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document
Cytokine levels and systemic toxicity in patients undergoing isolated limb perfusion with high-dose tumor necrosis factor , interferon gamma , and melphalan . PURPOSE Isolated limb perfusion ( ILP ) with tumor necrosis factor ( TNF ) , interferon gamma , and melphalan ( M ) has been reported to result in high response rates for extremity melanoma and sarcoma . We have evaluated the relationship of systemic TNF exposure to induction of several secondary mediators and incidence of systemic toxicity . PATIENTS AND METHODS Nineteen patients with extremity melanoma ( n = 16 ) or sarcoma ( n = 3 ) , underwent 90-minute ILP with TNF-alpha , interferon gamma ( 0.2 mg ) , and M ( 10 to 13 mg/L of limb volume ) ( TNF/IFN/M ) ( n = 12 ) , or M alone ( n = 7 ) . Continuous intraoperative monitoring ( CIM ) for systemic leak from the perfusion circuit was performed using radioactive iodine-131 albumin . Cytokine levels in the perfusate and systemic circulation during and after ILP were measured by enzyme-linked immunosorbent assay . RESULTS Systemic leaks > or = 1 % from the perfusion circuit occurred in six patients who received TNF/IFN/M and in four who received M alone . Hypotension that required vasopressor support occurred in six of six patients with evidence of a leak ( > or = 1 % ) and zero of six patients without a leak ( < 1 % ) . These six patients had significantly higher peak systemic TNF levels during and after perfusion than patients without a leak ( 2.8 and 8.2 ng/mL v 0.7 and 2.0 ng/mL , respectively ; P < .05 ) . All patients who received TNF/IFN/M had significantly greater increases in systemic interleukin-6 ( IL-6 ) levels than in patients with M alone ( 12,395 +/- 10,374 pg/mL v 79.4 +/- 7.2 pg/mL , respectively ; P < .001 ) . Intracellular adhesion molecule ( ICAM ) , IL-8 , and TNF-R levels were also increased after ILP with TNF/IFN/M . CONCLUSION ILP with TNF/IFN/M can be safely performed , as I131 albumin provides a sensitive measure of systemic leakage from the perfusion circuit . Patients with a measured leak of > or = 1 % develop mild and transient postoperative hypotension with significantly higher systemic TNF levels and lower perfusate TNF levels than in patients without leaks .
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Intervention_Physical
isolated limb perfusion
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Intervention_Pharmacological
with high-dose tumor necrosis factor
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Intervention_Pharmacological
interferon gamma
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Intervention_Pharmacological
melphalan
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Intervention_Physical
Isolated limb perfusion ( ILP )
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Intervention_Pharmacological
with tumor necrosis factor ( TNF )
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Intervention_Pharmacological
interferon gamma
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Intervention_Pharmacological
melphalan ( M )
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Intervention_Physical
ILP
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Intervention_Pharmacological
with TNF-alpha
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Intervention_Pharmacological
interferon gamma
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Intervention_Pharmacological
M
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Intervention_Pharmacological
TNF/IFN/M
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Intervention_Control
M alone
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Intervention_Pharmacological
iodine-131 albumin
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Outcome_Physical
Cytokine levels
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Outcome_Adverse-effects
systemic toxicity
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Outcome_Other
response rates
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Outcome_Physical
secondary mediators
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Outcome_Adverse-effects
systemic toxicity
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Outcome_Adverse-effects
Systemic leaks
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Outcome_Physical
> or = 1 %
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Outcome_Physical
perfusion circuit
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Outcome_Adverse-effects
Hypotension that required vasopressor support
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Outcome_Physical
peak systemic TNF levels
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Outcome_Physical
systemic interleukin-6 ( IL-6 ) levels
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Outcome_Physical
Intracellular adhesion molecule ( ICAM ) , IL-8 , and TNF-R levels
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Participant_Condition
undergoing isolated limb perfusion with high-dose tumor necrosis factor , interferon gamma , and melphalan
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Participant_Sample-size
Nineteen
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Participant_Condition
extremity melanoma
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Participant_Condition
sarcoma