Comparison of clinical and pharmacodynamic features of proton pump inhibitors efficacy in gastroesophageal reflux disease

The aim of review. To present literature data on clinical presentation, pharmacodynamic and economic efficiency of standard dozes of proton pump inhibitors (PPI) for gastroesophageal reflux disease (GERD).Summary. PPI are the most effective pharmaceuticals for treatment of acid-related diseases (ARD). Control of intragastric рН level is the key moment of healing of erosions and ulcers of the upper gastro-intestinal tract, as well as for Н. рylori eradication efficacy. Functional state of stomach mucosa and efficacy of antisecretory therapy was estimated by 24-hour pH or рН-impedance measurement. The standard dozes of PPI provided acid-suppressive effect for up to 18 hs. Already after the first dose intake at 24-hour рН monitoring the stomach рН>3 was recorded for 56,1% (±20,94) of total monitoring time, and рН>4 — for 44,0% (±18,72), that promoted rapid symptom relief. Terms of activation and efficacy of Н+/К+-ATPase inhibitors is determined by pH of the media and pKa values for each pharmaceutical. Intensity of acid-suppressive action of PPI depends on drug metabolic pathways and genetically determined features of cytochrome P450 system. Mutations of CYP2C19 alleles allow to divide the studied patients population into groups of rapid, mediun and slow «metabolizers» that it is necessary to take into account at prescription of the certain drug. At a choice of PPI dose or shift from one PPI to another it is necessary to be guided by the concept of equivalent dosages according to the instruction leaflet on the drug application. Long-term maintenance therapy by PPI for GERD enables reduction of expenses for treatment of disease preserving clinical efficacy.Conclusion. PPI are of the drugs of choice in ARD therapy. PPI should be applied in the least effective doze, including on demand treatment and intermittent treatment. The individual approach to PPI prescription, based on the careful analysis of clinical presentation, as well as on data of esophagogastroduodenoscopy, 24-hour pH or pH plus impedance measurement is required. Reasonable cost to efficacy ratio is no less important

European Society for Neurogastroenterology and Motility Consensus on Gastroparesis: What Issues Remain Unresolved?

Aim: to analyse the document of the European Society for Neurogastroenterology and Motility consensus on gastroparesis, held in 2020.Key findings. The evaluation of the voting results on the submitted statements of the consensus meeting shows that there is a high level of agreement among the experts regarding the definition of gastroparesis, the main diseases in which it occurs, and the existing diagnostic methods. At the same time, there is a divergence of views regarding the role of individual pathogenetic factors of gastroparesis and their relationship with clinical symptoms, as well as the effectiveness of drugs of various groups and other treatment methods.Conclusion. The pathophysiological mechanisms of gastroparesis and the effectiveness of various treatment methods need further research

Options of improvement of efficacy of gastroesophageal reflux disease treatment by dioctaedric smectite

Aim of investigation. To analyze efficacy of heartburn relief and pathological gastroesophageal reflux (GER) elimination as well as dynamics of endoscopic changes at gastroesophageal reflux disease (GERD) under dioctaedric smectite (Smecta) treatment in standard doze as monotherapy and within complex mode of treatment.Material and methods. Overall 45 case records of GERD patients (25 women and 20 men, mean age 43,06 years) were analyzed. All patients underwent esophagogastroduodenoscopy (EGDS) and 24-hour рН-impedance recording prior to the treatment onset and at the 14-th day of therapy. The first group included patients with erosive esophagitis (EE) of the I–II degree receiving combination of proton pump inhibitors (PPI) and Smecta, the second group included patients with EE, receiving PPI monotherapy, the third group — patients with non-erosive reflux disease (NERD) at Smecta monotherapy.Results. On a background of treatment by PPI + Smecta relief of heartburn was achieved at the 3rd day in 10 (66,7%) patients, at PPI monotherapy — in 4 (26,7%) patients with EE, at monotherapy by Smecta — in 6 (40%) patients. At the 5th day heartburn has been completely relieved in 11 (73,3%), 9 (60%) and 8 (53,3%), and at the 14-th day — in 13 (86,7%), 11 (73,3%) and 12 (80%) patients respectively. In the first group according to upper endoscopy data healing of erosions was confirmed in 13 (86,7%) patients, in the second — in 10 (66,7%). In the third group cessation of catarrhal signs was revealed in 13 (86,7%) patients. According to 24-hour рН-impedance esophageal recording prior at the beginning of therapy pathological acidic, weakly acidic and weakly alkalinic GERs were diagnosed in 34 (75,5%), 18 (40%) and 12 (26,7%) patients in group as a whole respectively. On a background of therapy by PPI + Smecta acidic refluxes have been eliminated in 14 (93%), at PPI monotherapy — in 11 (73%), at Smecta monotherapy — in 100% of patients. In the first group weakly acidic refluxes disappeared in 2 (67%), in the second — in 1 (50%), in the third – in 9 (69%) cases, weakly alkaline refluxes: in 4 (80%), in 2 (40%) and in 100% of cases respectively.Conclusions. Addition of Smecta in treatment mode at erosive form of GERD essentially increases treatment response rate, significantly reducing terms of clinical improvement onset. Dioctaedric smectite appears an effective drug as monotherapy of NERD. The chief advantage in treatment of GERD is ability of the drug to stop all reflux types: acidic, weakly acidic, and weakly alkalinic

Cardiac achalasia: modern concepts on etiology, pathogenesis, clinical presentation and diagnostics

The aim of review. To present up-to-date data on etiology, pathogenesis, clinical presentation and diagnostics of cardiac achalasia.Key points. Cardiac achalasia represents primary esophageal motor disease with involvement of myenteric plexus. Basic symptoms of achalasia include dysphagia, regurgitation, chest pain and weight loss. Esophageal manometry which allows to evaluate resting pressure and relaxation phenomenon of the lower esophageal sphincter and peristaltic activity of distal part of the esophagus is the «gold standard» of diagnostics. Genetic, autoimmune and infectious theories are considered for disease etiology.Conclusion. For the present moment pathogenesis, clinical presentation and diagnostics methods of cardiac achalasia are investigated in detail, however etiology of disease remains unknown, despite of centuries-old history. The major attention is drawn to autoimmune theory which requires further investigations

Efficacy of Topical Corticosteroid Monotherapy in Inducing and Maintaining Clinical and Histologic Remission in Adolescent and Adult Patients with Eosinophilic Esophagitis: a Systematic Review and Meta-Analysis

Background: Eosinophilic esophagitis (EoE) is the second most common cause of esophagitis. Topical steroids represent a promising group of drugs for inducing and maintaining clinical and histological remission in these patients.Objective. To evaluate the effectiveness of topical steroids in inducing and maintaining clinical and histological remission in adolescent and adult patients with EoE.Methods. A systematic literature search using defined keywords was performed up to March 20, 2021 in the MEDLINE / PubMed, EMBASE (Excerpta Medica), and Cochrane Central Register of Controlled Trials, ClinicalTrial.gov databases.Results. 390 patients from 5 studies were included in this systematic review with meta-analysis. The meta-analysis showed that topical steroids, compared with placebo, was more effective in inducing (odds ratio (OR) 75.77; 95 % confidence interval (CI): (21.8; 263.41), p < 0.001) and maintaining complete histological remission (OR 103.65; 95 % CI: (36.05; 298.01), p < 0.001) in patients with EoE. Also, topical steroids significantly relieved disease symptoms compared with placebo in inducing and maintaining clinical remission (OR 4.86; 95 % CI: (1.4; 16.86), p = 0.01) and (OR 11.06; 95 % CI: (4.62; 26.45), p < 0.001) respectively.Conclusions. Topical steroids represent an effective group of drugs for inducing and maintaining histologic and clinical remission in adolescent and adult patients with EoE

Results of long-term follow-up of patients with chronic gastritis after <i>H. pylori</i> eradication

The aim of publication. To analyze approach for long-term management of patients with chronic gastritis after H. pylori eradication for stomach cancer prevention by the example of clinical cases.Key points. The management approach of patients with chronic gastritis after eradication of H. pylori is presented by the example of patients with various risk of development of stomach cancer. In one and half year after successful eradication therapy in 57 year-old female patient mild atrophy and intestinal metaplasia of antrum without atrophy and intestinal metaplasia of corpus of the stomach was confirmed. At absence of other risk factors for cancer development further endoscopic follow-up is not required. Monitoring of 62 year-old male patient after successful eradication for 5 years has shown stable morphological pattern without progression of premalignant lesions. Taking into account both severe atrophy and intestinal metaplasia of antral region and mild atrophy of body of the stomach, as well as positive family history, esophagogastroscopy with biopsy is recommended once per year to this patient.Conclusion. Prognosis and management approach of patients after eradication of H. pylori infection are determined by chronic gastritis in relation to severity of atrophy and intestinal metaplasia of antral region and corpus of the stomach, along with other risk factors for cancer development e.g. positive family history

High resolution manometry and new classification of esophageal motility disorders

Purpose of the review. To present application of Chicago classification criteria of esophageal motility disorders defined in high resolution manometry in clinical practice. Basic provisions. High-resolution manometry is the most exact hi-tech diagnostic method for esophageal motor function disorders according to Chicago classification v3.0. Uniqueness of the method consists in capacity to define integrated quantitative and qualitative metrics of esophageal contractile function and to establish their specific disorders e.g.: change of intrabolus pressure at disorders of esophagogastric junction (EGj) outflow, hypercontractile esophagus, fragmented contractions and weak or failed peristalsis, distal esophageal spasm. Assessment of the type of achalasia subtypes has significant impact on the patients’ treatment choice. According to anatomical location of the lower esophageal sphincter and crural diaphragm several morphological types of gastro-esophageal junction are defined that determine severity of gastroesophageal reflux disease. Multiple rapid swallow responses during esophageal high-resolution manometry reflect esophageal body peristaltic reserve and is a predictor of postoperative complications. Differential diagnosis of belching type became possible at combined application of high-resolution manometry and impedance measurement. Conclusion. High-resolution manometry is a fundamental diagnostic test of esophageal motor function disorders. Clinical application of this method significantly expands diagnostic potential and allows to carry out personalized treatment that increases treatment quality

Dysplasia of stomach epithelium at chronic <i>H. pylori</i>-associated gastritis: is everything quite so simple?

The aim of publication. Analysis of clinical cases demonstrating differentiated management approach at chronic H. pylori-associated gastritis with stomach epithelium dysplasia.Key points. Detection of high grade (severe) dysplasia is associated to high risk of early, invasive stomach cancer or its rapid development. In presented clinical case adenocarcinoma has been found in 60 year-old male patient with deep submucosa invasion simultaneously with high grade dysplasia. According to comprehensive endoscopic investigation endoscopic treatment option was considered impossible and patient underwent distal subtotal stomach resection with Roux-en-Y anastomosis and D2 regional lymph node dissection. At low grade (mild) dysplasia complex endoscopic investigation is recommended to identify local premalignant lesions of the stomach mucosa, and at ruling them out — to determine adequate therapy. So, in presented clinical case H. pylori eradication therapy in 45-year old patient has led to disappearance of changes suspicious to epithelial dysplasia. The term «indefinite for dysplasia» is applied to atypical changes which can be characterized as of premalignant or reactive nature. It is provisional conclusion which requires specifying endoscopy with guided biopsy and repeated histological conclusion.Conclusion. Prognosis and management approach in the cases with histological conclusion of stomach epithelium dysplasia should be determined according to comprehensive multimodal endoscopic investigation with guided biopsy

Macrophage phenotype after human refluxate exposure, esophageal dysmotility and their correlation with gastroesophageal reflux disease

Aim of the study. To investigate the esophageal dysmotility, changes in the esophageal mucosa and the immune response depending on the type of refluxate in gastroesophageal reflux disease (GERD) patients.Material and methods. 68 patients with GERD were recruited: 28 (14 men; mean age, 45.74 ± 2.23 years) nonerosive reflux disease (NERD), 22 (15 men; mean age, 45.0 ± 3.24 years) erosive reflux disease (EE), 18 (13 men; mean age, 47.22 ± 2.95) Barrett’s Esophagus (BE). GERD patients underwent esophageal high-resolution manometry (HRM) with a 22-channel water-perfused catheter and Solar GI system (Medical Measurements Systems, Enschede, the Netherlands), 24-hour impedance and pH monitoring using the Ohmega Ambulatory Impedance pH Recorder (Medical Measurements Systems). We analyzed receptor characteristics of monocyte-derived macrophages in all groups of patients.Results. On HRM examination, we showed that DCI (distal contractile integral) in NERD patients was higher than in EE (p = 0.088) and BE (p = 0.076), also LES RP (lower esophageal sphincter resting pressure) in NERD patients was higher than in EE (p = 0.039) and BE (p = 0.012). The analysis of reflux characteristics showed that the total reflux time with pH &lt; 4 for BE patients was longer than that for NERD and EE patients. An analysis of receptor characteristics of monocyte-derived macrophages showed the prevalence of CD25 and CD80 expression in all groups of patients.Conclusion. An analysis of the phenotype of macrophages derived from blood monocytes of GERD patients revealed a prevalence of М1 macrophages that was typical for the Th1 type of immune response. The degree of esophageal dysmotility was correlated with GERD severity and type