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 li...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.展开更多
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 ...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.展开更多
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,...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.展开更多
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 ...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.展开更多
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 lev...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.展开更多
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 dyspla...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.展开更多
Objective:To investigate the efficacy and safety of the second generation argon plasma coagulation(VIO APC) in the ablation of Barrett' s Esophagus. Methods:A total of 35 patients with uncomplicated Barrett' s e...Objective:To investigate the efficacy and safety of the second generation argon plasma coagulation(VIO APC) in the ablation of Barrett' s Esophagus. Methods:A total of 35 patients with uncomplicated Barrett' s esophagus entered into a prospective, randomized, unblinded study comparing the treatment VIO APC combined with a proton pump inhibiter with a proton pump inhibiter administered alone. VIO APC was performed at a power setting of 40W, and argon gas flow at 1.5-2.0 L/min, and" forced" mode. Ablative treatment was repeated until either no Barrett' s epithelium remained or a maximum of 5 treatment sessions occurred. Results:In the ablation group, macroscopic complete ablation was achieved in 14 of 18 patients, and complete ablation confirmed by histology in 12 of 18 patients (P 〈 0.01). Buried glands were observed in 2 patients who had achieved macroscopic ablation. The Barrett's mucosa averaged a reduction of 65%(range 50-75%) in the remaining 4 patients. In the control group, only 2 patients had partial regression, median 30%(range 20-40%). In the ablation group, post-treatment 4 patients had transient retrosternal pain, and 3 patients had mild epigastric discomfort. One patient had a small hemorrhage during the procedure, which ceased after norepinephrine and thrombosin were administered through the endoscope biopsy channel. No adverse events were observed in the control group. During 11.8(4-15) months follow-up, patients who had achieved the complete ablation have no evidence of relapse of Barrett' s esophagus. Conclusion:VIO APC with a relatively low power setting can effectively ablate the Barrett' s mucosa. No severe adverse events were observed. Long-term follow-up is needed to assess cancer prevention and the durability of the neo-squamous epithelium.展开更多
The rising incidence of esophageal adenocarcinoma(EAC) in the world has led to continued interest in its precursor lesion, Barrett' s esophagus(BE). This review endeavors to summarize the recent advances in the t...The rising incidence of esophageal adenocarcinoma(EAC) in the world has led to continued interest in its precursor lesion, Barrett' s esophagus(BE). This review endeavors to summarize the recent advances in the therapy of BE with an emphasis on novel endoscopic therapies.展开更多
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 ...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.展开更多
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 segme...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.展开更多
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 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.展开更多
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 gastr...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.展开更多
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 ...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.展开更多
The natural history of Barrett's esophagus (BE) is difficult to quantify because,by definition,it should describe the course of the condition if left untreated.Pragmatically,we assume that patients with BE will re...The natural history of Barrett's esophagus (BE) is difficult to quantify because,by definition,it should describe the course of the condition if left untreated.Pragmatically,we assume that patients with BE will receive symptomatic treatment with acid suppression,usually a proton pump inhibitor,to treat their heartburn.This paper describes the development of complications of stricture,ulcer,dysplasia and adenocarcinoma from this standpoint.Controversies over the definition of BE and its implications in clinical practice are presented.The presence of intestinal metaplasia and its relevance to cancer risk is discussed,and the need to measure the extent of the Barrett's epithelium (long and short segments) using the Prague guidelines is emphasized.Guidelines and international consensus over the diagnosis and management of BE are being regularly updated.The need for expert consensus is important due to the lack of randomized trials in this area.After searching the literature,we have tried to collate the important studies regarding progression of Barrett's to dysplasia and adenocarcinoma.No therapeutic studies yet reported show a clear reduction in the development of cancer in BE.The effect of pharmacological and surgical intervention on the natural history of Barrett's is a subject of ongoing research,including the Barrett's Oesophagus Surveillance Study and the aspirin and esomeprazole cancer chemoprevention trial with interesting results.The geographical variation and the wide range of outcomes highlight the difficulty of providing an individualized risk profile to patients with BE.Future studies on the interaction of genome wide abnormalities in Barrett's and their interaction with environmental factors may allow individualization of the risk of cancer developing in BE.展开更多
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...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.展开更多
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 a...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.展开更多
AIM: To determine if the observed paracellular sucrose leak in Barrett's esophagus patients is due to their pro- ton pump inhibitor (PPI) use. METHODS: The in vivo sucrose permeability test was administered to he...AIM: To determine if the observed paracellular sucrose leak in Barrett's esophagus patients is due to their pro- ton pump inhibitor (PPI) use. METHODS: The in vivo sucrose permeability test was administered to healthy controls, to Barrett's patients and to non-Barrett's patients on continuous PPI thera- py. Degree of leak was tested for correlation with pres- ence of Barrett's, use of PPIs, and length of Barrett's segment and duration of PPI use. RESULTS: Barrett's patients manifested a near 3-fold greater, upper gastrointestinal sucrose leak than healthy controls. A decrease of sucrose leak was ob- served in Barrett's patients who ceased PPI use for 7 d.Although initial introduction of PPI use (in a PPI-na'ive population) results in dramatic increase in sucrose leak, long-term, continuous PPI use manifested a slow spon- taneous decline in leak. The sucrose leak observed in Barrett's patients showed no correlation to the amount of Barrett's tissue present in the esophagus. CONCLUSION: Although future research is needed to determine the degree of paracellular leak in actual Barrett's mucosa, the relatively high degree of leak ob- served with in vivo sucrose permeability measurement of Barrett's patients reflects their PPI use and not their Barrett's tissue perse.展开更多
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 ...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.展开更多
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 esop...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.展开更多
基金Supported by Sichuan Research Center for Coordinated Development of TCM Culture,No.2022XT12.
文摘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.
文摘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.
文摘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.
文摘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.
文摘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.
文摘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.
基金supported by Major Project of Clinical Subjects of Hospitals Afjiliated to the Ministry of Health(2007353)
文摘Objective:To investigate the efficacy and safety of the second generation argon plasma coagulation(VIO APC) in the ablation of Barrett' s Esophagus. Methods:A total of 35 patients with uncomplicated Barrett' s esophagus entered into a prospective, randomized, unblinded study comparing the treatment VIO APC combined with a proton pump inhibiter with a proton pump inhibiter administered alone. VIO APC was performed at a power setting of 40W, and argon gas flow at 1.5-2.0 L/min, and" forced" mode. Ablative treatment was repeated until either no Barrett' s epithelium remained or a maximum of 5 treatment sessions occurred. Results:In the ablation group, macroscopic complete ablation was achieved in 14 of 18 patients, and complete ablation confirmed by histology in 12 of 18 patients (P 〈 0.01). Buried glands were observed in 2 patients who had achieved macroscopic ablation. The Barrett's mucosa averaged a reduction of 65%(range 50-75%) in the remaining 4 patients. In the control group, only 2 patients had partial regression, median 30%(range 20-40%). In the ablation group, post-treatment 4 patients had transient retrosternal pain, and 3 patients had mild epigastric discomfort. One patient had a small hemorrhage during the procedure, which ceased after norepinephrine and thrombosin were administered through the endoscope biopsy channel. No adverse events were observed in the control group. During 11.8(4-15) months follow-up, patients who had achieved the complete ablation have no evidence of relapse of Barrett' s esophagus. Conclusion:VIO APC with a relatively low power setting can effectively ablate the Barrett' s mucosa. No severe adverse events were observed. Long-term follow-up is needed to assess cancer prevention and the durability of the neo-squamous epithelium.
文摘The rising incidence of esophageal adenocarcinoma(EAC) in the world has led to continued interest in its precursor lesion, Barrett' s esophagus(BE). This review endeavors to summarize the recent advances in the therapy of BE with an emphasis on novel endoscopic therapies.
基金Supported by the University of Louisville Hospital the Society for Surgery of the Alimentary Tract Career Development Award
文摘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.
文摘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.
文摘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.
基金Supported by grants from CICYT (SAF2000-0123) and Instituto de Salud Carlos Ⅲ (C03/02). Elena Piazuelo is supported by Instituto de Salud Carlos Ⅲ and Instituto Aragones de Ciencias de la Salud
文摘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.
基金Supported by Fund from Minya University, Minya, Egypt
文摘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.
文摘The natural history of Barrett's esophagus (BE) is difficult to quantify because,by definition,it should describe the course of the condition if left untreated.Pragmatically,we assume that patients with BE will receive symptomatic treatment with acid suppression,usually a proton pump inhibitor,to treat their heartburn.This paper describes the development of complications of stricture,ulcer,dysplasia and adenocarcinoma from this standpoint.Controversies over the definition of BE and its implications in clinical practice are presented.The presence of intestinal metaplasia and its relevance to cancer risk is discussed,and the need to measure the extent of the Barrett's epithelium (long and short segments) using the Prague guidelines is emphasized.Guidelines and international consensus over the diagnosis and management of BE are being regularly updated.The need for expert consensus is important due to the lack of randomized trials in this area.After searching the literature,we have tried to collate the important studies regarding progression of Barrett's to dysplasia and adenocarcinoma.No therapeutic studies yet reported show a clear reduction in the development of cancer in BE.The effect of pharmacological and surgical intervention on the natural history of Barrett's is a subject of ongoing research,including the Barrett's Oesophagus Surveillance Study and the aspirin and esomeprazole cancer chemoprevention trial with interesting results.The geographical variation and the wide range of outcomes highlight the difficulty of providing an individualized risk profile to patients with BE.Future studies on the interaction of genome wide abnormalities in Barrett's and their interaction with environmental factors may allow individualization of the risk of cancer developing in BE.
文摘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.
基金Supported by Grant-in Aid from Ministry of Education,Sports and Culture (GP Program for Basic Science),Japan
文摘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.
基金Supported by Sharpe-Strumia Research Foundation of the Bryn Mawr Hospital
文摘AIM: To determine if the observed paracellular sucrose leak in Barrett's esophagus patients is due to their pro- ton pump inhibitor (PPI) use. METHODS: The in vivo sucrose permeability test was administered to healthy controls, to Barrett's patients and to non-Barrett's patients on continuous PPI thera- py. Degree of leak was tested for correlation with pres- ence of Barrett's, use of PPIs, and length of Barrett's segment and duration of PPI use. RESULTS: Barrett's patients manifested a near 3-fold greater, upper gastrointestinal sucrose leak than healthy controls. A decrease of sucrose leak was ob- served in Barrett's patients who ceased PPI use for 7 d.Although initial introduction of PPI use (in a PPI-na'ive population) results in dramatic increase in sucrose leak, long-term, continuous PPI use manifested a slow spon- taneous decline in leak. The sucrose leak observed in Barrett's patients showed no correlation to the amount of Barrett's tissue present in the esophagus. CONCLUSION: Although future research is needed to determine the degree of paracellular leak in actual Barrett's mucosa, the relatively high degree of leak ob- served with in vivo sucrose permeability measurement of Barrett's patients reflects their PPI use and not their Barrett's tissue perse.
基金Supported by National Health and Medical Research Council, Australia
文摘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.
基金Supported by GI SPORE Grant p50 CA95060 from the National Cancer Institute, to Dvorak K
文摘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.