788 VARIABLE GEOGRAPHICAL DIFFERENCES OF AMBULATORY ESOPHAGEAL REFLUX MONITORING IN MEXICO

Ambulatory esophageal reflux monitoring (AEpH) is useful in evaluating persistent or refractory esophageal symptoms despite adequate pharmacologic and/or surgical therapy. There is limited information whether there are geographical or regional differences in the diagnostic outcome of this test. Aim Characterize the diagnostic outcome of AEpH in a diverse population of Mexico. Analyze whether there is regional geographical diagnostic variability. Methods Data was collected from four major referral centers representing diverse geographical areas of Mexico: Mexico City-Central (two centers, years 2016-2020), Veracruz-South (years 2015-2020) and Monterrey-North (years 2013-2020). Consecutive patients undergoing AEpH with persistent GERD symptoms despite PPI therapy and negative upper endoscopy (no erosive disease >C or D LA classification) were entered into a data base and analyzed. Patients were classified as: NERD (acid exposure time (AET > 6.0%); hypersensitive esophagus (normal AET and positive symptom index (SI) or positive symptom association probability [SAP]); functional heartburn (NL AET, neg SI/SAP). Statistics: ANOVA, Chi-square and descriptive methods were used to compare variables among groups. Results 969 cases met inclusion criteria: 311 (32.1%) Central, 430 (44.3%) South, and 228 (23.5%) North. The results are summarized in the table. There were more women 618(63.8%) than men 351(36.2%); p < 0.001 with a mean age 47.7 ± 14.3. Patients were older in Central-Mexico 49.3 ± 13.6 years vs South 47.5 ± 15 and North 46.1 ± 13.6; p = 0.033. Functional heartburn was the most common diagnosis overall and more prevalent in Central-Mexico 171(55%) vs North 97(42.5%) and South 160(37.2%); p < 0.001. NERD was more predominant in the South 171(39.8%) vs North 72(31.6%) and Central-Mexico 98(31.5%); p = 0.029. Hypersensitive esophagus was more frequent in the North 59(25.9%) vs South 99(23%), and Central 42(13.5%); p < 0.001. Conclusion This is the first large data base study to evaluate the outcome of ambulatory esophageal reflux pH testing in Mexico. Our findings indicate a geographical variability of GERD phenotypes and suggest that further investigations are warranted to determine the causes of this distribution.

Impaired Esophageal Mucosal Integrity and the Related Motility Factors in Refractory Gastroesophageal Reflux Disease

Backgrounds. Research on esophageal mucosal integrity in gastro-oesophageal reflux disease (GERD) has been taken seriously in recent years, especially in refractory GERD. Mean nocturnal baseline impedance (MNBI) is proposed as an indicator of impaired mucosal integrity. We aimed to compare the MNBI value and investigate the impact of esophageal motility on MNBI in different subtypes of refractory GERD. Methods. Endoscopy, high-resolution manometry, and 24h impedance-pH monitoring were performed in 412 refractory GERD patients. From these patients, 94 erosive esophagitis (EE), 52 non-erosive reflux disease (NERD), and 31 Barrett's esophagus (BE) patients were enrolled in the study. EE group 54 included Los Angeles (LA) Grade-A/B and 40 LA Grade-C/D patients. 52 functional heartburn (FH) patients were used as the control. MNBI was acquired at 3 and 5 cm above lower esophageal sphincter (LES) and was compared between groups. Parameters of esophagogastric junction (EGJ) and LES, along with esophageal peristaltic sequences were recorded. Univariate and multivariate regression analysis were performed to determine the impact of these motility factors on MNBI in different subtypes of refractory GERD. Results. MNBI values were signifiantly lower in all subgroups of refractory GERD patients than in FH patients. MNBI in NERD patients was similar with LA-A/B and LA-C/D patients. MNBI in NERD and LA-C/D patients was signifiantly lower than in BE patients. No difference in MNBI was found between LA-A/B and BE patients. Ineffective esophageal motility and absent contractility were the risk factor for decreased MNBI in LA-A/B and LA-C/D patients, respectively. Type III EGJ (hiatus hernias) and decreased LES length were the risk factor for decreased MNBI in NERD and BE patients, respectively. Conclusions. Impaired mucosal integrity of NERD patients was as severe as that of EE patients and hiatus hernias were the risk factor, therefore, mucosal protections and explorations of hiatus hernias should be emphasized in refractory NERD patients. Weakened esophageal body peristalsis and decreased LES length were the risk factor for the impaired mucosal integrity of refractory EE patients and BE patients, respectively, and thus the therapy on peristaltic disorders and LES function was recommended for them. These results provided new ideas for optimizing the treatment of refractory GERD.

Capsaicin-Sensitive Vagal Afferent Nerve-Mediated Interoceptive Signals in the Esophagus

Heartburn and non-cardiac chest pain are the predominant symptoms in many esophageal disorders, such as gastroesophageal reflux disease (GERD), non-erosive reflux disease (NERD), functional heartburn and chest pain, and eosinophilic esophagitis (EoE). At present, neuronal mechanisms underlying the process of interoceptive signals in the esophagus are still less clear. Noxious stimuli can activate a subpopulation of primary afferent neurons at their nerve terminals in the esophagus. The evoked action potentials are transmitted through both the spinal and vagal pathways to their central terminals, which synapse with the neurons in the central nervous system to induce esophageal nociception. Over the last few decades, progress has been made in our understanding on the peripheral and central neuronal mechanisms of esophageal nociception. In this review, we focus on the roles of capsaicin-sensitive vagal primary afferent nodose and jugular C-fiber neurons in processing nociceptive signals in the esophagus. We briefly compare their distinctive phenotypic features and functional responses to mechanical and chemical stimulations in the esophagus. Then, we summarize activation and/or sensitization effects of acid, inflammatory cells (eosinophils and mast cells), and mediators (ATP, 5-HT, bradykinin, adenosine, S1P) on these two nociceptive C-fiber subtypes. Lastly, we discuss the potential roles of capsaicin-sensitive esophageal afferent nerves in processing esophageal sensation and nociception. A better knowledge of the mechanism of nociceptive signal processes in primary afferent nerves in the esophagus will help to develop novel treatment approaches to relieve esophageal nociceptive symptoms, especially those that are refractory to proton pump inhibitors.

Objective Evidence of Gastro-Esophageal Reflux Disease is Rare in Patients with Autoimmune Gastritis

Background and Aims: Patients with autoimmune atrophic gastritis (AAG) often complain of acid reflux symptoms, despite the evidence of hypo-achlorhydria. Rome IV criteria are used to define functional esophageal disorders. Our aim was to characterize gastroesophageal reflux disease (GERD) phenotypes in patients with AAG. Methods: Between 2017-2018, 172 AAG patients were evaluated at Gastro-Oncology outpatient clinic of University of Padua. Of them, 38 patients with reflux symptoms underwent high-resolution manometry (HRM) and multichannel intraluminal impedance-pH monitoring (MII-pH). Seventy-six AAG consecutive patients asymptomatic for gastroesophageal reflux were selected as age and gender matched controls. Serum biomarkers (pepsinogens, gastrin-17 and Helicobacter pylori antibodies), upper endoscopy, histology and clinical data were compared. Results: Out of 38/172 (22%) AAG patients with reflux symptoms, 2/38 had a GERD diagnosis based on abnormal esophageal acid exposure and 6/38 had a major motility disorder (i.e. outflow obstruction). Among the 30/38 patients with normal endoscopic findings, 9/30 had reflux hypersensitivity, 19 functional heartburn, 1 functional globus, 1 functional chest pain according to the Rome IV criteria. Antral atrophy, advanced corpus atrophy and OLGA stage were more frequent in controls than in reflux patients (p=0.01, p=0.031, p=0.01, respectively). No differences were found for serum biomarkers and symptom presentation. Most of the patients received proton pump inhibitors (PPIs) treatment (87%), with a minority (34%) reporting clinical benefit. Conclusions: Reflux symptoms are relatively common in AAG patients, but a firm diagnosis of GERD is rare (5%), whereas most of the patients have a functional disorder. PPI treatment is mostly clinical ineffective and should not be largely indicated.

Diagnostic performance of salivary pepsin for gastroesophageal reflux disease

Summary Uncertain diagnostic performance has limited clinical adoption of salivary pepsin, a noninvasive diagnostic tool for gastroesophageal reflux disease (GERD). This study aimed to assess diagnostic performance of salivary pepsin, and test validity of thresholds in an external cohort of patients with or without GERD. This two-phase prospective study conducted at two centers enrolled adult asymptomatic volunteers, patients with symptoms of GERD undergoing reflux monitoring, and patients with Barrett’s esophagus (BE). Fasting saliva samples were processed for pepsin concentration using Peptest. Phase 1 compared pepsin concentration between No GERD (volunteers/functional heartburn) and GERD (erosive reflux disease/nonerosive reflux disease (NERD)/BE). Phase 2 tested validity of the diagnostic thresholds identified from Phase 1 among external functional heartburn and NERD cohorts. Of 243 enrolled subjects, 156 met inclusion criteria. Phase 1 (n = 114): Pepsin concentrations were significantly higher in GERD (n = 84) versus No GERD (n = 30) (73.8 ng/mL vs. 21.1 ng/mL; P < 0.001). Area under the curve for pepsin concentration was 0.74 (95% CI 0.65, 0.83). A salivary pepsin threshold of 24.9 ng/mL optimized the true negative rate and 100.0 ng/mL optimized the true positive rate. Phase 2 (n = 42): Pepsin concentrations were significantly higher in NERD (n = 22) versus Functional Heartburn (n = 20) (176.0 ng/mL vs. 53.3 ng/mL, P < 0.001). Applying Phase 1 thresholds in this external cohort, salivary pepsin 24.9 ng/mL was 86% sensitive (64%, 97%) and 100.0 ng/mL was 72% specific for distinguishing NERD from functional heartburn. Given modest sensitivity and specificity for GERD, salivary pepsin may have clinical utility as a noninvasive office based diagnostic screening tool for GERD.

Diagnostic predictors of effective therapy for gastroesophageal reflux disease

In Chelyabinsk from January 2020 the method of 24-hour pH-impedance-monitoring of the esophagus was introduced. The analysis of diagnostic possibilities of this research even on a small initial sample of patients confirms high informativeness of the method in the section of diseases of the upper parts of the gastrointestinal tract. The combination of parameters of daily recording of pH-impedanceograms allows reliable identification of gastroesophageal refl ux disease (GERD) and functional dyspepsia. The tasks of differentiating the nosological affiliation of symptoms (heartburn, burning, chest pain, lump in the throat, voice axis, cough) arise for doctors of different specialties: gastroenterologists, otolaryngologists, pulmonologists, cardiologists. Comparing the complaints noted by the patient with episodes of the bolus hitting the esophagus, we get the opportunity to calculate the probability of association of symptoms with refl uxes, and thus correctly route the “complex” patient.Thus, the daily pH-impedanceometry demonstrates high diagnostic capabilities and allows us to reliably distinguish the pathological gastroesophageal refl ux from functional heartburn. Conducting research at the stage of diagnosis and during treatment makes the technique an effective tool for quality control of the therapeutic solution in each clinical situation.