Radiofrequency Ablation (RFA)
One randomized trial using RFA in Barrett’s esophagus with dysplasia has been published. A randomized, multicenter, sham-controlled trial assigned 127 patients with dysplastic Barrett’s esophagus in a 2:1 ratio to receive RFA or a sham procedure. The groups were randomized according to the grade of dysplasia (low-grade [n=64] or high-grade [n=63]) and length of the Barrett’s esophagus (<4 cm or 4-8 cm). Primary outcomes were the proportion of patients with low-grade or high-grade dysplasia who had complete eradication of dysplasia at 12 months and the proportion of all patients who had complete eradication of intestinal metaplasia at 12 months. Secondary outcomes included the proportion of patients who had progression of dysplasia, including low to high-grade dysplasia or to cancer, and the progression of high-grade dysplasia to cancer. Among patients in the RFA group, the entire segment of Barrett’s esophagus was ablated. Patients in the RFA group could receive up to 4 ablation sessions, performed at baseline, and at 2, 4, and 9 months. In patients with low-grade dysplasia, the dysplasia was completely eradicated in 90.5% of those in the RFA group, compared with 22.7% of those in the control group (p<0.001). In patients with high-grade dysplasia, complete eradication occurred in 81% of the ablation group versus 19% in the control group (p<0.001). Overall, complete eradication of intestinal metaplasia was 77.4% in the ablation group compared with 2.3% of the control group (p<0.001) Patients who did not receive RFA were more likely to have disease progression (16.3%) than those that received RFA (3.6%; p=0.03). Among patients with high-grade dysplasia, 19% of those in the control group progressed to cancer, versus 2.4% progression to cancer in the RFA group (p=0.04). Three serious adverse events occurred in the RFA group, including one episode of upper gastrointestinal hemorrhage, which was treated endoscopically, one overnight hospitalization for new-onset chest pain 8 days after RFA and one night of hospitalization for an episode of chest discomfort and nausea immediately after RFA. No adverse events were observed in the control group. No esophageal perforations or procedure-related deaths occurred. Among patients in the RFA group, esophageal stricture developed in five patients (6%), all of which were successfully dilated endoscopically. To date, the remainder of the studies using RFA for Barrett’s esophagus have been conducted to investigate the safety and efficacy of this technique, and have consisted mainly of small numbers of patients with relatively short follow-up.
Ganz et al. reported registry data from 142 patients with Barrett’s esophagus who underwent circumferential ablation for high-grade dysplasia. The patients were from 16 academic and community centers, treated between 2004 and 2007, and ranged in age from 59–75 years (median age, 66 years). Median length of Barrett’s esophagus segment was 6 cm (range, 3–8 cm). No adverse events were reported. Ninety-two of the patients had at least one follow-up biopsy (median follow-up: 12 months; range: 8–15 months). Outcome measures were defined as histologic complete response (CR), defined as all biopsy specimens negative for high-grade dysplasia, any dysplasia, or intestinal metaplasia. CR was achieved for high-grade dysplasia in 90.2%, any dysplasia in 80.4%, and intestinal metaplasia in 54.3%.
Sharma et al. reported their experience with 100 patients with Barrett’s esophagus without dysplasia, to investigate the safety and efficacy of balloon-based circumferential radiofrequency ablation. Patient age ranged from 18–75 years (median: 55.7 years). This prospective study involved 8 U.S. centers, between 2003 and 2005. Sixty-nine of 70 patients who underwent mucosal ablation were available for follow-up. Efficacy was evaluated with follow-up endoscopy and biopsy at 1, 3, 6, and 12 months. If patients had Barrett’s esophagus present at month 1 or 3, repeat ablation was performed. CR was defined as all biopsy specimens negative for Barrett’s esophagus at 12 months and was achieved in 70% of patients. The authors reported an extension of this trial, evaluating 62 of the original patients, 61 of which were available for 30-month follow-up. Fifty-nine of the 62 patients had to undergo additional focal ablation after the 12-month follow-up. CR was achieved in 60 (98%) of the patients at the end of the 30 months.
Pouw et al. reported their experience with 44 patients with Barrett’s esophagus less than 12 cm in length with either high-grade dysplasia or early carcinoma. Prior to ablation, visible lesions and early carcinoma were endoscopically removed. After ablation, complete histological eradication of all dysplasia and intestinal metaplasia was achieved in 43 patients (98%). No dysplasia had recurred after 21 months of follow-up (range: 10–27 months).
Roorda et al. reported their experience using radiofrequency ablation in 13 patients with Barrett’s esophagus (three with high-grade dysplasia, four with low-grade dysplasia, and six with nondysplastic intestinal metaplasia). Mean baseline Barrett’s esophagus length was 6 cm (range: 2–12 cm). Complete eradication of Barrett’s esophagus was achieved in 6 of 13 patients (46%). Complete elimination of dysplasia was achieved in five of seven (71%) patients.
Hernandez et al. reported on a pilot series in 10 patients with Barrett’s esophagus, followed up for at least 12 months. Seven patients had Barrett’s esophagus without dysplasia, two with low-grade dysplasia, and one with high-grade dysplasia. Complete eradication of Barrett’s esophagus was achieved in seven patients and partial eradication in three.
Reports of the efficacy of the HALO system in ablating Barrett’s esophagus have been as high as 70% (comparable to alternative methods of ablation [e.g., APC and MPEC]), and even higher in some reports. The incidence of leaving behind “buried” foci of intestinal metaplasia has been reported to be 20–44% with APC and 7% with MPEC; reports using the HALO system have been 0%. Another potential advantage to the HALO system is that because it is automated, it eliminates operator-dependent error that may be seen with APC and MPEC.
Published efficacy data for cryoablation in Barrett’s esophagus are limited. Johnston and colleagues conducted a prospective, single-center pilot study in 11 men with Barrett’s esophagus and degrees of dysplasia ranging from none to multifocal high-grade dysplasia. The mean length of Barrett’s was 4.6 cm (range: 1–8 cm). After six months’ follow-up, complete histologic eradication of Barrett’s esophagus was achieved in seven of the nine patients (78%) completing the protocol. An open-label, single-center, prospective, nonrandomized cohort study assessed the safety of cryoablation as a treatment option for Barrett’s esophagus with high-grade dysplasia or early cancer (intramucosal carcinoma). Thirty patients who were either deemed high-risk surgical candidates or who refused esophagectomy underwent cryoablation. Twenty-seven patients (90%) had downgrading of pathology stage after treatment. After a median follow-up period of 12 months, elimination of cancer or downgrading of high-grade dysplasia was 68% for high-grade dysplasia and 80% for intramucosal cancer.
American College of Gastroenterology
According to guidelines from the American College of Gastroenterology, “…high-grade dysplasia is associated with a 30% risk of cancer development. Treatment needs to be individualized with options of careful intensive surveillance, endoscopic ablation therapy, and surgical resection being presented to the patient based on their appropriateness for these options and the expertise available to provide them. At the current time, it appears as if surveillance with intensive biopsies, endoscopic ablative techniques (most likely a combination of techniques), or esophagectomy may produce similar outcomes in retrospective cohort studies from expert centers. The selection of which of these therapies must be individualized and will depend on the expertise available in the patient’s community, the patient’s preferences, and the gastroenterologist’s own experience (Grade B recommendation)”.
The Society of Thoracic Surgeons Practice Guideline Series: Guidelines for the Management of Barrett’s Esophagus with High-Grade Dysplasi
The 2009 guidelines for the management of Barrett’s esophagus, note that RFA may be considered to treat patients with Barrett’s metaplasia, and that it may be effective for ablation of high-grade dysplasia, but that further trials are needed before this can be recommended in preference to currently available ablative therapies. Specific to pathologist interpretation of high-grade dysplasia the guidelines note the following as a Class I Recommendation, “Histological evaluation of high-grade dysplasia should be undertaken by two pathologists experienced in interpreting esophageal metaplasia.
National Comprehensive Cancer Network Guidelines
The 2010 National Comprehensive Cancer Network clinical practice guidelines for esophageal cancer state that esophageal cancer stage Tis (carcinoma in situ) or T1a (intramucosal invasion) may be treated primarily with endoscopic mucosal resection, esophagectomy, or ablation; RAF is not specifically addressed and the guidelines state that among the methods of mucosal ablation, photodynamic therapy is superior for achieving ablation of metaplastic and dysplastic epithelium as well as for obviating the need for further interventions.
2009 National Cancer Institute
The 2009 Clinical Trials Database (PDQ®) of the U.S. National Institutes of Health ClinicalTrials.gov registry identified a phase II/III trial currently recruiting participants with Barrett’s esophagus and gastroesophageal reflux disease. The aim of the study is to evaluate the long-term efficacy of evidence-based diagnostic and therapeutic algorithms and techniques (such as radiofrequency). Estimated enrollment is 100 patients, with an estimated study completion date of August 2017 (NCT00513331).
A search of peer reviewed literature was conducted through February 2010. Radiofrequency ablation of high-grade dysplasia in Barrett’s esophagus has been shown to be at least as effective in eradicating high-grade dysplasia as other ablative techniques with a lower progression rate to cancer, and may be considered as an alternative to esophagectomy. More data are required concerning the use of RFA for the eradication of low-grade dysplasia and nondysplastic Barrett’s esophagus. Longer follow-up is needed to show that eradication will persist, and that the benefits will outweigh potential complications in these patients who show a lower rate of progression to adenocarcinoma than those with high-grade dysplasia. Data for the efficacy of cryoablation of Barrett’s esophagus with or without dysplasia are limited. The studies consist of small numbers of patients with short-term follow-up.
RFA for Low-Grade Dysplasia
Review of literature through October 2011 identified a 2011 Position Statement from the American Gastroenterological Association (AGA) addressing the management of Barrett’s esophagus. Specific to low-grade dysplasia, the AGA recommends that RFA should be considered a therapeutic option for treatment of patients with confirmed low-grade dysplasia in Barrett’s esophagus. In addition the AGA notes “RFA therapy for patients with low-grade dysplasia lead to reversion to normal-appearing squamous epithelium in >90% of cases with quality of evidence documented as high.
Shaheen et al. performed a follow-up of the subjects from the AIM Dysplasia trial to an average of 3.05 years. The authors note that this study demonstrated that a high percentage of subjects with both low-grade and high-grade dysplasia retain complete eradication of dysplasia and intestinal metaplasia after treatment. Progression of disease was rare in subjects who underwent RFA treatment, and the rate of progression to EAC in this dysplastic cohort was 0.55%. There was no procedure- or cancer-related mortality. The main adverse side effect was stricture occurrence, which occurred in 7.6% of subjects and correctable with dilation.
RFA and Cryoablation for Nondysplasia (without dysplasia)
The 2011 AGA Position Statement notes there is no data from controlled trials showing that endoscopic eradication therapy, including RFA and cryotherapy, is more effective at reducing cancer risk or more cost-effective than long-term endoscopic surveillance in patients with Barrett’s esophagus in the absence of dysplasia. Quality of evidence for this documentation indication is documented as low.
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