Bile Duct Cancer Treatment

Introduction

Liver cancer, and more specifically bile duct cancer, has become increasingly common in the past few decades. However, the treatment of such cancers still presents a challenge. A wide range of treatment options exists that depends on the symptoms experienced, where the cancer is located, and the stage that the cancer is at, all of which the doctor will take into account when formulating a treatment plan. In this article, we aim to clarify the ins and outs of each of these treatment options.

What is bile duct cancer?

A bile duct is a tube that carries bile from one organ to another - most commonly, this network of tubes connects the liver to the small intestine and the gallbladder. This network begins in the liver, where the various ducts collect bile to break down fats during digestion. These ducts then transport the bile outside of the liver.1 According to the National Cancer Institute (NCI), bile duct cancer is a rare disease where malignant cells form in the bile ducts -  malignant refers to abnormal cells that divide without control in a specific part of the body.2 This form of cancer is also referred to as cholangiocarcinoma.

Types of bile duct cancer 

There are primarily two different types of bile duct cancer that are differentiated by looking at where the cancer first started: 

  • Intrahepatic bile duct cancer - originating inside the liver.
  • Extrahepatic bile duct cancer - the tumours are found in the ducts outside of the liver. 

There are then two types of extrahepatic bile duct cancers. 

  • Perihilar bile duct cancer - found in the area where the right and left bile ducts exit the liver and form the common hepatic duct.
  • Distal bile duct cancer - found in the area where the ducts from the liver and gallbladder join to form the common bile duct.1,3 

Symptoms

Bile duct cancer rarely shows many symptoms until the condition has progressed to later stages of the disease - most commonly when the bile duct itself is fully or partially blocked. 

However, the most common clinical symptom is jaundice, where your skin and the whites of your eyes display a yellow hue. This occurs when the bile that the liver has created cannot be gotten rid of.6 This bile contains a chemical called bilirubin which is of yellowish colouring and which, instead of travelling to the intestine, gets absorbed into the bloodstream before settling in different parts of the body, causing the skin to look yellow. This buildup of bilirubin can often cause the skin to itch, which is a common symptom in bile duct cancer patients. This buildup of the chemical can also cause dark urine. Furthermore, a consequence of bilirubin not reaching the intestine is lighter-coloured or greasy stools.

Other common symptoms of bile duct cancer are a loss of appetite often accompanied by unintentional weight loss. Fatigue, lethargy, as well as stomach cramps, are also commonly reported. Less common symptoms of bile duct cancer can also be a high temperature and shivers, often accompanied by nausea and vomiting.6 

However, It is important to remember that bile duct cancer symptoms can be hard to notice and sometimes, no symptoms will manifest at all. The earlier that bile duct cancer is diagnosed by identifying these symptoms, the better the treatment is likely to work. 

Risk factors

Not everyone is at an equal risk of developing bile duct cancer. Risk factors are things that increase an individual’s chance of developing a disease. According to the American Cancer Society, in the case of bile duct cancer, the main risk factor is having a pre-existing condition affecting the liver or bile duct, for example, conditions such as primary sclerosing cholangitis, a progressive disease where the bile ducts become blocked by inflammation. More generally, other risk factors may include having inflammatory bowel disease, older age, obesity, family history, diabetes, and an elevated alcohol consumption.  

Diagnosis

The choice of diagnostic method depends on the doctor. Bile duct cancer can be diagnosed in several different ways. If bile duct cancer  is suspected, your doctor may suggest one of the following ways to help diagnose it:

  • A liver function test, i.e. a blood test measuring your liver function, which will give your doctor insight into what may be causing your symptoms. 
  • Various imaging tests allow doctors to see internal organs and look for signs and markers of specific cancers. The imaging techniques that are often used to diagnose bile duct cancer include CT scans and MRI scans. These are often done in conjunction with magnetic resonance cholangiopancreatography (MRCP), which allows for 3D images to be produced, making a series of more detailed images of the areas of interest such as the liver, the bile ducts, gallbladder and more. 
  • A biopsy, whereby a sample of tissue is removed for testing. 
  • An endoscopic retrograde cholangiopancreatography (ERCP), where a thin tube with a camera is passed down the throat to the small intestine to examine the bile duct. This technique is also often used to inject dye into the bile ducts to enhance the quality of the imaging tests that are performed or even to acquire a sample for a biopsy.2

Once a diagnosis of bile duct cancer is given, your doctor will then determine what stage your cancer is at and whether it has spread to any surrounding areas, such as surrounding lymph nodes. This is achieved by performing additional tests. Determining what stage the cancer is at is important as it will influence your doctor’s decision in regards to your treatment plans and your prognosis.

Treatments

Surgery

There are generally two types of surgery that can be performed for biliary tract cancer: 

  • potentially curative surgery
  • palliative surgery 

Most doctors agree that surgery is one of the only real chances of completely curing people with bile duct cancer. In certain cases of bile duct cancer, it may be possible to remove the cancer with surgery (resectable cancer). This is often the case for intrahepatic bile duct cancer, where the cancer is in the bile ducts that are inside the liver. The surgery in question is performed to remove the part of the liver containing the cancer. This partial removal of the liver is called a partial hepatectomy.7 

Surgery to remove bile duct cancer

Another form of surgery often performed in the case of bile duct cancer is the removal of the bile duct. This is often performed in the case of extrahepatic bile duct cancer, where the cancer is in the bile ducts that are outside the liver. The surgeon will remove the bile ducts containing the cancer. This is often only done if the tumour is small and in one bile duct only. In this case, surrounding lymph nodes are also removed, and tissue around the lymph nodes is often checked to see if there is any cancer as well. 

Surgery to control symptoms of bile duct cancer

Surgery can also be performed to control the symptoms of bile duct cancer. For example, surgery can be performed to unblock the bile duct or stop it from getting blocked. Both of these forms of palliative surgery can alleviate some of the symptoms that are associated with bile duct cancer, such as jaundice and nausea, which are often caused by the bile created by the liver being unable to make its way to the small intestine. 

In all cases requiring surgery, there is a risk of side effects associated with surgery, such as blood clots, bile leakage into the abdomen, infections or even liver failure. However, your surgeon will go over these with you. 

Chemotherapy

Chemotherapy is a form of treatment that we often associate with cancer. However, in the case of bile duct cancer, chemotherapy does not cure it but helps ensure a better quality of life and a better life expectancy. More specifically, the chemotherapy will help slow the tumour’s growth and inevitably shrink it. It is for these reasons that chemotherapy is often given to patients after surgery to get rid of any remaining cancer cells left behind.3 

Chemotherapy is often accompanied by a wide range of side effects that can greatly impact the patient, such as tiredness, nausea and vomiting, hair loss, and anaemia, among others. 

Radiotherapy

Similarly, radiotherapy is often used when treating cancer but is not a common treatment for bile duct cancer. Your doctor will often suggest radiotherapy as an option if you are unable to undergo surgery or in an effort to help control the symptoms being experienced as a form of palliative treatment. 

Liver transplant (being tested in clinical trials)

In certain cases, a liver transplant may be proposed as a treatment option for patients with bile duct cancer. In a liver transplant, the whole liver is removed and replaced with a new liver. However, this is currently only being tested in clinical trials, and often other treatments are administered while the patient awaits a donated liver.5 

Liver transplants come with a host of potential side effects, mostly those associated with any transplant surgery, such as rejection of the donated liver, infections, blood clots and particular bile duct complications such as bile duct leaks. 

Targeted Therapy (being tested in clinical trials)

Targeted therapy for bile duct cancer is also currently being tested in clinical trials. Targeted therapy is a new way of treating cancer that identifies and targets specific proteins that control how cancer cells multiply and spread. More specifically, it works by interfering with specific proteins that help the tumours grow and spread. It is either administered via small pills that you can swallow or interveinal through a needle in a blood vein. 

Although targeted therapy was first believed to cause fewer side effects than chemotherapy, there are side effects that are associated with this form of treatment that make it less optimal for certain patients. Targeted therapy is often associated with the manifestation of side effects like diarrhoea and liver problems. Other side effects can include problems with blood clotting, high blood pressure, and fatigue. 

Immunotherapy (being tested in clinical trials)

In general, your immune system helps your body fight diseases and infections - it destroys foreign and abnormal cells that it detects in the body. Immunotherapy is an emerging form of biological therapy designed to treat certain types of cancer. It works by helping the patient’s immune system combat the cancer by administering substances that boost or restore the body’s natural defences against cancer.8 

Some of the common side effects associated with immunotherapy include particular skin reactions such as pain, swelling, redness, itchiness, and certain flu-like symptoms that are not limited to fever, chills, and nausea. Other more general side effects include heart palpitations, diarrhoea and organ inflammation. These side effects occur when the immune system, which is boosted to act against cancer cells, also acts against healthy cells. 

Follow up after treatment for bile duct cancer

If you have received treatment for bile duct cancer, it is common to have regular follow-up appointments. This is the case regardless of whether the treatment completely or partially cured the cancer. The follow-up appointments tend to be every three months for the first couple of years and then every six months for the next few years. Your doctor will discuss with you the best course of action for you to make sure that your progress is regularly monitored.

Living with terminal cancer

Living with terminal cancer is something that everyone comes to terms with in their own time. You may experience a range of emotions from fear, shock, anger and denial to sadness and frustration - it is not something which is linear. You may also feel alone even if you have family and friends around you. It is important to discuss your diagnosis thoroughly with your doctor and to inquire about what support is available to you. Depending on where you live, there are various associations and charities, such as Macmillan Cancer Support, that exist to help you along the way, each of which offers various support groups, counselling, information services about your illness, and much more. 

Summary

In summary, bile duct cancer is a form of cancer where tumours are found in the biliary tract. Where the cancer is, the stage of the cancer, whether it is only affecting the bile ducts or if it has spread to the liver, lymph nodes or other places, whether the cancer can be completely removed by surgery, or whether the patient has other conditions, will all affect bile duct cancer prognosis (i.e. your chance of recovery) and will have a further effect on treatment options. If you are diagnosed with bile duct cancer, it is important to discuss treatment options thoroughly with your doctor.

References 

  1. Marcano-Bonilla L, Mohamed E, Mounajjed T, Roberts L. Biliary tract cancers: epidemiology, molecular pathogenesis and genetic risk associations. Chinese Clinical Oncology. 2016;5(5):61-61.
  2. Banales J, Cardinale V, Carpino G, Marzioni M, Andersen J, Invernizzi P et al. Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA). Nature Reviews Gastroenterology & Hepatology. 2016;13(5):261-280.
  3. Sasaki T, Takeda T, Okamoto T, Ozaka M, Sasahira N. Chemotherapy for Biliary Tract Cancer in 2021. Journal of Clinical Medicine. 2021;10(14):3108.
  4. Khan S, Davidson B, Goldin R, Heaton N, Karani J, Pereira S et al. Guidelines for the diagnosis and treatment of cholangiocarcinoma: an update. Gut. 2012;61(12):1657-1669.
  5. Safarpour A, Askari H, Ejtehadi F, Azarnezhad A, Raeis-Abdollahi E, Tajbakhsh A et al. Cholangiocarcinoma and liver transplantation: What we know so far?. World Journal of Gastrointestinal Pathophysiology. 2021;12(5):84-105.
  6. Cha J. Early bile duct cancer. World Journal of Gastroenterology. 2007;13(25):3409.
  7. Seyama Y. Current surgical treatment for bile duct cancer. World Journal of Gastroenterology. 2007;13(10):1505.
  8. Waldman A, Fritz J, Lenardo M. A guide to cancer immunotherapy: from T cell basic science to clinical practice. Nature Reviews Immunology. 2020;20(11):651-668.

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