In vitro model for gastroduodenal reflux-induced nuclear factor-kappaB activation and its role in hypopharyngeal carcinogenesis.

BACKGROUND: The purpose of this study was to investigate whether gastroduodenal reflux can play a role in the pathogenesis of hypopharyngeal cancer; therefore, we assessed its effect on the nuclear factor-kappa B (NF-κB) pathway, as similarly noted in the esophagus. METHODS: We exposed human cells derived from the hypopharyngeal epithelium to bile acids or deoxycholic acid. We centered our study on the transcriptional activation of NF-κB pathway, previously linked to head and neck squamous cell carcinoma (HNSCC). RESULTS: We show that acidic-bile salts induce: (1) NF-κB activation with high cytoplasmic Bcl-2 expression; (2) significant increase in expression v-rel avian reticuloendotheliosis viral oncogene homolog A (RELA(p65)), v-rel avian reticuloendotheliosis viral oncogene homolog (c-REL) signal transducer and activator of transcription 3 (STAT3), isoform of transformation related protein p63 (ΔNp63), B-cell lymphoma 2 (Bcl-2), tumor necrosis factor alpha (TNF-α), epidermal growth factor receptor (EGFR), and wingless type MMTV integration site family member 5A (WNT5A) and a decrease in tumor protein p53 (Tp53); and (3) phenotypic changes that are similar to the phenotype of the untreated hypopharyngeal cancer cell line, University of Michigan squamous cell carcinoma (UMSCC)-11B. These changes are not seen when cells were exposed to neutral control or acid alone. CONCLUSION: Our findings in vitro are consistent with the hypothesis that gastroduodenal reflux plays a role in hypopharyngeal carcinogenesis and its effect is mediated through activation of NF-κB pathway. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1381-E1391, 2016.

[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.

[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.

[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.

Automatic motion analysis system for pyloric flow in ultrasonic videos.

Ultrasonography has been widely used to evaluate duodenogastric reflux (DGR). But to the best of our knowledge, no automatic analysis system was developed to realize the quantitative computer-aided analysis. In this paper, we propose a system to perform the automatic detection of DGR in the ultrasonic image sequences by applying the automatic motion analysis. The motion field is estimated based on image velocimetry. Then, an intelligent motion analysis is applied. For the DGR detection, the motion and structural information is combined to analyze the transploric motion of the fluid. In order to test the performance of the proposed system, we designed the experiment with the real and synthetic ultrasonic data. The proposed system achieved a good performance in the DGR detection. The automatic results were accordant with the gold standard in analyzing the fluid motion. The proposed system is supposed to be a promising tool for the study and evaluation of DGR.

[The clinical and pathogenetic types of gastroesophageal reflux disease: risk factors and predictors].

AIM: To study the clinical and pathogenetic types of gastroesophageal reflux disease (GERD) in terms of different types of reflux into the esophagus, their risk factors and predictors. MATERIALS AND METHODS: The clinical, morphological, motor tonic characteristics of the esophagogastroduodenal area, the phenotypic and visceral signs of existing undifferentiated connective tissue dysplasias (UDCTD), and the suprasegmental and segmental autonomic apparatus were studied in detail in 124 patients with GERD. RESULTS: Two clinical and pathogenetic types of GERD associated with the predominance of gastroesophageal or duodenogastroesophageal refluxes (GER and DGER) are identified. The type of the disease running in the predominance of GER develops in subjects with the high rate of visceral stigmas of UDCTD--cardiac failure and hiatal hernias, sympathetic autonomic tone in the digestive system. The feeding preference of piquant and spicy dishes and spices serves to realize the predictors of this type. The DGER-associated type develops in subjects with a concurrence of sympathetic and parasympathetic total autonomic tones in the digestive system in the presence of preexisting biliary tract diseases, including abnormalities in the structure of the gallbladder as visceral signs of UDCTD and it is realized in the feeding preference of high-calorie dishes. CONCLUSION: It is promising to study the autonomic status and the signs of UDCTD as structural and functional predictors of GERD and its types for the prediction of the disease, professional orientation, and the acquisition of eating behavior primarily in young people.

Weighted cross-correlation based variational optical flow for gastric flow analysis in ultrasonic videos.

PURPOSE: Estimating the fluid motion in ultrasonic videos is a crucial step in the analysis of duodenogastric reflux. Severe image noise and illumination changes in the pyloric region (the region of interest) challenge the accurate estimation of gastric flow. In this paper, the authors propose an illumination-robust optical flow method based on the weighted cross-correlation. METHODS: Cross-correlation was combined with the variational optical method framework as an illumination-robust local feature identifier. In consideration of accuracy near edges, they constructed visual similarity weights according to the characteristics of ultrasonic images. A processing procedure containing coarse-to-fine step and refinement was designed to get the final results. They tested the proposed method on synthetic and real ultrasonic images and compared it with other three optical flow methods. For quantitative evaluation, two metrics of angular and amplitude error were used. RESULTS: The synthetic results demonstrate that the proposed method performs better on ultrasonic images, with angular error of 4.1° and amplitude error of 3.3%. In qualitative comparison, the proposed method kept the motion field smooth in the homogeneous region while preserving edge information. When they used the results of the proposed method to judge the gastric flow direction, the automatic judgments agreed well with visual observation. CONCLUSIONS: The proposed method is a good tool for image velocimetry in ultrasonic images. It provides promising results to estimate the motion of gastric flow in ultrasonic videos.

Anti-reflux surgery for lung transplant recipients in the presence of impedance-detected duodenogastroesophageal reflux and bronchiolitis obliterans syndrome: a study of efficacy and safety.

BACKGROUND: The aim of this study was to determine the safety of anti-reflux surgery for lung transplant recipients and assess its effect on lung function. METHODS: We retrospectively collected and analyzed data from all lung transplant recipients who underwent anti-reflux surgery at St Mary's Hospital London from July 2005 to May 2012. The indications for surgery were histologic evidence of gastroesophageal reflux aspiration on bronchoscopy biopsy specimens or a positive impedance study with symptomatic reflux or a consistent decline/fluctuating forced expiratory volume in 1 second (FEV(1)). We studied the difference in mean FEV(1) and rate of change of FEV(1), before and after fundoplication. The safety of anti-reflux surgery was determined by post-operative morbidity and mortality and compared with predicted figures, using a risk prediction model based on the P-POSSUM (Portsmouth Modification of the Physiological and Operative Severity Score for Enumeration of Mortality and Morbidity) assessment. RESULTS: Forty patients underwent laparoscopic Nissen fundoplication. Overall, mean FEV(1) declined from 2119 ± 890 to 1967 ± 1027 ml (p = 0.027), and mean rate of change in FEV(1) improved from -2.42 ± 4.40 to -0.41 ± 1.77 ml/day (p = 0.007). Patients referred for fundoplication based on histologic evidence of reflux (n = 9) showed an improvement in rate of change of FEV(1) from -3.39 ± 6.00 to -0.17 ± 1.50 ml/day (p = 0.057), and those with positive impedance study and consistent decline in FEV(1) (n = 13) showed a significant improvement from -3.62 ± 3.35 to -0.74 ± 2.33 ml (p = 0.021). Actual and predicted morbidity was 2.5% and 31%, respectively. Actual and predicted 30-day mortality was 0% and 1.9%, respectively. CONCLUSIONS: Anti-reflux surgery is safe for lung transplant recipients and results in an improvement in the rate of change in FEV(1) despite a decline in mean FEV(1) post-operatively.

Transposed intrathoracic stomach: functional evaluation.

BACKGROUND: To study the functional aspects of the transposed stomach in the thoracic cavity and its effects on other organ systems. PATIENTS AND METHODS: Children who had undergone gastric transposition more than 5 years ago were evaluated for symptoms, anthropometry, anaemia, duodenogastric reflux, pulmonary function, gastric emptying, gastric pH, gastroesophageal reflux and stricture, gastric motility, and gastritis and atrophy on histological examination of gastric mucosa. RESULTS: Ten children were evaluated at a median follow-up of 90.5 months. On evaluation of symptoms, nine children were satisfied with the overall outcome. All patients had their weight and 7 patients had height less than 3 rd percentile for their respective age. Anaemia was present in 7/10 children. On evaluation with hepatobiliary scintigraphy, duodenogastric reflux was present in only 1 patient. Mass contractions of the transposed stomach were present in two thirds of the children. The mean gastric emptying t1/2 was 39.1 minutes. Pulmonary function tests were suggestive of restrictive lung disease in all the patients. Forced vital capacity (FVC) and forced expiratory volume in 1 sec (FEV1) were worse in children who underwent transposition or diversion following oesophageal anastomotic leak. Acid secretion was preserved in most patients with episodes of high gastric pH during sleep in nearly half. Mild gastritis was present in all patients where as mild atrophy of the gastric mucosa was observed in only 1child. Helicobacter pylori were positive in 3/ 8 children. Barium swallow demonstrated reflux in 2 children. CONCLUSIONS: Most children with transposed stomach remain asymptomatic on follow up. However, subclinical abnormalities are detected on investigations, which need close observation as they can manifest later in life.

The role of total bile acid in oral secretions in ventilator-associated pneumonia.

PURPOSE: The aim of this study was to investigate the role of inflammatory biomarkers and total bile acid (TBA) in oral secretions in the development of ventilator-associated pneumonia (VAP). MATERIALS: This prospective study was conducted in an intensive care unit. Oral secretions were collected from mechanically ventilated patients who met the selection criteria for VAP prevention protocol. The levels of interleukin (IL)-1ß, IL-6, IL-8, tumor necrosis factor α, soluble intercellular adhesion molecule-1, monocyte chemoattractant protein-1, C-reactive protein, surfactant protein D, and TBA in oral secretions were measured and compared between the patients with and those without VAP. RESULTS: Thirty-nine patients with and 39 patients without VAP were studied. The levels of inflammatory biomarkers in oral secretions showed no significant difference between the 2 groups. However, the patients with VAP had significantly higher values of TBA in oral secretions than did those without VAP (median and 25th-75th interquartile range, 9.59 and 1.37-24.66 µmol/L vs 2.74 and 0.00-8.22 µmol/L; P < .003). No significant correlations were found between TBA and inflammatory biomarkers in oral secretions. CONCLUSIONS: Duodenogastroesophageal reflux as evidenced by the presence of TBA in oral secretions is common in mechanically ventilated patients and may play a role in the development of VAP.

Acid suppression increases rates of Barrett's esophagus and esophageal injury in the presence of duodenal reflux.

BACKGROUND: The contribution of gastric acid to the toxicity of alkaline duodenal refluxate on the esophageal mucosa is unclear. This study compared the effect of duodenal refluxate when acid was present, decreased by proton pump inhibitors (PPI), or absent. METHODS: We randomized 136 Sprague-Dawley rats into 4 groups: group 1 (n = 33) were controls; group 2 (n = 34) underwent esophagoduodenostomy promoting "combined reflux"; group 3 (n = 34) underwent esophagoduodenostomy and PPI treatment to decrease acid reflux; and group 4, the 'gastrectomy' group (n = 35) underwent esophagoduodenostomy and total gastrectomy to eliminate acid in the refluxate. Esophaguses were examined for inflammatory, Barrett's, and other histologic changes, and expression of proliferative markers Ki-67, proliferating cell nuclear antigen (PCNA), and epidermal growth factor receptor (EGFR). RESULTS: In all reflux groups, the incidence of Barrett's mucosa was greater when acid was suppressed (group C, 62%; group D, 71%) than when not suppressed (group B, 27%; P = 0.004 and P < .001). Erosions were more frequent in the PPI and gastrectomy groups than in the combined reflux group. Edema (wet weight) and ulceration was more frequent in the gastrectomy than in the combined reflux group. Acute inflammatory changes were infrequent in the PPI group (8%) compared with the combined reflux (94%) or gastrectomy (100%) groups, but chronic inflammation persisted in 100% of the PPI group. EGFR levels were greater in the PPI compared with the combined reflux group (P = .04). Ki-67, PCNA, and combined marker scores were greater in the gastrectomy compared with the combined reflux group (P = .006, P = .14, and P < .001). CONCLUSION: Gastric acid suppression in the presence of duodenal refluxate caused increased rates of inflammatory changes, intestinal metaplasia, and molecular proliferative activity. PPIs suppressed acute inflammatory changes only, whereas chronic inflammatory changes persisted.

[Disturbances of gastrointestinal motility of the stomach in patients with chronic gastric erosions and biliary tract disease].

Article dwells on comparison data about motor function of the stomach in the three groups of patients: with gastric erosions and biliary tract diseases, duodenal ulcer disease, chronic gastritis. It is shown, that patients with gastric erosions and biliary tract diseases are characterized by slower evacuation function of the stomach, hypotonus of the stomach. Frequency of duodenal reflux in this group of patients is very high (85,9 %).

[Diagnostic aspects of chronic cholangitis after cholecystectomy].

AIM: To determine the chronic cholangitis risk factors and to provide a practically significant diagnostic criteria of chronic cholangitis in patients after cholecystectomy. MATERIALS AND METHODS: Were examined the clinical, anamnestic data, clinical laboratory and instrumental studies of the condition of the hepatobiliary system in 127 patients with chronic cholangitis after cholecystectomy. The determination of microbial contamination of bile was performed during the duodenal intubation. RESULTS: In the bile microbial landscape study were noted the violation of biliary system microbiota in 92.1% of cases. Herewith identified a combination of bacterial factors with parasitic invasion (mixed infection) in 28 (22.0%) patients. Cholangitis develops in the presence of duodeno biliary reflux, duodenal motility disorders and hypotonia of Oddi's sphincter in the early postoperative period. In the late periods after cholecystectomy, cholangitis chronization defines outflow obstruction and cholestasis due to functional or organic causes in most patients. CONCLUSIONS: Risk factors for chronic cholangitis should be referred to long history of gallstone disease, performance of cholecystectomy in the emergency order against the inflammatory process of thehepatobiliary system, absence of adequate correction of postoperative hypertension of bile duct, destruction of sphincter apparatus major duodenal papilla during surgery.

Gastric emptying and different types of reflux in adult patients with cystic fibrosis.

BACKGROUND: Increased gastro-oesophageal reflux (GER) is common in patients with cystic fibrosis (CF). Previous studies showed delayed gastric emptying (GE) and a high prevalence of bile acids in saliva suggesting duodenogastro-oesophageal reflux (DGER). AIM: To assess different types of reflux (acid, weakly acidic and bile) and their relationship with rate of GE in adult CF patients. METHODS: Gastric emptying was assessed in 33 CF patients using breath tests, reflux was monitored in 42 patients using impedance-pH-metry and 14 CF patients underwent combined impedance-pH-Bilitec monitoring. RESULTS: Delayed GE was found in 33%, increased GER (predominantly acid) in 67% and pathological DGER in 35% of the CF patients. There was a significant correlation between oesophageal bile and acid exposure (P < 0.0001, r = 0.85). Patients with increased DGER had a higher proximal extent of reflux compared to those without DGER [17 (9-35) vs. 5 (1-12), P = 0.04]. There was no correlation between GE and reflux parameters, however, in a subgroup of 10 patients studied by impedance-pH-Bilitec and GE, there was a strong correlation between GE rate and bile exposure (P = 0.005, r = 0.83). CONCLUSIONS: Delayed gastric emptying is present in 1/3 of patients with cystic fibrosis. There is a subgroup of these patients with both delayed gastric emptying and increased acidic duodenogastro-oesophageal reflux with high proximal extent and risk of aspiration. Controlled studies should be performed to evaluate the effect of prokinetics or antireflux surgery on the clinical cystic fibrosis evolution in these patients.

[Clinico-endoscopic peculiarities of gastric ulcer of type I and II].

A detailed analysis of clinico-endoscopic peculiarities of gastric ulcer type I and II was presented. The peculiarities of a clinical course and the complications character of differently localized gastric ulcers were determined. There was shown the connection between concomitant disorders of esophagogastroduodenal motor-evacuation function and gastric ulcer localization and type. While tactics of treatment and operative procedure choosing it is mandatory to take into account the clinical course peculiarities and the results of endoscopic investigation.

What influences the acidity in the gastric conduit in patients who underwent cervical esophagogastrostomy for cancer?

The aim of this study was to determine the factors influencing acidity in the gastric conduit after esophagectomy for cancer. Acidity and bile reflux in the stomach and in the gastric conduit were examined by 24-h pH monitoring and bilimetry in 40 patients who underwent transthoracic subtotal esophagectomy followed by esophageal reconstruction using a gastric conduit, which was pulled up to the neck through a posterior mediastinal route in 17 patients, through a retrosternal route in 10 patients, and through a subcutaneous route in 13 patients. They were examined at 1 week before surgery, at 1 month after surgery, and at 1 year after surgery. Helicobacter pylori infection was examined pathologically and using the (13) C-urea breath test. The factors influencing acidity of the gastric conduit were analyzed using the stepwise regression model. Gastric acidity assessed by percentage (%) time of pH < 4 was reduced after surgery and was significantly less in patients with H. pylori infection compared with those without H. pylori infection throughout the period from 1 week before surgery to 1 year after surgery. Duodenogastric reflux (DGR) assessed by % time absorbance > 0.14 into the lower portion of the gastric conduit was significantly increased after surgery throughout the period from 1 month after surgery to 1 year after surgery. Multivariate analysis showed that the acidity in the gastric conduit was influenced by H. pylori infection and DGR at 1 month after surgery, and by H. pylori infection and the route for esophageal reconstruction at 1 year after surgery. Acidity in the gastric conduit was significantly decreased after surgery. Acidity in the gastric conduit for esophageal substitutes is influenced by H. pylori infection and surgery. DGR influences the gastric acidity in the short-term after surgery, but not in the long-term after surgery.

[Dysmotility-type dyspepsia and eructation. Introduction of a new gas-analytical method]. / Dysmotilitas típusú dyspepsia és bélgázok. Új gázanalitikai módszer bemutatása.

This paper describes a new gas-analytical method used in a 55-year-old female patient with dyspepsia. Symptoms included epigastric fullness and inflation. Evaluation indicated an increased gas production in the proximal end of the small intestine that entered into the stomach via duodenogastric reflux. High CO2 content of eructed gas was confirmed in eructed gas samples using a tube in situ. Authors propose that this new analytical method of eructed gas may be applied in clinical practice in patients with dyspepsia.

Sphincter of Oddi manometry by choledochoscope in patients with duodenobiliary reflux.

BACKGROUND AND AIM: Previous research has confirmed that duodenobiliary reflux exists in patients with choledocholithiasis. The objective of this study was to investigate whether the motor activity of the sphincter of Oddi (SO) has an effect on duodenobiliary reflux. METHODS: A total of 51 patients orally ingested 1mL water containing technetium-99m diethylenetriaminepentaacetatic acid, and a 2-h bile collection was obtained from the T tube. Technetium counts in the collected bile were performed using an RM905 radioactivity meter. The patients were divided into two groups: reflux group (duodenobiliary reflux positive) and control group (duodenobiliary reflux negative). Next, 33 cases were randomly selected and double blinded to receive SO manometry by choledochoscope. RESULTS: Of the 51 total cases, 16 bile samples exhibited radioactivity. The average SO basal pressure and contraction pressure values were 7.2±3.9mmHg and 53.5±24.5mmHg, respectively, in the reflux group, and 14.7±11.0mmHg and 117.2±65.6mmHg, respectively, in the control group. The choledochus pressure values were 5.1±1.6mmHg and 11.5±7.4mmHg in the reflux group and the control group, respectively. The differences between the groups were statistically significant; however, the SO contraction frequency, SO contraction duration, and duodenum pressure values were not significantly different between the groups. CONCLUSION: The decreases in the SO basal pressure and SO contraction pressure, and the decrease in choledochus pressure, might play a role in duodenobiliary reflux.

[Duodenogastral reflux burden gastroesophageal reflux disease].

The article presents research data of duodenogastral reflux (DGR) role in patients with gastroesophageal reflux disease. It is shown that in the presence DGR, the reflux esophagitis is detected at a higher frequency and outside of esophageal manifestations of the disease. The comorbidities of hepatobiliary zone and pancreas contributes to the DGR development, as well as the syndrome of bacterial overgrowth in the small intestine.

[Morphological features and esophago-gastroduodenal zone microbiocenose in patients with syndrome postcholecystectomic syndrome].

Endoscopical and histological features of oesophagogastroduodenal zone, parameters of pH-metry and electrogastroenterography, qualitative and quantitative characteristics of microbiocenosis were studied in 80 female persons with postcholecystectomy syndrome more then a year after cholecystectomy. In the presence of duodenogastral reflux the most natural is the combination of distal oesophagitis, antral atrophic gastritis and duodenitis, accompanied with low level of gastric acidity, gastric hypokinesis and duodenal dyskinesis, dysbacteriosis of mucosal microflora with its quantitative increase and appearance of bacteria with expressed pathogenicity non-typical for this biotope. These data should be taken into consideration for determination of pre- and postoperative treatment tactics for patients with gallstones.