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

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: The Bil mode can detect bilirubin with high accuracy and could be used to evaluate DGER in clinical practice.

[Impact of primary duodenogastric reflux and Helicobacter pylori infection on gastritis and antibiotic resistance in children]. / å„¿ç«¥åŽŸå‘æ€§åäºŒæŒ‡è‚ èƒƒåæµä¸Žå¹½é—¨èžºæ†èŒæ„ŸæŸ“å¯¹èƒƒç‚Žå’ŒæŠ—ç”Ÿç´ è€è¯æ€§çš„å½±å“.

OBJECTIVES: To investigate the risk factors for Helicobacter pylori (HP) infection in children with primary duodenogastric reflux (DGR) and its impact on gastritis and antibioticresistance. METHODS: A retrospective analysis was performed on the clinical data of 2 190 children who underwent upper gastrointestinal endoscopy in Wuxi Children's Hospital from January 2019 to February 2022, among whom 308 children were diagnosed with primary DGR. According to the presence or absence of HP infection, the children were classified to HP infection group (53 children) and non-HP infection group (255 children). The risk factors for HP infection and its impact on the incidence rate and severity of gastritis were analyzed. According to the presence or absence of primary DGR, 331 children with HP infection were classified to primary DGR group (29 children) and non-primary DGR group (302 children), and then the impact of primary DGR with HP infection on antibiotic resistance was analyzed. RESULTS: The HP infection group had a significantly higher age than the non-HP infection group (P<0.05), and there was a significant difference in the age distribution between the two groups (P<0.05), while there were no significant differences in the incidence rate and severity of gastritis between the two groups (P>0.05). The multivariate logistic regression analysis showed that older age was a risk factor for HP infection in children with DGR (P<0.05). Drug sensitivity test showed that there were no significant differences in the single and combined resistance rates of metronidazole, clarithromycin, and levofloxacin between the primary DGR group and the non-primary DGR group (P>0.05). CONCLUSIONS: Older age is closely associated with HP infection in children with DGR. Primary DGR with HP infection has no significant impact on gastritis and antibiotic resistance in children.

Gastroparesis Worsens Indomethacin-Induced Gastric Antral Ulcers by Bile Reflux via Activation of 5-HT3 and Dopamine D2 Receptors in Mice.

BACKGROUND/AIMS: We examined the contributions of gastric emptying and duodenogastric bile reflux in the formation of gastric antral ulcers induced by NSAIDs in mice. METHODS: We used the murine re-fed indomethacin (IND) experimental ulcer model. Outcome measures included the appearance of gastric lesions 24 h after IND treatment and the assessment of gastric contents and the concentration of bile acids 1.5 h after re-feeding. The effects of atropine, dopamine, SR57227 (5-HT3 receptor agonist), apomorphine, ondansetron, haloperidol, and dietary taurocholate and cholestyramine were also examined. RESULTS: IND (10 mg/kg, s.c.) induced severe lesions only in the gastric antrum in the re-fed model. The antral lesion index and the amount of food intake during the 2-h refeeding period were positively correlated. Atropine and dopamine delayed gastric emptying, increased bile reflux, and worsened IND-induced antral lesions. SR57227 and apomorphine worsened antral lesions with increased bile reflux. These effects were prevented by the anti-emetic drugs ondansetron and haloperidol, respectively. The anti-emetic drugs markedly decreased the severity of antral lesions and the increase of bile reflux induced by atropine or dopamine without affecting delayed gastric emptying. Antral lesions induced by IND were increased by dietary taurocholate but decreased by the addition of the bile acid sequestrant cholestyramine. CONCLUSIONS: These results suggest that gastroparesis induced by atropine or dopamine worsens NSAID-induced gastric antral ulcers by increasing duodenogastric bile reflux via activation of 5-HT3 and dopamine D2 receptors.

[Cholecystectomy as a risk factor for duodenogastric reflux]. / Colecistectomía como factor de riesgo para reflujo duodenogástrico.

Bile reflux or duodenogastric reflux (DGR), refers to the retrograde flow of duodenal contents (mainly bile) into the stomach; capable of producing chemical damage to the mucosa, and triggering mutations towards the development of intestinal metaplasia, dysplasia and even gastric cancer. OBJECTIVE: This study aimed to estimate the prevalence of primary bile reflux in cholecystectomized patients and to identify whether cholecystectomy is a risk factor for development of DGR. MATERIALS AND METHODS: An analytical cross-sectional and observational study was conducted, in which all patients who underwent upper digestive endoscopy from February to June 2023 in a private endoscopic center in Lima, Peru, were included. According to the endoscopic report, patients were divided into two groups as those with DGR and those without DGR. Demographic characteristics, history of cholecystectomy, and endoscopic findings were statistically analyzed. 408 patients were included. RESULTS: The mean age of the population was 48.18 ± 16.82 years; 61.52% were female. The prevalence of DGR was 25.74% in the population, while in cholecystectomized patients it was 52.11%. The prevalence of DRG in patients with a history of cholecystectomy was 2.58 times compared to patients without cholecystectomy (p<0.001). Age ≥50 years also behaved as a risk factor for RDG (p=0.025). No significant difference in diabetes, Helicobacter pylori infection or smoking were found. CONCLUSION: In conclusion, a history of cholecystectomy as well as age were found to be risk factors for development of primary DGR.

The Relationship between Primary Duodenogastric Reflux and Helicobacter pylori Gastritis in Children.

BACKGROUND: Most studies of the relationship between duodenogastric reflux (DGR) and Helicobacter pylori have reported that the presence of DGR decreases H. pylori colonization, while H. pylori infection increases the frequency of DGR by impairing antroduodenal motility. The present study aimed to investigate the relationship between primary DGR and the prevalence of H. pylori in children, as well as the degree of colonization and the presence and severity of gastritis. METHODS: Included in the study were 410 patients between the ages of 2 and 18 years, referred to the pediatric gastroenterology clinic with complaints of dyspepsia, abdominal pain, and nausea/vomiting, who underwent upper gastrointestinal system endoscopic examination and stomach biopsy. The study group included 60 patients with DGR, while 350 non-DGR patients formed the control group. RESULTS: The mean age of patients with DGR was 15.7 ± 2.1 years, while the mean age of the control group was 14.2 ± 3.8 years (p = 0.02). Of those with DGR, 50 (83.3%) were girls, while in the control group, 215 (61.4%) were girls (p = 0.001). Of patients with DGR, 16 were H. pylori (+) (26.7%), while in the control group, 168 were H. pylori (+) (48%) (p = 0.002). There was no significant difference between the 2 groups with respect to H. pylori degree of colonization (p = 0.08). Gastritis was present in 56 (93.3%) patients in the DGR group and 322 (92%) patients in the control group (p = 0.72). A significant difference was found between the 2 groups in terms of gastritis severity (p = 0.01). CONCLUSIONS: The mean age of patients with DGR was significantly higher than that of patients without DGR, and DGR was found to be more common in girls. In patients with DGR, H. pylori prevalence was significantly lower than in those without DGR; however, no significant difference was found between the 2 groups with respect to the colonization degree.

Theoretical modeling of the resistance to gastric emptying and duodenogastric reflux due to pyloric motility alone, presuming antral and duodenal quiescence.

A theoretical model of the pyloric channel, approximated as a two-dimensional tube with sinusoidal corrugation, is developed to estimate the degree of resistance offered by the pylorus to transpyloric flow (gastric emptying and duodenogastric reflux) in the viscous regime. Study indicates that the resistance of the channel depends on pressure gradient, flow behavior index and channel diameter. Flow is majorly determined by the extent of luminal opening; since they scale to fourth power of the diameter for Newtonian flow, with the exponent being higher for pseudoplastic and lesser in case of dilatants relative to Newtonian fluid. At zero pressure difference, across the channel, the closing pylorus drives the aborad propulsion of the contents at the intestinal end, and at the gastric end the flow is driven along the orad direction. While no transfer of contents occur at the centre of pylorus due to zero pressure gradients, it is essential to have a non-zero pressure difference to drive the flow through the channel. The extent of pressure difference is found to linearly relate to the transpyloric flow rate. The resistive function of the pyloric channel is observed at a higher occlusion where there is a development of higher pressure barrier that is sensitive to the flow behavior index, frequency, occlusion, and contraction length.

Development of Pancreatic Acinar Cell Metaplasia During Gastric Repair in a Rat Duodenal Contents Reflux Model.

BACKGROUND: We previously reported the development of pancreatic acinar cell metaplasia (PACM) in the glandular stomach of a duodenal contents reflux model (reflux model). AIMS: We aimed to investigate the characteristics and histogenesis of PACM using a reflux model. METHODS: A reflux model was created using 8-week-old male Wistar rats, which were killed up to 30 weeks postoperatively. Histological examination was performed to analyze the glandular stomach-jejunal anastomosis. Furthermore, electron microscopic images of PACM samples were compared with pancreatic and gastric glands removed from rats that had not undergone surgery. Immunostaining for α-amylase, HIK1083, TFF2, and Ki-67 was performed, and double fluorescent staining was carried out using antibodies against α-amylase and HIK1083, or α-amylase and TFF2. RESULTS: In all reflux model rats, PACM was observed proximal to the glandular stomach-jejunal anastomosis, surrounded by pseudopyloric metaplasia. The number of chief cells was decreased in the deep part of the gland, where PACM occurred. Electron microscopy showed that PACM cells had greater numbers of rough endoplasmic reticulum tubules than chief cells, and exhibited pancreatic acinar cell morphology. Upon immunochemical staining, the regenerative foveolar epithelium and part of the pseudopyloric glands stained strongly positive for TFF2, whereas PACM cells were only weakly positive. Double fluorescent staining identified early lesions of PACM in the neck, which were double positive for α-amylase and TFF2, but negative for HIK1083. CONCLUSIONS: PACM could be induced by duodenal contents reflux. PACM originates from stem cells located in the neck of oxyntic glands during gastric mucosal regeneration.

Columnar epithelium morphology after esophagectomy: clinical insight into the development of Barrett's esophagus.

BACKGROUND: The presence of Barrett's mucosa in the esophageal remnant is a result of post-esophagectomy anastomotic site exposure to gastric acid and is regarded as a human model of Barrett's esophagus onset. Here, we attempted to clarify the relationship between duodenogastric reflux and formation of columnar epithelium by following the changes over time after esophagectomy. METHODS: A total of 96 patients underwent esophagectomy due to superficial cancer from April 2000 to March 2018 were included in this study. Cases were divided into two groups according to the reconstruction technique after esophagectomy as either the gastric pull-up (Ga) group and ileocolonic interposition (Ic) group. Previously obtained endoscopic pictures of the cases were reviewed retrospectively and chronologically. RESULTS: There were 24 cases of columnar epithelium in the Ga group (42%) and 1 in the Ic group (2.6%) (P < 0.01) with 32 reflux cases (56%) in the Ga group and 1 (2.6%) in the Ic group (P < 0.01). Reflux precedes the development of columnar epithelium in both the Ga- and Ic groups. Multivariate analysis revealed surgical technique (odds ratio 10.6, 95% CI 1.2-97.5, P = 0.037) and reflux (odds ratio 4.5, 95% CI 1.3-15.6, P = 0.0017) as risk factors. CONCLUSIONS: The development of columnar epithelium was preceded by reflux comprising principally gastric acid and was strongly associated with a strong inflammatory state.

The Effect of Primary Duodenogastric Bile Reflux on the Presence and Density of Helicobacter pylori and on Gastritis in Childhood.

Background and Objectives: Although there are many studies that investigate the relationship between duodenogastric reflux (DGR) and Helicobacter pylori in adult patients, the reported data are contradictory. In addition, there are very few studies in the literature investigating the relationship between DGR and H.pylori in the pediatric age group. In the present study, we investigated the effect of primary DGR on H.pylori and gastritis. Materials and Methods: A total of 361 patients who were referred to the clinic of our hospital with dyspeptic complaints who had an upper gastrointestinal system endoscopy and a gastric biopsy were included in the study. Results: DGR was detected in 45 cases, and 316 cases that did not have DGR were considered as the control group. Comparisons were made between the DGR cases and the control group in terms of risk factors (age, gender), the presence and density of H.pylori, and the presence and severity of gastritis. The average age of the patients who were included in the study was 11.6 ± 4.6 years. A total of 128 (36%) of the cases were male and 233 (64%) were female. DGR was present in 45 (13%) of the cases. The average age of the patients with DGR was 13.9 ± 3.1 years, the average age of the control group was 11.3 ± 4.7, and there were statistically significant differences (p < 0.001). No significant differences were detected in terms of gender between DGR and the control group (p > 0.05). H.pylori (+) was detected in 29 (64%) of patients with DGR, and in 202 (64%) of the control group. No significant differences were detected between H.pylori prevalence (p = 0.947). Gastritis was detected in 37 (82%) of the patients with DGR, and in 245 (77%) of the control group (p = 0.476). No significant differences were detected between the presence and density of H.pylori, gastritis presence, severity and DGR (p > 0.05). Conclusions: The ages of patients with DGR were significantly higher than in the control group, and advanced age was shown to be a risk factor for primary DGR. It was found that the presence of DGR has no effect on the presence and severity of H.pylori. Given this situation, we consider it is important to eradicate H.pylori infection, especially in the case where H.pylori is present together with DGR.

The Impact of the Location of Esophagogastrostomy on Acid and Duodenogastroesophageal Reflux After Transthoracic Esophagectomy with Gastric Tube Reconstruction and Intrathoracic Esophagogastrostomy.

BACKGROUND: The aim of this study was to evaluate the impact of the location of esophagogastrostomy on acid and duodenogastroesophageal reflux (DGER) in patients undergoing gastric tube reconstruction and intrathoracic esophagogastrostomy. METHODS: Thirty patients receiving transthoracic esophagectomy without cervical lymph node dissection and gastric tube reconstruction by intrathoracic anastomosis were enrolled. All patients underwent 24-h pH and bilirubin monitoring and gastrointestinal endoscopy one year after surgery. Patients were divided into three groups according to esophagogastrostomy location: group A (n = 9), above the top of the aortic arch; group B (n = 15), between the top and bottom of the aortic arch; and group C (n = 6), below the bottom of the aortic arch. The relations among the esophagogastrostomy location, 24-h pH and bilirubin monitoring results, endoscopic findings, and reflux symptoms were investigated. RESULTS: No acid reflux into the remnant esophagus was observed in group A, whereas it was observed in three of 15 patients (20%) in group B and in two of six patients (33%) in group C (P = 0.139). No DGER was found in group A, whereas DGER was observed in eight (53%) patients in group B and all patients in group C (P < 0.001). Reflux esophagitis was observed in one patient (11%) in group A, five patients (33%) in group B, and all patients in group C (P = 0.002). CONCLUSION: In gastric tube reconstruction via intrathoracic anastomosis, esophagogastrostomy should be performed above the top of the aortic arch to prevent postoperative DGER and reduce the incidence of reflux esophagitis.

Hyperinsulinemia Promotes Esophageal Cancer Development in a Surgically-Induced Duodeno-Esophageal Reflux Murine Model.

Hyperinsulinemia could have a role in the growing incidence of esophageal adenocarcinoma (EAC) and its pre-cancerous lesion, Barrett's Esophagus, a possible consequence of Gastro-Esophageal Reflux Disease. Obesity is known to mediate esophageal carcinogenesis through different mechanisms including insulin-resistance leading to hyperinsulinemia, which may mediate cancer progression via the insulin/insulin-like growth factor axis. We used the hyperinsulinemic non-obese FVB/N (Friend leukemia virus B strain) MKR (muscle (M)-IGF1R-lysine (K)-arginine (R) mouse model to evaluate the exclusive role of hyperinsulinemia in the pathogenesis of EAC related to duodeno-esophageal reflux. FVB/N wild-type (WT) and MKR mice underwent jejunum-esophageal anastomosis side-to end with the exclusion of the stomach. Thirty weeks after surgery, the esophagus was processed for histological, immunological and insulin/Insulin-like growth factor 1 (IGF1) signal transduction analyses. Most of the WT mice (63.1%) developed dysplasia, whereas most of the MKR mice (74.3%) developed squamous cell and adenosquamous carcinomas, both expressing Human Epidermal growth factor receptor 2 (HER2). Hyperinsulinemia significantly increased esophageal cancer incidence in the presence of duodenal-reflux. Insulin receptor (IR) and IGF1 receptor (IGF1R) were overexpressed in the hyperinsulinemic condition. IGF1R, through ERK1/2 mitogenic pattern activation, seems to be involved in cancer onset. Hyperinsulinemia-induced IGF1R and HER2 up-regulation could also increase the possibility of forming of IGF1R/HER2 heterodimers to support cell growth/proliferation/progression in esophageal carcinogenesis.

[Biliary reflux-gastritis: etiology, pathogenesis and modern principles of treatment].

Objective. To study etiopathogenetic aspects of biliary reflux-gastritis (RG) and develop modern principles of its therapy depending on acidity of stomach contents, atrophy ofgastric mucosa, and Helicobacter pylori infection. Different pathogenetic mechanisms of RG are discussed with special reference to bile flow into the antrum as a result of duodenogastric reflux. It is shown that the use of de-nol and probiotic ProBiotic Complex for the treatment of biliary reflux-gastritis increases effectiveness of H. pylori eradicationby 18.2% and prevents the development of bowel dysbiosis.

Mechanisms of Discoordination of Contractile Activity in the Gastroduodenal Zone during Psychogenic Stress in Rabbits.

Inhibition of the contractile activity of the stomach induced by psychogenic stress persisted after blockade of muscarinic and nicotinic cholinergic receptors and α2 and ß1/ß2-adrenergic receptors. Stress-induced increase in contractile activity in the proximal part of the duodenum persisted during blockade of muscarinic and nicotinic cholinergic receptors, ß1/ß2-adrenergic receptors. At the same time, blockade of the above cholinergic and adrenergic receptors eliminated the stress-induced increase in contractive activity in the distal part of the duodenum.

[Gastroesophageal reflux disease in patients receiving chemotherapy: clinical, endoscopic, morphological and immunohistochemical features].

THE PURPOSE OF THE STUDY: Determine the pathogenetic significance of express molecules PCNA, Bcl-2, NF-Kb and tachykinins (substance P, neurokinin A) in patients with gastroesophageal reflux disease (GERD), receiving polychemotherapy (PCT). MATERIALS AND METHODS: In total 60 patients were examined with GERD time-divided into 2 equal groups on the receiving PCT Leukemia over standard dose for at least one year. The first group consisted of 30 subjects with non-erosive GERD (NEGERD) endoscopically positive form receiving PCT. The second group consisted of 30 subjects with erosive form of GERD (EFGERD) receiving PCT. Patients underwent endoscopy, morphological and immunohistochemical examination of the esophageal mucosa to the definition expression of molecules PCNA, Bcl-2, neurokinin A, substance P and factor Nf-Kb. In patients with refractory form of GERD to proton pump inhibitors therapy (PPIs), additionally imposed ursodeoxycholic acid. THE RESULTS: Patients with NEGERD receiving PCT in 33.3% of cases formed refractory to PPIs form of the disease, when EFGERD refractoriness occurs in 46.7% of patients, which is associated with slowing the proliferation of epithelial cells of the esophagus due to decreased expression of PCNA. Reduced expression of neurokinin A in patients receiving PCT is associated with less activity and intensity of inflammation of esophageal mucosa. Against the background of a high degree of PCT expression of Bcl-2 and factor Nf-Kb, which may explain the frequent detection of atrophic and meta- plastic changes in the esophageal mucosa. Appointment of ursodeoxycholic acid in the complex therapy of GERD can overcome resistance to PPIs and improve the performance of cell renewal. CONCLUSION: Due to the frequent development of GERD refractory to PPIs in patients suffering from diseases requiring the appointment of long-term courses of PCT requires the appointment of cytoprotective therapy, as that can be used ursodeoxycholic acid.

[DISSEMINATION BY H. PYLORI IN PATIENTS, SUFFERING VARIOUS FORMS OF CHOLECYSTITIS].

Comparative analysis of dissemination by H. pylori of the bile portions in patients of a control group, suffering an acute calculous cholecystitis (ACCH), was performed. Dissemination of H. pylori in a control group was significantly less, than in a bile portions of patients, suffering ACCH. While analyzing the rate and degree of dissemination by H. pylori of the gastic and gallbladder mucosa biopsies of patients, suffering chronic non-calculous cholecystitis, associated with duodenogastric reflux and gastroduodenitis, bacteria were revealed trustworthy more often and in more number, than in a gallbladder mucosa in patients, suffering ACCH.

[APPLICATION OF ILEOCECAL GASTROPLASTY IN EXPERIMENT].

Results of gastroplasty, using ileocecal intestinal segment in experimental animals were presented. Functional state of transplant was estimated using data of angiography, manometry, morphological investigations. In accordance to angiographic data sufficient blood supply of transplant was obtained from a. ileocolica. While manometric and roentgenologic investigations duodenal reflux into small intestine and esophagus was not revealed. Colono-small bowel reflux, determined using hydropression method, was registered in 150 - 170 mm H2O pressure. In accordance to results of morphological investigations in a large bowel reservoir the quantity of goblet cells and the mucus production have enhanced, promoting elimination of inflammation.

[Gastroesophageal reflux disease associated with duodenogastroesophageal reflux in patients with biliary pathology: the specific features of the course and esophagogastroduodenal microbial biocenosis].

AIM: To study the specific features of the clinical course of gastroesophageal reflux disease (GERD) associated with duodenogastroesophageal reflux (DGER) in patients with chronic acalculous cholecystitis (CAC) and cholelithiasis (CL), as well as qualitative and quantitative characteristics. SUBJECTS AND METHODS: The clinical, morphological, motor tonic characteristics of the esophagogastroduodenal area, mucosal microbial biocenosis in the esophagus, stomach, and duodenum were studied in detail in 83 patients with GERD that was associated with DGER and ran concurrently with CAC or CL. RESULTS: Impaired duodenal propulsive activity as a concomitance of the signs of gastrostasis and duodenal dyskinesia with dyscoordination of both anthroduodenal and duodenojejunal propulsion and with the development of duodenogastric reflux and DGER, which in turn determine esophageal and gastric pH values is shown to be of importance in CAC and CL, which match GERD. Abnormal microbiocenosis in the upper digestive tract is characterized by the higher quantitative and qualitative content of the mucous microflora. Opportunistic microorganisms exhibit cytotoxic, hemolytic, lecithinase, caseinolytic, urease, and RNAase activities. CONCLUSION: The found specific features of the course of GERD associated with DGER in patients with biliary tract abnormalities lead us to search for novel therapeutic approaches based on the correction of digestive motor tonic disorders and abnormal microbiocenoses of the mucous flora in the esophagus, stomach, and duodenum.

[Gastroesophageal reflux disease and connective tissue dysplasia in aspect of premorbid and comorbid disorders].

AIM: To investigate the phenotypic and visceral signs of connective tissue dysplasia (CTD) and comorbid diseases of the digestive system in gastroesophageal reflux disease (GERD) patients with different types of esophageal reflux as the predictors of its variants. MATERIAL AND METHODS: In 124 patients with GERD the clinical features, phenotypic and visceral signs of undifferentiated CTD were studied in details. RESULTS: In 82.0% of patients with GERD associated with gastroesophageal type of reflux (GER) phenotypic and especially visceral signs of STD were detected, mainly in the form of cardiochalasia and hiatal hernia. In patients with duodenogastroesophageal reflux symptoms (DGER) the signs of STD were marked in 42.0% of cases, mostly in the form of biliary tract structure abnormalities. The risk of GERD associated with prevalence of GER, was 11.9 times higher in the presence of diagnostically meaningful combination of 6 or more signs of STD than in patients with DGER. Realization of predictor options in GER occurs in the preference of sharp, acidic foods, spices, taking medications that reduce lower esophageal sphincter tone. GERD, associated with DGER, is formed in patients with family history of diseases of the biliary tract and in the preference of food rich of calories. CONCLUSION: Study of STD symptoms as predictors of structural development of GERD and its variants is prospective to predict disease, choice of profession and eating behavior, primarily in young adults.

USP50 regulates NLRP3 inflammasome activation in duodenogastric reflux-induced gastric tumorigenesis.

Duodenogastric reflux (DGR) has been linked to the onset of gastric cancer (GC), although the precise mechanism is yet obscure. Herein, we aimed to investigate how refluxed bile acids (BAs) and macrophages are involved in gastric carcinogenesis. In both active human bile reflux gastritis and the murine DGR model, ubiquitin specific protease 50 (USP50) was dramatically raised, and macrophages were the principal leukocyte subset that upregulated USP50 expression. Enhancing USP50 expression amplified bile acid-induced NLR family pyrin domain containing 3 (NLRP3) inflammasome activation and subsequent high-mobility group box protein 1 (HMGB1) release, while USP50 deficiency resulted in the reversed alteration. Mechanistically, USP50 interacted with and deubiquitinated apoptosis-associated speck-like protein containing CARD (ASC) to activate NLRP3 inflammasome. The release of HMGB1 contributes to gastric tumorigenesis by PI3K/AKT and MAPK/ERK pathways. These results may provide new insights into bile reflux-related gastric carcinogenesis and options for the prevention of DGR-associated GC.