Gideon Lipman

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.

Comparing outcome of radiofrequency ablation in Barrett’s with high grade dysplasia and intramucosal carcinoma: a prospective multicenter UK registry

BACKGROUND AND STUDY AIM Mucosal neoplasia arising in Barretts esophagus can be successfully treated with endoscopic mucosal resection (EMR) followed by radiofrequency ablation (RFA). The aim of the study was to compare clinical outcomes of patients with high grade dysplasia (HGD) or intramucosal cancer (IMC) at baseline from the United Kingdom RFA registry. PATIENTS AND METHODS Prior to RFA, visible lesions and nodularity were removed entirely by EMR. Thereafter, patients underwent RFA every 3 months until all visible Barretts mucosa was ablated or cancer developed (end points). Biopsies were taken at 12 months or when end points were reached. RESULTS A total of 515 patients, 384 with HGD and 131 with IMC, completed treatment. Prior to RFA, EMR was performed for visible lesions more frequently in the IMC cohort than in HGD patients (77 % vs. 47 %; P < 0.0001). The 12-month complete response for dysplasia and intestinal metaplasia were almost identical in the two cohorts (HGD 88 % and 76 %, respectively; IMC 87 % and 75 %, respectively; P = 0.7). Progression to invasive cancer was not significantly different at 12 months (HGD 1.8 %, IMC 3.8 %; P = 0.19). A trend towards slightly worse medium-term durability may be emerging in IMC patients (P = 0.08). In IMC, EMR followed by RFA was definitely associated with superior durability compared with RFA alone (P = 0.01). CONCLUSION The Registry reports on endoscopic therapy for Barretts neoplasia, representing real-life outcomes. Patients with IMC were more likely to have visible lesions requiring initial EMR than those with HGD, and may carry a higher risk of cancer progression in the medium term. The data consolidate the approach to ensuring that these patients undergo thorough endoscopic work-up, including EMR prior to RFA when necessary.

AODTU-001 Radiofrequency ablation in patients with symptomatic anaemia secondary to gastric antral vascular ectasia

Introduction Gastric astral vascular ectasia (GAVE) is a rare cause of gastrointestinal bleeding (GIB). Patients often require regular blood transfusions and many require oral or intravenous iron to manage symptomatic anaemia. Endoscopic therapy includes argon plasma coagulation (APC), YAG laser therapy and band ligation. In some patients, these measures are unsuccessful and they remain transfusion dependent with significant effects on health and quality of life. Radio-frequency ablation (RFA) may provide a solution. Method Patients who had remained anaemic and/or transfusion or iron dependent were eligible. Other causes of GIB were excluded. Treatment with RFA was carried out with focal RFA at 12 J/cm2 with 3 applications to all visible areas of GAVE by a single endoscopist. Patients had up to 2 RFA treatments 6 weeks apart before entering the follow up phase. Data were collected before and after treatment. The primary outcome was change in haemoglobin (Hb) 3 months after treatment. Secondary outcomes were a reduction in frequency of blood transfusions and/or iron (PO or IV) in the 3 months before and after RFA treatment. Endoscopic surface area (SA) regression of areas of GAVE were analysed by asking 3 expert endoscopists to estimate the overall% change in SA following treatment by examining endoscopic images of the stomach before and after treatment. Results 16 patients have undergone RFA for refractory GAVE. The median age was 70 years (IQR 56–84). 13/16 (82%) were female. 12 were previously treated with APC, 3 with LASER and 2 of those treated with APC had also had band ligation. In the 3 months prior to treatment, 11/16 were on oral iron, 2/16 were on IV iron. 11/16 required blood transfusions. 8/16 required both iron and blood transfusions. The median number of RFA treatments was 1 (IQR 1–2). No patients had recorded complications of RFA. The mean pre-treatment Hb was 99.5 g/L (95% CI 90.3–108.6 g/L). The mean post treatment Hb at 3 months after treatment was 121 g/L (95% CI 112–129 g/L). The mean change in Hb was +20.5 g/L (95% CI 8.8–30.0 g/L) (p=0.0026). Post treatment, only 2/11 (18%) of the patients who required transfusion prior to the procedure had ongoing transfusions. Only 2/13 (15%) patients who were previously on iron had ongoing iron requirements. The mean surface area regression when scored by 3 upper GI endoscopists was 51.6%. [95% CI 38.7–64.4] Conclusion RFA for patients with symptomatic anaemia due to GAVE is a novel treatment therapy for a difficult cause of GI bleeding. This single centre experience suggests it can reduce transfusion dependence and iron supplementation in some patients with an improved Hb after treatment. The required number of treatments is small and it appears safe. Disclosure of Interest None Declared

Endoscopic management of Barrett's and early oesophageal neoplasia

Barretts oesophagus (BO) is the only known precursor to oesophageal adenocarcinoma (OAC). Dysplasia and intramucosal cancer arising in BO can safely be treated with endoscopic eradication therapy (EET) due to the low risk of subsequent lymph node metastasis. Treatment at an early stage is paramount due to the ongoing poor prognosis and outcomes of patients with advanced OAC. The mainstay of treatment is endoscopic resection of visible lesions for accurate staging followed by ablation therapy to all remaining columnar-lined epithelium, most commonly with radiofrequency ablation. Successful eradication of dysplasia can be achieved in >95% of patients with this EET combined approach.

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

PWE-078 Magnification Endoscopy with I-Scan Imaging and Acetic Acid Chromoendoscopy in Barrett’s Oesophagus Improves Neoplasia Detection

Introduction Barrett’s oesophagus (BE) is the pre-cursor for oesophageal adenocarcinoma. Endoscopic surveillance is performed in BE patients to detect dysplasia as an early treatment target. Current surveillance relies on random quadrantic biopsies every 1–2 cm through the BE with targeted biopsies for areas of suspicion. This strategy samples less than 5% of the BE mucosa. We present a novel endoscopic classification system utilising magnification chromo-endoscopy with i-Scan (PENTAX HOYA, Japan) image enhancement technology and acetic acid to improve dysplasia recognition in BE. Methods High definition (HD) video recordings of suspicious lesions were collected from patients with non-dysplastic (ND-BE) and dysplastic (D-BE) BE undergoing endoscopy at a high volume tertiary centre. Lesions were recorded with magnification endoscopy in all i-Scan modes both before and after application of 2% acetic acid (ACA) before sampling with biopsy forceps or endoscopic mucosal resection to confirm the histological diagnosis. Six expert endoscopists scored videos using a previously validated mucosal (M) and vascular (V) classification system. Normal mucosa was defined as regular circular or villous pits (M1) and abnormal mucosa defined as distorted or irregular pits or featureless mucosa (M2). Normal vascular pattern was defined as regular and uniform vessels (V1) and abnormal vascular pattern was defined as irregular, dilated corkscrew vessels (V2). Dysplasia was classified if the lesion was felt to be either M2 or V2. Results 63 lesions (36 D-BE, 27 ND-BE) were recorded (30 before ACA and 33 after ACA) for analysis. Experts’ average accuracy for dysplasia prediction was 67.8% pre ACA and 75.9% after ACA (p = 0.01). ACA improved the sensitivity of our novel classification system for neoplasia detection from 81% to 88% (p = 0.04). Interobserver Kappa values were 0.253 pre ACA and 0.369 after ACA. Conclusion Experts can diagnose D-BE in up to three-quarters of cases using i-Scan magnification endoscopy with acetic acid. ACA improves the sensitivity of diagnosing D-BE. The novel classification system for BE neoplasia has fair agreement between expert endoscopists. Disclosure of Interest None Declared

PTH-129 Machine Learning Creates A Simple Endoscopic Classification System that Improves Dysplasia Detection in Barrett’s Oesophagus in Non-Expert Endoscopists

Introduction Barrett’s Oesophagus (BE) is the pre-cursor to oesophageal adenocarcinoma. Endoscopic surveillance is performed to detect dysplasia in BE as it is likely to be treatable. Machine Learning (ML) is a technology that generates simple rules, known as a Decision Tree (DT). Using a DT generated from Expert Endoscopists (EE), we hypothesised that this could be used to improve dysplasia detection in Non-Expert Endoscopists (NEE). Methods Endoscopic videos of Non-Dysplastic (ND-BE) and Dysplastic (D-BE) BE were recorded. Areas of interest were biopsied. Videos were shown to 3 EE (blinded) who interpreted mucosal & vascular patterns, presence of nodularity/ulceration & suspected diagnosis. Acetic Acid (ACA) was sometimes used. EE answers were inputted into the WEKA package to identify the most important attributes and generate a DT to predict dysplasia. NEE (GI registrars and medical students) scored these videos online before & after online training using the DT (Fig 1). Outcomes were calculated before & after training. Student’s t-test was used (p < 0.05). Results Videos from 40 patients (11 pre/post ACA) were collected (23 ND-BE, 17 D-BE). EE mean accuracy of dysplasia prediction was 96% using the DT. Mean sensitivity/specificty were 93%/99%. Neither vascular pattern nor ACA improved dysplasia detection. Students had a high sensitivity but poor specificity as they ‘overcalled’ normal areas. GI registrars did the opposite. Training significantly improved sensitivity of dysplasia detection amongst registrars without loss of specificity. (Table 1). Specificity rose in students without loss of sensitivity and significant improvement in overall detection.Abstract PTH-129 Table 1 Accuracy, sensitivity and specificity amongst both groups of non-experts before and after training Registrars, n = 13 Students, n = 9 Both, n = 22 Accuracy, Before/After training (%), p-value 65/68, 0.07 53/63, 0.0005 60/66, 0.0005 Sensitivity, Before/After training (%), p-value 71/83, 0.00002 83/84, 0.044 76/83, 0.00079 Specificity, Before/After training (%), p-value 60/57, 0.2 31/49, 0.00008 48/54, 0.02Abstract PTH-129 Figure 1 Conclusion ML can generate a simple algorithm from EE to accurately predict dysplasia. Once taught to NEE, it yields a significantly higher rate of dysplasia detection. This opens the door to standardised training and assessment of competence in those performing endoscopy in BE. Disclosure of Interest None Declared

841 Residual Intestinal Metaplasia After Successful Endoscopic Therapy for Barrett's Related Neoplasia Confers Higher Long Term Risk for Disease Recurrence, on Behalf of the UK RFA Registry

Introduction Endoscopic resection (ER) followed by Radiofrequency ablation (RFA) is the first line treatment for neoplastic Barrett’s oesophagus (BE). Metachronous neoplasia after focal eradication of disease is ~20%. We examine data from the UK registry of 28 centres to establish if residual metaplastic BE carries a risk of disease recurrence. Methods Visible lesions were removed by EMR. Patients then underwent RFA 3 monthly. Biopsies were taken at 12 months to assess treatment success with repeat biopsies every 6–12 months thereafter. Dysplasia recurrence was compared in patients who had complete reversal of BE and neoplasia (CR-IM) to those in whom dysplasia alone was eradicated (CR-D only). Residual BE was confirmed with visible columnar epithelium proximal to the OGJ with biopsies showing IM. Results 517 patients achieved CR-IM & 96 patients achieved CR-D only after 12 months treatment . Sex & ER rates were not significantly different between groups. The CR-D only group were older (mean age 70 vs 67, p Conclusion Endotherapy should aim to clear neoplasia and underlying metaplastic BE to improve long term outcome. Patients with CR-D but not CR-IM at the end of treatment have an increased risk of neoplasia recurrence. This may have implications for post treatment surveillance intervals. Disclosure of Interest None Declared

Monitoring the premalignant potential of Barrett's oesophagus'

The landscape for patients with Barretts oesophagus (BE) has changed significantly in the last decade. Research and new guidelines have helped gastroenterologists to better identify those patients with BE who are particularly at risk of developing oesophageal adenocarcinoma. In parallel, developments in endoscopic image enhancement technology and optical biopsy techniques have improved our ability to detect high-risk lesions. Once these lesions have been identified, the improvements in minimally invasive endoscopic therapies has meant that these patients can potentially be cured of early cancer and high-risk dysplastic lesions without the need for surgery, which still has a significant morbidity and mortality. The importance of reaching an accurate diagnosis of BE remains of paramount importance. More work is needed, however. The vast majority of those undergoing surveillance for their BE do not progress towards cancer and thus undergo a regular invasive procedure, which may impact on their psychological and physical well-being while incurring significant cost to the health service. New work that explores cheaper endoscopic or non-invasive ways to identify the at-risk individual provides exciting avenues for research. In future, the diagnosis and monitoring of patients with BE could move away from hospitals and into primary care.

Reply to Kristo et al.

We thank you for your observations and comments about the role of surgical treatment for acid reflux in maintaining long-term disease remission after successful endoscopic therapy. We share your observations that although, in most patents, with combined endoscopic resection and radiofrequency ablation (RFA), we are able to clear the mucosal neoplasia and intestinal metaplasia that is Barrett’s esophagus, we do not reverse the persisting reflux insult that drives the biological transformation to Barrett’s esophagus and neoplasia. The ongoing requirement for acid suppression after successful endoscopic treatment may well reduce the quantity of acid exposure to the distal esophagus but this has little impact on the number of reflux events overall [1]. Toxic compounds within the refluxate that can lead to persistent damage to squamous mucosa include duodenogastric contents such as bile, pepsin, and pancreatic proteolytic enzymes [2]. Furthermore, the mechanical clearance of refluxate after endotherapy might also be impaired as has been shown in patients with mucosal esophagitis when compared to those with endoscopy-negative reflux disease [3], a concept yet to be explored in the context of refractory Barrett’s esophagus. Shaheen at al. [4] showed from data derived from the US registry that in patients undergoing endoscopic therapy for Barrett’s neoplasia prior antireflux surgery made no difference to the outcome. The authors examined 5537 patients undergoing RFA, of which 301 (5.4 %) had had a prior fundoplication. Complete eradication of intestinal metaplasia and dysplasia were achieved in 71 % and 87 %, respectively, of patients with a fundoplication, and 73 % and 87 %, respectively, of patients without a fundoplication (P = non-significant for both). Therefore the authors concluded that prior antireflux surgery made no difference to the outcome. However, there was little emphasis on the selection criteria for antireflux surgery or on the manometric and reflux characteristics that led to the surgical decision-making. The role of surgery after successful endoscopic treatment has yet to be examined and may well find a place in carefully selected patients in whom significant reflux is more likely after successful therapy – for example those with a large hiatus hernia and significant exposure to acid (or exposure to weak acid/non-acids such as bile) despite maximum medical therapy.