Fluoroscopy-guided gastric peroral endoscopic pyloromyotomy (G-POEM): a more reliable and efficient method for treatment of refractory gastroparesis.

INTRODUCTION: Prior studies show promising results of the gastric peroral endoscopic pyloromyotomy (G-POEM) procedure for treatment of refractory gastroparesis. One major technical challenge involved in this procedure is identifying the pyloric muscular ring (PMR). The aim of this study is to establish a reliable method for identification of the PMR during G-POEM. METHODS: Fluoroscopy-guided G-POEM was performed by placing an endoclip at the 9 to 11'o clock position at the pylorus for identification of PMR. Conventional G-POEM was performed by observation of blue colored mucosa at the pylorus area as an indirect marker for PMR. The degree of the PMR identification was graded into well identified, identified, and not identified based on the appearance of the PMR. Procedure times were accurately documented. Gastroparesis cardinal symptoms index and gastric emptying scintigraphy were evaluated before and after the procedure. RESULTS: Fourteen patients were studied, seven underwent fluoroscopy-guided G-POEM, and seven patients underwent conventional G-POEM. All procedures achieved technical success and no adverse events occurred. In the seven patients who underwent fluoroscopy-guided G-POEM, the PMR was well identified in four patients and identified in three patients. In the seven patients who underwent conventional G-POEM, the PMR was identified in four patients and not identified in three patients. The average time to complete the fluoroscopy-guided G-POEM was significantly shorter than that of the conventional G-POEM. CONCLUSIONS: Fluoroscopy-guided G-POEM by placement of an endoclip at the pylorus was a reliable and safe method to direct the orientation of the submucosal tunnel, to facilitate the location of the PMR, and to shorten the procedure time.

Common polymorphisms of the microRNA genes (miR-146a and miR-196a-2) and gastric cancer risk: an updated meta-analysis.

The associations between two common polymorphisms in microRNA genes (miR-146a, dbSNP: rs2910164; miR-196a-2, dbSNP: rs11614913) and gastric cancer risk have frequently been examined; however, the results have often been controversial. This meta-analysis was performed to clarify the association between the two polymorphisms and gastric cancer risk. The literature search primarily utilized PubMed, Embase, SinoMed, and Wanfang databases to identify eligible studies. Odds ratios (ORs) with their 95% confidence intervals (CIs) were analyzed to investigate possible correlations. Subgroup analyses of ethnicity as well as source of controls were also performed. The correlation analysis was based on 11 studies, containing 4690 patients and 6066 controls for miR-146a (C>G) together with 1911 patients and 2484 controls for miR-196a-2 (T>C). For the miR-146a polymorphism, the values of the ORs and 95%CIs were >1, suggesting that a correlation exists. In subgroup analysis of source of controls, a correlation was also identified in the Asian subgroup. However, in Caucasians the ORs and 95%CIs were not distributed on the same side of the critical value 1, contra-indicative of a correlation in this group. For the miR-196a-2 polymorphism, the ORs with 95%CIs of both overall and subgroup analyses were also not restricted to >1 or ˂1. In summary, the results suggested that the miR-146a rs2910164 polymorphism was related to gastric cancer risk in Asians but not in Caucasians, and no distinct correlation seemed to exist between the miR-196a-2 rs11614913 polymorphism and the risk of gastric cancer.

Possible pathogenic role of T helper type 9 cells and interleukin (IL)-9 in atopic dermatitis.

T helper type 9 (Th9) cells are a novel identified subset of CD4(+) T helper cells, which could partly contribute to allergic inflammation, while the precise contribution of Th9 cells in atopic dermatitis (AD) remains unknown. We aimed to explore the possible role of Th9 cells in AD pathogenesis. The Th9 cell percentage, transcription factor PU.1 and cytokine interleukin (IL)-9 mRNA levels, as well as IL-9 serum concentration in peripheral circulation, were measured in AD patients, psoriasis patients and healthy controls. The Th9 cell percentage, PU.1 and IL-9 expression levels of AD patients were all increased significantly compared with the other two control groups (P < 0·01), and correlated positively with SCORing Atopic Dermatitis index, serum immunoglobulin (Ig)E and thymus- and activation-regulated chemokine (TARC) levels (P < 0·05). In simple AD patients and AD patients complicated by allergic rhinitis or asthma, there were no significant differences in the Th9 cell percentage, PU.1 and IL-9 expression levels between them. At the same time, IL-9 and vascular endothelial growth factor (VEGF) mRNA levels were detected in AD lesions and normal skin samples, which were both distinctly elevated in AD lesions, and there was a positive association between them (P < 0·01). Keratinocytes were cultured with IL-9 stimulation and the secretion of VEGF was detected. IL-9 can promote the secretion of VEGF by keratinocytes in a time- and dose-dependent manner. In conclusion, the expansion of the Th9 cell subset, up-regulation of the PU.1 transcription factor and increased secretion of the IL-9 cytokine may contribute to the pathogenesis of AD, which may be supported by the increased release of VEGF by keratinocyes after IL-9 stimulation.

Application of magnifying endoscopy with narrow-band imaging in diagnosing gastric lesions: a prospective study.

BACKGROUND: Magnifying endoscopy with narrow-band imaging (ME-NBI) can more clearly assess the surface pattern and microvascular architecture of gastric lesions. OBJECTIVE: To evaluate the diagnostic efficacy of ME-NBI in patients with early gastric cancer. DESIGN: Prospective study. SETTING: Single academic center. PATIENTS: This study involved 164 suspected gastric lesions in 146 consecutive patients who underwent ME-NBI for additional differential diagnosis before treatment. INTERVENTION: ME-NBI findings were classified into 3 groups based on irregularities, absence of surface pattern, and microvascular architecture. All lesions were treated endoscopically or surgically, and ME-NBI diagnosis was compared with histopathological findings. MAIN OUTCOME MEASUREMENTS: Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of real-time ME-NBI diagnosis were determined. RESULTS: The sensitivity, specificity, and accuracy of ME-NBI were 97.3%, 84.4%, and 90.2%, respectively, in distinguishing between cancerous and noncancerous lesions and were 92.3%, 89.7%, and 90.4%, respectively, in distinguishing undifferentiated from differentiated adenocarcinoma. ME-NBI accurately predicted depth of invasion in 37 of 39 differentiated adenocarcinomas (95%). LIMITATIONS: The sample size was relatively small. CONCLUSIONS: ME-NBI can successfully distinguish between cancerous and noncancerous lesions and between undifferentiated and differentiated adenocarcinomas. Of the 3 patterns on ME-NBI, type A is mainly characteristic of noncancerous lesions, type B is a good indicator of differentiated adenocarcinoma and intramucosal/superficially invasive cancers, and type C is indicative of undifferentiated adenocarcinoma or differentiated cancer with deep submucosal invasion.

A pilot study of endoscopic spray cryotherapy by pressurized carbon dioxide gas for Barrett's esophagus.

BACKGROUND AND STUDY AIMS: Endoscopic spray cryoablation is a novel approach for the treatment of Barrett's esophagus. However, few studies have reported its efficacy, especially with the use of carbon dioxide (CO (2)). The aim of the current study was to evaluate the short term efficacy and complications using CO (2) in endoscopic cryoablation of Barrett's esophagus. METHODS: Patients diagnosed with Barrett's esophagus underwent monthly stepwise cryoablation with pressurized CO (2) gas, with follow-up esophageal biopsies until complete histological reversal was achieved. Responses were analyzed with an intention-to-treat analysis according to complete response for intestinal metaplasia (CR-IM), which was defined as the elimination of all intestinal metaplasia including specialized intestinal metaplasia (SIM), subsquamous SIM, and dysplasia with intestinal metaplasia in the biopsies under narrow-band imaging (NBI). RESULTS: In total, 22 patients were enrolled, 20 of whom completed the treatment. Two patients declined further ablation after the first cryotherapy session. A total of 44 sessions were performed; a median of 2 sessions per patient (range 1 - 3 sessions) were needed to complete the ablation of Barrett's esophagus. No severe complications occurred. Follow-up endoscopies were performed in 20 patients (90.9 %). Two patients (9.1 %) were lost to follow-up. Median follow-up was 10 months (range 6 - 18 months). After cryotherapy, 20 patients (90.9 %) reached CR-IM of Barrett's esophagus. Patients underwent a median number of 3 follow-up endoscopies (range 2 - 4) with biopsies. At 6 months, recurrence was evident in three patients (13.6 % of the overall population, 15.0 % of the CR-IM population). One of the three patients developed intestinal metaplasia but no dysplastic change and the other two developed subsquamous SIM. CONCLUSIONS: The pressurized CO (2) spray cryotherapy is a relatively effective and safe endoscopic treatment for Barrett's esophagus.

Potent antitumoral efficacy of a novel replicative adenovirus CNHK300 targeting telomerase-positive cancer cells.

PURPOSE: Telomerase reverse transcriptase (hTERT) is the key determinant of telomerase activity and plays a crucial role in cellular immortalization and oncogenesis. It will be a promising target for cancer gene therapy. We constructed a novel replicative adenovirus CNHK300 in which hTERT promoter with three extra E-boxes downstream of the promoter was introduced and used to regulate adenoviral E1a gene, and studied its properties of selective replication in cancer cells and antitumoral activity. METHODS: Luciferase assay was used to detect hTERT promoter activity. The selective replication of CNHK300 in cancer cells was investigated by E1a Western blot and green fluorescent protein (GFP) reporter gene assay. The antitumoral activity of CNHK300 and its toxicity were measured on animal models. RESULTS: Luciferase assay showed that introducing extra E-boxes downstream of hTERT promoter is beneficial to decreasing the promoter activity in normal cells without affecting its strong activity in cancer cells. Experiments in vitro and in vivo demonstrated that CNHK300 can selectively target to hTERT-positive cancer cells and replicate in them, resulting in oncolytic or antitumoral effect. CNHK300 is superior to ONYX-015 in terms of selective replication and oncolytic or antitumoral effect. The toxicity assay showed no signs of toxicity to liver cells even at the higher dosage of CNHK300 in vivo. CONCLUSION: The hTERT promoter-controlled, replication-competent adenovirus CNHK300 is a promising system for targeted cancer gene therapy.

Nickel speciation and complexation kinetics in freshwater by ligand exchange and DPCSV.

A technique of ligand exchange with DMG (dimethylglyoxime) and DPCSV was applied to determine Ni speciation in lake, river, and groundwater samples. The working conditions related to ligand-exchange equilibrium were optimized, and the ligand-exchange kinetics were examined. The observed pseudo-first-order rate, kobsd, was about 3 x 10(-5) (s-1) for Ni(DMG)2 complex formation with an excess of DMG (microM) over Ni (nM) at pH 7.1-7.7. The second-order exchange kinetic constants, kexch, were between 1.2 x 10(2) and 5.7 x 10(3) s-1 M-1 for ligand exchange of NiEDTA with DMG and between 5 x 10(2) and 7 x 10(3) s-1 M-1 for exchange of natural ligands with DMG in the freshwater samples under similar conditions. Ni ligand exchange between natural ligands and DMG occurred over days with half-lifes of 5-95 h. Total dissolved Ni concentrations in samples from various freshwater systems in Switzerland ranged from 4 nM in an oligotrophic lake to 30 nM in a small river affected by inputs from sewage effluents and agriculture. Free ionic Ni2+ concentrations were determined in the range of 10(-13)-10(-15) M (pNi = 12.2-14.7), indicating that more than 99.9% of dissolved Ni was bound by organic ligands with strong affinity (log K 12.1-14.9) and low concentrations (13-100 nM) at pH 7.2-8.2. Because of slow ligand-exchange kinetics, Ni speciation in natural waters may in many cases not reach equilibrium.