Seon Mee Park

A new technique for gastric endoscopic submucosal dissection: peroral traction-assisted endoscopic submucosal dissection

BACKGROUND Compared with conventional EMR, endoscopic submucosal dissection (ESD) has a higher en bloc resection rate and complete resection rate, regardless of tumor size, in treating gastric neoplasms. However, ESD leads to more complications, such as bleeding or perforation, and, in particular, needs more procedure time than a conventional EMR. OBJECTIVE To report a new technique for ESD, peroral traction-assisted ESD with suture material, to perform easier and more rapid procedures in treating gastric neoplasms and to report the techniques early results. DESIGN A case series. SETTING A tertiary medical center. PATIENTS AND METHODS A total of 15 patients with gastric adenomas or early gastric cancers larger than 10 mm in diameter were consecutively enrolled. After marking around the periphery of the lesion, submucosal injection, followed by circumferential mucosal incision with a Flex-knife and an insulation-tipped knife, was conducted. After that, one hemostatic clip, tied by using a white silk suture, was applied at a site of the lesion suitable for oral traction. During submucosal dissection, the applied suture material was pulled to the oral side. Additional tractions were applied as needed. MAIN OUTCOME MEASUREMENTS En bloc resection rate, procedure time, complications. RESULTS All lesions were resected en bloc with free lateral and vertical margins by using this technique. The mean longest lesion size and specimen size were 18.1 mm (range 11-28 mm) and 43.7 mm in diameter (range 25-64 mm), respectively. The mean procedure time was 49.6 minutes (range 28-90 minutes). There was no significant bleeding that required blood transfusion or perforation related to the procedures. LIMITATIONS Single endoscopist, small patient number. CONCLUSION Peroral traction-assisted ESD with suture material is useful in treating gastric neoplasms located in various regions of the stomach. It may make ESD procedures easier, faster, and safer under better direct vision of the submucosal layer.

The prevalence of and risk factors for Barrett's esophagus in a Korean population: A nationwide multicenter prospective study.

Objective The aim of this study was to evaluate the prevalence of Barretts esophagus (BE) in the general Korean population by evaluating screening esophagogastroduodenoscopy. In addition, the risk factors for BE were identified. Method An esophagogastroduodenoscopy examination was performed in 25,536 subjects who had upper endoscopy screening from January 2006 to July 2006. Results Two hundred and fifteen subjects were confirmed to have BE by pathology, thus the prevalence of BE was calculated to be 0.84%. The endoscopic findings were subdivided into 2 groups: BE without reflux esophagitis (RE), which included 167 (77.7%), and BE with RE, which included 48 (22.3%). The analysis of symptoms showed that only 60.1% of the subjects with BE had reflux symptoms. Chest pain [odds ratio (OR): 1.48, 95% confidence interval (CI): 1.04-2.11] and epigastric soreness (OR: 1.42, 95% CI: 1.05-1.93) were found more frequently in the subjects with BE compared with the normal subjects. The multivariate analysis showed that the risk factors for all subjects with BE were a male sex (OR: 1.82, 95% CI: 1.32-2.50), nonsteroidal anti-inflammatory drug use (OR: 2.02, 95% CI: 1.28-3.20), hiatal hernia (OR: 5.66, 95% CI: 3.70-8.66), and an age ≥60 compared with an age <40 (OR: 1.81, 95% CI: 1.07-3.09). There was no significant difference associated with RE. Conclusions The prevalence of BE in Korean patients presenting for a routine health check-up was 0.84%, lower than reported in Western countries. Among the subjects with BE 77.7% did not have endoscopic erosions and there were no reflux symptoms in 39.9%. These results suggest that regular endoscopic screening with a high index of suspicion is necessary for the diagnosis of BE.

Is the addition of choleretic agents in multiple double-pigtail biliary stents effective for difficult common bile duct stones in elderly patients? A prospective, multicenter study

BACKGROUND Temporary biliary stenting is both technically easy and feasible, and choleretic agents such as ursodeoxycholic acid (UDCA) and a terpene preparation may promote a reduction in stone size. However, there are few comparative data on the effectiveness of choleretic agents available. OBJECTIVE To investigate the efficacy of multiple double-pigtail stents with or without UDCA and terpene on difficult common bile duct (CBD) stones. DESIGN A prospective, multicenter study. SETTING Four tertiary-care referral centers. PATIENTS This study involved 51 patients. INTERVENTION In total, 51 elderly patients with comorbidities who had difficult CBD stones refractory to conventional methods were randomized to receive either multiple 7F double-pigtail stents (group A) or stents in combination with UDCA and terpene (group B) for a period of 6 months. MAIN OUTCOME MEASUREMENTS Stone size reduction, successful duct clearance, and complications. RESULTS Complete endoscopic duct clearance was achieved in 14 patients (73.7%) in group A and 19 patients (86.4%) in group B (P = .826). The mean size of CBD stones (transverse/longitudinal diameter, mean ± SD) was 19.12 ± 4.48 mm/20.47 ± 3.86 mm in group A and 21.30 ± 7.08 mm/22.58 ± 7.61 mm in group B. Stone size decreased significantly to 12.04 ± 3.26 mm/13.31 ± 5.12 mm and 13.67 ± 5.40 mm/14.04 ± 6.12 mm, respectively (P < .01). However, there was no statistical difference in stone size reduction between the two groups (P = .685, P = .289). No serious complications related to the stent or endoscopic procedures were observed, except for cholangitis (n = 1, group A) and distal stent migration (n = 2, group B). LIMITATIONS Small number of patients in East Asia. CONCLUSION Temporary multiple double-pigtail biliary stenting was a safe and feasible method of treating difficult and large CBD stones in elderly patients and contributed to a reduction in stone size and successful duct clearance. However, the addition of choleretic agents did not result in a statistical difference in stone size or rate of successful duct clearance.

Combined aberrant expression of E-cadherin and S100A4, but not β-catenin is associated with disease-free survival and overall survival in colorectal cancer patients

Background/AimsEpithelial-to-mesenchymal transition (EMT) in cancers is related to metastasis, recurrence, and poor prognosis. We evaluated whether EMT-related proteins can act as prognostic biomarkers in colorectal cancer (CRC) patients.MethodsWe evaluated the expression of E-cadherin, β-catenin, and S100A4 by immunohistochemistry (IHC) in 333 CRC tissues from the tumor center and invasive margin. Tumor budding, cell grade, tumor stage, type of tumor growth, peritumoral lymphocyte infiltration (TLI), and perineural- or lymphovascular invasion were evaluated as pathological parameters. mRNA levels of E-cadherin, N-cadherin, β-catenin, and S100A4 from 68 specimens from the same set were analyzed by real time quantitative RT-PCR.ResultsLoss of E-cadherin, nuclear β-catenin, and gain of S100A4 were higher in the invasive margin than in the tumor center. Loss of E-cadherin was associated with cell grade, macroscopic type, perineural invasion, and tumor budding, β-catenin with microsatellite instability and tumor site, and S100A4 with growth type, macroscopic type, AJCC stage, lymphovascular invasion, and perineural invasion. The aberrant expression of E-cadherin and S100A4 not β-catenin in the invasive margin was a significant and independent risk factor for disease-free and overall-survival by multivariate analysis, along with AJCC stage and perineural invasion. mRNA levels of β-catenin and S100A4 were correlated with the IHC findings at the tumor invasive margin. E-cadherin and N-cadherin showed a weak inverse correlation.ConclusionsThe combination of loss of E-cadherin and gain of S100A4 in the tumor invasive margin can be used to stratify patients with the same AJCC stage into different survival groups.Virtual slidesThe virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9398289629244673

Helicobacter pylori-induced epithelial-mesenchymal transition, a potential role of gastric cancer initiation and an emergence of stem cells

We know little concerning the expression of transforming growth factor-β1 (TGF-β1) and TGF-β1-induced epithelial-mesenchymal transition (EMT) markers in gastric mucosa and their changes after eradication of Helicobacter pylori infection have not yet been clarified. In the present study, we compared the time course of messenger RNA (mRNA) expression of TGF-β1 and five EMT markers (Twist, Snail, Slug, vimentin and E-cadherin) in 111 controls, 55 patients with gastric dysplasia and 71 patients with early gastric cancer, following eradication of H.pylori. mRNA levels in non-cancerous gastric mucosa were measured using quantitative real time-polymerase chain reaction and the histologic findings of gastric mucosa were compared before and after eradication. The average duration of follow-up was 46.7 months (6.0-112.4). The levels of TGF-β1, Twist, Snail, Slug and vimentin mRNA, in addition to levels of CD44 detected by immunohistochemistry, showed all up-regulation in patients with dysplasia or early gastric cancer compared with controls (P < 0.05); moreover, the mRNA levels of E-cadherin, an epithelial marker, were decreased in these patients compared with the control group (P < 0.001). Eradication of H.pylori reduced the expression of TGF-β1, Twist, Snail, Slug and vimentin mRNA (P-value for slope <0.001), as well as the immunohistochemical expression of CD44 (P = 0.014), whereas it enhanced the expression of E-cadherin (P-value for slope < 0.05). Thus, H.pylori infection may trigger the TGF-β1-induced EMT pathway and the emergence of gastric cancer stem cells (CSCs). Its eradication may prevent the carcinogenesis of gastric cancer by inhibiting these two pathways.

Rescue endoscopic band ligation of iatrogenic gastric perforations following failed endoclip closure

Iatrogenic gastric perforation is one of the most serious complications during therapeutic endoscopy, despite significant advances in endoscopic techniques and devices. This case study evaluated the clinical efficacy and safety of the rescue endoscopic band ligation (EBL) technique in iatrogenic gastric wall perforation following the failure of primary endoclip closure. Five patients were enrolled in this study. These patients underwent emergency endoscopy following the onset of acute gastric wall perforation during endoscopic procedures. The outcome measurements were primary technical success and immediate or delayed procedure-related complications. Successful endoscopic closure using band ligation was reported in all patients, with no complication occurring. We conclude that EBL may be a feasible and safe alternate technique for the management of acute gastric perforation, especially in cases where closure is difficult with endoclips.

Phosphorylation of β-catenin at serine 663 regulates its transcriptional activity.

β-Catenin, a component of Wnt signaling, plays a key role in colorectal carcinogenesis. The phosphorylation status of β-catenin determines its fate and affects its cellular function, and serine 675 (S675) was previously identified as a common target of p21-activated kinase 1 (PAK1) and protein kinase A. In the present study, we explored the PAK1-specific phosphorylation site(s) in β-catenin. Active PAK1 T423E but not inactive PAK1 K299R interacted with and phosphorylated β-catenin. Mutagenesis followed by a kinase assay revealed that PAK1 phosphorylated S663 in addition to S675, and an anti-phospho-β-catenin(S663) antibody detected the phosphorylation of S663 downstream of PAK1 in various human colon cancer cells. Furthermore, the Wnt3a-stimulated S663 phosphorylation was inhibited by the PAK1-specific inhibitor, IPA-3, but not by H-89 or LY294002. The non-phosphorylatable mutant forms of β-catenin, S663A, S675A and S663/675A, showed similar defects in their PAK1-induced TCF/LEF transactivation, whereas the phosphomimetic form of β-catenin, S663D, demonstrated a transcriptional activity that was comparable to that of β-catenin S675D and β-catenin S663D/S675D. Taken together, these results provide evidence that PAK1 specifically phosphorylates β-catenin at S663 and that this phosphorylation is essential for the PAK1-mediated transcriptional activation of β-catenin.

Guilt, censure, and concealment of active smoking status among cancer patients and family members after diagnosis: a nationwide study

We aimed to identify the prevalence of feelings of guilt, censure, and concealment of smoking status among cancer patients and their family members who continued to smoke after the patients diagnosis.

Direct-Acting Antivirals for the Treatment of Chronic Hepatitis C: Open Issues and Future Perspectives

Currently, two direct-acting antivirals (DAAs) show well-established efficacy against hepatitis C virus (HCV), namely, first-wave protease inhibitors telaprevir and boceprevir. Most clinical trials have examined DAAs in combination with standard of care (SOC) regimens. Future therapeutic drugs were divided into three categories. They are second-wave protease inhibitors, second-generation protease inhibitors, and polymerase inhibitors. Second-wave protease inhibitors are more improved form and can be administered once a day. Oral drug combinations can be favored because interferon (IFN) not only has to be given as intradermal injection, but also can cause several serious side effects. Combination of drugs with different mechanisms shows a good sustained virological response (SVR). But several mutations are associated with viral resistance to DAAs. Therefore, genotypic resistance data may provide insights into strategies aimed at maximizing SVR rates and minimizing resistance. Combined drug regimens are necessary to prevent the emergence of drug-resistant HCV. Many promising DAA candidates have been identified. Of these, a triple regimen containing sofosbuvir shows promise, and treatment with daclatasvir plus asunaprevir yields a high SVR rate (95%). Oral drug combinations will be standard of care in the near future.

HDAC inhibitors induce epithelial-mesenchymal transition in colon carcinoma cells

The effects of histone deacetylase (HDAC) inhibitors on epithelial-mesenchymal transition (EMT) differ in various types of cancers. We investigated the EMT phenotype in four colon cancer cell lines when challenged with HDAC inhibitors trichostatin A (TSA) and valproic acid (VPA) with or without transforming growth factor-β1 (TGF-β1) treatment. Four colon cancer cell lines with different phenotypes in regards to tumorigenicity, microsatellite stability and DNA mutation were used. EMT phenotypes were assessed by the expression of E-cadherin and vimentin using western blot analysis, immunofluorescence, quantitative real-time RT-PCR following treatment with TSA (100 or 200 nM) or VPA (0.5 mM) with or without TGF-β1 (5 ng/ml) for 24 h. Biological EMT phenotypes were also evaluated by cell morphology, migration and invasion assays. TSA or VPA induced mesenchymal features in the colon carcinoma cells by a decrease in E-cadherin and an increase in vimentin expression at the mRNA and protein levels. Confocal microscopy revealed membranous attenuation or nuclear translocation of E-cadherin and enhanced expression of vimentin. These responses occurred after 6 h and increased until 24 h. Colon cancer cells changed from a round or rectangular shape to a spindle shape with increased migration and invasion ability following TSA or VPA treatment. The susceptibility to EMT changes induced by TSA or VPA was comparable in microsatellite stable (SW480 and HT29) and microsatellite unstable cells (DLD1 and HCT116). TSA or VPA induced a mesenchymal phenotype in the colon carcinoma cells and these effects were augmented in the presence of TGF-β1. HDAC inhibitors require careful caution before their application as new anticancer drugs for colon cancers.