All About Cholangiocarcinoma (Bile Duct Cancer)

Cholangiocarcinoma or bile duct cancer is a rare, aggressive group of tumours that can originate anywhere in the bile ducts. 

Bile ducts are a network of tubes that connect the liver and gallbladder to the small intestine. The main role of the bile duct is to carry bile (a fluid produced by the liver) into the small bowel, where it helps digest fats in food. 

What are the parts of the bile duct system?

Different parts of the bile duct system have different names. In the liver, it begins as many tiny tubes where bile collects from the liver cells. The tiny tubes come together to form tubes called small ducts, and these merge to form left and right hepatic ducts, which join together to form a common hepatic duct outside the liver. 

Another bile duct comes from the gallbladder. This is called the cystic duct. The common hepatic duct and cystic duct join together to form the common bile duct. The common bile duct passes through part of the pancreas and joins the pancreatic duct. 

The combined ducts open into the small bowel, where bile is released.

Are there different types of cholangiocarcinoma?

Depending on where the cancer occurs in the bile ducts, the following are the common types of cholangiocarcinoma:

• Intrahepatic cholangiocarcinoma: This type of cancer begins in the parts of the bile ducts within the liver. 
• Hilar cholangiocarcinoma or Perihilar bile duct cancer: This type of cancer begins in the hilum region (a region where right and left hepatic ducts leave the liver and join together to form a common hepatic duct). These are also called Klatskin tumors. Hilar cholangiocarcinoma and distal bile duct cancers are together referred to as extrahepatic bile duct cancers. 
• Distal bile duct cancer: This type of cancer occurs in the portion of the bile duct nearest the small intestine.

Who is more likely to get this type of cancer? 

The exact cause of bile duct cancer is unknown. 

People with the following factors may have a higher risk of developing bile duct cancer:

• Older age
• Obesity
• Alcohol consumption
• Smoking
• Certain conditions of the liver or bile ducts may result in an increased risk of developing cancer. For example, conditions like primary sclerosing cholangitis, bile duct stones, chronic liver disease, liver fluke infections, choledochal cyst etc. 

What are the symptoms of cholangiocarcinoma?

Bile duct cancer is asymptomatic unless the bile duct is blocked. 

Depending on the type of bile duct cancer, the following can be some of the symptoms:

• Jaundice
• Itching of skin
• Light-coloured, bulky, or greasy stools
• Dark urine
• Abdominal pain
• Loss of appetite
• Unintended weight loss

These symptoms can also occur due to other, non-cancerous reasons. You will need to  consult a doctor to know the exact reason for your symptoms.

How is this type of cancer diagnosed?

The doctor does a physical examination to look for signs of  bile duct cancer. If bile duct cancer is suspected, the exam will focus mostly on the abdomen, to check for any lumps, or fluid build up in the abdomen (called as ascites). 

The skin and the white part of the eyes (sclera) will be checked for jaundice. 

If symptoms and the results of the physical examination suggest the possibility of bile duct cancer, then the doctor will advise tests to confirm it.  These could include blood tests, scans, and other procedures.

You might be asked to go for these tests:

• Liver function test

Blood tests are done to find out the level of bilirubin in your blood. Bilirubin is the chemical that causes jaundice. Problems in the bile ducts, or liver can raise the blood level of bilirubin causing jaundice. 

The doctor may also advise tests for albumin, liver enzymes (alkaline phosphatase, AST, ALT, and GGT), and certain other substances in your blood. These tests are commonly called as a liver function test.  

If levels of these substances are higher, it might point to blockage of the bile duct. However, it doesn’t confirm if it is due to cancer or some other reason. 

• Tumour marker tests

People with bile duct cancer may have high blood levels of the tumour markers called CEA and CA 19-9.  A high level of these substances may indicate bile duct cancer. But, in some cases, it may indicate some other cancer or any other bile duct condition. 

Also, not all bile duct cancers make these tumor markers. A normal level does not mean cancer is not present.

Your doctor may recommend these scans:

• Abdominal ultrasound

This is often the first scan done in people who have symptoms such as jaundice or pain in the right upper part of their abdomen. 

• CT (Computed tomography) scan

A CT scan  may help  diagnose bile duct cancer by showing tumors in the area and also help with the staging of the bile duct tumours. 

• Magnetic resonance cholangiopancreatography (MRCP)

It is a special type of MRI and a non-invasive alternative to ERCP, which does not involve the use of an endoscope or an IV contrast agent, and is performed to obtain the detailed image of the bile duct. 

• Endoscopic retrograde cholangiopancreatography (ERCP)

ERCP is an important diagnostic procedure for cholangiocarcinoma, and involves endoscopic evaluation of the bile duct system. A doctor passes a long, flexible tube (endoscope) down your throat, through your stomach, and into the first part of the small intestine.

 A contrast dye is usually used to improve the visualization of the anatomical structures involved. The procedure can be used to obtain biopsy samples.  In some patients, where a blockage in the bile ducts is found, a stent may be placed during ERCP, to relieve the obstruction. 

• Biopsy

In this procedure, a sample of tissue is collected and examined in the laboratory to determine any abnormalities. A biopsy can be performed during ERCP if any suspicious lesion is found. 

But a biopsy isn’t always done before surgery for a possible bile duct cancer. If scans show a tumor in the bile duct, the doctor may decide to proceed directly to surgery and to treat the tumor as bile duct cancer.

What does stage mean?

Bile duct cancers can be classified in two ways, based on the purpose:

1.  To describe the extent of spread, bile duct cancers can be classified using the TNM staging. 
2.  For treatment purposes, doctors often use a simpler system based on whether or not the cancer can probably be removed (resected) with surgery.

The TNM classification used to stage cancers into stages I to IV is a complex staging for bile duct cancer. 

Here, we will classify the cancer in a simpler way by classifying each cancer into 1 of these categories. The medical team will plan the best treatment strategy based on these stages.

• Local: This type of bile duct cancer is located only within the bile duct and can be removed surgically. 
• Locally advanced: This type is located only in the area around the bile duct, but it does affect nearby organs, arteries, or veins. 
• Metastatic: The cancer has spread to reach distant parts of the body. 
• Recurrent: The cancer that has come back after treatment. 

Based on whether or not the cancer can be removed (resected) with surgery, it is termed as

• Resectable (localized) bile duct cancer: They can be completely removed through surgery. 
• Unresectable bile duct cancers: These cancers have spread too far and cannot be removed completely through surgery. Most stage III and stage IV cancers are categorized as unresectable bile duct cancers. 

How is cholangiocarcinoma treated?

Depending on the type, stage, and overall health of the patient the following are the treatment modalities for bile duct cancer:

Surgery

The following are the common surgical procedures for resectable cancers, depending on where the cancer is located:

• Intrahepatic bile duct cancers

To treat these cancers, a part of the liver containing the cancer is removed. Removing part of the liver is called a partial hepatectomy. Sometimes this means that a whole lobe (right or left part) of the liver must be removed. This is called hepatic lobectomy 

• Perihilar bile duct cancer

 Surgery for these cancers is complicated, and usually part of the liver is removed, along with the bile duct, gallbladder, nearby lymph nodes, and sometimes part of the pancreas and the small intestine. Then, the surgeon connects the remaining ducts to the small intestine. 

• Distal bile duct cancers

 Along with the bile duct and nearby lymph nodes, the surgeon removes part of the pancreas and the small intestine. This operation is called a Whipple procedure. 

Like the other operations, this is a complex procedure that requires an experienced surgeon.

Palliative surgery for bile duct cancers

When the cancer cannot be removed with surgery, certain surgical procedures may be considered to relieve cancer-related symptoms, such as jaundice, caused by blockage of the bile duct. 

These procedures do not treat cancer, but improve the patient’s quality of life.

• Stent placement

 Stent is  a small metal or plastic tube that’s put in the blocked duct. This is done to keep the duct open, to allow bile to drain into the small intestine. 

A stent is usually placed as part of either ERCP or PTC ( Percutaneous transhepatic cholangiography) procedure. Most commonly it is done during ERCP. 

• Biliary bypass

A bypass is done to relieve the obstruction, thereby reducing symptoms such as jaundice or itching. 

This is done by creating a bypass around the tumor blocking the bile duct by connecting part of the bile duct before the blockage with a part of the small intestine.

• Radiation therapy

Radiation therapy involves the usage of high-energy radiation beams to destroy cancer cells. In bile duct cancer, radiation therapy is used

• Before surgery, to shrink the cancer cells
• After surgery, to destroy the remaining cancer cells
• As the main treatment modality for cancers that haven’t spread, and where surgery is not an option.
• In advanced, cancers to relieve symptoms

Chemotherapy

Chemotherapy can be given orally or through an intravenous route. 

This therapy is given:

• Before surgery, to shrink the tumour
• After surgery, mostly along with radiation therapy, to kill the remaining cancer cells
• As the main treatment modality for cancers that have spread, to control the disease.

The following are the common chemotherapy drugs that can be given alone or in combination to treat bile duct cancer:5-fluorouracil (5-FU), Gemcitabine, Cisplatin, Capecitabine and Oxaliplatin. 

Targeted therapy

It uses specific drugs to target specific genes or proteins of cancer cells that contribute to their growth. This therapy is recommended in the advanced stages, when surgery is not an option. For example- Pemigatinib, an FGFRs (fibroblast growth factor receptors) inhibitor is used to treat bile duct cancer. 

Immunotherapy

Immunotherapy involves the usage of certain medicines to boost a person’s immune system to identify and destroy cancer cells. 

Pembrolizumab (Keytruda) and nivolumab (Opdivo) are 2 immunotherapy drugs approved for microsatellite instability-high (MSI-H) bile duct cancer.

Can cholangiocarcinoma be cured? 

Survival depends on many factors like the stage of cancer, the treatment options and the level of fitness.

Life expectancy for bile duct cancer is often expressed in five-year survival rates, which indicates what percent of people live at least 5 years after the cancer is found. 

Intrahepatic cholangiocarcinoma five-year survival rates:

• Local: 24% (24 out of 100 people survive their cancer for 5 years or more after diagnosis)
• Locally advanced: 7% (7 out of 100 people survive their cancer for 5 years or more after diagnosis. 
• Metastatic: 2% (2 out of 100 people survive their cancer for 5 years or more after diagnosis. 

Extrahepatic cholangiocarcinoma five-year survival rates:

• Local: 15% (15 out of 100 people survive their cancer for 5 years or more after diagnosis)
• Locally advanced: 16% (16 out of 100 people survive their cancer for 5 years or more after diagnosis. 
• Metastatic: 2% (2 out of 100 people survive their cancer for 5 years or more after diagnosis.