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Background and Aims There are no agreed-on endoscopic signs for the diagnosis of villous atrophy (VA) in celiac disease (CD), necessitating biopsy sampling for diagnosis. Here we evaluated the role of near-focus narrow-band imaging (NF-NBI) for the assessment of villous architecture in suspected CD with the development and further validation of a novel NF-NBI classification. Methods Patients with a clinical indication for duodenal biopsy sampling were prospectively recruited. Six paired NF white-light endoscopy (NF-WLE) and NF-NBI images with matched duodenal biopsy sampling including the bulb were obtained from each patient. Histopathology grading used the Marsh-Oberhuber classification. A modified Delphi process was performed on 498 images and video recordings by 3 endoscopists to define NF-NBI classifiers, resulting in a 3-descriptor classification: villous shape, vascularity, and crypt phenotype. Thirteen blinded endoscopists (5 expert, 8 nonexpert) then undertook a short training module on the proposed classification and evaluated paired NF-WLE–NF-NBI images. Results One hundred consecutive patients were enrolled (97 completed the study; 66 women; mean age, 51.2 ± 17.3 years). Thirteen endoscopists evaluated 50 paired NF-WLE and NF-NBI images each (24 biopsy-proven VAs). Interobserver agreement among all validators for the diagnosis of villous morphology using the NF-NBI classification was substantial (κ = .71) and moderate (κ = .46) with NF-WLE. Substantial agreement was observed between all 3 NF-NBI classification descriptors and histology (weighted κ = 0.72-.75) compared with NF-WLE to histology (κ = .34). A higher degree of confidence using NF-NBI was observed when assessing the duodenal bulb. Conclusions We developed and validated a novel NF-NBI classification to reliably diagnose VA in suspected CD. There was utility for expert and nonexpert endoscopists alike, using readily available equipment and requiring minimal training. (Clinical trial registration number: NCT04349904.)

Background and Aims EMR of large (≥2 cm) nonpedunculated colorectal polyps (LNPCPs) is associated with high rates of recurrent/residual adenoma, possibly because of microadenoma left at the margin of resection. Data supporting this mechanism are required. We aimed to determine the incidence of residual microadenoma at the defect margin and base after EMR. Methods We performed a retrospective observational study of patients undergoing EMR of large LNPCPs with the lateral defect margin further resected using the EndoRotor device (Interscope Medical, Inc, Worcester, Mass, USA) after confirming no visible residual adenomatous tissue. Aspects of the defect base were also resected in selected patients. Patients underwent surveillance at 3 to 6 months. Results Resection of the normal defect margin was performed in 41 patients and of aspects of the base in 21 patients. Mean lesion size was 43.0 mm (range, 20-130). Microscopic residual lesion was detected in the margin of apparently normal mucosa in 8 cases (19%). In 7 cases this was an adenoma, and in 1 case a serrated lesion was found at the margin of a resected tubular adenoma. Microscopic residual lesion was detected at the base in 5 of 21 cases. Residual/recurrent adenoma was detected in 2 patients. Neither had residual microadenoma at the lateral margin or base detected after the primary resection. Conclusions Microscopic residual adenoma after wide-field EMR was detected in 19% of cases at the apparently normal defect margin and at the resection base in 5 of 21 cases. This study confirms the presence of residual microadenoma after resection of LNPCPs, providing evidence for the mechanism of recurrence.

Introduction Safe and effective endoscopic resection (ER) relies on the endoscopic diagnosis of large lesions to predict the risk of invasive cancer. However, a detailed evaluation of histopathological features and the molecular profile of the polypoid dysplastic mucosa to predict coexistent invasive neoplasm is not available. Methods: Data from endoscopic resection of colorectal superficial neoplastic lesions performed at a UK tertiary referral center (2011-2016) were analyzed. Lesions were assessed using magnification chromoendoscopy and narrow band imaging. A subset of these lesions containing high-grade dysplasia, intramucosal cancer or invasive cancer was identified and further subjected to a detailed histopathological analysis: endoscopic type, ulceration, distribution of high-grade dysplasia, dysplastic nuclear grade, presence and distribution of necrosis, and distribution of tumor-infiltrating lymphocytes (TIL). The two areas with the highest morphological grade were microdissected from each lesion, using 5μm FFPE sections. DNA extraction and next-generation sequencing using a human clinically relevant tumor panel (Qiagen, Hiden, Germany) of 24 genes were performed for each of these areas separately. Genetic abnormalities for each locus were categorized by genetic impact according to its severity (low/moderate/high/modifier) and allele frequency. Results: ER was performed for 418 large (≥20mm) colorectal superficial neoplastic lesions (mean size 55.2mm, range 20mm-160mm), 81% being laterally spreading tumors (LST). The proportions harboring an area of invasive cancer by morphological subtype were as follows: LST non-granular 30.8%; LST granular mixed-nodular type 12.3%; LST granular homogeneous type 0.9% and Is/Isp 11.4%. The histopathological genetic evaluation was available in 70 cases; a coexistent adenocarcinoma significantly correlated with dysplastic adenomatous mucosa featuring ulceration, mixed interface/interstitial TIL, multifocal high nuclear grade, infiltrative edges, and multifocal intraluminal necrosis. Multifocal intraluminal necrosis and high nuclear grade in the adjacent low-grade dysplastic mucosa were driven by cooperative genetic abnormalities of high-impact (FLT4), moderate impact (KRAS/NRAS for infiltrative edges, FLT4, TP53, ERBB2), and low impact (FGFR3, PDGFA). Conclusions The dysplastic stage of high-grade adenomatous polyps is characterized by multiple cooperative genetic mutations. A subset of these markers identify a risk of coexistent adenocarcinoma with a close correlation between genetic markers of angiogenesis (FLT4), receptor activation (RAS/ERBB2), genome maintenance (TP53) and stromal reaction (FGFR3, PDGFRA) with morphological features defined by high nuclear grade, intraluminal necrosis, and inflammatory stromal reaction.

Background and Aims Per-oral endoscopic myotomy (POEM) has shown promising safety and efficacy in short-term studies. However, long-term follow-up data are very limited. The aims of this study were to assess (1) clinical outcome of patients with a minimum post-POEM follow-up of 2 years and (2) factors associated with long-term clinical failure after POEM. Methods A retrospective chart review was performed that included all consecutive patients with achalasia who underwent POEM with a minimum follow-up of 2 years at 10 tertiary-care centers. Clinical response was defined by a decrease in Eckardt score to 3 or lower. Results A total of 205 patients (45.8% men; mean age, 49 years) were followed for a median of 31 months (interquartile range, 26-38 months). Of these, 81 patients (39.5%) had received previous treatment for achalasia before POEM. Clinical success was achieved in 98% (185/189), 98% (142/144), and 91% (187/205) of patients with follow-up within 6 months, at 12 months, and ≥24 months, respectively. Of 185 patients with clinical response at 6 months, 11 (6%) experienced recurrent symptoms at 2 years. History of previous pneumatic dilation was associated with long-term treatment failure (odds ratio, 3.41; 95% confidence interval, 1.25-9.23). Procedure-related adverse events occurred in 8.2% of patients and only 1 patient required surgical intervention. Abnormal esophageal acid exposure and reflux esophagitis were documented in 37.5% and 18% of patients, respectively. However, these rates are simply a reference number among a very selective group of patients. Conclusions POEM is safe and provides high initial clinical success and excellent long-term outcomes. Among patients with confirmed clinical response within 6 months, 6% had recurrent symptoms by 2 years.

Introduction There is wide variation in the treatment of early rectal cancers and complex rectal neoplasms. With increasing emphasis on minimally invasive techniques and organ preservation, we aimed to evaluate the utility of a standardised, structured and rational assessment of rectal tumours to inform decision making for patients referred to a tertiary unit specialising in early rectal cancer. Method Since 2012, our unit has employed a standard approach to the assessment of rectal lesions which includes multimodal endoscopic assessment of all lesions using white light, magnification chromoendoscopy and colonoscopic high frequency miniprobe ultrasound to inform treatment decisions. Patients can then be allowed a fully informed decision regarding treatment options, which include advanced endoscopic resection, minimally invasive transanal endoscopic microsurgery (TEMS) or laparoscopic segmental oncological resection, all of which are offered by our unit. Results 191 patients (mean age 71 years) with rectal tumours were referred to our unit for an assessment regarding suitability for local resection. Multimodal endoscopic evaluation assessed 128 lesions as benign and 63 as malignant. 125 lesions with a mean size of 70.9 mm were treated with endoscopic resection: 108 adenomas, 9 adenocarcinomas and 5 neurendocrine tumours. 92% were performed without general anaesthesia and 78% as day cases. There were 2 small perforations treated endoscopically with clips with no adverse sequelae. The recurrence rate was 10%, all managed endoscopically. At last surveillance 97% of patients were free from recurrence. None required a major resection. 37 patients underwent TEMS as curative treatment or for patients unfit for, or refusing major resection. Only 3 patients with benign neoplasms had TEMS. The few remaining patients were either directed to major surgical resection, palliative options or declined treatment. Conclusion A standardised rational approach employing multimodal endoscopic evaluation for assessing complex rectal neoplasms results in high rates of safe, effective organ preserving treatment with almost no patients with benign disease subjected to a surgical procedure. Disclosure of Interest None Declared

177 Variables Associated With Clinical Failure After PerOral Endoscopic Myotomy (POEM): a Case Control Study Vivek Kumbhari*, Pietro Familiari, Niels C. Bjerregaard, Saowanee Ngamruengphong, Mathieu Pioche, Bu Hayee, Nicholas Eleftheriadis, Weon-Jin Ko, Francois Mion, Sabine Roman, Alan H. Tieu, Mohamad H. El Zein, Joo Young Cho, Amyn Haji, Thierry Ponchon, Rastislav Kunda, Guido Costamagna, Mouen Khashab Division of Gastroenterology and Hepatology, Johns Hopkins Hospital, Baltimore, MD; Gastroenterologie, Gemelli University Hospital, Rome, Italy; Gastroenterology, Aarhus university hospital, Aarhus, Denmark; gastroenterology, Pavillon H Hopital Edouard Herriot, Lyon, France; gastroenterology, kings hospital, London, United Kingdom; Showa University Northern Yokohama Hospital, Yokohama, Japan; Gastroenterology, Soonchunhyang University Hospital, Bucheon, Korea (the Democratic People’s Republic of); Gastroenterology, Lyon university, Lyon, France; Gastroenterology, Digestive Endoscpy Unit Universita Cattolica del Sacro Cuore, Rome, Italy Background: Peroral endoscopic myotomy (POEM) aims to palliate symptoms of achalasia by reducing pressure at the lower esophageal sphincter (LES). However, the currently accepted determinant of outcomes for POEM is the symptom based Eckardt score. Current data demonstrates short-term clinical response in 82% to 100% of patients. Despite more than 7000 procedures performed worldwide, it is unclear what patient and procedural factors are associated with clinical failures after POEM. Determining such factors may facilitate better patient selection and optimize procedural techniques to improve procedural outcomes. Aims: To evaluate 1) pre and intra-procedural variables associated with and 2) physiologic characteristics of the LES, in patients with clinical failure post POEM. Method: Consecutive patients undergoing POEM at 7 tertiary centers (1 US, 5 European. 1 Asian) were included. Patients were excluded if their clinical follow up was less than 3 months. Relevant data was abstracted from a retrospective review of a multicenter prospectively acquired database. Patients were divided into 2 groups:1) those with a post POEM Eckardt score O3(Cases) and 2) those with a post POEM Eckardt score!3(Controls). Multivariate to identify factors associated with clinical failure was performed. Results: A total of 243 patients (mean age 49yr, female 52%) were included. The median pre-procedure Eckardt score was 8. A total of 18 (7.4%) patients had a post procedure Eckardt score of O3 (Cases) with the remaining 225 (92.6%) with serving as Controls. There were 44% of clinical failures with normalization of LES pressures (4s-IRP!15mmHg). On univariate analysis, there was no significant difference between the groups with regards to pre procedural characteristics including: age, sex, race, BMI, achalasia subtype and HREM. A sigmoid esophagus (OR 5.7, 95% CI 1.324.4, pZ0.03), prior Heller myotomy (OR 5.0, 95% CI 1.5-17.8, pZ0.01) and a higher mean baseline Eckardt score (OR 1.4, 95% CI 1.1-1.9, pZ0.01) were found to be significant risk factors for clinical failure. There was no significant difference in the groups with regards to intraprocedural characteristics including: length gastric myotomy, length of esophageal myotomy, orientation of myotomy (anterior vs. posterior) and thickness (full vs. inner circular) of myotomy. Multivariate analysis demonstrated a higher mean baseline Eckardt score was associated with risk of failure. Conclusions: In this large international multicenter study, clinical failures occurred in 7.4%. Sigmoid esophagus, prior Heller myotomy and higher mean baseline Eckardt score were associated with clinical failure. No intraprocedural factors were associated with clinical failure post POEM. Nearly half of clinical failures are unlikely to benefit from further therapy targeted at the LES and management of such patients is a clinical challenge. 178 Safety and Effectiveness of Per-Oral Endoscopic Myotomy (POEM) for Elderly Patients With Achalasia: a Comparison of Results for Older and Younger Patients Kanefumi Yamashita, Hironari Shiwaku*, Toshihiro Ohmiya, Richiko Beppu, Shinsuke Takeno, Takamitsu Sasaki, Satoshi Nimura, Haruhiro Inoue, Yuichi Yamashita Gastroenterological Surgery, Fukuoka University Faculty of Medicine, Fukuoka, Japan; Pathology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan; Digestive Disease Center, Showa University KotoToyosu Hospital, Tokyo, Japan Objective: The proportion of elderly persons in Japan is 25%, a rate that has been increasing every year. Therefore, it is of considerable clinical importance to review treatment plans for elderly patients with achalasia. The objective of this study is to evaluate the safety and effectiveness of POEM for elderly patients by comparing results from older and younger patients. Methods: A retrospective review was performed for 80 consecutive patients with achalasia who underwent POEM in our institution between September 2011 and May 2014. The patients were classified into two group: (A) those older and (B) those younger than 65 years. Age, previous treatment for achalasia, preoperative comorbidities, duration of symptoms, preand post-POEM Eckardt score, manometry findings, and treatment outcomes, including www.giejournal.org Vol duration of hospitalization and occurrence of complications, were compared between groups using chi-square and Student t-tests. Result: There were 19 patients in group A and 61 in group B. The median age was 76.1 7.1 years (range, 65-91 years) for group A and 39.9 12.4 years (range, 9-62 years) for group B. Group A had significantly more preoperative comorbidities than group B (47.4% vs. 13.1%; p Z 0.003). The mean duration of symptoms was significantly longer for group A than for group B (139.7 months [range, 1-396 months] vs. 89.3 months [range, 7-552 months]; p Z 0.001. The length of myotomy was statistically different between groups (10.3 cm [range, 5-26] in group A and 13.6 cm [range, 6-25] in group B; p Z 0.043). There were no statistical group differences for previous treatment for achalasia, median operation time, mean hospitalization, or occurrence of complications. Significant Eckardt score and integrated relaxation pressure reductions were achieved in both groups. No perioperative mortality or major postoperative complications occurred. Conclusions: POEM is a safe and effective operation for both older and younger patients. Although the elderly patients in our study had preoperative comorbidities, they achieved similar results to the younger patients, with similar rates of perioperative complications. Long-term follow-up studies are desirable to determine whether POEM may become an appropriate therapy for elderly patients with achalasia in the near future. 179 PerOral Endoscopic Short Versus Long Myotomy for the Treatment of Achalasia: a Case-Control Study Xiaowei Tang, Zhiliang Deng, Wei Gong*, Bo Jiang Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China Background: Peroral esophageal myotomy (POEM) is a novel endoscopic treatment for esophageal achalasia. It has gained popularity worldwide among surgeons and endoscopists, but no studies have compared peroral endoscopic short with long myotomy for achalasia. Aim: To compare clinical efficacy and safety between peroral endoscopic short and long myotomy. Methods: Between December 2011 and August 2013, 21 patients underwent peroral endoscopic short myotomy (myotomy length %7cm) in our department. These patients were 1:1 by age, gender, symptoms duration, Eckardt score, Chicago classification of achalasia, and LES pressure with 56 patients who underwent long myotomy (myotomy length O7cm). Procedure-related parameters, symptom relief and adverse events, manometry outcomes were compared between two groups. Results: A total of 77 patients, with a mean age of 54 19 years, underwent POEM. There was no significant differences in the age, sex and other baseline characteristics between the two groups. Mean myotomy length was 6.0 0.6 cm in short myotomy group, and 11.63 3.4 cm in long myotomy group (pZ0.01). The mean operation time was significantly shorter in shorter myotomy group than long myotomy group (49.2 19.2 min vs, 64.9 24.4 min , pZ0.01). During 6 months follow-up, treatment success (Eckardt score % 3) was achieved in 96.0% (20 of 21) of patients in short myotomy group and 95.0% (53 of 56) of patients in long myotomy group (pZ0.75). There was no significant differences in preand post-treatment D-value of symptom scores and lower esophageal sphincter pressures between groups (both pO0.05). There was also no statistical difference in the incidence of intraoperative complications (9.5% vs 8.9%, pZ0.18) and gastroesophageal reflux rate (10.7% vs 9.4%, pZ0.38) between the two groups. Conclusion: Peroral endoscopic short myotomy is comparable with long myotomy for treating achalasia with regard to short-term clinical efficacy and safety, and have the advantage of shorter procedure time. Table 1. Clinical outcomes of POEM procedure ume 81, No. 5S : 2015 Long myotomy

Introduction Two-thirds of patients with reflux symptoms will have a normal white light endoscopy (WLE). Using high definition narrow-band imaging (NBI), however, we found abnormalities in the distal oesophagus correlating with histologic findings of reflux. A common appearance was noted in patients referred for investigation of reflux (where endoscopy was otherwise normal). This was termed the ‘linear furrow’ sign (LFS) as it comprised of linear, alternating lighter and darker ‘ridges’ of mucosa resembling furrows in a ploughed field. This observational cohort study was conducted prospectively to establish the relevance of the LFS. Method Consecutive patients referred for investigation of reflux underwent endoscopy (BH or AH) to the institution protocol: a pair of routine, non-targetted distal and mid-esophageal biopsies were taken to examine for microscopic changes of reflux and to exclude eosinophilic esophagitis (EoE). Prior to biopsies, the oesophagus was examined using NBI. The endoscopist’s opinion as to whether the LFS was present was recorded in the routine report and digital still images captured. Histology was reported in the routine clinical service, then reviewed by a single experienced Histopathologist (HAA), blinded to endoscopic findings. Positive biopsies were those initially reported as “findings compatible with reflux”, but in each case the reviewing Histopathologist recorded the changes contributing to this overall impression. Sensitivity and specificity of the LFS was calculated using biopsies as the gold standard. Results n = 31 with normal WLE were examined (13F; mean age 44.3 ± 15.0 yrs). The LFS was present (LFS+) in 25 patients, extending approximately 4–5 cm above the squamocolumnar junction. Histologic examination of biopsies from this region demonstrated changes consistent with reflux in 23/25. 6 patients were LFS-, with normal histology in 5. Mid-esophageal biopsies were positive in only three patients. In one, diagnostic criteria for EoE were met (responding completely to acid suppression). Magnification endoscopy with NBI demonstrated that the changes seen arise from the impression of a ridged appearance to the mucosal surface – most likely reflecting elongation of papillae and basal cell hyperplasia. Spongiosis (dilated intercellular spaces; DIS) was demonstrable in 75% of LFS+. Although reflux symptoms were not systematically evaluated, a self-reported response to PPI was noted in 70% of such patients (LFS+, DIS+) and only 10% of those without (LFS-, DIS-; p Conclusion The LFS was detected in 80% of patients, achieving diagnostic accuracy of 90% and appears to relate to self-reported symptomatic response to PPI. A further prospective study is under way to determine the clinical significance of this finding. Disclosure of interest None Declared.