Cholangiocarcinoma is characterized by its very slow growth. For this reason, symptoms often appear only in the later stages of the disease, which is one reason why diagnosis frequently occurs too late.
Also known as cholangiocarcinomas or biliary carcinomas, these tumors are classified as adenocarcinomas, meaning they originate from the glandular tissue of the bile ducts. Bile duct carcinomas are categorized based on their anatomical location into extrahepatic, intrahepatic, and perihilar cholangiocarcinomas. Gallbladder carcinoma is also included in this group.
The most common form, accounting for 60 to 70 percent of cases, is the perihilar carcinoma, also known as the Klatskin tumor. This tumor is located where the left and right hepatic ducts join. Intrahepatic tumors are found within the bile ducts of the liver, while extrahepatic carcinomas are located outside the liver. Distal tumors occur in the final segment of the bile duct, just before it enters the duodenum.
As with many types of cancer, the exact causes of bile duct carcinoma remain unknown. Many tumors develop spontaneously. However, there are known risk factors that may increase the likelihood of developing this type of cancer. One significant risk factor is primary sclerosing cholangitis (PSC), a chronic inflammation of the bile ducts often associated with inflammatory bowel diseases like ulcerative colitis.
People with PSC have up to a 15 percent risk of developing cholangiocarcinoma. The mechanism behind this correlation is not fully understood but is believed to be related to ongoing inflammation.
Various parasitic infections of the liver and bile ducts also increase the risk of tissue transformation in the bile ducts. However, this risk factor is largely negligible in Western countries, as the parasites are mainly found in countries like Thailand, Laos, Malaysia, Japan, and Korea.
The following conditions may increase the risk of bile duct cancer:
A potential link between gallstones and cholangiocarcinoma has been suggested, but no definitive scientific evidence has yet confirmed this correlation.
Patients with bile duct carcinoma often experience no symptoms for a long time. Symptoms typically appear in more advanced stages, such as yellowing of the skin (jaundice), caused by increased levels of bilirubin in the blood. Bilirubin is a breakdown product of hemoglobin (the red blood pigment).
Normally, bilirubin is carried with bile into the intestines and excreted in the stool. In advanced cholangiocarcinoma, the tumor may block the bile ducts, disrupting bile flow and causing bilirubin to enter the bloodstream. As a result, less bilirubin reaches the intestines.
Because bilirubin normally gives stool its brown color, pale or clay-colored stools are a common symptom. Increased bilirubin excretion through the kidneys leads to dark or tea-colored urine. Other typical symptoms of bile duct carcinoma include:
- Upper abdominal pain
- Generalized itching
- Nausea
- Vomiting
- Loss of appetite
- Weight loss
The prognosis of bile duct carcinoma largely depends on whether the tumor can be completely removed surgically. If complete resection is not possible, the disease is considered incurable (palliative), and life expectancy is limited. Tumors that can be fully removed surgically have a significantly better prognosis.
During surgery, the bile ducts, gallbladder, and parts of the liver may need to be removed. These procedures typically involve major liver resections. To ensure continued bile drainage from the liver into the intestines, the surgeon may need to create new connections.
The benefit of a so-called neoadjuvant therapy (chemotherapy or radiation therapy before surgery) is not yet proven. Postoperative chemo- or radiotherapy may be considered if the tumor could not be completely removed and/or to reduce the risk of recurrence. However, there are currently no official recommendations outside of clinical studies.
In many cases, bile duct carcinoma is unfortunately inoperable. In such cases, a palliative immunochemotherapy is typically used to improve quality of life and extend survival.
Significant progress has been made in recent years. Today, first-line treatment often combines chemotherapy with immunotherapy.
For all patients with palliative-stage CCC, genetic testing of the tumor tissue is essential. CCC shows genetic mutations more frequently than many other cancers, and these can be specifically targeted in second-line therapy. Currently, approved drugs exist for FGFR2 fusions/rearrangements and IDH-1 mutations. Many additional treatment options are available and should be discussed individually with the patient.
To ensure proper bile drainage, patients may receive a stent (a plastic or metal tube) placed into the bile duct. This keeps the ducts open to allow better bile flow. In some cases, external drainage using a catheter (PTCD) may be necessary.
Overall, the prognosis for cholangiocarcinoma is generally poor. For most patients, only palliative treatment is possible. Five years after diagnosis, only 10 to 20 percent of patients are still alive.
