Wence Zhou

Routine pre-procedural rectal indometacin versus selective post-procedural rectal indometacin to prevent pancreatitis in patients undergoing endoscopic retrograde cholangiopancreatography: a multicentre, single-blinded, randomised controlled trial.

BACKGROUND Rectal indometacin decreases the occurrence of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). However, the population most at risk and the optimal timing of administration require further investigation. We aimed to assess whether pre-procedural administration of rectal indometacin in all patients is more effective than post-procedural use in only high-risk patients to prevent post-ERCP pancreatitis. METHODS We did a multicentre, single-blinded, randomised controlled trial at six centres in China. Eligible patients with native papilla undergoing ERCP were randomly assigned in a 1:1 ratio (with a computer-generated list) to universal pre-procedural indometacin or post-procedural indometacin in only high-risk patients, with stratification by trial centres and block size of ten. In the universal indometacin group, all patients received a single dose (100 mg) of rectal indometacin within 30 min before ERCP. In the risk-stratified, post-procedural indometacin group, only patients at predicted high risk received rectal indometacin, immediately after ERCP. Investigators, but not patients, were masked to group allocation. The primary outcome was overall ocurrence of post-ERCP pancreatitis. The analysis followed the intention-to-treat principle. This study was registered with ClinicalTrials.gov, number NCT02002650. FINDINGS Between Dec 15, 2013, and Sept 21, 2015, 2600 patients were randomly assigned to universal, pre-procedural indometacin (n=1297) or risk-stratified, post-procedural indometacin (n=1303). Overall, post-ERCP pancreatitis occurred in 47 (4%) of 1297 patients assigned to universal indometacin and 100 (8%) of 1303 patients assigned to risk-stratified indometacin (relative risk 0·47; 95% CI 0·34-0·66; p<0·0001). Post-ERCP pancreatitis occurred in 18 (6%) of 305 high-risk patients in the universal group and 35 (12%) of 281 high-risk patients in the risk-stratified group (p=0·0057). Post-ERCP pancreatitis was also less frequent in average-risk patients in the universal group (3% [29/992]), in which they received indometacin, than in the risk-stratified group (6% [65/1022]), in which they did not receive the drug (p=0·0003). Other than pancreatitis, adverse events occurred in 41 (3%; two severe) patients in the universal indometacin group and 48 (4%; one severe) patients in the risk-stratified group. The most common adverse events were biliary infection (22 [2%] patients vs 33 [3%] patients) and gastrointestinal bleeding (13 [1%] vs ten [1%]). INTERPRETATION Compared with a risk-stratified, post-procedural strategy, pre-procedural administration of rectal indometacin in unselected patients reduced the overall occurrence of post-ERCP pancreatitis without increasing risk of bleeding. Our results favour the routine use of rectal indometacin in patients without contraindications before ERCP. FUNDING National Key Technology R&D Program, National Natural Science Foundation of China.

Risk factors for postendoscopic retrograde cholangiopancreatography pancreatitis: a retrospective analysis of 7,168 cases.

BACKGROUND AND AIMS Postendoscopic retrograde cholangiopancreatography pancreatitis (PEP) is one of the most common and serious complications after endoscopic retrograde cholangiopancreatography (ERCP). This study aims to test the hypothesis that the incidence of PEP declined over time due to improved patient selection and/or endoscopic equipment and endoscopic techniques. Therefore, we compared the incidence and risk factors of PEP between four arbitrary chronologically stratified groups. METHODS A total of 7,168 cases of ERCP procedures were retrospectively analyzed. According to the different developmental stages of ERCP equipment and techniques, cases were divided into four groups. The incidence rates and major risk factors for acute PEP were compared between groups. RESULTS Among the 7,168 cases, the overall incidence of PEP was 3.70% (265/7,168). When analyzed against each stage of ERCP development, the incidence of PEP was 4.09% (77/1,884) in stage I, 5.79% (86/1,489) in stage II, 3.95% (62/1,568) in stage III and 1.80% (40/2,227) in stage IV. By univariate analysis, pancreatic stent placement (OR: 0.300) and use of propofol-balanced anesthesia (OR: 0.632) seem to be protective factors for acute PEP. By multivariate analysis, the following risk factors for PEP could be identified: repeated cannulation (OR: 3.462), pancreatic duct injection (OR: 3.218), balloon dilation of biliary sphincter (OR: 2.847), papillae precut (OR: 2.493), nonselective high-pressure injection (OR: 1.428), excessive electrocoagulation incision (OR: 1.263), history of pancreatitis (OR: 3.843) and suspected sphincter of Oddi dysfunction (OR: 1.782). CONCLUSIONS Improved technical procedures were associated with a significant reduction in the incidence of PEP. Risks for developing PEP may be minimized by constant improvement in ERCP techniques, such as routine use of a guidewire, highly selective cannulation, pancreatic stent placement and cautious incision.

Cyclooxygenase-2 −765 G/C polymorphisms and susceptibility to hepatitis B-related liver cancer in Han Chinese population

To investigate the relationship of cyclooxygenase-2 (COX-2) polymorphisms [COX-2 −765 G/C (rs 20417)] and susceptibility to hepatitis B-related liver cancer in Han Chinese population. The polymorphisms of COX-2 −765 G/C was detected by polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) in 300 patients with hepatitis B, 300 patients with cirrhosis, 300 patients with primary liver carcinoma and 300 health controls. The COX-2 −765 G/C genotypes were GG, GC and CC. There frequencies in the hepatitis B patients were 80.33, 17.67 and 2.00%; in the cirrhosis patients were 77.67, 18.00 and 4.33%; in the patients with primary liver carcinoma were 65.67, 28.33 and 6.00% and in the heathy controls were 87.00, 12.33 and 0.67%, respectively, COX-2 −765 C allele carriers had an increased risk of hepatitis B-related liver cancer. COX-2 −765 C allele carriers having drinking history or family history of liver cancer had higher risk for HCC. COX-2 −765 C allele genotype, drinking history and family history of liver cancer may increase the susceptibility to hepatitis B-related liver cancer in Gansu province, China.

Three initial diets for management of mild acute pancreatitis: A meta-analysis

AIM To compare non-liquid and clear-liquid diets, and to assess whether the latter is the optimal treatment for mild acute pancreatitis. METHODS The Cochrane Library, PUBMED, EMBASE, EBM review databases, Science Citation Index Expanded, and several Chinese databases were searched up to March 2011. Randomized controlled trials (RCTs) that compared non-liquid with clear-liquid diets in patients with mild acute pancreatitis were included. A meta-analysis was performed using available evidence from RCTs. RESULTS Three RCTs of adequate quality involving a total of 362 participants were included in the final analysis. Compared to liquid diet, non-liquid diet significantly decreased the length of hospitalization [mean difference (MD): 1.18, 95% CI: 0.82-1.55; P﹤0.00001] and total length of hospitalization (MD: 1.31, 95% CI: 0.45-2.17; P = 0.003). The subgroup analysis showed solid diet was more favorable than clear liquid diet in the length of hospitalization, with a pooled MD being -1.05 (95% CI: -1.43 to -0.66; P﹤0.00001). However, compared with clear liquid diet, both soft and solid diets did not show any significant differences for recurrence of pain after re-feeding, either alone [relative risk (RR): 0.95; 95% CI: 0.51-1.87; P = 0.88] and (RR: 1.22; 95% CI: 0.69-2.16; P = 0.49), respectively, or analyzed together as non-liquid diet (RR: 0.80; 95% CI: 0.47-1.36; P = 0.41). CONCLUSION The non-liquid soft or solid diet did not increase pain recurrence after re-feeding, compared with the clear-liquid diet. The non-liquid diet reduced hospitalization.

Silencing Alpha-Fetoprotein Inhibits VEGF and MMP-2/9 Production in Human Hepatocellular Carcinoma Cell

Alpha-fetoprotein not only serves as a diagnostic marker for liver cancer, but also posses a variety of biological functions. However, the role of Alpha-fetoprotein on tumor angiogenesis and cell invasion remains incompletely understood. In this study, we aimed to evaluate if Alpha-fetoprotein can regulate the major angiogenic factors and matrix metalloproteinases in human liver cancer cells. Alpha-fetoprotein silencing was achieved by Stealth RNAi. Expression of Alpha-fetoprotein was examined by a full-automatic electrochemistry luminescence immunity analyzer. Expression of VEGF, VEGFR-2, MMP-9, and MMP-2 was examined by Western blot and immunocytochemistry. Apoptosis was detected by TUNEL assay. Angiogenesis was detected by in vitro angiogenesis assay kit. Silencing of Alpha-fetoprotein led to an increased apoptosis, which was associated with a decreased expression of vascular endothelial growth factor, vascular endothelial growth factor receptor 2, matrix metalloproteinases-2/9. These results suggest that Alpha-fetoprotein may play a regulatory role on angiogenesis and cell invasion during liver cancer development.

Effect of CCNB1 silencing on cell cycle, senescence, and apoptosis through the p53 signaling pathway in pancreatic cancer: ZHANG et al.

Pancreatic cancer (PC) is a serious malignancy with high mortality and poor prognosis due to nonspecific incipient symptoms and early metastasis. Also, increasing evidence indicates that a panel of genes is newly identified in the pathogenesis of PC. As is a regulatory subunit, elevated cyclin B1 (CCNB1) expression has been detected in different cancers including PC. This study is designed to investigate the effects of CCNB1 silencing on cell cycle, senescence, and apoptosis through the p53 signaling pathway in PC. PC tissues and normal pancreatic tissues were collected. Cells were transfected and assigned into different groups. The expressions of CCNB1, p53, MDM2, Bax, caspase‐9, caspase‐3, and p21 in tissues and cells were detected by reverse transcription quantitative polymerase chain reaction and western blot analysis. β‐Galactosidase staining, MTT assay, and flow cytometry were conducted to test cell senescence, proliferation, cell cycle, and apoptosis. PC tissues showed higher expressions of CCNB1 and MDM2 and lower expressions of Bax, caspase‐9, caspase‐3, and p21. Cells transfected with shCCNB1 had lower expressions of CCNB1 and MDM2, whereas higher expressions of Bax, caspase‐9, caspase‐3, p53, and p21. The shCCNB1 group had decreased proliferation and S‐phase cell proportion and increased apoptosis, senescence, and G0/G1‐phase cell proportion. The PFT‐α group showed higher expressions of MDM2 and lower expressions of Bax, caspase‐9, caspase‐3, p53, and p21. The PFT‐α group had increased proliferation and S‐phase cell proportion and declined apoptosis, senescence, and G0/G1‐phase cell proportion. CCNB1 silencing inhibits cell proliferation and promotes cell senescence via activation of the p53 signaling pathway in PC.

Emergent Endoscopic Retrograde Cholangiopancreatography with Placement of Biliary Double Stents to Salvage Endoscopic Retrograde Cholangiopancreatography-Induced Stapfer's Type II Perforation

To the Editor: Endoscopic retrograde cholangiopancreatography (ERCP) plays a vital role in the management of pancreaticobiliary diseases in recent years and it concomitantly carries a risk of complications including post‐ERCP pancreatitis, cholangitis, bleeding, and perforation. The incidence of primary post‐ERCP complications ranges from 5.4% to 23.0%, and ERCP‐induced perforation can occur in 0.3–1.0% of cases, but the associated mortality is high ranging from 8% to 23%.[1] Because of the confluence of the bile duct and pancreatic duct meet at the papilla in proximity to the site of perforation in the duodenum, there is a potential risk of leakage of bile and pancreatic juice into the retroperitoneal space or peritoneum. Patients with Stapfer’s Type II perforation (perivaterian perforation) generally suffered from systemic inflammatory response syndrome, which could progress rapidly to acute lung injury and acute renal insufficiency and even multiple organ failure. All of these contribute to the significantly high mortality. A timely recognition and appropriate treatment are crucial to the management of ERCP‐induced perforation to reduce the overall mortality. Conventionally, surgery remains the primary treatment for iatrogenic perforations. With the improvement in endoscopic technique and development of new accessories, nonsurgical management with endoscopic treatment of perforation is increasingly being reported.[2] We report a retrospective analysis of ERCP‐induced Stapfer’s Type II perforations over a 5‐year period managed with nonsurgical approach combined with salvage ERCP.

Narrow band imaging helps identify the ectopic opening of the common bile duct during endoscopic retrograde cholangiopancreatography

The ectopic opening of the common bile duct (CBD) into the stomach and pyloric canal is extremely rare, and it accounts for a mere 0.43% of patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) (1); however, when present, it often makes it difficult to recognize the papilla during endoscopy. Here we present a case where narrow band imaging (NBI) was used to discover an ectopic opening of the CBD.

Intermediate-stage hepatocellular carcinoma patients with a high Hbv-dna load may benefit from postoperative anti-hepatitis B virus therapy

Abstract Liver resection may be beneficial in intermediate-stage hepatocellular carcinoma (HCC), though the benefit of postoperative anti-hepatitis B virus (HBV) therapy in these patients remains unclear. In this study, we sought to evaluate the efficacy of postoperative anti-HBV for intermediate-stage HCC patients who underwent radical liver resection. According to inclusion and exclusion criteria, this study enrolled 202 HCC patients who underwent liver resection and had a high HBV-DNA load. The patients were divided into 2 groups on the basis of postoperative anti-HBV therapy: group A included patients undergoing postoperative anti-HBV therapy, whereas group B patients did not receive any postoperative anti-HBV therapy. Factors including baseline demographics, tumor characteristics, overall long-term survival, tumor-free survival, and tumor recurrence rate were compared between the 2 groups. Moreover, univariate and multivariate analyses were used to identify risk factors of HCC recurrence. Baseline demographics and tumor characteristics were comparable between the groups. The 1-, 3-, and 5-year overall survival rates in group A were 91.3%, 80.9%, and 66.1%, respectively, values that were significantly increased compared with group B (91.7%, 60.7%, and 52.4%, respectively, P = .019). Group A patients also exhibited enhanced 1-, 3-, and 5-year tumor-free survival compared with group B patients (87.0%, 67.0%, and 62.6%, respectively, in group A; 82.1%, 50.0%, and 42.9% in group B, P = .002). In addition, the tumor recurrence rate in group B was significantly increased compared with group A (P < .01). Univariate and multivariate analyses indicated lack of postoperative anti-HBV therapy [hazard ratio (HR) = 0.882; 95% confidence interval (CI), 0.712–0.938; P = .042] to be a predictor of tumor recurrence. For intermediate-stage [Barcelona Clinic Liver Cancer (BCLC) stage B] HCC with a high HBV-DNA load, postoperative anti-HBV therapy after curative resection should be routine adjuvant therapy.

Inhibition of invasion by N-trans-feruloyloctopamine via AKT, p38MAPK and EMT related signals in hepatocellular carcinoma cells

N-trans-feruloyloctopamine (FO) isolated from Garlic skin was identified as the primary antioxidant constituents, however, the effect of which on HCC invasion is still unclear. Herein, the FO was synthesized and its antitumor activities were evaluated in HCC cell lines. Cellular functional analyses have revealed that the reformed FO owns strong abilities of inhibiting cell proliferation and invasion in HCC cells. Molecular data have further showed that FO could significantly decrease the phosphorylation levels of Akt and p38 MAPK. In addition, the expression of Slug was inhibited and the level of E-cadherin increased. Molecular docking analysis indicates that the H-bond and hydrophobic interactions were critical for FO and E-cadherin binding, but FO did not seem to act directly on phosphorylated Akt and p38 MAPK. We have thus concluded that reformed FO inhibits cell invasion might be directly through EMT related signals (E-cadherin) and indirectly through PI3K/Akt, p38 MAPK signaling pathways. FO might be a promising drug in HCC treatment and prognosis.