present 

inferior to the right costal margin, distinguishing the 

episode from simple biliary colic. When infl ammation 

spreads to the peritoneum, patients develop more diffuse 

tenderness, guarding and rigidity. A mass, the gallbladder 

and adherent omentum, is occasionally palpable, and 

Murphy’s sign, inspiratory arrest with deep palpation in 

the right upper quadrant, may also be present. A mild 

leukocytosis is usually present (12,000-14,000 cells/mm 3 ). 

In addition, mild elevations in serum bilirubin (>4 mg/ 

dL), alkaline phosphatase, the transaminases, and amylase 

may be present. Severe jaundice is suggestive of common 

bile duct stones or obstruction of the bile ducts by severe 

pericholecystic infl ammation secondary to impaction of 

a stone in the infundibulum of the gallbladder that 

mechanically obstructs the bile duct, known as Mirizzi’s 

syndrome. 

Diagnosis 

Ultrasound is the most useful radiographic test for diagnosing 

acute cholecystitis, with sensitivity and specifi city 

of 85% and 95%, respectively. It is sensitive for identifying 

the presence of gallstones. Ultrasound also shows the 


presence of thickening of the gallbladder wall (>4 mm), 

pericholecystic fl uid, gallbladder distention, impacted 

stone, and a sonographic Murphy’s sign (focal tenderness 

directly over the gallbladder). 

Biliary radionuclide scanning is used less frequently 

today but may be helpful in atypical cases. No fi lling of 

the gallbladder with the radiotracer ( 99m Tc-HIDA) after 4 

hours indicates an obstructed cystic duct with a sensitivity 

and specifi city for acute cholecystitis of 95%. A normal 

HIDA scan excludes acute cholecystitis. However, when 

the patient is fasting for more than 5 days, HIDA scan is 

much less helpful, with a 40% false-positive rate. CT scan, 

although performed frequently in patients with abdominal 

pain, may identify some of the fi ndings mentioned 

previously, similar to ultrasonography, but is less sensitive 

than ultrasonography for acute cholecystitis. 

Management 

After the diagnosis of acute cholecystitis is made, IV 

fl uids, antibiotics, and analgesia should be initiated. Antibiotics 

should cover gram-negative aerobes as well as 

anaerobes (see Box 54-1). More than half of patients with 

acute cholecystitis have positive cultures from the gallbladder 

bile. Because it is diffi cult to know who is secondarily 

infected, IV antibiotics are an appropriate part 

of the management. 

Cholecystectomy is the defi nitive treatment for patients 

with acute cholecystitis. Early cholecystectomy performed 

within 2 to 3 days of presentation is preferred over interval 

or delayed cholecystectomy that is performed 6 to 10 

weeks after initial medical therapy. 11,12 About 20% of 

patients fail initial medical therapy and require surgery 

during the initial admission or before the end of the 

planned cooling-off period. 

Laparoscopic cholecystectomy is the preferred 

approach to patients with acute cholecystitis. Conversion 

to an open procedure should be made if the infl ammation 

prevents adequate visualization of important structures. 

The conversion rate to an open cholecystectomy 

is higher (4%-35%) in the setting of acute cholecystitis 

than with chronic cholecystitis. Numerous studies have 

shown the morbidity rate, hospital stay, and time to 

return to work are lower in patients undergoing laparoscopic 

cholecystectomy than open cholecystectomy. 13-15 

Early laparoscopic cholecystectomy, due to a reduced 

length of hospital stay and readmissions, is a more costeffective 

approach than open cholecystectomy for acute 

cholecystitis. 16 Patients who are operated on early in the 

course of their illness (within 48 hours) are more likely 

to have their procedure completed laparoscopically (4% 

versus 23%) than patients with a longer duration of symptoms. 

17 Additional factors predicting the need to convert 

to an open cholecystectomy include increased patient 

age, male gender, elevated American Society of Anesthesiologists 

class, obesity, and thickened gallbladder wall 

(>4 mm). 

Acute cholecystitis may progress to empyema of the 

gallbladder, emphysematous cholecystitis, or perforation 

of the gallbladder despite antibiotic therapy. In each case, 

emergency cholecystectomy is indicated, if the patient


can safely withstand an anesthetic. In most patients, 

cholecystectomy can be performed and is the best treatment 

of complicated acute cholecystitis. Occasionally, the 

infl ammatory process obscures the structures in the triangle 

of Calot, precluding safe dissection and ligation of 

the cystic duct. In these patients, partial cholecystectomy, 

cauterization of the remaining gallbladder mucosa, and 

drainage avoid injury to the common bile duct. In patients 

considered too unstable to tolerate a laparotomy, percutaneous 

transhepatic cholecystostomy under local anesthesia 

can be performed to drain the gallbladder. This 

procedure leaves the gallbladder in place, which may be 

a source of ongoing sepsis. Drainage and IV antibiotics, 

followed by interval laparoscopic cholecystectomy, 

can then be performed after 3 to 4 months to allow 

the patient to recover and the acute infl ammation to 

resolve. 

Choledocholithiasis 

Common bile duct stones are classifi ed by their point of 

origin and are found in 6% to 12% of patients with stones 

in the gallbladder. Most common bile duct stones in 

Western countries form initially in the gallbladder and 

migrate through the cystic duct into the common bile 

duct. These stones are identifi ed as secondary calculi to 

distinguish them from primary common bile duct stones, 

which form within the biliary tract. Common duct stones 

are also defi ned as retained if they are discovered within 

2 years of cholecystectomy, or recurrent if they are 

detected more than 2 years after cholecystectomy. The 

secondary stones are usually of the brown pigment type. 

Identifi cation of brown stones in the common bile duct 

should alert the surgeon to the high likelihood of recurrent 

stones and need for a biliary-enteric drainage procedure. 

The primary stones are associated with biliary 

stasis and infection and are more commonly seen in 

Asian populations. The causes of biliary stasis that lead 

to the development of primary stones include biliary 

stricture, papillary stenosis, tumors, or other (secondary) 

stones. 

Presentation 

Common bile duct stones may be silent and are often 

discovered incidentally. In these patients, biliary obstruction 

is transient, and laboratory tests may be normal. 

About 1% to 2% of patients with normal liver function 

tests managed with laparoscopic cholecystectomy without 

a routine cholangiogram for gallstones present with a 

retained stone after cholecystectomy. 

Clinical features suspicious for biliary obstruction due 

to common bile duct stones include biliary colic, jaundice, 

lightening of the stools, and darkening of the urine. 

In addition, fever and chills may be present in patients 

with choledocholithiasis and cholangitis. Serum bilirubin 

(>3.0 mg/dL), serum aminotransferases, and alkaline 

phosphatase all are commonly elevated in patients with 

biliary obstruction but are neither sensitive nor specifi c 

for the presence of common duct stones. Of these, serum 

bilirubin has the highest positive predictive value (28%- 

50%) for the presence of choledocholithiasis. However, 

laboratory values may be normal in as many as one third 

of patients with choledocholithiasis. 

Diagnosis 

Ultrasonography, commonly the fi rst test, can document 

stones in the gallbladder and estimate the diameter of 

the common bile duct. A dilated bile duct (>8 mm in 

diameter) on ultrasonography in a patient with gallstones, 

jaundice and biliary pain is highly suggestive of choledocholithiasis. 

As stones in the distal bile duct slowly move 

down, bowel gas can preclude their visibility on ultrasound; 

echogenic shadows consistent with calculi in the 

common bile duct are visible in only 60% to 70% of 

patients with choledocholithiasis. Among patients with 

gallstones, the prevalence of choledocholithiasis is signifi 

cantly higher in the setting of a dilated common bile 

duct (diameter >5 mm) than in patients with a nondilated 

duct (58% versus 1%). 18 MRC provides excellent anatomic 

detail, with sensitivity and specifi city of 95% and 98%, 

respectively, for common bile duct stones, avoids the 

need for invasive ERCP in more than 50% of patients and 

can be used as a screening test for patients at low or 

moderate risk for having common duct stones before 

ERCP. 

ERCP is the diagnostic and potentially therapeutic test 

of choice for patients with suspected common bile duct 

stones (Fig. 54-12). Cannulation of the ampulla of Vater 

and diagnostic cholangiography are achieved in more 

than 90% of cases. Minimal morbidity rates of less than 

5% are now achieved in experienced hands and mainly 

consist of cholangitis and pancreatitis. Endoscopic ultrasound 

(EUS) can also be used to identify bile duct stones 

without cannulation of the ampulla and its associated 

risks, but it is less sensitive than ERCP. 

Management 

Endoscopic Cholangiography 

The use of endoscopic cholangiography in patients with 

suspected common bile duct stones not only confi rms 

the diagnosis but also provides ductal clearance of the 

stones and sphincterotomy before subsequent laparoscopic 

cholecystectomy. Endoscopic clearance of stones 

from the common bile duct can avoid the need for an 

open operation if expertise in laparoscopic common bile 

duct exploration is not available. Patients with worsening 

cholangitis, ampullary stone impaction, biliary pancreatitis, 

multiple comorbidities, and cirrhosis are considered 

good candidates for preoperative endoscopic therapy. 

When endoscopic evaluation is carried out routinely in 

all patients, 86% are normal. If clearance is not possible 

because of multiple stones, intrahepatic stones, impacted 

stones, diffi culty with cannulation, duodenal diverticula, 

or biliary stricture, this information is known before 

surgery. Endoscopic sphincterotomy with stone extraction 

is well tolerated in most patients, with a 5% to 8% 

complication rate. Complete clearance of all common 

duct stones is achieved endoscopically in 71% to 75% of 

patients at the fi rst procedure and in 84% to 95% of 

patients after multiple endoscopic procedures. 19

A B 

After endoscopic sphincterotomy and stone extraction, 

patients with gallstones still remain at high risk for developing 

future biliary complications. A signifi cantly greater 

incidence of recurrent biliary symptoms is expected 

among patients managed with a wait-and-see approach 

versus laparoscopic cholecystectomy (47% versus 2%; 

P > .0001) after endoscopic stone extraction. Thirty-seven 

percent of patients managed expectantly later required 

cholecystectomy. 20 Therefore, prompt cholecystectomy 

after endoscopic clearance of the common bile duct 

should be performed during the hospital admission if the 

patient is fi t for surgery. On the other hand, patients older 

than 70 years should have their ductal stones cleared 

endoscopically as their sole therapy; only about 15% 

become symptomatic from their gallbladder stones in 

their remaining lifetime, which can then be treated as 

symptoms arise. 

Laparoscopic Common Bile Duct Exploration 

An intraoperative cholangiogram at the time of cholecystectomy 

will also document the presence of common bile 

duct stones (Fig. 54-13). Laparoscopic common bile duct 

exploration through the cystic duct or with formal choledochotomy 

allows the stones to be retrieved during the 


Figure 54-12 A, MRCP showing multiple, small stones in a nondilated common bile duct. B, Corresponding endoscopic 

retrograde cholangiopancreatography image. (From Moon JH, Cho YD, Cha SW, et al: The detection of 

bile duct stones in suspected biliary pancreatitis: Comparison of MRCP, ERCP, and intraductal US. Am J Gastroenterol 

100:1051-1057, 2005.) 

same procedure. If the expertise and instrumentation for 

laparoscopic common bile duct exploration are not available, 

a drain should be placed and left adjacent next to 

the cystic duct and an endoscopic cholangiogram performed 

the following day. An open common bile duct 

exploration should be performed if endoscopic intervention 

is not available or not feasible because of anatomic 

restrictions or expertise. If a choledochotomy is performed, 

a T tube is left in place. The purpose of the T 

tube is to provide access to the biliary system for postoperative 

radiologic stone extraction. The size of the tube 

is therefore of importance, in that tubes smaller than 16 

French do not allow for postoperative radiologic instrumentation 

without dilation of the tract; a minimum of 4 

to 6 weeks should pass for the tract to mature before 

instrumentation. 

Open Common Bile Duct Exploration 

With the increased use of endoscopic, percutaneous, and 

laparoscopic techniques, open common bile duct exploration 

is rarely performed today. It should be performed 

when a concomitant biliary drainage procedure is indicated. 

Open common bile duct exploration is associated 

with low operative mortality (1%-2%) and operative mor-


Figure 54-13 Intraoperative cholangiogram confi rming the presence 

of common bile duct stones. Calculi are indicated with 

arrows. (Courtesy of Michael D. Holzman, MD.) 

bidity (8%-16%). The rate of retained common bile stones 

using intraoperative choledochoscopy is less than 5%. 

Stones impacted in the ampulla may be diffi cult for both 

endoscopic ductal clearance and common bile duct 

exploration. In these cases, transduodenal sphincteroplasty 

and stone extraction should be performed; 

alternatively, if this is not successful, a choledochoduodenostomy 

or a Roux-en-Y choledochojejunostomy 

should be performed. 

Gallstone Pancreatitis 

Blockage of the pancreatic duct by an impacted stone or 

temporary obstruction by a stone passing through the 

ampulla may lead to pancreatitis by an unknown mechanism. 

An ultrasound in patients with acute pancreatitis of 

uncertain cause is critical to assess for gallstones and 

choledocholithiasis. An ERCP with sphincterotomy and 

stone extraction is the initial treatment and may relieve 

the pancreatitis. Once the pancreatitis has subsided, the 

gallbladder should be removed during the same admission. 

If the pancreatitis is self-limited, the stone has likely 

passed. For these patients, cholecystectomy and an intraoperative 

cholangiogram are indicated. 

Biliary Dyskinesia 

Patients who present with typical symptoms of biliary 

colic but have no evidence of gallstones on ultrasound 

exam should be investigated for biliary dyskinesia. Once 

other possible diagnoses have been excluded with CT 

scan, upper endoscopy, or ERCP, a CCK-Tc-HIDA scan 

should be performed to rule out biliary dyskinesia. CCK 

is infused IV after the gallbladder has been fi lled with 

R. subcostal 

Lateral 

Medial 

Subxiphoid 

Supraumbilical 

Figure 54-14 Trocar placement for laparoscopic cholecystectomy. 

The laparoscope is placed through a 10-mm port just 

above the umbilicus. Additional ports are placed in the epigastrium 

and subcostally in the midclavicular and near the anterior 

axillary lines. (From Cameron J: Atlas of Surgery, vol 2. Philadelphia, 

BC Decker, 1994.) 

the 99m Tc-labeled radionuclide. Twenty minutes after the 

administration of CCK, a gallbladder ejection fraction is 

determined. An ejection fraction less than 35% at 20 

minutes is considered abnormal. 

Patients with symptoms of biliary colic and an abnormal 

gallbladder ejection fraction should be managed 

with a laparoscopic cholecystectomy. Between 85% and 

94% of patients with a low gallbladder ejection fraction 

and symptoms of biliary colic will be asymptomatic or 

improved by cholecystectomy. Commonly, there is histopathologic 

evidence of chronic cholecystitis. 

Sphincter of Oddi Dysfunction 

Pain similar to biliary colic with normal liver function 

tests and episodes of acute pancreatitis have been attributed 

to a poorly defi ned syndrome known as dysfunction 

of the sphincter of Oddi. The pathogenesis is unclear, but 

theories that have been postulated include gallstone 

migration inducing fi brosis of the sphincter, trauma, pancreatitis, 

and congenital anomalies. About 1% of patients 

undergoing cholecystectomy have sphincter of Oddi dysfunction. 

A dilated common bile duct (>12 mm diameter) 

or increase in common bile duct diameter in response to 

CCK is a typical ultrasound fi nding. Delayed emptying of 

contrast medium from the common bile duct after ERCP 

is also indicative of abnormal sphincter function. Ampullary 

manometry indicating an elevated basal sphincter 

pressure (>40 mm Hg) has been correlated with good 

results after treatment that consists of endoscopic or 

operative sphincterotomy. 21

Surgery for Calculous Biliary Disease 

Laparoscopic Cholecystectomy 

Since the introduction of laparoscopic cholecystectomy, 

the number of cholecystectomies performed in the United 

States has increased from about 500,000 per year to 

700,000 per year. Contraindications to laparoscopic cholecystectomy 

include coagulopathy, severe chronic 

obstructive pulmonary disease, end-stage liver disease, 

and congestive heart failure. Currently, the major contraindication 

to completing a laparoscopic cholecystectomy 

is inability to clearly identify all of the anatomic structures. 

The conversion rate for elective laparoscopic 

cholecystectomy should be around 5%, whereas the conversion 

rate in the setting of acute cholecystitis may be 

as high as 30%. Conversion to an open procedure is not 

a failure, and the possibility should be discussed with the 

patient preoperatively. 

Patients undergoing laparoscopic cholecystectomy 

should be prepared and draped in a similar fashion to 

open cholecystectomy. The patient is supine on the operating 

table with the surgeon standing on the patient’s left. 

The pneumoperitoneum is created with carbon dioxide 

gas, either with an open technique or by closed-needle 

technique. With the open technique, a small incision is 

made either above or below the umbilicus into the peritoneal 

cavity. A special blunt-tipped cannula (Hasson) 

with a gas-tight sleeve is inserted into the peritoneal 

cavity and anchored to the fascia. This technique is often 

used following previous abdominal surgery and should 

Right 

subcostal 

lateral 

and medial 

instrument 

positions 

Fundus of 

gallbladder 


avoid infrequent but life-threatening trocar injuries. In the 

closed technique, a special hollow insuffl ation needle 

(Veress) with a retractable cutting sheath is inserted into 

the peritoneal cavity through a periumbilical incision and 

used for insuffl ation. There is no difference in inadvertent 

bowel or tissue injury between the two techniques. 

The laparoscope with the attached video camera is 

then inserted into the umbilical port and the abdomen 

inspected. The additional ports are inserted under direct 

vision (Fig. 54-14). The medial 5-mm cannula is used 

to grasp the gallbladder infundibulum (Fig. 54-15) and 

retract it laterally with the pull toward the right pelvis, to 

expose the triangle of Calot; it is important to widely 

expose the triangle of Calot with this direction of retraction 

to fully enable identifi cation of possible aberrant 

biliary anatomy. This maneuver may require taking down 

the adhesions between the omentum or duodenum and 

the gallbladder. Most of the dissection can be performed 

using a dissector, hook, or scissors. The junction of the 

gallbladder and cystic duct is identifi ed and dissection 

continued until the cystic artery and duct is clearly seen 

entering the gallbladder (Fig. 54-16). A helpful anatomic 

landmark is the cystic lymph node. Careful extended 

dissection of the base of the gallbladder off the liver bed 

is essential to defi ne the duct and artery. The outdated 

infundibular technique of cystic duct dissection and identifi 

cation does not fully expose the triangle of Calot and 

leads to misidentifi cation and is a setup for bile duct 

injury. Partial dissection of the base of the gallbladder off 

the liver bed before dividing either the artery or cystic 

Liver 

Cystic duct 

and 

artery 

Subxiphoid 

instrument 

position 

Figure 54-15 The gallbladder is retracted cephalad using the grasper on the gallbladder fundus and at the infundibulum, 

with the direction of pull toward the right pelvis. The peritoneum overlying the gallbladder infundibulum 

and neck and the cystic duct is divided bluntly, exposing the cystic duct. (From Cameron J: Atlas of Surgery, vol 

2. Philadelphia, BC Becker, 1994.)


Gallbladder 

Cystic artery 

Cystic duct 

Figure 54-16 View obtained after dissection within the triangle of Calot demonstrating the cystic duct and cystic 

artery clearly entering the gallbladder. At this point, it is safe to ligate and divide the cystic duct. Visualization of 

the common bile duct is not necessary. (From Strasberg SM, Hertl M, Soper NJ: An analysis of the problem of 

biliary injury during laparoscopic cholecystectomy. J Am Coll Surg 180:101-125, 1995.) 

duct enables identifi cation of all the anatomy and minimizes 

risk for bile duct injury. 

The next step is ligation of the cystic artery. The artery 

is usually encountered running parallel to and behind the 

cystic duct. Clips are placed proximally and distally on 

the artery, which is then divided. If indicated, an intraoperative 

cholangiogram may now be performed by 

placing a hemoclip proximally on the cystic duct, incising 

the anterior surface of the duct, and passing a cholangiogram 

catheter into the cystic duct. Once the cholangiogram 

is completed, two clips are placed distally on 

the cystic duct, which is then divided. A large cystic duct 

may require placement of a pretied loop ligature or a 

standard suture tied laparoscopically for secure closure. 

Finally, the gallbladder is dissected out of the gallbladder 

fossa with electrocautery. Just before removing the gallbladder 

from the liver, the operative fi eld is carefully 

searched for hemostasis. The gallbladder is then dissected 

off the liver and removed through the umbilical 

port. If the gallbladder is acutely infl amed, gangrenous, 

or entered during the dissection, a plastic specimen 

retrieval bag should be used for removal from the abdominal 

cavity. Any bile or blood that has accumulated should 

be irrigated and sucked away, and if stones were spilled, 

they should be retrieved. Any concern about bile accumulation 

or leak should prompt placement of a closedsuction 

drain through one of the 5-mm ports and left 

underneath the right lobe of the liver close to the gallbladder 

fossa. 

Elective laparoscopic cholecystectomy can be safely 

performed as an outpatient procedure, and most centers 

in the United States have demonstrated a strong trend 

toward ambulatory cholecystectomy. 22 Among patients 

selected for outpatient management, 77% to 97% of 

patients can be successfully discharged without hospital 

admission. 23 

Intraoperative Cholangiogram or Ultrasound 

Use of routine cholangiogram or ultrasound to identify 

so-called silent common bile duct stones is controversial. 

Routine intraoperative cholangiography will detect stones 

in about 7% of patients, outline the anatomy, and identify 

potential biliary injuries, 24 although it does not prevent 

them. A selective intraoperative cholangiogram should be 

performed when the patient has a history of abnormal 

liver function tests, a large duct and small stones, or a 

dilated common bile duct, or if preoperative endoscopic 

cholangiography was not performed in a patient with 

suspected choledocholithiasis (Box 54-4). Laparoscopic 

ultrasonography is as accurate as intraoperative cholangiography 

in detecting common bile duct stones but is 

operator dependent and requires expertise with ultrasound 

and interpretation of results. 25 

Open Cholecystectomy 

Open cholecystectomy has become an uncommon procedure. 

It is now usually performed either as a conversion 

from an attempted laparoscopic cholecystectomy or 

as a second procedure in patients who require laparotomy 

for another reason. It should be performed in any 

patient who cannot tolerate pneumoperitoneum because 

of poor pulmonary or cardiac reserve (Box 54-5). An 

important consideration for open cholecystectomy is in 

patients in whom gallbladder cancer is suspected 

preoperatively. 

From a technical standpoint, open cholecystectomy 

can be performed similarly to the laparoscopic approach. 

After the cystic artery and duct have been identifi ed, the

Box 54-4 Indications for Intraoperative 

Cholangiogram 

Elevated preoperative liver enzymes (AST, ALT, ALP, bilirubin) 

Unclear anatomy during laparoscopic dissection 

Suspicion of intraoperative injury to biliary tract 

Dilated common bile duct on preoperative imaging 

Gallstone pancreatitis without endoscopic clearance of common 

bile duct 

Jaundice 

Large common bile duct and small stones 

Unsuccessful preoperative endoscopic retrograde 

cholangiopancreatography for choledocholithiasis 

gallbladder is dissected from the liver bed, starting with 

the fundus. Alternatively, the retrograde technique can 

be used where the dissection is initiated with the fundus 

and the artery and duct identifi ed, ligated, and divided 

as a fi nal step. It is important to keep the dissection as 

close to the gallbladder as possible, to avoid dissection 

into the liver and subsequent bleeding. The dissection is 

carried proximally toward the cystic artery and the cystic 

duct, which are then ligated and divided. 

Common Bile Duct Exploration 

In patients with large and multiple stones or dilated 

ducts, and when endoscopic therapy fails, laparoscopic 

common bile duct exploration is indicated. If unsuccessful, 

conversion to open surgery is necessary, whereas 

postoperative ERCP should be used as the last resource. 

After intraoperative cholangiogram indicates the presence 

of choledocholithiasis, the surgeon is faced with many 

options. A wide array of techniques and tools are at a 

surgeon’s disposal. The initial step is to determine the 

important factors regarding which modality of treatment 

will best serve the patient. Factors such as diameter and 

anatomy of the cystic and common bile ducts, number 

and size of CBD stones, clinical status of the patient, and 

most importantly, technical skill of the surgeon should 

all be considered. 

Laparoscopic Approach 

If the stones are small, use of saline irrigation through 

the cholangiogram catheter to fl ush the stones into the 

duodenum is all that is necessary. Relaxation of the 

sphincter of Oddi with glucagon may be helpful. If irrigation 

is unsuccessful, a balloon catheter may be passed 

through the cystic duct and down the common bile duct, 

where it is infl ated and withdrawn to retrieve the stones. 

The next attempt should be made with a wire basket 

passed under fl uoroscopic guidance to catch the stones. 

If needed, a fl exible choledochoscope is inserted directly 

into the cystic duct (Fig. 54-17). The cystic duct may have 

to be dilated to allow its passage. Although most authors 

advocate fi rst attempting a transcystic access, there are 

clear indications for a direct common bile duct exploration 

fi rst. The most common scenarios are the presence 

of more than fi ve common bile duct stones, stones larger 

than 9 mm, and common hepatic duct stones. Once in 

the common bile duct, the stones may be caught into 


Box 54-5 Indications for Open Cholecystectomy 

Poor pulmonary or cardiac reserve 

Suspected or known gallbladder cancer 

Cirrhosis and portal hypertension 

Third-trimester pregnancy 

Combined procedure 

a wire basket under direct vision or pushed into the 

duodenum. 

When the duct has been cleared, the cystic duct is 

ligated and cut and the cholecystectomy is completed. If 

the cystic duct cannot be dilated, a longitudinal choledochotomy 

should be made on the anterior wall. After 

adequate dissection, anterior choledochotomy can be 

used. A longitudinal incision is favored because of the 

pattern of terminal arterioles supplying the common bile 

duct. Postoperative biliary drainage with a T tube may 

then be necessary. Clearance of all common bile duct 

stones is achieved in 75% to 95% of cases with laparoscopic 

common bile duct exploration. 19 Many studies 

have shown similar effi cacy of laparoscopic common bile 

duct exploration as endoscopic sphincterotomy and laparoscopic 

cholecystectomy, while demonstrating signifi - 

cant cost analysis in favor of common bile duct exploration 

at one setting. 

Open Approach 

With the increased use of endoscopic, percutaneous, and 

laparoscopic techniques to treat common bile duct stones, 

the open common bile duct exploration is rarely performed 

today. It is now commonly used as a last resort 

if the above therapies fail. The techniques and operative 

manipulations are similar to the laparoscopic approach. 

In patients with a nondilated bile duct (>4 mm), a transduodenal 

sphincterotomy should be performed and the 

duct explored through the sphincteroplasty. This avoids 

the need for a postoperative T tube and the potential for 

a late bile duct stricture. With the use of intraoperative 

choledochoscopy, the rate of retained common bile 

stones is less than 5%. 

Drainage Procedures 

If the stones cannot be cleared or when the duct is very 

dilated (>1.5 cm in diameter), a choledochal drainage 

procedure should be performed. Options for biliary 

drainage include a side-to-side choledochoduodenostomy 

or a choledochojejunostomy with a Roux-en-Y limb 

of jejunum. Surgeon preference dictates which approach 

is used. Use of the duodenum is preferred if the duodenum 

can be fully mobilized (Kocher maneuver) and there 

is minimal scarring. Any concerns about tension should 

prompt use of the jejunum either as an end-to-side or 

side-to-side confi guration. 

Transduodenal Sphincterotomy 

In the current era, endoscopic sphincterotomy has 

replaced open transduodenal sphincterotomy. If an open 

procedure for common bile duct stones is being done in 

which the stones are impacted, recurrent, or multiple, the


A 

B 

Cystic 

duct 

Dilators of 

increasing 

diameter 

Eyepiece Stone basket 

introduced into 

choledochoscope 

5 mm 

Choledochoscope Common 

bile duct 

Papilla 

of Vater 

Stone basket 

engages stone 

Stone 

Ampulla 

of Vater 

Withdrawal 

of basket and 

stone including 

choledochoscope 

Figure 54-17 A, Laparoscopic common bile duct exploration. After dilation of the cystic duct, the fl exible choledochoscope 

is inserted into the abdomen through the small trocar and maneuvered into the distal common bile duct. 

B, A stone basket is passed through the working channel of the choledochoscope and is used to snare a common 

duct stone. The stone basket and choledochoscope are withdrawn together. (From Curet M, Zucker K: Laparoscopic 

surgery of the biliary tract and liver. In Zuidema G [ed]: Shackelford’s Surgery of the Alimentary Tract, 

3rd ed. Philadelphia, WB Saunders, 1996, pp 257-278.)

transduodenal approach may be feasible. The duodenum 

is incised transversely. The sphincter then is incised at 

the 11-o’clock position to avoid injury to the pancreatic 

duct (Fig. 54-18). The impacted stones are removed, as 

are large stones, from the duct. There is no need to fully 

clear the duct of stones because they can now pass 

spontaneously through the cut sphincter. 

Postcholecystectomy Syndromes 

Because of the frequency of laparoscopic cholecystectomy 

being performed today, the surgeon should be 

aware of an entire spectrum of early problems inherent 

to this procedure. Identifi cation and prompt treatment 

are critical for good outcomes (Fig. 54-19). 

Bile Duct Injury and Ligation 

Most benign strictures follow iatrogenic bile duct injury, 

most commonly during laparoscopic cholecystectomy. 

Most injuries are recognized intraoperatively or during 

the early postoperative period, and with appropriate 

management, the long-term results are acceptable. 

Long-term sequelae of unrecognized or inappropriately 

managed biliary strictures may lead to recurrent cholangitis, 

secondary biliary cirrhosis, and portal 

hypertension. 

Pathogenesis 

The incidence of biliary injuries rose sharply in the 1990s 

with the widespread use of laparoscopic cholecystectomy. 

Although the incidence of bile duct injuries during 

open cholecystectomy is only 0.1% to 0.2%, estimates of 

bile duct injuries and leaks after laparoscopic cholecystectomy 

are reported around 0.85% in several large 

studies. 

A number of factors may be involved in the occurrence 

of bile duct injuries during laparoscopic cholecystectomy. 

These include acute or chronic infl ammation, 

obesity, anatomic variations, and bleeding. Surgical technique 

with inadequate exposure and failure to identify 

structures before ligating or dividing them are the most 

common cause of signifi cant biliary injury. The bile duct 

injury rate is increased in patients with complications 

of gallstones, including acute cholecystitis, pancreatitis, 

cholangitis, and obstructive jaundice. Surgeon training 

and experience were recognized as factors in early reports 

of laparoscopic bile duct injuries. As surgeon experience 

increases beyond 20 cases, the bile duct injury rate 

decreases. Recent reports have indicated that errors 

leading to laparoscopic bile duct injuries stem from 

misperception, not errors of skill, knowledge, or judgment. 

The primary cause of error in 97% of cases was a 

visual perceptual illusion, whereas only 3% of injuries 

were due to faults of technical skill. 26 

Aberrant biliary anatomy is often cited as a factor in 

biliary injuries. The bile duct may be narrow and can be 

mistaken for the cystic duct. The cystic duct may travel 

parallel to the common bile duct before joining it, misleading 

the surgeon to the wrong place. Also, the cystic 

duct may enter the right hepatic duct, and the right 

hepatic duct may run aberrantly, coursing through the 


Figure 54-18 A transduodenal sphincterotomy can be used to 

remove distal bile duct stones that may be affected. An incision 

is made enlarging the papilla along the long axis of the duct, and 

the calculus is either expressed or removed using stone forceps. 

(From Zollinger RM Jr, Zollinger RM: Atlas of Surgical Operations, 

7th ed. New York, McGraw Hill, 1993.) 

triangle of Calot and entering the common hepatic duct. 

A number of other technical factors have been implicated 

in biliary injuries. The classic injury occurs when excessive 

cephalad retraction of the gallbladder may align the 

cystic duct with the common bile duct, allowing the latter 

to be mistaken for the cystic duct (Fig. 54-20). Careless 

use of electrocautery may lead to thermal injury. Dissection 

deep into the liver parenchyma may cause injury to 

intrahepatic ducts, and poor clip placement close to the 

hilar area or to structures not well visualized can result 

in a clip across the bile duct. 

The routine use of intraoperative cholangiography to 

prevent bile duct injury is controversial. 24 It may limit the 

extent of injury, but does not seem to prevent it. However, 

if a bile duct injury is suspected during cholecystectomy, 

a cholangiogram must be obtained to identify the 

anatomy. 

Presentation 

Patients with bile duct injuries can present intraoperatively, 

in the early postoperative period, or months or 

years after the initial injury. About 25% of major ductal 

injuries are recognized intraoperatively because of bile 

leakage, an abnormal cholangiogram, or late recognition 

of the anatomy. The most common presentation of a 

complete occlusion of the common hepatic or bile duct


Postcholecystectomy 

pain 

No biloma 

Pain after laparoscopic cholecystectomy 

No jaundice Jaundice 

CT/Ultrasound 

LFTs 

* 

Significant 

postcholecystectomy 

pain 

Biloma 

Biliary leak 

(cystic duct stump leak, 

duct of Luschka leak, 

major ductal injury) 

CT/Ultrasound 

LFTs 

Common bile duct injury 

or stricture 

ERCP 

No biloma 

Retained stone 

Figure 54-19 Workup and diagnostic algorithm of patients with right upper quadrant pain after laparoscopic cholecystectomy. 

CT, computed tomography; ERCP, endoscopic retrograde cholangiopancreatography; LFT, liver 

function test. 

*Signifi cant and persistent pain should by itself necessitate evaluation of the biliary system even if no biloma is 

found. 

Cystic duct 

Common 

bile duct 

Right hepatic 

artery 

Common 

hepatic duct 

Figure 54-20 The classic laparoscopic cholecystectomy bile duct injury. The cystic duct and common bile duct 

are aligned by traction on the gallbladder. A segment of the common bile and hepatic ducts is resected. (From 

Branum G, Schmitt C, Baillie J, et al: Management of major biliary complications after laparoscopic cholecystectomy. 

Ann Surg 217:532-541, 1993.)

is jaundice with or without abdominal pain. Patients 

may also present months or years after prior surgery 

with cholangitis or cirrhosis secondary to a biliary tract 

injury. 

Diagnosis and Management 

The management of bile duct injury is dependent on the 

timing of diagnosis and extent and level of injury. Inappropriate 

management of biliary strictures may result in 

signifi cant morbidity and mortality secondary to complications 

such as biliary cirrhosis or cholangitis. In a 12year 

review of 130 patients with postoperative biliary 

strictures, the causes of mortality were all related to the 

presence of liver parenchymal disease with portal hypertension. 

Twenty-three of these patients had evidence of 

portal hypertension at the time of referral. 27 

Management of the Bile Duct Injury Recognized at the Time 

of Cholecystectomy Isolated, small, non–cautery-based 

partial lateral bile duct injury recognized at time of cholecystectomy 

can be managed with placement of a T 

tube. The T tube can be placed at the site of the injury 

if this is similar in size to a choledochotomy. However, 

if the biliary injury is more extensive, or if there is signifi 

cant thermal damage owing to cautery-based trauma, 

or if the injury involves more than 50% of the circumference 

of the bile duct wall, an end-to-side choledochojejunostomy 

with a Roux-en-Y loop of jejunum should be 

performed. Similarly, major bile duct injuries, including 

transections of the common bile or common hepatic 

duct, can be repaired if recognized at the time of cholecystectomy. 

Isolated hepatic ducts smaller than 3 mm or 

those draining a single hepatic segment can be safely 

ligated. Ducts larger than 3 mm are more likely to drain 

several segments or an entire lobe and need to be reimplanted. 

It cannot be overstated that signifi cant experience 

and judgment are critical to the decision to conduct 

a repair at the time of injury. If one is uncertain or underexperienced, 

and no colleague with suffi cient expertise 

is immediately available, placing a drain followed by 

referral to an experienced center is the most appropriate 

course of action. 

Management of the Bile Duct Injury Recognized After Cholecystectomy 

Most large series report the incidence of ductal 

injury after laparoscopic cholecystectomy to be 0.3% to 

0.85%. Historically, after open cholecystectomy, 10% of 

patients presented within the fi rst week, 70% within 6 

months, and 80% within 1 year. In a recent study of 156 

patients referred for management of biliary strictures 

resulting from bile duct injuries, 9.3% of injuries were 

recognized during laparoscopic versus 0% during open 

cholecystectomy. 28 In this series of 156 patients with 

postoperative biliary strictures, 49 patients (31.4%) presented 

with leaks, 42 (26.9%) presented with jaundice, 

and 50 (32.1%) presented with cholangitis. 28 In general, 

patients with a bile leak will present early, whereas 

patients with postoperative biliary strictures alone often 

present with jaundice or cholangitis months to years after 

the initial injury. 

Diagnosis Abdominal imaging with ultrasonography or 

CT should be performed in patients with signs of abdominal 

pain or peritonitis, sepsis, or any other clinical sus- 


Figure 54-21 Transhepatic cholangiography confi rming ligation 

of the common hepatic duct just distal to the bifurcation 

(arrow). 

picion of biloma. Such patients must be stabilized with 

immediate parenteral antibiotics and image-guided percutaneous 

drainage of any fl uid collections. Patients with 

signs and symptoms of cholangitis should undergo urgent 

cholangiogram with bile duct drainage. Cholangiography 

should be performed to establish the presence of ductal 

stricture, identify the level of the stricture, and identify 

the nature of the injury when necessary. In one study of 

88 patients with bile duct injuries from laparoscopic cholecystectomy, 

attempts at repair were unsuccessful in 27 

of 28 (96%) when preoperative cholangiograms were not 

performed, and 69% unsuccessful when data from cholangiograms 

were incomplete. 29 It is important that the 

method of cholangiography should provide detail of the 

intrahepatic ductal system and the bile duct confl uence. 

Although PTC is the imaging method of choice for most 

postoperative biliary strictures, expertise with this is not 

available at all centers (Fig. 54-21). ERCP may be easier 

to obtain in a patient with a biliary stricture and cholangitis 

who requires urgent cholangiography and biliary 

decompression. However, this is only useful in patients 

with bile duct continuity. Cystic duct leaks or small tangential 

injuries can be treated with endoscopic stenting. 

In situations in which the biliary stricture is too tight to 

pass with ERCP, PTC may be performed for proximal 

biliary decompression. 

CT arteriography should be considered in the preoperative 

evaluation of patients with benign biliary


Partial injury 

(30%) to CBD 

Cautery injury 

Intraoperative 

cholangiogram 

Roux-en-Y 

choledochojejunostomy 

strictures. Unrecognized injury to the hepatic artery or a 

portal vein branch occurs with a frequency of 12% to 

47% concomitant with a bile duct injury. Certainly, if 

signifi cant bleeding required urgent control at the time 

of the original operation, a vascular injury should 

be considered. However, the clinical consequences of 

hepatic artery injury are not fully known, but at least one 

study suggested that the presence of a right hepatic artery 

disruption should not affect the surgical repair of a bile 

duct injury. 30,31 In patients presenting with late strictures 

with evidence of liver dysfunction, a CT arteriogram 

should be performed to evaluate for evidence of portal 

hypertension. 

Intraoperative Considerations 

The management of postoperative biliary strictures following 

ductal injury depends on the degree of injury, the 

presence of stricture-induced complications, and the 

operative risk of the patient. After recognition of a bile 

duct injury or stricture, a multidisciplinary team consisting 

of experienced interventional radiologists, endoscopists, 

and surgeons, coordinated by an experienced hepatobiliary 

surgeon, should plan the following specifi c goals: 

1. Control the infection (abscess or cholangitis) 

2. Drain the biloma 

3. Complete the cholangiography 

4. Provide defi nitive therapy with controlled reconstruction 

or stenting (Fig. 54-22) 

These goals do not mandate elaborate workup and 

delayed repair in all cases. Initial experience suggested 

that immediate repair of bile duct injury from cholecystectomy 

can give good results with low morbidity when 

performed properly; more recent data, however, suggest 

Complete transection 

of CBD 

>3 mm 

in size 

Injury to isolated 

hepatic duct 

Reimplantation or 

reconstruct with Roux-en-Y 

hepaticojejunostomy 

An adequate incision permitting full visualization is 

necessary for a good biliary-enteric anastomosis. A right 

subcostal incision extended to either the midline (hockey 

stick) or the left (chevron incision) is usually necessary. 

The liver should be completely freed from the diaphragm, 

and adhesions from previous operations should be taken 

down to facilitate creation of a Roux-en-Y jejunal limb if 

necessary (Fig. 54-23). The Hepp-Couinaud approach to 

bile duct reconstruction is the best option in most circumstances. 

This technique requires dissection of the 

hilar plate to expose the left hepatic duct and allow for 

a side-to-side anastomosis of the left hepatic duct to the 

Roux-en-Y jejunal limb. The use of a Roux-en-Y jejunal 

limb is favored over a direct choledochoduodenostomy 

or choledochojejunostomy because it also allows for the 

creation of an “access loop” of the proximal portion of 

the Roux-en-Y limb for future interventional radiologic 

access. 

Interventional Radiologic and Endoscopic Techniques 

Interventional radiologic techniques are useful in patients 

with bile duct injuries, leaks, or postoperative strictures. 

These techniques allow percutaneous drainage of abdominal 

fl uid collections, preoperative identifi cation of the 

ductal anatomy through percutaneous transhepatic cholangiography, 

and stricture dilation with or without placement 

of palliative stents for bile drainage in the patient 

whose overall physiologic status precludes a major operation. 

Percutaneous transhepatic dilation can be employed 

in patients with intrahepatic ductal disease and in patients 

in whom ERCP is not possible. It is often used as an 

adjunct to operative repair in order to assist with identifi 

cation of the proximal biliary tree for reconstruction and 

for the dilation of anastomotic strictures. 

The success rate of percutaneous transhepatic dilation 

is reported between 50% and 70%. Patients with anastomotic 

strictures (including biliary-enteric anastomotic 

strictures) have the highest success rates. A study of 89 

patients treated for major bile duct injuries following 

laparoscopic cholecystectomy showed that by a mean 

follow-up of 27 months, percutaneous dilation yielded 

only a 64% success rate in ischemic strictures versus 92% 

at 33.4 months in patients with biliary-enteric anastomotic 

strictures. 33 In addition, although mortality following percutaneous 

dilation is low, complication rates are reported 

as high as 35%, and complications consist mainly of 

hemobilia, cholangitis, and bile leaks. These procedures 

often require multiple sessions of dilation to achieve 

long-term success rates. 

When reported from large-volume centers, endoscopic 

and percutaneous methods of dilation have equivalent 

effi cacy. Endoscopic dilation of benign extrahepatic 

biliary strictures is also a useful adjunctive option in 

patents with a dominant extrahepatic stricture causing 

clinical symptoms. In general, treatment of biliary strictures 

with this technique, as with interventional radiologic 

methods, requires multiple sessions of dilations, and 

nonischemic strictures (anastomotic strictures) respond 

best. Endoscopic dilation also has a low mortality rate, 

but it has a signifi cant morbidity rate. The more common 

complications following endoscopic biliary interventions 


Figure 54-23 End-to-side biliary reconstruction with Roux-en-Y 

hepaticojejunostomy. Note than anterior row of PDS sutures is 

placed fi rst to elevate anterior wall of bile duct and facilitate 

exposure. 

include hemobilia, bile leak, pancreatitis, and cholangitis. 

In a study of 101 patients with benign biliary strictures, 

66 patients were treated endoscopically, with a reported 

re-stricture rate of 18% at 3 months and a complication 

rate of 35%. 34 Although endoscopic and interventional 

radiologic procedures are not ideal long-term treatments 

for unresponsive biliary strictures, endoscopic stenting 

and drainage is a successful treatment option for cystic 

duct leak or small common bile duct leaks following 

laparoscopic cholecystectomy. 

Careful long-term follow-up of patients with biliary 

strictures treated with percutaneous or endoscopic dilation 

methods is required because ischemic biliary strictures 

will not respond permanently to dilation. Early 

retreatment (through repeat dilation or biliary-enteric reconstruction) 

of postdilation recurrent strictures is essential 

to prevent secondary biliary cirrhosis. The risk for additive 

morbidity from the required repeat sessions and the 

risk for late stricture recurrence should be considered and 

discussed with patients when treatment options for 

benign biliary strictures are being considered. 

Outcomes 

Acceptable long-term results can be achieved in most 

patients undergoing operative repair of bile duct injuries. 

More than 90% of patients are free of jaundice and cholangitis 

after operative repair of a laparoscopic bile duct 

injury. 28 The best results are obtained when the injury is 

recognized during the cholecystectomy and repaired by 

an experienced biliary surgeon. Postoperative injuries 

identifi ed in the presence of concomitant biliary leak 

should be repaired once the biliary leak has subsided 

and tissue planes are less infl amed, usually 6 weeks after 

initial laparoscopic cholecystectomy. Complications of


biliary reconstruction can be managed nonoperatively, 

and mortality rates have been less than 1%. 32 Common 

complications include recurrent cholangitis, external 

biliary fi stula, bile leak, and hemobilia. Restenosis of 

a biliary-enteric anastomosis occurs in about 10% of 

patients, and may manifest up to 20 years later. About 

two thirds of recurrent strictures become symptomatic 

within 2 years after repair. The more proximal strictures 

are associated with a lower success rate than are distal 

ones. Percutaneous balloon dilation with stenting has a 

signifi cantly lower success rate (64%) than operative 

repair. Although most patients are free of jaundice and 

cholangitis after operative repair of a bile duct injury, 

there appears to be a signifi cant impact of the injury on 

the quality of life. 35 

Postcholecystectomy Pain 

Abdominal pain or other symptoms originally attributed 

to the gallbladder may persist or recur months or years 

after cholecystectomy. Improvements in imaging have 

decreased the incidence of this pain, which was once 

reported to be as high as 20%. Patients presenting with 

right upper quadrant pain, jaundice, and chills shortly 

after cholecystectomy should be evaluated for retained 

stones or biliary leak. Other causes of abdominal pain in 

patients with normal liver function tests should also be 

investigated. Another possibility in a small number of 

patients with persistent pain following cholecystectomy 

is abnormalities in the sphincter of Oddi such as stenosing 

papillitis or sphincter dysfunction. 

Retained Biliary Stones 

Retained or recurrent stones following cholecystectomy 

present soon after (

A 

Recurrent Pyogenic Cholangitis 

Cholangiohepatitis or intrahepatic stones are endemic in 

East Asia. It is uncommon in North America except in 

the Chinese population. It is more common in people 

with poor economic status and living standards. The 

infectious aspect of this disease is caused by bacterial 

contamination, usually biliary pathogens, and biliary parasites, 

such as Clonorchis sinensis, Opisthorchis viverrini, 

and Ascaris lumbricoides. Biliary sludge and dead bacterial 

cell bodies form brown pigment stones formed 

throughout the biliary tree, which cause partial obstruction. 

Biliary strictures and repeated episodes of cholangitis 

are the common clinical course and may lead to 

hepatic abscesses and cirrhosis. Patients are at risk for 

cholangiocarcinoma due to persistent biliary infection 

and irritation from stones and sludge. 

Presentation 

Patients with recurrent pyogenic cholangitis (RPC) commonly 

present with frequent episodes of pain, fever, and 

jaundice. MRC and PTC are the primary imaging modalities 

for monitoring of disease progression (Fig. 54-25). 

They are useful for identifying location and severity of 


Figure 54-24 A posteroanterior radiograph obtained during a barium examination of the small bowel shows an 

irregular collection of barium in the right upper quadrant (A, arrowheads), representing partial fi lling of the cystic 

duct. Both jejunum and ileum are markedly dilated, with dilution of the barium in a pattern consistent with small 

bowel obstruction. There is abrupt termination of the barium column at the site of an oval intraluminal fi lling 

defect (A, arrow). A view of the end of the barium column shows luminal obstruction by a smooth intraluminal 

mass (B, arrows) with faint calcifi cation of the peripheral rim. Exploratory laparotomy revealed a foreign body in 

the terminal ileum that was 4 cm by 4 cm and felt hard. (From Kaiser AM, Molmenti EP: Gallstone ileus. N Engl 

J Med 335:942, 1996.) 

B 

stones and strictures and allow decompression of the 

biliary tree in a septic patient. 

Management 

Patients with RPC should be treated with a multidisciplinary 

approach including endoscopists, interventional 

radiologists, and surgeons because of the frequency and 

inaccessibility of strictures and stones. The long-term goal 

of therapy is to extract stones, remove debris, and relieve 

strictures. Because clearance of all stones at any one 

operation is diffi cult, Roux-en-Y hepaticojejunostomy 

with a subcutaneous afferent limb (Hudson loop) is a 

safe and effective way to provide access to the biliary 

tree for stone extractions. 36 Cholangiocarcinoma has been 

reported in 1% to 10% of patients with RPC; therefore, 

patients with adequate hepatic reserve and a dominant 

lobe with stones should undergo extended hepatectomy 

of the involved side, Roux-en-Y hepaticojejunostomy, 

and Hudson loop. This would remove the stones and 

reduce the future risk for cholangiocarcinoma. About 50% 

of patients require further percutaneous choledochoscopy 

or balloon dilation to clear any remaining stones or 

manage persistent strictures.


Figure 54-25 Endoscopic retrograde cholangiopancreatography 

of patient with recurrent pyogenic cholangitis. Note the presence 

of intrahepatic stone and stricturing of the bile ducts. 

Noncalculous Biliary Disease 

Acute Acalculous Cholecystitis 

Acute infl ammation of the gallbladder can occur without 

gallstones. Acute acalculous cholecystitis accounts for 5% 

to 10% of all patients with acute cholecystitis and is the 

diagnosis in about 1% to 2% of patients undergoing cholecystectomy. 

It has a more fulminant course than acute 

calculous cholecystitis and more commonly progresses 

to gangrene, empyema, or perforation. Acute acalculous 

cholecystitis occurs most frequently in elderly and critically 

ill patients after trauma, burns, long-term parenteral 

nutrition, and major operations such as abdominal aneurysm 

repair and cardiopulmonary bypass. Although the 

exact etiology is unclear, gallbladder stasis and ischemia 

have been implicated as causative factors. Stasis is 

common in critically ill patients not being fed enterally 

and may lead to colonization of the gallbladder with 

bacteria. Visceral ischemia is also common in patients 

with acute acalculous cholecystitis and may explain the 

high incidence of gallbladder gangrene. 

The signs and symptoms of acute acalculous cholecystitis 

parallel acute calculous cholecystitis. Patients may 

also present with only unexplained fever, leukocytosis, 

and hyperamylasemia without right upper quadrant tenderness. 

If untreated, rapid progression to gangrene and 

perforation may occur. 37 Radiologic fi ndings are also 

similar except for the absence of gallstones. Ultrasonography 

is the diagnostic test of choice, especially because 

it can be done at the bedside. Cholescintigraphy demonstrates 

absent gallbladder fi lling, but the false-positive 

rate may be as high as 40%. 

Emergency cholecystectomy is the appropriate treatment 

for acute acalculous cholecystitis for patients who 

are stable enough to tolerate the anesthetic and procedure. 

Because of the high incidence of gangrene, perforation, 

and empyema, open cholecystectomy is often the 

preferred approach. Because most patients are critically 

ill, the morbidity rate of acute acalculous cholecystitis in 

recent series is 40%. If patients are unfi t for surgery, 

percutaneous, ultrasound-guided, or CT-guided cholecystostomy 

is the treatment of choice. If the diagnosis is 

uncertain, percutaneous cholecystostomy can be both 

diagnostic and therapeutic. About 90% of patients will 

improve with percutaneous cholecystostomy. 

Acute Cholangitis 

Cholangitis is an ascending bacterial infection of the 

biliary ductal system with obstruction most commonly 

due to choledochal stones. Although cultures of the gallbladder 

and bile ducts are usually sterile, in the presence 

of common bile duct stones or other obstructing pathology, 

the incidence of positive bile cultures increases. The 

most common organisms present in the bile in patients 

with cholangitis include E. coli, Klebsiella pneumoniae, 

Streptococcus faecalis, and Bacteroides fragilis. Even in 

the presence of high bacteria counts, clinical cholangitis 

and bacteremia do not develop unless obstruction causes 

elevated intraductal pressures. Although stones are the 

most common cause of obstruction in cholangitis, other 

etiologies include benign and malignant strictures, anastomotic 

strictures, cholangiocarcinoma, and periampullary 

cancer. 

Diagnosis 

Cholangitis may be either self-limited or toxic with severe 

illness, including jaundice, fever, abdominal pain, mental 

status changes, and hypotension (Reynold’s pentad). 

Fever and chills are the most common presentation and 

are due to cholangiovenous and cholangiolymphatic 

refl ux. Normal biliary pressures range from 7 to 14 cm 

H 2O; in the presence of bactibilia and normal biliary 

pressures, hepatic vein blood and perihepatic lymph are 

sterile. However, with partial or complete biliary obstruction, 

intrabiliary pressures rise to 18 to 20 cm H 2O, and 

organisms rapidly appear in both the blood and lymph. 

The most common causes of biliary obstruction are 

choledocholithiasis, benign strictures, biliary-enteric anastomotic 

strictures, and cholangiocarcinoma and periampullary 

cancer. Before 1980, choledocholithiasis was the 

cause of about 80% of the reported cases of cholangitis, 

but in recent years, malignant strictures have become a 

more frequent cause in tertiary referral centers. Leukocytosis, 

hyperbilirubinemia, and elevations of alkaline phosphatase 

and transaminases all are common in patients with 

cholangitis. Although ultrasound, CT, and MRI may be 

helpful in identifying the cause of obstruction, cholangiography 

is mandatory as a diagnostic and potentially therapeutic 

intervention. If ERCP is not available, PTC should 

be performed. Cholangiography will identify the level of 

and reason for obstruction, allow for culture and possible 

biopsy if a mass is present, and provide drainage of the 

bile ducts with stents, catheters, or dilation.

Management 

IV antibiotics and aggressive hydration are the initial 

treatment in patients with acute cholangitis. Identifying 

severity of ascending cholangitis is crucial to the diagnostic 

and therapeutic management of the patient (Fig. 

54-26). Patients in septic shock with toxic cholangitis may 

require intensive care unit monitoring and vasopressors 

to support blood pressure. Most patients will respond to 

these measures alone. However, in 15% of cases, urgent 

biliary decompression will be necessary. Biliary decompression 

may be performed endoscopically or by a percutaneous 

transhepatic route based on the level of the 

obstruction. Patients with a proximal hilar obstruction or 

a biliary-enteric anastomotic stricture should be drained 

transhepatically. Choledocholithiasis or suspected ampullary 

tumors are best accessed endoscopically. If ERCP or 

PTC is not possible, an emergent operation and decompression 

of the common bile duct with a T tube should 

be performed. Defi nitive operative therapy should be 

deferred until the cholangitis has been treated, the patient 

stabilized, and the diagnosis confi rmed. 

Overall, the mortality rate associated with an episode 

of gallstone cholangitis is about 2%, but is much higher 

in patients with toxic cholangitis (5%). Renal failure, 

hepatic abscess, and malignancy are all associated with 

Ascending cholangitis 

Acute, but not toxic Toxic 

IV antibiotic and 

IV hydration 

Ultrasound 

Stone disease Ductal dilation, 

suspect mass 

ERCP or 

LAP 

Cholecystectomy 

with IOC 

CT/MRCP 

Resuscitation and stabilization 

IV antibiotic and IV hydration 

Urgent decompression 

Proximal obstruction Distal obstruction 

PTC Unsuccessful ERCP 

Unsuccessful 

decompression 

Operative 

decompression 


Successful 

decompression 

Figure 54-26 Diagnostic and therapeutic algorithm of patients with ascending cholangitis. CT, computed tomography; 

ERCP, endoscopic retrograde cholangiopancreatography; IOC, intraoperative cholangiogram; LAP, laparoscopic; 

MRCP; magnetic resonance cholangiopancreatography; PTC, percutaneous transhepatic cholangiography. 

higher morbidity and mortality. Hepatic abscess is frequently 

observed in patients with biliary pathology and 

should be considered in patients who do not respond to 

therapy. 

Primary Sclerosing Cholangitis 

Primary sclerosing cholangitis (PSC) is a cholestatic liver 

disease characterized by fi brotic strictures involving the 

intrahepatic and extrahepatic biliary tree in the absence 

of a known precipitating cause (Fig. 54-27). Some patients 

remain asymptomatic for years, whereas others rapidly 

progress to bile duct loss, cirrhosis, and liver failure. 

Genetic and immunologic factors appear to have a role 

in the pathogenesis of this disease. It is more common 

in certain HLA haplotypes such as B8/DR3. 

The diseases with the strongest association with PSC 

are infl ammatory bowel disease and primarily ulcerative 

colitis. The incidence of ulcerative colitis in patients with 

PSC ranges from 60% to 72%. Patients with PSC are at 

increased risk for developing cholangiocarcinoma. The 

risk for developing cholangiocarcinoma is 1% per year 

in patients with PSC. Between 10% and 15% of patients 

undergoing liver transplantation as treatment of PSC will 

have an unsuspected cholangiocarcinoma on explant 

analysis.


Figure 54-27 MRC documenting diffuse biliary strictures characteristic 

of primary sclerosing cholangitis. 


There are no pathognomonic signs of PSC, and the 

natural history is variable. Although patients can be 

asymptomatic for up to 15 years, prolonged disease ultimately 

leads to progressive hepatic failure. Mean age at 

presentation is 40 to 45 years, and most patients are 

male. 38 About 75% of patients are symptomatic at presentation 

with evidence of cholestatic liver disease such as 

jaundice, pruritus, and fatigue. Symptoms of bacterial 

cholangitis are uncommon. The condition is characterized 

by relapses and remissions, with quiescent periods. 

The median survival for patients with PSC from the time 

of diagnosis ranges from 10 to 12 years. 

Diagnosis 

Cholangiography confi rms the diagnosis of PSC with 

evidence of diffuse multifocal strictures commonly found 

in both intrahepatic and extrahepatic bile ducts. Involvement 

of the extrahepatic ducts alone without intrahepatic 

duct involvement occurs in 5% to 10% of patients with 

PSC. Despite the presence of diffuse disease in most 

patients with PSC, the hepatic duct bifurcation is often 

the most severely strictured segment of the biliary tree. 

A liver biopsy to determine the degree of hepatic fi brosis 

or the presence of cirrhosis is also critical in selecting 

therapy. 

Management 

Primary sclerosing cholangitis is a progressive disease 

that eventually results in biliary cirrhosis. Patients with 

persistent biliary sepsis, biliary cirrhosis, and manifestations 

of end-stage liver disease (ascites, variceal bleeding) 

are best treated with liver transplantation. Five-year graft 

and patient survival after transplantation are excellent 

Figure 54-28 MRC demonstrating anastomotic stricture (arrow) 

following right lobe living donor liver transplantation. Note the 

slight dilation of the biliary tree proximal to the stricture and 

signifi cant dilation distal. 

at 72% and 85%, respectively. Recurrent PSC has been 

reported in up to 10% of patients and may require 

retransplantation. 

An important consideration in the management of PSC 

is the risk for superimposed cholangiocarcinoma, which 

occurs in 10% to 20% of cases. 39 Rapid onset of jaundice, 

pruritus, and weight loss may be clues to the diagnosis 

of cholangiocarcinoma but are not specifi c. Cancer 

antigen (CA) 19-9 may be helpful if levels are greater 

than 100 U/mL but is not predictive. Repeated brushings 

for cytology by endoscopic or percutaneous approaches 

should be employed to distinguish benign from malignant 

dominant strictures. Long-term survival in patients 

with a small incidental cholangiocarcinoma (

Box 54-6 Todani Modifi cation of Alonso-Lej 

Classifi cation of Choledochal Cysts 

Type I: Dilation of the extrahepatic biliary tree. Type I dilations 

are further classifi ed according to the shape of the affected 

segment into type Ia: cystic dilation; type Ib: focal segmental 

dilation; type Ic, fusiform dilation. 

Type II: Diverticular dilation of the extrahepatic biliary tree 

Type III: Cystic dilation of the intraduodenal portion of the 

common bile duct (choledochocele) 

Type IVa: Dilation of the extrahepatic and intrahepatic biliary 

tree 

Type IVb: Dilation of multiple sections of the extrahepatic bile 

ducts 

Type V: Dilation confi ned to the intrahepatic bile ducts (Caroli’s 

disease) 

Data from Todani T, Watanabe Y, Narusue M, et al: Congenital bile duct 

cysts: Classifi cation, operative procedures, and review of thirty-seven cases 

including cancer arising from choledochal cyst. Am J Surg 134:263-269, 

1977. 

surgery is limited. These patients are not common, 

however, because bilateral involvement is the usual presentation. 

Resection of the extrahepatic biliary tree with 

bilateral hepaticojejunostomies may have a role in patients 

without cirrhosis or signifi cant fi brosis on biopsy, but 

timing, aggressiveness, and selection remain unclear. 

Limited data have shown that overall survival has been 

signifi cantly longer in noncirrhotic patients treated with 

resection than in patients managed nonoperatively. 38 

Liver transplantation has produced excellent results in 

patients with PSC and end-stage liver disease, with a 5year 

actuarial patient survival rate of 72% and a 5-year 

graft survival rate of 72% reported. 

Biliary Strictures 

Benign bile duct strictures have numerous causes, including 

chronic pancreatitis, common bile duct stones, acute 

cholangitis, biliary obstruction due to cholecystolithiasis 

(Mirizzi’s syndrome), PSC, RPC, post-transplantation strictures, 

and biliary-enteric anastomosis. Patients most commonly 

present with episodes of cholangitis or jaundice. 

Cholangiography provides diagnostic and therapeutic 

information regarding location, severity, and causes of 

biliary strictures. Percutaneous or endoscopic dilation 

and stent placement give good results in more than half 

of patients. Surgery with Roux-en-Y choledochojejunostomy 

or hepaticojejunostomy is the standard of care with 

excellent results in 80% to 90% of cases. 28 

Anastomotic biliary strictures after liver transplantation 

or biliary-enteric bypass can usually be managed nonoperatively 

(Fig. 54-28). Percutaneous transhepatic stents 

are required for patients with Roux-en-Y reconstruction 

because of diffi culty accessing the papilla. This provides 

symptomatic relief but may not provide long-term success. 

Biliary strictures after duct-to-duct reconstruction are best 

treated with endoscopic stenting initially, and if unsuccessful, 

then Roux-en-Y biliary-enteric reconstruction. 

I 


II III 

IVa IVb V 

Figure 54-29 Todani modifi cation of Alonso-Lej classifi cation of 

choledochal cysts. (From Chijiiwa K, Koga A: Surgical management 

and long-term follow-up of patients with choledochal 

cysts. Am J Surg 165:238-242, 1993.) 

Biliary Cysts 

Cystic dilation of the biliary ducts, also known as a choledochal 

cyst, is an uncommon but serious condition that 

requires surgical treatment. Although choledochal cysts 

frequently present in infancy and childhood, the disease 

is more commonly diagnosed in adults. The incidence of 

choledochal cysts is only between 1 in 100,000 and 1 in 

150,000 people in Western countries but is much more 

common in Japan. They occur three to eight times more 

commonly in women. This congenital disorder involves 

isolated or combined dilation of the extrahepatic or intrahepatic 

biliary tree. 

Pathogenesis 

The most commonly accepted theory is an anomalous 

pancreatic duct–biliary duct junction (APBDJ). A high 

common bile duct–pancreatic duct junction creates a long 

common channel. This results in refl ux of pancreatic fl uid 

into the distal common hepatic duct and results in 

mucosal injury, chronic infl ammation, and weakening of 

the bile duct wall. This proposed mechanism is supported 

by elevated levels of amylase in choledochal 

cysts. 

In 1977, Todani modifi ed the Alonso-Lej classifi cation 

(Box 54-6 and Fig. 54-29) and combined the extrahepatic 

and intrahepatic types into a classifi cation that is currently 

used by most surgeons. Type I cysts are the most common 

and make up 50% of choledochal cysts. 


The classic clinical triad associated with choledochal cysts 

includes right upper quadrant pain, jaundice, and an


abdominal mass. Only 10% of patients present with this 

triad. Adults have a slightly different presentation (abdominal 

pain and jaundice) than children because of a higher 

incidence of bile calculi or sludge and pancreatic-biliary 

ductal malformation. 

Severe hepatobiliary complications may result from 

long-standing biliary cysts if left untreated. Portal hypertension 

may develop as a result of portal vein compression 

by the adjacent cyst or cirrhosis secondary to 

long-term biliary obstruction. Some patients may present 

with variceal hemorrhage as an initial manifestation. Very 

rarely, patients may present with bilious ascites and peritonitis 

as a result of rupture of a choledochal cyst, and 

pseudocysts may appear surrounding the common bile 

duct. Those patients also have a high incidence of developing 

sludge, cholelithiasis, or choledocholithiasis and 

have commonly had a prior cholecystectomy. 

The incidence of carcinoma (bile duct, hepatic, or 

gallbladder in origin) in the choledochal cyst ranges from 

2.5% to 26%, which is well above the rate of less than 

1% for the general population. Many patients have biliary 

cancer at the time of initial presentation. Chronic infl ammation 

caused by bile stagnation has been suggested as 

a possible mechanism for the development of cancer by 

causing metaplasia of the epithelium of the cystic wall. 

Laboratory evaluation may demonstrate liver dysfunction 

in 60% of adult patients but is not specifi c. The 

diagnosis can be established with ultrasound or CT scan 

(Fig. 54-30A). Cholangiography is required to determine 

the type of choledochal cyst and plan operative treatment 

(see Fig. 54-30B). ERCP is more useful in defi ning the 

distal ductal anatomy and the presence of APBDJ, whereas 

PTC is useful in defi ning the proximal ductal anatomy 

and the presence of intrahepatic disease. 

Management 

The goals of management are to relieve symptoms and 

prevent long-term complications of biliary cysts such as 

cholangitis, portal hypertension, cirrhosis, and potential 

carcinoma. Cholecystectomy, resection of the extrahepatic 

biliary tract including the choledochal cyst, with 

Roux-en-Y hepaticojejunostomy is the appropriate treatment 

for type I and II choledochal cysts. The goal of cyst 

excision is to completely remove the lining mucosa of 

the bile duct cysts (Fig. 54-31), with oversewing of the 

distal duct. Simple enteric drainage (choledochocystojejunosotomy) 

of the bile duct cyst is associated with recurrent 

biliary stasis and infection 24 and does not prevent 

development of biliary malignancy. Todani and colleagues 

have reported a 10-year mean interval between 

internal drainage and detection of carcinoma. 41 Cholangiocarcinoma 

is uncommon in children with choledochal 

cysts, but the risk in adults may be as high as 30%. Resection 

of the extrahepatic cyst is also recommended for 

type IV cysts; if the intrahepatic cysts are confi ned to one 

side of the liver, hepatic resection of the involved liver 

is recommended. With long-standing Caroli’s disease 

(Fig. 54-32), hepatic parenchymal damage may ensue 

from diffuse biliary dilation and periportal fi brosis and 

eventually result in cirrhosis and liver failure. Liver trans- 

A 

B 

Figure 54-30 A, Computed tomography scan demonstrating type 

I choledochal cyst. B, Endoscopic retrograde cholangiopancreatography 

visualizing anatomy and relationship to nearby structures 

of choledochal cyst is important in operative planning. 

(From Shah SA, Alsoufi B, Callery MP: Bile duct cysts. Available 

online: http://www.unboundsurgery.com.) 

plantation offers a potential cure without long-term complications 

of recurrences of Caroli’s disease. 

Polyploid Lesions of the Gallbladder 

Benign masses classifi ed as polyploid lesions of the gallbladder 

include benign pseudotumors, such as cholesterol 

polyps and adenomyomatosis, and adenomas, and 

appear in 3% to 7% of normal subjects undergoing 

abdominal ultrasound and in 2% to 12% of cholecystectomy 

specimens. Cholesterol polyps are the most common

Figure 54-31 Operative photography demonstrating neck of 

biliary cyst during excision of a type I choledochal cyst. 

Figure 54-32 Computed tomography demonstrating Caroli’s 

disease. 

benign masses of the gallbladder and are usually smaller 

than 10 mm, have a characteristic echogenic pedunculated 

appearance on ultrasound, and are often multiple 

(30% of cases). Adenomyomatosis appears as a sessile 

polyp with characteristic microcysts on ultrasound and is 

often larger than 10 mm. Adenoma may be diffi cult to 

distinguish from adenocarcinoma of the gallbladder; the 

main differentiating feature is a lack of transmural invasion 

on ultrasound, which is sometimes diffi cult to accurately 

assess. Risk factors associated with malignancy are 

age older than 60 years, coexistence of gallstones, a 

documented increase in size, and size larger than 10 mm. 

All patients with symptomatic polyploid lesions of the 


gallbladder should undergo laparoscopic cholecystectomy. 

Any patient with risk factors or a suspicion of in 

situ or frank adenocarcinoma should undergo open cholecystectomy. 

Lesions smaller than 10 mm that are asymptomatic 

and without ultrasound features of neoplasia may 

be safely observed with follow-up imaging. 

Benign Biliary Masses 

The most common benign tumor of the extrahepatic 

biliary tree is the papilloma or adenoma, which arises 

from the glandular epithelium lining the ducts. Most of 

these tumors are found in or close to the ampulla (47%). 

Jaundice is the presenting symptom in most patients but 

can also be accompanied by right upper quadrant pain. 

A benign adenomatous tumor should be included in the 

differential in all secondary operations performed for 

obstruction of the biliary system. It is a soft lesion, is 

diffi cult to palpate, and presents very little resistance to 

ductal probes. Treatment should consist of total resection 

of symptomatic lesions with some duct wall as well. High 

recurrence rates have been reported after simple curettage 

of the polyps. Lesions situated at the ampulla can 

usually be managed by transduodenal papillotomy or 

wide local excision. 

Benign infl ammatory tumors of the bile duct, known 

as pseudotumors and benign fi brosing disease can mimic 

biliary tract tumors. Their histology consists of only 

infl ammatory cells and fi brosis. Pseudotumors appear to 

occur most frequently above the biliary bifurcation but 

are still usually extrahepatic. About 10% of resected cholangiocarcinomas 

are pseudotumors in origin. 

MALIGNANT BILIARY DISEASE 

Gallbladder Cancer 

Cancer of the gallbladder is an aggressive malignancy 

that occurs predominantly in elderly people. Besides the 

exceptional cases detected incidentally at the time of 

cholecystectomy for gallstone disease, which are usually 

early stage, the prognosis for most patients is poor. Series 

from the Western hemisphere have reported 5-year survival 

rates of only 5% to 38%. 42-44 Unfortunately, many of 

these tumors are unresectable at presentation, and most 

must be managed nonoperatively. Recently, an aggressive 

surgical approach for patients with localized gallbladder 

cancer has produced encouraging results with an 

acceptable morbidity. 

Incidence 

Gallbladder cancer is the fi fth most common gastrointestinal 

malignancy, with about 5000 new cases diagnosed 

annually in the United States. Cancer of the gallbladder 

is two to three times more common in women than men, 

in part because of the higher incidence of gallstones in 

women. More than 75% of patients with this malignancy 

are older than 65 years. The incidence of gallbladder 

cancer varies considerably with both ethnic background 

and geographic location. In the United States, gallbladder 

cancer is more common in Native Americans. Similarly,


Box 54-7 Risk Factors for Gallbladder Carcinoma 

Gallstones 

Porcelain gallbladder 

Anomalous pancreatobiliary junction 

Choledochal cysts 

Adenomatous gallbladder polyps 

Primary sclerosing cholangitis 

Obesity 

Salmonella typhi infection 

in Chile, the incidence of gallbladder cancer is particularly 

high. 

Etiology 

Several factors have been associated with an increased 

risk for developing gallbladder cancer (Box 54-7). 

Although not entirely clear, the pathogenesis is likely 

related to chronic infl ammation. Among these factors, 

gallstones are the most common because of the high 

prevalence in the general population. The association 

between an APBDJ, a porcelain gallbladder, and other 

biliary disorders such as choledochal cysts and primary 

sclerosing cholangitis and gallbladder cancer has been 

recognized more recently. 

A strong association has long been noted between 

gallbladder cancer and cholelithiasis, which is present in 

75% to 90% of cases. The incidence of gallstones increases 

with age, and by age 75, about 35% of women and 20% 

of men in the United States have developed gallstones. 

The incidence of gallbladder cancer is about seven times 

more common in the presence of cholelithiasis and 

chronic cholecystitis than in people without gallstones. 

In addition, the risk for developing gallbladder cancer is 

higher in patients with symptomatic gallstones than in 

patients with asymptomatic gallstones. About 1% of all 

elective cholecystectomies performed for cholelithiasis 

harbor an occult gallbladder cancer. 

Pathology and Staging 

Ninety percent of cancers of the gallbladder are classifi ed 

as adenocarcinoma. Squamous cell, oat cell, undifferentiated, 

and adenosquamous cancers and carcinoid tumors 

are much less frequent. Six percent of gallbladder adenocarcinomas 

demonstrate papillary features histopathologically; 

these tumors are commonly diagnosed while 

localized to the gallbladder and are also associated with 

an improved overall survival. At diagnosis, 25% of cancers 

are localized to the gallbladder wall, 35% have associated 

metastases to regional lymph nodes or extension into 

adjacent organs, and 40% have already metastasized to 

distant sites. 

Lymphatic drainage from the gallbladder occurs in a 

predictable fashion and correlates with the pattern of 

lymph node metastases seen in gallbladder cancer. 

Hepatic involvement with gallbladder cancer can occur 

by direct invasion through the gallbladder bed, angiolymphatic 

portal tract invasion, or distant hematogenous 

Table 54-2 TNM Staging for Gallbladder Cancer 

T1 Tumor invades lamina propria (T1a) or 

muscular (T1b) layer 

T2 Tumor invades perimuscular connective tissue, 

no extension beyond the serosa or into the 

liver 

T3 Tumor perforates the serosa (visceral 

peritoneum) and/or directly invades into liver 

and/or one other adjacent organ or structure 

such as the stomach, duodenum, colon, 

pancreas, omentum, or extrahepatic bile ducts 

T4 Tumor invades main portal vein or hepatic 

artery or invades multiple extrahepatic organs 

and/or structures 

N0 No lymph node metastases 

N1 Regional lymph node metastases 

M0 No distant metastases 

M1 Distant metastases 

Stage Stage Grouping 

IA T1 N0 M0 

IB T2 N0 M0 

IIA T3 N0 M0 

IIB T1 N1 M0 

T2 N1 M0 

T3 N1 M0 

III T4 Any N M0 

IV Any T Any N M1 

Adapted from Greene F, Page D, Fleming I, et al (eds): AJCC Cancer 

Staging Manual, 6th ed. New York, Springer-Verlag, 2002. 

spread. The current TNM classifi cation of the American 

Joint Committee on Cancer (AJCC) is shown in Table 

54-2. The appropriate management and overall prognosis 

are strongly dependent on tumor stage. 


Gallbladder cancer most often presents with right upper 

quadrant abdominal pain often mimicking cholecystitis 

and cholelithiasis. Weight loss, jaundice, and an abdominal 

mass are less common presenting symptoms. About 

40% of patients present with symptoms of chronic cholecystitis, 

often with a recent change in the quality or 

frequency of the painful episodes. Another common presentation 

is similar to acute cholecystitis, with a short 

duration of pain associated with vomiting, fever, and 

tenderness. Signs and symptoms of malignant biliary 

obstruction with jaundice, weight loss, and right upper 

quadrant pain are also common. Patients can also present 

with symptoms of a nonbiliary malignancy with anorexia 

and weight loss in the absence of jaundice or, least commonly, 

with signs of gastrointestinal bleeding or obstruction. 

Gallbladder cancer is often misdiagnosed as chronic 

cholecystitis, pancreatic cancer, acute cholecystitis, choledocholithiasis, 

or gallbladder hydrops. 

Diagnosis 

Ultrasonography is often the fi rst diagnostic modality 

used in the evaluation of patients with right upper quad-

ant abdominal pain. A heterogeneous mass replacing the 

gallbladder lumen and an irregular gallbladder wall are 

common sonographic features of gallbladder cancer. The 

sensitivity of ultrasound in the detection of gallbladder 

cancer ranges from 70% to 100%. CT scan usually demonstrates 

a mass replacing the gallbladder or extending 

into adjacent organs. Spiral CT also demonstrates the 

adjacent vascular anatomy. With newer magnetic resonance 

techniques, gallbladder cancers may be differentiated 

from the adjacent liver and biliary obstruction or 

encasement of the portal vein may also be easily 

visualized. 

Cholangiography also may be helpful in diagnosing 

jaundiced patients with gallbladder cancer. The typical 

cholangiographic fi nding in gallbladder cancer is a long 

stricture of the common hepatic duct. Angiography, spiral 

CT, or MRI may identify encasement of the portal vein 

or hepatic artery. If radiographic studies suggest that the 

tumor is unresectable (liver or peritoneal metastases, 

portal vein encasement, or extensive hepatic invasion), 

a biopsy of the tumor is warranted and can be performed 

under ultrasound or CT guidance. 

Management 

The appropriate operative procedure for the patient with 

localized gallbladder cancer is determined by the pathologic 

stage. Patients with tumors confi ned to the gallbladder 

mucosa or submucosa (T1a) or confi ned to the 

gallbladder muscularis (T1b) are usually identifi ed after 

cholecystectomy for gallstone disease and have an overall 

5-year survival rate approaching 100% and 85%, respectively. 

Therefore, cholecystectomy is adequate therapy 

for patients with T1 tumors. Recurrent cancer at port sites 

and peritoneal carcinomatosis have been reported after 

laparoscopic cholecystectomy, even for patients with in 

situ disease; therefore, all port sites should be excised if 

a patient has had a previous laparoscopic cholecystectomy. 

Bile spillage occurs in 26% to 36% of laparoscopic 

cholecystectomies and appears to be even more common 

(50%) in cases of gallbladder cancer. Spillage is associated 

with poor survival even in early stage (T1 and T2) 

gallbladder cancer. Patients with preoperatively suspected 

gallbladder cancer should undergo open cholecystectomy 

to minimize the chance of bile spillage and tumor 

dissemination. 

Cancer of the gallbladder with invasion beyond (stages 

II and III) the gallbladder muscularis is associated with 

an increased incidence of regional lymph node metastases 

and should be managed with an “extended cholecystectomy.” 

This includes lymphadenectomy of the cystic 

duct, pericholedochal, portal, right celiac, and posterior 

pancreatoduodenal lymph nodes. Obtaining an R0 resection 

should be the goal of surgery and results in an 

improved survival compared with patients who have 

remaining microscopic or macroscopic disease. 42 Adequate 

clearance of the pericholedochal lymph nodes may 

be facilitated by resection of the common bile duct, but 

common duct resection is not always necessary; in those 

cases in which the cystic duct stump margin is positive 

for malignancy, common duct resection with Roux-en-Y 

reconstruction is mandatory. Extension into the hepatic 


parenchyma is common, and extended cholecystectomy 

should incorporate at least a 2-cm margin beyond the 

palpable or sonographic extent of the tumor. For smaller 

tumors, this goal can be achieved with a wedge resection 

of the liver. For larger tumors, an anatomic liver resection 

(extended right hepatectomy) may be required to achieve 

a histologically negative margin. Staging laparoscopy 

should be performed in patients with gallbladder cancer, 

as a high proportion (50%-55%) of patients have hepatic 

or extrahepatic disease that is not detected by noninvasive 

staging modalities. 

In most cases, therapy for gallbladder cancer is palliative. 

If a tissue diagnosis can be established in patients 

with an unresectable tumor, nonoperative palliation 

should be considered. Many of these patients have 

obstructive jaundice that can be managed with either an 

endoscopic or percutaneously placed biliary stent. Pain 

is another problem that should be treated aggressively to 

improve quality of life. Percutaneous celiac ganglion 

nerve block may reduce the need for narcotics. 

The results of chemotherapy in the treatment of 

patients with gallbladder cancer have been quite poor. 

External-beam and intraoperative radiation therapy have 

both been used in the management of patients with 

gallbladder cancer. Unfortunately, no randomized data 

have demonstrated improved survival with either chemotherapy 

or radiation. 

Survival 

Survival in patients with gallbladder cancer is strongly 

infl uenced by the pathologic stage at presentation. Recent 

advances in surgical technique and aggressiveness of 

resection for gallbladder cancer have resulted in improved 

overall survival 42 (Fig. 54-33). Patients with cancer limited 

to the gallbladder mucosa and lamina propria (T1a) have 

an excellent prognosis. Invasion into the muscular wall 

(T1b) of the gallbladder increases the risk for recurrent 

cancer after curative resection. However, no difference 

% Alive 

100 

75 

50 

25 

0 

P < .03 

0 

20 

40 

60 

Survival (months) 

80 

TP 2 

TP 1 

100 

Figure 54-33 Improved survival due to an aggressive approach 

to gallbladder cancer comparing two time periods (TPs), 1990- 

1996 and 1996-2002 (circles) (P < .03). (From Dixon E, Vollmer 

CM, Sahajpal A, et al: An aggressive surgical approach leads to 

improved survival in patients with gallbladder cancer: A 12-year 

study at a North American Center. Ann Surg 241:385-394, 

2005.)


Survival 

1.0 

0.8 

0.6 

0.4 

0.2 

0.0 

0 12 24 36 48 60 

Months 

Figure 54-34 Survival following surgical resection for T2 gallbladder 

cancer. Patients undergoing radical resection (triangles) are 

compared with patients undergoing simple cholecystectomy 

(circles) (P > .05). (From Fong Y, Jarnigan W, Blumgart LH: 

Gallbladder cancer: Comparison of patients presenting initially 

for defi nitive operation with those presenting after prior noncurative 

intervention. Ann Surg 232:557-569, 2000.) 

in 10-year survival has been demonstrated after simple 

cholecystectomy (100%) and extended cholecystectomy 

(75%) among patients with T1b gallbladder cancer. Invasion 

into the subserosa (T2) increases the risk for regional 

lymph node metastases to between 33% and 50%. Fiveyear 

survival in patients with T2 tumors is improved following 

extended cholecystectomy with lymphadenectomy 

and liver resection (59%-61%) compared with simple 

cholecystectomy (17%-19%) 43 (Fig. 54-34). Several groups 

have recently reported 5-year overall survival rates for 

resected patients with stages IIA and IIB gallbladder 

cancer of 28% to 63% and 19% to 25%, respectively. 

However, most patients with gallbladder cancer have 

advanced unresectable disease at the time of presentation. 

As a result, fewer than 15% of all patients with 

gallbladder cancer are alive after 5 years. The median 

survival for stage IV patients at the time of presentation 

is only 1 to 3 months. 

Bile Duct Cancer 

Cholangiocarcinoma is an uncommon tumor that may 

occur anywhere along the intrahepatic or extrahepatic 

biliary tree. These tumors are located most commonly at 

the hepatic duct bifurcation (60%-80% of cases). Less 

commonly, tumors originate in the distal common bile 

duct or in the intrahepatic bile ducts. Most cholangiocarcinomas 

present with jaundice, and the diagnosis 

of cholangiocarcinoma should be considered in every 

patient with obstructive jaundice. When possible, surgical 

resection does offer a chance for long-term disease-free 

survival. Many patients, however, will be candidates only 

for palliative bypass or operative or nonoperative intubation 

aimed to provide biliary drainage and prevent cholangitis 

and hepatic failure. 

Incidence 

The reported incidence of cholangiocarcinoma in the 

United States is 1 or 2 cases per 100,000 population. 

Incidence data from the American Cancer Society are 

diffi cult to interpret because intrahepatic bile duct cancers 

are included with primary liver cancers, whereas extrahepatic 

biliary cancers are in a separate category that 

includes gallbladder cancer. In the United States, an estimated 

17,550 primary liver cancers will be diagnosed in 

2005. Data from the National Cancer Institute Surveillance, 

Epidemiology, and End Results (SEER) program 

suggest that about 15% of these (2600 cases) will be 

intrahepatic cholangiocarcinomas. About 7000 cases of 

extrahepatic bile duct cancer are diagnosed annually in 

the United States, two thirds of which are gallbladder 

cancers. Thus, 2000 to 3000 cases per year are extrahepatic 

cholangiocarcinomas. 

For unclear reasons, the incidence of intrahepatic cholangiocarcinoma 

has been rising over the past 2 decades 

in Europe and North America, Asia, Japan, and Australia, 

whereas rates of extrahepatic cholangiocarcinoma are 

declining internationally. The rising rates of intrahepatic 

cholangiocarcinoma have not been associated with an 

increase in the proportion of early-stage or smaller 

lesions. Furthermore, incidence rates do not appear to 

have reached a plateau. 

Risk Factors 

A number of diseases have been linked to cholangiocarcinoma, 

including primary sclerosing cholangitis, choledochal 

cysts, and hepatolithiasis. Characteristics common 

to these diseases include bile duct stones, biliary stasis, 

and infection. Bile duct cancers in patients with primary 

sclerosing cholangitis are most often extrahepatic, commonly 

occur near the hepatic duct bifurcation, and are 

diffi cult to differentiate from the multiple, benign strictures 

associated with this disease. As a general rule, the 

incidence of biliary tract cancers increases with age; the 

typical patient with cholangiocarcinoma is between 50 

and 70 years of age. However, patients with PSC and 

those with choledochal cysts present nearly 2 decades 

earlier. In contrast to gallbladder cancer, for which female 

gender predominates, the incidence of cholangiocarcinoma 

is slightly higher in men. This probably refl ects the 

higher incidence of PSC in men. Hepatolithiasis is also a 

defi nite risk factor for cholangiocarcinoma, which will 

develop in 5% to 10% of patients with intrahepatic stones. 

Hepatitis B and C are also now recognized as risk factors 

in the development of intrahepatic cholangiocarcinoma. 

At least two genetic disorders are associated with an 

increased risk for cholangiocarcinoma: the inherited 

“cancer family” syndrome termed Lynch syndrome II, and 

a rare inherited disorder called multiple biliary papillomatosis; 

the latter condition is characterized by multiple 

adenomatous polyps in the bile ducts, and repeated 

episodes of abdominal pain, jaundice, and acute 

cholangitis. 

Prior biliary-enteric anastomosis may also increase 

the future risk for cholangiocarcinoma. Five percent of 

patients in a large Italian series developed cholangiocar-

Figure 54-35 Bismuth classifi cation of perihilar cholangiocarcinoma 

by anatomic extent. Type I tumors (upper, left) are confi 

ned to the common hepatic duct, and type II tumors (upper, 

right) involve the bifurcation without involvement of secondary 

intrahepatic ducts. Type IIIa and IIIb tumors (lower, left) extend 

into either the right or left secondary intrahepatic ducts, respectively. 

Type IV tumors (lower, right) involve the secondary intrahepatic 

ducts on both sides. 

cinoma between 11 and 18 years after a biliary-enteric 

anastomosis. The risk for bile duct cancer was higher 

after transduodenal sphincteroplasty and choledochoduodenostomy 

than after hepaticojejunostomy and was 

most strongly associated with recurrent episodes of cholangitis. 

Multiple other risk factors for cholangiocarcinoma 

have been identifi ed, including liver fl ukes, Thorotrast, 

industrial chemicals, dietary nitrosamines, and exposure 

to dioxin. 

Staging and Classifi cation 

Cholangiocarcinoma is best classifi ed anatomically into 

three broad groups: 

1. Intrahepatic 

2. Perihilar 

3. Distal 

Intrahepatic tumors are treated like hepatocellular 

carcinoma with hepatectomy, when possible. The 

perihilar tumors make up the largest group and are 

managed with resection of the bile duct, preferably 

with hepatic resection. Distal tumors are managed in a 

fashion similar to other periampullary malignancies with 

pancreatoduodenectomy. 

Cancers of the hepatic duct bifurcation have also been 

classifi ed according to their anatomic location (Fig. 

54-35). In this system, type I tumors are confi ned to the 

common hepatic duct, and type II tumors involve the 

bifurcation without involvement of secondary intrahe- 


Table 54-3 Current American Joint Commission on Cancer 

TNM Staging System for Cholangiocarcinoma 

Stage 0 Tis N0 M0 

Stage I T1 N0 M0 

Stage II T2 N0 M0 

Stage III T1 or T2 N1 or N2 M0 

Stage IVA T3 Any N M0 

Stage IVB Any T Any N M1 

Tis, carcinoma in situ; T1, tumor invades the subepithelial connective 

tissue; T2, tumor invades perifi bromuscular connective tissue; T3, tumor 

invades adjacent organs. 

N0, no regional lymph node metastases; N1, metastasis to 

hepatoduodenal ligament lymph nodes; N2, metastasis to peripancreatic, 

periduodenal, periportal, celiac, and/or superior mesenteric artery lymph 

nodes. 

M0, no distant metastasis; M1, distant metastasis. 

Adapted from Greene F, Page D, Fleming I, et al (eds): AJCC Cancer 

Staging Manual, 6th ed. New York, Springer-Verlag, 2002. 

patic ducts. Types IIIa and IIIb tumors extend into either 

the right or left secondary intrahepatic ducts, respectively, 

and type IV tumors involve the secondary intrahepatic 

ducts on both sides. 

Cholangiocarcinoma is also staged according to the 

tumor, node, metastasis (TNM) classifi cation of the AJCC 

(Table 54-3). Using this system, stage IA tumors are 

limited to the bile duct, whereas stage IB tumors invade 

periductal tissues. Stage IIA tumors are locally advanced 

without lymph node metastases, and stage IIB tumors 

have regional lymph node metastases. Stage III tumors 

are locally advanced and unresectable, and stage IV 

tumors have distant metastases. Portal vein involvement 

and lobar atrophy have been reported as important prognostic 

factors for cholangiocarcinoma and may be incorporated 

in the classifi cation in the future. 45 


More than 90% of patients with perihilar or distal tumors 

present with jaundice. Patients with intrahepatic cholangiocarcinoma 

are rarely jaundiced until late in the course 

of the disease. Less common presenting clinical features 

include pruritus, fever, mild abdominal pain, fatigue, 

anorexia, and weight loss. Cholangitis is not a frequent 

presenting fi nding but most commonly develops after 

biliary manipulation. Except for jaundice, the physical 

examination is usually normal in patients with 

cholangiocarcinoma. 

Diagnosis and Assessment of Resectability 

At the time of presentation, most patients with perihilar 

and distal cholangiocarcinoma have a total serum bilirubin 

level greater than 10 mg/dL. Marked elevations in 

alkaline phosphatase are also routinely observed. Serum 

CA 19-9 may also be elevated in patients with cholangiocarcinoma, 

although levels may fall once biliary obstruction 

is relieved. 

The radiologic evaluation of patients with cholangiocarcinoma 

should delineate the overall extent of the


Figure 54-36 Computed tomography scan visualizes mass at 

hepatic duct bifurcation (arrow) resulting in bilateral biliary 

dilation and extensive perihilar malignancy. 

tumor, including involvement of the bile ducts, liver, hilar 

vessels, and distant metastases. The initial radiographic 

studies consist of either abdominal ultrasound or CT 

scanning (Fig. 54-36). Intrahepatic cholangiocarcinomas 

are easily visualized on CT scans; however, perihilar and 

distal tumors are often diffi cult to visualize on ultrasound 

and standard CT scan. Cholangiocarcinoma can be 

enhanced by using delayed-phase CT acquisition (10 

minutes after contrast injection). A hilar cholangiocarcinoma 

gives a picture of a dilated intrahepatic biliary tree 

and a normal or collapsed gallbladder and extrahepatic 

biliary tree. Distal tumors lead to dilation of the gallbladder 

and both the intrahepatic and extrahepatic biliary 

tree. 

After documentation of bile duct dilation, biliary 

anatomy has been traditionally defi ned cholangiographically 

through either the percutaneous transhepatic or the 

endoscopic retrograde route. The most proximal extent 

of the tumor is the most important feature in determining 

resectability in patients with perihilar tumors, and the 

percutaneous route is favored in these patients because 

it defi nes the proximal extent of tumor involvement most 

reliably. PET will detect unsuspected distant or intrahepatic 

metastases in up to 30% of patients with cholangiocarcinoma. 

MRC offers good resolution of both the 

intrahepatic and extrahepatic biliary tree, but should be 

substituted with PTC or ERCP in patients that will require 

preoperative or palliative biliary drainage. Biliary drainage 

is necessary if the patient’s bilirubin is more than 

10 mg/dL, but it has been associated with an increased 

risk for cholangitis and longer postoperative hospital stay 

in patients with obstructive jaundice who then undergo 

resection. 46 Cholestasis, biliary cirrhosis, and liver dys- 

Box 54-8 Radiologic Criteria to Suggest 

Unresectability of Cholangiocarcinoma 

Bilateral hepatic duct involvement up to secondary radicals 

Bilateral hepatic artery involvement 

Encasement of the portal vein proximal to its bifurcation 

Atrophy of one hepatic lobe with contralateral portal vein 

encasement 

Atrophy of one hepatic lobe with contralateral biliary radical 

involvement 

Distant metastasis 

Adapted from Anderson CD, Pinson CW, Berlin J, Chari RS: Diagnosis 

and treatment of cholangiocarcinoma. Oncologist 9:43-57, 2004. 

function develop rapidly in the face of unrelieved biliary 

obstruction. 

Percutaneous fi ne-needle aspiration biopsy, brush and 

scrape biopsy, and cytologic examination of bile all have 

been used to establish a tissue diagnosis; however, the 

sensitivity in detecting a malignancy is low, and a benign 

result should be considered unreliable. Seven to 15% of 

patients with preoperative symptoms and imaging studies 

and intraoperative fi ndings consistent with malignant 

biliary obstruction will ultimately have benign lesions on 

histologic analysis of resection specimens. 

Management 

Hepatic lobar atrophy and hepatic ductal extension 

predict the need for hepatectomy in order to achieve a 

margin-negative resection. 45,47 All available data must be 

used to distinguish resectability from unresectability (Fig. 

54-37). Radiographic criteria that suggest unresectability 

of perihilar tumors include bilateral hepatic duct involvement 

up to secondary radicals, encasement or occlusion 

of the portal vein proximal to its bifurcation, atrophy of 

one liver lobe with encasement of the contralateral portal 

vein branch, involvement of bilateral hepatic arteries, or 

atrophy of one liver lobe with contralateral secondary 

biliary radical involvement (Box 54-8). Ipsilateral portal 

vein involvement and involvement of secondary biliary 

radicals do not preclude resection, nor does ipsilateral 

lobar atrophy. 48 Curative treatment of patients with cholangiocarcinoma 

is possible only with complete resection 

(R0). 

Patients with unequivocal evidence of unresectable 

cholangiocarcinoma at initial evaluation are palliated 

nonoperatively. Nonoperative palliation can be achieved 

both endoscopically and percutaneously. Percutaneous 

biliary drainage has several advantages over endoscopic 

management in patients with perihilar cholangiocarcinoma, 

whereas endoscopic palliation is the preferred 

approach in patients with distal cholangiocarcinoma. 

More recently, metallic stents have been used to palliate 

patients with malignant biliary obstruction. These stents 

remain patent longer than plastic stents and require fewer 

subsequent manipulations. 

Operative Approach 

Surgical exploration should be undertaken in good-risk 

patients without evidence of metastatic or locally unre-

sectable disease; however, intraoperatively, more than 

half of these patients are found to have either peritoneal 

or hepatic metastases or, more likely, locally unresectable 

disease. Selective use of laparoscopy in patients with 

locally advanced but potentially resectable perihilar cholangiocarcinoma 

may avoid laparotomy in some patients 

with metastatic disease. In patients who are found to 

have extensive metastatic disease, the preoperatively 

placed biliary stents should be left in place. However, a 

cholecystectomy should be performed to avoid the risk 

of acute cholecystitis, which occurs in patients with longterm 

indwelling biliary stents. In patients with locally 

advanced unresectable perihilar tumors, several operative 

approaches are available for palliation, including a 

Roux-en-Y hepaticojejunostomy to segment III or V. 

Distal cholangiocarcinoma—Distal lesions are 

usually treated with pancreaticoduodenectomy 

(Whipple’s procedure). A pylorus-preserving 


Figure 54-37 Flow chart depicting the workup and treatment of a patient with suspected hilar cholangiocarcinoma. 

CT, computed tomography; ERCP, endoscopic retrograde cholangiopancreatography; MRCP; magnetic resonance 

cholangiopancreatography; PTC, percutaneous transhepatic cholangiography. (From Anderson CD, Pinson CW, 

Berlin J, Chari RS: Diagnosis and treatment of cholangiocarcinoma. Oncologist 9:43-57, 2004.) 

operation is preferable and feasible in most 

patients, with 5-year survival rates averaging 15% 

to 25%, but can be as high as 54% in selected 

patients who undergo complete resection for 

node-negative disease. If resection is not possible 

owing to vascular encasement, cholecystectomy, 

Roux-en-Y hepaticojejunostomy proximal to the 

tumor, and a gastrojejunostomy to prevent gastric 

outlet obstruction should be performed. 

Intrahepatic cholangiocarcinoma—Intrahepatic 

cholangiocarcinoma is treated by hepatic 

resection, and outcomes depend on disease stage 

(particularly the status of the lymph nodes) and 

the ability to achieve negative margins. There is a 

broad range of long-term outcomes in patients 

undergoing complete resection (3-year survival 

rates of 22%-66%). 

Perihilar cholangiocarcinoma—For perihilar 

cholangiocarcinomas, bile duct resection alone


leads to high local recurrence rates due to early 

involvement of the confl uence of the hepatic 

ducts and the caudate lobe branches. The addition 

of a modifi ed hepatic resection has improved 

resectability rates. However, curative resections are 

still possible in less than half of patients, and most 

do not achieve long-term disease control. Surgical 

treatment depends on the Bismuth-Corlette 

classifi cation (see Fig. 54-35). For type I and II 

lesions, the procedure is en bloc resection of the 

extrahepatic bile ducts and gallbladder with 5- to 

10-mm bile duct margins, and regional 

lymphadenectomy with Roux-en-Y 

hepaticojejunostomy. In addition to the above 

operations, type II tumors may require hepatic 

lobectomy. Because type II and III lesions often 

involve the ducts of the caudate lobe, many 

surgeons recommend routine caudate lobectomy. 

Type III and IV tumors are amenable to 

potentially curative resection in centers with 

expertise in these procedures. Aggressive 

techniques such as hepatectomy and portal vein 

resection to achieve negative margins are now 

routine in specialized centers. 

Substantial progress has been made in curative resection 

for perihilar cholangiocarcinomas. At least some of 

this progress has been attributed to the routine use of 

partial hepatectomy. The rate of margin-negative resections 

is consistently more than 75% when partial hepatectomy 

(including resection of the caudate lobe) is 

added to the bile duct resection. This aggressive approach 

has resulted in 5-year survival rates above 50% in some 

series. However, these improvements have been accompanied 

by higher surgical mortality rates (8%-10% versus 

2%-4%). The major prognostic factors are margin status 

and tumor stage. In addition to location, stage, and status 

of the resection margins, other factors infl uence outcome 

after resection. 

Medical Therapy 

Numerous reports have suggested that radiation therapy 

improves survival for patients with cholangiocarcinoma, 

especially when resection is impossible. External-beam 

radiotherapy has been delivered using a variety of innovative 

techniques, including intraoperative radiotherapy 

and brachytherapy with iridium-192 through percutaneous 

or endoscopic stents. However, no prospective, randomized 

trials have been reported, and a well-controlled, 

but not randomized, trial reported no benefi t for postoperative 

adjuvant radiation. A survival benefi t for postoperative 

radiation therapy may be limited to patients with 

local extension into the liver parenchyma and microscopic 

residual disease following resection. Chemotherapy 

has also not been shown to improve survival in 

patients with either resected or unresected cholangiocarcinoma. 

Given the potential radiosensitization effect of 

5-fl uorouracil or gemcitabine, the combination of radiation 

and chemotherapy may be more effective than either 

agent alone. As with gallbladder cancer, the role of adju- 

vant chemoradiation needs to be tested in patients with 

cholangiocarcinoma. Finally, photodynamic therapy is 

emerging as an important palliative option for patients 

with unresectable cholangiocarcinoma, although it is not 

widely available. 

Outcomes 

Long-term survival in patients with cholangiocarcinoma 

is highly dependent on the stage of disease at presentation 

and on whether the patient is treated by a palliative 

procedure or complete tumor resection. The rate of 

margin-negative resections has consistently been reported 

above 75% when partial hepatectomy including resection 

of the caudate lobe is added to the biliary resection. 49,50 

This aggressive approach has increased 5-year survival 

rates to above 50% in some series. 47,49 However, the perioperative 

mortality rates accompanying these more 

extensive resections are slightly higher than those accompanying 

local excision only (8%-10% versus 2%-4%). 49,51,52 

Patients with resectable distal bile duct cancer have the 

highest rate of resection. Those with resectable distal bile 

duct cancer have a median survival of 32 to 38 months 

and a 5-year survival rate of 28% to 45%. Even with 

multimodality adjuvant therapy, median survival for unresectable 

intrahepatic tumors has been only 6 to 7 months. 

Similarly, median survival for patients with unresectable 

perihilar tumors varies between 5 and 8 months. 

The use of liver transplantation for the treatment of 

cholangiocarcinoma is controversial and should be 

reserved for select patients as a part of research protocols. 

As more effective adjuvant and neoadjuvant protocols 

are developed, transplantation may be a more useful 

treatment for this disease. As indicated previously, this is 

suggested by early reports from the Mayo Clinic in which 

survival after neoadjuvant chemoradiation and liver transplantation 

was signifi cantly improved over resection 

alone for stage I and II hilar cholangiocarcinoma. 40 

Metastatic and Other Tumors 

Hepatocellular carcinoma and liver metastases can cause 

obstructive jaundice by direct extension into the perihilar 

bile ducts. Hepatocellular and metastatic colorectal carcinoma 

have also both been reported to “embolize” into 

the biliary tree. This rare phenomenon occurs when 

tumor cells are shed into the biliary tract and implant 

distally, leading to biliary obstruction when the tumor 

embolus increases in size. Hepatic cystadenomas and 

cystadenocarcinomas arise from the biliary epithelium, 

and these tumors or the mucin they produce may also 

cause bile duct obstruction. 

Primary and secondary hepatic tumors can also 

produce biliary obstruction by metastasizing to hilar or 

pericholedochal lymph nodes. Hepatocellular carcinoma, 

colorectal carcinoma, and pancreatic carcinoma are the 

most common primary sites associated with biliary tract 

obstruction from lymph node metastases, although nodal 

metastases from a number of tumors including breast and 

ovarian cancer have been reported to cause bile duct 

obstruction. Lymphoma can also result in biliary obstruc-

tion and mimic either pancreatic cancer or perihilar 

cholangiocarcinoma. Although commonly extensive, lymphomas 

usually respond to chemotherapy, leading to 

resolution of the biliary obstruction. 

Selected References 

Anderson CD, Pinson CW, Berlin J, et al: Diagnosis and treatment 

of cholangiocarcinoma. Oncologist 9:43-57, 2004. 

Excellent review and summary of the modern treatment of 

cholangiocarcinoma. 

Boerma D, Rauws EA, Keulemans YC, et al: Wait-and-see policy 

or laparoscopic cholecystectomy after endoscopic sphincterotomy 

for bile-duct stones: A randomised trial. Lancet 360:761- 

765, 2002. 

A randomized, prospective trial comparing observation versus laparoscopic 

cholecystectomy following endoscopic removal of stones. Recurrent 

biliary symptoms developed in 47% in the observation arm, and 

one third of these required cholecystectomy. 

Cotton PB: Endoscopic management of bile duct stones (apples 

and oranges). Gut 25:587, 1984. 

This classic article describes problems and results of the endoscopic 

management of choledocholithiasis. 

Dixon E, Vollmer CM Jr, Sahajpal A, et al: An aggressive surgical 

approach leads to improved survival in patients with gallbladder 

cancer: A 12-year study at a North American Center. Ann 

Surg 241:385-394, 2005. 

A review of the results in a single center over 12 years indicating that 

an aggressive approach to gallbladder cancer with extensive resection 

improves long-term survival. 

Glenn F: Acute cholecystitis. Surg Gynecol Obstet 143:56, 

1976. 

This is a classic review with more than 200 cases by the late master 

biliary tract surgeon. Serious risk factors and the increased mortality in 

elderly patients are stressed. 

Nakeeb A, Comuzzie AG, Martin L, et al: Gallstones: Genetics 

versus environment. Ann Surg 235:842-849, 2002. 

An excellent study that examines the contribution of genetics to the 

pathogenesis of symptomatic gallstones. 

Rea DJ, Heimbach JK, Rosen CB, et al: Liver transplantation 

with neoadjuvant chemoradiation is more effective than resection 

for hilar cholangiocarcinoma. Ann Surg 242:451-458, 

2005. 

Pivotal paper in the renewed interest in liver transplantation in the 

management of cholangiocarcinoma. 

Reisner RM: Gallstone ileus: A review of 1001 reported cases. 

Am Surg 60:441, 1994. 

An exhaustive review of all cases reported in the English language from 

1953 to 1993. It covers all aspects of epidemiology, diagnosis, therapy, 

and complications. 

Southern Surgeons Club: A prospective analysis of 1518 laparoscopic 

cholecystectomies. N Engl J Med 324:1073-1078, 

1991. 

This classic paper is one of the fi rst to identify and report outcomes 

following laparoscopic cholecystectomy. 


Way LW, Stewart L, Gantert W, et al: Causes and prevention of 

laparoscopic bile duct injuries: Analysis of 252 cases from a 

human factors and cognitive psychology perspective. Ann Surg 

237:460-469, 2003. 

Intriguing article examining the human factor in the causation of bile 

duct injury. 

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36. Cosenza CA, Durazo F, Stain SC, et al: Current management 

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37. Owen CC, Bilhartz LE: Gallbladder polyps, cholesterolosis, 

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38. Ahrendt SA, Pitt HA, Kalloo AN, et al: Primary sclerosing 

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39. Rosen CB, Nagorney DM, Wiesner RH, et al: Cholangiocarcinoma 

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resection for hilar cholangiocarcinoma. Ann Surg 242:451- 

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41. Todani T, Watanabe Y, Toki A, et al: Carcinoma related to 

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42. Dixon E, Vollmer CM Jr, Sahajpal, A, et al: An aggressive 

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Ch. 54 – Biliary System

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