Possible predictor of early recovery on urinary continence after laparoscopic radical prostatectomy - Bladder neck level and urodynamic parameters.

BACKGROUND/PURPOSE: To investigate the relationship between post-operative bladder neck levels and urodynamic parameters and their effect on urinary incontinence after laparoscopic radical prostatectomy (LRP). METHODS: Forty-eight consecutive patients undergoing LRP were retrospectively reviewed. All patients were assessed using retrograde cystography after LRP and were grouped according to their bladder neck position: Level 0: at or above the superior margin of the symphysis pubis (SMSP); Level -1: at <2 cm below SMSP; and Level -2: at >2 cm below SMSP. Urodynamic studies were conducted at baseline as well as at 1 and 3 months post-operatively. Early recovery of urinary continence was defined as no urine leakage or only one pad/day used within 3 months after surgery. Demographic characteristics, changes in urodynamic parameters, and continence outcomes were analyzed. RESULTS: Overall rate of early recovery of urinary continence was 33.3%. Patients with higher bladder neck levels experienced a significantly earlier recovery of urinary continence in univariate analysis (77.8%, 29.2%, and 13.3% for bladder neck levels 0, -1, and -2, respectively, p = 0.004). Patients with early recovery of urinary continence had significantly longer functional profile lengths (FPLs) 1 month post-surgery (21.0 mm vs 14.8 mm, p = 0.019). Higher bladder neck levels were significantly associated with longer FPLs at 1 month (p = 0.032). CONCLUSION: Bladder neck level is associated with FPLs at 1 month post-surgery, which is the possible predictor of early recovery of urinary continence after LRP. Patients with longer FPL at 1 month after LRP have a higher rate of early recovery of urine continence.

Factors affecting operative efficiency and post-operative convalescence in laparoendoscopic single-site (LESS) adrenalectomy.

BACKGROUND: Laparoendoscopic single-site (LESS) adrenalectomy is a novel challenging technique which is still under clinical evaluation. Initial reports have revealed its superiority in patient convalescence. In addition, it has been reported that some patient or anatomic factors might affect the ergonomics of LESS adrenalectomy. The aim of this study is to investigate the possible factors that might affect procedural efficiency and patient convalescence in LESS adrenalectomy. METHODS: Between October 2009 and July 2015, 105 consecutive adult patients with benign adrenal tumors, who underwent LESS retroperitoneal adrenalectomy were enrolled in this study. All the relevant peri-operative parameters were prospectively collected for later analysis. By using stepwise linear regression and stepwise selection of these peri-operative parameters, those that might affect the operative efficiency and patient convalescence were analyzed. RESULTS: Finally, 78 patients who completed follow-up and were eligible for stepwise linear regression were enrolled for final analysis. For parameters affecting operative efficiency, the fitted model revealed that patients with a pre-operative diagnosis of pheochromocytoma, a higher BMI, and an associated co-morbidity of heart disease are associated with a longer operative time. In addition, the fitted model revealed that patients with a lower post-operative pain score, a delayed oral intake, and a diagnosis of non-functioning adrenal tumor were associated with a lengthier period before returning to normal activity. CONCLUSION: A higher BMI is the only anatomic factor that affects procedural efficiency in LESS adrenalectomy. In addition, post-operative pain score, time to oral intake, and a diagnosis of non-functioning adrenal tumor are the factors affecting patient convalescence.

Endoluminal release of ureteral ligature after hysterectomy.

Iatrogenic ureteral injury is a well-recognized complication of abdominal total hysterectomy. We report a case of a 57-year-old female who underwent abdominal total hysterectomy for a uterine myoma and experienced severe right flank pain postoperatively. The imaging study displayed an obstruction of the right distal ureter. Under ureteroscopy, an extraluminal ligature was released with a holmium:yttrium-aluminum-garnet laser. The stenotic segment was immediately relieved. Two months later, the intravenous urogram illustrated patency of the distal ureter with regression of right hydronephrosis. There was no recurrent hydronephrosis during 1 year of follow-up.

HAS3 underexpression as an indicator of poor prognosis in patients with urothelial carcinoma of the upper urinary tract and urinary bladder.

Via data mining a published transcriptomic database of UBUC (GSE31684), we discovered hyaluronan synthase-3 (HAS3) as the most significant gene stepwise downregulated from early tumorigenesis to progression among those associated with hyaluronan synthase activity (GO:0050501). We consequently analyzed HAS3 protein expression and their association with clinicopathological factors and survival in our well-characterized cohort of urothelial carcinoma of upper urinary tract (UTUC) and urinary bladder (UBUC). HAS3 expression was assessed by immunohistochemistry and evaluated by using H score method in 295 UBUCs and 340 UTUCs, respectively. HAS3 protein expression statuses were further correlated with clinicopathological parameters and evaluated the prognostic significance for disease-specific survival (DSS) and metastasis-free survival (MeFS). HAS3 protein underexpression was significantly associated with advanced pT status, nodal metastasis, high histological grade, vascular invasion, and frequent mitoses in both groups of UCs. HAS3 underexpression not only predicted poorer DSS and MeFS with univariate analysis, but also indicated dismal DSS and MeFS in multivariate analysis. HAS3 underexpression is associated with advanced tumor stage and adverse pathological features, as well as implies inferior clinical outcomes for both groups of patients with UTUCs and UBUCs, suggesting its critical role in tumor progression in UCs and may serve as a prospective prognostic biomarker and a novel therapeutic target in UCs.

GPX2 underexpression indicates poor prognosis in patients with urothelial carcinomas of the upper urinary tract and urinary bladder.

PURPOSE: Oxidative stress is believed to be one of the important etiologies in carcinogenesis that has not been systemically investigated in urothelial carcinoma (UC). Through data mining from a published transcriptomic database of UC of urinary bladders (UBUCs) (GSE31684), glutathione peroxidase 2 (GPX2) was identified as the most significant downregulated gene among those response to oxidative stress (GO:0006979). We therefore analyze GPX2 transcript and protein expressions and its clinicopathological significance. METHODS: Real-time RT-PCR assay was used to detect GPX2 mRNA level in 20 fresh UBUC specimens. Immunohistochemistry was used to determine GPX2 protein expression in 340 urothelial carcinomas of upper tracts (UTUCs) and 295 UBUCs with mean/median follow-up of 44.7/38.9 and 30.8/23.1 months, respectively. Its expression status was further correlated with clinicopathological features and evaluated for its impact on disease-specific survival and metastasis-free survival (MeFS). RESULTS: Decrease in GPX2 transcript level was associated with both higher pT and positive nodal status in 20 UBUCs (all p < 0.05). GPX2 protein underexpression was also significantly associated with advanced pT status, nodal metastasis, high histological grade, vascular invasion, and frequent mitoses in both groups of UCs (all p < 0.05). GPX2 underexpression not only predicted dismal DDS and MeFS at univariate analysis, but also implicated worse DDS (UTUC, p = 0.002; UBUC, p = 0.029) and MeFS (UTUC, p = 0.001; UBUC, p = 0.032) in multivariate analysis. CONCLUSIONS: GPX2 underexpression is associated with advanced tumor status and implicated unfavorable clinical outcome of UCs, suggesting its role in tumor progression and may serve as a theranostic biomarker of UCs.

Ergonomic principles and techniques in facilitating advanced laparoendoscopic single site (LESS) urinary tract reconstruction with conventional laparoscopic instruments.

BACKGROUND/PURPOSE: The technical and ergonomic details of laparoendoscopic single site (LESS) reconstruction have not been reported. In this study, we explored the feasibility and safety of performing advanced LESS upper urinary tract reconstruction with conventional laparoscopic instruments. METHODS: Between September 2010 and March 2011, we retrospectively reviewed prospectively collected data from five patients who underwent LESS urinary tract reconstruction. The LESS reconstruction included pyeloureterostomy (N = 1), dismembered pyeloplasty (N = 2), ureteroneocystostomy (N = 1), and ureteroplasty for bifid blind ending ureter (N = 1). The perioperative and postoperative parameters were collected for analysis. The ergonomic principles and techniques are detailed. RESULTS: All reconstructive LESS procedures were completed successfully without open conversion or laparoscopic conversion. Ancillary ports or ancillary instruments were not applied in any of the patients. The mean patient age was 40.4 years. The mean operative time was 213 ± 69 minutes, the estimated blood loss ranged from minimal to 50 mL, and the mean hospital stay was 4.4 ± 4 days. No operation-related complication occurred. CONCLUSION: Based on our ergonomic principles and suturing/knotting techniques, conventional laparoscopic instruments are feasible and safe for LESS urinary reconstructive procedures.

Lutein inhibits the migration of retinal pigment epithelial cells via cytosolic and mitochondrial Akt pathways (lutein inhibits RPE cells migration).

During the course of proliferative vitreoretinopathy (PVR), the retinal pigment epithelium (RPE) cells will de-differentiate, proliferate, and migrate onto the surfaces of the sensory retina. Several studies have shown that platelet-derived growth factor (PDGF) can induce migration of RPE cells via an Akt-related pathway. In this study, the effect of lutein on PDGF-BB-induced RPE cells migration was examined using transwell migration assays and Western blot analyses. We found that both phosphorylation of Akt and mitochondrial translocation of Akt in RPE cells induced by PDGF-BB stimulation were suppressed by lutein. Furthermore, the increased migration observed in RPE cells with overexpressed mitochondrial Akt could also be suppressed by lutein. Our results demonstrate that lutein can inhibit PDGF-BB induced RPE cells migration through the inhibition of both cytoplasmic and mitochondrial Akt activation.

A comparison of the Trachway intubating stylet and the Macintosh laryngoscope in tracheal intubation: a manikin study.

PURPOSE: The Trachway intubating stylet (Trachway(®)), when used by experienced anesthesiologists, has been shown to be effective for difficult airway management. We evaluated the efficacy of this intubating stylet for tracheal intubation in a manikin when used by experienced laryngoscopists with little experience using this device. METHODS: Thirty-eight nurse anesthesiologists intubated the trachea of a manikin (Laerdal Airway Management Trainer) with a Trachway intubating stylet or a Macintosh laryngoscope in easy and difficult laryngoscopy scenarios. The duration of the intubation attempts, success rates, dental trauma, and ease of use (0 = very easy; 10 = very difficult) were recorded. The primary endpoint was the duration of the successful tracheal intubation attempt in the difficult laryngoscopy scenario. Data are presented as means (SD). RESULTS: Both devices resulted in similar tracheal intubation performance in the easy laryngoscopy scenario. However, the Trachway intubating stylet provided shorter intubation times (20.8 ± 5.6 vs. 25.5 ± 7.3 s; p = 0.003) and easier intubations (2.4 ± 1.6 vs. 5.7 ± 1.8; p < 0.001) compared with the Macintosh laryngoscope in the difficult laryngoscopy scenario. All tracheal intubations were successful and no dental trauma was observed when using the Trachway intubating stylet. CONCLUSION: We concluded that the Trachway intubating stylet, when used by novices, is effective in both easy and difficult laryngoscopy scenarios. In difficult laryngoscopy scenarios, this device provided faster, easier, and less traumatic intubation than the Macintosh laryngoscope.

Ergonomic and geometric tricks of laparoendoscopic single-site surgery (LESS) by using conventional laparoscopic instruments.

BACKGROUND: The aim of this study was to explore the feasibility and safety of performing laparoendoscopic single-site surgery (LESS) with conventional laparoscopic instruments. METHODS: We retrospectively reviewed our data from 175 patients who underwent various urological LESS procedures via the same ergonomic and geometric principles between 2008 and 2011. LESS procedures performed included adrenalectomy (N = 23), radical nephrectomy (N = 5), radical nephroureterectomy with bladder cuff resection (N = 5), varicocelectomy (N = 12), nephropexy (N = 4), lumbar sympathectomy (N = 4), orchiectomy for intra-abdominal testis (N = 1), pyeloureterostomy (N = 1), dismembered pyeloplasty (N = 1), and adult inguinal hernia mesh repair (N = 119). RESULTS: All procedures were completed successfully without the use of ancillary ports or articulating instruments except two cases that required laparoscopic conversion. The mean patient age was 48.9 years. Mean operative time was 99.7 min, mean estimated blood loss was 17.3 ml, and mean hospital stay was 2.1 days. There were no intraoperative complications. CONCLUSION: According to our ergonomic and geometric principles, use of conventional laparoscopic instruments is feasible and safe in LESS procedures.

A comparative study of multiport versus laparoendoscopic single-site adrenalectomy for benign adrenal tumors.

BACKGROUND: The safety and feasibility of laparoendoscopic single-site (LESS) adrenalectomy for benign adrenal lesions was proved in early clinical series. However, the advantages of LESS over multiport laparoscopic adrenalectomy still are under investigation. METHODS: Since October 2009, the authors have prospectively performed LESS retroperitoneal adrenalectomy for 21 consecutive patients with benign adrenal tumors (LESS group). Another 28 patients with benign adrenal tumors were prospectively collected between June 2006 and October 2009 and served as a multiport laparoscopic adrenalectomy group. The patients' demographic data, operating time, estimated blood loss, peri- and postoperative complications, and short-term outcome were collected for further analysis. RESULTS: The demographic data were comparable between the two groups in terms of the patient age, gender, body mass index (BMI), laterality, diagnosis, and resected specimen weight. No major complication or mortality occurred in either group. Neither group had any conversions. No differences were observed between the two groups in terms of intraoperative hemodynamic status or peri- or postoperative complications. The LESS patients had quicker resumption of oral intake (0.18 vs 1 day; p < 0.001), a shorter hospital stay (2 vs 4 days; p < 0.001), and a reduced analgesic requirement postoperatively (0 vs 0.84 mg/kg; p = 0.023) than the multiport laparoscopic patients. CONCLUSIONS: The results demonstrate that LESS adrenalectomy is as safe and effective as conventional multiport laparoscopic adrenalectomy for benign adrenal tumors. In addition, LESS adrenalectomy provides short-term convalescence advantages over multiport laparoscopic adrenalectomy.

Comparison of health-related quality of life between subjects treated with radical prostatectomy and brachytherapy.

AIMS AND OBJECTIVES: To evaluate the symptoms and self-assessment of quality of life in men with localised prostate cancer after having had a radical prostatectomy or brachytherapy treatment. BACKGROUND: Prostate cancer is a significant growing disease among men in Taiwan. Quality of life issues for the men who are living with this disease and the consequences of treatment. DESIGN: A postal questionnaire survey. METHODS: The study population came from one 1170-bed hospital in Kaohsiung County, Taiwan. Data was collected from 20 August 2007-20 November 2009. Seventy-eight men met the inclusion criteria. The researchers mailed a survey to each participant, which they completed at home and returned in a pre-stamped, addressed envelope. Sixty-four subjects participated and self-reported using a structured questionnaire. The reliability of overall prostate cancer index was 0.90 and 0.85, 0.93 and 0.72 for each subscale, respectively. RESULTS: The results indicate that the number of months post-treatment was positively correlated with urinary function and age was negatively correlated with sexual, bowel function and bowel bothers. One predictor (month post-treatment) was related to urinary function; one predictor (treatment method) was related to bowel function and four predictors (marital status, age, treatment method and month post-treatment) were related to sexual function. Findings showed that patients who received brachytherapy have better urinary functions, as compared with prostatectomy patients. CONCLUSION: Study findings suggest that healthcare providers should have a better understanding of patients' complications after treatment and this can ultimately raise the quality of life for prostate cancer patients. RELEVANCE TO CLINICAL PRACTICE: The impact of quality of life among post prostate cancer treatment is common. Urological nurses should therefore take the responsibility regarding the consequence of urinary incontinence and sexual function and seeking appropriate nursing interventions for these complications.

Small interfering RNA targeting N-cadherin regulates cell proliferation and migration in enzalutamide-resistant prostate cancer.

Enzalutamide is one of the options for treating patients with castration-resistant or metastatic prostate cancer. However, a substantial proportion of patients become resistant to enzalutamide after a period of treatment. Cells in these tumors typically exhibit increased proliferative and migratory capabilities, in which N-cadherin (CDH2) appear to serve an important role. In the present study, by up- and downregulating the expression of CDH2, the possible effects of CDH2 on the prostate cancer cell line LNCaP were investigated. Male sex hormone-sensitive LNCaP cells treated with 10 µM enzalutamide were named LNCaP enzalutamide-resistant (EnzaR) cells. Reverse transcription-PCR, western blotting and immunofluorescence staining were used to measure CDH2, E-cadherin, α-SMA, Snail and Slug expression. Transfection with the pCMV-CDH2 plasmid was performed for CDH2 upregulation, whilst transfection with small interfering RNA (siRNA)-CDH2 was performed for CDH2 downregulation. MTT and Cell Counting Kit-4 assays were used to evaluate the proportion of viable cancer cells. Subsequently, gap closure assay was performed to evaluate the migratory capability of both LNCaP and LNCaP EnzaR cell lines. CDH2 expression was found to be increased in LNCaP EnzaR cells compared with that in LNCaP cells. CDH2 overexpression increased cell viability and migration in both LNCaP and LNCaP EnzaR cell lines. By contrast, the opposite trend was observed after CDH2 expression was knocked down. CDH2 expression also showed a high association with that of four epithelial-mesenchymal transition markers, which was confirmed by western blotting. Based on these results, it was concluded that knocking down CDH2 expression using siRNA transfection mediated significant influence on LNCaP EnzaR cell physiology, which may be a potential therapeutic option for prostate cancer treatment.

Minilaparoscopic varicocelectomy with preservation of testicular artery and lymphatic vessels by using intracorporeal knot-tying technique: five-year experience.

BACKGROUND: In this study we present our experience using minilaparoscopic intracorporeal knot tying to ligate internal spermatic veins (ISV) while sparing the spermatic artery and lymphatics. METHODS: Minilaparoscopic varicocelectomies were performed in 87 patients between January 2004 and January 2009. All varicoceles were detected clinically according to the World Health Organization (WHO) classification and confirmed by scrotal color Doppler ultrasonography. The surgical indications were scrotal symptoms in 71, infertility in 16, and both conditions in 2. Three 3.5 mm minilaparoscopic ports were used for the operation. The ISVs were dissected and then ligated with intracorporeal knot-tying. The testicular artery and lymphatic vessels were carefully preserved to minimize procedure-related complications. RESULTS: Unilateral laparoscopic varicocelectomy was performed in 21 (24.2%) patients and bilateral in 66 (75.8%). Mean operative time was 71.1 ± 29.2 and 46.8 ± 12.6 min for bilateral and unilateral varicocelectomies, respectively. All patients were discharged within 24 h after surgery. Neither immediate major nor late procedure-related complications were noted. Of the 71 patients with scrotal symptoms, the symptoms completely subsided in 55 (77.5%) and partially subsided in 10 (14.1%). Only one (1.2%) recurrent varicocele was detected within a mean follow-up of 21 months (range = 3-42). Neither hydrocele formation nor testicular atrophy was found during the follow-up period. CONCLUSION: Our 5-year experience revealed that minilaparoscopic varicocelectomy with sparing of artery and lymphatic vessels could safely and effectively ligate all spermatic veins and preserve spermatic arteries and lymphatic channels without leading to a high varicocele persistence or recurrence.

Melanogenesis inhibitory activity of two generic drugs: cinnarizine and trazodone in mouse B16 melanoma cells.

More than 200 generic drugs were screened to identify the inhibitory activity on melanogenesis in mouse B16 melanoma cells. Cinnarizine and trazodone were identified as melanogenesis inhibitors. The inhibitory effects of the two drugs on cell survival, melanogenesis, and tyrosinase activity were investigated. The results showed that both cinnarizine and trazodone inhibited melanogenesis in B16 cells by a dose-dependent manner at the non-cytotoxic concentrations. Based on the results of the present study, seeking new melanogenesis inhibitors from generic drugs is an alternative approach to developing new depigmenting agents in cosmeceuticals. Moreover, cinnarizine and trazodone were proven to be good candidates as skin-whitening agents for treatment of skin hyperpigmentation.

Topical lidocaine improves conditions for laryngeal mask airway insertion.

PURPOSE: We hypothesized that optimal laryngeal mask airway (LMA) insertion conditions might be achieved with topical lidocaine and a smaller dose of propofol. In this study, insertion conditions after topical lidocaine 40 mg followed by propofol 2 mg.kg(-1) were compared with propofol 2 mg.kg(-1) or propofol 3 mg.kg(-1) alone. METHODS: Ninety patients were recruited for this randomized prospective double-blind study. One group received four sprays of topical lidocaine (40 mg) over the posterior pharyngeal wall followed by propofol 2 mg.kg(-1) (Group 2PL; n = 30). The other two groups received four sprays of 0.9% normal saline followed by propofol 2 mg.kg(-1) (Group 2P; n = 30) or by propofol 3 mg.kg(-1) (Group 3P; n = 30). The frequency of optimal insertion conditions (successful insertion at the first attempt without adverse responses) and side effects were recorded. RESULTS: The frequency of optimal insertion conditions was greater in Group 2PL (20/30, 67%) and Group 3P (22/30, 73%) than in Group 2P (11/20, 37%) (P = 0.009). In Group 3P, the mean blood pressure was lower than in the other groups prior to LMA-Classic insertion (P = 0.003) but was similar after insertion. The incidence of apnea was greater in Group 3P patients (17/30, 57%) than in Group 2P (2/30, 7%) or Group 2PL patients (1/30, 3%) (P < 0.001). CONCLUSION: Topical lidocaine 40 mg followed by propofol 2 mg.kg(-1) can provide optimal insertion conditions of the LMA-Classic comparable to those of propofol 3 mg.kg(-1), with fewer hemodynamic changes and a lower incidence of apnea.

Surgical treatment for urinary incontinence after prostatectomy: A meta-analysis and systematic review.

BACKGROUND: This meta-analysis was designed to assess the efficacy of the male sling and artificial urinary sphincter on treating post-prostatectomy incontinence by evaluating daily pad use, cure rate, frequency of improvement in incontinence, and quality of life. METHODS: Medline, Cochrane, Google Scholar, and ClinicalTrials.gov were searched (until March 31, 2014) for studies that investigated the effectiveness of artificial urinary sphincter or sling surgical treatments for prostate cancer. The primary outcome was daily pad use before and after surgery and secondary outcomes were quality of life before and after surgery, and frequency of cures (no need to use of a pad for at least 1 day) and improvements (decreased pad usage) in incontinence after surgery. RESULTS: We found that that both the sling and artificial urinary sphincter significantly decreased the number of pads used per day by about 3 (P-values <0.001) and increased the quality of life compared with before intervention (P-values < 0.001). In addition, the cure rate and was around 60%. Intervention resulted in improvement in incontinence by about 25% (P < 0.001). CONCLUSION: Our findings indicate that both sling and artificial urinary sphincter interventions are effective in reducing incontinence and improving the patient's quality of life.

Prognostic Impact of Thrombospodin-2 (THBS2) Overexpression on Patients with Urothelial Carcinomas of Upper Urinary Tracts and Bladders.

PURPOSE: Urothelial carcinoma (UC) is a type of tumor, especially of the urinary bladder, that affects people worldwide. Clarification of its detailed tumor biology and discovery of potential targets for developing treatment strategies are imperative because of frequent recurrences and poor prognosis of advanced UCs. By data mining a published dataset of UC of bladder (UCB) transcriptome (GSE31684) from Gene Expression Omnibus, National Center of Biotechnology Information (GEO, NCBI), we identified that THBS2 was the most significantly upregulated gene among those related to structural molecule activity (GO:0005198). Therefore, we evaluated the clinical significance and prognostic impact of thrombospondin-2 (THBS2) protein, A.K.A. TSP2, which encoded by THBS2 gene. MATERIALS AND METHODS: THBS2 immunostaining was performed in 340 UCs of upper urinary tract (UC-UUTs) and 295 UCBs; subsequently, both groups were dichotomized into high- and low-expression subgroups. Moreover, statistical analyses were performed to correlate the association between THBS2 expression and clinicopathological parameters with two survival indexes: disease-specific survival (DSS) and metastasis-free survival (MeFS). RESULTS: High THBS2 immunoexpression was significantly associated with advanced primary tumor status, nodal metastasis, and vascular invasion in both UC-UUT and UCB groups (all P ≤ .001). In addition, THBS2 overexpression was linked to adverse DSS and MeFS in univariate analyses and served as an independent prognosticator indicating poor outcomes in both groups in multivariate analyses. CONCLUSION: THBS2 may play a crucial role in UC progression and may be a novel prognostic marker. Additional investigations to elucidate the molecular pathway are necessary for developing potential THBS2-targeted therapies for UCs.

Complement Component 1, s Subcomponent Overexpression is an Independent Poor Prognostic Indicator in Patients with Urothelial Carcinomas of the Upper Urinary Tract and Urinary Bladder.

PURPOSE: Urothelial carcinoma of the urinary bladder and upper tract is prevalent. By subjecting a documented transcriptome data set of urothelial carcinoma of bladder (GSE31684) to data mining and focusing on genes linked to peptidase activity (GO:0008233), we recognized C1S as the most significantly upregulated gene related to an advanced tumor status and metastasis. We subsequently analyzed the association of both C1S mRNA and its encoded protein expression with the clinical and pathological significance. MATERIALS AND METHODS: We used real-time reverse transcription polymerase chain reaction to detect C1S transcription levels in 20 cases each of urothelial carcinoma of bladder and upper tract. An immunohistochemical stain was conducted to determine C1s protein expression levels in patients with urothelial carcinoma of upper tract (n = 340) and urinary bladder (n = 295). Furthermore, we examined the correlation of C1s expression with clinicopathological characteristics, disease-specific survival, and metastasis-free survival. RESULTS: C1S transcription levels were significantly high in patients with advanced-stage tumors of both groups (all P < .05). Immunohistochemical analysis revealed that C1s expression levels were significantly associated with adverse clinicopathological parameters in both groups of urothelial carcinoma (all P < .05). C1s overexpression predicted poor disease-specific and metastasis-free survival rates for both urothelial carcinoma groups in the univariate analysis, and it was also an independent prognostic factor in the multivariate analysis (all P < .05). CONCLUSIONS: C1s may play a pivotal role in urothelial carcinoma progress and can represent a vital prognostic marker and a promising new therapeutic target in urothelial carcinoma.

CDCA5 overexpression is an indicator of poor prognosis in patients with urothelial carcinomas of the upper urinary tract and urinary bladder.

AIMS: Urothelial carcinoma (UC) is the most common tumor involving upper urinary tract (UTUC) and urinary bladder (UBUC) whose molecular survival determinants remains obscured. By computerizing a public transcriptomic database of UBUCs (GSE32894), we identified cell division cycle associated 5 (CDCA5) as the most significantly upregulated gene among those associated with G1-S transition of the mitotic cell cycle (GO:0000082). We therefore analyzed the clinicoptaological significance of CDCA5 expression in our well-characterized UC cohort. METHODS AND RESULTS: Quantigene assay was used to detect CDCA5 transcript levels in 36 UTUCs and 30 UBUCs. We used immunohistochemistry evaluated by H-scores to determine CDCA5 protein expression in 295 UBUCs and 340 UTUCs, respectively. CDCA5 expression was further correlated with clinicopathological features and disease-specific survival (DSS) and metastasis-free survival (MeFS). For both groups of UCs, increments of CDCA5 transcript levels were associated with higher pT status, CDCA5 protein overexpression was also significantly associated with advanced pT status, nodal metastasis, high histological grade, vascular invasion, and frequent mitoses. CDCA5 overexpression was predictive for worse DSS and MeFS in univariate and multivariate analysis. CONCLUSIONS: CDCA5 overexpression is associated with advanced clinical features of UC, suggesting its potential value as a prognostic biomarker and a novel therapeutic target.