High peripheral neutrophil and monocyte count distinguishes renal cell carcinoma from renal angiomyolipoma and predicts poor prognosis of renal cell carcinoma.

Background: The presence of peripheral inflammatory cells has been linked to the prognosis of cancer. This study aims to investigate the distinct roles of absolute neutrophil count (ANC) and absolute monocyte count (AMC) in differentiating renal cell carcinoma (RCC) from renal angiomyolipoma (RAML), as well as their prognostic significance in RCC. Methods: We conducted a comprehensive analysis of peripheral immune cell data, clinicopathological data, and tumor characteristics in patients diagnosed with RCC or RAML from January 2015 to December 2021. Receiver operating characteristic (ROC) curves, as well as univariate and multivariate analyses, were employed to assess the diagnostic utility of AMC and ANC in differentiating between RCC and RAML. Kaplan-Meier curve analysis was used to study the survival of RCC patients with different AMC and ANC. The prognostic value of AMC and ANC in RCC was investigated using COX univariate and multivariate analysis. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used for bioinformatic correlation analysis. Results: A total of 1120 eligible patients were included in the study. The mean preoperative AMC and ANC in patients with RCC were found to be significantly higher compared to those in patients with RAML (P = 0.001 and P < 0.001, respectively). High preoperative AMC and ANC significantly correlated with smoking history, tumor length, gross hematuria, and high T Stage, N stage, and pathological grade. In multivariate analyses, an ANC> 3.205 *10^9/L was identified to be independently associated with the presence of RCC (HR = 1.618, P = 0.008). High AMC and ANC were significantly associated with reduced OS and PFS (P < 0.05), and ANC may be an independent prognostic factor. Public database analysis showed that signature genes of tumor-associated macrophages (TAMs) and tumor-associated neutrophils (TANs) were highly expressed in ccRCC. Conclusions: Elevated preoperative ANC and AMC can distinguish RCC from RAML and predict poor prognosis in patients with RCC. Furthermore, the signature genes of TAMs and TANs exhibit high expression levels in clear cell RCC.

Laparoscopic pyelotomy combined with ultrasonic lithotripsy via a nephroscope for the treatment of complex renal stones.

The purpose of the study was to introduce a novel surgical approach of combining laparoscopic pyelotomy with ultrasonic lithotripsy via a nephroscope for the treatment of complex renal stones. Between May 2021 and April 2023, 32 patients underwent laparoscopic pyelotomy combined with ultrasonic lithotripsy via a nephroscope and their perioperative variables were retrospectively collected and outcomes were assessed. Dissection and incision of the anterior renal pelvis wall was performed via a laparoscope. A 19.5 F nephroscope was introduced into the renal pelvis through a laparoscopic trocar from the incision. Stones were fragmented and sucked out using a 3.3 mm ultrasonic probe placed through the nephroscope. All operations were completed successfully and the stone-free rate at 3 days after operation was 87.5% (28/32). Four (12.5%, 4/32) patients with staghorn stones had a small residual stone in the lower calyx after operation and did not require reintervention. No patient required perioperative transfusion and four (12.5%, 4/32) patients with struvite stones developed postoperative fever, which was successfully treated with intravenous antibiotics. The mean follow-up time was 14.0 ± 7.2 months, with no patient developing long-term complications. This approach offers a safe and effective treatment option for complex renal stones, as the method exhibits a high clearance rate with few complications.

PBRM1 mutation and WDR72 expression as potential combinatorial biomarker for predicting the response to Nivolumab in patients with ccRCC: a tumor marker prognostic study.

PURPOSE: Immune checkpoint therapy (ICT) provides a new idea for the treatment of advanced clear cell renal cell carcinoma (ccRCC), which can bring significant benefits to patients. However, the clinical application of ICT is limited because of the lack of predictive biomarkers to select potential responders. This study aims to propose a new biomarker to predict the response to Nivolumab in patients with ccRCC. MATERIALS AND METHODS: The genes that significantly improve the prognosis of ccRCC were retrieved from The Cancer Genome Atlas (TCGA) database. The genomic and clinical data were from patients that had been registered in prospective clinical trials (CheckMate 009, CheckMate 010 and CheckMate 025). TCGA, Gene Expression Omnibus (GEO), and The Human Protein Atlas database were used to analyze the gene and protein expression of WD repeat-containing protein 72 (WDR72) in ccRCC. Gene Ontology (GO) & The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) were performed to dig relevant mechanisms of WDR72. Single sample gene set enrichment analysis (ssGSEA) was conducted to evaluate the role of WDR72 in immune infiltration. Cell proliferation assay, FAO and ATP quantification were used to explore and verify the molecular mechanisms. The expression of WDR72, FOXP3, CD8, and CPT1A was examined by IHC in 20 advanced ccRCC tissue samples at the Urology Department of our hospital. The MethSurv was used to identify PBRM1 and WDR72 gene methylation and its effect on prognosis of ccRCC. RESULTS: WDR72 is the most significant gene for improving overall survival (OS) in ccRCC. In all three checkmates, OS and progression free survival (PFS) were found to be significantly higher in WDR72 high expression group than that in WDR72 low expression group (P=0.040 and P=0.012, respectively), and similar conclusions could be drawn from the PBRM1-mutation (MUT) compared with the PBRM1-wildtype (WT) (P=0.007 and P=0.006, respectively). What's more, high expression of WDR72 plus PBRM1-MUT as a combinatorial biomarker showed improved OS (HR=0.388, P=0.0026) and PFS (HR=0.39, P=0.0066) compared to low expression of WDR72 plus PBRM1-WT. Functional enrichment analysis showed that WDR72 was closely positively related to fatty acid degradation and fatty acid beta oxidation pathway in ccRCC. In vitro experiments showed that high expression of WDR72 can promote fatty acids oxidation and inhibit the proliferation of ccRCC cells. Immune analysis revealed that WDR72 high expression was associated with decreased infiltration of Treg cells and low ssGSEA score of check-point. IHC results showed that WDR72 was negatively correlated with FOXP3 expression (r=-0.506, P=0.023) and positively correlated with CPT1A expression (r=0.529, P=0.017). CONCLUSIONS: The present study indicated that high expression of WDR72 may indicate a good prognosis of patients treated with Nivolumab and WDR72 expression combined with PBRM1 mutation could be more persuasive to predict the response for ICT in ccRCC patients.

The vascular and morphological characteristics of tumors under narrow-band imaging as predictors for the grade and stage of bladder cancer: a prospective and multi-center study.

The vascular and morphological features of tumors are important predictors of the nature, grade, and stage of various cancers. However, this association has not been tested in bladder cancer. The aim of our study was to investigate the correlation between the morphological characteristics of tumor vessels and the nature, stage and grade of bladder cancer. Between November 2021 and March 2023, we prospectively collated clinical information and cystoscopy information from a series of patients with bladder cancer. Univariate and multivariate logistic regression analysis were used to identify independent risk factors for the nature, grade and stage of bladder cancer. Our analysis showed that cauliflower-like tumors, dotted vessels, and circumferential vessels were independent risk factors for bladder cancer. Reticular vessels were an independent risk factor for high-grade bladder cancer. Thick branching vessels in bladder tumors, along with a wide base, were independent risk factors for the invasion of bladder cancer into the lamina propria. Primary diagnosis, lesion location (beside the left ureteral orifice) and obscure lesion boundaries were all identified as independent risk factors for muscle invasive bladder cancer.

Development and validation of a predictive model for the diagnosis of bladder tumors using narrow band imaging.

PURPOSE: At present, the prediction of bladder tumor nature during cystoscopy is partially dependent on the clinician's own experience. Subjective factors may lead to excessive biopsy or delayed treatment. The purpose of our study is to establish a reliable model for predicting the nature of bladder tumors using narrow band imaging. METHODS: From November 2021 to November 2022, the clinical data of 231 patients who required a cystoscopy were prospectively collected at our center. Cystoscopy was performed in 219 eligible patients, in which both tumor and vascular morphology characteristics were recorded. Pathological results were used as the diagnostic standard. A logistic regression analysis was used to screen out factors related to tumor pathology. Bootstrap resampling was used for internal validation. A total of 71 patients from four other centers served as an external validation cohort. RESULTS: The following diagnostic factors were identified: tumor morphology (cauliflower-like or algae-like lesions), vascular morphology (dotted or circumferential vessels), tumor boundary (clear or unclear), and patients' symptoms (gross hematuria) and were included in the prediction model. The internal validation results showed that the area under the curve was 0.94 (95% CI 0.92-0.97), and the P value from the goodness-of-fit test was 0.97. After external validation, the results showed the area under the curve was 0.89 (95% CI 0.82-0.97) and the P value of the goodness-of-fit test was 0.24. CONCLUSION: A diagnostic prediction nomogram was established for bladder cancer. The verification results showed that the prediction model has good prediction performance.

Sunitinib treatment promotes metastasis of drug-resistant renal cell carcinoma via TFE3 signaling pathway.

Receptor tyrosine kinase (RTK) inhibitors, such as sunitinib and sorafenib, remain the first-line drugs for the treatment of mRCC. Acquired drug resistance and metastasis are the main causes of treatment failure. However, in the case of metastasis Renal Cell Cancer (mRCC), which showed a good response to sunitinib, we found that long-term treatment with sunitinib could promote lysosome biosynthesis and exocytosis, thereby triggering the metastasis of RCC. By constructing sunitinib-resistant cell lines in vivo, we confirmed that TFE3 plays a key role in the acquired resistance to sunitinib in RCC. Under the stimulation of sunitinib, TFE3 continued to enter the nucleus, promoting the expression of endoplasmic reticulum (ER) protein E-Syt1. E-Syt1 and the lysosomal membrane protein Syt7 form a heterodimer, which induces ER fragmentation, Ca2+ release, and lysosomal exocytosis. Lysosomal exocytosis has two functions: pumping sunitinib out from the cytoplasm, which promotes resistance to sunitinib in RCC, releasing cathepsin B (CTSB) into the extracellular matrix (ECM), which can degrade the ECM to enhance the invasion and metastasis ability of RCC. Our study found that although sunitinib is an effective drug for the treatment of mRCC, once RCC has acquired resistance to sunitinib, sunitinib treatment will promote metastasis.

Clinical evaluation of the multifunctional suprapubic catheter in patients requiring permanent suprapubic cystostomy: A prospective randomised trial in a single centre.

AIMS AND OBJECTIVES: To assess the clinical effect of the multifunctional suprapubic catheter (MSC) on occurrence of cystospasm, catheter occlusion, the catheter-related urinary tract infection and remission of overactivity bladder, by comparing with the conventional suprapubic catheter (CSC) in patients with permanent suprapubic cystostomy. BACKGROUND: The conventional suprapubic catheter usually presents with high incidence of catheter-associated complications. DESIGN: A prospective randomised clinical trial in a single centre. METHODS: Between January 2014 and January 2015, a total of 91 consecutive patients with permanent suprapubic cystostomy were prospectively randomised into two groups: the MSC group (n = 43) and CSC group (n = 48). RESULTS: Our results showed that the total times of cystospasm in the MSC group were significantly less than that in the CSC group during the follow-up time (p < .001). In addition, the mean spasmodic duration per time in the MSC group was significantly shorter than that in the CSC group (p < .001). Besides, catheter occlusions were observed in 23 (25.27%) patients, including 5 (11.63%) in the MSC group and 18 (37.50%) in the CSC group (p = .005). The lower rate of positive urine culture was also found in the MSC group but with no significant difference (p = .540). Furthermore, the urodynamic measurement data demonstrated that the patients in the MSC group had a greater remission rate of overactivity bladder after catheter change (p < .001). CONCLUSIONS: The present data showed that the multifunctional suprapubic catheter could significantly reduce the incidence of catheter occlusion, ameliorate the symptom of cystospasm and relieve the overactivity bladder, but have no influence on the catheter-related urinary tract infection. RELEVANCE TO CLINICAL PRACTICE: The application of our self-devised multifunctional suprapubic catheter may result in better management of the patients with permanent suprapubic cystostomy.

Mesenchymal Stem Cells Promote Tumor Progression via Inducing Stroma Remodeling on Rabbit VX2 Bladder Tumor Model.

Background and aim: Mesenchymal stem cells (MSCs) are capable of impacting tumor progression but its role in tumor stroma remodeling still remains unclear. This present study was aimed to evaluate the potential function of MSCs on tumor stroma remodeling using rabbits VX2 bladder tumor model. Methods: The VX2 bladder tumor models were established by injecting mixed cell suspensions (106 of VX2 tumor cells and 0/106/107 of autologous MSCs in group A, B, C, respectively) into the bladder mucosa using thirty male New Zealand white rabbits. The tumor volume was measured by ultrasound at the time points of 1st, 2nd, 3rd and 4th week after inoculation. At the end of the fourth week, the tumor tissue expressions of basic fibroblast growth factor (bFGF), transforming growth factor beta 1 (TGFß-1), hepatocyte growth factor (HGF), matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9) were determined using Real-time quantitative PCR and immunohistochemistry. Masson trichrome staining and Cy3-FITC double-labelled immunofluorescence staining were used to determine the MSCs distribution in tumor tissue in another two rabbits implanted with a cell suspension of 106 VX2 tumor cells and 106 autologous MSCs. Results: MSCs were homogeneously distributed in tumor tissues after 7 days of inoculation, which were not consistent with the distribution of tumor stroma. After 21 days of inoculation, MSCs have been integrated into tumor interstitial tissue and mainly distributed in the mesenchyma around the tumor nest. At the 1st, 2nd, 3rd and 4th week time point, tumor volume in group A < group B < group C, and the difference has statistical significance (all p<0.001).The relative mRNA and protein levels of bFGF, TGFß-1 and HGF were significantly higher in group B and C compared with group A (all p<0.05), as well as the mRNA levels of bFGF, HGF were higher in group C than group B (p<0.05), and the protein levels of bFGF, TGFß-1 were higher in group C than group B (p<0.05). The mRNA and protein levels of MMP2 were significantly higher in group B, C than group A (p<0.05). MMP9 was increasingly over expressed along with the growing amount of MSCs inoculated within tumor, both at the level of mRNA and protein (all p<0.05). Conclusion: MSCs participate in tumor stroma remodeling via inducing overexpression of some important growth factors and MMPs.

Design and synthesis of furyl/thineyl pyrroloquinolones based on natural alkaloid perlolyrine, lead to the discovery of potent and selective PDE5 inhibitors.

Based on perlolyrine (1), a natural alkaloid with weak PDE5 potency from the traditional Chinese aphrodisiac plant Tribulus terrestris L., a series α-substituted tetrahydro-ß-carboline (THßC) derivatives were synthesized via T+BF4--mediated oxidative C-H functionalization of N-aryl THßCs with diverse potassium trifluoroborates. Following Winterfeldt oxidation afforded the corresponding furyl/thienyl pyrroloquinolones, of which 5-ethylthiophene/ethylfuran derivatives 20a-b were identified as the most potent and selective PDE5 inhibitors. Among the enantiomers, (S)-20a and (S)-20b (IC50 = 0.52 and 0.39 nM) were found to be more effective than their (R)-antipode, display favorable pharmacokinetic profiles, exert in vitro vasorelaxant effects on the isolated thoracic aorta, and exhibit in vivo efficacy in the anesthetized rabbit erectile model.

Pro-metastatic activity of AGR2 interrupts angiogenesis target bevacizumab efficiency via direct interaction with VEGFA and activation of NF-κB pathway.

Anterior gradient 2 (AGR2), an endoplasmic reticulum (ER)-resident protein-disulfide isomerase (PDI), is associated with cancer development and malignant progression. Here, we show that high level of AGR2 promotes the aggressive phenotype of prostate cancer (PCa) mouse models developed by either patient-derived xenografts or surgical intra-prostate implantation of PCa cells, associated with enrichment of the blood vessel network in tumor tissues. Angiogenesis markers VEGFR2 and CD34, accompanied with the invasive marker Vimentin, were predominantly stained in metastatic liver tissues. Secreted AGR2 was defined to enhance VEGFR2 activity as evidenced by physical interaction of purified recombinant human AGR2 (rhAGR2) with rhVEGFA through the formation of a disulfide bond. Mutant or deleted thioredoxin motif in rhAGR2 was also unable to bind to rhVEGFA that led to the significant abolishment in the vessel formation, but partially affecting the aggressive process, implicating alternative mechanisms are required for AGR2-conferring metastasis. Cytosolic AGR2 contributed to cell metastasis ascribed to its stabilizing effect on p65 protein, which subsequently activated the NF-κB and facilitated epithelial to mesenchymal transition (EMT). Importantly, GSH and cabozantinib, but not bevacizumab, effectively blocked the pro-angiogenic effect of rhAGR2 in vitro and in vivo, providing evidence that secreted AGR2 acts as a predictive biomarker for selection of angiogenesis-targeting therapeutic drugs based on its levels in the circular system.

Downregulation of reticulocalbin-1 differentially facilitates apoptosis and necroptosis in human prostate cancer cells.

Reticulocalbin 1 (RCN1), an endoplasmic reticulum (ER)-resident Ca2+ -binding protein, is dysregulated in cancers, but its pathophysiological roles are largely unclear. Here, we demonstrate that RCN1 is overexpressed in clinical prostate cancer (PCa) samples, associated with cyclin B, not cyclin D1 expression, compared to that of benign tissues in a Chinese Han population. Downregulation of endogenous RCN1 significantly suppresses PCa cell viability and arrests the cell cycles of DU145 and LNCaP cells at the S and G2/M phases, respectively. RCN1 depletion causes ER stress, which is evidenced by induction of GRP78, activation of PERK and phosphorylation of eIF2α in PCa cells. Remarkably, RCN1 loss triggers DU145 cell apoptosis in a caspase-dependent manner but mainly causes necroptosis in LNCaP cells. An animal-based analysis confirms that RCN1 depletion suppresses cell proliferation and promotes cell death. Further investigations reveal that RCN1 depletion leads to elevation of phosphatase and tensin homolog (PTEN) and inactivation of AKT in DU145 cells. Silencing of PTEN partially restores apoptotic cells upon RCN1 loss. In LNCaP cells, predominant activation of CaMKII is important for necroptosis in response to RCN1 depletion. Thus, RCN1 may promote cell survival and serve as a useful target for cancer therapy.

Changes in mast cell infiltration: a possible mechanism in detrusor overactivity induced by visceral hypersensitivity.

OBJECTIVE: To establish the detrusor overactivity (DO) model induced by visceral hypersensitivity (VH) and investigate the relationship between mast cell (MC) infiltration and DO. MATERIALS AND METHODS: Sixty rats are divided into 4 groups randomly: Group 1:Baseline group; Group 2: DO group; Group 3: CON group; Group 4: VH group. The colorectal distension (CRD) and abdominal withdral reflex (AWR) scores are performed to evaluate VH. The cystometric investigation and histological test of MC infiltration are assessed. RESULTS: The threshold pressure of CRD in the VH group is significantly lower than that in the CON group (P<0.001). At the distension pressure ≥20 mmHg, the AWR scores of the VH group are significantly higher than those of the CON group (10 mmHg: P=0.33; 20 mmHg: P=0.028; 40 mmHg: P<0.001; 60 mmHg: P<0.001; 80 mmHg: P<0.001). DO model is successfully established in the VH group (DO rate=100%). Compared with the CON group, the numbers of MC infiltration are significantly increased in the VH group, including submucosa of bladder (P<0.001), mucosa lamina propria/mesentery of small intestine (P<0.001), and mucosa lamina propria/mesentery of large intestine (P<0.001). Furthermore, more MC activation as well as degranulation are observed in the VH group. CONCLUSIONS: It is indicated that DO model can be established in the VH rats. The MC infiltration may play an important role in DO induced by VH, and may be helpful to understand the mechanisms of DO in VH patients.

Changes in mast cell infiltration: a possible mechanism in detrusor overactivity induced by visceral hypersensitivity

ABSTRACT Objective: To establish the detrusor overactivity (DO) model induced by visceral hypersensitivity (VH) and investigate the relationship between mast cell (MC) infiltration and DO. Materials and Methods: Sixty rats are divided into 4 groups randomly: Group 1:Baseline group; Group 2: DO group; Group 3: CON group; Group 4: VH group. The colorectal distension (CRD) and abdominal withdral reflex (AWR) scores are performed to evaluate VH. The cystometric investigation and histological test of MC infiltration are assessed. Results: The threshold pressure of CRD in the VH group is significantly lower than that in the CON group (P<0.001). At the distension pressure ≥20 mmHg, the AWR scores of the VH group are significantly higher than those of the CON group (10 mmHg: P=0.33; 20 mmHg: P=0.028; 40 mmHg: P<0.001; 60 mmHg: P<0.001; 80 mmHg: P<0.001). DO model is successfully established in the VH group (DO rate=100%). Compared with the CON group, the numbers of MC infiltration are significantly increased in the VH group, including submucosa of bladder (P<0.001), mucosa lamina propria/mesentery of small intestine (P<0.001), and mucosa lamina propria/mesentery of large intestine (P<0.001). Furthermore, more MC activation as well as degranulation are observed in the VH group. Conclusions: It is indicated that DO model can be established in the VH rats. The MC infiltration may play an important role in DO induced by VH, and may be helpful to understand the mechanisms of DO in VH patients.

Improved model for the establishment and evaluation of detrusor overactivity in female Wistar rats.

OBJECTIVE: To improve the model for establishment and evaluation of detrusor overactivity in female Wistar rats. MATERIALS AND METHODS: We ligated the perineal urethra of female Wistar rats and then performed filling cystometry. The probability of detrusor overactivity, bladder capacity, peak voiding pressure and histological changes were investigated. RESULTS: Detrusor overactivity ratio of the obstruction group was 32.4%. Bladder capacity increased from 0.273 ± 0.036 mL in control group to 0.89 ± 0.19 mL in detrusor overactivity group (P < 0.001), and peak voiding pressure increased from 45.9 ± 4.1 cm.H2O to 63.5 ± 17.4 cm.H2O (P = 0.007). For obstruction group, compared to no detrusor overactivity rats, detrusor overactivity rats had higher bladder capacity (0.89 ± 0.19 mL versus 0.43 ± 0.09 mL, P < 0.001) and higher peak voiding pressure (63.5 ± 17.4 cm.H2O versus 44.8 ± 6.2 cm.H2O, P = 0.005). Detrusor overactivity rats were classified according to peak voiding pressure (49.2 ± 4.2 cm.H2O versus 80.8 ± 7.1cm.H2O, P < 0.001). Moreover, bladder weight increased significantly in detrusor overactivity rats (P = 0.003, P = 0.028) and detrusor histological hypertrophy was observed. CONCLUSIONS: Ligating perineal urethra and filling cystometry with intra-urethral cannula approach is a simple and easily reproducible method to establish and evaluate the model of detrusor overactivity in rats.

Improved model for the establishment and evaluation of detrusor overactivity in female Wistar rats

Objective To improve the model for establishment and evaluation of detrusor overactivity in female Wistar rats. Materials and Methods We ligated the perineal urethra of female Wistar rats and then performed filling cystometry. The probability of detrusor overactivity, bladder capacity, peak voiding pressure and histological changes were investigated. Results Detrusor overactivity ratio of the obstruction group was 32.4%. Bladder capacity increased from 0.273 ± 0.036mL in control group to 0.89 ± 0.19mL in detrusor overactivity group (P < 0.001), and peak voiding pressure increased from 45.9 ± 4.1 cm.H2O to 63.5 ± 17.4cm.H2O (P = 0.007). For obstruction group, compared to no detrusor overactivity rats, detrusor overactivity rats had higher bladder capacity (0.89 ± 0.19mL versus 0.43 ± 0.09mL, P < 0.001) and higher peak voiding pressure (63.5 ± 17.4cm.H2O versus 44.8 ± 6.2cm.H2O, P = 0.005). Detrusor overactivity rats were classified according to peak voiding pressure (49.2 ± 4.2cm.H2O versus 80.8 ± 7.1cm.H2O, P < 0.001). Moreover, bladder weight increased significantly in detrusor overactivity rats (P = 0.003, P = 0.028) and detrusor histological hypertrophy was observed. Conclusions Ligating perineal urethra and filling cystometry with intra-urethral cannula approach is a simple and easily reproducible method to establish and evaluate the model of detrusor overactivity in rats. .

Biomarkers in urothelial carcinoma of the bladder: the potential cross-talk between transforming growth factor-ß1 and estrogen receptor ß/androgen receptor pathways.

Urothelial carcinoma of the bladder is nearly three times more common in men than in women. Although it has been primarily attributed to differences in exposure to smoking and industrial chemicals, it is evident now that hormonal factors also play a role. One of the explanations for the differential biologic aggressiveness of urothelial carcinoma of the bladder between genders has focused on sex steroid hormones and their receptors. Recent studies indicated that both estrogen receptor ß and androgen receptor have a role within urothelial carcinoma of the bladder and their expression and activity are altered in the carcinogenesis and progression. Moreover, expression of transforming growth factor-ß1 is a strong predictor of recurrence and specific mortality. We conjecture about the potential cross-talk between transforming growth factor-ß1 and estrogen receptor ß/androgen receptor pathways. Clinical significance of expression of transforming growth factor-ß1 could be improved, when they are related with the determination of estrogen receptor ß/androgen receptor status. Further subgrouping of transforming growth factor-ß1 level combined with estrogen receptor ß/androgen receptor status, would be more accurately determine the prognosis of patients. This hypothesis could be easily verified in corresponding clinical research, and combined analysis of expression of TGF-ß1 and ERß/AR signaling proteins may provide clinicians useful information regarding tumor initiation and progression, and guide patient prognosis and management with specific therapies.

[Efficacy of European Organization for Research and Treatment of Cancer (EORTC) risk tables for the prediction of recurrence and progression of non-muscle invasive bladder cancer after intravesical pirarubicin instillation].

OBJECTIVE: To analyze the influence of intravesical Pirarubicin (THP) instillation on the prediction results of European Organization for Research and Treatment of Cancer (EORTC) risk tables and to discuss the efficacy of EORTC risk tables in clinical application. METHODS: We retrospectively reviewed the clinical data of 389 patients with non-muscle invasive bladder cancer after TURBT treated with intravesical pirarubicin instillation. According to the EORTC Scoring System, all the cases were divided into low risk group, intermediate risk group and high risk group. The 1-year and 5-year recurrence and progression rates of each group were calculated and compared with the prediction results of the EORTC risk tables. RESULTS: The 1-year recurrence and progression rates of the low risk group were 8.0% and 0, those of the intermediate risk group were 31.0% and 2.8%, and those of the high risk group were 52.5% and 18.6%, respectively. The 5-year recurrence and progression rates of low risk group were 16.0% and 5.3%, those of the intermediate risk group were 42.6% and 10.7%, and those of the high risk group were 63.9% and 41.9%, respectively. The prediction results of progression rate were similar to that of the EORTC risk tables while the overall recurrence rate was lower. CONCLUSIONS: The EORTC risk tables can be effectively used to predict the recurrence rate and progression rate of non-muscle invasive bladder cancer. However, the EORTC risk tables have a tendency to overestimate the recurrence rate. Intravesical pirarubicin instillation is helpful to reduce the recurrence rate, yet has no obvious influence on the tumor progression.

Influence of clinical characteristics and tumor size on symptoms of bladder leiomyoma: a pooled analysis of 61 cases.

BACKGROUND: Bladder leiomyoma is an uncommon type of bladder neoplasms. Most publications are reports of isolated cases. The influence of tumor size on patients' early symptoms was seldom analyzed. We aim to investigate the clinical characteristics of bladder leiomyoma and the influence of tumor size on patients'symptoms in Chinese population. METHODS: We reviewed the medical records of eight patients diagnosed with bladder leiomyoma at our department, collected 53 cases from Chinese National Knowledge Infrastructure (CNKI), Wangfang data base, and Chinese Biological Medicine Disk, and performed a pooled analysis. The clinical characteristics of the patients were analyzed and then classified into symptomatic and asymptomatic groups. The association between tumor size and the occurrence of symptoms was evaluated. Furthermore, Logistic regression model was constructed to discriminate variables. RESULTS: Women comprised the majority of the patients (49/61, 80.3%). The mean age and tumor size were (42.3 ± 14.0) years and (45.0 ± 25.7) mm, respectively. Among all the symptoms, irritative symptoms occurred most frequently (37.7%, 23/61), followed by obstructive urinary symptoms (31.1%, 19/61), hematuria (24.6%, 15/61), and abdominal bulge or pain (14.8%, 9/61). In our study, patients who were 45 years old or younger tended to be asymptomatic compared with elder ones (14/36 vs. 3/25, P = 0.021). The histological, as well as anatomical, location of tumor, did not show significant differences between symptomatic and asymptomatic patients (P = 0.306 and 0.700). Tumors larger than 30 mm in the greatest diameter would cause clinical symptoms such as obstructive urinary symptoms (P = 0.048) and irritative symptoms (P = 0.037). Logistic regression confirmed the association between tumor size and the occurrence of symptoms, which was related with age. CONCLUSIONS: Bladder leiomyoma occurs mainly in women and most frequently with irritative symptoms. The occurrence of symptoms is related to tumor size rather than the location. In this setting, patients with endovesical tumors smaller than 30 mm in the greatest diameter tended to be asymptomatic, which were usually treated with transurethral resection of bladder tumor.

Clinical characteristics of bladder urothelial tumors in male patients--the influences of benign prostatic hyperplasia/benign prostatic enlargement.

OBJECTIVES: To investigate the clinical characteristics of bladder urothelial tumors in male patients. PATIENTS AND METHODS: The clinical characteristics of 356 patients with newly diagnosed bladder urothelial tumors from July 2005 to January 2010 were analyzed. Characteristics of different age groups were compared. Furthermore, tumor characteristics were analyzed to define the relationship, if any, with benign prostatic hyperplasia/benign prostatic enlargement. RESULTS: For bladder urothelial tumors, the percentage of carcinoma increased significantly with increasing age (P < 0.001), and differences were found among 3 age groups in the distribution of high grade carcinoma (P = 0.012). Especially in non-muscle-invasive carcinoma, the percentage of high grade carcinoma increased significantly with increasing age (P = 0.006), with significant differences between the ≤50 years group and the 51-69 years group and ≥70 years group (P = 0.031, P = 0.002). Interestingly, compared with non-benign prostatic hyperplasia/benign prostatic enlargement patients, benign prostatic hyperplasia/benign prostatic enlargement patients were more frequently diagnosed with poorly differentiated tumors, and logistic regression confirmed associations between benign prostatic hyperplasia/benign prostatic enlargement and unfavorable carcinoma, controlling for age (P = 0.009). CONCLUSIONS: Age is an unfavorable influence on the clinical characteristics of bladder urothelial tumors in men, and it was observed that the percentage of unfavorable tumors increased with age. Interestingly, noticeable changes of tumor differentiation appeared at the age of 50 years, and it was indicated that the natural history of carcinoma appeared to differ according to benign prostatic hyperplasia/benign prostatic enlargement statuses. There was a tendency for the men, who were diagnosed with benign prostatic hyperplasia/benign prostatic enlargement, to present with unfavorable carcinoma.

[Safety of solifenacin and tolterodine in the treatment of overactive bladder: a meta-analysis].

OBJECTIVE: To evaluate the safety of solifenacin and tolterodine in the treatment of overactive bladder (OAB). METHODS: Studies on the solifenacin, tolterodine and OAB were searched and those fulfilling the inclusion criteria were selected. RevMan 5.0 software was used to perform meta-analysis. Three studies were included with an overall sample size of 1013 cases. The experimental group of solifenacin contained 517 cases while the control group had 496 cases. RESULTS: The incidence rates of overall adverse event, dry mouth, constipation and blurred vision of the experimental group (solifenacin 5 mg once per day) was 26.69% (138/517), 10.64% (55/517), 5.42% (28/517) and 6.55% (26/397) while those of the control group (tolterodine 2 mg twice per day) 33.27% (165/496), 16.73% (83/496), 2.22% (11/496) and 4.20% (16/381) respectively. There was no statistically significant difference in overall adverse event (RR = 0.76, 95%CI: 0.52 - 1.12, P = 0.170) and blurred vision (RR = 1.59, 95%CI: 0.88 - 2.90, P = 0.130) between two groups. However, the incidence rate of key antimuscarinic adverse events such as dry mouth (RR = 0.63, 95%CI: 0.46 - 0.87, P = 0.005) and constipation (RR = 2.38, 95%CI: 1.21 - 4.66, P = 0.010) showed statistically significant difference. CONCLUSIONS: Dry mouth is the most common adverse event of solifenacin (5 mg once per day) and tolterodine (2 mg twice per day). Solifenacin has a lower incidence rate of dry mouth and a higher rate of constipation than tolterodine. A clinical physician should consider the incidence of adverse events during treating OAB, especially for those patients prone to constipation.