Brinder S. Mahon

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.

Cyst fluid carcinoembryonic antigen in the investigation of cystic neuroendocrine tumors of the pancreas.

o C 1 w fl i c c n t p r w c s s p l The most common types of pancreatic cysts are pseudocysts, serous cystadenomas, mucinous cystadenomas (MCAs), and intraductal papillary mucinous neoplasms (IPMNs). Of these types of cysts, only the mucinous lesions, MCAs and IPMNs, have malignant potential and therefore may warrant surgical resection. The ability to identify these mucinous lesions preoperatively is therefore important. An elevated cyst fluid carcinoembryonic antigen (CEA) concentration is arguably the most reliable indicator of a mucinous lesion.1 Other diagnostic clues are he morphological characteristics of the lesion: the presnce or absence of mucin or atypical cells in the cyst fluid. There are a number of other uncommon causes of ancreatic cystic lesions. These include lymphoepithelial ysts and cystic variants of neuroendocrine tumors or uctal adenocarcinoma of the pancreas. Because the dignosis is often unclear at the time of EUS, cyst fluid is ften sent for CEA analysis in these lesions as well. Howver, our understanding of the utility of CEA concentration n this setting is limited. A recent cases series of lymphoeithelial cysts suggested that cyst fluid CEA concentration ay be elevated, which in 3 cases led to an unnecessary esection.2 There is one reported case of a cystic neuroendocrine lesion with a high cyst fluid CEA concentration that also led to a pancreatic resection, which in this case was justified on the basis of the final pathology.3 We ished to review our experience of the usefulness of cyst uid CEA concentration in these rare nonmucinous cystic eoplasms of the pancreas.

PWE-144 Endoscopic ultrasound in the evaluation of liver hilar pathology

Introduction Liver hilar pathology has traditionally been challenging to investigate as histological diagnosis is often difficult to obtain. The diagnostic yield of existing techniques including ERCP is suboptimal. Patients have consequently been managed in the absence of histological diagnosis, with the attendant hazards, including potential metal stent placement or unwarranted surgery in the absence of malignant disease. Upto 15% of patients with suspected biliary malignancy who undergo surgery are found to have benign disease. The utility of endoscopic ultrasound has not been established and our study aims to evaluate the role of EUS in this setting. Methods This is a retrospective review of all patients with a hepatic hilar stricture and or mass, who were reviewed at the hepatobiliary multidisciplinary meeting between July 2006 and September 2011 and went on to have an EUS examination. Patients with presumed benign disease were followed until they underwent definitive surgery, or for 1-year with serial cross sectional imaging. Results 95 patients with hilar lesions underwent 114 EUS examinations. 67 (70%) patients were diagnosed to have malignant disease. 58 patients had biliary tarct cancer. EUS-FNA yielded a positive cytological diagnosis in 52 (78%) patients. In 15 patients EUS cytology was false negative. 28 patients were diagnosed with benign disease. Factors that predicted malignant disease at EUS examination included the presence of a bile duct associated mass lesion (p value 0.0001) and an EUS morphological diagnosis of cancer (p value 0.03). The presence of “pathological” lymph nodes was not statistically significant (p value 0.79). Sensitivity in obtaining a cytological diagnosis, accuracy in defining benign and malignant disease, specificity and negative predictive value of EUS were 78%, 85%, 100%, and 66% respectively. Metal stent insertion was contemplated in atleast two patients following cross sectional imaging but was abandoned after EUS confirmed the benign nature of their condition. Conclusion In the largest series to date we report high sensitivity (80%) for EUS cytology in the diagnosis of malignant disease and accuracy (85%) in distinguishing malignant from benign disease. EUS had a significant impact on the clinical management of our patients, including prevention of potential metal stent placement in atleast two patients who were eventually diagnosed with benign disease. Competing interests None declared. Reference 1. Fritscher-Ravens A, Broering DC, Knoefel WT, et al. EUS-guided FNA of suspected hilar cholangiocarcinoma in potentially operable patients with negative brush cytology. Am J Gastroenterol 2004;99:45–51.

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

Sa1081 Outcomes of Patients Who Fail Initial Endoscopic Therapy for Barrett's Related Neoplasia

Introduction Endoscopic therapy with Endoscopic mucosal resection (EMR) followed by Radiofrequency ablation (RFA) is now recommended as first line treatment for patients with Barrett’s oesophagus (BE) related neoplasia confined to the mucosa. Method We examine prospective data from the United Kingdom registry of patients undergoing RFA/EMR for BE neoplasia to examine eventual outcomes of patients who do not have disease reversal at 12 months. All patients were treated with a recommended 12 month treatment protocol where before RFA, visible lesions and nodularity were entirely removed by EMR. Thereafter patients underwent RFA every 3 months until all visible BE was ablated. Biopsies were taken at around 12 months to access for treatment success. Those with residual dysplasia at this stage were offered further treatment and analysed here. Patients with a minimum of 24 months follow up were reviewed. Results 283 patients (81% male, mean age 70 years, 72% HGD, 24% IMC, 4% LGD) completed the 12 month treatment protocol and the majority 90% (255 patients) had reversal of neoplasia (CR-D) at 12 months with 2–3 RFA treatments. Of these with CR-D only one patient has subsequently progressed to invasive cancer (31 months after treatment). 28 patients had refractory neoplasia and were offered further endoscopic treatment. In these CR-D has been achieved in 67% (19/28) after 1–3 RFA treatments and all are free of neoplasia at median follow up of 46 months form initiating treatment. 3 patients in this cohort of non-responders progressed to invasive disease and the remainder (n = 6) are undergoing on going treatment. Conclusion The majority of patients with BE neoplasia will achieve successful disease reversal within a structured 12 month treatment program. However in the few that have residual neoplasia at this stage further RFA can be successfully used to eradicate neoplasia. Surgery for those fit remains a definitive treatment choice for the minority who do not respond to initial treatment or progress to invasive disease despite further treatment. All collaborators of the UK RFA registry are acknowledged for their contributions to data collection for this work Disclosure of interest None Declared.

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.