Charles Gordon

Consensus Statements for Management of Barrett's Dysplasia and Early-Stage Esophageal Adenocarcinoma, Based on a Delphi Process

BACKGROUND & AIMS Esophageal adenocarcinoma (EA) is increasingly common among patients with Barretts esophagus (BE). We aimed to provide consensus recommendations based on the medical literature that clinicians could use to manage patients with BE and low-grade dysplasia, high-grade dysplasia (HGD), or early-stage EA. METHODS We performed an international, multidisciplinary, systematic, evidence-based review of different management strategies for patients with BE and dysplasia or early-stage EA. We used a Delphi process to develop consensus statements. The results of literature searches were screened using a unique, interactive, Web-based data-sifting platform; we used 11,904 papers to inform the choice of statements selected. An a priori threshold of 80% agreement was used to establish consensus for each statement. RESULTS Eighty-one of the 91 statements achieved consensus despite generally low quality of evidence, including 8 clinical statements: (1) specimens from endoscopic resection are better than biopsies for staging lesions, (2) it is important to carefully map the size of the dysplastic areas, (3) patients that receive ablative or surgical therapy require endoscopic follow-up, (4) high-resolution endoscopy is necessary for accurate diagnosis, (5) endoscopic therapy for HGD is preferred to surveillance, (6) endoscopic therapy for HGD is preferred to surgery, (7) the combination of endoscopic resection and radiofrequency ablation is the most effective therapy, and (8) after endoscopic removal of lesions from patients with HGD, all areas of BE should be ablated. CONCLUSIONS We developed a data-sifting platform and used the Delphi process to create evidence-based consensus statements for the management of patients with BE and early-stage EA. This approach identified important clinical features of the diseases and areas for future studies.

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.

53 Six Year Disease Durability Outcomes on Patients Treated With Endoscopic Therapy for Barrett's Related Neoplasia From the UK Registry

Introduction Endoscopic therapy with combined Endoscopic mucosal resection (EMR) followed by Radiofrequency ablation (RFA) is now the recommended first line treatment for patients with Barrett’s (BE) related neoplasia confined to the oesophageal mucosa. Method We examine prospective data from the United Kingdom registry of patients undergoing RFA/EMR for BE neoplasia since 2008. Before RFA, visible lesions and nodularity were entirely removed by EMR. Thereafter patients underwent RFA 3 monthly until all visible BE was ablated or cancer developed (endpoints). Biopsies were taken at 12 months or when endpoints reached. Follow up endoscopies were performed periodically in all patients to check for recurrences thereafter. All patients who had completed at least 12 months of follow up after successful treatment were included in the analysis to examine durability of disease reversal long term. Results 282 patients (81% male, mean age 70 years) have completed the 12 month treatment protocol with a minimum of 12 months follow up thereafter. At median follow up of 37 months (IQR 29–49), 93% of patients with successful disease reversal were still free of neoplasia and 88% free of intestinal metaplasia recurrence. Cancer progression at this same time was seen in 1.4% of patients. Kaplan Meier (KM) statistics demonstrated a predicted 3 year neoplasia free survival in 88% of patients. At 5 and 6 years this was 86%. Similarly KM analysis showed that at 3 years 81% of patients would be free form BE and at 5 and 6 years this figure was 73%. Conclusion We report long term outcomes of a large cohort of patients with BE neoplasia who have had successful endoscopic therapy with RFA/EMR. This approach appears to have a lasting disease free benefit in the majority of patients. Recurrences do occur in a minority of patients and highlights the need for follow up in those fit for endoscopy. All collaborators of the UK RFA registry are acknowledged for their contributions to data collection for this work. Disclosure of interest None Declared.

Tu1097 HALO Radiofrequency Ablation for High Grade Dysplasia and Early Mucosal Neoplasia Arising in Barrett's Oesophagus: Interim Results Form the UK HALO Radiofrequency Ablation Registry

Introduction Barrett9s oesophagus (BE) is the pre-cursor to oesophageal adenocarcinmoa (OAC). High grade dysplasia (HGD) and early mucosal neoplasia in BE has historically been treated with surgery. Recently there is a shift towards minimally invasive endotherapy with endoscopic mucosal resection (EMR) and Radiofrequency ablation (RFA). Methods Prospective registry from 14 UK centers to audit RFA outcomes in patients with HGD and early neoplasia in BE. Prior to RFA, any visible lesions were first removed by EMR. Patients then underwent RFA 3 monthly until all visible BE was ablated or cancer developed. Biopsies were taken at the end of this protocol. Results 216 patients have completed protocol, mean age 68.6 years (40–90), 81% male. Mean time to protocol end 11.3 months (IQR 8–14.3), median 2 ablations and mean of 2.4 (2–6) during protocol with mean 1.4 circumferential ablations and 1.2 focal ablations performed during protocol. Mean length BE segment ablated is 5.8 cm (1–20). CR-HGD was achieved in 83% patients at protocol end biopsy. CR-D was 76% and CR-BE 50% at this point. CR-D was more likely in short segment BE ( Conclusion This is the largest series to date of patients undergoing RFA from 14 UK centers. End of protocol CR-D is satisfactory at 76% and successful eradication appears to be durable. Patients with short segment BE are likely to respond better. Our data represent real life outcomes of integrating minimally invasive endotherapy into demanding endoscopy service commitments. Competing interests 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

OC-054 Development and Validation of a Classification System to Identify Barrett’s Neoplasia Using Acetic Acid Chromoendoscopy: The Predict Classification

Introduction Neoplasia in Barrett’s can be discrete and patchy. Acetic acid chromoendoscopy (AAC) has been demonstrated to highlight neoplastic areas allowing for earlier treatment. Previous efforts to create a classification system for AAC have not been systematic and rigorous in their methodology. We aimed to develop and validate a classification system to identify Barrett’s neoplasia using AAC. Methods Three expert AAC endoscopists (PB, GLW, OP) formed a working group to identify AAC component criteria of non-dysplastic and dysplastic Barrett’s using a modified Delphi Method. Following this, a panel of 7 AAC experienced endoscopists assessed the performance of each individual criterion by reviewing a bespoke online database of 40 images and 40 videos of non-dysplastic and dysplastic Barrett’s lesions. Finally, we assessed the diagnostic reproducibility of the validated criteria by asking 13 non-AAC experienced endoscopists to complete an assessment tool of 40 images and 20 videos. Results The component criteria identified by the expert AAC endoscopists were as follows Early focal loss of acetowhitening Present: Indicates the presence of neoplasia Absent: Indicates the absence of neoplasia Surface pattern Normal (Large uniformly distributed pits): Indicates non-neoplastic Barrett’s Abnormal (Compact, irregular or absent pits): Indicates neoplastic Barrett’s A total of 560 observations were undertaken to validate these criteria. The sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) are shown in Table 1:Abstract OC-054 Table 1 Validation results of the classification criteria Criteria Sensitivity Specificity NPV PPV Loss of acetowhitening 96.2%(93.4–97.9%) 93.8%(88.9–96.9%) 90.9%(85.5–94.8%) 97.5%(95.4–98.8%) Surface pattern• Normal• Abnormal 77.0%(69.7–83.3%)99%(97.5–99.7%) 99.0%(97.5–99.7%)77.0%(69.7–83.3%) 91.4%(88.4–93.9%)96.9%(92.2–99.1%) 96.9%(92.2–99.1%)91.4%(88.4–93.9%) When the AAC validated criteria are applied by the 13 endoscopists, the sensitivity, specificity, NPV and PPV of detecting neoplastic Barrett’s are 98.5%, 64.0%, 97.5% and 72.5% respectively. Conclusion We have developed and established the validity of a simple classification system to identify Barrett’s neoplasia using AAC. When non-AAC experienced endoscopists apply these criteria, the sensitivity and NPV meet the recommended PIVI threshold. 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

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

PWE-176 Palliative stenting in oesophageal cancer

Introduction Palliative stenting is now established as a major treatment for dysphagia resulting from inoperable oesophageal cancer. There are many possible complications after oesophageal stent insertion; most of these present with increasing dysphagia; however pain, bleeding, and reflux are also common. Although data on rates of various complications are available, there are no agreed standards to audit performance against, nor any requirement to do so. As this is a palliative procedure, success in symptom control is paramount; if this is not being achieved, then the appropriateness of the procedure must be questioned. As with any invasive procedure, complication rates are affected by multiple variables: technique, type of stent, length and site of stricture, operator experience, and patient co-morbidities. As a result of these variables, stated complication rates also vary: Only one study reported a rate of dysphagia (29%); migration occurred in 5–15% of cases, tumour overgrowth 5–20%, and food bolus obstruction in 5–15%. Quoted median survival ranged from 61–104 days, with a 30-day mortality of 20–28%. Method A retrospective study of all patients undergoing oesophageal stent insertion at a single endoscopy unit during 2012–13 was undertaken, looking for evidence of complications, repeat interventions, and for survival statistics after stent insertion. Patients who had undergone stent insertion for reasons other than oesophageal malignancy were excluded. Results During the two-year period, 74 stents were inserted in 62 patients for palliation of malignant dysphagia. Of these stent insertions 24 (32.4%) were documented to have recurrent dysphagia, of which the causes were: tumour over- or ingrowth in 7 (9.5%); stent migration in 5 (6.8%); obstruction due to gastric folds, hiatus hernia, or anti-reflux valve in 3.(4.1%); and food bolus obstruction in 2 cases (2.7%). In total there were documented complications post stent in 32 (43.2%) of all stent insertions, with pain in 8 (10.8%), bleeding in 6 (8.1%), and nausea or refluxing 3 cases (4.1%) accounting for the complications which did not cause dysphagia. Median survival of the 74 patients after stent insertion was 95 days and 30-day mortality was 9.7% (6 patients). It is important to note that with retrospective data analysis, some data are not available, due to variations in recording at the time and a reliance on the patient to report symptoms to a clinician. Conclusion Palliative stenting at this centre continues to be an effective treatment for patients with malignant dysphagia. Outcomes compare favourably with published data in terms of recurrent dysphagia, other complications, and mortality. Steps to improve post-procedure monitoring in the form of a “stent registry” with prospective collection of data by telephone or face-to-face follow up could be useful in future service development. Disclosure of interest None Declared.