[Hyperthermic isolated limb perfusion with TNF-alpha and melphalan for the treatment of locally advanced soft-tissue sarcoma].

[OBJECTIVE] Regional neoadjuvant isolated limb perfusion (ILP) with TNF-alpha and melphalan (TM-ILP) for the treatment of primarily unresectable highly malignant soft tissue sarcomas. The goal is to reduce the size and devitalize the tumor in order to convert a primarily unresectable tumor into a resectable state.

[INDICATIONS] Primarily nonresectable (indication for amputation or higher-grade mutilating resection), highly malignant soft tissue sarcomas of the extremities.

[CONTRAINDICATIONS] Vascular occlusions, thromboses, acute infections, especially of the affected extremity.

[SURGICAL TECHNIQUE] Vascular access to the artery and vein proximal to the affected limb. Arterial and venous cannulation of the vessels supplying the limb and tumor. Connection to a heart-lung machine. Application of a tourniquet or elastic bandage proximal to the catheter tips. Nuclear medicine leak rate measurement (technetium 99m) to rule out a systemic leak. Perfusion of the limb with 1-2 mg recombinant TNF-alpha (Tasonermin/Beromun, Belpharma SA, Luxembourg) for 15 min, followed by the addition of 11-13 mg melphalan per liter of limb volume and subsequent perfusion for an additional 60 min. Washing out with 2-5 l of crystalloid solution while wrapping the limb several times with elastic Esmarch bandages. Removal of the tourniquet and catheters, reconstruction of the vessels, wound closure.

[POSTOPERATIVE MANAGEMENT] Elevate and cool the limb (especially the forearm and lower leg). Close cardiovascular and clinical monitoring for existing risk of TNF-alpha-induced Septic Inflammatory Response Syndrome (SIRS) and compartment syndrome (occurring within the first 24 h after ILP). Full weight-bearing on the limb is possible. Continue elevated positioning therapy depending on the degree of swelling. The hospital stay is approximately 1 week.

[RESULTS] Overall treatment response to TM-ILP: 60-70%. Complete remissions observed in just under 20% of cases. Limb preservation is possible in over 80% of cases.