title: Radiofrequency ablation of colorectal liver metastases induces an inflammatory response in distant hepatic metastases but not in local accelerated outgrowth.
abstract: BACKGROUND
  Recently, we have shown in a murine model that radiofrequency ablation (RFA) induces accelerated outgrowth of colorectal micrometastases in the transition zone (TZ) surrounding the ablated lesion. Conversely, RFA also induces an anti-tumor T-cell response that may limit tumor growth at distant sites. Here we have evaluated whether an altered density of inflammatory cells could be observed in the perinecrotic (TZ) metastases compared to hepatic metastases in the distant reference zone (RZ).
  
  
  METHODS
  RFA-treated tumor-bearing mice (n = 10) were sacrificed. The inflammatory cell density (neutrophils, macrophages, CD4(+) T-cells, and CD8(+) T-cells) of tumors in the TZ (TZ tumors) was compared to that in tumors in the RZ (RZ tumors). Sham-operated, tumor-bearing mice (n = 10) were analyzed simultaneously as controls (sham-treated tumors).
  
  
  RESULTS
  In RFA-treated, tumor-bearing mice RZ tumors contained a significantly higher density of neutrophils and CD4(+) T-cells, but not macrophages and CD8(+) T-cells compared to sham-treated tumors. Notably, TZ tumors had a significantly lower density of neutrophils, CD4(+) T-cells, and CD8(+) T-cells, but not macrophages, when compared to RZ tumors.
  
  
  CONCLUSIONS
  The accelerated perinecrotic tumor outgrowth following RFA is associated with a reduced density of neutrophils and T-cells compared to distant hepatic metastases. This may have implications for local tumor recurrence following RFA.
authors.affiliation: Department of Surgery, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Maarten W
authors.initials: MW
authors.lastname: Nijkamp
authors.forename: Alie
authors.initials: A
authors.lastname: Borren
authors.forename: Klaas M
authors.initials: KM
authors.lastname: Govaert
authors.forename: Frederik J H
authors.initials: FJ
authors.lastname: Hoogwater
authors.forename: I Quintus
authors.initials: IQ
authors.lastname: Molenaar
authors.forename: Paul J
authors.initials: PJ
authors.lastname: van Diest
authors.forename: Onno
authors.initials: O
authors.lastname: Kranenburg
authors.forename: Inne H M
authors.initials: IH
authors.lastname: Borel Rinkes
mesh_terms: D000818:Animals; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D017115:Catheter Ablation / Q000009:adverse effects*; D015179:Colorectal Neoplasms / Q000473:pathology*; D007249:Inflammation / Q000209:etiology* / Q000473:pathology; D008113:Liver Neoplasms / Q000473:pathology* / Q000556:secondary / Q000628:therapy*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009364:Neoplasm Recurrence, Local / Q000473:pathology*; D009504:Neutrophils / Q000378:metabolism