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BACKGROUND/OBJECTIVES Within the last two decades, an increased incidence of acute pancreatitis (AP) has been reported in childhood, with some progressing to acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP). Training future pancreatologists is critical to improve the care of children with pancreatic diseases. There are no studies to assess whether the pediatric gastroenterology (GI) fellowship curriculum prepares specialists to care for children with pancreatic diseases. METHODS An electronic survey was distributed to all North American Pediatric Gastroenterology Fellows. The survey included 31 questions on pancreatology training including academic resources, research experience, clinical exposure, clinical confidence, and career plans. RESULTS A total of 112 (25.8%) fellows responded from 41 (41/72, 56.9%) training centers in North America. Pancreas-specific didactic lectures were reported by 90.2% (n = 101); 49.5% (50/101) had at least quarterly or monthly lectures. Clinical confidence (Likert 4-5) was highest in managing and treating AP (94.6% and 93.8% respectively), relatively lower for ARP (84.8% and 71.4%) and lowest for CP (63.4% and 42.0%). Confidence in diagnosing both ARP and CP was associated with the variety of pancreatic diseases seen (p

Background and study aims Endoscopic retrograde cholangiopancreatography (ERCP) plays a major role in biliary strictures, with brushing being a cheap and fast method to acquire a cytological specimen, despite a sensitivity around 45 %. Rapid on-site evaluation (ROSE) is widely used for endoscopic ultrasound-acquired cytological specimen adequacy, improving its sensitivity and specificity. Nevertheless, no study has evaluated its role for ERCP-guided brushing. Our aim was to assess the diagnostic yield of ERCP-guided brushing of biliary strictures when supported by ROSE. Patients and methods This was a retrospective single-center study that included patients undergoing ERCP-guided brush cytology supported by ROSE for biliary strictures. Recorded data included patient clinical-radiological and ERCP features. Final diagnosis was determined after surgery, intraductal biopsy or adequate follow-up. The diagnostic yield was calculated and a subgroup analysis for factors associated with false-negative or true-positive results was performed. Results Two hundred six patients were included, 57.3 % males, median age 72 years, 77.2 % having extrahepatic biliary strictures. Of the patients, 99 % had an adequate sample at ROSE after a mean of 2.6 passages. The diagnostic yield was accuracy 83 %, sensitivity 74.6 %, and specificity 98 %, positive and negative predictive values 98 % and 71 % respectively, with an area under the curve of 0.86. A diagnosis of cholangiocarcinoma was significantly more frequent among true-positive cases (68 % vs 46.8 %; P = 0.04). Conclusions This is the first study evaluating the use of ROSE as support for ERCP-guided brushing of biliary strictures, with a sensitivity far higher than those reported for brushing alone and at least comparable to those of more expensive and invasive techniques.

Background: Hypertriglyceridemia (HTG) is considered within the top 5 etiologies in acute pancreatitis (AP), but the association of serum triglyceride (TG) levels with the clinical course of AP remains controversial. Objectives: This study aims to examine the effect of TG levels on severity of AP. Methods: Patients were enrolled prospectively through APPRENTICE. High TG levels were defined based on the Endocrine Society Clinical Practice Guidelines. HTG was categorized as mild (serum TG levels 150–199 mg/dL), moderate (200–999 mg/dL), severe (1,000–1,999 mg/dL), and very severe (≥2,000 mg/dL). Severity of AP was based on the revised Atlanta classification criteria. Results: Early TG levels were measured in 764 subjects and found elevated in 342 (120 with mild; 176, moderate; and 46, severe/very severe HTG). Patients with increased TG levels were younger (age ≥60, 16.7 vs. 30.3%), more likely to be male (66.1 vs. 51.2%), with more frequent alcohol use (62.8 vs. 50.7%), and diabetes mellitus (30.2 vs. 12.3%; all p ≤ 0.005). Severe AP (24.9 vs. 10.0%), ICU admission (32.5 vs. 19.7%), and mortality (5.3 vs. 1.7%; all p ≤ 0.005) were more frequently seen in patients with elevated TG levels. Based on multivariable analysis, elevated TG levels were independently associated with severe AP (p < 0.05). Conclusion: This large multicenter study confirms that elevated TG levels are associated with severe disease regardless of AP etiology.

Goals The present survey from the Italian Society of Digestive Endoscopy (SIED-Societa Italiana di Endoscopia Digestiva) was aimed at reporting infection control practice and outcomes at Digestive Endoscopy Units in a high-incidence area. Background Lombardy was the Italian region with the highest coronavirus disease-2019 (COVID-19) prevalence, at the end of March 2020 accounting for 20% of all worldwide deaths. Joint Gastro-Intestinal societies released recommendations for Endoscopy Units to reduce the risk of the contagion. However, there are few data from high-prevalence areas on adherence to these recommendations and on their efficacy. Methods A survey was designed by the Lombardy section of SIED to analyze (a) changes in activity and organization, (b) adherence to recommendations, (c) rate of health care professionals' (HCP) infection during the COVID-19 outbreak. Results In total, 35/61 invited centers (57.4%) participated; most modified activities were according to recommendations and had filtering face piece 2/filtering face piece 3 and water-repellent gowns available, but few had negative-pressure rooms or provided telephonic follow-up; 15% of HCPs called in sick and 6% had confirmed COVID-19. There was a trend (P=0.07) toward different confirmed COVID-19 rates among endoscopists (7.9%), nurses (6.6%), intermediate-care technicians (3.4%), and administrative personnel (2.2%). There was no correlation between the rate of sick HCPs and COVID-19 incidence in the provinces and personal protective equipment availability and use, whereas an inverse correlation with hospital volume was found. Conclusions Adherence to recommendations was rather good, though a minority were able to follow all recommendations. Confirmed COVID-19 seemed higher among endoscopists and nurses, suggesting that activities in the endoscopy rooms are at considerable viral spread risk.

BACKGROUND: Most pancreatic ductal adenocarcinoma patients present with advanced disease. Whether it is possible to increase survival by earlier diagnosis is unclear. OBJECTIVE: The purpose of this study was to investigate the association between presenting complaints and risk factors for pancreatic cancer with diagnostic delay, stage and survival. METHODS: This was a single-centre retrospective cohort study. Consecutive patients were interviewed and data on demographics, medical history, risk factors and complaints leading to pancreatic ductal adenocarcinoma diagnosis and disease stage were recorded. Diagnostic delay was considered as time between first complaint and diagnosis. Patients received appropriate treatments and their outcome was recorded in a dedicated database. The Chi-square test for comparison of categorical variables and the Mann–Whitney test for continuous variables were employed with Bonferroni corrections. Correlation between continuous variables was evaluated by means of the Spearman correlation coefficient. Survival analysis was performed with the Kaplan–Meier method and a log-rank test. RESULTS: The median diagnostic delay for 477 pancreatic ductal adenocarcinoma patients was two months (interquartile range 1–5), being significantly shorter for patients presenting with jaundice compared with those with pain, weight loss, diabetes (p 25 kg/m(2). The median survival time was seven months. Factors associated with worse survival at the multivariable analysis were older age (hazard ratio 1.02 per year), metastatic disease (hazard ratio 2.12) and pain as presenting complaint (hazard ratio 1.32), while diagnostic delay was not. CONCLUSION: While some complaints are associated with a shorter diagnostic delay and less advanced disease stage, we could not demonstrate that delay is associated with survival, possibly suggesting that prevention rather than early recognition is important to tackle pancreatic cancer lethality.

BACKGROUND & AIMS: The aims of this study were to: (1) assess the performance of the Pancreatitis Activity Scoring System (PASS) in a large intercontinental cohort of patients with acute pancreatitis (AP); and (2) investigate whether a modified PASS (mPASS) yields a similar predictive accuracy and produces distinct early trajectories between severity subgroups. METHODS: Data was prospectively collected through the Acute Pancreatitis Patient Registry to Examine Novel Therapies In Clinical Experience (APPRENTICE) consortium (2015-2018) involving 22 centers from 4 continents. AP severity was categorized per the revised Atlanta classification. PASS trajectories were compared between the three severity groups using the generalized estimating equations model. Four mPASS models were generated by modifying the morphine equivalent dose (MED), and their trajectories were compared. RESULTS: A total of 1393 subjects were enrolled (median age, 49 years; 51% males). The study cohort included 950 mild (68.2%), 315 (22.6%) moderately severe, and 128 (9.2%) severe AP. Mild cases had the lowest PASS at each study time point (all P < .001). A subset of patients with outlier admission PASS values was identified. In the outlier group, 70% of the PASS variation was attributed to the MED, and 66% of these patients were from the United States centers. Among the 4 modified models, the mPASS-1 (excluding MED from PASS) demonstrated high performance in predicting severe AP with an area under the receiver operating characteristic curve of 0.88 (vs area under the receiver operating characteristic of 0.83 in conventional PASS) and produced distinct trajectories with distinct slopes between severity subgroups (all P < .001). CONCLUSION: We propose a modified model by removing the MED component, which is easier to calculate, predicts accurately severe AP, and maintains significantly distinct early trajectories.

BACKGROUND/OBJECTIVES: The relationship between pre-existing diabetes mellitus (DM) and acute pancreatitis (AP) severity has not been established. We assessed the impact of pre-existing DM on AP severity in an international, prospectively ascertained registry. METHODS: APPRENTICE registry prospectively enrolled 1543 AP patients from 22 centers across 4 continents (8 US, 6 Europe, 5 Latin America, 3 India) between 2015 and 2018, and collected detailed clinical information. Pre-existing DM was defined a diagnosis of DM prior to AP admission. The primary outcome was AP severity defined by the Revised Atlanta Classification (RAC). Secondary outcomes were development of systemic inflammatory response syndrome (SIRS) or intensive care unit (ICU) admission. RESULTS: Pre-existing DM was present in 270 (17.5%) AP patients, of whom 252 (93.3%) had type 2 DM. Patients with pre-existing DM were significantly (p

The School of Athens is a XVI century fresco by Raphael, representing all the greatest minds gathered together, sharing their knowledge and discussing ideas. UEGWeek differs from it as it gathers not only the greatest minds, but also those who long to become one and learn from the others (Figure 1). Open in a separate window FIGURE 1 The UEGWeek meeting resembled as a modern School of Athens

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 Endoscopic ultrasound (EUS)-guided tissue sampling is the standard of care for diagnosing solid pancreatic lesions. While many two-way comparisons between needle types have been made in randomized controlled trials (RCTs), it is unclear which size and type of needle offers the best probability of diagnosis. We therefore performed a network meta-analysis (NMA) to compare different sized and shaped needles to rank the diagnostic performance of each needle. Methods We searched MEDLINE, EMBASE and Cochrane Library databases through August, 2020 for RCTs that compared the diagnostic accuracy of EUS fine-needle aspiration (FNA) and biopsy (FNB) needles in solid pancreatic masses. Using a random-effects NMA under the frequentist framework, RCTs were analyzed to identify the best needle type and sampling technique. Performance scores (P-scores) were used to rank the different needles based on pooled diagnostic accuracy. The NMA model was used to calculate pairwise relative risk (RR) with 95 % confidence intervals. Results Review of 2577 studies yielded 29 RCTs for quantitative synthesis, comparing 13 different needle types. All 22G FNB needles had an RR > 1 compared to the reference 22G FNA (Cook) needle. The highest P-scores were seen with the 22G Medtronic FNB needle (0.9279), followed by the 22G Olympus FNB needle (0.8962) and the 22G Boston Scientific FNB needle (0.8739). Diagnostic accuracy was not significantly different between needles with or without suction. Conclusions In comparison to FNA needles, FNB needles offer the highest diagnostic performance in sampling pancreatic masses, particularly with 22G FNB needles.

Rare truncating BRCA2 K3326X (rs11571833) and pathogenic CHEK2 I157T (rs17879961) variants have previously been implicated in familial pancreatic ductal adenocarcinoma (PDAC), but not in sporadic cases. The effect of both mutations in important DNA repair genes on sporadic PDAC risk may shed light on the genetic architecture of this disease. Both mutations were genotyped in germline DNA from 2,935 sporadic PDAC cases and 5,626 control subjects within the PANcreatic Disease ReseArch (PANDoRA) consortium. Risk estimates were evaluated using multivariate unconditional logistic regression with adjustment for possible confounders such as sex, age and country of origin. Statistical analyses were two-sided with p values

Telomere deregulation is a hallmark of cancer. Telomere length measured in lymphocytes (LTL) has been shown to be a risk marker for several cancers. For pancreatic ductal adenocarcinoma (PDAC) consensus is lacking whether risk is associated with long or short telomeres. Mendelian randomization approaches have shown that a score built from SNPs associated with LTL could be used as a robust risk marker. We explored this approach in a large scale study within the PANcreatic Disease ReseArch (PANDoRA) consortium. We analyzed 10 SNPs (ZNF676-rs409627, TERT-rs2736100, CTC1-rs3027234, DHX35-rs6028466, PXK-rs6772228, NAF1-rs7675998, ZNF208-rs8105767, OBFC1-rs9420907, ACYP2-rs11125529 and TERC-rs10936599) alone and combined in a LTL genetic score ("teloscore", which explains 2.2% of the telomere variability) in relation to PDAC risk in 2,374 cases and 4,326 controls. We identified several associations with PDAC risk, among which the strongest were with the TERT-rs2736100 SNP (OR = 1.54; 95%CI 1.35-1.76; p = 1.54 × 10-10 ) and a novel one with the NAF1-rs7675998 SNP (OR = 0.80; 95%CI 0.73-0.88; p = 1.87 × 10-6 , ptrend = 3.27 × 10-7 ). The association of short LTL, measured by the teloscore, with PDAC risk reached genome-wide significance (p = 2.98 × 10-9 for highest vs. lowest quintile; p = 1.82 × 10-10 as a continuous variable). In conclusion, we present a novel genome-wide candidate SNP for PDAC risk (TERT-rs2736100), a completely new signal (NAF1-rs7675998) approaching genome-wide significance and we report a strong association between the teloscore and risk of pancreatic cancer, suggesting that telomeres are a potential risk factor for pancreatic cancer.

Many risk factors for pancreatic cancer are related with microbiome alteration. In the past few years, the human microbiome and its relation with the immune system have been linked with carcinogenesis of different organs distant from the gut, including the pancreas. Patterns of oral microbiome associated with periodontitis are associated with an increased risk of pancreatic cancer, possibly because of the increased systemic inflammatory response, or to the capacity of some specific bacteria to alter the host immune response, making it more favorable to cancer cells. Helicobacter pylori infection when affecting the gastric body mucosa with subsequent hypochlorhydria also seems associated with an increased risk of pancreatic cancer. The composition of the intestinal microbiome is different in animal models and in humans with pancreatic cancer who have a distinct microbiome population compared with controls. Some specific bacteria can migrate from the intestine to the pancreas, and their ablation restores the immune system activity through its reprogramming with a switch toward a Th1 response and displays a protective effect toward tumor growth. More research in this area might lead to progress in terms of pancreatic cancer prevention and treatment, possibly in association with immunotherapy.

Background and study aims Feasibility of EUS-guided choledochoduodenostomy (EUS-CDS) using available lumen-apposing stents (LAMS) is limited by the size of the common bile duct (CBD) (≤ 12 mm, cut-off for experts; 15 mm, cut-off for non-experts). We aimed to assess the prevalence and predictive factors associated with CBD size ≥ 12 and 15 mm in naïve patients with malignant distal biliary obstruction (MDBO). Patients and methods This was a prospective cohort study involving 22 centers with assessment of CBD diameter and subjective feasibility of the EUS-CDS performance in naïve jaundiced patients undergoing EUS evaluation for MDBO. Results A total of 491 patients (mean age 69 ± 12 years) with mean serum bilirubin of 12.7 ± 6.6 mg/dL entered the final analysis. Dilation of the CBD ≥ 12 and 15 mm was detected in 78.8 % and 51.9 % of cases, respectively. Subjective feasibility of EUS-CDS was expressed by endosonographers in 91.2 % for a CBD ≥ 12 mm and in 96.5 % for a CBD ≥ 15 mm. On multivariate analysis, age (P Conclusions Our study showed that at presentation in a large cohort of patients with MDBO, EUS-CDS can be potentially performed in three quarters to half of cases by expert and less experienced endosonographers, respectively. Dedicated stents or devices with different designs able to overcome the limitations of existing electrocautery-enhanced LAMS for EUS-CDS are needed.

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers. Its poor prognosis is predominantly due to the fact that most patients remain asymptomatic until the disease reaches an advanced stage, alongside the lack of early markers and screening strategies. A better understanding of PDAC risk factors is essential for the identification of groups at high risk in the population. Genome-wide association studies (GWAS) have been a powerful tool for detecting genetic variants associated with complex traits, including pancreatic cancer. By exploiting functional and GWAS data, we investigated the associations between polymorphisms affecting gene function in the pancreas (expression quantitative trait loci, eQTLs) and PDAC risk. In a two-phase approach, we analysed 13 713 PDAC cases and 43 784 controls and identified a genome-wide significant association between the A allele of the rs2035875 polymorphism and increased PDAC risk (P = 7.14 × 10−10). This allele is known to be associated with increased expression in the pancreas of the keratin genes KRT8 and KRT18, whose increased levels have been reported to correlate with various tumour cell characteristics. Additionally, the A allele of the rs789744 variant was associated with decreased risk of developing PDAC (P = 3.56 × 10–6). This single nucleotide polymorphism is situated in the SRGAP1 gene and the A allele is associated with higher expression of the gene, which in turn inactivates the cyclin-dependent protein 42 (CDC42) gene expression, thus decreasing the risk of PDAC. In conclusion, we present here a functional-based novel PDAC risk locus and an additional strong candidate supported by significant associations and plausible biological mechanisms.

Background: The mitochondrial metabolism has been associated with pancreatic ductal adenocarcinoma (PDAC) risk. Recent evidence also suggests the involvement of the genetic variability of the mitochondrial function in several traits involved in PDAC etiology. However, a systematic investigation of the genetic variability of mitochondrial genome (mtSNP) and of all the nuclear genes involved in its functioning (n-mtSNPs) has never been reported. Methods: We conducted a two-phase association study of mtSNPs and n-mtSNPs to assess their effect on PDAC risk. We analyzed 35,297 n-mtSNPs and 101 mtSNPs in up to 55,870 individuals (12,884 PDAC cases and 42,986 controls). In addition, we also conducted a gene-based analysis on 1,588 genes involved in mitochondrial metabolism using Multi-marker Analysis of GenoMic Annotation (MAGMA) software. Results: In the discovery phase, we identified 49 n-mtSNPs and no mtSNPs associated with PDAC risk (P < 0.05). In the second phase, none of the findings were replicated. In the gene-level analysis, we observed that three genes (TERT, SUGCT, and SURF1) involved in the mitochondrial metabolism showed an association below the Bonferroni-corrected threshold of statistical significance (P = 0.05/1588 = 3.1 × 10−5). Conclusions: Even though the mitochondrial metabolism might be involved in PDAC etiology, our results, obtained in a study with one of the largest sample sizes to date, show that neither n-mtSNPs nor mtSNPs are associated with PDAC risk. Impact: This large case–control study does not support a role of the genetic variability of the mitochondrial function in PDAC risk.

Background and study aims Endoscopic ultrasound (EUS)-guided ablation of pancreatic ductal adenocarcinoma (PDAC) with HybridTherm-Probe (EUS-HTP) is feasible and safe, but the radiological response and ideal tool to measure it have not been investigated yet. The aims of this study were to: 1) assess the radiological response to EUS-HTP evaluating the vital tumor volume reduction rate, Response Evaluation Criteria in Solid Tumors (RECIST1.1) and Choi criteria; 2) determine the prognostic predictive yield of these criteria. Patients and methods A retrospective analysis was performed of patients with locally advanced PDAC after primary treatment or unfit for chemotherapy prospectively treated by EUS-HTP. Computed tomography scan was performed 1 month after EUS-HTP to evaluate: 1) vital tumor volume reduction rate (VTVRR) by measuring necrosis and tumor volumes through a computer-aided detection system; and 2) RECIST1.1 and Choi criteria. Results EUS-HTP was feasible in 22 of 31 patients (71 %), with no severe adverse events. Median post-HTP survival was 7 months (1 – 35). Compared to pre-HTP tumor volume, a significant 1-month VTVRR (mean 21.4 %) was observed after EUS-HTP (P = 0.005). We identified through ROC analysis a VTVRR > 11.46 % as the best cut-off to determine post-HTP 6-month survival outcome (AUC = 0.733; sensitivity = 70.0 %, specificity = 83.3 %). This cut-off was significantly associated with longer overall survival (HR = 0.372; P = 0.039). According to RECIST1.1 and Choi criteria, good responders to EUS-HTP were 60 % and 46.7 %, respectively. Good responders according to Choi, but not to RECIST1.1, had longer survival (HR = 0.407; P = 0.04). Conclusions EUS-HTP induces a significant 1-month VTVRR. This effect is assessed accurately by evaluation of necrosis and tumor volumes. Use of VTVRR and Choi criteria, but not RECIST 1.1 criteria, might identify patients who could benefit clinically from EUS-HTP.

Background and study aims Current ESGE guidelines suggest employing the suction (SU) technique for endoscopic ultrasound (EUS)-guided sampling of pancreatic solid lesions. Nonetheless, recent randomized controlled trials (RCT) have reported that the slow-pull (SP) technique has similar diagnostic accuracy with possibly less blood contamination. However, these results are heterogeneous and limited to small cohorts. The aim of this meta-analysis was to compare adequacy, accuracy, sensitivity and specificity of the SU and SP techniques for EUS-guided sampling of solid pancreatic lesions. Methods A computerized bibliographic search was restricted to RCTs. Pooled effects were calculated using a random-effects model and expressed in terms of pooled sensitivity and specificity and OR (95 % CI) for adequacy and accuracy. Results Overall, seven RCTs were included, for a total of 475 patients (163 lesions sampled with SU, 164 with SP and 148 by both). The adequacy was similar (OR = 0.98) without heterogeneity (I2 = 0 %), but a high degree of blood contamination was more common with SU than SP (pooled rate 27.6 % vs 19.7 %). A non-significant superiority of SP in terms of pooled accuracy (OR = 0.82; 95 % CI 0.36–1.85) was recorded, with moderate heterogeneity (I2 = 52.4 %). The SP technique showed a slightly higher pooled sensitivity compared to SU (88.7 % vs 83.4 %), while specificity was similar (97.2 % SP vs 96.9 % SU), with considerable heterogeneity. Conclusion The current meta-analysis reveals non-superiority of SU over SP, while SP results in reduced blood contamination. If the 5 % accuracy difference favouring SP is true, with alfa error = 0.05 and beta = 0.20, a RCT of 982 patients per arm is needed to confirm significance.

Background /Objectives: Pancreatic ductal adenocarcinoma (PDAC) has a higher incidence in men compared to women, although the difference in known risk factors cannot explain this disparity completely. Reproductive and hormonal factors have been demonstrated in pre-clinical studies to influence pancreatic carcinogenesis, but the few published data on the topic are inconsistent. The aim was to investigate the role of reproductive and hormonal factors on PDAC occurrence in women. Methods We conducted a unicenter case-control study; PDAC cases were matched to controls by age with a 1:2 ratio. Risk factors were screened through questionnaires about gynecologic and medical history. Comparisons were made using Chi-square and Fisher’s exact tests where appropriate for categorical variables and Student’s t-test for continuous variables. Logistic regression was used to calculate Odds Ratios (ORs) and their 95% confidence intervals (CI). Multivariable logistic regression models were adjusted for potential confounders. Results 253 PDAC and 506 matched controls were enrolled. At logistic regression multivariable analysis adjusted for confounding factors, older age at menopause (OR:0.95 per year; 95% CI:0.91–0.98; p = 0.007), use of Oral Contraceptives (OR:0.52; 95% CI:0.30–0.89; p = 0.018), use of Hormonal Replacement Therapy (OR:0.31; 95% CI:0.15–0.64; p = 0.001), and having had two children (OR:0.57; 95% CI:0.38–0.84; p = 0.005) were significant, independent protective factors for the onset of PDAC. Conclusions These data confirm some previous findings on menopause age and number of births while, to our knowledge, this is the first study to show a protective effect of HRT and OC use. The results collectively support the hypothesis that exposure to estrogens plays a protective role towards PDAC.

Objectives Acute pancreatitis (AP) is a sudden onset, rapidly evolving inflammatory response with systemic inflammation and multiorgan failure (MOF) in a subset of patients. New highly accurate clinical decision support tools are needed to allow local doctors to provide expert care. Methods Ariel Dynamic Acute Pancreatitis Tracker (ADAPT) is a digital tool to guide physicians in ordering standard tests, evaluate test results and model progression using available data, propose emergent therapies. The accuracy of the severity score calculators was tested using 2 prospectively ascertained Acute Pancreatitis Patient Registry to Examine Novel Therapies in Clinical Experience cohorts (pilot University of Pittsburgh Medical Center, n = 163; international, n = 1544). Results The ADAPT and post hoc expert-calculated AP severity scores were 100% concordant in both pilot and international cohorts. High-risk criteria of all 4 severity scores at admission were associated with moderately-severe or severe AP and MOF (both P < 0.0001) and prediction of no MOF was 97.8% to 98.9%. The positive predictive value for MOF was 7.5% to 14.9%. Conclusions The ADAPT tool showed 100% accuracy with AP predictive metrics. Prospective evaluation of ADAPT features is needed to determine if additional data can accurately predict and mitigate severe AP and MOF.

Objectives: Post-endoscopic retrograde cholangiopancreatography (ERCP) acute pancreatitis (PEP) is a frequent complication of this endoscopic procedure. Chronic statin intake has been linked to lower incidence and severity of acute pancreatitis (AP). Periprocedural rectal administration of non-steroidal anti-inflammatory drugs is protective against PEP, but the role of chronic acetylsalicylic acid (ASA) treatment is unclear. We aimed to investigate whether statins and chronic ASA intake are associated with lower risk of PEP. Methods: An international, multicenter, prospective cohort study. Consecutive patients undergoing ERCP in seven European centers were included. Patients were followed-up to detect those with PEP. Multivariate analysis by means of binary logistic regression was performed, and adjusted odds ratios (aORs) were calculated. Results: A total of 1150 patients were included, and 70 (6.1%) patients developed PEP. Among statins users, 8.1% developed PEP vs. 5.4% among non-users (P=0.09). Multivariate analysis showed no association between statin use and PEP incidence (aOR 1.68 (95% CI 0.94–2.99, P=0.08)). Statin use had no effect on severity of PEP, being mild in 92.0% of statin users vs. 82.2% in non-statin users (P=0.31). Chronic ASA use was not associated with PEP either (aOR 1.02 (95% CI 0.49–2.13), P=0.96). Abuse of alcohol and previous endoscopic biliary sphincterotomy were protective factors against PEP, while >1 pancreatic guidewire passage, normal bilirubin values, and duration of the procedure >20minutes, were risk factors. Conclusions: The use of statins or ASA is not associated with a lower risk or a milder course of PEP.

BackgroundMost cases of pancreatic ductal adenocarcinoma (PDAC) are asymptomatic in early stages, and the disease is typically diagnosed in advanced phases, resulting in very high mortality. Tools to identify individuals at high risk of developing PDAC would be useful to improve chances of early detection.ObjectiveWe generated a polygenic risk score (PRS) for PDAC risk prediction, combining the effect of known risk SNPs, and carried out an exploratory analysis of a multifactorial score.MethodsWe tested the associations of the individual known risk SNPs on up to 2851 PDAC cases and 4810 controls of European origin from the PANcreatic Disease ReseArch (PANDoRA) consortium. Thirty risk SNPs were included in a PRS, which was computed on the subset of subjects that had 100% call rate, consisting of 839 cases and 2040 controls in PANDoRA and 6420 cases and 4889 controls from the previously published Pancreatic Cancer Cohort Consortium I–III and Pancreatic Cancer Case-Control Consortium genome-wide association studies. Additional exploratory multifactorial scores were constructed by complementing the genetic score with smoking and diabetes.ResultsThe scores were associated with increased PDAC risk and reached high statistical significance (OR=2.70, 95% CI 1.99 to 3.68, p=2.54×10−10 highest vs lowest quintile of the weighted PRS, and OR=14.37, 95% CI 5.57 to 37.09, p=3.64×10−8, highest vs lowest quintile of the weighted multifactorial score).ConclusionWe found a highly significant association between a PRS and PDAC risk, which explains more than individual SNPs and is a step forward in the direction of the construction of a tool for risk stratification in the population.

Early onset pancreatic cancer (EOPC) is a rare disease with a very high mortality rate. Almost nothing is known on the genetic susceptibility of EOPC, therefore we performed a genome-wide association study (GWAS) to identify novel genetic variants specific for patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) at younger ages. In the first phase, conducted on 821 cases with age of onset ≤60 years, of whom 198 with age of onset ≤50, and 3227 controls from PanScan I-II, we observed four SNPs (rs7155613, rs2328991, rs4891017 and rs12610094) showing an association with EOPC risk (P < 1x10-4 ). We replicated these SNPs in the PANcreatic Disease ReseArch (PANDoRA) consortium and used additional in silico data from PanScan III and PanC4. Among these four variants rs2328991 was significant in an independent set of 855 cases with age of onset ≤60 years, of whom 265 with age of onset≤50, and 4142 controls from the PANDoRA consortium while in the in silico data we observed no statistically significant association. However, the resulting meta-analysis supported the association (P = 1.15x10-4 ). In conclusion we propose a novel variant rs2328991 to be involved in EOPC risk. Even though it was not possible to find a mechanistic link between the variant and the function, the association is supported by a solid statistical significance obtained in the largest study on EOPC genetics present so far in the literature. This article is protected by copyright. All rights reserved.

Transcriptome analyses allow the distinguishing of pancreatic ductal adenocarcinoma (PDAC) subtypes, exhibiting different prognoses and chemotherapy responses. However, RNA extraction from pancreatic tissue is cumbersome and has been performed mainly from surgical samples, which are representative of &lt, 20% of cases. The majority of PDAC patients undergo endoscopic ultrasound (EUS)-guided tissue acquisition (EUS-TA), but RNA has been rarely extracted from EUS-TA with scanty results. Herein, we aimed to determine the best conditions for RNA extraction and analysis from PDAC EUS-TA samples in order to carry out molecular analyses. PDAC cases underwent diagnostic EUS-TA, with needles being a 25G fine needle aspiration (FNA) in all patients and then either a 20G lateral core-trap fine needle biopsy (FNB) or a 25G Franseen FNB, the conservation methods were either snap freezing, RNALater or Trizol. RNA concentration and quality (RNA integrity index, RIN) were analyzed and a panel of genes was investigated for tissue contamination and markers of molecular subtype and aggressivity through qRT-PCR. Seventy-four samples from 37 patients were collected. The median RNA concentration was significantly higher in Trizol samples (10.33 ng/uL) compared with snap frozen (0.64 ng/uL, p &lt, 0.0001) and RNALater (0.19 ng/uL, 0.0001). The RIN was similar between Trizol (5.15) and snap frozen samples (5.85), while for both methods it was higher compared with RNALater (2.7). Among the needles, no substantial difference was seen in terms of RNA concentration and quality. qRT-PCR analyses revealed that samples from all needles were suitable for the detection of PDAC subtype markers (GATA6 and ZEB1) and splice variants associated with mutational status (GAP17) as well as for the detection of contaminating tissue around PDAC cells. This is the first study that specifically investigates the best methodology for RNA extraction from EUS-TA. A higher amount of good quality RNA is obtainable with conservation in Trizol with a clear superiority of neither FNA nor FNB needles. RNA samples from EUS-TA are suitable for transcriptome analysis including the investigation of molecular subtype and splice variants expression.

The development of devices applied to endoscopy has led endoscopic ultrasound (EUS) to become also an interventional procedure, for example with EUS-guided direct tumor ablation that can represent a potential therapeutic alternative option for patients not amenable to surgical treatments. Great efforts have been made to develop EUS-guided ablative therapy for pancreatic cancer, with the aim of providing better local disease control and reduce metastatic tumor spreading. This review will provide a description of the different EUS-guided ablative technologies and their clinical application.

EUS diagnostic puncture has been performed for over 25 years, impressively evolving with the development of new techniques and devices. In this era when tumors are on the rise and giving the necessity of minimally invasive procedures, EUS has a key role for the diagnosis of lesions arising anywhere near the GI wall. It is currently performed as a routine procedure for outpatients in many instances and is being increasingly used to give an accurate diagnosis with a very low risk of side effects.

Background: Statins are perceived as potential etiological factors for acute pancreatitis (AP), but recent evidence suggests the opposite. Our aim was to evaluate the association between statin use and risk of AP in observational studies. Methods: Medline, Scopus, and Web of Science were searched for cohort (C) and case-control (CC) studies evaluating statins as intervention and AP as outcome. Pooled adjusted odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated. Results: Thirteen studies (seven CC, six C) with 34,899 AP patients and 5,377,894 controls were included. Prevalence of statin use was 9.8% among AP patients and 25% among controls. Pooled adjusted OR was 1.00 (95% CI = 0.63 to 1.59) with considerable heterogeneity (I-2 = 98%). CC studies were associated with increased AP risk (OR = 1.33; 95% CI = 1.20 to 1.47), unlike C studies (OR = 0.69; 95% CI = 0.37 to 1.31). No association with increased risk was found for studies from Western countries (OR = 0.90; 95% CI = 0.52 to 1.56), unlike for studies conducted in Asia (OR = 1.39; 95% CI = 1.10 to 1.75). Conclusion: Statin use is not associated with increased risk of AP. Increased risk was limited to CC studies, which are more prone to bias, while C studies showed no global effect. Further research is needed to clarify whether statin type, dosage, treatment duration or AP etiology might account for this difference.

Background Hospitalization and death in patients with chronic pancreatitis (CP) are often due to extra-pancreatic events. Recent guidelines recommend the use of the MUST score to assess CP patients’ nutritional status, but its association with clinical outcomes has been poorly investigated. The aims of this study are to evaluate the incidence of extra-pancreatic events in patients with CP during follow-up and their association with the nutritional status. Methods Retrospective analysis of single-centre cohort of CP patients prospectively enrolled and followed-up. Exocrine pancreatic insufficiency (EPI) was assessed by fecal elastase, MUST score calculated at diagnosis. The occurrence of hospitalizations or death were recorded. Differences between subgroups were analysed by Fisher’s and T-test and hospitalization-free survival with Kaplan-Meier curves and Cox regression analysis. Results Of 111 enrolled patients (64% male; mean age 57); 52% had alcoholic aetiology, 53% EPI, 10% severe CP and 26% a MUST score≥2 at diagnosis. During a median follow-up of 37 months, 3.6% of patients died and 34.2% needed hospitalization, in 50% of cases for extrapancreatic events (2% cardiovascular events, 8% infections and 3% cancer). There was no significant association between EPI, BMI Conclusions A sizeable portion of CP patients are at high risk of malnutrition and are hospitalized during the follow-up, often for extra-pancreatic events. The nutritional status evaluated with the MUST score lacks accuracy in predicting the risk of these events.

Background The aim of the study was to evaluate the current opinion and clinical decision-making process of international pancreatologists, and to systematically identify key study questions regarding the diagnosis and treatment of chronic pancreatitis (CP) for future research. Methods An online survey, including questions regarding the diagnosis and treatment of CP and several controversial clinical case vignettes, was send by e-mail to members of various international pancreatic associations: IHPBA, APA, EPC, ESGE and DPSG. Results A total of 288 pancreatologists, 56% surgeons and 44% gastroenterologists, from at least 47 countries, participated in the survey. About half (48%) of the specialists used a classification tool for the diagnosis of CP, including the Mayo Clinic (28%), Mannheim (25%), or Buchler (25%) tools. Overall, CT was the preferred imaging modality for evaluation of an enlarged pancreatic head (59%), pseudocyst (55%), calcifications (75%), and peripancreatic fat infiltration (68%). MRI was preferred for assessment of main pancreatic duct (MPD) abnormalities (60%). Total pancreatectomy with auto-islet transplantation was the preferred treatment in patients with parenchymal calcifications without MPD abnormalities and in patients with refractory pain despite maximal medical, endoscopic, and surgical treatment. In patients with an enlarged pancreatic head, 58% preferred initial surgery (PPPD) versus 42% initial endoscopy. In patients with a dilated MPD and intraductal stones 56% preferred initial endoscopic ± ESWL treatment and 29% preferred initial surgical treatment. Conclusion Worldwide, clinical decision-making in CP is largely based on local expertise, beliefs and disbeliefs. Further development of evidence-based guidelines based on well designed (randomized) studies is strongly encouraged.

Background Data on chronic pancreatitis prevalence are scanty and usually limited to hospital-based studies. Aim Investigating chronic pancreatitis prevalence in primary care. Methods Participating primary care physicians reported the prevalence of chronic pancreatitis among their registered patients, environmental factors and disease characteristics. The data were centrally reviewed and chronic pancreatitis cases defined according to M-ANNHEIM criteria for diagnosis and severity and TIGAR-O classification for etiology. Results Twenty-three primary care physicians participated in the study. According to their judgment, 51 of 36.401 patients had chronic pancreatitis. After reviewing each patient data, 11 turned out to have definite, 5 probable, 19 borderline and 16 uncertain disease. Prevalence was 30.2/100.000 for definite cases and 44.0/100.000 for definite plus probable cases. Of the 16 patients with definite/probable diagnosis, 8 were male, with mean age of 55.6 (±16.7). Four patients had alcoholic etiology, 5 post-acute/recurrent pancreatitis, 6 were deemed to be idiopathic. Four had pancreatic exocrine insufficiency, 10 were receiving pancreatic enzymes, and six had pain. Most patients had initial stage and non-severe disease. Conclusions This is the first study investigating the prevalence of chronic pancreatitis in primary care. Results suggest that the prevalence in this context is higher than in hospital-based studies, with specific features, possibly representing an earlier disease stage.