Cary C. Cotton

Intestinal metaplasia recurs infrequently in patients successfully treated for Barrett's esophagus with radiofrequency ablation.

OBJECTIVES:Radiofrequency ablation (RFA) of Barretts esophagus (BE) is safe and effective in eradicating dysplasia and intestinal metaplasia, and may reduce rates of esophageal adenocarcinoma (EAC). We assessed rates of and risk factors for disease recurrence after successful treatment of BE with RFA.METHODS:We performed a retrospective cohort study of patients who completed RFA for dysplastic BE or intramucosal carcinoma (IMC), achieved complete eradication of dysplasia (CE-D) or intestinal metaplasia (CE-IM), and underwent subsequent endoscopic surveillance at a single center. Rates of disease recurrence and progression were determined. Patients with and without recurrent disease were compared to determine risk factors for recurrence.RESULTS:Two hundred and sixty-two subjects underwent RFA during the study period. Of these, 119 and 112 patients were retained in endoscopic surveillance after CE-D and CE-IM, respectively. Median observation time was 397 days (range: 54–1,668 days). Eight patients (7% of those with CE-IM) had recurrent disease after a median of 235 days (range 55–1,124 days). Progression to IMC (n=1) or EAC (n=2) occurred in three of these eight patients, all of whom had pre-ablation high-grade dysplasia (HGD). Five patients had recurrence of non-dysplastic BE (n=3), low-grade dysplasia (n=1), and HGD (n=1). During 155 patient-years of observation, recurrence occurred in 5.2%/year, and progression occurred in 1.9%/year. No clinical characteristics were associated with disease recurrence.CONCLUSIONS:In patients with BE and dysplasia or early cancer who achieved CE-IM, BE recurred in ∼5%/year. Patient characteristics did not predict recurrence. Subjects undergoing RFA for dysplastic BE should be retained in endoscopic surveillance.

Safety and efficacy of endoscopic mucosal therapy with radiofrequency ablation for patients with neoplastic Barrett's esophagus.

BACKGROUND & AIMS The goal of radiofrequency ablation (RFA) for patients with Barretts esophagus (BE) is to eliminate dysplasia and metaplasia. The efficacy and safety of RFA for patients with BE and neoplasia are characterized incompletely. METHODS We performed a retrospective study of 244 patients treated with RFA for BE with dysplasia or intramucosal carcinoma. Efficacy outcomes were complete eradication of intestinal metaplasia (CEIM), complete eradication of dysplasia, total treatments, and RFA sessions. Safety outcomes included death, perforation, stricture, bleeding, and hospitalization. We identified factors associated with incomplete EIM and stricture formation. RESULTS CEIM was achieved in 80% of patients, and complete eradication of dysplasia was achieved in 87%; disease progressed in 4 patients. A higher percentage of patients with incomplete EIM were female (40%) than those with CEIM (20%; P = .045); patients with incomplete EIM also had a longer segment of BE (5.5 vs 4.0 cm; P = .03), had incomplete healing between treatment sessions (45% vs 15%; P = 0.004), and underwent more treatment sessions (4 vs 3; P = .007). Incomplete healing was associated independently with incomplete EIM. Twenty-three patients (9.4%) had a treatment-related complication during 777 treatment sessions (3.0%), including strictures (8.2%), postprocedural hemorrhages (1.6%), and hospitalizations (1.6%). Patients who developed strictures were more likely to use nonsteroidal anti-inflammatory drugs than those without strictures (70% vs 45%; P = .04), have undergone antireflux surgery (15% vs 3%; P = .04), or had erosive esophagitis (35% vs 12%; P = .01). CONCLUSIONS RFA is highly effective and safe for treatment of BE with dysplasia or early stage cancer. Strictures were the most common complications. Incomplete healing between treatment sessions was associated with incomplete EIM. Nonsteroidal anti-inflammatory drug use, prior antireflux surgery, and a history of erosive esophagitis predicted stricture formation.

Focal endoscopic mucosal resection before radiofrequency ablation is equally effective and safe compared with radiofrequency ablation alone for the eradication of Barrett's esophagus with advanced neoplasia

BACKGROUND EMR is commonly performed before radiofrequency ablation (RFA) for nodular dysplastic Barretts esophagus (BE). OBJECTIVE To determine the efficacy and safety of EMR before RFA for nodular BE with advanced neoplasia (high-grade dysplasia [HGD] or intramucosal carcinoma [IMC]). DESIGN Retrospective study. SETTING University of North Carolina Hospitals, from 2006 to 2011. PATIENTS 169 patients with BE with advanced neoplasia: 65 patients treated with EMR and RFA for nodular disease and 104 patients treated with RFA alone for nonnodular disease. INTERVENTIONS EMR, RFA. MAIN OUTCOME MEASUREMENTS Efficacy (complete eradication of dysplasia, complete eradication of intestinal metaplasia, total treatment sessions, RFA treatment sessions), safety (stricture formation, bleeding, and hospitalization). RESULTS EMR followed by RFA achieved complete eradication of dysplasia and complete eradication of intestinal metaplasia in 94.0% and 88.0% of patients, respectively, compared with 82.7% and 77.6% of patients, respectively, in the RFA-only group (P = .06 and P = .13, respectively). The complication rates between the 2 groups were similar (7.7% vs 9.6%, P = .79). Strictures occurred in 4.6% of patients in the EMR-before-RFA group. compared with 7.7% of patients in the RFA-only group (P = .53). LIMITATIONS Retrospective study at a tertiary-care referral center. CONCLUSION In patients treated with EMR before RFA for nodular BE with HGD or IMC, no differences in efficacy and safety outcomes were observed compared with RFA alone for nonnodular BE with HGD or IMC. EMR followed by RFA is safe and effective for patients with nodular BE and advanced neoplasia.

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 Barretts 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.

Outcomes of Esophageal Dilation in Eosinophilic Esophagitis: Safety, Efficacy, and Persistence of the Fibrostenotic Phenotype

Objectives:Esophageal dilation is commonly performed in eosinophilic esophagitis (EoE), but there are few long-term data. The aims of this study were to assess the safety and long-term efficacy of esophageal dilation in a large cohort of EoE cases, and to determine the frequency and predictors of requiring multiple dilations.Methods:We conducted a retrospective cohort study in the University of North Carolina EoE Clinicopathological Database from 2002 to 2014. Included subjects met consensus diagnostic criteria for EoE. Clinical, endoscopic, and histologic features were extracted, as were dilation characteristics (dilator type, change in esophageal caliber, and total number of dilations) and complications. Patients with EoE who had undergone dilation were compared with those who did not and also stratified by whether they required single or multiple dilations.Results:Of 509 EoE patients, 164 were dilated a total of 486 times. Those who underwent dilation had a longer duration of symptoms before diagnosis (11.1 vs. 5.4 years, P<0.001). Ninety-five patients (58%) required >1 dilation (417 dilations total, mean of 4.4±4.3 per patient). The only predictor of requiring multiple dilations was a smaller baseline esophageal diameter. Dilation was tolerated well, with no major bleeds, perforations, or deaths. The overall complication rate was 5%, primarily due to post-procedural pain. Of 164 individuals dilated, a majority (58% or 95/164) required a second dilation. Of these individuals, 75% required repeat dilation within 1 year.Conclusions:Dilation in EoE is well-tolerated, with a very low risk of serious complications. Patients with long-standing symptoms before diagnosis are likely to require dilation. More than half of those dilated will require multiple dilations, often needing a second procedure within 1 year. These findings can be used to counsel patients with fibrostenotic complications of EoE.

Original ResearchFull Report: Clinical—Alimentary TractIncidence of Esophageal Adenocarcinoma and Causes of Mortality After Radiofrequency Ablation of Barrett’s Esophagus

BACKGROUND & AIMS Radiofrequency ablation (RFA) is commonly used to treat Barretts 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.

Effects of the Learning Curve on Efficacy of Radiofrequency Ablation for Barrett’s Esophagus

BACKGROUND & AIMS Complete eradication of Barretts esophagus (BE) often requires multiple sessions of radiofrequency ablation (RFA). Little is known about the effects of case volume on the safety and efficacy of RFA or about the presence or contour of learning curves for this procedure. METHODS We collected data from the US RFA Patient Registry (from 148 institutions) for patients who underwent RFA for BE from July 2007 to July 2011. We analyzed the effects of the number of patients treated by individual endoscopists and individual centers on safety and efficacy outcomes of RFA. Outcomes, including stricture, bleeding, hospitalization, and complete eradication of intestinal metaplasia (CEIM), were assessed using logistic regression. The effects of center and investigator experience on numbers of treatment sessions to achieve CEIM were examined using linear regression. RESULTS After we controlled for potential confounders, we found that as the experience of endoscopists and centers increased with cases, the numbers of treatment sessions required to achieve CEIM decreased. This relationship persisted after adjusting for patient age, sex, race, length of BE, and presence of pretreatment dysplasia (P < .01). Center experience was not significantly associated with overall rates of CEIM or complete eradication of dysplasia. We did not observe any learning curve with regard to risks of stricture, gastrointestinal bleeding, perforation, or hospitalization (P > .05). CONCLUSIONS Based on analysis of a large multicenter registry, efficiency of the treatment, as measured by number of sessions needed to achieve CEIM, increased with case volume, indicating a learning curve effect. This trend began to disappear after treatment of approximately 30 patients by the center or individual endoscopist. However, there was no significant association between safety or efficacy outcomes and previous case volume.

Clinical Outcomes Following Recurrence of Intestinal Metaplasia After Successful Treatment of Barrett’s Esophagus With Radiofrequency Ablation

Objectives:Radiofrequency ablation (RFA) is an effective treatment for Barrett’s esophagus (BE). However, recurrence of BE after initially successful RFA is common, and outcomes following recurrence not well described. We report the outcomes associated with recurrence following initially successful RFA.Methods:We performed a retrospective cohort study of 306 patients treated with RFA for dysplastic BE. Complete eradication of intestinal metaplasia (CE-IM) was defined as complete histological and endoscopic remission of IM. Recurrence was defined as any presence of IM or dysplasia in the tubular esophagus or dysplasia in the gastric cardia subsequent to CE-IM. We examined rates and risk factors for recurrence, dysplastic recurrence, and invasive adenocarcinoma after CE-IM. We also describe the clinical course of patients following recurrence.Results:Of the 306 eligible patients undergoing RFA, 218 achieved CE-IM and also had subsequent surveillance endoscopy. Of these, 52 (24%) experienced recurrence of IM or Barrett’s-associated neoplasia over 540.6 person-years (incidence rate 9.6%/year). Thirty (58%) of these achieved second CE-IM; 4 (1.8% of total, 7.7% of recurrences) ultimately progressed to invasive adenocarcinoma (incidence rate 0.65%/year). Longer Prague M was a strong risk factor for invasive adenocarcinoma (rate ratio of 1.34/cm). Most dysplastic recurrences were in the cardia, and the majority were not visible but detected on random biopsies.Conclusions:Most patients with recurrent BE after initially successful RFA achieve second CE-IM; however, 1.8% progressed to invasive adenocarcinoma. Longer Prague M was predictive of invasive adenocarcinoma. Four-quadrant random biopsy of the cardia is advisable during surveillance endoscopy after CE-IM.

Six-Food Elimination Diet and Topical Steroids are Effective for Eosinophilic Esophagitis: A Meta-Regression

BackgroundTopical corticosteroids or six-food elimination diet is recommended as initial therapy for eosinophilic esophagitis (EoE).AimsWe aimed to summarize published manuscripts that report outcomes of these therapies for EoE.MethodsWe performed a systematic review in MEDLINE, Web of Science, and Embase of published manuscripts describing topical fluticasone, topical budesonide, and six-food elimination diet as therapies for EoE. We conducted meta-analysis of symptom improvement and the change in peak mucosal eosinophil count, with heterogeneity between studies examined with meta-regression analysis.ResultsSystematic review yielded 51 articles that met inclusion criteria. Summary histologic response rates were 68.3% [95% prediction limits (PL) 16.2–96.0%] for fluticasone, 76.8% (95% PL 36.1–95.1%) for budesonide, and 69.0% (95% PL 31.9–91.4%) for six-food elimination diet. Corresponding decreases in eosinophil counts were 37.8 (95% PL 19.0–56.7), 62.5 (95% PL 125.6 to −0.67, and 44.6 (95% PL 26.5–62.7), respectively. Symptom response rates were 82.3% (95% PL 68.1–91.1%), 87.9% (95% PL 42.7–98.6%), and 87.3% (95% PL 64.5–96.3%), respectively. Meta-regression analyses decreased the initially large estimate of residual heterogeneity and suggested differences in histologic response rate associated with study populations’ baseline eosinophil count and age.ConclusionsThe literature describing topical corticosteroids and six-food elimination diet consists of small studies with diverse methods and population characteristics. Meta-analysis with meta-regression shows initial histologic and symptomatic response rates on the same order of magnitude for topical corticosteroids and six-food elimination diet, but heterogeneity of study designs prevents direct comparison of modalities.

Cost Utility Analysis of Topical Steroids Compared With Dietary Elimination for Treatment of Eosinophilic Esophagitis

Background & Aims Topical corticosteroids or dietary elimination are recommended as first‐line therapies for eosinophilic esophagitis, but data to directly compare these therapies are scant. We performed a cost utility comparison of topical corticosteroids and the 6‐food elimination diet (SFED) in treatment of eosinophilic esophagitis, from the payer perspective. Methods We used a modified Markov model based on current clinical guidelines, in which transition between states depended on histologic response simulated at the individual cohort‐member level. Simulation parameters were defined by systematic review and meta‐analysis to determine the base‐case estimates and bounds of uncertainty for sensitivity analysis. Meta‐regression models included adjustment for differences in study and cohort characteristics. Results In the base‐case scenario, topical fluticasone was about as effective as SFED but more expensive at a 5‐year time horizon (