Cholangiocarcinoma is a cancer that forms in the bile ducts, the tubes that transport digestive fluid from the liver to the small intestine. The network of ducts begins as small tubes within the liver, which merge into larger channels that exit the organ. Cholangiocarcinoma is a rare disease, with about 8,000 cases diagnosed in the United States each year, and is often diagnosed after it has already spread.
Types of Cholangiocarcinoma
Cholangiocarcinoma is classified by its location within the bile duct system. This point of origin influences the cancer’s progression, symptoms, and available treatment pathways.
Intrahepatic cholangiocarcinoma develops in the smaller bile ducts located inside the liver. These ducts are part of the initial network that collects bile directly from liver cells. Tumors in this location account for approximately 10% of all cholangiocarcinomas and their management is often similar to other primary liver cancers.
The most common form is perihilar cholangiocarcinoma, which occurs just outside the liver at the hilum. This is the junction where the right and left hepatic ducts join to form the common hepatic duct. This type is also referred to as a Klatskin tumor and represents 60% to 70% of cases.
Distal cholangiocarcinoma originates in the portion of the bile duct that is closer to the small intestine. This section of the duct, known as the common bile duct, passes through the pancreas before it connects to the first part of the small intestine. Approximately 25% of bile duct cancers develop in this distal location.
Causes and Risk Factors
While the precise cause is often unclear, conditions that create long-term inflammation of the bile ducts are a strong risk factor. This chronic inflammation can lead to DNA changes in the duct-lining cells, resulting in uncontrolled growth and tumor formation. Identified risk factors include:
- Primary sclerosing cholangitis (PSC), a disease causing inflammation and scarring of the bile ducts
- Chronic liver disease, particularly cirrhosis
- Structural abnormalities of the bile ducts, such as choledochal cysts
- Infection with liver flukes, a type of parasite common in parts of Asia
- Chronic viral infections like hepatitis B or hepatitis C
- Older age, with most diagnoses occurring in people over 65
- Obesity
- Diabetes
It is important to note that many individuals diagnosed with cholangiocarcinoma have no identifiable risk factors.
Symptoms and Diagnosis
Symptoms often appear once a tumor grows large enough to obstruct a bile duct. The most common sign is jaundice, a yellowing of the skin and eyes. Jaundice occurs when the blockage prevents bile drainage, causing bilirubin to build up in the blood.
The bile backup from the obstruction causes other symptoms, including:
- Intense itching, known as pruritus
- Pale or clay-colored stools
- Dark urine as the body tries to excrete excess bilirubin
- Abdominal pain, often in the upper right side
- Unexplained weight loss
- Fatigue
The diagnostic process typically begins with blood tests to evaluate liver function and check for tumor markers, such as CA 19-9, though these are not definitive. Imaging tests are then used to get a visual of the bile ducts, starting with an ultrasound and followed by more detailed scans like a computed tomography (CT) or magnetic resonance imaging (MRI).
A specialized MRI, magnetic resonance cholangiopancreatography (MRCP), creates detailed images of the bile ducts. A biopsy is necessary to confirm the diagnosis by examining a tissue sample under a microscope. This sample can be collected via an endoscopic retrograde cholangiopancreatography (ERCP) or a percutaneous biopsy, where a needle is guided through the skin.
Treatment Approaches
The treatment plan depends on the tumor’s location and stage, as well as the patient’s overall health. The goal is either to remove the cancer or to manage its growth and symptoms.
Surgery offers the best chance for a cure and is the primary treatment for early-stage, localized cancer. The procedure involves removing the tumor along with a margin of healthy tissue. For some perihilar cholangiocarcinomas, a liver transplant may be an option, but surgery is only possible for a minority of patients.
Chemotherapy and radiation therapy are often used when surgery is not an option or to eliminate remaining cancer cells post-surgery. Chemotherapy uses drugs to kill cancer cells systemically, while radiation targets a specific area with high-energy rays. These treatments can shrink tumors, slow their growth, or relieve symptoms.
Newer modalities include targeted therapy and immunotherapy. Targeted therapy uses drugs that focus on specific abnormalities within cancer cells to stop their growth. Immunotherapy harnesses the patient’s immune system to attack the cancer. These advanced treatments are often considered based on the tumor’s molecular profile.
For advanced cancer, palliative therapies are used to improve quality of life by relieving symptoms. A common procedure is placing a stent in a blocked bile duct to hold it open. This allows bile to drain, which alleviates jaundice and itching.