Bile duct cancer, or cholangiocarcinoma, is a malignant tumor of the bile ducts within the liver (intrahepatic), or leading from the liver to the small intestine (extrahepatic). It is a rare tumor with poor outcome for most patients.
Description
Bile is a substance manufactured by the liver that aids in the digestion of food. Bile ducts are channels that carry the bile from the liver to the small intestine. Like the tributaries of a river, the small bile ducts in the liver converge into two large bile ducts called the left and right hepatic ducts. These exit the liver and join to form the common hepatic duct. The gallbladder, which concentrates and stores the bile, empties into the common hepatic duct to form the common bile duct. Finally, this large duct connects to the small intestine where the bile can help digest food. Collectively, this network of bile ducts is called the biliary tract.
Bile duct cancer originates from the cells that line the inner surface of the bile ducts. A tumor may arise anywhere along the biliary tract, either within or outside of the liver. Bile duct tumors are typically slow-growing tumors that spread by local invasion of neighboring structures and by way of lymphatic channels.
Demographics
Bile duct cancer is an uncommon malignancy. In the United States, approximately one case arises per 100, 000 people per year, but it is more common in Southeast Asia. It occurs in men only slightly more often than in women. The most common time of diagnosis is during the fifth and sixth decades of life.
Causes and symptoms
A number of risk factors are associated with the development of bile duct cancer:
Primary sclerosing cholangitis. This disease is characterized by extensive scarring of the biliary tract, sometimes associated with inflammatory bowel disease.
Choledochal cysts. These are abnormal dilatations of the biliary tract that usually form during fetal development. There is evidence that these cysts may rarely arise during adulthood.
Hepatolithiasis. This is the condition of stone formation within the liver (not including gallbladder stones).
Liver flukes. Parasitic infection with certain worms is thought to be at least partially responsible for the higher prevalence of bile duct cancer in Southeast Asia.
Thorotrast. This is a chemical that was previously injected intravenously during certain types of x rays. It is not in use anymore. Exposure to Thorotrast has been implicated in the development of cancer of the liver as well as the bile ducts.
Symptoms
Jaundice is the first symptom in 90% of patients. This occurs when the bile duct tumor causes an obstruction in the normal flow of bile from the liver to the small intestine. Bilirubin, a component of bile, builds up within the liver and is absorbed into the bloodstream in excess amounts. This can be detected in a blood test, but it can also manifest as yellowish discoloring of the skin and eyes. The bilirubin in the bloodstream also makes the urine appear dark. Additionally, the patient may experience generalized itching due to the deposition of bile components in the skin. Normally, a portion of the bile is excreted in stool; bile actually gives stool its brown color. But when the biliary tract is obstructed by tumor, the stools may appear pale.
Abdominal pain, fatigue, weight loss, and poor appetite are less common symptoms. Occasionally, if obstruction of the biliary tract causes the gallbladder to swell enormously yet without causing pain, the physician may be able to feel the gallbladder during a physical examination. Sometimes the biliary tract can become infected, but this is normally a rare consequence of invasive tests. Infection causes fever, chills, and pain in the right upper portion of the abdomen.
Diagnosis
Certain laboratory tests of the blood may aid in the diagnosis. The most important one is the test for elevated bilirubin levels in the bloodstream. Levels of alkaline phosphatase and CA 19-9 may also be elevated.
When symptoms, physical signs, and blood tests point toward an abnormality of the biliary tract, then the next step involves radiographic tests. Ultrasound and computed tomography (CT scan) are noninvasive and rapid. These tests can often detect the actual tumor as well as dilatation of the obstructed biliary tract. If these
tests indicate the presence of a tumor, then cholangiography is required. This procedure involves injecting dye into the biliary tract to obtain anatomic images of the bile ducts and the tumor. The specialist that performs this test can also insert small tubes, or stents, into a partially obstructed portion of the bile duct to prevent further obstruction by growth of the tumor. This is vitally important since it may be the only intervention that is possible in certain patients. Cholangiography is an invasive test that carries a small risk of infection of the biliary tract. The objective of these radiological tests is to determine the size and location of the tumor, as well as the extent of spread to nearby structures.
The treatment of bile duct tumors is usually not affected by the specific type of cancer cells that comprise the tumor. For this reason, some physicians forego biopsy of the tumor.
Treatment team
The treatment team may include the patient's primary physician, a surgeon, and a gastroenterologist who specializes in the stenting technique described above for palliation of bile duct strictures.
Clinical staging, treatments, and prognosis
Staging
Bile duct tumors are staged according to the tumor-node-metastasis (TNM) system of the American Joint Commission on Cancer. This staging scheme assesses the invasiveness of the tumor, the involvement of nearby lymph nodes, and the extent of distant metastasis.
Stage I tumors are confined to the bile duct itself.
Stage II tumors extend to the immediately adjacent tissues.
Stage III tumors have spread to associated lymph nodes.
Stage IV tumors have invaded local structures or have metastasized to distant structures.
A higher stage signifies worse prognosis.
Treatment
The only hope for cure lies with surgical resection (removal) of the tumor and all involved structures. Unfortunately, sometimes the cancer has already spread too far when the diagnosis is made. Thus, in the treatment of bile duct cancer, the first question to answer is if the tumor may be safely resected by surgery with reasonable benefit to the patient. If the cancer involves certain blood vessels or has spread widely throughout the liver, then resection may not be possible. Sometimes further invasive testing is required.
Angiography can determine if the blood vessels are involved. Laparoscopy is a surgical procedure that allows the surgeon to directly assess the tumor and nearby lymph nodes without making a large incision in the abdomen. Only about 45% of bile duct cancers are ultimately resectable.
If the tumor is resectable, and the patient is healthy enough to tolerate the operation, then the specific type of surgery performed depends on the location of the tumor. For tumors within the liver or high up in the biliary tract, resection of part of the liver may be required. Tumors in the middle portion of the biliary tract can be removed alone. Tumors of the lower end of the biliary tract may require extensive resection of part of the pancreas, small intestine, and stomach to ensure complete resection.
Unfortunately, sometimes the cancer appears resectable by all the radiological and invasive tests, but is found to be unresectable during surgery. In this scenario, a bypass operation can relieve the biliary tract obstruction, but does not remove the tumor itself. This does not produce a cure but it can offer a better quality of life for the patient.
Prognosis depends on the stage and resectability of the tumor. If the patient cannot undergo surgical resection, then survival is expected to be less than one year. If the tumor is resected, survival improves but is still dismal. Only 20% of these patients survive past five years.
Clinical trials
Studies of new treatments in patients are known as clinical trials. These trials seek to compare the standard method of care with a new method, or the trials may be trying to establish whether one treatment is more beneficial for certain patients than others. Sometimes, a new treatment that is not being offered on a wide scale may be available
to patients participating in clinical trials, but participating in the trials may involve some risk. To learn more about clinical trials, patients can call the National Cancer Institute (NCI) at 1-800-4-CANCER or visit the NCI web site for patients at <http://www.cancertrials.nci.nih.gov>.
Prevention
Other than the avoidance of infections caused by liver flukes, there are no known preventions for this cancer.
Resources
BOOKS
Ahrendt, Steven A. and Henry A. Pitt. "Biliary Tract." In Sabiston Textbook of Surgery, edited by Courtney Townsend Jr., 16th ed. Philadelphia: W.B. Saunders Company, 2001, pp. 1076-1111.
Callery, Mark P. and William C. Meyers. "Bile Duct Cancer."In Current Surgical Therapy, edited by John L. Cameron, sixth ed. St Louis: Mosby, 1998, pp.455-161.
"Cholangiocarcinoma." In Clinical Oncology, edited by Abeloff, Martin D., second ed. New York: Churchill Livingstone, 2000, pp.1722-1723.
