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HER2, encoded by the ERBB2 gene, is an important druggable driver of human cancer gaining increasing importance as a therapeutic target in urothelial carcinoma (UC). The genomic underpinnings of HER2 overexpression in ERBB2 nonamplified UC are poorly defined. To address this knowledge gap, we investigated 172 UC tumors from patients treated at the University of California San Francisco, using immunohistochemistry and next-generation sequencing. We found that GATA3 and PPARG copy number gains individually predicted HER2 protein expression independently of ERBB2 amplification. To validate these findings, we interrogated the Memorial Sloan Kettering/The Cancer Genome Atlas (MSK/TCGA) dataset and found that GATA3 and PPARG copy number gains individually predicted ERBB2 mRNA expression independently of ERBB2 amplification. Our findings reveal a potential link between the luminal marker HER2 and the key transcription factors GATA3 and PPARG in UC and highlight the utility of examining GATA3 and PPARG copy number states to identify UC tumors that overexpress HER2 in the absence of ERBB2 amplification. In summary, we found that an increase in copy number of GATA3 and PPARG was independently associated with higher ERBB2 expression in patient samples of UC. This finding provides a potential explanation for HER2 overexpression in UC tumors without ERBB2 amplification and a way to identify these tumors for HER2-targeted therapies.

Exposure to ambient air pollution has significant adverse health effects; however, whether air pollution is associated with urological cancer is largely unknown. We conduct a systematic review and meta-analysis with epidemiological studies, showing that a 5 μg/m3 increase in PM2.5 exposure is associated with a 6%, 7%, and 9%, increased risk of overall urological, bladder, and kidney cancer, respectively; and a 10 μg/m3 increase in NO2 is linked to a 3%, 4%, and 4% higher risk of overall urological, bladder, and prostate cancer, respectively. Were these associations to reflect causal relationships, lowering PM2.5 levels to 5.8 μg/m3 could reduce the age-standardized rate of urological cancer by 1.5 ~ 27/100,000 across the 15 countries with the highest PM2.5 level from the top 30 countries with the highest urological cancer burden. Implementing global health policies that can improve air quality could potentially reduce the risk of urologic cancer and alleviate its burden.

WHAT IS THIS SUMMARY ABOUT?: This summary provides the results of a study of two treatments for cancer, enfortumab vedotin and pembrolizumab, that were studied together against locally advanced or metastatic urothelial cancer (la/mUC), a cancer that occurs most commonly in the bladder. WHAT WERE THE RESULTS?: In the 45 patients studied, around 16% did have serious side effects, but most side effects were manageable. Twenty-four percent of patients, however, stopped the study treatment because of their side effects. Within about 2 months of starting treatment, most patients (73%) tumors were smaller and stayed smaller, on average, for more than 2 years. WHAT DO THE RESULTS MEAN?: The combination of enfortumab vedotin plus pembrolizumab is a new treatment option for patients with locally advanced or metastatic urothelial cancer when they cannot receive the typical treatment, cisplatin. Advanced or metastatic urothelial cancer is a type of cancer where the cancer has already spread outside of the bladder or urinary tract.

Compared to a Western diet, the Mediterranean diet moves away from red meat and processed foods. Universally regarded as a healthier dietary alternative, the Mediterranean diet has garnered scientific endorsement for its ability to confer an array of compelling benefits. These health benefits encompass not only a lowered incidence of Type 2 diabetes with a reduction in obesity, but also a robust protective effect on cardiovascular health. Extensive literature exists to corroborate these health benefits; however, the impact of a Mediterranean diet on urologic diseases, specifically sexual dysfunction, lower urinary tract symptoms, stone disease, and urologic cancers are not well studied. Understanding how dietary habits may impact these urologic conditions can contribute to improved prevention and treatment strategies.A total of 955 papers from PubMed and Embase were systematically reviewed and screened. After exclusion of disqualified and duplicated studies, 58 studies consisting of randomized controlled trials, cohort studies, cross sectional studies, reviews and other meta-analyses were included in this review. 11 primary studies were related to the impact of a Mediterranean diet on sexual dysfunction, 9 primary studies regarding urinary symptoms, 8 primary studies regarding stone disease, and 9 primary studies regarding urologic cancers. All primary studies included were considered of good quality based on a New-Castle Ottawa scale. The results demonstrate a Mediterranean diet as an effective means to prevent as well as improve erectile dysfunction, nephrolithiasis, lower urinary tract symptoms, and urinary incontinence. The review highlights the need for additional research to study the impact of diet on urologic cancers and other urologic conditions such as premature ejaculation, loss of libido, female sexual dysfunction, and overactive bladder.

AimsPre-surgical risk classification tools for prostate cancer have shown better patient stratification with the addition of cribriform pattern 4 (CC) and intraductal prostatic carcinoma (IDC) identified in biopsies. Here, we analyse the additional prognostic impact of CC/IDC observed in prostatectomies using Cancer of Prostate Risk Assessment post-surgical (CAPRA-S) stratification.MethodsA retrospective cohort of treatment-naïve radical prostatectomy specimens from three North American academic institutions (2010-2018) was assessed for the presence of CC/IDC. Patients were classified, after calculating the CAPRA-S scores, into low-risk (0-2), intermediate-risk (3-5) and high-risk (6-12) groups. Kaplan-Meier curves were created to estimate biochemical recurrence (BCR)-free survival. Prognostic performance was examined using Harrell's concordance index, and the effects of CC/IDC within each risk group were evaluated using the Cox proportional hazards models.ResultsOur cohort included 825 prostatectomies (grade group (GG)1, n=94; GG2, n=475; GG3, n=185; GG4, n=13; GG5, n=58). CC/IDC was present in 341 (41%) prostatectomies. With a median follow-up of 4.2 years (range 2.9-6.4), 166 (20%) patients experienced BCR. The CAPRA-S low-risk, intermediate-risk and high-risk groups comprised 357 (43%), 328 (40%) and 140 (17%) patients, and discriminated for BCR-free survival (p

PURPOSE: Clinical trials are valuable evidence for managing urologic malignancies. Early termination of clinical trials is associated with a waste of resources and may substantially affect patient care. We sought to study the termination rate of urologic cancer clinical trials and identify factors associated with trial termination. METHODS: A cross-sectional search of ClinicalTrials.gov identified completed and terminated kidney, prostate, and bladder cancer clinical trials started. Trials were assessed for reasons for termination. Multivariable analyses were conducted to determine the significant factors associated with the termination. RESULTS: Between 2000 and 2020, 9,145 oncology clinical trials were conducted, of which 11.30% (n = 1,033) were urologic cancer clinical trials. Of the urologic cancer clinical trials, 25.38% (n = 265) were terminated, with low patient accrual being the most common reason for termination, 52.9% (n = 127). Multivariable analysis showed that only the university funding source odds ratio (OR) of 2.20 (95% CI, 1.45 to 3.32), single-center studies OR of 2.11 (95% CI, 1.59 to 2.81), and sample size of

Unilateral Nephrectomy is one of the most common treatments for surgical diseases of the kidney but often results in postsurgical acute kidney injury (AKI). In the current study, we aimed to investigate the risk factors for AKI in patients who have received Unilateral Nephrectomy. We retrospectively analysed 528 patients who underwent Unilateral Nephrectomy for different etiologies between January 2013 and December 2018 at the Affiliated Hospital of Qingdao University. We recorded the prevalence and severity of AKI, age, gender, diabetes, body mass index (BMI), hypertension, preoperative renal function, etiology, performed surgically, anaemia, albumin, coagulation, lactate dehydrogenase, nitrogen (BUN), and uric acid. Univariate and multivariate logistic regression analyses were used to investigate the predictors of AKI in patients with Unilateral Nephrectomy. Overall, 218 of the 528 patients (41.2%) developed AKI during their hospitalisation. Univariate analysis showed that AKI was significantly associated with gender (male, OR = 1.866, P = 0.001), overweight (OR = 2.19, P = 0.0002), and surgical approach (OR = 1.7, P = 0.018), while multivariate logistic regression analysis showed that male gender (OR = 1.953, P = 0.001), overweight (OR = 2.176, P = 0.001), and preoperative renal function (OR = 0.507, P = 0.001) were independent factors for AKI. Regression analysis among different etiologies showed significant differences in postoperative AKI. After Unilateral nephrectomy, AKI is more likely to occur in overweight male patients with normal kidney function. AKI occurred more frequently in patients who are kidney donors, but rarely in those with non-function kidneys. [ABSTRACT FROM AUTHOR]

Abstract Unilateral Nephrectomy is one of the most common treatments for surgical diseases of the kidney but often results in postsurgical acute kidney injury (AKI). In the current study, we aimed to investigate the risk factors for AKI in patients who have received Unilateral Nephrectomy. We retrospectively analysed 528 patients who underwent Unilateral Nephrectomy for different etiologies between January 2013 and December 2018 at the Affiliated Hospital of Qingdao University. We recorded the prevalence and severity of AKI, age, gender, diabetes, body mass index (BMI), hypertension, preoperative renal function, etiology, performed surgically, anaemia, albumin, coagulation, lactate dehydrogenase, nitrogen (BUN), and uric acid. Univariate and multivariate logistic regression analyses were used to investigate the predictors of AKI in patients with Unilateral Nephrectomy. Overall, 218 of the 528 patients (41.2%) developed AKI during their hospitalisation. Univariate analysis showed that AKI was significantly associated with gender (male, OR = 1.866, P = 0.001), overweight (OR = 2.19, P = 0.0002), and surgical approach (OR = 1.7, P = 0.018), while multivariate logistic regression analysis showed that male gender (OR = 1.953, P = 0.001), overweight (OR = 2.176, P = 0.001), and preoperative renal function (OR = 0.507, P = 0.001) were independent factors for AKI. Regression analysis among different etiologies showed significant differences in postoperative AKI. After Unilateral nephrectomy, AKI is more likely to occur in overweight male patients with normal kidney function. AKI occurred more frequently in patients who are kidney donors, but rarely in those with non-function kidneys.

Background Bladder cancer is characterized by frequent mutations, which provide potential therapeutic targets for most patients. The effectiveness of emerging personalized therapies depends on an accurate molecular diagnosis, for which the accurate estimation of the neoplastic cell percentage (NCP) is a crucial initial step. However, the established method for determining the NCP, manual counting by a pathologist, is time-consuming and not easily executable. Methods To address this, artificial intelligence (AI) models were developed to estimate the NCP using nine convolutional neural networks and the scanned images of 39 cases of urinary tract cancer. The performance of the AI models was compared to that of six pathologists for 119 cases in the validation cohort. The ground truth value was obtained through multiplexed immunofluorescence. The AI model was then applied to 41 cases in the application cohort that underwent next-generation sequencing testing, and its impact on the copy number variation (CNV) was analyzed. Results Each AI model demonstrated high reliability, with intraclass correlation coefficients (ICCs) ranging from 0.82 to 0.88. These values were comparable or better to those of pathologists, whose ICCs ranged from 0.78 to 0.91 in urothelial carcinoma cases, both with and without divergent differentiation/ subtypes. After applying AI-driven NCP, 190 CNV (24.2%) were reclassified with 66 (8.4%) and 78 (9.9%) moved to amplification and loss, respectively, from neutral/minor CNV. The neutral/minor CNV proportion decreased by 6%. Conclusions These results suggest that AI models could assist human pathologists in repetitive and cumbersome NCP calculations.

Objectives To evaluate the clinical value of the Paris system for reporting urinary cytology (TPS) in the diagnosis of urothelial carcinoma (UC). Methods A total of 1 744 cytological diagnostic records (from 751 cases) were collected retrospectively. All specimens were voided urines and histopathology as the gold standard. The sensitivity and specificity of urinary cytological diagnosis of UC and risk of high grade malignant (ROHM) in each diagnostic category were compared. Results There were 360 cases with histopathology. The percentage of negative for high-grade urothelial carcinoma (NHGUC) was 30.1% (226/751), atypical urothelial cells (AUC) was 29.8% (224/751), suspicious for high-grade urothelial carcinoma (SHGUC) was 16.8% (126/751), high grade urothelial carcinoma (HGUC) was 21.2% (159/751), and non-urothelial malignancy (NUM) was 2.1% (16/751). The histpathologic ROHM corresponding to each cytological diagnosis category were 27.3% for NHGUC, 32.7% for AUC, 74.7% for SHGUC, 96.6% for HGUC and 100.0% for NUM, respectively. ROHM of SHGUC was significantly higher than that of AUC group, and the difference between the two groups was statistically significant (P＜0.001). ROHM of HGUC group was significantly higher than that of SHGUC group, and the difference was statistically significant (P＜0.001). With SHGUC as the cut-off value, the sensitivity and specificity of cytological diagnosis of HGUC were 76.7% (165/215) and 85.7% (18/21), and with HGUC as the cut-off value, the sensitivity and specificity of cytological diagnosis of HGUC were 53.0% (114/215) and 100.0% (21/21), respectively. Conclusions Urine cytology has high sensitivity and specificity in the diagnosis of HGUC. The malignant risk of TPS varies with different diagnosis category. The high malignant risk population in cancer hospital leads to the relatively high malignant proportion and ROHM in each diagnosis category. Urinary cytology TPS reporting system is helpful to clinical management and has good clinical application value. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to assess the effectiveness of early single intravesical administration of epirubicin in preventing intravesical recurrence after radical nephroureterectomy for upper tract urothelial carcinoma. Materials and Methods: Patients with upper tract urothelial carcinoma who underwent radical nephroureterectomy between November 2018 and May 2022 were retrospectively reviewed. Intravesical epirubicin was administered within 48 hours if no evidence of leakage was observed. Epirubicin (50 mg) in 50 mL normal saline solution was introduced into the bladder via a catheter and maintained for 60 minutes. The severity of adverse events was graded using the Clavien-Dindo classification. We compared intravesical recurrence rate between the two groups. Multivariate analyses were performed to identify the independent predictors of bladder recurrence following radical nephroureterectomy. Results: Epirubicin (n=55) and control (n=116) groups were included in the analysis. No grade 1 or higher bladder symptoms have been reported. A statistically significant difference in the intravesical recurrence rate was observed between the two groups (11.8% at 1 year in the epirubicin group vs. 28.4% at 1 year in the control group; log-rank p=0.039). In multivariate analysis, epirubicin instillation (hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.20 to 0.93; p=0.033) and adjuvant chemotherapy (HR, 0.29; 95% CI, 0.13 to 0.65; p=0.003) were independently predictive of a reduced incidence of bladder recurrence. Conclusion This retrospective review revealed that a single immediate intravesical instillation of epirubicin is safe and can reduce the incidence of intravesical recurrence after radical nephroureterectomy. However, further prospective trials are required to confirm these findings. [ABSTRACT FROM AUTHOR]