Large prospective studies in high-income countries have enabled the estimation of preventable cancer cases, guiding cancer control strategies. With breast cancer incidence rising rapidly in Malaysia, there is an urgent need for locally relevant data to inform effective prevention and control measures. We quantified the population-level contribution of risk factors in Malaysia using population-specific prevalence and literature-based relative risks.

We calculated population attributable risk using: (1) Malaysia-specific prevalence from national surveys and local epidemiological studies and (2) relative risks derived from meta-analyses of Asian prospective cohorts or case-control studies. We estimated attributable proportions using Levin's formula, adjusted for the joint effects of risk factors with a multiplicative model, and generated simulation-based confidence intervals to quantify their impact on overall disease burden.

Mammographic density (MD) accounted for 32.8% of breast cancer burden in Malaysian women, followed by modifiable risk factors-elevated body mass index (BMI, 14.7%) and passive smoking (8%). Family history and genetic factors collectively contributed 12.1%. Reproductive factors play a pronounced role before menopause, whereas BMI predominate after menopause. Their impact varies across ethnic groups: MD was most influential among Chinese women, while elevated BMI played a greater role among Malays and Indians.

A notable proportion of the breast cancer burden in Malaysia may be attributable to lifestyle and reproductive factors, while genetic susceptibility and MD also contribute importantly to disease burden. These findings support a balanced approach to breast cancer control, combining targeted prevention with risk-based early detection tailored to age and ethnic differences.

Purpose To compare artificial intelligence-based breast cancer detection and short-term breast cancer risk prediction models in their intended and nonintended settings over a single mammography screening round. Materials and Methods In this retrospective study, the Cohort of Screen-Age Women-Case Control dataset from Sweden (May 2008-December 2016; Hologic) was used, including patients with screen-detected and interval cancers, with interval cancers defined as a diagnosis more than 60 days after screening. Two examination-based settings were evaluated: detection (screening examinations) and short-term risk (screen-negative examinations). Mirai Risk, RSNA Detection (2023 challenge winner), Transpara Detection, and Transpara Risk models were assessed in both intended and nonintended settings. Discriminative performance was evaluated using the area under the receiver operating characteristic curve (AUC), and then clinically relevant sensitivity and specificity thresholds were compared. Results A total of 20 187 examinations (7430 women) were included, with 741 examinations leading to diagnosis within 2 years (524 screen-detected and 217 interval cancers) and 19 446 examinations without cancer. Transpara Detection and Transpara Risk achieved similar performance for detection (AUC for each, 0.92; 95% CI: 0.91, 0.93; P = .93) and outperformed the other models (all P < .001). Transpara Detection demonstrated the highest specificity (97.1%; 95% CI: 96.8, 97.3) at double-reading sensitivity (all P < .001). There was no evidence of a difference in specificity of Transpara Risk and RSNA Detection at this sensitivity (P = .29). For risk, Transpara Risk performed best (AUC, 0.81; 95% CI: 0.78, 0.84), with 49.8% sensitivity at 90% specificity (all P ≤ .002) for interval cancers. There was no evidence of a difference in AUC between Mirai Risk and Transpara Detection (P = .96). Conclusion Artificial intelligence-based mammographic detection and short-term breast cancer risk prediction models performed best in their intended settings. Keywords: Mammography, Breast, Computer Applications, Detection/Diagnosis, Screening, Technology Assessment, Model Validation Supplemental material is available for this article. © The Author(s) 2026. Published by the Radiological Society of North America under a CC BY 4.0 license.

Growing evidence suggests that circadian timing influences the efficacy of immune checkpoint inhibitors across multiple malignancies. However, evidence in extensive-stage small cell lung cancer (ES-SCLC) remains limited to a single East Asian cohort, and independent validation in other populations is lacking. We conducted a retrospective single-center cohort study of 107 patients with ES-SCLC treated with first-line platinum-etoposide plus atezolizumab or durvalumab. The time of day of administration (ToDA) was defined as the median start time of the first four immunotherapy infusions, and patients were categorized according to the cohort median ToDA. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The cohort median ToDA was 11:54. Patients treated before the median ToDA had significantly longer median PFS (9.07 vs. 7.23 months, p = 0.002) and OS (21.17 vs. 11.43 months, p = 0.002) than those treated later. In multivariable Cox regression analysis, later administration remained independently associated with shorter PFS (adjusted HR 1.63, 95% CI 1.03-2.58; p = 0.038) and OS (adjusted HR 1.65, 95% CI 1.00-2.71; p = 0.049), whereas objective response rates, treatment-related toxicity, and immune-related adverse events were comparable between groups. Morning administration of first-line chemoimmunotherapy was associated with significantly longer survival without increased toxicity in patients with ES-SCLC. These findings support growing evidence that circadian timing may influence immune checkpoint inhibitor efficacy and warrant prospective evaluation of treatment timing as a readily modifiable strategy to optimize immunotherapy delivery.

Choledochal cysts are congenital anomalies of the bile ducts that can lead to significant complications, such as cholangitis, liver fibrosis, and biliary obstruction. This study aims to evaluate the effectiveness and safety of percutaneous transhepatic biliary drainage (PTBD) in managing choledochal cysts with cholangitis in children.

This non-randomized interventional study included twelve paediatric patients with choledochal cysts and cholangitis treated over two years. Percutaneous transhepatic biliary drainage was performed to relieve biliary obstruction and stabilize patients before definitive surgical repair. Data were collected on patient demographics, clinical presentation, haematological and biochemical profiles, imaging findings, procedural details, and outcomes.

Of the 12 children, 8 (66.7%) were female, with a mean age of 55 ± 55 months. Jaundice was present in 11 (91.7%), abdominal pain in 10 (83.3%), vomiting in 9 (75.0%), and fever in 6 (50.0%). Baseline bilirubin and liver enzymes were elevated in all cases. Following PTBD, bilirubin levels decreased by 56% (median) by day 7, with 90% symptom resolution. Eight patients proceeded to surgery, while three had unfavorable outcomes. No major PTBD-related complications occurred. At follow-up, all surgically treated patients had normalized liver function, with histopathology showing periportal fibrosis in 50% of cases.

Percutaneous transhepatic biliary drainage was associated with clinical and biochemical stabilization in selected high-risk patients and may serve as an interim strategy before definitive surgery. Larger controlled studies are required to clarify its impact on outcomes.

Renal cell carcinoma (RCC) comprises approximately 90% of malignancy in the kidney. Early stage RCC is often asymptomatic. The majority of RCC are incidentally found on imaging ordered for unrelated medical indications. When diagnosed at an early stage, the survival or even cure rate is high. With more progressive stages, the outcome is less favorable. Tumor-induced angiogenesis affects blood flow in tumors such that patterns of perfusion can be utilized for diagnosis. Contrast-enhanced ultrasound (CEUS) takes advantage of the vascular architecture and provides a real-time assessment of vascularity, helping differentiate between solid and cystic masses. CEUS is a favorable tool for evaluation of indeterminate renal lesions due to its specificity for solid enhancing components, safety profile, and relatively low cost when compared with other imaging modalities including computed tomography (CT) or magnetic resonance imaging (MRI). This case highlights the sensitivity of contrast-enhanced ultrasound for detecting blood flow in a patient with papillary RCC.

The prognosis of metastatic uveal melanoma (mUM) remains poor, and immune checkpoint inhibitors (ICIs) show limited efficacy, with response rates typically below 5%. Tebentafusp, an immune therapy targeting the gp100 protein, is the first drug to improve overall survival (OS) in mUM. Somatic MBD4 deficiency induces a hypermutated phenotype in a fraction of UM cases and may predict benefit from ICIs.

We retrospectively analyzed patients with mUM carrying somatic or germline MBD4 alterations and treated with ICIs at Institut Curie (Paris, France). Clinical characteristics, treatments, and outcomes were collected.

Twelve patients received ICIs (nine pembrolizumab, two ipilimumab + nivolumab, one pembrolizumab + lenvatinib). Most (83%) had M1a liver-only disease. The overall response rate was 50% (two complete, four partial) with a disease control rate of 83%. The median follow-up was 22 months (range, 9.9-116.8), and within this time frame median progression-free survival and OS were not reached. At 12 months, 73% of patients were progression free, and the estimated 2-year OS was 86%.

We observed that, in patients with MBD4-mutated mUM, ICIs achieved a 50% response rate and prolonged survival, demonstrating strong and sustained clinical activity in this distinct molecular subgroup and exceeding outcomes reported with ICIs or tebentafusp.

Our findings support further evaluation of MBD4 mutation as a predictive biomarker and suggest that ICIs should be considered as a preferred first-line option in MBD4-mutated mUM.

Dependence receptors are distinctive type of receptors that induce a cellular state of dependence towards ligand availability. UNC5H receptors are notable examples of these receptors. They promote cell survival upon binding to their ligands, including netrin-1, whereas the absence of the ligand induces apoptosis. Unbound UNC5B promotes apoptosis through death-associated protein kinase (DAPK), while cell survival requires ligand binding. Previous studies have also shown the requirement of protein phosphatase 2A (PP2A) for this UNC5B-mediated apoptosis. Netrin-1 and its receptors are involved in nervous development, angiogenesis, and homeostatic maintenance of intestinal epithelium. UNC5H receptors are often down-regulated in various tumors, whereas several cancers have up-regulated netrin-1 expression, and both these conditions promote tumor cell survival. Interestingly, the interaction between netrin-1 and its receptors has been targeted in cancers to promote cancer cell death, reverse epithelial-to-mesenchymal transition, and inhibit metastasis and anti-cancer drug resistance. Here we discuss the mechanisms of signaling through UNC5H receptors and their role in normal cellular physiology and carcinogenesis. Furthermore, in the present review, we highlight the strategies that are currently being tested to target the netrin-UNC5H pathway for the treatment of cancer.

Tumor deposits (TDs) are recognized as adverse prognostic factors in colorectal cancer and are incorporated as N1c in the TNM staging system. Their significance in gastric cancer (GC), however, remains less clear.

This study aimed to investigate the association of TDs with pathological features and survival outcomes in GC.

We conducted a cross-sectional study of patients with pathologically confirmed GC treated at two tertiary hospitals in Tabriz, Iran, between January 2020 and December 2024. Clinical and pathological data, including tumor characteristics and survival status, were collected for the participants. TDs and their characteristics were also evaluated. Associations between the presence of TDs and clinicopathological features were analyzed using logistic regression models, while overall survival was assessed using Kaplan-Meier analysis and Cox proportional hazards regression.

The study included 256 patients (mean age 60.7±12.3 years; 61.3% male). TDs were present in 111 patients (43.4%). In multivariable analysis, pT category (OR=7.44, 95%CI: 2.22-24.89), pN category (OR=4.63, 95%CI: 1.97-10.86), and perineural invasion (OR=5.65, 95%CI: 2.40-13.29) were significant correlates of TDs. Kaplan-Meier analysis showed 1-, 3-, and 5-year overall survival rates of 93.7%, 75.7%, and 64.9%, respectively. Patients without TDs had significantly better survival compared to those with TDs (log-rank P<0.001). In multivariable Cox regression analysis, histological subtype (HR=2.07, 95%CI: 1.21-3.52), pT category (HR=4.68, 95%CI: 1.37-16.00), pN category (HR=2.79, 95%CI: 1.21-6.46), and the presence of TDs (HR=2.00, 95%CI: 1.06-3.75) were identified as independent predictors of poorer overall survival.

TDs were observed in a considerable proportion of GC cases and were associated with more aggressive pathological features and poorer survival. They may improve prognostic stratification, but further validation in larger multicenter studies is required.

Environmental exposure to heavy metals has been associated with cancer. Nonetheless, the effects of exposure to combined heavy metals on cancer mortality of urinary and gastrointestinal systems have not been examined. This study assessed the long-term association between environmental exposure to multiple heavy metals and cancer mortality rates in the digestive and urinary tracts. The death rates/100,000 inhabitants over 41 years were collected from Santo Amaro, the exposed town with a former lead smelter, and Ribeira do Pombal, the reference town, in Bahia, Brazil. The exposure duration, age and gender were considered predictors. The overall accuracy of the models ranged from 84 to 97%. For the population above 80 years, the probability of total mortality went from 20% in the first 6 years of exposure to over 70% after 20 years. The same trend was observed for the urinary system. For the digestive system, the mortality in the elders started after 15 years of exposure and peaked with a 30% probability after 35 years. In conclusion, environmental exposure to multiple heavy metals was linked to cancer-related deaths in the gastrointestinal and urinary tracts of the elderly population.

This study aimed to analyze trends in comorbidities associated with HIV-related mortality in Brazil from 2000 to 2022. This ecological time-series study used Mortality Information System data, including all deaths recorded under ICD-10 codes B20 to B24. Comorbidities were classified under ICD-10 chapters. Age-standardized mortality rates were calculated using the direct method. Trends were analyzed using Prais-Winsten regression. The mean mortality rate was 6.40 deaths per 100,000 inhabitants; for AIDS-defining conditions, the rate was 5.71 deaths per 100,000 inhabitants; and for non-AIDS-defining conditions, 0.65 deaths per 100,000 inhabitants. A decreasing trend was observed only for infectious diseases in Brazil (APC = -2.94; p-value < 0.001), a pattern not observed in some Northern and Northeastern states, where increasing trends were identified. Neoplasms showed a growing trend (APC = 4.69; p-value = 0.002), as did circulatory diseases (APC = 6.97; p-value = 0.002) in Brazil. High mortality rates for AIDS-defining conditions persist despite their overall declining trend, with increasing trends in some states.