title: Radio-frequency ablation of hepatocellular carcinoma before liver transplantation: a histologic and 'TUNEL' study.
abstract: BACKGROUND
  Radio-frequency ablation (RFA) is an increasingly used treatment modality for hepatocellular carcinoma (HCC) in patients awaiting liver transplantation (OLTX). The current study evaluates the effectiveness of RFA in this setting based on evaluation of total cell death in explanted native livers.
  
  
  METHODS
  We evaluated 36 tumors from 35 patients with RFA-treated HCC who underwent OLTX at our center between 1998 and 2002. Native livers from OLTX were extensively sampled for histologic evaluation. For each HCC, an estimate ratio of necrotic tumor areas was calculated based on hematoxylin and eosin (H&E) sections. In tumors with 10% or more residual viable areas, Tdt-mediated UTP nick-end labeling (TUNEL) was further performed to assess apoptosis in the morphologically 'viable' areas. A final 'tumor cell death' (TCD) ratio was recalculated for each HCC to include areas of apoptosis identified by TUNEL.
  
  
  RESULTS
  Based on H&E evaluation, 22/36 (61.1%) HCC revealed > or = 90% necrosis including 12/36 HCC (33.3%) showing no evidence of residual viable tumor. The overall median tumor necrosis was 79%. When TUNEL findings were added, 26/36 (72.2%) HCC revealed > or = 90% TCD including 14/36 HCC (38.8%) showing complete TCD (median TCD of 88.4%). None of our patients died of HCC while awaiting OLTX. Longer RFA-to-transplant time appears to be associated with a higher TCD rate (median of 154.5 days in patients with less than 90% TCD vs 326 days for patients with > or = 90% TCD; P = 0.019). There was no significant correlation between tumor grade or pre-RFA size of the tumors and TCD rate in RFA-treated HCC (P = 0.11).
  
  
  CONCLUSIONS
  Extensive TCD (88.4% median) can be obtained using RFA for HCC in patients awaiting OLTX. Our TUNEL findings suggest that RFA-induced cell injury could be associated with apoptosis.
authors.affiliation: Department of Pathology, Baylor University Medical Center, Dallas, TX, USA. gnetto1@jhmi.edu
authors.forename: G J
authors.initials: GJ
authors.lastname: Netto
authors.forename: B
authors.initials: B
authors.lastname: Altrabulsi
authors.forename: N
authors.initials: N
authors.lastname: Katabi
authors.forename: P
authors.initials: P
authors.lastname: Martin
authors.forename: K
authors.initials: K
authors.lastname: Burt
authors.forename: M
authors.initials: M
authors.lastname: Levy
authors.forename: E
authors.initials: E
authors.lastname: Sanchez
authors.forename: D L
authors.initials: DL
authors.lastname: Watkins
authors.forename: L
authors.initials: L
authors.lastname: Jennings
authors.forename: G
authors.initials: G
authors.lastname: Klintmalm
authors.forename: R
authors.initials: R
authors.lastname: Goldstein
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D015331:Cohort Studies; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D008113:Liver Neoplasms / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D011446:Prospective Studies; D000078702:Radiofrequency Therapy