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


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.


CONCLUSIONS
In patients with malignant pleural mesothelioma, intrapleural perfusion hyperthermo-chemotherapy induced potent apoptosis of tumor cells, increasing immediately postperfusion and peaking at 24 h.
Matsuzaki
Yasunori
Y
Department of Surgery, Cardiovascular, Thoracic and General Surgery, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
Tomita
Masaki
M
Shimizu
Tetsuya
T
Hara
Masaki
M
Ayabe
Takanori
T
Onitsuka
Toshio
T
D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D002945:Cisplatin / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced; D007150:Immunohistochemistry; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D009367:Neoplasm Staging; D010477:Perfusion; D016066:Pleural Effusion, Malignant / Q000473:pathology; D010997:Pleural Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D002945:Cisplatin