The role of environmental factors in influencing health status is well documented. Heavy metals, polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls, dioxins, pesticides, ultrafine ...particles, produced by human activities put a strain on the body's entire defense system. Therefore, together with public health measures, evidence-based individual resilience measures are necessary to mitigate cancer risk under environmental stress and to prevent reproductive dysfunction and non-communicable diseases; this is especially relevant for workers occupationally exposed to pollutants and/or populations residing in highly polluted areas. The Mediterranean diet is characterized by a high intake of fruits and vegetables rich in flavonoids, that can promote the elimination of pollutants in tissues and fluids and/or mitigate their effects through different mechanisms. In this review, we collected evidence from pre-clinical and clinical studies showing that the impairment of male fertility and gonadal development, as well as cancers of reproductive system, due to the exposure of organic and inorganic pollutants, may be counteracted by flavonoids.
Abstract Context Several preclinical reports, randomized controlled trials, systematic reviews, and posthoc analyses corroborate the role of phosphodiesterase type 5 inhibitors (PDE5-Is) in the ...treatment of men with lower urinary tract symptoms (LUTS) associated with benign prostatic enlargement (BPE). Objective Update of the latest evidence on the mechanisms of action, evaluate the current meta-analyses, and emphasize the results of pooled data analyses of PDE5-Is in LUTS/BPE. Evidence acquisition Literature analysis of basic researches on PDE5-Is, systematic literature search in PubMed and Scopus until May 2015 on reviews of trials on PDE5-Is, and collection of pooled data available on tadalafil 5 mg. Evidence synthesis Latest evidences on the pathophysiology of LUTS/BPE has provided the rationale for use of PDE5-Is: (1) improvement of LUT oxygenation, (2) smooth muscle relaxation, (3) negative regulation of proliferation and transdifferentiation of LUT stroma, (4) reduction of bladder afferent nerve activity, and (5) down-regulation of prostate inflammation are the proven mechanisms of action of PDE5-Is. Data from eight systematic reviews demonstrated that PDE5-Is allow to improve LUTS (International Prostate Symptom Score mean difference vs placebo: 2.35–4.21) and erectile function (International Index of Erectile Function mean difference vs placebo: 2.25–5.66), with negligible change in flow rate (Qmax mean difference vs placebo: 0.01–1.43). Pooled data analyses revealed that tadalafil 5 mg once daily allows the clinically-meaningful improvement of LUTS and nocturnal voiding frequency independent of both erectile dysfunction severity and improvement. Conclusions PDE5-Is are safe and effective in improving both LUTS and erectile function in appropriately selected men with LUTS/BPE. Data on the reduction of disease progression, long-term outcomes, and cost-effectiveness analyses are still lacking. Patient summary We reviewed recent literature on phosphodiesterase type 5 inhibitors in men with lower urinary tract symptoms associated with prostatic enlargement. We found evidence to confirm that phosphodiesterase type 5 inhibitors are a valid treatment option for men affected by bothersome urinary symptoms with or without erectile dysfunction.
Introduction
Immunotherapy is changing the way we think about and treat urothelial carcinoma (UC). The PD-1/PD-L1 pathway inhibition has shown robust efficacy, associated with an acceptable toxicity ...profile, in patients with locally advanced and metastatic unresectable disease, addressing a high decades-old unmet medical need.
Material and methods
Using the Pubmed database, we conducted a literature review for English written published articles up to June 2020. The highest available evidence for the immunotherapy treatment of UC with ICIs were evaluated. The leading phase one, two and three clinical trials were considered for inclusion (n = 12). Patient’s data were extracted from studies depicting the UTUC subpopulation.
Results
Two monoclonal antibodies targeting PD-1 (pembrolizumab and nivolumab) and three to its ligand PD-L1 (atezolizumab, avelumab, and durvalumab) have obtained US FDA and EMA approval for the second-line treatment of platinum-pretreated patients, between 2016 and 2019. Atezolizumab and Pembrolizumab are even currently approved in the first-line setting for cisplatin ineligible patients, with PD-L1- positive tumor. The neoadjuvant scenario in localized high-risk disease is still evolving, with the first data available to date limited to the muscle-invasive bladder carcinoma. The management of patients with upper tract urothelial carcinoma (UTUC: renal pelvis and ureters) is complicated by the lack of specific high-level evidence, due to the rarity of the disease. No published studies addressing immunotherapy in UTUC patients only are available. The largest clinical trials aimed at UC patients, regardless of the upper or lower location of the primary tumor, have enrolled a minority of patients with UTUC, providing the data on which our current knowledge is based. However, targeted scientific efforts are needed to improve our level of care.
Conclusions
This review summarizes the main currently available evidence on the use of the PD-1/PD-L1 pathway inhibition with reference to patients presenting with UTUC.
Abstract Context This review focuses on the relationship among sexual dysfunction (SD), lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH), and related therapies. Objective ...We reviewed the current literature to provide an overview of current data regarding epidemiology and pathophysiology of SD and LUTS. Moreover, we analysed the impact of currently available therapies of LUTS/BPH on both erectile dysfunction (ED) and ejaculatory dysfunction and the effect of phosphodiesterase type 5 inhibitors (PDE5-Is) in patients with ED and LUTS. Evidence acquisition We conducted a Medline search to identify original articles, reviews, editorials, and international scientific congress abstracts by combining the following terms: benign prostatic hyperplasia, lower urinary tract symptoms, sexual dysfunction, erectile dysfunction, and ejaculatory dysfunction. Evidence synthesis We conducted a comprehensive analysis of more relevant general population–based and BPH/LUTS or SD clinic-based trials and evaluated the common pathophysiologic mechanisms related to both conditions. In a further step, the overall impact of current BPH/LUTS therapies on sexual life, including phytotherapies, novel drugs, and surgical procedures, was scrutinized. Finally, the usefulness of PDE5-Is in LUTS/BPH was critically analysed, including preclinical and clinical research data as well as possible mechanisms of action that may contribute to the efficacy of PDE5-Is with LUTS/BPH. Conclusions Community-based and clinical data demonstrate a strong and consistent association between LUTS and ED, suggesting that elderly men with LUTS should be evaluated for SD and vice versa. Pathophysiologic hypotheses regarding common basics of LUTS and SD as discussed in the literature are (1) alteration of the nitric oxide (NO)–cyclic guanosine monophosphate (cGMP) pathway, (2) enhancement of RhoA–Rho-kinase (ROCK) contractile signalling, (3) autonomic adrenergic hyperactivity, and (4) pelvic atherosclerosis. The most important sexual adverse effects of medical therapies are ejaculation disorders after the use of some α-blockers and sexual desire impairment, ED, and ejaculatory disorders after the use of α-reductase inhibitors. Minimally invasive, conventional, and innovative surgical treatments for BPH may induce both retrograde ejaculation and ED. PDE5-Is have demonstrated significant improvements in both LUTS and ED in men with BPH; combination therapy with PDE5-Is and α1-adrenergic blockers seems superior to PDE5-I monotherapy.
PubMed, Scopus, and ISI Web of Knowledge databases were searched to identify studies published up to December 2020 on the involvement of urinary and male genital systems in COVID‐19. Sixteen studies ...involving a total of 575 patients (538 males and 37 females) were included in this systematic review. The COVID‐19 phase was available for 479 patients: 426 in the acute and 53 in the recovery phase. De novo lower urinary tract symptoms (LUTS) were observed in 43 patients and deterioration of pre‐existing LUTS in 7. Bladder hemorrhage was observed in three patients and acute urinary retention in one. Regarding the male genital system, scrotal discomfort was observed in 8 patients, swelling in 14, pain in 16, and erythema in 1; low flow priapism was observed in 2 patients. Ultrasound examination identified acute orchitis in 10 patients, acute epididymitis in 7, and acute epididymo‐orchitis in 16. A case–control study reported that patients with moderate COVID‐19 show a significant reduction in sperm concertation, the total number of sperms per ejaculate, progressive motility, and complete motility. In contrast to what is known from the first studies on the subject, this review also includes subsequent studies that give evidence of the involvement of the lower urinary tract and male genital system in COVID‐19.
Autophagy is a complex process involved in several cell activities, including tissue growth, differentiation, metabolic modulation, and cancer development. In prostate cancer, autophagy has a pivotal ...role in the regulation of apoptosis and disease progression. Several molecular pathways are involved, including PI3K/AKT/mTOR. However, depending on the cellular context, autophagy may play either a detrimental or a protective role in prostate cancer. For this purpose, current evidence has investigated how autophagy interacts within these complex interactions. In this article, we discuss novel findings about autophagic machinery in order to better understand the therapeutic response and the chemotherapy resistance of prostate cancer. Autophagic-modulation drugs have been employed in clinical trials to regulate autophagy, aiming to improve the response to chemotherapy or to anti-cancer treatments. Furthermore, the genetic signature of autophagy has been found to have a potential means to stratify prostate cancer aggressiveness. Unfortunately, stronger evidence is needed to better understand this field, and the application of these findings in clinical practice still remains poorly feasible.
Abstract Background The evolution of resistant pathogens is a worldwide health crisis and adherence to European Association of Urology (EAU) guidelines on antibiotic prophylaxis may be an important ...way to improve antibiotic stewardship and reduce patient harm and costs. Objective To evaluate the prevalence of antibiotic-resistant bacterial strains and health care costs during a period of adherence to EAU guidelines in a tertiary referral urologic institution. Design, setting, and participants A protocol for adherence to EAU guidelines for antibiotic prophylaxis for all urologic procedures was introduced in January 2011. Data for 3529 urologic procedures performed between January 2011 and December 2013 after protocol introduction were compared with data for 2619 procedures performed between January 2008 and December 2010 before protocol implementation. The prevalence of bacterial resistance and health care costs were compared between the two periods. Outcome measurements and statistical analysis The outcome measures were the proportion of resistant uropathogens and costs related to antibiotic consumption and symptomatic postoperative infection. We used χ2 and Fisher's exact tests to test the significance of differences. Results and limitations The proportion of patients with symptomatic postoperative infection did not differ (180/3529 5.1% vs 117/2619 4.5%; p = 0.27). A total of 342 isolates from all patients with symptomatic postoperative infections were analysed. The rate of resistance of Escherichia coli to piperacillin/tazobactam (9.1% vs 5.4%; p = 0.03), gentamicin (18.3% vs 11.2%; p = 0.02), and ciprofloxacin (32.3% vs 19.1%; p = 0.03) decreased significantly after protocol introduction. The defined daily dose (DDD) use of ciprofloxacin fell from 4.2 to 0.2 DDD per 100 patient-days after implementation ( p < 0.001). Antibiotic drug costs (€76 980 vs €36 700) and costs related to postoperative infections (€45 870 vs €29 560) decreased following introduction of the protocol ( p < 0.001). Conclusions Adherence to EAU guidelines on antibiotic prophylaxis reduced antibiotic usage without increasing post-operative infection rate and lowered the prevalence of resistant uropathogens. Patient summary We analysed the impact of adherence to European Association of Urology guidelines on antibiotic prophylaxis for all surgical urologic procedures on the prevalence of infections and resistant bacterial strains and on costs. We found that adherence to the guidelines reduced the rate of bacterial resistance, in particular against piperacillin/tazobactam, gentamicin, and ciprofloxacin, and reduced costs without increasing the risk of postoperative infection after urologic procedures. We recommend adherence to the guidelines as an important part of antibiotic stewardship programmes.
To evaluate the role of prostatic inflammation in the development and progression of benign and malignant prostatic diseases.
Preclinical studies demonstrate that the activation of a chronic ...inflammatory prostatic response plays an important role in the pathogenesis and progression of benign prostatic hyperplasia (BPH) and prostate cancer (PCa). Approximately 40-70% of patients with BPH-related lower urinary tract symptoms harbour chronic inflammation at pathologic evaluation. These individuals should be considered at increased risk of symptom progression and acute urinary retention. Although currently available drugs approved for the treatment of BPH do not have an anti-inflammatory activity, the development of novel molecules that target the inflammatory pathway represents a promising area in the pharmacological treatment of BPH. Preclinical evidences support a potential role of chronic prostatic inflammation in the malignant transformation of prostatic cells. However, clinical investigations on the association between prostatic inflammation and the risk of PCa report conflicting results.
Men with BPH-related lower urinary tract symptoms and chronic prostatic inflammation should be considered at increased risk of symptom progression and acute urinary retention during follow-up. Although preclinical studies provide a biological rationale for the relationship between inflammation and the risk of PCa, clinical investigations report conflicting results and the direct relationship between inflammation and malignant transformation in the human prostate is still debated.
Prader-Willi syndrome (PWS) is a multisystemic complex genetic disorder related to the lack of a functional paternal copy of chromosome 15q11-q13. Several clinical manifestations are reported, such ...as short stature, cognitive and behavioral disability, temperature instability, hypotonia, hypersomnia, hyperphagia, and multiple endocrine abnormalities, including growth hormone deficiency and hypogonadism. The hypogonadism in PWS is due to central and peripheral mechanisms involving the hypothalamus-pituitary-gonadal axis. The early diagnosis and management of hypogonadism in PWS are both important for physicians in order to reach a better quality of life for these patients. The aim of this study is to summarize and investigate causes and possible therapies for hypogonadism in PWS. Additional studies are further needed to clarify the role of different genes related to hypogonadism and to establish a common and evidence-based therapy.
Over the last decade, several nephrometry scores (NSs) have been introduced with the aim of facilitating preoperative decision making, planning, and counseling in the field of nephron-sparing ...surgery. However, their predictive role remains controversial.
To describe currently available nephrometry scores and to determine their predictive role for different outcomes by performing a systematic review and meta-analysis of the literature.
PubMed, Embase®, and Web of Science were screened to identify eligible studies. Identification and selection of the reports were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). A pooled analysis of NS predictive role of intraoperative, postoperative, oncological, and functional outcomes was performed. Odds ratio was considered the effect size. All the analyses were performed using Stata 15.0, and statistical significance was set at p≤ 0.05.
Overall, 51 studies meeting our inclusion criteria were identified and considered for the analysis. Except for one prospective randomized trial, all the studies were retrospective. All the studies were found to be of intermediate quality, except for one of high quality. Most studies assessed the predictive role of the Radius-Exophytic/Endophytic-Nearness-Anterior/Posterior-Location (RENAL) and Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) scores, mostly regarding complications after nephron-sparing surgery. RENAL was an independent predictor of an on-clamp procedure (p< 0.001). Mayo Adhesive Probability score was related to adhesive perinephric fat (p= 0.005). Continuous and high-complexity RENAL scores were predictors of warm ischemia time (WIT; p= 0.006 and p< 0.001, respectively). Continuous (p< 0.001) and high-complexity (p< 0.001) PADUA scores were related to WIT. Continuous and high-complexity RENAL scores were predictors of overall complications (p= 0.002 and p< 0.001, respectively). PADUA score was related to complications both as continuous (p< 0.001) and as a categorical value (p< 0.002). The RENAL scores R=3 (p= 0.008), E=2 (p= 0.039), and hilar location (p= 0.006) were predictors of histological malignancy. Continuous and categorical RENAL scores were independent predictors of an estimated glomerular filtration rate (eGFR) increase (p= 0.006 and p< 0.001, respectively). The Diameter-Axial-Polar score (p= 0.018) and Peritumoral Artery Scoring System (PASS; p= 0.02) were also independent predictors.
The literature regarding nephrometry scoring systems is sparse, and mostly focused on RENAL and PADUA, which are easy to calculate and have a good correlation with most outcomes. Renal Pelvic Score is the best predictor of pelvicalyceal entry/repair and urine leak, whereas Surgical Approach Renal Ranking and PASS strongly predict surgical approach and renal function variation, respectively. Other nephrometry scores based on mathematical models are limited by their complexity, and they lack evidence supporting their predictive value.
We reviewed the medical literature regarding the use and value of so-called “nephrometry scores,” which are scoring systems based on radiological imaging and made to grade the complexity of a renal tumor. We analyzed whether these scoring systems can predict some of the outcomes of patients undergoing surgical removal of renal tumors.
The literature on nephrometry scoring systems is sparse, and it is mostly focused on the Radius-Exophytic/Endophytic-Nearness-Anterior/Posterior-Location (RENAL) and Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) scores. The results of this study can aid in further research effort in this field and foster the development of better predictive tools
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