بسم هللا الرحمن الرحيم

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1 بسم هللا الرحمن الرحيم

2 Updates in Mesothelioma By Samieh Amer, MD Professor of Cardiothoracic Surgery Faculty of Medicine, Cairo University

3 History Wagner and his colleagues (1960) 33 cases of mesothelioma in South African asbestos mining community

4 Incidence Male to Female 3 : 1 5 th - 7 th Decade (2500 new cases of MPM annually in USA of which 2000 are men)

5 Pathogenesis & Biology ASPESTOS Narrow & needle like fibers (carcinogenic & mutagenic) Curled & Pliable

6 Latency period after initial exposure has been reported up to 72 years mean 48.7 years range 14 to 72 years

7 80% of patients with MPM have history of Asbestos exposure. Only 10% of those with asbestos exposure acquire mesothelioma.

8 Other factors may be important in development of MPM either independently or as cofactors e.g. simian virus (sv)-40 Cocarcinogen Poor prognostic factor Chromosomal abnormalities example loss of chromosome 22 Genetic susceptibility

9 Median survival time from symptom onset is Chromosomal abnormalities example loss of chromosome 22 Genetic susceptibility Median survival time approximately from symptom on set is one year one year

10 Clinically RT side 66% LT side 40% Asymptomatic SOB Chest pain Weight loss, anorexia, night sweats

11 Clinically Local invasion pain, dysphagia, svc syndrome, Horner syndrome, vocal cord and diaphragmatic paralysis Death due to infection, respiratoiry failure or symptoms of progressive malignancy

12 Diagnosis and staging Biopsy Thoracentesis (initial diagnosis -unreliable) CT guided biopsy (60% with single & 85% Open biopsy with repeat biopsies) Thoracospic biopsy ( 95 % yield & low complications risk 10%)

13 Diagnosis and staging Biopsy Thoracentesis Open biopsy CT guided biopsy Thoracospic biopsy

14 Pathology Epithelial (50%) tubular, papillary, giant, large cell, small cell, myxoid Sarcomatoid (15%) spindle shaped - Poor prognosis Mixed

15 Immunohistochemical Assays for specific antigens can differentiate Mesothelioma from Mestatic Adenocarcinoma Carcinoembryonic antigen CDI 5 absent absent Epithelial membrane antigen Cytokeratin 5 Cytokeratin 6 Calretinin specific specific specific

16 Staging Butchart classification (abandoned -Lack of Prognostic value) TNM-based staging system (proposed by IMIG) (Impact of tumor and node status on survival ) 1-Using CT scan, MRI 2- Surgical staging is superior to clinical staging VATS staging

17

18 Prognostic Factors Stage of disease is but one of the known variable that influence survival Predictors of reduced survival time: Chest pain, dyspnea, platelet count > weight loss, serum lactic dehydrogenase >500 pleural involvement,low HB level, high WBC, age>75, male gender and sarcomatoid histologic type

19 Two prognostic groups 1. Good prognosis group (1 year survival of 40%) having two or fewer poor prognostic Factors 2. Bad prognosis group Biological makers are elevated in MPM e.g. folate receptor, cyclooxygenase 2 (cox-2) and multidrug resistance proteins 1 and 2

20 Treatment Palliative care Pallialtion of symptoms is the primary goal of most therapy (Dyspnea -Chest pain) Radiation dyspnea &chest wall pain Surgical pleurodesis recurrent plural effusion Chemotherapy improves quality of life

21 Majority of patients with MPM are not candidates for radical resection due to Unrespectable, locally advanced disease Comorbid medical illness Radical surgical resection High risk of severe morbidity & mortality Not proven to have a significant beneficial impact on survival

22 Surgery Thoracoscopy with pleurodesis: Useful in tissue diagnosis and for pleurodesis using talc, Bleomycin or Tetracyclines Pleurectomy / decortication: Removal of visceral,,parictal and pericardial pleura from apex of lung to diaphragam Extrapleural pneumonectomy: aggressive en bloc resection of visceral and parietal pleura, lung, pericardium and epsilateral diaphragm Surgery as a single modality has failed to improve survival

23 Radiation Radiation therapy usually requires a large field (dose limiting) It has a role in disease palliation but has no real impact on survival

24 Chemotherapy Single agent response rates are <20% (doxorubicin) Better resuts with Cisplatin and Carboplatin Combination chemotherapy response rates are >40% (Anthracycline based, platinum based or both)

25 Conclusion Single modality therapy has not been effective in changing the natural history of MPM

26 Conclusion Multimodality regimens involving surgery with radiation, chemotherapy and immunotherapy have been initiated with better outcome especially in patients with epithelial histology, negative resection margins with no metastases to extrapleural lymphnodes. Cisplatin and mitomycin are effective in management of distant tumour recurrence Cisplatin and gemcitabine regimen followed by 54 GY of adjuvant hemthorax radiation have been reported to improve the outcome

27 Don t Trouble Troubles Until Troubles Trouble You Samieh Amer

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