Photobiomodulation as a Potential Therapy for Erectile Function: A Preclinical Study in a Cavernous Nerve Injury Model.

PURPOSE: To identify the optimal photobiomodulation (PBM) parameters using molecular, histological, and erectile function analysis in cavernous nerve injury. MATERIALS AND METHODS: A cavernous nerve injury was induced in 8-week-old C57BL/6J male mice that were subsequently divided randomly into age-matched control groups. Erectile function tests, penile histology, and Western blotting were performed 2 weeks after surgery and PBM treatment. RESULTS: The PBM treatment was administered for five consecutive days with a light-emitted diode (LED) device that delivers 660 nm±3% RED light, and near infra-red 830 nm±2% promptly administered following nerve-crushing surgery and achieved a notable restoration of erectile function approximately 90% of the control values. Subsequent in-vitro and ex-vivo analyses revealed the regeneration of neurovascular connections in both the dorsal root ganglion and major pelvic ganglion, characterized by the sprouting of neurites. Furthermore, the expression levels of neurotrophic, survival, and angiogenic factors exhibited a substantial increase across all groups subjected to PBM treatment. CONCLUSIONS: The utilization of PBM employing LED with 660 nm, 830 nm, and combination of both these wavelengths, exhibited significant efficacy to restore erectile function in a murine model of cavernous nerve injury. Thus, the PBM emerges as a potent therapeutic modality with notable advantages such as efficacy, noninvasiveness, and non-pharmacological interventions for erectile dysfunction caused by nerve injury.

Urolithiasis in Kidney Transplant Patients: A Multicenter KSER Research Series.

Background and Objectives: Urolithiasis occurrence is uncommon in kidney transplantation patients, though it has serious implications, including acute kidney injury in the transplanted kidney. This study investigates the leading causes of urolithiasis in kidney transplantation patients, the diagnostic process, and the outcomes of multimodal management. Materials and Methods: Data collection spanned from January 1997 to December 2021, involving kidney transplantation patients with urolithiasis from the database of the Korean Society of Endourology and Robotics (KSER) research committee. Analysis encompassed factors triggering urolithiasis, the diagnostic process, stone attributes, treatment methods, and outcomes. Results: Our analysis included 58 kidney transplantation patients with urolithiasis from eight medical centers. Of these patients, 37 were male and 4 had previous urolithiasis diagnoses. The mean age was 59.09 ± 10.70 years, with a mean duration from kidney transplantation to diagnosis of 76.26 ± 183.14 months. The most frequent method of stone detection was through asymptomatic routine check-ups (54.7%). Among the 58 patients, 51 underwent stone treatment. Notably, 95.3% of patients with ureter stones received treatment, a significantly higher rate than the 66.7% of patients with renal stones (p = 0.010). Success rates showed no significant differences between renal (70%) and ureter stone (78.0%) groups (p = 0.881). Conclusions: Urolithiasis in transplanted kidneys constitutes an acute condition requiring emergency intervention. Endo-urological interventions are effective for kidney transplantation patients with urolithiasis. To ensure prevention and early detection, diligent follow-up and routine imaging tests are necessary.

BMP2 restores erectile dysfunction through neurovascular regeneration and fibrosis reduction in diabetic mice.

BACKGROUND: The odds of erectile dysfunction are three times more prevalent in diabetes. Severe peripheral vascular and neural damage in diabetic patients responds poorly to phosphodiesterase-5 (PDE5) inhibitors. However, bone morphogenetic protein 2 is known to be involved in angiogenesis. OBJECTIVES: To assess the efficacy of bone morphogenetic protein 2 in stimulating angiogenesis and augmenting nerve regeneration in a mouse model of diabetic-induced erectile dysfunction. MATERIALS AND METHODS: The induction of diabetes mellitus was performed by streptozotocin (50 mg/kg daily) administered intraperitoneally for 5 successive days to male C57BL/6 mice that were 8 weeks old. Eight weeks post-inductions, animals were allocated to one of five groups: a control group, a streptozotocin-induced diabetic mouse group receiving two intracavernous 20 µL phosphate-buffered saline injections, or one of three bone morphogenetic protein 2 groups administered two injections of bone morphogenetic protein 2 protein (1, 5, or 10 µg) diluted in 20 µL of phosphate-buffered saline within a 3-day interval between the first and second injections. The erectile functions were assessed 2 weeks after phosphate-buffered saline or bone morphogenetic protein 2 protein injections by recording the intracavernous pressure through cavernous nerve electrical stimulation. Angiogenic activities and nerve regenerating effects of bone morphogenetic protein 2 were determined in penile tissues, aorta, vena cava, the main pelvic ganglions, the dorsal roots, and from the primary cultured mouse cavernous endothelial cells. Moreover, fibrosis-related factor protein expressions were evaluated by western blotting. RESULTS: Erectile function recovery to 81% of the control value in diabetic mice was found with intracavernous bone morphogenetic protein 2 injection (5 µg/20 µL). Pericytes and endothelial cells were extensively restored. It was confirmed that angiogenesis was promoted in the corpus cavernosum of diabetic mice treated with bone morphogenetic protein 2 through increased ex vivo sprouting of aortic rings, vena cava and penile tissues, and migration and tube formation of mouse cavernous endothelial cells. Bone morphogenetic protein 2 protein enhanced cell proliferation and reduced apoptosis in mouse cavernous endothelial cells and penile tissues, and promoted neurite outgrowth in major pelvic ganglia and dorsal root ganglia under high-glucose conditions. Furthermore, bone morphogenetic protein 2 suppressed fibrosis by reducing mouse cavernous endothelial cell fibronectin, collagen 1, and collagen 4 levels under high-glucose conditions. CONCLUSION: Bone morphogenetic protein 2 modulates neurovascular regeneration and inhibits fibrosis to revive the mouse erection function in diabetic conditions. Our findings propose that the bone morphogenetic protein 2 protein represents a novel and promising approach to treating diabetes-related erectile dysfunction.

The Consecutive 200 Cases of Endoscopic-Combined Intrarenal Surgery: Comparison between Standard and Miniature Surgeries.

Background and Objectives: Percutaneous nephrolithotomy (PCNL) is still the gold-standard treatment for large and/or complex renal stones. Endoscopic combined intrarenal surgery (ECIRS) was developed with the goal of minimizing the number of access tracts of PCNL while simultaneously improving the one-step stone-free rate (SFR). The aim of this study was to share the experience of the consecutive 200 cases of ECIRS in one institute and analyze surgical outcomes of mini-ECIRS and standard ECIRS. Materials and Methods: We performed ECIRS for 200 adult patients between July 2017 and January 2020. An ECIRS was performed with the patient under general anesthesia in the intermediate-supine position. Surgeries were finished using a tubeless technique with a simple ureteral stent insertion. Results: There were significant differences in the mean maximal stone length (MSL), the variation coefficient of stone density (VCSD), the linear calculus density (LCD), the Seoul National University Renal Stone Complexity (S-ReSC), and the modified S-ReSC scores in stone characteristics, and estimated blood loss (EBL) and operation time in peri-operative outcomes between conventional and mini-ECIRS. After propensity-score matching, there was only a difference in EBL between the two groups. In logistic regression models, MSL [odds ratio (OR) 0.953; 95% confidence interval (CI) 0.926-0.979; p < 0.001], LCD (OR 4.702; 95% CI 1.613-18.655; p = 0.013) were significant factors for the success rate after ECIRS. Conclusions: In patients who underwent a mini-ECIRS, the stones were relatively smaller and less complex, and the operation time was shorter. However, if the size of stones was similar, there was no difference in the success rate, but EBL was lower in mini-ECIRS than in standard surgery.

Regenerative therapies as a potential treatment of erectile dysfunction.

Erectile dysfunction (ED) is the most common sexual dysfunction disease in adult males. ED can be caused by many factors, such as vascular disease, neuropathy, metabolic disturbances, psychosocial causes, and side effects of medications. Although current oral phosphodiesterase type 5 inhibitors can achieve a certain effect, they cause temporary dilatation of blood vessels with no curative treatment effects. Emerging targeted technologies, such as stem cell therapy, protein therapy, and low-intensity extracorporeal shock wave therapy (Li-ESWT), are being used to achieve more natural and long-lasting effects in treating ED. However, the development and application of these therapeutic methods are still in their infancy, and their pharmacological pathways and specific mechanisms have not been fully discovered. This article reviews the preclinical basic research progress of stem cells, proteins, and Li-ESWT therapy, as well as the current status of clinical application of Li-ESWT therapy.

Cytoreductive prostatectomy may improve oncological outcomes in patients with oligometastatic prostate cancer: An updated systematic review and meta-analysis.

The oncologic outcomes of cytoreductive prostatectomy (CRP) in oligometastatic prostate cancer (OmPCa) are still controversial. Therefore, we conducted a systematic review and meta-analysis on the oncologic outcome of CRP in OmPCa. OVID-Medline, OVID-Embase, and Cochrane Library databases were searched to identify eligible studies published before January 2023. A total of 11 studies (929 patients), 1 randomized controlled trial (RCT) and 10 non-RCT studies, were included in the final analysis. RCT and non-RCT were further analyzed separately. End points were progression-free-survival (PFS), time to castration-resistant prostate cancer (CRPCa), cancer-specific-survival (CSS) and overall-survival (OS). It was analyzed using hazard ratio (HR) and 95% confidence intervals (CIs). In PFS, in RCT, HR=0.43 (CIs=0.27-0.69) was shown statistically significant, but in non-RCTs, HR=0.50 (CIs=0.20-1.25), there was no statistical difference. And, in time to CRPCa was statistically significant in the CRP group in all analyses (RCT; HR=0.44; CIs=0.29-0.67) (non-RCTs; HR=0.64; CIs=0.47-0.88). Next, CSS was not statistically different between the two groups (HR=0.63; CIs=0.37-1.05). Finally, OS showed better results in the CRP group in all analyses (RCT; HR=0.44; CIs=0.26-0.76) (non-RCTs; HR=0.59; CIs=0.37-0.93). Patients who received CRP in OmPCa showed better oncologic outcomes compared to controls. Notably, time to CRPC and OS showed significantly improved compared with control. We recommend that experienced urologists who are capable of managing complications consider CRP as a strategy to achieve good oncological outcomes in OmPCa. However, since most of the included studies are non-RCT studies, caution should be exercised in interpreting the results.

Silodosin versus Tamsulosin for Medical Expulsive Therapy of Ureteral Stones: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background and Objectives: This systematic review and meta-analysis of randomized controlled trials was performed to compare the therapeutic effects and safety profiles of silodosin and tamsulosin for medical expulsive therapy (MET) of ureteral stones. Materials and Methods: We searched PubMed, EMBASE, the Cochrane Library, and Web of Science to identify articles published before July 2022 that described randomized controlled trials comparing silodosin and tamsulosin for MET of ureteral stones. Endpoints were stone expulsion rate, stone expulsion time, and total complication rate. Results: In total, 14 studies were included in our analysis. The size of ureteral stones was <1 cm. Compared with tamsulosin, silodosin resulted in a significantly higher stone expulsion rate (p < 0.01, odds ratio (OR) = 2.42, 95% confidence interval (CI) = 1.91 to 3.06, I2 = 0%) and significantly shorter stone expulsion time (p < 0.01, mean difference = −3.04, 95% CI = −4.46 to −1.63, I2 = 89%). The total complication rate did not significantly differ between silodosin and tamsulosin (p = 0.33, OR = 1.15, 95% CI = 0.87 to 1.52, I2 = 7%). Conclusions: Compared with tamsulosin, silodosin resulted in significantly better expulsion of ureteral stones <1 cm. The total complication rate did not significantly differ between silodosin and tamsulosin. Thus, silodosin may be superior to tamsulosin for MET of ureter stones <1 cm.

Surveillance versus Adjuvant Treatment with Chemotherapy or Radiotherapy for Stage I Seminoma: A Systematic Review and Meta-Analysis According to EAU COVID-19 Recommendations.

Background and Objectives: During the coronavirus disease 2019 (COVID-19) outbreak, the European Association of Urology (EAU) Guidelines Office Rapid Reaction Group (GORRG) recommended that patients with clinical stage I (CSI) seminoma be offered active surveillance (AS). This meta-analysis aimed to evaluate the efficacy of AS versus adjuvant treatment with chemotherapy or radiotherapy for improving the overall survival (OS) of CSI seminoma patients. Materials and Methods: A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The PubMed/Medline, EMBASE, and Cochrane Library databases were searched. The primary outcome was 5-year OS, and the secondary outcome was the 5-year relapse-free survival (RFS). The outcomes were analyzed as odds ratios (ORs) and 95% confidence intervals (CIs). Results: A total of 14 studies were included. Overall, the quality scores were relatively high, and little publication bias was noted. In terms of the 5-year OS, 7 studies were analyzed; there was no significant difference between AS and adjuvant treatment (OR, 0.99; 95% CI, 0.41−2.39; p = 0.97). In terms of 5-year RFS, 12 studies were analyzed. Adjuvant treatment reduced the risk of 5-year recurrence by 85% compared with AS (OR, 0.15; 95% CI, 0.08−0.26; p < 0.001). Conclusions: In terms of the OS in CSI seminoma patients, no intergroup difference was noted, so it is reasonable to offer AS, as recommended by the EAU GORRG until the end of the COVID-19 pandemic. However, since there is a large intergroup difference in the recurrence rate, further research on the long-term (>5 years) outcomes is warranted.

Effects of intravesical BCG maintenance therapy duration on recurrence rate in high-risk non-muscle invasive bladder cancer (NMIBC): Systematic review and network meta-analysis according to EAU COVID-19 recommendations.

PURPOSE: During the coronavirus disease 2019 (COVID-19) pandemic, the European Association of Urology (EAU) recommended that courses of intravesical bacillus Calmette-Guérin (BCG) therapy lasting more than 1 year could be safely terminated for patients with high-risk non-muscle-invasive bladder cancer (NMIBC). Thus, we conducted a systematic review and network meta-analysis according to EAU's COVID-19 recommendations. MATERIALS AND METHODS: A systematic review was performed following the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. We conducted a network meta-analysis of recurrence rate in patients with NMIBC receiving induction therapy (M0) and those receiving maintenance therapy lasting 1 year (M1) and more than 1 year (M2). RESULTS: Nineteen studies of 3,957 patients were included for the network meta-analysis. In a node-split forest plot using Bayesian Markov Chain Monte Carlo (MCMC) modeling, there were no differences between the M1 and M2 groups in recurrence rate [odds ratio (OR) 0.95 (0.73-1.2)]. However, recurrence rate in the M0 group was higher than that in the M1 [OR 1.9 (1.5-2.5)] and M2 [OR 2.0 (1.7-2.4)] groups. P-score tests using frequentist inference to rank the treatments in the network demonstrated that the therapy used in the M2 group (P-score 0.8701) was superior to that used in the M1 (P-score 0.6299) and M0 groups (P-score 0). In rank-probability tests using MCMC modeling, the M2 group showed the highest rank, followed by the M1 and M0 groups. CONCLUSION: In the network meta-analysis, there were no differences between those receiving BCG maintenance therapies in terms of recurrence rate. In the rank tests, therapy lasting more than 1-year appears to be most effective. During the COVID-19 pandemic, 1-year maintenance therapy can be used, but after the COVID-19 pandemic, therapy lasting more than 1-year could be beneficial.

Efficacy of Low-Intensity Extracorporeal Shock Wave Treatment in Erectile Dysfunction Following Radical Prostatectomy: A Systematic Review and Meta-Analysis.

Erectile dysfunction (ED) is a well-known complication of radical prostatectomy (RP). Oral 5-phosphodiesterase inhibitors are currently the most widely used penile rehabilitation treatment for ED following RP, but they are less effective than for those with general ED. Low-intensity extracorporeal shock wave treatment (LI-ESWT), causing a biological change that induces neovascularization, has recently been used as a treatment for ED. Therefore, we conducted a systematic review and meta-analysis to investigate the efficiency of LI-ESWT in ED following RP. PubMed, Embase, and the Cochrane Library were searched up until December 2021. The endpoint was the change in IIEF scores after LI-ESWT. Five papers (460 patients) were included in the final analysis. In IIEF scores performed 3-4 months after LI-ESWT, the group receiving LI-ESWT showed statistically significantly better results than the control (WMD = -2.04; 95% CI, -3.72 to -0.35; p = 0.02). However, there were a total of two studies that measured the results after 9-12 months. There was no statistical difference between the two groups (WMD = -5.37; 95% CI, -12.42 to 1.69; p = 0.14). The results of this analysis indicate that LI-ESWT showed a statistically significant effect on early recovery in penile rehabilitation of ED following RP. However, the level of evidence was low. Therefore, careful interpretation of the results is required.

Outcomes of Retzius-sparing versus conventional robot-assisted radical prostatectomy: A KSER update series systematic review and meta-analysis.

BACKGROUND: Robotic-assisted radical prostatectomy(RARP) is widely used to surgically treat of localized prostate cancer. Among RARP, retzius-sparing techniques(RS-RARP) are implemented through douglas pouch, not the existing conventional approach(C-RARP). We conducted an updated systematic review and meta-analysis including recent published papers. MATERIALS & METHODS: Systematic review was performed following the PRISMA guideline. PubMed, EMBASE, and Cochrane Library were searched up to August 2021. We conducted meta-analysis as follows; Participants, patients with biopsy-proven PCa; Interventions, Patients underwent C-RARP or RS-RALP; Outcomes, comparison of continence recovery rate, positive surgical margins(PSM), complication, operation time and estimated blood loss(EBL) included for analysis. RESULTS: Thirteen studies with a total of 2917 patients were included for meta-analysis. Among them, three were randomized controlled trials (RCT) studies and the rest were non-RCT studies. Incontinence was analyzed with zero pad and safety pad, respectively. There showed a statistically significant advantage for RS-RARP in terms of continence recovery at 1 month(0 pad; OR 0.28, (0.16-0.47), safety-pad; OR 0.12 (0.07-0.22), p<0.001), as well as at 3 months(0 pad; OR 0.31 (0.18-0.53), safety-pad; OR 0.23 (0.14-0.40) p<0.001), 6 months(0 pad; OR 0.29 (0.17-0.51), safety-pad; OR 0.13 (0.06-0.27), p<0.001). And after 12 months, RS-RARP showed better results only in the safety-pad(0 pad; OR 0.64 (0.35-1.18), p = 0.15, safety-pad; OR 0.12 (0.04-0.36), p<0.001). In PSM, there was no statistical difference between two group at overall stage, but RS-RARP was observed to be higher than C-RARP in pT3 subgroup analysis(OR 0.74 (0.55-0.99), p = 0.047) (Fig 1). Whereas, there was no significant difference between the two groups in complication, operation time, and EBL. CONCLUSIONS: Our analysis showed that RS-RARP is superior about early continence recovery than C-RARP. However, RS-RARP showed relatively high PSM in locally advanced PCa of pT3 or above. Therefore, although RS-RARP has few advantages about functional outcomes, we think that caution should be exercised when approaching patients with high-risk local diseases.

Effect of neoadjuvant chemotherapy on overall survival of patients with T2-4aN0M0 bladder cancer: A systematic review and meta-analysis according to EAU COVID-19 recommendation.

PURPOSE: In the context of the COVID-19 outbreak, the European Association of Urology (EAU) guidelines Rapid Reaction Group provided recommendations to manage muscle invasive bladder cancer (MIBC) based on priority levels: neoadjuvant chemotherapy (NAC) should be avoided for patients with T2-3N0M0 MIBC. This meta-analysis aims to evaluate the efficacy of NAC compared with radical cystectomy (RC) alone in improving the overall survival (OS) of patients with T2-4aN0M0 MIBC. MATERIALS AND METHODS: A systematic review was performed according to the PRISMA guidelines. The PubMed/Medline, EMBASE, and Cochrane Library databases were searched. The primary outcome was OS of patients with T2-4aN0M0 MIBC, and the secondary outcome was OS of patients with only T2N0M0 MIBC. RESULTS: Eight studies were included in this meta-analysis. Overall, the quality of all studies was relatively high, and little publication bias was demonstrated. The OS was significantly better in the NAC with RC group than in RC alone (HR, 0.79; 95% CI, 0.68-0.92; p = 0.002). A subgroup analysis was performed on only patients with T2N0M0 MIBC, and five studies were included. There was no difference in the OS between the NAC with RC and the RC alone groups (HR, 0.83; 95% CI, 0.69-1.01 p = 0.06). CONCLUSIONS: As recommended by the EAU guidelines Rapid Reaction Group, patients with T2N0M0 MIBC should strongly consider omitting NAC until the end of the COVID-19 pandemic. Whether to omit NAC in T3-4aN0M0 MIBC needs further discussion, and studies targeting only T2-3N0M0 MIBC are expected to proceed further.

Antibiotic prophylaxis for percutaneous nephrolithotomy: An updated systematic review and meta-analysis.

INTRODUCTION: A single dose of preventive antibiotics is known to be sufficient to reduce the rate of infection-related complications in percutaneous nephrolithotomy (PCNL). However, some studies reported that the extended dose showed lower complications for high-risk groups. Therefore, we performed a systematic review and meta-analysis comparing single- and extended-dose antibiotic prophylaxis for PCNL. MATERIALS AND METHODS: Relevant studies that compared single- and extended-dose antibiotic prophylactic therapies were identified. Articles were selected from PubMed, EMBASE, KoreaMed, and Google Scholar up to September 2021. Fever and systemic inflammatory response syndrome (SIRS) were compared by meta-analysis. A subgroup analysis was performed according to the degree of risk to the patient. RESULTS: A total of 10 articles were included in this study. There were no significant differences between single dose and extended dose in the rate of fever [p = 0.93, OR = 0.96, 95% confidence interval (CI) 0.44-2.13, I2 = 64%]. Extended dose showed lower rate of SIRS compared to single dose (p = 0.0005, OR = 1.81, 95% CI 1.30-2.53, I2 = 53%); in the subgroup analysis, extended dose also showed lower rates of SIRS compared to single dose in high-risk patients (p <0.0001, OR = 3.53, 95% CI 1.91-6.54, I2 = 36%). CONCLUSIONS: The results of our meta-analysis showed that single-dose antibiotic prophylaxis can be effective for PCNL, but extended-dose antibiotics can be required in high-risk patients to reduce post-PCNL infection-related complications.

Comparison of Ultra-Mini Percutaneous Nephrolithotomy and Retrograde Intrarenal Surgery for Renal Stones: A Systematic Review and Meta-Analysis from the KSER Update Series.

Miniaturized percutaneous nephrolithotomy (PCNL) and retrograde intrarenal surgery (RIRS) for renal stones have been developed to overcome the invasive disadvantages of PCNL. We aimed to compare the therapeutic effect and safety of ultra-mini percutaneous nephrolithotomy (UMPCNL) and RIRS for renal stones using an updated systematic review and meta-analysis. We searched clinical trials comparing UMPCNL and RIRS for renal stones using the PubMed, EMBASE, Cochrane Library, and Google Scholar databases up to October 2021. Seven studies were included in the current study. The renal stone size was 10-20 mm in three studies, 10-25 mm in one study, 10-35 mm in two studies, and not specified in one study. The stone-free rate of UMPCNL was higher than that of RIRS (p = 0.02; odds ratio (OR) = 2.01; 95% confidence interval (CI) = 1.12, 3.61). The complication rate showed no significant difference between UMPCNL and RIRS (p = 0.48; OR = 1.20; 95% CI = 0.73, 1.98). Regarding the operative time, UMPCNL was shorter than RIRS (p = 0.005; weighted mean difference (WMD) = -15.63; 95% CI = -26.60, -4.67). The hospital stay of UMPCNL was longer than that of RIRS (p = 0.0004; WMD = 1.48; 95% CI = 0.66, 2.31). UMPCNL showed higher efficacy than RIRS and similar safety to RIRS. UMPCNL may be a useful therapeutic option for moderate-sized renal stones.

Novel Treatment Strategy Using Second-Generation Androgen Receptor Inhibitors for Non-Metastatic Castration-Resistant Prostate Cancer.

Non-metastatic castration-resistant prostate cancer (nmCRPC) is defined by a progressively rising prostate-specific antigen level, despite a castrate level of testosterone, in the absence of obvious radiologic evidence of metastatic disease on conventional imaging modalities. As a significant proportion of patients with nmCRPC develop metastatic diseases, the therapeutic goals of physicians for these patients are to delay metastasis development, preserve quality of life, and increase overall survival (OS). Since 2018, the treatment of nmCRPC has changed dramatically with the introduction of second-generation androgen receptor inhibitors, such as enzalutamide (ENZA), apalutamide (APA), and darolutamide (DARO). These drugs demonstrated substantial improvements in metastasis-free survival (MFS) and OS in phase III randomized clinical trials. In addition, these drugs have an excellent safety profile, preserve quality of life, and can delay disease-related symptoms. A recently published indirect meta-analysis reported that APA and ENZA showed better findings in MFS and that DARO had relatively fewer adverse effects. However, in the absence of a direct comparison, careful interpretation is required. Thus, APA, ENZA, and DARO should be considered the new standard drugs for treating nmCRPC.

Comparison of Oncologic Outcomes of Dose-Dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin (ddMVAC) with Gemcitabine and Cisplatin (GC) as Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer: Systematic Review and Meta-Analysis.

Platinum-based neoadjuvant chemotherapy (NAC) is widely used for treating muscle-invasive bladder cancer (MIBC). A systematic review was performed following PRISMA guidelines. PubMed, Embase, and the Cochrane Library were searched up to December 2020. We conducted a meta-analysis to compare the oncologic outcomes of ddMVAC (dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin) and GC (gemcitabine and cisplatin), which are the most widely used NAC regimens. Endpoints included pathologic complete response (pCR), pathologic downstaging (pDS), overall survival (OS), and cancer-specific survival (CSS). Five studies, with a total of 1206 patients, were included for meta-analysis. pCR was observed in 35.2% of the ddMVAC arm and in 25.1% of the GC arm, and pCR was significantly higher in ddMVAC than in GC (odds ratio (OR), 1.45; 95% confidence interval (CI), 1.11-1.89; p = 0.006). There was no significant difference in pDS (OR, 1.37; CI, 0.84-2.21; p = 0.20). OS was significantly higher in ddMVAC than in GC (hazard ratio, 2.16; CI, 1.42-3.29; p = 0.0004). Only one study reported CSS outcomes. The results of this analysis indicate that ddMVAC is superior to GC in terms of pCR and OS, suggesting that ddMVAC is more effective than GC in NAC for MIBC. However, this should be interpreted with caution because of the inherent limitations of retrospective studies.

Three-Dimensional Reconstruction of Neurovascular Network in Whole Mount Preparations and Thick-Cut Transverse Sections of Mouse Urinary Bladder.

PURPOSE: Proper functional and structural integrity of nervous and vascular system in urinary bladder plays an important role in normal bladder function and the disruption of these structures is known to be related to lower urinary tract symptoms. Here, we present an immunohistochemical staining method that delineates neurovascular structures in the mouse urinary bladder by using immunohistochemical staining with three-dimensional reconstruction. MATERIALS AND METHODS: The urinary bladder was harvested from 8-week-old C57BL/6 male mouse. Lamina propria and detrusor muscle layer were dissected for whole mount staining, and thick-cut (60-µm) sections were prepared for full-thickness bladder staining. Immunofluorescent staining of bladder tissue was performed with antibodies against CD31 (an endothelial cell marker), smooth muscle α-actin (a smooth muscle cell marker), NG2 (a pericyte marker), and ßIII-tubulin (a neuronal marker). We reconstructed three-dimensional images of bladder neurovascular system from stacks of two-dimensional images. RESULTS: Three-dimensional images obtained from thick-cut sections clearly provided good anatomic information about neurovascular structures in the three layers of bladder, such as urothelium, lamina propria, and detrusor muscle layer. Whole mount images of lamina propria and detrusor muscle layer also clearly delineated spatial relationship between nervous and vascular systems. The microvessel density was higher in the lamina propria than in the detrusor muscle layer. Nerve fibers were evenly innervated into the lamina propria and detrusor muscle. CONCLUSIONS: This study provides comprehensive insight into three-dimensional neurovascular structures of mouse urinary bladder. Our technique may constitute a standard tool to evaluate pathologic changes in a variety of urinary bladder diseases.

Neutralizing antibody to proNGF rescues erectile function by regulating the expression of neurotrophic and angiogenic factors in a mouse model of cavernous nerve injury.

BACKGROUND: Radical prostatectomy induces some degree of cavernous nerve injury (CNI) and causes denervation-induced pathologic changes in cavernous vasculature, regardless of the advances in surgical techniques and robotic procedures. The precursor for nerve growth factor (proNGF) is known to be involved in neuronal cell apoptosis and microvascular dysfunction through its receptor p75NTR . OBJECTIVES: To determine the expression of proNGF/p75NTR and the efficacy of proNGF neutralizing antibody (anti-proNGF-Ab) in a mouse model of ED induced by CNI. MATERIALS AND METHODS: Age-matched 12-week-old C57BL/6 mice were distributed into three groups: sham group and bilateral CNI group treated with intracavernous injections of PBS (20 µL) or of anti-proNGF-Ab (20 µg in 20 µL of PBS) on days -3 and 0. Two weeks after treatment, erectile function was measured by electrical stimulation of cavernous nerve. Penis tissues from a separate group of animals were harvested for further analysis. We also determined the efficacy of anti-proNGF-Ab on neural preservation in major pelvic ganglion (MPG) ex vivo. RESULTS: We observed increased penile expression of proNGF and p75NTR after CNI. Intracavernous administration of anti-proNGF-Ab increased nNOS and neurofilament expression probably by enhancing the production of neurotrophic factors, such as neurotrophin-3, NGF, and brain-derived neurotrophic factor. Anti-proNGF-Ab preserved the integrity of cavernous sinusoids, such as pericytes, endothelial cells, and endothelial cell-to-cell junctions, possibly by controlling angiogenic factors (angiopoietin-1, angiopoietin-2, and vascular endothelial growth factor) and induced endogenous eNOS phosphorylation in CNI mice. And finally, treatment with anti-proNGF-Ab rescued erectile function in CNI mice. Anti-proNGF-Ab also enhanced neurite sprouting from MPG exposed to lipopolysaccharide. DISCUSSION AND CONCLUSION: The preservation of damaged cavernous neurovasculature through inhibition of the proNGF/p75NTR pathway may be a novel strategy to treat radical prostatectomy-induced erectile dysfunction.

Visceral Adiposity as a Significant Predictor of Sunitinib-Induced Dose-Limiting Toxicities and Survival in Patients with Metastatic Clear Cell Renal Cell Carcinoma.

Sunitinib is a first-line treatment for metastatic renal cell carcinoma (mRCC). Little is known about the predictive factors of sunitinib-induced dose-limiting toxicity (DLT) in Asian populations. We investigated whether body composition predicts sunitinib-induced DLT. We retrospectively reviewed sunitinib-treated Korean patients with clear cell mRCC from eight institutions. Body composition was measured using computed tomography. DLT was defined as any adverse event leading to dose reduction or treatment discontinuation. Univariate analysis was used to compare body composition indices, and logistic regression analyses were performed for factors predicting early DLT. Overall, 111/311 (32.5%) of patients experienced DLT. Significant differences were observed in the subcutaneous adipose tissue index (SATI; p = 0.001) and visceral adipose tissue index (VATI; p < 0.001) between patients with and without DLT. Multivariate analyses revealed that VATI (odds ratio: 1.013; p = 0.029) was significantly associated with early DLT. Additionally, 20% of patients who had a body mass index (BMI) greater than 23 kg/m2 and a low VATI experienced DLT, whereas 34.3% of the remaining groups had DLT (p = 0.034). Significant differences were observed for median progression-free survival (13.0 vs. 26.0 months, respectively; p = 0.006) between patients with low and high VATI. Visceral adiposity was a significant predictor of sunitinib-associated DLT and survival. Patients with a low VATI and a BMI greater than 23 kg/m2 experienced lower DLTs.

Comparison of oncologic outcomes between partial nephrectomy and radical nephrectomy in patients who were upstaged from cT1 renal tumor to pT3a renal cell carcinoma: an updated systematic review and meta-analysis.

AIM: Owing to the limited ability of current imaging modalities, several clinical T1 renal cell carcinomas (cT1 RCCa) can be pathologically upstaged to T3a (pT3a) after surgery. There have been some controversies regarding the oncological safety of partial nephrectomy (PNx) compared with radical nephrectomy (RNx) in these patients. We compared oncological outcomes of PNx and RNx in patients with upstaged pT3a RCCa. METHODS: A systematic review was performed following the PRISMA guideline. PubMed, MEDLINE, Embase were searched. Oncological outcomes [recurrence-free survival (RFS), overall survival (OS) and cancer-specific survival (CSS)] between PNx and RNx were compared. The GRADE approach was used to rate the certainty of evidence. RESULTS: A total of 7406 patients in 12 articles related to upstaged pT3a RCCa were included. In adjusted analysis, no difference was observed in RFS [hazard ratios (HR) 0.87; 95% confidence intervals (CI), 0.57-0.95; p = 0.88] and CSS (HR, 0.78; 95% CI, 0.59-1.04; p = 0.09) for PNx and RNx. Meanwhile, PNx was significantly associated with favorable OS compared with RNx (HR, 0.74; 95% CI, 0.57-0.95; p = 0.02). CONCLUSIONS: Our meta-analysis shows that patients treated with PNx have better or at least similar oncological outcomes compared with RNx in patients with upstaged pT3a RCCa from cT1. In particular, patients who had undergone PNx show a significantly improved OS. If PNx is available, we recommend performing PNx for all cT1 RCCa, even in patients with upstaging potential. However, due to the low level of evidence, large-scale randomized trials are required.