title: Isolated hypoxic hepatic perfusion with retrograde outflow in patients with irresectable liver metastases; a new simplified technique in isolated hepatic perfusion.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Surgical Oncology, Erasmus University Medical Centre-Daniel den Hoed Cancer Centre, PO Box 5201, 3008 AE, Rotterdam, The Netherlands. c.verhoef@erasmusmc.nl
authors.forename: Cornelis
authors.initials: C
authors.lastname: Verhoef
authors.forename: Johannes H W
authors.initials: JH
authors.lastname: de Wilt
authors.forename: Flavia
authors.initials: F
authors.lastname: Brunstein
authors.forename: Andreas W K S
authors.initials: AW
authors.lastname: Marinelli
authors.forename: Boudewijn
authors.initials: B
authors.lastname: van Etten
authors.forename: Maarten
authors.initials: M
authors.lastname: Vermaas
authors.forename: Gunther
authors.initials: G
authors.lastname: Guetens
authors.forename: Gert
authors.initials: G
authors.lastname: de Boeck
authors.forename: Ernst A
authors.initials: EA
authors.lastname: de Bruijn
authors.forename: Alexander M M
authors.initials: AM
authors.lastname: Eggermont
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000379:methods*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D018450:Disease Progression; D005134:Eye Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D008401:Gas Chromatography-Mass Spectrometry; D006499:Hepatic Artery / Q000187:drug effects; D006801:Humans; D007261:Infusions, Intra-Arterial; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary* / Q000601:surgery; D008297:Male; D008558:Melphalan / Q000627:therapeutic use*; D008875:Middle Aged; D009382:Neoplasms, Unknown Primary / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D011169:Portal Vein / Q000187:drug effects; D012509:Sarcoma / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D008558:Melphalan