title: TNF-alpha and melphalan-based isolated limb perfusion: no evidence supporting the early destruction of tumour vasculature.
abstract: BACKGROUND
  Isolated limb perfusion with TNF-alpha and melphalan (TM-ILP) is a highly effective treatment for locally advanced tumours of the extremities. Previous research suggests an almost immediate disintegration of the blood supply of the tumour. The aim of the present study was to verify this hypothesis using non-invasive measurements of microvascular perfusion and tissue oxygenation.
  
  
  METHODS
  A total of 11 patients were included in the study. TM-ILP was performed under mildly hyperthermic conditions (39 °C) in the extremities via proximal vascular access. Capillary-venous microvascular blood flow, haemoglobin level (Hb) and oxygen saturation (SO2) were determined using laser Doppler and white-light spectroscopy, respectively, before TM-ILP and at 30 min, 4 h, 1 day, 4 days, 1 week, 2 weeks and 6 weeks after TM-ILP from tumour and healthy muscle tissues.
  
  
  RESULTS
  Blood flow and Hb were mostly higher, whereas SO2 was lower, in tumour tissue compared with muscle tissue. In both tumour and muscle tissues, blood flow significantly increased immediately after TM-ILP and remained elevated for at least 2 weeks, followed by a return to the initial values 6 weeks after the procedure.
  
  
  CONCLUSIONS
  No signs were found of early destruction of the tumour vasculature. The observations suggest that an inflammatory reaction is one of the key elements of TM-ILP.
authors.affiliation: Section for Sarcoma Surgery, Department of General, Visceral and Transplantation Surgery, University Hospital of Essen and Sarcoma Center at the West German Cancer Center (WTZ), University of Duisburg-Essen, Hufelandstrasse 55, D-45122 Essen, Germany.
authors.forename: L E
authors.initials: LE
authors.lastname: Podleska
authors.affiliation: Institut für Physiologische Chemie, Universitätsklinikum Essen, Hufelandstrasse 55, D-45122 Essen, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Funk
authors.affiliation: Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital of Essen and Sarcoma Center at the West German Cancer Center (WTZ), University of Duisburg-Essen, Hufelandstrasse 55, D-45122 Essen, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Umutlu
authors.affiliation: Zentrum fuer Pathologie Essen-Mitte, ZPEM, Am Deimelsberg 34a, D-45276 Essen, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Grabellus
authors.affiliation: Section for Sarcoma Surgery, Department of General, Visceral and Transplantation Surgery, University Hospital of Essen and Sarcoma Center at the West German Cancer Center (WTZ), University of Duisburg-Essen, Hufelandstrasse 55, D-45122 Essen, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Taeger
authors.affiliation: Institut für Physiologische Chemie, Universitätsklinikum Essen, Hufelandstrasse 55, D-45122 Essen, Germany.
authors.forename: H
authors.initials: H
authors.lastname: de Groot
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000379:methods; D005121:Extremities / Q000473:pathology*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology; D010100:Oxygen / Q000378:metabolism; D012039:Regional Blood Flow / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage
chemical_list: D018906:Antineoplastic Agents, Alkylating; D006454:Hemoglobins; D014409:Tumor Necrosis Factor-alpha; D008558:Melphalan; D010100:Oxygen