American journal of clinical and experimental urology最新文献

Purpose: Targeted prostate biopsies are increasingly being performed by urologists in the United States including those in the Pennsylvania Urologic Regional Collaborative, a physician-led data-sharing and quality improvement collaborative. To evaluate the performance of MRI guided fusion needle prostate biopsies in the collaborative, we analyzed the variability by practice in rates of detection of clinically significant prostate cancer and patient characteristics associated with detection of clinically significant prostate cancer.

Methods: We analyzed 857 first-time MRI fusion biopsy procedures performed at five practices (minimum 20 procedures) between 2015 and 2019. We used chi-square analysis for baseline patient characteristics and Grade Group (GG) ≥ 3 tumor detection rates by practice. Multivariable logistic regression was used to estimate the odds of clinically significant cancer detection when adjusting for baseline patient characteristics.

Results: Approximately 15% of men undergoing targeted MRI guided biopsy were ≤ 59 years old. Median prostate specific antigen (PSA) was 6.8 ng/ml. Detection rates for GG ≥ 3 tumors ranged from 14.3% to 28.3% (P = 0.02) across practices. However, the odds of GG ≥ 3 tumor detection did not differ significantly between practices after adjusting for clinical and radiographic factors. Overall, increased likelihood of detecting a GG ≥ 3 tumor was associated with increased age, DRE abnormalities, higher PSA, smaller gland volume and PI-RADS ≥ 4 MRI lesions. There was an 81% concordance rate between PI-RADS ≥ 4 and Gleason grade ≥ 3 prostate cancer.

Conclusion: We demonstrate the value of obtaining pre-biopsy MRI given high concordance between presence of suspicious lesions and MRI-targeted biopsy detection of clinically significant prostate cancer. Variability of baseline patient characteristics among practices may account for the observed differences in clinically significant cancer detection rates. These findings can aid standardization and quality improvement efforts within the collaborative.

Prostate cancer is the second leading cause of cancer-related deaths among men worldwide. With heavy androgen deprivation therapies, prostate cancer may shift to androgen receptor negative and neuroendocrine negative subtype of castration resistant prostate cancer, defined as double-negative prostate cancer. Double-negative prostate cancer is associated with poor prognosis and disease mortality. The molecular mechanisms underlying the emergence of double-negative prostate cancer remain poorly understood. Here, we demonstrate that Ubiquitin C-Terminal Hydrolase L1 (UCH-L1), is negatively correlated with androgen receptor levels in prostate cancer patients. UCH-L1 plays a functional role in tumorigenesis and metastasis in double-negative prostate cancer. Knock-down of UCH-L1 decreases double-negative prostate cancer colony formation in vitro and tumor growth in vivo. Moreover, decrease of UCH-L1 significantly delays cell migration in vitro and spontaneous metastasis and metastatic colonization in vivo. Proteomic analysis revealed that mTORC1 signaling, androgen response signaling and MYC targets are the top three decreased pathways upon UCH-L1 decrease. Further, treatment with LDN-57444, a UCH-L1 small molecule inhibitor, impairs double-negative prostate cancer cell colony formation, migration in vitro, and metastatic colonization in vivo. Our study reveals that UCH-L1 is an important regulator of double-negative prostate cancer tumor growth and progression, providing a promising therapeutic target for this subtype of metastatic prostate cancer.

Prophylactic antibiotics are commonly used to prevent infections and complications during surgeries. In this study inflammatory responses and infectious complications after utilizing antibiotic-loaded irrigation compared with intravenous (IV) prophylactic antibiotics. Eighty-eight participants with ureteral stones enrolled in this prospective randomized controlled trial. Participants were allocated into two groups, namely "standard" with 45 participants, and "antibiotic-loaded" with 43 participants. The "standard" group received standard normal saline irrigation with 1 gram of IV ceftriaxone 30 minutes before in transurethral ureterolithotripsy (TUL), while the "antibiotic-loaded" group received ceftriaxone-added irrigation fluid and did not receive any IV antibiotics. The laboratory tests, including Complete Blood Count (CBC), Erythrocyte Sedimentation Rate (ESR), C-reactive protein (CRP), venous blood gas (VBG), IL-6, creatinine, sodium, potassium, SIRS score, and urine culture were recorded. The continuous variables are described using either mean (standard deviation (SD)) or median (interquartile range (IQR)) and the t-test and Mann-Whitney test are used to infer them. The discrete variables are reported as numbers (percentages) and the Chi-squared test is applied to them. Statistical analyses were performed by the SPSS software (V.26, IBM) with a considering significance criterion of 0.05. Statistically differences were not found in postoperative inflammatory and infectious complications among the two groups (P>0.05) including SIRS score (P=0.385), WBC (P=0.589), IL-6 (P=0.365), ESR (P=0.171), CRP (P=0.279), Platelet (P=0.501), positive urine culture (P=0.922), and post-operative fever (P=0.162). Administering antibiotic-loaded irrigation fluid was as safe and effective as IV ceftriaxone in TUL and could be a reasonable alternative for IV antibiotics.

This case study emphasizes the critical role of accurate diagnosis and tailored management strategies in successfully treating bladder injuries, particularly in complex cases. We present a patient with trigonal involvement and a Grade V injury that did not respond to conservative treatment, underscoring the need for precise surgical management. However, considering the patient's condition and the variability in surgical approaches, a less invasive intervention was chosen, leading to successful management using an external catheter to allow the bladder to heal without direct contact with urine. This innovative approach resulted in complete recovery without surgery, demonstrating the potential for positive outcomes even in complex cases. The study reiterates the importance of prompt recognition and appropriate management to prevent adverse outcomes associated with bladder trauma, underscoring the significance of close clinical monitoring and individualized treatment strategies for successful outcomes.

Background: Genetic factors are thought to play a major role in erectile dysfunction (ED), but the search for specific ED-related genes remains a mysterious area characterised by limited and inconclusive research.

Methods: Whole blood expression quantitative trait loci (eQTLs) and the GWAS data related to the genetics of ED are derived from a Finnish database, Finngen, which contains a dataset of 1154 cases and 94024 controls, culminating in a total of 95178 individuals under scrutiny. Based on these pooled data, a Mendelian randomisation (MR) analysis of ED was performed. Subsequent analyses of PPI and single cell type expression help identify potential pathogenic genes, revealing the function of genes and their association with phenotypes.

Results: After SMR analysis, 110 ED-associated genes were screened, of which MDM4 Degree had the highest value with an OR of 1.8453076, was displaced on chromosome 1, and had a risk of promoting ED. Single-cell sequencing analysis results demonstrate the expression of the MDM4 gene in six cell types, further confirming the role of the MDM4 gene in ED.

Conclusions: Our study showed that among the 110 genes associated with ED, MDM4 was highly associated with an increased risk of ED. These findings strongly support personalised treatment strategies decision-making for ED patients.

Emphysematous pyelonephritis (EPN) is a rare infectious disease affecting the renal and perirenal tissues, wherein gas formation occurs in the renal parenchyma, perinephric tissues, or collecting systems. It can be life threatening with mortality rates upto 60%. Here, we report a case series of EPN during the COVID pandemic with COVID test-positive patients who were diagnosed based on clinical signs, symptoms, and CT scans. One patient was conservatively managed, one underwent nephrectomy, and the others were treated with percutaneous drainage and pigtailing. Despite being critically ill, all the patients recovered uneventfully. Owning to the rarity of the lesion and variations in the clinical spectrum, the diagnosis of EPN is challenging. EPN requires early diagnosis and prompt management. The interventional technique depends on the clinical status of the patient and the severity of the lesion. Although the threshold of intervention is low in normal clinical practice, in covid patients, we tried to manage patients conservatively and intervened only when unavoidable.

Histopathology, which is the gold-standard for prostate cancer diagnosis, faces significant challenges. With prostate cancer ranking among the most common cancers in the United States and worldwide, pathologists experience an increased number for prostate biopsies. At the same time, precise pathological assessment and classification are necessary for risk stratification and treatment decisions in prostate cancer care, adding to the challenge to pathologists. Recent advancement in digital pathology makes artificial intelligence and learning tools adopted in histopathology feasible. In this review, we introduce the concept of AI and its various techniques in the field of histopathology. We summarize the clinical applications of AI pathology for prostate cancer, including pathological diagnosis, grading, prognosis evaluation, and treatment options. We also discuss how AI applications can be integrated into the routine pathology workflow. With these rapid advancements, it is evident that AI applications in prostate cancer go beyond the initial goal of being tools for diagnosis and grading. Instead, pathologists can provide additional information to improve long-term patient outcomes by assessing detailed histopathologic features at pixel level using digital pathology and AI. Our review not only provides a comprehensive summary of the existing research but also offers insights for future advancements.

Background: Bladder cancer (BC) is very common among cancers of urinary system. It was usually categorized into two types: non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC). NMIBC and MIBC groupings are heterogeneous and have different characteristics.

Objectives: The study was aimed to find some hub genes and related signal pathways which might be engaged in the progression of BC and to investigate the relationship with clinical stages and its prognostic significance.

Methods: GSE37317 datasets were acquired from Gene Expression Omnibus (GEO) database. GEO2R on-line tool was selected to screen the differentially expressed genes (DEGs) of the two different types of BC. Then, Gene Ontology (GO) enrichment and KOBAS-Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of these DEGs were conducted. A protein-protein interaction (PPI) network was employed to help us screen hub genes and find significant modules. Finally, we made analysis of gene expression and survival curve by GEPIA and Kaplan-Meier plotter database.

Results: 224 DEGs were screened in total, with 110 showing increased expression and 114 demonstrating decreased expression. GO and KEGG pathway enrichment analysis showed that DEGs were mostly involved in collagen fibril organization, extracellular matrix (ECM) structural constituent, bHLH transcription factor binding, AGE-RAGE signaling pathway and TGF-beta signaling pathway. Only 3 hub genes (DCN, JUN, THBS1) displayed significantly higher expression compared to those in the healthy controls. These hub genes were also strongly related to clinical stages as well as overall survival (OS) of BC patients.

Conclusions: Taken together, most of hub genes involved in the progression of BC were related to ECM and EMT. In addition, 3 hub genes (DCN, JUN, THBS1) were strongly related with clinical stages and OS of BC patients. This study can enhance our comprehension of the progression of NMIBC and identify novel potential targets for MIBC.

Objectives: Prostate inflammation is linked to lower urinary tract dysfunction and is a key factor in chronic prostatitis/chronic pelvic pain syndrome. Autoimmunity was recently identified as a driver of prostate inflammation. Agonists of the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, have been used to suppress autoimmunity in mouse models of colitis, rhinitis, and dermatitis, but whether AHR agonists suppress prostate autoimmunity has not been examined. Here, we test whether ITE (2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester), an AHR agonist, suppresses inflammation, allodynia, and urinary dysfunction in a mouse model of experimental autoimmune prostatitis (EAP).

Methods: C57BL/6J adult male mice were immunized with rat prostate antigen to induce EAP or TiterMax Gold® adjuvant (uninflamed control). Mice were also treated with ITE (10 mg/kg/day IP) or DMSO (vehicle, 5 mg/kg/day IP) for 6 days. Using the Nanostring nCounter Inflammation Panel, we evaluated the impact of EAP and ITE on prostatic RNA abundance. We validated EAP and ITE-mediated changes in a subset of RNAs by RT-PCR and RNAScope in situ RNA detection.

Results: EAP appeared to heighten histological inflammation in the dorsal prostate, induced tactile allodynia, and appeared to increase the frequency of non-voiding bladder contractions. ITE mitigated some actions of EAP. EAP changed abundance of 40 inflammation-related RNAs, while ITE changed abundance of 28 inflammation-related RNAs. We identified a cluster of RNAs for which ITE protected against EAP-induced changes in the abundance of H2-Ab1, S100a8, and S100a9. ITE also increased the abundance of the AHR-responsive Cyp1a1 RNA.

Conclusions: These findings support the hypothesis that ITE activates the AHR in the prostate and reduces autoimmune-mediated prostatitis in mice.

Background: Testicular torsion is the major urologic emergency. If not treated promptly, this condition can result in testicular necrosis or long-term functional impairment. At present, there are few paper about long time follow-up of these patients. The primary objective of our study is to report the long-term clinical-instrumental data (mean follow-up 12 years) of patients treated for testicular torsion.

Methods: We considered patients treated for testicular torsion during the period between 1997 and 2017. Inclusion and exclusion criteria were created. Patients were contacted by phone between December 2021 and January 2022. Each patient underwent clinical and ultrasonographic evaluation, and in addition, some subjects were offered additional tests (hormonal assays and semen analysis).

Results: During the study period, 22 patients were treated for testicular torsion. From the ultrasonographic study, it was found that the volume of the affected testis is reduced and it is associated with microcalcifications and heterogeneous echogenicity. Morphovolumetric recovery seems to be more related to age of onset than to the degree of torsion.

Conclusions: Based on our results we can state that affected testes, if preserved, grow less and have altered ultrasonographic morphology. Clinically, the age of onset of torsion seems more important than the degree of torsion.