Follow Up Care After Penile Sparing Surgery for Penile Cancer: Current Perspectives.

Penile cancer (PeCa) is a rare urologic tumor worldwide. In 2024, 2100 new cases and 500 deaths are estimated in the United States. Radical surgery via total penectomy has historically been the cornerstone of treatment, since it provides excellent long-term oncological control. The rationale of surgery for penile cancer was to achieve a 2 cm macroscopic surgical margin that is historically advocated to reduce recurrences. Over time, numerous studies have demonstrated that resection margin status does not affect patients' survival. Different penile-sparing techniques are currently recommended in the European Association of Urology-American Society of Clinical Oncology (EAU-ASCO) guidelines for the treatment of localized primary PeCa. Centralization of care could yield multiple benefits, including improved disease awareness, higher rates of penile-sparing surgery, enhanced detection rates, increased utilization of less invasive lymph node staging techniques, enhanced quality of specialized histopathological examinations, and the establishment of specialized multidisciplinary teams. Compared to more aggressive treatments, the higher recurrence rates after penile-sparing surgery do not hamper neither the metastasis-free survival nor the overall survival. Repeated penile-sparing surgery could be considered for selected cases. The psychological impact of penile cancer is not negligible since the perceived loss of masculinity might adversely affect mental health and overall well-being. Quality of life may be compromised by sexual and urinary dysfunction which may be the result either of the loss of penile tissue or the psychological status of the patient. It is of utmost importance to offer rehabilitative treatment as sexual therapy, physical therapy, occupational therapy, family and peer counseling.

Living Donor Nephrectomy: Analysis of Trends and Outcomes From a Contemporary National Dataset.

OBJECTIVE: To analyze the temporal trends and perioperative and long-term outcomes of living donor kidney nephrectomy in the United States. METHODS: The PearlDiverTM Mariner database (Pearl-Diver Technologies, Colorado Springs, CO, USA) was used for our retrospective analysis. The data were identified using ICD-9/10 codes, as well as CPT codes. Continuous and categorical variables were compared using 2-sided tests. Multivariate logistic regression analysis was conducted to identify predictors of 5-year ESRD. RESULTS: A total of 6333 patients were identified (median age 54, IQR 46-62 years) from 2010 to April 2022. A greater percentage of living donor nephrectomies were performed by general surgeons (56.1%), followed by transplant surgeons (16.5%) and urologists (14.7%). Unfortunately, physician specialty was not reported for the remaining patients. The MIS exceeded open surgery in each specialty group and inpatient setting. The significant predictors of ESRD were male, preoperative DM and hypertension, tobacco smoking, perioperative AKI and younger age at the time of kidney donation. CONCLUSION: MIS represents the main surgical approach for organ procurement. A meticulous selection process for donors and subsequent close monitoring are necessary to minimize the putative consequences of donor nephrectomy.

Can nutraceuticals counteract the detrimental effects of the environment on male fertility? A parallel systematic review and expert opinion.

INTRODUCTION: Male fertility relies on a complex physiology that may be negatively influenced by lifestyle, diet, and environment. The beneficial effect of nutraceuticals on male fertility is a debated claim. The aim of this study was to assess if the positive effect of nutraceuticals can counteract the negative effects of the environment on male fertility. EVIDENCE ACQUISITION: PubMed®/MEDLINE®, Embase and Cochrane Database were searched (September-October 2023), along with crosschecking of references and search for ongoing studies of the effects of the environment and nutraceuticals on male fertility, in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). EVIDENCE SYNTHESIS: Several environmental factors such as microplastic and other endocrine-disrupting chemicals and climate changes may affect the sperm quality in terms of reduction of sperm count number, mobility and altered morphology and thereby reduce male fertility. On the other hand, new evidence demonstrates that a balanced diet rich in antioxidants and essential nutrients, together with minimized exposure to environmental toxins, may improve male fertility and reproductive health. Several nutraceutical compounds proved a protective role against negative environmental effects on male fertility. CONCLUSIONS: Available evidence confirms that the environment may negatively impact male fertility, and this impact is estimated to rise in the forthcoming years. On the other hand, new data indicate that nutraceuticals may have a protective role against the negative impact of environmental factors on male fertility. The need for future studies to monitor and explore these aspects of men's health cannot be underestimated.

Partial nephrectomy in elderly patients: a systematic review and analysis of comparative outcomes.

PURPOSE: The management of renal masses in the elderly population is particularly challenging, as these patients are often more frail and potentially more susceptible to surgical morbidity. This review aims to provide a comprehensive analysis of the outcomes of partial nephrectomy (PN) for treating renal masses in elderly individuals. METHODS: A systematic electronic literature search was conducted in May 2024 using the Medline (via PubMed) database by searching publications up to April 2024. The population, intervention, comparator, and outcome (PICO) model defined study eligibility. Studies were deemed eligible if assessing elderly patients (aged 70 years or older) (P) undergoing PN (I) with or without comparison between a different population (non-elderly) or a different treatment option (radical nephrectomy, ablation or active surveillance) (C) evaluating surgical, functional, and oncological outcomes (O). RESULTS: A total of 23 retrospective studies investigating the role of PN in elderly patients were finally included. PN emerged as a safe procedure also for older patients, demonstrating good outcomes. Preoperative evaluation of frailty status emerged to be paramount. Age alone was discredited as the sole reason to reject the use of PN. The main limitation is the retrospective nature of included studies and the lack of the assessment of elderly patients' frailty. CONCLUSIONS: The surgical treatment of renal masses in older patients is a challenging scenario. PN should be chosen over RN whenever possible since it can better preserve renal function. The use of minimally invasive techniques should be favored in this extremely fragile group of patients.

Safety and efficacy of tixagevimab/cilgavimab for pre-exposure prophylaxis in kidney transplant recipients: a multicenter retrospective cohort study.

BACKGROUND: Immunocompromised patients show an impaired vaccine response and remain at high risk of severe COVID-19, despite vaccination. Neutralizing monoclonal antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed for prophylaxis and treatment. The combination tixagevimab/cilgavimab (AZD7442) has been authorized for emergency use as pre-exposure prophylaxis for COVID-19, but data on safety and efficacy in kidney transplant recipients during the Omicron period are limited. METHODS: We conducted a multicenter retrospective cohort study including 253 kidney transplant recipients, of whom 98 were treated with tixagevimab/cilgavimab 150 mg/150 mg and 155 who received only four doses of the BNT162b2 mRNA vaccine. RESULTS: Only 13.3% of patients developed SARS-CoV-2 infection after the administration of tixagevimab/cilgavimab; in comparison, 34.2% of patients had been infected after the fourth dose of vaccine (p = 0.00013). Most infected patients in the AZD7442 group remained asymptomatic (92.3% vs 54.7%), 7.7% had mild symptoms and none had severe disease, need for hospitalization or died, while in the control group, 9.4% of patients had moderate or severe disease (p = 0.04). Using Kaplan-Meier curves we demonstrated that the controls presented early infection compared to the AZD7442 group (p = 0.000014). No changes in eGFR or proteinuria, assessed before and after the administration, were observed. CONCLUSIONS: In conclusion, our study showed that tixagevimab/cilgavimab 150/150 mg is effective and safe in preventing infection and severe disease when administered to patients with weak or no response to COVID-19 vaccine.

Transperineal laser ablation of the prostate as a treatment for benign prostatic hyperplasia and prostate cancer: The results of a Delphi consensus project.

Objective: To evaluate transperineal laser ablation (TPLA) with Echolaser® (Echolaser® TPLA, Elesta S.p.A., Calenzano, Italy) as a treatment for benign prostatic hyperplasia (BPH) and prostate cancer (PCa) using the Delphi consensus method. Methods: Italian and international experts on BPH and PCa participated in a collaborative consensus project. During two rounds, they expressed their opinions on Echolaser® TPLA for the treatment of BPH and PCa answering online questionnaires on indications, methodology, and potential complications of this technology. Level of agreement or disagreement to reach consensus was set at 75%. If the consensus was not achieved, questions were modified after each round. A final round was performed during an online meeting, in which results were discussed and finalized. Results: Thirty-two out of forty invited experts participated and consensus was reached on all topics. Agreement was achieved on recommending Echolaser® TPLA as a treatment of BPH in patients with ample range of prostate volume, from <40 mL (80%) to >80 mL (80%), comorbidities (100%), antiplatelet or anticoagulant treatment (96%), indwelling catheter (77%), and strong will of preserving ejaculatory function (100%). Majority of respondents agreed that Echolaser® TPLA is a potential option for the treatment of localized PCa (78%) and recommended it for low-risk PCa (90%). During the final round, experts concluded that it can be used for intermediate-risk PCa and it should be proposed as an effective alternative to radical prostatectomy for patients with strong will of avoiding urinary incontinence and sexual dysfunction. Almost all participants agreed that the transperineal approach of this organ-sparing technique is safer than transrectal and transurethral approaches typical of other techniques (97% of agreement among experts). Pre-procedural assessment, technical aspects, post-procedural catheterization, pharmacological therapy, and expected outcomes were discussed, leading to statements and recommendations. Conclusion: Echolaser® TPLA is a safe and effective procedure that treats BPH and localized PCa with satisfactory functional and sexual 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.

The Role of MUC1 in Renal Cell Carcinoma.

Mucins are a family of high-molecular-weight glycoproteins. MUC1 is widely studied for its role in distinct types of cancers. In many human epithelial malignancies, MUC1 is frequently overexpressed, and its intracellular activities are crucial for cell biology. MUC1 overexpression can enhance cancer cell proliferation by modulating cell metabolism. When epithelial cells lose their tight connections, due to the loss of polarity, the mucins become dispersed on both sides of the epithelial membrane, leading to an abnormal mucin interactome with the membrane. Tumor-related MUC1 exhibits certain features, such as loss of apical localization and aberrant glycosylation that might cause the formation of tumor-related antigen epitopes. Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies and it is the most common kidney cancer. The exact role of MUC1 in this tumor is unknown. Evidence suggests that it may play a role in several oncogenic pathways, including proliferation, metabolic reprogramming, chemoresistance, and angiogenesis. The purpose of this review is to explore the role of MUC1 and the meaning of its overexpression in epithelial tumors and in particular in RCC.

Sacral Neuromodulation: Device Improvement and Current Applications in Urology.

Sacral neuromodulation (SNM) offers a therapeutic approach to urological patients suffering from idiopathic overactive bladder (OAB) syndrome, with or without incontinence and non-obstructive urinary retention (NOR), who are not responding to or are not compliant with conservative or medical therapies. The exact mechanism of action of SNM is not fully understood but modulation of the spinal cord reflexes and brain networks by peripheral afferents is regarded as the main pathway. Over the years, surgical techniques improved, leading to the development of the modern two-stage implantation technique. The quadripolar lead is positioned percutaneously under fluoroscopy guidance through the third sacral foramen following the trajectory of S3. The procedure can be performed under local or general anesthesia with the patient in prone position. Current applications of sacral neuromodulation in urology are increasing thanks to the recent improvements of the devices that make this a valuable option not only in conditions such as overactive bladder and non-obstructing urinary retention but also neurogenic lower urinary tract dysfunction.

Robot-assisted buccal mucosal graft ureteroplasty for the treatment of proximal ureteral strictures.

The authors describe their initial experience with robot-assisted buccal mucosal graft (BMG) ureteroplasty for the management of proximal ureteral strictures.

Management of Pediatric Urolithiasis in an Italian Tertiary Referral Center: A Retrospective Analysis.

Background and Objectives: In recent years, the prevalence of pediatric urolithiasis has increased in North America and Western countries, though it is endemic in developing countries. The aim of this study is to describe the experience of a tertiary pediatric referral center in the surgical management of pediatric urolithiasis. Materials and Methods: We retrospectively reviewed the experience of patients ≤ 16 years old affected by urinary stones who underwent surgery. Results: From April 2021 to September 2023, 31 pediatric patients underwent surgical procedures for stone diseases at our department: 13 preschool-aged (1-5 years) and 18 school-aged (6-16 years) children. During this period, 12 URSs, 17 RIRSs, and 2 PCNLs were recorded. Five patients had residual fragments at first, so three of them underwent a second endourological lithotripsy (2 RIRSs and 1 URS). Complete clearance was finally achieved in 27 patients. The stone composition was evaluated in 25 cases. Conclusions: Numerous innovations in the surgical treatment of pediatric urolithiasis have resulted from the development of smaller devices and new technology. Our results show how, in experienced centers, retrograde and percutaneous lithotripsy are safe and effective procedures for use in pediatric populations.

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.

Intermediate-term oncological and functional outcomes in prostate cancer patients treated with perineal robot-assisted radical prostatectomy: A single center analysis.

Objective: In the last 10 years, robotic platforms allowed to resume of some alternative surgical approaches, including perineal robot-assisted radical prostatectomy (p-RARP). Herein, we present in detail the oncological and functional outcomes of patients who underwent p-RARP with a median follow-up of 30 months. Methods: Patients presenting low- or intermediate-risk prostate cancer and prostate volume up to 60 mL who underwent p-RARP between November 2018 and November 2022 were selected. Baseline, intraoperative, pathological, and postoperative data were collected and then analyzed. Results: Thirty-seven p-RARP cases were included. Such patients presented mean age of 62 years and a mean Charlson comorbidity index of 4. Body mass index of ≥25 kg/m2 was reported by 24 (64.9%) patients, as well as 7 (18.9%) patients reported a past surgical history. Mean prostate volume and median prostate-specific antigen were 41 mL and 6.2 ng/mL, respectively. The median operative time was 242 min. The positive surgical margin rate was 45.9%. In terms of postoperative complications, 10 patients reported complications with any grade; however, a single case (2.7%) of major (Clavien-Dindo grade ≥3) complication was observed. No patient with biochemical recurrence or distant metastasis was reported at 2 years of follow-up. Recovery of continence rates were 67.6%, 75.7%, and 92.9%, at 6 months, 12 months, and 24 months after surgery, respectively. Conclusion: p-RARP is a challenging but safe minimally invasive approach for selected patients with prostate cancer suitable for radical prostatectomy, showing outstanding functional recovery. Despite positive surgical margin rates being relatively high, no cases of biochemical recurrence or distant metastasis were reported after a median follow-up of 30 months.

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.

Kinetics of humoral immune response and severity of infection after three doses of SARS-CoV-2 mRNA vaccine in a large cohort of kidney transplant recipients.

BACKGROUND: COVID-19 in kidney transplant recipients is associated with high morbidity and mortality. In this study we aimed to evaluate: (i) the seroconversion rate after BNT162b2 (Pfizer-BioNTech) SARS-CoV-2 vaccine, (ii) factors associated with humoral response, (iii) clinical outcome of COVID-19 in kidney transplanted patients. METHODS: We enrolled a cohort of 743 kidney transplant recipients followed up from March 2020 until April 2022. A subset of 336 patients, who received three-doses of SARS-CoV-2 vaccine, was analyzed in terms of kinetics of humoral immune response and compared to a control group of 94 healthcare workers. Antibody response was tested before vaccination (T0), 15 and 90 days after the second dose (T1 and T2), on the day of the third dose (T3) and one month after the third dose (T4). RESULTS: We observed that 66 out of 743 subjects had COVID-19 infection pre-vaccination: 65.2% had severe symptoms, 27.3% were hospitalized (9 deaths), none were asymptomatic. After three doses, 51 patients had COVID-19 infection, 60.8% were asymptomatic, 27.5% reported mild symptoms, 3.9% showed severe symptoms, 7.8% were hospitalized (2 deaths). In the subset of 336 vaccinated patients, an antibody level > 0.8 U/ml was detected at T1, that increased at T2 and T3, peaking at T4. Independent factors associated with a negative antibody titer at T4 were decreasing estimated glomerular filtration rate, time from transplantation, and antimetabolites (all p < 0.001) and age (p = 0.007). CONCLUSIONS: The kinetics of humoral response after three doses of vaccine in kidney transplant patients is characterized by a late but effective immune response against SARS-CoV-2, reducing morbidity and mortality.

Cellular and Molecular Players in the Tumor Microenvironment of Renal Cell Carcinoma.

Globally, clear-cell renal cell carcinoma (ccRCC) represents the most prevalent type of kidney cancer. Surgery plays a key role in the treatment of this cancer, although one third of patients are diagnosed with metastatic ccRCC and about 25% of patients will develop a recurrence after nephrectomy with curative intent. Molecular-target-based agents, such as tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs), are recommended for advanced cancers. In addition to cancer cells, the tumor microenvironment (TME) includes non-malignant cell types embedded in an altered extracellular matrix (ECM). The evidence confirms that interactions among cancer cells and TME elements exist and are thought to play crucial roles in the development of cancer, making them promising therapeutic targets. In the TME, an unfavorable pH, waste product accumulation, and competition for nutrients between cancer and immune cells may be regarded as further possible mechanisms of immune escape. To enhance immunotherapies and reduce resistance, it is crucial first to understand how the immune cells work and interact with cancer and other cancer-associated cells in such a complex tumor microenvironment.

Three years outcomes of transperineal laser ablation of the prostate.

BACKGROUND: Ultra-minimally Invasive Surgical Techniques (uMISTs) play an increasingly significant role in treating benign prostatic obstruction (BPO) as an alternative to both medical therapy and surgery. Transperineal laser ablation of the prostate (TPLA) is an uMIST that has shown its efficacy in symptom relief and improvement of urodynamic parameters while sparing ejaculatory function and having a low risk of complications. This is the 3-year follow-up of a pilot study on TPLA. METHODS: TPLA was performed using the SoracteLite™ system. It consists of ablating prostate tissue through a diode laser, eventually causing prostate volume reduction. We recorded International Prostate Symptom Score (IPSS), uroflowmetry parameters, the Male Sexual Health Questionnaire (MSHQ-EjD), and prostate volume at baseline and after 3 years. The Wilcoxon Test was employed to compare continuous variables. RESULTS: Twenty men completed a 3-year follow-up after TPLA. The median prostate volume was 41.5 mL (IQR: 40.0-54.3). Preoperative median IPSS, Qmax, and MSHQ-EjD were 18 (IQR: 16-21), 8.8 mL/s (IQR: 7.8-10.8), and 4 (IQR: 3-8). TPLA showed significant improvement in IPSS (-37.2%; P<0.01) and Qmax (45.8%; P<0.01); median MSHQ-EjD improvement was by 60% (P<0.01) and median prostate volume reduction was by -20.4% (P<0.01). CONCLUSIONS: This analysis shows that TPLA maintains satisfactory results within 3 years. Therefore, TPLA confirms its role in the treatment of patients unsatisfied or intolerant to oral therapies but not eligible for surgery to avoid impact on sexual function or due to anesthesiologic contraindications.

Immune Checkpoint Inhibitors in Renal Cell Carcinoma: Molecular Basis and Rationale for Their Use in Clinical Practice.

Renal cell carcinoma (RCC) is the seventh most common cancer in men and the ninth most common cancer in women worldwide. There is plenty of evidence about the role of the immune system in surveillance against tumors. Thanks to a better understanding of immunosurveillance mechanisms, immunotherapy has been introduced as a promising cancer treatment in recent years. Renal cell carcinoma (RCC) has long been thought chemoresistant but highly immunogenic. Considering that up to 30% of the patients present metastatic disease at diagnosis, and around 20-30% of patients undergoing surgery will suffer recurrence, we need to identify novel therapeutic targets. The introduction of immune checkpoint inhibitors (ICIs) in the clinical management of RCC has revolutionized the therapeutic approach against this tumor. Several clinical trials have shown that therapy with ICIs in combination or ICIs and the tyrosine kinase inhibitor has a very good response rate. In this review article we summarize the mechanisms of immunity modulation and immune checkpoints in RCC and discuss the potential therapeutic strategies in renal cancer treatment.

MUC1 Expression Affects the Immunoflogosis in Renal Cell Carcinoma Microenvironment through Complement System Activation and Immune Infiltrate Modulation.

Mucin1 (MUC1), a glycoprotein associated with an aggressive cancer phenotype and chemoresistance, is aberrantly overexpressed in a subset of clear cell renal cell carcinoma (ccRCC). Recent studies suggest that MUC1 plays a role in modulating cancer cell metabolism, but its role in regulating immunoflogosis in the tumor microenvironment remains poorly understood. In a previous study, we showed that pentraxin-3 (PTX3) can affect the immunoflogosis in the ccRCC microenvironment by activating the classical pathway of the complement system (C1q) and releasing proangiogenic factors (C3a, C5a). In this scenario, we evaluated the PTX3 expression and analyzed the potential role of complement system activation on tumor site and immune microenvironment modulation, stratifying samples in tumors with high (MUC1H) versus tumors with low MUC1 expression (MUC1L). We found that PTX3 tissue expression was significantly higher in MUC1H ccRCC. In addition, C1q deposition and the expressions of CD59, C3aR, and C5aR were extensively present in MUC1H ccRCC tissue samples and colocalized with PTX3. Finally, MUC1 expression was associated with an increased number of infiltrating mast cells, M2-macrophage, and IDO1+ cells, and a reduced number of CD8+ T cells. Taken together, our results suggest that expression of MUC1 can modulate the immunoflogosis in the ccRCC microenvironment by activating the classical pathway of the complement system and regulating the immune infiltrate, promoting an immune-silent microenvironment.