Hyperthermic Isolated Limb Perfusion with TNF alpha and Cisplatin in the Treatment of Osteosarcoma of the Extremities: A Feasibility Study in Healthy Dogs.
Hyperthermic Isolated Limb Perfusion with TNF alpha and Cisplatin in the Treatment of Osteosarcoma of the Extremities: A Feasibility Study in Healthy Dogs.
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作者：
Van Ginkel RJ;Van Berlo CL;Baas PC;Koops HS;Stuling RV;Elstrodt J;Hoekstra HJ
目的.高温离体肢体灌注的可行性 （HILP）联合肿瘤坏死因子-α（TNF α）和顺铂治疗 在犬模型中研究骨肉瘤。 方法.在6只健康杂种犬的7次灌注期间 （体重32 ± 2 kg）在轻度高温（39 - 40 ℃）下HILP的技术方面， 研究了在5个实验中，HILP仅用TNF α（0.5 mg/l肢体体积）进行， 在两个实验中，TNF α与顺铂（25 mg/l肢体体积）联合使用。 在灌注过程中，监测生理参数， 测定顺铂浓度。 结果灌注条件（pH、PCO2、PO2、流量和压力） 三只狗在24小时内死亡，尽管亚致死 从灌注回路泄漏的TNF α的全身浓度。三只狗 终止;根据荷兰道德规则，第二次实验后一只狗; 一只狗表现出小肠内陷导致肠梗阻;一只狗，因为 灌注肢体的坏死。 结论.这项在健康犬中进行的可行性研究表明， HILP联合TNF α和顺铂与高死亡率相关， 我们用TNF α和顺铂HILP治疗自发性骨肉瘤犬。因此，我们认为， 在寻找灌注的理想组合时，应使用替代模型 用于人类骨肉瘤保肢治疗的药物。
Purpose. The feasibility of hyperthermic isolated limb perfusion (HILP) with tumor necrosis factor-α (TNFα ) and cisplatin for the management of osteosarcoma was studied in the canine model. Methods. During seven perfusions in six healthy mongrel dogs (weight 32±2 kg) technical aspects of HILP under mild hyperthermia (39– 40℃) were studied. In five experiments HILP was performed with TNFα alone (0.5 mg/l extremity volume), and in two experiments TNFα was combined with cisplatin (25 mg/l extremity volume). During the perfusions physiological parameters were monitored and TNFα and total cisplatin concentrations were determined. Results. Perfusion conditions (pH, PCO2 , PO2, flow and pressure) remained within physiological ranges.Three dogs died within 24 h despite a sublethal systemic concentration of TNFα that leaked from the perfusion circuit. Three dogs were terminated; one dog after the second experiment in accordance with Dutch ethical rules; one dog showed an invagination of the small bowel resulting in an ileus; one dog because of necrosis of the perfused limb. Conclusions. This feasibility study in healthy dogs demonstrated that HILP with TNFα and cisplatin was associated with a high mortality rate and does not allow us to treat dogs with spontaneous osteosarcoma with TNFα and cisplatin HILP. Therefore, an alternative model should be used in the search for the ideal combination of perfusion agents for limb sparing treatment in human osteosarcoma.