Endoscopic Ultrasound-Guided Biliary Drainage of First Intent With a Lumen-Apposing Metal Stent vs Endoscopic Retrograde Cholangiopancreatography in Malignant Distal Biliary Obstruction: A Multicenter Randomized Controlled Study (ELEMENT Trial).

BACKGROUND & AIMS: Endoscopic ultrasound-guided choledochoduodenostomy with a lumen-apposing metal stent (EUS-CDS) is a promising modality for management of malignant distal biliary obstruction (MDBO) with potential for better stent patency. We compared its outcomes with endoscopic retrograde cholangiopancreatography with metal stenting (ERCP-M). METHODS: In this multicenter randomized controlled trial, we recruited patients with MDBO secondary to borderline resectable, locally advanced, or unresectable peri-ampullary cancers across 10 Canadian institutions and 1 French institution. This was a superiority trial with a noninferiority assessment of technical success. Patients were randomized to EUS-CDS or ERCP-M. The primary end point was the rate of stent dysfunction at 1 year, considering competing risks of death, clinical failure, and surgical resection. Analyses were performed according to intention-to-treat principles. RESULTS: From February 2019 to February 2022, 144 patients were recruited; 73 were randomized to EUS-CDS and 71 were randomized to ERCP-M. The mean (SD) procedure time was 14.0 (11.4) minutes for EUS-CDS and 23.1 (15.6) minutes for ERCP-M (P < .01); 40% of the former was performed without fluoroscopy. Technical success was achieved in 90.4% (95% CI, 81.5% to 95.3%) of EUS-CDS and 83.1% (95% CI, 72.7% to 90.1%) of ERCP-M with a risk difference of 7.3% (95% CI, -4.0% to 18.8%) indicating noninferiority. Stent dysfunction occurred in 9.6% vs 9.9% of EUS-CDS and ERCP-M cases, respectively (P = .96). No differences in adverse events, pancreaticoduodenectomy and oncologic outcomes, or quality of life were noted. CONCLUSIONS: Although not superior in stent function, EUS-CDS is an efficient and safe alternative to ERCP-M in patients with MDBO. These findings provide evidence for greater adoption of EUS-CDS in clinical practice as a complementary and exchangeable first-line modality to ERCP in patients with MDBO. CLINICALTRIALS: gov, Number: NCT03870386.

Aspirin exposure and its association with metal stent patency in malignant distal biliary obstruction: a large international multicenter propensity score-matched study.

BACKGROUND AND AIMS: Stent dysfunction is common after ERCP with self-expandable metal stent (SEMS) insertion for malignant distal biliary obstruction (MDBO). Chronic aspirin (acetylsalicylic acid; ASA) exposure has been previously shown to potentially decrease this risk. We aim to further ascertain the protective effect of ASA and to identify other predictors of stent dysfunction. METHODS: This multicenter retrospective cohort study was conducted at 9 sites in Canada and 1 in the United States. Patients with MDBO who underwent ERCP with SEMS placement between January 2014 and December 2019 were included and divided into 2 cohorts: ASA exposed (ASA-E) and ASA unexposed (ASA-U). Propensity-score matching (PSM) was performed to limit selection bias. Matched variables were age, sex, tumor stage, and type of metal stent. The primary outcome was the hazard rate of stent dysfunction. A multivariable Cox proportional hazards model was used to identify independent predictors of stent dysfunction. RESULTS: Of 1396 patients assessed, after PSM 496 patients were analyzed (248 ASA-E and 248 ASA-U). ERCP with SEMS placement was associated with a high clinical success of 82.2% in ASA-E and 81.2% in ASA-U cohorts (P = .80). One hundred eighty-four patients had stent dysfunction with a mean stent patency time of 229.9 ± 306.2 days and 245.4 ± 241.4 days in ASA-E and ASA-U groups, respectively (P = .52). On multivariable analysis, ASA exposure did not protect against stent dysfunction (hazard ratio [HR], 1.25; 95% confidence interval [CI], .96-1.63). An etiology of pancreatic cancer (HR, 1.36; 95% CI, 1.15-1.61) predicted stent dysfunction, whereas cancer therapy was protective (HR, .73; 95% CI, .55-.96). Chronic ASA use was not associated with an increased risk for adverse events including bleeding, post-ERCP pancreatitis, and perforation. CONCLUSIONS: In this large, multicenter study using PSM, chronic exposure to ASA did not protect against stent dysfunction in MDBO. Instead, the analysis revealed that the etiology of pancreatic cancer was an independent predictor of stent dysfunction and cancer therapy was protective.

Endoscopic ultrasound (EUS)-guided fine needle biopsy alone vs. EUS-guided fine needle aspiration with rapid onsite evaluation in pancreatic lesions: a multicenter randomized trial.

BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the standard in the diagnosis of solid pancreatic lesions, in particular when combined with rapid onsite evaluation of cytopathology (ROSE). More recently, a fork-tip needle for core biopsy (FNB) has been shown to be associated with excellent diagnostic yield. EUS-FNB alone has however not been compared with EUS-FNA + ROSE in a large clinical trial. Our aim was to compare EUS-FNB alone to EUS-FNA + ROSE in solid pancreatic lesions. METHODS: A multicenter, non-inferiority, randomized controlled trial involving seven centers was performed. Solid pancreatic lesions referred for EUS were considered for inclusion. The primary end point was diagnostic accuracy. Secondary end points included sensitivity/specificity, mean number of needle passes, and cost. RESULTS: 235 patients were randomized: 115 EUS-FNB alone and 120 EUS-FNA + ROSE. Overall, 217 patients had malignant histology. The diagnostic accuracy for malignancy of EUS-FNB alone was non-inferior to EUS-FNA + ROSE at 92.2 % (95 %CI 86.6 %-96.9 %) and 93.3 % (95 %CI 88.8 %-97.9 %), respectively (P = 0.72). Diagnostic sensitivity for malignancy was 92.5 % (95 %CI 85.7 %-96.7 %) for EUS-FNB alone vs. 96.5 % (93.0 %-98.6 %) for EUS-FNA + ROSE (P = 0.46), while specificity was 100 % in both. Adequate histological yield was obtained in 87.5 % of the EUS-FNB samples. The mean (SD) number of needle passes and procedure time favored EUS-FNB alone (2.3 [0.6] passes vs. 3.0 [1.1] passes [P < 0.001]; and 19.3 [8.0] vs. 22.7 [10.8] minutes [P = 0.008]). EUS-FNB alone cost on average 45 US dollars more than EUS-FNA + ROSE. CONCLUSION: EUS-FNB alone is non-inferior to EUS-FNA + ROSE and is associated with fewer needle passes, shorter procedure time, and excellent histological yield at comparable cost.

Digital Cholangioscopic Interpretation: When North Meets the South.

BACKGROUND: Digital single-operator cholangioscopy (DSOC) (SpyGlass DS™, Boston Scientific, MA, USA) allows for high-definition imaging of the biliary tree. The superior visualization has led to the development of two different sets of criteria to evaluate and classify indeterminate biliary strictures: the Monaco criteria and the criteria in Carlos Robles-Medranda's publication (CRM). Our objective was to assess the interrater agreement (IA) of DSOC interpretation for indeterminate biliary strictures using the two newly published criteria. METHODS: Forty de-identified DSOC video recordings were sent to 15 interventional endoscopists with experience in cholangioscopy. They were asked to score the videos based on the presence of Monaco Classification criteria: stricture, lesion, mucosal changes, papillary projections, ulceration, white linear bands or rings, and vessels. Next, they scored the videos using CRM criteria: villous pattern, polypoid pattern, inflammatory pattern, flat pattern, ulcerate pattern and honeycomb pattern. The endoscopists then diagnosed the recordings as neoplastic or non-neoplastic based on the criteria. Intraclass correlation (ICC) analysis was done to evaluate interrater agreement for both criteria set and final diagnosis. RESULTS: Recordings of 26 malignant lesions and 14 benign lesions were scored. The IA using both the Monaco criteria and CRM criteria ranged from poor to excellent (range 0.1-0.76) and (range 0.1-0.62), respectively. Within the Monaco criteria, IA was excellent for lesion (0.75) and fingerlike papillary projections (0.74); good for tortuous vessels (0.7), mucosal features (0.62), uniform papillary projections (0.53), and ulceration (0.58); and fair for white linear bands (0.4). Within the CRM criteria, the IA was good for villous pattern (0.62), flat pattern (0.62), and honeycomb pattern; fair for ulcerated pattern (0.56), polypoid pattern (0.52) and inflammatory pattern (0.54). The diagnostic IA using Monaco criteria was good (0.65), while the diagnostic IA using CRM was fair (0.58). The overall diagnostic accuracy using the Monaco classification was 61% and CRM criteria were 57%. CONCLUSION: The IOA and accuracy rate of DSOC using visual criteria from both Monaco Criteria and CRM are similar. However, some criteria from both sets suffer from poor IA, thus affecting the overall diagnostic accuracy. More formal training and refinements in visual criteria with additional validation are needed to improve diagnostic accuracy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02166099.

Competence in Endoscopic Ultrasound and Endoscopic Retrograde Cholangiopancreatography, From Training Through Independent Practice.

BACKGROUND & AIMS: It is unclear whether participation in competency-based fellowship programs for endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) results in high-quality care in independent practice. We measured quality indicator (QI) adherence during the first year of independent practice among physicians who completed endoscopic training with a systematic assessment of competence. METHODS: We performed a prospective multicenter cohort study of invited participants from 62 training programs. In phase 1, 24 advanced endoscopy trainees (AETs), from 20 programs, were assessed using a validated competence assessment tool. We used a comprehensive data collection and reporting system to create learning curves using cumulative sum analysis that were shared with AETs and trainers quarterly. In phase 2, participating AETs entered data into a database pertaining to every EUS and ERCP examination during their first year of independent practice, anchored by key QIs. RESULTS: By the end of training, most AETs had achieved overall technical competence (EUS 91.7%, ERCP 73.9%) and cognitive competence (EUS 91.7%, ERCP 94.1%). In phase 2 of the study, 22 AETs (91.6%) participated and completed a median of 136 EUS examinations per AET and 116 ERCP examinations per AET. Most AETs met the performance thresholds for QIs in EUS (including 94.4% diagnostic rate of adequate samples and 83.8% diagnostic yield of malignancy in pancreatic masses) and ERCP (94.9% overall cannulation rate). CONCLUSIONS: In this prospective multicenter study, we found that although competence cannot be confirmed for all AETs at the end of training, most meet QI thresholds for EUS and ERCP at the end of their first year of independent practice. This finding affirms the effectiveness of training programs. Clinicaltrials.gov ID NCT02509416.

Setting minimum standards for training in EUS and ERCP: results from a prospective multicenter study evaluating learning curves and competence among advanced endoscopy trainees.

BACKGROUND AND AIMS: Minimum EUS and ERCP volumes that should be offered per trainee in "high quality" advanced endoscopy training programs (AETPs) are not established. We aimed to define the number of procedures required by an "average" advanced endoscopy trainee (AET) to achieve competence in technical and cognitive EUS and ERCP tasks to help structure AETPs. METHODS: American Society for Gastrointestinal Endoscopy (ASGE)-recognized AETPs were invited to participate; AETs were graded on every fifth EUS and ERCP examination using a validated tool. Grading for each skill was done using a 4-point scoring system, and learning curves using cumulative sum analysis for overall, technical, and cognitive components of EUS and ERCP were shared with AETs and trainers quarterly. Generalized linear mixed-effects models with a random intercept for each AET were used to generate aggregate learning curves, allowing us to use data from all AETs to estimate the average learning experience for trainees. RESULTS: Among 62 invited AETPs, 37 AETs from 32 AETPs participated. Most AETs reported hands-on EUS (52%, median 20 cases) and ERCP (68%, median 50 cases) experience before starting an AETP. The median number of EUS and ERCPs performed per AET was 400 (range, 200-750) and 361 (range, 250-650), respectively. Overall, 2616 examinations were graded (EUS, 1277; ERCP-biliary, 1143; pancreatic, 196). Most graded EUS examinations were performed for pancreatobiliary indications (69.9%) and ERCP examinations for ASGE biliary grade of difficulty 1 (72.1%). The average AET achieved competence in core EUS and ERCP skills at approximately 225 and 250 cases, respectively. However, overall technical competence was achieved for grade 2 ERCP at about 300 cases. CONCLUSION: The thresholds provided for an average AET to achieve competence in EUS and ERCP may be used by the ASGE and AETPs in establishing the minimal standards for case volume exposure for AETs during their training. (Clinical trial registration number: NCT02509416.).

Multidisciplinary treatment of T1a adenocarcinoma in Barrett's esophagus: contemporary comparison of endoscopic and surgical treatment in physiologically fit patients.

BACKGROUND: Previous reports comparing endoscopic therapy (ET) and surgical therapy (ST) have predominantly assessed patients with high-grade dysplasia. The study aim was to compare ET to ST in physiologically fit patients with cT1a adenocarcinoma (EAC). METHODS: Review of two prospective databases yielded 100 patients presenting with clinical cT1a EAC between 2000 and 2013. Only physiologically fit patients who were candidates for either treatment were analyzed. RESULTS: Presenting patient characteristics were similar between ET (n = 36) and ST groups (n = 49). Surgical patients were less likely to be staged with EMR (43 vs 100 %) and were associated with mass lesions >1 cm at EGD (p = 0.01), multifocal EAC (p = 0.03), and positive margins for EAC on EMR (p < 0.05). On multivariate analysis, only multifocal HGD was an independent factor for surgery. Following esophagectomy, R0 resection rates for Barrett's esophagus and cancer were 100 %. Incidence of surgery decreased over the study period from 85 to 25 %. All ET patients had EMR, and 28 patients underwent additional ablative therapies for Barrett's esophagus. Following ET, eradication rates of EAC, dysplasia, and BE were 92, 81, and 53 %, respectively. Morbidity rates were comparable between groups (ST 51 % vs ET 39 %, p = 0.31). In-hospital mortality rate was zero in each group. Recurrence rates in ST and ET group were 2 and 11 % (p = 0.08). In the ET group, two patients with endoluminal cancer recurrence after complete eradication underwent esophagectomy. Age-adjusted overall survival was comparable. CONCLUSION: In high-volume esophageal centers, ST and ET provide equally safe and effective treatment for cT1a EAC in medically fit patients. While the results of this study provide a historical perspective and clearly demonstrate an evolution toward ET over time, the appropriate treatment modality is best selected in a multidisciplinary fashion with EMR providing the most accurate staging. In endoscopically treated patients, indefinite endoscopic follow-up required, however, standardized long-term follow-up protocols are needed.

Validation of the diagnostic accuracy of probe-based confocal laser endomicroscopy for the characterization of indeterminate biliary strictures: results of a prospective multicenter international study.

BACKGROUND: Characterization of indeterminate biliary strictures remains problematic. Tissue sampling is the criterion standard for confirming malignancy but has low sensitivity. Probe-based confocal laser endomicroscopy (pCLE) showed excellent sensitivity in a registry; however, it has not been validated in a prospective study. OBJECTIVE: To prospectively validate pCLE in real time during ERCP for indeterminate biliary strictures. DESIGN: Prospective, international, multicenter study. SETTING: Six academic centers. PATIENTS: A total of 136 patients with indeterminate biliary strictures. INTERVENTIONS: Investigators provided a presumptive diagnosis based on the patient history, ERCP impression, and pCLE during the procedure before and after tissue sampling results were available. A presumptive diagnosis also was made separately by a blinded investigator during ERCP and after tissue sampling to estimate care without pCLE. Follow-up was at least 6 months. MAIN OUTCOME MEASUREMENTS: Accuracy, sensitivity, and specificity during ERCP alone, ERCP with pCLE, and ERCP with pCLE and tissue sampling. RESULTS: A total of 112 patients were evaluated (71 with malignant lesions). Tissue sampling alone was 56% sensitive, 100% specific, and 72% (95% confidence interval [CI], 63%-80%) accurate. pCLE with ERCP was 89% sensitive, 71% specific, and 82% (95% CI, 74%-89%) accurate. After tissue sampling returned, strictures could be characterized with 88% (95% CI, 81%-94%) accuracy. LIMITATIONS: No randomization of care maps. pCLE not blinded. CONCLUSION: pCLE provided a more accurate and sensitive diagnosis of cholangiocarcinoma compared with tissue sampling alone. Incorporation of pCLE into the diagnostic armamentarium of patients with indeterminate biliary strictures may allow for a more accurate assessment, potentially reducing delays in diagnosis and costly repeat testing. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01392274.).

Endoscopic treatment of nonstricture-related benign biliary diseases using covered self-expandable metal stents.

BACKGROUND AND STUDY AIMS: Nonstricture benign biliary diseases (BBDs) such as leaks, perforations, and bleeding, have been traditionally managed by placement of one or more plastic stents. Emerging data support the use of covered, self-expandable, metal stents (CSEMSs). The aim of this study was to assess the outcomes of endoscopic temporary placement of CSEMS in patients with nonstricture BBD. PATIENTS AND METHODS: This was a retrospective study of CSEMS placement for BBD between May 2005 and August 2013 at two tertiary care centers. The main outcome measures were resolution of perforation, bleeding, leak, and adverse events related to CSEMS treatment. RESULTS: A total of 87 patients were included (median age 62 years [range 18 - 86]). Indications for stent placement were bile leaks (n = 35, 40 %), bleeding (n = 27, 31 %), perforation (n = 18, 21 %), and other conditions (n = 7, 8 %). Fully and partially covered 8 - 10-mm diameter CSEMS were placed and subsequently removed in all 87 patients (100 %). Resolution of the underlying problem was achieved for 33 bile leaks (94 %), 25 bleedings (93 %), 18 perforations (100 %), and for 3 cases with other indications (43 %). The median duration of stenting was 9 weeks in patients with biliary leaks, 3 weeks for bleeding, and 9.5 weeks for perforations. Median follow-up was 82 weeks after stent removal. Seven adverse events occurred, including cholangitis in six patients (7 %), and tissue hyperplasia leading to difficulty in the removal of a partially covered SEMS in one patient. CONCLUSIONS: Nonstricture BBD can be effectively and safely treated with the short term placement of CSEMS. .

Endoscopic treatment of benign biliary strictures using covered self-expandable metal stents (CSEMS).

BACKGROUND AND AIMS: Traditional endoscopic management of benign biliary strictures (BBS) consists of placement of one or more plastic stents. Emerging data support the use of covered self-expandable metal stents (CSEMS). We sought to assess outcome of endoscopic temporary placement of CSEMS in patients with BBS. METHODS: This was a retrospective study of CSEMS placement for BBS between May 2005 and July 2012 from two tertiary care centers. A total of 145 patients (81 males, median age 59 years) with BBS were identified; 73 of which were classified as extrinsic and were caused by chronic pancreatitis, and 70 were intrinsic. Main outcome measures were resolution of stricture and adverse events (AEs) due to self-expandable metal stents (SEMS)-related therapy. RESULTS: Fully covered and partially covered 8-10 mm diameter SEMS were placed and subsequently removed in 121/125 (97 %) attempts in BBS (failure to remove four partially covered stents). Stricture resolution occurred in 83/125 (66 %) patients after a median stent duration of 26 weeks (median follow-up 90 weeks). Resolution of extrinsic strictures was significantly lower compared to intrinsic strictures (31/65, 48 % vs. 52/60, 87 %, p = 0.004) despite longer median stent duration (30 vs. 20 weeks). Thirty-seven AEs occurred in 25 patients (17 %), with 12 developing multiple AEs including cholangitis (n = 17), pancreatitis (n = 5), proximal stent migration (n = 3), cholecystitis (n = 2), pain requiring SEMS removal and/or hospitalization (n = 3), inability to remove (n = 4), and new stricture formation (n = 3). CONCLUSIONS: Benign biliary strictures can be effectively treated with CSEMS. Successful resolution of biliary strictures due to extrinsic disease is seen significantly less often than those due to intrinsic disease. Removal is successful in all patients with fully covered SEMS.

Determining when endoscopic ultrasound changes management for patients with pancreatic cystic neoplasms.

INTRODUCTION: Pancreatic cystic neoplasms (PCNs) are being incidentally detected at an increased rate due to increased CT and MRI usage. EUS is an emerging tool that can differentiate between benign and malignant features of pancreatic cysts. We hoped to identify the specific cross-sectional imaging findings and patient characteristics that warrant EUS referral. METHODS: We conducted a retrospective case-control chart review, evaluating patients, who were diagnosed with pancreatic cysts and underwent EUS between January 1, 2010 and December 31, 2017. RESULTS: EUS was found to change management when CT imaging found cyst size > 4 cm (OR = 4.07, p < 0.01), cyst size > 3 cm (OR = 3.79, p < 0.001) and associated solid component to the cyst (OR = 5.95, p < 0.01). Additionally, patient characteristics, including age less than 50 years, male sex and 10-pack year smoking history were significantly associated with EUS change in management. DISCUSSION: Our findings suggest that EUS referral should be coordinated based on the findings of specific HRFs, with support from high risk patient characteristics, rather than the accumulation of multiple HRFs, as suggested by existing guidelines.

ELEMENT TRIAL: study protocol for a randomized controlled trial on endoscopic ultrasound-guided biliary drainage of first intent with a lumen-apposing metal stent vs. endoscopic retrograde cholangio-pancreatography in the management of malignant distal biliary obstruction.

BACKGROUND & AIMS: Endoscopic ultrasound guided-biliary drainage (EUS-BD) is a promising alternative to endoscopic retrograde cholangiopancreatography (ERCP); however, its growth has been limited by a lack of multicenter randomized controlled trials (RCT) and dedicated devices. A dedicated EUS-BD lumen- apposing metal stent (LAMS) has recently been developed with the potential to greatly facilitate the technique and safety of the procedure. We aim to compare a first intent approach with EUS-guided choledochoduodenostomy with a dedicated biliary LAMS vs. standard ERCP in the management of malignant distal biliary obstruction. METHODS: The ELEMENT trial is a multicenter single-blinded RCT involving 130 patients in nine Canadian centers. Patients with unresectable, locally advanced, or borderline resectable malignant distal biliary obstruction meeting the inclusion and exclusion criteria will be randomized to EUS-choledochoduodenostomy using a LAMS or ERCP with traditional metal stent insertion in a 1:1 proportion in blocks of four. Patients with hilar obstruction, resectable cancer, or benign disease are excluded. The primary endpoint is the rate of stent dysfunction needing re-intervention. Secondary outcomes include technical and clinical success, interruptions in chemotherapy, rate of surgical resection, time to stent dysfunction, and adverse events. DISCUSSION: The ELEMENT trial is designed to assess whether EUS-guided choledochoduodenostomy using a dedicated LAMS is superior to conventional ERCP as a first-line endoscopic drainage approach in malignant distal biliary obstruction, which is an important and timely question that has not been addressed using an RCT study design. TRIAL REGISTRATION: Registry name: ClinicalTrials.gov. Registration number: NCT03870386. Date of registration: 03/12/2019.