Adenocarcinoma risk in patients registered with Polish Barrett's Oesophagus Registry.

Barrett's Oesophagus (BO) is a complication of chronic gastro-oesophageal reflux disease (GORD) and is a major risk factor for oesophageal adenocarcinoma. Current guidelines are based on data showing a 0.5% annual malignancy progression rate. The Polish Barrett's Oesophagus Registry (POBOR) was established to characterize Polish patients with BO and estimate the risk of malignant progression. POBOR was established in 1999 after a dedicated training of endoscopists and histopathologists. Physicians registered patients using a dedicated registry form. After excluding patients known to have endoscopic treatment for BO, follow-up <1 year and adenocarcinoma found at index endoscopy we have linked patients personal identification numbers (PESEL) with the National Cancer Registry to identify those with a diagnosis of oesophageal or gastric cardia adenocarcinoma. In total, 843 patients were registered [609 men (72.2%), male to female ratio 2.6:1] with median age at diagnosis of 56 years (IQR:47-67). Long segment BE was found at index endoscopy in 294 patients (39.4%) whereas low grade dysplasia in 147 (17.4%). 112 patients (13.3%) fulfilled the exclusion criteria and the remaining 731 were followed for a median of 9.8 years (IQR: 9.3-10.0). After 6779 patient-years, 6 adenocarcinomas were diagnosed yielding an incidence rate of 0.89 per 1000 patients-years (95% confidence interval [CI 0.40-1.97]) which corresponds to annual malignancy progression rate of less than 0.1%. The malignancy rate in patients with low grade dysplasia was 3.70 per 1000 patient-years (95% CI 1.39-9.85). In Polish BO patients the risk of malignant progression was lower than previously reported. It was notably higher in patients with low grade dysplasia than in those with no dysplasia at index endoscopy, which may warrant strict surveillance in these patients.

Narrow-band imaging vs Lugol chromoendoscopy in screening for esophageal squamous cell neoplasia: a randomized trial.

INTRODUCTION: To date, there is no established optimal method for endoscopic detection of esophageal squamous cell neoplasia in high­risk individuals. OBJECTIVES: We aimed to compare the performance of narrow­band imaging (NBI) and Lugol chromoendoscopy in screening for esophageal neoplasia among patients with a history of treatment for head and neck squamous cell cancer (HNSCC). PATIENTS AND METHODS: We randomly assigned 300 patients who had completed curative treatment for HNSCC at least 1 year prior to the inclusion to undergo either NBI or Lugol endoscopy (2:1 ratio). Following white­light examination of the esophagus, the assigned imaging study was performed, and biopsies were taken from any suspicious lesions identified using NBI or Lugol chromoendoscopy. The primary end point was positive predictive value (PPV) of the biopsied lesion for a diagnosis of esophageal neoplasia (high­grade intraepithelial neoplasia [HG­IEN] or invasive esophageal squamous cell carcinoma [ESCC]). The secondary end points included the number of biopsied lesions, duration of esophagus examination, and endoscopy tolerance. RESULTS: In 294 patients included in the final analysis (NBI, n = 204; Lugol chromoendoscopy, n = 90), we diagnosed 3 ESCCs (1.02%) and 2 HG­IENs (0.68%). The PPV of NBI and Lugol chromoendoscopy in per­lesion analysis was 7.69% (95% CI, 0.94%-25.1%) and 8.11% (95% CI, 1.7%-21.9%), respectively (P >0.99). NBI outperformed Lugol chromoendoscopy in terms of the rate of patients requiring biopsy (12.75% vs 41.11%; P = 0.003), duration of esophagus examination (3.5 min vs 5.15 min; P <0.001), and endoscopy tolerance assessed on the visual analog scale (25 mm vs 36.5 mm; P = 0.002). CONCLUSIONS: With a PPV comparable to that of Lugol chromoendoscopy, but a lower number of biopsies required, shorter examination time, and better patient tolerance, NBI could be considered the primary screening method for ESCC in patients with HNSCC.

Large intra- and inter-individual variability of genes expression levels limits potential predictive value of molecular diagnosis of dysplasia in Barrett's esophagus.

Barrett's esophagus represents a well-defined precursor lesion of esophageal adenocarcinoma, although only a subset of patients with these lesions advances to invasive cancer. Currently, reliable markers predicting neoplastic progression in Barrett's esophagus are lacking. The only clinically useful risk factor is the presence of dysplasia in Barrett's epithelium, but its use as a prognostic marker of disease progression has several significant limitations. Thus, identification of biomarkers of potential prognostic value in dysplasia development in Barrett's esophagus is highly important. The aim of the study was to determine if expression levels of selected genes support histologic diagnosis of dysplastic changes in Barrett's esophagus. Upon rigorous sampling and independent histopathologic examination of endoscopic specimens by two experienced gastrointestinal pathologists, 56 patients with Barrett's esophagus (16 negative for dysplasia, 15 with indefinite, 21 with low-grade, and 4 with high-grade dysplasia) were selected for molecular analysis. The relative mRNA levels of ten selected genes were estimated by quantitative real-time polymerase chain reaction (PCR) analysis. Although expression of nine genes showed trends toward down- or upregulation during progression from Barrett's esophagus without dysplasia to Barrett's esophagus with high-grade dysplasia, only a decrease in S100A2 mRNA levels was statistically significant (P<0.05). However, there was considerable variation among individuals and significant overlapping of ranges. Furthermore, detailed, comparative analysis of serial samples from Barrett's mucosa and normal squamous epithelium shows large intra-individual variability of gene expression levels. In conclusion, expression of this set of ten genes cannot be used as a molecular marker aiding histological examination of dysplasia in Barrett's esophagus. Significant inter- and intra-patient variations of gene expression levels makes use of the selected genes impractical.

Three clinical variants of gastroesophageal reflux disease form two distinct gene expression signatures.

It has been proposed recently that gastroesophageal reflux disease (GERD) patients may be categorized into three distinct groups exhibiting non-erosive reflux disease (NERD), erosive reflux disease (ERD), and Barrett's esophagus (BE). Measurement of relative gene expression levels was undertaken to identify distinct molecular subclasses in different variants of gastroesophageal disease. The measurements were made with Affymetrix U133A 2.0 GeneChips and RNA isolated from mucosal samples of normal squamous esophageal epithelium from 24, 28, and 26 patients with NERD, ERD and BE, respectively. Statistical testing of microarray data showed that gene expression profiles are discriminative for BE and NERD, but not for combinations of BE and ERD or NERD and ERD. In addition, women developing NERD exhibited transcriptional patterns that differed from those of men with BE. In clustering analyses, we did not observe correlations between sex and assignment of gene expression profile of ERD patients to either the NERD or the BE group. Although the biological significance of the identified genes remains uncertain, we hypothesize that GERD is a monophyletic disease that develops with the onset of gastroesophageal reflux and represents two main molecular classes, which may result in different progressions to inflammatory process within esophageal epithelium modulated by sexual dimorphism. While normal epithelium samples from NERD and BE patients are molecularly homogeneous, esophageal mucosa from ERD patients is molecularly similar to either NERD or BE. These findings may be useful for defining molecular markers which could predict potential progression to Barrett's metaplasia among patients with reflux disease.