Yaofeng Zhu

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.

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.

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.

Are TGF-β1 and bFGF Correlated with Bladder Underactivity Induced by Bladder Outlet Obstruction?

Background: Transforming growth factor-β1 (TGF-β1) and basic fibroblast growth factor (bFGF) are the two most important growth factors that have been found. Previous studies have indicated that the above two factors play an important role in the physiological growth, response to injury and the following fibrous proliferation of the bladder. Therefore, they may be related to the detrusor underactivity due to bladder outlet obstruction (BOO). The aim of this study is to investigate the relationship between them. Materials and Methods: 29 evaluable Wistar rats were divided into three groups: control group, BOO 2 weeks group and BOO 6 weeks group. After successful models, we measured excised bladder mass, detrusor contraction force (DCF) in vitro stimulated by carbachol of four different concentrations (10–5, 10–4, 10–3 and 10–2 mM). Simultaneously, the expression of TGF-β1 mRNA and bFGF mRNA in detrusor specimens was detected by reverse transcription polymerase chain reaction (RT-PCR) analysis. Additionally, we analyzed the correlation between DCF and the detrusor mRNA expression of the two factors to determine whether they are associated with the detrusor contraction response when BOO occurs. Results: Bladder mass increased steadily and significantly with the progression of the BOO. While at the point of 10–4 and 10–3 mM carbachol concentration, DCF in the BOO 2 weeks group was higher, no significant differences were found at the point of 10–5 and 10–2 mM carbachol concentration when compared to the control group. DCF was found to be significantly lower in the BOO 6 weeks group than in the BOO 2 weeks group and control group at all points of carbachol concentration. TGF-β1 mRNA expression of the detrusor was found to be higher only in BOO 6 weeks. However, there was a steady and significant increase of bFGF mRNA expression with the aggravation of BOO. Correlation analysis demonstrated that there was a significant moderate negative correlation between DCF in vitro and the level of TGF-β1 mRNA. Meanwhile, a significant high negative correlation was acquired between the DCF and bFGF mRNA level. Conclusion: DCF in the severe BOO group is remarkably impaired. There is a sustained rise of bFGF mRNA expression in detrusor with the progression of BOO, but TGF-β1 mRNA expression increase becomes evident only in the decompensation stage. Significant negative correlations are found between DCF in vivo and the expression of TGF-β1 mRNA, bFGF mRNA. Additionally, DCF correlates negatively with the bladder mass statistically after BOO.

Long‐term outcome following thulium vaporesection of the prostate

The continuous wave 2‐μm Thulium Laser has been introduced as potential technology with both high efficiency and safe practice; although little data have been shown regarding the long‐term outcomes.

Prognostic scores based on the preoperative plasma fibrinogen and serum albumin level as a prognostic factor in patients with upper urinary tract urothelial carcinoma

This study is to clarify the prognostic value of preoperative plasma fibrinogen and serum albumin level, as known as FA score, in a cohort of Chinese patients with upper urinary tract urothelial carcinoma (UTUC). We retrospectively evaluated clinicopathological data on 169 patients who underwent surgery between 2006 and 2013. The FA score was calculated based on cutoff values of 3.53g/L for fibrinogen and 43.56 g/L for albumin. Overall survival and cancer specific survival was assessed using the Kaplan-Meier method and the equivalences of the curves were tested by log-rank tests. The Cox proportional hazards regression model was applied in univariate and multivariate analyses. In univariate analysis, tumor size, tumor grade, pathological T stage and FA score were significantly associated with overall survival and cancer specific survival, and multivariate Cox proportional hazards regression analysis identified FA score (score 1: HR=3.486, 95%CI 1.358-8.948, p=0.009; HR=3.485, 95%CI 1.363-8.913, p=0.009, respectively; score 2: HR=5.509, 95%CI 2.144-14.158, p<0.001; HR=5.521, 95%CI 2.074-14.697, p=0.001, respectively) was an independent predictor for overall survival and cancer specific survival. The evaluation of preoperative FA score can be regarded as an independent prognostic factor for predicting overall survival and cancer specific survival in UTUC. The fibrinogen and albumin levels are low cost and easy accessibility in clinical practice.This study is to clarify the prognostic value of preoperative plasma fibrinogen and serum albumin level, as known as FA score, in a cohort of Chinese patients with upper urinary tract urothelial carcinoma (UTUC). We retrospectively evaluated clinicopathological data on 169 patients who underwent surgery between 2006 and 2013. The FA score was calculated based on cutoff values of 3.53g/L for fibrinogen and 43.56 g/L for albumin. Overall survival and cancer specific survival was assessed using the Kaplan-Meier method and the equivalences of the curves were tested by log-rank tests. The Cox proportional hazards regression model was applied in univariate and multivariate analyses. In univariate analysis, tumor size, tumor grade, pathological T stage and FA score were significantly associated with overall survival and cancer specific survival, and multivariate Cox proportional hazards regression analysis identified FA score (score 1: HR=3.486, 95%CI 1.358-8.948, p=0.009; HR=3.485, 95%CI 1.363-8.913, p=0.009, respectively; score 2: HR=5.509, 95%CI 2.144-14.158, p<0.001; HR=5.521, 95%CI 2.074-14.697, p=0.001, respectively) was an independent predictor for overall survival and cancer specific survival. The evaluation of preoperative FA score can be regarded as an independent prognostic factor for predicting overall survival and cancer specific survival in UTUC. The fibrinogen and albumin levels are low cost and easy accessibility in clinical practice.

Combination of Intravesical Chemotherapy and Bacillus Calmette-Guerin Versus Bacillus Calmette-Guerin Monotherapy in Intermediate- and High-risk Nonmuscle Invasive Bladder Cancer: A Systematic Review and Meta-analysis.

Abstract Urothelial carcinoma of the bladder has become a major cause of morbidity, mortality, and health-related costs. There is still no standard instillation therapy against bladder cancer. A meta-analysis was conducted to evaluate the efficacy and toxicity of adding chemotherapy to Bacillus Calmette–Guerin (BCG) in intermediate- and high-risk nonmuscle invasive bladder cancer (NMIBC). All randomized controlled trials (RCTs) that evaluated the efficacy of combination therapy and BCG monotherapy for intermediate- and high-risk NMIBC were comprehensively searched. Relevant databases, including PubMed, Embase, Cochrane Central Register of Controlled trials databases, and American Society of Clinical Oncology (http://www.asco.org/ASCO), the clinical trial registration website (ClinicalTrials.gov), and relevant trials from the references of selected studies were searched from initial state up to June 6, 2015. Random-effects model was used to estimate hazard ratios (HRs) statistics. All statistical analyses were performed by STATA (version 13.0, College Station, TX). Seven studies, including 1373 patients with intermediate- and high-risk NMIBC, were identified. For disease-free survival, the pooled HRs from all studies was 0.69 (95% confidence interval [CI], 0.48–1.00; P = 0.048). The disease-free survival benefit was more apparent among patients with intermediate-risk NMIBC (P = 0.002) or Ta/T1 with/without carcinoma in situ (P < 0.01). In subgroup analysis, a significant reduction in recurrence was found in studies that explored the influence of a perioperative single dose instillation compared with delayed BCG monotherapy (HR = 0.60; 95% CI, 0.38–0.92; P = 0.021). No significant difference was found for progression-free survival (HR = 0.78; 95% CI, 0.43–1.44; P = 0.435). Patients with intermediate- and high-risk NMIBC who underwent combination therapy achieved lower rates of recurrence than those who underwent BCG therapy alone. No difference in progression-free survival was found between the 2 different therapy schedules. Better efficacy for a perioperative single dose instillation compared with delayed BCG monotherapy was found in this meta-analysis.