Clinical trial protocol for PanDox: a phase I study of targeted chemotherapy delivery to non-resectable primary pancreatic tumours using thermosensitive liposomal doxorubicin (ThermoDox®) and focused ultrasound.

BACKGROUND: The dense stroma of pancreatic ductal adenocarcinomas is a major barrier to drug delivery. To increase the local drug diffusion gradient, high doses of chemotherapeutic agent doxorubicin can be released from thermally-sensitive liposomes (ThermoDox®) using ultrasound-mediated hyperthermia at the tumour target. PanDox is designed as a Phase 1 single centre study to investigate enhancing drug delivery to adult patients with non-operable pancreatic ductal adenocarcinomas. The study compares a single cycle of either conventional doxorubicin alone or ThermoDox® with focused ultrasound-induced hyperthermia for targeted drug release. METHODS: Adults with non-resectable pancreatic ductal adenocarcinoma are allocated to receive a single cycle of either doxorubicin alone (Arm A) or ThermoDox® with focused ultrasound-induced hyperthermia (Arm B), based on patient- and tumour-specific safety conditions. Participants in Arm B will undergo a general anaesthetic and pre-heating of the tumour by extra-corporal focused ultrasound (FUS). Rather than employing invasive thermometry, ultrasound parameters are derived from a patient-specific treatment planning model to reach the 41 °C target temperature for drug release. ThermoDox® is then concurrently infused with further ultrasound exposure. Tumour biopsies at the targeted site from all patients are analysed post-treatment using high performance liquid chromatography to quantify doxorubicin delivered to the tumour. The primary endpoint is defined as a statistically significant enhancement in concentration of total intra-tumoural doxorubicin, comparing samples from patients receiving liposomal drug with FUS to free drug alone. Participants are followed for 21 days post-treatment to assess secondary endpoints, including radiological assessment to measure changes in tumour activity by Positron Emission Tomography Response Criteria in Solid Tumours (PERCIST) criteria, adverse events and patient-reported symptoms. DISCUSSION: This early phase study builds on previous work targeting tumours in the liver to investigate whether enhancement of chemotherapy delivery using ultrasound-mediated hyperthermia can be translated to the stroma-dense environment of pancreatic ductal adenocarcinoma. If successful, it could herald a new approach towards managing these difficult-to-treat tumours. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04852367 . Registered 21st April 2022. EudraCT number: 2019-003950-10 (Registered 2019) Iras Project ID: 272253 (Registered 2019) Ethics Number: 20/EE/0284.

UK and Ireland Joint Advisory Group (JAG) consensus statements for training and certification in diagnostic endoscopic ultrasound (EUS).

BACKGROUND AND AIMS: International endoscopy societies vary in their approach for credentialing individuals in endoscopic ultrasound (EUS) to enable independent practice; however, there is no consensus in this or its implementation. In 2019, the Joint Advisory Group on GI Endoscopy (JAG) commissioned a working group to examine the evidence relating to this process for EUS. The aim of this was to develop evidence-based recommendations for EUS training and certification in the UK. METHODS: Under the oversight of the JAG quality assurance team, a modified Delphi process was conducted which included major stakeholders from the UK and Ireland. A formal literature review was made, initial questions for study were proposed and recommendations for training and certification in EUS were formulated after a rigorous assessment using the Grading of Recommendation Assessment, Development and Evaluation tool and subjected to electronic voting to identify accepted statements. These were peer reviewed by JAG and relevant stakeholder societies before consensus on the final EUS certification pathway was achieved. RESULTS: 39 initial questions were proposed of which 33 were deemed worthy of assessment and finally formed the key recommendations. The statements covered four key domains, such as: definition of competence (13 statements), acquisition of competence (10), assessment of competence (5) and postcertification mentorship (5). Key recommendations include: (1) minimum of 250 hands-on cases before an assessment for competency can be made, (2) attendance at the JAG basic EUS course, (3) completing a minimum of one formative direct observation of procedural skills (DOPS) every 10 cases to allow the learning curve in EUS training to be adequately studied, (4) competent performance in summative DOPS assessments and (5) a period of mentorship over a 12-month period is recommended as minimum to support and mentor new service providers. CONCLUSIONS: An evidence-based certification pathway has been commissioned by JAG to support and quality assure EUS training. This will form the basis to improve quality of training and safety standards in EUS in the UK and Ireland.

Impact of prior biliary stenting on diagnostic performance of endoscopic ultrasound for mesenteric vascular staging in patients with head of pancreas and periampullary malignancy.

OBJECTIVE: The diagnostic performance of endoscopic ultrasound (EUS) for stratification of head of pancreas and periampullary tumours into resectable, borderline resectable and locally advanced tumours is unclear as is the effect of endobiliary stents. The primary aim of the study was to assess the diagnostic performance of EUS for resectability according to stent status. DESIGN: A retrospective study was performed. All patients presenting with a solid head of pancreas mass who underwent EUS and surgery with curative intent during an 8-year period were included. Factors with possible impact on diagnostic performance of EUS were analysed using logistic regression. RESULTS: Ninety patients met inclusion criteria and formed the study group. A total of 49 (54%) patients had an indwelling biliary stent at the time of EUS, of which 36 were plastic and 13 were self-expanding metal stents (SEMS). Twenty patients underwent venous resection and reconstruction (VRR). Staging was successfully performed in 100% unstented cases, 97% plastic stent and 54% SEMS, p<0.0001. In successfully staged patients, sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) for classification of resectability were 70%, 70%, 70%, 42% and 88%. For vascular involvement (VI), sensitivity, specificity, accuracy, PPV and NPV were 80%, 68%, 69%, 26% and 96%. Increasing tumour size OR 0.53 (95% CI, 0.30 to 0.95) was associated with a decrease in accuracy of VI classification. CONCLUSIONS: EUS has modest diagnostic performance for stratification of staging. Staging was less likely to be completed when a SEMS was in situ. Staging EUS should ideally be performed before endoscopic retrograde cholangiopancreatography and biliary drainage.

Controversies in ERCP: Technical aspects.

The aim of the series of papers on controversies of biliopancreatic drainage procedures is to discuss pros and cons of the varying clinical practices and techniques in ERCP and EUS for drainage of biliary and pancreatic ducts. While the first part focuses on indications, clinical and imaging prerequisites prior to ERCP, sedation options, post-ERCP pancreatitis prophylaxis, and other related technical topics, the second part discusses specific procedural ERCP techniques including precut techniques and their timing as well as management algorithms. In addition, reviews on controversies in EUS-guided bile duct and pancreatic drainage procedures are under preparation.

Controversies in ERCP: Indications and preparation.

The aim of the series of papers on controversies of biliopancreatic drainage procedures is to discuss the pros and cons of the varying clinical practices and techniques in ERCP and EUS for drainage of biliary and pancreatic ducts. The first part focuses on indications, clinical and imaging prerequisites before ERCP, sedation options, post-ERCP pancreatitis (PEP) prophylaxis, and other related technical topics. In the second part, specific procedural ERCP-techniques including precut techniques and its timing as well as management algorithms are discussed. In addition, controversies in EUS-guided bile duct and pancreatic drainage procedures are under preparation.

Cell-free DNA TAPS provides multimodal information for early cancer detection.

Multimodal, genome-wide characterization of epigenetic and genetic information in circulating cell-free DNA (cfDNA) could enable more sensitive early cancer detection, but it is technologically challenging. Recently, we developed TET-assisted pyridine borane sequencing (TAPS), which is a mild, bisulfite-free method for base-resolution direct DNA methylation sequencing. Here, we optimized TAPS for cfDNA (cfTAPS) to provide high-quality and high-depth whole-genome cell-free methylomes. We applied cfTAPS to 85 cfDNA samples from patients with hepatocellular carcinoma (HCC) or pancreatic ductal adenocarcinoma (PDAC) and noncancer controls. From only 10 ng of cfDNA (1 to 3 ml of plasma), we generated the most comprehensive cfDNA methylome to date. We demonstrated that cfTAPS provides multimodal information about cfDNA characteristics, including DNA methylation, tissue of origin, and DNA fragmentation. Integrated analysis of these epigenetic and genetic features enables accurate identification of early HCC and PDAC.

Curriculum for ERCP and endoscopic ultrasound training in Europe: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement.

The European Society of Gastrointestinal Endoscopy (ESGE) has recognized the need to formalize and enhance training in endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS). This manuscript represents the outcome of a formal Delphi process resulting in an official Position Statement of the ESGE and provides a framework to develop and maintain skills in ERCP and EUS. This curriculum is set out in terms of the prerequisites prior to training; recommended steps of training to a defined syllabus; the quality of training; and how competence should be defined and evidenced before independent practice. 1: Trainees should be competent in gastroscopy prior to commencing training. Formal training courses and the use of simulation in training are recommended. 2: Trainees should keep a contemporaneous logbook of their procedures, including key performance indicators and the degree of independence. Structured formative assessment is encouraged to enhance feedback. There should be a summative assessment process prior to commencing independent practice to ensure there is robust evidence of competence. This evidence should include a review of a trainee's procedure volume and current performance measures. A period of mentoring is strongly recommended in the early stages of independent practice. 3: Specifically for ERCP, all trainees should be competent up to Schutz level 2 complexity (management of distal biliary strictures and stones > 10 mm), with advanced ERCP requiring a further period of training. Prior to independent practice, ESGE recommends that a trainee can evidence a procedure volume of > 300 cases, a native papilla cannulation rate of ≥ 80 % (90 % after a period of mentored independent practice), complete stones clearance of ≥ 85 %, and successful stenting of distal biliary strictures of ≥ 90 % (90 % and 95 % respectively after a mentored period of independent practice). 4: The progression of EUS training and competence attainment should start from diagnostic EUS and then proceed to basic therapeutic EUS, and finally to advanced therapeutic EUS. Before independent practice, ESGE recommends that a trainee can evidence a procedure volume of > 250 cases (75 fine-needle aspirations/biopsies [FNA/FNBs]), satisfactory visualization of key anatomical landmarks in ≥ 90 % of cases, and an FNA/FNB accuracy rate of ≥ 85 %. ESGE recognizes the often inadequate quality of the evidence and the need for further studies pertaining to training in advanced endoscopy, particularly in relation to therapeutic EUS.

Novel multidisciplinary hub-and-spoke tertiary service for the management of severe acute pancreatitis.

OBJECTIVE: Severe acute pancreatitis (SAP) is associated with high mortality (15%-30%). Current guidelines recommend these patients are best managed in a multidisciplinary team setting. This study reports experience in the management of SAP within the UK's first reported hub-and-spoke pancreatitis network. DESIGN: All patients with SAP referred to the remote care pancreatitis network between 2015 and 2017 were prospectively entered onto a database by a dedicated pancreatitis specialist nurse. Baseline characteristics, aetiology, intensive care unit (ICU) stay, interventions, complications, mortality and follow-up were analysed. RESULTS: 285 patients admitted with SAP to secondary care hospitals during the study period were discussed with the dedicated pancreatitis specialist nurse and referred to the regional service. 83/285 patients (29%; 37 male) were transferred to the specialist centre mainly for drainage of infected pancreatic fluid collections (PFC) in 95% (n=79) of patients. Among the patients transferred; 29 (35%) patients developed multiorgan failure with an inpatient mortality of 14% (n=12/83). The median follow-up was 18.2 months (IQR=11.25-35.51). Multivariate analysis showed that transferred patients had statistically significant longer overall hospital stay (p<0.001) but less ICU stay (p<0.012). CONCLUSION: This hub-and-spoke model facilitates the management of the majority of patients with SAP in secondary care setting. 29% warranted transfer to our tertiary centre, predominantly for endoscopic drainage of PFCs. An evidence-based approach with a low threshold for transfer to tertiary care centre can result in lower mortality for SAP and fewer days in ICU.

Motion training on a validated mechanical ERCP simulator improves novice endoscopist performance of selective cannulation: a multicenter trial.

Background and study aims Current data show that traditional training methods in endoscopic retrograde cholangiopancreatography (ERCP) fall short of producing competent trainees. We aimed to evaluate whether a novel approach to simulator-based training might improve the learning curve for novice endoscopists training in ERCP. Methods We conducted a multicenter, randomized controlled trial using a validated mechanical simulator (the Boskoski-Costamagna trainer). Trainees with no experience in ERCP received either standard cannulation training or motion training before undergoing standard cannulation training on the mechanical simulator. Trainees were timed and graded on their performance in selective cannulation of four different papilla configurations. Results Thirty-six trainees (16 in the motion training group, 20 in the standard group) performed 720 timed attempts at cannulating the bile duct on the simulator. Successful cannulation was achieved in 698 of 720 attempts (96.9 %), with no significant difference between the two study groups ( P  = 0.37). Trainees in the motion training group had significantly lower median cannulation times compared to the standard group (36 vs. 48 seconds, P  = 0.001) and better technical performance on the first papilla type ( P  = 0.013). Conclusions Our findings suggest that motion training could be an innovative method aimed at accelerating the learning curve of novice trainees in the early phase of their training. Future studies are needed to establish its role in ERCP training programs.

Fork-tip needle biopsy versus fine-needle aspiration in endoscopic ultrasound-guided sampling of solid pancreatic masses: a randomized crossover study.

BACKGROUND: A novel fork-tip fine-needle biopsy (FNB) needle has recently been introduced for endoscopic ultrasound (EUS)-guided sampling. The aim of this study was to compare the performance of fork-tip FNB histology and standard fine-needle aspiration (FNA) cytology in the diagnosis of solid pancreatic masses. METHODS: A randomized crossover study was performed in patients referred for EUS-guided sampling. Three passes were taken with each needle in a randomized order. Only samples reported as diagnostic of malignancy were considered positive. The primary end point was the sensitivity of diagnosis of malignancy. Secondary end points included the amount of sample obtained, ease of diagnosis, duration of tissue sampling, pathologist viewing time, and cost. RESULTS: 108 patients were recruited. Median age was 69 years (range 30 - 87) and 57 were male; 85.2 % had a final diagnosis of malignancy. There were statistically significant differences in sensitivity (82 % [95 % confidence interval (CI) 72 % to 89 %] vs. 71 % [95 %CI 60 % to 80 %]), accuracy (84 % [95 %CI 76 % to 91 %] vs. 75 % [95 %CI 66 % to 83 %]), proportion graded as a straightforward diagnosis (69 % [95 %CI 60 % to 78 %] vs. 51 % [95 %CI 41 % to 61 %]), and median pathology viewing time (188 vs. 332 seconds) (P < 0.001) between FNB and FNA needles, respectively. There was no significant difference in cost between an FNB or FNA strategy. CONCLUSION: The diagnostic performance of the fork-tip FNB needle was significantly better than that of FNA; it was associated with ease of diagnosis, shorter pathological viewing times, and was cost neutral.

Endoscopic ultrasound-guided fine-needle biopsy is superior to fine-needle aspiration in assessing pancreatic neuroendocrine tumors.

Background and study aims Pancreatic neuroendocrine tumors (PanNETs) outcomes are dependent upon grading by Ki67. This study compared endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) to fine-needle aspiration (FNA) in assessing PanNETs. Patients and methods All pancreatic histology for PanNET between January 2009 and June 2017 was included if EUS sampling was performed prior to surgical resection. Ki67 and grade from FNA and FNB samples was compared to surgical histology using correlation coefficient and kappa values. Subgroup analysis was performed for purely solid lesions, lesions < 2 cm and FNB needle type. Results One hundred sixity-four patients had PanNET of which 57 underwent surgical resection. Thirty-five lesions underwent FNA and 26 FNB (4 had both) confirming PanNET. 23/ of 35 FNA samples reported Ki67/grading compared to all 26 FNB samples ( P  = 0.0006). Compared to surgical histology, Ki67 on FNA correlated poorly overall (r = -0.08), in solid lesions (r = -0.102) and lesions < 2 cm (r = -0.149) whereas FNB correlated moderately overall (r = 0.65), in solid lesions (r = 0.64) and lesions < 2 cm (r = 0.61). Tumor grade showed poor agreement (kappa) with FNA overall (0.026), in solid lesions (0.044) and lesions < 2 cm (0.00) whereas FNB showed moderate-good agreement overall (0.474), in solid lesions (0.58) and lesions < 2 cm (0.745). Fork-tip FNB needles Ki67 showed strong correlation with surgical histology (r = 0.788) compared to reverse bevel FNB needles (r = 0.521). Both FNB needles showed moderate agreement with tumor grade. Conclusion FNB samples were significantly more likely than FNA to provide adequate material for Ki67/grading and showed a closer match to surgical histology. FNB needle types require prospective investigation.

Impact of metal and plastic stents on endoscopic ultrasound-guided aspiration cytology and core histology of head of pancreas masses.

BACKGROUND: Stents are frequently placed in patients with biliary obstruction due to a mass in the head of the pancreas. The impact of plastic or self-expandable metal stents (SEMSs) on endoscopic ultrasound (EUS)-guided tissue sampling is unclear. This study aimed to assess, using strict pathological criteria, whether stents impair fine-needle aspiration (FNA) or fine-needle biopsy (FNB). METHODS: All patients with a solid mass in the head of the pancreas who underwent EUS-guided tissue sampling between 2010 and 2016 at our unit were included. Factors with possible impact on diagnostic performance were analyzed using logistic regression. Analysis was performed using both strict (malignant only) and less strict (suspicious for malignancy) cutoffs. RESULTS: Of 631 individuals undergoing 698 procedures, 535 (84.8 %) had a final diagnosis of malignancy, 141 had SEMS, 149 had plastic stents, and 341 had no stent. Using strict criteria, SEMS were associated with an increased occurrence of incorrect diagnosis of EUS tissue sampling, with an odds ratio (OR) of 1.96 (95 % confidence interval [CI] 1.24 - 3.10). Increasing tumor size (OR 0.72, 95 %CI 0.59 - 0.87), increasing number of passes (OR 0.84, 95 %CI 0.72 - 0.99), and fork-tip biopsy needle (OR 0.52, 95 %CI 0.31 - 0.86) were independently associated with a decrease in incorrect diagnosis. Repeat tissue sampling was more common with SEMSs (10.2 %) than with plastic stents (2.9 %) or no stents (4.5 %) (P < 0.02). CONCLUSION: SEMS use had a negative impact on tissue diagnosis in pancreatic head masses, whereas use of a fork-tip biopsy needle and increasing number of passes were independently associated with improved accuracy.

Novel temperature-controlled RFA probe for treatment of blocked metal biliary stents in patients with pancreaticobiliary cancers: initial experience.

BACKGROUND AND STUDY AIMS: Radiofrequency ablation (RFA) is used to treat blocked biliary stents in patients with pancreaticobiliary (PB) tumors with varying results. We report our experience with a novel temperature-controlled probe for treatment of blocked metal stents. PATIENTS AND METHODS: Patients with histologically proven PB cancers and a blocked biliary stents were treated using ELRATM electrode (Taewoong Medical) under fluoroscopic guidance. Demographics, clinical outcome, stricture diameter improvements, complications and mortality at 30 days were prospectively recorded. RESULTS: Nine procedures were performed on seven patients (4 male, 3 female); mean age 65.33 (range 56 - 82 years). Mean stricture diameter prior to RFA was 1.13 mm (SD ±â€Š0.54) and 4.42 mm (SD ±â€Š1.54) following RFA ( P  < 0.0001). Five of seven patients (71 %) required additional stents to ensure optimal drainage. There were no procedure-related complications. Mean follow-up was 193.55 days (range 31 - 540) and three of nine patients (33 %) died due to terminal cancer. CONCLUSION: These are the first reported data on use of a temperature-controlled RFA catheter in humans to treat blocked metal biliary stents. The device is safe but further randomized trials are required to establish the efficacy and survival benefits of this probe.

Multicenter experience from the UK and Ireland of use of lumen-apposing metal stent for transluminal drainage of pancreatic fluid collections.

BACKGROUND AND STUDY AIMS: Pancreatic fluid collection (PFC) is a common complication of pancreatitis for which endoscopic ultrasound-guided drainage is first-line treatment. A new single-device, lumen-apposing, covered self-expanding metal stent (LAMS) has been licensed for PFC drainage. We therefore present our multicenter experience with the LAMS for PFC drainage in a multicenter prospective case series to assess success and complication rates. PATIENTS AND METHODS: All adult patients from 11 tertiary centers who had LAMS placement for PFC from July 2015 to July 2016 were included. Data including indications, technical success, clinical success, collection resolution, stent removal, early and late adverse events (AEs), mortality and recurrence at 6 months were collected. RESULTS: 116 patients, median age 52.5 years (range 16 - 80) and 67 % male, were treated with a single LAMS in each case. The indication was walled off necrosis (WON) in 70 and pseudocyst in 46. Median size of the PFC was 11 cm (5 - 21 cm) and the estimated median necrotic volume in WON was 30 % (5 % - 90 %). Stent insertion was technically successful in 115 (99.1 %) and clinically successful in 109 (94 %). Early serious AEs (SAEs): n = 7 sepsis, n = 1 stent blockage with food, n = 1 stent migration requiring laparotomy, n = 1 stent dislodgement and n = 1 bleeding requiring emboliZation. Late AEs: n = 1 buried stent and n = 1 esophageal fistula. Non-procedure-related deaths: n = 3 (2.5 %). CONCLUSION: This multicenter case series demonstrates that use of the new LAMS is feasible, effective and relatively safe in draining PFC with a technical success rate of 99 % and cumulative SAE rate of 11.2 %.

Polyethylene Glycol 3350 With Electrolytes Versus Polyethylene Glycol 4000 for Constipation: A Randomized, Controlled Trial.

OBJECTIVE: The long-term efficacy and safety of polyethylene glycol (PEG) in constipated children are unknown, and a head-to-head comparison of the different PEG formulations is lacking. We aimed to investigate noninferiority of PEG3350 with electrolytes (PEG3350 + E) compared to PEG4000 without electrolytes (PEG4000). METHODS: In this double-blind trial, children aged 0.5 to 16 years with constipation, defined as a defecation frequency of <3 times per week, were randomized to receive either PEG3350 + E or PEG4000. Primary outcomes were change in total sum score (TSS) at week 52 compared to baseline, and dose range determination. TSS was the sum of the severity of 5 constipation symptoms rated on a 4-point scale (0-3). Noninferiority margin was a difference in TSS of ≤1.5 based on a 95%-confidence interval [CI]. Treatment success was defined as a defecation frequency of ≥3 per week with <1 episode of fecal incontinence. RESULTS: Ninety-seven subjects were included, of whom 82 completed the study. Mean reduction in TSS was -3.81 (95% CI: -4.96 to -2.65) and -3.74 (95%CI: -5.08 to -2.40), for PEG3350 + E and PEG4000, respectively. Noninferiority criteria were not met (maximum difference between groups: -1.81 to 1.68). Daily sachet use was: 0 to 2 years: 0.4 to 2.3 and 0.9 to 2.1; 2 to 4 years: 0.1 to 3.5 and 1.2 to 3.2; 4 to 8 years: 1.1 to 2.8 and 0.7 to 3.8; 8 to 16 years 0.6 to 3.7 and 1.0 to 3.7, in PEG3350 + E and PEG4000, respectively. Treatment success after 52 weeks was achieved in 50% and 45% of children, respectively (P = 0.69). Rates of adverse events were similar between groups, and no drug-related serious adverse events occurred. CONCLUSIONS: Noninferiority regarding long-term constipation-related symptoms of PEG3350 + E compared to PEG4000 was not demonstrated. However, analysis of secondary outcomes suggests similar efficacy and safety of these agents.

Efficacy and Safety of Digital Single-Operator Cholangioscopy for Difficult Biliary Stones.

BACKGROUND & AIMS: It is not clear whether digital single-operator cholangioscopy (D-SOC) with electrohydraulic and laser lithotripsy is effective in removal of difficult biliary stones. We investigated the safety and efficacy of D-SOC with electrohydraulic and laser lithotripsy in an international, multicenter study of patients with difficult biliary stones. METHODS: We performed a retrospective analysis of 407 patients (60.4% female; mean age, 64.2 years) who underwent D-SOC for difficult biliary stones at 22 tertiary centers in the United States, United Kingdom, or Korea from February 2015 through December 2016; 306 patients underwent electrohydraulic lithotripsy and 101 (24.8%) underwent laser lithotripsy. Univariate and multivariable analyses were performed to identify factors associated with technical failure and the need for more than 1 D-SOC electrohydraulic or laser lithotripsy session to clear the bile duct. RESULTS: The mean procedure time was longer in the electrohydraulic lithotripsy group (73.9 minutes) than in the laser lithotripsy group (49.9 minutes; P < .001). Ducts were completely cleared (technical success) in 97.3% of patients (96.7% of patients with electrohydraulic lithotripsy vs 99% patients with laser lithotripsy; P = .31). Ducts were cleared in a single session in 77.4% of patients (74.5% by electrohydraulic lithotripsy and 86.1% by laser lithotripsy; P = .20). Electrohydraulic or laser lithotripsy failed in 11 patients (2.7%); 8 patients were treated by surgery. Adverse events occurred in 3.7% patients and the stone was incompletely removed from 6.6% of patients. On multivariable analysis, difficult anatomy or cannulation (duodenal diverticula or altered anatomy) correlated with technical failure (odds ratio, 5.18; 95% confidence interval, 1.26-21.2; P = .02). Procedure time increased odds of more than 1 session of D-SOC electrohydraulic or laser lithotripsy (odds ratio, 1.02; 95% confidence interval, 1.01-1.03; P < .001). CONCLUSIONS: In a multicenter, international, retrospective analysis, we found D-SOC with electrohydraulic or laser lithotripsy to be effective and safe in more than 95% of patients with difficult biliary stones. Fewer than 5% of patients require additional treatment with surgery and/or extracorporeal shockwave lithotripsy to clear the duct.

A comparison of outcomes between a lumen-apposing metal stent with electrocautery-enhanced delivery system and a bi-flanged metal stent for drainage of walled-off pancreatic necrosis.

BACKGROUND AND STUDY AIMS: Bi-flanged metal stents (BFMS) have shown promise in the drainage of walled-off pancreatic necrosis (WON), but their placement requires multiple steps and the use of other devices. More recently, a novel device consisting of a combined lumen-apposing metal stent (LAMS) and electrocautery-enhanced delivery system has been introduced. The aim of this study was to compare the placement and outcomes of the two devices. PATIENTS AND METHODS: This was a retrospective review of consecutive patients undergoing endoscopic ultrasound-guided placement of BFMS or LAMS for drainage of symptomatic WON. Data from procedures between October 2012 and December 2016 were taken from a prospectively maintained database. We compared technical and clinical success, procedure time, costs, and composite end point of significant events (adverse events, stent migration, additional percutaneous drainage) between BFMS and LAMS. RESULTS: 72 consecutive patients underwent placement of BFMS (40 patients, 44 stents) or LAMS (32 patients, 33 stents). Technical success was 91 % for BFMS and 97 % for LAMS. Clinical success was 65 % vs. 78 %, respectively. Median in-room procedure time was significantly shorter in the LAMS group (45 minutes [range 30 - 80]) than in the BFMS group (62.5 minutes [range 35 - 135]; P  < 0.001) and fewer direct endoscopic necrosectomies (DEN) were performed (median 1 [0 - 2.0] vs. 2 [0 - 3.7], respectively; P  = 0.005). If only inpatients were considered (35 BFMS and 19 LAMS), there was no significant difference in DEN 2 (range 0 - 11) and 2 (range 0 - 8), respectively. The composite end point of 32 % vs. 24 % was not significantly different. Median procedural costs for all patients with successful stent placement for WON treatment was €4427 (range 1630 - 12 926) for BFMS vs. €3500 (range 2509 - 13 393) for LAMS ( P  = 0.10). CONCLUSION: LAMS was superior to BFMS in terms of procedure time, with comparable adverse events, success, and costs.