Circulating plasma microRNAs in colorectal neoplasia: A pilot study in assessing response to therapy.

INTRODUCTION: Current serological surveillance markers to monitor colorectal cancer (CRC) or colorectal advanced adenomas (CAA) are hampered by poor sensitivity and specificity. The aim of this study is to identify and validate a panel of plasma microRNAs which change in expression after resection of such lesions. METHODS: A prospectively maintained colorectal surgery database was queried for patients in whom both pre- and post-procedural serum samples had been obtained. An initial screening analysis of CRC and CAA patients (5 each) was conducted using screening cards for 380 miRNAs. Four identified miRNAs were combined with a previously described panel of 7 miRNAs that were diagnostically predictive of CRC and CAA. Differential miRNA expression was assessed using quantitative real-time polymerase chain reaction(qRT-PCR). RESULTS: Fifty patients were included (n = 27 CRC, n = 23 CAA). There was no difference in age, gender, or race profile of CRC patients compared to CAA patients. Six miRNA were significantly increased after CRC resection (miR-324, let7b, miR-454, miR-374a, miR-122, miR-19b, all p<0.05), while three miRNAs were significantly increased following CAA resection (miR-454, miR-374a, miR-122, all p<0.05). Three miRNA were increased in common for both (miR-454, miR-374a, miR-122). DISCUSSION: The expression of miRNAs associated with neoplasia (either CRC or CAA) was significantly increased following surgical resection or endoscopic removal of CRC or CAA. Future studies should focus on the evaluation of these miRNAs in CRC and CAA prognosis.

Pyoderma Gangrenosum in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Pyoderma gangrenosum (PG) is an uncommon but severe extra-intestinal manifestation (EIM) of inflammatory bowel disease (IBD). The incidence and risk factors for PG are disputed. AIMS: To assess the incidence of PG and identify factors associated with PG in IBD patients. METHODS: A search of electronic databases (Ovid and PubMed) was conducted between 1966 and 2019. Studies that calculated the incidence of PG in IBD patient cohorts were included. Patient demographics, IBD subtype, and EIM presence were recorded. A review of our institutional database of 1057 IBD patients was conducted. A multivariate regression model and meta-analysis were conducted to identify risk factors for PG. A random effects model was used to combine the data of included studies. RESULTS: Fourteen studies were included in addition to 1057 IBD patients and 26 PG cases from the Louisville cohort. In total, there were 379 cases of PG in the cumulative cohort of 61,695 IBD patients. The PG incidence in individual studies ranged from 0.4 to 2.6%. In the institutional cohort, ocular EIMs and a permanent stoma were significant risk factors for PG. In the meta-analysis, PG was associated with female gender (RR = 1.328, 95% CI 1.161-1.520), Crohn's disease (RR = 1.193, 95% CI 1.001-1.422), erythema nodosum (RR = 9.281, 95% CI 6.081-14.164), and ocular EIM (RR = 4.55, 95% CI 3.04-6.81). There was study heterogeneity when assessing IBD subtype, ocular, and joint EIMs. CONCLUSIONS: There are conflicting data on the incidence and risk factors for PG. This meta-analysis confirms an association between PG and female gender, Crohn's disease, erythema nodosum, and ocular EIM that have been described in smaller studies.

Plasma microRNA Profile Differentiates Crohn's Colitis From Ulcerative Colitis.

Background: Inflammatory bowel disease (IBD) is commonly divided into 2 entities: Crohn's disease (CD) and ulcerative colitis (UC). Differentiating between these entities when dealing with IBD confined to the colon is important, especially when planning surgical treatment. Due to ambiguous histological or endoscopic findings, accurate diagnosis is not possible in up to 15% of cases. The aim of this study was to determine whether plasma microRNAs (miRNAs) can help differentiate Crohn's colitis (CC) from ulcerative colitis. Methods: Patients with isolated CC and with UC were enrolled in our study from January 2010 to May 2016. Peripheral blood was collected, and total RNA was isolated from plasma. Screening was performed for 380 common miRNAs. miRNAs that were differentially expressed between these 2 groups were chosen, and their differential expression was confirmed using single miRNA assays in a larger sample size. A predictive model was generated using these data. Significantly differentially expressed miRNAs were then validated utilizing the predictive model to assess blinded data from the single assays. Results: Screening was performed on 8 patients from each group. Seven differentially expressed miRNAs were chosen for single assay confirmation. Two miRNAs (miR-598, miR-642) were consistently different between the patient groups (P = 0.013, P = 0.005). Using blinded data, these 2 miRNAs were validated using the predictive model, achieving an overall accuracy of 75% (95% confidence interval, 40.7-92.9). Conclusions: We identified 2 plasma miRNAs that differentiated CC from UC. Our data indicate the promise and feasibility of a plasma miRNA-based assay to distinguish between these 2 conditions.