Association of microRNA-31 with BRAF mutation, colorectal cancer survival and serrated pathway.

BRAF is an important gene in colorectal cancers (CRCs) that is associated with molecular characterization and resistance to targeted therapy. Although microRNAs (miRNAs) are useful biomarkers of various cancers, the association between miRNA and BRAF in CRCs is undefined. Therefore, this study was conducted to identify a relationship between specific miRNA molecules and BRAF mutation in CRCs and serrated lesions. miRNA array was used for the measurement of 760 miRNAs in 29 CRCs. To assess the identified miRNAs, quantitative reverse transcription-PCR was performed on 721 CRCs, 381 serrated lesions and 251 non-serrated adenomas. Moreover, proliferation and invasion assays were conducted using cell lines. miRNA array analysis revealed that microRNA-31 (miR-31)-5p was the most up-regulated miRNA in CRCs with mutated BRAF (V600E) compared with CRCs possessing wild-type BRAF (including cases with KRAS mutation). High miR-31 expression was associated with BRAF and KRAS mutations and proximal location (P < 0.0001). High miR-31 expression was related to cancer-specific mortality [multivariate hazard ratio = 2.06, 95% confidence interval: 1.36-3.09, P = 0.0008]. Functional analysis demonstrated that miR-31 inhibitor decreased cell invasion and proliferation. With regard to serrated lesions, high miR-31 expression was less frequently detected in hyperplastic polyps compared with other serrated lesions. In conclusion, associations were identified between miR-31, BRAF and prognosis in CRC. Transfection of miR-31 inhibitor had an antitumour effect. Thus, miR-31 may be a promising diagnostic biomarker and therapeutic target in colon cancers. Moreover, high miR-31 expression in serrated lesions suggested that miR-31 may be a key molecule in serrated pathway.

Use of capsule endoscopy in patients with Crohn's disease in Japan: a multicenter survey.

BACKGROUND AND AIM: Until the approval of patency capsule, capsule endoscopy (CE) has not been routinely applied for the diagnosis of Crohn's disease (CD) in Japan. We aimed to survey current situation of CE use for patients with CD in Japan. METHODS: The nationwide survey of 40 Japanese institutions identified 94 patients with established CD (eCD) and 80 patients with suspected CD (sCD), who were examined by CE. Types and positive rates of mucosal injury under CE and capsule retention rate were investigated. In sCD, final diagnosis after CE was also analyzed. RESULTS: Patients with eCD comprised 82 patients of ileitis or ileocolitis type, while 12 patients had CD of colitis type. CE identified mucosal injuries in 83 of 94 patients. Eight of 12 patients with eCD of colitis type had ileal lesions under CE, thereby being reclassified as ileocolitis type. In patients with sCD, CE detected mucosal injuries in 58 patients. Linear ulceration and cobblestone appearance were depicted in 22 and 3 patients, respectively, thereby resulting in established diagnosis of CD in 23 patients. Mucosal lesion was not found in 22 patients with sCD, who were diagnosed as not having CD. Capsule retention rate was not statistically different between patients with eCD and those with sCD (7.4% vs 6.3%, P = 1.0). CONCLUSIONS: CE is useful for the evaluation of small bowel mucosal injuries in Japanese patients with sCD and eCD. Possible intestinal stricture needs to be carefully evaluated before CE even in patients with sCD.

Inferior mesenteric venous thrombosis that required operations: report of two cases.

Inferior mesenteric venous thrombosis (IMVT) is a very rare disease of colon ischemia. We experienced two cases of IMVT that required operations. The first patient was a 74-year-old male, who was admitted to our hospital because of melena and diarrhea. He was diagnosed with IMVT by angiography. As no improvement was seen after the conservative therapy for a month, left colectomy and transverse colostomy were performed. There was a small ulcer in the resected colon mucosa. The findings of histopathological examination revealed that mild and repeated ischemia of the colon had been caused. The second patient was a 70-year-old male, who was admitted to our hospital with the chief complaint of constipation, lower abdominal pain and nausea. He was diagnosed as IMVT by angiography. As no improvement was seen after the conservative therapy for a month, an operation was performed. The operative findings confirmed severe swelling of mesenteric fatty tissue and vascular ectasia of mesocolon. Left colectomy and transverse colostomy were performed. Histopathological examination of surgical specimens disclosed the multiple thrombi and almost complete occlusion of the inferior mesenteric vein, the invasion of lipid-filled macrophages as mesenteric panniculitis, and ischemic change in the sigmoid colon mucosa.

[Case of ulcerative colitis refractory to intravenous cyclosporine therapy successfully treated with infliximab].

A 26-year-old woman was admitted to our hospital with relapse of ulcerative colitis (UC). We diagnosed it as a refractory UC because intravenous corticosteroid therapy had no effect. Intravenous cyclosporine therapy and other conventional therapies did not lead to remission. Then the possibility of infliximab was discussed with the patient and her parents and treatment with infliximab was started. Infliximab was infused intravenously at a dose of 5mg per kilograms of body weight. Immediately after the first infusion, clinical symptoms improved, and clinical remission was achieved within 12 weeks. It is suggested that infliximab can be effective for refractory UC.

A randomized, double-blinded, placebo-controlled, multicenter trial, healing effect of rebamipide in patients with low-dose aspirin and/or non-steroidal anti-inflammatory drug induced small bowel injury.

BACKGROUND: It is not clear what kind of drug is appropriate to heal NSAID-induced enteropathy. Several reports showed the preventive effect of prostaglandin analogue or inducer using healthy subjects who took NSAIDs. However there was no report for healing effect and for patients. The aim of this study was to evaluate the healing effect of rebamipide in patients with NSAIDs-induced enteropathy. In addition, we evaluated for nutritional parameter. METHODS: This study was conducted as a randomized, double-blinded, placebo-controlled, multicenter trial. Study protocol was approved by each hospital's ethical committees. Patients with LDA and/or NSAID more than 3 months were enrolled. Patients with enteropathy were divided into the placebo and the rebamipide groups. Rebamipide 100 mg three times daily was administered during 4 weeks. Capsule endoscopies were performed at 0 and 4 week. The number of small intestinal ulcer and erosion were evaluated. Total protein was analyzed as nutritional parameter. RESULTS: Sixty one participants were completed this study. Change in number of small intestinal erosion in the rebamipide group was -2.5 ± 3.4, and 2.1 ± 3.9 in the placebo group (P < 0.0001). Change in number of small intestinal ulcer in the rebamipide group was -0.5 ± 1.6, and 0.1 ± 0.7 in the placebo group (P = 0.024). Change in serum total protein levels in the rebamipide group was 0.06 ± 0.36, and -0.27 ± 0.34 in the placebo group (P = 0.0005). CONCLUSIONS: Rebamipide has not only the healing effect for NSAIDs-induced enteropathy compared with placebo, but the improvement of nutritional condition. These results showed a tentative therapeutical strategy for chronic NSAIDs users.