Yu-Peng Wu

Predictors of Recoverability of Renal Function after Pyeloplasty in Adults with Ureteropelvic Junction Obstruction

Background: This study aimed to identify factors predicting the recoverability of renal function after pyeloplasty in adult patients with ureteropelvic junction obstruction. Methods: We retrospectively reviewed 138 adults with unilateral renal obstruction-induced hydronephrosis and who underwent Anderson-Hynes dismembered pyeloplasty from January 2013 to January 2016. Hydronephrosis was classified preoperatively according to the Society for Fetal Urology (SFU) grading system. All patients underwent Doppler ultrasonography, excretory urography, computed tomography, and technetium-99m-diethylenetriamine pentaacetic acid radioisotope (99mTc DTPA) renography before and after surgery. Renal resistive index (RRI) and 99mTc DTPA renography were repeated at 1, 3, 6, and 12 months. Results: Multivariate analysis identified age, renal pelvic type, SFU grade, preoperative RRI, decline of RRI, and renal parenchyma to hydronephrosis area ratio (PHAR) as independent predictors of renal function recoverability after pyeloplasty. However, preoperative RRI and RRI decline were not significantly associated with recoverability of renal function in patients aged >35 years. Lower preoperative RRI, greater decline in RRI, higher PHAR, lower SFU grade, and extrarenal pelvis were associated with greater improvements in postoperative renal function. Conclusions: Preoperative differential renal function cannot independently predict the recoverability of postoperative renal function in adult patients with unilateral renal obstruction-induced hydronephrosis. SFU grade, renal pelvic type, PHAR, preoperative RRI, and decline in RRI were significantly associated with the recoverability of renal function in adult patients aged <35 years, while only SFU grade, renal pelvic type, and PHAR were significantly associated with renal function recoverability in patients aged ≥35 years. Renal function recovery was better in patients younger than 35 years when compared with older patients.

Risk factors for bladder cancer recurrence survival in patients with upper-tract urothelial carcinoma

Purpose: The aim of this work was to investigate the predictive factors for bladder cancer recurrence survival (BCRS) in patients with upper-tract urothelial carcinoma (UTUC). Methods: We selected patients with UTUC who underwent segmental ureterectomy (Su) or nephroureterectomy (Nu) from 2004 to 2013 from the Surveillance, Epidemiology, and End Results (SEER) database. Patients with a history of intravesical therapy for bladder cancer and bladder cancer prior to the diagnosis of UTUC were excluded. We used Kaplan-Meier analysis, log-rank tests, and Cox proportional hazards model to compare overall survival, cancer-specific survival, and BCRS. Results: In a cohort of 1,454 patients, 169 (11.6%) had low-grade tumors and 1,285 (88.4%) had high-grade tumors; 239 (16.4%) underwent Su and 1,215 (83.6%) underwent Nu. We found that T4 grade (hazard ratio [HR] = 6.216; 95% confidence interval [CI], 3.197-12.087) and ureteral tumors (HR = 1.764; 95% CI, 1.173-2.652) were predictors of shorter BCRS, whereas Nu (HR = 0.608; 95% CI, 0.388-0.953) predicted longer BCRS. Five-year BCRS rates were low-grade tumors: 94.1%, high-grade tumors: 85.4% (p = 0.038); plus Su: 82.9%, and Nu: 87.6% (p = 0.016). Conclusions: Use of Su should be more selective for high-grade tumors, as it correlates with shorter BCRS. Tumors located in the ureter are associated with shorter BCRS than those located in the renal pelvis.

Molecular network-based identification of competing endogenous RNAs and mRNA signatures that predict survival in prostate cancer

BackgroundThe aim of the study is described the regulatory mechanisms and prognostic values of differentially expressed RNAs in prostate cancer and construct an mRNA signature that predicts survival.MethodsThe RNA profiles of 499 prostate cancer tissues and 52 non-prostate cancer tissues from TCGA were analyzed. The differential expression of RNAs was examined using the edgeR package. Survival was analyzed by Kaplan–Meier method. microRNA (miRNA), messenger RNA (mRNA), and long non-coding RNA (lncRNA) networks from the miRcode database were constructed, based on the differentially expressed RNAs between non-prostate and prostate cancer tissues.ResultsA total of 773 lncRNAs, 1417 mRNAs, and 58 miRNAs were differentially expressed between non-prostate and prostate cancer samples. The newly constructed ceRNA network comprised 63 prostate cancer-specific lncRNAs, 13 miRNAs, and 18 mRNAs. Three of 63 differentially expressed lncRNAs and 1 of 18 differentially expressed mRNAs were significantly associated with overall survival in prostate cancer (P value < 0.05). After the univariate and multivariate Cox regression analyses, 4 mRNAs (HOXB5, GPC2, PGA5, and AMBN) were screened and used to establish a predictive model for the overall survival of patients. Our ROC curve analysis revealed that the 4-mRNA signature performed well.ConclusionThese ceRNAs may play a critical role in the progression and metastasis of prostate cancer and are thus candidate therapeutic targets and potential prognostic biomarkers. A novel model that incorporated these candidates was established and might provide more powerful prognostic information in predicting survival in prostate cancer.

Increased Paxillin expression in prostate cancer is associated with advanced pathological features, lymph node metastases and biochemical recurrence

Purpose Paxillin regulates cell-cell adhesion, and altered Paxillin expression has been associated with human carcinogenesis. This study analyzed the association between Paxillin expression in prostate cancer (PCa) tissues with clinicopathological features, lymph node metastasis and biochemical PCa recurrence. Methods A total of 386 tissue specimens from PCa patients who received radical prostatectomy and 60 tissue specimens from benign prostatic hyperplasia (BPH) cases were collected to construct tissue microarrays, which were subsequently immunostained for Paxillin expression. Thirty positive lymph node tissue specimens and 10 healthy prostate tissue specimens were randomly selected for Paxillin immunostaining. Results The association between Paxillin expression, lymph node metastasis and biochemical PCa recurrence was analyzed. Paxillin expression was significantly higher in PCa than both normal and BPH tissues (P<0.001) and was correlated with preoperative prostate-specific antigen level, Gleason score, clinical tumor stage, lymph node metastasis, positive surgical margin, extracapsular extension and seminal vesicle invasion (P<0.05 for all). Logistic regression analysis showed that Paxillin and Gleason score were independent risk factors for PCa lymph node metastasis (P<0.05). The receiver operating characteristic (ROC) curve indicated that Paxillin expression (AUC=0.723) more accurately predicted PCa lymph node metastasis than Gleason score (AUC=0.692). Kaplan-Meier curve analysis showed that increased Paxillin expression was associated with shortened biochemical-free survival (BFS) after radical prostatectomy (P<0.001). Conclusion Paxillin was significantly upregulated in PCa compared with BPH and normal tissues and associated with lymph node metastasis and shortened BFS of PCa. Further study will investigate the underlying molecular mechanism and the role of Paxillin in PCa.

Risk of upgrading from prostate biopsy to radical prostatectomy pathology: Is magnetic resonance imaging-guided biopsy more accurate?

Background: This study compared magnetic resonance imaging-guided biopsy (MRI-GB) and transrectal ultrasound guided biopsy (TRUS-GB) with the final histology of the radical prostatectomy (RP) specimen. Methods: Our subjects were 229 patients with prostate cancer (PCa), proven histopathologically using MRI-GB or TRUS-GB, who underwent RP at our center between December 2015 and December 2016. The main group included 92 patients who underwent MRI-GB and the control group included 137 patients who underwent 12-core TRUS-GB. Histological findings for RP specimens were compared with those from biopsies. We also evaluated predictors of upgraded Gleason score (GS), using uni- and multivariate analyses. Results: Upgraded GS between biopsy and RP specimen occurred to 22.7% (52/229) of the cohort overall. In univariate analysis, prostate-specific antigen density (PSAD) (P<0.001), prostate volume (PV) < 30 ml (P<0.001), biopsy modality (P=0.027), biopsy GS (P=0.032) and measured MRI lymph node metastasis (P=0.018) were prognostic factors. Multivariate logistic regression analysis showed PV < 30 ml (P<0.001) and biopsy modality (P=0.001) were independent predictors of upgraded GS. Conclusions: MRI-GB may enhance the diagnostic accuracy of prostate cancer detection in final histopathology with lower rate of upgraded GS than TRUS-GB. Also, PV < 30 ml and biopsy modality were independent predictors of upgraded GS.

Risk factors for infectious complications following transrectal ultrasound-guided prostate biopsy

Objective To explore risk factors of infectious complications following transrectal ultrasound-guided prostate biopsy (TRUSPB). Methods We retrospectively analyzed 1,203 patients with suspected prostate cancer who underwent TRUSPB at our center between December 2012 and December 2016. Demographics, clinical characteristics, and data regarding complications were collected, and then univariate and multivariate logistic regression analyses were used to identify independent risk factors for infectious complications after prostate biopsy. Results Multivariate logistic analysis demonstrated that body mass index (BMI) (OR=2.339, 95% CI 2.029–2.697, P<0.001), history of diabetes (OR=2.203, 95% CI 1.090–4.455, P=0.028), and preoperative catheterization (OR=2.303, 95% CI 1.119–4.737, P=0.023) were risk factors for infection after prostate biopsy. The area under the receiver operating characteristics curve for infectious complications was 0.930 (95% CI 0.907–0.953, P<0.001). BMI=28.196 kg/m2 was the best cut-off threshold for predicting infection after TRUSPB. Conclusion BMI >28.196 kg/m2, history of diabetes, and preoperative catheterization are independent risk factors for infection after prostate biopsy.

Fasudil inhibits actin polymerization and collagen synthesis and induces apoptosis in human urethral scar fibroblasts via the Rho/ROCK pathway

Purpose To examine the effects and mechanism of action of fasudil on cytoskeletal polymerization, collagen synthesis, and apoptosis in fibroblasts derived from human urethral scar tissue. Materials and methods Fibroblasts treated with or without transforming growth factor β1 (TGF-β1, 10 ng/mL) were incubated with fasudil (12.5, 25, 50 μmol/L) for 24 hours. Quantitative real-time polymerase chain reaction and Western blotting were used to determine the expression of Arp2, Arp3, WASP, and WAVE2. Collagen I and III protein levels were also evaluated by Western blotting. The filamentous actin cytoskeleton was examined by immunofluorescence and epifluorescence microscopy. An Annexin V-FITC/PI staining assay was used to investigate apoptosis. Results TGF-β1-dependent induction of actin polymerization and collagen synthesis and promotion of apoptosis were dose dependent. When compared with untreated controls, fasudil significantly decreased the expression of Arp2, Arp3, WASP, WAVE2, Collagen I, and Collagen III in cells treated with or without TGF-β1. Fasudil also promoted apoptosis in cells, irrespective of TGF-β1 treatment. Conclusion Irrespective of TGF-β1 activation status, fasudil suppressed actin polymerization and collagen synthesis and induced apoptosis in human urethral scar fibroblasts via the Rho/ROCK signaling pathway.

Upregulation of Arp2 expression is associated with the prognosis and prediction of lymph node metastasis in bladder urothelial carcinoma

Objective Upregulation of actin-related protein 2/3 complex subunit 2 (Arp2) is observed in various tumors, but its expression pattern has not been revealed in bladder urothelial carcinoma (BUC). The purpose of this study was to investigate the role of Arp2 expression in the pathological features and the prognosis as well as lymph node metastasis of BUC. Methods A total of 228 tissue specimens from BUC patients who underwent a radical cystectomy were collected. In addition, 40 lymph node specimens and 40 normal bladder tissue specimens as controls were used. All of the specimens were used to construct a tissue microarray and were subsequently subjected to immunohistochemical staining for Arp2 expression. Logistic and Cox regression analyses and Kaplan–Meier curve analysis were applied to analyze the relation between Arp2 expression and multiple clinical features of patients with BUC. Results Immunohistochemical staining observation showed that Arp2 was mainly expressed in the cytoplasm and nucleus of positive cells and that Arp2 expression in BUC was significantly higher than that in normal bladder tissues. Arp2 expression in BUC tissues was associated with tumor size, tumor multiplicity, tumor stage, tumor grade, and lymph node metastasis (P < 0.05). Logistic regression analysis demonstrated that Arp2 expression was an independent risk factor for lymph node metastasis of BUC (P < 0.05). Kaplan–Meier curve analysis showed that increased Arp2 expression was associated with a shortened recurrence-free survival (RFS) and overall survival (OS) of BUC patients after radical cystectomy (P < 0.05). Conclusion These findings suggest that Arp2 is significantly upregulated in BUC tissues when compared with normal bladder tissues, and that Arp2 expression is an independent predictor for lymph node metastasis, RFS, and OS.

Risk factors for upper tract urothelial recurrence following local excision of bladder cancer

The mechanism of upper tract recurrence after local excision of bladder cancer remains unknown. This study was designed to identify risk factors for upper tract urothelial recurrence following local tumor excision of bladder cancer. To identify 76 597 bladder cancer patients, comprising 76 537 nonrecurrence and 60 recurrence patients, the Surveillance, Epidemiology, and End Results database was used. Kaplan‐Meier analysis and univariate and multivariate Cox proportional hazards regression models were used to determine the risk factors. Compared with the nonrecurrence group, the recurrence group was associated with older age, higher grade, high T stage, and higher proportional squamous cell carcinomas. Univariate Cox proportional hazards regression model showed that age, grades III and IV, T stage, and pathology were significantly associated with worse upper tract urothelial recurrence (UTUR) survival. However, after adjusting for prognostic factors, grade was no longer an independent prognostic factor in multivariate analysis. This study demonstrates that clinical prognosis of UTUR after local bladder tumor excision has significant independent risk factors that include age ≥60 years, T1 and T2 stage, and squamous cell carcinoma, and will require more careful consideration during follow‐up.

Impact of Obesity on Long-Term Urinary Incontinence after Radical Prostatectomy: A Meta-Analysis

Obesity is a known risk factor for prostate cancer progression and may contribute to poor treatment outcomes. However, little is known concerning the relationship between obesity (body mass index [BMI] ⩾ 30) and the urinary incontinence (UI) of patients after radical prostatectomy (RP). The goal of this study was to focus on the prevalence and duration of UI after RP with specific attention to the BMI. Subsequently, trials were identified in a literature search of PubMed, Embase, Cochrane Library, Web of Science, and Google Scholar using appropriate search terms. All comparative studies reporting BMI, study characteristics, and outcome data including the relationship between BMI and urinary incontinence data were included. Finally, four studies comprising 6 trials with 2890 participants were included. The results showed that obesity increased UI risk at 12 months in patients who underwent robotic-assisted laparoscopic radical prostatectomy (RLRP) (odds ratio [OR] 2.43, 95% confidence interval [CI] [1.21, 4.88], P = 0.01). When stratified by the surgical methods, the pooled results showed that obesity increased UI risk at 24 months in patients who underwent RLRP (OR 2.00, 95% CI [1.57, 2.56], P < 0.001). However, in patients who underwent laparoscopic radical prostatectomy (LRP), the pooled results showed that obesity does not increase UI risk at 24 months (OR 1.13, 95% CI [0.74, 1.72], P = 0.58). This is the first study to include obesity as the primary independent variable. Outcomes indicate that obesity (BMI ≥ 30) may increase the UI risk at 12 and 24 months after RLRP. Well-designed randomized controlled trials with strict control of confounders are needed to make results comparable.