Bile duct cancer

ALSO KNOWN AS: Intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, perihilar cancer, Klatskin tumors

RELATED CONDITIONS: Sclerosing cholangitis, liver cancer

DEFINITION: Bile is a fluid produced by the liver that aids in the digestion of fats. Bile is transported from the liver through a series of tubes, called bile ducts, to either the gallbladder, which stores and concentrates the bile, or directly to the small intestine. Bile duct cancer forms in the inner layer of these ducts. It can develop in the smaller ducts within the liver, where it is called intrahepatic cholangiocarcinoma, or in ducts outside the liver, where it is called extrahepatic cholangiocarcinoma. Extrahepatic cholangiocarcinoma is divided into two types, depending on where the cancer originates. Perihilar cancer develops in the bile duct close to its exit point from the liver. Distal bile duct cancer develops close to where the bile duct empties into the small intestine. Approximately 95 percent of cholangiocarcinomas are adenocarcinomas.

Risk factors: Conditions that irritate the bile ducts have been linked to an increased risk of developing cholangiocarcinoma. These disorders include bile duct stones, congenital bile duct cysts, viral hepatitis, sclerosing cholangitis (especially in people who smoke), and nonviral cirrhosis. Other risk factors include ulcerative colitis, liver flukes (parasites found in Asian countries), and obesity. Exposure to some chemicals, including polychlorinated biphenyls, dioxin, and Thorotrast (previously used in X-ray diagnosis), also increase the risk of developing this cancer.

Etiology and the disease process: The exact cause of most cholangiocarcinomas is unknown. Patients with no known risk factors often develop this cancer. Cholangiocarcinoma is a slow-growing cancer that can remain undetected until it has reached an advanced stage. It originates in the mucosal cells that line the ducts and spreads throughout the layers of the ducts. Eventually, the ducts become blocked, preventing the flow of bile. When the cancer grows through the walls of the ducts, it can invade the liver, gallbladder, small and large intestines, and blood vessels that serve the liver.

Incidence: Primary cholangiocarcinoma is a rare disease that is most common in Asian countries because of its association with liver flukes. Approximately 90 percent of cholangiocarcinomas are extrahepatic, with about 65 percent perihilar tumors and 25 percent distal cancers. Around eight thousand people in the United States develop this cancer each year, most of whom are men, and about 70 percent of them are older than age sixty-five. An increase in the incidence of intrahepatic cholangiocarcinoma of 149 percent from 2001 to 2017, from 0.48 to 1.38 per 100,000 people per year, could possibly be linked to improved diagnostic testing or reclassification. However, an 81 percent increase in young patients was also notable. Environmental and geographical factors, such as parasitic infections and liver fluke increases, may be linked to the changes.

Symptoms: Most cholangiocarcinomas do not produce symptoms until they are in the advanced stages. Jaundiced and itchy skin, dark urine, and pale bowel movements may occur if the ducts become blocked and bilirubin, a chemical in bile, is forced into the blood vessels. Other symptoms include fever, bloating, loss of appetite, weight loss, and fatigue.

Screening and diagnosis: There are no screening tests for cholangiocarcinoma. Diagnosis typically is made during surgery for a gallbladder disorder or during diagnostic tests for other conditions. Blood chemistry and liver function tests, though not specific for this cancer, may show abnormal results. Tumor-marker studies may show the presence of carcinoembryonic antigen and cancer antigen 19-9 (CA 19-9). Ultrasound, computed scanning, magnetic resonance imaging, endoscopic retrograde cholangiopancreatography, positron emission tomography, and percutaneous transhepatic cholangiography are imaging studies used to diagnose cholangiocarcinoma, determine treatment options, and assess the spread of the disease. and brushing may be performed to obtain cells for differential testing. Staging is based on the number of tumors present and the extent of their spread to other organs.

Treatment and therapy: Traditional treatment for cholangiocarcinoma includes surgery, chemotherapy, and radiation therapy. Surgery for intrahepatic cholangiocarcinoma always involves the removal of part of the liver and is a difficult procedure. In many cases, the cancer is too far advanced at the time of diagnosis for surgery to be successful or safe for the patient. Surgery for extrahepatic cholangiocarcinoma usually involves the removal of the bile duct, gallbladder, and parts of the liver and small intestine. It may also include the of part or all of the pancreas. When the cancer cannot be removed, symptoms may be relieved by creating a bypass around the tumor blocking the bile duct or inserting a biliary drain.

Chemotherapy and radiation therapy may be used before surgery to shrink a tumor, in place of surgery when the tumor is inoperable, and after surgery to destroy cells that may have spread. Common chemotherapeutic agents used include fluorouracil, cisplatin, doxorubicin, and gemcitabine. Radiation is commonly administered in the form of tiny seeds that are implanted into the duct, delivering high-dose radiation directly to the tumor.

Other forms of treatment that are being tested include using a person’s own immune system to fight the cancer, introducing viruses that seek out and destroy cancer cells, and photodynamic therapy, in which a special light is used to activate a drug that has been administered for the purpose of destroying cancer cells.

Prognosis, prevention, and outcomes: The overall survival rate for cholangiocarcinoma is generally poor. Localized cholangiocarcinoma that has not spread outside the bile ducts has a five-year survival rate of 18 to 24 percent. Regional cancer that has spread to nearby lymph nodes or structures has a five-year survival rate of around 10 percent, and distant cholangiocarcinoma, which has spread to distant organs or parts of the body such as the lungs, has a five-year survival rate of 2 to 5 percent. Although there is no definitive way to prevent this disease, reducing exposure to its risk factors may prevent its development.

Bibliography

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