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DOI: 10.1055/s-0034-1393314
Confocal laser endomicroscopy: a novel method for prediction of relapse in Crohn’s disease
Publikationsverlauf
submitted: 14. April 2015
accepted after revision: 25. August 2015
Publikationsdatum:
19. November 2015 (online)
![](https://www.thieme-connect.de/media/endoscopy/201604/lookinside/thumbnails/12409_10-1055-s-0034-1393314-1.jpg)
Background and study aims: Confocal laser endomicroscopy (CLE) has been shown to predict relapse in ulcerative colitis in remission, but little is currently known about its role in Crohn’s disease. The aim of this study was to identify reproducible CLE features in patients with Crohn’s disease and to examine whether these are risk factors for relapse.
Patients and methods: This was a single-center prospective feasibility study of CLE imaging in patients with Crohn’s disease. CLE imaging was performed in the terminal ileum and four colorectal sites, and was correlated with histopathology and macroscopic appearance. Clinical relapse, defined as the need for treatment escalation or surgical intervention, was recorded during follow-up.
Results: The study included 50 patients: 39 with Crohn’s disease (20 in remission), and 11 controls. Ileal fluorescein leakage and microerosions were significantly more frequent in patients with endoscopically active Crohn’s disease compared with patients with inactive Crohn’s disease and controls (P = 0.005 and (P = 0.006, respectively). The same applied to colorectal fluorescein leakage and vascular alterations ((P = 0.043 and (P = 0.034, respectively). During a 12-month follow-up period, ileal fluorescein leakage and microerosions were significant risk factors for relapse in the subgroup of patients in remission (log rank (P = 0.009 and (P = 0.007, respectively) as well as in the entire group of patients with Crohn’s disease (log rank (P = 0.006 and (P = 0.01, respectively). Inter- and intraobserver reproducibility was almost perfect (κ > 0.80) or substantial (κ > 0.60) for the majority of CLE parameters.
Conclusions: CLE can identify reproducible microscopic changes in the terminal ileum that are risk factors for relapse in patients with otherwise inactive Crohn’s disease.
Trial registration: ClinicalTrials.gov (NCT01738529).
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References
- 1 Thia KT, Sandborn WJ, Harmsen WS et al. Risk factors associated with progression to intestinal complications of Crohn’s disease in a population-based cohort. Gastroenterology 2010; 139: 1147-1155
- 2 Annese V, Daperno M, Rutter MD et al. European evidence based consensus for endoscopy in inflammatory bowel disease. J Crohns Colitis 2013; 7: 982-1018
- 3 Walsh A, Palmer R, Travis S. Mucosal healing as a target of therapy for colonic inflammatory bowel disease and methods to score disease activity. Gastrointest Endosc Clin N Am 2014; 24: 367-378
- 4 D’Haens G, Baert F, van Assche G et al. Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn’s disease: an open randomised trial. Lancet 2008; 371: 660-667
- 5 Rutgeerts P, Diamond RH, Bala M et al. Scheduled maintenance treatment with infliximab is superior to episodic treatment for the healing of mucosal ulceration associated with Crohn’s disease. Gastrointest Endosc 2006; 63: 433-442
- 6 Baert F, Moortgat L, Van Assche G et al. Mucosal healing predicts sustained clinical remission in patients with early-stage Crohn’s disease. Gastroenterology 2010; 138: 463-468
- 7 Ferrante M, Colombel JF, Sandborn WJ et al. Validation of endoscopic activity scores in patients with Crohn’s disease based on a post hoc analysis of data from SONIC. Gastroenterology 2013; 145: 978-986
- 8 Solberg IC, Vatn MH, Hoie O et al. Clinical course in Crohn’s disease: results of a Norwegian population-based ten-year follow-up study. Clin Gastroenterol Hepatol 2007; 5: 1430-1438
- 9 Louis E, Mary JY, Vernier-Massouille G et al. Maintenance of remission among patients with Crohn’s disease on antimetabolite therapy after infliximab therapy is stopped. Gastroenterology 2012; 142: 63-70
- 10 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 Therapeutiques des Affections Inflammatoires du Tube Digestif (GETAID). Gut 1989; 30: 983-989
- 11 Daperno M, D’Haens G, Van Assche G et al. Development and validation of a new, simplified endoscopic activity score for Crohn’s disease: the SES-CD. Gastrointest Endosc 2004; 60: 505-512
- 12 Korelitz BI, Sommers SC. Response to drug therapy in Crohn’s disease: evaluation by rectal biopsy and mucosal cell counts. J Clin Gastroenterol 1984; 6: 123-127
- 13 Neumann H, Kiesslich R, Wallace MB et al. Confocal laser endomicroscopy: technical advances and clinical applications. Gastroenterology 2010; 139: 388-392
- 14 Wanders LK, East JE, Uitentuis SE et al. Diagnostic performance of narrowed spectrum endoscopy, autofluorescence imaging, and confocal laser endomicroscopy for optical diagnosis of colonic polyps: a meta-analysis. Lancet Oncol 2013; 14: 1337-1347
- 15 Peeters M, Ghoos Y, Maes B et al. Increased permeability of macroscopically normal small bowel in Crohn’s disease. Dig Dis Sci 1994; 39: 2170-2176
- 16 Wyatt J, Vogelsang H, Hubl W et al. Intestinal permeability and the prediction of relapse in Crohn’s disease. Lancet 1993; 341: 1437-1439
- 17 Buda A, Hatem G, Neumann H et al. Confocal laser endomicroscopy for prediction of disease relapse in ulcerative colitis: a pilot study. J Crohns Colitis 2014; 8: 304-311
- 18 Kiesslich R, Duckworth CA, Moussata D et al. Local barrier dysfunction identified by confocal laser endomicroscopy predicts relapse in inflammatory bowel disease. Gut 2012; 61: 1146-1153
- 19 Li CQ, Liu J, Ji R et al. Use of confocal laser endomicroscopy to predict relapse of ulcerative colitis. BMC Gastroenterol 2014; 14: 45
- 20 Sipponen T, Nuutinen H, Turunen U et al. Endoscopic evaluation of Crohn’s disease activity: comparison of the CDEIS and the SES-CD. Inflamm Bowel Dis 2010; 16: 2131-2136
- 21 D’Haens GR, Geboes K, Peeters M et al. Early lesions of recurrent Crohn’s disease caused by infusion of intestinal contents in excluded ileum. Gastroenterology 1998; 114: 262-267
- 22 Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics 1977; 33: 159-174
- 23 Bonett DG. Sample size requirements for estimating intraclass correlations with desired precision. Stat Med 2002; 21: 1331-1335
- 24 Van Assche G, Dignass A, Panes J et al. The second European evidence-based consensus on the diagnosis and management of Crohn’s disease: definitions and diagnosis. J Crohns Colitis 2010; 4: 7-27
- 25 Kiesslich R, Goetz M, Angus EM et al. Identification of epithelial gaps in human small and large intestine by confocal endomicroscopy. Gastroenterology 2007; 133: 1769-1778
- 26 Liu JJ, Wong K, Thiesen AL et al. Increased epithelial gaps in the small intestines of patients with inflammatory bowel disease: density matters. Gastrointest Endosc 2011; 73: 1174-1180
- 27 Moussata D, Goetz M, Gloeckner A et al. Confocal laser endomicroscopy is a new imaging modality for recognition of intramucosal bacteria in inflammatory bowel disease in vivo. Gut 2011; 60: 26-33
- 28 Lim LG, Neumann J, Hansen T et al. Confocal endomicroscopy identifies loss of local barrier function in the duodenum of patients with Crohn’s disease and ulcerative colitis. Inflamm Bowel Dis 2014; 20: 892-900
- 29 Neumann H, Vieth M, Atreya R et al. Assessment of Crohn’s disease activity by confocal laser endomicroscopy. Inflamm Bowel Dis 2012; 18: 2261-2269
- 30 Becker V, von Delius S, Bajbouj M et al. Intravenous application of fluorescein for confocal laser scanning microscopy: evaluation of contrast dynamics and image quality with increasing injection-to-imaging time. Gastrointest Endosc 2008; 68: 319-323
- 31 Li CQ, Xie XJ, Yu T et al. Classification of inflammation activity in ulcerative colitis by confocal laser endomicroscopy. Am J Gastroenterol 2010; 105: 1391-1396