Citations

Abstract Introduction: Detectable circulating tumor DNA (ctDNA) is associated with inferior outcomes in Ewing sarcoma (ES); however, ctDNA clears in nearly all patients within 2 of the 6 chemotherapy cycles before radiotherapy (RT) or surgery. Given a 3-year EFS of 37% on AEWS 1221 (metastatic) and 5-year EFS of 78% on AEWS 1031 (localized), current ctDNA testing fails to predict most relapses. Extracellular vesicles (EVs) are microscopic particles studied as a biomarker in multiple cancer types. We hope to improve the sensitivity of ctDNA in ES and provide the first application of EVs in ES. Methods: cfDNA was isolated from 1mL plasma, quantified by Qubit, and sequenced as NEBNext Enzymatic Methyl-seq v2 libraries. We performed a systematic unsupervised clustering analysis of 27 ES plasma cfDNA profiles using 4 differentially methylated regions (DMR) subsets (63 strong DMRs, top 30, top 15, and 10 promoter-proximal loci), 3 clustering algorithms (k-means, Ward hierarchical, PAM), and k=2-5 clusters, testing associations with tumor burden and progression. EV analysis involved antibody detection against ES surface markers, including LINGO1, ENPP1, CDH11, and CD99. Concentrations of EVs were determined by standardized and calibrated high-resolution flow cytometry then analyzed with custom-built software to automatically determine and apply gates. Samples were de-identified, randomly coded, and run in triplicates. The senior research technologist responsible for EV analysis was blinded to patient information and clinical data. Results: EV analysis included 36 pre-RT samples from 16 metastatic and 20 localized ES patients from a prospectively maintained biobank, with 27 pre-RT samples in the cfDNA analysis and 19 healthy donor (HD) samples. 35 of 36 patients had chemotherapy before sample collection. cfDNA concentrations were markedly elevated in ES patients compared with HD (24.4 vs 4.6 ng/mL, p<0.0001), and 74% of ES samples exceeded the HD 95th-percentile detectability threshold (7.0 ng/mL). Across clustering configurations, ES cfDNA profiles consistently exhibited reproducible methylation substructure. One configuration (PAM clustering, k = 5, 63 strong DMRs) showed a modest but permutation-supported association with primary tumor size (nominal p ≈ 0.04; empirical p ≈ 0.03-0.04). ES samples had increased EV concentration compared to HD (p<0.001), with AUC 0.988 for distinguishing between ES and HD ENPP1 (p<0.0001). The highest ENPP1 EV values were in patients with large primary tumors (>8 cm vs. ≤ 8cm) and metastatic disease (p=0.066). Conclusions: cfDNA- and EV-based liquid biopsy provide encouraging signals for high ES detectability pre-RT. We also show the first study of EVs as a novel biomarker in ES, which may provide complementary information to ctDNA. Multimodal liquid biopsy in ES may identify candidate patients for systemic or local therapy escalation and facilitate personalized care. Citation Format: Roman O. Kowalchuk, Lilli J. Greiner, Yohan Kim, Rubia Noori, Jeffrey Szymanski, William S. Harmsen, Pradeep S. Chauhan, Adam C. Amundson, Andrea M. McMahon, Peter J. Schoettler, Wendy A. Allen-Rhoades, Stephanie F. Polites, Peter S. Rose, Kelly M. Bailey, Linda M. McAllister-Lucas, Anita Mahajan, Fabrice Lucien-Matteoni, Nadia N. Laack, Aadel A. Chaudhuri. Multimodal liquid biopsy of Ewing sarcoma reveals high sensitivity prior to radiotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1149.

BACKGROUND: Subtotal cholecystectomy is increasingly recommended as a bailout strategy for the difficult gallbladder, yet its long-term durability and the risk profile of subsequent completion cholecystectomy remain incompletely defined. STUDY DESIGN: We performed a population-based retrospective cohort study of adults undergoing laparoscopic or open subtotal cholecystectomy for acute cholecystitis from 2012 to 2021 using Healthcare Cost and Utilization Project state databases from New York and Florida. The primary endpoint was remnant cholecystitis, defined as a postoperative emergency, inpatient, or outpatient diagnosis of cholecystitis or need for subsequent cholecystectomy. Kaplan–Meier analysis estimated cumulative incidence. Secondary outcomes included completion cholecystectomy and bile duct injury requiring surgical repair. RESULTS: Among 2,682 patients (98.7% laparoscopic), the cumulative incidence of remnant cholecystitis was 13.3% during a median follow-up of 2 years (interquartile range [IQR] 0.7 to 4.1). The median time to developing remnant cholecystitis was 28 days (IQR 13 to 91), with 79.7% occurring within 6 months. Only 70 patients (2.6%) underwent completion cholecystectomy at a median of 103 days (IQR 43 to 202). Completion cholecystectomy was performed via open surgery in 47.1% of patients and was associated with a 7.1% bile duct injury rate and median length of stay of 3 days (IQR 1 to 7), compared with a 0.9% bile duct injury rate for subtotal cholecystectomy overall. CONCLUSIONS: Although remnant cholecystitis occurred in 13.3% of patients after subtotal cholecystectomy, few required completion cholecystectomy. When necessary, completion cholecystectomy was frequently open and associated with a substantially higher bile duct injury rate, supporting referral to experienced hepatobiliary centers for reoperation.

Importance The management of infectious and inflammatory lesions of the breast remains controversial. The expert panel focused on management recommendations for 3 of the most common infectious breast conditions, as very few evidence-based guidelines for the management of these conditions exist. Observations Clinicians should distinguish between infectious and noninfectious lactational mastitis (LM) because the former often requires interventions whereas the latter requires supportive care only. Patients with infectious LM often have thick fluid collections that are not amenable to aspiration and usually require a stab incision with drain placement (but no packing) to resolve the infection. Operative drainage is only required if the patient cannot tolerate an office procedure. If a phlegmon is present, antibiotics should be prescribed for at least 10 days. The diagnosis of granulomatous mastitis (GM) requires pathology confirmation with characteristic findings on core biopsy. Cystic neutrophilic granulomatous mastitis (CNGM) is a specific form of GM associated with a granulomatous reaction to Corynebacterium infection and should be empirically treated with doxycycline. For patients without findings characteristic of CNGM and no other associated bacterium identified, there is no role for empiric antibiotic use. Granulomatous mastitis cases often recur and can take up to 18 months to resolve. Patients who have GM cases with worsening symptoms should be treated with repeated intralesional steroid injections; surgical excision or repeated aspirations should be avoided. Cases refractory to intralesional steroid injection may require oral steroids or even advanced biologic agents such as methotrexate or azathioprine. Periductal mastitis with squamous metaplasia of lactiferous ducts (PDM-SMOLD) is a distinct entity from other periductal mastitis cases that can present with recurrent abscesses and should be treated with antibiotics and aspiration for fluid collections. Operative excision for PDM-SMOLD is required for those patients who present with a fistula or recurrent episodes typically using a radial incision to remove the diseased ducts within and below the nipple. Conclusions and Relevance Evidence-informed, consensus-, and expert opinion–based guidelines for the management of infectious and inflammatory conditions of the breast were developed. Clinicians can use these guidelines to appropriately manage these conditions for which clinical care often varied in the past.

ABSTRACT Purpose Malignant rhabdoid tumor of the kidney (MRTK) is a rare, aggressive tumor seen in young children. The optimal timing of resection for locally advanced tumors is not well‐defined. The purpose of this study is to evaluate modern oncologic outcomes and the impact of surgical timing. Methods A multicenter retrospective review was performed by institutions participating in the Pediatric Surgical Oncology Research Collaborative. Children younger than 21 years old with MRTK diagnosed between 2000 and 2022 were included. Results Sixty‐nine patients were identified with MRTK and met the inclusion criteria. Median age of diagnosis was 10.1 months. Overall survival (OS) at 1, 5, and 10 years was 49%, 32%, and 19%, respectively. Patients with local Stage III disease who underwent upfront resection ( n = 18) compared to those who had delayed resection after NAT ( n = 15) had a similar OS, median OS greater than 60 months versus 14.6 months, respectively; p = 0.396. The surgical timing groups were balanced in terms of the presence of metastasis, length of follow‐up, and tumor characteristics. There was one occurrence of primary intraoperative tumor spill and two occurrences of organ injury in the upfront resection group compared to none in the delayed resection group. Conclusion MRTK carries a poor prognosis despite multimodal treatment. Histologic diagnosis may not be confirmed at presentation, and MRTK cannot be reliably distinguished from Wilms tumor on imaging alone. As overall survival is similar, the decision regarding surgical timing in locally advanced tumors should be individualized based on perceived resectability, balancing the risk of intraoperative complications against the possibility of tumor progression during neoadjuvant therapy.

Abstract Purpose: Standard care for high-grade gliomas (HGG) involves maximal surgical resection followed by radiation and temozolomide. Postoperative adjuvant therapy frequently causes lymphopenia, which is associated with poor prognosis. Interleukin 7 (IL7) is essential for lymphocyte development, homeostasis, and survival. NT-I7 (efineptakin alfa), a long-acting recombinant IL7, reverses lymphopenia and improves survival in murine glioma models. However, the safety, maximum tolerated dose (MTD), and impact of NT-I7 on immune cells in patients with HGG remain unknown. Patients and Methods: We conducted a phase I trial (NCT03687957) examining the MTD and effect of NT-I7 on lymphocytes in patients with newly diagnosed HGG. The primary endpoint was dose-limiting toxicity; secondary endpoints included absolute lymphocyte count (ALC) changes over time, overall response, progression-free survival, and overall survival. Exploratory endpoints included immune profiling at different time points using single-cell RNA sequencing (scRNA-seq) in a subset of patients. Results: NT-I7 was well tolerated with a MTD of 720 µg/kg. Moreover, NT-I7 significantly increased ALCs for more than 12 weeks in duration. Early elevations in CD4+, CD8+ T cells and NK cells further coincided with increased TNF and CXCL9 cytokine levels. Comprehensive immune profiling of peripheral blood T cells revealed selective clonotype expansion within CD8+, but not CD4+, T cells following NT-I7 administration. Finally, a subset of our patients with MGMT promoter–unmethylated glioblastoma, which are typically associated with a poorer prognosis, demonstrated promising clinical responses. Conclusions: NT-I7 has the potential to maintain and increase lymphocyte counts in patients with HGG and warrants further investigation, particularly in combination with immune-based therapies.

Abstract Optimal management of anticoagulation for patients with aortic mechanical heart valves (MHVs) receiving vitamin K antagonists (VKAs) undergoing gastrointestinal endoscopic procedures is clinically challenging. Risk of bleeding from an unanticipated polypectomy or biopsy further complicates this issue. Current guidelines on use of bridging with low-molecular-weight heparin (LMWH) for these procedures are based on low-quality evidence. We conducted a subanalysis of a retrospective, multicenter observational study of adult patients with aortic MHVs receiving VKAs who underwent elective gastrointestinal endoscopies (colonoscopy or upper endoscopy). We included patients who underwent the procedure between July 1, 2020, and July 1, 2023, at five centers in Canada and the United States Patients with procedures performed on separate days within a 30-day period were excluded. Efficacy and safety outcomes included thromboembolic events, major bleeding (MB), and clinically relevant non-major bleeding (CRNMB) in the 30 days post procedure. A total of 192 endoscopic procedures were analyzed. Median (interquartile range [IQR]) patient age was 66 years (58.2–72.8) and 22% were female. Warfarin was interrupted for 185 procedures (96%). Among these, 119 (64%) received LMWH bridging: 33 (17%) pre-procedure only, 10 (5%) post-procedure only, and 76 (40%) both pre- and post-procedure. Post-procedure LMWH was initiated a median (IQR) of 1 day (1–1) and discontinued 5 days post-procedure (3–8). MB occurred in two patients (1%), CRNMB in two patients (1%), and one death (0.5%) was identified; no thromboembolic events occurred. Prior to propensity score matching (PSM), post-procedure LMWH with or without pre procedure LMWH was associated with the composite outcome of MB and CRNMB (P = 0.034), although not with MB or CRNMB individually. After stepwise regression and PSM analyses, no significant differences in bleeding outcomes were observed between patients who received LMWH bridging and those who did not. Our findings indicate that although adverse thrombotic events were rare and use of post-procedure LMWH bridging was significantly associated with a small absolute increased risk of bleeding, it was not significant after PSM. Larger prospective studies are needed to better inform antithrombotic management guidelines for patients with aortic MHVs undergoing gastrointestinal endoscopy.