Mesothelioma
The mesothelioma is a form rare and virulent of Cancer of surfaces mésothéliales which affects the coating of the Poumon S (the Plèvre), of the abdominal cavity (the Péritoine) or wraps it Cœur (the Péricarde). The mesothelioma is caused by the exposure to mineral fibers (like the Amiante, or the érionite). Some were exposed there to their work; others secondarily by family members who, to their knowledge, brought back fibers to the house of their work in their clothing or their Cheveux or on their Peau.
Occurred of this disease, sometimes qualified cancer of the Asbestos , this fiber being the independent factor of risk recognized for this type of cancer, is not indicative of a minimal threshold of exposure and its medical care has an impact limited on the life expectancy of the patients, in general from 12 to 18 months.
The first demonstrations found with the clinical examination are thoracic pains, often associated with breathlessness and épanchement pleural repeating, in general hemorrhagic. The latency time between the first exposure and the development of the mesothelioma is seldom lower than 20 years, often about 30 to 40 years, even more. It does not seem to exist of value threshold of exposure in connection with a risk of appearance.
It was described cases of pleural mesotheliomes occurring in the home environment near to the workers exposed to asbestos, the subjects being exposed because of contamination of the buildings of dwelling or during the maintenance of dusty clothing.
The Tabac plays a synergic part of cofactor in the risk of occurred of a mesothelioma.
Signs and symptoms
Diagnosis
some key words: Radiography of the thorax pulmonary functional tests. CT-scan (or CAT-scan) or MRI Cytology so much of liquid Biopsy Histopathologie Thoracoscopie Laparoscopie
Tests of orientations
There is no protocol universally recognized for the tracking of the people who were exposed to asbestos. However certain research indicates that the level of Ostéopontine in the serum the force of is useful in the tracking of the mesothelioma at the exposed people. The level of soluble protein related to the mesothelin is high in the serum at approximately of 75% of the patients whose diagnosis was confirmed and it was suggested that it could be useful for tracking.
Assessment and evaluation
Once the diagnosis is confirmed, the doctor will have to evaluate the pathological rank of the tumor to establish a therapeutic strategy treatment. The mesothelioma is described as localized if cancer is found only on the surface of the pleural membrane where it began. It is classified as advanced if there exists an extension beyond the original surface of the plèvre to other parts of the body, such as the ganglia lymphatic, the lungs, the thoracic wall, or the abdominal bodies.
Physiopathology
The Mésothéliome is composed of only one and thin layer of cubic cells forming a epithelium bordering the séreuses cavities of the body including/understanding the Péritoine, the Péricarde and the Plèvre to form a virtual cavity. The mineral fiber deposit in the pulmonary parenchyma can have as consequence their penetration in the visceral plèvre from where the fiber can then gain pleural surface, and of this fact of leading to the development of the malignant plates mésothéliales. The driving process with the development of the mesothelioma péritonéal remains unsolved, although it was suggested that asbestos fibers coming from the lung can be transported towards the associated abdomen and bodies via the lymphatic Système. Moreover, the mineral fibers can be deposited in the intestine after the ingestion of contaminated spittles.
It was shown that the contamination of the plèvre by asbestos or other mineral fibers, can induce carcinogenesis. Asbestos the long ones and thin fibers (blue asbestos, Amphibole S) are carcinogenic the more effective than “feathery fibers” of (the Chrysotile (or white asbestos). In the rats the development of a mesothelioma was caused by the intrapleural phosphorylées chrysotile fiber inoculation. It was suggested that at the man, the transport of fibers until the plèvre would be the critical stage in the pathogenesis of the mesothelioma. This assumption is consolidated by the surge observed of a significant number of Macrophage S and other cells of the Immune system towards the localized lesions caused by asbestos fibers accumulated in the pleural cavities and péritonéales of the rats. These lesions continent to be attracted and of the macrophages in great number while the disease progresses, and the cellular changes inside the lesion lead to a tumor whose morphology has all the characters of malignity.
The experimentation suggests obviously that asbestos acts as carcinogenic complete in the development of the mesothelioma which occurs by sequential stages of initiation and promotion. The underlying molecular mechanisms the malignant transformation of the normal cells mésotheliales in the presence of asbestos fibers remain open rather obscure in spite of the demonstration of the oncogenes possibilities of the substance. However, the transformation in vitro of cells mesotheliales human normals into cells of malignant phenotype after exposure to asbestos fibers was not still carried out. Generally it is thought that the asbestos fibers exert their cancerogenic effect via direct physical interactions with the cells of mesothelium in conjunction with indirect effects with interaction with inflammatory cells such as the macrophages. The studies comprising the intrapleural inoculation or intrapéritonéale of various types of asbestos fiber in the rats and the mice established that the long and thin fibers are responsible for a higher incidence of the mesothelioma than short fibers and than the cells phagocytent and store the longest fibers more effectively than of short fibers. In the same way, the incubation of cells of Syrien hamster with glass fiber of which the average length was of 9.5µm caused transformations cellular with a speed identical to that of the Crocidolite. The reduction length of these fibers to obtain an approximate dimension of 2,2 µm reduced the cellular capacity of transformation of a factor 10 to 20 while a more important reduction with less 1µm completely removed the capacity of cellular transformation by the glass fiber particles.
The analysis of the interactions between asbestos fibers and the DNA showed that the phagocytées fibers can come into contact with the Chromosome S, the fibers member often with the Chromatine or are gotten mixed up in the chromosome. This contact between asbestos fiber and proteins of structure of the double helix of the chromosome can induce complex anomalies. The most common anomaly is the Monosomie chromosome 22. Other frequent anomalies include/understand the rearrangement of the structure of the arms of 1, 3rd, 6th, and 9th pairs of chromosomes.
The genetic anomalies most common in the cellular lines of mesothelioma include/understand the délétion of the genes suppressors of following tumors:
- standard Neurofibromatose 2 with 22q12
- P16INK4A
- P14ARF
- Inactivation of the genes suppressors of tumor
- Activation of genes Oncogene S
- Activation of proto-oncogenes because of the incorporation of foreign DNA containing a gene Promoter
- Activation of the enzymes of repair of DNA, which can be inclined with errors.
- Activation of the Télomérase
- Prevention of the Apoptose
It was shown that the asbestos fibers could change the function and the secretary properties of the macrophages, finally creating conditions which support the development of the mesothelioma. After having phagocyte the asbestos fibers, the macrophages produce increased quantities of radical hydroxyl which are the normal by-products of the anaerobic cellular metabolism. However, these free radicals are also known like clastogene and also agents having an action on the membrane to support the cancerogenic effect of asbestos. These oxidants can take part in the process oncogene directly and indirectly while acting on the DNA, by modifying the membrane cellular by various mechanisms, including the activation of oncogenes and the disturbance of antioxydant cellular defenses. Asbestos can also have immunosuppressive properties . For example, it was shown that the chrysotile fibers decrease the proliferation in vitro of the peripheral lymphocytes stimulated by the phytohemagglutinines, remove the lysis of the natural tueuses cells and significantly reduce the viability and the renewal of the tueuses cells activated BY the lymphokines. Moreover, the genetic changes of the macrophages activated by asbestos can have like consequence the production of substances effective mitogenes on the cells mesotheliales like the plate Growth factor (PDGF) and the Growth factor of transformation - the β (TGF-β) which has its turn, can induce chronic stimulation and the proliferation of the cells mesotheliales after lesions caused by asbestos fibers.
Epidemiology
Incidence
Although the reported incidence rates increased these 20 last years, the mesothelioma is always a relatively rare cancer. The incidence is roughly of a case for a million inhabitants. By comparison, the populations with a level of high nicotinism can reach the incidence of more than thousand Lung cancer per million inhabitants. The incidence of the malignant mesothelioma currently reaches a level from approximately 7 to 40 cases by 1.000.000 inhabitants in the Western nations industrialized, according to the importance of the exposure of the populations to asbestos during the last decades. It was estimated that the incidence in the United States could reach one to 15 per 1.000.000 inhabitants in 2004. One expects that the incidence continues to increase in other areas of the world. The mesothelioma more often occurs at the men than among women and the risk increases with the age, but this disease can appear among men or women at any age. Roughly a fifth with a third of all the mesotheliomes are tumors péritonéales.
One can note that an epidemic of mesothelioma was discovered in three villages Turkish (Karain, Tuzkoy and Sarehidir) located in Cappadoce. It is responsible today for 50% of the deaths over there.
Risk factors
The professional exposure to the Amiante is the principal risk factor for the mesothelioma. A past of exposure to asbestos exists in almost all the indexed cases. However, the mesothelioma was reported in some cases of individuals without exposure known to asbestos.
Asbestos is the name of a group of ores which are appeared naturally as a hard fiber agglomerate and flexible devices which can be separate out of thin wire and be woven. Asbestos was employed usually in many industrial products, including cement, of, the shingle brake linings of roof, floor covering, textiles, and products of insulation. So of tiny asbestos particles float in the air, particularly during the manufacturing process, they can be inhaled or swallowed, and present serious health issues. In addition to the mesothelioma, the exposure to asbestos increases the bronchial risk of cancer, causes the asbestose a pulmonary fibrosis (noncancerous chronic disease), and other cancers, like the tumors of the larynx and the kidney. For a person the association of the nicotinism and exposure to asbestos increases the risk significantly to develop a cancer of the higher air routes or a bronchial carcinome. The Kent mark used asbestos in its filters for cigarettes during some of its first years of production in the years 1950 and some cases of mesothelioma resulted from it. Apart from this particular case, the nicotinism does not seem to increase the risk of mesothelioma. Some studies suggest that the Virus simien 40 (SV40) could act like Cofacteur in the development of the mesothelioma.
Exposure to asbestos
The professional sectors having led to exposures to asbestos related to the units of extraction, and industries employing of asbestos because of its properties.
-
units of extraction (mines and mills, in order to prepare fibers of gauge given),
-
manufacture of materials containing asbestos: manufacture of asbestos cement, textile asbestos, materials of friction (brakes, clutches),
-
insulation (in the building, in the clothes industry of industrial furnaces, manufacture of the thermal and refrigerating material, in the shipyards) and heat insulation (flocking with products containing of asbestos is interdict in France since 1977),
-
use of asbestos like heat protection (gloves, aprons, cords, covers…) in various industries: shipyards, Iron and steel industry, Foundry, manufacture of Glass, construction trade,…
Since the prohibition of manufacture of importation and material marketing containing of asbestos in France (decree 96-1133 of the 12/24/1996), it is the intervention in particular on materials in place containing of the asbestos which constitutes major concern, at all the professionals of the building (work of asbestos withdrawal).
-
Guide of location of the exposure to asbestos
Treatment
The treatment of the mesothelioma by conventional therapies did not prove its effectiveness and the patients have one duration Médiane of survival from 6 to 12 months after the diagnosis. The degree of malignity of the tumor depends on several factors of which total surface mesotheliale of the pleural cavity whose importance supports local metastases by the means of the exfoliées cells, as well as the invasion of subjacent fabrics and other bodies in the pleural cavity. Another factor which intervenes is the extremely long latency period between the exposure to asbestos and the development of the disease.
Surgery
There exist two types of surgery. The lighter partial pleurectomy and the widened pleurotectomy which consists have to withdraw the plèvre and a pulmonary block. In certain cases, the surgery can, significantly, increase the hope of survival.
Radiotherapy
Chemotherapy
In February 2004, the Food and Drug Administration approved the use of the Pemetrexed for the treatment of the malignant pleural mesotheliomes. The use of this drug is authorized in France since 2005.
Immunothérapie
The protocols of therapeutic comprising a treatment by immunothérapie gave variable results. For example, the inoculation intrapleural of Bacillus Calmette-Guerin (BCG) in order to try to amplify the immune reaction, proved not to bring any benefit to the patient (while it can improve the state of the patients reached of Cancer of the bladder). It was proven in vitro that the cells of mesothelioma were destroyed by lymphocytary cells after activation by the Interleukine -2 (IL-2), but the patients undergoing this particular therapy felt major side effects. Indeed, this therapeutic test was stopped because of the levels unacceptable lies high of the toxicity of the IL-2 and the severity of the side effects such as the fever and the cachexy. Nevertheless, other tests using the interféron alpha proved to be encouraging with 20% of patients presenting a reduction higher than 50% of the tumoral mass associated with tiny side effects.
Heated Intraoperative Intraperitoneal Chemotherapy
Seek
Legal aspects
See also asbestos and the law = Asbestos and the law
History
An article published by Wagner and coll in 1960 established for the first time that the mesothelioma was a disease resulting from the exposure to asbestos in the form of crocidolite. The article indexed more than 30 cases of the patients who had presented a mesothelioma in South Africa of which momentary exposures and cases concerning of the minors.
In 1962, Doctor McNulty reported the first case of malignant mesothelioma diagnosed in Australia in a workman exposed to asbestos. The workman had worked in the mill with the asbestos mine of Wittenoom of 1948 to 1950.
In the town of Wittenoom, waste of asbestos packing of the mine was recycled for the coating of the courses of recreation and the adventure playgrounds.
In 1965 it was established in a article published in the British newspaper of occupational medicine that people who had lived in the vicinity of the factories and the asbestos mines, but without working there, had contracted a mesothelioma.
In spite of the proof that dust associated with the exploitation of the asbestos mine and with the crushing of fibers was well the cause of the diseases related to asbestos, the started extraction with Wittenoom in 1943 continued until 1966.
It is difficult to include/understand why one allowed the mine and the mill initially to open then to continue to function without with measurements adapted to control the risk; and why nothing was done to force owner (CSR) to put itself at the standards, to adopt surer work methods or to put an end to the operations.
In 1974 the first public warnings concerning the dangers of blue asbestos were published in the bulletin of an Australian magazine in the form of a book connected whose cover was entitled: “this killer is it in your house? ”
In 1978 the government of Western Australia decided to shave the town of Wittenoom, after the publication of a booklet of the department of health, “the health hazard with Wittenoom”, containing the results of the taking away of atmosphere and an evaluation of the medical data available universally.
In 1979 the first complaints for negligence with Wittenoom were launched against CSR and its subsidiary company ABA, and the company of the asbestos diseases was made up to represent the victims of Wittenoom.
References
External bonds
- Mesothelioma-Bases a guide on the Mesothelioma, the disease, the causes, the symptoms, the treatments and last information.
- Incidence of the mesothelioma
- Mésothérapie specific systematized
- Site on the mesothelioma
- Mesothelioma: Questions and answers of the " National Institute" Cancer;.
- American Cancer Society
- Mesothelioma Applied Research Foundation
- Cancer.gov: Does malignant mesothelioma
- Mesothelioma
- What cause the mesothelioma?
- CancerBACUP: Mesothelioma Information Centers
- Medlineplus: Mesothelioma
- Worksafe, Western Australia
| Random links: | Isostasy | Jump | Beijing Hyundai | Untied belladonna | Ichirō Mizuki | Extrémité_de_Petsoe |