Endoscopic radiofrequency ablation for Barrett's oesophagus with lowgrade dysplasia or no dysplasia

# Recommendations
This document partially replaces previous guidance on epithelial radiofrequency ablation for Barrett's oesophagus (NICE interventional procedure guidance 344 issued in May 2010). For more information see section 7.
Current evidence on the efficacy of endoscopic radiofrequency ablation for Barrett's oesophagus with lowgrade dysplasia is adequate provided that patients are followed up in the long term. There are no major safety concerns. Therefore, this procedure may be used in patients with Barrett's oesophagus with lowgrade dysplasia with normal arrangements for clinical governance, consent and audit or research.
Current evidence on the efficacy and safety of endoscopic radiofrequency ablation for Barrett's oesophagus with no dysplasia is limited in quality and quantity. Therefore, this procedure should only be used in patients with no dysplasia in the context of research.
Patient selection for endoscopic radiofrequency ablation for Barrett's oesophagus with lowgrade dysplasia should be done by a multidisciplinary team experienced in managing Barrett's oesophagus, as described in the British Society of Gastroenterology guidelines.
Endoscopic radiofrequency ablation for Barrett's oesophagus with lowgrade dysplasia should only be done by endoscopists experienced in treating Barrett's oesophagus, as described in the British Society of Gastroenterology guidelines.
Clinicians should enter details of all patients undergoing endoscopic radiofrequency ablation for Barrett's oesophagus with lowgrade dysplasia or no dysplasia onto the UK National HALO Patient Registry, and review clinical outcomes locally.
NICE encourages further research into endoscopic radiofrequency ablation for Barrett's oesophagus with no dysplasia. Studies should define clearly the policies used for histological diagnosis. Outcomes should include complete resolution of Barrett's oesophagus, change and progression to lowgrade dysplasia, highgrade dysplasia or cancer. All complications should be reported, particularly development of strictures. Comparative studies against surveillance would be useful.# Indications and current treatments
Barrett's oesophagus is a precancerous condition characterised by abnormal replacement of the squamous epithelium of the lower oesophagus by a type of columnar epithelium resembling that in the stomach and intestine.
In some patients, Barrett's oesophagus may progress through a series of stages to oesophageal adenocarcinoma  a cancer with a poor prognosis. These intermediate stages are graded into lowgrade and highgrade dysplasia according to the degree of abnormal cellular architecture.
The risk of progression to oesophageal adenocarcinoma for anyone with Barrett's oesophagus is difficult to predict accurately. In general, the risk of cancer is highest for patients with highgrade dysplasia, lower for patients with lowgrade dysplasia, and lowest for patients with no dysplasia (also referred to as 'intestinal metaplasia'  a change from epithelium that is normal for this site but with no evidence of dysplasia). Accurate classification of Barrett's oesophagus into these distinct histopathological types is difficult; there is the possibility of diagnostic misclassification because of biopsy sampling error and subjective biopsy interpretation. Strategies for addressing this include multiple biopsy sampling, diagnosis on at least 2 occasions, confirmation by 2 specialist histopathological experts and confirmation by an independent pathologist external to the original institution each time  all in the context of a multidisciplinary team.
The main risk factor for developing Barrett's oesophagus is a history of reflux of acid and/or bile into the oesophagus. Reflux commonly produces symptoms of heartburn but it can be asymptomatic.
The management of Barrett's oesophagus is determined by the dysplasia status. In Barrett's oesophagus with no dysplasia or lowgrade dysplasia, periodic endoscopic surveillance and repeat biopsies may be considered with the aim of early detection of progression to highgrade dysplasia or cancer. If highgrade dysplasia or early cancer (carcinoma in situ) is detected, then treatment is recommended. If the disease is superficial (confined to the mucosa), treatment can usually be done endoscopically.
Endoscopic treatments for Barrett's oesophagus aim to destroy the Barrett's epithelium, leaving a surface that is subsequently replaced with a normal squamous epithelium. If the Barrett's epithelium is flat, then it can be ablated using one of several possible modalities such as photodynamic therapy, argon plasma coagulation, laser ablation, cryotherapy or multipolar electrocoagulation. If there are visible abnormalities, such as nodules or ulcers, then those areas are usually removed by endoscopic resection.# The procedure
The procedure is usually carried out with the patient under conscious sedation, in an outpatient setting. Using endoscopic visualisation, an appropriately sized radiofrequency ablation probe attached to the endoscope is inserted into the oesophagus, and advanced to the target area. Controlled pulses of radiofrequency energy are delivered, which cause thermal ablation of a thin layer of epithelium in the affected areas. A circumferential ablation catheter is usually used for primary treatment, whereas a focal ablation catheter can be used for remaining patches of Barrett's epithelium in any subsequent treatments. Radiofrequency ablation can also be used after doing endoscopic resection to remove larger, superficial abnormal areas. If followup highdefinition endoscopy and rebiopsy show residual Barrett's changes, repeat treatment can be done using radiofrequency ablation.# Efficacy
This section describes efficacy outcomes from the published literature that the Committee considered as part of the evidence about this procedure. For more detailed information on the evidence, see the interventional procedure overview.

# Lowgrade dysplasia
A randomised controlled trial of 127 patients with nonnodular dysplastic Barrett's oesophagus (64 with lowgrade dysplasia and 63 with highgrade dysplasia) compared radiofrequency ablation plus endoscopic surveillance against endoscopic surveillance alone (sham procedure). Among patients with lowgrade dysplasia (n=64; 42 treated by radiofrequency ablation, 22 treated by sham procedure), complete eradication of dysplasia was reported in 91% (38/42) of patients treated by radiofrequency ablation, compared with 23% (5/22) treated by sham procedure at 12month followup. Patients randomised to the sham procedure were offered crossover to radiofrequency ablation after 12 months. After crossover, complete eradication of all dysplasia and intestinal metaplasia was reported in 98% (51/52) of patients with lowgrade dysplasia at 2year followup. At 3year followup, dysplasia was eradicated in 100% (32/32) of patients.
A randomised controlled trial of 136 patients with lowgrade dysplasia comparing radiofrequency ablation (n=68) against endoscopic surveillance (control, n=68) reported that the lowgrade dysplasia treated by radiofrequency ablation was less likely to progress to adenocarcinoma (2%  compared with 9% , p=0.03) and less likely to progress to highgrade dysplasia or adenocarcinoma (2%  compared with 27% , p<0.001) at 3year followup. At the end of the treatment, complete eradication of dysplasia and intestinal metaplasia occurred in 93% (63/68) and 88% (60/68) of patients respectively in the radiofrequency ablation group (data not given for the control group). During followup, complete eradication of dysplasia and metaplasia was maintained in 98% (62/63) and 90% (54/60) of patients respectively compared with 28% (19/68) (p<0.001) and 0% (p<0.001) of patients respectively in the control group.
The randomised controlled trial of 127 patients reported less progression from lowgrade dysplasia to highgrade dysplasia in patients treated by radiofrequency ablation (5% ) compared with those treated by sham procedure (14% , p=0.33) at 12month followup.

# No dysplasia
A case series of 102 patients with nondysplastic Barrett's oesophagus (32 in a dosimetry phase I study and 70 in an effectiveness phase II study) reported complete eradication of intestinal metaplasia in 59% (19/32) of patients in the dosimetry phase and 69% (48/69) of patients in the effectiveness phase at 12month followup. In the effectiveness phase study at 30month followup, after additional focal ablation in patients with endoscopic and histological evidence of intestinal metaplasia at 12month biopsy, complete eradication of intestinal metaplasia was reported in 97% (60/61) of patients. At 5year followup, complete eradication of intestinal metaplasia was reported in 92% (46/50) of patients, while 8% (4/50) of patients had intestinal metaplasia that was treated with 'single salvage focal ablation' 1 month after biopsy (complete eradication of intestinal metaplasia was reported at subsequent 2month biopsy).
The specialist advisers listed key efficacy outcomes as eradication of dysplasia, prevention of progression to cancer, eradication of intestinal metaplasia, eradication of Barrett's oesophagus and quality of life.# Safety
This section describes safety outcomes from the published literature that the Committee considered as part of the evidence about this procedure. For more detailed information on the evidence, see the interventional procedure overview.
Gastrointestinal haemorrhage was reported in 1 patient being treated by antiplatelet therapy for heart disease in the radiofrequency ablation group in a randomised controlled trial of 127 patients. This was treated endoscopically.
Perforation of the oesophagus (measuring 1.5 cm) within the proximal radiofrequency ablation field (noted 6 weeks postoperatively because of a report of 'a food impaction') was reported in 1 patient in a case series of 10 patients. Further details were not reported.
Oesophageal strictures were reported in 12% (8/68) of patients treated by radiofrequency ablation (time of occurrence not reported) in a randomised controlled trial of 136 patients: these were all successfully treated by endoscopic dilatation (in median of 1 session).
Erosive oesophagitis (transient and resolved completely) was reported in 6% (3/50) of patients at 5year followup in a case series of 70 patients.
Overnight hospitalisation for new chest pain was reported in 1 patient (8 days after radiofrequency ablation) in the radiofrequency ablation group in the randomised controlled trial of 127 patients (outcome not reported). Chest pain (transient and resolved spontaneously) was reported in 8% (9/106) of procedures in the case series of 70 patients.
Fever (transient and resolved completely) was reported in 2% (2/106) of procedures undertaken in the case series of 70 patients.
The specialist advisers listed additional adverse events as dysphagia and oesophageal laceration.# Further information
This guidance is a partial review of Epithelial radiofrequency ablation for Barrett's oesophagus (NICE interventional procedure guidance 344 issued in May 2010). It applies only to Barrett's oesophagus with lowgrade or no dysplasia. The sections in IPG344 relating to Barrett's oesophagus with highgrade dysplasia continue to apply.

# Information for patients
NICE has produced information on this procedure for patients and carers (Information for the public). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.# About this guidance
NICE interventional procedures guidance makes recommendations on the safety and efficacy of the procedure. It does not cover whether or not the NHS should fund a procedure. Funding decisions are taken by local NHS bodies after considering the clinical effectiveness of the procedure and whether it represents value for money for the NHS.
This guidance was developed using the NICE interventional procedures guidance process.
It partially replaces NICE interventional procedure guidance 344.
We have produced a summary of this guidance for patients and carers. Information about the evidence the guidance is based on is also available.
NICE produces guidance, standards and information on commissioning and providing highquality healthcare, social care, and public health services.  We have agreements to provide certain NICE services to Wales, Scotland and Northern Ireland.  Decisions on how NICE guidance and other products apply in those countries are made by ministers in the Welsh government, Scottish government, and Northern Ireland Executive. NICE guidance or other products may include references to organisations or people responsible for commissioning or providing care that may be relevant only to England.
Your responsibility
    This guidance represents the views of NICE and was arrived at after careful consideration of the available evidence. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. This guidance does not, however, override the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.
Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to have due regard to the need to eliminate unlawful discrimination, advance equality of opportunity and foster good relations. Nothing in this guidance should be interpreted in a way that would be inconsistent with compliance with those duties.
Copyright
     National Institute for Health and Care Excellence 2014. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and notforprofit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.
ISBN 9781473106420