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Noninvasive evaluation of mucosal healing in inflammatory bowel diseases

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Abstract

Current opinions increasingly cite the need to achieve not only clinical response but also endoscopic mucosal healing in the treatment of both types of inflammatory bowel disease: ulcerative colitis (UC) and Crohn’s disease (CD). Although endoscopic procedures are necessary for confirmation of mucosal healing, undergoing colonoscopy is invasive and burdensome to patients. Therefore, alternative noninvasive methods of evaluating or predicting mucosal status have been eagerly desired. For this purpose, blood, fecal, and radiologic modalities have been suggested and examined. C-reactive protein and fecal markers such as fecal calprotectin can evaluate active inflammation to some extent in both UC and CD. However, their predictive values for mucosal healing have not yet been fully evaluated and current knowledge indicates that the values were rather insufficient. Radiologic modalities such as computed tomography, magnetic resonance, and ultrasound can also evaluate mucosal inflammation but are currently not suitable for detection of healing. Capsule endoscopy may be optimal for evaluating mucosal status of the small bowel in CD patients, but sufficient data are not yet available, particularly for mucosal healing. Thus, these candidates for the surrogate modality are currently imperfect for evaluation of mucosal healing, but the changes in values/findings of these modalities after initiation of therapy appear to be rather promising as a marker of efficacy of the therapy. Finally, our recent data showed that a fecal immunochemical test for evaluation of mucosal healing in UC was very promising and this method should be further evaluated in CD also.

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References

  1. Cellier C, Sahmoud T, Froguel E, Adenis A, Belaiche J, Bretagne JF, et al. Correlations between clinical activity, endoscopic severity, and biological parameters in colonic or ileocolonic Crohn’s disease: A prospective multicentre study of 121 cases. Gut. 1994;35:231–5.

    Article  PubMed  CAS  Google Scholar 

  2. Solem CA, Loftus EV Jr, Tremaine WJ, Harmsen WS, Zinsmeister AR, Sandborn WJ. Correlation of C-reactive protein with clinical, endoscopic, histologic, and radiographic activity in inflammatory bowel disease. Inflamm Bowel Dis. 2005;11:707–12.

    Article  PubMed  Google Scholar 

  3. Sandborn WJ, Feagan BG, Hanauer S, Lochs H, Löfberg R, Modigliani R, et al. A review of activity indices and efficacy endopoints for clinical trials of medical therapy in adults with Crohn’s disease. Gastroenterology. 2002;122:512–30.

    Article  PubMed  Google Scholar 

  4. Lichtiger S, Present DH, Kornbluth A, Gelernt I, Bauer J, Galler G, et al. Cyclosporine in severe ulcerative colitis refractory to steroid therapy. N Engl J Med. 1994;330:1841–5.

    Article  PubMed  CAS  Google Scholar 

  5. Irvine E. Usual therapy improves perianal Crohn’s disease as measured by a new disease activity index. McMaster IBD study group. J Clin Gastroenterol. 1995;20:27–32.

    Article  PubMed  CAS  Google Scholar 

  6. Present DH, Rutgeerts P, Targan S, Hanauer SB, Mayer L, van Hogezand RA, et al. Infliximab for the treatment of fistulas in patients with Crohn’s disease. N Engl J Med. 1999;340:1398–405.

    Article  PubMed  CAS  Google Scholar 

  7. Pineton de Chambrun G, Peyrin-Biroulet L, Lemann M, Colombel JF. Clinical implications of mucosal healing for the management of IBD. Nat Rev Gastroenterol Hepatol. 2010;7:15–29.

    Article  PubMed  Google Scholar 

  8. Colombel JF, Rutgeerts P, Reinisch W, Esser D, Wang Y, Lang Y, et al. Early mucosal healing with infliximab is associated with improved long-term clinical outcomes in ulcerative colitis. Gastroenterology. 2011;141:1194–201.

    Article  PubMed  CAS  Google Scholar 

  9. Ardizzone S, Cassinotti A, Duca P, Mazzali C, Penati C, Manes G, et al. Mucosal healing predicts late outcomes after the first course of corticosteroids for newly diagnosed ulcerative colitis. Clin Gastroenterol Hepatol. 2011;9:483–9.

    Article  PubMed  Google Scholar 

  10. Baert F, Moortgat L, Van Assche G, Caenepeel P, Vergauwe P, De Vos M, et al. Mucosal healing predicts sustained clinical remission in patients with early-stage Crohn’s disease. Gastroenterology. 2010;138:463–8.

    Article  PubMed  Google Scholar 

  11. Daperno M, D’Haens G, Van Assche G, Baert F, Bulois P, Maunoury V, et al. Development and validation of a new, simplified endoscopic activity score for Crohn’s disease: the SES-CD. Gastrointest Endosc. 2004;60:505–12.

    Article  PubMed  Google Scholar 

  12. Rutgeerts P, Diamond RH, Bala M, Olson A, Lichtenstein GR, Bao W, et al. Scheduled maintenance treatment with infliximab is superior to episodic treatment for the healing of mucosal ulceration associated with Crohn’s disease. Gastrointestinal Endosc. 2006;63:433–42.

    Article  Google Scholar 

  13. Schnitzler F, Fidder H, Ferrante M, Noman M, Arijs I, Van Assche G, et al. Mucosal healing predicts long-term outcome of maintenance therapy with infliximab in Crohn’s disease. Inflamm Bowel Dis. 2009;15:1295–301.

    Article  PubMed  Google Scholar 

  14. Frøslie KF, Jahnsen J, Moum BA, Vatn MH, IBSEN Group. Mucosal healing in inflammatory bowel disease: results from a Norwegian population-based cohort. Gastroenterology. 2007;133:412–22.

    Article  PubMed  Google Scholar 

  15. Rutgeers P, Vermeire S, Van Assche G. Mucosal healing in inflammatory bowel disease: impossible ideal or therapeutic target? Gut. 2007;56:453–5.

    Article  Google Scholar 

  16. D’Haens GR, Fedorak R, Lémann M, Feagan BG, Kamm MA, Cosnes J, et al. Endpoints for clinical trials evaluating disease modification and structural damage in adults with Crohn’s disease. Inflamm Bowel Dis. 2009;15:1599–604.

    Article  PubMed  Google Scholar 

  17. Menees S, Higgins P, Korsnes S, Elta G. Does colonoscopy cause increased ulcerative colitis symptoms? Inflamm Bowel Dis. 2007;13:12–8.

    Article  PubMed  Google Scholar 

  18. Vermeire S, Van Assche G, Rutgeerts P. Laboratory markers in IBD: useful, magic, or unnecessary toys? Gut. 2006;55:426–31.

    Article  PubMed  CAS  Google Scholar 

  19. Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med. 1987;317:1625–9.

    Article  PubMed  CAS  Google Scholar 

  20. Sipponen T, Savilahti E, Kolho KL, Nuutinen H, Turunen U, Färkkilä M. Crohn’s disease activity assessed by fecal calprotectin and lactoferrin: correlation with Crohn’s disease activity index and endoscopic findings. Inflamm Bowel Dis. 2008;14:40–6.

    Article  PubMed  Google Scholar 

  21. Schoepfer AM, Beglinger C, Staumann A, Trummler M, Vavricka SR, Bruegger LE, et al. Fecal calprotectin correlates more closely with the simple endoscopic score for Crohn’s disease (SES-CD) than CRP, blood leukocytes, and the CDAI. Am J Gastroenterol. 2010;105:162–9.

    Article  PubMed  CAS  Google Scholar 

  22. Mary JY, Modigliani R. Development and validation of an endoscopic index of the severity for Crohn’s disease: a prospective multicentre study. Groupe d’Etudes Thérapeutiques des Affections Inflammatoires du Tube Digestif (GETAID). Gut. 1989;30:983–9.

    Article  PubMed  CAS  Google Scholar 

  23. Kiss LS, Szamosi T, Molnar T, Miheller P, Lakatos L, Vincze A, et al. Early clinical remission and normalisation of CRP are the strongest predictors of efficacy, mucosal healing and dose escalation during the first year of adalimumab therapy in Crohn’s disease. Aliment Pharmacol Ther. 2011;34:911–22.

    Article  PubMed  CAS  Google Scholar 

  24. Jürgens M, Mahachie John JM, Cleynen I, Schnitzler F, Fidder H, van Moerkercke W, et al. Levels of C-reactive protein are associated with response to infliximab therapy in patients with Crohn’s disease. Clin Gastroenterol Hepatol. 2011;9:421–7.

    Article  PubMed  Google Scholar 

  25. Rachmilewitz D. Coated mesalazine (5-aminosalicylic acid) versus sulphasalazine in the treatment of active ulcerative colitis: a randomised trial. Br Med J. 1989;298:82–6.

    Article  CAS  Google Scholar 

  26. Schoepfer AM, Beglinger C, Straumann A, Trummler M, Renzulli P, Seibold F. Ulcerative colitis: correlation of the Rachmilewitz endoscopic activity index with fecal calprotectin, clinical activity, C-reactive protein, and blood leukocytes. Inflamm Bowel Dis. 2009;15:1851–8.

    Article  PubMed  Google Scholar 

  27. D’Haens G, Ferrante M, Vermeire S, Baert F, Noman M, Moortgat L, et al. Fecal calprotectin is a surrogate marker for endoscopic lesions in inflammatory bowel disease. Inflamm Bowel Dis 2012;18:2218–24.

    Google Scholar 

  28. Langhorst J, Elsenbruch S, Koelzer J, Rueffer A, Michalsen A, Dobos GJ. Noninvasive markers in the assessment of intestinal inflammation in inflammatory bowel diseases: performance of fecal lactoferrin, calprotectin, and PMN-elastase, CRP, and clinical indices. Am J Gastroenterol. 2008;103:162–9.

    Article  PubMed  Google Scholar 

  29. Sipponen T, Savilahti E, Kärkkäinen P, Kolho KL, Nuutinen H, Turunen U, et al. Fecal calprotectin, lactoferrin, and endoscopic disease activity in monitoring anti-TNF-alpha therapy for Crohn’s disease. Inflamm Bowel Dis. 2008;14:1392–8.

    Article  PubMed  Google Scholar 

  30. Nakarai A, Kato J, Hiraoka S, Kuriyama M, Akita M, Hirakawa T, et al. Evaluation of mucosal healing of ulcerative colitis by a quantitative fecal immunochemical test. Am J Gastroenterol; 2012. doi:10.1038/ajg.2012.315.

  31. Fletcher JG, Fidler JL, Bruining DH, Huprich JE. New concepts in intestinal imaging for inflammatory bowel diseases. Gastroenterology. 2011;140:1795–806.

    Article  PubMed  Google Scholar 

  32. Doherty GA, Moss AC, Cheifetz AS. Capsule endoscopy for small-bowel evaluation in Crohn’s disease. Gastrointest Endosc. 2011;74:167–75.

    Article  PubMed  Google Scholar 

  33. Murphy SJ, Kronbluth A. Double balloon enteroscopy in Crohn’s disease: where are we now and where should we go? Inflamm Bowel Dis. 2011;17:485–90.

    Article  PubMed  Google Scholar 

  34. Siddiki H, Fletcher JG, Hara AK, Kofler JM, McCollough CH, Fidler JL, et al. Validation of a lower radiation computed tomography enterography imaging protocol to detect Crohn’s disease in the small bowel. Inflamm Bowel Dis. 2011;17:778–86.

    Article  PubMed  Google Scholar 

  35. Lee SJ, Park SH, Kim AY, Yang SK, Yun SC, Lee SS, et al. A prospective comparison of standard-dose CT enterography and 50% reduced-dose CT enterography with and without noise reduction for evaluating Crohn disease. Am J Roentgenol. 2011;197:50–7.

    Article  Google Scholar 

  36. Lee SS, Kim AY, Yang SK, Chung JW, Kim SY, Park SH, et al. Crohn disease of the small bowel: comparison of CT enterography, MR enterography, and small-bowel follow-through as diagnostic techniques. Radiology. 2009;251:751–61.

    Article  PubMed  Google Scholar 

  37. Siddiki HA, Fidler JL, Fletcher JG, Burton SS, Huprich JE, Hough DM, et al. Prospective comparison of state-of-the-art MR enterography and CT enterography in small-bowel Crohn’s disease. Am J Roentgenol. 2009;193:113–21.

    Article  Google Scholar 

  38. Booya F, Fletcher JG, Huprich JE, Barlow JM, Johnson CD, Fidler JL, et al. Active Crohn disease: CT findings and interobserver agreement for enteric phase CT enterography. Radiology. 2006;241:787–95.

    Article  PubMed  Google Scholar 

  39. Solem CA, Loftus EV Jr, Fletcher JG, Baron TH, Gostout CJ, Petersen BT, et al. Small-bowel imaging in Crohn’s disease: a prospective, blinded, 4-way comparison trial. Gastrointest Endosc. 2008;68:255–66.

    Article  PubMed  Google Scholar 

  40. Masselli G, Casciani E, Polettini E, Gualdi G. Comparison of MR enteroclysis with MR enterography and conventional enteroclysis in patients with Crohn’s disease. Eur Radiol. 2008;18:438–47.

    Article  PubMed  Google Scholar 

  41. Parente F, Greco S, Molteni M, Cucino C, Maconi G, Sampietro GM, et al. Role of early ultrasound in detecting inflammatory intestinal disorders and identifying their anatomical location within the bowel. Aliment Pharmacol Ther. 2003;18:1009–16.

    Article  PubMed  CAS  Google Scholar 

  42. Tarján Z, Tóth G, Györke T, Mester A, Karlinger K, Makó EK. Ultrasound in Crohn’s disease of the small bowel. Eur J Radiol. 2000;35:176–82.

    Article  PubMed  Google Scholar 

  43. Ruess L, Blask AR, Bulas DI, Mohan P, Bader A, Latimer JS, et al. Inflammatory bowel disease in children and young adults: correlation of sonographic and clinical parameters during treatment. Am J Roentgenol. 2000;175:79–84.

    CAS  Google Scholar 

  44. Byrne MF, Farrell MA, Abass S, Fitzgerald A, Varghese JC, Thornton F, et al. Assessment of Crohn’s disease activity by Doppler sonography of the superior mesenteric artery, clinical evaluation and the Crohn’s disease activity index: a prospective study. Clin Radiol. 2001;56:973–8.

    Article  PubMed  CAS  Google Scholar 

  45. Parente F, Molteni M, Marino B, Colli A, Ardizzone S, Greco S, et al. Are colonoscopy and bowel ultrasound useful for assessing response to short-term therapy and predicting disease outcome of moderate-to-severe forms of ulcerative colitis? a prospective study. Am J Gastroenterol. 2010;105:1150–7.

    Article  PubMed  Google Scholar 

  46. Bruining DH, Loftus EV Jr, Ehman EC, Siddiki HA, Nguyen DL, Fidler JL, et al. Computed tomography enterography detects intestinal wall changes and effects of treatment in patients with Crohn’s disease. Clin Gastroenterol Hepatol. 2011;9:679–83.

    Article  PubMed  Google Scholar 

  47. Sempere GA, Martinez Sanjuan V, Medina Chulia E, Benages A, Tome Toyosato A, Canelles P, et al. MRI evaluation of inflammatory activity in Crohn’s disease. Am J Roentgenol. 2005;184:1829–35.

    Google Scholar 

  48. Paredes JM, Ripollés T, Cortés X, Martínez MJ, Barrachina M, Gómez F, et al. Abdominal sonographic changes after antibody to tumor necrosis factor (anti-TNF) alpha therapy in Crohn’s Disease. Dig Dis Sci. 2010;55:404–10.

    Article  PubMed  CAS  Google Scholar 

  49. Petruzziello C, Calabrese E, Onali S, Zuzzi S, Condino G, Ascolani M, et al. Small bowel capsule endoscopy vs conventional techniques in patients with symptoms highly compatible with Crohn’s disease. J Crohns Colitis. 2011;5:139–47.

    Article  PubMed  Google Scholar 

  50. Costamagna G, Shah SK, Riccioni ME, Foschia F, Mutignani M, Perri V, et al. A prospective trial comparing small bowel radiographs and video capsule endoscopy for suspected small bowel disease. Gastroenterology. 2002;123:999–1005.

    Article  PubMed  Google Scholar 

  51. Dionisio PM, Gurudu SR, Leighton JA, Leontiadis GI, Fleischer DE, Hara AK, et al. Capsule endoscopy has a significantly higher diagnostic yield in patients with suspected and established small-bowel Crohn’s disease: a meta-analysis. Am J Gastroenterol. 2010;105:1240–8.

    Article  PubMed  Google Scholar 

  52. Jensen MD, Nathan T, Rafaelsen SR, Kjeldsen J. Diagnostic accuracy of capsule endoscopy for small bowel Crohn’s disease is superior to that of MR enterography or CT enterography. Clin Gastroenterol Hepatol. 2011;9:124–9.

    Article  PubMed  Google Scholar 

  53. Efthymiou A, Viazis N, Mantzaris G, Papadimitriou N, Tzourmakliotis D, Raptis S, et al. Does clinical response correlate with mucosal healing in patients with Crohn’s disease of the small bowel? A prospective, case-series study using wireless capsule endoscopy. Inflamm Bowel Dis. 2008;14:1542–7.

    Article  PubMed  Google Scholar 

  54. Cheifetz AS, Kornbluth AA, Legnani P, Schmelkin I, Brown A, Lichtiger S, et al. The risk of retention of the capsule endoscope in patients with known or suspected Crohn’s disease. Am J Gastroenterol. 2006;101:2218–22.

    Article  PubMed  Google Scholar 

  55. Sung J, Ho KY, Chiu HM, Ching J, Travis S, Peled R. The use of Pillcam Colon in assessing mucosal inflammation in ulcerative colitis: a multicenter study. Endoscopy. 2012;44:754–8.

    Article  PubMed  CAS  Google Scholar 

  56. Kato J, Kuriyama M, Hiraoka S, Yamamoto K. Is sigmoidoscopy sufficient for evaluating inflammatory status of ulcerative colitis patients? J Gastroenterol Hepatol. 2011;26:683–7.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Second Department of Internal Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama, 641-0012, Japan

    Jun Kato & Masao Ichinose

  2. Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

    Sakiko Hiraoka & Asuka Nakarai

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  1. Jun Kato
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  2. Sakiko Hiraoka
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  4. Masao Ichinose
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Correspondence to Jun Kato.

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Kato, J., Hiraoka, S., Nakarai, A. et al. Noninvasive evaluation of mucosal healing in inflammatory bowel diseases. Clin J Gastroenterol 6, 1–7 (2013). https://doi.org/10.1007/s12328-012-0346-x

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