American journal of clinical and experimental urology最新文献

Background: Cancer detection presents challenges regarding invasiveness, cost, and reliability. As a result, exploring alternative diagnostic methods holds significant clinical importance. Urinary metabolomic profiling has emerged as a promising avenue; however, its application for cancer diagnosis may be influenced by sample preparation or storage conditions.

Objective: This study aimed to assess the impact of sample storage and processing conditions on urinary volatile organic compounds (VOCs) profiles and establish a robust standard operating procedure (SOP) for such diagnostic applications.

Methods: Five key variables were investigated: storage temperatures, durations, freeze-thaw cycles, sample collection conditions, and sample amounts. The analysis of VOCs involved stir bar sorptive extraction coupled with thermal desorption-gas chromatography/mass spectrometry (SBSE-TD-GC-MS), with compound identification facilitated by the National Institute of Standards and Technology Library (NIST). Extensive statistical analysis, including combined scatterplot and response surface (CSRS) plots, partial least squares-discriminant analysis (PLS-DA), and probability density function plots (PDFs), were employed to study the effects of the factors.

Results: Our findings revealed that urine storage duration, sample amount, temperature, and fasting/non-fasting sample collection did not significantly impact urinary metabolite profiles. This suggests flexibility in urine sample collection conditions, enabling individuals to contribute samples under varying circumstances. However, the influence of freeze-thaw cycles was evident, as VOC profiles exhibited distinct clustering patterns based on the number of cycles. This emphasizes the effect of freeze-thaw cycles on the integrity of urinary profiles.

Conclusions: The developed SOP integrating SBSE-TD-GC-MS and statistical analyses can serve as a valuable tool for analyzing urinary organic compounds with minimal preparation and sensitive detection. The findings also support that urinary VOCs for cancer screening and diagnosis could be a feasible alternative offering a robust, non-invasive, and sensitive approach for cancer screening.

Lower urinary tract dysfunction (LUTD) encompasses a range of debilitating conditions that affect both sexes and different age groups. Understanding the underlying neurobiological mechanisms contributing to LUTD has emerged as a critical avenue for the development of targeted therapeutic strategies. Brain-derived neurotrophic factor (BDNF), a prominent member of the neurotrophin family, has attracted attention due to its multiple roles in neural development, plasticity, and maintenance. This review examines the intricate interplay between neurobiological factors and LUTD, focusing on the central involvement of BDNF. The review emphasizes the bidirectional relationship between LUTD and BDNF and explores how LUTD-induced neural changes may affect BDNF dynamics and vice versa. Growth factor therapy and the combined administration of controlled release growth factors and stem cells are minimally invasive treatment strategies for neuromuscular injury. Among the many growth factors and cytokines, brain-derived neurotrophic factor (BDNF) plays a prominent role in neuromuscular repair. As an essential neurotrophin, BDNF is involved in the modulation of neuromuscular regeneration through tropomyosin receptor kinase B (TrkB). Increasing BDNF levels facilitates the regeneration of the external urethral sphincter and contributes to the regulation of bladder contraction. Treatments targeting the BDNF pathway and sustained release of BDNF may become novel treatment options for urinary incontinence and other forms of lower urinary tract dysfunction. This review discusses the applications of BDNF and the theoretical basis for its use in the treatment of lower urinary tract dysfunction, including urinary incontinence (UI), overactive bladder (OAB), and benign prostatic hyperplasia (BPH), and in the clinical diagnosis of bladder dysfunction.

The decline of urethral function with advancing age plays a major role in urinary incontinence in women, impairing quality of life and economically burdening the health care system. However, none of the current urinary incontinence treatments address the declining urethral function with aging, and the mechanisms by which aging impacts urethra physiology remain little known or explored. Here, we have compared functional, morphometric, and global gene expression of urethral tissues between young and old female mice. Bladder leak point pressure (LPP) measurement showed that the aged female mice had 26.55% lower LPP compared to younger mice. Vectorized Scale-Invariant Pattern Recognition (VIPR) analysis of the relative abundance of different tissue components revealed that the mid-urethra of old female mice contains less striated muscle, more extracellular matrix/fibrosis, and diminished elastin fibers ratio compared to young mice. Gene expression profiling analysis (bulk RNA-seq of the whole urethra) showed more down-regulated genes in aged than young mice. Immune response and muscle-related (striated and smooth) pathways were predominantly enriched. In contrast, keratinization, skin development, and cell differentiation pathways were significantly downregulated in aged urethral tissues compared to those from young female mice. These results suggest that molecular pathways (i.e., ACVR1/FST signaling and CTGF/TGF-β signaling) leading to a decreased striated muscle mass and an increase in fibrous extracellular matrix in the process of aging deserve further investigation for their roles in the declined urethral function.

Fibroblast growth factor (FGF) is a secreted ligand that is widely expressed in embryonic tissues but its expression decreases with age. In the developing prostate, FGF5 has been proposed to interact with the Hedgehog (Hh) signaling pathway to guide mitogenic processes. In the adult prostate, the FGF/FGFR signaling axis has been implicated in prostate carcinogenesis, but focused studies on FGF5 functions in the prostate are limited. Functional studies completed in other cancer models point towards FGF5 overexpression as an oncogenic driver associated with stemness, metastatic potential, proliferative capacity, and increased tumor grade. In this review, we explore the significance of FGF5 as a therapeutic target in prostate cancer (PCa) and other malignancies; and we introduce a potential route of investigation to link FGF5 to benign prostatic hyperplasia (BPH). PCa and BPH are two primary contributors to the disease burden of the aging male population and have severe implications on quality of life, psychological wellbeing, and survival. The development of new FGF5 inhibitors could potentially alleviate the health burden of PCa and BPH in the aging male population.

Prostate cancer is a health-threaten disease in men worldwide, however, lacking is the reliable biomarkers for patient management. Aberrant metabolic events including glucose metabolism are involved in prostate cancer progression. To examine the involvement of glucose metabolic pathways in prostate cancer, we analyzed the expression profiles of glucose transporter family genes using multiple RNA-seq datasets. Our results showed that three SLC2A family genes (SLC2A4/5/9) were significantly downregulated in primary prostate cancers compared to their benign compartments. These down-regulated expressions were inversely correlated with their gene promoter methylation and genome abnormalities. Among these three SLC2A genes, only SLC2A4 showed a significantly reverse correlation with all clinicopathological parameters, including TNM stage, disease relapse, Gleason score, disease-specific survival, and progression-free interval. In addition, the expression levels of these three genes were strongly correlated with anti-cancer immune cell filtration in primary prostate cancers. In a group of patients with early-onset prostate cancers, SLC2A4 also showed a strong negative correlation with multiple clinicopathological parameters, such as tumor mutation burden, biochemical relapse, pre-surgical PSA levels, and Gleason score but a positive correlation with progression-free interval after surgery. In metastatic castration-resistant prostate cancers (CRPC), SLC2A9 gene expression but not SLC2A4 or SLC2A5 genes showed a significant correlation with androgen receptor (AR) activity score and neuroendocrinal (NE) activity score. Meanwhile, SLC2A2/9/13 expression was significantly elevated in CRPC tumors with neuroendocrinal features compared to those without NE features. On the other hand, SLC2A10 and SlC2A12 gene expression were significantly reduced in NEPC tumors compared to CRPC tumors. Consistently, SLC2A10/12 expression levels were significantly reduced in castrated animals carrying the LuCaP35 xenograft models. Survival outcome analysis revealed that SLC2A4 expression in primary tumors is a favorable prognostic factor and SLC2A6 is a worse prognostic factor for disease-specific survival and progression-free survival in prostate cancer patients. In conclusion, our results suggest that SLC2A4/6 expressions are strong prognostic factors for prostate cancer progression and survival. The significance of SLC2A2/9/13 over-expression during NEPC progression needs more investigation.

Prostate cancer is the leading cause of cancer death after lung cancer in men. Recent studies showed that aberrant metabolic pathways are involved in prostate cancer development and progression. In this study, we performed a systemic analysis of glycolytic enzyme gene expression using the TCGA-PRAD RNAseq dataset. Our analysis revealed that among 25 genes, only four genes (HK2/GPI/PFKL/PGAM5) were significantly upregulated while nine genes (HK1/GCK/PFKM/PFKP/ALDOC/PGK1/PGAM1/ENO2/PKM) were downregulated in primary prostate cancer tissues compared to benign compartments. Among these 13 altered genes, four genes (ENO2/ALDOC/GPI/GCK) exhibited strong diagnostic potential in distinguishing malignant and benign tissues. Meanwhile, GPI expression exerted as a prognostic factor of progression-free and disease-specific survival. PFKL and PGAM5 gene expressions were associated with AR signaling scores in castration-resistant patients, and AR-targeted therapy suppressed their expression. In LuCap35 xenograft tumors, PFKL and PGAM5 expression was significantly reduced after animal castration, confirming the AR dependency. Conversely, GCK/PKLR genes were significantly associated with neuroendocrinal progression, representing two novel neuroendocrinal biomarkers for prostate cancer. In conclusion, our results suggest that GPI expression is a strong prognostic factor for prostate cancer progression and survival while GCK/PKLR are two novel biomarkers of prostate cancer progression to neuroendocrinal status.

Objective: Comparison of the clinical effectiveness and safety of three-dimensional transperitoneal laparoscopic radical prostatectomy (3D TLRP) versus 3D extraperitoneal LRP (3D ELRP) for prostate cancer.

Materials and methods: To retrospectively analyze the clinical and regular postoperative follow-up data of patients who underwent 3D LRP performed by the same attending surgeon at the Affiliated Hospital of Bengbu Medical College between 2017 and 2022. A total of 82 patients who met the criteria were included. They were divided into 3D TLRP (n = 39) and 3D ELRP groups (n = 43) according to the surgical approach. The preoperative, intraoperative, and postoperative data were compared.

Results: There were no statistically significant differences in preoperative characteristics between the two groups. There were also no statistically significant differences between the 3D TLRP and 3D ELRP groups in terms of intraoperative blood transfusion rate (12.82% vs. 2.33%), positive lymph node rate (11.11% vs. 2.38%), positive surgical margin rate (12.82% vs. 6.98%), pathological Gleason score, postoperative clinical stage, perioperative complication rate (10.26% vs. 4.65%), immediate urinary control rate (56.41% vs. 58.14%), 3-month postoperative urinary control rate (76.92% vs. 74.42%), 6-month postoperative urinary control rate (87.18% vs. 83.72%), 6-month postoperative biochemical recurrence rate (7.69% vs. 9.30%), or 6-month postoperative sexual function recovery rate (2.56% vs. 2.33%) (P > 0.05). Compared with the 3D ELRP group, the 3D TLRP group had a longer operative time (232.36 ± 48.52 min vs. 212.07 ± 41.76 min), more estimated blood loss (150.000 [100.0, 200.0] vs. 100.000 [100.0, 125.0]), longer recovery of gastrointestinal function (2.72 ± 0.89 vs. 2.26 ± 0.88), longer duration of drainage tube retention (5.69 ± 1.79 vs. 4.28 ± 2.68), and longer hospitalization time (12.54 ± 4.07 vs. 10.88 ± 2.97), with statistical significance (P < 0.05).

Conclusion: 3D TLRP and 3D ELRP have similar oncologic and functional outcomes. Clinically, physicians can choose a reasonable procedure according to the patient's specific situation and their own surgical experience.

Objective: Recent developments in bladder cancer treatment strategies have significantly improved the prognosis of clinically curable muscle invasive bladder cancer (MIBC) patients. Here, the prognostic factors of T2-4a, N0-x, M0 MIBC patients were investigated using the Surveillance, Epidemiology, and End Results (SEER) database and a novel nomogram model was established for prognosis prediction.

Methods: The data of 7,292 patients with T2-4a, N0-x, M0 MIBC were retrieved from the SEER database (2000-2020) and randomly classified into a training set (n = 5,106) and validation set (n = 2,188). Kaplan-Meier analysis was used to calculate cancer-specific survival (CSS) and overall survival (OS) rates of patients, and differences between survival curves were analyzed using the log-rank test. Cox regression analysis was used to screen and incorporate patient prognosis-affecting independent risk factors into the nomogram model. Consistency index (C-index) values and areas under the time-dependent receiver operating characteristic curve (AUC) were used to evaluate the discriminatory ability, and the calibration curve was used to assess the calibration of the model. Its predictive performance and American Joint Committee on Cancer (AJCC) stage were compared using decision curve analysis (DCA).

Results: The 1-, 3-, and 5-year CSS and OS rates of patients with T2-4a, N0-x, M0 MIBC were 76.9%, 56.0%, and 49.9%, respectively, and 71.3%, 47.9%, and 39.5%, respectively. Cox regression analysis showed that age, marital status, race, pathological type, tumor size, AJCC stage, T stage, N stage, surgery of primary tumor, regional lymph node dissection, radiation, and chemotherapy were independent prognostic risk factors of both CSS and OS (P < 0.05). The C-index and AUC of the nomogram model constructed based on the training and validation sets were both > 0.7, and calibration curves for predicting the 1-, 3-, and 5-year survival were consistent with the ideal curve. The nomogram model showed a higher net benefit with DCA than AJCC stage analysis.

Conclusion: The nomogram model could accurately predict the prognosis of patients with T2-4a, N0-x, M0 MIBC. It may help clinicians perform personalized prognosis evaluations and formulate treatment plans.

This study aimed to demonstrate the role of Zea mays or corn silk (CS) in the treatment of kidney stones after its proven effectiveness in folk medicine. Twenty-four rats were divided into four groups, the first represented the control group (negative control), and the second (positive control), was treated with 75% of ethylene glycol (EG) and 1% of ammonium chloride (AC) to induce stones in the kidneys of experimental animals. The animals of the third and fourth groups were treated with the same proportions of EG and AC, with the addition of extract of CS at a ratio of 200 and 400 mg/kg. After the 28^th day, the blood samples were taken from rats. All kidneys of rats from all groups were taken to histological examination. Another ten rats were divided into two groups and took the same time as the original experiment. Group E took a normal diet and served as negative control group whereas the group F took a normal diet with 500 mg/kg of CS to investigate the mechanism of CS as antiurolithiatic treatment. Blood samples were collected on the last day of the experiment to perform the required analyses. The rats were dissected and liver and kidney samples were taken to complete the histological study. The results showed a significant decrease in the CS group in plasma MDA, serum urea, and creatinine. Moreover, the histological study, in the CS rats group appeared to be fewer CaOx crystals. On the other hand, we observed a significant increase in urinary pH, urine volume urinary Mg, and citrate in-group E when compared with the F group. In conclusion, we infer that CS works as an antiurolithiatic drug by increasing urinary pH, diuresis, and its nephroprotective vims. So, we advise its use as an antiurolithiasis treatment but in its pharmaceutical forms.

Clear cell renal cell carcinoma is the most common subtype of renal cell carcinomas (RCCs) and accounts for 60%-70% of all RCCs cases in adults. Aberrations in the von Hippel-Lindau (VHL) gene on chromosome 3p occurred in > 90% of clear cell RCCs. Other tumor suppressor genes located on chromosome 3p, such as BAP1, PBRM1, and SETD2, also contribute to tumorigenesis. Clear cell RCCs with both BAP1 and VHL mutations may display distinctive histopathological features. Here, we report two cases of clear cell RCCs with BAP1 mutation. One tumor had VHL, BAP-1, and RAF1 mutations and the tumor nests and alveoli of tumor cells were surrounded by proliferative vessels and the optically clear cytoplasm contained numerous eosinophilic granules and hyaline globules of varying sizes. The other tumor had BAP1 and ATM mutations, and demonstrated clear cells with numerous eosinophilic granules and other typical histopathological features of conventional clear cell RCC. Furthermore, many tumor nodules with dense peripheral lymphocytic infiltrates contained rhabdoid cells. Sarcomatoid cells were also observed. Both tumor cells showed high-grade nuclei. Clear cell RCCs with BAP1 mutation exhibit aggressive clinical behaviors.