Duodenogastroesophageal Reflux Research Articles

Development of a new endoscopy system to visualize bilirubin for the diagnosis of duodenogastroesophageal reflux.

Reflux hypersensitivity (RH) is a form of refractory gastroesophageal reflux disease in which duodenogastroesophageal reflux (DGER) plays a role. This study aimed to determine the usefulness of an endoscopy system equipped with image-enhanced technology for evaluating DGER and RH. The image enhancement mode for detecting bilirubin and calculated values were defined as the Bil mode and Bil value, respectively. First, the visibility of the Bil mode was validated for a bilirubin solution and bile concentrations ranging from 0.01% to 100% (0.002-20 mg/dL). Second, visibility scores of the Bil mode, when applied to the porcine esophagus sprayed with a bilirubin solution, were compared to those of the blue laser imaging (BLI) and white light imaging (WLI) modes. Third, a clinical study was conducted to determine the correlations between esophageal Bil values and the number of nonacid reflux events (NNRE) during multichannel intraluminal impedance-pH monitoring as well as the utility of esophageal Bil values for the differential diagnosis of RH. Bilirubin solution and bile concentrations higher than 1% were visualized in red using the Bil mode. The visibility score was significantly higher with the Bil mode than with the BLI and WLI modes for 1% to 6% bilirubin solutions (P < 0.05). The esophageal Bil value and NNRE were significantly positively correlated (P = 0.031). The area under the receiver operating characteristic curve for the differential diagnosis of RH was 0.817. The Bil mode can detect bilirubin with high accuracy and could be used to evaluate DGER in clinical practice.

Подходы к терапии ГЭРБ с учетом разнообразия ее клинических форм

Approximately one third of gastroesophageal reflux disease (GERD) patients are resistant or partially responsive to proton pump inhibitors (PPIs). It is assumed that non-acid reflux is the cause of 15–62% of cases concerning the PPI therapy inefficacy in GERD patients. The review reveals the issues on the prevention and therapy of non-acid GERD types, ways to improve the treatment efficacy. Understanding the patterns of reflux and pathogenetic mechanisms of non-acid GERD types makes it possible to choose the right drugs. For the prevention and treatment of bile reflux, it is necessary to normalize esophageal, gastric and duodenal motility, as well as biliary system function, and prescribe adequate antisecretory and cytoprotective therapy. The basic drugs for the GERD treatment are PPIs. In order to elevate the GERD therapy effect, drugs are used that can enhance the protective factors of the mucous membranes, i.e., cytoprotectors. UDCA drugs are the basis of GERD therapy with a predominance of bile reflux. Prokinetics are used in the treatment of duodenogastroesophageal reflux to normalize the biliary system function, as well as the motor-evacuation function of the stomach and intestines. Heterogeneity of pathogenesis, including the possibility of acid and non-acid gastroesophageal reflux, necessitates GERD differentiated therapy. KEYWORDS: GERD, reflux, prokinetic, gastroprotectors, cytoprotector, proton pump inhibitors. FOR CITATION: Seliverstov P.V., Lazareva Yu.A., Egorov D.V. Methods for GERD therapy according to its clinical form diversity. Russian Medical Inquiry. 2023;7(7):432–438 (in Russ.). DOI: 10.32364/2587-6821-2023-7-7-5.

Small hiatal hernias: clinical manifestations, sleep disorders and quality of life

Purpose of the study : to identify the features of clinical manifestation, sleep disorders and quality of life in patients with small hiatal hernias in gastroesophageal (GER) and duodenogastroesophageal refl ux (DGER). Materials and methods . 120 patients with small (1–2 degrees) hiatal hernias and grade I–III refl ux esophagitis on the basis of predominantly GER (35 people) and DGER (85 people) refl ux were examined. Sleep disorders were assessed using the Yu. A. Aleksandrovsky scale, violations of the quality of life — the KSC RAMS questionnaire. Results. Small hiatal hernias in all cases occur with a pronounced refl ux syndrome in the form of combination of esophageal and extraesophageal manifestations, developing both on the basis of GER and DGER. Esophageal manifestations of refl ux syndrome predominate in the presence of DHER and are combined with biliary dyspepsia. Extraesophageal manifestations do not depend on the type of refl ux. Dyssomnia was noted in every second patient with hiatal hernia, primarily presomnic and intrasomnic disorders, which were most pronounced in patients with GER. In the majority of patients with small hiatal hernias, the main reasons for the decrease in the quality of life, regardless of the type of refl ux into the esophagus, were the need for treatment, adherence to a diet, instrumental studies, and restriction of physical activity.

Predictive value of dysplastic-dependent phenotypic and visceral manifestations in gastroesophageal refl ux disease associated with duodenogastroesophageal reflux

Purpose of the study : to identify and evaluate the prognostic role of phenotypic and visceral stigmas of connective tissue dysplasia in the formation of gastroesophageal refl ux disease (GERD) associated with duodenogastroesophageal refl ux (DHER). Materials and methods . In an analytical one-stage study 129 (42 men and 87 women) patients with GERD associated with DHER (GERD-DHER), verifi ed by the presence of refl ux esophagitis and the data of esophageal pH-metry, were examined to diagnose the presence / absence of a dysplastic- dependent phenotype and visceral signs of connective tissue dysplasia. Results . In the adult population of GERD-DHER patients, phenotypic and visceral manifestations of connective tissue dysplasia occur in 45,7% of cases. The chance of developing the disease in persons with a dysplastic- dependent phenotype in the presence of a hiatal hernia increases by 3,7 times, with a combination of a hiatal hernia and anomalies in the shape of the gallbladder — 4,3 times; in the presence of cardia insuffi ciency, anomalies in the shape of the gallbladder and their combination — by 1,4–1,6 times.

Functional, Diagnostic and Therapeutic Aspects of Bile.

Bile is a unique body fluid synthesized in our liver. Enterohepatic circulation preserves bile in our body through its efficient synthesis, transport, absorption, and reuptake. Bile is the main excretory route for bile salts, bilirubin, and potentially harmful exogenous lipophilic substances. The primary way of eliminating cholesterol is bile. Although bile has many organic and inorganic contents, bile acid is the most physiologically active component. Bile acids have a multitude of critical physiologic functions in our body. These include emulsification of dietary fat, absorption of fat and fat-soluble vitamins, maintaining glucose, lipid, and energy homeostasis, sustenance of intestinal epithelial integrity and epithelial cell proliferation, reducing inflammation in the intestine, and prevention of enteric infection due to its antimicrobial properties. But bile acids can be harmful in certain altered conditions like cholecystectomy, terminal ileal disease or resection, cholestasis, duodenogastric bile reflux, duodenogastroesophageal bile reflux, and bile acid diarrhea. Bile acids can have malignant potentials as well. There are also important diagnostic and therapeutic roles of bile acid and bile acid modulation.

Quantification and identification of bile acids in saliva by liquid chromatography-mass spectrometry: Possible non-invasive diagnostics of Barrett's esophagus?

Bile acids are a group of steroid compounds essential for lipid digestion. However, when bile acids are refluxed into the stomach and the esophagus, during the so called duodenogastroesophageal reflux, they can have a detrimental effect on the esophageal epithelium and cause pathological changes of esophageal tissue, e.g., Barrett’s esophagus (BE). The levels of bile acids in saliva could therefore serve as possible biomarkers for the diagnostics of BE. In this work, we focused on optimization of sample collection and preparation by solid-phase extraction and subsequent quantification of 11 bile acids (unconjugated, glycine-conjugated) in saliva from healthy volunteers and BE patients by ultra-high-performance liquid chromatography coupled to triple-quadrupole tandem mass spectrometry. Moreover, high resolution MS (Orbitrap-MS) was utilized for identification of new bile acids in saliva. Methods for saliva collection including simple spitting and the Salivette® saliva collection system were compared; the latter was found to be unsuitable due to excessive retention of bile acids in the cotton swab. Methanol with 0.1% formic acid were selected for protein precipitation and bile acid extraction prior to SPE. Separation was performed in gradient elution of methanol and 0.1% formic acid in less than 10 min. Saliva from BE patients contained higher levels of almost all bile acids, and the tested groups could be distinguished by principal component analysis. In untargeted analysis by high resolution MS, taurine-conjugated bile acids and glycine-conjugated dihydroxy-bile acid sulfate were identified in saliva from healthy volunteers. We propose that analysis of salivary bile acids including taurine conjugates could be applicable in diagnostics of BE, following a larger clinical study.

Tactics of managing a patient with fatty liver disease coursing in the background of a polyorgan digestive tract: clinical observation

Preparations of glycyrrhizic acid (GA) and ursodeoxycholic acid (UDCA) are effective in the treatment of various forms of non-alcoholic fatty liver disease (NAFLD) and gastroesophageal reflux disease (GERD) occurring against the background of duodeno-gastroesophageal reflux. However, their effectiveness in the treatment of hologenic diarrhea and reflux gastritis has not been sufficiently studied. Currently, there are no clinical guidelines for the diagnosis and treatment of patients with hologenic diarrhea and reflux gastritis, including those with obesity and NAFLD. It is assumed that the combined administration of GA and UDCA can be accompanied by a mutual potentiation of the effect of the drugs. The article presents a clinical case of a patient with NAFLD, obesity, dyslipidemia, GERD, refractory to treatment with proton pump inhibitors, associated with duodenogastroesophageal reflux, reflux gastritis and hologenic diarrhea. It was shown that GERD, reflux gastritis, and hologenic diarrhea developed in the long-term period after cholecystectomy. At the same time, the appointment of a complex preparation containing GA (35 mg) and UDCA (250 mg) made it possible to stop the manifestations of a typical reflux syndrome in patients with a form of GERD refractory to proton pump inhibitors, reflux gastritis, and diarrheal syndrome associated with an excess of bile acids, improve lipid profile parameters. It has been shown that the administration of GA (35 mg) and UDCA (250 mg) can improve the parameters of the intestinal microbiome and lipid metabolism, which can be used in the treatment of patients with atherogenic dyslipidemia. At the same time, patients with comorbid pathology, including NAFLD, GERD, reflux esophagitis, hologenic diarrhea, and dyslipidemia require long-term maintenance therapy with GA (35 mg) and UDCA (250 mg).

Pathogenetic mechanisms of chronic obstructive pulmonary disease in comorbidity with gastroesophageal reflux disease

The issue of comorbidity of chronic obstructive pulmonary disease with gastroesophageal reflux disease as mutually determined pathological conditions is attracting more and more attention. The aim of the research: to study the pathogenetic mechanisms of the combined course of chronic obstructive pulmonary disease with gastroesophageal reflux disease. Materials and methods: We formed 3 groups of patients: 1 group (n=60) – patients with COPD in combination with GERD, 2 group (n=42) – patients with COPD without signs of GERD, who were treated in the pulmonology department for exacerbation of the disease and group 3 (n=36) – patients with GERD who were treated on an outpatient basis. All patients underwent general clinical examinations and determination of IL-4, IL-6, IFNγ, IFNγ/IL-4, TNF-alpha, pepsinogen and bilirubin levels in saliva Results and Discussion. In patients with concomitant GERD, a significant increase in acute phase indicators in blood serum was found. An increase in the activity of IL-6 and IFNγ cytokines indicates the activation of the cellular link of immunity, with an unregulated immune response that supports chronic inflammation in the bronchi even during remission. The detection of correlations between the concentration of total bilirubin in saliva with a decrease in external respiratory function indicators, namely FJEL, FEV-1, as well as with the presence of shortness of breath allows considering bilirubin as one of the possible markers of reflux and respiratory inflammation in the bronchi, up to the development of obstruction . The positive correlation of pepsinogen-1 in saliva with an allergic history, and pepsinogen-2 with cough, shortness of breath, and smoking, and the negative correlation of pepsinogen-1 with the value of FEV1/FJEL, allows us to consider pepsinogen-1 and pepsinogen-2 as markers of non-acid reflux and respiratory inflammation. Conclusions: Determination of the content of pepsinogens 1 and 2 and bilirubin in saliva are non-invasive methods of detecting duodenogastroesophageal and laryngo-pharyngeal reflux in patients with existing GERD.

Prospects in non-invasive diagnosis of bronchial asthma-related gastroesophageal reflux disease: a single-stage open uncontrolled non-randomised observational study

Background . Respiratory symptoms of bronchial asthma (BA) comorbid with gastroesophageal reflux disease (GERD) may provoke duodenogastroesophageal reflux (DGER) via aggressive agents like pepsinogens and bilirubin. Objectives . A clinical and functional study of the saliva pepsinogen and bilirubin-associated BA-comorbid GERD for non-invasive DGER diagnosis. Methods. A total of 29 patients with an allergic BA phenotype, comorbid GERD and 50 , 2 ± 2 , 4 years mean age have been examined. Biochemical blood panel included bilirubin, C-reactive protein and allergen-specifi c IgE. Saliva bilirubin was estimated in colorimetry, and the pepsinogen-1, -2 content — in immunological tests. Grade A–D reflux oesophagitis (RO) in oesophagoscopy was assigned to erosive reflux disease, and grade N–M oesophageal mucosa (OM) lesions — to non-erosive reflux disease. External respiratory function (ERF) was assessed with forced expiratory volume (FEV 1 , L/s), forced vital capacity (FVC), Tiffeneau index (FEV 1 /FVC), pre- and post-berodual FEF 1 and FVC dynamics. Results. The BA–GERD patients were markedly polymorbid. Cough and chest tightness associated with age, and the tight chest rate — with a higher body mass index and lower FEV 1 /FVC. The association between higher pepsinogen-I and lower FEV 1 /FVC–FVC in response to inhaled berodual, as well as between higher saliva bilirubin and lower FVC–FEV 1 after berodual intake reflects a significant high-DGER effect on BA representation. Conclusion. In BA–GERD patients, saliva pepsinogen and bilirubin are biomarkers of both DGER and respiratory inflammation with bronchospasm.

Pathophysiology of gastroesophageal reflux disease-which factors are important?

Pathophysiology of gastroesophageal reflux disease (GERD) shows a multifactorial background. Different anatomical and functional alterations can be determined such as weakness of the lower esophageal sphincter (LES), changes in anatomy by a hiatal hernia (HH), an impaired esophageal motility (IEM), and/or an associated gastric motility problem with either duodeno-gastro-esophageal reflux (DGER) or delayed gastric emptying (DGE). The purpose of this study is to assess a large GERD-patient population to quantitatively determine different pathophysiologic factors contributing to the disease. For this analysis only patients with documented GERD (pathologic esophageal acid exposure) were selected from a prospectively maintained databank. Investigations: history and physical, body mass index, endoscopy, esophageal manometry, 24 h-pH-monitoring, 24 h-bilirbine-monitoring, radiographic-gastric-emptying or scintigraphy, gastrointestinal quality of life index (GIQLI). In total, 728 patients (420 males; 308 females) were selected for this analysis. Mean age: 49.9 years; mean BMI: 27.2 kg/m2 (range, 20-45 kg/m2); mean GIQLI of 91 (range: 43-138; normal level: 121); no esophagitis: 30.6%; minor esophagitis (Savary-Miller type 1 or Los Angeles Grade A): 22.4%; esophagitis [2-4]/B-D: 36.2%; Barrett's esophagus 10%. Presence of pathophysiologic factors: HH 95.4%; LES-incompetence 88%, DGER 55%, obesity 25.6%, IEM 8.8%, DGE 6.8%. In our evaluation of GERD patients, the most important pathophysiologic components are anatomical alterations (HH), LES-incompetence and DGER.

Systematic review: duodenogastroesophageal (biliary) reflux prevalence, symptoms, oesophageal lesions and treatment.

The prevalence of duodenogastroesophageal reflux (DGER) and its effect on symptoms and oesophageal lesions in gastroesophageal reflux disease (GERD) is unclear. To conduct a systematic review to determine the prevalence of DGER among patients with GERD, the effect of DGER on symptoms and oesophageal lesions, and the treatment of DGER. We searched Pubmed and MEDLINE for full text, English language articles until October 2020 that evaluated DGER prevalence among patients with GERD, the effect of DGER on symptoms and oesophageal lesions, and the treatment of DGER. We identified 3891 reports and included 35 which analysed DGER prevalence in GERD, 15 which evaluated its effect in non-erosive reflux disease (NERD), 17 on erosive oesophagitis, 23 in Barrett's, and 13 which evaluated the treatment of DGER. The prevalence of DGER, when evaluated by Bilitec, among all GERD patients ranged from 10% to 97%, in NERD 10%-63%, in erosive oesophagitis 22%-80% and in Barrett's 50%-100%. There were no differences in the presence or degree of DGER among patients who were asymptomatic or symptomatic on proton pump inhibitors (PPI). The most commonly evaluated treatments for DGER were PPIs and DGER reduced post-PPI therapy in all studies. The prevalence of DGER increased with more advanced oesophageal lesions and did not explain persisting symptoms among patients taking PPI therapy. PPIs appear to be effective in the treatment of DGER. DGER remains an important consideration in patients with GERD and future therapies deserve more study.

Aspiration of conjugated bile acids predicts adverse lung transplant outcomes and correlates with airway lipid and cytokine dysregulation

Duodeno-gastroesophageal reflux aspiration is associated with chronic lung allograft dysfunction (CLAD). Reflux aspirate can contain bile acids (BA), functional molecules in the gastro-intestinal tract with emulsifying properties. We sought to determine and quantify the various BA species in airways of the lung transplant recipients to better understand the various effects of aspirated BA that contribute to post-transplantation outcomes. Bronchial washings (BW) were prospectively collected from lung transplant recipients and subsequently assayed by liquid chromatography-mass spectrometry for 13 BA and 25 lipid families. Patients were monitored for CLAD, rejection, inflammation and airway infections. Detectable BA were present in 45/50 patients (90%) at 3 months after transplant. Elevated BA and predominance of conjugated species were independent predictors of CLAD (hazard ratio 7.9; 95% confidence interval 2.7-23.6; p < 0.001 and 7.3; 2.4-22; p < 0.001, respectively) and mortality (hazard ratio 4.4; 1.5-12.7; p=0.007 and 4.8; 1.4-15.8; p=0.01, respectively). High BA associated with increased positive bacterial cultures (60% vs 25%, p=0.02). Primary conjugated species independently correlated with the rate of bacterial cultures during the first-year post-transplant (Beta coefficient: 0.77; 0.28-1.26; p=0.003) and changes in airway lipidome and cytokines. Higher BA levels and predominance of conjugated BA are independent predictors of chronic lung allograft dysfunction, mortality and bacterial infections. Primary conjugated BA are related to distinct changes in airway lipidome and inflammatory cytokines. This elucidates novel evidence into the mechanism following BA aspiration and proposes novel markers for prediction of adverse post-transplant outcomes.

Bile in excess

The article presents consideration for the pathogenetic mechanisms of the occurrence of duodenogastric reflux (DGR), duodenogastroesophageal reflux (DGER), their role in the occurrence of biliary reflux gastritis and reflux esophagitis. The fundamental bases for the formation of bile reflux are the failure of the sphincter apparatus, antroduodenal dysmotility, elimination of the natural antireflux barrier. Gallbladder dysfunction and duodenal dysmotility are considered the risk factors for primary DGR. The leading mechanism for the development of DGR, DGER after cholecystectomy is a violation of gastroduodenal motility and gastroduodenal hypertension. These syndromes are formed also at gallstone disease and other organic and functional pathological conditions, including pancreatic insufficiency. The syndrome of chronic duodenal hypertension or «duodenal demon» is manifested by heaviness in the epigastrium, belching, heartburn, nausea, vomiting, flatulence, and stool disorders. It is supplemented by the phenomena of psychosomatic asthenization, decreased mental and physical performance, apathy, and a negative assessment of life prospects. The clinical features of hologenous diarrhea are considered, differential diagnostic signs of diarrhea in chronic duodenal hypertension and irritable bowel syndrome are demonstrated.The clinical and pathogenetic substantiation of the treatment of chronic duodenal hypertension accompanied by hologenous diarrhea with colloidal bismuth preparations is presented. The summary of the comparative analysis has been presented of the physicochemical and structural properties of tablet formulations, containing bismuth tripotassium subcitrate, the original drug De‑Nol (Astellas) and the generic Ulcavis (KRKA). It has been concluded that it is advisable to include Ulcavis in the treatment regimen for patients with hologenous diarrhea.

From non-alcoholic fatty liver disease to COVID­19: the present and prospects for the use of ursodeoxycholic acid

The clinical morphological manifestations of the course of non‑alcoholic fatty liver disease in patients, non‑alcohol drinkers, include steatohepatosis, non‑alcoholic steatohepatitis, liver cirrhosis, and hepatocellular carcinoma. There are four basic mechanisms in the pathogenesis of non‑alcoholic fatty liver disease: bile acid lipotoxicity, insulin resistance, systemic inflammation, increased oxidative stress and lipid peroxidation. Non‑alcoholic fatty liver disease increases the risk of onset, development and progression of the cardiovascular diseases independently from other predictors and manifestations of the metabolic syndrome. The complex treatment of patients with coronary heart disease, combined with the non‑alcoholic fatty liver disease includes diet, physical exercises, body mass reduction and drug therapy. The medications for this category of patients must be maximal safe and result in the improving of the clinical, laboratory and morphological parameters of liver. Ursodeoxycholic acid is one of the most effective medications with the mechanisms of action associated with the normalization of the hepatoenteric circulation of bile acids and a number of biologically active substances. It also possesses the cytoprotective and antiapoptotic action, affects the FXR­metabolic nuclear receptor, which plays an important role in the physiology of vascular pathology, is an important transcriptional regulator of bile acids, lipids and glucose metabolism. Ursodeoxycholic acid is able to suppress eosinophilic inflammation not only in the gastrointestinal tract. It improves histopathological changes in airway remodeling, that can be connected with the modulation of cytokines and inhibition of apoptosis of epithelial cells of the respiratory tract. Ursodeoxycholic acid can be potentially effective preparation for the reduction of fluid volume in pulmonary edema and prevention of lung damage caused by fat embolism syndrome. Moreover, its positive effects have been proved as regards the airway epithelial cells at cystic fibrosis. Taking into account that ursodeoxycholic acid inhibits pro‑inflammatory cytokines, has strong antioxidative properties and acts as a famous hepatoprotector, it can be effective in the treatment of coronavirus disease (COVID­19). In Ukraine Ursonost is available, it is one of the well‑known preparations containing ursodeoxycholic acid and advantageously distinguished by high quality and ease of dosing. It is bioequivalent to the reference drug due to the highest quality of the substance and modern production technology. The large evidence base on ursodeoxycholic acid allows the drug Ursonost to be considered as a drug with pronounced multipotent properties, thus it is indicated for the treatment of patients with non‑alcoholic and alcoholic fatty liver disease, especially in combination with the coronary heart disease, of conditions, associated with bile reflux (duodenogastric, duodenogastroesophageal reflux), biliary sludge, primary biliary cirrhosis, gallstone disease (for dissolving X‑ray negative stones) and other metabolic disorders. Ursonost preparation is available as 150 and 300 mg capsules, that facilitates the drug dosing depending on the body mass of a patient and a clinical situation.

Особливості перебігу патології шлунково-кишкового тракту у хворих на гастроезофагеальну рефлюксну хворобу на тлі гіпотиреозу

The article identifies the features of the pathology of the gastrointestinal tract in patients with gastroesophageal reflux disease on the background of hypothyroidism. The frequency of gastroesophageal reflux disease and the severity of this disease increase with age and the presence of comorbid pathology. In the elderly, the frequency of the typical esophageal manifestations decreases, and the erosive esophagitis with atypical symptoms is more common. The growing number of cases of combined thyroid dysfunction with gastropathology requires in-depth study of the reasons for the relationship between these processes. Pathological changes in the gastrointestinal tract in these patients make their condition severer, contributing to the development and progression of metabolic disorders. An important aggravating effect on the regulatory mechanisms of esophageal kinetics has a pathological functioning of the thyroid gland on the background of iodine deficiency. Results and discussion. In patients with gastroesophageal reflux disease with hypothyroidism, all changes in gastric and duodenal function are associated with a decrease in the acid-forming function of the gastric mucosa, due to its atrophy, decreased tone and contractility of the stomach. This in turn leads to a slowing of gastric and duodenal evacuation, dysfunction of the closing capacity of the cardia and, as a consequence, the development of duodenogastroesophageal reflux. The esophageal contents are not so pronounced, so patients with non-erosive forms of esophagitis predominate (46.2%) against 16% of patients in the second group (patients with gastroesophageal reflux disease). At the same time, erosive forms predominate among patients in the control group with predominant acid reflux. It should be noted that there is a clear relationship between the frequency of erosive changes in the esophageal mucosa and the duration of the disease. Thus, among patients of the main group with a 5-year history of the disease, the number of erosive forms of gastroesophageal reflux disease was minimal. The number of erosive changes in the esophageal mucosa increased sharply in patients with a 10-year history and reached its maximum after 15 years from the onset of the disease. Conclusion. The delay in gastric evacuation is more pronounced in patients with gastroesophageal reflux disease on the background of hypothyroidism. It can be explained by a decrease in gastric motility and the presence of duodenostasis. The slowing of gastric evacuation was more pronounced in patients with gastroesophageal reflux disease on the background of reduced thyroid function. In patients with gastroesophageal reflux disease on the background of hypothyroidism there is an alkaline duodenogastroesophageal reflux as a consequence of reduced acid-forming function of the gastric mucosa and reduced contractility of the stomach and duodenum

Duodenogastroesophageal reflux: current state of issue

The article presents data on modern views on the problem of duodenogastroesophageal reflux, examines the key features of the physiology of bile acids, the role of bile acids in the patho- genesis of gastroesophageal reflux disease, Barrett's esophagus and esophageal adenocarcinoma. The review presents current methods for diagnosing duodenogastroesophageal reflux, discusses treatment approaches.

Ассоциация гепатобилиарной патологии и гастроэзофагеальной рефлюксной болезни

The problem of comorbidity with a high risk of polypragmasia is relevant in a large group of patients with diseases in the digestive system. Currently, the problem of comorbidity in patients with gastroesophageal reflux disease (GERD) attracts the attention of specialists due to the high disease prevalence and data indicating its association with other digestive system diseases, primarily of the hepatobiliary system. The article presents the results of clinical and experimental studies revealing the pathogenetic connections of GERD and hepatobiliary pathology accompanied by biliary dyskinesia, factors leading to an impairment of the duodenal propulsive activity. It is noted that the most important components of the esophageal mucosa lesion in duodenogastroesophageal reflux are bile acids, lysolecithin and pancreatic enzymes. The relevance of prescribing drugs that can affect the course of pathogenetically related diseases, which can significantly reduce the risk of polypragmasia, is justified. Such drugs include ursodeoxycholic acid, which, in the conditions of the GERD and hepatobiliary pathology association, contributes to the functional state normalization of the liver and biliary tract, reduces biliary dyskinesia, the severity of duodenal hypertension and duodenogastroesophageal reflux. The next example is the rebamipide cytoprotector, which has a multilateral protective effect against the mucous membrane of the GIT, including the esophagus, gastroduodenal zone, small intestine, as well as liver. The expediency of prescribing rebamipide to patients who are refractory to therapy with proton pump inhibitors is justified. KEYWORDS: comorbidity, hepatobiliary pathology, gastroesophageal reflux disease, ursodeoxycholic acid, rebamipid, proton pump inhibitors. FOR CITATION: Kazyulin A.N., Goncharenko A.Yu., Kalyagin I.E. Association of hepatobiliary pathology and gastroesophageal reflux disease. Russian Medical Inquiry. 2021;5(6):404–412 (in Russ.). DOI: 10.32364/2587-6821-2021-5-6-404-412.

Comparison of Esophageal Mucosa Protective Efficacy of Evodiae Fructus and Toosendan Fructus against Duodenogastroesophageal Reflux Esophagitis

Background: Gastroesophageal reflux disease accounts for more than 20% of the Western population and is a disease that is also increasing in incidence in Asian countries. Objectives: This work was aimed to assess the impact of Evodiae Fructus and Toosendan Fructus against esophageal mucosal injury with Duodenogastroesophageal Reflux Esophagitis (DGER). Materials and Methods: After inducing DGER through surgery, the group was separated (n = 8) and the drug was administered for 2 weeks: normal rats (Normal), Water-treated DGER (Control), Evodiae Fructus 200 mg/kg-treated DGER (EF), and Toosendan Fructus 200 mg/kg-treated DGER (TF). Results: The administration of EF and TF significantly protected the esophageal mucosa. Furthermore, the content of bilirubin, glutamate oxaloacetate transaminase, and glutamate pyruvate transaminase in serum decreased in EF and TF. In addition, those significantly regulated the protein expression of Janus kinase (JAK)/signal transducer and activator of transcription (STAT), AP-1/MAPK, mtrix metalloproteinase (MMP)/tissue inhibitor of metalloproteinase (TIMP), and tight junction. Conclusion: Taken together, the administration of EF and TF significantly protected the esophageal mucosa of reflux esophagitis, and in particular, the esophageal mucosa protective effect was better in EF. Furthermore, EF and TF inhibited the JAK/STAT and AP-1/MAPK pathway, and EF significantly modulated the expression of MMP/TIMP. These results show the potential of EF as a material for DGER by alleviating inflammation and improving esophageal function.

Covering the Cover

Covering the Cover

Gastroesophageal Reflux Poses a Potential Risk for Late Complications of Bronchopulmonary Dysplasia: A Prospective Cohort Study

Bronchopulmonary dysplasia (BPD) is the most common respiratory disorder in extremely low birth weight infants. Although most symptoms of BPD improve, some late complications exist, even with regular treatment. Gastroesophageal reflux (GER), also common in extremely premature infants, may be related to many cardiorespiratory symptoms. However, the potential of GER as a risk factor for late complications associated with BPD is still unclear. The goal of this study was to determine if GER increases the risk of late complications of BPD in infants. A multicenter prospective cohort of 131 infants (79 male subjects, 52 female subjects) with BPD was enrolled. The development of late complications was assessed over an 18-month follow-up period. Twenty-four-hour pH-multichannel intraluminal impedance and gastric sodium concentrations were analyzed in all infants at 36weeks' postmenstrual age and at the last interview. Prevalence and risk factors of late complications of BPD were analyzed by using forward logistic regression. The prevalence of late complications in BPD infants was 63.79%and included respiratory symptoms (49.14%), vomiting (38.79%), retinopathy of prematurity (25.86%), hypoxic-ischemic injury (3.45%), rehospitalization (26.72%), and sudden death (0.86%). Respiratory diseases constituted the most frequent complication. The prevalence of GER in BPD was 42.24%and included acid GER (18.10%) and duodenogastroesophageal reflux (DGER; 24.14%). Risk factors for respiratory symptoms were gestational age≤ 30weeks (OR, 3.213; 95%CI, 1.221-8.460), birth weight< 1,500g (OR, 2.803; 95%CI, 1.014-7.749), invasive ventilation > 7days (OR, 4.952; 95%CI, 1.508-16.267), acid GER (OR, 4.630; 95%CI, 1.305-16.420), and DGER (OR, 5.588; 95%CI, 1.770-17.648). Infants with BPD and DGER were more prone to late complications than those with acid GER or no reflux. The prevalence of late complications is high in infants with BPD. GER (and in particular, DGER) poses a tentative risk for these late complications. ClinicalTrials.gov; No.: NCT03014453; URL: www.clinicaltrials.gov.