Evidence of restorative therapies in the treatment of Peyronie disease: A narrative review

ABSTRACT Objective: To describe the evidence of Platelet Rich Plasma (PRP), Stem cells therapy (SCT) and Extracorporeal shockwave therapy (ESWL) for the treatment of Peyronies disease (PD), including information from the main urological society guidelines. Materials and Methods: A literature review of PubMed articles published between 2000 and 2023 was conducted, utilizing keywords such as "Peyronie's Disease", "Penile curvature", "Platelet Rich Plasma", "Stem cells", and "Extracorporeal shockwave therapy". Only full-text articles in English were included, excluding case reports and opinions. Results: A considerable number of clinical trials were conducted using PRP penile injections for therapy of PD, showing reduction of curvature, plaque size and improvement in quality of life. Preclinical studies in rats have shown the potential benefit of adipose-derived stem cells, with improvements in erectile function and fibrosis. Human studies with mesenchymal stem cells demonstrated promising results, with reduction of curvature and plaque size. ESWL effects on PD were investigated in randomized clinical trials and demonstrated no significant impact in curvature or plaque size, but reasonable effect on pain control. Conclusion: Restorative therapies has emerged as an innovative treatment option for PD and the results from current studies appear to be promising and demonstrated good safety profile. Unfortunately, due to scarce evidence, PRP and SCT are still considered experimental by American Urological Association (AUA) and European Association of Urology (EAU) guidelines. ESWT is recommended, by the same guidelines, for pain control only. More high-quality studies with long-term follow-up outcomes are needed to evaluate efficacy and reproducibility of those therapies.

Development of nerves and vessels in the penis during the human fetal period

ABSTRACT Introduction: Although nerves and vessels of the penis play important role in erection, there are few studies on their development in human fetus. Therefore, the objective of the present study is to analyze, quantitatively, in the corpora cavernosa and corpus spongiosum, the development of the nerves and vessels in the fetal penis at different gestational ages. Material and Methods: Fifty-six fresh, macroscopically normal human fetuses aged from 13 to 36 weeks post-conception (WPC) were used. Gestational age was determined by the foot length criterion. Penises were immediately fixed in 10% formalin, and routinely processed for paraffin embedding, after which tissue sections from the mid-shaft were obtained. We used immunohistochemical staining to analyze the nerves and vessels in the corpus cavernous and in the corpus spongiosum. These elements were identified and quantified as percentage by using the Image-J software. Results: The quantitative analysis showed that the percentage of nerves varied from 3.03% to 20.35% in the corpora cavernosa and from 1.89% to 23.88% in the corpus spongiosum. The linear regression analysis indicated that nerves growth (incidence) in the corpora cavernosa and corpus spongiosum correlated significantly and positively with fetal age (r2=0.9421, p<0.0001) and (r2=0.9312, p<0.0001), respectively, during the whole fetal period studied. Also, the quantitative analysis showed that the percentage of vessels varies from 2.96% to 12.86% in the corpora cavernosa and from 3.62% to 14.85% in the corpus spongiosum. The linear regression analysis indicated that vessels growth (appearance) in the corpora cavernosa and corpus spongiosum correlated significantly and positively with fetal age (r2=0.8722, p<0.0001) and (r2=0.8218, p<0.0001), respectively, during the whole fetal period studied. In addition, the linear regression analysis demonstrated a more intense growth rate of nerves in the corpus spongiosum during the 2nd trimester of gestation, when compared with nerves in the corpora cavernosa. In addition, the linear regression analysis demonstrated a more intense growth rate of vessels in the corpus spongiosum when compared with the corpora cavernosa, during the whole fetal period studied. Conclusions: In the fetal period, the human penis undergoes major developmental changes, notably in the content and distribution of nerves and vessels. We found strong correlation between nerves and vessels growth (amount) with fetal age, both in the corpora cavernosa and corpus spongiosum. There is significant greater proportional number of nerves than vessels during the whole fetal period studied. Also, nerves and vessels grow in a more intense rate than that of the corpora cavernosa and corpus spongiosum areas.

Comparative Study of Gleason 7 (3+4) and (4+3) Prostatic Adenocarcinomas with Prog-nostic Criteria and Immunohistochemical Profiles of AMACR, PSA and Ki-67.

BACKGROUND: To compare Gleason 7 (3+4) and (4+3) prostatic adenocarcinoma (PC) with different prognostic criteria through immunohistochemical analysis with anti-PSA, anti-Ki 67 and anti-AMARC antibodies. METHODS: We analyzed 221 surgical specimens from patients between 40 and 86 years-old (mean=63) with PC. The immunohistochemical study was performed with anti-PSA, anti-Ki 67 and anti-AMARC. The microscopic fields were photographed with an Olympus DP70 digital camera coupled to an Olympus BX51 microscope and archived in TIFF. Proportion and intensity criteria were used to quantify the anti-PSA antibody and for the anti-Ki 67 antibody, the quantification by similarity of this antibody in breast carcinomas. Anti-AMACR protein expression was based on four scores: negative, weak, moderate and strong. The statistical analysis was performed with the Graph Pad Prism 5 program. RESULTS: In the Gleason score 7 (3+4) we had 91.72% in pT2 and 8.27% in the pT3 group; 8.27% recurrences, of which 90.90% in the pT2 group. In the Gleason score 7 (4+3) we had 77.27% in the pT2 group and 22.72% in the pT3 group and 10.22% of relapses, of which 66.66% in the pT2 group and 33.33% in the pT3 group. In 6.81% of cases there was an increase in the anti-Ki 67 index and in 2.27% of the cases, there was an increase in the immunoexpression of anti-p53 when comparing Gleason score 7 (3+4) with Gleason score 7 (4+3). CONCLUSION: Our study confirmed differences in the Gleason score 7 (3+4) and Gleason score 7 (4+3) of PC when comparing prognostic criteria. Anti-Ki 67 and anti-PSA antibody immunostaining showed a positive correlation as the Gleason score 7 increased from (3+4) to (4+3).

Prospective results of the minimally invasive laser enucleation of the prostate (MiLEP).

BACKGROUND: The objective of the present study is to prospectively analyze the prostate enucleation procedure with Holmium Laser using the minimally invasive technique (MiLEP), comparing the outcomes and their variables pre- and postoperatively. METHODS: We studied men aged 40 years or over, with prostate volumes greater than or equal to 35 cm³ with lower urinary tract symptoms due to BPH. We performed flowmetry and administered the IPSS questionnaire before and 6 months after the MiLEP procedure. The patients were operated on with a 60 W Holmium Laser (Cyber-Ho Quanta System®) using 54 W of power (energy 1.8 J and frequency of 30 Hz). Enucleation was performed using the en bloc technique with early sphincter release. After enucleation, the tissue was morcellated using a 22 Fr morcescope (RZ-Medizintechnik GmbH, Tuttlingen, Germany) and Piranha (Richard Wolf) morcellator. The final Hemostasis after morcelation was made using laser with 30wW power, energy at 1,0 joules and frequency at 30 Hertz. Student's T test and Man-Whitney was used to statistical analysis (p < 0.05). RESULTS: After selection we submitted 73 patients (mean age= 68.2 years) to MiLEP procedure with a follow up of 6 months. The prostate volume presented an average of 94.53 cm³ (65 to 112 cm³, SD = 5.363) preoperatively. The urinary continence rate after the procedure was greater than 95% after 1 week and 99% in the 1st month. All patients were continent after 6 months. The IPSS questionnaire before (mean = 21.18 points/SD = 6.557) and after (mean = 7.92 points/SD = 2.408) the MiLEP had statistical significance (p < 0.001). The flowmetry(ml/s) before (9.02/SD = 2.842) and after (21.07/SD = 6.228) the MiLEP had statistical significance (p < 0.001). The average time of the procedure was 78.5 min and the bladder catheter was removed after 18 h in mean. In 4 patients (5.8%) we observed hematuria and in 1 case (1.47%) the patient needs urinary catheterization. CONCLUSION: MiLEP is a safe and effective procedure, with significant improvement in urinary flow and symptoms in the short term. Although the results of this study were satisfactory and the urinary incontinence rate was lower compared to HoLEP data found in the literature, multicenter studies with longer follow-up are needed to confirm these findings.

A complete year of urology residency training under COVID-19: impact on education and health.

OBJECTIVES: To evaluate the impact of COVID-19 pandemics on clinical and surgical practice, educational activities, health and lifestyle behavior of Brazilian urology residents after 1 year of socio-economic restrictions. MATERIALS AND METHODS: An electronic survey was e-mailed to all postgraduate (PG) students registered by the Brazilian Society of Urology. The survey inclu-ded an assessment of socio-demographic, clinical practice, educational, health-related and behavior parameters. We also evaluated which subareas of urology were predominantly affected. A similar survey was adapted and sent to the directors of all urology residency programs. RESULTS: COVID-19 pandemic has severely impacted the clinical, surgical, and educational activities of urology residents in Brazil. Urology residents reported >50% decrease in multiple surgical modalities. We highlight kidney transplantation surgeries (66.2%), minor surgeries (62.3%), endoscopic surgeries (42.6%) and reconstructive surgeries (38.8%). This could represent a critical skills gap that residents may face beyond the COVID-19 pandemic. Furthermore, PG students faced stressful situations that caused worsening of mental and physical health, such as getting redirected to assistance of COVID-19 patients (66.9%), and high rate of infection by SARS-CoV-2 (58.2%). CONCLUSIONS: The COVID-19 pandemic has severely impacted the clinical, surgical, and educational activities of urology residents in Brazil. This could represent a critical skills gap that residents may face beyond the COVID-19 pandemic. PG students faced stressful situations that caused worsening of mental and physical health such as redirection to assistance of COVID-19 patients, concern about their own contamination and of family members.

Development of nerves and vessels in the penis during the human fetal period.

INTRODUCTION: Although nerves and vessels of the penis play important role in erection, there are few studies on their development in human fetus. Therefore, the objective of the present study is to analyze, quantitatively, in the corpora cavernosa and corpus spongiosum, the development of the nerves and vessels in the fetal penis at different gestational ages. MATERIAL AND METHODS: Fifty-six fresh, macroscopically normal human fetuses aged from 13 to 36 weeks post-conception (WPC) were used. Gestational age was determined by the foot length criterion. Penises were immediately fixed in 10% formalin, and routinely processed for paraffin embedding, after which tissue sections from the mid-shaft were obtained. We used immunohistochemical staining to analyze the nerves and vessels in the corpus cavernous and in the corpus spongiosum. These elements were identified and quantified as percentage by using the Image-J software. RESULTS: The quantitative analysis showed that the percentage of nerves varied from 3.03% to 20.35% in the corpora cavernosa and from 1.89% to 23.88% in the corpus spongiosum. The linear regression analysis indicated that nerves growth (incidence) in the corpora cavernosa and corpus spongiosum correlated significantly and positively with fetal age (r2=0.9421, p<0.0001) and (r2=0.9312, p<0.0001), respectively, during the whole fetal period studied. Also, the quantitative analysis showed that the percentage of vessels varies from 2.96% to 12.86% in the corpora cavernosa and from 3.62% to 14.85% in the corpus spongiosum. The linear regression analysis indicated that vessels growth (appearance) in the corpora cavernosa and corpus spongiosum correlated significantly and positively with fetal age (r2=0.8722, p<0.0001) and (r2=0.8218, p<0.0001), respectively, during the whole fetal period studied. In addition, the linear regression analysis demonstrated a more intense growth rate of nerves in the corpus spongiosum during the 2nd trimester of gestation, when compared with nerves in the corpora cavernosa. In addition, the linear regression analysis demonstrated a more intense growth rate of vessels in the corpus spongiosum when compared with the corpora cavernosa, during the whole fetal period studied. CONCLUSIONS: In the fetal period, the human penis undergoes major developmental changes, notably in the content and distribution of nerves and vessels. We found strong correlation between nerves and vessels growth (amount) with fetal age, both in the corpora cavernosa and corpus spongiosum. There is significant greater proportional number of nerves than vessels during the whole fetal period studied. Also, nerves and vessels grow in a more intense rate than that of the corpora cavernosa and corpus spongiosum areas.

Evidence of restorative therapies in the treatment of Peyronie disease: A narrative review.

OBJECTIVE: To describe the evidence of Platelet Rich Plasma (PRP), Stem cells therapy (SCT) and Extracorporeal shockwave therapy (ESWL) for the treatment of Peyronies disease (PD), including information from the main urological society guidelines. MATERIALS AND METHODS: A literature review of PubMed articles published between 2000 and 2023 was conducted, utilizing keywords such as "Peyronie's Disease", "Penile curvature", "Platelet Rich Plasma", "Stem cells", and "Extracorporeal shockwave therapy". Only full-text articles in English were included, excluding case reports and opinions. RESULTS: A considerable number of clinical trials were conducted using PRP penile injections for therapy of PD, showing reduction of curvature, plaque size and improvement in quality of life. Preclinical studies in rats have shown the potential benefit of adipose-derived stem cells, with improvements in erectile function and fibrosis. Human studies with mesenchymal stem cells demonstrated promising results, with reduction of curvature and plaque size. ESWL effects on PD were investigated in randomized clinical trials and demonstrated no significant impact in curvature or plaque size, but reasonable effect on pain control. CONCLUSION: Restorative therapies has emerged as an innovative treatment option for PD and the results from current studies appear to be promising and demonstrated good safety profile. Unfortunately, due to scarce evidence, PRP and SCT are still considered experimental by American Urological Association (AUA) and European Association of Urology (EAU) guidelines. ESWT is recommended, by the same guidelines, for pain control only. More high-quality studies with long-term follow-up outcomes are needed to evaluate efficacy and reproducibility of those therapies.

Role of Gubernaculum testis inervation during the process of testicular migration in human fetuses.

PURPOSE: The gubernaculum seems to be the most important anatomical structure in the testicular migration process. The objective of this paper is to review current literature regarding the role of gubernaculum testis nerves in testicular migration. We conducted a comprehensive literature review about the gubernaculum testis innervation. A PubMed database search was performed in April 2024, focusing on gubernaculum testis and cryptorchidism and genitofemoral nerve (GFN) and calcitonin gene-related peptide (CGRP) gene. The gubernaculum has its own nerve supply, the GFN, descending on the anteromedial surface of the psoas muscle from L1-L2 segments. The second phase of testicular descent is regulated by androgens and CGRP, released from the sensory nucleus of the GFN. The GFN doesn't directly play a role in testicular migration but there is a theory that shows a regulatory function of this nerve in hormonal action during this process. The gubernaculum testis has important structural alterations during the testicular migration and the genitofemoral nerve and CGRP gene are of great importance in this process. The genitofemoral nerve provides motor innervation to the cremaster muscle and gubernaculum, which helps regulate the position of the testes within the scrotum.