What is Mesothelioma ?
Mesothelioma is cancer derived from mesothelial cells lining pleural cavities, peritoneum, pericardium and tunica vaginalis. Pleural mesothelioma is most common in all cases of mesothelioma (80% of cases) and asbestos is believed to be one of the causes of pleural mesothelioma. Asbestos is broadly divided into two groups namely serpentine and amphibole, each of which consists of several types of asbestos. Types of crocidolite blue asbestos from the amphibole group are the most common cause of mesothelioma. Other natural fibers such as erionite can also cause mesothelioma. In the past, there have been suggestions that simian virus 40 (SV40) acts as a causative agent of mesothelioma but recent studies have denied its role. The incidence of mesothelioma in the United States increases to 2000 to 3000 cases each year. The predicted death rate from mesothelioma in the UK is estimated at 90,000 in 2050. Japan predicts 100,000 mortality over the next 40 years. The incidence of mesothelioma shows an increasing tendency but the challenge in the treatment of mesothelioma is in diagnostic procedures, disease risking systems, prognostic factor determination and therapy. Today's rapid technological developments make it possible to detect tumor markers at the cellular, extracellular and molecular levels. Current tumor markers can be used to support the diagnosis, determination of prognosis and monitoring of treatment outcomes. The identification of molecular malignant markers is used to detect residual malignant cells (minimal residual disease, MRD) as predictive factors and risk factors for malignancy. This literature review limits discussion on the markers of pleural mesothelioma tumors.
Mesothelioma Pathogenesis
Mesothelioma due to exposure to asbestos has had the incubation period of between 30 to 40 years. Pathogenesis mesothelioma because asbestos is still unclear and highly influenced by the shape of the fiber abscesses. Mesothelioma is generally divided into three types, namely sarcomatoid and biphasic, epithelial, a mix between epithelial and sarcomatoid. Epithelial type is the type most frequently found (50 to 60% of cases) and have a better prognosis than other types. Type sarcomatoid is a rare type (10% of cases) and has average numbers lasting less than one year. Electron microscope examination is raw gold to enforce a diagnosis mesothelioma. Asbestos can cause mesothelioma through four mechanisms. Mechanism of pleural irritation occurs first. Fibers are thin and long (width < 0.25 micrometers and long > 0.8 micrometers) will more easily enter through inhalation into the airway. The fibers penetrate the alveolar epithelium toward the pleural cavity it will happen a recurring irritation of the surface mesothelium and local inflammation occurs. This process can cause scarring or mesothelioma. The second mechanism relates disturbance process of mitosis. The third mechanism is the formation of oxygen radicals. High iron content in asbestos fibers was instrumental in the formation of oxygen free radicals. High iron content in asbestos fibers was instrumental in the formation of reactive oxygen species (ROS), which can cause cell damage recurring. 6 the fourth Mechanism of asbestos can cause persistent kinase-mediated signaling. Asbestos fibers can induce phosphorylation of mitogen-activated protein kinase (MAPK) and extracellular signal-regulatory kinase 1 and 2 and increase the expression of the protooncogene initial response (activator protein 1) on mesothelial cells. Another theory of pathogenesis mesothelioma is asbestos fibers activate nuclear factor kappa-b (NF-kB) and receptors tumor necrosis factor-alpha (TNF-α). Asbestos causes the macrophages release TNF-α which will bind to the receptors or interact with anti-oxidants to activate track race/MAPK/NF-kB. Cytokines TNF-α causes apoptosis mesothelial cells proliferation and at the same time as the compensation mechanism.
Mesothelioma Diagnosed
Clinical symptoms of mesothelioma are not typical, a common complaint that is often felt by the patient is shortness accompanied by chest wall pain. Non-patients who do not complain of any symptoms and abnormalities are found based on radiological abnormalities during routine medical examinations. Complaints about pleural diseases, pleural aging disorders, restrictive and comorbid disorders such as chronic obstructive pulmonary disease and heart disease. Other frequent complaints include weakness, night sweats, and weight loss. These symptoms appear in advanced settings and are associated with a poor prognosis. Other clinical manifestations depend on the location of the metastatic tumor. Not infrequently with swallowing disease, superior vena cava syndrome, Horner syndrome, paralysis of the vocal cords and diaphragms with causes of death from sleep and respiratory failure. An important supporting tool is a radiological examination. From chest X-ray images often pleural effusions, often we find a single nodule and remove on the contralateral pleura may be suspected to be associated with asbestos. The appearance of pleural effusions is more often unilateral and sometimes mass in the pleura. Ultrasonographic examination and thoracic computed tomography scanning (CT scan) are essential for differentiating pleural effusion or pleural thickening and these two checks can be used as biopsies. CT scan gives a diverse picture with a positive percentage (92%), 86% interlobar fissure thickening, 74% pleural effusion, asbestos exposure signs such as plaque 20% Pleural fluid is generally hemorrhagic, pleural fluid cytologic examination plays an important role in the diagnostic process, its positivity ranges from 33-84%. Such frequency is still difficult to distinguish mesothelioma with reactive mesothelioma, pulmonary adenocarcinoma, and other sarcoma groups. With a special stain for mesothelioma, the epithelial membrane antigen (EMA) will give positive results and a negative chorioembryonic antigen (CEA) antigen important to differentiate with pulmonary adenocarcinoma.
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Histopathologic examination is needed when the pleural fluid cytologic results are insufficient to prove mesothelioma. A closed pleural biopsy using an Abram needle gives a positive result in 30-50% of cases but because it often gives discomfort and nonconclusive or inconclusive results are rarely done. Direct biopsy with thoracoscopy, video-assisted thoracic surgery (VATS), open lung biopsy gave a 98% positive predictive rate, with 96% specificity, 90% sensitivity, 88% specific for malignancy with 10% risk of complications. Confirmation with an electron microscope is needed to determine the histological origin of the tissue examined.
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