Mucosal integrity and sensitivity to acid in the proximal esophagus in patients with gastroesophageal reflux disease

Acid reflux episodes that extend to the proximal esophagus are more likely to be perceived. This suggests that the proximal esophagus is more sensitive to acid than the distal esophagus, which could be caused by impaired mucosal integrity in the proximal esophagus. Our aim was to explore sensitivity to acid and mucosal integrity in different segments of the esophagus. We used a prospective observational study, including 12 patients with gastroesophageal reflux disease (GERD). After stopping acid secretion-inhibiting medication, two procedures were performed: an acid perfusion test and an upper endoscopy with electrical tissue impedance spectroscopy and esophageal biopsies. Proximal and distal sensitivity to acid and tissue impedance were measured in vivo, and mucosal permeability and epithelial intercellular spaces at different esophageal levels were measured in vitro. Mean lag time to heartburn perception was much shorter after proximal acid perfusion (0.8 min) than after distal acid perfusion (3.9 min) ( P = 0.02). Median in vivo tissue impedance was significantly lower in the distal esophagus (4,563 Ω·m) compared with the proximal esophagus (8,170 Ω·m) ( P = 0.002). Transepithelial permeability, as measured by the median fluorescein flux was significantly higher in the distal (2,051 nmol·cm−2·h−1) than in the proximal segment (368 nmol·cm−2·h−1) ( P = 0.033). Intercellular space ratio and maximum heartburn intensity were not significantly different between the proximal and distal esophagus. In GERD patients off acid secretion-inhibiting medication, acid exposure in the proximal segment of the esophagus provokes symptoms earlier than acid exposure in the distal esophagus, whereas mucosal integrity is impaired more in the distal esophagus. These findings indicate that the enhanced sensitivity to proximal reflux episodes is not explained by increased mucosal permeability.

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Tu1240 Mucosal Integrity and Sensitivity to Acid of the Proximal Esophagus in Patients With Gastroesophageal Reflux Disease

Gastrointestinal Endoscopy ◽

10.1016/j.gie.2016.03.1219 ◽

2016 ◽

Vol 83 (5) ◽

pp. AB588-AB589

Author(s):

Froukje B. van Hoeij ◽

Pim Weijenborg ◽

Marius van den Bergh Weerman ◽

René M. van den Wijngaard ◽

Wouter De Jonge ◽

...

Keyword(s):

Gastroesophageal Reflux Disease ◽

Gastroesophageal Reflux ◽

Reflux Disease ◽

Mucosal Integrity ◽

Proximal Esophagus

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Gastroesophageal reflux disease: new approaches to optimizing pharmacotherapy

Medical Council ◽

10.21518/2079-701x-2021-5-30-37 ◽

2021 ◽

pp. 30-37

Author(s):

D. N. Andreev ◽

A. V. Zaborovsky ◽

E. G. Lobanova

Keyword(s):

Gastroesophageal Reflux Disease ◽

Gastroesophageal Reflux ◽

Reflux Disease ◽

Barrier Properties ◽

Nerve Fibers ◽

Esophageal Mucosa ◽

Mucosal Permeability ◽

Other Substances ◽

Maintenance Of Remission

Proton pump inhibitors (PPIs) are baseline drugs for induction and maintenance of remission in gastroesophageal reflux disease (GERD). PPIs have proven to be highly effective in healing esophageal mucosal lesions and relieving the symptoms of the disease in most cases. However, according to the literature data, the incidence rate of clinical ineffectiveness of PPIs in the form of partial or complete persistence of current symptoms during administration of standard doses of PPIs ranges from 10 to 40%. Optimization of GERD therapy in PPI refractory patients is a significant challenge. In most cases, experts advise to increase a dose / dosage frequency of PPIs, switch to CYP2C19-independent PPIs (rabeprazole, esomeprazole, dexlansoprazole), add an esophagoprotective or promotility agents to therapy. At the same time, these recommendations have a limited effect in some patients, which opens up opportunities for looking for new solutions related to the optimization of GERD therapy. Today there is growing evidence of the relevance of the role of disruption of the cytoprotective and barrier properties of the esophageal mucosa in the genesis of GERD and the formation of refractoriness. Intercellular contacts ensure the integrity of the barrier function of the esophageal mucosa to protect it from various exogenous intraluminal substances with detergent properties. Acid-peptic attack in patients with GERD leads to alteration of the expression of some tight junction proteins in epithelial cells of the esophageal mucosa. The latter leads to increased mucosal permeability, which facilitates the penetration of hydrogen ions and other substances into the submucosal layer, where they stimulate the terminals of nerve fibers playing a role in the induction and persistence of the symptoms of the disease. The above evidence brought up to date the effectiveness study of the cytoprotective drugs with tropism to the gastrointestinal tract, as part of the combination therapy of GERD.

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DIAGNOSTIC VALUE OF MORPHOLOGICAL CHANGES IN GASTROESOPHAGEAL REFLUX DISEASE IN BIOPSY MATERIAL OF THE DISTAL ESOPHAGUS IN ADOLESCENTS SICKLY WITH ACUTE RESPIRATORY DISEASES

EUREKA Health Sciences ◽

10.21303/2504-5679.2019.00847 ◽

2019 ◽

Vol 1 ◽

pp. 15-23

Author(s):

Olena Zhuravel ◽

Tetyana Pochinok ◽

Tamara Zadorozhna ◽

Tetyana Archakova ◽

Valentyna Zamula

Keyword(s):

Gastroesophageal Reflux Disease ◽

Gastroesophageal Reflux ◽

Mucous Membrane ◽

Reflux Disease ◽

Respiratory Diseases ◽

Morphological Changes ◽

Diagnostic Value ◽

Distal Esophagus ◽

Biopsy Material ◽

Acute Respiratory Diseases

The article dedicated to the problem of the diagnostic value of morphological changes in gastroesophageal reflux disease in the biopsy of the distal esophagus in pubertal children of childbearing age. Aim of the research is to investigate the diagnostic value of morphological changes in gastroesophageal reflux disease in esophageal biopsy material in adolescents sickly with acute respiratory diseases. Methodology. The objective of the study was achieved through examination of 90 adolescents (10 to 16 years old, average age 13.1±3.54 years) kept under observation at the Children’s Clinical Hospital No. 9 of Kyiv and on the basis of the Department of Pediatrics No. 1 Center of Primary Health Care No. 4 of the Desnianskyi district of Kyiv. All adolescents belonged to the group of sickly with a number of respiratory diseases averaging 6-8 times a year, lasting from 8 to 18 days (on average 12.8±5.41 days). All children have undergone endoscopic examination of the esophagus, stomach and duodenum with the esophagus mucosa biopsy using the OLYMPUS GIF-P3 flexible fiberscope. Results. It was found that the least valuable diagnostic feature in the morphological examination of the mucous membrane of the distal esophagus in the pain-causing children with GERD was thickening of the epithelium with a sensitivity of 13,0 %, a specificity of 96.0 %, and total value of 65.0 %. It has been proved that hyperplasia of cells of the basal layer of the mucous membrane of the distal esophagus at the GERD in the infected children is 46.7 % (specificity – 93.3 %, the total value is 75.6 %). Increase in the number of papillae and their prolongation in 33.3 % cases (sensitivity – 33.3 %, specificity – 93.3 %, overall diagnostic value – 70.8 %). Conclusion. The peculiarity of the morphological manifestations of GERD in childbearing children is dystrophic changes in keratocytes in the superficial parts of the multilayer squamous epithelium, which are detected at 100.0 % of patients (specificity is 93.3 %, total value is 96.8 %), with parakeratosis centers at 13.3 % of cases. It has been shown that a frequent and diagnostically valuable indication is inflammatory infiltration of the esophageal mucosa, which are verified in all cases (100.0 %, with dilatation and hyperemia in 46.7 % of patients (specificity – 40.0 %, total value – 81.3 %).

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Asymmetrical Gastroesophageal Acid Reflux in Distal Esophagus of Patients With Gastroesophageal Reflux Disease – Examinations With Newly Developed pH Sensor Catheter Equipped With 8 pH Sensors

Gastroenterology ◽

10.1016/s0016-5085(11)62568-7 ◽

2011 ◽

Vol 140 (5) ◽

pp. S-620

Author(s):

Shunji Ohara ◽

Kenji Furuta ◽

Shino Shimura ◽

Kousuke Fukazawa ◽

Masahito Aimi ◽

...

Keyword(s):

Gastroesophageal Reflux Disease ◽

Gastroesophageal Reflux ◽

Reflux Disease ◽

Ph Sensor ◽

Acid Reflux ◽

Distal Esophagus ◽

Ph Sensors

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Esophageal mucosal integrity improves after laparoscopic antireflux surgery in children with gastroesophageal reflux disease

Surgical Endoscopy ◽

10.1007/s00464-016-5304-0 ◽

2016 ◽

Vol 31 (7) ◽

pp. 2910-2917 ◽

Cited By ~ 4

Author(s):

Femke A. Mauritz ◽

Nicolaas F. Rinsma ◽

Ernest L. W. van Heurn ◽

Cornelius E. J. Sloots ◽

Peter D. Siersema ◽

...

Keyword(s):

Gastroesophageal Reflux Disease ◽

Gastroesophageal Reflux ◽

Reflux Disease ◽

Antireflux Surgery ◽

Laparoscopic Antireflux Surgery ◽

Mucosal Integrity

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Sa1311 Real-Time Endoscopy-Guided Measurement of Mucosal Admittance to Diagnose Mucosal Integrity in Patients With Gastroesophageal Reflux Disease

Gastroenterology ◽

10.1016/s0016-5085(16)30982-9 ◽

2016 ◽

Vol 150 (4) ◽

pp. S278

Author(s):

Tomoaki Matsumura ◽

Makoto Arai ◽

Mai Fujie ◽

Hideaki Ishigami ◽

Kenichiro Okimoto ◽

...

Keyword(s):

Gastroesophageal Reflux Disease ◽

Gastroesophageal Reflux ◽

Real Time ◽

Reflux Disease ◽

Mucosal Integrity

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The relationship of gastroesophageal reflux disease with adenocarcinoma of the distal esophagus and cardia

Gastroenterology ◽

10.1016/s0016-5085(00)82051-x ◽

2000 ◽

Vol 118 (4) ◽

pp. A1535

Author(s):

Vic Velanovich ◽

John Hollingsworth ◽

Preetham Suresh

Keyword(s):

Gastroesophageal Reflux Disease ◽

Gastroesophageal Reflux ◽

Reflux Disease ◽

Distal Esophagus ◽

Relationship Of ◽

The Relationship

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Effect of proton pump inhibitors on cytochrome P450 2c19 activity in patients with gastroesophageal reflux disease.

Clinical Medicine (Russian Journal) ◽

10.18821/0023-2149-2018-96-2-164-167 ◽

2018 ◽

Vol 96 (2) ◽

pp. 164-167

Author(s):

Yuliya S. Rabotyagova ◽

I. L. Klyaritskaya ◽

Anil Modak

Keyword(s):

Enzyme Activity ◽

Gastroesophageal Reflux Disease ◽

Gastroesophageal Reflux ◽

Proton Pump Inhibitors ◽

Proton Pump ◽

Reflux Disease ◽

Non Invasive ◽

Cytochrome P450 2C19 ◽

Concomitant Medications

Patients with gastroesophageal reflux disease (GERD) are routinely prescribed one of the six proton pump inhibitors (PPI). All of these PPI are inhibitors of CYP2C19 enzyme to varying degrees. The phenotype 13C-pantoprazole breath test (Ptz-BT) was used to identify patients who are poor metabolizers (PM) and the extent of phenoconversion of CYP2C19 enzyme activity caused by four PPI (omeprazole, esomprazole pantoprazole and rabeprazole) in 54 newly diagnosed GERD patients prior to initiating randomly selected PPI therapy and 30 days after PPI therapy. The phenoconversion after 30 days of PPI therapy in GERD patients was statistically significant (p = 0.001) with omeprazole/esomeprazole (n = 27) strong CYP2C19 inhibitors, while there was no change in CYP2C19 enzyme activity (p = 0.8) with pantoprazole/rabeprazole (n = 27), weak CYP2C19 inhibitors. The rapid, in vivo, and non-invasive phenotype Ptz-BT can evaluate CYP2C19 enzyme activity. More importantly, it can identify GERD patients with low CYP2C19 enzyme activity (PM), caused by PPI or other concomitant medications, who would benefit from dose adjustments to maintain efficacy and avoid toxicity. The existing CYP2C19 genotype tests cannot predict the phenotype nor can it detect phenoconversion due to nongenetic factors.

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