Emmanouil Telakis

Comparison of high definition with standard white light endoscopy for detection of dysplastic lesions during surveillance colonoscopy in patients with colonic inflammatory bowel disease

Background:Dysplasia in colonic inflammatory bowel disease (IBD) is often multifocal and flat. High-definition (HD) colonoscopy improves adenoma detection rates by improving the ability to detect subtle mucosal changes. The utility of HD colonoscopy in dysplasia detection in patients with IBD has not been reported so far. We aimed to compare the yield of dysplastic lesions detected by standard definition (SD) white light endoscopy with HD endoscopy. Methods:A retrospective cohort study of patients with long-standing (>7 years) colonic IBD undergoing surveillance colonoscopy at Nottingham University Hospital was studied between September 2008 and February 2010. Details of diagnosis, duration of disease, and outcomes of the colonoscopy were collected from the endoscopy database, electronic patient records, and patient notes. Results:There were 160 colonoscopies (101 ulcerative colitis [UC] and 59 Crohns disease [CD]) in the SD group and 209 colonoscopies (147 UC and 62 CD) in the HD group. The groups were well matched for all demographic variables. Thirty-two dysplastic lesions (27 on targeted biopsy) were detected in 24 patients in the HD group and 11 dysplastic lesions (six on targeted biopsy) were detected in eight patients the SD group. The adjusted prevalence ratio of detecting any dysplastic lesion and dysplastic lesion on targeted biopsy was 2.21 (95% confidence interval [CI] 1.09–4.45) and 2.99 (95% CI 1.16–7.79), respectively, for HD colonoscopy. Conclusions:HD colonoscopy improves targeted detection of dysplastic lesions during surveillance colonoscopy of patients with colonic IBD in routine clinical practice. Randomized controlled studies are required to confirm these findings.

The combination of autofluorescence endoscopy and molecular biomarkers is a novel diagnostic tool for dysplasia in Barrett's oesophagus

Objective Endoscopic surveillance for Barretts oesophagus (BO) is limited by sampling error and the subjectivity of diagnosing dysplasia. We aimed to compare a biomarker panel on minimal biopsies directed by autofluorescence imaging (AFI) with the standard surveillance protocol to derive an objective tool for dysplasia assessment. Design We performed a cross-sectional prospective study in three tertiary referral centres. Patients with BO underwent high-resolution endoscopy followed by AFI-targeted biopsies. 157 patients completed the biopsy protocol. Aneuploidy/tetraploidy; 9p and 17p loss of heterozygosity; RUNX3, HPP1 and p16 methylation; p53 and cyclin A immunohistochemistry were assessed. Bootstrap resampling was used to select the best diagnostic biomarker panel for high-grade dysplasia (HGD) and early cancer (EC). This panel was validated in an independent cohort of 46 patients. Results Aneuploidy, p53 immunohistochemistry and cyclin A had the strongest association with dysplasia in the per-biopsy analysis and, as a panel, had an area under the receiver operating characteristic curve of 0.97 (95% CI 0.95 to 0.99) for diagnosing HGD/EC. The diagnostic accuracy for HGD/EC of the three-biomarker panel from AFI+ areas was superior to AFI− areas (p<0.001). Compared with the standard protocol, this panel had equal sensitivity for HGD/EC, with a 4.5-fold reduction in the number of biopsies. In an independent cohort of patients, the panel had a sensitivity and specificity for HGD/EC of 100% and 85%, respectively. Conclusions A three-biomarker panel on a small number of AFI-targeted biopsies provides an accurate and objective diagnosis of dysplasia in BO. The clinical implications have to be studied further.

Comparison of high definition with standard white light endoscopy for detection of dysplastic lesions during surveillance colonoscopy in patients with inflammatory bowel disease

Introduction Dysplasia in colonic inflammatory bowel disease (IBD) is often multifocal and flat, making it easy for significant lesions to be overlooked. Dye spraying the mucosal surface is believed to enhance visualisation of subtle mucosal abnormalities, but is cumbersome and messy and has poor uptake among endoscopists. High definition (HD) colonoscopy improves adenoma detection rates by improving the ability to detect subtle mucosal changes and is as good as chromoendoscopy in polyp detection. The utility of high definition colonoscopy in dysplasia detection in patients with IBD has not been reported so far. The authors aimed to compare the yield of dysplastic lesions detected by standard definition white light endoscopy (SD) with high definition endoscopy (HD). Methods Details of consecutive patients with long standing (>7 years) colonic IBD who underwent surveillance colonoscopy at Nottingham University Hospitals between September 2008 and February 2010 were extracted from the endoscopy database. Details of diagnosis, duration of disease and outcomes of the colonoscopy were then collected from the electronic patient records and patient notes. The colonoscopies were done at 2 sites, of which one had only HD systems and the other SD. SPSS v17 was used for the data analysis. Results 360 colonoscopies were done on 353 patients. There were 162 colonoscopies (102 UC and 60 CD) in the SD group and 208 colonoscopies (146 UC and 62 CD), in the HD group. The groups were well matched for mean age of patients, duration of disease, gender and number of biopsies taken. Table 1 gives information on the number and characterisation of dysplastic lesions detected. Table 1 PTH-061 Dysplastic lesions detected by standard and high definition colonoscopy Standard definition (n=162) High definition (n=208) p Value Number of lesions 15 30 NS Number of patients with dysplasia 12 23 NS Number of patients with HGD/cancer 1/2 2/5 NS Number of patients with lesions on targeted biopsy 6 22 <0.05 Number of flat lesions detected 2 10 <0.05 Conclusion HD colonoscopy is superior to SD colonoscopy in targeted detection of dysplastic lesions during surveillance colonoscopy of patients with colonic IBD in routine clinical practice. HD colonoscopy could facilitate endoscopic resection in these patients. Randomised controlled studies are required to confirm these findings.

PWE-032 Endoscopic mucosal resection (EMR) followed by adjuvant radiofrequency ablation (RFA) can result in better outcomes compared to EMR alone in patients with Barrett's early neoplasia (EN). A comparative study from a tertiary centre in the UK

Introduction RFA has shown efficacy in eradicating Barretts EN (high grade dysplasia (HGD) or intra-mucosal cancer (IMC)). To our knowledge, there are no studies directly comparing outcomes in patients with EN who undergo EMR alone vs EMR followed by RFA. The aim of this study was to assess the efficacy, safety and long term outcomes of adjuvant RFA in this setting. Methods We searched our prospective Barretts Oesophagus EMR database for patients who had EMR of lesions harbouring EN followed by RFA for eradication of residual Barretts mucosa between 2007 and 2008 as part of a multi-centre trial (intervention group). The control group included patients with similar lesions who had undergone EMR followed by surveillance of residual Barretts mucosa. The two groups were matched for any potential confounders to minimise bias. Results There were 13 patients in each group. Mean age in the EMR group and EMR+RFA group was 70 and 59 years, respectively. Both groups were equally matched in terms of male to female ration (12:1); length of circumferential Barretts mucosa; lesion Paris classification; mean lesion size; and resection type (Piecemeal or En-bloc). The mean duration of follow-up in the EMR group was 21 months compared to 32 months in the EMR+RFA group. The histological characteristics of lesions in both groups are shown in the table below (Abstract PWE-032 table.1). Overall, histological eradication of EN was achieved in eight (62%) patients in the EMR group and 13 (100%) in the EMR+RFA group at the last follow-up. Persistence or recurrence of EN and the need for further EMR during follow-up occurred in five patients (38%) in the EMR group (two of them had Oesophagectomy) compared to only one (8%) in the EMR+RFA group. One patient (8%) in the EMR group developed oesophageal stricture and no complications occurred in the other group.Abstract PWE-032 Table 1 Histological characteristics EMR group (n=13) EMR + RFA group (n=13) Pre-EMR lesion histology  HGD 10 (77%) 10 (77%)  IMC 3 (33%) 3 (33%) EMR specimen histology  HGD 6 (46%) 3 (33%)  IMC 7 (64%) 10 (77%)  Clearance at lesion base 13 (100%) 13 (100%)  Residual HGD post EMR 4 (31%) 4 (31%)  Residual LGD post EMR 1 (8%) 1 (8%) Conclusion These data suggest that adjuvant RFA in this setting can have a significant positive impact on the long term success rate of histological eradication of EN in Barretts Oesophagus as well as reducing the risk of recurrence of those lesions. It can reduce the need for subsequent EMRs and radical surgery with no safety concerns. The long duration of follow-up and control for confounders add significant validity to the results, despite the relatively small number of patients included. Competing interests S Sami: None declared, E Telakis: None declared, J Mannath: None declared, P Kaye: None declared, K Ragunath Grant/Research Support from: Olympus, Cook and Barrx medical.

PTU-192 Time: prospective study combining endoscopic trimodal imaging and molecular endpoints to risk stratify Barrett's oesophagus

Introduction Biomarkers have been proposed to improve risk stratification in Barretts oesophagus (BO), however molecular heterogeneity of BO can hamper detection of molecular changes in random biopsies. Use of Autofluorescence Imaging (AFI) within endoscopic Trimodal Imaging (ETMI) can improve dysplasia detection, but has high false positive rate. Aims of study were (a) validate biomarkers previously published in separate patient cohorts in single study (b) assess whether AFI can increase detection of biomarkers (c) combine ETMI and biomarkers to improve risk stratification of patients with BO. Methods Prospective European multicentre study. Each patient underwent ETMI with targeted biopsies on AFI positive (AFI+) areas and one AFI negative (AFI−) area, as well as random quadrantic biopsies. DNA content abnormalities (aneuploidy/tetraploidy); loss of heterozygosity (LOH) at 9p and 17p loci; RUNX3, HPP1 and p16 methylation; immunohistochemistry (IHC) for p53 and Cyclin A were tested on targeted biopsies. Each biomarker was correlated with the dysplasia and AFI status. Results 111 patients with 210 biopsy areas were included in the analysis (AFI+, n=120; AFI-, n=90). Univariate per-biopsy analysis showed that all biomarkers correlated with dysplasia (p<0.05), with exception of 9p LOH. Multivariate analysis showed that aneuploidy, p53 IHC and Cyclin A (3 biomarker panel) were independently associated with dysplasia with an AUC=0.93 (95% CI 0.88 to 0.98) for any dysplasia and AUC=0.95 (95% CI 0.89 to 1) for HGD/early cancer (EC). AFI positivity significantly correlated with aneuploidy, p16 methylation, cyclin A and p53 staining (p<0.05). After excluding dysplastic areas, aneuploidy (p=0.03) and p53 (p=0.04) staining retained statistical correlation with AFI positivity. Analysis of the 3 biomarker panel in patients with dysplasia showed significant biomarker enrichment in AFI+ compared to AFI- areas (p=0.001). Finally, 3 biomarker panel was used to predict prevalent dysplasia. Using a cut-off of ≥2 biomarkers, the panel when applied to AFI+ areas alone, showed sensitivity and specificity of 88% and 90% respectively for diagnosis of HGD/EC, and 64% and 96% respectively for diagnosis of any dysplasia, compared to overall histology. Conclusion AFI increases detection rate for molecular biomarkers. A panel of 3 molecular biomarkers on a small number of AFI targeted biopsies can efficiently predict the dysplasia status and potentially inform therapeutic management of patients with BE. Competing interests None declared.

Comparison of narrow band imaging with high resolution white light endoscopy for the assessment of non-steroidal anti-inflammatory drug induced gastroduodenal injury

Introduction The diagnosis of NSAID induced gastroduodenal injury is often associated with difficulties in determination of the degree of injury. The Lanza score and its many modifications are commonly used in clinical trials, but are considered subjective and susceptible to errors in interpretation. The aim of this study was to determine the inter-observer variability in assessing NSAID induced gastroduodenal injury among endoscopists with and without experience in narrow band imaging (NBI) using both high resolution white light endoscopy (HR-WLE) and NBI. Methods Corresponding NBI and HR-WLE images were taken during endoscopy from healthy volunteers taking different NSAID preparations. Six blinded endoscopists (three experts in NBI imaging) counted the number of ulcers, erosions and haemorrhagic lesions to derive a five point modified Lanza scale and evaluated image quality on a 10 point visual analogue score (VAS). Overall agreement and κ value with bias corrected 95% CIs using bootstrapping techniques were calculated to assess interobserver reliability. Results The inter-observer agreement (κ) with HR-WLE among all six endoscopists was 0.62 (95% CI 0.52 to 0.72), which improved significantly with NBI to 0.76 (95% CI 0.69 to 0.84, p=0.02). The inter-observer agreement among expert endoscopists with HR-WLE was ‘substantial’ (κ=0.75, 95% CI 0.63 to 0.87) and improved with NBI to ‘almost perfect agreement (κ=0.87, 95% CI 0.78 to 0.95, p=0.06) which almost reached statistical significance. The inter-observer agreement among non-expert endoscopists with HR-WLE was ‘moderate’ (κ=0.54, 95% CI 0.42 to 0.67) and significantly improved with NBI to ‘substantial’ (κ=0.72, 95% CI 0.60 to 0.82, p=0.02). Non-expert endoscopists found significantly higher number of mucosal haemorrhages on NBI images (p=0.03). VAS scores for NBI images were higher than HR-WLE for experts while the opposite was true for non-experts. VAS scores for NBI images were however consistently higher than HR-WLE when the paired images were presented side by side. Conclusion Inter-observer reliability between both expert and non-expert endoscopists for assessment of NSAID induced injury is better with NBI than HR-WLE images. NBI imaging improves the visualisation of mucosal haemorrhages especially in non-expert endoscopists.

* Reducing capsule endoscopy reading times: efficacy of new playback functions

Introduction Capsule endoscopy (CE) has proven to be a valuable tool in the evaluation of obscure GI bleeding, suspected Crohns disease, coeliac disease and polyposis syndromes. The reading time and interpretation of video capsule data is very time consuming given that, in total, more than 50,000 images have to be reviewed. Recently, Olympus capsule endoscopy software systems have been equipped with auto-speed adjusted, express view and overview functions. The aim of this study was to evaluate the new functions by analysing the diagnostic yield of CE and the reading time of the new playback features by comparing it with conventional analysing systems. Methods Data on 42 patients who underwent CE were obtained, and two experienced CE readers (>100 cases) analyzed the CE images independently using either the overview with express selected function or the overview with auto-speed adjusted function respectively. All CE videos were read blinded at 15 frames per second using the two new functions. The diagnostic yield was then compared to the conventionally read CE findings. All CE recording were done using the Olympus (Keymed UK) capsule endoscopy systems and read using the Olympus EndoCapsule software package. Results 42 patients (20 male, 22 female) with a mean age of 49.3(±21.2) years were included in the study. Clinically significant findings were found in 24/42 (60%) of patients. Using overview functions alone would have resulted in missing 6/24 (25%) clinically significant findings, while both express selected and auto-speed adjusted methods missed 1/24 (4%) clinically significant findings each. The average reading time for the auto-speed function plus overview was 35(±10) minutes and was significantly (p=0.01) more than that for express selected plus overview which was 20(±5) min. If the CE videos were read conventionally at 15 frames per second the average reading time based on the length of the recording would have been 47 (±14) min. Conclusion The diagnostic miss rate was high when overview functions alone were used. There was no significant difference in positive findings between auto-speed adjusted and express selected functions when used along with overview functions and the reading time using the new systems was significantly shorter than the conventional system. The new playback systems can efficaciously reduce reading times of CE with the express selected function reducing readings time significantly more than the auto-speed adjusted function.

* An interobserver agreement study of autofluorescence endoscopy in barrett's oesophagus among expert endoscopists

Introduction Autofluorescence imaging (AFI) is used as a Șred flag’ technique during Barretts surveillance to identify subtle abnormal lesions which are not evident in high resolution white light endoscopy (HRE). This technique was found to have significant false positive results, but the sensitivity remains high. The aim of this study was to assess the interobserver agreement in detecting dysplastic lesions and to assess the overall accuracy of AFI among expert endoscopists. Methods Anonymised AFI and HRE images were prospectively collected from patients undergoing Barretts surveillance and dysplasia work-up. The AFI images were presented on power point in random order, followed by corresponding HRE and AFI images in a second folder. Three expert endoscopists (>150 AF endoscopies) scored the work sheet on separate occasions after an automated training presentation. The interobserver agreement was calculated using κ values (bias corrected) and the accuracy was calculated with histology as gold standard. Results 74 sets of anonymised white light and AFI images were prospectively collected from 63 patients (48 males, mean age 69). The interobserver agreement for number of AF lesions noted was fair with a κ value of 0.39 (95% CI 0.28 to 0.52) for AFI images which improved significantly (p=0.04) to moderate κ (0.57 and 95% CI 0.44 to 0.7) when corresponding AFI and HRE images are presented side by side. The interobserver agreement for the quadrant with most significant AF lesion was moderate with a κ of 0.48 (95% CI 0.37 to 0.6) which improved (p=0.08) to substantial κ 0.62 (95% CI 0.50 to 0.72) when corresponding images were presented. The sensitivity for dysplasia detection was 0.75 (95% CI −0.68 to 0.81) and 0.84 (95% CI 0.78 to 0.89) using AFI images alone and using corresponding images respectively. Similarly, the specificity was 0.76 (95% CI 0.71 to 0.81) and 0.85 (95% CI 0.8 to 0.89). The overall accuracy of detecting dysplasia was 0.76 (95% CI 0.7 to 0.81) using AFI images alone and 0.85 (95% CI 0.79 to 0.89) using corresponding HRE and AFI images. Conclusion The interobserver agreement for dysplasia detection in Barretts oesophagus using AFI images alone is only moderate among expert endoscopists, although it improved with addition of HRE. The overall accuracy of dysplasia using AF imaging was reasonable. Better understanding and recognition of what constitutes an AF positive signal on the endoscopic images is needed to improve this technique.

Predictive factors for histological discrepancy between endoscopic biopsies and endoscopic mucosal resection specimens in Barrett's dysplasia/early neoplasia

Introduction Accurate diagnosis of high grade dysplasia (HGD) or early cancer (EC) is of paramount importance in the management of Barretts oesophagus. Endoscopic biopsies are the standard method for the diagnosis of HGD/EC but discrepancies have been reported between biopsies and endoscopic mucosal resection (EMR) specimens. The aim of this study was to investigate the predictive factors for histological discrepancy between endoscopic biopsies and EMR specimens. Methods Prospectively collected data on all EMRs performed for Barretts HGD or EC in our institution over a 4-year period were analyzed. Histology of pre-resection biopsies and EMR specimens was retrieved from pathology records. Cases with diagnostic discrepancies between biopsies and EMRs were compared with those without discrepancies. Multivariate linear regression analysis was used with size of lesion, endoscopic morphology, length of Barretts, number of targeted biopsies, age and sex of patients as predictive factors. Results 59 lesions from 57 patients (43 men, mean age: 67 ± 11.2) who underwent EMR were studied. Mean length of Barretts was 5.2 ± 3.4 cm (range 1–13) and the mean size of lesions was 15.5 ± 4.9 mm (range 7–30 mm). Elevated (Paris 0-Is or 0-IIa) lesions were observed in 31 (52.5%) and flat/depressed lesions (0-IIb or 0-IIc) in 28 (47.5%) of cases. The mean number of pre-resection targeted biopsies was 3.1 ± 1.01 (range 1–5). The ‘band and snare’ mucosectomy technique was used in 46 (78%) and the cap-assisted technique in 13 (22%) EMR cases. Post-EMR histological diagnosis was HGD in 22 (37.3%) and carcinoma in 37 (62.7%) cases. The histological discrepancy rate was 44% (26/59). EMR upgraded the histological diagnosis in 22 (37.3%) cases and downgraded it in 4 (6.8%) resections. On multivariate linear regression analysis, <3 targeted biopsies per lesion was the only independent predictive factor (p = 0.03) and was associated with 3.3-fold increase in histological discrepancy (OR = 3.3, 95% CI 1.1 to 9.9). Size of lesion, endoscopic morphology, length of Barretts, age and sex had no statistically significant effect. Conclusion Obtaining 3 or more targeted biopsies per lesion improves the histological correlation between endoscopic biopsies and EMR specimens in patients with Barretts early neoplasia.