Medical therapy has similar hemostatic efficacy with endoscopic treatment for PUB patients with adherent clot (FIIb ulcers).

BACKGROUND: Currently, there is no clear consensus on whether medical treatment or endoscopic treatment should be used for peptic ulcer bleeding patients with adherent clot. The aim of this study is to investigate the hemostatic effects of medical treatment, single endoscopic treatment, and combination endoscopic treatment for peptic ulcer bleeding (PUB) patients with adherent clot. METHODS: We retrospectively analyzed PUB patients with adherent clot who underwent endoscopic examination or treatment in our center from March 2014 to January 2023 and received intravenous administration of proton pump inhibitors. Patients were divided into medical treatment (MT) group, single endoscopic treatment (ST) group, and combined endoscopic treatment (CT) group. Subsequently, inverse probability of treatment weighting (IPTW) was performed to calculate the rebleeding rate. RESULTS: A total of 605 eligible patients were included in this study. After IPTW, the rebleeding rate in the MT group on days 3, 7, 14, and 30 were 13.3 (7.3), 14.2 (7.8), 14.5 (7.9), and 14.5 (7.9), respectively; the rebleeding rates in the ST group were 17.4 (5.1), 20.8 (6.1), 20.8 (6.1), and 20.8 (6.1), respectively; the rebleeding rates in the CT group were 0.4 (0.9), 1.7 (3.3), 2.3 (4.5), and 2.3 (4.5), respectively. Although the rebleeding rate in the medical treatment group was higher, there was no significant difference among the three groups on days 3, 7, 14, and 30 (P = 0.132, 0.442, 0.552, and 0.552). CONCLUSIONS: Medical therapy has similar hemostatic efficacy with endoscopic treatment for PUB patients with adherent clot (FIIb ulcers). However, for patients with more risk factors and access to well-equipped endoscopy centers, endoscopic treatment may be considered. The choice of treatment approach should be based on the individual conditions of the patient, as well as other factors such as medical resources available.

Epinephrine injection monotherapy shows similar hemostatic efficacy to epinephrine injection combined therapy in high-risk patients (Forrest Ib) with bleeding ulcers.

BACKGROUND: Whether combination therapy has higher hemostatic efficacy than epinephrine injection monotherapy in different Forrest classifications is not clear. This study aimed to compare hemostatic efficacy between epinephrine injection monotherapy (MT) and combination therapy (CT) based on different Forrest classifications. METHODS: We retrospectively analyzed peptic ulcer bleeding (PUB) patients who underwent endoscopic epinephrine injections or epinephrine injections combined with a second therapy between March 2014 and June 2022 in our center, and the patients were divided into MT group or CT group. Subsequently, a propensity score matching analysis (PSM) was performed and rebleeding rates were calculated according to Forrest classifications via a stratified analysis. RESULTS: Overall, 605 patients who met the inclusion criteria were included, and after PSM, 173 patients in each of the CT and MT groups were included. For PUB patients with nonbleeding visible vessels (FIIa), the rebleeding rates by Days 3, 7, 14, and 30 after PSM were 8.8%, 17.5%, 19.3%, and 19.3% in the MT group, respectively, and rates were 0%, 4.1%, 5.5%, and 5.5% in the CT group, respectively, with significant differences observed between the two groups by Days 3, 7, 14, and 30 (P = 0.015, P = 0.011, P = 0.014, and P = 0.014, respectively). However, for PUB patients with oozing bleeding (FIb), the rebleeding rates by Days 3, 7, 14, and 30 after PSM were 14.9%, 16.2%, 17.6%, and 17.6% in the MT group, respectively, and rates were 13.2%, 14.7%, 14.7%, and 16.2% in the CT group, respectively, with no significant differences observed between the two groups by Days 3, 7, 14, and 30 (P = 0.78, P = 0.804, P = 0.644 and P = 0.825). CONCLUSION: Combined therapy has higher hemostatic efficacy than epinephrine injection monotherapy for PUB patients with visible blood vessel (FIIa) ulcers. However, epinephrine injection monotherapy is equally as effective as combined therapy for PUB patients with oozing blood (FIb) ulcers.

Nomogram for predicting rebleeding after initial endoscopic epinephrine injection monotherapy hemostasis in patients with peptic ulcer bleeding: a retrospective cohort study.

BACKGROUND: Although the current guidelines recommend endoscopic combination therapy, endoscopic epinephrine injection (EI) monotherapy is still a simple, common and effective modality for treating peptic ulcer bleeding (PUB). However, the rebleeding risk after EI monotherapy is still high, and identifying rebleeding patients after EI monotherapy is unclear, which is highly important in clinical practice. This study aimed to identify risk factors and constructed a predictive nomogram related to rebleeding after EI monotherapy. METHODS: We consecutively and retrospectively analyzed 360 PUB patients who underwent EI monotherapy between March 2014 and July 2021 in our center. Then we identified independent risk factors associated with rebleeding after initial endoscopic EI monotherapy by multivariate logistic regression. A predictive nomogram was developed and validated based on the above predictors. RESULTS: Among all PUB patients enrolled, 51 (14.2%) had recurrent hemorrhage within 30 days after endoscopic EI monotherapy. After multivariate logistic regression, shock [odds ratio (OR) = 12.691, 95% confidence interval (CI) 5.129-31.399, p < 0.001], Rockall score (OR = 1.877, 95% CI 1.250-2.820, p = 0.002), tachycardia (heart rate > 100 beats/min) (OR = 2.610, 95% CI 1.098-6.203, p = 0.030), prolonged prothrombin time (PT > 13 s) (OR = 2.387, 95% CI 1.019-5.588, p = 0.045) and gastric ulcer (OR = 2.258, 95% CI 1.003-5.084, p = 0.049) were associated with an increased risk of rebleeding after an initial EI monotherapy treatment. A nomogram incorporating these independent high-risk factors showed good discrimination, with an area under the receiver operating characteristic curve (AUROC) of 0.876 (95% CI 0.817-0.934) (p < 0.001). CONCLUSIONS: We developed a predictive nomogram of rebleeding after EI monotherapy, which had excellent prediction accuracy. This predictive nomogram can be conveniently used to identify low-risk rebleeding patients after EI monotherapy, allowing for decision-making in a clinical setting.

Molecular testing for H. pylori clarithromycin and quinolone resistance: a prospective Chinese study.

In China, there is a high prevalence of antibiotic-resistant Helicobacter pylori infections in the population. The aim of the study was to assess a new ARMS-PCR test for detection of H. pylori clarithromycin resistance (CR) and quinolone resistance (QR) mutations and evaluate the spectrum of antibiotic resistance in patients from three Chinese provinces. Sanger sequencing and multiplex ARMS-PCR were used to detect H. pylori CR and QR bacteria in gastric biopsy samples. Among the 1,182 patients enrolled with gastritis, 643 (54.4%) were positive for H. pylori. Of these, 371 (57.7%) had antibiotic-resistant strains, comprising 236 (63.6%) with a single drug antibiotic-resistant strain and 135 (36.4%) with multiple drug-resistant strains. Following Sanger sequencing analysis of 23S rRNA and gyrA gene for mutations (antibiotic resistance markers), rates of CR, QR, and multidrug resistance (CR and QR) were 19.9, 12.0, and 25.8%, respectively. The 23S rRNA CR mutation A2143G (286, 96.9%) and the gyrA QR mutations C261A (85, 31.5%) and G271A (71, 26.3%) were common. Benchmarking against Sanger sequencing results, multiplex ARMS-PCR test had a high diagnostic sensitivity and specificity for detection of CR (96 and 93%), QR (95 and 92%) and multidrug resistance (95 and 95%). Based on our findings, the high incidence of single and multiple antibiotic resistance requires the routine checking of antibiotic resistance in all patients with suspected H. pylori infections. Multiplex ARMS-PCR is a simple and rapid test that can be now used for more efficient treatment of H. pylori infections and reduces the misuse of antibiotics.

Tolvaptan therapy of Chinese cirrhotic patients with ascites after insufficient diuretic routine medication responses: a phase III clinical trial.

BACKGROUND: To determine the safety and efficacy of different doses of tolvaptan for treating Chinese cirrhotic patients with or without hyponatraemia who still had ascites after routine therapy with diuretics. METHODS: In the present placebo-controlled, randomized, double-blinded, multicentre clinical trial, patients with cirrhotic ascites who failed to adequately respond to a combination of an aldosterone antagonist plus an orally administered loop diuretic were randomly placed at a 4:2:1 ratio into 3 groups [the 15 mg/day tolvaptan group (N = 301), 7.5 mg/day tolvaptan group (N = 153) and placebo group (N = 76)] for 7 days of treatment. The effects and safety were evaluated on days 4 and 7. A change in body weight from baseline on day 7 of treatment was the primary endpoint. RESULTS: The administration of 7.5 or 15 mg/day tolvaptan significantly decreased body weight from baseline on day 7 of treatment compared to that with placebo treatment (P = 0.026; P = 0.001). For the secondary endpoints, changes in abdominal circumference from baseline and improvements in ascites were markedly different in the treatment groups and the placebo group on day 7 (P7.5 = 0.05, P15.0 = 0.002 and P7.5 = 0.037, P15.0 = 0.003), but there was no difference between the 7.5 mg/day and 15 mg/day dosage groups. The 24-h cumulative urine volume was higher in the 7.5 mg/day and 15 mg/day tolvaptan groups than the placebo group (P = 0.002, P < 0.001) and was greater in the 15 mg/day tolvaptan group than the 7.5 mg/day tolvaptan group (P = 0.004). Sodium serum concentrations were higher in patients with hyponatraemia after tolvaptan treatment, with no significant difference between the two dosage groups. The incidence of serious adverse drug reactions was not different between the groups (P = 0.543). CONCLUSIONS: Tolvaptan treatment at 7.5 mg per day might be a good therapeutic choice for Chinese cirrhotic patients with ascites who did not achieve satisfactory clinical responses to previous treatment regimens with combination therapy with an aldosterone antagonist and an orally administered loop diuretic. TRIAL REGISTRATION: NCT01349348. Retrospectively registered May 2011.

Superoxide Dismutase Predicts Persistent Circulation Failure and Mortality in the Early Stage of Acute Pancreatitis.

OBJECTIVES: Oxidative stress is an important event in the pathogenesis of acute pancreatitis. Superoxide dismutase is a major antioxidant enzyme in the body. The aim of this study was to investigate the changes in superoxide dismutase activity early in the onset of acute pancreatitis and its value in predicting the risk of organ failure and mortality. METHODS: Data for 2549 patients hospitalized from 2013 to 2017 were extracted from the prospective database, and we selected 854 adult patients who were admitted within 24 h of disease onset with complete data. Serum superoxide dismutase activities on the first, second, and third days of hospital admission for patients with different severities, organ failure, and mortality were compared. The areas under the curve for the prediction of organ failure, pancreatic necrosis, and mortality were estimated using receiver operating characteristic curves. RESULTS: Among the 854 adult patients, superoxide dismutase activities were significantly different among patients with mild acute pancreatitis, moderately severe acute pancreatitis, and severe acute pancreatitis (P = 0.005). Superoxide dismutase activity was significantly decreased in patients with persistent renal failure (77.8 ± 37.2), persistent circulatory failure (66.2 ± 14.9), and mortality (64.3 ± 16.0). The accuracy of superoxide dismutase with regard to predicting persistent circulatory failure and mortality was high, and the areas under the receiver operating characteristic curves were 0.83 and 0.84, respectively. CONCLUSIONS: Superoxide dismutase activity was negatively correlated with the severity and clinical outcome of AP. Superoxide dismutase activity is highly accurate at predicting persistent circulation failure and mortality in the early stage of AP.

Development and validation of a prediction rule for estimating gastric cancer risk in the Chinese high-risk population: a nationwide multicentre study.

OBJECTIVE: To develop a gastric cancer (GC) risk prediction rule as an initial prescreening tool to identify individuals with a high risk prior to gastroscopy. DESIGN: This was a nationwide multicentre cross-sectional study. Individuals aged 40-80 years who went to hospitals for a GC screening gastroscopy were recruited. Serum pepsinogen (PG) I, PG II, gastrin-17 (G-17) and anti-Helicobacter pylori IgG antibody concentrations were tested prior to endoscopy. Eligible participants (n=14 929) were randomly assigned into the derivation and validation cohorts, with a ratio of 2:1. Risk factors for GC were identified by univariate and multivariate analyses and an optimal prediction rule was then settled. RESULTS: The novel GC risk prediction rule comprised seven variables (age, sex, PG I/II ratio, G-17 level, H. pylori infection, pickled food and fried food), with scores ranging from 0 to 25. The observed prevalence rates of GC in the derivation cohort at low-risk (≤11), medium-risk (12-16) or high-risk (17-25) group were 1.2%, 4.4% and 12.3%, respectively (p<0.001).When gastroscopy was used for individuals with medium risk and high risk, 70.8% of total GC cases and 70.3% of early GC cases were detected. While endoscopy requirements could be reduced by 66.7% according to the low-risk proportion. The prediction rule owns a good discrimination, with an area under curve of 0.76, or calibration (p<0.001). CONCLUSIONS: The developed and validated prediction rule showed good performance on identifying individuals at a higher risk in a Chinese high-risk population. Future studies are needed to validate its efficacy in a larger population.

PRSS23 knockdown inhibits gastric tumorigenesis through EIF2 signaling.

PRSS23 is a newly discovered serine protease that has been associated with tumor progression in various types of cancers. Our previous study showed PRSS23 is down-regulated obviously in Hedgehog pathway blocked gastric cancer cells. However, the correlation between PRSS23 and tumor progression of gastric cancer remains unclear. Here, the role and mechanism of PRSS23 in tumor progression of gastric cancer were determined. PRSS23 protein levels were significantly increased in gastric cancer tissues compared with the paired adjacent normal gastric mucosa tissues. The high expression of PRSS23 correlated strongly with both poor differentiated histology and cancer region of sinus ventriculi. Gastric cancer patients with low PRSS23 expression displayed a better prognosis. In gastric cancer cells, PRSS23 knockdown inhibited cell proliferation and induced apoptosis. In xenograft tumor model, PRSS23 knockdown led to dramatic decreases of the average tumor volume and the average tumor weight. In addition, PRSS23 knockdown suppressed gastric cancer growth through inhibiting EIF2 signaling using gene expression microarray analysis. Taken together, our results suggest PRSS23 is highly associated with human gastric tumorigenesis and progression. PRSS23 knockdown could suppress tumor growth of gastric cancer in vitro and in vivo through inhibiting EIF2 signaling, and EIF4E maybe a potential target of PRSS23. PRSS23 could serve as a potential target for gastric cancer therapy, and also a biomarker for the prediction of prognosis of gastric cancer.

The efficacy of oral Zhizhu Kuanzhong, a traditional Chinese medicine, in patients with postprandial distress syndrome.

BACKGROUND AND AIM: The treatment of patients with functional dyspepsia (FD) remains unsatisfactory. We assessed the efficacy of Zhizhu Kuanzhong (ZZKZ) capsule, a traditional Chinese medicine formula, in patients with postprandial distress syndrome (PDS) of FD. METHODS: The study was designed as a multicenter, randomized, double-blinded, controlled clinical trial. Three-hundred ninety-two patients with PDS defined by Rome III criteria from 16 centers in China were randomly assigned to receive either ZZKZ or placebo. The proportion of the responders at 4 weeks after randomization was considered primary endpoint. Secondary endpoint was the symptom score reduction of each dyspeptic symptom relative to the baseline at 4 weeks after randomization in all subjects. RESULTS: In terms of the primary endpoint, the proportion of the responders concerning the composite PDS symptom score was 38.8% and 54.7% in placebo group and ZZKZ group, respectively (P = 0.003), in per protocol analysis at 4 weeks after randomization. Concerning the individual evaluated upper gastrointestinal symptoms, only postprandial fullness and early satiety showed significant difference in symptom score reduction at 4 weeks after randomization between placebo and ZZKZ groups. CONCLUSIONS: Zhizhu Kuanzhong is superior to placebo in the treatment of PDS with FD. The exact mechanisms by which ZZKZ improves symptoms remain to be established (http://www.chictr.org.cn/ChinCTR-TRC-14004714).

Ten-Day Quadruple Therapy Comprising Low-Dose Rabeprazole, Bismuth, Amoxicillin, and Tetracycline Is an Effective and Safe First-Line Treatment for Helicobacter pylori Infection in a Population with High Antibiotic Resistance: a Prospective, Multicenter, Randomized, Parallel-Controlled Clinical Trial in China.

The objective of this study was to investigate the efficacy and safety of 10-day bismuth quadruple therapy with amoxicillin, tetracycline, or clarithromycin and different doses of rabeprazole for first-line treatment of Helicobacter pylori infection. This multicenter, randomized, parallel-controlled clinical trial was conducted between March 2013 and August 2014. A total of 431 H. pylori-infected patients with duodenal ulcers were enrolled and randomized into four treatment groups (1:1:1:1) for 10 days, as follows: (i) a group receiving a low dose of rabeprazole of 10 mg twice a day (b.i.d.) (LR dose) plus bismuth, amoxicillin, and clarithromycin (LR-BAC); (ii) a group receiving LR plus bismuth, amoxicillin, and tetracycline (LR-BAT); (iii) a group receiving a high dose of rabeprazole of 20 mg b.i.d. (HR dose) plus bismuth, amoxicillin, and clarithromycin (HR-BAC); and (iv) a group receiving HR-BAT. Antimicrobial susceptibility was assessed by the Etest method. The primary outcome was H. pylori eradication at 4 weeks after the treatment. The per-protocol (PP) eradication rates in the LR-BAC, LR-BAT, HR-BAC, and HR-BAT groups were 94.1%, 91.9%, 94.8%, and 91.9%, respectively, while the intention-to-treat (ITT) eradication rates in those groups were 87.2%, 87.2%, 87.7%, and 86%, respectively. There was no significant difference between the four groups in PP analysis (P = 0.799) and ITT analysis (P = 0.985). The efficacies of four-treatment therapy were not affected by antibiotic resistance. The adverse events in the four treatment groups were similar; central nervous system (CNS) and gastrointestinal symptoms were the most common reported. Bismuth-containing quadruple therapy with low-dose rabeprazole, amoxicillin, and tetracycline is a good option for first-line treatment of H. pylori infection in a population with high antibiotic resistance. (This study is registered at Chinese Clinical Trials Registry [www.chictr.org.cn] under number ChiCTR1800014832.).

New single capsule of bismuth, metronidazole and tetracycline given with omeprazole versus quadruple therapy consisting of bismuth, omeprazole, amoxicillin and clarithromycin for eradication of Helicobacter pylori in duodenal ulcer patients: a Chinese prospective, randomized, multicentre trial.

Objectives: To assess the efficacy and safety of omeprazole given with the new single capsule of bismuth, metronidazole and tetracycline (OBMT) compared with quadruple treatment consisting of omeprazole, bismuth, amoxicillin and clarithromycin (OBAC) for Helicobacter pylori eradication in duodenal ulcer patients. Methods: This single-blind, randomized multicentre trial was conducted in 10 tertiary hospitals in China between January 2013 and April 2014. Patients were randomized to receive 10 days of OBMT therapy or 10 days of OBAC therapy. Our primary outcome was the H. pylori eradication rate, confirmed by negative [13C]urea breath tests 20-25 days after the end of omeprazole maintenance. Antibiotic resistance was determined by Etest. This study is registered with ClinicalTrials.gov, number ChiCTR-TRC-13003143. Results: One hundred and ninety-two patients received OBMT therapy and 192 received OBAC therapy. There was no significant difference between the eradication rates achieved by OBMT and OBAC in either the ITT analysis (86.46% versus 87.50%, P = 0.762) or the PP analysis (94.58% versus 93.06%, P = 0.563). The efficacies of OBMT and OBAC were not affected by metronidazole or clarithromycin resistance. Treatment-emergent adverse events (TEAEs) for both treatments were similar; gastrointestinal and CNS symptoms were the most commonly reported. Conclusions: The new single-capsule OBMT quadruple therapy is as effective and well tolerated as the widely used OBAC therapy for treatment of H. pylori in clinical practice in China. In addition, this OBMT therapy largely overcomes H. pylori metronidazole and clarithromycin resistance.

Cutting Edge: Expression of IRF8 in Gastric Epithelial Cells Confers Protective Innate Immunity against Helicobacter pylori Infection.

IFN regulatory factor 8 (IRF8) is expressed in many types of blood cells and plays critical roles in cellular differentiation and function. However, the role of IRF8 in nonhematopoietic systems remains poorly understood. In this study, we provide evidence that IRF8 is a transcriptional modulator of the gastric mucosa necessary for limiting Helicobacter pylori colonization. H. pylori infection significantly upregulated expression of IRF8, which, in turn, promoted IFN-γ expression by gastric epithelial cells. Mice deficient in IRF8 exhibited increased H. pylori colonization and aborted induction of mucosal IFN-γ. Genome-wide analyses of IFN-γ-treated gastric epithelial cells by chromatin immunoprecipitation sequencing and RNA sequencing led to the identification of IRF8 target genes, with many belonging to the IFN-regulated gene family that was observed previously in immune cells. Our results identify the IRF8-IFN-γ circuit as a novel gastric innate immune mechanism in the host defense against infection with H. pylori.

Clinical characteristics of acute pancreatitis in pregnancy: experience based on 121 cases.

PURPOSE: Acute pancreatitis in pregnancy (APIP) is a rare condition; however, it markedly affects maternal and fetal health. This study aimed to describe the types, clinical characteristics, mortality, and the safety and necessity of gestation termination of acute pancreatitis in pregnancy (APIP). METHODS: We retrospectively reviewed 121 APIP cases in the Gastroenterology Department of The First Affiliated Hospital of Nanchang University. APIP diagnosis were based on 2012 Atlanta Criteria. The correlation between APIP types, severity, biochemical parameters and mortality was analyzed. RESULTS: The most common symptoms for APIP were abdominal pain (86.8%) and vomiting (73.6%). The most common causes for APIP were gallstone (36.4%) and hypertriglyceridemia (32.2%) and hypertriglyceridemic APIP was correlated with a higher rate for local complication (P = 0.012). Serum calcium level was negatively correlated with the severity of APIP (P < 0.01). The overall maternal and fetal mortality rate were 3.3% (4/121) and 11.6% (14/121), respectively. The severity of APIP was significantly correlated with higher risks for maternal and fetal death (P < 0.01). 72.7% of moderate-to-severe APIP patients underwent Cesarean section to terminate gestation safely. CONCLUSION: The most common causes of APIP were gallstone and hypertriglyceridemia. Lower level of serum calcium could be used as an indicator for the severity of the APIP. The severity of APIP was associated with higher risk for neonate asphyxia, and maternal and fetal death.

Double-catheter lavage combined with percutaneous flexible endoscopic debridement for infected pancreatic necrosis failed to percutaneous catheter drainage.

BACKGROUND: Infected pancreatic necrosis (IPN) is a serious local complication of acute pancreatitis, with high mortality. Minimally invasive therapy including percutaneous catheter drainage (PCD) has become the preferred method for IPN instead of traditional open necrosectomy. However, the efficacy of double-catheter lavage in combination with percutaneous flexible endoscopic debridement after PCD failure is unknown compared with surgical necrosectomy. METHODS: A total of 27 cases of IPN patients with failure PCD between Jan 2014 and Dec 2015 were enrolled in this retrospective cohort study. Fifteen patients received double-catheter lavage in combination with percutaneous flexible endoscopic debridement, and 12 patients underwent open necrosectomy. The primary endpoint was the composite end point of major complications or death. The secondary endpoint included mortality, major complication rate, ICU admission length of stay, and overall length of stay. RESULTS: The primary endpoint occurrence rate in double-catheter lavage in combination with percutaneous flexible endoscopic debridement group (8/15, 53%) was significantly lower than that in open necrosectomy group (11/12, 92%) (RR = 1.71, 95% CI = 1.04 - 2.84, P < 0.05). Though the mortality between two groups showed no statistical significance (0% vs. 17%, P = 0.19), the rate of new-onset multiple organ failure and ICU admission length of stay in the experimental group was significantly lower than that in open necrosectomy group (13% vs. 58%, P = 0.04; 0 vs. 17, P = 0.02, respectively). Only 40% of patients required ICU admission after percutaneous debridement, which was markedly lower than the patients who underwent surgery (83%; P < 0.05). CONCLUSIONS: Double-catheter lavage in combination with percutaneous flexible endoscopic debridement showed superior effectiveness, safety, and convenience in patients with IPN after PCD failure as compared to open necrosectomy.

Value of Raw Rhubarb Solution in the Precaution of Post-endoscopic Retrograde Cholangiopancreatography Pancreatitis in Patients with High-Risk Factors: A Predictive Random Compared Research in One Center.

BACKGROUND AND AIMS: Post-ERCP pancreatitis and hyperamylasemia are common complications of endoscopic retrograde cholangiopancreatography (ERCP), especially in high-risk patients. The aim of this study is to evaluate whether a raw rhubarb solution can reduce the incidence of PEP and post-ERCP hyperamylasemia. METHODS: From October 2012 to October 2013, 2100 patients received ERCP in our Endoscopic Center. Five hundred patients with high-risk factors were enrolled randomly into the raw rhubarb group (RG, 250 cases drank a raw rhubarb soak solution per 3 h until defecation after ERCP) and the control group (CG, 250 cases drank water after ERCP) in the study. The serum amylase concentration was measured. The abdominal pain, purge time and symptoms of patients were observed in the two groups. RESULTS: There were no differences in patient demographics, medical history, ERCP procedure, and patient- and procedure-related high-risk factors between the two groups. PEP incidence was 2% (5/250) in the RG group, which was lower than that in the CG group (7.6%, 19/250) (P < 0.01). The rate of post-ERCP hyperamylasemia was 5.2% (13/250) and 16.8% (42/250) in the RG group and CG group, respectively. The incidence of hyperamylasemia in the RG group was significantly lower than that in the CG group (P < 0.01). The incidence of abdominal pain 24 h after ERCP in the RG group was lower than that in the CG group (P < 0.01). No side effects were observed for raw rhubarb solution. CONCLUSIONS: A raw rhubarb solution is safe and effective in preventing the incidence of PEP and hyperamylasemia in high-risk patients.

LKB1/AMPK inhibits TGF-ß1 production and the TGF-ß signaling pathway in breast cancer cells.

Adenosine monophosphate-activated protein kinase (AMPK) acts as a fuel gauge that maintains energy homeostasis in both normal and cancerous cells, and has emerged as a tumor suppressor. The present study aims to delineate the functional relationship between AMPK and transforming growth factor beta (TGF-ß). Our results showed that expression of liver kinase B1 (LKB1), an upstream kinase of AMPK, impeded TGF-ß-induced Smad phosphorylation and their transcriptional activity in breast cancer cells, whereas knockdown of LKB1 or AMPKα1 subunit by short hairpin RNA (shRNA) enhanced the effect of TGF-ß. Furthermore, AMPK activation reduced the promoter activity of TGF-ß1. In accordance, type 2 diabetic patients taking metformin displayed a trend of reduction of serum TGF-ß1, as compared with those without metformin. A significant reduction of serum TGF-ß1 was found in mice after treatment with metformin. These results suggest that AMPK inhibits the transcription of TGF-ß1, leading to reduction of its concentration in serum. Finally, metformin suppressed epithelial-to-mesenchymal transition of mammary epithelial cells. Taken together, our study demonstrates that AMPK exerts multiple actions on TGF-ß signaling and supports that AMPK can serve as a therapeutic drug target for breast cancer.

Emergent Triglyceride-lowering Therapy With Early High-volume Hemofiltration Against Low-Molecular-Weight Heparin Combined With Insulin in Hypertriglyceridemic Pancreatitis: A Prospective Randomized Controlled Trial.

OBJECTIVES: To compare the value of emergent triglyceride (TG)-lowering therapies between early high-volume hemofiltration (HVHF) and low-molecular-weight heparin (LMWH) combined with insulin (LMWH+insulin) as well as their effects on the outcomes of hypertriglyceridemic pancreatitis (HTGP) patients. METHODS: In this randomized controlled trial, 66 HTGP patients presenting within 3 days after the onset of symptoms from August 2011 to October 2013 were assigned randomly to receive either HVHF or LMWH+insulin as an emergent TG-lowering therapy. Thirty-three patients were included in each group, and the therapy was started as soon as possible after admission. TG levels, clinical outcomes, and inflammatory biomarkers were compared between the 2 groups. RESULTS: Thirty-two individuals in the HVHF group and 34 in the LMWH+insulin group were included in the final analysis. Characteristics of the patients in both groups were roughly comparable. HVHF could remove TG from the plasma and achieve its target (<500 mg/dL) in approximately 9 hours, whereas the target was not achieved within 48 hours in patients receiving the LMWH+insulin treatment (P<0.05). However, no differences were found in terms of the majority of the clinical outcomes, including local pancreatic complications (P>0.05), the requirement of surgical intervention (P=0.49), mortality (P=0.49), and the duration of hospitalization (P=0.144). Furthermore, an unexpectedly higher incidence of persistent organ failure was observed in the HVHF group compared with the LMWH+insulin group (risk ratio with HVHF, 2.42; 95% confidence interval, 1.15-5.11; P=0.01). Hospital charges for patients in the HVHF group were approximately 2-fold higher than those for patients in the LMWH+insulin group (5.20±4.90 vs. 2.92±3.21, P=0.03). We selected a systemic inflammatory response syndrome score of at least 2 at baseline as a predictor of SAP patients, and the subgroup analyses showed that HVHF cannot improve the prognosis of the predicted SAP patients compared with the LMWH+insulin group. CONCLUSIONS: HVHF can lower TG levels more efficiently than LMWH+insulin therapy, but it is not superior in terms of clinical outcomes and costs. Further multicenter studies with large samples are required to clarify the feasibility of administering the HVHF treatment to HTGP patients (ChiCTR-TRC-13003274).

AMPK Inhibits the Stimulatory Effects of TGF-ß on Smad2/3 Activity, Cell Migration, and Epithelial-to-Mesenchymal Transition.

AMP-activated protein kinase (AMPK), an important downstream effector of the tumor suppressor liver kinase 1 (LKB1) and pharmacologic target of metformin, is well known to exert a preventive and inhibitory effect on tumorigenesis; however, its role in cancer progression and metastasis has not been well characterized. The present study investigates the potential roles of AMPK in inhibiting cancer-cell migration and epithelial-to-mesenchymal transition (EMT) by regulating the canonical transforming growth factor ß (TGF-ß) signaling pathway, an important promoting factor for cancer progression. Our results showed that activation of AMPK by metformin inhibited TGF-ß-induced Smad2/3 phosphorylation in cancer cells in a dose-dependent manner. The effect of metformin is dependent on the presence of LKB1. A similar effect was obtained by expressing a constitutive active mutant of AMPKα1 subunit, whereas the expression of a dominant negative mutant of AMPKα1 or ablation of AMPKα subunits greatly enhanced TGF-ß stimulation of Smad2/3 phosphorylation. As a consequence, expression of genes downstream of Smad2/3, including plasminogen activator inhibitor-1, fibronectin, and connective tissue growth factor, was suppressed by metformin in a LKB1-dependent fashion. In addition, metformin blocked TGF-ß-induced inteleukin-6 expression through both LKB1-dependent and -independent mechanisms. Our results also indicate that activation of LKB1/AMPK inhibits TGF-ß-stimulated cancer cell migration. Finally, TGF-ß induction of EMT was inhibited by phenformin and enhanced by knockdown of LKB1 expression with shRNA. Together, our data suggest that AMPK could be a drug target for controlling cancer progression and metastasis.

Single-channel endoscopic closure of large endoscopy-related perforations.

BACKGROUND AND STUDY AIMS: Gastrointestinal endoscopy procedures, such as endoscopic retrograde cholangiopancreatography (ERCP), endoscopic submucosal dissection (ESD), and colonoscopy are widely used for the diagnosis or treatment of digestive diseases. Perforation is a rare but potentially lethal complication. Large perforations usually require immediate endoscopic or surgical repair. Endoscopic closure using a nylon loop pouch suture is usually performed with a double-channel endoscope. This paper describes the endoscopic closure of large procedure-related perforations using a single-channel endoscope. PATIENTS AND METHODS: A total of 10 patients with large perforations (2.5 - 4.0 cm), which occurred during ERCP, ESD, or colonoscopy, were treated using the single-channel endoscope technique. RESULTS: All perforations were successfully closed using a nylon loop pouch suture through the single-channel endoscope. No surgery or further endoscopic intervention was required. CONCLUSIONS: Nylon loop pouch suture through a single-channel endoscope was easy to perform and was feasible for the closure of large gastrointestinal perforations.

Prophylactic somatostatin can reduce incidence of post-ERCP pancreatitis: multicenter randomized controlled trial.

BACKGROUND AND STUDY AIM: Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) remains the most common complication of ERCP. Somatostatin may inhibit pancreatic secretion and has been tested for PEP prophylaxis. However, the results of previous studies are inconsistent. The aim of the current study was to investigate whether somatostatin can reduce the incidence of PEP. PATIENTS AND METHODS: The study was a multicenter, open-label, randomized controlled trial. A total of 908 patients with normal amylase levels who were undergoing ERCP were randomized to receive somatostatin 250 µg bolus injection before ERCP and 250 µg/hour intravenous infusion for 11 hours after ERCP (somatostatin group) or no somatostatin treatments (control group). The incidences of PEP and hyperamylasemia were compared in the two groups. RESULTS: The full analysis set included 900 patients (445 in the somatostatin group, 455 in the control group). PEP developed in 34 patients (7.5 %) in the control group (95 % confidence interval [CI] 5.4 % - 10.3 %) and in 18 patients (4.0 %) in the somatostatin group (95 %CI 2.6 % - 6.3 %; P = 0.03). Hyperamylasemia occurred in 46 patients (10.1 %) in the control group (95 %CI 7.7 % - 13.2 %) and in 27 patients (6.1 %) in the somatostatin group (95 %CI 4.2 % - 8.7 %; P = 0.03). No perforation or death occurred during the study. CONCLUSIONS: This study showed that somatostatin was effective and safe for the prevention of PEP and hyperamylasemia in ERCP patients.(ClinicalTrials.gov number, NCT01431781).