Breaks in the wall: increased gaps in the intestinal epithelium of irritable bowel syndrome patients identified by confocal laser endomicroscopy (with videos)

Turcotte, J.; Kao, Dina; Mah, Stephanie J.; Claggett, Brian; Saltzman, John R.; Fedorak, Richard N.; Liu, Julia J.

doi:10.1016/j.gie.2012.11.006

Cited by 48 publications

(48 citation statements)

References 26 publications

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“…The epithelial gaps or extrusion zones may be the potential entry sites for luminal microbes into the host (10). The epithelial gap density—a validated measure of epithelial cell extrusion (12)—is increased in most patients with IBD compared with healthy controls: 93% of the patients with Crohn disease and 75% of the patients with ulcerative colitis have elevated gap density (13). In adult patients with IBD, normal epithelial barrier function as determined by CLE examination was associated with only a 20% risk of disease relapse and a 5% risk of major events (hospitalization/surgery) occurring within 1 year (14,15).…”

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confidence: 99%

A Pilot Study of Confocal Laser Endomicroscopy to Predict Barrier Dysfunction and Relapse in Pediatric Inflammatory Bowel Disease

Шавров

Kharitonova

Davis

et al. 2016

J. pediatr. gastroenterol. nutr.

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Objectives Probe-based confocal laser endomicroscopy (pCLE) is a novel imaging modality that enables virtual optical biopsy in vivo. Loss of barrier function of the small bowel observed via pCLE as increased density of epithelial gaps (extrusion zones left in the intestinal lining after cells are shed) is predictive of relapse in adult patients with inflammatory bowel disease (IBD). This study aims to determine whether such observations on pCLE are similarly predictive of disease relapse in pediatric patients with IBD. Methods Pediatric patients with biopsy-proven IBD underwent pCLE during colonoscopy and subsequent clinical follow-up every 6 months. Relapse was defined as moderate to severe flare with endoscopic evidence of inflammation during the follow-up period. The relations between epithelial gap density, disease relapse, and imaging parameters were determined using Cox models. Results Twenty-four patients with IBD (13 with Crohn disease, 11 with ulcerative colitis) with a median age of 14 years (range 10–21) were studied for a median of 13 (4–33) months. The median duration of disease was 2.9 years (range 0–9). Increased epithelial gap density in the terminal ileum on pCLE of normal endoscopic appearing terminal ileum mucosa (N = 19) was predictive of disease relapse when 3 or more areas were imaged (N = 6, log-rank P = 0.02, C-statistic = 0.94). Conclusions In pediatric patients with IBD, barrier dysfunction observed on pCLE imaging of the small bowel was predictive of disease relapse.

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confidence: 99%

A Pilot Study of Confocal Laser Endomicroscopy to Predict Barrier Dysfunction and Relapse in Pediatric Inflammatory Bowel Disease

Шавров

Kharitonova

Davis

et al. 2016

J. pediatr. gastroenterol. nutr.

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“…Similarly, pCLE was used to identify an increased gap density in the terminal ileum of patients with IBS versus healthy individuals as controls. 58 This finding might indicate increased cell extrusion as a micro architectural correlate of altered mucosal permeability observed in these patients. It also exemplifies the way that CLE might contribute to our u nderstanding of disease p athogenesis by in vivo imaging.…”

Section: Translational Science: Functional Imagingmentioning

confidence: 87%

Microscopic imaging in endoscopy: endomicroscopy and endocytoscopy

Goetz

Malek

Kießlich

2013

Nat Rev Gastroenterol Hepatol

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Performing real-time microscopy has been a vision of endoscopists since the very early phases of gastrointestinal endoscopy. Confocal endomicroscopy, an adaption of confocal laser scanning microscopy, and endocytoscopy, an adaption of white-light microscopy, have been introduced into the endoscopic armamentarium in the past decade. Both techniques yield on-site histological information. Multiple trials have demonstrated the ability of gastroenterologists to obtain and interpret microscopic images from the upper and lower gastrointestinal tract, and also the hepatobiliary-pancreatic system, during endoscopy. Such microscopic information has been successfully used in expert hands to minimize sampling error by 'smart', microscopically targeted biopsies and to guide endoscopic interventions. However, endomicroscopy is also unique in its ability to dynamically visualize cellular processes in their native environment free of artefacts. This ability enables fundamental insights into mechanisms of human diseases in clinical and translational science.

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“…Fluorescence endomicroscopy also enables observation of gaps or breaks in the intestinal epithelial lining [59][60][61] . For patients with IBS 60,61 the leakage of intravenous fluorescein into the lumen has been visualized in real time 61 , indicating that endomicroscopy can be used to monitor dynamic, cellular level changes in gut function and permeability.…”

Section: Microbiota Changesmentioning

confidence: 99%

The potential role of optical biopsy in the study and diagnosis of environmental enteric dysfunction

Thompson

Hughes

Anastasova

et al. 2017

Nat Rev Gastroenterol Hepatol

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| Environmental enteric dysfunction (EED) is a disease of the small intestine affecting children and adults in low and middle income countries. Arising as a consequence of repeated infections, gut inflammation results in impaired intestinal absorptive and barrier function, leading to poor nutrient uptake and ultimately to stunting and other developmental limitations. Progress towards new biomarkers and interventions for EED is hampered by the practical and ethical difficulties of cross-validation with the gold standard of biopsy and histology. Optical biopsy techniques -which can provide minimally invasive or noninvasive alternatives to biopsy -could offer other routes to validation and could potentially be used as point-of-care tests among the general population. This Consensus Statement identifies and reviews the most promising candidate optical biopsy technologies for applications in EED, critically assesses them against criteria identified for successful deployment in developing world settings, and proposes further lines of enquiry. Importantly, many of the techniques discussed could also be adapted to monitor the impaired intestinal barrier in other settings such as IBD, autoimmune enteropathies, coeliac disease, graft-versus-host disease, small intestinal transplantation or critical care. Members of the board and experts met to discuss the horizon scan in London, UK, in November 2015 and San Francisco, USA, in February 2016. Literature searches were performed using Web of Science, as well as through the advice of the advisory board and experts. The results of the horizon scan are presented in this Consensus Statement, which entails a review of EED, a discussion of technologies deemed relevant to EED (based on literature searches and the opinions of the advisory board and experts), and a series of recommendations for the future application of the rele vant technologies to the study and diagnosis of EED. In the Recommendations section, each technology has been assessed according to its suitability for application to EED and this assessment includes an evaluation of the cost, invasiveness and appropriateness for developing countries of each device and/or technique. This assessment was performed in a qualitative manner based on currently available information (for example, the present cost and size of the devices) and the opinions of the authors as to feasible future develop ment. Technique suitability for use in developing countries was determined in a qualitative manner after consideration of the need for advanced infrastructure and high levels of training for either system use or data analysis. Probable deployment time scales have also been assigned to each technique based on the current states of development and the degree of valid ation work that will be required before application to EED. These timescales have been tentatively defined as short-term (suitable for deployment immediately or within ~1 year), mediumterm (suit able for deployment within ~1-3 years) and long-term (suitable for deployme...

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Breaks in the wall: increased gaps in the intestinal epithelium of irritable bowel syndrome patients identified by confocal laser endomicroscopy (with videos)

Cited by 48 publications

References 26 publications

A Pilot Study of Confocal Laser Endomicroscopy to Predict Barrier Dysfunction and Relapse in Pediatric Inflammatory Bowel Disease

A Pilot Study of Confocal Laser Endomicroscopy to Predict Barrier Dysfunction and Relapse in Pediatric Inflammatory Bowel Disease

Microscopic imaging in endoscopy: endomicroscopy and endocytoscopy

The potential role of optical biopsy in the study and diagnosis of environmental enteric dysfunction

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