Dual-focus narrow band imaging for the detection of intestinal metaplasia and atrophic gastritis

Gastric cancer is one of the most common neoplastic diseases in developed Western countries, and is characterized by a poor prognosis when diagnosed at a late stage [1]. Atrophic gastritis and gastric intestinal metaplasia (GIM) are well-known risk factors for the development of gastric cancer. For this reason, endoscopy with multiple biopsies is recommended in patients with atrophic gastritis or GIM, to exclude preneoplastic or neoplastic tissue [1]. Magnifying endoscopy with narrow band imaging (NBI) has been shown to be reliable for in vivo diagnosis of atrophic gastritis and GIM [1] [2] [3] [4]. However, while magnifying endoscopy is routinely used by Asian endoscopists, it is not established in most European and Northern American endoscopy centers. Recently, a novel endoscope with NBI and dual-focus capability has been introduced to improve the quality of endoscopic imaging [5]. Dual focus allows the user to select between two focus settings by pushing a button on the scope. This results in an optimized close view of the tissue up to an 80-fold optical magnification. To the best of our knowledge, no reports exist so far on the use of this new technique for the detection and characterization of gastric lesions. We report a case in which dual-focus narrow band imaging was used to diagnose atrophic gastritis with intestinal metaplasia and obtain targeted biopsies in the same session

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

Phosphorothioate antisense oligonucleotides induce the formation of nuclear bodies

Antisense oligonucleotides are powerful tools for the in vivo regulation of gene expression. We have characterized the intracellular distribution of fluorescently tagged phosphorothioate oligodeoxynucleotides (PS-ONs) at high resolution under conditions in which PS-ONs have the potential to display antisense activity. Under these conditions PS-ONs predominantly localized to the cell nucleus where they accumulated in 20-30 bright spherical foci designated phosphorothioate bodies (PS bodies), which were set against a diffuse nucleoplasmic population excluding nucleoli. PS bodies are nuclear structures that formed in cells after PS-ON delivery by transfection agents or microinjection but were observed irrespectively of antisense activity or sequence. Ultrastructurally, PS bodies corresponded to electron-dense structures of 150-300 nm diameter and resembled nuclear bodies that were found with lower frequency in cells lacking PS-ONs. The environment of a living cell was required for the de novo formation of PS bodies, which occurred within minutes after the introduction of PS-ONs. PS bodies were stable entities that underwent noticeable reorganization only during mitosis. Upon exit from mitosis, PS bodies were assembled de novo from diffuse PS-ON pools in the daughter nuclei. In situ fractionation demonstrated an association of PS-ONs with the nuclear matrix. Taken together, our data provide evidence for the formation of a nuclear body in cells after introduction of phosphorothioate oligodeoxynucleotides

Management of Patients With Crohn's Disease and Ulcerative Colitis During the Coronavirus Disease-2019 Pandemic: Results of an International Meeting

The International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) is the only global organization devoted to the study of and management of the inflammatory bowel diseases (IBDs), namely, Crohn?s disease and ulcerative colitis. Membership is composed of physician-scientists who have established expertise in these diseases. The organization hosts an annual meeting and a number of working groups addressing issues of the epidemiology of IBD, diet and nutrition, and the development and use of treatments for IBD. There are currently 89 members of IOIBD representing 26 different countries. The organization has taken particular interest in the coronavirus disease-2019 (COVID-19) pandemic and how it may affect the IBD patient population. This document summarizes the results of 2 recent virtual meetings of the group and subsequent expert guidance for patients and providers

Screening and early diagnosis of colorectal cancer

Qu’est-on en droit d’attendre d’une méthode idéale de dépistage et de surveillance par coloscopie? La technique doit permettre la détection d’importantes lésions mais aussi de discrètes altérations muqueuses. Idéalement, la distinction endoscopique entre lésion néoplasique et non néoplasique devrait être possible en cours d’examen. Actuellement, l’endoscopie peut être réalisée avec de nouveaux endoscopes plus puissants. Parallèlement au développement rapide des puces électroniques, les caractéristiques optiques des nouveaux endoscopes offrent des résolutions qui permettent de voir de nouveaux détails de la surfacemuqueuse. En complément de la chromo-endoscopie, les nouveaux vidéocoloscopes permettent actuellement une observation plus aisée et plus impressionnante par rapport aux endoscopes à fibres optiques utilisés auparavant. Récemment, les nouvelles techniques endoscopiques, telles que l’imagerie à bande spectrale étroite (NBI), l’endocystocopie ou l’endoscopie laser confocale, ont permis de découvrir un nouvel univers grâce aux détails des images qui amélioreront sans aucun doute le rendement diagnostique dans le cadre des lésions malignes au début. La présente revue résume les techniques actuellement disponibles et les données cliniques qu’elles fournissent dans le diagnostic des cancers du tractus digestif inférieur au début

Advanced endoscopic imaging techniques in Crohn's disease

Background: Endoscopy is of pivotal importance in Crohn's disease (CD) patients for diagnosis, surveillance and assessment of disease activity and extent. Device-assisted enteroscopy (DAE) and small-bowel capsule endoscopy (SBCE) have recently changed our endoscopic approach to small-bowel imaging. Furthermore, new advanced endoscopic imaging techniques have been implemented into clinical practice to improve both characterization of mucosal inflammation and detection of dysplastic lesions. Aim: To provide readers with a review about the concept of advanced endoscopic imaging for the diagnosis and characterization of CD. Methods: A literature search on the use of advanced endoscopy techniques in IBD patients was performed. Results: DAE and SBCE allow for deep enteroscopy with high diagnostic yields and low complication's rate but their collocation in the diagnostic algorithm is still not clearly defined. Dye-based chromoendoscopy (DBC) and magnification chromoendoscopy improved dysplasia's detection in long standing colitis and prediction of inflammatory activity and extent. Dye-less chromoendoscopy (DLC) might offer the potential to replace conventional DBC for surveillance. However, both narrow band imaging and i-scan have already shown to significantly improve activity and extent assessment in comparison to white-light endoscopy. Confocal laser endomicroscopy (CLE) can detect more dysplastic lesions in surveillance colonoscopy and predict neoplastic and inflammatory changes with high accuracy compared to histology. Moreover, CLE-based molecular imaging may anticipate the therapeutic responses to biological therapy. Endocytoscopy can identify in vivo inflammatory mucosal cells harboring a new method to assess the mucosal activity. Conclusions: Recent progresses in small-bowel enteroscopy offer several potential benefits to improve both diagnosis and characterization of CD. New advanced endoscopic imaging techniques can improve detection of dysplasia and refine mucosal healing assessment, even looking beyond the morphological parameters revealed by conventional endoscopic imaging

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

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 prognosis. Nonetheless, no gold standard is available and the uncertainty of diagnosis may frequently lead to misclassification or repeated examinations. Hence, 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 strategies. Nowadays, the differential diagnosis is an untangled issue, and the proper diagnosis cannot be reached in up to 10% of patients presenting with IBD colitis. This topic is receiving emerging attention, as medical therapies, surgical approaches and leading prognostic outcomes require more and more disease-specific strategies in IBD patients. The optimization of standard diagnostic approaches based on clinical features, biomarkers, radiology, endoscopy and histopathology appears to provide only marginal benefits. Conversely, emerging diagnostic techniques in the field of gastrointestinal endoscopy, molecular pathology, genetics, epigenetics, metabolomics and proteomics have already shown promising results. Novel 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