Bile Duct Cancer Causes and Treatment

Bile duct cancer, also known as cholangiocarcinoma, is a rare type of cancer that affects the bile ducts—the thin tubes in the digestive system that run from the liver and gallbladder to the small intestine.

This cancer is usually incurable, in part because symptoms usually develop after the tumor has already spread. About 10% of people survive five years or more after diagnosis.

This article covers the symptoms and causes of bile duct cancer. You will also learn how the disease is diagnosed and treated, and what lifestyle changes could help lower your risk.

Types of Bile Duct Cancer

The biliary system is a network of organs and ducts that produce, store, and transport a digestive fluid called bile. This includes the liver which produces bile and the gallbladder which stores and releases bile when needed.

The system starts with the right and left hepatic ducts inside the liver that join to form the common hepatic duct outside the liver. The common hepatic duct then connects to the cystic duct extending from the gallbladder to form the common bile duct that delivers bile to the small intestine.

Bile duct cancers are broadly categorized by where tumors form within this system:

• Intrahepatic bile duct cancers involve tumors in the smaller bile ducts inside the liver.
• Extrahepatic bile duct cancers involve tumors at the junction of the common hepatic duct and left and right hepatic ducts (called perihilar bile duct cancers) and those further down the biliary system (called distal bile duct cancers),

What Are Common Symptoms of Bile Duct Cancer?

Bile duct cancer can cause hepatitis, which is inflammation of the liver. This leads to increased blood levels of bilirubin, a yellow pigment produced by the breakdown of red blood cells. In general, symptoms of bile duct cancer may not appear until the cancer is in a late stage.

These can include:

• Jaundice (yellowing of the skin and eyes)
• Abdominal pain just under the ribs
• Fever
• Chalky stools
• Dark, cola-colored urine
• Itchy skin
• Fatigue
• Nausea
• Loss of appetite
• Unintentional weight loss

The severity of symptoms typically depends on the location of the tumor. Tumors that develop outside the liver are likely to cause jaundice, itchy skin, dark urine, and abdominal pain. In some cases, tumors inside the liver may not cause symptoms at all.

Causes and Risk Factors of Bile Duct Cancer

The cause of bile duct cancer is unknown, but there are risk factors associated with this rare form of cancer affecting roughly 8,000 people in the United States each year.

Risk factors for bile duct cancer include:

• Being over 70
• A family history of bile duct cancer
• Obesity
• Smoking
• Excessive alcohol use

There are also numerous diseases and disorders linked to bile duct cancer, including:

• Primary sclerosing cholangitis: An inflammatory bile duct disease thought to be autoimmune
• Inflammatory bowel disease (IBD): Including ulcerative colitis and Crohn's disease
• Chronic liver disease: Including cirrhosis, hepatitis B, hepatitis C, and fatty liver disease
• Choledochal cysts: Noncancerous growths in bile ducts that block the flow of bile
• Liver parasites: Including liver fluke common in Asia and the developing world
• Congenital disorders: Like Lynch syndrome II and polycystic liver disease
  

How Is Bile Duct Cancer Diagnosed and Staged?

If your healthcare provider is concerned that you could have bile duct cancer, you will have a medical history and physical examination. From there, they may order blood tests, imaging studies, and other procedures to determine the cause of your symptoms.

A diagnosis of bile duct cancer is confirmed with a biopsy.

Blood Tests

Blood tests used to diagnose bile duct cancer include:

• Liver function tests (LFTs): These measure liver enzymes that are characteristically elevated when cancer is involved.
• Tumor marker tests: These detect proteins like carcinoembryonic antigen (CEA) that are increased when there is cancer.

Imaging Tests

The following imaging tests can help visualize the tumor and any obstruction in the biliary flow:

• Abdominal ultrasound: This uses high-frequency sound waves to generate images.
• Computed tomography (C): This composites multiple X-rays to create detailed images.
• Magnetic resonance imaging (MRI): This generates images with magnetic and radio waves.
• MRI cholangiopancreatography: This is a specialized MRI technique using contrast dyes.

Biopsy

A biopsy is the extraction of tissues for evaluation in the pathology lab. It provides the definitive diagnosis of solid tumor cancers like bile duct cancer.

The biopsy may be performed during the following procedures:

• Endoscopic ultrasound: This involves a specialized probe inserted through the mouth or rectum to examine and take tissue samples from the bile ducts.
• Laparoscopy: This minimally invasive surgery creates several small incisions in the abdomen to access a tumor.
• Endoscopic retrograde cholangiopancreatography (ERCP): This involves a flexible tube-like scope (called an endoscope) that is passed through the mouth to access the bile duct.
• Percutaneous transhepatic cholangiography (PTC): This involves the insertion of a needle through the abdomen to access a tumor in the bile duct.
  

Cancer Staging

Once bile duct cancer is diagnosed, the biopsy along with other tests can stage the cancer. Staging is used to determine how advanced the cancer is based on the TNM classification system. By determining what stage the cancer is—from stage 0 to stage 4—the healthcare provider can ensure the appropriate course of treatment.

The TNS system is based on the size and characteristics of the tumor (T), the number of local lymph nodes with cancer cells in the (N), and whether the cancer has metastasized (spread) or not (M).

There are slight variations in how intrahepatic, perihilar, and distal bile duct cancers are staged.

^{Source: American Cancer Society}

^{Source: American Cancer Society}

^{Source: American Cancer Society}

How Is Bile Duct Cancer Treated

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

With that said, bile duct cancer is sometimes caught before it has spread and can be treated with surgery and follow-up treatment to destroy all remaining cancer cells. If the tumor cannot be removed completely, treatment focuses on slowing its spread, reducing symptoms, extending survival, and improving overall quality of life.

Surgery

Unless the cancer is clearly too advanced for surgery, most people will undergo exploratory surgery to determine if surgical resection (removal) is possible.

This is usually performed with laparoscopy rather than open surgery. With laparoscopy, a probe is inserted through very small incisions in the abdomen to examine affected tissues.

If the tumor is localized or regional with no evidence of spread, resection may be considered based on the general health of the individual and how well their liver is functioning.

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

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

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 cancer until a donor liver is found.

Adjuvant Therapies

Adjuvant therapies are used after surgery to destroy remaining cancer cells and prevent their return. Common cancer treatments like chemotherapy and radiation therapy are considered adjuvant therapies.

It is unclear how effective these therapies are in preventing cancer from returning, and there is debate as to whether adjuvant chemotherapy or radiation therapy can extend survival times even for people with early-stage bile duct cancer.

Even so, healthcare providers often recommend adjuvant therapy, since there is always a chance of remaining cancer cells after surgery.

Targeted Therapy and Immunotherapy

If genetic testing reveals that you have a specific, treatable mutation of cancer, you may be eligible for targeted therapies or immunotherapies. These treatments slow cancer growth by helping your immune system target and attack cancer cells with specific mutations.

Option include:

• Targeted drugs: Like Tibsovo (ivosidenib) and Pemazyre (pemiganitib)
• Immunotherapy drugs: Like Keytruda (pembrolizumab) or Imfinzi (durvalumab) commonly used with chemotherapy

Palliative Therapy

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

• Pain medications: Including opioid drugs like fentanyl
• Palliative radiation therapy: Used to reduce the size of a tumor or unblock a bile duct
• Biliary stenting: Involving the placement of a tube, called a stent, to improve biliary flow
• Biliary bypass: A surgical procedure to redirect biliary flow
• Percutaneous tumor ablation: Used to reduce a tumor with heat or electricity
• Percutaneous ethanol injection: In which alcohol is injected into a tumor to shrink it.
  

Prognosis and Survival Rates

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 the cancer has spread and whether the tumor is inside the liver or not.

Generally speaking, people with extrahepatic bile duct cancer have better outcomes because the liver is less likely to be affected. The outcome tends to be poor any time cancer spreads to the liver.

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.

Summary

Bile duct cancer is a rare, aggressive form of cancer that is rarely diagnosed in its early stages. Late-stage symptoms depend on where the tumor is located and often mimic hepatitis. Though several tests will be done to help diagnose suspected bile duct cancer, a biopsy is ultimately needed to confirm and stage it.

Bile cancer can be treated with surgery in some cases. In addition, treatments (chemo, radiation) are often used to prevent recurrence. When surgery is not an option, treatments are given to slow progression and improve quality of life.

Even with these efforts, survival five years after diagnosis ranges from 2% to 30%, depending on the type of bile duct cancer and how far it has spread.