Mesothelioma

Epidemiology and incidence

Malignant pleural mesothelioma (MPM) is an aggressive tumour arising from the serosal lining of the chest and abdomen with survival rates of less than one year reported following diagnosis.

♦ Rare—3000 cases per year in UK; the incidence is expected to rise over the next decade before peaking

♦ Caused by asbestos exposure

♦ Other causative agents include — radiation

— thorium dioxide

— silicate fibres

— Simian Virus 40 (SV40), discovered as a contaminant of early poliovirus vaccines

Pathology

Mesothelioma may present as a benign or malignant process. Benign mesothelioma usually presents as an asymptomatic solitary mass and is not typically associated with asbestos exposure. Malignant tumours may be localized or diffuse and are more commonly associated with asbestos exposure and symptoms such as chest pain and dyspnoea. Three distinct malignant subtypes have been identified microscopically:

♦ Sarcomatous

♦ Mixed histologies

Distinguishing mesothelioma from other intra-thoracic malignancies such as adenocarcinoma, requires the assistance of an experienced pathologist. Frequently, light microscopy and standard histochemical stains are inadequate alone. Therefore pathologists use techniques such as electron microscopy and immunohistochemistry to facilitate this distinction.

Clinical and radiological presentation

Mesothelioma can be insidious in its onset with a median time from first symptoms to diagnosis of 2-3 months. Symptoms at presentation commonly include non-pleuritic chest pain and dyspnoea. Constitutional symptoms such as fever, fatigue, and weight loss are seen in

30% of patients. Physical examination frequently demonstrates decreased breath sounds and dullness to percussion due to a pleural effusion or diffuse pleural tumour. Signs of advanced disease are:

♦ Hoarseness

♦ Superior vena cava syndrome

♦ Horner's syndrome

♦ Ascites—heralding abdominal involvement

♦ Lymphadenopathy—an infrequent finding

Laboratory results in mesothelioma are usually unremarkable with no serological tumour marker reproducibly isolated. The radiological presentation of mesothelioma is non-specific. Pleural effusion is common and may be associated with pleural thickening and nodularity. The extent of the pleural mass and encasement of the lung is well demonstarted by CT. However, this imaging modality is less sensitive in detecting mediastinal or transdiaphragmatic involvement.

Magnetic resonance imaging (MRI) of the chest and upper abdomen provides superior definition of tissue planes, in addition to sagittal and coronal views of the diaphragm and thorax apices, and is an important adjunct to staging.

Diagnosis

Thoracoscopy remains the procedure of choice to obtain a pathological diagnosis of malignant mesothelioma, with an 80% diagnostic yield. Thoracocentesis and percutaneous pleural biopsy has a yield of only 30-40%. When thoracoscopy is not possible due to obliteration of the pleural space by the tumour, an open pleural biopsy may be performed. Careful planning of the incision site is essential because mesothelioma has a propensity to implant within chest wall wounds. Exploratory thoracotomy should be avoided.

Table 16.6 Brigham Staging System for malignant pleural mesothelioma

Stage

Description

I

Disease completely resected within the capsule of the

parietal pleura without adenopathy;ipsilateral pleura,lung,

pericardium,diaphragm,or chest wall disease limited to

previous biopsy sites

II

All of Stage I with positive resection margins and/or

intrapleural adenopathy

III

Local extension of disease into the chest wall or mediastinum,

heart,or through diaphragm into peritoneum;or with

extrapleural lymph node involvement

IV

Distant metastatic disease

Staging

In 1976, Butchart proposed a staging system based on the extent of tumour involvement within the chest, but this system correlated poorly with survival. Subsequently, alternative staging systems have been proposed, several based on a TNM concept, although none have gained universal acceptance.

The Brigham staging system provides a straightforward characterization method, based on key disease characteristics, that stratifies survival. In a series of 183 patients treated in a multimodality setting, median survival for patients with stage I, II, and III disease was 25,20, and 16 months respectively.

Accurate pre-operative pathological staging is best achieved by thoracoscopy for pleural evaluation, mediastinoscopy for mediastinal nodal involvement, and laparoscopy to rule out peritoneal seeding or diaphragmatic involvement when indicated.

Treatment

Without treatment, the average patient with MPM survives less than one year from the time of diagnosis. As a result of this poor prognosis various therapeutic options have been explored including:

♦ Radiotherapy

♦ Chemotherapy

♦ Immunotherapy

Individually, each of these modalities has been disappointing when compared to single-modality treatment results. Current experience has shown multimodality therapy to offer improved survival in selected patient groups. Multimodality therapy should be carried out in the context of an approved study protocol by thoracic surgeons experienced in treating this disease.

At Brigham and Women's Hospital, Boston, extrapleural pneumon-ectomy followed by chemotherapy (carboplatin and paclitaxel) and radiotherapy (40.5 Gy) is being used. Recently, 183 patients have been reviewed, demonstrating an overall median survival of 17 months and 2- and 5-year survival rates of 36% and 14% respectively. Positive predictors for improved outcome were epithelial histology, negative resection margins after operation, and negative extrapleural nodal status. Patients with all three positive predictors enjoyed a 51-month median survival with 2- and 5-year survival rates of 68% and 46% respectively.

The following novel therapeutic approaches are currently undergoing active clinical investigation in an effort to improve treatment survival outcome:

♦ Intracavitary, hyperthermic chemotherapy

♦ Immunotherapy

♦ Photodynamic therapy

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