Canadian Cancer Society logo

Bile duct cancer

You are here: 

Intrahepatic bile duct cancer

Intrahepatic bile duct cancer starts in the bile ducts inside the liver. Intrahepatic bile duct cancer is the least common type of bile duct cancer and accounts for about 5%–10% of all bile duct cancers. Intrahepatic bile duct cancers are uncommon tumours.

Cholangiocarcinoma is another term used to describe intrahepatic bile duct cancer (intrahepatic cholangiocarcinoma or ICC). Intrahepatic bile duct cancers differ from extrahepatic bile duct cancer in the following areas:

  • risk factors
  • subtypes of tumours
  • staging
  • prognosis and treatment

Risks

Risk factors increase a person’s chance of developing intrahepatic bile duct cancer. The factors that increase the risk of developing intrahepatic bile duct cancer include:

  • parasitic infections – liver fluke infection with Clonorchis sinensis (C. sinensis) and Opisthorchis viverrini (O. viverrini)
  • hepatitis C infection – plays more of a role in intrahepatic bile duct cancers than extrahepatic bile duct cancers
  • intrahepatic bile duct stones (hepatolithiasis) – can cause chronic inflammation of the bile ducts inside the liver
  • primary sclerosing cholangitis (PSC) – causes inflammation of the bile duct (cholangitis) that leads to scar tissue (sclerosis)
  • cirrhosis of the liver – scarring of the liver tissue

Intrahepatic bile duct cancers are more common in Asian countries. The incidence of intrahepatic bile duct cancer has been increasing worldwide, while the incidence of extrahepatic bile duct cancer has remained constant. This suggests that different risk factors may be involved for these cancers.

Back to top

Early detection

Early detection means finding a cancer or precancerous condition at an early stage. In most cases, finding cancer early increases the chances of successful treatment.

Recognizing symptoms and getting regular checkups are the best ways to detect intrahepatic bile duct cancer early. The sooner symptoms are reported, the sooner a doctor can diagnose and treat the cancer.

Back to top

Signs and symptoms

A sign is something that can be observed and recognized by a doctor or healthcare professional (for example, a rash). A symptom is something that only the person experiencing it can feel and know (for example, pain or tiredness). Intrahepatic bile duct cancer does not have many warning signs in its early stages. Symptoms usually develop as the cancer grows and advances. Other health conditions can have the same signs and symptoms, and having them doesn’t necessarily mean a person has cancer. It is important to see a doctor about any of the following:

  • painless jaundicejaundiceA condition in which the skin and whites of the eyes become yellow and urine is dark yellow.
    • Jaundice occurs if the main intrahepatic bile ducts become narrowed or blocked by the tumour, so jaundice does not often appear until the cancer is advanced.
  • discomfort
    • This symptom occurs when the tumour becomes large enough to cause pain.
  • lump or mass in the abdomen that can be felt
    • A large mass may be present at diagnosis because the tumour does not cause symptoms in its early stages.
  • fatigue
  • loss of appetite
  • weight loss

Back to top

Diagnosis

Diagnosis is the process of finding the underlying cause of a health problem. Intrahepatic bile duct cancer is usually not diagnosed until it is at an advanced stage. An intrahepatic bile duct cancer may be discovered by accident when imaging studies are done to diagnose another health problem.

Many of the same tests used to initially diagnose cancer are also used to determine the stage (how far the cancer has progressed). The tests used for intrahepatic bile duct cancer are similar to the tests used to diagnose and stage extrahepatic bile duct cancer. Tests may include:

  • medical history and physical examination
  • blood chemistry tests
  • tumour marker tests
  • ultrasound
  • computed tomography (CT) scan
  • magnetic resonance imaging (MRI)
  • magnetic resonance cholangiopancreatography (MRCP)
  • endoscopic retrograde cholangiopancreatography (ERCP)
  • percutaneous transhepatic cholangiography (PTC)

Find out more about tests used to diagnose and stage bile duct cancer.

Back to top

Pathology and staging

Pathology refers to the careful examination of tissue under a microscope in order to find out whether it's cancerous or non-cancerous and to determine the type of tumour it is. Different types of tumours can affect the bile ducts.

Intrahepatic cholangiocarcinoma start in the epithelialepithelialA thin layer of epithelial cells that makes up the outer surfaces of the body (the skin) and lines hollow organs, glands and all passages of the respiratory, digestive, reproductive and urinary systems. lining of the intrahepatic bile ducts. It accounts for 15%–20% of all primary liver cancers. It can occur anywhere along the intrahepatic bile duct.

It can be difficult to tell an intrahepatic bile duct cancer from cancer that starts in the cells of the liver (primary hepatocellular carcinoma or HCC). One way to tell them apart is that intrahepatic bile duct cancers can produce mucin (a protein substance found in mucus), while hepatocellular carcinoma do not typically produce mucin. Intrahepatic bile duct cancers and hepatocellular carcinoma are often treated the same way.

Intrahepatic bile duct cancer often presents as a large tumour or solid mass. The tumour spreads along the duct to the liver and blood vessels of the liver.

Types of intrahepatic bile duct cancer

The 3 main types of intrahepatic bile duct tumours are:

  • intrahepatic cholangiocarcinoma
    • also called ductular cholangiocarcinoma, peripheral cholangiocarcinoma
    • often associated with hepatitis C infection
  • combined hepatocellular and cholangiocarcinoma
    • also called mixed hepatocellular carcinoma/cholangiocarcinoma
    • has characteristics of both hepatocellular carcinoma and intrahepatic bile duct cancer
    • often associated with hepatitis C and hepatitis B infection and cirrhosis of the liver
  • bile duct cystadenocarcinoma
    • appears as a cyst in the intrahepatic bile duct or liver

Grades of intrahepatic bile duct cancer

Grading is a way of classifying intrahepatic bile duct cancer cells based on their appearance and behaviour when viewed under a microscope. To find out the grade of a tumour, the biopsy sample is examined under a microscope. A grade is given based on how the cancer cells look and behave compared with normal cells (differentiation). Intrahepatic bile duct tumours tend to be:

  • well differentiated – slow growing, less likely to spread
  • moderately well differentiated or moderate grade

Stages of intrahepatic bile duct cancer

Staging is a way of describing or classifying a cancer based on the extent of cancer in the body. The most common staging system for intrahepatic bile cancer is the TNM system. The International Union Against Cancer (UICC) uses the TNM system to describe the extent of many solid tumour cancers.

Intrahepatic bile duct cancer has a different staging system than extrahepatic bile duct cancers.

TNM

TNM stands for tumour, nodes, metastasis. TNM staging describes:

  • the size and extent of the primary tumour
  • the number and location of any regional lymph nodes that have cancer cells in them
  • whether the cancer has spread or metastasized to another part of the body

Primary tumour (T)

TX

Primary tumour cannot be assessed

T0

No evidence of primary tumour

Tis

Carcinoma in situCarcinoma in situA very early stage of cancer in which tumour cells have not yet invaded surrounding tissues. (intraductal tumour with cancer cells growing only in the innermost layer of the bile duct)

T1

A single tumour that has not grown into any nearby blood vessels.

T2a

A single tumour that has spread to nearby blood vessels.

T2b

Multiple tumours, with or without spread to the blood vessels.

T3

The tumour has either grown into the membrane that covers most of the abdominal organs (visceral peritoneum) or grown directly into nearby (adjacent) structures outside the liver (extrahepatic structures).

T4

The tumour has spread through the walls of the bile duct (periductal invasion) and has grown along the length of the intrahepatic bile duct (periductal growth pattern).

Regional lymph nodes (N)

NX

Regional lymph nodes cannot be assessed

N0

No regional lymph node metastasis

N1

Regional lymph node metastasis

Lymph node involvement for intrahepatic bile duct cancer varies with location in the liver.

  • For intrahepatic bile duct cancer in the right lobe of the liver, the regional lymph nodes include nodes around the:
    • common bile duct
    • hepatic arteries
    • portal vein and cystic duct (hilar lymph nodes)
    • duodenum (periduodenal lymph nodes)
    • pancreas (peripancreatic lymph nodes)
  • For intrahepatic bile duct cancer in the left lobe of the liver, the regional lymph nodes include the nodes around the:
    • portal vein and cystic duct (hilar lymph nodes)
    • stomach and liver (gastrohepatic lymph nodes)

Distant metastasis (M)

M0

No distant metastasis

M1

Distant metastasis

Distant metastasis (M1) includes spread to the:

  • celiac lymph nodes (lymph nodes in the abdomen that drain lymph from the stomach, duodenum, pancreas, spleen and biliary tract)
  • periaortic lymph nodes (lymph nodes around the aorta)
  • caval lymph nodes (lymph nodes around the inferior vena cava).

Stage grouping for intrahepatic bile duct cancer

The UICC further groups the TNM data into the stages listed in the table below.

UICC staging – intrahepatic bile duct cancer
UICC stageTNMExplanation

stage I

T1

N0

M0

A single tumour that has not grown into any nearby blood vessels.

The cancer has not spread to the lymph nodes or distant sites.

stage II

T2

N0

M0

The cancer is either:

  • A single tumour that has grown into nearby blood vessels.
  • Two or more (multiple) tumours, which may or may not have grown into nearby blood vessels.

The cancer has not spread to the lymph nodes or distant sites.

stage III

T3

N0

M0

The tumour has either grown into the membrane that covers most of the abdominal organs (visceral peritoneum) or has grown directly into nearby structures outside the liver, such as the duodenum, stomach, common bile duct, colon, abdominal wall and diaphragm.

The cancer has not spread to the lymph nodes or distant sites.

stage IVA

T4

N0

M0

The tumour has spread through the walls of the bile duct (periductal invasion) and has grown along the length of the intrahepatic bile duct (periductal growth pattern).

The cancer has not spread to the lymph nodes or distant sites.

any T

N1

M0

The tumour is any size.

The cancer has spread to the lymph nodes, but has not spread to distant sites.

stage IVB

any T

any N

M1

The tumour is any size.

The cancer may or may not have spread to the lymph nodes.

Cancer has spread to distant sites.

Recurrent intrahepatic bile cancer

Recurrent intrahepatic bile cancer means that the cancer has come back after it has been treated. It may recur in the same location as the original cancer or it may recur in another part of the body (metastatic intrahepatic bile duct cancer).

Prognosis and survival

People with intrahepatic bile duct cancer may have questions about their prognosis and survival. Prognosis and survival depend on many factors. Only a doctor familiar with a person’s medical history, type of cancer, stage, characteristics of the cancer, treatments chosen and response to treatment can put all of this information together with survival statistics to arrive at a prognosis.

Prognosis

A prognosis is the doctor’s best estimate of how cancer will affect a person, and how it will respond to treatment. The prognosis for people with intrahepatic bile duct cancer depends on:

  • the extent (stage of the tumour)
    • Prognosis is somewhat better for people with early stage cancer than for people with advanced stage cancer.
    • People with multiple tumours, larger tumours and tumours that have spread to nearby blood vessels or lymph nodes tend to have a poor outcome.
  • resectability
    • Tumours that can be completely removed by surgery (resectable) have a more favourable prognosis than tumours that cannot be removed by surgery (unresectable).
  • surgical margins
    • Clear surgical margins (no cancer cells in the healthy tissue around the tumour removed during surgery) improves prognosis.

Survival

Cancer survival statistics are very general estimates and must be interpreted very carefully. Because survival statistics are based on the experience of groups of people in the general population, they cannot be used to predict a particular person’s chances of survival.

There are no specific Canadian statistics available for the different stages of intrahepatic bile duct cancer. The following information comes from a variety of sources and may include statistics from other countries.

Survival for intrahepatic bile duct cancer may be grouped according to the extent of the tumour.

Intrahepatic bile duct cancer survival
Group5-year relative survival

localized (includes stage I tumours)

15%

regional (includes stage II and III tumours)

6%

distant (includes stage IV tumours)

2%

The median survival of people with resectable intrahepatic bile duct cancer ranges from 12–59 months. Median survival is the period of time (usually months or years) at which half of the people with cancer are still alive. The other half will live less than this amount of time.

Back to top

Treatment

Each person with intrahepatic bile duct cancer will have a treatment plan designed for them by their healthcare team. The team will recommend treatment options based on the specific characteristics of the cancer and the unique needs of the person. Intrahepatic bile duct cancers are treated like a primary liver (hepatocellular) carcinoma. A treatment plan for intrahepatic bile duct cancer may include one or more of the following:

Surgery

Complete surgical removal (resection) of the cancer offers the best outcome.

  • Surgery involves removing the lobe of the liver or segment of the liver along the bile duct where the tumour is located. This often involves doing a liver resection (partial hepatectomy).
    • The amount of liver tissue removed is determined by the location of the tumour and the extent of liver tissue involved.
    • Sometimes a whole lobe of the liver must be removed (hepatic lobectomy).
  • Surgical resection with negative surgical margins (no cancer cells in any of the normal tissue that is removed with the tumour) is the most important factor in achieving long-term survival.
  • The removal of lymph nodes during surgery for intrahepatic bile duct is not routinely done. It is controversial because removing the lymph nodes does not seem to improve the person’s outcome.

Many people with intrahepatic bile duct cancer cannot have surgery because their cancer is too advanced and they are in poor health when they are diagnosed. Surgery to completely remove the tumour isn’t an option (the cancer is unresectable) if there is cancer:

  • throughout both lobes of the liver or outside the liver
  • in the blood vessels of the liver such as the hepatic artery or portal vein
  • in the lymph nodes or distant sites (metastatic disease)

Intrahepatic bile duct cancers tend to recur after surgery, but there is no established role for additional (adjuvant) therapy after surgery. However, the following additional treatments may be offered if cancer cells remain after surgery has been done (residual disease):

  • more surgery
  • chemotherapy
  • chemotherapy combined with radiation therapy (chemoradiation)
  • radiation therapy alone
  • chemoembolization
  • hepatic artery radioembolization with Yttrium-90

A liver transplant is usually not an option for most people with intrahepatic bile duct cancer because of the high recurrence rate and rapid spread (metastases) of these tumours.

Chemotherapy

Chemotherapy may be offered for people whose cancer cannot be removed by surgery (unresectable disease) or with metastatic disease, if they are well enough to tolerate the treatment. Chemotherapy drugs may be used alone or in combination. The most common chemotherapy drugs used to treat intrahepatic bile duct cancer are the same as those used to treat extrahepatic bile duct cancer:

  • 5-fluorouracil (5-FU, Adrucil)
  • gemcitabine (Gemzar)
  • capecitabine (Xeloda)
  • cisplatin (Platinol AQ)

For some people with unresectable bile duct cancer, chemotherapy drugs may be used to make the cancer cells more sensitive to the effects of radiation therapy. These drugs are called radiosensitizers. Giving radiation therapy and chemotherapy together is called chemoradiation.

For more detailed information on specific drugs, go to sources of drug information.

Radiation therapy

External beam radiation therapy or brachytherapy (internal radiation therapy) may be used for both intrahepatic and extrahepatic bile duct cancers. Radiation therapy may be used to:

  • treat unresectable intrahepatic bile duct cancer
  • relieve pain or to control the symptoms of advanced intrahepatic bile duct cancer (palliative radiation therapy)
  • control localized intrahepatic bile duct cancer

Palliative surgery or procedures

Sometimes the person with intrahepatic bile duct cancer is not well enough to have an operation or doctors think that the cancer cannot be removed by surgery. In these cases, treatment is aimed at relieving signs and symptoms, such as:

  • jaundice – occurs when cancer blocks the bile duct and stops the flow of bile
  • pain and inflammation of the bile ducts (cholangitis) – caused by a tumour blocking the bile duct
  • abdominal pain – caused by cancer in the liver or other organs or structures in the abdomen

Palliative surgery or procedures may include:

  • placing a small wire or plastic tube (stent) to keep the bile duct open and drain the liver
  • inserting a tube (catheter) to help drain bile
  • doing a biliary bypass to change the flow of bile

Clinical trials

Clinical trials investigate better ways to prevent, detect and treat cancer. There are some clinical trials in Canada that are open to people with intrahepatic bile duct cancer. Bile duct cancer trials may be included in trials for:

  • liver cancer
  • gallbladder cancer
  • other gastrointestinal cancers
  • advanced or metastatic cancer

For more information, go to clinical trials.

Follow-up

Because intrahepatic bile duct cancer is so rare, there are no standard guidelines for follow-up care. Follow-up after treatment is tailored to the individual. Regular follow-up is done if the person had surgery.

Intrahepatic bile duct cancers are treated like a primary liver (hepatocellular) carcinoma. Find out more about treatment options for liver cancer and their side effects.

Back to top

Supportive care

A cancer diagnosis can lead to many challenges for people with cancer and their families. Each person’s experience will be different because their cancer, treatment and recovery are different. A person with intrahepatic bile duct cancer may have concerns about:

  • pain
    • Pain can occur with intrahepatic bile duct cancer or its treatment.
    • People with intrahepatic bile duct cancer may experience pain because the tumour grows into surrounding nerves and organs, such as the liver.
    • The tumour can also block the bile duct and prevent bile from draining properly.
  • jaundice
    • When a bile duct tumour blocks (obstructs) the bile duct or spreads (metastasizes) to the liver, then bile cannot drain properly.
    • As bile builds up in the blood and the skin, it causes jaundice.
  • loss of appetite
    • Many people with intrahepatic bile duct cancer will have advanced disease when they are diagnosed. As the cancer progresses, people can lose their appetite and their diet and nutrition may be poor.
    • Loss of appetite can cause a person to lose weight.
    • Nausea and vomiting can also occur in people with intrahepatic bile duct cancer and affect appetite.
  • liver failure
    • Liver failure can occur when the bile ducts are blocked.
    • Jaundice, abnormal liver function tests, bleeding or abdominal pain or swelling can indicate liver failure.
    • Supportive measures are used to make the person as comfortable as possible, including trying to relieve the blockage.
  • coping with advanced bile duct cancer
    • People with advanced intrahepatic bile duct cancer are offered palliative care. This is a special type of care that focuses on:
      • making the person as comfortable as possible
      • relieving symptoms
      • providing support
      • improving or maintaining the person’s quality of life.

Intrahepatic bile duct cancers are treated like a primary liver (hepatocellular) carcinoma. Find out more about supportive care for liver cancer, including information about recovery and coping after treatment.

Back to top

Stories

Dr Steven Jones Using cancer genetics to guide personalized treatment

Read more

Help for smokers trying to quit

Illustration of no smoking symbol

It’s okay to need help to quit smoking. The Canadian Cancer Society is here to support people who are ready to quit and even those people who aren’t ready.

Learn more