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Background Colon cancer (CC) is the third most common cancer worldwide, highlighting the importance of developing effective prevention strategies. Accumulating evidence supports that aspirin use reduces CC incidence. We reported previously that aspirin suppresses age-associated and CC-relevant DNA methylation (DNAm) in healthy colon. Here we addressed the aspirin’s effectiveness in longitudinal cohort. Methods We measured genome-wide DNAm in 124 healthy normal mucosa samples taken at baseline (time point 1, t1) and after 10-years follow-up (time point 2, t2) from a longitudinal female screening cohort. We investigated the time-dependent methylation drift in aspirin users and nonusers using multivariable regression and related the modulatory effect of aspirin to colonic epigenome-aging and CC. Results Over time, compared to nonusers, long-term (≥ 2 years) aspirin users showed less hypermethylated CpGs (proximal: 17% vs. 87%; distal: 16% vs. 70%) and more hypomethylated CpGs (proximal: 83% vs. 13%; distal: 84% vs. 30%). Overall, users showed 2% (P = 0.02) less mean methylation levels than nonusers in proximal colon and displayed repressed methylation age (mAge). Methylation loss in users occurred at several CC-specific tumor suppressors that gained methylation in nonusers. Methylation loss in users effected genes involved in immune system and inflammation, while methylation gain in nonusers effected genes involved in metabolism. Conclusions This is the first longitudinal study demonstrating effectiveness of aspirin-use in suppression of age-related and CC-relevant hypermethylation in the normal colon. These findings provide a rationale for future studies to evaluate loci that may serve as markers to identify individuals that will benefit most from aspirin and hence increase its efficiency in CC prevention and therapy.

Colorectal cancer screening guidelines are identical for men and women despite reported differences in epidemiology, endoscopy performance, screening preferences, and screening uptake. High-quality research is needed to determine whether gender aspects may in real world increase acceptance and overcome screening barriers, which may lead to better use of limited resources allocated for public health.

In light of the huge population at risk for colorectal cancer (CRC) and limited screening resources, shifting the use of screening tests from low-risk to high-risk groups is a valid option. This study reviews the gender of potential screenees as a factor influencing CRC screening yield and overall results. The higher risk of advanced neoplasia, better endoscopy performance, and greater endoscopy screening uptake in men should be taken into consideration when planning an optimized CRC screening program.

This article summarizes the most important recent articles on colonoscopy as a screening tool for colorectal cancer, presenting screening outcomes and quality issues. We also refer to the first published results of CT colonography screening in the United States and cost-effectiveness analyses of this method. Also discussed are recent progress in fecal DNA testing and studies of the impact of screening on mortality and lifestyle.

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

Barrett's esophagus is characterized by the replacement of squamous epithelium with specialized intestinal metaplastic mucosa. The exact mechanisms of initiation and development of Barrett's metaplasia remain unknown, but a hypothesis of "successful adaptation" against noxious reflux components has been proposed. To search for the repertoire of adaptation mechanisms of Barrett's metaplasia, we employed high-throughput functional genomic and proteomic methods that defined the molecular background of metaplastic mucosa resistance to reflux. Transcriptional profiling was established for 23 pairs of esophageal squamous epithelium and Barrett's metaplasia tissue samples using Affymetrix U133A 2.0 GeneChips and validated by quantitative real-time polymerase chain reaction. Differences in protein composition were assessed by electrophoretic and mass-spectrometry-based methods. Among 2,822 genes differentially expressed between Barrett's metaplasia and squamous epithelium, we observed significantly overexpressed metaplastic mucosa genes that encode cytokines and growth factors, constituents of extracellular matrix, basement membrane and tight junctions, and proteins involved in prostaglandin and phosphoinositol metabolism, nitric oxide production, and bioenergetics. Their expression likely reflects defense and repair responses of metaplastic mucosa, whereas overexpression of genes encoding heat shock proteins and several protein kinases in squamous epithelium may reflect lower resistance of normal esophageal epithelium than Barrett's metaplasia to reflux components. Despite the methodological and interpretative difficulties in data analyses discussed in this paper, our studies confirm that Barrett's metaplasia may be regarded as a specific microevolution allowing for accumulation of mucosal morphological and physiological changes that better protect against reflux injury.

There is no direct evidence that colonoscopy screening reduces mortality from colorectal cancer. However, results from studies using fecal occult blood testing and sigmoidoscopy, along with the fact that colonoscopy is performed after positive primary screening tests, support this assumption. Colonoscopy every 10 years is the preferred strategy in terms of clinical outcomes and cost effectiveness. The purpose of this article is to present the methodology used for the implementation of an opportunistic colonoscopy colorectal cancer screening program in Poland. We also review recent literature on challenges related to colonoscopy screening including recruitment, acceptance, and quality of the procedure.

Photodynamic therapy (PDT) using 5-aminolaevulinic-acid-(ALA)-induced protoporphyrin IX (PPIX) increases survival in hamsters with pancreatic cancer. However, experiments with other photosensitizers on this model show a high risk of duodenal perforation. In this paper, the pharmacokinetics and PDT effects of ALA on normal tissues in the pancreatobiliary region are presented. Using quantitative fluorescence microscopy, maximum PPIX fluorescence was seen in the bile ducts, less in the duodenal mucosa and least in the muscularis propria and pancreas. For PDT, light was delivered either using a bare fibre touching the tissue (single-point illumination), or irradiating a 1.5 cm diameter circular area. Single-point PDT (50 J) produced only localized reversible damage without perforation. Surface irradiation of the whole periampullary region (50 J cm−2) caused extensive damage, sometimes with perforation. Before PDT can be used safely to treat tumours of the pancreas and bile duct, further studies are necessary to understand its effect on larger areas of normal tissue.