[Influence of Renin-angiotensin System Blockage on Recurrence of Non-muscle-invasive Bladder Cancer].

OBJECTIVE: To investigate the effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) on the recurrence of non-muscle-invasive bladder cancer (NMIBC). METHODS: Clinical data of 388 patients with NMIBC undergoing transurethral resection of bladder tumor during Jan. 2009 to Dec. 2011 were retrospectively reviewed. Recurrence-free survival was analyzed, and the risk factors of recurrence were explored by Cox multivariate regression analysis. RESULTS: All patients were managed with postoperative intravesical chemotherapy, but 82 of them only received maintenance instillation without immediate instillation. There were 161 patients diagnosed of hypertension, 107 of them were treated with ACEIs or ARBs. No significant differences in age, sex, history of smoking, pathological stage, pathological grade, tumor diameter and post-operation immediate instillation were observed between the patients treated with (drug-use group) or without ACEIs/ARBs (control group). There was also no statistically significant difference among aforementioned indexes after the stratification by hypertension and medication (ACEIs/ARBs). During a median follow up of 60 months, there were 36 and 129 patients found recurrence in drug-use group and control group, respectively. The recurrence free survival times of the patients treated with and without ACEIs/ARBs were (48.43±23.50) and (41.15±23.64) months, respectively (P=0.007). The 5-year recurrence-free survival rate was 66.36% in drug-use group and 54.09% in the controls (P=0.027). Multivariate regression analysis revealed that no ACEIs/ARBs treatment [standardized regression coefficient (ß) =0.174] was independent risk factor of recurrence (P<0.05). The weight of no ACEIs/ARBs treatment was behind to no immediate instillation (ß=0.131), tumor multiplicity (ß=0.128), tumor diameter ≥3 cm (ß=0.193), grade 3 tumor (ß=0.181), and smoking status (ß=0.191). CONCLUSION: Theadministration of ACEIs/ARBs may decrease the recurrence of NMIBC after transurethral resection of bladder tumor.

[Detection of Circulating Tumor Cells in Bladder Cancer by Subtraction Enrichment and Immunostaining-fluorescence in situ Hybridization].

OBJECTIVE: To detect circulating tumor cells (CTCs) in peripheral blood from the patients with bladder cancer using subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH) and to explore the relation between CTCs detection result and the clinicpathological parameters of tumors. METHODS: Sixteen patients [(66.88±8.97) yr.] with bladder cancerwere included, whlile 10 normal people [(61.90±9.13) yr.] were enrolled as control. Peripheral blood was harvested (6 mL per case) for the detection of CTCs with the method of subtraction enrichment and SE-iFISH, and the correlations of CTCs level to the clinicpathological parameters of tumors were analyzed, including hematuria, size, number, NMIBC or MIBC, stage, grade and pathological type. RESULTS: Positive rates of CTCs in experimental and control group were 43.75% (7/16) and 0% (0/10), respectively. The difference was statistically significant (P=0.022 7). The number of CTCS was not associated with the clinicpathological parameters of bladder cancer, which probably due to small sample size. CONCLUSION: It is applicable to detect CTCs of bladder cancer by SE-iFISH.

[Bladder reconstruction using autologous bone marrow mesenchyaml stem cells-seeded bladder acellelar matrix graft in a canine model].

OBJECTIVE: To investigate the feasibility of autologous bone marrow mesenchymal stem cells(BMSCs) seeded on bladder acellular matrix graft (BAMG) for bladder reconstruction in a canine model. METHODS: This study included 25 mongrel dogs. Five dogs were sacrificed for the preparation of BAMG. Twenty dogs were randomly divided into two groups and received partial cystectomy. In group A, the bladder defect was repaired with unseeded BAMG. In group B, the bladder defect was repaired with autologous BMSCs-seeded BAMG. The bladders were retrieved and studied histologically and immunohistochemically at the time point of 1, 2, 4, 8, 12 weeks after surgery to evaluate tissue regeneration. RESULTS: All dogs survived the procedure. Histopathological examination in group B showed there was urothelium developed at the end of the 2 weeks. By 8 and 12 weeks all bladder wall components were regenerated in the repaired area, which were similar to normal bladder tissue. In group A, urothelium regeneration was observed at the end of the 4 weeks, whereas smooth muscle was still not well-formed by 12 weeks. CONCLUSION: Autologous BMSCs-seeded BAMG could promote the repair of bladder defect, which is superior to unseeded BAMG in regenerative properties.

Efficacy and safety of antibody-drug conjugates in the treatment of urothelial cell carcinoma: a systematic review and meta-analysis of prospective clinical trials.

Introduction: Urothelial carcinoma (UC) is a refractory disease for which achieving satisfactory outcomes remains challenging with current surgical interventions. Antibody-drug conjugates (ADCs) are a novel class of targeted therapeutics that have demonstrated encouraging results for UC. Although there is a limited number of high-quality randomized control trials (RCTs) examining the use of ADCs in patients with UC, some prospective non-randomized studies of interventions (NRSIs) provide valuable insights and pertinent information. We aim to assess the efficacy and safety of ADCs in patients with UC, particularly those with locally advanced and metastatic diseases. Methods: A systematic search was conducted across PubMed, Embase, the Cochrane Library, and Web of Science databases to identify pertinent studies. Outcomes, such as the overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), adverse events (AEs), and treatment-related adverse events (TRAEs), were extracted for further analyses. Results: Twelve studies involving 1,311 patients were included in this meta-analysis. In terms of tumor responses, the pooled ORR and DCR were 40% and 74%, respectively. Regarding survival analysis, the pooled median PFS and OS were 5.66 months and 12.63 months, respectively. The pooled 6-month PFS and OS were 47% and 80%, while the pooled 1-year PFS and OS were 22% and 55%, respectively. The most common TRAEs of the ADCs were alopecia (all grades: 45%, grades ≥ III: 0%), decreased appetite (all grades: 34%, grades ≥ III: 3%), dysgeusia (all grades: 40%, grades ≥ III: 0%), fatigue (all grades: 39%, grades ≥ III: 5%), nausea (all grades: 45%, grades ≥ III: 2%), peripheral sensory neuropathy (all grades: 37%, grades ≥ III: 2%), and pruritus (all grades: 32%, grades ≥ III: 1%). Conclusion: The meta-analysis in this study demonstrates that ADCs have promising efficacies and safety for patients with advanced or metastatic UC. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42023460232.

Sleep and circadian rhythm disturbance in kidney stone disease: a narrative review.

The circadian rhythm generated by circadian clock genes functions as an internal timing system. Since the circadian rhythm controls abundant physiological processes, the circadian rhythm evolved in organisms is salient for adaptation to environmental change. A disturbed circadian rhythm is a trigger for numerous pathological events. Recently, accumulated data have indicated that kidney stone disease (KSD) is related to circadian rhythm disturbance. However, the mechanism between them has not been fully elucidated. In this narrative review, we summarized existing evidence to illustrate the possible association between circadian rhythm disturbance and KSD based on the epidemiological studies and risk factors that are linked to circadian rhythm disturbance and discuss some chronotherapies for KSD. In summary, KSD is associated with systemic disorders. Metabolic syndrome, inflammatory bowel disease, and microbiome dysbiosis are the major risk factors supported by sufficient data to cause KSD in patients with circadian rhythm disturbance, while others including hypertension, vitamin D deficiency, parathyroid gland dysfunction, and renal tubular damage/dysfunction need further investigation. Then, some chronotherapies for KSD were confirmed to be effective, but the molecular mechanism is still unclear.

Application of metabolomics in urolithiasis: the discovery and usage of succinate.

Urinary stone is conceptualized as a chronic metabolic disorder punctuated by symptomatic stone events. It has been shown that the occurrence of calcium oxalate monohydrate (COM) during stone formation is regulated by crystal growth modifiers. Although crystallization inhibitors have been recognized as a therapeutic modality for decades, limited progress has been made in the discovery of effective modifiers to intervene with stone disease. In this study, we have used metabolomics technologies, a powerful approach to identify biomarkers by screening the urine components of the dynamic progression in a bladder stone model. By in-depth mining and analysis of metabolomics data, we have screened five differential metabolites. Through density functional theory studies and bulk crystallization, we found that three of them (salicyluric, gentisic acid and succinate) could effectively inhibit nucleation in vitro. We thereby assessed the impact of the inhibitors with an EG-induced rat model for kidney stones. Notably, succinate, a key player in the tricarboxylic acid cycle, could decrease kidney calcium deposition and injury in the model. Transcriptomic analysis further showed that the protective effect of succinate was mainly through anti-inflammation, inhibition of cell adhesion and osteogenic differentiation. These findings indicated that succinate may provide a new therapeutic option for urinary stones.

Prognostic value of preoperative neutrophil-to-lymphocyte ratio in histological variants of non-muscle-invasive bladder cancer.

PURPOSE: Many studies identified that the preoperative neutrophil-to-lymphocyte ratio (PNLR) was associated with patient prognosis in non-muscle-invasive bladder cancer (NMIBC). We hypothesized that PNLR could be prognostic in patients with histological variants of NMIBC (VH-NMIBC). MATERIALS AND METHODS: This retrospective study included patients with VH-NMIBC admitted at our center between January 2009 and May 2019. The best cut-off value of NLR was measured by the receiver operating characteristic curve and Youden index. The Kaplan-Meier method and Cox proportional hazard regression models were employed to evaluate the association between PNLR and disease prognosis, including recurrence-free survival (RFS), progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). RESULTS: A total of 243 patients with VH-NMIBC were enrolled in our study. According to the Kaplan-Meier method results, patients with PNLR ≥2.2 were associated with poor RFS (p<0.001), PFS (p<0.001), CSS (p<0.001), and OS (p<0.001). Multivariable analyses indicated that PNLR ≥ 2.2 was an independent prognostic factor of RFS (hazard ratio [HR], 2.11; 95% confidence interval [CI, 1.57-1.83; p<0.001), PFS (HR, 2.34; 95% CI, 1.70-3.21; p<0.001), CCS (HR, 2.87; 95% CI, 1.96-4.18; p< 0.001), and OS (HR, 2.83; 95% CI, 1.96-4.07; p<0.001). CONCLUSIONS: This study identified that PNLR ≥2.2 was usually associated with a poor prognosis for patients with VH-NMIBC.

Urethral diverticular with broadly squamous metaplasia in a patient with urethral diverticular calculi: A case report.

RATIONALE: There are already several reports concerning the occurrence of urethral diverticulum (UD) in female patients, but only rarely has a article describing UD combined with UD calculi or squamous carcinoma been published. Moreover, a case with squamous carcinoma and UD calculi at the same time has never been reported, making this the first case report about this condition. PATIENT CONCERNS: A 43-year-old woman presented to the gynaecology department with a complaint of a hard mass beneath the anterior vaginal wall. DIAGNOSES: Transvaginal ultrasound (TVU) revealed a UD. INTERVENTIONS: We performed a standard urethral diverticular excision. Intraoperatively, we identified and removed a stone from the diverticulum. The intraoperative finding of a stone challenged the diagnosis of UD, with subsequent histological examination of biopsy tissue from the mass demonstrating broadly squamous metaplasia. OUTCOMES: The broadly squamous metaplasia predominantly originated from the stone, and the stone was entirely removed. No complications occurred during the whole follow-up period. Moreover, after the 12-month follow-up, there was no diverticular recurrence or carcinoma metastasis. LESSONS: UD calculi may be considered a risk factor for female urethra squamous metaplasia, which with the potential of squamous carcinoma, so patients will be advised to treat this condition immediately.

Alcohol intake and risk of erectile dysfunction: a dose-response meta-analysis of observational studies.

The purpose of the present study was to conduct a meta-analysis of cross-sectional studies assessing the relationship between alcohol consumption and the risk of erectile dysfunction (ED). To identify relevant studies, databases such as Pubmed, Medline, Embase, and the Cochrane Library were searched from the inception of the present study to March 2016. Finally, 24 studies (154,295 patients) were included. We combined a study-specific odds ratio (OR) estimated by using a random effects meta-analysis. The results of our meta-analysis indicated that light to moderate alcohol consumption (<21 drinks/week) was correlated with a decreased risk of erectile dysfunction (OR = 0.71; 95% CI: 0.59-0.86; P = 0.000). However, regular (ever vs. never) and high alcohol consumption (>21 drinks/week) had no significant influence on the prevalence of ED (regular: OR = 0.87; 95% CI: 0.75-1.07; P = 0.062; high: OR = 0.99; 95% CI: 0.80-1.22; P = 0.893). In a dose-response meta-analysis, a non-linear relationship was observed between alcohol consumption and risk of ED (P for non-linearity = 0.0000). In conclusion, moderate intake of alcohol exhibited a beneficial effect on the risk of ED, whereas regular and high consumption did not.