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.

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.

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.

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.

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.

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 natural history of Peyronie's disease: an ultrasonography-based study.

OBJECTIVES: To define ultrasonographic patterns reflecting different states of Peyronie's disease (PD) and to use them to evaluate the natural history of the disease. MATERIAL AND METHODS: Diagnosis of PD was based on medical and sexual history, physical examination, intracavernosal injection test, and penile ultrasonography. Patients with penile fracture history were excluded from the study. Three groups were formed according to ultrasonographic patterns: solitary hyperechoic lesion without acoustic shadow (group A), moderately hyperechoic multiple scattered calcified lesions with acoustic shadows (group B), dense calcified hyperechoic plaque with acoustic shadow (group C). All patients entered a watchful waiting protocol for 1 yr followed by a new penile ultrasonography. RESULTS: Ninety-five 95 patients with PD were included in the study (mean age, 57.2+/-9.1 yr; mean duration of disease, 12.9+/-8.9 mo). Risk factors associated with cardiovascular disease were present in 79 of 95 patients (83.16%). Eleven (11.6%), 35 (36.8%), and 49 (51.6%) patients were classified into groups A, B and C, respectively. At the end of the study, in group A, reduction of fibrotic lesions and curvature angle was noticed in 9 of 11 (81.8%) patients, whereas plaque formation was noticed in 2 of 11 (18.2%) patients. In group B, plaque and curvature reduction was noticed in 15 of 35 (42.9%) and 12 of 35 (34.3%) respectively, whereas in the rest a dense calcified plaque was noticed. In group C, no ultrasonographic evidence of improvement was noticed; curvature angle was reduced in 4 of 49 (8.2%), owing to the extension of the plaque circumferentially. Significant hemodynamic changes were noticed at the two time points tested (30.53% diagnosed with vascular disease at baseline vs. 46.32% at the end of the study, p=0.03). CONCLUSIONS: Corporal ultrasonography in patients with PD allows objective evaluation and classification of disease. The density of echogenic areas and presence of acoustic shadows are predictors of disease stability.

Treatment strategy for "non-responders" to tadalafil and vardenafil: a real-life study.

OBJECTIVES: To develop and test step-wise treatment strategy for erectile dysfunction "non-responders" to tadalafil and vardenafil. MATERIAL AND METHODS: Two groups [tadalafil-treated (TG); vardenafil-treated (VG)] of 100 consecutive patients complaining of non-response to treatments were enrolled in three-phase study. Phase 1: inadequate use was identified and patients were rechallenged, after receiving detailed usage information. Phase 2: true non-responders were given new instructions based on drugs' pharmacologic profiles: TGs were dosed at least 2 h before intercourse; VGs were dosed only in fasted state. Remaining non-responders entered phase 3: continuous administration of 20 mg tadalafil every other day, or 20 mg vardenafil every day for 2 weeks. Efficacy was based on positive (yes) response to two questions: "Were your erections rigid, and did they last long enough to have successful intercourse?" and "Do you want to repeat your prescription?" RESULTS: Tadalafil group: Inappropriate use was recognized in 32 patients; 14 (43.75%) responded after adequate instruction. Phase 2: 32 of 86 (37.2%) had intercourse at least 2 h after dose intake. Phase 3: 6 of 86 (11.1%) responded to continuous administration. Overall salvage rate was 52 of 100 (52%). Vardenafil group: Inappropriate use was recognized in 38 patients; 12 (31.58%) responded after adequate instruction. Phase 2, 22 of 88 (25%) responded to dosing in a fasted state. Phase 3: 12 of 66 (18.2%) responded to daily dosing. Overall salvage rate was 46 of 100 (46%). CONCLUSIONS: Following proposed treatment strategy may maximize response rate to phosphodiesterase 5 inhibitors; appropriate usage instructions may play significant role in response rate.

Psychiatric morbidity is frequently undetected in patients with erectile dysfunction.

PURPOSE: We investigated the prevalence of psychiatric morbidity in patients with erectile dysfunction (ED). MATERIALS AND METHODS: Consecutive patients who attended an andrology outpatient clinic complaining of ED were recruited for study purposes. ED severity was evaluated by the International Index of Erectile Function erectile function domain score. The psychiatric diagnosis was established by a semistructured clinical interview as well as by the Mini International Neuropsychiatric Interview 5 Diagnostic and Statistical Manual of Mental Disorders-IV. The Beck Depression Inventory was also incorporated as a complementary tool to assess depressive symptom severity. RESULTS: The study included 103 patients 20 to 76 years old (mean age +/- SD 47.06 +/- 14.78) with ED. Most patients were classified with moderate and severe ED (26.2% and 44.7%, respectively). A detectable psychiatric condition was present in 63.1% of the patients, including depressive disorders in 25.2%, anxiety disorders in 11.7%, depression-anxiety comorbidity in 6.8% and personality disorders in 5.8%. A positive psychiatric anamnesis was identified in 41 cases, while 24 were newly diagnosed. No significant association was found between the duration and severity of ED, and psychiatric morbidity or the severity of depressive symptoms (p > 0.05). A positive association was found between the severity of depressive symptoms and the patient tendency to discuss the problem with their partner (p < 0.01). CONCLUSIONS: Psychiatric morbidity is highly prevalent in patients with ED, potentially affecting treatment outcome. Because lifetime psychological problems were reported by more than half of the patients, a psychosocial history seems mandatory. Partner support appeared to have a significant role in the patient psychological state.

Sildenafil failures may be due to inadequate patient instructions and follow-up: a study on 100 non-responders.

OBJECTIVE: The objective of this study was to identify factors that affect efficacy response rate to sildenafil in the clinical practice. MATERIAL AND METHOD: The study comprised 100 consecutive sildenafil non-responders. Mean patient age was 59+/-14.4 years and mean duration of ED 5.5+/-6.4 years. All patients underwent detailed medical and sexual history and completed the IIEF and a questionnaire regarding the previous use of sildenafil. When inadequate instructions were reported, information on the appropriate use of sildenafil was given and patients were asked to use at least 4 tablets at home. Pharmacologic efficacy was re-evaluated in a scheduled follow-up visit. RESULTS: Mean Erectile Function Domain (ED) of the IIEF score was 14+/-9.9. In 56 patients inappropriate use of sildenafil was recognized; 45 had never used the highest recommended dose (100 mg), 32 had taken the pill with a full stomach right after a meal, 22 had taken the pill just before the initiation of sexual activity and 12 were not aware that sexual stimulation was mandatory to achieve an erection. Furthermore, 8 patients had tried the 100mg dose, despite the presence of factors associated with sildenafil clearance reduction (renal insufficiency, cimetidine treatment). Only 34 patients reported that their physician had scheduled a follow-up visit. Following adequate dose titration and time adjustment, 31 patients responded to sildenafil; 10 patients used the 50 mg dose and 21 the 100 mg. Second and third-line treatment options were offered to the rest of the patients. CONCLUSIONS: ED patients may receive inadequate instructions with their prescriptions. Response rate to sildenafil may be maximized after receiving appropriate dose titration and instructions on administration. ED should be treated in the same way as other chronic conditions; follow-up is necessary to evaluate the appropriate application and pharmacologic efficacy of the proposed treatment.