BACKGROUND/AIMS: Diverticular bleeding can occasionally cause massive bleeding that requires urgent colonoscopy (CS) and treatment. The aim of this study was to identify significant risk factors for colonic diverticular hemorrhage. METHODS: Between January 2009 and December 2012, 26,602 patients underwent CS at our institution. One hundred twenty-three patients underwent an urgent CS due to acute lower gastrointestinal hemorrhage. Seventy-two patients were diagnosed with colonic diverticular hemorrhage. One hundred forty-nine age- and sex-matched controls were selected from the patients with nonbleeding diverticula who underwent CS during the same period. The relationship of risk factors to diverticular bleeding was compared between the cases and controls. RESULTS: Uni- and multivariate conditional logistic regression analyses demonstrated that the use of nonsteroidal anti-inflammatory drugs (odds ratio [OR], 14.70; 95% confidence interval [CI], 3.89 to 55.80; p<0.0001), as well as the presence of cerebrovascular disease (OR, 8.66; 95% CI, 2.33 to 32.10; p=0.00126), and hyperuricemia (OR, 15.5; 95% CI, 1.74 to 138.00; p=0.014) remained statistically significant predictors of diverticular bleeding. CONCLUSIONS: Nonsteroidal anti-inflammatory drugs, cerebrovascular disease and hyperuricemia were significant risks for colonic diverticular hemorrhage. The knowledge obtained from this study may provide some insight into the diagnostic process for patients with lower gastrointestinal bleeding.
Adult ; Aged ; Aged, 80 and over ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects ; Case-Control Studies ; Cerebrovascular Disorders/complications ; Colonic Diseases/*etiology/surgery ; Colonoscopy ; Diverticulum, Colon/*complications/pathology/surgery ; Female ; Gastrointestinal Hemorrhage/*etiology/surgery ; Humans ; Hyperuricemia/complications ; Logistic Models ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors

Quercetin, a flavonoid, widely distributed in many fruits and vegetables, is well known to have an anti-tumor effect despite its mutagenicity. In this study, we examined the effect of dietary quercetin on duodenum-tumorigenicity of mice induced by a chemical carcinogen, N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG). Eight-week-old male C57BL/6 mice were divided into 4 groups; ENNG without quercetin (group A), ENNG with 0.2% quercetin (group B), ENNG with 2% quercetin (group C), and 2% quercetin without ENNG (group D). ENNG was given in drinking water for the first 4 weeks, and thereafter quercetin was given in a mixed diet. At week 20, the average number of duodenal tumors per mouse was significantly higher in group C (mean±SE, 7.26±1.75, p<0.05) than in group A (2.32±0.31). The size of the duodenal tumors increased significantly in group B (1.79±0.09 mm, p<0.001) compared with group A (1.43±0.09 mm). In contrast, no duodenal tumor was induced in group D. The present findings suggest that excessive intake of quercetin occasionally is a risk factor for carcinogenesis of some specific organs such as the upper intestine.
Quercetin ; Upper Case En ; ENNG ; week ; Laboratory mice

Quercetin, a flavonoid, widely distributed in many fruits and vegetables, is well known to have an antitumor effect despite its mutagenicity. In this study, we examined the effect of dietary quercetin on duodenum-tumorigenicity of mice induced by a chemical carcinogen, N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG). Eight-week-old male C57BL/6 mice were divided into 4 groups; ENNG without quercetin (group A), ENNG with 0.2% quercetin (group B), ENNG with 2% quercetin (group C), and 2% quercetin without ENNG (group D). ENNG was given in drinking water for the first 4 weeks, and thereafter quercetin was given in a mixed diet. At week 20, the average number of duodenal tumors per mouse was significantly higher in group C (mean±SE, 7.26±1.75, p<0.05) than in group A (2.32±0.31). The size of the duodenal tumors increased significantly in group B (1.79±0.09 mm, p<0.001) compared with group A (1.43±0.09 mm). In contrast, no duodenal tumor was induced in group D. The present findings suggest that excessive intake of quercetin occasionally is a risk factor for carcinogenesis of some specific organs such as the upper intestine.

BACKGROUND/AIMS: Both fecal immunochemical test (FIT) and fecal calprotectin (Fcal) results are useful biomarkers for ulcerative colitis (UC). However, the situations in which each marker should be used are largely unknown. METHODS: A total of 110 colonoscopy intervals of UC patients were assessed, and correlations between changes in colonoscopic findings and changes in the two aforementioned fecal markers were examined. RESULTS: Among patients with mucosal healing (MH) and negative FIT or Fcal results at the initial colonoscopy, FIT and Fcal findings exhibited accuracies of 93% (38/41) and 79% (26/33), respectively, for predicting the results of the subsequent examination. Among the 24 patients who showed endoscopic activity at the precedent colonoscopy and MH at the subsequent examination, positive-to-negative conversion of FIT and Fcal findings at the subsequent examination was observed in 92% (12/13) and 62% (8/13) of patients, respectively. Among the 43 patients who showed endoscopic activity at both the precedent and subsequent examinations, Fcal findings reflected the change in endoscopic activity better than FIT results (r=0.59, p<0.0001 vs r=0.30, p=0.054). CONCLUSIONS: The FIT is useful for confirming MH and the occurrence of relapse. In contrast, Fcal is useful for monitoring the mucosal status of patients with active inflammation.
Biomarkers ; Colitis ; Colitis, Ulcerative* ; Colonoscopy ; Humans ; Inflammation ; Leukocyte L1 Antigen Complex* ; Recurrence ; Ulcer*

BACKGROUND/AIMS: Although mucosal healing (MH) has been considered a treatment goal for patients with ulcerative colitis (UC), the risk factors predictive of relapse in patients who achieve MH are unknown. Because the platelet count has been shown to be a marker of inflammation in inflammatory bowel diseases, this study aimed to assess whether the platelet count could predict relapse in UC patients with MH. METHODS: A prospective observational study was performed. UC patients with MH were consecutively enrolled in the study and monitored for at least 2 years or until relapse. The correlation between the incidence of relapse and the platelet count at the time of study enrollment was examined. RESULTS: In total, 43 patients were enrolled, and 14 patients (33%) relapsed. The median platelet count at the time of enrollment in the patients who relapsed significantly differed from that in the patients who did not relapse (27.2×104/μL vs 23.8×104/μL, respectively; p=0.016). A platelet count >25.0×104/μL was a significant risk factor for relapse based on a multivariate analysis (hazard ratio, 4.85; 95% confidence interval, 1.07 to 25.28), and according to the Kaplan-Meier analysis, this cutoff could identify patients susceptible to relapse (p=0.041, log-rank test). CONCLUSIONS: The platelet count could be used as a predictor of relapse in UC patients with MH.
Blood Platelets* ; Colitis ; Colitis, Ulcerative* ; Humans ; Incidence ; Inflammation ; Inflammatory Bowel Diseases ; Kaplan-Meier Estimate ; Multivariate Analysis ; Observational Study ; Platelet Count* ; Prospective Studies ; Recurrence* ; Risk Factors ; Ulcer*

BACKGROUND/AIMS: Although studies using conventional animal models have shown that specific stressors cause irritable bowel syndrome (IBS), it is unclear whether depression itself causes IBS. Our aim was to establish a rat model to determine if depression itself promotes the onset of IBS and to elucidate the role of gut microbiota in brain-gut axis pathogenesis during coincident depression and IBS. METHODS: Rat models of depression were induced using our shuttle box method of learned helplessness. Visceral hypersensitivity was evaluated by colorectal distension (CRD) to diagnose IBS. Gut microbiota compositions were analyzed using high-throughput sequencing. In the subanalysis of rats without depression-like symptoms, rats with posttraumatic stress disorder (PTSD) were also examined. RESULTS: The threshold value of CRD in depressed rats was significantly lower than that in control rats. Microbial community analysis of cecal microbiota showed that the relative abundance of Clostridiales incertae sedis, the most prevalent microbe, was significantly lower in depressed rats than in control rats. The distribution pattern of the microbiota clearly differed between depressed rats and control rats. Neither visceral hypersensitivity nor the composition of gut microbiota was altered in rats with PTSD-like phenotypes. CONCLUSIONS: Our rat model of depression is useful for clarifying the effect of depression on IBS and suggests that depression itself, rather than specific stressors, promotes the onset of IBS. Further, we provided evidence that various psychiatric diseases, viz., depression and PTSD, are associated with unique gut microbiota profiles, which could differentially affect the onset and progression of coincident IBS.
Animals ; Clostridiales ; Depression ; Dysbiosis ; Gastrointestinal Microbiome ; Helplessness, Learned ; Hypersensitivity ; Irritable Bowel Syndrome ; Methods ; Microbiota ; Models, Animal ; Phenotype ; Rats ; Stress Disorders, Post-Traumatic

To screen for additional treatment targets against tongue cancer, we evaluated the contributions of extracellular signal-related kinase (ERK), AKT and ezrin in cancer development. Immunohistochemical staining showed that ERK and ezrin expressions were significantly higher in invasive squamous cell carcinoma than in carcinoma in situ. To investigate the roles of ERK and ezrin in cancer development, we used the non-woven silica fibre sheet Cellbed with a structure resembling the loose connective tissue morphology in a novel 3D culture system. We confirmed that the 3D system using Cellbed accurately mimicked cancer cell morphology in vivo. Furthermore, cell projections were much more apparent in 3D-cultured tongue cancer cell lines than in 2D cultures. Typically, under conventional 2D culture conditions, F-actin and cortactin are colocalized in the form of puncta within cells. However, in the 3D-cultured cells, colocalization was mainly observed at the cell margins, including the projections. Projections containing F-actin and cortactin colocalization were predicted to be invadopodia. Although suppressing ezrin expression with small interfering RNA transfection caused no marked changes in morphology, cell projection formation was decreased, and the tumour thickness in vertical sections after 3D culture was markedly decreased after suppressing ERK activity because both the invasion ability and proliferation were inhibited. An association between cortactin activation as well as ERK activity and invadopodia formation was detected. Our novel 3D culture systems using Cellbed™ are simple and useful for in vitro studies before conducting animal experiments. ERK contributes to tongue cancer development by increasing both cancer cell proliferation and migration via cortactin activation.
Carcinoma in Situ ; metabolism ; pathology ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Cell Culture Techniques ; methods ; Cell Movement ; Cell Proliferation ; Cytoskeletal Proteins ; metabolism ; Extracellular Signal-Regulated MAP Kinases ; metabolism ; Humans ; Neoplasm Invasiveness ; pathology ; Phosphorylation ; Podosomes ; pathology ; Proto-Oncogene Proteins c-akt ; metabolism ; Silicon Dioxide ; Tongue Neoplasms ; metabolism ; pathology ; Tumor Cells, Cultured