BACKGROUND:Patients with longstanding ulcerative colitis undergo regular dysplasia surveillance because they have an increased colorectal cancer risk. Autofluorescence imaging and chromoendoscopy improve dysplasia detection. The aim of this study was to determine whether autofluorescence imaging should be further studied as an alternative method for dysplasia surveillance in patients with longstanding ulcerative colitis. METHODS:This prospective, international, randomised controlled trial included patients from an ulcerative colitis-dysplasia surveillance cohort from five centres in the Netherlands and the UK. Eligible patients were aged 18 years or older who were undergoing dysplasia surveillance after being diagnosed with extensive colitis (Montreal E3) at least 8 years before study start or with left-sided colitis (Montreal E2) at least 15 years before study start. Randomisation (1:1) was minimised for a previous personal history of histologically proven dysplasia and concomitant primary sclerosing cholangitis. The coprimary outcomes were the proportion of patients in whom at least one dysplastic lesion was detected and the mean number of dysplastic lesions per patient. The relative dysplasia detection rate, calculated as the ratio of the detection rates by autofluorescence imaging and chromoendoscopy, needed to be more than 0·67 (using an 80% CI) for both primary outcomes to support a subsequent large non-inferiority trial. Outcomes were analysed on a per-protocol basis. The trial is registered at the Netherlands Trial Register, number NTR4062. FINDINGS:Between Aug 1, 2013, and March 10, 2017, 210 patients undergoing colonoscopy surveillance for longstanding ulcerative colitis were randomised for inspection with either autofluorescence imaging (n=105) or chromoendoscopy (n=105). Dysplasia was detected in 13 (12%) patients by autofluorescence imaging and in 20 patients (19%) by chromoendoscopy. The relative dysplasia detection rate of autofluorescence imaging versus chromoendoscopy for the proportion of patients with ulcerative colitis with at least one dysplastic lesion was 0·65 (80% CI 0·43-0·99). The mean number of detected dysplastic lesions per patient was 0·13 (SD 0·37) for autofluorescence imaging and 0·37 (1·02) for chromoendoscopy (relative dysplasia detection rate 0·36, 80% CI 0·21-0·61). Adverse events were reported for two patients in the autofluorescence imaging group (one patient had intraprocedural mild bleeding, and one patient had abdominal pain) and for three patients in the chromoendoscopy group (two patients had intraprocedural mild bleeding, and one patient had perforation). INTERPRETATION:Autofluorescence imaging did not meet criteria for proceeding to a large non-inferiority trial. Therefore, existing autofluorescence imaging technology should not be further investigated as an alternative dysplasia surveillance method. FUNDING:Olympus Europe and Olympus Keymed.

BACKGROUND AND AIMS:Patients with longstanding ulcerative colitis have an increased risk for developing colorectal cancer (CRC). Although the risk for ulcerative colitis is well-established, for Crohn's disease data are contradictory. This study aimed to determine the number of patients with Crohn's disease with dysplasia who are undergoing surveillance and to assess the diagnostic accuracy of chromoendoscopy (CE) combined with integrated confocal laser endomicroscopy (iCLE) for differentiating dysplastic versus nondysplastic lesions.METHODS:Patients with longstanding Crohn's colitis undergoing surveillance colonoscopy were included in this multicenter, prospective, cohort study. Surveillance was performed with CE, and lesions were assessed with iCLE for differentiation. All lesions were removed and sent for pathology as the reference standard.RESULTS:Between 2010 and 2014, a total of 61 patients with Crohn's colitis were included in 5 centers. Seventy-two lesions, of which 7 were dysplastic, were detected in 6 patients (dysplasia detection rate 9.8%); none included high-grade dysplasia or cancer. Combined CE with iCLE for differentiating neoplastic from nonneoplastic lesions had accuracy of 86.7% (95% confidence interval [CI], 78.1-95.3), sensitivity of 42.9% (95% CI, 11.8-79.8), and specificity of 92.4% (95% CI, 80.9-97.6). For CE alone, this was 80.3% (95% CI, 70.7-89.9), 28.6% (95% CI, 5.1-69.7), and 86.4% (95% CI, 80.9-97.6). The study terminated early because of frequent failure of the endoscopic equipment.CONCLUSIONS:This study shows a low incidence of dysplastic lesions found during surveillance colonoscopy in patients with longstanding extensive Crohn's colitis. The accuracy of both CE alone and CE in combination with iCLE was relatively good, although the sensitivity for both was poor. Because of frequent equipment failure, iCLE has limited applicability in daily practice as a surveillance strategy.

BACKGROUND AND STUDY AIMS:Endoscopic optical diagnosis can potentially replace histopathological evaluation of small colorectal lesions. The aim of this study was to evaluate diagnostic performance of WavSTAT, a novel system for automatic optical diagnosis based on laser-induced autofluorescence spectroscopy.PATIENTS AND METHODS:Consecutive patients who were scheduled for colonoscopy were included in the study. Each detected lesion with a size of ≤ 9 mm was differentiated using high resolution endoscopy (HRE) by the endoscopist, who then reported this as a low or high confidence call. Thereafter, all lesions were analyzed using WavSTAT. Histopathology was used as the reference standard. The primary outcome measures were the accuracy of WavSTAT to differentiate between adenomatous and nonadenomatous lesions, and the accuracy of an algorithm combining HRE (lesions differentiated with high confidence) and WavSTAT (all remaining lesions). The secondary outcome measure was the accuracy of on-site recommended surveillance intervals.RESULTS:At total of 87 patients with 207 small colorectal lesions were evaluated. Accuracy and negative predictive value of WavSTAT were 74.4 % and 73.5 %, respectively. The corresponding figures for the algorithm were 79.2 % and 73.9 %, respectively. Accuracy of on-site recommended surveillance interval was 73.7 % for WavSTAT alone and 77.2 % for the algorithm of HRE and WavSTAT.CONCLUSIONS:Both accuracy of WavSTAT alone and the algorithm combining HRE with WavSTAT proved to be insufficient for the in vivo differentiation of small colorectal lesions, and do not fulfill American Society for Gastrointestinal Endoscopy performance thresholds for assessment of diminutive lesions. Future studies should assess whether combining WavSTAT with more advanced imaging techniques could result in a higher accuracy.Netherlands Trial Registry (NTR 3235).

Background and aim: This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It addresses the choice amongst regimens available for cleansing the colon in preparation for colonoscopy.Methods: This Guideline is based on a targeted literature search to evaluate the evidence supporting the use of bowel preparation for colonoscopy. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was adopted to define the strength of recommendation and the quality of evidence.Results: The main recommendations are as follows. (1) The ESGE recommends a low-fiber diet on the day preceding colonoscopy (weak recommendation, moderate quality evidence). (2) The ESGE recommends a split regimen of 4L of polyethylene glycol (PEG) solution (or a same-day regimen in the case of afternoon colonoscopy) for routine bowel preparation. A split regimen (or same-day regimen in the case of afternoon colonoscopy) of 2L PEG plus ascorbate or of sodium picosulphate plus magnesium citratemay be valid alternatives, in particular for elective outpatient colonoscopy (strong recommendation, high quality evidence). In patients with renal failure, PEG is the only recommended bowel preparation. The delay between the last dose of bowel preparation and colonoscopy should be minimized and no longer than 4 hours (strong recommendation, moderate quality evidence). (3) The ESGE advises against the routine use of sodium phosphate for bowel preparation because of safety concerns (strong recommendation, low quality evidence).

BACKGROUND AND STUDY AIMS:Novel imaging techniques need to be evaluated for their ability to improve the detection of polyps. Critical appraisal of reported studies reveals remarkable differences in study designs, despite their similar objectives. The aim of the current study was to compare frequently used study designs for their required sample size to detect relevant differences in polyp detection rates. PATIENTS AND METHODS:Three commonly reported study designs were compared: design 1, the parallel randomized design; design 2, the randomized cross-over design with direct removal of polyps; and design 3, the randomized cross-over design without direct removal of polyps. A total of five different scenarios were analyzed per study design, representing a variety of clinical settings. Each scenario was repeated 1000 times for each study design and the sample size that produced a significant result per study design in each scenario was recorded. RESULTS:In many scenarios, study design 1 required 10-15 times more patients to reach the same statistical power of 80% compared with study design 2. Further reductions in sample size could be achieved when study design 3 was used, although this design is limited by its impracticality. CONCLUSIONS:The randomized parallel design requires a larger sample size to achieve equivalent power to the cross-over design. Researchers should carefully consider whether the latter design could be used instead, as it requires a lower number of subjects, although it may be more cumbersome for patients, endoscopists, and researchers.

BACKGROUND & AIMS: When small colorectal lesions are accurately characterized, adenomas can be removed and discarded without formal histopathology analysis. Previous studies in an academic setting showed that many lesions can be managed accurately on the basis of their endoscopic image (optical diagnosis). We performed a prospective study to assess the accuracy of optical diagnosis of small colorectal polyps in a nonacademic setting (the DISCOUNT trial) by using high-resolution endoscopy (HRE) and narrow-band imaging (NBI). METHODS: During colonoscopy, 1 of 3 nonacademic endoscopists characterized small lesions and declared whether this was done with low or high confidence. In cases of high confidence, the endoscopists decided whether lesions should be removed and discarded or whether they could be left in situ. A surveillance interval was then recommended on-site. RESULTS: Of 215 patients in the study, 108 were found to have 281 small lesions. Of these lesions, 231 were characterized with high confidence by using HRE or NBI; the level of corresponding sensitivity was 77.0% (95% confidence interval, 68.4-83.8), and specificity was 78.8% (95% confidence interval, 70.6-85.2). Of these lesions, 164 were assigned for removal, and 67 were assigned to remain in situ, including 9 adenomas. In 54 patients, a surveillance interval could be recommended on-site that was in line with Dutch guidelines for 44 patients. CONCLUSIONS: Even though many lesions were characterized by HRE or NBI with high confidence, optical diagnosis in a nonacademic setting proved to be disappointing, with a sensitivity of 77.0% and a specificity of 78.8%. Many lesions were accurately assigned to be removed or remain in situ, although few adenomas were assigned to remain in situ. Also, 19% of on-site recommendations for a surveillance interval proved to be inaccurate.

WavSTAT is an optical biopsy system that can aide endoscopists in differentiation of colorectal lesions. Accurate differentiation of small colorectal lesions can result in removal of these lesions without formal histopathology making colonoscopy more efficient and cost-effective. The laser light of the WavSTAT is absorbed by colonic tissue resulting in an autofluorescent return signal, which is subsequently analysed. Within seconds a 'non-adenomatous' or 'adenomatous' result is displayed on a screen. The WavSTAT can be particularly useful as an add-on technique for differentiation of colorectal lesions that the endoscopist differentiates with low confidence using white light (WL). The aim of the current study is to assess the sensitivity, specificity and accuracy of an algorithm combining WL and WavSTAT. In this algorithm, overall accuracy is defined by WL in high confidence lesions and by WavSTAT in low confidence lesions.

OBJECTIVES:Several advanced imaging techniques have been developed to improve differentiation of colorectal lesions. These techniques need to be assessed for both feasibility and accuracy in order to prove their value in daily clinical practice. The current study assessed the feasibility of probe-based confocal laser endomicroscopy (pCLE) in acquiring videos of sufficient quality. Furthermore, the accuracy of pCLE for the differentiation of colorectal lesions was assessed and compared with narrow-band imaging (NBI) and chromoendoscopy (CE). METHODS:Consecutive patients scheduled for surveillance colonoscopy at our centre were included. All procedures were performed by two expert colonoscopists, who previously participated in studies evaluating pCLE, NBI, and CE. All detected lesions during colonoscopy were differentiated real-time with NBI and CE for Kudo pit pattern. Lesions were also assessed real-time for vascular pattern intensity (VPI) during NBI. Subsequently, pCLE videos of each lesion were acquired and biopsies were taken for histopathology. All pCLE videos were assessed post-hoc for the percentage of time demonstrating sufficient image quality (i.e., depicting at least one crypt or vessel). Finally, pCLE videos were assessed post-hoc for diagnostic accuracy by two experts. RESULTS:A total of 154 lesions detected in 64 patients were included. Accuracy of Kudo pit pattern with NBI for predicting neoplasia (88.7%) was significantly better than accuracy of VPI (77.5%, P = 0.05) but not significantly different from CE (89.3%, P = 0.125). During pCLE, no histology was shown at all on the video in 19 lesions (12%). The mean time to acquire a pCLE video of the remaining 135 lesions was 50 seconds (s.d. 47) per lesion. The median percentage demonstrating sufficient quality per video was 40.5% (interquartile range 21.2-67.0). Accuracy of pCLE for both observers (66.7 and 71.9%) was significantly lower than accuracy of CE (P < 0.001) and NBI (P < 0.001). CONCLUSIONS:Video acquisition with pCLE could not be achieved in a small number of lesions. The majority of pCLE videos demonstrated insufficient quality in more than half of the time recorded. Moreover, post-hoc accuracy of pCLE was significantly lower in comparison with real-time accuracy of CE and NBI. Future research should assess whether further increase in experience could improve pCLE video acquisition and determine the real-time accuracy of pCLE for differentiating colorectal lesions.

Background: The endoscope-based confocal laser endomicroscopy (eCLE) system allows in vivo imaging of colorectal epithelium. Little is known about the learning curve for accurate interpretation of confocal images acquired with eCLE.Objective: To determine the learning curve of eCLE, its diagnostic accuracy, and the intra- and interobserver agreement for the differentiation of colorectal lesions.Design: Post hoc assessment of selected eCLE images.Setting: Academic centers.Patients: This study involved colonoscopic images from 47 patients.Main Outcome Measurements: Learning curve of eCLE, accuracy, and intraobserver and interobserver agreement.Methods: Three endoscopists received a short introduction to eCLE before evaluating 90 images. Observers assessed all eCLE images by using the Mainz classification. After each set of 30 images, the accuracy of each observer was assessed. The same procedure was repeated 6 months later by using the same set of images.Limitations: Post hoc assessment.Results: There were no significant changes between the first set of 30 images and the 2 consecutive sets (P = .08 and P = .180, respectively). The overall accuracy was 85.6%, 95.6%, and 92.2% for each observer. The kappa values of the intraobserver agreement were 0.68, 0.84, and 0.77 for each observer. The kappa value for interobserver agreement was 0.73 during the first and 0.72 during the second assessment.Conclusions: Accurate post hoc interpretation of eCLE confocal images can be learned quickly. High diagnostic accuracy was achieved by all 3 observers during the initial stage of the assessment, which remained high thereafter. Intra-and interobserver agreement was substantial for all 3 observers. Future studies should focus on the real-time assessment of eCLE images. (Gastrointest Endosc 2012;75:1211-7.)

When small colorectal lesions (<10mm) are accurately differentiated, recto-sigmoid hyperplastic polyps can be left in situ whereas adenomas are removed. Moreover, removed lesions can be dispensed without formal histopathology, making colonoscopy more efficient and cost-effective. Previous studies have shown that a high accuracy can be achieved for differentiation of small colorectal lesions using high-resolution endoscopy (HRE) and narrow-band imaging (NBI). These studies have all been performed in an expert setting, however. We proposed the current study to assess the real-time accuracy of HRE and NBI for differentiation of small colorectal lesions in a non-expert setting.

Aim A recent systematic review indicated that dysplasia present before restorative proctocolectomy is a predictor of subsequent dysplasia in the pouch. This prospective study was carried out to assess the prevalence of dysplasia in the ileal pouch in patients having RPC for ulcerative colitis with co-existing dysplasia in the operation specimen.Method Eligible patients were invited for a surveillance endoscopy. The afferent and blind efferent ileal loop, ileoanal pouch and rectal cuff were examined by standard endoscopy using a dye-spray technique with methylene blue. Mucosal abnormalities were biopsied and random biopsies were taken from the afferent and blind ileal loop, pouch and rectal cuff.Results Fourty-four patients (25 male, mean 49 years) underwent pouch endoscopy at a mean interval from RPC of 8.6 years. Dysplasia was detected in two (4.5%) patients. In one, low-grade dysplasia was found in the rectal cuff and in the other low-grade dysplasia was detected in random biopsies from the pouch and the efferent ileal loop.Conclusion This prospective pouch-endoscopy study detected dysplasia in < 5% of patients over nearly 10 years. The benefit of routine surveillance for dysplasia in the pouch is uncertain, as the significance of low-grade dysplasia in the pouch is not clear.

Background and aims: Probe-based confocal laser endomicroscopy (pCLE; Cellvizio, Mauna Kea Technologies, Paris, France) enables in vivo histology during colonoscopy and may allow endoscopists to make real-time diagnoses. A collaboration of five experts proposed a new pCLE classification for colonic use. The aim of this study was to assess interobserver agreement and accuracy of the new pCLE classification in the colon.Patients and methods: Eligible patients were prospectively investigated by pCLE. A subset of 13 pCLE video sequences was reviewed post hoc for the establishment of a new classification, which comprised three vessel categories and seven crypt categories. All five blinded observers then scored another set of 102 video sequences, using the new classification. Histopathology was used as a reference standard.Results: The interobserver agreements on vessel and crypt architecture were 'fair' with kappa values of 0.29 and 0.27, respectively. When the classification was reduced to neoplasia vs. non-neoplasia (i.e. vessel or crypt type 3), overall agreement became 'moderate' (kappa = 0.56). Overall sensitivity and specificity for predicting neoplasia was 66% and 83%, respectively. When all observers agreed (69% of videos), the corresponding figures became 80% and 95%.Conclusion: A new classification for pCLE in the colon had a 'moderate' interobserver agreement for differentiating neoplasia from non-neoplastic tissue in the colon. The overall accuracy (81%) for predicting neoplasia was acceptable and became excellent (94%) when all five observers agreed. Future research should focus on refinement and validation of the classification.

BACKGROUND & AIMS Endoscopic trimodal imaging (ETMI) is a novel endoscopic technique that combines high-resolution endoscopy (HRE), autofluorescence imaging (AFI), and narrow-band imaging (NBI) that has only been studied in academic settings. We performed a randomized, controlled trial in a nonacademic setting to compare ETMI with standard video endoscopy (SVE) in the detection and differentiation of colorectal lesions. METHODS The study included 234 patients scheduled to receive colonoscopy who were randomly assigned to undergo a colonoscopy in tandem with either ETMI or SVE. In the ETMI group (n=118), first examination was performed using HRE, followed by AFI. In the other group, both examinations were performed using SVE (n=116). In the ETMI group, detected lesions were differentiated using AFI and NBI. RESULTS In the ETMI group, 87 adenomas were detected in the first examination (with HRE), and then 34 adenomas were detected during second inspection (with AFI). In the SVE group, 79 adenomas were detected during the first inspection, and then 33 adenomas were detected during the second inspection. Adenoma detection rates did not differ significantly between the 2 groups (ETMI: 1.03 vs SVE: 0.97, P=.360). The adenoma miss-rate was 29% for HRE and 28% for SVE. The sensitivity, specificity, and accuracy of NBI in differentiating adenomas from nonadenomatous lesions were 87%, 63%, and 75%, respectively; corresponding values for AFI were 90%, 37%, and 62%, respectively. CONCLUSIONS In a nonacademic setting, ETMI did not improve the detection rate for adenomas compared with SVE. NBI and AFI each differentiated colonic lesions with high levels of sensitivity but low levels of specificity.

Endoscopic Tri-modal Imaging (ETMI) is a novel technique which combines high-resolution white light endoscopy (HRE), autofluorescence imaging (AFI) and narrow band imaging (NBI) and may improve the detection and differentiation of colonic lesions. ETMI has only been subjected to research in expert settings. This randomized controlled multi-centre study compared ETMI with standard video endoscopy (SVE) for the detection and differentiation of early colorectal neoplasia in a non-expert setting.

Narrow-band imaging (NBI) is a new imaging modality that may improve the effectiveness of endoscopic surveillance and screening. Two recent studies have compared NBI with white light endoscopy; one study demonstrated no difference in adenoma detection rate between the two imaging modalities, the other study demonstrated improved differentiation of lesions with NBI compared with white light endoscopy.

Colonoscopy has been accepted as a modality for colorectal screening and surveillance for several years now. It has been shown to have a high sensitivity in detecting gastrointestinal lesions, and also allows complete examination of the colon and rectum and removal of polyps at the time of detection, making it a suitable screening tool. The demand of screening colonoscopies has increased over recent years for several reasons [2]. Despite this increased use, few studies have looked at the impact of colonoscopy screening on the incidence and mortality of colorectal cancer in the general population.