Detrusor underactivity influences the efficacy of TURP in patients with BPO.

PURPOSE: To investigate the effect of detrusor underactivity on the efficacy of TURP in patients with benign prostate obstruction. METHODS: A retrospective study of 350 patients with benign prostate obstruction who underwent TURP was carried out. Different degrees of bladder outlet obstruction were grouped by the bladder outlet obstruction index. ROC curves were used to calculate the optimal cut-off point for the bladder contractility index used to divide the DU patients into mild DU and severe DU patients. The effect of DU on the efficacy of TURP in benign prostate obstruction patients was studied by comparing the subjective and objective parameters preoperatively and 3 months postoperatively between severe DU, mild DU and non-DU benign prostate obstruction patients in two obstruction groups (20 ≤ BOOI < 40 and BOOI ≥ 40). RESULTS: According to the ROC curve, the optimal cut-off point for the bladder contractility index was 82; thus, 69 patients were considered mild DU patients (82 ≤ BCI < 100), 67 patients were considered severe DU patients (BCI < 82), and 214 patients were considered non-DU patients (BCI ≥ 100). Both the postoperative subjective and objective parameters of the non-DU, mild DU and severe DU patients significantly improved in two obstruction groups. However, in the 20 ≤ BOOI < 40 group, the successful improvement rates for the IPSS, IPSS-S, IPSS-V, QoL and fQmax in the severe DU patients were only 38.2%, 38.2%, 44.1%, 41.2% and 38.2%, respectively. CONCLUSION: Patients with varying degrees of benign prostate obstruction can benefit from TURP, but for patients with severe DU in the 20 ≤ BOOI < 40 group, TURP should be considered only after deliberation.

Comparison of Two Numerical Parameters to Assess Detrusor Contractility in Prognosing Short-Term Outcome after Transurethral Resection of the Prostate.

OBJECTIVE: To investigate and compare the influence of two numerical detrusor contractility parameters, the bladder contractility index (BCI) and the maximum Watts factor (WFmax), on transurethral resection of the prostate (TURP) outcome. METHODS: A retrospective study was conducted on 236 patients who had undergone urodynamic assessment preoperatively and TURP for benign prostatic obstruction. They were evaluated by International Prostate Symptom Score (IPSS) and uroflowmetry preoperatively and 3 months postoperatively. Related criteria were established to determine the overall efficacy of TURP. Logistic regression analysis and receiver operating characteristic curves were made to investigate the influence of the BCI and WFmax on TURP efficacy. RESULTS: Among the 236 patients, 195 treatments were effective and 41 ineffective. Multivariate analysis showed that both the BCI (OR 1.038) and the WFmax (OR 1.291) could influence TURP efficacy. For predicting TURP efficacy, the optimal cut-off values of the BCI and WFmax were 98.7 and 10.27 W/m2, respectively. The AUC, sensitivity and specificity of the BCI were 0.722, 78.5% and 61.0%; those of the WFmax were 0.761, 73.9% and 73.2%, with no significant difference (p > 0.05). CONCLUSIONS: To some extent, the BCI and the WFmax can predict TURP efficacy equally well. A discrimination level of 10.27 W/m2 may be a threshold value for detrusor underactivity (DU); as regards the BCI, the current threshold value is appropriate to diagnose DU.

Non-functional paraganglioma of urinary bladder managed by transurethral resection

ABSTRACT Purpose As a rare bladder tumor, paraganglioma of the urinary bladder (PUB) is frequently misdiagnosed as bladder cancer, particularly for the non-functional type. To date, transurethral resection remains a controversial treatment for non-functional PUB. This study aimed to identify the clinical features, pathological characteristics, prognosis, and safe/effective treatment of non-functional PUB using transurethral resection of the bladder tumor (TURBT). Materials and Methods The clinical records, radiological data, pathological characteristics and follow-up times were retrospectively reviewed in 10 patients with clinically and pathologically proven non-functional PUB in our hospital from January 2008 to November 2016. All patients underwent TURBT treatment. Results The incidence of non-functional PUB in patients with bladder cancer was 0.17%. The mean age at diagnosis was 44.5 ± 13.6 years (range, 29-70 years), and the patient population had a female: male ratio of 3: 2. No patients had excess catecholamine (CA) whilst four patients had painless hematuria. All neoplasms were completely resected via TURBT. The majority of samples were positive for immunohistochemical markers including chromogranin A (CgA) and Synaptophysin (Syn), but were negative for cytokeratins (CKs). Only a single recurrence was observed from the mean follow-up period of 36.4 ± 24.8 months. Conclusion Complete TURBT is a safe and efficient treatment that serves both diagnostic and therapeutic purposes. Histopathological and immunohistochemistry examinations are mandatory for diagnostic confirmation. Long-term follow-up is recommended for patients with non-functional PUB.

Non-functional paraganglioma of urinary bladder managed by transurethral resection.

PURPOSE: As a rare bladder tumor, paraganglioma of the urinary bladder (PUB) is frequently misdiagnosed as bladder cancer, particularly for the non-functional type. To date, transurethral resection remains a controversial treatment for non-functional PUB. This study aimed to identify the clinical features, pathological characteristics, prognosis, and safe/effective treatment of non-functional PUB using transurethral resection of the bladder tumor (TURBT). MATERIALS AND METHODS: The clinical records, radiological data, pathological characteristics and follow-up times were retrospectively reviewed in 10 patients with clinically and pathologically proven non-functional PUB in our hospital from January 2008 to November 2016. All patients underwent TURBT treatment. RESULTS: The incidence of non-functional PUB in patients with bladder cancer was 0.17%. The mean age at diagnosis was 44.5 ± 13.6 years (range, 29-70 years), and the patient population had a female: male ratio of 3: 2. No patients had excess catecholamine (CA) whilst four patients had painless hematuria. All neoplasms were completely resected via TURBT. The majority of samples were positive for immunohistochemical markers including chromogranin A (CgA) and Synaptophysin (Syn), but were negative for cytokeratins (CKs). Only a single recurrence was observed from the mean follow-up period of 36.4 ± 24.8 months. CONCLUSION: Complete TURBT is a safe and effi cient treatment that serves both diagnostic and therapeutic purposes. Histopathological and immunohistochemistry examinations are mandatory for diagnostic confi rmation. Long-term follow-up is recommended for patients with non-functional PUB.

RPS7 promotes cell migration through targeting epithelial-mesenchymal transition in prostate cancer.

OBJECTIVES: Small ribosomal protein subunit 7 (RPS7) is an important structural components of the ribosome involved in protein synthesis, previous studies demonstrated that RPS7 was associated with several malignancies, but the role of RPS7 in prostate cancer (PCa) remains unclear. To decipher such a puzzle, in the current study, we deciphered the role and mechanism of RPS7 during the progression of PCa. MATERIAL AND METHODS: In this study, the expression of mRNA was performed by quantitative real-time PCR. The protein level was identified by Western blotting. Kaplan-Meier survival analysis was demonstrated the relation between the abnormal expression of RPS7 mRNA and the overall survival. Cell proliferation was assessed by MTT assay and cell counting, meanwhile, cell migration was checked by transwell assay. RESULTS: RPS7 is higher expressed in PCa (p < 0.001), and the overexpression of RPS7 is closely associated with poor outcome of PCa patients after radical prostatectomy (p < 0.001). Inhibition the expression of RPS7 with a specific RPS7 siRNA could markedly attenuate prostate tumor growth and migration (p < 0.05). Mechanistic data reveals that inhibition of RPS7 could up-regulate the epithelial protein marker, E-cadherin (p < 0.05), and down-regulate the mesenchymal protein markers, such as N-cadherin and Snail (p < 0.001). CONCLUSIONS: RPS7 is a newly verified tumor promoter in PCa, and promotes cell migration by targeting epithelial-to-mesenchymal transitionpathway. Thus, inhibition of RPS7-epithelial to-mesenchymal transition signaling might represent a prospective approach toward limiting prostate tumor progression.

PSMA5 promotes the tumorigenic process of prostate cancer and is related to bortezomib resistance.

Proteasome α5 subunit (PSMA5) is related to poor prognosis in various cancers. The first therapeutic proteasome inhibitor, bortezomib, induces apoptosis, suppressing cell growth in many tumor types. However, the effects of PSMA5 and bortezomib in prostate cancer (PCa) are still unknown. In this study, we investigated whether PSMA5 is associated with the tumorigenic progression and the interaction of PSMA5 with bortezomib in PCa. We knocked down PSMA5 with siRNA and studied the changes in cell viability and motility with Cell Counting Kit-8, quantitative PCR, fluorescence-activated cell sorting, scratch, and invasion assays. We also investigated the effect of PSMA5 in PCa cells treated with bortezomib and in those that are resistant to bortezomib. We found that silencing PSMA5 inhibited cell proliferation, induced apoptosis, restricted cell migration and invasion, and demonstrated a coordinated effect with bortezomib. Cells resistant to bortezomib gained sensitivity to bortezomib after PSMA5 was knocked down. Our results show, for the first time, that PSMA5 promotes the tumorigenic process of PCa and is linked to bortezomib resistance.

Kinase PIM1 promotes prostate cancer cell growth via c-Myc-RPS7-driven ribosomal stress.

Ribosomal stress is known to increase cancer risk; however, the molecular mechanism underlying its various effects on cancer remains unclear. To decipher this puzzle, we investigated the upstream signaling pathway that might be involved in promoting ribosomal stress that leads to tumor progression. Our results suggested that inhibition of kinase PIM1 attenuated PC3 cell growth and motility following the condensed cellular body and decreased protein translation in PIM1-inhibited cells. In addition, PIM1 was found to be a component of the small 40S ribosomal subunit and could regulate the expression of ribosomal small subunit protein 7 (RPS7). Our investigation also revealed that PIM1 enhanced the protein stability of c-Myc. Furthermore, a functional E-box motif was found upstream of the transcription start site in RPS7, and RPS7 has been proven to be a transcriptional target of c-Myc. Additionally, knocking down RPS7 dramatically reduced cell growth in vitro and in vivo, whereas enhancing RPS7 expression reversed the condensed cellular body and decreased protein translation resulted from PIM1 inhibition. Finally, biochemical recurrence-free survival and overall survival analysis indicated that the concomitant upregulation of PIM1 and RPS7 correlated with the worst prognosis of prostate cancer (PCa). Overall, our results demonstrated that kinase PIM1 promotes cell growth through c-Myc-RPS7-induced ribosomal stress in PCa. These findings substantially expanded our understanding on the molecular mechanism of PIM1-promoted abnormal ribosomal biosynthesis in tumorigenesis and tumor progression in PCa. Therapies that target molecules involved in PIM1-RPS7-induced ribosomal stress could provide a promising approach to treating PCa.

Antimony enhances c-Myc stability in prostate cancer via activating CtBP2-ROCK1 signaling pathway.

Antimony, one of the heavier pnictogens, is widely used in industry, and its toxicity has become a major concern. Although previous studies suggested that antimony might be a tumorigenic risk factor in several cancers, the molecular basis underlying antimony-mediated transformation remains unclear. Our results showed that the serum concentration of antimony was higher in prostate cancer specimens relative to that of benign prostate tissues, and this high serum concentration of antimony was closely associated with poorer outcome in prostate cancer patients. Additionally, we demonstrated that antimony could promote prostate cancer cell growth in vitro and in vivo. In order to gain insight into the potential mechanisms, we examined the effects of antimony exposure on downstream signaling that could contribute to tumor development. We found that low-dose antimony could regulate the expression of Ctbp2 by binding and regulating the activity of its MRE domain. Meanwhile, CtBP2 could transcriptionally regulate the expression of RhoC, which is a member of the RhoGTPase family. Subsequently, the kinase activity of ROCK1 is increased, which promotes the stability of oncogene c-Myc. Overall, our study demonstrated that antimony could enhance c-Myc protein stability and promote prostate cancer cell proliferation through activating CtBP2-ROCK1 signaling pathway. These findings also substantially highlighted the potential of targeting molecules within antimony induced CtBP2-c-Myc signaling pathway as a promising therapeutic approach for the treatment of prostate cancer.

Elevated expression of ZNF217 promotes prostate cancer growth by restraining ferroportin-conducted iron egress.

Although we and other studies indicated ZNF217 expression was increased in prostate cancer (PCa), the factors mediating its misregulated expression and their oncogenic activity remain largely unexplored. Recent evidence demonstrated that ferroportin (FPN) reduction lead to decreased iron export and increased intercellular iron that consequently aggravates the oncogenic effects of iron. In the present study, ZNF217 was identified as a transcriptional repressor that inhibits FPN expression. Increased of ZNF217 expression led to decreased FPN concentration, coupled with resultant intracellular iron retention, increased iron-related cellular activities and enhanced tumor cell growth. In contrast, decreased of ZNF217 expression restrained tumor cell growth by promoting FPN-driven iron egress. Mechanistic investigation manifested that ZNF217 facilitated the H3K27me3 levels of FPN promoter by interacting with EZH2. Besides, we also found that MAZ increased the transcription level of ZNF217, and subsequently inhibited the FPN expression and their iron-related activities. Strikingly, the expression of MAZ, EZH2 and ZNF217 were concurrently upregulated in PCa, leading to decreased expression of FPN, which induce disordered iron metabolism. Collectively, this study underscored that elevated expression of ZNF217 promotes prostate cancer growth by restraining FPN-conducted iron egress.

miR-539 inhibits prostate cancer progression by directly targeting SPAG5.

BACKGROUND: We conducted multiple microarray datasets analyses from clinical and xenograft tumor tissues to search for disease progression-driving oncogenes in prostate cancer (PCa). Sperm-associated antigen 5 (SPAG5) attracted our attention. SPAG5 was recently identified as an oncogene participating in lung cancer and cervical cancer progression. However, the roles of SPAG5 in PCa progression remain unknown. METHODS: SPAG5 expression level in clinical primary PCa, metastatic PCa, castration resistant PCa, neuroendocrine PCa, and normal prostate tissues was investigated. We established multiple in vivo xenografts models using patient-derived tissues and investigated SPAG5 expression trend in these models. We also investigated the functions of SPAG5 in vivo and in vitro studies. Luciferase reporter assays were performed to investigate potential miRNAs that can regulate SPAG5. RESULTS: We identified that SPAG5 expression was gradually increased in PCa progression and its level was significantly associated with lymph node metastasis, clinical stage, Gleason score, and biochemical recurrence. Our results indicated that SPAG5 knockdown can drastically inhibit PCa cell proliferation, migration, and invasion in vitro and supress tumor growth and metastasis in vivo. We identified that miR-539 can directly target SPAG5. Ectopic overexpression of miR-539 can drastically inhibit SPAG5 expression and the restoration of SPAG5 expression can reverse the inhibitory effects of miR-539 on PCa cell proliferation and metastasis. CONCLUSION: Our results collectively showed a progression-driving role of SPAG5 in PCa which can be regulated by miR-539, suggesting that miR-539/SPAG5 can serve as a potential therapeutic target for PCa.

Prognostic significance of GPC5 expression in patients with prostate cancer.

The objective of this study was to evaluate the protein level of glypican-5 (GPC5) and its relationship with clinicopathologic significance in prostate cancer. The protein level of GPC5 in 160 prostate cancer tissues and 60 adjacent normal samples was examined by immunohistochemistry analysis, and the results were correlated with clinicopathologic parameters. The level of GPC5 in prostate cancer tissues was markedly lower than that in normal cases, especially in high-risk prostate cancer. Additionally, the low expression of GPC5 was closely associated with increased serum prostate-specific antigen (PSA), higher Gleason scores, advanced tumor stage (T3), positive lymph node metastasis, and biochemical recurrence. Moreover, GPC5 low expression was an independent prognostic factor for overall survival of patients with prostate cancer. GPC5 protein expression showed a close correlation with the tumorigenesis and tumor progression of prostate cancer, and that might be applied as a novel biomarker for the prediction of diagnosis and prognosis of prostate cancer.

CtBP2 overexpression is associated with tumorigenesis and poor clinical outcome of prostate cancer.

INTRODUCTION: The aim of the study was to evaluate the expression of CtBP2 in prostate cancer and to determine its relationship with clinicopathologic parameters. MATERIAL AND METHODS: The expression of CtBP2 in 119 prostate cancer tissues and 41 normal tissues was examined by qPCR and Western blot analysis, and the results were correlated with clinicopathologic parameters. RESULTS: CtBP2 expression in prostate cancer tissues was higher than that in normal samples. CtBP2 overexpression was closely correlated with serum prostatic specific antigen (PSA) (p = 0.018), advanced tumor stage (T3) (p = 0.025), higher Gleason scores (p = 0.019), positive extraprostatic extension (p = 0.012), positive vascular invasion (p = 0.011) and perineural invasion (p = 0.035). However, no significant association was found between CtBP2 abnormal expression and other parameters, including age (p = 0.776), positive lymph node (p = 0.872) and positive surgical margin (p = 0.37). Moreover, CtBP2 overexpression was significantly associated with poor clinical outcome of prostate cancer (p = 0.0168). CONCLUSIONS: CtBP2 is overexpressed in prostate cancer, and its increased expression is closely associated with tumor progression and the outcome of prostate cancer.

Impact of stone branch number on outcomes of percutaneous nephrolithotomy for treatment of staghorn calculi.

PURPOSE: To determine the impact of staghorn calculi branch number on outcomes of percutaneous nephrolithotomy (PNL). MATERIALS AND METHODS: Retrospectively, we evaluated 371 patients (386 renal units) who underwent PNL for staghorn calculi. All calculi were showed with CT three-dimensional reconstruction (3DR) imaging preoperatively. From 3DR images, the number of stone branching into minor renal calices was recorded. According to the number, patients were divided into four groups. Group 1: the branch number 2-4; Group 2: the branch number 5-7; Group 3: the branch number 8-10; Group 4: the branch number >10. The number of percutaneous tract, operative time, staged PNL, intraoperative blood loss, postoperative hospital stay, complications, main stone composition, and stone clearance rate were compared. RESULTS: A significantly higher ratio of multitract (p<0.001) and staged PNL (p<0.001), a longer operative time (p<0.001) and postoperative hospital stay (p=0.043), and a lower rate of stone clearance (p<0.05) were found in PNL for calculi with a stone branch number ≥5. There was no statistical difference in intraoperative blood loss (p=0.101) and main stone composition (p=0.546). There was no statistically meaningful difference among the four groups based on the Clavien complication system (p=0.46). CONCLUSION: With the stone branch number more than five, the possibility of multitract and staged PNL, lower rate of stone clearance, and a longer postoperative hospital stay increases for staghorn calculi.

New retractor facilitates exposure of the vascular pedicles in Chinese men with complex pelvis during radical cystectomy.

OBJECTIVE: To evaluate the surgical instrument, the double-slice retractor of pelvis (DBR), for the division of the vascular pedicles from the bladder and prostate in male patients with complex pelvis during radical cystectomy. METHODS: Radical cystectomy was performed on 140 male patients (all cases body mass index >28 kg/m(2), 29 cases having undergone partial cystectomy) with bladder cancer. With the aid of the double-slice retractor to expose vascular pedicles from the bladder and prostate, 80 radical cystectomies were performed. The others were treated as the control. RESULTS: The double-slice retractor provided excellent exposure for the division of vascular pedicles from the bladder and prostate. The handling of the vascular pedicles from the bladder and prostate became easier and safer without unnecessary bleeding and injury in the rectum. In double-slice retractor and control groups, the operative time to handle the vascular pedicles during radical cystectomy in the double-slice retractor group was 12.2 ± 1.4 min compared with 22.6 ± 3.4 min for the control group (P < 0.05), and the blood loss was 30.3 ± 2.2 ml compared with 50.2 ± 4.5 ml (P < 0.05). For the whole radical cystectomy procedure, the operative time lasted 72.1 ± 9.2 min in the double-slice retractor group compared with 85.7 ± 6.8 min for the control group (P < 0.05), the whole blood loss was reduced to 340.3 ± 12.7 ml from 410.1 ± 11.4 ml in the control group (P < 0.05). And the rate of transfusion was geared down to 10% in the double-slice retractor group from 25% in the control (P < 0.05). CONCLUSIONS: The use of the double-slice retractor for the exposure of vascular pedicles from the bladder and prostate is simple and effective in male patients with complex pelvis during radical cystectomy. We have devised a promising surgical instrument for the exposure of vascular pedicles.

Laparoscopic simple enucleation and coagulation on tumor bed using argon beam coagulator for treating small renal cell carcinomas: an animal study followed by clinical application.

MATERIAL/METHODS: The animal experiments of coagulation therapy on the wound tissue bed during partial nephrectomy with an argon beam coagulator were performed on 16 rabbits, which were randomly divided into 4 groups. Groups A and B had renal artery occlusion; the treatment time of coagulation was 4 seconds and 6 seconds, respectively. Groups C and D did not have renal artery occlusion; the treatment time of coagulation was 2 seconds and 4 seconds, respectively. Then 30 clinical operations of laparoscopic simple enucleation and coagulation on tumor bed using an argon beam coagulator were performed. RESULTS: All 16 rabbits successfully underwent the operation. By the histological examination, the scab depth of the wound tissue bed in groups A, B, C, and D were 2.76 ± 0.17 mm, 3.15 ± 0.15 mm, 2.28 ± 0.16 mm and 2.75 ± 0.06 mm, respectively. Group A differed significantly from groups B and C (P=0.012, 0.007), and group D differed significantly from groups B and C (P=0.002, 0.002). In the clinical study, all 30 patients successfully underwent the operation. The mean operative time was 182 minutes, and the mean blood loss was 280 ml. With a median follow-up time of 37 months, neither local recurrence nor distant metastasis was found by computerized tomography scan. CONCLUSIONS: Laparoscopic simple enucleation and coagulation on tumor bed using an argon beam coagulator can be considered for treating small renal cell carcinomas. However, the indication of this procedure should be highly selected.

[Overexpression of PTEN gene inhibits proliferation of bladder transitional carcinoma cell line EJ].

OBJECTIVE: To evaluate the anticancer effects of exogenous human WT-PTEN overexpression on bladder transitional carcinoma cell line EJ. METHODS: The plasmid containing WT-PTEN or mutant PTEN was separately transfected into bladder transitional carcinoma cell line EJ, and the protein expression of PTEN in the EJ cells was detected by Western blot. Cell morphological changes were observed under the inverted microscope and transmission electron microscope. MTT test was used to assess the effect of PTEN on proliferation and anticancer effects for mitomycin and theraubicin. The change of bcl-2 expression in the cells was measured by Western blot. The empty plasmid was used as control. RESULTS: Western blot analysis showed that EJ cells expressed high level of PTEN protein after transfection with WT-PTEN or mutant PTEN plasmid. Abnormal morphological changes of the cells were observed in WT-PTEN transfected groups. The growth of EJ cells treated with WT-PTEN was significantly inhibited by 40.1% and anticancer effects were enhanced by mitomycin and theraubicin, but the cells transfected with mutant PTEN plasmid did not show such similar biological behavior. CONCLUSION: WT-PTEN gene transfection can suppress the in vitro growth and induce apoptosis of bladder transitional carcinoma cell line EJ cells. Mutant PTEN does not show similar biological behavior. Overexpression of WT-PTEN inhibits cancer cell proliferation by down-regulating bcl-2 expression in the cells.