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Cholangiocarcinoma

Clinical OncologyGeneral SurgeryGastroenterology Hepatology

The Bile duct located between the gallbladder and the duodenum event has a small size, but it has the potential to develop into cancer as know as “Cholangiocarcinoma”, with the risk varying by region. Generally, the older a person is, the higher the likelihood of developing the disease. According to data from the American Cancer Society, the average age of diagnosis for intrahepatic and extrahepatic cholangiocarcinoma is 70 and 72 years, respectively.

Although cholangiocarcinoma is rare, its threat should not be underestimated. According to a document by the American scholar James E. Everhart, the one-year mortality rate for cholangiocarcinoma shows some improvement, but its long-term 5-year survival rate remains below 10%. Moreover, the overall survival period for advanced cholangiocarcinoma is generally only 12 to 14 months, making it one of the most lethal types of cancer.

Most cases of cholangiocarcinoma are either intrahepatic cholangiocarcinoma or perihilar (extrahepatic) cholangiocarcinoma. In the case of intrahepatic cholangiocarcinoma, as the name suggests, the tumour grows within the small bile ducts inside the liver. However, in the early stages, there are usually no significant or distinctive symptoms. Sometimes, patients may experience mild discomfort such as abdominal pain, nausea, loss of appetite, fatigue, and weight loss, which are common daily discomforts. Patients may not readily notice or associate these with cancer. Unfortunately, by the time apparent symptoms are detected, the cancer has often reached an incurable stage.

As for perihilar cholangiocarcinoma, it grows at the junction of the left and right hepatic ducts outside the liver. Because it can easily cause bile duct obstruction, patients typically experience symptoms such as itchy skin, jaundice (yellowing of the skin and eyes), dark urine, and pale stools. Some patients may also develop acute cholangitis, leading to fever, chills, and abdominal pain.

Factors

While cholangiocarcinoma is rare, its threat should not be underestimated. According to relevant literature, the one-year mortality rate of cholangiocarcinoma shows signs of improvement. However, its long-term five-year survival rate remains consistently below 10%. For late-stage cholangiocarcinoma patients, the overall survival period is usually only 12 to 14 months, making it one of the most deadly cancers.

The medical community has not agreed on the specific causes of these genetic mutations. Some may be induced by inflammation, while others have an unknown origin or even result from random events without having apparent external factors.

However, this does not mean that cholangiocarcinoma is entirely without clues. Indications suggest that the following factors can trigger or increase the likelihood of developing cholangiocarcinoma:

Primary Sclerosing Cholangitis	An inflammatory bile duct disease associated with ulcerative colitis, causing bile duct hardening and scarring, leading to the formation of a tumour.
Chronic Liver Diseases	Some patients with certain liver diseases may develop liver scarring, increasing the risk of cholangiocarcinoma.
Congenital Bile Duct Abnormalities	Some individuals are born with bile duct cysts, leading to abnormal dilation or twisting of the bile duct, which can elevate the risk of cholangiocarcinoma.
Liver luke Infection	This condition is relatively common in Southeast Asia, where patients primarily become infected with liver flukes by consuming undercooked fish, leading to an increased risk of cholangiocarcinoma.

In addition to the disease mentioned above factors, as mentioned earlier, age is also a critical risk factor, with cholangiocarcinoma primarily affecting older individuals. Furthermore, long-term smoking habits can also increase the likelihood of developing cholangiocarcinoma.

Suppose a doctor suspects a patient may have cholangiocarcinoma. In that case, they will first conduct preliminary and straightforward examinations, inspecting for signs of abdominal swelling or fluid accumulation, as well as assessing whether the patient is experiencing pain. They will also examine the patient's skin and the whites of their eyes to determine if jaundice is present.

Liver Function Tests	Blood samples are taken to evaluate liver function, including bilirubin levels and serum alkaline phosphatase levels. However, elevated levels of both markers only indicate bile duct obstruction and do not necessarily result from a tumour. On the contrary, some early-stage patients with intrahepatic cholangiocarcinoma may have normal liver function.
Cancer Markers	The doctor will examine two markers in the patient's blood: CA19-9 and CEA. CA19-9: This is a protein that is overproduced by cholangiocarcinoma tumours. However, using CA 19-9 levels alone for cholangiocarcinoma diagnosis has limited accuracy since conditions related to bile duct inflammation and obstruction can also elevate CA 19-9 levels. Some cholangiocarcinoma patients may maintain normal CA 19-9 levels. CEA: CEA levels in cholangiocarcinoma patients may be higher than in others, but in practice, less than half of patients with cholangiocarcinoma who undergo this test will show a positive response.
CT Scan	This is used to assess the tumour's size and the extent of its destruction of nearby liver, lymph nodes, and other abdominal organ tissues. However, if the tumour is confined to the bile ducts, it may not be easily detected by a CT scan.
MRI	This is similarly used to assess the extent of the tumour's damage to nearby tissues. The doctor may use one of the following contrast imaging techniques: ERCP: An endoscope is inserted through the patient's mouth and stomach into the duodenum to locate the junction of the bile duct and pancreatic duct. Contrast material is injected through a catheter to highlight the internal condition of the entire bile duct. MRCP: It is non-invasive and does not require contrast agents, revealing images based on the natural contrast between the biliary system and other tissues. As it doesn't involve inserting a catheter into the patient's body, it has been used as an alternative to ERCP in recent years. PTC): A fine needle is inserted through the patient's skin into the dilated intrahepatic bile duct, and contrast material is injected for X-ray imaging to identify the site of bile duct obstruction.
PET CT	This is commonly used to diagnose intrahepatic malignant tumours or extrahepatic metastases. In general, cholangiocarcinoma tumours tend to spread to the peritoneum, lymph nodes, lungs, and bones.

Staging

After the diagnosis through the above methods, if the doctor discovers that the patient has bile duct cancer, further examinations may be conducted to determine the stage of cancer accurately. Factors in determining the early or late location of cancer include the tumour's size, whether it has spread to lymph nodes, and whether it has spread to more distant body tissues, such as bones or lungs. The sub-stages for intrahepatic cholangiocarcinoma and hilar cholangiocarcinoma are as follows:

Intrahepatic Cholangiocarcinoma
Stage 0	The tumour is confined to the innermost layer of the bile duct cells and has not spread.
Stage I	IA: Tumour diameter is not more than 5 cm and has not invaded nearby blood vessels or spread to lymph nodes.
Stage I	IB: Tumour diameter is over 5 cm but has not invaded nearby blood vessels and has not spread to lymph nodes.
Stage II	II: The tumour has extended to nearby blood vessels, or multiple tumours are found, regardless of vascular invasion, but has not spread to lymph nodes.
Stage III	IIIA: The tumour has enlarged and penetrated the peritoneum, the outer layer of the abdomen, but has not spread to lymph nodes.
Stage III	IIIB: The tumour has directly grown to other areas outside the liver but has not invaded lymph nodes or has spread to lymph nodes but has not reached farther tissues.
Stage IV	Any tumour size, regardless of whether it touches the external part of the bile duct and lymph nodes, has invaded farther tissues, including bones or lungs.

Hilar Cholangiocarcinoma
Stage 0	The tumour is confined to the innermost layer of the bile duct cells and has not spread.
Stage I	The tumour has grown into the muscle or fibrous tissue layer of the bile duct wall but has not invaded lymph nodes.
Stage II	The tumour has penetrated the bile duct wall and entered the fatty or liver tissue but has not spread to lymph nodes.
Stage III	IIIA: The tumour extends to one side of the liver's primary blood vessel branches but has not touched lymph nodes or farther tissues.
	IIIB: The tumour has entered the liver's major blood vessels or branches on both sides, or cancer has invaded one side of the bile duct and the major blood vessel on the other side but has not spread to lymph nodes or farther tissues.
	IIIC: Any tumour size, regardless of whether it has grown outside the bile duct or nearby blood vessels, has spread to 1 to 3 nearby lymph nodes but has not spread to farther tissues.
Stage IV	IVA: Any tumour size, regardless of whether it has grown outside the bile duct or nearby blood vessels, has spread to 4 or more nearby lymph nodes but has not touched farther tissues.
Stage IV	Any size of the tumour, regardless of whether it has grown outside the bile duct, nearby blood vessels, or lymph nodes, has spread to farther parts of the bones, lungs, or liver.

Treatments

Once diagnosed, doctors will choose the most appropriate treatment for patients with confirmed cholangiocarcinoma. Details are as follows:

Surgical Treatment	It is the most curative and preferred treatment. If conditions such as liver function, tumour size, and location are suitable, the surgeon will remove the tumour and adjacent diseased tissues directly. However, since the symptoms of intrahepatic cholangiocarcinoma are often hidden, patients are usually diagnosed at a later stage, limiting the effectiveness of tumour removal. For hilar cholangiocarcinoma, despite significant jaundice symptoms, surgery in the vicinity of the hepatic hilum or common bile duct is challenging due to the presence of numerous blood vessels and nerves.
Chemotherapy	This method is often used for patients with advanced-stage cholangiocarcinoma, where the tumour cannot be removed surgically. Chemotherapy aims to alleviate symptoms and shrink tumours, extending the patient's life. Chemotherapy itself may cause side effects, but modern chemotherapy drugs have significantly reduced side effects compared to traditional ones.
Radiation Therapy	Radiation therapy may be employed if the tumour volume is still small but cannot be removed by surgery. High-energy radiation penetrates the body, or radioactive materials are placed near the tumour to destroy or eliminate cancer cells.
Photodynamic Therapy	A photosensitizing chemical is injected into the patient's vein, and a chemical reaction is induced to kill rapidly growing cancer cells. However, this method usually provides only soothing relief, and patients may require other treatment methods.
Biliary Drainage	This method bypasses surgery by redirecting bile to the surrounding area of the tumour or placing a stent inside the body to open up bile ducts blocked by the tumour. It is commonly used to relieve symptoms of bile duct cancer.
Liver Transplantation	It applies to hilar cholangiocarcinoma, where the donor's liver is transplanted into the patient with cholangiocarcinoma. However, this method does not eliminate cholangiocarcinoma, and there is still a chance of cancer recurrence.

FAQ

HEAL Oncology Centre

We provide a variety of treatment options for Cholangiocarcinoma, including surgery, chemotherapy, targeted therapy, immunotherapy, radiation therapy, and traditional Chinese medicine. Our multidisciplinary team of specialists will tailor the best treatment plan for each patient, providing comprehensive and holistic care to ensure you receive the best possible outcomes and support throughout your cancer treatment journey.

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