Current Urology最新文献

Background: Although genetic variants associated with bladder cancer (BCa) risk have been identified through hypothesis-driven and genome-wide association studies, a systematic understanding of BCa genetic susceptibility at the gene and pathway levels remains to be achieved.

Materials and methods: In this 2-stage functional genomics study, we used 5 independent tools for genome-wide gene mapping and ranking based on BCa genome-wide association studies summary statistics, followed by a meta-analysis of gene-level significance p values, to obtain a consensus gene ranking in terms of association with BCa. Subsequently, we performed preranked gene-set enrichment analysis to identify the functional pathways involved in BCa genetic susceptibility. Joint analysis with gene-set enrichment analysis, based on somatic alteration frequency, was performed to explore the pathway-level relationships between genetic susceptibility and somatic alterations in BCa.

Results: Other than the well-known BCa genes (such as FGFR3, MYC, TERT, CCNE1, and TP63), we additionally prioritized a set of novel genes likely to be genetically implicated in BCa development, including SETD2, a possible tumor suppressor gene involved in chromatin remodeling. We further demonstrated convergence between genetic associations and somatic alterations at both the gene (eg, FGFR3 and TERT) and pathway levels (eg, cell cycle and chromatin modification), as well as functional ontologies specifically implicated in germline predisposition to BCa (eg, CD8/TCR signaling, immune checkpoints, and cytokine signaling).

Conclusions: We identified several novel genes associated with BCa and demonstrated that genetic variants contribute to the development of BCa by affecting antitumor immunity, response to toxic exposure, and RNA and protein homeostasis and synergizing with somatic alterations in various cancer-related pathways.

Spatial transcriptomics, an increasingly prominent technique, has been extensively utilized to examine tumors within the digestive tract (such as liver and colorectal cancers) and the nervous system. However, its application in prostate cancer research remains comparatively limited. This article provides a detailed overview of the principles and features of spatial transcriptomics, particularly highlighting its applications in studying the tumor microenvironment, heterogeneity, and clinical implications in prostate cancer. Through a systematic review and analysis of current literature, we identify the main focus areas and limitations of existing research on spatial transcriptomics and suggest potential future research directions.

Background: There is no standard analgesic pathway after percutaneous nephrolithotomy. At our institution, an Enhanced Recovery After Surgery (ERAS) pathway was instated that included a preoperative erector spinae plane (ESP) block to improve pain control and minimize opioid usage in the postoperative setting.

Materials and methods: At our institution, an ERAS pathway was created for patients undergoing percutaneous nephrolithotomy. This pathway involved a preoperative ESP block and the replacement of opioids with multimodal analgesia. Patient charts were retrospectively reviewed and placed into 2 cohorts: one cohort participated in the ERAS pathway, whereas the other received traditional pain control. The primary outcome evaluated was postoperative morphine equivalents received. Secondary outcomes included nursing pain scores, opioid prescriptions for home, and quality of life. Descriptive statistics were performed by nonparametric Mann-Whitney U and χ ² tests for continuous and categorical variables, respectively.

Results: Sixty patients were identified in the ERAS cohort versus 70 in the traditional pain control cohort. There was a statistically significant difference in average postoperative morphine equivalents received (17.0 vs. 39.9, p < 0.01) and average postoperative nursing pain score (2.4 vs. 3.6, p < 0.01). Fifty-three percent (32/60) of patients in the ERAS cohort received an opioid prescription for home compared with 80% (56/70) in the traditional cohort (p < 0.01). There was no significant quality-of-life difference between the groups. No adverse patient events resulted from the block.

Conclusions: An ERAS pathway including a preoperative ESP block and multimodal analgesia decreased morphine equivalents received and nursing pain scores. Future randomized prospective studies with the ERAS protocol can be considered.

Background: With the rising incidence of prostate cancer (PCa), there is a global demand for assistive tools that aid in the diagnosis of high-grade PCa. This study aimed to develop a diagnostic support system for high-grade PCa using innovative magnetic resonance imaging (MRI) sequences in conjunction with artificial intelligence (AI).

Materials and methods: We examined image sequences of 254 patients with PCa obtained from diffusion-weighted and T2-weighted imaging, using novel MRI sequences before prostatectomy, to elucidate the characteristics of the 3-dimensional (3D) image sequences. The presence of PCa was determined based on the final diagnosis derived from pathological results after prostatectomy. A 3D deep convolutional neural network (3DCNN) was used as the AI for image recognition. Data augmentation was conducted to enhance the image dataset. High-grade PCa was defined as Gleason grade group 4 or higher.

Results: We developed a learning system using a 3DCNN as a diagnostic support system for high-grade PCa. The sensitivity and area under the curve values were 85% and 0.82, respectively.

Conclusions: The 3DCNN-based AI diagnostic support system, developed in this study using innovative 3D multiparametric MRI sequences, has the potential to assist in identifying patients at a higher risk of pretreatment of high-grade PCa.

Background/aims: Current guidelines suggest that the indications for pelvic lymph node (LN) dissection (PLND) during radical prostatectomy (RP) should rely on nomograms predicting their involvement. Positron emission tomography/computed tomography (PET/CT) with prostate-specific membrane antigen (PSMA) radioligand is gaining acceptance as routine diagnostic test before RP in patients with intermediate/high-risk prostate cancer (PC). In this study, we examined the effect of preoperative PET/CT on the accuracy of the nomograms.

Materials and methods: Patients with intermediate/high risk PC showing no extraprostatic disease on PET/CT-PSMA underwent RP with PLND and were followed postoperatively for at least 6 months. Patients with detectable (>0.1 ng/mL) postoperative prostate-specific antigen levels underwent re-evaluation with PET/CT-PSMA.

Results: A total of 70 patients underwent RP for intermediate (34 patients) or high-risk disease (36 patients). According to the Partin, MSKCC, and Briganti 2012 nomograms, positive LNs were expected in 7, 13, and 12 patients, respectively. At PLND, 1 positive LN was found in a single patient (p < 0.05 compared with the expected number of patients from all nomograms). Postoperatively, 10 patients developed detectable prostate-specific antigen levels. One patient exhibited radioligand uptake that could indicate LN involvement. Considering these 2 patients as failures, the negative predictive value of PSMA-PET/CT for LN involvement was 97.1%.

Conclusions: Preoperative PSMA-PET/CT with no extraprostatic uptake before RP in patients with intermediate to high-grade PC is highly accurate for ruling out LN involvement, superior to the routinely used nomograms. Its use induced stage migration, rendering predictive nomograms irrelevant.

Background: This study aimed to determine whether preoperative cognitive screening using the Mini-Cognitive Assessment Instrument (Mini-Cog) was useful for predicting the need for postoperative rehabilitation intervention in patients with bladder cancer who underwent radical cystectomy.

Materials and methods: We collected the medical records of consecutive patients who underwent radical cystectomy and preoperative cognitive screening based on the Mini-Cog test in our department between 2020 and 2021 (n = 114). Univariate and multivariate logistic regression analyses were used to identify the clinical risk factors for requiring rehabilitation intervention because of failure to wean postoperatively.

Results: The median age of the participants was 76 years, and 96 (84%) were male. Of the 114 patients, 31 (27%) required rehabilitation intervention for weaning. Based on the Mini-Cog test, the patients were classified into 2 groups: 22 (19%) had probable cognitive impairment (Mini-Cog score <3). Of the 22 patients with a Mini-Cog score of <3, 13 (59%) required rehabilitation intervention because of failure to wean postoperatively. In the multivariate analysis, being 75 years or older (odds ratio [OR], 9.7; 95% confidence interval [CI], 2.6-36.3; p < 0.001), a Mini-Cog score of <3 (OR, 3.7; 95% CI, 1.2-11.2; p = 0.02), and an operative time ≥310 minutes (OR, 3.6; 95% CI, 1.1-11.9; p = 0.04) were independent risk factors for requiring postoperative rehabilitation intervention.

Conclusions: Effective screening with the Mini-Cog test, a simple cognitive screening tool with only 2 components (delayed 3-word recall task and clock drawing), reflects not only cognitive function but also physical frailty and may lead to the establishment of appropriate rehabilitation programs during the perioperative period for early patient mobility after surgery.

In recent years, the detection urinary DNA methylation in bladder cancer has witnessed significant advancements. Important breakthroughs have been achieved in the diagnosis of bladder cancer through the use of DNA methylation biomarkers in urine. Several clinical studies have successfully established multiple biomarkers and developed reliable diagnostic models. Additionally, certain assay kits are certified by the Food and Drug Administration or the National Medical Products Administration and provide dependable tools for clinical applications. However, traditional techniques have limitations in terms of sample requirements, operational complexity, and stability. This review presents the application of novel technologies for the detection of urinary DNA methylation in bladder cancer, including microfluidic, digital polymerase chain reaction, and CRISPR technologies. The introduction of these innovative approaches holds promise for enhancing the early diagnosis and prognosis of bladder cancer. These advances are expected to drive further research and clinical applications in this field.

Background: To assess the efficacy of metastasis-directed external beam radiotherapy (MDT) in patients with castration-resistant prostate cancer (CRPC), we conducted a multicenter retrospective study.

Materials and methods: We retrospectively analyzed data from patients with metastatic CRPC treated with MDT between January 2013 and July 2023 across 14 hospitals. Patients who received palliative or local radiation therapy or had insufficient clinical data were excluded. The primary endpoint was the change in prostate-specific antigen (PSA) levels from pre- to post-MDT. Secondary endpoints included overall survival, time to next systemic therapy, PSA progression-free survival, and reduction of target lesions assessed radiographically.

Results: Among 579 patients with metastatic prostate cancer who received radiation therapy, 48 underwent MDT. The median follow-up period was 325 days, and the median patient age was 74 years. Metastasis-directed external beam radiotherapy target sites included bone (n = 34, 70.8%), lymph nodes (n = 11, 22.9%), local recurrence (n = 2, 4.2%), and other sites (n = 1, 2.1%). Of the 48 patients, 30 (62.5%) showed a decrease in PSA levels after MDT, and 20 (41.6%) achieved a PSA reduction greater than 50%. Among the 26 patients who underwent post-MDT radiographic evaluation, 11 (42.3%) demonstrated a reduction in target lesions. Median overall survival, PSA progression-free survival, and time to next systemic therapy for patients with and without a PSA response were 1307 versus 614 days (p = 0.038, log-rank test), 233 versus 98 days (p = 0.014, log-rank test), and 434 versus 450 days (p = 0.273, log-rank test), respectively. The median PSA doubling time was 4.1 months in PSA responders and 1.7 months in nonresponders.

Conclusions: Metastasis-directed external beam radiotherapy resulted in PSA reduction in 62.5% of patients with metastatic CRPC. Metastasis-directed external beam radiotherapy may be a suitable treatment option for patients with a favorable prognosis but may not benefit those with a poor prognosis and short PSA doubling time.

Background: Chronic prostatitis (CP)/chronic pelvic pain syndrome is the most common urological disorder in young and middle-aged men. A previous study showed that melatonin attenuates prostate inflammation through Sirt1-dependent suppression of the nonobese diabetic-like receptor thermal protein domain-associated protein 3 inflammasome in mouse models of experimental autoimmune prostatitis (EAP). However, the main differentially expressed proteins (DEPs) in melatonin-treated mice with EAP have not yet been fully identified.

Materials and methods: Mouse models of EAP were established. The pathological morphology of the prostate tissues was observed using hematoxylin-eosin staining. Chronic pelvic pain sensitivity was assessed using suprapubic allodynia. Inflammation-related cytokines were detected using an enzyme-linked immunosorbent assay. These methods were used to validate the successful establishment of the EAP mouse model. Tandem mass tag proteomics was used to identify the proteomic markers in melatonin-treated EAP mice. Next, we visualized the DEPs using bioinformatic analyses. Finally, we measured the expression of mitochondrial creatine kinase 1 and gap junction β-1, which were identified by the tandem mass tag in all groups, using Western blotting to explore the key proteins involved in the anti-inflammatory effects of melatonin on EAP.

Results: We identified 5910 proteins, with quantitative information available for over 85% of the total. We found 53 DEPs in mice between the EAP and control groups and 22 DEPs between the EAP-Melatonin and EAP groups. Bioinformatic analysis suggested significant alterations in immunosuppression, inflammatory chemotaxis, and energy metabolism signaling in EAP mice treated with melatonin. These alterations were confirmed using Western blotting.

Conclusions: Melatonin effectively relieves CP/chronic pelvic pain syndrome-related symptoms in mice with EAP. Mitochondrial kinases are potential key proteins in the treatment of EAP with melatonin, and these biomarkers may provide direction for studying the molecular mechanisms of melatonin in the treatment of CP.