Effects of Central Obesity on Esophageal Epithelial Barrier Function.

INTRODUCTION: We assessed if obesity perturbs the esophageal epithelial barrier function independent of promotion of gastroesophageal reflux (GER). METHODS: Thirty-eight participants were divided into 4 groups: Obesity-/GER-, Obesity+/GER-, Obesity-/GER+, and Obesity+/GER+. Esophageal intercellular space and desmosome density (structural integrity) and fluorescein leak (functional integrity) were measured. RESULTS: The Obesity+/GER- group demonstrated increased intercellular space, reduced desmosome density, and increased fluorescein leak compared with control subjects. These changes were similar but not additive to findings seen in Obesity-/GER + and Obesity+/GER+ patients. DISCUSSION: Central obesity impairs structural and functional integrity of the esophageal barrier independent of GER, likely predisposing to esophageal injury.

Development and Pilot Testing of Decision Aid for Shared Decision Making in Barrett's Esophagus With Low-Grade Dysplasia.

GOALS: To develop an encounter decision aid [Barrett's esophagus Choice (BE-Choice)] for patients and clinicians to engage in shared decision making (SDM) for management of BE with low-grade dysplasia (BE-LGD) and assess its impact on patient-important outcomes. BACKGROUND: Currently, there are 2 strategies for management of BE-LGD-endoscopic surveillance and ablation. SDM can help patients decide on their preferred management option. STUDY: Phase-I: Patients and clinicians were engaged in a user-centered design approach to develop BE-Choice. Phase-I included review of evidence on BE-LGD management, observation of usual care (UC), creation, field-testing, and iterative development of BE-Choice in clinical settings. Phase-II: Impact of BE-Choice on patient-important outcomes (patient knowledge, decisional conflict, and patient involvement in decision making) was assessed using a controlled before-after study design (UC vs. BE-Choice). RESULTS: Phase-I: Initial prototype was designed with observation of 8 clinical encounters. With field-testing, 3 successive iterations were made before finalizing BE-Choice. BE-Choice was paper based and fulfilled the qualifying criteria of International patient decision aid standards. Phase II: 29 patients were enrolled, 8 to UC and 21 to BE-Choice. Compared with UC, use of BE-Choice improved patient knowledge (90.4% vs. 70.5%; P=0.03), decisional comfort (89.6 vs. 71.9; P=0.01), and patient involvement (OPTION score: 27.1 vs. 19.2; P=0.01). CONCLUSIONS: BE-Choice is a feasible and effective decision aid to promote SDM in the management of BE-LGD. On pilot testing, BE-Choice had promising impact on patient-important outcomes. A larger multicenter trial is needed to confirm our results and promote widespread use of BE-Choice.

Outcomes of patients with submucosal (T1b) esophageal adenocarcinoma: a multicenter cohort study.

BACKGROUND AND AIMS: The treatment of submucosal (T1b) esophageal adenocarcinoma (EAC) remains in evolution, with some evidence supporting endoscopic management of low-risk lesions. Using a multicenter cohort, we evaluated outcomes of patients with T1b EAC and predictors of survival. METHODS: Patients diagnosed between 2001 and 2016 with T1b EAC were identified from 3 academic medical centers in the United States. Demographic, clinical, and outcome data were collected. Outcomes studied were overall and cancer-free survival. Cox proportional hazards models were constructed to assess independent predictors of survival. RESULTS: One hundred forty-one patients were included, of whom 68 (48%) underwent esophagectomy and 73 (52%) were treated endoscopically. Most patients (85.8%) had high-risk histologic features. Thirty-day operative mortality was 2.9%. Median follow-up in the esophagectomy and endoscopic cohorts was 49.4 and 43.4 months, respectively. Patients treated endoscopically were older with higher comorbidity scores, with 46 (63%) achieving histologic remission. Nineteen patients (26.0%) also received chemoradiation. Five-year overall survival rates in the surgical and endoscopic cohorts were 89% and 59%, respectively, whereas 5-year cancer-free survival rates were 92% and 69%. Presence of high-risk histologic features was associated with reduced overall survival. CONCLUSIONS: In this large multicenter study of patients with T1b EAC, esophagectomy was associated with improved overall but not cancer-free survival. High-risk histologic features were associated with poorer survival.

Comparative Assessment of Patient Preferences and Tolerability in Barrett Esophagus Screening: Results From a Randomized Trial.

GOALS: To determine patient preference for the Barrett esophagus (BE) screening techniques. BACKGROUND: Sedated esophagogastroduodenoscopy (sEGD) and unsedated transnasal endoscopy (uTNE) are both potential techniques for BE screening. However, systematic assessment of patient preference for these 2 techniques is lacking. As part of a comparative effectiveness randomized trial of BE screening modalities, we measured short-term patient preferences for the following approaches: in-clinic uTNE (huTNE), mobile-based uTNE (muTNE), and sEGD using a novel assessment instrument. STUDY: Consenting community patients without known BE were randomly assigned to receive huTNE, muTNE, or sEGD, followed by a telephone administered preference and tolerability assessment instrument 24 hours after study procedures. Patient preference was measured by the waiting trade-off method. RESULTS: In total, 201 patients completed screening with huTNE (n=71), muTNE (n=71), or sEGD (n=59), and a telephone interview. Patients' preferences for sEGD and uTNE using the waiting trade-off method were comparable (P=0.51). Although tolerability scores were superior for sEGD (P<0.001) compared with uTNE, scores for uTNE examinations were acceptable. CONCLUSIONS: Patient preference is comparable between sEGD and uTNE for diagnostic examinations conducted in an endoscopy suite or in a mobile setting. Given acceptable tolerability, uTNE may be a viable alternative to sEGD for BE screening.

The Esophageal Epithelial Barrier in Health and Disease.

Dysfunction in the esophageal epithelial barrier function is a major source for morbidity. To better understand the pathophysiologic pathways of the diseases associated with barrier dysfunction, including gastroesophageal reflux disease, eosinophilic esophagitis, Barrett's esophagus, and obesity, it is important to understand the esophageal epithelial embryologic development, microscopic anatomy with a special focus on the barrier structure and function, extraepithelial defense mechanisms, and how these change in the diseased state. In recent years, significant progress has been made in elucidating the esophageal barrier structure and function both in vitro and in vivo. This has enhanced the understanding of mechanisms of disease, and may also allow identification of therapeutic targets that can help in the management of these diseases. This review provides a detailed discussion regarding the esophageal epithelial barrier structure and function, the current and historical techniques used to study the barrier, and how it is affected by common esophageal diseases.

Costs associated with Barrett's esophagus screening in the community: an economic analysis of a prospective randomized controlled trial of sedated versus hospital unsedated versus mobile community unsedated endoscopy.

BACKGROUND AND AIMS: Data on the economic impact associated with screening for Barrett's esophagus (BE) are limited. As part of a comparative effectiveness randomized trial of unsedated transnasal endoscopy (uTNE) and sedated EGD (sEGD), we assessed costs associated with BE screening. METHODS: Patients were randomly allocated to 3 techniques: sEGD or uTNE in a hospital setting (huTNE) versus uTNE in a mobile research van (muTNE). Patients were called 1 and 30 days after screening to assess loss of work (because of the screening procedure) and medical care sought after procedure. Direct medical costs were extracted from billing claims databases. Indirect costs (loss of work for subject and caregiver) were estimated using patient reported data. Statistical analyses including multivariable analysis accounting for comorbidities were conducted to compare costs. RESULTS: Two hundred nine patients were screened (61 sEGD, 72 huTNE, and 76 muTNE). Thirty-day direct medical costs and indirect costs were significantly higher in the sEGD than the huTNE and muTNE groups. Total costs (direct medical + indirect costs) were also significantly higher in the sEGD than in the uTNE group. The muTNE group had significantly lower costs than the huTNE group. Adjustment for age, sex, and comorbidities on multivariable analysis did not change this conclusion. CONCLUSIONS: Short-term direct, indirect, and total costs of screening are significantly lower with uTNE compared with sEGD. Mobile uTNE costs were lower than huTNE costs, raising the possibility of mobile screening as a novel method of screening for BE and esophageal adenocarcinoma.

Who Deserves Endoscopic Screening for Esophageal Neoplasia?

Despite the availability of safe and effective endoscopic treatment of Barrett's esophagus (BE)-related dysplasia and neoplasia, the incidence and mortality from esophageal adenocarcinoma (EAC) have continued to increase. This likely stems from the large population of patients that develop EAC outside of a BE screening and surveillance program. Identification of BE with screening followed by enrollment in an appropriate surveillance/risk stratification program could be a strategy to address both the incidence of and mortality from EAC. This article summarizes the rationale and challenges for BE screening, the risk factors for BE, and the currently described BE risk assessment tools.

Influence of reflux and central obesity on intercellular space diameter of esophageal squamous epithelium.

BACKGROUND: While central obesity increases gastroesophageal reflux (GER) by mechanically disrupting the anti-reflux barrier, limited data exist on pathways by which central obesity may potentiate esophageal injury by non-mechanical means. Obesity has been associated with an impaired epithelial intestinal barrier. OBJECTIVE: We aimed to assess the influence of central obesity and reflux on the squamous esophageal epithelial intercellular space diameter (ICSD). METHODS: The ICSD was measured using electron microscopy in esophageal biopsies from individuals who underwent ambulatory pH monitoring and endoscopy. Anthropometric measurements were obtained on all participants. Participants were classified into four groups: with and without central obesity and reflux. RESULTS: Sixteen individuals were studied with four in each study group. The mean ICSD was almost three-fold greater (p < 0.001) in the group with central obesity without reflux, compared to controls without central obesity and reflux. It was also comparable to the ICSD in groups with acid reflux only and those with both reflux and central obesity. CONCLUSIONS: There is evidence of esophageal squamous ICSD increase in individuals with central obesity who do not have evidence of acid and nonacid reflux on ambulatory pH monitoring. This may reflect a mechanism by which central obesity potentiates reflux-induced esophageal injury and inflammation.

Endoscopic therapy for Barrett's oesophagus.

Barrett's oesophagus (BO) is thought to progress through the development of dysplasia (low grade and high grade) to oesophageal adenocarcinoma, a lethal cancer with poor survival. The overall goal of endoscopic therapy of BO is to eliminate metaplastic and dysplastic epithelium, to prevent and/or reduce the risk of progression to OAC. Endoscopic therapy techniques can be divided into two broad complementary techniques: tissue acquiring (endoscopic mucosal resection and endoscopic submucosal dissection) and ablative. Endoscopic therapy has been established as safe and effective for the subjects with intra-mucosal cancer (IMC), high-grade dysplasia (HGD) and more recently in treating low-grade dysplasia (LGD). Challenges to endoscopic therapy are being recognized, such as incomplete response and recurrence. While eradication of intestinal metaplasia is the immediate goal of endoscopic therapy, surveillance must continue after complete elimination of intestinal metaplasia, to detect and treat recurrences.