Cholangiocarcinoma (CCA), or bile duct cancer, is a type of rare cancer that grows in the small tubes that carry bile, a fluid that helps with digestion. These tubes are called the bile ducts. The bile ducts connect the liver to the gall bladder and small intestine.

There are three types of cholangiocarcinoma that are named for where they grow in the bile ducts:

• Intrahepatic cholangiocarcinoma grows in the parts of the bile ducts that are in the liver. This is the least common form of cholangiocarcinoma and accounts for only 10% of all cases.
• Hilar cholangiocarcinoma grows in the bile ducts right outside of the liver. It is also called perihilar cholangiocarcinoma.
• Distal cholangiocarcinoma grows in the parts of the bile ducts near the small intestine.

Sometimes, hilar cholangiocarcinoma and distal cholangiocarcinoma are grouped together and called extrahepatic cholangiocarcinoma.

Cholangiocarcinoma is rare. On average, it affects fewer than 6 in 100,000 people around the world. In the United States, cholangiocarcinoma affects about 8,000 people per year. In some places, though, cholangiocarcinoma is more common. For example, in northeast Thailand, cholangiocarcinoma occurs in about 110 per 100,000 people. Most people diagnosed with cholangiocarcinoma are above the age of 65. Cholangiocarcinoma is slightly more common in men than women.

Cancers occur when a buildup of mutations in critical genes—those that control cell division, for example—allow cells to grow and divide uncontrollably to form a tumor. In most cases of cholangiocarcinoma, these genetic changes are acquired during a person's lifetime and are present only in the bile duct cells that give rise to the tumor. The genetic changes, which are called somatic mutations, are not inherited. Somatic mutations in many different genes have been found in cholangiocarcinoma. Some of these genes act as tumor suppressors, which means they help keep the growth and division of cells tightly regulated. Mutations in or deletions of tumor suppressor genes can allow cells to grow and divide without control or order, which is a hallmark of cancer. Other genes associated with cholangiocarcinoma are oncogenes; when they are turned on (activated) abnormally, these genes have the potential to cause normal cells to become cancerous. Identifying somatic mutations in cholangiocarcinoma may provide clues to how quickly the cancer will grow and spread, and which treatments might be most effective.

Researchers have also investigated inherited variations in several genes as possible risk factors for cholangiocarcinoma. These genetic changes, which are classified as germline mutations, are present in essentially all of the body's cells. However, no specific inherited changes have been found to be major risk factors for this disease.

Several non-genetic risk factors for cholangiocarcinoma have been identified. These include a bile duct disease called primary sclerosing cholangitis, bile duct stones or cysts, and exposure to certain chemical toxins used in manufacturing. In Southeast Asia, infection with parasitic worms that live in the human bile ducts greatly increase the risk of developing cholangiocarcinoma. Other risk factors that have been studied include long-term infection with viral hepatitis B or C, scarring of the liver (cirrhosis), and chronic diseases such as inflammatory bowel disease and diabetes. Researchers suspect that certain lifestyle factors, including smoking, alcohol use, and obesity, may also contribute to the risk of developing cholangiocarcinoma.

Studies suggest that a combination of genetic, environmental, and lifestyle factors influence whether a person will develop cholangiocarcinoma. However, most people who develop the disease do not have any of the identified risk factors.

Cholangiocarcinoma is not inherited. Studies suggest that blood relatives of a person with cholangiocarcinoma may have an increased risk of developing this cancer compared with the general population. However, most people with cholangiocarcinoma do not have a family history of the disease.

Most people with cholangiocarcinoma do not have symptoms when it first starts. Later, when the tumor gets larger, symptoms can include:

• Yellow skin and eyes (jaundice)
• Itching
• Unintentional weight loss
• Abdominal pain

Lab Tests: If you have symptoms of cholangiocarcinoma, your doctor will order lab tests of your blood to check your bilirubin levels. Bilirubin is a substance in your blood that may be a sign that something is wrong with your liver, bile ducts, or gallbladder. Your doctor may also look for liver enzymes in your blood, called a liver function test.

Imaging: Your doctor will use imaging scans such as ultrasound, CT, MRI, and X-rays to look at where the tumor is and how big it is. They will also check for signs that the tumor has spread to other parts of the body. Your doctor may also use endoscopy to look inside the body.

Biopsy: To check if the tumor is cholangiocarcinoma your doctor will do a biopsy, taking a small sample from the tumor with a needle. An expert, called a pathologist, will study cells from the sample under the microscope to see what kind of tumor it is. A sample of your tumor may also be taken during endoscopy.

Treatment for each patient will be unique. You should go to an expert in cholangiocarcinoma treatment to decide the best approach for you. You can contact MyPART for help finding experts near you.

Treatment options to discuss with your doctor include:

Surgery: In some cases, cholangiocarcinoma can be removed with surgery. This is the best chance for cholangiocarcinoma to be cured. Surgery to remove cholangiocarcinoma is complex, so you will want to go to a surgeon with experience in bile duct surgery.

Radiation therapy: Radiation therapy can be used before or after surgery. Or it can be the main treatment if surgery is not an option. External radiation therapy uses a beam of energy aimed at the tumor. Internal radiation therapy uses small pieces of radioactive material placed inside the tumor to kill the tumor cells.

Chemotherapy: Chemotherapy can be used with radiation therapy. Chemotherapy is often used when cholangiocarcinoma has spread to other parts of the body.

Targeted therapy: Targeted therapy is aimed at the changes in cancer cells that help them grow, divide, and spread. In some cholangiocarcinomas, the cancer cells have changes in the FGFR2 gene, which helps the cancer cells grow out of control. In these cases, a FGFR2 inhibitor (pemigatinib) can help treat cholangiocarcinoma.

Immunotherapy: Immunotherapy helps the body’s immune system fight cancer cells. Doctors are studying if immunotherapy can help treat cholangiocarcinoma in clinical trials.

The estimate of how a disease will affect you long-term is called prognosis. Every person is different and prognosis will depend on many factors, such as:

• Where the tumor is in your body
• If the cancer has spread to other parts of your body
• How much of the tumor was taken out during surgery

Doctors estimate cholangiocarcinoma survival rates by how groups of people with this cancer have done in the past. Because there are so few people with cholangiocarcinoma, these rates may not be very accurate. The survival rates also don’t take into account newer treatments.

For people with extrahepatic cholangiocarcinoma, 10% are alive 5 years after diagnosis. For people with intrahepatic cholangiocarcinoma that has been found at an early stage, 24% are alive 5 years after diagnosis. But if not found early, 8% are alive 5 years after diagnosis

If you want information on your prognosis, it is important to talk to your doctor.