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• W2146604966 abstract "<h3>Background:</h3> The tolerated systemic dose of recombinant tumor necrosis factor α (rTNF-α) is very limited, since its administration leads to a severe septic shock—like condition. Its implementation in isolated limb perfusion (ILP) for metastatic melanoma or advanced soft-tissue sarcoma confined to the limb facilitates doses of rTNF-α 10 times higher than the systemic tolerated dose. However, with the traditional high flow rate used in ILP, systemic leakage and side effects are not eliminated. <h3>Objective:</h3> To determine if a lower perfusion flow rate would reduce leakage and consequently toxic effects. <h3>Methods:</h3> Isolated limb perfusion was performed for melanoma and soft-tissue sarcoma confined to the limb using a flow rate of 869 ±122 mL/min in nine patients (group 1) and a lower rate of 286±62 mL/min in six patients (group 2). <h3>Results:</h3> The systemic leakage rate was 12.5%±2.9% in group 1, compared with 2.3%±1.0% in group 2 (<i>P</i>=.003). Peak TNF-α levels were 29 000±2700 pg/mL in group 1, higher than 1580±1355 pg/mL in group 2 (<i>P</i>=.02). The tachycardia, hypotension, increased cardiac output, decreased systemic vascular resistance, bilirubinemia, elevation of liver enzyme levels, hypocholestrolemia, thrombocytopenia, and prolongation of prothrombin and partial thromboplastin times all observed in group 1 were significantly attenuated or eliminated in group 2. The limb Po₂, Pco₂, pH, and viability remained similar in both groups. Also, the tumor response rate remained high and was unaffected by the decrease in flow rate. <h3>Conclusions:</h3> Decreasing perfusion flow rate during ILP results in diminished leakage of TNF-α Consequently, the systemic hemodynamic, metabolic, and hematologic toxic effects are virtually abolished. (Arch Surg. 1995;130:1079-1084)" @default.
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• W2146604966 date "1995-10-01" @default.
• W2146604966 modified "2023-09-29" @default.
• W2146604966 title "Systemic Leakage and Side Effects of Tumor Necrosis Factor α Administered Via Isolated Limb Perfusion Can Be Manipulated by Flow Rate Adjustment" @default.
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• W2146604966 doi "https://doi.org/10.1001/archsurg.1995.01430100057012" @default.
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