Isolated Hypoxic Hepatic Perfusion with Retrograde Outflow in Patients with Irresectable Liver Metastases; A New Simplified Technique in Isolated Hepatic Perfusion

• Published in: Annals of surgical oncology Vol. 15; no. 5; pp. 1367 - 1374
• Main Authors: Verhoef, Cornelis, de Wilt, Johannes H. W., Brunstein, Flavia, Marinelli, Andreas W. K. S., van Etten, Boudewijn, Vermaas, Maarten, Guetens, Gunther, de Boeck, Gert, de Bruijn, Ernst A., Eggermont, Alexander M. M.
• Format: Journal Article
• Language: English
• Published: New York Springer-Verlag 01.05.2008; Springer Nature B.V
• Subjects: Adult; Aged; Antineoplastic Agents, Alkylating - therapeutic use; Chemotherapy, Cancer, Regional Perfusion - methods; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - pathology; Colorectal Neoplasms - surgery; Disease Progression; Eye Neoplasms - drug therapy; Eye Neoplasms - pathology; Eye Neoplasms - surgery; Female; Follow-Up Studies; Gas Chromatography-Mass Spectrometry; Hepatic and Pancreatic Tumors; Hepatic Artery - drug effects; Humans; Infusions, Intra-Arterial; Liver Neoplasms - drug therapy; Liver Neoplasms - secondary; Liver Neoplasms - surgery; Male; Medicine; Medicine & Public Health; Melphalan - therapeutic use; Middle Aged; Neoplasms, Unknown Primary - drug therapy; Neoplasms, Unknown Primary - pathology; Neoplasms, Unknown Primary - surgery; Oncology; Portal Vein - drug effects; Sarcoma - drug therapy; Sarcoma - pathology; Sarcoma - surgery; Surgery; Surgical Oncology; Survival Rate; Treatment Outcome; Retrograde outflow; Isolated hepatic perfusion; Hypoxic; Metastasis; Melphalan
• ISSN: 1068-9265; 1534-4681
• DOI: 10.1245/s10434-007-9714-z

Background Isolated hepatic perfusion with high-dose chemotherapy is a treatment option for patients with irresectable metastases confined to the liver. Prolonged local control and impact on survival have been claimed. Major drawbacks are magnitude and costs of the procedure. We developed an isolated hypoxic hepatic perfusion (IHHP) with retrograde outflow without the need for a heart-lung machine. Patients and Methods Twenty-four consecutive patients with irresectable metastases of various origins were treated. IHHP inflow was via the hepatic artery, outflow via the portal vein with occlusion of the retrohepatic caval vein. Radiolabeled albumine was used for leakage monitoring. Melphalan was used at 1–2 mg/kg. A 25-minute perfusion period was followed by a complete washout. Local and systemic melphalan concentrations were determined. Results Compared with oxygenated classical IHP, the IHPP procedure reduced operation time from >8 h to 4 hours, blood loss from >4000 to 900 cc and saved material and personnel costs. Leakage was 0% with negligible systemic toxicity and 0% perioperative mortality. Tumor response: complete response (CR) in 4%, partial response (PR) in 58%, and stable disease (SD) in 13%. Median time to progression was 9 months (2–24 months); pharmacokinetics demonstrated intrahepatic melphalan concentrations more than 9 fold higher than postperfusion systemic concentrations. Conclusions IHPP is a relatively simple procedure with reduced costs, reduced blood loss, no mortality, limited toxicity, and response rates comparable to classic IHP. The median duration of 9 months of tumor control should be improved. Hereto, vasoactive drugs, will be explored in further studies.