Lower PHI, [-2]proPSA/fPSA and testosterone/estradiol ratios in healthy black men: preliminary results and potential implications in prostate cancer clinical management.

BACKGROUND: Black men residing in Western countries are more likely to develop prostate cancer (PCa), have higher mortality and are younger than the general population at initial diagnosis. In addition to genetic and environmental factors, the reasons for these racial disparities can also be attributed to social determinants of health such as low health literacy of this population and poor awareness of health services. Little is known about laboratory tests for PCa in black men. METHODS: In this preliminary study. we investigated whether ethnicity affect PSA molecular forms, PHI, estradiol and testosterone levels in healthy men. RESULTS: We found that healthy black men had lower PHI, [-2]proPSA/fPSA and testosterone/estradiol ratios. CONCLUSIONS: Our findings even if on a small study population could have a relevant clinical impact. since PCa screening is particularly relevant in black men who are at high risk of clinically significant PCa. PSA-based screening is needed and overdiagnosis must be avoided. Our findings could be particularly impactful. Future research on larger population needs to consider whether ethnicity specific laboratory tests thresholds could help to reduce the ethnic inequalities in prostate cancer diagnosis.

One out of two idiopathic infertile men has pathologic sperm DNA fragmentation values: Potential implications for clinical practice.

OBJECTIVES: To investigate the distribution of sperm DNA fragmentation (SDF) values and their association with clinical and seminal parameters in idiopathic infertile men. DESIGN, PATIENTS, MEASUREMENTS: Data from 3224 primary infertile men (belonging to couples having failed to conceive a pregnancy within 12 months) who underwent a thorough diagnostic work-up were analysed. A SDF value ≥ 30% (according to Sperm Chromatin Structure Assay) was considered pathologic. We excluded: (1) men with genetic abnormalities; (2) men with history of cryptorchidism; (3) men with biochemical hypogonadism; (4) men with clinical varicocele; and (5) men with other possible known aetiological factors. Descriptive statistics and logistic regression analyses were used to describe the whole cohort. RESULTS: Of all, 792 (23%) men with at least one abnormal WHO semen parameter but without any identified aetiologic factor for infertility, were considered as idiopathic infertile men. Of 792, 418 (52.7%) men had SDF ≥30%. Men with pathologic SDF were older (p = .02), had higher Follicle-stimulating hormone (FSH) (p = .04) but lower total testosterone (p = .03) values than those with SDF <30%. The homoeostatic model assessment index for insulin resistance (HOMA-IR) was higher in men with SDF ≥30% (p = .01). Idiopathic infertile men with SDF ≥30% presented with lower sperm concentration (p < .001) and lower progressive sperm motility (p < .01) than those with SDF < 30%. Logistic regression analysis revealed that older age (OR: 1.1, p = .02) and higher HOMA-IR score (OR: 1.8, p = .03) were associated with SDF ≥ 30%, after accounting for FSH and sperm concentration values. CONCLUSIONS: Approximately half of infertile men categorized as idiopathic had pathologic SDF values. Idiopathic infertile men with pathologic SDF showed worse clinical, hormonal and semen parameters than those with normal SDF values. These results suggest that including SDF testing could be clinically relevant over the real-life management work-up of infertile men.

Contemporary Diagnostic Work-Up for Male Infertility: Emphasizing Comprehensive Baseline Assessment.

Infertility is a prevalent issue affecting many couples during their reproductive years, with a significant number facing challenges in conceiving despite regular unprotected intercourse. Male factor infertility (MFI) contributes significantly to these cases, with a significant proportion of men lacking an identifiable etiology. As such, a thorough assessment of MFI has become increasingly vital for personalized management. This position paper from the Andrology team at IRCCS Ospedale San Raffaele emphasizes a comprehensive and individualized approach to MFI work-up, addressing the evolving challenges encountered in clinical practice. Our approach involves a thorough diagnostic work-up to identify the underlying causes of MFI, integrating insights from extensive literature review and our proprietary data. Our data demonstrates that an extensive diagnostic assessment allows us to identify at least one underlying cause of MFI in most infertile men. However, challenges persist in diagnosing less severe phenotypes with unclear etiology. We discuss the importance of individualized MFI work-up and its implications for developing rational therapeutic protocols. Lastly, this paper highlights the necessity for a personalized diagnostic assessment, addressing the daily clinical challenges and emphasizing tailored approaches to try to improve outcomes among couples seeking first medical help for infertility.

Role of Follicle-stimulating Hormone, Inhibin B, and Anti-Müllerian Hormone in Predicting Sperm Retrieval from Men with Nonobstructive Azoospermia Undergoing Microdissection Testicular Sperm Extraction: A Systematic Review and Meta-analysis.

Background and objective: No clear-cut markers for predicting positive sperm retrieval (+SR) at microdissection testicular sperm extraction (mTESE) have been identified thus far. Our aim was to conduct a systematic review and meta-analysis to evaluate the ability of follicle-stimulating hormone (FSH), inhibin B (InhB), and anti-Müllerian hormone (AMH) to predict +SR in men with nonobstructive azoospermia (NOA) undergoing mTESE. Methods: We performed a search in the PubMed, EMBASE, Web of Science, and Scopus databases according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Thirty-four publications were selected for inclusion in the analysis. Key findings and limitations: Overall, the mean +SR rate was 45%. Pooled standardized mean difference (SMD) values revealed significant hormonal differences between the +SR and -SR groups, with lower FSH (SMD -0.30), higher InhB (SMD 0.54), and lower AMH (SMD -0.56) levels in the +SR group. Pooled odds ratios (Ors) revealed no significant prediction of +SR by either FSH (OR 1.03, 95% confidence interval [CI] 1.00-1.06) or InhB (OR 1.01, 95% CI 1.00-1.02), despite variations in baseline levels and study heterogeneity. Conversely, AMH had significant predictive value (OR 0.82, 95% CI 0.73-0.92), with lower baseline levels in the +SR group. InhB and FSH levels were higher in the +SR group, while InhB exhibited the opposite trend. Conclusions and clinical implications: Despite study heterogeneity, our meta-analysis findings support the ability of AMH to predict +SR for men with NOA undergoing mTESE. Patient summary: We conducted a review and analysis of results from previous studies. Our findings show that for men with an infertility condition called nonobstructive azoospermia, blood levels of anti-Müllerian hormone can predict successful extraction of sperm using a microsurgical technique. Levels of two other hormones did not predict successful sperm extraction.

Oncological and Functional Outcomes of Penile Shaft Sparing Surgery for Localised Penile Cancer: A Systematic Review.

CONTEXT: Penile shaft sparing (PSS) surgery for localised penile cancer (PeCa) aims to balance oncological and functional outcomes. OBJECTIVE: To summarise the published evidence on different PSS approaches. EVIDENCE ACQUISITION: We performed a systematic review adhering to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The systematic search was performed on PubMed, EMBASE, and Scopus databases up to February 14, 2023. The inclusion criteria encompassed retrospective or prospective studies including patients ≥18 yr of age with localised PeCa treated with different PSS approaches, classified as laser ablation, circumcision, wide local excision, glansectomy with or without split skin graft, glans resurfacing, and mixed technique excision. The risk of bias was assessed using the Newcastle-Ottawa scale. A quantitative synthesis was not performed due to anticipated data heterogeneity and a lack of comparative studies. EVIDENCE SYNTHESIS: Out of 4343 articles identified, 47 met our inclusion criteria, including 10 847 patients. The year of publication ranged between 1983 and 2021. Nine studies were prospective case series, while the remaining studies were retrospective. No comparative studies were identified. Most of the cases included in these studies were Ta and T1. The oncological outcomes were good for all the approaches, with cancer-specific mortality ranging between 0% and 18%. Sexual and cosmetic outcomes, despite being under-reported, were good for all the approaches, with almost all patients being satisfied with their quality of life after surgery. The Newcastle and Ottawa scale revealed a high or severely high risk of bias in all the included studies. CONCLUSIONS: PSS approaches were safe and had good functional outcomes, considering however the overall low quality of the studies on this issue. PATIENT SUMMARY: The perioperative, function, and oncological outcomes of penile shaft sparing approaches are good. However, high-quality studies are needed to determine whether these approaches benefit patients with localised penile cancer.

Intraoperative image-guidance during robotic surgery: is there clinical evidence of enhanced patient outcomes?

BACKGROUND: To date, the benefit of image guidance during robot-assisted surgery (IGS) is an object of debate. The current study aims to address the quality of the contemporary body of literature concerning IGS in robotic surgery throughout different surgical specialties. METHODS: A systematic review of all English-language articles on IGS, from January 2013 to March 2023, was conducted using PubMed, Cochrane library's Central, EMBASE, MEDLINE, and Scopus databases. Comparative studies that tested performance of IGS vs control were included for the quantitative synthesis, which addressed outcomes analyzed in at least three studies: operative time, length of stay, blood loss, surgical margins, complications, number of nodal retrievals, metastatic nodes, ischemia time, and renal function loss. Bias-corrected ratio of means (ROM) and bias-corrected odds ratio (OR) compared continuous and dichotomous variables, respectively. Subgroup analyses according to guidance type (i.e., 3D virtual reality vs ultrasound vs near-infrared fluoresce) were performed. RESULTS: Twenty-nine studies, based on 11 surgical procedures of three specialties (general surgery, gynecology, urology), were included in the quantitative synthesis. IGS was associated with 12% reduction in length of stay (ROM 0.88; p = 0.03) and 13% reduction in blood loss (ROM 0.87; p = 0.03) but did not affect operative time (ROM 1.00; p = 0.9), or complications (OR 0.93; p = 0.4). IGS was associated with an estimated 44% increase in mean number of removed nodes (ROM 1.44; p < 0.001), and a significantly higher rate of metastatic nodal disease (OR 1.82; p < 0.001), as well as a significantly lower rate of positive surgical margins (OR 0.62; p < 0.001). In nephron sparing surgery, IGS significantly decreased renal function loss (ROM 0.37; p = 0.002). CONCLUSIONS: Robot-assisted surgery benefits from image guidance, especially in terms of pathologic outcomes, namely higher detection of metastatic nodes and lower surgical margins. Moreover, IGS enhances renal function preservation and lowers surgical blood loss.

Preoperative risk calculator for the probability of completing nephron sparing for kidney cancer.

PURPOSE: In absence of predictive models, preoperative estimation of the probability of completing partial (PN) relative to radical nephrectomy (RN) is invariably inaccurate and subjective. We aimed to develop an evidence-based model to assess objectively the probability of PN completion based on patients' characteristics, tumor's complexity, urologist expertise and surgical approach. DESIGN, SETTING AND PARTICIPANTS: 675 patients treated with PN or RN for cT1-2 cN0 cM0 renal mass by seven surgeons at one single experienced centre from 2000 to 2019. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSES: The outcome of the study was PN completion. We used a multivariable logistic regression (MVA) model to investigate predictors of PN completion. We used SPARE score to assess tumor complexity. We used a bootstrap validation to compute the model's predictive accuracy. We investigated the relationship between the outcomes and specific predictors of interest such as tumor's complexity, approach and experience. RESULTS: Of 675 patients, 360 (53%) were treated with PN vs. 315 (47%) with RN. Smaller tumors [Odds ratio (OR): 0.52, 95%CI 0.44-0.61; P < 0.001], lower SPARE score (OR: 0.67, 95%CI 0.47-0.94; P = 0.02), more experienced surgeons (OR: 1.01, 95%CI 1.00-1.02; P < 0.01), robotic (OR: 10; P < 0.001) and open (OR: 36; P < 0.001) compared to laparoscopic approach resulted associated with higher probability of PN completion. Predictive accuracy of the model was 0.94 (95% CI 0.93-0.95). CONCLUSIONS: The probability of PN completion can be preoperatively assessed, with optimal accuracy relaying on routinely available clinical information. The proposed model might be useful in preoperative decision-making, patient consensus, or during preoperative counselling. PATIENT SUMMARY: In patients with a renal mass the probability of completing a partial nephrectomy varies considerably and without a predictive model is invariably inaccurate and subjective. In this study we build-up a risk calculator based on easily available preoperative variables that can predict with optimal accuracy the probability of not removing the entire kidney.

Long-term functional outcomes in patients undergoing radical nephrectomy for renal cell carcinoma and tumor thrombus.

BACKGROUND: Up to 15% of patients with locally advanced renal cell carcinoma (RCC) harbors tumor thrombus (TT). In those cases, radical nephrectomy (RN) and thrombectomy represents the standard of care. We assessed the impact of TT on long-term functional and oncological outcomes in a large contemporary cohort. METHODS: Within a prospective maintained database, 1207 patients undergoing RN for non-metastatic RCC between 2000 and 2021 at a single tertiary centre were identified. Of these, 172 (14%) harbored TT. Multivariable logistic regression analyses evaluated the impact of TT on the risk of postoperative acute kidney injury (AKI). Multivariable Poisson regression analyses estimated the risk of long-term chronic kidney disease (CKD). Kaplan Meier plots estimated disease-free survival and cancer specific survival. Multivariable Cox regression models assessed the main predictors of clinical progression (CP) and cancer specific mortality (CSM). RESULTS: Patients with TT showed lower BMI (24 vs. 26 kg/m2) and preoperative Hb (11 vs. 14 g/mL; all-p < 0.05). Clinical tumor size was higher in patients with TT (9.6 vs. 6.5 cm; p < 0.001). After adjusting for potential confounders, the presence of TT was significantly associated with a higher risk of postoperative AKI (OR 2.03, 95% CI 1.49-3.6; p < 0.001) and long-term CKD (OR: 1.32, 95% CI 1.10-1.58; p < 0.01). Notably, patients with TT showed worse long-term oncological outcomes and TT was a predictor for CP (2.02, CI 95% 1.49-2.73, p < 0.001) and CSM (HR 1.61, CI 95% 1.04-2.49, p < 0.03). CONCLUSIONS: The presence of TT in RCC patients represents a key risk factor for worse perioperative, as well as long-term renal function. Specifically, patients with TT harbor a significant and early estimated glomerular filtration rate (eGFR) decrease. However, despite TT patients show a greater eGFR decline after surgery, they retain acceptable renal function, which remains stable over time.

PDE5is-naïve versus non-naïve patients at first investigation for erectile dysfunction-findings from a long-term, real-life cross-sectional study.

BACKGROUND: Phosphodiesterase 5 inhibitors (PDE5is) represent a first-line pharmacological therapy for erectile dysfunction (ED). Men could obtain PDE5is for recreational purposes without any proper medical prescription. OBJECTIVE: We aimed to analyze clinical characteristics of patients who already used any PDE5i for ED without previous formal medical prescription. MATERIALS AND METHODS: Data from 2012 heterosexual, sexually active men seeking first medical help for ED at our outpatient clinic between 2005 and 2022 were analyzed. All patients were assessed with a comprehensive sexual and medical history and completed the International Index of Erectile Function (IIEF) at baseline. Comorbidities were scored with the Charlson comorbidity index (CCI). Thereof, according to exposure to any PDE5i before their first visit, patients were subdivided into: PDE5i-naïve and non-PDE5i-naïve patients. Descriptive statistics tested the sociodemographic and clinical characteristics of both groups. A logistic regression model predicted the likelihood of being PDE5i-naïve at the baseline. Linear regression analysis (LRA) estimated the likelihood of being PDE5i-naïve versus non-PDE5i-naïve over the analyzed timeframe. Lastly, local polynomial regression models graphically explored the likelihood of being PDE5i-naïve at the first clinical assessment over the analyzed timeframe, and the sensitivity analyses tested the probability of being PDE5i-naïve at baseline. RESULTS: Overall, 1,491 (70.9%) patients were PDE5i-naïve and 611 (29.1%) were non-PDE5i-naïve at the first assessment. PDE5is-naïve patients were younger, with a lower prevalence of CCI ≥ 1 and of normal erectile function (EF) than non-PDE5i-naïve men (all p < 0.05). Multivariable logistic regression found that patients with lower BMI (OR: 0.99), higher IIEF-EF scores (OR: 1.02), lower rates of severe ED (OR: 0.94), and who had been assessed earlier throughout the study timeframe (OR: 1.27) were less likely to be PDE5i-naïve at baseline. Univariate LRA revealed that younger patients (Coeff: -0.02), with lower CCI (Coeff: -0.29) and higher alcohol intake per week (Coeff: 0.52) were more likely to be PDE5i-naïve over the analyzed timeframe. Moreover, for the same IIEF-EF score, patients with higher CCI had lower probability of being PDE5i-naïve. CONCLUSIONS: Self-prescription of PDE5is is an attitude presents in the general population, despite this phenomenon has decreased overtime. Current data outline the importance to keep promoting educational campaigns to promote PDE5is as effective and safe medicinal products, while avoiding their improper use.

Time trends in the use of curative treatment in men 70 years and older with nonmetastatic prostate cancer.

BACKGROUND: Undertreatment of otherwise healthy men in their seventies with prostate cancer has been reported previously. MATERIAL AND METHODS: Using information in a Swedish prostate cancer research database, patterns of management and cancer-specific mortality were compared across age groups in over 70,000 men diagnosed with intermediate- or high-risk nonmetastatic prostate cancer between 2008 and 2020. Crude probabilities of death were estimated non-parametrically. Staging procedures, primary treatment, and cancer death were compared using regression models, adjusting for patient and tumor characteristics. RESULTS: During the study period, the proportion of men treated with curative intent increased in ages 70-74 (intermediate-risk from 45% to 72% and high-risk from 49% to 84%), 75-79 (intermediate-risk from 11% to 52% and high-risk from 12% to 70%), and 80-84 years (intermediate-risk from < 1% to 14% and high-risk from < 1% to 30%). Older age was associated with lower likelihoods of staging investigations and curative treatment, also after adjustment for tumor characteristics and comorbidity. Men treated with curative intent and those initially managed conservatively had lower crude risks of prostate cancer death than men receiving androgen deprivation treatment (ADT). In adjusted analyses, ADT was associated with higher prostate cancer mortality than curative treatment across ages and risk groups. Among men managed conservatively, prostate cancer mortality was higher in ages 70 and above. INTERPRETATION: Use of curative treatment increased substantially in older men with prostate cancer between 2008 and 2020. Our findings suggest reduced age-bias and under-treatment, likely reflecting improved individualized decision-making and adherence to guidelines recommending more active management of older men.

The Role of MUC1 in Renal Cell Carcinoma.

Mucins are a family of high-molecular-weight glycoproteins. MUC1 is widely studied for its role in distinct types of cancers. In many human epithelial malignancies, MUC1 is frequently overexpressed, and its intracellular activities are crucial for cell biology. MUC1 overexpression can enhance cancer cell proliferation by modulating cell metabolism. When epithelial cells lose their tight connections, due to the loss of polarity, the mucins become dispersed on both sides of the epithelial membrane, leading to an abnormal mucin interactome with the membrane. Tumor-related MUC1 exhibits certain features, such as loss of apical localization and aberrant glycosylation that might cause the formation of tumor-related antigen epitopes. Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies and it is the most common kidney cancer. The exact role of MUC1 in this tumor is unknown. Evidence suggests that it may play a role in several oncogenic pathways, including proliferation, metabolic reprogramming, chemoresistance, and angiogenesis. The purpose of this review is to explore the role of MUC1 and the meaning of its overexpression in epithelial tumors and in particular in RCC.

The Importance of Discordant Follicle Stimulating Hormone and Inhibin B Levels in Primary Infertile Men: Findings from a Cross-Sectional Study.

PURPOSE: We aimed to investigate the relationship between follicle stimulating hormone (FSH) and inhibin B (InhB). MATERIALS AND METHODS: Data from 1,230 consecutive men presenting for primary couple's infertility were analyzed. Health-significant comorbidities were scored with Charlson comorbidity index. Quartiles of FSH and InhB were considered to determine threshold values. Descriptive statistics and logistic regression models tested association between FSH and InhB values. RESULTS: Overall, 1,080 (87.8%) men had concordant FSH and InhB values. Conversely, 150 patients (12.2%) had discrepancies in FSH and InhB, with 78 (6.3%) and 72 (5.9%) men reporting both low and high FSH and InhB values, respectively. Infertile men with discordant values were younger (median [interquartile range] 38.0 years [34-41 years] vs. 36.0 years [31-40 years]); had smaller testicular volume (TV) (12 mL [10-15 mL] vs. 15 mL [12-20 mL]); and, had more frequently a sperm DNA fragmentation test >30% (179 [59.1%] vs. 40 [78.4%]) than those with concordant values (all p<0.05). Moreover, a higher frequency of previous cryptorchidism (27.3% vs. 11.9%), lower sperm concentration (3.0 million/mL [0.9-11.0 million/mL] vs. 13.8 million/mL [3.1-36.0 million/mL]), lower progressive sperm motility rates (12.0% [5.0%-25.3%] vs. 20.0% [7.0%-36.0%]), and greater rates of non-obstructive azoospermia (36.4% vs. 23.9%) were found in men with discordant FSH and InhB values (all p≤0.005). At multivariable logistic regression analysis, higher body mass index (odds ratio [OR], 1.08; p=0.001), smaller TV (OR, 0.91; p<0.001), and a history of cryptorchidism (OR, 2.49; p<0.001) were associated with discordant FSH and InhB values. CONCLUSIONS: More than one out of ten infertile men had discordant FSH and InhB values in the real-life setting showing worse clinical profiles than those with concordant levels. Smaller TV and history of cryptorchidism could be used as clinical markers to better tailor the need to test InhB.

Long-term outcomes of penile squamous cell carcinoma in men age ≤50 years old compared with men >50 years old from a single tertiary referral centre: a propensity score matched analysis.

Penile cancer (PeCa) is rare, and the oncological outcomes in younger men are unclear. We aimed to analyse and compare oncological outcomes of men age ≤50 years (y) and >50 years with PeCa. A retrospective analysis of men ≤50 y with penile squamous cell carcinoma managed at a tertiary centre was performed. A propensity score matched cohort of men >50 y was identified for comparison. Matching was according to tumour, nodal stage and the types of primary surgery. Overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS), and metastasis-free survivals (MFS) were estimated using Kaplan-Meier plots and compared using log-rank tests. Between 2005-2020, 100 men ≤50 y (median (IQR) age, 46 y (40-49)) were identified and matched with 100 men >50 y (median (IQR) age, 65 y (59-73)). 10, 24, 32, 34 men age ≤50 y were diagnosed in 2005-2007, 2008-2012, 2013-2016 and 2017-2020 respectively. Median (IQR) follow-up was 53.5 (18-96) months. OS at 2 years: ≤50 y, 86%>50 y, 80.6%; 5 years: ≤50 y, 78.1%, >50 y, 63.1%; 10 years: ≤50 y, 72.3%, >50 y, 45.6% (p = 0.01). DSS at 2 years: ≤50 y, 87.2%>50 y, 87.8%; 5 years: ≤50 y, 80.9%>50 y, 78.2%; 10 years: ≤50 y, 78%, >50 y, 70.9% (p = 0.74). RFS was 93.1% in the ≤50 y group (vs. >50 y, 96.5%) at 2 year, and 90% (vs. >50 y, 88.5%) at 5 years, p = 0.81. Within the ≤50 y group, 2 years and 5 years MFS was 93% (vs. >50 y, 96.5%), and 89.5% (vs. >50 y, 92.7%) respectively, (p = 0.40). There were no statistical significance in DFS, RFS and MFS in men age ≤50 y and >50 y. PeCa in younger patients is fatal, public awareness and patient education are crucial for early detection and management.

Impact of Hydroxyurea to Treat Haematological Disorders on Male Fertility: Two Case Reports and a Systematic Review.

PURPOSE: Hydroxyurea (HU) is a cytoreductive agent used as standard treatment option for sickle cell anaemia/disease (SCD), essential thrombocythemia (ET), and polycythaemia vera (PV). Despite its overall good safety profile, its use also in relatively young patients raises an interest on its potential impact on spermatogenesis. To perform a systematic review of all published articles investigating fertility in male patients affected by SCD, ET, and PV and treated with HU. Two paradigmatic case reports of patients affected by PV and ET, respectively, have been also reported. MATERIALS AND METHODS: PubMed, EMBASE, and Cochrane databases were queried for all the published studies indexed up to November 15th, 2022. A combination of the following keywords was used: "hydroxyurea," "fertility," "male," "sperm," "sickle cell anaemia," "sickle cell disease," "essential thrombocythemia," "polycythaemia vera." RESULTS: Of 48 articles identified, 8 studies, involving 161 patients, were eligible for inclusion. Overall, the number of spermatogonia per round cross section of seminiferous tubule were decreased in patients with SCD compared to healthy males. HU treatment was always associated with a worsening of semen parameters, even up to azoospermia. Notably, treatment discontinuation was associated with an improvement of semen parameters and a trend toward normalization in the case of PV and ET, with a less clear amelioration in men with SCD. In both our patients with either PV or ET, HU discontinuation was associated with a significant improvement of spermatogenesis with successful spontaneous pregnancies. CONCLUSIONS: Published evidence do not consistently report normalization of spermatogenesis after HU discontinuation in SCD cases. Conversely, the literature almost consistently reported an improvement of semen parameters at the discontinuation of HU therapy in PV and ET cases. Our real-life two cases confirmed those findings. The willing of fatherhood and the need for effective fertility treatment warrant further research to improve work-up management in men with hematological disorders.

The Role of 99mTc-Sestamibi Single-photon Emission Computed Tomography/Computed Tomography in the Diagnostic Pathway for Renal Masses: A Systematic Review and Meta-analysis.

CONTEXT: The diagnostic accuracy of current imaging techniques in differentiating benign from malignant neoplasms in the case of indeterminate renal masses is still suboptimal. OBJECTIVE: To evaluate the diagnostic accuracy of 99mTc-sestamibi (SestaMIBI) single-photon emission tomography computed tomography (SPECT)/CT in characterizing indeterminate renal masses by differentiating renal oncocytoma and hybrid oncocytic/chromophobe tumor (HOCT) from (1) all other renal lesions and (2) all malignant renal lesions. Secondary outcomes were: (1) benign versus malignant; (2) renal oncocytoma and HOCT versus clear cell (ccRCC) and papillary (pRCC) renal cell carcinoma; and (3) renal oncocytoma and HOCT versus chromophobe renal cell carcinoma (chRCC). EVIDENCE ACQUISITION: A literature search was conducted up to November 2022 using the PubMed/MEDLINE, Embase, and Web of Science databases. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed to identify eligible studies. Studies included were prospective and retrospective cross-sectional studies in which SestaMIBI SPECT/CT findings were compared to histology after renal mass biopsy or surgery. EVIDENCE SYNTHESIS: Overall, eight studies involving 489 patients with 501 renal masses met our inclusion criteria. The sensitivity and specificity of SestaMIBI SPECT/CT for renal oncocytoma and HOCT versus all other renal lesions were 89% (95% confidence interval [CI] 70-97%) and 89% (95% CI 86-92%), respectively. Notably, for renal oncocytoma and HOCT versus ccRCC and pRCC, SestaMIBI SPECT/CT showed specificity of 98% (95% CI 91-100%) and similar sensitivity. Owing to the relatively high risk of bias and the presence of heterogeneity among the studies included, the level of evidence is still low. CONCLUSIONS: SestaMIBI SPECT/CT has good sensitivity and specificity in differentiating renal oncocytoma and HOCT from all other renal lesions, and in particular from those with more aggressive oncological behavior. Although these results are promising, further studies are needed to support the use of SestaMIBI SPECT/CT outside research trials. PATIENT SUMMARY: A scan method called SestaMIBI SPECT/CT has promise for diagnosing whether kidney tumors are malignant or not. However, it should still be limited to research trials because the level of evidence from our review is low.

The Association Between Insomnia, Insomnia Medications, and Erectile Dysfunction.

BACKGROUND: Sleep quality and duration have been investigated for their association with health. Insomnia affects up to one-third of adults and may impact male erectile function. In addition, medical treatments for insomnia (many of which are sedatives) may also affect erectile quality. OBJECTIVE: To investigate the association of erectile dysfunction (ED) in patients diagnosed with and treated for insomnia. DESIGN, SETTING, AND PARTICIPANTS: We utilized the IBM MarketScan (2007-2016) Commercial and Medicare Supplemental Databases (v 2.0). Age- and enrollment-matched controls were selected among patients without insomnia diagnosis or treatment. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cox proportional hazard models were used to estimate the risk of incident ED (ie, diagnosis alone, or diagnosis and treatment with phosphodiesterase-5 inhibitors [PDE5i], intracavernous injection (ICI)/urethral suppositories, and penile prosthesis) after the diagnosis or treatment of insomnia while adjusting for relevant comorbidities. RESULTS AND LIMITATIONS: In total, 539 109 men with an insomnia diagnosis were identified. Of these men, 356 575 were also medically treated for insomnia. The mean (±standard deviation) follow-up times for patients diagnosed with insomnia and those diagnosed with and treated for insomnia were 2.8 ± 1.6 and 3.1 ± 1.8 yr, respectively. Men with insomnia were more commonly smokers and had a higher number of office visits and comorbidities than controls (p < 0.001). On an adjusted analysis, both untreated and treated insomnia were associated with increased risks of ED diagnosis (hazard ratio or HR [95% confidence interval {CI}]: 1.58 [1.54-1.62] and 1.66 [1.64-1.69], respectively; p < 0.001). Similarly, men with treated insomnia had a higher risk of having ED treated with PDE5i (HR [95% CI]: 1.52 [1.49-1.55]; p < 0.001) and ICI (HR [95% CI]: 1.32 [1.14-1.54]; p < 0.001) when compared with controls. A limitation of this study was that a lack of granularity regarding patient clinical characteristics (eg, severity of disease, laboratory data, etc.) is inherent to insurance claims data. In addition, the follow-up was limited and may affect associations at longer time points. CONCLUSIONS: In the current report, a consistent association between insomnia and ED diagnosis was identified. Men diagnosed with insomnia only were found to have a higher risk of developing ED. Moreover, men with pharmacological insomnia treatments were more often prescribed treatments for ED. Given the prevalence of insomnia, future studies are warranted to delineate the association of insomnia and its treatment with erectile function. PATIENT SUMMARY: Insomnia affects up to one-third of adults and impact male erectile function. Men only diagnosed with insomnia were found to have a higher risk of developing erectile dysfunction (ED). Moreover, men with pharmacological insomnia treatments were more often prescribed treatments for ED.

Atlas of Intracorporeal Orthotopic Neobladder Techniques After Robot-assisted Radical Cystectomy and Systematic Review of Clinical Outcomes.

BACKGROUND: Multiple and heterogeneous techniques have been described for orthotopic neobladder (ONB) reconstruction after robot-assisted radical cystectomy. Nonetheless, a systematic assessment of all the available options is lacking. OBJECTIVE: To provide the first comprehensive step-by-step description of all the available techniques for robotic intracorporeal ONB together with individual intraoperative, perioperative and functional outcomes based on a systematic review of the literature. DESIGN, SETTING, AND PARTICIPANTS: We performed a systematic review of the literature, and MEDLINE/PubMed, Embase, Scopus, and Web of Science databases were searched to identify original articles describing different robotic intracorporeal ONB techniques and reporting intra- and perioperative outcomes. Studies were categorized according to ONB type, providing a synthesis of the current evidence. Video material was provided by experts in the field to illustrate the surgical technique of each intracorporeal ONB. SURGICAL PROCEDURE: Nine different ONB types were identified: Studer, Hautmann, Y shape, U shape, Bordeaux, Pyramid, Shell, Florence Robotic Intracorporeal Neobladder, and Padua Ileal Neobladder. MEASUREMENTS: Continuous and categorical variables are presented as mean ± standard deviation and as frequencies and proportions, respectively. RESULTS AND LIMITATIONS: Of 2587 studies identified, 19 met our inclusion criteria. No cohort studies or randomized control trials comparing different neobladder types are available. Available techniques for intracorporeal robotic ONB reconstruction have similar operative time, estimated blood loss, intraoperative complications, and length of stay. Major variability exists concerning postoperative complications and functional outcomes, likely related to reporting bias. CONCLUSIONS: Several techniques are described for intracorporeal ONB during robot-assisted radical cystectomy with comparable perioperative outcomes. We provide the first step-by-step surgical atlas for robot-assisted ONB reconstruction. Further comparative studies are needed to assess any advantage of one technique over others. PATIENT SUMMARY: Patients elected for radical cystectomy should be aware that multiple techniques for robotic orthotopic neobladder are available, but that current evidence does not favor one type over the others.