© Georg Thieme Verlag KG Stuttgart · New York
Reflux and Barrett’s disease
23 October 2009 (eFirst)
Radiofrequency ablation in Barrett’s esophagus with dysplasia (Shaheen et al., N Engl J Med 2009 )
This randomized, sham-controlled trial investigated the efficacy of radiofrequency ablation (RFA) in eradicating Barrett’s dysplasia and preventing progression of disease. Various uncontrolled trials have been done in the past that have confirmed the safety and beneficial effects of RFA in eradicating dysplasia and intestinal metaplasia  . This study included 127 patients, 64 with low-grade dysplasia (LGD) and 63 with high-grade dysplasia (HGD), from 19 different centers in the USA. Patients were randomized in a stratified fashion to receive either RFA or a sham procedure in a 2 : 1 proportion. The primary outcome variables were complete eradication of dysplasia in the LGD and HGD groups as well as eradication of specialized intestinal metaplasia (SIM) at 12 months. Secondary outcomes included progression of disease, histologic eradication of SIM, discomfort level of patients, and adverse events. A maximum of four ablation sessions were offered in the treatment group and regular histologic analyses were performed.
Included patients had a maximum of 8 cm of Barrett’s esophagus, unlike an earlier study that included patients with up to 12 cm of Barrett’s . Nevertheless, multivariate analysis did not show any statistical significance for length of the Barrett’s segment in predicting response. A total of 11 patients had undergone previous endoscopic mucosal resection (EMR); however, at the time of randomization, none of the patients had visible mucosal lesions. Complete eradication of dysplasia was achieved in 86 % (92 % for per protocol analysis) with no statistical differences between the LGD and HGD groups. Total eradication of SIM was achieved in 77 % (83 % for per protocol analysis), again, irrespective of the grades of dysplasia. These results are comparable to a recently published uncontrolled trial, even though most patients in that study had EMR followed by RFA and patients with intramucosal cancer were also included . More patients in the control group developed cancer compared with the treatment group, showing statistical significance; however the numbers were small (one in the treatment group and four in the control group), and hence should be viewed with caution. The incidence of subsquamous intestinal metaplasia or ”buried Barrett’s” was significantly higher in the control group compared with only 5 % in the treated group. Previous reports have shown a much lower incidence of buried Barrett’s in post-RFA patients  compared with the current study, which could be explained by the intensive sampling strategy used here. However, the long-term significance and progression of buried glands remain unknown. The complications in the treatment group included one case of gastrointestinal bleeding, which was managed endoscopically, and two cases of chest pain that required hospital admission. No cases of perforation or death were reported, confirming the safety of this procedure.
Newer modalities of ablation, such as cryotherapy, are emerging, and comparative clinical studies are necessary to find the ideal ablative technique. Also, the role of ablating nondysplastic Barrett’s remains controversial, given that the rate of per-patient year progression to dysplasia or cancer is less than 1 %. However, patients with LGD have a significantly higher risk of progression, particularly when there is a consensus diagnosis by pathologists , and in these situations RFA could be considered. Results from the ongoing European multicenter randomized trial for LGD, which compares surveillance with RFA (SURF study), will be invaluable. In cases of HGD, RFA appears to be the safest and an effective tool for short- to medium-term eradication of dysplasia, with promising results in preventing progression to cancer. Most of the patients included in this trial had ”flat dysplasia,” and in our experience, lesions of ”nodular dysplasia” behave more aggressively. The ongoing EURO II trial, which combines EMR for mucosal lesions followed by RFA, will throw light onto this. The question of buried Barrett’s glands remains a concern; however results with RFA seem better than the reported incidence with other modalities, such as photodynamic therapy (PDT) and argon plasma coagulation (APC).