Prognostic significance of 18F-FDG PET/CT indices in metastatic renal cell cancer and evaluation of revised IMDC risk model by including 18F-FDG PET-CT parameters.

BACKGROUND: Prognostic markers in metastatic renal cell cancer (mRCC) are still insufficient. Any prognostic model objectively determines disease burden. PURPOSE: To investigate the relationship between 18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) parameters and outcomes in mRCC, and to define a revised International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model for the intermediate-risk group. MATERIAL AND METHODS: A retrospective study of mRCC was conducted. To investigate the prognostic significance of 18F-FDG PET/CT parameters, maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), and metabolic tumor volume (MTV) were determined in pre-treatment images. Cutoff values were defined by ROC curve analyses and their association with outcomes was analyzed. Additionally, a TLG-adjusted IMDC model was created by stratifying intermediate-risk group patients according to TLG levels. RESULTS: The study included 52 patients. The disease control rate (DCR) was 61.5% and median overall survival (OS) was 18 months (95% confidence interval=9.2-25.8). In the univariate analyses, IMDC score, MTV, and TLG were prognostic factors for Disease Control Rate (DCR), and Eastern Cooperative Oncology Group (ECOG)-Performance Status (PS), IMDC score, lactate dehydrogenase (LDH), treatment option, MTV, and TLG were prognostic factors for OS (P < 0.05 each). In the multivariate analyses, MTV was an independent prognostic factor for DCR, and ECOG-PS, LDH, IMDC score, and TLG were independent prognostic factors for OS. According to the revised-IMDC model, the intermediate-favorable group showed longer OS than the intermediate-unfavorable group. CONCLUSION: Pretreatment MTV was independent prognostic factor for DCR and ECOG-PS, LDH, IMDC score, and TLG were independent prognostic factors for OS. Revised-IMDC model could identify patients with a worse prognosis among the IMDC intermediate-risk group.

Ta grade 3/high grade non-invasive bladder cancer: Should we perform a second TUR?

PURPOSE: To evaluate the effect of second transurethral resection (TUR) on oncological outcomes, according to the presence or absence of detrusor muscle in the initial TUR of patients with pTa Grade 3/high grade (G3/HG) tumours, who received at least 1 year of maintenance Bacillus Calmette-Guerin (BCG) therapy. PATIENTS AND METHODS: In this retrospective study, we evaluated the effect of second TUR on oncological outcomes of 93 patients with pTa G3/HG tumours, according to the presence or absence of muscle in the initial TUR. All patients received maintenance BCG therapy according to the SWOG protocol. RESULTS: Median follow-up was 36 months. If muscle is present in the initial TUR, a second TUR significantly increased median time to first recurrence, compared to those without a second TUR (77.6 vs 36.9 mos, P = .0086). If muscle is missing in the initial TUR, a second TUR significantly decreased recurrence rate (20% vs 66.7%, P = .002), increased median time to first recurrence (78.9 vs 42.7 mos, P = .0001) and median time to progression (22 vs 7 mos, P = .05), compared to those without a second TUR. CONCLUSION: In patients with pTa G3/HG tumours, if the muscle is missing in the initial TUR, a second TUR should be performed in order to attain lower recurrence rates and longer median time to recurrence and progression. If the muscle is present in the initial TUR, a second TUR will only increase median time to first recurrence.

The Effect of Diagnostic Ureterorenoscopy on Intravesical Recurrence in Patients Undergoing Nephroureterectomy for Primary Upper Tract Urinary Carcinoma.

OBJECTIVE: The objective of this study is to evaluate the effect of diagnostic ureterorenoscopy (URS) prior to radical nephroureterectomy (RNU) on intravesical recurrence (IVR), in patients with primary upper urinary tract urothelial carcinoma (UTUC). MATERIALS AND METHODS: Retrospective analysis of 354 patients, who underwent RNU for UTUC from 10 urology centers between 2005 and 2019, was performed. The primary endpoint was the occurrence of IVR after RNU. Patients were divided into URS prior to RNU (Group 1) and no URS prior to RNU (Group 2). Rates of IVR after RNU were compared, and a Cox proportional hazards model was used to evaluate potential predictors of IVR. RESULTS: After exclusion, a total of 194 patients were analyzed: Group 1 n = 95 (49.0%) and Group 2 n = 99 (51.0%). In Group 1, a tumor biopsy and histopathological confirmation during URS were performed in 58 (61.1%). The mean follow-up was 39.17 ± 39.3 (range 12-250) months. In 54 (27.8%) patients, IVR was recorded after RNU, and the median recurrence time within the bladder was 10.0 (3-144) months. IVR rate was 38.9% in Group 1 versus 17.2% in Group 2 (p = 0.001). In Group 1, IVR rate was 43.1% in those undergoing intraoperative biopsy versus 32.4% of patients without biopsy during diagnostic URS (p =0.29). Intravesical recurrence-free survival (IRFS) was longer in Group 2 compared to Group 1 (median IRFS was 111 vs. 60 months in Groups 2 and 1, respectively (p< 0.001)). Univariate analysis revealed that IRFS was significantly associated with URS prior to RNU (HR: 2.9, 95% CI 1.65-5.41; p < 0.001). In multivariate analysis, URS prior to RNU (HR: 3.5, 95% CI 1.74-7.16; p < 0.001) was found to be an independent prognostic factor for IRFS. CONCLUSION: Diagnostic URS was associated with the poor IRFS following RNU for primary UTUC. The decision for a diagnostic URS with or without tumor biopsy should be reserved for cases where this information might influence further treatment decisions.

Hyperbaric oxygen therapy prevents subarachnoid hemorrhage-induced apoptosis and impaired contractility of the rabbit bladder.

AIM: To explore the effects of experimental subarachnoid hemorrhage (SAH) on rabbit urinary bladder and to assess the potential protective effects of hyperbaric oxygen therapy (HBOT). METHODS: A total of 15 male New Zealand white rabbits were divided randomly to one of three groups: group I was spared as the control group (n = 5), group II was exposed to SAH, received no treatment, and acted as the SAH group (n = 5) and group III was exposed to SAH and received five sessions of HBOT (started 12 hours after SAH induction and was given twice daily for the first 2 days and once on the third day) and acted as the treatment group (n = 5). At 72 hours after the SAH induction, bladders from all animals were removed for in vitro organ bath experiments and biochemical analyses. RESULTS: Isometric tension studies revealed that compared to group I, the contractile responses of the strips to carbachol in group II were significantly decreased whereas HBOT restored the contractile responses (P < .05). Caspase-3 and nitric oxide synthase (NOS) activities of bladder tissues were significantly increased in group II when compared with group I, whereas caspase-3 and NOS activities were significantly decreased in the tissues of group III (P < .01). CONCLUSIONS: Subarachnoid hemorrhage stimulates apoptosis of the rabbit bladder and impairs the contractile response of the rabbit bladder to carbachol. HBOT creates a protective effect in rabbit bladder tissues and restores SAH-induced changes.

Impact of the Charlson Comorbidity Index on dose-limiting toxicity and survival in locally advanced and metastatic renal cell carcinoma patients treated with first-line sunitinib or pazopanib.

BACKGROUND: Anti-angiogenic tyrosine kinase inhibitors, sunitinib and pazopanib, have proven efficacy in advanced renal cell carcinoma, with specific adverse events occurring during treatment process. Comorbidities can reflect functional status and have prognostic value in oncology patients. We aimed to assess the association of the Charlson Comorbidity Index with severe toxicities and mortality in renal cell carcinoma cases treated with front-line sunitinib or pazopanib. METHODS: Files of locally advanced and metastatic renal cell carcinoma patients who received first-line sunitinib or pazopanib were retrospectively examined. Charlson Comorbidity Index of each patient was calculated. Patients were also stratified into Memorial Sloan-Kettering Cancer Center risk groups. Predictors of dose-limiting toxicity were evaluated with binomial logistic regression analysis. Univariate and multivariate Cox regression models were utilized to determine prognostic factors for survival. RESULTS: The study included 102 patients, 64 were treated with first-line sunitinib and 38 with pazopanib. In 42 patients (41.9%), Charlson Comorbidity Index was 9 or more. Dose-limiting toxicities were significantly more frequent in Charlson Comorbidity Index ≥9 group (69% vs. 40%, p = 0.004), and Charlson Comorbidity Index independently predicted dose-limiting toxicity (Hazard ratio (HR) = 4.30, p = 0.002). After adjusting for other variables, a Charlson Comorbidity Index of ≥9 is also a significant prognostic factor for progression-free (HR = 1.76, p = 0.02) and overall survival (HR = 1.75, p = 0.03). CONCLUSIONS: Charlson Comorbidity Index may be a valuable method to estimate prognosis and optimize therapy in patients with advanced renal cell carcinoma receiving first-line sunitinib or pazopanib.

The Relationship Between Urothelial Type Bladder Cancer, Plasma 25-Hydroxyvitamin D Levels, and Vitamin D Receptor ApaI BsmI FokI, and TaqI Polymorphisms.

BACKGROUND: Bladder cancer is an important health problem which ranks 4th among most frequently seen cancer types in men. In our study we aimed to investigate the correlations among urothelial type bladder cancer polymorphisms, ApaI, BsmI, FokI, and TaqI, prevalently observed in the vitamin D receptor (VDR) gene and plasma vitamin D levels in a Turkish population. METHODS: Our study included 101 patients and 109 control subjects. Plasma 25(OH)D levels were determined using a HPLC method and VDR gene polymorphisms with PCR-RFLP method. RESULTS: A statistically significant intergroup difference was not observed with regard to age, gender, and BMIs of the patients. Median (min - max) 25(OH)D levels in the patient and the control groups were determined as 11.9 ng/dL (1.9 - 33.0 ng/dL) and 9.7 ng/dL (2.1 - 39.5 ng/dL), respectively. A statistically significant intergroup difference was not observed with regard to 25(OH)D levels (p = 0.402). A statistically significant intergroup differ-ence was not observed with regard to genotype distribution of ApaI, BsmI, and TaqI polymorphisms and allele frequencies. Control and urothelial type bladder cancer groups showed a statistically significant difference with respect to genotype distribution of FokI polymorphism (p = 0.048). However in a binary logistic regression model, when corrected OR values were estimated by including smoking history in the model, the correlation detected be-tween the presence of FF and increased risk of disease was not statistically significant (ORadj = 1.64, 95% CI = 0.89 - 3.02, p = 0.114). CONCLUSIONS: In the light of the data concerning Turkish population a statistically significant correlation could not be demonstrated between plasma vitamin D levels, ApaI, BsmI, FokI, and TaqI polymorphisms, and urothelial type bladder cancers. Since literature data are limited in number, further studies should be conducted in larger patient groups.

Functional roles and potential clinical application of miRNA-345-5p in prostate cancer.

BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNAs, which negatively regulate gene expression and impact prostate cancer (PCa) growth and progression. Circulating miRNAs are stable and detectable in cell-free body fluids, such as serum. Investigation of circulating miRNAs presents great potential in uncovering new insights into the roles of miRNAs in PCa diagnosis and therapy. METHODS: Using TaqMan miRNA quantitative reverse transcription polymerase chain reaction (RT-qPCR), we compared the expression levels of five miRNAs (miR-193a-3p, miR-9-3p, miR-335-5p, miR-330-3p, and miR-345-5p) in serum samples from 20 normal individuals without cancer, 25 patients with localized disease, 25 patients with hormone-naïve or hormone sensitive metastatic disease, and 25 patients with metastatic castration-resistant prostate cancer (CRPC). These five miRNAs were identified as potential oncogenes in our previous studies. MiR-345-5p was further investigated for its functional roles in CRPC cells. RESULTS: We discovered that miR-9-3p, miR-330-3p-3p, and miR-345-5p were significantly overexpressed in serum from PCa patients when compared to serum from individuals without cancer. No differential expression patterns were observed between different disease categories. However, patients who were in remission after androgen deprivation therapy (ADT) appeared to have significantly lower miR-345-5p levels compared to the rest of the groups. We further demonstrated that miR-345-5p promotes CRPC cell growth and migration in vitro and validated that CDKN1A (the gene encoding p21) is the direct target of miR-345-5p. CONCLUSIONS: Our results set the stage for a further investigation on the potential application of circulating miR-345-5p as a biomarker for PCa diagnosis and therapeutic response. The oncogenic roles of miR-345-5p through targeting CDKN1A render it a potential therapeutic target for PCa.

Pathologic Outcomes of Candidates for Active Surveillance Undergoing Radical Prostatectomy: Results from a Contemporary Turkish Patient Cohort.

INTRODUCTION: To evaluate the pathological outcomes of Turkish men meeting the criteria for Active Surveillance (AS), who elected to undergo immediate radical prostatectomy (RP). MATERIAL AND METHODS: Retrospective analysis including 1,212 patients with clinically localized prostate cancer (PCa) who met the eligibility criteria for AS. The primary outcomes were pathological upstaging and pathological upgrading. RESULTS: Nine hundred ninety-one patients were eligible for analysis after the central review of the submitted data. The mean prostate-specific antigen (PSA) level was 6.89 (0.51-15) ng/mL and the mean biopsy core number was 12 (8-47). The mean tumor positive core on final biopsy pathology was 1.95 (1-6) (16.6% [2.1-33.3%]). Overall, 30.6% of the men experienced a Gleason sum (GS) upgrade and 13.2% had pathological upstaging. For GS upgrade, the percentage of tumor-positive cores and free-to-total-PSA ratio were significant both in univariate analysis and multivariate logistic regression analysis. Variables predicting pathological upstaging were percentage of tumor-positive cores and PSA density, which were significant in univariate analysis. However, only PSA density was significant in multivariate logistic regression. Although biochemical recurrence-free survival was longer in patients without GS upgrade, it was not statistically significant between patients with and without any GS upgrade (mean 133.7 vs. 148.2 months, p = 0.243). A similar observation was made for patients with or without pathological upstaging (mean 117.1 vs. 148.3 months, p = 0.190). CONCLUSIONS: Upgrading and upstaging at RP are quite common among Turkish men with clinically low-risk PCa, who are candidates for AS, and a great majority of them experienced long-term PSA control.

Androgen receptor-regulated miRNA-193a-3p targets AJUBA to promote prostate cancer cell migration.

Background Dysregulation of microRNA (miRNA) expression is implicated in cancer development and progression by modulating oncogenes or tumor suppressors at the post-transcriptional level. Methods To investigate the role of miRNAs in prostate cancer (PCa) progression, we performed small RNA-sequencing (RNA-seq) analysis in androgen-dependent LNCaP cells and LNCaP-derived castration-resistant prostate cancer (CRPC) C4-2B cells. For functional validation, we specifically investigated miR-193a-3p, which is highly upregulated in C4-2B cells and modulated by the androgen receptor (AR). We elucidated the role of miR-193a-3p and its downstream target gene in PCa cell migration using biochemical approaches. Results We identified a subset of differentially expressed miRNAs in C4-2B cells compared to LNCaP cells. Computational analysis shows that the targets of upregulated miRNAs are significantly associated with downregulated protein-coding mRNAs in C4-2B cells. Gene Ontology analysis further reveals that these downregulated mRNAs are significantly enriched in cell-cell adhesion functions. Downregulation of these miRNA-targeted genes may change PCa cell motility resulting in the acquisition of metastatic potential. We then focus on miR-193a-3p and demonstrate overexpression of miR-193a-3p increases cell migration through downregulating its target AJUBA. AJUBA is a LIM domain protein and contributes to the formation and stability of cadherin-mediated cell-cell adhesion. Loss of AJUBA enhances PCa migration and downregulation of AJUBA expression is observed in metastatic PCa tumors. Conclusions Our results suggest a novel AR/miR-193a-3p/AJUBA pathway implicated in PCa progression. MiR-193a-3p is a potential therapeutic target for metastatic PCa.

The effect of doxazosin and sildenafil citrate combination on bladder tissue contractility, alpha adrenergic receptor, and iNOS subtype expression in a male rat model of partially bladder outlet obstruction.

AIMS: Our aim was to investigate the effects of doxazosin, sildenafil, and their combination on bladder tissue contractility and adrenergic receptor (AR) and inducible nitric oxide synthase (iNOS) expression utilizing a male rat model of partial urethral obstruction (PUO). METHODS: Thirty male Sprague Dawley rats were divided into five groups. Except the SHAM group, all animals in remaining four groups underwent surgery for PUO. No further treatment was given to the first group (NT group). Remaining three groups received 6 weeks of treatment with 20 mg/kg doxazosin (D group), 20 mg/kg sildenafil (S group), 20 mg/kg doxazosin, and 20 mg/kg sildenafil combination (DS group), respectively via oral gavage. Then, bladder strips were harvested from each animal for isometric tension studies and for real time polymerase chain reaction studies of both AR subtypes and iNOS mRNA. RESULTS: Contractile responses to carbachol and electrical field stimulation at various concentrations/frequencies showed a significant increase after PUO. Any treatment helped to normalize these increased responses. Alpha 1a and 1d AR subtype expressions were found to be down- and up-regulated, respectively, in every group with PUO, compared to SHAM group. iNOS expression was similar in D and NT groups and significantly increased in S and DS groups. CONCLUSIONS: Contractile changes of rat bladder tissue due to PUO were prevented by sildenafil or doxazosin alone or in combination where combination treatment did not provide any additional advantage. Further studies are needed to clarify the role of phosphodiesterase inhibitors and combination treatment in the treatment of LUTS.

Is 40 cm H2 O detrusor leak point pressure cut-off reliable for upper urinary tract protection in children with myelodysplasia?

PURPOSE: The purpose of this study, is to find out the most accurate cut-off level for the detrusor leak point pressure (DLPP) in terms of upper urinary tract (UUT) protection in a cohort of children with myelodysplasia. MATERIALS AND METHODS: One hundred and ninety-three children with myelodysplasia were included in the study based on the availability of urological evaluation at age of 3 years. Children were assigned to one of two groups-those who had UUT damage at age 3 (group 1, n: 70) and those without UUT changes (group 2, n: 123), and compared. RESULTS: Urological follow-up data revealed higher incidences of febrile urinary tract infections and secondary tethering of the spinal cord in group 1. No statistically significant difference was determined between group 1 and group 2 in terms of DLPP values (median 42.5 vs. 39.5 cm H2 O, respectively, P = 0.087). Analysis of different cut-off values showed that DLPP above 20 cm H2 O had a higher sensitivity for UUT damage (91.4%). A normal UUT was found in 56.5% and 62.2% of children with DLPP between 20 and 40 cm H2 O, and with DLPP over 40 cm H2 O, respectively. CONCLUSIONS: Present study showed that more than half of the children with myelodysplasia had normal UUT function even with a DLPP of 40 cm H2 O and over. Thus, DLPP, is not the sole decision making parameter to rely for more invasive therapies in children with myelodysplasia. On the other hand, a DLPP cut-off value of 20 cm H2 O showed a higher sensitivity to predict UUT damage instead of 40 cm H2 O. Neurourol. Urodynam. 36:759-763, 2017. © 2016 Wiley Periodicals, Inc.

The effect of intradetrusor botulinum neurotoxin type A on urinary NGF, TGF BETA-1, TIMP-2 levels in children with neurogenic detrusor overactivity due to myelodysplasia.

AIMS: The aim of this study was to determine the value of urine nerve growth factor (NGF), transforming growth factor beta 1 (TGF-Beta-1), tissue inhibitor of matrix metalloproteinase 2 (TIMP-2) levels to predict the urodynamic profile before and after botulinum neurotoxin type A (BoNT-A) treatment in children with myelodysplasia. METHODS: This prospective study included 15 children with myelodysplasia who underwent intradetrusor BoNT-A injections due to neurogenic detrusor overactivity (NDOA). Urine samples of each child were collected before and after BoNT-A injections, specifically at the first and third postoperative months. Urine samples were analyzed with ELISA method and NGF, TGF-Beta-1, and TIMP-2 levels were measured. Urine marker levels and clinical findings were assessed for statistical significance with Wilcoxon Signed Ranks Test and Friedman Test. RESULTS: A total of 15 children (5 boys and 10 girls) were assigned as the study group. Mean age of the patients was 7.1 ± 2.5 years (range 2.5-11). A statistically significantly decline was observed in urinary TGF-Beta-1 and NGF levels following BoNT-A injections, compared to the preoperative levels (P < 0.05). TIMP-2 levels also tend to decrease following BoNT-A injections but this was not statistically significant compared to the preoperative levels. CONCLUSION: This preliminary study, suggests urinary TGF-Beta-1 and NGF as a potent marker in children with NDOA, as they decline following BoNT-A injection. Further studies are needed in identifying their special role in assessing treatment success after invasive interventions.

The Contemporary Incidence and Sequelae of Rhabdomyolysis Following Extirpative Renal Surgery: A Population Based Analysis.

PURPOSE: We evaluate the contemporary incidence and consequences of postoperative rhabdomyolysis after extirpative renal surgery. MATERIALS AND METHODS: We conducted a population based, retrospective cohort study of patients who underwent extirpative renal surgery with a diagnosis of a renal mass or renal cell carcinoma in the United States between 2004 and 2013. Regression analysis was performed to evaluate 90-day mortality (Clavien grade V), nonfatal major complications (Clavien grade III-IV), hospital readmission rates, direct costs and length of stay. RESULTS: The final weighted cohort included 310,880 open, 174,283 laparoscopic and 69,880 robotic extirpative renal surgery cases during the 10-year study period, with 745 (0.001%) experiencing postoperative rhabdomyolysis. The presence of postoperative rhabdomyolysis led to a significantly higher incidence of 90-day nonfatal major complications (34.7% vs 7.3%, p <0.05) and higher 90-day mortality (4.4% vs 1.02%, p <0.05). Length of stay was twice as long for patients with postoperative rhabdomyolysis (incidence risk ratio 1.83, 95% CI 1.56-2.15, p <0.001). The robotic approach was associated with a higher likelihood of postoperative rhabdomyolysis (vs laparoscopic approach, OR 2.43, p <0.05). Adjusted 90-day median direct hospital costs were USD 7,515 higher for patients with postoperative rhabdomyolysis (p <0.001). Our model revealed that the combination of obesity and prolonged surgery (more than 5 hours) was associated with a higher likelihood of postoperative rhabdomyolysis developing. CONCLUSIONS: Our study confirms that postoperative rhabdomyolysis is an uncommon complication among patients undergoing extirpative renal surgery, but has a potentially detrimental impact on surgical morbidity, mortality and costs. Male gender, comorbidities, obesity, prolonged surgery (more than 5 hours) and a robotic approach appear to place patients at higher risk for postoperative rhabdomyolysis.

Trends in utilisation, perioperative outcomes, and costs of nephroureterectomies in the management of upper tract urothelial carcinoma: a 10-year population-based analysis.

OBJECTIVE: To perform a population-based study to evaluate contemporary utilisation trends, morbidity, and costs associated with nephroureterectomies (NUs), as contemporary data for NUs are largely derived from single academic institution series describing the experience of high-volume surgeons and it is unclear if the same favourable results occur at a national level. PATIENTS AND METHODS: Using the Premier Hospital Database, we captured patients undergoing a NU with diagnoses of renal pelvis or ureteric neoplasms from 2004 to 2013. We fitted regression models, adjusting for clustering by hospitals and survey weighting to evaluate 90-day postoperative complications, operating-room time (OT), prolonged length of stay (pLOS), and direct hospital costs among open (ONU), laparoscopic (LNU) and robotic (RNU) approaches. RESULTS: After applying sampling and propensity weights, we derived a final study cohort of 17 254 ONUs, 13 317 LNUs and 3774 RNUs for upper tract urothelial carcinoma (UTUC) in the USA between 2004 and 2013. During that period, minimally invasive NU (miNU) increased from 36% to 54%, while the total number of NUs decreased by nearly 20%. No differences were noted in perioperative outcomes between the three surgical approaches, including when the analysis was restricted to the highest-volume hospitals and highest-volume surgeons. The OT was longer for LNU and RNU (P < 0.001), while the pLOS rates were decreased (P < 0.001). Adjusted 90-day median direct hospital costs were higher for LNU and RNU (P < 0.001), which disappeared when adjusting for the highest-volume groups, except for RNUs performed by high-volume surgeons. CONCLUSIONS: During this contemporary 10-year study, miNU has been replacing ONU for UTUC with a recent surge in RNU, along with a concurrent reduction in total NUs performed. Despite not being associated with a clinically significant improvement in perioperative outcomes, the costs for miNUs were consistently higher. However, higher hospital volumes suggest a potential cost containment strategy when performing miNUs.

Significance of the interval between first and second transurethral resection on recurrence and progression rates in patients with high-risk non-muscle-invasive bladder cancer treated with maintenance intravesical Bacillus Calmette-Guérin.

OBJECTIVES: To evaluate the effect of the interval between the initial and second transurethral resection (TUR) on the outcome of patients with high-risk non-muscle-invasive bladder cancer (NMIBC) treated with maintenance intravesical Bacillus Calmette-Guérin (BCG) therapy. PATIENTS AND METHODS: We reviewed the data of patients from 10 centres treated for high-risk NMIBC between 2005 and 2012. Patients without a diagnosis of muscle-invasive cancer on second TUR performed ≤90 days after a complete first TUR, and received at least 1 year of maintenance BCG were included in this study. The interval between first and second TUR in addition to other parameters were recorded. Multivariate logistic regression analysis was used to identify predictors of recurrence and progression. RESULTS: In all, 242 patients were included. The mean (sd, range) follow-up was 29.4 (22.2, 12-96) months. The 3-year recurrence- and progression-free survival rates of patients who underwent second TUR between 14 and 42 days and 43-90 days were 73.6% vs 46.2% (P < 0.001) and 89.1% vs 79.1% (P = 0.006), respectively. On multivariate analysis, the interval to second TUR was found to be a predictor of both recurrence [odds ratio (OR) 3.598, 95% confidence interval (CI) 1.885-8.137; P = 0.001] and progression (OR 2.144, 95% CI 1.447-5.137; P = 0.003). CONCLUSIONS: The interval between first and second TUR should be ≤42 days in order to attain lower recurrence and progression rates. To our knowledge, this is the first study demonstrating the effect of the interval between first and second TUR on patient outcomes.

Diagnostic value of the pediatric lower urinary tract symptom score in children with overactive bladder.

PURPOSE: The aims were (1) to assess the pediatric lower urinary tract symptom score (SS) prior to treatment as a means of determining severity of overactive bladder (OAB) and (2) to investigate relationships between SS results and those of standard diagnostic modalities. MATERIALS AND METHODS: Symptom scores were recorded pre- and 6 months SS for 294 children with OAB unrelated to neurological disorder. Uroflowmetry-electromyography data, total bladder capacity, and a 2-day bladder diary were also recorded, and upper urinary tract deterioration was investigated as indicated. Overactive bladder was treated with standard approaches. No response to treatment was defined as 0-49% reduction in OAB-related symptoms based on SS results. Non-responders underwent additional evaluations as indicated. RESULTS: Two hundred forty-one patients (97%; mean age 9.8 ± 2.8 years; mean follow-up 11 months; range 6-18 months) completed the study. One hundred thirteen (47%) required ultrasonography (USG), and those with abnormal USG had a significantly higher pre- and 6 months SS (p = 0.016). All non-responders (n = 38; 16%) underwent urodynamics evaluation, 34 underwent spinal magnetic resonance imaging (MRI), 34 underwent voiding cystourethrography (VCUG), and 34 underwent dimercaptosuccinic acid scanning (DMSA). Non-responders with terminal detrusor hyperactivity had significantly lower SS after therapy (p = 0.09). Non-responders with abnormal MRI had higher pre- and 6 months SS than those with normal MRI. Thirteen (38%) of the non-responders who required VCUG had vesicoureteral reflux (VUR), and this subgroup had higher pre-treatment SS (p = 0.030). Seven (21%) of the non-responders who required DMSA had scarring, and all 7 had VUR. The subgroup with scarring had higher pre-treatment SS (p = 0.030). CONCLUSION: Pediatric OAB patients with high 6 months SS have a higher incidence of additional upper urinary tract pathology. Those with low pre-treatment SS require fewer laboratory tests and other assessments. The SS tool can reduce the number of urodynamics evaluations, and other tests required to diagnose renal damage in children with OAB.

Melatonin and tadalafil treatment improves erectile dysfunction after spinal cord injury in rats.

Oxidative stress plays an important role both in spinal cord injury (SCI) and erectile dysfunction (ED). The present study investigated the effects of melatonin and tadalafil treatment alone or in combination on SCI-induced ED. Male Wistar albino rats (n = 40) were divided into five groups: sham-operated control and SCI-injured rats given either vehicle, melatonin (10 mg/kg, i.p.), tadalafil (10 mg/kg, p.o.) or a combination of melatonin and tadalafil. Spinal cord injury was induced using a standard weight-drop method. On Day 7 after SCI, intracavernosal pressure (ICP) was measured and all rats were decapitated. Cavernosal tissues were obtained to examine caspase 3, nitric oxide synthase (NOS), myeloperoxidase (MPO) and superoxide dismutase (SOD) activities, as well as cGMP, nerve growth factor (NGF), malondialdehyde (MDA) and glutathione (GSH) levels. Spinal cord injury caused oxidative damage, as evidenced by increases in MDA and cGMP levels. In addition, MPO and caspase 3 activites were increased after SCI, whereas GSH and NGF levels and SOD activity were reduced. Melatonin effectively reversed these oxidative changes. Furthermore, in rats treated with both melatonin and tadalafil, the recoveries were more pronounced than in rats given either melatonin or tadalafil alone. The ICP/mean arterial pressure value in vehicle-treated SCI rats was significantly higher than in the control group, whereas in the tadalafil- and tadalafil + melatonin-treated groups have returned this value had returned to control levels. As an individual treatment, and especially when combined with tadalafil, a well-known agent in the treatment of ED, melatonin prevented SCI-induced oxidative damage to cavernosal tissues and restored ED, most likely due to its anti-oxidant effects.

Artificial intelligence assisted patient blood and urine droplet pattern analysis for non-invasive and accurate diagnosis of bladder cancer.

Bladder cancer is one of the most common cancer types in the urinary system. Yet, current bladder cancer diagnosis and follow-up techniques are time-consuming, expensive, and invasive. In the clinical practice, the gold standard for diagnosis remains invasive biopsy followed by histopathological analysis. In recent years, costly diagnostic tests involving the use of bladder cancer biomarkers have been developed, however these tests have high false-positive and false-negative rates limiting their reliability. Hence, there is an urgent need for the development of cost-effective, and non-invasive novel diagnosis methods. To address this gap, here we propose a quick, cheap, and reliable diagnostic method. Our approach relies on an artificial intelligence (AI) model to analyze droplet patterns of blood and urine samples obtained from patients and comparing them to cancer-free control subjects. The AI-assisted model in this study uses a deep neural network, a ResNet network, pre-trained on ImageNet datasets. Recognition and classification of complex patterns formed by dried urine or blood droplets under different conditions resulted in cancer diagnosis with a high specificity and sensitivity. Our approach can be systematically applied across droplets, enabling comparisons to reveal shared spatial behaviors and underlying morphological patterns. Our results support the fact that AI-based models have a great potential for non-invasive and accurate diagnosis of malignancies, including bladder cancer.

Oncological Outcomes of Chromophobe Versus Clear Cell Renal Cell Carcinoma: Results from A Contemporary Turkish Patient Cohort.

PURPOSE: To compare the oncological outcomes of clear cell RCC (ccRCC), which is common in renal cell carcinomas (RCC), and chromophobic RCC (chRCC), which is less common, and to define the factors affecting survival in the Turkish patient population for both RCC subclassifications. MATERIALS AND METHODS: Patients with a pathologically confirmed RCC diagnosis after radical or partial nephrectomy in the Turkish Urooncology Association (TUOA), Urological Cancers Database-Kidney (UroCaD-K), were retrospectively reviewed. Patients with ccRCC and chRCC were included in the study. Primary outcomes of this study are recurrence-free survival (RFS), overall survival (OS) and cancer-specific survival (CSS) for each histological subtype. RESULTS: Data from 5300 patients in the TUOA UroCaD-K are reviewed and a total of 2560 patients (2225 in the ccRCC group and 335 in the chRCC group) are included in the final analysis. In the comparison of the groups, tumor size was greater both radiologically and pathologically in chRCC (p=0.019 vs 0.002 respectively). Recurrence-free survival (RFS), overall survival (OS) and cancer-specific survival (CSS) rates are worse in ccRCC subgroup. In the evaluation of risk factors; pathological stage, local invasion and Fuhrmann grade were found to be significant for recurrence in ccRCC. Age, body mass index and pathological stage were the risk factors affecting overall mortality (OM). Pathological tumor size was an independent risk factor for recurrence in chRCC, while age was analyzed as the only parameter affecting OM. CONCLUSION: chRCC oncological data and OS, CSS and RFS rates were found to be better than ccRCC in the Turkish patient population.

Beneficial effects of quercetin on rat urinary bladder after spinal cord injury.

BACKGROUND: Spinal cord injury (SCI) leads to an inflammatory response and generates oxidative stress, which has deleterious effects on the function of several organ systems, including the urinary bladder. The present study was designed to investigate the putative beneficial effect of quercetin against SCI-induced bladder damage. MATERIALS AND METHODS: In order to induce SCI, a standard weight-drop method that induced a moderately severe injury (100 g/cm force) at T10 was used. Injured animals were given either 20 mg/kg quercetin or vehicle 15 min post injury and repeated twice daily for 7 d. After decapitation, bladder strips were placed in organ bath and isometric contractions to carbachol (10(-8) to10(-4) M) were recorded. In order to examine oxidative tissue injury, luminol chemiluminescence, nitric oxide, malondialdehyde, and glutathione levels and superoxide dismutase, myeloperoxidase, and caspase 3 activities of bladder tissues were measured along with histologic evaluations. Proinflammatory cytokines tumor necrosis factor α, interleukin 1ß, and interleukin 6 were also assayed in blood samples. RESULTS: In the injured animals, the contractile responses of the bladder strips were lower than those of the control group and were reversed by treatment with quercetin. On the other hand, increase in nitric oxide, malondialdehyde, luminol chemiluminescence levels, and myeloperoxidase and caspase 3 activities of tissues in the SCI group were significantly reversed by quercetin treatment. Similarly, plasma cytokine levels, which were elevated in the vehicle-treated SCI group, were reduced with quercetin treatment. Furthermore, treatment with quercetin also prevented the depletion of tissue glutathione levels and superoxide dismutase activity seen in the SCI group. CONCLUSIONS: According to the results, quercetin exerts beneficial effects against SCI-induced oxidative damage through its anti-inflammatory and antioxidant effects.