Increased incidence trend of low - grade and high-grade neuroendocrine neoplasms
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		    ORIGINAL ARTICLE
 
 Increased incidence trend of low-grade and high-grade neuroendocrine neoplasms Emanuele Leoncini1 Paolo Boffetta2 Michail Shafir3 Katina Aleksovska1 Stefania Boccia1 Guido Rindi 4,5 ●
 
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 Received: 5 January 2017 / Accepted: 22 February 2017 © The Author(s) 2017; This article is published with open access at Springerlink.com
 
 Abstract Purpose The incidence of neuroendocrine neoplasms is increasing. This work aimed at: (i) establishing worldwide incidence trend of low-grade neuroendocrine neoplasms; (ii) defining the incidence and temporal trend of high-grade neuroendocrine neoplasms in USA utilizing the Surveillance Epidemiology and End Results database; (iii) comparing trends for low-grade vs. high-grade neuroendocrine neoplasms. Methods We conducted a literature search on MEDLINE and Scopus databases and incidence trends were plotted for 1973-2012. The Surveillance Epidemiology and End Results database was used to identify incidence rates in USA for 1973-2012. Incidence rates were stratified according to histological grade, gender and ethnicity. Trends were summarized as annual percent change and corresponding 95% confidence interval.
 
 Electronic supplementary material The online version of this article (doi:10.1007/s12020-017-1273-x) contains supplementary material, which is available to authorized users.
 
 Results 11 studies were identified involving 72,048 cases; neuroendocrine neoplasm incidence rates increased over time in all countries for all sites, except for appendix. In Surveillance Epidemiology and End Results low-grade neuroendocrine neoplasm incidence rate increased from 1.09 in 1973 to 3.51 per 100,000 in 2012. During this interval, high-grade neuroendocrine neoplasm incidence rate increased from 2.54 to 10.52 per 100,000. African Americans had the highest rates of digestive neuroendocrine neoplasms with male prevalence in high-grade. Conclusions Our data indicate an increase in the incidence of neuroendocrine neoplasms as a worldwide phenomenon, affecting most anatomical sites and involving both lowgrade and high-grade neoplasms. Keywords Neuroendocrine Cancer Low-grade Highgrade Incidence ●
 
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 Introduction
 
 Stefania Boccia and Guido Rindi contributed equally to this work. * Guido Rindi [email protected] 1
 
 Section of Hygiene, Institute of Public Health, Rome 00168, Italy
 
 2
 
 Tisch Cancer Institute, New York, NY 10029, USA
 
 3
 
 Departments of Surgery and Neoplastic Diseases, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY 10029, USA
 
 4
 
 Institute of Anatomic Pathology, Università Cattolica del Sacro Cuore, Largo A. Gemelli, 8, Rome 00168, Italy
 
 5
 
 European NeuroEndocrine Tumor Society (ENETS) Center of Excellence, Rome, Italy
 
 Neuroendocrine define those neoplasms exclusively made by cells with a neuroendocrine phenotype, i.e., expressing markers of neuroendocrine differentiation like chromogranin A, synaptophysin, neuron specific enolase and others including hormones. As such, neuroendocrine neoplasms (NENs) may develop at any anatomical s		
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