What is Biliary Tract Cancer?
The biliary tract, which includes the gallbladder and a network of ducts inside and outside the liver, channels bile to the second part of the small intestine at a spot called the major duodenal papilla. This tract is lined with cells known as cholangiocytes. Biliary tract cancer, known as cholangiocarcinoma, develops when these lining cells turn malignant or cancerous. This type of cancer is classified based on where it’s located in the body: 1) inside the liver (intrahepatic cholangiocarcinoma) and 2) outside the liver (extrahepatic cholangiocarcinoma), including a type of tumor named Klatskin tumor, which is found at the point where the right and left hepatic ducts join with the cystic duct to form the common bile duct. This category also can extend to include cancer in the gallbladder, the Ampulla of Vater, which is an opening that allows bile and pancreatic juice to flow into the small intestine, and pancreatic biliary ducts.
Even though intrahepatic and extrahepatic cholangiocarcinomas both start in the lining of the bile duct, they behave differently and affect the body in different ways due to their different locations.
Cholangiocarcinoma is quite rare but tends to be highly aggressive and hard to treat because it is typically discovered at a late stage when it’s too advanced to be removed with surgery. The late diagnosis often means that the cancer has spread extensively to blood vessels and nearby lymph nodes making effective surgical treatment challenging. However rare, cholangiocarcinoma is the second most common kind of primary liver cancer, after hepatocellular carcinoma, which is cancer that starts in liver cells.
What Causes Biliary Tract Cancer?
Chronic (long-term) inflammation can cause the cells of the biliary tract – the path by which bile is released from the liver – to change under stress and transform into cancer cells. The most well-known chronic inflammation condition linked to biliary tract cancer is primary sclerosing cholangitis (PSC). PSC, usually seen in individuals with a chronic bowel inflammation condition like ulcerative colitis, increases the risk of biliary tract cancer.
In addition to PSC, there are other conditions that increase the risk for developing cholangiocarcinoma – a type of cancer that originates in the bile ducts. These conditions cause long-term inflammation and cholestasis (hindrance of bile flow). For instance, infections with liver flukes such as Clonorchis sinensis (frequent in southern China, Hong Kong, and Korea) and Opisthorchis viverrini (common in northeastern Thailand, western Malaysia, and Laos) are risk factors. Hepatolithiasis (the presence of stones inside the liver), chronic infections, and some inherent problems of the biliary tract, like caroli’s disease or choledochal cysts, also pose a risk.
The most common factors related to gallbladder cancer are long-term inflammation of the gallbladder, gallstones, porcelain gallbladder (a gallbladder hardened by calcium), gallbladder polyps, and genetic gallbladder cysts. Obesity, smoking, alcohol use, and type 2 diabetes are also associated with a higher risk of developing cholangiocarcinoma.
Risk Factors and Frequency for Biliary Tract Cancer
Cholangiocarcinoma, a type of cancer, has an annual incident rate of 0.72 to 1.62 per 100,000 people in the U.S. However, these numbers differ around the world, with some countries reporting an increase in cases. Northeast Thailand, for instance, has the highest number of reported cases worldwide, with more than 80 per 100,000 people each year. This high number is mainly due to chronic infection with certain liver flukes which are common in that region.
The rate of a specific type of this cancer, called intrahepatic cholangiocarcinoma, has been on the rise for the last few decades. This increase is believed to be due to several reasons, one of the main ones being chronic inflammation and irritation of the passageways in the liver. The risk of getting this cancer also increases with age and is slightly more prevalent in men. This could be because men are more likely to develop primary sclerosing cholangitis, an illness that is known to increase risk of cholangiocarcinoma, when they are 40 or even younger.
Signs and Symptoms of Biliary Tract Cancer
Cholangiocarcinoma, a type of cancer that affects the bile ducts, often doesn’t show any symptoms in the early stages. When symptoms occur, they’re usually due to the cancer cells blocking the bile duct. The symptoms can include:
- Feeling of pain or heaviness in the upper right part of the stomach
- Jaundice (yellowing of the skin and eyes)
- Itching all over the body
- Fever
- Weight loss without trying
- Feeling unwell in general
- Changes in the color of stool and urine
Testing for Biliary Tract Cancer
When a doctor wants to find the cause of your symptoms, they first perform a thorough physical examination. They then conduct blood tests and may use imaging techniques.
Let’s break down what these tests include:
Blood Tests:
First, they test for the levels of specific enzymes and proteins in your blood. These compounds help monitor whether your liver is disease-free or damaged. This group of tests is commonly known as liver function tests. Some of these tests check the levels of Aspartate aminotransferase (AST) and alanine aminotransferase (AST), which are types of enzymes. In addition, they check levels of a pigment called bilirubin and products excreted in bile, like bile salts, gamma-glutamyl transpeptidase (GGT), and alkaline phosphatase (ALP).
However, please remember that abnormal liver function tests don’t necessarily point to biliary tract carcinoma. These can also indicate many other kinds of liver disease. This is why imaging tests are crucial.
Imaging:
Your doctor will do an ultrasound and a CT scan when you first present with symptoms that might indicate a blockage in your biliary tract. These tests give a comprehensive picture of your anatomy and can play a pivotal role in identifying the location of the tumor.
In some cases, doctors need to look directly at the bile duct. Depending on your situation, they might use either an invasive procedure called endoscopic retrograde cholangiopancreatography (ERCP) or a non-invasive technique called magnetic resonance cholangiopancreatography (MRCP). In some cases, they might also use an endoscopic ultrasound.
The ERCP has a dual purpose: it aids in diagnosis and also provides treatment options. For instance, doctors can take a tissue sample (biopsy) for further testing and also place a stent if required.
Finally, for tissue diagnosis, doctors commonly sample tissue via fine-needle aspiration during the endoscopic ultrasound. Alternatively, they may perform a percutaneous biopsy (a biopsy done through the skin).
In diagnosing cholangiocarcinoma (cancer that occurs in the bile duct), doctors use two common tumor markers named CK7 and CK19. While there are other markers such as carcinoembryonic antigen (CEA) and cancer antigen (CA) 19-9 that are often elevated in malignant (cancerous) biliary diseases, they are not reliable enough to use in general screening for diagnosing cholangiocarcinoma.
Treatment Options for Biliary Tract Cancer
If you have localized bile duct cancer, surgery is usually the only chance for a complete cure. Before the surgery, doctors do physical exams and use scans to understand how big and where exactly the tumor is, whether it has spread to blood vessels or lymph nodes, and whether it has spread to other parts of your body (a process known as metastasis).
In some cases, doctors may use laparoscopy, a type of keyhole surgery, to get a better understanding of the tumor. Extrahepatic cholangiocarcinoma, a type of bile duct cancer that isn’t within the liver, is usually treated with surgical removal of the tumor. This might involve removing part of the liver and bile duct. The aim is to get rid of all the cancer cells. The extent of liver removal depends on how much the liver has been affected by the tumor.
Another subtype of extrahepatic cholangiocarcinoma may involve the pancreatic duct. In these situations, a surgery known as a Whipple’s procedure is performed. In selected cases, liver transplantation has been done after surgical removal of intrahepatic cholangiocarcinoma (cancer in the bile ducts within the liver) for better outcomes.
After the treatment, regular scans are performed to check for any abnormalities in the bile duct after surgery. In cases where all the cancer has been completely removed and there’s no involvement of regional lymph nodes, doctors usually don’t recommend chemotherapy or radiation therapy. However, if the cancer couldn’t be entirely removed or has spread to lymph nodes, then therapy involving 5-fluorouracil, a type of chemotherapy drug, is suggested.
In cases where the cancer is advanced at the time of diagnosis, has spread to other parts of the body, has come back after prior treatment, or in patients who aren’t suitable candidates for surgery, other treatment options are considered. These include chemotherapy, palliative therapy which is aimed at relieving symptoms, immunotherapy which boosts your body’s natural defenses to fight the cancer, and targeted therapy which aims to attack specific cancer cells without harming normal cells. Studies have shown better results when two chemotherapy drugs, gemcitabine and cisplatin, are given together.
For patients who are not suitable for surgery, relieving symptoms like biliary tract obstruction are accomplished using palliative measures, such as stent placement, and chemotherapy. There’s ongoing research to improve survival outcomes with various combination therapies.
Recent research has identified certain faulty genes linked to bile duct cancer. Therapies that target these faulty genes have shown promise and are currently being tested. For example, ivosidenib, a drug that targets faulty IDH1 genes, has displayed cancer-fighting properties and holds potential.
Clinical trials for other targeted therapy drugs are ongoing with promising initial results. For example, bevacizumab, a drug that targets blood vessel growth in tumors, has shown positive results when used together with chemotherapy. Additionally, patients whose tumors can’t be removed and have certain genetic characteristics may be considered for a type of drug called pembrolizumab, which targets and inhibits a protein that cancer cells often use to evade the immune system.
What else can Biliary Tract Cancer be?
When dealing with liver and gallbladder-related problems, physicians would be looking out for the following conditions:
- Liver Cancer (Hepatocellular carcinoma)
- Cancer that has spread to the liver (Metastatic liver cancer)
- Gallbladder growths (adenomas)
- A condition affecting the bile ducts related to an immune system response (IgG4 related sclerosing cholangitis)
- Small, noncancerous growths in the gallbladder (gallbladder polyps)
- A noncancerous condition that creates pockets within the muscle of the gallbladder (gallbladder adenomyomatosis)
- Pancreatic cancer
What to expect with Biliary Tract Cancer
Biliary tract cancer (cancer that occurs in the bile ducts) is particularly severe due to its tendency to be diagnosed late and because treatment options are limited. The prognosis for this form of cancer is very poor, with half of the people diagnosed surviving less than two years and less than 10% surviving after five years.
Various chemotherapy drugs are often used to treat biliary tract cancers that cannot be removed by surgery. However, even with this treatment, the average survival duration is typically a year, which demonstrates the seriousness of this type of tumor.
Surgery is the only potential cure for cancer at a nascent stage. The chances of post-surgery survival depend on various factors like whether the cancerous cells are found at the edges of the tissue removed during surgery (“margin status”), the involvement of the adjacent organs, and if the cancer has spread to other parts of the body (“metastasis”).
Possible Complications When Diagnosed with Biliary Tract Cancer
Complications can arise from chemotherapy, radiotherapy, or surgery when treating biliary tract cancer. Here are some of those potential complications:
Side Effects of Chemotherapy:
- Decrease in white-cell count, platelet count, and hemoglobin
- Hair loss
- Loss of appetite, nausea, fatigue, and vomiting
- Impaired liver and kidney functions
- Infections, with or without a decrease in neutrophils (white blood cells)
- Biliary sepsis, a severe infection in the bile ducts
Complications after Surgery:
- Sepsis, a severe infection that spreads throughout the body
- Respiratory failure or liver failure
- Blood clots (thromboembolic events)
- Abdominal abscesses, wound infections, or major bleeding
- Deep vein blood clots
- Leaking bile from the surgical area
- Reoccurrence of the tumor
Side Effects of Radiotherapy:
- General fatigue
- Nausea and vomiting
- Fever
Preventing Biliary Tract Cancer
When doctors treat patients who have cancer in the biliary tract (the part of your body that produces bile), it’s crucial for them to explain the patient’s condition and treatment in a way that’s easy to understand. This means learning about the disease, how fast it’s growing, the expected outcome, and the patient’s overall health before and after surgery. Doctors should also discuss any potential risks or complications associated with the procedure.
If the cancer has spread to the point that it cannot be removed surgically, or if the patient isn’t suitable for surgery for other reasons, the medical team needs to provide detailed information about the illness and its outcome. They should explain how it might affect the patient both mentally and physically, discuss alternative treatments to surgery, and explain any risks or difficulties these treatments might present, as well as how to handle these complications. The patient’s total wellbeing – including their emotional, social, physical, and mental health – should be the focus of this approach.
