Covering the Cover

Two nationwide studies examine endoscopist performance and colorectal cancer after colonoscopy. Surveillance screening colonoscopy is based on characteristics of removed adenomas but not the endoscopists. In this issue Gastroenterology, Wieszczy et al examined endoscopists (CRC) risk in a Polish cohort. A total 173,288 colonoscopies were performed between 2000 2011 followed up until 2017. Of 262 endoscopists, 160 (61%) classified as low performers with adenoma detection rate <20%, whereas 102 (39%) high >20%. 443 CRCs diagnosed during 10 years follow-up. The incidence CRC among individuals negative 0.30% versus 0.15% (hazard ratio, 2.10; 95% confidence interval, 1.52–2.91) when done by performers. Similarly, incidences 0.55% 0.22% 2.35; 1.31–4.21) low-risk adenoma, 1.14% 0.43% 2.69; 1.62–4.47) high-risk adenomas. Similar trends observed an Austrian These results suggest that can be important contributor determining See page 1067. randomized study compared different strategies uptake. Screening uptake rates remain suboptimal despite universal recommendations for eligible individuals. Pilonis 3 offering population-wide multicenter trial. 12,452 randomly assigned to 1 strategies: invitation only (control), fecal immunochemical test testing nonresponders (sequential), choice or (choice). participation control group (17.5%) was lower than sequential (25.8%) (26.5%) strategies. participants positive 70.0% 73.3% group. Advanced neoplasia comparable groups (1.1% vs 1.0% 1.1%) intention-to-screen analysis. This shows while strategy increased program rates, they did improve advanced (Figure 1). 1097. Colorectal transcriptome analysis confirms multiple susceptibility loci identifies new molecular targets. Advances sequencing technology computational approaches have generated large genomic datasets provide invaluable insight into many cancers' underpinnings. Yet, cases, underlying genetic mechanisms mostly unknown. Guo Lin perform sizeable transcriptome-wide association identify novel genes. Gene expression prediction models developed from genotype-tissue data validated Cancer Genome Atlas data. then used assess associations predicted gene roughly 58,000 67,000 identifying several previously discovered well 4 2). They identified CABLES2 candidate associated lead single nucleotide polymorphism. Functional determined allele decreased promoter activity. knockdown SW480 cells resulted viability, migration, invasion, vivo xenograft growth. Transcriptomic indicated loss promotes PI3K-AKT signaling. sum, confirmed implicated genes, additional functionally characterized one such gene—CABLES2. work warrants functional characterization other variants 1164. Differential roles cancer-associated fibroblast production GREM1 ISLR result opposite bone morphogenetic protein signaling metastasis impacts. Significant research efforts devoted understanding alterations prime promote malignant degeneration yielded essential insights led cancer-directed therapeutics. However, we know progression involves partnership tumor microenvironment. Cancer-associated fibroblasts (CAFs) both inhibit survival through host activities, including secreted growth factors proteins (BMPs). Kobayashi use transcriptomic CAF-specific regulators BMP Both stroma; however, survival, improved survival. mouse colon, noted co-express ISLR. Grem1+ present at crypt base, Islr+ localized middle crypt. Furthermore, Grem1 coincided Foxl1+ telocytes. addition, Foxl1 overexpression induced suppressed Isrl transcription. Employing inflammatory carcinogenesis modeling, Islr independently expressed CAF populations. Treating organoids either GREM1-neutralizing antibody conditioned media ISLR-overexpressing signaling, promoted differentiation, reduced organoid Finally, slightly hepatic tumoroid model, tail vein injection AAV-Islr significantly metastatic burden. experiments collectively demonstrate induce stromal respectively, differential these key CAFs produce protumorigenic conditions. 1224.