The Impact of Peri-operative Anti-TNF Treatment on Anastomosis-Related Complications in Crohn’s Disease Patients. A Critical Review
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Tumor necrosis factor (TNF)α is a cytokine exerting pleiotropic effects on critical cell functions and, most importantly, is the main regulator of pro-inflammatory cytokine production and a key player in the pathophysiology of numerous autoimmune diseases, including Crohn’s disease.
TNFα became a therapeutic target and TNFα blocking agents are currently used in the treatment of inflammatory diseases. Beyond the therapeutic benefits deriving from TNFα neutralization, amendments in the cellular functions of the immune system may as well induce potent immunosuppressive effects. An attenuated immune response may compromise the intestinal healing ability, thus leading to weaker anastomosis and increased risk of anastomotic leak and septic complications.
This hypothesis raises great concerns about the safety of perioperative administration of anti-TNF and has been the endpoint of numerous studies.
The aim of this review is to critically evaluate the evidence regarding the role of TNFα in anastomosis related complications after abdominal surgery in Crohn’s disease patients.
- O'Malley WE, Achinstein B, Shear MJ. Journal of the National Cancer Institute, Vol. 29, 1962: Action of bacterial polysaccharide on tumors: II. Damage of sarcoma 37 by serum of mice treated with Serratia marcescens polysaccharide, and induced tolerance. Nutr Rev 1988 Nov; 46(11): 389–391.
- Carswell E, Old LJ, Kassel RL, Green S, Fiore N, Williamson B. An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci 1975; 72(9): 3666. CrossRef
- Pennica D, Nedwin GE, Hayflick JS, Seeburg PH, Derynck R, Palladino MA, Kohr WJ, Aggarwal BB, Goeddel DV. Human tumour necrosis factor: precursor structure, expression and homology to lymphotoxin. Nature 1984; 312(5996): 724–729. CrossRef
- Wajant H, Pfizenmaier K, Scheurich P. Tumor necrosis factor signaling. Cell Death Differ 2003 Jan; 10(1): 45–65.
- Bradley JR. TNF-mediated inflammatory disease. J Pathol 2008 Jan; 214(2): 149–160.
- Plevy SE, Landers CJ, Prehn J, Carramanzana NM, Deem RL, Shealy D, Targan SR. A role for TNF-alpha and mucosal T helper-1 cytokines in the pathogenesis of Crohn's disease. J Immunol 1997 Dec 15; 159(12): 6276–6282.
- Braegger C, Nicholls S, Murch S, MacDonald T, Stephens S. Tumour necrosis factor alpha in stool as a marker of intestinal inflammation. Lancet 1992; 339(8785): 89–91. CrossRef
- Tracey D, Klareskog L, Sasso EH, Salfeld JG, Tak PP. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther 2008 Feb; 117(2): 244–279.
- Hanauer SB, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, Colombel JF, Rachmilewitz D, Wolf DC, Olson A, Bao W, Rutgeerts P. Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet 2002 May 4; 359(9317): 1541–1549.
- Rutgeerts P, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, Colombel JF, Rachmilewitz D, Wolf DC, Olson A, Bao W, Hanauer SB. Comparison of scheduled and episodic treatment strategies of infliximab in Crohn's disease. Gastroenterology 2004 Feb; 126(2): 402–413.
- Van Assche G, Vermeire S, Rutgeerts P. The potential for disease modification in Crohn's disease. Nat Rev Gastroenterol Hepatol 2010 Feb; 7(2): 79–85.
- Rutgeerts P, D'Haens G, Targan S, Vasiliauskas E, Hanauer SB, Present DH, Mayer L, Van Hogezand RA, Braakman T, DeWoody KL, Schaible TF, Van Deventer SJ. Efficacy and safety of retreatment with anti-tumor necrosis factor antibody (infliximab) to maintain remission in Crohn's disease. Gastroenterology 1999 Oct; 117(4): 761–769.
- Slim K, Nini E, Forestier D, Kwiatkowski F, Panis Y, Chipponi J. Methodological index for non-randomized studies (minors): development and validation of a new instrument. ANZ J Surg. 2003 Sept.;73(9):712–6
- Abraham NS, Byrne CJ, Young JM, Solomon MJ. Meta-analysis of well-designed nonrandomized comparative studies of surgical procedures is as good as randomized controlled trials. J Clinical Epidemiol 2010 Mar;63(3):238–45. doi: 10.1016/j.jclinepi.2009.04.005. Epub 2009 Aug 27.
- Tay GS, Binion DG, Eastwood D, Otterson MF. Multivariate analysis suggests improved perioperative outcome in Crohn's disease patients receiving immunomodulator therapy after segmental resection and/or strictureplasty. Surgery 2003 Oct; 134(4): 565–572; discussion 572–563.
- Marchal L, D'Haens G, Van Assche G, Vermeire S, Noman M, Ferrante M, Hiele M, Bueno De Mesquita M, D'Hoore A, Penninckx F, Rutgeerts P. The risk of post-operative complications associated with infliximab therapy for Crohn's disease: a controlled cohort study. Aliment Pharmacol Ther 2004 Apr 1; 19(7): 749–754.
- Colombel JF, Loftus EV, Tremaine WJ, Pemberton JH, Wolff BG, Young-Fadok T, Harmsen WS, Schleck CD, Sandborn WJ. Early postoperative complications are not increased in patients with Crohn's disease treated perioperatively with infliximab or immunosuppressive therapy. Am J Gastroenterol 2004; 99(5): 878–883.
- Appau KA, Fazio VW, Shen B, Church JM, Lashner B, Remzi F, Brzezinski A, Strong SA, Hammel J, Kiran RP. Use of infliximab within 3 months of ileocolonic resection is associated with adverse postoperative outcomes in Crohn's patients. J Gastrointest Surg 2008 Oct; 12(10): 1738–1744.
- Nasir BS, Dozois EJ, Cima RR, Pemberton JH, Wolff BG, Sandborn WJ, Loftus EV, Larson DW. Perioperative anti-tumor necrosis factor therapy does not increase the rate of early postoperative complications in Crohn's disease. J Gastrointest Surg 2010 Dec; 14(12): 1859–1865; discussion 1865–1856.
- Indar AA, Young-Fadok TM, Heppell J, Efron JE. Effect of perioperative immunosuppressive medication on early outcome in Crohn’s disease patients. World J Surg 2009; 33(5): 1049–1052.
- Canedo J, Lee SH, Pinto R, Murad R S, Rosen L, Wexner S. Surgical resection in Crohn's disease: is immunosuppressive medication associated with higher postoperative infection rates? Colorectal Dis 2011; 13(11): 1294–1298. CrossRef
- Kasparek MS, Bruckmeier A, Beigel F, Müller MH, Brand S, Mansmann U, Jauch KW, Ochsenkühn T, Kreis ME. Infliximab does not affect postoperative complication rates in Crohn's patients undergoing abdominal surgery. Inflamm Bowel Dis 2012;28(7):1207–1213. CrossRef
- Syed A, Cross R, Flasar M. Anti-tumor necrosis factor therapy is Associated with infections after abdominal surgery in Crohn’s disease patients. Am J Gastroenterol 2013; 108:583;593
- Norgard BM, Nielsen J, Qvist N, Gradel KO, Schaffalitzky OB de Muckadell, Kjeldsen J. Pre-operative use of anti-TNF-a agents and the risk of post-operative complications in patients with Crohn’s disease — a nationwide cohort study. Aliment Pharmacol Ther 2013;37:214–224 CrossRef
- Kopylov U, Ben-Horin S, Zmora O, Eliakim R, Katz LH. Anti-tumor necrosis factor and postoperative complications in Crohn's disease: systematic review and meta-analysis. Inflamm Bowel Dis 2012;18(12):2404–2413 CrossRef
- Rosenfeld G, Qian H, Bressler B. The risks of post-operative complications following pre-operative infliximab therapy for Crohn’s disease in patients undergoing abdominal surgery: a systematic review and meta-analysis. J Crohn’s Colitis 2013;7(11):868–877 CrossRef
- Owen CR, Yuan L, Basson MD. Smad3 knockout mice exhibit impaired intestinal mucosal healing. Lab Invest 2008 Oct; 88(10): 1101–1109.
- Saika S. Yin and yang in cytokine regulation of corneal wound healing: roles of TNF-alpha. Cornea 2007 Oct; 26(9 Suppl 1): S70–74.
- Leask A, Abraham DJ. TGF-beta signaling and the fibrotic response. FASEB J 2004 May; 18(7): 816–827.
- Saika S, Ikeda K, Yamanaka O, Flanders KC, Okada Y, Miyamoto T, Kitano A, Ooshima A, Nakajima Y, Ohnishi Y, Kao WW. Loss of tumor necrosis factor alpha potentiates transforming growth factor beta-mediated pathogenic tissue response during wound healing. Am J Pathol 2006 Jun; 168(6): 1848–1860.
- Theiss AL, Simmons JG, Jobin C, Lund PK. Tumor necrosis factor (TNF) alpha increases collagen accumulation and proliferation in intestinal myofibroblasts via TNF receptor 2. J Biol Chem 2005 Oct 28; 280(43): 36099–36109.
- Klotz U, Teml A, Schwab M. Clinical pharmacokinetics and use of infliximab. Clinical pharmacokinetics 2007; 46(8): 645–660. CrossRef
- Ternant D, Aubourg A, Magdelaine-Beuzelin C, Degenne D, Watier H, Picon L, Paintaud G. Infliximab pharmacokinetics in inflammatory bowel disease patients. Ther Drug Monit 2008; 30(4): 523.
- Waterman M, Xu W, Divani A, Steinhart AH, Croitoru K, Nguyen GC, McLeod RS, Greenberg GR, Cohen Z, Silverberg MS. Preoperative biological therapy and short-term outcomes of abdominal surgery in patients with inflammatory bowel disease. Gut 2013Mar; 62(3): 387–94
- The Impact of Peri-operative Anti-TNF Treatment on Anastomosis-Related Complications in Crohn’s Disease Patients. A Critical Review
Journal of Gastrointestinal Surgery
Volume 18, Issue 6 , pp 1216-1224
- Cover Date
- Print ISSN
- Online ISSN
- Springer US
- Additional Links
- Wound Healing
- Intestinal anastomoses
- Postoperative complications
- Industry Sectors
- Author Affiliations
- 1. Second Department of Surgery, Aretaieion Hospital, Medical School, University of Athens, Athens, Greece
- 2. Department of Gastroenterology, Tzaneio General Hospital, Zanni & Afentouli 1, 18536, Piraeus, Greece
- 3. Molecular Carcinogenesis Group, Laboratory of Histology and Embryology, School of Medicine, University of Athens, Athens, Greece
- 4. Experimental-Research Unit, ELPEN-Pharmaceuticals Co. Inc, Pikermi Attikis, Greece