title: Prognostic factors for pancreatic neuroendocrine neoplasms (pNET) and the risk of small non-functioning pNET.
abstract: BACKGROUND
  Non-functioning (NF) pancreatic neuroendocrine tumors (pNET) often have an indolent outcome. A consensus to submit patients with large (>2 cm) NF-pNET to surgery already exists; but a conservative approach for small (≤2 cm) NF neoplasms has been proposed.
  
  
  OBJECTIVE
  To identify prognostic factors for survival and progression free survival (PFS) of NF-pNET, evaluating whether surgery may be avoided for small NF-pNET.
  
  
  METHODS
  Retrospective study of 77 consecutive patients with pNET submitted to surgery, of which 60 were NF. Pathological tissues were revised according to the 2000 and 2010 WHO classifications. Risk factors for survival and PFS were evaluated using the Kaplan-Meier method and the Cox regression model.
  
  
  RESULTS
  The 8-year cause-specific survival of NF-pNET was 79.3%. At univariate analysis, high grading, high staging, large tumors, angioinvasion and peri-pancreatic infiltration were significantly associated with a shorter survival; at multivariate analysis only peri-pancreatic infiltration was significantly associated with a shorter NF-pNET survival. Most small NF-pNET were grade 1 (74%), compared to large NF-pNET (27%). Distant metastases were present in 29.7% (n = 11) and 17.4% (n = 4) of patients with large or small NF-pNET, respectively; among the 19 small NF-pNET without metastasis, five had a local malignancy (lymph node metastasis or local infiltration); thus, 39% of the 23 NF-pNET, turned out to have a malignant potential.
  
  
  CONCLUSIONS
  Among NF-pNET, large neoplasms were associated with worse outcomes; however, small NF-pNET do not seem to have an invariable benign behavior. Whether surgery should be avoided in all patients with small NF-pNET is questionable.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Ospedale Cisanello, Via Paradisa 2, 56124, Pisa, Italy. marty81@tiscali.it.
authors.forename: M
authors.initials: M
authors.lastname: Lombardi
authors.affiliation: Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
authors.forename: N
authors.initials: N
authors.lastname: De Lio
authors.affiliation: Department of Surgical, Medical and Molecular Pathology of Critical Area, University of Pisa, Pisa, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Funel
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Ospedale Cisanello, Via Paradisa 2, 56124, Pisa, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Sardella
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Ospedale Cisanello, Via Paradisa 2, 56124, Pisa, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Russo
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Ospedale Cisanello, Via Paradisa 2, 56124, Pisa, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Urbani
authors.affiliation: Unit of Epidemiology and Biostatistics, Institute of Clinical Physiology, National Research Council, Pisa, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Rossi
authors.affiliation: Department of Surgical, Medical and Molecular Pathology of Critical Area, University of Pisa, Pisa, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Campani
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Ospedale Cisanello, Via Paradisa 2, 56124, Pisa, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Martino
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Ospedale Cisanello, Via Paradisa 2, 56124, Pisa, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Marcocci
authors.affiliation: Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
authors.forename: U
authors.initials: U
authors.lastname: Boggi
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Ospedale Cisanello, Via Paradisa 2, 56124, Pisa, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Bogazzi
mesh_terms: D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D010190:Pancreatic Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate
keywords: Grading; Pancreatic neuroendocrine tumors; Staging; Surgery; Treatment