MALIGNANT PLEURAL MESOTHELIOMA TREATED IN CLINIC FOR PULMONARY DISEASES AND TUBERCULOSIS “ PODHRASTOVI “ IN TEN-YEAR PERIOD ( FROM 1998 TO 2007 )

Malignant pleural mesothelioma (MPM) is the most common primary malign tumour of pleura. Th e aim of this study was to evaluate cases of MPM diagnosed and treated in Clinic for Pulmonary Diseases and Tuberculosis “Podhrastovi“ during ten-year period (-). Study is retrospective. Th e patients were analysed according to age, sex, histopathologic type of the tumour, cantonal distribution in Federation of Bosnia and Herzegovina and regimen


Introduction
Malignant mesothelioma is a tumour in origin from cells of serous membranes such as pleura, pericard, peritoneum and tunica vaginalis testis. Th e most common localisation is a pleura. Malignant pleural mesothelioma (MPM) almost always has a diff use growth and involves both visceral and parietal surfaces. WHO advises that MPM should be classifi ed into one of three main types: epitheloid, sarcomatoid (with desmoplastic being a particularly aggressive) and biphasic (). Asbestosis fi bres are the cause of the most cases of MPM. About   cases of MPM may be directly attributable to occupational asbestos exposure (,,). MPM can also result from para-occupational (for example-laundering worker's overalls) and environmental exposure (). The mean latency period between fi rst exposure to asbestos and death from MPM is  years (range -) (). Clinical features -Typically, presentation is either with a chest pain, dyspnoea or both (, ). Th e pain is dull, diff use and worsens during the course of illness. It may be described as heaviness or aching in the shoulder arm, chest wall and upper abdomen. It sometimes has neurophatic components because of entrapment of intercostal, autonomic or brachial plexus nerves. Cough is not prominent. Profuse sweating may occur. Pneumothorax is rare. Th e disease spreads by local extension and involves mediastinal structures. Pericardial involvement with tamponade and dysphagia may be pre-terminal events. Bilateral disease and expressive weight loss may be present in the terminal phases. Sometimes patients present with acute pleuritic chest pain and a clear radiographs or a small eff usion and initial investigations may fail to give a diagnosis. Some patients may remain symptom-free for many months, some have rapid deterioration. Th e illness is progressive with a median survival of  - months (, ). Distant metastases are late and more common in the sarcomatoid variety (). Diagnosis-It is essential to use the combination of history, examination, radiology and pathology. Th e history of asbestos exposure is very important. Physical signs include signs of pleural thickening and eff usion with restriction of expansion of the hemithorax. Finger clubbing occurs commonly (). Sometimes tumour tissue may be felt between the ribs. Plain chest radiographic abnormalities may strongly suggest a malignant process. Th e key investigations are pleural tap if an eff usion is present and the fl uid should be sent for cytology and immunocytochemistry; contrast -enhanced CT with a biopsy (). In early phase the pleural fl uid is serous, later it is often hemorrhagic. Although immunocytochemistry can reliably show that cells are mesothelial, it may be diffi cult to distinguish malignant from highly reactive mesothelial cells (). Pathological diagnosis may be obtained from cytology or histology and interpretation should be taken in context with the history, examination fi ndings and radiological appearance. A biopsy is required if the diagnosis is not clear after the pleural tap and CT scan. Th e techniques are an ultrasound or CT -guided percutaneous pleural or a thoracoscopic biopsy. Blind Abram's punch biopsy is less effective (). Th oracoscopy is appropriate where there is a pleural fl uid and it facilitates complete drainage, biopsy and immediate talc pleurodesis. Negative pleural biopsy and cytological results do not exclude MPM. Diagnostic imaging -Th e initial chest radiographic appearances may range from normal in early disease to complete opacification of a hemithorax. Th e pleural thickening may manifest as discrete pleural nodules or pleural plaques visible after the drainage of a fl uid or may encase the lung. Th e mediastinum may be dislocated. Ultrasound -pleural effusions and thickening can be readily appreciated and discrete malignant nodules can be seen (). Contrastenhanced CT (computed tomography) is the primary imaging modality for evaluation of MPM. Magnetic resonance imaging (MRI) features are similar to those seen at CT but both techniques may underestimate the stage of disease. When conventional imaging and biopsy are unhelpful, PET (positron emission tomography) may be useful. As to serum markers, a recent study () confi rmed higher levels of SRMP (soluble mesothelin related proteins) in MPM. Management -Th e role of surgical resection is very uncertain. The more radical is extrapleural pneumonectomy (pleuropneumonectomy)(EPP) than the debulking operation (cytoreductive surgery) performed at open thoracotomy or by video -assisted thoracic surgery (VATS). The TNM staging system proposed by the International Mesothelioma Interest Group (IMIG) is used for assessing patients with potentially resectable disease. One of the central aims is to achieve an early pleurodesis. Th e most eff ective available pleurodesis agent is sterile talc (). Radiotherapy provides pain relief and reduces mass of tumour. Prophylactic radiotherapy may reduce chest wall implantation following invasive procedures. Chemotherapy should be used for all patients with performance status -. Several chemotherapeutic agents can reduce tumour bulk, help symptoms and prolongs survival. Supportive and palliative care of patients provide relief of pain and other physical symptoms such as dyspnoea, cough and others. The aim of this work was to evaluate cases of MPM treated in Clinic for Pulmonary Diseases and Tuberculosis "Podhrastovi" during ten-year period (-).

Materials and Methods
This retrospective study was performed using a database with cases of MPM diagnosed and treated in Clinic "Podhrastovi" from  ¬to . Th e patients were analysed according to age, sex, histopathologic type of the tumour, cantonal distribution and regimen of treatment.

Results
Th e results of our study are showed on the following graphics. MPM presents , (range -, per year) of all hospitalised patients with a malign disease, and the greatest number was in the year  (Graphic ).

Discussion
Th e established cause of MPM is inhalation of asbestos in occupational, para-occupational or environmental exposure. Th e highest risks are in workers in shipbuilding, railway engineering, asbestos product manufacture; but also in subjects with less obvious occupations such as decorator and plumber. Th e risk is higher for amphibole asbestos fi bre type than chrysotile (). Genetic predisposition may explain why fewer than  of asbestos-exposed individuals develop MPM (). MPM can be induced by non-asbestos fi bres such as erionite found in rocks in some areas in Turkey () but only some families within only three villages develop MPM which show the role of genetic factors ().
Our study is retrospective and we were not able to establish real exposure to asbestos fi bres in the past. Between - in Clinic "Podhrastovi"  patients with MPM were hospitalised ( male and  female) which presents , (range -, per year) of all hospitalised malignant patients in that period. Th e relative high number of women indicate the importance of para occupational or environmental asbestos exposure. Patients more than  years old were the most frequent. In the United States there were  mesothelioma cases ( males and  females) in . Th e incidence was , cases of mesothelioma (pleural and peritoneal) per . population (, males; and , females) (). Pathologist should attempt to specify the histological type of MPM but it is often diffi cult (). Histopathology types of hospitalised MPM in our Clinic: epitheloid form (-,); sarcomatoid form (-, ); non diff erentiated (-,). Th erapy of MPM is very uncertain. One of the central aims is to achieve an early pleurodesis which is done in all our patients with sterile talc. Different modalities of therapy are available-surgery, radiotherapy, chemotherapy, or combination. In our patients chemotherapy was predominated (-,) particularly Gemcitabin + Cisplatin shedule (-,); combination of chemotherapy and radiotherapy (-,); radiotherapy (¬-,); palliative simptomatic therapy (-,). Th ere are big expectations from new chemoterapeutic -pemetrexed which has been on trial from the beginning of . Several studies have reported survival data. A series in England showed median survival from symptoms onset of  months and a worse prognosis in sarcomatoid type (). A study in the USA showed that, among  cases, the median survival from onset of symptoms was  and from diagnosis  months (). Th e few patients who survived over  years had epitheloid form (). The median survival for all patients in our study was , months after the diagnosis. In the developed countries such as United Kingdom there are responsibilities of employers of workers, who might be exposed to asbestos, laid out in Control of Asbestos Regulations ().

Conclusion
MPM is the most common primary malign tumour of pleura with a very poor survival because all of therapy modalities have limited results. Th e established cause in the development of disease is exposure to asbestos, but a genetic predisposition has a big role. Preventive measures, such exists in developed countries would be of the greatest signifi cance. Malignant mesothelioma presents , of all hospitalised malignant patients in Clinic "Podhrastovi" in ten-year period (-). Male and female at the age of more  were the most frequent, particularly men. Th e most number of patients came from Sarajevo. Non-diff erentiated patohistological forms were the most frequent. Chemotherapy was predominated form of treatment. MMP should be considered in any patient with either pleural fl uid or pleural thickening, especially if chest pain is present.