Hyperthermic Isolated Limb Perfusion with TNFαand Cisplatin in theTreatment of Osteosarcoma of the Extremities: A Feasibility Study inHealthy Dogs

[摘要] Purpose.The feasibility of hyperthermic isolated limb perfusion(HILP) with tumor necrosis factor-α (TNFα ) and cisplatin for the management ofosteosarcoma 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℃) werestudied. 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 totalcisplatin concentrations were determined.Results.Perfusion conditions (pH,PCO2,PO2, flow and pressure)remained within physiological ranges.Three dogs died within 24 h despite a sublethalsystemic concentration of TNFα that leaked from the perfusion circuit. Three dogs wereterminated; 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 becauseof necrosis of the perfused limb.Conclusions.This feasibility study in healthy dogs demonstrated thatHILP with TNFα and cisplatin was associated with a high mortality rate and does not allowus 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 perfusionagents for limb sparing treatment in human osteosarcoma.

[学科分类] 肿瘤学