title: Extranodal Extension of Nodal Metastases Is a Poor Prognostic Indicator in Gastric Cancer: a Systematic Review and Meta-analysis.
abstract: The extranodal extension (ENE) of nodal metastases (the extension of neoplastic cells through the nodal capsule into the perinodal soft tissue) is a histological feature that has been considered a prognostic factor in several cancers, but the role in gastric cancer was not yet investigated. We aimed to investigate the prognostic role of ENE in patients affected by gastric cancer through a systematic review and meta-analysis.
  
  
  
  Two independent authors searched major databases until 09/30/2015 to identify studies providing data on gastric cancer patients' prognostic parameters and comparing patients with ENE (ENE+) vs intra-nodal extension (ENE-). The data were summarized using risk ratios (RRs) for the number of deaths/recurrences and hazard ratios (HRs) with 95 % confidence intervals (CI), adjusted for potential confounders.
  
  
  
  Nine studies followed up 3250 patients with gastric cancer (1064 ENE+ and 2186 ENE-). ENE+ was associated with a significantly higher risk of all-cause mortality (RR = 1.70; 95 % CI: 1.43-2.03, I (2) = 66 %; HR = 2.14; 95 % CI: 1.66-2.75, I (2) = 0 %), cancer-specific mortality (RR = 1.59; 95 % CI: 1.42-1.79; HR = 1.52; 95 % CI: 1.19-1.96), and disease recurrence (RR = 3.43, 95 % CI: 1.80-6.54, I (2) = 0 %).
  
  
  
  Judging from our results, ENE in gastric cancer patients should be considered for prognostic purposes from the gross sample to the pathology report.
authors.affiliation: Department of Medicine, DIMED, University of Padua, Padua, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Veronese
authors.affiliation: Department of Medicine, DIMED, University of Padua, Padua, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Fassan
authors.affiliation: Department of Pathology, The Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Laura D
authors.initials: LD
authors.lastname: Wood
authors.affiliation: Health Service and Population Research Department, King's College London, De Crespigny Park, London, UK.
authors.forename: Brendon
authors.initials: B
authors.lastname: Stubbs
authors.affiliation: Department of Neuroscience, University of Padua, Padua, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Solmi
authors.affiliation: Department of Diagnostics and Public Health, University and Hospital Trust of Verona, Piazzale Scuro, 10, 37134, Verona, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Capelli
authors.affiliation: Department of Surgery, University and Hospital trust of Verona, Verona, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Pea
authors.affiliation: Department of Diagnostics and Public Health, University and Hospital Trust of Verona, Piazzale Scuro, 10, 37134, Verona, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Nottegar
authors.affiliation: Department of Medicine, DIMED, University of Padua, Padua, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sergi
authors.affiliation: Department of Medicine, DIMED, University of Padua, Padua, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Manzato
authors.affiliation: Department of Medicine, DIMED, University of Padua, Padua, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Carraro
authors.affiliation: Medical Oncology Unit, Department of Clinical and Experimental Oncology, Istituto Oncologico Veneto IOV-IRCCS, Padova, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Maruzzo
authors.affiliation: Department of Diagnostics and Public Health, University and Hospital Trust of Verona, Piazzale Scuro, 10, 37134, Verona, Italy.
authors.forename: Ivana
authors.initials: I
authors.lastname: Cataldo
authors.affiliation: Department of Surgery, University and Hospital trust of Verona, Verona, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Bagante
authors.affiliation: Department of Pathology, Santa Chiara Hospital, Trento, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Barbareschi
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Division of General and Upper GI Surgery, Department of Surgery, University and Hospital trust of Verona, Verona, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Bencivenga
authors.affiliation: Division of General and Upper GI Surgery, Department of Surgery, University and Hospital trust of Verona, Verona, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: de Manzoni
authors.affiliation: Department of Diagnostics and Public Health, University and Hospital Trust of Verona, Piazzale Scuro, 10, 37134, Verona, Italy. claudio.luchini@katamail.com.|Department of Pathology, Santa Chiara Hospital, Trento, Italy. claudio.luchini@katamail.com.|ARC-NET Research Center, University and Hospital Trust of Verona, Verona, Italy. claudio.luchini@katamail.com.
authors.forename: Claudio
authors.initials: C
authors.lastname: Luchini
mesh_terms: D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D016017:Odds Ratio; D011379:Prognosis; D016016:Proportional Hazards Models; D012008:Recurrence; D013274:Stomach Neoplasms / Q000473:pathology*
keywords: ENE; Extranodal extension; Gastric cancer; Lymph node metastasis