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Background: Little is known about differences in Barrett's esophagus (BE) characteristics by sex and race and/or ethnicity or these differences in response to radiofrequency ablation (RFA)., Objective: We compared disease-specific characteristics, treatment efficacy, and safety outcomes by sex and race and/or ethnicity in patients treated with RFA for BE., Design: The U.S. RFA patient registry is a multicenter collaboration reporting processes and outcomes of care for patients treated with RFA for BE., Patients: Patients enrolled with BE., Interventions: RFA., Main Outcome Measurements: We assessed safety (stricture, bleeding, perforation, hospitalization), efficacy (complete eradication of intestinal metaplasia [CEIM]), complete eradication of dysplasia, and number of treatments to CEIM by sex and race and/or ethnicity., Results: Among 5521 patients (4052 men; 5126 white, 137 Hispanic, 82 African American, 40 Asian, 136 heritage not identified), women were younger (60.0 vs 62.1 years) and had shorter BE segments (3.2 vs 4.4 cm) and less dysplasia (37% vs 57%) than did men. Women were almost twice as likely to stricture (odds ratio 1.7; 95% confidence interval, 1.2-2.3). Although white patients were predominantly male, about half of African Americans and Asians with BE were female. African Americans and Asians had less dysplasia than white patients. Asians and African Americans had more strictures than did white patients. There were no sex or race differences in efficacy., Limitations: Observational study with non-mandated paradigms, no central laboratory for reinterpretation of pathology., Conclusion: In the U.S. RFA patient registry, women had shorter BE segments and less-aggressive histology. The usual tendency toward BE in men was absent in African Americans and Asians. Posttreatment stricture was more common among women and Asians. RFA efficacy did not differ by sex or race., (Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Radiofrequency ablation (RFA) can eradicate dysplasia and intestinal metaplasia in patients with dysplastic Barrett's esophagus (BE), and reduce rates of esophageal adenocarcinoma. We assessed long-term rates of eradication, durability of neosquamous epithelium, disease progression, and safety of RFA in patients with dysplastic BE., Methods: We performed a randomized trial of 127 subjects with dysplastic BE; after cross-over subjects were included, 119 received RFA. Subjects were followed for a mean time of 3.05 years; the study was extended to 5 years for patients with eradication of intestinal metaplasia at 2 years. Outcomes included eradication of dysplasia or intestinal metaplasia after 2 and 3 years, durability of response, disease progression, and adverse events., Results: After 2 years, 101 of 106 patients had complete eradication of all dysplasia (95%) and 99 of 106 had eradication of intestinal metaplasia (93%). After 2 years, among subjects with initial low-grade dysplasia, all dysplasia was eradicated in 51 of 52 (98%) and intestinal metaplasia was eradicated in 51 of 52 (98%); among subjects with initial high-grade dysplasia, all dysplasia was eradicated in 50 of 54 (93%) and intestinal metaplasia was eradicated in 48 of 54 (89%). After 3 years, dysplasia was eradicated in 55 of 56 of subjects (98%) and intestinal metaplasia was eradicated in 51 of 56 (91%). Kaplan-Meier analysis showed that dysplasia remained eradicated in >85% of patients and intestinal metaplasia in >75%, without maintenance RFA. Serious adverse events occurred in 4 of 119 subjects (3.4%); the rate of stricture was 7.6%. The rate of esophageal adenocarcinoma was 1 per 181 patient-years (0.55%/patient-years); there was no cancer-related morbidity or mortality. The annual rate of any neoplastic progression was 1 per 73 patient-years (1.37%/patient-years)., Conclusions: In subjects with dysplastic BE, RFA therapy has an acceptable safety profile, is durable, and is associated with a low rate of disease progression, for up to 3 years., (Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: After endoscopic radiofrequency ablation (RFA) of dysplastic Barrett's esophagus (BE), endoscopic biopsy samples are obtained to assess response to therapy. Whether these biopsies are of adequate depth to assess efficacy is unknown., Objective: To compare the depth of endoscopic biopsy samples after RFA with those of untreated controls and to determine the prevalence of subepithelial structures in endoscopic biopsy fragments., Design: Secondary analysis of the AIM Dysplasia Trial, a multicenter, randomized, sham-controlled study., Setting: Nineteen treatment centers., Patients: Subjects with dysplastic BE, either status post RFA or ablation naïve (sham)., Main Outcome Measurements: The proportion of biopsy samples demonstrating subepithelial structures, stratified by tissue type (columnar vs squamous) in sham- and RFA-treated subjects., Results: A total of 5648 biopsy fragments were analyzed from 113 subjects (78 RFA, 35 sham; mean 50.0 fragments per subject). Most fragments (4653, 82.4%) contained subepithelium. Squamous biopsy samples from RFA and sham subjects demonstrated subepithelium at similar rates (78.4% vs 79.1%, respectively, P = not significant [NS]). Columnar biopsy samples from RFA and sham subjects also included subepithelium at similar rates (99.0% vs 98.8%, respectively, P = NS). Regardless of treatment assignment, more columnar than squamous biopsy samples demonstrated subepithelium (98.8% vs 78.5%, P < .001)., Limitations: Biopsy samples were not individually mounted., Conclusions: In both squamous and columnar tissue, endoscopic biopsy samples after RFA were as likely to demonstrate subepithelium as untreated controls. Almost 80% of all biopsy samples were adequate to evaluate for subsquamous intestinal metaplasia. The primary determinant of biopsy depth is the type of epithelium that underwent biopsy, with squamous less likely to yield subepithelium than columnar. Biopsy samples after RFA appear to be of adequate depth to assess response to therapy. (Clinical trial registration number NCT00282672.)., (Copyright 2010 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Non-dysplastic mucosa (ND-) in Barrett's esophagus (BE) shows clonal molecular aberrations, loss of cell cycle control, and other features of "neoplasia." These changes occur prior to morphologic expression of neoplasia (dysplasia). Morphologic evaluation of dysplasia is fraught with error, and, as a result, often leads to false-negative and false-positive diagnoses. Early "crypt dysplasia" is difficult to detect, and is often missed in routine biopsy specimens. Some studies show substantial progression rates of low-grade dysplasia (LGD), and crypt dysplasia, to esophageal adenocarcinoma (EAC). Dysplasia, even when fully developed, may, in certain circumstances, be difficult to differentiate from non-dysplastic (regenerating) BE. Radiofrequency ablation (RFA) is a safe and effective method for removing mucosa at risk of cancer. Given the difficulties of dysplasia assessment in mucosal biopsies, and the molecular characteristics of ND-BE, this technique should be considered for treatment of all BE patients, including those with ND or LGD. Post-ablation neo-squamous epithelium reveals no molecular abnormalities, and is biologically stable. Given that prospective randomized controlled trials of ablative therapy for ND-BE aiming at reducing EAC incidence and mortality are unlikely to be completed in the near future, endoscopic ablation is a valid management option. The success of RFA in achieving safe, uniform, reliable, and predictable elimination of BE allows surgeons to combine fundoplication with RFA. Currently, there is no type of treatment for dysplastic or non-dysplastic BE that achieves a complete response in 100% of patients, eliminates all risk of developing cancer, results in zero adverse events, is less expensive in terms of absolute costs than surveillance, is durable for 20+ years, or eliminates the need for surveillance. Regardless, RFA shows established safety, efficacy, durability, and cost-effective profiles that should be considered in the management of patients with non-dysplastic or low-grade dysplastic BE.

Background: The management strategies for Barrett's esophagus (BE) that contains high-grade dysplasia (HGD) include intensive endoscopic surveillance, photodynamic therapy, thermal ablation, EMR, and esophagectomy., Objective: To assess the safety and effectiveness of endoscopic circumferential balloon-based ablation by using radiofrequency energy for treating BE HGD., Design: Multicenter U.S. registry., Setting: Sixteen academic and community centers; treatment period from September 2004 to March 2007., Patients: Patients with histologic evidence of intestinal metaplasia (IM) that contained HGD confirmed by at least 2 expert pathologists. A prior EMR was permitted, provided that residual HGD remained in the BE region for ablation., Intervention: Endoscopic circumferential ablation with follow-up esophageal biopsies to assess the histologic response to treatment., Outcomes: Histologic complete response (CR) end points: (1) all biopsy specimen fragments obtained at the last biopsy session were negative for HGD (CR-HGD), (2) all biopsy specimens were negative for any dysplasia (CR-D), and (3) all biopsy specimens were negative for IM (CR-IM)., Results: A total of 142 patients (median age 66 years, interquartile range [IQR] 59-75 years) who had BE HGD (median length 6 cm, IQR 3-8 cm) underwent circumferential ablation (median 1 session, IQR 1-2). No serious adverse events were reported. There was 1 asymptomatic stricture and no buried glands. Ninety-two patients had at least 1 follow-up biopsy session (median follow-up 12 months, IQR 8-15 months). A CR-HGD was achieved in 90.2% of patients, CR-D in 80.4%, and CR-IM in 54.3%., Limitations: A nonrandomized study design, without a control arm, a lack of centralized pathology review, ablation and biopsy technique not standardized, and a relatively short-term follow-up., Conclusions: Endoscopic circumferential ablation is a promising modality for the treatment of BE that contains HGD. In this multicenter registry, the intervention safely achieved a CR for HGD in 90.2% of patients at a median of 12 months of follow-up.

Background: Barrett's esophagus (BE) with high-grade dysplasia (HGD) is a risk factor for development of esophageal carcinoma. Photodynamic therapy (PDT) with Photofrin (PHO) has been used to eliminate HGD in BE., Objective: Our purpose was to compare PHOPDT plus omeprazole with omeprazole only (OM)., Design: Five-year follow-up of a randomized, multicenter, multinational, pathology-blinded HGD trial., Setting: 30 sites in 4 countries., Patients: 208., Interventions: Patients with BE and HGD were randomized (2:1) to PHOPDT (n=138) or OM (n=70) into a 2-year trial followed up for 3 more years. PHOPDT patients received 2 mg/kg PHO intravenously followed by endoscopic laser light exposure of Barrett's mucosa at a wavelength of 630 nm within 40 to 50 hours to a maximum of 3 courses at least 90 days apart. Both groups received 20 mg of OM twice daily. Pathologists at one center assessed biopsy specimens in a blinded fashion., Main Outcome Measurement: HGD ablation status over 5 years of follow-up., Results: At 5 years PHOPDT was significantly more effective than OM in eliminating HGD (77% [106/138] vs 39% [27/70], P<.0001). A secondary outcome measure preventing progression to cancer showed a significant difference (P=.027) with about half the likelihood of cancer occurring in PHOPDT (21/138 [15%]) compared with OM (20/70 [29%]), with a significantly (P=.004) longer time to progression to cancer favoring PHOPDT., Limitations: Not all patients were available for follow-up., Conclusions: This 5-year randomized trial of BE patients with HGD demonstrates that PHOPDT is a clinically and statistically effective therapy in producing long-term ablation of HGD and reducing the potential impact of cancer compared with OM.

Porfimer sodium photodynamic therapy (ps-PDT) for Barrett's esophagus is a powerful endoscopic treatment that can eliminate high-grade dysplasia (HGD) and Barrett's mucosa and reduce the risk of development of cancer in these patients. Ps-PDT typically results in destruction of Barrett's esophagus in the majority of the treated area. However, residual small island of Barrett's mucosa may persist after PDT. Therefore, adjuvant thermal ablation should be available during follow-up endoscopies for ablation of residual islands of Barrett's mucosa. PDT should be applied concurrent with effective proton pump inhibitor therapy. This article provides a practical guide for application of porfimer sodium balloon PDT for management of Barrett's esophagus with HGD. Recommendations are provided for patient selection and screening, delivery of PDT to include light dosimetry, methodology for follow-up endoscopies, as well as discussing the potential side effects and complications., (Copyright 2006 Wiley-Liss, Inc.)

Background: Barrett's esophagus (BE) may lead to high-grade dysplasia (HGD) and adenocarcinoma. The objective was to examine the impact of treating patients with BE and with HGD by using porfimer sodium (POR) and photodynamic therapy (PDT) for ablating HGD and reducing the incidence of esophageal adenocarcinoma., Methods: The design was a multicenter, partially blinded (pathology), randomized clinical trial conducted in patients with BE who have HGD. There were 30 contributing centers. A total of 485 patients were screened, with 208 in the intent-to-treat population and 202 in the safety population. Patients were randomized on a 2:1 basis to compare PDT with POR plus omeprazole (PORPDT) with omeprazole only (OM). The main outcome measurement was complete HGD ablation occurring at any time during the study period., Results: There was a significant difference (p < 0.0001) in favor of PORPDT (106/138 [77%]) compared with OM (27/70 [39%]) in complete ablation of HGD at any time during the study period. The occurrence of adenocarcinoma in the PORPDT group (13%) (n=18) was significantly lower (p < 0.006) compared with the OM group (28%) [corrected] (n=20). The safety profile showed 94% of patients in the PORPDT group and 13% of patients in the OM group had treatment-related adverse effects. The limitations of the study were that PDT therapy may have had to be applied more than once and that patients spent more time in treatment. The patients and the physicians were not blinded to the treatment., Conclusions: PORPDT in conjunction with omeprazole is an effective therapy for ablating HGD in patients with BE and in reducing the incidence of esophageal adenocarcinoma.

Photodynamic therapy using a centering balloon was recently approved by the Food and Drug Administration for ablation of Barrett esophagus with high-grade dysplasia. This article is an educational tool for the photodynamic therapy team, addressing four important steps involved with photodynamic therapy: screening for potential patients, patient education, treatment using the centering balloon, and follow-up after treatment. Each step ensures proper care for the patient requiring photodynamic therapy.

Background: Multiple treatment strategies for subjects with high grade dysplasia (HGD) in Barrett's oesophagus (BO) have been suggested. However, it is unclear which of these strategies provides the greatest life expectancy, and the costs associated with the management strategies are unknown., Aim: To compare the efficacy and cost effectiveness of competing management strategies for BO with HGD., Methods: We created a decision analysis model in Data 4.0 to assess possible treatment strategies for BO with HGD. The strategies included: (1) no preventative strategy, (2) elective surgical oesophagectomy, (3) endoscopic ablation, and (4) surveillance endoscopy. The base case was a healthy 50 year old White male with an initial diagnosis of BO with HGD. The model allowed for complications of surgery, including death. Ablative therapy could cause stricture or perforation. Pathological misinterpretation was allowed, and modelled after reported rates. Estimates were derived from the literature for the rate of progression of HGD to cancer and for complication rates for the various treatment modalities. The endoscopic ablation arm was modelled as photodynamic therapy. Sensitivity analyses were performed over a wide range of cancer incidences, complication rates, and procedure costs., Results: Endoscopic ablation was the most effective strategy, yielding 15.5 discounted quality adjusted life years (dQALY), compared with 15.0 for endoscopic surveillance and 14.9 for oesophagectomy. No preventative strategy was the most inexpensive option, yielding an average cost per quality adjusted life year of US dollars 54 (44) per dQALY, but resulted in high rates of cancer. Endoscopic surveillance dominated oesophagectomy, being both less costly and more effective. The condition of extended dominance occurred when comparing endoscopic ablation to endoscopic surveillance because, although the total costs of ablation were greater than those of surveillance, it was less expensive to buy an additional life year using endoscopic ablation than endoscopic surveillance. The incremental cost effectiveness ratio when moving from no therapy to ablative therapy was a reasonable US dollars 25 621/dQALY (21 009/dQALY). Sensitivity analysis demonstrated that when yearly rates of progression to cancer from HGD exceeded 30%, oesophagectomy became the most cost effective option., Conclusions: A strategy of endoscopic ablation provided the longest quality adjusted life expectancy for BO with HGD. Although endoscopic surveillance was less expensive than endoscopic ablation, it was associated with shorter survival. Optimal utilisation of healthcare resources may be achieved with endoscopic ablative therapy for BO with HGD.

Background: Photodynamic therapy has been shown to eliminate Barrett's dysplasia. This report presents long-term follow-up data after photodynamic therapy of Barrett's esophagus with high-grade dysplasia, low-grade dysplasia, or early stage carcinoma., Methods: Porfimer-photodynamic therapy was performed in 103 patients. The Nd:YAG laser was used to photoablate small areas of residual or untreated Barrett's mucosa. Acid suppression was maintained in all patients (omeprazole, 20 mg twice a day)., Results: Mean follow-up was 50.65 (SD 20.57) months (range 2-122 months). For the 82 patients not lost to follow-up, mean follow-up was 58.5 (12.89) months (range 41-132 months). After photodynamic therapy, the length of Barrett's mucosa decreased by a mean of 6.92 cm (range 1-22 cm). Of the 65 patients with high-grade dysplasia, 60 (94%) had elimination of high-grade dysplasia. Three (4.6%) patients developed subsquamous adenocarcinoma. Subsquamous, nondysplastic, metaplastic epithelium was found in 4 patients (4.9%). Strictures occurred in 18% with one session of photodynamic therapy, and 50% with two treatments, 30% overall. For the 103 patients, intention-to-treat success rates were 92.9%, 77.5%, and 44.4% for, respectively, low-grade dysplasia, high-grade dysplasia, and early stage carcinoma groups., Conclusion: Porfimer-photodynamic therapy with supplemental Nd:YAG photoablation and continuous treatment with omeprazole reduces the length of Barrett's mucosa, eliminates high-grade dysplasia, and, by comparison with historical data, may reduce the expected frequency of carcinoma.