ObjectivesThe Endocuff is a device mounted on the tip of the colonoscope to help flatten the colonic folds during withdrawal. This study aimed to compare the adenoma detection rates between Endocuff-assisted (EC) colonoscopy and standard colonoscopy (SC).MethodsThis randomized prospective multicenter trial was conducted at four academic endoscopy units in Germany. Participants: 500 patients (235 males, median age 64[IQR 54–73]) for colon adenoma detection purposes were included in the study. All patients were either allocated to EC or SC. The primary outcome measure was the determination of the adenoma detection rates (ADR).ResultsThe ADR significantly increased with the use of the Endocuff compared to standard colonoscopy (35.4%[95% confidence interval{CI} 29–41%] vs. 20.7%[95%CI 15–26%], p<0.0001). Significantly more sessile polyps were detected by EC. Overall procedure time and withdrawal time did not differ. Caecal and ileum intubation rates were similar. No major adverse events occurred in both groups. In multivariate analysis, age (odds ratio [OR] 1.03; 95%[CI] 1.01–1.05), male sex (OR 1.74; 95%CI 1.10–2.73), withdrawal time (OR 1.16; 95%CI 1.05–1.30), procedure time (OR 1.07; 95%CI 1.04–1.10), colon cleanliness (OR 0.60; 95%CI 0.39–0.94) and use of Endocuff (OR 2.09; 95%CI 1.34–3.27) were independent predictors of adenoma detection rates.ConclusionsEC increases the adenoma detection rate by 14.7%(95%CI 6.9–22.5%). EC is safe, effective, easy to handle and might reduce colorectal interval carcinomas.Trial RegistrationClinicalTrials.gov NCT02034929.
Background & Aims:
Induction of immediate early transcription factors (ITF) represents the first transcriptional program controlling mitogen stimulated cell cycle progression in cancer. Here, we examined the transcriptional mechanisms regulating the ITF protein c-Myc and its role in pancreatic cancer growth in vitro and in vivo.
Methods:
Expression of ITF proteins were examined by RT-PCR and immunoblotting, and their implications in cell cycle progression and growth were determined by flow cytometry and [3H] thymidine incorporation. Intracellular Ca2+ concentrations, calcineurin activity and cellular NFAT distribution were analyzed. Transcription factor complex formations and promoter regulation were examined by immunoprecipitations, reporter gene assays and chromatin immunoprecipitation (ChIP). Using a combination of RNAi knockdown technology and xenograft models we analyzed the significance for pancreatic cancer tumor growth.
Results:
Serum promotes pancreatic cancer growth through induction of the proproliferative NFAT-c-Myc axis. Mechanistically, serum increases intracellular Ca2+ concentrations and activates the calcineurin/NFAT pathway to induce c-Myc transcription. NFAT binds to a serum responsive element within the proximal promoter, initiates p300-dependent histone acetylation and creates a local chromatin structure permissive for the inducible recruitment of ELK-1, a protein required for maximal activation of the c-Myc promoter. The functional significance of this novel pathway was emphasized by impaired c-Myc expression, G1-arrest and reduced tumor growth upon NFAT depletion in vitro and in vivo.
Conclusion:
Our study uncovers a novel mechanism regulating cell growth and identifies the NFAT-ELK complex as modulators of early stages of mitogen stimulated proliferation in pancreatic cancer cells.
Prehospital chest emergency sonography trial is a novel prehospital ultrasound algorithm for patients with dyspnea. Pleural effusion may serve as a novel prehospital marker for patients with decompensated CHF, thus facilitating the often difficult differential diagnosis between CHF and COPD.
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