Reply to Gheorghe et al.

We read with great interest the comment from Gheorghe et al. regarding our manuscript entitled “Endocytoscopy can be used to assess histological healing in ulcerative colitis” [1]. In the paper, we confirmed that endocytoscopy (ECS) can be used to assess the histological healing of the rectum in patients with ulcerative colitis (UC) without the need for biopsy specimens. As pointed out by Gheorghe et al., our study did not conduct any endoscopic or histological assessment using ECS at any site other than the rectum. In our preliminary experiences with ECS, crypt elongation and intercryptal infiltration of inflammatory cells were more frequently observed in the rectum and sigmoid colon than in other sites of the colon in most patients who had complete endoscopic remission. Therefore, we assessed the ECS scores (ECSS) for the rectum in our recent studies. Narrow-band imaging (NBI) of ECS is useful for assessing shape of crypt, crypt density, and vascular alterations, and it can be used to assess the histological healing of the entire colon without the need for chromoendoscopy.

We understand that there are discrepancies among the clinical, endoscopic, and histological severity findings, as Gheorghe et al. pointed out. However, the improvements in the clinical symptoms of UC are most important for patients with UC in a clinical setting. Our study indicated that only 7.4 % of patients with an ECSS of 0 had clinical recurrence during the follow-up period. This information may be useful for patients with UC [1]. Karstensen et al. also defined relapse as the need for treatment escalation or surgical intervention, which was considered clinical relapse in their paper, which confirmed the usefulness of confocal laser endomicroscopy (CLE) for the prediction of relapse in Crohn’s disease [2]. CLE enables real-time in vivo microscopy and the assessment of crypt distortion, crypt density, vascular alteration, inflammatory infiltrates, and fluorescein leakage in patients with UC and Crohn’s disease [2] [3] [4]. Recent studies have indicated that the endoscopic score from CLE correlated with the histological severity, and that CLE is useful for predicting relapse [2], response to medical treatment [5], or impaired intestinal permeability in patients with inflammatory bowel disease [6]. It should be noted that sodium fluorescein was injected intravenously during the CLE procedures. The injection of sodium fluorescein is considered safe, but minor complications have been reported in 1.4 % of individuals [7]. Additionally, the long-term safety in patients who received sodium fluorescein should be evaluated in a prospective study.

At present, both diagnostic techniques (ECS and CLE) can only be used in a limited number of institutions. We believe that it is important that ECS and CLE be more widely available to assess whether these diagnostic methods are useful in a real clinical setting.

• References

• 1 Nakazato Y, Naganuma M, Sugimoto S. et al. Endocytoscopy can be used to assess histological healing in ulcerative colitis. Endoscopy 2017; 49: 560-563
• 2 Karstensen JG, Săftoiu A, Brynskov J. et al. Confocal laser endomicroscopy: a novel method for prediction of relapse in Crohn’s disease. Endoscopy 2016; 48: 364-372
• 3 Neumann H, Kiesslich R, Wallace MB. et al. Confocal laser endomicroscopy: technical advances and clinical applications. Gastroenterology 2010; 139: 388-392
• 4 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
• 5 Karstensen JG, Săftoiu A, Brynskov J. et al. Confocal laser endomicroscopy in ulcerative colitis: a longitudinal study of endomicroscopic changes and response to medical therapy (with videos). Gastrointest Endosc 2016; 84: 279-286
• 6 Chang J, Leong RW, Wasinger V. et al. Impaired intestinal permeability contributes to ongoing bowel symptoms in patients with inflammatory bowel disease and mucosal healing. Gastroenterology 2017; 153: 723-731 .e1
• 7 Wallace MB, Meining A, Canto MI. et al. The safety of intravenous fluorescein for confocal laser endomicroscopy in the gastrointestinal tract. Aliment Pharmacol Ther 2010; 31: 548-552