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

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.