Hyperthermic Isolated Limb Perfusion for Melanoma

Abstract

In-transit melanoma metastases arise from lymphatic spread and growth in relative proximity to the primary melanoma. When confined to an extremity, in-transit metastases are effectively treated with hyperthermic isolated limb perfusion. The technique, first described in the 1950s, involves an operation to place cannulas into the main source artery and draining vein of the extremity, with connection to a heart-lung bypass machine. When a tourniquet is applied to the extremity, isolated perfusion is achieved, and the circuit can also be warmed (hyperthermia). Specific details of the operative dissection, fluid and blood pressure management, patient positioning, and pump flow rates are important to minimize leakage between the isolated circuit and systemic circulation. The primary drug used to date is melphalan, which is taken up by the tissue rapidly and causes DNA damage by formation of cross-bridges. Several different regimens of drug dose, perfusion duration, and treatment temperature remain in use today; there is no uniformly agreed-upon treatment schedule. Published rates of response range from 60% to 90%, with complete responses observed in 25–66% of cases. Toxicities and complications of management include lymphedema, skin blistering, painful neuralgia, myopathy, and neutropenia. The frequency with which hyperthermic isolated limb perfusion is used for melanoma in-transit metastases in recent years has declined in favor of systemic therapies, which have become more effective. Nonetheless, hyperthermic isolated limb perfusion remains very effective and useful in selected patients.