title: Impact of celecoxib on inflammation during cancer surgery: a randomized clinical trial.
abstract: OBJECTIVE
  During cancer surgery, prostaglandin-mediated inflammation may promote and activate micrometastatic disease with a consequent increase in long-term cancer recurrence. Cyclooxygenase-2 inhibitors, known to have anti-proliferative properties, may offset such perioperative perturbation. We investigated the effectiveness of these agents to minimize inflammatory changes during cancer surgery.
  
  
  METHODS
  Following ethics approval, 32 patients who were to undergo major intracavity cancer surgery were enrolled in this prospective, randomized, clinical trial. The treatment group received 400 mg celecoxib preoperatively followed by five 200 mg 12-hourly doses. The control group received no anti-inflammatory agents. Inflammatory and immunomodulatory end points were measured serially. The primary end points were the measured plasma and urinary prostaglandin E metabolite (PGEM) levels 48 hours following surgery. Secondary endpoints included interleukin levels, leucocyte profile, and clinical end points.
  
  
  RESULTS
  No differences in the 48-hr plasma or urinary PGEMlevels were observed between the celecoxib and control groups. Linear mixed modeling, used to accommodate differences in baseline PGEMlevels, showed that celecoxib (cf. control) administration lowered plasma PGEMover the entire 48-hr period following surgery (β-coefficient = -0.38 pg.ml-1; 95% confidence interval: -0.69 to -0.06; P = 0.021). Celecoxib administration also lowered postoperative pain scores.
  
  
  CONCLUSIONS
  Standard dosing of the cyclooxygenase-2 inhibitor celecoxib slightly reduced perioperative cyclooxygenase activity during cancer surgery. Given cyclooxygenase's role in cancer pathways, we recommend dose-finding studies be undertaken before prospective clinical trials are conducted testing the currently unsubstantiated hypothesis that perioperative anti-inflammatory administration improves long-term cancer outcomes. This trial was registered at: Australian New Zealand Clinical Trial Registry: ACTRN12615000041550; www.anzctr.org.au.
authors.affiliation: Division of Surgical Oncology, Department of Cancer Anaesthesia, Perioperative and Pain Medicine, Peter MacCallum Cancer Centre, Victorian Comprehensive Cancer Centre, 305 Grattan Street, Melbourne, 3000, VIC, Australia. jonathan.hiller@petermac.org.|Differentiation and Transcription Laboratory, Peter MacCallum Cancer Centre, Melbourne, Australia. jonathan.hiller@petermac.org.|Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia. jonathan.hiller@petermac.org.|Monash University, Melbourne, Australia. jonathan.hiller@petermac.org.
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Hiller
authors.affiliation: Differentiation and Transcription Laboratory, Peter MacCallum Cancer Centre, Melbourne, Australia.
authors.forename: Shienny
authors.initials: S
authors.lastname: Sampurno
authors.affiliation: Differentiation and Transcription Laboratory, Peter MacCallum Cancer Centre, Melbourne, Australia.
authors.forename: Rosemary
authors.initials: R
authors.lastname: Millen
authors.affiliation: Division of Surgical Oncology, Department of Cancer Anaesthesia, Perioperative and Pain Medicine, Peter MacCallum Cancer Centre, Victorian Comprehensive Cancer Centre, 305 Grattan Street, Melbourne, 3000, VIC, Australia.
authors.forename: Niketh
authors.initials: N
authors.lastname: Kuruvilla
authors.affiliation: Department of Intensive Care Medicine, Royal Perth Hospital, Perth, Australia.|School of Veterinary & Life Sciences, Murdoch University, Perth, Australia.
authors.forename: Kwok M
authors.initials: KM
authors.lastname: Ho
authors.affiliation: Differentiation and Transcription Laboratory, Peter MacCallum Cancer Centre, Melbourne, Australia.
authors.forename: Rob
authors.initials: R
authors.lastname: Ramsay
authors.affiliation: Division of Surgical Oncology, Department of Cancer Anaesthesia, Perioperative and Pain Medicine, Peter MacCallum Cancer Centre, Victorian Comprehensive Cancer Centre, 305 Grattan Street, Melbourne, 3000, VIC, Australia.|Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Riedel
mesh_terms: D000368:Aged; D000068579:Celecoxib / Q000008:administration & dosage* / Q000494:pharmacology; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000601:surgery*; D010149:Postoperative Pain / Q000517:prevention & control; D011446:Prospective Studies; D013373:Substance P / Q000378:metabolism
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D013373:Substance P; D000068579:Celecoxib