Effects of Clip Anchoring on Preventing Migration of Fully Covered Self-Expandable Metal Stent in Patients Undergoing Endoscopic Retrograde Cholangiopancreatography: A Multicenter, Randomized Controlled Study.

INTRODUCTION: Fully covered self-expandable metal stents (FCSEMSs) are commonly placed in patients with biliary stricture during endoscopic retrograde cholangiopancreatography (ERCP). However, up to 40% of migration has been reported, resulting in treatment failure or the requirement for further intervention. Here, we aimed to investigate the effects of metal clip anchoring on preventing the migration of FCSEMS. METHODS: Consecutive patients requiring placement of FCSEMS were included in this multicenter randomized trial. The enrolled patients were randomly assigned in a 1:1 ratio to receive clip anchoring (clip group) or not (control group). The primary outcome was the migration rate at 6 months after stent insertion. The secondary outcomes were the rates of proximal and distal migration and stent-related adverse events. The analysis followed the intention-to-treat principle. RESULTS: From February 2020 to November 2022, 180 patients with biliary stricture were enrolled, with 90 in each group. The baseline characteristics were comparable between the 2 groups. The overall rate of stent migration at 6 months was significantly lower in the clip group compared with the control group (16.7% vs 30.0%, P = 0.030). The proximal and distal migration rates were similar in the 2 groups (2.2% vs 5.6%, P = 0.205; 14.4% vs 22.2%, P = 0.070). Notably, none of the patients (0/8) who received 2 or more clips experienced stent migration. There were no significant differences in stent-related adverse events between the 2 groups. DISCUSSION: Our data suggest that clip-assisted anchoring is an effective and safe method for preventing migration of FCSEMS without increasing the adverse events.

Metabolome and Transcriptome Unveil the Correlated Metabolites and Transcripts with 2-acetyl-1-pyrroline in Fragrant Rice.

Fragrance is a valuable trait in rice varieties, with its aroma significantly influencing consumer preference. In this study, we conducted comprehensive metabolome and transcriptome analyses to elucidate the genetic and biochemical basis of fragrance in the Shangsixiangnuo (SSXN) variety, a fragrant indica rice cultivated in Guangxi, China. Through sensory evaluation and genetic analysis, we confirmed SSXN as strongly fragrant, with an 806 bp deletion in the BADH2 gene associated with fragrance production. In the metabolome analysis, a total of 238, 233, 105 and 60 metabolic compounds exhibited significant changes at the seedling (S), reproductive (R), filling (F), and maturation (M) stages, respectively. We identified four compounds that exhibited significant changes in SSXN across all four development stages. Our analyses revealed a significant upregulation of 2-acetyl-1-pyrroline (2AP), the well-studied aromatic compound, in SSXN compared to the non-fragrant variety. Additionally, correlation analysis identified several metabolites strongly associated with 2AP, including ethanone, 1-(1H-pyrrol-2-yl)-, 1H-pyrrole, and pyrrole. Furthermore, Weighted Gene Co-expression Network Analysis (WGCNA) analysis highlighted the magenta and yellow modules as particularly enriched in aroma-related metabolites, providing insights into the complex aromatic compounds underlying the fragrance of rice. In the transcriptome analysis, a total of 5582, 5506, 4965, and 4599 differential expressed genes (DEGs) were identified across the four developmental stages, with a notable enrichment of the common pathway amino sugar and nucleotide sugar metabolism in all stages. In our correlation analysis between metabolome and transcriptome data, the top three connected metabolites, phenol-, 3-amino-, and 2AP, along with ethanone, 1-(1H-pyrrol-2-yl)-, exhibited strong associations with transcripts, highlighting their potential roles in fragrance biosynthesis. Additionally, the downregulated expression of the P4H4 gene, encoding a procollagen-proline dioxygenase that specifically targets proline, in SSXN suggests its involvement in proline metabolism and potentially in aroma formation pathways. Overall, our study provides comprehensive insights into the genetic and biochemical mechanisms underlying fragrance production in rice, laying the foundation for further research aimed at enhancing fragrance quality in rice breeding programs.

Transcutaneous Auricular Vagal Nerve Stimulation Is Effective for the Treatment of Functional Dyspepsia: A Multicenter, Randomized Controlled Study.

INTRODUCTION: Vagal nerve stimulation (VNS) can be used to modulate gastrointestinal motility, inflammation, and nociception. However, it remains unclear whether VNS is effective in adult patients with functional dyspepsia (FD). We investigated the effectiveness of transcutaneous auricular VNS (taVNS) in patients with FD. METHODS: Consecutive patients with FD meeting Rome IV criteria with modified FD Symptom Diary score ≥10 were enrolled. Patients were randomly allocated to 10-Hz taVNS (V10 group), 25-Hz taVNS (V25 group), or sham group, with 30 minutes of treatment twice a day for 4 weeks. The primary outcome was the response rate at week 4, defined as the proportion of patients whose modified FD Symptom Diary score was reduced ≥5 when compared with the baseline. Secondary outcomes included adequate relief rate and adverse events. RESULTS: A total of 300 patients were randomized to V10 (n = 101), V25 (n = 99), and sham groups (n = 100). After 4 weeks of treatment, V10 and V25 groups had a higher response rate (81.2% vs 75.9% vs 47%, both P < 0.001) and adequate relief rate (85.1% vs 80.8% vs 67%, both P < 0.05) compared with the sham group. There was no significant difference between V10 and V25 in response rate and adequate relief rate (both P > 0.05). The efficacy of taVNS (both 10 and 25 Hz) lasted at week 8 and week 12 during follow-up period. Adverse events were all mild and comparable among the 3 groups (1%-3%). DISCUSSION: Our study firstly showed that 4-week taVNS (both 10 and 25 Hz) was effective and safe for the treatment of adult FD ( clinicaltrials.gov number: NCT04668534).

Endoscopic Papillary Large Balloon Dilation Reduces Further Recurrence in Patients With Recurrent Common Bile Duct Stones: A Randomized Controlled Trial.

INTRODUCTION: Up to 60% of patients with common bile duct stone (CBDS) recurrence suffer from further recurrence after endoscopic retrograde cholangiopancreatography (ERCP). There are no effective methods to prevent recurrence in most patients. In this study, we aimed to assess the short-term and long-term efficacies of endoscopic papillary large balloon dilation (EPLBD) for the management of recurrent CBDS in a randomized controlled trial. METHODS: Consecutive patients with recurrent CBDS were eligible and randomly assigned in a 1:1 ratio to the EPLBD group or the control group. The primary outcome was the CBDS recurrence rate within 2 years after ERCP. The analysis followed the intention-to-treat principle. RESULTS: From 2014 to 2021, 180 patients with recurrent CBDS were included, with 90 in each group. All patients underwent complete CBDS clearance by 1 or several sessions of ERCP. The rate of complete clearance in 1 session was significantly higher with EPLBD treatment (95.6% vs 85.6%, P = 0.017). During the follow-up, the CBDS recurrence rate within 2 years was significantly lower in the EPLBD group than in the control group (21.1% [19/90] vs 36.7% [33/90], relative risk 0.58, 95% confidence interval 0.36-0.93, P = 0.021). At a median follow-up of approximately 56 months, CBDS recurrence was found in 34.4% of the patients (31/90) in the EPLBD group and 51.1% (46/90) in the control group (hazard ratio 0.57, 95% confidence interval 0.36-0.89, P = 0.012). Multiple recurrences (≥2) were also decreased in the EPLBD group (4.4% vs 18.9%, P = 0.020). DISCUSSION: During the long-term follow-up, nearly half of the patients with recurrent CBDS experienced stone recurrence after traditional ERCP. Our study was the first to show that EPLBD effectively reduced the recurrence of CBDS.

Difficult biliary cannulation in ERCP procedures with or without trainee involvement: a comparative study.

BACKGROUND: The 5-5-1 criteria (> 5 minutes - 5 cannulation attempts - 1 unintended pancreas duct cannulation) were proposed by the European Society of Gastrointestinal Endoscopy to define difficult biliary cannulation. However, the criteria may be inappropriate for trainee-involved procedures. We developed criteria for difficult cannulation in trainee-involved procedures. METHODS: Patients undergoing biliary cannulation with or without trainee involvement were eligible. Procedures that might be too easy (e. g. fistula) or too difficult (e. g. altered anatomy) were excluded. The primary outcome was difficult cannulation, defined as cannulation time, attempts, or inadvertent pancreatic duct (PD) cannulation exceeding the 75 % percentile of each variable. Propensity score matching (PSM) analysis was used. RESULTS: After PSM, there were 1596 patients in each group. Trainee-involved procedures had longer median (interquartile range [IQR]) cannulation time (7.5 [2.2-15.3] vs. 2.0 [0.6-5.2] minutes), and more attempts (5 [2-10] vs. 2 [1-4]) and inadvertent PD cannulation (0 [0-2] vs. 0 [0-1]) vs. procedures without trainee involvement (all P < 0.001). The 15-10-2 criteria for difficult cannulation were proposed for trainee-involved cannulation and the 5-5-1 criteria were nearly confirmed for cannulation without trainee involvement. The proportions of difficult cannulation using these respective criteria were 35.5 % (95 % confidence interval [CI] 33.2 %-37.9 %) and 31.8 % (95 %CI 29.5 %-34.2 %), respectively (odds ratio 1.18 [95 %CI 1.02-1.37]). Incidences of post-ERCP pancreatitis following difficult cannulation were comparable (7.8 % [95 %CI 5.7 %-10.3 %] vs. 9.8 % [95 %CI 7.4 %-12.8 %], respectively). CONCLUSION: By using the 75 % percentiles as cutoffs, the proposed 15-10-2 criteria for difficult cannulation could be appropriate in trainee-involved procedures.

Water exchange-assisted versus carbon dioxide-insufflated single-balloon enteroscopy: a randomized controlled trial.

BACKGROUND: Single-balloon enteroscopy (SBE) is a valuable but difficult modality for the diagnosis and treatment of small-bowel disease. The water exchange method has the advantage of facilitating intubation during colonoscopy. Here, we evaluated the effects of water exchange on procedure-related variables related to SBE. METHODS: This randomized controlled trial was conducted in a tertiary-care referral center in China. Patients due for attempted total enteroscopy were randomly allocated to undergo water exchange-assisted (water exchange group) or carbon dioxide-insufflated enteroscopy (CO2 group). All patients were planned to undergo both anterograde and retrograde procedures. The primary outcome was the total enteroscopy rate. Secondary outcomes included the maximal insertion depth, positive findings, procedural time, and adverse events. RESULTS: In total, 110 patients were enrolled, with 55 in each group. Baseline characteristics between the two groups were comparable. Total enteroscopy was achieved in 58.2 % (32/55) of the water exchange group and 36.4 % (20/55) of the control group (P = 0.02). The mean (standard deviation) estimated intubation depth was 521.2 (101.4) cm in the water exchange group and 481.6 (95.2) cm in the CO2 group (P = 0.04). The insertion time was prolonged in the water exchange group compared with the CO2 group (178.9 [45.1] minutes vs. 154.2 [27.6] minutes; P < 0.001). Endoscopic findings and adverse events were comparable between the two groups. CONCLUSIONS: The water exchange method improved the total enteroscopy rate and increased the intubation depth during SBE. The use of water exchange did not increase the complications of enteroscopy.

Functional dyspepsia symptom diary is correlated with other questionnaires and associated with severity in patients with functional dyspepsia: a multicenter, prospective observational study.

BACKGROUND AND AIM: Functional dyspepsia symptom diary (FDSD) is a newly designed questionnaire of functional dyspepsia (FD). The relationships between FDSD and other FD-related questionnaires and patient-reported severity remain unclear. This study aims to investigate the correlations between FDSD and other questionnaires and to determine the relationships between FDSD and FD severity. METHODS: Consecutive outpatients with FD were prospectively enrolled in four tertiary hospitals. All patients were evaluated by six FD-related questionnaires, including FDSD, Dyspepsia Symptom Severity Index (DSSI), Gastrointestinal Symptom Rating Scale, Short-Form Nepean Dyspepsia Index, and Hamilton Depression and Anxiety Scale (HAMD and HAMA). The severity of FD was also graded as mild, moderate, and severe by patients themselves. Correlations between different scores were assessed by Spearman correlation coefficient (ρ), and risk factors for patient-reported severity were identified. RESULTS: For 512 enrolled FD patients, the overall median FDSD score was 19 (2-42). FDSD was well correlated with DSSI (ρ = 0.64) and fairly correlated with the other four scores (ρ = 0.32-0.55) (all P < 0.001). Mild, moderate, and severe FD were reported by 18.5%, 55.9%, and 25.6% of patients, respectively. There were seven factors associated with the severe FD, including education level, duration, and subtypes of FD, prior treatment, FDSD, HAMD, and HAMA scores (all P < 0.10). FDSD ≥ 20 (odds ratio [OR] 3.3, 95% confidence interval [CI]: 2.0-5.2, P < 0.001) and HAMD ≥ 13 (OR 2.9, 95% CI: 1.8-4.6, P < 0.001) were independently associated with patient-reported severe FD. CONCLUSIONS: This study firstly revealed that the newly developed FDSD correlated with other FD-related questionnaires. FDSD ≥ 20 and HAMD ≥ 13 were independently associated with severe FD reported by patients (clinicaltrials.gov number: NCT04953975).

Combination prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis in patients undergoing double-guidewire assisted biliary cannulation: A case-control study with propensity score matching.

BACKGROUND AND AIM: Rectal indomethacin and pancreatic duct stenting (PDS) are recommended for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). However, the effects of the combination of the two methods on preventing PEP are controversial. We hypothesized that some group of difficult patients might benefit from the combination of indomethacin plus PDS (IP) compared with indomethacin alone (IN). METHODS: Patients with native papilla who underwent endoscopic retrograde cholangiopancreatography in eight tertiary hospitals were screened. They were enrolled if the cannulation proved difficult and post-procedure indomethacin was administered. Propensity score matching (PSM) was used to balance the baseline characteristics between IP and IN groups. The primary outcome was PEP. RESULTS: Among 4456 patients with available cannulation-related data, 1889 (42.4%) patients had difficult cannulation and received indomethacin. After PSM, both IP and IN groups included 332 patients. PEP was comparable between the two groups (12.7% vs 10.2%, P = 0.329). By subgroup analysis, the PEP rate was found to be lower in the IP group than in the IN group (7.3% vs 18.2%, P = 0.026) in patients undergoing double-guidewire technique (DGT). The results of an additional analysis using PSM in DGT patients were consistent with the subgroup analysis results (7.8% vs 19.4%, P = 0.036). CONCLUSIONS: The current study indicated that the combined prevention of PEP with indomethacin plus PDS was useful in PEP prevention in patients undergoing DGT. Other groups of patients with difficult cannulation may not benefit from the combination strategy.

Relationship between papilla-related variables and post endoscopic retrograde cholangiopancreatography pancreatitis: A multicenter, prospective study.

BACKGROUND AND AIM: Papilla with hooknose or long protruding shape may increase the difficulty of cannulation during endoscopic retrograde cholangiopancreatography (ERCP). However, the relationship between papilla anatomy and complications of ERCP has not been fully understood. We aimed to investigate the effect of major duodenal papilla morphology on post-ERCP pancreatitis (PEP) and the procedure of cannulation. METHODS: Patients with native papilla who underwent ERCP were recruited to this multicenter study. Papilla-related variables were collected, including the length of long axis (L), short axis (S) and opening width (OW), transverse fold, periampullary diverticulum (PAD), papilla location, orientation, swelling, and presence of duodenal stenosis. Demographic data and the procedure of cannulation were also prospectively evaluated. The primary outcome was PEP incidence. Multivariate analysis was used to identify high risk factors for PEP. RESULTS: Six hundred and fifty-eight patients were enrolled. Overall PEP incidence was 4.7% (31/658). The papilla of patients complicated with PEP had higher long to short axis (L/S) ratio (odds ratio [OR] 3.84, 95% confidence interval [CI]: 1.37-10.74, P = 0.010), higher long axis to opening width (L/OW) ratio (OR 1.35, 95%CI: 1.06-1.71, P = 0.014), more transverse folds (OR 2.53, 95%CI: 1.02-6.26, P = 0.044), and less periampullary diverticulum (OR 0.21, 95%CI: 0.06-0.70, P = 0.011). Multivariate analysis revealed that the indication of common bile duct stones, normal bilirubin, inadvertent pancreatic duct cannulation > 1, L/S ratio ≥ 1.5, and absence of PAD were independent risk factors for PEP. CONCLUSION: Besides patient-related and procedure-related factors, papilla-related variables, such as L/S ratio and PAD, can be considered as a third type of factors associated with PEP (Clinicaltrials.gov number: NCT03550768).

Learning curve of double-guidewire technique by trainees during hands-on endoscopic retrograde cholangiopancreatography training.

BACKGROUND AND AIMS: Double-guidewire technique (DWT) has been successfully performed by experts in difficult biliary cannulation as an advanced technique. This study aimed to define the learning curve and safety of DWT by trainees during hands-on endoscopic retrograde cholangiopancreatography (ERCP) training. METHODS: Patients were eligible for inclusion in the study if the biliary cannulation was difficult and the pancreatic duct was inadvertently cannulated. DWT was performed by two trainees randomly under trainers' guidance. The primary outcome was the success rate of DWT biliary cannulation of trainees. Cumulative sum analysis was used to generate visual learning curves. RESULTS: A total of 60 patients with difficult cannulation were enrolled. The main indications for ERCP were common bile duct stones (65%) and biliary stricture (31.7%). The learning curve analysis showed that to achieve a 70% rate of successful DWT, 12 procedures were needed for trainee A and 15 for trainee B. Higher targeted success rate of DWT could be achieved if the number of DWT procedures increased. Compared with the early stage of learning DWT (case 1 to 15 for each trainee), trainees had significantly higher DWT success rate in the late stage (36.7% [11/30] vs 80% [24/30], P = 0.001). The final success rate of cannulation was 98.3% (59/60). The overall rate of post-ERCP pancreatitis and adverse events was 6.7% (4/60) and 8.3% (5/60), respectively. CONCLUSIONS: Double-guidewire technique was safely performed by two novel trainees during hands-on ERCP training. Fifteen procedures may be enough for trainees to achieve the competency of performing DWT. (Clinicaltrials.gov number: NCT03707613).

Rectal Indomethacin and Spraying of Duodenal Papilla With Epinephrine Increases Risk of Pancreatitis Following Endoscopic Retrograde Cholangiopancreatography.

BACKGROUND & AIMS: Rectal indomethacin and spraying of the duodenal papilla with epinephrine might reduce the incidence of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). We performed a randomized trial to compare the effects of the combination of indomethacin and epinephrine (IE) vs indomethacin plus saline (IS) in prophylaxis of post-ERCP pancreatitis (PEP). METHODS: We performed a double-blind trial at 10 centers in China, from February 2017 to October 2017, of 1158 patients with native papilla undergoing ERCP. The patients were assigned randomly to groups given IE (n = 576) or IS (n = 582). All patients received a single dose of rectal indomethacin within 30 minutes before ERCP; 20 mL of dilute epinephrine (IE group) or saline (IS group) then was sprayed on the duodenal papilla at the end of ERCP. The primary outcome was the incidence of overall PEP. Data were analyzed on an intention-to-treat principle. RESULTS: The study was terminated at the interim analysis for safety concerns and futility. The groups had similar baseline characteristics. PEP developed in 49 patients in the IE group (8.5%) and in 31 patients in the IS group (5.3%) (relative risk, 1.60, 95% CI, 1.03-2.47; P = .033). There were no significant differences between groups in proportions of patients with postsphincterotomy bleeding (2.1% in the IE group and 1.5% in the IS group) and biliary infection (1.2% in the IE group and 2.2% in the IS group). CONCLUSIONS: In a randomized trial, we found the combination of rectal indomethacin with papillary epinephrine spraying increased the risk of PEP compared with indomethacin alone. Spray epinephrine should not be used with rectal indomethacin for prevention of post-ERCP pancreatitis. ClincialTrials.gov no: NCT03057769.

Effect of cap-assisted esophagogastroduodenoscopy on examination of the major duodenal papilla: a noninferior, randomized controlled trial.

BACKGROUND: Cap-assisted esophagogastroduodenoscopy (CA-EGD) using a transparent cap fitted to the tip of the scope has emerged as an alternative method for examination of the major duodenal papilla (MDP). However, it remains unclear whether CA-EGD is noninferior to standard duodenoscopy for MDP examination. The aim of this study was to compare the efficacies of the two methods for complete examination of the MDP. METHODS: This prospective, noninferior, randomized controlled study was conducted at two endoscopy centers. Consecutive patients who underwent endoscopic retrograde cholangiopancreatography were randomized (1:1) to undergo CA-EGD or standard duodenoscopy for MDP examination. The primary outcome was complete examination of the MDP, defined as visualization of the upper end, opening, and lower end of the papilla. Secondary outcomes included endoscopic findings and the time taken for the MDP examination. RESULTS: The study was terminated for futility after the interim analysis. A total of 171 patients were randomly allocated to CA-EGD (n = 85) or standard duodenoscopy (n = 86). The baseline characteristics were comparable between the two groups. Complete examination of the MDP was achieved in 58/85 patients (68.2 %) in the CA-EGD group and in 74/86 (86.0 %) in standard duodenoscopy group. The difference in proportions was - 17.81 percentage points (95 % confidence interval [CI] -28.14 to -7.48) by intention-to-treat analysis and - 18.22 percentage points (95 %CI -28.34 to -8.10) by per-protocol analysis, both of which were significantly lower than the noninferiority margin of -5 %, and therefore the noninferiority of CA-EGD could not be confirmed. Examination time was significantly longer with CA-EGD (69.5 [SD 46.4] vs. 33.0 [SD 28.9] seconds; P < 0.001). CONCLUSIONS: Although complete examination of the MDP can be achieved by CA-EGD in most patients, it could not replace duodenoscopy as the standard method for examination of the MDP.

Patient-related factors associated with successful cannulation by trainees during hands-on endoscopic retrograde cholangiopancreatography training.

BACKGROUND AND AIM: Hands-on endoscopic retrograde cholangiopancreatography (ERCP) training is essential for trainees to grasp the technique. Cannulation success rate (CSR) is considered one of the main indicators of competency of trainees. We aimed to investigate whether patient-related factors had an impact on the CSR of trainees. METHODS: A post hoc analysis of data from two multicenter studies (NCT02002650 and NCT03057769) was conducted. Patients aged 18-90 years with native papilla undergoing ERCP were eligible for this study. Only procedures involving trainees in centers strictly following "10-min criteria" for initial cannulation were enrolled. Primary outcome was CSR by trainees. RESULTS: From December 2013 to October 2017, 20 trainees in four centers were involved in initial cannulation in 1044 patients with native papilla. Primary CSR by trainees was 61.0% (436/715), 31.5% (70/222) and 44.9% (48/107) in patients with common bile duct stone (CBDS), biliary stricture (BS) and other indications, respectively (P < 0.001). In multivariate analysis, indication of BS (OR, 0.31; 95% CI, 0.22-0.44; P < 0.001) and presence of type A diverticulum (OR, 1.69; 95% CI, 1.23-2.33; P = 0.001) were both independently associated with cannulation success of trainees. Biliary infection was significantly higher in the BS than in the CBDS group (3.6% vs 0.7%, P = 0.004), whereas other post-ERCP complications were comparable between the two groups. CONCLUSIONS: Indication of BS and the presence of type A diverticulum were independently associated with the success of cannulation by trainees. These findings indicate that greater effort is needed for trainees to improve the ability of cannulation in BS.

Different pattern of risk factors for post-ERCP pancreatitis in patients with biliary stricture.

OBJECTIVE: To identify possible risk factors associated with post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in biliary stricture (BS), common bile duct stone (CBDS) and unselected patients. MATERIALS AND METHODS: Consecutive ERCP patients with native papilla from January 2010 to December 2014 in Xijing Hospital were eligible. Patient-related and procedure-related parameters were collected retrospectively. The primary outcome was PEP. Univariate and multivariate logistic regression were used for data analysis. RESULTS: Totally 3133 unselected patients were included. 695 (22.2%) had BS alone and 1893 (60.4%) had CBDS alone. PEP incidence was higher in BS group compared with CBDS group (6.8% vs. 3.8%, p = .001). Among patient-related factors, duodenal stenosis (OR, 2.74; 95%CI, 1.14-6.59) and hilar stricture (OR, 2.59; 95%CI, 1.41-4.77) were found to be independently associated with PEP in BS group. While female gender (OR, 2.11; 95%CI, 1.20-3.73) and normal total bilirubin (OR, 1.93; 95%CI, 1.13-3.32) were related to PEP in CBDS group. Among procedure-related factors, cannulation time ≥ 5 min (OR, 2.38; 95%CI, 1.06-5.33) and precut (OR, 3.20; 95%CI, 1.35-7.59) was respectively the only independent risk factor for PEP in BS and CBDS group. CONCLUSIONS: Patients with BS and CBDS had different patterns of patient-related and procedure-related risk factors for PEP. The prophylaxis of PEP may need to be individualized based on different indications.

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.

Mechanism study of peptide GMBP1 and its receptor GRP78 in modulating gastric cancer MDR by iTRAQ-based proteomic analysis.

BACKGROUND: Multidrug resistance (MDR) is a major obstacle to the treatment of gastric cancer (GC). Using a phage display approach, we previously obtained the peptide GMBP1, which specifically binds to the surface of MDR gastric cancer cells and is subsequently internalized. Furthermore, GMBP1 was shown to have the potential to reverse the MDR phenotype of gastric cancer cells, and GRP78 was identified as the receptor for this peptide. The present study aimed to investigate the mechanism of peptide GMBP1 and its receptor GRP78 in modulating gastric cancer MDR. METHODS: Fluorescence-activated cell sorting (FACS) and immunofluorescence staining were used to investigate the subcellular location and mechanism of GMBP1 internalization. iTRAQ was used to identify the MDR-associated downstream targets of GMBP1. Differentially expressed proteins were identified in GMBP1-treated compared to untreated SGC7901/ADR and SGC7901/VCR cells. GO and KEGG pathway analyses of the differentially expressed proteins revealed the interconnection of these proteins, the majority of which are involved in MDR. Two differentially expressed proteins were selected and validated by western blotting. RESULTS: GMBP1 and its receptor GRP78 were found to be localized in the cytoplasm of GC cells, and GRP78 can mediate the internalization of GMBP1 into MDR cells through the transferrin-related pathway. In total, 3,752 and 3,749 proteins were affected in GMBP1-treated SGC7901/ADR and SGC7901/VCR cells, respectively, involving 38 and 79 KEGG pathways. Two differentially expressed proteins, CTBP2 and EIF4E, were selected and validated by western blotting. CONCLUSION: This study explored the role and downstream mechanism of GMBP1 in GC MDR, providing insight into the role of endoplasmic reticulum stress protein GRP78 in the MDR of cancer cells.

[Influencing factors for the performance of trainees after hands-on training of endoscopic retrograde cholangiopancreatography].

OBJECTIVE: To evaluate the performance of trainees after finishing hands-on training of endoscopic retrograde cholangiopancreatography (ERCP) at our hospital. METHODS: Questionnaire was distributed to 46 trainees of ERCP training over the past 5 years. And the effects of training duration, case volume and hospital facilities on ERCP performance were examined. RESULTS: A total of 41 valid questionnaires (89.1%) were retrieved. And 34 trainees (82.9%) worked at tertiary medical centers. The mean training duration was 8.9 months. Compared with trainees with less annual ERCP volume (TL) (< 4 cases per month, n = 23), trainees with more volume (TM) (≥ 4 cases per month, n = 18) had a higher rate of successful cannulation and precut by a needle knife (both P < 0.05). More endoscopists could perform ERCP and more duodenoscopes were stocked at hospitals of TM compared with TL (both P < 0.05). The results of trainee self-evaluation showed that the major influencing factors of post-training ERCP performance were hospital supports, handling capacity and case volume. CONCLUSION: After hands-on training, the trainee performance of ERCP is influenced by such multiple factors as handling capacity and hospital supports, etc.

MGr1-Ag/37LRP induces cell adhesion-mediated drug resistance through FAK/PI3K and MAPK pathway in gastric cancer.

It is well known that tumor microenvironment plays a vital role in drug resistance and cell adhesion-mediated drug resistance (CAM-DR), a form of de novo drug resistance. In our previous study, we reported that MGr1-Ag/37LRP ligation-induced adhesion participated in protecting gastric cancer cells from a number of apoptotic stimuli caused by chemotherapeutic drugs. Further study suggested that MGr1-Ag could prompt CAM-DR through interaction with laminin. However, the MGr1-Ag-initiated intracellular signal transduction pathway is still unknown. In this study, our experimental results showed that gastric cancer MDR cell lines mediated CAM-DR through upregulation of Bcl-2 by MGr1-Ag interaction with laminin. Further study found that, as a receptor of ECM components, MGr1-Ag/37LRP may activate the downstream signal pathway PI3K/AKT and MAPK/ERK through interaction with phosphorylated FAK. Moreover, the sensitivity to chemotherapeutic drugs could be significantly enhanced by inhibiting MGr1-Ag/37LRP expression through mAbs, siRNA, and antisense oligonucleotide. According to these results, we concluded that the FAK/PI3K and MAPK signal pathway plays an important role in MGr1-Ag-mediated CAM-DR in gastric cancer. MGr1-Ag/37LRP might be a potential effective reversal target to MDR in gastric cancer.