Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2022, 166(3):297-303 | DOI: 10.5507/bp.2021.050

Predictive value of tissue calprotectin for disease recurrence after ileocecal resection in pediatric Crohn's disease

Kristyna Zarubovaa, Ondrej Fabianb, c, d, Ondrej Hradskya, Tereza Lerchovaa, Filip Mikusd, Vojtech Dotlacile, Lucie Pose, Richard Skabae, Jiri Bronskya
a Gastroenterology and Nutrition Unit, Department of Paediatrics, 2nd Faculty of Medicine, Charles University and University Hospital Motol, V Uvalu 84, Prague 5, 150 06, Czech Republic
b Clinical and Transplant Pathology Centre, Institute for Clinical and Experimental Medicine, Videnska 1958/9, Prague 4, 140 21, Czech Republic
c Department of Pathology and Molecular Medicine, 3rd Faculty of Medicine, Charles University and Thomayer Hospital, Videnska 800, Prague 4, 140 59, Czech Republic
d Department of Pathology and Molecular Medicine, 2nd Faculty of Medicine, Charles University and University Hospital Motol, V Uvalu 84, Prague 5, 150 06, Czech Republic
e Department of Paediatric Surgery, 2nd Faculty of Medicine, Charles University and University Hospital Motol, V Uvalu 84, Prague 5, 150 06, Prague, Czech Republic

Aim: Detection of possible predictive factors of endoscopic recurrence after ileocecal resection in Crohn's disease could be very beneficial for the individual adjustment of postoperative therapy. The aim of this study was to verify, whether immunohistochemical detection of calprotectin in resection margins is useful in diagnostics of endoscopic recurrence.

Methods: In this study we included pediatric patients with Crohn's disease who underwent ileocecal resection, regardless of pre-operative or post-operative therapy (n=48). We collected laboratory, clinical, surgical, endoscopic and histopathological data at the time of surgery and at 6 months after surgery. The immunohistochemical staining of calprotectin antigen was performed on all paraffin blocks from the resection margins.

Results: Out of 48 patients 52% had endoscopic recurrence in the anastomosis (defined by Rutgeerts score) within 6 months after surgery. The number of cells positive for calprotectin in the proximal resection margin was negatively associated with recurrence (P=0.008), as was the elevated level of total calprotectin (from both resection margins). There was no correlation of calprotectin in distal resection margin and endoscopic recurrence. Fecal calprotectin over 100 ug/g (P=0.0005) and high CRP (P<0.001) at 6 months after ileocecal resection and peritonitis (P=0.048) were associated with endoscopic recurrence.

Conclusion: Approximately half of the patients developed endoscopic recurrence within 6 months after ileocecal resection. The predictive value of tissue calprotectin is questionable, as it is negatively associated with endoscopic recurrence. There are other potentially useful predictors, such as CRP and fecal calprotectin at 6 months after resection and the presence of peritonitis.

Keywords: calprotectin, Crohn's disease, pediatric, recurrence, prediction

Received: March 2, 2021; Revised: July 16, 2021; Accepted: July 19, 2021; Prepublished online: August 24, 2021; Published: September 14, 2022  Show citation

ACS AIP APA ASA Harvard Chicago IEEE ISO690 MLA NLM Turabian Vancouver
Zarubova, K., Fabian, O., Hradsky, O., Lerchova, T., Mikus, F., Dotlacil, V., ... Bronsky, J. (2022). Predictive value of tissue calprotectin for disease recurrence after ileocecal resection in pediatric Crohn's disease. Biomedical papers166(3), 297-303. doi: 10.5507/bp.2021.050
Download citation

References

  1. Bernell O, Lapidus A, Hellers G. Risk factors for surgery and postoperative recurrence in Crohn's disease. Ann Surg 2000;231:38-45. Go to original source... Go to PubMed...
  2. Peyrin-Biroulet L, Harmsen WS, Tremaine WJ, Zinsmeister AR, Sandborn WJ, Loftus EV, Jr. Surgery in a population-based cohort of Crohn's disease from Olmsted County, Minnesota (1970-2004). Am J Gastroenterol 2012;107:1693-701. Go to original source... Go to PubMed...
  3. De Cruz P, Kamm MA, Hamilton AL, Ritchie KJ, Krejany EO, Gorelik A, Liew D, Prideaux L, Lawrance IC, Andrews JM, Bampton PA, Gibson PR, Sparrow M, Leong RW, Florin TH, Gearry RB, Radford-Smith G, Macrae FA, Debinski H, Selby W, Kronborg I, Johnston MJ, Woods R, Elliott PR, Bell SJ, Brown SJ, Connell WR, Desmond PV. Crohn's disease management after intestinal resection: a randomised trial. Lancet 2015;385:1406-17. Go to original source... Go to PubMed...
  4. Buisson A, Chevaux JB, Allen PB, Bommelaer G, Peyrin-Biroulet L. Review article: the natural history of postoperative Crohn's disease recurrence. Aliment Pharmacol Ther 2012;35:625-33. Go to original source... Go to PubMed...
  5. Joustra V, Duijvestein M, Mookhoek A, Bemelman W, Buskens Ch, Koželj M, Novak G, Hindryckx P, Mostafavi N, DHaens G. Natural History and Risk Stratification of recurrent Crohn's disease after ileocolonic resection: A multicenter retrospective cohort study. Inflamm Bowel Dis 2021 Mar 30:izab044. Online ahead of print Go to original source... Go to PubMed...
  6. Baldassano RN, Han PD, Jeshion WC, Berlin JA, Piccoli DA, Lautenbach E, Mick R, Lichtenstein GR. Pediatric Crohn's disease: risk factors for postoperative recurrence. Am J gastroenterol 2001;96:2169-76. Go to original source... Go to PubMed...
  7. Pacilli M, Eaton S, Fell JM, Rawat D, Clarke S, Haddad MJ. Surgery in children with Crohn disease refractory to medical therapy. J Pediatr Gastr Nutr 2011;52:286-90. Go to original source... Go to PubMed...
  8. Zarubova K, Hradsky O, Copova I, Rouskova B, Pos L, Skaba R, Bronsky J. Endoscopic Recurrence 6 Months After Ileocecal Resection in Children With Crohn Disease Treated With Azathioprine. J Pediatr Gastr Nutr 2017;62:207-11. Go to original source... Go to PubMed...
  9. Qiu Y, Mao R, Chen BL, He Y, Zeng ZR, Xue L, Song XM, Li ZP, Chen MH. Fecal calprotectin for evaluating postoperative recurrence of Crohn's disease: a meta-analysis of prospective studies. Inflamm Bowel Dis 2015;21:315-22. Go to original source... Go to PubMed...
  10. Hukkinen M, Pakarinen MP, Merras-Salmio L, Koivusalo A, Rintala R, Kolho KL. Fecal calprotectin in the prediction of postoperative recurrence of Crohn's disease in children and adolescents. J Pediatr Surg 2016;51:1467-72. Go to original source... Go to PubMed...
  11. Fukunaga S, Kuwaki K, Mitsuyama K, Takedatsu H, Yoshioka S, Yamasaki H, Yamauchi R, Mori A, Kakuma T, Tsuruta O, Torimura T. Detection of calprotectin in inflammatory bowel disease: Fecal and serum levels and immunohistochemical localization. Int J Mol Med 2018;41:107-18. Go to original source... Go to PubMed...
  12. Guirgis M, Wendt E, Wang LM, Walsh A, Burger D, Bryant RV, Kent A, Adamson R, Brain O, Travis SPL, Keshav S. Beyond Histological Remission: Intramucosal Calprotectin as a Potential Predictor of Outcomes in Ulcerative Colitis. J Crohns Colitis 2017;11:460-70. Go to original source... Go to PubMed...
  13. Liu WB, Lu YM, Jin Z, Yang XL. Expression of calprotectin in colon mucosa and fecal of patients with ulcerative colitis. Beijing Da Xue Xue Bao Yi Xue Ban 2005;37:179-82.
  14. Ambe PC, Godde D, Bonicke L, Papadakis M, Storkel S, Zirngibl H. Calprotectin could be a potential biomarker for acute appendicitis. J Transl Med 2016;14:107. Go to original source... Go to PubMed...
  15. Misteli H, Koh CE, Wang LM, Mortensen NJ, George B, Guy R. Myenteric plexitis at the proximal resection margin is a predictive marker for surgical recurrence of ileocaecal Crohn's disease. Colorectal Dis 2015;17:304-10. Go to original source... Go to PubMed...
  16. Lemmens B, de Buck van Overstraeten A, Arijs I, Sagaert X, Van Assche G, Vermeire S, Tertychnyy A, Geboes K, Wolthuis S, D'Hoore A, de Herogh G, Ferrante M. Submucosal Plexitis as a Predictive Factor for Postoperative Endoscopic Recurrence in Patients with Crohn's Disease Undergoing a Resection with Ileocolonic Anastomosis: Results from a Prospective Single-centre Study. J Crohns Colitis 2017;11:212-20. Go to original source... Go to PubMed...
  17. Ferrante M, de Hertogh G, Hlavaty T, D'Haens G, Penninckx F, D'Hoore A, Vermiere S, Rutgeerts P, Geboes K, van Assche G. The value of myenteric plexitis to predict early postoperative Crohn's disease recurrence. Gastroenterology 2016;130:1595-606. Go to original source... Go to PubMed...
  18. Bressenot A, Peyrin-Biroulet L. Histologic features predicting postoperative Crohn's disease recurrence. Inflam Bowel Dis 2015;21:468-75. Go to original source... Go to PubMed...
  19. Simillis C, Jacovides M, Reese GE, Yamamoto T, Tekkis PP. Meta-analysis of the role of granulomas in the recurrence of Crohn disease. Dis Colon Rectum 2010;53:177-85. Go to original source... Go to PubMed...
  20. Li Y, Ge Y, Zhu W, Gong J, Cao L, Guo Z, Gu L, Li J. Increased enteric glial cells in proximal margin of resection is associated with postoperative recurrence of Crohn's disease. Journal of gastroenterology and hepatology 2018;33:638-44. Go to original source... Go to PubMed...
  21. Diederen K, de Ridder L, van Rheenen P, Wolters VM, Mearin ML, Damen GM, de Meij TG, van Wering H, Tseng LA, Oomen MW, de Jong JR, Sloots CE, Benninga MA, Kindermann A. Complications and Disease Recurrence After Primary Ileocecal Resection in Pediatric Crohn's Disease: A Multicenter Cohort Analysis. Inflam Bowel Dis 2017;23:272-82. Go to original source... Go to PubMed...
  22. Levine A, Koletzko S, Turner D, Escher JC, Cucchiara S, de Ridder L, Kolho KL, Veres G, Russell RK, Paerregaard A, Buderus S, Greer ML, Dias JA, Veereman-Wauters G, Lionetti P, Sladek M, Martin de Carpi J, Staiano A, Ruemmele FM, Wilson DC. ESPGHAN revised porto criteria for the diagnosis of inflammatory bowel disease in children and adolescents. J Pediatr Gastr Nutr 2014;58:795-806. Go to original source... Go to PubMed...
  23. Fabian O, Hradsky O, Potuznikova K, Kalfusova A, Krskova L, Hornofova L, Zamecnik J, Bronsky J. Low predictive value of histopathological scoring system for complications development in children with Crohn's disease. Pathol Res Pract 2017;213:353-8. Go to original source... Go to PubMed...
  24. Rutgeerts P, Geboes K, Vantrappen G, Beyls J, Kerremans R, Hiele M. Predictability of the postoperative course of Crohn's disease. Gastroenterology 1990;99:956-63. Go to original source... Go to PubMed...
  25. Ledder O, Church P, Cytter-Kuint R, Martinez-Leon M, Sladek M, Coppenrath E, Weiss B, Yerushalmi B, de Carpi JM, Duchano L, Towbin A, Assa A, Shaoul R, Mearin ML, Alex G, Griffiths A, Turner D. A Simple Endoscopic Score Modified for the Upper Gastrointestinal tract in Crohn's Disease (UGI-SES-CD): a report from the ImageKids study. J Crohns Colitis 2018;12:1073-8. Go to original source... Go to PubMed...
  26. Bobanga ID, Bai S, Swanson MA, Champagne BJ, Reynolds HJ, Delaney CP, Barksdale EM Jr, Stein SL. Factors influencing disease recurrence after ileocolic resection in adult and pediatric onset Crohn's disease. Am J Surg 2014;208:591-6. Go to original source... Go to PubMed...
  27. Kotze PG, Yamamoto T, Danese S, Suzuki Y, Teixeira FV, de Albuquerque IC, Saad-Hossne R, de Barcelos IF, da Silva RN, da Silva Kotze LM, Olandoski M, Sacchi M, Yamada A, Takeuchi K, Spinelli A. Direct retrospective comparison of adalimumab and infliximab in preventing early postoperative endoscopic recurrence after ileocaecal resection for crohn's disease: results from the MULTIPER database. J Crohns Colitis 2015;9:541-7. Go to original source... Go to PubMed...
  28. Auzolle C, Nancey S, Tran-Minh ML, Buisson A. Male gender, active smoking and previous intestinal resection are risk factors for post-operative endoscopic recurrence in Crohn's disease: results from a prospective cohort study. Aliment Pharmacol Ther 2018;48:924-32. Go to original source... Go to PubMed...
  29. Amil-Dias J, Kolacek S, Turner D, Paerregaard A, Rintala R, Afzal NA, Karolewska-Bochenek K, Bronsky J, Chong S, Fell J, Hojsak I, Hugot JP, Koletzko S, Kumar D, Lazowska-Przeorek I, Lillehei C, Lionetti P, Martin-de-Carpi J, Pakarinen M, Ruemmele FM, Shaoul R, Spray C, Staiano A, Sugarman I, Wilson DC, Winter H, Kolho KL. Surgical Management of Crohn Disease in Children: Guidelines From the Paediatric IBD Porto Group of ESPGHAN. J Pediatr Gastr Nutr 2017;64:818-35. Go to original source... Go to PubMed...
  30. Wright EK, Kamm MA, De Cruz P, Hamilton AL, Ritchie KJ, Krejany EO, Leach S, Gorelik A, Liew D, Prideaux L, Lawrance IC, Andrews JM, Bampton PA, Jakobovits SL, Florin TH, Gibson PR, Debinski H, Macrae FA, Samuel D, Kronborg I, Radford-Smith G, Selby W, Johnston MJ, Woods R, Elliott PR, Bell SJ, Brown SJ, Connell WR, Day AS, Desmond PV, Gearry RB.. Measurement of fecal calprotectin improves monitoring and detection of recurrence of Crohn's disease after surgery. Gastroenterology 2015;148:938-41.e1. Go to original source... Go to PubMed...
  31. Tham YS, Yung DE, Fay S, Yamamoto T. Fecal calprotectin for detection of postoperative endoscopic recurrence in Crohn's disease: systematic review and meta-analysis. Therap Adv Gastroenterol 2018;11:1756284818785571. Go to original source... Go to PubMed...
  32. Karas PL, Goh SL, Dhital K. Is low serum albumin associated with postoperative complications in patients undergoing cardiac surgery? Interact Cardiov Th 2015;21:777-86. Go to original source... Go to PubMed...
  33. Kamath AF, Nelson CL, Elkassabany N, Guo Z, Liu J. Low Albumin Is a Risk Factor for Complications after Revision Total Knee Arthroplasty. J Knee Surg 2017;30:269-75. Go to original source... Go to PubMed...
  34. Galata C, Kienle P, Weiss C, Seyfried S, Reissfelder C, Hardt J. Risk factors for early postoperative complications in patients with Crohn's disease after colorectal surgery other than ileocecal resection or right hemicolectomy. Int J Colorectal Dis 2019;34:293-300. Go to original source... Go to PubMed...
  35. Huang W, Tang Y, Nong L, Sun Y. Risk factors for postoperative intra-abdominal septic complications after surgery in Crohn's disease: A meta-analysis of observational studies. J Crohns Colitis 2015;9:293-301. Go to original source... Go to PubMed...

This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC BY 4.0), which permits use, distribution, and reproduction in any medium, provided the original publication is properly cited. No use, distribution or reproduction is permitted which does not comply with these terms.