title: Prognostic value of tumour necrosis and host inflammatory responses in colorectal cancer.
abstract: BACKGROUND
  Tumour necrosis is a marker of poor prognosis in some tumours but the mechanism is unclear. This study examined the prognostic value of tumour necrosis and host inflammatory responses in colorectal cancer.
  
  
  METHODS
  This was a retrospective study of patients undergoing potentially curative resection of colorectal cancer at a single surgical institution over a 10-year period. Patients who underwent preoperative radiotherapy were excluded. The systemic and local inflammatory responses were assessed using the modified Glasgow Prognostic Score and Klintrup-Makinen criteria respectively. Original tumour sections were retrieved and necrosis graded as absent, focal, moderate or extensive. Associations between necrosis and clinicopathological variables were examined, and multivariable survival analyses carried out.
  
  
  RESULTS
  A total of 343 patients were included between 1997 and 2007. Tumour necrosis was graded as absent in 32 (9·3 per cent), focal in 166 (48·4 per cent), moderate in 101 (29·4 per cent) and extensive in 44 (12·8 per cent). There were significant associations between tumour necrosis and anaemia (P = 0·022), white cell count (P = 0·006), systemic inflammatory response (P < 0·001), local inflammatory cell infiltrate (P = 0·004), tumour node metastasis (TNM) stage (P = 0·015) and Petersen Index (P = 0·003). On univariable survival analysis, tumour necrosis was associated with cancer-specific survival (P < 0·001). On multivariable survival analysis, age (hazard ratio (HR) 1·29, 95 per cent confidence interval 1·00 to 1·66), systemic inflammatory response (HR 1·74, 1·27 to 2·39), low-grade local inflammatory cell infiltrate (HR 2·65, 1·52 to 4·63), TNM stage (HR 1·55, 1·02 to 2·35) and high-risk Petersen Index (HR 3·50, 2·21 to 5·55) were associated with reduced cancer-specific survival.
  
  
  CONCLUSIONS
  The impact of tumour necrosis on colorectal cancer survival may be due to close associations with the host systemic and local inflammatory responses.
authors.affiliation: University Department of Surgery, Glasgow Royal Infirmary, Glasgow, UK. colinhrichards@hotmail.com
authors.forename: C H
authors.initials: CH
authors.lastname: Richards
authors.forename: C S D
authors.initials: CS
authors.lastname: Roxburgh
authors.forename: J H
authors.initials: JH
authors.lastname: Anderson
authors.forename: R F
authors.initials: RF
authors.lastname: McKee
authors.forename: A K
authors.initials: AK
authors.lastname: Foulis
authors.forename: P G
authors.initials: PG
authors.lastname: Horgan
authors.forename: D C
authors.initials: DC
authors.lastname: McMillan
mesh_terms: D000328:Adult; D000368:Aged; D003106:Colon / Q000473:pathology*; D003110:Colonic Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009336:Necrosis / Q000473:pathology; D011379:Prognosis; D012004:Rectal Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D012007:Rectum / Q000473:pathology*; D012189:Retrospective Studies; D018746:Systemic Inflammatory Response Syndrome / Q000401:mortality / Q000473:pathology*