Development of Evidence-Based Surveillance Intervals After Radiofrequency Ablation of Barrett's Esophagus.

BACKGROUND & AIMS: Barrett's esophagus (BE) recurs in 25% or more of patients treated successfully with radiofrequency ablation (RFA), so surveillance endoscopy is recommended after complete eradication of intestinal metaplasia (CEIM). The frequency of surveillance is informed only by expert opinion. We aimed to model the incidence of neoplastic recurrence, validate the model in an independent cohort, and propose evidence-based surveillance intervals. METHODS: We collected data from the United States Radiofrequency Ablation Registry (US RFA, 2004-2013) and the United Kingdom National Halo Registry (UK NHR, 2007-2015) to build and validate models to predict the incidence of neoplasia recurrence after initially successful RFA. We developed 3 categories of risk and modeled intervals to yield 0.1% risk of recurrence with invasive adenocarcinoma. We fit Cox proportional hazards models assessing discrimination by C statistic and 95% confidence limits. RESULTS: The incidence of neoplastic recurrence was associated with most severe histologic grade before CEIM, age, endoscopic mucosal resection, sex, and baseline BE segment length. In multivariate analysis, a model based solely on most severe pre-CEIM histology predicted neoplastic recurrence with a C statistic of 0.892 (95% confidence limit, 0.863-0.921) in the US RFA registry. This model also performed well when we used data from the UK NHR. Our model divided patients into 3 risk groups based on baseline histologic grade: non-dysplastic BE; indefinite for dysplasia, low-grade dysplasia, and high-grade dysplasia; or intramucosal adenocarcinoma. For patients with low-grade dysplasia, we propose surveillance endoscopy at 1 and 3 years after CEIM; for patients with high-grade dysplasia or intramucosal adenocarcinoma, we propose surveillance endoscopy at 0.25, 0.5, and 1 year after CEIM, then annually. CONCLUSION: In analyses of data from the US RFA and UK NHR for BE, a much-attenuated schedule of surveillance endoscopy would provide protection from invasive adenocarcinoma. Adherence to the recommended surveillance intervals could decrease the number of endoscopies performed yet identify unresectable cancers at rates less than 1/1000 endoscopies.

Development and Validation of a Classification System to Identify High-Grade Dysplasia and Esophageal Adenocarcinoma in Barrett's Esophagus Using Narrow-Band Imaging.

BACKGROUND & AIMS: Although several classification systems have been proposed for characterization of Barrett's esophagus (BE) surface patterns based on narrow-band imaging (NBI), none have been widely accepted. The Barrett's International NBI Group (BING) aimed to develop and validate an NBI classification system for identification of dysplasia and cancer in patients with BE. METHODS: The BING working group, composed of NBI experts from the United States, Europe, and Japan, met to develop a validated, consensus-driven NBI classification system for identifying dysplasia and cancer in BE. The group reviewed 60 NBI images of nondysplastic BE, high-grade dysplasia, and esophageal adenocarcinoma to characterize mucosal and vascular patterns visible by NBI; these features were used to develop the BING criteria. We then recruited adult patients undergoing surveillance or endoscopic treatment for BE at 4 institutions in the United States and Europe, obtaining high-quality NBI images and performing histologic analysis of biopsies. Experts individually reviewed 50 NBI images to validate the BING criteria, and then evaluated 120 additional NBI images (not previously viewed) to determine whether the criteria accurately predicted the histology results. RESULTS: The BING criteria identified patients with dysplasia with 85% overall accuracy, 80% sensitivity, 88% specificity, 81% positive predictive value, and 88% negative predictive value. When dysplasia was identified with a high level of confidence, these values were 92%, 91%, 93%, 89%, and 95%, respectively. The overall strength of inter-observer agreement was substantial (κ = 0.681). CONCLUSIONS: The BING working group developed a simple, internally validated system to identify dysplasia and EAC in patients with BE based on NBI results. When images are assessed with a high degree of confidence, the system can classify BE with >90% accuracy and a high level of inter-observer agreement.

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.

Persistence of nondysplastic Barrett's esophagus identifies patients at lower risk for esophageal adenocarcinoma: results from a large multicenter cohort.

BACKGROUND & AIMS: Recent population-based studies have shown a low risk of esophageal adenocarcinoma (EAC) in patients with nondysplastic Barrett's esophagus (NDBE). We evaluated whether persistence of NDBE over multiple consecutive surveillance endoscopic examinations could be used in risk stratification of patients with Barrett's esophagus (BE). METHODS: We performed a multicenter outcomes study of a large cohort of patients with BE. Based on the number of consecutive surveillance endoscopies showing NDBE, we identified 5 groups of patients. Patients in group 1 were found to have NDBE at their first esophagogastroduodenoscopy (EGD). Patients in group 2 were found to have NDBE on their first 2 consecutive EGDs. Similarly, patients in groups 3, 4, and 5 were found to have NDBE on 3, 4, and 5 consecutive surveillance EGDs. A logistic regression model was built to determine whether persistence of NDBE independently protected against development of cancer. RESULTS: Of a total of 3515 patients with BE, 1401 patients met the inclusion criteria (93.3% white; 87.5% men; median age, 60 ±17 years). The median follow-up period was 5 ± 3.9 years (7846 patient-years). The annual risk of EAC in groups 1 to 5 was 0.32%, 0.27%, 0.16%, 0.2%, and 0.11%, respectively (P for trend = .03). After adjusting for age, sex, and length of BE, persistence of NDBE, based on multiple surveillance endoscopies, was associated with a gradually lower likelihood of progression to EAC. CONCLUSIONS: Persistence of NDBE over several endoscopic examinations identifies patients who are at low risk for development of EAC. These findings support lengthening surveillance intervals or discontinuing surveillance of patients with persistent NDBE.

Endoscopic Raman spectroscopy enables objective diagnosis of dysplasia in Barrett's esophagus.

BACKGROUND: Early detection and targeted endoscopic resection of Barrett's esophagus-associated high-grade dysplasia (HGD) can prevent progression to invasive esophageal malignancy. Raman spectroscopy, a highly sophisticated analytical technique, has been translated into an endoscopic tool to facilitate rapid, objective diagnosis of dysplasia in the esophagus. OBJECTIVE: To evaluate the ability of endoscopic Raman spectroscopy (ERS) to objectively detect esophageal HGD and adenocarcinoma. DESIGN: A total of 798 one-second spectra were measured from 673 ex vivo esophageal tissue samples, collected from patients with Barrett's esophagus by using a novel endoscopic Raman probe. Spectra were correlated with consensus histopathology. Multivariate analysis was used to evaluate the classification accuracy of ERS ex vivo. SETTING: Probe measurements were conducted in the laboratory. Tissue specimens were collected from the operating theatre and endoscopy unit. PATIENTS: Tissue from 62 patients was included in the study. INTERVENTIONS: Endoscopic biopsy/resection or esophagectomy was performed where indicated clinically. MAIN OUTCOME MEASUREMENT: Diagnostic performance of ERS for detection of HGD and esophageal adenocarcinoma. RESULTS: ERS demonstrated a sensitivity of 86% and a specificity of 88% for detecting HGD and adenocarcinoma. The ability to grade dysplasia and differentiate intestinal metaplasia from nonintestinal metaplasia columnar-lined esophagus was also demonstrated. Diagnostic classification was based on objective measurement of the biochemical profile of different tissue types. The potential for combination ERS and narrow-band imaging was also demonstrated. LIMITATIONS: Measurements were taken from ex vivo tissue. CONCLUSION: ERS enables rapid, accurate, objective diagnosis of superficial esophageal disease (metaplasia, dysplasia, intramucosal cancer) in clinically applicable time scales.

Association between length of Barrett's esophagus and risk of high-grade dysplasia or adenocarcinoma in patients without dysplasia.

BACKGROUND & AIMS: It is not clear whether length of Barrett's esophagus (BE) is a risk factor for high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) in patients with nondysplastic BE. We studied the risk of progression to HGD or EAC in patients with nondysplastic BE, based on segment length. METHODS: We analyzed data from a large cohort of patients participating in the BE Study-a multicenter outcomes project comprising 5 US tertiary care referral centers. Histologic changes were graded as low-grade dysplasia, HGD, or EAC. The study included patients with BE of documented length without dysplasia and at least 1 year of follow-up evaluation (n = 1175; 88% male), and excluded patients who developed HGD or EAC within 1 year of their BE diagnosis. The mean follow-up period was 5.5 y (6463 patient-years). The annual risk of HGD and EAC was plotted in 3-cm increments (≤3 cm, 4-6 cm, 7-9 cm, 10-12 cm, and ≥13 cm). We calculated the association between time to progression and length of BE. RESULTS: The mean BE length was 3.6 cm; 44 patients developed HGD or EAC, with an annual incidence rate of 0.67%/y. Compared with nonprogressors, patients who developed HGD or EAC had longer BE segments (6.1 vs 3.5 cm; P < .001). Logistic regression analysis showed a 28% increase in risk of HGD or EAC for every 1-cm increase in BE length (P = .01). Patients with BE segment lengths of 3 cm or shorter took longer to develop HGD or EAC than those with lengths longer than 4 cm (6 vs 4 y; P = nonsignificant). CONCLUSIONS: In patients with BE without dysplasia, length of BE was associated with progression to HGD or EAC. The results support the development of a risk stratification scheme for these patients based on length of BE segment.

Efficacy and durability of radiofrequency ablation for Barrett's Esophagus: systematic review and meta-analysis.

BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.