International Consensus Recommendations for Safe Use of LAMS for On- and Off-Label Indications Using a Modified Delphi Process.

INTRODUCTION: The study aimed to develop international consensus recommendations on the safe use of lumen-apposing metal stents (LAMSs) for on- and off-label indications. METHODS: Based on the available literature, statements were formulated and grouped into the following categories: general safety measures, peripancreatic fluid collections, endoscopic ultrasound (EUS)-biliary drainage, EUS-gallbladder drainage, EUS-gastroenterostomy, and gastric access temporary for endoscopy. The evidence level of each statement was determined using the Grading of Recommendations Assessment, Development, and Evaluation methodology.International LAMS experts were invited to participate in a modified Delphi process. When no 80% consensus was reached, the statement was modified based on expert feedback. Statements were rejected if no consensus was reached after the third Delphi round. RESULTS: Fifty-six (93.3%) of 60 formulated statements were accepted, of which 35 (58.3%) in the first round. Consensus was reached on the optimal learning path, preprocedural imaging, the need for airway protection and essential safety measures during the procedure, such as the use of Doppler, and measurement of the distance between the gastrointestinal lumen and the target structure. Specific consensus recommendations were generated for the different LAMS indications, covering, among others, careful patient selection, the preferred size of the LAMS, the need for antibiotics, the preferred anatomic location of the LAMS, the need for coaxial pigtail placement, and the appropriate management of LAMS-related adverse events. DISCUSSION: Through a modified international Delphi process, we developed general and indication-specific experience- and evidence-based recommendations on the safe use of LAMS.

The effect of steroid therapy on pancreatic exocrine function in autoimmune pancreatitis.

BACKGROUND/OBJECTIVES: Autoimmune pancreatitis (AIP) is a steroid-responsive inflammatory disease of the pancreas. Few studies investigated pancreatic exocrine function (PEF) in patients suffering from AIP and no definitive data are available on the effect of steroids in PEF recovery. Aim of the study is the evaluation of severe pancreatic insufficiency (sPEI) prevalence in AIP at clinical onset and after steroid treatment. METHODS: 312 Patients with diagnosis of AIP between January 1st, 2010 and December 31st, 2020 were identified in our prospectively maintained register. Patients with a pre-steroid treatment dosage of fecal elastase-1 (FE-1) were included. Changes in PEF were evaluated in patients with available pre- and post-treatment FE (between 3 and 12 months after steroid). RESULTS: One-hundred-twenty-four patients were included, with a median FE-1 of 122 (Q1-Q3: 15-379) µg/g at baseline. Fifty-nine (47.6 %) had sPEI (FE-1<100 µg/g). Univariable analysis identified type 1 AIP, radiological involvement of the head of the pancreas (diffuse involvement of the pancreas or focal involvement of the head), weight loss, age and diabetes as associated with a greater risk of sPEI. However, at multivariable analysis, only the involvement of the head of the pancreas was identified as independent risk factor for sPEI. After steroids, mean FE-1 changed from 64 (15-340) to 202 (40-387) µg/g (P = 0.058) and head involvement was the only predictor of improvement of sPEI. CONCLUSION: The inflammatory involvement of the head of the pancreas is associated with PEF severity, as well as PEF improvement after treatment with steroids in patients with AIP.

Comparative diagnostic yield of different endoscopic techniques for tissue sampling of upper gastrointestinal subepithelial lesions: a network meta-analysis.

BACKGROUND: There is limited evidence on the comparative diagnostic performance of endoscopic tissue sampling techniques for subepithelial lesions. We performed a systematic review with network meta-analysis to compare these techniques. METHODS: A systematic literature review was conducted for randomized controlled trials (RCTs) comparing the sample adequacy and diagnostic accuracy of bite-on-bite biopsy, mucosal incision-assisted biopsy (MIAB), endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), and EUS-guided fine-needle biopsy (FNB). Results were expressed as relative risk (RR) and 95%CI. RESULTS: Eight RCTs were identified. EUS-FNB was significantly superior to EUS-FNA in terms of sample adequacy (RR 1.20 [95%CI 1.05-1.45]), whereas none of the other techniques significantly outperformed EUS-FNA. Additionally, bite-on-bite biopsy was significantly inferior to EUS-FNB (RR 0.55 [95%CI 0.33-0.98]). Overall, EUS-FNB appeared to be the best technique (surface under cumulative ranking [SUCRA] score 0.90) followed by MIAB (SUCRA 0.83), whereas bite-on-bite biopsy showed the poorest performance. When considering lesions <20 mm, MIAB, but not EUS-FNB, showed significantly higher accuracy rates compared with EUS-FNA (RR 1.68 [95%CI 1.02-2.88]). Overall, MIAB ranked as the best intervention for lesions <20 mm (SUCRA score 0.86 for adequacy and 0.91 for accuracy), with EUS-FNB only slightly superior to EUS-FNA. When rapid on-site cytological evaluation (ROSE) was available, no difference between EUS-FNB, EUS-FNA, and MIAB was observed. CONCLUSION: EUS-FNB and MIAB appeared to provide better performance, whereas bite-on-bite sampling was significantly inferior to the other techniques. MIAB seemed to be the best option for smaller lesions, whereas EUS-FNA remained competitive when ROSE was available.

Lumen-apposing metal stents for the treatment of pancreatic and peripancreatic fluid collections and bleeding risk: a propensity matched study.

INTRODUCTION: Endoscopic ultrasound (EUS)-guided drainage of symptomatic pancreatic fluid collections (PFCs) using the Hot-Axios device has recently been associated with a significant risk of bleeding. This adverse event (AE) seems to occur less frequently with the use of a different device, the Spaxus stent. The aim of the current study was to compare the rates of bleeding between the two stents. METHODS: Patients admitted for treatment of PFCs by EUS plus lumen-apposing metal stent in 18 endoscopy referral centers between 10 July 2019 and 28 February 2022 were identified and their outcomes compared using a propensity-matching analysis. RESULTS: 363 patients were evaluated. After a 1-to-1 propensity score match, 264 patients were selected (132 per group). The technical and clinical success rates were comparable between the two groups. Significantly more bleeding requiring transfusion and/or intervention occurred in the Hot-Axios group than in the Spaxus group (6.8% vs. 1.5%; P = 0.03); stent type was a significant predictor of bleeding in both univariate and multivariate regression analyses (P = 0.03 and 0.04, respectively). Bleeding necessitating arterial embolization did not however differ significantly between the two groups (3.0% vs. 0%; P = 0.12). In addition, the Hot-Axios was associated with a significantly higher rate of overall AEs compared with the Spaxus stent (9.8% vs. 3.0%; P = 0.04). CONCLUSION: Our study showed that, in patients with PFCs, bleeding requiring transfusion and/or intervention occurred significantly more frequently with use of the Hot-Axios stent than with the Spaxus stent, although this was not the case for bleeding requiring embolization.

Partially covered versus uncovered pyloro-duodenal stents for unresectable malignant gastric outlet obstruction: Randomized controlled study.

OBJECTIVES: The aim of the current study was to compare the efficacy of partially covered duodenal stent (PCDS) vs. uncovered duodenal stent (UCDS) in patients suffering from unresectable primary malignant gastric outlet obstruction (GOO). METHODS: This was a prospective international randomized controlled study conducted in 10 high-volume institutions. Consecutive patients suffering from malignant GOO were recruited. The primary outcome measurement was the reintervention rate. Secondary outcomes included technical and clinical success, 30-day adverse events, 30-day mortality, causes of stent dysfunction, and the duration of stent patency. RESULTS: Between March 2017 and October 2020, 115 patients (59 PCDS, 56 UCDS) were recruited. The 1-year reintervention was not significantly different (PCDS vs. UDCS = 12/59, 20.3% vs. 14/56, 25%, P = 0.84). There was a trend to fewer patients with tumor ingrowth in the PCDS group (6/59 [10.2%]) vs. 13/56 [23.2%], P = 0.07). There were no significant differences in the technical success (100% vs. 100%, P = 1), clinical success (91.5% vs. 98.2%, P = 0.21), procedural time (21.5 [interquartile range [IQR] 17-30] vs. 20.0 [IQR 15-34.75], P = 0.62), hospital stay (4 [IQR 3-12] vs. 5 [IQR 3-8] days, P = 0.81), 30-day adverse events (18.6% vs. 14.3%, P = 0.62), or 30-day mortality (6.8% vs. 5.2%, P = 1.00). CONCLUSION: The use of PCDS was associated with a lower risk of tumor ingrowth but did not improve on reintervention rates or stent patency. Both kinds of stents could be used in this group of patients.

Endoscopic ultrasound-guided gallbladder drainage as a first approach for jaundice palliation in unresectable malignant distal biliary obstruction: Prospective study.

OBJECTIVES: Endoscopic retrograde cholangiopancreatography (ERCP) represents the gold standard for jaundice palliation in patients with distal malignant biliary obstruction (DMBO). Biliary drainage using electrocautery lumen apposing metal stent (EC-LAMS) is currently a well-established procedure when ERCP fails. In a palliative setting the endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) could represent an easy and valid option. We performed a prospective study with a new EC-LAMS with the primary aim to assess the clinical success rate of EUS-GBD as a first-line approach to the palliation of DMBO. METHODS: In all, 37 consecutive patients undergoing EUS-GBD with a new EC-LAMS were prospectively enrolled. Clinical success was defined as bilirubin level decrease >15% within 24 h and >50% within 14 days after EC-LAMS placement. RESULTS: The mean age was 73.5 ± 10.8 years; there were 17 male patients (45.9%). EC-LAMS placement was technically feasible in all patients (100%) and the clinical success rate was 100%. Four patients (10.8%) experienced adverse events, one bleeding, one food impaction, and two cystic duct obstructions because of disease progression. No stent-related deaths were observed. The mean hospitalization was 7.7 ± 3.4 days. Median overall survival was 4 months (95% confidence interval 1-8). CONCLUSION: Endoscopic ultrasound-guided gallbladder drainage with the new EC-LAMS is a valid option in palliative endoscopic biliary drainage as a first-step approach in low survival patients with malignant jaundice unfit for surgery. A smaller diameter EC-LAMS should be preferred, particularly if the drainage is performed through the stomach, to avoid potential food impaction, which could result in stent dysfunction.

Endoscopic Treatment of Large Bile Duct Stones: A Systematic Review and Network Meta-Analysis.

BACKGROUND & AIMS: Several endoscopic methods have been proposed for the treatment of large biliary stones. We assessed the comparative efficacy of these treatments through a network meta-analysis. METHODS: Nineteen randomized controlled trials (2752 patients) comparing different treatments for management of large bile stones (>10 mm) (endoscopic sphincterotomy, balloon sphincteroplasty, sphincterotomy followed by endoscopic papillary large balloon dilation [S+EPLBD], mechanical lithotripsy, single-operator cholangioscopy [SOC]) with each other were identified. Study outcomes were the success rate of stone removal and the incidence of adverse events. We performed pairwise and network meta-analysis for all treatments, and used Grading of Recommendations, Assessment, Development, and Evaluation criteria to appraise the quality of evidence. RESULTS: All treatments except mechanical lithotripsy significantly outperformed sphincterotomy in terms of stone removal rate (risk ratio [RR], 1.03-1.29). SOC was superior to other adjunctive interventions (vs balloon sphincteroplasty [RR, 1.24; 95% CIs, 1.07-1.45], vs S+EPLBD [RR, 1.23; range, 1.06-1.42] and vs mechanical lithotripsy [RR, 1.34; range, 1.14-1.58]). Cholangioscopy ranked the highest in increasing the success rate of stone removal (surface under the cumulative ranking [SUCRA] score, 0.99) followed by S+EPLBD (SUCRA score, 0.68). SOC and S+EPLBD outperformed the other modalities when only studies reporting on stones greater than 15 mm were taken into consideration (SUCRA scores, 0.97 and 0.71, respectively). None of the assessed interventions was significantly different in terms of adverse event rate compared with endoscopic sphincterotomy or with other treatments. Post-ERCP pancreatitis and bleeding were the most frequent adverse events. CONCLUSIONS: Among patients with large bile stones, cholangioscopy represents the most effective method, in particular in patients with larger (>15 mm) stones, whereas S+EPLBD could represent a less expensive and more widely available alternative.

Endoscopic Ultrasound-guided Radiofrequency Ablation Versus Surgical Resection for Treatment of Pancreatic Insulinoma.

BACKGROUND & AIMS: Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is emerging as a safe and effective treatment for pancreatic neuroendocrine tumors. We aimed to compare EUS-RFA and surgical resection for the treatment of pancreatic insulinoma (PI). METHODS: Patients with sporadic PI who underwent EUS-RFA at 23 centers or surgical resection at 8 high-volume pancreatic surgery institutions between 2014 and 2022 were retrospectively identified and outcomes compared using a propensity-matching analysis. Primary outcome was safety. Secondary outcomes were clinical efficacy, hospital stay, and recurrence rate after EUS-RFA. RESULTS: Using propensity score matching, 89 patients were allocated in each group (1:1), and were evenly distributed in terms of age, sex, Charlson comorbidity index, American Society of Anesthesiologists score, body mass index, distance between lesion and main pancreatic duct, lesion site, size, and grade. Adverse event (AE) rate was 18.0% and 61.8% after EUS-RFA and surgery, respectively (P < .001). No severe AEs were observed in the EUS-RFA group compared with 15.7% after surgery (P < .0001). Clinical efficacy was 100% after surgery and 95.5% after EUS-RFA (P = .160). However, the mean duration of follow-up time was shorter in the EUS-RFA group (median, 23 months; interquartile range, 14-31 months vs 37 months; interquartile range, 17.5-67 months in the surgical group; P < .0001). Hospital stay was significantly longer in the surgical group (11.1 ± 9.7 vs 3.0 ± 2.5 days in the EUS-RFA group; P < .0001). Fifteen lesions (16.9%) recurred after EUS-RFA and underwent a successful repeat EUS-RFA (11 patients) or surgical resection (4 patients). CONCLUSION: EUS-RFA is safer than surgery and highly effective for the treatment of PI. If confirmed in a randomized study, EUS-RFA treatment can become first-line therapy for sporadic PI.

Endoscopic ultrasound fine-needle biopsy to assess DAXX/ATRX expression and alternative lengthening of telomeres status in non-functional pancreatic neuroendocrine tumors.

BACKGROUND/OBJECTIVES: Death domain-associated protein (DAXX) and/or α-thalassemia/mental retardation X-linked (ATRX) chromatin remodeling genes mutations and alternative lengthening of telomeres (ALT) activation are associated with more aggressive behavior of non-functional pancreatic neuroendocrine tumors (NF-PanNETs). We aimed to evaluate the reliability of such markers on endoscopic-ultrasound fine-needle biopsy (EUS-FNB) specimens. METHODS: Patients who underwent EUS-FNB and subsequent surgical resection for PanNETs between January 2017 and December 2019 were retrospectively identified. Immunohistochemistry (IHC) to evaluate DAXX/ATRX expression and fluorescence in situ hybridization (FISH) for ALT status were performed. Primary outcome was the concordance rate of markers expression between EUS-FNB and surgical specimens. Secondary aims were association between markers and lesion aggressiveness, their diagnostic performance in predicting aggressiveness, and agreement of preoperative and post-surgical Ki67-based grading. RESULTS: Forty-one NF-PanNETs (mean diameter 36.1 ± 26.5 mm) were included. Twenty-four showed features of lesion aggressiveness. Concordance of expressions of DAXX, ATRX, and ALT status between EUS-FNB and surgical specimens were 95.1% (κ = 0.828; p < 0.001), 92.7% (κ = 0.626; p < 0.001), and 100% (κ = 1; p < 0.001), respectively. DAXX/ATRX loss and ALT-positivity were significantly (p < 0.05) associated with metastatic lymphnodes and lymphovascular invasion. The combination of all tumor markers (DAXX/ATRX loss + ALT-positivity + grade 2) reached an accuracy of 73.2% (95%CI 57.1-85.8) in identifying aggressive lesions. Pre- and post-operative ki-67-based grading was concordant in 80.5% of cases (k = 0.573; p < 0.001). CONCLUSION: DAXX/ATRX expression and ALT status can be accurately evaluated in a preoperative setting on EUS-FNB samples, potentially improving the identification of patients with increased risk and poorer prognosis.

Comparative diagnostic performance of different techniques for EUS-guided fine-needle biopsy sampling of solid pancreatic masses: a network meta-analysis.

BACKGROUND AND AIMS: Evidence is limited on the comparative diagnostic performance of tissue sampling techniques for EUS-guided fine-needle biopsy sampling of pancreatic masses. We performed a systematic review with network meta-analysis to compare these techniques. METHODS: Rates of sample adequacy, blood contamination, and tissue integrity using fine-needle biopsy sampling needles were evaluated. Direct and indirect comparisons were performed among the slow-pull, dry-suction, modified wet-suction, or no-suction techniques. Results are expressed as risk ratio (RR) and 95% confidence interval (CI). RESULTS: Overall, 9 randomized controlled trials (756 patients) were identified. On network meta-analysis, the no-suction technique was significantly inferior to the other techniques (RR, .85 [95% CI, .78-.92] vs slow pull; RR, .85 [95% CI, .78-.92] vs dry suction; RR, .83 [95% CI, .76-.90] vs modified wet suction) in terms of sample adequacy. Consequently, modified wet suction was shown to be the best technique (surface under the cumulative ranking curve score, .90), with the no-suction technique showing poorer performance in terms of sample adequacy (surface under the cumulative ranking curve score, .14). Dry suction was associated with significantly higher rates of blood contamination as compared with the slow-pull technique (RR, 1.44; 95% CI, 1.15-1.80), whereas no suction led to less blood contamination of samples in comparison with other techniques (RR, .71 [95% CI, .52-.97] vs slow pull; RR, .49 [95% CI, .36-.66] vs dry suction; RR, .57 [95% CI, .40-.81] vs modified wet suction). The modified wet-suction technique significantly outperformed dry suction in terms of tissue integrity of the sample (RR, 1.36; 95% CI, 1.06-1.75). CONCLUSIONS: Modified wet suction seemed to provide high rates of integrity and adequate samples, albeit with high blood contamination. The no-suction technique performed significantly worse than other sampling strategies.

Endoscopic ultrasound-guided fine-needle biopsy with or without macroscopic on-site evaluation: a randomized controlled noninferiority trial.

BACKGROUND : The advantage of using the macroscopic on-site evaluation (MOSE) technique during endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) performed with 22G Franseen needles has not been investigated. We aimed to compare EUS-FNB with MOSE vs. EUS-FNB performed with three needle passes. METHODS : This randomized trial involved 10 Italian referral centers. Consecutive patients referred for EUS-FNB of pancreatic or nonpancreatic solid lesions were included in the study and randomized to the two groups. MOSE was performed by gross visualization of the collected material by the endoscopists and considered adequate when a white/yellowish aggregate core longer than 10 mm was retrieved. The primary outcome was diagnostic accuracy. Secondary outcomes were specimen adequacy, number of needle passes, and safety. RESULTS : 370 patients with 234 pancreatic lesions (63.2 %) and 136 nonpancreatic lesions (36.8 %) were randomized (190 EUS-FNB with MOSE and 180 with standard EUS-FNB). No statistically significant differences were found between EUS-FNB with MOSE and conventional EUS-FNB in terms of diagnostic accuracy (90.0 % [95 %CI 84.8 %-93.9 %] vs. 87.8 % [95 %CI 82.1 %-92.2 %]; P = 0.49), sample adequacy (93.1 % [95 %CI 88.6 %-96.3 %] vs. 95.5 % [95 %CI 91.4 %-98 %]; P = 0.31), and rate of adverse events (2.6 % vs. 1.1 %; P = 0.28). The median number of passes was significantly lower in the EUS-FNB with MOSE group (1 vs. 3; P < 0.001). CONCLUSIONS : The accuracy of EUS-FNB with MOSE is noninferior to that of EUS-FNB with three needle passes. MOSE reliably assesses sample adequacy and reduces the number of needle passes required to obtain the diagnosis with a 22G Franseen needle.

Wet-suction versus slow-pull technique for endoscopic ultrasound-guided fine-needle biopsy: a multicenter, randomized, crossover trial.

BACKGROUND : It is unknown whether there is an advantage to using the wet-suction or slow-pull technique during endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) with new-generation needles. We aimed to compare the performance of each technique in EUS-FNB. METHODS: This was a multicenter, randomized, single-blind, crossover trial including patients with solid lesions of ≥ 1 cm. Four needle passes with 22 G fork-tip or Franseen-type needles were performed, alternating the wet-suction and slow-pull techniques in a randomized order. The primary outcome was the histological yield (samples containing an intact piece of tissue of at least 550 µm). Secondary end points were sample quality (tissue integrity and blood contamination), diagnostic accuracy, and adequate tumor fraction. RESULTS: Overall, 210 patients with 146 pancreatic and 64 nonpancreatic lesions were analyzed. A tissue core was retrieved in 150 (71.4 %) and 129 (61.4 %) cases using the wet-suction and the slow-pull techniques, respectively (P = 0.03). The mean tissue integrity score was higher using wet suction (P = 0.02), as was the blood contamination of samples (P < 0.001). In the two subgroups of pancreatic and nonpancreatic lesions, tissue core rate and tissue integrity score were not statistically different using the two techniques, but blood contamination was higher with wet suction. Diagnostic accuracy and tumor fraction did not differ between the two techniques. CONCLUSION: Overall, the wet-suction technique in EUS-FNB resulted in a higher tissue core procurement rate compared with the slow-pull method. Diagnostic accuracy and the rate of samples with adequate tumor fraction were similar between the two techniques.

EUS-guided coil and glue injection versus endoscopic glue injection for gastric varices: International multicentre propensity-matched analysis.

BACKGROUND: Gastric varices (GVs) are conventionally managed with endoscopic cyanoacrylate (E-CYA) glue injection. Endoscopic ultrasound (EUS)-guided therapy using combination of coils and CYA glue (EUS-CG) is a relatively recent modality. There is limited data comparing the two techniques. METHODOLOGY: This international multicentre study included patients with GV undergoing endotherapy from two Indian and two Italian tertiary care centres. Patients undergoing EUS-CG were compared with propensity-matched E-CYA cases from a cohort of 218 patients. Procedural details such as amount of glue, number of coils used, number of sessions required for obliteration, bleeding after index procedure rates and need for re-intervention were noted. RESULTS: Of 276 patients, 58 (male 42, 72.4%; mean age-44.3 ± 12.1 years) underwent EUS-CG and were compared with 118 propensity-matched cases of E-CYA. In the EUS-CG arm, complete obliteration at 4 weeks was noted in 54 (93.1%) cases. Compared to the E-CYA cohort, EUS-CG arm showed significantly lower number of session (1.0 vs. 1.5; p < 0.0001) requirement, lower subsequent-bleeding episodes (13.8% vs. 39.1%; p < 0.0001) and lower re-intervention (12.1% vs. 50.4%; p < 0.001) rates. On multivariable regression analysis, size of the varix (aOR-1.17; CI 1.08-1.26) and technique of therapy (aOR-14.71; CI 4.32-50.0) were significant predictors of re-bleeding. A maximum GV size >17.5 mm had a 69% predictive accuracy for need for re-intervention. CONCLUSION: Endoscopic ultrasound-guided therapy of GV using coil and CYA glue is a safe technique with better efficacy and lower re-bleeding rates on follow-up compared to the conventional endoscopic CYA therapy.

Repeated endoscopic ultrasound-guided fine-needle biopsy of solid pancreatic lesions after previous nondiagnostic or inconclusive sampling.

OBJECTIVES: Repeated endoscopic ultrasound (EUS)-guided tissue acquisition represents the standard practice for solid pancreatic lesions after previous nondiagnostic or inconclusive results. Since data are lacking, we aimed to evaluate the diagnostic performance of repeated EUS fine-needle biopsy (rEUS-FNB) in this setting. The primary outcome was diagnostic accuracy; sample adequacy, sensitivity, specificity, and safety were secondary outcomes. METHODS: Consecutive patients undergoing rEUS-FNB for solid pancreatic lesions at 23 Italian centers from 2019 to 2021 were retrieved. Pathology on the surgical specimen, malignant histology together with ≥6-month follow-up, and benign pathology together with ≥12-month follow-up were adopted as gold standards. RESULTS: Among 462 patients, 56.5% were male, with a median age of 68 (59-75) years, malignancy prevalence 77.0%. Tumor size was 26 (20-35) mm. Second-generation FNB needles were used in 89.6% cases. Diagnostic accuracy, sensitivity, and specificity of rEUS-FNB were 89.2%, 91.4%, and 81.7%, respectively (19 false-negative and 12 false-positive results). On multivariate analysis, rEUS-FNB performed at high-volume centers (odds ratio [OR] 2.12; 95% confidence interval [CI] 1.10-3.17; P = 0.03) and tumor size (OR 1.03; 95% CI 1.00-1.06; P = 0.05) were independently related to diagnostic accuracy. Sample adequacy was 94.2%. Use of second-generation FNB needles (OR 5.42; 95% CI 2.30-12.77; P < 0.001) and tumor size >23 mm (OR 3.04; 95% CI 1.31-7.06; P = 0.009) were independently related to sample adequacy. CONCLUSION: Repeated EUS-FNB allowed optimal diagnostic performance after nondiagnostic or inconclusive results. Patients' referral to high-volume centers improved diagnostic accuracy. The use of second-generation FNB needles significantly improved sample adequacy over standard EUS-FNB needles.

Efficacy and Safety of Endoscopic Ultrasound-Guided Radiofrequency Ablation for Pancreatic Neuroendocrine Tumors: A Systematic Review and Metanalysis.

Introduction: The development of dedicated endoscopes and the technical evolution of endoscopic ultrasound (EUS) have allowed a direct approach to pancreatic neoplastic lesions both for diagnosis and treatment. Among the more promising targets are pancreatic neuroendocrine tumors (Pan-NETs). Aim: to describe the evolution of endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) with particular attention to the treatment of PanNETs, focusing on safety and clinical efficacy of the technique. Methods: MEDLINE, Scopus, and Cochrane Library databases were searched for studies reporting about EUS-RFA for the treatment of PanNETs. Studies with outcomes of interest were selected and results were reported to describe clinical success, complications, fol-low-ups, and electrodes used. Clinical success was defined as the disappearance of clinical symp-toms for functional (F-) PanNETs and as complete ablation per nonfunctional (NF)-PanNETs. The pooled data were analyzed by a random-effects model. Results: Nineteen studies were selected, including 183 patients (82 males, 44.8%) with 196 lesions (101 F-PanNETs and 95 NF-PanNETs). Pooled estimates for the overall AE rates for the clinical efficacy were 17.8% (95% CI 9.1-26.4%) and 95.1% (95% CI 91.2-98.9%) for F-PanNETs and 24.6% (95% CI 7.4-41.8%) and 93.4% (95% CI 88.4-98.4%) for NF-PanNETs. Conclusions: EUS-RFA appears to be a mini-invasive technique with a good safety and efficacy profile for the treatment of F- and NF-PanNETs. EUS-RFA could be of-fered as possible alternative to surgery for the treatment of low-grade NF- or F-PanNETs, especially for those patients that are not eligible or are at high-risk for surgery.

Endoscopic Ultrasound-guided Fine-needle Biopsy With or Without Rapid On-site Evaluation for Diagnosis of Solid Pancreatic Lesions: A Randomized Controlled Non-Inferiority Trial.

BACKGROUND AND AIMS: The benefit of rapid on-site evaluation (ROSE) on the diagnostic accuracy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) has never been evaluated in a randomized study. This trial aimed to test the hypothesis that in solid pancreatic lesions (SPLs), diagnostic accuracy of EUS-FNB without ROSE was not inferior to that of EUS-FNB with ROSE. METHODS: A noninferiority study (noninferiority margin, 5%) was conducted at 14 centers in 8 countries. Patients with SPLs requiring tissue sampling were randomly assigned (1:1) to undergo EUS-FNB with or without ROSE using new-generation FNB needles. The touch-imprint cytology technique was used to perform ROSE. The primary endpoint was diagnostic accuracy, and secondary endpoints were safety, tissue core procurement, specimen quality, and sampling procedural time. RESULTS: Eight hundred patients were randomized over an 18-month period, and 771 were analyzed (385 with ROSE and 386 without). Comparable diagnostic accuracies were obtained in both arms (96.4% with ROSE and 97.4% without ROSE, P = .396). Noninferiority of EUS-FNB without ROSE was confirmed with an absolute risk difference of 1.0% (1-sided 90% confidence interval, -1.1% to 3.1%; noninferiority P < .001). Safety and sample quality of histologic specimens were similar in both groups. A significantly higher tissue core rate was obtained by EUS-FNB without ROSE (70.7% vs. 78.0%, P = .021), with a significantly shorter mean sampling procedural time (17.9 ± 8.8 vs 11.7 ± 6.0 minutes, P < .0001). CONCLUSIONS: EUS-FNB demonstrated high diagnostic accuracy in evaluating SPLs independently on execution of ROSE. When new-generation FNB needles are used, ROSE should not be routinely recommended. (ClinicalTrial.gov number NCT03322592.).

Reliability of grading preoperative pancreatic neuroendocrine tumors on EUS specimens: a systematic review with meta-analysis of aggregate and individual data.

BACKGROUND AND AIMS: Therapy and prognosis of pancreatic neuroendocrine tumors (PanNETs) are strictly related to the Ki-67 index, which defines tumor grading. The criterion standard for the assessment of grading of PanNETs is EUS-guided FNA (EUS-FBAFNA) or EUS-guided fine-needle biopsy sampling (EUS-FNB). Because data on diagnostic accuracy of EUS-FNA and EUS-FNB are heterogeneous, we aimed to analyze the variability in concordance between EUS grading and surgical grading. METHODS: The MEDLINE, SCOPUS, and EMBASE databases were searched until November 2021 to identify studies reporting the concordance rate between EUS grading and surgical grading. The study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Pooled events were calculated using a random-effects model and expressed in terms of pooled prevalence rates. A multivariate meta-regression was performed to find possible sources of heterogeneity. Where available, individual data were analyzed. RESULTS: Twenty-six studies with 864 patients undergone EUS-FNA or EUS-FNB and surgical resection for PanNETs were included. The pooled estimate rate for the overall concordance of EUS grading and surgical grading was 80.3% (95% confidence interval, 75.6-85.1). Undergrading (EUS grading < surgical grading) was significantly more frequent with respect to overgrading (14.7% vs 3.5%, P < .001). Individual data analysis showed that among nonconcordant patients, the median Ki-67 difference was 3% (interquartile range, 2-6.15). The type of World Health Organization classification adopted and the median lesion diameter were significantly associated with heterogeneity at meta-regression. CONCLUSIONS: EUS is an accurate technique in defining grading in patients with PanNETs, but a margin of error still exists, which should be the focus of future studies to minimize the risk of over- and/or undertreatment.

Comparative diagnostic performance of end-cutting fine-needle biopsy needles for EUS tissue sampling of solid pancreatic masses: a network meta-analysis.

BACKGROUND AND AIMS: Evidence is limited on the comparative diagnostic performance of newer end-cutting fine-needle biopsy (FNB) needles for tissue sampling of pancreatic masses. We performed a systematic review with network meta-analysis to compare the diagnostic accuracy of available FNB needles for sampling of solid pancreatic lesions. METHODS: A systematic literature review (Medline and Cochrane Database) was conducted for studies evaluating the accuracy of newer FNB needles in adults undergoing EUS-guided sampling of solid pancreatic masses. The primary outcome was diagnostic accuracy. Secondary outcomes were sample adequacy, diagnostic sensitivity, specificity, and adverse event rate. We performed pairwise and network meta-analyses and appraised the quality of evidence using Grading of Recommendations Assessment, Development and Evaluation methodology. RESULTS: Overall, 16 RCTs (1934 patients) were identified. On network meta-analysis, Franseen needles (Acquire; Boston Scientific, Marlborough, Mass, USA) significantly outperformed reverse-bevel needles (risk ratio [RR], 1.21 [95% confidence interval {CI}, 1.05-1.40] for accuracy and 1.31 [95% CI, 1.05-1.22] for adequacy) and FNA needles (RR, 1.21 [95% CI, 1.01-1.25] for accuracy and 1.07 [95% CI, 1.02-1.13] for adequacy). Likewise, the Fork-tip needle (SharkCore; Medtronic, Dublin, Ireland) was significantly superior to the reverse-bevel needle (RR, 1.17 [95% CI, 1.03-1.33] for accuracy and 1.09 [95% CI, 1.02-1.16] for adequacy) and to the FNA needle (RR, 1.09 [95% CI, 1.01-1.19] for accuracy and 1.03 [95% CI, 1.01-1.07] for adequacy). Other comparisons did not achieve statistical significance. As a consequence, Franseen (surface under the cumulative ranking score, .89 for accuracy and .94 for adequacy) and Fork-tip needles (surface under the cumulative ranking score, .76 for accuracy and .73 for adequacy) ranked as the 2 highest-performing FNB needles. When considering different needle sizes, 25-gauge Franseen and 25-gauge Fork-tip needles were not superior to 22-gauge reverse-bevel needles (RR, 1.18 [95% CI, .96-1.46] and 1.04 [95% CI, .62-1.52]). None of the tested needles was significantly superior to the other FNB devices or to FNA needles when rapid onsite cytologic evaluation was available. CONCLUSIONS: Franseen and Fork-tip needles, particularly 22-gauge size, showed the highest performance for tissue sampling of pancreatic masses, with low confidence in estimates.

Definition of a hospital volume threshold to optimize outcomes after drainage of pancreatic fluid collections with lumen-apposing metal stents: a nationwide cohort study.

BACKGROUND AND AIMS: There is increasing interest in expanding the use of lumen-apposing metal stents (LAMSs) in patients with pancreatic fluid collections (PFCs). The aim of this study was to determine whether there is a hospital volume threshold for which patient outcomes could be optimized. METHODS: Data from a large multicenter series of patients with PFCs treated with LAMSs were retrieved. Rate of adverse events (AEs) was the primary outcome. Multivariable models with restricted cubic splines were used to identify a hospital volume threshold by plotting hospital volume against the log odds ratio (OR) of AE rate. Propensity score matching was applied to obtain 2 well-balanced groups according to hospital volume, and univariate/multivariate logistic regression analysis was performed to identify significant predictors of AEs. RESULTS: Overall, 516 patients were included. Increasing hospital volume was associated with a reduced AE rate (P = .03), and the likelihood of experiencing an AE declined as hospital volume increased up to 15 cases. After propensity score matching, 175 patients in the high-volume (>15 cases) and 132 in the low-volume hospital group were compared. Overall, 41 AEs were observed (13.3%), of which 14 (8%) and 27 (20.4%) occurred at high-volume and low-volume centers, respectively (P = .001). Severe and fatal events were observed more frequently in low-volume centers (6% vs 1.7% and 2.2% vs 0%, respectively; P = .05). In multivariate analysis, main pancreatic duct injury (OR, 2.62; 95% confidence interval [CI], 1.26-4.67; P = .02), presence of abnormal vessels (OR, 2.93; 95% CI, 1.41-5.02; P = .006), and institutional experience (OR, 2.95; 95% CI, 1.48-5.90; P = .002) were significant predictors of AEs. CONCLUSIONS: With 15 procedures representing the minimum number of cases associated with the lowest risk for postprocedural AEs, hospital volume is associated with improved outcomes. (Clinical trial registration number: NCT03903523.).

Safety and efficacy of a novel electrocautery-enhanced lumen-apposing metal stent in interventional EUS procedures (with video).

BACKGROUND AND AIMS: Electrocautery-tip lumen-apposing metal stents (EC-LAMSs) have extended the indications of therapeutic EUS. We aimed to retrospectively evaluate safety and technical and clinical success of a newly developed EC-LAMS, the Hot-Spaxus (Taewoong Medical Co, Gimpo, Korea), for various EUS-guided procedures. METHODS: We included and retrospectively analyzed consecutive patients at 8 tertiary care referral centers who had undergone EUS interventional procedures using the Hot-Spaxus between October 2018 and February 2021. RESULTS: Of 58 included patients (male-to-female, 36:22; mean age, 63.5 ± 14.9 years), 29 had undergone pancreatic fluid collection drainage (50%), 22 (37.9%) biliary drainage for malignant distal obstruction, 3 (5.1%) gallbladder drainage for acute cholecystitis, 3 gastroenteroanastomoses, and 1 (1.7%) pelvic collection drainage. Technical success was achieved in 54 of 58 patients (93.1%) and clinical success in all 58. Adverse events occurred in 6 patients (11.1%): 2 early (3.7%), 1 late (1.8%), and 3 long term (5.6%). The outcomes were similar to those observed in a control group of patients treated with the Hot-Axios (Boston Scientific, Marlborough, Mass, USA), the other available EC-LAMS. CONCLUSIONS: Our study showed that the novel EC-LAMS has high technical and clinical success rates for various interventional EUS indications. Future multicenter prospective studies will better clarify the role of this new EC-LAMS for different indications.