Translational andrology and urology最新文献

Background: The global prevalence of lower urinary tract symptoms suggestive of benign prostate hyperplasia (LUTS/BPH) escalates, with obesity recognized as a major contributing factor. However, the association between the relative fat mass (RFM) and LUTS/BPH remains unexplored. This 7-year follow-up study aimed to investigate the cross-sectional and longitudinal relationships between RFM and LUTS/BPH.

Methods: Based on the China Health and Retirement Longitudinal Study (CHARLS) data, we interpolated missing values of covariates using multivariate imputation via chained equations grounded on the random forest method. Stratifying participants by tertiles of RFM, we employed multivariate binary logistic and restricted cubic spline (RCS) regressions to assess the odds ratio (OR) and dose-response relationship between RFM and LUTS/BPH. Subgroup and interactive analyses assessed covariate impacts. Sensitivity analysis involved stratifying RFM by median and quartiles and excluding males aged ≤60 years to confirm model robustness. A retrospective cohort [2011-2018] was used to investigate longitudinal associations, with additional cohorts [2011-2013, 2011-2015] for further sensitivity checks.

Results: A total of 6,253 males aged over 40 years were included in the 2011 baseline survey, with 4,321 observed in the 2018 follow-up. The final model revealed a positive correlation between high RFM and prevalent LUTS/BPH. Specifically, the risk for the third tertile group increased by a factor of 1.47 [95% confidence interval (CI): 1.16-1.87; P=0.001]. No significant interactive effects were observed. Linear trends were confirmed by RCS regression across demographics (P for overall <0.05). In the 2011-2018 cohort, the final model linked high RFM to a 1.41 times higher incidence of LUTS/BPH (95% CI: 1.11-1.80; P=0.003) in the third tertile subgroup. All sensitivity analyses consistently affirmed these positive associations.

Conclusions: Positive cross-sectional and longitudinal associations between RFM and LUTS/BPH were observed, underscoring RFM's potential as a valuable predictor for prompt detection targeting LUTS/BPH in aging males. Consequently, early management and treatment strategies could be implemented.

Background: Some studies suggest a potential association between plasma lipidome and erectile dysfunction (ED), but the underlying mechanism and whether circulating inflammatory proteins act as mediators remain unclear. The purpose of this study was to investigate the potential causal relationships between plasma lipidome, inflammatory proteins, and ED.

Methods: Plasma lipidome, circulating inflammatory proteins, and ED cases were identified based on the summary data from several large-scale genome-wide association studies (GWAS). The causal relationships of plasma lipidome and circulating inflammatory proteins with ED were explored by a bidirectional two-sample, two-sample Mendelian randomization (MR) method. The inverse variance weighted (IVW) method was used as the primary analytical method. MR-Egger and the weighted median (IVW) methods were utilized as supplementary analytical techniques. Sensitivity analyses including MR-Pleiotropy RESidual Sum and Outlier method (PRESSO), Cochran's Q test, and MR-Egger intercept test were conducted to address heterogeneity and horizontal pleiotropy.

Results: Ceramide (d42:2) and triacylglycerol (56:3) were found to be associated with an increased risk of ED, while phosphatidylethanolamine (O-18:1_18:2) and phosphatidylinositol (18:1_18:1) were linked to a decreased risk of ED. Interleukin-1α (IL-1α), IL-7, IL-17C, and the tumor necrosis factor (TNF) receptor superfamily member 9 (TNFRSF9) positively affected ED. Conversely, leukemia inhibitory factor and urokinase-type plasminogen activator (uPA) showed a negative impact. Mediation analysis indicated that the uPA mediated between Triacylglycerol (56:3) and ED, accounting for a mediation proportion of -14.71%.

Conclusions: There was a causal relationship between plasma lipidome and circulating inflammatory proteins with ED. Circulating inflammatory proteins appeared to mediate between triacylglycerol (56:3) levels and ED.

Background: Bladder cancer (BCa) is one of the most common tumors of the urinary system, imposing a significant societal burden. BCa is categorized into muscle-invasive BCa (MIBC) and non-MIBC (NMIBC) types. Radical cystoprostatectomy (RCP) is the standard treatment for MIBC and refractory NMIBC, but it can lead to serious side effects. Incidental prostate cancer (IPCa) is frequently found in RCP specimens, with varying incidence rates across ethnic groups, ranging from 7.3% to 60%. The clinical significance is unclear, and disparities in incidence and tumor characteristics exist within the Chinese population. The impact of IPCa on survival is debated, highlighting the need for research on its incidence and pathology for tailored interventions. This study aimed to compare the clinicopathological characteristics and prognostic significance of IPCa in RCP specimens taken from Chinese and Western BCa populations.

Methods: Data from patients who underwent RCP in our hospital between 2008 and 2022 were collated and compared to data from the Surveillance, Epidemiology, and End Results (SEER) database between 2008 and 2019. Chi-squared and non-parametric testing were conducted with survival analysis to investigate differences between IPCa traits and their impact on prognosis.

Results: Twenty-four IPCa cases were detected in 300 patients undergoing RCP, with a median age of 73 [interquartile range (IQR), 67-77] years. The median prostate-specific antigen (PSA) value was 2.81 (IQR, 1.19-4.81) ng/mL. 66.6% (n=16) had Gleason score (GS) ≤6 and all patients were stage T2. There were 315 IPCa patients in the 'Western' sample, with a median age of 68 (IQR, 63-74) years. The median PSA value was 1.9 (IQR, 0.9-4.1) ng/mL. 64.8% (n=204) had GS ≤6 and 93.0% (n=293) were stage T2. Comparative analysis showed that the clinicopathological features of IPCa were similar. Cox's regression analysis showed that T stage [hazard ratio (HR), 1.846; 95% confidence interval (CI): 1.394-2.444; P<0.001] and N stage (HR, 1.416; 95% CI: 1.011-1.984; P=0.04) of BCa were independent risk factors for cancer-specific survival (CSS). Advanced age (HR, 1.043; 95% CI: 1.018-1.069; P=0.001), T stage (HR, 1.569; 95% CI: 1.281-1.922; P<0.001), and N stage (HR, 1.317; 95% CI: 1.012-1.716; P=0.04) were independent risk factors for overall survival (OS). In the subgroup of patients with NMIBC, patients with clinically significant IPCa (csIPCa) had worse OS.

Conclusions: There were significant differences in IPCa detection rates between Chinese and Western populations. The main factors affecting survival were patient age and stage of BCa. However, in the NMIBC population, OS for patients with csIPCa appears poorer and further research is required.

Background: Sperm extraction by Microscopic Testicular Sperm Extraction (microTESE) has become the standard of care for sperm retrieval (SR) in men with non-obstructive azoospermia (NOA) but is costly and has a 40-50% chance of failure. Fine needle aspiration mapping (FNAM) can be performed prior to microTESE as a predictor of success to reduce the likelihood of failure to retrieve sperm but there is limited evidence that directly compares these methods. The objective of this study was to compare success rate of SR, pregnancy, and live birth rates in men who underwent upfront microTESE versus FNAM.

Methods: We performed a retrospective cohort study of men with NOA over a 10-year period from 2010 to 2019. The primary outcome was success of SR with secondary outcomes of pregnancy, and live-birth rates.

Results: Ninety men were included in the analysis. 60 in the FNAM group in 30 having upfront microTESE. In the FNAM group, 34/60 (56.7%) patients had positive fine needle aspiration (FNA) map for spermatogenesis. Of these 20/31 (64.5%) had FNAM-guided TESA/E, and 11/31 (35.5%) had microTESE. SR was successful in 30 of 31 men (96.8%). Overall SR rate was 54.4% and 56.7% in the FNAM group and upfront microTESE, respectively. There was no statistical difference in SR (P=0.65). The FNAM group had pregnancy and live-birth rates of 42.1% and 36.8%, respectively. The upfront microTESE group had pregnancy and live-birth rates of 36.7% each. χ² analysis revealed no statistical difference for both pregnancy (P=0.76) and live-birth rates (P=0.75).

Conclusions: FNAM carries high predictability and reliability in SR and can be performed prior to microTESE in NOA patients without change in fertility outcomes.

Background: A previously published study at Norrland University Hospital, Umeå, Sweden, found that in 29.5% of patients with urinary bladder cancer (UBC) who underwent cystectomy, incorrect cT-stage (clinical T-stage) was registered in the Swedish National Register of Urinary Bladder Cancer (SNRUBC). Tumor in bladder diverticulum (TIBD) and tumor-associated hydronephrosis (TAH) were common causes for misclassification. Our aim was to further investigate cT-staging, as well as pathoanatomical markers, in the SNRUBC, compared to detailed data from medical records in a larger, retrospective multicenter cohort. Our secondary objective was to describe the frequency of pathoanatomical markers in pathology reports (PAD) after transurethral resection of the bladder (TURb): variant histology (VH), concomitant carcinoma in situ (CIS), lymphovascular invasion (LVI) and perineural invasion (PNI).

Methods: Medical records of 630 patients planned for radical cystectomy in the years 2009-2022 in the Northern Healthcare Region, Region of Gävleborg and Region of Västmanland were reviewed. Factors impacting risk of misclassification of cT-staging were identified through logistic regression. In TURb pathology reports, all comments on pathoanatomical markers were identified. For each pathoanatomical marker, respectively, comments were then registered as positive or negative. The absence of a comment on a marker was registered as "not commented".

Results: A total discrepancy rate of 36.5% was found between validated cT-staging and the SNRUBC, of which 13.3% were upstaged from

Conclusions: The SNRUBC has a significant prevalence of misclassification of cT-staging with a large proportion due to TAH and TIBD. Misclassification of VH and CIS is also common. Improved guidelines could increase consistency. Total rates of recorded pathoanatomical markers in TURb-reports are low.

Background: Bladder urothelial carcinoma (BLCA) is a highly heterogeneous cancer with a wide range of prognoses, ranging from low-grade non-muscle-invasive bladder cancer (NMIBC), which has a good prognosis but a high recurrence rate, to high-grade muscle-invasive bladder cancer (MIBC), which has a poor prognosis. Glycosylation dysregulation plays a significant role in cancer development. Therefore, this study aimed to investigate the role of glycosyltransferases (GT)-related genes in the prognosis of BLCA and to develop a prognostic model based on these genes to predict overall survival (OS) and assess its clinical application.

Methods: The Cancer Genome Atlas (TCGA)-BLCA dataset, comprising 411 tumor and 19 normal samples. The validation set, GSE13507 from the Gene Expression Omnibus (GEO) database, included 165 primary bladder cancer samples with survival data. Differentially expressed GT-related genes (DEGRGs) in BLCA were identified in the training set. Predictive DEGRGs were used to construct risk score models by univariate Cox regression, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression. The predictive value of the models was assessed using Kaplan-Meier survival analysis and receiver operating characteristic (ROC) analysis in the training and validation sets. A nomogram was developed and its performance was evaluated with calibration curves. In addition, the relationship between the risk score and the tumor immune microenvironment was explored, and tumor immune dysfunction score (TIDE) and immune signature scores were used to predict the response to immunotherapy in BLCA patients.

Results: Thirty-three DEGRGs were identified in the comparison of BLCA patients with control samples. A risk score model was constructed based on 11 of these genes (GYS2, GALNTL6, GLT8D2, PYGB, B3GALNT2, GALNT15, ST6GALNAC3, ST8SIA6, CHPF, ALG9 and B3GALT2). The model performed well in predicting 3-, 5-, and 7-year overall survival (OS), with areas under the curve (AUC) of 0.65, 0.67, and 0.68, respectively. In addition, patients in the high-risk group had significantly lower survival than those in the low-risk group, and there were significant differences in immune status between the two groups. Based on age, tumor stage, T stage, and risk score, a Nomogram was constructed to predict the probability of OS, and the results of the calibration curves showed that the model had high predictive accuracy. Further analysis showed that the rejection score and TIDE were higher in the high-risk group, while the GT-related pathway was significantly upregulated in the high-risk group.

Conclusions: The 11 GT-related genes identified were associated with OS in BLCA patients, suggesting that the model has potential predictive value. At the same time, further research is needed to explore its role in clinical practice.

Background: Penile cancer is a rare malignancy treated via various surgical techniques guided by disease stage and grade with current guidelines suggesting partial or total penectomy for those with pT2 or greater. We report a case of a patient with pT2 squamous cell carcinoma (SCC) of the penis who underwent circumcision with left partial-glansectomy and en bloc resection of preputial mass with good oncological control while providing good urinary and sexual function.

Case description: An 82-year-old male presented to the clinic due to a mass that doubled in size in an 8-month timeframe. Treatment options were discussed with the patient including the risks and benefits of each electing wide-excision in glans-sparing fashion, possible partial penectomy. Given the possibility of low-grade verrucous carcinoma upon intraoperative exploration, ultimately, circumcision with left partial-glansectomy and en bloc resection of preputial mass was performed guided with intraoperative negative frozen sections. Patient's surgery and post-operative course were uncomplicated, followed with serial exams, and cross-sectional images showing no recurrence or metastasis.

Conclusions: Careful case selection with close postoperative follow-up monitoring for local recurrences, such as in this case, can allow patients to elect for organ-sparing partial glansectomy-when complete resection is feasible-as an acceptable option for oncological control in patients with pT2 penile cancer while providing good urinary and sexual function.

Background: Speckle-type POZ protein (SPOP), FAS-associated protein with death domain (FADD), and nuclear transcription factor-κB (NF-κB) have been shown to be associated with the development of prostate cancer (PCa). FADD has been shown to activate the NF-κB pathway to promote tumorigenesis, while SPOP has been shown to enhance the breakdown of FADD and inhibit the function of the NF-κB signaling pathway in non-small cell lung cancer. The existence of this mechanism has not yet been confirmed in PCa. This study aimed to explore the mechanism by which SPOP regulates FADD and the NF-κB signaling pathway in PCa.

Methods: Western blot was used to detect the presence of SPOP and FADD in both PCa cells and benign prostatic hyperplasia (BPH) cells. The biological behavior of the PC3 cells with altered levels of SPOP was examined using methods such as Cell Counting Kit 8, flow cytometry, and Transwell assay, and the effects of altering SPOP expression levels on the expression of FADD and NF-κB were assessed by western blot. The interaction between SPOP and FADD was detected by immunoprecipitation assay. The SPOP-overexpression PC3 cells were treated with MG132 inhibitor, and the expression of FADD was detected by western blot. A nude mice model of tumor of PCa with SPOP-overexpression was established, growth of the tumor was observed, and pathology of the tumor was diagnosed. Western blot was used to detect the expression of FADD and NF-κB in the tumor tissues.

Results: The PCa cells displayed decreased SPOP expression and increased FADD expression compared to the BPH cells (P<0.05). Additionally, the SPOP-silencing PC3 cells had higher levels of FADD and NF-κB expression than the SPOP-overexpression cells (P<0.05). Proliferation, migration, and invasion activities were lower in the SPOP-overexpression PC3 cells than the SPOP-silencing PC3 cells (P<0.05), and the apoptosis rate was higher in the SPOP-overexpression PC3 cells than the SPOP-silencing PC3 cells (P<0.05). There was an interaction between FADD and SPOP in the PC3 cells. After treatment with MG132, the expression of FADD rebounded compared with that before the treatment in the SPOP-overexpression PC3 cells (P<0.05). The volume and weight of the SPOP-overexpression PC3 tumors in the animal models were smaller than those of the control group (P<0.05). The pathological diagnosis revealed that the SPOP-overexpression tumors had more necrosis, and the expression of FADD and NF-κB in the PCa tumors was reduced when SPOP was overexpressed (P<0.05).

Conclusions: There may be a SPOP-FADD-NF-κB regulatory axis in PCa. SPOP facilitates the degradation of FADD, leading to a decrease in the activity of the NF-κB signaling pathway.

Background: The treatment of transplant ureteral stricture (TUS) has been a great challenge, and there is limited experience with indocyanine green (ICG) fluorescence-guided robotic Boari flap-pelvis anastomosis to identify ureteral stenosis segments (especially long-segment) and their postoperative blood supply. We report case series of ureteral strictures treated with ICG fluorescence-guided robotic Boari flap-pelvis anastomosis in our center.

Case description: We retrospectively collected clinical data of six patients diagnosed with long-segment even full-length TUS who underwent robotic Boari flap-pelvis anastomosis with the assistance of modified distribution of robotic ports and ICG fluorescence between June 2022 and June 2024, focusing on postoperative renal function, stenosis recurrence, and urinary fistulae. All patients, with long-segment even full-length TUS, underwent robotic Boari flap-pelvis anastomosis, with near infrared (NIR) fluorescence imaging using ICG fluorescence injection through the preplaced nephrostomy tube to find the pelvis and ureteric strictures of the transplant kidney. The median operative time was 181.5 min (range, 167-205 min) and the median blood loss was 65 mL (range, 50-120 mL). There were no high-grade complications (III-IV on Clavien-Dindo classification), and no patients were converted to open surgeries. The double-J stent was removed about two months after surgery, then the nephrostomy tube was removed about a week later. After six months of follow-up, no complications such as stenosis recurrence, urinary fistulae and urinary tract infection occurred. In addition, all patients did not complain for dysuria, frequent micturition, urgent urination, dysuria, or other symptoms in the follow-up.

Conclusions: Robot-assisted Boari flap-pelvis anastomosis guided by ICG fluorescence could be considered as a safe and reliable treatment for long-segment TUS. However, a large number of samples and long-term follow-up are still needed to further prove that it is the preferred option.

Background: Bladder cancer (BCa) is the most common neoplasm of the urinary system, and its high rates of progression and recurrence contribute to a generally poor prognosis, especially in advanced cases. It is reported that disulfidptosis is closely related with tumor proliferation. We aimed to construct a disulfidptosis-associated long non-coding RNA (lncRNA) signature that can predict prognosis and immune microenvironment in BCa.

Methods: We obtained RNA-seq data, clinical information, and mutation data of BCa patients from The Cancer Genome Atlas (TCGA) database. Based on Pearson correlation and uni-Cox regression analysis, we identified disulfidptosis-associated lncRNAs related with overall survival (OS). Then a prognosis signature based on seven disulfidptosis-associated lncRNAs was constructed by least absolute shrinkage and selection operator (LASSO) Cox regression analysis and multi-Cox regression analysis. We performed Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) analyses to examine biological functional of differentially expressed genes related to the risk model. We assessed the immune microenvironment and chemotherapeutic response of several drugs. Finally, the quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression level of the disulfidptosis-associated lncRNAs.

Results: We established a prognosis signature based on seven disulfidptosis-associated lncRNAs (AP003419.3, AL161891.1, AC234917.3, LINC00536, AL021707.6, AL445649.1 and AC104785.1). According to the signature, all patients were divided in high- and low-risk group and patients in low-risk group showed a significantly better prognosis. Moreover, the risk model was confirmed to be an independent prognostic factor with high accuracy. Immune cells and several immune checkpoints were more active in high-risk group and patients in this group had a higher tumor mutation burden (TMB) that those in low-risk group. The results of qRT-PCR demonstrated that expression level of the lncRNAs were all significantly different between BCa cell lines and normal urinary epithelial cells.

Conclusions: The disulfidptosis-associated lncRNA signature is a promising biomarker for predicting prognosis and characterizing the immune landscape in BCa, potentially guiding personalized treatment strategies.