Apoptosis of T cells and the control of inflammatory bowel disease: therapeutic implications.
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Anti-Inflammatory Agents, Non-Steroidal↗
Biomedical subjects
M F Neurath
Publications and source records attributed to M F Neurath.
Chromoendoscopy in Barrett's oesophagus: is cresyl violet the magic bullet?
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Barrett Esophagus↗
[Endomicroscopy--technology with future].
Endomicroscopy becomes possible due to the integration of a miniaturized confocal microscope in the distal tip of a conventional endoscope. Endomicroscopy enables subsurface analysis of the gut mucosa and in vivo histology during ongoing endoscopy in full resolution by point scanning laser fluorescence analysis. Cellular, vascular and connective structures can be seen in detail. Graduation of cellular changes with endomicroscopy allows an immediate in-vivo diagnosis of different gastrointestinal diseases. The diagnostic spectrum of confocal endomicroscopy is currently expanding from screening and surveillance for colorectal cancer towards Barrett's esophagus, Helicobacter pylori associated gastritis and early gastric cancer. The new detailed images seen with confocal laser endomicroscopy are unequivocally the beginning of a new era where this optical development will allow a unique look on cellular structures and functions at and below the surface of the gut.
Biotechnology↗
Magnifying chromoendoscopy for the detection of premalignant gastrointestinal lesions.
The prognosis for patients with malignancies of the gastrointestinal tract is strictly dependent on the early detection of premalignant and malignant lesions. At present, endoscopy can be performed with new, powerful high-resolution or magnifying endoscopes. Comparable to the rapid development in chip technology, the optic features of the newly designed endoscopes offer resolutions that allow new mucosal surface details to be seen. In conjunction with chromoendoscopy, the newly discovered tool of video endoscopy is much easier to use and more impressive than previously used fibreoptic endoscopy. This review summarises the value of magnifying endoscopy in the upper and lower gastrointestinal tract and focuses on gastroesophageal reflux disease and early gastric and colorectal cancer.
Chromogenic Compounds↗
Acetic acid-guided biopsies after magnifying endoscopy compared with random biopsies in the detection of Barrett's esophagus: a prospective randomized trial with crossover design.
BACKGROUND: In contrast to standard video endoscopy, magnifying endoscopy after local acetic acid application enables recognition of mucosal surface architecture. OBJECTIVE: To investigate the diagnostic yield of magnifying endoscopy with acetic acid-targeted biopsies compared to random, 4-quadrant biopsies. DESIGN: Prospective randomized trial (ratio 1:1) with crossover design. SETTING: Two referral hospitals in Germany. PATIENTS: Thirty-one patients with Barrett's esophagus or visible columnar-lined lower esophagus. INTERVENTIONS: Patients were randomized to undergo either standard video endoscopy with 4-quadrant biopsies or magnifying endoscopy in conjunction with acetic acid application. All patients were re-examined 14 days after the initial endoscopy with the corresponding procedure. MAIN OUTCOME MEASUREMENTS: Primary outcome analysis (per protocol and per biopsy) was the histological proof of Barrett's epithelium. Secondary outcome analysis was the correlation between the surface architecture and the presence of Barrett's epithelium and the needed number of biopsies to confirm Barrett's epithelium for the 2 different procedures. RESULTS: Magnifying endoscopy enabled the prediction of Barrett's epithelium with a sensitivity of 100% and a specificity of 66%, respectively (accuracy 83.8%). Acetic acid-guided biopsies obtained a significantly higher percentage of tissues containing SCE (78%; 188/241) compared to random biopsies (57%; 159/280). LIMITATIONS: No data on the diagnosis of Barrett's dysplasia. CONCLUSION: Magnifying endoscopy with acetic acid-guided biopsies is superior to standard video endoscopy with random biopsies, and the number of biopsies needed to confirm Barrett's epithelium is half as much when compared to random biopsies.
Acetic Acid↗
The many roads to inflammatory bowel diseases.
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Animals↗
Colonoscopy, tumors, and inflammatory bowel disease - new diagnostic methods.
Accurate detection of premalignant lesions and early cancers in the colon is essential for curative endoscopic or surgical therapy, since the prognosis for the affected patients is closely related to the size and stage of the neoplastic lesion. Total colonoscopy is the accepted gold standard for screening and surveillance of colorectal cancer. This review summarizes recently published diagnostic developments and key findings in the areas of colonoscopy, colonic tumors, and inflammatory bowel diseases. Relevant findings have been reported for chromo-endoscopy in the diagnosis of colitis-associated neoplasia, as well as flat and depressed adenomas. Real-time Doppler capabilities have now been added to endoscopic optical coherence tomography; the results of large-scale testing of narrow-band imaging endoscopy in the colon are being awaited; and fluorescence imaging has recently been added to the facilities available in video endoscopy. Most importantly, endomicroscopy now for the first time allows single-cell subsurface imaging during ongoing colonoscopy procedures, opening the way to in-vivo molecular and functional imaging.
Colitis↗
[Giant bile duct stones in a patient with a 4-year remaining biliary stent].
We report on a 67-year-old female patient who presented in July 2005 with sudden onset of pain in the right upper abdomen. The patient had undergone cholecystectomy in 1987. Because of recurrent complaints in the right upper abdomen, a pigtail stent was placed into the common hepatic duct in 2001. When the patients presented now, the laboratory tests including liver enzymes were within normal ranges. Endoscopic retrograde cholangiography, however, revealed a remaining 10-French, impacted double pigtail endoprosthesis that was obstructed by sludge as well as multiple giant bile duct stones of 20 to 30 mm in size. The giant stones could be finally removed by the combined use of ESWL and endoscopic techniques. This case demonstrates that impacted stents may favour the development of giant bile duct stones that may result in clinical symptoms only after prolonged periods of time.
Aged↗
Confocal laser endomicroscopy: technical status and current indications.
Confocal laser endomicroscopy is a newly introduced endoscopic tool that makes it possible to carry out confocal microscopic examination of the mucosal layer during ongoing endoscopy. Different types of tissue and diseases can be diagnosed immediately, facilitating early diagnosis of gastrointestinal cancer. Analysis of the in vivo microarchitecture is helpful in targeting biopsies to relevant areas. In addition, subsurface imaging can unmask microscopic diseases - (microscopic colitis) or bacterial infection ( HELICOBACTER PYLORI), for example. Molecular imaging is becoming feasible, and this will shortly open the door to new indications in gastrointestinal endoscopy (e.g., in vivo receptor analysis).
Barrett Esophagus↗
In vivo diagnosis of collagenous colitis by confocal endomicroscopy.
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Aged↗
Novel signal transduction pathways: analysis of STAT-3 and Rac-1 signaling in inflammatory bowel disease.
Although the precise etiology of inflammatory bowel disease still remains unclear, considerable progress has been made in the identification of novel signal transduction pathways that elucidate the immunopathogenesis involved in the perpetuation of the inflammatory process. Augmented T cell resistance against apoptosis is regarded as a pivotal factor in the pathogenesis, as it impairs mucosal homeostasis and leads to unrestrained accumulation of activated T cells, which subsequently lead to the amplification of the inflammatory response. Therefore novel therapeutic strategies aim at restoring mucosal T cell susceptibility to apoptosis through targeting of signal transduction pathways that are elemental for augmented resistance of T lymphocytes against apoptosis. For example, a newly developed humanized anti-IL-6R monoclonal antibody that induces intestinal T cell apoptosis showed clinical efficacy in patients with active Crohn;s disease. Moreover, recent data that relate the immunosuppressive effects of azathioprine in inflammatory bowel disease to its apoptosis-inducing potential, have important implications for the design of a more specific therapeutic approach. The examination of these novel signal transduction pathways has elucidated the pathogenetic mechanisms involved in inflammatory bowel disease and gives hope for the development of new strategies that may result in a more effective and less toxic therapeutic procedure.
Apoptosis↗
Transforming growth factor beta induced FoxP3+ regulatory T cells suppress Th1 mediated experimental colitis.
BACKGROUND AND AIMS: The imbalance between effector and regulatory T cells plays a central role in the pathogenesis of inflammatory bowel diseases. In addition to the thymus, CD4+CD25+ regulatory T cells can be induced in the periphery from a population of CD25- T cells by treatment with transforming growth factor beta (TGF-beta). Here, we analysed the in vivo function of TGF-beta induced regulatory T (Ti-Treg) cells in experimental colitis. METHODS: Ti-Treg cells were generated in cell culture in the presence or absence of TGF-beta and tested for their regulatory potential in experimental colitis using the CD4+CD62L+ T cell transfer model. RESULTS: Ti-Treg cells significantly suppressed Th1 mediated colitis on CD4+CD62L+ T cell transfer in vivo, as shown by high resolution endoscopy, histology, immunohistochemistry, and cytokine analysis. Further analysis of in vivo and in vitro expanded Ti-Treg cells showed that exogenous interleukin 2 (IL-2) was crucial for survival and expansion of these cells. CONCLUSION: Our data suggest that regulatory Ti-Treg cells expand by TGF-beta and exogenous IL-2 derived from effector T cells at the site of inflammation. In addition to Tr1 and thymic CD4+CD25+ T cells, peripheral Ti-Treg cells emerge as a class of regulatory T cells with therapeutic potential in T cell mediated chronic intestinal inflammation.
Adoptive Transfer↗
IL-6 signaling promotes tumor growth in colorectal cancer.
Recent investigations support an important role for TGF-beta in the development of colorectal cancer. However, the molecular consequences of TGF-beta signaling in the colon remains incompletely understood. In a recent study in Immunity, we analyzed the role of TGF-beta in a murine model of colon cancer. Using transgenic mice overexpressing TGF-beta or a dominant negative TGF-beta receptor II under control of the CD2 minigene, we show that TGF-beta signaling in tumor infiltrating T lymphocytes regulates the growth of dysplastic colon epithelial cells, as determined by histology and a novel system for high resolution chromoendoscopy in vivo. At the molecular level, TGF-beta signaling in T cells regulated STAT-3 activation in tumor cells via IL-6. IL-6 signaling required tumor cell derived soluble IL-6R rather than membrane bound IL-6R and suppression of such TGF-beta-dependent IL-6 trans-signaling prevented tumor progression in vivo. Similar to these observations in mice, here we show that human colon cancer tissue expressed only low amounts of membrane bound IL-6R. In contrast, expression and activity of the matrix metalloproteinase TACE were increased. In summary, our data provide novel insights into the role of TGF-beta signaling in colorectal cancer and suggest novel therapeutic approaches for colorectal cancer based on an inhibition of TGF-beta-dependent IL-6 trans-signaling.
ADAM Proteins↗
Animal models of inflammatory bowel diseases.
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Animals↗
Endoscopic detection of early lower gastrointestinal cancer.
The prognosis for patients with malignancies of the lower gastrointestinal tract is strictly dependent on early detection of premalignant and malignant lesions. What should an ideal screening and surveillance colonoscopy be able to accomplish? The technique should allow detection of large but also discrete mucosal alterations. Ideally, endoscopic discrimination between neoplastic and non-neoplastic lesions would be possible during the ongoing procedure. At present, endoscopy can be performed with powerful new endoscopes. Comparable to the rapid development in chip technology, the optical features of the newly designed endoscopes offer resolutions, which allow new surface details to be seen. In conjunction with chromoendoscopy, the newly discovered tool video colonoscopy is much easier and more impressive today than with the previously used fibre-optic endoscopes. Recently, new endoscopic technologies such as narrow band imaging, endocytoscopy, or confocal laser endoscopy have allowed the discovery of a whole new world of image details which will surely improve the diagnostic yield in the field of early malignancies. This review summarises newly available technologies and clinical data about the diagnosis of early lower gastrointestinal cancers.
Colitis, Ulcerative↗
[Combined simulation training: a new concept and workshop is useful for crisis management in gastrointestinal endoscopy].
INTRODUCTION: Crisis management as well as realistic emergency situations can be trained in the new developed simulation workshop "Gastrointestinal Endoscopy and Crisis Resource Management" by combining a full-scale simulator and the Erlanger Endoscopy Trainer. The aim of the current study was to evaluate the efficiency of the newly developed simulation workshop. METHODS: Endoscopists with more than 12 months experience can train their endoscopic skills and crisis resource management with the help of different simulators. In addition, two different scenarios (GI bleeding with significant blood loss and sedation overdoses) embedded in a realistic surrounding (emergency room) have to be managed by the participants. Vital parameters, endoscopic skills, as well as personal interactions were recorded and graded. RESULTS: 100 participants took part in the newly developed workshop (between June and December 2003). The participants showed a significantly better endoscopic performance and a significantly better crisis management after the standardized training program. CONCLUSIONS: Simulation training plays an essential role in aviation and minimizes the risk for human errors. In the current study it is clearly shown that simulation training is also useful in gastrointestinal endoscopy. The newly developed workshop may thus be of crucial importance to improve personal crisis management. Simulation also leads to an improvement of endoscopic and emergency skills. Accordingly, simulation training should be recommended or offered as an education option in gastrointestinal endoscopy.
Computer-Assisted Instruction↗
In vivo imaging of colitis and colon cancer development in mice using high resolution chromoendoscopy.
BACKGROUND: Mouse models of colitis and cancer are indispensable for our understanding of the pathogenesis of these diseases. In the past, mice had to be sacrificed in order to analyse colitis activity and tumour development. We have developed a safe method for high resolution endoscopic monitoring of living mice. METHODS: Mice developing colitis or colonic tumours were anaesthetised using avertine and repeatedly examined by endoscopy. A novel miniendoscope (1.9 mm outer diameter), denoted Coloview, was introduced via the anus and the colon was carefully insufflated with an air pump before analysis of the colonic mucosa. An extra working channel allowed the introduction of biopsy forceps or injection needles as well as surface staining with methylene blue in order to visualise the surface of the crypts and the pit pattern architecture. RESULTS: Endoscopic pictures obtained were of high quality and allowed monitoring and grading of disease. Scoring of colitis activity as well as tumour size and growth was possible. In addition, pit pattern analysis using chromoendoscopy permitted discrimination between inflammatory and neoplastic changes. Biopsies yielded enough tissue for molecular and histopathological analyses. CONCLUSIONS: In summary, chromoendoscopy in mice allows monitoring of the development of colitis and colon cancer with high resolution. Manipulations such as local injection of reagents or taking biopsies can be performed easily.
Animals↗
Perspectives of chromo and magnifying endoscopy: how, how much, when, and whom should we stain?
The goal of every routine endoscopy in the gut is the early diagnosis of malignant and premalignant changes of the mucosa. Chromo- and magnifying endoscopes are exciting new tools and offer detailed analysis of the colonic mucosal surface and pit pattern architecture. This review summarizes recent advances in endoscopic characterization of colorectal lesions using magnification endoscopy and chromoendoscopy. Surface analysis of the colon using chromoendoscopy allows a prediction between non-neoplastic and neoplastic lesions with high specificity. The precise delineation of the borders and a more detailed macroscopic analysis of the lesions are further advantages. In particular, flat adenomas and early depressed cancers are now more frequently recognized in western countries suggesting that significant lesions were overlooked by conventional endoscopy in the past. Furthermore, chromoendoscopy can be used in a targeted fashion to screen for sporadic adenomas. Finally, in surveillance colonoscopy, patients with long-standing ulcerative colitis have a valuable benefit if targeted biopsies are performed to detect intraepithelial neoplasias after pan-chromoendoscopy with methylene blue. Although there is a long learning curve, chromoendoscopy should thus belong to every endoscopists armamentarium. However, detailed knowledge about the technique, dyes, and specific staining patterns are mandatory before the yield of screening or surveillance colonoscopy can be increased. The new detailed images seen with magnifying chromoendoscopy are unequivocally the beginning of a new era where new optical developments will allow a unique look on cellular structures.
Adenoma↗