Opitz Isabelle, Lardinois Didier, Arni Stephan, Hillinger Sven, Vogt Peter, Odermatt Bernhard, Rousson Valentin, Weder Walter
Division of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland.
Eur J Cardiothorac Surg. 2007 May;31(5):773-8. doi: 10.1016/j.ejcts.2007.01.047. Epub 2007 Mar 12.
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.
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.
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.
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.
局部复发仍然是恶性胸膜间皮瘤治疗中的一个主要问题。本研究的目的是在大鼠中建立一种标准化的局部复发模型，以便研究不同的胸腔内治疗方法。
通过左侧开胸术在胸膜下接种50微升含有1×10⁶个同基因大鼠恶性间皮瘤细胞系（II-45）的细胞悬液，该细胞系由暴露于石棉的Fischer 344大鼠的间皮瘤建立。6天后评估肿瘤大小，并将肿瘤结节完全切除。在10天（n = 6）和6天（n = 6）后对切除部位的复发情况进行评估。复发性结节经组织病理学证实。在第二个实验中，评估了这种新的复发模型对不同药物胸腔内治疗效果的影响：4毫升顺铂溶液（100毫克²/千克体重）、顺铂与基于纤维蛋白的密封剂Vivostat联合使用、4毫升2%的牛磺罗定、在肿瘤部位重复注射1微克趋化因子CCL-19以及4毫升1:10稀释的聚维酮碘。在对照组中，胸腔内注入4毫升0.9%的氯化钠。主要终点是肿瘤复发的程度。
接种6天后，所有动物在注射部位均出现一个标准化的肿瘤结节，平均直径为5.1（±0.8）毫米。10天后对复发情况的评估显示，在切除部位直接复发，但在同侧和对侧胸壁发现了额外的肿瘤结节并经组织学证实。在切除肿瘤结节6天后处死的动物仅在切除部位出现复发，没有其他肿瘤的宏观或微观证据。切除肿瘤结节并联合胸腔内应用不同药物可明显减少复发。胸腔内应用顺铂-Vivostat后观察到最强的效果，复发的最长、最宽和最厚直径显著减小。
通过这种用于研究大鼠恶性胸膜间皮瘤的新复发模型，我们能够研究肺切除术后新的胸腔内治疗方法。胸腔内应用顺铂-Vivostat可显著降低局部复发的程度。
