Urinary Bladder Cancer Research Articles

Relationship between Bladder Cancer, Nutritional Supply, and Treatment Strategies: A Comprehensive Review.

Bladder cancer (BC) is the predominant neoplasm affecting the urinary system and ranks among the most widespread malignancies globally. The causes of bladder cancer include genetic factors; age; sex; and lifestyle factors, such as imbalanced nutrition, obesity, and metabolic disorders. The lack of proper nutrient intake leads to the development of bladder cancer because insufficient nutrients are consumed to prevent this disease. The purpose of this review was to analyze the nutrients closely linked to the onset and advancement of bladder cancer and to explore the relationship between dietary nutrients and bladder cancer. Particular emphasis was placed on nutrients that are frequently ingested in daily life, including sugar, fat, protein, and others. The focus of this research was to analyze how nutritional intake before and after surgery affects the recovery process of patients who have been diagnosed with bladder cancer. This article seeks to increase awareness among both society and the medical community about the significance of implementing appropriate dietary nutrition to reduce the chances of developing bladder cancer, enhance perioperative care for patients with bladder cancer, and aid in their recuperation.

Induction therapy with ipilimumab and nivolumab followed by consolidative chemoradiation as organ-sparing treatment in urothelial bladder cancer: study protocol of the INDIBLADE trial.

Studies that assessed the efficacy of pre-operative immune checkpoint blockade (ICB) in locally advanced urothelial cancer of the bladder showed encouraging pathological complete response rates, suggesting that a bladder-sparing approach may be a viable option in a subset of patients. Chemoradiation is an alternative for radical cystectomy with similar oncological outcomes, but is still mainly used in selected patients with organ-confined tumors or patients ineligible to undergo radical cystectomy. We propose to sequentially administer ICB and chemoradiation to patients with (locally advanced) muscle-invasive bladder cancer. The INDIBLADE trial is an investigator-initiated, single-arm, multicenter phase 2 trial. Fifty patients with cT2-4aN0-2M0 urothelial bladder cancer will be treated with ipilimumab 3 mg/kg on day 1, ipilimumab 3 mg/kg plus nivolumab 1 mg/kg on day 22, and nivolumab 3 mg/kg on day 43 followed by chemoradiation. The primary endpoint is the bladder-intact event-free survival (BI-EFS). Events include: local or distant recurrence, salvage cystectomy, death and switch to platinum-based chemotherapy. We will also evaluate the potential of multiparametric magnetic resonance imaging of the bladder to identify non-responders, and we will assess the clearance of circulating tumor DNA as a biomarker for ICB treatment response. This is the first trial in which the efficacy of induction combination ICB followed by chemoradiation is being evaluated to provide bladder-preservation in patients with (locally advanced) urothelial bladder cancer. The INDIBLADE trial was registered on clinicaltrials.gov on January 21, 2022 (NCT05200988).

Diagnostic value of the combination of DAPK methylation in urinary sediment and B ultrasound for recurrent urinary bladder cancer

BackgroundUrinary bladder cancer (UBC) is the most common malignancy affecting the urinary system. This study aimed to investigate the diagnostic value of combining DAPK methylation in urinary sediment and B ultrasound in the detection of recurrent UBC.MethodsA total of 1021 cases with primary UBC who underwent electrocision of bladder tumor through urethra were included in this study and followed up. Various parameters including B ultrasound, DAPK methylation in urinary sediment, examination of exfoliated cells in the urine, and cystoscopy were performed. The data collected was analyzed using the Kappa test, and receiver operating characteristic (ROC) curve was constructed to assess the diagnostic role in recurrent UBC.ResultsAmong the 1021 patients, 115 patients experienced recurrence confirmed by cystoscopy and biopsy within two years and were excluded from the study, resulting in an effective sample size of 906 primary UBC cases. The results of cystoscopy showed agreement with B ultrasound (Kappa = 0.785, P < 0.05), as well as with DAPK methylation in urinary sediment, and the combination of B ultrasound and DAPK methylation (Kappa = 0.517, P < 0.05, Kappa = 0.593, P < 0.05). The combination of B ultrasound with DAPK methylation yielded an area under the curve of 0.922, with a sensitivity of 92.86%, specificity of 91.63%, and a negative predictive value of 99.4%, suggesting that a negative result indicates a low risk of recurrence.ConclusionThe combination of DAPK methylation in urinary sediment with B ultrasound demonstrates high diagnostic performance for recurrent UBC.

Exercise therapy in prehabilitation : Current findings in urology

Prehabilitation refers to interventions that take place before starting medical treatment. Prehabilitation exercise therapy aims to increase functional physical capacities to improve recovery and reduce side effects. To present the evidence and potential of prehabilitation exercise therapy in urological oncology. Compilation and explanation of study results. Studies are limited and primarily focused on prostate and bladder cancer. Current data show positive effects on physical functioning and cardiorespiratory capacity. The majority of prehabilitation studies in prostate cancer focus on specific goals of physical functioning, particularly maintenance and recovery of urinary continence with inconsistent results. There is preliminary evidence to improve cardiorespiratory fitness and overall physical functioning in urinary bladder and prostate cancer. Further in-depth research is needed to map the potential spectrum of prehabilitation exercise therapy in uro-oncology.

Selective targeting of lectins and their macropinocytosis in urothelial tumours: translation from in vitro to ex vivo

Urinary bladder cancer can be treated by intravesical application of therapeutic agents, but the specific targeting of cancer urothelial cells and the endocytotic pathways of the agents are not known. During carcinogenesis, the superficial urothelial cells exhibit changes in sugar residues on the apical plasma membranes. This can be exploited for selective targeting from the luminal side of the bladder. Here we show that the plant lectins Jacalin (from Artocarpus integrifolia), ACA (from Amaranthus caudatus) and DSA (from Datura stramonium) selectively bind to the apical plasma membrane of low- (RT4) and high-grade (T24) cancer urothelial cells in vitro and urothelial tumours ex vivo. The amount of lectin binding was significantly different between RT4 and T24 cells. Endocytosis of lectins was observed only in cancer urothelial cells and not in normal urothelial cells. Transmission electron microscopy analysis showed macropinosomes, endosome-like vesicles and multivesicular bodies filled with lectins in RT4 and T24 cells and also in cells of urothelial tumours ex vivo. Endocytosis of Jacalin and ACA in cancer cells was decreased in vitro after addition of inhibitor of macropinocytosis 5-(N-ethyl-N-isopropyl) amiloride (EIPA) and increased after stimulation of macropinocytosis with epidermal growth factor (EGF). Clathrin, caveolin and flotillin did not colocalise with lectins. These results confirm that the predominant mechanism of lectin endocytosis in cancer urothelial cells is macropinocytosis. Therefore, we propose that lectins in combination with conjugated therapeutic agents are promising tools for improved intravesical therapy by targeting cancer cells.

Vaccination against Extracellular Vimentin for Treatment of Urothelial Cancer of the Bladder in Client-Owned Dogs.

It was recently shown that targeting extracellular vimentin (eVim) is safe and effective in preclinical models. Here, we report the safety and efficacy in client-owned dogs with spontaneous bladder cancer of CVx1, an iBoost technology-based vaccine targeting eVim in combination with COX-2 inhibition. This was a single-arm prospective phase 1/2 study with CVx1 in 20 client-owned dogs with spontaneous UC which involved four subcutaneous vaccinations with CVx1 at 2-week intervals for induction of antibody titers, followed by maintenance vaccinations at 2-month intervals. Additionally, daily cyclooxygenase (COX)-2 inhibition with meloxicam was given. The response was assessed by antibody titers, physical condition, abdominal ultrasound and thorax X-ray. The primary endpoints were the development of antibody titers, as well as overall survival compared to a historical control group receiving carboplatin and COX-2 inhibition with piroxicam. Kaplan-Meier survival analysis was performed. All dogs developed antibodies against eVim. Titers were adequately maintained for the duration of this study. A median overall survival of 374 days was observed, which was 196 days for the historical control group (p < 0.01). Short-term grade 1-2 toxicity at the injection site and some related systemic symptoms peri-vaccination were observed. No toxicity was observed related to the induced antibody response. A limitation of this study is the single-arm prospective setting. CVx1 plus meloxicam consistently induced efficient antibody titers, was well tolerated and showed prolonged survival. The results obtained merit further development for human clinical care.

Effective and Selective Ru(II)-Arene Complexes Containing 4,4'-Substituted 2,2' Bipyridine Ligands Targeting Human Urinary Bladder Cancer Cells.

Cisplatin-based chemotherapy is a common regimen for bladder cancer, a life-threatening cancer with more than 500,000 new cases worldwide annually. Like many other metallodrugs, cisplatin causes severe side effects for its general toxicity. Organoruthenium is known for its structural stability, good anticancer activity, and possible low general toxicity. Here, we have prepared and characterized a series of water-soluble ruthenium-arene complexes with N,N'-chelating ligands: [Ru(II)-η6-arene-(4,4'-(X)2-2,2'-bipyridine)Cl]Cl (arene = p-cymene, X = C4H9 (1), COOH (2), COOCH3 (3), COOC2H5 (4); arene = benzene, X = C4H9 (5), COOCH3 (6), COOC2H5 (7)). These complexes are carefully characterized using single-crystal X-ray diffraction, UV-vis, IR, 1H NMR, and MALDI-TOF MS spectroscopy. Their DFT-calculated structural and thermodynamic properties are consistent with the experimental observations. Biophysicochemical studies of complex interaction with CTDNA and BSA supported by molecular docking simulations reveal suitable properties of 1-7 as anticancer agents. Cytotoxicities of 1-7 are evaluated on healthy human MCF-10a-breast epithelial and African green monkey Vero cells, and carcinoma human HepG-2-hepatic, T24-bladder, and EAhy-926-endothelial cells. All complexes exhibit much higher cytotoxicity for T24 than cisplatin. Particularly, 1 and 2 are also highly selective toward T24. Fluorescence imaging and flow cytometry demonstrate that 1 and 2 penetrate T24 cell membrane and induce early apoptosis at their respective IC50 concentrations, which ultimately lead to cell death. Statistical analysis suggests that the order of importance for T24 cell antiproliferation is protein binding, Log p, Ru-Cl bond length, while DNA binding is the least important. This study is the first to report the anti-bladder cancer efficacy of Ru-arene-2,2'-bipyridine complexes, and may provide insights for rational design of organoruthenium drugs in the enduring search for new chemotherapeutic agents.

Ultrasound versus Nerve Stimulator Guided Obturator Nerve Block in Patients Undergoing Transurethral Resection of Bladder Tumor.

Urinary bladder cancer is more common in geriatric population. Transurethral resection of bladder tumor remains the mainstay of treatment. It is usually performed under subarachnoid block. However, obturator nerve is spared in subarachnoid block that can produce adductor jerk, which is associated with bladder injury, rupture, incomplete resection of tumor and hematoma. To overcome this jerk, selective obturator nerve block is commonly performed. Thus, we conducted this study to compare the efficacy of ultrasound and nerve stimulator-guided techniques for obturator nerve block. This is a prospective, comparative study conducted at a tertiary care hospital in Nepal. Sixty patients, scheduled to undergo Transurethral Resection of Bladder Tumor for lateral and posterolateral wall bladder cancer under subarachnoid block were enrolled and divided into two group having thirty patients in each groups. Group I received 15 ml of 0.25% Bupivacaine to block obturator nerve by using peripheral nerve stimulator. Group II received the same amount of Bupivacaine to block obturator nerve under ultrasound guidance. We evaluated the success of the block, ease of the procedure and complications. The adductor reflex was present in 23.33% of cases with nerve stimulator guided obturator nerve block, whereas, it was16.66% in ultrasound guided technique (p=0.75). The success rate of obturator nerve block was 76.66% in nerve stimulator guided technique, whereas 83.33% in ultrasound guided technique (p= 0.21). 83.33% of obturator nerve block was found to be easy in nerve stimulator guided technique, whereas 66.66 % in ultrasound guided technique (p = 0.14). There were no major complications noted. The findings of this study conclude that both ultrasound and nerve stimulator guided techniques equally abolished the adductor reflexes. Both techniques are easy to perform and safe.

A Validation Study of cT-Categories in the Swedish National Urinary Bladder Cancer Register-Norrland University Hospital.

In Sweden, all patients with urinary bladder cancer (UBC) are recorded in the Swedish National Register for Urinary Bladder Cancer (SNRUBC). The purpose of this study was to validate the registered clinical tumour categories (cT-categories) in the SNRUBC for Norrland University Hospital, Sweden, from 2009 to 2020, inclusive. The medical records of all 295 patients who underwent radical cystectomy for the treatment of UBC were reviewed retrospectively. Possible factors impacting the cT-categories were identified. To optimise cT-classification, computed tomography urography of all patients with suspected tumour-associated hydronephrosis (TAH) or suspected tumour in bladder diverticulum (TIBD) were retrospectively reviewed by a radiologist. Discrepancy was tested with a logistic regression model. cT-categories differed in 87 cases (29.5%). Adjusted logistic regression analysis found TIBD and TAH as significant predictors for incorrect registration; OR = 7.71 (p < 0.001), and OR = 17.7, (p < 0.001), respectively. In total, 48 patients (68.6%) with TAH and 12 patients (52.2%) with TIBD showed discrepancy regarding the cT-category. Incorrect registration was mostly observed during the years 2009-2012. The study revealed substantial incorrect registration of cT-categories in SNRUBC. A major part of the misclassifications was related to TAH and TIBD. Registration of these variables in the SNRUBC might be considered to improve correct cT-classification.

Exposure to benzene and other hydrocarbons and risk of bladder cancer among male offshore petroleum workers

BackgroundOccupational exposures constitute the second leading cause of urinary bladder cancer after tobacco smoking. Increased risks have been found in the petroleum industry, but high-quality exposure data are needed to explain these observations.MethodsUsing a prospective case-cohort design, we analysed 189 bladder cancer cases (1999–2017) and 2065 randomly drawn non-cases from the Norwegian Offshore Petroleum Workers cohort. Cases were identified in the Cancer Registry of Norway, while work histories (1965–1998) and lifestyle factors were recorded by questionnaire at baseline (1998). Occupational petroleum-related hydrocarbon exposures were assessed by expert-developed job-exposure matrices. Hazard ratios were estimated by weighted Cox-regressions, adjusted for age, tobacco smoking, education, and year of first employment, and with lagged exposures.ResultsIncreased risks were found in benzene-exposed workers, either long-term exposure (≥18.8 years, HR = 1.89, 95% CI: 1.14–3.13; p-trend = 0.044) or high-level cumulative benzene exposure (HR = 1.60, 95% CI: 0.97–2.63; p-trend = 0.065), compared with the unexposed. Associations persisted with 20-year exposure lag. No associations were found with skin or inhalation exposure to crude oil, mineral oil (lubrication, hydraulics, turbines, drilling), or diesel exhaust.ConclusionsThe results suggest that exposures in the benzene fraction of the petroleum stream may be associated with increased bladder cancer risk.

Fluorodeoxyglucose positron emission tomography (18F-FDG PET)-computed tomography (CT) in the initial staging of bladder cancer: a single institution experience

BackgroundThe purpose of this study was to assess the usefulness of fluorodeoxyglucose positron emission tomography (18F-FDG PET)-computed tomography (CT) scan for staging urinary bladder cancer. The study also sought to determine the effect of 18F-FDG PET/CT on management decisions and its implications for patient care.MethodsA total of 133 patients with bladder cancer who had both conventional imaging and 18F-FDG PET/CT for initial staging were identified. All 18F-FDG-PET/CT findings were classified as true positive, true negative, false positive, or false negative based on their potential to impact the intent of treatment. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated using the standard definition. Furthermore, the rate of change in therapy intent was determined for the entire sample and for subgroups with non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) patients.ResultsThe overall concordance rate between PET/CT and conventional imaging was around 54%. On conventional images, 18% of patients had localized disease, which was upstaged in 6.8% of cases using 18F-FDG PET/CT. Pelvic lymph node involvement was detected in 18.8% of cases using conventional imaging, which was downstaged to localized disease in 4.5% of cases using 18F-FDG PET/CT. While 63.2% of patients had systemic disease on a CT scan, 24.7% of cases were downstaged using PET/CT. Overall, the rate of change in therapy intent was 26.3% for the entire sample, 24.5% for NMIBC subgroup, and 27.3% for MIBC patients.ConclusionsThe study found that 18F-FDG PET/CT is an effective and accurate tool for staging bladder cancer in newly diagnosed patients. Approximately one quarter of patients had a change in management intent based on 18F-FDG PET/CT results. The study suggests that PET/CT should be used as a standard for newly diagnosed patients, but more research is needed to confirm this.

Study of her2/neu and ki-67 expression in invasive urothelial carcinoma of bladder and their correlation with grade and stage

Urinary bladder cancer is one of the costliest diseases, which requires lifelong surveillance due to its rapid aggressive clinical course. Here, HER2/neu and Ki-67 expression, is studied, as important prognostic marker with therapeutic implications in invasive urothelial bladder carcinoma (IUBC). To study expression of HER2/neu and Ki-67 in histologically diagnosed cases of IUBC and their clinicopathological correlation.An observational, cross-sectional, study was performed in Pathology Department, NRS Medical College, Kolkata, from February 2020 to July 2021. Tissue sections, after proper processing, were stained in H&amp;E. A total of 75 IUBC cases were histopathologically diagnosed with grade and stage. HER2/neu and Ki-67 expression by immunohistochemistry was studied in them; which was compared with clinicopathological variables like age, sex, risk factors, histological type, grade, stage, etc. Statistical analysis software EPI INFO (TM) 7.2.2.2 was used, p&amp;#60;0.05 was taken to be statistically significant.Among 75 cases of IUBC, 60% were high grade and 72% were of lower (pT1) stage. HER2/neu was positive in 52% cases; significantly associated with males, haematuria, smoking, necrosis, high grade (p&amp;#60;0.00001) and higher stage (pT2/3/4) (p=0.0005). Ki-67 index was high in 56% cases; significantly associated with &amp;#62;50 years age group, haematuria, smoking, necrosis, LVI, high grade (p&amp;#60;0.00001) and higher stage (p&amp;#60;0.0001). Positive HER2/neu expression was also significantly associated with high Ki-67 index (p&amp;#60;0.00001).Positive HER2/neu expression and high Ki-67 index is significantly associated with high grade and stage of tumours. So, these patients may be considered for targeted therapy using Trastuzumab in addition to conventional therapy.

The Effect of Statins on the Incidence and Prognosis of Bladder Cancer: A Systematic Review and Meta-Analysis.

Statins are widely used due to their ability to lower plasma cholesterol and offer protection from the effects of atherosclerosis. However, their role in urology and specifically bladder cancer remains unclear. We aimed to systematically address this issue in the literature and determine any possible effects of statin therapy on bladder cancer. We searched MEDLINE (PubMed) and Cochrane Library databases for records up to 26 March 2023, for studies evaluating the effects of statins on urinary bladder cancer (UBC). We included all randomized controlled trials (RCTs), cohorts, and case-control studies that were conducted on the adult population. PROSPERO registration number: CRD42023407795. Database searches returned 2251 reports, and after thorough investigation and assessment for eligibility, 32 reports were included in the analysis. Of them, 4 were RCTs, 6 were case-control studies, and 22 were cohort studies. Our qualitative analysis demonstrated no association between statin administration and UBC local control, recurrence, survival, or mortality, or between statin administration and bacille Calmette-Guérin (BCG) immunotherapy effectiveness. A meta-analysis of 10 trials revealed a non-significant reduction of 11% in UBC risk among users compared with non-users in RCTs (RR: 0.89, 95% CI 0.68-1.16, p = 0.37) and a non-significant increase of 32% of UBC risk among statin users compared with non-users in the analysis of the cohort studies (RR: 1.32, 95% CI 0.76-2.30, p = 0.33). Our results provide strong evidence to support the neutral effect of statins on UBC local control, recurrence, survival, and mortality, and on BCG immunotherapy. Our meta-analysis revealed a non-significant effect on UBC risk among statin users when compared with non-users, indicating no statin effect on UBC incidence and overall prognosis.

Prevalence of self-reported cancer based on sexual orientation in the United States: a comparative analysis between lesbian, bisexual, gay, and heterosexual individuals.

Our study aimed to compare the prevalence and likelihood of self-reported (SR) cancer diagnosis between lesbian, gay, and bisexual (LGB) groups and the heterosexual population in the United States between 2017 and 2021. This study analyzed data from the National Health Interview Survey (NHIS) 2017-2021, which included 134,372 heterosexual and 4576 LGB individuals aged 18 and above. The prevalence of any SR cancer and some selected cancers were calculated for the LGB and compared with heterosexual adults. Sexual orientation was used to predict SR cancer diagnosis for each sex using multiple logistic regression, adjusting for other sociodemographic determinants. The unadjusted prevalence of any SR cancer among the LGB population was 9.0%. Lesbian and Bisexual women had higher prevalence of SR cancer of the cervix, uterus, ovary, thyroid, bone, skin melanoma, leukemia, and other blood cancers than Heterosexual women. Gay and Bisexual men had a higher prevalence of SR cancer of the bladder, kidney, skin (non-melanoma, and other kinds), bone, lymphoma, and leukemia than Heterosexual men. After adjusting for other socio-demographic factors, gay men were 1.73 (CI 1.14-2.63, p = 0.01) times more likely than heterosexual men to be diagnosed with cancer, while lesbian women were 2.26 (CI 1.24-4.16, p = 0.009) times more likely to be diagnosed with cancer than heterosexual women. Some sexual minority subgroups are more likely to be diagnosed with cancer than their heterosexual counterparts. As a result, more research and SM-specific intervention efforts should focus on cancer risk assessment, screening, prevention, treatment, and survivorship in SM populations.

Prognosis of Patients Receiving Chemotherapy for Metastatic Upper Tract Urothelial Carcinoma Compared With Metastatic Urinary Bladder Cancer.

The treatment strategy for metastatic upper tract urothelial carcinoma (mUTUC) is currently based on the evidence from metastatic urinary bladder cancer (mUBC). However, some reports have shown that the outcomes of UTUC differ from those of UBC. Therefore, we retrospectively analyzed the prognosis of patients with mUBC and mUTUC treated with first-line platinum-based chemotherapy. Patients who underwent platinum-based chemotherapy at the Kindai University Hospital and affiliated hospitals between January 2010 and December 2021 were included in the study. There were 56 patients with mUBC and 73 with mUTUC. Kaplan-Meier curves were used to estimate progression-free (PFS) and overall (OS) survival. Multivariate analyses were performed using Cox proportional hazards model to predict prognostic factors. The median PFS was 4.5 and 4.0 months for the mUBC and mUTUC groups, respectively (p=0.094). The median OS was 17.0 months for both groups (p=0.821). The multivariate analysis showed no prognostic factor for PFS. The multivariate analysis for OS showed that younger age at the initiation of chemotherapy and immune checkpoint inhibitor use after first-line therapy were significantly associated with better OS. Platinum-based chemotherapy had a similar effect on patients with mUTUC and mUBC.

Outcome of Treating Urinary Bladder Cancer in Sohag University Hospital

Outcome of Treating Urinary Bladder Cancer in Sohag University Hospital

Socio-economic, education, and insurance-related factors associated with the treatment completion rates in patients with nonmetastatic urinary bladder cancer: A Retrospective cohort study.

Among urological malignancies, the diagnosis and treatment of urinary bladder cancer (UBC) incurs the highest cost per patient. Our objective was to broaden the current understanding of how demographic, socioeconomic, education, and insurance-related factors influence UBC management. Between January 2017 and December 2019, all patients with nonmetastatic bladder cancer were included. The demographic, treatment, and follow-up details were retrieved from a prospectively maintained database, and the Modified Kuppuswamy Index was used to evaluate the patients' socioeconomic level. Patients were divided into the completed treatment group, or the incomplete treatment group based on adherence to the initially intended treatment plan. Patients who presented with benign disease or metastases were not included. Eighty-nine patients did not complete the initially intended course of treatment out of 132 patients who needed additional management after the initial transurethral resection. Comparable risk factors and demographic profiles existed in both groups. Patients with intermediate-risk disease are more likely to fail to adhere to the initial intended treatment (odds ratio [OR] = 0.09; 95% confidence interval [CI]: 0.02-0.30). On logistic regression analysis, upper socioeconomic status (OR = 6.8; 95% CI: 0.35-132.1) patients and patients with higher educational status of graduation or above (OR = 3.62; 95% CI: 0.75-17.43) had higher chances of treatment completion. Education status significantly impacted treatment completion on multivariate analysis (P = 0.01). Patients who utilized employer-funded insurance had better treatment compliance (OR = 4.1; 95% CI: 0.90-18.7). The compliance was unaffected by smoking, occupation, or other demographic factors. Patients with low economic status, low levels of education, and who need adjuvant intravesical therapy had considerably greater treatment dropout rates.

International Society of Urological Pathology (ISUP) Consensus Conference on Current Issues in Bladder Cancer. Working Group 2: Grading of Mixed Grade, Invasive Urothelial Carcinoma Including Histologic Subtypes and Divergent Differentiations, and Non-Urothelial Carcinomas.

The 2022 International Society of Urological Pathology (ISUP) Consensus Conference on Urinary Bladder Cancer Working Group 2 was tasked to provide evidence-based proposals on the applications of grading in noninvasive urothelial carcinoma with mixed grades, invasive urothelial carcinoma including subtypes (variants) and divergent differentiations, and in pure non-urothelial carcinomas. Studies suggested that predominantly low-grade noninvasive papillary urothelial carcinoma with focal high-grade component has intermediate outcome between low- and high-grade tumors. However, no consensus was reached on how to define a focal high-grade component. By 2004 WHO grading, the vast majority of lamina propria-invasive (T1) urothelial carcinomas are high-grade, and the rare invasive low-grade tumors show only limited superficial invasion. While by 1973 WHO grading, the vast majority of T1 urothelial carcinomas are G2 and G3 and show significant differences in outcome based on tumor grade. No consensus was reached if T1 tumors should be graded either by the 2004 WHO system or by the 1973 WHO system. Because of the concern for underdiagnosis and underreporting with potential undertreatment, participants unanimously recommended that the presence of urothelial carcinoma subtypes and divergent differentiations should be reported. There was consensus that the extent of these subtypes and divergent differentiations should also be documented in biopsy, transurethral resection, and cystectomy specimens. Any distinct subtype and divergent differentiation should be diagnosed without a threshold cutoff, and each type should be enumerated in tumors with combined morphologies. The participants agreed that all subtypes and divergent differentiations should be considered high-grade according to the 2004 WHO grading system. However, participants strongly acknowledged that subtypes and divergent differentiations should not be considered as a homogenous group in terms of behavior. Thus, future studies should focus on individual subtypes and divergent differentiations rather than lumping these different entities into a single clinicopathological group. Likewise, clinical recommendations should pay attention to the potential heterogeneity of subtypes and divergent differentiations in terms of behavior and response to therapy. There was consensus that invasive pure squamous cell carcinoma and pure adenocarcinoma of the bladder should be graded according to the degree of differentiation. In conclusion, this summary of the International Society of Urological Pathology Working Group 2 proceedings addresses some of the issues on grading beyond its traditional application, including for papillary urothelial carcinomas with mixed grades and with invasive components. Reporting of subtypes and divergent differentiation is also addressed in detail, acknowledging their role in risk stratification. This report could serve as a guide for best practices and may advise future research and proposals on the prognostication of these tumors.

Exploring the anticancer potential of thiadiazole derivatives of substituted thiosemicarbazones formed via copper‐mediated cyclization

A couple of N‐(4)‐morpholine/pyrrolidine‐substituted thiosemicarbazones (TSCs) of fluorene‐2‐carboxaldehyde (FM and FP), and their corresponding thiadiazoles (TDZs) (CFM and CFP), were synthesized and characterized (elemental analysis, ultraviolet–visible [UV–Visible], Fourier transform infrared [FT‐IR], nuclear magnetic resonance [NMR; 1H &amp; 13C], high‐resolution mass spectrometry [HRMS], and single‐crystal X‐ray diffraction [SCXRD]) for the evaluation of their anticancer potential. The TDZs were obtained unexpectedly and are possibly formed via single‐step metal (copper)‐mediated oxidative cyclizations of the TSCs. The synthesized compounds are fairly stable in phosphate buffer at the biological pH of 7.4. The density functional theory [DFT] studies were performed to predict the optimized structures and physicochemical properties of these compounds. The compounds were further subjected to computational and experimental biomolecular investigations in order to evaluate their anticancer activity in detail. CFM had the most potent activity against human breast adenocarcinoma (MCF‐7) and human urinary bladder (T24) cancer cells, with IC50 values of 12.00 and 24.80 μM, respectively. In contrast, CFM had negligible cytotoxicity (IC50 = 98.70 μM) against kidney epithelial cells extracted from an African green monkey (Vero) normal cells. This outcome was preferable to that of the widely used medicine Cisplatin. Molecular docking studies were performed with the breast cancer protein “cytochrome P450 1A1” (CYP1A1) and bovine serum albumin (BSA) to predict how effectively the compounds bind to the receptor. The ADMET findings suggest that these compounds have considerable drug‐likeness and oral bioavailability. These insights may open the door for additional medical research into the bioactivities of TSCs and TDZs produced from bioactive carbonyl compounds.

The genetic associations of COVID-19 on genitourinary symptoms.

Recently emerged reports indicated that patients with coronavirus disease 2019 (COVID-19) might experience novo genitourinary symptoms after discharge. Nevertheless, the causal associations and underlying mechanisms remain largely unclear. Genome-wide association study (GWAS) statistics for COVID-19 and 28 genitourinary symptoms with consistent definitions were collected from the COVID-19 Host Genetic Initiative, FinnGen, and UK Biobanks. Mendelian randomization (MR) analyses were applied to explore the causal effects of COVID-19 on genitourinary symptoms by selecting single-nucleotide polymorphisms as instrumental variables. Meta-analyses were conducted to evaluate the combined causal effect. Molecular pathways connecting COVID-19 and its associated disorders were evaluated by weighted gene co-expression network analysis (WGCNA) and enrichment analyses to extract insights into the potential mechanisms underlying the connection. The MR and meta-analyses indicated that COVID-19 was causally associated with increased risk for calculus of the lower urinary tract (LUTC, OR: 1.2984 per doubling in odds of COVID-19, 95% CI: 1.0752-1.5680, p = 0.007) and sexual dysfunction (SD, OR: 1.0931, 95% CI: 1.0292-1.1610, p = 0.004). Intriguingly, COVID-19 might exert a slight causal protective effect on the progression of urinary tract infections (UTIs) and bladder cancer (BLCA). These results were robust to sensitivity analyses. Bioinformatic analyses indicated that the inflammatory-immune response module may mediate the links between COVID-19 and its associated disorders at the molecular level. In response to post-COVID-19 symptoms, we recommend that COVID-19 patients should strengthen the prevention of LUTC and the monitoring of sexual function. Meanwhile, the positive effects of COVID-19 on UTIs and BLCA should attach equal importance.