659 Background: Early detection of pancreatic ductal adenocarcinoma (PDAC) has a significant impact on pancreatic cancer outcomes. Despite this, 4 in 5 patients are diagnosed at later disease stage where surgery is no longer an option. There is a need for more accurate and less burdensome testing methodology. We previously conducted two independent clinical validation studies (CLARITI and VERIFI) where PancreaSure, a serum-based early detection test for PDAC, showed high accuracy in differentiating early-stage disease versus high-risk control patients. To further understand the performance of the test across a varied patient population, we set out to determine test performance in Stage I-IV PDAC and in healthy controls. Methods: PancreaSure, a biomarker signature comprising a mathematical summation of ICAM-1, THSB1, CTSD, TIMP1, and CA19-9 values with a predefined cutoff to differentiate Stage I and Stage II PDAC from controls at high-risk due to genetic/familial background, was assessed for sensitivity and specificity in detecting Stage III and IV PDAC and in normal, healthy controls. Pooled analysis was conducted to determine weighted performance across all stages of PDAC and in high-risk and healthy controls. Results: The study comprised 317 Stage I-II (early stage) and 152 Stage III-IV (late stage) PDAC cases, 1134 high-risk controls, and 295 healthy controls that were collected from US and European sites. PancreaSure overall weighted sensitivity was 79.8% (73.3-86.4% 95% CI). Sensitivity was 77.6% (73.0-82.2%, 95% CI) in early-stage PDAC and 88.2% (81.8-93.0%, 95% CI) in late-stage PDAC. Overall weighted specificity was 90.8% (87.8-93.8% 95% CI). Specificity was 92.2% (90.6-93.7%, 95% CI) in high-risk controls and 97.7% (95.3-99.1%, 95% CI) in healthy controls. Conclusions: Across a robust clinical experience of almost 1900 patients, PancreaSure showed high accuracy across Stage I-IV PDAC, with improved performance in late-stage disease and in healthy controls. These results support the robustness of the test’s performance and can serve as a tool for both early-stage and late-stage PDAC detection in patients at high and normal risk of pancreatic cancer.

INTRODUCTION:To determine the appropriate postpolypectomy colonoscopy surveillance interval, endoscopists synthesize information from colonoscopy and pathology report impressions and subsequently apply guideline-recommended interval algorithms, such as those developed by the United States Multi-Society Task Force. Given the complexity of these guidelines, this manual process is error-prone, necessitating automated tools, including large language models (LLMs), to improve guideline adherence. The primary aim of this study was to identify the LLM performance in determining the guideline-concordant postpolypectomy surveillance interval on a cohort of 1,000 real-world colonoscopy and pathology report impressions. METHODS:The data of patients who underwent a screening or surveillance colonoscopy in 2023-2024 at 2 academic health centers were included. Using a custom prompt outlining the US Multi-Society Task Force postpolypectomy surveillance algorithm, the LLM (GPT-4o) was asked to determine the appropriate surveillance interval for all 1,000 examples in the data set. This experiment, using the same model, prompt, and data set, was repeated 10 times; all experiments were conducted between January 27, 2025, and February 3, 2025. RESULTS:Across 10 experiments, the average accuracy was 94.6%. There was no significant difference in accuracy based on the institution from which the data originated or the presence of synchronous upper gastrointestinal endoscopy data within the pathology report impression. Examples with 1-3 colon polyps had an average accuracy of 95.8% whereas examples with 4 or more colon polyps had an average accuracy of 88.2%, combined P value < 0.001. DISCUSSION:LLMs with a custom prompt achieve consistently high accuracy in determining the guideline-based surveillance colonoscopy interval.

11139 Background: Timely detection of pathogenic variants enables personalized treatment and improved outcomes in prostate cancer (PC). In 2020, NCCN guidelines recommended genomic testing for mPC, but by 2022, only 30.8% of mPC patients in Florida had undergone appropriate testing. In our current study, we evaluate the impact of system-wide quality improvements at SCCC on genomic testing rates for mPC patients. Methods: In alignment with NCCN guidelines, several initiatives were launched in 2023 to enhance adherence to genomic testing practices. In May 2024, SCCC partnered with Florida Society of Clinical Oncology (FLASCO) and Pfizer on a state-wide initiative to address barriers to germline testing. A survey was conducted to assess the genomic testing process and identify gaps in adherence. System improvement projects were initiated, accompanied by efforts to raise awareness. A retrospective analysis utilizing EPIC Electronic medical record (EMR) data evaluated genomic testing rates among patients with newly identified mPC at SCCC from 2022 to 2024, stratified by ethnicity. Results: In 2022, baseline genomic testing rates for mPC at SCCC were 57%. Starting in 2023, high-risk cancer screening programs and EMR-focused initiatives, including the Genomics Module and Invitae integration, centralized molecular results and established registry to track alterations. In 2024, the survey revealed that 50% of physicians received unstructured genomic testing results via EMR, while 83.3% faced challenges accessing results for decision-making. Drawing from the successful breast cancer screening program, multidisciplinary teams were formed to address gaps and enhance testing adherence, focusing on awareness and enhancing EMR integration, reporting, and health prompts. That year, genomic results integration into the data portal also began. Using Slicer Dicer and Epic reporting, we evaluated testing rates, which improved to 68.6% in 2023 and 74% in 2024, with Hispanic patients achieving 76.5% and 80%, respectively. Conclusions: Institutional initiatives at SCCC, including expanding the Genetics program and enhancements to EMR functionality, have successfully increased genomic testing rates for mPC patients across all ethnicities. Building on this progress, approved steps for 2025 include expanding the integration of molecular testing with additional testing vendors, creating a dedicated Molecular tab with discrete fields in the EMR, and expanding education and training programs to further streamline genomic testing practices. Year Testing Rate Hispanic Initiatives 2022 57% 50% – 2023 68.6% 76.5% Jan – High Risk Screening ClinicFeb – Genetic Predisposition Syndrome ClinicOct – Invite integrationOct – Epic Genomics Module 2024 74% 80% May – mPC Testing Workflow assessedSep – SCCC data portal- molecular testing results integrationOct – Multidisciplinary team to identify gaps and prioritize projects

BACKGROUND:Crohn's disease (CD) is characterized by an inflammatory response to gut microbiota. Macrophages and dendritic cells play an active role in CD inflammation. Specific microbiota have been implicated in the pathogenesis of ileal CD. We investigated the phagocyte-associated microbiome using an unbiased sequencing approach to identify potential pathobionts and elucidate the host response to these microbes. METHODS:We collected ileal and colonic mucosal biopsies from CD patients and controls without inflammatory bowel disease (IBD), isolated lamina propria phagocytes (CD11b+ cells), and performed deep RNA sequencing (n = 37). Reads were mapped to the human genome for host gene expression analysis and a prokaryotic database for microbiome taxonomic and metatranscriptomic profiling. Results were confirmed in a second IBD cohort (n = 17). Lysed lamina propria cells were plated for bacterial culturing; isolated colonies underwent whole genome sequencing (n = 11). RESULTS:Crohn's disease ileal phagocytes contained higher relative abundances of Escherichia coli, Ruminococcus gnavus, and Enterocloster spp. than those from controls. CD phagocyte-associated microbes had increased expression of lipopolysaccharide (LPS) biosynthesis pathways. Phagocytes with a higher pathobiont burden showed increased expression of pro-inflammatory and antimicrobial genes, including PI3 (antimicrobial peptide) and BPIFB1 (LPS-binding molecule). E. coli isolated from the CD lamina propria had more flagellar motility and antibiotic resistance genes than control-derived strains. CONCLUSIONS:Lamina propria resident phagocytes harbor bacterial strains that may act as pathobionts in CD. Our findings shed light on the role of pathobionts and the immune response in CD pathogenesis and suggest new targets for therapies.

PURPOSE:Pancreatic cancer (PC) surveillance is increasingly recommended for high-risk individuals, but there are remaining areas of uncertainty that are not consistently addressed by guidelines contributing to heterogeneity in clinical practice. Herein, we compare PC surveillance practices across sites in the international Pancreatic Cancer Early Detection (PRECEDE) Consortium to understand the application of eligibility criteria and testing strategies among experienced PC surveillance centers. METHODS:This analysis represents a cross-sectional survey administered in 2024 to PRECEDE institutions. The site principal investigator (or designee) completed the survey reflecting PC surveillance practices of their site, with one response per institution. Survey questions were related to surveillance eligibility for carriers of BRCA1/2, ATM, PALB2, and Lynch syndrome along with imaging approaches. RESULTS:Of the 57 PRECEDE sites, 54 (95%) completed the survey. For high-risk gene carriers, there was heterogeneity among sites with respect to whether family history of PC was used when assessing eligibility for surveillance. In the absence of family history, 44.4% and 35.2% of sites would offer PC surveillance to BRCA2 and BRCA1 carriers, respectively, whereas 31.5% and 13% would offer surveillance to PALB2/ATM and Lynch syndrome carriers, respectively. There was general consensus that surveillance should start at age 50 for men and women across all included genes. Magnetic resonance imaging with magnetic resonance cholangiopancreatography was used by 64.8% of sites as index imaging. The majority recommended an alternative modality if index imaging was unremarkable, and recommended annual surveillance imaging. CONCLUSION:This is the largest assessment of global PC surveillance practices to date, showing variability in practice patterns. Additional investigation is needed to refine risk stratification for gene carriers without a family history of PC and address optimal imaging strategies.

Pancreatic cancer is the third highest cause of cancer mortality in the United States. Detecting PDAC at an earlier stage with the tumor confined to the pancreas and lymph node negative improves 5-year rates from 3% for late-stage diagnosis to 44%. There is no FDA approved early detection blood test for PDAC. IMMNOV-2, a blood-based protein biomarker model comprising ICAM1, TIMP1, CTSD, THBS1 and CA19-9 was previously shown to differentiate early-stage PDAC from high-risk controls with high sensitivity and specificity. The current study aimed to validate the performance of IMMNOV-2 in detecting early-stage pancreatic cancer in a large clinical population independent from which the model was developed. This was a multi-institutional blinded study assessing the performance of IMMNOV-2 in patient serum samples to differentiate Stage I and Stage II PDAC cases from non-PDAC controls at high-risk due to familial, genetic, or clinical factors. The model’s performance in the whole patient population was also compared to CA19-9 performance alone. IMMNOV-2 comprises four quantitative ELISAs that measure the concentration of the protein biomarkers in human serum. CA19-9 is measured using a Roche COBAS. A fixed mathematical algorithm is employed to integrate the values of the five biomarkers to calculate a positive or negative call based on a predefined cutoff. 202 Stage I and II PDACs and 864 high-risk controls were enrolled. Assays were performed in a blinded manner. IMMNOV-2 distinguished early-stage PDAC from high-risk controls with 78.2% (95% CI, 71.9-83.7) sensitivity at 93.5% (95% CI, 91.7-95.1) specificity. In contrast, CA19-9 alone differentiated early-stage PDAC from controls with 64% (95% CI, 57.3-71) sensitivity (p<0.001 vs IMMNOV-2) at 94.7% (95% CI, 93-96.1) specificity. Performance between Stage I and Stage II PDAC cases were similar. A pre-planned analysis revealed a decrease of IMMNOV-2 performance with increasing age of samples. In samples collected <5 years before the study (89 cases, 751 high-risk controls), sensitivity and specificity of the test was 82.0% (95% CI, 74-90) and 94.9% (95% CI, 93.1-96.4), respectively, which was significantly better than CA19-9 alone (p<0.001) and performance in samples collected >5 yrs before the study (sensitivity 75.2% (95% CI, 67.3-83.2), specificity 84.0% (95% CI, 77.3-90.8), p<0.001). IMMNOV-2 differentiated Stage I and Stage II PDAC from high-risk controls with high accuracy in this large clinical validation study. Model performance was significantly better than CA19-9 alone. Testing in recently collected samples would be consistent with clinical use of the test and results in better performance for detecting early-stage PDAC. These promising data warrant further validation in a next-level study using prospective randomized open blinded endpoint (PROBE) design principles. Bryson Katona, Norma Alonzo Palma, Aimee Lucas, Rosalie Sears, Salvatore Paiella, George Zogopoulos, Eli M. Grindedal, Raymond Wadlow, Erkut Borazanci, Daniel A. Sussman, Ora Gordon, Natasha Kureshi, Lisa Ford, Thomas King, Randall Brand, Diane Simeone. Clinical validation of a novel blood-based protein multi-analyte test for early detection of pancreatic ductal adenocarcinoma (PDAC) in a large, independent high-risk patient population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT088.

Background Gastrointestinal (GI) luminal cancers can be detected at early stages by endoscopic procedures. Place -based factors, such as social deprivation and distance to specialist care, are under-investigated with regard to the stage of diagnosis. Methods This was a retrospective cohort study among persons >= 18 years of age in the Florida Cancer Data System, a population -based cancer incidence registry. We included persons diagnosed with esophageal cancer, gastric canceror colorectal cancer, with at least 1 measure of geographic location during the period January 1, 1981, to December 31, 2016. Multivariate multinomial logistic regression was used to identify factors associated with the stage of diagnosis, including social deprivation and proximity to GI care. Results Among 379,054 persons, the median age was 71 years, and 54% were male. Distant stage disease was significantly less likely than local stage in those of non-Hispanic/Latino ethnicity (odds ratio [OR] 0.92, 95% confidence interval [CI] 0.89-0.94, P<0.001). Distant disease was more likely in African Americans (OR 1.30, 95%CI 1.26-1.34) and Asians (OR 1.41, 95%CI 1.27-1.56, P<0.001), with each 5 -min increase in travel time to specialists, (OR 1.02, 95%CI 1.01-1.02, P<0.001), and with each 10 -point increase in Social Deprivation Index (OR 1.01, 95%CI 1.01-1.02, P<0.001). Conclusions A greater distance from care and living in areas with increased deprivation are associated with an advanced stage of diagnosis and should be recipients of policy -driven efforts to improve access to care. That the strongest risk factors include minority race and ethnicity underlines the complexity of healthcare disparities.

BACKGROUND:Pancreatic adenocarcinoma (PC) is a highly lethal malignancy with a survival rate of only 12%. Surveillance is recommended for high-risk individuals (HRIs), but it is not widely adopted. To address this unmet clinical need and drive early diagnosis research, we established the Pancreatic Cancer Early Detection (PRECEDE) Consortium. METHODS:PRECEDE is a multi-institutional international collaboration that has undertaken an observational prospective cohort study. Individuals (aged 18-90 years) are enrolled into 1 of 7 cohorts based on family history and pathogenic germline variant (PGV) status. From April 1, 2020, to November 21, 2022, a total of 3,402 participants were enrolled in 1 of 7 study cohorts, with 1,759 (51.7%) meeting criteria for the highest-risk cohort (Cohort 1). Cohort 1 HRIs underwent germline testing and pancreas imaging by MRI/MR-cholangiopancreatography or endoscopic ultrasound. RESULTS:A total of 1,400 participants in Cohort 1 (79.6%) had completed baseline imaging and were subclassified into 3 groups based on familial PC (FPC; n=670), a PGV and FPC (PGV+/FPC+; n=115), and a PGV with a pedigree that does not meet FPC criteria (PGV+/FPC-; n=615). One HRI was diagnosed with stage IIB PC on study entry, and 35.1% of HRIs harbored pancreatic cysts. Increasing age (odds ratio, 1.05; P<.001) and FPC group assignment (odds ratio, 1.57; P<.001; relative to PGV+/FPC-) were independent predictors of harboring a pancreatic cyst. CONCLUSIONS:PRECEDE provides infrastructure support to increase access to clinical surveillance for HRIs worldwide, while aiming to drive early PC detection advancements through longitudinal standardized clinical data, imaging, and biospecimen captures. Increased cyst prevalence in HRIs with FPC suggests that FPC may infer distinct biological processes. To enable the development of PC surveillance approaches better tailored to risk category, we recommend adoption of subclassification of HRIs into FPC, PGV+/FPC+, and PGV+/FPC- risk groups by surveillance protocols.

INTRODUCTION:Recent studies have identified a critical role of stromal-immune cell interactions in immunity and immune tolerance. Transcriptomic profiling has implicated stromal cells in immune-mediated disorders including the 2 common forms of inflammatory bowel disease (IBD), Crohn's disease (CD), and ulcerative colitis (UC). Stromal-immune interactions may edify inflammatory state and the development of IBD-related complications such as fibrosis, yet the lack of protein markers has hampered studying stromal-immune perturbation. METHODS:In this study, we designed a 40-color spectral flow cytometry assay to characterize hematopoietic and nonhematopoietic cells in intestinal biopsies and matched blood samples from patients with CD or UC. RESULTS:We identified circulating stromal-like cells that are significantly more abundant in IBD blood samples than in healthy controls. Those cells expressed podoplanin (PDPN), a commonly used marker for fibroblasts, and they were associated with activated and memory T and B cells and altered natural killer cell, monocyte, and macrophage populations. PDPN + cells in the blood correlated with PDPN + cells in the colon. Principal component analysis distinctly separated healthy blood samples from IBD blood samples, with stromal-like cells and B-cell subtypes dominating the IBD signature; Pearson correlation detected an association between PDPN + stromal-like cells and B-cell populations in IBD blood and gut biopsies. DISCUSSION:These observations suggest that PDPN + cells in the blood may serve as a biomarker of IBD. Understanding the relationship between stromal cells and immune cells in the intestine and the blood may provide a window into disease pathogenesis and insight into therapeutic targets for IBD.

In 2021, there were about 17,000 victims of human trafficking in the United States. We present a case of a 28-year-old sex trafficking victim who was forced to swallow 2 global positioning system trackers by her perpetrator. The gastroenterology team performed an upper endoscopy and retrieved 2 global positioning system devices from her antrum. Most of these victims do not disclose any history of abuse because of fear of their perpetrators. Further training and research can help to allow for recognition of these victims and potentially help them.

Background and Aims Corneal abrasion (CA) is a rare endoscopic adverse event. We aimed to document the CA rate before and after implementing universal surgical mask taping to nose bridge and bilateral eye taping pre-endoscopy during the COVID-19 era. Methods All patients undergoing endoscopy were screened for CA. Adverse event rates of CA(AER-CA) were compared to 14 months pre-COVID-19 (BASELINE,1/1/2019-2/29/2020), during COVID-19 pre-QI intervention (COVID PRE-QI,3/1/2020-8/31/2020), and during/after COVID-19 post-QI intervention (POST-QI,9/1/2020-4/3/2023). Fisher’s Exact test compared AER-CA. Results 47,309 total endoscopic procedures were performed with sedation during the COVID PRE-QI and POST-QI periods. BASELINE AER-CA was 0.03%(3/10,715). AER-CA of COVID PRE-QI was 0.09%(4/3,243). The POST-QI AER-CA was 0(0/44,066 procedures). The POST-QI AER-CA was significantly lower compared to BASELINE(p<0.01), COVID PRE-QI(p<0.01), and overall PRE-QI(p<0.01). Discussion A QI intervention with taping the surgical mask to nose bridge and taping eyes closed is an efficacious method of preventing CA in patients undergoing endoscopy and should be considered for adoption.