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

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.

Intrapleural hyperthermic perfusion with chemotherapy increases apoptosis in malignant pleuritis.

BACKGROUND: Previously, we reported on the effectiveness of intrapleural hyperthermic perfusion with chemotherapy, a new treatment we developed for patients with malignant pleuritis. The present study analyzes the mechanism of the effectiveness of this therapy by examining the induction ratio of apoptosis among tumor cells following the perfusion treatment. METHODS: This study included 11 consecutive patients with primary pulmonary adenocarcinoma and accompanying pleural seedlings and pleural effusions containing tumor cells but without distant metastasis. All patients underwent surgical resection of the primary lesion and then received sequential perfusion treatment. Tumor cells collected from the effusion both before and again at 24 hours following the perfusion treatment were subsequently examined using an immunocytochemical stain to determine apoptosis among tumor cells. The percentage of positively stained cells was expressed as the apoptotic index. We compared the survival rate of these 11 patients with the survival rate of a second group of 11 patients with malignant pleuritis who underwent surgical resection of the primary lesion but who did not receive the perfusion treatment (control group). RESULTS: The ratio of spontaneous apoptosis of untreated tumor cells was 2.8% +/- 2.0%. Following the perfusion, apoptosis among tumor cells was 25.2% +/- 4.6%, clearly a significant increase. While the median survival time for patients receiving the perfusion treatment was 20 months, the median survival time for the control group was 6 months. CONCLUSIONS: In patients with malignant pleuritis, intrapleural hyperthermic perfusion with chemotherapy induced potent apoptosis of tumor cells in the pleural cavity and also improved the survival rate of these patients as compared with patients who did not receive the perfusion treatment.