A hazard of regional perfusion for melanoma is incomplete isolation, resulting in leakage of the cytostatic drug into the systemic circulation. Data were analysed retrospectively on 438 melphalan perfusions performed f o r melanoma of the extremities during the period [1978][1979][1980][1981][1982][1983][1984][1985][1986][1987][1988][1989][1990]; continuous isotopic measurement of systemic leakage was carried out. The cumulal'ive systemic leakage after 60 min perfusion was 0.9 per cent (95 per cent conjidence interval 0.7-1.1 per cent). Systemic leakage of 31 per cent was detected in 12.6 per cent of perfusions, 2 5 p e r cent in 6.2per cent and 2 10 per cent in 1.4per cent. In 2.3 per cent of patients, systemic side-eflects in the form of mild transient bone marrow depression occurred. Six variables related to the perfusion technique were assessed by multivariate analysis for their influence on systemic leakage. The level of isolation and diameter of the venous cannula emerg,ed as signiJicant factors. In addition, ligation of the internal iliac vein provided optimal isolation during iliac perfusion.
Regional isolated perfusion, introduced by Creech et a/. in 1958, is frequently used in the treatment of recurrent melanoma of the extremities'. Its main advantage is that a high dose of cytostatic drug (usually melphalan ) can be given locoregionally, thereby avoiding systemic side-effects3. However, complete isolation of the limb is not always possible because of anatomical variation and for technical reasons; systemic leakage therefore sometimes cannot be prevented. In most perfusion centres, control of systemic leakage is carried out using an isotope technique. In the literature, systemic leakage at the end of melphalan perfusion has been reported to be as high as 30 per cent, producing systemic complications (including bone marrow depression) in 2-17 per cent of Recently, biological response modifiers such as recombinant tumour necrosis factor (rTNF) x have become available for high-dose regional administration". Because the pharmacokinetic behaviour of these agents is different from that of melphalan and because their systemic toxicity can be severe, a proper isolation technique is even more crucial. Before embarking on perfusion with such agents, past experience of systemic leakage was evaluated. Particular attention was paid to six variables that might influence leakage.