Grading Challenges and Prognostic Insights in Chromophobe Renal Cell Carcinoma: A Retrospective Study of 72 Patients.

Chromophobe RCC (ChRCC) carries the best prognosis among all RCC subtypes, yet it lacks a proper grading system. Various systems have been suggested in the past, causing much controversy, and Avulova et al. recently proposed a promising four-tier grading system that takes into consideration tumor necrosis. Dysregulation of the mammalian target of the rapamycin (mTOR) pathway plays a key role in ChRCC pathogenesis, highlighting its molecular complexity. The present retrospective study aimed to evaluate the prognostic factors associated with a more aggressive ChRCC phenotype. Materials and Methods: Seventy-two patients diagnosed with ChRCC between 2004 and 2017 were included in our study. Pathology reports and tissue blocks were reviewed, and immunohistochemistry (IHC) was performed in order to assess the expressions of CYLD (tumor-suppressor gene) and mTOR, among other markers. Univariate analysis was performed, and OS was assessed using the Kaplan-Meier method. Results: In our study, 74% of patients were male, with a mean age of 60 years, and the mean tumor size was 63 mm (±44). The majority (54%) were followed for more than 10 years at intervals ranging between 44 and 222 months. The risk of death was significantly higher for patients that were classified as Grade 4 in the Avulova system (HR: 5.83; 95% CI, 1.37-24.7; p: = 0.017). As far as the IHC is concerned, mTOR expression was associated with an HR of 8.57 (95% CI, 1.91-38.5; p = 0.005), and CYLD expression was associated with an HR of 17.3 (95% CI, 1.57-192; p = 0.02). Conclusions: In our study, the Avulova grading system seems to be positively correlated with OS in patients diagnosed with ChRCC. Furthermore, an elevated mTOR expression also shows a negative correlation with OS, whereas an elevated CYLD expression does not seem to exert a protective role. However, because only a small proportion (4.2%) of our patients died due to ChRCC, despite the long follow-up period, the results must be interpreted with caution. Further research is needed to validate our findings.

Pharmacotherapy for Erectile Dysfunction: Recommendations From the Fourth International Consultation for Sexual Medicine (ICSM 2015).

INTRODUCTION: Treatment of erectile dysfunction is based on pharmacotherapy for most patients. AIM: To review the current data on pharmacotherapy for erectile dysfunction based on efficacy, psychosocial outcomes, and safety outcomes. METHODS: A review of the literature was undertaken by the committee members. All related articles were critically analyzed and discussed. MAIN OUTCOME MEASURES: Levels of evidence (LEs) and grades of recommendations (GRs) are provided based on a thorough analysis of the literature and committee consensus. RESULTS: Ten recommendations are provided. (i) Phosphodiesterase type 5 (PDE5) inhibitors are effective, safe, and well-tolerated therapies for the treatment of men with erectile dysfunction (LE = 1, GR = A). (ii) There are no significant differences in efficacy, safety, and tolerability among PDE5 inhibitors (LE = 1, GR = A). (iii) PDE5 inhibitors are first-line therapy for most men with erectile dysfunction who do not have a specific contraindication to their use (LE = 3, GR = C). (iv) Intracavernosal injection therapy with alprostadil is an effective and well-tolerated treatment for men with erectile dysfunction (LE = 1, GR = A). (v) Intracavernosal injection therapy with alprostadil should be offered to patients as second-line therapy for erectile dysfunction (LE = 3, GR = C). (vi) Intraurethral and topical alprostadil are effective and well-tolerated treatments for men with erectile dysfunction (LE = 1, GR = A). (vii) Intraurethral and topical alprostadil should be considered second-line therapy for erectile dysfunction if available (LE = 3, GR = C). (viii) Dose titration of PDE5 inhibitors to the maximum tolerated dose is strongly recommended because it increases efficacy and satisfaction from treatment (LE = 2, GR = A). (ix) Treatment selection and follow-up should address the psychosocial profile and the needs and expectations of a patient for his sexual life. Shared decision making with the patient (and his partner) is strongly recommended (LE = 2, GR = A). (x) Counterfeit medicines are potentially dangerous. It is strongly recommended that physicians educate their patients to avoid taking any medication from unauthorized sources (LE = 2, GR = A). The first seven recommendations are the same as those from the Third International Consultation for Sexual Medicine and the last three are new recommendations. CONCLUSION: PDE5 inhibitors remain a first-line treatment option because of their excellent efficacy and safety profile. This class of drugs is continually developed with new molecules and new formulations. Intracavernosal injections continue to be an established treatment modality, and intraurethral and topical alprostadil provide an alternative, less invasive treatment option.

Current role of local treatments for erectile dysfunction in the real-life setting.

PURPOSE OF REVIEW: Local treatments for erectile dysfunction include intraurethral alprostadil as well as topical alprostadil cream. They are alternative treatment options to oral or intracavernosal treatments that could overcome unmet needs in patient treatment. RECENT FINDINGS: Intraurethral and topical alprostadil are two local methods of delivering an erectogenic drug to the patient. They have an established efficacy and a safety profile without important systemic adverse events. Efficacy data show that they result in significantly improved erections sufficient for sexual intercourse compared with placebo. Comparative efficacy data to other treatments are very limited. There are no specific contraindications to other drugs. They can be offered to patients who do not tolerate or do not respond to oral treatment. They can be also combined to oral treatment as a salvage therapy before proceeding to intracavernosal injections. The major advantages of them are the patient-friendly modality of delivering and the presence of minor local adverse events that are self-limited and mild in nature. Priapism or prolonged erections are very rare with local treatments. SUMMARY: Local treatments can have an important role as a first-line treatment for erectile dysfunction or in drug combinations mainly because of their excellent safety profile.

How to treat erectile dysfunction in men with diabetes: from pathophysiology to treatment.

Erectile dysfunction (ED) is highly prevalent affecting at least 50 % of men with diabetes mellitus (DM). DM may cause ED through a number of pathophysiological pathways. These include neuropathy, endothelial dysfunction, cavernosal smooth muscle structural/functional changes, and hormonal changes. Lifestyle changes, diabetes control, and treatment of hypogonadism are important as the first step in ED management since there is no curative treatment for ED. Phosphodiesterase type 5 inhibitors (PDE5i) are the first-line treatment option. Intracavernous administration of vasoactive drugs is commonly used as a second-line medical treatment when PDE5i have failed. Alprostadil is the most widely used drug in this second-line setting. The combination of papaverine, phentolamine, and alprostadil represents the most efficacious intracavernous pharmacologic treatment option that may save non-responders to alprostadil. Penile prosthesis implantation can be considered in treatment refractory cases, with excellent functional and safety results in the properly informed patients.

Tadalafil once daily improves ejaculatory function, erectile function, and sexual satisfaction in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia and erectile dysfunction: results from a randomized, placebo- and tamsulosin-controlled, 12-week double-blind study.

INTRODUCTION: Tadalafil, a long-acting phosphodiesterase type 5 inhibitor, is approved for treating signs and symptoms of benign prostatic hyperplasia (BPH) and erectile dysfunction (ED); tamsulosin, an alpha-blocker, is approved for treating signs and symptoms of BPH. AIM: To determine the effects of tadalafil or tamsulosin on sexual function, including ejaculation and orgasm, satisfaction, and erectile function, in sexually active men with ED and lower urinary tract symptoms suggestive of BPH (LUTS/BPH). METHODS: A randomized, double-blind, placebo-controlled study of tadalafil 5 mg once daily for 12 weeks in men with LUTS/BPH; tamsulosin 0.4 mg once daily was an active control. MAIN OUTCOME MEASURES: The International Index of Erectile Function (IIEF) questionnaire was administered at baseline and 4, 8, and 12 weeks. Analysis of orgasm and ejaculation was post hoc based on the IIEF-Orgasmic Function (OF) domain (IIEF-Q9 [ejaculatory frequency] and Q10 [orgasmic frequency]). Other measures included IIEF-Intercourse Satisfaction (IS), Overall Satisfaction (OS), and Erectile Function (EF) domains. Changes from baseline to 12 weeks (or last observation) vs. placebo were analyzed using analysis of covariance. Higher IIEF scores indicate better functioning. RESULTS: Of 511 study participants, 310 (60.7%) had ED and were sexually active. The IIEF-OF increased significantly through 12 weeks with tadalafil vs. placebo (P = 0.048), as did IIEF-Q9 (P = 0.045) but not IIEF-Q10 (P = 0.100). Compared with placebo, IIEF-OF, Q9, and Q10 decreased significantly with tamsulosin (all P < 0.05). The IIEF-IS and OS increased significantly at end point with tadalafil (both P < 0.001); for tamsulosin, change was not significant for IS, while OS decreased significantly (P = 0.009). The IIEF-EF domain increased significantly vs. placebo with tadalafil (P < 0.001) but not tamsulosin (P = 0.699). CONCLUSIONS: Tadalafil 5 mg once daily significantly improved ejaculation and orgasm, intercourse and overall satisfaction, and erectile function. Men receiving tamsulosin 0.4 mg once daily experienced a decrease in both ejaculatory/orgasmic frequency and overall satisfaction vs. placebo, with no significant effect on erectile function.

Adherence to initial PDE-5 inhibitor treatment: randomized open-label study comparing tadalafil once a day, tadalafil on demand, and sildenafil on demand in patients with erectile dysfunction.

INTRODUCTION: Phosphodiesterase type 5 (PDE-5) inhibitor treatment for erectile dysfunction (ED) is frequently discontinued; adherence may vary depending on the initial regimen. AIM: To evaluate the effects of initiating treatment with tadalafil once a day (OaD), tadalafil on demand (pro re nata [PRN]), or sildenafil PRN on treatment adherence. METHODS: In this multicenter, open-label study, men (≥ 18 years) with ED, naïve to PDE-5 inhibitors, were randomized (1:1:1) to tadalafil 5 mg OaD, tadalafil 10 mg PRN, or sildenafil 50 mg PRN. An 8-week randomized treatment (RT) period (dose adjustment possible) was succeeded by 16 weeks of pragmatic treatment (switches between PDE-5 inhibitors allowed). MAIN OUTCOME MEASURES: Treatment adherence was measured as time to discontinuation of RT (any cause), estimated by Kaplan-Meier product-limit method. Treatment-group differences were estimated as hazard ratio (HR; Cox proportional hazards). RESULTS: Seven hundred seventy patients (mean age 53 years) were randomized to tadalafil OaD (N = 257), tadalafil PRN (N = 252), and sildenafil PRN (N = 261). Kaplan-Meier estimates for patients discontinuing RT were 52.2, 42.0, and 66.7%, respectively. Median time to discontinuation of RT was significantly longer for tadalafil OaD and PRN (130 and >168 days) compared with sildenafil (67 days) (HR [97.5% confidence interval]: 0.66 [0.51, 0.85] and 0.49 [0.37, 0.65]; P < 0.001). Reasons for discontinuation with significant differences between groups (P < 0.05) included "lack of efficacy (duration of erection)" (sildenafil 9.2% vs. tadalafil OaD 4.3%, PRN 2.8%), "time constraints due to short window of action" (sildenafil 4.2% vs. tadalafil OaD 0%, PRN 0.4%), and "feel medication controls my sexual life" (sildenafil 2.7% vs. tadalafil OaD 0%). No between-group differences were found in International Index of Erectile Function-Erectile Function domain change from baseline to end of RT (least squares mean: 9.4-10.0, P = 0.359) or discontinuations due to adverse events (1.2-1.6%). The most common adverse event (≥ 4%) was headache. CONCLUSIONS: ED patients assigned to tadalafil OaD or PRN adhered significantly longer to initial treatment than patients assigned to sildenafil PRN. Improvement of erectile function and safety profiles were similar in all three treatment groups.

Testosterone castration levels in patients with prostate cancer: Is there a difference between GnRH agonist and GnRH antagonist? Primary results of an open-label randomized control study.

PURPOSE: To compare testosterone castration levels between patients treated with the gonadotropin-releasing hormone (GnRH) antagonist, degarelix, and GnRH agonist. MATERIALS AND METHODS: Patients with prostate cancer (PCa) of a single outpatient clinic were randomized (2:1) to receive degarelix (group A) or GnRH agonist (group B). The study evaluated testosterone and prostate-specific antigen (PSA) levels, patients' age, Gleason score and the presence of metastases (nodal or bone). Testosterone and PSA levels were measured at 1st, 6th, 12th, and 18th months. Mann-Whitney test and Spearman correlation were used to investigate independent variable while standard multiple regression was performed to explore statistically significant correlations. Kruskal-Wallis test was used to compare testosterone levels at follow-up. RESULTS: The study included 168 patients, 107 in group A and 61 in group B. Testosterone levels at 1st month were significantly lower in patients under GnRH antagonist than those receiving GnRH agonist (group A: 22 ng/dL vs. group B: 29 ng/dL, p=0.011). However, PSA values did not differ significantly between groups (group A: 0.130 ng/mL vs. group B: 0.067 ng/mL, p=0.261). In multivariate analysis, treatment with degarelix was an independent factor of lower testosterone levels at 1st month (p=0.013). Comparison of testosterone levels at 6, 12, and 18 months did not reveal any significant difference within each group. CONCLUSIONS: In patients with PCa who are candidates for androgen deprivation therapy, the administration of GnRH antagonist seems to achieve significantly lower testosterone levels compared to treatment with GnRH agonist at 1st month of treatment.

Development of a new optical device and its feasibility in prostate cancer detection.

AIM: To develop a new optical device (prostate optical device, POD) for assessment of prostate tissue stiffness and evaluate its sensitivity and specificity in prostate cancer detection. PATIENTS AND METHODS: POD was tested in prostate phantoms and in patients with indications for prostate biopsy. Its sensitivity and specificity were compared to digital rectal examination (DRE) and transrectal ultrasonography (TRUS). RESULTS: POD was able to identify stiffness differences on each prostate phantom. 45 patients were included in the study. Sensitivity of TRUS (40%) was significantly lower to POD (85.7%) and DRE (74.3%) (p = 0.000 and p = 0.003, respectively). There was no statistical difference between POD and DRE (p = 0.221). The combination of POD and DRE showed the highest sensitivity (88.6%), positive predictive value (81.6%), and negative predictive value (42.9%) among all diagnostic tests. CONCLUSIONS: POD identified prostatic stiffness differences with the same sensitivity of DRE performed by an experienced urologist providing an objective indication for prostate biopsy and early prostate cancer detection.

Methylation of PCDH17 and NEFH as prognostic biomarker for nonmetastatic RCC: A cohort study.

DNA methylation makes up a main part of the molecular mechanism of cancer evolution and has shown promising results in the prognosis of renal cell cancer (RCC). In this study, we investigated the possible association of promoter methylation of PCDH17, NEFH, RASSF1A, and FHIT, genes with the prognosis of nonmetastatic RCC patients. Cancerous and normal adjacent tissues from surgical specimens of 41 patients with long follow-up were treated for DNA isolation and bisulfite conversion. The gene promoter methylation was determined with quantitative methylation-specific PCR (qMSP). Wilcoxon signed-rank test was used for paired methylation comparisons, while univariate linear regression and Mann-Whitney test were applied for associating methylation status with clinical and disease characteristics. Cox regression proportional hazards models and Kaplan-Meier plots were used for survival analyses in reference to methylation status. Paired comparisons showed tissue-specific hypermethylation for PCDH17 (P < .001), NEFH (P < .001), RASSF1A (P = .032), while a positive association of methylation in normal tissues with age was demonstrated for PCDH17 (P < .001), RASSF1A (P < .001), FHIT (P < .001). PCDH17 was more methylated in cases with clear cell RCC (P = .015) and high-grade tumor (P = .013), while NEFH methylation was higher in locally advanced cases (P = .032). PCDH17 hypermethylation in cancerous and normal tissues was linked to shorter disease-specific survival (DSS, P = .026, P = .004), disease-free survival (DFS, P = .004, P = .019) while NEFH hypermethylation in cancerous tissues was related to shorter DSS (P = .032). Increased methylation difference of NEFH was also associated with shorter DSS (P = .041) and DFS (P = .020), while the corresponding parameter for PCDH17 was associated with poor DFS (P = .014). Kaplan-Meier curves for hypermethylation in cancer tissues demonstrated different clinical courses for PCDH17 (P = .017), NEFH (P = .023) regarding DSS, and PCDH17 (P = .001) regarding DFS. Our study not only highlights the prognostic value of promoter methylation of PCDH17 and NEFH in cancer tissues but also is the first report of the prognostic value of methylation alterations in normal tissues. Our findings are the first report of the prognostic value of methylation alterations in normal tissues, which can contribute to improved assessment of recurrence risk.

Calculating interfractional prostate motion during radiation therapy course using fiducial markers.

PURPOSE: In this study we evaluated the day to day prostate displacement during radiation therapy by using implanted radiopaque fiducials and daily image guided position verification. METHODS: The data of 10 patients that received radiation therapy to the prostate were analyzed. Three fiducial markers were implanted in the prostate before treatment initiation for everyday verification of the target's position. Daily X ray images (kilovolt/KV films) of the pelvis were acquired for verification and were matched with baseline images produced during treatment preparation using bony structures and fiducials as landmarks. We calculated the mean difference between the two methods and the prostate displacement derived from these measurements. RESULTS: A total of 208 KV films were obtained. Our results showed a non-uniform prostate motion, with most of the displacements observed in the caudal direction followed by anterior, posterior, cranial, right and left. The mean target motion in each of the above directions was 3.5 mm, 3.5 mm, 3.3 mm, 3.9 mm, 2 mm and 2.4 mm. Based on the cumulative frequency of the target's displacement, a margin of 8 mm, 7mm, 5 mm, 4 mm, 9 mm and 7 mm in the anterior, posterior, left, right, cranial and caudal direction respectively would account for 95% of prostate's motion, provided that every day KV image guidance is performed. CONCLUSION: A non-isotopic margin of 8 mm, 7mm, 5 mm, 4 mm, 9 mm and 7 mm around the prostate can be considered safe for treatment delivery.

The effect of statins on semen parameters in patients with hypercholesterolemia: A systematic review.

BACKGROUND: Statins constitute the mainstay of treatment in patients with hypercholesterolemia. However, their effect on semen parameters is unknown. OBJECTIVE: This study aimed to systematically review the best available evidence regarding the effect of statins on ejaculate volume and sperm concentration, motility, morphology, or vitality. MATERIALS/METHODS: A comprehensive search was conducted in PubMed, CENTRAL and Scopus databases up to January 10, 2021. Either randomized-controlled trials or prospective cohorts, conducted in males with hypercholesterolemia, were included. RESULTS: Four studies, published between 1992 and 2014, were eligible. The number of participants ranged from 8 to 120 (n = 161). Study duration ranged from 14 to 48 weeks. The type and dose of statin used were pravastatin 20-80 mg/day and simvastatin 20-40 mg/day. With regard to ejaculate volume (n = 3) and sperm concentration (n = 4), no effect was shown with either pravastatin or simvastatin. Regarding sperm motility, either an increase (n = 2; pravastatin, simvastatin), decrease (n = 1; pravastatin), or no effect (n = 1; pravastatin, simvastatin) was found. With respect to sperm morphology, either a decrease (n = 2; pravastatin, simvastatin) or no effect (n = 2; pravastatin, simvastatin) was shown. Concerning sperm vitality, a single study showed a decrease with simvastatin. Because of the high heterogeneity of the populations studied and the limited number of studies, a meta-analysis was not performed. CONCLUSION: This is the first systematic review on the effect of statins on semen parameters. As there is no evidence for such a detrimental effect, no specific approach has to be suggested regarding the preservation of reproductive function in men with hypercholesterolemia.

Pharmacotherapy for erectile dysfunction.

INTRODUCTION: Pharmacotherapy is the usual initial therapy for most men with erectile dysfunction. AIM: To review the current data relating to the efficacy, tolerability and safety of drugs used in the treatment of men with erectile dysfunction. METHODS: A critical review of the literature relating to the use of pharmacotherapeutic agents was undertaken by a committee of eight experts from five countries, building on prior reviews. MAIN OUTCOME MEASURES: Expert opinion and recommendations were based on grading of evidence-based literature, internal committee dialogue, open presentation, and debate. RESULTS: Almost all currently available evidence relates to sildenafil, tadalafil, and vardenafil. Phosphodiesterase type 5 (PDE5) inhibitors are first-line therapy for most men with erectile dysfunction who do not have a specific contraindication to their use. There is no evidence of significant differences in efficacy, safety, and tolerability between the PDE5 inhibitors and apomorphine. Intracavernosal injection therapy with alprostadil should be offered to patients as second line therapy for erectile dysfunction. Intraurethral alprostadil is a less effective treatment than intracavernosal alprostadil for the treatment of men with erectile dysfunction. CONCLUSIONS: PDE5 inhibitors are effective, safe, and well-tolerated therapies for the treatment of men with erectile dysfunction. Apomorphine, intracavernosal injection therapy with alprostadil, and intraurethral alprostadil are all effective and well-tolerated treatments for men with erectile dysfunction. We recommend some standardization of the assessment of psychosocial outcomes within clinical trials in the field of erectile dysfunction.

Urology during a Crisis: A Management Algorithm.

COVID-19 pandemic has affected more than a million people worldwide causing a public health crisis. Under these unique circumstances, urologists continue to provide essential healthcare services and support healthcare systems, by participating in the treatment of COVID-19(+) patients and sparing vital equipment and hospital beds. However, delivering medical care during the pandemic requires strategic planning for all surgical and outpatient activities. Proposed measures include rescheduling elective non-oncological surgeries and using a prioritization protocol for oncological surgeries according to hospital capacity. Following that, outpatient clinics could be partly replaced by telemedicine. Additionally, urologists should be trained in screening and treating patients with COVID-19 during their daily routine.  In order to efficiently provide their services, a management protocol for suspected or known COVID-19 urological patients should be implemented. Furthermore, preventive measures for the nosocomial dispersion of the virus and training on self-protective equipment is mandatory for all physicians. Finally, organizational planning for the best utilization of the staff is of utmost importance. Implementation and adaptation of the protocols according to local requirements and guidelines will ameliorate the quality of services and population's health status. Finally, enhancement of current practices will prepare health systems for future crisis.

The impact of burnout and occupational stress on sexual function in both male and female individuals: a cross-sectional study.

Burnout and occupational stress are common problems in the modern society. The aim of the study was to investigate the association of burnout and occupational stress with sexual dysfunction. The study enrolled 251 residents, 143 males and 108 females. The personal medical history, demographics, and professional data of the participants were recorded. The Copenhagen Burnout Inventory (CBI) and the job stress measure were used for the evaluation of burnout and occupational stress, correspondingly. The International Index of Erectile Function (IIEF) and the Female Sexual Function Index (FSFI) were used for the assessment of sexual function. The majority of the respondents were males (57%), with a mean age of 31 years. From the analysis concerning males, personal burnout, hypertension, and alcohol consumption correlated independently with erectile dysfunction (p = 0.001) and reduced total satisfaction (p < 0.001). With respect to the female participants, the number of children was found to be related to easier arousal (p = 0.009), better lubrication (p = 0.006), and orgasm (p = 0.016). Contrariwise, job stress related negatively with lubrication (p = 0.031) and orgasm (p = 0.012). This is the first study examining the effect of burnout on sexual function. Personal burnout was observed to be associated with sexual dysfunction in men whereas job stress correlated with female sexual problems. Further examination in different occupational groups and a greater number of patients is required.

Systemic therapy for chromophobe renal cell carcinoma: A systematic review.

BACKGROUND: Chromophobe renal cell carcinoma (chRCC) subtype accounts for almost 5% of total RCC cases. It carries the best prognosis among the rest of RCC types. However, patients with metastatic chRCC disease have worse prognosis than patients with advanced clear cell RCC. Furthermore, available data regarding systemic therapy for chRCC patients are scarce and confusing. AIM: The aim of this systematic review is to search for and critically appraise studies that investigate the results of systemic therapies in patients diagnosed with metastatic chRCC disease. METHODS: Search strategy included PUBMED, CENTRAL, clinicaltrials.gov databases, and abstracts of major conferences with a focus on urologic oncology (till March 2019). Studies investigating patients that were treated with systemic therapy for advanced chRCC disease were included. Primary outcomes were progression-free survival and objective response rate. Secondary outcome was overall survival. Screening of available studies was carried out by 2 groups of reviewers, as well as the quality assessment of the included studies. RESULTS: The systematic search yielded 369 studies, of which 15 studies (2 randomized control trials and 13 cohort studies), involving 183 patients, met the eligibility criteria. The 2 randomized control trials that directly compared sunitinib vs. everolimus, suggested an advantage for sunitinib without being statistically significant. Furthermore, sunitinib seems to be superior than sorafenib at least in terms of objective response rate. Regarding mTOR inhibitors, they may have a role in a specific subset of chRCC patients, that needs to be further explored. Finally, as far as immunotherapy is concerned, available data suggest that chRCC seems to be resistant to recent immune check point inhibitors, since just a few tumor responses were observed with the administered immunotherapy regiments. CONCLUSION: The optimum therapy for metastatic chRCC is still missing, as results from ongoing trials are awaited. More studies, of high quality and adequate sample size, that will be based on the specific biology of chRCC, have to be carried out in order to identify the best treatment.

Late results of a randomized trial on the role of mild hypofractionated radiotherapy for the treatment of localized prostate cancer.

Background: Prostate cancer is considered to be highly sensitive to changes in radiation therapy dose per fraction, specifically to hypofractionation. An increase in the fractionation dose could cause a higher increase to the prostate than to the normal tissues leading to better disease control with less toxicity. Here we present the results of a randomized trial comparing mild hypofractionation to conventional fractionation after a median of 3,6 years follow up. Patients and Methods: 139 patients were randomized to receive either hypofractionated radiotherapy with 2,25 Gy/fr to a total of 72 Gy (arm 1) or conventionally fractionated treatment with 2Gy/fr to a total of 74 Gy (arm 2). 72 patients were assigned to arm 1 and 67 to arm 2. Results: After a median follow up of 3,6 years, 23 patients (31,9%) from arm 1 developed grade≥ 2 acute genitourinary toxicity and 21 (31,3%) from arm 2 (p=0,79). The corresponding values from gastrointestinal were 15 (20,8%) and 12 (17,9%) (p=0,6). For late toxicity from GU, 8 patients (11,1%) developed grade≥ 2 symptoms in arm 1 and 7 (10,4%) in arm 2 (p=0,92). late GI toxicity grade≥ 2 was observed in 8 (11,1%) patients in arm 1 and 8 (11,9%) in arm 2 (p=0,88). In multivariate analysis, hormone therapy was significantly associated with late GI events, while acute toxicity from both GU and GI was a prognostic factor of late adverse reaction. Conclusion: No difference in the toxicity profile could be identified between hypofractionation and conventional fractionation. Our schedule of 2,25Gy/fr seems safe and tolerable by the patients with acceptable rates of acute and late toxicity.

Use and abuse of Rigiscan in the diagnosis of erectile dysfunction.

INTRODUCTION: Nocturnal penile tumescence and rigidity (NPTR, or, more simply, NPT) studies, with or without the help of a recording computer (Rigiscan), have been traditionally positioned at the head of several erectile dysfunction (ED) diagnostic flowcharts with the aim to distinguish between psychogenic and organic etiology. Shall we continue to consider these tools as a diagnostic gold standard in ED diagnosis? METHODS: Four scientists with expertise and/or interest in the area of ED pathophysiology and diagnosis were asked to contribute their opinions. MAIN OUTCOME MEASURE: To give to The Journal of Sexual Medicine's reader new stimuli to reexamine a still largely utilized tool utilized in sexual medicine's clinical practice. RESULTS: Of the four experts discussing the topic, the first who is the section editor of the Controversy section, believes that NPT/Rigiscan cannot be considered a useful diagnostic tool for differential diagnosis in ED. He is supported by the physiological considerations of the second expert and by the experimental evidence produced and discussed by the expert number four who questions the accuracy, reliability, and usefulness of these tools to measure a critical aspect of the erection physiology which is the adequate rigidity. In contrast, with several good arguments, the third expert still suggests the use of these tools, perhaps not for every man presenting with ED, but at least for the patient with no neurovascular risk factors who presents with a history suggestive of a psychogenic cause. CONCLUSION: The reader will judge if the expensive, complicated, and time-consuming effort to record nocturnal erectile activity is or is not useful anymore for the patient and for orienting the treatment choices.

Is there a place for conservative treatment in Peyronie's disease?

INTRODUCTION: Peyronie's disease (PD) is a relatively common disorder affecting middle aged men. Conservative nonsurgical treatments include oral, topical, and intra-lesional pharmacotherapies, vacuum stretching, and mechanical traction. METHODS: Four people with expertise and/or interest in the area of PD were asked to contribute their opinions with regard to the safety and efficacy of nonsurgical conservative treatments. MAIN OUTCOME MEASURE: To provide food for thought, discussion, and possible further research in a poorly discussed area of sexual medicine. RESULTS: Of the four experts writing on the topic, one believes a combination of medical therapy and penile traction has positive potential for curvature. Another feels that although medical therapies have potential to alleviate pain, there is little evidence to show that they help with curvature or that penile traction helps. A third expert proposes dividing the disease into phases, where patients in the acute phase may benefit from conservative therapy, whereas patients whose disease is stable require surgical intervention. The last expert agrees that the therapy should depend on the stage of the disease, but believes like the first expert that there is a role for traction therapy for patients with stable disease. CONCLUSION: There is a need for guidelines for nonsurgical therapies for patients with PD, but there is a paucity of evidence as to their efficacy.

A conceptual framework for the evolution of sexual medicine and a model for the development of alternative sexual health services: 10-year experience of the center for sexual and reproductive health.

INTRODUCTION: Sexual health services are limited and inadequate to reduce factors that hinder treatment and adequate care, despite the growing interest for public awareness and prevention strategies. AIM: The aim of this study was to present an integrative conceptual framework, which led to the development of a model of alternative sexual health services and the 10-year experience of the practice of the service. MAIN OUTCOME MEASURES: Multiple-level needs assessments. METHODS: The conceptual framework is composed of four distinct elements: (i) it adopts a social/ecological perspective; (ii) it assumes that results are optimal when multiple interventions are used; (iii) interventions are influenced by behavioral theories; and (iv) sexual health is conceptualized through the biopsychosocial model. Based on this model, a Sexual and Reproductive Health Center was developed, dedicated to research, education, and public awareness. RESULTS: Over 10 years of experience show that the present approach constitutes a process which: (i) facilitates our understanding of the needs at individual, community, and system level; and (ii) increases the individuals', community and systems' capacity to control sexual health. CONCLUSION: Alternative models for sexual and reproductive health services should be encouraged, in order for best practices to be explored and identified. In addition, future research in the effectiveness of such interventions shall be beneficial in order for evidence-based interventions to be designed.

The impact of Diabetes Mellitus on Lower urinary tract symptoms (LUTS) in both male and female patients.

INTRODUCTION: Contemporary studies examine the connection of Diabetes Mellitus (DM) with Lower urinary tract symptoms (LUTS), alone or associated with other factors of the metabolic syndrome. However, little research has occurred concerning patients with diabetes of both genders and sexes without other diseases of the lower urinary tract. The aim of this study is to examine the relationship between DM and LUTS. METHODS: The study enrolled 110 patients with DM and 134 healthy individuals. The IPSS questionnaire was used for the evaluation of symptoms from lower urinary tract. Data was analyzed with univariate and multivariate logistic regression using SPSS v.24. RESULTS: Analysis with moderate/severe LUTS as dependent variable and plausible confounding factors (age group, BMI, hypertension, dyslipidemia, years with DM and reported HbA1c) as covariates revealed that only HbA1c levels correlated independently with the presence of moderate/severe LUTS (p = 0,024, OR:2,729, CI:1,144-6,509) in diabetic women, while there was no statistically significant difference between male groups. HbA1c levels' correlation with IPSS-voiding and IPSS- storage score was not statistically significant. Quality of life is also affected in women with diabetes mellitus (p: 0,02). CONCLUSION: Only an increase in HbA1c was independently connected with a deterioration of LUTS in the female group.