Nature Reviews Urology最新文献

Approximately 20% of paediatric and adolescent/young adult patients with renal tumours are diagnosed with non-Wilms tumour, a broad heterogeneous group of tumours that includes clear-cell sarcoma of the kidney, congenital mesoblastic nephroma, malignant rhabdoid tumour of the kidney, renal-cell carcinoma, renal medullary carcinoma and other rare histologies. The differential diagnosis of these tumours dates back many decades, when these pathologies were identified initially through clinicopathological observation of entities with outcomes that diverged from Wilms tumour, corroborated with immunohistochemistry and molecular cytogenetics and, subsequently, through next-generation sequencing. These advances enabled near-definitive recognition of different tumours and risk stratification of patients. In parallel, the generation of new renal-tumour models of some of these pathologies including cell lines, organoids, xenografts and genetically engineered mouse models improved our understanding of the development of these tumours and have facilitated the identification of new therapeutic targets. Despite these many achievements, paediatric and adolescent/young adult patients continue to die from such rare cancers at higher rates than patients with Wilms tumour. Thus, international coordinated efforts are needed to answer unresolved questions and improve outcomes.

Anterior prostate cancers (APCs) are a group of impalpable neoplasms located in regions anterior to the urethra, which comprise the transition zone, apical peripheral zone and anterior fibromuscular stroma. These regions are typically undersampled using conventional biopsy schemes, leading to a low detection rate for APC and a high rate of false negatives. Radical prostatectomy series suggest prevalence rates of at least 10–30%, but transperineal systematic biopsy is ideal for diagnosis, particularly where multiparametric MRI is unavailable. Combined MRI-targeted and systematic biopsies demonstrate high concordance with final histopathology and lead to the fewest incidences of upgrading and upstaging at radical prostatectomy. Thus, the use of combined biopsy techniques has important implications for preoperative work-up and surgical planning, as APCs are associated with larger cancer volumes and a higher rate of positive surgical margins than posterior prostate cancer. Nevertheless, anterior tumour location might confer a relative resistance to stage progression, as APCs exhibit lower rates of extraprostatic extension, seminal vesical invasion and lymph node metastases than the more commonly seen posterior neoplasms. Few studies have examined the long-term outcomes of partial gland approaches to APCs, but MRI-targeted techniques have the potential to provide real-time intraoperative guidance and maximize the oncological safety of anterior focal treatment options in patients with APC.

Urological diseases and their varied forms of management warrant special attention in the setting of climate change. Regarding urological cancers, climate change will probably increase the incidence and severity of cancer diagnoses through exposures to certain environmental risk factors, while simultaneously disrupting cancer care delivery and downstream outcomes. Regarding benign urological diseases, a burgeoning body of work exists on climate-related heat waves, dehydration, urolithiasis, renal injury and infectious and vector-borne diseases. Adding to the potential effect on disease pathogenesis, many patients with urological diseases undergo high-tech, resource-intensive interventions, such as robotic surgery, and entail intensive longitudinal assessments over many years. These features incur a considerable carbon footprint, generate substantial waste, and can introduce vulnerabilities to climate-related weather events. Links exist between planetary health (the health of humans and the natural systems that support our health), climate change and urological disease and urological care providers face many challenges in the era of anthropogenic climate change. The next steps and priorities for research, management, and health care delivery include identification and prioritization of health care delivery strategies to minimize waste and carbon emissions, while supporting climate resilience. Examples include supporting telemedicine, limiting low-value care, and building resilience to minimize impacts of climate-related disasters to prepare for the challenges ahead.

Prostate cancer is a multifactorial disease influenced by various molecular features. Over the past decades, epigenetics, which is the study of changes in gene expression without altering the DNA sequence, has been recognized as a major driver of this disease. In the past 50 years, advancements in technological tools to characterize the epigenome have highlighted crucial roles of epigenetic mechanisms throughout the entire spectrum of prostate cancer, from initiation to progression, including localized disease, metastatic dissemination, castration resistance and neuroendocrine transdifferentiation. Substantial advances in the understanding of epigenetic mechanisms in the pathophysiology of prostate cancer have been carried out, but translating preclinical achievements into clinical practice remains challenging. Ongoing research and biomarker-oriented clinical trials are expected to increase the likelihood of successfully integrating epigenetics into prostate cancer clinical management.