Marietta Iacucci

Beyond white light: optical enhancement in conjunction with magnification colonoscopy for the assessment of mucosal healing in ulcerative colitis.

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 (Extent, Chronicity, Activity, Plus 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.

Combining Biologics in Inflammatory Bowel Disease and Other Immune Mediated Inflammatory Disorders

&NA; Current therapies used in the treatment of inflammatory bowel disease (IBD) are not effective in all patients. Biologic agents result in approximately 40% remission rates at 1 year in selected populations, prompting a growing interest in combining biologic therapy to improve outcomes. There are limited published data regarding the efficacy and safety of combination targeted therapy in IBD specifically, which include only 1 exploratory randomized control trial and 3 case reports or series. This review evaluates the published literature regarding this therapeutic paradigm in IBD and its extensive utilization in the treatment of other immune‐mediated inflammatory disorders. The combination of biologic therapies demonstrates variable degrees of efficacy and highlights some safety concerns, depending upon the agents used and the disease state treated. A trial (ClinicalTrials.gov Identifier: NCT02764762) combining vedolizumab and adalimumab is currently underway evaluating the effectiveness and safety of this approach in patients with Crohn’s disease, which should provide further insight into this treatment concept. While combination biologic therapy is an attractive strategy, the lack of consistent superior efficacy as well as safety concerns militates the need for further trials prior to its general application in IBD.

Real-time Interobserver Agreement in Bowel Ultrasonography for Diagnostic Assessment in Patients With Crohn’s Disease: An International Multicenter Study

Background The unavailability of standardized parameters in bowel ultrasonography (US) commonly used in Crohns disease (CD) and the shortage of skilled ultrasonographers are 2 limiting factors in the use of this imaging modality around the world. The aim of this study is to evaluate interobserver agreement among experienced sonographers in the evaluation of bowel US parameters in order to improve standardization in imaging reporting and interpretation. Methods Fifteen patients with an established diagnosis of CD underwent blinded bowel US performed by 6 experienced sonographers. Prior to the evaluation, the sonographers and clinical and radiological IBD experts met to formally define the US parameters. Interobserver agreement was tested with the Quatto method (s). Results All operators agreed on the presence/absence of CD lesions and distinguished absence of/mild activity or moderate/severe lesions in all patients. S values were moderate for bowel wall thickness (s = 0.48, P = n.s.), bowel wall pattern (s = 0.41, P = n.s.), vascularization (s = 0.52, P = n.s.), and presence of lymphnodes (s = 0.61, P = n.s.). Agreement was substantial for lesion location (s = 0.68, P = n.s.), fistula (s = 0.74, P = n.s.), phlegmon (s = 0.78, P = 0.04), and was almost perfect for abscess (s = 0.95, P = 0.02). Poor agreement was observed for mesenteric adipose tissue alteration, lesion extent, stenosis, and prestenotic dilation. Conclusions In this study, the majority of the US parameters used in CD showed moderate/substantial agreement. The development of shared US imaging interpretation patterns among sonographers will lead to improved comparability of US results among centers and facilitate the development of multicenter studies and the spread of bowel US training, thereby allowing a wider adoption of this useful technique.

Su1997 - Generation and Validation of New Confocal Laser Endomicroscopy Criteria for the Diagnosis of Low-Grade Dysplasia in Barrett's Esophagus

Introduction The diagnosis and interobserver agreement amongst pathologists for low-grade dysplasia in Barrett’s oesophagus (BO) is sub-optimal. Probe-based confocal laser endomicroscopy (pCLE) allows real-time histologic assessment of BO. pCLE criteria for high-grade dysplasia (HGD) are established, however criteria for low-grade dysplasia (LGD) are lacking. The aim of the study was to develop and validate novel diagnostic criteria for LGD in BO. Method In Phase I, one pathologist and one endoscopist expert in pCLE unblinded assessed 30 good quality pCLE videos (10 non-dysplastic BO, 10 LGD and 10 HGD) to identify criteria for LGD. These criteria were assessed blindly by these two investigators in an independent set of 25 videos (15 non-dysplastic BO and 10 LGD). Criteria with mean accuracy >80% and interobserver agreement κ >0.4 were taken forward. In Phase II, 6 endoscopists evaluated the criteria in an independent set of 37 videos (15 non-dysplastic BO and 22 LGD). The raters assessed each criterion separately and made an overall diagnosis. Sensitivity, specificity and interobserver agreement were calculated for each criterion and the overall diagnosis. A receiver operating characteristic (ROC) curve was constructed to evaluate the best cut-off to diagnose dysplasia. Results Of the initial set of 8 criteria, 6 achieved the agreement and accuracy thresholds in Phase I. These were: (1) dark non-round glands, (2) irregular gland shape, (3) lack of goblet cells, (4) variable degree of darkness with sharp cut-off, (5) variable cell size and (6) loss of nuclear polarity. In Phase II the interobserver agreement among the 6 endoscopists for the criteria ranged from fair (K=0.242; criterion 4) to substantial (K=0.637; criterion 2), with a substantial interobserver agreement for the overall diagnosis (κ=0.6). The best cut-off for LGD diagnosis was 3 positive criteria out of 6, which corresponded to a sensitivity and specificity of 81.6% and 67.6%, respectively and an area under the ROC curve of 0.860. The overall diagnosis had sensitivity and specificity of 77.2% and 72.2%, respectively an area under the ROC curve of 0.895. Conclusion We have developed and validated pCLE criteria for LGD in BO. The performance of these criteria compares favourably with the interobserver agreement among pathologists in a conventional histologic diagnosis. Disclosure of Interest None Declared

PWE-142 A 10-year review of abdominal tuberculosis experience in a single multi-ethnic hospital population

Introduction Tuberculosis (TB) carries significant morbidity. It is most commonly pulmonary but it can also affect the gastrointestinal (GI) tract (6% of total cases in UK). Abdominal tuberculosis (A-TB) is a rare disease which can present a unique diagnostic challenge mimicking various GI diseases. We reviewed a 10 year cumulative regional TB database to report results on this unusual condition. Method A retrospective review of patients diagnosed with A-TB between 2006 & 2016 in a single tertiary centre in South Birmingham covering a multi-ethnic urban population of ~7 50 000. A central surveillance database managed by Respiratory Physicians and Public Health England was used to identify patients with A-TB. We reviewed clinical data from electronic records including radiology, chemical pathology, histopathology, endoscopy databases, surgical notes and letters. Results Of 41 patients [M=22 (54%);mean age 42y (SD ±17y)] identified with A-TB, 17 (41%) were Pakistani, 6 (15%) were other Asian and 8 (19%) were Afro-Caribbean with no data on country of origin or ethnicity recorded for the remainder. Thirty three (80%) were residents of economically deprived areas of Birmingham which were among the 10% of most deprived constituencies in UK, with an overall lowest national decile of 1#.(# Index of multiple deprivation as per local council) The most frequently reported symptoms were abdominal pain (n=23; 56%), weight loss (n=17; 41%), fever (n=10; 24%) and vomiting (n=9; 22%). Twelve (29%) patients were first seen in the surgical clinic and 9 (22%) in a medical gastroenterology clinic. A-TB was confirmed on tissue biopsy in 24 (58%) of which 2 were post-bowel resection. Seventeen (41%) patients had positive cultures with full drug sensitivity and only 5 (12%) patients had polymerase chain reaction (PCR) tests. Eight patients (20%) had concurrent pulmonary TB. Thirty seven patients (90%) received full, successful treatment for A-TB. Conclusion Asian ethnicity and low socioeconomic status appear to be risk factors for A-TB in a single tertiary centre. Histological diagnosis at endoscopic or surgical biopsy is a reliable diagnostic tool for confirming TB. Both gastroenterologists and surgeons need to consider A-TB in their differentials, as once diagnosed, most are successfully treated. Disclosure of Interest None Declared

PTH-024 The role of probe confocal laser endomicroscopy with image enhanced endoscopy in characterisation and endoscopic resection of dysplastic lesions in inflammatory bowel diseasepatients

Introduction Detection, characterisation and therapeutic management of dysplastic lesions during surveillance colonoscopy in inflammatory bowel disease (IBD) can be a challenge. The recent SCENIC consensus has introduced a new terminology and concept “endoscopically resectable” when the distinct margins of a lesion could be identified. New endoscopic techniques and skills are required to recognise the margins reliably and assess the surrounding mucosa to plan endoscopic removal. We report our experience of the use of probe confocal endomicroscopy (pCLE) combined with electronic virtual (VCE) and dye chromoendoscopy (DCE) for management of challenging dysplastic lesions. Method IBD patients underwent surveillance colonoscopy using high definition (HD)-iSCAN (Pentax, Japan) VCE and DCE in combination with pCLE (Cellvizio,France). pCLE was applied following injection of fluorescein 5% 10 ml to assess the histological features of the lesion, the margins and the mucosa surrounding the colonic lesion. Biopsies eventually proved dysplasia or SSA of the colonic lesions. The study was approved by the Conjoint Health Services Research Ethics Board of the University of Calgary. All patients gave informed consent. Results Seven patients with IBD and disease duration of ≥8 years (mean age 55 years; 6 male, UC=4 CD=3) were prospectively included. They underwent surveillance colonoscopy using HD–iSCAN (Pentax EC-3940Fi; Japan). When a colonic lesion was detected, selective iSCAN -VCE was performed with or without DCE (five out of seven had DCE) with methylene blue 1% to characterise the surface, vascular pattern and the margins of the lesion. Each of the 7 patients had non polypoid colonic lesions, 4 were sessile (Paris Is) and 3 flat (IIa/IIb).All dysplastic lesions were diagnosed by pCLE and confirmed by histology. Four of them were amenable to endoscopic therapy and were successfully removed using endoscopic mucosal resection (EMR) en-block or piecemeal technique. Interestingly, one patient with multiple scattered ‘pseudopolyps’ had a 8 mm sessile pseudopolypoid lesion with a suspicious areas of SSA in the midst that was confirmed by pCLE. The endoscopic, endomicroscopic and histological findings of all the lesions were described in Table Conclusion This case series highlights the first successful use of pCLE in combination with VCE and DCE to predict, characterise and treat colonic neoplasia in IBD. pCLE may be an additional tool to aid the endoscopist in therapeutic management by deciding endoscopic resectability versus colectomy. Disclosure of Interest None Declared

Location and Kudo Pit Pattern Reflect Neoplastic Histology of Lesions Detected at Surveillance Colonoscopy in Inflammatory Bowel Disease

Introduction Effective colonoscopic surveillance of IBD benefit from having reliable predictors of neoplasia, since targeted biopsies and endoscopic resection are increasingly used as standard of practice. It is not clear whether Kudo pit patterns may be applicable in characterising IBD associated lesions. We aimed to identify the specific clinical and endoscopic features of colonic lesions which predict dysplasia in IBD. Method All lesions identified in a randomised study to determine the detection rates of neoplastic lesion (NL) in patients with long standing colitis in IBD ( NCT02098798) were included. NL were classified by the Paris classification, Kudo pit pattern, and by the Vienna classification. Univariate analysis was performed, and age, duration of disease, extra-intestinal manifestations,family or personal history of polyps/cancer, smoking, size of lesion, Paris classification, Kudo pit pattern, localization/extension were considered .Subsequently a multivariate logistic regression model analyses was created and analysed with candidate variables which had p values≤0.05 on univariate analysis. Results A total of 270 patients (55% men; median age 49y) were assessed by High Definition (n=90), virtual chromoendoscopy (n=90) or dye chromoendoscopy (n=90). Among 270 patients, ninety- one (33.7%) colonic dysplastic lesions and 1 adenocarcinoma were found. Sixty–two (68.8%) were polypoid and twenty-nine (31.8%) were non polypoid. Most of these lesions (92.3%) had Kudo pit pattern III-V. By univariate analysis, age- Odds Ratio (OR) 1.05 (95% CI:1.02–1.08), localization of the lesions in the right colon- OR 6.15 ( 95% CI: 3.12–12.12), Kudo pit pattern IIO, III-IV and V- OR 20.91 (95% CI:9.34–46.7) and Paris Is/Ip classification OR- 3.29 (95% CI 1.69–6.38) were associated with NL. Subsequently proportional multivariate logistic regression model for the prediction of colonic neoplasia confirmed that the endoscopic Kudo pit pattern- OR 21.50 (95% CI:86.5–60.1) and localization of the lesions in the right colon- OR 6.52 (95% CI:1.98–22.5) were predictors of colonic neoplasia at surveillance colonoscopy in IBD (Table). The overall accuracy of independent variables which predict neoplastic histological changes was 78% (95% CI 68%–88%), sensitivity 82% (95% CI 68%–97%), specificity 68% (95% CI 47%–89%), PPV 85% (95% CI 76%–95%) and NPV 64% (95% CI 42%–86%) which were significant in the multivariate analysis. Conclusion We demonstrated that the endoscopic Kudo pit pattern and localization of the lesions in the right colon were predictors of neoplasia in IBD. This may guide management strategy of NL detected at IBD surveillance. Disclosure of Interest M. Iacucci Conflict with: Pentax, O Akinola: None Declared, R Panaccione: None Declared, G Kaplan: None Declared, Y Leung: None Declared, K Novak: None Declared, C Seow: None Declared, X Gui: None Declared, S Urbanski: None Declared, P Minoo: None Declared, B Lethebe: None Declared, M Lowerison: None Declared, S Ghosh: None Declared

High-definition-iSCAN virtual chromoendoscopy has high sensitivity and specificity for the diagnosis of eosinophilic esophagitis

Background and study aims  A major challenge in eosinophilic esophagitis (EoE) is disease recognition during endoscopy as there are no pathognomonic findings. We aimed to determine the utility of high-definition (HD) iSCAN virtual chromoendoscopy (VC) in diagnosis of EoE. Patients and methods  One hundred eighty-nine consecutive patients presenting with dysphagia or food bolus impaction were assessed using HD-iSCAN VC (Pentax, Japan) with biopsies from distal, mid, upper esophagus and from furrows where visible. Results  Of 189 patients, 45 (23.8 %, male = 29, median age 40y) had a histological diagnosis of EoE; 73.3 % of the patients were newly diagnosed. iSCAN endoscopic features of EoE were linear furrows (91 %), edema (77.8 %), rings or tracheal appearance (73.3 %), whitish exudates (26.6 %) and narrowing or stricture (5 %). One patient (2.2 %) had all 5 endoscopic features. Ten patients (22.2 %) had linear furrows, edema,rings or tracheal appearance and whitish exudates on iSCAN, with a positive predictive value (PPV) 100 % (95 % CI 69.1 %-100 %) and negative predictive value (NPV) 80.4 % (95 % CI 73.9 %-86 %). Thirteen patients (29 %) presented with linear furrows, edema and rings or tracheal appearance on iSCAN, with a PPV 100 % (95 % CI 75.3 %-100 %) and NPV 81.8 % (95 % CI 75.3 %-87.2 %). Six patients (13.3 %) had furrows and edema and 6 patients (13.3 %) had furrows and rings or tracheal appearance on iSCAN, with a PPV 100 % (95 % CI 54.1 %-100 %) and NPV 78.69 % (95 % CI 72 %-84.4 %), respectively. The sensitivity and specificity of HD-iSCAN endoscopy were 97.62 % (95 % CI 87.43 %-99.94 %) and 89.58 % (95 % CI 83.40 %-94.05 %). The accuracy of HD-iSCAN endoscopy was 92.47 % (95 % CI 87.67 %-95.56 %). Conclusion  HD-iSCAN endoscopy is sensitive and specific with good accuracy for EoE diagnosis. Linear furrows, edema and tracheal appearance were the most common findings and these 3 endoscopic features had a high predictive value for diagnosis of EoE.