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Ulcerative colitis  
It is not possible to examine the whole surface of the colon in the endomicroscopic mode. In patients with ulcerative colitis, it is therefore important to combine endomicroscopy with chromoendoscopy. Panchromoendoscopy with either methylene blue or indigo carmine is a valid diagnostic tool for improving the diagnostic yield of intraepithelial neoplasia using the “SURFACE” recommendations. Chromoendoscopy can reveal circumscribed lesions, and chromoscopy-guided confocal laser endomicroscopy can be used to predict intraepithelial neoplasias with a high degree of accuracy. Targeted biopsies of relevant lesions can therefore be taken, and rapid confirmation of neoplastic changes using confocal laser endoscopy during colonoscopy may lead to significant improvements in the clinical management of patients with ulcerative colitis. In 41 patients with long-term ulcerative colitis who were in clinical remission, endomicroscopy in conjunction with methylene blue-aided panchromoendoscopy was used for surveillance. Chromoendoscopy with methylene blue did not lead to any interference with the laser scanning system.

A total of 14596 confocal images from 464 different locations (369 inconspicuous areas, 95 circumscribed lesions) were compared with the histological results from 1392 biopsies. Sixtyseven of 95 circumscribed lesions were only visible after chromoendoscopy with methylene blue. Different cellular structures (epithelial and blood cells), capillaries, and connective tissue limited to the mucosal layer were identified by confocal microscopy. Due to the pharmacokinetic properties of fluorescein, nuclei could not be seen. However, the presence of neoplastic changes (sensitivity 94.4 %, specificity 95.6 %, accuracy 99.3 %) and inflammation were predictable with a high degree of accuracy.

In the first randomized trial of endomicroscopy (Kiesslich et al., Gastroenterology 2007), 153 patients with long-term ulcerative colitis who were in clinical remission were randomly assigned at a ratio of 1 : 1 to undergo either conventional colonoscopy or panchromoendoscopy using 0.1% methylene blue in conjunction with endomicroscopy to detect intraepithelial neoplasia or colorectal cancer. Circumscribed lesions in the colonic mucosa detected by chromoendoscopy were evaluated with endomicroscopy for cellular and vascular changes in accordance with the confocal pattern classification for predicting neoplasia. Targeted biopsies from the areas examined were taken and histologically graded according to the World Health Organization and new Vienna classification.

In the standard colonoscopy group, randomized biopsies every 10 cm between the anus and cecum were taken, as well as targeted biopsies of visible mucosal changes. The primary outcome analysis was a histological diagnosis of neoplasia. Using chromoendoscopy in conjunction with endomicroscopy (80 patients, average examination time 42 min), significantly more intraepithelial neoplasia was detected (19 versus 4 cases; P=0.007) than with standard colonoscopy (73 patients, average examination time 31 min). Endomicroscopy revealed different cellular structures (epithelial and blood cells), capillaries, and connective tissue limited to the mucosal layer. A total of 5580 confocal images from 134 circumscribed lesions were compared with the histological results from 311 biopsies. The presence of neoplastic changes was predicted with a high degree of accuracy (sensitivity 94.7 %, specificity 98.3 %, accuracy 97.8%).
       

       
In summary, chromoendoscopy is able to reveal circumscribed lesions, and confocal laser microscopy can be used to confirm intraepithelial neoplasias with a high degree of accuracy. Biopsies can therefore be limited to targeted sampling of relevant lesions. In vivo histology with endomicroscopy may lead to significant improvements in the clinical management of patients with ulcerative colitis, with reduced numbers of biopsies being needed for confirmation of the condition and time being gained for immediate therapeutic intervention.
   
Collagenous colitis  
Endomicroscopy makes it possible to locate and measure the distribution and thickness of collagenous bands underneath the epithelial layer, thus allowing targeted biopsies - a new approach in collagenous colitis, particularly in cases with disrupted subepithelial collagen deposits. At present, randomized biopsies are recommended, preferably from the right colon. The distribution of the collagenous bands can be patchy and segmental in the colon. Confocal endomicroscopy helps differentiate between affected and normal sites and can guide biopsies.