Abhinav Gupta

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.

Radiofrequency ablation for early oesophageal squamous neoplasia: Outcomes form United Kingdom registry

AIM To report outcomes on patients undergoing radiofrequency ablation (RFA) for early oesophageal squamous neoplasia from a National Registry. METHODS A Prospective cohort study from 8 tertiary referral centres in the United Kingdom. Patients with squamous high grade dysplasia (HGD) and early squamous cell carcinoma (ESCC) confined to the mucosa were treated. Visible lesions were removed by endoscopic mucosal resection (EMR) before RFA. Following initial RFA treatment, patients were followed up 3 monthly. Residual flat dysplasia was treated with RFA until complete reversal dysplasia (CR-D) was achieved or progression to invasive Squamous cell cancer defined as infiltration into the submucosa layer or beyond. The main outcome measures were CR-D at 12 mo from start of treatment, long term durability, progression to cancer and adverse events. RESULTS Twenty patients with squamous HGD/ESCC completed treatment protocol. Five patients (25%) had EMR before starting RFA treatment. CR-D was 50% at 12 mo with a median of 1 RFA treatment, mean 1.5 (range 1-3). Two further patients achieved CR-D with repeat RFA after this time. Eighty per cent with CR-D remain dysplasia free at latest biopsy, with median follow up 24 mo (IQR 17-54). Six of 20 patients (30%) progressed to invasive cancer at 1 year. Four patients (20%) required endoscopic dilatations for symptomatic structuring after treatment. Two of these patients have required serial dilatations thereafter for symptomatic dysphagia with a median of 4 dilatations per patient. The other 2 patients required only a single dilatation to achieve an adequate symptomatic response. One patient developed cancer during follow up after end of treatment protocol. CONCLUSION The role of RFA in these patients remains unclear. In our series 50% patients responded at 12 mo. These figures are lower than limited published data.

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-014 Patients With Intramucosal Carcinoma Arising In Barrett’s Eosophagus Have Similar Outcomes To Those With High Grade Dysplasia: Data From The United Kingdom Registry

Introduction Mucosal neoplasia arising in Barrett’s oesophagus (BE) can be treated with combined radiofrequency ablation (RFA) and endoscopic mucosal resection (EMR). Once there is submucosal invasion the risk of lymph node metastases increases and surgery is favoured. High grade dysplasia (HGD) and intramucosal carcinoma (IMC) arising from the mucosal layer in BE are defined as separate entities in the revised Vienna classification (category 4.1 and 4.4 respectively). Methods We examine prospective data from United Kingdom (UK) registry of patients undergoing RFA/EMR for BE neoplasia over past 5 years to compare outcomes between HGD and IMC patient cohorts. Histological confirmation of HGD or IMC was required on two separate occasions by specialist histopathologists prior to treatment. Before RFA, visible lesions were removed by EMR. Thereafter patients underwent RFA 3 monthly following which biopsies were taken at 12 months for clearance of dysplasia (CR-D) and BE (CR-IM). Twelve month outcomes, frequency of EMR, cancer progression and long term durability in both groups were examined. Results To date 367 patients with HGD and 125 with IMC have been treated. There is no difference in age, sex, baseline BE length between the 2 groups. EMR prior to RFA is far more prevalent in IMC cohort than HGD patients (78 vs. 45%, P < 0.0001). Patients had an average of 2–3 RFA treatments over 12 months (range 1–6) in both cohorts. Rescue EMR after starting RFA for new lesions was similar in both groups (HGD 7%, IMC 6.5%). CR-D and CR-IM in the HGD cohort was 85 and 69% respectively at 12 months. This was not significantly different in the IMC cohort (86 and 71%, p = 0.7). Overall progression to invasive cancer was not significantly different in either cohort (HGD 4.1%, IMC 7.2%). Kaplan Meir survival statistics did not show any difference in long term durability of successful neoplasia treatment in both groups (p = 0.9, log rank test), median follow up 20 months. Conclusion We report one of the largest series of patients undergoing endoscopic therapy for IMC arising in BE. Patients with IMC are more likely to have visible lesions that require EMR prior to RFA than those with HGD. However, once all visible lesions are removed, there is no statistical difference in clinical outcomes between the cohorts. Minimally invasive endoscopic therapy with RFA/EMR is a safe and effective treatment in patients with IMC. All collaborators of the UK RFA registry are acknowledged for their contributions to this work Disclosure of Interest None Declared.

PTU-171 Recurrence After Successful Radiofrequency Ablation For Barrett’s Related Neoplasia Is More Likely In Males: Data From The United Kingdom Patient Registry

Introduction Barrett’s oesophagus (BE) can lead to oesophageal adenocarcinoma (OAC). BE is more prevalent in males. Endoscopic mucosal resection (EMR) for visible lesions followed by Radiofrequency ablation (RFA) have become first line treatment for patients with BE related neoplasia. Recurrence after treatment can occur in up to 25% of patients. Risk factors for recurrence are unclear. Methods We examine prospective data from United Kingdom (UK) registry of patients undergoing RFA/EMR over past 5 years. We examine if recurrence after treatment is influenced by gender, baseline histology, BE length and prior EMR. Before RFA, visible lesions were removed by EMR. Thereafter patients underwent RFA 3 monthly. Biopsies were taken at 12 months and outcomes for clearance of dysplasia (CR-D) and BE (CR-IM) were assessed. After successful treatment patients were followed up 3 monthly for the first year, 6 monthly for second year and annually thereafter. Biopsies were taken from 1cm below neo z-line and previously treated BE segment. Results A total of 412 males and 95 females have been treated with no statistical difference in baseline BE length, histology or prior EMR in both groups. CR-D in Males was 84% and CR-IM 80%. In females CR-D was 86% and CR-IM 64% and not significantly different (p = 0.61 and p = 0.22, respectively). Progression to cancer was 3% in both cohorts at 12 months. There were 21 patients from both groups with recurrent dysplasia on follow up biopsy after successful treatment. Median time to recurrence in these after successful RFA was 380 days (IQR 177–615). Twenty recurrences were in males compared to one in female group which was statistically significant (p = 0.04). There were 11 recurrences of IM alone in patients who had confirmed CR-IM at 12 months. All were in male patients (median time to recurrence of 626 days, IQR 237–822). Baseline BE length, histology, prior EMR did not influence risk of recurrence of dysplasia or IM. Conclusion RFA for BE related neoplasia is equally effective in both males and females. Recurrence of neoplasia after successful eradication although uncommon overall is more common in males. The much lower recurrence rate in women raises the possibility that they could be discharged from follow up after successful treatment or have prolonged surveillance intervals compared to men. This could reduce the burden of surveillance endoscopy on overstretched services. All collaborators of UK RFA registry are acknowledged for their contributions to this work. 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-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