Polymorphisms within autophagy-related genes as susceptibility biomarkers for pancreatic cancer: A meta-analysis of three large European cohorts and functional characterization.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with patients having unresectable or metastatic disease at diagnosis, with poor prognosis and very short survival. Given that genetic variation within autophagy-related genes influences autophagic flux and susceptibility to solid cancers, we decided to investigate whether 55,583 single nucleotide polymorphisms (SNPs) within 234 autophagy-related genes could influence the risk of developing PDAC in three large independent cohorts of European ancestry including 12,754 PDAC cases and 324,926 controls. The meta-analysis of these populations identified, for the first time, the association of the BID variant with an increased risk of developing the disease (OR = 1.

Primary drainage of distal malignant biliary obstruction: A comparative network meta-analysis.

Background: The effectiveness of various primary upfront drainage techniques for distal malignant biliary obstructions (dMBO) is not well-established.

Objective: To compare the technical and clinical success rates and adverse event (AE) rates of various primary drainage techniques.

Methods: We systematically reviewed RCTs comparing the technical and clinical success and AE rates of EUS-choledochoduodenostomy (CDS) with lumen-apposing metal stent (LAMS), EUS-CDS with self-expandable metal stents (SEMS), EUS-hepaticogastrostomy (HGS), ERCP, and PTBD performed upfront.

Correlation between endoscopic ultrasound features and exocrine pancreatic function in chronic pancreatitis.

Background: Endoscopic ultrasound (EUS) is the most sensitive method for diagnosing chronic pancreatitis (CP) in its early stages, and Rosemont Classification (RC) is used for its evaluation. Data on the correlation between EUS features and pancreatic exocrine insufficiency (PEI) are limited. We investigated the correlation between the EUS findings and PEI.

Germline pathogenic variants of cancer predisposition genes in a multicentre Italian cohort of pancreatic cancer patients.

Background And Aim: Germline BRCA1-2 test is routinely recommended in Pancreatic Cancer (PC) patients, due to its clinical-epidemiological relevance. Data on the prevalence of germline pathogenic variants (gPV) in other cancer predisposition and DNA Damage Repair (DDR) system-related genes in unselected PC cases are sparce in Italy. We assessed this prevalence in a multicentre cohort, to derive recommendations for PC patients.

Association of Smoking with progression from low-risk to high-risk intraductal papillary mucinous neoplasms and pancreatic cancer.

Background: Factors associated with the risk of pancreatic adenocarcinoma (PDAC) may play a role in the development and progression of Intraductal Papillary Mucinous Neoplasms (IPMNs). However, data are limited.

Aim: To compare exposome factors in three groups of patients with "high or low-risk" IPMNs, as assessed at diagnosis and during a 24-months follow-up, and with PDAC.

A pleiotropy scan to discover new susceptibility loci for pancreatic ductal adenocarcinoma.

Pleiotropic variants (i.e., genetic polymorphisms influencing more than one phenotype) are often associated with cancer risk.

The Italian registry of families at risk for pancreatic cancer (IRFARPC): implementation and evolution of a national program for pancreatic cancer surveillance in high-risk individuals.

Screening programs for early detection and treatment of pancreatic cancer (PC) and its precursor lesions are increasingly implemented worldwide to reduce disease-specific lethality. Given the relatively low prevalence of the disease, the ideal target of such approaches is an enriched cohort of individuals harboring a lifetime risk of developing PC significantly higher compared to the general population, given either a substantial aggregation of PC cases in their family (i.e.

Same-session endoscopic diagnosis and symptom palliation in pancreato-biliary malignancies: Clinical impact of rapid on-site evaluation (ROSE).

Besides increasing adequacy, rapid on-site evaluation (ROSE) during endoscopic ultrasound (EUS) or endoscopic retrograde cholangiopancreatography (ERCP) may impact choices and timing of subsequent therapeutic procedures, yet has been unexplored. This was a retrospective evaluation of a prospectively maintained database of a tertiary, academic centre with availability of ROSE and hybrid EUS-ERCP suites. All consecutive patients referred for pathological confirmation of suspected malignancy and jaundice or gastric outlet obstruction (GOO) between Jan-2020 and Sep-2022 were included.

Endoscopic Management of Difficult Biliary Stones: An Evergreen Issue.

Choledocholithiasis is one of the most common indications for endoscopic retrograde cholangiopancreatography (ERCP) in daily practice. Although the majority of stones are small and can be easily removed in a single endoscopy session, approximately 10-15% of patients have complex biliary stones, requiring additional procedures for an optimum clinical outcome. A plethora of endoscopic methods is available for the removal of difficult biliary stones, including papillary large balloon dilation, mechanical lithotripsy, and electrohydraulic and laser lithotripsy.

Polymorphisms in transcription factor binding sites and enhancer regions and pancreatic ductal adenocarcinoma risk.

Genome-wide association studies (GWAS) are a powerful tool for detecting variants associated with complex traits and can help risk stratification and prevention strategies against pancreatic ductal adenocarcinoma (PDAC). However, the strict significance threshold commonly used makes it likely that many true risk loci are missed. Functional annotation of GWAS polymorphisms is a proven strategy to identify additional risk loci.

Managing complications of chronic pancreatitis: a guide for the gastroenterologist.

Introduction: Chronic pancreatitis is a heterogeneous and complex syndrome that, in most cases, causes pain as a cardinal symptom and affects both the morphology and function of the pancreas, leading to several serious complications.

Areas Covered: The present review, based on a non-systematic PubMed search updated to June 2023, aims to present the current available evidence on the role of gastroenterologists in the diagnosis and treatment of both local and systemic complications by either endoscopic or medical treatments.

Expert Opinion: At diagnosis and during chronic pancreatitis follow-up, particular care is needed to consider not only the clinically manifest signs and symptoms of the disease, such as pain, jaundice, gastrointestinal obstruction, and pseudocysts, which require multidisciplinary discussion to establish the best treatment option (endoscopic or surgical), but also less evident systemic complications.

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

Introduction: Pancreatic cancer (PC) surveillance of high-risk individuals (HRI) is becoming more common worldwide, aiming at anticipating PC diagnosis at a preclinical stage. In 2015, the Italian Registry of Families at Risk of Pancreatic Cancer was created. We aimed to assess the prevalence and incidence of pancreatic findings, oncological outcomes, and harms 7 years after the Italian Registry of Families at Risk of Pancreatic Cancer inception, focusing on individuals with at least a 3-year follow-up or developing events before.

Clinical usefulness of scoring systems to predict severe acute pancreatitis: A systematic review and meta-analysis with pre and post-test probability assessment.

Background: Scoring systems for severe acute pancreatitis (SAP) prediction should be used in conjunction with pre-test probability to establish post-test probability of SAP, but data of this kind are lacking.

Objective: To investigate the predictive value of commonly employed scoring systems and their usefulness in modifying the pre-test probability of SAP.

Methods: Following PRISMA statement and MOOSE checklists after PROSPERO registration, PubMed was searched from inception until September 2022.

Surveillance of Individuals at High Risk of Developing Pancreatic Cancer: A Prevalence Meta-analysis to Estimate the Rate of Low-yield Surgery.

Objective: To quantify the rate of low-yield surgery, defined as no high-grade dysplastic precursor lesions or T1N0M0 pancreatic cancer at pathology, during pancreatic cancer surveillance.

Background: Global efforts have been made in pancreatic cancer surveillance to anticipate the diagnosis of pancreatic cancer at an early stage and improve survival in high-risk individuals (HRIs) with a hereditary predisposition. The negative impact of pancreatic cancer surveillance when surgery is performed for low-grade dysplasia or a non-neoplastic condition is not well quantified.

A scan of all coding region variants of the human genome, identifies 13q12.2-rs9579139 and 15q24.1-rs2277598 as novel risk loci for pancreatic ductal adenocarcinoma.

Coding sequence variants comprise a small fraction of the germline genetic variability of the human genome. However, they often cause deleterious change in protein function and are therefore associated with pathogenic phenotypes. To identify novel pancreatic ductal adenocarcinoma (PDAC) risk loci, we carried out a complete scan of all common missense and synonymous SNPs and analysed them in a case-control study comprising four different populations, for a total of 14 538 PDAC cases and 190 657 controls.

Infection in a Duodenal Duplication Cyst as a Potential Cause of Recurrent Acute Pancreatitis.

is a known etiological factor of a common infectious diarrhea. In rare cases, this parasite was found to be involved in the development of pancreatic and biliary tract diseases, both inflammatory and neoplastic. We present a case of a 64-year-old man known for a duodenal duplication cyst since 2013, with episodes of recurrent acute pancreatitis since 2017.

The PANcreatic Disease ReseArch (PANDoRA) consortium: Ten years' experience of association studies to understand the genetic architecture of pancreatic cancer.

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.

Polymorphic variants involved in methylation regulation: a strategy to discover risk loci for pancreatic ductal adenocarcinoma.

Introduction: Only a small number of risk factors for pancreatic ductal adenocarcinoma (PDAC) has been established. Several studies identified a role of epigenetics and of deregulation of DNA methylation. DNA methylation is variable across a lifetime and in different tissues; nevertheless, its levels can be regulated by genetic variants like methylation quantitative trait loci (mQTLs), which can be used as a surrogate.

The role of biliary events in treatment and survival of patients with advanced pancreatic ductal adenocarcinoma.

Background: Systemic chemotherapy (CT) is the treatment of choice for advanced pancreatic ductal adenocarcinoma (PDAC). Biliary obstruction is common in this setting and may interfere with CT administration due to jaundice or cholangitis related to biliary stent malfunction.

Aims: To evaluate the impact of biliary events on CT administration and survival in patients with stage III-IV PDAC.

EUS-Guided Choledocho-duodenostomy Using Lumen Apposing Stent Versus ERCP With Covered Metallic Stents in Patients With Unresectable Malignant Distal Biliary Obstruction: A Multicenter Randomized Controlled Trial (DRA-MBO Trial).

Background & Aims: Several studies have compared primary endoscopic ultrasound (EUS)-guided biliary drainage to endoscopic retrograde cholangiopancreatography (ERCP) with insertion of metal stents in unresectable malignant distal biliary obstruction (MDBO) and the results were conflicting. The aim of the current study was to compare the outcomes of the procedures in a large-scale study.

Methods: This was a multicenter international randomized controlled study.

Genetic and non-genetic risk factors for early-onset pancreatic cancer.

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.