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.
Kidney transplantation offers a longer life expectancy and a better quality of life than dialysis to patients with end-stage kidney disease. Ischemia-reperfusion injury (IRI) is thought to be a ...cornerstone in delayed or reduced graft function and increases the risk of rejection by triggering the immunogenicity of the organ. IRI is an unavoidable event that happens when the blood supply is temporarily reduced and then restored to an organ. IRI is the result of several biological pathways, such as transcriptional reprogramming, apoptosis and necrosis, innate and adaptive immune responses, and endothelial dysfunction. Tubular cells mostly depend on fatty acid (FA) β-oxidation for energy production since more ATP molecules are yielded per substrate molecule than glucose oxidation. Upon ischemia-reperfusion damage, the innate and adaptive immune system activates to achieve tissue clearance and repair. Several cells, cytokines, enzymes, receptors, and ligands are known to take part in these events. The complement cascade might start even before organ procurement in deceased donors. However, additional experimental and clinical data are required to better understand the pathogenic events that take place during this complex process.
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.
•High-grade non-muscle invasive bladder cancer treated with transurethral resection of bladder tumor (TURB) plus bacillus of Calmette-Guerin (BCG).•Up to 40% of patients have recurrence/progression ...within 2 years despite BCG.•Before starting BCG therapy, a re-TURB is performed within 2 to 6 weeks.•Worse prognosis: multifocality, lymphovascular invasion, and high-grade on re-TURB.•BCG unresponsive patients report worse oncological outcomes.
Seventy-five percent of bladder cancers are non-muscle invasive. The treatment strategy includes the transurethral resection of bladder tumor (TURB) followed by intravesical immunotherapy with the bacillus of Calmette-Guerin (BCG) or chemotherapy, depending on the grade of bladder tumor. Despite a proper BCG intravesical instillations schedule, up to 40% of patients present a failure within 2 years. The aim of this retrospective study was to investigate the predictive factors in the response to BCG in patients with a high-grade non-muscle invasive bladder cancer diagnosis.
Patients with non-muscle invasive bladder cancer from 13 hospitals and academic institutions were identified and treated, from January 1, 2002, until December 31, 2012, with TURB and a subsequent re-TURB for restaging before receiving BCG. Follow-up was performed with urine cytology and cystoscopy every 3 months for 1 year and, successively every 6 months. Univariate and multivariate Cox regression models addressed the response to BCG therapy. Kaplan-Meier overall survival (OS) and cancer-specific survival (CSS) estimates were determined for BCG responsive vs. BCG unresponsive patients.
A total of 1,228 patients with non-muscle invasive bladder cancer were enrolled. Of 257 (20.9%) patients were BCG unresponsive. Independent predictive factors for response to BCG were: multifocality (HR: 1.4; 95% CI 1.05–1.86; P = 0.019), lymphovascular invasion (HR: 1.75; 95% CI 1.22–2.49; P = 0.002) and high-grade on re-TURB (HR: 1.39; 95% CI 1.02–1.91; P = 0.037). Overall survival was significantly reduced in BCG-unresponsive patients compared to BCG-responsive patients at 5 years (82.9% vs. 92.4%, P < 0.0001) and at 10 years (44.2% vs. 74.4%, P < 0.0001). Similarly, cancer-specific survival was reduced in BCG-unresponsive patients at 5 years (90.6% vs. 97.3%, P < 0.0001) and at 10 years (72.3% vs. 87.2%, P < 0.0001).
Multifocality, lymphovascular invasion, and high-grade on re-TURB were independent predictors for response to BCG treatment. BCG-unresponsive patients reported worse oncological outcomes.
There is increasing evidence that thyroid hormones (THs) work in an integrative fashion with androgen receptors (ARs) to regulate gonadal differentiation and reproductive function. Studies reveal ...that THs have interactions with the AR promoter region and increase AR expression. THs also have a role in the regulation of enzymes involved in the biosynthesis of androgens, such as 5α-reductase, which is essential in the conversion of testosterone into its active form, 5α-dihydrotestosterone. Additionally, the presence of androgen response elements in the promoter regions of TH-related genes, such as deiodinases and TH receptor isoforms, has been identified in some vertebrates, indicating a mutual interaction between THs and ARs. Since the androgen signaling pathway, mediated by ARs, plays a key role in the formation and progression of prostate cancer (PCa), the existence of crosstalk between THs and ARs supports the epidemiologic and experimental evidence indicating a relationship between the high incidence of PCa and hyperthyroidism. This article aims to review the role of androgen-TH crosstalk in PCa and its implication in clinical management. As life expectancy is growing these days, it can increase the number of patients with PCa and the critical relevance of the disease. In order to gain better knowledge about PCa and to improve clinical management, it is essential to get better insight into the key factors related to the formation and progression of this cancer.
Renal cell carcinoma (RCC) remains a formidable diagnostic challenge, especially in the context of small renal masses. The quest for non-invasive screening tools and biomarkers has steered research ...towards liquid biopsy, focusing on microRNAs (miRNAs), exosomes, and circulating tumor cells (CTCs). MiRNAs, small non-coding RNAs, exhibit notable dysregulation in RCC, offering promising avenues for diagnosis and prognosis. Studies underscore their potential across various biofluids, including plasma, serum, and urine, for RCC detection and subtype characterization. Encouraging miRNA signatures show correlations with overall survival, indicative of their future relevance in RCC management. Exosomes, with their diverse molecular cargo, including miRNAs, emerge as enticing biomarkers, while CTCs, emanating from primary tumors into the bloodstream, provide valuable insights into cancer progression. Despite these advancements, clinical translation necessitates further validation and standardization, encompassing larger-scale studies and robust evidence generation. Currently lacking approved diagnostic assays for renal cancer, the potential future applications of liquid biopsy in follow-up care, treatment selection, and outcome prediction in RCC patients are profound. This review aims to discuss and highlight recent advancements in liquid biopsy for RCC, exploring their strengths and weaknesses in the comprehensive management of this disease.
Trace metals can be divided into two subgroups considering their pathophysiological effects: the first consists of microelements essential for life (arsenic, cobalt, chromium, copper, fluorine, iron, ...iodine, manganese, molybdenum, nickel, selenium, silicon, tin, vanadium and zinc), implicated in important metabolic processes; the second includes toxic microelements, such as cadmium (Cd), mercury (Hg), chromium (Cr), and lead (Pb) for living organisms, even at low concentrations. These metals contribute to serious consequences for human health, including male infertility. Studies performed in several in vitro and in vivo models revealed that environmental exposure to toxic pollutants, as heavy metals, negatively affects human male fertility. Stem cells, due to their ability to self-renew and differentiate in several cell types, have been proposed as a useful tool in assisted reproductive technology, permitting the spermatogenesis recovery in patients with irreversible infertility. Considering the effects of heavy metals on male fertility and, from a demographic point of view, the decreased fertility ratio, further strategies are required to maintain a sustainable turn-over of 2 children for woman. We discuss here the findings on the biological effects of heavy metal pollution in the male fertility and underline the related socioeconomic impact on population demography.
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