Effect of Helicobacter Pylori on Plasma Metabolic Phenotype in Patients With Gastric Cancer.

BACKGROUND: Although Helicobacter pylori (Hp) as high risk factor for gastric cancer have been investigated from human trial, present data is inadequate to explain the effect of Hp on the changes of metabolic phenotype of gastric cancer in different stages. PURPOSE: Herein, plasma of human superficial gastritis (Hp negative and positive), early gastric cancer and advanced gastric cancer analyzed by UPLC-HDMS metabolomics can not only reveal metabolic phenotype changes in patients with gastric cancer of different degrees (30 Hp negative, 30 Hp positive, 20 early gastric cancer patients, and 10 advanced gastric cancer patients), but also auxiliarily diagnose gastric cancer. RESULTS: Combined with multivariate statistical analysis, the results represented biomarkers different from Hp negative, Hp positive, and the alterations of metabolic phenotype of gastric cancer patients. Forty-three metabolites are involved in amino acid metabolism, and lipid and fatty acid metabolism pathways in the process of cancer occurrence, especially 2 biomarkers glycerophosphocholine and neopterin, were screened in this study. Neopterin was consistently increased with gastric cancer progression and glycerophosphocholine tended to consistently decrease from Hp negative to advanced gastric cancer. CONCLUSION: This method could be used for the development of rapid targeted methods for biomarker identification and a potential diagnosis of gastric cancer.

Impact of mechanical simulator practice on clinical ERCP performance by novice surgical trainees: a randomized controlled trial.

BACKGROUND: Lack of forward-viewing endoscopy experience impairs training in endoscopic retrograde cholangiopancreatography (ERCP). We evaluated the effect of ERCP mechanical simulator (EMS) practice on ERCP performance by surgical trainees. PATIENTS AND METHODS: 12 surgical trainees without endoscopy experience were randomly allocated to non-EMS (n = 6) programs or to EMS (n = 6) programs with coaching and 20 hours of supervised EMS practice. All trainees then received supervised hands-on clinical ERCP training. Trainers provided verbal instructions and hands-on assistance, and took over if cannulation was not achieved by 20 minutes. Blinded trainers rated clinical performance. RESULTS: Each group performed 150 clinical ERCPs. Biliary cannulation success was significantly higher in the EMS vs. the non-EMS group (P = 0.006), with shorter mean times (in minutes) for intubation, cannulation, and completion (all P < 0.001). EMS trainees showed a significantly better mean performance score (P = 0.006). In multivariate analysis, after adjusting for case sequence, CBD stone, complexity, and EMS training, the effect of EMS practice on odds for successful cannulation remained highly significant (odds ratio [OR] 2.10 [95 %CI 1.46 - 3.01]). At 6 months EMS trainees still had better cannulation success vs. non-EMS controls (P = 0.045); no difference was observed after 1 year. CONCLUSIONS: EMS practice shortens the ERCP early learning curve of inexperienced surgical trainees, improves clinical success in selective biliary cannulation, and may reduce complications.

Eukaryotic translation initiation factor 2α kinase 2 in pancreatic cancer: An approach towards managing clinical prognosis and molecular immunological characterization.

Most patients with pancreatic cancer are already in the late stages of the disease when they are diagnosed, and pancreatic cancer is a deadly disease with a poor prognosis. With the advancement of research, immunotherapy has become a new focus in the treatment of tumors. To the best of our knowledge, there is currently no reliable diagnostic or prognostic marker for pancreatic cancer; therefore, the present study investigated the potential of eukaryotic translation initiation factor 2α kinase 2 (EIF2AK2) as a predictive and diagnostic marker for pancreatic cancer. Immunohistochemical staining of clinical samples independently verified that EIF2AK2 expression was significantly higher in clinically operated pancreatic cancer tissues than in adjacent pancreatic tissues., and EIF2AK2 expression and differentially expressed genes (DEGs) were identified using downloadable RNA sequencing data from The Cancer Genome Atlas and Genomic Tumor Expression Atlas. In addition, Gene Ontology/Kyoto Encyclopedia of Genes and Genomes analyses and immune cell infiltration were used for functional enrichment analysis of EIF2AK2-associated DEGs. The clinical importance of EIF2AK2 was also determined using Kaplan-Meier survival, Cox regression and time-dependent survival receiver operating characteristic curve analyses, and a predictive nomogram model was generated. Finally, the functional role of EIF2AK2 was assessed in PANC-1 cells using a short hairpin RNA-EIF2AK2 knockdown approach, including CCK-8, wound healing assay, cell cycle and apoptosis assays. The findings suggested that EIF2AK2 may have potential as a diagnostic and prognostic biomarker for patients with pancreatic cancer. Furthermore, EIF2AK2 may provide a new therapeutic target for patients with pancreatic cancer.

Establishment and characterization of a new Chinese hepatocellular carcinoma cell line, Hep-X1.

Hepatocellular carcinoma (HCC) is a highly aggressive and heterogeneous disease. Cell lines are commonly employed as in vitro models for cell type studies. However, the success rate of HCC primary culture establishment is low. In this study, we successfully established a liver cancer cell line, Hep-X1. Primary culture and passage of surgically removed tissues were used to establish hepatoma cell lines. Morphological examination, short tandem repeat (STR) analysis, immunohistochemical staining, doubling time, karyotype analysis, plate tumor formation experiments, organoid culture, and in vivo tumor formation investigations in animals were used to identify the cell lines. A novel liver cancer cell line, Hep-X1, was established based on morphology, immunophenotype, cytogenetics, and STR analysis. The novel cell line can be a valuable model for studying primary liver cancer.

Safety of high-carbohydrate fluid diet 2 h versus overnight fasting before non-emergency endoscopic retrograde cholangiopancreatography: A single-blind, multicenter, randomized controlled trial.

BACKGROUND: Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients' recovery. METHODS: This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group (n = 665) and fasting group (n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. RESULTS: The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t = 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26-0.71, P <0.001) and 0.76 (95% CI: 0.57-0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05-0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39-0.95, P = 0.028) in the multivariable models. CONCLUSION: Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery. TRAIL REGISTRATION: ClinicalTrials.gov, No. NCT03075280.

Periampullary diverticulum may be an important factor for the occurrence and recurrence of bile duct stones.

BACKGROUND: The aim of this study was to examine the relation between periampullary diverticula (PAD) and biliary tract stones. METHODS: A total of 732 cases of patients with PAD identified from among 6,221 patients who underwent endoscopic retrograde cholangiopancreatography were compared to 750 controls (without PAD) in terms of biliary stone formation, incidence of sphincter of Oddi dysfunction (SOD), and choledocholithiasis. The biliary tract diseases were diagnosed based on medical history, clinical symptoms and signs, and imaging findings using ultrasonography, computed tomography, or magnetic resonance cholangiopancreatography. RESULTS: The PAD group contained a significantly larger number of patients with biliary stones including stones in the primary common bile duct, SOD with bile duct stones (p < 0.05), and choledocholithiasis after cholecystectomy (p < 0.01). CONCLUSIONS: There is a close correlation between PAD and the formation of biliary tract stones. A particularly close correlation was found between PAD and choledocholithiasis after cholecystectomy. PAD may be an important risk factor for the occurrence or recurrence of biliary tract stones.

Establishment of gastric cancer organoid and its application in individualized therapy.

The application of cancer organoids is of great value in individualized therapy as an embodiment of the tumor of a patient, a gastric cancer organoid model was established and its application in individualized drug screening was explored. The primary tumor tissues of 3 patients with gastric cancer who underwent primary surgery at the Fourth Department of General Surgery of the First Hospital of Lanzhou University (Lanzhou, China) between July and August 2021 were selected and digested with mixed enzymes to prepare cell suspensions. Of these, two were cultured by mixing with Matrigel, while the cells from the third patient were placed in a 24-well ultra-low adhesion plate for suspension organoid culture. After intensive organoid growth, they were digested, passaged, cryopreserved and thawed for further analyses. The formation of gastric cancer organoids was observed under an inverted microscope. One case was selected, and organoids were compared with the original tumor tissue via H&E and immunohistochemical staining to evaluate the consistency of the two. Finally, paclitaxel, oxaliplatin and fluorouracil were administered to the organoids to verify the value of screening individualized drugs. It was indicated that the passage and cryopreservation of gastric cancer organoids were successfully established in all three cases. The H&E and immunohistochemical staining results suggested that the structure and protein expression of the organoids were highly similar to those of the source tumor tissue. The use of established gastric cancer organoids for individualized chemotherapy drug screening is of high clinical value. Gastric cancer organoids with high similarity to the original tissue may be successfully constructed by the suspension growth culture method. The established organoids may serve as an effective model for individualized drug screening.

Choledocholithiasis characteristics with periampullary diverticulum and endoscopic retrograde cholangiopancreatography procedures: Comparison between two centers from Lanzhou and Kyoto.

BACKGROUND: Most of study regarding periampullary diverticulum (PAD) impact on endoscopic retrograde cholangiopancreatography (ERCP) therapy for choledocholithiasis based on data from one endoscopy center and lacked to compare the clinical characteristic of choledocholithiasis with PAD from different geographical patients. AIM: To compare the choledocholithiasis clinical characteristics between two regional endoscopy centers and analyze impacts of clinical characteristics on ERCP methods for choledocholithiasis patients with PAD. METHODS: Patients seen in two endoscopy centers (The First Hospital of Lanzhou University, Lanzhou, Gansu Province, China, and Kyoto Second Red Cross Hospital, Kyoto, Japan) underwent ERCP treatment for the first time between January 2012 and December 2017. The characteristics of choledocholithiasis with PAD were compared between the two centers, and their ERCP procedures and therapeutic outcomes were analyzed. RESULTS: A total of 829 out of 3608 patients in the Lanzhou center and 241 out of 1198 in the Kyoto center had choledocholithiasis with PAD. Lots of clinical characteristics were significantly different between the two centers. The common bile duct (CBD) diameter was wider, choledocholithiasis size was lager and multiple CBD stones were more in the Lanzhou center patients than those in the Kyoto center patients (14.8 ± 5.2 mm vs 11.6 ± 4.2 mm, 12.2 ± 6.5 mm vs 8.2 ± 5.3 mm, 45.3% vs 20.3%, P < 0.001 for all). In addition, concomitant diseases, such as acute cholangitis, gallbladder stones, obstructive jaundice, cholecystectomy, and acute pancreatitis, were significantly different between the two centers (P = 0.03 to < 0.001). In the Lanzhou center, CBD diameter and choledocholithiasis size were lower, and multiple CBD stones and acute cholangitis were less in non-PAD patients than those in PAD patients (13.4 ± 5.1 mm vs 14.8 ± 5.2 mm, 10.3 ± 5.4 mm vs 12.2 ± 6.5, 39% vs 45.3%, 13.9% vs 18.5%, P = 0.002 to < 0.001). But all these characteristics were not significantly different in the Kyoto center. The proportions of endoscopic sphincterotomy (EST), endoscopic balloon dilatation (EPBD), and EST+EPBD were 50.5%, 1.7%, and 42.5% in the Lanzhou center and 90.0%, 0.0%, and 0.4% in the Kyoto center, respectively. However, the overall post-ERCP complication rate was not significantly different between the two centers (8.9% in the Lanzhou and 5.8% in the Kyoto. P = 0.12). In the Lanzhou center, the difficulty rate in removing CBD stones in PAD was higher than in non-PAD group (35.3% vs 26.0%, P < 0.001). But the rate was no significant difference between the two groups in Kyoto center. The residual rates of choledocholithiasis were not significantly different between the two groups in both centers. Post-ERCP complications occurred in 8.9% of the PAD patients and 8.1% of the non-PAD patients in the Lanzhou Center, and it occurred in 5.8% in PAD patients and 10.0% in non-PAD patients in the Kyoto center, all P > 0.05. CONCLUSION: Many clinical characteristics of choledocholithiasis patients with PAD were significantly different between the Lanzhou and Kyoto centers. The patients had larger and multiple stones, wider CBD diameter, and more possibility of acute cholangitis and obstructive jaundice in the Lanzhou center than those in the Kyoto center. The ERCP procedures to manage native duodenal papilla were different depending on the different clinical characteristics while the overall post-ERCP complications were not significantly different between the two centers. The stone residual rate and post-ERCP complications were not significantly different between choledocholithiasis patients with PAD and without PAD in each center.

A novel machine learning model and a public online prediction platform for prediction of post-ERCP-cholecystitis (PEC).

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is an established treatment for common bile duct (CBD) stones. Post- ERCP cholecystitis (PEC) is a known complication of such procedure and there are no effective models and clinical applicable tools for PEC prediction. Methods: A random forest (RF) machine learning model was developed to predict PEC. Eligible patients at The First Hospital of Lanzhou University in China with common bile duct (CBD) stones and gallbladders in-situ were enrolled from 2010 to 2019. Logistic regression analysis was used to compare the predictive discrimination and accuracy values based on receiver operation characteristics (ROC) curve and decision and clinical impact curve. The RF model was further validated by another 117 patients. This study was registered with ClinicalTrials.gov, NCT04234126. Findings: A total of 1117 patients were enrolled (90 PEC, 8.06%) to build the predictive model for PEC. The RF method identified white blood cell (WBC) count, endoscopic papillary balloon dilatation (EPBD), increase in WBC, residual CBD stones after ERCP, serum amylase levels, and mechanical lithotripsy as the top six predictive factors and has a sensitivity of 0.822, specificity of 0.853 and accuracy of 0.855, with the area under curve (AUC) value of 0.890. A separate logistic regression prediction model was built with sensitivity, specificity, and AUC of 0.811, 0.791, and 0.864, respectively. An additional 117 patients (11 PEC, 9.40%) were used to validate the RF model, with an AUC of 0.889 compared to an AUC of 0.884 with the logistic regression model. Interpretation: The results suggest that the proposed RF model based on the top six PEC risk factors could be a promising tool to predict the occurrence of PEC.

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.

Ectopic opening of the common bile duct into the duodenal bulb with recurrent choledocholithiasis: A case report.

BACKGROUND: Ectopic opening of the common bile duct is a condition with low incidence. Patients with an ectopic common bile duct opening have a high incidence of common bile duct stones and acute cholangitis. Patients with atypical symptoms and imaging findings are easily misdiagnosed; moreover, it is difficult to retrieve stones by endoscopic retrograde cholangiopancreatography, and common bile duct stones are prone to postsurgical recurrence. CASE SUMMARY: A 45-year-old male patient presented with "intermittent upper abdominal pain and elevated liver enzymes for 1 wk". Transabdominal ultrasound indicated dilation of the common bile duct and the presence of stones. Magnetic resonance imaging showed that the common bile duct was dilated with stones and that its opening was ectopic. Endoscopic retrograde cholangiopancreatography revealed an abnormal opening of the common bile duct into the duodenal bulb and the presence of common bile duct stones. Laparoscopic extrahepatic choledochectomy and hepatoenteric anastomosis were performed. After surgery, the patient recovered well and was discharged. The patient has been followed up for 2 years since the operation. He has not experienced stone recurrence, and his liver function and quality of life are good. CONCLUSION: Improved understanding of ectopic opening of the common bile duct is needed for clinicians to provide patients with appropriate treatment.

MiR-142-3p targeting NUCKS1 inhibits proliferation and invasion of pancreatic cancer cells.

Objective: To investigate the effects of microRNA-142-3p (miR-142-3p) on the biological characteristics of pancreatic cancer cells and its mechanism.Methods: The expression of miR-142-3p and nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1) in pancreatic tissues and four cancer cell lines (Panc-1, BxPC-3, AsPC-1, MIA-PaCa2) were detected by Quantitative PCR (qPCR) or Western blot. The cell viability of pancreatic cancer cells was examined by MTT assay. The apoptosis of pancreatic cancer cells was measured by flow cytometry. Transwell assay was utilized to test the migration and invasion of pancreatic cancer cells. Bioinformatics analysis for miR-142-3p was conducted and the dual luciferase reporter gene assay was utilized to further validate the predicted target relationship. The protein levels of PI3K, p-AKT and T-AKT were analyzed by Western blot.Results: The expression of miR-142-3p was down-regulated, while the expression of NUCKS1 was significantly up-regulated in pancreatic tissues and four cancer cell lines. The expression of miR-142-3p in pancreatic tissues was inversely correlated with NUCKS1 expression. Overexpression of miR-142-3p inhibited the cell viability, cell migration, and invasion, while promoted cell apoptosis of AsPC-1 and MIA-PaCa2 cells. MiR-142-3p targeted NUCKS1 and negatively regulated NUCKS1. Overexpression of miR-142-3p decreased PI3K and p-AKT expression. Up-regulation of NUCKS1 partially reversed the effects of the overexpression of miR-142-3p on the cell viability, cell apoptosis, migration and invasion, as well as PI3K and p-AKT expression in AsPC-1 and MIA-PaCa2 cells.Conclusion: MiR-142-3p regulated the biological characteristics of pancreatic cancer cells by directly targeting NUCKS1.

The efficacy and adverse effects of PARP inhibitor combined with chemotherapy compared with chemotherapy alone in the treatment of cancer patient: A protocol for systematic review.

BACKGROUND: There search of PARP inhibitors has made great breakthroughs and progress. Become a new type of medicine for cancer treatment,bringing hope to more advanced cancer patients.The purpose of this systematic review is to evaluate the clinical efficacy and adverse effects of PARP inhibitorscombined with chemotherapy and chemotherapy alone in the treatment of cancer patients. METHODS: We searched the following 4 databases, including: PubMed, EMBASE, Web of Science, and Cochrane Library. The search will also be conducted at the clinical trial centers: ClinicalTrials.gov, ISRCTN Registry, WHO International Clinical Trials Registration Platform. The search date is as of September 22, 2020. There is no language restriction during this search, and the latest documents are kept updated through settings. The subject search terms were identified as "PARP Inhibitor", "Neoplasms" and "Dug therapy". The Phase 2 and Phase 3 clinical trials comparing PARP inhibitor combined with chemotherapy and chemotherapy alone were included. The results include overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and adverse events. Two researchers separately completed the article inclusion, data extraction and quality evaluation of this study. The assessment of the risk of bias and data will be conducted using Review Manager. ETHICS AND DISSEMINATION: All articles are published and do not require the approval of the ethics committee and the signed informed consent form. The results of this systematic review will be published through peer-reviewed publications. REGISTERED: Registered on INPLASY and the registration number is INPLASY202090087.

Percutaneous transhepatic biliary drainage may be the preferred preoperative drainage method in hilar cholangiocarcinoma.

Background and study aims Preoperative biliary drainage of hilar cholangiocarcinoma (HC) is controversial. The goal of this study was to compare the clinical outcome and associated complications for types II, III, and IV HC managed by percutaneous transhepatic biliary drainage (PTBD) and endoscopic retrograde cholangiopancreatography (ERCP). Patients and methods Between January 2011 and June 2017, a total of 180 patients with II, III, and IV HC were enrolled in this retrospective cohort study. According to the drainage method, patients were divided into two groups: PTBD (n = 81) and ERCP (n = 99). This study was registered with ClinicalTrials.gov, NCT03104582, and was completed. Results Compared with the PTBD group, the ERCP group had a higher incidence of post-procedural cholangitis (37 [37.37 %] vs. 18 [22.22 %], P  = 0.028) and pancreatitis (17 [17.17 %] vs. 2 [2.47 %], P  = 0.001); required more salvaged biliary drainage (18 [18.18 %] vs. 5 [6.17 %], P  = 0.029), and incurred a higher cost ( P  < 0.05). Patients with type III and IV HC in the ERCP group had more cholangitis than those in the PTBD group (26 [36.62 %] vs. 11 [18.03 %], P  = 0.018). The rate of cholangitis in patients who received endoscopic bilateral biliary stents insertion was higher than patients with unilateral stenting (23 [50.00 %] vs. 9 [26.47 %], P  = 0.034), and underwent PTBD internal-external drainage had a higher incidence of cholangitis than those with only external drainage (11 [34.36 %] vs. 7 [14.29 %], P  = 0.034). No significant difference in the rate of cholangitis was observed between the endoscopic unilateral stenting group and the endoscopic nasobiliary drainage group (9 [26.47 %] vs. 5 [26.32 %], P  = 0.990). Conclusion Compared to ERCP, PTBD reduced the rate of cholangitis, pancreatitis, salvage biliary drainage, and decreased hospitalization costs in patients with types II, III, and IV HC. Risk of cholangitis for patients with types III and IV was significantly lower in the PTBD group.

Clinical significance of different periampullary diverticulum classifications for endoscopic retrograde cholangiopancreatography cannulation.

BACKGROUND: Different types of periampullary diverticulum (PAD) may differentially affect the success of endoscopic retrograde cholangiopancreatography (ERCP) cannulation, but the clinical significance of the two current PAD classifications for cannulation is limited. AIM: To verify the clinical value of our newly proposed PAD classification. METHODS: A new PAD classification (Li-Tanaka classification) was proposed at our center. All PAD patients with native papillae who underwent ERCP from January 2012 to December 2017 were classified according to three classification systems, and the effects of various types of PAD on ERCP cannulation were compared. RESULTS: A total of 3564 patients with native papillae were enrolled, including 967 (27.13%) PAD patients and 2597 (72.87%) non-PAD patients. In the Li-Tanaka classification, type I PAD patients exhibited the highest difficult cannulation rate (23.1%, P = 0.01), and type II and IV patients had the highest cannulation success rates (99.4% in type II and 99.3% in type IV, P < 0.001). In a multivariable-adjusted logistic model, the overall successful cannulation rate in PAD patients was higher than that in non-PAD patients [odds ratio (OR) = 1.87, 95% confidence interval (CI): 1.04-3037, P = 0.037]. In addition, compared to the non-PAD group, the difficulty of cannulation in the type I PAD group according to the Li-Tanaka classification was greater (OR = 2.04, 95%CI: 1.13-3.68, P = 0.004), and the successful cannulation rate was lower (OR = 0.27, 95%CI: 0.11-0.66, P < 0.001), while it was higher in the type II PAD group (OR = 4.44, 95%CI: 1.61-12.29, P < 0.01). CONCLUSION: Among the three PAD classifications, the Li-Tanaka classification has an obvious clinical advantage for ERCP cannulation, and it is helpful for evaluating potentially difficult and successful cannulation cases among different types of PAD patients.

Plasma microRNAs as potential new biomarkers for early detection of early gastric cancer.

BACKGROUND: Early gastric cancer (EGC), compared with advanced gastric cancer (AGC), has a higher 5-year survival rate. However, due to the lack of typical symptoms and the difficulty in diagnosing EGC, no effective biomarkers exist for the detection of EGC, and gastroscopy is the only detection method. AIM: To provide new biomarkers with high specificity and sensitivity through analyzed the differentially expressed microRNAs (miRNAs) in EGC and AGC and compared them with those in benign gastritis (BG). METHODS: We examined the differentially expressed miRNAs in the plasma of 30 patients with EGC, AGC, and BG by miRNA chip analysis. Then, we analyzed and selected the significantly different miRNAs using bioinformatics. Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) confirmed the relative transcription level of these miRNAs in another 122 patients, including patients with EGC, AGC, Helicobacter pylori (H. pylori)-negative gastritis (Control-1), and H. pylori-positive atrophic gastritis (Control-2). To establish a diagnostic model for the detection of plasma miRNA in EGC, we chose miRNAs that can be used to determine EGC and AGC from Control-1 and Control-2 and miRNAs in EGC from all other groups. RESULTS: Among the expression profiles of the miRNA chips in the three groups in the discovery set, of 117 aberrantly expressed miRNAs, 30 confirmed target prediction, whereas 14 were included as potential miRNAs. The RT-qPCR results showed that 14 potential miRNAs expression profiles in the two groups exhibited no differences in terms of H. pylori-negative gastritis (Control-1) and H. pylori-positive atrophic gastritis (Control-2). Hence, these two groups were incorporated into the Control group. A combination of four types of miRNAs, miR-7641, miR-425-5p, miR-1180-3p and miR-122-5p, were used to effectively distinguish the Cancer group (EGC + AGC) from the Control group [area under the curve (AUC) = 0.799, 95% confidence interval (CI): 0.691-0.908, P < 0.001]. Additionally, miR-425-5p, miR-24-3p, miR-1180-3p and miR-122-5p were utilized to distinguish EGC from the Control group (AUC = 0.829, 95%CI: 0.657-1.000, P = 0.001). Moreover, the miR-24-3p expression level in EGC was lower than that in the AGC (AUC = 0.782, 95%CI: 0.571-0.993, P = 0.029), and the miR-4632-5p expression level in EGC was significantly higher than that in AGC (AUC = 0.791, 95%CI: 0.574-1.000, P = 0.024). CONCLUSION: The differentially expressed circulatory plasma miR-425-5p, miR-1180-3p, miR-122-5p, miR-24-3p and miR-4632-5p can be regarded as a new potential biomarker panel for the diagnosis of EGC. The prediction and early diagnosis of EGC can be considerably facilitated by combining gastroscopy with the use of these miRNA biomarkers, thereby optimizing the strategy for effective detection of EGC. Nevertheless, larger-scale human experiments are still required to confirm our findings.

Optimal dilation time for combined small endoscopic sphincterotomy and balloon dilation for common bile duct stones: a multicentre, single-blinded, randomised controlled trial.

BACKGROUND: Endoscopic sphincterotomy is the established treatment for common bile duct stones. Balloon dilation offers an alternative. Prolonged dilation (300 s) with a 10 mm diameter balloon decreases the occurrence of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). We aimed to determine the optimal duration of dilation for combined endoscopic sphincterotomy and balloon dilation for the removal of common bile duct stones. METHODS: We did a multicentre, single-blinded, randomised controlled trial at 15 tertiary surgical centres in China. Eligible patients (≥18 years) with native papilla and common bile duct stones (≤1·5 cm in size and <2 cm in diameter) undergoing ERCP were randomly assigned (1:1:1:1:1) to receive balloon dilation for 0, 30, 60, 180, or 300 s after deep bile duct cannulation. Randomisation was done by an independent statistician using a computer-generated randomisation list with a block size of ten, stratified by centre. Patients and outcome assessors, but not endoscopists and investigators, were masked to treatment allocation. Balloon dilation was done with controlled radial expansion balloons according to common bile duct stone size. Stones were removed using stone retrieval balloons or baskets. The primary endpoint was overall frequency of post-ERCP pancreatitis. The primary efficacy analysis and safety analyses were done in the modified intention-to-treat population, which included all randomly assigned patients with successful cannulation, but excluded those who withdrew consent after randomisation. This study was registered with ClinicalTrials.gov, number NCT02510495, and is complete. FINDINGS: Between July 29, 2015, and Dec 1, 2017, 3721 consecutive patients with common bile duct stones were recruited, 1718 of whom were excluded. The remaining 2003 patients underwent a small (3-5 mm) endoscopic sphincterotomy. 83 patients withdrew consent after the ERCP procedure, thus 1920 patients were included in the modified intention-to-treat analysis (0 s [n=371], 30 s [n=384], 60 s [n=388], 180 s [n=390], and 300 s [n=387]). Overall, post-ERCP pancreatitis occurred in 199 (10%) of 1920 patients (44 [12%] patients in the 0 s group, 28 [7%] in the 30 s group, 32 [8%] in the 60 s group, 36 [9%] in the 180 s group, and 59 [15%] in the 300 s group). Prolonged dilation (300 s) significantly increased the occurrence of post-ERCP pancreatitis compared with shorter balloon dilation (p=0·002). The frequency of post-ERCP pancreatitis was significantly lower in the 30, 60, and 180 s groups than in the 300 s group (relative risk [RR] 0·48, 95% CI 0·31-0·73; p=0·0005 vs the 30 s group; 0·54, 0·36-0·81; p=0·003 vs the 60 s group; 0·61, 0·41-0·89; p=0·01 vs the 180 s group). The frequency of post-ERCP pancreatitis was significantly higher in the 0 s group than the 30 s group (RR 1·62, 1·04-2·56; p=0·03). No difference in stone extraction (all ≥90%) was observed between groups. Following ERCP, 90 (5%) of 1920 patients had acute cholangitis, 14 (<1%) had acute cholecystitis, and five (<1%) had gastrointestinal bleeding, with no significant differences between groups. One (<1%) patient had Stapfer II perforation, which resolved spontaneously with conservative treatment. INTERPRETATION: A balloon dilation time of 30 s for combined endoscopic sphincterotomy and balloon dilation reduced the frequency of post-ERCP pancreatitis and was determined to be the optimum dilation time for the removal of common bile duct stones. FUNDING: National Natural Science Foundation of China, Gansu Competitive Foundation Projects for Technology Development and Innovation.

Garlic-derived allyl sulfides in cancer therapy.

Garlic (Allium sativam L.) is widely used in traditional herbal remedies and alternative medicine. The potential health benefits of garlic are largely attributed to its metabolic byproducts. Extensive in vivo and in vitro studies has demonstrated that the garlic derivatives possess anti-cancer effects, but the underlying mechanisms are not completely understood. In this mini-review, we aim to summarize the reported biological effects of garlic products as anti-tumor agents, and present the possible molecular mechanisms responsible for the anti-carcinogenesis effects of garlic and its derivatives.

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.