Bile duct structure and function
The biliary system produces a fluid called bile, which helps digest food. Bile is made in the liver and stored in the gallbladder. The bile ducts are tree-like structures within and around the liver and gallbladder. They carry bile from the liver to the upper part of the small intestine (duodenum).
Biliary cancer types
Intrahepatic bile duct cancer: Intrahepatic bile duct cancer, or intrahepatic cholangiocarcinoma, occurs in the bile ducts within the liver. It accounts for about 10% of bile duct cancer cases. It is often misdiagnosed as liver cancer. Although rare, the number of intrahepatic bile duct cancer cases is increasing.
Extrahepatic bile duct cancers: Extrahepatic bile duct cancers occur in bile ducts outside the liver. There are two types of extrahepatic bile duct cancer:
- Perihilar bile duct cancer: This is the most common type of extrahepatic bile duct cancer. It accounts for 40 to 60% of all bile duct cancer cases. The disease occurs where the bile ducts exit the liver. It is sometimes called perihilar cholangiocarcinoma or a Klatskin tumor.
- Distal bile duct cancer: This disease starts in the part of the bile ducts that passes through the pancreas and connects with the small intestine. It makes up 20 to 40% of bile duct cancer cases.
Gallbladder cancer: A cancer that arises in the wall of the gallbladder. Gallbladder cancer is often found when looking for or doing surgery to remove gallstones.
Bile duct & gallbladder cancer risk factors
Anything that increases your chance of getting biliary cancer is a risk factor. Bile duct and gallbladder cancer risk factors include:
Age: Most cases of biliary cancer in the United States are diagnosed in people between the ages of 50 and 70.
Ethnicity: In the U.S., Native Americans are more likely to get biliary cancers.
Medical conditions: Having any of the following may increase your risk for biliary cancer:
- Primary sclerosing cholangitis (PSC): A progressive autoimmune disease which scars the bile ducts over time.
- Chronic liver diseases, including:
- Cirrhosis
- Bile duct stones
- Cholangitis
- Non-viral chronic liver disease
- Polycystic liver disease
- Hepatitis B or hepatitis C infection
- Inflammatory bowel diseases, including:
- Crohn’s disease
- Ulcerative colitis
- A history of bile duct cysts (choledochal) which are prone to chronic inflammation.
- Liver fluke infection: Liver flukes are parasites that are more common in South and Southeast Asia. Infection may arise due to the consumption of raw or undercooked fish.
- Exposure to thorotrast, a medical contrast agent that is no longer in use.
Smoking: Smoking increases the risk of many cancers, including bile duct cancer.
Excessive consumption of alcohol: Excessive consumption of alcohol likely increases the risk of biliary cancer. This is especially true for people who have alcohol-associated liver damage.
Family history: Several genetic disorders, including Lynch syndrome, may increase the risk of biliary tract cancers.
Learn more about bile duct cancer:
- Bile duct cancer symptoms
- Bile duct cancer diagnosis
- Bile duct cancer treatment
From 2006 to 2015, the incidence rate for liver and intrahepatic bile duct cancer increased by 32%, and the mortality rate increased by 25%.
U.S. Cancer Statistics Data Briefs, No. 5
November 2018
- In 2015, 32,908 new liver and intrahepatic bile duct cancer cases and 25,760 deaths were reported in the United States.
- From 2006 to 2015, the incidence rate increased by 32% (from 6.3 to 8.3 per 100,000 persons) and the mortality rate increased by 25% (from 5.3 to 6.6 per 100,000 persons).
- Persistent hepatitis B and hepatitis C infections are linked with liver cancer. Obesity, type 2 diabetes, drinking too much alcohol, and cigarette smoking can also lead to liver cancer.
Centers for Disease Control and Prevention. Liver and Intrahepatic Bile Duct Cancer, United States—2006–2015. USCS data brief, no 5. Atlanta, GA: Centers for Disease Control and Prevention. 2018.
Overview
What is cholangiocarcinoma?
Cholangiocarcinoma is a rare cancer that starts in your bile ducts. Bile ducts are thin tubes that bring bile (a fluid that helps you digest food) from your liver and gallbladder to your small intestine.
Most people receive a cholangiocarcinoma diagnosis after the cancer has already spread outside of their bile ducts. It’s difficult to treat and the prognosis (chance of recovery) is usually poor. However, a growing number of targeted therapies and clinical trials are starting to change that.
Are there different types of cholangiocarcinoma?
There are three types of cholangiocarcinoma:
- Extrahepatic cholangiocarcinoma is bile duct cancer outside the liver. Cancer may be in the ducts as they exit the liver, or in the ducts when they end in the small intestine. This is the most common type of bile duct cancer. A subset within extrahepatic cholangiocarcinoma is hilar cholangiocarcinoma, meaning a bile duct cancer that is outside the liver, but starts in the hilum, which is the area where the bile ducts and important blood vessels connect with the liver.
- Intrahepatic cholangiocarcinoma is bile duct cancer inside the liver. This should not be confused with liver cancer, which is more often referred to as hepatocellular carcinoma, or HCC.
- Gallbladder canceris cholangiocarcinoma that starts in the gallbladder.
Who is at risk of getting cholangiocarcinoma?
In the United States, Hispanic Americans are at a higher risk of cholangiocarcinoma. You may also be more likely to develop cholangiocarcinoma if you have:
- Abnormalities where the bile duct and pancreatic duct meet.
- Bile duct stones or choledochal cyst disease (bile duct cysts).
- Chronic ulcerative colitis.
- Cirrhosis of the liver.
- Clonorchiasis (infection with a Chinese liver fluke parasite).
- Hepatitis B or Hepatitis C.
- Human immunodeficiency virus (HIV).
- Inflammatory bowel disease (IBD).
- Non-alcohol related fatty liver disease.
- Primary sclerosing cholangitis (inflammation and scarring block the bile ducts).
Additional risk factors include:
- Alcohol use disorder.
- Diabetes.
- Exposure to toxins.
- Obesity.
- Smoking.
How common is cholangiocarcinoma?
Cholangiocarcinoma is rare. About 8,000 people in the U.S. develop this cancer each year. It’s most common in older people around age 70.
Symptoms and Causes
What causes cholangiocarcinoma?
Experts don’t know exactly what causes cholangiocarcinoma. The risk factors suggest that health conditions that cause chronic (long-term) inflammation in the bile ducts may play a role in the development of this cancer. Persistent damage like inflammation can also lead to DNA changes, which may change the way certain cells grow, divide and behave. These changes probably aren’t inherited, which means parents don’t pass them to their children. Instead, the changes likely happen during a person’s lifetime.
What are the symptoms of cholangiocarcinoma?
Bile duct cancer symptoms include:
- Abdominal pain.
- Dark urine.
- Fever.
- Itchy skin.
- Jaundice (skin and whites of eyes turn yellow).
- Light-colored stool.
- Nausea and vomiting.
- Unexplained weight loss.
Diagnosis and Tests
How is cholangiocarcinoma diagnosed?
Your healthcare provider evaluates your symptoms, reviews your medical history and does a physical exam. Tests for cholangiocarcinoma may include:
- Liver function tests: These liver tests check your blood for high levels of substances that might indicate your liver isn’t working as it should or there is a bile duct blockage, such as elevated liver enzymes.
- Tumor marker tests: These tests check your blood or urine for proteins and other substances that could mean you have cancer.
- Abdominal ultrasound: An abdominal ultrasound uses sound waves to create pictures of your liver, pancreas and gallbladder. This may be the first imaging exam you have if your healthcare provider suspects bile duct cancer.
- Magnetic resonance cholangiopancreatography (MRCP): MRCP is a specialized imaging exam that uses an MRI machine. It creates detailed pictures of the liver, bile ducts, gallbladder, pancreas and pancreatic duct.
- Endoscopic retrograde cholangiopancreatography (ERCP): ERCP uses an endoscope and a catheter (thin, flexible tubes) to examine your bile ducts. The endoscope goes into your mouth and down to your small intestine while you’re sedated (in a light sleep). The catheter delivers contrast dye to outline the shape of your bile ducts on X-rays. If you have a bile duct blockage, a stent device can be placed during an ERCP in the blocked bile duct to open it back up.
- Percutaneous transhepatic cholangiography (PTC): A PTC creates X-rays of your bile ducts like an ERCP. But instead of an endoscope and catheter, your healthcare provider delivers contrast dye by inserting a needle directly into your bile ducts and liver. A PTC is usually only for people who can’t have an ERCP.
If imaging and lab tests indicate cancer, your healthcare provider will perform a biopsy. A biopsy is a procedure to take a sample of tissue from your body. A pathologist examines the tissue under a microscope in a laboratory to check for cancer. Your healthcare provider can take bile duct tissue samples during an ERCP, PTC or by using a small needle through the skin.
How is cholangiocarcinoma staged?
A biopsy tells your healthcare provider if you have cancer, but it can also tell them the cancer’s stage. Staging is the process of finding out how much cancer is in your body. This information helps your healthcare provider plan treatment. For bile duct cancer, staging looks at the size of the tumor and whether cancer has spread from the bile ducts to the:
- Blood vessels.
- Lymph vessels and lymph nodes.
- Organs near the bile ducts, such as the liver or gallbladder.
- Distant organs, such as the lungs, bones or abdominal cavity (called the peritoneum).
Management and Treatment
How is cholangiocarcinoma treated?
Your treatment plan for cholangiocarcinoma depends on the location of the cancer and if it has spread. Surgery can treat early bile duct cancers that haven’t spread. But most bile duct cancers have spread by the time they’re diagnosed. In these cases, your healthcare provider may recommend a combination of multiple treatments.
How does surgery treat cholangiocarcinoma?
Your options for bile duct cancer surgery may include:
- Bile duct removal to get rid of part of the bile duct if the cancer hasn’t spread.
- Partial hepatectomy to remove part of the bile duct and sections of the liver.
- Whipple procedure to remove the bile duct, gallbladder and part of the pancreas, stomach and small intestine.
- Liver transplant to replace the liver with a donor liver, though this is only for early-stage cancers and it may be difficult to find a donor.
- Palliative surgery to ease symptoms of cancer by removing blockages in the bile duct. Your healthcare provider may place a stent (small, hollow tube) in your bile duct to help it drain into your small intestine or place a drain that connects to a bag outside your body.
How does radiation therapy treat cholangiocarcinoma?
Radiation therapy uses powerful beams of radiation to destroy tumors. You might receive radiation therapy after surgery to kill any remaining cancer cells. Or your healthcare provider may suggest it before surgery to shrink tumors before removing them. Radiation can also be delivered through transarterial radioembolization (TARE), which uses a catheter to implant tiny beads of radiation (often referred to as “Y90”) in the blood vessels supplying the tumor. The beads block the vessel to prevent blood from getting to the tumor. At the same time, the beads release radiation to shrink the tumor.
How does chemotherapy treat cholangiocarcinoma?
Chemotherapy (chemo) uses drugs to destroy cancer. Systemic chemotherapy that goes through your entire body can be used to shrink your tumor to make surgery possible. If the cancer is too advanced for surgery, chemotherapy is used to prolong life and reduce the symptoms of the cancer. In some cases, procedures can be done to deliver chemo directly to your bile duct:
- Transarterial chemoembolization (TACE), which uses a catheter to implant tiny beads of chemo in the blood vessels supplying the tumor. The beads block the vessel to prevent blood from getting to the tumor. At the same time, the beads release chemo medications to shrink the tumor.
- Hepatic artery infusion (HAI), which uses a surgically implanted pump to inject chemo directly into the main artery that brings blood to the liver. It’s controversial whether these are truly effective or not.
How does targeted therapy treat cholangiocarcinoma?
Targeted therapies target specific parts of cancer cells. Some people with bile duct cancer that’s the result of an abnormal gene have specific proteins on their cancer cells. Targeted therapies can attack these cells to keep them from dividing.
How does immunotherapy treat cholangiocarcinoma?
Immunotherapy helps your body’s own immune system fight cancer. In bile duct cancer, some cancer cells contain a protein that prevents immune cells from attacking the cancer. Immunotherapy disables the proteins so immune cells can do their job better.
Prevention
How can I prevent cholangiocarcinoma?
There’s no way to completely prevent bile duct cancer, but you may be able to reduce your risk by:
- Avoiding viruses such as hepatitis B, hepatitis C and HIV.
- Getting vaccinated against hepatitis B.
- Limiting the amount of alcohol you drink.
- Maintaining a healthy body weight.
- Quitting smoking.
Outlook / Prognosis
What is the prognosis for people with cholangiocarcinoma?
The outlook (prognosis) for people with cholangiocarcinoma is usually poor. The five-year survival rate for bile duct cancer that hasn’t spread outside of the bile ducts is 10% to 15%. This rate drops to 2% if the cancer spreads to areas of the body that are far from the bile ducts, such as the lungs. But newer treatments mean these rates will improve over time.
Living With
What should I ask my healthcare provider?
If you have cholangiocarcinoma, you may want to ask your healthcare provider the following questions:
- What stage is the cancer?
- Are there clinical trials I can take part in?
- Can the cancer come back after treatment?
- Will the treatment have side effects?
- Is there anything I can do to make treatment more effective?
A note from Cleveland Clinic
Cholangiocarcinoma is cancer of the bile ducts. It’s a rare disease that’s more common in older people. You have a higher risk of cholangiocarcinoma if you have certain viruses or chronic inflammation in your bile ducts or liver. This type of cancer usually requires a combination of treatments including surgery, radiation therapy or chemotherapy.