Myelodysplastic Syndrome and Histone Deacetylase Inhibitors: “To Be or Not to Be Acetylated”?

Myelodysplastic syndrome (MDS) represents a heterogeneous group of diseases with clonal proliferation, bone marrow failure and increasing risk of transformation into an acute myeloid leukaemia. Structured guidelines are developed for selective therapy based on prognostic subgroups, age, and performance status. Although many driving forces of disease phenotype and biology are described, the complete and possibly interacting pathogenetic pathways still remain unclear. Epigenetic investigations of cancer and haematologic diseases like MDS give new insights into the pathogenesis of this complex disease. Modifications of DNA or histones via methylation or acetylation lead to gene silencing and altered physiology relevant for MDS. First clinical trials give evidence that patients with MDS could benefit from epigenetic treatment with, for example, DNA methyl transferase inhibitors (DNMTi) or histone deacetylase inhibitors (HDACi). Nevertheless, many issues of HDACi remain incompletely understood and pose clinical and translational challenges. In this paper, major aspects of MDS, MDS-associated epigenetics and the potential use of HDACi are discussed

Beyond white light:optical enhancement in conjunction with magnification colonoscopy for the assessment of mucosal healing in ulcerative colitis

Abstract Background and study aim The I-SCAN optical enhancement (OE) system with magnification is a recently introduced combination of optical and digital electronic virtual chromoendoscopy, which enhances mucosal and vascular details. The aim of this pilot study was to investigate the use of I-SCAN OE in the assessment of inflammatory changes in ulcerative colitis (UC). Patients and methods A total of 41 consecutive patients with UC and 9 control patients were examined by I-SCAN OE (Pentax Medical, Tokyo, Japan). Targeted biopsies of the imaged areas were obtained. A new optical enhancement score focusing on mucosal and vascular changes was developed. The diagnostic accuracy of I-SCAN OE was calculated against histology using two UC histological scores – Robarts Histopathology Index (RHI) and ECAP (Extent, Chronicity, Activity, Plus additional findings). Results The overall I-SCAN OE score correlated with ECAP (r = 0.70; P &lt; 0.001). The accuracy of the overall I-SCAN OE score to detect abnormalities by ECAP was 80 % (sensitivity 78 %, specificity 100 %). I-SCAN OE vascular and mucosal scores correlated with ECAP (r = 0.65 and 0.71, respectively; P &lt; 0.001). The correlation between overall I-SCAN OE score and RHI was r = 0.61 (P &lt; 0.01), and the accuracy to detect abnormalities by RHI was 68 % (sensitivity 78 %, specificity 50 %). The majority of patients with Mayo 0 had abnormalities on I-SCAN OE. Conclusion In UC, the new I-SCAN OE technology accurately identified mucosal inflammation, and correlated well with histological scores of chronic and acute changes.</jats:p

Endoscopic anterior fundoplication with the Medigus Ultrasonic Surgical Endostapler (MUSE™) for gastroesophageal reflux disease: 6-month results from a multi-center prospective trial

BACKGROUND: Both long-term proton pump inhibitor (PPI) use and surgical fundoplication have potential drawbacks as treatments for chronic gastroesophageal reflux disease (GERD). This multi-center, prospective study evaluated the clinical experiences of 69 patients who received an alternative treatment: endoscopic anterior fundoplication with a video- and ultrasound-guided transoral surgical stapler. METHODS: Patients with well-categorized GERD were enrolled at six international sites. Efficacy data was compared at baseline and at 6 months post-procedure. The primary endpoint was a ≥ 50 % improvement in GERD health-related quality of life (HRQL) score. Secondary endpoints were elimination or ≥ 50 % reduction in dose of PPI medication and reduction of total acid exposure on esophageal pH probe monitoring. A safety evaluation was performed at time 0 and weeks 1, 4, 12, and 6 months. RESULTS: 66 patients completed follow-up. Six months after the procedure, the GERD-HRQL score improved by >50 % off PPI in 73 % (48/66) of patients (95 % CI 60-83 %). Forty-two patients (64.6 %) were no longer using daily PPI medication. Of the 23 patients who continued to take PPI following the procedure, 13 (56.5 %) reported a ≥ 50 % reduction in dose. The mean percent of total time with esophageal pH <4.0 decreased from baseline to 6 months (P < 0.001). Common adverse events were peri-operative chest discomfort and sore throat. Two severe adverse events requiring intervention occurred in the first 24 subjects, no further esophageal injury or leaks were reported in the remaining 48 enrolled subjects. CONCLUSIONS: The initial 6-month data reported in this study demonstrate safety and efficacy of this endoscopic plication device. Early experience with the device necessitated procedure and device changes to improve safety, with improved results in the later portion of the study. Continued assessment of durability and safety are ongoing in a three-year follow-up study of this patient group

Confocal laser endomicroscopy is a new imaging modality for recognition of intramucosal bacteria in inflammatory bowel disease in vivo

Interaction of bacteria with the immune system within the intestinal mucosa plays a key role in the pathogenesis of inflammatory bowel disease (IBD). The aim of the current study was to develop a fluorescein-aided confocal laser endomicroscopy (CLE) method to visualise intramucosal enteric bacteria in vivo and to determine the involved mucosal area in the colon and ileum in patients with ulcerative colitis (UC) and Crohn's disease (CD)

Confocal endomicroscopy identifies loss of local barrier function in the duodenum of patients with Crohn's disease and ulcerative colitis

Background: Increased cell shedding with gap formation and local barrier dysfunction can be identified endomicroscopically in the terminal ileum of patients with inflammatory bowel disease. We aim to evaluate whether these changes are also present in the duodenum of patients with inflammatory bowel disease. Methods: Fifteen patients with Crohn's disease (CD), 10 patients with ulcerative colitis (UC), and 10 controls underwent fluorescein-aided confocal laser endomicroscopy (CLE). CLE was performed on macroscopically normal antral and duodenal (D1, D2, D3, D4) mucosa. Representative CLE images were prospectively analyzed. Images were scored for the number of epithelial gaps, cell shedding, and the degree of fluorescein leakage into the intestinal lumen. Results: Both CD and UC patients had significantly more epithelial gaps, epithelial cell shedding, and leakage of fluorescein into the duodenal lumen than controls. The degree of cell shedding and epithelial gap formation was similar in CD and UC patients. In all cases, macroscopic endoscopic appearances of the duodenum were normal, and conventional histological analysis showed a mild nonspecific duodenitis in 7 of 15 patients with CD. Patients with UC had a histologically normal duodenum. Gap formation, cell shedding, and fluorescein leakage was similar in CD with active compared with inactive disease, except for D2 shedding. Conclusions: CLE can detect epithelial damage and barrier loss in the duodenum of CD and UC patients that is not apparent on conventional endoscopy or histology. Copyright © 2014 Crohn's & Colitis Foundation of America, Inc

Endoscopic management of patients with high-risk colorectal colitis–associated neoplasia:a Delphi study

Background and Aims: Current guidelines recommend endoscopic resection of visible and endoscopically resectable colorectal colitis–associated neoplasia (CAN) in patients with inflammatory bowel disease (IBD). However, patients with high-risk CAN (HR-CAN) are often not amenable to conventional resection techniques, and a consensus approach for the endoscopic management of these lesions is presently lacking. This Delphi study aims to reach consensus among experts on the endoscopic management of these lesions. Methods: A 3-round modified Delphi process was conducted to reach consensus among worldwide IBD and/or endoscopy experts (n = 18) from 3 continents. Consensus was considered if ≥75% agreed or disagreed. Quality of evidence was assessed by the criteria of the Cochrane Collaboration group. Results: Consensus was reached on all statements (n = 14). Experts agreed on a definition for CAN and HR-CAN. Consensus was reached on the examination of the colon with enhanced endoscopic imaging before resection, the endoscopic resectability of an HR-CAN lesion, and endoscopic assessment and standard report of CAN lesions. In addition, experts agreed on type of resections of HR-CAN (20 mm, with or without good lifting), endoscopic success (technical success and outcomes), histologic assessment, and follow-up in HR-CAN. Conclusions: This is the first step in developing international consensus–based recommendations for endoscopic management of CAN and HR-CAN. Although the quality of available evidence was considered low, consensus was reached on several aspects of the management of CAN and HR-CAN. The present work and proposed standardization might benefit future studies