Bile Duct Carcinoma (Bile Duct Cancer / Cholangiocellular Carcinoma) - Information & Specialists

A characteristic feature of cholangiocarcinoma is that the tumor grows very slowly. For this reason, it is usually not detected in the early stages, and in many cases, the first signs do not appear until the disease has progressed. This is one reason why the disease is often diagnosed too late.

These tumors, also known as cholangiocarcinomas or biliary carcinomas, belong to the class of adenocarcinomas. This means that the malignant changes originate in the glandular tissue of the bile ducts. Bile duct carcinomas are classified according to their anatomical location into extrahepatic, intrahepatic, and perihilar bile duct carcinomas; cholangiocarcinoma is also included in this group.

Accounting for 60 to 70 percent of cases, perihilar carcinoma—also known as Klatskin tumor—is the most common type of bile duct cancer. This tumor is located in the area of the bile duct bifurcation, where the left and right common bile ducts converge. While intrahepatic tumors are found in the bile ducts of the liver, extrahepatic carcinomas are located outside the liver. Distal tumors occur in the final segment of the bile duct, up to its opening into the duodenum.

As with many cancers, the exact causes of bile duct carcinoma are unknown; many tumors arise spontaneously. However, there are various factors that can increase the risk of bile duct cancer. One of these risk factors is primary sclerosing cholangitis (PSC). This is a chronic inflammation of the bile ducts. It often occurs in conjunction with the chronic inflammatory bowel disease ulcerative colitis.

People with primary sclerosing cholangitis have a risk of developing the disease of up to 15 percent. It is not yet fully understood why primary sclerosing cholangitis can lead to bile duct cancer. However, it is likely related to the inflammatory processes involved.

Various parasitic diseases of the liver and bile ducts also increase the risk of malignant transformation of the tissue in the bile ducts. However, this risk factor is negligible in the Western world. This is because the parasites responsible are primarily found in countries such as Thailand, Laos, Malaysia, Japan, and Korea.

The following conditions can increase the risk of bile duct cancer:

• chronic liver diseases such as hepatitis B or C,
• alcohol-related liver diseases,
• liver cirrhosis
• HIV infection, and
• hepatolithiasis and Caroli syndrome
• congenital malformations of the liver.

A link between the occurrence of gallstones and cholangiocellular carcinoma is suspected. However, this has not yet been conclusively proven scientifically.

Patients with bile duct cancer may experience no symptoms whatsoever for a long period of time. It is only in more advanced stages that symptoms such as yellowing of the skin (jaundice) appear. This yellowing is caused by an elevated concentration of bilirubin in the blood. Bilirubin is a breakdown product of hemoglobin (the red blood pigment).

Normally, bilirubin is transported into the intestines with bile and excreted in the stool. In advanced bile duct carcinoma, however, the tumor can block the bile duct. This disrupts the flow of bile and causes bilirubin to enter the bloodstream. As a result, less bilirubin reaches the intestines.

Since this substance normally gives stool its brownish color, the stool becomes discolored. Increased excretion through the kidneys results in brownish urine. Other typical signs of bile duct cancer include:

• Pain in the upper abdomen
• Itching all over the body
• Nausea
• Vomiting
• Loss of appetite
• Weight loss

The prognosis for bile duct cancer depends on whether the tumor can be completely removed during surgery. If complete surgical removal is not possible, bile duct cancer is considered an incurable, palliative condition, and life expectancy is limited. Tumors that can be completely removed surgically have a significantly better prognosis.

During surgery, if necessary, not only the bile ducts but also the gallbladder and parts of the liver are removed. This typically involves major liver resections. To ensure that bile can continue to flow from the liver into the intestine, the surgeon may create new connections there if necessary.

The benefit of so-called neoadjuvant therapy has not yet been proven. In this approach, patients receive chemotherapy or radiation therapy before surgery to shrink the tumor. Subsequent chemotherapy or radiation therapy is particularly beneficial if complete tumor removal was not successful and/or to reduce the risk of recurrence. However, there are currently no recommendations for this outside of clinical trials.

Unfortunately, in many cases, bile duct carcinoma is inoperable. In such cases, palliative immunochemotherapy is typically administered. This is intended to improve patients’ quality of life and prolong their lives.

Significant progress has been made in this area in recent years; as a result, patients now receive chemotherapy combined with immunotherapy as first-line treatment.

All patients with palliative CCC must undergo genetic testing of the tumor tissue. CCC is more likely than other tumors to exhibit genetic mutations, which can then be targeted directly in the second line of treatment. Currently, there are approved medications for FGFR2 fusions/rearrangements and IDH-1 mutations. Many other options are available and must be discussed individually with the patient.

To ensure bile flow, patients receive a so-called stent (a plastic or metal tube) as needed. This is inserted into the bile duct. The stent keeps the bile ducts open, allowing bile to drain more easily. External drainage via the insertion of a drain is also possible (PTCD).

Overall, the prognosis for cholangiocellular carcinoma is rather poor. For a large proportion of patients, only palliative therapy is possible. Five years after diagnosis, only 10 to 20 percent of those affected are still alive.