title: Prognostic Role of Primary Tumor Location in Non-Metastatic Gastric Cancer: A Systematic Review and Meta-Analysis of 50 Studies.
abstract: BACKGROUND
  The incidence of gastric cancer (GC) arising in the upper third of the stomach, including the cardia or gastroesophageal junction (GEJ), has increased in the last decades due to established etiological risk factors such as diet, obesity, and gastroesophageal reflux. We conducted a systematic review and meta-analysis to determine the prognostic role of site of origin in patients with proximal versus distal GC.
  
  
  METHODS
  We conducted a search of the PubMed, Cochrane Library, SCOPUS, Web of Science, EMBASE, Google Scholar, LILACS, and CINAHL databases from inception to September 2016. Studies reporting data on the independent prognostic effect of site in GC and comparing overall survival (OS) in proximal versus distal tumors were eligible. Data were pooled using OS hazard ratios (HRs) of proximal versus distal GC according to fixed- or random-effect model.
  
  
  RESULTS
  Overall, 50 studies including 128,268 patients were identified. Cancers located in the upper third of the stomach were associated with a significantly increased risk of all-cause mortality (HR 1.31, 95% confidence interval [CI] 1.17-1.46, p < 0.001, I2= 91%). After exclusion of GEJ tumors, prognosis was worse for pure cardia location (HR 1.39, 95% CI 1.22-1.58, p < 0.001, I2= 61%) compared with proximal or upper-third GCs without a specific subsite definition (HR 1.18, 95% CI 1.01-1.37, p = 0.04, I2= 91%).
  
  
  CONCLUSIONS
  Location of the primary GC in the upper third of the stomach, particularly at the GEJ/cardia, should be acknowledged as an important prognostic factor. Based on these results, more effective treatment strategies for proximal GCs are needed.
authors.affiliation: Oncology Unit, Oncology Department, ASST Bergamo Ovest, Treviglio (BG), Italy. faupe@libero.it.
authors.forename: Fausto
authors.initials: F
authors.lastname: Petrelli
authors.affiliation: Oncology Unit, Oncology Department, ASST Ospedale di Cremona, Cremona, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Ghidini
authors.affiliation: Oncology Unit, Oncology Department, ASST Bergamo Ovest, Treviglio (BG), Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Barni
authors.affiliation: Surgical Oncology Unit, Surgery Department, ASST Bergamo Ovest, Treviglio (BG), Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Steccanella
authors.affiliation: Surgical Oncology Unit, Surgery Department, ASST Bergamo Ovest, Treviglio (BG), Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sgroi
authors.affiliation: Oncology Unit, Oncology Department, ASST Ospedale di Cremona, Cremona, Italy.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Passalacqua
authors.affiliation: Oncology Unit, Oncology Department, ASST Ospedale di Cremona, Cremona, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Tomasello
mesh_terms: D002299:Cardia / Q000473:pathology*; D004943:Esophagogastric Junction / Q000473:pathology*; D006801:Humans; D011379:Prognosis; D013274:Stomach Neoplasms / Q000473:pathology*; D015996:Survival Rate