title: Analysis of risk factors for recurrence after curative resection of well-differentiated pancreatic neuroendocrine tumors based on the new grading classification.
abstract: BACKGROUND
  It is difficult to predict the malignant potential of pancreatic neuroendocrine tumors (PNETs) precisely. This study investigated the validity of a new grading system adopted by the World Health Organization 2010 classification to determine risk factors for recurrence of PNETs.
  
  
  METHODS
  Data of 70 patients with PNETs who underwent curative resection were retrospectively examined by uni- and multivariate analyses. Histopathological findings were re-reviewed by experienced pathologists. NET G1 was defined as mitotic count <2 per 10 high power fields (HPF) and/or ≤2% Ki67 index, and NET G2 as 2-20 mitosis per 10 HPF and/or 3-20% Ki67 index.
  
  
  RESULTS
  There were 58 patients with NET G1 and 12 with NET G2. Incidence of recurrence was 11.4%. Univariate analysis demonstrated significant risk factors for recurrence including NET G2 of histological grade (P = 0.0089), male gender (P = 0.0333), tumor size ≥ 20 mm (P = 0.0117), lymph node metastasis (P = 0.0004), liver metastasis (P < 0.0001), lymphatic invasion (P = 0.046), and neural invasion (P = 0.0002). By multivariate analysis, histological grade (hazard ratio; 59.76, P = 0.0022) and neural invasion (hazard ratio; 147.49, P = 0.0016) were significantly associated with recurrence of PNETs.
  
  
  CONCLUSIONS
  This study confirmed the prognostic relevance of the new grading classification and that evaluation of perineural invasion and histological grade should be considered as prognostic predictors in well-differentiated PNETs (NET G1 and G2).
authors.affiliation: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Fukuoka, 812-8582, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Tsutsumi
authors.forename: Takao
authors.initials: T
authors.lastname: Ohtsuka
authors.forename: Minoru
authors.initials: M
authors.lastname: Fujino
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakashima
authors.forename: Shinichi
authors.initials: S
authors.lastname: Aishima
authors.forename: Junji
authors.initials: J
authors.lastname: Ueda
authors.forename: Shunichi
authors.initials: S
authors.lastname: Takahata
authors.forename: Masafumi
authors.initials: M
authors.lastname: Nakamura
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Oda
authors.forename: Masao
authors.initials: M
authors.lastname: Tanaka
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D015331:Cohort Studies; D016001:Confidence Intervals; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading / Q000145:classification*; D009361:Neoplasm Invasiveness / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology*; D018358:Neuroendocrine Tumors / Q000401:mortality / Q000473:pathology* / Q000601:surgery*; D010190:Pancreatic Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery*; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome; D014944:World Health Organization; D055815:Young Adult
keywords: Grading classification; Neural invasion; Pancreatic neuroendocrine tumor; Predictors of recurrence; WHO 2010 classification