Indomethacin with or without prophylactic pancreatic stent placement to prevent pancreatitis after ERCP: a randomised non-inferiority trial.

BACKGROUND: The combination of rectally administered indomethacin and placement of a prophylactic pancreatic stent is recommended to prevent pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk patients. Preliminary evidence suggests that the use of indomethacin might eliminate or substantially reduce the need for stent placement, a technically complex, costly, and potentially harmful intervention. METHODS: In this randomised, non-inferiority trial conducted at 20 referral centres in the USA and Canada, patients (aged ≥18 years) at high risk for post-ERCP pancreatitis were randomly assigned (1:1) to receive rectal indomethacin alone or the combination of indomethacin plus a prophylactic pancreatic stent. Patients, treating clinicians, and outcomes assessors were masked to study group assignment. The primary outcome was post-ERCP pancreatitis. To declare non-inferiority, the upper bound of the two-sided 95% CI for the difference in post-ERCP pancreatitis (indomethacin alone minus indomethacin plus stent) would have to be less than 5% (non-inferiority margin) in both the intention-to-treat and per-protocol populations. This trial is registered with ClinicalTrials.gov (NCT02476279), and is complete. FINDINGS: Between Sept 17, 2015, and Jan 25, 2023, a total of 1950 patients were randomly assigned. Post-ERCP pancreatitis occurred in 145 (14·9%) of 975 patients in the indomethacin alone group and in 110 (11·3%) of 975 in the indomethacin plus stent group (risk difference 3·6%; 95% CI 0·6-6·6; p=0·18 for non-inferiority). A post-hoc intention-to-treat analysis of the risk difference between groups showed that indomethacin alone was inferior to the combination of indomethacin plus prophylactic stent (p=0·011). The relative benefit of stent placement was generally consistent across study subgroups but appeared more prominent among patients at highest risk for pancreatitis. Safety outcomes (serious adverse events, intensive care unit admission, and hospital length of stay) did not differ between groups. INTERPRETATION: For preventing post-ERCP pancreatitis in high-risk patients, a strategy of indomethacin alone was not as effective as a strategy of indomethacin plus prophylactic pancreatic stent placement. These results support prophylactic pancreatic stent placement in addition to rectal indomethacin administration in high-risk patients, in accordance with clinical practice guidelines. FUNDING: US National Institutes of Health.

Technical Factors Associated With the Benefit of Prophylactic Pancreatic Stent Placement During High-Risk Endoscopic Retrograde Cholangiopancreatography: A Secondary Analysis of the SVI Trial Data Set.

INTRODUCTION: Prophylactic pancreatic stent placement (PSP) is effective for preventing pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk cases, but the optimal technical approach to this intervention remains uncertain. METHODS: In this secondary analysis of 787 clinical trial patients who underwent successful stent placement, we studied the impact of (i) whether pancreatic wire access was achieved for the sole purpose of PSP or naturally during the conduct of the case, (ii) the amount of effort expended on PSP, (iii) stent length, (iv) stent diameter, and (v) guidewire caliber. We used logistic regression models to examine the adjusted association between each technical factor and post-ERCP pancreatitis (PEP). RESULTS: Ninety-one of the 787 patients experienced PEP. There was no clear association between PEP and whether pancreatic wire access was achieved for the sole purpose of PSP (vs occurring naturally; odds ratio [OR] 0.82, 95% confidence interval [CI] 0.37-1.84), whether substantial effort expended on stent placement (vs nonsubstantial effort; OR 1.58, 95% CI 0.73-3.45), stent length (>5 vs ≤5 cm; OR 1.01, 95% CI 0.63-1.61), stent diameter (≥5 vs <5 Fr; OR 1.13, 95% CI 0.65-1.96), or guidewire caliber (0.035 vs 0.025 in; 0.83, 95% CI 0.49-1.41). DISCUSSION: The 5 modifiable technical factors studied in this secondary analysis of large-scale randomized trial data did not appear to have a strong impact on the benefit of prophylactic PSP in preventing PEP after high-risk ERCP. Within the limitations of post hoc subgroup analysis, these findings may have important implications in procedural decision making and suggest that the benefit of PSP is robust to variations in technical approach.

The Impact of Difficult Biliary Cannulation on Post-ERCP Pancreatitis: A Secondary Analysis of the Stent versus Indomethacin Trial Dataset.

BACKGROUND AND AIMS: Difficult biliary cannulation (DBC) is a known risk factor for developing post-ERCP pancreatitis (PEP). To better understand how DBC increases PEP risk, we examined the interplay between technical aspects of DBC and known PEP risk factors. METHODS: This was a secondary analysis of a multicenter, randomized controlled trial comparing rectal indomethacin alone with the combination of rectal indomethacin and prophylactic pancreatic duct (PD) stent placement for PEP prophylaxis in high-risk patients. Participants were categorized into 3 groups: 1) DBC with high pre-procedure risk for PEP, 2) DBC without high pre-procedure risk, and 3) non-DBC at high pre-procedure risk. RESULTS: In all, 1601 (84.1%) participants experienced DBC, which required a mean of 12 (SD 10) cannulation attempts and mean duration of 14.7 minutes (SD 14.9). PEP rate was highest (20.7%) in DBC with high pre-procedure risk, followed by non-DBC with high pre-procedure risk (13.5%) and then DBC without high pre-procedure risk (8.8%). Increasing number of PD-wire passages (aOR:1.97, 95% CI:1.25-3.1) was associated with PEP in DBC, but PD injection, pancreatic sphincterotomy and number of cannulation attempts were not associated with PEP. Combining indomethacin with PD stenting lowered PEP risk (aOR:0.61, 95% CI:0.44-0.84) in DBCs. This protective effect was evident in up to at least 4 PD wire passages. CONCLUSIONS: DBC confers higher PEP risk in additive fashion to pre-procedural risk factors. PD wire passages appear to add the greatest PEP risk in DBCs, but combining indomethacin with PD stenting reduces this risk, even with increasing PD wire passages.

Treatment of walled-off necrosis using lumen-apposing metal stents versus plastic stents: a systematic review and meta-analysis of data from randomized trials.

BACKGROUND: Walled-off necrosis (WON) is highly morbid disease most effectively managed by endoscopic drainage with lumen-apposing metal stents (LAMSs) or plastic stents, with or without necrosectomy. This meta-analysis compared the clinical outcomes of patients included in randomized trials treated using LAMSs or plastic stents. METHODS: The MEDLINE and EMBASE databases were searched to identify all data collected from randomized trials comparing LAMSs and plastic stents for the treatment of WON. The primary outcome measure was need for endoscopic necrosectomy. RESULTS: Three studies comprising 206 patients met inclusion criteria. Except for procedure duration, which was significantly shorter for LAMSs (standardized mean difference [SMD] -1.22, 95%CI -1.64 to -0.79), there was no significant difference in need for necrosectomy (38.5% vs. 41.2%; risk ratio [RR] 1.07, 95%CI 0.79-1.45), number of interventions (SMD -0.09, 95%CI -0.40 to 0.22), treatment success (90.7% vs. 94.5%; RR 0.96, 95%CI 0.87-1.06), recurrence (4.6% vs. 0.6%; RR 3.73, 95%CI 0.42-33.0), readmission (42.6% vs. 50.2%; RR 0.84, 95%CI 0.62-1.14), length of hospitalization (SMD -0.06, 95%CI -0.55 to 0.43), mortality (8.5% vs. 9.8%; RR 0.70, 95%CI 0.30-1.66), new-onset organ failure (10.6% vs. 14.6%; RR 0.72, 95%CI 0.16-3.32), bleeding (11.0% vs. 10.7%; RR 1.09, 95%CI 0.34-3.44), procedural adverse events (23.6% vs. 19.2%; RR 1.38, 95%CI 0.82-2.33), or overall costs (SMD -0.04, 95%CI -0.31 to 0.24) between LAMSs and plastic stents, respectively. CONCLUSIONS: Except for procedure duration, there is no significant difference in clinical outcomes for patients with WON treated using LAMSs or plastic stents.

Impact of endoprosthesis type on inflammatory response in patients undergoing endoscopic drainage of pancreatic fluid collections.

OBJECTIVE: To study the impact of endoprosthesis type on inflammatory response in patients undergoing endoscopic ultrasound (EUS)-guided drainage of pancreatic fluid collections (PFC). METHODS: Patients undergoing EUS-guided PFC drainage and treated using lumen-apposing metal stents (LAMS) or plastic endoprostheses constituted the study cohort. The primary outcome was the presence of systemic inflammatory response syndrome (SIRS) after index intervention. Secondary outcomes were persistent organ failure, new onset organ failure, duration of hospitalization, and treatment success. RESULTS: In all, 303 patients were treated using LAMS (n = 247) or plastic stents (n = 56). At 48 h postintervention, the presence of SIRS (25.0 vs. 14.2%, P = 0.047), new onset SIRS (10.0 vs. 1.8%, P = 0.017), and new organ failure (5.4 vs. 0.4%, P = 0.003) were significantly higher in the plastic stent cohort compared to LAMS. On multivariable logistic regression analysis, the use of plastic stents (odds ratio [OR] 2.7, 95% confidence interval [CI] 1.2-6.0, P = 0.014), patients receiving high-acuity care (OR 5.1, 95% CI 2.5-10.4, P < 0.001) and the presence of ≥33% of necrosis (OR 4.5, 95% CI 2.0-10.0, P < 0.001) were significantly associated with the presence of SIRS or new organ failure. While there was no significant difference in treatment success (96.4 vs. 95.5%, P = 0.77), duration of hospitalization was significantly longer for the plastic stent cohort (mean [standard deviation] 12.5 [17.8] vs. 7.9 [10.1] days, P = 0.009). CONCLUSIONS: Use of plastic stents as compared to LAMS was associated with a higher proportion of SIRS and new organ failure that prolonged hospital stay. Therefore, placement of LAMS is recommended in sick patients and those with ≥33% necrosis to minimize inflammatory response.

Classical monocyte-derived macrophages as therapeutic targets of umbilical cord mesenchymal stem cells: comparison of intratracheal and intravenous administration in a mouse model of pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease that has no cure. Although mesenchymal stem cells (MSCs) have been reported to ameliorate lung inflammation and fibrosis in mouse models, their mechanisms of action remain unknown. Therefore, we aimed to determine the changes in various immune cells, especially macrophages and monocytes, involved in the effects of MSC treatment on pulmonary fibrosis. METHODS: We collected and analyzed explanted lung tissues and blood from patients with IPF who underwent lung transplantation. After establishing a pulmonary fibrosis model via the intratracheal administration of bleomycin (BLM) to 8-week-old mice, MSCs derived from human umbilical cords were administered intravenously or intratracheally on day 10 and the lungs were immunologically analyzed on days 14 and 21. Flow cytometry was performed to analyze the immune cell characteristics, and gene expression levels were examined using quantitative reverse transcription-polymerase chain reaction. RESULTS: In the histological analysis of explanted human lung tissues, the terminally fibrotic areas contained a larger number of macrophages and monocytes than the early fibrotic areas of the lungs. When human monocyte-derived macrophages (MoMs) were stimulated with interleukin-13 in vitro, the expression of type 2 macrophage (M2) markers was more prominent in MoMs from the classical monocyte subset than in those from intermediate or non-classical monocyte subsets, and MSCs suppressed M2 marker expression independent of MoM subsets. In the mouse model, the increased number of inflammatory cells in the bronchoalveolar lavage fluid and the degree of lung fibrosis observed in BLM-treated mice were significantly reduced by MSC treatment, which tended to be more prominent with intravenous administration than intratracheal administration. Both M1 and M2 MoMs were upregulated in BLM-treated mice. The M2c subset of M2 MoMs was significantly reduced by MSC treatment. Among M2 MoMs, M2 MoMs derived from Ly6C+ monocytes were most effectively regulated by the intravenous administration, not intratracheal administration, of MSCs. CONCLUSIONS: Inflammatory classical monocytes may play a role in lung fibrosis in human IPF and BLM-induced pulmonary fibrosis. Intravenous rather than intratracheal administration of MSCs may ameliorate pulmonary fibrosis by inhibiting monocyte differentiation into M2 macrophages.

Impact of Slim Linear Echoendoscope on the Practice of EUS.

BACKGROUND: Standard linear echoendoscopes have a large distal tip and bending radius, which can preclude adequate examination in some patients. OBJECTIVE: We examined the impact of having available slim linear echoendoscopes (SLE) on our endoscopic ultrasound (EUS) practice. MATERIALS AND METHODS: As a quality improvement measure, data on the need for the use of SLE were documented in 2000 consecutive procedures performed over a 10-month period from February to November 2022. When examination using a standard size echoendoscope failed due to technical limitations, the procedure was reattempted in the same session using a SLE. The main outcome was the impact of SLE, which was defined as the establishment of a new diagnosis or if findings altered treatment plan. RESULTS: A complete EUS examination failed in 23 of 2000 procedures (1.15%, 95% CI, 0.73-1.72%) performed using standard size echoendoscope (14 male, median age 73 y [IQR 66 to 79]). The examination was technically successful when using SLE in 22 of 23 (95.6%) patients. SLE impacted clinical management in all 22 patients (100%) by establishing tissue diagnosis in 19 and/or altering subsequent treatment plan in 5. Adverse event of transient hypoxia was observed in one patient (4.3%). CONCLUSIONS: A very experienced EUS team required SLE in 1.1% of consecutive examinations. Our findings suggest that when used, 95% of patients benefitted as it had a significant impact on their clinical management.

Orlando Protocol for single session ductal clearance of common bile duct stones at endosopic retrograde cholangiopancreatography.

OBJECTIVES: Approach to management of common bile duct stones (CBDS) by endoscopic retrograde cholangiopancreatography (ERCP) is not standardized. We examined outcomes by applying predetermined protocol for CBDS management. METHODS: When standard extraction techniques failed at ERCP, presence of tapered bile duct and stone-duct ratio were calculated. Large balloon sphincteroplasty (LBS) and/or mechanical/single-operator cholangioscopy-guided lithotripsy was performed based on presence of tapered bile duct and stone-duct mismatch. Primary outcome was single-session ductal clearance. Secondary outcome was adverse events. RESULTS: Of 409 patients treated over 16 months, 321 (78.5%) had no tapered bile duct or stone-duct mismatch, and single-session ductal clearance was achieved using standard techniques in 99.7% over median duration of 14 min (interquartile range [IQR] 9-21 min). Of 88 (21.5%) patients with difficult CBDS, tapered duct was seen in 79 (89.8%) and/or stone-duct mismatch in 36 (40.9%). Single-session ductal clearance was achieved in all 88 patients (100%) by LBS in 79 (89.8%), mechanical lithotripsy in 20 (22.7%), and single-operator cholangioscopy-guided lithotripsy in 16 (18.2%) over a median duration of 29 min (IQR 17-47 min). Overall, single-session ductal clearance was achieved in 99.8% with adverse events in 17 (4.2%) that included perforation in two, postsphincterotomy bleeding in one, and mild/moderate post-ERCP pancreatitis in 14 patients. CONCLUSIONS: A predetermined protocol optimized outcomes by enabling single-session ductal clearance of CBDS with high technical success and low adverse events.

Effect of Acinetobacter lwoffii on the modulation of macrophage activation and asthmatic inflammation.

BACKGROUND: Although lung macrophages are directly exposed to external stimuli, their exact immunologic roles in asthma are still largely unknown. The aim of this study was to investigate the anti-asthmatic effect of Acinetobacter lwoffii in terms of lung macrophage modulation. METHODS: Six-week-old female BALB/c mice were sensitized and challenged with ovalbumin (OVA) with or without intranasal administration of A. lwoffii during the sensitization period. Airway hyperresponsiveness and inflammation were evaluated. Using flow cytometry, macrophages were subclassified according to their activation status. In the in vitro study, a murine alveolar macrophage cell line (MH-S) treated with or without A. lwoffii before IL-13 stimulation were analysed by quantitative RT-PCR. RESULTS: In a murine asthma model, the number of inflammatory cells, including macrophages and eosinophils, decreased in mice treated with A. lwoffii (A. lwoffii/OVA group) compared with untreated mice (OVA group). The enhanced expression of MHCII in macrophages in the OVA group was decreased by A. lwoffii treatment. M2 macrophage subtypes were significantly altered. A. lwoffii treatment decreased CD11b+ M2a and CD11b+ M2c macrophages, which showed strong positive correlations with Th2 cells, ILC2 and eosinophils. In contrast, CD11b+ M2b macrophages were significantly increased by A. lwoffii treatment and showed strong positive correlations with ILC1 and ILC3. In vitro, A. lwoffii down-regulated the expression of M2 markers related but up-regulated those related to M2b macrophages. CONCLUSIONS AND CLINICAL RELEVANCE: Intranasal A. lwoffii exposure suppresses asthma development by suppressing the type 2 response via modulating lung macrophage activation, shifting M2a and M2c macrophages to M2b macrophages.

Peripheral blood transcriptomic clusters uncovered immune phenotypes of asthma.

BACKGROUND: Transcriptomic analysis has been used to elucidate the complex pathogenesis of heterogeneous disease and may also contribute to identify potential therapeutic targets by delineating the hub genes. This study aimed to investigate whether blood transcriptomic clustering can distinguish clinical and immune phenotypes of asthmatics, and microbiome in asthmatics. METHODS: Transcriptomic expression of peripheral blood mononuclear cells (PBMCs) from 47 asthmatics and 21 non-asthmatics was measured using RNA sequencing. A hierarchical clustering algorithm was used to classify asthmatics. Differentially expressed genes, clinical phenotypes, immune phenotypes, and microbiome of each transcriptomic cluster were assessed. RESULTS: In asthmatics, three distinct transcriptomic clusters with numerously different transcriptomic expressions were identified. The proportion of severe asthmatics was highest in cluster 3 as 73.3%, followed by cluster 2 (45.5%) and cluster 1 (28.6%). While cluster 1 represented clinically non-severe T2 asthma, cluster 3 tended to include severe non-T2 asthma. Cluster 2 had features of both T2 and non-T2 asthmatics characterized by the highest serum IgE level and neutrophil-dominant sputum cell population. Compared to non-asthmatics, cluster 1 showed higher CCL23 and IL1RL1 expression while the expression of TREML4 was suppressed in cluster 3. CTSD and ALDH2 showed a significant positive linear relationship across three clusters in the order of cluster 1 to 3. No significant differences in the diversities of lung and gut microbiomes were observed among transcriptomic clusters of asthmatics and non-asthmatics. However, our study has limitations in that small sample size data were analyzed with unmeasured confounding factors and causal relationships or function pathways were not verified. CONCLUSIONS: Genetic clustering based on the blood transcriptome may provide novel immunological insight, which can be biomarkers of asthma immune phenotypes. Trial registration Retrospectively registered.

Endoscopic biliary drainage for malignant distal biliary obstruction: Which is better - endoscopic retrograde cholangiopancreatography or endoscopic ultrasound?

Presently, following endoscopic ultrasound (EUS)-guided biopsy, an endoscopic retrograde cholangiopancreatography (ERCP) with transpapillary stenting is performed for palliation of malignant distal biliary obstruction (MDBO). However, technical failure and postprocedure pancreatitis are limitations to ERCP. Endoscopic ultrasonography-guided biliary drainage (EUS-BD) after a failed ERCP has a 90% technical success rate and has been shown to be superior when compared to percutaneous methods, making EUS an increasingly recognized option for biliary drainage. Supporting this approach, findings from recently concluded randomized trials suggest that the safety profile and technical outcomes for EUS-BD are comparable or even superior to that of ERCP for primary biliary decompression in patients with MDBO. Also, EUS-BD is increasingly being utilized in patients with altered surgical anatomy in lieu of percutaneous techniques and balloon-assisted enteroscopy. A growing body of evidence supports the notion that, in the future, EUS may become the primary modality by which biliary decompression is undertaken in the majority of patients with MDBO. The roadmap to this eventuality may require further optimization of procedural techniques, technological innovations, and cost reduction.

Validation of the Orlando Protocol for endoscopic management of pancreatic fluid collections in the era of lumen-apposing metal stents.

OBJECTIVES: Although lumen-apposing metal stents (LAMS) are being increasingly used in lieu of plastic stents, the clinical approach to endoscopic management of pancreatic fluid collections (PFCs) is poorly standardized. We compared outcomes of approaches over two time intervals, initially using plastic stents and later integrating LAMS. METHODS: This was a retrospective, observational, before-after study of prospectively collected data on consecutive patients with symptomatic PFCs managed over two time periods. In the initial period (January 2010-January 2015) endoscopic treatment was undertaken with plastic stents and in the later period (February 2015-August 2020) by integration of LAMS with selective use of plastic stents. The treatment strategy in both periods were tailored to size, extent, type of PFC and stepwise response to intervention. The main outcome was treatment success, defined as resolution of PFC and presenting symptoms at 6-month follow-up. RESULTS: A total of 160 patients were treated with plastic stents and 227 patients were treated using an integrated LAMS approach. Treatment success was significantly higher for the integrated approach compared to using only plastic stents (95.6 vs. 89.4%; P = 0.018), which was confirmed to be predictive of treatment success on multivariable logistic regression analysis (odds ratio 2.7, 95% confidence interval 1.1-6.4; P = 0.028). CONCLUSIONS: A structured approach integrating LAMS with selective use of plastic stents improved treatment success in patients with PFCs compared to an approach using only plastic stents.

Equivalent performance of single-use and reusable duodenoscopes in a randomised trial.

OBJECTIVE: Single-use duodenoscopes have been recently developed to eliminate risk of infection transmission from contaminated reusable duodenoscopes. We compared performances of single-use and reusable duodenoscopes in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). DESIGN: Patients with native papilla requiring ERCP were randomised to single-use or reusable duodenoscope. Primary outcome was comparing number of attempts to achieve successful cannulation of desired duct. Secondary outcomes were technical performance that measured duodenoscope manoeuvrability, mechanical-imaging characteristics and ability to perform therapeutic interventions, need for advanced cannulation techniques or cross-over to alternate duodenoscope group to achieve ductal access and adverse events. RESULTS: 98 patients were treated using single-use (n=48) or reusable (n=50) duodenoscopes with >80% graded as low-complexity procedures. While median number of attempts to achieve successful cannulation was significantly lower for single-use cohort (2 vs 5, p=0.013), ease of passage into stomach (p=0.047), image quality (p<0.001), image stability (p<0.001) and air-water button functionality (p<0.001) were significantly worse. There was no significant difference in rate of cannulation, adverse events including mortality (one patient in each group), need to cross-over or need for advanced cannulation techniques to achieve ductal access, between cohorts. On multivariate logistic regression analysis, only duodenoscope type (single-use) was associated with less than six attempts to achieve selective cannulation (p=0.012), when adjusted for patient demographics, procedural complexity and type of intervention. CONCLUSION: Given the overall safety profile and similar technical performance, single-use duodenoscopes represent an alternative to reusable duodenoscopes for performing low-complexity ERCP procedures in experienced hands. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov number: NCT04143698.

Importance of Disconnected Pancreatic Duct Syndrome in Recurrence of Pancreatic Fluid Collections Initially Drained Using Lumen-Apposing Metal Stents.

BACKGROUND & AIMS: Indwelling plastic endoprosthesis in patients with disconnected pancreatic duct syndrome (DPDS) reduces the risk of pancreatic fluid collection (PFC) recurrence. Although lumen-apposing metal stents (LAMS) are used with increasing frequency for PFC drainage, they require timely removal and little is known about their effects in patients with DPDS and recurrence of PFC. METHODS: We performed a prospective study of patients who underwent endoscopic ultrasound-guided drainage of PFC using LAMS and were found to have DPDS. After resolution of PFC, LAMS were replaced with double-pigtail plastic stents. The primary outcome was to compare PFC recurrence between patients with DPDS who did vs did not receive replacements with plastic stents after removal of the LAMS. RESULTS: Of 188 PFC patients treated with LAMS, 94 had DPDS, 71 had intact pancreatic ducts, and duct patency was unknown in 23. In patients with DPDS, replacement of LAMS with plastic stents was successful in 70 patients (74.5%) and technically unsuccessful in 24 patients (25.5%). At a median follow up of 183 days (interquartile range, 179-188 days), although none of the patients with an intact duct had a recurrence of PFC, 7 of the 94 patients with DPDS had recurrence of PFC (7.4%) (P = .020). PFC recurred in 1 of 70 patients with DPDS in whom replacement of LAMS with plastic stent was successful (1.4%) and in 6 of 24 patients with unsuccessful stent replacement (25.0%) (P = .001). CONCLUSIONS: In treatment of PFCs with LAMS in patients with DPDS, it is important to replace the LAMS with indwelling plastic stents to minimize PFC recurrence and reduce morbidity. Clinicaltrials.gov no: NCT02422095.

Single-use duodenoscopes: where are we and where are we going?

PURPOSE OF REVIEW: Given the growing concerns about infection transmission from use of contaminated reusable duodenoscopes, technological advancements have been made that vary from modifications of existing designs to development of single-use devices. RECENT FINDINGS: To circumvent mechanical limitations that preclude access to critical areas of a duodenoscope to perform thorough cleaning and disinfection, single-use disposable duodenoscopes have been developed. A thorough assessment of this technology is limited by the minimal published data that is currently available. This opinion assesses the current technical functionality of these devices, potential for further improvements, implications for healthcare economics and the future of gastrointestinal endoscopy. SUMMARY: Currently available data suggest that majority of endoscopic retrograde cholangiopancreatography procedures can be safely performed using single-use duodenoscopes. The ability to improve technical functionality, incorporate futuristic technology and secure financial reimbursement from insurance carriers will largely define the future prospects of this recent innovation.

Outcomes of a Structured, Stepwise Approach to Endoscopic Necrosectomy.

BACKGROUND AND AIM: Despite the increasing number of procedures being performed, there is no consensus on the optimal approach to performing direct endoscopic necrosectomy (DEN), which is a labor-intensive, nonstandardized intervention. We prospectively validated the usefulness of a predefined, structured, stepwise approach to DEN with the objective of improving procedural efficiency and resource use. MATERIALS AND METHODS: A prospective study of patients with necrotizing pancreatitis who after endoscopic transluminal drainage did not have clinical improvement and required DEN. The study was undertaken in 2 phases. Phase I was a retrospective analysis of interventions performed using an unstructured, conventional approach. Median of 3 necrosectomy sessions (range, 2 to 3) were required to achieve 80% treatment success in 20 patients. On the basis of these observations, a structured approach that included 3 steps (debridement, necrosis extraction, and irrigation) was developed and validated prospectively in phase II in 39 patients. The main outcome was to compare procedural efficiency defined as a number of necrosectomy sessions to achieve treatment success. RESULTS: Although there was no significant difference in treatment success (phase I=80.0 vs. phase II=94.9%, P=0.17), the procedure was more efficient in phase II [median session, 2 (interquartile range=1 to 3) vs. 3 (interquartile range=2 to 3); P=0.003]. Multiple logistic regression analysis revealed that a structured, stepwise approach was associated with fewer necrosectomy sessions to achieve treatment success (odds ratio=4.7; 95% confidence interval=1.5-15.0; P=0.008) when adjusted for patient demographics, lab parameters, and disease characteristics. CONCLUSIONS: By decreasing the number of necrosectomy sessions, a structured, stepwise approach to endoscopic necrosectomy seems to improve procedural efficiency.

Prospective evaluation of an assessment tool for technical performance of duodenoscopes.

OBJECTIVE: While single-use and detachable-tip duodenoscopes have been recently developed to overcome risks of infection transmission, there are no reliable tools to objectively assess their technical performance. We evaluated the reliability and validity of a newly developed tool to assess the technical performance of reusable duodenoscopes. METHODS: An assessment tool was developed to measure duodenoscope performance based on three distinct criteria: maneuverability, mechanical/imaging characteristics and ability to perform requisite interventions. The assessment tool was tested prospectively on duodenoscopes used in endoscopic retrograde cholangiopancreatography (ERCP) procedures at nine academic medical centers over a 6-month period. The main outcome was reliability of the duodenoscope assessment tool, which was estimated using Cronbach's coefficient alpha (α). The secondary outcome was validity of the assessment tool. RESULTS: The assessment tool evaluated technical performance of reusable duodenoscopes in 1080 ERCP procedures. Indications were biliary in 92.8% and pancreatic in 7.2% procedures. The overall Cronbach's coefficient α for maneuverability was 0.81, assessment of mechanical/imaging characteristics was 0.92, and ability to perform requisite interventions was 0.87. On multiple linear regression analysis, prolonged procedure duration, older patient age and pancreatic interventions were significantly positively associated with higher (worse) scores. CONCLUSIONS: The newly developed assessment tool appears reliable and valid for evaluating the technical performance of duodenoscopes. Registration: ClinicalTrials.gov Identifier: NCT04004533.

Efficacy of Single-Operator Cholangioscopy-Guided Lithotripsy Compared With Large Balloon Sphincteroplasty in Management of Difficult Bile Duct Stones in a Randomized Trial.

BACKGROUND & AIMS: Although single-operator cholangioscopy (SOC)-guided lithotripsy and large balloon sphincteroplasty (LBS)-based techniques are effective rescue measures, the ideal approach to management of difficult bile duct stones is unclear. We conducted a randomized trial to compare the effectiveness of SOC-guided lithotripsy and LBS-based approaches for endoscopic management of difficult bile duct stones. METHODS: Patients with difficult bile duct stones who failed retrieval using balloon or basket were randomly assigned to groups that received SOC-guided laser lithotripsy (SOC-LL, n = 33) or LBS (n = 33), from June 2016 through August 2018. When assigned treatment was unsuccessful, patients underwent mechanical lithotripsy before crossing over to the other group. The main outcome was treatment success, defined as ability to clear the duct in 1 session. Secondary outcomes were adverse events and treatment costs. RESULTS: A higher proportion of patients in the SOC-LL group had treatment success (93.9%) than in the LBS group (72.7%; P = .021). On multiple logistic regression analysis, treatment success was significantly associated with use of SOC-LL (odds ratio [OR], 8.7; 95% CI, 1.3-59.3; P = .026), stone to extrahepatic bile duct ratio of 1 or less (OR, 28.8; 95% CI, 1.2-687.6; P = .038), and lack of a tapered bile duct (OR, 26.9; 95% CI, 1.3-558.2; P = .034). There was no significant difference between groups in adverse events (9.1% in the SOC-LL group vs 3.0% in the LBS group, P = .61) or overall treatment cost ($16,684 in the SOC-LL group vs $10,626 in the LBS group; P = .097). CONCLUSIONS: In a randomized trial of patients with difficult bile stones that cannot be cleared by standard maneuvers, SOC-guided lithotripsy leads to duct clearance in a significantly higher proportion of patients than LBS-particularly when stone size exceeds the diameter of the extrahepatic bile duct. Adjunct lithotripsy might be required in patients with tapered distal bile duct, because LBS alone is less likely to be successful. ClinicalTrials.gov no: NCT00852072.

Optimizing Outcomes of Single-Operator Cholangioscopy-Guided Biopsies Based on a Randomized Trial.

BACKGROUND & AIMS: Although single-operator cholangioscopy is considered to be the most sensitive method for tissue acquisition in patients with indeterminate bile duct strictures (IBDS), methods are needed to optimize the specimen collection and processing techniques. We aimed to determine the optimal method for specimen processing and identify the number of biopsies required to establish a definitive diagnosis. METHODS: Patients with IBDS were randomly assigned to groups that underwent specimen processing using the onsite (n = 32) or offsite (n = 30) method. The primary outcome was to compare operating characteristics of onsite vs offsite specimen processing techniques. The secondary outcome was number of biopsies needed to establish definitive diagnosis. A final diagnosis was established at surgery or after a minimum clinical follow-up period of 18 months RESULTS: The final diagnosis was benign disease in 33 patients and malignancy in 29 patients. There were no significant differences between the offsite and onsite groups in diagnostic accuracy (90% vs 87.5%; P=.99), sensitivity (76.9% vs 75%; P=.99), specificity (100% vs 100%; P=.99), positive predictive value (100% vs 100%; P=.99), or negative predictive value (85% vs 80%; P=.99). Although diagnoses were established by analysis of a median of 1 biopsy in the onsite cohort (interquartile range, 1-1.5), the diagnostic accuracy was identical (90%) in each group, regardless of whether 3 or 4 biopsies were collected from each patient in the offsite cohort. CONCLUSIONS: In a prospective comparative study, we found that centers without onsite cytopathology support that analyze 3 single-operator cholangioscopy-guided biopsies of a biliary stricture and process the specimens offsite make the correct diagnosis for 90% of cases. ClinicalTrials.gov, Number: NCT01815619.

An Endoscopic Transluminal Approach, Compared With Minimally Invasive Surgery, Reduces Complications and Costs for Patients With Necrotizing Pancreatitis.

BACKGROUND & AIMS: Infected necrotizing pancreatitis is a highly morbid disease with poor outcomes. Intervention strategies have progressed from open necrosectomy to minimally invasive approaches. We compared outcomes of minimally invasive surgery vs endoscopic approaches for patients with infected necrotizing pancreatitis. METHODS: We performed a single-center, randomized trial of 66 patients with confirmed or suspected infected necrotizing pancreatitis who required intervention from May 12, 2014, through March 24, 2017. Patients were randomly assigned to groups that received minimally invasive surgery (laparoscopic or video-assisted retroperitoneal debridement, depending on location of collection, n = 32) or an endoscopic step-up approach (transluminal drainage with or without necrosectomy, n = 34). The primary endpoint was a composite of major complications (new-onset multiple organ failure, new-onset systemic dysfunction, enteral or pancreatic-cutaneous fistula, bleeding and perforation of a visceral organ) or death during 6 months of follow-up. RESULTS: The primary endpoint occurred in 11.8% of patients who received the endoscopic procedure and 40.6% of patients who received the minimally invasive surgery (risk ratio 0.29; 95% confidence interval 0.11-0.80; P = .007). Although there was no significant difference in mortality (endoscopy 8.8% vs surgery 6.3%; P = .999), none of the patients assigned to the endoscopic approach developed enteral or pancreatic-cutaneous fistulae compared with 28.1% of the patients who underwent surgery (P = .001). The mean number of major complications per patient was significantly higher in the surgery group (0.69 ± 1.03) compared with the endoscopy group (0.15 ± 0.44) (P = .007). The physical health scores for quality of life at 3 months was better with the endoscopic approach (P = .039) and mean total cost was lower ($75,830) compared with $117,492 for surgery (P = .039). CONCLUSIONS: In a randomized trial of 66 patients, an endoscopic transluminal approach for infected necrotizing pancreatitis, compared with minimally invasive surgery, significantly reduced major complications, lowered costs, and increased quality of life. Clinicaltrials.gov no: NCT02084537.