Shin Kashima

The diagnostic accuracy of high-resolution endoscopy, autofluorescence imaging and narrow-band imaging for differentially diagnosing colon adenoma.

BACKGROUND AND STUDY AIMS Conventional colonoscopy can result in unnecessary biopsy or endoscopic resection due to its inability to distinguish adenomas from hyperplastic polyps. This study therefore evaluated the efficacy of high-resolution endoscopy (HRE), autofluorescence imaging (AFI), and narrow-band imaging (NBI) in discriminating colon adenoma from hyperplastic polyps. PATIENTS AND METHODS This was a prospective multicenter study in patients undergoing AFI and NBI examinations. HRE, AFI, and NBI images were classified into two groups based on morphological characteristics, the predominant color intensities, and the visibility of meshed capillary vessels, respectively. Each of the endoscopic photographs were independently evaluated by a single endoscopist. The images were then assessed by three specialists and three residents, the latter having performed < 500 colonoscopies and < 30 NBI and AFI examinations. Diagnostic test statistics were calculated to compare the accuracy in differentiating colon adenoma from hyperplastic polyps for each method. RESULTS A total of 183 patients were enrolled in the study and 339 adenomas and 85 hyperplastic polyps were identified. AFI and NBI could distinguish adenoma from hyperplastic polyps with an accuracy of 84.9 % and 88.4 %, respectively, whereas HRE exhibited an accuracy of 75.9 %. In the 358 lesions in which the AFI diagnosis was consistent with that of NBI, the accuracy, sensitivity, and specificity were high, at 91.9 %, 92.7 %, and 92.9 %, respectively. During the study comparing specialists and residents, AFI and NBI dramatically improved the diagnostic accuracy of residents from 69.1 % to 86.1 % and 84.7 %, respectively. CONCLUSIONS Both AFI and NBI are considered to be feasible tools that can discriminate colon adenoma from hyperplastic polyps, and their use may be particularly beneficial for less-experienced endoscopists.

Back-to-Back Comparison of Auto-Fluorescence Imaging (AFI) Versus High Resolution White Light Colonoscopy for Adenoma Detection

BackgroundSome patients under close colonoscopic surveillance still develop colorectal cancer, thus suggesting the overlook of colorectal adenoma by endoscopists. AFI detects colorectal adenoma as a clear magenta, therefore the efficacy of AFI is expected to improve the detection ability of colorectal adenoma. The aim of this study is to determine the efficacy of AFI in detecting colorectal adenoma.MethodsThis study enrolled 88 patients who underwent colonoscopy at Asahikawa Medical University and Kushiro Medical Association Hospital. A randomly selected colonoscopist first observed the sigmoid colon and rectum with conventional high resolution endosopy (HRE). Then the colonoscopist changed the mode to AFI and handed to the scope to another colonoscopist who knew no information about the HRE. Then the second colonoscopist observed the sigmoid colon and rectum. Each colonoscopist separately recorded the findings. The detection rate, miss rate and procedural time were assessed in prospective manner.ResultsThe detection rate of flat and depressed adenoma, but not elevated adenoma, by AFI is significantly higher than that by HRE. In less-experienced endoscopists, AFI dramatically increased the detection rate (30.3%) and reduced miss rate (0%) of colorectal adenoma in comparison to those of HRE (7.7%, 50.0%), but not for experienced endoscopists. The procedural time of HRE was significantly shorter than that of AFI.ConclusionsAFI increased the detection rate and reduced the miss rate of flat and depressed adenomas. These advantages of AFI were limited to less-experienced endoscopists because experienced endoscopists exhibited a substantially high detection rate for colorectal adenoma with HRE.

Biomarkers predicting development of metachronous gastric cancer after endoscopic resection: an analysis of molecular pathology of Helicobacter pylori eradication

Metachronous gastric cancer (MGC) after endoscopic resection (ER) of gastric cancer still occurs to some degree even after Helicobacter pylori (H. pylori) treatment. We evaluated whether two biomarkers related to carcinogenesis expressed in intestinal metaplasia (IM) become predictors for MGC development after eradication. We performed a hospital‐based, case–control study of 75 patients, including 50 mucosal cancer patients who had undergone ER (Group DYS), and 25 age‐ and sex‐matched chronic gastritis patients for whom H. pylori had been successfully eradicated (control). Additionally, Group DYS patients were divided into two groups: 25 successfully H. pylori‐eradicated (eradicated group) and 25 un‐eradicated patients (persistent group). All patients were followed for 1 year. We analyzed microsatellite instability (MSI) and immunoperoxidase assays using a monoclonal antibody for the colonic phenotype (Das‐1). Both MSI and Das‐1 reactivity in IM were significantly higher in Group DYS than in the control (p < 0.05 and p < 0.01, respectively). MSI and Das‐1 reactivity were strong and independent predictors for gastric cancer (OR = 7.09, 95% CI 1.27–39.6, p = 0.03 for MSI and OR = 4.96, 95% CI 1.64–15.0, p = 0.005 for Das‐1 reactivity). The incidence of MSI tended to decrease in the eradicated group (p = 0.07), but not in the persistent group. The Das‐1 immunoreactivity in IM also declined in both the eradicated group and the control. Interestingly, all MGCs after ER were positive for MSI or Das‐1 reactivity. MSI or Das‐1 reactivity in IM strongly predicts the development of MGC. Patients in whom these biomarkers persist after eradication may therefore have a high risk of developing MGC.

Polyphosphate, an active molecule derived from probiotic Lactobacillus brevis, improves the fibrosis in murine colitis

Inflammatory bowel disease frequently causes intestinal obstruction because of extensive fibrosis. This study investigated whether polyphosphate (poly P), an active molecule derived from Lactobacillus brevis, could improve the fibrosis in a model of chronic colitis. In this study, dextran sodium sulfate (DSS)-induced chronic colitis models and trinitrobenzene sulfonic acid (TNBS)-induced colitis models were used as models of fibrosis. To clarify the mechanism responsible for the observed effects, Caco-2/brush border epithelial (BBE) and naive T helper lymphocyte (THP)-1 cells were treated with lipopolysaccharide (LPS) to induce inflammation. Non-cancer human colon fibroblast (CCD-18) cells were treated with transforming growth factor beta 1 (TGF-β1) to induce fibrosis. The expression levels of fibrosis- and inflammation-associated molecules were evaluated by both a Western blotting analysis and reverse transcriptase-polymerase chain reaction (RT-PCR). The histologic inflammation and fibrosis were significantly improved in the group administered poly P in both the DSS and TNBS colitis models. The levels of interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) were significantly decreased by poly P treatment. The expression levels of TGF-β1 and collagens in the colitis mice were decreased by poly P. The LPS-induced expressions of IL-1β and TGF-β1 in Caco-2/BBE cells and of TNF-α in THP-1 cells were reduced by poly P treatment. Poly P did not affect the expression of collagens and connective tissue growth factor in the CCD-18 cells. In conclusion, poly P suppresses intestinal inflammation and fibrosis by downregulating the expression of inflammation- and fibrosis-associated molecules in the intestinal epithelium. The administration of poly P is therefore a novel option to treat fibrosis because of chronic intestinal inflammation.

A Randomized Study on the Effectiveness of Prophylactic Clipping during Endoscopic Resection of Colon Polyps for the Prevention of Delayed Bleeding

Backgrounds. The efficacy of clipping for preventing the delayed bleeding after the removal of colon polyps is still controversial. In order to clarify this efficacy, a randomized controlled study was performed. Methods. One hundred and fifty-six patients with colon neoplasms (288 lesions) were enrolled in the study. The patients were randomly divided into two groups: clipping or nonclipping groups using a sealed envelope method before the endoscopic resections. Eight specialists and nine residents were invited to perform this procedure. The risk factors and the rates of delayed bleeding after the endoscopic resections in each group were investigated. Results. There were no significant differences in the bleeding rate between the clipping and nonclipping groups, while the length of the procedure was significantly longer and the cost was higher in the clipping group than in the nonclipping group. The rate of bleeding was significantly higher in cases with polyps 2 cm or larger and with a longer procedure time, while none of the other factors affected the bleeding rate. Conclusions. This randomized controlled study revealed no significant effect of prophylactic clipping for preventing delayed bleeding after the endoscopic resection of colon polyps.

Infliximab Extends the Duration until the First Surgery in Patients with Crohn’s Disease

Background/Aims. While biological drugs are useful for relieving the disease activity and preventing abdominal surgery in patients with Crohns disease (CD), it is unclear whether the use of biological drugs in CD patients with no history of abdominal surgery is appropriate. We evaluated the effects of infliximab and other factors on extending the duration until the first surgery in CD patients on a long-term basis. Methods. The clinical records of 104 CD patients were retrospectively investigated. The cumulative nonoperation rate until the first surgery was examined with regard to demographic factors and treatments. Results. The 50% nonoperative interval in the 104 CD patients was 107 months. The results of a univariate analysis revealed that a female gender, the colitis type of CD, and the administration of corticosteroids, immunomodulators, or infliximab were factors estimated to improve the cumulative nonoperative rate. A multivariate analysis showed that the colitis type and administration of infliximab were independent factors associated with a prolonged interval until the first surgery in the CD patients with no history of abdominal surgery. Conclusions. This study suggests that infliximab treatment extends the duration until the first surgery in CD patients with no history of abdominal surgery. The early use of infliximab before a patient undergoes abdominal surgery is therefore appropriate.

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.

Probiotic-derived polyphosphate improves the intestinal barrier function through the caveolin-dependent endocytic pathway.

Probiotics exhibit beneficial functions for host homeostasis maintenance. We herein investigated the mechanism by which Lactobacillus brevis-derived poly P exhibited a beneficial function. Immunostaining indicated that poly P was captured in the plasma membrane via integrin β1 in Caco2/bbe cells. The uptake of poly P was reduced by the inhibition of integrin β1 as well as caveolin-1, a major component of lipid rafts. The function of poly P, including the induction of HSP27 and enhancement of the intestinal barrier function, was suppressed by the inhibition of caveolin-1, illustrating that the function of poly P was mediated by the endocytic pathway. High-throughput sequencing revealed that poly P induced tumor necrosis factor alpha-induced protein 3, which contributes to cytoprotection, including upregulation of the intestinal barrier function. The present study demonstrates a novel host-probiotic interaction through the uptake of bacterial substance into host cells, which is distinct from pattern recognition receptor pathways.

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.