The Cavernous Nerve Injury Rat Model: A Pictorial Essay on Post-Radical Prostatectomy Erectile Dysfunction Research.

Understanding and addressing post-radical prostatectomy (RP) erectile dysfunction (ED) is of paramount importance for clinicians. Cavernous nerve (CN) injury rat model studies have provided consistently promising experimental data regarding regaining erectile function (EF) after nerve damage-induced ED. However, these findings have failed to translate efficiently into clinical practice, with post-RP ED therapeutic management remaining cumbersome and enigmatic. This disparity highlights the need for further standardization and optimization of the elaborate surgical preparation protocols and multifaceted reporting parameters involved in reliable CN injury rat model experimentation. Even so, despite its technical complexity, this animal model remains instrumental in exploring the functional implications of RP, i.e., surgical lesions of the neurovascular bundles (NVBs). Herein, besides cavernous nerve (CN) dissection, injury, and electrostimulation, multiple pressure measurements, i.e., mean arterial pressure (MAP) and intra-cavernosal pressure (ICP), must also be achieved. A transverse cervical incision allows for carotid artery cannulation and MAP measurements. Conversely, ICP measurements entail circumcising the penis, exposing the ischiocavernous muscle, and inserting a needle into the corporal body. Finally, using an abdominal incision, the prostate is revealed, and the major pelvic ganglia (MPG) and CNs are dissected bilaterally. Specific surgical techniques are used to induce CN injuries. Herein, we provide a narrative and illustrative overview regarding these complex experimental procedures and their particular requirements, reflecting on current evidence and future research perspectives.

Contemporary Biomarkers for Renal Transplantation: A Narrative Overview.

Renal transplantation (RT) is the preferred treatment for end-stage renal disease. However, clinical challenges persist, i.e., early detection of graft dysfunction, timely identification of rejection episodes, personalization of immunosuppressive therapy, and prediction of long-term graft survival. Biomarkers have emerged as valuable tools to address these challenges and revolutionize RT patient care. Our review synthesizes the existing scientific literature to highlight promising biomarkers, their biological characteristics, and their potential roles in enhancing clinical decision-making and patient outcomes. Emerging non-invasive biomarkers seemingly provide valuable insights into the immunopathology of nephron injury and allograft rejection. Moreover, we analyzed biomarkers with intra-nephron specificities, i.e., glomerular vs. tubular (proximal vs. distal), which can localize an injury in different nephron areas. Additionally, this paper provides a comprehensive analysis of the potential clinical applications of biomarkers in the prediction, detection, differential diagnosis and assessment of post-RT non-surgical allograft complications. Lastly, we focus on the pursuit of immune tolerance biomarkers, which aims to reclassify transplant recipients based on immune risk thresholds, guide personalized immunosuppression strategies, and ultimately identify patients for whom immunosuppression may safely be reduced. Further research, validation, standardization, and prospective studies are necessary to fully harness the clinical utility of RT biomarkers and guide the development of targeted therapies.

Rats, Neuregulins and Radical Prostatectomy: A Conceptual Overview.

In the contemporary era of early detection, with mostly curative initial treatment for prostate cancer (PC), mortality rates have significantly diminished. In addition, mean age at initial PC diagnosis has decreased. Despite technical advancements, the probability of erectile function (EF) recovery post radical prostatectomy (RP) has not significantly changed throughout the last decade. Due to virtually unavoidable intraoperative cavernous nerve (CN) lesions and operations with younger patients, post-RP erectile dysfunction (ED) has now begun affecting these younger patients. To address this pervasive limitation, a plethora of CN lesion animal model investigations have analyzed the use of systemic/local treatments for EF recovery post-RP. Most promisingly, neuregulins (NRGs) have demonstrated neurotrophic effects in both neurodegenerative disease and peripheral nerve injury models. Recently, glial growth factor 2 (GGF2) has demonstrated far superior, dose-dependent, neuroprotective/restorative effects in the CN injury rat model, as compared to previous therapeutic counterparts. Although potentially impactful, these initial findings remain limited and under-investigated. In an effort to aid clinicians, our paper reviews post-RP ED pathogenesis and currently available therapeutic tools. To stimulate further experimentation, a standardized preparation protocol and in-depth analysis of applications for the CN injury rat model is provided. Lastly, we report on NRGs, such as GGF2, and their potentially revolutionary clinical applications, in hopes of identifying relevant future research directions.

Contemporary Clinical Definitions, Differential Diagnosis, and Novel Predictive Tools for Renal Cell Carcinoma.

Despite significant progress regarding clinical detection/imaging evaluation modalities and genetic/molecular characterization of pathogenesis, advanced renal cell carcinoma (RCC) remains an incurable disease and overall RCC mortality has been steadily rising for decades. Concomitantly, clinical definitions have been greatly nuanced and refined. RCCs are currently viewed as a heterogeneous series of cancers, with the same anatomical origin, but fundamentally different metabolisms and clinical behaviors. Thus, RCC pathological diagnosis/subtyping guidelines have become increasingly intricate and cumbersome, routinely requiring ancillary studies, mainly immunohistochemistry. Meanwhile, RCC-associated-antigen targeted systemic therapy has been greatly diversified and emerging, novel clinical applications for RCC immunotherapy have already reported significant survival benefits, at least in the adjuvant setting. Even so, systemically disseminated RCCs still associate very poor clinical outcomes, with currently available therapeutic modalities only being able to prolong survival. In lack of a definitive cure for advanced RCCs, integration of the amounting scientific knowledge regarding RCC pathogenesis into RCC clinical management has been paramount for improving patient outcomes. The current review aims to offer an integrative perspective regarding contemporary RCC clinical definitions, proper RCC clinical work-up at initial diagnosis (semiology and multimodal imaging), RCC pathological evaluation, differential diagnosis/subtyping protocols, and novel clinical tools for RCC screening, risk stratification and therapeutic response prediction.

Evaluating Established Roles, Future Perspectives and Methodological Heterogeneity for Wilms' Tumor 1 (WT1) Antigen Detection in Adult Renal Cell Carcinoma, Using a Novel N-Terminus Targeted Antibody (Clone WT49).

Renal cell carcinoma (RCC) is arguably the deadliest form of genitourinary malignancy and is nowadays viewed as a heterogeneous series of cancers, with the same origin but fundamentally different metabolisms and clinical behaviors. Immunohistochemistry (IHC) is increasingly necessary for RCC subtyping and definitive diagnosis. WT1 is a complex gene involved in carcinogenesis. To address reporting heterogeneity and WT1 IHC standardization, we used a recent N-terminus targeted monoclonal antibody (clone WT49) to evaluate WT1 protein expression in 56 adult RCC (aRCC) cases. This is the largest WT1 IHC investigation focusing exclusively on aRCCs and the first report on clone WT49 staining in aRCCs. We found seven (12.5%) positive cases, all clear cell RCCs, showing exclusively nuclear staining for WT1. We did not disregard cytoplasmic staining in any of the negative cases. Extratumoral fibroblasts, connecting tubules and intratumoral endothelial cells showed the same exclusively nuclear WT1 staining pattern. We reviewed WT1 expression patterns in aRCCs and the possible explanatory underlying metabolomics. For now, WT1 protein expression in aRCCs is insufficiently investigated, with significant discrepancies in the little data reported. Emerging WT1-targeted RCC immunotherapy will require adequate case selection and sustained efforts to standardize the quantification of tumor-associated antigens for aRCC and its many subtypes.

The impact of tiredness on virtual reality robotic surgical skills.

INTRODUCTION: The effect of tiredness has been proved for the surgeons' musculature performing laparoscopic or robotic procedures (physical stress). Mental stress after robotic surgery has been reported as well. It is still unclear how much the surgical skills are altered and which types of skills are more affected at the final steps of long, complex robotic surgical procedures. AIM: To evaluate to what extent the surgeon's skills are influenced by long procedures, using the objective assessment of different surgical skills by a virtual reality robotic simulator. MATERIAL AND METHODS: Fifteen surgeons were asked to perform a continuous 4 h virtual robotic surgical simulator training session. At the beginning of simulator training and at the end of each of the 4 h of training, three exercises of increasing difficulty were selected to be performed in order to assess the surgeons' skills. RESULTS: There were statistically significant differences between the initial and final overall scores for all the three exercises, the final outcomes being inferior. The specific metrics for each exercise slightly improved within 1 h from the beginning and thereafter decreased to a statistically significantly inferior value. CONCLUSIONS: The specific metrics on the virtual reality robotic surgical simulator were altered after a 4-hour console training period. Further larger and more complex studies are necessary to evaluate the translation from the simulator to real-life robotic surgery.

Ethical, legal and clinical aspects of live surgery in urology - contemporary issues and a glimpse of the future.

Beside dry and wet lab training, simulators, video tapes, fellowships and clinical visits, live surgery has gained popularity during the last years, being an attraction point at large scientific meetings and at postgraduate courses as well. This type of surgical training raises both ethical and legal issues. Thus, there are professional societies that have banned such meetings, mainly due to safety reasons for the patient. The current article aims to identify and to discuss ethical and legal issues related to the topic, advantages, disadvantages and weak points of this emerging challenge for modern medicine, trying to analyze the issues from all relevant points of view: those of the patient, the surgeon and the session attendant.

Does previous open surgical experience have any influence on robotic surgery simulation exercises?

INTRODUCTION: Within the last years, there has been a trend in many hospitals to switch their surgical activity from open/laparoscopic procedures to robotic surgery. Some open surgeons have been shifting their activity to robotic surgery. It is still unclear whether there is a transfer of open surgical skills to robotic ones. AIM: To evaluate whether such transfer of skills occurs and to identify which specific skills are more significantly transferred from the operative table to the console. MATERIAL AND METHODS: Twenty-five volunteers were included in the study, divided into 2 groups: group A (15 participants) - medical students (without any surgical experience in open, laparoscopic or robotic surgery); and group B (10 participants) - surgeons with exclusively open surgical experience, without any previous laparoscopic or robotic experience. Participants were asked to complete 3 robotic simulator console exercises structured from the easiest one (Peg Board) to the toughest one (Sponge Suture). Overall scores for each exercise as well as specific metrics were compared between the two groups. RESULTS: There were no significant differences between overall scores of the two groups for the easiest task. Overall scores were better for group B as the exercises got more complex. For the intermediate and high-difficulty level exercises, most of the specific metrics were better for group B, with the exception of the working master space item. CONCLUSIONS: Our results suggest that the open surgical skills transfer to robotic skills, at least for the very beginning of the training process.