title: Evidence for tumor cell spread during local hepatic ablation of colorectal liver metastases.
abstract: BACKGROUND
  The aim of the present study was to analyze the impact of cryosurgery (CRYO) on liver metastases compared to other thermoablative techniques. In a rat liver metastases model, evidence for tumor cell spread was analyzed comparing CRYO, radiofrequency ablation (RFA), and laser-induced thermotherapy (LITT).
  
  
  METHODS
  In an experimental study, we compared cell spillage in the washout of isolated perfused rat livers undergoing thermal ablation. Within the same model, CC531-GFP rat liver tumors were treated with CRYO, RFA, or LITT and the number of vital tumor cells within the perfusate was measured. Matrix metalloproteinases (MMP-2, MMP-9) were analyzed after in vivo ablation of rat colorectal liver metastases in the third experimental model.
  
  
  RESULTS
  Our data showed pronounced washout of cells after CRYO with a higher amount of intravascular cells and cell detritus compared to RFA and LITT. Only the effluent fluid of cryosurgery-treated livers revealed GFP-stained tumor cells. MMP-2 and MMP-9 expression was significantly higher after cryosurgery than after RFA and LITT.
  
  
  CONCLUSIONS
  When using thermoablative techniques, intravascular metastatic cell spillage is highest in CRYO, and increased expression of matrix metalloproteinases may further facilitate tumor cell spread. Therefore, RFA and LITT may be preferable whenever surgical resection of liver tumors is impossible.
authors.affiliation: Department of General, Visceral, Vascular and Pediatric Surgery, University of Saarland, Homburg/Saar, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Schuld
authors.forename: Sven
authors.initials: S
authors.lastname: Richter
authors.forename: Ludwig W W
authors.initials: LW
authors.lastname: Oberkircher
authors.forename: Ute
authors.initials: U
authors.lastname: Seeland
authors.forename: Katharina I
authors.initials: KI
authors.lastname: Debnar-Daumler
authors.forename: Jana
authors.initials: J
authors.lastname: Rauch
authors.forename: Michael D
authors.initials: MD
authors.lastname: Menger
authors.forename: Martin K
authors.initials: MK
authors.lastname: Schilling
authors.forename: Otto
authors.initials: O
authors.lastname: Kollmar
mesh_terms: D000818:Animals; D001826:Body Fluids / Q000166:cytology / Q000378:metabolism; D017115:Catheter Ablation / Q000009:adverse effects / Q000379:methods; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D003452:Cryosurgery / Q000009:adverse effects / Q000379:methods; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D006498:Hepatectomy / Q000009:adverse effects* / Q000379:methods*; D006979:Hyperthermia, Induced / Q000009:adverse effects / Q000379:methods; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary* / Q000601:surgery*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009368:Neoplasm Transplantation; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D049452:Green Fluorescent Proteins; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat