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MESOTELIOMA. Malignant Mesothelioma. Pleural vs. peritoneal Pleural: breathlessness, pleural effusion, chest wall pain or incidentally Peritoneal: distention from ascites, abd. Pain. Causes. Asbestos Long thin fibers: amphiboles (blue): main Ca causer
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Malignant Mesothelioma • Pleural vs. peritoneal • Pleural: breathlessness, pleural effusion, chest wall pain or incidentally • Peritoneal: distention from ascites, abd. Pain
Causes • Asbestos • Long thin fibers: amphiboles (blue): main Ca causer • Feathery fibers: serpentine or chrysotile (white) • Simian virus 40 (SV40): also implicated cofactor (oncogenic virus)
Diagnosis • Diagnosis is made on HISTOLOGY • Cytology: Only in epithelial histotype • A pathology panel is preferred • Clinical information can help
Diagnosis • Cytology: + in >3/4 of cases • Stain + for calretinin, wilms tumor antigen 1 (WT1) determines if mesothelial cells. Ck 5/6 • (adenoCA does not) • Stain for BerEP4/TTF-1 IN ADENOCARCINOMA • Or via histopathology via Bx
Diagnosis • Imaging: • CXR: can show effusion, pleural mass or plaques (not a precursor to cancer) • CT: effusions or mass (pleural based) • Can see thickening of intralobular septum • Can see uniform rind of tumor encasing lung • Can see local tumor mass • Can see invasion into chest wall ~20% usually from a procedure • MRI: good to see extent of tumor particularly when invading into local structures • PET: used to help differentiate benign from malignant pleural lesions and extra thoracic disease (helps with staging)
How deep is your biopsy? Not Diagnostic Diagnostic
Prognosis and Staging • Median survival: from time of diagnosis: 12 months (range 6-18m): for treated patients • survival: from time of diagnosis: 4-13 months: for untreated patients • CT/MRI/PET important in staging pt. • Also role for mediastinoscopy/laparoscopy for staging • Use modified TMN staging system • International Mesothelioma Interest Group • Poor prognosis: thrombocytosis, leukocytosis, low HgB, fever, age>65, poor performance status, male • Good prognosis: epithelial histo, stage 1, age <65, low perform score, no CP, symptoms present > 6 months before Dx
Treatment • Surgery: most useful for palliation and should be combined with radiotherapy or chemotherapy • Chemo: Past response rate <20% • New advances: • Pemetrexed (inhibits dihydrofolate reductase and thymidylate synthase): overall survival increased 11 months • Pemetrexed + cisplatin: increased survival another 3m • Similar response with other combo chemo regimens with 3-6 m increase in addition to single agent • Gemcitabine: subjective improvement • Gleevec and Iressa (block PDGF/EGF): no response • Radiotherapy: palliative relief for pain • Trials with immune and gene therapy on going
Peritoneal mesothelioma • Treatment usually includes surgical cytoreduction • Intraperitoneal chemo • For recurrent or unresectable disease: palliative chemo (pemetrexed and cisplatin)
Palliative treatment • Recurrent pleural effusions: talc application or pleurodesis • Somatic, visceral (organ involvement) and neuropathic pain: • Opiods, nsaids, other