Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Canadian Journal of Anesthesia/Journal canadien d'anesthésie
Published in: Canadian Journal of Anesthesia/Journal canadien d'anesthésie 5/2017

01-05-2017 | Reports of Original Investigations

Impact of celecoxib on inflammation during cancer surgery: a randomized clinical trial

Authors: Jonathan G. Hiller, MBBS, GCEpi, FANZCA, Shienny Sampurno, BSc, Rosemary Millen, BSc, Niketh Kuruvilla, MBBS, Kwok M. Ho, PhD, Rob Ramsay, PhD, Bernhard Riedel, PhD

Published in: Canadian Journal of Anesthesia/Journal canadien d'anesthésie | Issue 5/2017

Login to get access

Abstract

Purpose

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 PGEM levels were observed between the celecoxib and control groups. Linear mixed modeling, used to accommodate differences in baseline PGEM levels, showed that celecoxib (cf. control) administration lowered plasma PGEM over 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.

Discussion

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
Literature
1.
2.
Horowitz M, Neeman E, Sharon E, Ben-Eliyahu S. Exploiting the critical perioperative period to improve long-term cancer outcomes. Nat Rev Clin Oncol 2015; 12: 213-26.CrossRefPubMed
3.
Torrance HD, Pearse RM, O’Dwyer MJ. Does major surgery induce immune suppression and increase the risk of postoperative infection? Curr Opin Anaesthesiol 2016; 29: 376-83.CrossRefPubMed
4.
Tohme S, Yazdani HO, Al-Khafaji AB, et al. Neutrophil extracellular traps promote the development and progression of liver metastases after surgical stress. Cancer Res 2016; 76: 1367-80.CrossRefPubMedPubMedCentral
5.
Glasner A, Avraham R, Rosenne E, et al. Improving survival rates in two models of spontaneous postoperative metastasis in mice by combined administration of a beta-adrenergic antagonist and a cyclooxygenase-2 inhibitor. J Immunol 2010; 184: 2449-57.CrossRefPubMed
6.
Gottschalk A, Brodner G, Van Aken HK, Ellger B, Althaus S, Schulze HJ. Can regional anaesthesia for lymph-node dissection improve the prognosis in malignant melanoma? Br J Anaesth 2012; 109: 253-9.CrossRefPubMed
7.
Hiller JG, Hacking MB, Link EK, Wessels KL, Riedel BJ. Perioperative epidural analgesia reduces cancer recurrence after gastro-oesophageal surgery. Acta Anaesthesiol Scand 2014; 58: 281-90.CrossRefPubMed
8.
Forget P, Vandenhende J, Berliere M, et al. Do intraoperative analgesics influence breast cancer recurrence after mastectomy? A retrospective analysis. Anesth Analg 2010; 110: 1630-5.CrossRefPubMed
9.
Melhem-Bertrandt A, Chavez-Macgregor M, Lei X, et al. Beta-blocker use is associated with improved relapse-free survival in patients with triple-negative breast cancer. J Clin Oncol 2011; 29: 2645-52.CrossRefPubMedPubMedCentral
10.
Moselli NM, Baricocchi E, Ribero D, Sottile A, Suita L, Debernardi F. Intraoperative epidural analgesia prevents the early proinflammatory response to surgical trauma. Results from a prospective randomized clinical trial of intraoperative epidural versus general analgesia. Ann Surg Oncol 2011; 18: 2722-31.CrossRefPubMed
11.
Buvanendran A, Kroin JS, Berger RA, et al. Upregulation of prostaglandin E2 and interleukins in the central nervous system and peripheral tissue during and after surgery in humans. Anesthesiology 2006; 104: 403-10.CrossRefPubMed
12.
13.
Hansen-Petrik MB, McEntee MF, Jull B, Shi H, Zemel MB, Whelan J. Prostaglandin E(2) protects intestinal tumors from nonsteroidal anti-inflammatory drug-induced regression in Apc(Min/+) mice. Cancer Res 2002; 62: 403-8.PubMed
14.
Ferrandina G, Lauriola L, Distefano MG, et al. Increased cyclooxygenase-2 expression is associated with chemotherapy resistance and poor survival in cervical cancer patients. J Clin Oncol 2002; 20: 973-81.CrossRefPubMed
15.
Karnezis T, Shayan R, Caesar C, et al. VEGF-D promotes tumor metastasis by regulating prostaglandins produced by the collecting lymphatic endothelium. Cancer Cell 2012; 21: 181-95.CrossRefPubMed
16.
Wu YC, Su LJ, Wang HW, et al. Co-overexpression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 adversely affects the postoperative survival in non-small cell lung cancer. J Thorac Oncol 2010; 5: 1167-74.CrossRefPubMed
17.
Costa C, Soares R, Reis-Filho JS, Leitao D, Amendoeira I, Schmitt FC. Cyclo-oxygenase 2 expression is associated with angiogenesis and lymph node metastasis in human breast cancer. J Clin Pathol 2002; 55: 429-34.CrossRefPubMedPubMedCentral
18.
Ogino S, Kirkner GJ, Nosho K, et al. Cyclooxygenase-2 expression is an independent predictor of poor prognosis in colon cancer. Clin Cancer Res 2008; 14: 8221-7.CrossRefPubMedPubMedCentral
19.
Zhao H, Feng Y, Wang Y, Yang B, Xing Z. Comparison of different loading dose of celecoxib on postoperative anti-inflammation and analgesia in patients undergoing endoscopic nasal surgery-200 mg is equivalent to 400 mg. Pain Med 2011; 12: 1267-75.CrossRefPubMed
20.
Wang D, DuBois RN. Urinary PGE-M: a promising cancer biomarker. Cancer Prev Res (Phila) 2013; 6: 507-10.CrossRef
21.
Seyberth HW, Sweetman BJ, Frolich JC, Oates JA. Quantifications of the major urinary metabolite of the E prostaglandins by mass spectrometry: evaluation of the method’s application to clinical studies. Prostaglandins 1976; 11: 381-97.CrossRefPubMed
22.
Liu JF, Jamieson GG, Wu TC, Zhu GJ, Drew PA. A preliminary study on the postoperative survival of patients given aspirin after resection for squamous cell carcinoma of the esophagus or adenocarcinoma of the cardia. Ann Surg Oncol 2009; 16: 1397-402.CrossRefPubMed
23.
Backhus LM, Sievers E, Lin GY, et al. Perioperative cyclooxygenase 2 inhibition to reduce tumor cell adhesion and metastatic potential of circulating tumor cells in non-small cell lung cancer. J Thorac Cardiovasc Surg 2006; 132: 297-303.CrossRefPubMed
24.
Taniguchi T, Koido Y, Aiboshi J, Yamashita T, Suzaki S, Kurokawa A. Change in the ratio of interleukin-6 to interleukin-10 predicts a poor outcome in patients with systemic inflammatory response syndrome. Crit Care Med 1999; 27: 1262-4.CrossRefPubMed
25.
Goh BK, Chok AY, Allen JC Jr, et al. Blood neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios are independent prognostic factors for surgically resected gastrointestinal stromal tumors. Surgery 2016; 159: 1146-56.CrossRefPubMed
26.
Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004; 240: 205-13.CrossRefPubMedPubMedCentral
27.
Cai Q, Gao YT, Chow WH, et al. Prospective study of urinary prostaglandin E2 metabolite and colorectal cancer risk. J Clin Oncol 2006; 24: 5010-6.CrossRefPubMed
28.
Dong LM, Shu XO, Gao YT, et al. Urinary prostaglandin E2 metabolite and gastric cancer risk in the Shanghai women’s health study. Cancer Epidemiol Biomarkers Prev 2009; 18: 3075-8.CrossRefPubMedPubMedCentral
29.
Mao JT, Fishbein MC, Adams B, et al. Celecoxib decreases Ki-67 proliferative index in active smokers. Clin Cancer Res 2006; 12: 314-20.CrossRefPubMed
30.
Kurtova AV, Xiao J, Mo Q, et al. Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance. Nature 2015; 517: 209-13.CrossRefPubMed
31.
Altorki NK, Port JL, Zhang F, et al. Chemotherapy induces the expression of cyclooxygenase-2 in non-small cell lung cancer. Clin Cancer Res 2005; 11: 4191-7.CrossRefPubMed
32.
Reckamp KL, Krysan K, Morrow JD, et al. A phase I trial to determine the optimal biological dose of celecoxib when combined with erlotinib in advanced non-small cell lung cancer. Clin Cancer Res 2006; 12(11 Pt 1): 3381-8.CrossRefPubMed
33.
Dixon DA. Dysregulated post-transcriptional control of COX-2 gene expression in cancer. Curr Pharm Des 2004; 10: 635-46.CrossRefPubMed
34.
Munford RS, Pugin J. Normal responses to injury prevent systemic inflammation and can be immunosuppressive. Am J Respir Crit Care Med 2001; 163: 316-21.CrossRefPubMed
35.
Cai T, Mazzoli S, Meacci F, et al. Interleukin-6/10 ratio as a prognostic marker of recurrence in patients with intermediate risk urothelial bladder carcinoma. J Urol 2007; 178: 1906-11.CrossRefPubMed
36.
Que Y, Qiu H, Li Y, et al. Preoperative platelet-lymphocyte ratio is superior to neutrophil-lymphocyte ratio as a prognostic factor for soft-tissue sarcoma. BMC Cancer 2015; 15: 648.CrossRefPubMedPubMedCentral
Metadata
Title
Impact of celecoxib on inflammation during cancer surgery: a randomized clinical trial
Authors
Jonathan G. Hiller, MBBS, GCEpi, FANZCA
Shienny Sampurno, BSc
Rosemary Millen, BSc
Niketh Kuruvilla, MBBS
Kwok M. Ho, PhD
Rob Ramsay, PhD
Bernhard Riedel, PhD
Publication date
01-05-2017
Publisher
Springer US
Published in
Canadian Journal of Anesthesia/Journal canadien d'anesthésie / Issue 5/2017
Print ISSN: 0832-610X
Electronic ISSN: 1496-8975
DOI
https://doi.org/10.1007/s12630-017-0818-z

Other articles of this Issue 5/2017

Canadian Journal of Anesthesia/Journal canadien d'anesthésie 5/2017 Go to the issue

Case Reports / Case Series

Mycobacterium infection from a cardiopulmonary bypass heater-cooler unit in a patient with steroid-induced immunosuppression

Images in Anesthesia

Central retinal artery occlusion after percutaneous nephrolithotomy lithotripsy in the prone position

Special Article

Airway management outside the operating room: how to better prepare

Reports of Original Investigations

Optimal propofol induction dose in morbidly obese patients: A randomized controlled trial comparing the bispectral index and lean body weight scalar

Correspondence

Successful treatment of inadvertent subclavian artery cannulation by arterial closure device

Editorials

How to construct regression models for observational studies (and how NOT to do it!)