Primary epidural extraosseous Ewing sarcoma (EES) is a rare form of spinal Ewing sarcoma with soft tissue invasion of the spinal canal and neural foramen, without involvement of the bony spinal column.

The authors report the case of a 19-year-old male presenting to the hospital with a 1-month history of left leg dysesthesias and neuropathic pain, followed by acute left leg weakness evolving over 1-2 weeks. Imaging revealed an epidural lesion at L2 with extension into the left L2-3 neural foramen. The patient underwent urgent surgery given the evolving neurological deficits. Pathological analysis revealed Ewing sarcoma. He subsequently underwent chemotherapy and radiation therapy. At the 6-week follow-up, he had improvement in left leg strength without any evidence of tumor residual on imaging. A systematic review identified 80 cases of primary epidural EES. The mean age at presentation was 21.2 years, with 81.3% of patients < 30 years of age. Most patients were initially treated with surgery (86.2%), followed by adjuvant radiotherapy and chemotherapy (77.9%). Survival and progression-free survival at 1 year were 81.1% and 75.0%, respectively.

Given the rarity of primary epidural EES, defining common treatment strategies and prognostic markers is essential to guide clinical decision-making and patient counselling. https://thejns.org/doi/10.3171/CASE2635.

This study aimed to evaluate clinical characteristics, surgical management approaches, and long-term outcomes of pediatric patients with histopathologically-confirmed pancreatic solid pseudopapillary neoplasm (SPN) at a single tertiary center over 10 years.

A retrospective review was conducted of 16 pediatric patients with pancreatic SPN who were treated at the hospital between 2015 and 2025. Data on demographics, clinical presentation, imaging, surgery, pathology, and follow-up were analyzed.

Among the 16 patients, 15 were female and 1 was male, with a median age of 14 years (range: 7-16). Abdominal pain was the most frequent presenting symptom (n=12) and other presentations included jaundice, abdominal swelling, or amenorrhea, while 2 patients reported no symptoms. The pancreatic head was the most common tumor site (n=9), and the median tumor size was 5 cm (range: 1-14 cm). Surgical procedures included enucleation (n=10), distal pancreatectomy (n=3), and the Whipple procedure (n=3). Despite positive surgical margins in 9 patients, only 2 experienced local recurrence. No patients received adjuvant therapy. Postoperative complications occurred in 2 cases. One patient developed papillary thyroid carcinoma during follow-up. The median follow-up duration was 50 months (range: 2-108), and all patients were alive and all but one are disease-free at the last evaluation.

Pediatric pancreatic SPN predominantly affects adolescent girls and often presents incidentally. Surgical resection yields excellent long-term outcomes even in the presence of positive margins. Continued follow-up is essential due to potential recurrence and rare secondary malignancies.

Oxygen-sensitive optoacoustic imaging (OS OAI) and dynamic contrast-enhanced optoacoustic imaging (DCE OAI) provide complementary, noninvasive readouts of tissue physiology. OS OAI leverages multispectral detection of endogenous oxyhemoglobin and deoxyhemoglobin to generate maps of blood oxygen saturation (%sO₂), while DCE OAI tracks the in vivo pharmacokinetics of a near-infrared absorber to quantify vascular perfusion and permeability. The goal of this protocol is to present a unified OS-DCE OAI workflow that enables simultaneous assessment of oxygenation and perfusion in two widely used pre-clinical settings: orthotopic breast cancer tumors and full-thickness cutaneous wounds. In this protocol, we demonstrated OAI of mouse models of breast cancer or a laceration wound. For OS OAI, multi-slice multispectral scans are acquired at 700-875 nm to allow spectral unmixing and estimation of %sO₂. For DCE OAI, repeated acquisitions at ≤5-s temporal resolution are performed before and after intravenous bolus injection of indocyanine green (ICG), using either multispectral sampling at 700-875 nm or single-wavelength sampling at 800 nm to generate time versus OA signal amplitude curves. The development of animal models, preparation for OA imaging, OS OAI and DCE OAI acquisitions, and analyses to measure characteristics of oxygenation and vascular perfusion are detailed, along with key troubleshooting guidance for motion artifacts, superficial absorbers, and failed injections. Together, this OS-DCE OAI protocol yields an integrated functional portrait of hypoxia and vascular transport that can detect physiological changes in tumors and wounds earlier than gross anatomical measures. OS-DCE OAI is readily adaptable to other disease models.

Colorectal cancer (CRC) is characterized by profound, multi-layered heterogeneity that limits the precision of conventional single-modality clinical tools. The emergence of multimodal foundation models (MFMs) represents a conceptual paradigm shift, moving beyond static biomarkers to capture the dynamic and evolving nature of CRC. MFMs integrate histopathology, radiology, multi-omics data (including the critical regulatory layer of epigenomics), and clinical variables into shared high-dimensional representational spaces. This integration enables improved prognostication, refined molecular subtyping, and in silico simulation of therapeutic perturbations within the tumor's functional landscape, thereby supporting rational and model-driven drug development. In this review, we synthesize the rapidly expanding body of CRC-specific MFM research and critically examine the unresolved challenges that currently limit clinical translation. We place particular emphasis on the transition from correlation to causal inference, the establishment of cross-population generalizability, and the resolution of key issues related to trustworthiness and clinical interpretability. Finally, we propose an actionable roadmap outlining regulatory, data governance, and translational requirements, including the lab-in-the-loop paradigm, necessary to position MFMs as a robust and equitable framework in clinical oncology.

Lorlatinib is a third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) with high central nervous system penetration and activity against resistance mutations. Although its clinical efficacy as first-line treatment for ALK-positive advanced non-small cell lung cancer (NSCLC) has been demonstrated, its economic value within the Italian healthcare system remains to be fully established. This study evaluated the cost-effectiveness of lorlatinib compared with alectinib as first-line therapy in Italy.

A partitioned survival model with three health states (progression-free, progressed disease, and death) was developed from the Italian National Health Service and societal perspectives over a 30-year time horizon. Clinical efficacy inputs were derived from the CROWN trial and indirect treatment comparisons using network meta-analysis. Costs (2026 euros) included drug acquisition, subsequent treatments, healthcare resource use, adverse events, end-of-life care, and societal costs. Health outcomes were expressed as life-years (LYs) and quality-adjusted life-years (QALYs). Deterministic, probabilistic, and scenario analyses were conducted to assess uncertainty.

In the base case, lorlatinib was dominant over alectinib, providing higher benefits (+2.01 LYs; +1.66 QALYs) at lower costs (-€19,210 per patient). This finding was robust across pricing scenarios. Probabilistic sensitivity analysis showed an almost 98,40% probability of cost-effectiveness at Italian willingness-to-pay thresholds.

From both NHS and societal perspectives, lorlatinib represents a cost-saving and clinically superior first-line treatment option compared with alectinib for patients with ALK-positive advanced NSCLC in Italy.

The clinical impact of hepatic steatosis (HS) among patients with autoimmune liver disease (AILD) remains unclear. We aim to determine the prevalence of HS and its clinical impact on treatment response and outcomes in patients with AILD.

We systematically searched 3 electronic databases until 17 December 2025, including all studies that reported the prevalence, clinical impact, and treatment response of AILD patients with concomitant HS. The temporal trend of HS prevalence was analyzed using a quasi-Poisson regression model, with annual percent changes (APC, %) calculated.

Overall, 44 studies, comprising 19,898 patients with autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) were included. The pooled prevalence of HS in patients with AIH, PBC, and PSC was 27.3%, 32.9%, and 21.6%, respectively. HS prevalence has significantly increased among PBC patients since 2010 (APC: +37.4%). While concomitant HS was associated with a higher risk of hepatic decompensation (OR: 1.6, 95% CI: 1.3-2.1, I2=0%) and hepatocellular carcinoma (OR: 1.8, 95% CI: 1.3-2.6, I2=0%) in patients with AIH, HS did not influence the clinical outcomes in patients with PBC. Treatment response in AIH and PBC was not influenced by concomitant HS. Available data on PSC with concomitant HS were insufficient to assess its association with clinical outcomes.

AIH patients with concomitant HS had worse outcomes than those without HS; whereas HS did not influence the clinical outcomes in patients with PBC. Future research evaluating the impact of HS on PSC and overlap syndrome is much needed.

TYRO3, AXL, and MERTK (TAM receptor tyrosine kinases) represent potential therapeutic targets in metastatic colorectal cancer. Pre-clinical and clinical data are needed to explore further how TAM receptors interact with the central nervous system, which could impact brain metastases from colorectal cancer (BM-CRC).

We analyzed TAM receptor expression in established brain metastasis stem cell lines from patients with CRC (BM-SC-CRC) (RNA and protein), a local cohort of BM-CRC patients (protein), and a cohort of metastatic CRC from The Cancer Genome Atlas (TCGA) (RNA).

When orthotopically injected into mice, BM-SC-CRC derived from two patients expressed TYRO3 and Protein S (PROS1) but poorly AXL and GAS6. When we analyzed both patients' primary tumors and metastatic sites, TYRO3 and AXL proteins were expressed in all tumor sites, but hardly MERTK. AXL was located primarily in endothelial cells, and TYRO3 in tumor cells. We examined the protein expression of TAM receptors in a cohort of BM-CRC patients, considering tissue from the primary tumor (N = 85), the matched brain metastases (N = 40), and another metastatic site (N = 29). AXL was expressed through primary tumors to brain metastases, as 72.7% of samples in BM (versus 44% with TYRO3 and 53% with MERTK) had a stable (45.5%) or increased (27.2%) protein expression compared to their paired primary tumor. None of the TAM receptors or PROS1 were found prognostic in a TCGA metastatic CRC cohort (n = 80), but GAS6 was, in univariate (HR = 2.141 [95% CI 1.018-4.506], p = 0.045) and multivariate analysis (HR = 2.382 [95% CI 1.124-5.048], p = 0.024). In exploratory analysis, patients with Low AXL/High GAS6 had a poorer prognosis (p = 0.046).

The TAM receptors' ligand GAS6 and the AXL/GAS6 ratio could help to monitor patients' prognosis in metastatic CRC settings including BM-CRC. Further research is needed to validate the TAM receptors' impact on prognosis in BM-CRC.

To investigate the effect of erianin on proliferation, migration, invasion, and apoptosis of breast cancer cells and the underlying mechanisms.

Breast cancer cell lines T-47D and MCF-7 treated with 0, 12.5, 25, 50, and 100 nmol/L erianin for 12, 24, 36, 48, and 72 h were examined for cell viability using CCK-8 assay. The effects of erianin on cell proliferation, migration, invasion, senescence and apoptosis were evaluated using clone formation, wound healing, Transwell invasion, and senescence assays and flow cytometry. mRNA microarray analysis and the Enrichr database were used to explore the biological functions of erianin. Western blotting was used to detect the changes in protein expressions related to apoptosis, epithelial-mesenchymal transition (EMT), and the Wnt/β-catenin pathway.

Erianin concentration-dependently inhibited cell viability, proliferation, migration, and invasion, and promoted senescence in T-47D and MCF-7 cells. Microarray analysis identified 1064 differentially expressed genes (DEGs), including 948 upregulated and 116 downregulated genes, which were involved primarily in EMT regulation, collagen-containing extracellular matrix, calcium ion binding, the PI3K-Akt signaling pathway, the Wnt/β-catenin signaling pathway, and apoptosis. Flow cytometry confirmed that erianin concentration-dependently induced apoptosis in the breast cancer cells, upregulated the expressions of Bax and caspase-3, decreased Bcl-2 expression, and lowered the expressions of EMT-related proteins (Snail, N-cadherin, and β‑catenin) and Wnt/β‑catenin signaling proteins (TCF4, Cyclin D1, and c-Myc). In the breast cancer cells treated with 100 nmol/L erianin, the application of a Wnt/β‑catenin agonist significantly increased the proteins expressions of TCF4, Cyclin D1, and c-Myc.

Erianin inhibits proliferation, migration, and invasion and induces senescence and apoptosis in breast cancer cells possibly by suppressing the Wnt/β-catenin signaling pathway to induce cell apoptosis and reverse EMT of the cells.

Bladder cancer is a prevalent malignancy with a high recurrence rate, necessitating the identification of novel molecular targets for diagnosis and therapy. Recent studies have highlighted the role of long noncoding RNAs (lncRNAs) in cancer progression. This study aims to investigate the role of the lncRNA IDH1-AS1 in bladder cancer, focusing on its effects on tumor growth, cell proliferation, and autophagy-related protein expression. We utilized both in vivo and in vitro models to assess the impact of IDH1-AS1 overexpression and knockdown. Tumor growth was evaluated in nude mice model of bladder cancer, while cell proliferation was measured using the EDU assay. Protein expression levels of Beclin1, P62, and LC3 were determined by Western Blot analysis. Gene expression of IDH1-AS1 was quantified using quantitative polymerase chain reaction (qPCR). Overexpression of IDH1-AS1 in nude mice model of bladder cancer led to a significant increase in tumor volume and weight, whereas knockdown of IDH1-AS1 resulted in a substantial decrease in tumor size. In vitro, IDH1-AS1 overexpression significantly enhanced cell proliferation, while its knockdown reduced proliferation. Western Blot analysis revealed that IDH1-AS1 overexpression increased the levels of autophagy-related proteins Beclin1 and LC3, and decreased P62 protein levels, with contrary effects observed upon IDH1-AS1 knockdown. qPCR confirmed successful modulation of IDH1-AS1 expression in experimental groups. Our findings indicate that IDH1-AS1 promotes tumor growth and cell proliferation in bladder cancer, potentially through the regulation of autophagy-related proteins. These results suggest that IDH1-AS1 could serve as a novel biomarker and therapeutic target for bladder cancer.

Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare lung disorder characterized by autoantibodies against Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF). Whole-lung lavage is the conventional treatment, but it does not address the underlying pathophysiology. This systematic review and meta-analysis aims to further evaluate the effects of inhaled GM-CSF on gas exchange, oxygenation, and lung volume.

We conducted a systematic review and meta-analysis following PRISMA guidelines. A literature search was performed across PubMed, Embase, and the Cochrane Library from inception to October 2025. Randomized Controlled Trials (RCTs) comparing inhaled GM-CSF to a control in adult patients with aPAP were included. The primary outcomes assessed pulmonary gas exchange, oxygenation, and lung volume, while exercise capacity and dyspnea levels were secondary outcomes. Statistical analyses were performed using Review Manager (RevMan) version 5.4.1 and R version 4.5.2, with heterogeneity assessed using I² statistics.

Four phase III RCTs comprising 402 patients (224 inhaled GM-CSF, 178 control) with ≥ 25 weeks of follow-up were included. Inhaled GM-CSF significantly enhanced DLCO% predicted (MD 5.09; 95% CI 2.05 to 8.13; p = 0.001; I² = 0%) and reduced PA-aO₂ (MD - 4.25; 95% CI - 6.62 to - 1.88; p = 0.0004; I² = 0%), with corresponding increases in PaO₂. Dyspnea scores significantly improved (SMD - 0.49; 95% CI - 0.70 to - 0.29; I² = 9%). No significant improvements were observed in lung volume or exercise capacity. Continuous and intermittent regimens demonstrated comparable efficacy and side effects across subgroups.

Inhaled GM-CSF improves gas exchange, oxygenation, and dyspnea in aPAP while maintaining a favorable safety profile, indicating its potential as a noninvasive, targeted therapy.