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cholangiocarcinoma

What is it ?

Cholangiocarcinoma is a cancer of the bile ducts. It affects the epithelium of the intra or extra-hepatic biliary tree, that is to say the tissue consisting of closely juxtaposed cells forming all of the bile-collecting channels. Bile is a viscous yellowish fluid produced by the liver, hence the possibility of developing intra or extra-hepatic disease.

Despite a prevalence of the disease still little known, cholangiocarcinoma accounts for nearly 3% of gastrointestinal cancers and about 10 to 15% of hepatobiliary 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 confused. Nevertheless, it seems that its occurrence occurs sporadically, ie that affects only certain individuals in a population without the existence of a defined “chain of transmission”.

This cancer can develop at:
– intrahepatic bile ducts. These pathways are formed of small canals (canaliculi), Herring channels and bile ducts. This set of channels meets to form a common right and left channel. The latter leave the liver to form in turn a common extrahepatic canal. A particular form of tumor affecting the junction between the right and left hepatic ducts is called the Klatskin tumor;
– extrahepatic bile ducts, consisting 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 involvement. In addition, clinical manifestations usually occur when the disease is in an advanced stage of development.

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

Symptoms of cholangiocarcinoma

The 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:
– cholestatic manifestations: pale stools, jaundice, dark urine, pruritus, etc. ;
– discomfort
– weight loss;
– a feeling of tiredness and weakness.
In the case of intrahepatic involvement, the disease is defined more through malaise and specific abdominal symptoms such as:
– weight loss;
– anorexia;
– abdominal pain.

Other symptoms may also be associated with the disease:
– fever;
– itches ;
– pain in the upper right of the abdomen.

The disease is defined in several stages:
– stage 1a: the cancer is located inside the bile ducts;
stage 1b: the cancer begins to spread and spread through the lymphatic vessels;
– stage 2: cancer begins to spread through tissues (mainly the liver) and lymphatic vessels;
– stage 3: the cancer is present in metastatic form in the majority of the blood and lymphatic vessels;
– stage 4: cancer spreads to all organs.

The origins of the disease

The exact cause of cancer of the bile ducts is, to this day, still unknown. Nevertheless, the risk factors for the development of cholangiocarcinoma are, for their part, better known.

The cancer comes from mutations within the support of the genetic information of cells: DNA.
These genetic mutations within cells lead to increased development and uncontrolled cell growth those results in the formation of a cell cluster called a tumor.

In cases where the cancer is not diagnosed in time and / or is not treated quickly, the tumor can then grow and spread directly to other parts of the body or via the bloodstream.

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

In addition, the detection of the disease is often carried out at the advanced stage of the tumor.
The tumor can develop at any level along the bile duct and thus block the flow of bile.

Risk factors for cholangiocarcinoma

Although the exact origin of the disease is, to date, still unknown, many of the risk factors associated with the disease are explicit. This is particularly the case of:

  • 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 their narrowing and disrupting normal bile flow);
  • 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 and Clonorchis sinensis;
  • exposure to thorotrast (contrast agent used in X-ray radiographs).

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

  • age; people over the age of 65 are more likely to develop the disease;
  • exposure to certain chemicals. Thorotrast exposure is the most demonstrative 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 (Polychlorobiphenyls). The former was used for a long time as a fireproof material in the construction, building and industrial sectors. PCBs have also often been used in industry and construction. These chemicals are today subject to strict regulations;
  • the presence of hepatitis B or C;
  • the presence of cirrhosis;
  • HIV infection (Human Immunodeficiency Virus);
  • type I and II diabetes;
  • obesity;
  • the tobacco.

Prevention and treatment of cholangiocarcinoma

Different screening tests for bile duct cancer must be performed in order to make the diagnosis of the disease.

  • the blood test is used in the diagnosis of cholangiocarcinoma. Indeed, in the context where a tumor develops in the bile ducts, cancer cells release certain characteristic and identifiable chemical substances through a blood test. Nevertheless, these markers can also be released under other conditions. The presence of these substances is not systematically related to the development of a cancer of the bile ducts;
  • the biliary tract scanner makes it possible to obtain an image of the interior of this part of the body in order to detect any abnormalities;
  • tomography, allows through a series of X-rays of the liver to analyze this organ in more detail through 3-dimensional images;
  • MRI (Magnetic Resonance Imaging), thanks to 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 gall bladder;
  • the biopsy allows the confirmation of the diagnosis.

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

Patient follow-up is done by a multidisciplinary team consisting of a group of specialists (surgeons, oncologist, radiologist, nurses, gastroenterologist, etc.).

The proposed treatments 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 gall bladder, bile ducts or liver.
In Stage 3, the chances of successful treatment depend on the level of involvement of the lymphatic vessels.
Finally, at stage 4, the treatment success rate is relatively low.

The treatment of the disease can result in surgical procedures allowing the renewal of the cancerous tissues: a part of the bile ducts containing the cancerous cells, the gallbladder, certain lymphatic vessels affected or a part of the liver.
Typically, between 20% and 40% of those affected and undergoing surgery survive 5 years or more after the operation.

In the context of abdominal pain, jaundice, etc., the unblocking of the bile ducts is sometimes necessary. This release is achieved using a thin tube passed through the bile ducts.

Radiation therapy is not a common treatment for cholangiocarcinoma, but it can be effective in reducing symptoms and limiting the spread of metastases. There are two types of radiotherapy: external radiotherapy and internal radiotherapy.
In addition, radiotherapy can cause side effects such as nausea, vomiting or significant fatigue.

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

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

To date, treatments for bile duct cancer 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 timely. These are drugs targeting a particular stage of cancer development.

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