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Cold-snare endoscopic mucosal resection (CS-EMR) has been adapted in a piecemeal fashion as a safe and effective procedure for resection of colorectal polyps ≥10 mm. However, few data are available on en bloc CS-EMR for adenomas of 10 to 14 mm. Thus, this study evaluated the efficacy and safety of CS-EMR for these colorectal adenomas. In this single-arm, prospective, observational study, patients with at least 1 slightly elevated and sessile colorectal adenoma measuring 10 to 14 mm were recruited to undergo CS-EMR. The primary outcome was histological complete resection rate by CS-EMR, which was defined as en bloc resection, with a pathologically negative vertical margin and no neoplastic tissue obtained from 4 quadrants of the mucosal defect margin. Secondary outcomes were en bloc resection rate by CS-EMR, failure rate of CS-EMR, and the incidence of adverse events. A total of 80 polyps from 72 patients were included. CS-EMR failed in 11 lesions (13.7%), all of which were resected using a high-frequency electric current. The rates of en bloc resection and histologic complete resection by CS-EMR were 82.5% (66 of 80) and 63.8% (51 of 80), respectively. No bleeding occurred during the CS-EMR procedure, and there was no delayed bleeding or perforation at the site where CS-EMR was performed. CS-EMR can be safely performed in an en bloc fashion for some colorectal adenomas measuring 10 to 14 mm. However, there is room for improvement regarding the resectability and evaluation of the vertical margin after CS-EMR. (Clinical trial registration number: UMIN000031248.) [ABSTRACT FROM AUTHOR]

The optimal extent of lymph node dissection in patients receiving non-curative endoscopic submucosal dissection (ESD) and diagnosed with a positive vertical margin is unclear. This study attempted to identify optimal candidates for D2 lymph node dissection among these patients. This study included patients who underwent gastrectomy for primary gastric cancer following non-curative ESD with a positive vertical margin between January 2002 and December 2018. We classified the patients according to the positive vertical margin pattern into an obvious exposure group and a non-obvious exposure group. We developed a score model for predicting lymph node metastasis (LNM) using factors selected by multivariate analyses and beta regression coefficients, and the incidence of LNM was evaluated. This study included 110 patients. LNM was detected in 17 patients (15%). We developed a predictive scoring system as follows: tumor size >30 mm (0, No; 1, Yes) + undifferentiated type tumor in the invasive front (0, No; 2, Yes) + depth of submucosal invasion > 1500 μm (0, No; 1, Yes) + obvious tumor exposure at the vertical margin (0, No; 1, Yes). In patients with 5 points, the incidence rates of all and group 2 LNM were as high as 60% and 40%, respectively. Conversely, in patients with fewer than 5 points, the incidence rates of all and group 2 LNM were just 11% and 5%, respectively. In patients with 5 points according to our score model for predicting LNM, gastrectomy with D2 lymph node dissection is recommended. [ABSTRACT FROM AUTHOR]

Recent reports on gene expression profiling (GEP) show several genes associated with malignant progression of GIST. However, genes associated with malignant transformation have not been clarified. Here, we aimed to reveal distinct genes in aggressive malignant GIST, using comprehensive gene expression analysis. We investigated GEP obtained by microarrays for 43 gastric GISTs, which mostly harbored KIT and PDGFRA mutations and integrated clinicopathological risk information. RT-PCR and immunohistochemistry were performed for FZD7, a receptor of Wnt ligands. GEP divided 43 gastric GISTs into two clusters. A cluster included seven of eight high-risk GISTs (88%) in modified NIH classification and was defined as high-risk cluster; the other cluster was defined as low-risk cluster. The number of probes with over 3-fold changes between the two clusters was 1,177, in which probes corresponding to 16 oncogenes were included. Genes involved in the Wnt signaling pathway were the most abundant among the 16 oncogenes. Focusing on 73 Wnt signaling pathway genes of the 21,578 probes, 12 upregulated and 5 downregulated genes were found in the high-risk cluster. Major cascade genes promoting the Wnt/β-catenin signaling pathway, including WNT11 , FZD family, and DVL2, were upregulated in the high-risk cluster. SNAI1 , SNAI2, and BIRC5 , which are activated by this pathway and increase cell proliferation, were also upregulated. These gene expression alterations were consistent in the positive direction of this pathway. GISTs in high-risk cluster strongly expressed FZD7. Wnt/β-catenin signaling pathway may play an important role in malignant transformation of indolent GIST. - Low and high clinical risk clusters were separated by gene expression profiling - The Wnt/β-catenin signaling pathway was activated in aggressive malignant GIST - Malignant GIST strongly expressed FZD7, a receptor of Wnt ligands [ABSTRACT FROM AUTHOR]

Gastric neuroendocrine carcinoma (G-NEC) usually has NEC and adenocarcinoma components and is considered to have a common origin in gastric adenocarcinoma because common pathogenic mutations are shared. However, G-NEC without adenocarcinoma also exists, and it may have a different mechanism of tumorigenesis. We aimed to elucidate the tumorigenesis of G-NEC by focusing on the proportion of NEC components. Thirteen patients with G-NEC were included in this study. Comprehensive genetic analysis using whole-exome sequencing was performed. G-NEC without an adenocarcinoma component was defined as pure NEC. TP53 was detected as the most frequent gene mutation (85% of the patients), independent of classification. RB1 , KMT2C , LTBP1 , and RYR2 mutations were identified in two of three pure NEC patients but were not detected in other G-NEC patients. Pure NEC has different somatic mutation profile than other NECs. This study provides insights into the mechanism of tumorigenesis in G-NEC. [ABSTRACT FROM AUTHOR]