title: Circulating IL-6 concentrations link tumour necrosis and systemic and local inflammatory responses in patients undergoing resection for colorectal cancer.
abstract: BACKGROUND
  Cancer-associated inflammation, in the form of local and systemic inflammatory responses, appear to be linked to tumour necrosis and have prognostic value in patients with colorectal cancer. However, their relationship with circulating biochemical mediators is unclear. The aim of the present study was to examine the interrelationships between circulating mediators, in particular interleukin-6 (IL-6) and tumour necrosis, and local and systemic inflammatory responses in patients undergoing resection for colorectal cancer.
  
  
  METHODS
  Data were collected from preoperative blood tests for 118 patients who underwent resection for colorectal cancer. Analysis of circulating IL-6, IL-10, vascular endothelial growth factor (VEGF), differential white cell count, C-reactive protein, and albumin were carried out. Routine pathology specimens were examined for tumour characteristics including necrosis and the extent of the inflammatory cell infiltrate. Body composition was examined using body mass index (BMI), total body fat, subcutaneous body fat, visceral fat, and skeletal muscle mass.
  
  
  RESULTS
  Circulating IL-6 concentrations were significantly associated with increased T stage (P<0.05), tumour necrosis (P<0.001), IL-10 (P<0.001), VEGF (P<0.001), modified Glasgow Prognostic Score (mGPS; P<0.001), white cell (P<0.01) and platelet (P<0.01) counts, and low skeletal muscle index (P<0.01). When normalised for T stage, tumour necrosis was associated with IL-6 (P<0.001), IL-10 (P<0.01), VEGF (P<0.001), mGPS (P<0.001), neutrophil-lymphocyte ratio (NLR; P<0.05), white cell (P<0.001), neutrophil (P<0.05), and platelet counts (P<0.005), and skeletal muscle index (P<0.001).
  
  
  CONCLUSIONS
  The present study provides, for the first time, supportive evidence for the hypothesis that tumour necrosis, independent of T stage, is associated with elevated circulating IL-6 concentrations, thereby modulating both local and systemic inflammatory responses including angiogenesis that, in turn, may promote tumour progression and metastases.
authors.affiliation: Academic Unit of Surgery, School of Medicine, University of Glasgow, Royal Infirmary, Glasgow, G31 2ER, UK. graemeguthrie@doctors.org.uk
authors.forename: G J K
authors.initials: GJ
authors.lastname: Guthrie
authors.forename: C S D
authors.initials: CS
authors.lastname: Roxburgh
authors.forename: C H
authors.initials: CH
authors.lastname: Richards
authors.forename: P G
authors.initials: PG
authors.lastname: Horgan
authors.forename: D C
authors.initials: DC
authors.lastname: McMillan
mesh_terms: D000368:Aged; D001823:Body Composition; D002097:C-Reactive Protein / Q000032:analysis; D015179:Colorectal Neoplasms / Q000097:blood* / Q000601:surgery; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood*; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood*; D007958:Leukocyte Count; D018655:Lymphocyte Count; D008214:Lymphocytes; D008297:Male; D009336:Necrosis; D009504:Neutrophils; D010976:Platelet Count; D012709:Serum Albumin / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D015850:Interleukin-6; D012709:Serum Albumin; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016753:Interleukin-10; D002097:C-Reactive Protein