Bile Duct Cancer (Cholangiocarcinoma, Klatskin tumour)

What is Bile Duct Cancer?

Bile duct cancer, also known as cholangiocarcinoma, is a rare, and aggressive type of cancer that arises from the cells lining the bile ducts. The bile ducts are thin tubes that carry bile from the liver, and gallbladder to the small intestine. Depending on its location, bile duct cancer may be classified as intrahepatic (within the liver), perihilar (near the junction of the left, and right bile ducts) or distal (near the small intestine).

In particular, Klatskin tumours are a subtype of perihilar cholangiocarcinoma that form at the confluence of the right, and left hepatic bile ducts, which is a critical area for bile drainage. These tumours are often difficult to detect early, and can pose challenges in treatment due to their central location and proximity to vital blood vessels.

Types of Bile Duct Cancer

Bile duct cancers are classified based on their location:

• Intrahepatic Cholangiocarcinoma – occurs in the bile ducts inside the liver.
• Perihilar Cholangiocarcinoma (Klatskin Tumour) – arises at the confluence of the left, and right hepatic ducts. This is the most common type of bile duct cancer.
• Distal Cholangiocarcinoma – develops in the bile ducts closer to the small intestine, outside the liver. It can be located within the pancreas.

What are the causes of Bile Duct Cancer?

The exact cause of bile duct cancer is not always clear, but several underlying factors may contribute to its development. Each of these can damage the bile duct lining over time, leading to abnormal cell growth and cancer:

• Bile Duct Cysts (Choledochal Cysts) – these congenital cysts cause bile stagnation, and repeated inflammation, increasing the likelihood of cellular mutations.

• Bile Duct Stones – like gallstones, bile duct stones can cause repeated infections, and blockages. The inflammation from these episodes can result in cellular changes that may eventually become cancerous.

• Chronic Bile Duct Inflammation – conditions such as primary sclerosing cholangitis (PSC) cause long-term inflammation of the bile ducts. This constant irritation can damage the cells, and significantly raise the risk of bile duct cancer.

• Exposure to Chemicals – long-term exposure to certain industrial chemicals such as thorotrast, used historically in radiographic imaging, has been associated with an increased risk of bile duct cancer.

• Liver Fluke Infection – infections caused by parasitic liver flukes, which is common in some parts of Asia, can irritate the bile ducts, increasing cancer risk. Though rare in Singapore, travel or immigration history may be relevant.

• Viral Hepatitis (Hepatitis B and C) – chronic hepatitis infections cause liver inflammation, which can indirectly affect bile duct function, and increase cancer risk.

What are the symptoms of Bile Duct Cancer?

Bile duct cancer is often asymptomatic in the early stages, especially intrahepatic types. Be that as it may, symptoms typically appear as the tumour grows, and blocks bile flow. These include:

• Abdominal pain (particularly in the upper right area)
• Dark urine and pale stools
• Fatigue
• Fever or recurrent chills
• Itchy skin
• Jaundice (yellowing of the eyes and skin)
• Loss of appetite
• Unexplained weight loss

Who is at risk of Bile Duct Cancer in Singapore?

While bile duct cancer can affect anyone, certain factors can increase an individual’s risk. Some of the common risk factors are:

• Age — individuals who are 65 years, and older are at higher risk due to the cumulative effects of inflammation, and age-related tissue changes.

• Gender — men are more commonly affected by bile duct cancer than women. The reason is not entirely understood but may relate to differences in hormonal or occupational exposures.

• Family History — a family history of gastrointestinal cancers, including bile duct or pancreatic cancers, may increase risk due to shared genetic or environmental factors.

• Chronic Inflammatory Conditions — diseases such as primary sclerosing cholangitis (PSC), and chronic hepatitis cause long-term inflammation, which may lead to cancerous changes in the bile duct lining.

• Congenital Bile Duct Abnormalities — conditions like choledochal cysts result in bile pooling and irritation, significantly increasing the chance of cellular mutation.

• Liver Fluke Infection — while rare in Singapore, infection with liver flukes, particularly Opisthorchis viverrini or Clonorchis sinensis, in endemic regions is a major risk factor.

• Diabetes and Obesity — both conditions can cause metabolic dysfunction, and chronic inflammation, which contribute to an increased risk of bile duct cancers.

• Smoking and Alcohol Consumption — long-term use of tobacco or excessive alcohol can contribute to liver, and bile duct damage, increasing cancer risk.

What are the complications of Klatskin Tumours?

As Klatskin tumours are a type of bile duct cancer that arise at a critical point in the biliary system (hepatic duct bifurcation), they can lead to a number of complications, particularly if left untreated:

• Obstructive jaundice – blockage of bile flow leads to yellowing of the skin and eyes, dark urine, pale stools, and itching. This is often the first sign of the disease.

• Cholangitis – infection of the bile ducts due to stagnant bile can result in fever, abdominal pain, and potentially life-threatening sepsis.

• Liver dysfunction or failure – prolonged obstruction can lead to liver damage over time.

• Malnutrition and weight loss – poor digestion due to impaired bile flow affects nutrient absorption.

• Metastasis – in advanced stages, the cancer can spread to nearby lymph nodes, liver tissue, or distant organs.

How is Bile Duct Cancer diagnosed?

Diagnosing bile duct cancer can be complex due to its location, and the non-specific nature of early symptoms. 

Physical Examination

Dr Tan Siong San will begin with a detailed consultation, and physical examination, which includes:

• Assessing medical history, and symptoms such as jaundice, fatigue or abdominal discomfort.
• Checking for signs of liver dysfunction, including yellowing of the eyes or skin.
• Palpating the abdomen to detect tenderness, swelling or masses near the liver or gallbladder.

Imaging Tests

Comprehensive imaging is essential to visualise the bile ducts, and determine the presence, size, and spread of any tumour:

• Computed Tomography (CT) Scan – provides detailed cross-sectional images of the abdomen to assess tumour location, and spread.
• Ultrasound – a non-invasive scan used to identify blockages or abnormal structures in the bile ducts or liver.
• Magnetic Resonance Cholangiopancreatography (MRCP) – offers high-resolution images of the bile ducts, and is useful for detecting strictures, blockages or tumours.
• Endoscopic Retrograde Cholangiopancreatography (ERCP) – combines endoscopy, and X-ray imaging to examine the bile ducts. This procedure may also allow for tissue sampling, and stent placement to relieve obstruction
• PET-CT Scan – helps assess the activity of cancer cells, and identify any spread beyond the bile ducts (metastasis).

Blood Tests

Blood tests are used to assess liver function, and may provide clues to the presence of cancer:

• Liver function tests (LFTs) – elevated bilirubin, alkaline phosphatase, and transaminases may indicate bile duct obstruction or liver involvement.
• Tumour markers – CA 19-9 and carcinoembryonic antigen (CEA) levels may be elevated in bile duct cancer, although these markers are not specific.

Biopsy

If the imaging results suggest cancer, a biopsy may be necessary to confirm the diagnosis. This may be done:

• During ERCP using a small brush or forceps.
• Through image-guided fine needle aspiration (FNA) using ultrasound or CT.

What are the stages of Bile Duct Cancer?

Bile duct cancer is staged based on the extent of tumour growth, involvement of lymph nodes, and spread to other parts of the body. Staging helps doctors determine how advanced the cancer is, and guides the most appropriate treatment plan.

On the other hand, staging of Klatskin tumours takes into account three main factors:

• Local tumour extent – how far the tumour has spread along or into the bile ducts, and nearby liver tissue.
• Vascular involvement – whether the tumour has encased or invaded major blood vessels such as the portal vein or hepatic artery.
• Lymph node and distant spread – whether the cancer has reached nearby lymph nodes or spread to distant organs.

A commonly used system for Klatskin tumours is the Bismuth-Corlette classification, which focuses on the tumour’s location within the biliary tree:

How is Bile Duct Cancer treated?

Treatment for bile duct cancer, including Klatskin tumours, depends on several factors such as the cancer’s exact location, stage, spread, and the patient’s overall health.

Surgical Treatment

Surgery is often the most effective option for treating bile duct cancer when the tumour is localised, and can be completely removed. The primary aim is to achieve clear margins by excising the tumour along with any surrounding affected tissue. Surgical treatment offers the only chance of curing the disease, and is usually part of a broader treatment plan that may include chemotherapy or radiation.

• Bile Duct Resection – for cancers located in the distal bile duct, the affected segment is removed along with nearby lymph nodes to minimise recurrence risk.

• Biliary Reconstruction – after removal of affected bile ducts, reconstructive techniques are used to restore bile drainage into the small intestine.

• Liver Resection – in cases of intrahepatic cholangiocarcinoma, a partial liver resection is performed to remove the tumour along with adjacent tissue.

• Whipple Procedure (Pancreaticoduodenectomy) – this is often performed when the tumour is located near the pancreas, this complex surgery involves removing the distal bile duct, part of the pancreas, gallbladder, and a portion of the small intestine. It is often used for distal cholangiocarcinomas.

Meanwhile, Klatskin tumours, surgical treatment is more complex, and often requires advanced surgical expertise. This is due to their location near critical blood vessels, and liver structures.

• Hilar Resection with Biliary Reconstruction –the involved portion of the bile duct at the liver hilum is removed. Surgeons then reconstruct the biliary system to allow bile to flow into the digestive tract.

• Extended Liver Resection – if the tumour extends into one lobe of the liver, that portion may also be removed along with the bile duct. This is done to ensure complete excision of cancerous tissue.

• Portal Vein Resection and Reconstruction – if the tumour has invaded the nearby portal vein, this segment may be surgically resected, and reconstructed. This is sometimes necessary to achieve clear surgical margins.

• Lymph Node Dissection – surrounding lymph nodes are removed, and tested to check for cancer spread, which helps in accurate staging and planning further treatment.

Non-Surgical Treatment

For patients whose tumours are inoperable, have spread to other areas or who are not fit for surgery due to other medical conditions, non-surgical treatments are used to slow disease progression, relieve symptoms, and improve quality of life.

• Biliary Stenting – for tumours causing obstruction, especially common in Klatskin tumours, a stent may be placed via ERCP to open the blocked bile duct, and relieve symptoms like jaundice.
  
• Chemotherapy – medications such as gemcitabine, and cisplatin are commonly used to shrink tumours, and slow their growth. These may be given alone or in combination with other treatments, either before surgery (neoadjuvant) or after surgery (adjuvant) or as a primary therapy.

• Radiation Therapy – often combined with chemotherapy, radiation helps target, and destroy cancer cells in cases where surgical removal is not possible.

• Targeted Therapy and Immunotherapy – these newer approaches are based on genetic, and molecular testing of the tumour. Targeted drugs focus on specific mutations, while immunotherapy helps the immune system identify, and fight cancer cells.

• Palliative Care – when a cure is no longer possible, palliative care focuses on managing pain, nausea, fatigue, and other symptoms to maintain comfort, and quality of life.

Summary

Bile duct cancer can be a daunting diagnosis, but with early detection, and the right care, there is hope. At Tan Siong San Surgery, we are committed to walking this journey with you by offering thorough evaluations, and personalised treatment strategies tailored to your unique needs.

Our clinical team is dedicated to working towards the most optimal outcome with your health, comfort, and peace of mind as our top priorities. Contact us today for a detailed diagnosis and tailored treatment plan.