The IBD-associated long noncoding RNA IFNG-AS1 regulates the balance between inflammatory and anti-inflammatory cytokine production after T-cell stimulation.

The inflammatory bowel diseases (IBD) are a complex set of chronic gastrointestinal inflammatory conditions arising from the interplay of genetic and environmental factors. This study focuses on noncoding RNA transcripts as potential mediators of IBD pathophysiology. One particular gene, interferon γ-antisense 1 (IFNG-AS1), has been consistently observed to be elevated in the intestinal mucosa of patients with actively inflamed IBD versus healthy controls. This study builds on these observations, demonstrating that the second splice variant is specifically altered, and this alteration even stratifies within inflamed patients. With the use of a CRISPR-based overexpression system, IFNG-AS1 was selectively overexpressed directly from its genomic loci in T cells. An unbiased mRNA array on these cells identified a large increase in many inflammatory cytokines and a decrease in anti-inflammatory cytokines after IFNG-AS1 overexpression. Media from T cells overexpressing IFNG-AS1 elicited an inflammatory signaling cascade in primary human peripheral blood mononuclear cells, suggesting the potential functional importance of IFNG-AS1 in IBD pathophysiology. The significance of these results is amplified by studies suggesting that a single-nucleotide polymorphism in IFNG-AS1, rs7134599, was associated with both subtypes of patients with IBD independently of race.NEW & NOTEWORTHY Long noncoding RNAs are an emerging field of inflammatory bowel disease (IBD) research. This study mechanistically analyzes the role of a commonly upregulated gene in IBD and shows IFNG-AS1 as a mediator of an inflammatory signaling cascade.

The Utility of EUS-FNA to Determine Surgical Candidacy in Patients with Pancreatic Cancer after Neoadjuvant Therapy.

BACKGROUND: In patients with borderline resectable pancreatic cancer (BRPC) or locally advanced pancreatic cancer (LAPC) who undergo neoadjuvant therapy, CT imaging is the standard of care for restaging. However, differentiating residual tumor from post-treatment inflammation with CT is unreliable. The diagnosis of periarterial soft tissue cuffing (PSTC) near major vessels is key to guiding resectability. The goal of this study was to assess the utility of EUS-FNA in determining the etiology of PSTC in BRPC or LAPC after neoadjuvant treatment. METHODS: We performed a retrospective analysis of patients referred for EUS-FNA of PSTC following downstaging therapy for LAPC or BRPC at our tertiary medical center. Negative EUS-FNA cytology results were compared with surgical pathology after resection. Patients with positive EUS-FNA cytology results were either followed clinically or results were compared to surgical pathology if surgery was attempted despite the positive cytology. RESULTS: Fourteen patients were included in the study of whom four had positive cytology. Two of these patients had progression of disease, and two had attempted resection with positive surgical pathology (100% true positives). All ten patients with negative cytology underwent attempted surgical resection. Nine patients (90%) achieved negative margins, and one patient (10%) had a positive surgical margin. The sensitivity, specificity, and accuracy of EUS-FNA for determining resectability were 80%, 100%, and 92.9%, respectively. CONCLUSIONS: In this series of patients with BRPC or LAPC and persistent PSTC after downstaging neoadjuvant treatment, EUS-FNA accurately determined surgical resectability and should be considered as part of the evaluation of such patients.