Local recurrence model of malignant pleural mesothelioma for investigation of intrapleural treatment.
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.


METHODS
Fifty microlitre containing 1 x 10(6) 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 (100mg(2)/kg BW), cisplatin combined with the fibrin-based sealant Vivostat, 4 ml taurolidine 2%, repeated injection of 1 microg 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.
Opitz
Isabelle
I
Division of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland.
Lardinois
Didier
D
Arni
Stephan
S
Hillinger
Sven
S
Vogt
Peter
P
Odermatt
Bernhard
B
Rousson
Valentin
V
Weder
Walter
W
D000818:Animals; D000891:Anti-Infective Agents, Local / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D045744:Cell Line, Tumor; D054415:Chemokine CCL19; D019742:Chemokines, CC / Q000627:therapeutic use; D002945:Cisplatin / Q000627:therapeutic use; D003131:Combined Modality Therapy / Q000379:methods; D004195:Disease Models, Animal; D015718:Fibrin Tissue Adhesive / Q000627:therapeutic use; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy* / Q000601:surgery; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000601:surgery; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000601:surgery; D011013:Pneumonectomy / Q000379:methods; D011206:Povidone-Iodine / Q000627:therapeutic use; D051381:Rats; D011916:Rats, Inbred F344; D013654:Taurine / Q000031:analogs & derivatives / Q000627:therapeutic use; D013829:Thiadiazines / Q000627:therapeutic use
D000891:Anti-Infective Agents, Local; D000970:Antineoplastic Agents; D054415:Chemokine CCL19; D019742:Chemokines, CC; D015718:Fibrin Tissue Adhesive; D013829:Thiadiazines; D013654:Taurine; D011206:Povidone-Iodine; C012566:taurolidine; D002945:Cisplatin