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.

Producción científica en investigación sobre avances terapéuticos de la Enfermedad de Peyronie durante los últimos 62 años. Un análisis bibliométrico / Scientific production on research on therapeutic advances in Peyronie's Disease during the last 62 Years. A bibliometric analysis / Produção científica em pesquisa sobre avanços terapêuticos na Doença de Peyronie nos últimos 62 anos. Uma análise bibliométrica

Introducción. La enfermedad de Peyronie es una malformación adquirida del pene, originada por la deposición de placas fibróticas en la túnica albugínea. La prevalencia en Estados Unidos oscila entre el 0.39% y 11.8%, en Europa 8.9%, en Latinoamérica no existe un porcentaje puntual de prevalencia actual debido a la escasez de reportes de esta patología. Este análisis bibliométrico busca describir la evolución terapéutica de la Enfermedad de Peyronie en la literatura de los últimos 62 años, así como la distribución geográfica de estas publicaciones. Metodología. Estudio observacional, descriptivo, un análisis bibliométrico desde 1957 hasta 2019, utilizando GoPubMed y FABUMED. Resultados. Se obtuvieron 721 referencias sobre tratamiento quirúrgico en enfermedad de Peyronie, con un aumento de la producción científica a lo largo del periodo de estudio. The Journal of Urology fue la revista con mayor cantidad de publicaciones, el 57.9% dentro de la categoría de artículo científico. El país líder fue Estados Unidos con 191 publicaciones. Discusión. Existe poca literatura sobre los avances terapéuticos para el tratamiento de enfermedad de Peyronie, lo que dificulta la comparación de las investigaciones a lo largo de los años en diferentes zonas del mundo. La investigación en Latinoamérica es escasa. Conclusión. La investigación sobre el tratamiento quirúrgico en enfermedad de Peyronie muestra un patrón ascendente en la productividad científica durante los años estudiados. Los países con mayores ingresos económicos son de mayor desarrollo en el tema y en menor medida regiones con recursos limitados. El análisis evidencia la importancia de aumentar producción científica en Colombia, así como estimular la investigación sobre este tema, ya que existen muy pocas publicaciones sobre la evolución del tratamiento quirúrgico para esta enfermedad. Palabras clave: Induración Peniana; Enfermedades del Pene; Bibliometría; Fibrosis; Erección Peniana

Introduction. Peyronie's disease is an acquired malformation of the penis, caused by the deposition of fibrotic plaques in the tunica albuginea. The prevalence in the United States ranges between 0.39% and 11.8%, in Europe 8.9%, in Latin America there is no specific percentage of current prevalence due to the scarcity of reports of this pathology. This bibliometric analysis seeks to describe the therapeutic evolution of Peyronie's Disease in the literature over the last 62 years, as well as the geographic distribution of these publications. Methodology. This is an observational, descriptive study, with a bibliometric analysis from 1957 to 2019, using GoPubMed and FABUMED. Results. 721 references on surgical treatment in Peyronie's disease were obtained, with an increase in scientific production throughout the study period. The Journal of Urology was the journal with the highest number of publications, 57.9% within the scientific article category. The leading country was the United States with 191 publications. Discussion. There is a limited amount of literature on therapeutic advances for the treatment of Peyronie's disease, which makes it difficult to compare research over the years in different areas of the world. Research in Latin America is scarce. Conclusion. Research on surgical treatment in Peyronie's disease shows an increasing pattern in scientific productivity over the years. Countries with higher economic income have greater development in the subject and to a lesser extent regions with limited resources. The analysis shows the importance of increasing scientific production in Colombia, as well as stimulating research on this topic, since there are few publications on the evolution of surgical treatment for this disease. Keywords: Penile Induration; Penile Diseases; Bibliometrics; Fibrosis; Penile Erection

Introdução. A doença de Peyronie é uma malformação adquirida do pênis, causada pela deposição de placas fibróticas na túnica albugínea. A prevalência nos Estados Unidos varia entre 0.39% e 11.8%, na Europa 8.9%, na América Latina não existe um percentual específico de prevalência atual devido à escassez de relatos desta patologia. Esta análise bibliométrica tem como objetivo descrever a evolução terapêutica da Doença de Peyronie na literatura dos últimos 62 anos, bem como a distribuição geográfica destas publicações. Metodologia. Estudo observacional, descritivo, análise bibliométrica de 1957 a 2019, utilizando GoPubMed e FABUMED. Resultados. Foram obtidas 721 referências sobre tratamento cirúrgico na doença de Peyronie, com aumento da produção científica ao longo do período do estudo. The Journal of Urology foi o periódico com maior número de publicações, 57.9% dentro da categoria artigo científico. O país líder foram os Estados Unidos com 191 publicações. Discussão. Há pouca literatura sobre avanços terapêuticos para o tratamento da doença de Peyronie, o que dificulta a comparação de pesquisas ao longo dos anos em diferentes partes do mundo. As pesquisas na América Latina são escassas. Conclusão. As pesquisas sobre o tratamento cirúrgico da doença de Peyronie mostram um padrão crescente de produtividade científica ao longo dos anos estudados. Os países com maior rendimento económico são mais desenvolvidos no assunto e, em menor medida, regiões com recursos limitados. A análise mostra a importância de aumentar a produção científica na Colômbia, bem como estimular a pesquisa sobre o tema, uma vez que existem poucas publicações sobre a evolução do tratamento cirúrgico desta doença. Palavras-chave: Induração Peniana; Doenças do Pênis; Bibliometria; Fibrose; Ereção Peniana

Orchio-Septopexy: A new technique to cover and fix detorsed testis undergoing fasciotomy of tunica albuginea

ABSTRACT Purpose Compartment Syndrome (CS) has been recognized as a potential factor that worsens testicular viability after detorsion, especially in borderline cases of prolonged ischemia. Fasciotomy of the testicular tunica albuginea to relieve the pressure associated with CS has been proposed to accommodate edema after detorsion, embracing the raw fasciotomy area with tunica vaginalis flap (TVF) or graft. Fashioning the TVF can be tedious in cases of severe scrotal edema. Herein we present a technique that facilitates and expedites the procedure, maintaining the fasciotomy area decompressed. Materials and Methods In testicular torsion, where the testis remains with dark coloration and questionable viability after detorsion a longitudinal releasing incision is made in the tunica albuginea (fasciotomy) to decrease compartmental pressure. If signs of parenchymal recovery (bleeding points, better color) are seen an orchio-septopexy is performed, suturing the incised albuginea's edges to the septum with a running suture, avoiding CS as well as re-torsion. Results Orchio-septopexy was performed in 11 cases with a mean age of 11.9 years (3-17). All cases had clinic follow-up and testicular Doppler US with a mean of 9.5 months (6-24). 6/11 cases (54%) were salvaged, with good vascularity in the Doppler US and maintained more than 50% testicular volume compared to the contralateral side. Conclusion Orchio-septopexy after testicular fasciotomy is a simple and fast technique that can be utilized in cases of prolonged testicular ischemia and questionable viability. More than half of the testes recovered, encouraging us to propose its utilization as well as its validation by other surgeons.

A Retrospective Study of the Incidence of Subcutaneous Induration Induced by Hydromorphone and Haloperidol

This retrospective study investigated the incidence of subcutaneous induration induced by hydromorphone citrate (HM) and haloperidol (HPD). From September 2018 to December 2019, 75 consecutive patients admitted to our palliative care unit were enrolled. A total of 177 subcutaneous injection sight reactions were assessed from the study initiation to data collection. Patients were then classified into three groups: group A, administered HM + normal saline (NS); group B, administered HM + HPD + NS; and group C, administered HM + HPD + 5% glucose water (Glu). Subcutaneous indurations were observed 29 times at the median of 71.0 (27–151) h. The incidence rates of subcutaneous induration were 4.7% (4/86), 39.1% (18/46), and 15.6% (7/45) in groups A, B, and C, respectively. A significant difference in this rate was observed between groups A and B and between groups B and C. The incidence rates of subcutaneous induration were low in the HM + NS group, but it rose by the addition of haloperidol significantly. Changing from NS to Glu as dilution liquid for HM + HPD decreased subcutaneous induration incidence.

Future considerations in prosthetic urology / 亚洲男科学杂志(英文版)

Since their popularization, genitourinary prosthetics have remained a gold-standard therapy for the treatment of erectile dysfunction and stress urinary incontinence and in cases of testicular loss or dysfunction. They have also represented an area of significant innovation, which has contributed to excellent long-term outcomes. Given this history, the objective of the current review was to provide a 5-10-year outlook on anticipated trends and developments in the field of genitourinary prosthetics. To accomplish this objective, a PubMed and patent search was performed of topics relating to penile and testicular prostheses and urinary sphincters. In regard to penile prostheses, findings demonstrated several new concepts including temperature-sensitive alloys, automated pumps, devices designed specifically for neophalluses, and improved malleable designs. With artificial urinary sphincters, new concepts include the ability to add or remove fluid from an existing system, two-piece systems, and new mechanisms to occlude the urethra. For testicular prosthetics, future implementations may not only better replicate the feel of a biological testicle but also add endocrinological functions. Beyond device innovation, the future of prosthetics is also one of expanding geographic boundaries, which necessitates variable cost modeling and regulatory considerations. Surgical trends are also changing, with a greater emphasis on nonnarcotic, postoperative pain control, outpatient surgeries, and adjunctive techniques to lengthen the penis and address concomitant stress incontinence, among others. Concomitant with device and surgical changes, future considerations also include a greater need for education and training, particularly given the rapid expansion of sexual medicine into developing nations.

Decreased Concentration of Hydromorphone Citrate in Subcutaneous Infusion Therapy Led to the Improvement of Subcutaneous Induration: A Case Report

We reported a clinical case in which decreased concentration of hydromorphone citrate in subcutaneous infusion therapy led to the improvement of subcutaneous induration. A subcutaneous infusion therapy with hydromorphone citrate was initiated in a 60-year-old female pancreatic-cancer patient with back pain. A subcutaneous induration has emerged when the infused concentration of hydromorphone citrate was increased from 0.17% to 0.83%. After the reduction in its concentration (0.28%), that subcutaneous induration has improved. For the alleviation of nausea and sedation, administration of haloperidol and midazolam were added at day 61 and day 70, respectively, with keeping the low concentration (≤0.28%) of hydromorphone citrate. Under this condition, further occurrence of subcutaneous induration was not observed. As a result, we suggested that the concentration of hydromorphone citrate in subcutaneous infusion therapy determined the onset of subcutaneous induration.

Future considerations in prosthetic urology / 亚洲男科学杂志(英文版)

Since their popularization, genitourinary prosthetics have remained a gold-standard therapy for the treatment of erectile dysfunction and stress urinary incontinence and in cases of testicular loss or dysfunction. They have also represented an area of significant innovation, which has contributed to excellent long-term outcomes. Given this history, the objective of the current review was to provide a 5-10-year outlook on anticipated trends and developments in the field of genitourinary prosthetics. To accomplish this objective, a PubMed and patent search was performed of topics relating to penile and testicular prostheses and urinary sphincters. In regard to penile prostheses, findings demonstrated several new concepts including temperature-sensitive alloys, automated pumps, devices designed specifically for neophalluses, and improved malleable designs. With artificial urinary sphincters, new concepts include the ability to add or remove fluid from an existing system, two-piece systems, and new mechanisms to occlude the urethra. For testicular prosthetics, future implementations may not only better replicate the feel of a biological testicle but also add endocrinological functions. Beyond device innovation, the future of prosthetics is also one of expanding geographic boundaries, which necessitates variable cost modeling and regulatory considerations. Surgical trends are also changing, with a greater emphasis on nonnarcotic, postoperative pain control, outpatient surgeries, and adjunctive techniques to lengthen the penis and address concomitant stress incontinence, among others. Concomitant with device and surgical changes, future considerations also include a greater need for education and training, particularly given the rapid expansion of sexual medicine into developing nations.

Subcutaneous Induration Induced by Haloperidol with Hydromorphone Citrate: A Case Report

We report that the discontinuation of haloperidol during subcutaneous infusion therapy with hydromorphone citrate led to the improvement of subcutaneous induration. A 70-year-old female was admitted to our palliative care unit with neck pain. She had neck lymph node metastasis from carcinoma of unknown origin. As subcutaneous infusion of hydromorphone citrate caused nausea, we administered haloperidol with hydromorphone citrate in normal saline. The infusion sites after 4, 9, and 11 days were changed because of subcutaneous induration, which we considered to be caused by haloperidol. After discontinuation of haloperidol, induration at the infusion site was not observed.

How Atypical Penile Curvature Influence Clinical Outcomes in Patients with Peyronie's Disease Receiving Collagenase Clostridium Histolyticum Therapy?

Penile Reconstructive Surgery in Peyronie Disease: Challenges in Restoring Normal Penis Size, Shape, and Function

Evaluation of relaxant responses properties of cinnamon essential oil and its major component, cinnamaldehyde on human and rat corpus cavernosum

ABSTRACT Cinnamomum cassia (Cinnamon) is a well-known traditional medicine with therapeutic benefits for centuries. We evaluated the effects of cinnamon essential oil (CEO) and its main component cinnamaldehyde (CA) on human corpus cavernosum (HCC) and rat CC. The essential oil of cinnamon was analyzed for the confirmation of the oil profile. HCC specimens from patients undergoing penile prosthesis surgery (age 48-69 years) were utilized for functional studies. In addition, erectile responses in anesthetized control and diabetic rats were evaluated in vivo after intracavernosal injection of CEO and CA, and rat CC strips were placed in organ baths. After precontraction with phenylephrine (10µM), relaxant responses to CEO and CA were investigated. CA (96.9%) was found as the major component. The maximum relaxation responses to CEO and CA were 96.4±3.5% and 96.0±5.0% in HCC and 97.5±5.5% and 96.8±4.8% in rat CC, respectively. There was no difference between control and diabetic rats in relaxation responses to CEO and CA. The relaxant responses obtained with essential oil and CA were not attenuated in the presence of nitric oxide synthase (NOS) inhibitor, and soluble guanylate cyclase inhibitor (sGS) in CC. In vivo, erectile responses in diabetic rats were lower than in control rats, which was restored after intracavernosal injection of CEO and CA. CEO and CA improved erectile function and relaxation of isolated strips of rat CC and HCC by a NO/cGMP-independent mechanism. Further investigations are warranted to fully elucidate the restorative effects of CEO and CA on diabetic erectile dysfunction.

Value of ultrasound in diagnosis of Peyronie's disease / 中国医学影像技术

Objective To investigate the value of ultrasound in diagnosis of Peyronie's disease (PD). Methods The ultrasonic characteristics of 48 PD patients were analyzed, and numbers of penile plaques detected with ultrasound and clinical palpation were compared. Results Totally 66 penile plaques were detected with clinical palpation and 80 plaques were detected with ultrasound (Z=1.812 5, P<0.05). Among 80 plaques detected with ultrasound, 48 (48/80, 60.00%) showed medium and high echo, 24 (24/80, 30.00%) showed strong echo, 6 (6/80, 7.50%) were hypoechoic, and 2 plaques (2/80, 2.50%) were hyperechoic accompanied calcification. Strip or punctate blood flow signals were found in the periphery of 4 plaques and the interior of 5 plaques, while strip blood flow signals were detected in the interior and periphery of 1 plaque. Two PD patients accompanied with penile arterial insufficiency, and 1 accompanied with penile veno-occlusive dysfunction. Conclusion Ultrasound is superior to palpation in the detection of penile plaque in PD patients,which can detect blood flow inside and around the plaques and evaluate penile vascular function in patients with erectile dysfunction, providing a basis for clinical treatment and prognostic evaluation of PD.

Effective Switching from High Concentration Morphine Citrate to High Concentration Hydromorphone Citrate for Subcutaneous Induration and Uncontrollable Pain: A Case Report

We report that switching from high concentration morphine citrate to high concentration hydromorphone citrate was effective at reducing the frequency of subcutaneous induration due to subcutaneous infusion and relieving pain. A 66-year-old male was admitted to our palliative care unit with neck pain. He was suffering from neck lymph node metastasis from a carcinoma of unknown origin. We administered a subcutaneous infusion of high concentration morphine citrate (40 mg/ml); however, the infusion site had to be changed about every 3 days because subcutaneous induration occurred and pain-relieving effect of the drug was attenuated. After switching to high concentration hydromorphone citrate (10 mg/ml) diluted to 40%, we no longer needed to change the infusion site due to the drug’s osmolality and the fact that it was a weak irritant and its pH was normalized by its dilution with normal saline. It is worth switching from high concentration morphine citrate to high concentration hydromorphone citrate in terminally ill cancer patients who need subcutaneous infusions of high dose opioids.

The Impact of Clostridium Histolyticum Collagenase on the Prevalence and Management of Peyronie's Disease in the United States

PURPOSE: We evaluated the impact of collagenase clostridium histolyticum (CCH) on rates of diagnosis, treatment, and corporal rupture in Peyronie's disease (PD). We examined the impact of CCH on cost of PD treatment. MATERIALS AND METHODS: We extracted data on PD diagnosis (ICD-9 607.95 and ICD-10 N48.6), corporal rupture (ICD-9 959.13 and ICD-10 S39.840A), CCH use (J0775), penile injections (CPT 54200), and corporal rupture repair from 2008 to 2016 in men over 40 years old using the Clinformatics® Data Mart Database (3.7 to 4.9 million males). We analyzed for prevalence of PD, rates of PD treatments, cost associated with treatment, and rates of corporal rupture and repair by year. RESULTS: The prevalence of PD was 0.29% in 2013 and did not increase after CCH entered the market in 2014. An average of 2.52% of men with PD received treatment before CCH, compared with 3.75% after (p<0.0001). Penile injection rates increased (1.34% vs. 2.61%, p<0.0001), while rates of surgical treatments decreased between these periods. There was no change in rate of corporal rupture in men with PD before (0.024%) and after (0.024%) CCH. Overall, only 20.0% of corporal ruptures were repaired. After CCH entered practice, a significant increase in cost occurred (p=0.013). CONCLUSIONS: The prevalence of men with PD did not change after CCH. However, more men with PD received treatment due to an increase in penile injections. The cost of treating PD increased after CCH became available. The overall prevalence of corporal rupture did not change after CCH entered the market.

Extracorporeal Shock Wave Therapy in Peyronie's Disease: Clinical Efficacy and Safety from a Single-Arm Observational Study

PURPOSE: In this study, we aimed to determine the role of extracorporeal shockwave therapy (ESWT) in the management of Peyronie's disease (PD). MATERIALS AND METHODS: A total of 325 patients suffering from PD were enrolled in this single-arm clinical study. All patients were received ESWT using a schedule of 1 treatment/wk. Penile curvature was measured by a goniometer after intracavernosal drug-induced erection using Alprostadil. Plaque size was measured with a ruler and sexual function assessed by the international index of erectile function (IIEF)-15 score. Severity of erectile dysfunction was classified as severe (IIEF-15 ≤10), moderate (IIEF-15 between 11 and 16), or mild (IIEF-15 between 17 and 25). Results were evaluated at baseline and 3 months after the treatment. RESULTS: All the patients completed the study protocol. Median age was 59.0 years (55.0–64.0 years). After treatment, the median (interquartile range, IQR) plaque size reduced from 1.78 cm2 (1.43–2.17 cm2) to 1.53 cm2 (1.31–1.96 cm2) (p<0.001); the median (IQR) penile length in erection increased from 13.0 cm (12.0–14.0 cm) to 14 cm (13.0–15.0 cm) (p<0.001) and the median (IQR) penile curvature from 30.4° (22.2°–35.4°) to 25.0° (20.2°–30.4°) (p<0.001). We also observed a decrease in pain assessed by visual analogue scale (7 vs. 3; p<0.001), an improvement in each of the IIEF sub-domains (p<0.001) and an improvement in all three PD questionnaire domains (p<0.001). CONCLUSIONS: Based on our findings, ESWT could be considered a safe and efficient minimally invasive option for the management of the patients suffering from PD.

Objective measurements of the penile angulation are significantly different than self-estimated magnitude among patients with penile curvature

ABSTRACT Introduction: The study was aimed to assess the presence of actual differences between the objective and the perceived magnitude of a curvature between patients affected by Peyronie's disease (PD) and congenital penile curvature (CPC). Materials and Methods: Wee analysed a cohort of 88 consecutive patients seeking medi- cal help for either CPC or PD. All patients were invited to provide a self-made drawing of their penis in erection in order to obtain self-provided description of the deformity. An objective measurement of the deformity was also performed drawing two intersecting lines through the center of the distal and proximal straight section of the penile shaft. Results: Our findings showed significant differences between patient self-estimation and the objective measurements of the penile angulation performed by trained experts, with only 32% of patients correctly assessing their own curvature. Overall, patients tended to overestimate (56%) their degree of curvature, but the results are different in patients with PD than those with CPC. In the 60 men (68%) who did not accurately assess their curvature, PD patients generally overestimated their curvature versus CPC patients (67% vs 16%). On the contrary CPC patients underestimated their curvature compared to PD (42% vs. 4%). Conclusion: In order to improve patients' satisfaction rates, the surgeon needs to take into consideration the patient's perception of the deformity when planning the type of surgical correction.

A new technique, combined plication-incision (CPI), for correction of penile curvature

ABSTRACT Introduction Penile curvature (PC) can be surgically corrected by either corporoplasty or plication techniques. These techniques can be complicated by post-operative: penile shortening, recurrent PC, painful/palpable suture knots and erectile dysfunction. Objective To avoid the complications of corporoplasty and plication techniques using a new technique: combined plication-incision (CPI). Materials and Methods Two groups (1&2) were operated upon: group 1 using CPI and group 2 using the 16-dot technique. In CPI, dots were first marked as in 16 dot technique. In each group of 4 dots the superficial layer of tunica albuginea was transversely incised (3-6mm) at the first and last dots. Ethibond 2/0, passed through the interior edge of the first incision plicating the intermediate 2 dots and passed out of the interior edge of the last incision, was tightened and ligated. Vicryle 4/0, passed through the exterior edges of the incisions, was tightened and ligated to cover the ethibond knot. Results Twelve (57.1 %) participants in group 2 complained of a bothering palpable knot compared to none in group 1 with statistically significant difference (P=0.005). Postoperative shortening (5mm) of erect penis, encountered in 9 participants, was doubled in group 2 but with insignificant difference (P>0.05). Post-operative recurrence of PC, was encountered in only 1 (4.8%) participant in group 2, compared to none in group 1, with insignificant difference (P>0.05). Post-operative erectile rigidity was normally maintained in all participants. Conclusion The new technique was superior to the 16-dot technique for correction of PC.

Silencing Histone Deacetylase 7 Alleviates Transforming Growth Factor-β1-Induced Profibrotic Responses in Fibroblasts Derived from Peyronie's Plaque

PURPOSE: Epigenetic modifications, such as histone acetylation/deacetylation and DNA methylation, play a crucial role in the pathogenesis of inflammatory disorders and fibrotic diseases. The aim of this study was to study the differential gene expression of histone deacetylases (HDACs) in fibroblasts isolated from plaque tissue of Peyronie's disease (PD) or normal tunica albuginea (TA) and to examine the anti-fibrotic effect of small interfering RNA (siRNA)-mediated silencing of HDAC7 in fibroblasts derived from human PD plaque. MATERIALS AND METHODS: For differential gene expression study, we performed reverse-transcriptase polymerase chain reaction for HDAC isoforms (1–11) in fibroblasts isolated from PD plaque or normal TA. Fibroblasts isolated from PD plaque were pretreated with HDAC7 siRNA (100 pmol) and then stimulated with transforming growth factor-β1 (TGF-β1, 10 ng/mL). Protein was extracted from treated fibroblasts for Western blotting. We also performed immunocytochemistry to detect the expression of extracellular matrix proteins and to examine the effect of HDAC2 siRNA on the TGF-β1-induced nuclear translocation of Smad2/3 and myofibroblastic differentiation. RESULTS: The mRNA expression of HDAC2, 3, 4, 5, 7, 8, 10, and 11 was higher in fibroblasts isolated from PD plaque than in fibroblasts isolated from normal TA tissue. Knockdown of HDAC7 in PD fibroblasts inhibited TGF-β1-induced nuclear shuttle of Smad2 and Smad3, transdifferentiation of fibroblasts into myofibroblasts, and abrogated TGF-β1-induced production of extracellular matrix protein. CONCLUSIONS: These findings suggest that specific inhibition of HDAC7 with RNA interference may represent a promising epigenetic therapy for PD.

An unanswered question in pediatric urology: the post pubertal persistence of prepubertal congenital penile curvature correction by tunical plication

ABSTRACT Objective: The aim of this study is to analyze post pubertal results of pre pubertal tunica albuginea plication with non-absorbable sutures in the correction of CPC. Materials and Methods: The files of patients who underwent tunica albuginea plication without incision (dorsal/lateral) were retrospectively reviewed. Patients younger than 13 years of age at the time of operation and older than 14 years of age in November 2015 were included. Patients with a penile curvature of less than 30 degrees & more than 45 degrees and penile/urethral anomalies were excluded. All of the patients underwent surgery followed by circumcision. Results: The mean age of patients at the time of the operation was 9.7 years (range, 6-13 years). The mean degree of ventral penile curvature measured during the operation was 39 degrees while it was 41 degrees in the lateral curvatures. All of the patients were curvature-free at the end of the operation. At the time of the follow-up examination, the mean age was 16.7 years (range, 14-25 years). Six patients had a straight (0-10 degrees) penis during erection and seven patients had recurrent penile curvatures ranging from 30 to 50 degrees. Conclusion: Pre pubertal tunica albuginea plication of congenital penile curvature (30-45 degrees) with non-absorbable sutures performed without incision is a minimal invasive method especially when performed during circumcision. However, recurrence might be observed in half of the patients after puberty.

Collagenase Clostridium Histolyticum in the Treatment of Peyronie's Disease: Review of a Minimally Invasive Treatment Option

Peyronie's disease (PD) is an inflammatory disorder characterized by an abnormal collagen deposition in the tunica albuginea of the penis, leading to fibrous and non-compliant plaques that can impede normal erection. Although pharmacological treatments are available, only intralesional injection therapy and surgical reconstruction have demonstrated tangible clinical efficacy in the management of this condition. Intralesional injection of collagenase clostridium histolyticum (CCH) has come to the forefront of minimally invasive treatment of PD. In this review, the authors provide an update on the safety, efficacy, and indications for CCH. The efficacy of CCH will be assessed on the basis of improvement in the severity of penile fibrosis, curvature, and pain. Numerous well-designed clinical trials and post-approval studies involving more than 1,500 patients have consistently demonstrated the efficacy and tolerability of CCH in the treatment of PD. CCH significantly decreases penile curvature and plaque consistency, as well as improves quality of life. Post-approval studies continue to demonstrate the efficacy of CCH despite broader inclusion criteria for treatment, such as the case with acute phase disease and atypical plaque deformities (i.e., ventral plaques, hourglass narrowing). CCH continues to be the gold standard for non-surgical management of stable phase PD, in the absence of strong evidence supporting oral therapy agents and ongoing evaluation of extracorporeal shockwave therapy. However, recent studies are beginning to provide precedent for the use of CCH in the management of acute phase and atypical PD.