Interventional procedure consultation document

Endoscopic radiofrequency ablation for Barrett’s oesophagus with low-grade dysplasia or no dysplasia

 

Barrett’s oesophagus is abnormal cells on the inside lining of the oesophagus (gullet). It may lead to cancer. In endoscopic radiofrequency ablation, the abnormal cells are destroyed by a coil-like device inserted through the mouth and into the oesophagus.

The National Institute for Health and Care Excellence (NICE) is examining endoscopic radiofrequency ablation for Barrett’s oesophagus with low-grade dysplasia or no dysplasia and will publish guidance on its safety and efficacy to the NHS. NICE’s Interventional Procedures Advisory Committee has considered the available evidence and the views of specialist advisers, who are consultants with knowledge of the procedure. The Advisory Committee has made provisional recommendations about endoscopic radiofrequency ablation for Barrett’s oesophagus with low-grade dysplasia or no dysplasia.

This document summarises the procedure and sets out the provisional recommendations made by the Advisory Committee. It has been prepared for public consultation. The Advisory Committee particularly welcomes:

• comments on the provisional recommendations
• the identification of factual inaccuracies
• additional relevant evidence, with bibliographic references where possible.

Note that this document is not NICE’s formal guidance on this procedure. The recommendations are provisional and may change after consultation.

The process that NICE will follow after the consultation period ends is as follows.

• The Advisory Committee will meet again to consider the original evidence and its provisional recommendations in the light of the comments received during consultation.
• The Advisory Committee will then prepare draft guidance which will be the basis for NICE’s guidance on the use of the procedure in the NHS.

For further details, see the Interventional Procedures Programme manual, which is available from the NICE website.

Through its guidance NICE is committed to promoting race and disability equality, equality between men and women, and to eliminating all forms of discrimination. One of the ways we do this is by trying to involve as wide a range of people and interest groups as possible in the development of our interventional procedures guidance. In particular, we aim to encourage people and organisations from groups who might not normally comment on our guidance to do so.

In order to help us promote equality through our guidance, we should be grateful if you would consider the following question:

Are there any issues that require special attention in light of NICE’s duties to have due regard to the need to eliminate unlawful discrimination, advance equality of opportunity, and foster good relations between people with a characteristic protected by the equalities legislation and others?

Please note that NICE reserves the right to summarise and edit comments received during consultations or not to publish them at all where in the reasonable opinion of NICE, the comments are voluminous, publication would be unlawful or publication would otherwise be inappropriate.

Closing date for comments: 18 April 2014

Target date for publication of guidance: July 2014

 

 

 

 

 

1                      Provisional recommendations

1.1                  Current evidence on the efficacy of endoscopic radiofrequency ablation for Barrett’s oesophagus with low-grade 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 low-grade dysplasia with normal arrangements for clinical governance, consent and audit or research.

1.2                  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.

1.3                  Patient selection for endoscopic radiofrequency ablation for Barrett’s oesophagus with low-grade dysplasia should be done by a multidisciplinary team experienced in the management of Barrett’s oesophagus, as described in the British Society of Gastroenterology guidelines.

1.4                  Endoscopic radiofrequency ablation for Barrett’s oesophagus with low-grade dysplasia should only be done by endoscopists with specific training in this procedure, as described in the British Society of Gastroenterology guidelines.

1.5                  Clinicians should enter details of all patients undergoing endoscopic radiofrequency ablation for Barrett’s oesophagus with low-grade dysplasia or no dysplasia onto the UK national HALO patient registry and review clinical outcomes locally.

1.6                  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 low-grade dysplasia, high-grade dysplasia or cancer. All complications should be reported, particularly development of strictures. Comparative studies against surveillance would be useful.

 

 

 

 

 

2                      Indications and current treatments

2.1                  Barrett’s oesophagus is a precancerous condition characterised by the abnormal replacement of the squamous epithelium of the lower oesophagus by a type of columnar epithelium resembling the stomach and intestine.

2.2                  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 low-grade and high-grade dysplasia according to the degree of abnormal cellular architecture.

2.3                  The risk of progression to oesophageal adenocarcinoma for any individual with Barrett’s oesophagus is difficult to predict accurately. In general, the risk of cancer is highest for patients with high-grade dysplasia, lower for patients with low-grade dysplasia, and lowest for patients with no dysplasia (also referred to as ‘intestinal metaplasia’; change of epithelium from normal at that site but involving no dysplasia). However, regression from high-grade dysplasia to low-grade dysplasia as well as from low-grade dysplasia to no dysplasia (intestinal metaplasia) is known to occur in some patients. In addition, accurate classification of Barrett’s oesophagus into these distinct histopathological types involves multiple biopsy sampling and specialist histopathological expertise. There is the possibility of diagnostic misclassification due to biopsy sampling error and subjective biopsy interpretation.

2.4                  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.

2.5                  The management of Barrett’s oesophagus is determined by the dysplasia status. In Barrett’s oesophagus with no dysplasia or low-grade dysplasia, periodic endoscopic surveillance and repeat biopsies are usually done with the aim of early detection of progression to high-grade dysplasia or cancer. If high-grade 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, without the need to remove the oesophagus.

2.6                  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 radiofrequency ablation, 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.

 

 

 

 

 

3                      The procedure

3.1                  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 (360^°) ablation catheter is usually used for primary treatment, whereas a focal (90°) ablation catheter can be used for remaining patches of Barrett’s epithelium in any subsequent treatments.  Radiofrequency ablation can also be used after performing endoscopic resection to remove larger, superficial abnormal areas. If follow-up endoscopy and re-biopsy show residual Barrett's changes, repeat treatment can be done using radiofrequency ablation.

 

 

 

 

 

4                      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.

                     Low-grade dysplasia

4.1                  A randomised controlled trial of 127 patients with non-nodular dysplastic Barrett’s oesophagus (64 with low-grade dysplasia and 63 with high-grade dysplasia) compared radiofrequency ablation  plus endoscopic surveillance against endoscopic surveillance alone (sham procedure). Among patients with low-grade 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 12 months’ follow-up. 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 low-grade dysplasia at 2‑year follow-up. After 3 years of follow up, dysplasia was eradicated in 100% (32/32) of patients.

4.2                  A randomised controlled trial of 136 patients with low-grade dysplasia comparing radiofrequency ablation (n=68) against endoscopic surveillance (control, n=68) reported that the low-grade dysplasia treated by radiofrequency  ablation was less likely to progress to adenocarcinoma (2% [1/68] compared with 9% [6/68], [p=0.026]) and less likely to progress to high-grade dysplasia or adenocarcinoma (2% [1/68] compared with 27% [18/68] [p<0.001]) at 3‑year follow-up. Complete eradication of dysplasia and intestinal metaplasia occurred in 93% and 88% of patients in the radiofrequency ablation group, compared with 28% and 0% (p<0.001) of patients in the control group respectively.

4.3                  The randomised controlled trial of 127 patients reported lower progression from low-grade dysplasia to high-grade dysplasia in patients treated by radiofrequency ablation (5% [2/42]) compared with those treated by sham procedure (14% [3/22], p=0.33) at 12‑month follow-up.

               No dysplasia

4.4                  A case series of 102 patients with non-dysplastic 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 12‑month follow-up. In the effectiveness phase study at 30‑month follow-up, after additional focal ablation in patients with endoscopic and histological evidence of intestinal metaplasia at 12‑month biopsy, complete eradication of intestinal metaplasia was reported in 97% (60/61) of patients. At 5‑year follow-up, 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 2‑month biopsy).

4.5                  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.

 

 

 

 

 

5                      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.

5.1                  Perforation of the oesophagus (measuring 1.5 cm) within the proximal radiofrequency ablation field (noted 6 weeks postoperatively due to report of ‘a food impaction’) was reported in 1 patient in the case series of 10 patients. Further details not reported.

5.2                  Oesophageal strictures were reported in 12% (8/68) of patients treated by radiofrequency ablation (time of occurrence not reported) in the randomised controlled trial of 136 patients: these were all successfully treated by endoscopic dilatation (in median of 1 session).

5.3                  Oesophageal strictures were reported in 8% (9/119) of patients treated by radiofrequency ablation (time of occurrence not reported) in the crossover cohort study of 119 patients. This was a follow-up of a multicentre randomised sham controlled trial of 127 patients. All were successfully treated by endoscopic dilatation (in mean of 2.6 sessions).

5.4                  Erosive oesophagitis (transient and resolved completely) was reported in 6% (3/50) of patients at 5‑year follow-up in the case series of 70 patients.

5.5                  Gastrointestinal haemorrhage was reported in 1 patient being treated by antiplatelet therapy for heart disease in the radiofrequency ablation group in the randomised controlled trial of 127 patients. This was treated endoscopically.

5.6                  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.

5.7                  Hospitalisation for nausea and chest discomfort immediately after radiofrequency ablation was reported in 1 patient in the crossover cohort study of 119 patients (outcome not reported). Nausea related to sedation (that resolved spontaneously) occurred in 8% (8/106) of procedures in the case series of 70 patients.

5.8                  Fever (transient and resolved completely) was reported in 2% (2/106) of procedures undertaken in the case series of 70 patients.

5.9                  The specialist advisers listed additional adverse events as dysphagia and oesophageal laceration.

 

 

 

 

 

6                      Committee comments

6.1                  The Committee noted the difficulties in reliable diagnosis of low-grade dysplasia and was advised about the benefits of consensus reporting of histology.

 

 

 

 

 

7                      Further information

7.1                  This guidance is a partial review of Epithelial radiofrequency ablation for Barrett’s oesophagus (NICE interventional procedure guidance 344, 2010). It applies only to Barrett’s oesophagus with low-grade or no dysplasia. Sections of IPG344 relating to Barrett’s oesophagus with high-grade dysplasia continue to apply.

 

 

Bruce Campbell
Chairman, Interventional Procedures Advisory Committee
March 2014

 

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