Establishing the optimal number of passes during EUS-FNB for diagnosis of pancreatic solid lesions: Prospective multicenter study.

Background and study aims The optimal number of needle passes during endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) is not yet established. We aimed to perform a per-pass analysis of the diagnostic accuracy of EUS-FNB of solid pancreatic lesions using a 22G Franseen needle. Patients and methods Consecutive patients with solid pancreatic lesions referred to 11 Italian centers were prospectively enrolled. Three needle passes were performed; specimens were collected after each pass and processed individually as standard histology following macroscopic on-site evaluation (MOSE) by the endoscopist. The primary endpoint was diagnostic accuracy of each sequential pass. Final diagnosis was established based on surgical pathology or a clinical course of at least 6 months. Secondary endpoints were specimen adequacy, MOSE reliability, factors impacting diagnostic accuracy, and procedure-related adverse events. Results A total of 504 samples from 168 patients were evaluated. Diagnostic accuracy was 90.5% (85.0%-94.1%) after one pass and 97.6% (94.1%-99.3%) after two passes ( P =0.01). Similarly, diagnostic sensitivity and sample adequacy were significantly higher adding the second needle pass (90.2%, 84.6%-94.3% vs 97.5%, 93.8%-99.3%, P =0.009 and 91.1%, 85.7%-94.9% vs 98.2%, 95.8%-99.3%, P =0.009, one pass vs two passes, respectively). Accuracy, sensitivity, and adequacy remained the same after the third pass. The concordance between MOSE and histological evaluation was 89.9%. The number of passes was the only factor associated with accuracy. One case of mild acute pancreatitis (0.6%) was managed conservatively. Conclusions At least two passes should be performed for the diagnosis of solid pancreatic lesions. MOSE is a reliable tool to predict the histological adequacy of specimens.

Endoscopic Ultrasound-Guided Gastroenterostomy versus Enteral Stenting for Malignant Gastric Outlet Obstruction: A Retrospective Propensity Score-Matched Study.

BACKGROUND: Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) using lumen apposing metal stent has emerged as a minimally invasive treatment for the management of malignant gastric outlet obstruction (mGOO). We aimed to compare EUS-GE with enteral stenting (ES) for the treatment of mGOO. METHODS: Patients who underwent EUS-GE or ES for mGOO between June 2017 and June 2023 at two Italian centers were retrospectively identified. The primary outcome was stent dysfunction. Secondary outcomes included technical success, clinical failure, safety, and hospital length of stay. A propensity score-matching analysis was performed using multiple covariates. RESULTS: Overall, 198 patients were included (66 EUS-GE and 132 ES). The stent dysfunction rate was 3.1% and 16.9% following EUS-GE and ES, respectively (p = 0.004). Using propensity score-matching, 45 patients were allocated to each group. The technical success rate was 100% for both groups. Stent dysfunction was higher in the ES group compared with the EUS-GE group (20% versus 4.4%, respectively; p = 0.022) without differences in clinical efficacy (p = 0.266) and safety (p = 0.085). A significantly shorter hospital stay was associated with EUS-GE compared with ES (7.5 ± 4.9 days vs. 12.5 ± 13.0 days, respectively; p = 0.018). Kaplan-Meier analyses confirmed a higher stent dysfunction-free survival rate after EUS-GE compared with ES (log-rank test; p = 0.05). CONCLUSION: EUS-GE offers lower rates of stent dysfunction, longer stent patency, and shorter hospital stay compared with ES.

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.

Outcomes of a 3-Year Prospective Surveillance in Individuals at High Risk of Pancreatic Cancer.

INTRODUCTION: Pancreatic cancer (PC) surveillance of high-risk individuals (HRI) is becoming more common worldwide, aiming at anticipating PC diagnosis at a preclinical stage. In 2015, the Italian Registry of Families at Risk of Pancreatic Cancer was created. We aimed to assess the prevalence and incidence of pancreatic findings, oncological outcomes, and harms 7 years after the Italian Registry of Families at Risk of Pancreatic Cancer inception, focusing on individuals with at least a 3-year follow-up or developing events before. METHODS: HRI (subjects with a family history or mutation carriers with/without a family history were enrolled in 18 centers). They underwent annual magnetic resonance with cholangiopancreatography or endoscopic ultrasound (NCT04095195). RESULTS: During the study period (June 2015-September 2022), 679 individuals were enrolled. Of these, 524 (77.2%) underwent at least baseline imaging, and 156 (29.8%) with at least a 3-year follow-up or pancreatic malignancy/premalignancy-related events, and represented the study population. The median age was 51 (interquartile range 16) years. Familial PC cases accounted for 81.4% of HRI and individuals with pathogenic variant for 18.6%. Malignant (n = 8) and premalignant (1 PanIN3) lesions were found in 9 individuals. Five of these 8 cases occurred in pathogenic variant carriers, 4 in familial PC cases (2 tested negative at germline testing and 2 others were not tested). Three of the 8 PC were stage I. Five of the 8 PC were resectable, 3 Stage I, all advanced cases being prevalent. The 1-, 2-, and 3-year cumulative hazard of PC was 1.7%, 2.5%, and 3%, respectively. Median overall and disease-free survival of patients with resected PC were 18 and 12 months (95% CI not computable). Considering HRI who underwent baseline imaging, 6 pancreatic neuroendocrine neoplasms (1 resected) and 1 low-yield surgery (low-grade mixed-intraductal papillary mucinous neoplasm) were also reported. DISCUSSION: PC surveillance in a fully public health care system is feasible and safe, and leads to early PC or premalignant lesions diagnoses, mostly at baseline but also over time.

The Use of a New Dedicated Electrocautery Lumen-Apposing Metal Stent for Gallbladder Drainage in Patients with Acute Cholecystitis.

Aims: Lumen-apposing metal stents (LAMSs) in ultrasonography-guided gallbladder drainage (EUS-GBD) have become increasingly important for high-risk surgical patients. Our study aims to evaluate the technical and clinical success, safety, and feasibility of endoscopic ultrasonography-guided gallbladder drainage using a new dedicated LAMS. Methods: This is a retrospective multicenter study that included all consecutive patients not suitable for surgery who were referred to a tertiary center for EUS-GBD using a new dedicated electrocautery LAMS for acute cholecystitis at eight different centers. Results: Our study included 54 patients with a mean age of 76.48 years (standard deviation: 12.6 years). Out of the 54 endoscopic gallbladder drainages performed, 24 (44.4%) were cholecysto-gastrostomy, and 30 (55.4%) were cholecysto-duodenostomy. The technical success of LAMS placement was 100%, and clinical success was achieved in 23 out of 30 patients (76.67%). Adverse events were observed in two patients (5.6%). Patients were discharged after a median of 5 days post-stenting. Conclusions: EUS-GBD represents a valuable option for high-surgical-risk patients with acute cholecystitis. This new dedicated LAMS has demonstrated a high rate of technical and clinical success, along with a high level of safety.

Endoscopic Submucosal Dissection of Superficial Colorectal Neoplasms at "Challenging Sites" Using a Double-Balloon Endoluminal Interventional Platform: A Single-Center Study.

BACKGROUND: Colonic endoscopic submucosal dissection (ESD) at "challenging sites" such as the cecum, ascending colon, and colonic flexures could be difficult even for expert endoscopists due to poor endoscope stability/maneuverability, steep angles, and thinner wall thickness. A double-balloon endoluminal intervention platform (EIP) has been introduced in the market to fasten and facilitate ESD, particularly when located at difficult sites. Here, we report our initial experience with an EIP comparing the outcomes of an EIP versus standard ESD (S-ESD) at "challenging sites". MATERIALS AND METHODS: We retrospectively collected data on consecutive patients with colonic lesions located in the right colon and at flexures who underwent ESD in our tertiary referral center between March 2019 and May 2023. Endoscopic and clinical outcomes (technical success, en bloc resection rate, R0 resection rate, procedure time, time to reach the lesion, and adverse events) and 6-month follow-up outcomes were analyzed. RESULTS: Overall, 139 consecutive patients with lesions located at these challenging sites were enrolled (EIP: 31 and S-ESD: 108). Demographic characteristics did not differ between groups. En bloc resection was achieved in 92.3% and 93.5% of patients, respectively, in the EIP and S-ESD groups. Both groups showed a comparable R0 resection rate (EIP vs. S-ESD: 92.3% vs. 97.2%). In patients undergoing EIP-assisted ESD, the total procedure time was shorter (96.1 [30.6] vs. 113.6 [42.3] minutes, p = 0.01), and the mean size of the resected lesions was smaller (46.2 ± 12.7 vs. 55.7 ± 17.6 mm, p = 0.003). The time to reach the lesion was significantly shorter in the EIP group (1.9 ± 0.3 vs. 8.2 ± 2.7 min, p ≤ 0.01). Procedure speed was comparable between groups (14.9 vs. 16.6 mm2/min, p = 0.29). Lower adverse events were observed in the EIP patients (3.8 vs. 10.2%, p = 0.31). CONCLUSIONS: EIP allows results that do not differ from S-ESD in the resection of colorectal superficial neoplasms localized in "challenging sites" in terms of efficacy and safety. EIP reduces the time to reach the lesions and may more safely facilitate endoscopic resection.

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.

Metformin rescues migratory deficits of cells derived from patients with periventricular heterotopia.

Periventricular neuronal heterotopia (PH) is one of the most common forms of cortical malformation in the human cortex. We show that human neuronal progenitor cells (hNPCs) derived from PH patients with a DCHS1 or FAT4 mutation as well as isogenic lines had altered migratory dynamics when grafted in the mouse brain. The affected migration was linked to altered autophagy as observed in vivo with an electron microscopic analysis of grafted hNPCs, a Western blot analysis of cortical organoids, and time-lapse imaging of hNPCs in the presence of bafilomycin A1. We further show that deficits in autophagy resulted in the accumulation of paxillin, a focal adhesion protein involved in cell migration. Strikingly, a single-cell RNA-seq analysis of hNPCs revealed similar expression levels of autophagy-related genes. Bolstering AMPK-dependent autophagy by metformin, an FDA-approved drug, promoted migration of PH patients-derived hNPCs. Our data indicate that transcription-independent homeostatic modifications in autophagy contributed to the defective migratory behavior of hNPCs in vivo and suggest that modulating autophagy in hNPCs might rescue neuronal migration deficits in some forms of PH.

Endocuff Vision-Assisted Resection for Difficult Colonic Lesions-Preliminary Results of a Multicenter, Prospective Randomized Pilot Study.

Background-Screening programs for colorectal cancer are implemented due to their ability to reduce mortality. The Endocuff Vision is a new endoscopic device that significantly improves the adenoma detection rate. The primary outcome was to assess the efficacy of ECV in improving stability and reducing operation time during difficult colon polypectomies in a multicenter randomized prospective study. Methods-In a randomized multicenter pilot study, two groups of patients who underwent difficult polypectomies with and without the assistance of Endocuff Vision were compared. Demographics and clinical characteristics of patients were obtained, and polyps' size, morphology, site, and access (SMSA); polypectomy time; and endoscope stability were evaluated. Results-From October 2016 to April 2020, 32 patients were enrolled. In total, 12 patients underwent Endocuff Vision polypectomy, and 20 patients underwent standard polypectomy by using a computer-generated random number table. No statistical differences were found in clinical characteristics, SMSA, and polypectomy time. The most interesting findings were the positive correlations between shaking and SMSA (r = 0.55, p = 0.005) and shaking and polypectomy time (r = 0.745, p < 0.0001). Conclusion-Endocuff Vision seems to be adequately stable during difficult endoscopic resection procedures. The new parameter proposed that shaking is strongly correlated to the stability of the endoscope, the difficulty of the resection (SMSA), and the polypectomy time.

Optimization of laser dosimetry based on patient-specific anatomical models for the ablation of pancreatic ductal adenocarcinoma tumor.

Laser-induced thermotherapy has shown promising potential for the treatment of unresectable primary pancreatic ductal adenocarcinoma tumors. Nevertheless, heterogeneous tumor environment and complex thermal interaction phenomena that are established under hyperthermic conditions can lead to under/over estimation of laser thermotherapy efficacy. Using numerical modeling, this paper presents an optimized laser setting for Nd:YAG laser delivered by a bare optical fiber (300 µm in diameter) at 1064 nm working in continuous mode within a power range of 2-10 W. For the thermal analysis, patient-specific 3D models were used, consisting of tumors in different portions of the pancreas. The optimized laser power and time for ablating the tumor completely and producing thermal toxic effects on the possible residual tumor cells beyond the tumor margins were found to be 5 W for 550 s, 7 W for 550 s, and 8 W for 550 s for the pancreatic tail, body, and head tumors, respectively. Based on the results, during the laser irradiation at the optimized doses, thermal injury was not evident either in the 15 mm lateral distances from the optical fiber or in the nearby healthy organs. The present computational-based predictions are also in line with the previous ex vivo and in vivo studies, hence, they can assist in the estimation of the therapeutic outcome of laser ablation for pancreatic neoplasms prior to clinical trials.

Endoscopic full-thickness resection versus endoscopic submucosal dissection for challenging colorectal lesions: a randomized trial.

BACKGROUND AND AIMS: The optimal endoscopic resection method of challenging colorectal lesions (ie, adenomatous recurrences, nongranular laterally spreading tumors [LST-NGs], lesions without lifting sign <30 mm) is still under debate. The aim of this study was to directly compare endoscopic submucosal dissection (ESD) and endoscopic full-thickness resection (EFTR) for the resection of challenging colorectal lesions in a randomized trial. METHODS: A multicenter, prospective, randomized study was performed in 4 Italian referral centers. Consecutive patients referred for endoscopic resection of challenging lesions were randomly assigned to undergo EFTR or ESD. Primary outcomes were complete (R0) resection and en bloc resection of lesions. Technical success, procedure time, procedure speed, area of the resected specimen, adverse event rate, and local recurrence rate at 6 months were also compared. RESULTS: Overall, 90 patients were included in the study, equally representing the 3 challenging lesion types. Age and sex were comparable in the 2 groups. En bloc resection was obtained in 95.5% of the EFTR group and in 93.3% of the ESD group. R0 resection rate was comparable in the 2 groups (EFTR vs ESD, 42 [93.3%] vs 36 [80%]; P = .06). The EFTR group exhibited a significantly shorter total procedure time (25.6 ± 10.6 minutes vs 76.7 ± 26.4 minutes, P ≤ .01), as well as overall procedure speed (16.8 ± 11.8 mm2/min vs 11.9 ± 9.2 mm2/min, P = .03). The EFTR group had a significantly smaller mean lesion size (21.6 ± 8.3 mm vs 28.7 ± 7.7 mm, P ≤ .01). Adverse events were reported less frequently in patients in the EFTR group (4.44% vs 15.5%, P = .04). CONCLUSIONS: EFTR is comparable to ESD in the treatment of challenging colorectal lesions in terms of safety and efficacy. EFTR is considerably faster than ESD in the treatment of nonlifting lesions and adenoma recurrences. (Clinical trial registration number: NCT05502276.).

Combination of Mucosa-Exposure Device and Computer-Aided Detection for Adenoma Detection During Colonoscopy: A Randomized Trial.

BACKGROUND & AIMS: Both computer-aided detection (CADe)-assisted and Endocuff-assisted colonoscopy have been found to increase adenoma detection. We investigated the performance of the combination of the 2 tools compared with CADe-assisted colonoscopy alone to detect colorectal neoplasias during colonoscopy in a multicenter randomized trial. METHODS: Men and women undergoing colonoscopy for colorectal cancer screening, polyp surveillance, or clincial indications at 6 centers in Italy and Switzerland were enrolled. Patients were assigned (1:1) to colonoscopy with the combinations of CADe (GI-Genius; Medtronic) and a mucosal exposure device (Endocuff Vision [ECV]; Olympus) or to CADe-assisted colonoscopy alone (control group). All detected lesions were removed and sent to histopathology for diagnosis. The primary outcome was adenoma detection rate (percentage of patients with at least 1 histologically proven adenoma or carcinoma). Secondary outcomes were adenomas detected per colonoscopy, advanced adenomas and serrated lesions detection rate, the rate of unnecessary polypectomies (polyp resection without histologically proven adenomas), and withdrawal time. RESULTS: From July 1, 2021 to May 31, 2022, there were 1316 subjects randomized and eligible for analysis; 660 to the ECV group, 656 to the control group). The adenoma detection rate was significantly higher in the ECV group (49.6%) than in the control group (44.0%) (relative risk, 1.12; 95% CI, 1.00-1.26; P = .04). Adenomas detected per colonoscopy were significantly higher in the ECV group (mean ± SD, 0.94 ± 0.54) than in the control group (0.74 ± 0.21) (incidence rate ratio, 1.26; 95% CI, 1.04-1.54; P = .02). The 2 groups did not differ in term of detection of advanced adenomas and serrated lesions. There was no significant difference between groups in mean ± SD withdrawal time (9.01 ± 2.48 seconds for the ECV group vs 8.96 ± 2.24 seconds for controls; P = .69) or proportion of subjects undergoing unnecessary polypectomies (relative risk, 0.89; 95% CI, 0.69-1.14; P = .38). CONCLUSIONS: The combination of CADe and ECV during colonoscopy increases adenoma detection rate and adenomas detected per colonoscopy without increasing withdrawal time compared with CADe alone. CLINICALTRIALS: gov, Number: NCT04676308.

EUS-guided gastroenterostomy using a novel electrocautery lumen apposing metal stent for treatment of gastric outlet obstruction (with video).

BACKGROUND AND AIM: Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) for the treatment of gastric outlet obstruction (GOO) has been actually performed only with one type of electrocautery lumen-apposing metal stents (EC-LAMS). We aimed to evaluate the safety, technical and clinical effectiveness of EUS-GE using a newly available EC-LAMS in patients with malignant and benign GOO. MATERIALS AND METHODS: Consecutive patients who underwent EUS-GE for GOO using the new EC-LAMS at five endoscopic referral centers were retrospectively evaluated. Clinical efficacy was determined utilizing the Gastric Outlet Obstruction Scoring System (GOOSS). RESULTS: Twenty-five patients (64% male, mean age 68.7 ± 9.3 years) met the inclusion criteria; 21 (84%) had malignant etiology. Technically, EUS-GE was successful in all patients, with a mean procedural time of 35 ± 5 min. Clinical success was 68% at 7 days and 100% at 30 days. The mean time to resume oral diet was 11.4 ± 5.8 h, with an improvement of at least one point of GOOSS score observed in all patients. The median hospital stay was 4 days. No procedure-related adverse events occurred. After a mean follow-up of 7.6 months (95% CI 4.6-9.2), no stent dysfunctions were observed. CONCLUSION: This study suggests EUS-GE can be performed safely and successfully using the new EC-LAMS. Future large multicenter prospective studies are needed to confirm our preliminary data.

Fluorescence confocal microscopy for rapid evaluation of EUS fine-needle biopsy in pancreatic solid lesions.

Video 1EUS fine-needle biopsy of a pancreatic solid lesion evaluated with fluorescence confocal microscopy.

Achalasia, from diagnosis to treatment.

INTRODUCTION: Achalasia is an uncommon esophageal motility disorder and is characterized by alterations of the motility of the esophageal body in conjunction with altered lower esophageal sphincter (LES) relaxation. The clinical presentation of patients with achalasia may be complex; however, the most frequent symptom is dysphagia. The management of patients with achalasia is often challenging, due to the heterogeneous clinical presentation. AREAS COVERED: The diagnosis and management of achalasia has significantly improved in the last years due to the growing availability of high-resolution manometry (HRM) and the implementation in the therapeutic armamentarium of new therapeutic endoscopic procedures. Traditional therapeutic strategies include botulinum toxin injected to the LES and pneumatic balloon dilation. On the other hand, surgical treatments contemplate laparoscopic Heller myotomy and, less frequently, esophagectomy. Furthermore, in the last few years, per oral endoscopic myotomy (POEM) has been proposed as the main endoscopic therapeutic alternative to the laparoscopic Heller myotomy. EXPERT OPINION: Diagnosis and treatment of achalasia still represent a challenging area. However, we believe that an accurate up-front evaluation is, nowadays, necessary in addressing patients with achalasia for a more accurate diagnosis as well as for the best treatment options.

Artificial intelligence-assisted optical diagnosis for the resect-and-discard strategy in clinical practice: the Artificial intelligence BLI Characterization (ABC) study.

BACKGROUND: Optical diagnosis of colonic polyps is poorly reproducible outside of high volume referral centers. The present study aimed to assess whether real-time artificial intelligence (AI)-assisted optical diagnosis is accurate enough to implement the leave-in-situ strategy for diminutive (≤ 5 mm) rectosigmoid polyps (DRSPs). METHODS: Consecutive colonoscopy outpatients with ≥ 1 DRSP were included. DRSPs were categorized as adenomas or nonadenomas by the endoscopists, who had differing expertise in optical diagnosis, with the assistance of a real-time AI system (CAD-EYE). The primary end point was ≥ 90 % negative predictive value (NPV) for adenomatous histology in high confidence AI-assisted optical diagnosis of DRSPs (Preservation and Incorporation of Valuable endoscopic Innovations [PIVI-1] threshold), with histopathology as the reference standard. The agreement between optical- and histology-based post-polypectomy surveillance intervals (≥ 90 %; PIVI-2 threshold) was also calculated according to European Society of Gastrointestinal Endoscopy (ESGE) and United States Multi-Society Task Force (USMSTF) guidelines. RESULTS: Overall 596 DRSPs were retrieved for histology in 389 patients; an AI-assisted high confidence optical diagnosis was made in 92.3 %. The NPV of AI-assisted optical diagnosis for DRSPs (PIVI-1) was 91.0 % (95 %CI 87.1 %-93.9 %). The PIVI-2 threshold was met with 97.4 % (95 %CI 95.7 %-98.9 %) and 92.6 % (95 %CI 90.0 %-95.2 %) of patients according to ESGE and USMSTF, respectively. AI-assisted optical diagnosis accuracy was significantly lower for nonexperts (82.3 %, 95 %CI 76.4 %-87.3 %) than for experts (91.9 %, 95 %CI 88.5 %-94.5 %); however, nonexperts quickly approached the performance levels of experts over time. CONCLUSION: AI-assisted optical diagnosis matches the required PIVI thresholds. This does not however offset the need for endoscopists' high level confidence and expertise. The AI system seems to be useful, especially for nonexperts.

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.

New digital confocal laser microscopy may boost real-time evaluation of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) from solid pancreatic lesions: Data from an international multicenter study.

BACKGROUND: Pancreatic cancer is an aggressive malignancy and a leading cause of cancer death worldwide; its lethality is partly linked to the difficulty of early diagnosis. Modern devices for endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) were recently developed to improve targeting and sampling of small lesions, but innovative technologies for microscopic assessment are still lacking. Ex vivo fluorescence confocal laser microscopy (FCM) is a new digital tool for real-time microscopic assessment of fresh unfixed biological specimens, avoiding conventional histological slide preparation and potentially being highly appealing for EUS-FNB specimens. METHODS: This study evaluated the possible role of FCM for immediate evaluation of pancreatic specimens from EUS-FNB. It involved comparison of the interobserver agreement between the new method and standard histological analysis during international multicenter sharing of digital images. Digital images from 25 cases of EUS-FNB obtained with real-time FCM technology and 25 paired digital whole-slide images from permanent conventional paraffin sections were observed by 10 pathologists from different Institutions in Europe, Japan, and the United States, in a blinded manner. The study evaluated 500 observations regarding adequacy, morphological clues, diagnostic categories, and final diagnosis. FINDINGS: Statistical analysis showed substantial equivalence in the interobserver agreement among pathologists using the two techniques. There was also good inter-test agreement in determining sample adequacy and when assigning a diagnostic category. Among morphological features, nuclear enlargement was the most reproducible clue, with very good inter-test agreement. INTERPRETATION: Findings in this study are from international multicenter digital sharing and are published here for the first time. Considering the advantages of FCM digital diagnostics in terms of reduced time and unaltered sample maintenance, the ex vivo confocal laser microscopy may effectively improve traditional EUS-FNB diagnostics, with significant implications for planning modern diagnostic workflow for pancreatic tumors. FUNDING: This study was not supported by any funding source.