Bile Duct Cancer (Cholangiocarcinoma)

What is Bile Duct Cancer?

The bile duct is a thin tube, about 4 to 5 inches long, that reaches from the liver to the small intestine. The major function of the bile duct is to move a fluid called bile from the liver and then gallbladder to the small intestine, where it helps digest the fats in foods.

The bile duct system has different parts. The part within the liver is described as intrahepatic. Small branches within the liver are called intrahepatic bile ducts, and ultimately converge to form two branches. They exit the liver and join to form one duct in an area called the hilum. A third branch extending from the gall bladder, joins the merged duct, developing into one common bile duct. The common bile duct passes through part of the pancreas before emptying into the small intestine.

Bile duct cancers have different names, depending on where they develop.

These cancers develop in the smaller bile duct branches inside the liver.

These develop in the branches of the bile ducts outside of the liver. There are two main types:

Perihilar Bile Duct Cancers develop at the hilum, where the two smaller branches leave the liver and merge into one duct. They are also called Klatskin tumors. These are the most common type of bile duct cancer.

Distal or Distal Extrahepatic Bile Duct Cancers are found further down the duct, closer to the small intestine.

More than 95% of bile duct cancers are adenocarcinomas, which means they start in glandular cells. Bile duct adenocarcinomas develop from the mucus glands that line the inside of the duct.

Risk Factors

Research is improving our understanding of bile duct cancer and its causes. The following are known risk factors for the disease:

Liver Diseases: Having colitis or certain liver diseases can increase the risk of developing extrahepatic bile duct cancer. These include:

  • Primary sclerosing cholangitis
  • Chronic ulcerative colitis
  • Choledochal cysts
  • Cirrhosis – This is often caused by alcohol use or hepatitis
  • Hepatitis B or C
  • Infection with a Chinese liver fluke parasite
  • Increasing age
  • Obesity
  • Diabetes: Having type 1 or type 2 diabetes increases your risk
  • Exposure to chemicals such as dioxins or nitrosamines

Signs and Symptoms

These symptoms may be caused by bile duct cancer or by other conditions. Consult a doctor if any of the following occur:

  • Jaundice (yellowing of the skin or whites of the eyes)
  • Pain in the abdomen
  • Fever
  • Itchy skin
  • Loss of appetite/weight loss

Diagnosis

The diagnosis of bile duct cancer requires a physical exam as well as blood tests and imaging of your liver and bile ducts. Once you learn the results of the tests or procedures, you will be able to work with your health care team to make thoughtful decisions.

Tools for Diagnosis

Some of the tests that you may undergo as doctors determine if you have bile duct cancer include:

Physical Exam

A doctor will collect information on your health history and habits, take your temperature and blood pressure and check for signs of disease, such as lumps or anything else unusual.

Liver Function Tests 

A procedure in which a blood sample is checked to measure the amounts of certain substances released into the blood by the liver. A higher than normal amount of a substance can be a sign of liver disease that may be caused by extrahepatic bile duct cancer.

Ultrasound Exam 

A procedure in which high-energy sound waves (ultrasound) are bounced off internal tissues or organs and make echoes. The echoes form a picture of body tissues called a sonogram.

CT Scan

Detailed pictures of areas inside the body are taken from different angles. A dye may be swallowed or injected into a vein to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography or computerized axial tomography.

MRI

A procedure that uses a magnet, radio waves and a computer to make a series of detailed pictures of areas inside the body. This procedure is called magnetic resonance imaging (MRI).

ERCP

A procedure to x-ray the ducts that carry bile to and from the gallbladder. An endoscope is passed through the mouth, esophagus and stomach into the small intestine. A smaller tube is then inserted through the endoscope. A dye is injected through the smaller tube into the ducts and the x-ray is taken.

PTC

A procedure to x-ray the liver and bile ducts. A thin needle is inserted through the skin below the ribs and into the liver. Dye is injected into the liver or bile ducts and an x-ray is taken. If a blockage is found, a thin, flexible tube called a stent is sometimes left in the liver to drain bile into either the small intestine or a collection bag outside the body.

Biopsy

A sample of cells or tissues is removed and viewed under a microscope to check for signs of cancer. The sample may be taken using a thin needle inserted into the duct during an x-ray or ultrasound. This is called a fine-needle aspiration biopsy (FNA.) The biopsy is usually done during PTC or ERCP, where a brushing of the bile duct can be taken.

Staging

If cancer is diagnosed, the doctor needs to know the stage, or extent, of the disease to determine the best treatment. Staging is used to find out whether the cancer has spread, and if so, to which parts of the body. This is done by obtaining imaging studies of areas of your body where the cancer may have spread, including your lungs, abdomen, and possibly bones. If your cancer spreads to the bone, visit our bone metastases page.

The following stages are used for extrahepatic bile duct cancer:

In stage 0, abnormal cells are found in the innermost layer of tissue lining the extrahepatic bile duct. These abnormal cells may become cancer and spread into nearby normal tissue. Stage 0 is also called carcinoma in situ.

In stage I, cancer has formed. Stage I is divided into stage IA and stage IB.

  • Stage IA - The cancer is found in the bile duct only.
  • Stage IB - The cancer has spread through the wall of the bile duct.

 

Stage II is divided into stage IIA and stage IIB.

  • Stage IIA - Cancer has spread to the liver, gallbladder, pancreas or to either the right or left branch of either the hepatic artery or to the right or left branch of the portal vein.
  • Stage IIB - Cancer has spread to nearby lymph nodes, through the wall of the bile duct or has spread to the liver, gallbladder, pancreas or to the right or left branch of either the hepatic artery or the portal vein.

 

In stage III, cancer has spread to the main portal vein, both its branches, or to the hepatic artery or other nearby organs or tissues, such as the colon, stomach, small intestine or abdominal wall. Cancer may have spread to nearby lymph nodes.

In stage IV, cancer has spread to lymph nodes and other distant organs.

Biomarkers for Diagnosis and Staging

Biomarkers are features of your tumor that can be measured to help guide treatment. In recent years, doctors have learned more about the biology of cancer. They have found specific changes in a gene or cell that help cancer grow and spread. They have developed new drugs to treat cancers with these changes. Doctors can test for biomarkers—or signs—that these drugs might work against the cancer. Biomarkers are sometimes called molecular markers, genomic markers, or cancer markers. New biomarkers and drugs to treat them are being developed all the time.

Your doctor will test your blood for the presence of CEA and CA 19-9. These are proteins secreted by cancer cells. The tests can often predict if cancer is growing and spreading. Testing is done at diagnosis and again later in treatment. Doctors sometimes use this measure to see how well treatment is working.

For advanced cancer, you should also ask to have your tumor tested for the specific genomic alterations like MSI, FGFR2 alteration, and IDH1 mutation. Tumors that test positive can be treated with a targeted therapy.

Treatments & Side Effects

Your treatment options depend on the stage of cancer, your overall health, and your preferences about treatment. In metastatic disease, the location and extent of the cancer is also important. In all cases, treatment should be individualized for you. Although cancers are classified into particular stages, each person is unique.

The following are standard treatments for bile duct cancer:

Surgery

Common surgical procedures used to treat bile duct cancer include:

  • Removal of the Bile Duct: If the tumor is small and only in the bile duct, the entire bile duct may be removed. A new duct is created by connecting the duct openings in the liver and to the intestine. Lymph nodes are removed and viewed under a microscope to see if they contain cancer. 
  • Partial Hepatectomy: Removal of the part of the liver where cancer is found. The part may be a piece of tissue, an entire lobe or a larger part of the liver, along with some normal tissue around it. 
  • Whipple Procedure: A surgical procedure in which the head of the pancreas, the gallbladder, part of the stomach, part of the small intestine and the bile duct are removed. Enough of the pancreas is left to make digestive juices and insulin. 
  • Surgical Biliary Bypass: This is done if the tumor cannot be removed but is blocking the small intestine and causing bile to build up in the gallbladder. During this procedure, the gallbladder or bile duct will be cut and sewn to the small intestine to create a new pathway around the blocked area. 
  • Stent Placement: If the tumor is blocking the bile duct, a stent (a thin tube) may be placed in the duct to drain bile that has built up in the area. The stent may drain to the outside of the body or to the small intestine. 
  • Liver Transplant: The entire liver and bile ducts are removed. The liver is replaced by a healthy liver from a donor. This surgery is only possible if a donor match is found. There are strict criteria for a donor match.

Common side effects of surgery depend on the type of surgery done. They may include pain (often temporary), fatigue, the risk of infection at the surgical site, scarring, and numbness (often temporary).

If you have a transplant, your doctor will watch closely for signs of either infection or rejection of the new liver. You may be given antibiotics and immunosuppressants. Ask about the side effects of any drugs you are taking. Do not take acetaminophen (Tylenol*) unless told by your doctor to do so. It can damage the liver.

Radiation Therapy

Radiation therapy is the use of high-energy rays to kill or damage cancer cells. The goal is to damage as many cancer cells as possible without harming healthy tissue. To lessen damage, doses are very precise, and treatment is often spaced out. There are two types of radiation therapy that can be used for bile duct cancer:

  • External radiation therapy uses a machine outside the body to direct rays at the cancer.
  • Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires or catheters that are placed directly into or near the cancer.

Most side effects of radiation therapy are temporary, but some rare serious side effects can be permanent. For external radiation therapy, some additional side effects may occur, such as painful sores in the mouth and throat, dry mouth or thick saliva, and painful swallowing, which typically improves within a few weeks of finishing treatment.

Chemotherapy

Chemotherapy involves the use of drugs to destroy cancer cells. It is a systemic (whole body) treatment. 

Learn about chemotherapy.

Targeted Therapy

Targeted therapy aims to more precisely attack cancer cells. These drugs target changes in the genes or proteins of cancer cells that help them grow, divide, and spread.

Targeted therapies are being tested to manage bile duct cancers. Some are even approved by the FDA. There are targeted therapies available for the FGFR2 alteration, the IDH1 mutation, and for MSI high cancers. Ask your doctor if you can get tested to see if these therapies would work for you.

Learn about targeted therapy.

Palliative Care

If you have symptoms or side effects, you may receive palliative care or want to ask for it. This care is not designed to treat the cancer itself. Instead, it will address possible symptoms caused by cancer or side effects from treatments such as pain.

Learn about palliative care.

Clinical Trials

Be sure to ask about clinical trials. These are research studies to test new treatments or learn how to use current treatments better. In some cases, the treatments with the best chance of success may be available only through clinical trials. If you have cancer that has come back or spread, it is especially important to ask about clinical trials.

Learn about clinical trials.