No abstract

Aberrant crypt foci (ACF) are the earliest morphologically identifiable lesions in the colon that can be detected by high-definition chromoendoscopy with contrast dye spray. Although frequently associated with synchronous adenomas, their role in colorectal tumor development, particularly in the proximal colon, is still not clear. The goal of this study was to evaluate the profile of colon-adherent bacteria associated with proximal ACF and to investigate their relationship to the presence and subtype of synchronous polyps present throughout the colon. Forty-five subjects undergoing a screening or surveillance colonoscopy were included in this retrospective study. Bacterial cells adherent to the epithelia of ACF and normal mucosal biopsies were visualized by in situ hybridization within confocal tissue sections. ACF showed significantly greater heterogeneity in their bacterial microbiome profiles compared with normal mucosa. One of the bacterial community structures we characterized was strongly correlated with the presence of synchronous polyps. Finally, using DNA mass spectrometry to evaluate a panel of colorectal cancer hotspot mutations present in the ACF, we found that three APC gene mutations were positively associated with the presence of Instestinibacter sp., whereas KRAS mutations were positively correlated with Ruminococcus gnavus. This result indicates a potential relationship between specific colon-associated bacterial species and somatically acquired CRC-related mutations. Overall, our findings suggest that perturbations to the normal adherent mucosal flora may constitute a risk factor for early neoplasia, demonstrating the potential impact of mucosal dysbiosis on the tissue microenvironment and behavior of ACF that may facilitate their progression towards more advanced forms of neoplasia.

No abstract

Our understanding of diverticular disease has evolved significantly during the last 25 years, and as such, a reexamination is in order. We performed a literature search for the years 1960-2017 of PubMed, Medline, and Google Scholar for updates regarding the epidemiology, risk factors, and therapies for traditional diverticulitis as well as the recently described subtypes of diverticular disease, segmental colitis associated with diverticulosis, and symptomatic uncomplicated diverticular disease. Although the prevalence of diverticulosis is still extremely common in the general population, the literature suggests that the incidence of diverticulitis is much less than previously believed and occurrences do not necessarily increase with age. In addition, the commonly held beliefs that low-fiber diets alone contribute to the development of diverticulosis and diverticulitis have not been verified; however, the combination of a low-fiber diet and a high red meat/high-fat diet is a risk factor for diverticulitis. Surgery continues to be the treatment for severe complications of diverticulitis, but new literature suggests that it has a poor utility in preventing a recurrence of diverticulitis in the long term; therefore, elective surgery after two episodes of diverticulitis is no longer the standard.

Aberrant crypt foci (ACF) are the earliest morphologically identifiable lesion in the colon that can be detected by high-definition chromoendoscopy with contrast dye-spray. Although frequently associated with synchronous adenomas, their role in colorectal tumor development, particularly in the proximal colon, is still not clear. The goal of this study was to evaluate the profile of colon-associated bacteria associated with proximal ACF and to investigate their relationship to the presence and subtype of synchronous polyps present throughout the colon. Forty-five subjects undergoing a screening or surveillance colonoscopy were included in this retrospective study. Our study cohort included a total of 16 subjects with no identifiable proximal lesions (either ACF or polyp), 14 subjects with at least 1 ACF but no polyp(s), and 15 subjects with both at least 1 ACF and a synchronous proximal polyp(s) detected at colonoscopy. Bacterial cells adherent to the epithelia of ACF and normal mucosa were visualized by in situ hybridization within confocal sections. Bacterial DNA isolated from biopsies was used to construct PCR amplicon libraries targeting the V4 hypervariable region of the 16S rRNA gene, which were then sequenced on the Illumina platform. ACF showed significantly greater heterogeneity in their bacterial profiles compared to normal mucosa. Interestingly, one of the bacterial community structures we characterized was strongly correlated with the presence of synchronous polyps. The observed dysbiosis is more prominent within the colonic epithelium that also harbors synchronous polyps. Finally using DNA-mass spectrometry to evaluate a panel of colorectal cancer hot-spot mutations present in the ACF, we found that several APC gene mutations (R1450*, R876*, S1465fs*3) were positively associated with the presence of Instestinibacter sp., whereas KRAS mutations (G12V, G12D) were positively correlated with Ruminococcus gnavus. This result indicates a potential relationship between specific colonassociated bacterial species and somatically acquired CRC-related mutations. Overall, our findings suggest that perturbations to the normal adherent mucosal flora may constitute a risk factor for early neoplasia, either facilitating (or impeding) the progression of small lesions to more advanced forms of neoplasia.