Prostate and gut: Any relationship? A narrative review on the available evidence and putative mechanisms.

BACKGROUND: Gut microbiome is a community of microorganisms that lives in the human intestine and exerts various functions on the host, including metabolic, immunoregulatory, and control over cell proliferation. Gut microbiome alterations have been associated with various pathological conditions, such as diabetes mellitus, obesity, and cardiovascular diseases. Gut-prostate axis is explained by the association between gut microbiome quantitative and functional alterations along with increased intestinal epithelial permeability with prostatediseases. However, the pathophysiological mechanisms and clinical importance of this association are not completely clarified yet. METHODS: We conducted a narrative review of the most relevant articles in the Medline (US National Library of Medicine, Bethesda, MD, USA), Scopus (Elsevier, Amsterdam, The Netherlands) and Web of Science Core Collection (Thomson Reuters, Toronto, ON, Canada) databases. No chronological restrictions were applied, and the most related papers published until December 2023 were included. RESULTS: Gut microbiota (GM) and its metabolites are capable of modifying host androgen level, as well as prostate cancer (PCa) therapy response. Moreover, patients with inflammatory bowel disease have higher rates of prostatitis-like symptoms and a potential risk of developing PCa. CONCLUSIONS: There is evidence that interventions on the GM and its metabolites have a high potential to serve as diagnostic and therapeutic tools for prostate diseases, including PCa.

Serum (-2)proPSA/freePSAratio, (-2)proPSA/freePSA density, prostate health index, and prostate health index density as clues to reveal postoperative clinically significant prostate cancer in men with prostate-specific antigen 2-10 ng/mL.

BACKGROUND: There is a strong clinical need to fill the gap of identifying clinically significant prostate cancer (csPCa) in men with prostate-specific antigen (PSA) gray zone values. Promising, but not definitive results have been obtained using PSA derivatives such as prostate health index (PHI) and PHI density (PHID) and the percentage (-2)proPSA/free PSA (%p2PSA/fPSA). Thus, this study aimed to compare the diagnostic value of PHI, PHID, %proPSA/fPSA, and (-2)proPSA/freePSA density (-2pPSA/fPSAD) for csPCa in the patients with PSA within 2-10 ng/mL. METHODS: Serum samples and clinicopathological features were prospectively collected from 142 patients who underwent robot-assisted radical prostatectomy  between September 2021 and December 2023. According to the inclusion criteria, the patients with total PSA  within 2 and 10 ng/mL and negative or suspicious digital rectal examination  were enrolled. We used two different classifications for csPCa: 1) patients with Gleason score (GS) ≥ 7(4 + 3) and 2) patients with GS ≥ 7(3 + 4). The receiver operating characteristic curves and the area under the curve (AUC) values were used to assess the diagnostic performance. RESULTS: Of the 142 men included, 116 (82%) patients were diagnosed with csPCa as GS ≥ 3 + 4 and 107 (75%) defined as csPCa as GS ≥ 7(4 + 3), respectively. We found that p2PSA/fPSA, p2PSA/fPSAD, PHI, and PHID were significantly higher in csPCa classified as GS ≥ 7(3 + 4) as well as GS ≥ 7(4 + 3), with p-values 0.027, 0.054, 0.0016, and 0.0027, respectively. AUCs of the analyzed variables were higher when used to predict csPCa as GS ≥ 6 compared to csPCa as GS ≥7(4 + 3), with an AUC equal, respectively, to 0.679 (95% CI: 0.571-0.786), 0.685 (95% CI: 0.571-0.799), 0.737 (95% CI: 0.639-0.836), and 0.736 (95% CI: 0.630-0.841) in the first subgroup and with an AUC equal, respectively, to 0.653 (95% CI: 0.552-0.754), 0.665 (95% CI: 0.560-0.770), 0.668 (95% CI: 0.568-0.769), and 0.670 (95% CI: 0.567-0.773) in the second, respectively. Both PHID and p2PSA/fPSAD allowed improvement in the diagnostic accuracy with respect to PHI and p2PSA/fPSA ratio, however the differences were not statistically significant (p = 0.409, 0.180 for csPCa as G ≥ Gleason grade (GG) 2 and 0.558 and 0.087 for csPCa as G ≥ GG3, respectively). We found that PHI, PHID, p2PSA/fPSA ratio, and p2PSA/fPSAD showed higher sensitivity, specificity, and positive predictive value when used to predict csPCa as GG ≥ 2, whereas negative predictive value of all four parameters was higher when used to predict GG ≥ 3. CONCLUSIONS: In men with a PSA level between 2 and 10 ng/mL, PHI and PHID, p2PSA/fPSA, and p2PSA/fPSAD showed good diagnostic performance for postoperative csPCa. However, PHID and p2PSA/fPSAD had a small advantage over PHI which needs to be further investigated for the reduction of unnecessary surgical interventions. This finding suggests that it could be a promising biomarker for making the treatment-decision strategy.

The detection rate for prostate cancer in systematic and targeted prostate biopsy in biopsy-naive patients, according to the localization of the lesion at the mpMRI: A single-center retrospective observational study.

OBJECTIVE: Evaluate the detection rates of systematic, targeted and combined cores at biopsy according to tumor positions in biopsy-naïve patients. MATERIAL AND METHODS: A retrospective analysis of a single-center patient cohort (n = 501) that underwent transrectal prostate biopsy between January 2017 and December 2019 was performed. Multi-parametric MRI was executed as a prebiopsy investigation. Biopsy protocol included, for each patient, 12 systematic cores plus 3 to 5 targeted cores per lesion identified at the mpMRI. Pearson and McNemar chi-squared tests were used for statistical analysis to compare tumor location-related detection rates of systematic, targeted and combined (systematic + targeted) cores at biopsy. RESULTS: Median age of patients was 70 years (IQR 62-72), with a median PSA of 8.5 ng/ml (IQR 5.7-15.6). Positive biopsies were obtained in 67.7% of cases. Overall, targeted cores obtained higher detection rates compared to systematic cores (54.3% vs. 43.1%, p < 0.0001). Differences in detection rates were, however, higher for tumors located at the apex (61.1% vs. 26.3%, p < 0.05) and anteriorly (44.4% vs. 19.3%, p < 0.05). Targeted cores similarly obtained higher detection rates in the posterior zone of the prostate gland for clinically significant prostate cancer. A poor agreement was reported between targeted and systematic cores for the apex and anterior zone of the prostate with, respectively κ = 0.028 and κ = -0.018. CONCLUSION: A combined approach of targeted and systematic biopsy delivers the highest detection rate in prostate cancer (PCa). The location of the tumor could however greatly influence overall detection rates, indicating the possibility to omit (as for the base or posterior zone of the gland) or add (as for the apex or anterior zone of the gland) further targeted cores.

Instant messaging in cancer care.

Instant messaging applications, such as WhatsApp® and Telegram®, have transformed global communication, offering unique business models and minimal user expenses. Unlike traditional SMS, these apps facilitate unlimited, multimedia-rich communication globally, driven by widespread smartphone adoption. This shift not only broadens communication horizons but also enhances privacy compared to conventional voice calls. In healthcare, instant messaging, particularly unidirectional communication, proves impactful, evidenced by trials like TEXT ME and Healthy Text. These studies highlight text messages' efficacy in cardiovascular disease prevention and cancer prevention, demonstrating improved patient outcomes and behavioral changes. Bidirectional communication through instant messaging holds promise in cancer care, facilitating patient-doctor interactions, adverse event management, and medication compliance. Studies on pharmacist-run tele-oncology services and WeChat-based doctor-patient communication showcase positive impacts on chemotherapy monitoring, patient adherence, and overall survival rates. Despite these advantages, challenges arise from the use of widely available apps like WhatsApp and WeChat, including a lack of structure, constant message influx, and potential physician burnout. Innovative solutions, exemplified by the Esperto in chat® platform, introduce structured approaches to doctor-patient communication, addressing financial considerations, scheduling, and maintaining work-life balance for healthcare professionals. In conclusion, while instant messaging revolutionizes healthcare communication, challenges necessitate innovative solutions. Striking a balance between accessibility and safeguarding healthcare professionals' well-being is crucial as the digital transformation of healthcare continues.

Impact of the extent of lymph node dissection on survival outcomes in clinically lymph node-positive bladder cancer.

OBJECTIVE: To determine the oncological impact of extended pelvic lymph node dissection (ePLND) vs standard PLND (sPLND) during radical cystectomy (RC) in clinically lymph node-positive (cN+) bladder cancer (BCa). PATIENTS AND METHODS: In this retrospective, multicentre study we included 969 patients who underwent RC with sPLND (internal/external iliac and obturator lymph nodes) or ePLND (sPLND plus common iliac and presacral nodes) with or without platin-based peri-operative chemotherapy for cTany N1-3 M0 BCa between 1991 and 2022. We assessed the impact of ePLND on recurrence-free survival (RFS) and the distribution of recurrences (locoregional and distant recurrences). The secondary endpoint was overall survival (OS). We performed propensity-score matching using covariates associated with the extent of PLND in univariable logistic regression analysis. The association of the extent of PLND with RFS and OS was investigated using Cox regression models. RESULTS: Of 969 cN+ patients, 510 were 1:1 matched on propensity scores. The median (interquartile range [IQR]) time to recurrence was 8 (4-16) months, and median (IQR) follow-up of alive patients was 30 (13-51) months. Disease recurrence was observed in 104 patients in the ePLND and 107 in the sPLND group. Of these, 136 (27%), 47 (9.2%) and 19 patients (3.7%) experienced distant, locoregional, or both distant and locoregional disease recurrence, respectively. When stratified by the extent of PLND, we did not find a difference in recurrence patterns (P > 0.05). ePLND improved neither RFS (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.70-1.19; P = 0.5) nor OS (HR 0.78, 95% CI 0.60-1.01; P = 0.06) compared to sPLND. Stratification by induction chemotherapy did not change outcomes. CONCLUSION: Performing an ePLND at the time of RC in cN+ patients improved neither RFS nor OS compared to sPLND, regardless of induction chemotherapy status. Pretreatment risk stratification is paramount to identify ideal candidates for RC with ePLND as part of a multimodal treatment approach.

The optimal number of induction chemotherapy cycles in clinically lymph node-positive bladder cancer.

OBJECTIVE: To investigate the optimal number of induction chemotherapy cycles needed to achieve a pathological response in patients with clinically lymph node-positive (cN+) bladder cancer (BCa) who received three or four cycles of induction chemotherapy followed by consolidative radical cystectomy (RC) with pelvic lymph node dissection. PATIENTS AND METHODS: We included 388 patients who received three or four cycles of cisplatin/gemcitabine or (dose-dense) methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), followed by consolidative RC for cTanyN1-3M0 BCa. We compared pathological complete (pCR = ypT0N0) and objective response (pOR = yp ≤T1N0) between treatment groups. Predictors of pCR and/or pOR were assessed using uni- and multivariable logistic regression analysis. The secondary endpoints were overall (OS) and cancer-specific survival (CSS). We evaluated the association between the number of induction chemotherapy cycles administered and survival outcomes on multivariable Cox regression. RESULTS: Overall, 101 and 287 patients received three or four cycles of induction chemotherapy, respectively. Of these, 72 (19%) and 128 (33%) achieved pCR and pOR response, respectively. The pCR (20%, 18%) and pOR (40%, 31%) rates did not differ significantly between patients receiving three or four cycles (P > 0.05). The number of cycles was not associated with pCR or pOR on multivariable logistic regression analyses. The 2-year OS estimates were 63% (95% confidence interval [CI] 0.53-0.74) and 63% (95% CI 0.58-0.7) for patients receiving three or four cycles, respectively. Receiving three vs four cycles was not associated with OS and CSS on uni- or multivariable Cox regression analyses. CONCLUSION: Pathological response and survival outcomes did not differ between administering three or four induction chemotherapy cycles in patients with cN+ BCa. A fewer cycles (minimum three) may be oncologically sufficient in patients with cN+ BCa, while decreasing the wait for definitive local therapy in those patients who end up without a response to chemotherapy. This warrants further validation.

Ischemia-Reperfusion Injury in Kidney Transplantation: Mechanisms and Potential Therapeutic Targets.

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) ß-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.

Unlocking Precision Medicine: Liquid Biopsy Advancements in Renal Cancer Detection and Monitoring.

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.

Carbapenem-Resistant Enterobacteriaceae in Urinary Tract Infections: From Biological Insights to Emerging Therapeutic Alternatives.

Urinary tract infections (UTIs) are the second most frequent type of infection observed in clinical practice. Gram-negative Enterobacteriaceae are common pathogens in UTIs. Excessive antibiotic use in humans and animals, poor infection control, and increased global travel have accelerated the spread of multidrug-resistant strains (MDR). Carbapenem antibiotics are commonly considered the last line of defense against MDR Gram-negative bacteria; however, their efficacy is now threatened by the increasing prevalence of carbapenem-resistant Enterobacteriaceae (CRE). This comprehensive review aims to explore the biological mechanisms underlying carbapenem resistance and to present a focus on therapeutic alternatives currently available for complicated UTIs (cUTIs). A comprehensive bibliographic search was conducted on the PubMed/MEDLINE, Scopus, and Web of Science databases in December 2023. The best evidence on the topic was selected, described, and discussed. Analyzed with particular interest were the clinical trials pivotal to the introduction of new pharmacological treatments in the management of complicated cUTIs. Additional suitable articles were collected by manually cross-referencing the bibliography of previously selected papers. This overview provides a current and comprehensive examination of the treatment options available for CRE infections, offering a valuable resource for understanding this constantly evolving public health challenge.

Conservative treatment for high-risk NMIBC failing BCG treatment: who benefits from adding electromotive drug administration (EMDA) of mitomycin C (MMC) to a second BCG induction cycle?

PURPOSE: Radical cystectomy (RC) is the standard treatment for high-risk non muscle-invasive bladder cancer (NMIBC) failing first BCG treatment. A second BCG course is an option for those patients who refuse RC or are not eligible for it, but its success rate is quite low. Aim of the present study was to determine whether the addition of intravesical electromotive drug administration of mytomicin-C (EMDA-MMC) improved the efficacy of second BCG course. METHODS: Patients with high-risk NMIBC having failed first BCG treatment and having refused RC were offered a second BCG induction course either alone (group A) or combined with EMDA-MMC (group B). Recurrence-free survival (RFS), progression-free survival (PFS) and cancer-specific survival (CSS) were tested. RESULTS: Of the 80 evaluable patients, 44 were in group A and 36 in group B; median follow-up was 38 months. RFS was significantly worse in group A whereas there was no difference in PFS and CSS between the two groups. Stratifying by disease stage, Ta patients receiving combined treatment had statistically better RFS and PFS survival than those receiving BCG only; this difference did not apply to T1 patients. Multivariable analysis confirmed that combined treatment was a significant predictor of recurrence and was close to predict progression. No tested variable was predictive of recurrence or progression in T1 tumours. Among those who underwent RC, CSS was 61.5% in those who had progression and 100% in those who remained with NMIBC. CONCLUSION: Combined treatment improved RFS and PFS only in patients with Ta disease.

Radiomics for the identification of extraprostatic extension with prostate MRI: a systematic review and meta-analysis.

OBJECTIVES: Extraprostatic extension (EPE) of prostate cancer (PCa) is predicted using clinical nomograms. Incorporating MRI could represent a leap forward, although poor sensitivity and standardization represent unsolved issues. MRI radiomics has been proposed for EPE prediction. The aim of the study was to systematically review the literature and perform a meta-analysis of MRI-based radiomics approaches for EPE prediction. MATERIALS AND METHODS: Multiple databases were systematically searched for radiomics studies on EPE detection up to June 2022. Methodological quality was appraised according to Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool and radiomics quality score (RQS). The area under the receiver operating characteristic curves (AUC) was pooled to estimate predictive accuracy. A random-effects model estimated overall effect size. Statistical heterogeneity was assessed with I2 value. Publication bias was evaluated with a funnel plot. Subgroup analyses were performed to explore heterogeneity. RESULTS: Thirteen studies were included, showing limitations in study design and methodological quality (median RQS 10/36), with high statistical heterogeneity. Pooled AUC for EPE identification was 0.80. In subgroup analysis, test-set and cross-validation-based studies had pooled AUC of 0.85 and 0.89 respectively. Pooled AUC was 0.72 for deep learning (DL)-based and 0.82 for handcrafted radiomics studies and 0.79 and 0.83 for studies with multiple and single scanner data, respectively. Finally, models with the best predictive performance obtained using radiomics features showed pooled AUC of 0.82, while those including clinical data of 0.76. CONCLUSION: MRI radiomics-powered models to identify EPE in PCa showed a promising predictive performance overall. However, methodologically robust, clinically driven research evaluating their diagnostic and therapeutic impact is still needed. CLINICAL RELEVANCE STATEMENT: Radiomics might improve the management of prostate cancer patients increasing the value of MRI in the assessment of extraprostatic extension. However, it is imperative that forthcoming research prioritizes confirmation studies and a stronger clinical orientation to solidify these advancements. KEY POINTS: • MRI radiomics deserves attention as a tool to overcome the limitations of MRI in prostate cancer local staging. • Pooled AUC was 0.80 for the 13 included studies, with high heterogeneity (84.7%, p < .001), methodological issues, and poor clinical orientation. • Methodologically robust radiomics research needs to focus on increasing MRI sensitivity and bringing added value to clinical nomograms at patient level.

Sexual desire, mood disorders and sleep disturbances in female BMS patients: A controlled study.

BACKGROUND: Burning mouth syndrome is a chronic orofacial pain with intraoral burning and other oral dysaesthetic symptoms that significantly affects the quality of life. The aim of this study is to evaluate the sexual desire in women with BMS and to investigate the possible related factors. METHODS: A case-control study was performed. BMS patients were enrolled according to the International Classification of OroFacial Pain criteria. Demographic variables were collected. We evaluated pain with the Numeric Rating Scale (NRS), Visual Analogue Scale (VAS) and Total Pain Rating Index (T-PRI), anxiety and depression using the Hospital Anxiety and Depression Scale (HADS-A e HADS-D), sleep disturbances with Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS), and sexual desire using Sexual Desire Inventory (SDI). RESULTS: A total of 50 BMS women and 50 healthy controls were enrolled. Compared with the controls, the BMS patients showed higher scores in the NRS (7,81 ± 1,71 vs. 0,14 ± 0.40; p < 0.0001), TPR-I (10,50 ± 4,86 vs. 0,36 ± 1,06; p < 0.0001), HADS-A (11,86 ± 2,85 vs. 3,90 ± 2,81; p < 0.0001), HADS-D (8,04 ± 3,18 vs. 1,42 ± 1,86; p < 0.0001) and PSQI (9,04 ± 2,62 vs. 4,64 ± 3,27; p < 0.0001). The mean SDI in the study group was significantly lower compared to healthy controls (32,36 ± 14,45 vs. 69,70 ± 19,94; p < 0.0001). No correlation was found between SDI and others items explored. CONCLUSION: In line with previous studies, anxiety, depression and sleep disturbances are more common in BMS patients than in healthy population. This pilot study demonstrates for the first time an association between BMS and low sexual desire.

Cancer Stem Cells in Renal Cell Carcinoma: Origins and Biomarkers.

The term "cancer stem cell" (CSC) refers to a cancer cell with the following features: clonogenic ability, the expression of stem cell markers, differentiation into cells of different lineages, growth in nonadhesive spheroids, and the in vivo ability to generate serially transplantable tumors that reflect the heterogeneity of primary cancers (tumorigenicity). According to this model, CSCs may arise from normal stem cells, progenitor cells, and/or differentiated cells because of striking genetic/epigenetic mutations or from the fusion of tissue-specific stem cells with circulating bone marrow stem cells (BMSCs). CSCs use signaling pathways similar to those controlling cell fate during early embryogenesis (Notch, Wnt, Hedgehog, bone morphogenetic proteins (BMPs), fibroblast growth factors, leukemia inhibitory factor, and transforming growth factor-ß). Recent studies identified a subpopulation of CD133+/CD24+ cells from ccRCC specimens that displayed self-renewal ability and clonogenic multipotency. The development of agents targeting CSC signaling-specific pathways and not only surface proteins may ultimately become of utmost importance for patients with RCC.

Complement System and the Kidney: Its Role in Renal Diseases, Kidney Transplantation and Renal Cell Carcinoma.

The crosstalk among the complement system, immune cells, and mediators of inflammation provides an efficient mechanism to protect the organism against infections and support the repair of damaged tissues. Alterations in this complex machinery play a role in the pathogenesis of different diseases. Core complement proteins C3 and C5, their activation fragments, their receptors, and their regulators have been shown to be active intracellularly as the complosome. The kidney is particularly vulnerable to complement-induced damage, and emerging findings have revealed the role of complement system dysregulation in a wide range of kidney disorders, including glomerulopathies and ischemia-reperfusion injury during kidney transplantation. Different studies have shown that activation of the complement system is an important component of tumorigenesis and its elements have been proved to be present in the TME of various human malignancies. The role of the complement system in renal cell carcinoma (RCC) has been recently explored. Clear cell and papillary RCC upregulate most of the complement genes relative to normal kidney tissue. The aim of this narrative review is to provide novel insights into the role of complement in kidney disorders.

Radiogenomics in Renal Cancer Management-Current Evidence and Future Prospects.

Renal cancer management is challenging from diagnosis to treatment and follow-up. In cases of small renal masses and cystic lesions the differential diagnosis of benign or malignant tissues has potential pitfalls when imaging or even renal biopsy is applied. The recent artificial intelligence, imaging techniques, and genomics advancements have the ability to help clinicians set the stratification risk, treatment selection, follow-up strategy, and prognosis of the disease. The combination of radiomics features and genomics data has achieved good results but is currently limited by the retrospective design and the small number of patients included in clinical trials. The road ahead for radiogenomics is open to new, well-designed prospective studies, with large cohorts of patients required to validate previously obtained results and enter clinical practice.

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.

Cytoreductive Nephrectomy and Metastatic Renal Cell Carcinoma: State of the Art and Future Perspectives.

In the past decades, several treatments have been proposed for the management of metastatic renal cell carcinoma (mRCC). Among these, cytoreductive nephrectomy (CN) represents a controversial and open issue in the era of targeted therapy and novel immunotherapy with immune checkpoint inhibitors. Two important studies, CARMENA and SURTIME, analyzed therapy with sunitinib with or without CN, and immediate CN followed by sunitinib versus a deferred CN after three cycles of sunitinib, respectively. CARMENA showed the non-inferiority of sunitinib alone versus sunitinib plus CN, whereas SURTIME showed no difference in progression-free survival (PFS), but a better median OS among patients with deferred CN. Therefore, more prospective clinical trials and appropriate patient identification are necessary to support CN in this new scenario. This review provides a snapshot of the current evidence for CN in mRCC, discusses the management strategies, and offers perspectives on the direction of future research.

The Role of miRNA in Testicular Cancer: Current Insights and Future Perspectives.

Background and Objectives: Despite advancements in the diagnosis and treatment of testicular germ cell tumours (TGTCs), challenges persist in identifying reliable biomarkers for early detection and precise disease management. This narrative review addresses the role of microRNAs (miRNAs) as potential diagnostic tools and therapeutic targets in the treatment of TGCTs. Materials and Methods: Three databases (PubMed®, Web of Science™, and Scopus®) were queried for studies investigating the utility of miRNA as diagnostic tools, assessing their prognostic significance, and evaluating their potential to guide TGCT treatment. Different combinations of the following keywords were used, according to a free-text protocol: "miRNA", "non-coding RNA", "small RNA", "Testicular Cancer", "seminomatous testicular germ cell", "non-seminomatous testicular germ cell". Results: The potential of miRNAs as possible biomarkers for a non-invasive diagnosis of TGCT is appealing. Their integration into the diagnostic pathway for TGCT patients holds the potential to enhance the discriminative power of conventional serum tumour markers (STMs) and could expedite early diagnosis, given that miRNA overexpression was observed in 50% of GCNIS cases. Among miRNAs, miR-371a-3p stands out with the most promising evidence, suggesting its relevance in the primary diagnosis of TGCT, particularly when conventional STMs offer limited value. Indeed, it demonstrated high specificity (90-99%) and sensitivity (84-89%), with good positive predictive value (97.2%) and negative predictive value (82.7%). Furthermore, a direct relationship between miRNA concentration, disease burden, and treatment response exists, regardless of disease stages. The initial evidence of miRNA decrease in response to surgical treatment and systemic chemotherapy has been further supported by more recent results suggesting the potential utility of this tool not only in evaluating treatment response but also in monitoring residual disease and predicting disease relapse. Conclusions: MiRNAs could represent a reliable tool for accurate diagnosis and disease monitoring in the treatment of TGCT, providing more precise tools for early detection and treatment stratification. Nevertheless, well-designed clinical trials and comprehensive long-term data are needed to ensure their translation into effective clinical tools.

New strategy for the identification of prostate cancer: The combination of Proclarix and the prostate health index.

OBJECTIVES: Prostate health index (PHI) and, more recently, Proclarix have been proposed as serum biomarkers for prostate cancer (PCa). In this study, we aimed to evaluate Proclarix and PHI for predicting clinically significant prostate cancer (csPCa). PATIENTS AND METHODS: Proclarix and PHI were measured using samples of 344 men from two different centers. All patients underwent prostate biopsy, and among those, 188 men with PCa on biopsy had an additional radical prostatectomy (RP). All men had a prostate-specific antigen (PSA) between 2 and 10 ng/ml. Evaluation of area under the curve (AUC) and performance at predefined cut-offs of Proclarix and PHI risk scores as well as the linear combination thereof was performed to predict csPCa. PSA density was used as an independent comparator. RESULTS: The cohort median age and PSA were 65 (interquartile range [IQR]: 60-71) and 5.6 (IQR: 4.3-7.2) ng/ml, respectively. CsPCa was diagnosed in 161 (47%) men based on the RP specimen. ROC analysis showed that Proclarix and PHI accurately predicted csPCa with no significant difference (AUC of 0.79 and 0.76, p = 0.378) but significantly better when compared to PSA density (AUC of 0.66, p < 0.001). When using specific cut-offs, Proclarix (cut-off 10) revealed higher specificity and positive predictive value than PHI (cut-off 27) at similar sensitivities. The combination of Proclarix and PHI provided a significant increase in the AUC (p ≤ 0.007) compared to the individual tests alone and the highest clinical benefit was achieved. CONCLUSION: Results of this study show that both Proclarix and PHI accurately detect the presence of csPCa. The model combining Proclarix and PHI revealed the synergistic effect and improved the diagnostic performance of the individual tests.

The relationship between obstructive sleep apnoea and erectile dysfunction: An underdiagnosed link? A prospective cross-sectional study.

This cross-sectional study aimed to investigate the prevalence and clinical characteristics of erectile dysfunction in patients with obstructive sleep apnoea. We enrolled 133 male patients with suspected obstructive sleep apnoea. Ear, nose and throat evaluation, laboratory tests, body mass index, Epworth sleepiness scale, 5-international index of erectile function, overnight ambulatory polygraphy and drug-induced sleep endoscopy patterns were assessed. Eighty patients reported obstructive sleep apnoea. 60% (n = 48) reported erectile dysfunction. Statistically significant correlations were found between 5-International Index of Erectile Function and age, hypertension, diabetes, Epworth sleepiness scale, apnoea-hypopnea index score, O2 saturation-nadir, and oxygen desaturation index. Age, diabetes and O2 saturation-nadir were independent predictors of erectile function. Epworth sleepiness scale, apnoea-hypopnea index score, O2 saturation-nadir, oxygen desaturation index and albumin were higher compared to patients without erectile dysfunction. No statistically significant differences were reported for drug-induced sleep endoscopy patterns and erectile dysfunction. Patients with obstructive sleep apnoea were at significant risk of having erectile dysfunction. Males with obstructive sleep apnoea should be investigated for erectile dysfunction.