Nature Reviews Urology最新文献

The clinical diagnosis of renal cell carcinoma (RCC) is constantly evolving. Diagnostic imaging of RCC relying on enhanced computed tomography (CT) and magnetic resonance imaging (MRI) is commonly used for renal mass characterization and assessment of tumour thrombosis, whereas pathology is the gold standard for establishing diagnosis. However, molecular imaging is rapidly improving the clinical management of RCC, particularly clear-cell RCC. Molecular imaging aids in the non-invasive visualization and characterization of specific biomarkers such as carbonic anhydrase IX and CD70 within the tumours, which help to assess tumour heterogeneity and status. Target-specific molecular imaging of RCCs will substantially improve the diagnostic landscape of RCC and will further facilitate clinical decision-making regarding initial staging and re-staging, monitoring of recurrence and metastasis, patient stratification and selection, and the prediction and evaluation of treatment responses.

The decline in male fertility correlates with the global rise in obesity and dyslipidaemia, representing significant public health challenges. High-fat diets induce metabolic alterations, including hypercholesterolaemia, hepatic steatosis and atherosclerosis, with detrimental effects on testicular function. Testicular tissue, critically dependent on lipids for steroidogenesis, is particularly vulnerable to these metabolic disruptions. Excessive lipid accumulation within the testes, including cholesterol, triglycerides and specific fatty acids, disrupts essential sperm production processes such as membrane formation, maturation, energy metabolism and cell signalling. This leads to apoptosis, impaired spermatogenesis, and abnormal sperm morphology and function, ultimately compromising male fertility. During spermiogenesis, round spermatids undergo extensive reorganization, including the formation of the acrosome, manchette and specialized filamentous structures, which are essential for defining the final sperm cell shape. In this Perspective, we examine the impact of high-fat diets on the cytoskeleton of spermatogenic cells and its consequences to identify the mechanisms underlying male infertility associated with dyslipidaemia. Understanding these processes may facilitate the development of therapeutic strategies, such as dietary interventions or natural product supplementation, that aim to address infertility in men with obesity and hypercholesterolaemia. The investigation of cytoskeleton response to lipid stress extends beyond male reproduction, offering insights with broader implications.

Early metastatic spread and clonal expansion of individual mutations result in a heterogeneous tumour landscape in metastatic urothelial cancer (mUC). Substantial molecular heterogeneity of common drug targets, such as membranous NECTIN4, FGFR3 mutations, PDL1 or immune phenotypes, has been documented between primary and metastatic tumours. However, translational and clinical studies frequently do not account for such heterogeneity and often investigate primary tumour samples that might not be representative in patients with mUC. We propose this as a potential factor for why many biomarkers for mUC have failed to be integrated into clinical practice. Fresh pre-treatment metastatic biopsies enable the capturing of prevailing tumour biology in real time. The characterization of metastatic tumour samples can improve response prediction to immunotherapy, the anti-NECTIN4 antibody–drug conjugate enfortumab vedotin and the FGFR inhibitor erdafitinib. Routine metastatic biopsy can thus improve the precision of identifying driver druggable alterations, thus improving treatment selection for patients with mUC.