Biliary Tract Cancers
Gallbladder carcinoma is diagnosed approximately 5,000 times a year in the United States, making it the most common biliary tract tumor and the fifth most common gastrointestinal tract cancer. Approximately 4,500 cases of bile duct tumors occur each year in the United States.
Epidemiology
Gallbladder cancer
Gender. Women are more commonly afflicted with gallbladder cancer than are men, with a female to male ratio of 1.7:1.
Age. The median age at presentation of gallbladder cancer is 73 years.
Race. An incidence five to six times that of the general population is seen in southwestern Native Americans, Hispanics, and Alaskans.
Bile duct cancer
Gender. Bile duct tumors are found in an equal number of men and women.
Age. Extrahepatic bile duct tumors occur primarily in older individuals; the median age at diagnosis is 70 years.
Etiology and Risk Factors
Gallbladder cancer
The risk of developing gallbladder cancer is higher in patients with cholelithiasis and calcified gallbladders and in typhoid carriers. Gallstones are present in 70% or more of patients with gallbladder cancer and presumably cause chronic inflammation. The overall incidence of gallbladder cancer in individuals with cholelithiasis is 1% to 3% and in patients with so-called porcelain gallbladders, caused by chronic cholecystitis, 10% to more than 50%. In patients who have gallbladder polyps measuring more than 1 cm, the risk of cancer is high.
Bile Duct Cancer
Primary sclerosing cholangitis (PSC). Thirty percent of cholangiocarcinomas are diagnosed in patients with PSC with or without ulcerative colitis. The annual incidence of cholangiocarcinoma in patients with PSC is estimated at 1.5% per year; their lifetime risk of developing this malignancy is 10% to 15%. These patients have a highly abnormal biliary system, making diagnosis of cholangiocarcinoma difficult.
Ulcerative colitis. The incidence of bile duct cancer in patients with ulcerative colitis is 9 to 21 times higher than that in the general population. This risk does not decline after total colectomy for ulcerative colitis.
Other risk factors. Congenital anomalies of the pancreaticobiliary tree, parasitic infections, biliary papillomatosis, and Lynch syndrome are also associated with bile duct tumors. No association of bile duct cancer with calculi, infection, or chronic obstruction has been found.
Signs and Symptoms
Gallbladder cancer
Early and late disease. In the early stages, gallbladder cancer is usually asymptomatic. Later, symptoms similar to those of benign gallbladder disease arise; they include right upper quadrant pain, nausea, vomiting, fatty food intolerance, anorexia, jaundice, and weight loss. This nonspecificity of symptoms delays presentation for medical attention and contributes to the low curability of gallbladder cancer.
Physical findings. These may include tenderness, an abdominal mass, hepatomegaly, jaundice, fever, and ascites.
Bile duct cancer
Jaundice. This is the most frequent symptom found in patients with high bile duct tumors; it is present in up to 98% of such patients.
Nonspecific signs and symptoms. Patients who do not present with jaundice have vague complaints, including abdominal pain, weight loss, pruritus, fever, and an abdominal mass.
Diagnosis
Gallbladder cancer
Gallbladder carcinomas are often diagnosed at an advanced stage, such that by the time symptoms have developed, most tumors are unresectable.
Laboratory values. Findings in patients with gallbladder carcinoma are nonspecific but may include anemia, leukocytosis, and an elevated bilirubin level.
Ultrasonography. This diagnostic study is useful for defining a thickened gallbladder wall and may show tumor extension into the liver. It is valuable in measuring the size of a polyp.
CT and MRI. CT is more helpful than ultrasonography in assessing adenopathy and spread of disease into the liver, porta hepatis, or adjacent structures. MRI may be used to evaluate intrahepatic spread.
Cholangiography. Endoscopic retrograde cholangiopancreatography (ERCP), transhepatic cholangiography (THC), or magnetic resonance cholangiography may be useful in the presence of jaundice to determine the location of biliary obstruction and involvement of the liver.
Bile duct cancer
Cholangiocarcinoma may present earlier than gallbladder cancer by virtue of the development of biliary obstruction with jaundice, which may be painless. Tissue confirmation of suspected bile duct cancer can be difficult. The goals of the diagnostic evaluation include the determination of the level and extent of obstruction, the extent of local invasion of disease, and the identification of metastases.
Many patients with cholangiocarcinoma are thought to have metastatic adenocarcinoma of an unknown primary site, although occasionally the metastatic lesion may produce biliary dilatation without the primary lesion itself being radiographically visualized. Recently, microarray-based technology for genetic analysis has become available to help characterize tumors that are difficult to identify.
Ultrasonography. It is generally accepted that ultrasonography should be the first imaging procedure in the evaluation of the jaundiced patient.
CT. This diagnostic modality is a complementary test to ultrasonography, but both tests are accurate for staging in only 50% of patients and for determining resectability in fewer than 45% of patients.
Cholangiography. This diagnostic technique is essential to determine the location and nature of the obstruction. Percutaneous THC is used for proximal lesions, and ERCP is used for distal lesions. Magnetic resonance cholangiopancreatography may replace invasive studies in the near future. Histologic confirmation of tumor can be made in 45% to 85% of patients with the use of exfoliative or brush cytology during cholangiography.
Pathology
Gallbladder cancer
Histologic types. More than 85% of gallbladder neoplasms are adenocarcinomas, and the remaining 15% are squamous cell or mixed tumors.
TNM staging of gallbladder cancerRoute of spread. The initial route of spread of gallbladder cancer is locoregional rather than distant. For patients who undergo resection for presumed high-risk gallbladder masses or preoperatively defined disease limited to the gallbladder, 25% will have lymphatic involvement and 70% will have direct extension of disease into the liver defined at operation.
Bile duct cancer
Adenocarcinoma. Morphologically, more than 90% of bile duct tumors are adenocarcinomas. Three macroscopic appearances have been identified. The papillary and nodular types occur more frequently in the distal bile duct, whereas the sclerosing type is found in the proximal bile duct. Patients with papillary lesions have the best prognosis. Immunohistochemical staining may be positive for cytokeratin 7 and 20.
Other histologic types. Unusual malignant diseases of the biliary tract include adenosquamous carcinoma, leiomyosarcoma, and mucoepidermoid carcinoma.
Route of spread. Most bile duct tumors grow slowly, spreading frequently by local extension and rarely by the hematogenous route. Nodal metastases are found in up to one-third of patients.
Staging and Prognosis
Gallbladder cancer
Staging of perihilar bile duct tumors
Staging of distal bile duct tumorsGallbladder cancer is staged primarily at the time of surgery, and staging is determined by lymphatic involvement and extension of disease into adjacent structures (Table 5).
Stage. Survival of gallbladder carcinoma is directly related to disease stage. The 5-year survival rate is 83% for persons whose tumors are confined to the gallbladder mucosa; this rate decreases to 33% if the tumor extends through the gallbladder. For patients who have involvement of the lymph nodes or metastatic disease, 5-year survival rates range from 0% to 15%.
Type of therapy. Median survival is also improved in patients who have undergone curative resection, compared with those who have had palliative procedures or no surgery (17 months vs 6 and 3 months, respectively).
Bile duct cancer
More than 70% of patients with cholangiocarcinoma present with local extension, lymph node involvement, or distant spread of disease. The American Joint Committee on Cancer (AJCC) staging system for extrahepatic tumors is shown in Tables 6 and 7.
Stage. Survival for these patients is poor and is directly related to disease stage. Median survival time is 12 to 20 months for patients with disease limited to the bile ducts and 8 months or less when the disease has spread.
Tumor location. Survival is also related to tumor location, with patients who have distal lesions doing better than those with mid or proximal tumors.
Success of therapy. Curative resection and negative margins result in improved survival.
