The human intestine retains a complex microbial ecosystem, which performs crucial functions that impact on host health. Several studies have indicated that intestinal dysbiosis may impact on the establishment of life-threatening intestinal diseases such as colorectal cancer. An adenomatous polyp is the result of abnormal tissue growth, which is benign but is considered to be associated with a high risk of developing colorectal cancer, based on its grade of dysplasia. Development of diagnostic tools that are based on surveying the gut microbiota and are aimed at early detection of colorectal cancer represent highly desirable target. For this purpose, we performed a pilot study in which we applied a metataxonomic analysis based on 16S rRNA gene sequencing approach to unveil the composition of microbial communities of intestinal polyps. Moreover, we performed a meta-analysis involving the reconstructed microbiota composition of adenomatous polyps and publicly available metagenomics datasets of colorectal cancer. These analyses allowed the identification of microbial taxa such as Faecalibacterium, Bacteroides and Romboutsia, which appear to be depleted in cancerogenic mucosa as well as in adenomatous polyps, thus representing novel microbial biomarkers associated with early tumor formation. Furthermore, an absolute quantification of Fusubacterium nucleatum in polyps further compounded the important role of this microorganism as a valuable putative microbial biomarker for early diagnosis of colorectal cancer.
Microsatellites are short tandem repeat DNA sequences of one to tetra base pairs distributed throughout the human genome, both in coding and non-coding regions. Owing to their repeated structure, microsatellites are particularly prone to replication errors that are normally repaired by the Mismatch Repair (MMR) system. MMR is a very highly conserved cellular process, involving many proteins, resulting in the identification, and subsequent repair of mismatched bases, likely to have arisen during DNA replication, genetic recombination or chemical or physical damage. Proteins within the MMR system include MLH1, PMS2, MSH2, MSH6, MLH3, MSH3, PMS1, and Exo1. Deficient MMR (dMMR) results in a strong mutator phenotype known as microsatellite instability (MSI), characterized by widespread length polymorphisms of microsatellite sequences due to DNA polymerase slippage. MSI is recognized as one of the major carcinogenetic pathways of colorectal cancer (CRC): it represents a molecular hallmark of hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome (LS); moreover it is detected in 15% of sporadic colorectal cancers, more often due to an epigenetic inactivation of MLH1. Identification of MSI CRC is important, as MSI may serve as a screening tool for detecting LS, a prognostic marker for patient outcome, and a predictive marker for response to chemotherapy and to immunotherapy.
Helicobacter pylori (H. pylori) infection is one of the most common infection in humans, affecting more than half of the population. The prevalence of the infection varies widely in rural developing areas (more than 80%) compared to urban developed ones (less than 40%), as a consequence of different socioeconomic and hygienic conditions. H. pylori infection is usually acquired during childhood; infected people usually remain asymptomatic, but about 30% of individuals may develop mild to severe upper gastrointestinal diseases such as gastritis, peptic ulcer, gastric cancer or MALT lymphoma. The transmission route is not clear yet; the person-to-person transmission, especially within the same family appears to be prevalent, but also environmental contamination is possible. The eradication without a specific therapeutic regimen is very unlikely and the reinfection rate after an effective eradication therapy is quite rare. The reinfection rate will increase if there are family members affected.
Ulcerative colitis (UC) is associated with a substantial alteration of specific gut commensals, some of which may be involved in microbiota-mediated protection. In this study, microbiota cataloging of UC patients by 16S rRNA microbial profiling revealed a marked reduction of bifidobacteria, in particular the Bifidobacterium bifidum species, thus suggesting that this taxon plays a biological role in the aetiology of UC. We investigated this further through an in vivo trial by testing the effects of oral treatment with B. bifidum PRL2010 in a wild-type murine colitis model. TNBS-treated mice receiving 109 cells of B. bifidum PRL2010 showed a marked reduction of all colitis-associated histological indices as well as maintenance of mucosal integrity as it was shown by the increase in the expression of many tight junction-encoding genes. The protective role of B. bifidum PRL2010, as well as its sortase-dependent pili, appears to be established through the induction of an innate immune response of the host. These results highlight the importance of B. bifidum as a microbial biomarker for UC, revealing its role in protection against experimentally induced colitis.
1 January 2017 in World Journal of Gastroenterology
There are many causes of gastrointestinal bleeding (GIB) in children, and this condition is not rare, having a reported incidence of 6.4%. Causes vary with age, but show considerable overlap; moreover, while many of the causes in the pediatric population are similar to those in adults, some lesions are unique to children. The diagnostic approach for pediatric GIB includes definition of the etiology, localization of the bleeding site and determination of the severity of bleeding; timely and accurate diagnosis is necessary to reduce morbidity and mortality. To assist medical care providers in the evaluation and management of children with GIB, the “Gastro-Ped Bleed Team” of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) carried out a systematic search on MEDLINE via PubMed (http://www.ncbi.nlm.nih.gov/pubmed/ ) to identify all articles published in English from January 1990 to 2016; the following key words were used to conduct the electronic search: “upper GIB” and “pediatric” [all fields]; “lower GIB” and “pediatric” [all fields]; “obscure GIB” and “pediatric” [all fields]; “GIB” and “endoscopy” [all fields]; “GIB” and “therapy” [all fields]. The identified publications included articles describing randomized controlled trials, reviews, case reports, cohort studies, case-control studies and observational studies. References from the pertinent articles were also reviewed. This paper expresses a position statement of SIGENP that can have an immediate impact on clinical practice and for which sufficient evidence is not available in literature. The experts participating in this effort were selected according to their expertise and professional qualifications.
24 January 2018 in World Journal of Emergency Surgery
Iatrogenic colonoscopy perforation (ICP) is a severe complication that can occur during both diagnostic and therapeutic procedures. Although 45–60% of ICPs are diagnosed by the endoscopist while performing the colonoscopy, many ICPs are not immediately recognized but are instead suspected on the basis of clinical signs and symptoms that occur after the endoscopic procedure. There are three main therapeutic options for ICPs: endoscopic repair, conservative therapy, and surgery. The therapeutic approach must vary based on the setting of the diagnosis (intra- or post-colonoscopy), the type of ICP, the characteristics and general status of the patient, the operator’s level of experience, and surgical device availability. Although ICPs have been the focus of numerous publications, no guidelines have been created to standardize the management of ICPs. The aim of this article is to present the World Society of Emergency Surgery (WSES) guidelines for the management of ICP, which are intended to be used as a tool to promote global standards of care in case of ICP. These guidelines are not meant to substitute providers’ clinical judgment for individual patients, and they may need to be modified based on the medical team’s level of experience and the availability of local resources.