Bay Biosciences provides high quality, clinical grade tissue samples, FFPE Blocks with matched cryogenically preserved K2EDTA plasma, sera (serum) and peripheral blood mononuclear cells (PBMC) biofluid samples from cholangiocarcinoma patients.
The K2EDTA plasma, sera (serum) and PBMC biofluid specimens are processed from cholangiocarcinoma patient’s peripheral whole-blood using customized collection and processing protocols.
Cholangiocarcinoma Overview
Bile duct cancer is also called cholangiocarcinoma (CCA) that affects the bile ducts. Bile duct cancer is a rare disease in which malignant (cancer) cells form in the bile ducts. A patient’s outlook will depend on the location of the cancer and the stage of the disease when they receive a diagnosis.
The bile ducts are thin tubes that connect the liver to the small intestine. The primary role of the bile ducts is to act as a passage for bile from the liver and gallbladder into the small intestine. Bile helps in the digestion and absorption of fat in food.
Cholangiocarcinoma occurs when old and abnormal cells in the bile duct start to grow without restrictions. Bile duct cancer can occur in any part of the bile duct system.
Different types of biliary cancer are named after where the cancer forms. Intrahepatic bile duct cancer starts in the bile ducts inside the liver. Extrahepatic bile duct cancer starts in the bile ducts outside the liver. Gallbladder cancer begins in the walls of the gallbladder.
Research estimates that 3,000–30,000 patients in the United States have cholangiocarcinoma, with about 8,000 patients receiving a diagnosis of cholangiocarcinoma every year.
Structure and Function of Bile Duct
The biliary system produces a fluid called bile, which helps digest food. Bile is made in the liver and stored in the gallbladder. The bile ducts are tree-like structures within and around the liver and gallbladder. They carry bile from the liver to the upper part of the small intestine (duodenum).
Types of Cholangiocarcinoma
Cholangiocarcinoma or bile duct cancers are classified into two types depending on where they first appear:
- Intrahepatic bile duct cancer: This type of cancer forms in the bile ducts inside the liver. Only a small number of bile duct cancers are intrahepatic. Intrahepatic bile duct cancers are also called intrahepatic cholangiocarcinoma’s.
- Extrahepatic bile duct cancer: This type of cancer forms in the bile ducts outside the liver. The two types of extrahepatic bile duct cancer are perihilar bile duct cancer and distal bile duct cancer:
- Perihilar bile duct cancer: This type of cancer is found in the area where the right and left bile ducts exit the liver and join to form the common hepatic duct. Perihilar bile duct cancer is also called a Klatskin tumor or perihilar cholangiocarcinoma.
- Distal bile duct cancer: This type of cancer is found in the area where the ducts from the liver and gallbladder join to form the common bile duct. The common bile duct passes through the pancreas and ends in the small intestine. Distal bile duct cancer is also called extrahepatic cholangiocarcinoma.
- Gallbladder cancer: A cancer that arises in the wall of the gallbladder. Gallbladder cancer is often found when looking for or during surgery to remove gallstones.
Patients may refer to perihilar and distal bile duct cancers as extrahepatic bile duct cancer, as they start outside the liver. Cancers that start in different parts of the bile ducts can cause different symptoms.
Signs and Symptoms of Cholangiocarcinoma
According to the American Cancer Society (ACS) notes that bile duct cancers do not typically cause symptoms until a later stage in the disease. However, in some cases, the symptoms may become apparent sooner.
Symptoms that a person with bile duct cancer may experience include:
- Abdominal Pain
- A lack or partial loss of appetite
- Clay colored stools
- Dark colored urine
- Fever
- Fatigue
- Jaundice, yellow coloring of the skin
- Itchy skin
- Nausea and vomiting
- Unexplained Weight Loss
Although the exact cause of bile duct cancer is unknown, researchers believe that there is a link between cholangiocarcinoma and factors that irritate and inflame the bile ducts. These factors may include:
- Bile duct stones
- Parasite infestation
- Bile duct cysts
Inflammation in the bile ducts may lead to DNA changes in bile duct cells, which may cause the uncontrolled growth of these cells.
Gene mutations may also increase the likelihood of bile duct cancer occurring. Some genes that may play a role in bile duct cancers include:
- TP53
- KRAS
- HER2
- ALK
Certain factors can increase the risk of a person developing cholangiocarcinoma. Some risk factors include the following:
- A family history of cholangiocarcinoma
- Cirrhosis
- Chronic ulcerative colitis
- Chinses liver fluke parasite infection
- Diabetes
- Excessive alcohol consumption
- Having a high body mass index (BMI)
- Infection with the hepatitis B or hepatitis C virus
- Older age
- Primary sclerosing cholangitis
Additional Risk Factors
Anything that increases your chance of getting biliary cancer is a risk factor. Bile duct and gallbladder cancer risk factors include:
Age: Most cases of biliary cancer in the United States are diagnosed in people between the ages of 50 and 70.
Ethnicity: In the U.S., Native Americans are more likely to get biliary cancers.
Medical conditions: Having any of the following may increase your risk for biliary cancer:
- Primary sclerosing cholangitis (PSC): A progressive autoimmune disease which scars the bile ducts over time.
- Chronic liver diseases, including:
- Cirrhosis
- Bile duct stones
- Cholangitis
- Non-viral chronic liver disease
- Polycystic liver disease
- Hepatitis B or hepatitis C infection
- Inflammatory bowel diseases, including:
- Crohn’s disease
- Ulcerative colitis
- A history of bile duct cysts (choledochal) which are prone to chronic inflammation.
- Liver fluke infection: Liver flukes are parasites that are more common in South and Southeast Asia. Infection may arise due to the consumption of raw or undercooked fish.
- Exposure to thorotrast, a medical contrast agent that is no longer in use.
Smoking: Smoking increases the risk of many cancers, including bile duct cancer.
Excessive consumption of alcohol: Excessive consumption of alcohol likely increases the risk of biliary cancer. This is especially true for people who have alcohol-associated liver damage.
Family history: Several genetic disorders, including Lynch syndrome, may increase the risk of biliary tract cancers.
Stages of Cholangiocarcinoma
Doctors use the TNM staging system to stage bile duct cancer:
- T refers to the tumor size and any spread of cancer into nearby tissue.
- N refers to the spread of cancer to nearby lymph nodes.
- M refers to metastasis, which means the spreading of cancer to other parts of the body.
All three types of bile duct cancers have slightly different staging systems. However, all three staging systems range from 0 to 4, with stage 4 being the most advanced type of cancer.
Prevention of Cholangiocarcinoma
To reduce your risk of cholangiocarcinoma, you can:
- Stop smoking: Smoking is linked to an increased risk of cholangiocarcinoma. If you smoke, stop. If you have tried quitting in the past and haven’t been successful, talk with your doctor about strategies to help you quit.
- Reduce your risk of liver disease: Chronic liver disease is associated with an increased risk of cholangiocarcinoma. Some causes of liver disease can’t be prevented, but others can. Do what you can to take care of your liver.For instance, to reduce your risk of liver inflammation (cirrhosis), drink alcohol in moderation, if you choose to drink. For healthy adults, that means up to one drink a day for women and up to two drinks a day for men. Maintain a healthy weight. When working with chemicals, follow the safety instructions.
Causes of Cholangiocarcinoma
Doctors don’t know exactly what causes cholangiocarcinoma. The risk factors suggest that health conditions that cause chronic (long-term) inflammation in the bile ducts may play a role in the development of this cancer.
Persistent damage like inflammation can also lead to DNA changes, which may change the way certain cells grow, divide and behave. These changes probably aren’t inherited, which means parents don’t pass them to their children. Instead, the changes likely happen during a person’s lifetime.
Diagnosis of Cholangiocarcinoma
Blood Tests. Some of these diagnostic tests will tell your doctor whether your liver is working properly. Doctors will also look for signs of tumors, called markers. Your doctor may also check your levels of bilirubin, which can cause jaundice when you have a lot of it.
Endoscopy: This test uses a tool called an endoscope that’s like a camera on the end of a cable. It lets your doctor see inside your body without surgery. They can look at your esophagus, your stomach, and the beginning of your lower intestine.
Cholangioscopy. This procedure helps check your bile ducts for problems. In ERCP, or endoscopic retrograde cholangiopancreatography, your doctor uses an endoscope to inject dye into your bile ducts. They then take X-rays to look for tumors.
Magnetic resonance cholangiopancreatography (MRCP). This uses an MRI machine to make images of your bile ducts.
Percutaneous transhepatic cholangiography (PTC). Your doctor inserts a needle through your skin and into a bile duct in your liver. They inject dye and take an X-ray of the area.
Treatment of Cholangiocarcinoma
Treatments for cholangiocarcinoma (bile duct cancer) may include the following:
- Biliary drainage. Biliary drainage is a procedure to restore the flow of bile. It might involve placing a thin tube into the bile duct in order to drain the bile. Other strategies include bypass surgery to reroute the bile around the cancer and stents to hold open a bile duct being collapsed by cancer. Biliary drainage helps relieve signs and symptoms of cholangiocarcinoma.
- Chemotherapy: Chemotherapy uses drugs to kill cancer cells. Chemotherapy may be used before a liver transplant. It may also be an option for patients with advanced cholangiocarcinoma to help slow the disease and relieve signs and symptoms. Chemotherapy drugs can be infused into a vein so that they travel throughout the body. Or the drugs can be administered in a way so that they are delivered directly to the cancer cells.
- Heating cancer cells: Radiofrequency ablation uses electric current to heat and destroy cancer cells. Using an imaging test as a guide, such as ultrasound, the doctor inserts one or more thin needles into small incisions in your abdomen. When the needles reach the cancer, they’re heated with an electric current, destroying the cancer cells.
- Immunotherapy: Immunotherapy uses your immune system to fight cancer. Your body’s disease-fighting immune system may not attack your cancer because the cancer cells produce proteins that help them hide from the immune system cells. Immunotherapy works by interfering with that process. For cholangiocarcinoma, immunotherapy might be an option for advanced cancer when other treatments haven’t helped.
- Liver transplant: Surgery to remove your liver and replace it with one from a donor (liver transplant) may be an option in certain situations for patients with hilar cholangiocarcinoma. For many patients, a liver transplant can be a cure for hilar cholangiocarcinoma, but there is a risk that the cancer will recur after a liver transplant.
- Photodynamic therapy: In photodynamic therapy, a light-sensitive chemical is injected into a vein and accumulates in the fast-growing cancer cells. Laser light directed at the cancer causes a chemical reaction in the cancer cells, killing them. You’ll typically need multiple treatments. Photodynamic therapy can help relieve your signs and symptoms, and it may also slow cancer growth. Patient’s need to avoid sun exposure after treatments.
- Radiation therapy: Radiation therapy uses high-powered energy beams from sources such as X-rays and protons to kill cancer cells. Radiation therapy can involve a machine that directs radiation beams at your body (external beam radiation). Or it can involve placing radioactive material inside your body near the site of your cancer (brachytherapy).
- Surgery: When possible, surgeons try to remove as much of the cancer as they can. For very small bile duct cancers, this involves removing part of the bile duct and joining the cut ends. For more-advanced bile duct cancers, nearby liver tissue, pancreas tissue or lymph nodes may be removed as well.
- Targeted drug therapy: Targeted therapy drug treatments focus on specific abnormalities present within cancer cells. By blocking these abnormalities, targeted drug treatments can cause cancer cells to die. Your doctor may test your cancer cells to see if targeted therapy may be effective against your cholangiocarcinoma.
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