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Background & Aims: Microscopic inflammation has significant prognostic value in ulcerative colitis (UC); however, its assessment is complex with high interobserver variability. We aimed to develop and validate an artificial intelligence (AI) computer-aided diagnosis system to evaluate UC biopsies and predict prognosis., Methods: A total of 535 digitalized biopsies (273 patients) were graded according to the PICaSSO Histologic Remission Index (PHRI), Robarts, and Nancy Histological Index. A convolutional neural network classifier was trained to distinguish remission from activity on a subset of 118 biopsies, calibrated on 42 and tested on 375. The model was additionally tested to predict the corresponding endoscopic assessment and occurrence of flares at 12 months. The system output was compared with human assessment. Diagnostic performance was reported as sensitivity, specificity, prognostic prediction through Kaplan-Meier, and hazard ratios of flares between active and remission groups. We externally validated the model in 154 biopsies (58 patients) with similar characteristics but more histologically active patients., Results: The system distinguished histological activity/remission with sensitivity and specificity of 89% and 85% (PHRI), 94% and 76% (Robarts Histological Index), and 89% and 79% (Nancy Histological Index). The model predicted the corresponding endoscopic remission/activity with 79% and 82% accuracy for UC endoscopic index of severity and Paddington International virtual ChromoendoScopy ScOre, respectively. The hazard ratio for disease flare-up between histological activity/remission groups according to pathologist-assessed PHRI was 3.56, and 4.64 for AI-assessed PHRI. Both histology and outcome prediction were confirmed in the external validation cohort., Conclusion: We developed and validated an AI model that distinguishes histologic remission/activity in biopsies of UC and predicts flare-ups. This can expedite, standardize, and enhance histologic assessment in practice and trials., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Histological remission is evolving as an important treatment target in UC. We aimed to develop a simple histological index, aligned to endoscopy, correlated with clinical outcomes, and suited to apply to an artificial intelligence (AI) system to evaluate inflammatory activity., Methods: Using a set of 614 biopsies from 307 patients with UC enrolled into a prospective multicentre study, we developed the Paddington International virtual ChromoendoScopy ScOre (PICaSSO) Histologic Remission Index (PHRI). Agreement with multiple other histological indices and validation for inter-reader reproducibility were assessed. Finally, to implement PHRI into a computer-aided diagnosis system, we trained and tested a novel deep learning strategy based on a CNN architecture to detect neutrophils, calculate PHRI and identify active from quiescent UC using a subset of 138 biopsies., Results: PHRI is strongly correlated with endoscopic scores (Mayo Endoscopic Score and UC Endoscopic Index of Severity and PICaSSO) and with clinical outcomes (hospitalisation, colectomy and initiation or changes in medical therapy due to UC flare-up). A PHRI score of 1 could accurately stratify patients' risk of adverse outcomes (hospitalisation, colectomy and treatment optimisation due to flare-up) within 12 months. Our inter-reader agreement was high (intraclass correlation 0.84). Our preliminary AI algorithm differentiated active from quiescent UC with 78% sensitivity, 91.7% specificity and 86% accuracy., Conclusions: PHRI is a simple histological index in UC, and it exhibits the highest correlation with endoscopic activity and clinical outcomes. A PHRI-based AI system was accurate in predicting histological remission., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aims: A composite endoscopic-histologic remission is increasingly explored as an important endpoint in ulcerative colitis (UC). We investigated combined endoscopic-histologic remission for predicting clinical outcomes at 12 months compared with endoscopic remission alone using the high definition virtual chromoendoscopy (VCE) Paddington International virtual ChromoendoScopy ScOre (PICaSSO) and histology scores., Methods: Ulcerative colitis patients, prospectively enrolled from 11 international centres, underwent VCE with targeted biopsies and followed up for 12 months. Endoscopic activity was assessed by Mayo Endoscopic Score (MES), Ulcerative Colitis Endoscopic Index Severity (UCEIS) followed by VCE-PICaSSO. Robarts Histopathological Index|Robarts Histological index≤3 without neutrophils in mucosa, and Nancy Histological index (NHI)≤ 1 were used to define histologic remission. Combined endoscopic-histologic remission was compared with endoscopic remission alone by Cox proportional hazards model and by two- and three-proportion analysis using pre-specified clinical outcomes., Results: 307 patients were recruited and 302 analysed. There was no difference in survival without specified clinical outcomes between PICaSSO defined endoscopic remission alone and endoscopic plus histologic remission in the rectum (HR 0.42, 95%CI 0.16-1.11 and HR 1.03, 95%CI 0.42-2.52 for Robarts Histological index and NHI respectively) at 12 months. There was however a significant survival advantage without specified clinical outcome events for UCEIS combined with histology compared with UCEIS alone (HR 0.30, 95%CI 0.12-0.75, p = 0.02) at 12 months (but not combined with NHI). For MES there was no advantage for predicting specified clinical outcomes at 12 months for endoscopy alone versus endoscopy plus histology, but there were differences in two and three proportion analysis at 6 months., Conclusion: Endoscopic remission by VCE-PICaSSO alone was similar to combined endoscopic and histologic remission for predicting specified clinical outcomes at 12 months. Larger studies with specific therapeutic interventions are required to further confirm the findings., (© 2021 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Introduction: Surveillance colonoscopy is recommended in patients with long standing ulcerative colitis or Crohn's colitis. Chromoendoscopy is the main technique for increased detection of colitis-associated dysplasia. However, the recommendation was made on the basis of studies using standard definition colonoscopes., Purpose of Review: This review highlights randomized controlled trials and meta-analysis, which were published between 2018 and 2021 with the focus of conventional chromoendoscopy, virtual chromoendoscopy and high-definition imaging. In addition, studies investigating the value of random biopsies were also evaluated., Recent Findings: Chromoendoscopy increases the total number of colitis-associated dysplasia even by using high-definition colonoscopes. However, the procedure time is prolonged and there is no significant difference in the diagnostic yield of high definition alone and high definition with chromoendoscopy. Virtual chromoendoscopy seems not to develop a role for surveillance in inflammatory bowel disease (IBD) patients., Summary: High-definition colonoscopy and conventional chromoendoscopy are key techniques for surveillance in IBD., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background & Aims: Endoscopic and histologic remission are important goals in the treatment of ulcerative colitis (UC). We investigated the correlation of the recently developed Paddington International Virtual ChromoendoScopy ScOre (PICaSSO) and other established endoscopic scores against multiple histological indices and prospectively assessed outcomes., Methods: In this prospective multicenter international study, inflammatory activity was assessed with high-definition and virtual chromoendoscopy in the rectum and sigmoid using the Mayo Endoscopic Score (MES), UC Endoscopic Index of Severity (UCEIS), and PICaSSO. Targeted biopsies were taken for assessment using Robarts Histological Index (RHI), Nancy Histological index (NHI), ECAP (Extent, Chronicity, Activity, Plus score), Geboes, and Villanacci. Follow-up data were obtained at 6 and 12 months after colonoscopy., Results: A total of 307 patients were recruited. There was strong correlation between PICaSSO and histology scores, significantly superior to correlation coefficients of MES and UCEIS with histology scores. A PICaSSO score of ≤3 detected histologic remission by RHI (≤3 + absence of neutrophils) with area under the receiver operating characteristic curve (AUROC) 0.90 (95% confidence interval [CI] 0.86-0.94) and NHI (≤1) AUROC 0.82 (95% CI 0.77-0.87). The interobserver agreement for PICaSSO was 0.88 (95% CI 0.83-0.92). At 6- and 12-months follow-up, PICaSSO score ≤3 predicted better outcomes than PICaSSO >3 (hazard ratio [HR] 0.19 [0.11-0.33] and 0.22 [0.13-0.34], respectively),} as well as PICaSSO 4-8 (HR 0.25 [0.12-0.53] and 0.22 (0.12-0.39), respectively) and similar to histologic remission., Conclusion: In this first real-life multicenter study, the PICaSSO score correlated strongly with multiple histological indices. Furthermore, PICaSSO score predicted specified clinical outcomes at 6 and 12 months, similar to histology. Thus, PICaSSO can be a useful endoscopic tool in the therapeutic management of UC., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Several studies have reported that ulcerative colitis [UC] patients with endoscopic mucosal healing may still have histological inflammation. We investigated the relationship between mucosal healing defined by modified PICaSSO [Paddington International Virtual ChromoendoScopy ScOre], Mayo Endoscopic Score [MES] and probe-based confocal laser endomicroscopy [pCLE] with histological indices in UC., Methods: A prospective study enrolling 82 UC patients [male 66%] was conducted. High-definition colonoscopy was performed to evaluate the activity of the disease with MES assessed with High-Definition MES [HD-MES] and modified PICaSSO and targeted biopsies were taken; pCLE was then performed. Receiver operating characteristic [ROC] curves were plotted to determine the best thresholds for modified PICaSSO and pCLE scores that predicted histological healing according to the Robarts Histopathology Index [RHI] and ECAP 'Extension, Chronicity, Activity, Plus' histology score., Results: A modified PICaSSO of ≤ 4 predicted histological healing at RHI ≤ 3, with sensitivity, specificity, accuracy and area under the ROC curve [AUROC] of 89.8%, 95.7%, 91.5% and 95.9% respectively. The sensitivity, specificity, accuracy and AUROC of HD-MES to predict histological healing by RHI were 81.4%, 95.7%, 85.4% and 92.1%, respectively. A pCLE ≤ 10 predicted histological healing with sensitivity of 94.9%, specificity of 91.3%, accuracy of 93.9% and AUROC of 96.5%. An ECAP of ≤ 10 was predicted by modified PICaSSO ≤ 4 with accuracy of 91.5% and AUROC of 95.9%., Conclusion: Histological healing by RHI and ECAP is accurately predicted by HD-MES and modified virtual electronic chromoendoscopy PICaSSO, endoscopic score; and the use of pCLE did not improve the accuracy any further., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aims: Electronic virtual chromoendoscopy (EVC) can demonstrate ongoing disease activity in ulcerative colitis (UC), even when Mayo subscores suggest healing. However, applicability of EVC technology outside the expert setting has yet to be determined., Methods: Fifteen participants across 5 centers reviewed a computerized training module outlining high-definition and EVC (iScan) colonoscopy modes. Interobserver agreement was then tested (Mayo score, Ulcerative Colitis Endoscopic Index of Severity [UCEIS], and the Paddington International Virtual Chromoendoscopy Score [PICaSSO] for UC), using a colonoscopy video library (30 cases reviewed pretraining and 30 post-training). Knowledge sustainability was retested in a second round (42 cases; 9/15 participants), 6 months after training provision., Results: Pretraining intraclass correlation coefficients (ICC) were good for the Mayo endoscopic subscore (ICC, .775), UCEIS scoring erosions/ulcers (ICC, .770), and UCEIS overall (ICC, .786) and for mucosal (ICC, .754) and vascular components of PICaSSO (ICC, .622). For the vascular components of UCEIS, agreement was only moderate (ICC, .429) and did not enhance post-training (ICC, .417); conversely, use of PICaSSO improved post-training (mucosal ICC, .848; vascular, .746). Histologic correlation using the New York Mt. Sinai System was strong for both PICaSSO components (Spearman's ρ for mucosal: .925; vascular, .873; P < .001 for both). Moreover, accuracy in specifically discriminating quiescent from mild histologic strata was strongest for PICaSSO (area under the receiver operating characteristic curve [AUROC] for mucosal, .781; vascular, .715) compared with Mayo (AUROC, .708) and UCEIS (AUROC for UCEIS overall, .705; vascular, .562; bleeding, .645; erosions/ulcers, .696). Inter-rater reliability for PICaSSO was sustained by round 2 participants (round 1 and 2 ICC for mucosal, .873 and .869, respectively; vascular, .715 and .783, respectively), together with histologic correlation (ρ mucosal, .934; vascular, .938; P < .001 for both)., Conclusions: PICaSSO demonstrates good interobserver agreement across all levels of experience, providing excellent correlation with histology. Given the ability to discriminate subtle endoscopic features, PICaSSO may be applied to refine stratified treatment paradigms for UC patients., (Copyright © 2018 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Endoscopic inflammation and healing are important therapeutic endpoints in ulcerative colitis (UC). We developed and validated a new electronic virtual chromoendoscopy (EVC) score that could reflect the full spectrum of mucosal and vascular changes including mucosal healing in UC., Methods: Eight participants reviewed a 60-minute training module outlining 3 different i-SCAN modes demonstrating the entire spectrum of inflammatory mucosal and vascular changes in UC. Performance characteristics in endoscopic scoring and predicting the histologic inflammation with EVC (i-SCAN) by using 20 video clips before (pre-test) and after (post-test) were evaluated. Exploratory univariate factor analysis was performed on Paddington International Virtual Chromoendoscopy Score (PICaSSO) covariates for mucosal and vascular score separately. Subsequently, a proportional odds logistic regression model for the prediction of histologic scores was analyzed., Results: The interobserver agreement for Mayo endoscopic score in the pre-test (κ = .85; 95% CI, .78-.90) and the post-test (κ = .85; 95% CI, .77-.90) evaluation were very good. This was also true for the Ulcerative Colitis Endoscopic Index of Severity in the pre-test and post-test score interobserver agreement (κ = .86; 95% CI, .77-.92; and κ = .84; 95% CI, .75-.91, respectively). The interobserver agreement of the PICaSSO endoscopic score was very good in the pre-test and post-test evaluations (κ = .92; 95% CI, .87-.96; and κ = .89; 95% CI, .84-.94, respectively). The accuracy of the overall PICaSSO in assessing histologic abnormalities and inflammation by Harpaz score was 57% (95% CI, 48%-65%), by Robarts Histological Index 72% (95% CI, 64%-79%), and by the extent, chronicity, activity, plus system (full spectrum of histologic changes) 83% (95% CI, 76%-88%)., Conclusions: The EVC score "PICaSSO" showed very good interobserver agreement. The new EVC score may be used to define the endoscopic findings of mucosal and vascular healing in UC and reflected the full spectrum of histologic changes., (Copyright © 2017 American Society for Gastrointestinal Endoscopy. All rights reserved.)

Background and study aim  The I-SCAN optical enhancement (OE) system with magnification is a recently introduced combination of optical and digital electronic virtual chromoendoscopy, which enhances mucosal and vascular details. The aim of this pilot study was to investigate the use of I-SCAN OE in the assessment of inflammatory changes in ulcerative colitis (UC). Patients and methods  A total of 41 consecutive patients with UC and 9 control patients were examined by I-SCAN OE (Pentax Medical, Tokyo, Japan). Targeted biopsies of the imaged areas were obtained. A new optical enhancement score focusing on mucosal and vascular changes was developed. The diagnostic accuracy of I-SCAN OE was calculated against histology using two UC histological scores - Robarts Histopathology Index (RHI) and ECAP ( E xtent, C hronicity, A ctivity, P lus additional findings). Results  The overall I-SCAN OE score correlated with ECAP ( r  = 0.70; P  < 0.001). The accuracy of the overall I-SCAN OE score to detect abnormalities by ECAP was 80 % (sensitivity 78 %, specificity 100 %). I-SCAN OE vascular and mucosal scores correlated with ECAP ( r  = 0.65 and 0.71, respectively; P  < 0.001). The correlation between overall I-SCAN OE score and RHI was r  = 0.61 ( P  < 0.01), and the accuracy to detect abnormalities by RHI was 68 % (sensitivity 78 %, specificity 50 %). The majority of patients with Mayo 0 had abnormalities on I-SCAN OE. Conclusion  In UC, the new I-SCAN OE technology accurately identified mucosal inflammation, and correlated well with histological scores of chronic and acute changes., Competing Interests: Competing interests: Dr. Iacucci has received an unrestricted research grant from Pentax USA., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background and Study Aim: The differential diagnosis of ulcerative colitis from Crohn's disease is of pivotal importance for the management of inflammatory bowel diseases, as both entities involve specific therapeutic management strategies. Confocal laser endomicroscopy (CLE) allows on-demand, in vivo characterization of architectural and cellular details during endoscopy. The aim of this study was to assess the efficacy of CLE to differentiate between ulcerative colitis and Crohn's disease., Patients and Methods: This was a prospective study involving consecutive patients with a well-established diagnosis of ulcerative colitis or Crohn's disease who underwent colonoscopy with fluorescein-aided confocal imaging., Results: Overall, 79 patients were included (40 Crohn's disease, 39 ulcerative colitis). CLE findings in patients with Crohn's disease, showed significantly more discontinuous inflammation (87.5 % vs. 5.1 %), focal cryptitis (75.0 % vs. 12.8 %), and discontinuous crypt architectural abnormality (87.5 % vs. 10.3 %) than in ulcerative colitis (P < 0.0001). Conversely, ulcerative colitis was associated with severe, widespread crypt distortion (87.2 % vs. 17.5 % in Crohn's disease), decreased crypt density (79.5 % vs. 22.5 %), and frankly irregular surface (89.7 % vs. 17.5 %; P < 0.0001 for all comparisons). Statistically significant differences were not seen for heavy, diffuse lamina propria cell increase or mucin preservation. No granulomas were visible. Based on these findings, a CLE scoring system was developed that revealed excellent accuracy (93.7 %) when compared with the historical clinical diagnosis and the histopathological gold standard., Conclusions: CLE could visualize several disease-specific microscopic features, which are conventionally used in standard histopathology to differentiate between ulcerative colitis and Crohn's disease. However, because of the limited penetration depth of CLE, submucosal details or granulomas were not visible. The new scoring system may allow in vivo diagnosis of ulcerative colitis or Crohn's disease. Trial registered at ClinicalTrials.gov: NCT 02238665., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Increased cell shedding with gap formation and local barrier dysfunction can be identified endomicroscopically in the terminal ileum of patients with inflammatory bowel disease. We aim to evaluate whether these changes are also present in the duodenum of patients with inflammatory bowel disease., Methods: Fifteen patients with Crohn's disease (CD), 10 patients with ulcerative colitis (UC), and 10 controls underwent fluorescein-aided confocal laser endomicroscopy (CLE). CLE was performed on macroscopically normal antral and duodenal (D1, D2, D3, D4) mucosa. Representative CLE images were prospectively analyzed. Images were scored for the number of epithelial gaps, cell shedding, and the degree of fluorescein leakage into the intestinal lumen., Results: Both CD and UC patients had significantly more epithelial gaps, epithelial cell shedding, and leakage of fluorescein into the duodenal lumen than controls. The degree of cell shedding and epithelial gap formation was similar in CD and UC patients. In all cases, macroscopic endoscopic appearances of the duodenum were normal, and conventional histological analysis showed a mild nonspecific duodenitis in 7 of 15 patients with CD. Patients with UC had a histologically normal duodenum. Gap formation, cell shedding, and fluorescein leakage was similar in CD with active compared with inactive disease, except for D2 shedding., Conclusions: CLE can detect epithelial damage and barrier loss in the duodenum of CD and UC patients that is not apparent on conventional endoscopy or histology.

Background: Increased vascular permeability and angiogenesis play a crucial role in the pathogenesis of inflammatory bowel disease (IBD). Aim was to determine whether computed virtual chromoendoscopy has the potential to enhance assessment of disease severity and extent in patients with mild or inactive IBD in comparison to high-definition white-light endoscopy., Methods: Consecutive patients with IBD were randomly assigned at a 1:1 ratio to undergo colonoscopy with high-definition white light (group A) or computed virtual chromoendoscopy (group B). The mucosal vascular pattern and any mucosal abnormalities were recorded. Subsequent to endoscopic characterization targeted, biopsies were obtained from every segment for subsequent histopathological analysis of disease activity., Results: Overall, 100 patients were screened to participate in this study of whom 78 patients (high-definition white light, n = 39; computed virtual chromoendoscopy, n = 39) completed the study protocol thereby matching the previously calculated sample size. Average duration of the examination was 18 minutes in group A and 20.5 minutes in group B that was not statistically significant. When comparing the endoscopic prediction of inflammatory extent and activity with the histological results, an overall agreement of 48.71% and 53.85% (group A) and 92.31% and 89.74% (group B) was found, respectively. These differences were statistically significant (P = 0.0009 and P = 0.066)., Conclusions: This study indicates that computed virtual chromoendoscopy significantly improves the diagnosis of the severity and extent of mucosal inflammation in patients with IBD. This newly developed imaging technique may therefore have important implications for therapeutic interventions in patients with IBD.

Chromoendoscopy with methylene blue or indigo carmine significantly increases the diagnostic yield of finding intraepithelial neoplasia in patients with longstanding colitis. The number needed to treat is 14 for panchromoendoscopy to identify 1 additional patient with dysplasia. Chromoendoscopy can greatly facilitate the identification of flat lesions harboring intraepithelial neoplasia. Chromoendoscopy can guide biopsies and clearly reduces the amount of biopsies that are needed per patient. Magnifying endoscopy or CLE are additional techniques, which can be used in conjunction with chromoendoscopy to further reduce the amount of biopsies and to further increase the diagnostic yield. Chromoendoscopy is an established clinical procedure and recommended by many gastroenterological societies for surveillance of patients with longstanding ulcerative colitis. Thus, intravital staining should be an essential part of the diagnostic armamentarium of every colonoscopist.

Advanced imaging technologies are enabling targeted biopsies or endoscopic resections due to better visualization of the mucosal architecture. This new concept of 'smart biopsies' is in particular important for patients with higher risk for development cancer (e.g. ulcerative colitis) but can also be beneficial for screening purposes. This short review will focus on new imaging modalities like chromoendoscopy, digital chromoendoscopy, high-definition endoscopy and confocal laser endomicroscopy in the lower GI tract which will be crucial in the future to detect colorectal neoplasia earlier then before., (Copyright © 2010 S. Karger AG, Basel.)

Background: The diagnosis of intraepithelial neoplasia is pivotal for ongoing clinical management decisions in ulcerative colitis. Previous studies have compared the diagnostic yield of endomicroscopy with conventional "white light" endoscopy and hence the overall objective increase of endomicroscopy targeted biopsies as compared to chromoscopy guided alone is not apparent., Aims: We performed a prospective randomised controlled study to compare the diagnostic yield of intraepithelial neoplasia and cancer in patients undergoing ulcerative colitis screening using chromoscopy assisted endomicroscopy (group A) versus pan-colonic chromoscopy assisted colonoscopy (group B)., Methods: Patients were randomised in a 1:1 ratio to undergo screening colonoscopy using either chromoscopic endomicroscopy or chromoscopy alone with targeted biopsies. Circumscribed lesions were characterised using endomicroscopy and chromoscopy with pit pattern analysis. Targeted biopsies in addition to conventional 10 cm quadrantic biopsies were taken. Primary outcome addressed the number of intraepithelial neoplasias detected in each group., Results: Endomicroscopy targeted biopsies significantly increased the yield of intraepithelial neoplasia as compared to pan-chromoscopy and biopsy alone (p<0.001) and also increased the yield of high-grade dysplastic lesions (p<0.001). Endomicroscopy targeted biopsies increased the diagnostic yield of intraepithelial neoplasia as compared to chromoscopy guided biopsies alone by 2.5-fold., Conclusions: This is the first randomised controlled study to show the true clinical benefit of endomicroscopy for the in vivo detection and characterisation of intraepithelial neoplasia in chronic ulcerative colitis surveillance colonoscopy. Endomicroscopy with targeted biopsy may potentially be the "gold standard" for the detection of intraepithelial neoplasia in ulcerative colitis.

Background and Aims: Because of the large number of biopsy specimens, surveillance colonoscopy in ulcerative colitis (UC) is currently time consuming and significant flat lesions still may be missed. In this study we assessed the value of combined chromoscopy and endomicroscopy for the diagnosis of intraepithelial neoplasias in a randomized controlled trial., Methods: A total of 161 patients with long-term UC in clinical remission were randomized at a 1:1 ratio to undergo conventional colonoscopy or chromoscopy with endomicroscopy. Eight patients were excluded because of insufficient bowel preparation. In the conventional colonoscopic group (n = 73), random biopsy examinations and targeted biopsy examinations were performed. In the endomicroscopy group (n = 80), circumscribed mucosal lesions were identified by chromoscopy and evaluated for targeted biopsy examination by endomicroscopy. The primary outcome analysis was based on the detection of neoplasias., Results: By using chromoscopy with endomicroscopy, 4.75-fold more neoplasias could be detected (P = .005) than with conventional colonoscopy, although 50% fewer biopsy specimens (P = .008) were required. If only circumscribed lesions would have been biopsied in the first group, the total number of biopsy specimens could have been reduced by more than 90%. A total of 5580 confocal endomicroscopic images from 134 circumscribed lesions were compared with histologic results. The presence of neoplastic changes could be predicted by endomicroscopy with high accuracy (sensitivity, 94.7%; specificity, 98.3%; accuracy, 97.8%)., Conclusions: Endomicroscopy based on in vivo histology can determine if UC lesions identified by chromoscopy should undergo biopsy examination, thereby increasing the diagnostic yield and reducing the need for biopsy examinations. Thus, chromoscopy-guided endomicroscopy may lead to significant improvements in the clinical management of UC.

The newly developed high-resolution and magnification endoscopes offer features that allow more and new mucosal details to be seen. They are commonly used in conjunction with chromoendoscopy. The analysis of mucosal surface details is beginning to resemble histologic examination. More accurate recognition of small flat and depressed neoplastic lesions is possible. Endoscopic prediction of neoplastic and nonneoplastic tissue is possible by analysis of surface architecture of the mucosa, which influences the endoscopic management. For the diagnosis of flat adenomas, chromoendoscopy should be a part of the endoscopist's armamentarium. In inflammatory bowel disease, chromoendoscopy can be used for patients with long-standing UC to unmask flat intraepithelial neoplasia and is likely to become the new standard method for surveillance colonoscopy in the near future. The new detailed images seen with magnifying chromoendoscopy are the beginning of a new era in which advances in optical development, such as confocal endomicroscopy, allow a unique look at detailed cellular structures.

Background & Aims: Timely diagnosis of intraepithelial neoplasias (IN) and colitis-associated colon carcinomas (CRC) is crucially important for the treatment of ulcerative colitis (UC). We performed a randomized, controlled trial to test whether chromoendoscopy (CE) might facilitate early detection of IN and CRC in UC., Methods: A total of 263 patients with long-standing UC (>or=8 years) were screened for potential inclusion in the study, 165 of whom were randomized at a 1:1 ratio to undergo conventional colonoscopy or colonoscopy with CE using 0.1% methylene blue. Five mucosal biopsy specimens were taken every 10 cm between the rectum and cecum. Circumscript lesions in the colon were evaluated according to a modified pit pattern classification., Results: In the CE group, there was a significantly better correlation between the endoscopic assessment of degree (P = 0.0002) and extent (89% vs. 52%; P < 0.0001) of colonic inflammation and the histopathologic findings compared with the conventional colonoscopy group. More targeted biopsies were possible, and significantly more IN were detected in the CE group (32 vs. 10; P = 0.003). Using the modified pit pattern classification, both the sensitivity and specificity for differentiation between non-neoplastic and neoplastic lesions were 93%., Conclusions: Based on our prospective randomized trial, CE permits more accurate diagnosis of the extent and severity of the inflammatory activity in UC compared with conventional colonoscopy. In addition, CE with methylene blue is a novel tool for the early detection of IN and CRC in patients with UC. These findings have important implications for medical and surgical interventions.