Xiue Yan

The feasibility of light microscopic measurements of intercellular spaces in squamous epithelium in the lower-esophagus of GERD patients

The study aims to determine whether light microscopy can be used to accurately measure the diameters of intercellular spaces between squamous epithelial cells in the lower esophagus, and whether changes in this outcome measure can be used as a diagnostic marker for gastroesophageal reflux disease (GERD). The study has two parts. Part 1 involves 42 asymptomatic controls and 119 patients with typical symptoms of GERD, including 58 with erosive esophagitis (EE), and 61 patients with nonerosive gastroesophageal reflux disease (NERD). All biopsies were taken from the lower esophagus. All samples were observed using an immersion objective, after which diameters were measured by computer-assisted morphometry. Part 2 involves 61 individuals who were randomly selected from part 1, including 19 controls, 13 with NERD and 29 with EE. Diameter measurements using both light microscopy and transmission electron microscopy (TEM) were performed for samples of 61 individuals. Samples from a total of 61 individuals (31 male, 30 female, mean age 44.3 ± 16.0 years) were observed using both light microscopy and TEM. Both methods showed significant differences between control and disease groups; the outcomes from the two methods had a certain correlation (r = 0.605, P = 0.000). Morphometric analysis of all 161 individuals (83 males, 78 females, mean age 41.4 ± 15.7) showed mean diameters from light microscopy to be 0.58 ± 0.16 µm for controls, 1.07 ± 0.30 µm for NERD, and 1.29 ± 0.20 µm for EE; differences between control and disease groups were significant (P<0.05). The optimal cut-off value from receiver operator characteristic analysis was 0.85 µm. Diagnoses were validated using the combination of symptoms of GERD, endoscopy, and 24 h ambulatory pH monitoring as the gold standard. At the optimal cutoff, sensitivity was 93.3% and specificity was 100%. The diameters of the intercellular spaces in squamous epithelium of lower esophagus from controls and in patients with GERD can be quantitatively measured using light microscopy. Dilated diameters can serve as a sensitive, specific, and objective indicator for diagnosis of GERD.

Therapeutic Effect of Esophageal Foreign Body Extraction Management: Flexible versus Rigid Endoscopy in 216 Adults of Beijing

Background The aim of this study was to assess the effectiveness and complications of rigid endoscopy (RE) and flexible endoscopy (FE) for the extraction of esophageal foreign bodies (FB) in adults. Material/Methods A retrospective analysis was conducted on the medical records of 216 adult patients with esophageal FB impaction treated at Peking University Third Hospital, Beijing, China, between January 2008 and December 2012. Results The success rate of FB extraction was 100% (142/142) in patients treated with RE compared to 97.3% (72/74) in those treated with FE (P=0.045). The total incidence of complications in RE-treated patients was lower than that in FE-treated patients (28.2% vs. 45.9%, P=0.009), but the perforation rate was higher (5.6% vs. 1.4%, P=0.135). The incidences of total complications and perforation were associated with the duration of FB impaction in patients who underwent RE (both P<0.05) but not in patients who underwent FE. RE was more frequently used in extraction of FBs located in the upper esophagus (88.7%, 126/142) compared to FE (60.8%, 45/74) (P<0.05). The size of extracted FB was significantly larger in patients treated with FE compared to those treated with RE (P<0.05). Conclusions Both RE and FE were effective in the extraction of esophageal FB. However, the perforation rate and the need for general anesthesia were higher in RE-associated extraction. FE may be the preferred endoscopic treatment for the extraction of esophageal FB, except possibly for those impacted in the upper esophagus. FB extraction may produce better outcomes if endoscopy is employed early.

Effect of Helicobacter pylori eradication on reflux esophagitis therapy: a multi-center randomized control study.

Background:Helicobacter pylori (H. pylori) frequently colonizes the stomach. Gastroesophageal reflux disease (GERD) is a common and costly disease. But the relationship of H. pylori and GERD is still unclear. This study aimed to explore the effect of H. pylori and its eradication on reflux esophagitis therapy. Methods:Patients diagnosed with reflux esophagitis by endoscopy were enrolled; based on rapid urease test and Warth–Starry stain, they were divided into H. pylori positive and negative groups. H. pylori positive patients were randomly given H. pylori eradication treatment for 10 days, then esomeprazole 20 mg bid for 46 days. The other patients received esomeprazole 20 mg bid therapy for 8 weeks. After treatment, three patient groups were obtained: H. pylori positive eradicated, H. pylori positive uneradicated, and H. pylori negative. Before and after therapy, reflux symptoms were scored and compared. Healing rates were compared among groups. The &khgr;2 test and t-test were used, respectively, for enumeration and measurement data. Results:There were 176 H. pylori positive (with 92 eradication cases) and 180 negative cases. Healing rates in the H. pylori positive eradicated and H. pylori positive uneradicated groups reached 80.4% and 79.8% (P = 0.911), with reflux symptom scores of 0.22 and 0.14 (P = 0.588). Healing rates of esophagitis in the H. pylori positive uneradicated and H. pylori negative groups were, respectively, 79.8% and 82.2% (P = 0.848); reflux symptom scores were 0.14 and 0.21 (P = 0.546). Conclusions:Based on esomeprazole therapy, H. pylori infection and eradication have no significant effect on reflux esophagitis therapy.

Diagnostic value of dilated intercellular space and histopathologic scores in gastroesophageal reflux disease

The aim of this paper is to investigate the diagnostic value of histopathologic score and the dilated intercellular space (DIS) in patients with gastroesophageal reflux disease (GERD) and functional heartburn (FH). Participants with GERD symptoms including reflux esophagitis, non-erosive reflux disease (NERD), Barretts esophagus (BE), functional heartburn (FH), along with a control group with atypical GERD-like symptom (Sym-C), and asymptomatic healthy volunteers (H-C) were administered GERD questionnaire, and subjected to endoscopy and biopsies, as well as 24-hour pH-impedance monitoring. Biopsies were evaluated using standards from the 2011 Esohisto Project after Hematoxylin-Eosin staining. DIS was measured quantitatively under light microscopy. Among the total of 565 participants with qualified biopsy specimens, the mean DIS of the reflux esophagitis (RE) group was significantly wider compared with the other five groups. DIS in patients with GERD-like symptoms was significantly wider compared with the H-C. No significant differences were observed between NERD and FH. Results from 24-hour pH-impedance monitoring indicated that only the DIS of patients with acid reflux or the amount of acid reflux episodes in patients with DIS was significantly wider compared with patients with nonacid reflux or patients without DIS (P < 0.001). With DIS = 0.9 μm as the cutoff value, the sensitivity and specificity were 62.6% and 54.1%, respectively. Using the total histopathologic score > 3 as the diagnostic criterion, the sensitivity and specificity were 71.7% and 47.4%. DIS is closely associated with GERD and acid reflux. The diagnostic value of histological scores in lower esophagus in GERD is very similar to that of the quantitative measurement of DIS.

Tu1907 Curcumin Reduces the Inflammatory Factors of Reflux Esophagitis Through Non PKC Pathway in Part in Rat Model

Gastro-esophageal reflux disease complicated by Barretts esophagus (BE) is a major risk factor for esophageal adenocarcinoma (EA). The mechanisms whereby acid reflux may accelerate the progression from BE to EA are not fully understood. We have shown that NOX5-S was the major isoform of NADPH oxidase in FLO cells. NOX5-S mRNA expression is markedly increased in human Barretts mucosal biopsies with dysplasia and in EA tissues, suggesting that NOX5-S may play an important role in this progression. In this study we examined the signal-transduction pathway of acid-induced NOX5-S expression in FLO EA cells. Acid-induced increase in NOX5-S expression and H2O2 production was significantly decreased by knockdown of ROCK2 with ROCK2 siRNA and MEK1 with MEK1 siRNA, but not by knockdown of ROCK1 and MEK2. Conversely, overexpression of constitutively active ROCK2, but not constitutively active ROCK1, significantly enhanced NOX5-S expression and H2O2 production. In addition, acid treatment significantly increased the phosphorylation of MEK1 at threonine 292 (T292), but not at Serine 298 (S298). Overexpression of WT MEK1 and constitutively active MEK1 significantly increased NOX5-S promoter activity. Mutation of Threonine at 292 to Alanine abolished NOX5-S promoter activity and H2O2 production induced by overexpression of constitutively active MEK1. Acid-induced increase in ERK-2 phosphorylation was significantly reduced by Rho kinase inhibitor Y27632. Acidinduced increase in Rho kinase activity was not affected by knockdown of MEK1. In an in vitro kinase assay, we found that active ROCK2 increased MEK1 phosphorylation at T292. To test whether Rho kinases directly activate MEK1, we used synthesized peptides containing the flanking sequence of T292 and T292A in the ROCK2 kinase assay. We found that ROCK2 phosphorylated WT peptide DAAETPPRPRTPGRPLSSYGM, but did not phosphorylate T292A mutation peptide DAAETPPRPRAPGRPLSSYGM. Acid-induced increase in MEK1 T292 phosphorylation was significantly decreased by knockdown of ROCK2, but not of ROCK1. Overexpression of constitutively active ROCK2 remarkably increased MEK1 T292 phosphorylation, but not MEK1 S298 phosphorylation, in FLO EA cells. We conclude that acid-induced increase in NOX5-S expression and H2O2 production is mediated by sequential activation of ROCK2 and MEK1 in FLO EA cells. Activation of MEK1 depends on direct phosphorylation of MEK1 T292 by ROCK2. Supported by NIH NIDDK R01 DK080703.