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

Steven K. Libutti, David L. Bartlett, Douglas L. Fraker, H. Richard Alexander

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Background: For a variety of histologies, the liver represents the only or the dominant site of metastatic disease. Regional treatment of the liver has the theoretic advantage of maximizing drug delivery while minimizing systemic toxicity. This article describes the technique of isolated hepatic perfusion using tumor necrosis factor and melphalan under conditions of moderate hyperthermia for the treatment of unresectable liver tumors. Study Design: Fifty patients with biopsy-proved unresectable primary or metastatic cancer to the liver were treated. Isolated hepatic perfusion was performed for 60 minutes under conditions of moderate hyperthermia during a laparotomy with inflow through the gastroduodenal artery and outflow through an isolated segment of inferior vena cava. During isolated hepatic perfusion portal and infrahepatic blood flow were shunted externally by a centrifugal pump to the axillary vein. Complete vascular isolation was confirmed intraoperatively using a continuous 131I-labeled serum albumin leak monitoring system. Operative and perfusion parameters were recorded. Results: By using a standard operative technique to achieve complete vascular isolation of the liver during perfusion, there was no leak of perfusate detected in 48 of 50 patients as determined by the continuous leak monitoring system and absence of detectable-systemic tumor necrosis factor levels. Operating time, transfusion requirements, and blood loss were within the range expected for a major operative procedure. Stable hemodynamic and perfusion parameters were achieved consistently and all patients successfully completed the 60-minute perfusion. Two patients (4%) died as a result of treatment 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 without systemic exposure. By using a standard operative technique, continuous intraoperative leak monitoring, and an external veno-veno bypass circuit, this 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 better define the role of isolated hepatic perfusion in the treatment of unresectable liver tumors. (C) 2000 by the American College of Surgeons.

Original languageEnglish (US)
Pages (from-to)519-530
Number of pages12
JournalJournal of the American College of Surgeons
Volume191
Issue number5
DOIs
StatePublished - 2000
Externally publishedYes

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Melphalan
Tumor Necrosis Factor-alpha
Perfusion
Liver
Neoplasms
Therapeutics
Blood Vessels
Fever
Axillary Vein
Intraoperative Monitoring
Biological Therapy
Operative Surgical Procedures
Inferior Vena Cava
Liver Neoplasms
Serum Albumin
Blood Transfusion
Laparotomy
Histology
Arteries
Hemodynamics

ASJC Scopus subject areas

  • Surgery

Cite this

Technique and results of hyperthermic isolated hepatic perfusion with tumor necrosis factor and melphalan for the treatment of unresectable hepatic malignancies. / Libutti, Steven K.; Bartlett, David L.; Fraker, Douglas L.; Alexander, H. Richard.

In: Journal of the American College of Surgeons, Vol. 191, No. 5, 2000, p. 519-530.

Research output: Contribution to journalArticle

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abstract = "Background: For a variety of histologies, the liver represents the only or the dominant site of metastatic disease. Regional treatment of the liver has the theoretic advantage of maximizing drug delivery while minimizing systemic toxicity. This article describes the technique of isolated hepatic perfusion using tumor necrosis factor and melphalan under conditions of moderate hyperthermia for the treatment of unresectable liver tumors. Study Design: Fifty patients with biopsy-proved unresectable primary or metastatic cancer to the liver were treated. Isolated hepatic perfusion was performed for 60 minutes under conditions of moderate hyperthermia during a laparotomy with inflow through the gastroduodenal artery and outflow through an isolated segment of inferior vena cava. During isolated hepatic perfusion portal and infrahepatic blood flow were shunted externally by a centrifugal pump to the axillary vein. Complete vascular isolation was confirmed intraoperatively using a continuous 131I-labeled serum albumin leak monitoring system. Operative and perfusion parameters were recorded. Results: By using a standard operative technique to achieve complete vascular isolation of the liver during perfusion, there was no leak of perfusate detected in 48 of 50 patients as determined by the continuous leak monitoring system and absence of detectable-systemic tumor necrosis factor levels. Operating time, transfusion requirements, and blood loss were within the range expected for a major operative procedure. Stable hemodynamic and perfusion parameters were achieved consistently and all patients successfully completed the 60-minute perfusion. Two patients (4{\%}) died as a result of treatment 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 without systemic exposure. By using a standard operative technique, continuous intraoperative leak monitoring, and an external veno-veno bypass circuit, this 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 better define the role of isolated hepatic perfusion in the treatment of unresectable liver tumors. (C) 2000 by the American College of Surgeons.",
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