Bile duct cancer (Cholangiocarcinoma) 101: Symptoms, causes, stages & treatment

What is Bile Duct Cancer (Cholangiocarcinoma)? 

Bile duct cancer is a rare type of cancer in which cancer cells form in the bile ducts. Bile ducts are a series of tubes that go from the liver and gallbladder to the small intestine. They carry bile, a fluid that helps in fat digestion and absorption.

Bile duct cancer, or cholangiocarcinoma, is a type of cancer that starts in gland cells. Cholangiocarcinoma starts in the gland cells that line the inside of the bile ducts.

The majority of bile duct cancers are cholangiocarcinoma's, and this article will cover this specific type of cancer.

Types of Bile duct cancer

Bile duct cancer can start in any part of the bile duct system. Based on where the cancers start (see the image above), they're classified into three types:

• Intrahepatic bile duct cancers
• Perihilar/Hilar bile duct cancers
• Distal bile duct cancers

Intrahepatic cholangiocarcinoma

This type of cancer originates from the smaller bile ducts branches within the liver, called intrahepatic cholangiocarcinoma.

This type of bile duct cancer is sometimes classified as liver cancer, and is the second-most common type of primary cancer after hepatocellular carcinoma (HCC).

Treatment for this type of bile duct cancer is often the same as for liver cancer.

Perihilar/Hilar bile duct cancers

These cancers start where the left and right hepatic ducts join and exit the liver.

Also known as Klatskin tumours, they are rare but quite lethal as these cancers are usually at quite an advanced stage at the point when they are discovered.

Distal bile duct cancers

These cancers are found outside the liver further down the bile duct, closer to the small intestine.

Bile duct cancer symptoms

As with liver cancer, bile duct cancers typically don't result in symptoms until it reaches an advanced stage. However, some signs that may be an indicator of cancer include:

• Yellowing of the skin and eyes (jaundice)
• Itchy skin
• Abdominal discomfort, pain and/or bloating
• Loss of appetite and weight
• Unexplained fatigue

Cancers that start in different parts of the bile ducts may also cause different symptoms.

Perihilar and distal bile duct cancers usually become symptomatic when the cancerous tumour blocks the bile duct drainage system - resulting in symptoms like jaundice, itchy skin and tea-coloured urine, along with abdominal pain and night chills/sweats.

For patients with intrahepatic cancers, they are less likely to have jaundice. These tumours may also present themselves as liver tumours.

Bile duct cancer causes and risk factors

Similar to liver cancers, any cause of chronic inflammation or infection to the bile ducts can increase the risk of developing CCA. These include:

Congenital bile duct cysts

Abnormally dilated bile ducts are usually congenital in nature and are typically diagnosed in childhood, but may develop or be detected in adulthood.

The lining of these sacs often contains pre-cancerous cells that increase the risk of developing cancer later in life.

Parasite infestation

Liver fluke infections may occur when people eat raw or poorly cooked fish infected with these tiny parasitic worms. When a human consumes food contaminated with liver flukes, these flukes then go on to live in the bile ducts and may cause bile duct cancer.

Chronic hepatitis B and C infection

A risk factor for intrahepatic cancer, chronic hepatitis infection increases the risk of cirrhosis (scarring).

Other bile duct cancer risk factors:

Smoking: Studies suggest that intrahepatic bile duct cancer is more common among heavy smokers.

Diabetes and Obesity: These metabolic conditions appear to be an increasingly associated risk factor for intrahepatic bile duct cancer.

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Bile duct cancer stages

There are different staging systems for each of the three different bile duct cancers (dependent on their origin).

Intrahepatic bile duct cancer stages

Stage zero: In this stage, abnormal cells are found in the innermost layer of tissue lining the intrahepatic bile duct. These pre-cancerous cells have a chance of developing into cancer and spreading into nearby tissue.

Stage I: Stage I intrahepatic bile duct cancer is divided into stages IA and IB. In stage IA, cancer has formed in an intrahepatic bile duct and the tumour is 5cm or smaller, while in stage lB, the tumour is larger than 5cm.

Stage II: Either the tumour has spread through the wall of an intrahepatic bile duct and into a blood vessel, or more than one tumour has formed in the intrahepatic bile duct.

Stage III: Stage III intrahepatic bile duct cancer is divided into stages IIIA and IIIB. In stage IIIA, the tumour has spread through the outer lining of the liver. On the other hand, in stage IIIB, cancer has spread to organs or tissues near the liver, such as the stomach, liver, intestine and/or nearby lymph nodes.

Stage IV: In stage IV intrahepatic bile duct cancer, cancer has spread to other parts of the body, such as the bone, lungs, distant lymph nodes, and/or tissue lining the wall of the abdomen and most organs in the abdomen.

Perihilar bile duct cancer staging

Stage zero: In stage zero perihilar bile duct cancer, abnormal cells are found in the innermost layer of tissue lining the perihilar bile duct. These pre-cancerous cells have a chance of developing into cancer and spreading into nearby tissue.

Stage I: In stage I perihilar bile duct cancer, cancer has formed in the innermost layer of tissue lining the perihilar bile duct and has spread into the muscle layer or fibrous tissue layer of the perihilar bile duct wall.

Stage II: In stage II perihilar bile duct cancer, cancer has spread through the wall of the perihilar bile duct to nearby fatty tissue or to liver tissue.

Stage III: Stage III perihilar bile duct cancer is divided into stages IIIA, IIIB, and IIIC.

• Stage IIIA is when cancer has spread to branches on one side of the hepatic artery or the portal vein.
• Stage IIIB is when cancer has spread to one or more of the following: the main part of the portal vein or its branches on both sides; the common hepatic artery; the right hepatic duct and the left branch of the hepatic artery or of the portal vein; the left hepatic duct and the right branch of the hepatic artery or of the portal vein.
• Stage IIIC is when cancer has spread to one to three nearby lymph nodes.

Stage IV: Stage IV perihilar bile duct cancer is divided into stages IVA and IVB.

• Stage IVA is when cancer has spread to four or more nearby lymph nodes.
• Stage IVB is when the cancer has spread to other parts of the body, such as the bone, lungs, distant lymph nodes, and/or tissue lining the wall of the abdomen and most organs in the abdomen.

Distal bile duct cancer

Stage zero: In stage zero distal bile duct cancer, abnormal cells are found in the innermost layer of tissue lining the perihilar bile duct. These pre-cancerous cells have a chance of developing into cancer and spreading into nearby tissue.

Stage I: In stage I distal bile duct cancer, cancerous cells have formed and have spread less than five millimeters into the wall of the distal bile duct.

Stage II: Stage II distal bile duct cancer is divided into stages IIA and IIB.

• Stage IIA is when cancer has either spread less than five millimeters into the wall of the distal bile duct but has spread to one to three nearby lymph nodes.
• Stage IIB is when cancer has spread five millimeters or more into the wall of the distal bile duct, and may or may not have spread to one to three nearby lymph nodes.

Stage III: Stage III distal bile duct cancer is divided into stages IIIA and IIIB.

• Stage IIIA is when cancer has spread into the wall of the distal bile duct and has spread to four or more nearby lymph nodes.
• Stage IIIB is when cancer has spread to the large vessels that carry blood to the organs in the abdomen, and may or may have spread to one or more nearby lymph nodes.

Stage IV: In stage IV distal bile duct cancer is when the cancer has spread to other parts of the body, such as the bone, lungs, distant lymph nodes, and/or tissue lining the wall of the abdomen and most organs in the abdomen.

Bile duct cancer diagnosis

Early detection of cancer often increases chances of survival and may lead to better treatment options for the cancer.

However, for bile duct cancer, the bile ducts are deep inside the body, so small tumours can't be seen or felt during routine physical exams.

There are also no blood tests or other tests that can reliably detect bile duct cancers early enough to be useful as screening tests.

If your doctor suspects that you may be at high risk, or that you may have bile duct cancer, they will typically have you take a full medical history and clinical evaluation to lay out your risk factors and learn more about the symptoms you are experiencing.

If the results of the physical examination point towards a possibility of bile duct cancer, your doctor may order for tests to be done.

These diagnostic tests include:

• Blood Tests (liver function tests and tumour markers)
• Imaging (CT, MRI or PET scans) - for assessment and staging
• Endoscopy with or without ultrasound) or Cholangiography- for further evaluations and biopsy

A combination of the above may be used to diagnose bile duct cancer as well.

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Bile duct cancer treatment

There are different types of treatment for patients with bile duct cancer. Treatment plans and options may vary depending on the type, stage and location of the cancer.

Three types of standard treatment are used: Surgery, radiation therapy and chemotherapy.

For localised bile duct cancer in which the cancer is isolated in an area (such as the lower part of the bile duct or perihilar area), chances are that it can be removed completely by surgery. Most patients with bile duct cancer cannot have their cancer completely removed by surgery.

For metastatic and recurrent bile duct cancers, these cannot be removed completely by surgery.

Metastatic cancer is when the cancer has spread from the primary site to other locations in the body. For bile duct cancer, this could mean a spread of cancer to the liver, intestines, other parts of the abdomen, and even distant parts of the body.

Recurrent bile duct cancer is cancer that comes back after it has been treated. The cancer may come back in the bile ducts, liver, or gallbladder. More rarely, it comes back in distant parts of the body.

All these three treatment types come with their own side effects. Do discuss with your doctor which form of treatment will be the most suitable for you.

Here's a look into the three main types of treatment used to treat bile duct cancer:

Surgery

The following types of surgery are used to treat bile duct cancer:

Bile duct removal

This surgical procedure is used to remove part of the bile duct, if the tumour is small. Lymph node tissue may also be removed and will be examined under a microscope to determine if cancer has spread to the nodes.

Partial hepatectomy

This surgical procedure removes the part of the liver where cancer is found - this could be a section of tissue, one lobe or a larger part of the liver, depending on the spread of the cancer.

Whipple procedure

This surgical procedure removes the head of the pancreas, the gallbladder, part of the stomach, part of the small intestine, and the bile duct. It leaves enough of the pancreas for it to make digestive juices and insulin.

After the surgeon removes all the cancer that can be seen at the time of the surgery, some patients may be prescribed chemotherapy or radiation therapy post-surgery in order to kill any cancer cells left.

Radiation therapy

Radiation therapy uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing and spreading.

There are two types of radiation therapy, both of which can be used to treat bile duct cancer:

• External radiation therapy uses a machine outside the body to direct radiation toward the area of the body with cancer.
• Internal radiation therapy uses a radioactive substance sealed in needles, wires, or catheters that are inserted directly into or near the cancer.

Chemotherapy

Chemotherapy uses drugs to halt the growth of cancer cells, either by killing the cells or by preventing them from dividing.

These drugs can be taken orally or can be injected into a vein, for the drugs to enter the bloodstream and reach cancer cells throughout the body - this is called systemic chemotherapy. It is used to treat metastatic and recurrent bile duct cancer.

If the drugs are injected directly into the cerebrospinal fluid, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas - this is called regional chemotherapy.

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How to prevent bile duct cancer

Since chronic HBV and HCV may lead to cirrhosis - and hence liver cancer and/or bile duct cancer - getting vaccinated HBV can reduce one's risk of getting cancer (there's currently no vaccine against HCV).

In that same vein, protecting against HBV and HCV infection is important as well. Infection can occur through:

• Unprotected sex (use condoms!)
• Sharing unsterilized needles

If you're at high risk of contracting HBV or HCV, get tested for these infections so that treatment can be administered if needed.

Lifestyle changes

Leading a healthy lifestyle with regular exercise, a healthy diet and moderate amounts of alcohol will help lower one's risk of liver cancer.

If you have viral hepatitis, you should reduce or avoid drinking alcohol completely as excessive alcohol can lead to cirrhosis, which can lead to liver cancer.

Quitting smoking will help reduce your risk of some cancers and other diseases, liver cancer included.

Managing your weight to prevent obesity lowers your risk of fatty liver disease and diabetes, which both potentially increase your risk of liver cancer.

Bile duct cancer support group & resources

For patients and caregivers, joining a support group provides opportunities to get in touch with cancer survivors, as well as current patients and caregivers.

The National University Cancer Institute Singapore provides a range of supportive care programmes & activities, during which patients and caregivers can obtain information and skills that'll help them through the cancer recovery journey.

This article was first published in Homage.