The global incidence of thyroid cancer (TC), particularly differentiated thyroid cancer (DTC), has increased substantially over recent decades, while cardiovascular disease (CVD) remains the leading cause of death globally. As advances in diagnosis and treatment have significantly improved long-term survival in thyroid cancer patients, attention has increasingly shifted toward non-cancer complications, especially cardiovascular morbidity and mortality. Current evidence indicates that TC survivors have a higher risk of atrial fibrillation (AF), coronary artery disease (CAD), stroke, heart failure, and other cardiovascular complications than the general population. This association appears to result from a complex interaction between shared cardiometabolic risk factors and biological pathways. Obesity, metabolic syndrome, diabetes, hypertension, and dyslipidemia promote chronic inflammation, endothelial dysfunction, and insulin/IGF signaling, which contribute to atherosclerosis and tumor progression. Thyroid hormone dysregulation provides an additional link between thyroid cancer management and cardiovascular risk. Long-term thyroid-stimulating hormone (TSH) suppression therapy may induce subclinical hyperthyroidism and increase susceptibility to atrial fibrillation, ischemic heart disease, cardiac remodeling, and vascular dysfunction. Treatment-related factors, including thyroidectomy, radioactive iodine therapy, and targeted therapies, may also contribute to cardiovascular toxicity and influence long-term cardiovascular outcomes. Importantly, cardiovascular risk is heterogeneous among thyroid cancer survivors and may vary according to thyroid cancer risk category and current disease status, the intensity and duration of TSH suppression, radioactive iodine exposure, and patient-level characteristics such as age, sex, and baseline cardiovascular risk. This review synthesizes epidemiological and mechanistic evidence linking TC and CVD, with particular emphasis on shared metabolic and inflammatory pathways, hormonal and treatment-related factors, and changes in cardiovascular risk across different phases of thyroid cancer survivorship. Recognizing these determinants may support individualized cardiovascular risk assessment and help balance the oncologic benefits of thyroid cancer treatment against its potential long-term cardiovascular consequences.

The prevalence of uterine sarcoma, typically leiomyosarcoma, is greater than previously believed, with current data indicating a risk as high as one in 770 women undergoing surgery for presumed leiomyomas (uterine fibroids). Presurgical detection of uterine sarcoma is an important clinical concern for gynecologists and gynecologic oncologists worldwide. Inadvertent minimally invasive treatment of unsuspected uterine leiomyosarcoma may delay definitive therapy or lead to disease dissemination. Contrast-enhanced MRI with diffusion-weighted imaging and apparent diffusion coefficient measurement provides high accuracy (88%-94.6%) in detecting uterine leiomyosarcoma, making radiologists valuable partners to gynecologists in risk assessment and disease management. The algorithm outlined in the Radiology 2023 MRI Evaluation of Uterine Masses for Risk of Leiomyosarcoma consensus statement has been preliminarily validated, and the authors present additional nuances to enhance its application in clinical practice.

IntroductionHepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, particularly in patients with cirrhosis. Genistein (GEN), a tyrosine kinase inhibitor with a favorable safety profile, has potential as a chemoprotective agent in high-risk populations. This study evaluated the effects of GEN in a rat model of diethylnitrosamine (DEN)-induced cirrhosis and HCC.MethodsThirty-three male Sprague Dawley rats were randomized into three groups (n=11/group): Control, HCC, and HCC+GEN. HCC was induced by weekly intraperitoneal DEN injections (70 mg/kg) for 16 weeks. From weeks 8-16, the GEN group received oral genistein (50 mg/kg/day), while other groups received vehicle. Liver tissues were examined histopathologically and immunohistochemically for HCC, caspase-9, ERK-1, α-SMA, and MMP-2. Tumor burden was calculated to reflect tumor size and number. Serum AFP, p53, and biochemical parameters were analyzed.ResultsTumor burden was significantly increased in the HCC group compared with controls and was significantly reduced by GEN treatment (p=0.002). Elevated serum AFP and p53 levels in the HCC group were significantly decreased with GEN. Although cirrhosis developed in both HCC groups, collagen deposition was significantly lower in the GEN-treated rats. GEN treatment was associated with reduced expression of ERK-1, α-SMA, and MMP-2, and increased caspase-9 expression, indicating anti-proliferative, anti-fibrotic, and pro-apoptotic effects.ConclusionsGenistein reduced tumor burden, serum tumor markers, and liver fibrosis in a rat model of HCC, supporting its potential as a chemoprotective agent in cirrhotic livers. Further dose-optimization and clinical studies are warranted.

Postoperative chemotherapy for breast cancer often leads to intestinal dysbiosis and immune suppression. Traditional Chinese medicine shows potential in regulating gut microbiota and enhancing immune function, offering a promising adjunctive therapeutic strategy.

To explore the effects of a traditional Chinese medicine compound on the recovery of intestinal bifidobacteria and CD4+ T-cell activation in breast cancer patients undergoing postoperative chemotherapy.

Female patients with newly diagnosed breast cancer were randomly assigned to a control group (triamcinolone tablets) and an observation group (control treatment plus kidney-tonifying and compound traditional Chinese medicine soup). Intestinal flora and immune indices were measured and analyzed using SPSS 22.0.

After chemotherapy, the observation group showed significant increases in bifidobacteria to 9.01±1.49 lg (CFU/g) and in CD4+ T-cell counts to 969/μL. The expression levels of peripheral blood CD4+ T cells and the differences in S2, nm23 and Her-2 indices were significant between the groups, with the observation group showing greater CD4+ T cell activation. The incidence of adverse reactions was significantly lower in the observation group (P-values: 0.002, 0.006 and 0.030). The observation group also demonstrated better control of gastrointestinal conditions and disease progression (P<0.001).

The traditional Chinese medicine compound effectively maintained intestinal flora balance, promoted beneficial bacterial growth, reduced adverse reactions and offered better therapeutic prospects for breast cancer patients.

FLT3-ITD occurs in approximately 20%-25% of cases of adult AML and is associated with increased relapse risk and shorter survival. FLT3-ITD status informs AML risk at diagnosis, but its dynamic changes during disease evolution are not well defined. We hypothesized that divergent FLT3-ITD clonal trajectories are shaped by preexisting molecular features detectable at diagnosis. We analyzed 319 intensively treated adults who were newly diagnosed with non-M3 de novo AML who experienced relapse and had paired FLT3-ITD mutation data at diagnosis and relapse. Patients were classified into four clonal evolution patterns: maintained FLT3-ITD negative (FLT3-ITD^negative), FLT3-ITD loss (FLT3-ITD^lost), FLT3-ITD acquisition (FLT3-ITD^acquired), and maintained FLT3-ITD positive (FLT3-ITD^positive). The FLT3-ITD^positive group was strongly associated with concurrent NPM1 and/or DNMT3A mutations, which were enriched compared with those in other groups (p < 0.001). ELN 2022 risk categories differed across clonal evolution patterns, with favorable-risk disease declining progressively from the FLT3-ITD^negative to the FLT3-ITD^positive group (44.3%-6.1%) while intermediate-risk disease rose correspondingly (21.2%-73.5%; both p < 0.001). With a median follow-up of 96.8 months, patients in the FLT3-ITD^acquired or FLT3-ITD^positive group had significantly inferior relapse-free and overall survival compared with those in the FLT3-ITD^negative group (p = 0.009 and p = 0.018, respectively, in univariate analyses; p = 0.001 and p = 0.006, respectively, in multivariate analyses adjusted for individual genetic risk features). Transcriptomics showed enrichment of inflammatory pathways in FLT3-ITD^positive cases that persisted after adjustment for NPM1/DNMT3A co-mutations and FLT3-ITD allelic ratio, together with an inferred monocyte-rich profile. Overall, FLT3-ITD evolution is associated with distinct genomic and transcriptomic features present at diagnosis. TRIAL REGISTRATION: 202203013RSD.

CDKN2A encodes the tumor suppressor p16^INK4a protein, inactivated in up to 50% of human cancers, most commonly through homozygous deletion (HD). CDKN2A HD carries major diagnostic, prognostic, and grading implications across several central nervous system (CNS) tumor types and subtypes, as well as in other solid neoplasms, including melanoma and mesothelioma. Screening for this deletion is therefore part of the pathologist's daily routine. Multiple approaches are currently available for detecting CDKN2A alterations. In addition to fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH), several other molecular techniques have emerged, each with distinct strengths and limitations, underscoring the need for integrated diagnostic strategies. Here, we review the current literature on the diagnostic, grading and prognostic significance of CDKN2A HD in solid tumors with a focus on CNS neoplasms. We also review the emerging evidence on the clinical impact of alternative gene inactivation mechanisms, including hemizygous deletions and point mutations, and discuss the performance and limitations of currently available diagnostic assays for their detection. We finally propose a practical diagnostic workflow for achieving a reliable CDKN2A alteration assessment to support patient management and therapeutic decision-making.

Cognitive effects of endocrine therapy (ET) in breast cancer are often subtle and may escape detection by standard neuropsychological assessments. Prospective memory (PM)-the ability to carry out intended actions-is particularly sensitive to mild cognitive changes, and crucial for autonomy and treatment adherence. This study examined the impact of ET, administered without chemotherapy, on PM using a virtual reality (VR)-based paradigm.

Thirty-eight postmenopausal breast cancer survivors treated with ET (ET+) or without ET (ET-), and 21 healthy controls were evaluated. To isolate the cognitive effects of ET, none of the patients had received chemotherapy. Participants completed standardized neuropsychological tests, self-report questionnaires, and a VR-based PM task assessing recall of event-based (EB) and time-based (TB) intentions after short (10-min) and long (10 h) delays.

Despite preserved performance on standard neuropsychological measures, ET+ patients showed significantly lower PM performance than ET- patients, specifically for TB intentions after the short delay (p.adj = .002). The prospective component of these TB intentions was particularly less frequently retrieved (p.adj = .014), despite preserved storage.

This study provides preliminary evidence suggesting that ET, independent of chemotherapy-related neurotoxicity, may be associated with alterations in PM. The pattern of PM performance in ET+ patients suggests a disruption in self-initiated retrieval processes during early consolidation, when memory traces remain labile and vulnerable to interference. The use of an immersive VR-based PM paradigm revealed subtle cognitive changes not captured by conventional assessments, underscoring the clinical value of ecologically valid tools.

The role of screening colonoscopy in older adults remains controversial because of procedural risks and limited life expectancy. We evaluated the diagnostic yield, procedural success, and safety of screening colonoscopy in patients aged ≥75 years.

We retrospectively reviewed 602 patients aged ≥75 years who underwent screening colonoscopy between January 2013 and December 2024. Patients were stratified into two age groups: 75-79 years (n=486) and ≥80 years (n=116). Baseline characteristics, procedural outcomes, and safety were compared.

Baseline characteristics were comparable between groups. The detection rates were 10.5%, 6.8%, and 0.9% for non-advanced adenoma, advanced adenoma, and colorectal cancer, respectively. Cecal intubation success was high in both groups (98.1% vs. 99.1%, p=0.454), and adequate bowel preparation rates were similar (71.2% vs. 72.4%, p=0.880). Sedation was used less frequently in patients aged ≥80 years (65.5% vs. 76.7%, p=0.013). Complications were rare (1.5%) and comparable between groups, with only mild events.

Screening colonoscopy in adults aged ≥75 years demonstrated high procedural success, substantial neoplasia detection rates, and low adverse event rates, with comparable outcomes in patients aged ≥80 years. However, overall clinical benefit should be interpreted cautiously, particularly in those aged ≥80 years, supporting an individualized approach.

The multi-target inhibition of two significant cancer drug targets, cathepsin B and human carbonic anhydrase (hCA) isoforms IX and XII has been explored. The exclusive synthesis of single isomeric structure of final compounds despite two possibilities, in vitro biological studies, in silico molecular docking, DFT and ADMET studies of a small library of 28 new benzenesulfonamides incorporating the 1,2,3-triazolylpyrazole motif are reported. The tumor-associated isoforms hCA IX and hCA XII have been remarkably inhibited in the low nanomolar range, while enzymatically important off-target isoforms hCA I and II were weakly inhibited by most of the synthesized sulfonamides. Overall, respectively, three (K_I < 25 nM) and two compounds (K_I < 5.7 nM) showed better inhibition of hCA IX and XII as compared with reference drug acetazolamide. Compound 9f exhibited 35-fold and eightfold better hCA I/IX and hCA I/XII inhibition selectivity, respectively, as compared with SLC-0111. Likewise, all the synthesized compounds were also assayed for their inhibition profile against cathepsin B. Some compounds exhibited better inhibition of cathepsin B as compared with reference compound curcumin. In vitro cytotoxicity studies targeting non-cancerous Vero cells (green monkey kidney cells) and cancerous A549 cells (human lung adenocarcinoma cells) have also been performed, which showed interesting results.

Salivary duct carcinoma is an aggressive salivary gland malignancy in which systemic therapy is often guided by androgen receptor and HER2 status. Treatment options are limited for HER2-negative disease after progression on androgen-deprivation therapy and chemotherapy, particularly when active central nervous system (CNS) involvement develops.

A 62-year-old man with androgen receptor-positive, HER2-negative salivary duct carcinoma developed progressive intracranial dural metastases involving the left temporal and occipital regions after surgery, adjuvant radiotherapy, androgen-deprivation therapy, and multiple chemotherapy-based regimens. The dominant lesion was a 33.6-mm left temporal dural-based mass extending across the left tentorial leaflet. Immunohistochemical profiling of archival primary tumor tissue showed high membranous TROP2 expression (H-score, 230). Off-label sacituzumab tirumotecan was initiated at 350 mg every 2 weeks without concurrent corticosteroids or local CNS-directed therapy. Serial magnetic resonance imaging demonstrated sustained regression of the dominant left temporal mass from 33.6 to 15.3 mm (-54.5%), with no new intracranial lesions. Intracranial disease control was maintained for approximately 9 months. Treatment-related Grade 2 oral mucositis and leukopenia improved with supportive care and did not require dose reduction or treatment discontinuation.

In heavily pretreated, HER2-negative salivary duct carcinoma with high TROP2 expression and progressive intracranial dural metastases, sacituzumab tirumotecan was associated with a durable intracranial response without local CNS-directed therapy. This observation supports further clinical evaluation of TROP2-directed antibody-drug conjugates in salivary duct carcinoma with CNS involvement, while the predictive value of TROP2 expression remains to be established.