Citations

Abstract Background: The Pancreatic Cancer Detection Consortium (PCDC) is an NCI-sponsored initiative to improve detection of early-stage pancreatic ductal adenocarcinoma (PDAC). A key strategy in this initiative is to develop prospective, multi-center, longitudinal biospecimen collections from individuals without PDAC who are at high-risk of PDAC due to family history, germline variants, or the presence of pancreatic cystic lesions. The biospecimen collections, linked to clinically relevant data, will enable Phase 3 biomarker validation studies. Methods: The PCDC currently includes 10 funded Research Units (RUs): City of Hope/TGen, Dana Farber Cancer Institute, Johns Hopkins Medical Institute, Mayo Clinic/University of Pennsylvania, MD Anderson Cancer Center, Oregon Health and Science University, University of Nebraska, University of Pittsburgh Medical Center, University of California (UC) San Diego, UC San Franciso. Non-protected patient health information and biospecimen data is logged into a central Medidata Rave® database managed by a Management and Data Coordination Unit (MDCU) at Mayo Clinic (NCT06271291). Biospecimens collected include blood and pancreatic cyst fluid. Two options for blood collections exist: 1) 20 mL EDTA, 10 mL no additive if samples can be frozen within 4 hours of collection; 2) 10 mL EDTA, 10 mL Streck, 10 mL no additive if samples cannot be frozen within 4 (but less than 12) hours. Cyst fluid (up to 1000 uL), if available as clinical residual, will be obtained at the time of clinically indicated operative resection or endoscopic ultrasound guided aspiration procedures. All samples must be processed per standardized methods outlined in the lab manual and aliquoted into 500 uL (blood) or 100 uL (cyst fluid) units and frozen (-70oC). Long-term biospecimen storage will be set up at NCI Frederick National Laboratory (FNL). Single Institutional Review Board (sIRB) oversight is provided by Mayo Clinic. A collaborative research agreement has been executed to allow sharing of data and biospecimens between and within PCDC RU members, the MDCU, NCI and NCI FNL. Results: The enrollment of patients began February 7, 2025 with additional sites joining as necessary sIRB reliance documents and training is completed. The protocol is approved for up to 30,000 patients, age 18 years and older. 14 have been enrolled from 1 site as of July 10, 2025. Study endpoints include diagnosis of PDAC, death or complete pancreatectomy for non-PDAC reasons. Biospecimens and questionnaires will be collected annually. Summary and Future Plans: The PCDC has designed a Phase 3 biobank following EDRN study design principles. Biospecimens will be stored at NCI FNL. Access to the biobank resource will be overseen by the PCDC Steering Committee. We anticipate this being a rich Phase 3 biospecimen resource for the pancreatic cancer early detection research community. Citation Format: Janet E. Olson, Shounak Majumder, Jennifer J. Brooks, Emily J. Kirsch, Bridget H. Schmidt, Bill R. Bamlet, Erin E. Carlson, Ann L. Oberg. On the development of the Pancreatic Cancer Detection Consortium (PCDC) Prospective Cohorts biobank [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research—Emerging Science Driving Transformative Solutions; Boston, MA; 2025 Sep 28-Oct 1; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_3):Abstract nr B069.

Abstract Objective: The Pancreatic Cancer Detection Consortium (PCDC) performed a blinded EDRN defined phase 2 Biomarker Bakeoff study of eight promising biomarker panels using pancreatic cancer ductal adenocarcinoma (PDAC) case and general population healthy control samples from three institutions. The scientific questions were to determine whether panels could discriminate PDAC cases from controls with Receiver Operating Characteristic Area Under the Curve (AUC) > 0.8, compare panel performance head-to-head via 95% confidence intervals (CI), and determine whether the panel improved upon serum CA19-9 alone. A secondary goal was to perform modeling to discover a new panel consisting of individual biomarkers. Methods: Eligible biomarkers were required to have had a prior EDRN defined phase 2 validation study published and be ready for validation in a sample set from multiple institutions. Three institutions submitted a total of 140 cases and 140 controls frequency matched to cases on age and sex. Four consortium member institutions submitted for validation eight panels consisting of ten plasma, serum and DNA genotyping biomarkers in addition to CA19-9. Locked panel formulas were submitted prior to specimen distribution. The primary metric was AUC with bootstrapped 95% CIs. LASSO penalized regression was used for exploratory panel building. Nested cross validation and internal-external validation were performed, and optimism-corrected performance estimates were computed. Results: The overall sample (N=280) was 51% female, median age of 67 years, and 94% were of non-Hispanic white race and ethnicity. Controls had median BMI 27.3, 56% never smokers, and 12% type II diabetes mellitus (DM2); cases (staged I to IV) had median BMI 26.6, 42% never smokers, and 26% DM2. Overall panel AUC estimates ranged from 89.9 to 96.3 and all were significantly larger than the null hypothesis value of 0.8 (p<0.05). The apparent serum CA19-9 AUC was 91.7 (87.8, 95.6). Two panels were significantly different from serum CA19-9, a panel with FUT2/3 genotype with serum CA19-9 (p=0.002) and a panel containing tissue factor pathway inhibitor (TFPI), tenascin C (TNC), and plasma CA19-9 (p=0.01). In subset analyses by PDAC stage, no panel improved upon the null hypothesis value of 0.8 in stage I (p>0.05), all panels improved upon the null hypothesis value of 0.8 in stage II and III (p<0.05), and only serum CA19-9 did not improve upon the null hypothesis value of 0.8 in stage IV. All biomarkers but two microRNAs were retained in a LASSO model that had optimism corrected AUC=96.4 (95% CI: 94.0, 98.9). Conclusions: All submitted panels performed well overall in this blinded study, with the panel containing FUT2/3 genotype performing the best. Panel discovery improved upon serum CA19-9, though optimism corrected AUC 95% CIs overlap with those of apparent CA19-9 performance. Further work is needed to prioritize promising biomarkers and to improve detection of early stage PDAC. Citation Format: Ann L. Oberg, William R. Bamlet, Grant Izmirlian, Seetharaman Balasenthil, Surinder K. Batra, Masataka Hayashi, Daniel Herman, Michael A. Hollingsworth, Maneesh Jain, Ann M. Killary, Brianna M. Krusen, Suyu Liu, Gopalakrishnan Natarajan, Subrata Sen, Lynette M. Smith, Sudhir Srivastava, Brian M. Wolpin, Kenneth S. Zaret, Michael G. Goggins. Pancreatic Cancer Detection Consortium biomarker bake-off: A consortium Phase 2 blinded biomarker validation and panel discovery study [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research—Emerging Science Driving Transformative Solutions; Boston, MA; 2025 Sep 28-Oct 1; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_3):Abstract nr B070.

Abstract Introduction Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers. While total neoadjuvant therapy (TNT) has improved outcomes, recurrence rates remain high. Major pathologic response after TNT is prognostic of better survival, but is rarely achieved. Current pathologic systems primarily consider residual tumor percentage, nodal status, and perineural invasion but overlook spatial organization within the tumor microenvironment (TME). We aimed to evaluate spatial features of the TME to identify biologically and clinically relevant patterns of TME conformation and configuration after TNT and surgical resection of PDAC. Methods We retrospectively analyzed patients with PDAC treated with TNT followed by surgery at Mayo Clinic (2010-2022) with partial or no response per College of American Pathologists (CAP) criteria. Hematoxylin and eosin-stained whole slide images (WSIs) were processed using PathExplore™ PDAC (v1.0) to quantify spatial TME features. These were correlated with disease-free survival (DFS). Results A total of 203 patients were included: 47.3% female, median age 66.5 years. All received TNT; 73.4% had neoadjuvant chemotherapy followed by chemoradiation. Surgical procedures included pancreaticoduodenectomy (62.1%), distal pancreatectomy (22.2%), and total pancreatectomy (15.8%). CAP-defined response was partial in 82.1% and absent in 17.9%. As expected, pathologic T stage (p=0.001), N stage (p=0.002), lymphovascular invasion (p=0.048), and R2 resection (p=0.007) were significantly associated with DFS. However, CAP response category (p=0.053), residual cancer area (p=0.47), and cancer-to-stroma ratio (p=0.25) were not. We analyzed 297 WSIs from 203 patients. Of 31 spatial features evaluated, 5 were associated with DFS (p<0.20). Recursive partitioning using ln(mean cancer shape index [CSI]) <1.775 and ln(SD of stroma shape index [SSI]) >0.651 identified a high-risk group (n=63) with median DFS of 7.23 months (95% CI: 5.19–9.63), compared to 11.57 months in the low-risk group (95% CI: 9.24–17.92) (HR=1.82; 95% CI: 1.31–2.52; p=0.0003). This remained significant after adjusting for T and N stage (HR=1.75; 95% CI: 1.17–2.63; p=0.007). An alternate prognostic index derived via backwards elimination, calculated using 0.2701(mean stromal area) + 0.3905(edge density), also stratified patients. High-risk patients (n=51) had a significantly shorter (p<0.001) DFS (6.2 months) than those in the low-risk category (20.0 months). This significant difference holds in a multivariable analysis controlling for pathologic stage, N stage, and resection margins (HR=1.94, 95% CI: 1.21-3.10, p=0.006). Discussion Current assessment of residual PDAC after TNT is limited by subjective grading and lack of spatial context. Using Tumor Landscape Analysis, we identified high-risk spatial features of the TME that independently predict recurrence. These findings support a novel spatially-informed framework for risk stratification in resected PDAC with residual disease. Citation Format: Miranda Lin, Luis Cisneros, Merih D. Toruner, Andrea Maraone, Paul Dizona, Qian Shi, Martin E. Fernandez-Zapico, Ryan M. Carr. Spatial features of the tumor microenvironment predict recurrence risk in resected pancreatic ductal adenocarcinoma after total neoadjuvant therapy [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research—Emerging Science Driving Transformative Solutions; Boston, MA; 2025 Sep 28-Oct 1; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_3):Abstract nr A051.

Abstract Background: The neurokinin-1 receptor (NK1R) complex, activated by Substance P (SP), has emerged as a promising target. SP promotes cell growth, whereas its antagonist, Aprepitant (AP), used clinically for chemotherapy-induced nausea, has demonstrated anti-tumor activity. However, further insight on the anti-tumoral mechanisms after antagonistic targeting of the complex are required. Methods: We conducted bioinformatical analysis of public as well as own RNAseq data. Assays to assess cell proliferation and cell viability (MTT, scratch assays, colony formation) as well as apoptosis and autophagy were carried out. Metabolic changes were detected by SeaHorse analysis, ROS, NAD+/NADH, and MitoTracker. Results: Patient-derived organoid cultures showed reduced spheroid formation and altered morphology following AP treatment, while SP enhanced spheroid formation. SP promoted proliferation via Rho-kinase-dependent mechanisms and activated the ERK signaling pathway, with AP slightly reducing pERK levels. Further analyses revealed that AP induces apoptosis signaling without subsequent DNA fragmentation. Annexin V/PI staining indicated apoptosis induction after 24 hours, while subG1 analysis suggested a blockade in the apoptosis cascade. Prolonged AP exposure led to necrosis, which was mitigated by co-treatment with N-acetylcysteine. Western blot analysis confirmed caspase-9 and -3 activation but showed no PARP cleavage, likely due to high expression of inhibitors of apoptosis proteins (IAPs), such as XIAP. Conclusion: In conclusion, AP exhibits antiproliferative and cytotoxic effects in pancreatic tumor cells, potentially disrupting an autocrine/paracrine SP-NK1R feedback loop and altering metabolic resilience. Future studies should explore metabolic stress responses and investigate whether co-treatment could overcome incomplete apoptosis activation. Citation Format: Matthias Ilmer, Maximilian Viessmann, Bernhard Renz, Frank Braun, Jens Werner. Repurposing of the SP/NK1R-complex inhibitor aprepitant in hepatopancreatic malignancies [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research—Emerging Science Driving Transformative Solutions; Boston, MA; 2025 Sep 28-Oct 1; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_3):Abstract nr B023.

Abstract Pancreatic ductal adenocarcinoma (PDAC), the most common histological subtype of pancreatic cancer, is a devastating disease predicted to be the second leading cause of cancer deaths by 2040. Despite extensive molecular characterization, therapeutic targeting of this disease remains largely unsuccessful. Thus, an increased understanding of the mechanisms driving malignant features of PDAC is critical for the development of new therapeutic strategies. Of these, cancer cell survival is a central malignant event in PDAC contributing to disease initiation, progression, and response to therapy. To date, the majority of cell survival mechanisms associated with PDAC biology has highlighted the role of cytoplasmic and extracellular factors, making the role of nuclear elements understudied. Our preliminary data has demonstrated evidence of a novel mechanism regulating nuclear envelope stability, a key process contributing to cell survival. Work from our lab has shown that oncogenic KRAS, the major genetic driver of PDAC and present in ∼40% of cases, is sufficient to reduce the incidence of spontaneous nuclear envelope rupture, a measure of nuclear envelope stability. Using laser-induced nuclear envelope rupture revealed the presence of oncogenic KRAS decreases the extent of ruptures, suggesting an axis downstream of oncogenic KRAS is key for regulation of nuclear stability. Analysis of nuclear lamins, key intermediate filaments providing structure to the nuclear envelope, revealed only A-type lamins, not B-type, are associated with overall PDAC survival and enrich at the nuclear periphery downstream of oncogenic KRAS. Furthermore, BioID protein-protein interaction assays to examine the oncogenic KRAS-induced effects on nuclear repair proteins identified an increase in interaction between Lamin A and Emerin. Knock-down of either protein results in increases in nuclear envelope spontaneous ruptures. Together our findings provide a novel oncogenic KRAS-Lamin A-Emerin axis controlling the nuclear stability in PDAC, which can serve as a new therapeutic avenue to improve PDAC treatment outcomes. Citation Format: Kayla C. LaRue-Nolan, Ashley N. Sigafoos, Luis F. Flores, Kyle J . Roux, Martin E. Fernandez-Zapico. The role of Lamin A in pancreatic cancer nuclear envelope stability [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research—Emerging Science Driving Transformative Solutions; Boston, MA; 2025 Sep 28-Oct 1; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_3):Abstract nr A059.

Abstract BACKGROUND Intraductal papillary mucinous neoplasm (IPMN) is one of the two most common precursor lesions leading to the development of pancreatic ductal adenocarcinoma (PDA). IPMNs comprise a heterogeneous group of tumors with a wide range of grades and histotypes, and the emergence of single-cell RNA sequencing (RNA-seq) and multiplex digital spatial profiling have characterized unique cell populations, including dysplastic epithelial and immune cells, within the heterogeneous tumor microenvironment that carry signature gene expressions, which could be used as markers for disease progression. However, it is not clear on the heterogeneity of the epithelial and immune response of the evolution during progression of IPMN to PDA. OBJECTIVE Combining nuclear GSK-3β with oncogenic KRas mice (referred to as KNGC – KRas, nuclear GSK-3β, Cre) resulted in the development of IPMN. We have found that 4-week-old KNGC mice show progressive desmoplasia and ductal lesion development with increased M2-like macrophage infiltration. Interestingly, CX3CL1 (fractalkine), a chemokine involved in the recruitment of CX3CR1-expressing monocytes and M2-like macrophage conversion in various disease models is expressed by IPMN progenitor ductal cells. We aim to investigate expression and contribution of CX3CL1-CX3CL1 axis in the development and progression of IPMN. METHODS We utilized a newly generated CX3CL1-mCherry and well-established CX3CR1-GFP knockin/knockout mouse for crossbreeding with KNGC and KGC (KRas, GNas, Cre) for lineage tracing and function analysis by immunofluorescent staining, flow cytometry and CyTOF. RESULTS Both KNGC- and KGC-3LmCherry/+ mice harbor a large population of CX3CL1-mCherry/EPCAM+ epithelial cells as compared to 3LmCherry/+ and wildtype (WT) control mice. In KNGC and KGC mice, we show that there was a unique population of macrophages (CD45+ CD11b+ Ly6G- F4/80+ Ly6c- ) with significantly higher expression of CX3CR1 (CX3CR1Hi) that was not seen in WT mice. Significantly, Knockout of CX3CR1 in KNGC-3RGFP/GFP animals had a paucity of M2-like macrophages, reduced T regulatory cells (Tregs), substantially reduced desmoplasia and impaired development of IPMN. CONCLUSIONS The study provides important knowledge regarding the role of CX3CL1-CX3CR1 axis in recruitment and generation of M2-like macrophages, and their impact on the initiation of the immune/stroma microenvironment facilitating IPMN development. Further investigations using these models have the potential to identify new biomarkers for risk stratification and therapeutic intervention. Citation Format: Li Ding, Kaely Roeck, Easton Maeder, Cheng Zhang, Taylor Weiskittel, Esther Rodman, Mark Maynes, Bibo Zhu, Aaron Johnson, Jie Sun, Li Hu, Daniel Billadeau. Uncoupling CX3CL1-CX3CR1 Axis in IPMN Development Through Transgenic Mouse Models [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research—Emerging Science Driving Transformative Solutions; Boston, MA; 2025 Sep 28-Oct 1; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_3):Abstract nr A064.

Abstract Pancreatic adenocarcinoma (PDA) has poor response to chemotherapy with a strong likelihood of cancer recurrence. While previous studies have examined patient samples collected before and after chemotherapy, few have analyzed matched samples from the same patients that allow us to deconvolute interpatient heterogeneity, a large limitation to PDA studies. Here, we study the effects of chemotherapy on tumor cells and their surrounding microenvironment using scRNA sequencing of matched pre- and post- treatment tissue biopsies from 5 patients. We utilized the Seurat v4 pipeline to observe transcriptomic differences and corresponding putative cellular interactions in both treatment states. Unsurprisingly, we found insufficient tumor epithelial cells post-treatment due to the intended cytotoxic effects of chemotherapy, leading us to focus on the tumor microenvironment where we had sufficient cells to analyze. We identified that immune cells in the TME are heterogeneously affected by chemotherapy treatment with patient specific differences, but we did identify a unanimous increase in CXCR4 in CD4 and CD8 positive T cells after treatment. Analysis of CAFs revealed that a subset of fibroblasts lose myofibroblastic features and increasingly acquire 'neural'-like features after treatment. This suggests that chemotherapy-altered fibroblasts may contribute to a pro-tumor microenvironment that facilitates recurrence through neuron–CAF–tumor interactions. Through inferred ligand-receptor pairs identified with the CellChat v2 pipeline, we observed that increased CXCL12 in these neural CAFs interacts with the increased CXCR4 on T-cells. We validated the expression of these genes in patients by staining human patient PDAC tissues (both treated and treatment naïve tissues) for neural genes that were highly enriched post-treatment in our single cell sequencing dataset. We have also begun inhibiting these genes of interest in CAFs and are exploring the effects of these ‘neural’-CAFs on patient-derived tumor organoids in culture. Citation Format: Aylin Z. Henstridge, Padma Kadiyala, Ahmed Elhoissiny, Jianhua Liu, Georgina Branch, Nandini Arya, Vaibhav Sahai, Nicole Peterson, Jorge Machicado, Richard Kwon, Allison Schulman, Erik Wamsteker, George Phillips, Martin Fernandez-Zapico, Mark Truty, Timothy Frankel, Fillip Bednar, Marina Pasca di Magliano, Costas Lyssiotis, Eileen S. Carpenter. An increase in neural cancer associated fibroblasts following exposure to chemotherapy in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research—Emerging Science Driving Transformative Solutions; Boston, MA; 2025 Sep 28-Oct 1; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_3):Abstract nr B079.

Abstract Introduction: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with limited treatment options and poor survival. This study explores how a medically supervised ketogenic diet (MSKD) impacts the gut microbiome and treatment response in patients with newly diagnosed metastatic PDAC receiving gemcitabine, nab-paclitaxel, and cisplatin chemotherapy. Methods: As part of a randomized Phase II trial, 32 evaluable patients (median age 65.9 years; 53% male), 16 were randomized to either MSKD or standard diet (SD) combined with chemotherapy. Stool samples were collected from 4 patients in the MSKD group (13 samples) and 8 patients in the SD group (23 samples). Deep shotgun metagenomic sequencing was conducted using NovaSeq (Illumina). Taxonomical and functional microbiome characterization was performed using MetaPhlAn 4.0 and HUMAnN 3.6 (The Huttenhower Lab, Harvard). Comprehensive bioinformatics analyses, using QIIME2, were performed to analyze microbiome composition and function over time. Results: Patients in the MSKD group showed better treatment responses overall. Microbiome profiles between the two groups remained distinct throughout therapy. Though not statistically significant due to sample size, MSKD patients showed lower alpha diversity (Shannon diversity; p-value=0.1339), likely reflecting reduced intake of fermentable fiber. Differential abundance analysis using the ANCOM-BC method revealed a significant enrichment of beneficial taxa in the MSKD group compared to the SD group (p<0.05, log-fold change [lfc]≥2), including Akkermansia muciniphila (linked to improved response to immune checkpoint inhibitors; p=0.017931, q=1), Intestinimonas butyriciproducens (a short-chain fatty acid [SCFA] and butyrate producer; p=3.09E-05, q=0.017), and Streptococcus thermophilus (a supporter of gut mucosal health; p=1.15E-05, q=0.006). During the course of the study, only MSKD patients showed sustained increases in Roseburia hominis (SFCA/butyrate producer; p=3.94E-05, q=0.021) and Lacticaseibacillus rhamnosus (with anti-inflammatory and immune-modulating properties; p=7.28E-19, q=3.98E-16), along with a marked reduction in potentially pro-inflammatory Actinomyces spp.(p≤4.47E-05, q≤0.024). Functional profiling showed increased abundance of cancer-relevant microbial pathways in MSKD patients, including phosphatidate metabolism (PWY-7039; involved in lipid signaling and immune regulation; p=4.36E-04, q=0.20) and allantoin degradation (PWY-5705; linked to redox balance; p=9.16E-06, q=0.004). Conversely, L-ascorbate biosynthesis V (PWY-6415) was reduced (p=3.80E-04, q=0.17), likely due to decreased D-galacturonate substrate availability from fiber restriction. Conclusion: These findings suggest that an MSKD may beneficially modulate the gut microbiome in ways that support and enhance therapeutic response in patients with PDAC. Further validation in a larger cohort is warranted to confirm these results and improve analytical resolution. Citation Format: Keehoon Lee, Derek Cridebring, Gayle S. Jameson, Denis J. Roe, Erkut Borazanci, Diana L. Hanna, Caroline G.P. Roberts, Meredith S. Pelster, Richard C. Frank, Angela T. Alistar, Alan M. Miller, J. Erin Wiedmeier-Nutor, Sandra D. Algaze, Alison R. Zoller, Sarah J. Hallberg, Betsy C. Wertheim, Joshua D. Rabinowitz, Stephen Gately, Jennifer Keppler, Sunil Sharma, Drew W. Rasco, Daniel D. Von Hoff. Ketogenic Diet Modulates Gut Microbiome Composition and Enhances Treatment Response in Patients with Advanced Pancreatic Cancer: A Phase II Study [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research—Emerging Science Driving Transformative Solutions; Boston, MA; 2025 Sep 28-Oct 1; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_3):Abstract nr B094.

Background: Ankle arthroscopy (AA) is a commonly used operative technique to diagnose and treat a variety of intraarticular pathologies of the ankle joint. In AA, 2 portals are commonly established to achieve visualization of the joint: the anteromedial (AM) and anterolateral (AL) portals. However, the superficial peroneal nerve (SPN) runs near the anterolateral portal site; thus, creation of the AL portal is associated with neuropraxic injuries to the SPN. When AA is combined with additional procedures, such as a Brostrom-Gould ligament repair or open reduction internal fixation (ORIF), the use of a direct lateral incision is required. We present a novel approach to combining AA with lateral adjunct procedures which avoids creation of the AL portal; the AM portal and lateral incision are used for instrumentation instead. The primary objective of this study is to compare complication rates, such as SPN injury, between the lateral incision (LI) approach and conventional arthroscopy plus a lateral incision approach. Methods: Following IRB approval, a retrospective chart review was conducted spanning a time frame from January 2020 to October 2024. Patients were included if they underwent AA plus either a Brostrom-Gould repair or ORIF (AA+) or if they underwent AA plus adjunct procedures using the lateral portal instrumentation method (LI). Ninety-four patients were initially identified; 2 were excluded per criteria. Demographic information, intraoperative details, and any postoperative complications or reoperations were recorded. Descriptive statistics were used to describe demographics and operative data, and 2-tailed Student t tests were used to identify statistical differences between group metrics. Results: Ninety-two patients were included in the study. No statistical differences were observed between cohorts in either of the intraoperative metrics considered (procedural duration and tourniquet duration; P = .44 and .89, respectively). In addition, complication and reoperation rates were not statistically different between the LI and AA+ groups ( P = .94 and .40, respectively). The rate of SPN neuropathy or neurapraxia were also compared between groups, resulting in no statistical differences ( P = .37). Conclusion: In this retrospective cohort study, we observed no differences when only anteromedial and lateral portals are used for an ankle arthroscopy with adjunct procedures compared with the traditional 3-incision approach. We hypothesize that instances of infection or wound dehiscence would decrease given a large enough cohort because of the creation of 1 fewer portal. However, given the small, underpowered sample, we cannot determine whether the lateral approach alters complication risk; larger multicenter studies are needed. Level of Evidence: Level III, retrospective cohort study.

Objective: Target vessel stenosis or occlusion is a common indication for secondary intervention after fenestrated-branched endovascular aortic repair requiring long-term imaging surveillance including duplex ultrasound (DUS). This study aimed to describe and compare longitudinal changes in peak systolic velocity (PSV) measurements for renal and mesenteric arteries targeted by directional branches (DBs) or reinforced fenestrations (RFs). Methods: Patients enrolled in a prospective, nonrandomized study (2013-2020) had DUS of celiac axis, superior mesenteric artery, and renal arteries (RAs) obtained preoperatively, at 6 to 8 weeks, 6 months, and annually. Vessels with preprocedural stenosis were excluded. Outcomes were variations in PSV over time for target vessels incorporated by DBs or RFs, differences in balloon-expandable stent-grafts (BESGs) and self-expandable stent-grafts (SESGs), PSV measurements prior to secondary interventions related to vessel stenosis, and a predictive value of PSV for stenosis requiring secondary intervention. Results: A total of 419 patients (292 male, mean age 74 ± 8 years old) were enrolled, with 1,311 target vessels analyzed preoperatively, including 607 mesenteric and 704 RAs. Over a median follow-up of 23 months (interquartile range [IQR], 7-36), PSV measurements decreased in the first 6 to 8 weeks after DB incorporation, remained stable, followed by a nonsignificant increase at 5 years. PSV increased in the first 6 months using RFs with postoperative velocities significantly higher ( P < .05) for RFs compared to DBs. Branched mesenteric vessels stented with BESGs had higher velocities than SESGs ( P < .05). Of the 23 target vessels treated by secondary intervention for stenosis, 19 (83%) had velocities above the thresholds for native, nonstented vessels. Furthermore, in RAs (n = 20) PSV effectively predicted clinically relevant stenosis, AUC was 0.98, with a 231 cm/s threshold offering 84% sensitivity with 100% specificity. Conclusion: Longitudinal follow-up shows that velocity changes vary depending on the type of incorporation, vessel, and bridging stent. For DBs, PSV decreased initially, stabilized, and showed a nonsignificant increase at 5 years. In contrast, PSV increased with RFs and remained higher than DBs. Despite these variations, velocities remained below established thresholds for clinically significant stenosis in nonstented vessels. Criteria for in-stent stenosis may differ, and PSV alone should not be the sole indicator for reintervention. Clinical Impact This study provides new insight into duplex ultrasound (DUS) surveillance after fenestrated and branched endovascular aneurysm repair (FB-EVAR). Peak systolic velocity (PSV) trends differed between fenestrations and branches, and stent type influenced flow dynamics. Importantly, most vessels with secondary interventions had elevated PSVs, but many others exceeded native stenosis thresholds without clinical consequence. Despite these variations, velocities remained below established thresholds for clinically significant stenosis in non-stented vessels. Criteria for in-stent stenosis may differ, and PSV alone should not be the sole indicator for reintervention.The reported PSV measurements served as a benchmark for DUS surveillance following FB-EVAR.