The efficacy of second-line tyrosine kinase inhibitor for patients with metastatic non-clear cell renal cell carcinoma following first-line immune-oncology combination therapy.

PURPOSE: Metastatic non-clear cell renal cell carcinoma (nccRCC) is a heterogeneous disease with a poor prognosis and is treated with immunotherapy (IO)-based combinations according to the clear cell renal cell carcinoma. Tyrosine-kinase inhibitors (TKIs), such as cabozantinib and axitinib, are commonly used as the 2nd line therapy after 1st line IO combination therapy, but their efficacy as 2nd line TKI therapy for nccRCC is unknown. In this study, we performed a retrospective multicenter analysis of nccRCC patients who were previously treated with IO combination therapy and received 2nd line TKIs. METHODS: Among 254 patients enrolled in the Japanese multicenter retrospective study, 52 patients with nccRCC histology who received second-line TKIs were included in this study. Progression-free survival and overall survival (OS) from 2nd line TKIs were analyzed by log-rank test and Cox-proportional hazard model. Objective response rate (ORR) of 2nd line TKIs were analyzed. RESULTS: The 1-year PFS and OS rates were 25.0% (95% CI = 13.1-36.8) and 63.8% (95% CI, 48.0-75.9), respectively. No patients had a complete response, 11 had a partial response, and 18 had stable disease. ORR was 21.1%. IMDC poor risk and sunitinib as the 2nd line therapy were significantly associated with poor PFS. CONCLUSION: The 2nd-line TKI was effective for a small group of nccRCC patients previously treated with IO combination therapy, although this study was retrospectively analyzed with a small number of cases.

Prevalence and risk factors for overactive bladder symptoms in patients with artificial urinary sphincter.

To demonstrate the prevalence and risk factors for overactive bladder symptoms associated with artificial urinary sphincter implantation, we investigated the patients who underwent primary artificial urinary sphincter implantation with severe urinary stress incontinence. Forty-eight patients who completely answered the questionnaires of the overactive bladder symptom score before surgery were included. Patient characteristics, urinary status at pre and 1, 3, 6, and 12 months post-device activation, and predictive factors for overactive bladder symptoms were examined. Sixty percent of the patients had preoperative overactive bladder symptoms. Until 12 months after device activation, 35-40% of all patients had overactive bladder symptoms. The rate of persistent and de novo postoperative overactive bladder symptoms was 44.8% and 26.3%, respectively. Daily pad use was not different between patients w/wo overactive bladder symptoms. The only risk factor for postoperative overactive bladder symptoms was a max cystometoric capacity < 200 mL measured by a preoperative urodynamic study. Attention must be given to both persistent and de novo overactive bladder symptoms associated with artificial urinary sphincter implantation for patients with stress incontinence. Counsel should equally be provided for preoperative overactive bladder symptoms, especially in cases with a cystometric capacity < 200 mL.

Trifecta outcomes of robotic partial nephrectomy in obese patients: A comparison of body mass index <25, 25 to <30, and ≥30.

OBJECTIVE: We analyzed robotic partial nephrectomy (RPN) outcomes in obese patients based on body mass index (BMI) and trifecta achievement. METHODS: We retrospectively reviewed 296 patients who underwent RPN at Kansai Medical University Hospital between 2014 and 2022. The preoperative clinical data and perioperative outcomes were evaluated. Trifecta achievement (negative surgical margin, no major complications, and no acute kidney injury on postoperative day three) and its relationship to three BMI groups (<25, 25 to <30, and ≥30) were the primary outcome. The correlation between factors in achieving trifecta and BMI was evaluated. Univariate and multivariate analyses assessed variables for achieving the trifecta with logistic regression analysis. C-statistics quantitatively evaluated the prediction accuracy. RESULTS: Among 296 patients, 264 (89.2%) achieved trifecta (BMI categories were <25 [89.9%], 25 to <30 [89.4%], and ≥30 [82.6%]). There was no significant BMI-related difference (p = 0.566). Intraoperative blood loss increased with the BMI (p = 0.034). Multivariate analyses showed preoperative aspects and dimensions used for anatomic (PADUA) score independently predicted trifecta failure (odds ratio 1.71; 95% confidence interval 1.32-2.20; p < 0.001). The C-statistics of the PADUA score increased with increasing BMI. CONCLUSIONS: Higher BMI patients had more intraoperative blood loss during RPN. However, RPN remains safe and has acceptable quality and functional outcomes. Since patients with high PADUA scores combined with a high BMI may be at risk of trifecta failure, this should be explained before RPN.

Diagnostic performance of photodynamic diagnosis with oral 5-aminolevulinic acid for upper tract- and bladder urothelial carcinoma: a single-centre, retrospective analysis.

PURPOSE: To compare the diagnostic performance of photodynamic diagnosis (PDD) enhanced with oral 5-aminolaevulinic acid between the suspected upper tract urothelial carcinoma (UTUC) and bladder urothelial carcinoma (BUC) cases. METHODS: This retrospective study included 18 patients with suspected UTUC who underwent ureteroscopy (URS) with oral 5-ALA in the PDD-URS cohort between June 2018 and January 2019; and 110 patients with suspected BUC who underwent transurethral resection of bladder tumour (TURBT) in the PDD-TURBT cohort between January 2019 and March 2023. Sixty-three and 708 biopsy samples were collected during diagnostic URS and TURBT, respectively. The diagnostic accuracy of white light (WL) and PDD in the two cohorts was evaluated, and false PDD-positive samples were pathologically re-evaluated. RESULTS: The area under the receiver operating characteristic curve (AUC) of PDD was significantly superior to that of WL in both cohorts. The per biopsy sensitivity, specificity, and positive and negative predictive values of PDD in patients in the PDD-URS and PDD-TURBT cohorts were 91.2 vs. 71.4, 75.9 vs. 75.3, 81.6 vs. 66.3, and 88.0 vs. 79.4%, respectively. The PDD-URS cohort exhibited a higher AUC than did the PDD-TURBT cohort (0.84 vs. 0.73). Seven of four false PDD-positive samples (57.1%) in the PDD-URS cohort showed potential precancerous findings compared with eight of 101 (7.9%) in the PDD-TURBT cohort. CONCLUSION: The diagnostic performance of PDD in the PDD-URS cohort was at least equivalent to that in the PDD-TURBT cohort.

Comparison of Cabozantinib and Axitinib as Second-line Therapy After Nivolumab Plus Ipilimumab in Patients With Metastatic Clear Cell Renal Cell Carcinoma: A Comparative Analysis of Retrospective Real-world Data.

BACKGROUND: To date, no studies have compared the treatment outcomes of second-line therapies in patients with metastatic clear cell renal cell carcinoma (ccRCC). This study retrospectively evaluated the efficacy of cabozantinib and axitinib as second-line treatments in patients with metastatic ccRCC who previously received immune-oncology combination therapy. PATIENTS AND METHODS: Patients with metastatic ccRCC treated with cabozantinib and axitinib as second-line therapy after nivolumab-ipilimumab treatment were identified among 243 patients with RCC treated between August 1, 2018 and January 31, 2022 at 34 institutions belonging to the Japanese Urological Oncology Group. Patients were assessed for treatment outcomes, including progression-free survival (PFS), overall survival, objective response rate (ORR), and incidence rate of treatment-related adverse events (AEs). RESULTS: Forty-eight patients treated with cabozantinib and 60 treated with axitinib as second-line therapy after nivolumab-ipilimumab treatment for metastatic ccRCC were identified. The median PFS (95% confidence interval) was 11.0 months (9.0-16.0) with cabozantinib and 9.5 months (6.0-13.0) with axitinib. The ORRs were 37.5% (cabozantinib) and 38.3% (axitinib). The rates of any-grade AEs and grade ≥3 AEs were 79.2% (cabozantinib) versus 63.3% (axitinib; P = .091) and 35.4% (cabozantinib) versus 23.3% (axitinib; P = .202), respectively. In the poor-risk group, PFS was longer in the cabozantinib group than in the axitinib group (P = .033). CONCLUSION: The efficacy and safety of cabozantinib and axitinib were comparable. In the poor-risk group, cabozantinib was more effective than axitinib. These findings provide valuable insights into the selection of second-line treatment options after nivolumab-ipilimumab treatment in patients with metastatic ccRCC.

Technical Aspects and Clinical Limitations of Sperm DNA Fragmentation Testing in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations.

PURPOSE: Sperm DNA fragmentation (SDF) is a functional sperm abnormality that can impact reproductive potential, for which four assays have been described in the recently published sixth edition of the WHO laboratory manual for the examination and processing of human semen. The purpose of this study was to examine the global practices related to the use of SDF assays and investigate the barriers and limitations that clinicians face in incorporating these tests into their practice. MATERIALS AND METHODS: Clinicians managing male infertility were invited to complete an online survey on practices related to SDF diagnostic and treatment approaches. Their responses related to the technical aspects of SDF testing, current professional society guidelines, and the literature were used to generate expert recommendations via the Delphi method. Finally, challenges related to SDF that the clinicians encounter in their daily practice were captured. RESULTS: The survey was completed by 436 reproductive clinicians. Overall, terminal deoxynucleotidyl transferase deoxyuridine triphosphate Nick-End Labeling (TUNEL) is the most commonly used assay chosen by 28.6%, followed by the sperm chromatin structure assay (24.1%), and the sperm chromatin dispersion (19.1%). The choice of the assay was largely influenced by availability (70% of respondents). A threshold of 30% was the most selected cut-off value for elevated SDF by 33.7% of clinicians. Of respondents, 53.6% recommend SDF testing after 3 to 5 days of abstinence. Although 75.3% believe SDF testing can provide an explanation for many unknown causes of infertility, the main limiting factors selected by respondents are a lack of professional society guideline recommendations (62.7%) and an absence of globally accepted references for SDF interpretation (50.3%). CONCLUSIONS: This study represents the largest global survey on the technical aspects of SDF testing as well as the barriers encountered by clinicians. Unified global recommendations regarding clinician implementation and standard laboratory interpretation of SDF testing are crucial.

Controversy and Consensus on Indications for Sperm DNA Fragmentation Testing in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations.

PURPOSE: Sperm DNA fragmentation (SDF) testing was recently added to the sixth edition of the World Health Organization laboratory manual for the examination and processing of human semen. Many conditions and risk factors have been associated with elevated SDF; therefore, it is important to identify the population of infertile men who might benefit from this test. The purpose of this study was to investigate global practices related to indications for SDF testing, compare the relevant professional society guideline recommendations, and provide expert recommendations. MATERIALS AND METHODS: Clinicians managing male infertility were invited to take part in a global online survey on SDF clinical practices. This was conducted following the CHERRIES checklist criteria. The responses were compared to professional society guideline recommendations related to SDF and the appropriate available evidence. Expert recommendations on indications for SDF testing were then formulated, and the Delphi method was used to reach consensus. RESULTS: The survey was completed by 436 experts from 55 countries. Almost 75% of respondents test for SDF in all or some men with unexplained or idiopathic infertility, 39% order it routinely in the work-up of recurrent pregnancy loss (RPL), and 62.2% investigate SDF in smokers. While 47% of reproductive urologists test SDF to support the decision for varicocele repair surgery when conventional semen parameters are normal, significantly fewer general urologists (23%; p=0.008) do the same. Nearly 70% would assess SDF before assisted reproductive technologies (ART), either always or for certain conditions. Recurrent ART failure is a common indication for SDF testing. Very few society recommendations were found regarding SDF testing. CONCLUSIONS: This article presents the largest global survey on the indications for SDF testing in infertile men, and demonstrates diverse practices. Furthermore, it highlights the paucity of professional society guideline recommendations. Expert recommendations are proposed to help guide clinicians.

Evaluation of sexual function after dutasteride treatment in patients with once-negative prostate biopsy and benign prostate hyperplasia.

INTRODUCTION: Patients with benign prostatic hyperplasia are usually treated with 5α-reduced inhibitors (5ARIs) such as finasteride and dutasteride. However, studies on the influence of 5ARIs on sexual function have been controversial. In this study, we evaluated the impact of dutasteride treatment for erectile function in patients with once-negative prostate biopsy and benign prostate hyperplasia. PATIENTS AND METHODS: 81 patients with benign prostate hyperplasia were enrolled in a one-armed prospective study. They were administrated 0.5 mg/day of dutasteride for 12 months. Patient characteristics and changes of International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF)-15 scores at baseline and 12 months after dutasteride administration were examined. RESULTS: The mean ± standard deviation (SD) age of the patients was 69.4 ± 4.9 years and the prostate volume was 56.6 ± 21.3 mL, respectively. The mean ± SD prostate volume and PSA levels were decreased 25.0 and 50.9%, respectively, after 12 months of dutasteride administration. IPSS total, voiding subscore, storage subscore, and quality of life score significantly improved after 12 months of dutasteride administration. No statistically significant change in IIEF-total score from 16.3 ± 13.5 to 18.8 ± 16.0 (p = 0.14), IIEF-EF score from 5.1 ± 6.9 to 6.4 ± 8.3 (p = 0.13) were observed. There was no decrease in erectile function severity. CONCLUSION: Twelve months administration of dutasteride for patients with BPH improved urinary function and did not increase the risk of sexual dysfunction.

Summary of the clinical practice manual for late-onset hypogonadism.

Testosterone plays an important role in maintaining both physical and mental function. Age-related testosterone depletion contributes to the development of angina, arteriosclerosis, obesity, metabolic syndrome, dementia, frailty, and a range of other conditions. A condition involving age-related testosterone depletion and the associated clinical symptoms is defined as late-onset hypogonadism (LOH). LOH is treated by testosterone replacement therapy. Indications for testosterone replacement therapy are determined by evaluating symptoms and signs.

[INSURANCE COVERAGE FOR INFERTILITY TREATMENT SINCE APRIL 2022: HOW MALE INFERTILITY TREATMENT HAS CHANGED IN INSURANCE MEDICAL INSTITUTION -FROM THE QUESTIONNAIRE FOR JAPAN SOCIETY FOR REPRODUCTIVE MEDICINE MALE INFERTILITY SPECIAL INTEREST GROUP (SIG)].

(Introduction) Beginning in April of 2022, infertility services-including assisted reproductive technologies and examinations and treatments for male infertility-were covered by health insurance in Japan. Although these changes are expected to bolster birth rates in Japan, increased numbers of patients and surgeries are anticipated, particularly following reductions in patient visits caused by COVID-19. (Materials and methods) We surveyed 13 members of the Male Infertility Special Interest Group of the Japanese Society for Reproductive Medicine using Microsoft Forms. Respondents were asked about the number of new male infertility patients and surgeries at their respective facilities before the COVID-19 pandemic, after the first wave, after the sixth wave, and after the insurance changes to cover treatments for male infertility. Respondents were also asked to describe challenges in meeting the demand created by these insurance coverage changes. (Results) Patients and surgeries (varicocelectomy and testicular sperm extraction) declined markedly after the first wave of COVID-19 but gradually recovered after the sixth wave. However, once male infertility-related services were covered by insurance in Japan, respondents observed a marked increase in new patients and surgeries compared to pre-COVID-19. The most frequently reported problem was that sperm cryopreservation was not covered by insurance. (Conclusions) This survey should be readministered after additional time has passed to capture longer-term changes following changes to insurance coverage in Japan. We anticipate the responses to the survey will reflect ongoing challenges associated with changes in insurance coverage for male infertility-related services.

Predictors of Curvature Improvement in Men With Peyronie's Disease Treated With Intralesional Collagenase Clostridium Histolyticum.

INTRODUCTION: Penile curvature is the most common abnormality that is observed by men with Peyronie's disease (PD). Collagenase Clostridium histolyticum (CCH) has become a standard treatment for PD patients. AIM: To identify predictor factors associated with improvements of penile curvature outcomes in men with PD treated with CCH. METHODS: We retrospectively collected the data of patients with PD treated with CCH up to 8 injections divided into 4 cycles between January 2014 and July 2020. Per protocol, penile curvature was assessed at baseline, and after the second and ford CCH cycle. If after cycle 2, curvature demonstrated no improvement, or penile curvature was significantly improved and the patient was happy, no further treatment was recommended. However, if penile curvature was significantly improved and the patient remained dissatisfied, 4 cycles were completed. Three categories of response were evaluated: improvement (≥10 degrees or ≥20%, either 1 happens), unchanged (±10 degrees or ±20%) or worsened (≥10 degrees or ≥20%, either 1 happens). Logistic regression analyses were performed to evaluate predictive factors associated with penile curvature improvements. OUTCOMES: Degrees of the curvature changes between the baseline and after the cycles of CCH. RESULTS: A total of 114 patients underwent CCH treatment. Median age was 57 years. Median PD duration was 11 months. At baseline, mean curvature was 47 degrees, 65% had dorsal curvature, 53% mid-shaft location, and 15% calcification. After CCH treatment, the mean final curvature was 40 degrees. A total of 44% improved the curvature, 39% had no change while 17% worsened after CCH treatment. Of men who had penile curvature improvement with CCH treatment, the mean curvature decreasing in degrees and percentage were 22 degrees and 41%, respectively. Men with baseline curvature ≤ 30, 31-59, and ≥ 60 degrees, the percentage curvature improvement were 29%, 43%, and 60%, respectively. Baseline curvature was the only significant predictor of penile curvature improvement after CCH (OR 1.33, 95% CI = 1.1, 1.7). CLINICAL IMPLICATIONS: We confirmed baseline penile curvature is the most important predictive factor, and this is the first report describing proportions of penile curvature improvement with CCH treatment. STRENGTHS AND LIMITATIONS: This study has several strengths, including the use of validated instruments. Nonetheless, there are limitations: the retrospective nature of the study, a single institution; and modelling device was not controlled. CONCLUSION: Penile curvature improvement was significantly more common in patients with greater baseline curvature, reaching up to 60% for patients with ≥ 60 degrees. Flores JM, Nascimento B, Punjani N, et al. Predictors of Curvature Improvement in Men With Peyronie's Disease Treated With Intralesional Collagenase Clostridium Histolyticum. J Sex Med 2022;19:1680-1686.

Establishment of a novel assessment of the quality of human spermatozoa measuring mitochondrial oxygen metabolism.

OBJECTIVE: We aimed to establish a novel sperm quality evaluation technology by measuring mitochondrial oxygen metabolism in human spermatozoa. RESULTS: Normozoospermic human sperm samples were used. After establishing the optimal parameters for measuring the oxygen metabolism of human sperm cells using the extracellular flux analyzer, we measured the oxygen consumption rate (OCR) of human spermatozoa exposed to different storage temperatures. Although sperm motility was significantly lower at 4 °C when compared with sperm motility at 37 °C, there were no significant differences in sperm vitality and the OCR under both conditions. The present study established a methodology for human sperm quality evaluation using extracellular flux analysis technology. The OCR evaluation could be a reliable measurement tool for assessing human sperm quality.

PBRM1 Immunohistochemical Expression Profile Correlates with Histomorphological Features and Endothelial Expression of Tumor Vasculature for Clear Cell Renal Cell Carcinoma.

Loss of the polybromo-1 (PBRM1) protein has been expected as a possible biomarker for clear cell renal cell carcinoma (ccRCC). There is little knowledge about how PBRM1 immunohistochemical expression correlates with the histomorphological features of ccRCC and the endothelial expression of tumor vasculature. The present study evaluates the association of architectural patterns with the PBRM1 expression of cancer cells using a cohort of 425 patients with nonmetastatic ccRCC. Furthermore, we separately assessed the PBRM1 expression of the endothelial cells and evaluated the correlation between the expression of cancer cells and endothelial cells. PBRM1 loss in cancer cells was observed in 148 (34.8%) patients. In the correlation analysis between architectural patterns and PBRM1 expression, macrocyst/microcystic, tubular/acinar, and compact/small nested were positively correlated with PBRM1 expression, whereas alveolar/large nested, thick trabecular/insular, papillary/pseudopapillary, solid sheets, and sarcomatoid/rhabdoid were negatively correlated with PBRM1 expression. PBRM1 expression in vascular endothelial cells correlated with the expression of cancer cells (correlation coefficient = 0.834, p < 0.001). PBRM1 loss in both cancer and endothelial cells was associated with a lower recurrence-free survival rate (p < 0.001). Our PBRM1 expression profile indicated that PBRM1 expression in both cancer and endothelial cells may be regulated in an orchestrated manner.

[A Case of Retroperitoneal Bronchogenic Cyst Diagnosed by Fluorescence in situ Hybridization].

A 50-year-old woman was referred to our hospital for consultation for a suspected left adrenal tumor detected by ultrasonography during a health check. Computed tomography and magnetic resonance imaging revealed a 4.7×3.4 cm tumor in the retroperitoneal space near the adrenal gland. The patient subsequently underwent laparoscopic tumor resection. Using fluorescence in situ hybridization (FISH), the resected tumor was diagnosed as a retroperitoneal bronchial cyst. Here we present a case of a definitive diagnosis of a retroperitoneal bronchial cyst using FISH, and review the cases of retroperitoneal bronchial cyst in the literature.

Antisperm Antibody Testing: A Comprehensive Review of Its Role in the Management of Immunological Male Infertility and Results of a Global Survey of Clinical Practices.

Antisperm antibodies (ASA), as a cause of male infertility, have been detected in infertile males as early as 1954. Multiple causes of ASA production have been identified, and they are due to an abnormal exposure of mature germ cells to the immune system. ASA testing (with mixed anti-globulin reaction, and immunobead binding test) was described in the WHO manual 5th edition and is most recently listed among the extended semen tests in the WHO manual 6th edition. The relationship between ASA and infertility is somewhat complex. The presence of sperm agglutination, while insufficient to diagnose immunological infertility, may indicate the presence of ASA. However, ASA can also be present in the absence of any sperm agglutination. The andrological management of ASA depends on the etiology and individual practices of clinicians. In this article, we provide a comprehensive review of the causes of ASA production, its role in immunological male infertility, clinical indications of ASA testing, and the available therapeutic options. We also provide the details of laboratory procedures for assessment of ASA together with important measures for quality control. Additionally, laboratory and clinical scenarios are presented to guide the reader in the management of ASA and immunological male infertility. Furthermore, we report the results of a recent worldwide survey, conducted to gather information about clinical practices in the management of immunological male infertility.

Sperm Vitality and Necrozoospermia: Diagnosis, Management, and Results of a Global Survey of Clinical Practice.

Sperm vitality testing is a basic semen examination that has been described in the World Health Organization (WHO) Laboratory Manual for the Examination and Processing of Human Semen from its primary edition, 40 years ago. Several methods can be used to test sperm vitality, such as the eosin-nigrosin (E-N) stain or the hypoosmotic swelling (HOS) test. In the 6th (2021) edition of the WHO Laboratory Manual, sperm vitality assessment is mainly recommended if the total motility is less than 40%. Hence, a motile spermatozoon is considered alive, however, in certain conditions an immotile spermatozoon can also be alive. Therefore, the differentiation between asthenozoospermia (pathological decrease in sperm motility) and necrozoospermia (pathological decrease in sperm vitality) is important in directing further investigation and management of infertile patients. The causes leading to necrozoospermia are diverse and can either be local or general, testicular or extra-testicular. The andrological management of necrozoospermia depends on its etiology. However, there is no standardized treatment available presently and practice varies among clinicians. In this study, we report the results of a global survey to understand current practices regarding the physician order of sperm vitality tests as well as the management practices for necrozoospermia. Laboratory and clinical scenarios are presented to guide the reader in the management of necrozoospermia with the overall objective of establishing a benchmark ranging from the diagnosis of necrozoospermia by sperm vitality testing to its clinical management.

Testosterone Therapy for Late-Onset Hypogonadism Improves Erectile Function: A Systematic Review and Meta-Analysis.

INTRODUCTION: Randomized controlled trials (RCTs) of testosterone therapy (TTh) for late-onset hypogonadism are systematically reviewed and a meta-analysis to assess the efficacy of TTh in improving erectile function is performed. METHODS: The PubMed, Cochrane Library, and Web of Science databases were searched to identify RCTs published from 2007. RCTs that assessed erectile function using the erectile function domain of the International Index of Erectile Function (IIEF-EFD) were included in the meta-analysis. RESULTS: The systematic review included 18 RCTs and the meta-analysis included 6 studies that enrolled a total of 1,458 patients. The overall meta-analysis revealed that the IIEF-EFD score was significantly improved in the TTh group compared with the placebo group (mean difference 1.86; 95% confidence interval 1.01-2.72; p < 0.0001). Compared with patients receiving placebo, there was a significant improvement in the IIEF-EFD of patients who received TTh using testosterone gel, those who received TTh for over 30 weeks, and those without diabetes mellitus or metabolic syndrome. CONCLUSION: TTh achieved a significant improvement in the IIEF-EFD score of hypogonadal men compared with placebo, especially in those who received testosterone gel, were treated for over 30 weeks, and had no comorbidities.

Tumor volume and tumor crossing of the axial renal midline predict renal function after robotic partial nephrectomy.

There are several nephrometry scoring systems for predicting surgical complexity and potential perioperative morbidity. The R.E.N.A.L. scoring system, one of the most well-known nephrometry scoring systems, emphasizes the features on which it is based (Radius, Exophytic/endophytic, Nearness to collecting system or sinus, Anterior/posterior, and Location relative to polar lines). The ability of these nephrometry scoring systems to predict loss of renal function after robotic partial nephrectomy (RPN) remains controversial. Therefore, we verified which combination of factors from nephrometry scoring systems, including tumor volume, was the most significant predictor of postoperative renal function. Patients who underwent RPN for cT1 renal tumors in our hospital were reviewed retrospectively (n = 163). The preoperative clinical data (estimated glomerular filtration rate [eGFR], comorbidities, and nephrometry scoring systems including R.E.N.A.L.) and perioperative outcomes were evaluated. We also calculated the tumor volume using the equation applied to an ellipsoid by three-dimensional computed tomography. The primary outcome was reduced eGFR, which was defined as an eGFR reduction of ≥ 20% from baseline to 6 months after RPN. Multivariable logistic regression analyses were used to evaluate the relationships between preoperative variables and reduced eGFR. Of 163 patients, 24 (14.7%) had reduced eGFR. Multivariable analyses indicated that tumor volume (cutoff value ≥ 14.11 cm3, indicating a sphere with a diameter ≥ approximately 3 cm) and tumor crossing of the axial renal midline were independent factors associated with a reduced eGFR (odds ratio [OR] 4.57; 95% confidence interval [CI] 1.69-12.30; P = 0.003 and OR 3.50; 95% CI 1.30-9.46; P = 0.034, respectively). Our classification system using these two factors showed a higher area under the receiver operating characteristic curve (AUC) than previous nephrometry scoring systems (AUC = 0.786 vs. 0.653-0.719), and it may provide preoperative information for counseling patients about renal function after RPN.

Integration of NRP1, RGS5, and FOXM1 expression, and tumour necrosis, as a postoperative prognostic classifier based on molecular subtypes of clear cell renal cell carcinoma.

Molecular mechanisms of progression of clear cell renal cell carcinoma (ccRCC) have been proven with recent genomic or transcriptional analyses. However, it is still difficult to apply these analyses to daily clinical practice owing to economical and practical issues. Here, we established a pathology-based, postoperative prognostic classification based on the well-validated transcriptional classifier, ClearCode34, in ccRCC. A total of 342 cases with available tissue were identified and randomly allocated into a discovery cohort (n = 138) and a validation cohort (n = 204). Levels of mRNA were quantified using a nCounter Digital Analyzer, and the ccA/ccB subtypes were determined. Histological and immunohistochemistry (IHC) analyses were subsequently performed to establish a pathology-based classification based on the mRNA levels. Finally, the prognostic ability of the new classifier was evaluated in both the discovery and validation cohorts. Of 138 cases in the discovery cohort, 78 (56.5%) and 60 (43.5%) were assigned to the ccA and ccB subtypes, respectively. Proangiogenic genes, neuropilin 1 (NRP1) and regulator of G protein signalling 5 (RGS5), were especially overexpressed in all ccRCC samples and were enriched in ccA-assigned tumours. Histologically, tumour necrosis and the sarcomatoid feature were associated with the ccB subtype. In IHC analyses, expression of NRP1, RGS5, and forkhead box M1 (FOXM1), an epithelial-mesenchymal transition-related factor, significantly correlated with the ccA/ccB subtypes. Combining these three IHC factors and tumour necrosis, we developed the IHC/histology-based classifier, which showed good concordance with the ClearCode34 classifier with an accuracy of 0.80. The established classification significantly stratified relapse-free, cancer-specific, and overall survival rates in both the discovery and validation cohorts. The novel molecular pathology classifier integrating NRP1, RGS5, FOXM1, and tumour necrosis may enable the stratification of oncological outcomes for patients with ccRCC undergoing resection surgery.

The Prevalence and Predictors of Penile Pain in Men with Peyronie's Disease.

INTRODUCTION: Penile pain is one of the most stressful symptoms in men with Peyronie's disease (PD). AIM: To evaluate the prevalence, clinical presentation and risk factors associated with penile pain in men with PD as well as to assess the psychosocial impact. METHODS: We revised our institution's database of men diagnosed with PD. The information collected included penile pain assessments, and the scores of the PD Questionnaire (PDQ), Self-Esteem and Relationship Questionnaire (SEAR) and Center for Epidemiologic Studies Depression Scale Questionnaire (CES-D). Descriptive and comparative statistics were used. Logistic regression analyses were performed to evaluate predictive factors associated with penile pain. MAIN OUTCOME MEASURES: Penile pain descriptive assessment and factors associated with penile pain in men with PD. Comparison of SEAR, CES-D and PDQ domain scores of men with and without penile pain. RESULTS: 431 men with PD were included for this analysis with a mean age of 55.9 years. Penile pain was reported by 36.7%; 65.2% of those had painful erection, 7% pain with flaccid state only, and 20% in both stages. The median pain severity was 3 with erection and 1 with flaccid stage. After adjusted logistic regression analyses, advanced age was associated with less pain (OR 0.94, P ≤ 0.001). Men with penile pain had no significant difference in CES-D and SEAR mean scores compared to men without penile pain. The PDQ scores for the physical/psychological symptoms domain and the bother domain were significantly higher in men with penile pain (12 vs 8.7; P < 0.01 and 9 vs 7.1; P < 0.01 respectively). Men with penile pain had a higher rate of clinically significant bother scores than men without penile pain (52% vs 35%, P ≤ 0.001). CONCLUSION: Penile pain is common in men with PD. It was more common in young men and was associated with physical and psychological bothers in this population. Flores JM, Salter CA, Nascimento B, et al. The Prevalence and Predictors of Penile Pain in Men with Peyronie's Disease. Sex Med 2021;9:100398.