Induction of apoptosis by intrapleural perfusion hyperthermo-chemotherapy for malignant pleural mesothelioma

Annals of Thoracic and Cardiovascular Surgery. 2008 Jun;14(3):161-5. [Link]

Matsuzaki Y, Tomita M, Shimizu T, Hara M, Ayabe T, Onitsuka T.

Department of Surgery, Cardiovascular, Thoracic and General Surgery, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.

Abstract

Purpose: Despite extensive clinical research, no effective therapy for advanced malignant pleural mesothelioma has been established. In this study, we induced apoptosis in patients with this disease, using intrapleural perfusion hyperthermo-chemotherapy, a new procedure developed in our surgical department. We then measured the tumorcidal effect.

Material and Methods: Our study included 6 consecutive patients with malignant pleural mesothelioma (stage III: 5; stage IV: 1). Because of the advanced stage of the disease, none of the patients underwent tumor resection or pleurectomy. All patients, however, received perfusion treatment. Tumor cells collected from pleural effusions pre-and at 0, 24, and 48 h postperfusion were examined using an immunocytochemical stain to determine apoptosis. The percentage of positively stained cells was expressed as the apoptotic index.

Results: Preperfusion, the apoptotic index was 3.8% +/- 2.0%, indicating spontaneous apoptosis of untreated
tumor cells. Postperfusion, the apoptotic index at 0, 24, and 48 h was 22.8% +/- 5.15%, 63.8% +/- 8.2%, and 47.8% +/- 6.9%, respectively. The patients had a median survival time of 30 months. No patient morbidity was associated with the perfusion treatment.

Conclusion: In patients with malignant pleural mesothelioma, intrapleural perfusion hyperthermo-chemotherapy induced potent apoptosis of tumor cells, increasing immediately postperfusion and peaking at 24 h.