Definition

Cholangiocarcinoma is a type of cancer that originates in the bile ducts, the passages connecting the liver, gallbladder, pancreas, and small intestine. These ducts play a crucial role in allowing the flow of bile. Cholangiocarcinoma is the second most common liver malignancy globally, following hepatocellular cancer. The disease occurs in 1 to 6 people per 100,000 worldwide.

Causes

Cholangiocarcinoma occurs when cells in the bile duct mutate or undergo genetic changes. These alterations lead to uncontrolled cell growth, forming masses that can invade healthy tissues. Usually, cholangiocarcinoma develops without a specific trigger or identifiable risk factors. However, some instances are associated with prolonged bile duct inflammation (cholangitis) and parasitic infections. Both conditions damage healthy cells, prompting the body to stimulate the production of new bile duct cells rapidly. The cells are forced to replicate quickly to replace the damaged ones, and at some point, faulty replication occurs, causing changes in the genetic sequence and altering cell function.

These cancerous cells typically grow slowly and initially attack the lining of the bile duct. Subsequently, they may spread to the liver, the portal vein in the liver, and the lymph nodes around it. In more severe cases, cancer cells may be found in other body parts, such as the lungs, spreading through the bloodstream or lymphatic system.

Risk Factors

Some risk factors related to the bile duct can increase the risk of cholangiocarcinoma:

• Cholangitis: Inflammation of the bile duct, especially primary sclerosing cholangitis (PSC), can lead to inflammation followed by hardening and changes in tissue, resulting in scar tissue.
• Chronic Liver Diseases: Conditions such as hepatitis and fatty liver, whether due to alcohol consumption or other causes, can lead to scarring on the liver, increasing the likelihood of cholangiocarcinoma.
• Parasite Infections: Infections from parasites, particularly worms, can heighten the risk, especially after consuming raw or uncooked fish.

In addition to the mentioned factors, other risk factors increase the likelihood of cholangiocarcinoma. Hereditary bile duct disorders, such as bile duct cysts, inherited within families, can contribute to an increased risk of cholangiocarcinoma. Genetic disorders like cystic fibrosis and Lynch syndrome, which are inherited conditions, can also elevate the risk. Age is another factor, with the disease appearing more frequently in individuals older than 50. Smoking habit is identified as a risk factor, and individuals with diabetes mellitus type 1 or 2 also face an increased risk of developing cholangiocarcinoma.

Symptoms

The symptoms and signs of cholangiocarcinoma include:

• Jaundice or yellowish eyes and skin
• Pale stools
• Tea-colored urine
• Skin itchiness
• Unintended drastic weight loss
• Abdominal pain

Jaundice, characterized by yellowing of the eyes and skin, is the most common symptom and can occur in early and advanced stages. Itchiness often accompanies jaundice, particularly if bile spreads throughout the body. Weight loss may or may not be present. Abdominal pain, described as a dull ache in the upper right abdomen, is typically more prominent in advanced stages.

Diagnosis

A direct examination is conducted to diagnose cholangiocarcinoma and identify the signs and symptoms mentioned above, including detecting enlarged lymph nodes in the abdomen. Laboratory tests include liver enzyme examination, alkaline phosphatase (ALP), and bilirubin examination. These findings help doctors predict the location of cancer, whether it is extrahepatic or intrahepatic. Additionally, tumor markers like CA 19-9, carcinoembryonic antigen (CEA), and alpha-fetoprotein (AFP) are examined.

Imaging tests can be performed in facilities that predict the cancer's location. Ultrasonography (USG) is a relatively accessible exam to detect bile duct dilation and rule out bile stones. A CT scan is preferred in more comprehensive facilities as it can detect cancer quickly. MRI can also be conducted to examine liver tissue. A PET scan may be less commonly performed, although it is rare in Indonesia.

The gold standard for diagnosis involves obtaining cancer tissue for lab examination. This is achieved using specific tools, with the tissue extraction guided by a CT scan. This examination is crucial for determining the diagnosis before initiating the management process.

All these examinations collectively contribute to determining the stage of cancer, which is essential for deciding the appropriate treatment.

Management

The management of cholangiocarcinoma aims to reduce symptoms or cure the condition, depending on the severity and stage of the cancer. One approach to cure is surgery, but its feasibility depends on factors such as the tumour's location, involvement of the bile duct, affected lymph nodes, other organs, and the tumour's proximity to nearby blood vessels. Generally, extrahepatic tumors can be surgically treated, but there is a risk of recurrence several months or years after a successful surgery.

Surgery is not recommended in advanced stages due to increased risks. In such cases, therapy aims to alleviate symptoms and improve the patient's quality of life. For instance, patients with blocked bile ducts may benefit from stent placement to create a passage for bile flow. Procedures like connecting one bile duct to another or creating a bypass can also be employed. Liver transplantation may be considered in specific cases that meet the criteria.

Another therapeutic option is radiation therapy, often used to shrink the tumor size, making it more amenable to surgery. This therapy is typically accompanied by chemotherapy or medications aimed at killing cancer cells. Such treatments are commonly administered before surgery and involve various branches of medicine, including medical hematology-oncology, radiation oncology, and surgical oncology. Oncology refers to the branch of medicine dedicated to studying and treating cancer.

Complications

Complications can arise due to the presence of cancer, surgical procedures, and therapy, including radiotherapy or chemotherapy. Individuals may be at risk of developing colangitis, leading to bile duct obstruction. Additionally, those with cholangiocarcinoma are more susceptible to liver cirrhosis, which can result from the spread of cancer cells or inflammation of the bile duct causing scarring tissue. Following surgery, the most common complication is the recurrence of the tumor.

Prevention

To reduce the risk of cholangiocarcinoma, follow these steps:

• Quit smoking: For smokers, stopping smoking is the most effective way to reduce the risk. If attempts to quit have been unsuccessful, consult with your doctor and work together to overcome the smoking habit.
• Limit alcohol intake: Reduce or avoid alcohol consumption. The recommended limits are one portion per day for women and two portions for men.
• Maintain an ideal body weight: Maintaining an ideal body weight can contribute to the prevention of cholangiocarcinoma.
• Avoiding dangerous chemicals: If you work with hazardous chemicals, adhere to safety rules and guidelines to minimize exposure.

When to see a doctor?

If you experience prolonged fatigue, abdominal pain, yellowish skin or eyes, or other concerning signs or symptoms, it is advisable to consult with a doctor. You may be referred to a gastroenterologist, a specialist who studies the digestive tract.