Improvement of endocytoscopic findings after per oral endoscopic myotomy (POEM) in esophageal achalasia; does POEM reduce the risk of developing esophageal carcinoma? Per oral endoscopic myotomy, endocytoscopy and carcinogenesis

Background: Per oral endoscopic myotomy (POEM) has been reported to be a new therapeutic option for esophageal achalasia. The possibility that POEM could reduce the risk of developing esophageal squamous cell carcinoma was evaluated.Methods: This was a single-centre, retrospective study. Fifteen consecutive patients with esophageal achalasia who underwent POEM in our institution between August 2010 and January 2012 were enrolled. Ultra-high magnification with endocytoscopy was performed, and both histopathological and immunohistochemical evaluations for Ki-67 and p53 were assessed before and 3 months after POEM.Results: POEM was successfully performed and effectively released the dysphagia symptom in all patients without severe complications. Subjective symptoms (mean Ekcardt score, before 7.4 vs. after 0.5, p<0.05) and manometric pressure studies (mean lower esophageal sphincter pressure), before 82.7 vs. after 22.9 mmHg, p<0.05) showed substantial improvement following POEM. The average numbers of esophageal epithelial nuclei before and after POEM on endocytoscopic images were 128.0 and 78.0, respectively (p<0.05). The mean Ki-67-positive ratio was 26.0 (median 25.4, range, 10.3-33.2) before and 20.7 (median 20.0, 13.1-29.9; p=0.07) after POEM, and the mean p53-positive ratio was 2.35 (median 2.61, 0.32-4.23) before and 0.97 (median 1.49, 0.32-1.56; p<0.05) after POEM. A significant positive correlation was seen between the number of nuclei and the Ki-67-positive ratio (p<0.05).Conclusions: POEM appears to be an effective and less invasive treatment of choice against achalasia and may reduce the risk of esophageal carcinogenesis. Endocytoscopy can be useful for the assessment of esophageal cellular proliferation

Tumour necrosis factor-α converting enzyme (TACE) activity in human colonic epithelial cells1

Tumour necrosis factor (TNF)-α converting enzyme (TACE) releases biologically active, soluble TNF-α from transmembrane pro-TNF-α and has attracted interest as a specific therapeutic target in inflammatory bowel disease (IBD). Strong immunoreactivity for TACE protein was demonstrated recently in human colonic epithelium, but the function is unknown. We investigated if human colonic epithelial cells express functional TACE activity and how TACE expression is regulated in response to cytokine stimulation. TACE and TNF-α mRNA and protein expression were measured in HT-29 and DLD-1 colonic epithelial cells by reverse-transcription polymerase chain reaction, western blotting or enzyme-linked immunosorbent assay. Monocytic THP-1 cells served as positive control. Functional TACE activity was identified and quantified in detergent extracts of cell lines and freshly isolated colonocytes from 14 IBD patients and five controls by a hydrolysis assay using an oligopeptide spanning the cleavage site in pro-TNF-α. HT-29 and DLD-1 cells spontaneously expressed TACE mRNA and the active form of TACE protein at levels similar to those of monocytic cells. Functional TACE activity was demonstrated in all cell lines and in cells of controls or IBD patients irrespective of disease activity. TACE mRNA expression and functional activity remained unchanged in cell lines after stimulation with TNF-α despite clear induction of TNF-α mRNA expression and release of soluble TNF-α protein. The release of soluble TNF-α protein was almost completely abolished by CH4474, a synthetic TACE inhibitor. We conclude that functional TACE activity is constitutively expressed in human colonic epithelial cells and responsible for processing of the mature, soluble form of TNF-α in response to cytokine stimulation