Les HôpitauxLes HôpitauxUniversitairesUniversitairesde STRASBOURGde STRASBOURG

Surgical Treatment of Surgical Treatment of Malignant Pleural DiseasesMalignant Pleural Diseases

Prof. J.M. WihlmProf. J.M. WihlmDepartment of Thoracic SurgeryDepartment of Thoracic Surgery

Université Louis Université Louis PasteurPasteur

Strasbourg, FranceStrasbourg, France

PresentationPresentation

• Malignant fibrous tumorsMalignant fibrous tumors– fibroma, fibrosarcomafibroma, fibrosarcoma

• Malignant pleural effusionsMalignant pleural effusions– metastaticmetastatic– primitiveprimitive

• Diffuse malignant mesotheliomaDiffuse malignant mesothelioma

Malignant fibrous tumorsMalignant fibrous tumors

• Pathologic featuresPathologic features– MacroscopicMacroscopic

• largelarge

• atypical locationatypical location

• necrosis and hemorrhagenecrosis and hemorrhage

– MicroscopicMicroscopic• cellularity, pleomorphism, high mitotic indexcellularity, pleomorphism, high mitotic index

• immunohistochemically: immunohistochemically: B=MB=M

Malignant fibrous tumorsMalignant fibrous tumors

• ClinicClinic– pain, cough, dyspnea, feverpain, cough, dyspnea, fever– hypoglycemia (11%) hypoglycemia (11%) (3% for benign)(3% for benign)

• RadiologyRadiology– non-specificnon-specific– pleural effusion (32%)pleural effusion (32%)– rib erosionrib erosion

Malignant fibrous tumorsMalignant fibrous tumors

• DiagnosisDiagnosis– histologic examinationhistologic examination– chest wall invasionchest wall invasion– recurrencerecurrence

• PrognosisPrognosis– survival : 12% - 45%survival : 12% - 45%– recurrence +++ local, intrapleural, metastasisrecurrence +++ local, intrapleural, metastasis– Complete resectionComplete resection

Malignant fibrous tumorsMalignant fibrous tumors

• Surgical treatmentSurgical treatment– large local excision +large local excision +• pulmonary pediculepulmonary pedicule• parietal pleural pediculeparietal pleural pedicule• chest wallchest wall

• Postoperative therapy :Postoperative therapy :– incomplete resectionincomplete resection

• radiotherapy : radiotherapy : titanium clipstitanium clips

• chemotherapychemotherapy

Malignant pleural effusionsMalignant pleural effusions

• MetastaticMetastatic«Virtually all cancers metastasize to the pleura»*«Virtually all cancers metastasize to the pleura»*

– lung cancerlung cancer– breast cancerbreast cancer

• lymphoma, Hodgkin’slymphoma, Hodgkin’s• melanomamelanoma

• Primitive : Primitive : MesotheliomaMesothelioma

* S.A. Sahn, General Thoracic Surgery, Thomas W. Shields

Malignant pleural effusionsMalignant pleural effusions

• ClinicClinic– dyspnea (exertion), pain, weight lossdyspnea (exertion), pain, weight loss– no symptom : no symptom :

• chest Xray findingchest Xray finding

• physical examinationphysical examination

• RadiologyRadiology– pleural effusionpleural effusion– ipsilateral, bilateralipsilateral, bilateral

Malignant pleural effusionsMalignant pleural effusions

• DiagnosisDiagnosis– pleural fluid : serous pleural fluid : serous bloody, exsudate bloody, exsudate– cytology : 66%cytology : 66%– percutaneous pleural biospy : 46%percutaneous pleural biospy : 46%– thoracoscopy * : 95% thoracoscopy * : 95% – videothoracoscopy : 97%videothoracoscopy : 97%– (exploratory thoracotomy)(exploratory thoracotomy)

: 73%

parietal seeding

* C. Boutin, R. Lodenkemper, Eur Respir J, 1993

Videothoracoscopy

Axillary approach Conversion thoracotomy

videothoracoscopy : intrapleural loculations

Malignant pleural effusionsMalignant pleural effusions

• Prognosis : poorPrognosis : poor– few months : lung, digestive, ovaryfew months : lung, digestive, ovary– few years : breast few years : breast – intermediate : lymphomasintermediate : lymphomas

• Palliative treatmentPalliative treatment• short, efficientshort, efficient• SURGERYSURGERY

• Problem of stage IV lung cancerProblem of stage IV lung cancer « paramalignant »« paramalignant »

Malignant pleural effusionsMalignant pleural effusions

• DecisionDecision

– general conditiongeneral condition– symptomssymptoms– expected survivalexpected survival

Malignant pleural effusionsMalignant pleural effusions

• TreatmentTreatment

• Periodical thoracentesisPeriodical thoracentesis

• Chest tube Chest tube « talc slurry »« talc slurry »

• Thoracoscopy : Thoracoscopy : pleurodesispleurodesis

– talc poudragetalc poudrage

– abrasionabrasion

– pleurectomypleurectomy

• Thoracotomy + pleurectomy Thoracotomy + pleurectomy (decortication)(decortication)

Malignant pleural effusionsMalignant pleural effusions

• Treatment :Treatment :Chest tubeChest tube

(variety)(variety)

AmbulatoryAmbulatory techniquetechnique

Malignant pleural effusionsMalignant pleural effusions

• TreatmentTreatment

• Periodical thoracentesisPeriodical thoracentesis

• Chest tube Chest tube « talc slurry »« talc slurry »

• Thoracoscopy : Thoracoscopy : pleurodesispleurodesis

– talc poudragetalc poudrage

– abrasionabrasion

– pleurectomypleurectomy

• Thoracotomy + pleurectomy Thoracotomy + pleurectomy (decortication)(decortication)

Pericardial window

Videothoracoscopic pericardial windowVideothoracoscopic pericardial window

6 month postop control

Malignant pleural effusionsMalignant pleural effusionsIndications for pleurectomyIndications for pleurectomy

• ConsCons– major surgical proceduremajor surgical procedure

– morbidity (23%)morbidity (23%)– mortality (10-18%)mortality (10-18%)

• IndicationsIndications– survival survival 6 months 6 months– good conditiongood condition– trapped lung trapped lung (CT scan)(CT scan)

– failed pleurodesisfailed pleurodesis

• Diagnostic thoracotomyDiagnostic thoracotomy

Selected patients

Diffuse malignant mesotheliomaDiffuse malignant mesothelioma

• « diffuse malignant mesothelioma is an « diffuse malignant mesothelioma is an uncommon and lethal cancer for which there uncommon and lethal cancer for which there is currently no standard treatment »*is currently no standard treatment »*

• « its biological dehaviour remains an enigma, « its biological dehaviour remains an enigma, and the treatment of this cancer is still and the treatment of this cancer is still controversial »controversial »**

* Valerie W. Rusch, Cornell University, New York

Diffuse malignant mesotheliomaDiffuse malignant mesothelioma Evaluation before treatmentEvaluation before treatment

• Staging system :Staging system :– Butchard (1976)Butchard (1976)– Dimitrov and McMahon (1987)Dimitrov and McMahon (1987)– UICC (1990) : TNM basedUICC (1990) : TNM based– Rusch (1995) : Rusch (1995) : new international TNMnew international TNM

International Mesothelioma Interest GroupInternational Mesothelioma Interest Group

• type of disease progressiontype of disease progression• correlation TNM status correlation TNM status survival survival• outcome & clinical trial analysesoutcome & clinical trial analyses

Diffuse malignant mesotheliomaDiffuse malignant mesothelioma Evaluation before treatmentEvaluation before treatment

• ImagingImaging– Chest XrayChest Xray

–CT scanCT scan, MRI, MRI

– PET scanPET scan

• Video-thoracoscopyVideo-thoracoscopy

• MediastinoscopyMediastinoscopy

• LaparoscopyLaparoscopy

49% distant metastasis at autopsy

Ruffie R, J Clin Oncology, 1989

Diffuse malignant mesotheliomaDiffuse malignant mesotheliomaCT scan imagingCT scan imaging

Diffuse malignant mesotheliomaDiffuse malignant mesotheliomaCT scan imagingCT scan imaging

Diffuse malignant mesotheliomaDiffuse malignant mesotheliomaCT scan imagingCT scan imaging

Diffuse malignant mesotheliomaDiffuse malignant mesotheliomaPET scan imagingPET scan imaging

Diffuse malignant mesotheliomaDiffuse malignant mesothelioma Treatment optionsTreatment options

• SurgerySurgery

• RadiationRadiation

• ChemotherapyChemotherapy

• ImmunotherapyImmunotherapy

• Supportive careSupportive care

• Combined modalitiesCombined modalities

Diffuse malignant mesotheliomaDiffuse malignant mesothelioma Radiation therapyRadiation therapy

• Alone Alone ?? • Associated with surgery Associated with surgery chemotherapy chemotherapy

• Local symptom control Local symptom control (45 Gy)(45 Gy)

• Volume : hemithorax, vital structures Volume : hemithorax, vital structures

• Adjuvant therapy after tumor reductionAdjuvant therapy after tumor reduction• Prevention of parietal tumor implants after Prevention of parietal tumor implants after

thoracoscopythoracoscopyFuture : high-dose ?high-dose ?

Diffuse malignant mesotheliomaDiffuse malignant mesothelioma ChemotherapyChemotherapy

• Phase II studies +++Phase II studies +++ all drugsall drugs

• Response rate : 20% Response rate : 20% (30-40%)(30-40%)

• Problem : inclusion criteriaProblem : inclusion criteria

• « remain disappointing »« remain disappointing »

Future :

Diffuse malignant mesotheliomaDiffuse malignant mesothelioma Chemotherapy : new drugChemotherapy : new drug

– Pemetrexed in combination with cisplatin is the only Pemetrexed in combination with cisplatin is the only treatment with activity proven in phase III trials. It is the treatment with activity proven in phase III trials. It is the first, and only registered chemotherapy for the treatment first, and only registered chemotherapy for the treatment of malignant Mesothelioma.of malignant Mesothelioma.Pemetrexed not only improves survival and response Pemetrexed not only improves survival and response rate but also palliates symptoms and improves quality of rate but also palliates symptoms and improves quality of life and lung function.life and lung function.

41% response 41% response raterate

Nicholas J. Voglelzangl, Nevada Cancer Institute, Las VegasNicholas J. Voglelzangl, Nevada Cancer Institute, Las Vegas

Diffuse malignant mesotheliomaDiffuse malignant mesothelioma ImmunotherapyImmunotherapy

Interferon-alpha 2a : systemic

Interferon-gamma : intrapleural

Diffuse malignant mesotheliomaDiffuse malignant mesothelioma Treatment optionsTreatment options

• SurgerySurgery• RadiationRadiation

• ChemotherapyChemotherapy

• ImmunotherapyImmunotherapy

• Supportive careSupportive care

• Combined modalitiesCombined modalities

Diffuse malignant mesotheliomaDiffuse malignant mesothelioma Surgical treatment (1) : palliativeSurgical treatment (1) : palliative

• Thoracoscopy (video)Thoracoscopy (video)– pleural biopsiespleural biopsies

– palliative treatment : palliative treatment : Talc poudrageTalc poudrage

• Limited pleurectomy Limited pleurectomy • Parietal pleuraParietal pleura

pleurodesispleurodesis

Diffuse malignant mesotheliomaDiffuse malignant mesothelioma Surgical treatment (2) : resectionSurgical treatment (2) : resection

• Pleurectomy-decorticationPleurectomy-decortication

• Extrapleural pneumonectomyExtrapleural pneumonectomy(pleuro-pneumonectomy)(pleuro-pneumonectomy)

* Valerie W. Rusch, Cornell University, New York

* David J. Sugarbaker, Harvard Medical School, Boston

Diffuse malignant mesotheliomaDiffuse malignant mesothelioma Surgical treatment (2) : resectionSurgical treatment (2) : resection

• Pleurectomy-decorticationPleurectomy-decortication

• parietal pleuraparietal pleura• visceral pleuravisceral pleura• hemidiaphragmhemidiaphragm• pericardiumpericardium

• Extrapleural pneumonectomyExtrapleural pneumonectomyEn bloc :En bloc :

• lunglung• parietal pleuraparietal pleura• visceral pleuravisceral pleura• hemidiaphragmhemidiaphragm• pericardiumpericardium

Pleurectomy-decorticationPleurectomy-decortication

Diffuse malignant mesotheliomaDiffuse malignant mesothelioma Extrapleural pneumonectomy : techniqueExtrapleural pneumonectomy : technique

Diffuse malignant mesotheliomaDiffuse malignant mesothelioma Extrapleural pneumonectomy : techniqueExtrapleural pneumonectomy : technique

Diffuse malignant mesotheliomaDiffuse malignant mesothelioma Extrapleural pneumonectomy : mortality Extrapleural pneumonectomy : mortality

AuthorAuthorN. of N. of

patientspatientsEpithelialEpithelial

Cell typeCell type

OperativeOperative

Mortality Mortality %%

2 year 2 year

Survival Survival %%

5 year5 year

Survival %Survival %

Worn (1974Worn (1974 6262 -- -- 3737 1010

Butchart (1976)Butchart (1976) 2929 1111 3131 1010 33

DeLaria (1978)DeLaria (1978) 1111 99 00 2727 --

DaValle (1986)DaValle (1986) 3333 2020 99 2424 66

Rusch (1991)Rusch (1991) 2020 -- 1515 3333 --

Allen (1994)Allen (1994) 4040 2626 7,57,5 22,522,5 1010

Sugarbaker (1999)Sugarbaker (1999) 183183 103103 3,83,8 3737 1414

Diffuse malignant mesotheliomaDiffuse malignant mesothelioma Extrapleural pneumonectomy : resultsExtrapleural pneumonectomy : results

• Mortality : 3,8%Mortality : 3,8% ((Pneumonectomy : 5-10%)Pneumonectomy : 5-10%)

• Factors of improvementFactors of improvement– Patient selectionPatient selection– Preoperative preparationPreoperative preparation– Intraoperative managementIntraoperative management– Postoperative care (PCEA, epidural analgesia)Postoperative care (PCEA, epidural analgesia)– Cell type : epithelial > sarcomatous cellCell type : epithelial > sarcomatous cell– Surgical resection marginsSurgical resection margins– Localized lymph nodesLocalized lymph nodes

– Post-op chemo + radiation therapyPost-op chemo + radiation therapy

31 pts :2-year survival : 68%5-year survival : 46%

Diffuse malignant mesotheliomaDiffuse malignant mesotheliomaMultimodality treatmentMultimodality treatment

MULTICENTER PHASE II TRIAL

Hemithoracic Radiation

Extrapleural Pneumonectomy

Induction Chemotherapy(Pemetrexed + Cisplatin

Biopsy Proven Malignant MesotheliomaStage I-III

ConclusionsConclusions

• Malignant fibrous tumors : Malignant fibrous tumors : recurrencerecurrence

• Malignant pleural effusionsMalignant pleural effusions– metastaticmetastatic– primitiveprimitive

• Diffuse malignant mesotheliomaDiffuse malignant mesothelioma

• SURGERYSURGERY * * multimodality trialsmultimodality trials

VideothoracoscopyVideothoracoscopy

Les HôpitauxLes HôpitauxUniversitairesUniversitairesde STRASBOURGde STRASBOURG