Endoscopic advances in the treatment of dysplastic Barrett oesophagus — should HALO be canonised or do we need more evidence?

Barrett oesophagus is a precursor lesion that can progress to oesophageal adenocarcinoma. Barrett oesophagus affects about 1% of the population and is believed to be due to chronic gastro-oesophageal reflux disease.1 Patients with Barrett oesophagus have a 30–40-fold relative risk of developing oesophageal adenocarcinoma, which usually occurs via progression through low-grade dysplasia (LGD) to high-grade dysplasia (HGD).2

Management of patients with non-dysplastic Barrett oesophagus comprises surveillance endoscopy and biopsies every 2–3 years, along with acid suppression. The traditional approach for treating LGD has been intensified endoscopic surveillance.

A new trend has evolved in the management of patients with HGD and intramucosal cancer. Oesophagectomy has been standard treatment for these patients because of studies showing that cancer is discovered in about 40% of oesophagectomy specimens after a preoperative diagnosis of HGD.3 Oesophagectomy in high-volume centres now carries a mortality rate of around 1%; however, morbidity rates can be up to 30%.4 Recently, improved capacity to identify early cancers with modern endoscopes and advances in endoscopic resection and ablation techniques have resulted in excellent outcomes for individuals with HGD and intramucosal cancer treated with endoscopy alone.

Staging dysplastic Barrett oesophagus requires meticulous endoscopic assessment, using the newest generation of high-definition endoscopes to identify nodules and subtle mucosal abnormalities that can harbour cancer. Biopsy samples are taken from visible abnormalities, and four-quadrant biopsy samples are taken from every 1 cm of Barrett oesophagus. New endoscopic technologies, such as narrow band imaging and confocal endomicroscopy, appear to aid identification of dysplastic areas and may reduce the need for random biopsies.

Endoscopic mucosal resection is a technique to remove 10–15 mm areas of mucosa, to the depth of the submucosa. Larger areas, or the entire Barrett oesophagus up to 3–5 cm in length, can be completely removed by this method with several contiguous resections. Endoscopic mucosal resection of focal mucosal abnormalities is essential to identify and remove early cancers and to determine the depth of invasion. If dysplasia or cancer is confined to the mucosal layer, the chance of spread to perioesophageal lymph nodes is less than 5%. On the other hand, if cancer extends into the submucosal layer, the chance of lymph node involvement is about 30% and oesophagectomy is therefore indicated.5,6

In expert hands, focal endoscopic mucosal resection achieved complete removal of HGD and intramucosal cancer in 96% of 231 patients.7 However, metachronous lesions occurred in 22% of patients at mean follow-up of 61 months; incomplete removal of the residual Barrett oesophagus was the main risk factor for recurrence. This highlights the importance of removal of the entire Barrett segment.7 To address this issue, a few European centres have advocated stepwise complete resection of short segments of Barrett oesophagus. In a recent multicentre study, complete eradication of all neoplasia was achieved in 98% of patients (165/169) after median follow-up of 32 months.8

Endoscopic mucosal resection has a 1% risk of serious complications, such as major bleeding or perforation. Symptomatic stenosis requiring dilatation develops in up to 50% of patients following stepwise complete resection.9

Endoscopic ablation therapies rely on the fact that squamous mucosa will replace the ablated Barrett oesophagus in a non-acid environment. Older endoscopic therapies include argon plasma coagulation, photodynamic therapy and multipolar electrocoagulation. These techniques are limited by variable mucosal ablation and “buried Barrett” under squamous mucosa.

The HALO radiofrequency ablation system (Barrx Medical, Sunnyvale, Calif, USA) consists of two devices for delivering radiofrequency energy to the Barrett oesophagus. The HALO360 device is a balloon that is inflated in the oesophagus to deliver a 3 cm circumferential burn, which can be repeated to treat long segments. The HALO90 is a flat device attached to the tip of the endoscope to ablate smaller areas of Barrett oesophagus. Energy delivery is automated, leading to a more predictable and uniform ablation, enhancing safety and efficacy compared with other ablative therapies.

A randomised controlled trial of HALO radiofrequency ablation compared with a sham procedure has shown much higher rates of complete remission after 12 months in individuals with HGD (81%) and LGD (91%) compared with the control groups.10 The 2–3-year follow-up of patients who remained in the study has confirmed durability of response, with 95% of patients who achieved complete remission of Barrett oesophagus at 12 months remaining so at 2 years. Furthermore, 85% of those who failed to eradicate Barrett oesophagus at 12 months achieved complete eradication at 2 years with a mean of 1.2 further focal ablation sessions. Longer-term follow-up beyond 5 years is required to address maintenance of remission and reduction in cancer progression.10

The principle of combination therapy is to remove visible mucosal abnormalities that may harbour invasive cancer with endoscopic mucosal resection, then to ablate the remaining Barrett oesophagus with HALO radiofrequency ablation. Using this approach, 22 of 23 patients with early cancer or HGD achieved complete remission of Barrett oesophagus, with no neoplasia recurrence after 22 months.11

Endoscopic therapy with HALO radiofrequency ablation and/or endoscopic mucosal resection has now emerged as a credible alternative to surgical oesophagectomy and should be considered as a valid alternative to surgery for patients with HGD and intramucosal cancer. Our institution favours the combination endoscopic approach.

The optimal management of patients with dysplastic Barrett oesophagus requires meticulous assessment and an individualised approach. Patients who undergo endoscopic therapy will need to be informed, motivated and compliant, as careful endoscopic surveillance after eradication is required to ensure that any recurrence is detected and treated early. Therefore, endoscopic therapy is best performed at tertiary centres with expertise in this evolving area.