evidence note Radiofrequency ablation for Barrett s oesophagus with highgrade What is an evidence note Key points Literature search Introduction

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1 In response to an enquiry from the National Cancer Waiting Times Delivery Group What is an evidence note Evidence notes are rapid reviews of published secondary clinical and cost-effectiveness evidence on health technologies under consideration by decision makers within NHSScotland. They are intended to provide information quickly to support time-sensitive decisions and are produced in an approximately 3 month period. Evidence notes are not comprehensive systematic reviews. They are based on the best evidence that Healthcare Improvement Scotland could identify and retrieve within the time available. The reports are subject to peer review but do not undergo external consultation. Evidence notes do not make recommendations for NHSScotland. Literature search A literature search was conducted during January 2012 to identify relevant guidelines, health technology assessments (HTA), systematic reviews and primary studies, including economic evaluations. Database searches were limited to English language and publications from January 2009 to January Full details are available on request. Introduction This evidence note summarises published secondary evidence on the clinical effectiveness, safety and cost effectiveness of radiofrequency ablation (RFA) for the treatment of Barrett s oesophagus with high-grade dysplasia. Barrett s oesophagus is a condition in which the normal squamous epithelium lining the lower oesophagus undergoes transformation (metaplasia) to abnormal columnar epithelium characterised by gastric and intestinal cell types 1-3. In the United Kingdom (UK), Barrett s oesophagus is defined as any segment of endoscopically visible columnar-lined epithelium confirmed by biopsy evidence note Key points Number 45 July 2012 Radiofrequency ablation for Barrett s oesophagus with highgrade dysplasia The only published randomised controlled trial of radiofrequency ablation (RFA) for Barrett s oesophagus with dysplasia compared RFA with sham treatment. RFA achieved higher rates of eradication of intestinal metaplasia (77% versus 2%) and high grade dysplasia (HGD) (81% versus 19%) at 12 month follow up. Observational data from the RCT extension study indicate treatment effect durability and a low rate of disease progression up to 3 years after RFA. Evidence from the RCT and case series indicates that the risk of major complications and adverse events from RFA is low. Two distinct economic models, each examining a different set of comparators, were identified. A NICE economic model studied patients with Barrett s oesophagus with HGD or early intramucosal cancer, comparing a range of interventions alone or in combination, compared with no surveillance. The cost/quality adjusted life year (QALY) of endoscopic mucosal resection, followed by RFA and surveillance versus no surveillance was 15,916. The cost/ QALY of oesophagectomy versus no surveillance was 10,612. In another UK economic model in a hypothetical population of male patients with Barrett s oesophagus with HGD aged 64 years, RFA followed by surveillance dominated oesophagectomy (ie cost less and generated more QALYs). showing any type of metaplasia, gastric or intestinal 4,5. Barrett s oesophagus with intestinal metaplasia (IM) is the most common histological subtype 4. Complications of Barrett s oesophagus include oesophagitis, stricture and ulceration, but the main concern is the potential to progress to

2 evidence note 2 dysplasia and oesophageal cancer 1. Although the natural history of Barrett s oesophagus is not yet fully understood, the condition is thought to progress from metaplasia through low-grade dysplasia (LGD) and high-grade dysplasia (HGD) to invasive oesophageal adenocarcinoma 1-3,6,7. Health technology description The standard treatment for Barrett s oesophagus with HGD or intramucosal cancer is oesophagectomy (surgical excision of part of the oesophagus) 8. Oesophagectomy is a highrisk procedure with complications in 30 50% of patients 7 and a 30-day mortality rate of 3.2% (95% confidence interval (CI) 2.3 to 4.5) 9. Less invasive endoscopic techniques including endoscopic mucosal resection and ablative treatments offer alternatives for patients who are unsuitable for surgery or who prefer less invasive treatment 8. Endoscopic approaches aim to remove or ablate the abnormal Barrett s epithelium to allow re-epithelialisation with normal squamous epithelium (neosquamous epithelium) 2. RFA is an endoscopic ablative procedure performed under conscious sedation, usually in the outpatient setting, by a gastroenterologist or surgical endoscopist 10,11. The technique involves direct application of short (<1 second) pulses of thermal energy that destroy abnormal epithelium to a depth of <1 mm 10,12. Currently available devices allow circumferential ablation of larger segments ( 3 cm) using a catheter with a 360 electrode array (HALO360, BÂRRX Medical, Sunnyvale, California) and focal ablation of smaller segments (<2 cm) using a bipolar electrode array mounted on the tip of a gastroscope (HALO90, ibid) 2,10. The ablation procedure involves two separate applications of thermal energy and removal of coagulated tissue between the first and second application 2,13. Treatment may be repeated if follow-up endoscopy shows residual Barrett s oesophagus 10. RFA can be used alone or following endoscopic mucosal resection to remove visible lesions 2,7. Contraindications to RFA include pregnancy, prior radiation to the oesophagus, Heller myotomy surgery, eosinophilic oesophagitis and oesophageal varices 10. Epidemiology Barrett s oesophagus is prevalent in % of the adult population in the UK 14 with around 60,000 new cases per year (annual incidence around 0.1%) 6. In around 60% of cases, Barrett s oesophagus is associated with chronic gastro-oesophageal reflux, which is a major risk factor 6. Barrett s oesophagus is found in 15 20% of adults undergoing endoscopic investigation of symptomatic chronic reflux 3,8,10. The condition can, however, develop in the absence of symptoms and only 5 10% of adults with reflux develop Barrett s oesophagus 3,6,7. Other factors associated with increased risk of developing Barrett s oesophagus are Caucasian race, male sex, and older age 1,6,7. The evidence of association of risk with alcohol, obesity and Helicobacter pylori infection is, however, inconsistent 1. Men with Barrett s oesophagus have an absolute lifetime risk of developing oesophageal adenocarcinoma of about 5% compared with 3% for women 1. In studies of patients with Barrett s oesophagus with HGD undergoing surveillance, approximately six patients per 100 patient-years develop oesophageal adenocarcinoma 15. The combined incidence of HGD and oesophageal adenocarcinoma in patients under surveillance is estimated to be higher in the UK (13.0/1,000 patient-years; 95% CI 7.4 to 22.8) than in other European countries (7.3/1,000 patient-years; 95% CI 3.6 to 15.0) 16. The rate of progression to cancer among patients with Barrett s oesophagus in the UK as a whole is approximately 1% per year 14. In the west of Scotland, however, the rate of 16 cases of oesophageal adenocarcinoma related to Barrett s oesophagus per 100,000 population is reportedly higher than anywhere else in the world 6. A recent review of Barrett s oesophagus in the west of Scotland indicated that the rate of cancer progression is about eight times greater than elsewhere in Europe (G Fullarton, Consultant Oesophago-Gastric Surgeon, NHS Greater Glasgow and Clyde. Personal communication, 6 June 2012).

3 evidence note 3 The average risk of mortality attributable to oesophageal adenocarcinoma among Barrett s oesophagus patients under surveillance has been estimated at 0.3% per year (incidence 3.0/1,000 patient-years; 95% CI 2.2 to 3.9) 16. Oesophageal adenocarcinoma has a poor prognosis with 5-year survival rates in Scotland of 10% for men and 11% for women 17 Safety The National Institute for Health and Clinical Excellence (NICE) updated its interventional procedure guidance on epithelial RFA for Barrett s oesophagus in May The guidance committee considered evidence from a rapid review of literature published to January The review included the multicentre Ablation of Intestinal Metaplasia containing Dysplasia (AIM Dysplasia) randomised control trial (RCT) comparing RFA with a sham procedure in patients with Barrett s oesophagus with LGD (n=64) or HGD (n=63), two registry studies and six case series ( ) including a total of 581 patients 18. The guidance cited data from the RCT, the registry studies and two case series 11. In the RCT, 5/84 (6%) patients in the RFA group experienced oesophageal stricture compared with none (0/43) in the sham-treatment control group 4,11,18. One patient developed new-onset chest pain and another experienced chest discomfort and nausea following RFA, both requiring overnight hospitalisation 11. A UK registry of 106 patients recorded eight new strictures 11. Buried glandular mucosa (metaplasia underneath neosquamous epithelium) was detected during endoscopic biopsy surveillance in 4/27 (15%) patients in one case series, and in 1/1,475 biopsies from a series of 44 patients 11. The guidance concluded that there were no major safety concerns 11. A subsequently published extension of the AIM Dysplasia trial examined outcomes beyond 1 year 19. Participants randomised to the sham procedure group were offered crossover to RFA after the 1-year RCT outcomes evaluation, and all RFA-treated patients were followed up for 2 years post-treatment. Patients with complete eradication of IM at 2 years (or salvaged with a single additional RFA treatment) were eligible to enter the extension study entailing an additional 3-year follow up. Overall, 119 patients received RFA (84 in the RCT plus 35 crossover), 106 completed 2-year follow up, and 100 entered the extension study. The mean follow-up duration was 3.05 years (standard deviation (SD) 1.08). At the time of reporting, 56 patients (24 HGD, 32 LGD) had completed 3-year follow up. There were no perforations or procedure-related deaths. Three of the 119 patients required overnight hospitalisation: one for new-onset chest pain; two for chest discomfort and nausea. One patient receiving dual antiplatelet therapy for heart disease suffered upper gastrointestinal haemorrhage. Oesophageal stricturing occurred in 9/119 patients (7.6%) 19. A systematic review of nine case series of RFA for Barrett s oesophagus with at least 12-months follow up (n=429) reported no serious adverse events 20. The most common adverse events reported were chest and throat pain, sedation-related nausea and fever, and odynophagia (pain on swallowing) 20. One study (n=54) reported strictures in four patients whose Barrett s oesophagus segment length at baseline was 6 cm (one patient) and >12 cm (three patients) 20. The included studies provided data on over 8,500 follow-up biopsies, of which only one study reported one case of buried Barrett s metaplasia 20. Another systematic review reported buried metaplasia detected on follow-up biopsy of neosquamous epithelium after RFA in 9/1,004 (0.9%) patients in 18 studies, including four patients in the AIM Dysplasia RCT, with follow up ranging from 8 weeks to 5 years 21. The review found no reports of neoplasia in buried metaplasia following RFA 21. The available evidence was, however, limited by inadequate reporting on the adequacy of biopsy and short duration of follow up 21. A recent technology assessment concluded that the literature available indicated that RFA was a safe treatment for Barrett s oesophagus with dysplasia and/or early intramucosal cancer, with few major complications 12. The authors did, however, note the paucity of data directly comparing the safety of RFA with alternative interventions 12.

4 evidence note 4 Clinical effectiveness NICE interventional procedure guidance on epithelial RFA for Barrett s oesophagus cited efficacy data from the AIM Dysplasia RCT comparing RFA with a sham procedure, and one registry study 11. In the RCT, complete eradication of IM at 12-month follow up was achieved in 77% (65/84) in the RFA group compared with 2% (1/43) in the sham-procedure control group (risk ratio (RR)=33.3; 95% CI 4.8 to 231.7; p<0.001) 11,22. Complete eradication of dysplasia was also significantly greater with RFA for both LGD (38/42 versus 5/22; p<0.001) and HGD (34/42 versus 4/21; p<0.001) 18,22. Fewer RFA patients with HGD progressed to cancer at 12-month follow up compared with the control group (1/42 versus 4/21; RR=0.1; 95% CI 0.01 to 1.0; p=0.04). The trial showed no difference between groups in progression from LGD to HGD, or from LGD to cancer 18. The registry of patients with IM with HGD and at least one post-rfa follow-up endoscopy with biopsies reported eradication of HGD in 83/92 (90%), eradication of all dysplasia (HGD and LGD) in 74/92 (80%), and eradication of IM in 50/92 (54%) at a median follow up of 1 year 11. The guidance concluded that the evidence on the efficacy of epithelial RFA in patients with Barrett s oesophagus with HGD was adequate, provided that patients are followed up in the long term 11. The procedure may, therefore, be used provided that normal arrangements are in place for clinical governance, consent and audit 11. NICE clinical guidelines on ablative therapy for the treatment of Barrett s oesophagus with HGD or early intramucosal cancer also considered the aforementioned RCT and registry study to inform recommendations on the use of RFA alone 8. The quality of the RCT was deemed to be high, and that of the registry study very low 8. The guideline recommended consideration of RFA (or photodynamic therapy (PDT)) alone for flat HGD 8. Evidence from five uncontrolled case series was reviewed to inform recommendations on ablative therapies in combination with endoscopic mucosal resection 8. Despite very low-quality evidence, the guideline group recommended consideration of additional ablative therapy (RFA, PDT or argon plasma coagulation (APC)) following endoscopic mucosal resection to completely remove flat dysplasia 8. Cochrane systematic reviews have failed to identify additional relevant RCTs 4,23. A systematic review of nine published ( ) case series with at least 12 months of follow up (n=429) showed that eradication of IM ranged from % of cases in seven studies that used stepwise circumferential and focal ablation and 46 54% in two studies using only circumferential ablation 20. Four studies that used circumferential and focal ablation in patients with dysplasia reported eradication of dysplasia in % of cases, whereas two studies using only circumferential ablation reported eradication in 71 80% 20. The review authors concluded that the results were promising but called for well-designed comparative studies 20. A recent technology assessment concluded that the limited evidence available suggested that RFA was effective with regard to histological eradication of IM and dysplasia at the mucosal level 12. The subsequently published AIM Dysplasia trial extension study examined the longer term durability of neosquamous epithelium and disease progression following RFA 19. Of the 106 RFA-treated patients (54 HGD, 52 LGD) who completed 2-year follow up, IM was eradicated in 48/54 (89%) patients with initial HGD, and dysplasia was eradicated in 50/54 (93%) patients. Among the 56 patients (24 HGD, 32 LGD) who had completed 3-year follow up, IM was eradicated in 51/56 (91%) and dysplasia in 55/56 (98%) (HGD not reported separately). Kaplan-Meier analysis indicated that >75% of HGD patients with complete eradication of IM 1 year or later post-rfa remained free of IM at a mean follow up of 3.05 years (SD 1.08) without additional treatment. Similarly, >85% of HGD patients with complete eradication of dysplasia 1 year or later post-rfa remained free of dysplasia 19. The annual rate of any disease progression (LGD to HGD or oesophageal cancer; or HGD to oesophageal cancer) was 1 per 73 patient-years (1.37% per patient per year). For comparison, the progression rate at 1 year in the sham procedure control group in the RCT was 1 per 6 patient-years (16.3% per patient per year). The rate of progression to

5 evidence note 5 oesophageal adenocarcinoma was 1 per 181 patient-years (0.55% per patient per year) overall, and 1 per 166 patient-years (0.60% per patient per year) among patients with initial HGD. Extended follow up to 5 years is ongoing 19. The impact of RFA on quality of life was assessed in patients who completed 12-month follow up in the AIM Dysplasia RCT (RFA n=77, sham n=35) 24. A questionnaire developed by the investigators (and not fully validated) showed statistically significant differences in the mean change from baseline on a visual analogue scale for cancer and oesophagectomy worry (p 0.001), depression (p=0.02), daily quality of life (p=0.009), stress (p=0.03), satisfaction (p 0.001), and impact of work or family life (p=0.02) in favour of RFA 24. No other published studies of quality of life were identified. Cost effectiveness Two published economic evaluations with an NHS perspective were identified 8,25. NICE undertook a cost-utility analysis to support clinical guidelines on ablative therapy for Barrett s oesophagus with HGD or early intramucosal cancer 8. A Markov model was constructed to compare endoscopic mucosal resection, ablation therapy (RFA, PDT and APC), and any combination of endoscopic mucosal resection and ablation therapy, with surgery (full oesophagectomy), surveillance and no surveillance in a population of 60-year-old adults 8. The comparators reflected British Society of Gastroenterologists and British Thoracic Surgeons Guidelines (sic) recommending surveillance and optional preventative surgery, and the fact that surveillance is not consistently offered across the NHS 8. Complications including perforation and stricture were included in the model. Postablative treatment surveillance lasted 5 years (every 3 months for the first year, every 6 months for the second year and then annually for the next 3 years) after which standard surveillance was implemented for patients with non-dysplastic Barrett s oesophagus (every 2 years), LGD (every 6 months) or HGD (every 3 months) 8. The model incorporated retreatment for recurrence of HGD following RFA, and oesophagectomy as treatment for oesophageal cancer 8. A published technology assessment provided the basis for the model and the transition probabilities between health states, some of which were updated from more recent publications 8. Clinical effectiveness data were derived from single RCTs for RFA (AIM Dysplasia trial) and PDT, and from individual case series for the other interventions. The effectiveness outcomes used in the model were complete ablation of dysplasia and complete ablation of Barrett s oesophagus. The guideline development group reduced the published estimate of complete ablation of dysplasia for endoscopic mucosal resection from 99% to 85% to better represent its effectiveness in the NHS setting. Perforations, strictures (and photosensitivity reactions) were the only adverse events included in the model with cost and quality-of-life outcomes. Utilities were obtained from published sources. Procedure costs were obtained from NHS reference costs, drug costs from the British National Formulary, and palliative care costs from published papers. The model assumed that HGD and intramucosal cancer were the same because clinically they would be treated in the same way 8. The model had a lifetime (50-year) time horizon and assumed no drop out from surveillance. Benefits were expressed as quality adjusted life years (QALYs), and incremental costeffectiveness ratios (ICERs) were calculated for each treatment compared with no surveillance. Comparing across treatments was considered inappropriate because most of the clinical data were from case series with heterogeneous populations. Deterministic and probabilistic sensitivity analyses were performed to account for uncertainty in costs and utilities 8. In the base-case analysis, compared with no surveillance, the ICERs were: 35,277 for surveillance alone 5,560 for surgery 13,846 for endoscopic mucosal resection and surveillance 24,829 for RFA and surveillance, and

6 evidence note 6 13,990 for endoscopic mucosal resection and RFA and surveillance 8 (The results for PDT and APT are not reported here.) Probabilistic sensitivity analysis showed that uncertainty around the value of ablative treatments with surveillance was driven by the uncertainty around the value of surveillance rather than the treatments. Given the poor quality of the evidence available, the probabilistic estimates of cost effectiveness were considered to be more reliable. Compared with no surveillance, the probabilistic ICERs were: 283,009 for surveillance alone 10,612 for surgery 25,662 for endoscopic mucosal resection and surveillance 24,823 for RFA and surveillance, and 15,916 for endoscopic mucosal resection, RFA and surveillance 8. The probability of RFA followed by surveillance being cost effective was 53.4% at 30,000 per QALY, and 39% at 20,000 per QALY; and for endoscopic mucosal resection plus RFA and surveillance, it was 70% at 30,000 per QALY and 55.4% at 20,000 per QALY 8. Bodger et al. published a subsequent costutility analysis with an NHS perspective based on a Markov model, comparing RFA followed by endoscopic surveillance with immediate oesophagectomy in a hypothetical cohort of 64-year-old men with Barrett s oesophagus with uni- or multifocal HGD 25. The model assumed that visible nodules, masses or surface irregularities had been removed by endoscopic mucosal resection 25. Complications including perforation and stricture were included in the model. Oesophagectomy patients were followed up for 5 years (every 3 months for 1 year, every 6 months for 2 years, and annually for 2 years). Post-RFA surveillance comprised annual endoscopy for 5 years for neosquamous oesophagus (and no further follow up if free of Barrett s oesophagus thereafter), and if Barrett s oesophagus persisted, annual endoscopy for 5 years then 2-yearly endoscopy if free of HGD or worse. Recurrence or persistence of HGD or oesophageal adenocarcinoma was treated by oesophagectomy 25. Clinical-effectiveness data were derived from published literature. Transition probabilities and utilities were also obtained from published literature, with unknown utility values estimated by consensus. The cost of RFA was estimated from information obtained from the UK distributor of the technology, and most other costs were estimated from NHS reference costs. All costs were for All costs and benefits were discounted at 3.5% as recommended by NICE. The model had a 25- year time horizon with outcomes expressed as QALYs. Deterministic and probabilistic sensitivity analyses and scenario analyses were performed to account for uncertainty 25. In the base-case analysis, the expected gains and associated costs for the RFA strategy were 14.2 QALYs and 6,653 compared with 13.8 QALYs and 8,555 for immediate oesophagectomy, hence RFA was dominant (ie cost less and generated more QALYs than oesophagectomy). The RFA strategy also resulted in less morbidity (20.8% versus 87.1%), procedure-related mortality (0.4% versus 2.6%) and cancer deaths (0.5% versus 1%) 25. One-way sensitivity analysis indicated that eradication of HGD post-rfa, and utility in the post-rfa with squamous oesophagus and fully recovered post-oesophagectomy states were key areas of uncertainty. At a willingness to pay of 30,000 per QALY, however, RFA remained cost effective even if HGD eradication was achievable in only 60% of cases, although the longest follow up available was a median of 2 years 25. Varying utility values indicated that fully recovered post oesophagectomy would have to be a more preferable health state than post RFA with squamous oesophagus in order for oesophagectomy to become a more effective (but still more costly) option than RFA. Altering other variables including age (55 70 years), discount rate (1 5%), and follow-up duration (5 30 years), did not substantially change the results of the model 25. A threshold analysis of uncertainty in the robustness of neosquamous epithelium following RFA indicated that a 20% annual risk of HGD recurrence would be required to

7 evidence note 7 change the results of the model. In a scenario analysis of continuing endoscopy surveillance for neosquamous oesophagus and Barrett s oesophagus at 2-yearly intervals after the initial annual endoscopy for 5 years, RFA still dominated oesophagectomy 25. Probabilistic analysis showed the probability of the RFA strategy being cost effective across a willingness to pay of 20,000 30,000 per QALY was approximately 84 86% 25. Bodger et al. noted that RFA with surveillance was considerably more expensive than oesophagectomy in the NICE evaluation, but not in their model 25. They posited that the inclusion of the cost of proton pump inhibitors in the post-rfa strategy but not in the postoesophagectomy strategy biased the NICE model in favour of oesophagectomy 25. Conclusion RFA for Barrett s oesophagus carries a low risk of major complications. RFA alone or in combination with endoscopic mucosal resection achieves high rates of eradication of IM and dysplasia in patients with Barrett s oesophagus with HGD. The evidence base consists mainly of case series as RFA has been evaluated in only one sham treatmentcontrolled RCT with a 12-month follow up. Three-year follow up of RFA-treated patients in the RCT extension study showed treatmenteffect durability and a low rate of disease progression. There is limited evidence on the impact of RFA on quality of life. Evidence from two economic evaluations suggests that RFA could be a cost-effective option for Barrett s oesophagus with HGD in the UK, but considerable uncertainty remains around the expected incremental costs and benefits compared with alternative management strategies. Equality and diversity Healthcare Improvement Scotland is committed to equality and diversity in respect of the nine equality groups defined by age, disability, gender reassignment, marriage and civil partnership, pregnancy and maternity, race, religion, sex, and sexual orientation. The evidence note process has been assessed and no adverse impact across any of these groups is expected. The completed equality and diversity checklist is available on About evidence notes For further information about the evidence note process, see To propose a topic for an evidence note, evidencenotes.hcis@nhs.net References can be accessed via the internet (where addresses are provided), via the NHS Knowledge Network or by contacting your local library and information service. Acknowledgements Healthcare Improvement Scotland would like to acknowledge the helpful contribution of the following, who gave advice on the content of this evidence note: Mr Grant M Fullarton, Consultant Oesophago-Gastric Surgeon, NHS Greater Glasgow and Clyde Healthcare Improvement Scotland development team Heather McIntosh, Author/Health Services Researcher Joanna Kelly, Literature search/health Services Researcher Emma Riches Medical Writer Doreen Pedlar, Project Co-ordinator Marina Tudor, Team Support Adminstrator Healthcare Improvement Scotland 2012 ISBN

8 evidence note 8 References 1. DynaMed. Barrett esophagus. Ipswich (MA): EBSCO Publishing; Repaka A, Chak A. Endoscopic management of Barrett esophagus. Nat Rev Gastroenterol Hepatol. 2011;8(10): Wild CP, Hardie LJ. Reflux, Barrett's oesophagus and adenocarcinoma: burning questions. Nat Rev Cancer. 2003;3(9): Rees JRE, Lao-Sirieix P, Wong A, Fitzgerald RC. Treatment for Barrett's oesophagus [cited 2012 Jul 10]; Available from: 5. British Society of Gastroenterology. Guidelines for the diagnosis and management of Barrett's columnar-lined oesophagus: a report of the working party of the British Society of Gastroenterology [cited 2012 Jul 10]; Available from: 6. Jankowski J, Barr H, Wang K, Delaney B. Diagnosis and management of Barrett's oesophagus. BMJ. 2010;341:c Sharma P. Clinical practice: Barrett's esophagus. N Engl J Med. 2009;361(26): National Institute for Health and Clinical Excellence. Barrett's oesophagus: ablative therapy for the treatment of Barrett's oesophagus. Guideline number [cited 2012 Jul 10]; Available from: 9. Palser T, Cromwell D, van der Meulen J, Hardwick R, Riley S, Greenaway K, et al. National oesophago-gastric cancer audit [cited 2012 Jul 10]; Available from: OESOPHAGO-GASTRIC%20CLINICAL%20AUDIT%20FINAL%20ART%20PDF%20no%20 logo.pdf 10. ECRI. Endoscopic radiofrequency ablation for Barrett's esophagus. Plymouth Meeting, PA: ECRI; National Institute for Health and Clinical Excellence. Epithelial radiofrequency ablation for Barrett's oesophagus. Interventional procedure guidance [cited 2012 Jul 10]; Available from: Gurgacz S, Church J, Cameron A, Goodall S. Radiofrequency ablation for Barrett's oesophagus with dysplasia [cited 2012 Jul 10]; Available from: Chennat J, Waxman I. Endoscopic treatment of Barrett's esophagus: from metaplasia to intramucosal carcinoma. World J Gastroenterol. 2010;16(30): Jankowski JA. Barrett esophagus and surveillance in the United Kingdom. Gastroenterol Hepatol. 2009;5(11): Rastogi A, Puli S, El-Serag HB, Bansal A, Wani S, Sharma P. Incidence of esophgeal adenocarcinoma in patients with Barrett's esophagus and high-grade dysplasia: a metaanalysis. Gastrointest Endosc. 2008;67(3): Sikkema M, de Jonge PJ, Steyerberg EW, Kuipers EJ. Risk of esophageal adenocarcinoma and mortality in patients with Barrett's esophagus: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2010;8(3):

9 evidence note 9 References continued 17. Information Services Division (ISD) Scotland. Cancer survival in Scotland [cited 2012 Jul 10]; Available from: Publications/ / Cancer-Survival-in-Scotland-report. pdf? National Institute for Health and Clinical Excellence. Interventional procedure overview of epithelial radiofrequency ablation for Barrett's oesophagus [cited 2012 Jul 10];. Available from: Shaheen NJ, Overholt BF, Sampliner RE, Wolfsen HC, Wang KK, Fleischer DE, et al. Durability of radiofrequency ablation in Barrett's esophagus with dysplasia. Gastroenterology. 2011;141(2): Semlitsch T, Jeitler K, Schoefl R, Horvath K, Pignitter N, Harnoncourt F, et al. A systematic review of the evidence for radiofrequency ablation for Barrett's esophagus. Surg Endosc. 2010;24(12): Gray NA, Odze RD, Spechler SJ. Buried metaplasia after endoscopic ablation of Barrett's esophagus: a systematic review. Am J Gastroenterol. 2011;106(11): Shaheen NJ, Sharma P, Overholt BF, Wolfsen HC, Sampliner RE, Wang KK, et al. Radiofrequency ablation in Barrett's esophagus with dysplasia. N Engl J Med. 2009;360(22): Bennett C, Green S, Barr H, Bhandari P, DeCaestecker J, Ragunath K, et al. Surgery versus radical endotherapies for early cancer and high grade dysplasia in Barrett's oesophagus [cited 2012 Jul 10]; Available from: Shaheen NJ, Peery AF, Hawes RH, Rothstein RI, Spechler SJ, Galanko JA, et al. Quality of life following radiofrequency ablation of dysplastic Barrett's esophagus. Endoscopy. 2010;42(10): Boger PC, Turner D, Roderick P, Patel P. A UK-based cost-utility analysis of radiofrequency ablation or oesophagectomy for the management of high-grade dysplasia in Barrett's oesophagus. Aliment Pharmacol Ther. 2010;32(11-12):