Katsuyoshi Ando

A Bamboo Joint-Like Appearance is a Characteristic Finding in the Upper Gastrointestinal Tract of Crohn's Disease Patients: A Case-Control Study.

Abstract The clinical importance of Crohns disease (CD)-specific lesions in the upper gastrointestinal tract (upper GIT) has not been sufficiently established. The aim of this case-control study is to investigate the characteristic findings of CD in the upper GIT. In 2740 patients who underwent gastroduodenoscopy at Asahikawa Medical University between April 2011 and December 2012, 81 CD patients, 81 gender- and age-matched non-IBD patients, and 66 ulcerative colitis (UC) patients were investigated in the present study. (1) The diagnostic ability and odds ratio of each endoscopic finding (a bamboo joint-like appearance in the cardia, erosions, and/or ulcers in the antrum, notched signs, and erosions and/or ulcers in the duodenum) were compared between the CD and non-IBD patients or UC patients. (2) The interobserver agreement of the diagnosis based on the endoscopic findings was evaluated by 3 experienced and 3 less-experienced endoscopists. The incidence of detecting a bamboo joint-like appearance, notched signs, and erosions and/or ulcers in the duodenum was significantly higher in the CD patients than in the non-IBD and UC patients. In addition, the diagnostic ability and odds ratio of a bamboo joint-like appearance for CD were higher than those for the other findings. Kendalls coefficients of concordance in the group of experienced and less-experienced endoscopists were relatively high for a bamboo joint-like appearance (0.748 and 0.692, respectively). A cardiac bamboo joint-like appearance is a useful finding for identifying high-risk groups of CD patients using only gastroduodenoscopy.

Reduction of E-cadherin by human defensin-5 in esophageal squamous cells.

Barretts esophagus (BE) is metaplastic columnar epithelium converted from normal squamous epithelia in the distal esophagus that is thought to be a precancerous lesion of esophageal adenocarcinoma. BE is attributed to gastroesophageal reflux disease (GERD), and therefore gastric acid or bile acids are thought to be factors that cause epithelial cell damage and inflammation in the gastro-esophageal junction. The decrease of adherent junction molecules, E-cadherin has been reported to be associated with the progression of the Barretts carcinoma, but the initiation of BE is not sufficiently understood. BE is characterized by the presence of goblet cells and occasionally Paneth cells are observed at the base of the crypts. The Paneth cells possess dense granules, in which human antimicrobial peptide human defensin-5 (HD-5) are stored and secreted out of the cells. This study determined the roles of HD-5 produced from metaplastic Paneth cells against adjacent to squamous cells in the gastro-esophageal junction. A human squamous cell line Het-1A, was incubated with the synthetic HD-5 peptide as a model of squamous cell in the gastro-esophageal junctions, and alterations of E-cadherin were investigated. Immunocytochemistry, flowcytometry, and Western blotting showed that the expression of E-cadherin protein was decreased. And a partial recovery from the decrease was observed by treatment with a CD10/neprilysin inhibitor (thiorphan). In conclusion, E-cadherin expression in squamous cells was reduced by HD-5 using in vitro experiments. In gastro-esophageal junction, HD-5 produced from metaplastic Paneth cells may therefore accelerate the initiation of BE.

Decreased numbers of vascular networks and irregular vessels on narrow-band imaging are useful findings for distinguishing intestinal lymphoma from lymphoid hyperplasia

BACKGROUND No method for sufficiently making the differential diagnosis of intestinal lymphoma resembling lymphoid hyperplasia (LH) on endoscopy has yet been established. OBJECTIVE The aim of this study was to evaluate the usefulness of narrow-band imaging (NBI) in diagnosing intestinal lymphoma. DESIGN Prospective study. SETTING Single-center study. PATIENTS Sixty-one patients with primary or systemic lymphoma were enrolled in this study. INTERVENTIONS The terminal ileum and entire colon were observed by using conventional endoscopy. NBI was subsequently performed when small polypoid lesions were detected. A decrease in the number of vascular networks (DVNs) and the presence of irregular vessels on the surface of the epithelia were defined as characteristic findings of intestinal lymphoma. The diagnostic accuracy of these 2 findings in distinguishing intestinal lymphoma from LH was examined. MAIN OUTCOME MEASUREMENTS The ability to use NBI to distinguish intestinal lymphoma from LH. RESULTS Two hundred ninety-four small polypoid lesions, including 59 lymphomas and 235 LH lesions, were detected. The rates of detecting DVNs and the presence of irregular vessels were significantly higher in the lymphoma samples (81.4% and 62.7%) than in the LH samples (25.5% and 4.7%). Based on these findings, the diagnostic accuracy, sensitivity, specificity, and positive and negative predictive values for differentiating intestinal lymphoma from LH were 88.8%, 62.7%, 95.3%, 77.1%, and 91.1%, respectively, which are significantly higher than those of conventional endoscopy. LIMITATIONS Single-center study. CONCLUSION DVNs and the presence of irregular vessels on NBI are thus considered to be useful findings for differentiating intestinal lymphoma from benign LH.

Heterogeneous Nuclear Ribonucleoprotein A1 Improves the Intestinal Injury by Regulating Apoptosis Through Trefoil Factor 2 in Mice with Anti-CD3–induced Enteritis

Background:The role of hnRNP A1 in the onset of intestinal inflammation remains unclear. This study investigated the function of hnRNP A1 in mice enteritis models. Methods:C57Bl6/J mice were intraperitoneally injected with anti-CD3 antibodies to develop enteritis. In the DSS-induced colitis group, the mice were allowed free access to 3% DSS solution in their drinking water for 5 days. 3H-mannitol flux and complementary DNA array tests were used to assess the intestinal barrier function and messenger RNA (mRNA) expression, respectively. Real-time PCR was performed after immunoprecipitation with anti-hnRNP antibodies to determine the specific mRNA binding of hnRNP A1. Results:The hnRNP A1 expression was increased in the intestine of the mouse at 24 hours after treatment with anti-CD3 antibodies and 5 days after starting DSS administration. Small interfering RNA (siRNA) against hnRNP A1 exacerbated the intestinal injuries in both models. According to the microarray analysis, trefoil factor 2 (TFF2) was identified as a candidate molecule targeted by hnRNP A1 in the anti-CD3 antibody–induced enteritis group. Moreover, the binding between hnRNP A1 and TFF2 mRNA significantly increased in the enteritis mice, and the administration of siRNA against either hnRNP A1 or TFF2 exacerbated the degree of intestinal injury. In the DSS-induced colitis group, treatment with the siRNA of hnRNP A1 worsened the intestinal injury, while the expression of TFF3 did not change. Conclusions:hnRNP A1 improves intestinal injury in anti-CD3 antibody–induced enteritis mice through the upregulation of TFF2, which regulates apoptosis and enhances epithelial restoration, whereas this molecule ameliorates DSS-induced colitis through a different pathway.

The incidence and risk factors of venous thromboembolism in Japanese inpatients with inflammatory bowel disease: a retrospective cohort study

Background/Aims Venous thromboembolism (VTE) is a major extraintestinal manifestation in inflammatory bowel disease (IBD), regarded as an independent risk factor for VTE according to reports from Western countries. However, the incidence and risk factors of VTE in Asian IBD patients are not fully understood. We aimed to reveal the incidence and risk factors of VTE in Japanese IBD inpatients. Methods The incidence of VTE in inpatients with IBD (n=340), gastrointestinal cancers (n=557), and other gastrointestinal diseases (n=569) treated at our hospital from 2009 to 2013 was retrospectively investigated. The characteristics and laboratory data of IBD inpatients with and without VTE were compared in univariate and multivariate analyses. Clinical courses of VTE in IBD were surveyed. Results VTE was detected in 7.1% of IBD inpatients, significantly higher than in gastrointestinal cancer inpatients (2.5%) and inpatients with other gastrointestinal diseases (0.88%). The incidence of VTE in ulcerative colitis (UC) patients (16.7%) was much higher than that in those with Crohns disease (3.6%). In the univariate analysis, the risk factors were an older age, central venous catheter, prednisolone, surgery, low serum albumin, high serum C-reactive protein and D-dimer. According to a multivariate analysis, >50 years of age and surgery were the only risk factors. The in-hospital mortality rate of IBD inpatients with VTE was 4.2%. Conclusions The incidence of VTE with IBD, especially UC, was found to be high compared with other digestive disease, which was almost equivalent to that of Western countries. The efficacy of prophylaxis needs to be investigated in Asian IBD patients.

Minute duodenal metastasis in a patient with thoracic esophageal squamous cell carcinoma successfully treated with chemoradiotherapy

An 84-year-old man with a history of distal gastrectomy for the treatment of gastric cancer presented with epigastric pain and underwent esophagogastroduodenoscopy. Visualization showed a large tumor in the esophagus (Figure 1A) and minute elevation with whitish granules in the duodenum (Figure 1B). Narrow-band imaging with magnified endoscopy (NBI-ME) showed enlarged villous structures with white vesicles and enlarged and meandering superficial vessels without irregularity (Figure 1C). This article is protected by copyright. All rights reserved.

Pilot study of endoscopic retrograde 3-dimensional – computed tomography enteroclysis for the assessment of Crohn’s disease

Purpose Endoscopic retrograde ileography (ERIG) is developed in our institute and applied clinically for the diagnosis and assessment of the Crohn’s disease activity. We have further improved the technique using 3-dimensional – computed tomography enteroclysis (3D-CTE) and conducted a retrospective study to determine the feasibility and the diagnostic value of endoscopic retrograde 3D-CTE (ER 3D-CTE) in Crohn’s disease patients in a state of remission. Methods Thirteen Crohn’s patients were included in this pilot study. CTE was performed after the infusion of air or CO2 through the balloon tube following conventional colonoscopy. The primary endpoint of this study was to assess the safety of this method. Secondarily, the specific findings of Crohn’s disease and length of the visualized small intestine were assessed. Results The procedures were completed without any adverse events. Gas passed through the small intestine and enterographic images were obtained in 10 out of 13 cases, but, in the remaining patients, insertion of the balloon tubes into the terminal ileum failed. Various features specific to Crohn’s disease were visualized using ER 3D-CTE. A cobble stone appearance or hammock-like malformation was specific and effective for diagnosing Crohn’s disease and the features of anastomosis after the surgical operations were also well described. Therefore, this technique may be useful after surgery. Conclusion In this study, ER 3D-CTE was performed safely in Crohn’s disease patients and may be used for the diagnosis and follow-up of this disease.

Sa2069 Polyphosphate is a Novel Active Molecule Derived From Lactobacillus brevis That Contributes to the Maintenance of Intestinal Homeostasis and the Improvement of Intestinal Injury in Acute and Chronic Experimental Colitis

P were examined with western blotting and a mannitol flux study, respectively. 2. Cell surface molecules of intestinal epithelia were separately blocked by their inhibitors or neutralizing antibodies and the change of the function of the effective molecule was tested to identify the epithelial sensing system for poly P. 3. Histological severity, cytokine induction in the colon, and the survival rate in DSS (3-4%) -induced acute colitis mice treated with intra-rectal administrations of poly P was examined. Furthermore, in the chronic phase of DSS- induced colitis mouse induced by DSS, the alterations of histological severity, cytokine induction and the activations of cell signal transductions by the intra-rectal administration of the poly P were examined. Results: 1. The synthesized poly P induced HSP27, phosphorylated p38 MAPK mouse intestinal epithelia, and suppressed intestinal permeability under oxidant stress. 2. These poly P functions were reduced by the inhibitor for integrin B1. 3. The daily intra-rectal administration of poly P improved the inflammation and survival in the acute colitis model. In chronic experimental colitis, poly P reduced the NF-kB activity that have become excessively activated in chronic experimental colitis and also improved the intestinal injury of the mouse colon. Conclusion: These findings suggest that poly P plays an important role in maintaining intestinal homeostasis and improving both acute and chronic inflammation through the integrin-p38 MAPK pathway, which is a novel system for mediating host-bacterial interactions.