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Background and Objectives : The incidence of urothelial cancer in males is higher than in females; however, females have a higher risk of recurrence and progression. The aim of our study was to report the effect of gender on the oncological outcome in advanced urothelial cancer. Materials and Methods : In our retrospective study, all patients had undergone primary surgical treatment for urothelial cancer and were affected by stage IV disease at the time of chemotherapy. Response to therapy and toxicity were evaluated. Subgroups were analyzed for tumour presentation, first- and second-line treatment response, progression-free survival (PFS) and overall survival (OS). Results. Seventy-five patients, 18 (24%) females and 57 (76%) males, were considered. Investigation into the distribution of individual characteristics according to gender revealed a significant difference only for smoking, with a prevalence of smokers in women ( p = 0.029). At the end of follow-up, OS was higher in females (27.5% vs. 17.4%; p = 0.047). Smoking did not significantly influence OS ( p = 0.055), while univariate Cox regression analysis confirmed that males had a higher risk of death (HR = 2.28, 95% CI 0.99-129 5.25), with borderline statistical significance ( p = 0.053). Men showed higher PFS than women both after first-line ( p = 0.051) and second-line chemotherapy ( p = 0.018), with a lower risk of progression (HR = 0.29, 95% CI 0.10-0.86; p = 0.026). No differences were found between genders with regard to toxicity. Conclusions. In our series, PFS rates following first- and second-line therapies for advanced urothelial carcinoma confirmed that females have a greater risk of progression than males.

After radical cystectomy or pathologies affecting the ureter(s), bowel segments can be employed to restore the natural urine flow or to create an external urinary diversion. Nevertheless, the interposition of bowel segments in the urinary tract is not devoid of complications. In fact, bowel's microstructure differs from the urothelium; specifically its mucosa is aimed at reabsorption, rather than storage. The aim of this paper is to revise the pathophysiology of complications related to bowel's mucosal properties. Those are: metabolic imbalance, malabsorption of vitamins, cholelitiasis, nephrolitiasis and infections. Their entity varies according to the segment used and to its length, which reflects the surface in contact with urine. Mostly, they occur on the long-term, but metabolic imbalances might occur soon after surgery as well., (Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Objectives: To present our experience with a sigmoid orthotopic neobladder., Methods: We retrospectively evaluated the functional and oncological outcomes of 160 patients who underwent orthotopic neobladder reconstruction using a detubularized 20-25-cm sigmoid segment at our institution. Each patient was evaluated every 3 months the first year, every 6 months for the next 4 years and annually thereafter. Urodynamic studies of all consenting patients were carried out after 6 months, and 2, 5 and 10 years. We carried out the log-rank test, and used Cox regression models and Kaplan-Meier survival analysis. The anova test was used to compare urodynamic findings over time., Results: Mean follow up was 6.8 years (range 0.65-21.7 years). Overall survival was 58.1% at 5 years, and 47.1% at 10 years. Early complications occurred in 36 patients (22.6%); late complications in 40 (25%). Stage V chronic kidney disease developed in two patients (1.3%). Complete (daytime and night-time) continence, defined as no need for pads or condom devices, was achieved by 45% of patients at 5 years, daytime continence was achieved by just 36% of patients; both were unchanged at 10 years. A significant difference emerged in maximal neobladder capacity and post-void residual values between 6 months and 2 years, and between 2 and 5 years (P < 0.01 and P = 0.03, respectively)., Conclusions: Sigmoid neobladder continence and capacity significantly improve over the first 5 years, and they remain stable over the long term. Upper urinary tract function is not affected by endoluminal pressure, and the rate of metabolic imbalance is negligible., (© 2016 The Japanese Urological Association.)

Background: To identify molecular biomarkers for tumor diagnosis and monitoring of disease progression, several noninvasive tests on liquid biopsy have been proposed for different cancers including those of urogenital origin. Among biomarkers, carbonic anhydrase IX (CAIX) has gained attention as it regulates extracellular pH and induces cytoplasmic alkalization contributing to malignant progression and poor treatment outcome. Works on tissues suggested the potential use of CAIX as a tumor biomarker for urogenital malignancies, but only few studies have been performed on its detection in urine., Scope: The aim of the present study is the measurement of CAIX messenger RNA (mRNA) in urine sediments of patients affected by kidney, prostate, and bladder cancers to evaluate the clinical sensitivity and specificity of the test., Procedures: The quantification of the total CAIX mRNA concentration and of its full-length isoform (CAIX FL) have been performed by reverse transcription quantitative polymerase chain reaction (RT-qPCR) on RNA extracted from urine sediments of patients affected by urogenital cancers., Results: Urinary total CAIX mRNA expression resulted to be lower in patients with kidney and prostate cancer in comparison with the control group, but no statistically significant difference could be evidenced for bladder cancer. The evaluation of the relative percentage of FL isoform mRNA (FL%) showed a significant increase of FL% in urine from patients with cancer (median = 70.8%) in comparison with the healthy subjects (median = 2.6%) and this finding was confirmed for each cancer type separately. The comparison among receiver operating characteristic curves for total CAIX mRNA, CAIX FL mRNA, and FL% indicated that FL% shows the best diagnostic performance with 90% sensitivity and 72% specificity. Comparison of the results obtained in urine with those found in the corresponding tissues indicated 80% concordance., Conclusions: The CAIX mRNA expression in urine sediments can be considered a surrogate marker of CAIX expression in tumor tissues of urogenital origin. In particular, the analysis of FL% possesses the best characteristics to be a suitable noninvasive biomarker for urogenital cancer diagnosis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: In human cancers, carbonic anhydrase IX (CAIX) influences cell proliferation and tumor progression, maintaining intracellular and extracellular pH under hypoxic conditions. An alternative CAIX isoform, lacking of exons 8-9 (AS) and independent from the levels of hypoxia, was recently demonstrated in cancer cells. AS-CAIX competes with the full-length (FL) isoform in the regulation of the extracellular pH, mainly in a mild hypoxic status. In the present study, we evaluated mRNA expression of the 2 CAIX isoforms and their clinical relevance in bladder cancers and urine sediments., Materials and Methods: We measured mRNA expression of FL- and AS-CAIX isoforms in tumor tissues and benign mucosa from 45 patients with bladder transitional cell carcinoma. The expression of the 2 isoforms was also measured in urine sediment of 81 bladder cancer patients and 93 control subjects., Results: Expression of FL-CAIX mRNA was lower than AS-CAIX in benign mucosa (P = 0.006) whereas in paired bladder cancers FL-CAIX mRNA was higher (P = 0.007). Consequently, the percentage of FL-CAIX in bladder cancers [median: 62.6%] was significantly higher than in benign mucosa [15.0%] (P < 0.0001). In the urinary sediments of bladder cancer patients FL-CAIX mRNA was significantly higher in comparison with normal controls (P = 0.003). FL-CAIX percentage appeared dramatically higher in urine sediments of bladder cancer patients [64.5%] in comparison with controls [7.5%] (P < 0.0001). In addition, FL-CAIX% was significantly different in sediments from pTa-pT1 and ≥ pT2 patients [51.5% and 91.7%, respectively] (P = 0.016). Stratification according tumor grade indicated that FL-CAIX% was significantly lower in G1 bladder cancers [33.3%] in comparison with G2-G3 [88.6%] (P = 0.005) The clinical sensitivity for FL-CAIX% in urine sediments was 0.93, with a 0.76 specificity. Using the same cut-off positive predictive value (PPV) was 0.78, whereas negative predictive value (NPV) was 0.93., Conclusions: Our results seem to indicate that in bladder cancers and related urine sediments, FL-CAIX is the prevalent and is the most accurate clinically relevant variant surrogate of hypoxic stress., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objectives: Urinary hypermethylation of BCL2, hTERT, and DAPK promoters has been previously demonstrated as an accurate biomarker for the detection of urothelial carcinoma of the bladder (UCB) in patients undergoing radical cystectomy. In the present study, we investigated with a validation intent the frequency and levels of methylation of the same 3 genes in tumor tissue and urine sediment of patients undergoing transurethral resection (TUR) for non-muscle-invasive (NMI) UCB., Materials and Methods: A total of 108 consecutive patients with NMI UCB and 105 controls with no genitourinary malignancies were enrolled in this prospective study conducted in 2 tertiary referral academic urological departments with an advanced molecular laboratory. The frequency and levels of methylated BCL2, hTERT, and DAPK promoters were evaluated with quantitative methylation-specific real-time polymerase chain reaction in DNA extracted from tumor tissue and paired normal bladder mucosa retrieved at the time of TUR in patients, and from urine in patients and controls., Results: In tumor tissue, at least 1 gene was hypermethylated in 91% patients (BCL2 in 62%, hTERT in 53%, DAPK in 48%). Methylation of hTERT was significantly correlated with tumor grade (P = 0.026). In urine sediment sensitivity and specificity were 76% and 98%, respectively, using BCL2 and hTERT. The number of methylated genes was highly correlated with tumor grade (P = 0.005). Methylated BCL2 and hTERT in urine sediment were highly correlated with those of the corresponding bladder tumor qualitatively (P < 0.001), and only BCL2 also quantitatively (P = 0.005). Methylation levels of BCL2 and hTERT were variably associated with tumor grade and stage, but were significantly correlated with patient age (P = 0.004 and P = 0.027, respectively)., Conclusions: These findings suggest that quantitative methylation analysis of BCL2 and hTERT, but not DAPK, in urine sediment may be a useful tool in the diagnosis of NMI UCB, deserving future applicability studies., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To report the oncological outcome of 106 patients who had locally advanced prostate cancer with microscopic bladder neck invasion, identified in a series of 1129 patients surgically treated with retropubic radical prostatectomy over a 12-year period., Patients and Methods: All specimens were reviewed. Microscopic bladder neck invasion was defined as the presence of neoplastic cells within the smooth muscle bundles of the bladder neck, with no accompanying prostatic glandular tissue on the corresponding slide. Survival was analysed for different subgroups in relation to several variables., Results: The follow-up (median 7.2 years, mean 6.68, range 0.3-14) was available for 106 patients with microscopic bladder neck invasion. Seminal vesicle invasion was present in 69.8% of the cases, lymph node involvement in 29.2%, apex infiltration in 31.8%, and positive surgical margins in 23.6%. Biochemical progression occurred in 61 (57.5%) patients, and 25 of them died from cancer. The mean (sd) biochemical progression-free survival was 0.68 (0.05), 0.59 (0.05), 0.40 (0.05) and 0.38 (0.05) at 1, 2, 5 and 10 years, respectively. Age, Gleason score and lymph node invasion were independent prognostic factors on multivariate analysis. Overall and cancer-specific survival rates were 0.75 (0.04) and 0.80 (0.04) at 5 years and 0.57 (0.04) and 0.75 (0.04) at 10 years, respectively. Univariate analysis showed that seminal vesicle invasion, lymph node involvement and surgical Gleason score > or =8 significantly increased the risk of death. On multivariate analysis only the surgical Gleason score had an independent prognostic role with regard to overall survival (P = 0.01; odds ratio 2.82, 95% confidence interval 1.2-6.4) and cancer-specific survival (P < 0.001; 8.6, 2.5-28.8)., Conclusions: In this series, overall and cancer-specific survival rates were comparable to those reported for surgically treated cT3 prostate cancers. The lack of need for external urinary diversion during the entire follow-up significantly contributed to the patients' quality of life.

Actinomycosis of the urinary bladder is rare, mostly subsequent to abdomino-pelvic infection, and usually affects women with long-term use of an intrauterine device. We describe a case of vesical actinomycosis mimicking a papillary bladder tumour in a 56-year-old woman with primary manifestation of the disease in the genital tract, subjected to two transurethral resections after relapse of a polypoid mass in the bladder. Urological procedures are necessary to differentiate actinomycosis from bladder cancer and the diagnosis is often made histologically., (Copyright © 2010 S. Karger AG, Basel.)

Background: The enzyme tankyrase-1 (TNKS-1), a member of the growing family of poly(ADP-ribose) polymerases (PARPs), was identified as a component of the human telomeric complex. PARPs catalyze the formation of long chains of poly(ADP-ribose) onto protein acceptors using NAD(+) as a substrate. TNKS-1 interacts with the telomeric DNA-binding protein TTAGGG repeat-binding factor 1 (TRF1), which is a negative regulator of telomere length. TNKS-1 is a positive regulator of telomere elongation and its activity appears to be upregulated in some human cancers., Methods: We evaluated for the first time TNKS-1 mRNA expression by real time RT-PCR in tumor tissue, paired normal mucosa and urine sediment in patients with transitional cell carcinoma (TCC) of the bladder. Samples were collected from 41 consecutive patients, 20 with non-muscle-invasive (pTa-pT1) and 21 with muscle-invasive (>/=pT2) bladder TCC. Results obtained in urine sediment were compared with those from 40 healthy subjects matched for age and sex., Results: In pTa-pT1 tumor tissues, TNKS-1 mRNA levels were significantly higher than in >/=pT2 patients (p<0.0001). In urine sediment from TCC patients, independent of tumor stage, TNKS-1 mRNA levels were significantly higher than in healthy controls, with maximal levels in >/=pT2 patients. In particular, TNKS-1 mRNA levels in urine were elevated in 31/41 patients with a sensitivity of 81% in >/=pT2 tumors and 65% in pTa-pT1 TCC. Of patients with pTa-pT1 tumors, 11 had a recurrence within 18 months after initial transurethral resection. In these patients, urine levels of TNKS-1 mRNA were higher than in non-relapsing patients (p=0.038)., Conclusions: In this preliminary study, TNKS-1 mRNA in urine sediment from patients with bladder TCC correlated with tumor stage, and higher preoperative levels were associated with increased risk of early recurrence.