Prediction of clinical outcomes in Crohn's disease by using confocal laser endomicroscopy: results from a prospective multicenter study.

BACKGROUND AND AIMS: Assessment of prognostic factors in patients with Crohn's disease (CD) is of pivotal importance for early intervention and "treat-to-target" strategies. Confocal laser endomicroscopy (CLE) enables on-demand in vivo characterization of mucosal inflammatory and architectural changes during endoscopy. We prospectively assessed the value of CLE for prediction of clinical outcome parameters in CD. METHODS: Consecutive patients with CD undergoing colonoscopy were included in a multicenter study. Confocal imaging focused on 2 highly reproducible histologic hallmarks of active colonic inflammation: focal cryptitis and crypt architectural abnormality. We evaluated whether CLE, CD endoscopic index of severity (CDEIS), serum C-reactive protein (CRP), and CD activity index (CDAI) were associated with the risk of medical treatment escalation, transmural adverse events, and CD-related hospitalization or surgery during a 4-year follow-up. RESULTS: Among 49 patients (53% men, median age, 39 years), baseline CRP was ≥5 mg/L in 47%, CDEIS ≥3 in 75%, and CDAI >150 in 51%. Focal cryptitis and crypt architectural abnormality were observed in 63% (CLE+ group). CLE+ patients showed an increased incidence of medical treatment escalation (P < .001; relative risk [RR] = 3.27) and transmural lesions (P = .025; RR = 1.70), whereas patients with CRP ≥5 mg/L had increased CD-related hospitalization and surgery (P = .020, RR = 2.71) at 1-year follow-up. No further association with prognostic clinical outcomes was found over the 1-year follow-up as well as for CDEIS and CDAI at any time. CONCLUSIONS: CLE reveals CD-related features of mucosal inflammation and allows for early prediction of relevant clinical outcomes. Further studies should now address whether this promising prognostic tool could refine the timing of treatment strategies in patients with CD.

Evolving endoscopic technologies for the detection of dysplasia in inflammatory bowel diseases.

Patients with long-standing and extensive ulcerative colitis (UC) and colonic Chron's disease (CD) have an increased risk of CRC compared with the general population. Although no large controlled trials have proven that surveillance reduces mortality, cancer prevention in inflammatory bowel disease depends on the detection of dysplasia during scheduled surveillance colonoscopy and is widely recommended by gastroenterological associations. Dysplasia in IBD may occur in flat mucosa or in raised lesions (DALM) which have sometimes endoscopic features similar to adenoma (adenoma-like DALM). Recently, new endoscopic techniques to facilitate the distinction between dysplastic and actively inflamed or normal mucosa have been proposed. Chromoendoscopy significantly increases the sensitivity of detecting subtle dysplastic lesions and has emerged as the new standard of cancer surveillance in patients with IBD. Confocal laser endomicroscopy (CLE) is a novel technique that enables the endoscopist to obtain real time in vivo microscopic images of the gastrointestinal mucosa and can be used for targeting biopsies to relevant areas. CLE in conjunction with chromoendoscopy proved able to increase the diagnostic yield of dysplasia in ulcerative colitis and reduce the number of biopsies needed. The role of digital filtering technologies (virtual chromoendoscopy) and autofluorescence in IBD surveillance will be also discussed.

Detection of a fluorescent-labeled avidin-nucleic acid nanoassembly by confocal laser endomicroscopy in the microvasculature of chronically inflamed intestinal mucosa.

Inflammatory bowel diseases are chronic gastrointestinal pathologies causing great discomfort in both children and adults. The pathogenesis of inflammatory bowel diseases is not yet fully understood and their diagnosis and treatment are often challenging. Nanoparticle-based strategies have been tested in local drug delivery to the inflamed colon. Here, we have investigated the use of the novel avidin-nucleic acid nanoassembly (ANANAS) platform as a potential diagnostic carrier in an experimental model of inflammatory bowel diseases. Fluorescent- labeled ANANAS nanoparticles were administered to mice with chemically induced chronic inflammation of the large intestine. Localization of mucosal nanoparticles was assessed in vivo by dual-band confocal laser endomicroscopy. This technique enables characterization of the mucosal microvasculature and crypt architecture at subcellular resolution. Intravascular nanoparticle distribution was observed in the inflamed mucosa but not in healthy controls, demonstrating the utility of the combination of ANANAS and confocal laser endomicroscopy for highlighting intestinal inflammatory conditions. The specific localization of ANANAS in inflamed tissues supports the potential of this platform as a targeted carrier for bioactive moieties in the treatment of inflammatory bowel disease.

Confocal laser endomicroscopy for prediction of disease relapse in ulcerative colitis: a pilot study.

BACKGROUND AND AIMS: Neoangiogenesis and increased endothelial permeability are observed as results of chronic intestinal inflammation. However, limited data on microvascular and crypt architecture during remission phases is available. The aim of this prospective investigator blinded cohort study was to assess crypt and microvascular architecture and function in ulcerative colitis by probe based confocal laser endomicroscopy; we also evaluated whether these findings may have the potential to predict disease relapse. METHODS: 19 ulcerative colitis patients in clinical and endoscopic remission and 19 controls were studied. A computer based image processing technique was applied to construct 20 mosaicing image sets from each subject. Remitting patients were sub-grouped into either inactive or quiescent disease according to histology. RESULTS: Pericrypt fluorescence (p<0.01), crypt diameter (p<0.05) but not intercrypt distance (p=0.07) were significantly increased in ulcerative colitis patients compared to controls. Patients with inactive disease showed a significant increase in fluorescence leakage (median fluorescence (IQR), 3888 (3560-4240) vs. 2696 (2502-3390), p<0.01), crypt diameter (median diameter (IQR), 92.5 (85.5-101) vs. 73 (70-77), p<0.05) and intercrypt distance (median distance (IQR), 82.5 (70.5-91.2) vs. 66 (59.5-73.5), p<0.05) compared to those with quiescent disease. A composite outcome score combining fluorescence leakage and crypt diameter was able to predict a disease flare during a 12 month follow-up period (p<0.01). CONCLUSIONS: In vivo intramucosal changes detected by confocal endomicroscopy in ulcerative colitis remittent patients can predict disease relapse. This observation may have further implications for disease management and medical treatment.

Granulo-monocyto apheresis is more effective in mild ulcerative colitis than in moderate to severe disease.

AIM: To evaluate whether the effectiveness of Granulo-monocyto apheresis (GMA), a technique that consists of the extracorporeal removal of granulocytes and monocytes from the peripheral blood, might vary according to the severity of ulcerative colitis (UC) in patients with mild to moderate-severe disease UC activity. METHODS: We retrospectively reviewed prospectively collected data of patients undergoing GMA at our inflammatory bowel disease centre who had at least a 6 mo of follow-up. The demographics, clinical and laboratory data were extracted from the patients' charts and electronic records. The severity of UC was scored according to the Modified Truelove Witts Severity Index (MTWSI). A clinical response was defined as a decrease from baseline of ≥ 2 points or a value of MTWSI ≤ 2 points. RESULTS: A total of 41 (24 males/17 females; mean age 47 years) patients were included in the study. After GMA cycle completion, 21/28 (75%) of mild UC patients showed a clinical response compared with 7/13 (54%) of patients with moderate to severe disease (P = 0.27). At 6-mo, 14/28 (50%) of the mild UC patients maintained a clinical response compared with 2/13 (15%) of the patients with moderate to severe disease (P = 0.04). After the GMA cycle completion and during the 6-mo follow up period, 13/16 (81%) and 9/16 (56%) of mild UC patients with intolerance, resistance and contraindications to immunosuppressants and/or biologics showed a clinical response compared with 2/6 (33%) and 0/6 (0%) of patients with moderate to severe disease activity with these characteristics (P = 0.05 and P = 0.04, respectively). CONCLUSION: Patients with mild UC benefit from GMA more than patients with moderate to severe disease in the short-term period. GMA should be considered a valid therapeutic option in cases of contraindications to immunosuppressants, corticosteroids and/or biologics.