Influence of American Society of Anesthesiologists Score on Oncologic Outcomes in Patients With Upper Tract Urothelial Carcinoma After Radical Nephroureterectomy: A Large-Sample Study in Two Institutions.

INTRODUCTION: As a research team of urologists and an anesthetist, we sought to investigate the prognostic significance of American Society of Anesthesiologists (ASA) score in patients with upper tract urothelial cancer (UTUC) after radical nephroureterectomy (RNU). ASA physical status (ASA-PS) classification not only was found to be associated with increased comorbidities but also independently factors for predicting morbidity and mortality. Accurate risk assessment was being particularly important for patients being considered for surgery. METHODS: Records for 958 patients with UTUC who underwent RNU were reviewed. Clinicopathologic variables, including ASA-PS, were assessed at two institutions. Overall survival (OS), cancer-specific survival (CSS), intravesical recurrence-free survival (IRFS), and metastasis-free survival (MFS) were estimated using the Kaplan-Meier method and Cox regression analyses. We measured the independent predictive value of ASA-PS for mortality by multivariate regression. Association of ASA-PS and clinicopathologic variables was assessed. RESULTS: The group of patients with ASA = 2/3 had a shorter 5-year OS (67.6% and 49.9%), CSS (72.9% and 58.1%), and MFS (75.1% and 58.5%). The median follow-up time was 39 months. Kaplan-Meier curves showed that the group with ASA = 2/3 had significantly poorer OS, CSS, and MFS. Adjusting for multiple potential confounding factors, multivariate analyses suggested that ASA score was an independent predictor of OS, CSS, and MFS (p = 0.004, p = 0.005, p < 0.001). CONCLUSION: Higher ASA scores were independently associated with lower survival rate. This capability, along with its simplicity, makes it a valuable prognostic metric. It should be seriously referenced in UTUC patients being considered for RNU.

Hypoxia-Induced Autophagy Enhances Cisplatin Resistance in Human Bladder Cancer Cells by Targeting Hypoxia-Inducible Factor-1α.

PURPOSE: To investigate the effect of hypoxia on chemoresistance and the underlying mechanism in bladder cancer cells. METHODS: BIU-87 bladder cancer cell line was treated with cisplatin under hypoxic and normoxic conditions and tested using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, and Western blotting. All the data were expressed as mean ± standard error from three independent experiments and analyzed by multiple t-tests. RESULTS: Apoptosis of bladder cancer cells caused by cisplatin was attenuated in hypoxic conditions. Hypoxia enhanced autophagy caused by cisplatin. The autophagy inhibitor and HIF-1α inhibitor can reverse the chemoresistance in hypoxic condition. Apoptosis and autophagy of bladder cancer cells were downregulated by HIF-1α inhibitor YC-1. Hypoxia-induced autophagy enhanced chemoresistance to cisplatin via the HIF-1 signaling pathway. CONCLUSION: Resistance to cisplatin in BIU-87 bladder cancer cells under hypoxic conditions can be explained by activation of autophagy, which is regulated by HIF-1α-associated signaling pathways. The hypoxia-autophagy pathway may be a target for improving the efficacy of cisplatin chemotherapy in bladder cancer.

The Clinical Efficacy and Safety of Flexible Ureteroscopic Treatment for Parapelvic Renal Cyst and Secondary Renal Stone.

PURPOSE: To explore the efficacy and safety of flexible ureteroscopic incision and drainage and flexible ureteroscopic lithotripsy for treatment of parapelvic renal cyst combined with secondary renal stone. MATERIALS AND METHODS: 28 patients with parapelvic renal cyst combined with renal stone were treated with flexible ureteroscopic incision and drainage and flexible ureteroscopic lithotripsy simultaneously from May 2010 to December 2016. The follow-up was made 1, 3, 6?12 months and 2 years after surgical treatment in our outpatient department. Ultrasonic examination and CT were used to detect the residual stone and recurrence of renal cyst. RESULTS: The mean age of the patients was 45.3 ± 18.6 years. The average size of the parapelvic renal cysts was 4.3 ± 1.6 cm, including 27 with Bosniak category I and 1 patient with Bosniak II renal cysts. The mean size of the renal stones was 14.3 ± 3.9 mm. The mean operative time was 53.4 ± 20.7 minutes and the mean blood loss was 10.8 ± 5.6 ml. The mean hospitalization time was 3.2 ± 0.7 days. No severe complications were encountered. The complications included transient fever ( > 38°C) in 3 patients and significant hemorrhage in 1 patient. The stone-free rates one month and three months after operation were 89.3% and 96.4%, respectively. During the 2 years follow-up, the cyst recurrence rate was 14.3% and the stone recurrence rate was 7.1%. CONCLUSION: In this study, we firstly demonstrated that it is safe and effective to treat both renal stone and parapelvic renal cyst simultaneously by flexible ureteroscopic lithotripsy and flexible ureteroscopic incision and drainage, with satisfactory stone free rate and low cyst recurrence rate.

Adjustable single-incision mini-slings (Ajust®) versus other slings in surgical management of female stress urinary incontinence: a meta-analysis of effectiveness and complications.

BACKGROUND: Adjustable single-incision mini-sling (SIMS) is a new category of SIMS for stress urinary incontinence (SUI). The aim of this study was to compare the efficacy and safety of adjustable single-incision mini-sling with other slings. METHODS: Literature search in databases such as Pubmed, and Conchrane Library was performed up to December, 2015. The outcomes including cure rate, operation time, postoperative pain score and complications were reanalyzed. The pooled relative risk (RR) and mean difference (MD) with their 95% confidence interval (95% CI) were calculated by RevMan v5.0. RESULTS: Eight studies with 1093 SUI female patients were included. There was no significant difference between adjustable SIMS and other slings (transobturator slings and MiniArc) in patients subjective cure rate and objective cure rate. In addition, adjustable SIMS was associated with a significantly shorter operative time and lower postoperative pain score when comparing adjustable SIMS with transobturator tape (MD = - 1.35; 95%CI: -2.24 to - 0.46, P = 0.003). For the complications, there was also no significant difference between adjustable SIMS and transobturator slings. CONCLUSIONS: Adjustable SIMS had equally efficacy for SUI compared with transobturator slings and MiniArc. However, the significantly shorter operative time and lower postoperative pain score than transobturator tape supported the clinical application of adjustable SIMS.

MicroRNA expression profiles in benign prostatic hyperplasia.

Although alterations in microRNA (miRNA) expression have been previously investigated prostate cancer, the expression of miRNAs specifically in benign prostate hyperplasia (BPH) of the prostatic stroma remains to be fully elucidated. In the present study, miRNAs and gene expression profiles were investigated using microarray analysis and reverse transcription quantitative­polymerase chain reaction (RT­qPCR) in BPH tissue to clarify the associations between miRNA expression and target genes. Prostate tissue samples from five patients with BPH and five healthy men were analyzed using human Affymetrix miRNA and mRNA microarrays and differentially expressed miRNAs were validated using RT­qPCR with 30 BPH and 5 healthy control samples. A total of 8 miRNAs, including miRNA (miR)­96­5p, miR­1271­5p, miR­21­3p, miR­96­5p, miR­181a­5p, miR­143­3p, miR­4428 and miR­106a­5p were upregulated and 8 miRNAs (miR­16­5p, miR­19b­5p, miR­940, miR­25, miR­486­3p, miR­30a­3p, let­7c and miR­191) were downregulated. Additionally, miR­96­5p was demonstrated to have an inhibitory effect on the mRNA expression levels of the following genes: Mechanistic target of rapamycin (MTOR), RPTOR independent companion of MTOR complex 2, syntaxin 10, autophagy­related protein 9A, zinc finger E­box binding homeobox 1, caspase 2 and protein kinase c ε. Additionally, 16 differentially expressed miRNAs were identified using RT­qPCR analysis. This preliminary study provides a solid basis for a further functional study to investigate the underlying regulatory mechanisms of BPH.

Effects of microRNA-135a on the epithelial-mesenchymal transition, migration and invasion of bladder cancer cells by targeting GSK3ß through the Wnt/ß-catenin signaling pathway.

This study investigated the effects of microRNA-135a (miR-135a) targeting of glycogen synthase kinase 3ß (GSK3ß) on the epithelial-mesenchymal transition (EMT), migration and invasion of bladder cancer (BC) cells by mediating the Wnt/ß-catenin signaling pathway. BC and adjacent normal tissues were collected from 165 BC patients. Western blotting and quantitative real-time PCR were used to detect the expression of GSK3ß, ß-catenin, cyclinD1, E-cadherin, vimentin and miR-135a in BC tissues and cells. Cells were assigned to blank, negative control (NC), miR-135a mimics, miR-135a inhibitors, small interfering RNA (siRNA)-GSK3ß or miR-135a inhibitors+siRNA-GSK3ß groups. miR-135a, ß-catenin, cyclinD1 and vimentin expression increased, while GSK3ß and E-cadherin expression decreased in BC tissues compared with adjacent normal tissues. Compared with the blank and NC groups, the expression of miR-135a, ß-catenin, cyclinD1 and vimentin was higher, and cell proliferation, migration, invasion and tumor growth were increased in the miR-135a mimics and siRNA-GSK3ß groups. These groups showed an opposite trend in GSK3ß and E-cadherin expression and cell apoptosis. The miR-135a inhibitors group was inversely correlated with the blank and NC groups. It was concluded that miR-135a accelerates the EMT, invasion and migration of BC cells by activating the Wnt/ß-catenin signaling pathway through the downregulation of GSK3ß expression.

Ureteral double J stent displaced into vena cava and management with laparoscopy: A case report and review of the literature.

We reported displacement of a ureteral double J stent into the vena cava and laparoscopic management in a 69-year-old patient with a history of ureteral stent placement. Preoperative computed tomography and plain X-rays showed malpositioning of the double J stent and displacement into the inferior vena cava. The characteristics of stent misplacement precluded endovascular procedures and explorative laparoscopic surgery was performed. The intra- and postoperative periods were uneventful. Postoperative imaging demonstrated that the new double J stent was in the right position. The patient was discharged 7 d after the operation and was symptom free at the 4-mo follow-up.

CUL4B promotes bladder cancer metastasis and induces epithelial-to-mesenchymal transition by activating the Wnt/ß-catenin signaling pathway.

Increased expression of cullin 4B (CUL4B) is linked to progression in several cancers. This study aims to explore the effects of CUL4B on bladder cancer (BC) metastasis and epithelial-to-mesenchymal transition (EMT) and potential correlation to the Wnt/ß-catenin signaling pathway. We collected BC tissues and adjacent normal tissues from 124 BC patients. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were employed in order to detect the expression of Wnt/ß-catenin signaling pathway-related proteins and EMT markers. MTT and Transwell assays were used in order to measure cell proliferation, migration, and invasion. BC 5637 cells were transfected with control, siRNA scramble control (siRNA-NC), si-CUL4B, and CUL4B or Wnt inhibitory factor 1 (WIF-1) overexpression constructs. Levels of CUL4B mRNA and protein were increased in BC tissues in comparison with the adjacent normal tissues. CUL4B expression was negatively correlated with the expression of E-cadherin and positively correlated to the expression of N-cadherin and Vimentin. Compared to the control group, levels of ß-catenin, cyclinD1, c-myc, MMP7, and EMT markers were reduced, whereas phosphorylated GSK3ßSer9 and E-cadherin levels were increased in the si-CUL4B and WIF-1 groups. In addition, cell proliferation, migration, and invasion abilities were also increased. Increasing CUL4B expression had the opposite effect. These findings suggest that CUL4B induces EMT and promotes metastasis of BC by activating the Wnt/ß-catenin signaling pathway.

Thymol inhibits bladder cancer cell proliferation via inducing cell cycle arrest and apoptosis.

Thymol is a phenolic compound with various pharmacological activities such as anti-inflammatory, anti-bacterial and anti-tumor effects. However, the effect of thymol on bladder cancer cell growth is still elusive. The purpose of this study is to investigate the efficacy of thymol in bladder cancer cells and its underlying mechanism. Thymol inhibited bladder cancer cell proliferation in a dose and time-dependent manner. We also observed cell cycle arrest at the G2/M phase after the treatment of thymol. Moreover, thymol could induce apoptosis in bladder cancer cells via the intrinsic pathway along with caspase-3/9 activation, release of cytochrome c and down-regulation of anti-apoptotic Bcl-2 family proteins. The activation of JNK and p38 was also critical for thymol-induced apoptosis since it was abrogated by the treatment of JNK inhibitor (SP600125), and p38 inhibitor (SB203580) but not ERK inhibitor (SCH772984). Furthermore, the generation of ROS (reactive oxygen species) was detected after the treatment of thymol. ROS scavenger NAC (N-acetyl cysteine) could block the thymol-triggered apoptosis and activation of MAPKs. These findings offer a novel therapeutic approach for bladder cancer.

Ureteroscopic management of asymptomatic and symptomatic simple parapelvic renal cysts.

BACKGROUND: To investigate feasibility and safety of treating simple parapelvic renal cysts using flexible ureteroscopy with the Holmium laser. METHODS: Between February 2010 and July 2013, a total of 21 patients, aging from 29 to 71 (49.00 ± 13.23), were diagnosed with parapelvic renal cysts by ultrasonography in combination with contrast-enhanced computer tomography (CT) and intravenous urography (IVU) in the Department of Urology Surgery, People's Hospital of the Zhejiang province. Fifteen patients were asymptomatic and 6 patients were symptomatic with flank pain. All patients underwent drainage of the cysts using flexible ureteroscopy with Holmium laser. Patients were followed up 1, 3 and 12 months after the operation. RESULTS: The intervention was successful in 20 patients and failed in 1 patient who, subsequently successfully underwent a laparoscopic cyst removal. There were no intra-operative and post-operative complications reported. The mean operation time was 27 min (range: 15 to 45 min). The mean hospital stay was 2.6 days (range: 1 to 5 days). Twenty patients were followed up until 15 months after surgery. After such ureteroscopic management, there were no renal cysts detected in 7 patients (35 %) and a reduction in size of the renal cysts was found in 13 patients (65 %). Flank pain subsided in all 6 (100 %) previously symptomatic patients. CONCLUSIONS: Flexible ureteroscopy with the Holmium laser may be a feasible and effective treatment option in selected patients with simple parapelvic renal cysts. Further prospective randomized studies that compare the procedure to laparoscopic treatments are needed.

Marked improvement of anti-N-methyl-D-aspartate receptor encephalitis by large-dose methylprednisolone and plasmapheresis therapy combined with 18F-fluorodeoxyglucose positron emission tomography imaging: A case report.

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, a recently defined and frequently misdiagnosed disease characterized by psychiatric symptoms, seizures, movement disorders and autonomic dysfunction, has been observed predominantly in young females with ovarian teratoma. Conventional imaging techniques, including computed tomography (CT) and magnetic resonance imaging (MRI), are often ineffective for diagnosis of the disease. If diagnosed early, the initiation of immunotherapy and removal of the tumor (if present) may result in recovery. The current study presents the case of a 38-year-old female with classic clinical symptoms of anti-NMDAR encephalitis. The MRI brain scan results were unremarkable, cerebral spinal fluid (CSF) biochemistry indicated non-specific lymphocytic pleocytosis and the CSF microbiology studies were negative. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) imaging revealed significant generalized asymmetric hypometabolism. The patient demonstrated marked recovery following treatment with a high dose of corticosteroids and plasmapheresis. Accordingly, the follow-up 18F-FDG PET imaging revealed significant improvement.

[Transperineal laparoscopic nephrectomy in live-donors].

OBJECTIVE: To evaluate the feasibility and safety of transperitoneal laparoscopic nephrectomy in live-donors. METHODS: Two cases of live-donor underwent laparoscopic nephrectomy in May and August 2008 respectively and both were followed up. RESULT: In two cases the operation time was 130, 10 min; blood loss was 50 ml; warm ischemic time was 30 s and 2 min; the length of artery was 4.0 cm and 3.5 cm; the length of vein was 3.0 cm. The grafted kidneys started to produce urine at 30 s and 10 s after blood supply. Renal function of donor returned to normal after two days. The donors were discharged at 7th day after the operation. Renal function of recipient was normal after 3 days. CONCLUSION: Transperitoneal laparoscopic nephrectomy in live-donor is a safe and effective procedure, which provides kidney with satisfactory blood vessels and ureter for graft.

[Detection of transfusion transmitted virus infection of healthy blood donors in Hangzhou region and nucleotide sequence analysis of partial positive samples]

OBJECTIVE: To investigate the frequency of transfusion transmitted virus (TTV) infection in healthy blood donors in Hangzhou area and the mutation of TTV genomic fragment. METHODS DNA in serum samples of 203 healthy donors was extracted by phenol-chloroform method to detect TTV by semi-nested polymerase chain reaction and nucleotide sequences of partial amplification products were determined after T-A cloning. RESULTS TTV infection rate in 203 cases of blood donors in Hangzhou area was 15.3%. The homology of the amplified products of partial TTV positive samples compared with thereported nucleotide and putative amino acid sequences of TTV TA278 were 63.51% approximate, equals 67.12% and 59.46% approximate, equals 66.22% respectively. CONCLUSIONS TTV infection rate in the blood donors in Hangzhou is relatively high. The TTV infecting blood donors in the area may be a kind of novel genotype.