Les Hôpitaux Universitaires de STRASBOURG

1. Les Hôpitaux Universitaires de STRASBOURG

2. SurgicalTreatment of Malignant Pleural Diseases Prof. J.M. Wihlm Department of Thoracic Surgery Université Louis Pasteur Strasbourg, France

3. Presentation • Malignant fibrous tumors • fibroma, fibrosarcoma • Malignant pleural effusions • metastatic • primitive • Diffuse malignant mesothelioma

4. Malignant fibrous tumors • Pathologic features • Macroscopic • large • atypical location • necrosis and hemorrhage • Microscopic •  cellularity, pleomorphism, high mitotic index • immunohistochemically: B=M

5. Malignant fibrous tumors • Clinic • pain, cough, dyspnea, fever • hypoglycemia (11%) (3% for benign) • Radiology • non-specific • pleural effusion (32%) • rib erosion

6. Malignant fibrous tumors • Diagnosis • histologic examination • chest wall invasion • recurrence • Prognosis • survival : 12% - 45% • recurrence +++ local, intrapleural, metastasis • Complete resection

7. Malignant fibrous tumors • Surgical treatment • large local excision + • pulmonary pedicule • parietal pleural pedicule • chest wall • Postoperative therapy : • incomplete resection • radiotherapy : titanium clips • chemotherapy

14. Malignant pleural effusions • Metastatic «Virtually all cancers metastasize to the pleura»* • lung cancer • breast cancer • lymphoma, Hodgkin’s • melanoma • Primitive : Mesothelioma * S.A. Sahn, General Thoracic Surgery, Thomas W. Shields

15. Malignant pleural effusions • Clinic • dyspnea (exertion), pain, weight loss • no symptom : • chest Xray finding • physical examination • Radiology • pleural effusion • ipsilateral, bilateral

16. Malignant pleural effusions • Diagnosis • pleural fluid : serous  bloody, exsudate • cytology : 66% • percutaneous pleural biospy : 46% • thoracoscopy * : 95% • videothoracoscopy : 97% • (exploratory thoracotomy) : 73% parietal seeding * C. Boutin, R. Lodenkemper, Eur Respir J, 1993

17. Videothoracoscopy Axillary approach  Conversion thoracotomy

18. videothoracoscopy : intrapleural loculations

19. Malignant pleural effusions • Prognosis : poor • few months : lung, digestive, ovary • few years : breast • intermediate : lymphomas • Palliative treatment • short, efficient • SURGERY • Problem of stage IV lung cancer« paramalignant »

20. Malignant pleural effusions • Decision • general condition • symptoms • expected survival

21. Malignant pleural effusions • Treatment • Periodical thoracentesis • Chest tube  « talc slurry » • Thoracoscopy : pleurodesis • talc poudrage • abrasion • pleurectomy • Thoracotomy + pleurectomy (decortication)

22. Malignant pleural effusions • Treatment : Chest tube (variety) Ambulatory technique

23. Malignant pleural effusions • Treatment • Periodical thoracentesis • Chest tube  « talc slurry » • Thoracoscopy : pleurodesis • talc poudrage • abrasion • pleurectomy • Thoracotomy + pleurectomy (decortication) Pericardial window

24. Videothoracoscopic pericardial window

25. 6 month postop control

26. Cons major surgical procedure morbidity (23%) mortality (10-18%) Indications survival  6 months good condition trapped lung (CT scan) failed pleurodesis Diagnostic thoracotomy Malignant pleural effusionsIndications for pleurectomy Selected patients

27. Diffuse malignant mesothelioma • « diffuse malignant mesothelioma is an uncommon and lethal cancer for which there is currently no standard treatment »* • « its biological dehaviour remains an enigma, and the treatment of this cancer is still controversial »* * Valerie W. Rusch, Cornell University, New York

28. Diffuse malignant mesotheliomaEvaluation before treatment • Staging system : • Butchard (1976) • Dimitrov and McMahon (1987) • UICC (1990) : TNM based • Rusch (1995) : new international TNM International Mesothelioma Interest Group • type of disease progression • correlation TNM status   survival • outcome & clinical trial analyses

29. Diffuse malignant mesotheliomaEvaluation before treatment • Imaging • Chest Xray • CT scan, MRI • PET scan • Video-thoracoscopy • Mediastinoscopy • Laparoscopy 49% distant metastasis at autopsy Ruffie R, J Clin Oncology, 1989

30. Diffuse malignant mesotheliomaCT scan imaging

31. Diffuse malignant mesotheliomaCT scan imaging

32. Diffuse malignant mesotheliomaCT scan imaging

33. Diffuse malignant mesotheliomaPET scan imaging

34. Diffuse malignant mesotheliomaTreatment options • Surgery • Radiation • Chemotherapy • Immunotherapy • Supportive care • Combined modalities

35. Diffuse malignant mesotheliomaRadiation therapy • Alone ? • Associated with surgery  chemotherapy • Local symptom control (45 Gy) • Volume : hemithorax, vital structures • Adjuvant therapy after tumor reduction • Prevention of parietal tumor implants after thoracoscopy Future : high-dose ?

36. Diffuse malignant mesotheliomaChemotherapy • Phase II studies +++ •  all drugs • Response rate : 20% (30-40%) • Problem : inclusion criteria • « remain disappointing » Future : 

37. Diffuse malignant mesotheliomaChemotherapy : new drug • Pemetrexed in combination with cisplatin is the only treatment with activity proven in phase III trials. It is the first, and only registered chemotherapy for the treatment of malignant Mesothelioma.Pemetrexed not only improves survival and response rate but also palliates symptoms and improves quality of life and lung function. 41% response rate Nicholas J. Voglelzangl, Nevada Cancer Institute, Las Vegas

38. Diffuse malignant mesotheliomaImmunotherapy Interferon-alpha 2a : systemic Interferon-gamma : intrapleural

39. Diffuse malignant mesotheliomaTreatment options • Surgery • Radiation • Chemotherapy • Immunotherapy • Supportive care • Combined modalities

40. Diffuse malignant mesotheliomaSurgical treatment (1) : palliative • Thoracoscopy (video) • pleural biopsies • palliative treatment : Talc poudrage • Limited pleurectomy • Parietal pleura pleurodesis

41. Diffuse malignant mesotheliomaSurgical treatment (2) : resection • Pleurectomy-decortication • Extrapleural pneumonectomy (pleuro-pneumonectomy) * Valerie W. Rusch, Cornell University, New York * David J. Sugarbaker, Harvard Medical School, Boston

42. Pleurectomy-decortication parietal pleura visceral pleura hemidiaphragm pericardium Extrapleural pneumonectomy En bloc : lung parietal pleura visceral pleura hemidiaphragm pericardium Diffuse malignant mesotheliomaSurgical treatment (2) : resection

43. Pleurectomy-decortication

44. Diffuse malignant mesotheliomaExtrapleural pneumonectomy : technique

45. Diffuse malignant mesotheliomaExtrapleural pneumonectomy : technique

46. Diffuse malignant mesotheliomaExtrapleural pneumonectomy : mortality

47. Diffuse malignant mesotheliomaExtrapleural pneumonectomy : results • Mortality : 3,8% (Pneumonectomy : 5-10%) • Factors of improvement • Patient selection • Preoperative preparation • Intraoperative management • Postoperative care (PCEA, epidural analgesia) • Cell type : epithelial > sarcomatous cell • Surgical resection margins • Localized lymph nodes • Post-op chemo + radiation therapy 31 pts : 2-year survival : 68% 5-year survival : 46%

48. Diffuse malignant mesotheliomaMultimodality treatment

49. Conclusions • Malignant fibrous tumors : recurrence • Malignant pleural effusions • metastatic • primitive • Diffuse malignant mesothelioma • SURGERY * multimodality trials Videothoracoscopy

50. Les Hôpitaux Universitaires de STRASBOURG