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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: 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 &y& Elsevier]

Abstract: 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 &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

To evaluate the prevalence and risk factors of gastroesophageal reflux disease (GERD) in a general population in Taiwan. 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. 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). 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. [ABSTRACT FROM AUTHOR]

Background: To determine the change of oesophageal manometry in patients with oesophageal varices before and after oesophageal variceal ligation (EVL). Methods: Forty-five patients who had liver cirrhosis and oesophageal varices with high risk of bleeding were managed by EVL. Oesophageal manometry was performed just prior to the ligation and 4–6 weeks after obliteration of varices. Another 45 age- and sex-matched patients without hepatic, oesophageal or systemic disease served as the control group. Results: At 5 cm above the lower oesophageal sphincter (LES), the amplitude of the contractive wave was significantly lower in patients before EVL (56.9 ± 31.8 vs 80.1 ± 30.1, P < 0.05) and returned to the level of control subjects after EVL (76.5 ± 37.0 vs 80.1 ± 30.1, P > 0.05). At 10 cm above LES, the amplitude of the contractive wave was significantly lower in patients before and after EVL than the control group (54.3 ± 29.2 vs 68.1 ± 29.5, 54.2 ± 26.0 vs 68.1 ± 29.5, respectively, P < 0.05). The percentage of tertiary waves was significantly higher in patients before and after EVL than in the control group (31.4 ± 36.6 vs 5.8 ± 15.1, 26.9 ± 32.9 vs 5.8 ± 15.1, respectively, P < 0.05). However, no significant swallowing disturbance was noted in patients after EVL. There was significantly greater LES length in patients before EVL (4.0 ± 0.9 vs 3.4 ± 0.7, P < 0.05) but there was no significant difference in the LES length after EVL as compared with the control group. Eighty-six per cent (39/45) of patients developed para-oesophageal varices and 31% (14/45) developed new varices 6 months after variceal obliteration. However, there was no significant difference in manometry at the time of variceal obliteration between patients with variceal recurrence and those without. Conclusions: The presence of varices affected oesophageal motility. However, such abnormality had little clinical significance. Endoscopic variceal ligation normalized oesophageal motility and may not induce abnormal oesophageal motility. The manometric change can not be used to predict the recurrence of varices in cirrhotic patients after variceal obliteration. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]