Progression of gastric variceal hemorrhage (GVH) is poorer than esophageal variceal bleeding. However, data on its optimal treatment are limited. We designed a prospective study to compare the efficacy of endoscopic band ligation (GVL) and endoscopic N-butyl-2-cyanoacrylate injection (GVO). Liver patients with cirrhosis with or without concomitant hepatocellular carcinoma (HCC) and patients presenting with acute GVH were randomized into two treatment groups. Forty-eight patients received GVL, and another 49 patients received GVO. Both treatments were equally successful in controlling active bleeding (14/15 vs. 14/15, P ‫؍‬ 1.000). More of the patients who underwent GVL had GV rebleeding (GVL vs. GVO, 21/48 vs. 11/49; P ‫؍‬ .044). The 2-year and 3-year cumulative rate of GV rebleeding were 63.1% and 72.3% for GVL, and 26.8% for both periods with GVO; P ‫؍‬ .0143, log-rank test. The rebleeding risk of GVL was sustained throughout the entire follow-up period. Multivariate Cox regression indicated that concomitance with HCC (relative hazard: 2.453, 95% CI: 1.036-5.806, P ‫؍‬ .041) and the treatment method (GVL vs. GVO, relative hazard: 2.660, 95% CI: 1.167-6.061, P ‫؍‬ .020) were independent factors predictive of GV rebleeding. There was no difference in survival between the two groups. Severe complications attributable to these two treatments were rare. In conclusion, the efficacy of GVL to control active GVH appears not different to GVO, but GVO is associated with a lower GV rebleeding rate. (HEPATOLOGY 2006;43:690-697.) A lthough the outcome of variceal hemorrhage has improved over the past two decades, variceal hemorrhage is still the most serious complication of portal hypertension and chronic liver disease. 1 Although bleeding occurs less often from gastric varices (GV) than from esophageal varices (EV) (esophageal variceal hemorrhage [EVH] accounts for 70% to 80% of variceal hemorrhage), it has a poorer prognosis and is associated with more severe blood loss, a higher rebleeding rate, and a higher mortality rate. 1-3 However, limited data exist on the best treatment for GV hemorrhage (GVH). Endoscopic treatment is an alternative in the management of GVH and includes endoscopic injection of sclerosants or thrombin, 4,5 endoscopic band ligation, 6,7 and others. The success rate in controlling GVH by endoscopic injection of N-butyl-2-cyanoacrylate (GVO) appears higher than for other sclerosants according to previous non-randomized trials. 8,9 Though endoscopic variceal ligation is regarded as the optimal endoscopic treatment for EVH, 10 its safety and efficacy for the treatment of GVH is uncertain. 7,11 The rebleeding rate of GVO is variable and ranges from 10% to 42%. 12 At the time we started this trial, there were no randomized control trials, and even now, there is only one relatively small randomized clinical trial, 13 which was conducted to compare these two potential treatment modalities (endoscopic band ligation [GVL] vs. GVO) on the GVH; it showed results in favor of GVO for the treatment of GVH. We...

Bacterial infection may adversely affect the hemostasis of patients with gastroesophageal variceal bleeding (GEVB). Antibiotic prophylaxis can prevent bacterial infection in such patients, but its role in preventing rebleeding is unclear. Over a 25-month period, patients with acute GEVB but without evidence of bacterial infection were randomized to receive prophylactic antibiotics (ofloxacin 200 mg i.v. q12h for 2 days followed by oral ofloxacin 200 mg q12h for 5 days) or receive antibiotics only when infection became evident (on-demand group). Endoscopic therapy for the GEVB was performed immediately after infection work-up and randomization. Fifty-nine patients in the prophylactic group and 61 patients in the on-demand group were analyzed. Clinical and endoscopic characteristics of the gastroesophageal varices, time to endoscopic treatment, and period of follow-up were not different between the two groups. Antibiotic prophylaxis decreased infections (2/59 vs. 16/61; P < .002). The actuarial probability of rebleeding was higher in patients without prophylactic antibiotics (P ‫؍‬ .0029). The difference of rebleeding was mostly due to early rebleeding within 7 days (4/12 vs. 21/27, P ‫؍‬ .0221). The relative hazard of rebleeding within 7 days was 5.078 (95% CI: 1.854 -13.908, P < .0001). The multivariate Cox regression indicated bacterial infection (relative hazard: 3.85, 95% CI: 1.85-13.90) and association with hepatocellular carcinoma (relative hazard: 2.46, 95% CI: 1.30 -4.63) as independent factors predictive of rebleeding. Blood transfusion for rebleeding was also reduced in the prophylactic group (1.40 ؎ 0.89 vs. 2.81 ؎ 2.29 units, P < .05). There was no difference in survival between the two groups. In conclusion, antibiotic prophylaxis can prevent infection and rebleeding as well as decrease the amount of blood transfused for patients with acute GEVB following endoscopic treatment. (HEPATOLOGY 2004;39:746 -753.)

Hepatitis C virus (HCV) causes a persistent infection, chronic hepatitis and hepatocellular carcinoma. HCV NS5A, one of non-structural proteins of HCV, was suggested to play a role in oncogenic transformation. Since the tumor suppressor p53 is important for preventing neoplastic transformation, we investigated the functional effects of HCV NS5A on p53. In vitro and in vivo coimmunoprecipitation and confocal microscopy were used to determine the interaction of NS5A and p53. HCV NS5A binds directly to p53 and colocalizes p53 in the perinuclear region. NS5A inhibits transcriptional transactivation by p53 in a dose-dependent manner by use of a reporter assay. Down regulation of endogenous p21/waf1 expression, which is activated by p53 in Hep3B cells, by NS5A was demonstrated by using FLAG-and FLAG-NS5A Hep3B stable cell lines. The effect of NS5A on p53-mediated apoptosis was determined by flow cytometry in both NS5A permanently and transiently transfected Hep3B cells with exogenous p53. The p53-induced apoptosis was abrogated by NS5A and the inhibition effect correlates well with the binding ability of NS5A to p53. In addition, HCV NS5A protein interacts with and colocalizes hTAF II 32, a component of TFIID and an essential coactivator of p53, in vivo. These results suggest that HCV NS5A interacts with and partially sequestrates p53 and hTAF II 32 in the cytoplasm and suppresses p53-mediated transcriptional transactivation and apoptosis during HCV infection, which may contribute to the hepatocarcinogenesis of HCV infection.

Background-Reactive oxygen species and related oxidative damage have been implicated in the initiation of acute pancreatitis. Changes in these parameters during disease progression merit further investigation. Aims-To evaluate changes and the clinical relevance of superoxide radicals, endogenous antioxidants, and lipid peroxidation during the course of acute pancreatitis. Patients and methods-Superoxide radicals (measured as lucigenin amplified chemiluminescence), ascorbic acid, dehydroascorbic acid, tocopherol, and lipid peroxidation (measured as thiobarbiturate reactive substances) were analysed in blood samples from 56 healthy subjects, 30 patients with mild acute pancreatitis, and 23 patients with severe acute pancreatitis. The association with grades of disease severity was analysed. Measurements were repeated one and two weeks after onset of pancreatitis. Results-In the blood from patients with acute pancreatitis, there were increased levels of the superoxide radical as well as lipid peroxides. There was notable depletion of ascorbic acid and an increased fraction of dehydroascorbic acid. Changes in tocopherol were not great except in one case with poor prognosis. DiVerences between severe and mild acute pancreatitis were significant (p<0.01). Variable but significant correlations with disease severity scores were found for most of these markers. The normalisation of these indexes postdated clinical recovery one or two weeks after onset of disease. Conclusions-Heightened oxidative stress appears early in the course of acute pancreatitis and lasts longer than the clinical manifestations. The dependence of disease severity on the imbalance between oxidants and natural defences suggests that oxidative stress may have a pivotal role in the progression of pancreatitis and may provide a target for treatment. (Gut 1998;42:850-855)

Preoperative serum VEGF is a significant independent predictor of tumor recurrence, DFS, and OS in patients with resectable HCC.

In vitro studies have shown that estrogen and progesterone can affect the contractile response and myoelectric activity of the gastrointestinal smooth muscle. The present study was designed to investigate the effect of sex steroid hormones on gastric emptying and gastrointestinal transit were assessed in rats 15 min after intragastric instillation of a test meal containing charcoal and 51Cr. Gastric emptying was determined by measuring the amount of labeled chromium contained in the small intestine as a percentage of the initial amount received. Gastrointestinal transit was evaluated by calculating both the geometric center of distribution of the radiolabeled marker and the charcoal transit in the intestine. The experimental animals included diestrus rats; ovariectomized rats treated with vehicle, estradiol, and/or progesterone; and normal male and orchiectomized rats treated with vehicle or testosterone. Female rats in diestrus had a slower gastric emptying and a lesser geometric center value than ovariectomized rats. Estradiol inhibited gastric emptying but did not affect gastrointestinal transit. Progesterone increased gastric emptying. Progesterone at lower dose (10 mg/kg) decreased the geometric center compared with higher doses (20 or 40 mg/kg) or vehicle controls. A mixture of estradiol (10 micrograms/kg) and progesterone (20 mg/kg) inhibited gastric emptying to a similar degree as estradiol (10 micrograms/kg) did. Testosterone had no influence on gastric emptying or gastrointestinal transit. These results suggest that estradiol and a mixture of estradiol and progesterone inhibit, whereas progesterone enhances, gastric emptying. Testosterone did not play a role in gastrointestinal motility.

No abstract

Irritable bowel syndrome (IBS) has been one of the commonly presented gastrointestinal disorders. It is of interest how commonly it presents in the society. Western studies indicated that most population-based IBS prevalences range 10%-15%. It is believed that IBS is prevalent in both East and West countries without a significant prevalence difference. Most recently, the Asia IBS prevalence has a higher trend in the affluent cities compared to South Asia. Since many Asia IBS prevalence studies have been published in the recent decade, we could compare the IBS prevalence data divided by various criteria in looking whether they were also comparable to this of West community. Summarized together, most Asia community IBS prevalences based on various criteria are usually within the range 1%-10% and are apparently lower than these of selected populations. Within the same population, the prevalence orders are first higher based on Manning criteria, then followed by Rome I criteria and finally reported in Rome II criteria. Overall, the median value of Asia IBS prevalences defined by various criteria ranges 6.5%-10.1%. With regard to gender difference, female predominance is usually found but not uniquely existed. For the IBS subtypes, the proportions of diarrhea predominant-IBS distribute widely from 0.8% to 74.0%, while constipation predominant-IBS proportion ranges 12%-77%. In conclusions, current Asia IBS prevalence is at least equal to the Western countries. Female predominant prevalence in Asia is common but not uniquely existed, while the proportions of IBS subtypes are too variable to find a rule.