Multi-omic markers of Intraductal Papillary Mucinous Neoplasms progression into pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is the most lethal and common form of pancreatic cancer, it has no specific symptoms, and most of the patients are diagnosed when the disease is already at an advanced stage. Chemotherapy typically has only a modest effect, making surgery the most effective treatment option. However, only a small percentage of patients are amenable to surgery.

Hepatic Steatosis and Fibrosis, Cardiorespiratory Fitness, and Metabolic Mediators in the Community.

Background And Aims: Individuals with steatotic liver disease (SLD) are at high cardiovascular disease (CVD) risk, but approaches to characterise and mitigate this risk are limited. By investigating relations, and shared metabolic pathways, of hepatic steatosis/fibrosis and cardiorespiratory fitness (CRF), we sought to identify new avenues for CVD risk reduction in SLD.

Methods: In Framingham Heart Study (FHS) participants (N = 2722, age 54 ± 9 years, 53% women), vibration-controlled transient elastography (VCTE) was performed between 2016-2019 to assess hepatic steatosis (continuous attenuation parameter [CAP]) and fibrosis (liver fibrosis measure [LSM]).

Challenges in developing response evaluation criteria for peptide receptor radionuclide therapy: A consensus report from the European Neuroendocrine Tumor Society Advisory Board Meeting 2022 and the ENETS Theranostics Task Force.

Assessing the response to systemic therapy in neuroendocrine tumors (NET) is challenging since morphological imaging response is often delayed and not necessarily reflective of clinical benefit. Peptide receptor radionuclide therapy (PRRT) has a complex mechanism of action, further complicating response assessment. In response to these challenges, the European Neuroendocrine Tumor Society (ENETS) Theranostics Task Force conducted a statement-based survey among experts to identify the current landscape and unmet needs in PRRT response assessment.

A genome-wide association study identifies eight loci associated with intraductal papillary mucinous neoplasm progression toward malignancy.

Background: Intraductal papillary mucinous neoplasms (IPMNs) are precursors to pancreatic cancer, but not all IPMNs progress to cancer. The objective of this study was to identify the germline genetic variants associated with IPMN clinical progression by conducting the first genome-wide association study (GWAS) and computing a polygenic hazard score (PHS) in 338 patients with IPMN.

Methods: The study population was divided into two subsets, and a Cox analysis adjusted for sex, age, cyst size at diagnosis, and the top 10 principal components was performed.

Pancreatic Neuroendocrine Neoplasms: Classification and Novel Role of Endoscopic Ultrasound in Diagnosis and Treatment Personalization.

The incidence and prevalence of pancreatic neuroendocrine neoplasms are steadily increasing. These tumors are highly heterogeneous, with treatment options ranging from observation to surgery, and various medical therapies. The choice of treatment is influenced by factors such as tumor stage, grade (proliferative activity), and the presence of hormone-related syndromes.

Clinical and Financial Validation of the International Study Group for Pancreatic Surgery (ISGPS) Definition of Post-Pancreatectomy Acute Pancreatitis (PPAP): International Multicenter Prospective Study.

Objective: To validate the ISGPS definition and grading system of PPAP after pancreatoduodenectomy (PD).

Summary Background Data: In 2022, the International Study Group for Pancreatic Surgery (ISGPS) defined post-pancreatectomy acute pancreatitis (PPAP) and recommended a prospective validation of its diagnostic criteria and grading system.

Methods: This was a prospective, international, multicenter study including patients undergoing PD at 17 referral pancreatic centers across Europe, Asia, Oceania, and the United States.

Normal saline versus lactated Ringer's solution for acute pancreatitis resuscitation, an open-label multicenter randomized controlled trial: the WATERLAND trial study protocol.

Background: Some evidence suggests that fluid resuscitation with lactated Ringer's solution (LR) may have an anti-inflammatory effect on acute pancreatitis (AP) when compared to normal saline (NS) and may be associated with a decrease in severity, but existing single-center randomized controlled trials showed conflicting results. The WATERLAND trial aims to investigate the efficacy and safety of fluid resuscitation using LR compared to NS in patients with AP.

Methods: The WATERLAND trial is an international multicenter, open-label, parallel-group, randomized, controlled, superiority trial.

Principle of sample size calculation in gastroenterology research: a practical guide for clinicians.

Introduction: A proper sample size calculation enables to conduct adequately powered randomized controlled trials (RCTs) and to provide a valid assessment of a specific clinical question.

Areas Covered: In the current manuscript, we tried to provide the reader with an easy guide on the principles of sample size calculation in RCTs, tailored specifically to the context of gastroenterology and hepatology. The basics of sample size calculation were commented with a description of some of the main methods, including the calculation of the non-inferiority margin for non-inferiority RCTs and the calculation of the minimum clinically important difference (MCID).

Cardiomyocyte-derived circulating extracellular vesicles allow a non-invasive liquid biopsy of myocardium in health and disease.

The ability to track disease without tissue biopsy in patients is a major goal in biology and medicine. Here, we identify and characterize cardiomyocyte-derived extracellular vesicles in circulation (EVs; "cardiovesicles") through comprehensive studies of induced pluripotent stem cell-derived cardiomyocytes, genetic mouse models, and state-of-the-art mass spectrometry and low-input transcriptomics. These studies identified two markers (, ) enriched on cardiovesicles for biotinylated antibody-based immunocapture.

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.

Biliary drainage in patients with malignant distal biliary obstruction: results of an Italian consensus conference.

Background: Malignant Distal Biliary Obstruction (MBDO) is a common event occurring along the natural history of both pancreatic cancer and cholangiocarcinoma. Epidemiological and biological features make MBDO one of the key elements of the clinical management of patients suffering for of pancreatic cancer or cholangiocarcinoma. The development of dedicated biliary lumen-apposing metal stents (LAMS) is changing the clinical work up of patients with MBDO.

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.

A pilot study of chlorambucil in pre-treated metastatic pancreatic adenocarcinoma patients bearing germline BRCA or other DNA damage repair system variants.

Backgorund: Pancreatic adenocarcinoma remains a malignancy with a grim prognosis and scarce personalized treatment options. Pathogenic variants of DNA damage repair (DDR) genes are emerging as molecular targets, as they confer a higher sensitivity to DNA-damaging agents. This study aimed at assessing the activity of chlorambucil as salvage therapy in metastatic pancreatic cancer patients bearing a germline pathogenetic variant or variant of uncertain significance on a DDR-related gene.

Unveiling hidden outcomes in malignant gastric outlet obstruction research - insights from a "Pancreas 2000" review.

Malignant gastric outlet obstruction (mGOO) is a major condition affecting patients with periampullary tumors, including pancreatic cancer. The current treatment options include surgical gastroenterostomy, endoscopic stenting and more recently EUS-guided gastroenterostomy. Most studies comparing the outcomes of the three procedures focus on technical success, clinical success and safety.

Global trends in opioid use for pain management in acute pancreatitis: A multicentre prospective observational study.

Background: Since there is no current international consensus on the optimal approach for pain management in acute pancreatitis (AP), analgesic practices may vary across different healthcare settings.

Objective: This study explored global disparities in analgesic use, in particular opioids, during admission and at discharge in hospitalised AP patients.

Methods: This was a post hoc analysis of the prospective PAINAP database, which included all admissions for AP between April and June 2022 with a 1-month follow-up.

The i-EUS consensus on the management of pancreatic fluid collections - Part 1.

Pancreatic fluid collections (PFCs), including pancreatic pseudocysts (PPs) and walled-off pancreatic necrosis (WON), are common complications of pancreatitis and pancreatic surgery. Historically, the treatment of these conditions has relied on surgical and radiological approaches; however, it has later shifted toward an endoscopy-based approach. With the development of dedicated lumen-apposing metal stents (LAMS), interventional Endoscopic Ultrasound (EUS)-guided procedures have become the standard approach for PFC drainage.

Futility of Up-Front Resection for Anatomically Resectable Pancreatic Cancer.

Importance: There are currently no clinically relevant criteria to predict a futile up-front pancreatectomy in patients with anatomically resectable pancreatic ductal adenocarcinoma.

Objectives: To develop a futility risk model using a multi-institutional database and provide unified criteria associated with a futility likelihood below a safety threshold of 20%.

Design, Setting, And Participants: This retrospective study took place from January 2010 through December 2021 at 5 high- or very high-volume centers in Italy.

Complexity and Experience Grading to Guide Patient Selection for Minimally-invasive Pancreatoduodenectomy: An ISGPS Consensus.

Objective: The ISGPS aims to develop a universally accepted complexity and experience grading system to guide the safe implementation of robotic and laparoscopic minimally-invasive pancreatoduodenectomy (MIPD).

Background: Despite the perceived advantages of MIPD, its global adoption has been slow due to the inherent complexity of the procedure and challenges to acquiring surgical experience. Its wider adoption must be undertaken with an emphasis towards appropriate patient selection according to adequate surgeon and center experience.