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Effect of ulcerative colitis duration on the usefulness of immunochemical fecal occult blood test result as a disease activity biomarker

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Abstract

Purpose

The effects of ulcerative colitis (UC) duration on biomarker accuracy are unknown. We investigated the effects of UC duration on the predictive accuracy of biomarkers including immunochemical fecal occult blood test (FOBT, also known as FIT), prostaglandin E-major urinary metabolite (PGE-MUM), and C-reactive protein (CRP).

Methods

We divided 133 samples into groups based on disease duration. Clinical and endoscopic remission was defined as Lichtiger’s clinical activity index (CAI) of ≤ 4, Mayo endoscopic subscore (MES) of 0, and UC endoscopic index of severity (UCEIS) of ≤ 1.

Results

FIT results were significantly correlated with all activity scores when the disease duration was < 4 years. When the disease duration was ≥ 4 years, FIT results were significantly correlated with the CAI and MES but not with UCEIS. When the disease duration was ≥ 5 years, FIT and CAI were significantly correlated, whereas FIT and MES or FIT and UCEIS did not show any correlation. When the duration was ≥ 4 years, PGE-MUM and CRP showed a significant correlation with CAI, MES, and UCEIS. Receiver operating characteristic curve analysis of biomarker data for predicting endoscopic remission showed that the accuracy of FIT was superior to that of PGE-MUM and CRP in the < 4-year group.

Conclusions

FIT is an accurate biomarker reflecting the endoscopic score until 4 years in patients with UC. However, owing to the increased number of false negatives, the usefulness of FIT may decline after 4 years. Hence, evaluation of UC in combination with other biomarkers is recommended.

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References

  1. Podolsky DK (2002) Inflammatory bowel disease. N Engl J Med 347:417–429. https://doi.org/10.1056/NEJMra020831

    Article  CAS  PubMed  Google Scholar 

  2. Colombel JF, Rutgeerts P, Reinisch W, Esser D, Wang Y, Lang Y, Marano CW, Strauss R, Oddens BJ, Feagan BG, Hanauer SB, Lichtenstein GR, Present D, Sands BE, Sandborn WJ (2011) Early mucosal healing with infliximab is associated with improved long-term clinical outcomes in ulcerative colitis. Gastroenterology 141:1194–1201. https://doi.org/10.1053/j.gastro.2011.06.054

    Article  CAS  PubMed  Google Scholar 

  3. Vermeire S, Van Assche G, Rutgeerts et al (2004) C-Reactive protein as a marker for inflammatory bowel disease. Inflamm Bowel Dis 10:661–665. https://doi.org/10.1097/00054725-200409000-00026

    Article  PubMed  Google Scholar 

  4. Sands BE (2015) Biomarkers of inflammation in inflammatory bowel disease. Gastroenterology 149:1275–1285. https://doi.org/10.1053/j.gastro.2015.07.003

    Article  CAS  PubMed  Google Scholar 

  5. Schoepfer AM, Beglinger C, Straumann A, Trummler M, Renzulli P, Seibold F (2009) Ulcerative colitis: correlation of the Rachmilewitz endoscopic activity index with fecal calprotectin, clinical activity, C-reactive protein, and blood leukocytes. Inflamm Bowel Dis 15:1851–1858. https://doi.org/10.1002/ibd.20986

    Article  PubMed  Google Scholar 

  6. D’Haens G, Ferrante M, Vermeire S et al (2012) Fecal calprotectin is a surrogate marker for endoscopic lesions in inflammatory bowel disease. Inflamm Bowel Dis 18:2218–2224. https://doi.org/10.1002/ibd.22917

    Article  PubMed  Google Scholar 

  7. Nakarai A, Kato J, Hiraoka S, Kuriyama M, Akita M, Hirakawa T, Okada H, Yamamoto K (2013) Evaluation of mucosal healing of ulcerative colitis by a quantitative fecal immunochemical test. Am J Gastroenterol 108:83–89. https://doi.org/10.1038/ajg.2012.315

    Article  CAS  PubMed  Google Scholar 

  8. Takashima S, Kato J, Hiraoka S, Nakarai A, Takei D, Inokuchi T, Sugihara Y, Takahara M, Harada K, Okada H, Tanaka T, Yamamoto K (2015) Evaluation of mucosal healing in ulcerative colitis by fecal calprotectin vs. fecal immunochemical test. Am J Gastroenterol 110:873–880. https://doi.org/10.1038/ajg.2015.66

    Article  PubMed  Google Scholar 

  9. Kato J, Hiraoka S, Nakarai A, Takashima S, Inokuchi T, Ichinose M (2016) Fecal immunochemical test as a biomarker for inflammatory bowel diseases: can it rival fecal calprotectin? Intest Res 14:5–14. https://doi.org/10.5217/ir.2016.14.1.5

    Article  PubMed  PubMed Central  Google Scholar 

  10. Arai Y, Matsuura T, Matsuura et al (2016) Prostaglandin E-major urinary metabolite as a biomarker for inflammation in ulcerative colitis: prostaglandins revisited. Digestion 93:32-39. https://doi.org/10.1159/000441665

  11. Hagiwara S, Okayasu I, Fujiwara M, Matsuura M, Ohnishi H, Ito S, Kishimoto H, Nambu R, Kagimoto S (2017) Prostaglandin E-major urinary metabolite as a biomarker for pediatric ulcerative colitis activity. J Pediatr Gastroenterol Nutr 64:955–961. https://doi.org/10.1097/MPG.0000000000001477

    Article  CAS  PubMed  Google Scholar 

  12. Langholz E, Munkholm P, Davidsen M, Binder V (1994) Course of ulcerative colitis: analysis of changes in disease activity over years. Gastroenterology 107:3–11. https://doi.org/10.1016/0016-5085(94)90054-x

    Article  CAS  PubMed  Google Scholar 

  13. Okayasu I, Ohnishi H, Sarandi I, Shojima J, Komatsu J, Oritsu M, Sasabe M, Nanami KO, Matsuura M, Azumi JI, Ito S, Fujiwara M (2014) Significant increase of prostaglandin E major urinary metabolite in male smokers: a screening study of age and gender differences using a simple radioimmunoassay. J Clin Lab Anal 28:32–41. https://doi.org/10.1002/jcla.21640

    Article  CAS  PubMed  Google Scholar 

  14. Horikiri T, Hara H, Saito N, Araya J, Takasaka N, Utsumi H, Yanagisawa H, Hashimoto M, Yoshii Y, Wakui H, Minagawa S, Ishikawa T, Shimizu K, Numata T, Arihiro S, Kaneko Y, Nakayama K, Matsuura T, Matsuura M, Fujiwara M, Okayasu I, Ito S, Kuwano K (2017) Increased levels of prostaglandin E major urinary metabolite (PGE MUM) in chronic fibrosing interstitial pneumonia. Respir Med 122:43–50. https://doi.org/10.1016/j.rmed.2016.11.017

    Article  PubMed  Google Scholar 

  15. Lichtiger S, Present DH (1990) Preliminary report: cyclosporin in treatment of severe active ulcerative colitis. Lancet 336:16–19. https://doi.org/10.1016/0140-6736(90)91521-b

    Article  CAS  PubMed  Google Scholar 

  16. Schroeder KW, Tremaine WJ, Ilstrup DM (1987) Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med 317:1625–1629. https://doi.org/10.1056/NEJM198712243172603

    Article  CAS  PubMed  Google Scholar 

  17. Dhaens G, Sandborn WJ, Feagan BG et al (2007) A review of activity indices and efficacy end points for clinical trials of medical therapy in adults with ulcerative colitis. Gastroenterology 132:763–786. https://doi.org/10.1053/j.gastro.2006.12.038

    Article  CAS  Google Scholar 

  18. Raab Y, Sundberg C, Hällgren R, Knutson L, Gerdin B (1995) Mucosal synthesis and release of prostaglandin E2 from activated eosinophils and macrophages in ulcerative colitis. Am J Gastroenterol 90:614–620

    CAS  PubMed  Google Scholar 

  19. Nakarai A, Kato J, Hiraoka S, Takashima S, Takei D, Inokuchi T, Sugihara Y, Takahara M, Harada K, Okada H (2016) Ulcerative colitis patients in clinical remission demonstrate correlations between fecal immunochemical test results, mucosal healing, and risk of relapse. World J Gastroenterol 22:5079–5087. https://doi.org/10.3748/wjg.v22.i21.5079

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Hiraoka S, Kato J, Nakarai A, Takashima S, Inokuchi T, Takei D, Sugihara Y, Takahara M, Harada K, Okada H (2016) Consecutive measurements by faecal immunochemical test in quiescent ulcerative colitis patients can detect clinical relapse. J Crohns Colitis 10:687–694. https://doi.org/10.1093/ecco-jcc/jjw025

    Article  PubMed  Google Scholar 

  21. Arai Y, Arihiro S, Matsuura T, Kato T, Matsuoka M, Saruta M, Mitsunaga M, Matsuura M, Fujiwara M, Okayasu I, Ito S, Tajiri H (2014) Prostaglandin E-major urinary metabolite as a reliable surrogate marker for mucosal inflammation in ulcerative colitis. Inflamm Bowel Dis 20:1208–1216. https://doi.org/10.1097/MIB.0000000000000062

    Article  PubMed  Google Scholar 

  22. Johnson JC, Schmidt CR, Shrubsole MJ, Billheimer DD, Joshi PR, Morrow JD, Heslin MJ, Washington MK, Ness RM, Zheng W, Schwartz DA, Coffey RJ, Beauchamp RD, Merchant NB (2006) Urine PGE M: a metabolite of prostaglandin E2 as a potential biomarker of advanced colorectal neoplasia. Clin Gastroenterol Hepatol 4:1358–1365. https://doi.org/10.1016/j.cgh.2006.07.015

    Article  CAS  PubMed  Google Scholar 

  23. Cai Q, Gao YT, Chow WH, Shu XO, Yang G, Ji BT, Wen W, Rothman N, Li HL, Morrow JD, Zheng W (2006) Prospective study of urinary prostaglandin E2 metabolite and colorectal cancer risk. J Clin Oncol 24:5010–5016. https://doi.org/10.1200/JCO.2006.06.4931

    Article  CAS  PubMed  Google Scholar 

  24. Csiki I, Morrow JD, Sandler A et al (2005) Targeting cyclooxygenase-2 in recurrent non-small cell lung cancer: a phase II trial of celecoxib and docetaxel. Clin Cancer Res l5:6634–6640. https://doi.org/10.1158/1078-0432.CCR-05-0436

    Article  CAS  Google Scholar 

  25. Kim S, Taylor JA, Milne GL, Sandler DP (2013) Association between urinary prostaglandin E2 metabolite and breast cancer risk: a prospective, case cohort study of postmenopausal women. Cancer Prev Res (Phil) 6:511–528. https://doi.org/10.1158/1940-6207.CAPR-13-0040

    Article  CAS  Google Scholar 

  26. Zhao J, Wang J, Du J et al (2015) Urinary prostaglandin E2 metabolite and pancreatic cancer risk: case control study in urban Shanghai. PLoS One 10:1–10. https://doi.org/10.1371/journal.pone.0118004

    Article  CAS  Google Scholar 

  27. Eder P, Stawczyk-Eder K, Łykowska-Szuber L, Krela-Kaźmierczak I, Klimczak K, Szymczak A, Szachta P, Linke K (2014) Association between disease duration and usefulness of fecal calprotectin measurement in patients with Crohn’s disease. Pol Arch Med Wewn 124:51–57

    PubMed  Google Scholar 

  28. Tibble JA, Sigthorsson G, Bridger S, Fagerhol MK, Bjarnason I (2000) Surrogate markers of intestinal inflammation are predictive of relapse in patients with inflammatory bowel disease. Gastroenterology 119:15–22. https://doi.org/10.1053/gast.2000.8523

    Article  CAS  PubMed  Google Scholar 

  29. Costa F, Mumolo MG, Ceccarelli L, Bellini M, Romano MR, Sterpi C, Ricchiuti A, Marchi S, Bottai M (2005) Calprotectin is a stronger predictive marker of relapse in ulcerative colitis than in Crohn’s disease. Gut 54:364–368. https://doi.org/10.1136/gut.2004.043406

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. D’Incà R, Dal Pont E, Di Leo V et al (2008) Can calprotectin predict relapse risk in inflammatory bowel disease? Am J Gastroenterol 103:2007–2014. https://doi.org/10.1111/j.1572-0241.2008.01870.x

    Article  CAS  PubMed  Google Scholar 

  31. Lobatón T, Rodríguez-Moranta F, Lopez A, Sánchez E, Rodríguez-Alonso L, Guardiola J (2013) A new rapid quantitative test for faecal calprotectin predicts endoscopic activity in ulcerative colitis. Inflamm Bowel Dis 19:1034–1042. https://doi.org/10.1097/MIB.0b013e3182802b6e

    Article  PubMed  Google Scholar 

  32. Yamaguchi S, Takeuchi Y, Arai K, Fukuda K, Kuroki Y, Asonuma K, Takahashi H, Saruta M, Yoshida H (2016) Faecal calprotectin is a clinically relevant biomarker of mucosal healing in patients with quiescent ulcerative colitis. J Gastroenterol Hepatol 31:93–98. https://doi.org/10.1111/jgh.13061

    Article  CAS  PubMed  Google Scholar 

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Funding

This work was funded by a Grant-in-Aid for Scientific Research (C) (no. 18K07908) from the Japanese Ministry of Education, Culture, Sports, Science, and Technology.

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Authors and Affiliations

  1. First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan

    Natsuki Ishida, Takahiro Miyazu, Tomoharu Matsuura, Ryosuke Takano, Satoshi Tamura, Takuma Kagami, Mihoko Yamade, Yasushi Hamaya & Ken Sugimoto

  2. Department of Endoscopic and Photodynamic Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan

    Shinya Tani & Satoshi Osawa

  3. Department of Laboratory Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizusoka, Japan

    Moriya Iwaizumi

  4. Center for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan

    Takahisa Furuta

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  1. Natsuki Ishida
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Contributions

N.I. and K.S. designed the study. Ta.M., To.M., R.T., Sa.T., and T.K. collected the data. Sh.T., M.Y., M.I., and Y.H. analyzed the data. N.I. and K.S. wrote the paper. S.O. and T.F. provided critical insight regarding paper preparation

Corresponding author

Correspondence to Ken Sugimoto.

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This study was reviewed and approved by the Institutional Review Board of Hamamatsu University School of Medicine.

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Ishida, N., Miyazu, T., Matsuura, T. et al. Effect of ulcerative colitis duration on the usefulness of immunochemical fecal occult blood test result as a disease activity biomarker. Int J Colorectal Dis 35, 1729–1739 (2020). https://doi.org/10.1007/s00384-020-03636-5

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