Translational Approach to Predicting the Efficacy of Maraviroc-Based Regimens as HIV Preexposure Prophylaxis.

Maraviroc-based regimens have been explored as preexposure prophylaxis (PrEP) against human immunodeficiency virus (HIV). In this study, we utilized mucosal tissue drug exposure data, combined with target concentrations generated in vitro, in a pharmacokinetic-pharmacodynamic analysis to predict the effects of drug combinations and adherence on PrEP efficacy. Mucosal tissue concentrations of maraviroc were measured in 24 healthy women. The 90% effective concentrations (EC90) of maraviroc (alone and combined with tenofovir and emtricitabine) for protection against HIV were identified in CD4+ T cells. Monte Carlo simulations were performed to identify dosing strategies to protect colorectal and female genital tract (FGT) tissues from HIV infection. Colorectal maraviroc concentrations were 350-fold higher than in the FGT. Under steady-state conditions, our model predicted that one 300-mg dose/week was sufficient to protect colorectal tissue from HIV in 99% of the population, while 300 mg daily would protect the FGT in only 63% of the population. FGT protection increased to >90% when maraviroc was used in combination with tenofovir (5 doses/week) or emtricitabine (3 doses/week). Poor adherence resulted in a drastic decrease in efficacy in the FGT but not colorectal tissue. However, greater forgiveness was seen when maraviroc was combined with tenofovir or emtricitabine, suggesting that maraviroc should not be used alone as PrEP.

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.

Medical Treatment of Gastroesophageal Reflux Disease.

Medical treatment is effective in the majority of patients with gastroesophageal reflux disease (GERD). Lifestyle modifications are often recommended for patients with GERD, although the data supporting lifestyle recommendations are limited. Antacids are often used to treat the symptoms of GERD, but their effect is short-lived. H2-receptor antagonists and proton-pump inhibitors provide more effective options for remission of GERD symptoms and healing of esophagitis. Prokinetic medications (e.g., metoclopramide) have not been proven to help in the control of symptoms. Baclofen, which inhibits transient lower esophageal sphincter relaxations, provide an additional option for patients with persistent symptoms related to GERD; however its use is limited by side effects. Long-term medical therapy for GERD should be tailored to each patient to provide symptomatic control and maintain esophageal mucosal healing.

A Translational Pharmacology Approach to Predicting Outcomes of Preexposure Prophylaxis Against HIV in Men and Women Using Tenofovir Disoproxil Fumarate With or Without Emtricitabine.

BACKGROUND: A novel translational pharmacology investigation was conducted by combining an in vitro efficacy target with mucosal tissue pharmacokinetic (PK) data and mathematical modeling to determine the number of doses required for effective human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP). METHODS: A PK/pharmacodynamic (PD) model was developed by measuring mucosal tissue concentrations of tenofovir, emtricitabine, their active metabolites (tenofovir diphosphate [TFVdp] and emtricitabine triphosphate [FTCtp], respectively), and competing endogenous nucleotides (dATP and dCTP) in 47 healthy women. TZM-bl and CD4(+) T cells were used to identify 90% effective concentration (EC90) ratios of TFVdp to dATP and FTCtp to dCTP (alone and in combination) for protection against HIV. Monte-Carlo simulations were then performed to identify minimally effective dosing strategies to protect lower female genital tract and colorectal tissues. RESULTS: The colorectal TFVdp concentration was 10 times higher than that in the lower female genital tract, whereas concentrations of endogenous nucleotides were 7-11 times lower. Our model predicted that ≥98% of the population achieved protective mucosal tissue exposure by the third daily dose of tenofovir disoproxil fumarate plus emtricitabine. However, a minimum adherence to 6 of 7 doses/week (85%) was required to protect lower female genital tract tissue from HIV, while adherence to 2 of 7 doses/week (28%) was required to protect colorectal tissue. CONCLUSIONS: This model is predictive of recent PrEP trial results in which 2-3 doses/week was 75%-90% effective in men but ineffective in women. These data provide a novel approach for future PrEP investigations that can optimize clinical trial dosing strategies.

A Clinical Prediction Tool Identifies Cases of Eosinophilic Esophagitis Without Endoscopic Biopsy: A Prospective Study.

OBJECTIVES: Eosinophilic esophagitis (EoE) is difficult to distinguish from gastroesophageal reflux (GERD) and other causes of dysphagia. We assessed the utility of a set of clinical and endoscopic features for predicting EoE without obtaining esophageal biopsies. METHODS: We prospectively enrolled consecutive adults undergoing outpatient upper endoscopy at the University of North Carolina from July 2011 through December 2013. Incident cases of EoE were diagnosed per consensus guidelines. Non-EoE controls had either GERD- or dysphagia-predominant symptoms. A predictive model containing clinical and endoscopic, but no histological, data was assessed. Receiver operator characteristic curves were constructed and the area under the curve (AUC) was calculated. RESULTS: A total of 81 EoE cases (mean age 38 years; 60% male; 93% white; 141 eosinophils per high-power field (eos/hpf)) and 144 controls (mean age 52, 38% male; 82% white; 3 eos/hpf) were enrolled. A combination of clinical (age, sex, dysphagia, food allergy) and endoscopic (rings, furrows, plaques, hiatal hernia) features was highly predictive of EoE. The AUC was 0.944, with sensitivity, specificity, and accuracy of 84, 97, and 92%. Similar values were seen after limiting controls to those with only reflux or dysphagia or to those with esophageal eosinophilia not due to EoE. CONCLUSIONS: We validated a set of clinical and endoscopic features to predict EoE with a high degree of accuracy and allow identification of those at very low risk of disease. Use of these predictors at the point-of-care will avoid the effort and expense of low-yield histological examinations for EoE.

Recurrent intestinal metaplasia after radiofrequency ablation for Barrett's esophagus: endoscopic findings and anatomic location.

BACKGROUND: Radiofrequency ablation (RFA) is a safe and effective treatment for Barrett's esophagus (BE) that results in high rates of complete eradication of intestinal metaplasia (CEIM). However, recurrence is common after CEIM, and surveillance endoscopy is recommended. Neither the anatomic location nor the endoscopic appearance of these recurrences is well-described. OBJECTIVE: Describe the location of histologic specimens positive for recurrence after CEIM and the testing performance of endoscopic findings for the histopathologic detection of recurrence. DESIGN: Retrospective cohort. SETTING: Single referral center. PATIENTS: A total of 198 patients with BE with at least 2 surveillance endoscopies after CEIM. INTERVENTIONS: RFA, EMR, surveillance endoscopy. MAIN OUTCOME MEASUREMENTS: The anatomic location and histologic grade of recurrence. RESULTS: In a mean 3.0 years of follow-up, 32 (16.2%; 95% confidence interval [CI], 11.0%-22.0%) patients had recurrence of disease, 5 (2.5%; 95% CI, 0.3%-4.7%) of whom progressed beyond their worst before-treatment histology. Recurrence was most common at or near the gastroesophageal junction (GEJ). Recurrence>1 cm proximal to the GEJ always was accompanied by endoscopic findings, and random biopsies in these areas detected no additional cases. The sensitivity of any esophageal sign under high-definition white light or narrow-band imaging for recurrence was 59.4% (42.4%, 76.4%), and the specificity was 80.6% (77.2%, 84.0%). LIMITATIONS: Single-center study. CONCLUSION: Recurrent intestinal metaplasia often is not visible to the endoscopist and is most common near the GEJ. Random biopsies>1 cm above the GEJ had no yield for recurrence. In addition to biopsy of prior EMR sites and of suspicious lesions, random biopsies oversampling the GEJ are recommended.

Sex and race and/or ethnicity differences in patients undergoing radiofrequency ablation for Barrett's esophagus: results from the U.S. RFA Registry.

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.

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 Barrett's 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.

Viscous topical is more effective than nebulized steroid therapy for patients with eosinophilic esophagitis.

We performed a randomized trial to compare nebulized and viscous topical corticosteroid treatments for eosinophilic esophagitis (EoE). Subjects with incident EoE (n = 25) received budesonide 1 mg twice daily, either nebulized and then swallowed (NEB) or as an oral viscous slurry (OVB), for 8 weeks. Baseline eosinophil counts for the NEB and OVB groups were 101 and 83 (P = .62). Posttreatment counts were 89 and 11 (P = .02). The mucosal medication contact time, measured by scintigraphy, was higher for the OVB group than the NEB group (P < .005) and was inversely correlated with eosinophil count (R = -0.67; P = .001). OVB was more effective than NEB in reducing numbers of esophageal eosinophils in patients with EoE. OVB provided a significantly higher level of esophageal exposure to the therapeutic agent, which correlated with lower eosinophil counts.

Clinical and endoscopic characteristics do not reliably differentiate PPI-responsive esophageal eosinophilia and eosinophilic esophagitis in patients undergoing upper endoscopy: a prospective cohort study.

OBJECTIVES: Proton-pump inhibitor-responsive esophageal eosinophilia (PPI-REE) is a newly recognized entity that must be differentiated from eosinophilic esophagitis (EoE). Little is known about this condition. We aimed to determine the prevalence of PPI-REE and EoE in patients undergoing upper endoscopy and determine features that distinguish the two groups. METHODS: This prospective study conducted at the University of North Carolina from 2009 to 2011 enrolled consecutive adult patients undergoing outpatient upper endoscopy. Subjects had esophageal biopsies to quantify the maximum eosinophil count per high-power field (eos/hpf; hpf=0.24 mm(2)). If biopsies revealed ≥15 eos/hpf, subjects were treated with twice daily PPI for 8 weeks and endoscopy was repeated. If ≥15 eos/hpf persisted despite PPI therapy, EoE was diagnosed. If there were <15 eos/hpf, PPI-REE was diagnosed. The proportion of patients in each group was calculated, and patients with EoE and PPI-REE were compared. RESULTS: Of the 223 subjects enrolled, 173 had dysphagia and 50 did not. Of those with dysphagia, 66 (38%) had ≥15 eos/hpf. After the PPI trial, 40 (23%) were confirmed to have EoE, and 24 (14%) had PPI-REE. Of those without dysphagia, 2 (4%) had ≥15 eos/hpf, and after the PPI trial, 1 (2%) had EoE. Compared with EoE, PPI-REE patients were more likely to be older and male and less likely to have typical endoscopic findings of EoE. However, none of the individual factors was independently predictive of PPI-REE status on multivariable analysis. Similarly, although some endoscopic findings were differentially distributed between PPI-REE and EoE, none were significantly associated with disease status on multivariable analysis. CONCLUSIONS: Esophageal eosinophilia is common among patients undergoing esophagogastroduodenoscopy for dysphagia. Although EoE was seen in nearly a quarter of patients with dysphagia, PPI-REE was almost as common, and accounted for over one-third of those with ≥15 eos/hpf. No clinical or endoscopic features independently distinguished PPI-REE from EoE before the PPI trial.

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

OBJECTIVES: Radiofrequency ablation (RFA) of Barrett's 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.

Radiofrequency ablation in Barrett's esophagus with dysplasia.

BACKGROUND: Barrett's esophagus, a condition of intestinal metaplasia of the esophagus, is associated with an increased risk of esophageal adenocarcinoma. We assessed whether endoscopic radiofrequency ablation could eradicate dysplastic Barrett's esophagus and decrease the rate of neoplastic progression. METHODS: In a multicenter, sham-controlled trial, we randomly assigned 127 patients with dysplastic Barrett's esophagus in a 2:1 ratio to receive either radiofrequency ablation (ablation group) or a sham procedure (control group). Randomization was stratified according to the grade of dysplasia and the length of Barrett's esophagus. Primary outcomes at 12 months included the complete eradication of dysplasia and intestinal metaplasia. RESULTS: In the intention-to-treat analyses, among patients with low-grade dysplasia, complete eradication of dysplasia occurred in 90.5% of those in the ablation group, as compared with 22.7% of those in the control group (P<0.001). Among patients with high-grade dysplasia, complete eradication occurred in 81.0% of those in the ablation group, as compared with 19.0% of those in the control group (P<0.001). Overall, 77.4% of patients in the ablation group had complete eradication of intestinal metaplasia, as compared with 2.3% of those in the control group (P<0.001). Patients in the ablation group had less disease progression (3.6% vs. 16.3%, P=0.03) and fewer cancers (1.2% vs. 9.3%, P=0.045). Patients reported having more chest pain after the ablation procedure than after the sham procedure. In the ablation group, one patient had upper gastrointestinal hemorrhage, and five patients (6.0%) had esophageal stricture. CONCLUSIONS: In patients with dysplastic Barrett's esophagus, radiofrequency ablation was associated with a high rate of complete eradication of both dysplasia and intestinal metaplasia and a reduced risk of disease progression. (ClinicalTrials.gov number, NCT00282672.)

Detection of dysplasia in Barrett's esophagus with in vivo depth-resolved nuclear morphology measurements.

BACKGROUND & AIMS: Patients with Barrett's esophagus (BE) show increased risk of developing esophageal adenocarcinoma and are routinely examined using upper endoscopy with biopsy to detect neoplastic changes. Angle-resolved low coherence interferometry (a/LCI) uses in vivo depth-resolved nuclear morphology measurements to detect dysplasia. We assessed the clinical utility of a/LCI in the endoscopic surveillance of patients with BE. METHODS: Consecutive patients undergoing routine surveillance upper endoscopy for BE were recruited at 2 endoscopy centers. A novel, endoscope-compatible a/LCI system measured the mean diameter and refractive index of cell nuclei in esophageal epithelium at 172 biopsy sites in 46 patients. At each site, an a/LCI measurement was correlated with a concurrent endoscopic biopsy specimen. Each biopsy specimen was assessed histologically and classified as normal, nondysplastic BE, indeterminate for dysplasia, low-grade dysplasia (LGD), or high-grade dysplasia (HGD). The a/LCI data from multiple depths were analyzed to evaluate its ability to differentiate dysplastic from nondysplastic tissue. RESULTS: Pathology characterized 5 of the scanned sites as HGD, 8 as LGD, 75 as nondysplastic BE, 70 as normal tissue types, and 14 as indeterminate for dysplasia. The a/LCI nuclear size measurements separated dysplastic from nondysplastic tissue at a statistically significant (P < .001) level for the tissue segment 200 to 300 µm beneath the surface with an accuracy of 86% (147/172). A receiver operator characteristic analysis indicated an area under the curve of 0.91, and an optimized decision point gave 100% (13/13) sensitivity and 84% (134/159) specificity. CONCLUSIONS: These preliminary data suggest a/LCI is accurate in detecting dysplasia in vivo in patients with BE.

Durability of radiofrequency ablation in Barrett's esophagus with dysplasia.

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.

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 Barrett's 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.

A novel balloon pull-through technique for esophageal dilation in eosinophilic esophagitis (with video).

BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic inflammatory condition that can be complicated by esophageal strictures requiring endoscopic dilation. Whereas recent data have advanced the notion that dilation can be done effectively with minimal morbidity, issues concerning safety and tolerability remain. OBJECTIVE: To review our initial experience with a novel esophageal balloon pull-through technique for sizing and dilation in EoE as well as to present a video illustrating the methodology. DESIGN: Case series. SETTING: Tertiary-care referral center. PATIENTS: Thirteen patients with EoE. INTERVENTION: Balloon pull-through technique for esophageal dilation. MAIN OUTCOME MEASUREMENTS: Dilation effect, size, and complications (esophageal perforation, bleeding requiring endoscopic hemostasis, or severe chest pain requiring hospitalization). RESULTS: Thirteen patients (7 men, 6 women; mean age 40 years, range 19-66 years) with EoE underwent dilation with the esophageal balloon pull-through technique. Resistance during the pull-through was encountered in 11 patients (85%), even though no discrete areas of narrowing were encountered. A tear was achieved in 9 patients (69%). Nine patients (69%) reported improvement in their dysphagia after dilation. There were no serious complications from the procedure. LIMITATIONS: Retrospective, single center, small patient numbers in this initial report. CONCLUSIONS: The esophageal balloon pull-through technique for esophageal dilation in patients with EoE appears to be safe and effective. It is a rational approach to gauging the luminal diameter of the esophagus and treating strictures in patients with EoE and dysphagia, but further prospective study is required to confirm these initial results.

A cost-utility analysis of ablative therapy for Barrett's esophagus.

BACKGROUND & AIMS: Recommendations for patients with Barrett's esophagus (BE) include endoscopic surveillance with esophagectomy for early-stage cancer, although new technologies to ablate dysplasia and metaplasia are available. This study compares the cost utility of ablation with that of endoscopic surveillance strategies. METHODS: A decision analysis model was created to examine a population of patients with BE (mean age 50), with separate analyses for patients with no dysplasia, low-grade dysplasia (LGD), or high-grade dysplasia (HGD). Strategies compared were no endoscopic surveillance; endoscopic surveillance with ablation for incident dysplasia; immediate ablation followed by endoscopic surveillance in all patients or limited to patients in whom metaplasia persisted; and esophagectomy. Ablation modalities modeled included radiofrequency, argon plasma coagulation, multipolar electrocoagulation, and photodynamic therapy. RESULTS: Endoscopic ablation for patients with HGD could increase life expectancy by 3 quality-adjusted years at an incremental cost of <$6,000 compared with no intervention. Patients with LGD or no dysplasia can also be optimally managed with ablation, but continued surveillance after eradication of metaplasia is expensive. If ablation permanently eradicates >or=28% of LGD or 40% of nondysplastic metaplasia, ablation would be preferred to surveillance. CONCLUSIONS: Endoscopic ablation could be the preferred strategy for managing patients with BE with HGD. Ablation might also be preferred in subjects with LGD or no dysplasia, but the cost effectiveness depends on the long-term effectiveness of ablation and whether surveillance endoscopy can be discontinued after successful ablation. As further postablation data become available, the optimal management strategy will be clarified.

Esophageal dilation in eosinophilic esophagitis: safety and predictors of clinical response and complications.

BACKGROUND: Esophageal strictures resulting from eosinophilic esophagitis present management challenges, and high rates of rents and perforation have been reported. OBJECTIVE: To assess the safety of esophageal dilation in eosinophilic esophagitis and to characterize predictors of both clinical response and complications of the procedure. DESIGN: Retrospective study of the University of North Carolina eosinophilic esophagitis database. SETTING: Tertiary care referral center. PATIENTS: Cases of eosinophilic esophagitis were defined as per consensus guidelines. INTERVENTION: Dilation with either Savary or through-the-scope balloon techniques. MAIN OUTCOME MEASUREMENTS: Complications (deep mucosal rents, contained or free perforation, and chest pain requiring medical attention or hospitalization) and the global clinical symptom response. RESULTS: Of 130 eosinophilic esophagitis cases identified, 70 dilations (12 Savary, 58 balloon) were performed in 36 patients. Esophageal size improved from 12 to 16 mm (P < .001), with an overall symptom response rate of 83%. The only predictor of clinical response was final dilation diameter. There were 5 complications (7%): 2 deep mucosal rents and 3 episodes of chest pain. There were no perforations. There was one hospitalization for chest pain. All complications occurred in patients being treated with topical steroids, who underwent balloon dilation. Complications were associated with younger age (23 vs 42; P = .02) and more dilations (4 vs 1.7; P = .009). LIMITATIONS: Single center, retrospective study. CONCLUSIONS: Esophageal dilation can be performed in eosinophilic esophagitis with low rates of tears, chest pain, and hospitalization. No perforations were found in our database. The effectiveness of dilation was best when a larger esophageal caliber was achieved, but patients undergoing more procedures was associated with complications.