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PurposeThe current primary hyperparathyroidism (PHPT) presents as a mild disease. We explored skeletal phenotypes in postmenopausal women affected by PHPT, focusing on fracture prevalence.MethodsPHPT women were retrospectively evaluated at four Italian centers for osteoporosis management (two centers in Milan, n = 244; Cuneo, n = 128; Pisa, n = 131). Data collected from clinical records were analyzed by hierarchical clusterization.ResultsConsidering the whole PHPT series [n = 503, aged 67.0 (61.0–74.0) years], 90% had low bone mineral density (BMD) and approximately 30% reported at least one fracture. Vertebral fractures were associated with older age and lower hypophosphatemia, while women with appendicular fractures were younger with less severe hypophosphatemia. Fractures were predicted by lumbar T-score. By using a clustering approach, we identified four different skeletal phenotypes (cluster, C): C1 (n = 53) and C2 (n = 172) included women with lumbar and femur neck osteopenia, with low prevalence of fractures (11.3%). Osteoporotic PHPT women were grouped into C3 (n = 142) and C4 (n = 136); all women in C4 experienced fractures, were older, and were more frequently affected with cardiovascular diseases. In contrast, women included in C3 never experienced fractures and had a lower body mass index (BMI), though they were characterized by severe reduction in BMD at both lumbar and femur sites. Ionized and total calcium, phosphate, 25hydroxyvitamin D levels, kidney function, and stone prevalence (range, 26.4%–29.0%) were similar among clusters C1, C2, and C4, while unfractured women in C3 showed slightly higher ionized hypercalcemia, lower hypophosphatemia, and higher hypercalciuria with a trend to more frequently develop kidney stones (38.7%) than women in the remaining clusters.ConclusionsSkeletal involvement in women with PHPT presented heterogeneous phenotypes with different prevalence of fractures. Fractures were not related to PHPT severity, suggesting that other factors besides PHPT, such as age, BMI, and lumbar and femur BMD, should be considered in the evaluation of bone involvement in postmenopausal women with PHPT.

Abstract Genome-wide association studies (GWAS) are a powerful tool for detecting variants associated with complex traits and can help risk stratification and prevention strategies against pancreatic ductal adenocarcinoma (PDAC). However, the strict significance threshold commonly used makes it likely that many true risk loci are missed. Functional annotation of GWAS polymorphisms is a proven strategy to identify additional risk loci. We aimed to investigate single-nucleotide polymorphisms (SNP) in regulatory regions [transcription factor binding sites (TFBSs) and enhancers] that could change the expression profile of multiple genes they act upon and thereby modify PDAC risk. We analyzed a total of 12,636 PDAC cases and 43,443 controls from PanScan/PanC4 and the East Asian GWAS (discovery populations), and the PANDoRA consortium (replication population). We identified four associations that reached study-wide statistical significance in the overall meta-analysis: rs2472632(A) (enhancer variant, OR 1.10, 95%CI 1.06,1.13, p = 5.5 × 10−8), rs17358295(G) (enhancer variant, OR 1.16, 95%CI 1.10,1.22, p = 6.1 × 10−7), rs2232079(T) (TFBS variant, OR 0.88, 95%CI 0.83,0.93, p = 6.4 × 10−6) and rs10025845(A) (TFBS variant, OR 1.88, 95%CI 1.50,1.12, p = 1.32 × 10−5). The SNP with the most significant association, rs2472632, is located in an enhancer predicted to target the coiled-coil domain containing 34 oncogene. Our results provide new insights into genetic risk factors for PDAC by a focused analysis of polymorphisms in regulatory regions and demonstrating the usefulness of functional prioritization to identify loci associated with PDAC risk.

Background and objectives: Subepithelial lesions (SELs) of the gastrointestinal (GI) tract present a diagnostic challenge due to their heterogeneous nature and varied clinical manifestations. Usually, SELs are small and asymptomatic; generally discovered during routine endoscopy or radiological examinations. Currently, endoscopic ultrasound (EUS) is the best tool to characterize gastric SELs. Materials and methods: For this review, the research and the study selection were conducted using the PubMed database. Articles in English language were reviewed from August 2019 to July 2024. Results: This review aims to summarize the international literature to examine and illustrate the progress in the last five years of endosonographic diagnostics and treatment of gastric SELs. Conclusions: Endoscopic ultrasound is the preferred option for the diagnosis of sub-epithelial lesions. In most of the cases, EUS-guided tissue sampling is mandatory; however, ancillary techniques (elastography, CEH-EUS, AI) may help in both diagnosis and prognostic assessment.

The expression of several key molecules is altered in parathyroid tumors due to gene mutations, the loss of heterozygosity, and aberrant gene promoter methylation. A set of genes involved in parathyroid tumorigenesis has been investigated in sporadic parathyroid adenomas (PAds). Thirty-two fresh PAd tissue samples surgically removed from patients with primary hyperparathyroidism (PHPT) were collected and profiled for gene, microRNA, and lncRNA expression (n = 27). Based on a gene set including MEN1, CDC73, GCM2, CASR, VDR, CCND1, and CDKN1B, the transcriptomic profiles were analyzed using a cluster analysis. The expression levels of CDC73 and CDKN1B were the main drivers for clusterization. The samples were separated into two main clusters, C1 and C2, with the latter including two subgroups of five PAds (C2A) and nineteen PAds (C2B), both differing from C1 in terms of their lower expression of CDC73 and CDKN1B. The C2A PAd profile was also associated with the loss of TP73, an increased expression of HAR1B, HOXA-AS2, and HOXA-AS3 lncRNAs, and a trend towards more severe PHPT compared to C1 and C2B PAds. C2B PAds were characterized by a general downregulated gene expression. Moreover, CCND1 levels were also reduced as well as the expression of the lncRNAs NEAT1 and VLDLR-AS1. Of note, the deregulated lncRNAs are predicted to interact with the histones H3K4 and H3K27. Patients harboring C2B PAds had lower ionized and total serum calcium levels, lower PTH levels, and smaller tumor sizes than patients harboring C2A PAds. In conclusion, PAds display heterogeneous transcriptomic profiles which may contribute to the modulation of clinical and biochemical features. The general downregulated gene expression, characterizing a subgroup of PAds, suggests the tumor cells behave as quiescent resting cells, while the severity of PHPT may be associated with the loss of p73 and the lncRNA-mediated deregulation of histones.

Background and aim: Guidelines suggest endoscopic resection for rectal neuroendocrine tumors (rNETs) < 10 mm, but the most appropriate resection technique is unclear. In real-life clinical practice, the endoscopic removal of unrecognized rNETs can take place with “simple” techniques and without preliminary staging. The aim of the current study is to report our own experience at a referral center for both neuroendocrine neoplasms and endoscopy. Methods: Retrospective analyses of polypectomies were performed at the Humanitas Research Hospital for rNETs (already diagnosed or previously unrecognized). Results: A total of 19 patients were included, with a median lesion size of 5 mm (range 3–10 mm). Only five lesions were suspected as NETs before removal and underwent endoscopic ultrasound (EUS) before resection, being removed with advanced endoscopic techniques. Unsuspected rNETs were removed by cold polypectomy in eleven cases, EMR in two, and biopsy forceps in one. When described, the margins were negative in four cases, positive in four (R1), and indeterminate in one. The median follow-up was 40 months. A 10 mm polypoid lesion removed with cold snare polypectomy (G2 R1) needed subsequent surgery. Eighteen patients underwent EUS after a median time of 6.5 months from resection. The EUS identified local recurrence after 14 months in a 7 mm polypoid lesion removed with cold snare polypectomy (G1 R1); the lesion was treated with cap-assisted EMR. For all the other lesions, the follow-up was negative. Conclusions: When rNETs are improperly removed without prior staging, caution must be exercised. The data from our cohort suggest that even if inappropriate resection had happened, patients may be safely managed with early EUS evaluation.

Abstract Background The genomes of present-day non-Africans are composed of 1–3% of Neandertal-derived DNA as a consequence of admixture events between Neandertals and anatomically modern humans about 50–60 thousand years ago. Neandertal-introgressed single nucleotide polymorphisms (aSNPs) have been associated with modern human disease-related traits, which are risk factors for pancreatic ductal adenocarcinoma (PDAC), such as obesity, type 2 diabetes, and inflammation. In this study, we aimed at investigating the role of aSNPs in PDAC in three Eurasian populations. Results The high-coverage Vindija Neandertal genome was used to select aSNPs in non-African populations from 1000 Genomes project phase 3 data. Then, the association between aSNPs and PDAC risk was tested independently in Europeans and East Asians, using existing GWAS data on more than 200 000 individuals. We did not find any significant associations between aSNPs and PDAC in samples of European descent, whereas, in East Asians, we observed that the Chr10p12.1-rs117585753-T allele (MAF = 10%) increased the risk to develop PDAC (OR = 1.35, 95%CI 1.19–1.54, P = 3.59 × 10–6), with a P-value close to a threshold that takes into account multiple testing. Conclusions Our results show only a minimal contribution of Neandertal SNPs to PDAC risk.

Aim: The gold standard of care for pancreatic adenocarcinoma is the integrated treatment of surgery and chemotherapy (ChT), but about 50% of patients present with unresectable disease. Our study evaluated the efficacy in terms of local control, survival and safety of stereotactic body radiation therapy (SBRT) in locally advanced pancreatic cancer (LAPC). Methods: A retrospective study (STEP study) analyzed patients with LAPC treated with a dose of 45 Gy in 6 fractions. Local control (LC), distant progression free survival (DPFS), overall survival (OS) and toxicity were analyzed according to the Kaplan-Meier method. Results: A total of 142 patients were evaluated. Seventy-six patients (53.5%) received induction ChT before SBRT. The median follow-up was 11 months. One-, 2- and 3-year LC rate was 81.9%, 69.1% and 58.5%. Median DPFS was 6.03 months; 1- and 2-year DPFS rate was 19.9% and 4.5%. Median OS was 11.6 months and 1-, 2- and 3-year OS rates were 45.4%, 16.1%, and 9.8%. At univariate analysis, performed by the log-rank test, age < 70 years (p = 0.037), pre-SBRT ChT (p = 0.004) and post-SBRT ChT (p = 0.019) were associated with better OS. No patients experienced G3 toxicity. Conclusion: SBRT represents an effective and safe therapeutic option in the multimodal treatment of patients with LAPC in terms of increased LC. When SBRT was sequentially integrated with ChT, the treatment proved to be promising in terms of OS as well.

There are different cancers in the peri-ampullary region, including pancreatic ductal adenocarcinoma (PDAC), duodenum cancers (DCs), and ampullary adenocarcinoma (AAC). Here, significant morphological–molecular characterizations should be necessary for the distinction of primary tumours and classifications of their subtypes of cancers. The sub classification of AACs might include up to five different variants, according to different points of view, concerning the prevalence of the two more-cellular components found in the ampulla. In particular, regarding the AACs, the most important subtypes are represented by the intestinal (INT) and the pancreato-biliary (PB) ones. The subtyping of AACs is essential for diagnosis, and their identifications have been impacting clinical management responses to treatments and overall survival (os) after surgery. Pb is associated with a worse clinical outcome. Otherwise, the criteria, through which are possible to attribute its subtype classification, are not well established. A triage of immune markers represented by CK7, CK20, and CDX-2 seem to represent the best compromise in order to split the cohort of AAC patients in the INT and PB groups. The test of choice for the sub-classification of AACs is represented by the immuno-histochemical approach, in which its molecular classification acquires its diagnostic, predictive, and prognostic value for both the INT and PB patients.

Gastrojejunostomy is the principal method of palliation for unresectable malignant gastric outlet obstructions (GOO). Gastrojejunostomy was traditionally performed as a surgical procedure with an open approach butrecently, notable progress in the development of minimally invasive procedures such as laparoscopic gastrojejunostomies have emerged. Additionally, advancements in endoscopic techniques, including endoscopic stenting (ES) and endoscopic ultrasound-guided gastroenterostomy (EUS-GE), are becoming more prominent. ES involves the placement of self-expandable metal stents (SEMS) to restore luminal patency. ES is commonly the first choice for patients deemed unfit for surgery or at high surgical risk. However, although ES leads to rapid improvement of symptoms, it carries limitations like higher stent dysfunction rates and the need for frequent re-interventions. Recently, EUS-GE has emerged as a potential alternative, combining the minimally invasive nature of the endoscopic approach with the long-lasting effects of a gastrojejunostomy. Having reviewed the advantages and disadvantages of these different techniques, this article aims to provide a comprehensive review regarding the management of unresectable malignant GOO.

Background: The endoscopic submucosal dissection (ESD) is a technically demanding and time-consuming procedure, with an increased risk of adverse events compared to standard endoscopic resection techniques. The main difficulties are related to the instability of the operating field and to the loss of traction. We aimed to evaluate in a pilot trial a new endoscopic platform [tissue retractor system (TRS); ORISE, Boston scientific Co., Marlborough, MA, USA], designed to stabilize the intraluminal space, and to provide tissue retraction and counter traction. Method: We prospectively enrolled all consecutive patients who underwent an ESD for sigmoid/rectal lesions. The primary outcome was the rate of technical feasibility. Further technical aspects such as en-bloc and R0 resection rate, number of graspers used, circumferential incision time, TRS assemblage time, submucosal dissection time, and submucosal dissection speed were provided. Clinical outcomes (recurrence rate and adverse events) were recorded as well. Results: In all, 10 patients (M/F 4/6, age: 70.4 ± 11.0 years old) were enrolled. Eight out of 10 lesions were located in the rectum. Average lesion size was 31.2 ± 2.7 mm, and mean lesion area was 1628.88 ± 205.3 mm 2 . The two sigmoid lesions were removed through standard ESD, because the platform assemblage failed after several attempts. All rectal lesions were removed in an en-bloc fashion. R0 resection was achieved in 7/8 (87.5%) patients in an average procedure time of 60.5 ± 23.3 min. None of the patients developed neither intraprocedural nor postprocedural adverse events. Conclusion: TRS-assisted ESD is a feasible option when used in the rectum, with promising result in terms of efficacy and safety outcomes. Nevertheless, our pilot study underlines few technical limitations of the present platform that need to be overcome before the system could be widely and routinely used.

This review article provides a comprehensive overview of the evolving techniques in image-enhanced endoscopy (IEE) for the characterization of colorectal polyps, and the potential of artificial intelligence (AI) in revolutionizing the diagnostic accuracy of endoscopy. We discuss the historical use of dye-spray and virtual chromoendoscopy for the characterization of colorectal polyps, which are now being replaced with more advanced technologies. Specifically, we focus on the application of AI to create a “virtual biopsy” for the detection and characterization of colorectal polyps, with potential for replacing histopathological diagnosis. The incorporation of AI has the potential to provide an evolutionary learning system that aids in the diagnosis and management of patients with the best possible outcomes. A detailed analysis of the literature supporting AI-assisted diagnostic techniques for the detection and characterization of colorectal polyps, with a particular emphasis on AI’s characterization mechanism, is provided. The benefits of AI over traditional IEE techniques, including the reduction in human error in diagnosis, and its potential to provide an accurate diagnosis with similar accuracy to the gold standard are presented. However, the need for large-scale testing of AI in clinical practice and the importance of integrating patient data into the diagnostic process are acknowledged. In conclusion, the constant evolution of IEE technology and the potential for AI to revolutionize the field of endoscopy in the future are presented.

Pancreatic surgery is extremely challenging and demands an extended learning curve to be executed with a low incidence of post-operative complications. The soft consistency of the human pancreas poses a primary challenge for pancreatic surgeons. This study aimed to analyze the preliminary mechanical characteristics of the human pancreas to develop a realistic synthetic phantom for surgical simulations in the near future. Pancreatic specimens, comprehensive of the pancreatic parenchyma and main pancreatic duct, were collected during pancreatic resections and analyzed through nano-bio-indentation (BioindenterTM UNHT3 Bio, Anton Paar GmbH, Graz, Austria) to measure the elastic modulus. Comparisons were made between slow and fast loading rates, immediate and post-freezing analyses, and multipoint indentations. The results demonstrated that a slow loading rate (30 μN/min), immediate analysis, and multipoint measurements are crucial for obtaining accurate values of the elastic modulus of the human pancreas (1.40 ± 0.47 kPa). In particular, the study revealed that analysis after freezing could impact the outcomes of the indentation. Moreover, the study suggested that both the pancreatic parenchyma and the main pancreatic duct should be analyzed to achieve a more precise and comprehensive definition of the. mechanical features of the pancreas. These preliminary findings represent the initial steps toward defining the consistency and mechanical characteristics of human pancreatic tissue with the goal of creating a realistic synthetic phantom.

Endoscopic retrograde cholangiopancreatography (ERCP) is considered the preferred method for managing biliary obstructions. However, the prevalence of surgically modified anatomies often poses challenges, making the standard side-viewing duodenoscope unable to reach the papilla in most cases. The increasing instances of surgically altered anatomies (SAAs) result from higher rates of bariatric procedures and surgical interventions for pancreatic malignancies. Conventional ERCP with a side-viewing endoscope remains effective when there is continuity between the stomach and duodenum. Nonetheless, percutaneous transhepatic biliary drainage (PTBD) or surgery has historically been used as an alternative for biliary drainage in malignant or benign conditions. The evolving landscape has seen various endoscopic approaches tailored to anatomical variations. Innovative methodologies such as cap-assisted forward-viewing endoscopy and enteroscopy have enabled the performance of ERCP. Despite their utilization, procedural complexities, prolonged durations, and accessibility challenges have emerged. As a result, there is a growing interest in novel enteroscopy and endoscopic ultrasound (EUS) techniques to ensure the overall success of endoscopic biliary drainage. Notably, EUS has revolutionized this domain, particularly through several techniques detailed in the review. The rendezvous approach has been pivotal in this field. The antegrade approach, involving biliary tree puncturing, allows for the validation and treatment of strictures in an antegrade fashion. The EUS-transmural approach involves connecting a tract of the biliary system with the GI tract lumen. Moreover, the EUS-directed transgastric ERCP (EDGE) procedure, combining EUS and ERCP, presents a promising solution after gastric bypass. These advancements hold promise for expanding the horizons of comprehensive and successful biliary drainage interventions, laying the groundwork for further advancements in endoscopic procedures.

Background and study aims Artificial intelligence (AI) is set to impact several fields within gastroenterology. In gastrointestinal endoscopy, AI-based tools have translated into clinical practice faster than expected. We aimed to evaluate the status of research for AI in gastroenterology while predicting its future applications. Methods All studies registered on Clinicaltrials.gov up to November 2021 were analyzed. The studies included used AI in gastrointestinal endoscopy, inflammatory bowel disease (IBD), hepatology, and pancreatobiliary diseases. Data regarding the study field, methodology, endpoints, and publication status were retrieved, pooled, and analyzed to observe underlying temporal and geographical trends. Results Of the 103 study entries retrieved according to our inclusion/exclusion criteria, 76 (74 %) were based on AI application to gastrointestinal endoscopy, mainly for detection and characterization of colorectal neoplasia (52/103, 50 %). Image analysis was also more frequently reported than data analysis for pancreaticobiliary (six of 10 [60 %]), liver diseases (eight of nine [89 %]), and IBD (six of eight [75 %]). Overall, 48 of 103 study entries (47 %) were interventional and 55 (53 %) observational. In 2018, one of eight studies (12.5 %) were interventional, while in 2021, 21 of 34 (61.8 %) were interventional, with an inverse ratio between observational and interventional studies during the study period. The majority of the studies were planned as single-center (74 of 103 [72 %]) and more were in Asia (45 of 103 [44 %]) and Europe (44 of 103 [43 %]). Conclusions AI implementation in gastroenterology is dominated by computer-aided detection and characterization of colorectal neoplasia. The timeframe for translational research is characterized by a swift conversion of observational into interventional studies.

This narrative review provides an overview of the application of endoscopic ultrasound-guided biliary drainage (EUS-BD), including EUS-guided gallbladder drainage (EUS-GBD), for the treatment of malignant biliary obstruction. EUS-BD has demonstrated excellent technical and clinical success rates, with lower rates of adverse events when compared with percutaneous trans-hepatic biliary drainage (PTBD). EUS-BD is currently the preferred alternative technique for biliary drainage (BD) in patients with distal malignant biliary obstruction (DMBO) after failed endoscopic retrograde cholangiopancreatography (ERCP). Particularly, this review will focus on EUS-BD performed with the use of lumen apposing metal stent (LAMS). The introduction of these innovative devices, followed by the advent of electrocautery-enhanced LAMS (EC-LAMS), gave the procedure a great technical implementation and a widespread application.

Over the last two decades, endoscopic eradication therapy has been established as the therapeutic strategy of choice for patients with Barrett’s oesophagus-related dysplasia and early oesophageal adenocarcinoma. With a multimodal approach, ablative therapies have been highly effective in achieving remarkable eradication rates of metaplastic epithelium with an acceptable adverse event rate. Among ablative techniques, radiofrequency ablation is currently considered as the first-line option as its efficacy and safety are strongly supported by relevant data. Nevertheless, radiofrequency ablation is costly, and not universally available, or applicable to every situation. Moreover, primary failure and recurrence rates are not negligible. In the last few years, cryotherapy techniques and hybrid argon plasma coagulation have been increasingly assessed as potential novel ablative therapies. Preliminary data have been promising and suggest that they may even have a role as first-line options, alternatively to radiofrequency ablation. The aim of this review is to provide a practical guide for the ablation of Barrett’s oesophagus, with emphasis on the different ablative options.

Abstract Background Serous cysto-adenoma (SCA) is a rare benign neoplasm of the pancreas. SCA can mimic other pancreatic lesions, such as neuroendocrine tumours. 68Gallium-DOTA-peptide Positron Emission Tomography (PET) is able to image in vivo the over-expression of the somatostatin receptors, playing an important role for the identification of neuroendocrine neoplasms. Case presentation We reported a case of 63-year-old man, with a solid lesion of 7 cm of diameter of the body–tail of the pancreas. Two fine-needle-aspirations (FNA) were inconclusive. A 68Ga-DOTA-peptide PET-CT revealed a pathological uptake of the pancreatic lesion. The diagnosis of a pancreatic neuroendocrine neoplasm was established and a laparoscopic distal splenopancreatectomy and cholecystectomy was performed. Final histopathological report revealed the presence of a micro-cystic SCA. Conclusions The current case firstly reports a pancreatic SCA showing increased radiopharmaceutical uptake at 68Ga-DOTA-peptide PET-CT images. This unexpected finding should be taken into account during the diagnostic algorithm of a pancreatic lesion, in order to minimize the risk of misdiagnosis and overtreatment of SCA.

Background and study aims The role of endoscopic submucosal dissection (ESD) for colorectal lesions in Western communities is unclear and its adoption is still limited. The aim of this study is to assess the long-term outcomes of a large cohort of patients treated with colorectal ESD in a tertiary Western center. Patients and methods A retrospective analysis was conducted on patients treated by ESD for superficial colorectal lesions between February 2011 and November 2019. The primary outcome was the recurrence rate. Secondary outcomes were en-bloc and R0 resection rates, procedural time, adverse events (AEs), and need for surgery. The curative resection rate was assessed for submucosal invasive lesions. Results A total of 327 consecutive patients, median age 69 years (IQR 60–76); 201 men (61.5 %) were included in the analysis. Of the lesions, 90.8 % were resected in an en-bloc fashion. The rate of R0 resection was 83.1 % (217/261) and 44.0 % (29/66) for standard and hybrid ESD techniques, respectively. Submucosal invasion and piecemeal resection independently predicted R1 resections. A total of 18(5.5 %) intra-procedural AEs (perforation:11, bleeding:7) and 12(3.7 %) post-procedural AEs occurred (perforation:2, bleeding: 10). Eighteen adenoma recurrences per 1,000 person-years (15cases, 5.6 %) were detected after a median follow-up time of 36 months. All recurrences were detected within 12 months. No carcinoma recurrences were observed. R1 resection status and intra-procedural AEs independently predicted recurrences with seven vs 150 recurrences per 1,000 person-years in the R0 vs R1 group, respectively. Conclusions Colorectal ESD is a safe and effective option for managing superficial colorectal neoplasia in a Western setting, with short and long-terms outcomes comparable to Eastern studies. En-bloc R0 resection and absence of intra-procedural AEs are associated with reduced risk of recurrence.

Pancreatic neuroendocrine tumor (PNET) behavior assessment is a daily challenge for physicians. Modern PNET management varies from a watch-and-wait strategy to surgery depending on tumor aggressiveness. Therefore, the aggressiveness definition plays a pivotal role in the PNET work-up. The aggressiveness of PNETs is mainly based on the dimensions and histological grading, with sometimes a lack of specificity and sensibility. In the last twenty years, EUS has become a cornerstone in the diagnostic phase of PNET management for its high diagnostic yield and the possibility of obtaining a histological specimen. The number of EUS applications in the PNET work-up has been rapidly increasing with new and powerful possibilities. The application of contrast has led to an important step in PNET detection; in recent years, it has been gaining interesting applications in aggressiveness assessment. In this review, we underline the latest experiences and opportunities in the behavior assessment of PNETs using contact-enhanced EUS and contested enhanced harmonic EUS with a particular focus on the future application and possibility that these techniques could provide.

Although 21 pancreatic cancer susceptibility loci have been identified in individuals of European ancestry through genome-wide association studies (GWASs), much of the heritability of pancreatic cancer risk remains unidentified. A recessive genetic model could be a powerful tool for identifying additional risk variants. To discover recessively inherited pancreatic cancer risk loci, we performed a re-analysis of the largest pancreatic cancer GWAS, the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4), including 8,769 cases and 7,055 controls of European ancestry. Six single nucleotide polymorphisms (SNPs) showed associations with pancreatic cancer risk according to a recessive model of inheritance. We replicated these variants in 3,212 cases and 3,470 controls collected from the PANcreatic Disease ReseArch (PANDoRA) consortium. The results of the meta-analyses confirmed that rs4626538 (7q32.2), rs7008921 (8p23.2) and rs147904962 (17q21.31) showed specific recessive effects (p10−3), although none of the six SNPs reached the conventional threshold for genome-wide significance (p < 5×10−8). Additional bioinformatic analysis explored the functional annotations of the SNPs and indicated a possible relationship between rs36018702 and expression of the BCL2L11 and BUB1 genes, which are known to be involved in pancreatic biology. Our findings, while not conclusive, indicate the importance of considering non-additive genetic models when performing GWAS analysis. The SNPs associated with pancreatic cancer in this study could be used for further meta-analysis for recessive association of SNPs and pancreatic cancer risk and might be a useful addiction to improve the performance of polygenic risk scores.

Genetic factors play an important role in the susceptibility to pancreatic cancer (PC). However, established loci explain a small proportion of genetic heritability for PC; therefore, more progress is needed to find the missing ones. We aimed at identifying single nucleotide polymorphisms (SNPs) affecting PC risk through effects on micro-RNA (miRNA) function. We searched in silico the genome for SNPs in miRNA seed sequences or 3 prime untranslated regions (3'UTRs) of miRNA target genes. Genome-wide association data of PC cases and controls from the Pancreatic Cancer Cohort (PanScan) Consortium and the Pancreatic Cancer Case–Control (PanC4) Consortium were re-analyzed for discovery, and genotyping data from two additional consortia (PanGenEU and PANDoRA) were used for replication, for a total of 14,062 cases and 11,261 controls. None of the SNPs reached genome-wide significance in the meta-analysis, but for three of them the associations were in the same direction in all the study populations and showed lower value of p in the meta-analyses than in the discovery phase. Specifically, rs7985480 was consistently associated with PC risk (OR = 1.12, 95% CI 1.07–1.17, p = 3.03 × 10−6 in the meta-analysis). This SNP is in linkage disequilibrium (LD) with rs2274048, which modulates binding of various miRNAs to the 3'UTR of UCHL3, a gene involved in PC progression. In conclusion, our results expand the knowledge of the genetic PC risk through miRNA-related SNPs and show the usefulness of functional prioritization to identify genetic polymorphisms associated with PC risk.

Background and study aims The standard method for obtaining samples during endoscopic ultrasonography (EUS) is fine-needle aspiration (FNA), the accuracy of which can be affected by the presence of a cytopathologist in endoscopy room (rapid on-site evaluation [ROSE]). With the introduction of fine-needle biopsy (FNB), macroscopic on-site evaluation (MOSE) of a acquired specimen has been proposed. Only a few studies have evaluated the role of MOSE and in all except one, a 19G needle was used. Our primary aim was to evaluate the diagnostic yield and accuracy of MOSE with different needle sizes and the secondary aim was to identify factors influencing the yield of MOSE. Patients and methods Data from patients who underwent EUS-FNB for solid lesions, with MOSE evaluation of the specimen, were collected in six endoscopic referral centers. Results A total of 378 patients (145 F and 233 M) were enrolled. Needles sizes used during the procedures were 20G (42 %), 22G (45 %), and 25G (13 %). The median number of needle passes was two (IQR 2–3). The overall diagnostic yield of MOSE was of 90 % (confidence interval [CI] 86 %–92 %). On multivariable logistic regression analysis, variables independently associated with the diagnostic yield of MOSE were a larger needle diameter (20G vs. 25G, OR 11.64, 95 %CI 3.5–38.71; 22G vs. 25G, OR 6.20, 95 %CI 2.41–15.90) and three of more needle passes (OR 3.39, 95 %CI 1.38–8.31). Conclusions MOSE showed high diagnostic yield and accuracy. Its yield was further increased if performed with a large size FNB needles and more than two passes.

One of the main challenges encountered by endosonographers is performing diagnostic and interventional pancreato-biliary endoscopic ultrasound (EUS) procedures in the presence of surgically altered upper gastrointestinal anatomy. We describe the water-filled technique (WFT) for EUS examination and treatment of the pancreato-biliary region in patients with surgically altered upper gastrointestinal anatomy. Using the WFT, the scope is advanced up to the gastro-jejunal anastomosis and, after placing the tip of the scope 2 cm beyond it, enlargement of the jejunal lumen is obtained by water instillation of the jejunal loop. An enlargement of more than 1.5 cm allows advancement of the tip of the scope under EUSguidance up to the duodenum, in a retrograde way. The WFT is useful for reaching the ampullary area and performing diagnostic and therapeutic EUS in patients with surgically altered anatomy. The technique is also reproducible and can be easily used by endoscopists who regularly perform EUS.

Background and study aims Pancreatic cancer represents the fourth most common cause of cancer-related deaths in Western countries and the need of a low-risk investigation to obtain an accurate histopathological diagnosis has become increasingly pressing. Endoscopic ultrasonography (EUS) with fine-needle aspiration (FNA) is the standard method for obtaining samples from pancreatic masses. In recent years, there has been an increasing need to obtain histological specimens during EUS procedures, rather than cytological ones, to guide oncological treatment options, leading to the so-call “FNB concept.” Different needles have been developed for fine-needle biopsy (FNB) in recent years, enabling acquisition of larger specimens on which to perform histological and molecular analyses. The aim of this narrative review was to assess the role of EUS-guided FNA and FNB in patients with pancreatic masses, and to identify which needle and which acquisition technique should be used to improve tissue acquisition.

Background and study aims Little is known about outcomes of biliopancreatic endosonography (EUS) in patients with surgically altered upper gastrointestinal (gastrointestinal) anatomy. We aimed to assess the rate of procedural success and EUS-related adverse events (AEs), according to post-surgical anatomies. Patients and methods Retrospective study including patients with post-surgical altered upper gastrointestinal anatomy who underwent EUS for evaluation of the biliopancreatic region between January 2008 and June 2018 at eight European centers. Results Of 242 patients (162 males, mean age 66.4 ± 12.5), 86 had (35.5 %) Billroth II, 77 (31.8 %) pancreaticoduodenectomy, 23 (9.5 %) Billroth I, 19 (7.9 %) distal esophagectomy, 15 (6.2 %) total gastrectomy, 14 (5.8 %) sleeve gastrectomy, and eight (3.3 %) Roux-en-Y. Sleeve gastrectomy, Billroth I, and pancreaticoduodenectomy were associated with high rates of success (100 %, 95.7 %, and 92.2 %, respectively). Visualization of the head of the pancreas was significantly impacted by total gastrectomy, Billroth II, and Roux-en-Y (success rates 6.7 %, 53.7 %, and 57.1 %, respectively). Examination of the pancreatic body and tail was impaired in esophagectomy and total gastrectomy (82.4 % and 71.4 %, respectively). Technical success and diagnostic accuracy of EUS-guided tissue acquisition (EUS-TA) was 78.2 % and 71.3 % (95 % CI, 60.6–80.5), respectively. Four (1.6 %) AEs were observed: one mucosal tearing in a Billroth II patient, one cardiac arrest in a distal esophagectomy patient, one bleed after EUS-TA in a Billroth I patient, and one acute pancreatitis after EUS-TA in a sleeve gastrectomy patient. Conclusions The yield of bilio-pancreatic EUS is dependent on lesion location and surgery type. Before considering EUS in these patients, one must carefully consider whether the lesion may be approachable by EUS.

Background and study aims EUS-FNA has suboptimal accuracy in diagnosing gastrointestinal subepithelial tumors (SETs). EUS-guided 22-gauge fine needle biopsy (EUS-FNB) and single-incision with needle knife (SINK) were proposed to increase accuracy of diagnosis. This study aimed to prospectively compare the diagnostic accuracy and safety of EUS-FNB with SINK in patients with upper gastrointestinal SETs. Patients and methods All adult patients referred for EUS evaluation of upper gastrointestinal SETs ≥ 15 mm in size were eligible for inclusion. Patients were randomized to undergo EUS-FNB or SINK. Lesions were sampled with a 22-gauge reverse beveled core needle in the EUS-FNB group and by a conventional needle-knife sphincterotome and biopsy forceps in the SINK group. Patients were blinded to the technique used. The primary outcome was diagnostic accuracy. Secondary outcomes included adverse events, histological yield and procedure duration. Study enrollment was terminated early due to poor recruitment. Results A total of 56 patients (31 male (55.37 %); mean age, 67.41 ± 12.70 years) were randomized to either EUS-FNB (n = 26) or SINK (n = 30). Technical success was 96.15 % and 96.66 %, respectively. The majority of lesions were gastrointestinal stromal tumors (51.78 %). No significant difference was found between EUS-FNB and SINK in terms of diagnostic accuracy for a malignant or benign disease (76 % vs. 89.28 %, respectively; P = 0.278). The rate of adverse events (none severe) was also comparable (7.69 % vs. 10 %, respectively; P = 1.0) including two abdominal pain episodes in the EUS-FNB group compared to two delayed bleeding (one requiring hospitalization and radiologic embolization) and 1 abdominal pain in the SINK group. Conclusion EUS-FNB and SINK are equally effective techniques for upper gastrointestinal SETs sampling. SINK can be associated with mild to moderate delayed bleeding.

Background Recently, a novel lumen-apposing fully covered self-expanding metal stent (LA-FCSEMS) mounted on an electrocautery-enhanced delivery system has been developed to perform endoscopic ultrasound (EUS)-guided transluminal drainage. From early experience, however, release of the proximal flange of the stent has mostly been done using endoscopic view guidance to ensure proper positioning. Aim We describe a new technique that we have named the Intra-Channel Stent Release Technique (ICSRT) to perform stent placement under complete EUS control, without the use of either fluoroscopic or endoscopic views. Material and methods Data on all consecutive patients who underwent EUS-guided drainage using the new ICSRT between June 2014 and April 2016 were retrospectively retrieved from two institution databases. All EUS procedures were performed by experienced endoscopists with the patient under conscious or deep sedation. The total procedure and stent deployment time, and adverse events related to stent positioning with the ICSRT were evaluated. Results One hundred consecutive patients (51 women; mean age ± SD, 66 ± 15.2 years, range 34 – 95) underwent EUS-guided transluminal drainage with the Hot AXIOS™ device using the new ICSRT. The procedure was technically successful in all but one patient (1 %). The mean total procedural time was 21.9 minutes (range 7 – 50), while the mean time for stent placement was 3.2 minutes (range 1 – 15). No major adverse events occurred. Discussion The ICSRT has been used to deploy the newly developed lumen-apposing FCSEMS under complete EUS guidance without fluoroscopic and/or endoscopic assistance. The technique appears to be safe and highly effective and should be learned by all interventional endosonographers in order to be able to perform drainage in all clinical scenarios.

Optimal management of pediatric endoscopy requires a multidisciplinary approach. In most hospitals, endoscopy in pediatric patients is performed by conventional gastroenterologists and only a few centers have specialized pediatric gastroenterologists. This is due to the fact that the number of pediatric gastroenterologists is limited and not all of them are experienced in endoscopic techniques. However, there are also some pediatric centers offering a high-quality and high-volume endoscopy service provided by very experienced pediatric gastroenterologists. Up to now, the literature on pediatric endoscopy is rather sparse. In this article, we describe current knowledge and practice of endoscopic procedures in pediatric patients, which should be relevant for both the adult and pediatric gastroenterologists.

Introduction: Endoscopic ultrasonography (EUS) is a validated technique allowing precise diagnosis and staging of pancreatic, biliary and ampullary disease. Developments in instruments and accessories have led to a more extensive use of this technology to perform operations. The use of EUS as an operative technique, alone or in conjunction with other endoscopic procedures, has already been described in the literature in several reports. However, despite the use of EUS, fluoroscopy has always been required to perform these operations. There are no data in the literature describing the feasibility, safety and efficacy of operative EUS in the treatment of common bile duct (CBD) obstruction, following a malignant or benign disease, performed completely under EUS guidance without fluoroscopic assistance. Methods: In this series we describe three cases of EUS treatment of CBD diseases performed without fluoroscopic assistance. Results: All the cases were treated by EUS without fluoroscopic assistance and no complications were encountered. Conclusion: Operative EUS without fluoroscopy appears to be a feasible technique. Its major advantages could be to shorten the examination time and to enable biliary or pancreatic operative endoscopy in patients in whom fluoroscopy could be dangerous, such as pregnant women. The endoscopist should have a good training both in EUS and endoscopic retrograde cholangiopancreatography. Prospective, larger studies are needed to confirm our preliminary data.

Background and Study Aims The use of fluoroscopy in gastrointestinal endoscopy is an essential aid in advanced endoscopic interventions. However, it also raises concerns about radiation exposure. This study aimed to develop consensus-based statements for the safe and effective use of fluoroscopy in gastrointestinal endoscopy, prioritizing the safety and well-being of healthcare workers and patients. Methods A modified Delphi approach was employed to achieve consensus over three rounds of surveys. Proposed statements were generated in round 1. In the second round, panelists rated potential statements on a 5-point scale, with consensus defined as ≥80% agreement. Statements were subsequently prioritized in round 3, using a 1 (lowest priority) to 10 (highest priority) scale. Results Forty-six experts participated, consisting of 34 therapeutic endoscopists and 12 endoscopy nurses from six continents, with an overall 45.6% female representation (n=21). Forty-three item statements were generated in the first round. Out of these, 31 statements achieved consensus after the second round. These statements were categorized into General Considerations (n=6), Education (n=10), Pregnancy (n=4), Family Planning (n=2), Patient Safety (n=4), and Staff Safety (n=5). In the third round, accepted statements received mean priority scores ranging from 7.28 to 9.36, with 87.2% of statements rated as very high priority (mean score of ≥9). Conclusion This study presents consensus-based statements for the safe and effective use of fluoroscopy in gastrointestinal endoscopy, addressing the well-being of healthcare workers and patients. These consensus-based statements aim to mitigate the risks associated with radiation exposure while maintaining the benefits of fluoroscopy, ultimately promoting a culture of safety in healthcare settings.