Background and study aims: Although endoscopic submucosal dissection (ESD) is an established therapy for colon neoplasms including laterally spreading tumors (LSTs), its application to advanced fibrotic lesions is very difficult owing to the thin walls of the large intestine. We examined the ability of preoperative endoscopic ultrasonography (EUS) to predict lesion fibrosis in patients undergoing colorectal ESD. Patients and methods: From 2009 to 2013, 58 LSTs were evaluated retrospectively with EUS and treated using colorectal ESD. The degree of submucosal fibrosis was determined during ESD and classified as F0 (no fibrosis), F1 (mild fibrosis), or F2 (severe fibrosis). Results: The sensitivity and specificity of fibrosis prediction by preoperative EUS of all cases were 77.8 % and 57.1 %, respectively. However, there was a high accuracy (97.2 %, 35/36) for only the 36 LSTs with clear and visible images. In one case, EUS diagnosed no fibrosis but significant fibrosis was found during ESD, the result of colon cancer invasion into the submucosa. Conclusions: Preoperative EUS before colorectal ESD successfully predicted the degree of fibrosis in a number of cases.

Human neutrophil peptides (HNPs) are antimicrobial peptides produced predominantly by neutrophils. We have previously reported that HNP 1-3 levels are increased in the sera and plasma of patients with active ulcerative colitis. The increased expression of interleukin-8 (IL-8) has also been demonstrated in the colonic mucosa of patients with active ulcerative colitis. HNPs induce IL-8 in lung epithelial cells and monocytes through the P2Y6 signaling pathway. However, the association between HNPs and IL-8 in the intestinal mucosa has not yet been investigated. In the present study, we investigated the effects of HNP-1 on the production of IL-8 by human intestinal epithelial cells and the underlying signaling mechanisms. We observed a significant increase in IL-8 expression in the human colon carcinoma cell line, Caco-2, following treatment with HNP-1. The non-selective P2 receptor antagonists, suramin and pyridoxal phosphate-6-azo (benzene-2,4-disulfonic acid) tetrasodium salt hydrate (PPADS), significantly blocked the HNP-1-induced expression of IL-8 in the Caco-2 cells. The P2Y6-specific antagonist, MRS2578, led to a significant but partial decrease in IL-8 expression, suggesting that P2 receptors in addition to P2Y6 are involved in the HNP-1-induced production of IL-8 by Caco-2 cells. In agreement with this finding, HNP-1 also significantly increased IL-8 production in the P2Y6-negative human colon cancer cell line, HT-29, and this increase was blocked by treatment with suramin and PPADS. HNP-1 significantly increased the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) in the HT-29 cells. However, the HNP-1-induced production of IL-8 was suppressed by the ERK1/2 inhibitor, U0126, but not by the p38 MAPK inhibitor, SB203580. In conclusion, our data demonstrate that HNP-1 induces IL-8 production not only through P2Y6, but also through additional P2 receptors via an ERK1/2-dependent mechanism in intestinal epithelial cells.

Dysbiosis of the enteric microbiota causes gastrointestinal diseases, including colitis. The present study investigated the beneficial effect of Lactobacillus plantarum 06CC2 in experimental colitis in mice. An experimental colitis model in C57BL6 mice was induced using dextran sulfate sodium. Mice were orally administered 06CC2 (06CC2 group) or PBS only (control group) by gavage. The disease activity index (DAI), histological grading, and colon tissue and colonic lamina propria mononuclear cells (LPMCs) were examined macroscopically and histopathologically, and the expression levels of inflammation‑associated cytokines (IL‑6, IL‑12, TNF‑α and IL‑10) in these samples were determined. Compared with the control group, the 06CC2 group exhibited a significantly lower DAI (1.5±0.8 vs. 0.2±0.3, respectively; P<0.05) and pathology score (6.3±1.5 vs. 3.8±1.3, respectively; P<0.05). IL‑10 expression in colonic LPMCs was higher in the 06CC2 group than in the control group, although there was no significant difference in IFN‑γ, IL‑6 or IL‑12 expression in colonic LPMCs between the two groups. In addition, 06CC2 stimulated the production of IL‑10 from CD11b‑positive cells and CD11c‑positive cells in the colon. The 06CC2 strain induced IL‑10 production in the colon and attenuated colon inflammation.

Background/Aims: Esophageal mucosal damage often causes scar tissue, leading to refractory stricture. The aim of this study was to clarify the effect of hepatocyte growth factor (HGF) on esophageal mucosal repair and fibrosis leading to stricture in a rat model of esophageal ulcer. Methods: Esophageal ulcers were induced in rats by topical exposure of the lower esophageal serosa to acetic acid, followed by intraperitoneal administration of HGF (200 µg/day) using an osmotic pump for 7 days. The effect of HGF on esophageal mucosal injury was investigated macroscopically and microscopically. The effect of HGF on epithelial cell proliferation and the expression of genes closely associated with the development of fibrosis were also examined. Results: The administration of HGF for 7 days led to a significant reduction in the ulcerative area and enhanced the proliferation of esophageal epithelial cells. HGF treatment significantly decreased the fibrosis, and subsequently attenuated not only the foreshortening but also the narrowing of the esophagus. The expression levels of tissue inhibitor of metalloproteinase (TIMP)-1, -2, and matrix metalloproteinase (MMP)-2, -9 were significantly decreased among rats treated with HGF. Conclusion: HGF facilitates the repair of esophageal mucosal injury and may also ameliorate the esophageal fibrosis, possibly through enhanced re-epithelization.

This study evaluated the feasibility and clinical utility of liquid-based cytology (LBC) specimens via endoscopic ultrasound–guided fine-needle biopsy (EUS-FNB) for next-generation sequencing (NGS) of pancreatic cancer (PC). We prospectively evaluated the performance of DNA extraction and NGS using EUS-FNB samples obtained from PC. Thirty-three consecutive patients with PC who underwent EUS-FNB at our hospital were enrolled. DNA samples were obtained from 96.8% of the patients. When stratified with a variant allele frequency (VAF) > 10% tumor burden, the NGS success rate was 76.7% (n = 23) in formalin-fixed paraffin-embedded (FFPE), 83.3% (n = 25) in LBC, and 76.7% (n = 23) in frozen samples. The overall NGS success rate was 86.7% (n = 26) using FFPE, LBC, or frozen samples. The detection rates for the main mutated genes were as follows: 86.7% for KRAS, 73.3% for TP53, 66.7% for CDKN2A, 36.7% for SMAD4, and 16.7% for ARID1A. LBC had the highest median value of VAF (23.5%) for KRAS and TP53. PC mutation analysis using NGS was successfully performed using LBC compared with FFPE and frozen samples. This approach provides an alternative and affordable source of molecular testing materials.