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Signal Transduction and Targeted Therapy 2024年第7期9卷 2835-2836页

作者： Imke Atreya markus f.neurath Department of Medicine 1 University Hospital of ErlangenFriedrich-Alexander University Erlangen-NürnbergErlangenGermany Deutsches Zentrum Immuntherapie(DZI) ErlangenGermany

In a recent study published in Nature,York and coworkers identified the immunometabolic regulation of mono-unsaturated fatty acid(MUfA)pools and the subsequent increase in sphingolipid biosynthesis in TLR2-activated macrophages as an important link between impaired IL-10 signaling and the development of intestinal inflammation.1 Thus,targeted interference with the newly identified IL-10/MUfA/sphingolipid axis appears as a promising strategy to restore immunometabolic homeostasis in the intestine of patients with inflammatory bowel diseases(IBD).

关键词： homeostasis impaired intestine

New endoscopic approaches in IBD

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World Journal of Gastroenterology 2011年第1期17卷 63-68页

作者： Helmut Neumann markus f neurath Jonas Mudter Department of Medicine I University of Erlangen-Nuremberg91054 ErlangenGermany

Recent advances in endoscopic imaging techniques have revolutionized the diagnostic approach of patients with inflammatory bowel disease(IBD).New,emerging endoscopic imaging techniques visualized a plethora of new mucosal details even at the cellular and subcellular *** review offers an overview about new endoscopic techniques,including chromoendoscopy,magnification endoscopy,spectroscopy,confocal laser endomicroscopy and endocytoscopy in the face of IBD.

关键词：鸡传染性法氏囊病内窥镜成像技术细胞水平激光共聚焦诊断方法 IBD 可视化

Cancer risk in IBD: How to diagnose and how to manage DALM and ALM

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World Journal of Gastroenterology 2011年第27期17卷 3184-3191页

作者： Helmut Neumann Michael Vieth Cord Langner markus f neurath Jonas Mudter Department of Medicine 1 Department of SurgeryUniversity of Erlangen-Nuremberg Ulmenweg 1891054 ErlangenGermany Institute of Pathology Klinikum Bayreuth GmbHPreuschwitzer Str. 10195445 BayreuthGermany Institute of Pathology Medical University of GrazAuenbruggerplatz 25A-8036 Graz Austria

The risk of developing neoplasia leading to colorectal cancer is significantly increased in ulcerative colitis (UC) and most likely in Crohn's disease. Several endoscopic surveillance strategies have been implemented to identify these lesions. The main issue is that colitisassociated neoplasms often occurs in flat mucosa, often being detected on taking random biopsies rather than by identification of these lesions via endoscopic imaging. The standard diagnostic procedure in long lasting UC is to take four biopsies every 10 cm. Image enhancement methods, such as chromoendoscopy and virtual histology using endomicroscopy, have greatly im- proved neoplasia detection rates and may contribute toreduced random biopsies by taking targeted "smart" biopsies. Chromoendoscopy may effectively be performed by experienced endoscopists for routine screening of UC patients. By contrast, endomicroscopy is often only available in selected specialized endoscopic centers. Importantly, advanced endoscopic imaging has the poten- tial to increase the detection rate of neoplasia whereas the interplay between endoscopic experience and interpretation of histological biopsy evaluation allows the physician to make a proper diagnosis and to find the appropriate therapeutic approach. Colitis-associated intraepithelial neoplasms may occur in flat mucosa of endoscopically normal appearance or may arise as dysplasia-associated lesion or mass (DALM), which may be indistinguishable from sporadic adenomas in healthy or non-colitis mucosa [adenoma-like mass (ALM)]. The aim of this review was to summarize endoscopic and histological characteristics of DALM and ALM in the context of therapeutic procedures.

关键词：诊断程序 ALM 风险 IBD 溃疡性结肠炎管理癌症治疗程序

Molecular mechanism of action of anti-tumor necrosis factor antibodies in inflammatory bowel diseases

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World Journal of Gastroenterology 2016年第42期22卷 9300-9313页

作者： Ulrike Billmeier Walburga Dieterich markus f neurath Raja Atreya Medical Clinic 1 Friedrich-Alexander-Universit?t Erlangen-Nürnberg

Anti-tumor necrosis factor(TNf) antibodies are successfully used in the therapy of inflammatory bowel diseases(IBD). However, the molecular mechanism of action of these agents is still a matter of debate. Apart from neutralization of TNf, influence on the intestinal barrier function, induction of apoptosis in mucosal immune cells, formation of regulatory macrophages as well as other immune modulating properties have been discussed as central features. Nevertheless, clinically effective anti-TNf antibodies were shown to differ in their mode-of-action in vivo and in vitro. furthermore, the anti-TNf agent etanercept is effective in the treatment of rheumatoid arthritis but failed to induce clinical response in Crohn's disease patients, suggesting different contributions of TNf in the pathogenesis of these inflammatory diseases. In the following, we will review different aspects regarding the mechanism of action of anti-TNf agents in general and analyze comparatively different effects of each antiTNf agent such as TNf neutralization, modulation of the immune system, reverse signaling and induction of apoptosis. We discuss the relevance of the membranebound form of TNf compared to the soluble form for the immunopathogenesis of IBD. furthermore, we review reports that could lead to personalized medicine approaches regarding treatment with antiTNf antibodies in chronic intestinal inflammation, by predicting response to therapy.

关键词： Mucosal 免疫学薄板 propria mononuclear 房间 Crohn’ s 疾病 Ulcerative 大肠炎 Transmembrane 肿瘤坏死因素 Apoptosis

Differential diagnosis in inflammatory bowel disease colitis:State of the art and future perspectives

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World Journal of Gastroenterology 2015年第1期21卷 21-46页

作者： Gian Eugenio Tontini Maurizio Vecchi Luca Pastorelli markus f neurath Helmut Neumann Gastroenterology and Digestive Endoscopy Unit IRCCS Policlinico San Donato20097 San Donato MilaneseItaly Department of Medicine I University of Erlangen-Nuremberg91054 ErlangenGermany Department of Biomedical Sciences for Health University of Milan20122 MilanoItaly

Distinction between Crohn's disease of the colonrectum and ulcerative colitis or inflammatory bowel disease(IBD) type unclassified can be of pivotal importance for a tailored clinical management,as each entity often involves specific therapeutic strategies and ***,no gold standard is available and the uncertainty of diagnosis may frequently lead to misclassification or repeated ***,we have performed a literature search to address the problem of differential diagnosis in IBD colitis,revised current and emerging diagnostic tools and refined disease classification ***,the differential diagnosis is an untangled issue,and the proper diagnosis cannot be reached in up to 10% of patients presenting with IBD *** topic is receiving emerging attention,as medical therapies,surgical approaches and leading prognostic outcomes require more and more disease-specific strategies in IBD *** optimization of standard diagnostic approaches based on clinical features,biomarkers,radiology,endoscopy and histopathology appears to provide only marginal ***,emerging diagnostic techniques in the field of gastrointestinal endoscopy,molecular pathology,genetics,epigenetics,metabolomics and proteomics have already shown promising *** advanced endoscopic imaging techniques and biomarkers can shed new light for the differential diagnosis of IBD,better reflecting diverse disease behaviors based on specific pathogenic pathways.

关键词： Crohn’s disease Ulcerative colitis Inflammatory bo

Double-balloon-enteroscopy-based endoscopic retrograde cholangiopancreatography in post-surgical patients

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World Journal of Gastroenterology 2011年第18期17卷 2302-2314页

作者： Martin Raithel Harald Dormann Andreas Naegel frank Boxberger Eckhart G Hahn markus f neurath Juergen Maiss Department of Medicine 1 University of Erlangen-Nürnberg Emergency Unit City Hospital Fürth Dean of the University Witten-Herdecke

AIM: To evaluate double balloon enteroscopy (DBE) in post-surgical patients to perform endoscopic retrograde cholangiopancreatography (ERCP) and interventions. METHODS: In 37 post-surgical patients, a stepwise approach was performed to reach normal papilla or enteral anastomoses of the biliary tract/pancreas. When conventional endoscopy failed, DBE-based ERCP was performed and standard parameters for DBE, ERCP and interventions were recorded. RESULTS: Push-enteroscopy (overall, 16 procedures) reached enteral anastomoses only in six out of 37 post-surgical patients (16.2%). DBE achieved a high rate of luminal access to the biliary tract in 23 of the remaining 31 patients (74.1%) and to the pancreatic duct (three patients). Among all DBE-based ERCPs (86 procedures), 21/23 patients (91.3%) were successfully treated. Interventions included ostium incision or papillotomy in 6/23 (26%) and 7/23 patients (30.4%), respectively. Biliary endoprosthesis insertion and regular exchange was achieved in 17/23 (73.9%) and 7/23 patients (30.4%), respectively. furthermore, bile duct stone extraction as well as ostium and papillary dilation were performed in 5/23 (21.7%) and 3/23 patients (13.0%), respectively. Complications during DBE-based procedures were bleeding (1.1%), perforation (2.3%) and pancreatitis (2.3%), and minor complications occurred in up to 19.1%. CONCLUSION: The appropriate use of DBE yields a high rate of luminal access to papilla or enteral anastomoses in more than two-thirds of post-surgical patients, allowing important successful endoscopic therapeutic interventions.

关键词：双气囊小肠手术患者胆管造影内镜胃镜检查

In vivo detection of mucosal healing-involved histiocytes by confocal laser endomicroscopy

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World Journal of Gastroenterology 2012年第32期18卷 4447-4449页

作者： Gheorghe Hundorfean Abbas Agaimy Mircea T Chiriac Walter GeiBdrfer Jochen Wacker markus f neurath Jonas Mudter Medical ClinicⅠ University of ErlangenNuremberg91054 ErlangenGermany Institute of Pathology University of Erlangen-Nuremberg91054 ErlangenGermany Microbiology Institute-Clinical Microbiology Immunology and HygieneUniversity of Erlangen-Nuremberg91054 ErlangenGermany Medical Clinic Ⅲ University of Erlangen-Nuremberg91054 ErlangenGermany

Histiocytes have a pivotal role in wound repair and intestinal epithelial recovery-the most important goal to sustain gut ***,an in vivo description of colonic histiocytes by confocal laser endomicroscopy(CLE) is ***,we report the case of a 45-yearsold male patient who was referred to our clinic with weight loss and a history of two consecutive Clostridium difficile colitis episodes,the latter cured 3 wk before present *** microbiology was *** colonoscopy showed atrophy and a light mucosal oedema in the distal *** on-going endoscopy,we performed a fluorescein-aided CLE which revealed large polygonal(histiocytes-like) cells with copious cytoplasm and large nuclei in the lamina propria of the sigmoid colon as well as regenerative epithelial *** assessment of biopsies from the same areas confirmed the endomicroscopical findings:Periodic acid-Schiff-and CD68-positive foamy histiocytes in the colonic lamina propria and an advanced epithelial *** stool microbiology was repeatedly negative and polymerase chain reaction-analysis from colonic biopsies could not detect any mRNA for Thropheryma whippleii and common pathogens,we interpreted this particular setting as a mucosal healing process after consecutive Clostridium difficile *** conclusion,by describing these colonic histiocytes,we highlight the clinical usefulness of CLE in describing the entity of histiocytes in vivo and in real-time during the process of post-infectious mucosal healing in the colon.

关键词：激光共聚焦组织细胞愈合过程肠黏膜内检测内镜梭状芽孢杆菌结肠镜

Retrograde inspection vs standard forward view for the detection of colorectal adenomas during colonoscopy: A back-to-back randomized clinical trial

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World Journal of Gastroenterology 2020年第16期26卷 1962-1970页

作者： Timo Rath Lukas Pfeifer Clemens Neufert Andreas Kremer Moritz Leppkes Arthur Hoffman markus f neurath Steffen Zopf Department of Internal Medicine 1 Division of GastroenterologyLudwig Demling Endoscopy Center of ExcellenceFriedrich-Alexander-UniversityErlangen NuernbergErlangen 91054Germany Department of Internal Medicine Division of GastroenterologyKlinikum AschaffenburgAschaffenburg 63739Germany Department of Internal Medicine Division of GastroenterologyKlinikum FürthFürth 90766Germany

BACKGROUND The adenoma detection rate(ADR)is inversely associated with the incidence of interval colorectal cancer and serves as a benchmark quality criterion during screening ***,adenoma miss rates reach up to 26%and studies have shown that a second inspection of the right colon in retroflected view(RfV)can increase *** To assess whether inspection of the whole colon in RfV compared to standard forward view(SfV)can increase *** Patients presenting for screening or surveillance colonoscopy were invited to participate in this randomized controlled trial and randomized into two *** RfV arm colonoscopy was initially performed with SfV,followed by a second inspection of the whole colon in *** the SfV arm first withdrawal was performed with SfV,followed by a second inspection of the whole colon again with ***,size and morphology of polyps found during first and second inspection in each colonic segment were recorded and all polyps were removed and sent for histopathology in separate *** Two hundred and five patients were randomly assigned to the RfV(n=101)and SfV(n=104)*** the RfV arm,both polyp detection rate(PDR)and ADR were increased under second inspection in RfV(PDR 1st SfV:39.8%,PDR 2nd RfV:46.6%;ADR 1st SfV:35.2%,ADR 2nd RfV:42%).Likewise,in the SfV arm,PDR and ADR were increased under second inspection(PDR 1st SfV:37.5%,PDR 2nd SfV:46.6%;ADR 1st SfV:34.1%,ADR 2nd SfV:44.3%)with no significant differences in ADR and PDR between the SfV and RfV *** number of adenomas per patient(APP)was increased in the RfV and SfV(APP RfV arm:1st SfV:1.71;2nd RfV:2.38;APP SfV arm:1st SfV:1.83,2nd SfV:2.2).The majority of adenomas additionally found during second inspection in RfV or in SfV were located in the transverse and left-sided colon and were>5 mm in *** Second inspection of the whole colon leads to increased adenoma detection with no differences between SfV and ***,increased detection is mos

关键词： Colorectal cancer Adenoma Adenoma detection rate Colonoscopy

Colon cancer and the immune system:The role of tumor invading T cells

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World Journal of Gastroenterology 2006年第45期12卷 7233-7238页

作者： Maximilian Waldner Carl C Schimanski markus f neurath I. Department of Medicine University of Mainz Mainz Germany

Colon cancer is still one of the leading causes of cancer death worldwide. Although the host immune system has been shown to react against tumor cells, mainly through tumor infi ltrating lymphocytes and NK cells, tumor cells may utilize different ways to escape anti-tumor immune response. Tumor infi ltration of CD8+ and CD4+ (T-bet+) effector T cells has been attributed to a beneficial outcome, and the enhancement of T cell activation through T cell receptor stimulation and co-stimulatory signals provides promising strategies for immunotherapy of colon cancer. Growing evidence supports a role for the fas/fasL system in tumor immunology, although the mechanisms and consequences of fasL activation in colon cancer are not completely understood. In animal models, depletion of regulatory T cells (CD4+ CD25+ T cells) can enhance the anti-tumor immune response under certain conditions. Taken together, recent insights in the immune reaction against colon carcinoma have provided new approaches to immunotherapy, although much remains to be learned about the exact mechanisms.

关键词：结肠癌淋巴细胞免疫系统肿瘤免疫疗法

from the surface to the single cell: Novel endoscopic approaches in inflammatory bowel disease

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World Journal of Gastroenterology 2015年第40期21卷 11260-11272页

作者： Timo Rath Gian Eugenio Tontini markus f neurath Helmut Neumann Department of Medicine 1 Division of GastroenterologyUniversity Hospital Erlangen Gastroenterology and Digestive Endoscopy Unit IRCCS Policlinico San Donato20097 San Donato MilaneseItaly

Inflammatory bowel diseases(IBD) comprise the two major entities Crohn's disease and ulcerative colitis and endoscopic imaging of the gastrointestinal tract has always been an integral and central part in the management of IBD patients. Within the recent years,mucosal healing emerged as a key treatment goal in IBD that substantially decides about the clinical outcome of IBD patients,thereby demanding for a precise,timely and detailed endoscopic assessment of the mucosal inflammation associated with IBD. further,molecular imaging has tremendously expanded the clinical utility and applications of modern endoscopy,now encompassing not only diagnosis,surveillance,and treatment but also the prediction of individual therapy response. Within this review we describe novel endoscopic approaches and advanced endoscopic imaging methods for the diagnosis,treatment and surveillance of IBD patients. We begin by providing an overview over novel and advanced imaging techniques such as magnification endoscopy and dye-based and dye-less chromoendoscopy,endomicroscopy and endocytoscopy. We then describe how these techniques can be utilized for the precise and ultrastructural assessment of mucosal inflammation and dysplasia development associated with IBD and outline how they have enabled the endoscopist to gain insight onto the cellular level in real-time. finally,we provide an outlook on how molecular imaging has rapidly evolved in the recent past and can be used to make individual predictions about the therapeutic response towards biological treatment.

关键词： Gastrointestinal endoscopy Crohn’s disease Ulcerat