What Is Bile Duct Cancer?

In This Article

Bile duct cancer, also known as cholangiocarcinoma, is a rare type of cancer that affects the bile ducts—thin tubes that run from the liver and gallbladder to the small intestine. Because of where these ducts are situated, cholangiocarcinoma can manifest acute hepatitis symptoms, including abdominal pain, changes in stool color, and the yellowing of the eyes and skin.

Bile duct cancer typically affects older adults and is linked to inflammatory bowel diseases, liver disease, and congenital liver or bile duct abnormalities. This cancer is most often incurable, in part because symptoms tend to develop when the malignancy has already spread (metastasized).

Anatomy of Biliary Duct System

Your network of bile ducts starts in the liver where numerous small tubes collect bile, a fluid that aids in digestion.

These smaller ducts come together to form the right and left hepatic ducts, which then combine outside of the liver into the common hepatic duct.

Lower down, the common hepatic duct connects to the cystic duct of the gallbladder (where bile is stored) and conjoin into the common bile duct.

Bile duct cancer can develop in any part of this network of tubes.

Types of Bile Duct Cancer

Based on the location of the tumor, the malignancy can be classified in one of three ways:

  • Intrahepatic bile duct cancer: These cancers start in the smaller bile branches inside the liver.
  • Perihilar bile duct cancer: These cancers start in the hepatic hilum, the area in which the left and right hepatic ducts have conjoined and are just starting to leave the liver.
  • Distal bile duct cancer: These cancers are found further down the bile duct near the small intestine.

Bile duct cancers that develop within the liver are also referred to as intrahepatic bile duct cancers, while those that develop outside of the liver are referred to as extrahepatic bile duct cancers.

Bile Duct Cancer Symptoms

Because of their location in or near the liver, bile duct cancer can cause liver inflammation, more commonly referred to as hepatitis. This can cause an abnormal increase in liver enzymes and the accumulation of bilirubin (a yellowing pigment caused by the breakdown of red blood cells) in the bloodstream.

Symptoms of bile duct cancer are consistent with that of hepatitis and may include:

  • Abdominal pain in the upper right quadrant just under the ribs
  • Hepatomegaly (abnormally enlarged liver)
  • Jaundice (yellowing of the skin and eyes)
  • Fever
  • Chalky stools
  • Dark, cola-colored urine
  • Generalized itching
  • Fatigue
  • Nausea
  • Loss of appetite

Unintentional weight loss, a symptom consistent with both acute hepatitis and cancer in general, is common in people with bile duct cancer.

The severity of symptoms typically corresponds to the location of the tumor. Extrahepatic tumors tend to present with jaundice more that intrahepatic ones due to the increased obstruction of fluids exiting the liver. Extrahepatic tumors tend to manifest with more overt liver pain and swelling.

Causes

According to the American Cancer Society, around 8,000 people are diagnosed with bile duct cancer in the United States each year. The average age of diagnosis for intrahepatic and extrahepatic bile duct cancer is 70 and 72, respectively.

There are numerous diseases and disorders linked to the onset of bile duct cancer, the most common being:

Risk Factors

Certain groups of people are also at greater risk of bile duct cancer. For reasons not entirely clear, Latinx individuals are more likely to get the disease than another groups in the United States.

A family history of cholangiocarcinoma may also increase your risk, although the disease itself is not considered an inheritable one. In many cases, the underlying causes of bile duct cancer is never be found.

Obesity is also believed to play a key role, in large part because of extreme inflammatory stress it places on the liver. The same applies to smoking and excessive alcohol use. Unlike other risk factors, these are considered modifiable and may potentially reduce a person's risk of bile duct cancer if healthier habits (weight loss, smoking cessation, reduced alcohol intake) are embraced.

Diagnosis

Bile duct cancer is diagnosed with a combination of a physical exam, blood tests, imaging studies, and minimally invasive medical procedures. Ultimately, the only way to definitively confirm the disease is with a biopsy of affected tissues.

In addition to identifying the symptoms of the disease during the physical exam, your doctor will also take into account your personal risk factors for the disease. Based on the initial assessment, they will order a series of tests and procedures to help root out the cause.

Blood Tests

There are two blood tests commonly used in the diagnosis of bile duct cancer. Neither is able to diagnose the disease, but they can point the doctor in the right direction and support the initial diagnosis.

The first is a liver function test (LFT), a generalized panel of tests that can detect if liver enzymes are raised due to liver inflammation. Excessively high liver enzymes are a general sign of liver disease but are not specifically indicative of cancer itself.

If cancer is suspected, there are also tumor marker testscarcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (19-9)—that measure the levels of protein in the blood that are produced in response to gastrointestinal cancers. Again, these tests cannot definitively identify bile duct cancer but get doctors closer to the correct diagnosis.

Imaging Tests

Imaging tests can help diagnose bile duct cancer by indirectly visualizing the tumor and surrounding structures. There are different tests a doctor can order:

  • Abdominal ultrasound, a non-invasive procedure that uses high-frequency sound waves to generate images of abdominal organs and structures
  • Computed tomography (CT scan), in which multiple X-rays are used to create three-dimensional "slices" of internal organs
  • Magnetic resonance imaging (MRI scan), in which powerful magnetic and radio waves create highly detailed images of internal organs, especially soft tissues
  • MRI cholangiopancreatography, a specialized MRI technique using contrast dyes to detect blockages and other problems in the bile ducts, gallbladder, liver, or pancreas

Procedures

There are a number of minimally invasive procedures that can help doctors access tumors and obtain tissue samples (biopsies) for evaluation in the lab. Among the procedures commonly used are:

  • Endoscopic retrograde cholangiopancreatography (ERCP): A flexible tube called an endoscope is passed through the mouth into the small intestine to visualize, access, and obtain tissues from the larger bile ducts.
  • Percutaneous transhepatic cholangiography (PTC): A needle is inserted through the abdomen to access tumors in the bile duct.
  • Endoscopic ultrasound: A specialized ultrasound transducer is introduced into the mouth or rectum to access the small intestine to obtain tissue samples from the bile ducts.
  • Laparoscopy: A minimally invasive surgery in which several small incisions are made in the abdomen to access a tumor using specialized surgical equipment.

In addition to being able to definitively confirm bile duct cancer, the tissue sample taken during a biopsy can also be used to stage the malignancy and determine the appropriate course of treatment.

Staging

Once bile duct cancer has been definitively diagnosed, the doctor will order an additional round of tests to stage the disease.

This may involve imaging studies such as positron emission tomography (PET) which uses radioactive dyes to identify changes in metabolism consistent with cancer. This can establish if the disease is localized (contained with no signs of spread), regional (affecting nearby tissues), or distant (metastatic).

Although intrahepatic and extrahepatic bile duct cancer are both staged in five parts (stages 0 to 4), there are variations what defines each of them.

Bile Duct Cancer Stages by Location
Stage Type Definition
0 Intrahepatic Abnormal cells found in intrahepatic bile ducts that have the potential to turn cancerous (a.k.a. carcinoma in situ)
  Extrahepatic Abnormal cells found in the perihilar or distal bile duct that have the potential to turn cancerous
1 Intrahepatic Cancer confined to the intrahepatic bile ducts that are 5 centimeters (cm) or smaller (stage IA) or larger than 5 cm (stage IB)
  Extrahepatic Cancer confined to the innermost layers of the perihilar or distal bile duct
2 Intrahepatic Cancer that has spread through the wall of an intrahepatic duct and into nearby blood vessels only
  Extrahepatic Cancer that has spread through the wall of the perihistal or distal duct and is found in nearby fatty tissues or liver tissues
3 Intrahepatic Cancer that has spread to the outside of the liver (stage IIIA), into the liver itself (stage IIIB), or to nearby organs or lymph nodes (stage IIC)
  Extrahepatic Cancer that has spread to one side of the portal vein or hepatic artery of the liver (stage IIIA), to both sides of these blood vessels or to intrahepatic bile ducts (stage IIIB), or to one to three nearby lymph nodes (stage IIIC)
4 Intrahepatic Cancer that has spread to distant organs, most commonly the lungs, brain, bone, and lining of the abdomen
  Extrahepatic Cancer that has spread to four or more lymph nodes (stage IVA) or distant organs (stage IVB)

Genetic Profiling

In addition to the staging of cancer, genetic testing may be performed to see if your cancer has what are considered treatable mutations. If so, you may be a candidate for newer targeted therapies that specifically recognize and kill these cancer cells.

Treatment

The majority of bile duct cancers are incurable, mainly because the disease is typically advanced by the time that overt symptoms appear.

With that said, bile duct cancer is sometimes caught early before metastasis has occurred and can be treated with surgery. This is typically followed by adjuvant (secondary supportive) therapies to destroy all remaining cancer cells.

When the tumor and affected tissue cannot be removed in their entirety, treatment is focused on slowing the spread of cancer, reducing symptoms, extending survival, and improving overall quality of life.

Overview of Treatment Options
Surgery Adjuvant Therapy Palliative Care
Hepatectomy with lymph node resection (intrahepatic) External radiation therapy Pain medications
Whipple procedure with extrahepatic bile duct resections (extrahepatic) Internal radiation therapy Palliative radiation therapy
Liver transplant (inoperable intrahepatic) Adjuvant chemotherapy Palliative radiation therapy
Biliary bypass (palliative surgery)   Targeted therapies
    Immunotherapy
    Biliary stenting
    Percutaneous tumor ablation
    Percutaneous ethanol injection
    Clinical trials

Surgery

Unless the cancer is advanced and clearly inoperable, most people will undergo exploratory surgery to determine if surgical resection (removal) is possible. This is usually performed with laparoscopy rather than open surgery.

If the tumor is localized or regional (stages 1 through 3) with no evidence of metastasis, resection may be considered based on the general health of the individual and the function of the liver.

The types of surgery used can vary by the location of the tumor:

  • Intrahepatic bile duct cancers typically require the surgical removal of part of the liver (hepatectomy) along with resection of nearby lymph nodes.
  • Extrahepatic bile duct cancers are commonly treated with en bloc pancreatoduodenectomy (also known as the Whipple procedure), which involves the removal of the common bile duct along with a portion of the pancreas and small intestine. The affected extrahepatic bile duct would also be resected.

Some early-stage intrahepatic tumors are inoperable but can still be treated with a liver transplant. In such cases, chemotherapy and radiation may be used to halt the spread of disease until a donor liver can be found.

Adjuvant Therapies

Adjuvant therapies are used after surgery with the intent of curing the disease and preventing its return. This may include chemotherapy and external or internal radiation therapies commonly used to treat cancer.

With that said, it is unclear how effective these therapies are in preventing recurrence, and there is considerable controversy as to their appropriate use.

Part of the controversy stems from the fact that so few people with bile duct cancer have operable tumors. Those that do may or may not respond to these therapies.

At present, there is no evidence that either adjuvant chemotherapy or radiation therapy can extend survival times, even in people with early-stage malignancies. Even so, doctors often recommend adjuvant therapy, particularly if there is any chance that cancer cells are remaining after surgery.

Palliative Therapy

Palliative therapy is a form of treatment used to alleviate pain and control for symptoms of late-stage disease. In people with inoperable bile duct cancer, this can take several forms:

  • Pain medications, including opioid drugs such as fentanyl
  • Palliative radiation therapy, which is primarily used to reduce the size of a tumor to unblock a bile duct or reduce pressure on compressed nerves
  • Palliative chemotherapy delivered via a catheter in a blood vessel to the blocked bile duct to shrink the tumor
  • Biliary stenting involving the placement of a tube, called a stent, in a bile duct to improve biliary flow
  • Biliary bypass, a surgical procedure in which the bile duct obstruction is resected and the cut ends are sewn together
  • Percutaneous tumor ablation, in which heat or electrical energy is delivered to the tumor via a needle-like electrode inserted through the skin
  • Percutaneous ethanol injections, in which alcohol is injected into the tumor to shrink it and deaden the nerves that relay pain

Newer targeted therapies and immunotherapies being used in people whose cancer has specific genetic mutations include:

  • The targeted drugs Tibsovo (ivosidenib) and Pemazyre (pemiganitib), which can stem the growth of cancer
  • Immunotherapeutic agents like Keytruda (pembrolizumab), which can slow disease progression

People diagnosed with bile duct cancer are encouraged to participate in clinical trials. This can provide them access to experimental drugs or therapies that may improve outcomes, particularly if their disease is inoperable.

Prognosis

Five-year survival is a common measure used to determine what percentage of people with a disease will be alive at least five years following the initial diagnosis. The five-year survival rate for bile duct cancer is broken down by how far cancer has spread and whether the tumor is intrahepatic or extrahepatic.

Generally speaking, people with extrahepatic bile duct cancer have better outcomes (prognoses) because the liver is less likely to be affected. Metastatic liver involvement with any type of cancer is linked to poorer outcomes.

Bile Duct Cancer 5-Year Survival Rates by Location
  Intrahepatic Extrahepatic
Localized 15% 30%
Regional 6% 24%
Distant 2% 2%

A Word From Verywell

Learning that you have bile duct cancer can lead you to assume that you only have a short time to live. It is important to remember that the disease can vary from one person to the next and that the five-year survival estimates are just that—estimates. Some people can survive longer based on their general health and the location of the tumor.

Before jumping to any conclusions, work with your doctor to properly stage the disease, and seek support from friends and loved ones to help overcome stress and anxiety. If you are unsure about the diagnosis or a recommended therapy, do not hesitate to seek a second opinion from an oncologist specializing in biliary cancers.

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