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Background: Early-onset pancreatic cancer (EOPC) represents 5–10% of all pancreatic ductal adenocarcinoma (PDAC) cases, and the etiology of this form is poorly understood. It is not clear if established PDAC risk factors have the same relevance for younger patients. This study aims to identify genetic and non-genetic risk factors specific to EOPC. Methods: A genome-wide association study was performed, analysing 912 EOPC cases and 10 222 controls, divided into discovery and replication phases. Furthermore, the associations between a polygenic risk score (PRS), smoking, alcohol consumption, type 2 diabetes and PDAC risk were also assessed. Results: Six novel SNPs were associated with EOPC risk in the discovery phase, but not in the replication phase. The PRS, smoking, and diabetes affected EOPC risk. The OR comparing current smokers to never-smokers was 2.92 (95% CI 1.69–5.04, P = 1.44 × 10−4). For diabetes, the corresponding OR was 14.95 (95% CI 3.41–65.50, P = 3.58 × 10−4). Conclusion: In conclusion, we did not identify novel genetic variants associated specifically with EOPC, and we found that established PDAC risk variants do not have a strong age-dependent effect. Furthermore, we add to the evidence pointing to the role of smoking and diabetes in EOPC.

Pancreatic cancer has an incidence that almost matches its mortality. Only a small number of risk factors and 33 susceptibility loci have been identified. so Moreover, the relative rarity of pancreatic cancer poses significant hurdles for research aimed at increasing our knowledge of the genetic mechanisms contributing to the disease. Additionally, the inability to adequately power research questions prevents small monocentric studies from being successful. Several consortia have been established to pursue a better understanding of the genetic architecture of pancreatic cancers. The Pancreatic disease research (PANDoRA) consortium is the largest in Europe. PANDoRA is spread across 12 European countries, Brazil and Japan, bringing together 29 basic and clinical research groups. In the last ten years, PANDoRA has contributed to the discovery of 25 susceptibility loci, a feat that will be instrumental in stratifying the population by risk and optimizing preventive strategies.

Genes carrying high-penetrance germline mutations may also be associated with cancer susceptibility through common low-penetrance genetic variants. To increase the knowledge on genetic pancreatic ductal adenocarcinoma (PDAC) aetiology, the common genetic variability of PDAC familial genes was analysed in this study. We conducted a multi-phase study analysing 7,745 single nucleotide polymorphisms (SNPs) from 29 genes reported to harbour a high-penetrance PDAC-associated mutation in at least one published study. To assess the effect of the SNPs on PDAC risk, a total of 14,666 PDAC cases and 221,897 controls across five different studies were analysed. The T allele of the rs1412832 polymorphism, that is situated in the CDKN2B-AS1/ANRIL, showed a genome-wide significant association with increased risk of developing PDAC (OR=1.11, 95%CI=1.07-1.15, P=5.25×10-9 ). CDKN2B-AS1/ANRIL is a long non-coding RNA, situated in 9p21.3, and regulates many target genes, among which CDKN2A (p16) that frequently shows deleterious somatic and germline mutations and deregulation in PDAC. Our results strongly support the role of the genetic variability of the 9p21.3 region in PDAC aetiopathogenesis and highlight the importance of secondary analysis as a tool for discovering new risk loci in complex human diseases. This article is protected by copyright. All rights reserved.

Background: Predicting Post-Endoscopic Retrograde Cholangiopancreatography (ERCP) pancreatitis (PEP) risk can be determinant in reducing its incidence and managing patients appropriately, however studies conducted thus far have identified single-risk factors with standard statistical approaches and limited accuracy. Aim: To build and evaluate performances of machine learning (ML) models to predict PEP probability and identify relevant features. Methods: A proof-of-concept study was performed on ML application on an international, multicenter, prospective cohort of ERCP patients. Data were split in training and test set, models used were gradient boosting (GB) and logistic regression (LR). A 10-split random cross-validation (CV) was applied on the training set to optimize parameters to obtain the best mean Area Under Curve (AUC). The model was re-trained on the whole training set with the best parameters and applied on test set. Shapley-Additive-exPlanation (SHAP) approach was applied to break down the model and clarify features impact. Results: One thousand one hundred and fifty patients were included, 6.1% developed PEP. GB model outperformed LR with AUC in CV of 0.7 vs 0.585 (p-value=0.012). GB AUC in test was 0.671. Most relevant features for PEP prediction were: bilirubin, age, body mass index, procedure time, previous sphincterotomy, alcohol units/day, cannulation attempts, gender, gallstones, use of Ringer's solution and periprocedural NSAIDs. Conclusion: In PEP prediction, GB significantly outperformed LR model and identified new clinical features relevant for the risk, most being pre-procedural.

The incidence of ampullary tumors is increasing but data on association with an increased exposure to certain risk factors are scanty.To investigate risk and protective factors associated with the occurrence of ampullary tumors and whether these factors differ between ampullary tumors of the intestinal and pancreatobiliary subtypes or between adenomas and carcinomas.The association between a large set of exposome features and ampullary tumors occurrence was investigated in a bi-centric case-control study after ethic committee approval and power calculation.In 223 histologically confirmed patients and 446 controls, previous cholecystectomy (odd ratio [OR] = 2.07; 95% confidence interval [CI] = 1.34-3.20) and proton pump inhibitors use (OR = 1.66; 95% CI = 1.16-2.37) were associated with increased risk of ampullary tumors, aspirin use (OR = 0.57; 95% CI = 0.36-0.90) and light alcohol intake (OR = 0.54; 95% CI = 0.38-0.76) with reduced risk. A previous cholecystectomy was also associated with tumors of intestinal subtype and with both adenomas and carcinomas, and proton pump inhibitors use with adenomas only. Smoking, body mass index, family history of cancers, previous ulcer, diabetes and use of statins, insulin and metformin were not significant factors.This is the first case-control study specifically highlighting factors associated with the occurrence of ampullary tumors. We report factors that are novel and plausible, in keeping with mechanisms described for other gastrointestinal tumors and with potential clinical relevance.

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

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.

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.

Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second cancer-related cause of death by 2030. Identifying novel risk factors, including genetic risk loci, could be instrumental in risk stratification and implementation of prevention strategies. Long noncoding RNAs (lncRNAs) are involved in regulation of key biological processes, and the possible role of their genetic variability has been unexplored so far. Combining genome wide association studies and functional data, we investigated the genetic variability in all lncRNAs. We analyzed 9893 PDAC cases and 9969 controls and identified a genome-wide significant association between the rs7046076 SNP and risk of developing PDAC (P = 9.73 × 10-9 ). This SNP is located in the NONHSAG053086.2 (lnc-SMC2-1) gene and the risk allele is predicted to disrupt the binding of the lncRNA with the micro-RNA (miRNA) hsa-mir-1256 that regulates several genes involved in cell cycle, such as CDKN2B. The CDKN2B region is pleiotropic and its genetic variants have been associated with several human diseases, possibly though an imperfect interaction between lncRNA and miRNA. We present a novel PDAC risk locus, supported by a genome-wide statistical significance and a plausible biological mechanism.

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.

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.

With recent advances in molecular pathology and the development of new chemotherapy regimens, the knowledge of the molecular alterations of pancreatic ductal adenocarcinoma (PDAC) is becoming appealing for stratifying patients for prognosis and response to a defined treatment. Archival formalin-fixed, paraffinembedded samples are a useful source of genomic deoxyribonucleic acid; nevertheless, most studies employed formalin-fixed, paraffin-embedded samples deriving from surgical specimens, which are therefore representative of

Background and study aims With common bile duct (CBD) stones, access to the CBD can be achieved through the papilla orifice followed by standard biliary sphincterotomy (SBS), or through precut fistulotomy (PF) in case of difficult cannulation. The two methods alter papilla anatomy differently, potentially leading to a different rate of stone recurrence. No data have been published on stone recurrence after PF in patients with CBD stones. The aim of this study was to evaluate CBD stone recurrence, reintervention rate after PF versus SBS, and complications. Patients and methods This was a retrospective single-center cohort study including patients undergoing for the first time endoscopic retrograde cholangiopancreatography (ERCP) for CBD stones with PF in case of failed repeated cannulation attempts, matched for sex/age to patients with SBS randomly extracted from our database. T-test and Fisher’s tests were used for continuous and categorical variable comparison. Recurrence probability was calculated with Kaplan–Meier curve. Factors associated with ERCP repetition were evaluated with logistic regression through a Cox’s proportional hazards model. Results Eighty-five patients with PF were included, with 85 matched controls (mean age 68.7 years, 45.9 % males). Overall, patients with PF had the same reintervention rate as those with SBS (14.1 % vs. 12.9 %) with a hazard ratio (HR) of 1.11 (95 % CI 0.49 – 2.50; P = 0.81), but mean time to reintervention was significantly lower (74.9 ± 74.6 vs. 765.6 ± 961.3 days; P Conclusions The reintervention rate was significantly higher in the short term after PF. Therefore, closer follow-up in the first 6 to 12 months after ERCP might be appropriate for patients underoing PF.

Background: Acute pancreatitis (AP) is the most common complication after endoscopic retrograde cholangiopancreatography (ERCP). Statins have been traditionally associated to an increased risk of AP, however, recent evidence suggests that statins may have a protective role against this disease. Aims: Our primary aim is to investigate whether the use of statins has a protective effect against post-ERCP pancreatitis (PEP). Secondary outcomes are: to evaluate the effect of other drugs on the incidence of PEP; to ascertain the relationship between the use of statins and the severity of PEP; and to evaluate the effect of other risk and protective factors on the incidence of PEP. Methods: STARK is an international multicenter prospective cohort study. Centers from Spain, Italy, Croatia, Finland and Sweden joined this study. The total sample size will include about 1016 patients, which was based on assuming a 5% incidence of PEP among non-statin (NSt) users, a 1-3 ratio of statin (St) and NSt consumers respectively, a 70% decrease in PEP among St consumers, an alpha-error of 0.05 and beta-error of 0.20. All patients aged >18 years scheduled for ERCP will be offered to enter the study. Discussion: STARK study will ascertain whether statins, a safe, widely used and inexpensive drug, can modify the incidence of PEP. (C) 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Different inflammation-based scores such as the neutrophil/lymphocyte ratio (NLR), the Odonera Prognostic Nutritional Index (PNI), the Glasgow Prognostic Score, the platelet/lymphocyte ratio, and the C-reactive protein/albumin ratio have been found to be significantly associated with pancreatic cancer (PDAC) prognosis. However, most studies have investigated patients undergoing surgery, and few of them have compared these scores. We aimed at evaluating the association between inflammatory-based scores and PDAC prognosis. In a single center cohort study, inflammatory-based scores were assessed at diagnosis and their prognostic relevance as well as that of clinic-pathological variables were evaluated through multiple logistic regression and survival probability analysis. In 206 patients, age, male sex, tumor size, presence of distant metastasis, access to chemotherapy, and an NLR > 5 but not other scores were associated with overall survival (OS) at multivariate analysis. Patients with an NLR < 5 had a median survival of 12 months compared to 4 months in those with an NLR > 5. In the 81 patients with distant metastasis at diagnosis, an NLR > 5 resulted in the only variable significantly associated with survival. Among patients with metastatic disease who received chemotherapy, the median survival was 3 months in patients with an NLR > 5 and 7 months in those with an NLR < 5. The NLR might drive therapeutic options in PDAC patients, especially in the setting of metastatic disease.

Data on the association between aspirin and statin use and Pancreatic Ductal AdenoCarcinoma (PDAC) risk are conflicting. These drugs are often co-prescribed, but no studies evaluated the potential combined or confounding effect of the two at the same time. We aimed to investigate the association between aspirin and statin exclusive and combined use and PDAC occurrence. Data on environmental factors, family and medical history were screened in a case-control study. PDAC cases were matched to controls for age and gender. Power calculation performed ahead. Odds ratios (OR) and 95% confidence intervals(CI) were obtained from multivariable logistic regression analysis. In 408 PDAC patients and 816 matched controls, overall statin (OR 0.61; 95%CI,0.43–0.88), but not aspirin use was associated to reduced PDAC risk. Compared to non-users, exclusive statin (OR 0.51; 95%CI,0.32–0.80) and exclusive aspirin users (OR 0.64; 95%CI,0.40–1.01) had reduced PDAC risk. Concomitant statin and aspirin use did not further reduce the risk compared with statin use alone and no interaction was evident. Statin protective association was dose-dependent, and consistent in most subgroups, being stronger in smokers, elderly, obese and non-diabetic patients. The present study suggests that statin use is associated to reduced PDAC risk, supporting a chemopreventive action of statins on PDAC.

Evidence on small intestinal bacterial overgrowth (SIBO) in patients with chronic pancreatitis (CP) is conflicting.The purpose of this study was to perform a systematic review and meta-analysis on the prevalence of SIBO in CP and to examine the relationship of SIBO with symptoms and nutritional status.Case-control and cross-sectional studies investigating SIBO in CP patients were analysed. The prevalence of positive tests was pooled across studies, and the rate of positivity between CP cases and controls was calculated.In nine studies containing 336 CP patients, the pooled prevalence of SIBO was 36% (95% confidence interval (CI) 17-60%) with considerable heterogeneity (One-third of CP patients have SIBO, with a significantly increased risk over controls, although results are heterogeneous, and studies carry several limitations. The impact of SIBO and its treatment in CP patients deserve further investigation.

Pancreatic neuroendocrine tumors (PNETs) are heterogeneous neoplasms which represent only 2% of all pancreatic neoplasms by incidence, but 10% by prevalence. Genetic risk factors could have an important role in the disease aetiology, however only a small number of case control studies have been performed yet. To further our knowledge, we genotyped 13 SNPs belonging to the pleiotropic CDKN2A/B gene region in 320 PNET cases and 4436 controls, the largest study on the disease so far. We observed a statistically significant association between the homozygotes for the minor allele of the rs2518719 SNP and an increased risk of developing PNET (ORhom = 2.08, 95% CI 1.05–4.11, p = 0.035). This SNP is in linkage disequilibrium with another polymorphic variant associated with increased risk of several cancer types. In silico analysis suggested that the SNP could alter the sequence recognized by the Neuron-Restrictive Silencer Factor (NRSF), whose deregulation has been associated with the development of several tumors. The mechanistic link between the allele and the disease has not been completely clarified yet but the epidemiologic evidences that link the DNA region to increased cancer risk are convincing. In conclusion, our results suggest rs2518719 as a pleiotropic CDKN2A variant associated with the risk of developing PNETs.

Background About 10% of pancreatic cancer patients are aged ≤50 at diagnosis and defined as Early Onset Pancreatic Cancer (EOPC). There is limited information regarding risk factors for EOPC occurrence and their outcome. Aim To investigate risk factors, presentation features and outcome of EOPC patients. Methods Consecutive, histologically confirmed, pancreatic cancer patients enrolled. Data regarding environmental and genetic risk factors, clinical and pathological information, treatment and survival were recorded. EOPC patients (aged ≤50 at diagnosis) were compared to older subjects. Results Twenty-five of 293 patients (8.5%) had EOPC. There was no difference regarding sex distribution, medical conditions and alcohol intake between EOPC and older subjects. EOPC patients were more frequently current smokers (56% vs 28% p = 0.001) and started smoking at a significantly lower mean age (19.8 years, 95%CI 16.7–22.9) as compared to older patients (26.1, 95%CI 24.2–28) (p = 0.001). Current smoking (OR 7.5; 95%CI 1.8–30; p = 0.004) and age at smoking initiation (OR 0.8 for every increasing year; 95%CI 0.7–0.9; p = 0.01) were significant and independent risk factors for diagnosis of EOPC. There were no differences regarding genetic syndromes and pancreatic cancer family history. EOCP presented less frequently with jaundice (16% vs 44%, p = 0.006) and had a higher rate of unresectable disease, albeit not significantly (84% vs 68%, p = 0.1). EOPC patients were more frequently fit for surgery or chemotherapy than their counterpart, resulting in similar stage-specific survival probability. Conclusion EOPC seems related to active and early smoking but not to familial syndromes. Young patients display aggressive disease but not worse outcome.

Pancreas is a doubled-entity organ, with both an exocrine and an endocrine component, reciprocally interacting in a composed system whose function is relevant for digestion, absorption, and homeostasis of nutrients. Thus, it is not surprising that disorders of the exocrine pancreas also affect the endocrine system and vice versa. It is well-known that patients with chronic pancreatitis develop a peculiar form of diabetes (type III), caused by destruction and fibrotic injury of islet cells. However, less is known on the influence of diabetes on pancreatic exocrine function. Pancreatic exocrine insufficiency (PEI) has been reported to be common in diabetics, with a prevalence widely ranging, in different studies, in both type I (25–74%) and type II (28–54%) diabetes. A long disease duration, high insulin requirement, and poor glycemic control seem to be risk factors for PEI occurrence. The impact of pancreatic exocrine replacement therapy on glycemic, insulin, and incretins profiles has not been fully elucidated. The present paper is aimed at reviewing published studies investigating the prevalence of PEI in diabetic patients and factors associated with its occurrence.