BILE DUCT CANCER: A RARE AND CHALLENGING CONDITION

Medically Reviewed by Dr. Sony Sherpa (MBBS) - September 23, 2024

Cholangiocarcinoma is a rare type of cancer where the bile ducts, a group of tubes that convey bile from the liver and gallbladder to the small intestine, are affected. Bile helps the body eliminate waste and digest fats. As the cancer grows, it very often leads to bile duct blockage and gallbladder or liver problems. Cholangiocarcinoma is also called bile duct cancer or biliary tract cancer.

Bile duct cancer is frequently discovered in an advanced stage when it has progressed to distant body parts or nearby organs. This makes it difficult to treat and lends itself to a poor prognosis. Available treatments can help control symptoms and improve the life quality in people with cholangiocarcinoma.

Bile Duct Anatomy and Cancer Types

Bile duct cancer can form anywhere inside the biliary tract or biliary tree. The biliary tract starts with the common hepatic duct (inside the liver), which meets the cystic duct (connects the gallbladder) at the top of the common bile duct. The bottom of the bile duct joins the pancreatic duct (connects the pancreas) before forming the ampulla of Vater, which opens into the duodenum of the small intestine.^[1]

Cholangiocarcinoma is classified into three types based on its location in the biliary tract^[2]:

• Intrahepatic Cholangiocarcinoma (IC): This type starts in the hepatic duct.
• Perihilar Cholangiocarcinoma (PC): A perihilar cholangiocarcinoma or Klatskin tumor is an extrahepatic bile duct tumor that forms at the junction between the common hepatic ducts and the cystic ducts (the top of the common bile duct).
• Distal Cholangiocarcinoma (DC): This is an extrahepatic type that begins in the bile duct near the small intestine. These types may impact the gallbladder or the section of the tract that passes through the pancreas or duodenum.

Causes

There is no known cause for bile duct cancer, although it is thought to arise over time due to stress-induced modifications of the biliary tract that occur due to chronic inflammation. In recent years, the three types of bile duct cancers have been shown to be triggered by unique genetic mutations that cause the cancer to develop.^[3]

The number one factors associated with causing bile duct cancer include gallstones, gallbladder lesions, growths or cysts, calcification of the gallbladder (“porcelain gallbladder”), and bile duct infections caused by liver flukes.

Other cholangiocarcinoma risk factors include:

• Primary Sclerosing Cholangitis is closely linked to liver disease, ulcerative colitis, Crohn’s disease, and inflammatory bowel disease.
• Liver cirrhosis
• Bile duct problems present at birth
• Obesity
• Smoking
• Type 2 diabetes
• Autoimmune diseases
• Chronic exposure to certain chemicals or toxins
• Family history of bile duct cancer
• Genetic disorders such as Lynch syndrome and cystic fibrosis

Cholangiocarcinoma Symptoms

Bile duct cancer does not usually cause symptoms in its early stages. As it grows, blocked bile duct symptoms can become apparent, including:

• Jaundice: yellowing of the skin and eyes caused by bilirubin buildup.
• Itching: irritation of the skin
• Abdominal pain: on the right side, below the ribs
• Weight loss: due to loss of appetite, nausea, vomiting, or malabsorption
• General malaise: feeling unwell, tired, or weak
• Fever: due to infection or inflammation
• Night sweats: due to fever or hormonal changes

Fatigue, bloating, edema, digestive issues, or swollen lymph nodes are some other signs and symptoms of bile duct cancer.^[4]

Stools may look lighter or discolored due to a lack of bilirubin, which is normally carried by the bile ducts to the small intestine. Instead, bilirubin excess is excreted through urine, causing it to look darker or even brown.

Bile Duct Cancer Stages

The stages of bile duct cancer are discussed below in accordance with the three types: intrahepatic (IC), perihilar (PC), and distal (DC).^[5]

Stage 1

• IC: The tumor begins to grow in the hepatic duct and is graded on size.
• PC: Is confined to the bile duct up to the liver portion.
• DC: Invades the bile duct wall by less than 5mm.

Stage 2:

• IC: The tumor invades liver blood vessels or metastasizes in the hepatic duct.
• PC: Spreads beyond the bile duct into surrounding fat tissue or towards the liver.
• DC: Grows deeper into the bile duct wall up to 5-12mm.

Stage 3:

• IC: The tumor grows beyond and behind the liver.
• PC: Grows into the hepatic artery or portal vein.
• DC: Extends to a depth beyond 12mm into the bile duct wall.

Stage 4:

• IC: The tumor spreads to other organs and tissues near the liver.
• PC: Completely takes over the portal vein or hepatic artery and nearby structures.
• DC: Disrupts the blood vessels supplying the digestive organs and tract, including the superior mesenteric artery or hepatic artery.

Diagnosis

A physical exam and questions about your medical history will be conducted by your doctor if you exhibit symptoms that could be related to cholangiocarcinoma. Tests are also used to confirm the diagnosis and determine the extent and stage of the cancer.

These tests often include:

• Blood tests: To check liver function, bilirubin, and bile salts levels in the blood, and tumor markers, such as CA 19-9, which indicate the presence and quantity of cancer cells.
• Imaging tests: These give an inside picture of the tumor's size, form, location, and any organs it has spread to locally or far away. Examples include ultrasound, computed tomography (CT) scans, magnetic resonance imaging (MRI) scans, magnetic resonance cholangiopancreatography (MRCP), or positron emission tomography (PET) scans.
• Endoscopic tests: This makes use of a medical device with a light and camera that is inserted into the body, which can examine the bile ducts and take samples of tissue or fluid for biopsy. They may include endoscopic retrograde cholangiopancreatography (ERCP), endoscopic ultrasound (EUS), or percutaneous transhepatic cholangiography (PTC).
• Biopsy: For removal of a small piece of tissue from the tumor or a nearby lymph node for microscopic examination and genetic diagnostics. This can confirm the diagnosis and determine the type and grade of the cancer. A biopsy can be done during an endoscopic test by inserting a thin needle through the skin into the tumor (fine needle aspiration) or with surgery.

Treatment Options

The type, stage, location, and size of the tumor, as well as your general health and preferences, affect the course of treatment for bile duct cancer. The treatment primarily aims to destroy the cancer cells, alleviate bile duct obstruction symptoms, and stop or delay cancer recurrence or spread.

The main types of treatment are discussed below.^[6]

Surgery

This is the only potentially curative treatment for cholangiocarcinoma. Surgery may involve removing part or all of the bile ducts and affected organs to reroute bile and alleviate blockages. However, only a small percentage of people with this cancer are eligible for surgery, as most tumors are too advanced or located in difficult places to be completely removed.

Bile duct surgeries consist of^[7]:

• Bile duct resection: Removal of the affected bile duct and reconnecting the remaining bile ducts to the intestine. Used for cancers that affect bile ducts outside the liver.
• Whipple procedure: The damaged bile duct, adjacent lymph nodes, and a portion of the small intestine and pancreas are removed. It is used for tumors that are near the pancreas and small intestine.
• Biliary bypass: Creates a new route for bile to flow from the liver or gallbladder to the intestine, bypassing the blocked bile duct. Relieves discomfort, jaundice, and itching caused by bile duct blockage.
• Stent placement: Opens a blocked bile duct by inserting a metal or plastic tube (stent) in to keep it open and allow bile to flow. Relieves bile duct blockage symptoms.
• Radiosurgery: Targets and destroys cancer cells in a precise area using high-energy beams of radiation. Treats small tumors that cannot be surgically removed or have recurred after surgery. It may also help resolve symptoms in the context of palliative or end-of-life care.^[8]

Liver surgeries that can help those with cholangiocarcinoma include:

• Partial hepatectomy: The removal of a portion of the liver along with the damaged bile ducts in order to treat hepatic bile duct cancer.
• Hepatic lobectomy: Removal of a whole liver lobe (anatomic section) along with the affected bile ducts. It is used for cancers that have spread inside the liver.
• Liver transplant: Replacing the liver with one from a healthy donor liver. It may be required for cancers that have spread too much inside the liver or are difficult to reach.

Chemotherapy

Chemotherapy involves administering medications to destroy or prevent the growth of cancer cells. Chemotherapy is used^[9]:

• To reduce the size of the tumor before surgery in order to make it easier to remove (neoadjuvant chemotherapy).
• To reduce the risk of recurrence after the surgery (adjuvant chemotherapy).
• As the main treatment for advanced or inoperable tumors (palliative chemotherapy).

Chemotherapy can be given by mouth (orally), by injection into a vein (intravenously), or directly into the liver through an artery (hepatic arterial infusion). In order to give the body time to heal, chemotherapy is typically administered in cycles of three to four weeks. The number and duration of cycles depend on the response and tolerance of the patient.

The most commonly used chemo drugs for cholangiocarcinoma are Gemcitabine and Cisplatin. These drugs are usually given together as a combination therapy. Other drugs that may be used include Fluorouracil (also called 5-FU), Oxaliplatin (Eloxatin), and Capecitabine (Xeloda).

The effectiveness and side effects of chemotherapy may vary from person to person. Chemotherapy frequently causes side effects such as nausea, vomiting, hair loss, exhaustion, low blood cell counts, and an increased risk of infection.

Radiation Therapy^[10]

In radiation therapy, cancer cells are damaged or destroyed using high-energy rays or particles. As with chemotherapy, radiotherapy can be used in the form of neoadjuvant, adjuvant, or palliative radiation therapy.

Radiation therapy can be administered from inside the body (brachytherapy) or from the outside (external beam radiation therapy). These are usually administered in successive doses over the course of weeks to months. A radiotherapy or oncologist will work out a suitable protocol. Chemo can also be combined with radiation therapy (chemoradiotherapy) or radiosurgery to increase its effectiveness.

Some side effects of radiotherapy for cholangiocarcinoma include fatigue, low blood cell counts, skin irritation, nausea, vomiting, diarrhea, and increased risk of infection. Depending on the dose, duration, and type of radiotherapy, the side effects can change. Newer techniques and supportive care are known to help reduce side effects and improve outcomes.

Other Treatments

These are treatments that use heat, cold, electricity, or radiation to destroy cancer cells in the bile ducts, such as:

• Radiofrequency Ablation uses high-frequency electric currents to heat up and get rid of small tumors in the liver.
• Cryoablation uses extreme cold to freeze and remove small tumors in the liver.
• Photodynamic Therapy uses a light-sensitive drug and a laser to activate it to eliminate tumors that block or narrow the bile ducts.
• Selective Internal Radiation Therapy uses tiny radioactive beads to deliver radiation directly to the tumors that have spread inside or outside the liver.

Some of these therapies may be good options for getting rid of leftover tumor cells in the area after surgical removal.

Future Therapies

Immunotherapy, targeted therapy, and many other options^[11] are currently being tested for treating cholangiocarcinoma. These improve the immune’s ability to detect and destroy cancer, as well as target specific receptors that help remove tumors. Treatment-resistant patients have been signing up for trials testing their efficacy, which has already been shown for other types of cancer.

Prognosis and Outlook

The prognosis of bile duct cancer depends on several factors, such as the type, stage, location, and size of the tumor, the treatment received, and the response to treatment. Since most tumors are discovered at an advanced stage and are challenging to cure, the survival rate of bile duct cancer is often low.

According to the American Cancer Society, the American average overall 5-year relative survival rate for intrahepatic bile duct cancer is 9%, and 10% for extrahepatic bile duct cancer. Depending on the stage, survival rates can change: 

• Early Stage: For localized bile duct cancer, the 5-year survival rate is 23% for intrahepatic and 18% for extrahepatic types.
• Intermediate stage: For regional bile duct cancer that has spread outside the bile ducts, the 5-year survival rate is 9% for intrahepatic and 18% for extrahepatic types.
• Late-stage: For distant bile duct cancer that has spread to distant organs and tissues, the 5-year survival rate is 3% for intrahepatic and 2% for extrahepatic types.

Some people may have a better or worse prognosis than others, depending on their specific circumstances. The best rates are cited for those who undergo surgery coupled with chemo or radiotherapy.

Prevention and Management Tips

To prevent or reduce the risk of bile duct cancer, you can:

• Avoid or treat conditions that cause inflammation or infection of the bile ducts.
• Lead a healthy lifestyle that includes a gut-supportive nutritious diet and a balanced exercise plan.
• Get regular check-ups and screenings for bile duct problems or liver diseases.
• Maintain a healthy weight.
• Quit smoking and avoid secondhand smoke.
• Avoid or limit exposure to harmful chemicals.

Conclusion

Bile duct cancer is rare and challenging to treat. It is usually only diagnosed at a very advanced stage, resulting in a poor prognosis. Leading a healthy lifestyle and opting for regular screenings are key for prevention in those at a higher risk. Current treatment options involve surgery coupled with chemo or radiation therapy. With emerging advances in diagnosis and treatment, there are more options and opportunities for people with this condition to improve their outcomes and quality of life.

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