Blevins, Christopher H.

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.

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.

Abstract Background The neo-squamous epithelium that replaces columnar epithelium after successful endoscopic ablation of Barrett's esophagus (BE) has not been fully characterized in regard to its structural and functional integrity. Intercellular space is a surrogate marker for epithelial structural integrity and mucosal impedance (MI) is a surrogate for transepithelial resistance and thus epithelial functional integrity. Impairment of the structural and functional integrity may influence recurrence following successful ablation. We aimed to measure the esophageal epithelial intercellular space diameter and MI in the neo-squamous and normal squamous epithelium of patients who underwent successful radiofrequency ablation for dysplastic BE. Methods Forty patients with complete remission of intestinal metaplasia (CRIM) (defined as two negative surveillance endoscopies for intestinal metaplasia) were prospectively recruited. Patients were excluded if they had endoscopic evidence of esophagitis. MI measurements were taken at 1 cm above the GE junction and 2 cm above the prior BE segment (targeting uninvolved squamous epithelium), using a novel through the scope MI probe. Endoscopic biopsies were also taken at these corresponding sites to assess intercellular space diameter using transmission electron microscopy (TEM) using standard techniques. Results 80% of patients were male with a mean age of 69 years. Mean follow since achieving CRIM was 30 months. 39 patients underwent RFA for dysplasia. The mean intercellular space diameter was higher in the neo-squamous epithelium (1.01 μm) when compared to the untreated native squamous epithelium (0.96 μm) [Difference of 0.056 μm, 95% CI of -0.036 to 0.148, P = 0.228]. The mean MI was significantly lower in the neosquamous epithelium (4001.3 Ω) when compared to the untreated native epithelium (5168.1 Ω) [Difference of 1166.7 Ω, 95% CI 418.8 to 1914.6, P = 0.003]. Conclusion Neo-squamous epithelium that replaces BE epithelium following successful endoscopic therapy for BE appears to be functionally and likely structurally deficient with regards to acid reflux barrier function, when compared to native squamous esophageal epithelium. This impairment may be associated with recurrence following successful ablation. Disclosure All authors have declared no conflicts of interest.

AbstractBackgroundThe mechanism by which obesity leads to damage independent of reflux is unclear. We aimed to determine the influence of obesity on mean nocturnal baseline impedance (MNBI), a functional measure of the epithelial barrier, in the presence and absence of acid reflux, using ambulatory pH impedance measurements.MethodsTwenty‐four‐hour pH impedance studies performed off medications in Caucasian men with a normal endoscopic examination were assessed for level of acid exposure and MNBI. Four patient groups were studied: Group 1, Not obese and normal acid exposure; Group 2, Obese and normal acid exposure; Group 3, Not obese and increased acid exposure; and Group 4, Obese with increased acid exposure.ResultsOne hundred patients were studied (25 in each group). Mean esophageal mucosal impedance (MI) was substantially lower in obese patients without reflux (Group 2) and non‐obese patients with reflux (Group 3) compared to normal controls (non‐obese, no reflux, Group 1). MI was progressively lower in the distal (vs the proximal) esophagus in GER patients, compared to those without GER. This difference persisted in the presence or absence of obesity. In contrast, in obese patients, the mean MI was significantly lower throughout the esophagus when compared to the non‐obese patients and also persisted in the presence and absence of accompanying reflux. Obesity and reflux were both independently negatively correlated with MI.ConclusionObesity is associated with abnormal esophageal MNBI. In contrast to gastro‐esophageal reflux, this decrease is pan‐esophageal. These data may support a systemic mechanism by which obesity alters the esophageal barrier function.

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.

BackgroundWhile 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.ObjectiveWe aimed to assess the influence of central obesity and reflux on the squamous esophageal epithelial intercellular space diameter (ICSD).MethodsThe 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.ResultsSixteen 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.ConclusionsThere 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.