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.

Risk-reducing mastectomy significantly decreases the incidence of breast cancer in women with a genetic predisposition. However, its effects on psychosocial and sexual well-being remain insufficiently explored, particularly among women without a previous diagnosis of breast cancer.

To evaluate the psychosocial and sexual well-being of women undergoing risk-reducing mastectomy with immediate breast reconstruction.

This observational, cross-sectional study involved the retrospective collection of clinical data and was conducted at a specialized center. Women aged >18 years, with no history of breast cancer, who underwent bilateral risk-reducing mastectomy with immediate implant-based reconstruction between 2018 and 2023 were included. Psychosocial and sexual well-being domains were assessed using the BREAST-Q™, with standardized scores ranging from 0 to 100. Descriptive analyses, Spearman's correlation, and nonparametric tests were performed, adopting a significance level of P < 0.05.

Twenty-eight patients were included. The mean age was 41.8 ± 9.6 years at the time of surgery and 45.5 ± 9.4 years at the time of assessment. Mean scores were 68.5 ± 20.4 for psychosocial well-being and 55.4 ± 17.8 for sexual well-being. A strong correlation was observed between the two domains (ρ = 0.81; p < 0.001). Early postoperative complications and the need for reoperations were associated with lower scores in both domains. Higher educational attainment was associated with better sexual well-being scores. No significant associations were found for the remaining variables.

Risk-reducing mastectomy with immediate reconstruction is associated with variable psychosocial and sexual outcomes, primarily influenced by postoperative complications and reoperations. These findings highlight the importance of incorporating quality-of-life assessment into the counseling and follow-up of these patients.

Metastatic castration‑resistant prostate cancer (mCRPC) remains an incurable disease characterized by relentless progression and universal resistance to standard therapies. The limited efficacy of immunotherapies in this malignancy reflects an immunosuppressive tumor microenvironment orchestrated by regulatory T cells, myeloid‑derived suppressor cells, tumor‑associated macrophages and cancer‑associated fibroblasts, along with androgen receptor signaling, metabolic reprogramming and spatially organized immune exclusion zones. The present review synthesized emerging evidence from single‑cell and spatial transcriptomics to propose a spatiotemporal coevolution paradigm, wherein resistance emerges not through linear genetic selection alone but through dynamic, reciprocal interactions among tumor cells, stromal components and immune populations across both temporal and spatial dimensions. The framework integrates clonal evolution dynamics, preexisting castration‑tolerant progenitors, fibroblast‑dominated barriers and metabolic crosstalk that collectively enforce immune evasion. Key therapeutic vulnerabilities, including YAP1‑TGF‑β1 axis disruption, PKMYT1 inhibition, metabolic targeting and biomarker‑guided patient stratification, are critically evaluated within this ecological context. Ultimately, the present review aimed to establish spatiotemporal co‑evolution as a unifying framework that transforms mCRPC from a uniformly fatal disease into a chronically manageable condition through precisely timed, spatially informed and mechanistically rational interventions.