M Di Pietro

Improvement over time in outcomes for patients undergoing endoscopic therapy for Barrett's oesophagus-related neoplasia: 6-year experience from the first 500 patients treated in the UK patient registry

Background Barretts oesophagus (BE) is a pre-malignant condition leading to oesophageal adenocarcinoma (OAC). Treatment of neoplasia at an early stage is desirable. Combined endoscopic mucosal resection (EMR) followed by radiofrequency ablation (RFA) is an alternative to surgery for patients with BE-related neoplasia. Methods We examined prospective data from the UK registry of patients undergoing RFA/EMR for BE-related neoplasia from 2008 to 2013. Before RFA, visible lesions were removed by EMR. Thereafter, patients had RFA 3-monthly until all BE was ablated or cancer developed (endpoints). End of treatment biopsies were recommended at around 12 months from first RFA treatment or when endpoints were reached. Outcomes for clearance of dysplasia (CR-D) and BE (CR-IM) at end of treatment were assessed over two time periods (2008–2010 and 2011–2013). Durability of successful treatment and progression to OAC were also evaluated. Results 508 patients have completed treatment. CR-D and CR-IM improved significantly between the former and later time periods, from 77% and 56% to 92% and 83%, respectively (p<0.0001). EMR for visible lesions prior to RFA increased from 48% to 60% (p=0.013). Rescue EMR after RFA decreased from 13% to 2% (p<0.0001). Progression to OAC at 12 months is not significantly different (3.6% vs 2.1%, p=0.51). Conclusions Clinical outcomes for BE neoplasia have improved significantly over the past 6 years with improved lesion recognition and aggressive resection of visible lesions before RFA. Despite advances in technique, the rate of cancer progression remains 2–4% at 1 year in these high-risk patients. Trial registration number ISRCTN93069556.

Past, present and future of Barrett's oesophagus

Barretts oesophagus is a condition which predisposes towards development of oesophageal adenocarcinoma, a highly lethal tumour which has been increasing in incidence in the Western world over the past three decades. There have been tremendous advances in the field of Barretts oesophagus, not only in diagnostic modalities, but also in therapeutic strategies available to treat this premalignant disease. In this review, we discuss the past, present and future of Barretts oesophagus. We describe the historical and new evolving diagnostic criteria of Barretts oesophagus, while also comparing and contrasting the British Society of Gastroenterology guidelines, American College of Gastroenterology guidelines and International Benign Barretts and CAncer Taskforce (BOBCAT) for Barretts oesophagus. Advances in endoscopic modalities such as confocal and volumetric laser endomicroscopy, and a non-endoscopic sampling device, the Cytosponge, are described which could aid in identification of Barretts oesophagus. With regards to therapy we review the evidence for the utility of endoscopic mucosal resection and radiofrequency ablation when coupled with better characterization of dysplasia. These endoscopic advances have transformed the management of Barretts oesophagus from a primarily surgical disease into an endoscopically managed condition.

PTU-178 Clinical Utility Of Endofaster® In Patients On Chronic Ppi Therapy Undergoing Upper Gi Endoscopy

Introduction Patients undergoing upper GI endoscopy (OGD) are often on chronic PPI therapy for dyspeptic symptoms or gastro-oesophageal reflux disease (GORD). Continued PPI therapy at the time of the endoscopy can influence the outcome of H. pylori testing via rapid urease test (CLO) or even histology. In addition, complete response to PPI in patient with GORD and/or Barrett’s oesophagus (BO) is often not fully predicted by the clinical history. We hypothesised that rapid testing of H. pylori status and gastric pH by Endofaster® could provide the physician with real-time information useful to influence patient management. Methods This pilot feasibility study included 135 consecutive patients at a single centre who underwent OGD for BO surveillance/endotherapy (n = 95), screening for hereditary diffuse gastric cancer (n = 11) and evaluation of GORD/dyspepsia (n = 29). The pH and the H.pylori status were measured on 4 mL of gastric aspirate using the Endofaster®, which connects to the suction port of the gastroscope. If clinically indicated, CLO test or gastric biopsies were performed. Endofaster® results were matched with the history of PPI intake (PPI type and time of last dose) and results of CLO and gastric histology. Results Overall, 109 patients were on chronic PPI treatment and of these 74% presented with gastric hypochloridia (pH >4) at Endofaster® analysis. Forty-nine patients reported PPI intake on the same day of the OGD and 15% of these (n = 7) had acid gastric pH (<4). Fifty-nine patients had CLO test and 57 had gastric histology results available, while 26 patients had both. Only 1 patient was positive for H. pylori on histology, which was also positive at Endofaster®. Two patients had a positive CLO test, of which one was Endofaster® positive for H. pylori. Eleven patients were positive at the Endofaster® but not at CLO, of which 91% were on chronic PPI (n = 10). Conclusion This feasibility study shows that a significant proportion of patients on chronic PPI therapy still have acidic gastric pH suggesting sub-optimal response to PPI. Endofaster® may detect H.pylori infection in patients on chronic PPI therapy, which are often false negatives when tested by CLO and histology. A prospective study matching Endofaster® data with gold standard tests for H. pylori status and gastro-esophageal reflux are needed to conclude on the clinical implications of these findings. Disclosure of Interest None Declared.

OC-029 Radiofrequency Ablation (Rfa) Confers Sustained Benefit for Squamous High Grade Dysplasia (Hgd) and Early Squamous Cell Carcinoma (Scc) in Patients who do not Progress following First Treatment

Introduction Oesphageal SCC carries a poor prognosis. Squamous HGD is the precursor lesion to SCC. Risk of progression to SCC with HGD can be 65% at 5 years. RFA is a minimally invasive technique with proven efficacy for early neoplasia arising in Barrett’s oesophagus. We present prospective data from 10 centres in the United Kingdom (UK) HALO registry. Methods Superficial lesions were removed by endoscopic mucosal resection (EMR) before RFA. Treatment consisted of a single ablation at 12J/cm2. Patients were followed up 3 months after treatment with biopsies. Those with residual dysplasia underwent further RFA until 12 months when they were assessed for treatment success or failure. Recurrent dysplasia was retreated with EMR/RFA. Primary outcomes were reversal of dysplasia (CR-D) at 12 months. Results 26 patients had RFA. Mean length mucosa ablated was 5.3 cm (1–14). 7/26 (27%) had EMR before RFA. Prior EMR did not confer benefit to outcome, nor did baseline disease length. Following first RFA, 6/26 patients (23%) progressed to invasive disease. Only one more patient progressed later in treatment course. CR-D was achieved in 50% at protocol end, mean 1.7 RFA treatments (1–4). 10/13 (77%) with successful RFA at 12 months remain disease free at most recent follow up (median 21 months). Kaplan Meier statistics show 2 years post treatment 68% patients are likely to remain in remission from dysplasia for those with successful outcome at 12 months. 5 patients (19%) required dilatations for oesophageal stricturing. Conclusion Squamous HGD & CIS are aggressive pathologies as evidenced by the fact that 23% patients in our cohort progressed to invasive disease despite RFA. However the majority who do not progress early (13/19 patients) achieve benefit & are more likely to have a successful & durable outcome. There is limited experience in the UK with RFA in these patients. Pre RFA EMR for visible lesions is limited in our series. As a result some patients may be under staged prior to RFA which may account for the high rate of progression after first treatment. Disclosure of Interest None Declared

PWE-106 Comparative analysis of efficacy and safety of standard and simplified radiofrequency ablation protocols for dysplastic barrett’s oesophagus: a retrospective study

Introduction The standard protocol for radiofrequency ablation (RFA) of Barrett’s oesophagus (BO) entails two treatment phases separated by cleaning of mucosal slough. A simplified protocol without the cleaning phase allows reduction of the procedure duration and number of intubations. The simplified protocol was proven to be non-inferior to the standard protocols in single application studies, but there is lack of data relative to the overall treatment pathway. The aim of this study was to compare overall safety and efficacy of the two protocols in two cohorts of patients treated with standard or simplified protocols. Method We collected data on 143 patients receiving RFA for dysplastic BO between December 2007 and October 2016 at a single institution. Until November 2012 all patients received the standard RFA protocol, which was thereafter substituted with the simplified one. In the standard protocol circumferential RFA consisted of two hits at 12 J/cm2 separated by cleaning phase and focal RFA consisted of double hit 15 J/cm2, cleaning and double hit at 15 J/cm2. In the simplified protocol circumferential RFA consisted of double hit at 12 J/cm2 without cleaning, while focal RFA consisted of triple hit at 12 J/cm2 without cleaning. Patients treated with a mixture of the two protocols were excluded. Outcomes included complete remission of dysplasia (CR-D), complete remission of intestinal metaplasia (CR-IM) and complication rate. Patient still receiving treatment after 18 months from the first RFA were regarded as failure. Results After exclusion of patient still on active treatment and those who received RFA with a mixture of the two protocols, 46 patients were included in the standard protocol and 50 patients in the simplified one. There was no difference between the two groups in terms of sex, length of the BO and size of the hiatus hernia. Patients in the standard group were significantly older (72.2 vs 67.4, p=0.02) and had significantly higher proportion of intramucosal cancer and lower proportion of low-grade dysplasia (LGD) (p=0.001) due to recent approval of RFA for LGD. The rates of CR-D and CR-IM with the standard protocol were 91% and 82%, respectively, and with the simplified protocol 100% and 88%, respectively, which was not significantly different. Stricture rate was significantly higher in the simplified group (9/50 vs 1/46, p=0.016), with a median number of dilations of 1 in each group. Conclusion In this cohort study assessing overall outcomes, the standard and simplified protocol were equally effective, but the simplified carried a higher risk of stricture, which could be easily managed endoscopically with a single dilatation in most cases. Disclosure of Interest None Declared

PWE-076 Specialist Centre Patient Volume Does Not Impact on Endoscopic Outcomes for Treatment of Barrett’s Dysplasia. Results from The UK Registry

Introduction Endoscopic mucosal resection (EMR) followed by Radiofrequency ablation (RFA) is first line treatment for mucosal Barrett’s oesophagus (BE) related neoplasia. The UK Registry collects data from patients at 28 sites undergoing RFA/EMR. We examine differences in outcomes between sites by patient volume. Methods All visible lesions were entirely removed by EMR. Patients then underwent RFA every 3 months until all visible BE was ablated. Biopsies were taken at 12 months to assess treatment success with repeat biopsies every 6–12 months thereafter. Centres were grouped by total numbers treated; low <50, medium 50–100 & high >100 patients. Only outcomes of those who had completed treatment were analysed. Results 675 patients completed treatment at 24 centres (median follow up 26 months), 414 at high volume (n = 5), 143 at medium volume (n = 4) & 118 at low volume centres (n = 15). There was no difference in entry criteria or demographics between groups. CR-D & CR-IM at 12 months are no different between the groups (CR-D 86–90%, CR-IM 74–81%). IM recurrence is significantly lower in high volume centres (16.1% vs 20.3% and 19.2%, Log Rank p < 0.001) but dysplasia recurrence is no different (Log Rank p = 0.12). Rescue EMR was performed less frequently in medium volume centres (0% vs high 5.3% and low volume 10%, p = 001). Conclusion Endotherapy for Barrett’s dysplasia is highly effective whatever the centre volume. The rescue EMR rate in medium volume centres is unexplained. Despite lower IM recurrence in high volume centres, dysplasia recurrence rates are not significantly different. Caseload volume of a centre in the UK Registry does not appear to affect outcome. Disclosure of Interest None Declared

OC-053 Lectin-Based Near infra-red Molecular Imaging for Dysplasia Detection in Barrett’s Oesophagus: An ex-vivo Study on Human Tissue

Introduction Detection of early neoplasia in Barrett’s oesophagus (BO) by white-light endoscopy is challenging due to the inconspicuous nature of dysplasia. Molecular imaging using fluorescently labelled wheat-germ agglutinin (WGA) is a promising tool as this topically applied imaging agent shows lower binding to dysplastic versus non-dysplastic BO.1 However in an endoscopy setting, the detection of fluorescence in the blue/green range is limited by high-levels of tissue autofluorescence. This limitation can be overcome by using near infra-red (NIR) imaging. We aimed to assess in an ex-vivo model the feasibility of WGA-based NIR imaging for detection of dysplasia in BO. Methods we recruited patients with early BO-related neoplasia undergoing endoscopic mucosal resection (EMR). Freshly collected EMR specimens were sprayed with WGA-IR800CW and then imaged with a high-sensitivity NIR camera. Fluorescence images were captured and up to two punch biopsies were collected from each EMR under fluorescence guidance. The EMRs were paraffin embedded, cut every 2 mm and processed for histopathological assessment. Each section was scored by an expert GI pathologist every 1 mm to construct a pathology grid, which was manually co-registered with the fluorescence image. The mean fluorescence intensity (MFI) of cells in dysplastic and non-dysplastic areas was compared by the Wilcoxon matched-pairs signed rank test. Only EMR specimens with at least one dysplastic gland were included in the analysis. In addition, the MFI of punch biopsies taken from dysplastic and non-dysplastic areas was also compared by Mann-Whitney test. Results Ten patients were recruited at a single centre. A total of 18 EMR specimens and 33 punch biopsies were collected, of which 10 were dysplastic. In the whole EMR analysis, we found a significantly lower MFI for dysplastic versus non-dysplastic areas (P = 0.0012), in accordance with the reported reduced binding of WGA to neoplastic BO epithelium. Similarly, we found a nearly 2 fold reduction in the MFI of punch biopsies taken from dysplastic as compared to non-dysplastic (ND) areas (P = 0.0002) (Figure 1).Abstract OC-053 Figure 1 Conclusion WGA-based NIR imaging is an effective method for differentiating dysplastic from non-dysplastic BO mucosa ex vivo, which reduces the effects of tissue autofluorescence. In-vivo studies are now required to test the efficacy of this method for detecting dysplasia during endoscopic surveillance. Reference 1 Bird-Lieberman, et al. Nat Med 2012. Disclosure of Interest None Declared

OC-040 First in-vivo study on the use of lectin-based molecular imaging in barrett’s oesophagus

Introduction The current standard for Barrett’s oesophagus (BO) endoscopic surveillance is based on random quadrantic biopsies every 2 cm. This is limited by sampling error due to inconspicuous dysplasia. We have previously found that an edible lectin (wheat germ agglutinin or WGA) has lower affinity for dysplastic compared to non-dysplastic BO and in an ex vivomodel of molecular imaging we showed that WGA-fluorescein in combination with autofluorescence imaging (AFI) can target dysplasia in BO (Bird-Lieberman, Nat Med, 2012). In this study we used a pre-operative setting to investigate in vivoWGA-based molecular imaging Method Inclusion criteria were: i. MDT referral to oesophagectomy for oesophageal adenocarcinoma (OAC) and ii.evidence of endoscopically visible BO associated to OAC on index endoscopy or staging endoscopic ultrasound. In the operating theatre prior to oesophagectomy, the oesophagus was first inspected by white light imaging to locate the tumour and measure the size of the associated BO. Imaging was then switched to AFI to locate AFI positive areas (red-purple colour). Up to two AFI negative areas (green colour) were also selected for control biopsy sampling. 20–30 mL of 5 µg/mL WGA-fluorescein were then sprayed onto the mucosal surface. After 5 min, the mucosa was gently washed with water and the oesophagus was inspected again in AFI mode. On WGA-enhanced AFI, areas of high WGA binding were located (WGA positive, green colour), as well as areas of low binding (WGA negative, red-purple and hence high risk). Targeted biopsies were taken for histopathological correlation. Histological outcome was binarised based on the presence or absence of dysplasia. Chi-squared test was used to compare diagnostic accuracy for dysplasia of AFI alone and WGA-enhanced AFI Results 16 patients were recruited at a single centre, of which 12 completed the protocol. 4 patients were excluded due to absence of visible BO associated with the OAC at the time of resection. Across the 12 patients a total of 41 endoscopic locations were selected for biopsy of which 29 were WGA negative and 12 were WGA positive. The overall sensitivity for dysplasia of AFI alone was 78% and the specificity was 50%. When compared to AFI alone, WGA improved sensitivity from 78% to 88%, with a slight increase in the specificity to 56%. AFI and WGA-enhanced AFI had an equal false positive rate (24%). No toxicity events where recorded. Conclusion WGA-based molecular imaging is safe and feasible in vivo. The use of WGA may improve the sensitivity of AFI for dysplasia, but larger studies in a surveillance population are required Disclosure of interest None Declared.

PTH-184 Superior patient preference and high diagnostic accuracy for the detection of barrett’s oesophagus using a novel, portable, probe-based transnasal endoscope

Introduction Barrett’s Oesophagus (BO) is the only recognised precursor to oesophageal adenocarcinoma. The second generation EG Scan™ system is portable with a disposable, ultrathin, probe-based imaging capsule; therefore it may be used in the community setting closer to the patient’s home. We aimed to compare the performance of unsedated transnasal endoscopy (TNE) using the EG Scan™ with conventional oesophagogastroduodenoscopy (C-OGD) for the detection of BO. Method This was a prospective, two-centre, diagnostic study with tandem design. Consecutive adult patients with histologically confirmed BO and those referred for assessment of reflux or dyspepsia were invited to participate. We excluded patients with recurrent epistaxis; nasal obstruction; and disease of the nasal cavity. All subjects underwent unsedated TNE (index test) followed by C-OGD (reference standard) on the same day, by two different operators blinded to the findings of each other. The primary outcome measure was the diagnostic accuracy for BO. In addition, procedure preference; tolerability (10-point visual analogue scale (VAS), 0 = worst and 10 = best); and adverse events questionnaires were administered on day 0 and day 14 after the procedures. Results 100 patients agreed to participate out of 439 subjects who were invited (22.8%). The mean age was 59.5 years (+/-13.7) and 63% were males. Prevalence of BO was 50%. 89 patients (89%) completed both procedures (11% failed TNE due to the inability to intubate the nasopharynx). Sensitivity, specificity and area under the receiver operating characteristic of TNE for the diagnosis of BO were 0.96 (95%confidence interval (CI) 0.85–0.99), 0.91 (95% CI 0.78–0.97), and 0.93 (95% CI 0.88–0.99), respectively. Patients reported higher preference for TNE compared to C-OGD on both day 0 (73.0% vs. 18.0%%, p < 0.001) and day 14 (64.2% vs. 16.0%, p < 0.001). Preference for TNE remained significantly higher in patients who had C-OGD under sedation (57.1% vs. 31.4%, p < 0.001). Subjects also reported significantly better experience (mean VAS) with TNE compared to C-OGD on day 0 (7.5 vs. 5.6, p < 0.001) and day 14 (7.3 vs. 5.1, p < 0.001). Two patients (2.2%) experienced transient pre-syncopal episodes. No serious adverse events occurred. Conclusion TNE using the EG Scan™ device was highly accurate for the detection of BO. More importantly, a significant majority of patients preferred TNE over C-OGD regardless of sedation use. The low test uptake could be due to the requirement for patients to undergo 2 procedures on the same visit. The EG Scan™ could potentially provide a true community-based screening tool for BO and oesophageal adenocarcinoma. Disclosure of interest None Declared.

PTU-145 Prophylactic total gastrectomy for hereditory gastric cancer syndrome

Introduction 1–3% of gastric cancers arise from hereditary predisposition syndromes. E-cadherin gene (CDH1) mutations are the best characterised of these and confer a life-time risk of approximately 80% for patients developing diffuse gastric cancer. Currently, the only definitive treatment available is prophylactic total gastrectomy (PTG). We present our experience of open PTG, focusing on the early outcomes. Method Twenty four consecutive patients with CDH 1 mutation underwent PTG from 2005 to 2014 (median age 33, range 22–51). All patients had at least one gastroscopy with biopsies taken according to the Cambridge Protocol and were assessed by a multi-disciplinary team within a high-volume Cancer Centre. All patients had an open posterior vagal sparing total gastrectomy with stapled oesophagojejunal anastomosis and Roux-en-Y reconstruction by a single surgeon. Twenty three patients had a D0.5 -1 lymphadenectomy; one patient with suspected invasive tumour had a D2 resection. Nasogastric tubes and abdominal drains were not used. Patients were mobilised on the first postoperative day with epidural analgesia. Oral fluids were restarted on postop day 3 and diet on day 5. Results There were two postoperative complications (8%) but no deaths; One patient had a jejuno-jejuno anastomotic leak 10 days after surgery requiring revisional surgery but made a full recovery. Another patient had bleeding which was managed conservatively with transfusion. Two patients developed anastomotic strictures and were successfully treated with endoscopic balloon dilatation. Median follow-up to date is 5 years (range: 3 months to 9 years). Histology showed scattered microscopic foci of intramucosal signet ring carcinoma (pT1a) in 23/24 patients (96%); the median number of foci was 7 (range: 1–182). No invasive tumours were found, all nodes were negative for tumour and all longitudinal margins were clear. The median lymph node yield was 5.5 (range: 1–26) and median hospital stay was 8 days (range: 6–10). Conclusion Open PTG can be performed with acceptable mortality and morbidity. Our challenge for the future is to offer minimally invasive PTG without increasing the risks. Disclosure of interest None Declared.