847r capsule endoscopy findings in small bowel crohn's disease patients in clinical remission:...
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s(about half of the perimeter) of the anterior gastric wall was excised and replaced by a BAPpatch at the excision site. The BAP patch was composed of a 50:50 copolymer of polylacticacid and polycaprolactone reinforced with polyglycolic acid fibers. The materials weredesigned to degrade in about 6 to 8 weeks and had an air porosity of 95% or more to allowcells to easily penetrate. There was no prior cell seeding or other preparatory treatment forthe BAP patch. Four, eight, twelve weeks after implantation, the animals were respectivelyre-laparotomized and underwent resections of the whole stomach for exploration of thegraft sites by gross and histological studies. Result: All of the recipient pigs survived untilsacrifice without any decreases in oral intake. At 4-8 weeks, the graft site revealed ulcerreducing by the day. At 12 weeks, the graft site was indistinguishable from the native gastricwall. Histology at the site of the patch confirmed the growth of a mucosa into a villous-like form with submucosa and a proper muscle layer similar to that of the native wall. Subtledifferences were confirmed in much of the connective tissue, including somewhat reducedamounts of elastic fiber and smooth muscle density compared to the native gastric wall.Conclusion: The BAP could repair the defective gastric wall without complications andregenerate a neo gastric wall at 12 weeks after implantation. This newly designed substitutehas the potential for application as a novel treatment for gastric disease.
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Immediate Detection of Helicobacter Infection With a Novel ElectrochemicalSystem: Feasibility and Comparison of Diagnostic Yield WithImmunohistochemistry, 13C Urea Breath Test and Helicobacter Urease TestHelmut Neumann, Stefan Foertsch, Michael Vieth, Jonas Mudter, Rainer Kuth, Markus F.Neurath
Introduction: Helicobacter pylori-infection (H. pylori) affects about fifty percent of the generalpopulation and is associated with peptic ulcer diasese, non-cardia gastric adenocarcinomaand gastric lymphoma. Currently, diagnostic methods include breath tests, serology, stoolantigen tests, histology or the Helicobacter urease test (HUT®). Aim: To access the clinicalreliability of a new, electrochemical device for H. pylori detection. Material & Methods:Twenty consecutive patients undergoing upper gastrointestinal endoscopy were prospectivelyincluded in the study (14 female, 6 male; mean age 44.5 years, range 18-78 years). Thenewly developed electrochemical device for H. pylori detection consists of a working andreference electrode between which a biopsy sample was administered. Afterwards, acquiredvoltage-values were analysed for characteristics typical for H. pylori infection (ammonia).According to the updated Sydney classification, biopsies were taken from the gastric antrumand corpus for the electrochemicalH. pylori detection, HUT® (AstraZeneca,Wedel, Germany)and for immunohistochemistry (IHC). HUT® results were evaluated after 24 hours. Further-more, every patient received 13C-urea breath test. Detection rates for H. pylori were analysedblinded to IHC results, which was designated as the gold standard. Results: HUT® analysisrevealed a sensitivity of 100% and a specificity of 89%. 13C-urea breath test identified H.pylori positive patients with similar values (sensitivity: 100%; specificity 94.4%). The newlydeveloped electrochemical H. pylori detection method showed equivalent results comparedto IHC (sensitivity 100%, specifity 100%). Definitive results for H. pylori detection with thenew device were available within 10 seconds. Conclusion: In the present study, the newlydeveloped electrochemical H. pylori test was equivalent to IHC. Definitive results wereachieved immediately within 10 seconds. Therefore, the method appears to provide immedi-ate, definitive results and has the capability to facilitate bothH. pylori diagnosis and treatment.An ongoing equivalence controlled trial is now evaluating the test in a larger setting.
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The Role of a High Definition, Probe Based Confocal Laser Endomicroscopy(pCLE) System) in Diagnosing Smaller Indeterminate Colorectal Polyps InVivoAnna M. Buchner, Muhammad W. Shahid, Massimo Raimondo, Timothy A. Woodward,Michael B. Wallace
Background: The high resolution probe-based confocal laser endomicroscopy system (pCLE)allows imaging of surface colonic epithelium In Vivo. In colorectal polyps, this offers thepotential of immediate diagnosis and triage of small indeterminate polyps (1-9 mm) to eithernon-removal, or removal without histological confirmation of low grade adenomas. Thishas the potential to substantially reduce the morbidity and cost associated with polypectomyand histological confirmation. Aims: The aim of our study was to evaluate the accuracy ofpCLE for prediction of histology of small indeterminate colorectal polyps during screening/surveillance colonoscopy. Methods: Patients underwent probe based laser endomicroscopysystem with intravenous fluorescein sodium during routine colonoscopy. All polyps wereimages with standard HD white light, narrow band imaging, followed by pCLE. The storedpCLE images of small (1-9 mm) colorectal polyps were scored for neoplasia using establishedcriteria (Buchner et al. Gastro [in press] by a single endoscopist with experience of > 300confocal exams. The reviewer was blinded to histopathology and endoscopic findings andcompared to a gold standard histopathology. Likewise, the pathologist was blinded to theconfocal findings. Results: A total 84 patients with 145 lesions were enrolled in the study.All were Paris classification 1p or 1s (pedunculated or sessile; no flat lesions). The presenceof neoplasia for all smaller lesions 1-9 mm, as well as subgroups of very small (1-5mm)and larger (6-9mm) were predicted with a high level of accuracy (Table 1). In particular,pCLE predicted neoplasia in 100% of 6-9mm adenomas, and the absence of neoplasia inalmost 91% of non-neoplastic polyps. Conclusions: The pCLE system allows accurate dia-gnosis of smaller colorectal lesions and thus has the potential to direct further endoscopicdecisions such as avoidance of unnecessary polypectomies or confirmation of low gradeneoplasia without histology.
S-114AGA Abstracts
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Capsule Endoscopy Findings in Small Bowel Crohn's Disease Patients inClinical Remission: Correlation With the Crohn's Disease Activity Index,Faecal Calprotectin and S100A12Vipul Aggarwal, Andrew S. Day, Susan J. Connor, Steven T. Leach, Michael C. Grimm,Philip I. Craig
Background: Conventional parameters including clinical (Crohn's Disease Activity Index[CDAI]), blood tests, imaging and colonoscopy have limitations in accurately assessing CDremission. However, recent reports suggest that CD patients not in endoscopic remissionhave worse long-term outcomes and are more likely to clinically relapse. Capsule endoscopy(CE) is the most sensitive test to diagnose small bowel (SB) CD, however, no studies haveexamined its role in assessing disease remission. Therefore, the study aims were to (1) ReportCE findings in pts with small bowel CD in clinical remission and (2) Compare CE findingswith CDAI and C reactive protein (CRP) levels and specific faecal biomarkers, calprotectinand S100A12. Methods: Adult SB CD patients (without evidence of SB strictures) in clinicalremission (CDAI <150) were prospectively enrolled. CE studies (Olympus EndoCapsule)were reported using a Capsule Endoscopy Scoring Index (CESI) (Aliment Pharmacol Ther,2008, 27: 146). CESI divides the SB into tertiles & numerically assesses villous oedema,ulceration & stenosis. Endoscopic remission was CESI <135, mild inflammation 135-790and moderate-severe inflammation >790. Stool was collected for measurement of faecalcalprotectin and S100A12 and serum CRP was measured. CE scores were correlated withCDAI, CRP and faecal calprotectin and S100A12 levels. Results: 25 pts (12 M) median age42 yrs (range 20-61) were studied. At enrolment, median CDAI was 80 (50-140), CRP 7(2.2-15.1) (normal<5), calprotectin 295 mg/kg (2-6390) (normal <100) and S100A12 5mg/kg (0-2000) (normal<10). As assessed by CESI, 72% of pts in clinical remission hadinflammatory changes on CE and co-existent elevated faecal calprotectin levels. All pts withCESI<135 had normal calprotectin levels. In abnormal studies, the highest CESI score bytertile was in the 1st in 22%, the 2nd in 28% and the 3rd in 50%. No pt had stenosis.Spearman's correlation coefficient for CESI and calprotectin was 0.754 (p<0.0001) andS100A12 0.288 (NS) respectively. There was no correlation between CESI and CDAI orCRP. Conclusions: In small bowel CD pts assessed in clinical remission: (1) Many havesignificant ongoing inflammation distributed throughout the SB on CE; 2) Faecal calprotectinlevels may be useful in predicting mucosal inflammation and ongoing disease in these pts;3) These findings may have important clinical & therapeutic implications.
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Intestinal Microsomal Triglyceride Transfer Protein (MTP) Regulates CD1dFunction on the Intestinal Epithelium and Protects From Mortality in theOxazolone ModelTorsten Olszak, Sebastian Zeissig, Arthur Kaser, Nicholas O. Davidson, Richard S.Blumberg
Background & Aim: Natural Killer T (NKT) cells recognize lipid antigens presented byCD1d. MTP is an endoplasmic reticulum-resident protein which can transfer phospholipidsonto CD1d and regulate CD1d antigen presentation. We aimed to characterize the role ofCD1d and MTP in intestinal epithelial cells (IECs) in oxazolone colitis. Results:VcreERT2MTTPfl/fl mice were generated to allow for tamoxifen-induced deletion of MTP inIECs (MTP-KO). Oxazolone colitis led to rapid mortality of MTP-KOmice, while no mortalitywas observed in tamoxifen treated wildtype VcreERT2MTTPfl/fl mice or in MTP-KO micein the absence of oxazolone skin sensitization. Similar findings were made in the dextran-sodium sulfate induced colitis model. Inhibition of CD1d-restricted antigen presentation byi.v. injection with a monoclonal anti-CD1d antibody prevented mortality in MTP-KO mice.Microarray analysis of intestinal tissues 6 hours after rectal oxazolone challenge revealedstrong induction of gene expression related to innate immunity (IL-1α, IL-1β, cyclooxygenase2, S100A9) with significantly higher expression in tissues from MTP-KO mice. Baselineexpression of several heat-shock proteins (HSPs) involved in barrier protection and immunitywas decreased in MTP-KO mice with further down-regulation upon oxazolone administra-tion. CD1d crosslinking and coculture with NKT cells increased HSP110 expression inwildtype IECs. Finally, an adenovirus encoding HSP110, but not the control LacZ containingadenovirus rescuedmortality observed in tamoxifen treated VcreERT2MTTPfl/fl mice.Conclu-sion: IECs have an MTP- and CD1d-dependent protective role in oxazolone colitis whichis mediated at least in part by HSP110 while hematopoetic cells drive colitis in a CD1d-restricted manner.
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Adalimumab for Induction of Clinical Remission in Moderately to SeverelyActive Ulcerative ColitisWalter Reinisch, William J. Sandborn, Daniel W. Hommes, Geert R. D'Haens, Stephen B.Hanauer, Stefan Schreiber, Remo Panaccione, Richard N. Fedorak, Mary Beth Tighe,Bidan Huang, Andreas Lazar
Aim: A multicenter, randomized, double-blind, placebo-controlled study to assess the efficacyand safety of adalimumab (ADA), a fully human anti-TNF monoclonal antibody, for theinduction of clinical remission in anti-TNF naïve patients with moderately to severely activeulcerative colitis. Methods: Adult patients with Mayo score ≥6 points and endoscopicsubscore≥2 points despite treatment with corticosteroids and/or immunosuppressants wereenrolled. 186 patients were randomized in a 1:1 ratio to subcutaneous treatment withADA160/80 (160mg at Week 0, 80mg at Week 2, 40mg at Weeks 4 and 6) or placebo.