Benkang Shi

Safety and efficacy of holmium laser resection for primary nonmuscle-invasive bladder cancer versus transurethral electroresection: single-center experience.

OBJECTIVES To assess the safety and efficacy of holmium laser resection for primary, clinically nonmuscle-invasive, bladder cancer (HoLRBT) compared with standard transurethral resection of bladder tumor (TURBT). METHODS The data from a total of 212 consecutive patients with primary nonmuscle-invasive bladder cancer were collected in this study. These patients were treated by holmium laser resection (HoLRBT group) or transurethral electroresection (TURBT group) and were divided into 2 groups. The patients in each group were stratified into 3 risk subgroups (low, intermediate, and high risk) according to the prognostic factors for recurrence using the European Association of Urology guidelines. The intraoperative complications and postoperative characteristics of the HoLRBT and TURBT groups were compared. Efficacy, indicated by the recurrence-free survival in the overall group and stratified subgroups, was analyzed and compared using the Kaplan-Meier technique and the log-rank test. RESULTS The patient demographics and tumor characteristics in the 2 groups were comparable. HoLRBT was superior to TURBT in terms of intraoperative complications and postoperative catheterization time (P < .001). Recurrence-free survival after HoLRBT was similar to that after TURBT (P = .283). CONCLUSIONS Our results have indicated that HoLRBT is a feasible, safe, and effective alternative for the management of primary, clinically nonmuscle-invasive, bladder cancer compared with TURBT, with similar recurrence-free survival and fewer perioperative complications. It also can provide sufficient material for the pathologic evaluation.

Incidence and Risk of Sorafenib‐Induced Hypertension: A Systematic Review and Meta‐Analysis

Hypertension is one of the major side effects of sorafenib, and reported incidences vary substantially among clinical trials. A systematic review was conducted using Medline, PubMed, Embase, and the Cochrane Library for all longitudinal studies to investigate the incidence and risk of hypertension events in cancer patients treated with sorafenib. A total of 14 randomized controlled trials and 39 prospective single‐arm trials involving 13,555 patients were selected for the meta‐analysis. The relative risk of all‐grade and high‐grade hypertension associated with sorafenib were 3.07 (95% confidence interval [CI], 2.05–4.60; P<.01) and 3.31 (95% CI, 2.21–4.95; P<.01), respectively. The overall incidence of sorafenib‐induced all‐grade and high‐grade hypertension were 19.1% (95% CI, 15.8%–22.4%) and 4.3% (95% CI, 3.0%–5.5%), respectively. A significantly higher incidence of hypertension was noted in patients with renal cell carcinoma (RCC) compared with those with non‐RCC malignancies (all‐grade: 24.9% [95% CI, 19.7%–30.1%] vs 15.7% [95% CI, 12.1%–19.3%]; P<.05; high‐grade:8.6% [95% CI, 6.0%–11.2%] vs 1.8% [95% CI, 0.9%–2.6%]; P<.05). The trials with median progression‐free survival (PFS) longer than 5.3 months (mean PFS) demonstrated a significantly higher incidence of high‐grade hypertension than trials with shorter PFS (6.3% [95% CI, 4.1%–8.5%] vs 2.6% [95% CI, 1.4%–3.8%]; P<.05). Findings of the meta‐analysis indicated a significantly high risk of sorafenib‐induced hypertension. Patients with RCC have a significantly higher incidence of hypertension and the occurrence of hypertension may be associated with improved prognosis.

Relationship Between Patient Age and Superficial Transitional Cell Carcinoma Characteristics

OBJECTIVES To evaluate the relationship between patient age and the characteristics of superficial transitional cell carcinoma. METHODS The clinical and pathologic records of 576 patients were retrospectively reviewed. The patients were classified into three groups: those 40 years or younger, those 41 to 59 years old, and those 60 years or older. The transitional cell carcinoma characteristics of three groups were analyzed to define the relationship, if any, with age. RESULTS The male/female ratio was 4.1:1, 3.6:1, and 2.3:1 in the three age groups, with significant differences between the 60 years or older group and the 40 years or younger group and 41 to 59 year group (P <0.05). The percentage of patients with poorly differentiated tumor increased with increasing age, and a significant difference was found between the 60 years or older group and the 40 years or younger and 41 to 59 year groups (P <0.05). The overall recurrence rate was 34.2% at 12 months and 40.8% at 24 months. The nonrecurrence rate was significantly greater in those 40 years or younger compared with those 60 years or older in all three risk groups (P <0.05). CONCLUSIONS The results of our study have shown that the percentage of female patients with bladder cancer increases with increasing age and that elderly patients are more likely to present with poorly differentiated bladder cancer. Also, the recurrence-free survival rate decreased with increasing age.

Y-27632 improves the erectile dysfunction with ageing in SD rats through adjusting the imbalance between nNo and the Rho-kinase pathways.

We investigated whether the effect of Y‐27632 to improve the erectile function in SD rats was associated with the degree of the imbalance between nNOS and the Rho‐kinase pathways. Western blot analysis was used to evaluate nNOS and Rho‐kinase protein expression in 10 young and 10 old SD rats. Imbalance value between nNOS and Rho‐kinase protein levels was obtained by subtracting nNOS from Rho‐kinase. A 5‐V stimulus was given in SD rats before and after the administration of 200 nmol kg−1 of Y‐27632 intracavernosally and ICP/MAP was recorded. The improvement of erectile function induced by Y‐27632 was expressed as the margin of ICP/MAP after and before the administration of Y‐27632. In young rat group, the contents of nNOS and Rho‐kinase protein were 1.7 ± 0.15 and 1.8 ± 0.14 respectively. In old rat group, the nNOS protein decreased to 1 ± 0.15, and in contrast, the Rho‐kinase protein increased to 2.6 ± 0.2. The imbalance value between nNOS and Rho‐kinase was 0.2986 ± 0.1109 and 1.5961 ± 0.1206 in young and old rat groups. The improvement of erectile function induced by Y‐27632 was 0.0500 ± 0.0294 and 0.3420 ± 0.660 in young and old rat groups. In all rats, the correlation coefficient between the imbalance value of nNOS and Rho‐kinase and the improvement of erectile function was 0.649, P < 0.01. In conclusion, this study suggested that impaired erectile function with ageing in SD rats be associated with the imbalance between nNO and Rho‐kinase activity and Y‐27632 could improve the erectile function in old SD rats through adjusting this imbalance.

Grape Seed Proanthocyanidin Extract Ameliorates Diabetic Bladder Dysfunction via the Activation of the Nrf2 Pathway.

Diabetes Mellitus (DM)-induced bladder dysfunction is predominantly due to the long-term oxidative stress caused by hyperglycemia. Grape seed proanthocyanidin extract (GSPE) has been reported to possess a broad spectrum of pharmacological and therapeutic properties against oxidative stress. However, its protective effects against diabetic bladder dysfunction have not been clarified. This study focuses on the effects of GSPE on bladder dysfunction in diabetic rats induced by streptozotocin. After 8 weeks of GSPE administration, the bladder function of the diabetic rats was improved significantly, as indicated by both urodynamics analysis and histopathological manifestation. Moreover, the disordered activities of antioxidant enzymes (SOD and GSH-Px) and abnormal oxidative stress levels were partly reversed by treatment with GSPE. Furthermore, the level of apoptosis in the bladder caused by DM was decreased following the administration of GSPE according to the Terminal Deoxynucleotidyl Transferase (TdT)-mediated dUTP Nick-End Labeling (TUNEL) assay. Additionally, GSPE affected the expression of apoptosis-related proteins such as Bax, Bcl-2 and cleaved caspase-3. Furthermore, GSPE showed neuroprotective effects on the bladder of diabetic rats, as shown by the increased expression of nerve growth factor (NGF) and decreased expression of the precursor of nerve growth factor (proNGF). GSPE also activated nuclear erythroid2-related factor2 (Nrf2), which is a key antioxidative transcription factor, with the concomitant elevation of downstream hemeoxygenase-1 (HO-1). These findings suggested that GSPE could ameliorate diabetic bladder dysfunction and decrease the apoptosis of the bladder in diabetic rats, a finding that may be associated with its antioxidant activity and ability to activate the Nrf2 defense pathway.

Bone Marrow Mesenchymal Stem Cells Induce Angiogenesis and Promote Bladder Cancer Growth in a Rabbit Model

Objectives: To investigate the effect of mesenchymal stem cells (MSCs) in the process of tumor development and the possibility of MSCs differentiating into vascular endothelial cells in the tumor microenvironment. Material and Methods: Twenty male New Zealand rabbits were randomly divided into 2 groups: a test group and a control group. MSCs were isolated and cultured by bone marrow cell adherence. The bladder tumor models were built by embedding a VX2 mass in swelled bladder mucosa in all of the rabbits (n = 20). One week later, 4′,6-diamidino-2-phenylindole-labeling MSCs were transplanted into tumor tissue in the test group (n = 10). Culture medium was injected into the tumor tissue of the control group (n = 10). The maximum diameter of the tumor mass was measured by ultrasound at 2 and 4 weeks after the VX2 tumor mass was embedded. All animals were sacrificed at 4 weeks. The double labeling immunofluorescence for CD146 was performed to reveal whether engrafted cells can differentiate into vascular endothelial cells. Vascular density was compared between the 2 groups. Results: There was no significant difference in the maximum diameters of the tumor masses between the 2 groups at 2 weeks (test group 0.77 ± 0.15 cm vs. control group 0.71 ± 0.15 cm, p > 0.05). The maximum diameters appeared larger in the test group at 4 weeks (test group 3.82 ± 0.94 cm vs. control group 2.28 ± 0.54 cm, p < 0.05). Immunofluorescence studies revealed some engrafted MSCs expressing a vascular endothelial cell phenotype (CD146). Furthermore, vascular density was augmented in the test group in comparison to the control group (10.1 ± 0.70/0.2 mm2 vs. 8.24 ± 0.81/0.2 mm2, p < 0.05). Conclusions: Engrafted MSCs can differentiate into vascular endothelial cells and contribute to angiogenesis in the tumor microenvironment, which may be the major pathway of promoting tumor growth.

E-Cadherin Tissue Expression and Urinary Soluble Forms of E-Cadherin in Patients with Bladder Transitional Cell Carcinoma

Objective: To investigate the clinical significance of E-cadherin (E-CD) expression in human bladder transitional cell carcinoma (TCC) tissue and soluble forms of E-cadherin (sE-CD) in the urine of patients with TCC. Materials and Methods: One hundred and two specimens of bladder TCC and 10 normal bladder tissues were stained immunohistochemically with anti-E-CD monoclonal antibody. The urinary sE-CD from 59 subjects with TCC or controls was measured with enzyme-linked immunosorbent assay (ELISA). All results were analyzed statistically between groups. Results: The expression of E-CD in bladder TCC correlated well with grade and stage but had no significant correlation with the size or number of the tumors. Normal expression rate of E-CD is significantly higher in primary than in recurrent tumors. The level of urinary sE-CD was higher in patients with TCC than in normal controls or patients with benign disorders of the urinary system. Urinary sE-CD levels were strongly correlated with tumor grade but showed no significant correlation with the stage, size and number of the tumors. The urinary sE-CD level is significantly higher in the recurrent group than in the primary group. Conclusions: Expression of E-CD in the tissue of TCC and the urinary level of sE-CD are very closely associated with the biological behaviors of bladder TCC.

Increased expression of miR-222 is associated with poor prognosis in bladder cancer

BackgroundMicroRNA-222 (miR-222) has been shown to play a potential oncogenic role in bladder cancer. The aim of this study was to evaluate the expression of miR-222 in bladder cancer and its potential relevance to clinicopathological characteristics and patient survival.MethodsSurgical specimens of cancer tissue and adjacent normal tissue were obtained from 97 patients with bladder cancer. The relative expression levels of miR-222 in the cancer and the normal adjacent tissue were measured by quantitative reverse-transcriptase PCR. We analyzed their correlation with clinicopathological parameters and prognostic value.ResultsThe expression level of miR-222 was significantly higher in tumor tissues than in corresponding non-cancerous tissues (5.46 ± 1.45 versus 1.92 ± 0.65, P < 0.0001), and a high expression of miR-222 was found to be significantly associated with tumor grade (P = 0.003) and tumor stage (P = 0.005). The miR-222 expression level was classified as high or low in relation to the median value (cutoff value = 5.15). Kaplan-Meier analysis showed that patients with higher levels of miR-222 had significantly poorer survival than those with lower expression of this miRNA in patients, with a 5-year overall survival of 29.53% and 52.75%, respectively (P = 0.0034). In the multivariate Cox proportional hazards analysis, which included miR-222 level, tumor grade, tumor stage, and tumor number, high miR-222 expression was independently associated with poor survival (P < 0.001; hazard ratio 6.17; 95% CI 2.33 to 10.39).ConclusionmiR-222 overexpression is involved in the poor prognosis of bladder cancer and can be used as a biomarker for selection of cases requiring special attention.

The clinical characteristics of renal cell carcinoma in female patients.

Objective:  To investigate the clinical characteristics of renal cell carcinoma (RCC) in female patients.

Alterations of Urine TGF-β1 and bFGF following Bladder Outlet Obstruction: A Predictor for Detrusor Contractibility?

Objectives: To investigate the alterations of urine transforming growth factor-β1 (TGF-β1) and basic fibroblast growth factor (bFGF) following bladder outlet obstruction (BOO) in rats and to determine their correlation with the impaired detrusor contractibility. Methods: Wistar rats were divided into control, 2-week BOO 6-week and BOO groups. Impaired detrusor contractibility was quantified by measuring detrusor contraction force (DCF) of detrusor strip stimulated by carbachol. The enzyme-linked immunosorbent assay method was used to determine the urine levels of the 2 factors. Correlation analysis was conducted between DCF and urine levels of the 2 factors to see if there was an association between them after BOO. Results: DCF was found to be significantly lower in the 6-week BOO group than in the 2-week BOO and control groups. There is no significant difference regarding urine TGF-β1 between the 2-week BOO and control groups (p > 0.05). Urine TGF-β1 level in the 6-week BOO group was significantly higher than in the 2-week BOO (p < 0.05) and control groups (p < 0.05). There existed a negative correlation between DCF and urine TGF-β1 (p < 0.05). Conclusions: In an animal model, our results have suggested the potential role of urine TGF-β1 as a noninvasive biomarker to predict detrusor contractibility after BOO.