Measurement of low-grade inflammation of the esophageal mucosa with electrical conductivity shows promise in assessing PPI responsiveness in patients with GERD.

A device that can easily measure electrical impedance might be a helpful tool for investigating the pathophysiology of gastroesophageal reflux disease. The first aim of this study was to validate our newly developed bioelectrical admittance measurement (BAM) through in vitro experimentation. The second aim was to investigate whether evaluation of BAM by this measurement differed between patients with heartburn according to their response to proton pump inhibitor (PPI) therapy. Caco-2 cell monolayers and three-dimensional tissues were examined by BAM using a frequency response analyzer. BAM was also used to measure the impedance through cell layers. Subsequently, BAM was performed during endoscopy in 41 patients experiencing heartburn without esophageal mucosal breaks. After 2-wk administration of 20-mg rabeprazole twice daily, patient responses to PPI were classified as "good" or "poor" according to their clinical course. In each patient, histological alterations and gene expression levels of inflammation mediators and tight junction proteins were evaluated. Impedance profiles indicated that monolayer Caco-2 cells on top of eight-layered normal human dermal fibroblasts had the highest magnitude of impedance over the range of frequencies. In vivo results revealed that patients with good responses to PPI displayed significantly higher admittance. Severity of low-grade inflammation was significantly associated with esophageal wall admittance. Moreover, esophageal wall admittance may be more closely related to basal zone hyperplasia than dilatation of intercellular spaces. Thus, BAM may be able to detect abnormalities in the subepithelial layer of the esophagus.NEW & NOTEWORTHY Bioelectrical admittance measurement is a new method to evaluate esophageal mucosal permeability vertically during upper gastrointestinal endoscopy. Measurement of low-grade inflammation of the esophageal mucosa with electrical conductivity shows promise in assessing proton pump inhibitor responsiveness in patients with gastroesophageal reflux disease. As various gastrointestinal diseases are associated with changes in mucosal permeability, bioelectrical admittance measurement is expected to be clinically applied to therapeutic decision-making for these diseases in the future.

Conventional and simple methods of measuring esophageal nocturnal baseline impedance show excellent agreement.

OBJECTIVES: Mean nocturnal baseline impedance (MNBI) shows promise in investigating reflux disease by reflecting esophageal mucosal integrity. This study aimed to measure MNBI by both conventional and simple methods in patients with laryngopharyngeal reflux (LPR) and gastroesophageal reflux disease (GERD) in order to evaluate the efficacy of the simple measurement method. METHODS: Altogether 187 patients were divided into LPR (n = 105) or GERD (n = 82) groups according to their predominant symptom profile, and underwent off-therapy impedance-pH monitoring. MNBI was measured by both the conventional and simple methods. The Bland-Altman plots were constructed to assess mean differences and to identify bias in the two measurement methods. RESULTS: For the two measurement methods, mean difference was (-89 ± 328) Ω in the distal esophagus, (-6 ± 653) Ω in the proximal esophagus, and (128 ± 577) Ω in the pharynx, respectively. There was a strong correlation between conventional and simple MNBI values, with  the coefficient of 0.940 in the distal esophagus, 0.463 in the proximal esophagus, and 0.712 in the pharynx (all P < 0.001). CONCLUSIONS: There was an excellent agreement between the conventional and simple methods of MNBI measurement, with no evidence of proportional bias. Conventional and simple MNBI values correlated excellently in the distal esophagus and moderately well in the proximal esophagus and pharynx. This study supports the use of the simple method of measuring MNBI to enhance diagnoses of reflux disease.

Heartburn sensation in nonerosive reflux disease: pattern of superficial sensory nerves expressing TRPV1 and epithelial cells expressing ASIC3 receptors.

The underlying causes of heartburn, characteristic symptom of gastroesophageal reflux disease (GERD), remain incompletely understood. Superficial afferent innervation of the esophageal mucosa in nonerosive reflux disease (NERD) may drive nociceptive reflux perception, but its acid-sensing role has not yet been established. Transient receptor potential vanilloid subfamily member-1 (TRPV1), transient receptor potential melastatin 8 (TRPM8), and acid-sensing ion channel 3 (ASIC3) are regulators of sensory nerve activity and could be important reflux-sensing receptors within the esophageal mucosa. We characterized TRPV1, TRPM8, and ASIC3 expression in esophageal mucosa of patients with GERD. We studied 10 patients with NERD, 10 with erosive reflux disease (ERD), 7 with functional heartburn (FH), and 8 with Barrett's esophagus (BE). Biopsies obtained from the distal esophageal mucosa were costained with TRPV1, TRPM8, or ASIC3, and CGRP, CD45, or E-cadherin. RNA expression of TRPV1, TRPM8, and ASIC3 was assessed using qPCR. Patients with NERD had significantly increased expression of TRPV1 on superficial sensory nerves compared with ERD (P = 0.028) or BE (P = 0.017). Deep intrapapillary nerve endings did not express TRPV1 in all phenotypes studied. ASIC3 was exclusively expressed on epithelial cells most significantly in patients with NERD and ERD (P ≤0.0001). TRPM8 was expressed on submucosal CD45+ leukocytes. Superficial localization of TRPV1-immunoreactive nerves in NERD, and increased ASIC3 coexpression on epithelial cells in NERD and ERD, suggests a mechanism for heartburn sensation. Esophageal epithelial cells may play a sensory role in acid reflux perception and act interdependently with TRPV1-expressing mucosal nerves to augment hypersensitivity in patients with NERD, raising the enticing possibility of topical antagonists for these ion channels as a therapeutic option.NEW & NOTEWORTHY We demonstrate for the first time that increased pain perception in patients with nonerosive reflux disease likely results from expression of acid-sensitive channels on superficial mucosal afferents and esophageal epithelial cells, raising the potential for topical therapy.

Mucosal pathogenesis in gastro-esophageal reflux disease.

BACKGROUND: Despite gastro-esophageal reflux disease affecting up to 20% of Western populations, relatively little is known about the molecular mechanisms underlying its most troublesome symptom: heartburn. Recent findings have unveiled the role of components of the esophageal mucosa in the pathogenesis of GERD including sensory nociceptive nerves and inflammatory mediators. Erosive esophagitis was long believed to develop as a result of acid injury at the esophageal lumen, but novel concepts suggest the generation of reflux-induced esophageal injury as a result of cytokine-mediated inflammation. Moreover, the localization and characterization of mucosal afferent nerves vary between GERD phenotypes and could explain the heterogeneity of symptom perception between patients who experience similar levels of acid reflux. PURPOSE: The purpose of this review is to consider the crosstalk of different factors of the esophageal mucosa in the pathogenesis of GERD, with a particular focus on mucosal innervation and molecular basis of acid-induced cytokine response. We discuss the current understanding of the mucosal response to acid injury, the nociceptive role of acid-sensitive receptors expressed in the esophageal mucosa, and the role of esophageal epithelial cells in initiating the onset of erosive esophagitis.

The esophageal mucosal barrier in health and disease: mucosal pathophysiology and protective mechanisms.

Diseases of the esophagus, such as gastroesophageal reflux (GER), can result in changes to mucosal integrity, neurological function, and the microbiome. Although poorly understood, both age and GER can lead to changes to the enteric nervous system. In addition, the esophagus has a distinct microbiome that can be altered in GER. Mucosal integrity is also at risk due to persistent damage from acid. Diagnostic tools, such as ambulatory pH/impedance testing and esophageal mucosal impedance, can assess short-term and longitudinal GER burden, which can also assess the risk for mucosal compromise. The quality of the mucosal barrier is determined by its intercellular spaces, tight junctions, and tight junction proteins, which are represented by claudins, occludins, and adhesion molecules. Fortunately, there are protective factors for mucosal integrity that are secreted by the esophageal submucosal mucous glands and within saliva that are augmented by mastication. These protective factors have potential as therapeutic targets for GER. In this article, we aim to review diagnostic tools used to predict mucosal integrity, aging, and microbiome changes to the esophagus and esophageal mucosal defense mechanisms.

Esophageal physiology-an overview of esophageal disorders from a pathophysiological point of view.

The esophagus serves the principal purpose of transporting food from the pharynx into the stomach. A complex interplay between nerves and muscle fibers ensures that swallowing takes place as a finely coordinated event. Esophageal function can be tested by a variety of methods, endoscopy, manometry, and reflux monitoring being some of the most important. Regarding pathophysiology, motor disorders, such as achalasia, often cause dysphagia and/or chest pain. Functional esophageal disorders are a heterogeneous group with hypersensitivity as a dominant pathophysiological factor. Gastroesophageal reflux disease often causes symptoms, such as heartburn and regurgitation, and a spectrum of disease, ranging from minimal mucosal damage visible only in the microscope to esophageal ulcers and strictures in the most severe cases. Eosinophilic esophagitis is an immune-mediated condition that can result in significant dysphagia and associated luminal narrowing. In the following, we will provide an overview of the most common esophageal disorders from a combined pathophysiological and clinical view.

Recent insights into the biology of Barrett's esophagus.

Barrett's esophagus (BE) is the only known precursor to esophageal adenocarcinoma (EAC), an aggressive cancer with a poor prognosis. Our understanding of the pathogenesis and Barrett's metaplasia is incomplete, and this has limited the development of new therapeutic targets and agents, risk stratification ability, and management strategies. This review outlines current insights into the biology of BE and addresses controversies surrounding cell of origin, cellular reprogramming theories, updates on esophageal epithelial barrier function, and the significance of goblet cell metaplasia and its association with malignant change. Further research into the basic biology of BE is vital as it will underpin novel therapies and improve our ability to predict malignant progression and help identify the minority of patients who will develop EAC.

Mucosal impedance for esophageal disease: evaluating the evidence.

Impedance has traditionally been employed in esophageal disease as a means to assess bolus flow and reflux episodes. Recent and ongoing research has provided new and novel applications for this technology. Measurement of esophageal mucosal impedance, via either multichannel intraluminal impedance catheters or specially designed endoscopically deployed impedance catheters, provides a marker of mucosal integrity. Mucosal impedance has been shown to segregate gastroesophageal reflux disease (GERD) and eosinophilic esophagitis from non-GERD controls and may play a role in predicting response to reflux intervention. More data are needed with regard to other esophageal subgroups, outcome studies, and functional disease. Our paper reviews the history of impedance in esophageal disease, the means of assessing baseline and mucosal impedance, data with regard to the newly developed mucosal impedance probes, the clinical utility of mucosal impedance in specific clinical conditions, and limitations in our existing knowledge, along with suggestions for future studies.

Impedance in the evaluation of the esophagus.

The aim of this paper is to review esophageal electrical impedance technologies and to discuss the use of these technologies for physiological measurements, diagnostics, and therapy of esophageal disease. In order to develop a better understanding of the pathophysiology of and improve the diagnosis of esophageal disorders, such as gastroesophageal reflux disease (GERD) and achalasia, several new diagnostic tests, including intraluminal impedance, esophageal mucosal impedance, and the functional luminal imaging probe, have been developed. These technologies have proven valuable for assessment of the esophagus in recent years. They provide information on esophageal flow properties, mucosal integrity, lumen shape, and distensibility in esophageal disorders, in particular for GERD and achalasia. Despite their promise and novel clinical studies, the potential of these technologies has been far from realized. New multidisciplinary approaches will contribute to our understanding and interpretation of esophageal impedance data and disease mechanisms.

Diagnosis of gastroesophageal reflux: an update on current and emerging modalities.

Gastroesophageal reflux disease (GERD) is a common condition characterized by troublesome symptoms or esophageal mucosal lesions attributed to excessive esophageal acid exposure. Various pathophysiological mechanisms account for GERD, including impaired esophageal peristalsis and anatomical or physiological defects at the esophagogastric junction (EGJ). Endoscopy identifies GERD complications and detects potential alternative diagnoses. However, if symptoms persist despite proton pump inhibitor therapy, functional esophageal tests are useful to characterize reflux burden and define the symptom association profile. Ambulatory pH or pH-impedance monitoring measures the 24-h acid exposure time, which remains the most reproducible reflux metric and predicts response to antireflux therapy. Apart from identifying peristaltic dysfunction, esophageal high-resolution manometry defines the morphology and contractile vigor (EGJ-CI) of the EGJ. Novel metrics obtained from pH-impedance monitoring include the postreflux swallow-induced peristaltic wave index and mean nocturnal baseline impedance, which augment the diagnostic value of pH-impedance testing. Mucosal impedance can also be recorded using a probe inserted through a gastroscope, or a novel balloon catheter with arrays of impedance electrodes inserted following sedated endoscopy. The latest developments in functional esophageal tests define the GERD phenotype based on pathogenesis, reflux exposure, structural or motility disorders, and symptom burden, facilitating appropriate treatment.

Long-term consequences of one anastomosis gastric bypass on esogastric mucosa in a preclinical rat model.

Although bariatric surgery is proven to sustain weight loss in morbidly obese patients, long-term adverse effects have yet to be fully characterized. This study compared the long-term consequences of two common forms of bariatric surgery: one-anastomosis gastric bypass (OAGB) and Roux-en-Y Gastric Bypass (RYGB) in a preclinical rat model. We evaluated the influence of biliopancreatic limb (BPL) length, malabsorption, and bile acid (BA) reflux on esogastric mucosa. After 30 weeks of follow-up, Wistar rats operated on RYGB, OAGB with a short BPL (15 cm, OAGB-15), or a long BPL (35 cm, OAGB-35), and unoperated rats exhibit no cases of esogastric cancer, metaplasia, dysplasia, or Barrett's esophagus. Compared to RYGB, OAGB-35 rats presented higher rate of esophagitis, fundic gastritis and perianastomotic foveolar hyperplasia. OAGB-35 rats also revealed the greatest weight loss and malabsorption. On the contrary, BA concentrations were the highest in the residual gastric pouch of OAGB-15 rats. Yet, no association could be established between the esogastric lesions and malabsorption, weight loss, or gastric bile acid concentrations. In conclusion, RYGB results in a better long-term outcome than OAGB, as chronic signs of biliary reflux or reactional gastritis were reported post-OAGB even after reducing the BPL length in a preclinical rat model.

Development and Validation of a Mucosal Impedance Contour Analysis System to Distinguish Esophageal Disorders.

BACKGROUND & AIMS: Diagnostic testing for chronic esophageal disorders relies on histopathology analysis of biopsies or uncomfortable transnasal catheters or wireless pH monitoring, which capture abnormal intraluminal refluxate. We therefore developed a balloon mucosal impedance (MI) catheter system that instantly detects changes in esophageal mucosal integrity during endoscopy over a long segment of the esophagus. We performed a prospective study to evaluate the ability of a balloon-incorporated MI catheter to detect and evaluate esophageal disorders, including gastroesophageal reflux disease (GERD) and eosinophilic esophagitis (EoE). METHODS: We performed a prospective study of 69 patients undergoing esophagogastroduodenoscopy with or without wireless pH monitoring. Patients were classified as having GERD (erosive esophagitis or abnormal pH; n = 24), EoE (confirmed with pathology analysis of tissues from both distal and proximal esophagus; n = 21), or non-GERD (normal results from esophagogastroduodenoscopy and pH tests; n = 24). Receiver operating characteristic curves and area under the operating characteristic curve (AUC) were used to compare the accuracy of balloon MI in diagnosis. Probabilities of assignment to each group (GERD, non-GERD, or EoE) were estimated using multinomial logistic regression. Association between MI patterns and diagnoses were validated using data from patients seen at 3 separate institutions. RESULTS: MI pattern along the esophageal axis differed significantly (P < .01) among patients with GERD, EoE, and non-GERD. Patients with non-GERD had higher MI values along all measured segments. The MI pattern for GERD was easily distinguished from that of EoE: in patients with GERD, MI values were low in the distal esophagus and normalized along the proximal esophagus, whereas in patients with EoE, measurements were low in all segments of the esophagus. Intercept and rate of rise of MI value (slope) as distance increased from the squamocolumnar junction identified patients with GERD with an AUC = 0.67, patients with EoE with an AUC = 0.84, and patients with non-GERD with an AUC = 0.83 in the development cohort. One patient had an adverse event (reported mild chest pain after the procedure) and was discharged from the hospital without further events. CONCLUSIONS: We developed a balloon MI catheter system that instantly detects changes in esophageal mucosal integrity during endoscopy and found it to be safe and able to identify patients with GERD, EoE, or non-GERD. We validated our findings in a separate cohort for patients. ClinicalTrials.gov ID NCT03103789.

Comparison of mucosal impedance measurements throughout the esophagus and mucosal eosinophil counts in endoscopic biopsy specimens in eosinophilic esophagitis.

BACKGROUND AND AIMS: Assessing eosinophilic esophagitis (EoE) activity from limited esophageal mucosal biopsy samples has been questioned. Here our aim was to compare mucosal impedance (MI) throughout the esophagus and eosinophil counts in endoscopic biopsy samples in EoE. METHODS: We compared 20-site MI using a balloon catheter in the esophagus and eosinophils per high-power field (eos/HPF) in esophageal mucosal biopsy samples. Data are summarized as median (interquartile range) comparing control subjects and EoE using Mann-Whitney rank sum test and between endoscopic reference score and MI (minimal and average) using rank Spearman correlation. RESULTS: Ten adult control patients (ages 38-70) and 23 EoE patients (ages 21-80, 18 active) were studied. The mean (range) pan-esophageal MI in control subjects was significantly higher (6435 ohms [4546-7301]) compared with EoE patients (2004 ohms [1437-2546], P < .001). In control patients 172 of 180 (95.6%) individual impedance measurements (18 per patient) were normal when compared with 126 of 432 (29.2%) measurements in EoE. No EoE patient had uniformly normal MI. MI varied widely, with 19 of 23 patients having values above and below 2300 ohms (normal) regardless of EoE activity. Correlation of maximim eos/HPF with minimum and average MI per patient was r = -.243, P = .072 and r = -.358, P = .086, respectively. Of 5 patients with inactive EoE, 3 had >50% abnormal MI segments. Correlation coefficients of the endoscopic reference score with minimum and average MI were r = -.154, P = .47 and r = -.27, P = .20, respectively. The procedure was <5 minutes without adverse events. CONCLUSIONS: MI is lower in the esophagus of EoE patients compared with control subjects with poor correlation between peak esophageal eosinophil counts, EoE activity, and MI. Segmental esophageal MI provides a unique marker of esophageal dysfunction in EoE. (Clinical trial registration number: NCT02995395.).

Revisiting Montreal: New Insights into Symptoms and Their Causes, and Implications for the Future of GERD.

The Montreal definition of gastroesophageal reflux disease (GERD) provided a rationale for acid suppression medication without investigation, thus enhancing the management of the substantial symptom burden in these patients. Increased proton-pump inhibitor use has also highlighted their limitations, with one third of "typical" symptoms known to be refractory. Most refractory symptoms are ascribed to reflux hypersensitivity (RH) and functional heartburn (FH). RH may be caused by impaired esophageal mucosal barrier function and sensitization of peripheral esophageal receptors. Central sensitization may also contribute to the perception of non-pathologic reflux in RH, and the perception of physiological stimuli in FH. Importantly, mechanisms underlying GERD, RH, and FH are (in theory) not mutually exclusive, further complicating patient management. Methods used to distinguish GERD from RH and FH are impractical for use in epidemiological studies and pragmatic care and may have limited diagnostic accuracy. This is impeding accurate prevalence estimates and risk factor determination and the identification of new therapies. Direct assessment of mucosal barrier function by measuring impedance is a promising candidate for improved diagnosis. Ultimately though the concept of GERD as a composite, symptom-based entity needs re-evaluation, so that new understandings of upper GI symptoms can direct more precise management.

Impairment of rat oesophageal muscle contractility associated with experimental non-erosive oesophageal mucosal damage.

NEW FINDINGS: What is the central question of this study? Is the responsiveness of isolated segments of the rat oesophagus to contractile or relaxant stimuli susceptible to acute luminal exposure of the oesophagus to an acid solution that contains pepsin and bile salt? What is the main finding and its importance? The study reveals that luminal acidity is an important factor that disrupts barrier function in the oesophagus to allow the diffusion of noxious agents, such as bile acid, that alter the contractile status of the oesophageal body, even in the absence of inflammation. ABSTRACT: We investigated whether the experimental simulation of duodenogastro-oesophageal reflux alters the contractile responsiveness of rat oesophageal strips. After 30 min of luminal exposure to a solution at acid pH that contained pepsin and taurodeoxycholic acid, isolated strips of the rat oesophagus and gastro-oesophageal junction were subjected to contractile or relaxing stimuli. Acid challenge decreased the responsiveness of oesophageal strips to contractile stimulation, especially in oesophageal preparations that were mounted following the circular orientation of the muscularis externa layer. The contractility of longitudinal preparations of the rat oesophagus appeared less susceptible to the deleterious effects of acid challenge. In contrast, the responsiveness of ring-like preparations from the gastro-oesophageal junction to contractile stimulation was unaltered by acid challenge. Taurodeoxycholic acid decreased the responsiveness of circular oesophageal preparations to KCl, an effect that was exacerbated by luminal acidity. On the contrary, although the relaxant ability of the rat oesophagus did not change, acid challenge increased the relaxant efficacy of sodium nitroprusside and isoprenaline in strips of the gastro-oesophageal junction. A significant decrease in transepithelial electrical resistance was seen when the oesophageal mucosa was challenged at pH 1 but not at pH 4. Treatment with alginate blunted the deleterious effects of acid challenge on transepithelial electrical resistance and the responsiveness of oesophageal preparations to KCl. The present findings support the notion that luminal acidity is an important factor that disrupts barrier function in the oesophagus to allow the diffusion of noxious agents, such as bile acid, that alter the contractile status of the oesophagus.

Can Eosinophilic Esophagitis Cause Achalasia and Other Esophageal Motility Disorders?

Eosinophilic esophagitis (EoE), a disorder identified by its esophageal mucosal features, often is associated with esophageal motility abnormalities, which are manifestations of esophageal muscle dysfunction. Those motility abnormalities sometimes normalize with treatments that reduce esophageal eosinophilia, suggesting that eosinophils can cause reversible esophageal motility disturbances, perhaps by releasing myoactive and neuroactive eosinophil products. Although achalasia uncommonly is associated with EoE as currently defined, most achalasia patients have evidence of an abnormal accumulation of eosinophils and/or their degranulation products in the esophageal muscularis propria, a location inaccessible to routine endoscopic evaluation. Achalasia is an idiopathic condition resulting from destruction of neurons in the myenteric plexus of the esophagus, and degranulating eosinophils release toxic proteins capable of destroying those neurons, thereby causing the irreversible motility abnormalities of achalasia. This report reviews data on the association of esophageal eosinophilia with achalasia and other esophageal motility abnormalities. Based on this review, we propose that EoE, like eosinophilic gastroenteritis, might have mucosal-predominant and muscle-predominant forms with different clinical manifestations. A muscle-predominant form of EoE could underlie a variety of reversible and irreversible esophageal motility disorders, including achalasia. The concept that esophageal motility abnormalities might develop from a muscle-predominant form of EoE warrants serious consideration and further investigation.

Obesity and GERD impair esophageal epithelial permeability through 2 distinct mechanisms.

BACKGROUND: The 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. METHODS: Twenty-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. RESULTS: One 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. CONCLUSION: Obesity 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.

Mucosal Impedance Measurements Differentiate Pediatric Patients With Active Versus Inactive Eosinophilic Esophagitis.

BACKGROUND AND AIMS: Eosinophilic esophagitis (EoE) is a chronic disorder in children that requires continued assessment of disease activity, involving repeated sedation, endoscopy, and biopsy analysis. We investigated whether mucosal impedance measurements can be used to monitor disease activity in pediatric patients with EoE. METHODS: We measured mucosal impedance at 3 locations in the esophagus in pediatric patients (1-18 years old; 32 with active EoE, 10 with inactive EoE, 32 with nonerosive reflux disease [NERD]) and 53 children with symptoms but normal findings from histologic analyses (controls) undergoing routine esophagogastroduodenoscopy at the Vanderbilt Pediatric Gastroenterology Clinic. Pathologists reviewed biopsies per routine protocol, determined eosinophilic density, and graded spongiosis on an ordinal visual scale. Mucosal impedance measurements were compared within patient groups. The primary outcome was correlation of mucosal impedance measurements with disease activity, based on severity of spongiosis and eosinophil counts. RESULTS: Mucosal impedance measurements were significantly lower in patients with active EoE at 2, 5, and 10 cm above the squamo-columnar junction (median values of 1069, 1368, and 1707, respectively) compared to patients with inactive EoE (median values of 3663, 3657, and 4494, respectively), NERD (median values of 2754, 3243, and 4387), and controls (median values of 3091, 3760, and 4509) (P < 0.001 for all comparisons to patients with active EoE). We found inverse correlations between mucosal impedance measurements and eosinophil count (P < 0.001), and spongiosis severity (P < 0.001). CONCLUSIONS: Mucosal impedance measurements may provide immediate information about mucosal inflammation in children. Patients with active EoE have significantly lower mucosal impedance values than patients with inactive EoE, NERD, or controls; mucosal impedance measurements correlate inversely with eosinophil counts and spongiosis severity. Mucosal impedance is a promising rapid and less-invasive method to monitor EoE activity in pediatric patients with EoE; it could reduce costs and risks of disease monitoring.

Pathophysiology of Gastroesophageal Reflux Disease.

The pathogenesis of gastroesophageal reflux disease (GERD) is complex and involves changes in reflux exposure, epithelial resistance, and visceral sensitivity. The gastric refluxate is a noxious material that injures the esophagus and elicits symptoms. Esophageal exposure to gastric refluxate is the primary determinant of disease severity. This exposure arises via compromise of the anti-reflux barrier and reduced ability of the esophagus to clear and buffer the refluxate, leading to reflux disease. However, complications and symptoms also occur in the context of normal reflux burden, when there is either poor epithelial resistance or increased visceral sensitivity. Reflux therefore develops via alterations in the balance of aggressive and defensive forces.

Herniación de la mucosa esofágica tras diverticulectomía epifrénica / Herniation of the esophageal mucosa after epiphrenic diverticulectomy

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