The Case for Endoscopic Treatment of Non-dysplastic and Low-Grade Dysplastic Barrett’s Esophagus

Abstract

Non-dysplastic mucosa (ND-) in Barrett's esophagus (BE) shows clonal molecular aberrations, loss of cell cycle control, and other features of "neoplasia." These changes occur prior to morphologic expression of neoplasia (dysplasia). Morphologic evaluation of dysplasia is fraught with error, and, as a result, often leads to false-negative and false-positive diagnoses. Early "crypt dysplasia" is difficult to detect, and is often missed in routine biopsy specimens. Some studies show substantial progression rates of low-grade dysplasia (LGD), and crypt dysplasia, to esophageal adenocarcinoma (EAC). Dysplasia, even when fully developed, may, in certain circumstances, be difficult to differentiate from non-dysplastic (regenerating) BE. Radiofrequency ablation (RFA) is a safe and effective method for removing mucosa at risk of cancer. Given the difficulties of dysplasia assessment in mucosal biopsies, and the molecular characteristics of ND-BE, this technique should be considered for treatment of all BE patients, including those with ND or LGD. Post-ablation neo-squamous epithelium reveals no molecular abnormalities, and is biologically stable. Given that prospective randomized controlled trials of ablative therapy for ND-BE aiming at reducing EAC incidence and mortality are unlikely to be completed in the near future, endoscopic ablation is a valid management option. The success of RFA in achieving safe, uniform, reliable, and predictable elimination of BE allows surgeons to combine fundoplication with RFA. Currently, there is no type of treatment for dysplastic or non-dysplastic BE that achieves a complete response in 100% of patients, eliminates all risk of developing cancer, results in zero adverse events, is less expensive in terms of absolute costs than surveillance, is durable for 20+ years, or eliminates the need for surveillance. Regardless, RFA shows established safety, efficacy, durability, and cost-effective profiles that should be considered in the management of patients with non-dysplastic or low-grade dysplastic BE.

Radiofrequency Ablation of Barrett’s Esophagus: Let’s Not Get Ahead of Ourselves

“…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.…”

“…In fact, I would make the case that RFA of nondysplastic Barrett's esophagus is akin to performing plastic surgery on the esophagus; we can make it look pretty, but does RFA really change anything for the patient? Since Fleischer et al [6] tout RFA as a cancer-prevention method, I would like to use the endpoint of development of cancer to make the case that RFA in nondysplastic Barrett's esophagus is not ready for ''prime time'' for a number of reasons.…”

Management of Barrett’s oesophagus and intramucosal oesophageal cancer: a review of recent development

“…Some authorities have suggested that all patients with BO irrespective of the presence of dysplasia should be treated with RFA [Fleischer et al 2010]. This may be related to the availability of endoscopic therapeutic options, the high cost of surveillance and the difficulty in identifying the high-risk progressors to OA.…”

“…The reasons include poor interobserver correlation (reactive changes due to oesophagitis versus LGD), biopsy sampling error and regression of LGD as a result of immunosurveillance [Sharma et al 2004[Sharma et al , 2006bRajendra and Robertson, 2010]. Some authorities have estimated the incidence of OA in LGD to be between 1.7% and 14.6% per annum [Fleischer et al 2010] based on meta-analysis [Wani et al 2009] and individual studies [Skacel et al 2000;Gatenby et al 2009;Lim et al 2007;Veith, 2007]. Nevertheless, in a large multicentre study conducted by one of the authors (PS) revealed that the incidence of OA among patients with Barrett's LGD was even lower at 0.6% per year [Sharma et al 2006b].…”

Diagnosis and management of Barrett’s metaplasia: What’s new

“…A recent meta-analysis demonstrated that ablation significantly reduces the risk for cancer in patients with non-dysplastic BE and LGD [50] . Fleischer et al [51] proposed RFA as a safe, efficient and cost-effective method that should be considered in the management of patients with non-dysplastic or low-grade dysplastic BE, because it achieves complete response in all patients, eliminates all risk of developing cancer, with rare advent effects and less expense than surveillance in terms of absolute costs [51] . These authors reported complete response by intestinal metaplasia in 92% at 5-year follow-up.…”