Search Results (1,241)

Background: Accurate assessment of axillary lymph node (ALN) status after neoadjuvant therapy (NAT) remains essential for surgical planning in patients with initially node-positive breast cancer. This study evaluated the potential value of contrast-enhanced ultrasound (CEUS) in conjunction with sentinel lymph node biopsy (SLNB) for post-NAT axillary assessment and explored clinicopathologic factors associated with lymph node (LN) status. Methods: In this retrospective study, 179 patients with cytologically confirmed node-positive breast cancer underwent CEUS after NAT, followed by surgical pathological evaluation. The observed false-negative rate (FNR) of post-NAT CEUS combined with SLNB was compared with that of SLNB alone and post-NAT ultrasound (US) combined with SLNB. Univariable and multivariable generalized estimating equation (GEE) analyses were performed to identify factors associated with LN-level outcomes. Results: A total of 213 sentinel lymph nodes were analyzed. CEUS combined with SLNB had an observed FNR of 13.25% (95% CI, 7.56–22.19%), which was numerically lower than the FNRs of SLNB alone and US combined with SLNB. HER2 status, hormone receptor status, breast pathological response after NAT, and CEUS findings were significantly associated with nodal status in the univariable GEE model. Exploratory multivariable GEE analyses identified pre-NAT HER2 positivity as an independent protective factor for false-negative LN outcomes, whereas pre-NAT ER status and residual invasive carcinoma were independently associated with CEUS-negative/SLNB-positive nodal status. The exploratory models showed high apparent discrimination, with AUCs of 0.941 (95% CI, 0.890–0.991) and 0.917 (95% CI, 0.866–0.968). Conclusions: In this single-center retrospective cohort, the addition of post-NAT CEUS to SLNB was associated with a lower observed FNR than SLNB alone. These findings support the potential role of CEUS as a complementary tool for post-NAT axillary assessment but require prospective studies with external validation. Full article

Background: Right-sided metastatic colon cancer represents a clinically distinct subgroup with inferior outcomes and uncertain optimal biologic treatment selection, even among patients with RAS wild-type disease. Real-world data focusing specifically on right-sided RAS wild-type metastatic colon cancer remain limited. This study aimed to describe clinicopathologic characteristics, metastatic patterns, treatment approaches, and survival outcomes in this population using a national multicenter registry. Methods: This retrospective multicenter cohort study was conducted using data from the ONKO-KOLON Türkiye registry. Patients with pathologically confirmed KRAS/NRAS wild-type metastatic colorectal cancer and available primary tumor localization were evaluated. The main analytic cohort included patients with right-sided metastatic colon cancer, defined as right colon or transverse colon tumors. Left-sided colon cancer patients were used as a contextual comparator, while rectal cancer patients were excluded from sidedness-based colon comparisons. Survival outcomes were estimated using the Kaplan–Meier method, and prognostic factors were evaluated using Cox regression analyses. Results: Among 1079 patients in the source cohort, primary tumor localization was available in 1065 patients. Of these, 213 had right-sided colon cancer, 464 had left-sided colon cancer, and 388 had rectal cancer. In the right-sided cohort, median age was 61.5 years, 64.3% were male, and 66.7% had synchronous/de novo metastatic disease. Liver metastasis was the most common metastatic site (63.4%), followed by lymph node (31.0%), lung (21.1%), and peritoneal metastases (15.5%). First-line anti-VEGF-based treatment was used in 46.0% of patients, while anti-EGFR-based treatment was used in 40.8%. Among evaluable patients, the objective response rate was 46.8% and the disease control rate was 79.2%. Median progression-free survival was 10.0 months, and median overall survival was 24.0 months. In unadjusted exploratory analysis, median OS was 27.0 months with anti-EGFR-based treatment and 17.0 months with anti-VEGF-based treatment (log-rank p = 0.022), whereas median PFS was 10.0 months in both groups. In an extended covariate-adjusted multiple-imputation sensitivity model, the anti-EGFR OS estimate did not meet statistical significance (adjusted HR 0.66, 95% CI 0.43–1.00; p = 0.051). In a secondary contextual comparison, median overall survival was shorter in the right-sided than in the left-sided colon cancer group (24.0 vs. 28.0 months; HR 1.47, 95% CI 1.19–1.82; p < 0.001), whereas progression-free survival did not differ significantly. Conclusions: This study provides a descriptive account of metastatic patterns, treatment approaches, and outcomes in a dedicated right-sided RAS wild-type metastatic colon cancer cohort. The unadjusted OS difference between biological treatment groups was not confirmed after measured covariate adjustment and should not be interpreted as evidence of comparative treatment effectiveness. Because molecular profiling was incomplete, this study cannot identify biomarker-defined treatment subgroups. Prospective studies with complete, predefined molecular characterization are needed before molecularly informed treatment selection hypotheses can be evaluated in this population. Full article

Background: Prognostic assessment after neoadjuvant chemotherapy and curative gastrectomy remains challenging in patients with gastric adenocarcinoma because postoperative outcomes are influenced by both pretreatment disease burden and pathological response. We aimed to develop and internally validate a clinicopathological prognostic model and a simple postoperative risk classification for predicting disease-free survival (DFS). Methods: This single-center retrospective cohort study included patients with gastric adenocarcinoma who underwent neoadjuvant chemotherapy followed by curative gastrectomy. Pretreatment clinicopathological variables, Becker tumor regression grade (TRG), and serum tumor markers were evaluated. Logistic regression was used to identify predictors of favorable pathological response, whereas Cox proportional hazards regression was performed to identify independent prognostic factors for disease-free survival (DFS). Sequential prognostic models were developed and internally validated using 1000 bootstrap resamples. A simplified postoperative clinicopathological risk classification based on pretreatment clinical N stage and Becker tumor regression grade was additionally developed to facilitate clinical interpretation and postoperative risk stratification. Results: A total of 109 patients were included. Favorable pathological response (Becker TRG1–2) was achieved in 68 patients (62.4%), whereas 41 patients (37.6%) had minimal or no pathological response (TRG3). In multivariable logistic regression analysis, pretreatment clinical T stage (cT4 vs. cT1–3) and clinical N stage (cN2–3 vs. cN0–1) were independently associated with a lower likelihood of achieving a favorable pathological response. For disease-free survival, pretreatment clinical N stage, Becker tumor regression grade, and log10-transformed CA19-9 remained independent prognostic factors in the multivariable Cox model. Sequential model development demonstrated progressive improvement in model discrimination, with the optimism-corrected Harrell’s C-index increasing from 0.697 for the clinical N stage model to 0.770 for the final model incorporating clinical N stage, Becker tumor regression grade, and CA19-9. Bootstrap internal validation demonstrated minimal optimism, and calibration analysis showed good agreement between predicted and observed disease-free survival. A simple postoperative clinicopathological risk classification successfully stratified patients into distinct prognostic groups. Conclusions: A clinicopathological prognostic model integrating pretreatment clinical N stage, Becker tumor regression grade, and serum CA19-9 demonstrated improved prognostic discrimination for disease-free survival compared with clinical N stage alone. The derived postoperative risk classification may provide a simple framework for postoperative risk stratification and could assist in individualizing postoperative surveillance. External validation is warranted before routine clinical implementation. Full article

Background: Head and neck cutaneous squamous cell carcinoma (HNcSCC) presents intersecting oncologic, functional, and reconstructive challenges. Although numerous clinicopathologic factors have been associated with recurrence, metastasis, and survival, their relationship with reconstructive complexity and patient-centered outcomes remains insufficiently studied. This review aimed to examine how established oncologic risk factors might inform reconstructive planning while distinguishing measured reconstructive evidence from hypothesis-generating clinical inferences. Methods: A structured PubMed/MEDLINE search conducted through 15 July 2026 was used to identify the literature addressing clinicopathologic prognostic factors in HNcSCC. Twenty-nine prognostic publications were retained for structured charting. Additional reconstructive, functional, aesthetic, and patient-reported outcome sources were identified through reference-list screening and were used solely for narrative contextualization. Because no dedicated multi-database systematic search of reconstructive outcomes was performed, the article is presented as a structured narrative review and hypothesis-generating research framework rather than a systematic review of reconstructive evidence. Results: The prognostic literature reported associations between adverse oncologic outcomes and factors including tumor size and depth, perineural invasion, lymphovascular invasion, poor differentiation, immunosuppression, recurrent disease, positive margins, nodal involvement, and extranodal extension. However, most of these studies did not measure post-excision defect characteristics, reconstructive technique, wound complications, functional recovery, scar quality, aesthetic outcomes, or patient-reported outcomes. Direct reconstructive evidence was limited and predominantly derived from site-specific, mixed-histology, technical, or methodological publications. Consequently, clinicopathologic factors should be regarded as potential upstream variables for future investigation rather than validated predictors of reconstructive outcomes. Conclusions: Current evidence supports oncologic risk stratification more strongly than prediction of reconstructive difficulty or patient-centered outcomes in HNcSCC. Prospective studies should jointly measure patient, tumor, treatment-field, defect, reconstructive, functional, aesthetic, and patient-reported variables. The proposed framework is intended to guide such research and is not a validated clinical prediction model. Full article

Background: Homeobox transcription factors regulate developmental programs, cellular plasticity, and tumor progression, yet the role of H2.0-like homeobox (HLX) in prostate cancer (PCa) remains poorly defined. We investigated the clinical significance of HLX and its relationship to the pro-metastatic transcription factor TBX2. Methods: Transcriptomic and clinical datasets from TCGA, MET500, and SU2C/PCF cohorts were analyzed to assess HLX expression, clinicopathologic associations, and its relationship with TBX2. Functional studies in human PCa cell lines included TBX2 gain- and loss-of-function, HLX knockdown, chromatin immunoprecipitation (ChIP), and expression analyses. Shared HLX- and TBX2-associated pathways were evaluated by Reactome enrichment analysis, and Hallmark Gene Set Enrichment Analysis compared castration-resistant prostate cancer (CRPC) bone metastases with high versus low HLX expression (GSE77930; n = 5/group). In vivo relevance was assessed in an orthotopic TBX2 dominant-negative PCa xenograft model. Results: Human PCa datasets showed that HLX expression was elevated in PCa versus normal prostate tissue and associated with higher Gleason grade, lymph node involvement, aggressive molecular subtypes, and shorter disease-free survival. HLX expression also positively correlated with TBX2 across human PCa cohorts. HLX- and TBX2-associated transcriptional programs converged on extracellular matrix organization, cell adhesion, NOTCH, and VEGF-MAPK signaling pathways. Furthermore, HLX-high CRPC bone metastases were enriched for epithelial–mesenchymal transition, NOTCH, TGF-β, inflammatory, angiogenic, hypoxic, and KRAS signaling pathways. Mechanistic studies showed that HLX knockdown suppressed extracellular matrix-associated genes and key NOTCH pathway components. ChIP demonstrated direct TBX2 binding to the HLX promoter, and genetic modulation of TBX2 expression established HLX as a downstream target of TBX2. Consistent with these findings, reduced HLX expression in orthotopic TBX2 dominant-negative xenografts was associated with loss of metastatic progression. Conclusions: HLX is a candidate biomarker of aggressive PCa and a direct transcriptional target of TBX2. These findings identify a previously unrecognized TBX2–HLX regulatory axis associated with metastatic transcriptional programs and aggressive disease in advanced PCa. Full article

Background: Patients with stage IIB–IIIB cutaneous melanoma remain at substantial risk of recurrence despite complete surgical resection. Accurate risk stratification is essential to optimize patient selection for adjuvant therapy and surveillance strategies. We aimed to evaluate the clinicopathological and molecular factors associated with recurrence in a real-world cohort of high-risk melanoma patients. Methods: We retrospectively analyzed 97 patients with stage IIB–IIIB cutaneous melanoma treated at a single tertiary referral center. Clinicopathological characteristics, molecular features, treatment-related variables, and sentinel lymph node (SLN) pathological characteristics were evaluated. Recurrence-free survival (RFS) was estimated using the Kaplan–Meier method. Independent prognostic factors were identified using multivariable Cox proportional hazards regression. Results: After a median follow-up of 88 months, 31 patients (32.0%) developed recurrence. Stage IIC showed the highest recurrence rate in the cohort (52.4%), compared with 25% in stage IIIA and 31.4% in stage IIIB. Consistently, in the multivariable analysis, compared with stage IIB, only stage IIC remained independently associated with worse recurrence-free survival (hazard ratio [HR] = 3.57, 95% confidence interval [CI]: 1.08–11.82; p = 0.037), whereas neither stage IIIA nor stage IIIB differed significantly from stage IIB. Female sex was independently associated with a lower risk of recurrence (HR 0.33, 95% CI 0.14–0.79; p = 0.012). Although BRAF V600E-mutated tumors showed higher recurrence rates and shorter recurrence-free survival in univariable analyses, BRAF V600E status was not independently associated with recurrence in the multivariable model (p = 0.250). Higher lymphoid infiltration density was associated with improved RFS in univariable analysis, although this finding was limited by substantial missing data and non-standardized pathological assessment. Conclusions: In this exploratory retrospective analysis, female sex and stage IIC were independently associated with RFS. These findings should be interpreted cautiously given the small sample size, limited number of recurrence events, and incomplete availability of some clinicopathological and molecular variables. The prognostic associations observed for BRAF V600E status and lymphoid infiltration, as well as the analyses according to adjuvant treatment, should be considered exploratory and hypothesis-generating. The unfavorable outcomes observed in stage IIC disease support growing evidence that this subgroup represents a biologically aggressive form of melanoma despite the absence of regional nodal involvement. Our findings do not challenge the validity of the AJCC staging system but suggest that clinically relevant heterogeneity may exist within established AJCC stage groups. Full article

Background/Objectives: Under the current molecular classification of endometrial cancer, the p53-abnormal group is defined as having the worst prognosis, but the clinicopathological position of low-grade endometrial cancer with p53-abnormal expression relative to high-grade endometrial cancer remains unclear. We previously showed that low-grade endometrial cancer with p53-abnormal expression more closely resembles low-grade endometrial cancer with p53 wild-type expression than high-grade endometrial cancer and that the ERBB2 gene, encoding Human Epidermal Growth Factor Receptor 2 (HER2) protein, is more highly expressed in high-grade endometrial cancer. This study compared HER2 immunohistochemical expression (IHC) among low-grade endometrial cancer with wild-type p53 expression (EC^lop53^wt), low-grade endometrial cancer with p53-abnormal expression (EC^lop53^ab), and high-grade endometrial cancer (EC^hi), in order to characterize EC^lop53^ab. Methods: We retrospectively analyzed 70 endometrial cancer cases treated at Kyushu University Hospital in 1992–2022. Tumors were classified as EC^lop53^wt, EC^lop53^ab, and EC^hi based on histopathology and p53 immunohistochemistry, with EC^hi corresponding to conventional uterine serous carcinoma. HER2 expression was evaluated immunohistochemically using a standardized scoring system (0, 1+, 2+, 3+), and its distribution was compared across the three groups, together with clinicopathological parameters and patient outcomes. Results: EC^hi showed the highest frequency and intensity of HER2 expression, with a substantially larger proportion of HER2 IHC 3+ cases than EC^lop53^wt and EC^lop53^ab (p < 0.0001 and p = 0.0146, respectively). Meanwhile, there was no significant association between EC^lop53^wt and EC^lop53^ab (p = 0.3794). In addition, HER2 IHC 3+ had significant associations with older age (≥60 years) and substantial lymphovascular space invasion (p = 0.0003 and 0.0174, respectively). Conclusions: EC^lop53^ab exhibits HER2 profiles and clinical behavior more similar to EC^lop53^wt, supporting the more nuanced application of molecular classification and HER2-targeted therapy in endometrial cancer. Full article

Bacterial vaginosis (BV) and aerobic vaginitis (AV) are usually described as distinct forms of vaginal dysbiosis. BV is characterized by depletion of lactobacilli, overgrowth of anaerobic microorganisms, and biofilm formation, whereas AV is associated with inflammatory changes, epithelial disruption, and predominance of aerobic bacteria. Over the past two decades, this distinction has profoundly influenced the understanding, diagnosis, and management of vaginal disorders. Despite their apparent differences, the relationship between BV and AV remains incompletely understood. Growing evidence indicates that many women exhibit microbiological and microscopic patterns that cannot be readily classified within existing diagnostic frameworks. Intermediate Nugent scores, mixed vaginitis, transitional ecological states, post-treatment microbiota reconstitution, physiological hypoestrogenic conditions, and uncommon inflammatory patterns all challenge the traditional view of BV and AV as strictly separate entities. This narrative review examines the historical evolution of BV and AV concepts, compares their microbiological, immunological, and epithelial characteristics, and evaluates the diagnostic paradigms currently used to identify vaginal dysbiosis. The strengths and limitations of clinical and diagnostic approaches are discussed together with the extent to which contemporary international guidelines reflect current biological knowledge. Particular emphasis is placed on intermediate, mixed, and overlapping states that blur the boundaries between established diagnostic categories. The available evidence supports the clinical usefulness of distinguishing BV and AV as separate clinicopathological entities. However, it also indicates that vaginal ecosystem disturbances frequently extend beyond rigid dichotomous classifications. Current diagnostic categories remain valuable tools for clinical practice, yet they may only partially capture the complexity and dynamic nature of vaginal dysbiosis. Understanding how microbial communities, host responses, epithelial integrity, and physiological factors interact remains a major challenge for future research and clinical interpretation. Full article

Integrins are heterodimeric transmembrane receptors that mediate bidirectional signaling and regulate cell–cell and cell–extracellular matrix interactions. Integrin αvβ6 is an epithelial-associated integrin that has emerged as a promising molecular target for PET/CT imaging using integrin αvβ6-directed radiotracers such as ⁶⁸Ga-Trivehexin, and, most recently, for antibody–drug conjugate therapy in epithelial malignancies. Unexpected physiological and incidental uptake within the pituitary gland has been reported in integrin αvβ6-targeted PET studies, including uptake in morphologically normal pituitary glands and pituitary neuroendocrine tumors (PitNETs). However, the histological basis of integrin αvβ6 expression in the human pituitary gland remains poorly understood. The aim of this study is to characterize the immunohistochemical expression of integrin αvβ6 in normal human pituitary tissue and PitNETs and to evaluate its potential implications for integrin αvβ6-targeted imaging and theranostic applications. Five complete adult pituitary glands obtained at autopsy and 28 PitNETs were examined by immunohistochemistry for integrin αvβ6. Staining distribution, intensity, and cellular localization were assessed in the adenohypophysis, neurohypophysis, and Rathke’s cleft remnants. PitNETs were classified according to transcription factor expression (PIT1, TPIT, and SF1). Among the 28 PitNETs, 17 were SF1-lineage (60.7%), three were PIT1-lineage (10.7), two were TPIT-lineage (7.1%), three lacked a dominant transcription factor (10.7%), and three showed plurilineage expression (10.7%). Integrin αvβ6 expression was evaluated semiquantitatively according to staining intensity and the percentage of positive tumor cells. In normal pituitary glands, integrin αvβ6 immunoreactivity was predominantly membranous and localized to larger adenohypophyseal cells irrespective of transcription factor lineage or hormone phenotype. Strong expression was also observed in the epithelial lining cells of Rathke’s cleft remnants, whereas the neurohypophysis lacked detectable integrin αvβ6 expression. Among the 28 PitNETs, integrin αvβ6 expression was detected in 20 cases (71.4%). Positive tumors demonstrated variable staining intensity and extent, ranging from 20% to 100% positive tumor cells. By lineage, integrin αvβ6 expression was detected in 13 of 17 SF1-lineage tumors (76.5%), one of three PIT1-lineage tumors (33.3%), and zero of two TPIT-lineage tumors (0%). Additionally, all three tumors lacking a dominant transcription factor (100%) and all three plurilineage tumors (100%) demonstrated integrin αvβ6 expression. Eleven integrin αvβ6-positive tumors showed expression in ≥50% of tumor cells, and six exhibited strong or diffuse immunoreactivity. Integrin αvβ6 expression in adenohypophyseal cells and Rathke’s cleft remnants provides a histological explanation for physiological pituitary uptake observed on αvβ6-targeted PET/CT imaging. The high prevalence of integrin αvβ6 expression in PitNETs, particularly in a subset demonstrating strong and diffuse immunoreactivity, suggests potential applicability of integrin αvβ6-targeted molecular imaging and theranostic approaches, including both radioligand- and antibody-based strategies. However, these applications remain investigational and require further validation in preclinical and clinical studies. At the same time, physiological integrin αvβ6 expression in normal anterior pituitary tissue may limit imaging specificity and should be considered when developing integrin αvβ6-targeted radioligand therapies. Further clinicopathological and imaging correlation studies are warranted to define the diagnostic and therapeutic role of integrin αvβ6-targeted approaches in PitNETs. Full article

Background/Objectives: The prognostic significance of young age in breast cancer (BC) remains controversial, with varying findings across studies. This study aimed to evaluate the imaging characteristics, pathological features, and survival outcomes of BC in young patients aged ≤ 35 years by dividing them into two groups and to compare outcomes between these subgroups to determine whether very young age alone is associated with worse prognosis. Methods: This retrospective study included patients aged ≤ 35 years with malignant breast lesions who underwent image-guided interventions at a single center between January 2011 and December 2024. Patients were divided into two groups: Group 1 (≤30 years) and Group 2 (31–35 years). Demographic, imaging, and pathological data, as well as survival outcomes, were analyzed. Results: A total of 34 patients (Group 1: n = 14, Group 2: n = 20) with malignant breast lesions underwent 40 image-guided procedures. No significant differences were observed between groups in imaging features, pathological characteristics, or pTNM stage distribution. Median follow-up was 68 months. One-year overall survival (OS) was 100% in both cohorts; 5-year OS rates were 100% and 92.3%, respectively, with no statistically significant difference (p = 0.784). Median event-free survival (EFS) was 60.5 months, also without a significant difference between groups (p = 0.897). None of the clinicopathological factors assessed were significantly associated with OS in this exploratory analysis. Conclusions: In women ≤ 35 years, tumor characteristics and patient outcomes were similar between those aged ≤ 30 and 31–35 years. OS and EFS were favorable in both groups, indicating that within the ≤35-year population studied, being ≤30 years old was not associated with worse outcomes than being 31–35 years old. Although advanced stage disease was more frequently observed in the younger group, this difference was not statistically significant. Full article

Background: The role of primary tumor resection (PTR) in patients with de novo stage IV colorectal cancer remains controversial, particularly in the context of patient selection and tumor biology. This study aimed to evaluate the association between PTR and survival outcomes and to identify clinical, molecular, and inflammatory-nutritional prognostic factors in patients with de novo stage IV colorectal cancer. Methods: Medical records of 204 patients with de novo stage IV colorectal adenocarcinoma treated at Ankara Etlik City Hospital from December 2022 to December 2025 were reviewed retrospectively. Patients were grouped according to PTR status. Baseline clinicopathological features, molecular tumor profile, metastatic disease extent, treatment characteristics, and inflammatory-nutritional markers were recorded. Survival outcomes were assessed in terms of progression-free survival (PFS) and overall survival (OS) using the Kaplan–Meier method and Cox proportional hazards regression models, as well as 1:1 propensity score matching and sensitivity analyses. Results: PTR was performed in 114 patients (55.9%), while 90 patients (44.1%) did not undergo PTR. Patients who underwent PTR were younger, had better Eastern Cooperative Oncology Group (ECOG) performance status, and more frequently had single-organ metastatic disease. In the unmatched cohort, patients who underwent PTR had longer median PFS and OS than those without PTR (15.88 vs. 11.03 months and 16.14 vs. 11.54 months, respectively; both log-rank p < 0.001). In the adjusted Cox models, PTR corresponded to lower risks of progression (hazard ratio [HR]: 0.50; 95% confidence interval [CI]: 0.34–0.74; p < 0.001) and death (HR: 0.48; 95% CI: 0.30–0.77; p = 0.002), whereas BRAF mutation showed higher risks of progression (HR: 3.00; 95% CI: 1.70–5.29; p < 0.001) and death (HR: 3.42; 95% CI: 1.83–6.38; p < 0.001). In the propensity score–matched cohort comprising 50 matched pairs, PTR remained associated with a lower risk of progression or death (HR: 0.59; 95% CI: 0.40–0.87; p = 0.007), whereas its association with OS was not statistically significant (HR: 0.69; 95% CI: 0.42–1.13; p = 0.141). Sensitivity analyses generally yielded estimates favoring PTR, although the statistical significance of the association with OS varied across analyses. Patients with higher prognostic nutritional index (PNI) values showed more favorable survival outcomes. Conclusions: In this retrospective cohort, PTR was consistently associated with longer PFS, whereas its association with OS was less robust across the adjusted analyses. Because these patients had a more favorable baseline profile, these associations should be viewed with caution and in relation to patient selection. BRAF mutation and PNI emerged as important prognostic factors, supporting a multidimensional approach to survival assessment that incorporates metastatic disease burden, tumor biology, and inflammatory-nutritional status. Full article

Background/Objectives: Cutaneous squamous cell carcinoma (cSCC) is the second most common non-melanoma skin cancer (NMSC) and represents the leading cause of NMSC-related deaths. Despite its growing global burden, comprehensive epidemiological and clinicopathological data from Easter Europe remains limited. This study aimed to evaluate the epidemiological, clinical, histopathological, and surgical characteristics of cSCC diagnosed before, during and after the COVID-19 pandemic. Methods: We conducted a retrospective, descriptive observational study including 332 lesions diagnosed between January 2017 and December 2025 at the Clinical Pathology Department of the Mureș Clinical County Hospital. Demographic, epidemiological, topographic, histopathologic, surgical, and volumetric parameters were analyzed. Tumours were stratified into low-, high-, and very-high-risk categories according to the National Comprehensive Cancer Network (NCCN) criteria. Results: The cohort demonstrated a significant male predominance (n = 193 vs. n = 139; p = 0.0355), with females presenting a higher median age (77 vs. 75; p = 0.0489). Lesions were predominantly located in the head and neck region (n = 216; p < 0.0001), which was significantly associated with very-high-risk tumours (p = 0.0051). Low-risk tumours accounted for 62.35% of cases, while high-risk and very-high-risk lesions comprised 19.88% and 17.77%, respectively (p < 0.0001). Ulcerations were strongly associated with very-high-risk tumours (p < 0.0001). Poor differentiation was more frequent outside the head and neck region (p < 0.0001) and varied significantly across the pandemic periods (p = 0.0349). Tumoral and excision volumes were higher in very-high-risk (p = 0.0070; p = 0.0004) and ulcerated tumours (p < 0.001), with a peak in volume during the COVID-19 period (p < 0.0001). A decrease through the years of diagnosis was observed in tumoral volumes (r = −0.2295; p < 0.0001) and patients showed a weak positive correlation with diagnosis year (r = +0.13; p = 0.019). Conclusions: The study provides an epidemiological and clinicopathological characterization of cSCC within one of the largest Romanian cohorts to date. Tumour aggressiveness was primarily driven by histopathological and topographical features rather than demographic factors. While the COVID-19 pandemic did not induce persistent changes in tumour risk profiles or surgical outcomes, it influenced diagnosis timing and tumour burden. These findings highlight the importance of incorporating temporal and emerging systemic factors, such as pandemics, and infectious events, into future epidemiological models to improve preparedness, early detection, future treatment schemes, and risk stratification in cSCC. Full article

Background: Cellular senescence exerts a complex influence on BRCA progression and TME remodeling. However, the specific roles of ASIGs in regulating the TME and determining patient outcomes remain unclear. Methods: Using TCGA (training), METABRIC (validation), and single-cell RNA-seq datasets, we systematically characterized ASIGs in BRCA. Prognostic ASIGs were identified to define molecular subtypes and construct a 17-gene LASSO-Cox risk model, which was integrated with clinical factors to develop a prognostic nomogram. Microenvironmental features and cell–cell communication networks were deconstructed using computational deconvolution and single-cell algorithms (SCISSOR and CellChat). Results: We established a robust 17-gene ASIG-based prognostic signature that effectively stratified BRCA patients into high- and low-risk groups and served as an independent prognostic predictor (HR = 3.94, p < 0.001). The nomogram accurately predicted 1-, 3-, and 5-year overall survival. Notably, the two risk groups exhibited strikingly distinct TME landscapes. The low-risk group was characterized by a coordinated, B cell-centric immune network, whereas the high-risk group displayed T cell exhaustion and immunosuppressive myeloid infiltration. Conclusions: The ASIG-based prognostic risk model is independent of traditional clinicopathological factors, providing a robust tool for patient risk stratification and offering biological insights into senescence-driven microenvironmental remodeling. Full article

Equine piroplasmosis, caused by the intraerythrocytic protozoan Theileria equi, is a globally distributed tick-borne disease characterized by persistent infection and variable clinical manifestations. Although oxidative stress has been implicated in the pathogenesis of several hemoprotozoan diseases, information regarding redox imbalance and its relationship with inflammatory responses in horses naturally infected with T. equi remains limited. This study aimed to evaluate oxidative stress, antioxidant status, inflammatory cytokines, and clinicopathological alterations in horses naturally infected with T. equi. Thirty-five horses naturally infected with T. equi and twenty clinically healthy horses were enrolled. Infection was confirmed by clinical evaluation, hematological and biochemical analyses, an indirect fluorescent antibody test, and polymerase chain reaction. Serum concentrations of interferon-gamma, tumor necrosis factor-alpha, reduced glutathione, and malondialdehyde were assayed. Infected horses showed significantly lower platelet counts and significantly higher serum activities of aspartate aminotransferase than controls. Serum interferon-gamma and tumor necrosis factor concentrations were significantly increased, indicating persistent inflammatory activation. Infected horses also exhibited significantly higher malondialdehyde concentrations and lower reduced glutathione levels, consistent with enhanced lipid peroxidation and impaired antioxidant defenses. Correlation analyses revealed a negative association between reduced glutathione and white blood cell count and between malondialdehyde and red blood cell count, whereas malondialdehyde concentrations were positively associated with clinical score. Chronic T. equi infection is associated with oxidative stress, depletion of antioxidant defenses, and sustained inflammatory responses. The interaction between oxidative stress and inflammation may contribute to hematological abnormalities and disease expression. Full article

Purpose: This study aimed to determine the optimal temporal threshold for distinguishing “early” from “late” liver metastasis in patients who developed liver metastasis after colorectal cancer (CRC) surgery, and to evaluate whether KRAS and BRAF^V600E mutations, along with other clinicopathological factors, are associated with the timing of liver metastasis. Methods: This retrospective study utilized clinical and pathological data from patients who developed liver metastasis after radical CRC surgery at two centers from 2019 to 2023. X-tile software was used to identify the optimal temporal threshold. Logistic regression analysis was applied to determine if KRAS/BRAF^V600E mutations and other potential factors are independently associated with the time to onset of liver metastasis. Results: X-tile analysis identified 11 months post-surgery as the optimal cutoff for distinguishing early metachronous liver metastasis (EMLM) from late metachronous liver metastasis (LMLM), classifying 114 cases into the EMLM group and 72 into the LMLM group. Comparative analysis indicated statistically significant differences between the two groups in lymphovascular tumor emboli, perineural invasion, and postoperative adjuvant therapy (p < 0.05). Logistic regression analysis revealed that neither KRAS mutation (OR, 1.185; 95% CI: 0.641–2.190; p = 0.587) nor BRAF^V600E mutation (OR, 2.836; 95% CI: 0.302–26.642; p = 0.363) was independently associated with the timing of liver metastasis. In contrast, postoperative adjuvant therapy showed a statistical association with a likelihood of LMLM (OR, 0.253; 95% CI: 0.105–0.611; p = 0.002). Conclusions: This study identified 11 months post-CRC surgery as the optimal cutoff for differentiating EMLM versus LMLM. In this cohort, no statistically significant association was observed between KRAS/BRAF^V600E mutations and the timing of liver metastasis, whereas postoperative adjuvant therapy was statistically correlated with the likelihood of LMLM. This stratification may guide personalized surveillance strategies and provide valuable insights for future mechanistic investigations into the temporal heterogeneity of post-surgical liver metastasis. However, the interpretation and generalization of the findings require external validation in prospective cohorts. Full article