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Simple Summary: The aim of our retrospective study was to compare EUS-guided gastroenteroanastomosis (EUS-GE) and enteral stenting (ES) for the palliation of gastric outlet obstruction (GOO) in patients already treated with EUS-guided choledocoduodenostomy (EUS-CDS) for distal malignant biliary obstruction (DMBO). Our results on 77 patients demonstrated that both EUS-GE and ES are safe and effective for palliation of GOO, but EUS-GE is associated with less recurrence of symptoms. Background: EUS-guided gastroenterostomy (EUS-GE) is a novel and effective procedure for the management of malignant gastric outlet obstruction (GOO) with more durable results when compared to enteral stenting (ES). However, data comparing EUS-GE to ES in patients already treated with EUS-guided choledocoduodenostomy (EUS-CDS) for distal malignant biliary obstruction (DMBO) are lacking. We aimed to compare outcomes of EUS-GE and ES for the palliation of GOO in this specific population of patients. Methods: A multicenter, retrospective analysis of patients with DMBO treated by EUS-CDS and subsequent GOO treated by EUS-GE or ES from 2016 to 2021 was conducted. Primary outcomes were overall AEs rate and dysfunction of the EUS-CDS after GOO treatment. Secondary outcomes included clinical success, technical success, procedure duration, length of hospital stay and relapse of GOO symptoms. Results: A total of 77 consecutive patients were included in the study: 25 patients underwent EUS-GE and 52 underwent ES. AEs rate and patency outcomes of the EUS-CDS after GOO treatment were comparable between the two groups (12.5% vs. 17.3%; p = 0.74). No recurrence of GOO symptoms was registered in the EUS-GE group while 11.5% of ES patients had symptoms recurrence, even if not statistically significant (p = 0.16), after a mean follow-up period of 63.5 days. Conclusion: EUS-GE and ES are both effective and safe for the palliation of GOO in patients already treated by EUS-CDS for DMBO with no difference in the biliary stent dysfunction rate and overall AEs. EUS-GE is associated with less recurrence of GOO symptoms. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

To highlight correlations existing between incidence and mortality of pancreatic cancer, and health care indicators in 36 European countries. The Global Burden of Disease (GBD) and Eurostat databases were queried between 2004 and 2019. Incidence and mortality were age-standardized. From Eurostat, indicators regarding expenditure, hospital beds, medical technology, health personnel, physicians by medical specialty and unmet needs for medical examination were extracted. Correlations between GBD and Eurostat data were analysed through mediation analysis applying clustering for countries. Incidence increased by +0.6% per year (p = 0.001) and mortality by +0.3% (p = 0.001), being increasing for most of the European countries considered. Incidence and mortality were strongly positively correlated (p = 0.001). Higher current health expenditure, expenditure in inpatient curative care, the number of available beds, the number of computed tomography scan, magnetic resonance units, practising medical doctors were all related to higher incidence (p < 0.05), whereas the unmet need for medical examinations was related to lower incidence. When the mediator' effect of incidence was handled, these indicators, together with expenditure on outpatient curative cares, the number of pet scanners and of radiation therapy equipment, were related to lower mortality (p < 0.05). Health care environment correlates with reported incidence and mortality of pancreatic cancer. This highlights both that ameliorated socio-economic societies suffer from higher incidence but lower mortality, as well as the epidemiological bias originating from countries' diagnostic ability. [ABSTRACT FROM AUTHOR]

Meta-analyses of randomized controlled trials (RCTs) provide the highest level of evidence but can suffer from type I (false-positive) and II (false-negative) errors, which can be estimated through trial sequential analysis (TSA) demonstrating eventual credibility of results. Aim of the study was to establish through TSA which strategy between neoadjuvant approach or upfront surgery provides best results when treating potentially resectable pancreatic adenocarcinoma. RCTs were searched until September 2021. Intention-to-treat (ITT) overall survival, resection rate, ITT R0 and N0 rates and per-protocol R0 and N0 rates were the outcomes considered. Fixed-effect model was applied. TSA assumed an alpha = 5% and a power = 80%. Four RCTs were identified accruing 325 patients for the ITT analyses and 242 for the per-protocol analyses. Neoadjuvant did not improve survival (p = 0.167) and TSA supported that this result was underpowered, requiring additional 1514 patients to prove credibility. Neoadjuvant reduced resection rate (p = 0.044) but type I error was not avoided. Neoadjuvant credibly increased per-protocol R0 and N0 rates (p = 0.003 and p < 0.001), and TSA showed that these were true-positive findings. Neoadjuvant did not increase ITT R0 rate since randomization (p = 0.169) but TSA showed lack of power. Neoadjuvant credibly increased the ITT N0 rate (p < 0.001) and TSA supported that this was a true positive finding. Neoadjuvant strategy credibly demonstrated superiority over upfront surgery in determine per-protocol R0 resection and N0 rates, as well as ITT N0 rate. For the remaining outcomes, TSA suggested the need of larger samples to exclude type I and II errors. [ABSTRACT FROM AUTHOR]

No study has compared the performance of light microscopy (LM) and whole slide imaging (WSI) for endoscopic ultrasound (EUS) histological acquired tissue samples from pancreatic solid lesions (PSLs). We evaluated the concordance between LM and WSI and the inter- and intra-observer agreements among pathologists on PSLs EUS acquired samples. LM and WSI from 60 patients with PSLs were evaluated by five expert pathologists to define: diagnostic classification, presence of a core, number and percentage of lesional cells. Washout period between evaluations was 3 months. Time of the procedures was also assessed. Forty-eight cell-block and 12 biopsy samples were evaluated. A high concordance between LM and WSI was found. Inter- and intra-observer agreements for diagnostic classification were substantial and complete, respectively. For all the other parameters, the inter-observer agreement was usually higher for LM. For the intra-observer, a substantial agreement was reached regarding the presence of tissue core and the number and the percentage of malignant cells. Median time for performing LM was significantly shorter than for WSI (p < 0.0001). LM and WSI of cell-block and biopsy samples acquired by EUS in PSLs were highly concordant, with a substantial inter-observer and a complete intra-observer agreements regarding diagnostic classification. [ABSTRACT FROM AUTHOR]

BACKGROUND: Pancreatic adenocarcinoma (PDAC) is one of the deadliest human malignancies. Although surgery is currently the only effective treatment for PDAC, most patients survive less than 20 months after tumor resection. OBJECTIVE: The primary goal was to investigate alterations in KRAS, TP53, SMAD4 and CDKN2A/p16 in tumors from patients with exceptionally long survival after surgery. METHODS: Tumors from 15 patients with PDAC that survived more than 55 months after surgery ("LS") were analyzed for KRAS, TP53, IDH1, NRAS and BRAF using next-generation sequencing. SMAD4 and CDKN2A/p16 was tested using immunohistochemistry. MGMT promoter methylation was investigated. RESULTS: Tumors from "LS" have a lower prevalence of KRAS and TP53 mutations and had more frequently SMAD4 retained expression, if compared with that of patients died within 24 months from surgery. The survival of patients with wild-type KRAS and TP53 tumors was more than twice longer than that of patients bearing KRAS and TP53 mutations (90.2 vs. 41.1 months). Patients with KRAS wild-type tumors and that retained SMAD4 expression had a survival twice longer than cases with alterations in both genes (83.8 vs. 36.7 months). Eleven tumors (39.3%) showed MGMT methylation. CONCLUSIONS: Our data indicate that absence of KRAS, TP53 and SMAD4 genetic alterations may identify a subset of pancreatic carcinomas with better outcome. [ABSTRACT FROM AUTHOR]

Objective While the presence of biliary stent significantly decreases the accuracy of endoscopic ultrasound (EUS) for pancreatic head cancer staging, its impact on the EUS-guided sampling accuracy is still debated. Furthermore, data on EUS-fine needle biopsy (EUS-FNB) using core biopsy needles in patients with pancreatic mass and biliary stent are lacking. The aim of this study was to evaluate the influence of biliary stent on the adequacy and accuracy of EUS-FNB in patients with pancreatic head mass. Methods All patients who underwent EUS-guided sampling with core needles of solid pancreatic head masses causing obstructive jaundice were retrospectively identified in a single tertiary referral center. Adequacy, defined as the rate of cases in which a tissue specimen for proper examination was achieved, with and without biliary stent, was the primary outcome measure. The diagnostic accuracy and complication rate were the secondary outcome measures. Results A total of 130 patients with pancreatic head mass causing biliary obstruction were included in the study: 74 cases of them were sampled without stent and 56 cases with plastic stent in situ . The adequacy was 96.4% in the stent group and 90.5% in the group without stent (p = 0.190). No significant differences were observed for sensitivity (88.9% vs. 85.9%), specificity (100% for both groups), and accuracy (89.3% vs . 86.5%) between those with and without stent, respectively. The accuracy was not influenced by the timing of stenting (<48 h or ≥48 h before EUS). No EUS-FNB related complications were recorded. Conclusion The presence of biliary stent does not influence the tissue sampling adequacy, the diagnostic accuracy and the complication rate of EUS-FNB of pancreatic head masses performed with core biopsy needles. [ABSTRACT FROM AUTHOR]

Background: Early detection of small pancreatic cancer is important because expected survival is markedly better for tumors ≤2 cm. A new endoscopic ultrasound-(EUS) guided biopsy needle with side fenestration has been recently developed to enable fine-needle biopsy (FNB) under EUS guidance. The aim of this study was to evaluate the outcome of EUS-FNB using a 22-gauge ProCore needle in solid pancreatic lesions ≤2 cm, in terms of diagnostic accuracy and yield. Methods: From January 2011 to December 2012, all consecutive EUS-guided tissue sampling of small pancreatic lesions (≤2 cm) were performed using 22-gauge ProCore needles; the data of these patients were analyzed retrospectively. Results: Sixty-eight patients with a mean age of 65.7 years were included. The mean lesion size was 16.5 mm (range 5-20). None of the patients developed complications. On pathological examination, the tissue retrieved was judged adequate in 58 out of 68 cases (85.3 %) and the presence of a tissue core was recorded in 36 out of 68 cases (52.9 %). The overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 80, 100, 100, 40, and 82 %, respectively. Conclusion: Our results suggested that EUS-FNB of small pancreatic lesions using a 22-gauge ProCore needle is effective and safe, and supports our hypothesis that EUS-FNB is highly useful in establishing the nature of small pancreatic lesions. [ABSTRACT FROM AUTHOR]

The use of endoscopic ultrasonography has allowed for improved detection and pathologic analysis of fine needle aspirate material for pancreatic lesion diagnosis. The molecular analysis of KRAS has further improved the clinical sensitivity of preoperative analysis. For this reason, the use of highly analytical sensitive and specific molecular tests in the analysis of material from fine needle aspirate specimens has become of great importance. In the present study, 60 specimens from endoscopic ultrasonography fine needle aspirate were analyzed for KRAS exon 2 and exon 3 mutations, using three different techniques: Sanger sequencing, allele specific locked nucleic acid PCR and Next Generation sequencing (454 GS-Junior, Roche). Moreover, KRAS was also tested in wild-type samples, starting from DNA obtained from cytological smears after pathological evaluation. Sanger sequencing showed a clinical sensitivity for the detection of the KRAS mutation of 42.1%, allele specific locked nucleic acid of 52.8% and Next Generation of 73.7%. In two wild-type cases the re-sequencing starting from selected material allowed to detect a KRAS mutation, increasing the clinical sensitivity of next generation sequencing to 78.95%. The present study demonstrated that the performance of molecular analysis could be improved by using highly analytical sensitive techniques. The Next Generation Sequencing allowed to increase the clinical sensitivity of the test without decreasing the specificity of the analysis. Moreover we observed that it could be useful to repeat the analysis starting from selectable material, such as cytological smears to avoid false negative results. [ABSTRACT FROM AUTHOR]

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 (n58) 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 8PC 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 lowyield 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. [ABSTRACT FROM AUTHOR]