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Reprocessing of gastrointestinal (GI) endoscopes and accessories is an essential part of patient safety and quality control in GI endoscopy centers. However, current endoscopic reprocessing guidelines or procedures are not adequate to ensure patient-safe endoscopy. Approximately 5.4 % of the clinically used duodenoscopes remain contaminated with high-concern microorganisms. Thus, the Digestive Endoscopy Society of Taiwan (DEST) sets standards for the reprocessing of GI endoscopes and accessories in endoscopy centers. DEST organized a task force working group using the guideline-revision process. These guidelines contain principles and instructions of step-by-step for endoscope reprocessing. The updated guidelines were established after a thorough review of the existing global and local guidelines, systematic reviews, and health technology assessments of clinical effectiveness. This guideline aims to provide detailed recommendations for endoscope reprocessing to ensure adequate quality control in endoscopy centers., Competing Interests: Conflicts of interest All authors declare that they have no relevant conflicts of interest related to this article., (Copyright © 2023. Published by Elsevier B.V.)

Microalgae extracts have shown antitumor activities. However, the antitumor mechanism of them is not yet completely clear, especially the effect on cancer stem cells (CSCs). This study aimed to elucidate the antitumor activity and mechanism of microalgal extract from thermotolerant Coelastrella sp. F50 (F50) in hepatocellular carcinoma (HCC). Oncogenic behaviors were analyzed using cell proliferation, colony formation, invasion, sphere formation, and side population cells (SPCs) assays in HCC cells after F50 treatment. The molecular mechanism was further studied by quantitative real-time PCR, immunoblot, and immunofluorescence analyses. The chemopreventive efficacy of F50 was evaluated in rat orthotopic hepatoma, and the hepatic pathologies were investigated by immunohistochemical, immunoblot, and immunofluorescence analyses. F50 specifically suppressed hepatic CSCs (tumor spheres, drug efflux, CD133/ABCG2 CSCs markers) with no cytotoxicity in vitro. In the animal experiments, prophylactic F50 administration significantly attenuated tumor progression and improved liver function in HCC-bearing rats. In the mechanistic analysis, F50 potentially inhibited cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE 2 ) axis in HCC cells and rat hepatoma, and exogenous PGE 2 restored CSCs properties in F50-treated HCC cells. In summary, F50 extract inhibits hepatic CSCs by COX-2/PGE 2 downregulation and may facilitate a novel phytotherapy for HCC prevention., (© 2021 John Wiley & Sons, Ltd.)

Hepatitis is an important health problem worldwide. Novel molecular targets are in demand for detection and management of hepatitis. Hepatoma-derived growth factor (HDGF) has been delineated to participate in hepatic fibrosis and liver carcinogenesis. However, the relationship between hepatitis and HDGF remains unclear. This study aimed to elucidate the role of HDGF during hepatitis using concanavalin A (ConA)-induced hepatitis model. In cultured hepatocytes, ConA treatment-elicited HDGF upregulation at transcriptional level and promoted HDGF secretion while reducing intracellular HDGF protein level and cellular viability. Similarly, mice receiving ConA administration exhibited reduced hepatic HDGF expression and elevated circulating HDGF level, which was positively correlated with serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. By using HDGF knockout (KO) mice, it was found the ConA-evoked cell death was prominently alleviated in KO compared with control. Besides, it was delineated HDGF ablation conferred protection by suppressing the ConA-induced neutrophils recruitment in livers. Above all, the ConA-mediated activation of tumor necrosis factor-α (TNF-α)/interleukin-1β (IL-1β)/interleukin-6 (IL-6)/cyclooxygenase-2 (COX-2) inflammatory signaling was significantly abrogated in KO mice. Treatment with recombinant HDGF (rHDGF) dose-dependently stimulated the expression of TNF-α/IL-1β/IL-6/COX-2 in hepatocytes, further supporting the pro-inflammatory function of HDGF. Finally, application of HDGF antibody not only attenuated the ConA-mediated inflammatory cascade in hepatocytes, but also ameliorated the ConA-induced hepatic necrosis and AST elevation in mice. In summary, HDGF participates in ConA-induced hepatitis via neutrophils recruitment and may constitute a therapeutic target for acute hepatitis., (© 2020 Federation of American Societies for Experimental Biology.)

Epirubicin is a chemotherapy agent for hepatocellular carcinoma (HCC). However, the outcome of HCC patients receiving epirubicin remains unsatisfactory. Moreover, our previous study indicated that celecoxib suppresses HCC progression and liver cancer stemness. This study evaluated the potential of celecoxib to serve as a complementary therapy during epirubicin treatment. Cell proliferation, apoptosis, invasiveness, and anchorage-independent growth were analyzed in hepatoma cells. Therapeutic efficacy was validated in rat orthotopic Novikoff hepatoma. After animal sacrifice, the antitumor mechanism of celecoxib and epirubicin combined therapy was investigated by histological analysis. Celecoxib enhanced the cytotoxic activity of epirubicin in HCC cells by promoting apoptosis. Besides, celecoxib potentiated the antineoplastic function of epirubicin in inhibiting the invasiveness and anchorage-independent growth of HCC cells. Ultrasound monitoring showed that combined therapy was more potent than either therapy alone in perturbing HCC progression. Consistently, the size and weight of dissected HCC tissues from rats receiving combined therapy were smallest among all groups. HCC treated with combined therapy exhibited the highest prevalence of apoptotic cells, which was accompanied by reduced proliferating and angiogenic activities in tumor tissues. Moreover, the expression levels of cancer stemness markers (CD44 and CD133) and drug transporter MDR-1 were significantly diminished in rats receiving combined therapy. Besides, celecoxib treatment increased the infiltration of cytotoxic T lymphocytes (CTLs) and reduced the number of regulatory T cells (Tregs), tumor-associated macrophages (TAMs), and the expression of immune checkpoint PD-L1 in HCC tissues during epirubicin therapy. Celecoxib augmented the therapeutic efficacy while modulated cancer stemness and antitumor immunity. Thus, celecoxib may serve as complementary therapy to improve the outcome of patients with advanced HCC during epirubicin treatment., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Whether preserving sphincter of Oddi (SO) function by endoscopic papillary balloon dilation (EPBD) is beneficial for preventing recurrent common bile duct stone disease (CBDS) is controversial. The aim of this study was to measure sphincter of Oddi (SO) function by using SO manometry, and to evaluate the association with recurrent CBDS., Methods: Patients with suspected CBDS who underwent successful EPBD were included. These patients underwent SO manometry at two months after EPBD with bile duct clearance. They were regularly followed for recurrent CBDS., Results: From January 2000 to December 2009, 185 patients received EPBD and SO manometry was included. There were 64% male with mean age of 65 ± 15.6 years. Mean ballooning inflation size was 1.1 ± 0.19 cm and mean ballooning time was 4.5 ± 0.85 min 55.7% had a sphincter of Oddi basal pressure (SOBP) of 0 mmHg, 16.2% < 10 mmHg, 26.5% 10-40 mmHg, and 1.6% > 40 mmHg. In multivariate analysis, EPBD with balloon ≥1.2 cm was the only factor for loss of SO function. Moreover, patients with preserved SO function had higher stone recurrence rate (15% vs. 5%, p = 0.034)., Conclusion: EPBD using balloon ≥1.2 cm is a major factor for loss of SO function, which seems to reduce the risk of recurrent CBD stones., (Copyright © 2018 the Chinese Medical Association. Published by Elsevier Taiwan LLC. All rights reserved.)

Background: In patients with common bile duct stones (CBDS) and intact gallbladder, further management for the gallbladder after the CBDS clearance is still controversial. The relationship between gallbladder motility and the biliary complications were seldom discussed. Our study is to predict the subsequent biliary complications by gallbladder function test using fatty meal sonography (FMS) in patients with CBDS who had been treated by endoscopic retrograde cholangiopancreatography (ERCP)., Methods: Patients with an intact gallbladder and CBDS after endoscopic clearance of bile duct were enrolled. Patients received a fatty meal sonography after liver function returned to normal. The fasting volume, residual volume, and gallbladder ejection fraction (GBEF) in FMS were measured. Relationships of patients' characteristics, gallbladder function and recurrent biliary complication were analyzed., Results: From 2011 to 2014, 118 patients were enrolled; 86 patients had calculus gallbladders, and 32 patients had acalculous gallbladders. After a mean follow- up of 33 months, 23 patients had recurrent biliary complications. Among 86 patients with calculus gallbladder, 15 patients had spontaneous clearance of gallbladder stones; 14 patients received cholecystectomy due to acute cholecystitis or recurrent colic pain with smooth postoperative courses. In the follow up period, six patients died of non-biliary causes. The GBEF is significant reduced in most patients with a calculus gallbladder in spite of stone color. Calculus gallbladder, alcohol drinking and more than one sessions of initial endoscopic treatment were found to be the risk factors of recurrent biliary complication., Conclusions: Gallbladder motility function was poorer in patients with a calculus gallbladder, but it cannot predict the recurrent biliary complication. Since spontaneous clearance of gallbladder stone may occur, wait and see policy of gallbladder management after endoscopic treatment of CBDS is appropriate, but regular follow- up in those patients with risk factors for recurrence is necessary.

The modalities to treat bleeding polyps include electrocautery snare polypectomy, adrenaline injection, clipping, argon plasma coagulation and surgery. We hereby describe an endoscopic banding ligation method for the management of bleeding gastric polyp in a patient receiving antiplatelet therapy. A 66-year-old man presented with a five month-history of intermittent tarry stool passage, nausea and fatigue. He had a past history of peripheral arterial occlusive disease and non-insulin dependent diabetes mellitus with end stage renal disease, and regularly took antiplatelet agent (ticlopidine 100 mg thrice daily) for cardiovascular prophylaxis. On examination, the patient was grossly pale, ill in appearance, with a pulse of 110/min and blood pressure of 108/76 mmHg. Laboratory examination revealed hemoglobin of 7.8 g/dl. Endoscopic examination revealed a bleeding sessile polyp over the posterior wall of the antrum. Endoscopic banding ligation was carried out by a pneumoactivated esophageal variceal ligation device set. Bleeding stopped immediately following the procedure, and the patient recovered uneventfully. It is suggested that endoscopic banding ligation is a safe and effective technique for the treatment of bleeding gastrointestinal polyps in patients receiving antiplatelet therapy.

Background: Sometimes, no definite filling defect could be found by cholangiogram (ERC) during the endoscopic retrograde cholangio-pancreatiographic (ERCP) exam; even prior images had evidence of common bile duct stones (CBDS). We aimed in estimating the positive rate of extraction of CBDS who had treated by endoscopic sphincterotomy/endoscopic papillary balloon dilation (EST/EPBD) with negative ERC finding., Methods: One hundred forty-one patients with clinically suspicious of CBDS but negative ERC, who had received EST/EPBD treatments was enrolled. Potential factors for predicting CBDS, as well as the treatment-related complications were analyzed., Results: Nearly half of the patients with negative ERC, had a positive stone extraction. Only patients with high probability of CBDS were significantly associated with positive stone extraction. Moreover, patients with intermediate probability of CBDS had higher rates of overall complications, including post-ERCP pancreatitis. In addition, no significant difference of post-ERCP pancreatitis was found between EST and EPBD groups in any one group of patients with the same probability of CBDS., Conclusions: Regarding patients with negative ERC, therapeutic ERCP is beneficial and safe for patients present with high probability of CBDS. Moreover, under the same probability of CBDS, there was no significance difference in post-ERCP pancreatitis between EST and EPBD.

Background: WA-25 (dihydroaustrasulfone alcohol, a synthetic derivative of marine compound WE-2) suppresses atherosclerosis in rats by reducing neointima formation. Because angiogenesis plays a critical role in the pathogenesis of atherosclerosis, the present study investigated the angiogenic function and mechanism of WA-25., Methods: The angiogenic effect of WA-25 was evaluated using a rat aortic ring assay and transgenic zebrafish models were established using transgenic Tg(fli-1:EGFP)y1 and Tg(kdrl:mCherryci5-fli1a:negfpy7) zebrafish embryos. In addition, the effect of WA-25 on distinct angiogenic processes, including matrix metalloproteinase (MMP) expression, endothelial cell proliferation and migration, as well as tube formation, was studied using human umbilical vein endothelial cells (HUVECs). The effect of WA-25 on the endothelial vascular endothelial growth factor (VEGF) signaling pathway was elucidated using qRT-PCR, immunoblot analysis, immunofluorescence and flow cytometric analyses., Results: The application of WA-25 perturbed the development of intersegmental vessels in transgenic zebrafish. Moreover, WA-25 potently suppressed microvessel sprouting in organotypic rat aortic rings. Among cultured endothelial cells, WA-25 significantly and dose-dependently inhibited MMP-2/MMP-9 expression, proliferation, migration and tube formation in HUVECs. Mechanistic studies revealed that WA-25 significantly reduced the VEGF release by reducing VEGF expression at the mRNA and protein levels. In addition, WA-25 reduced surface VEGF receptor 2 (VEGFR2/Flk-1) expression by repressing the VEGFR2 mRNA level. Finally, an exogenous VEGF supply partially rescued the WA-25-induced angiogenesis blockage in vitro and in vivo., Conclusions: WA-25 is a potent angiogenesis inhibitor that acts through the down-regulation of VEGF and VEGFR2 in endothelial cells., General Significance: WA-25 may constitute a novel anti-angiogenic drug that acts by targeting endothelial VEGF/VEGFR2 signaling.

Background. No study investigated the efficacy and safety of endoscopic papillary balloon dilation (EPBD) for the treatment of acute biliary pancreatitis (ABP). Method. We retrospectively reviewed the effects of EPBD on patients with ABP from February 2003 to December 2012. The general data, findings of image studies, details of the procedure, and outcomes after EPBD were analyzed. Result. Total 183 patients (male/female: 110/73) were enrolled. The mean age was 65.9 years. Among them, 155 patients had mild pancreatitis. The meantime from admission to EPBD was 3.3 days. Cholangiogram revealed filling defects inside the common bile duct (CBD) in 149 patients. The mean dilating balloon size was 10.5 mm and mean duration of the dilating procedure was 4.3 minutes. Overall, 124 patients had gross stones retrieved from CBD. Four (2.2%) adverse events and 2 (1.1%) intraprocedure bleeding incidents but no procedure-related mortality were noted. Bilirubin and amylase levels significantly decreased after EPBD. On average, patients resumed oral intake within 1.4 days. The clinical parameters and outcomes were similar in patients with different severity of pancreatitis. Conclusion. EPBD can be effective and safe for the treatment of ABP, even in patients presenting with severe disease.

Background: Endoscopic sphincterotomy (ES) is an established treatment for patients with choledocholithiasis or common bile duct stones (CBDS), but further management of patients after ES with recurrent CBDS remains controversial. Endoscopic papillary large balloon dilation (EPLBD) has been used safely and effectively for stone removal in patients after ES with recurrent CBDS. The aim of this study was to evaluate the clinical efficacy of EPLBD in patients after complete ES with recurrent CBDS., Methods: Records of 891 patients with CBDS after complete ES from January 1991 to December 2008 were reviewed. Of 133 patients with recurrent CBDS, 122 had complete endoscopic bile duct clearance. Twenty-three patients (Group 1) underwent EPLBD and 99 (Group 2) underwent stone extraction without dilatation. Basic demographics and endoscopic findings at the first recurrence were recorded and analyzed. The primary end point was the second CBDS recurrence., Results: No statistical differences were observed between the two groups, except for larger CBDS size in Group 1. The bile duct clearance rate was 96% in Group 1 and 91% in Group 2. No complications such as pancreatitis, perforation, and bleeding were noted in Group 1, and one patient in Group 2 suffered from bleeding after stone extraction. The rate of second recurrent CBDS after endoscopic clearance for the first recurrent CBDS was 17% in Group 1 and 60% in Group 2 (p < 0.001). There were two independent factors for the second recurrence, including cirrhosis (odds ratio 4.734, p = 0.023) and stone extraction directly without major papilla expansion (odds ratio 6.050, p = 0.003)., Conclusion: EPLBD is a safe and effective endoscopic treatment for recurrent CBDS in patients after ES. It can also facilitate complete clearance of CBDS and prevent further CBDS recurrence., (Copyright © 2014. Published by Elsevier Taiwan.)

Background: Gene therapy of proopiomelanocortin, the precursor of α-melanocyte-stimulating hormone (α-MSH), suppresses the neovascularization in tumors. However, the roles of α-MSH in angiogenesis remain unclear., Methods: The influence of α-MSH on angiogenesis was evaluated by ex vivo rat aorta and in vivo, including transgenic zebrafish and chicken chorioallantoic membrane (CAM) assays. The effect of α-MSH on proliferation, matrix metalloproteinase (MMP) secretion, migration and tube formation was examined using human umbilical vein endothelial cells (HUVECs). The expression of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) was investigated by quantitative RT-PCR, immunoblot and immunofluorescent analysis. Antibodies' neutralization was employed to dissect the receptor(s) transmitting α-MSH signaling., Results: Application of α-MSH potently suppressed the microvessels sprouting in organotypic aortic rings. Besides, α-MSH perturbed the vessels development in zebrafish and chicken embryos. α-MSH (0.01-10nM) inhibited the MMP-2 secretion, migration and tube formation of HUVECs without affecting proliferation. Mechanistic studies unveiled α-MSH decreased the VEGF expression and release in HUVECs. Besides, α-MSH downregulated the VEGFR2 expression at transcriptional and translational levels. Importantly, α-MSH attenuated the Akt phosphorylation, but enhanced the expression of PTEN, endogenous antagonist of PI3K/Akt signaling. Expression analysis and antibody neutralization revealed that MC1-R and MC2-R participated in α-MSH-induced blockage of migration and VEGF/VEGFR2/Akt signaling. However, VEGF supply failed to reverse the anti-angiogenic function of α-MSH., Conclusions: α-MSH inhibits the physiological angiogenesis by attenuating VEGF/VEGFR2/Akt signaling in endothelial cells., General Significance: α-MSH is a potent angiogenesis inhibitor targeting at endothelial VEGF/VEGFR2 signaling, which may have potential for therapeutic application., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Celecoxib, a COX-2 inhibitor and non-steroidal anti-inflammatory drug, can prevent several types of cancer, including hepatocellular carcinoma (HCC). Here we show that celecoxib suppressed the self-renewal and drug-pumping functions in HCC cells. Besides, celecoxib depleted CD44+/CD133+ hepatic cancer stem cells (hCSC). Prostaglandin E2 (PGE2) and CD133 overexpression did not reverse the celecoxib-induced depletion of hCSC. Also, celecoxib inhibited progression of rat Novikoff hepatoma. Moreover, a 60-day celecoxib program increased the survival rate of rats with hepatoma. Histological analysis revealed that celecoxib therapy reduced the abundance of CD44+/CD133+ hCSCs in hepatoma tissues. Besides, the hCSCs depletion was associated with elevated apoptosis and blunted proliferation and angiogenesis in hepatoma. Celecoxib therapy activated peroxisome proliferator-activated receptor γ (PPARγ) and up-regulated PTEN, thereby inhibiting Akt and disrupting hCSC expansion. PTEN gene delivery by adenovirus reduced CD44/CD133 expression in vitro and hepatoma formation in vivo. This study suggests that celecoxib suppresses cancer stemness and progression of HCC via activation of PPARγ/PTEN signaling.

Background: Proton pump inhibitor and histamine-2 receptor antagonist can prevent aspirin-related ulcers/erosions but few studies compare the efficacy of these two agents. Aims. We evaluated the efficacy of omeprazole and famotidine in preventing recurrent ulcers/erosions in low-dose aspirin users., Methods: The 24-week clinical outcomes of the patients using low-dose aspirin for cardiovascular protection with a history of ulcers/erosions and cotherapy of omeprazole or famotidine were retrospectively reviewed. The incidence of gastrointestinal symptoms, recurrent ulcers/erosions, erosive esophagitis, gastrointestinal bleeding, and thromboembolic events was analyzed., Results: A total of 104 patients (famotidine group, 49 patients; omeprazole group, 55 patients) were evaluated. Famotidine group had more gastrointestinal symptoms episodes than omeprazole group (46.9% versus 23.6%, P=0.01). Fifteen famotidine group patients and 5 omeprazole group patients had recurrent ulcers/erosions (30.6% versus 9.1%, P=0.005). Lanza scale was significantly lower in omeprazole group than in famotidine group (1.2±0.7 versus 1.7±1.1, P=0.008). Only 1 famotidine group patient had ulcer bleeding. The incidences of erosive esophagitis and thromboembolic events were comparable between both groups., Conclusions: Omeprazole was superior to famotidine with less gastrointestinal symptoms and recurrent ulcers/erosions in patients using 24-week low-dose aspirin. The risk of erosive esophagitis, gastrointestinal bleeding, and thromboembolic events was similar between both groups.

Background: Less than 67% of patients with intermediate risk for common bile duct (CBD) stones require therapeutic intervention. It is important to have an accurate, safe, and reliable method for the definitive diagnosis of CBD stones before initiating therapeutic endoscopic retrograde cholangiopancreatography (ERCP). Few publications detail the diagnostic efficacy of linear echoendoscopy (EUS) for CBD stones., Methods: 30 patients with biliary colic, pancreatitis, unexplained derangement of liver function tests, and/or dilated CBD without an identifiable cause were enrolled in the study. When a CBD stone was disclosed by linear EUS, ERCP with stone extraction was performed. Patients who failed ERCP were referred for surgical intervention. If no stone was found by EUS, ERCP would not be performed and patients were followed-up for possible biliary symptoms for up to three months., Results: The major reason for enrollment was acute pancreatitis. The mean predicted risk for CBD stones was 47% (28-61). Of the 12 patients who were positive for CBD stones by EUS, nine had successful ERCP, one failed ERCP (later treated successfully by surgical intervention) and two were false-positive cases. No procedure-related adverse events were noted. For those 18 patients without evidence of CBD stones by EUS, no false-negative case was noted during the three-month follow-up period. Linear EUS had sensitivity, specificity, positive and negative predicted values for the detection of CBD stones of 1, 0.9, 0.8 and 1, respectively., Conclusion: Linear EUS is safe and efficacious for the diagnosis of occult CBD stones in patients with intermediate risk for the disease.

Background: Endoscopic methods are currently the treatment of choice for patients with common bile duct (CBD) stones, but subsequent management of the intact gallbladder for patients following endoscopic treatment is still controversial. The primary aim of this study was to discover the association between gallbladder status and recurrent biliary complications for patients with CBD stones after endoscopic treatment. Additionally, we also sought to determine risk factors for recurrent biliary complications in these patients., Methods: The records of 1625 patients with CBD stones following endoscopic treatment were reviewed. A total of 681 patients were enrolled and subsequently categorized into four groups: Group 1 (n = 201), calculous gallbladder; Group 2 (n = 140), acalculous gallbladder; Group 3 (n = 175), elective cholecystectomy after endoscopic treatment; and Group 4 (n = 165), prior cholecystectomy. The basic demographics and recurrent biliary complications during follow-up among these four groups were analyzed by Chi-square test, ANOVA, Kaplan-Meier analysis, and log-rank test., Results: During the median follow-up period of 34 months, 133 patients (20%) with recurrent biliary complications were identified. The recurrence rates of Groups 1, 2, 3, and 4 were 29%, 11%, 15%, and 19%, respectively. Kaplan-Meier analysis showed that patients with calculous gallbladder had a significantly higher rate of recurrent biliary complication. In multivariate analysis, patients with a history of cirrhosis, juxta-papillary diverticulum, calculous gallbladder, CBD size ≥ 1.5 cm, and endoscopic management with endoscopic sphincterotomy were at a higher risk for developing biliary complications (p = 0.029, p = 0.039, p < 0.001, p = 0.002, p = 0.021, respectively.), Conclusion: Patients with cholecystolithiasis and CBD stones had a higher incidence of recurrent biliary complications. For some of these patients, elective cholecystectomy following endoscopic treatment may be considered. However, routine elective cholecystectomy in patients with normal gallbladder is not appropriate because of the low recurrence of biliary complications. Whether gallbladder function affects the biliary clearance and biliary complications requires further research., (Copyright © 2012. Published by Elsevier B.V.)

Hepatoma-derived growth factor (HDGF) stimulates the migration, invasion and metastasis in several types of cancer cells. However, the mechanism underlying HDGF-stimulated migration remains unclear. In this study, we investigated the influence of HDGF on cytoskeleton remodeling and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway in non-transformed NIH/3T3 cells. Exogenous HDGF promoted the migration and the formation of dorsal ruffles and podosome rosettes. Besides, HDGF supply increased the PI3K expression and Akt phosphorylation in dose- and time-dependent manners. Application of LY294002, a PI3K inhibitor, attenuated the HDGF-induced migration, dorsal ruffles and podosome rosettes formation. Consistently, the HDGF-overexpressing NIH/3T3 transfectants exhibited significantly increased motility and elevated PI3K/Akt activities, which were repressed by LY294002 or adenovirus-mediated overexpression of endogenous PI3K antagonist, PTEN. In summary, HDGF elicits the activation of PI3K/Akt signaling cascade, thereby promoting cytoskeleton remodeling to stimulate cellular migration., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To evaluate the liver stiffness measurement (LSM) using transient elastography (TE) to predict the risk of esophageal varices (EVs) in Chinese patients., Methods: In total, 46 patients with suspicious or proven liver cirrhosis underwent TE and liver biopsy. All participants were endoscopically screened for the presence of EVs and large EVs by two endoscopists who were blinded to the LSM status. Large EVs were defined as more than 5 mm in diameter. Receiver operating characteristic (ROC) curves for both TE and the platelet count/spleen diameter (PC/SD) ratio in predicting the presence of EVs or large EVs were calculated., Results: Of the 46 patients, 30 (65%) had EVs including 19 (41%) with large EVs. The area under the ROC curve (AUROC) of LSM was 0.85 for the presence of EVs and 0.83 for large EVs, respectively. The cut-off values of LSM were ≥13.4 kPa for the presence of EVs and ≥14.6 kPa for large EVs. Notably, the AUROC of the PC/SD ratio was 0.92 for the presence of EVs but only 0.69 for large EVs., Conclusion: LSM using TE can predict the presence of EVs or large EVs in Chinese patients with suspicious or proven cirrhosis and may identify patients who require endoscopic surveillance., (© 2012 The Authors. Journal of Digestive Diseases © 2012 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.)

Background and Aim: To evaluate the prevalence and risk factors of gastroesophageal reflux disease (GERD) in a general population in Taiwan., Methods: A validated symptom questionnaire, the Chinese GERD questionnaire, was utilized to determine the prevalence of GERD within a community in Taiwan. A cut-off value for GERD diagnosis was a total score ≥ 12. Additionally, demographic data, including sex, age, body mass index, and consumption of tobacco and alcohol, were recorded, and a logistic regression analysis was conducted to search the independent risk factors for the development of GERD in a general population., Results: In total, 1238 residents were recruited for this study. The monthly frequencies of heartburn, epigastric acidic discomfort, and acid regurgitation were 4.4%, 3.7%, and 2.9%, respectively. The GERD prevalence was 25% in the community. The multivariate analysis showed that female sex and age of 40-49 years and 50-59 years were independent risk factors related to the development of GERD, with odd ratios of 1.71, 3.65, and 2.41, respectively (95% confidence intervals: 1.26-2.34, 1.62-8.21, and 1.11-2.54, respectively)., Conclusions: GERD has become a common disorder in the general population in Taiwan. Female sex and age of 40-49 years and 50-59 years are risk factors for the development of GERD within a community., (© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Background: Lethal pancreatitis has been reported after treatment for common bile duct stones using small endoscopic papillary balloon dilation., Methods: We retrospectively evaluated the safety and efficacy of using large balloon dilation alone without the use of sphincterotomy for the treatment of large common bile duct stones in Kaohsiung Veterans General Hospital. Success rate of stone clearance, procedure-related adverse events and incidents, frequency of mechanical lithotripsy use, and recurrent stones were recorded., Results: A total of 247 patients were reviewed in the current study. The mean age of the patients was 71.2 years. Most of them had comorbidities. Mean stone size was 16.4 mm. Among the patients, 132 (53.4%) had an intact gallbladder and 121 (49%) had a juxtapapillary diverticulum. The mean size of dilating balloon used was 13.2 mm. The mean duration of the dilating procedure was 4.7 min. There were 39 (15.8%) patients required the help of mechanical lithotripsy while retrieving the stones. The final success rate of complete retrieval of stones was 92.7%. The rate of pancreatic duct enhancement was 26.7% (66/247). There were 3 (1.2%) adverse events and 6 (2.4%) intra-procedure bleeding incidents. All patients recovered completely after conservative and endoscopic treatment respectively, and no procedure-related mortality was noted. 172 patients had a follow-up duration of more than 6 months and among these, 25 patients had recurrent common bile duct stones. It was significantly correlated to the common bile duct size (p = 0.036), Conclusions: Endoscopic papillary large balloon dilation alone is simple, safe, and effective in dealing with large common bile duct stones in relatively aged and debilitated patients.

Background: The fact that prognoses remain poor in patients with advanced hepatocellular carcinoma highlights the demand for suitable animal models to facilitate the development of anti-cancer medications. This study employed a relatively non-invasive approach to establish an orthotopic hepatocellular carcinoma model in immune-competent rats. This was done by ultrasound-guided implantation of cancer cells and the model was used to evaluate the therapeutic efficacy of short-term and low-dose epirubicin chemotherapy., Methods: Rat Novikoff hepatoma cells were injected percutaneously into the liver lobes of Sprague-Dawley rats under the guidance of high resolution ultrasound. The implantation rate and the correlation between dissected and ultrasound-measured tumor sizes were evaluated. A similar induction procedure was performed by means of laparotomy in a different group of rats. Pairs of tumor measurement were compared by ultrasound and computerized tomography scan. Rats with a successful establishment of the tumor were divided into the treatment (7-day low-dose epirubicin) group and the control group. The tumor sizes were non-invasively monitored by the same ultrasound machine. Blood and tumor tissues from tumor-bearing rats were examined by biochemical and histological analysis respectively., Results: Ultrasound-guided implantation of Novikoff hepatoma cells led to the formation of orthotopic hepatocellular carcinoma in 60.4% (55/91) of the Sprague-Dawley rats. Moreover, tumor sizes measured by ultrasound significantly correlated with those measured by calipers after sacrificing the animals (P < 0.00001). The rate of tumor induction by ultrasound-guided implantation was comparable to that of laparotomy (55/91, 60.4% vs. 39/52, 75%) and no significant difference in sizes of tumor was noted between the two groups. There was a significant correlation in tumor size measurement by ultrasound and computerized tomography scan. In tumor-bearing rats, short-term and low-dose epirubicin chemotherapy caused a significant reduction in tumor growth, and was found to be associated with enhanced apoptosis and attenuated proliferation as well as a decrease in the microvessel density in tumors., Conclusions: Ultrasound-guided implantation of Novikoff hepatoma cells is an effective means of establishing orthotopic hepatocellular carcinoma in Sprague-Dawley rats. Short-term and low-dose epirubicin chemotherapy had perturbed tumor progression by inducing apoptosis and neovascularization blockade.

Goals and Background: Endoscopic treatment is recommended for initial hemostasis in nonvariceal upper gastrointestinal bleeding. Many endoscopic devices have been demonstrated to be effective in the hemostasis of bleeding ulcers. However, the hemostatic efficacy of argon plasma coagulation (APC) has not been widely investigated., Study: From February 2007 to February 2008, 271 consecutive patients with high-risk bleeding ulcers, characterized by active bleeding, nonbleeding visible vessels and adherent clots, were admitted to our hospital. Among these patients, 135 nonrandomly underwent either APC therapy or distilled water injection. Pantoprazole infusion was conducted during the fasting period after endoscopy and orally for 8 weeks to encourage ulcer healing. Episodes of rebleeding were retreated with endoscopic combination therapy. Patients who did not benefit from retreatment underwent emergency surgery., Results: In all,135 patients were enrolled, among whom 6 with gastric malignancy, acute severe illness or multiple bleeding sites were excluded. Finally, hemostatic efficacy in 59 patients treated with APC was prospectively compared with 70 patients treated with distilled water injection. The two treatment groups were similar with respect to all baseline characteristics. Initial hemostasis was accomplished in 57 patients treated with APC, and 64 patients with distilled water injection therapy (97% vs. 91%, P=0.29). Bleeding recurred in 6 patients treated with APC, and in 17 patients treated with distilled water injection (11% vs. 27%, P=0.03). No significant differences were observed between the 2 groups in hospital stay, transfusion requirements, surgery and mortality., Conclusions: Endoscopic therapy with APC is more effective than distilled water injection for preventing rebleeding in the treatment of high-risk bleeding ulcers.

Background: The recurrence rate of common bile duct stones (CBDS) is around 3-21% after treatment by endoscopic sphincterotomy (ES). Fatty meal has been shown to improve hepatic clearance in both patients with intact gallbladder and post-cholecystectomy after ES. This study tested the effects of different kinds of food on hepatic clearance by using quantitative cholescintigraphy (QC) in patients after ES., Methods: Forty-seven patients after ES with abnormal QC were enrolled in our study. Complete ablation of sphincter function was confirmed by sphincter of Oddi manometry. Fasting QC was done in every patient shortly after normalization of liver function, and then followed with low-fat and fatty-meal QC. Each of the 47 subjects was observed for the effect on hepatic clearance at 3 different levels of treatments (diets and fasting). Additionally, possible factors responsible for recurrent CBDS were investigated by means of logistic regression., Results: Both fatty and low-fat meals could significantly improve hepatic clearance compared with fasting in most patients after ES. But the response to food types was individualized. All patients tolerated the meals well. There was no significant relationship between the recurrence of CBDS and sex, age, intact gallbladder and presence of juxtapapillary diverticulum, CBD size, and improvement in hepatic clearance (> or = 5%) by food., Conclusion: Both fatty and low-fat meals improved hepatic clearance in most of the patients with CBDS after ES, but the response to meals was individualized. Therefore, there is no need to restrict the amount of fat intake for patients who have undergone ES.

Background: The unique clinical role of endoscopic retrograde cholangiopancreatography (ERCP) in diagnosing and treating biliary tree diseases cannot be completely replaced by other modern imaging modalities such as magnetic resonance cholangiopancreatography. However, post-ERCP pancreatitis is one of the most common and life-threatening complications. Prophylactic medication in the prevention of pancreatitis during ERCP is still controversial. The objective of the present study was to investigate the role of different regimens of somatostatin in the prevention of acute pancreatitis after ERCP and analyze the risk factors contributing to post-ERCP complications., Methods: From July 1999 to September 2000, 133 patients with benign biliary disease who received ERCP for diagnosis or treatment were enrolled. Group A patients received a bolus of somatostatin infusion before ERCP, followed by continuous infusion for 12 hours. Group B patients received a bolus of somatostatin before ERCP only, and group C patients were the controls who did not receive somatostatin treatment. Serum amylase levels before and 24 hours after ERCP, and abdominal pain were recorded., Results: There were no significant differences in bile duct and pancreatic duct visualization, ratio of diagnostic and therapeutic ERCP, procedure time, post-procedural hyperamylasemia and pancreatitis among the 3 groups. For patients with visualization of the pancreatic duct, the incidences of hyperamylasemia (serum amylase > or = 220 U/L) were higher than in patients without visualization of the pancreatic duct (p < 0.001). All 6 patients with post-ERCP pancreatitis had pancreatic duct visualization, and recovered after conservative treatment., Conclusion: Continuous infusion of somatostatin after ERCP does not seem to be helpful in the prevention of pancreatic complications after ERCP. Pancreatic duct visualization is a risk factor for pancreatic complications.

Background: Tumorigenesis is a multistep process that begins with the abrogation of normal controls of apoptosis and cell proliferation, and the FAS receptor-ligand system is a key regulator of apoptosis. The aim of this study was to investigate whether functional polymorphisms of death pathway genes (FAS and FASL) are associated with the development of gastric atrophy and intestinal metaplasia., Patients and Methods: Genotypes in the promoter regions of the FAS (-1377G/A and -670A/G) and FASL (-844T/C) genes of 101 healthy individuals and 86 gastric cancer patients were determined by PCR-RFLP. Additionally, gastric histological changes were examined according to the updated Sydney System., Results: The carriage of FASL -844C allele significantly increased the risk of atrophy in the gastric corpus, with an adjusted odds ratio (OR) of 5.0 [95% confidence interval (CI), 1.5-6.8]. There were no gene-gene interactions among FASL -844T/C, FAS -1377G/A and FAS -670A/G polymorphisms in developing premalignant gastric lesions. In the 109 individuals with Helicobacterpylori infection, carrying the FAS -1377A allele was a protective factor for developing intestinal metaplasia in the antrum (OR, 0.3; 95% CI, 0.1-0.9), while carrying the FASL -844C allele was a risk factor for developing gastric atrophy in the corpus (OR, 9.4; 95% CI, 1.7-53.4)., Conclusion: FAS and FASL genotypes of the hosts are important determinants in the pathogenesis of gastric atrophy and intestinal metaplasia in H. pylori-infected individuals.

Aim: To report the clinical experiences in the application of clip-assisted endoscopic method for nasoenteric feeding in patients with gastroparesis and patients with gastroesophageal wounds, and to compare the efficacy of nasoenteric feeding in these two indications., Methods: From April 2002 to January 2004, 21 consecutive patients with gastroparesis or gastroesophageal wounds were enrolled and received nasoenteric feeding for nutritional support. A clip-assisted method was used to place the nasoenteric tubes. Outcomes in the two groups were compared with respect to the successful rate of enteral feeding, percentage of recommended energy intake (REI), and complication rates., Results: The gastroparesis group included 13 patients with major burns (n = 7), trauma (n = 2), congestive heart failure (n = 2) and post-surgery gastric stasis syndrome (n = 2). The esophageogastric wound group included eight patients with tracheoesophageal fistula (n = 2) and wound leakage following gastric surgery (n = 6). Two study groups were similar in feeding successful rates (84.6% vs 75.0%). There were also no differences in the percentage of REI between groups (79.4% vs 78.6%). Additionally, no complications occurred in any of the study groups., Conclusion: Nasoenteric feeding is a useful method to provide nutritional support to most of the patients with gastroparesis who cannot tolerate nasogastric tube feeding and to the cases who need bypass feeding for esophageogastric wounds.

Background and Aim: The role of juxtapapillary diverticulum ( JPD) in biliary stone formation is controversial. This study was designed to understand the relationship between the size of JPD, hepatic clearance and recurrent bile duct stones in patients after endoscopic sphincterotomy., Methods: Five hundred and twenty patients with choledocholithiasis who had received endoscopic sphincterotomy were enrolled. They were divided into three groups: group A (n = 268) without diverticula; group B (n = 156) with small diverticula; and group C (n = 96) with large diverticula. All patients were regularly followed with interviews, liver function test and sonogram to detect the recurrent bile duct stones. Quantitative cholescintigraphy was performed in 176 cholecystectomized patients to evaluate the hepatic clearance. Sphincter of Oddi manometry was performed to exclude incomplete sphincterotomy if quantitative cholescintigraphy was abnormal., Results: After 9-111 months of follow-up, 76 patients had recurrent bile duct stones. There was a significant higher bile duct stone recurrence in group C than in group A (P < 0.01), but no statistical difference was noted between group B and group A (P = 0.2). Patients with JPD were older than those without (P < 0.05). Of 176 cholecystectomized patients, two were excluded because sphincter of Oddi basal pressure was more than 10 mmHg. In the remaining 174 patients, the E45' was significantly lower in group C than in group A (41.2% +/- 18.6%vs 49.1% +/- 14.1%; P < 0.05), and there was no significant difference between group B and group A., Conclusions: JPD is a predisposing factor of delayed biliary emptying and it increases the chance and incidence of recurrent bile duct stones.

Aim: Bleeding and perforation are the major and serious complications associated with endoscopic polypectomy. To develop a safe and effective method to resect hyperplastic polyps of the stomach, we employed rubber bands to strangulate hyperplastic polyps and to determine the possibility of inducing avascular necrosis in these lesions., Methods: Forty-seven patients with 72 hyperplastic polyps were treated with endoscopic banding ligation (EBL). On 14 days after endoscopic ligation, follow-up endoscopies were performed to assess the outcomes of the strangulated polyps., Results: After being strangulated by the rubber bands, all of the polyps immediately became congested (100%), and then developed cyanotic changes (100%) approximately 4 minutes later. On follow-up endoscopy 2 weeks later, all the polyps except one had dropped off. The only one residual polyp shrank with a rubber band in its base, and it also dropped off spontaneously during subsequent follow-up. No complications occurred during or following the ligation procedures., Conclusion: Gastric polyps develop avascular necrosis following ligation by rubber bands. Employing suction equipment, EBL can easily capture sessile polyps. It is an easy, safe and effective method to eradicate hyperplastic polyps of the stomach.

Gastroenterologists are often frustrated in their efforts to deliver a feeding tube by endoscopic guidance into the small bowel because of retrograde migration during the withdrawal of the endoscope. We describe a clip assisted endoscopic method whereby a nasoenteric feeding tube can be reliably delivered into the distal duodenum. A nasoduodenal tube with a 3-0 silk suture sewn on its distal tip is inserted into the stomach. The suture on the feeding tube is grasped by a clip-fixing device. Then, the endoscope with feeding tube is advanced into the distal duodenum and the tube is fixed on a mucosal fold by clipping. We used this technique to successfully place nasoenteric tubes into the distal duodenum in 9 patients. There were no procedure-related complications, and no bleeding or perforation due to removal of the feeding tubes was observed. We conclude that this clip-assisted endoscopic method is a reliable modality for placing nasoenteric tubes.

Background: Although endoscopic hemoclip therapy is widely used in the treatment of GI bleeding, there are few prospective trials that assess its efficacy. This study evaluated the efficacy and safety of hemoclip placement and distilled water injection for the treatment of high-risk bleeding ulcers., Methods: Seventy-nine patients with major stigmata of ulcer hemorrhage were randomly assigned to either endoscopic hemoclip placement (n = 39) or injection with distilled water (n = 40)., Results: Initial hemostasis was achieved in all patients treated with hemoclips and 39 treated by distilled water injection (respectively, 100.0% vs. 97.5%; p = 1.00). Bleeding recurred in 4 and 11 of patients, respectively, in the hemoclip and water injection groups. It occurred significantly more frequently in the injection group (hemoclip, 10.3%; injection, 28.2%; p = 0.04). No major procedure-related complication occurred in either group. Emergency operations were performed in 5.1% of patients treated with hemoclips versus 12.5% of those in the water injection group (p = 0.43). Hospital days and mortality rate were similar in both groups., Conclusion: Endoscopic hemoclip placement is a safe and effective hemostatic method that is superior to distilled water injection for treatment of bleeding peptic ulcer.

Background: As many as 24% of patients who undergo endoscopic sphincterotomy for the removal of bile duct stones have recurrent biliary complications develop for which there is no effective method of prevention. The aim of this study was to determine whether patients who undergo routine clinical follow-up after endoscopic sphincterotomy for bile duct stones have a different outcome than those who do not., Methods: All patients who had endoscopic sphincterotomy for bile duct stones were scheduled for follow-up visits, liver function tests, and transabdominal US every 3 to 6 months. ERCP was performed whenever symptoms recurred, or abnormal liver function or US was noted. The patients themselves decided whether to adhere to the follow-up schedule; this was not a randomized trial., Results: Seven hundred sixty-seven patients underwent endoscopic sphincterotomy for bile duct stones from October 1990 to July 1999. Seventy-seven (10%) were found to have recurrent bile duct stones. Three patients who had undergone Billroth II gastrectomy were excluded. Among the remaining 74 patients (52 men, 22 women; mean age 65 years), 42 (57%) had a juxtapapillary diverticulum and 21 (28%) an intact gallbladder. The mean time to recurrence of bile duct stones was 19.7 months (range 5-72 months). Sixty-four patients (87%) had recurrent bile duct stones within 3 years. Fifty-one (69%) were followed regularly (Group A) and 23 (31%) were not (Group B). At the time of stone recurrence, 20 patients in Group A (39%) and 1 in Group B (4%) were asymptomatic (p = 0.002). Liver function tests were normal in 17 patients (13 Group A, 4 Group B). Endoscopic treatment for recurrent bile duct stones was successful in 46 patients (90%) in Group A and 16 (70%) in Group B (p = 0.04); surgical treatment was successful in all 5 patients in Group A and 4 of the 7 patients in Group B. Two patients in Group B were treated by nasobiliary drainage and biliary endoprosthesis insertion caused by extremely large stones and poor condition; both died (acute pancreatitis and sepsis)., Conclusion: Regular follow-up after endoscopic sphincterotomy detects recurrent bile duct stones early and thus avoids complications of bile duct stones.

Background: Hepatic clonorchiasis is endemic in areas of the Far East, including Taiwan, where people commonly eat raw or partially cooked freshwater fish., Goals: To analyze and explore the cholangiographic findings of hepatic clonorchiasis with respect to the clinical data., Study: From February 1990 to May 1999, 64 patients were diagnosed with hepatic clonorchiasis in the Kaoshiung Veterans General Hospital. Eighteen of the 64 patients were indicated for endoscopic retrograde cholangiopancreatography (ERCP). The final diagnosis was confirmed by identification of ova in bile or worms in the biliary tract., Results: Fifteen (83%) of 18 patients had history of raw fish consumption and seven patients (39%) came from an endemic area. Clinically, cholangitis (8 of 18) was the most frequent indication for ERCP. All of the patients were diagnosed by the presence of ova in bile. Only seven (39%) patients had peripheral eosinophilia, and seven (39%) had ova in stool. The most characteristic cholangiographic finding of hepatic clonorchiasis in ERCP is filamentous or elliptic filling defects of the biliary tract (16 of 18)., Conclusion: When presented with biliary symptoms, a history of raw fish consumption in an endemic area should arouse suspicion of hepatic clonorchiasis. Filamentous filling defects in ERCP with bile analysis may confirm the diagnosis.