Cholangiocarcinoma is cancer of the bile ducts. It affects the epithelium of the intra or extra hepatic biliary tree, that is to say the tissue made up of closely juxtaposed cells forming the set of channels collecting bile. Bile is a yellowish viscous liquid produced by the liver, hence the possibility of the development of intra or extra hepatic disease.

Despite a still little known prevalence of the disease, cholangiocarcinoma accounts for nearly 3% of gastrointestinal cancers and about 10 to 15% of hepato-biliary malignancies. There is a slight male predominance in the development of this pathology. In addition, the disease develops on average between 50 and 70 years.

The origin of the development of this tumor is still unclear. Nevertheless, it would seem that its occurrence is sporadic, that is to say that affects only certain individuals within a population without the existence of a defined “chain of transmission”. (1)

This cancer can develop at:

– intrahepatic bile ducts. These pathways are made up of small ducts (canaliculi), Herring ducts and bile ducts. This set of channels come together to form a common left and right channel. These leave the liver to in turn form a common extrahepatic duct. A particular form of tumor affecting the junction between the right and left hepatic ducts is called: Klatskin’s tumor;

– extrahepatic bile ducts, made up of the main bile duct and the accessory bile duct.

The symptoms associated with this type of cancer are different depending on the intra or extra hepatic damage. In addition, clinical manifestations usually appear when the disease is at an advanced stage of its development.

It is a rare disease with an incidence of 1 per 100 people. (000)

Symptoms of the disease appear at an advanced stage and are different depending on the location of the tumor.

Indeed, in the case where the tumor is extrahepatic, the associated symptoms are: (1)

– cholestatic manifestations: clear stools, jaundice, dark urine, pruritus, etc. ;

– discomfort;

– weight loss;

– a feeling of fatigue and weakness.

In the context of intrahepatic involvement, the disease is defined more through discomfort and specific abdominal symptoms such as:

– weight loss;

– anorexia;

– abdominal pain.

Other symptoms can also be associated with the disease: (2)

– fever ;

– itches ;

– pain in the upper right part of the abdomen.

The disease is defined in several stages: (3)

– stage 1a: the cancer is localized inside the bile ducts;

– stage 1b: the cancer begins to spread and spread through the lymphatic vessels;

– stage 2: the cancer begins to spread through tissues (mainly the liver) and lymphatic vessels;

– stage 3: the cancer is present in metastatic form in most of the blood and lymphatic vessels;

– stage 4: the cancer spreads to all organs.

The exact cause of bile duct cancer is, to this day, still unknown. However, the risk factors for the development of cholangiocarcinoma are better understood.

Cancer arises from mutations within the carrier of the genetic information of cells: DNA.

These genetic mutations within cells lead to increased development and uncontrolled growth of cells which results in the formation of a cell clump called a tumor.

In the event that the cancer is not diagnosed in time and / or is not treated promptly, then the tumor may grow larger and spread directly to other parts of the body or by blood flow. (3)

Cholangiocarcinoma is characterized by a tumor affecting the bile ducts. This usually develops slowly and its evolution to a metastatic state is also slow.

In addition, screening for the disease is often done at the advanced stage of the tumor.

The tumor can grow at any level along the bile duct and block the flow of bile.

Although the exact origin of the disease is, to this day, still unknown, many risk factors associated with the disease are explicit. This is the case in particular with: (2)

• the presence of cysts in the bile ducts;
• chronic inflammation of the bile ducts or liver;
• primary and secondary sclerosing cholangitis (necrotizing inflammation of the bile ducts causing them to narrow and disrupting the normal flow of bile);
• ulcerative colitis (chronic inflammatory disease of the large intestine);
• chronic typhoid carriage (development of typhoid fevers whose origin comes from an infectious agent and can be transmitted from one individual to another);
• parasitic infections by Opisthochis viverrini a pair Clonorchis sinensis ;
• exposure to thorotrast (a contrast agent used in x-ray radiographs).

 Other personal factors also come into play in the development of this type of tumor: (3)

• age; people over 65 have a higher risk of developing the disease;
• exposure to certain chemicals. Exposure to thorotrast is the most illustrative example. Indeed, it has been proven that exposure to this chemical agent widely used in radiography, before its ban in the 1960s, increases the risk of developing cholangiocarcinoma. Other chemicals are also involved in increasing the risk of developing the disease, such as asbestos or PCBs (polychlorinated biphenyls). The first was used for a long time as a flame retardant material in the construction, building and industry sectors. PCBs have also often been used in industry and construction. These chemicals are now subject to strict regulations;
• the presence of hepatitis B or C;
• the presence of cirrhosis;
• infection with HIV (Human Immunodeficiency Virus);
• type I and type II diabetes;
• obesity;
• the tobacco.

Different screening tests for cancer of the bile ducts must be performed in order to make the diagnosis of the disease. (3)

• blood test is used in the diagnosis of cholangiocarcinoma. In fact, in the context where a tumor develops in the bile ducts, cancer cells release certain characteristic chemicals that can be identified through a blood test. However, these markers can also be released under other conditions. The presence of these substances is not systematically linked to the development of cancer of the bile ducts;
• the scanner of the bile ducts makes it possible to obtain an image of the interior of this part of the body in order to detect any abnormalities;
• tomography, through a series of X-rays of the liver, allows a more detailed analysis of this organ through 3-dimensional images;
• MRI (Magnetic Resonance Imaging), using a system of magnetic fields and radio waves to obtain an image of the interior of the liver;
• retrograde cholangiopancreatography endoscopy is a means of highlighting more detailed abnormalities of the bile ducts;
• percutaneous transhepatic cholangiography is also used to obtain a detailed overview of the gallbladder;
• the biopsy allows confirmation of the diagnosis.

Most cases of bile duct cancer cannot be cured. However, treatments for the disease are often symptom-specific.

Patient follow-up is carried out thanks to a multidisciplinary team made up of a set of specialists (surgeons, oncologist, radiologist, nurses, gastroenterologist, etc.). (3)

The treatments offered depend on the symptoms as well as the progress of the cancer.

In stages 1 and 2, surgery is possible for the renewal of part of the gallbladder, bile ducts or liver.

In stage 3, the chances of success of the treatment depend on the level of damage to the lymphatic vessels.

Finally, in stage 4, the treatment success rate is relatively low.

Treatment of the disease can result in surgical interventions allowing the renewal of cancerous tissues: part of the bile ducts containing cancer cells, the gall bladder, certain lymphatic vessels affected or even part of the liver.

Typically, between 20% and 40% of people with and undergoing surgery survive 5 years or more after the operation.

Against the background of abdominal pain, jaundice, etc., the unblocking of the bile ducts is sometimes necessary. This release is carried out using a thin tube passed through the bile ducts.

Radiation therapy is not the usual treatment for cholangiocarcinoma, however it can be effective in reducing symptoms as well as limiting the spread of metastases. There are two types of radiation therapy: external beam radiation therapy and internal radiation therapy.

Furthermore, radiotherapy can cause side effects such as nausea, vomiting or even severe fatigue.

Chemotherapy is also used for purposes similar to radiation therapy. Or for the reduction of symptoms, in order to limit the spread of the tumor and increase the life expectancy of the affected subject. Chemotherapy is often combined with radiotherapy. Side effects associated with chemotherapy are also those associated with radiotherapy plus hair loss.

Some research has shown the benefits associated with the combination of two drugs used in chemotherapy (Cisplatin and Gemcitabine).

To date, treatments associated with cancer of the bile ducts are not as effective as those associated with other types of cancer. Therefore, many studies focus on this type of cancer in order to find better ways to treat the disease.

In addition, research into the development of targeted therapies is also current. These are drugs that target a particular stage in cancer development.