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Eur J Cardiothorac Surg 2007;31:772-778. doi:10.1016/j.ejcts.2007.01.047
Copyright © 2007, European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved
a Division of Thoracic Surgery, University Hospital Zurich, Switzerland
b Institute of Surgical Pathology, Department Pathology, University Hospital Zurich, Switzerland
c Institute of Biostatistics, University of Zurich, Switzerland
Received 4 September 2006; received in revised form 27 December 2006; accepted 4 January 2007.
* Corresponding author. Address: University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland. Tel.: +41 44 255 8802; fax: +41 44 255 8805. (Email: walter.weder{at}usz.ch).
Objective: Local recurrence remains a major problem in the treatment of malignant pleural mesothelioma. The aim of the underlying study was to establish a standardised local recurrence model in rats which enables to study different intrapleural therapies. Materials and methods: Fifty microlitre containing 1 x 106 cells of a syngeneic rat malignant mesothelioma cell line (II-45), established from mesothelioma in Fischer 344 rats exposed to asbestos, were inoculated subpleurally via a left-sided thoracotomy. Tumour size was assessed 6 days later and the tumour nodule completely resected. Evaluation of recurrence at the resection site was performed after 10 days (n = 6) and 6 days (n = 6). The recurrent nodule was histopathologically confirmed. In a second experiment, this new recurrence model was evaluated for the effect of intrapleural therapy with different agents: 4 ml of cisplatin-solution (100 mg2/kg BW), cisplatin combined with the fibrin-based sealant Vivostat®, 4 ml taurolidine 2%, repeated injection of 1 µg of the chemokine CCL-19 at the tumour site and 4 ml povidone-iodine in a dilution 1:10. In a control group, the chest cavity was filled with 4 ml 0.9% NaCl. The primary endpoint was the extent of tumour recurrence. Results: Six days after inoculation, all animals presented a standardised tumour nodule at the injection site of a mean diameter of 5.1 (±0.8) mm. Evaluation of the recurrence after 10 days showed a relapse directly at the resection site, but additional tumour nodules on the ipsi- and contralateral chest wall were found and histologically confirmed. The animals that were sacrificed 6 days after resection of the tumour nodule showed a recurrence only at the resection site with no macroscopic or microscopic evidence of other tumour. Resection of the tumour nodule combined with intrapleural application of the different agents lead to clear reduction of recurrence. The strongest effect was observed after intrapleural application of cisplatin-Vivostat® with significant decrease of the longest, widest and thickest diameter of the recurrence. Conclusions: With this new recurrence model for investigation of malignant pleural mesothelioma in rats, we were able to investigate new intrapleural therapies after pneumonectomy. The intrapleural application of cisplatin-Vivostat® significantly reduced the extent of local recurrence.
Key Words: Mesothelioma • Animal model • Recurrence • Extrapleural pneumonectomy • Intrapleural • Cisplatin
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