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.

Is Helicobacter pylori infection protective against esophageal cancer?

Helicobacter pylori(H.pylori)infection affects a substantial proportion of the global population and causes various gastric disorders,including gastric cancer.Recent studies have found an inverse relationship between H.pylori infection and eso-phageal cancer(EC),suggesting a protective role against EC.This editorial focuses on the possible mechanisms underlying the role of H.pylori infection in EC and explores the role of gut microbiota in esophageal carcinogenesis and the prac-ticality of H.pylori eradication.EC has two major subtypes:Esophageal squamous cell carcinoma(ESCC)and esophageal adenocarcinoma(EAC),which have different etiologies and risk factors.Gut microbiota can contribute to EC via inflammation-induced carcinogenesis,immunomodulation,lactagenesis,and genotoxin production.H.pylori infection is said to be inversely related to EAC,protecting against EAC by inducing atrophic gastritis,altering serum ghrelin levels,and triggering cancer cell apoptosis.Though H.pylori infection has no significant association with ESCC,COX-2-1195 polymorphisms and endogenous nitrosamine production can impact the risk of ESCC in H.pylori-infected in-dividuals.There are concerns regarding a plausible increase in EC after H.pylori eradication treatments.However,H.pylori eradication is not associated with an increased risk of EC,making it safe from an EC perspective.

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.

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.

Exercise benefits meet the esophagus

Gastroesophageal reflux disease(GERD)is defined by recurrent and troublesome heartburn and effortless regurgitation or by the specific complications of this condition—that is,esophagitis,esophageal peptic strictures,and Barrett esophagus.1Although GERD is caused by gastric contents'reaching the esophagus,gastric juices can also reach other anatomical locations(pharynx,mouth,larynx,and airways),leading to(or worsening)extra-esophageal conditions(notably asthma)or symptoms(e.g.,wheezing,cough).1 Together with obesity,GERD is the main risk factor for gastroesophageal malignancies.

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.

Total removal of a large esophageal schwannoma by submucosal tunneling endoscopic resection:A case report and review of literature

BACKGROUND Primary schwannoma is a rare submucosal tumor of the esophagus,which is most often benign,and surgery is the only effective treatment.So far,only a few cases have been reported.Herein,we reported a single case diagnosed with primary esophageal schwannoma that was totally removed by submucosal tunneling endoscopic resection(STER).CASE SUMMARY A 62-year-old man presented to the hospital with a history of resection of a malignant gastric tumor and mild dysphagia.Endoscopic examination revealed a large submucosal elevated lesion in the esophagus 25-30 cm from the incisors.Endoscopic ultrasonography detected a 45 mm×35 mm×31 mm hypoechoic lesion;chest computed tomography showed a mass of approximately 55 mm×35 mm×29 mm.A preliminary examination showed features suggestive of a stromal tumor.Pathological findings indicated esophageal schwannoma.Next,STER alone was performed to completely resect the mass,and the patient recovered well post-surgery.Afterward,the patient was discharged and showed no tumor recurrence at 33 mo of follow-up.CONCLUSION Endoscopic resection is still an effective treatment for large esophageal schwannomas(>30 mm)under meticulous morphological evaluation.

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.

Confocal Laser Endomicroscopy in the Field of Esophageal Diseases

Confocal laser endomicroscopy (CLE) is a new endoscopic imaging technology that allows real-time, high-resolution observation of tomographic images of mucosal cells and subcellular levels in vivo, detecting microscopic structural changes in mucosal morphology, and its in vivo immediate pathological diagnostic capability can avoid delays in mucosal pathological diagnosis and reduce the pain caused by repeated biopsies. CLE is known as “optical biopsy” and compared with other endoscopic techniques, it has obvious advantages. CLE systems include probe-based confocal laser endomicroscopy (pCLE) and endoscope-based confocal laser endomicroscopy (eCLE). Since 2006, CLE has been widely used for the evaluation of various lesions in the digestive system, including esophageal, gastric, and colonic neoplasia, pancreatic cysts and solid lesions, and inflammatory bowel disease. The advent of CLE has made in vivo microscopic imaging possible, which has changed the endoscopic screening and diagnosis of multiple gastrointestinal (GI) lesions. However, the value of its use in GI diseases is still controversial. In this review, we focus on the application of CLE in the field of esophageal diseases.

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.

Molecular biology of Barrett's esophagus and esophageal cancer:role of p53

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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.

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.

Alteration of the esophageal microbiota in Barrett's esophagus and esophageal adenocarcinoma

The incidence of esophageal adenocarcinoma(EAC) has increased in recent decades, and its 5-year survival rate is less than 20%. As a well-established precursor, patients with Barrett's esophagus(BE) have a persistent risk of progression to EAC. Many researchers have already identified some factors that may contribute to the development of BE and EAC, and the identified risks include gastroesophageal reflux(GER), male sex, older age, central obesity,tobacco smoking, Helicobacter pylori(H. pylori) eradication, and the administration of proton pump inhibitors(PPIs) and antibiotics. The human gut harbors trillions of microorganisms, the majority of which are bacteria. These microorganisms benefit the human host in many ways, such as helping in digestion, assisting in the synthesis of certain vitamins, promoting the development of the gastrointestinal immune system, regulating metabolism and preventing invasion by specific pathogens. In contrast, microbial dysbiosis may play important roles in various diseases, such as inflammation and cancers. The composition of the microbiota located in the normal esophagus is relatively conserved without distinct microbial preferences in the upper, middle and lower esophagus. Six major phyla constitute the esophageal microbiota, including Firmicutes,Bacteroides, Actinobacteria, Proteobacteria, Fusobacteria and TM7, similar to the oral microbiota. Streptococcus dominates the esophageal microbiota. However, the microbiota varies in different esophageal diseases compared to that in the healthy esophagus. The type Ⅰ microbiota, which is primarily composed of gram-positive bacteria, is closely associated with the normal esophagus, while type Ⅱ microbiota has enriched gram-negative bacteria and is mainly associated with the abnormal esophagus. These increased gram-negative anaerobes/microaerophiles include Veillonella, Prevotella, Haemophilus, Neisseria, Granulicatella and Fusobacterium, many of which are associated with BE. The microbial diversity in the esophagus is decreased in EAC patients, and Lactobacillus fermentum is enriched compared to that in controls and BE patients. Furthermore, the microbiota may be associated with BE and EAC by interacting with their risk factors, including central obesity, GER, H. pylori, administration of PPIs and antibiotics. Therefore, a large gap in research must be bridged to elucidate the associations among these factors. Some studies have already proposed several potential mechanisms by which the microbiota participates in human carcinogenesis by complicated interactions with the human host immune system and signaling pathways. The activation of the LPS-TLR4-NF-κB pathway may contribute to inflammation and malignant transformation. This exciting field of gastrointestinal microbiota allows us to unravel the mystery of carcinogenesis from another perspective. Further studies are needed to explore whether the microbiota changes before or after disease onset, to improve our understanding of the pathogenesis, and to find novel targets for prevention, diagnosis and therapy, which could offer more cost-effective and relatively safe choices.

From reflux esophagitis to Barrett's esophagus and esophageal adenocarcinoma

The occurrence of gastroesophageal reflux disease is common in the human population.Almost all cases of esophageal adenocarcinoma are derived from Barrett's esophagus,which is a complication of esophageal adenocarcinoma precancerous lesions.Chronic exposure of the esophagus to gastroduodenal intestinal fluid is an important determinant factor in the development of Barrett's esophagus.The replacement of normal squamous epithelium with specific columnar epithelium in the lower esophagus induced by the chronic exposure to gastroduodenal fluid could lead to intestinal metaplasia,which is closely associated with the development of esophageal adenocarcinoma.However,the exact mechanism of injury is not completely understood.Various animal models of the developmental mechanisms of disease,and theoretical and clinical effects of drug treatment have been widely used in research.Recently,animal models employed in studies on gastroesophageal reflux injury have allowed significant progress.The advantage of using animal models lies in the ability to accurately control the experimental conditions for better evaluation of results.In this article,various modeling methods are reviewed,with discussion of the major findings on the developmental mechanism of Barrett's esophagus,which should help to develop better prevention and treatment strategies for Barrett's esophagus.

Barrett's esophagus with high grade dysplasia is associated with non-esophageal cancer

AIM To study factors associated with esophageal and nonesophageal cancer morbidity among Barrett's esophagus(BE) patients. METHODS A cohort study within a single tertiary center included 386 consecutive patients with biopsy proven BE, who were recruited between 2004-2014. Endoscopic and histologic data were prospectively recorded. Cancer morbidity was obtained from the national cancer registry. Main outcomes were BE related(defined as esophagus and cardia) and non-BE related cancers(all other cancers). Cancer incidence and all-causemortality were compared between patients with highgrade dysplasia(HGD) and with low-grade or no dysplasia(non-HGD) using Kaplan-Meier curves and cox regression models.RESULTS Of the 386 patients, 12 had HGD, 7 had a BE related cancer. There were 75(19.4%) patients with 86 cases of lifetime cancers, 76 of these cases were non-BE cancers. Seven(1.8%) and 18(4.7%) patients had BE and non-BE incident cancers, respectively. Twelve(3.1%) patients had HGD as worst histologic result. Two(16.7%) and 16(4.4%) incident non-BE cancers occurred in the HGD and non-HGD group, respectively. Ten-year any cancer and non-BE cancer free survival was 63% and 82% in the HGD group compared to 93% and 95% at the non-HGD group, respectively. Log-rank test for patients with more than one endoscopy, assuring longer follow up, showed a significant difference(P < 0.001 and P = 0.017 respectively). All-cause mortality was not significantly associated with BE HGD.CONCLUSION Patients with BE and HGD, may have a higher risk for all-cause cancer morbidity. The implications on cancer prevention recommendations should be further studied.

Distinction between short-segment Barrett's esophageal and cardiac intestinal metaplasia

AIM： To investigate the roles of mucin histochemistry, cytokeratin 7/20 （CK7/20） immunoreactivity, clinical characteristics and endoscopy to distinguish short- segment Barrett＇s esophageal （SSBE） from cardiac intestinal metaplasia （CIM）. METHODS： High iron diamine/Alcian blue （HID/AB） mucin-histochemical staining and immunohistochemical staining were used to classify intestinal metaplasia （IN） and to determine CK7/20 immunoreactivity pattern in SSBE and CIM, respectively, and these results were compared with endoscopical diagnosis and the positive rate of gastroesophageal reflux disease （GERD） symptoms and H pylori infection. Long-segment Barrett＇ s esophageal and IM of gastric antrum were designed as control. RESULTS： The prevalence of type III IM was significantly higher in SSBE than in CIM （63.33% vs 23.08%, P〈0.005）. The CK7/20 immunoreactivity in SSBE showed mainly Barrett＇s pattern （76.66%）, and the GERD symptoms in most cases which showed Barrett＇ s pattern were positive, whereas H pylori infection was negative. However, the CK7/20 immunoreactivity in CIM was gastric pattern preponderantly （61.54%）, but there were 23.08% cases that showed Barrett＇s pattern. H pylori infection in all cases which showed gastric pattern was significantly higher than those which showed Barrett＇ s pattern （63.83% vs 19.30%, P〈0.005）, whereas the GERD symptoms in gastric pattern were significantly lower than that in Barrett＇s pattern （21.28% vs 85.96%,P〈O.O05）. CONCLUSION： Distinction of SSBE from CIM should not be based on a single method; however, the combination of clinical characteristics, histology, mucin histochemistry, CK7/20 immunoreactivity, and endoscopic biopsy should be applied. Type III IM, presence of GERD symptoms, and Barrett＇s CK7/20 immunoreactivity pattern may support the diagnosis of SSBE, whereas non-type III IM, positive H pylori infection, and gastric CK7/20 immunoreactivity pattern may imply CIM.

Risk factors for Barrett’s oesophagus and oesophageal adenocarcinoma:Results from the FINBAR study

AIM:To investigate risk factors associated with Barrett's oesophagus and oesophageal adenocarcinoma.METHODS:This all-Ireland population-based case-control study recruited 224 Barrett's oesophagus patients,227 oesophageal adenocarcinoma patients and 260 controls.All participants underwent a structured interview with information obtained about potential lifestyle and environmental risk factors.RESULTS:Gastro-oesophageal reflux was associated with Barrett's [OR 12.0(95% CI 7.64-18.7)] and oesophageal adenocarcinoma [OR 3.48(95% CI 2.25-5.41)].Oesophageal adenocarcinoma patients were more likely than controls to be ex-or current smokers [OR 1.72(95% CI 1.06-2.81)and OR 4.84(95% CI 2.72-8.61)respectively] and to have a high body mass index [OR 2.69(95% CI 1.62-4.46)].No significant associations were observed between these risk factors and Barrett's oesophagus.Fruit but not vegetables were negatively associated with oesophageal adenocarcinoma [OR 0.50(95% CI 0.30-0.86)].CONCLUSION:A high body mass index,a diet low in fruit and cigarette smoking may be involved in the progression from Barrett's oesophagus to oesophageal adenocarcinoma.

Psychosocial factors and their association with reflux oesophagitis,Barrett's oesophagus and oesophageal adenocarcinoma

AIM:To investigate the role of psychological characteristics as risk factors for oesophageal adenocarcinoma(OAC),as well as the reflux-mediated precursor pathway.METHODS:An all-Ireland population-based case-control study recruited 230 reflux oesophagitis(RO),224 Barrett's oesophagus(BO) and 227 OAC patients and 260 controls.Each case/control group completed measures of stress,depression,self-efficacy,self-esteem,repression and social support.A comparative analysis was undertaken using polytomous logistic regression adjusted for potential confounders.RESULTS:Compared to controls,OAC patients were almost half as likely to report high stress levels over their lifetime(P = 0.010,OR 0.51;95%CI:0.29-0.90)and 36% less likely to report having experienced depression(OR 0.64;95%CI:0.42-0.98).RO patients reported significantly higher stress than controls particularly during middle-and senior-years(P for trends < 0.001).RO patients were 37% less likely to report having been highly emotionally repressed(OR 0.63;95%CI:0.41-0.95).All case groups(OAC,RO and BO) were more likely than controls to report having had substantial amounts of social support(OR 2.84;95%CI:1.63-4.97;OR 1.97;95%CI:1.13-3.44 and OR 1.83;95%CI:1.03-3.24,respectively).CONCLUSION:The improved psychological profile of OAC patients may be explained by response shift.The role of psychological factors in the development of OAC requires further investigation.

Gene expression in rats with Barrett's esophagus and esophageal adenocarcinoma induced by gastroduodenoesophageal reflux

AIM: To study the different gene expression profiles in rats with Barrett's esophagus (BE) and esophageal adenocarcinoma (EA) induced by gastro-duodenoesophageal reflux.METHODS: Esophagoduodenostomy was performed in 8-wk old Sprague-Dawley rats to induce gastro-duodenoesophageal reflux, and a group of rats that received sham operation served as control. Esophageal epithelial pathological tissues were dissected and frozen in liquid nitrogen immediately. The expression profiles of 4 096genes in EA and BE tissues were compared to normal esophagus epithelium in normal control (NC) by cDNA microarray.RESULTS: Four hundred and forty-eight genes in BE were more than three times different from those in NC, including 312 upregulated and 136 downregulated genes. Three hundred and seventy-seven genes in EA were more than three times different from those in NC, including 255upregulated and 142 downregulated genes. Compared to BE, there were 122 upregulated and 156 downregulated genes in EA. In the present study, the interested genes were those involved in carcinogenesis. Among them, the upregulated genes included cathepsin C, aminopeptidase M, arachidonic acid epoxygenase, tryptophan-2,3-dioxygenase, ubiquitin-conjugating enzyme, cyclic GMP-stimulated phosphodiesterase, tissue inhibitor of metalloproteinase-1, betaine-homocysteine methyltransferase, lysozyme, complement 4b binding protein,complement 9 protein, insulin-like growth factor binding protein, UDP-glucuronosyltransferase, tissue inhibitor of metalloproteinase-3, aldolase B, retinoid X receptor gamma, carboxylesterase and testicular cell adhesion molecule 1. The downregulated genes included glutathione synthetase, lecithin-cholesterol acyltransferase, p55CDC,heart fatty acid binding protein, cell adhesion regulator and endothelial cell selectin ligand.CONCLUSION: Esophageal epithelium exposed excessively to harmful ingredients of duodenal and gastric reflux may develop into BE and even EA gradually. The gene expression level is different between EA and BE, and may be related to the occurrence and progression of EA.