Search Results (1,932)

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. Although the STRIDE regimen (durvalumab plus tremelimumab) has demonstrated an overall survival benefit in clinical trials, real-world evidence remains limited, particularly in Turkish clinical practice. This study aimed to evaluate the effectiveness and safety of first-line STRIDE therapy in patients with unresectable HCC treated in routine clinical practice. Methods: We conducted a retrospective multicenter study including patients with unresectable HCC who received first-line durvalumab plus tremelimumab through the Turkish national Early Access Program across 18 oncology centers. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method, and exploratory Cox regression analyses were performed to evaluate baseline prognostic factors. Results: Thirty-two patients were included. The median PFS was 7.25 months (95% CI, 3.68–22.29), and the median OS was 11.43 months (95% CI, 4.50–not reached). The underlying liver disease etiology was non-viral in 53.1% of patients, hepatitis B virus in 40.6%, and hepatitis C virus in 6.3%. Grade ≥ 3 treatment-related adverse events occurred in fewer than 10% of patients. Conclusions: In this multicenter real-world cohort, first-line durvalumab plus tremelimumab appeared to be a feasible treatment option and was generally well tolerated in patients with unresectable HCC. However, given the retrospective design, small sample size, and absence of a control group, these findings should be interpreted cautiously and require confirmation in larger prospective comparative studies. Full article

Background/Objectives: Empowerment strategies promoting healthy behaviors are important for preventing chronic diseases and cancer, while individual health responsibility (IHR) plays a significant role. Although widely discussed in the literature, the concept of IHR does not have clearly defined domains or a validated instrument for assessment. Its overlap with locus of control theory, self-motivation, and personality type creates further difficulties. Meanwhile, perception of one’s own responsibility for health is an intuitive, simple item to answer, reflecting a person’s belief related to this topic. Moreover, for ethical reasons, this concept cannot be separated from personal beliefs and should not be adjusted according to strict scales and externally imposed definitions. Therefore, this study aimed to: (1) explore whether there is an association between self-perception of IHR and preventive/risk-taking behaviors; and (2) examine socio-demographic factors associated with the IHR score and three self-perceived characteristics, namely self-perceived locus of control, health literacy, and health status. Methods: A cross-sectional study with 968 healthcare workers was conducted in a large, multidisciplinary hospital covering several behaviors (smoking, alcohol consumption, diet, and participation in a screening program for hepatitis C). IHR was evaluated on a scale from 1 to 10, where 1 meant “to very little extent” and 10 meant “to a great extent”. Results: The average IHR score was 8.80 (SD = 1.88). In the univariate analysis, the IHR score was significantly related to gender, age, education, marital status, and all three personal characteristics. In the multivariate analysis, the socio-demographic associations lost statistical significance. IHR maintained its association with the healthy diet score in the multivariable model (B = 0.113, p = 0.036). In the unadjusted analyses, the distribution of IHR differed between participants who declared alcohol consumption and those who declared abstinence (χ² = 17.157, p = 0.002). However, this association was not retained in the multivariable model. Self-perceived internal locus of control was negatively associated with screening acceptance, but not with IHR. The OR of 0.927 refers to a one-point increase on the 1–10 scale. Across the full observed scale range, this corresponds to an OR of 0.51 (95% CI: 0.29–0.89), indicating lower odds of screening acceptance among participants with higher perceived internal control. Because this estimate assumes linearity across the entire scale, it should be interpreted cautiously. Conclusions: The gap between perceived responsibility and actual behavior suggests that IHR messaging alone is unlikely to be sufficient. Future research should consider social desirability and external locus of control when analyzing IHR and health behaviors. Full article

Background: Germline PALB2 variants are associated with hereditary breast cancer risk, but their clinical impact in Central Asian populations remains largely uncharacterized. This case study aims to evaluate the clinical significance of PALB2 variants in two Kazakh women with early-onset breast cancer. Methods: Molecular genetic testing identified germline PALB2 pathogenic variants (NM_024675.4:c.18_22delGAAGC and NM_024675.4:c.1034T>G) in two Kazakh women with early-onset invasive ductal carcinoma. Clinical courses, treatment responses, and outcomes were followed. Results: Neither patient had a reported family history of breast or other malignancies. Patient 1, a 26-year-old pregnant woman, was diagnosed with stage IIIB luminal B, HER2-negative invasive ductal carcinoma and received neoadjuvant chemotherapy, radical surgery, radiotherapy, endocrine therapy, and subsequent treatment for metastatic disease. Despite an initial response, she developed extensive skeletal metastases and died from metastatic breast cancer. Patient 2, a 33-year-old woman, presented with de novo stage IV luminal B, HER2-negative invasive ductal carcinoma with hepatic metastases. Following multimodal treatment, including chemotherapy, surgery, radiotherapy, endocrine suppression, and systemic therapy for disease progression, she experienced further metastatic spread and ultimately died from breast cancer-related complications. Conclusions: Both patients exhibited aggressive clinical courses characterized by early disease onset, metastatic progression, and poor outcomes despite comprehensive treatment. These cases highlight the potential clinical significance of germline PALB2 variants in apparently sporadic breast cancer and underscore the importance of genetic testing, risk assessment, and genetic counselling in young breast cancer patients, particularly in underrepresented. Full article

Background/Objectives: Hepatic hemangiomas are the most common benign liver tumors, typically diagnosed confidently by their classic imaging features. However, a subset displays atypical characteristics that complicate diagnosis. We hypothesized that the term “atypical hemangioma” is used inconsistently and may contribute to both over-investigation of benign lesions and missed malignancies. Accordingly, this study aimed to assess the implications of the use of this term in radiology reports. Methods: This retrospective multicenter study reviewed 327 hepatic lesions labeled as atypical hemangiomas in radiology reports from two tertiary hospitals between 2013 and 2023. Two abdominal radiologists independently assessed imaging characteristics. Final diagnoses were based on imaging stability, histopathology or clinical follow-up. Results: Of the 327 lesions, 305 (93.3%) were benign and 22 (6.7%) malignant. Among the malignant lesions, 11 (50%) had no recommendations for further workup, and 10 (45%) did not mention malignancy in the differential diagnosis. Malignant lesions were significantly larger (mean size: 49.5–50.8 mm vs. 28.1–29.1 mm; p < 0.001), more likely to have ill-defined margins (50–54.5% vs. 17.9–18.1%; p ≤ 0.001), early heterogeneous enhancement (46.2% vs. ~9.5%; p < 0.001), and restricted diffusion (75–100% vs. 7.8–17.6%; p < 0.001). Among the benign lesions, 128 (42%) could have been confidently diagnosed at baseline, yet 62 of these lesions underwent unnecessary additional workup. Conclusions: The term “atypical hemangioma” is inconsistently used and associated with both delayed cancer diagnosis and excessive workup of benign lesions. Standardized terminology and risk-adapted strategies may improve diagnostic accuracy, optimize management, and minimize patient harm. Prospective validation of standardized imaging criteria is warranted. Full article

Background: Liver cancers are a major cause of morbidity and mortality in patients where effective, non-invasive treatment options remain limited. Objective: Histotripsy is a non-invasive, non-thermal, image-guided focused ultrasound method of ablation that mechanically disrupts cells and offers a range of potential advantages over other ablation modalities. The lack of physiologically and anatomically relevant animal models of human liver cancer has significantly hindered biomedical device development, including histotripsy. Methods: To address these limitations, we developed a clinically relevant large animal orthotopic, dual-tumor model of human liver cancer and utilized these unique animals to evaluate the safety and efficacy of histotripsy. Here, we utilized immunocompromised pigs with genetic modifications in their IL-2RG and RAG2 genes and orthotopically engrafted human hepatocellular carcinoma (HepG2/C3A) and pancreatic adenocarcinoma (Panc-1) cells within the liver. The models were designed to recapitulate primary and metastatic liver tumor phenotypes. Results: Histotripsy enabled real-time visualization of the treatment by the formation of bubble clouds and accurate targeting of the lesions. Histological analysis confirmed the engraftment of tumor cells and the ablation of targeted tissue. Serum biomarkers demonstrated no significant differences in bilirubin, ALT, ALKP, or CK post-treatment, suggesting that histotripsy treatment was well tolerated with minimal hepatic dysfunction or hepatocellular injury. Conclusions: These findings establish a novel, clinically relevant porcine model of primary and metastatic liver tumors and demonstrate the safety and feasibility of using this model for evaluating histotripsy as a noninvasive modality for precise tumor ablation. Full article

Oncogenic viruses contribute to approximately 20% of human cancers globally, with their impact falling disproportionately on populations in Sub-Saharan Africa. In this region, cervical cancer, hepatocellular carcinoma, endemic Burkitt lymphoma, and Kaposi sarcoma represent major causes of cancer-related morbidity and mortality, driven by persistent infection with human papillomavirus (HPV), hepatitis B and C viruses (HBV/HCV), Epstein–Barr virus (EBV), Kaposi sarcoma-associated herpesvirus (KSHV), and human T-lymphotropic virus-1 (HTLV-1). This review synthesizes current insights into the immunological mechanisms that underpin viral carcinogenesis in Africa, emphasizing how defective viral clearance, chronic immune activation, and immune evasion arise from the convergence of region-specific co-infections, host genetic diversity, and environmental exposures. We examine the mechanistic roles of HIV-associated CD4⁺ T cell depletion, malaria-induced perturbation of antiviral T cell immunity, helminth-driven T helper 2 polarization, and tuberculosis-associated inflammatory signaling in promoting viral persistence and malignant transformation. In addition, the influence of the extensive diversity of African human leukocyte antigens (HLA) and cytokine gene polymorphisms on antiviral immune responses and cancer susceptibility was discussed. We also assessed how virus-associated tumors establish profoundly immunosuppressive microenvironments characterized by impaired antigen presentation and the dominance of immune checkpoint pathways. Finally, we examined how gaps in vaccination, screening, and diagnostic capacity intersect with immunological vulnerability across Africa, contributing to the burden of infection-associated cancers. These challenges position Africa as a critical setting for developing targeted, genotype-inclusive public health interventions and reducing global cancer disparities through advances in immunoprevention and immunotherapy. Full article

Background/Objectives: PTEN Hamartoma Tumour Syndrome (PHTS) is a rare inherited disorder caused by germline PTEN mutations, presenting with cancer predisposition and neurodevelopmental abnormalities, including macrocephaly. PTEN functions as a tumour suppressor by regulating the PI3K/AKT/mTOR pathway and contributes to cellular adhesion, migration, and genomic stability. As no curative therapy exists, gene therapy represents a promising avenue to correct the underlying genetic defect. Methods: In this study we evaluated the therapeutic potential of AAV9-mediated PTEN gene delivery in a Pten^Δ5/+ mouse model, which is predominantly characterized by progressive lymphoid hyperplasia leading to lymph node tumour development, as well as hepatic focal lesions and macrocephaly. Results: Systemic vector delivery did not improve lymph node enlargement which represents the predominant disease phenotype in the Pten^Δ5/+ mice at the doses tested, due to restricted vector biodistribution, but it did effectively rescue the hepatic lesions, including steatosis and steatohepatitis-like changes. Mechanistically, AAV-mediated PTEN expression significantly reduced elevated p-AKT levels, indicating attenuated hyperactivation of the PI3K/AKT/mTOR pathway. Additionally, intracranial delivery of the same vector in Pten^Δ5/+ mouse neonates ameliorated macrocephaly without apparent adverse effects. Conclusions: These findings highlight the therapeutic potential of AAV9-mediated PTEN gene therapy in PHTS, particularly for hepatic and neuroanatomical manifestations. Optimization of vector biodistribution and transduction efficiency will be critical for clinical translation. Full article

Background/Objectives: Prostate cancer is one of the most common non-skin solid malignancies among male solid organ transplant recipients (SOTRs), in whom radical prostatectomy is technically demanding. We report the first use of indocyanine green (ICG) fluorescence for simultaneous transplanted-ureter identification and renal graft vascular mapping during robot-assisted radical prostatectomy (RARP), and the first use of the CMR Versius^® platform in a SOTR. Methods: Retrospective case series of four consecutive male SOTRs (two renal [RTRs], two hepatic) undergoing RARP. In both RTRs, a dual-route ICG protocol was used on the da Vinci Xi with Firefly^® imaging: pre-docking intraureteral ICG via a ureteral catheter for ureter identification, plus an intravenous ICG bolus for graft vascular mapping and cortical perfusion. One hepatic recipient was operated with the CMR Versius^® system using an infra-umbilical port configuration to avoid the chevron transplant scar. Results: All four procedures were completed robotically without conversion. Median operative time was 176 min and median estimated blood loss 350 mL. Surgical margins were negative (R0) in all four; final pathology was pT3aN0 in three and pT2N0 in one, although in the renal recipients nodal staging reflected a contralateral-only dissection. PSA was undetectable at three months in all patients. One hepatic recipient later developed biochemical recurrence, managed with salvage radiotherapy and androgen deprivation therapy, with subsequent undetectable PSA. One hepatic recipient had a Clavien–Dindo IIIa complication. No graft dysfunction occurred. Conclusions: ICG-guided RARP and the CMR Versius^® platform appear technically feasible in carefully selected solid organ transplant recipients treated at an experienced multidisciplinary centre, with no graft-related complications observed in this small initial series. These preliminary findings require validation in larger, multicenter studies before general safety and oncological efficacy can be established. Full article

The endocannabinoid system (ECS) is increasingly recognized as a central regulator of immune homeostasis, integrating neural, metabolic, and immune signaling to maintain physiological equilibrium. This Perspective examines the “therapeutic paradox” of endocannabinoid immunomodulation, whereby anti-inflammatory and tissue-protective effects are mechanistically linked to transient immunosuppression. Although cannabinoid receptor 2 (CB2) is the primary mediator of immune regulation, growing evidence indicates that cannabinoid receptor 1 (CB1) also contributes to inflammatory control in both the central nervous system and peripheral tissues. Activation of CB2 suppresses inflammatory signaling through Gi/o-mediated inhibition of adenylate cyclase, reduced cyclic adenosine monophosphate (cAMP) signaling, and repression of nuclear factor kappa B (NF-κB)-dependent transcription. While these mechanisms limit pathological inflammation and promote tissue protection, they simultaneously attenuate innate and adaptive immune functions required for effective pathogen clearance. Across neuroinflammatory disorders, inflammatory bowel disease, hepatic injury, sepsis, cancer, and systemic inflammatory syndromes, the ECS shifts immune responses toward resolution at the cost of reduced antimicrobial readiness. We synthesize the molecular mechanisms underlying this therapeutic paradox, including macrophage polarization, lymphocyte reprogramming, and tissue-specific immune adaptations, and discuss strategies for developing endocannabinoid-based therapeutics that preserve anti-inflammatory efficacy while minimizing immunosuppressive liabilities. Full article

Hepatic malignancies account for a substantial portion of global cancer mortality, with hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (IHC), and metastatic liver disease representing the most common diagnoses. While surgical resection and liver transplantation remain curative options for eligible patients, most patients are diagnosed at stages unsuitable for surgery. This has shifted medical management towards locoregional therapies (LRTs) which are often catheter-directed. Of these interventions, the use of conventional end-hole catheters for therapeutic infusion has been a mainstay of treatment, but this method is constrained by retrograde particle escape and elevated tumoral interstitial fluid pressure. Together, these factors limit drug penetration into the tumor microenvironment. Pressure-enabled drug delivery (PEDD), achieved through balloon-occlusion or microvalve-based catheter platforms, has emerged as a strategy to overcome these limitations. This narrative review synthesizes current evidence regarding PEDD and contextualizes its role within the broader LRT landscape. Preclinical studies and early clinical data illustrate improved drug-delivery characteristics, acceptable safety profiles, and highlight the potential for adaptation to regional immunotherapy regimens. However, while PEDD represents a promising advance in catheter-based hepatic oncologic therapy, prospective randomized comparisons against conventional infusion remain limited, and significant investigation is needed to establish its definitive role in interventional oncology. Full article

Background/Objectives: Colorectal liver metastases (CRLMs) are a major contributor to recurrence and mortality in colorectal cancer (CRC), with approximately a quarter of patients developing liver metastases over the course of the disease. Bone-marrow-derived myeloid lineages are sent into the circulatory system and colonize pre-metastatic niches, yet the transcriptional programs by which they establish a pro-metastatic microenvironment remain incompletely defined. Methods: Using an MC38 splenic-injection CRLM mouse model, we generated single-cell RNA sequencing (scRNA-seq) profiles of FACS-sorted CD11b⁺Gr1⁺ bone marrow myeloid cells, together with bulk RNA sequencing profiles of bone marrow and peripheral blood. Downstream analyses were performed in silico, including clustering and annotation, trajectory inference, cell–cell communication analysis, weighted gene co-expression network analysis (WGCNA), and pathway enrichment, with subset specificity examined against a public dataset of E. coli (Escherichia coli)-infected mice. Results: Within the CD11b⁺Gr1⁺ compartment, a CCR2⁺ neutrophil-like population (Ly6g⁺S100a8/9⁺) emerging during terminal differentiation was identified, which was enriched in CRLM mice but nearly absent in controls. Communication inference revealed an FN1-CD44 interaction involving mature neutrophils, which was associated with an epithelial–mesenchymal transition signature and upregulation of Tgfb1 and Il1b. This subpopulation was not recovered in the infection dataset, suggesting relative specificity to CRLMs. Conclusions: Within the constraints of a splenectomized hepatic colonization model, integrated transcriptomic analysis highlighted a CCR2⁺ bone marrow neutrophil-like population as a candidate contributor to CRLM, challenging the view that CCR2⁺ pro-metastatic myeloid cells are exclusively monocytic and suggesting candidate biomarkers and therapeutic targets for further study. Full article

Background: Tuberculosis (TB) remains a leading cause of global morbidity and mortality, yet its impact extends far beyond microbiological cure. Many TB survivors experience persistent structural lung damage or functional impairment consistent with post-TB lung disease, while growing evidence highlights long-term non-respiratory health outcomes. Synthesizing evidence across lung and non- respiratory health outcomes, along with their risk factors, is critical to inform long-term TB care. Methods: We conducted a scoping review including systematic reviews reporting on post-TB long-term health outcomes. A search was performed in PubMed/MEDLINE on 27 July 2025, using terms related to “tuberculosis,” “systematic review,” “meta-analysis,” “sequelae” and “long-term health outcomes,” without language restrictions. Results: Nine systematic reviews met inclusion criteria. Most focused on pulmonary outcomes and consistently demonstrated that TB is associated with chronic airflow obstruction, reduced lung function, and an increased long-term risk of lung cancer, although residual confounding from environmental, clinical, and socioeconomic factors cannot be excluded. While younger adults are more prone to developing COPD after TB in high TB burden settings, older individuals face a higher risk of broader post-TB lung sequelae. Evidence suggested that TB survivors are at increased risk of non-respiratory complications. HIV co-infection, low CD4 counts, older age, pre-existing hepatitis, prior TB treatment, and hypoalbuminemia were associated with post-TB liver injury, while baseline hearing impairment and HIV co-infection increased the likelihood of post-TB hearing loss. TB was also linked to elevated risk of several non-pulmonary cancers, including oesophageal, cervical, hematological, pancreatic, and gastric malignancies, with the highest risk within the first year after TB diagnosis and persisting, though attenuated, in subsequent years. Conclusion: TB should be viewed as a chronic condition with enduring lung and non-respiratory health outcomes. TB survivors face increased risks of COPD, lung cancer, and a range of non-respiratory health outcomes, including hepatic and auditory complications, particularly among high-risk groups, such as those living with HIV infection, along with baseline hearing and hepatic impairment. Public health programmes must extend care beyond microbiological cure to include integrated, post-TB long-term monitoring of lung, hepatic and hearing across all ages, including malignancy surveillance, after baseline assessments to identify high-risk TB survivors. Future research should also elucidate risk factors for post-TB malignancy, and clarify the relationship between neurological, renal, and musculoskeletal sequelae and TB to inform evidence-based TB survivorship care. Full article

Background: Mucinous adenocarcinoma (MAC) of the colorectum is a biologically distinct histological subtype whose prognostic significance may vary substantially according to primary tumor location. The impact of anatomical site on clinicopathological characteristics and long-term survival in MAC remains incompletely characterized. This study aimed to evaluate the influence of tumor location on oncological outcomes in patients with mucinous colorectal cancer using a large population-based dataset. Methods: Patients diagnosed with mucinous colorectal adenocarcinoma between 2000 and 2023 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Operated patients were stratified by anatomical location into three groups: right colon (cecum, ascending colon, hepatic flexure, transverse colon), left colon (splenic flexure, descending colon, sigmoid colon, rectosigmoid junction), and rectum. The primary endpoints were overall survival (OS) and cancer-specific survival (CSS). Survival analyses were performed using the Kaplan–Meier method with log-rank testing. Multivariable Cox proportional hazards regression was used to assess the independent association of tumor location with survival outcomes, adjusting for age at diagnosis, year of diagnosis, sex, AJCC (American Joint Committee on Cancer) stage, tumor grade, receipt of radiotherapy and chemotherapy. Temporal trends in survival were evaluated across four consecutive diagnostic periods: 2000–2005, 2006–2011, 2012–2017, and 2018–2023. Results: A total of 40,698 patients with mucinous colorectal cancer were identified, of whom 40,174 underwent cancer-directed surgery (right colon n = 25,317; left colon n = 10,408; rectum n = 4449). The right colon was the predominant site of disease (62.9%). Median age was highest in the right colon group (74.0 years) and lowest in the rectum (65.0 years), while female sex predominated in right-sided tumors (55.7%) and male sex in rectal tumors (61.1%). Chemotherapy and radiotherapy utilization were markedly higher in the rectal group (68.6% and 64.5%, respectively) compared with the right colon (28.8% and 1.1%). Median OS was equivalent in the right and left colon groups (87.0 months each) but declined to 80.0 months in the rectal group. All pairwise CSS comparisons were statistically significant (all p < 0.001). On multivariable analysis, using the right colon as reference, the adjusted hazard ratios for CSS were 1.33 (95% CI: 1.28–1.39) for the left colon and 1.45 (95% CI: 1.34–1.57) for the rectum (both p < 0.001). Despite receiving the highest rates of multimodal therapy, rectal MAC demonstrated the worst long-term CSS across all anatomical groups. Temporal analyses revealed consistent CSS improvements in right-sided and left-sided MAC over the study period, whereas rectal MAC showed a non-linear trajectory with a plateau in the most recent diagnostic cohort (2018–2023). Conclusions: Mucinous colorectal adenocarcinoma demonstrates substantial biological and prognostic heterogeneity according to anatomical tumor location. Right-sided MAC was the most prevalent subtype and exhibited superior cancer-specific survival despite older patient age and lower treatment intensity. Rectal MAC demonstrated the worst long-term outcomes despite high utilization of multimodal neoadjuvant therapy, consistent with the established reduced responsiveness of mucinous tumors to conventional chemoradiotherapy. These findings underscore the necessity of incorporating anatomical location and tumor biology into individualized risk stratification and therapeutic planning for patients with mucinous colorectal cancer. Full article

Primary liver malignancies, including hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and combined hepatocellular cholangiocarcinoma, remain major causes of cancer-related morbidity and mortality worldwide. Although systemic therapies have advanced substantially, intrahepatic tumor progression, liver failure, and portal hypertension continue to drive adverse outcomes in many patients. Interventional radiology plays a central and expanding role in the multidisciplinary management of these tumors by providing image-guided locoregional therapies for local tumor control, downstaging, bridging transplantation or resection, palliation, and potential survival benefit. This narrative review summarizes current evidence and technical considerations for major locoregional approaches, including radiofrequency ablation, microwave ablation, cryoablation, transarterial chemoembolization, transarterial radioembolization, endobiliary therapies, stereotactic body radiation therapy, irreversible electroporation, histotripsy, high-intensity focused ultrasound, hepatic arterial infusion, and brachytherapy. Interventional radiology also contributes to preoperative liver optimization through portal vein embolization, liver venous deprivation, lobar radioembolization to induce contralateral hypertrophy, and, in some patients, portal decompression before hepatic resection. For hepatocellular carcinoma, ablation and transarterial therapies are integrated into stage-based treatment algorithms and may provide curative-intent treatment in some patients. In intrahepatic cholangiocarcinoma, locoregional therapies provide meaningful disease control and may prolong survival, particularly when combined with systemic therapy. In combined hepatocellular cholangiocarcinoma, treatment remains individualized because of limited prospective data and heterogeneous tumor biology. Beyond cytoreduction, locoregional therapies can modulate the tumor immune microenvironment through immunogenic cell death, antigen release, cytokine signaling, and vascular remodeling, providing a rationale for combination strategies with immune checkpoint inhibitors, anti-angiogenic agents, and targeted therapies. As treatment paradigms evolve, the future of interventional radiology in primary liver cancer will depend on appropriate patient selection, optimized dosimetry and technique, integration with molecular and immunologic biomarkers, and coordinated multidisciplinary care. Full article

Purpose: Nucleotide metabolism plays a critical role in cancer development, but the prognostic significance of genetic variants in nucleotide metabolism genes for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients remains unclear. Methods: We performed Cox proportional hazards regression analyses to evaluate the association between genetic variants in 94 nucleotide metabolism-related genes and overall survival (OS) in 866 HBV-HCC patients. To assess the potential biological relevance of the identified variants, the Bayesian false discovery probability and false-positive report probability were applied for multiple testing correction. Results: Two independent SNPs, DCTD rs17074255 G>A (HR = 1.22, 95% CI: 1.06–1.40, p = 0.005) and ENTPD2 rs3763662 G>A (HR = 1.18, 95% CI: 1.03–1.34, p = 0.015), were significantly associated with OS. A significant dose-dependent association between the number of risk genotypes and poorer OS was observed (P_trend < 0.001). Luciferase reporter assays demonstrated allele-specific regulatory effects of rs3763662 on ENTPD2 expression (p < 0.001). DCTD and ENTPD2 mRNA expression levels were significantly elevated in HCC tumors in the UALCAN database and in our 103 paired samples. Higher expression levels of both genes were associated with poorer survival in the TCGA cohort (p = 0.003 and p < 0.001). Conclusions: Our findings suggest that ENTPD2 rs3763662 (supported by direct functional evidence) and DCTD rs17074255 (supported by eQTL and expression associations) may serve as potential prognostic indicators for HBV-HCC through the regulation of mRNA expression. These findings provide new insights into the role of nucleotide metabolism-related genetic variation in HBV-HCC progression and may facilitate prognostic assessment, pending replication in independent cohorts. Full article