Invasive lobular carcinoma (ILC) is the second most common subtype of breast cancer after invasive carcinoma of no special type (NST), previously referred to as invasive ductal carcinoma. Loss of E-cadherin-mediated adhesion drives its characteristic diffuse infiltration, producing subtle or ill-defined lesions on imaging and contributing to underdiagnosis. ILC is heterogeneous, comprising a classical form and several variants-some of which, such as pleomorphic ILC, are considered more aggressive and carry distinct prognostic implications. ILC demonstrates a distinctive metastatic tropism, with a higher prevalence of peritoneal, gastrointestinal, ovarian, and leptomeningeal involvement than NST, whereas pulmonary metastases are reported less often. ILC Metastases are frequently low-volume or infiltrative and may mimic benign or inflammatory conditions, complicating staging and follow-up. This didactic review provides a head-to-toe survey of metastatic ILC, combining radiology and nuclear medicine perspectives. It highlights diagnostic pitfalls and key imaging hallmarks, with emphasis on whole-body diffusion-weighted MRI (WB-DWI) and PET/CT strategies beyond^18F-fluorodeoxyglucose ({\,}^18F-FDG), given the often low or heterogeneous FDG avidity of ILC, including^18F-fluoroestradiol (FES) and fibroblast activation protein inhibitor (FAPI) imaging. By integrating biological insights with state-of-the-art imaging, this review emphasises how the distinctive metastatic behaviour of ILC can lead to delayed detection. Increased awareness of these patterns and need for dedicated imaging approach among radiologists and nuclear medicine physicians is necessary to reduce missed or late diagnoses.

BACKGROUND: Immune checkpoint inhibitors (ICI) have transformed melanoma treatment, but reliable prognostic biomarkers are lacking. Dual-energy CT (DECT)-derived iodine concentration is a non-invasive quantitative measure of tumor vascularity. We investigated whether spatially resolved baseline iodine concentration predicts ICI outcomes in metastatic melanoma. METHODS: We retrospectively analyzed 73 patients with metastatic melanoma (614 baseline lesions) treated with ICI who underwent baseline abdominal DECT. Each lesion was partitioned into three concentric shells (core, transition zone, and rim) and iodine concentration was normalized to portal vein uptake (mNIC). Cox proportional hazards regression adjusting for lesion count and tumor volume was used to assess associations with progression-free survival (PFS). Poisson regression models were used to model new metastasis development. RESULTS: Associations between baseline mNIC and shorter PFS increased from core to periphery. After adjustment, the peripheral rim remained independently associated with shorter PFS, while the transition zone showed borderline significance. Kaplan-Meier analysis confirmed significant survival separation for peripheral rim mNIC. Organ-specific analyses demonstrated heterogeneous effects, with splenic, soft tissue, and hepatic metastases showing significant positive associations, and lymph node metastases showing a significant inverse association. Higher peripheral mNIC also predicted greater new-lesion burden through the first two follow-up examinations. Baseline mNIC was not significantly associated with progressive disease of individual baseline lesions at second follow-up. CONCLUSIONS: Peripheral tumor iodine concentration on dual-energy computed tomography independently predicts both shorter progression-free survival and greater new-lesion burden in immune checkpoint inhibitor-treated metastatic melanoma.

BACKGROUND: Primary human papillomavirus (HPV) testing has improved the sensitivity of cervical cancer screening but has lower specificity, creating a need for effective triage strategies among HPV-positive women. p16/Ki-67 dual-stained cytology has been proposed as a biomarker-based triage test that identifies HPV-associated transforming activity. OBJECTIVE: To evaluate the diagnostic accuracy of p16/Ki-67 dual-stained cytology for detecting histologically confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and grade 3 or worse (CIN3+) in HPV-positive women. METHODS: PubMed, Scopus and Web of Science were searched from inception to 1 July 2026. Eligible studies included HPV-positive women, evaluated p16/Ki-67 dual-stained cytology as the index test, used histopathology as the reference standard, and provided extractable 2 × 2 diagnostic accuracy data. Only one non-overlapping dataset per study and endpoint was retained. No missing diagnostic cells were imputed, and published adjusted non-integer estimates were retained as reported. Pooled sensitivity and specificity were estimated using a bivariate random-effects Reitsma model. Certainty of evidence was assessed using the GRADE approach. RESULTS: Twenty-seven studies were included in the main CIN2+ analysis, comprising 24,519 HPV-positive women. Pooled sensitivity for CIN2+ was 0.837 [95% confidence interval (CI) 0.804-0.866], pooled specificity was 0.643 (95% CI 0.585-0.697), and area under the curve (AUC) was 0.826. The CIN3+ analysis included 22 endpoint-specific datasets comprising 22,489 women. Pooled sensitivity for CIN3+ was 0.862 (95% CI 0.825-0.892), pooled specificity was 0.614 (95% CI 0.550-0.675), and AUC was 0.830. Integer-only sensitivity analyses produced similar estimates for CIN2+ and CIN3+, and leave-one-out analyses showed that the pooled results were not driven by any single study. Matched comparative datasets suggested that p16/Ki-67 dual-stained cytology was generally more sensitive than cytology, particularly for CIN3+, although specificity advantages were inconsistent across cohorts. The overall certainty of evidence was very low for both endpoints because of risk of bias, indirectness, heterogeneity, imprecision and limitations in the interpretation of publication bias. CONCLUSION: p16/Ki-67 dual-stained cytology showed high pooled sensitivity and moderate specificity for detecting CIN2+ and CIN3+ among HPV-positive women, which may support its potential role as a reflex triage test in HPV-based cervical screening. However, the very low certainty of evidence, heterogeneous study populations, and variable verification pathways require cautious interpretation.

Breast cancer is the most frequently diagnosed malignancy in women, and safer, more effective therapies are urgently needed. Inspired by the prenylated coumarin scaffolds of Ferulin C and Miliusol, we rationally designed and synthesized a series of novel 4-hydroxycoumarin derivatives (A, B, and PB series) to develop potent anti-breast cancer agents. Among them, lead compound PB1-3 (7-methoxy, geranyl-substituted) exhibited the most potent antiproliferative activity against MCF-7 (IC₅₀ = 3.13 μM) and 4 T1 (IC₅₀ = 4.28 μM) cells, with high selectivity over normal cells. Structure-activity relationship (SAR) analysis underscored that the combination of a methoxy group and an extended geranyl side chain is crucial for activity. Integrated computational studies (molecular docking, 100 ns MD simulations, and MM-PBSA) confirmed that PB1-3 establishes stable hydrogen-bond and hydrophobic interactions with CDK4/6. Mechanistically, PB1-3 functions as a dual-acting CDK4/6 pathway modulator: it not only directly binds to CDK4/6 but, notably, downregulates their total protein expression, thereby reducing Rb phosphorylation and inducing G0/G1 phase arrest. Concurrently, PB1-3 triggers a potent ROS burst, collapses mitochondrial membrane potential (MMP), upregulates the Bax/Bcl-2 ratio, and activates cleaved caspase-3, driving the intrinsic apoptotic cascade. In a 4 T1 orthotopic syngeneic model, PB1-3 (20 mg/kg, i.p.) significantly suppressed tumor growth comparable to cisplatin, while exhibiting excellent biosafety (LD₅₀ > 2000 mg/kg, no hepatotoxicity/nephrotoxicity) and acceptable oral pharmacokinetics (T₁/₂ = 3.0 h). Collectively, PB1-3 represents a promising prenylated coumarin lead that orchestrates both CDK4/6-Rb cell cycle checkpoint blockade and ROS-dependent mitochondrial apoptosis, offering a valuable scaffold for developing targeted breast cancer therapies, especially for TNBC.

Circulating tumor cells (CTCs) are critical biomarkers for cancer prognosis and treatment monitoring, yet their detection remains challenging due to low abundance and phenotypic heterogeneity. Herein, we developed a dual-aptamer-conjugated electrochemical cytosensor using an in situ catalase (CAT)-encapsulated nanozyme CAT@Fe(SS)MOF-EpCAM/MUC1 (CMA) with a core-shell structure (64.8% catalase encapsulation efficiency) and magnetic nanoparticles Fe3O4-EpCAM/MUC1 (FA) for highly specific CTC capture. The CMA probe achieved 85.5% aptamer grafting efficiency and exhibited enhanced peroxidase (POD)-like activity through CAT-Fe(SS)MOF synergistic catalysis, significantly amplifying the differential pulse voltammetry (DPV) signal. The cytosensor achieved a detection limit of 2 cells/mL in 1 mL of whole blood, taking 95 min, with a wide linear range from 2 to 40 cells/mL. It demonstrated high specificity toward dual-antigen-expressing CTCs and showed promising clinical utility in discriminating lung cancer patients from healthy donors. The system demonstrated good anticoagulant properties, hemolysis rates of <5%, and IC50 values of 558 μg/mL (CMA) and >700 μg/mL (FA) for RAW264.7. This novel electrochemical cytosensor offers a portable and efficient platform for CTCs detection, thereby paving the way for its meaningful integration into clinical practice.

BACKGROUND: Healing dynamics after anterior skull base (ASB) reconstruction following transnasal endoscopic surgery (TES) for sinonasal malignancies remain poorly characterized. This study aimed to describe the postoperative healing process, quantify time to healing, identify factors influencing healing, and assess radiologic evolution over time. METHODS: This multicenter retrospective study included adult patients undergoing TES with craniectomy and ASB reconstruction for sinonasal malignancies between 2016 and 2024. Serial endoscopic examinations were reviewed using a novel stage-based classification system. Postoperative contrast-enhanced magnetic resonance imaging (MRI) was analyzed to evaluate reconstruction layers, enhancement patterns, thickness changes, and brain sagging. Cumulative incidence analysis, multistate modeling, and uni- and multivariable analyses were performed to identify factors associated with healing. RESULTS: A total of 173 patients were included. Complete endoscopic healing was achieved in 15.9% of patients at 6 months, 69.9% at 12 months, and 94.4% at 24 months. Local pedicled flap reconstruction was associated with faster healing, with complete healing achieved in 89.4% of patients at 12 months compared with 60.7% in graft-based reconstructions (p < 0.001). Adjuvant radiotherapy (RT), particularly intensity-modulated proton therapy, was independently associated with delayed healing. MRI showed progressive reduction in reconstruction thickness, decreased visibility of adipose tissue and the outer graft layer, and increased brain sagging over time. RT was associated with greater remodeling changes, whereas flap-based reconstruction appeared to mitigate these effects. CONCLUSIONS: Healing after ASB reconstruction following TES is a prolonged and dynamic process influenced mainly by reconstruction technique and adjuvant RT. Local vascularized flaps promote faster and more stable healing and may be particularly advantageous in patients requiring postoperative RT.

PURPOSE: The development and progression of gliomas are intimately linked to abnormal tumor angiogenesis. Different grades of gliomas exhibit distinct vascular distribution and structural characteristics. Therefore, analyzing vascular architecture and hemodynamics can provide crucial insights into tumor growth and invasion. METHODS: Ultrasound localization microscopy (ULM) was applied to image the cerebrovascular changes in an orthotopic glioma mouse model at two different stages of tumor progression (14- and 21-days post-implantation). A total of twenty mice with intracranial glioma were imaged on the 14th day (n = 9) and on the 21st day (n = 11) after implantation. Pathological staining, vascular endothelial immunofluorescence examinations, and fluorescence dye perfusion were conducted to compare the ULM imaging results of the microvascular network morphology. RESULTS: By separating slow and fast blood flow signals, the ULM images revealed distinct vascular changes that visually correlated with H&E-derived pathological features. The vascular densities in glioma regions showed a significant increase compared to the contralateral side: 30.4% on day 14 (39.91% ± 4.09% vs. 30.60% ± 3.17%, p < 0.001) and 56.5% on day 21 (42.54% ± 3.78% vs. 27.17% ± 4.56%, p < 0.001) post-glioma implantation. The vascular densities obtained from ULM images correlated strongly and significantly with pathological and vascular perfusion results (CD31 and DiI perfusion). ULM-derived multiparametric analysis further revealed significantly reduced average vessel length in glioma regions at both Day 14 (123.72 ± 28.06 μm vs. 192.90 ± 27.75 μm, p < 0.001) and Day 21 (87.07 ± 22.92 μm vs. 233.79 ± 38.94 μm, p < 0.001), decreased blood flow velocity at Day 21 (3.70 ± 0.66 mm/s vs. 4.64 ± 0.82 mm/s, p < 0.001), and increased flow-orientation heterogeneity at both Day 14 (0.838 ± 0.082 vs. 0.595 ± 0.174, p < 0.001) and Day 21 (0.812 ± 0.086 vs. 0.625 ± 0.083, p < 0.001). CONCLUSION: ULM imaging modality enables in vivo simultaneous structural-functional imaging of glioma microvasculature at micron-level resolution, capturing microcirculatory alterations across glioma regions. Its feasibility and reliability in visualizing vascular abnormalities were validated against ex vivo pathological and vascular perfusion, providing preclinical evidence for research and clinical applications in glioma therapy assessment and aggressiveness monitoring.

Colorectal cancer (CRC) remains a leading cause of cancer mortality worldwide. 5-Fluorouracil (5-FU) is a first-line chemotherapeutic widely used in CRC treatment, but its systemic administration often causes severe toxicity due to uncontrolled biodistribution. Herein, we present near-infrared (NIR)-activated enteric prodrug microparticles, HPMCP@L-UCNPs-ONB-5-FU, which enable spatiotemporally controlled release of 5-FU in the colon. The photocleavable prodrug o-nitrobenzyl-5-fluorouracil (ONB-5-FU) is conjugated to large upconversion nanoparticles (L-UCNPs) and encapsulated within the enteric polymer hydroxypropyl methylcellulose phthalate (HPMCP) to resist gastric degradation. After oral administration, low-power 980 nm excitation yields 800 nm emission for bioimaging, whereas high-power excitation generates strong 365 nm emission that cleaves the ONB linker and locally releases active 5-FU. In vitro studies confirmed light-gated and power-dependent drug release, while cellular and orthotopic CRC studies demonstrated potent tumor inhibition with minimal systemic toxicity. Overall, this work establishes a precise and biocompatible NIR-controlled prodrug activation paradigm for oral chemotherapy of CRC.

Targeted and on-demand drug delivery technologies have attracted considerable interest for personalized cancer therapies. In this study, we developed a UV-crosslinkable and thermo-responsive gelatin methacrylate (GelMa)-poly(N-isopropylacrylamide) (PNIPAM) (G/P) hybrid hydrogel, integrated with folic acid-functionalized superparamagnetic iron oxide nanoparticles (SPIONs). Differential scanning calorimetry (DSC) and alternating magnetic field (AMF) evaluations confirmed that introducing GelMa modulated the lower critical solution temperature (LCST) to approximately 32 °C while enabling efficient magnetothermal response. Cyclic compression tests demonstrated superior mechanical properties. The 2.5G/P hydrogel achieved a compressive strength of 0.06 MPa at 78% strain, outperforming pure GelMa (0.023 MPa) and PNIPAM (0.012 MPa), with the highest modulus of elasticity at both 25 and 37 °C. In vitro biocompatibility assays using L929 fibroblasts indicated excellent cytocompatibility with >70% viability over 7 days. Furthermore, the hydrogel demonstrated excellent blood compatibility with a hemolysis ratio below 2%, complying with ISO 10993-4 standards. Synergistic reduction in cell viability was observed in human lung adenocarcinoma (NCI-H1975) and fibroblast-like osteosarcoma (MG-63) cell lines when combining drug loading and simulated AMF thermal stimulation. Triggered by hyperthermia at 41 °C, the hydrogel demonstrated a highly controlled, pulsatile 'ON/OFF' drug release profile of 5-fluorouracil (5-FU) driven by network shrinkage, achieving a maximum cumulative release of 72.6% over 28 days with a well-defined biphasic kinetic pattern. These results show that this dual-stimuli responsive hydrogel is a mechanically robust, highly efficient platform for controlled cancer therapy.

Heart failure (HF) and cancer are leading causes of global morbidity and mortality that share a significant bidirectional relationship. Epidemiologic studies reveal that cancer patients and survivors face a substantially elevated risk of HF, largely driven by cardiotoxic systemic therapies including chemotherapy, targeted therapy, immunotherapy and radiation therapy. Conversely, individuals with HF have a markedly increased incidence of cancer. This interconnection is underpinned by age and shared modifiable risk factors, including smoking, hypertension, diabetes and obesity, as well as common pathophysiological mechanisms such as chronic inflammation, neurohormonal activation, oxidative stress and dysregulated angiogenesis. Clonal haematopoiesis of indeterminate potential has emerged as a novel biological link, promoting both maladaptive cardiac remodelling and tumourigenesis. Clinically, the coexistence of HF and cancer creates complex management challenges, as each condition worsens the prognosis of the other and limits therapeutic options. In addition to providing a broad overview of the topic, this review incorporates three aspects that are underexplored in existing cardio-oncology literature-management of advanced metastatic cancer in patients with HF, use of advanced HF therapies in patients with cancer and disparities in cardio-oncology care and clinical trial representation. Effective management of patients with HF and cancer requires a multidisciplinary cardio-oncology approach that incorporates rigorous risk stratification, early detection using serial cardiac biomarkers and imaging and personalised management tailored to cancer treatment. Irrespective, cancer patients with HF have a poor prognosis. It is necessary to balance oncological efficacy with cardiovascular safety while providing a clear definition of the goals of care. Early integration of palliative and rehabilitative care can significantly improve patient quality of life and outcomes. Nevertheless, effective novel treatment strategies have significantly improved the overall survivorship for patients with cancer and/or HF.

Ammonia death is a recently identified form of regulated cell death with unique molecular mechanisms and prominent anticancer activity. Nevertheless, its efficacy is severely restricted by the absence of tumor-targeted ammonia delivery vehicles and poorly defined immunogenic properties. Herein, we develop a lysosome-targeted ammonia nanogenerator (denoted AlN@HA) to induce ammonia death in hepatocellular carcinoma (HCC) cells and boost HCC immunotherapy. Following CD44 receptor-mediated endocytosis, AlN@HA preferentially accumulates within lysosomes and undergoes in situ hydrolysis to produce excessive ammonia and nanoscopic aluminum hydroxide (Al(OH)). Intralysosomal ammonia overload further drives lysosomal alkalinization and membrane permeabilization, autophagic flux blockade, and mitochondrial dysfunction. This sequential signaling cascade elicits tumor cell ammonia death and triggers robust immunogenic cell death. Meanwhile, the hydrolytic byproduct Al(OH) functions as an intrinsic adjuvant to facilitate dendritic cell maturation. Additionally, ammonia-mediated neutralization of intratumor lactic acid reverses the immunosuppressive tumor microenvironment. In vivo results verify that AlN@HA-initiated ammonia death markedly suppresses local tumor proliferation and activates systemic antitumor immune responses, thereby sensitizing HCC to antiprogrammed cell death 1 immunotherapy. This study clarifies the immunological features of tumor ammonia death, establishes a lysosome-targeted ammonia delivery strategy, and highlights ammonia death as a viable synergistic modality for HCC combination immunotherapy.

Renal biopsy is an essential diagnostic tool to be considered in cancer patients, a population in whom renal dysfunction is frequent, multifactorial, and clinically significant. Accurate identification of the underlying lesion is often crucial for guiding oncologic therapy, preventing further renal decline, and improving overall outcomes. However, performing a biopsy in this vulnerable patient group requires careful evaluation of procedural risks and clinical context. This '10 Tips' paper provides a practical framework to support clinicians in selecting appropriate candidates, preparing for the procedure, and interpreting histopathological findings. Special attention is given to high-risk and end-of-life scenarios, where the balance between diagnostic benefit and potential harm becomes particularly delicate. By integrating clinical, procedural, and ethical considerations, this paper aims to promote thoughtful, patient-centred approach to renal biopsy in the complex landscape of onconephrology. Shared decision-making and multidisciplinary collaboration among nephrologists, oncologists, haematologists, and pathologists are essential.

Solid papillary carcinoma (SPC) of the breast is a rare neoplasm typically regarded as a low-grade tumor with indolent behavior. We report two cases of SPC in elderly women presenting with palpable breast masses. Preoperative imaging demonstrated BI-RADS 4 suspicious lesions, and ultrasound-guided core needle biopsy suggested a papillary neoplasm consistent with SPC. Definitive histopathological examination revealed SPC with unusual high-grade cytological features, including marked atypia, increased mitotic activity, and an elevated Ki-67 proliferation index, despite the absence of conventional invasive morphology in one case. These findings highlight a striking discordance between the typically indolent architectural appearance of SPC and cytological indicators of aggressive potential, underscoring the biological heterogeneity of this rare entity. Recognition of these atypical presentations is essential for accurate pathological diagnosis, risk stratification, and appropriate clinical management.

BACKGROUND: Glycolipid transfer protein (GLTP) is a key regulator of glycosphingolipid distribution between intracellular membranes. Although aberrant GLTP expression has been implicated in various cancers, its role in head and neck squamous cell carcinoma (HNSCC) remains unclear. METHODS: HNSCC samples from The Cancer Genome Atlas (TCGA) were stratified based on expression levels. A comprehensive bioinformatic analysis was conducted to investigate s expression, functional networks, and impact on the tumor immune microenvironment. To construct a prognostic model, a signature based on genes associated with expression was developed using univariate Cox and LASSO regression analyses, and its robustness was validated in the independent GSE41613 cohort. The role of in cell migration was further verified using wound-healing assays in HSC-3 and SCC-9 cell lines with overexpression or knockdown. RESULTS: was significantly downregulated in HNSCC tissues. Functional analysis linked to epidermal differentiation, muscle contractile processes, and immunomodulatory mechanisms, with involvement in key pathways such as the chemokine, Ras, and PI3K-Akt signaling pathways. Immune infiltration analysis revealed that, compared to the low GLTP expression group, the high GLTP expression group exhibited increased plasma cell infiltration, decreased levels of resting CD4 memory T cells and M1 macrophages, and generally lower expression of immune checkpoint genes. Based on these findings, a -related risk score model was constructed, which stratified patients into distinct prognostic groups and was validated in an independent cohort. Functional experiments demonstrated that GLTP overexpression inhibited cell migration, whereas its knockdown promoted migration, suggesting that GLTP regulates HNSCC cell motility. CONCLUSIONS: This study developed and validated a -based prognostic model that stratifies HNSCC patients into distinct risk groups. Functional experiments demonstrated that GLTP overexpression inhibited HNSCC cell migration, while its knockdown enhanced migration. These findings indicate that GLTP is involved in HNSCC progression and provide a rationale for further investigation.

BACKGROUND: Optimizing postoperative recovery for elderly gastric cancer patients is of great clinical significance. This retrospective cohort study aimed to explore the association between preoperative use of dexamethasone and postoperative outcomes in elderly patients undergoing gastric cancer resection. METHODS: In this retrospective cohort study, elderly patients who underwent gastric cancer resection were enrolled. Baseline and perioperative data including use of dexamethasone for antiemetic purpose were collected. Patients were divided into control group (no dexamethasone), low-dose group (< 10 mg) and high-dose group (≥ 10 mg) based on the dose of dexamethasone administered preoperatively on the discretion of anesthesiologists. The primary endpoint was postoperative length of hospital stay (pLOS), defined as the duration from surgery to initial discharge (prolonged pLOS referred to pLOS ≥ median pLOS of all patients). The association between perioperative dexamethasone use and prolonged pLOS were analyzed with multivariable logistic regression models. Dose-response trend test and sensitivity analysis were conducted to confirm the reliability of the findings. RESULTS: The high-dose group had significantly shorter pLOS and lower overall complication rate than the control group (10 [9-13] vs 13 [10-17] days, P = 0.010; 20.9% vs 41.9%, P = 0.011). After adjusting for multiple confounders, preoperative dexamethasone ≥10 mg was independently associated with shorter pLOS (OR 0.355, 95% CI 0.166-0.756, P = 0.007). The high-dose group showed lower risks of pulmonary infection and surgical site infection. Both dexamethasone groups had reduced incidence of acute coronary syndrome. CONCLUSION: Preoperative dexamethasone ≥10 mg was associated with improved short-term postoperative outcomes in elderly gastric cancer patients, while the dose <10 mg only correlated with lower acute coronary syndrome risk. These observational associations need further prospective validation.

OBJECTIVE: To quantify changes in incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) from cutaneous melanoma in mainland China, assess demographic drivers, and project age-standardized rates to 2030 using Global Burden of Disease (GBD) 2023 estimates. METHODS: We extracted annual estimates for 1990-2023 by sex and 5-year age group. Estimated annual percentage changes summarized age-standardized rate trends. Decomposition separated changes in absolute burden into population growth, population aging, and epidemiological change, defined as residual changes in age-specific rates after demographic effects. Bayesian age-period-cohort models projected age-standardized rates to 2030. RESULTS: From 1990 to 2023, incident cases increased from 4,657 to 16,593, and prevalent cases increased from 15,401 to 102,526. The age-standardized incidence rate increased from 0.49 to 0.79 per 100,000, and the age-standardized prevalence rate increased from 1.39 to 5.03 per 100,000, with estimated annual percentage changes of 1.39% and 4.14%, respectively. In contrast, the age-standardized mortality rate declined from 0.33 to 0.27 per 100,000, and the age-standardized DALY rate declined from 9.74 to 7.54 per 100,000. The burden shifted toward older ages, although the largest absolute numbers of cases and DALYs clustered around ages 55-59 years. Aging contributed most to rising incident cases and DALYs, whereas epidemiological change drove prevalence expansion and partly offset DALY growth. By 2030, the combined-sex age-standardized incidence and prevalence rates were projected to reach 0.88 and 5.84 per 100,000, respectively, while mortality was projected to remain nearly stable and the DALY rate to decline slightly. CONCLUSION: Cutaneous melanoma in mainland China remains uncommon but rising incidence and prevalence, alongside declining age-standardized mortality and DALY rates indicate a changing burden profile. This divergence may increase demand for longitudinal services, but it does not demonstrate improved individual survival or chronicity. Strengthened early detection, age-adapted prevention, standardized diagnosis, and long-term survivorship care are needed.

BACKGROUND: Testicular tuberculosis is a rare form of extrapulmonary tuberculosis (EPTB). Due to the nonspecific nature of its clinical manifestations and imaging features, it is often misdiagnosed as a malignant testicular tumor, leading to unnecessary radical orchiectomy. Accurate preoperative diagnosis is essential for organ preservation and appropriate antituberculous therapy. CASE: A 59‑year‑old male patient was admitted with a 4‑day history of left testicular enlargement. Pre‑admission ultrasonography suggested "a solid mass in the left testicle, suspected seminoma." Physical examination revealed enlargement of the left testicle with moderate consistency. Scrotal ultrasound, contrast‑enhanced ultrasound, and enhanced CT all supported the diagnosis of testicular malignancy. The patient underwent left radical orchiectomy. However, postoperative pathology revealed extensive acute and chronic inflammatory cell infiltration, caseous necrosis, and granulomatous inflammation within the testicular tissue, consistent with tuberculous pathology. The final pathological diagnosis was "left testicular tuberculosis." CONCLUSION: Testicular tuberculosis is an important differential diagnosis for testicular tumors. Despite advances in modern imaging techniques, atypical presentation remains highly prone to misdiagnosis. Clinicians should maintain a high index of suspicion for testicular tuberculosis in patients with atypical clinical and imaging findings of testicular masses. When feasible, obtaining tissue samples for histopathological and molecular examination preoperatively or intraoperatively may be crucial in avoiding unnecessary orchiectomy and achieving organ preservation.

BACKGROUND: Local excision (LE) has emerged as an organ-preserving option for patients with early rectal cancer, but high-risk pathological features significantly increase the risk of local recurrence. When completion total mesorectal excision (TME) is refused or medically unfeasible, combining radiotherapy, chemotherapy, and immunotherapy offers an adjuvant organ-preservation strategy in microsatellite-stable (MSS) rectal cancer. OBJECTIVES: The TORCH-LE trial aims to evaluate the efficacy and safety of combining radiotherapy, chemotherapy, and immunotherapy as an adjuvant organ-preservation strategy for patients with high-risk pathological features after local excision (LE) who refuse or are unfit for completion TME. DESIGN: This is a prospective, multi-center, single-arm, hypothesis-generating phase II trial. METHODS AND ANALYSIS: A total of 60 patients with MSS early rectal cancer who have high-risk features following LE will be enrolled. All participants will receive short-course radiotherapy (SCRT; 25 Gy in 5 fractions), followed by four cycles of capecitabine and oxaliplatin (CapeOx) plus the PD-1 inhibitor toripalimab. The primary endpoint is the 3-year local recurrence-free survival (LRFS) rate, with an expected benchmark of 95% (target two-sided 95% CI: 85.6%-98.9%). Secondary endpoints include 3-year disease-free survival (DFS) rate, overall survival (OS) rate, treatment-related adverse events, and quality of life. Follow-up will include regular imaging and endoscopic surveillance. DISCUSSION: The TORCH-LE trial explores a novel adjuvant treatment strategy for early rectal cancer patients with high-risk features who are not eligible for or decline completion TME. By combining SCRT, chemotherapy, and immunotherapy, the study seeks to reduce recurrence risk while preserving rectal function. Given the single-arm design, findings should be considered exploratory and hypothesis-generating. The findings may support a more personalized organ-preserving approach and provide a rationale for future randomized trials.

OBJECTIVE: This study aimed to identify steroid metabolism-related molecular subtypes, investigate the gene expression patterns of these subtypes, and construct a prognostic risk model as well as predict therapeutic response in gastric cancer. METHODS: We analyzed 410 TCGA-STAD and 483 GSE84437 gastric cancer samples. Unsupervised consensus clustering based on steroid metabolism-related genes identified molecular subtypes. Differential expression and functional enrichment analyses (GO, KEGG, GSEA) were performed. Prognostic genes were intersected with survival-associated genes, and a Lasso-Cox regression model was used to build a seven-gene risk score. Immune infiltration, tumor mutational burden (TMB), immune checkpoint expression, and drug sensitivity were evaluated. RESULTS: Two steroid metabolism-related gastric cancer subtypes were identified, with steroid-metabolism-poor prognosis subtype showing poorer overall survival. Differential expression analysis revealed 1,709 genes enriched in immune regulation, calcium signaling, cell adhesion, and extracellular matrix remodeling. Seven key genes (PRICKLE1, SERPINE1, APOD, RIMS1, GLP2R, CDH19, GRP) were used to construct a risk score, which correlated with advanced stage, steroid-metabolism-poor prognosis subtype subtype, and worse survival, and was an independent prognostic factor. High-risk and steroid-metabolism-poor prognosis subtype tumors displayed higher immune infiltration and immune scores, lower TMB, and upregulated immune checkpoint genes, indicating an immunosuppressive microenvironment. Drug sensitivity differed across subtypes and risk groups, suggesting potential implications for personalized therapy. CONCLUSIONS: Steroid metabolism defines molecular heterogeneity, immune features, and prognosis in gastric cancer. The seven-gene risk model provides a reliable tool for survival prediction and may guide personalized therapeutic strategies.

Pure red cell aplasia is a rare hematologic disorder characterized by severe normocytic anemia, reticulocytopenia, and absence of erythroid precursors. Since the COVID-19 pandemic, pure red cell aplasia has emerged as an uncommon post-infectious complication, likely driven by immune dysregulation. A 72-year-old man developed transfusion-dependent anemia several weeks after a mild COVID-19 infection. Laboratory evaluation revealed normocytic anemia (hemoglobin of 7.0 g/dL) with profound reticulocytopenia, and bone marrow biopsy showed markedly reduced erythropoiesis with preserved granulopoiesis and megakaryopoiesis. Secondary causes, including nutritional deficiencies, hemolysis, autoimmune disease, parvovirus B19, and hematologic malignancy, were excluded. The patient failed to respond to intravenous immunoglobulin, corticosteroids, and cyclosporine, achieving only a transient partial remission. Rituximab therapy was subsequently initiated and resulted in complete hematologic recovery and sustained remission at 1 year. COVID-19-associated pure red cell aplasia is a rare but clinically important complication. Clinicians should consider it in patients with severe post-COVID anemia, and rituximab may be effective in cases refractory to standard immunosuppressive therapy.

BACKGROUND: Patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC) have been reported to exhibit resistance to various cytotoxic agents, including fluorouracil. A preclinical study showed that trifluridine, a key active component of FTD/TPI, retained antitumor activity in 5-FU-refractory dMMR CRC cell lines. However, the efficacy of trifluridine/tipiracil (FTD/TPI), with or without bevacizumab, in patients with MSI-H/dMMR mCRC remains poorly understood. OBJECTIVES: This study aimed to evaluate the clinical efficacy and safety of FTD/TPI, with or without bevacizumab, specifically in patients with MSI-H/dMMR mCRC. DESIGN: A retrospective, multicenter observational study was conducted across 10 hospitals in Japan. METHODS: We identified patients with MSI-H/dMMR mCRC treated with FTD/TPI as second- or later-line therapy between June 2012 and January 2023. All eligible patients were divided into two groups: FTD/TPI monotherapy (FT group) and FTD/TPI combined with bevacizumab (FTB group); the safety and efficacy of the two groups were compared. Whole-exome sequencing (WES) was performed on available samples to explore genomic features associated with treatment response of FTD/TPI. RESULTS: The objective response rate (ORR) was 16.7% (95% confidence interval [CI], 3.6-41.4); median progression-free survival (PFS) was 5.5 months, and median overall survival (OS) was 11.8 months in the overall cohort. Although the median PFS was similar between the two groups (5.6 months in the FTB group and 5.2 months in the FT group, =0.34), the ORR (22.2% vs. 11.1%, =0.53), disease control rate (DCR; 88.9% vs. 55.6%, =0.77) and median OS (18.9 months in the FTB group and 7.1 months in the FT group, =0.18) were numerically better in the FTB group. WES revealed diverse genomic alterations, including those affecting DNA double-strand break repair-related genes, but no clear genomic biomarkers predictive of treatment response were identified. CONCLUSIONS: FTD/TPI, with or without bevacizumab, demonstrated favorable antitumor activity in patients with MSI-H/dMMR mCRC. These findings suggest that FTD/TPI-based treatment may represent a potentially useful treatment option for this rare population, although further studies are warranted.

BACKGROUND: Clinicians often screen for autoantibodies before initiating immune checkpoint inhibitors (ICIs) in advanced gastric cancer (GC), yet the utility of organ-specific panels remains unclear. OBJECTIVES: To evaluate the association of baseline antinuclear antibody (ANA) titers and organ-specific autoantibodies with severe immune-related adverse events (irAEs) and clinical outcomes in patients with advanced GC receiving ICIs. DESIGN: Single-center retrospective cohort study. METHODS: We retrospectively analyzed 244 patients with advanced GC treated with ICIs. Baseline ANA titers and organ-specific antibodies, including Ro52, thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb), were systematically evaluated. Associations with grade 3-4 irAEs were assessed using Firth's penalized logistic regression. Progression-free survival (PFS) was analyzed using Kaplan-Meier methods, Cox proportional hazards regression, subgroup analyses, and propensity score matching. RESULTS: The prevalence of organ-specific antibodies was low (<7%) and failed to predict toxicity. In contrast, high-titer ANA (≥1:160, 17.6% of patients) predicted grade 3-4 irAEs (OR = 7.98, 95% CI: 3.35-19.5; p < 0.001). Although the high-titer ANA group included a numerically higher proportion of PD-L1-negative tumors, exploratory survival analyses showed longer PFS in patients with high-titer ANA in univariable analysis (p = 0.038), whereas the association was attenuated after multivariable adjustment (adjusted HR = 0.60, 95% CI: 0.35-1.01, p = 0.056) and remained borderline after propensity score matching (p = 0.049). CONCLUSIONS: High-titer ANA was associated with an increased risk of severe irAEs in patients with advanced GC receiving ICIs. Its association with longer PFS was exploratory and requires prospective validation. These findings suggest that ANA titers may help baseline toxicity risk stratification, whereas routine screening for low-yield organ-specific autoantibodies may offer limited clinical utility in unselected patients.

OBJECTIVE: This study aimed to evaluate the efficacy and safety of sintilimab combined with anlotinib and chemoradiotherapy as first-line treatment for driver gene-negative oligometastatic non-small cell lung cancer (NSCLC). METHODS: This retrospective study included patients with driver gene-negative oligometastatic NSCLC (single organ, ≤2 lesions) treated at the Affiliated Zhangjiagang Hospital of Soochow University (7/2021-12/2023). All patients received 4 cycles of sintilimab plus albumin-bound paclitaxel/carboplatin and achieved partial response or stable disease. Subsequently, patients received concurrent radical radiotherapy with or without anlotinib, or continued the original regimen. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events were analyzed. RESULTS: A total of 88 patients were included: 27 in the sintilimab plus chemotherapy (SC) group, 32 in the sintilimab plus chemoradiotherapy (SCR) group, and 29 in the anlotinib plus sintilimab and chemoradiotherapy (ASCR) group. The radiotherapy group (SCR + ASCR) showed significantly longer median PFS and OS than the non-radiotherapy group (SC) (7.7 vs. 16.5 months, P < 0.001; 20.1 vs. 31.8 months, P = 0.004). The ASCR group had significantly higher 12-month PFS, 18-month OS, and 24-month OS rates than the SCR group (P = 0.005, 0.014, and 0.046, respectively). ORR and DCR were significantly lower in the non-radiotherapy group (P < 0.001 and P = 0.007). Treatment-related adverse events were manageable. CONCLUSION: In driver gene-negative oligometastatic NSCLC patients benefiting from first-line sintilimab plus chemotherapy, adding concurrent radical radiotherapy significantly improved survival with acceptable toxicity. The addition of anlotinib further enhanced long-term outcomes. These findings are preliminary and require prospective validation.

BACKGROUND: Early-stage testicular cancer is highly curable; however, overtreatment may result in substantial long-term toxicity. Current guidelines aim to balance relapse risk and treatment-related morbidity, yet real-world adherence remains unclear. OBJECTIVES: To assess real-world management of clinical stage (cS) I and cSIIA testicular cancer in specialized centers and to evaluate the extent to which guideline recommendations are implemented or deviated from to avoid overtreatment. DESIGN: Multicenter questionnaire-based cross-sectional study. METHODS: A structured 17-item survey was distributed to 59 urological, medical oncology, and radiation oncology experts from the German Testicular Cancer Study Group (GTCSG) and university hospitals in Germany and Switzerland. Survey topics included staging, repeated imaging, and treatment strategies for seminoma and non-seminomatous germ cell tumors (NSGCT) in cSI and cSIIA with negative serum tumor markers (S0). Statistical analyses were performed using descriptive statistics and chi-square testing. RESULTS: Fifty-three questionnaires (89.8%) were evaluable. Although current guidelines recommend active surveillance as the preferred management for cSI seminoma, irrespective of risk factors, 52.9% of institutions administered adjuvant therapy in patients with risk factors. For cSI NSGCT, only 11.5% always applied active surveillance, independent of risk factors, despite guideline-supported recommendations for this approach. In cSIIA seminoma, 43.4% routinely repeated staging imaging prior to treatment initiation, although this strategy is not uniformly guideline endorsed. Conversely, only 31.4% consistently repeated imaging in cSIIA NSGCT, despite explicit guideline recommendations supporting repeat imaging before treatment. Treatment decisions after repeat imaging were predominantly based on lymph node (LN) progression (⩾20% increase). Additional biomarkers such as microRNA-371 were used only in a minority of centers. CONCLUSION: Substantial discrepancies exist between guideline recommendations and real-world practice in early-stage testicular cancer management. While guideline adherence is essential to prevent overtreatment, repeated imaging in cSIIA seminoma may represent a reasonable de-escalation strategy and should be considered for consistent future guideline integration.