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Cholangiocarcinomas (bile duct cancer)
Cholangiocarcinomas (bile duct cancer)
Cholangiocarcinomas (Bile Duct Cancer) | SingHealth
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Cholangiocarcinomas (bile duct cancer) - What it is
Cholangiocarcinomas (CCA) is more commonly known as bile duct cancer. The liver is the largest solid organ in the body and is essential for life. It is involved in many processes of the body, such as producing bile, essential proteins and nutrients. Bile ducts within the liver join together to form one main bile duct, located just outside the liver (at the hilum), which carries bile to the small intestine. This main bile duct is called the common hepatic duct. The cystic duct joins the gallbladder to the common hepatic duct, and the combined duct is called the common bile duct.
Cholangiocarcinoma is the second most common primary cancer of the liver, after hepatocellular carcinoma (HCC). It arises from cells lining the bile ducts (cholangiocytes).
They can occur within the liver (intrahepatic) or near the liver hilum (perihilar) or beyond the liver (extrahepatic or distal). Although they are rare, these cancers are highly lethal because most are diagnosed at advanced stages. Even in early stages, post-resection their rates of recurrence remain significant.
What are the types of Cholangiocarcinomas (Bile Duct Cancer)?
CCA is categorised into three types:
Intrahepatic CCA – the cancer occurs in the bile ducts within the liver
Hilar CCA – the cancer occurs in the bile ducts just outside of the liver. It is the most common form of CCA. It is also known as perihilar CCA or "Klatskin" tumours.
Distal CCA – the cancer originates outside the liver, in the bile ducts nearest to the small intestine. It is also known as extrahepatic CCA.
Cholangiocarcinomas (bile duct cancer) - Symptoms
Extrahepatic CCAs usually become symptomatic when the tumour obstructs the bile duct drainage system. Symptoms related to biliary obstruction include:
Yellowing of skin and eye (jaundice)
Itchy skin (pruritus)
Clay-coloured stools
Tea-coloured urine
Other common symptoms include:
Abdominal pain
Weight loss
Fatigue
Fever
Intrahepatic CCAs may present differently as the tumour is in the liver. Affected patients are less likely to be jaundiced. Some patients will have mild or no symptoms, and often only develop symptoms in the advance stage.
Advanced-stage symptoms include:
Pain or discomfort in the right side of the abdomen
Abdominal distension or bloating
Poor appetite
Weight loss
Fatigue
Liver failure
Symptoms related to the site the cancer has spread to (metastasis) – for instance, ascites (fluid accumulation) in the abdomen due to spread to the internal lining of the abdomen (peritoneum), pain due to spread to the bone, or breathlessness due to spread to the lungs
Cholangiocarcinomas (bile duct cancer) - How to prevent?
There are no known ways to prevent most bile duct cancers. Many of the known risk factors for bile duct cancer, such as age, ethnicity, genetics and bile duct abnormalities are beyond our control. Nonetheless, there are some things you can do that might lower your risk such as:
Healthy weight management
Exercising regularly
Eating a healthy balanced diet
Quitting or do not start smoking
Avoiding excessive alcohol consumption
Avoiding exposure to known cancer-causing (carcinogenic) chemicals
It is also important to avoid infection with the hepatitis B and C viruses. Hepatitis B and/or C infection may increase the risk of developing CCA and it can lead to liver scarring (cirrhosis), liver failure and liver primary cancer. Currently, there is no vaccine for hepatitis C but appropriately initiated treatment may control or eliminate the virus. If you have chronic hepatitis, you should visit your doctors for regular surveillance with imaging tests, such as ultrasound.
When should you see a doctor?
Make an appointment with your doctor if you have any signs or symptoms that worry you.
Cholangiocarcinomas (bile duct cancer) - Causes and Risk Factors
Any cause of chronic inflammation and/or infection to the bile ducts can increase the risk of developing CCA due to prolonged and repeated damage. These include bile duct stones or parasites (e.g. liver flukes, recurrent pyogenic cholangitis).
These are some other inflammatory conditions that can increase the risk of developing CCA:
Ulcerative Colitis – This is chronic inflammation of the large intestine that is often associated with inflammation of the bile duct (a condition known as sclerosing cholangitis). Patients with primary sclerosing cholangitis (PSC) are at an increased risk for CCA.
Congenital Bile Duct Cysts (Choledochal Cysts) - These are abnormal dilated bile ducts; they are usually congenital in nature and are typically diagnosed in childhood but may develop or be detected in adulthood. The lining of these sacs often contains pre-cancerous cells that increase the risk of developing cancer later in life.
Parasite infestation - Liver fluke infections are not uncommon especially in Asia, it occurs when people eat raw or poorly cooked fish that are infected with these tiny parasite worms. In humans, these flukes live in the bile ducts and can cause bile duct cancer. The types most closely related to CCA are Clonorchis sinensis, Schistosomiasis japonica and Opisthorchis viverrine.
Chronic Hepatitis C infection – This is a risk factor for intrahepatic CCA.
Exposure to cancer-causing (carcinogenic) agents such as asbestos, thorotrast, dioxins, nitrosamines, and vinyl chloride has been linked to causing CCA.
Smoking – Studies suggests that intrahepatic CCA is more common among heavy smokers.
Diabetes and Obesity - These metabolic conditions are increasingly associated as risk factors for intrahepatic CCA.
What are the complications of Cholangiocarcinomas (Bile Duct Cancer)?
In some patients, CCA can lead to the formation of a tumour that blocks the bile duct, resulting in the bile drainage system (cholangitis) getting infected.
Additionally, CCA may lead to the development of cirrhosis and result in scarring and damage to the liver cells, particularly patients with primary sclerosing cholangitis.
Cholangiocarcinomas (bile duct cancer) - Diagnosis
There is a lack of effective non-surgical treatment options. It is important to get an accurate diagnosis of CCA so that your condition can be treated appropriately. Your doctor will ask questions about your medical and family history, lifestyle habits and perform a physical examination.
Ultrasound
An ultrasound uses high-frequency sound waves to scan, carries no radiation risk and can be done on a regular basis, especially in individuals who are at risk of cancer, for e.g. hepatitis C carriers. It is however not always accurate and or very specific and sometimes further CT or MRI scans may be indicated for better characterisation of the tumour.
CT scan
The CT scan is an x-ray procedure that produces detailed cross-sectional images of the body from different angles. It is a better way of detecting CCA and is crucial for treatment planning. In certain cases, a CT scan may not be enough or is inconclusive, and additional investigations like MRI / MRCP or a PET scan may be performed.
Blood test
A blood test that measures the tumour markers called Carbohydrate antigen 19–9 (CA 19-9) can indicate an association with CCA but it should not be used or as a routine screening test. Other tumour markers that are associated are carcinoembryonic antigen (CEA) and CA-125.
A blood test alone is usually not diagnostic and a further tissue sample or biopsy, i.e. a small tissue or cells sample from the bile duct may be collected through a needle procedure or via endoscopy brushing.
Other scans or investigations may be required if necessary for diagnosis, staging and/or to guide treatment strategy.
What are the stages of Cholangiocarcinomas (Bile Duct Cancer)?
Staging helps your medical team to assess the extent of the cancer in your body, plan treatment and determine your prognosis. Staging guidelines differ depending on the type of CCA. In general, CCA staging factors include:
Size of the tumour
Whether the cancer has spread from the bile ducts to the
blood vessels
lymph vessels and lymph nodes
nearby organs such as the liver or gallbladder
distant organs such as the lungs, bones or abdominal cavity
Early-stage CCA (stages 1 and 2) is often resectable, meaning it can be removed surgically. Stage 3 usually indicates the cancer has spread to nearby structures and/or lymph nodes. Stage 4, the most advanced, involves metastasis to distant organs and is typically unresectable. In such cases, treatment focuses mainly on palliative care to relieve symptoms and improve quality of life.
Cholangiocarcinomas (bile duct cancer) - Treatments
After the CCA is found and staged, your specialist team will discuss your treatment options with you. In choosing a treatment plan, these are some factors to consider:
The location and extent of the cancer
Whether the cancer is resectable (removable by surgery)
The likely side effects of surgery and other alternative treatment
Your overall health and fitness for surgery
The chances of curing the disease, extending life, or relieving symptoms
The main types of treatment for bile duct cancer include:
Surgery
Radiation therapy
Chemotherapy
Palliative therapy
Combination of various treatment options may be offered as well to optimise the treatment results
Surgery
Surgery is often the best treatment for CCA when it is at an early stage and has not spread to nearby blood vessels or distant organs. Other methods have not been shown to be as effective as surgery in treating CCA. However, due to its advanced stage at first presentation, surgery may not be possible for some patients.
As surgery is the only effective method for treating CCA, it is important that a person with suspected CCA has a proper assessment by a specialist team. The specialist team is led by a liver surgeon known as a Hepato-Pancreato-Biliary (HPB) surgeon. When feasible, surgery is a safe and effective in treating CCA.
Depending on the location of the cancer, surgery for CCA includes cutting out the tumour (Liver resection) or Enbloc removal of the bile duct and its surrounding organs and lymph nodes (e.g. Pancreaticoduodenectomy or also known as a "Whipple" procedure or Radical bile duct resection).
Liver transplant
A select group of Intrahepatic CCA patients may be suitable for a liver transplantation.
Clinical trials
Clinical trials test new drugs, surgical techniques and strategies for advancing treatment and care. There may be suitable clinical trials available for selected patients. Please consult your doctor for advice.
Cholangiocarcinomas (bile duct cancer) - Preparing for surgery
Your surgeon will perform a comprehensive evaluation including blood tests, scans to assess if you are suitable for surgery and advise you on the risks involved. This treatment recommendation is based on a consensus of various specialists' opinions (tumour board) weighing the pros and cons of each treatment strategy.
Before surgery, the anaesthesia team will also assess your fitness for surgery and advise you on various aspects of general anaesthesia and pain control after surgery.
Specialist nurses are available to offer pre-surgery counselling.
Cholangiocarcinomas (bile duct cancer) - Post-surgery care
After recovering from your surgery, you will be given regular outpatient appointments with your medical team, which will include blood tests and scans to monitor for any recurrence of cancer.
It is important to follow your doctor's advice, attend clinic visits and tests so that timely treatment can be administered if the cancer or other issues arise.
Cholangiocarcinomas (bile duct cancer) - Other Information
How curable is bile duct cancer?
Bile duct cancer is curable if it is detected early and is suitable for surgical removal. In some cases, a liver transplant may be a potential option for curing CCA. However, this is uncommon as bile duct cancer is often diagnosed at a later stage, when it has already spread to other organs. At that point, surgery alone is no longer a curative option.
What is the survival rate of bile duct cancer?
The prognosis for CCA is generally poor. The 5-year survival rate for CCA cases that has not spread outside of the bile ducts ranges from 15 - 20%. If the cancer has spread beyond the bile ducts or is diagnosed at an advanced stage, the five-year survival rate drops to less than 5%.
Despite the dismal prognosis, there are many new treatment options that are now available such as advancements in molecular profiling and targeted therapies. It is important to note that survival statistics are based on data from past years and may not reflect the improved outcomes associated with these newer treatment options.
Patients should discuss prognosis and treatment choices with their healthcare provider or oncologist, taking into account the diagnosis, stage, type of CCA as well as molecular profiling.
What happens in the final stages of bile duct cancer?
In the final stages of bile duct cancer, when chemotherapy is no longer effective or the patient is unfit for treatment, patients are usually quite frail and weak. Common symptoms associated at this stage include poor appetite, reduced mobility (patients are often bed-bound), jaundice due to liver failure, swelling in the abdomen and lower limbs, pruritus (itchy skin), recurrent fevers and other symptoms related to the spread of disease. Patients eventually decline from organ failure.
Overview
Article contributed by
Hepato-pancreato-biliary and Transplant Surgery
,
Singapore General Hospital
The information provided is not intended as medical advice.
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