eMedicine Specialties > General Surgery > Abdomen

Bile Duct Tumors

Author: Todd A Nickloes, DO, Assistant Professor of Surgery, Division of Trauma/Critical Care, University of Tennessee Medical Center
Coauthor(s): Brian Reed, MD, Staff Physician, Department of Surgery, University of Tennessee Medical Center; LaMar O Mack, MD, Staff Physician, Department of Surgery, University of Tennessee Medical Center; Ravi Pokala Kiran, MBBS, MS, FRCS (Eng), FRCS (Glas), Staff Physician, Department of General Surgery, St Mary's Hospital; Naveen Pokala, MBBS, MS, FRCS, Staff Physician, Department of Surgery, Bronx Lebanon Hospital
Contributor Information and Disclosures

Updated: Mar 13, 2009

Introduction

Tumors of the biliary tract (see image below and Image 1) are uncommon but serious problems. The spectrum of lesions ranges from benign tumors, such as adenomas, to malignant lesions, such as adenocarcinomas. This discussion excludes tumors of the gallbladder, which are discussed separately.

Cholangiography via a transhepatic or endoscopic approach is required to define the biliary anatomy and extent of the lesion. Magnetic resonance cholangiography is a noninvasive alternative available in an increasing number of centers.

The anticipated course of most cases of bile duct tumors includes recurrent biliary obstruction with infectious complications, local spread, and death in 6-12 months. Treatment depends on the site and extent of the lesion, and surgical resection improves survival and prognosis.

Related eMedicine topics:
Biliary Disease
Biliary Cystadenoma/Cystadenocarcinoma
Biliary Obstruction
Gallbladder, Carcinoma
Gallbladder Tumors
Hepatic Adenoma

History of the Procedure

Bile duct tumors have been recognized for over a century. Musser first reported 18 cases of primary extrahepatic biliary cancer. Sako and colleagues found 570 cases of extrahepatic bile duct cancer when reviewing literature from 1935-1954. Malignancy of the intrahepatic bile ducts was described later, by Altmeir (1957); Klatskin described cancer of the hepatic duct bifurcation in 1965.

Problem

Tumors of the bile duct are rare. They constitute about 2% of all cancers found at autopsy. Benign adenomas or papillomas are exceedingly rare compared with malignant tumors. Even benign tumors tend to recur after excision and have been reported to undergo malignant change. Patients usually present with jaundice. Occult gastrointestinal hemorrhage may occur.

Cholangiocarcinomas, the most important primary tumors of the bile ducts, may involve either the intrahepatic or the extrahepatic biliary ducts. The former variety is the second most common primary hepatic malignancy after hepatocellular carcinoma. Patients with intrahepatic cholangiocarcinoma (cholangiocellular carcinoma) have a poor prognosis, and the tumor metastasizes early. This tumor has been associated with thorium dioxide (Thorotrast, an intravenous contrast medium used many years ago), ulcerative colitis, and sclerosing cholangitis; surgery is the only chance of treatment.

Bile duct cancer differs from gallbladder cancer in that it is distributed more evenly between males and females, and the course is more prolonged. All cholangiocarcinomas are slow growing and locally infiltrative, and they metastasize late.

Related eMedicine topics:
Cholangiocarcinoma [Oncology]
Cholangiocarcinoma [Radiology]

Frequency

The annual incidence of bile duct cancer in the United States is approximately 1 case per 100,000 people. In autopsy studies, the incidence varies from 0.01-0.46%.

Bile duct cancer is more common in Israel and Japan, and in American Indians, than it is in the general US population. The prevalence of carcinoma of the gallbladder and bile ducts in England and Wales is 2.8 cases per 100,000 females and 2 cases per 100,000 males.

Etiology

The risk factors for bile duct cancer include the following^2,3 :

• Family history of congenital fibrosis or cysts
  • Congenital hepatic fibrosis
  • Cystic dilatation (ie, Caroli disease)
  • Choledochal cyst
  • Polycystic liver
  • Von Meyenburg complexes
• Parasitic infestations
  • In the Far East (ie, China, Hong Kong, Korea, Japan), where Clonorchis sinensis (a liver fluke) is prevalent, intrahepatic cholangiocarcinoma accounts for 20% of primary liver tumors.
  • Opisthorchis viverrini is found in Thailand, Laos, and West Malaysia.
• Gallstones and hepatolithiasis - The risk of extrahepatic bile duct cancer is significantly decreased 10 years or more after cholecystectomy, thus suggesting a link between bile duct cancer and gallstones. The risk is much less than that of carcinoma of the gallbladder, which is itself quite rare.
• Primary sclerosing cholangitis (PSC) - Among patients undergoing liver transplantation for PSC, 10-30% are found to have unsuspected cholangiocarcinoma in the hepatectomy specimen. Carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 have, in combination, a sensitivity of 66% and a specificity of 100% in diagnosing cholangiocarcinoma in patients with PSC.
• Ulcerative colitis either with or without coexisting PSC - The majority of patients with PSC who develop cholangiocarcinoma have ulcerative colitis. The incidence of cholangiocarcinoma in patients with ulcerative colitis and PSC is further increased if they have associated colorectal malignancy. Patients with PSC who develop a rapid deterioration in clinical status with worsening jaundice, weight loss, and abdominal discomfort and who have evidence of intrahepatic biliary dilatation on ultrasonograms¹ of the abdomen are suspected of having cholangiocarcinoma.
• Toxic materials
  • Thorium dioxide (Thorotrast)
  • Radionuclides
  • Carcinogens (eg, arsenic, dioxin, nitrosamines, polychlorinated biphenyls)
• Drugs
  • Oral contraceptives
  • Methyldopa
  • Isoniazid
• Chronic typhoid carriers appear to have a greater incidence of hepatobiliary cancer, including cholangiocarcinoma.
• Bile duct cancers are also associated with biliary cirrhosis.

Pathophysiology

Bile duct tumors cause bile duct obstruction with biliary stasis and a consequent alteration of liver function tests. Prolonged biliary obstruction causes hepatocellular dysfunction, progressive malnutrition, coagulopathy, pruritus, renal dysfunction, and cholangitis.

Pathogenesis of bile duct cancer

Long-standing inflammation with the development of chronic injury is the final common pathway for tumorigenesis in the bile ducts in patients with preexisting inflammatory conditions.

Parasitic organisms induce deoxyribonucleic acid (DNA) changes and mutations through the production of carcinogens and free radicals and the stimulation of cellular proliferation of the biliary epithelium, which is thought to cause cancer.

Bacterially induced, endogenous, carcinogen-derived bile salts, such as lithocholate, also have been implicated in the pathogenesis. These implications are supported by the findings of some epidemiologic studies and in the higher incidence in typhoid carriers. Point mutations in codon 12 of the K-ras oncogene are found in cholangiocarcinoma.⁴ Aneuploidy is found in hilar cholangiocarcinoma and is associated with neural invasion and shorter survival. P53 protein is particularly expressed in high-grade mid-duct and distal duct cholangiocarcinomas.⁵ Cholangiocarcinoma cells contain somatostatin-receptor ribonucleic acid (RNA), and cell lines have specific receptors. Cell growth is inhibited by somatostatin analogues. Cholangiocarcinomas have been detected using radionuclide scanning with a labeled somatostatin analog.

Presentation

Patients with bile duct tumors are typically elderly; the average age is 60-65 years. In contrast to carcinoma of the gallbladder, only a minor sex difference in incidence exists, with a very slight male preponderance.

Symptoms

• Jaundice is the usual presenting symptom, followed by pruritus, which is a distinguishing feature from biliary cirrhosis. Jaundice is delayed if only 1 main hepatic duct is involved, because the unaffected lobe of the liver can compensate.
• One third of patients present with mild epigastric pain.
• Diarrhea, anorexia, and weight loss are the other presenting symptoms.

Examination findings

• Patients usually are deeply jaundiced.
• Cholangitis usually occurs only if previous endoscopic, percutaneous, or surgical biliary interventions have been performed.
• The liver may be large and smooth.
• In distal bile duct tumors, a distended, nontender gallbladder may be present. If such patients undergo surgery and exploration confirms absence of involvement of the junction of the cystic duct and common bile duct by tumor, the gallbladder may be used for bypass procedures.
• Cases with involvement of only 1 duct at the hilum present with mild abdominal pain, unilobar hepatic enlargement, and elevated serum alkaline phosphatase and gamma glutamyl transferase without any elevation of serum bilirubin.

Indications

Indications for bile duct tumor surgery include the following:

• The tumor is resectable. The criteria for resectability include absence of liver metastases, absence of carcinomatosis, and absence of vascular invasion.
• The patient is fit for surgery.

If the tumor is limited to the bifurcation of the hepatic ducts or a single lobe of the liver or if it involves the portal vein or hepatic artery on the same side, the lesion may be resectable. Preoperative imaging is aimed at establishing whether a viable unit of liver that is large enough to maintain adequate liver function will remain after surgical removal of the tumor. The remaining liver tissue must contain a normal branch of the portal vein and hepatic artery and must also contain a bile duct large enough to anastomose to the bowel (see image below and Image 1).

Relevant Anatomy

The liver is an epithelial-mesenchymal outgrowth of the caudal part of the foregut, with which it retains its continuity by the biliary tree. Hepatocytes in the liver are arranged in anatomic plates called hepatic laminae, which are lined by endothelium and separated from each other by hepatic sinusoids. Bile secreted by hepatocytes is collected in a network of canaliculi, which drain into hepatic ductules. In turn, the hepatic ductules join other ductules, forming the biliary tree.

The main right and left hepatic ducts from the liver unite near the right end of the porta hepatis as the common hepatic duct, which descends for about 1 inch before being joined by the cystic duct to form the common bile duct (CBD). The common hepatic duct lies to the right of the hepatic artery and anterior to the portal vein.

The CBD is 3 inches long and consists of 3 parts. The upper third lies in the free border of the lesser omentum anterior to the portal vein and to the right of the hepatic artery. The middle third lies behind the first part of the duodenum and slopes down to the right, eventually lying on the inferior vena cava. The lower third slopes down to the right behind the head of the pancreas, lying in a deep groove on the posterior surface of this organ. It opens, in common with the pancreatic duct, into the ampulla of Vater, which is situated in the second part of the duodenum.

The hepatic ducts and the upper and middle portions of the CBD are supplied with blood primarily by rami from the cystic artery. In addition, the middle portion of the CBD is supplied by rami from the right hepatic and posterior superior pancreaticoduodenal arteries. The latter also supplies blood to the lower portion of the CBD. Veins from the upper portion of the biliary tree enter the liver, while those from the lower portion drain into the portal vein.

With regard to lymphatic drainage, the upper portion of the biliary tree drains into the hepatic nodes, while the lower portion drains into the inferior hepatic and upper pancreaticosplenic nodes. Metastases from bile duct tumors can occur in lymph nodes lying along the common hepatic artery and the celiac axis and from distal lesions in the retropancreatic and superior mesenteric nodes.

Anatomically, the upper third of the biliary tree extends from the confluence of the hepatic ducts to the level of the cystic duct, the middle third extends from the cystic duct to the upper part of the duodenum, and the lower third extends from that level to the papilla of Vater.

The reported distribution of bile duct tumors is 55% in the upper third, 15% in the middle third, and 10% in the lower third. Of these tumors, 10% are diffuse.

Tumors of the bifurcation of the hepatic ducts are classified by the Bismuth classification, as follows:

• Type I - Involvement of the common hepatic duct
• Type II - Involvement of the bifurcation without involvement of the secondary intrahepatic ducts
• Type III a - Extends into the right secondary intrahepatic duct
• Type III b - Extends into the left secondary intrahepatic duct
• Type IV - Involvement of the secondary intrahepatic ducts on both sides

Contraindications

• Unresectable tumors - If tumors are extensive or fixed to adjoining structures, including the main portal vein or hepatic artery, they are unresectable. Cholangiogram findings of invasion of the secondary hepatic duct in both lobes of the liver or angiographic evidence of encasement of the main portal vein or hepatic artery indicate unresectability.
• Metastases including diffuse peritoneal involvement
• Vascular invasion
• Patients who are at high risk from general anesthesia and surgery because of general medical conditions
• Advanced age

• Search for CME/CE on This Topic »

• Cholangiocarcinoma (Radiology)