Radiofrequency ablation of Barrett's esophagus: let's not get ahead of ourselves

Radiofrequency ablation (RFA) represents an exciting advance for the treatment of Barrett’s esophagus. The research work on RFA performed to date has involved a stepwise progression from initial animal studies to human studies prior to esophagectomy, human dosimetry studies, single-center studies, multicenter nonrandomized studies, and ultimately multicenter, randomized, controlled trials [1–5]. This process also led to modifications in the RFA technique and to the development of the focal ablation device. Regardless of the eventual role of RFA, this series of studies illustrates the appropriate steps in the development and application of future ablative technologies. However, this approach may be limited to certain subsets of patients by the high costs required for the development and widespread application of new endoscopic therapeutic technologies. Nevertheless, the impact of this development paradigm in the evolution of RFA is obvious, and both the investigators and the manufacturer of the RFA device are to be congratulated on their achievements. However, in a special article in this issue of Digestive Diseases and Sciences, Fleischer and colleagues [6] make an impassioned plea for the widespread application of RFA to all patients with Barrett’s esophagus regardless of the grade of dysplasia that is premature based on the available data. Let’s take a careful look at the facts, with an emphasis on the application of RFA in patients with nondysplastic Barrett’s esophagus. There is universal agreement that high-grade dysplasia poses a major risk for the development of cancer, and current practice guidelines recommend intervention in these patients [7]. Studies to date, including the landmark randomized controlled trial of Shaheen et al. (ablation of intestinal metaplasia [AIM] dysplasia trial), demonstrate a clear benefit for RFA in the treatment of high-grade dysplasia, ideally with endoscopic mucosal resection of any mucosal abnormalities prior to application [5, 8]. In addition, preliminary results of a randomized controlled clinical trial of circumferential endoscopic mucosal resection versus focal endoscopic mucosal resection plus RFA for highgrade dysplasia and early adenocarcinoma suggest that the two techniques are comparable for the important endpoints of elimination of neoplasia and intestinal neoplasia, but the complication rate for endoscopic mucosal resection plus RFA is substantially lower [9]. Thus, RFA represents a clear advance for the management of patients with highgrade dysplasia. It is important to recognize, however, that a small subset of these patients may still progress onto cancer (2% in the AIM dysplasia trial), and histologic confirmation of complete ablation is never possible with RFA. Low-grade dysplasia has many more nuances, including a natural history that is poorly understood. In addition, the diagnosis is often elusive and not confirmed with repeat endoscopy and biopsies [10, 11]. In part, this may be due to the high degree of interobserver variability in establishing the diagnosis of low-grade dysplasia, and the variable biopsy sampling protocols by which these patients are followed. While the majority of patients with low-grade dysplasia do not progress to high-grade dysplasia or adenocarcinoma, a subset of these patients do progress to a higher-grade lesions. Recent studies suggest an intermediate risk of progression to cancer, with a weighted average G. W. Falk (&) Hospital of the University of Pennsylvania, Division of Gastroenterology, University of Pennsylvania School of Medicine, 3 Ravdin, 3400 Spruce Street, Philadelphia, PA 19104, USA e-mail: gary.falk@uphs.upenn.edu