title: Perineural invasion is a prognostic factor in intrahepatic cholangiocarcinoma.
abstract: BACKGROUND
  Perineural invasion is commonly observed in biliary tract cancer and is an independent prognostic factor. Since intrahepatic cholangiocarcinoma (ICC) develops from biliary epithelia in the liver, ICC may share the same characteristics in terms of the prognostic implications of perineural invasion. The aim of this study was to evaluate the clinical significance of perineural invasion in ICC.
  
  
  METHODS
  A total of 59 patients with ICC who underwent hepatectomy were retrospectively reviewed. The numbers of nerves with and without tumor involvement were counted. The perineural invasion index (PNI) was calculated as the number of involved nerves divided by the total number of nerves examined. Predictors for perineural invasion and prognostic factors were analyzed.
  
  
  RESULTS
  Perineural invasion was observed in 47 of 59 (80%) patients, and the median PNI was 0.082. The macroscopic tumor appearance and tumor location were significantly associated with perineural invasion (p = 0.013 and 0.032, respectively). Univariate and multivariate analyses (excluding seven in-hospital deaths) revealed that histologic grade, the presence of perineural invasion, nodal metastasis, and intrahepatic metastasis were independent prognostic factors. The survival rate of the patients with (n = 42) or without (n = 10) perineural invasion was 17 and 80% at 3 years; and 17 and 70% at 5 years, respectively (p = 0.001).
  
  
  CONCLUSIONS
  Perineural invasion is frequently found in patients with ICC and is an independent prognostic factor. ICC is an aggressive tumor similar to other biliary tract cancers. Because perineural invasion is a histologic marker of aggressiveness, it potentially has a role as a determinant of patient selection for adjuvant therapy.
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Shirai
authors.forename: Tomoki
authors.initials: T
authors.lastname: Ebata
authors.forename: Koji
authors.initials: K
authors.lastname: Oda
authors.forename: Hideki
authors.initials: H
authors.lastname: Nishio
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Nagasaka
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nimura
authors.forename: Masato
authors.initials: M
authors.lastname: Nagino
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D001653:Bile Ducts, Intrahepatic; D018281:Cholangiocarcinoma / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009412:Nerve Fibers / Q000473:pathology; D010525:Peripheral Nerves / Q000473:pathology; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome
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