Virological and immunological responses to raltegravir and dolutegravir in the gut-associated lymphoid tissue of HIV-infected men and women.

BACKGROUND: Raltegravir (RTG) and dolutegravir (DTG) have different pharmacokinetic patterns in the gastrointestinal tract. To determine if this results in pharmacodynamic differences, we compared HIV RNA, HIV DNA and immunological markers in gut-associated lymphoid tissue (GALT) of HIV-infected participants receiving RTG or DTG with tenofovir+emtricitabine (TDF/FTC). METHODS: GALT specimens from the terminal ileum, splenic flexure and rectum were obtained by colonoscopy at a single time point in 20 adults treated with RTG (n=10) or DTG (n=10) with HIV RNA <50 copies/ml. Flow cytometry, drug concentrations, and HIV RNA and DNA were analysed in tissue. CD4/8+ T-cells were tested for γδ TCR, and markers of T-cell activation and exhaustion. Data are reported as median (Q1-Q3). RESULTS: A total of 15 men and 5 women were enrolled. There was no difference in time since HIV diagnosis for those on RTG (9.5 [4-22] years) and DTG (17 [1-24] years; P=0.6), although time on RTG (5.4 [2.3-6.7] years) was greater than DTG (1.0 [0.1-1.5] years; P<0.001). Concentrations of RTG and DTG in rectal tissue were similar to previous reports: median tissue:plasma ratio was 11.25 for RTG and 0.44 for DTG. RNA:DNA ratios were 1.14 (0.18-5.10) for the RTG group and 0.90 (0.30-18.87) for the DTG group (P=0.95). No differences (P≥0.1) between CD4+ and CD8+ T-cell markers were found. CONCLUSIONS: RTG produced higher tissue exposures than DTG, but no significant differences in GALT HIV RNA, DNA or most immunological markers were observed. ClinicalTrials.gov NCT02218320.

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.

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.

Cervicovaginal and Rectal Fluid as a Surrogate Marker of Antiretroviral Tissue Concentration: Implications for Clinical Trial Design.

BACKGROUND: Quantifying tissue drug concentrations can yield important information during drug development, but complicates pharmacokinetic study design. Mucosal fluids collected by direct aspiration (cervicovaginal fluid; CVF) or swab (rectal fluid; RF) might be used as tissue concentration surrogates, but these relationships are not well characterized. METHODS: Forty-nine healthy women, given a single oral dose of tenofovir, maraviroc, emtricitabine, or raltegravir at 50%-200% of the treatment dose, provided 13 plasma, 12 CVF, 12 RF and one cervical, vaginal and rectal tissue biopsy over 48 hours. Relationships between these paired samples were characterized by linear and multiple linear regression. Adjusted r values were used to select the final predictive models. RESULTS: CVF exposure increased linearly with dose for all antiretrovirals (r(2) ≥ 0.23, P ≤ 0.02) except raltegravir (r(2) = 0.08, P = 0.19). In RF, only emtricitabine increased linearly with dose (r(2) = 0.27, P = 0.01). For all antiretrovirals, CVF and RF concentrations significantly correlated with mucosal tissue concentrations (female genital tract r(2) ≥ 0.37, rectal tissue (2)r ≥ 0.50, P ≤ 0.001). In the final multivariate models, plasma and fluid concentrations were both associated with FGT concentrations for all antiretrovirals (r(2) ≥ 0.81, P < 0.001). The same was noted for rectal tissue (r(2) ≥ 0.58, P < 0.001) except for tenofovir, for which RF alone was predictive of tissue concentration (r(2) = 0.91, P < 0.001). CONCLUSIONS: Mucosal fluids were positively correlated with tissue concentrations and including plasma concentrations improved the regression models in most cases. Dose linearity in CVF, but not RF, suggests a saturation process in lower gastrointestinal tract tissue. These findings suggest that mucosal fluid and plasma concentrations may be used for qualitative inference of tissue concentrations for these antiretrovirals.

Advanced Esophageal Squamous Cell Dysplasia and Early Carcinoma Detected After Remote Esophagectomy for Adenocarcinoma.

We present a case of squamous dysplasia and early squamous carcinoma of the esophagus after esophagectomy for esophageal adenocarcinoma. We briefly discuss mucosectomy and ablative therapy as potential treatment options.

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.

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.

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.

Extraesophageal presentations of GERD: where is the science?

This article reviews the evaluation and management of patients with suspected extraesophageal manifestations of gastroesophageal reflux disease, such as asthma, chronic cough, and laryngitis, which are commonly encountered in gastroenterology practices. Otolaryngologists and gastroenterologists commonly disagree upon the underlying cause for complaints in patients with one of the suspected extraesophageal reflux syndromes. The accuracy of diagnostic tests (laryngoscopy, endoscopy, and pH- or pH-impedance monitoring) for patients with suspected extraesophageal manifestations of gastroesophageal reflux disease is suboptimal. An empiric trial of proton pump inhibitors in patients without alarm features can help some patients, but the response to therapy is variable.

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.

Differential penetration of raltegravir throughout gastrointestinal tissue: implications for eradication and cure.

OBJECTIVE: To investigate the concentration of the integrase strand inhibitor raltegravir (RAL) throughout gastrointestinal (GI) tissue, especially gut-associated lymphoid tissue (GALT), as an adjunct to current prevention and cure strategies. DESIGN: Open-label pharmacokinetic (PK) study. METHODS: HIV-negative men received RAL 400 mg twice daily for 7 days. Seven blood plasma specimens were collected over 12-h intervals; timed tissue specimens from terminal ileum, splenic flexure, and rectum were also obtained by colonoscopy following the first dose and on day 7 [multiple dose (MD)]. RAL concentrations were measured by validated LC-MS assay with 1 ng/ml lower limit of detection. Data were analyzed by noncompartmental methods (WinNonlin 6). Tissue exposures are reported as composite medians and tissue density of 1.04 g/ml is assumed for comparisons. RESULTS: Fourteen men completed evaluations. Median (range) age was 24 (19-49) years and BMI 25 (19-31) kg/m². After the first dose, area under the time-concentration curve (AUC)(0-12h) was highest in the terminal ileum (594 µg*h/ml). Exposures were 160, 68 and 39-fold greater than blood plasma at the terminal ileum, splenic flexure and rectum, respectively. After multiple doses, exposure was highest at the splenic flexure (2240 µg*h/ml); exposure at the terminal ileum and rectum were equivalent (both 788 µg*h/ml). Following multiple doses, exposures were 160 to 650-fold greater than blood plasma throughout the colon. CONCLUSION: RAL rapidly disseminates into GI tissue and concentrations remain significantly higher than blood plasma. RAL exposure in GI tissue remains higher than any antiretroviral investigated to date. These data suggest that RAL should result in full suppression of viral replication in GI tissue and GALT.

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.

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.

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.

Antireflux surgery in the proton pump inhibitor era.

Although proton pump inhibitors (PPIs) are now the first-line treatment for gastroesophageal reflux disease (GERD), surgery still has several specific indications. We review the current treatment of GERD and discuss how antireflux surgery fits into the overall scheme.

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.

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.

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.

Outcomes of a combined antegrade and retrograde approach for dilatation of radiation-induced esophageal strictures (with video).

BACKGROUND: Treatment of head, neck, and esophageal cancers with radiation therapy can lead to esophageal strictures. In some cases, these can progress to complete esophageal obstruction, precluding typical antegrade endoscopic dilation. OBJECTIVE: The aim of this study was to review our experience with a combined antegrade/retrograde technique for dilation of complete esophageal strictures. DESIGN: Case series. SETTING: Tertiary-care referral center. PATIENTS: Twelve patients with complete esophageal radiation-induced strictures. INTERVENTIONS: In collaboration with otolaryngologists who performed direct antegrade esophagoscopy, retrograde endoscopy via gastrostomy was simultaneously performed. While visualizing the stricture from both sides and transilluminating, it was recannulated with use of a biliary or spring-tipped guidewire, and then dilated. MAIN OUTCOME MEASUREMENTS: Dilation method, complications, and postdilation oral intake. RESULTS: Combined antegrade and retrograde dilation was technically possible in 10 of the 12 patients (83%). Two cases were unsuccessful due to an inability to achieve transillumination. The only significant complication was a contained esophageal perforation that was managed nonoperatively. The mean number of repeat dilations was 7 (range, 1-22); none were complicated by perforation. Esophageal patency allowing at least some oral intake and tolerance of secretions was ultimately successful in 8 patients (67%). LIMITATIONS: Retrospective, single center. CONCLUSIONS: A combined antegrade/retrograde approach for dilation of complete esophageal radiation-induced strictures in collaboration with colleagues from otolaryngology is a viable treatment option. The procedure is technically feasible, effective, and well tolerated, although there may be an increased risk of esophageal perforation. This strategy may obviate a more invasive surgical approach.

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.