Impact of Varicocele on Testicular Oxidative Stress and Sperm Parameters in Experimental Animals: A Systematic Review and Meta-Analysis.

PURPOSE: Varicocele has been associated with high seminal oxidative stress (OS), impaired semen quality, and reduced male fertility potential. However, the exact mechanism(s) underlying the development of varicocele-mediated infertility and the cause-effect relationship between varicocele and testicular dysfunction are not fully understood. The aim of this systematic review and meta-analysis (SRMA) is to investigate the impact of varicocele on testicular OS markers and sperm parameters in experimental animals with varicocele as compared to animals without varicocele. MATERIALS AND METHODS: A literature search was performed using the Scopus and PubMed databases on studies that investigated testicular OS markers and sperm parameters in animals with varicocele. The primary outcomes included malondialdehyde (MDA) (nmol/mg) levels whereas the secondary outcomes included total sperm count (×106), sperm vitality (%), total sperm motility (%), and sperm DNA fragmentation (SDF) (%). Standardized mean difference (SMD) (95% confidence interval [CI]) was chosen to express the effect size. The quality of the included studies was evaluated using the Cambridge Quality Checklist. RESULTS: Out of 76 identified articles, 6 studies on rats were included in the meta-analysis. The analysis showed a significant increase of MDA (SMD: 15.61 [1.93, 29.29]; p=0.03) in rats with varicocele vs. controls. We also observed a significant decrease in total sperm count (SMD: -17.45 [-28.97, -5.93]; p<0.01), sperm vitality (SMD: -16.41 [-26.30, -6.52]; p<0.01), total sperm motility (SMD: -17.67 [-24.90, -10.44]; p<0.01), and a significant increase of SDF (SMD: 7.41 [1.23, 13.59]; p=0.02), in rats with varicocele vs. controls. The quality of the included studies was ranked as high. CONCLUSIONS: This SRMA indicates a significant increase in levels of testicular MDA and SDF and a reduction of sperm quality in experimental animals with varicocele. These findings support the potential role of testicular OS in the development of varicocele-induced testicular damage.

Is Low-risk Prostate Cancer Really Low-risk? Consider Factors Affecting Biochemical Recurrence and Tumour Upgrade.

OBJECTIVE: To evaluate the demographics, preoperative or pathological factors, and findings of magnetic resonance imaging (MRI) to predict the factors affecting biochemical recurrence and tumour upgrade in low-risk prostate cancer. STUDY DESIGN: A descriptive study. PLACE AND DURATION OF STUDY: Department of Urology, Bolu Abant Izzet Baysal University, Bolu, Turkey, from January 2017 to December 2021. METHODOLOGY: The data of 135 patients, who underwent radical prostatectomy for low-risk prostate cancer according to prostate-specific antigen (PSA) level, biopsy result and clinical stage, were analysed. Preoperative clinicopathological factors, MRI findings, and the final pathological results were analysed. Prognostic factors affecting the biochemical recurrence in the follow-up and tumour upgrade in the final pathology according to the International Society of Urological Pathology (ISUP) were evaluated. RESULTS: Mean age and preoperative PSA level were 61.37 ± 5.53 (46-74) years and 6.74 ± 1.97 (range 1.88-9.9) ng/dL, respectively. Multivariate analysis showed that the prostate volume and diameter of lesions were statistically significant in the patients with ISUP upgrade (p=0.006, p=0.025, respectively), and surgical margin positivity in the final pathology specimen was statistically significant for biochemical recurrence (p=0.016). Logistic regression analysis revealed that prostate volume and diameter of the lesion in MRI were independent predictors of ISUP score upgrade. Receiver operating characteristic (ROC) curve analysis showed that tumour size on the MRI had 49.4% sensitivity and 77.8% specificity at 10 mm (AUC:0.634, p=0.009 for predicting). CONCLUSION: Lower prostate volume, higher diameter of lesions in multiparametric MRI and surgical margin positivity were associated factors affecting the ISUP score upgrade and biochemical recurrence. Therefore, patients should be evaluated preoperatively and patient-based factors should be considered in the choice of a treatment plan. KEY WORDS: Prostate cancer, Cancer upgrade, Tumour size.

Impact of Varicocele Repair on Semen Parameters in Infertile Men: A Systematic Review and Meta-Analysis.

PURPOSE: Despite the significant role of varicocele in the pathogenesis of male infertility, the impact of varicocele repair (VR) on conventional semen parameters remains controversial. Only a few systematic reviews and meta-analyses (SRMAs) have evaluated the impact of VR on sperm concentration, total motility, and progressive motility, mostly using a before-after analytic approach. No SRMA to date has evaluated the change in conventional semen parameters after VR compared to untreated controls. This study aimed to evaluate the effect of VR on conventional semen parameters in infertile patients with clinical varicocele compared to untreated controls. MATERIALS AND METHODS: A literature search was performed using Scopus, PubMed, Embase, and Cochrane databases following the Population Intervention Comparison Outcome (PICOS) model (Population: infertile patients with clinical varicocele; Intervention: VR [any technique]; Comparison: infertile patients with clinical varicocele that were untreated; Outcome: sperm concentration, sperm total count, progressive sperm motility, total sperm motility, sperm morphology, and semen volume; Study type: randomized controlled trials and observational studies). RESULTS: A total of 1,632 abstracts were initially assessed for eligibility. Sixteen studies were finally included with a total of 2,420 infertile men with clinical varicocele (1,424 patients treated with VR vs. 996 untreated controls). The analysis showed significantly improved post-operative semen parameters in patients compared to controls with regards to sperm concentration (standardized mean difference [SMD] 1.739; 95% CI 1.129 to 2.349; p<0.001; I²=97.6%), total sperm count (SMD 1.894; 95% CI 0.566 to 3.222; p<0.05; I²=97.8%), progressive sperm motility (SMD 3.301; 95% CI 2.164 to 4.437; p<0.01; I²=98.5%), total sperm motility (SMD 0.887; 95% CI 0.036 to 1.738; p=0.04; I²=97.3%) and normal sperm morphology (SMD 1.673; 95% CI 0.876 to 2.470; p<0.05; I²=98.5%). All the outcomes showed a high inter-study heterogeneity, but the sensitivity analysis showed that no study was sensitive enough to change these results. Publication bias was present only in the analysis of the sperm concentration and progressive motility. No significant difference was found for the semen volume (SMD 0.313; 95% CI -0.242 to 0.868; I²=89.7%). CONCLUSIONS: This study provides a high level of evidence in favor of a positive effect of VR to improve conventional semen parameters in infertile men with clinical varicocele. To the best of our knowledge, this is the first SRMA to compare changes in conventional semen parameters after VR with changes in parameters of a control group over the same period. This is in contrast to other SRMAs which have compared semen parameters before and after VR, without reference to a control group. Our findings strengthen the available evidence and have a potential to upgrade professional societies' practice recommendations favoring VR to improve conventional semen parameters in infertile men.

Consensus and Diversity in the Management of Varicocele for Male Infertility: Results of a Global Practice Survey and Comparison with Guidelines and Recommendations.

PURPOSE: Varicocele is a common problem among infertile men. Varicocele repair (VR) is frequently performed to improve semen parameters and the chances of pregnancy. However, there is a lack of consensus about the diagnosis, indications for VR and its outcomes. The aim of this study was to explore global practice patterns on the management of varicocele in the context of male infertility. MATERIALS AND METHODS: Sixty practicing urologists/andrologists from 23 countries contributed 382 multiple-choice-questions pertaining to varicocele management. These were condensed into an online questionnaire that was forwarded to clinicians involved in male infertility management through direct invitation. The results were analyzed for disagreement and agreement in practice patterns and, compared with the latest guidelines of international professional societies (American Urological Association [AUA], American Society for Reproductive Medicine [ASRM], and European Association of Urology [EAU]), and with evidence emerging from recent systematic reviews and meta-analyses. Additionally, an expert opinion on each topic was provided based on the consensus of 16 experts in the field. RESULTS: The questionnaire was answered by 574 clinicians from 59 countries. The majority of respondents were urologists/uro-andrologists. A wide diversity of opinion was seen in every aspect of varicocele diagnosis, indications for repair, choice of technique, management of sub-clinical varicocele and the role of VR in azoospermia. A significant proportion of the responses were at odds with the recommendations of AUA, ASRM, and EAU. A large number of clinical situations were identified where no guidelines are available. CONCLUSIONS: This study is the largest global survey performed to date on the clinical management of varicocele for male infertility. It demonstrates: 1) a wide disagreement in the approach to varicocele management, 2) large gaps in the clinical practice guidelines from professional societies, and 3) the need for further studies on several aspects of varicocele management in infertile men.

Efficacy of intravesical cocktail therapy with or without dimethyl sulphoxide in interstitial cystitis.

Introduction: Interstitial cystitis (IC) is a chronic bladder inflammation with unknown etiologies that impairs the quality of life of patients. We aimed to investigate the efficacy of dimethyl sulphoxide (DMSO) use in the cocktail therapy in IC patients. Material and methods: Patients treated with intravesical cocktail therapy which contained a mixture of 10 mL of bupivacaine, 1 mL of heparin, and 9 mL of sodium bicarbonate, was introduced to Group 1, and, 25 mL of DMSO was added to this cocktail and introduced to Group 2. Statistical analyses between groups were assessed by Turkish validated O'Leary Sant score composed of IC Symptom Index (ICSI) and IC Problem Index (ICPI), visual analog scale (VAS) score, and short form-36 (SF-36) questionnaire in the baseline versus post-instillation week 6, month 6, and month 12, comparatively. Results: A total of 62 patients (58 women and 4 men) with a median age of 52 (28-76) years were included. Baseline versus post-instillation 6th week of ICSI and ICPI scores were 15 ±3.4 vs 7.4 ±2.9 and 12.6 ±2.8 vs 6.1 ±2.7, respectively (p <0.001 and <0.001, respectively). VAS scores of Group 2 were statistically significantly lower than that of Group 1 in the post-instillation month 6 (p = 0.03) whereas, the baseline of VAS scores were similar. Conclusions: Intravesical cocktail therapy is an effective and reliable treatment method and can be safely applied with or without DMSO. Adding DMSO to cocktail therapy provides a further decrease in VAS score in the post-instillation month 6.

Analyzing the quality and validity of holmium laser enucleation of prostate (HoLEP) videos on social media.

INTRODUCTION: The number of social media users is gradually increasing, and they are spending their time gathering a lot of useful information for themselves. Here, we analysed the quality of Holmium Laser Enucleation of Prostate (HoLEP) surgery videos on YouTube. AIM: To assess the quality of the most viewed HoLEP videos on YouTube using validated questionnaires and scoring systems developed to evaluate the significant features. MATERIAL AND METHODS: The most viewed 98 videos were included in this study by the search for 'Holep' keyword on YouTube. The Journal of American Medical Association Benchmark Score (JAMAS) and Global Quality Score (GQS) were used to analyse the videos after the validated HoLEP Scoring System Score (HSSS) was performed by 3 HoLEP trained surgeons to evaluate the technical quality of videos. RESULTS: The videos including surgical technique (76.5%) and uploaded by urologists (63.3%) constituted the majority of videos. The median of JAMAS, GQS, and HSSS were 1 (0-3), 2 (0-4), and 1.5 (0-11), respectively. The mean GQS and JAMAS of videos uploaded by academic centres was higher than those uploaded by commercial centres and urologists (p = 0.01; p = 0.01, respectively). The mean HSSS was lower in the videos uploaded in the last 5 years, while JAMAS was higher (p = 0.03, p = 0.005, respectively). The mean GQS and HSSS of videos with higher likes were found statistically significantly higher (p = 0.01; p = 0.02, respectively). CONCLUSIONS: HoLEP videos on YouTube are not adequate to obtain proper information about the surgery. Videos uploaded by academic centres and in recent years provide more valid information for patients and urologists. To increase the value of information, online materials need to be checked, for patients to access accurate, reliable, and appropriate healthcare information.

Evaluating the Effects of Subnormothermic Perfusion with AP39 in a Novel Blood-Free Model of Ex Vivo Kidney Preservation and Reperfusion.

The use of blood for normothermic and subnormothermic kidney preservation hinders the translation of these approaches and promising therapeutics. This study evaluates whether adding hydrogen sulfide donor AP39 to Hemopure, a blood substitute, during subnormothermic perfusion improves kidney outcomes. After 30 min of renal pedicle clamping, porcine kidneys were treated to 4 h of static cold storage (SCS-4 °C) or subnormothermic perfusion at 21 °C with Hemopure (H-21 °C), Hemopure + 200 nM AP39 (H200nM-21 °C) or Hemopure + 1 µM AP39 (H1µM-21 °C). Then, kidneys were reperfused with Hemopure at 37 °C for 4 h with metabolic support. Perfusate composition, tissue oxygenation, urinalysis and histopathology were analyzed. During preservation, the H200nM-21 °C group exhibited significantly higher urine output than the other groups and significantly higher tissue oxygenation than the H1µM-21 °C group at 1 h and 2h. During reperfusion, the H200nM-21 °C group exhibited significantly higher urine output and lower urine protein than the other groups. Additionally, the H200nM-21 °C group exhibited higher perfusate pO2 levels than the other groups and significantly lower apoptotic injury than the H-21 °C and the H1µM-21 °C groups. Thus, subnormothermic perfusion at 21 °C with Hemopure + 200 nM AP39 improves renal outcomes. Additionally, our novel blood-free model of ex vivo kidney preservation and reperfusion could be useful for studying other therapeutics.

Outcomes of ureterolysis for primary retroperitoneal fibrosis: A single-center experience.

OBJECTIVE: To report our experience with ureterolysis for the management of retroperitoneal fibrosis. METHODS: The data of 25 patients who underwent ureterolysis due to primary retroperitoneal fibrosis between 2002 and 2017 were reviewed retrospectively. Initial symptoms, laterality, renal function status (initial/final), operation complications and serum creatinine levels (diagnosis/preoperative/6 months, 12 months postoperatively) were recorded. After surgery, patients were followed up by ultrasonography and serum creatinine levels. Patients with impaired results underwent furosemide renogram and/or late phase of computed tomography. Factors affecting final serum creatinine levels were evaluated. The χ2 -test was used for nominal data among groups. The level of statistical significance was set as P < 0.05. RESULTS: A total of 19 patients (76%) were operated bilaterally. The mean follow-up period was 46.2 ± 9.2 months. Among 44 operated renal units, non-functioning kidney developed in seven (15.9%). A total of 34 renal units (77.3%) did not require any additional surgical intervention, and two underwent balloon dilatation (4.5%), one (2.25%) followed with double J stent changes. Two patients developed end-stage renal disease secondary to bilateral unresolved obstruction. High final serum creatinine levels developed in eight (32%) patients without dialysis. Eight patients (32%) were treated with immunosuppressive therapy for systemic recurrence. There was a significant relationship between preoperative serum creatinine levels with final serum creatinine levels (P = 0.005). There was no statistically significant relationship between diagnosis serum creatinine levels with final serum creatinine levels and postoperative dialysis requirement (P = 0.79 and P = 0.817, respectively). CONCLUSIONS: Ureterolysis provides acceptable success with low complication rates in patients with retroperitoneal fibrosis. Preoperative high-serum creatinine levels can be considered as a risk factor for long-term renal impairment and these patients should be followed closely.

Donor Nephrectomy May Compromise the Cardiovascular System: A Retrospective, Single-Center Study.

OBJECTIVES: Our goal was to determine the short-term effects of donor nephrectomy on the cardiovascular system and to gain a better understanding of the recently recognized long-term increased risk of end-stage renal disease and cardiovascular mortality. MATERIALS AND METHODS: Living kidney donors who underwent donor nephrectomy between January 2010 and January 2015 at the Hacettepe University Transplantation Unit were retrospectively screened. Echocardiographic parameters, kidney volumes, and renal functions before nephrectomy were compared with measurements after nephrectomy. Flow-mediated dilatation values of living kidney donors were compared with healthy individuals. RESULTS: The study included 73 female and 31 male living kidney donors with a mean age of 46.1 ± 10.8 years. In the comparative analysis of donors versus 35 healthy individuals, the changes in flow-mediated dilatation were 12.3 ± 5.7% and 15.4 ± 6.3%, respectively (P = .016). In the comparative analysis of preoperative versus the last visit transthoracic echocardiographic results, left ventricular end-systolic and end-diastolic diameters decreased and left ventricular posterior wall thickness and septum thickness increased (P = .025, P = .002, P = .026, and P = .019, respectively). CONCLUSIONS: Nephrectomy may cause several hemodynamic changes in living kidney donors, which may exacerbate cardiovascular risks in this population.

Patterns of Expression of H2S-Producing Enzyme in Human Renal Cell Carcinoma Specimens: Potential Avenue for Future Therapeutics.

BACKGROUND: Renal cell carcinoma (RCC) is the most common cancer of the kidney. The most common histotype is clear-cell (cc) RCC. Hydrogen sulfide (H2S) is an angiogenic and anti-apoptotic gasotransmitter that is elevated under pseudohypoxic conditions. H2S is endogenously produced by three enzymes: Cystathionine γ-lyase (CSE), cystathionine ß-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (MPST). Seeing as increased expression of these enzymes has been observed in other human cancer types, this study aimed to quantify H2S-producing enzyme expression in human RCC samples and evaluate whether it correlated with clinical outcomes. PATIENTS AND METHODS: Eighty-eight human kidney tissue specimens, with healthy and cancerous tissue components, were immunohistochemically stained for CSE, CBS, and MPST. The mean pixel intensity of positively stained areas was quantified. A retrospective analysis was conducted to obtain patient demographics, rates of metastasis/recurrence, and prognostic characteristics. Statistical correlations between enzyme expressions and subsequent patient outcomes were evaluated. RESULTS: There was significantly greater expression of CSE, CBS, and MPST in cc-RCC compared to paired healthy tissue (p<0.0001). The difference in expression of CSE in cancerous versus normal tissue was significantly greater than that for CBS and MPST (p<0.0001 and p<0.01, respectively). Enzyme expression patterns in cancerous versus normal tissue did not correlate with nuclear grade, stage, histological type or cancer recurrence/metastasis. CONCLUSION: To our knowledge, this is the first report of the differential increase in expression of CSE, CBS, and MPST in human RCC. Although these patterns do not appear to correlate with cancer recurrence, metastasis, size or nuclear grade, their differential increase suggests a potential therapeutic target.

Hydrogen Sulfide: Emerging Role in Bladder, Kidney, and Prostate Malignancies.

Hydrogen sulfide (H2S) is the latest member of the gasotransmitter family and known to play essential roles in cancer pathophysiology. H2S is produced endogenously and can be administered exogenously. Recent studies showed that H2S in cancers has both pro- and antitumor roles. Understanding the difference in the expression and localization of tissue-specific H2S-producing enzymes in healthy and cancer tissues allows us to develop tools for cancer diagnosis and treatment. Urological malignancies are some of the most common cancers in both men and women, and their early detection is vital since advanced cancers are recurrent, metastatic, and often resistant to treatment. This review summarizes the roles of H2S in cancer and looks at current studies investigating H2S activity and expression of H2S-producing enzymes in urinary cancers. We specifically focused on urothelial carcinoma, renal cell carcinoma, and prostate cancer, as they form the majority of newly diagnosed urinary cancers. Recent studies show that besides the physiological activity of H2S in cancer cells, there are patterns between the development and prognosis of urinary cancers and the expression of H2S-producing enzymes and indirectly the H2S levels. Though controversial and not completely understood, studying the expression of H2S-producing enzymes in cancer tissue may represent an avenue for novel diagnostic and therapeutic strategies for addressing urological malignancies.

Toxicity, Adverse Events, and Quality of Life Associated with the Treatment of Metastatic Castration-Resistant Prostate Cancer.

OBJECTIVES: Among males, prostate cancer (PCa) is the most common cancer in Europe and the second most common cancer worldwide, especially in those aged > 70 years. With the advent of novel alternative treatments, survival in patients with advanced PCa has increased. PCa is now considered a chronic disease. Survival is an important endpoint in advanced PCa, as is quality of life (QoL). The effects of the disease and its treatment on patient health-related QoL must be taken into account when selecting the most appropriate treatment options. The present literature review aimed to provide an overview of metastatic castration-resistant prostate cancer treatment modalities, with an emphasis on side effect profiles and general health-related QoL. METHODS: PubMed was searched using the keywords metastatic castration-resistant prostate cancer, docetaxel, cabazitaxel, enzalutamide, abiraterone acetate, and QoL. CONCLUSION: Based on the studies reviewed herein, abiraterone acetate and enzalutamide provide favorable outcomes, in terms of hematological adverse events. As enzalutamide and abiraterone acetate can be taken orally, they might have a positive effect on patient QoL.

Do the expressions of epithelial-mesenchymal transition proteins, periostin, integrin-α4 and fibronectin correlate with clinico-pathological features and prognosis of metastatic castration-resistant prostate cancer?

Development of metastatic castration-resistant prostate cancer is a result of the lack of an apoptotic response by the tumor cells and loss of the ability to stick to adjacent cells through epithelial-mesenchymal transition. Although there are several strongly recommended biomarkers for determining prognosis of metastatic castration-resistant prostate cancer, only few of them may help decide the selection of the optimal treatment option. The mode of treatment sequencing in metastatic castration-resistant prostate cancer will be based on the individual characteristics of the patient. In this study, we aimed to explain the correlation between the expression characteristics of periostin, integrin-α4, and fibronectin in metastatic castration-resistant prostate cancer patients and their clinico-pathological data comprising Gleason score, PSA levels, and metastatic sites in the process of epithelial-mesenchymal transition. We evaluated by using Western blotting, periostin, integrin-α4, and fibronectin expressions in peripheral blood samples of metastatic castration-resistant prostate cancer patients ( n = 40), benign prostatic hyperplasia patients ( n = 20), and the healthy control group ( n = 20). Associations between changes in the protein expressions and clinico-pathological parameters were also analyzed in the metastatic castration-resistant prostate cancer group. When comparing BPH and healthy groups with the metastatic castration-resistant prostate cancer group, a reduced expression of integrin-α4 was found in metastatic patients, albeit being statistically insignificant ( P > 0.05). Protein expressions of periostin and fibronectin in the metastatic castration-resistant prostate cancer group were higher than those in the BPH and heathy groups ( P < 0.001). Increased periostin expression in metastatic patients was significantly associated with bone metastasis ( P < 0.05). Elevated periostin and fibronectin levels in metastatic castration-resistant prostate cancer patients may be appropriate targets of therapeutic intervention in the future. Impact statement Prostate cancer is the third most common cancer in the world and the most common cancer among men. Development of metastatic castration-resistant prostate cancer (mCRPC) is a result of the lack of an apoptotic response by the tumor cells and loss of the ability to stick to adjacent cells through epithelial-mesenchymal transition (EMT). The present study analyzes for the first time the expressions of EMT marker proteins - periostin, integrin α4, fibronectin - in mCRPC and in benign prostatic hyperplasia (BPH) with the aim to determine the clinical relevance of changes in these three proteins vis-a-vis the PCa aggressive phenotype. In doing so, it sheds light on the molecular mechanism underlying the disease. We concluded that elevated periostin and fibronectin levels in mCRPC patients may be appropriate targets of therapeutic intervention in the future; hence, adopting methods that target these proteins may help treat prostate cancer effectively.

Invasive Squamous Carcinoma and Adenocarcinoma of an Unreconstructed Exstrophic Bladder with HPV Infection.

Bladder exstrophy is a complex abnormality and is traditionally treated within the early years of life. It is associated with an increased risk of bladder cancer, with 95% of the arising tumors being adenocarcinomas and 3 to 5% being squamous cell carcinomas. HPV infections are also associated with an increased risk of bladder cancer. This case represents a patient with bladder exstrophy that gave rise to coinciding squamous cell carcinoma and adenocarcinoma. Final pathology results showed an infection with HPV. We presented the management of the case and discussed the diagnosis and treatment methods for this patient.