Objective: Several studies compared endoscopic ultrasound biliary drainage (EUS-BD) to endoscopic retrograde cholangiopancreatography (ERCP) with stenting as first-line intervention in patients with distal malignant biliary obstruction (DMBO). We aimed to assess the pooled efficacy and safety of these two approaches.

Comprehensive database search was performed to identify randomized controlled trials reporting the outcomes of EUS-BD compared to ERCP for primary biliary drainage in patients with DMBO. The primary outcome was technical success. Secondary outcomes were clinical success, adverse events (AEs), severe AEs rate, mean procedure time, 1-year stent patency, and overall survival. Relative risk with 95% confidence interval (CI) were calculated using fixed-effect model. Heterogeneity was assessed using I2. Sub-group analysis was planned to compare studies that use self-expandable metal stents (SEMS) and lumen-apposing metal stents (LAMS) for EUS-BD.

Five studies involving 519 patients were included. Pooled technical success rate was significantly higher in patients who underwent EUS-BD compared to ERCP (RR 1.09; 95% C.I. 1.03 – 1.16; P = 0.004); Sensitivity analysis suggested that small studies (<100 patients), single-center studies, and studies published before 2020 showed lower technical success rate in the EU-BD treatment arms; common bile duct diameter ≥16 mm was related to higher technical success rate in the EUS-BD treatment arms. Pooled clinical success was similar in the two treatment arms (RR 1.01; 95% C.I. 0.95 – 1.08; P = 0.68). Pooled 1-year stent patency was significantly higher in EUS-BD group (RR 1.14; 95% C.I. 1.05 – 1.25, P = 0.003), with significantly lower reintervention (RR 0.58; 95% C.I. 0.38 – 0.88; P = 0.012). A trend towards a lower pooled incidence of AEs (RR 0.69; 95% C.I. 0.47 – 1.01; P = 0.06) and severe AEs (RR 0.97; 95% C.I. 0.14 – 6.82; P = 0.07) was observed in EUS-BD group. Procedure time was significantly lower in EUS-BD treatment arms (standardized mean difference -2.36; 95% C.I. -2.68 - -2.05; P < 0.001). No difference in mean overall survival was found (standardized mean difference 0.58; 95% C.I. 0.37 – 0.78; P < 0.001). Subgroup analysis comparing SEMS and LAMS for EUS-BD showed that the three studies conducted with SEMS for EUS-BD accounted for the higher 1-year stent patency rate and for the reduced need for reintervention and incidence of AEs, while the two studies conducted with LAMS accounted for the improved technical success rate and reduced mean procedure time.

EUS-BD showed a higher pooled technical success rate and 1-year stent patency rate compared to ERCP stenting as first-line approach in patients with DMBO. No difference in terms of clinical success rate and incidence of AEs and severe AEs was observed. The use of LAMS seems to improve EUS-BD technical success rate and reduce incidence of AEs, while use of SEMS for EUS-BD improves the patency and reduces the need for biliary reintervention.

Endoscopic ultrasonography (EUS) combined with the development of specifically designed stents has significantly increased the indications for EUS guided interventional procedure as in case of patients needing the positioning of a lumen apposing metal stent (LAMS) to create an anastomosis between the stomach and the jejunum (EUS-GE). Moreover, in patients with altered anatomy due to previous surgery, such as Roux-en-Y reconstructions and bariatric surgery, further type of EUS-guided anastomosis permit to perform endoscopic retrograde cholagiopancreatography (ERCP) or to treat afferent limb syndrome, such as gastrogastrostomy (EUS-GG) or jejunojejunostomy (EUS-JJ). The aim of this study is to evaluate performances and safety of EUS-guided anastomosis (EUS-GE, EUS-GG and EUS-JJ) for any indication in a large multicenter study.

This retrospective multicenter study included all consecutive patients treated with EUS-guided anastomoses (EUS-GE, EUS-GG and EUS-JJ) from January 2016 to March 2023 at eleven Italian tertiary centers. Indications for EUS-guided anastomosis were gastric outlet obstruction (GOO), afferent lymb syndrome or patients with altered anatomy and needs for ERCP. The main outcomes of interest were technical success and clinical success. Clinical success was defined as ability and type (liquid, creamy/soft or solid) of oral intake for EUS-GE, capability to perform ERCP for EUS-GG and resolution of jaundice for EUS-JJ. Secondary endpoints included rate of adverse events, LAMS patency and need for re-interventions.

204 patients (mean [±SD] age 64,08 [±13,97] years; 50% males) were included. EUS-guided anastomosis were performed for GOO in 139 cases (68,1%), for bilio-enteric anastomotic strictures or lithiasis in altered anatomy needing jejunal access in 44 (21,6%) cases, for afferent limb syndrome in 14 cases (6,9%) and for performing ERCP in altered anatomy in case of EUS-GG in 7 patients (3,4%). EUS-GE were performed in 153 patients (75%), EUS-JJ in 44 cases (21,6%) and EUS-GG in 7 (3,4%). The diameter of the LAMS were 15 mm in 57,9% of cases, while 20 and 16 mm were used in 38,6% and 3,5% of cases, respectively. Overall, technical success was 94,6% (CI 95% 90.6-96.96%) and clinical success was 93,3% (CI 95% 88.82-96.02%). The total rate of AEs was 11,9%. Ten (7,5%) patients developed recurrence of GOO symptoms with a median time of 56 days (CI 95% 11,47-415,78). The median follow-up was 85 days (CI 95%, 69-115), and 51 patients died (25%) with a median time to death of 67 days (41,05 to 136,96).

EUS-guided anastomosis for connecting two sites of the upper GI tracts (EUS-GE, EUS-GG and EUS-JJ) are technically feasible procedures both in malignant and benign diseases, showing a high clinical success. The rate of AEs permits to consider EUS anastomosis a safe procedure in expert hands.

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). Most published studies investigated these biomarkers on surgical specimens. 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. Patients with metastatic disease at diagnosis, mixed types (e.g., mixed neuroendocrine-acinar/adenocarcinoma) or neuroendocrine carcinomas, predominantly cystic lesions (more than 50% of the volume), systemic anticancer therapy before resection, presence of multiples lesions, genetic syndromes associated with PanNETs (i.e., multiple endocrine neoplasia type 1 syndrome, von-Hippel Lindau syndrome, etc.), and functional PanNETs were excluded. 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. Tumor aggressiveness was defined as the presence of metastatic lymph node and/or lymphovascular invasion and/or perineural invasion and/or grade 2 on surgical specimen and/or local recurrence/appearance of lymph node/distant metastases on imaging during follow-up. Results Forty-one patients (41.5% males, 53  11.0 years) with NF-PanNETs (mean diameter 36.126.5mm) were included. Twenty-four (58.5%) lesions presented with at least one aggressive feature. Loss of expression of DAXX/ATRX and positive ALT status were observed in 12 (29.3%) and in ten (24.4%) lesions, respectively. 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, Table 1). 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.

BACKGROUND Despite the increasing diffusion of non-invasive tests for the diagnosis of liver diseases, histological assessment through liver biopsy (LB) is still often mandatory especially in unclear cases. Actually, percutaneous approach (PC-LB) is the gold standard. Nowadays, endoscopic ultrasound-guided liver biopsy (EUS-LB) has emerged as an established method to achieve liver tissue sampling. EUS-LB has several advantages such as: sampling of both liver lobes, it allows to obtain liver tissue sampling in case of ascites and to avoid damage to nearby organs and vessels.

We performed a systematic review with meta-analysis (MA) to evaluate the diagnostic outcomes and safety for liver tissue acquisition of PC-LB and EUS-LB in patients with liver diseases and focal liver lesions. Studies that compare diagnostic outcomes of PC-LB and EUS-LB were identified through literature search using MEDLINE, Embase and Scopus until September 2023. MA was performed according to a frequentist approach. For technical success and accuracy, the untransformed proportions were estimated by the DerSimonian and Laird random-effects model.

11 studies recruiting 1.389 patients of which 724 underwent PC-LB and 665 underwent EUS-L were included in MA. Overall, pooled diagnostic adequacy showed an OR 2.062 (95% CI: 0.360 - 11976 I2 = 71.4%, P=0.002) when comparing PC-LB to EUS-LB. Pooled accuracy between the two procedures was OR 3.071 (95% CI: 0.166 – 56.644 I2 = 64.47%, P=0.06). Pooled rate of overall adverse events was slightly higher in PC-LB compared to EUS-LB, OR: 1.297 (95% IC: 0.484 – 3.475 644 I2 = 35.34 %, P=0.146. Overall no differences between the two procedures were observed I term of total length specimen and in term of complete portal tract.

In conclusion, out meta-analysis do not show significant differences between PC-LB and EUS-LB in terms of adequacy, technical success and accuracy, albeit EUS-LB is slightly safer than PC-LB.