Nature Reviews Urology最新文献

New research, published in Nature, shows that gut microbiota carcinogen metabolism could contribute to chemical-induced carcinogenesis in the bladder.

Chronic exposure to N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) induces bladder cancer in mouse models. Thus, the investigators used this model to examine the influence of gut microbiota on BBN-induced carcinogenesis and toxicokinetics.

In a new study published in JAMA Internal Medicine, the association between patients abandoning or reversing the pre-exposure prophylaxis (PrEP) prescription and the specialty of the prescribing clinician has been assessed. Overall, 37,003 patients who were prescribed PrEP were assessed using pharmacy claims data. The majority of patients (67%) received their prescription from primary care practitioners (PCPs), 10% from infectious disease specialists and 24% from other specialty clinicians. Patients who were prescribed PrEP by infectious disease specialists had lower odds of PrEP reversal (OR 0.90; 95% CI 0.81–0.99) and abandonment (OR 0.88; 95% CI 0.78–0.98) than patients receiving prescription from PCPs. These results indicate that PrEP compliance differs according to the prescribing clinician specialty and that PCPs, who are often the first patient access point to PrEP care, should be supported with PrEP education and resources.

PIWI-interacting RNAs (piRNAs) are crucial regulators of gene expression in male germ cells. In a study published in Nature Communications, the effect of disrupting piRNA biogenesis on human spermatogenesis was assessed. Analysis of exome data from >2,000 men with infertility led to the identification of biallelic variants in 14 genes related to the piRNA pathway in these men. These variants were associated with various testicular phenotypes, including non-obstructive azoospermia and cryptozoospermia. At a cellular level, dysfunction of piRNA-related genes resulted in reduced piRNA levels and de-repression of transposons in spermatogonia. The reproductive phenotypes of piRNA deregulation varied between mice and humans, highlighting that, although the piRNA pathway is conserved, species-specific research is still necessary. Results from this study show a prominent role of piRNA pathway genes in male infertility, providing potential targets for future investigations.

Measuring bladder volume is essential to assess bladder function for diagnosis and monitoring of lower urinary tract dysfunction, but currently available methods such as catheterization or ultrasonography are invasive and limited to the hospital setting. In a new study published in Nature Communications, a wireless and flexible ultrasonic bladder volume monitoring (UBVM) device was developed for continuous monitoring of bladder volume. The main advantage of this UBVM over currently available technologies is the wireless and wearable design, which eliminates the need for wired connections and enables unobtrusive measurements. This UBVM device combines flexible transducers with integrated electronics, in turn increasing accuracy. Using this UBVM in vivo in healthy volunteers resulted in a bladder volume estimation with a mean relative error of 11.17%. Pending comprehensive validation in a wide range of patients, this device has the potential to assist in the diagnosis and treatment of different lower urinary tract dysfunctions.

Intra-tumour heterogeneity in patients with metastatic castration-resistant prostate cancer (mCRPC) poses a challenge to treatment, owing to variability in tumour growth and response to therapy. Currently available tools such as response evaluation criteria in solid tumors (RECIST) and circulating tumour DNA (ctDNA) are useful methods to measure patient response to treatment but do not enable the assessment of individual tumour lesions with high resolution.

In a new study published in Med, the potential of ⁶⁸Ga-prostate-specific membrane antigen (PSMA) + ¹⁸F-fluorodeoxyglucose (FDG) paired positron emission tomography–computed tomography (PET–CT) was assessed to capture intralesional response heterogeneity (ILRH) and improve risk stratification in patients with mCRPC.

The function and value of specific sperm RNAs in apparently idiopathic male infertility are currently poorly understood. Whether differences exist in the sperm RNA profile between patients with infertility and fertile men needs clarification. Similarly, the utility of sperm RNAs in predicting successful sperm retrieval and assisted reproductive technique (ART) outcome is unknown. Patients with infertility and fertile individuals seem to have differences in the expression of non-coding RNAs that regulate genes controlling spermatogenesis. Several RNAs seem to influence embryo quality and development. Also, RNA types seem to predict successful sperm retrieval in patients with azoospermia. These findings suggest that sperm RNAs could influence decision-making during the management of patients with infertility. This evidence might help to identify possible therapeutic approaches aimed at modulating the expression of dysregulated genes in patients with infertility. Performing prospective studies with large sample sizes is necessary to investigate cost-effective panels consisting of proven molecular targets to ensure that this evidence can be translated to clinical practice.

Prostate Cancer Diagnosis and Treatment Enhancement through the Power of Big Data in Europe (PIONEER) is a European network of excellence for big data in prostate cancer. PIONEER brings together 34 private and public stakeholders from 9 countries in one multidisciplinary research consortium with the aim of positively transforming the field of prostate cancer clinical care by answering pressing questions related to prostate cancer screening, diagnosis and treatment. PIONEER has developed a unique state-of-the-art big data analytic platform by integrating existing data sources from patients with prostate cancer. PIONEER leveraged this platform to address prioritized research questions, filling knowledge gaps in the characterization, management and core outcomes of prostate cancer across the different disease stages. The network has benefited from sustained patient and stakeholder involvement and engagement, but many challenges remain when using real-world data for big data projects. To continue to advance prostate cancer care, data need to be available, suitable methodologies should be selected and mechanisms for knowledge sharing must be in place. Now acting as the prostate cancer arm of the European Association of Urology’s new endeavour, UroEvidenceHub, PIONEER maintains its goal of maximizing the potential of big data to improve prostate cancer care.

Clear-cell renal cell carcinoma (ccRCC) is a common urological malignancy with an increasing incidence. The development of molecular biomarkers that can predict the response to treatment and guide personalized therapy selection would substantially improve patient outcomes. Dysregulation of non-coding RNA (ncRNA) has been shown to have a role in the pathogenesis of ccRCC. Thus, an increasing number of studies are being carried out with a focus on the identification of ncRNA biomarkers in ccRCC tissue samples and the connection of these markers with patients’ prognosis, pathological stage and grade (including metastatic potential), and therapy outcome. RNA sequencing analysis led to the identification of several ncRNA biomarkers that are dysregulated in ccRCC and might have a role in ccRCC development. These ncRNAs have the potential to be prognostic and predictive biomarkers for ccRCC, with prospective applications in personalized treatment selection. Research on ncRNA biomarkers in ccRCC is advancing, but clinical implementation remains preliminary owing to challenges in validation, standardization and reproducibility. Comprehensive studies and integration of ncRNAs into clinical trials are essential to accelerate the clinical use of these biomarkers.