Skip to main content

Advertisement

SpringerLink
Log in

Association between preoperative tumor necrosis factor alpha inhibitor and surgical site infection after surgery for inflammatory bowel disease: a systematic review and meta-analysis

  • Review Article
  • Published:
Surgery Today Aims and scope Submit manuscript

Abstract

Tumor necrosis factor-alpha inhibitor (TNFi) treatment is effective for ulcerative colitis (UC) and Crohn’s disease (CD). Although several meta-analyses have been performed to evaluate the association between TNFi treatment and surgical morbidity, the results are controversial. We conducted a systematic review and meta-analysis of the prevention of surgical site infection (SSI) after surgery for UC and CD in patients on TNFis, based on literature published between January 2000 and May 2019 (registered on PROSPERO, No. CRD42019134156). Overall, 2175 UC patients in 13 observational studies (OBSs) and 7084 CD patients in 16 OBSs were included. The incidences of incisional (INC) SSI and organ/space (O/S) SSI after surgery for UC were 179/1985 (9.0%) and 176/2175 (8.1%), respectively. TNFi use was not associated with the incidences of INC SSI (odds ratio (OR) 1.04, 95% confidence interval (CI) (0.47–2.32) or O/S SSI (OR 1.85, 95% CI (0.82–4.20)) after surgery for UC. The INC SSI and O/S SSI incidences after surgery for CD were 289/3089 (9.4%) and 526/7,084 (7.4%), respectively. Preoperative TNFi use was not associated with INC SSI (OR 0.98, 95% CI (0.52–1.83)) or O/S SSI incidence (OR 1.09, 95% CI (0.78–1.52)) after surgery for CD. We did not find a significant association between preoperative TNFi use and SSI in surgery for UC or CD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Van Assche G, Rutgeerts P. Anti-TNF agents in Crohn’s disease. Expert Opin Investig Drugs. 2000;9:103–11.

    PubMed  Google Scholar 

  2. Hanauer SB, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, Colombel JF, et al. Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet. 2002;359:1541–9.

    CAS  PubMed  Google Scholar 

  3. Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005;353:2462–76.

    CAS  PubMed  Google Scholar 

  4. Stidham RW, Lee TC, Higgins PD, Deshpande AR, Sussman DA, Singal AG, et al. Systematic review with network meta-analysis: the efficacy of anti-TNF agents for the treatment of Crohn’s disease. Aliment Pharmacol Ther. 2014;39:1349–62.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Narula N, Charleton D, Marshall JK. Meta-analysis: peri-operative anti-TNFα treatment and post-operative complications in patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2013;37:1057–64.

    CAS  PubMed  Google Scholar 

  6. Selvaggi F, Pellino G, Canonico S, Sciaudone G. Effect of preoperative biologic drugs on complications and function after restorative proctocolectomy with primary ileal pouch formation: systematic review and meta-analysis. Inflamm Bowel Dis. 2015;21:79–92.

    PubMed  Google Scholar 

  7. Xu Y, Yang L, An P, Zhou B, Liu G. Meta-analysis: the influence of preoperative infliximab use on postoperative complications of Crohn's disease. Inflamm Bowel Dis. 2019;25:261–9.

    PubMed  Google Scholar 

  8. Lin YS, Cheng SW, Wang YH, Chen KH, Fang CJ, Chen C. Systematic review with meta-analysis: risk of post-operative complications associated with pre-operative exposure to anti-tumor necrosis factor agents for Crohn’s Disease. Aliment Pharmacol Ther. 2019;49:966–77.

    PubMed  Google Scholar 

  9. Culver DH, Horan TC, Gaynes RP, Martone WJ, Jarvis WR, Emori TG, et al. Surgical wound infection rates by wound class, operative procedure, and patient risk index. National nosocomial infections surveillance system. Am J Med. 1991;91:152S–S158158.

    CAS  PubMed  Google Scholar 

  10. Horan TC, Gaynes RP, Martone WJ, Jarvis WR, Emori TG. CDC definitions of nosocomial surgical site infections, 1992: a modification of CDC definitions of surgical wound infections. Infect Control Hosp Epidemiol. 1992;13:606–8.

    CAS  PubMed  Google Scholar 

  11. Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2019;343:5928.

    Google Scholar 

  12. Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, et al. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol. 2011;64:383–94.

    PubMed  Google Scholar 

  13. Kanda Y. Investigation of the freely available easy-to-use software 'EZR' for medical statistics. Bone Marrow Transplant. 2013;48:452–8.

    CAS  PubMed  Google Scholar 

  14. Selvasekar CR, Cima RR, Larson DW, Dozois EJ, Harrington JR, Harmsen WS, et al. Effect of infliximab on short-term complications in patients undergoing operation for chronic ulcerative colitis. J Am Coll Surg. 2007;204:956–62.

    PubMed  Google Scholar 

  15. Mor IJ, Vogel JD, da Luz MA, Shen B, Hammel J, Remzi FH. Infliximab in ulcerative colitis is associated with an increased risk of postoperative complications after restorative proctocolectomy. Dis Colon Rectum. 2008;51:1202–7.

    CAS  PubMed  Google Scholar 

  16. Ferrante M, D'Hoore A, Vermeire S, Declerck S, Noman M, Van Assche G, et al. Corticosteroids but not infliximab increase short-term postoperative infectious complications in patients with ulcerative colitis. Inflamm Bowel Dis. 2009;15:1062–70.

    CAS  PubMed  Google Scholar 

  17. Coquet-Reinier B, Berdah SV, Grimaud JC, Birnbaum D, Cougard PA, Barthet M, et al. Preoperative infliximab treatment and postoperative complications after laparoscopic restorative proctocolectomy with ileal pouch-anal anastomosis: a case-matched study. Surg Endosc. 2010;24:1866–71.

    PubMed  Google Scholar 

  18. Gainsbury ML, Chu DI, Howard LA, Coukos JA, Farraye FA, Stucchi AF, et al. Preoperative infliximab is not associated with an increased risk of short-term postoperative complications after restorative proctocolectomy and ileal pouch-anal anastomosis. J Gastrointest Surg. 2011;15:397–403.

    PubMed  Google Scholar 

  19. Bregnbak D, Mortensen C, Bendtsen F. Infliximab and complications after colectomy in patients with ulcerative colitis. J Crohns Colitis. 2012;6:281–6.

    PubMed  Google Scholar 

  20. Schaufler C, Lerer T, Campbell B, Weiss R, Cohen J, Sayej W, et al. Preoperative immunosuppression is not associated with increased postoperative complications following colectomy in children with colitis. J Pediatr Gastroenterol Nutr. 2012;55:421–4.

    CAS  PubMed  Google Scholar 

  21. Uchino M, Ikeuchi H, Matsuoka H, Bando T, Ichiki K, Nakajima K, et al. Infliximab administration prior to surgery does not increase surgical site infections in patients with ulcerative colitis. Int J Colorectal Dis. 2013;28:1295–306.

    PubMed  Google Scholar 

  22. Gu J, Remzi FH, Shen B, Vogel JD, Kiran RP. Operative strategy modifies risk of pouch-related outcomes in patients with ulcerative colitis on preoperative anti-tumor necrosis factor-α therapy. Dis Colon Rectum. 2013;56:1243–52.

    PubMed  Google Scholar 

  23. Eshuis EJ, Al Saady RL, Stokkers PC, Ponsioen CY, Tanis PJ, Bemelman WA. Previous infliximab therapy and postoperative complications after proctocolectomy with ileum pouch anal anastomosis. J Crohns Colitis. 2013;7:142–9.

    PubMed  Google Scholar 

  24. Nelson R, Liao C, Fichera A, Rubin DT, Pekow J. Rescue therapy with cyclosporine or infliximab is not associated with an increased risk for postoperative complications in patients hospitalized for severe steroid-refractory ulcerative colitis. Inflamm Bowel Dis. 2014;20:14–20.

    PubMed  Google Scholar 

  25. Uchino M, Ikeuchi H, Bando T, Hirose K, Hirata A, Chohno T, et al. Does pre-operative multiple immunosuppressive therapy associate with surgical site infection in surgery for ulcerative colitis. Digestion. 2015;92:121–9.

    CAS  PubMed  Google Scholar 

  26. Uchino M, Ikeuchi H, Bando T, Chohno T, Sasaki H, Horio Y, et al. Associations between multiple immunosuppressive treatments before surgery and surgical morbidity in patients with ulcerative colitis during the era of biologics. Int J Colorectal Dis. 2019;34:699–710.

    PubMed  Google Scholar 

  27. Marchal L, D'Haens G, Van Assche G, Vermeire S, Noman M, Ferrante M, et al. The risk of post-operative complications associated with infliximab therapy for Crohn's disease: a controlled cohort study. Aliment Pharmacol Ther. 2004;19:749–54.

    CAS  PubMed  Google Scholar 

  28. Appau KA, Fazio VW, Shen B, Church JM, Lashner B, Remzi F, et al. Use of infliximab within 3 months of ileocolonic resection is associated with adverse postoperative outcomes in Crohn's patients. J Gastrointest Surg. 2008;12:1738–44.

    PubMed  Google Scholar 

  29. Nasir BS, Dozois EJ, Cima RR, Pemberton JH, Wolff BG, Sandborn WJ, et al. Perioperative anti-tumor necrosis factor therapy does not increase the rate of early postoperative complications in Crohn's disease. J Gastrointest Surg. 2010;14:1859–65.

    PubMed  Google Scholar 

  30. Canedo J, Lee SH, Pinto R, Murad-Regadas S, Rosen L, Wexner SD. Surgical resection in Crohn's disease: is immunosuppressive medication associated with higher postoperative infection rates? Colorectal Dis. 2011;13:1294–8.

    CAS  PubMed  Google Scholar 

  31. Syed A, Cross RK, Flasar MH. Anti-tumor necrosis factor therapy is associated with infections after abdominal surgery in Crohn's disease patients. Am J Gastroenterol. 2013;108:583–93.

    CAS  PubMed  Google Scholar 

  32. Nørgård BM, Nielsen J, Qvist N, Gradel KO, de Muckadell OB, Kjeldsen J. Pre-operative use of anti-TNF-α agents and the risk of post-operative complications in patients with Crohn's disease—a nationwide cohort study. Aliment Pharmacol Ther. 2013;37:214–24.

    PubMed  Google Scholar 

  33. Serradori T, Germain A, Scherrer ML, Ayav C, Perez M, Romain B, et al. The effect of immune therapy on surgical site infection following Crohn's Disease resection. Br J Surg. 2013;100:1089–93.

    CAS  PubMed  Google Scholar 

  34. Uchino M, Ikeuchi H, Matsuoka H, Bando T, Ichiki K, Nakajima K, et al. Risk factors for surgical site infection and association with infliximab administration during surgery for Crohn's disease. Dis Colon Rectum. 2013;56:1156–65.

    PubMed  Google Scholar 

  35. Yamamoto T, Spinelli A, Suzuki Y, Saad-Hossne R, Teixeira FV, de Albuquerque IC, et al. Risk factors for complications after ileocolonic resection for Crohn's disease with a major focus on the impact of preoperative immunosuppressive and biologic therapy: a retrospective international multicentre study. United Eur Gastroenterol J. 2016;4:784–93.

    Google Scholar 

  36. Kotze PG, Saab MP, Saab B, da Silva Kotze LM, Olandoski M, Pinheiro LV, et al. Tumor necrosis factor alpha inhibitors did not influence postoperative morbidity after elective surgical resections in Crohn's disease. Dig Dis Sci. 2017;62:456–64.

    CAS  PubMed  Google Scholar 

  37. Brouquet A, Maggiori L, Zerbib P, Lefevre JH, Denost Q, Germain A, et al. Anti-TNF therapy is associated with an increased risk of postoperative morbidity after surgery for ileocolonic Crohn disease: results of a prospective nationwide cohort. Ann Surg. 2018;267:221–8.

    PubMed  Google Scholar 

  38. Jouvin I, Lefevre JH, Creavin B, Pitel S, Chafai N, Tiret E, et al. Postoperative morbidity risks following ileocolic resection for Crohn's disease treated with Anti-TNF alpha therapy: a retrospective study of 360 Patients. Inflamm Bowel Dis. 2018;24:422–32.

    PubMed  Google Scholar 

  39. Lightner AL, McKenna NP, Tse CS, Hyman N, Smith R, Ovsepyan G, et al. Postoperative outcomes in ustekinumab-treated patients undergoing abdominal operations for Crohn's disease. J Crohns Colitis. 2018;12:402–7.

    PubMed  Google Scholar 

  40. Schad CA, Haac BE, Cross RK, Syed A, Lonsako S, Bafford AC. Early postoperative anti-TNF therapy does not increase complications following abdominal surgery in Crohn's disease. Dig Dis Sci. 2019. https://doi.org/10.1007/s10620-019-5476-2.

    Article  PubMed  Google Scholar 

  41. Yu CS, Jung SW, Lee JL, Lim SB, Park IJ, Yoon YS, et al. The influence of preoperative medications on postoperative complications in patients after intestinal surgery for Crohn's disease. Inflamm Bowel Dis. 2019. https://doi.org/10.1093/ibd/izz010.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Lightner AL, McKenna NP, Alsughayer A, Loftus EV Jr, Raffals LE, Faubion WA, et al. Anti-TNF biologic therapy does not increase postoperative morbidity in pediatric Crohn's patients. J Pediatr Surg. 2019. https://doi.org/10.1016/j.jpedsurg.2019.01.006.

    Article  PubMed  Google Scholar 

  43. Clay M, Mazouyes A, Gilson M, Gaudin P, Baillet A. Risk of postoperative infections and the discontinuation of TNF inhibitors in patients with rheumatoid arthritis: a meta-analysis. Joint Bone Spine. 2016;83:701–5.

    CAS  PubMed  Google Scholar 

  44. Goodman SM, Menon I, Christos PJ, Smethurst R, Bykerk VP. Management of perioperative tumour necrosis factor α inhibitors in rheumatoid arthritis patients undergoing arthroplasty: a systematic review and meta-analysis. Rheumatol (Oxf). 2016;55:573–82.

    Google Scholar 

  45. Global guidelines for the prevention of surgical site infection. 2019. https://apps.who.int/iris/bitstream/10665/250680/1/9789241549882-eng.pdf. Accessed 1 Dec 2016

  46. Berríos-Torres SI, Umscheid CA, Bratzler DW, Leas B, Stone EC, Kelz RR, et al. Centers for disease control and prevention guideline for the prevention of surgical site infection, 2017. JAMA Surg. 2017;152:784–91.

    PubMed  Google Scholar 

  47. Cornillie F, Shealy D, D'Haens G, Geboes K, Van Assche G, Ceuppens J, et al. Infliximab induces potent anti-inflammatory and local immunomodulatory activity but no systemic immune suppression in patients with Crohn's disease. Aliment Pharmacol Ther. 2001;15:463–73.

    CAS  PubMed  Google Scholar 

Download references

Funding

This work was partially supported by the Japan Surgical Infection Society.

Author information

Authors and Affiliations

  1. Department of Inflammatory Bowel Disease, Hyogo College of Medicine, 1-1, Mukogawacho, Nishinomiya, Hyogo, Japan

    Motoi Uchino & Hiroki Ikeuchi

  2. Department of Surgery, Toyonaka Municipal Hospital, Osaka, Japan

    Junzo Shimizu

  3. Department of Infectious Diseases, Hiroshima University Hospital, Hiroshima, Japan

    Hiroki Ohge

  4. Department of Surgery, Takatsuki General Hospital, Osaka, Japan

    Seiji Haji

  5. Department of Nursing, Surgical Science and Technology, Sapporo Medical University, Sapporo, Japan

    Toru Mizuguchi

  6. Department of Surgery, Mie Prefectural General Medical Center, Mie, Japan

    Yasuhiko Mohri

  7. Department of Anesthesiology and Critical Care Medicine, Fujita Health University School of Medicine, Aichi, Japan

    Chizuru Yamashita

  8. Department of Infection Control, National Center for Geriatrics and Gerontology, Aichi, Japan

    Yuichi Kitagawa

  9. Division of Infection Control and Prevention, University of Occupational and Environmental Health, Fukuoka, Japan

    Katsunori Suzuki

  10. Department of Anesthesiology and Resuscitology, Okayama University Hospital, Okayama, Japan

    Motomu Kobayashi

  11. Kitasato University School of Pharmacy, Tokyo, Japan

    Masahiro Kobayashi

  12. Infection Control Manager, QI Center, St. Luke’s International Hospital, Tokyo, Japan

    Fumie Sakamoto

  13. Hemodialysis and Surgery, International University of Health and Welfare Ichikawa Hospital, Chiba, Japan

    Masahiro Yoshida

  14. Department of Emergency Medicine, School of Medicine, University of Occupational and Environmental Health, Fukuoka, Japan

    Toshihiko Mayumi

  15. Department of Surgery, JR Sapporo Hospital, Sapporo, Japan

    Koichi Hirata

  16. Division of Infection Control and Prevention, Hyogo College of Medicine, Nishinomiya, Japan

    Yoshio Takesue

Authors
  1. Motoi Uchino
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hiroki Ikeuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Junzo Shimizu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hiroki Ohge
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Seiji Haji
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Toru Mizuguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yasuhiko Mohri
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Chizuru Yamashita
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yuichi Kitagawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Katsunori Suzuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Motomu Kobayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Masahiro Kobayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Fumie Sakamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Masahiro Yoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Toshihiko Mayumi
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Koichi Hirata
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Yoshio Takesue
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conception and design: MY, TM, and HI. Literature search: MK, TM, YM, and CY. Analysis and interpretation: MU and JS. Literature assessment and review: HO, SH, JS, YM, CY, YK, KS, MK, MK, FS, HI, and YT. Writing of the article: MU. Critical revision of the article: HI, YT, and KH. Final approval of the article: MU, TM, HO, SH, JS, YM, CY, YK, KS, MK, MK, FS, MY, TM, HI, YT, and KH.

Corresponding author

Correspondence to Motoi Uchino.

Ethics declarations

Conflicts of interest

This work was supported in part by the Japan Surgical Infection Society. We have no potential conflicts of interest to declare.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary file1 (XLSX 10 kb)

Supplementary file2 (XLSX 12 kb)

Supplementary file3 (XLSX 10 kb)

Supplementary file4 (XLSX 12 kb)

Supplementary file5 (XLSX 10 kb)

595_2020_2003_MOESM6_ESM.pptx

Supplemental Figure Funnel plot for the rate of incisional surgical site infection in patients undergoing surgery for A) ulcerative colitis and B) Crohn’s disease. Funnel plot for the rate of organ/space surgical site infection in patients undergoing surgery for C) ulcerative colitis and D) Crohn’s disease. The estimated effect measure is plotted on the x-axis, and the standard error is plotted on the y-axis (PPTX 57 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Uchino, M., Ikeuchi, H., Shimizu, J. et al. Association between preoperative tumor necrosis factor alpha inhibitor and surgical site infection after surgery for inflammatory bowel disease: a systematic review and meta-analysis. Surg Today 51, 32–43 (2021). https://doi.org/10.1007/s00595-020-02003-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00595-020-02003-9

Keywords

Search

Navigation