Risk Factors for Testicular Cancer: Environment, Genes and Infections-Is It All?

The incidence of testicular cancer is steadily increasing over the past several decades in different developed countries. If on one side better diagnosis and treatment have shone a light on this disease, on the other side, differently from other malignant diseases, few risk factors have been identified. The reasons for the increase in testicular cancer are however unknown while risk factors are still poorly understood. Several studies have suggested that exposure to various factors in adolescence as well as in adulthood could be linked to the development of testicular cancer. Nevertheless, the role of environment, infections, and occupational exposure are undoubtedly associated with an increase or a decrease in this risk. The aim of this narrative review is to summarize the most recent evidence regarding the risk factors associated with testicular cancer, starting from the most commonly evaluated (cryptorchidism, family history, infections) to the newer identified and hypothesized risk factors.

The Role of Testosterone in the Elderly: What Do We Know?

Testosterone is the most important hormone in male health. Aging is characterized by testosterone deficiency due to decreasing testosterone levels associated with low testicular production, genetic factors, adiposity, and illness. Low testosterone levels in men are associated with sexual dysfunction (low sexual desire, erectile dysfunction), reduced skeletal muscle mass and strength, decreased bone mineral density, increased cardiovascular risk and alterations of the glycometabolic profile. Testosterone replacement therapy (TRT) shows several therapeutic effects while maintaining a good safety profile in hypogonadal men. TRT restores normal levels of serum testosterone in men, increasing libido and energy level and producing beneficial effects on bone density, strength and muscle as well as yielding cardioprotective effects. Nevertheless, TRT could be contraindicated in men with untreated prostate cancer, although poor findings are reported in the literature. In addition, different potential side effects, such as polycythemia, cardiac events and obstructive sleep apnea, should be monitored. The aim of our review is to provide an updated background regarding the pros and cons of TRT, evaluating its role and its clinical applicability in different domains.

Micro-Ultrasound in the Diagnosis and Staging of Prostate and Bladder Cancer: A Comprehensive Review.

Background and Objectives: Multiparametric magnetic resonance imaging (mpMRI) of the prostate and prostate-specific membrane antigen positron emission tomography (PSMA PET) are some examples of how the advancement of imaging techniques have revolutionized the diagnosis, staging, and consequently management of patients with prostate cancer (PCa). Although with less striking results, novel radiological modalities have also been proposed for bladder cancer (BCa) in recent years. Micro-ultrasound (MUS) is an imaging examination characterized by high real-time spatial resolution, recently introduced in the urological field. This article aimed to describe the current evidence regarding the application of MUS for the diagnosis and staging of PCa and BCa. Materials and Methods: We designed a narrative review. A comprehensive search in the MEDLINE, Scopus, and Cochrane Library databases was performed. Articles in English-language and published until July 2022 were deemed eligible. Retrospective and prospective primary clinical studies, as well as meta-analyses, were included. Results: MUS-guided prostate biopsy showed high sensitivity (0.91, 95% CI, 0.79-0.97) in the diagnosis of clinically significant PCa (csPCa). It was associated with a higher detection rate of csPCa than a systematic biopsy (1.18, 95% CI 0.83-1.68). No significant difference was found between MUS and mpMRI-guided biopsy in the total detection of PCa (p = 0.89) and in the detection of Grade Groups ≥ 2 (p = 0.92). The use of MUS to distinguish between non-muscle-invasive and muscle-invasive BCa was described, highlighting an up-staging with MUS only in a minority of cases (28.6%). Conclusions: Promising findings have emerged regarding the feasibility and accuracy of MUS in the diagnosis and staging of PCa and BCa. However, the available evidence is limited and should be considered preliminary.

Preoperative Fibrinogen-to-Albumin Ratio as Potential Predictor of Bladder Cancer: A Monocentric Retrospective Study.

Background and objective: Fibrinogen and albumin are two proteins widely used, singularly and in combination, in cancer patients as biomarkers of nutritional status, inflammation and disease prognosis. The aim of our study was to investigate the preoperative fibrinogen-to-albumin ratio (FAR) as a preoperative predictor of malignancy as well as advanced grade in patients with bladder cancer. Materials and Methods: A retrospective analysis of patients who underwent TURBT at our institution between 2017 and 2021 was conducted. FAR was obtained from preoperative venous blood samples performed within 30 days from scheduled surgery and was analyzed in relation to histopathological reports, as was the presence of malignancy. Statistical analysis was performed using a Kruskal−Wallis Test, and univariate and multivariate logistic regression analysis, assuming p < 0.05 to be statistically significant. Results: A total of 510 patients were included in the study (81% male, 19% female), with a mean age of 71.66 ± 11.64 years. The mean FAR was significantly higher in patients with low-grade and high-grade bladder cancer, with values of 80.71 ± 23.15 and 84.93 ± 29.96, respectively, compared to patients without cancer (75.50 ± 24.81) (p = 0.006). Univariate regression analysis reported FAR to be irrelevant when considered as a continuous variable (OR = 1.013, 95% CI = 1.004−1.022; p = 0.004), while when considered as a categorical variable, utilizing a cut-off set at 76, OR was 2.062 (95% CI = 1.378−3.084; p < 0.0001). Nevertheless, the data were not confirmed in the multivariate analysis. Conclusions: Elevated preoperative FAR is a potential predictor of malignancy as well as advanced grade in patients with bladder cancer. Further data are required to suggest a promising role of the fibrinogen-to-albumin ratio as a diagnostic biomarker for bladder tumors.

Advances in Urinary Diversion: From Cutaneous Ureterostomy to Orthotopic Neobladder Reconstruction-A Comprehensive Review.

Bladder cancer ranks as the 10th most prevalent cancer globally with an increasing incidence. Radical cystectomy combined with urinary diversion represents the standard treatment for muscle-invasive bladder cancer, offering a range of techniques tailored to patient factors. Overall, urinary diversions are divided into non-continent and continent. Among the first category, cutaneous ureterostomy and ileal conduit represent the most common procedures while in the second category, it could be possible to describe another subclassification which includes ureterosigmoidostomy, continent diversions requiring catheterization and orthotopic voiding pouches and neobladders. In this comprehensive review, urinary diversions are described in their technical aspects, providing a summary of almost all alternatives to urinary diversion post-radical cystectomy.

Reliability of Multiparametric Magnetic Resonance Imaging in Patients with a Previous Negative Biopsy: Comparison with Biopsy-Naïve Patients in the Detection of Clinically Significant Prostate Cancer.

Background: Multiparametric magnetic resonance is an established imaging utilized in the diagnostic pathway of prostate cancer. The aim of this study is to evaluate the accuracy and reliability of multiparametric magnetic resonance imaging (mpMRI) in the detection of clinically significant prostate cancer, defined as Gleason Score ≥ 4 + 3 or a maximum cancer core length 6 mm or longer, in patients with a previous negative biopsy. Methods: The study was conducted as a retrospective observational study at the University of Naples "Federico II", Italy. Overall, 389 patients who underwent systematic and target prostate biopsy between January 2019 and July 2020 were involved and were divided into two groups: Group A, which included biopsy-naïve patients; Group B, which included re-biopsy patients. All mpMRI images were obtained using three Tesla instruments and were interpreted according to PIRADS (Prostate Imaging Reporting and Data System) version 2.0. Results: 327 patients were biopsy-naïve, while 62 belonged to the re-biopsy group. Both groups were comparable in terms of age, total PSA (prostate-specific antigen), and number of cores obtained at the biopsy. 2.2%, 8.8%, 36.1%, and 83.4% of, respectively, PIRADS 2, 3, 4, and 5 biopsy-naïve patients reported a clinically significant prostate cancer compared to 0%, 14.3%, 39%, and 66.6% of re-biopsy patients (p < 0.0001-p = 0.040). No difference was reported in terms of post-biopsy complications. Conclusions: mpMRI confirms its role as a reliable diagnostic tool prior to performing prostate biopsy in patients who underwent a previous negative biopsy, reporting a comparable detection rate of clinically significant prostate cancer.

Sexual dysfunction: Time for a multidisciplinary approach?

Sexual health impairment is one of the most important issues worldwide, with an increasing number of men and women affected. Specifically in male sexual dysfunction (SD), several risk factors were established such as atherosclerosis, hypertension, diabetes mellitus, smoking or obesity. The co-presence of more than one of risk factors identifies a condition, defined as the metabolic syndrome (MetS), related directly to the SD. However, not all the physicians involved in the MetS management routinely discussed the sexual impairment, increasing the bothering feelings of patients. Furthermore, the lack of knowledge, insufficient time, lack of attention, ambiguities about responsibility, insufficient training and experience, shared among physicians, regarding the communication and treatment of sexual dysfunction, are all reported factors involved in under-valuation of SD. The current paper represents a warning to the experts, with the aim of increasing the awareness of SD among clinicians and to promote the education, training and collaboration with sex therapists, through a multidisciplinary team, that can lead to a holistic approach in SD assessment and treatment.

Mobile health applications in kidney stone disease management: A reliable support for patients?

INTRODUCTION: Mobile health applications (MHAs) represent an interesting issue to assist and improve the quality of life of patients affected by Kidney Stone Disease (KSD). Despite this, their scientific quality and adherence to guidelines are not yet addressed. MATERIAL AND METHODS: On 2 November 2022, we conducted an observational cross-sectional descriptive study of all MHAs on KSD. A search in the Apple App Store and Google Play Store was performed. We reviewed all mobile apps from Apple App Store and Google Play Store for KSD and evaluated their usage in screening, prevention, management, and adherence to EAU guidelines. RESULTS: In total 13 MHA were included in the final analysis. All MHAs, 4 (30.8%) from the Apple App Store and 9 (69.2%) from the Google Play Store are geared towards the patient. Engagement ranged from 1.73 to 4.06; Functionality ranged from 3.17 to 4.75; Aesthetics ranged from 1.9 to 4.12; Information ranged from 2.25 to 4.27, and Subjective quality ranged from 1.58 to 3.23. MHAs reported low and medium adherence to EAU guidelines. CONCLUSIONS: MHAs provide a very useful assistance in several medical fields, including KSD. Despite MHAs development is constantly increasing, the scientific validation, content, and quality are not yet solved. Future research is necessary to improve the quality of the apps and promote new user designed, and high-quality apps.

Ejaculation Sparing Thulium Laser Enucleation of the Prostate: An Observational Prospective Study.

Benign prostatic hypertrophy (BPH) is a condition that appears with advancing age and affects 1/3 of men over 50 years, resulting in filling and emptying symptoms. One of the main limitations of endoscopic techniques for BPH is the occurrence of retrograde ejaculation. The purpose of this prospective observational study is to evaluate the efficacy and feasibility of ejaculation-sparing thulium laser enucleation of the prostate (ES-ThuLEP) in the treatment of BPH-related LUTS and the preservation of ejaculation. Sexually active patients with BPH were enrolled and followed up with at 3, 6, and 12 months after surgery. Personal and pharmacological histories were collected, while three standardized questionnaires­the International Index of Erectile Function short form (IIEF-5), the International Consultation on Incontinence Questionnaire for Male Sexual Matters Associated with Lower Urinary Tract Symptoms Module (ICIQ­MLUTSsex), and the International Prostatic Symptom Score (IPSS)­were administered. In addition, all patients underwent uroflowmetry and an assessment of post-void residual volume (PVR). A total of 53 patients were enrolled. A statistically significant improvement in the IPSS score, maximum flow (Qmax), and post-void volume (PVR) at 3 months, 6 months, and 12 months after surgery was found (p < 0.05), while no statistically significant differences were reported between IIEF-5 scores before and after surgery. A total of 48 patients (88.6%) had preserved ejaculation at 3 months, while 92.4% and 94.3% of patients reported preserved ejaculation at 6 and 12 months, respectively. Nevertheless, some degree of hypoposia was referred, at 3, 6, and 12 months, by 43.7%, 30.6%, and 13.2% of patients, respectively. The ES-ThuLEP technique successfully preserved ejaculation in over 90% of patients, representing an ejaculation-sparing alternative in the treatment of BPH.

Oral Preparation of Hyaluronic Acid, Chondroitin Sulfate, Curcumin, and Quercetin (Ialuril® Soft Gels) for the Prevention of LUTS after Intravesical Chemotherapy.

Intravesical chemotherapy may cause chemical cystitis and related lower urinary tract symptoms (LUTS). The aims of this study were to evaluate the efficacy and safety of an oral preparation of hyaluronic acid (HA), chondroitin sulfate (CS), curcumin, and quercetin (Ialuril® Soft Gels) to reduce the severity of LUTS in patients with a history of bladder cancer (BCa) undergoing intravesical chemotherapy. We designed a monocentric, randomized, double-blind, placebo-controlled pilot trial. Patients referred to our institute between November 2016 and March 2018 were enrolled. All subjects had non-muscle-invasive BCa and received intravesical chemotherapy with mitomycin C (MMC). Patients were randomized 1:1 in two groups (intervention vs. control). All subjects underwent oral administration (Ialuril® Soft Gels or placebo) starting one week before the first weekly instillation and ending 30 days after the last one, subsequently starting one week before each monthly instillation and ending 14 days after it. International prostate symptom score (IPSS) and 0-100 visual analogue scale (VAS) were used to assess the efficacy of the treatment. Adverse events were also described. Patients were evaluated at baseline and after 1, 4, 7, and 13 months of intravesical chemotherapy. A total of 34 patients were enrolled. The median IPSS score was significantly lower in the intervention group compared to the control group at 4 (13 vs. 17 points; p = 0.038), 7 (10 vs. 18 points; p < 0.001), and 13 (10 vs. 17 points; p = 0.002) months. The median VAS score was significantly lower in the intervention group compared to the control group at 7 (22 vs. 37 points; p = 0.021) and 13 (20 vs. 35 points; p = 0.024) months. No AE specifically related to supplement or placebo was recorded. Oral formulation of HA, CS, quercetin, and curcumin could be an effective and safe supportive therapy against chemical cystitis in patients receiving intravesical chemotherapy for BCa.

Male Sexual Dysfunction and Infertility in Spinal Cord Injury Patients: State-of-the-Art and Future Perspectives.

Spinal cord injury (SCI) is a relevant medical and social problem. According to the World Health Organization, the commonly estimated worldwide annual incidence of SCI is 40 to 80 cases per million population. After the SCI experience, most men present with sexual dysfunction (erectile dysfunction (ED) and ejaculatory dysfunction), fertility problems (such as impaired spermatogenesis, abnormalities in sperm viability, motility, and morphology), and systemic disorders such as genitourinary infection and endocrine imbalances. The best options available for managing the ejaculatory disorders in patients suffering from SCI are penile vibratory stimulation (PVS) and electroejaculation (EEJ). Furthermore, the treatment of ED in SCI patients consists of medical therapies including phosphodiesterase 5 inhibitors (PDE5i), intracavernosal injections (ICI), vacuum erection devices (VEDs), and surgical as penile prosthesis (PP). This review provides a snapshot of the current evidence for the mechanisms of sexual dysfunction and infertility in SCI patients, discusses the best management strategies for these conditions, and offers our perspective on the direction of future research.

Impact of Sexual Activity on the Risk of Male Genital Tumors: A Systematic Review of the Literature.

Most cancers are related to lifestyle and environmental risk factors, including smoking, alcohol consumption, dietary habits, and environment (occupational exposures). A growing interest in the association between sexual activity (SA) and the development of different types of tumors in both men and women has been recorded in recent years. The aim of the present systematic review is to describe and critically discuss the current evidence regarding the association between SA and male genital cancers (prostatic, penile, and testicular), and to analyze the different theories and biological mechanisms reported in the literature. A comprehensive bibliographic search in the MEDLINE, Scopus, and Web of Science databases was performed in July 2021. Papers in the English language without chronological restrictions were selected. Retrospective and prospective primary clinical studies, in addition to previous systematic reviews and meta-analyses, were included. A total of 19 studies, including 953,704 patients were selected. Case reports, conference abstracts, and editorial comments were excluded. Men with more than 20 sexual partners in their lifetime, and those reporting more than 21 ejaculations per month, reported a decreased risk of overall and less aggressive prostate cancer (PCa). About 40% of penile cancers (PCs) were HPV-associated, with HPV 16 being the dominant genotype. Data regarding the risk of HPV in circumcised patients are conflicting, although circumcision appears to have a protective role against PC. Viral infections and epididymo-orchitis are among the main sex-related risk factors studied for testicular cancer (TC); however, data in the literature are limited. Testicular trauma can allow the identification of pre-existing TC. SA is closely associated with the development of PC through high-risk HPV transmission; in this context, phimosis appears to be a favoring factor. Sexual behaviors appear to play a significant role in PCa pathogenesis, probably through inflammatory mechanisms; however, protective sexual habits have also been described. A direct correlation between SA and TC has not yet been proven, although infections remain the most studied sex-related factor.

Focus on Silodosin: Pros and Cons of Uroselectivity.

Medical management of lower urinary tract symptoms related to benign prostatic obstruction engages healthcare professionals worldwide. Currently, alpha-1 adrenergic antagonists are strongly recommended as first-line therapy for patients with moderate to severe symptoms because of their safety, efficacy and good tolerability. These agents are highly heterogeneous in terms of pharmacological selectivity for the adrenergic receptor subtypes with silodosin being the agent characterized by the highest α1A/α1B affinity ratio. This property has been proposed to confer to silodosin advantages in terms of bladder outlet obstruction improvement and lower incidence of cardiovascular side effects at the cost of a higher incidence of ejaculatory dysfunction. These aspects should be carefully taken in consideration when personalizing medical therapy for lower urinary tract symptoms related to benign prostatic obstruction.