Socioeconomic traits and the risk of Barrett’s esophagus and gastroesophageal reflux disease: A Mendelian randomization study

BACKGROUND Previous observational studies have shown that the prevalence of gastroesophageal reflux disease(GERD)and Barrett’s esophagus(BE)is associated with socioeconomic status.However,due to the methodological limitations of traditional observational studies,it is challenging to definitively establish causality.AIM To explore the causal relationship between the prevalence of these conditions and socioeconomic status using Mendelian randomization(MR).METHODS We initially screened single nucleotide polymorphisms(SNPs)to serve as proxies for eight socioeconomic status phenotypes for univariate MR analysis.The inverse variance weighted(IVW)method was used as the primary analytical method to estimate the causal relationship between the eight socioeconomic status phenotypes and the risk of GERD and BE.We then collected combinations of SNPs as composite proxies for the eight socioeconomic phenotypes to perform multivariate MR(MVMR)analyses based on the IVW MVMR model.Furthermore,a two-step MR mediation analysis was used to examine the potential mediation of the associations by body mass index,major depressive disorder(MDD),smoking,alcohol consumption,and sleep duration.RESULTS The study identified three socioeconomic statuses that had a significant impact on GERD.These included household income[odds ratio(OR):0.46;95% confidence interval(95%CI):0.31-0.70],education attainment(OR:0.23;95%CI:0.18-0.29),and the Townsend Deprivation Index at recruitment(OR:1.57;95%CI:1.04-2.37).These factors were found to independently and predominantly influence the genetic causal effect of GERD.Furthermore,the mediating effect of educational attainment on GERD was found to be mediated by MDD(proportion mediated:10.83%).Similarly,the effect of educational attainment on BE was mediated by MDD(proportion mediated:10.58%)and the number of cigarettes smoked per day(proportion mediated:3.50%).Additionally,the mediating effect of household income on GERD was observed to be mediated by sleep duration(proportion mediated:9.75%)CONCLUSION This MR study shed light on the link between socioeconomic status and GERD or BE,providing insights for the prevention of esophageal cancer and precancerous lesions.

Hybrid argon plasma coagulation for the treatment of Barrett’s esophagus:A prospective,multicenter study

BACKGROUND The incidence of Barrett’s esophagus(BE)in China is lower compared to the Western populations.Hence,studies conducted in the Chinese population has been limited.The current treatment options available for BE treatment includes argon plasma coagulation(APC),radiofrequency ablation and cryoablation,all with varying degrees of success.AIM To determine the efficacy and safety of HybridAPC in the treatment of BE.METHODS The study cohort consisted of patients with BE who underwent HybridAPC ablation treatment.These procedures were performed by seven endoscopists from different tertiary hospitals.The duration of the procedure,curative rate,complications and recurrent rate by 1-year follow-up were recorded.RESULTS Eighty individuals were enrolled for treatment from July 2017 to June 2020,comprising of 39 males and 41 females with a median age of 54 years(range,30 to 83 years).The technical success rate of HybridAPC was 100%and the overall curative rate was 98.15%.No severe complications occurred during the operation.BE cases were classified as short-segment BE and long-segment BE.Patients with short-segment BE were all considered cured without complications.Thirty-six patients completed the one-year follow-up without recurrence.Twenty-four percent had mild dysplasia which were all resolved with one post-procedural treatment.The mean duration of the procedure was 10.94±6.52 min.CONCLUSION Treatment of BE with HybridAPC was found to be a simple and quick procedure that is safe and effective during the short-term follow-up,especially in cases of short-segment BE.This technique could be considered as a feasible alternative ablation therapy for BE.

Gender disparities and woman-specific trends in Barrett’s esophagus in the United States:An 11-year nationwide populationbased study

BACKGROUND Barrett's esophagus(BE)is a known premalignant precursor to esophageal adenocarcinoma(EAC).The prevalence rates continue to rise in the United States,but many patients who are at risk of EAC are not screened.Current practice guidelines include male gender as a predisposing factor for BE and EAC.The population-based clinical evidence regarding female gender remains limited.AIM To study comparative trends of gender disparities in patients with BE in the United States.METHODS A nationwide retrospective study was conducted using the 2009-2019 National Inpatient Sample(NIS)database.Patients with a primary or secondary diagnosis code of BE were identified.The major outcome of interest was determining the gender disparities in patients with BE.Trend analysis for respective outcomes for females was also reported to ascertain any time-based shifts.RESULTS We identified 1204190 patients with BE for the study period.Among the included patients,717439(59.6%)were men and 486751(40.4%)were women.The mean age was higher in women than in men(67.1±0.4 vs 66.6±0.3 years,P<0.001).The rate of BE per 100000 total NIS hospitalizations for males increased from 144.6 in 2009 to 213.4 in 2019(P<0.001).The rate for females increased from 96.8 in 2009 to 148.7 in 2019(P<0.001).There was a higher frequency of obesity among women compared to men(17.4%vs 12.6%,P<0.001).Obesity prevalence among females increased from 12.3%in 2009 to 21.9%in 2019(P<0.001).A lower prevalence of smoking was noted in women than in men(20.8%vs 35.7%,P<0.001).However,trend analysis showed an increasing prevalence of smoking among women,from 12.9%in 2009 to 30.7%in 2019(P<0.001).Additionally,there was a lower prevalence of alcohol abuse,Helicobacter pylori(H.pylori),and diabetes mellitus among females than males(P<0.001).Trend analysis showed an increasing prevalence of alcohol use disorder and a decreasing prevalence of H.pylori and diabetes mellitus among women(P<0.001).CONCLUSION The prevalence of BE among women has steadily increased from 2009 to 2019.The existing knowledge concerning BE development has historically focused on men,but our findings show that the risk in women is not insignificant.

Short-segment Barrett's esophagus and cardia intestinal metaplasia:A comparative analysis

AIM:To investigate the endoscopy and histology of short-segment Barrett's esophagus (SSBE) and cardia intestinal metaplasia (CIM),and their correlation with Helicobacter pylori (H. pylori) gastritis and gastroesophageal reflux disease (GERD). METHODS:Biopsy specimens were taken from 32 SSBE patients and 41 CIM patients with normal appearance of the esophagogastric junction. Eight biopsy specimens from the lower esophagus,cardia,and gastric antrum were stained with hematoxylin/eosin,Alcian blue/periodic acid-Schiff,Alcian blue/high iron diamine and Gimenez dye. Results were graded independently by one pathologist. RESULTS:The SSBE patients were younger than the CIM patients (P < 0.01). The incidence of dysplasia and incomplete intestinal metaplasia subtype was higher in SSBE patients than in CIM patients (P < 0.01). H. pylori infection was correlated with antral intestinal metaplasia (P < 0.05),but not with reflux symptomatic,endoscopic,or histological markers of GERD in CIM patients. SSBE was correlated with reflux symptomatic and endoscopic esophagitis (P < 0.01),but not with H. pylori infection and antral intestinal metaplasia. CONCLUSION:Dysplasia risk is significantly greater in SSBE patients than in CIM patients. CIM is a manifestation of H. pylori-associated and multifocal atrophic gastritis,whereas SSBE may result from GERD.

Magnifying endoscopy for the diagnosis of specialized intestinal metaplasia in short-segment Barrett's esophagus

AIM:To determine whether magnified observation of short-segment Barrett’s esophagus(BE)is useful for the detection of specialized intestinal metaplasia(SIM).METHODS:Thirty patients with suspected short-segment BE underwent magnifying endoscopy up to×80.The magnified images were analyzed with respect to their pit-patterns,which were simultaneously classified into five epithelial types[Ⅰ(small round),Ⅱ(straight),Ⅲ(long oval),Ⅳ(tubular),Ⅴ(villous)]by Endo’s classification.Then,a 0.5%solution of methylene blue(MB)was sprayed over columnar mucosa.The patterns of the magnified image and MB staining were analyzed.Biopsies were obtained from the regions previously observed by magnifying endoscopy and MB chromoendoscopy.RESULTS:Three of five patients with a typeⅤ(villous)epithelial pattern had SIM,whereas 21 patients with a non-typeⅤepithelial patterns did not have SIM.The sensitivity,specificity,accuracy,positive predictive value,and negative predictive value of pit-patterns in detecting SIM were 100%,91.3%,92.3%,60%and100%,respectively(P=0.004).Three of the 12 patients with positive MB staining had SIM,whereas 14patients with negative MB staining did not have SIM.The sensitivity,specificity,accuracy,positive predictive value,and negative predictive value of MB staining in detecting SIM were 100%,60.9%,65.4%,25%and100%,respectively(P=0.085).The specificity and accuracy of pit-pattern evaluation were significantly superior compared with MB staining for detecting SIM by comparison with the exact McNemar’s test(P=0.0391).CONCLUSION:The magnified observation of a shortsegment BE according to the mucosal pattern and its classification can be predictive of SIM.

Artificial intelligence system for the detection of Barrett’s esophagus

BACKGROUND Barrett’s esophagus(BE),which has increased in prevalence worldwide,is a precursor for esophageal adenocarcinoma.Although there is a gap in the detection rates between endoscopic BE and histological BE in current research,we trained our artificial intelligence(AI)system with images of endoscopic BE and tested the system with images of histological BE.AIM To assess whether an AI system can aid in the detection of BE in our setting.METHODS Endoscopic narrow-band imaging(NBI)was collected from Chung Shan Medical University Hospital and Changhua Christian Hospital,resulting in 724 cases,with 86 patients having pathological results.Three senior endoscopists,who were instructing physicians of the Digestive Endoscopy Society of Taiwan,independently annotated the images in the development set to determine whether each image was classified as an endoscopic BE.The test set consisted of 160 endoscopic images of 86 cases with histological results.RESULTS Six pre-trained models were compared,and EfficientNetV2B2(accuracy[ACC]:0.8)was selected as the backbone architecture for further evaluation due to better ACC results.In the final test,the AI system correctly identified 66 of 70 cases of BE and 85 of 90 cases without BE,resulting in an ACC of 94.37%.CONCLUSION Our AI system,which was trained by NBI of endoscopic BE,can adequately predict endoscopic images of histological BE.The ACC,sensitivity,and specificity are 94.37%,94.29%,and 94.44%,respectively.

Graft dilatation and Barrett’s esophagus in adults after gastric pullup and jejunal interposition for long-gap esophageal atresia

BACKGROUND Esophageal replacement(ER)with gastric pull-up(GPU)or jejunal interposition(JI)used to be the standard treatment for long-gap esophageal atresia(LGEA).Changes of the ER grafts on a macro-and microscopic level however,are unknown.AIM To evaluate long-term clinical symptoms and anatomical and mucosal changes in adolescents and adults after ER for LGEA.METHODS A cohort study was conducted including all LGEA patients≥16 years who had undergone GPU or JI between 1985-2003 at two tertiary referral centers in the Netherlands.Patients underwent clinical assessment,contrast study and endoscopy with biopsy.Data was collected prospectively.Group differences between JI and GPU patients,and associations between different outcome measures were assessed using the Fisher’s exact test for bivariate variables and the Mann-Whitney U-test for continuous variables.Differences with a P-value<0.05 were considered statistically significant.RESULTS Nine GPU patients and eleven JI patients were included.Median age at follow-up was 21.5 years and 24.4 years,respectively.Reflux was reported in six GPU patients(67%)vs four JI patients(36%)(P=0.37).Dysphagia symptoms were reported in 64%of JI patients,compared to 22%of GPU patients(P=0.09).Contrast studies showed dilatation of the jejunal graft in six patients(55%)and graft lengthening in four of these six patients.Endoscopy revealed columnar-lined esophagus in three GPU patients(33%)and intestinal metaplasia was histologically confirmed in two patients(22%).No association was found between reflux symptoms and macroscopic anomalies or intestinal metaplasia.Three GPU patients(33%)experienced severe feeding problems vs none in the JI group.The median body mass index of JI patients was 20.9 kg/m^(2) vs 19.5 kg/m^(2) in GPU patients(P=0.08).CONCLUSION The majority of GPU patients had reflux and intestinal metaplasia in 22%.The majority of JI patients had dysphagia and a dilated graft.Follow-up after ER for LGEA is essential.

Role of artificial intelligence in Barrett’s esophagus

The application of artificial intelligence(AI)in gastrointestinal endoscopy has gained significant traction over the last decade.One of the more recent applications of AI in this field includes the detection of dysplasia and cancer in Barrett’s esophagus(BE).AI using deep learning methods has shown promise as an adjunct to the endoscopist in detecting dysplasia and cancer.Apart from visual detection and diagnosis,AI may also aid in reducing the considerable interobserver variability in identifying and distinguishing dysplasia on whole slide images from digitized BE histology slides.This review aims to provide a comprehensive summary of the key studies thus far as well as providing an insight into the future role of AI in Barrett’s esophagus.

MicroRNAs, development of Barrett’s esophagus, and progression to esophageal adenocarcinoma

Barrett's esophagus is a premalignant condition caused by gastroesophageal reflux. Once developed, it can progress through varying grades of dysplasia to esoph-ageal adenocarcinoma. Whilst it is well accepted that Barrett's esophagus is caused by gastroesophageal reflux, the molecular mechanisms of its pathogenesis and progression to cancer remain unclear. MicroRNAs (miRNAs) are short segments of RNA that have been shown to control the expression of many human genes. They have been implicated in most cellular processes, and the role of miRNAs in disease development is be-coming increasingly evident. Understanding altered miRNA expression is likely to help unravel the molecular mechanisms that underpin the development of Barrett's esophagus and its progression to cancer.

Cdx2 expression and its promoter methylation during metaplasia-dysplasia-carcinoma sequence in Barrett's esophagus

AIM:To examine how the expression of caudal type homebox transcription factor 2(Cdx2) is regulated in the development of malignancy in Barrett's esophagus.METHODS:Cdx2,mucin(MUC) series(MUC2,MUC5AC and MUC6),p53 and E-cadherin expression in Barrett's esophagus and adenocarcinoma specimens were examined by immunostaining.Isolated clusters of cells from(1) MUC2 and Cdx2-positive intestinal metaplastic mucosa;(2) MUC5AC and MUC6-positive,and MUC2 and Cdx2-negative high-grade dysplasia(HD),or intramucosal adenocarcinoma(IMC);and(3) MUC5AC,MUC6 and Cdx2-positive poorly-differentiated invasive adenocarcinoma(PDA) were analyzed by methylationspecific polymerase chain reaction using sets of primers for detecting methylation status of the Cdx2 gene.RESULTS:Most of the non-neoplastic Barrett's esophageal mucosa showing intestinal-type metaplasia with or without low-grade dysplasia was positive for E-cadherin,MUC series and Cdx2,but negative for p53.A portion of the low-grade to HD was positive for E-cadherin,MUC5AC,MUC6 and p53,but negative for MUC2 and Cdx2.The definite IMC area was strongly positive for MUC5AC,MUC6 and p53,but negative for MUC2 and Cdx2.Methylation of the Cdx2 promoter was not observed in intestinal metaplasia,while hypermethylation of part of its promoter was observed in hot dipped and IMC.Hypermethylation of a large fraction of the Cdx2 promoter was observed in PDA.CONCLUSION:Cdx2 expression is restored irrespective of the methylation status of its promoter.Apparent positive immunohistochemical results can be a molecular mark for gene silencing memory.

miR-200 family expression is downregulated upon neoplastic progression of Barrett's esophagus

AIM: To investigate miR-200 family expression in Barrett's epithelium, gastric and duodenal epithelia, and esophageal adenocarcinoma. METHODS: Real-time reverse transcriptase-polymerase chain reaction was used to measure miR-200, ZEB1 and ZEB2 expression. Ingenuity Pathway Analysis of miR-200 targets was used to predict biological outcomes. RESULTS: Barrett's epithelium expressed lower levels of miR-141 and miR-200c than did gastric and duodenal epithelia (P < 0.001). In silico analysis indicated roles for the miR-200 family in molecular pathways that distinguish Barrett's epithelium from gastric and duodenalepithelia, and which control apoptosis and proliferation. All miR-200 members were downregulated in adenocarcinoma (P < 0.02), and miR-200c expression was also downregulated in non-invasive epithelium adjacent to adenocarcinoma (P < 0.02). The expression of all miR-200 members was lower in Barrett's epithelium derived high-grade dysplastic cell lines than in a cell line derived from benign Barrett's epithelium. We observed signif icant inverse correlations between miR-200 family expression and ZEB1 and ZEB2 expression in Barrett's epithelium and esophageal adenocarcinoma (P < 0.05). CONCLUSION: miR-200 expression might contribute to the anti-apoptotic and proliferative phenotype of Barrett's epithelium and regulate key neoplastic processes in this epithelium.

Biomarkers in Barrett's esophagus and esophageal adenocarcinoma:Predictors of progression and prognosis

Barrett’s esophagus is a well-known premalignant lesion of the lower esophagus that is characterized by intestinal metaplasia of the squamous epithelium. It is clinically important due to the increased risk (0.5% per annum) of progression to esophageal adenocarcinoma (EA), which has a poor outcome unless diagnosed early. The current clinical management of Barrett’s esophagus is hampered by the lack of accurate predictors of progression. In addition, when patients develop EA, the current staging modalities are limited in stratifying patients into different prognostic groups in order to guide the optimal therapy for an individual patient. Biomarkers have the potential to improve radically the clinical management of patients with Barrett’s esophagus and EA but have not yet entered mainstream clinical practice. This is in contrast to other cancers like breast and prostate for which biomarkers are utilized routinely to inform clinical decisions. This review aims to highlight the most promising predictive and prognostic biomarkers in Barrett’s esophagus and EA and to discuss what is required to move the field forward towards clinical application.

Cyclooxygenase-2 and epithelial growth factor receptor up-regulation during progression of Barrett's esophagus to adenocarcinoma

AIM： To investigate the expression of cyclooxygenase-2 （COX-2） and epithelial growth factor receptor （EGFR） throughout the progression of Barrett＇s esophagus （BE）. METHODS： COX-2 and EGFR protein expressions were detected by using immunohistochemical method. A detailed cytomorphological changes were determined. Areas of COX-2 and EGFR expression were quantified by using computer Imaging System. RESULTS： The expressions of both COX-2 and EGFR increased along with the progression from BE to esophagus adenocarcinoma （EAC）. A positive correlation was found between COX-2 expression and EGFR expression. CONCLUSION： COX-2 and EGFR may be cooperative in the stepwise progression from BE to EAC, thereby leading to carcinogenesis.

Low circulating levels of gastrin-17 in patients with Barrett's esophagus

AIM: To examine whether the fasting levels of serum gastrin-17 (G-17) are lower in Barrett's esophagus (BE)patients than in non-Barrett controls.METHODS: Nineteen patients with BE (presenting with a tubular segment ≥2 cm long in lower esophagus and intestinal metaplasia of incomplete type ('specialized columnar epithelium') in endoscopic biopsies from the tubular segment below the squamocolumnar junction were collected prospectively from outpatients referred to diagnostic gastroscopy. The controls comprised 199 prospectively collected dyspeptic outpatients without BE or any endoscopically visible lesions in the upper GI tract.Fasting levels of serum G-17 (G-17fast) were assayed with an EIA test using a Mab highly specific to amidated G-17. None of the patients and controls received therapy with PPIs or other antisecretory agents.RESULTS: The mean and median levels of G-17fast in serum were significantly lower (P = 0.001) in BE patients than in controls. The positive likelihood ratios (LR+) of low G-17fast to predict BE in the whole study population at G-17fast levels ＜0.5, ＜1, or ＜1.5 pmol/L were 3.5, 3.0,and 2.8, respectively. Among patients and controls with healthy stomach mucosa, the LR+ were 5.6, 3.8, and 2.6,respectively. In the whole study population, serum G-17 was below 2 pmol/L in 15 of 19 BE patients (79%). The corresponding prevalence was 66 of 199 (33%) in controls (P＜0.001). The G-17fast was 5 pmol/L or more in only one of the 19 BE patients (5%). In controls, 76 of the 199 patients (38%) had such high serum G-17fast levels (P＜0.01).CONCLUSION: Serum levels of G-17fast tend to be lower in native patients with BE than in healthy controls.

Role of interleukin-6 in Barrett's esophagus pathogenesis

Barrett's esophagus (BE) is a metaplastic lesion of the distal esophagus arising as a consequence of chronic gastroesophageal reflux disease. Multiple studies show that BE is associated with increased risk of esophageal adenocarcinoma (EAC). Epidemiological studies and animal models demonstrate that chronic inflammation triggered by repeated exposure to refluxate predisposes to the development of BE and EAC. The chronic inflammation is associated with cytokine alterations. Interleukin 6 (IL-6) is a cytokine that stimulates cell proliferation and apoptosis resistance is frequently increased in different cancers. Importantly, IL-6 and transcriptional factor signal transducer and activator of transcription 3 (STAT3) that is activated by IL-6 are also increased in BE and EAC. This review critically appraises the role of IL-6/STAT3 pathway in progression of BE to EAC from the published evidence currently available.

Risk factors for neoplastic progression in Barrett's esophagus

Barrett's esophagus (BE) confers a significant increased risk for development of esophageal adenocarcinoma (EAC), with the pathogenesis appearing to progress through a "metaplasia-dysplasia-carcinoma" (MDC) sequence. Many of the genetic insults driving this MDC sequence have recently been characterized, providing targets for candidate biomarkers with potential clinical utility to stratify risk in individual patients. Many clinical risk factors have been investigated, and associations with a variety of genetic, specific gastrointestinal and other modifiable factors have been proposed in the literature. This review summarizes the current understanding of the mechanisms involved in neoplastic progression of BE to EAC and critically appraises the relative roles and contributions of these putative risk factors from the published evidence currently available.

Prevalence and risk factors for Barrett’s esophagus in Taiwan

BACKGROUND Barrett’s esophagus(BE)is a pre-malignant condition associated with the development of esophageal adenocarcinoma.The prevalence of BE in the general populations of Asian countries ranges from 0.06%to 1%.However,with lifestyle changes in Asian countries and adoption of western customs,the prevalence of BE might have increased.AIM To determine the current prevalence of BE in Taiwan,and to investigate risk factors predicting the presence of BE.METHODS This retrospective study was conducted at the Health Evaluation Center of Kaohsiung Veterans General Hospital in Taiwan.Between January 2015 and December 2015,3385 subjects undergoing routine esophagogastroduodenoscopy examinations as part of a health check-up at the Health Evaluation Center were included.Patient characteristics and endoscopic findings were carefully reviewed.Lesions with endoscopic findings consistent with BE awaiting histological evaluation were judged as endoscopically suspected esophageal metaplasia(ESEM).BE was defined based on extension of the columnar epithelium≥1 cm above the gastroesophageal junction and was confirmed based on the presence of specialized intestinal metaplasia(IM)in the metaplastic esophageal epithelium.Clinical factors of subjects with BE and subjects without BE were compared,and the risk factors predicting BE were analyzed.RESULTS A total of 3385 subjects(mean age,51.29±11.42 years;57.1%male)were included in the study,and 89 among them were confirmed to have IM and presence of goblet cells via biopsy examination.The majority of these individuals were classified as short segment BE(n=85).The overall prevalence of BE was 2.6%.Multivariate analysis disclosed that old age[odds ratio(OR)=1.033;95%confidence interval(CI):1.012-1.055;P=0.002],male gender(OR=2.106;95%CI:1.145-3.872;P=0.017),ingestion of tea(OR=1.695;95%CI:1.043-2.754;P=0.033),and presence of hiatal hernia(OR=3.037;95%CI:1.765-5.225;P<0.001)were significant risk factors predicting BE.The independent risk factor for the presence of IM in ESEM lesions was old age alone(OR=1.029;95%CI:1.006-1.053;P=0.014).CONCLUSION Current prevalence of BE among the general population in Taiwan is 2.6%.Old age,male gender,ingestion of tea and hiatal hernia are significant risk factors for BE.

Biomarker identification and trans-regulatory network analyses in esophageal adenocarcinoma and Barrett's esophagus

BACKGROUND Esophageal adenocarcinoma(EAC) is an aggressive disease with high mortality and an overall 5-year survival rate of less than 20%. Barrett's esophagus(BE) is the only known precursor of EAC, and patients with BE have a persistent and excessive risk of EAC over time. Individuals with BE are up to 30-125 times more likely to develop EAC than the general population. Thus, early detection of EAC and BE could significantly improve the 5-year survival rate of EAC. Due to the limitations of endoscopic surveillance and the lack of clinical risk stratification strategies, molecular biomarkers should be considered and thoroughly investigated.AIM To explore the transcriptome changes in the progression from normal esophagus(NE) to BE and EAC.METHODS Two datasets from the Gene Expression Omnibus(GEO) in NCBI Database(https://www.ncbi.nlm.nih.gov/geo/) were retrieved and used as a training and a test dataset separately, since NE, BE, and EAC samples were included and the sample sizes were adequate. This study identified differentially expressed genes(DEGs) using the R/Bioconductor project and constructed trans-regulatory networks based on the Transcriptional Regulatory Element Database and Cytoscape software. Enrichment of Kyoto Encyclopedia of Genes and Genomes(KEGG) and Gene Ontology(GO) terms was identified using the Database for Annotation, Visualization, and Integrated Discovery(DAVID) Bioinformatics Resources. The diagnostic potential of certain DEGs was assessed in both datasets.RESULTS In the GSE1420 dataset, the number of up-regulated DEGs was larger than that of down-regulated DEGs when comparing EAC vs NE and BE vs NE. Among these DEGs, five differentially expressed transcription factors(DETFs) displayed the same trend in expression across all the comparison groups. Of these five DETFs,E2 F3, FOXA2, and HOXB7 were up-regulated, while PAX9 and TFAP2 C were down-regulated. Additionally, the majority of the DEGs in trans-regulatory networks were up-regulated. The intersection of these potential DEGs displayed the same direction of changes in expression when comparing the DEGs in the GSE26886 dataset to the DEGs in trans-regulatory networks above. The receiver operating characteristic curve analysis was performed for both datasets and found that TIMP1 and COL1 A1 could discriminate EAC from NE tissue, while REG1 A, MMP1, and CA2 could distinguish BE from NE tissue. DAVID annotation indicated that COL1 A1 and MMP1 could be potent biomarkers for EAC and BE, respectively, since they participate in the majority of the enriched KEGG and GO terms that are important for inflammation and cancer.CONCLUSION After the construction and analyses of the trans-regulatory networks in EAC and BE, the results indicate that COL1 A1 and MMP1 could be potential biomarkers for EAC and BE, respectively.

Superoxide dismutase prevents development of adenocarcinoma in a rat model of Barrett's esophagus

AIM： To test whether antioxidant treatment could prevent the progression of Barrett＇s esophagus to adenocarcinoma. METHODS： In a rat model of gastroduodenoesophageal reflux by esophagojejunal anastomosis with gastric preservation, groups of 6-10 rats were randomized to receive treatment with superoxide dismutase （SOD） or vehicle and followed up for 4 too. Rat＇s esophagus was assessed by histological analysis, superoxide anion and peroxinitrite generation, SOD levels and DNA oxidative damage. RESULTS： All rats undergoing esophagojejunostomy developed extensive esophageal mucosal ulceration and inflammation by mo 4. The process was associated with a progressive presence of intestinal metaplasia beyond the anastomotic area （9% 1st mo and 50% 4th too） （94% at the anastomotic level） and adenocarcinoma （11% 1^ST mo and 60% 4th too）. These changes were associated with superoxide anion and peroxinitrite mucosal generation, an early and significant increase of DNA oxidative damage and a significant decrease in SOD levels （P〈0.05）. Exogenous administration of SOD decreased mucosal superoxide levels, increased mucosal SOD levels and reduced the risk of developing intestinal metaplasia beyond the anastomotic area （odds ratio = 0.326; 95%CI： 0.108-0.981; P = 0.046）, and esophageal adenocarcinoma （odds ratio = 0.243; 95%CI： 0.073-0.804; P = 0.021）. CONCLUSION： Superoxide dismutase prevents the progression of esophagitis to Barrett＇s esophagus and adenocarcinoma in this rat model of gastrointestinal reflux, supporting a role of antioxidants in the chemoprevention of esophageal adenocarcinoma.

Barrett's esophagus:Prevalence and risk factors in patients with chronic GERD in Upper Egypt

AIM： To determine the prevalence and possible risk factors of Barrett＇s esophagus （BE） in patients with chronic gastroesophageal reflux disease （GERD） in EI Minya and Assuit, Upper Egypt. METHODS： One thousand consecutive patients with chronic GERD symptoms were included in the study over 2 years. They were subjected to history taking including a questionnaire for GERD symptoms, clinical examination and upper digestive tract endoscopy. Endoscopic signs suggestive of columnar-lined esophagus （CLE） were defined as mucosal tongues or an upward shift of the squamocolumnar junction. BF was diagnosed by pathological examination when specialized intestinal metaplasia was detected histologically in suspected CLE. pH was monitored in 40 patients. RESULTS： BE was present in 7.3% of patients with chronic GERD symptoms, with a mean age of 48.3 ± 8.2 years, which was significantly higher than patients with GERD without BE （37.4 ± 13.6 years）. Adenocarcinoma was detected in eight cases （0.8%）, six of them in BE patients. There was no significant difference between patients with BE and GERD regarding sex, smoking, alcohol consumption or symptoms of GERD. Patients with BE had significantly longer esophageal acid exposure time in the supine position, measured by pH monitoring. CONCLUSION： The prevalence of BE in patients with GERD who were referred for endoscopy was 7.3%. BE seems to be associated with older age and more in patients with nocturnal gastroesophageal reflux.