Damage-associated molecular patterns in inflammatory bowel disease:From biomarkers to therapeutic targets

The chronic inflammatory process underlying inflammatory bowel disease (IBD), comprising Crohn's disease and ulcerative colitis, derives from the interplay of several components in a genetically susceptible host. These components include environmental elements and gut microbiota a dysbiosis. For decades, immune abnormalities have been investigated as critically important in IBD pathogenesis, and attempts to develop effective therapies have predominantly targeted the immune system. Nevertheless, immune events represent only one of the constituents contributing to IBD pathogenesis within the context of the complex cellular and molecular network underlying chronic intestinal inflammation. These factors need to be appreciated within the milieu of nonimmune components. Damage-associated molecular patterns (DAMPs), which are essentially endogenous stress proteins expressed or released as a result of cell or tissue damage, have been shown to act as direct proinflammatory mediators. Excessive or persistent signalling mediated by such molecules can underlie several chronic inflammatory disorders, including IBD. The release of endogenous DAMPs amplifies the inflammatory response driven by immune and non-immune cells and promotes epigenetic reprogramming in IBD.The effects determine pathologic changes,which may sustain chronic intestinal inflammation and also underlie specific disease phenotypes.In addition to highlighting the potential use of DAMPs such as calprotectin as biomarkers,research on DAMPs may reveal novel mechanistic associations in IBD pathogenesis and is expected to uncover putative therapeutic targets.

Body mass index and colon cancer screening:The road ahead

Screening for colorectal cancer(CRC) has been associated with a decreased incidence and mortality from CRC.However,patient adherence to screening is less than desirable and resources are limited even indeveloped countries.Better identification of individuals at a higher risk could result in improved screening efforts.Over the past few years,formulas have been developed to predict the likelihood of developing advanced colonic neoplasia in susceptible individuals but have yet to be utilized in mass screening practices.These models use a number of clinical factors that have been associated with colonic neoplasia including the body mass index(BMI).Advances in our understanding of the mechanisms by which obesity contributes to colonic neoplasia as well as clinical studies on this subject have proven the association between BMI and colonic neoplasia.However,there are still controversies on this subject as some studies have arrived at different conclusions on the influence of BMI by gender.Future studies should aim at resolving these discrepancies in order to improve the efficiency of screening strategies.

Role of high definition colonoscopy in colorectal adenomatous polyp detection

AIM:To investigate the rates of polyp detection in a mixed risk population using standard definition (SDC) vs high definition colonoscopes (HDC).METHODS:This was a retrospective cohort comparative study of 3 colonoscopists who each consecutively performed 150 SDC (307,200 pixel) and 150 HDC (792,576 pixels) in a community teaching hospital.RESULTS:A total of 900 colonoscopies were evaluated (mean age 56,46.8% men),450 with each resolution.Polyps of any type were detected in 46.0% of patients using SDC and 43.3% with HDC (P=0.42).There was no significant difference between the overall number of polyps,HDC (397) and SDC (410),detected among all patients examined,(P=0.73).One or more adenomatous polyps were detected in 24.2% of patients with HDC and 24.9% of patients with SDC colonoscopy (P=0.82).There was no significant difference between HDC (M=0.41) and SDC (M=0.42) regarding adenomatous polyp (P=0.88) or advanced adenoma (P=0.56) detection rate among all patients examined.CONCLUSION:HDC did not improve yield of adenomatous polyp,advanced adenoma or overall polyp detection in a population of individuals with mixed risk for colorectal cancer.