Differential gene expression in normal esophagus and Barrett’s esophagus

Purpose  

As the premalignant lesion of human esophageal adenocarcinoma (EAC), Barrett’s esophagus (BE) is characterized by intestinal metaplasia in the normal esophagus (NE). Gene expression profiling with microarray and serial analysis of gene expression (SAGE) may help us understand the potential molecular mechanism of human BE.     

Recurrent Barrett's esophagus and adenocarcinoma after esophagectomy

Background  

Esophagectomy is considered the gold standard for the treatment of high-grade dysplasia in Barrett's esophagus (BE) and for noninvasive adenocarcinoma (ACA) of the distal esophagus. If all of the metaplastic epithelium is removed, the patient is considered "cured". Despite this, BE has been reported in patients who have previously undergone esophagectomy. It is often debated whether this is "new" BE or the result of an esophagectomy that did not include a sufficiently proximal margin. Our aim was to determine if BE recurred in esophagectomy patients where the entire segment of BE had been removed.     

Frequency and Risk Factors for Barrett’s Esophagus in Taiwanese Patients: A Prospective Study in a Tertiary Referral Center

Background  

There is a paucity of epidemiologic data concerning Barrett’s esophagus (BE) in Taiwan.     

CagA-positive Helicobacter pylori infection is not associated with decreased risk of Barrett's esophagus in a population with high H. pylori infection rate

Background & aim  

The role that H. pylori infection plays in the development of and Barrett's esophagus (BE) is uncertain. We tested the hypothesis that infection with cagA+ Helicobacter pylori strains protects against the development of BE.     

Comparison of Endoscopic and Clinical Characteristics of Patients with Familial and Sporadic Barrett’s Esophagus

Background  

A proportion of Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) displays familial aggregation, known as familial Barrett’s esophagus (FBE). Pedigrees and characteristics of EAC in these families have been previously described.     

Prevalence and risk factors of Barrett's esophagus in patients undergoing endoscopy for upper gastrointestinal symptoms

OBJECTIVE: To investigate the prevalence of Barrett's esophagus (BE) and its risk factors in patients undergoing endoscopy for upper gastrointestinal symptoms in a Chinese tertiary referral medical center. METHODS: All consecutive patients receiving an endoscopy for upper gastrointestinal symptoms in our medical center from September to December 2007 were recruited. BE was explored for at endoscopy when a suspected columnar-lined esophagus was found. Patients with specialized intestinal metaplasia in the distal esophagus were defined as having BE. RESULTS: A total of 2022 patients (1053 male and 969 female) were recruited. The patients were aged 18 to 88 years and with a mean age of 46.97 ± 14.84 years. BE was found in 21 patients (15 male and 6 female), a prevalence of 1.0% of all patients receiving endoscopy for upper gastrointestinal symptoms in our medical center. One of the 21 patients had low-grade dysplasia. By logistic multivariate analysis, age (OR 1.03; 95% CI, 1.00, 1.07) and reflux esophagitis (OR 4.44; 95% CI, 1.22, 16.17) were factors associated significantly with BE. CONCLUSION: The prevalence of BE in our study was lower than that reported in other studies, especially in studies from developed countries. Older age and reflux esophagitis may be the risk factors for developing BE.     

Computer-Assisted Analysis of Abrasive Transepithelial Brush Biopsies Increases the Effectiveness of Esophageal Screening: A Multicenter Prospective Clinical Trial by the EndoCDx Collaborative Group

Background  

The sensitivity of screening for Barrett’s esophagus (BE) and esophageal dysplasia (ED) is hampered by the limited amount of tissue that can be sampled by forceps biopsy (FB).     

Prague C&M and Japanese criteria: shades of Barrett’s esophagus endoscopic diagnosis

Background  

The anatomical reference points used to endoscopically diagnose Barrett’s esophagus (BE) differ between Japan and other countries. The esophageal gastric junction (EGJ) is defined as the distal limit of the lower esophageal longitudinal or palisade vessels in Japan, but as the proximal margin of the gastric folds (Prague C&M criteria). The aim of this study was to prospectively compare endoscopic BE diagnoses using the Japanese and Prague C&M criteria.     

Oral Bisphosphonate Prescriptions and the Risk of Esophageal Adenocarcinoma in Patients with Barrett’s Esophagus

Background  

Recent case reports suggested a link between oral bisphosphonate use and esophageal cancer. We therefore examined the association between these medications and the risk of esophageal adenocarcinoma (EAC) in patients with Barrett’s esophagus (BE).     

Prevalence of Barrett’s Esophagus in Patients with or without GERD Symptoms: Role of Race, Age, and Gender

Background Gastroesophageal reflux disease is associated with a significantly increased risk of Barrett’s esophagus (BE) and adenocarcinoma of the esophagus. Racial differences in the prevalence of BE are controversial. Our purpose was to study the prevalence of Barrett’s esophagus in patients with and without gastroesophageal reflux disease (GERD) symptoms, and the differences between these two groups in terms of race, age, and sex. Methods Esophagogastroduodenoscopy (EGD) reports from the PENTAX EndoPRO database for the Endoscopy Unit at the University of Texas Medical Branch from 2005 to 2007 were reviewed. Four hundred and ten patients who underwent upper endoscopy because of GERD symptoms that were not responding to proton pump inhibitor (PPI) therapy or with alarm symptoms and 4,047 patients undergoing upper endoscopy for other reasons without GERD symptoms were identified. Results BE was significantly more common among males. The prevalence of BE was higher in patients with GERD symptoms than those without GERD symptoms. Overall, more cases of BE, dysplasia, and adenocarcinoma were found among the patients without GERD symptoms than those that underwent endoscopy because of GERD symptoms. The prevalence of BE among Caucasian, African American, Hispanic, and “other” groups with GERD symptoms were 5%, 2.56%, 4.4%, and 0%, respectively. The prevalence of BE among these racial groups without GERD symptoms were 1.9%, 0.9%, 1.57%, and 0.8%, respectively. The association between race and BE was not statistically significant (df = 3, P = 0.2628), including after adjusting for the presence of GERD symptoms (df = 3, P = 0.2947). Patients without GERD symptoms that presented with BE were significantly older than the patients without BE (P < 0.01). Conclusions BE is a male-dominant disease. The prevalence of Barrett’s esophagus was not significant different among Caucasian, Hispanics, and African Americans. Most of the patients with BE, dysplasia, and adenocarcinoma did not have GERD symptoms. X. Fan contributed to the concept and design of the study, the analysis and interpretation of the data, and the drafting of this article. N. Snyder contributed to the critical revision of the article for important intellectual content and final approval of this article.     

Secular Trends in Patients Diagnosed with Barrett’s Esophagus

Background  

It is not known whether there have been recent changes in demographic or clinical characteristics among patients newly diagnosed with Barrett’s esophagus (BE), which could be a result of changes in disease epidemiology or of screening or surveillance effects, and could have clinical implications.     

Detection of Intestinal Metaplasia After Successful Eradication of Barrett’s Esophagus with Radiofrequency Ablation

Background  

Radiofrequency ablation (RFA) is an effective means of eradicating Barrett’s esophagus (BE), both with and without associated dysplasia. Several studies have documented high initial success rates with RFA. However, there is limited data on IM detection rates after eradication.     

Expression of IFN-γ and IL-4 in the Esophageal Mucosa of Patients with Reflux Esophagitis and Barrett’s Esophagus and Their Relationship with Endoscopic and Histologic Grading

Introduction  

This study investigated the expression of interferon-γ (IFN-γ) and interleukin-4 (IL-4) in the esophageal biopsies from patients with reflux esophagitis (RE) and Barrett’s esophagus (BE) and their relationships with endoscopic grading and histologic grading.     

Esophageal Helicobacter pylori colonization aggravates esophageal injury caused by reflux

AIM: To investigate esophageal Helicobacter pylori (H. pylori) colonization on esophageal injury caused by reflux and the related mechanisms.METHODS: An esophagitis model, with acid and bile reflux, was surgically produced in male rats. The rats were randomly divided into either: (1) an esophagogastroduodenal anastomosis (EGDA) group; (2) an EGDA with H. pylori infection group; (3) a pseudo-operation with H. pylori infection group; or (4) a pseudo-operation group. All rats were kept for 36 wk. Based on the location of H. pylori colonization, the EGDA rats with H. pylori infection were subdivided into those with concomitant esophageal H. pylori colonization or those with only gastric H. pylori colonization. The esophageal injuries were evaluated grossly and microscopically. The expressions of CDX2 and MUC2 were determined by real-time polymerase chain reaction (RT-PCR) and immunohistochemistry. Ki-67 antigen expression was determined by immunohistochemistry. The mRNA levels of cyclin D1, c-Myc, Bax and Bcl-2 were determined by RT-PCR. Cell apoptosis was evaluated using the TdT-mediated dUTP nick-end labeling method.RESULTS: Esophagitis, Barrett’s esophagus (BE), and esophageal adenocarcinoma (EAC) developed in rats that underwent EGDA. When comparing rats with EGDA and concomitant esophageal H. pylori colonization to EGDA-only rats, the severity of injury (87.9 ± 5.2 vs 77.2 ± 8.6, macroscopically, 92.5 ± 8.0 vs 83.8 ± 5.5, microscopically, both P < 0.05) and the incidences of BE (80.0% vs 33.3%, P = 0.055) and EAC (60.0% vs 11.1%, P < 0.05) were increased. These increases were associated with upregulation of CDX2 and MUC2 mRNA (10.1 ± 5.4 vs 3.0 ± 2.9, 8.4 ± 4.6 vs 2.0 ± 3.2, respectively, Ps < 0.01) and protein (8.1 ± 2.3 vs 3.3 ± 3.1, 7.3 ± 4.0 vs 1.8 ± 2.7, respectively, all P < 0.05). The expression of Ki-67 (8.9 ± 0.7 vs 6.0 ± 1.7, P < 0.01) and the presence of apoptotic cells (8.3 ± 1.1 vs 5.3 ± 1.7, P < 0.01) were also increased significantly in rats with EGDA and concomitant esophageal H. pylori colonization compared with rats with EGDA only. The mRNA levels of cyclin D1 (5.8 ± 1.9 vs 3.4 ± 1.3, P < 0.01), c-Myc (6.4 ± 1.7 vs 3.7 ± 1.2, P < 0.01), and Bax (8.6 ± 1.6 vs 5.1 ± 1.3, P < 0.01) were significantly increased, whereas the mRNA level of Bcl-2 (0.6 ± 0.3 vs 0.8 ± 0.3, P < 0.01) was significantly reduced in rats with EGDA and concomitant esophageal H. pylori colonization compared with rats with EGDA only.CONCLUSION: Esophageal H. pylori colonization increases esophagitis severity, and facilitates the development of BE and EAC with the augmentation of cell proliferation and apoptosis in esophageal mucosa.     

MicroRNA Expression Differentiates Squamous Epithelium from Barrett’s Esophagus and Esophageal Cancer

Background

Current strategies fail to identify most patients with esophageal adenocarcinoma (EAC) before the disease becomes advanced and incurable. Given the dismal prognosis associated with EAC, improvements in detection of early-stage esophageal neoplasia are needed.

Aim

We sought to assess whether differential expression of microRNAs could discriminate between squamous epithelium, Barrett’s esophagus (BE), and EAC.

Methods

We analyzed microRNA expression in a discovery cohort of human endoscopic biopsy samples from 36 patients representing normal squamous esophagus (n = 11), BE (n = 14), and high-grade dysplasia/EAC (n = 11). RNA was assessed using microarrays representing 847 human microRNAs followed by quantitative real-time polymerase chain reaction (qRT-PCR) verification of nine microRNAs. In a second cohort (n = 18), qRT-PCR validation of five miRNAs was performed. Expression of 59 microRNAs associated with BE/EAC in the literature was assessed in our training cohort. Known esophageal cell lines were used to compare miRNA expression to tissue miRNAs.

Results

After controlling for multiple comparisons, we found 34 miRNAs differentially expressed between squamous esophagus and BE/EAC by microarray analysis. However, miRNA expression did not reliably differentiate non-dysplastic BE from EAC. In the validation cohort, all five microRNAs selected for qRT-PCR validation differentiated between squamous samples and BE/EAC. Microarray results supported 14 of the previously reported microRNAs associated with BE/EAC in the literature. Cell lines did not generally reflect miRNA expression found in vivo.

Conclusions

These data indicate that miRNAs differ between squamous esophageal epithelium and BE/EAC, but do not distinguish between BE and EAC. We suggest prospective evaluation of miRNAs in patients at high risk for EAC.     

Toll-like receptor 4 activation in Barrett’s esophagus results in a strong increase in COX-2 expression

Background

Barrett’s esophagus (BE) is known to progress to esophageal adenocarcinoma in a setting of chronic inflammation. Toll-like receptor (TLR) 4 has been linked to inflammation-associated carcinogenesis. We aimed to determine the expression and functional activity of TLR4 in the esophagus and whether TLR4 activation in BE could promote carcinogenesis by inducing COX-2 expression.

Methods

TLR4 expression in esophageal adenocarcinoma, BE, duodenum, reflux esophagitis and normal squamous esophagus biopsies was assessed using real-time PCR and validated by in situ hybridization and immunohistochemistry. Ex vivo cultures of BE, duodenum and normal squamous esophagus biopsies and a BE cell line (BAR-T) were stimulated with the TLR4 agonist lipopolysaccharide (LPS). To evaluate the effect of TLR4 activation, NF-κB activation, IL8 secretion and expression and COX-2 expression were determined.

Results

TLR4 expression was significantly increased in esophageal adenocarcinoma, BE, duodenum and reflux esophagitis compared to normal squamous esophagus. LPS stimulation resulted in NF-κB activation and a dose-dependent increase of IL8 secretion and mRNA expression. The induction of IL8 was more evident in BE compared to normal squamous esophagus. Upon LPS stimulation, COX-2 expression increased significantly in ex vivo cultured BE biopsies, which was observed in both epithelium and lamina propria cells. However, no effect was found in duodenum and normal squamous esophagus biopsies.

Conclusion

TLR4 activation in BE results in a strong increase in COX-2 and may contribute to malignant transformation.     

Gastroesophageal reflux leads to esophageal cancer in a surgical model with mice

Background  

Esophago-gastroduodenal anastomosis with rats mimics the development of human Barrett's esophagus and esophageal adenocarcinoma by introducing mixed reflux of gastric and duodenal contents into the esophagus. However, use of this rat model for mechanistic and chemopreventive studies is limited due to lack of genetically modified rat strains. Therefore, a mouse model of esophageal adenocarcinoma is needed.     

The development and validation of an endoscopic grading system for Barrett's esophagus: the Prague C & M criteria

BACKGROUND & AIMS: Barrett's esophagus (BE) is a premalignant condition for esophageal adenocarcinoma, its diagnosis relying initially on recognition of a columnar-lined distal esophagus. We aimed to develop and validate explicit, consensus-driven criteria for the endoscopic diagnosis and grading of BE. METHODS: An international working group agreed on criteria and developed materials for their formal evaluation using video-endoscopic recordings gathered in a standardized manner in 29 patients. The criteria included assessment of the circumferential (C) and maximum (M) extent of the endoscopically visualized BE segment as well as endoscopic landmarks. The recordings were scored according to these criteria by a separate international panel of 29 endoscopists. RESULTS: The Prague C & M Criteria give explicit guidance on the endoscopic recognition of BE and grading of its extent. The overall reliability coefficients (RC) for the assessment of the C & M extent of the endoscopic BE segment above the gastroesophageal junction were 0.95 and 0.94, respectively. The rates of exact agreement (for C & M values) for pairwise comparisons of individual patient values were 53% and 38%, respectively, whereas the values for agreement within a 2-cm interval were 97% and 95%, respectively. The overall RC for endoscopic recognition of BE >/=1 cm was 0.72, whereas for BE <1 cm, it was 0.22. The RCs for recognizing the location of the gastroesophageal junction and the diaphragmatic hiatus were 0.88 and 0.85, respectively. CONCLUSIONS: The Prague C & M Criteria have high overall validity for the endoscopic assessment of visualized BE lengths.     

Radiofrequency Ablation for Dysplasia in Barrett’s Esophagus Restores β-Catenin Activation Within Esophageal Progenitor Cells

Background and Aims  

Endoscopic therapies for Barrett’s esophagus (BE) associated dysplasia, particularly radiofrequency ablation (RFA), are popular alternatives to surgery. The effect of such therapies on dysplastic stem/progenitor cells (SPC) is unknown. Recent studies suggest that AKT phosphorylation of β-Catenin occurs in SPCs and may be a marker of activated SPCs. We evaluate the effect of RFA in restoring AKT-mediated β-Catenin signaling in regenerative epithelium.     

Diagnosis of endoscopic Barrett’s esophagus by transnasal flexible spectral imaging color enhancement

Background  

The diagnosis of endoscopic Barrett’s esophagus (BE) has been under discussion for the past decade because palisade vessels may be obscured by inflammation or the location of upper end of gastric fold may be diversely changed. The flexible spectral imaging color enhancement (FICE) system can reconstruct improved spectral images decomposed from ordinary endoscopic images with free selection of three wavelengths, and can provide non-magnified images with high light intensity.