Advanced endoscopic imaging for diagnosis of inflammatory bowel diseases : present and future perspectives

Crohn's disease and ulcerative colitis are chronic inflammatory bowel diseases (IBD) causing severe damage of the luminal gastrointestinal tract. Differential diagnosis between both disease entities is sometimes awkward requiring a multifactorial pathway, including clinical and laboratory data, radiological findings, histopathology and endoscopy. Apart from disease diagnosis, endoscopy in IBD plays a major role in prediction of disease severity and extent (i.e. mucosal healing) for tailored patient management and for screening of colitis-associated cancer and its precursor lesions. In this state-of-the-art review, we focus on current applications of endoscopy for diagnosis and surveillance of IBD. Moreover, we will discuss the latest guidelines on surveillance and provide an overview of the most recent developments in the field of endoscopic imaging and IBD

Feasibility trial of the newly introduced optical enhancement technology in patients with gastroesophageal reflux disease

BACKGROUND: Optical Enhancement technology (OE) combines bandwidth-limited light and image enhancement processing technology to enhance subtle mucosal and vascular details. This is the first study assessing the new technology for the diagnosis of gastroesophageal reflux disease (GERD). PATIENTS AND METHODS: Consecutive patients with GERD and controls were prospectively included. The distal esophagus was examined in all quadrants with high definition white-light endoscopy (HD-WLE) followed by OE and biopsies for histopathological analysis. Features observed only by OE were compared between controls and patients with GERD. RESULTS: A total of 100 areas were evaluated. About 56% of patients had a diagnosis of GERD. The mean age of patients was 53 years (range 27-89 years), 60% were female. Compared to controls, patients with diagnosis of GERD showed significantly more often tortuosity (p = 0.042), dilation (p = 0.0003), and increased number (p = 0.001) of intrapapillary capillary loops (IPCLs). In addition, increased vascularity and mucosal breaks were significantly more often found in patients with GERD as compared to controls (p < 0.05). On multivariate analysis, increased number and dilation of IPCL were the best predictors of GERD. CONCLUSIONS: The newly introduced OE technology significantly improves the diagnosis of GERD compared to HD-WLE. The results should be confirmed in a multicenter trial

Leaving colorectal polyps in place can be achieved with high accuracy using blue light imaging (BLI)

Objectives: A negative predictive value of more than 90% is proposed by the American Society of Gastrointestinal Endoscopy Preservation and Incorporation of Valuable Endoscopic Innovations (PIVI) statement for a new technology in order to leave distal diminutive colorectal polyps in place without resection. To our knowledge, no prior prospective study has yet evaluated the feasibility of the most recently introduced blue light imaging (BLI) system for real-time endoscopic prediction of polyp histology for the specific endpoint of leaving hyperplastic polyps in place. Aims: Prospective assessment of real-time prediction of colorectal polyps by using BLI. Material and methods: In total, 177 consecutive patients undergoing screening or surveillance colonoscopy were included. Colorectal polyps were evaluated in real-time by using high-definition endoscopy and the BLI technology without optical magnification. Before resection, the endoscopist described each polyp according to size, shape and surface characteristics (pit and vascular pattern, colour and depression), and histology was predicted with a level of confidence (high or low). Results: Histology was predicted with high confidence in 92.5% of polyps. Sensitivity of BLI for prediction of adenomatous histology was 92.68%, with a specificity and accuracy of 94.87 and 93.75%, respectively. Following the recommendation of the PIVI statement, positive and negative predictive values were calculated with values of 95 and 92.5%, respectively. Prediction of surveillance based on both US and European guidelines was correctly predicted in 91% of patients. Conclusion: The most recently introduced BLI technology is accurate enough to leave distal colorectal polyps in place without resection. BLI also allowed for assignment of postpolypectomy surveillance intervals. This approach therefore has the potential to reduce costs and risks associated with the redundant removal of diminutive colorectal polyps

The transcription factor NFATc2 controls IL-6-dependent T cell activation in experimental colitis.

The nuclear factor of activated T cells (NFAT) family of transcription factors controls calcium signaling in T lymphocytes. In this study, we have identified a crucial regulatory role of the transcription factor NFATc2 in T cell-dependent experimental colitis. Similar to ulcerative colitis in humans, the expression of NFATc2 was up-regulated in oxazolone-induced chronic intestinal inflammation. Furthermore, NFATc2 deficiency suppressed colitis induced by oxazolone administration. This finding was associated with enhanced T cell apoptosis in the lamina propria and strikingly reduced production of IL-6, -13, and -17 by mucosal T lymphocytes. Further studies using knockout mice showed that IL-6, rather than IL-23 and -17, are essential for oxazolone colitis induction. Administration of hyper-IL-6 blocked the protective effects of NFATc2 deficiency in experimental colitis, suggesting that IL-6 signal transduction plays a major pathogenic role in vivo. Finally, adoptive transfer of IL-6 and wild-type T cells demonstrated that oxazolone colitis is critically dependent on IL-6 production by T cells. Collectively, these results define a unique regulatory role for NFATc2 in colitis by controlling mucosal T cell activation in an IL-6-dependent manner. NFATc2 in T cells thus emerges as a potentially new therapeutic target for inflammatory bowel diseases

The Transcription Factor T-bet Regulates Mucosal T Cell Activation in Experimental Colitis and Crohn's Disease

The balance between pro and antiinflammatory cytokines secreted by T cells regulates both the initiation and perpetuation of inflammatory bowel diseases (IBD). In particular, the balance between interferon (IFN)-γ/interleukin (IL)-4 and transforming growth factor (TGF)-β activity controls chronic intestinal inflammation. However, the molecular pathways that evoke these responses are not well understood. Here, we describe a critical role for the transcription factor T-bet in controlling the mucosal cytokine balance and clinical disease. We studied the expression and function of T-bet in patients with IBD and in mucosal T cells in various T helper (Th)1- and Th2-mediated animal models of chronic intestinal inflammation by taking advantage of mice that lack T-bet and retroviral transduction techniques, respectively. Whereas retroviral transduction of T-bet in CD62L+ CD4+ T cells exacerbated colitis in reconstituted SCID mice, T-bet–deficient T cells failed to induce colitis in adoptive transfer experiments suggesting that overexpression of T-bet is essential and sufficient to promote Th1-mediated colitis in vivo. Furthermore, T-bet–deficient CD62L− CD4+ T cells showed enhanced protective functions in Th1-mediated colitis and exhibited increased TGF-β signaling suggesting that a T-bet driven pathway of T cell activation controls the intestinal balance between IFN-γ/IL-4 and TGF-β responses and the development of chronic intestinal inflammation in T cell–mediated colitis. Furthermore, TGF-β was found to suppress T-bet expression suggesting a reciprocal relationship between TGF-β and T-bet in mucosal T cells. In summary, our data suggest a key regulatory role of T-bet in the pathogenesis of T cell–mediated colitis. Specific targeting of this pathway may be a promising novel approach for the treatment of patients with Crohn's disease and other autoimmune diseases mediated by Th1 T lymphocytes

Hepatitis B-Verbund. Etablierung eines in vitro-Systems zum effizienten Mutantenscreening Schlussbericht

Using adult primary human hepatocytes we have established an in vitro system for the study of infectivity and replication of HBV. The aim of the current study was the development of an assay system for quick and sensitive demonstration of HBV infection to be used for analysis of infectivity of mutant HBV. For this purpose a modified PCR protocol was used by means of which the inoculating RC DNA can be distinguished from the CCC DNA, which appears as first replicative intermediate during the course of infection. Using this technique we could reduce the amount of required cells and shorten the time in tissue culture required for infection experiments to 2 to 3 days, which will enable us to do a quantitative screening of HBV mutants in the frame of this cooperative program. We have used this technique to demonstrate (i) that myristylation of the large surface protein is required for HBV infectivity, (ii) that HBV is unlikely to replicate in human peripheral blood mononuclear cells, (iii) that HBV is taken up in a pH independent manner. (orig.)SIGLEAvailable from TIB Hannover: DtF QN1(81,8) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung und Forschung (BMBF), Bonn (Germany)DEGerman

Cutting edge: TGF-beta induces a regulatory phenotype in CD4(+)CD25(-) T cells through Foxp3 induction and down-regulation of Smad7

CD4(+) CD25(+) regulatory cells are a subpopulation of T lymphoiytes of thymic origin. However, recent data suggest an alternative commitment of regulatory T cells in the periphery, although the precise mechanism is unknown. In the present work, we demonstrate that TGF-beta is able to induce Toxp3 expression and subsequently a regulatory phenotype in CD4(+) CD25(-) peripheral murine T cells. Similarly, TGF-beta induced Foxp3 in human CD4(+) CD25(-) T cells. Moreover, we show that the inhibitory Smad7 protein that is normally induced by TGF-9 and limits TGF-beta signaling, is strongly down-regulated by Foxp3 at the transcriptional level. Foxy3-mediated down-regulation of Smad7 subsequently rendered CD4+ CD25- T cells highly susceptible to the morphogenic and regulatory effects of TGF-beta signaling via Smad3/4. In summary, we demonstrate that TGF-beta induces a regulatory phenotype in CD4(+) CD25(-) T cells through the induction of Toxp3 and a positive autoregulatory loop of TGF-beta signaling due to the absence of Smad7

Evaluation of a novel colonoscope offering flexibility adjuster - a retrospective observational study

BACKGROUND: Although colonoscopy is the gold standard for colorectal cancer screening, colonic looping may make complete colonoscopy challenging. Commonly available stiffening device colonoscopy has been described as helpful but not effective enough to prevent looping. In this context the effect on cecal intubation time and rate was described differently in various studies and in some studies had no impact on cecal intubation time at all. The aim of this study was to evaluate whether a novel colonoscope with gradual stiffness (Fujifilm EC760R-V/I- flexibility adjuster, Tokyo, Japan) using four significantly different grades of stiffness can be an alternative to established devices in terms of loop prevention, cecal intubation rate and time, adverse events, and patient/examiner satisfaction. METHODS: Consecutive patients without previous colorectal surgery were analyzed retrospectively. Colonoscopy was performed with the new colonoscope and performance characteristics, including time to cecum, withdrawal time, total examination time, and patient and endoscopist satisfaction were recorded. RESULTS: Among 180 consecutive procedures, 98.3% of examinations were complete to the cecum. The endoscopic flexibility adjuster was used in 150 of 180 cases (83.3%). Overall, the device was scored by the examiner as helpful to prevent looping in 146 of the 150 cases (97.7%). Mean cecal intubation time was 6.5 min, with 35% of examination performed in under 5 min with a mean withdrawal time of 7 min. Mean total examination time was 18 min. Patient satisfaction was rated as high in all examinations performed. CONCLUSION: The new flexibility adjuster colonoscope was shown to be helpful in loop prevention, allowed for fast and successful cecal intubation, and led to a high rate of patients satisfaction