Early-onset colorectal cancer (EOCRC), defined as diagnosis before 50 years of age, has increased in incidence globally, but its clinicopathologic profile and prognostic significance remain incompletely characterized, particularly in Southeast Asian populations with limited access to organized screening.

To compare clinicopathologic characteristics and survival outcomes between EOCRC and late-onset colorectal cancer (LOCRC) following curative resection, and to identify independent prognostic determinants in a regional Vietnamese surgical cohort.

This retrospective cohort study included 486 patients with stage I-III colorectal adenocarcinoma who underwent curative laparoscopic resection at a tertiary center in the Mekong Delta between 2016 and 2022.

EOCRC (184 patients, 37.9%) was associated with higher rates of poor differentiation, mucinous or signet-ring cell histology, lymphovascular invasion, and perineural invasion compared with LOCRC (all p<0.05). Overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) did not differ significantly between groups. In the overall cohort (log-rank p=0.72, 0.15, and 0.96, respectively). On multivariable analysis, postoperative complications were the dominant independent prognostic factor for OS (hazard ratio [HZ] 8.28; 95% confidence interval [CI] 4.87-14.09) and RFS (HZ 4.81; 95%CI 3.03-7.65), whereas age at onset was not independently associated with either outcome. Stage-stratified curves suggested a less favorable survival pattern among patients with stage III EOCRC, particularly for CSS and RFS.

Despite a more aggressive histopathologic profile, EOCRC showed comparable survival to LOCRC in the overall cohort. Stage-stratified curves suggested a less favorable survival pattern among patients with stage III EOCRC, while postoperative complications represented the dominant modifiable determinant of outcome.

Gastric adenocarcinoma remains one of the leading causes of cancer mortality worldwide, according to the International Agency for Research on Cancer. Stage III, as defined by the 8th edition of the American Joint Committee on Cancer Tumor, Node, and Metastasis (TNM) system, comprises a biologically heterogeneous group, resulting in clinicopathological variations that directly impact prognosis and therapeutic decisions.

To evaluate the clinicopathological features, surgical morbidity and mortality, and overall survival of patients with gastric adenocarcinoma treated at a tertiary center, and to analyze prognostic differences among stage III subgroups.

This retrospective cohort study included patients treated between 2008 and 2018. Demographic variables, tumor characteristics, TNM staging (8th edition), type of surgical procedure, complications according to the Clavien-Dindo classification, and 30-day mortality were analyzed. Overall survival was estimated using the Kaplan-Meier method and compared with the log-rank test, with a significance level of 5%.

This retrospective cohort study included patients treated between 2008 and 2018. We analyzed demographic variables, tumor characteristics, TNM staging (8th edition), type of surgical procedure, complications according to the Clavien-Dindo classification, and 30-day mortality. Overall survival was estimated using the Kaplan-Meier method and compared with the log-rank test, with a significance level of 5%.

Stage III gastric adenocarcinoma demonstrates marked clinicopathological heterogeneity, which directly impacts morbidity, mortality, and survival. Lymph node involvement is a relevant prognostic determinant.

Pancreatic neuroendocrine tumors (pNETS) constitute a heterogeneous and rare disease worldwide. Diagnosis rates have been increasing, and the evaluation of prognostic factors has become even more important in the treatment decision-making process.

To present results and prognostic factors in patients undergoing surgical treatment for pNETS at a single Brazilian center.

The most frequently performed surgical procedure was PCC+S 60.0%. The median hospital stay was 8 (5-13) days, and postoperative mortality occurred in 1.7%. Overall survival in 3 and 5 years was 93.8 and 92.1%, respectively. Disease-free survival at 3 and 5 years was 87.1 and 71.8%, respectively. Patients with tumors smaller than 2.0 cm did not present with lymph node disease or recurrence, and patients with tumors measuring 2.1-2.5cm had lymph node disease in 11.1% and recurrence in 11.1%. In univariate and multivariate analysis, the presence of lymphatic and perineural invasion and Ki67 (3-20) were strongly correlated with positive lymph node disease and recurrence, respectively.

The presence of lymphatic and perineural invasion, Ki67 (3 to 20), and tumors larger than 2.5 cm correlated with positive lymph node disease and recurrence.

Childhood kidney cancer is one of the most common pediatric malignancies without comprehensive assessments of its global burden. We aimed to quantify the global burden from 1990 to 2021 and project trends to 2050.

Data on incidence, mortality, and disability-adjusted life years (DALYs) for childhood kidney cancer were obtained from the Global Burden of Disease (GBD) 2021. Temporal trends were analyzed using Joinpoint regression. Spearman's rank correlation was used to evaluate the association between disease burden and the sociodemographic index (SDI). Future burden trends were predicted with a Bayesian age-period-cohort (BAPC) model.

In 2021, there were 9576 global incident cases of childhood kidney cancer, resulting in 3,063 deaths and 268,049 DALYs. From 1990 to 2021, global burden of childhood kidney cancer declined overall. However, substantial disparities persisted across regions and SDI levels. Low-SDI regions experienced disproportionately poorer prognosis, while children under five years and boys bore the greatest burden. Projections indicate continued declines in global burden through 2050.

Despite overall declines in the global burden of childhood kidney cancer, substantial disparities persist across sociodemographic contexts. These findings emphasize the importance of improving early diagnosis, access to standardized treatment, and delivery of pediatric oncology care in high-burden settings.

IntroductionGiant cell tumour of bone is a benign but locally aggressive condition associated with a risk of recurrence and functional impairment. This study aimed to evaluate the clinical presentation, functional outcomes, and oncological outcomes of patients with giant cell tumour of bone treated at a tertiary orthopaedic oncology centre, with particular emphasis on local recurrence, pulmonary metastasis, surgical management, and survival.MethodsA single-centre retrospective cohort study was conducted involving 151 patients with histologically confirmed giant cell tumour of bone treated between 2006 and 2023. Demographic characteristics, tumour location, treatment modality, recurrence, metastasis, and survival outcomes were analysed. Functional outcomes were assessed using the Musculoskeletal Tumour Society (MSTS) score and the Toronto Extremity Salvage Score (TESS) in a subset of 114 patients (75.5%). Time-to-event outcomes, including local recurrence-free survival, were analysed using Kaplan-Meier methods. The mean duration of follow-up was 81.7 ± 63.8 months.ResultsLocal recurrence occurred in 17 patients (11.3%), with a 5-year local recurrence-free survival rate of 88.1%. Pulmonary metastasis was observed in 5 patients (3.3%). Among the 114 patients with available clinical and functional data, intralesional curettage was associated with significantly higher functional scores than wide resection (MSTS: 87.4 ± 8.1 vs 70.9 ± 14.3, p < 0.001; TESS: 89.9 ± 6.8 vs 80.1 ± 11.2, p < 0.001) for tumours in the lower limb. No significant functional differences were observed between surgical approaches in the upper limb. The five-year overall survival rate was 94.7%. Five-year disease-free survival and event-free survival rates were 87.7% and 82.7%, respectively. Median survival outcomes were not reached.ConclusionGiant cell tumour of bone demonstrates excellent long-term survival, with local recurrence representing the primary oncological challenge. Intralesional curettage provides superior functional outcomes for selected lower-limb tumours, while wide resection remains essential for aggressive or recurrent disease.

Abdominal compression (AC) using a belt-based system is widely employed in radiation therapy to limit respiration-induced target motion for abdominal and hepatic malignancies. While AC has demonstrated efficacy in reducing intrafraction motion amplitude, the interfractional anatomical consequences of daily compression belt (CB) placement variability remain poorly characterized. A clearer understanding of this variability is necessary to determine whether online adaptive radiotherapy (oART) is required to maintain dosimetric robustness throughout the treatment course.

This study aims to quantify interfractional anatomical variability associated with CB use in a clinical MR-guided radiotherapy cohort and to compare these findings against a matched cohort of non-compressed abdominal patients to determine the clinical significance of CB-induced setup variability.

Daily treatment MR images were retrospectively collected from 17 CB patients and 17 matched non-CB controls treated on an MR-Linac. External contours were delineated at the center of the planning target volume (PTV) and at the region of maximum compression for CB patients. Interfractional variability was assessed using cross-sectional area (CSA), Dice Similarity Coefficient (DSC), Mean Distance to Agreement (MDA), and Hausdorff Distance (HD). Interfractional organ displacement of the liver and kidneys was quantified via rigid registration. Linear mixed-effects models (LMEMs) evaluated the association between patient demographics-including age, BMI, sex, subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT)-and interfractional variability metrics.

Interfractional DSC over the PTV region was significantly lower in the CB cohort compared with non-CB controls (p = 0.01 and p = 0.03 for comparisons to fraction one and sequential fraction comparisons, respectively), and MDA was significantly elevated in the CB cohort (p < 0.001). No significant difference in CSA variability was observed between cohorts. In the maximum compression region, median HD was 1.6 cm relative to fraction one, with no significant correlation between compression-region and PTV-region CSA variability (p = 0.99). Older age, male sex, and higher BMI were associated with improved belt-contact shape reproducibility (all p < 0.05), though these demographic effects did not translate to PTV-region stability. LMEM analysis revealed that fixed demographic effects explained only a small fraction of PTV variability (R² _m = 0.06-0.29), with the remainder attributable to patient-specific random effects. Interfractional organ displacement ranged from 5.91 to 9.15 mm across organs and cohorts, with no statistically significant difference between groups.

CB use introduces measurable but modest increases in interfractional anatomical variability at the PTV level compared with standard abdominal setups. Compression-site variability does not propagate directly to the treatment target, and patient demographics alone are insufficient to predict CB-induced setup variability. Daily MR-based image guidance and selective adaptive replanning remain the appropriate management strategy for patients treated with abdominal compression.

We aimed to evaluate temporal changes in the diagnostic performance of thyroid fine-needle aspiration biopsy (FNAB) over a 15-year period in a single-center, surgically confirmed cohort.

We retrospectively analyzed thyroid FNABs performed between 2009 and 2023, dividing the data into two intervals (Group 1: 2009-2014; Group 2: 2015-2023). All specimens were interpreted by the same two experienced cytopathologists. Sensitivity, specificity, and Youden's J were calculated at four diagnostic thresholds (≥AUS/FLUS, ≥FN/SFN, ≥SM, and malignant only), and level-specific likelihood ratios (LRs) were compared between cohorts. Overall diagnostic discrimination was assessed with receiver operating characteristic (ROC) curves and compared by DeLong's test.

The study included 1,241 nodules; after excluding non-diagnostic cytology, 601 nodules in Group 1 and 553 in Group 2 were available for diagnostic performance analysis. At the ≥AUS/FLUS cutoff, sensitivity increased from 85.6% to 94.8%, while specificity declined from 58.4% to 33.0% (both p<0.01). Specificity at higher thresholds remained similar or increased in Group 2. The area under the ROC curve (AUC) was 0.799 for Group 1 and 0.831 for Group 2 (p = 0.24). Of the five Bethesda LRs, only that for AUS/FLUS changed significantly (1.24 vs. 0.37; p<0.01).

The overall discriminative ability of the Bethesda System remained stable over 15 years. The decrease in the AUS/FLUS LR reflects a spectrum effect driven by more selective surgical referral patterns and should be interpreted as a change in cohort composition rather than diminished test performance.

Thyroid nodules diagnosed as atypia of undetermined significance (AUS) are one of the most challenging categories in thyroid cytopathology due to histopathological ambiguity and complexities in clinical management. Therefore, this study aimed to develop and evaluate the diagnostic accuracy of a novel malignancy risk scoring system integrating cytological subclassification and key ultrasonographic features.

A retrospective analysis was conducted on 357 patients who underwent thyroidectomy following an AUS cytology diagnosis. Cytological samples were subclassified as AUS-N or AUS-O, based on the presence of nuclear atypia, and fundamental sonographic parameters were recorded. Independent predictors of malignancy were identified using multivariable logistic regression, and the AUS-malignancy risk score (AUS-MRS) was developed accordingly. Diagnostic performance was compared with existing classification systems: ACR-TIRADS, EU-TIRADS, and K-TIRADS.

The AUS-MRS demonstrated the highest diagnostic performance, with a sensitivity of 84.6%, specificity of 79.6%, and a diagnostic odds ratio (DOR) of 21.8. Among the conventional systems, ACR-TIRADS showed the highest sensitivity (89.1%) but had lower specificity (69.7%) and a DOR of 18.4. EU-TIRADS and K-TIRADS showed more balanced metrics, with sensitivities of 82.7% and 81.4%, specificities of 73.6% and 74.1%, and DORs of 18.2 and 16.7, respectively. The inclusion of nuclear atypia increased specificity across TIRADS models (>85%); however, this was accompanied by reduced sensitivity and did not yield substantial gains in diagnostic performance.

The AUS-MRS may offer improved diagnostic utility compared to existing ultrasound-based classification systems for assessing malignancy risk in AUS nodules.

Lung adenocarcinoma (LUAD) is the most common form of lung cancer. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is abnormally expressed in various tumor tissues and is associated with malignant phenotypes. However, the clinical significance, function, and mechanism of LUAD invasion and metastasis remain unclear.

We retrospectively enrolled 100 patients with LUAD in this study. Initially, qRT-PCR was performed to detect PCSK9 levels in clinical tissues. Subsequently, bioinformatics analysis of scRNA-seq and The Cancer Genome Atlas Program (TCGA) datasets was performed to predict the role of PCSK9 in tumor cell malignancy and its potential downstream pathways. These predictions were validated experimentally using the CCK-8 assay, TUNEL staining, wound healing, transwell invasion assay, and an in vivo lung metastasis model. Finally, Western blotting and an AKT inhibitor (MK2206) were used to verify the underlying mechanism.

PCSK9 was significantly upregulated in LUAD tissues compared to paracancerous tissues and was associated with poorer OS and DFS. Bioinformatics analysis of scRNA-seq data and TCGA analysis predicted that PCSK9 is highly enriched in tumor cells and is involved in EMT, and that the PI3K/AKT pathway plays a significant role in LUAD development. Experiments confirmed that PCSK9 markedly promoted LUAD cell proliferation, migration, and invasion in vitro and lung metastasis in vivo. PCSK9 overexpression significantly upregulated p-AKT, p-PI3K, and p-mTOR levels. Furthermore, the AKT inhibitor, MK2206, reversed the promoting effects of PCSK9.

PCSK9 expression is associated with the prognosis and diagnosis of LUAD. This molecule activates the PI3K/AKT signaling pathway, thereby driving invasion, metastasis, and proliferation in LUAD.

Aging is one of the strongest risk factors for cancer, and its impact is particularly evident in malignancies of the reproductive system. Ovarian, endometrial, cervical, vulvar, prostate, and penile cancers are mainly diagnosed in older adults and often show different clinical and biological features compared with the same tumors in younger patients. Aging is associated with hormonal changes, immune decline, epigenetic alterations, and accumulation of DNA damage, all of which contribute to cancer development and progression. At the same time, many older patients have frailty and multiple comorbidities, which can limit the use of screening programs and invasive diagnostic procedures. This often leads to delayed diagnosis and worse outcomes. Cell-free DNA (cfDNA) is a minimally invasive biomarker that can be obtained from blood samples and provides molecular information on both tumor and host tissues. Circulating DNA reflects tumor-specific alterations but is also influenced by aging-related changes in DNA release, fragmentation, and methylation. For this reason, aging must be considered when cfDNA-based biomarkers are applied in clinical practice. In this review, we describe how aging influences the biology of reproductive system cancers and how these processes are mirrored in cfDNA profiles. We focus on the clinical use of cfDNA for cancer detection and monitoring in older and fragile patients. Special attention is given to repetitive elements in cfDNA, which are strongly affected by aging and tumor-related epigenetic changes and can be detected with high sensitivity even when the tumor fraction is low. We propose an integrative mechanistic framework in which age-related epigenetic and genomic changes influence both tumor biology and cfDNA composition, with transposable elements acting as a central link between aging and cancer.