A microRNA Signature Identifies Patients at Risk of Barrett Esophagus Progression to Dysplasia and Cancer.

BACKGROUND: Progression of Barrett esophagus (BE) to esophageal adenocarcinoma occurs among a minority of BE patients. To date, BE behavior cannot be predicted on the basis of histologic features. AIMS: We compared BE samples that did not develop dysplasia or carcinoma upon follow-up of ≥ 7 years (BE nonprogressed [BEN]) with BE samples that developed carcinoma upon follow-up of 3 to 4 years (BE progressed [BEP]). METHODS: The NanoString nCounter miRNA assay was used to profile 24 biopsy samples of BE, including 13 BENs and 11 BEPs. Fifteen samples were randomly selected for miRNA prediction model training; nine were randomly selected for miRNA validation. RESULTS: Unpaired t tests with Welch's correction were performed on 800 measured miRNAs to identify the most differentially expressed miRNAs for cases of BEN and BEP. The top 12 miRNAs (P < .003) were selected for principal component analyses: miR-1278, miR-1301, miR-1304-5p, miR-517b-3p, miR-584-5p, miR-599, miR-103a-3p, miR-1197, miR-1256, miR-509-3-5p, miR-544b, miR-802. The 12-miRNA signature was first self-validated on the training dataset, resulting in 7 out of the 7 BEP samples being classified as BEP (100% sensitivity) and 7 out of the 8 BEN samples being classified as BEN (87.5% specificity). Upon validation, 4 out of the 4 BEP samples were classified as BEP (100% sensitivity) and 4 out of the 5 BEN samples were classified as BEN (80% specificity). Twenty-four samples were evaluated, and 22 cases were correctly classified. Overall accuracy was 91.67%. CONCLUSION: Using miRNA profiling, we have identified a 12-miRNA signature able to reliably differentiate cases of BEN from BEP.

Multifocal Cryoballoon Ablation for Eradication of Barrett's Esophagus-Related Neoplasia: A Prospective Multicenter Clinical Trial.

INTRODUCTION: Ablation of Barrett's esophagus (BE) is the preferred approach for the treatment of neoplasia without visible lesions. Limited data on cryoballoon ablation (CBA) suggest its potential clinical utility. We evaluated the safety and efficacy of CBA in a multicenter study of patients with neoplastic BE. METHODS: In a prospective clinical trial, 11 academic and community centers recruited consecutive patients with BE of 1-6 cm length and low-grade dysplasia, high-grade dysplasia (HGD), or intramucosal adenocarcinoma (ImCA) confirmed by central pathology. Patients with symptomatic pre-existing strictures or visible BE lesions had dilation or endoscopic mucosal resection (EMR), respectively, before enrollment. A nitrous oxide cryoballoon focal ablation system was used to treat all visible columnar mucosa in up to 5 sessions. Study end points included complete eradication of all dysplasia (CE-D) and intestinal metaplasia (CE-IM) at 1 year. RESULTS: One hundred twenty patients with BE with ImCA (20%), HGD (56%), or low-grade dysplasia (23%) were enrolled. In the intention-to-treat analysis, the CE-D and CE-IM rates were 76% and 72%, respectively. In the per-protocol analysis (94 patients), the CE-D and CE-IM rates were 97% and 91%, respectively. Postablation pain was mild and short lived. Fifteen subjects (12.5%) developed strictures requiring dilation. One patient (0.8%) with HGD progressed to ImCA, which was successfully treated with EMR. Another patient (0.8%) developed gastrointestinal bleeding associated with clopidogrel use. One patient (0.8%) had buried BE with HGD in 1 biopsy, not confirmed by subsequent EMR. DISCUSSION: In patients with neoplastic BE, CBA was safe and effective. Head-to-head comparisons between CBA and other ablation modalities are warranted (clinicaltrials.gov registration NCT02514525).

Clinical utility of wide-area transepithelial sampling with three-dimensional computer-assisted analysis (WATS3D) in identifying Barrett's esophagus and associated neoplasia.

Sampling error during screening and surveillance endoscopy is a well-recognized problem. Wide-area transepithelial sampling with three-dimensional computer-assisted analysis (WATS3D), used adjunctively to forceps biopsy (FB), has been shown to increase the detection of Barrett's esophagus (BE) and BE-associated neoplasia. We evaluated the clinical utility of WATS3D and its impact on the management of patients with BE and dysplasia. Between 2013 and 2018, 432 consecutive patients who had a WATS3D positive and an accompanying FB negative result were identified. Physicians were contacted to determine if the WATS3D result impacted their decision to enroll patients in surveillance or increase the frequency of surveillance, recommend ablation, and/or initiate or increase the dose of proton pump inhibitors (PPIs). WATS3D directly impacted the management of 97.8% of 317 BE patients; 96.2% were enrolled in surveillance and 60.2% were started on PPIs or their dose was increased. WATS3D impacted the management of 94.9% and 94.1% of the 98 low-grade dysplasia and 17 high-grade dysplasia patients, respectively. As a result of WATS3D, 33.7% of low-grade dysplasia and 70.6% of high-grade dysplasia patients underwent endoscopic therapy. More than 37% of all dysplasia patients were enrolled in a surveillance program, and nearly 30% were scheduled to be surveilled more frequently. PPIs were either initiated, or the dose was increased in more than 54% of all dysplasia patients. We demonstrate that WATS3D has high clinical utility. By prompting physicians to change their clinical management in patients with negative FB results, WATS3D, used adjunctively to FB, directly impacts patient management, and improves patient outcomes.

CDX-2 Expression in Esophageal Biopsies Without Goblet Cell Intestinal Metaplasia May Be Predictive of Barrett's Esophagus.

BACKGROUND: CDX-2 is a nuclear homeobox transcription factor not normally expressed in esophageal and gastric epithelia, reported to highlight intestinal metaplasia (IM) in the esophagus. Pathological absence of goblet cells at initial screening via hematoxylin and eosin (HE) and alcian blue (AB) staining results in patient exclusion from surveillance programs. AIMS: This study aimed to determine whether non-goblet cell IM, as defined by CDX-2 positivity, can be considered to be a precursor to Barrett's esophagus (BE). METHODS: This study received IRB approval (17,284). Patients with gastroesophageal reflux disease (n = 181) who underwent upper-gastrointestinal endoscopy with biopsies of the distal esophagus to rule out BE using HE/AB staining and CDX-2 immunostaining were followed for 3 years. Initial and follow-up staining results were evaluated for age/sex. RESULTS: Differences between development of goblet cell IM in CDX-2-negative and CDX-2-positive groups were evaluated. A Kaplan-Meier curve showed that, out of the 134 patients initially positive for CDX-2, 25 (18.7%) had developed goblet cell IM after 2 years and 106 (79.1%) after 3 years. Conversely, of the 47 patients initially negative for CDX-2, 8 (17.9%) developed goblet cell IM after 24 months and only 11 (23.8%) after 40 to 45 months (P = .049; age-adjusted Cox proportional hazard regression model). CONCLUSION: In cases that are initially AB negative and CDX-2 positive, CDX-2 was demonstrated to have a potential prognostic utility for early detection of progression to BE. CDX-2 expression is significantly predictive for risk of goblet cell IM development 40 to 45 months after initial biopsy.

Incidence of Esophageal Adenocarcinoma and Causes of Mortality After Radiofrequency Ablation of Barrett's Esophagus.

BACKGROUND & AIMS: Radiofrequency ablation (RFA) is commonly used to treat Barrett's esophagus (BE). We assessed the incidence of esophageal adenocarcinoma (EAC) after RFA, factors associated with the development of EAC, and EAC-specific and all-cause mortality. METHODS: We collected data for outcomes of patients who underwent RFA for BE from July 2007 through July 2011 from US multicenter RFA Patient Registry. Patients were followed until July 2014. Kaplan-Meier curves of EAC incidence were stratified by baseline histology. Crude EAC incidence and mortality (all-cause and EAC-specific) were calculated, and adjusted all-cause mortality was assessed. Logistic regression models were constructed to assess predictors of EAC and all-cause mortality. RESULTS: Among 4982 patients, 100 (2%) developed EAC (7.8/1000 person-years [PY]) and 9 patients (0.2%) died of EAC (0.7/1000 PY) in a mean 2.7 ± 1.6 years. The incidence of EAC in nondysplastic BE was 0.5/1000 PY. Overall, 157 patients (3%) died during follow-up (all-cause mortality, 11.2/1000 PY). On multivariate logistic regression, baseline BE length (odds ratio, 1.1/ cm) and baseline histology (odds ratios, 5.8 and 50.3 for low-grade dysplasia and high-grade dysplasia [HGD] respectively) predicted EAC incidence. Among 9 EAC deaths, 6 (67%) had baseline HGD, and 3 (33%) had baseline intramucosal EAC. The most common causes of death were cardiovascular (15%) and extraesophageal cancers (15%). No deaths were associated with RFA. CONCLUSIONS: Based on analysis of a multicenter registry of patients who underwent RFA of BE, less than 1% died from EAC. The incidence of EAC was markedly lower in this study than in other studies of disease progression, with the greatest absolute benefit observed in patients with HGD.

Treatment of chronic radiation proctopathy with radiofrequency ablation (with video).

BACKGROUND: Chronic radiation proctopathy (CRP) is a common sequela occurring even many years after pelvic radiation. Current ablative therapies for bleeding ectatic vessels have the potential for deep tissue injury leading to ulcerations, perforation, and fistulas. Radiofrequency ablation (RFA) therapy avoids deep tissue injury and is a promising treatment for CRP. OBJECTIVE: To assess the long-term safety and efficacy of RFA for the treatment of CRP. DESIGN: Multicenter, retrospective analysis of a prospectively collected database. SETTING: Veterans Affairs Boston Healthcare System, Massachusetts; Sarasota Memorial Hospital and Suncoast Endoscopy of Sarasota, Florida. PATIENTS: A total of 39 consecutive patients with CRP. INTERVENTIONS: Endoscopic RFA of CRP. MAIN OUTCOME MEASUREMENTS: The primary endpoint of the study was complete resolution of rectal bleeding. Secondary endpoints included visually scored improvement of CRP on endoscopic follow-up by using a rectal telangiectasia density (RTD) grading score, improvement in hemoglobin level, and adverse events related to the procedure. RESULTS: A total of 39 male patients (mean [± standard deviation {SD}] age 72.9 ± 6.6 years) were included in the study. The mean number of RFA sessions was 1.49 (median 1, interquartile range [IQR] 1-2, range 1-4), with a mean interval of 18 weeks between sessions. Rectal bleeding stopped completely in all patients during the mean follow-up of 28 months (range 7-53 months). A significant improvement occurred in the mean (± SD) hemoglobin level from 11.8 ± 2 to 13.5 ± 1.6 g % (P < .0001). Endoscopic severity also improved significantly with an improvement in the median RTD score from 3 (IQR 2-3) to 0 (IQR 0-1) (P < .0001). Treatment with RFA led to discontinuation of blood transfusion and iron therapy in 92% and 82% patients, respectively. LIMITATIONS: Retrospective analysis, lack of control group. CONCLUSION: RFA therapy led to complete resolution of rectal bleeding in all treated CRP patients, with improvement in clinical and endoscopic indices without any major adverse events. Further controlled studies are needed to establish RFA as the endoscopic therapy of choice for treatment of CRP.

Prior fundoplication does not improve safety or efficacy outcomes of radiofrequency ablation: results from the U.S. RFA Registry.

BACKGROUND: Ongoing gastroesophageal reflux may impair healing and re-epithelialization after radiofrequency ablation (RFA) of Barrett's esophagus (BE). Because prior fundoplication may improve reflux control, our aim was to assess the relationship between prior fundoplication and the safety/efficacy of RFA. METHODS: We assessed the U.S. RFA Registry, a nationwide registry of BE patients receiving RFA at 148 institutions, to compare the safety and efficacy of ablation between those with prior fundoplication and those with medical management (proton pump inhibition). RESULTS: Among 5,537 patients receiving RFA, 301 (5.4 %) had prior fundoplication. Of fundoplication subjects, 1.0 % developed stricture and 1.0 % were hospitalized after RFA. Rates of stricture, bleeding, and hospitalization were not statistically different (p = ns) between patients with and without prior fundoplication. Complete eradication of intestinal metaplasia and complete eradication of dysplasia were achieved in 71 % and 87 % of fundoplication patients, and 73 % and 87 % of patients without fundoplication, respectively (p = ns for both). Patients with prior fundoplication needed similar numbers of RFA sessions for eradication compared with those without fundoplication. CONCLUSIONS: Radiofrequency ablation, with or without prior fundoplication, is safe and effective in eradicating BE. Prior fundoplication was associated with similar adverse event and efficacy rates when compared with medical management.