Technique and results of hyperthermic isolated hepatic perfusion with tumor necrosis factor and melphalan for the treatment of unresectable hepatic malignancies

Background: For a variety of histologies, the liver represents the only or the dominant site of metastatic disease. Regional treatment of the liver ha s the theoretic advantage of maximizing drug delivery while minimizing syst emic toxicity. This article describes the technique of isolated hepatic per fusion using tumor necrosis factor and melphalan under conditions of modera te hyperthermia for the treatment of unresectable liver tumors. Study Design: Fifty patients with biopsy-proved unresectable primary or met astatic cancer to the liver were treated. Isolated hepatic perfusion was pe rformed for 60 minutes under conditions of moderate hyperthermia during a l aparotomy with inflow through the gastroduodenal artery and outflow through an isolated segment of inferior vena cava. During isolated hepatic perfusi on portal and infrahepatic blood flow were shunted externally by a centrifu gal pump to the axillary vein. Complete vascular isolation was confirmed in traoperatively using a continuous I-131-labeled serum albumin leak monitori ng system. Operative and perfusion parameters were recorded. Results: By using a standard operative technique to achieve complete vascul ar isolation of the liver during perfusion, there was no leak of perfusate detected in 48 of 50 patients as determined by the continuous leak monitori ng system and absence of detectable systemic tumor necrosis factor levels. Operating time, transfusion requirements, and blood loss were within the ra nge expected for a major operative procedure. Stable hemodynamic and perfus ion parameters were achieved consistently and all patients successfully com pleted the 60-minute perfusion. Two patients (4%) died as a result of treat ment and significant tumor regression was observed in 75%. Conclusions: Isolated hepatic perfusion is a technique that can be used to deliver high doses of chemotherapy or biologic therapy regionally and witho ut systemic exposure. By using a standard operative technique, continuous i ntraoperative leak monitoring, and an external veno-veno bypass circuit, th is procedure can be done safely and with acceptable morbidity and mortality . This article demonstrates that sustained and complete vascular isolation of the liver can be achieved and indicates further study is warranted to be tter define the role of isolated hepatic perfusion in the treatment of unre sectable liver tumors. (J Am Coll Surg 2000;191: 519-530. (C) 2000 by the A merican College of Surgeons).