中川 義仁

Small bowel tumors (SBTs) are uncommon, insidious in presentation, and frequently represent a diagnostic challenge. The advent of video capsule endoscopy (VCE) and double-balloon endoscopy (DBE) is a significant breakthrough for visual diagnosis of SBTs throughout the small bowel. Contrast-enhanced computed tomography (CECT) and fluoroscopic enteroclysis had significantly lower diagnostic yields of tumors that were 10 mm or smaller in diameter, but VCE and DBE had high diagnostic yields regardless of tumor size. Regarding SBTs larger than 10 mm in diameter, CECT had a significantly lower diagnostic yield of epithelial tumors compared to subepithelial tumors, whereas fluoroscopic enteroclysis and DBE had high diagnostic yields regardless of the tumor type. VCE had a slightly lower diagnostic yield of subepithelial tumors (78%) compared to epithelial tumors. Therefore, a combined examination method by using CECT and VCE is useful for screening of SBTs. In case suspicious of stenosis, patency capsule should be performed to confirm passage before VCE. DBE is useful for further precise examination including biopsy and ultrasonography by using miniature probe, and enteroscopic treatment. After medical, enteroscopic, and surgical treatment, VCE is helpful for follow-up. DBE is safe and useful in resecting the SBTs deep within the small bowel without laparotomy. Indications of enteroscopic resection may be benign tumors regardless of epithelial or subepithelial type, localizing in the mucosal or submucosal layer, which are symptomatic at present or possibly symptomatic or transforming in the future. Malignant tumors localized in the mucosal layer may be indications although detecting at an early stage is challenging. In this review article, we describe management of SBTs/polyps by various modalities.

Accumulating data indicate that some microRNAs (miRNAs or miRs) can function as tumor suppressors or oncogenes and as such are important in cancer development. We previously reported that miR-143 and -145 are frequently downregulated in colon adenomas and cancers, acting as tumor suppressors. In this present study, we investigated the relationship between the downregulation of the miR-143/145 cluster and genetic aberrations of adenomatous polyposis coli (APC), which are early genetic events in the development of colorectal tumors. The expression levels of both miRs were determined by performing real-time PCR on tissue samples of familial adenomatous polyposis (FAP), colorectal adenoma, colorectal cancer, and paired non-tumorous tissues. Also, the expression of C- or N-terminus of the APC protein and that of the p53 protein in these tissues were examined immunohistochemically. Our data clearly indicated that the decreased expression of miR-143 and -145 frequently occurred before APC gene aberrations. The downregulation of miR-143 and -145 is thus an important genetic event for the initiation step in colorectal tumor development. © 2013 The Japanese Society for Clinical Molecular Morphology.

Common single-nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) have been shown to be associated with susceptibility to several types of human cancer. We evaluated the association between three SNPs (rs11614913, rs2910164 and rs3746444) in pre-miRNAs (miR-196a2, miR-146a and miR-499) and various clinicopathological characteristics, including CpG island hypermethylation (CIHM) status and overall survival in gastric cancer (GC) patients. rs11614913 (T>C), rs2910164 (C>G) and rs3746444 (A>G) SNPs were genotyped in 127 GC patients. OHM of p14, p16, DAP-kinase and CDH1 genes was determined by methylation-specific polymerase chain reaction in the cancer tissues. A significant marginal association was found between the rs11614913 CC genotype and polypoid or elevated type morphology in early-stage GC (OR=6.29, 95% CI 1.18-33.47, p=0.03). The rs2910164 CC and CG genotypes were associated with increased susceptibility to CIHM of DAP-kinase OR=5.48, 95% CI 1.30-23.10, p=0.02; CC, OR=6.93, 95% Cl 1.37-35.02, p=0.02; OD, OR=4.24, 95% CI 0.87-20.78, p=0.07). The 11614913 TT and TC genotypes were associated with a higher number of CIHM (no. of CIHM 0-1 vs. 2-4; TT+TC, OR=3.67, 95% CI 0.98-13.72, p=0.05; TC, OR=4.08, 95% CI 1.04-15.97, p=0.04). When the subjects were divided according to age group, the combined rs11614913 TT+TC genotype tended to be associated with worse overall survival than the CC genotype in patients younger than 65 years of age (p=0.05). The combined rs2910164 CG+GG genotype also tended to be associated with worse overall survival than the CC genotype in the same age group (p=0.09). It appears that rs11614913 and rs2910164 SNPs in pre-miRNAs (miR-196a2 and miR-146a) affect the clinicopathological characteristics of GC, including its morphological appearance. CIHM status and overall survival.