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.

Diagnostic Efficacy of a Novel Rotating Brush for Endoscopic Sampling of Malignant Biliary Strictures: A Multicenter Prospective Study.

INTRODUCTION: Although cytologic examination of biliary stricture brushings obtained by endoscopic retrograde cholangiopancreatography is commonly used for diagnosing malignant biliary strictures (MBSs), it has low sensitivity. Several new brushes have capabilities that are still being debated. We have developed a novel brush working from conventional back-and-forth movement to rotation in situ (RIS) that may be more efficient for MBS sampling. We aimed to compare the MBS detection sensitivity of our RIS brush with that of the conventional brush. METHODS: In this multicenter prospective study, we enrolled patients who underwent endoscopic retrograde cholangiopancreatography for suspected MBSs involving biliary stricture brushings obtained using our RIS brush. The historical control group consisted of the 30-brushing arm of our previous randomized trial (patient inclusion, 2018-2020) that used the study design in the same centers and with the same endoscopists as were used in this study. The primary outcome was to compare the sensitivity and specificity of detecting MBSs by cytologic evaluation of biliary stricture brushings between the 2 groups. RESULTS: We enrolled 155 patients in the intent-to-treat analysis. Using the same number of brushing cycles, the RIS brush showed a higher sensitivity than the conventional brush (0.73 vs 0.56, P = 0.003). In per-protocol population, the sensitivity was also higher in the RIS brush group than in the conventional brush group (0.75 vs 0.57, P = 0.002). Multivariate analysis revealed that the RIS brush was the only predictive factor for MBS detection. No significant differences were observed in procedure-related complications between the 2 groups. DISCUSSION: The RIS brush was a promising tool for effective and safe MBS sampling and diagnosis. Further randomized studies are warranted to confirm our results (Chictr.org.cn, identifier: ChiCTR2100047270).

Combining brushing cytology with simultaneous vacuum aspiration in suspicious biliopancreatic malignancies: A multicenter propensity score-matched study (with video).

BACKGROUND: Brush cytology during endoscopic retrograde cholangiopancreatography (ERCP) is a standard approach in diagnosing biliopancreatic strictures, with yet unsatisfying sensitivity. AIMS: We brought additional simultaneous vacuum aspiration to brushing process and re-evaluate the diagnostic performance. METHODS: This multi-centered retrospective study was conducted in three tertiary centers. Consecutive patients with biliopancreatic strictures were identified. The patients were divided into two arms: the conventional arm (CA) receiving general brushing approach, and the modified arm (MA) being treated with additional vacuum aspiration when performing bushing. The 1:1 propensity-score matching was implemented to tackle the selective biases. RESULTS: A total of 555 patients were identified and 200 patient pairs (193 males, 207 females, with a mean age of 68.1 ± 13.1 years.) fell into the ultimate evaluation. A final diagnosis of malignant stricture was established in 243 patients. The diagnostic yield of the MA group was substantially better than that of the CA group, whether "suspicious malignancies" were considered malignancies or not. The rates of sensitivity, specificity and accuracy were 46.2%, 100%, 68.0% in the MA group, and 15.3%, 98.7%, and 47.0% in the CA group respectively. CONCLUSIONS: Brushing accompanied by simultaneous vacuum aspiration at ERCP improves the diagnostic yield in suspicious biliopancreatic malignancies.

Endobiliary radiofrequency ablation for unresectable malignant biliary strictures: Survival benefit perspective.

Endobiliary radiofrequency ablation (RFA) is an emerging technique in recent years for palliating malignant biliary strictures (MBS) unsuitable for surgical resection. To date, many clinical studies have shown good feasibility and safety of this therapy; but controversy exists on whether survival can be improved in patients with advanced MBS. A comprehensive review of the available literature demonstrates that RFA can effectively prolong the overall survival of extrahepatic cholangiocarcinoma (CCA) and ampullary cancer, especially in cases without distant metastasis. However, this topical therapy does not confer a survival benefit in patients with nonprimary bile duct malignancies, such as liver, gallbladder, or pancreatic cancers. Biliary RFA combined with systemic chemotherapy may have a synergistic effect on the outcome of inoperable CCA. Patients with locally advanced tumors rather than distant metastasis might benefit more from this combination therapy.

More Endoscopy-Based Brushing Passes Improve the Detection of Malignant Biliary Strictures: A Multicenter Randomized Controlled Trial.

INTRODUCTION: Endoscopic biliary brushing is the most common method used for sampling in patients with malignant biliary strictures (MBSs); however, its sensitivity is relatively low. There is still no consensus on endoscopy-based biliary brushing, although brushing 10 times in 1 specimen is routinely performed. This study was designed to compare the sensitivity of brush cytology for 10, 20, or 30 brushing times of a pass in 1 specimen in patients with MBSs. METHODS: In this multicenter, prospective, randomized controlled study, patients who underwent endoscopic retrograde cholangiopancreatography for suspected MBSs were enrolled. Patients were randomly assigned to receive 10, 20, and 30 brushing times of a pass. The primary outcome was to compare the sensitivity of brush cytology among the 3 groups. Patients were prospectively followed up for 6 months after endoscopic brushing for malignancy diagnosis. RESULTS: A total of 443 patients were enrolled for intention-to-treat analysis (147, 148, and 148 patients in the 10-times, 20-times, and 30-time groups, respectively). The 3 groups were similar in baseline characteristics. The sensitivity of brush cytology was 38%, 47%, and 57% in the 10-times, 20-times, and 30-times groups, respectively, and the 30-times group showed significantly higher sensitivity than the 10-times group (P = 0.001). The multivariate analysis revealed that stricture length and the number of brushing passes were significant factors for the detection of biliary malignancy. No significant differences were observed in procedure-related complications among the 3 groups. DISCUSSION: Brushing 30 times could increase the diagnostic sensitivity without increasing complications and seems to be preferred for the endoscopic sampling and diagnosis of MBSs (chictr.org.cn, identifier: ChiCTR1800015978).

Long Slimmer Metal Stent Is Feasible and Effective for Endoscopic Dual Stent-by-Stent Placement in Malignant Hilar Biliary Stricture.

BACKGROUND: Bilateral endoscopic biliary stenting remains technically challenging, which limits its wider clinical application. AIMS: We have developed a novel long (10-12 cm) and slimmer (6 mm) self-expanded metal stent. The aim of this study was to evaluate the feasibility, efficacy, and safety of the new metal stent for palliative treatment of malignant hilar biliary strictures (MHBS). METHODS: This retrospective study of prospectively collected data included 45 patients with unresectable malignant hilar biliary strictures of Bismuth type II or higher. A pair of long slimmer metal stents were sequentially placed into the intrahepatic duct using the stent-by-stent mode. The success rate and short- and long-term clinical outcomes were observed. RESULTS: The technical success rate was 100%, with a mean procedure time of 43.7 ± 11.5 min. The clinical success was achieved in 44 patients (97.8%). Early adverse events included mild acute pancreatitis (n = 2) and cholangitis (n = 3). Later cholangitis occurred in 14 of the 45 patients due to stent occlusions. The median stent patency was 260 days (95% CI 228.3-291.7). Stent malfunctions occurred in 23 of the 45 patients, and 15 of them received bilateral endoscopic plastic stents placements. The technical success for the re-intervention was 100% with the mean procedure time of 24.3 ± 4.5 min. The median overall survival of the whole group was 229 days (95% CI 171.2-286.8). CONCLUSIONS: The long slimmer metal stent for bilateral endoscopic stent-by-stent placement proved to be safe, feasible, and effective for MHBS and facilitates endoscopic re-intervention as well.

Effect of endoscopic radiofrequency ablation on the survival of patients with inoperable malignant biliary strictures: A large cohort study.

BACKGROUND AND AIMS: Endoscopic radiofrequency ablation (RFA) is an emerging technique for the palliation of inoperable malignant biliary strictures (MBSs). We aimed to systemically investigate the long-term outcome of RFA in a large cohort of patients. METHODS: We recruited 883 patients with various MBSs who underwent endoscopic interventions at two large-volume centers; 124 patients underwent RFA and stenting, whereas 759 underwent stenting alone. To overcome selection bias, we performed 1:4 propensity score matching (PSM). The main outcome was overall survival (OS). RESULTS: Following PSM, patients in the RFA group showed significantly longer OS (9.5 months; 95% CI: 7.7-11.3 months) than those in the stenting alone group (6.1 months; 95% CI: 5.6-6.6 months; P < .001). In stratified analyses, the improved OS was only demonstrated in the subgroup of extrahepatic cholangiocarcinoma (11.3 months 95% CI: 10.2-12.4 vs 6.9 months 95% CI: 6.0-7.8; P < .001), but not in the subgroups of gallbladder cancer, hepatocellular carcinoma, intrahepatic cholangiocarcinoma, pancreatic cancer, and other metastatic cancers (all P > .05). The survival benefits were noted only in the patients with non-metastatic cholangiocarcinoma (11.5 vs 7.4 months, P < .001). CONCLUSIONS: The survival benefits of endoscopic RFA appear to be limited to patients with extrahepatic cholangiocarcinoma without distant metastasis.

Endoscopic radiofrequency ablation may improve overall survival in patients with inoperable ampullary carcinoma.

OBJECTIVES: Patients with advanced ampullary carcinoma (AC) who are unsuitable for surgery are most likely to have poor outcomes. The role of endoscopic radiofrequency ablation (RFA) in this population has not been fully defined. We aimed to assess the short- and long-term outcomes of RFA in a large cohort of AC patients. METHODS: In this retrospective study, data of consecutive patients with pathologically proven AC who underwent successful endobiliary RFA and/or stent placement were collected. All patients did not undergo surgical resection. The primary outcome was overall survival (OS). The secondary outcomes included clinical success and adverse events. RESULTS: A total of 85 patients, 50 in the RFA plus stenting group and 35 in the stenting alone group, were identified. The median OS was significantly longer in the RFA group than in the stenting alone group (16.9 vs. 9.8 months, P < 0.001). In multivariable Cox analysis, RFA (hazards ratio 0.408; 95% confidence interval 0.235-0.706; P = 0.001) was the only independent OS predictor. Eight patients with stage II tumors, exclusively from the RFA group, survived for more than 3 years. Clinical success was comparable between the two groups (96% vs. 100%, P = 0.231). Early adverse events between the two groups were similar (10% vs. 2.9%, P = 0.206); however, late biliary/pancreatic stenoses occurred in three RFA patients who were successfully managed with endoscopic interventions. CONCLUSIONS: Endoscopic RFA appears to prolong patients' survival with acceptable safety; it may therefore be a feasible treatment option for patients with inoperable ampullary cancers.

Endoscopic radiofrequency ablation plus plastic stent placement versus stent placement alone for unresectable extrahepatic biliary cancer: a multicenter randomized controlled trial.

BACKGROUND AND AIMS: We sought to compare the efficacy and safety between endoscopic radiofrequency ablation (RFA) and stent placement alone in patients with unresectable extrahepatic biliary cancer (EBC). METHODS: In this randomized controlled trial, patients with locally advanced or metastatic cholangiocarcinoma (CCA) or ampullary cancer who were unsuitable for surgery were recruited from 3 tertiary centers. Eligible patients were randomly assigned to RFA plus plastic stent placement (RFA group) or plastic stent placement alone (stent placement alone group) in a 1:1 ratio. Both groups underwent 2 scheduled interventions with an interval of approximately 3 months. The primary outcome was overall survival (OS). RESULTS: Altogether, 174 participants completed the 2 index endoscopic interventions. No significant differences in baseline characteristics were noted between the 2 groups. The median OS was significantly higher in the RFA group (14.3 vs 9.2 months; hazard ratio, .488; 95% confidence interval, .351-.678; P < .001). A survival benefit was also shown in patients with CCA (13.3 vs 9.2 months; hazard ratio, .546; 95% confidence interval, .386-.771; P < .001). However, no significant between-group differences were found in jaundice control or stent patency duration. The postprocedural Karnofsky performance scores were significantly higher in the RFA group until 9 months (all P < .001). Adverse events were comparable between the 2 groups (27.6% vs 19.5%, P = .211), except for acute cholecystitis, which was more frequently observed in the RFA group (9 vs 0, P = .003). CONCLUSIONS: Compared with stent placement alone, additional RFA may improve OS and quality of life of patients with inoperable primary EBC who do not undergo systemic treatments. (Clinical trial registration number: NCT01844245.).

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.

Influence of fully covered metal stenting on the risk of post-endoscopic retrograde cholangiopancreatography pancreatitis: A large multicenter study·.

BACKGROUND AND AIM: Fully covered self-expandable metal stents (FCSEMSs) have been increasingly used in the management of benign or malignant biliary disorders. However, the risk of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) with transpapillary placement of the FCSEMS remains controversial. This study therefore aimed to investigate the risk of PEP in patients who received FCSEMS implantation. METHODS: In total, 602 patients who underwent endoscopic transpapillary FCSEMS placement at five Chinese medical centers, between 2011 and 2018, were included in this retrospective study. Patients who were younger than 18 years and with stent placement above the papilla were excluded from the study. PEP and the risk factors were reviewed. RESULTS: PEP occurred in 56 (9.3%) patients, and eight (1.3%) of them experienced moderate-to-severe PEP. The incidence of PEP rose to 14.6% (51/349) when patients had no pancreatic duct (PD) dilation, and even to 18.6% if no prophylactic approaches were adopted. Prophylactic PD stenting showed better efficacy in reducing the incidence of PEP than did rectal use of indomethacin (3.5% vs 10.8%, P = 0.023). Multivariate logistic regression revealed that difficult cannulation (OR 2.837, 95% CI 1.245-6.465, P = 0.013), PD dilation (OR 0.145, 95% CI 0.05-0.422, P < 0.001), and PD stenting (OR 0.247, 95% CI 0.089-0.686, P = 0.007) were significantly associated with PEP risk. Post-procedure cholecystitis was found in 4.0% of patients. CONCLUSION: The risk of post-procedure pancreatitis is modestly increased in patients receiving transpapillary FCSEMS placement, particularly when there is absence of PD dilation. Thus, prophylactic pancreatic stenting is recommended in such a condition.

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.

Initial Experience of ERCP-Guided Radiofrequency Ablation as the Primary Therapy for Inoperable Ampullary Carcinomas.

BACKGROUND: Endoscopic ablation of duodenal ampullary malignancy has not been fully assessed. AIMS: The study aimed to evaluate the efficacy and safety of Endoscopic retrograde cholangiopancreatograpy (ERCP)-guided radiofrequency ablation (RFA) for inoperable ampullary cancer. METHODS: Patients with inoperable ampullary cancer underwent ERCP-guided RFA from January 2012 to August 2017. RF energy (7-10 W) was delivered using bipolar RFA electrodes under endoscopic guidance. RFAs were repeated every 1-3 months until visible tumor was eliminated. All patients were followed up till June 2018, during which any biliary event was noted and managed endoscopically. RESULTS: Twenty-three patients underwent a median of two RFA sessions (range 1-6) at a median interval of 56 (range 35-90) days. Among 18 (78.3%) patients who received endoscopic re-evaluations, nine patients showed no remaining lesion and nine showed more than 50% tumor size reduction. During a median follow-up duration of 517 days (range 60-1836 days), eight (34.8%) patients required endoscopic re-interventions. The re-intervention rate at 6 months after RFA was 36.8%. Twelve patients were alive, among whom six required no biliary stenting. The accumulative mean survival was 1081 (95% CI 757.8-1404.0) days. RFA-related adverse events occurred in four cases (7.7%) including mild pancreatitis (1), bleeding (1), and late distal biliary stenosis (2). CONCLUSION: This pilot study shows that ERCP-guided RFA is safe to use and able to reduce tumor volume and re-interventions in patients with inoperable ampullary cancer.

The risk of acute cholangitis after endoscopic stenting for malignant hilar strictures: A large comprehensive study.

BACKGROUND AND AIM: Endoscopic stenting for unresectable malignant hilar biliary strictures (MHBS) remains challenging. Post-endoscopic retrograde cholangiopancreatography cholangitis (PEC) can be the most common and fatal adverse event. In the present study, we aimed to systematically evaluate the incidence, severity, risk factors, and consequences of PEC after endoscopic procedures for advanced MHBS. METHODS: Of 924 patients, we identified 502 patients with MHBS (Bismuth types II to IV) who underwent endoscopic stenting as the primary therapy at two centers over 16 years. PEC and its severity were verified according to the current Tokyo guidelines. RESULTS: A total of 108 patients (21.5%) experienced acute PEC. Mild, moderate, and severe cholangitis were encountered in 51 (10.1%), 42 (8.4%), and 15 (3.0%) patients, respectively. Multivariate analyses showed that metal stenting (verse plastic stenting) (OR 0.328, 95% CI 0.200-0.535, P < 0.001) and Bismuth classification (IV vs III/II) (OR 2.499, 95% CI 1.150-5.430) were independent predictors for PEC and the moderate/severe type. Patients with PEC had significantly lower clinical success rates (86.3% vs 41.7%, P < 0.001), a higher rate of early death (6.5% vs 0.5%, P < 0.001), a shorter median stent patency (4.9 vs 6.4 months, P < 0.001), and shorter overall survival (2.6 vs 5.2 months, P < 0.001) compared with the noncholangitis group. CONCLUSIONS: After endoscopic stenting for advanced MHBS, cholangitis may occur in as many as 21.5% of patients, which may be associated with a poor prognosis. The risk is high in patients with Bismuth type IV and may be reduced by using metal stents.

Author Correction: Toxicity evaluation of Wanzhou watershed of Yangtze Three Gorges Reservoir in the flood season in Caenorhabditis elegans.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Author Correction: Biosafety assessment of water samples from Wanzhou watershed of Yangtze Three Gorges Reservoir in the quiet season in Caenorhabditis elegans.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.