Previous genome-wide association studies have identified more than 400 prostate cancer (PCa) susceptibility loci. However, the tissue and spatial epithelial contexts through which inherited PCa risk may operate in the normal prostate remain incompletely understood. We analyzed normal human prostate spatial transcriptomic data using a gsMap-based framework to localize PCa association signals across spatially resolved prostate compartments. Spatial spots were clustered using SpaGCN and then manually curated and annotated based on matched histological images and canonical prostate marker gene expression. Because individual spatial spots may contain multiple cells, annotations were interpreted as compartment-enriched dominants rather than pure cell-type identities. PCa genetic association scores were aggregated within annotated compartments using Cauchy-combined p value and median spot-level p value as a complementary descriptive summary. Gene-level spatial correspondence was further assessed using Pearson correlation coefficients (PCCs) between gene-expression patterns and spot-level PCa gsMap signal. We annotated normal prostate tissue into four major compartments: basal epithelium-enriched, luminal epithelium-enriched, smooth muscle-enriched, and fibroblast stroma-enriched compartments. Basal epithelium-enriched compartments showed the strongest and most consistent enrichment for PCa association, with a Cauchy-combined p of 1.85 × 10 and a median spot-level based p of 3.67 × 10. Luminal epithelium-enriched compartments also showed strong enrichment, with a Cauchy p of 3.79 × 10 and a median-based p of 1.45 × 10. In contrast, fibroblast stroma-enriched compartments showed no evidence of enrichment (Cauchy p = 0.52; median p = 0.42), while smooth muscle-enriched compartments showed only modest evidence in the Cauchy-based analysis that was accompanied by a weaker median spot-level association signal (Cauchy p = 8.95 × 10; median p = 0.18). PCC analysis showed that genes with the strongest spatial correspondence to PCa gsMap signal were predominantly epithelial-associated, including CDH1, VAMP8, GMNN, TSPAN1, and FOXA1. In normal human prostate tissue, inherited PCa association localizes preferentially to basal epithelium-enriched and luminal epithelial-enriched compartments rather than to smooth muscle-enriched or fibroblast stroma-enriched compartments. Gene-level PCC patterns further support spatial alignment between PCa-associated gsMap signal and epithelial transcriptional programs. These findings provide proof-of-concept evidence for the spatial localization of inherited PCa susceptibility through the integration of large-scale population-based genetic data and spatial transcriptomics.

Melanoma is a highly aggressive skin cancer with poor prognosis, often linked to excessive UV exposure. Despite advancements in immunotherapy and targeted treatments, melanoma's invasiveness and metastatic potential remain significant challenges. This study aimed to identify novel molecular targets associated with melanoma progression. Consensus clustering analysis revealed three melanoma subtypes, with the C3 subtype exhibiting the worst prognosis. Weighted gene co-expression network analysis (WGCNA) identified FOXQ1 as a key driver in this subtype. FOXQ1 expression was elevated in clinical melanoma tissues and cell lines, and silencing FOXQ1 in vitro reduced melanoma cell proliferation, migration, and induced apoptosis. To explore its downstream targets, FOXQ1 was found to repress the expression of SSBP2, a gene inversely correlated with FOXQ1. Functional assays demonstrated that silencing SSBP2 promoted melanoma malignancy. Rescue experiments showed that knockdown of SSBP2 reversed the tumor-suppressive effects of FOXQ1 silencing. These results suggest that the FOXQ1/SSBP2 regulatory axis plays a critical role in melanoma progression and may serve as a potential therapeutic target to improve melanoma treatment outcomes.

CD74, originally known as the invariant chain of Major Histocompatibility Complex Class II Molecules (MHC class II), has now been acknowledged as a versatile signaling nexus and a universal lymphoma antigen. It has a pivotal role in the maturation, stimulation, and viability of various immune cells, such as B cells, T cells, Regulatory T Cells (Tregs), monocytes, and macrophages. It is extensively and significantly expressed in a variety of hematologic cancers, encompassing acute and chronic leukemias, lymphomas, and multiple myeloma. Given its expression pattern, along with its swift internalization and limited expression in most normal tissues, CD74 emerges as a promising target for a wide array of therapeutic approaches like antibody-drug conjugates (ADCs), bispecific antibodies, and Chimeric Antigen Receptor T-cell (CAR-T) therapy. However, the downstream signaling network of CD74 is highly context-dependent, playing a dual role in physiological immune regulation and pathological pro-cancer survival.

Primary renal neuroendocrine tumors (PRNETs) are exceptionally rare neoplasms that account for less than 1% of genitourinary neuroendocrine neoplasms and pose considerable diagnostic difficulty because of their non-specific clinicoradiological presentations and diverse histomorphology, which frequently mimics conventional renal epithelial tumors. We describe two adult patients with well-differentiated PRNET managed by partial nephrectomy including a 41-year-old male with a complex bosniak category IV cystic renal lesion, and another 43-year-old female with a tumor arising from the isthmus of a horse-shoe kidney. Both tumors showed organoid, trabecular, nested, tubulocystic, and focal cribriform architecture with low mitotic activity. Case 1 additionally showed focal capsular and perineural invasion despite of low-grade morphology. Tumor cells were diffusely positive for synaptophysin, chromogranin, and CD99, and negative for PAX8, CK7, CK20, WT1, TTF1, and CDX2, with a Ki-67 index below 2% in both. Electron microscopy confirmed dense-core neurosecretory granules, and both patients remain disease-free on radioimaging based follow-up. These cases illustrate that PRNET should be considered whenever a renal mass, including a complex cystic lesion or arising in a congenital anomalous kidney, not confirming thetypical epithelial morphology, and a combined histomorphological, immunohistochemical, and ultrastructural approach with prolonged surveillance is essential for accurate diagnosis and management.

Induction of pyroptosis is a novel strategy for multiple myeloma (MM) treatment, but the underlying mechanism remains elusive. In the analysis of the transcriptomic profile in pyroptotic MM cells, we find the interferon-alpha inducible protein IFI27 is strikingly upregulated. IFI27 is downregulated in MM cells in association with poor prognosis, but its overexpression displays great potency to trigger pyroptosis in both MM cell lines and newly diagnosed MM cells in a GSDME-dependent manner. Moreover, ectopic IFI27 impairs mitochondrial structure and function. Interestingly, when mitochondria are depleted, IFI27 almost fails to induce MM cell pyroptosis. Mechanistic studies show that IFI27 recruits N-GSDME to mitochondria via BAX, therefore triggering pyroptosis. When IFI27 is knocked down, MM cells hardly undergo pyroptosis even when triggered by N-GSDME, BAX, or chemotherapeutic agents. Although GSDMD induces cell pyroptosis independent of BAX, BAX is required for IFI27- and N-GSDME-induced cell pyroptosis. Lastly, ectopic IFI27 promotes GSDME activation and triggers MM cell pyroptosis in vivo and strikingly prolongs the survival of mice with MM. In summary, the present study finds that IFI27 and BAX are essential for GSDME-mediated cell pyroptosis, and induction of IFI27 may represent a promising strategy for the treatment of MM expressing GSDME.

Targeting nanoparticles to cancer cells in vivo remains a challenge for cancer imaging. We assessed nanoparticle distribution after injecting iron oxide nanoparticles conjugated with either a monoclonal anti-HER2 (human epidermal growth factor 2), or a non-specific IgG antibody into a human HER2 overexpressing murine breast cancer model. We used Magnetic Particle Imaging (MPI) and histopathology to assess particle localization at 72 h after injection. MPI detects magnetic moments produced by magnetic particles, and histology enables spatial quantification of nanoparticles. Intratumor iron content measured by MPI correlated with inductively coupled plasma mass spectrometry (ρ = 0.868, p < 0.0001). We detected nanoparticle accumulation in tumors, and organs and tissues associated with inflammation. MPI showed higher uptake of nanoparticles in tumors, regardless of their performance in vitro. Spatial analysis showed that 43 ± 7% of nanoparticles that reached the tumor accumulated in the peripheral quartile of the tumor, with decreasing amounts toward the center. Immunohistochemical analysis showed the nanoparticles were strongly associated with inflammatory immune and stromal cells in the tumor microenvironment. This hyperintense peripheral accumulation, or ring pattern, observed with MPI enabled us to distinguish tumors from general inflammation. Iron oxide nanoparticle-mediated MPI has the potential to detect tumors, providing another powerful diagnostic tool.

Ferroptosis is an iron-dependent form of regulated cell death driven by lipid peroxidation; however, how selective autophagy regulates ferroptotic sensitivity remains incompletely understood. Here, we identify RAB8A as a selective autophagic substrate and negative regulator of ferroptosis. Quantitative proteomic analyses reveal that ferroptotic stress induces ATG5- and ATG7-dependent degradation of RAB8A. Mechanistically, ferroptotic stimuli induce RNF126-dependent polyubiquitination of RAB8A and subsequent SQSTM1-mediated autophagic degradation. Functionally, loss of sensitizes cancer cells to ferroptosis, whereas expression of the degradation-resistant active mutant RAB8A suppresses ferroptotic cell death. RAB8A interacts with TFRC and facilitates stress-induced redistribution of TFRC from the plasma membrane toward endolysosomal compartments. deficiency impairs TFRC clearance, enhances transferrin-dependent iron uptake, and increases intracellular Fe accumulation and lipid peroxidation. In fibrosarcoma and pancreatic cancer xenograft models, depletion enhances the antitumor efficacy of ferroptosis-inducing therapy. Clinically, RAB8A is upregulated and associated with poor prognosis and ferroptosis resistance in pancreatic cancer. Collectively, these findings establish an autophagy-RAB8A-TFRC axis that regulates ferroptotic sensitivity.

BACKGROUND: Spinal metastases are a common and morbid complication of advanced malignancies. While vertebral involvement is often attributed to anatomical factors, emerging evidence implicates the chemokine CX3CL1 and its receptor in guiding tumor cells to the spine and reshaping the bone microenvironment. OBJECTIVE: To systematically review the role of the CX3CL1/CX3CR1 axis in spinal metastasis from primary breast, prostate, and liver tumours, synthesizing mechanistic, preclinical, and translational findings. METHODS: Following PRISMA guidelines, we searched Medline, EMBASE, Web of Science, and Scopus from inception to May 27, 2025, identifying original studies on CX3CL1/CX3CR1 signalling in spinal metastasis. Ten studies met inclusion criteria. Data were extracted across study design, tumour model, expression analysis, mechanisms, and therapeutic or prognostic outcomes. We also analysed experimentally determined CX3CL1 and CX3CR1 structures to identify features relevant to inhibitor design. RESULTS: CX3CL1 expression was three-fold higher in spinal metastases than in primary tumours or non-spinal bone. Mechanistic studies showed roles in chemotaxis, Src/FAK and PI3K/AKT activation, EMT, vascular permeability, and immunomodulation. CX3CL1 also activated stromal pathways promoting osteolysis. Pharmacologic inhibition reduced spinal metastasis and restored chemosensitivity in murine models. Elevated serum CX3CL1/CX3CR1 levels correlated with disease burden in patient cohorts. CONCLUSION: The CX3CL1/CX3CR1 axis contributes to spinal metastasis by integrating tumour-intrinsic signalling with vertebral niche remodelling, extending the seed-and‑soil hypothesis. Its consistent activity and tractability highlight its promise as both biomarker and therapeutic target in metastatic spine disease.

PURPOSE: To determine whether intensity-modulated radiation therapy (IMRT) plan quality under a proposed facility standard of one full-time radiation oncologist supported by structured remote or part-time peer review and mandatory planning assistance is comparable to Japan's current standard requiring two full-time radiation oncologists. MATERIALS AND METHODS: In this multicenter, pair-matched, prospective trial, 41 institutional pairs were enrolled and 36 completed per protocol. Within each pair, one institution had two full-time radiation oncologists (Group A) and the other had one full-time radiation oncologist (Group B), with mandated remote or part-time peer review and planning-assistant involvement at the single-oncologist site. Common cases (prostate cancer; nasopharyngeal carcinoma [NPC] with whole-neck [WNI] or local boost [LBI] irradiation) and consensus reference contours were provided. Primary endpoints were target delineation accuracy versus the reference contour (dice similarity coefficient, DSC) and plan quality (plan quality metric, PQM; 0-100). RESULTS: Differences in DSC (Group B - A) were 0.00 (95% CI - 0.02 to 0.02) for prostate cancer, - 0.02 (- 0.06 to 0.02) for NPC-WNI, and - 0.04 (- 0.09 to 0.02) for NPC-LBI. PQM differences were 2.01 (- 2.05 to 6.07), - 3.51 (- 8.65 to 1.62), and - 2.52 (- 6.52 to 1.49), respectively. All differences fell within the pre-specified comparability margins, with no significant between-group differences. CONCLUSION: Under these benchmark study conditions, target delineation accuracy and plan quality under a single full-time radiation oncologist supported by structured remote/part-time peer review and mandatory planning assistance were comparable to Japan's two-oncologist standard, supporting the feasibility of this structured model for widening IMRT access.

The detection of pancreatic cystic lesions (PCLs) has increased markedly with the widespread use of cross-sectional imaging. Although the true proportion of intraductal papillary mucinous neoplasms (IPMNs) among PCLs remains uncertain, IPMN is considered to account for most PCLs and is a representative precursor lesion of pancreatic ductal adenocarcinoma (PDAC). However, not all PCLs should be assumed to represent IPMN, because this assumption may lead to unnecessary surveillance or overtreatment. Therefore, radiologists should first determine whether a PCL truly represents IPMN, particularly by differentiating it from lesions without malignant potential, such as serous cystic neoplasm. Once IPMN is diagnosed, appropriate risk stratification is required to identify IPMN-derived cancer, defined in this review as IPMN with high-grade dysplasia or associated invasive carcinoma. High-risk stigmata and worrisome features proposed in current guidelines are central to this assessment. However, the risk associated with each factor is not uniform; therefore, risk assessment and management decisions should consider both the number of risk factors present and the relative weight of each factor. Concomitant PDAC may also arise separately from the PCL, possibly reflecting a field defect of the entire pancreas. Unlike IPMN-derived cancer, concomitant PDAC may develop independently of cyst size or growth and is often detected at an advanced stage. Therefore, surveillance of patients with IPMN should include not only evaluation of the PCL itself and assessment for IPMN-derived cancer, but also systematic assessment of the entire pancreas for concomitant PDAC. This review discusses the differential diagnosis of PCLs, imaging assessment of IPMN-derived cancer, the concept and imaging clues of concomitant PDAC, and practical considerations for surveillance strategies.

Although ferroptosis contributes to tumor progression, the key regulators of this process in nasopharyngeal carcinoma (NPC) remain largely unknown. TRIM26, an E3 ubiquitin ligase, has not been systematically studied in NPC or ferroptosis. Ferroptosis-related NPC genes were screened using GeneCards, FerrDb, and UbiBrowser2.0 databases. TRIM26 expression in NPC cells was determined via RT-qPCR and Western blot. TRIM26 overexpression models were established in C666-1 and NPC/HK1 cells, and a ZEB1 rescue model was further constructed in C666-1 cells. Cell viability, migration, and invasion were tested using CCK-8, wound healing, and Transwell assays. Ferroptosis was evaluated using C11-BODIPY581/591 probe, malondialdehyde (MDA), glutathione (GSH), and Fe²⁺ measurements. Co-immunoprecipitation, ubiquitination, and cycloheximide chase assays were performed to investigate TRIM26 regulation of ZEB1. Dual-luciferase reporter assays and ChIP-qPCR were conducted to verify the transcriptional regulation of SLC7A11 by ZEB1. In vivo validation was conducted using a subcutaneous xenograft model. TRIM26 was significantly downregulated in NPC cells, most markedly in C666-1 cells. TRIM26 overexpression remarkably inhibited NPC cell viability, migration, and invasion. It markedly promoted ferroptosis, with increased lipid peroxidation, elevated MDA and Fe²⁺ levels, reduced GSH content, and downregulated GPX4 and SLC7A11. Mechanistic studies revealed that TRIM26 interacted with ZEB1, promoted its ubiquitination, and accelerated its protein degradation. Furthermore, ZEB1 directly regulated SLC7A11 transcription through binding to its promoter region. ZEB1 overexpression significantly reversed the ferroptotic phenotype induced by TRIM26. In vivo, TRIM26 overexpression inhibited xenograft tumor growth and activated ferroptosis, whereas co‑overexpression of ZEB1 partially attenuated these tumor-suppressive effects. TRIM26 activates ferroptosis by promoting the ubiquitination and degradation of ZEB1 protein, thereby inhibiting NPC growth and progression. The TRIM26-ZEB1 axis may represent a potential molecular target for NPC.

Radiotherapy is an effective treatment for head and neck cancer; however, it also induces alterations in healthy oral tissues. Although late radiation-induced damage has been extensively investigated, the early progression of morphological and extracellular matrix changes in the periodontal ligament (PDL) remains poorly understood. This study investigated early radiation-induced changes in collagen organisation, the type I-to-type III collagen ratio, and matrix metalloproteinase-2 (MMP-2) expression in the lingual PDL of rat incisors. Adult Wistar rats were allocated to four irradiated groups (n = 5 per group) and exposed to a single 15 Gy X-ray dose directed to the head. Animals were euthanized at 4, 9, 14, or 25 days after irradiation. A non-irradiated control group was euthanized on day 4. Left hemimandibles were fixed, decalcified, embedded in paraffin, and sectioned. Histological analyses were performed using hematoxylin and eosin, Masson's trichrome, and Picrosirius Red staining under polarized light. MMP-2 expression was evaluated by immunohistochemistry and quantified by grayscale pixel intensity analysis. Irradiation induced progressive alterations in the lingual periodontal ligament. Fibroblast nuclei exhibited morphological features consistent with cellular injury beginning on day 4, with increasing changes at subsequent time points. These changes were accompanied by progressive disorganisation of collagen bundles, increased interfibrillar spaces, and loss of normal extracellular matrix architecture. Picrosirius Red analysis demonstrated a reduction in the type I-to-type III collagen ratio on days 4, 9, and 14 after irradiation, supporting the morphological changes observed with H.E and Masson's trichrome staining. MMP-2 expression increased significantly on day 4, reached its highest level on day 9, and then progressively decreased on days 14 and 25. A single dose of X-ray irradiation induces early morphological and extracellular matrix alterations in the rat incisor periodontal ligament. The temporal association between increased MMP-2 expression, collagen fibre disorganisation, and a decreased type I-to-type III collagen ratio suggests that MMP-2 is associated with the early extracellular matrix remodelling observed on days 4 and 9 after irradiation. The subsequent decline in MMP-2 expression was accompanied by an apparent partial restoration of collagen fibre organisation on days 14 and 25.

OBJECTIVE: Prostate cancer (PCa) remains a leading cause of cancer-associated morbidity among men globally. Although enzalutamide (ENZ), a second-generation androgen receptor (AR) antagonist, serves as a mainstay therapy for castration-resistant prostate cancer (CRPC), therapeutic resistance inevitably emerges. This underscores an urgent demand for innovative treatment strategies. METHODS: CCK-8, colony formation, EdU staining, flow cytometry, Hoechst 33,258 staining, western blotting, proteomics analysis, and senescence-associated β-galactosidase (SA-β-gal) staining were performed to reveal the role and underlying mechanisms of S.C in ENZ-resistant prostate cancer. Target prediction, molecular docking, and cellular thermal shift assay (CETSA) were used to identify the target of S.C. Finally, the impact of S.C in vivo was evaluated using ENZ-resistant xenograft models. RESULTS: Our results showed that S.C effectively suppresses cell viability in ENZ-resistant models through the dual induction of apoptosis and cellular senescence. Database mining, molecular docking, and CETSA identified AR as a putative target of S.C, which was subsequently validated in vivo. S.C treatment significantly inhibited the AR signaling pathway and suppressed tumor growth in ENZ-resistant xenograft models. CONCLUSION: To our knowledge, this study demonstrates that S.C could be a promising multi-mechanistic agent which can overcome ENZ resistance by targeting AR and inducing two distinct cell death pathways, offering a potential novel therapeutic strategy for CRPC.

BACKGROUND: RADICAL PC-2 (RAndomizeD Intervention for CArdiovascular and Lifestyle Risk Factors in Prostate Cancer Patients) was a pragmatic randomized controlled trial that tested whether routine referral to a cardiologist or an internist for cardiovascular (CV) risk-factor and lifestyle modification improves outcomes in patients with prostate cancer or receiving androgen-deprivation therapy. The intervention group had more favorable outcomes overall, driven by improved cholesterol control, with no differences in rates of CV death, myocardial infarction (MI), stroke, or heart failure (HF). OBJECTIVES: The authors aim to identify patient subgroups more likely to benefit from routine CV care referral. METHODS: Prespecified subgroup analyses were used to assess whether patients at higher CV risk derived greater benefit from specialist referral, with treatment-effect heterogeneity assessed using interaction tests. The first primary outcome was a hierarchical composite of CV death, MI, stroke, HF, suboptimal cholesterol, and systolic blood pressure (SBP) control, evaluated using the win ratio. The second primary outcome was time to CV death, MI, stroke, or HF. RESULTS: Among 2487 participants, treatment effect differed by baseline total cholesterol ≤4 mmol/L vs >4 mmol/L (interaction P = 0.016), with respective win ratios of 1.21 (95% CI: 0.89-1.64) and 1.75 (95% CI: 1.51-2.03), and by baseline BP status (SBP ≥130 mm Hg or diastolic BP ≥80 mm Hg vs BP <130/80 mm Hg; interaction P = 0.003), with respective subdistribution HRs (sHRs) for CV death, MI, stroke, or HF of 0.86 (95% CI: 0.61-1.21) and 4.85 (95% CI: 1.65-14.26). The interaction for diabetes did not reach statistical significance (interaction P = 0.054) although the intervention effect estimates suggested a potential difference by diabetes status, with sHRs of 0.53 (95% CI: 0.24-1.15) among participants with diabetes and 1.25 (95% CI: 0.88-1.78) among participants without diabetes. The win ratio was higher among participants with total cholesterol >4 mmol/L, and sHRs were numerically lower among those with SBP ≥130 mm Hg or diastolic BP ≥80 mm Hg and diabetes. CONCLUSIONS: Uncontrolled modifiable CV risk factors may identify patients with prostate cancer who are more likely to benefit from routine CV care referral.

BACKGROUND: Whether a laryngeal mask airway (LMA) can be safely used during liver transplantation remains unclear. However, in clinical practice, the choice of an airway device may also reflect a broader recovery-oriented perioperative strategy rather than an isolated technical substitution. METHODS: We retrospectively reviewed adult patients who underwent primary elective liver transplantation at our center between January 2024 and November 2025. The patients were grouped according to their primary intraoperative airway device (LMA or endotracheal tube [ETT]). Propensity score matching was used to reduce baseline imbalance. Intraoperative variables, postoperative airway-related events, postoperative pulmonary complications (PPCs), intensive care unit (ICU) stays, and postoperative hospital stays were compared. RESULTS: After matching, 25 and 44 patients in the LMA and ETT groups, respectively, were analyzed. The LMA group showed a higher rate of immediate airway device removal, lower rocuronium use during anesthetic maintenance, less postoperative noninvasive ventilation, less postoperative sore throat, and a shorter postoperative hospital stay. PPCs were numerically less frequent in the LMA group, but the between-group difference was not statistically significant after matching. No increase in major airway-related adverse events was observed in the LMA group. CONCLUSIONS: In carefully selected liver transplant recipients, use of LMA within a recovery-oriented perioperative context appeared feasible and was associated with several favorable early postoperative outcomes.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) exhibits heterogeneous postoperative outcomes. This study aimed to evaluate systemic immunoinflammatory biomarkers and pathological features and develop an integrated prognostic model for overall survival (OS) in patients with ccRCC. METHODS: This multicenter retrospective study initially screened 1,662 patients who underwent surgery between January 2010 and December 2024. After excluding 27 patients with substantial missing data, 1,635 were included in baseline analyses, of whom 1,429 with complete data were included in prognostic modeling. Candidate predictors identified by univariable Cox regression were selected using elastic net regression and subsequently evaluated by multivariable Cox regression. Model performance was assessed using the C-index, time-dependent area under the curve (AUC), calibration curves, and decision curve analysis. RESULTS: Sixteen variables with  < 0.20 in univariable analyses were considered candidate predictors, and 12 were retained by elastic net regression. ISUP grade, tumor necrosis, platelet count, recurrence/metastasis status, and systemic inflammation response index (SIRI) were independently associated with OS. The nomogram showed good discrimination, with C-indices of 0.849 and 0.869 in the training and internal testing cohorts, respectively. The 1-, 3-, and 5-year AUCs ranged from 0.829 to 0.897. Calibration was satisfactory, and risk stratification identified groups with significantly different survival outcomes ( < 0.001). CONCLUSIONS: An internally evaluated nomogram integrating systemic inflammatory indices and pathological features demonstrated good prognostic performance for OS in patients with ccRCC.

IMPORTANCE: Patients with prostate cancer have a high burden of cardiovascular risk factors, often suboptimally controlled, and adverse cardiovascular outcomes. OBJECTIVE: To determine whether the routine referral of patients with prostate cancer to a cardiovascular specialist to implement a systematic risk factor strategy is more likely to reduce adverse cardiovascular outcomes and improve risk factor control than usual care. DESIGN, SETTINGS, AND PARTICIPANTS: This randomized clinical trial included patients with prostate cancer from 55 sites in 8 countries between 2015 and 2025. Eligible patients were diagnosed with prostate cancer during the past 12 months; had received treatment with androgen deprivation therapy (ADT) for the first time within the past 6 months; or planned to start ADT in the next month. Patients taking a statin with a systolic blood pressure of 130 mm Hg or lower were ineligible. Data were analyzed from May 25 to August 7, 2026. INTERVENTION: Patients were allocated in a 1:1 ratio to receive usual care alone or usual care plus routine referral to an internist or cardiologist. The specialists provided a systematic intervention, including a target of systolic blood pressure of 130 mm Hg or lower and a statin medication, irrespective of the patient's cholesterol levels (even if not usual or guideline-driven practice); encourage smoking cessation; and provide guidance on diet and exercise. MAIN OUTCOMES AND MEASURES: Hierarchical composite of cardiovascular death, myocardial infarction, stroke, heart failure, suboptimal cholesterol (total cholesterol, >155 mg/dL [to convert to mmol/L, multiply by 0.0259]) and suboptimal blood pressure (systolic blood pressure, >130 mm Hg) as evaluated by the win ratio. RESULTS: The analysis included 2487 patients with prostate cancer (mean [SD] age, 68 [8] years). During median (IQR) follow-up of 5.8 (2.7-8.2) years, the win ratio in favor of the intervention was 1.60 (95% CI, 1.42-1.81), mostly attributable to lower cholesterol in the intervention group (mean difference, 12 mg/dL; 95% CI, 9-15 mg/dL) as a consequence of greater protocol-mandated statin use. Mean (SD) close-out systolic blood pressure values were 131.1 (16.9) mm Hg in the intervention group and 132.9 (18.3) mm Hg in the control group. There was no difference in time to cardiovascular death, myocardial infarction, stroke, or heart failure between groups (subdistribution hazard ratio, 1.08; 95% CI, 0.79-1.49). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, routine referral of patients with prostate cancer to a cardiovascular specialist lead to improved outcomes, specifically through better cholesterol control. However, it is uncertain whether this reduced clinical cardiovascular events. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03127631.

BACKGROUND: Heart failure therapy (HFT) is routinely continued in breast cancer survivors after recovery from anti-HER2 cancer therapy-related cardiac dysfunction (CTRCD), despite limited evidence. HER-SAFE is the first randomised trial to assess HFT withdrawal in this population. METHODS: In this open-label, multicentre, randomised controlled trial, breast cancer survivors with recovered anti-HER2 CTRCD (asymptomatic, left ventricular ejection fraction [LVEF] ≥50%, normalised biomarkers) were randomised to HFT withdrawal or continuation. Antecedent CTRCD was mild (relative global longitudinal strain [GLS] decline >15%, LVEF ≥50%), moderate (LVEF fall >10% to <50%), or severe (LVEF <40%). The primary endpoint was a moderate or severe CTRCD event over 12 months analysed by intention to treat; secondary endpoints included serial cardiac function, biomarkers, and quality of life. RESULTS: Between July 2023 and June 2025, 90 patients were randomised (all female; median age 50 years [IQR 43-59]; median 17.3 months [IQR 7.7-33.2] since CTRCD recovery; HFT predominantly renin-angiotensin system inhibitors [98%] and beta-blockers [88%]) - 46 randomised to HFT withdrawal (1 lost to follow-up) and 44 to continuation. The primary endpoint occurred in 1 of 45 with withdrawal (moderate asymptomatic CTRCD) versus 0 of 44 with continuation (between-group difference 2.2pp; 90% CI upper limit 9.4pp). No cardiovascular deaths, heart failure hospitalisations or symptomatic CTRCD occurred. Cardiac magnetic resonance-derived LVEF remained stable in both arms at 12 months (between-group difference -0.8% [-2.0 to +0.4], p=0.21). CONCLUSIONS: Among breast cancer survivors with recovered anti-HER2 CTRCD, HFT withdrawal was not associated with symptomatic events or significant between-group difference in LVEF at 12-months.

We report the case of a 75-year-old female with a history of stage IVa hypopharyngeal squamous cell carcinoma who presented with dysphagia due to cervical esophageal stricture after prior laryngopharyngectomy and cervical esophagectomy. During rigid pharyngeal dilation, an acute and uncontained cervical esophageal perforation involving the superior mediastinum occurred, leading to pneumomediastinum. This was immediately complicated by her surgically altered anatomy creating bilateral pneumothoraces, tension pneumoperitoneum, and subsequent hemodynamic instability. Prompt recognition and emergent intervention, including needle decompression, chest tube placement, exploratory laparotomy, and intensive postoperative care, stabilized the patient's condition. This case highlights the challenges in managing high-risk patients with complex airway and esophageal conditions, underscoring the importance of multidisciplinary coordination and rapid response in preventing fatal outcomes.

BACKGROUND: Thyroid cancer incidence is rising globally; however, histopathological data from Somalia are scarce, and no comprehensive characterization of resected thyroid specimens has been reported. METHODS: A retrospective review of 438 thyroidectomy specimens reported at a histopathology referral laboratory in Mogadishu, Somalia, between 2022 and 2025 was performed. Each specimen was classified as benign, borderline, or malignant according to the World Health Organization criteria. The associations between malignancy and age and sex were examined using chi-square or Fisher exact tests and unadjusted logistic regression. RESULTS: The cohort was predominantly female (90%), with a median age of 37 years. Benign lesions accounted for 366 specimens, borderline lesions for 8, and malignant lesions for 64, giving an overall malignancy proportion of 14.6%. Nodular and colloid goiters dominated the benign diagnoses, and papillary thyroid carcinoma was the most frequent malignant subtype, accounting for 50 of 64 cases. Malignancy was highest in patients aged 30 years or younger (22.2%), and the variation across age groups was statistically significant. The incidence of malignancy did not differ significantly according to sex. Among malignant tumors, the median size was 3.0 cm, and most were in the early tumor category. CONCLUSION: Benign goiter dominates thyroid surgical pathology in Mogadishu, while papillary carcinoma leads to a modest malignant burden that is proportionally greatest in younger patients. Strengthening pathology capacity, preoperative cytology, and cancer surveillance is therefore warranted.

PURPOSE: This propensity score-matched study aimed to compare survival outcomes between preoperative TACE followed by hepatectomy and upfront hepatectomy in patients with resectable hepatocellular carcinoma. PATIENTS AND METHODS: In this single-center retrospective cohort study at Viet Duc University Hospital, 304 consecutive patients with resectable HCC treated between January 2015 and October 2024 were analyzed: 168 underwent upfront hepatectomy and 136 received preoperative TACE followed by hepatectomy. Propensity score matching (PSM; 1:1 nearest-neighbor, caliper 0.01) was performed to balance pre-treatment covariates between groups. Overall survival (OS) and disease-free survival (DFS) were compared using Kaplan-Meier analysis and the Log rank test. Independent prognostic factors were identified using multivariable Cox regression. RESULTS: Median follow-up was 58.9 months. After PSM (113 matched pairs), median OS was not reached in the upfront hepatectomy group versus 62.5 months in the preoperative TACE group (P = 0.322), and median DFS was 32.0 versus 29.2 months (P = 0.056). In multivariable Cox analysis of the matched cohort, preoperative TACE was not independently associated with OS (HR 1.15, 95% CI 0.74-1.79; P = 0.526) or DFS (HR 1.19, 95% CI 0.92-1.75; P = 0.130), whereas advanced TNM stage (OS: HR 2.45, 95% CI 1.08-5.52, P = 0.032; DFS: HR 2.26, 95% CI 1.14-4.46, P = 0.019) and microvascular invasion (OS: HR 1.48, 95% CI 1.09-2.40, P = 0.007; DFS: HR 1.52, 95% CI 1.01-2.29, P = 0.035) remained independent prognostic factors. Within the TACE group, patients achieving complete pathological necrosis (n = 26) had OS and DFS comparable to upfront hepatectomy, whereas incomplete or partial necrosis was associated with significantly worse survival (P = 0.05 for OS and P = 0.01 for DFS). CONCLUSION: In this retrospective, propensity score-matched cohort, preoperative TACE was not associated with improved overall or disease-free survival in patients with resectable HCC and does not appear justified as a routine strategy in patients who are already surgical candidates. Because the analysis was retrospective and residual confounding cannot be excluded, these findings should be regarded as hypothesis-generating. Any role for preoperative TACE in selected settings, such as borderline resectability or when complete tumor necrosis is achieved, requires prospective confirmation.

INTRODUCTION: The efficacy of photothermal therapy (PTT) for hepatocellular carcinoma (HCC) is severely constrained by tumor heat resistance, which is driven by heat shock protein (HSP) upregulation, alongside the limited tissue penetration of near-infrared (NIR) laser. METHODS: An enzyme-responsive "peptide-drug" sequence (PD) was combined with gold nanorods (GNR) to construct a tumor-targeting microgel system (GNR/PD-M). The formulation was comprehensively evaluated in HepG2 cells and BALB/c nude mice bearing subcutaneous HCC xenografts, with key assessments including MMP-2-responsive drug release, in vitro cytotoxicity, mitochondrial and tumor targeting specificity, in vivo anti-tumor efficacy, and biosafety profiles. RESULTS: In both cellular and animal models, the GNR/PD-M + laser irradiation group exhibited the strongest tumor cell inhibition. Mechanistically, this treatment significantly downregulated HSP90 expression and disrupted mitochondrial function, thereby overcoming tumor heat resistance and reducing tumor cell viability. Consistently, the in vivo anti-tumor effect of GNR/PD-M + laser was markedly superior to that of the control groups. CONCLUSION: The GNR/PD-M system synergistically enhances PTT efficacy against HCC by mitochondrial targeting and heat resistance reversal, representing a promising strategy for intelligent and targeted drug delivery.

Current guidelines recommend systemic therapy for patients with Barcelona Clinic Liver Cancer (BCLC) Stage C hepatocellular carcinoma (HCC). However, this population is highly heterogeneous regarding tumor burden, vascular invasion, liver function, and performance status, enabling opportunities for individualized, multimodal strategies. We report the case of a 72-year-old male with a 10 × 7.5 cm HCC and portal vein infiltration involving both the right anterior and left portal branches, in the setting of a past hepatitis C. Due to extensive vascular invasion, the tumor board advised primary systemic therapy with dual immune checkpoint inhibition using Durvalumab and Tremelimumab. After four months of neoadjuvant immunotherapy, restaging showed a partial response with stable liver function. Due to this favorable outcome, the tumor board reassessed resectability and recommended secondary resection. The patient underwent a robotic two-stage hepatectomy with ligation of the right anterior and left portal branches (ALPPS), followed by completion left trisectionectomy 14 days later. Final pathology revealed a complete pathologic response to immunotherapy. At twelve months, the patient remained recurrence-free, with preserved liver function and improved quality of life. This case highlights the potential of neoadjuvant dual checkpoint blockade to induce tumor regression in selected patients with BCLC-C HCC, thereby expanding surgical candidacy even in the presence of macroscopic vascular invasion. Combined with advances in robotic hepatectomy, such multimodal approaches may redefine resectability criteria.