Management of Malignant Pleural Mesothelioma

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Mesothelioma: a global epidemic

Mesothelioma is characterized by a long latent period between exposure to the causative agent, usually asbestos, and subsequent tumor development: 96% have a latent period of more than 20 years [1]. This latency accounts for the delay in the peak incidence of mesothelioma deaths. The numbers of patients with mesothelioma are continuing to rise, despite the regulation of the use of asbestos in most developed countries since the 1980s.

In Europe, 5000 people die as a result of mesothelioma

Asbestos exposure

Greater than 80% of patients develop mesothelioma as a result of exposure to asbestos, which is usually occupational. Since the first report in 1960 from South Africa, numerous epidemiologic studies have confirmed the link between mesothelioma and asbestos exposure, and this knowledge has led to a ban in asbestos use in many countries [11]. Risk of mesothelioma is related to the duration and intensity of the exposure to asbestos (and the type of asbestos), with higher levels being associated

Pathology

The mesothelium consists of a monolayer of mesothelial cells, supported by submesothelial connective tissue [22]. In situ mesothelioma cells are 1 to 4 μm thick and are usually polygonal with a flattened appearance. There are tight gap junctions and desmosomes between mesothelial cells, and the cells seem to be able to synthesize and secrete inflammatory mediators and cytokines in response to stimuli. These are likely to have a key role in the modulation of inflammation in response to cell

Clinical picture

Mesothelioma symptoms are often insidious and nonspecific, which can lead to delay in presentation and in diagnosis. The mean time between symptom onset and diagnosis is 2 to 3 months, but 25% of patients may present more than 6 months after the onset of symptoms [46].

Prognosis

The prognosis of mesothelioma is poor, with an untreated median survival of approximately 9 months, although figures vary depending on the patient's selection group and how survival is calculated. A small proportion of mesothelioma patients follow a more indolent course, and prolonged survival (eg, >10 years), although rare, has been reported [53]. The Cancer and Leukemia Group B prognostic index identified poor performance status, age (>75 years old), chest pain, nonepithelioid histology,

Diagnosis

Definitive diagnosis of malignant mesothelioma is made histologically or cytologically. Although radiology is helpful, diagnosis based on clinical picture or radiology alone is inadequate.

Staging

Staging of mesothelioma is not easy to perform, and it is not justified or necessary in everyday clinical practice. Staging should be performed only if the patient is enrolled in clinical trials to categorize patients and to measure responses to treatment [48]. The necessary staging procedures should be governed by the study protocol.

Several staging classifications for mesothelioma have been suggested. The first, the Butchart classification, was devised in 1976, based on the experience of

Treatment

To date, there is no cure for mesothelioma. Malignant mesothelioma is difficult to treat and different from other malignant tumors for several reasons. It spreads along the serosal surface and infiltrates the underlying vital structures early, so surgery is unable to eradicate the tumor. It often arises from multiple sites on the parietal pleura and involves the visceral pleura early. Patients tend to present late in the clinical course because the symptoms are nonspecific and of gradual onset.

Summary

Malignant mesothelioma is increasing in incidence globally and has no known cure. Its unique clinical feature of local infiltration along tissue planes makes it a difficult neoplasm to manage. There have been few randomized controlled trials regarding treatment options, although these have increased in recent years, and results are eagerly awaited. Patient selection bias, variable inclusion methods, and different measurements of response and survival have hampered the interpretation of the

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