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.

Background: Horizontal duodenal papilla (HDP) is not an uncommon ectopic major papilla. The impact of HDP on the occurrence of pancreaticobiliary diseases remains unclear. Here, we explored the associations in patients who underwent magnetic resonance cholangiopancreatography (MRCP). Methods: Consecutive patients who underwent MRCP at Xijing Hospital (Xi'an, China) between January 2020 and December 2021 were eligible. Patients were divided into HDP and regular papilla (RP) according to the position of the major papilla. The primary outcome was the proportion of congenital pancreaticobiliary diseases. Results: A total of 2,194 patients were included, of whom 72 (3.3%) had HDP. Compared with the RP group (n = 2,122), the HDP group had a higher proportion of congenital pancreaticobiliary diseases, especially choledochal cyst (CC) or anomalous pancreaticobiliary junction (APBJ) (6.9% vs 1.4%, P = 0.001). More gallbladder cancer (6.9% vs 1.2%, P < 0.001) and pancreatic cysts (27.8% vs 16.3%, P = 0.01) were also identified in the HDP group. Morphologically, the HDP group had a longer extrahepatic bile duct (8.4 [7.6-9.3] cm vs 7.2 [6.5-8.1] cm, P < 0.001), and larger angles between the common bile duct-duodenum and pancreatic duct-duodenum. Multivariate analysis showed that the presence of HDP was an independent risk factor for gallbladder cancer. Conclusions: This study confirmed that HDP was not rare in patients underwent MRCP. A higher prevalence of congenital pancreaticobiliary malformations (especially CC or APBJ), gallbladder cancer and pancreatic cysts was observed in patients with HDP, as well as distinctive morphologic features.

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).

Background:Moderate-to-severe post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis contributes to most of the poor outcomes of patients with post-ERCP pancreatitis (PEP). However, it remains unclear which part of the patient is more vulnerable to moderate-to-severe PEP (MS PEP). In this study, we aimed to identify the risk factors independently associated with MS PEP.Methods:Consecutive patients with native papilla who had undergone ERCP were included in this study. The patient-related and procedure-related variables were retrieved from a prospectively maintained ERCP database. The primary outcome was the incidence of PEP. MS PEP was defined as a prolonged hospital stay of ≥4 days (as per the Cotton criteria) or the presence of organ failure (as per the revised Atlanta criteria). A logistic regression analysis was conducted to identify the risk factors.Results:A total of 6,944 patients with native papilla who had undergone elective ERCP from January 2010 to February 2022 were included in this study. Among these 6,944 patients, 362 (5.2%) patients developed PEP. Among these 362 patients, 76 (1.1%) or 17 (0.2%) had MS PEP as per the Cotton criteria and the revised Atlanta criteria, respectively. The logistic analysis revealed that the independent risk factors for overall and mild PEP were similar, and included being female and inadvertent pancreatic duct (PD) cannulation. A total cannulation time >15 min was also found to be an independent risk factor for MS PEP as defined by both the Cotton criteria and the revised Atlanta criteria.Conclusions:This study found that female patients and those who had inadvertent PD cannulation were at risk of mild PEP. A total cannulation time >15 min was also found to be a risk factor for developing MS PEP.

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.

Objective To systematically review the safety and effectiveness of tension-free vaginal tape (TVT), transobturator tape (TOT), and transvaginal tension-free vaginal tape-obturator (TVT-O) in the treatment of stress urinary incontinence (SUI). Methods The PubMed, Embase, The Cochrane Library, Web of Science, WanFang Data, and CNKI were electronically searched. A total of 22 trials involving 3709 patients were included. Results The objective cure rate was better with TVT than with TOT and TVT-O. The incidence of postoperative thigh/groin pain was lower with TVT than with TOT and TVT-O, but the incidence of dysuria was higher with TVT than with TVT-O. The incidence of lower urinary tract infection was higher with TVT than with TOT. Conclusion Tension-free vaginal tape may have a better outcome compared to TOT and TVT-O, but the risk of dysuria and lower urinary tract infection is higher with SUI.

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 (rho), 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 (rho = 0.64) and fairly correlated with the other four scores (rho = 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).

BACKGROUND Double-balloon, single-balloon, and spiral enteroscopy（DBE, SBE, and SE） have revolutionized the management of intestinal diseases. However, evidence about efficacies of these methods is lacking. We aimed to conduct a meta-analysis comparing the clinical outcomes among DBE, SBE, and SE.METHODS We searched randomized controlled trials and prospective studies in MEDLINE,Pub Med, EMBASE, Cochrane Library, and Chinese CQVIP database. Studies referencing the comparison of at least two of these three methods were included.Primary outcome was diagnostic yield. Other outcomes were therapeutic yield,total enteroscopy, examination time, time to maximum insertion, and depth of maximal insertion（DMI）.RESULTS Eleven studies including 727 patients were identified: DBE vs SE（n = 6）, DBE vs SBE（n = 4）, and SBE vs SE（n = 1）. The diagnostic and therapeutic yields did not differ significantly when comparing DBE with SE [odds ratio（OR） = 1.19, 95%confidence interval（CI）: 0.68-2.08; OR = 1.17, 95%CI: 0.61-2.23] and DBE with SBE （OR = 0.85, 95%CI: 0.55-1.33; OR = 1.71, 95%CI: 0.64-4.60）. Total enteroscopy,examination time, time to maximum insertion, and DMI were similar between SBE and DBE. DBE was superior to SE with regard to DMI [mean difference（MD）= 36.76, 95%CI: 5.09-68.43], with longer time to maximum insertion（MD = 15.14,95%CI: 12-18.27） and examination time（MD = 12.98, 95%CI: 9.57-16.38）.CONCLUSION DBE and SBE have similar clinical outcomes. Compared with DBE, SE seems to have similar diagnostic and therapeutic yields, but shorter procedural time in cost of less depth of insertion. SE needs further evaluation vs SBE. DBE is recommended for complete enteroscopy.

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.

Constipation is a common reason of poor bowel preparation, which negatively influences the quality of colonoscopy. Risk factors for inadequate bowel preparation in constipated patients remain unclear. This study aimed to investigate the high-risk factors that might influence the quality of bowel preparation in patients with functional constipation. Consecutive patients with functional constipation who underwent colonoscopy between June 2016 and April 2017 were enrolled. A standard split dose of 4 l polyethylene glycol was used for bowel preparation. Patient- and procedure-related parameters were recorded. The primary outcome was an adequate rate of bowel preparation. Risk factors for inadequate bowel preparation were screened by multivariate logistic regression analysis. A total of 199 patients were included. Adequate bowel preparation was found in 62.8% (125/199) of patients. At multivariate analysis, Bristol stool form scale (BSFS) 1 [odds ratio (OR) 2.73, 95% confidence interval (CI) 1.26–5.90; P = 0.011], rectal pain score during defecation < 2 (OR 4.14, 95% CI 1.22–13.97; P = 0.022), and starting-to-defecation interval ≥ 4 h (OR 3.83, 95% CI 1.34–10.91; P = 0.012) were risk factors for inadequate bowel preparation in patients with constipation. For patients with no, 1, 2, or 3 risk factors, the rates of inadequate bowel preparation were 11%, 23%, 49%, and 65%, respectively. With the standard preparation regime, > 1/3 of patients with functional constipation had inadequate bowel cleansing. BSFS 1, rectal pain score during defecation < 2, and starting-to-defecation interval ≥ 4 h were identified as independent risk factors for inadequate bowel preparation in constipated patients. ClinicalTrials.gov number NCT02842411.

Urinary incontinence (UI) is known as a distressing condition particularly among older adults, and negatively associated with health-related quality of life in both males and females. Prelamin A accumulation has been found in all progeroid laminopathies and is obviously linked to cell and organism aging. Therefore, this study was expected to investigate the effect of prelamin A on detrusor on UI. Prelamin A expression in clinical and animal samples was detected. To investigate the degree of prelamin A accumulation and detrusor calcification/aging, the detrusor cells were subcultured separately into low and high passage. The low-passage subculture cells were treated with transfection of overexpressed prelamin A plasmid, and transfection of overexpressed prelamin A plasmid and application of farnesyl transferase inhibitor (FTIs) H-9279, respectively. Zmpste24, Icmt and lamin A/C expression were detected to explore how prelamin A affected detrusor calcification/aging. Prelamin A was overexpressed in aged detrusor cells, indicating prelamin A expression was positively related to the age of subjects. The degree of prelamin A accumulation and detrusor calcification/aging was higher in aged rats and high passage subculture cells. Zmpste24, Icmt and lamin A/C were poorly expressed in cells transfected with overexpressed prelamin A, as well as cell proliferation activity decreased and calcium deposition and apoptotic rate increased.Furthermore, we also found that the effect of overexpressed prelamin A was lost when cells were treated with H-9279. These findings provide evidence that prelamin A overexpression impairs degradation of its farnesylated form, thus causing prelamin A accumulation which induces detrusor calcification/aging in UI.

Abstract Background: Accumulating evidence has indicated that the dysregulation of immunological environment has an important role in the pathogenesis of myelodysplastic syndromes (MDS). The previous studies about the levels of the inflammatory cytokines in MDS, such as TNF-α, IFN-γ, IL-6, IL-8, and IL-17, have yielded controversial results. Thus, we performed a meta-analysis to assess the levels of these inflammatory cytokines in MDS. Methods: A systematic search in PubMed, MEDLINE, Cochrane Library, Web of Science, CNKI, and CBM was conducted to find eligible studies. Meta-analyses were performed using STATA 12.0 for Windows. Heterogeneity between included studies was assessed by I2 test. We chose SMD as the summary statistic. Results: A total of 697 individuals from 11 studies were included in this study. Our results suggest the levels of TNF-α, IL-6, IL-8 were significantly higher in MDS patients compared with controls, SMD and 95%CI was 1.48 (0.60, 2.36), 0.71 (0.16, 1.25) and 0.69 (0.28, 1.09), respectively. Moreover, the levels of IL-17 have decreased in the high-risk MDS, the SMD and 95% CI was 2.96 (0.78, 5.15). Conclusion: A close association between immunological microenvironment disorders and the pathogenesis of MDS was revealed in this meta-analysis. More importantly, the profiles of inflammatory cytokines appear to change along the progression of the disease.

Background Second-line treatment for urothelial carcinoma (UC) patients is used if progression or failure after platinum-based chemotherapy occurs or if patients are cisplatin-unfit. However, there is still no widely accepted treatment strategy. We aimed to analyze the effectiveness and safety of second-line treatment strategies for UC patients. Methods The PubMed, Embase, and Cochrane databases were searched for randomized controlled trials (RCTs) that included UC patients who were cisplatin-ineligible or unfit up to April 19, 2019. The primary outcomes were progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). Results Thirteen trials that assessed 3502 UC patients were included. This study divided the network comparisons into three parts. The first part contained studies comparing taxanes and other interventions; the second part assessed investigator’s choice chemotherapy (ICC)-related comparisons; and the third part assessed best support care (BSC). In the OS results of the first part, pembrolizumab (87.5%), ramucirumab plus docetaxel (74.6%), and atezolizumab (71.1%) had a relative advantage. Pembrolizumab also had advantages in ORR and severe adverse effect (SAE) results. Vinflunine and ramucirumab plus docetaxel had a relatively high surface under the cumulative ranking curve (SUCRA) rank by exploratory cluster analysis. Conclusions This study concluded that atezolizumab and pembrolizumab are superior to other treatments, mainly in OS results, but no treatment confers a significant advantage in PFS. Pembrolizumab still has relative advantages in ORR and SAE results compared to ICC. Due to limitations, more studies are necessary to confirm the conclusions.

Constipation is a common reason of poor bowel preparation, which negatively influences the quality of colonoscopy. The risk factors associated with inadequate bowel preparation in constipated patients remains unclear. The aim of this study was to investigate the high-risk factors which might influence the quality of bowel preparation in patients with functional constipation. In this multicenter, prospective cohort study, consecutive patients with functional constipation who underwent colonoscopy between May 2016 and April 2017 were enrolled. Standard split-dose of 4 Liter (L) polyethylene glycol (PEG) was used for bowel preparation. Patient-related and procedure-related parameters were recorded. The primary outcome was adequate rate of bowel preparation, defined as Boston Bowel Preparation Scale (BBPS) ≥6 with each segment ≥2. Risk factors for inadequate bowel preparation were screened by multivariate logistic regression analysis. A total of 199 patients with functional constipation were included. 78.4% of them were female. Adequate bowel preparation was found in 62.8% (125/199) of patients. At multivariate analysis, Bristol stool form scale (BSFS) 1 (odds ratio [OR] 2.25, 95% confidence interval [CI] 1.11-4.56; P = 0.008), no or mild pain during defecation (OR 4.14, 95% CI 1.22-13.97; P=0.022), and starting-to-defecation interval more than 4h (OR 3.10, 95% CI 1.17-8.22; P=0.023) were independent risk factors for inadequate bowel preparation in patients with constipation. For patients with non-, 1, 2 or 3 risk factors, the rates of inadequate bowel preparation were 11%, 23%, 49%, and 65% respectively (P＜0.001). With standard preparation regime, more than 1/3 of patients with functional constipation had inadequate bowel cleansing. BSFS 1, no or mild pain during defecation, and starting-to-defecation interval more than 4h were identified as independent risk factors for inadequate bowel preparation in constipated patients.Tabled 1Multivariate analysis of the association between potentially significant factors and inadequate bowel preparationInadequate rate, n (%)OR (95% CI)P valueUnmarried6/9 (66.7%)4.24 (0.87-20.81)0.075Past alcohol intake1/11 (9.1%)0.17 (0.02-1.52)0.113Duration of constipation ≥4 years44/130 (33.8%)0.55 (0.26-1.16)0.119BSFS score 150/110 (45.5%)2.25 (1.11-4.56)0.024No or mild pain during defecation70/174 (40.2%)4.14 (1.22-13.97)0.022Stools ≤3 times per week31/104 (29.8%)1.31 (0.65-2.64)0.45Using purgatives ≥2 times per week22/77 (28.6%)0.87 (0.42-1.78)0.695Starting-to-defecation interval ≥4h20/32 (62.5%)3.10 (1.17-8.22)0.023Vomiting19/36 (52.8%)2.89 (0.91-14.32)0.113Nausea41/84 (48.8%)1.56 (0.79-3.05)0.199Stools ≤2 times after 1st PEG23/45 (51.1%)1.37 (0.60-3.13)0.454BSFS, Bristol stool form scale; PEG, polyethylene glycol; OR, odds ratio; CI, confidence interval. Open table in a new tab

AIM:Water-assisted colonoscopy (water exchange [WE] and water immersion [WI]) has been shown to improve the adenoma detection rate. However, few studies have compared these two methods head-to-head. Thus, we conducted a network meta-analysis to integrate both direct and indirect evidence comparing the effectiveness of these two procedures. METHOD:We searched PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials for original papers and abstracts published up to March 2018. Randomized controlled trials (RCTs) reporting data in accordance with the eligibility criteria were included in this study. We performed a Bayesian random effects network meta-analysis with mixed comparisons. RESULTS:Twenty-nine studies (n = 11464 patients) including 6 direct and 23 indirect comparisons were included in this network meta-analysis. There was a statistically significant difference in the efficacy of adenoma detection when WE was compared with WI (risk ratio [RR]: 1.2, 95% credible interval [CrI]: 1.1-1.3), air insufflation (AI; RR: 1.3, 95% CrI: 1.1-1.4), and carbon dioxide (CO2) insufflation (RR: 1.2, 95% CrI: 1.1-1.5). The different methods were ranked in order from the most to least effective in adenoma detection as follows: WE, WI, AI, and CO2. Moreover, although there were no significant differences in pain scores, willingness to repeat, caecal intubation rate, or total procedure time between WI and WE colonoscopy, WE required a longer caecal intubation time than WI. CONCLUSION:This network meta-analysis supposes that WE may be superior to WI in detecting adenomas during colonoscopies without affecting other technical features or patient acceptance.

Background: Evidence regarding the benefit of therapy to prevent the post-polypectomy recurrence of colorectal adenoma is limited. Endoscopic recurrence is the main outcome according to an evaluation of trials involving recurrence prevention.Aim: To estimate the recurrence rates of post-polypectomy colorectal adenoma in placebo-controlled arms of randomized clinical trials and to identify the prognostic factors influencing these rates.Methods: We combined data from all randomized controlled trials evaluating therapies for colorectal adenoma using placebo from 1988 to 2016. The data were combined in a random-effects model. Primary outcomes were endoscopic adenoma and advanced adenoma recurrence of colorectal adenoma.Results: The pooled estimates of the adenoma recurrence rates were 37% (95% confidence interval [CI], 33%-41%; range, 33%-52%) at 1 year, 47% (95% CI, 41%-54%; range, 46%-51%) at 2 years, 41% (95% CI, 33%-48%; range, 20%-61%) at 3 years, 48% (95% CI, 38%-57%; range, 37%-53%) at 4 years, and 60% (95% CI, 52%-68%; range, 48%-68%) at 5 years. The pooled estimates of the advanced adenoma recurrence rates were 10% (95% CI, 6%-15%; range, 7%-13%) at 1 year, 12% (95% CI, 8%-16%; range, 3%-19%) at 3 years, 14% (95% CI, 10%-18%; range, 13%-16%) at 4 years, and 14% (95% CI, 10%-19%; range, 9%-21%) at 5 years. Significant heterogeneity among the randomized clinical trials (P < 0.001) was observed for each recurrence rate.Conclusions: This meta-analysis confirms the heterogeneity of recurrence rates among post-polypectomy colorectal adenoma patients who received placebo. No single design variable was identified that might explain the heterogeneity.