REVIEW 1130-0108/2017/109/11/778-787 REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS © Copyright 2017. SEPD y © ARÁN EDICIONES, S.L. REV ESP ENFERM DIG 2017, Vol. 109, N.º 11, pp. 778-787 Hurtado-Pardo L, Cienfuegos JA, Ruiz-Canela M, Panadero P, Benito A, Hernández-Lizoain JL. Cystic pancreatic neuroendocrine tumors (cPNETs): a systematic review and meta-analysis of case series. Rev Esp Enferm Dig 2016;109(11):778-787. DOI: 10.17235/reed.2017.5044/2017 Received: 08-05-2017 Accepted: 07-08-2017 Correspondence: Javier A. Cienfuegos. Department of General Surgery. Clínica Universidad de Navarra. University of Navarra. Av. Pío XII, 36. 31008 Pamplona, Spain e-mail: fjacien@unav.es Cystic pancreatic neuroendocrine tumors (cPNETs): a systematic review and meta-analysis of case series Luis Hurtado-Pardo 1 , Javier A. Cienfuegos 1-3 , Miguel Ruiz-Canela 2,3 , Pablo Panadero 4 , Alberto Benito 5 and José Luis Hernández-Lizoain 1 1 Department of General Surgery. Clínica Universidad de Navarra. Pamplona, Spain. 2 Department of Preventive Medicine and Public Health. Universidad de Navarra. Pamplona, Spain. 3 Institute of Health Research of Navarra (IdisNA). Pamplona, Spain. 4 Department of Pathology, and 5 Department of Radiology. Clínica Universidad de Navarra. Pamplona, Spain ABSTRACT Cystic pancreatic neuroendocrine tumors represent 13% of all neuroendocrine tumors. The aim of this study is to analyze the phenotype and biologic behavior of resected cystic neuroendocrine tumors. A systematic review and meta-analysis were conducted until September 2016 using a search in Medline, Scopus, and EMBASE with the terms “cystic pancreatic endocrine neoplasm”, “cystic islets tumors” and “cystic islets neoplasms”. From the 795 citations recovered 80 studies reporting on 431 patients were selected. 87.1% (n = 387) were sporadic tumors and 10.3% (n = 40) corresponded to multiple endocrine neoplasia type 1. Were diagnosed incidentally 44.6% (n = 135). Cytology was found to have a sensitivity of 78.5%. Were non-functional tumors 85% (n = 338), and among the functional tumors, insulinoma was the most frequent. According to the European Neuroendocrine Tumor Society staging, 87.8% were limited to the pancreas (I-IIb), and 12.2% were advanced (III-IV). Disease-free survival at 5 years in stages (I-IIIa) and (IIIb-IV) was 91.5% and 54.2%, respectively; and was significantly lower (p = 0.0001) in functional tumors. In patients with multiple endocrine neoplasia there was a higher incidence of functional (62.5%) and multifocal (28.1%) tumors. Disease-free survival at 5 and 10 years was 60%. Cystic pancreatic neuroendocrine tumors exhibit phenotypical characteristics which are different to those of solid neuroendocrine tumors. Key words: Cystic pancreatic neuroendocrine tumors. Multiple endocrine neoplasia type 1. Cystic tumors. Oncologic outcomes. Evidence base medicine. INTRODUCTION Cystic pancreatic neuroendocrine tumors (cPNETs) account for between 13% and 17% of pancreatic neuro- endocrine tumors (PNETs) and 9-10% of resected cystic tumors (1,2). Due to the widespread use of diagnostic methods with greater sensitivity and specificity the incidence of such tumors has risen in recent years and has led to the publi- cation of cases and clinical series. Establishing a differential diagnosis with regard to other cystic and solid lesions of the pancreas may be difficult as in many cases cPNETs are diagnosed incidentally and exhibit great clinical variability: functional, non-function- al, sporadic or hereditary (3-5). The aim of the present study is to carry out a systematic review and meta-analysis of resected cystic pancreatic neu- roendocrine tumors reported in the literature, including 5 cases from our own center, with the objective of obtaining the most exhaustive scientific knowledge on their clinical, pathologic and prognostic characteristics. MATERIAL AND METHODS The systematic review was carried out following the recommen- dations reported in the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses” (PRISMA) adapted to surgical series and cases (6,7). Cystic pancreatic neuroendocrine tumor was defined as any neu- roendocrine tumor which had a cystic pattern (purely cystic or mixed cystic-solid lesions) in the macroscopic study or the imaging studies and confirmed by histology. – Inclusion criteria: all published cases of cystic pancreatic neuroendocrine tumors which were treated with surgery and with histologic confirmation were identified. Non-resected tumors or those where histologic confirmation was lacking were excluded. – Methods use to search for and identify studies: up to 22 nd Sep- tember 2016, the following databases were consulted: Medline, Scopus, and EMBASE. Studies in English, German French and Spanish were included. A search of the “grey” literature was also undertaken with the inclusion of cases reported at con- ferences, letters to the editor or chapters in books. The search terms used were “cystic pancreatic endocrine neoplasms”, “cystic islets tumors”, and “cystic islets neoplasms”. The articles identified were recorded in an Excel® database and duplicates were eliminated. In the database, the titles and abstracts of the articles were independently reviewed by two