Patients with locally advanced and metastatic urothelial carcinoma have a low survival rate (median 15.7 months, 13.1-17.8), with only a 23% response rate to monotherapy treatment with anti-PDL1 ...checkpoint immunotherapy. To identify new therapeutic targets, we profiled the immune regulatory signatures during murine cancer development using the BBN carcinogen and identified an increase in the expression of the T cell inhibitory protein B7-H4 (VTCN1, B7S1, B7X). B7-H4 expression temporally correlated with decreased lymphocyte infiltration. While the increase in B7-H4 expression within the bladder by CD11b
+
monocytes is shared with human cancers, B7-H4 expression has not been previously identified in other murine cancer models. Higher expression of B7-H4 was associated with worse survival in muscle-invasive bladder cancer in humans, and increased B7-H4 expression was identified in luminal and luminal-papillary subtypes of bladder cancer. Evaluation of B7-H4 by single-cell RNA-Seq and immune mass cytometry of human bladder tumors found that B7-H4 is expressed in both the epithelium of urothelial carcinoma and CD68+ macrophages within the tumor. To investigate the function of B7-H4, treatment of human monocyte and T cell co-cultures with a B7-H4 blocking antibody resulted in enhanced IFN-γ secretion by CD4
+
and CD8
+
T cells. Additionally, anti-B7-H4 antibody treatment of BBN-carcinogen bladder cancers resulted in decreased tumor size, increased CD8
+
T cell infiltration within the bladder, and a complimentary decrease in tumor-infiltrating T regulatory cells (Tregs). Furthermore, treatment with a combination of anti-PD-1 and anti-B7-H4 antibodies resulted in a significant reduction in tumor stage, a reduction in tumor size, and an increased level of tumor necrosis. These findings suggest that antibodies targeting B7-H4 may be a viable strategy for bladder cancers unresponsive to PD-1 checkpoint inhibitors.
Lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) significantly impact quality of life among older men. Despite the prevalent use of the American Urological Association ...Symptom Index (AUA-SI) for BPH, this measure overlooks key symptoms such as pain and incontinence, underscoring the need for more comprehensive patient-reported outcome (PRO) tools. This study aims to integrate enhanced PROs into routine clinical practice to better capture the spectrum of LUTS, thereby improving clinical outcomes and patient care.
This prospective observational study will recruit men with LUTS secondary to BPH aged ≥ 50 years from urology clinics. Participants will be stratified into medical and surgical management groups, with PRO assessments scheduled at regular intervals to monitor LUTS and other health outcomes. The study will employ the LURN Symptom Index (SI)-29 alongside the traditional AUA-SI and other non-urologic PROs to evaluate a broad range of symptoms. Data on comorbidities, symptom severity, and treatment efficacy will be collected through a combination of electronic health records and PROs. Analyses will focus on the predictive power of these tools in relation to symptom trajectories and treatment responses. Aims are to: (1) integrate routine clinical tests with PRO assessment to enhance screening, diagnosis, and management of patients with BPH; (2) examine psychometric properties of the LURN SIs, including test-retest reliability and establishment of clinically meaningful differences; and (3) create care-coordination recommendations to facilitate management of persistent symptoms and common comorbidities measured by PROs.
By employing comprehensive PRO measures, this study expects to refine symptom assessment and enhance treatment monitoring, potentially leading to improved personalized care strategies. The integration of these tools into clinical settings could revolutionize the management of LUTS/BPH by providing more nuanced insights into patient experiences and outcomes. The findings could have significant implications for clinical practices, potentially leading to updates in clinical guidelines and better health management strategies for men with LUTS/BPH.
This study is registered in ClinicalTrials.gov (NCT05898932).
Prostatic abscess due to blastomycosis Sloan, Matthew J.; Manjee, Kiran G.; Kaplan, Leonard J. ...
Urology case reports,
05/2022, Letnik:
42
Journal Article
Recenzirano
Odprti dostop
Blastomycosis is an endemic infection caused by Blastomyces dermatitidis, found primarily in the southeastern, south-central, and Midwest United States. While the majority of infections typically ...present with pulmonary manifestations, they rarely present with symptoms isolated to the prostate. In order to better understand the clinical presentation, evaluation, and treatment of blastomycosis of the prostate, we present a 59-year-old male with urinary retention and lower urinary tract symptoms (LUTS).
Murine bladder tumor models are critical for the evaluation of new therapeutic options. Bladder tumors induced with the N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) carcinogen are advantageous over ...cell line-based models because they closely replicate the genomic profiles of human tumors, and, unlike cell models and xenografts, they provide a good opportunity for the study of immunotherapies. However, bladder tumor generation is heterogeneous; therefore, an accurate assessment of tumor burden is needed before randomization to experimental treatment. Described here is a BBN mouse model and protocol to evaluate bladder cancer tumor burden in vivo using a fast and reliable magnetic resonance (MR) sequence (true FISP). This method is simple and reliable because, unlike ultrasound, MR is operator-independent and allows for the straightforward post-acquisition image processing and review. Using axial images of the bladder, analysis of regions of interest along the bladder wall and tumor allow for the calculation of bladder wall and tumor area. This measurement correlates with ex vivo bladder weight (rs= 0.37, p = 0.009) and tumor stage (p = 0.0003). In conclusion, BBN generates heterogeneous tumors that are ideal for evaluation of immunotherapies, and MRI can quickly and reliably assess tumor burden prior to randomization to experimental treatment arms.
Current organizational guidelines regarding use of antibiotics during urinary tract catheterization are based on limited evidence and are not directly applicable to the pediatric urology population. ...We seek to improve understanding of this population by first evaluating current practices. This study aims to investigate practice patterns and attitudes of pediatric urologists regarding the use of antibiotics in the setting of urinary tract catheterization.
An online survey was sent to members of the Society for Pediatric Urology. Questionnaire sections included demographics, general questions about antibiotic use with catheterization, and specific clinical scenarios. Descriptive statistics were used, and chi-square analysis was performed to examine associations between demographics and specific responses.
Of 448 pediatric urologists surveyed, 154 (34%) responded to the survey. A majority of surveyed urologists (78%) prescribe daily prophylactic antibiotics with a hypospadias stent in place, but extensive variation in use of antibiotics was reported with other catheters and tubes. Extensive variation in practice patterns was also reported for three case scenarios regarding antibiotic prophylaxis with catheterization. Urologists > 50 years of age and fellowship-trained urologists were more likely to prescribe antibiotics for hypospadias stents (p = 0.02, p = 0.03), but no other significant associations between demographic characteristics and antibiotic use were found.
There is substantial variation in practice patterns among surveyed pediatric urologists regarding prophylactic antibiotic use with urinary catheterization. This variation, combined with a lack of objective data and increasing pressure to decrease infectious complications and combat antibiotic resistance, highlights the need for development of management guidelines for this unique population.
Objectives
To evaluate which of previously reported monogenic genes are associated with increased bladder cancer risk, we reviewed published papers on associations of genes and bladder cancer risk ...and performed a confirmation study of these genes in a large population‐based cohort.
Subjects and methods
A systematic review of published papers prior to June 2022 was performed first to identify all genes where germline mutations were associated with bladder cancer risk. The associations of these candidate genes with bladder cancer risk were then tested among 1695 bladder cancer cases and 186 271 controls in the UK Biobank (UKB). The robust SKAT‐O, a gene‐based analysis that properly controls for type I error rates due to unbalanced case–control ratio, was used for association tests adjusting for age at recruitment, gender, smoking status, and genetic background.
Results
The systematic review identified nine genes that were significantly associated with bladder cancer risk in at least one study (p < 0.05), including MUTYH, MSH2, MSH6, MLH1, ATM, BRCA2, ERCC5, TGFB1 and CHEK2. When pathogenic/likely pathogenic mutations were aggregated within each gene, the association was confirmed for three genes in the UKB at p < 0.0056 (Bonferroni correction for nine tests), including CHEK2, ATM and BRCA2, all also known to be associated with hereditary breast cancer. Suggestive evidence of association was found for two other genes, including MLH1 (p = 0.006) and MSH2 (p = 0.007), both known to be associated with Lynch syndrome. Among these five genes, the bladder cancer risks range from 1.60 (ATM) to 4.88 (MLH1), and mutation carrier rates in cases range from 0.06% (MSH2) to 2.01% (CHEK2).
Conclusion
This study provides statistical evidence for association of previously reported genes and bladder cancer risk and has clinical utility for risk assessment and genetic counselling.
Bladder cancer is initially diagnosed and staged with a transurethral resection of bladder tumor (TURBT). Patient survival is dependent on appropriate sampling of layers of the bladder, but pathology ...reports are dictated as free text, making large-scale data extraction for quality improvement challenging. We sought to automate extraction of stage, grade, and quality information from TURBT pathology reports using natural language processing (NLP).
Patients undergoing TURBT were retrospectively identified using the Northwestern Enterprise Data Warehouse. An NLP algorithm was then created to extract information from free-text pathology reports and was iteratively improved using a training set of manually reviewed TURBTs. NLP accuracy was then validated using another set of manually reviewed TURBTs, and reliability was calculated using Cohen's κ.
Of 3,042 TURBTs identified from 2006 to 2016, 39% were classified as benign, 35% as Ta, 11% as T1, 4% as T2, and 10% as isolated carcinoma in situ. Of 500 randomly selected manually reviewed TURBTs, NLP correctly staged 88% of specimens (κ = 0.82; 95% CI, 0.78 to 0.86). Of 272 manually reviewed T1 tumors, NLP correctly categorized grade in 100% of tumors (κ = 1), correctly categorized if muscularis propria was reported by the pathologist in 98% of tumors (κ = 0.81; 95% CI, 0.62 to 0.99), and correctly categorized if muscularis propria was present or absent in the resection specimen in 82% of tumors (κ = 0.62; 95% CI, 0.55 to 0.73). Discrepancy analysis revealed pathologist notes and deeper resection specimens as frequent reasons for NLP misclassifications.
We developed an NLP algorithm that demonstrates a high degree of reliability in extracting stage, grade, and presence of muscularis propria from TURBT pathology reports. Future iterations can continue to improve performance, but automated extraction of oncologic information is promising in improving quality and assisting physicians in delivery of care.
The AUA guidelines for benign prostatic hyperplasia distinguish treatments based upon prostate volume (PV), particularly for very large prostates (> 150 mL). While the clinical outcomes and benefits ...of Aquablation have been studied for men with average and large prostates, it is unknown whether this technology can be used for very large prostates.
Men with PV > 150 mL undergoing Aquablation were identified retrospectively from four North American hospitals. The surgical times and clinical outcomes of men with very large prostates (> 150 mL) were compared to data from men with average PV ≤ 80 mL (WATER study) and large PV 80 mL-150 mL (WATER II study).
The average PV of men who underwent Aquablation with very large prostates was 209 mL ± 56 (n = 34, range 151-362 mL), large PV 107 mL ± 20 (n = 101, range 80-150 mL) and average PV 54 mL ± 16 (n = 116, range 30-80 mL). For men with PV > 150 mL, baseline IPSS was 19 ± 6. With a mean follow up of 7 ± 9 months, the IPSS improved to 7 ± 5 (p < 0.001). Peak urinary flow rate, Qmax, improved from 7 ± 4 mL/s to 19 ± 5 mL/s (p<0.001). Compared to the two other PV groups, there were no differences in terms of improvements in IPSS, quality of life, or uroflowmetry. There were no reports of transfusions (0%) in the cohort of men with very large prostates.
In the present study, we demonstrate that Aquablation is effective and safe in prostates greater than 150 mL while showing consistent outcomes compared to average and large prostates sizes.
Aquablation has been well-studied in prostates sizes up to 150 mL. Recently, American Urological Association guidelines distinguish surgical interventions for men with large prostates (80 mL-150 mL) ...and now very large prostates (> 150 mL). Readers will gain an understanding of how to use Aquablation in the very large prostate size category.
Transrectal ultrasound-guided prostate needle biopsy (PB) is considered the gold standard for the diagnosis of prostate cancer. Recently, lower urinary tract symptoms and erectile dysfunction have ...been reported following PB. We reviewed the literature on PB and these symptoms and summarized known findings between these conditions and other variables, such as periprostatic nerve block, saturation biopsy, serial biopsies, and psychological factors associated with PB and cancer. A PubMed search was performed using keywords “prostate biopsy,” “complications,” “erectile dysfunction,” “lower urinary tract symptoms,” “anxiety,” and “quality of life.” Eleven key papers are discussed and personal experience is drawn upon. Based upon available evidence, PB appears to be associated with short-term exacerbation of urinary symptoms in some men, as well as associated with anxiety and temporary erectile dysfunction, without a distinct relationship to periprostatic nerve block or the number of cores biopsied. Additional studies are warranted to determine the definitive etiology of these symptoms and to determine if interventions could reduce patient morbidity. In the interim, patients should be educated and counseled about these risks before undergoing PB.
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