Refining surgical strategies in ThuLEP for BPH: a propensity score matched comparison of En-bloc, three lobes, and two lobes techniques.

PURPOSE: This study compares the peri-operative and functional outcomes of three distinct surgical techniques in Thulium Laser Enucleation of the Prostate (ThuLEP) for benign prostatic hyperplasia (BPH). The main aim is to assess whether the En-bloc, Three-lobe, and Two-lobe techniques have differential effects on surgical efficacy and patient outcomes. METHODS: A retrospective analysis was conducted on patients undergoing ThuLEP for BPH between January 2019 and January 2024 at two tertiary centers. Propensity score matching was utilized to balance baseline characteristics among patients undergoing the different techniques. Surgical parameters, including operative time, enucleation time, morcellation time, energy consumption, and postoperative outcomes, were compared among the groups. RESULTS: Following propensity score matching, 213 patients were included in the analysis. Intraoperative analysis revealed significantly shorter enucleation, laser enucleation, morcellation and operative times and total energy delivered in the En-bloc and Two-lobe groups compared to the Three-lobe group. No significant differences were observed among the groups in terms of intraoperative and postoperative complications. There were no significant differences in functional outcomes at the 3-month follow-up among the groups. CONCLUSION: The findings of this study suggest that while the En-bloc and Two-lobe techniques may offer efficiency benefits and could be considered safe alternatives in ThuLEP procedures, the reduction in laser enucleation time and energy delivered did not necessarily translate into improvements in post operative storage symptoms or other functional outcomes for the patients. Surgeon preference and proficiency may play a crucial role in selecting the most suitable technique for individual patients. Future research should focus on larger-scale prospective studies to further validate these findings and explore potential factors influencing surgical outcomes.

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.

Testicular Cancer Treatments and Sexuality: A Narrative Review.

The incidence of testicular cancer (TC) has been rapidly increasing over the past years. Diagnosis and early treatment have shown good oncological control, guaranteeing the patient different treatment approaches according to histology and tumor stage. Currently, physicians usually prioritize oncological outcomes over sexual outcomes and quality of life, considering as a first aim the overall survival of the patients; however, differently from other neoplasms, quality of life is still strongly affected among TC patients, and sexual outcomes are frequently compromised after each TC treatment. Several studies have suggested that each treatment approach may be associated with sexual dysfunctions, including erectile dysfunction, ejaculatory disorders, fertility issues, and hormonal changes. Since testicular cancer patients are more frequently young men, the subject of this work is substantial and should be analyzed in detail to help specialists in the management of this disease. The aim of the current narrative review is to generally describe every treatment for TC, including surgery, chemotherapy, radiotherapy, and retroperitoneal lymph node dissection, and to establish which sexual dysfunction may be specifically associated with each therapy.

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.

Gender-specific counselling of patients with upper tract urothelial carcinoma and Lynch syndrome.

PURPOSE: Lynch syndrome (LS) is an autosomal dominant genetic syndrome resulting in a wide spectrum of malignancies caused by germline mutations in mismatch repair genes (MMR). Gene mutations have different effects and penetrance between the two genders. The aim of this review is to offer a gender-specific evidence-based clinical guide on diagnosis, screening, surveillance, and counselling of UTUC patients with LS. METHODS: Using MEDLINE, a non-systematic review was performed including articles between 2004 and 2022. English language original articles, reviews, and editorials were selected based on their clinical relevance. RESULTS: Upper tract urothelial carcinoma (UTUC) is the third most common malignancy in Lynch syndrome. Up to 21% of new UTUC cases may have unrecognized LS as the underlying cause. LS-UTUC does not have a clear gender prevalence, even if it seems to slightly prefer the male gender. The MSH6 variant is significantly associated with female gender (p < 0.001) and with gynecological malignancies. Female MSH2 and MLH1 carriers have higher rates for endometrial and ovarian cancer with respect to the general population, while male MSH2 and MLH1 carriers have, respectively, higher rate of prostate cancer and upper GI tract, or biliary or pancreatic cancers. Conflicting evidence remains on the association of testicular cancer with LS. CONCLUSION: LS is a polyhedric disease, having a great impact on patients and their families that requires a multidisciplinary approach. UTUC patients should be systematically screened for LS, and urologists have to be aware that the same MMR mutation may lead to different malignancies according to the patient's gender.

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.

Urinary MicroRNAs as Biomarkers of Urological Cancers: A Systematic Review.

MicroRNAs (miRNAs) are emerging as biomarkers for the detection and prognosis of cancers due to their inherent stability and resilience. To summarize the evidence regarding the role of urinary miRNAs (umiRNAs) in the detection, prognosis, and therapy of genitourinary cancers, we performed a systematic review of the most important scientific databases using the following keywords: (urinary miRNA) AND (prostate cancer); (urinary miRNA) AND (bladder cancer); (urinary miRNA) AND (renal cancer); (urinary miRNA) AND (testicular cancer); (urinary miRNA) AND (urothelial cancer). Of all, 1364 articles were screened. Only original studies in the English language on human specimens were considered for inclusion in our systematic review. Thus, a convenient sample of 60 original articles was identified. UmiRNAs are up- or downregulated in prostate cancer and may serve as potential non-invasive molecular biomarkers. Several umiRNAs have been identified as diagnostic biomarkers of urothelial carcinoma and bladder cancer (BC), allowing us to discriminate malignant from nonmalignant forms of hematuria. UmiRNAs could serve as therapeutic targets or recurrence markers of non-muscle-invasive BC and could predict the aggressivity and prognosis of muscle-invasive BC. In renal cell carcinoma, miRNAs have been identified as predictors of tumor detection, aggressiveness, and progression to metastasis. UmiRNAs could play an important role in the diagnosis, prognosis, and therapy of urological cancers.

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.

Is Systemic Immune-Inflammation Index a Real Non-Invasive Biomarker to Predict Oncological Outcomes in Patients Eligible for Radical Cystectomy?

Background and Objectives: To assess the potential prognostic role of the systemic immune-inflammation index (SII) in predicting oncological outcomes in a cohort of patients treated with radical cystectomy (RC). Materials and Methods: From 2016 to 2022, a retrospective monocentric study enrolled 193 patients who were divided into two groups based on their SII levels using the optimal cutoff determined by the Youden index. The SII was obtained from a preoperative blood test approximately one month before RC. Univariable and multivariable logistic regression analyses were conducted to investigate the capacity of SII to predict lymph node invasion (N), advanced pT stage (pT3/pT4), and locally advanced condition at the time of RC. Multivariable Cox regression models adjusted for preoperative and postoperative features were used to analyze the prognostic effect of SII on recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Results: The optimal cutoff value of the SII was 640.27. An elevated SII was seen in 113 (58.5%) patients. Using the multivariable preoperative logistic regression models, an elevated SII was correlated with nodal invasion (N; p = 0.03), advanced pT stage (p = 0.04), and locally advanced disease (p = 0.005), with enhancement of AUCs for predicting locally advanced disease (p = 0.04). In multivariable Cox regression models that considered preoperative clinicopathologic factors, an elevated SII was linked to poorer RFS (p = 0.005) and OS (p = 0.01). Moreover, on multivariable Cox regression postoperative models, a high SII was linked to RFS (p = 0.004) and to OS (p = 0.01). Conclusions: In this monocentric retrospective study, higher preoperative SII values predicted worse oncological outcomes in patients with bladder cancer (BCa) who underwent RC.

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.

Metabolomic Approaches for Detection and Identification of Biomarkers and Altered Pathways in Bladder Cancer.

Metabolomic analysis has proven to be a useful tool in biomarker discovery and the molecular classification of cancers. In order to find new biomarkers, and to better understand its pathological behavior, bladder cancer also has been studied using a metabolomics approach. In this article, we review the literature on metabolomic studies of bladder cancer, focusing on the different available samples (urine, blood, tissue samples) used to perform the studies and their relative findings. Moreover, the multi-omic approach in bladder cancer research has found novel insights into its metabolic behavior, providing excellent start-points for new diagnostic and therapeutic strategies. Metabolomics data analysis can lead to the discovery of a "signature pathway" associated with the progression of bladder cancer; this aspect could be potentially valuable in predictions of clinical outcomes and the introduction of new treatments. However, further studies are needed to give stronger evidence and to make these tools feasible for use in clinical practice.

Novel Insights into Autophagy and Prostate Cancer: A Comprehensive Review.

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.

Renal Cell Carcinoma as a Metabolic Disease: An Update on Main Pathways, Potential Biomarkers, and Therapeutic Targets.

Clear cell renal cell carcinoma (ccRCC) is the most frequent histological kidney cancer subtype. Over the last decade, significant progress has been made in identifying the genetic and metabolic alterations driving ccRCC development. In particular, an integrated approach using transcriptomics, metabolomics, and lipidomics has led to a better understanding of ccRCC as a metabolic disease. The metabolic profiling of this cancer could help define and predict its behavior in terms of aggressiveness, prognosis, and therapeutic responsiveness, and would be an innovative strategy for choosing the optimal therapy for a specific patient. This review article describes the current state-of-the-art in research on ccRCC metabolic pathways and potential therapeutic applications. In addition, the clinical implication of pharmacometabolomic intervention is analyzed, which represents a new field for novel stage-related and patient-tailored strategies according to the specific susceptibility to new classes of drugs.

The Role of Testosterone in the Elderly: What Do We Know?

Testosterone is the most important hormone in male health. Aging is characterized by testosterone deficiency due to decreasing testosterone levels associated with low testicular production, genetic factors, adiposity, and illness. Low testosterone levels in men are associated with sexual dysfunction (low sexual desire, erectile dysfunction), reduced skeletal muscle mass and strength, decreased bone mineral density, increased cardiovascular risk and alterations of the glycometabolic profile. Testosterone replacement therapy (TRT) shows several therapeutic effects while maintaining a good safety profile in hypogonadal men. TRT restores normal levels of serum testosterone in men, increasing libido and energy level and producing beneficial effects on bone density, strength and muscle as well as yielding cardioprotective effects. Nevertheless, TRT could be contraindicated in men with untreated prostate cancer, although poor findings are reported in the literature. In addition, different potential side effects, such as polycythemia, cardiac events and obstructive sleep apnea, should be monitored. The aim of our review is to provide an updated background regarding the pros and cons of TRT, evaluating its role and its clinical applicability in different domains.

Micro-Ultrasound in the Diagnosis and Staging of Prostate and Bladder Cancer: A Comprehensive Review.

Background and Objectives: Multiparametric magnetic resonance imaging (mpMRI) of the prostate and prostate-specific membrane antigen positron emission tomography (PSMA PET) are some examples of how the advancement of imaging techniques have revolutionized the diagnosis, staging, and consequently management of patients with prostate cancer (PCa). Although with less striking results, novel radiological modalities have also been proposed for bladder cancer (BCa) in recent years. Micro-ultrasound (MUS) is an imaging examination characterized by high real-time spatial resolution, recently introduced in the urological field. This article aimed to describe the current evidence regarding the application of MUS for the diagnosis and staging of PCa and BCa. Materials and Methods: We designed a narrative review. A comprehensive search in the MEDLINE, Scopus, and Cochrane Library databases was performed. Articles in English-language and published until July 2022 were deemed eligible. Retrospective and prospective primary clinical studies, as well as meta-analyses, were included. Results: MUS-guided prostate biopsy showed high sensitivity (0.91, 95% CI, 0.79-0.97) in the diagnosis of clinically significant PCa (csPCa). It was associated with a higher detection rate of csPCa than a systematic biopsy (1.18, 95% CI 0.83-1.68). No significant difference was found between MUS and mpMRI-guided biopsy in the total detection of PCa (p = 0.89) and in the detection of Grade Groups ≥ 2 (p = 0.92). The use of MUS to distinguish between non-muscle-invasive and muscle-invasive BCa was described, highlighting an up-staging with MUS only in a minority of cases (28.6%). Conclusions: Promising findings have emerged regarding the feasibility and accuracy of MUS in the diagnosis and staging of PCa and BCa. However, the available evidence is limited and should be considered preliminary.

Poikilothermic Animals as a Previously Unrecognized Source of Fecal Indicator Bacteria in a Backwater Ecosystem of a Large River.

Quantitative information regarding the presence of Escherichia coli, intestinal enterococci, and Clostridium perfringens in poikilotherms is notably scarce. Therefore, this study was designed to allow a systematic comparison of the occurrence of these standard fecal indicator bacteria (SFIB) in the excreta of wild homeothermic (ruminants, boars, carnivores, and birds) and poikilothermic (earthworms, gastropods, frogs, and fish) animals inhabiting an alluvial backwater area in eastern Austria. With the exception of earthworms, the average concentrations of E. coli and enterococci in the excreta of poikilotherms were equal to or only slightly lower than those observed in homeothermic excreta and were 1 to 4 orders of magnitude higher than the levels observed in the ambient soils and sediments. Enterococci reached extraordinarily high concentrations in gastropods. Additional estimates of the daily excreted SFIB (E. coli and enterococcus) loads (DESL) further supported the importance of poikilotherms as potential pollution sources. The newly established DESL metric also allowed comparison to the standing stock of SFIB in the sediment and soil of the investigated area. In agreement with its biological characteristics, the highest concentrations of C. perfringens were observed in carnivores. In conclusion, the long-standing hypothesis that only humans and homeothermic animals are primary sources of SFIB is challenged by the results of this study. It may be necessary to extend the fecal indicator concept by additionally considering poikilotherms as potential important primary habitats of SFIB. Further studies in other geographical areas are needed to evaluate the general significance of our results. We hypothesize that the importance of poikilotherms as sources of SFIB is strongly correlated with the ambient temperature and would therefore be of increased significance in subtropical and tropical habitats and water resources.IMPORTANCE The current fecal indicator concept is based on the assumption that the standard fecal indicator bacteria (SFIB) Escherichia coli, intestinal enterococci, and Clostridium perfringens multiply significantly only in the guts of humans and other homeothermic animals and can therefore indicate fecal pollution and the potential presence of pathogens from those groups. The findings of the present study showed that SFIB can also occur in high concentrations in poikilothermic animals (i.e., animals with body temperatures that vary with the ambient environmental temperature, such as fish, frogs, and snails) in an alluvial backwater area in a temperate region, indicating that a reconsideration of this long-standing indicator paradigm is needed. This study suggests that poikilotherms must be considered to be potential primary sources of SFIB in future studies.

Global Distribution of Human-Associated Fecal Genetic Markers in Reference Samples from Six Continents.

Numerous bacterial genetic markers are available for the molecular detection of human sources of fecal pollution in environmental waters. However, widespread application is hindered by a lack of knowledge regarding geographical stability, limiting implementation to a small number of well-characterized regions. This study investigates the geographic distribution of five human-associated genetic markers (HF183/BFDrev, HF183/BacR287, BacHum-UCD, BacH, and Lachno2) in municipal wastewaters (raw and treated) from 29 urban and rural wastewater treatment plants (750-4 400 000 population equivalents) from 13 countries spanning six continents. In addition, genetic markers were tested against 280 human and nonhuman fecal samples from domesticated, agricultural and wild animal sources. Findings revealed that all genetic markers are present in consistently high concentrations in raw (median log10 7.2-8.0 marker equivalents (ME) 100 mL-1) and biologically treated wastewater samples (median log10 4.6-6.0 ME 100 mL-1) regardless of location and population. The false positive rates of the various markers in nonhuman fecal samples ranged from 5% to 47%. Results suggest that several genetic markers have considerable potential for measuring human-associated contamination in polluted environmental waters. This will be helpful in water quality monitoring, pollution modeling and health risk assessment (as demonstrated by QMRAcatch) to guide target-oriented water safety management across the globe.