title: The relationship between tumour necrosis, tumour proliferation, local and systemic inflammation, microvessel density and survival in patients undergoing potentially curative resection of oesophageal adenocarcinoma.
abstract: BACKGROUND
  There is increasing evidence that the local and systemic inflammatory responses are associated with survival in oesophageal cancer. The aim of this study was to examine the relationship between tumour necrosis, tumour proliferation, local and systemic inflammation and microvessel density and survival in patients undergoing potentially curative resection of oesophageal adenocarcinoma.
  
  
  METHODS
  The interrelationship between tumour necrosis, tumour proliferation, local inflammatory response (Klintrup-Makinen criteria, intra-tumoural CD8+ lymphocyte and macrophage infiltration), systemic inflammatory response (modified Glasgow Prognostic score (mGPS)), and microvessel density was examined in 121 patients undergoing potentially curative resection for oesophageal adenocarcinoma (including type I and II tumours of the gastro-oesophageal junction).
  
  
  RESULTS
  Tumour necrosis was not significantly associated with any tumour measure other than the degree of differentiation. On multivariate analysis, only age (HR 1.93, 95% CI 1.23-3.04, P=0.004), mGPS (HR 2.91, 95% CI 1.51-5.62, P=0.001), positive to total lymph node ratio (HR 2.38, 95% CI 1.60-3.52, P<0.001) and macrophage infiltration (HR 1.49, 95% CI 1.02-2.18, P=0.041) were independently associated with cancer-specific survival in oesophageal adenocarcinoma. Intra-tumoural macrophages were associated with tumour proliferation (P<0.001) and CD8+ lymphocytes infiltration (P<0.01).
  
  
  CONCLUSIONS
  The results of this study suggest that tumour necrosis does not link local and systemic inflammatory responses and is not significantly associated with survival. In contrast, tumour macrophage infiltration appears to have a central role in the proliferative activity and the coordination of the inflammatory cell infiltrate and is independently associated with poorer survival in patients with oesophageal adenocarcinoma.
authors.affiliation: University Department of Surgery, Faculty of Medicine, University of Glasgow, Royal Infirmary, Glasgow, UK. sdutta09@gmail.com
authors.forename: S
authors.initials: S
authors.lastname: Dutta
authors.forename: J J
authors.initials: JJ
authors.lastname: Going
authors.forename: A B C
authors.initials: AB
authors.lastname: Crumley
authors.forename: Z
authors.initials: Z
authors.lastname: Mohammed
authors.forename: C
authors.initials: C
authors.lastname: Orange
authors.forename: J
authors.initials: J
authors.lastname: Edwards
authors.forename: G M
authors.initials: GM
authors.lastname: Fullarton
authors.forename: P G
authors.initials: PG
authors.lastname: Horgan
authors.forename: D C
authors.initials: DC
authors.lastname: McMillan
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D000368:Aged; D049109:Cell Proliferation; D004938:Esophageal Neoplasms / Q000276:immunology / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D004943:Esophagogastric Junction; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000401:mortality; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008297:Male; D055806:Microvessels / Q000502:physiology; D008875:Middle Aged; D009336:Necrosis; D011379:Prognosis