Development and validation of a prognostic score to identify the optimal candidate for preemptive TIPS in patients with cirrhosis and acute variceal bleeding.

BACKGROUND AND AIM: Baveno VII workshop recommends the use of preemptive TIPS (p-TIPS) in patients with cirrhosis and acute variceal bleeding (AVB) at high- risk of treatment failure. However, the criteria defining "high-risk" have low clinical accessibility or include subjective variables. We aimed to develop and externally validate a model for better identification of p-TIPS candidates. APPROACH AND RESULTS: The derivation cohort included 1554 patients with cirrhosis and AVB who were treated with endoscopy plus drug (n = 1264) or p-TIPS (n = 290) from 12 hospitals in China between 2010 and 2017. We first used competing risk regression to develop a score for predicting 6-week and 1-year mortality in patients treated with endoscopy plus drugs, which included age, albumin, bilirubin, international normalized ratio, white blood cell, creatinine, and sodium. The score was internally validated with the bootstrap method, which showed good discrimination (6 wk/1 y concordance-index: 0.766/0.740) and calibration, and outperformed other currently available models. In the second stage, the developed score was combined with treatment and their interaction term to predicate the treatment effect of p-TIPS (mortality risk difference between treatment groups) in the whole derivation cohort. The estimated treatment effect of p-TIPS varied substantially among patients. The prediction model had good discriminative ability (6 wk/1 y c -for-benefit: 0.696/0.665) and was well calibrated. These results were confirmed in the validation dataset of 445 patients with cirrhosis with AVB from 6 hospitals in China between 2017 and 2019 (6-wk/1-y c-for-benefit: 0.675/0.672). CONCLUSIONS: We developed and validated a clinical prediction model that can help to identify individuals who will benefit from p-TIPS, which may guide clinical decision-making.

Identifying the optimal measurement timing and hemodynamic targets of portal pressure gradient after TIPS in patients with cirrhosis and variceal bleeding.

BACKGROUND & AIMS: The optimal timing of measurement and hemodynamic targets of portacaval pressure gradient (PPG) after transjugular intrahepatic portosystemic shunt (TIPS) placement remain unclear. This study aimed to identify the ideal moment for hemodynamic measurements and the optimal target of PPG in patients undergoing covered TIPS for variceal bleeding. METHODS: Between May 2018 and December 2021, 466 consecutive patients with recurrent variceal bleeding treated with covered TIPS were prospectively included. Post-TIPS PPG was measured immediately (immediate PPG), 24-72 hours (early PPG), and again 1 month (late PPG) after TIPS placement. The agreement among PPGs measured at different time points was assessed by intra-class correlation coefficient (ICC) and Bland-Altman method. The unadjusted and confounder-adjusted effects of PPGs on clinical outcomes (portal hypertensive complications [PHCs], overt hepatic encephalopathy [OHE], further decompensation, and death) were assessed using Fine and Gray competing risk regression models. RESULTS: The agreement between early PPG and late PPG (ICC: 0.34) was better than that between immediate PPG and late PPG (ICC: 0.23, p <0.001). Early PPG revealed an excellent predictive value for PHCs (early PPG≥ vs. <12 mmHg: adjusted hazard ratio 2.17, 95% CI 1.33-3.55, p = 0.002) and OHE (0.40, 95% CI 0.17-0.91, p = 0.030), while immediate PPG did not. Late PPG showed a predictive value for PHC risk but not OHE. By targeting the lowest risk of further decompensation, we identified an optimal hemodynamic target with early PPG ranging from 11 to 14 mmHg that was associated with a decreased risk of OHE and effective prevention of PHC. CONCLUSIONS: PPG measured 24 to 72 hours after TIPS correlates with long-term PPG and clinical outcomes, and a hemodynamic target PPG of 11-14 mmHg is associated with reduced encephalopathy but not compromised clinical efficacy. IMPACT AND IMPLICATIONS: The optimal timing of measurement and hemodynamic targets of portacaval pressure gradient (PPG) after transjugular intrahepatic portosystemic shunt (TIPS) remain unclear. Here we show that post-TIPS PPG measured at least 24 hours but not immediately after the procedure correlated with long-term PPG and clinical events. Thus, PPG measurements taken at least 24 hours after TIPS should be used to guide decision making in order to improve clinical outcomes. Targeting a post-TIPS PPG of 11-14 mmHg or a 20%-50% relative reduction from pre-TIPS baseline measured 24-72 hours after the procedure was associated with reduced encephalopathy but not compromised clinical efficacy. Thus, these criteria could be used to guide TIPS creation and revision in patients with cirrhosis and variceal bleeding undergoing covered TIPS. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, ID: NCT03590288.

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.

Prevalence of Polypharmacy in Elderly Population Worldwide: A Systematic Review and Meta-Analysis.

BACKGROUND: Polypharmacy (PP) is common in elderly population and associated with some adverse clinical outcomes and increases healthcare burdens. We performed this systemic review and meta-analysis to estimate worldwide prevalence of PP and explore associated factors in the elderly. METHODS: The PubMed, Web of Science, Cochrane Library, and Ovid EMBASE databases were searched for studies published until May 30, 2022. We included observational studies representative of general patients aged ≥60 in which PP was defined as multiple drugs ≥5. Studies were excluded if only a particular group of the elderly population (e.g., with diabetes) were included. The primary outcome was the prevalence of PP. Random-effect models were employed to estimate the overall or variable-specific pooled estimates of PP. Secondary outcomes were hyperpolypharmacy (HPP, defined as multiple drugs ≥10) and PP prevalence based on different study years, genders, locations, populations, and so forth. RESULTS: We included 122 original observational studies with an overall population of 57 328 043 individuals in the meta-analysis. The overall prevalence of PP and HPP in the elderly population worldwide was 39.1% (95% confidence interval [CI], 35.5%-42.7%) and 13.3% (95% CI, 10.4%-16.5%), respectively. The prevalence of PP in Europe, Oceania, North America, Asia, and South America was 45.8% (95% CI, 41.5%-50.2%), 45.5% (95% CI, 26.7%-64.3%), 40.8% (95% CI, 29.8%-51.6%), 29.0% (95% CI, 20.0%-38.0%), and 28.4% (95% CI, 24.0%-32.8%), respectively (p < 0.01). Multivariate meta-regressions showed geographical regions of Europe or North America, age ≥70, and residence from nursing homes were independently associated with higher PP prevalence. CONCLUSIONS: Nearly 40% of the elderly population is exposed to PP. The prevalence of PP is significantly higher in elderly individuals aged 70 or older, in developed regions and in nursing homes. It is important to focus on avoiding inappropriate PP in this population to address the growing burden of PP.

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).

Low-dose of magnesium sulfate solution was not inferior to standard regime of polyethylene glycol for bowel preparation in elderly patients: a randomized, controlled study.

BACKGROUND: Large polyethylene glycol (PEG) is a standard regimen for bowel preparation. However, elderly patients suffered from adverse events. This study was to compare the efficacy and safety of oral magnesium sulfate solution (MSS) vs standard PEG in elderly patients undergoing colonoscopy. METHODS: Elderly patients aged 60-90 years, from two endoscopic centers, were enrolled in China. Patients were randomized to take a low dose of MSS or a standard PEG regime in a split-dose regime. The primary endpoint was the proportion of patients with adequate bowel preparation, which was defined as the total Boston Bowel Preparation Scale (BBPS) ≥6 and each segmental BBPS was ≥2. Secondary outcomes included adenoma detection rate (ADR), safety, adverse events, cecal intubation rate, willingness to repeat BP, and so on. RESULTS: 1174 elderly patients were randomly allocated to the MSS group (n = 588) or the standard group (n = 586). Adequate BP was achieved in 94.0% of patients in the MSS group and 92.5% in the control (p = .287). ADR was also comparable between the two groups (43.0% and 39.9%, p = .282). Compared with the standard group, MSS group reported less abdominal discomfort (1.7% vs 6.0%), less nausea (13.6% vs 21.0%) and vomiting (1.2% vs 4.2%). The change in serum potassium levels after preparation in the standard group was significantly lower than that in the MSS group (-0.19 ± 0.08 vs -0.41 ± 0.11, p = .037). CONCLUSIONS: Low dose of MSS was not inferior to the standard PEG regime in terms of bowel preparation quality for elderly patients. Low-dose MSS offered fewer adverse events and better tolerability. It is a preferable choice for the elderly to undergo bowel preparation for colonoscopy. CLINICAL TRIAL REGISTRATION NUMBER: NCT04948567.

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.

Efficacy and safety of ERCP in patients with situs inversus totalis: multicenter case series and literature review.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) in patients with situs inversus totalis (SIT) is rarely understood due to its rarity. Patient position and endoscope manipulation were the main concerns in published case reports. The aim of this study was to investigate the efficacy and safety of ERCP in SIT patients. METHODS: Patients with SIT who underwent ERCP were enrolled in nine endoscopic centers in China. ERCP procedural details and complications in SIT patients were retrieved from electronic medical record. The data was retrospectively analyzed. RESULTS: From 2011 to 2021, totally 14 patients with SIT undergoing ERCP were identified. The mean age was 56.8 years old and the male-female ratio was 5:2. The main indication for ERCP was common bile duct stones (13/14, 92.9%). All procedure were performed by experienced endoscopists. 21.4% (3/14) of patients were under regular position (prone), while 78.6% under modified position (supine, left or right lateral). Difficult cannulation was occurred in 71.4% (10/14) of patients. The rate of successful cannulation was 85.7% (12/14). Complication occurred in 3 patients (3/14, 21.4%), including 1 bleeding, 1 pneumonia and 1 acute myocardial infarction. No post-pancreatitis or death happened. Compared to patients in modified position, those in prone position had numerically less successful cannulations (66.7% vs. 90.9%) and higher adverse events (33.3% vs. 18.2%). CONCLUSIONS: ERCP in patient with SIT is challenging even for experienced endoscopists, modified patient positions might have potential benefits concerning more successful cannulations and less complications. More case experiences are need for comprehensive understanding of ERCP in patients with SIT.

Superiority of a preparation-related model for predicting inadequate bowel preparation in patients undergoing colonoscopy: A multicenter prospective study.

BACKGROUND AND AIM: Three models based on patient-related factors have been developed to predict inadequate bowel preparation (BP). However, the performance of the models seems suboptimal. This study aimed to develop a novel preparation-related model and compare it with the available patient-related models. METHODS: Patients receiving standard BP were prospectively enrolled from five endoscopic centers. Patient-related and preparation-related factors for inadequate BP (defined by segmental Boston Bowel Preparation Scale score < 2) were identified by logistic regression. A preparation-related model was derived and internally validated in 906 patients. The comparisons of models were assessed by discrimination and calibration. The preparation-related model was also externally validated. RESULTS: Several patient-related factors (male and American Society of Anesthesiologists Physical Status Classification System score ≥ 3) and preparation-related factors (drinking-to-stool interval ≥ 3 h, preparation-to-colonoscopy interval ≥ 6 h, and poor rectal effluent) were found to be independently associated with inadequate BP (all P < 0.05). C-statistics was 0.81 for the preparation-related model in the training cohort (n = 604), significantly higher than three available patient-based models (0.58-0.61). Similar results were observed in the validation cohort (n = 302). Calibration curves showed close agreement in the preparation-related model (R2  = 0.315 in the training cohort and 0.279 in the validation cohort). The preparation-related model was externally validated in another 606 patients with C-index of 0.80. CONCLUSIONS: A new preparation-related model (consisting of drinking-to-stool interval ≥ 3 h, preparation-to-colonoscopy interval ≥ 6 h, and poor last rectal effluent) was developed and performed better than three available patient-related models. This easy-to-use model may be a useful decision-support tool on individualized plans in patients undergoing BP.

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).

In vitro and in vivo evaluation of a novel wired transmission magnetically controlled capsule endoscopy system for upper gastrointestinal examination.

BACKGROUND: Magnetically controlled capsule endoscopy (MCCE) has recently increasingly been used for gastric examination. However, the image quality and esophageal observation is suboptimal. We developed a novel wired transmission magnetically controlled capsule endoscopy (WT-MCCE) system and evaluated its feasibility through in vitro and in vivo experiments. METHODS: A plastic stomach model and a pathological upper gastrointestinal model were used to evaluate the performance of WT-MCCE in vitro experiments. Twice of examination in the two in vitro models by WT-MCCE were performed by 5 endoscopists who were experienced in performing wireless capsule endoscopy. The examination of traditional gastroscopy (Olympus, GIF-HQ290) in the pathological upper gastrointestinal model was set as the control. In vivo experiments were performed in a live canine model by 3 endoscopists, in which WT-MCCE was inserted with the assistance of gastroscopy. Measurements included maneuverability, examination time, visualization of gastric mucosa, image quality and diagnostic accuracy. RESULTS: WT-MCCE showed good performance in both in vitro and in vivo experiments with excellent visualization of mucosa (75-100%). The mean operation time is 17.6 ± 2.7 min, 22.3 ± 1.9 min and 29.3 ± 3.4 min in three models, respectively. In pathological upper gastrointestinal model, all lesions, including esophageal varices, one polyp, one foreign body, two gastric ulcers and one duodenal ulcer, were detected by both WT-MCCE and traditional gastroscopy by all endoscopists. For the observation of esophagus and stomach in the canine model, WT-MCCE also showed excellent maneuverability and good image quality. CONCLUSIONS: The novel WT-MCCE system performed well in evaluating upper gastrointestinal landmarks and lesions in two in vitro models, and showed good performance in a canine model. WT-MCCE may be potentially useful for diagnosis of esophageal and gastric diseases.

Nonradiation-to-endoscopist ERCP is non-inferior to standard ERCP.

BACKGROUND: Radiation exposure is inherently involved in endoscopic retrograde cholangiopancreatography (ERCP), which could cause radiation-induced injury to endoscopists with long-term exposure. Nonradiation ERCP has been applied to pregnant patients. Conceivably, the same techniques could be used to benefit endoscopists. This study was designed to evaluate the effectiveness and safety of nonradiation-to-endoscopist (NRE) ERCP, compared with standard ERCP. METHODS: A retrospective, single-center study was conducted from August 2010 to December 2015. Patients aged 18-90 years and with choledocholithiasis (< 15 mm) or distal biliary stricture were eligible. Pre-ERCP evaluation with magnetic resonance cholangiopancreatography was mandatory. To overcome selection bias, we performed 1:2 match using propensity score matching (PSM) between NRE and standard groups. The primary endpoint was overall ERCP success rate. Secondary endpoints were cannulation success rate, stone clearance rate, complication rate, and duration of hospitalization. RESULTS: A total of 329 patients met inclusion criteria. After PSM, 73 patients were included in the NRE group and 146 in the standard group. The ERCP overall success rate for NRE and standard groups was equivalent (94.5% vs. 93.2%, P = 0.70). There was no difference in cannulation success rates between the two groups (95.6% vs. 97.8%, P = 0.39). A total of 88.3% of patients in the NRE group and 93.9% of patients in the standard group had stones cleared at initial ERCP (P = 0.57). No difference in overall stone clearance rate between the two groups (95.0% vs. 93.9%, P = 0.77) was found after second ERCP. The complication rate (1.4% vs. 1.4%, P = 1.00) and hospital duration (8.3 ± 5.1 vs. 10.2 ± 8.8 days, P = 0.07) were not different between the two groups. CONCLUSION: Although technically demanding, NRE-ERCP is both safe and feasible in selected patients compared with standard ERCP.

Water-assisted colonoscopy: an international modified Delphi review on definitions and practice recommendations.

BACKGROUND AND AIMS: Since 2008, a plethora of research studies has compared the efficacy of water-assisted (aided) colonoscopy (WAC) and underwater resection (UWR) of colorectal lesions with standard colonoscopy. We reviewed and graded the research evidence with potential clinical application. We conducted a modified Delphi consensus among experienced colonoscopists on definitions and practice of water immersion (WI), water exchange (WE), and UWR. METHODS: Major databases were searched to obtain research reports that could potentially shape clinical practice related to WAC and UWR. Pertinent references were graded (Grading of Recommendations, Assessment, Development and Evaluation). Extracted data supporting evidence-based statements were tabulated and provided to respondents. We received responses from 55 (85% surveyed) experienced colonoscopists (37 experts and 18 nonexperts in WAC) from 16 countries in 3 rounds. Voting was conducted anonymously in the second and third round, with ≥80% agreement defined as consensus. We aimed to obtain consensus in all statements. RESULTS: In the first and the second modified Delphi rounds, 20 proposed statements were decreased to 14 and then 11 statements. After the third round, the combined responses from all respondents depicted the consensus in 11 statements (S): definitions of WI (S1) and WE (S2), procedural features (S3-S5), impact on bowel cleanliness (S6), adenoma detection (S7), pain score (S8), and UWR (S9-S11). CONCLUSIONS: The most important consensus statements are that WI and WE are not the same in implementation and outcomes. Because studies that could potentially shape clinical practice of WAC and UWR were chosen for review, this modified Delphi consensus supports recommendations for the use of WAC in clinical practice.

Targeted imaging of esophageal adenocarcinoma with a near-infrared fluorescent peptide.

BACKGROUND: Targeted optical imaging offers a noninvasive and accurate method for the early detection of gastrointestinal tumors, especially for flat appearances. In our previous study, a sequence of SNFYMPL (SNF) was identified as a specific peptide to bind to esophageal carcinoma using phage-display technology. This study aimed to evaluate the tumor-targeting efficacy of Cy5.5-conjugated SNF probe for imaging of esophageal carcinoma in vitro and in vivo. METHODS: The SNF-Cy5.5 probe was synthesized and then identified using High Performance Liquid Chromatography (HPLC) and mass spectrometry (MS). Confocal fluorescence imaging and Flow cytometry analysis were performed to evaluate the binding specificity and the receptor binding affinity of SNF-Cy5.5 to OE33. In vivo imaging was performed to evaluate the targeting ability of SNF-Cy5.5 to esophageal carcinoma. RESULTS: The confocal imaging and flow cytometry analysis showed that SNF-Cy5.5 bound specifically to the plasma membrane of OE33 cells with a high affinity. In vivo, for non-block group, SNF-Cy5.5 probe exhibited rapid OE33 tumor targeting during 24 h p.i. and excellent tumor-to-background contrast at 2 h p.i. For the block group, SNF-Cy5.5 was not observed in the mice after 4 h p.i. Ex vivo imaging also revealed that a higher fluorescent signal intensity value of the tumors was clearly observed in the non-block group than that in the block group (2.6 ± 0.32 × 109 vs. 0.8 ± 0.08 × 109, p < 0.05). CONCLUSIONS: SNF-Cy5.5 was synthesized and characterized with a high efficiency and purity. The higher affinity, specificity, and tumor targeting efficacy of SNF-Cy5.5 were confirmed by in vitro and in vivo tests. SNF-Cy5.5 is a promising optical probe for the imaging of esophageal adenocarcinoma.

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.

Comparison of endoscopic bilateral metal stent drainage with plastic stents in the palliation of unresectable hilar biliary malignant strictures: Large multicenter study.

BACKGROUND: Endoscopic stenting to manage malignant hilar biliary obstruction has no consensus regarding the optimal stenting strategy. In this multicenter study, we compared transpapillary parallel-style bilateral metal stenting with bilateral plastic stenting, and evaluated short- and long-term outcomes. METHODS: We recruited 262 consecutive patients (Bismuth classification types II-IV) who underwent either bilateral metal or plastic stenting as primary therapy at four tertiary centers. To overcome selection bias, we performed 1:1 propensity score matching. Our primary outcome was overall survival. RESULTS: After propensity score matching, each group comprised 96 patients, with no significant differences in any baseline characteristics. The median survival was significantly longer in the metal stenting group than in the plastic stenting group (7.2 months [95% CI 6.0-8.5] vs. 4.1 months [95% CI 2.9-5.3]; P = 0.015). The clinical success rates were significantly higher in the metal stenting group than in the plastic stenting group (99.0% vs. 71.9%, respectively; P < 0.001), and lower post-procedure cholangitis incidence (7.3% vs. 26.0%; P < 0.001), longer median symptom-free stent patency (9.2 months [95% CI 7.6-10.6] vs. 4.8 months [95% CI 4.2-5.3]; P < 0.001), and fewer total interventions (1.3 ± 0.6 vs. 2.0 ± 1.4; P < 0.001). In multivariate Cox analysis of the overall survival, metal stenting (HR 0.589, P = 0.002), hilar cholangiocarcinoma (HR 0.419, P = 0.009), and adjuvant treatment (HR 0.596, P = 0.006) were independent predictors of death. CONCLUSIONS: Endoscopic therapy using bilateral metal stenting is superior to bilateral plastic stenting, with prolonged overall survival, higher clinical success, and longer stent patency in patients with advanced hilar biliary malignancies.

Optimal stent placement strategy for malignant hilar biliary obstruction: a large multicenter parallel study.

BACKGROUND AND AIMS: The endoscopic management of malignant hilar biliary obstruction (MHBO) remains extremely challenging without universal consensus. For the first time, we compared 4 major modalities aiming to determine the optimal strategy. METHODS: We reviewed 1239 patients with advanced MHBO who underwent endoscopic stent placement as the primary treatment in 4 tertiary centers. Among them, 633 eligible patients were identified and classified into 4 groups: bilateral metal stent placement (BMS), unilateral metal stent placement (UMS), bilateral plastic stent placement (BPS), and unilateral plastic stent placement (UPS). The outcomes were compared before and after propensity score matching (PSM). RESULTS: After PSM, 87, 97, 91, and 81 patients in the BMS, UMS, BPS, and UPS groups, respectively, were matched. The clinical success rates were 98.9%, 83.5%, 71.4%, and 65.4% in the BMS, UMS, BPS, and UPS groups (P < .001), respectively. The postprocedural cholangitis rates were 8.0%, 17.5%, 26.4%, and 29.6% (P = .002), respectively. The median symptom-free stent patency was 9.6, 6.8, 4.6, and 4.2 months (P < .001), respectively. The mean number of interventions required was 1.2 ± 0.5, 1.7 ± 0.8, 2.0 ± 1.4, and 1.9 ± 1.3 (P < .001), respectively. The median (95% confidence interval) overall survival (OS) was 7.1 (6.0-8.2), 4.4 (3.8-4.9), 4.1 (2.9-5.2), and 2.7 (1.8-3.7) months (P = .001), respectively. Compared with plastic stent placement, metal stent placement achieved higher success in all outcome parameters (P ≤ .001). Bilateral stent placement was superior to unilateral stent placement in terms of clinical success (P = .024), stent patency (P = .018), and OS (P = .040). CONCLUSIONS: If technically possible, dual metal stent placement is a preferred palliation for inoperable MHBO, and unilateral metal stent placement is the second option.

Water Exchange (WE) and Quality Improvement-Enhanced Advanced Adenoma Detection: A Pooled Data Analysis of 6 Randomized Controlled Trials.

INTRODUCTION: Advanced adenomas (≥10 mm in diameter, >25% villous, or high-grade dysplasia), a marker of colorectal cancer risk, are used to stratify patients for closer surveillance. Modern accessories, endoscopes, and age-adjusted evaluation have variable impacts on the advanced adenoma detection rate (AADR). In 1 randomized controlled trial (RCT) comparing air insufflation (AI) with water exchange (WE), the right colon AADR was significantly increased by WE. Four network meta-analyses reported that WE significantly increased overall adenoma detection rate (ADR), but the impact on AADR was not addressed. AIM: The aim of this study was to test the hypothesis that WE significantly increased AADR compared with AI. METHOD: Six Clinicaltrial.gov-registered RCTs were reported by a group of WE investigators. Data including AADR (primary outcome) and overall ADR (secondary outcome) were pooled. RESULTS: A total of 5407 patients were randomized to AI (2699) and WE (2708). Compared with AI, WE significantly increased AADR (5.7% vs. 8.3%, P=0.001) and overall ADR (20.9% vs. 27.4%, P=0.001). CONCLUSIONS: In contrast to published reports, which showed variable impacts on AADR, WE was consistent in increasing AADR in 6 reported RCTs. The pooled data confirm that the impact of WE in increasing AADR was significant. The significantly enhanced overall ADR indicated that WE provided a higher quality outcome than AI. The significant improvement in AADR confirmed WE to be clinically relevant and has finally arrived as a timely addition to colorectal cancer prevention programs.