title: Validation of the 2010 WHO classification and a new prognostic proposal: A single centre retrospective study of well-differentiated pancreatic neuroendocrine tumours.
abstract: BACKGROUND
  In 2010, the World Health Organization (WHO) modified the classification for pancreatic neuroendocrine tumours (NETs). Recently, some modifications were proposed to improve its prognostic value. The aim of this study was to test the prognostic value of both the original and the modified 2010 WHO grading systems.
  
  
  METHODS
  One hundred and twenty consecutive patients surgically resected for well-differentiated NETs were evaluated in multivariate Cox regression models. Age, sex, hormonal status, size, lymph node ratio, stage, margin status and grading were evaluated in order to predict disease-free survival (DFS). Four models were evaluated: model 1: grading according to the 2010 WHO; model 2: modified grading with cut-off at 5% of the Ki-67 index; model 3: modified grading in which the G2 category was divided into two subgroups (2-5% and 5-20%) and model 4: the Ki-67 index as a continuous variable. Decision curve analysis (DCA) was carried out to evaluate the clinical utility of the various cut-offs.
  
  
  RESULTS
  All the grading systems remained independent factors in predicting DFS. Model 2 (c index = 0.814 and P = 0.012) and model 3 (c index = 0.865 and P = 0.015) showed higher predictive powers with respect to model 1 (c index = 0.799). Model 4 had a high predictive value (c index 0.848, P = 0.013). Decision curve analysis confirmed that biological behaviour represented the best prognostic parameter.
  
  
  CONCLUSIONS
  This study presented some limitations: single centre, retrospective design and a long period of enrolment. The result showed that, by increasing the cut-off of the G2 category to 5% or by creating two subgroups in the G2 category, it was possible to obtain a better stratification of patients.
authors.affiliation: Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, University of Bologna, S.Orsola-Malpighi Hospital, Italy. Electronic address: claudiochir@gmail.com.
authors.forename: Claudio
authors.initials: C
authors.lastname: Ricci
authors.affiliation: Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, University of Bologna, S.Orsola-Malpighi Hospital, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Casadei
authors.affiliation: Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, University of Bologna, S.Orsola-Malpighi Hospital, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Taffurelli
authors.affiliation: Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, University of Bologna, S.Orsola-Malpighi Hospital, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Campana
authors.affiliation: Department of Haematology and Oncology (DIMES), Alma Mater Studiorum, University of Bologna, S.Orsola-Malpighi Hospital, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Ambrosini
authors.affiliation: Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, University of Bologna, S.Orsola-Malpighi Hospital, Italy.
authors.forename: Nico
authors.initials: N
authors.lastname: Pagano
authors.affiliation: Department of Haematology and Oncology (DIMES), Alma Mater Studiorum, University of Bologna, S.Orsola-Malpighi Hospital, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Santini
authors.affiliation: Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, University of Bologna, S.Orsola-Malpighi Hospital, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: De Giorgio
authors.affiliation: Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, University of Bologna, S.Orsola-Malpighi Hospital, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Ingaldi
authors.affiliation: Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, University of Bologna, S.Orsola-Malpighi Hospital, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Tomassetti
authors.affiliation: Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, University of Bologna, S.Orsola-Malpighi Hospital, Italy.
authors.forename: Elia
authors.initials: E
authors.lastname: Zani
authors.affiliation: Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, University of Bologna, S.Orsola-Malpighi Hospital, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Minni
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003661:Decision Support Techniques; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D018358:Neuroendocrine Tumors / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D016577:Pancreaticoduodenectomy; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D012189:Retrospective Studies; D014944:World Health Organization
chemical_list: D019394:Ki-67 Antigen
keywords: Classification; Decision curve analysis; Ki-67; Pancreatic endocrine neoplasm; Surgery; World Health Organization