Microalgal extract from thermotolerant Coelastrella sp. F50 retards the liver tumor progression by targeting hepatic cancer stem cells.

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 (PGE2 ) axis in HCC cells and rat hepatoma, and exogenous PGE2 restored CSCs properties in F50-treated HCC cells. In summary, F50 extract inhibits hepatic CSCs by COX-2/PGE2 downregulation and may facilitate a novel phytotherapy for HCC prevention.

Hepatoma-derived growth factor participates in concanavalin A-induced hepatitis.

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-1ß (IL-1ß)/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-1ß/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.

Celecoxib enhances the therapeutic efficacy of epirubicin for Novikoff hepatoma in rats.

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.

Does preserved sphincter of Oddi function prevent common bile duct stones recurrence in patients after endoscopic papillary balloon dilation?

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.

Successful hemostasis and resection of a bleeding gastric polyp by endoscopic banding ligation in a uremic patient taking antiplatelet agent.

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.

Coral-derived compound WA-25 inhibits angiogenesis by attenuating the VEGF/VEGFR2 signaling pathway.

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.

Celecoxib suppresses hepatoma stemness and progression by up-regulating PTEN.

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.

α-Melanocyte-stimulating hormone inhibits angiogenesis through attenuation of VEGF/VEGFR2 signaling pathway.

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.

The relationship between gallbladder status and recurrent biliary complications in patients with choledocholithiasis following endoscopic treatment.

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.

Hepatoma-derived growth factor stimulates podosome rosettes formation in NIH/3T3 cells through the activation of phosphatidylinositol 3-kinase/Akt pathway.

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.

Efficacy of transient elastography in screening for large esophageal varices in patients with suspicious or proven liver cirrhosis.

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.

Endoscopic papillary large balloon dilation alone without sphincterotomy for the treatment of large common bile duct stones.

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.

Prevalence of gastroesophageal reflux disease in a general population in Taiwan.

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.

Rapid induction of orthotopic hepatocellular carcinoma in immune-competent rats by non-invasive ultrasound-guided cells implantation.

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.

Comparison of hemostatic efficacy for argon plasma coagulation and distilled water injection in treating high-risk bleeding ulcers.

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.

Polymorphisms of death pathway genes FAS and FASL and risk of premalignant gastric lesions.

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.

Clinical application of clip-assisted endoscopic method for nasoenteric feeding in patients with gastroparesis and gastroesophageal wounds.

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.

Endoscopic banding ligation can effectively resect hyperplastic polyps of stomach.

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.

Clip-assisted endoscopic method for placement of a nasoenteric feeding tube into the distal duodenum.

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.