Intrapleural hyperthermic perfusion with chemotherapy increases apoptosis in malignant pleuritis

Abstract

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.