title: Radiofrequency Ablation of Hepatocellular Carcinoma with a "Nodule-in-Nodule" Appearance: Long-Term Follow-up and Clinical Implications.
abstract: OBJECTIVE
  Hepatocellular carcinoma (HCC) with a "nodule-in-nodule" (NIN) appearance has unique histological characteristics as an early HCC. We assessed long-term therapeutic outcomes of radiofrequency ablation (RFA) in HCC patients considering this appearance.
  
  
  METHODS
  Our Institutional Review Board approved this retrospective study, and the requirement for written informed consent was waived. Between May 2006 and April 2012, a total of 572 patients underwent RFA for single HCC as a first-line treatment. Patients were divided into a NIN HCC group (n = 22) and a non-NIN HCC group (n = 550), according to the NIN feature on pretreatment imaging studies. Local tumor progression (LTP) and disease-free survival (DFS) were compared. Prognostic factors for LTP and DFS were assessed using a Cox proportional hazards model.
  
  
  RESULTS
  The cumulative LTP rates were 4.6 and 4.6% at 3 and 5 years, respectively, in the NIN HCC group, and 15.9 and 20.5% in the non-NIN HCC group, with borderline statistical significance (p = 0.085). The corresponding DFS rates were 53.8 and 37.7% in the NIN HCC group and 44.0 and 31.7% in the non-NIN HCC group, with no significant difference (p = 0.318). Although on multivariate analysis only tumor size was a significant prognostic factor for LTP, there was a trend bordering on the significance for the NIN feature [hazard ratio (HR) = 0.19; p = 0.099]. However, it was not a significant factor for DFS (HR = 0.18; p = 0.682).
  
  
  CONCLUSIONS
  The NIN appearance, a rare (4%, 22/550) but unique feature of early HCC, may be a favorable prognostic factor for RFA in terms of local tumor control.
authors.affiliation: Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-Dong, Gangnam-gu, Seoul, 135-710, Korea.
authors.forename: Tae Wook
authors.initials: TW
authors.lastname: Kang
authors.affiliation: Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-Dong, Gangnam-gu, Seoul, 135-710, Korea. rhimhc@skku.edu.
authors.forename: Hyunchul
authors.initials: H
authors.lastname: Rhim
authors.affiliation: Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-Dong, Gangnam-gu, Seoul, 135-710, Korea.
authors.forename: Kyoung Doo
authors.initials: KD
authors.lastname: Song
authors.affiliation: Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-Dong, Gangnam-gu, Seoul, 135-710, Korea.
authors.forename: Min Woo
authors.initials: MW
authors.lastname: Lee
authors.affiliation: Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-Dong, Gangnam-gu, Seoul, 135-710, Korea.
authors.forename: Dong Ik
authors.initials: DI
authors.lastname: Cha
authors.affiliation: Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-Dong, Gangnam-gu, Seoul, 135-710, Korea.
authors.forename: Sang Yun
authors.initials: SY
authors.lastname: Ha
authors.affiliation: Biostatics Team, Samsung Medical Center, Samsung Biomedical Research Institute, 50 Irwon-Dong, Gangnam-gu, Seoul, 135-710, Korea.
authors.forename: Joong Hyun
authors.initials: JH
authors.lastname: Ahn
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008099:Liver / Q000473:pathology / Q000601:surgery; D008113:Liver Neoplasms / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies
keywords: Complication; Hepatocellular carcinoma; Nodule-in-nodule; Radiofrequency ablation; Therapeutic outcome