Early detection of pancreatic cancer: Study design and analytical considerations in biomarker discovery and early phase validation studies.

Objectives: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease that is challenging to detect at an early stage. Biomarkers are needed that can detect PDAC early in the course of disease when interventions lead to the best outcomes. We highlight study design and statistical considerations that inform pancreatic cancer early detection biomarker evaluation.

Sphincterotomy for biliary sphincter of Oddi disorder and idiopathic acute recurrent pancreatitis: the RESPOnD longitudinal cohort.

Objective: Sphincter of Oddi disorders (SOD) are contentious conditions in patients whose abdominal pain, idiopathic acute pancreatitis (iAP) might arise from pressurisation at the sphincter of Oddi. The present study aimed to measure the benefit of sphincterotomy for suspected SOD.

Design: Prospective cohort conducted at 14 US centres with 12 months follow-up.

Technical Factors Associated With the Benefit of Prophylactic Pancreatic Stent Placement During High-Risk Endoscopic Retrograde Cholangiopancreatography: A Secondary Analysis of the SVI Trial Data Set.

Introduction: Prophylactic pancreatic stent placement (PSP) is effective for preventing pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk cases, but the optimal technical approach to this intervention remains uncertain.

Methods: In this secondary analysis of 787 clinical trial patients who underwent successful stent placement, we studied the impact of (i) whether pancreatic wire access was achieved for the sole purpose of PSP or naturally during the conduct of the case, (ii) the amount of effort expended on PSP, (iii) stent length, (iv) stent diameter, and (v) guidewire caliber. We used logistic regression models to examine the adjusted association between each technical factor and post-ERCP pancreatitis (PEP).

Development of American Society for Gastrointestinal Endoscopy standards for training in advanced endoscopy within dedicated advanced endoscopy fellowship programs.

Background And Aims: Training in interventional endoscopy is offered by nonaccredited advanced endoscopy fellowship programs (AEFPs). The number of these programs has increased dramatically with a concurrent increase in the breadth and complexity of interventional endoscopy procedures. Accreditation is governed by competency-based education, yet what constitutes a "high-quality" nonaccredited AEFP has not been defined.

Sphincterotomy for Biliary Sphincter of Oddi Disorder and idiopathic Acute Recurrent Pancreatitis: THE RESPOND LONGITUDINAL COHORT.

Objective: Sphincter of Oddi Disorders (SOD) are contentious conditions in patients whose abdominal pain, idiopathic acute pancreatitis (iAP) might arise from pressurization at the sphincter of Oddi. The present study aimed to measure the benefit of sphincterotomy for suspected SOD.

Design: Prospective cohort conducted at 14 U.

Rise in First-Time ERCP for Benign Indications >1 Year After Cholecystectomy Is Associated With Worse Outcomes.

Background & Aims: Greater availability of less invasive biliary imaging to rule out choledocholithiasis should reduce the need for diagnostic endoscopic retrograde cholangiopancreatography (ERCP) in patients who have a remote history of cholecystectomy. The primary aims were to determine the incidence, characteristics, and outcomes of individuals who undergo first-time ERCP >1 year after cholecystectomy (late-ERCP).

Methods: Data from a commercial insurance claim database (Optum Clinformatics) identified 583,712 adults who underwent cholecystectomy, 4274 of whom underwent late-ERCP, defined as first-time ERCP for nonmalignant indications >1 year after cholecystectomy.

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.

Phosphatidylethanol Detects Occult Heavy Alcohol Use in Patients With Acute and Chronic Pancreatitis.

Given the paucity of interventions to treat pancreatitis, it is imperative to identify and intervene upon modifiable risk factors such as heavy alcohol use. Current trends indicate a concerning increase in alcohol misuse and alcohol-related disease since the onset of the coronavirus disease-2019 pandemic. The incidence of pancreatitis associated with alcohol misuse has increased by approximately 3% annually from 1961 to 2016.

Indomethacin with or without prophylactic pancreatic stent placement to prevent pancreatitis after ERCP: a randomised non-inferiority trial.

Background: The combination of rectally administered indomethacin and placement of a prophylactic pancreatic stent is recommended to prevent pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk patients. Preliminary evidence suggests that the use of indomethacin might eliminate or substantially reduce the need for stent placement, a technically complex, costly, and potentially harmful intervention.

Methods: In this randomised, non-inferiority trial conducted at 20 referral centres in the USA and Canada, patients (aged ≥18 years) at high risk for post-ERCP pancreatitis were randomly assigned (1:1) to receive rectal indomethacin alone or the combination of indomethacin plus a prophylactic pancreatic stent.

A Randomized Controlled Phase 2 Dose-Finding Trial to Evaluate the Efficacy and Safety of Camostat in the Treatment of Painful Chronic Pancreatitis: The TACTIC Study.

Background & Aims: Chronic pancreatitis (CP) causes an abdominal pain syndrome associated with poor quality of life. We conducted a clinical trial to further investigate the efficacy and safety of camostat, an oral serine protease inhibitor that has been used to alleviate pain in CP.

Methods: This was a double-blind randomized controlled trial that enrolled adults with CP with a baseline average daily worst pain score ≥4 on a numeric rating system.

Endotherapy for Pancreas Divisum.

Pancreas divisum (PD) is a common anatomic variant of the pancreatic duct. Causal association between PD and pancreatitis has been debated for many years. Minor papilla sphincterotomy (miES) is offered in clinical practice to patients with idiopathic acute recurrent pancreatitis (iRAP) and PD.

Utilization pattern of prophylactic measures for prevention of post-ERCP pancreatitis: a National Survey Study.

Background And Aims: Post-ERCP pancreatitis (PEP) is the most frequent adverse event of ERCP. Various prophylactic measures are endorsed by the American Society for Gastrointestinal Endoscopy and the European Society of Gastrointestinal Endoscopy to both lower the incidence of PEP and to decrease its severity. The extent to which these interventions are practiced throughout the United States is unclear.

An Evaluation of Critical Factors for the Cost-Effectiveness of Real-Time Computer-Aided Detection: Sensitivity and Threshold Analyses Using a Microsimulation Model.

Background & Aims: The use of computer-aided detection (CAD) increases the adenoma detection rates (ADRs) during colorectal cancer (CRC) screening/surveillance. This study aimed to evaluate the requirements for CAD to be cost-effective and the impact of CAD on adenoma detection by endoscopists with different ADRs.

Methods: We developed a semi-Markov microsimulation model to compare the effectiveness of traditional colonoscopy (mean ADR, 26%) to colonoscopy with CAD (mean ADR, 37%).

Design and execution of sham-controlled endoscopic trials in acute pancreatitis: Lessons learned from the SHARP trial.

Using the ongoing NIDDK-funded multicenter randomized clinical trial, Sphincterotomy for Acute Recurrent Pancreatitis (SHARP) as an example, this article discusses the rationale and key aspects of study design that need to be considered when conducting a clinical trial of endoscopic therapy in acute pancreatitis. SHARP, the first trial using a sham ERCP in the placebo group, is designed to address a decades long controversy in clinical pancreatology, i.e.

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.

The relationship between pre-existing diabetes mellitus and the severity of acute pancreatitis: Report from a large international registry.

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.

Serum biomarkers for chronic pancreatitis pain patterns.

Objectives: Chronic pancreatitis (CP) is associated with debilitating refractory pain. Distinct subtypes of CP pain have been previously characterized based on severity (none, mild-moderate, severe) and temporal (none, intermittent, constant) nature of pain, but no mechanism-based tools are available to guide pain management. This exploratory study was designed to determine if potential pain biomarkers could be detected in patient serum and whether they associate with specific pain patterns.

Pancreas Academy: A Conference-Based Approach for Improving Education in Pancreatic Diseases.

The Collaborative Alliance for Pancreatic Education and Research developed Pancreas Academy as a lecture-based conference with the goal of providing practical guidance in the diagnosis and management of pancreatic diseases for health care providers. Since its inception in 2017, attendance at Pancreas Academy has steadily grown every year, with trainees accounting for the largest proportion of attendees. The proportion of advanced practice providers and pediatric specialists attending the conference, although relatively low, has also risen each year.