Genetic testing for pancreatic cancer screening: ready for prime time?

Purpose Of Review: Pancreatic ductal adenocarcinoma (PDAC) has a dismal 13% 5-year survival rate, necessitating early detection and personalized treatment. This review evaluates whether germline genetic testing, integrated with clinical decision support (CDS) tools, is ready for widespread use in PDAC screening. We focus on its potential to identify high-risk individuals (HRIs) beyond those with strong family histories to complex risk and biomarkers, stratifying patients into low-risk and high-risk virtual populations for targeted surveillance.

Machine Learning-Guided Fluid Resuscitation for Acute Pancreatitis Improves Outcomes.

Introduction: Ariel Dynamic Acute Pancreatitis Tracker (ADAPT) is an artificial intelligence tool using mathematical algorithms to predict severity and manage fluid resuscitation needs based on the physiologic parameters of individual patients. Our aim was to assess whether adherence to ADAPT fluid recommendations vs standard management impacted clinical outcomes in a large prospective cohort.

Methods: We analyzed patients consecutively admitted to the Los Angeles General Medical Center between June 2015 and November 2022 whose course was richly characterized by capturing more than 100 clinical variables.

Neutrophil-to-Lymphocyte Ratio Differentiates Infections from Sterile Inflammation in First Week of Acute Pancreatitis.

Background: Differentiating infections from sterile inflammation is crucial in early AP management.

Aim: This study aimed to assess the capability of Neutrophil-to-Lymphocyte Ratio (NLR) and procalcitonin to differentiate between sterile inflammation and infections in the first week of AP and to analyze the source, microbiological profile, and impact of infections in AP.

Methods: Consecutive patients presenting within 5 days of symptom onset were included.

Genetics of constant and severe pain in the NAPS2 cohort of recurrent acute and chronic pancreatitis patients.

Recurrent acute and chronic pancreatitis (RAP, CP) are complex, progressive inflammatory diseases with variable pain experiences impacting patient function and quality of life. The genetic variants and pain pathways in patients contributing to most severe pain experiences are unknown. We used previously genotyped individuals with RAP/CP from the North American Pancreatitis Study II (NAPS2) of European Ancestry for nested genome-wide associated study (GWAS) for pain-severity, chronicity, or both.

Heterogeneity in Pancreatitis: Recognizing Heterogeneity and Its Role in the Management of Pancreatitis Summary of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop.

Both the clinical management and study of recurrent acute pancreatitis and chronic pancreatitis are complicated by significant heterogeneity in the etiology, mechanisms, symptoms, and complications of pancreatitis. The National Institutes of Diabetes and Digestive and Kidney Disease recently convened a workshop to address current knowledge and knowledge gaps in the field. Preclinical models that better replicate human disease are important for development of new therapies.

Cytokine signatures in post-endoscopic retrograde cholangiopancreatography pancreatitis: a pilot study.

Background: Following endoscopic retrograde cholangiopancreatography (ERCP), post-ERCP pancreatitis (PEP) is the most common complication. The host's innate immune response to periprocedural pancreatic injury is the hallmark of its pathogenesis. Investigating cytokine signatures associated with PEP and its risk factors can guide understanding of PEP immunopathogenesis.

Interventions for Pancreatitis-New Approaches, Knowledge Gaps, and Research Opportunities: Summary of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop.

There exists no cure for acute, recurrent acute or chronic pancreatitis and treatments to date have been focused on managing symptoms. A recent workshop held by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) focused on interventions that might disrupt or perhaps even reverse the natural course of this heterogenous disease, aiming to identify knowledge gaps and research opportunities that might inform future funding initiatives for NIDDK. The breadth and variety of identified active or planned clinical trials traverses the spectrum of the disease and was conceptually grouped for the workshop into behavioral, nutritional, pharmacologic and biologic, and mechanical interventions.

The burden of recurrence acute pancreatitis and annual event rates are underestimated because of high rates of home self-management.

Background/objectives: The event-rate of recurrent acute pancreatitis (RAP) in patient populations is critical for powering research studies. We hypothesize that some patients manage RAP attacks at home, reducing event rate estimations based on counting emergency department (ED) visits and hospitalizations only. The aim of this study was to determine the rates of home self-management of recurrent acute pancreatitis compared to ED visits and hospitalizations.

Relationship of circulating levels of long-chain fatty acids to persistent organ failure in acute pancreatitis.

During acute pancreatitis (AP), free fatty acids (FFAs) are liberated from circulating triglycerides (TG) and injured adipocytes by pancreatic lipase. Circulating FFAs have been suspected as a source of systemic lipotoxicity in AP. However, assessment of FFAs is difficult and time-consuming, and little is known about relative levels of FFAs between patients with different severities of AP and controls.

Evinacumab in severe hypertriglyceridemia with or without lipoprotein lipase pathway mutations: a phase 2 randomized trial.

Severe hypertriglyceridemia (sHTG) is an established risk factor for acute pancreatitis. Current therapeutic approaches for sHTG are often insufficient to reduce triglycerides and prevent acute pancreatitis. This phase 2 trial ( NCT03452228 ) evaluated evinacumab (angiopoietin-like 3 inhibitor) in three cohorts of patients with sHTG: cohort 1, familial chylomicronemia syndrome with bi-allelic loss-of-function lipoprotein lipase (LPL) pathway mutations (n = 17); cohort 2, multifactorial chylomicronemia syndrome with heterozygous loss-of-function LPL pathway mutations (n = 15); and cohort 3, multifactorial chylomicronemia syndrome without LPL pathway mutations (n = 19).

Acute pancreatitis precedes chronic pancreatitis in the majority of patients: Results from the NAPS2 consortium.

Introduction: The mechanistic definition of chronic pancreatitis (CP) identifies acute pancreatitis (AP) as a precursor stage. We hypothesized that clinical AP frequently precedes the diagnosis of CP and is associated with patient- and disease-related factors. We describe the prevalence, temporal relationship and associations of AP in a well-defined North American cohort.

Clinical Trials in Pancreatitis: Opportunities and Challenges in the Design and Conduct of Patient-Focused Clinical Trials in Recurrent Acute and Chronic Pancreatitis: Summary of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop.

Recurrent acute pancreatitis and chronic pancreatitis represent high morbidity diseases, which are frequently associated with chronic abdominal pain, pancreatic insufficiencies, and reduced quality of life. Currently, there are no therapies to reverse or delay disease progression, and clinical trials are needed to investigate potential interventions that would address this important gap. This conference report provides details regarding information shared during a National Institute of Diabetes and Digestive and Kidney Diseases-sponsored workshop on Clinical Trials in Pancreatitis that sought to clearly delineate the current gaps and opportunities related to the design and conduct of patient-focused trials in recurrent acute pancreatitis and chronic pancreatitis.

Development of a Clinical Prediction Model for Diabetes in Chronic Pancreatitis: The PREDICT3c Study.

Objective: Diabetes that arises from chronic pancreatitis (CP) is associated with increased morbidity and mortality. Methods to predict which patients with CP are at greatest risk for diabetes are urgently needed. We aimed to examine independent risk factors for diabetes in a large cohort of patients with CP.

AGA-PancreasFest Joint Symposium on Exocrine Pancreatic Insufficiency.

Exocrine pancreatic insufficiency (EPI) is a clinically defined syndrome based on the physician's assessment of a patient's maldigestion. However, current clinical definitions are inadequate in determining (1) the threshold of reduced pancreatic digestive enzyme secretion that determines "pancreatic insufficiency" in an individual patient; (2) the role of pancreatic function tests; (3) effects of differing metabolic needs, nutrition intake, and intestinal function/adaptation (4) when pancreatic enzyme replacement therapy is needed; and (5) how to monitor and titrate multiple therapies. Experts and key opinion leaders were invited to to discuss and help clarify mechanistic issues critical to defining EPI and to address misconceptions and barriers limiting advancements in patient care.