American journal of clinical and experimental urology最新文献

Prostate cancer is one of the most common cancers in men. Despite the development of diverse therapeutic agents for different types and stages, the progression or spread of the disease is inevitable. Another problem is the development of resistance of cancer cells to available therapeutics. Therefore, additional medicaments are urgently needed. Resveratrol is a polyphenolic phytoalexin found in numerous plants and fruits like red grapes or blueberries. Resveratrol possesses antiproliferative, anti-angiogenic and anticancer activities well proven in different types of cancer including prostate cancer. To date, it is not used clinically due to poor solubility, low bioavailability, and other limiting factors. In order to overcome these limitations, novel nanoparticle-based formulations were developed over the past years. In this review article, studies about the effect of resveratrol on prostate cancer cells are discussed focusing especially on those studies using nanotechnology. An electronic literature research was performed utilizing PubMed in August 2022. Scientific publications, which examine resveratrol using nanotechnology, are discussed. The studies clearly indicate that resveratrol-loaded nanoparticles exhibited a remarkable anti-cancer activity in various hormone-sensitive and hormone-insensitive prostate cancer cell lines including docetaxel-resistant prostate-cancer cells. The types of nanoparticles that were used varied and influenced the outcome. Additionally, the meaning of the surface functionality of the nanoparticles is emphasized. No reduction of the anti-proliferative activity of resveratrol was shown when used encapsulated. Additionally, synergistic effects of resveratrol and docetaxel were proven. Resveratrol-loaded nanoparticles, especially when combined, may represent the next generation of anticancer substances. However, further in vivo/clinical studies are necessary to confirm their clinical effectiveness.

Objective: Since the advent of the Mulcahy technique of three-piece inflatable penile prosthesis (IPP) salvage, there have been multiple iterations of salvage prosthesis procedures reported in the literature. All of these techniques employ traditional antibiotic irrigation with or without rechanneling. We present our technique of salvage IPP using 0.05% chlorhexidine gluconate (Irrisept^®) with corporal rechanneling for length preservation.

Materials and methods: Our technique of IPP salvage begins with access via a 5 cm vertical midline scrotal incision. Dissection down to the corpora is performed with a combination of blunt dissection and dissection with fine tipped Metzenbaum scissors. Each component of the prior IPP is sequentially removed starting with the cylinders, followed by the pump, and finally the reservoir. Irrisept^® is used to copiously irrigate out both cavernosal bodies as well as the scrotal compartment and prior reservoir location. A two minute dwell time of the Irrisept^® is employed after mechanical irrigation. A penrose drain is placed from the space of Retzius through a separate stab incision in the scrotum. Corporotomies are closed, followed by Dartos fascia and scrotal skin. A complete change in gown and gloves of all members of the surgical team and a new set of drapes and instruments is performed. Through a separate subcoronal incision, two new corporotomies are made and separate channels created using nine inch Metzenbaum scissors. These channels are irrigated with Irrisept^®. A 9 mm malleable penile prosthesis (MPP) is inserted and corporotomies and skin incision are closed.

Results: A total of four men with prior penoscrotal IPP placement underwent salvage IPP with MPP from January 2022 to October 2022. Median operative time was 165 minutes. Median preoperative cylinder size was 23.5 cm. Median postoperative malleable cylinder size was 23 cm. Median length of follow up was 4.8 months. There were no cases of MPP erosion or infection. Two patients elected to undergo repeat IPP insertion after 6 months with same cylinder size.

Conclusion: IPP salvage with chlorhexidine irrigation and soak as well as separate corporal channeling in a noninfected field for MPP insertion is a viable strategy for infected prostheses given the ease of performance, low risk of repeat infection of the malleable device, and maintenance of corporal length of any subsequent prostheses.

Introduction: Kidney stone matrix proteins may help explain cellular mechanisms of stone genesis. However, most existing proteomic studies have focused on calcium oxalate stones. Here, we present a comparative proteomic analysis of different kidney stone types.

Methods: Proteins were extracted from the stones of patients undergoing percutaneous nephrolithotomy (PCNL). Approximately 20 μg of protein was digested into tryptic peptides using filter aided sample preparation, followed by liquid chromatography tandem-mass-spectrometry using an EASY-nLC 1200 and Orbitrap Fusion Lumos mass spectrometer. A standard false discovery rate cutoff of 1% was used for protein identification. Stone analysis was used to organize stone samples into similar groups. We selected the top 5% of proteins based on total ion intensities and used DAVID and Ingenuity Pathway Analysis to identify and compare significantly enriched gene ontologies and pathways between groups.

Results: Six specimens were included and organized into the following four groups: 1) mixed uric acid (UA) and calcium-based, 2) pure UA, 3) pure ammonium acid urate (AAU), and 4) pure calcium-based. We identified 2,426 unique proteins (1,310-1,699 per sample), with 11-16 significantly enriched KEGG pathways identified per group and compared via heatmap. Based on number of unique proteins identified, this is the deepest proteomic study of kidney stones to date and the first such study of an AAU stone.

Conclusions: The results indicate that mixed UA and calcium-based kidney stones are more similar to pure UA stones than pure calcium-based stones. AAU stones appear more similar to pure calcium-based stones than UA containing stones and may be related to parasitic infections. Further research with larger cohorts and histopathologic correlation is warranted.

Extramural venous invasion (EMVI) recognized on magnetic resonance imaging (MRI) is an unequivocal biomarker for detecting adverse outcomes in rectal cancer: however it has not yet been explored in the area of bladder cancer. In this study, we assessed the feasibility of identifying EMVI findings on MRI in patients with bladder cancer and its avail in identifying adverse pathology. In this single-institution retrospective study, the MRI findings inclusive of EMVI was described in patients with bladder cancer that had available imaging between January 2018 and June 2020. Patient demographic and clinical information were retrieved from our electronic medical records system. Histopathologic features frequently associated with poor outcomes including lymphovascular invasion (LVI), variant histology, muscle invasive bladder cancer (MIBC), and extravesical disease (EV) were compared to MRI-EMVI. A total of 38 patients were enrolled in the study, with a median age of 73 years (range 50-101), 76% were male and 23% were females. EMVI was identified in 23 (62%) patients. There was a significant association between EMVI and MIBC (OR = 5.30, CI = 1.11-25.36; P = 0.036), and extravesical disease (OR = 17.77, CI = 2.37-133; P = 0.005). We found a higher probability of presence of LVI and histologic variant in patients with EMVI. EMVI had a sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) of 90%, 73%, 94% and 63% respectively in detecting extravesical disease. Our study suggests, EMVI may be a useful biomarker in bladder cancer imaging, is associated with adverse pathology, and could be potentially integrated in the standard of care with regards to MRI reporting systems. A larger study sample size is further warranted to assess feasibility and applicability.

Background: Nocturnal enuresis is a common problem in children and could be treated with desmopressin therapy. Here we assessed ultrasound indices affecting disease severity and treatment responses in candidates for pharmacotherapy for nocturnal enuresis.

Methods: This prospective study was conducted in 2021-2022 on children diagnosed with nocturnal enuresis and candidates for desmopressin therapy. Demographic data of patients including age and gender were collected by a checklist. The severity of the disease was categorized into mild, moderate and severe. We measured the bladder volume index (BVI), bladder wall thickness (BT) and bladder volume wall thickness index (BVWI) by ultrasound. Patients were treated with desmopressin (administered 120 µg, stat and before sleeping) for 4 months and treatment responses were determined and compared.

Results: In this study, data from 72 patients were analyzed. Complete response was achieved in 16 patients (22.2%), 25 patients (34.7%) had a good response to treatments, 18 patients (25%) had a partial response and 13 patients (18.1%) had no response. There was a significantly positive correlation between low and normal BVWI and the severity of the disease. Normal BVWI was found mostly in children with a mild degree of nocturnal enuresis; while low BVWI was associated with severe cases. There was a significant inverse correlation between response to treatment and bladder wall thickness. BVWI was significantly correlated with response to treatment. It was shown that 81.3% of children with complete responses and 76% of children with good responses had a normal BVWI, while 76.9% of children who showed no response to treatment had a low BVWI.

Conclusion: BVWI and bladder wall thickness were significantly correlated with treatment response and BVWI had significant correlations with disease severity.

Benign prostate hyperplasia and prostate cancer are common diseases that involve the overgrowth of prostatic tissue. Although their pathologies and symptoms differ, both diseases show aberrant activation of prostate progenitor cell phenotypes in a tissue that should be relatively quiescent. This phenomenon prompts a need to better define the normal prostate progenitor cell phenotype and pursue the discovery of causal networks that could yield druggable targets to combat hyperplastic prostate diseases. We used single-cell (sc) RNA-Seq analysis to confirm the identity of a luminal progenitor cell population in both the hormonally intact and castrated mouse prostate. Using marker genes from our scRNA-Seq analysis, we identified factors necessary for the regeneration phenotype of prostate organoids derived from mice and humans in vitro. These data outline potential factors necessary for prostate regeneration and utilization of scRNA-Seq approaches for the identification of pharmacologic strategies targeting critical cell populations that drive prostate disease.

Genitourinary development is a delicately orchestrated process that begins in the embryo. Once complete, the genitourinary system is a collection of functionally disparate organs spread throughout the abdominal and pelvic regions. These distinct organs are interconnected through an elaborate duct system which aggregates the organs' products to a common exit point. The complicated nature of the genitourinary system makes it highly susceptible to developmental disruptions that produce anomalies. In fact, genitourinary anomalies are among the most common class of human birth defects. Aside from congenital anomalies of the kidney and urinary tract (CAKUT), for males, these birth defects can also occur in the penis (hypospadias) and testis (cryptorchism), which impact male fertility and male mental health. As genetic technology has advanced, it has become clear that a subset of cases of genitourinary birth defects are due to gene variation causing dosage changes in critical regulatory genes. Here we first review the parallels between human and mouse genitourinary development. We then demonstrate how translational research leverages mouse models of human gene variation cases to advance mechanistic understanding of causation in genitourinary birth defects. We close with a view to the future highlighting upcoming technologies that will provide a deeper understanding of gene variation affecting regulation of genitourinary development, which should ultimately advance treatment options for patients.

Functional loss of the two major tumor repressors, TP53 and RB1, is frequently involved in the emergence and progression of castration-resistant prostate cancer (CRPC). Inactivating mutations in TP53 and RB1 promote lineage variants that suppress the androgen receptor axis and enhance therapy resistance. The present study provides the first evidence that RB1 loss, and not TP53 loss, is sufficient to activate the master regulator transcription factor ONECUT2 (OC2) in mCRPC. OC2 upregulation is common in CRPC and drives metastasis and lineage plasticity, particularly neuroendocrine differentiation, in model systems. Pharmacologic inhibition of OC2 was reported to suppress established human CRPC metastases in mice. Here we show that RB1 silencing in human and mouse prostate cancer models is sufficient to upregulate OC2, at least in part through epigenetic regulation. OC2 expression downregulated TP53 transcription and inactivated RB1 via phosphorylation. OC2 expression and activation in human CRPC correlated with bi- or single-allelic loss of RB1 and inversely with RB1 expression and activity. A small molecule OC2 inhibitor blocked enzalutamide-induced lineage plasticity in vitro. These findings indicate that activation of OC2 in CRPC occurs in response to RB1 inactivation, and that biomarkers of RB1 activity may be useful for stratifying patients refractory to hormone therapy where OC2 is targeted pharmacologically.

Background: Prostatic inflammation is closely linked to the development and progression of benign prostatic hyperplasia (BPH). Clinical studies of non-steroidal anti-inflammatory drugs, which inhibit cyclooxygenase-2 (COX-2), targeting prostate inflammation patients with symptomatic BPH have demonstrated conflicting results, with some studies demonstrating symptom improvement and others showing no impact. Thus, understanding the role of the cyclooxygenases in BPH and prostatic inflammation is important.

Methods: The expression of COX-1 was analyzed in a cohort of donors and BPH patients by immunohistochemistry and compared to previously determined characteristics for this same cohort. The impact of mitochondrial dysfunction on COX-1 and COX-2 was determined in experiments treating human benign prostate epithelial cell lines BPH-1 and RWPE-1 with rotenone and MitoQ. RWPE-1 cells were transfected with small interfering RNA specific to complex 1 gene NDUFS3.

Results: COX-1 expression was increased in the epithelial cells of BPH specimens compared to young healthy organ donor and normal prostate adjacent to BPH and frequently co-occurred with COX-2 alteration in BPH patients. COX-1 immunostaining was associated with the presence of CD8+ cytotoxic T-cells, but was not associated with age, prostate size, COX-2 or the presence of CD4+, CD20+ or CD68+ inflammatory cells. In cell line studies, COX protein levels were elevated following treatment with inhibitors of mitochondrial function. MitoQ significantly decreased mitochondrial membrane potential in RWPE-1 cells. Knockdown of NDUFS3 stimulated COX-1 expression.

Conclusion: Our findings suggest COX-1 is elevated in BPH epithelial cells and is associated with increased presence of CD8+ cytotoxic T-cells. COX-1 can be induced in benign prostate epithelial cells in response to mitochondrial complex I inhibition, and knockdown of the complex 1 protein NDUFS3. COX-1 and mitochondrial dysfunction may play more of a role than previously recognized in the development of age-related benign prostatic disease.

Objectives: Thrombosis is a major cause of early allograft loss in renal transplantation. Herein, we assessed the frequency of acute graft thrombosis in patients who underwent renal transplant and received anticoagulant or antiplatelet agents.

Methods: We performed a systematic review of all available case series studies of anticoagulant and/or antiplatelet prophylaxis of thrombosis in renal transplantation. The data were pooled in a proportional meta-analysis.

Results: Twenty-one case series were identified from 7,160 retrieved titles. A total of 3,246 patients were analyzed (1,718 treated with antiplatelet and/or anticoagulant agents and 1,528 non-treated control subjects). Allograft thrombosis occurred in 7.24% (95% CI 3.45 to 12.27%) of the patients receiving no intervention compared with 3.38% (95% CI 1.45 to 6.1%), 1.2% (95% CI 0.6 to 2.1%) and 0.47% (95% CI 0.001 to 1.79%) of the patients in the anticoagulant, aspirin, and aspirin + anticoagulant groups, respectively. The bleeding complication rate for anticoagulants was significantly higher than in the other groups.

Conclusions: Our data suggests that anticoagulants, and aspirin, either alone or in association with an anticoagulant, seem to have a low frequency of acute allograft thrombosis after kidney transplantation. Higher hemorrhagic complication rates might occur when anticoagulants are used.