Association of salivary testosterone levels during the post-awakening period with age and symptoms suggestive of late-onset hypogonadism in men.

BACKGROUND: The lack of association between serum testosterone levels and symptoms suggestive of hypogonadism is a significant barrier in the determination of late-onset hypogonadism (LOH) in men. This study explored whether testosterone levels increase after morning awakening, likewise the cortisol awakening response (CAR) in the hypothalamic-pituitary-adrenal (HPA) axis, and whether testosterone levels during the post-awakening period are associated with age and symptoms suggestive of late-onset hypogonadism (LOH) in men. METHODS: Testosterone and cortisol levels were determined in saliva samples collected immediately upon awakening and 30 and 60 min after awakening, and scores of the Aging Males' Symptoms (AMS) questionnaire were obtained from 225 healthy adult men. RESULTS: A typical CAR (an increase in cortisol level ≥ 2.5 nmol/L above individual baseline) was observed in 155 participants (the subgroup exhibiting typical CAR). In the subgroup exhibiting CAR, testosterone levels sharply increased during the post-awakening period, showing a significant negative correlation with age, total AMS score, and the scores of 11 items on the somatic, psychological, and sexual AMS subscales. Of these items, three sexual items (AMS items #15-17) were correlated with age. Meanwhile, there was no notable increase in testosterone levels and no significant correlation of testosterone levels with age and AMS score in the subgroup exhibiting no typical CAR (n = 70). CONCLUSIONS: The results indicate that the hypothalamus-pituitary-gonad (HPG) axis responds to morning awakening, and determining testosterone levels during the post-awakening period in men with typical CAR may be useful for assessing HPG axis function and LOH.

The present study found that the HPG axis in healthy adult men responds to the morning awakening, characterized by increased salivary testosterone levels after the awakening period.The levels of salivary testosterone during the first hour after awakening are negatively associated with age and the severity of symptoms suggestive of LOH in adult men with typical CAR.

Adjuvant chemotherapy after radical nephroureterectomy for upper tract urothelial carcinoma with variant histology: A systematic review and meta-analysis of survival outcomes.

INTRODUCTION: To determine effects of adjuvant chemotherapy (AC) on survival outcomes compared to surgery alone without AC for upper tract urothelial carcinoma (UTUC) patients with variant histology (VH). METHODS: We conducted a systematic review and meta-analysis of studies investigating AC for UTUC in Medline, Embase, the Cochrane library up to January 2023. Population, intervention, comparator, and outcome were UTUC patients with VH, radical nephroureterectomy with AC, radical nephroureterectomy only, and oncological survival, respectively. RESULTS: Four retrospective studies were included. Regarding overall survival (OS), the pooled hazard ratio was 0.61 (95% confidence interval: 0.42-0.87; p = 0.007) across two studies. Regarding cancer specific survival (CSS), the pooled hazard ratio was 0.46 (95% confidence interval: 0.25-0.84; p = 0.01) across three studies. All included studies had a high quality based on the Newcastle-Ottawa Scale. Certainty of evidence for OS was low. Certainty of evidence for CSS was moderate due to a strong association (hazard ratio < 0.5). Publication bias was not significant for any studies. CONCLUSION: In UTUC patients with VH, administration of AC after surgery might have better survival outcomes than surgery alone. Our study provides evidence for decision-making of clinicians who treat UTUC patients with VH.

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.

Differences in clinical features between focal and extensive types of cystitis glandularis in patients without a previous history of urinary tract malignancy.

PURPOSE: To understand the clinical differences of cystitis glandularis (CG), a proliferative disorder of urinary bladder epithelium, based on the extent of cystoscopic findings in patients without a history of urinary tract malignancy. MATERIALS AND METHODS: We conducted a review of patients diagnosed with CG in two tertiary hospitals from 2005 to 2021. Patients with previous or concurrent history of urinary tract malignancy were excluded. Medical records, including demographics, endoscopic and all available imaging studies, and managements, were reviewed. Patients were divided into two types according to extent of the lesion, and their clinical features were compared. RESULTS: In total, 110 patients were enrolled in the final analysis, with 36 (32.7%) classified as extensive type and 74 (67.3%) as focal type. Patients with extensive type were predominantly males and relatively younger than those with focal type (p=0.025). Voiding problems were more strongly associated and hydronephrosis caused by CG was significantly more common in the extensive type (p=0.005 and p=0.003, respectively). Multiple transurethral resection procedures were more frequently performed in the extensive type (p=0.017). Subsequent urinary tract malignancy was observed in four patients, all of whom had focal-type CG. CONCLUSIONS: There were significant differences in clinical features between the extensive- and focal-types CG. The extensive type was more often associated with urologic complications. Meanwhile, in the focal type, subsequent urinary tract malignancy might develop during the follow-up period. Thus, thorough initial work-up and careful follow-up is necessary despite the benign nature of CG. Annual surveillance cystoscopy may be appropriate.

Effects of resection volume on postoperative micturition symptoms and retreatment after transurethral resection of the prostate.

PURPOSE: Despite advances in technology, such as advent of laser enucleation and minimally invasive surgical therapies, transurethral resection of the prostate (TURP) remains the most widely performed surgical technique for benign prostatic hyperplasia (BPH). We evaluated resection volume (RV)-derived parameters and analyzed the effect of RV on post-TURP outcomes. METHODS: This observational study used data from patients who underwent TURP at two institutions between January 2011 and December 2021 Data from patients with previous BPH surgical treatment, incomplete data, and underlying disease affecting voiding function were excluded. The collected data included age, prostate-specific antigen, transrectal ultrasound (TRUS)- and uroflowmetry-derived parameters, RV, perioperative laboratory values, perioperative International Prostatic Symptom Score (IPSS), follow-up period, retreatment requirements and interval between the first TURP and retreatment. RESULTS: In 268 patients without prior BPH medication, there were no differences in prostate volume (PV), transitional zone volume (TZV), or RV according to IPSS. A total of 60 patients started retreatment, including medical or surgical treatment, within the follow-up period. There was a significant difference in RV/PV between the groups without and with retreatment respectively (0.56 and 0.37; p = 0.008). However, preoperative TRUS- and uroflowmetry-derived parameters did not differ between the two groups. Multiple linear regression analysis showed that RV (p = 0.003) and RV/TZV (p = 0.006) were significantly associated with differences in perioperative IPSS. In the multivariate logistic regression analysis, only RV/PV was correlated with retreatment (p = 0.010). CONCLUSION: Maximal TURP leads to improved postoperative outcomes and reduced retreatment rate, it may gradually become a requirement rather than an option.

Circulating Tumor DNA Analysis on Metastatic Prostate Cancer with Disease Progression.

The positivity rate of circulating tumor DNA (ctDNA) next-generation sequencing (NGS) varies among patients with metastatic prostate cancer (mPC), complicating its incorporation into regular practice. This retrospective study analyzed the ctDNA sequencing results of 100 mPC patients from May 2021 to March 2023 to identify the factors associated with positive ctDNA. Three custom gene panels were used for sequencing. Overall, 63% of the patients exhibited tier I/II somatic alterations, while 12% had pathogenic/likely pathogenic germline alterations. The key genes that were altered included AR, TP53, RB1, PTEN, and APC. Mutations in BRCA1/2, either germline or somatic, were observed in 21% of the patients. Among the metastatic castration-resistant prostate cancer (mCRPC) patients, the ctDNA-positive samples generally showed higher median prostate-specific antigen (PSA) levels and were more likely to be at the radiographic and clinical progressive disease stages, although they were not significantly associated with PSA progression. Our results suggest that ctDNA analysis could detect meaningful genetic changes in mPC patients, especially during disease progression.

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.

Impact of Preoperative Ureteral Stenting in Retrograde Intrarenal Surgery for Urolithiasis.

Background and Objectives: Ureteral stent insertion passively dilates the ureter. Therefore, it is sometimes used preoperatively before flexible ureterorenoscopy to make the ureter more accessible and facilitate urolithiasis passage, especially when ureteroscopic access has failed or when the ureter is expected to be tight. However, it may cause stent-related discomfort and complications. This study aimed to assess the effect of ureteral stenting prior to retrograde intrarenal surgery (RIRS). Materials and Methods: Data from patients who underwent unilateral RIRS for renal stone with the use of a ureteral access sheath from January 2016 to May 2019 were retrospectively analyzed. Patient characteristics, including age, sex, BMI, presence of hydronephrosis, and treated side, were recorded. Stone characteristics in terms of maximal stone length, modified Seoul National University Renal Stone Complexity score, and stone composition were evaluated. Surgical outcomes, including operative time, complication rate, and stone-free rate, were compared between two groups divided by whether preoperative stenting was performed. Results: Of the 260 patients enrolled in this study, 106 patients had no preoperative stenting (stentless group), and 154 patients had stenting (stenting group). Patient characteristics except for the presence of hydronephrosis and stone composition were not statistically different between the two groups. In surgical outcomes, the stone-free rate was not statistically different between the two groups (p = 0.901); however, the operation time for the stenting group was longer than that of the stentless group (44.8 ± 24.2 vs. 36.1 ± 17.6 min; p = 0.001). There were no differences in the complication rate between the two groups (p = 0.523). Conclusions: Among surgical outcomes for RIRS with a ureteral access sheath, preoperative ureteral stenting does not provide a significant advantage over non-stenting with respect to the stone-free rate and complication rate.

A New Parameter for Calcium Oxalate Stones: Impact of Linear Calculus Density on Non-Contrast Computed Tomography.

Background and Objectives: Non-contrast computed tomography (NCCT) is widely used to evaluate urolithiasis. The NCCT attenuation, measured in Hounsfield units (HU), has been evaluated to predict stone characteristics. We propose a novel parameter, linear calculus density (LCD), and analyze variables from NCCT imaging to predict calcium oxalate (CaOx) stones, which are common and challenging to fragment. Materials and Methods: We retrospectively reviewed the medical records of patients with urolithiasis between 2014 and 2017. Among those, 790 patients were included. Based on the NCCT pre-treatment, the maximal stone length (MSL), mean stone density (MSD), and stone heterogeneity index (SHI) were obtained. In addition, the variation coefficient of stone density (VCSD = SHI/MSD × 100) and linear calculus density (LCD = VCSD/MSL) were calculated. In accordance with the stone analysis, the patients were divided into two groups (CaOx and non-CaOx groups). The logistic regression model and receiver operating characteristic (ROC) curve were used for predictive modeling. Results: In the CaOx group, the SHI, VCSD, and LCD were more significant than in the non-CaOx group (all p < 0.001). SHI (OR 1.002, 95% CI 1.001-1.004, p < 0.001), VCSD (OR 1.028, 95% CI 1.016-1.041, p < 0.001), and LCD (OR 1.352, 95% CI 1.270-1.444, p < 0.001) were significant independent factors for CaOx stones in the logistic regression models. The areas under the ROC curve for predicting CaOx stones were 0.586 for SHI, 0.66 for VCSD, and 0.739 for LCD, with a cut-point of 2.25. Conclusions: LCD can be a useful new parameter to provide additional information to help discriminate CaOx stones before treatment.

Optimal planning target margin for prostate radiotherapy based on interfractional and intrafractional variability assessment during 1.5T MRI-guided radiotherapy.

Introduction: We analyzed daily pre-treatment- (PRE) and real-time motion monitoring- (MM) MRI scans of patients receiving definitive prostate radiotherapy (RT) with 1.5 T MRI guidance to assess interfractional and intrafractional variability of the prostate and suggest optimal planning target volume (PTV) margin. Materials and methods: Rigid registration between PRE-MRI and planning CT images based on the pelvic bone and prostate anatomy were performed. Interfractional setup margin (SM) and interobserver variability (IO) were assessed by comparing the centroid values of prostate contours delineated on PRE-MRIs. MM-MRIs were used for internal margin (IM) assessment, and PTV margin was calculated using the van Herk formula. Results: We delineated 400 prostate contours on PRE-MRI images. SM was 0.57 ± 0.42, 2.45 ± 1.98, and 2.28 ± 2.08 mm in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions, respectively, after bone localization and 0.76 ± 0.57, 1.89 ± 1.60, and 2.02 ± 1.79 mm in the LR, AP, and SI directions, respectively, after prostate localization. IO was 1.06 ± 0.58, 2.32 ± 1.08, and 3.30 ± 1.85 mm in the LR, AP, and SI directions, respectively, after bone localization and 1.11 ± 0.55, 2.13 ± 1.07, and 3.53 ± 1.65 mm in the LR, AP, and SI directions, respectively, after prostate localization. Average IM was 2.12 ± 0.86, 2.24 ± 1.07, and 2.84 ± 0.88 mm in the LR, AP, and SI directions, respectively. Calculated PTV margin was 2.21, 5.16, and 5.40 mm in the LR, AP, and SI directions, respectively. Conclusions: Movements in the SI direction were the largest source of variability in definitive prostate RT, and interobserver variability was a non-negligible source of margin. The optimal PTV margin should also consider the internal margin.

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.

Intravesical Recurrence after Radical Nephroureterectomy in Patients with Upper Tract Urothelial Carcinoma Is Associated with Flexible Diagnostic Ureteroscopy, but Not with Rigid Diagnostic Ureteroscopy.

(1) Background: We assessed the impact of diagnostic ureteroscopy (URS) on intravesical recurrence (IVR) following radical nephroureterectomy (RNU) for upper tract urothelial carcinoma according to the type of URS. (2) Methods: Data on 491 consecutive patients who underwent RNU at two institutions between 2016 and 2019 were retrospectively reviewed. The study population was classified according to the type of URS performed before RNU as follows: non-URS, rigid URS, and flexible URS. The study outcome was IVR occurring within 1 year of RNU. Univariable and multivariable Cox proportional hazards models were used to estimate the risk of IVR. (3) Results: Altogether, 396 patients were included for analysis. Rigid and flexible URS were performed in 178 (45%) and 111 (28%) patients, respectively, while 107 (27%) patients did not undergo URS. IVR was identified in 99 (25%) patients. Multivariable Cox regression analysis revealed that the flexible URS group was significantly associated with increased IVR, compared to the non-URS group (HR = 1.807, p = 0.0416). No significant difference in IVR was observed between the non-URS and rigid URS groups (HR = 1.301, p = 0.3388). (4) Conclusions: In patients with UTUC undergoing RNU, rigid URS may not increase the risk of IVR, whereas flexible URS appears to be associated with a higher risk of IVR.

Characteristics of BRCA2 Mutated Prostate Cancer at Presentation.

Genetic alterations of DNA repair genes, particularly BRCA2 in patients with prostate cancer, are associated with aggressive behavior of the disease. It has reached consensus that somatic and germline tests are necessary when treating advanced prostate cancer patients. Yet, it is unclear whether the mutations are associated with any presenting clinical features. We assessed the incidences and characteristics of BRCA2 mutated cancers by targeted sequencing in 126 sets of advanced prostate cancer tissue sequencing data. At the time of diagnosis, cT3/4, N1 and M1 stages were 107 (85%), 54 (43%) and 35 (28%) samples, respectively. BRCA2 alterations of clinical significance by AMP/ASCO/CAP criteria were found in 19 of 126 samples (15.1%). The BRCA2 mutated cancer did not differ in the distributions of TNM stage, Gleason grade group or histological subtype compared to BRCA2 wild-type cancers. Yet, they had higher tumor mutation burden, and higher frequency of ATM and BRCA1 mutations (44% vs. 10%, p = 0.002 and 21% vs. 4%, p = 0.018, respectively). Of the metastatic subgroup (M1, n = 34), mean PSA was significantly lower in BRCA2 mutated cancers than wild-type (p = 0.018). In the non-metastatic subgroup (M0, n = 64), PSA was not significantly different (p = 0.425). A similar trend was noted in multiple metastatic prostate cancer public datasets. We conclude that BRCA2 mutated metastatic prostate cancers may present in an advanced stage with relatively low PSA.

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.

Comparison of Surgical Outcomes between Single-Use and Reusable Flexible Ureteroscopes for Renal Stone Management: A Systematic Review and Meta-Analysis.

Background and Objectives: Disposable flexible ureteroscopes have been widely used because of their cost-effectiveness and higher sterility potential compared with reusable flexible ureteroscopes. This study aimed to compare the surgical outcomes and complication rates in patients who undergo reusable or disposable flexible ureteroscopic stone surgeries (fURS) for urinary stone disease. Materials and Methods: A systematic review and meta-analysis were conducted under the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. This systematic review was registered with PROSPERO (CRD42022331291). Clinical trials comparing reusable and disposable fURS for stone disease were found from PubMed, EMBASE, Cochrane Library, and the Web of Science up to March 2022. Participants were patients with upper urinary tract stones; the interventions were reusable or disposable fURS. Outcomes, including stone-free rate, operation time, length of hospital stay, and complication rate, were compared for analysis. Results: Overall, 111 studies were identified, but after removing duplicate studies, 75 studies remained. Thirty-two of these studies were excluded. Of the 43 screened studies, 11 met the eligibility criteria. There was no difference in the stone-free rate (SFR) between disposable and reusable fURS (p = 0.14; OR = 1.36; 95% CI, 0.9 to 2.04). For operation time, no difference was identified between reusable and disposable fURS groups (p = 0.12; MD = -5.31; 95% CI, -12.08 to 1.46). For hospital stay, there was also no difference between the two groups (p = 0.61; MD = -0.03; 95% CI, -0.17 to 0.10). There was no significant difference in complication rate between the two groups (p = 0.85; OR = 0.95; 95% CI, 0.56 to 1.61). Conclusions: There were no differences in the SFR, operation time, length of hospital stay, and complication rate between reusable and disposable fURS. Disposable fURS may be a comparable alternative to reusable fURS.

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.

Relationship between Androgen Deprivation Therapy and Normal-Tension Glaucoma in Patients with Prostate Cancer: A Nationwide Cohort Study.

PURPOSE: This study assessed the relationship between newly developed normal-tension glaucoma (NTG) and androgen deprivation therapy (ADT) in patients with prostate cancer. MATERIALS AND METHODS: A retrospective population-based cohort study was performed. During the period between 2008 and 2017, a total of 218203 prostate cancer patients were identified in a nationwide claims database in the Republic of Korea. The final analysis included 170874 patients (42909 in the ADT group, 127965 in the control group) after applying the inclusion and exclusion criteria. The incidences of NTG according to ADT duration were compared with controls. Exact matching was conducted to adjust comorbidities between cohorts. Cox proportional hazard regression models were performed after controlling for latent confounding factors, and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the incidence of NTG according to ADT were obtained. RESULTS: In the matched cohort, the ADT group was associated with a significantly reduced risk of NTG in multivariable analysis compared to the control group. The risk of NTG decreased in patients who underwent ADT for less than 2 years (HR=0.824; 95% CI, 0.682-0.995; p=0.0440) and in those using ADT over 2 years (HR=0.796; 95% CI, 0.678-0.934; p=0.0051), compared to the controls. CONCLUSION: Medical castrations for patients with prostate cancer results in a lower incidence of newly diagnosed NTG compared to no ADT. These findings suggest that testosterone may be involved in the pathogenesis of NTG.

The Delivery of the Recombinant Protein Cocktail Identified by Stem Cell-Derived Secretome Analysis Accelerates Kidney Repair After Renal Ischemia-Reperfusion Injury.

Recent advances in cell therapy have shown the potential to treat kidney diseases. As the treatment effects of the cell therapies are mainly attributed to secretomes released from the transplanted cells, the delivery of secretomes or conditioned medium (CM) has emerged as a promising treatment option for kidney disease. We previously demonstrated that the controlled delivery of human placental stem cells (hPSC)-derived CM using platelet-rich plasma (PRP) ameliorated renal damages and restored kidney function in an acute kidney injury (AKI) model in rats. The proteomics study of the hPSC-CM revealed that hPSC secrets several proteins that contribute to kidney tissue repair. Based on our results, this study proposed that the proteins expressed in the hPSC-CM and effective for kidney repair could be used as a recombinant protein cocktail to treat kidney diseases as an alternative to CM. In this study, we analyzed the secretome profile of hPSC-CM and identified five proteins (follistatin, uPAR, ANGPLT4, HGF, VEGF) that promote kidney repair. We investigated the feasibility of delivering the recombinant protein cocktail to improve structural and functional recovery after AKI. The pro-proliferative and anti-apoptotic effects of the protein cocktail on renal cells are demonstrated in vitro and in vivo. The intrarenal delivery of these proteins with PRP ameliorates the renal tubular damage and improved renal function in the AKI-induced rats, yielding similar therapeutic effects compared to the CM delivery. These results indicate that our strategy may provide a therapeutic solution to many challenges associated with kidney repair resulting from the lack of suitable off-the-shelf regenerative medicine products.

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.