Human Wharton's jelly-derived mesenchymal stromal stem cells preconditioned with valproic acid promote cell migration and reduce renal inflammation in ischemia/reperfusion injury by activating the AKT/P13K and SDF1/CXCR4 pathways.

OBJECTIVE: To determine whether WJ-MSCs pretreated with VPA would enhance their migration to improve functional recovery of renal IRI in rats. METHODS: 150 Sprague-Dawley rats were distributed into 5 groups; Sham, IRI, WJ-MSC, VPA, and WJ-MSCs + VPA. 10 rats were sacrificed after 3, 5, and 7 days. Role of WJ-MSCs pretreated with VPA was evaluated by assessment of renal function, antioxidant enzymes together with renal histopathological and immunohistopathological analyses and finally by molecular studies. RESULTS: WJ-MSCs and VPA significantly improved renal function and increased antioxidants compared to IRI group. Regarding gene expression, WJ-MSCs and VPA decreased BAX and TGF-ß1, up-regulated Akt, PI3K, BCL2, SDF1α, and CXCR4 related to IRI. Additionally, WJ-MSCs pretreated with VPA improved the measured parameters more than either treatment alone. CONCLUSION: WJ-MSCs isolated from the umbilical cord and pretreated with VPA defended the kidney against IRI by more easily homing to the site of injury.

Association between hepatitis C virus genotype 4 and renal cell carcinoma: Molecular and virological studies.

Hepatitis C virus (HCV) is the most common infection worldwide. The correlation between HCV and renal cell carcinoma (RCC) is still mysterious. Therefore, the relationship between HCV and RCC was investigated. The study included 100 patients with RCC; 32 with HCV infection, and 68 without HCV infection. Expressions of viral proteins (NS3 and NS5A) were tested using an immune electron-microscope (IEM) and immunohistochemistry (IHC). IHC and quantitative real time-PCR investigated the presentation of human proteins TP53 and p21 genes. Transmission electron (TEM) detected viral-like particles in infected RCC tissues. The gene and protein expression of P53 was higher in HCV positive versus HCV negative patients and p21 was lower in HCV positive versus HCV negative in both tumor and normal tissue samples. Viral like particles were observed by TEM in the infected tumor and normal portion of the RCC tissues and the plasma samples. The IEM showed the depositions of NS3 and NS5A in infected renal tissues, while in noninfected samples, were not observed. The study hypothesizes that a correlation between HCV and RCC could exist through successfully detecting HCV-like particles, HCV proteins, and (p53 and p21) in RCC-infected patients.

Predictive value of immunological markers after bacille Calmette-Guérin induction in bladder cancer.

OBJECTIVES: To investigate the predictive value of different immunological markers on treatment outcomes after bacille Calmette-Guérin (BCG) induction in high-risk non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: Patients who underwent transurethral resection of bladder tumour for NMIBC were assessed for study eligibility. Urine and blood samples were taken from patients at baseline (immediately before first dose of induction) and after induction (4 h after last [sixth] dose). Urine samples were evaluated for interleukin (IL)-2 and IL-10 by solid-phase enzyme-linked immunosorbent assay. Blood samples were evaluated for tumour necrosis factor α (TNF-α), cytotoxic T-lymphocyte antigen 4 (CTLA-4) and transcription factors (TFs) (GATA-binding protein 3 [GATA3], T-box expressed in T cells [T-bet], and forkhead box protein 3 [FoxP3]) using quantitative reverse transcriptase-polymerase chain reaction analysis. Change pattern and fold change of each evaluable marker was assessed in relation to different treatment outcomes (initial complete response [ICR]/recurrence/progression). RESULTS: Between July 2013 and May 2019, 204 patients were included. Among evaluable markers, urinary IL-2 and serum TNF-α increased in all patients, serum CTLA-4 and FoxP3+ showed a predominant decreased pattern in 188 (92.2%) and 192 (94.1%) patients, respectively. An ICR was achieved in 186 (91.2%) patients. Serum TNF-α fold change and urinary IL-10 change pattern were significantly associated with an ICR (P = 0.001 and P = 0.03, respectively). At a median (range) follow-up of 37 (20-88) months, 104 (56%) patients developed recurrence. Urinary IL-10, serum CTLA-4, T-bet+ , FoxP3+ change patterns and GATA3+ /T-bet+ ratio were significantly associated with tumour recurrence (P = 0.001, P = 0.001, P = 0.02, P = 0.009 and P = 0.001, respectively). Tumour progression occurred in 34 (18.3%) patients. Urinary IL-10, serum CTLA-4, serum T-bet+ change patterns and GATA3+ /T-bet+ ratio were independent predictors of tumour progression (P = 0.001, P = 0.001, P = 0.02 and P = 0.001, respectively). CONCLUSIONS: Urinary IL-10 and serum TNF-α can significantly predict ICR. Moreover, change pattern of urinary IL-10, serum CTLA-4, TFs (GATA3, T-bet and FoxP3) and GATA3+ /T-bet+ ratio after BCG induction can independently predict further BCG response. These markers could be implemented in clinical practice when management options are discussed or in systems with severe BCG shortage.

Omega-3 polyunsaturated fatty acids: a modified approach for chemo-prevention of bladder cancer in a rat model and molecular studies of antineoplastic mechanisms.

OBJECTIVES: To test the chemo-preventative effects of omega-3 against bladder cancer (BC) induction in a rat model and its potential antineoplastic mechanisms. MATERIAL AND METHODS: Ninety male Fisher rats were divided into three groups during a 22-week protocol: group 1 (control), group 2 (Placebo + N-butyl-N-4- hydroxybutyl nitrosamine (BBN) for induction of BC and group 3 received omega-3 (1200 mg/kg/day) + BBN. At the end, blood samples and bladder tissues were collected and checked for the presence of malignancy, markers of angiogenesis (VEGF relative gene expression), inflammation (IL-6), proliferation (KI-67 expressions), oxidative stress (serum MDA and serum SOD) and epigenetic control (miRNA-145 level). RESULTS: At the end of the study, 60% and 86.6% rats survived in group 2 and 3 with significant weight loss among rats in group 2 when compared with other groups. In group 2, all rats developed visible bladder lesions of which five and 13 developed squamous cell carcinoma (SCC) and transitional cell carcinoma (TCC). In omega3-treated group, only one developed low grade SCC and one developed high grade non- invasive TCC. Bladders from omega-3-treated rats showed lower expression ofKI-67 (p < 0.05), VEGF (p < 0.001) and IL-6 (p < 0.001) and significant higher expression of mi-RNA (p < 0.001). Also, omega-3-treated group showed statistically significant lower MDA level (p < 0.001). CONCLUSION: Omega-3 inhibits bladder tumor growth in the BBN-induced BC rat model, due to anti-inflammatory, antioxidant, anti-proliferative, and anti-angiogenic properties together with epigenetic control.

Mirabegron for treatment of erectile dysfunction concomitant with lower urinary tract symptoms in patients with benign prostatic obstruction: A randomized controlled trial.

OBJECTIVE: To assess the efficacy of mirabegron in the treatment of erectile dysfunction concomitant with lower urinary tract symptoms in benign prostatic obstruction patients. METHODS: In this randomized controlled trial, 55 sexually active lower urinary tract symptoms/benign prostatic obstruction patients with concomitant erectile dysfunction were randomly allocated in two groups: the first received mirabegron 50 mg plus doxazosin 2 mg once daily (mirabegron group) and the second received tolterodine 4 mg plus doxazosin 2 mg (tolterodine group) for 12 weeks. The evaluation was based on the International Index of Erectile Function questionnaire, Erection Hardness Score questionnaire, International Prostate Symptom Score, quality of life, uroflowmetry and post-voiding residual. The therapeutic outcomes were assessed at 4 and 12 weeks compared with the baseline. RESULTS: Only the mirabegron group achieved significant improvement in sexual functions after 4 and 12 weeks. By using ≥5 points difference from the baseline as a cut-off point of change, there was a significant difference in change of direction of the International Index of Erectile Function-15 total score in favor of the mirabegron group; after 12 weeks, the International Index of Erectile Function-15 total score decreased in 0%, was unchanged in 8.3% and improved in 91.7% in the mirabegron group compared with 8.7%, 65.2% and 26.1%, respectively, in the tolterodine group (P < 0.001). Regarding the urinary characteristics, both groups showed significant improvement in the International Prostate Symptom Score, quality of life, and post-voiding residual after 4 and 12 weeks, with no significant difference among them. CONCLUSION: Mirabegron improves urinary characteristics and the associated sexual dysfunction in patients with lower urinary tract symptoms/benign prostatic obstruction.

Effect of low-energy shock wave therapy on intravesical epirubicin delivery in a rat model of bladder cancer.

OBJECTIVES: To study the efficacy of low-energy shock wave therapy (LESW) on enhancing intravesical epirubicin (EPI) delivery in a rat model of bladder cancer (BCa). MATERIALS AND METHODS: A total of 100 female Fischer rats were randomly allocated into five groups: control; BCa; LESW; EPI; and EPI plus LESW. After BCa induction by N-butyl-N-(4-hydroxybutyl)nitrosamine, EPI (0.6 mg/0.3 mL of EPI diluted in 0.3 mL saline) or saline (0.6 mL) was administered and retained in the bladders for 1 h with or without LESW treatment (300 pulses at 0.12 mJ/mm2 ). This was repeated weekly for 6 weeks. Survival was then calculated, rats were weighed and their bladders were harvested for bladder/body ratio estimation, histopathological examination, p53 immunostaining, miR-210, hypoxia-inducible factor (HIF)-1α, tumour necrosis factor (TNF)-α and interleukin (IL)-6 relative gene expression and fluorescence spectrophotometric drug quantification. Heart and blood samples were also collected for assessment of the safety profile and toxicity. RESULTS: The EPI plus LESW group had significantly lower mortality rates, loss of body weight and bladder/body ratio. Histopathological results in terms of grossly visible bladder lesions, mucosal thickness, dysplasia formation and tumour invasion were significantly better in the combined treatment group. The EPI plus LESW group also had statistically significant lower expression levels of p53 , miR-210, HIF-1α, TNF-α and IL-6. LESW increased urothelial concentration of EPI by 5.7-fold (P < 0.001). No laboratory variable exceeded the reference ranges in any of the groups. There was an improvement of the indicators of EPI-induced cardiomyopathy in terms of congestion, hyalinization and microvesicular steatosis of cardiomyocytes (P = 0.068, 0.003 and 0.046, respectively) in the EPI plus LESW group. CONCLUSIONS: The combined use of intravesical EPI and LESW results in less BCa invasion and less dysplasia formation, as LESW increases urothelial permeability of EPI and enhances its delivery into tumour tissues, without subsequent toxicity.

Effect of losartan on the recoverability of renal function in anuric and oliguric patients with a solitary obstructed kidney: a double-blind randomized placebo-controlled trial.

OBJECTIVES: To assess the role of the angiotensin receptor blocker losartan on the recoverability of renal function after de-obstruction in patients with anuria and oliguria. MATERIALS AND METHODS: This was a double-blind randomized placebo-controlled trial in anuric or oliguric patients with calcular obstruction of solitary kidney. Patients with an anomalous kidney or those with an American Society of Anesthesiology score of >3 were excluded. After relief of obstruction, patients were allocated to receive either losartan potassium 25 mg or placebo for 3 months. Serum creatinine (sCr) and renographic glomerular filtration rate (GFR) were measured at nadir and after 3 months. Changes in sCr and renographic GFR were calculated by subtracting the values at nadir from those at 3 months. Improvement, stabilization or deterioration of sCr and renographic GFR were defined as percentage increase or decrease from nadir ≥10%, while changes <10% were considered as stabilization. RESULTS: A total of 76 patients completed 3 months of follow-up. Demographics and peri-operative data were comparable in the two groups. The median (range) sCr change was -1.05 (-1.8, 0.4) and -0.5 (-1.3, 0.1) mg/dL in the losartan and placebo, groups, respectively (P = 0.07). In the losartan group, renographic GFR had improved in 26 (59.1%) and deteriorated in six (13.6%) patients, while, in the placebo group, it had improved in eight (25%) and deteriorated in 10 patients (31.3%; P = 0.01). Losartan also enhanced renographic GFR improvement vs placebo by a median (range) of 6.9 (-9, 44) vs 1.4 (-10, 32) mL/min (P = 0.004). CONCLUSIONS: In patients with anuria and oliguria, losartan treatment contributes to renal function recoverability after relief of calcular obstruction of the solitary kidney.

A randomized trial comparing bipolar transurethral vaporization of the prostate with GreenLight laser (xps-180watt) photoselective vaporization of the prostate for treatment of small to moderate benign prostatic obstruction: outcomes after 2 years.

OBJECTIVE: To test the non-inferiority of bipolar transurethral vaporization of the prostate (TUVP) compared to GreenLight laser (GL) photoselective vaporization of the prostate (PVP) for reduction of benign prostatic hyperplasia-related lower urinary tract symptoms in a randomized trial. METHODS: Eligible patients with prostate volumes of 30-80 mL were randomly allocated to GL-PVP (n = 58) or bipolar TUVP (n = 61). Non-inferiority of symptom score (International Prostate Symptom Score [IPSS]) at 24 months was evaluated. All peri-operative variables were recorded and compared. Urinary (IPSS, maximum urinary flow rate and post-void residual urine volume) and sexual (International Index of Erectile Function-15) outcome measures were evaluated at 1, 4, 12 and 24 months. Need for retreatment and complications, change in PSA level and health resources-related costs of both procedures were recorded and compared. RESULTS: Baseline and peri-operative variables were similar in the two groups. At 1, 4, 12 and 24 months, 117, 116, 99 and 96 patients, respectively, were evaluable. Regarding urinary outcome measures, there was no significant difference between the groups. The mean ± sd IPSS at 1 and 2 years was 7.1 ± 3 and 7.9 ± 2.9 (P = 0.8), respectively, after GL-PVP and 6.3 ± 3.1 and 7.2 ± 2.8, respectively, after bipolar TUVP (P = 0.31). At 24 months, the mean difference in IPSS was 0.7 (95% confidence interval -0.6 to 2.3; P = 0.6). The median (range) postoperative PSA reduction was 64.7 (25-99)% and 65.9 (50-99)% (P = 0.006) after GL-PVP, and 32.1 (28.6-89.7)% and 39.3 (68.8-90.5)% (P = 0.005) after bipolar TUVP, at 1 and 2 years, respectively. After 2 years, retreatment for recurrent bladder outlet obstruction was reported in eight (13.8%) and 10 (16.4%) patients in the GL-PVP and bipolar TUVP groups, respectively (P = 0.8). The mean estimated cost per bipolar TUVP procedure was significantly lower than per GL-PVP procedure after 24 months (P = 0.01). CONCLUSIONS: In terms of symptom control, bipolar TUVP was not inferior to GL-PVP at 2 years. Durability of the outcome needs to be tracked. The greater cost of GL-PVP compared with bipolar TUVP is an important concern.

Optimal non-invasive treatment of 1-2.5 cm radiolucent renal stones: oral dissolution therapy, shock wave lithotripsy or combined treatment-a randomized controlled trial.

PURPOSE: To evaluate the efficacy of oral dissolution therapy (ODT), shock wave lithotripsy (SWL), and combined SWL and ODT for medium-sized radiolucent renal stone (RLS). METHODS: A randomized controlled trial for patients with medium-sized RLS, 1-2.5 cm, ≤ 500 Hounsfield unit (HU). The ODT patients were counseled for oral potassiumsodium-hydrogen citrate (Uralyt-U®). The 2nd group underwent SWL and the last group had combined SWL and ODT. The primary outcome, stone-free rate (SFR) at 3 months, was assessed by non-contrast computed tomography (NCCT). We defined complete response (success) if no residual fragment were detected by NCCT; partial response (failure) if there was a decrease in stone size, but presence of residual stones; no response if there was no change or increase in stone size (failure). RESULTS: 150 patients completed follow-up. The SFR at 1st month and 3rd month were, respectively; 16% and 50% in the ODT group, 10% and 46% in the SWL group, and 35% and 72% patients in combined group with (p = 0.03 and 0.003, respectively. The overall SFR for all groups was 66%. Combined treatment and initial response in first month follow-up were independent factors predicting SFR. In addition, combined treatment significantly decreased the overall stone volume (p = 0.03) and the need for additional stone management procedures after 3 months (p = 0.01). CONCLUSION: Combined ODT and SWL treatment constitutes the most rapid and effective therapeutic approach for medium-sized RLS, decreasing overall stone volume as well as the number of SWL sessions needed in comparison to SWL therapy, alone.

Low energy shock wave-delivered intravesical botulinum neurotoxin-A potentiates antioxidant genes and inhibits proinflammatory cytokines in rat model of overactive bladder.

PURPOSE: To study the effect of intravesical instillation of botulinum neurotoxin-A (BoNT-A) combined with low energy shock wave (LESW) for treatment of overactive bladder (OAB) in a rat model and to investigate its effect on the associated inflammatory and oxidative stress process. MATERIAL AND METHODS: Forty rats were subdivided into four equal groups: normal control group, OAB group, LESW group, and BoNT-A plus LESW group. Cystometrogram (CMG) changes and histopathological changes in the bladder mucosa were assessed in the different groups. Oxidative stress markers (malondialdehyde [MDA] and superoxide dismutase [SOD]) and proinflammatory cytokines (tumor necrotic factor-α [TNF-α] and interleukin-6 [IL-6]) were compared among groups. RESULTS: BoNT-A plus LESW group showed statistically significant lower amplitude (p = .001) and lower frequency of detrusor contractions (p = .01) compared to LESW, which showed no statistically significant difference in comparison to the OAB group. Also, the combined group significantly reduced submucosal edema and inflammatory cell infiltrate scores compared to all groups (p < .05). LESW was associated with 42% reduction of MDA expression while, LESW plus BoNT-A decreased it by 68% (p < .001). Also, LESW and LESW plus BoNT-A increased SOD expression by 43% and 75%, respectively (p < .001). LESW plus BoNT-A was associated with statistically significant lower expression of TNF-α and IL-6 expression by 37% and 66% in comparison to LESW group (p = .001). CONCLUSION: Intravesical instillation of BoNT-A plus LESW is an effective method for increasing the urothelial permeability to BoNT-A and enhancing its therapeutic effect against OAB in rat model through the expression of a substantial anti-inflammatory and antioxidative stress effect.

Can We Predict the Outcome of Oral Dissolution Therapy for Radiolucent Renal Calculi? A Prospective Study.

PURPOSE: We prospectively assessed the efficacy and the predictors of the success of oral dissolution therapy by alkalization for lucent renal calculi. MATERIALS AND METHODS: Patients with radiolucent renal stones were counseled to undergo oral dissolution therapy, which entails oral potassium citrate 20 mEq 3 times daily, 3 L daily fluid intake and a dietary regimen. The study primary end point was the achievement of a 6-month stone-free rate with oral dissolution therapy. The other end point was a change in stone surface area as measured by noncontrast computerized tomography at 3 and 6 months. RESULTS: Between February 2015 and January 2016 only 182 of the 212 eligible patients who agreed to participate were compliant with oral dissolution therapy and included in the final analysis. Mean stone surface area at enrollment was 1.3 cm (range 0.16 to 11.84). At 3 months 97 (53.2%), 65 (35.7%) and 20 (11.1%) patients were oral dissolution therapy responders (stone-free), partial responders and nonresponders, respectively. Oral dissolution therapy achieved a 6-month stone-free rate of 83%, including 97 and 54 patients after 3 and 6 months of oral dissolution therapy, respectively. On regression analysis the initial 3-month response to oral dissolution therapy (p = 0.001), lower stone density (p = 0.03) and higher urine pH 12 weeks after treatment (p = 0.01) independently predicted the oral dissolution therapy response at 6 months. CONCLUSIONS: Regardless of stone size, oral dissolution therapy was an effective treatment approach for lucent renal stones. The initial response to oral dissolution therapy after 3 months was the key factor in determining the potential oral dissolution therapy response after 6 months. In addition, treatment compliance in achieving the targeted urine pH and low stone density has an independent role in the oral dissolution therapy response.

Shock wave lithotripsy versus endoscopic cystolitholapaxy in the management of patients presenting with calcular acute urinary retention: a randomised controlled trial.

PURPOSE: Shock wave lithotripsy (SWL) in treatment of bladder and urethral stones was not precisely determined. The objective of this study is to compare the efficacy and safety of SWL versus visual cystolitholapaxy in the management of calcular acute urine retention. METHODS: From March 2015 to February 2017, a randomised controlled study was conducted on 100 patients for whom urethral catheter fixed for acute retention of urine due to urethral or vesical radio-opaque stone(s) ≤ 2 cm. Patients were randomised to either SWL group (n = 50) or visual cystolitholapaxy (endoscopy group) (n = 50). RESULTS: No statistically significant differences between the pre-operative parameters of both groups were found. The mean stone diameter was 12.2 ± 3 mm and 12.2 ± 3.2 mm in SWL and endoscopy groups, respectively (p value = 0.4). The overall success rates of SWL group were 94% (47 of 50 patients) and endoscopy group were 98% (49 of 50 patients). SWL failed in 3 patients (6%); these 3 patients underwent cystolitholapaxy and were rendered free of stones. Intra-operative and post-operative complications were comparable between both groups (p value = 0.5 and 1, respectively). One patient had bladder perforation in the endoscopy group and was managed conservatively. CONCLUSIONS: SWL mono-therapy is safe, non-invasive and as effective as visual cystolitholapaxy in management of patients presenting with acute urine retention by vesical or urethral stones 2 cm or less and could be useful for patients unwilling/unfit for general anaesthesia.

Prevalence and impact of lower urinary tract symptoms: Results of the epic survey in Egypt.

AIMS: To estimate the prevalence of lower urinary tract symptoms (LUTS), including overactive bladder (OAB), and urinary incontinence (UI), in Egypt and the impact on patients' quality of life. METHODS: A population-based, cross-sectional survey (EPIC) was conducted with a random sample of adults aged ≥18 years. Prevalence estimates were based on 2002 International Continence Society definitions. RESULTS: A total of 3600 adult men and women participated in the survey; 86% of them experienced ≥1 LUTS: storage symptoms were more frequently reported (75%) than voiding (52%) or postmicturition (42%) symptoms. The most prevalent storage symptom was nocturia (defined as ≥1 time per night) in 70% of the population. UI was reported by 21% (mixed UI [MUI]: 9%; stress UI [SUI]: 4%; urgency UI [UUI]: 5%; other UI: 3%), and 30% met criteria for OAB. Despite the high prevalence of LUTS, few individuals with UUI, MUI, SUI, or OAB took prescription medicine (12%) or consulted a healthcare professional about their symptoms (23%). CONCLUSION: High prevalence rates of LUTS and OAB were found in adult men and women in Egypt, although low healthcare utilization and low prescription medication use for symptoms were observed.

Could platelet to leucocytic count ratio (PLR) predict sepsis and clinical outcomes in patients with emphysematous pyelonephritis?

OBJECTIVES: To study risk factors for sepsis and mortality evaluating the role of platelet to leucocytic count ratio (PLR) as a marker for urosepsis and clinical outcomes in cases of emphysematous pyelonephritis (EPN). MATERIALS: Patients with EPN were retrospectively reviewed. Patients' age, sex, diabetes mellitus (DM), Body Mass Index (BMI), hydronephrosis, types of EPN, air locules volume, serum creatinine, leucocytic count, and platelet count, PLR, albumin, INR and the line of treatment were analyzed as risk factors of sepsis. Correlation between PLR and other variables was done using Pearson correlation coefficient. Univariate and multivariate analyses for sepsis and mortality were performed. RESULTS: Of fifty four patients, 38 patients had SIRS ≥2 criteria on admission. Twenty patients developed sepsis requiring ICU admission. In univariate analysis, male gender, lower BMI, higher INR, higher WBCs count and lower PLR were associated with sepsis (P = 0.0001, 0.009, 0.04, 0.003 and 0.001, respectively). In multivariate analysis, PLR ≤18.4, male sex and BMI ≤24.2 were independent risk factors. Lower PLR directly correlated with serum albumin (P = 0.01) and inversely correlated with serum creatinine and random blood glucose level and Klebsiella infection (P = 0.001, 0.007 and 0.005, respectively). Also, it was correlated with a higher total score of qSOFA and SOFA (P = 0.02 and 0.04). Lower PLR was independent risk factors for death in EPN patients with (P = 0.003). CONCLUSION: EPN is associated with sepsis development. Lower PLR is an independent simple predictor for sepsis and mortality in patients with EPN.

Pathological characteristics and prognostic indicators of different histopathological types of urinary bladder cancer following radical cystectomy in a large single-center Egyptian cohort.

OBJECTIVE: To evaluate differences in pathological features and prognostics across four bladder cancer histopathological types: urothelial carcinoma (UC), urothelial carcinoma with variant histology (UCV), squamous cell carcinoma (SCC) and adenocarcinoma (ADC), utilizing a large cohort of radical cystectomy (RC) patients. METHODS: A retrospective analysis of patients who underwent RC at a single institution in Egypt between 1997 and 2004 was performed. Kaplan-Meier and multivariable analyses were performed to evaluate the prognostic significance of pathological features including tumor stage, grade, lymphovascular invasion (LVI), and lymph node (LN) involvement in the different subtypes on disease-free survival (DFS). RESULTS: 1238 patients (975 male, 263 female) were included, of whom 577 (47%) had UC, 174 (14%) UCV, 398 (32%) SCC, and 89 (7%) ADC. Median age was 54 (20-87) years and median follow-up was 40 months (0-110). There were significant differences in stage, grade, LVI, LN involvement, and presence of schistosomiasis across the subtypes (all p < 0.05). The prognostic significance of LVI was more evident in SCC (HR 2.14, p = 0.003) and ADC (HR 2.17, p = 0.044) than in UC (HR 1.66, p = 0.008). LN involvement was the strongest prognostic factor in UCV (HR 2.14, p = 0.012). CONCLUSIONS: There are significant differences in clinicopathological features and their prognostic impact across bladder cancer subtypes. The prognostic significance of LVI is more evident in SCC and ADC, while LN involvement is more prognostic in UCV. Determining independent predictors in individual subtypes can guide multimodal treatment selection and clinical trial design.

Epidermal growth factor expression as a predictor of chemotherapeutic resistance in muscle-invasive bladder cancer.

BACKGROUND: Epidermal growth factor receptor (EGFR) overexpression is believed to be associated with bladder cancer (BC) progression and poor clinical outcomes. In vivo studies have linked EGFR subcellular trafficking and chemo-resistance to cisplatin-based chemotherapies. This has not been studied in the clinical adjuvant setting. We aimed to investigate the prognostic significance of EGFR expression in patients receiving cisplatin-based adjuvant chemotherapy following radical cystectomy for advanced BC. METHODS: The database from the Urology and Nephrology Center at Mansoura University was reviewed. BC patients who were treated with radical cystectomy and adjuvant chemotherapy for adverse pathological features or node positive disease were identified. Patients who underwent palliative cystectomy, had histological diagnoses other than pure urothelial carcinoma, or received adjuvant radiotherapy were excluded from the study. Immunohistochemical staining for EGFR expression was performed on archived bladder specimens. The following in vitro functional analyses were performed to study the relationship of EGFR expression and chemoresponse. RESULTS: The study included 58 patients, among which the mean age was 57 years old. Majority of patients had node positive disease (n = 53, 91%). Mean follow up was 26.61 months. EGFR was overexpressed in 25 cystectomy specimens (43%). Kaplan-Meier analysis revealed that EGFR over-expression significantly correlated with disease recurrence (p = 0.021). Cox proportional hazard modeling identified EGFR overexpression as an independent predictor for disease recurrence (p = 0.04). Furthermore, in vitro experiments demonstrated that inhibition of EGFR may sensitize cellular responses to cisplatin. CONCLUSIONS: Our findings suggest that EGFR overexpression is associated with disease recurrence following adjuvant chemotherapy for advanced BC. This may aid in patient prognostication and selection prior to chemotherapeutic treatment for BC.

Residual stones after percutaneous nephrolithotomy: comparison of intraoperative assessment and postoperative non-contrast computerized tomography.

OBJECTIVES: To compare the intraoperative surgeon perspective for detection of residual fragments (RFs) after percutaneous nephrolithotomy (PNL) with postoperative NCCT. METHODS: A prospective study of adult patients who underwent PNL between March and September 2014 was conducted. Stone complexity was evaluated using the Guy's stone score (GSS). All patients were evaluated by pre- and postoperative NCCT. After the procedure, the surgeon had been asked whether there were residual stones or not. The sensitivity, specificity and predictive values were tested against postoperative NCCT. Predictors of accurate intraoperative assessment were determined using univariate and multivariate statistical analyses. RESULTS: The study included 306 consecutive patients. The surgeons reported no residual stones in 236 procedures; of whom 170 (72%) were reported stone-free by NCCT. On the other hand, 65 out of 70 procedures (93%) reported with residual stones by the surgeons were true by NCCT. The sensitivity was 50% and the NPV was 72%, while the specificity was 97% and the PPV was 93%. On multivariate analysis, only lower GSS (p < 0.001) was independently associated with true negative surgeon opinion. CONCLUSIONS: Although there was a high surgeon ability to detect post-PNL residual stones, postoperative imaging is mandatory because of the high false negative rates and low NPV. The surgeon opinions can be judged only in stones with lower GSS. The NPV could be enhanced if a consistent definition of clinically significant RFs is introduced.

Intermittent Testicular Torsion in Adults: An Overlooked Clinical Condition.

OBJECTIVES: The aim of this study was to describe the management protocol for intermittent testicular torsion (ITT) in adults and report the outcome of this clinical condition, which is commonly overlooked in adults. SUBJECTS AND METHODS: Sixty-three patients were included in the study. The inclusion criterion was the presence of sudden intermittent testicular pain over a duration of 3 months. All the patients underwent clinical examination, urine analysis, culture, and scrotal ultrasound with Doppler. The testicle was in an abnormal or in transverse lie and/or could easily be twisted. Scrotal support and analgesia were given for 1 month, then patients were offered orchidopexy or conservative treatment. Nineteen patients chose orchidopexy while 44 chose conservative treatment. Follow-up ranged from 3 months to 2 years. The improvement was assessed using a visual analog pain score. The outcome of the treatment was compared between the surgical and conservative groups using a χ2 test. RESULTS: The median age of the patients was 28 years (range: 17-50). Of the 19 patients who underwent orchidopexy, the pain resolved or visual analog pain scores improved (median 1/10) in 18 (94.7%) cases. On the other hand, 21 of the 44 (47.7%) cases that chose the conservative approach claimed their pain resolved or improved (visual analog pain scores: median 3/10) with a median of 13 months of follow-up. CONCLUSION: In this study, scrotal orchidopexy proved to be superior to conservative measures in cases of ITT in adults.

Percutaneous nephrolithotomy for staghorn stones: a randomised trial comparing high-power holmium laser versus ultrasonic lithotripsy.

OBJECTIVE: To compare high-power holmium laser lithotripsy (HP-HLL) and ultrasonic lithotripsy (US-L) for disintegration of staghorn stones during percutaneous nephrolithotomy (PCNL). PATIENTS AND METHODS: A non-inferiority randomised controlled trial was conducted between August 2011 and September 2014. Inclusion criteria were patients' aged >18 years who had complete staghorn stones (branching to the three major calyces), without contraindications to PCNL. Eligible patients were randomised between two groups: HP-HLL and US- . A standard PCNL in the prone position was performed for all patients. The only difference between the treatment groups was the method of stone disintegration. In the first group (HP-HLL), a laser power of 40-60 W (2 J, 20-30 Hz) was used to pulverise the staghorn stone into very small fragments, which could pass through the Amplatz sheath with the irrigation fluid. US-L,with suction of the fragments, was used in the second group. The primary outcome (stone-free rate) was evaluated with non-contrast computed tomography after 3 months. Secondary outcomes of complications, blood transfusion, operative time, and haemoglobin deficit were compared. The outcome assessor was 'blinded' to the treatment arm. RESULTS: The study included 70 patients (35 in each group). The baseline characteristics (age, sex, body mass index, side, stone volume, and density) and operative technique (number, size of tracts, and need for second PCNL session) were comparable for both groups. Operative time was significantly shorter in US-L group, at a mean (SD) of 130 (34) vs 148.7 (35) min (P = 0.028). The haemoglobin deficit was significantly more with in the US-L group, at a mean (SD) of 1.7 (0.9) vs 1.3 (0.6) g/dL (P = 0.037). The differences in blood transfusion (17% for US-L vs 11% for HP-HLL) and the complication rates (34% for US-L vs 23% for HP-HLL) were not significant (P = 0.495 and P = 0.290, respectively). The stone-free rates at 3 months were comparable (60% for US-L and 66% for HPL-L; P = 0.621). CONCLUSIONS: Compared with US-L for intracorporeal lithotripsy of staghorn stones during PCNL, HP-HLL showed comparable safety and efficacy with a lower haemoglobin deficit but longer operative time.

Modulation of renal ischemia/reperfusion in rats by a combination of ischemic preconditioning and adipose-derived mesenchymal stem cells (ADMSCs).

The present study investigated the effects of combination of ischemic preconditioning (Ipre) and adipose-derived mesenchymal stem cells (ADMSCs) on renal ischemia-reperfusion (I-R) injury in rats. 90 male Sprague Dawley rats were divided into 5 equal groups; sham operated, control (45 min left renal ischemia), Ipre group as control group with 3 cycles of Ipre just before renal ischemia, ADMSCs-treated group (as control with ADMSCs 10(6) cells in 0.1 mL via penile vein 60 min before ischemia time), and Ipre + ADMSCs group as ADMCs group with 3 cycles of Ipre. Ipre and ADMSCs groups showed significant decrease in serum creatinine and blood urea nitrogen (BUN) and caspase-3 and CD45 expression in kidney and significant increase in HIF-1α, SDF-1α, CD31, and Ki67 expressions in kidney compared with the control group (p < 0.05). Moreover, the Ipre + ADMSCs group showed significant decrease in serum BUN and caspase-3 and CD45 expression in kidney with significant increase in HIF-1α, SDF-1α, CD31, and Ki67 expression in kidney compared with the Ipre and ADMCs groups (p < 0.05). We concluded that Ipre potentiates the renoprotective effect of ADMSCs against renal I/R injury probably by upregulation of HIF-1α, SDF-1α, CD31, and Ki67 and downregulation of caspase-3 and CD45.