The role of endoscopic submucosal dissection (ESD) in the treatment of Barrett esophagus-associated neoplasia (BEN) has been evolving. We examined the efficacy and safety of ESD and endoscopic mucosal resection (EMR) for BEN.

A database search was performed for studies reporting efficacy and safety outcomes of ESD and EMR for BEN. Pooled proportional and comparative meta-analyses were performed.

47 studies (23 ESD, 19 EMR, 5 comparative) were included. The mean lesion sizes for ESD and EMR were 22.5 mm and 15.8 mm, respectively; most lesions were Paris type IIa. For ESD, pooled analysis showed rates of en bloc, R0, and curative resection, and local recurrence of 98%, 78%, 65%, and 2%, respectively. Complete eradication of dysplasia and intestinal metaplasia were achieved in 94% and 59% of cases, respectively. Pooled rates of perforation, intraprocedural bleeding, delayed bleeding, and stricture were 1%, 1%, 2%, and 10%, respectively. For EMR, pooled analysis showed rates of en bloc, R0, and curative resection, and local recurrence of 37%, 67%, 62%, and 6%, respectively. Complete eradication of dysplasia and intestinal metaplasia were achieved in 94% and 75% of cases. Pooled rates of perforation, intraprocedural bleeding, delayed bleeding, and stricture were 0.1%, 1%, 0.4%, and 8%, respectively. The mean procedure times for ESD and EMR were 113 and 22 minutes, respectively. Comparative analysis showed higher en bloc and R0 resection rates with ESD compared with EMR, with comparable adverse events.

ESD and EMR can both be employed to treat BEN depending on lesion type and size, and center expertise.

Endoscopic eradication therapy (EET) is recommended for patients with Barrett's esophagus (BE)-associated neoplasia and is effective in achieving complete eradication of intestinal metaplasia (CE-IM). However, BE that is refractory to EET, defined as partial or no improvement in dysplasia after less than or equal to 3 ablative sessions, and the development of recurrence post-EET is not uncommon. Identification of refractory BE or recurrent intestinal metaplasia should prompt esophageal physiologic testing and modification of antireflux strategy, as appropriate. In patients who ultimately fail standard EET despite optimization of reflux control, salvage EET with alternate modalities may need to be considered.

The progression of Barrett's esophagus (BE) to early esophageal carcinoma occurs sequentially; the metaplastic epithelium develops from a low-grade dysplasia to a high-grade dysplasia (HGD), resulting in early esophageal carcinoma and, eventually, invasive carcinoma. Endoscopic approaches including resection and ablation can be used in the treatment of this condition.

To compare the effectiveness of radiofrequency ablation (RFA) vs endoscopic mucosal resection (EMR) + RFA in the endoscopic treatment of HGD and intramucosal carcinoma.

In accordance with PRISMA guidelines, this systematic review included studies comparing the two endoscopic techniques (EMR + RFA and RFA alone) in the treatment of HGD and intramucosal carcinoma in patients with BE. Our analysis included studies involving adult patients of any age with BE with HGD or intramucosal carcinoma. The studies compared RFA and EMR + RFA methods were included regardless of randomization status.

The seven studies included in this review represent a total of 1950 patients, with 742 in the EMR + RFA group and 1208 in the RFA alone group. The use of EMR + RFA was significantly more effective in the treatment of HGD [RD 0.35 (0.15, 0.56)] than was the use of RFA alone. The evaluated complications (stenosis, bleeding, and thoracic pain) were not significantly different between the two groups.

Endoscopic resection in combination with RFA is a safe and effective method in the treatment of HGD and intramucosal carcinoma, with higher rates of remission and no significant differences in complication rates when compared to the use of RFA alone.

Endoscopic cryotherapy can eradicate neoplastic Barrett's esophagus (BE). A new contact cryoballoon focal ablation system (CbFAS)) freezes esophageal mucosa with nitrous oxide. We studied the safety and efficacy of CbFAS for complete eradication of neoplastic Barrett's esophagus.

In a prospective clinical trial, consecutive BE patients with confirmed neoplasia (low-grade dysplasia [LGD], high-grade dysplasia [HGD], and/or intramucosal adenocarcinoma [ImCA]), at least 1 cm of BE, with or without prior ablation, were treated with a dose 10 seconds of spray per site. EMR was performed for nodular lesions. Treatments were repeated every 10 to 12 weeks until complete eradication, with a maximum of 5 treatments. Primary outcomes were complete eradication of all dysplasia (CE-D) and complete eradication of intestinal metaplasia (CE-IM) at 1 year (intention-to-treat analysis).

Forty-one assessable patients (22 treatment naive, 19 previously ablated) with LGD (n = 13), HGD (n = 23), or ImCA (n = 5) were treated. The median procedure time was 30 minutes. The median number of ablation procedures for CE-IM was 3 (interquartile range, 2-4). Overall 1-year CE-D and CE-IM rates were 95% and 88%, respectively. CE-D rate was significantly lower (67%) in those with ultra-long BE compared with those with <8 cm (100%, P = .02). Median pain scores were zero at day 1. Four patients (9.7%) developed mild dysphagia from stenoses requiring dilation. One patient on aspirin developed upper GI bleeding that did not require therapy.

Multifocal nitrous oxide cryotherapy using CbFAS is a promising, highly effective, and safe endoscopic treatment for primary or rescue therapy of BE-associated neoplasia and IM. (Clinical trial registration number: NCT02534233.).

Endoscopic eradication therapy is effective and durable for the treatment of Barrett's esophagus (BE), with low rates of recurrence of dysplasia but significant rates of recurrence of intestinal metaplasia. Identified risk factors for recurrence include age and length of BE before treatment and may also include presence of a large hiatal hernia, higher grade of dysplasia before treatment, and history of smoking. Current guidelines for surveillance following ablation are limited, with recommendations based on low-quality evidence and expert opinion. New modalities including optical coherence tomography and wide-area tissue sampling with computer-assisted analysis show promise as adjunctive surveillance modalities.

 Conflicting data exist with regard to recurrence rates of intestinal metaplasia (IM) and dysplasia after achieving complete eradication of intestinal metaplasia (CE-IM) in Barrett's esophagus (BE) patients.

 (i) To determine the incidence of recurrent IM and dysplasia achieving CE-IM and (ii) to compare recurrence rates between treatment modalities [radiofrequency ablation (RFA) with or without endoscopic mucosal resection (EMR) vs stepwise complete EMR (SRER)].

 A systematic search was performed for studies reporting on outcomes and estimates of recurrence rates after achieving CE-IM. Pooled incidence [per 100-patient-years (PY)] and risk ratios with 95 %CI were obtained. Heterogeneity was measured using the I² statistic. Subgroup analyses, decided a priori, were performed to explore heterogeneity in results.

 A total of 39 studies were identified (25-RFA, 13-SRER, and 2 combined). The pooled incidence of any recurrence was 7.5 (95 %CI 6.1 - 9.0)/100 PY with a pooled incidence of IM recurrence rate of 4.8 (95 %CI 3.8 - 5.9)/100 PY, and dysplasia recurrence rate of 2.0 (95 %CI 1.5 - 2.5)/100 PY. Compared to the SRER group, the RFA group had significantly higher overall [8.6 (6.7 - 10.5)/100 PY vs. 5.1 (3.1 - 7)/100 PY, P  = 0.01] and IM recurrence rates [5.8 (4.3 - 7.3)/100 PY vs. 3.1 (1.7 - 4)/100 PY, P  < 0.01] with no difference in recurrence rates of dysplasia. Significant heterogeneity between studies was identified. The majority of recurrences were amenable to repeat endoscopic eradication therapy (EET).

 The results of this study demonstrate that the incidence rates of overall, IM, and dysplasia recurrence rates post-EET are not inconsiderable and reinforce the importance of close surveillance after achieving CE-IM.

Recent data suggest that effective control of gastroesophageal reflux improves outcomes associated with endoscopic eradication therapy (EET) for Barrett's esophagus (BE). However, the impact of reflux control on preventing recurrent intestinal metaplasia and/or dysplasia is unclear. The aims of the study were: (a) to determine the effectiveness and durability of EET under a structured reflux management protocol and (b) to determine the impact of optimizing anti-reflux therapy on achieving complete eradication of intestinal metaplasia (CE-IM).

Consecutive BE patients referred for EET were enrolled and managed with a standardized reflux management protocol including twice-daily PPI therapy during eradication. Primary outcomes were rates of CE-IM and IM or dysplasia recurrence.

Out of 221 patients enrolled (46.0% with high-grade dysplasia/intramucosal carcinoma, 34.0% with low-grade dysplasia, and 20.0% with non-dysplastic BE) an overall CE-IM of 93% was achieved within 11.6±10.2 months. Forty-eight patients did not achieve CE-IM in 3 sessions. After modification of their reflux management, 45 (93.7%) achieved CE-IM in a mean of 1.1 RFA sessions. Recurrence occurred in 13 patients (IM in 10(4.8%), dysplasia in 3 (1.5%)) during a mean follow-up of 44±18.5 months. The only significant predictor of recurrence was the presence of a hiatal hernia. Recurrence of IM was significantly lower than historical controls (10.9 vs. 4.8%, P=0.04).

The current study highlights the importance of reflux control in patients with BE undergoing EET. In this setting, EET has long-term durability with low recurrence rates providing early evidence for extending endoscopic surveillance intervals after EET.

Focal EMR followed by radiofrequency ablation (f-EMR + RFA) and stepwise or complete EMR (s-EMR) are established strategies for eradication of Barrett's esophagus (BE)-related high-grade dysplasia (HGD) and/or esophageal adenocarcinoma (EAC)/intramucosal carcinoma (IMC). The objective of this study was to derive pooled rates of efficacy and safety of individual methods in a large cohort of patients with BE and to indirectly compare the 2 methods.

PubMed, Embase, Web of Science, Cochrane, and major conference proceedings were searched. A systematic review and pooled analysis were carried out to determine the following outcomes in patients with BE undergoing either f-EMR + RFA or s-EMR: (1) complete eradication rates of neoplasia (CE-N) and intestinal metaplasia (CE-IM); (2) recurrence rates of cancer (EAC), dysplasia, and IM; (3) incidence rates of adverse events. Mixed logistic regression was performed as an exploratory analysis to examine differences in outcomes between the 2 methods.

Nine studies (774 patients) of f-EMR + RFA and 11 studies (751 patients) of s-EMR were included. Patients undergoing f-EMR + RFA had high BE eradication rates (CE-N, 93.4%; CE-IM, 73.1%), whereas strictures occurred in 10.2%, bleeding in 1.1%, and perforations in 0.2% of patients. Recurrence of EAC, dysplasia, and IM was 1.4%, 2.6%, and 16.1%, respectively, in this group. Patients undergoing s-EMR also showed high BE eradication rates (CE-N, 94.9%; CE-IM, 79.6%) but a higher rate of adverse events (strictures in 33.5%, bleeding in 7.5%, and perforation in 1.3%). Recurrence of EAC, dysplasia, and IM was 0.7%, 3.3%, and 12.1%, respectively, in the s-EMR group. Mixed logistic regression showed that patients undergoing s-EMR might be more likely to develop esophageal strictures (odds ratio [OR], 4.73; 95% confidence interval [CI], 1.61-13.85; P = .005), perforation (OR, 7.00; 95% CI, 1.56-31.33; P = .01), and bleeding (OR, 6.88; 95% CI, 2.19-21.62; P = 0.001) compared with f-EMR + RFA.

In patients with HGD/EAC, f-EMR followed by RFA seems to be equally effective as and safer than s-EMR.

Endotherapy in cases of neoplastic Barrett esophagus (BE) relapse after successful initial endoscopic management is commonly accepted, but few studies analyze this topic and also take into account the metachronous lesions.

To evaluate the efficiency of endotherapy in the case of neoplastic BE relapse after successful complete endoscopic eradication of neoplastic BE and metaplastic BE.

Retrospective review of medical records was collected in a computerized and prospective manner between 2000 and 2015, in a single tertiary care center. Recurrence was defined by histological presence of high-grade dysplasia or superficial adenocarcinoma at least 6 months after the end of successful initial endotherapy.

Eighteen patients were assessed (1F/17 M). Delay between initial treatment and relapse was 16.6 months (range 6-33). Endotherapy for relapse obtained a sustained and complete remission for 8/18 (44%) patients, with an average endoscopic follow-up of 28 months. The complication rate of endotherapy was 6%. Surgical management was required in 33% (2 pT2N0M0, 2 pTisN0M0, 1 pTm2N0M0 and 1 pTm3N0M0) and salvage radiochemotherapy in 17% (3/18). One patient treated by 6 sessions of ER was considered as a failure given the multiple sessions of endotherapy. Multivariate analysis showed that length of BE (>5 cm), late stenosis adverse events and the quality of vertical margin during initial ER are predictive factors for disease-free survival (p value < 0.01, Hazard Ratio up to 0.076).

Endotherapy could be a treatment for management of neoplastic BE relapse, but should be carefully used, with strict follow-up.

Radiofrequency ablation (RFA) with or without endoscopic mucosal resection (EMR) is routinely used for treatment of Barrett's esophagus with dysplasia. Despite the relative safety of this method, there have been imprecise estimates of the rate of adverse events. We performed a systematic review and meta-analysis to assess the rate of adverse events associated with RFA with and without EMR.

We searched MEDLINE, Embase, Web of Science, and Cochrane Central through October 22, 2014. The primary outcome of interest was the overall rate of adverse events after RFA with or without EMR. We used forest plots to contrast effect sizes among studies.

Of 1521 articles assessed, 37 met our inclusion criteria (comprising 9200 patients). The pooled rate of all adverse events from RFA with or without EMR was 8.8% (95% confidence interval [CI], 6.5%-11.9%); 5.6% of patients developed strictures (95% CI, 4.2%-7.4%), 1% had bleeding (95% CI, 0.8%-1.3%), and 0.6% developed a perforation (95% CI, 0.4%-0.9%). In studies that compared RFA with vs without EMR, the relative risk for adverse events was significantly higher for RFA with EMR (4.4) (P = .015). There was a trend toward higher proportions of adverse events in prospective studies compared with retrospective studies (11.3% vs 7.8%, P = .20). Other factors associated with adverse events included Barrett's esophagus and length and baseline histology.

In a systematic review and meta-analysis, we found the relative risk for adverse events from RFA to be about 4-fold higher with EMR than without; we identified factors associated with these events. Endoscopists should discuss these risks with patients before endoscopic eradication therapy.

The effects of preceding endoscopic mucosal resection (EMR) on the efficacy and safety of radiofrequency ablation (RFA) for treatment of nodular Barrett's esophagus (BE) is poorly understood. Prior studies have been limited to case series from individual tertiary care centers. We report the results of a large, multicenter registry. We assessed the effects of preceding EMR on the efficacy and safety of RFA for nodular BE with advanced neoplasia (high-grade dysplasia or intramucosal carcinoma) using the US RFA Registry, a nationwide study of BE patients treated with RFA at 148 institutions. Safety outcomes included stricture, gastrointestinal bleeding, and hospitalization. Efficacy outcomes included complete eradication of intestinal metaplasia (CEIM), complete eradication of dysplasia (CED), and number of RFA treatments needed to achieve CEIM. Analyses comparing patients with EMR before RFA to patients undergoing RFA alone were performed with Student's t-test, Chi-square test, logistic regression, and Kaplan-Meier analysis. Four hundred six patients were treated with EMR before RFA for nodular BE, and 857 patients were treated with RFA only for non-nodular BE. The total complication rates were 8.4% in the EMR-before-RFA group and 7.2% in the RFA-only group (P = 0.48). Rates of stricture, bleeding, and hospitalization were not significantly different between patients treated with EMR before RFA and patients treated with RFA alone. CEIM was achieved in 84% of patients treated with EMR before RFA, and 84% of patients treated with RFA only (P = 0.96). CED was achieved in 94% and 92% of patients in EMR-before-RFA and RFA-only group, respectively (P = 0.17). Durability of eradication did not differ between the groups. EMR-before-RFA for nodular BE with advanced neoplasia is effective and safe. The preceding EMR neither diminished the efficacy nor increased complication rate of RFA treatment compared to patients with advanced neoplasia who had RFA with no preceding EMR. Preceding EMR is not associated with poorer outcomes in RFA.

In patients with Barrett's esophagus (BE), radiofrequency ablation (RFA) safely and effectively eradicates dysplasia and intestinal metaplasia. We aimed to determine the efficacy and durability of RFA for patients with dysplastic and nondysplastic BE.

We performed a systematic review and meta-analysis of studies identified in PubMed and EMBASE that reported the proportion of patients treated with RFA who had complete eradication of dysplasia (CE-D) and intestinal metaplasia (CE-IM), and the proportion of patients with recurrent IM after successful treatment. Pooled estimates of CE-D, CE-IM, IM recurrence, and adverse events were calculated.

We identified 18 studies of 3802 patients reporting efficacy and 6 studies of 540 patients reporting durability. Ten were prospective cohort studies, 9 were retrospective cohort studies, and 1 was a randomized trial. CE-IM was achieved in 78% of patients (95% confidence interval [CI], 70%-86%) and CE-D was achieved in 91% (95% CI, 87%-95%). After eradication, IM recurred in 13% (95% CI, 9%-18%). Progression to cancer occurred in 0.2% of patients during treatment and in 0.7% of those after CE-IM. Esophageal stricture was the most common adverse event and was reported in 5% of patients (95% CI, 3%-7%). Confidence in most summary estimates was limited by a high degree of heterogeneity, which did not appear to be caused by single outlier studies.

Treatment of BE with RFA results in CE-D and CE-IM in a high proportion of patients, with few recurrences of IM after treatment and a low rate of adverse events. Despite the large amount of study heterogeneity, these data provide additional information for patients and providers to make informed treatment decisions.

Endoscopic therapy (ablation +/- endoscopic resection) for high-grade dysplasia and/or intramucosal carcinoma (IMC) of the esophagus has demonstrated promising results. However, there is a concern that a curable, local disease may progress to systemic disease with repeated endotherapy. We performed a retrospective review of patients who underwent esophagectomy after endotherapy at three tertiary care esophageal centers from 2006 to 2012. Our objective was to document the clinical and pathologic outcomes of patients who undergo esophagectomy after failed endotherapy. Fifteen patients underwent esophagectomy after a mean of 13 months and 4.1 sessions of endotherapy for progression of disease (53%), failure to clear disease (33%), or recurrence (13%). Initially, all had Barrett's, 73% had ≥3-cm segments, 93% had a nodule or ulcer, and 91% had multifocal disease upon presentation. High-grade dysplasia was present at index endoscopy in 80% and IMC in 33%, and some patients had both. Final pathology at esophagectomy was T0 (13%), T1a (60%), T1b (20%), and T2 (7%). Positive lymph nodes were found in 20%: one patient was T2N1 and two were T1bN1. Patients with T1b, T2, or N1 disease had more IMC on index endoscopy (75% vs. 18%) and more endotherapy sessions (median 6.5 vs. 3). There have been no recurrences a mean of 20 months after esophagectomy. Clinical outcomes were comparable to other series, but submucosal invasion (27%) and node-positive disease (20%) were encountered in some patients who initially presented with a locally curable disease and eventually required esophagectomy after failed endotherapy. An initial pathology of IMC or failure to clear disease after three treatments should raise concern for loco-regional progression and prompt earlier consideration of esophagectomy.

Endoscopic therapy (ablation ± mucosal resection) for esophageal high-grade dysplasia (HGD) or intramucosal carcinoma has demonstrated promising results. Little is known about patients who have persistent or progressive disease despite endotherapy. We compared patients who had successful eradication of their disease with those in whom endotherapy failed to try to identify factors predictive of failure and outcomes after salvage therapy.

We performed a single-institution retrospective review of patients treated with endotherapy from 2007 to 2012.

Thirty-eight patients underwent endotherapy: 28 had successful eradication of their disease and endotherapy failed in 10 patients. Patients in whom endotherapy failed were more likely to have high-grade dysplasia (HGD) on initial endoscopy, nodules or ulcers, multifocal dysplasia, and persistent nondysplastic Barrett's metaplasia. Patients in whom endotherapy failed also underwent significantly more endotherapy sessions. Seven patients had persistent dysplasia or progression to cancer, and 3 patients had complete eradication of HGD but presented with intramucosal carcinoma an average of 15 months after eradication. The 10 patients in whom endotherapy failed underwent salvage therapy with esophagectomy (7 patients), definitive chemoradiotherapy (1 patient), and endotherapy (2 patients). Patients treated with esophagectomy were disease free at a mean of 25 months postoperatively.

HGD on initial endoscopy, multifocal dysplasia, mucosal abnormalities, and failure to eradicate nondysplastic Barrett's metaplasia were associated with failure of endotherapy. Patients with these characteristics should be considered at higher risk for treatment failure, and earlier consideration should be given to esophagectomy if there is persistent, progressive, or recurrent neoplasia. Clinical outcomes are good, even after salvage therapy. Continued endoscopic surveillance is mandatory after successful endotherapy because of the risk of recurrent disease.