MGR REVIEW Malignant Pleural Mesothelioma Depart. Of Pulmonology R3 백승숙

Definition Malignant mesothelioma - Cancer originating from the lining cells (mesothelium) of the pleural and peritoneal cavities, as well as the pericardium Malignant pleural mesothelioma (MPM) - Mesodermally derived neoplastic disease that arises in the pleura - Kills through direct invasion of surrounding structures - Approximately two-thirds of all mesothelioma cases

Epidemiology Asbestos - A naturally occurring fibrous silicate - Main risk of developing mesothelioma Chrysotile ( 백석면 )Crocidolite ( 청석면 )Amosite ( 갈석면 ) 청석면 > 갈석면 > 트레몰라이트 > 백석면

Epidemiology Occupational asbestos exposure - 석면광산, 석면방직공장, 선박업, 자동차 부품공장 Paraoccupational exposure - Women having laundered their husband's overalls Non-occupational "environmental“ exposure - 슬레이트 지붕, 단열재 등의 건물자재, 자동차 부품 - 탈크 (Talc) 함유 베이비파우더, 의약품, 중국산 풍선껌, 가전제품

Epidemiology 영국 1,750 명 사망 / 프랑스 1,550 명 사망 /

Epidemiology 일본의 석면수입과 질병발생 시기

Epidemiology 일본의 석면으로 인한 폐암과 중피종 발생 현황 일본 오사카 (2005 년 ) - 구보타 : 79 명 사망 - 니치아스 ( 일본석면, 단열재 생산 ) : 141 명 사망  2006 년 3 월 석면의 환경 폭로에 의한 폐암, 중피종 환자를 구제하는 법률 제정

Epidemiology 우리나라의 석면으로 인한 중피종 발생 현황

Epidemiology 부산의 석면방직공장 A C B

Epidemiology Building infrastructure for asbestos related studies Drawing up plan to compensate asbestos victims Laying out environment management plan

Pathogenesis Angiogenesis Primary cancer Local invasion Metastasis Irritation and inflammation Disrupt the function of cellular structures Produce free radicals - damage DNA Produce oncoproteins Irritation and inflammation Disrupt the function of cellular structures Produce free radicals - damage DNA Produce oncoproteins

Clinical description

Diagnosis The combination of accurate history, examination, radiology and the acquisition of pathology is essential Careful history of asbestos exposure is essential Identification of at-risk occupations are strong markers of exposure Occurs predominantly in men, in the 6 th through 8 th decades In those patients with a pleural effusion, sampling of the fluid for cytological examination is the first step

Diagnosis Chest radiographic Continuous, irregular pleural shadowing which extend up both chest walls CPA blunting (80% to 95%) Unilaterally (95%) Right (60%) Continuous, irregular pleural shadowing which extend up both chest walls CPA blunting (80% to 95%) Unilaterally (95%) Right (60%)

Diagnosis Intravenous contrast-enhanced CT Distinguishing malignant from benign pleural dis. 1) Circumferential pleural rind 2) Nodular pleural thickening 3) Pleural thickening of >1cm 4) Mediastinal pleural involvement Distinguishing malignant from benign pleural dis. 1) Circumferential pleural rind 2) Nodular pleural thickening 3) Pleural thickening of >1cm 4) Mediastinal pleural involvement

Diagnosis Positron emission tomography (PET) - Increased the accuracy in diagnosing nodal, distant metastases - Useful in distinguishing malignant from benign pleural disease mean SUV 6.5 vs. 0.8

Diagnosis Pathological findings Blind core needle Bx.(33%)<CT-guided core needle Bx.(87%)<VATS(95%) Epithelioid(50%) / Sarcomatoid(16%) / Biphasic(34%)

Diagnosis Immunohistochemistry - mesothelin, cytokeratin 5/6, calretinin, vimentin, thrombomodulin

Diagnosis Serum markers Osteopontin - Sensitivity ; 77% and specificity ; 85% Soluble mesothelin related proteins (SMRP) - Sensitivity ; 80–83% and specificity ; 80–100% - Mostly associated with the epithelioid sub-type - MESOMARK (Fujirebio Diagnostics Inc, Malvern, PA,USA) Megakaryocyte Potentiating Factor (MPF) - Monitoring of treatment response in mesothelioma

Diagnosis International Mesothelioma Interest Group (IMIG) - TNM-type system

Diagnosis

Management Multimodality treatment - Cytoreductive surgery, chemotherapy and radiation therapy - Prolong survival for select patients with early-stage disease The general treatment strategy - Management of pleural effusions - Palliation of symptoms and end-of-life care - Compensation issues

Management Surgical procedures (1) VATS talc pleurodesis, (2) Pleurectomy/Decortication (P/D) (3) Extrapleural pneumonectomy (EPP) 1.Diagnostic tool, yielding tissue for histological diagnosis 2.Drainage of effusion and pleurectomy decortication improves the quality of life and may increase survival as well

Management Chemotherapy Cisplatin plus Pemetrexed (Alimta; Eli Lilly) - Statistically significant survival advantage vs cisplatin alone

Management Targeted therapy Ongoing trials and future perspectives

Management Prognosis and survival - Median survival varying between 8 and 14 months Good prognosis - epithelial subtype, good KPS, early-stage tumor - The histologic subtype and stage of the tumor  not related J Thorac Oncol Nov;4(11): Good prognosis - epithelial subtype, good KPS, early-stage tumor - The histologic subtype and stage of the tumor  not related J Thorac Oncol Nov;4(11):