Peyronie's Disease Plaque Research Articles

(289) Combined Therapy with Low-intensity Shockwave Therapy and Daily PDE5i Showed Better Pain Relieve and Sexual Function Improvement in Acute Phase of Peyronie Disease

Abstract Introduction To compare the efficacy and safety of daily use PDE5i and PDE5i combined with linear low-intensity shockwave therapy (Li-SWT) in the treatment of acute phase of Peyronie disease (PD). Objective 68 patients with acute PD within 6 month onset were collected. The patients were 26–56 years old with an average of 42.3 years. The patients were randomly divided into two groups, 35 of which were orally administered with 5 mg of tadalafil every night for 3 months; the other 33 received 4 times of Li-SWT with daily PDE5i. Li-SWT uses the Renova shock wave therapy device with an energy density of 0.09mJ/mm2, each time 3200 times in the penile plaque, 900 times in the left and right penile shaft, and once a week for 4 consecutive treatments as a cycle. All patients underwent ultrasound or MRI, penile bending angle measurement, improvement of subjective symptoms, and IIEF-5 scale before and after treatment. Methods 68 patients with acute PD within 6 month onset were collected. The patients were 26–56 years old with an average of 42.3 years. The patients were randomly divided into two groups, 35 of which were orally administered with 5 mg of tadalafil every night for 3 months; the other 33 received 4 times of Li-SWT with daily PDE5i. Li-SWT uses the Renova shock wave therapy device with an energy density of 0.09mJ/mm2, each time 3200 times in the penile plaque, 900 times in the left and right penile shaft, and once a week for 4 consecutive treatments as a cycle. All patients underwent ultrasound or MRI, penile bending angle measurement, improvement of subjective symptoms, and IIEF-5 scale before and after treatment. Results In the PDE5i group, the pain symptom relieve were improved in 80% patients (28 of 35 cases), while the combined group (PDE5i+Li-SWT) were improved in 90.9% patients (30 of 33 cases). The IIEF5 score in the PDE5i group improved from 13.8±7.9 to 19.5±8.1 and from 13.4±7.6 to 21.3±9.2 in the combined group, with both improvement between two groups. The plaque size were shrinkage 5 cases in PDE5i group and 12 cases in combined group, but penile curvature did not change significantly in both groups. In the PDE5i group, 5 patients had mild dizziness and back pain, while 3 patients had mild dizziness and back pain in combined group. There was no obvious adverse reaction observed for Li-SWT treatment. Conclusions Both the daily use PDE5i and the PDE5i combined with Li-SWT can improve the symptoms of acute PD patients, mainly to relieve pain and improve erectile function in some patients. The combined group had a better pain symptom relieve rate and more improvement for sexual function. The two methods can reduce PD plaque size in some cases, while both groups did not significantly change penile curvature. Both methods have good safety in the treatment of acute phase PD. Disclosure No.

Measurement of Oxidative Stress Index (OSI) in Penile Corpora Cavernosa and Peripheral Blood of Peyronie's Disease Patients: A Report of 49 Cases.

Peyronie's disease (PD) is a chronic inflammatory disease affecting the penile albuginea. Oxidative stress (OS) is important for the development of the disease; therefore, it seemed interesting to us to directly measure OS at both the site of the disease and in peripheral blood. For a precise OS study, it is necessary to evaluate not only the single results of the total oxidant status (TOS) and total antioxidant status (TAS) but also their ratio: OS index (OSI) (arbitrary unit) = TOS/TAS × 100. This study included 49 PD patients examined and diagnosed in our Peyronie's care center and a control group of 50 cases. We collected blood samples from both the penis and a vein in the upper extremity; we used d-ROMs and PAT-test (FRAS kit) for OS measurement. Pearson's study found a statistical correlation between penile OSI values and PD plaque volumes: p-value = 0.002. No correlation was found between systemic OSI values and PD plaque volumes: p-value = 0.27. Penile OSI values were significantly reduced after the elimination of the PD plaque (p < 0.00001). The mean value of the penile OSI indices in the PD patients after plaque elimination corresponded to 0.090 ± 0.016 (p = 0.004). The comparison between the penile OSI values of the PD patients (with plaque elimination) and the control group revealed no statistically significant differences (p = 0.130). The absence of a correlation between Peyronie's plaque volume and systemic OSI values indicates that it is preferable to carry out the OS study by taking a sample directly from the site of the disease. By carrying out a penile OSI study, it would be possible to obtain a precise plaque-volume-dependent oxidative marker. Even if the study did not demonstrate any correlation between OSI indices and anxious-depressive state, we detected a high prevalence of anxiety (81.6%) and depression (59.1%) in PD patients.

In vitro efficacy of intralesional Collagenase Clostridium Histolyticum for the treatment of calcified Peyronie's disease plaques.

Peyronie's disease (PD) is defined by penile plaque formation and curvature causing sexual dysfunction. The only FDA-approved intralesional treatment is Collagenase Clostridium histolyticum (CCh). CCh contains two collagenases, AUX1 and AUXII, that break down the type I and type III collagen contained in plaques, leading to plaque dissolution and reduction in penile curvature. Peyronie's plaques, however, also contain fibrin and calcium, which CCh cannot digest. It is unclear if plaque calcification prevents CCh from breaking down plaques. We collected ten tissue samples: five calcified penile plaques and five control samples of corpus cavernosum. They were incubated in CCh or PBS. Soluble collagen measurements and collagen staining assays were completed to measure tissue breakdown. Calcified plaques incubated in CCh showed significantly higher levels of soluble collagen (301.07 ug ± 21.28 vs. PBS: 32.82 ug ± 3.68, p = 0.02), and significantly lower levels of collagen (type I and III) compared to tissues incubated in PBS (0.12 ± 0.08, vs. 0.44 ± 0.17, p = 0.002). When comparing different tissues (calcified vs. control) incubated in CCh and PBS solutions, there were no significant differences in collagen staining or breakdown. Although higher collagen staining was seen in the calcified group, soluble collagen showed no significant differences between control and calcified tissues in the CCh group (control: 0.08 ± 0.02 vs. calcified: 0.17 ± 0.09, p = 0.08) or the PBS group (control: 0.50 ± 0.23 vs. calcified: 0.39 ± 0.39, p = 0.23). CCh exposure led to significantly more tissue breakdown in both tissue groups when compared to PBS however, there was no significant difference in plaque digestion found between calcified and control tissue exposed to CCh or PBS. This suggests that plaque calcification does not affect the action of CCh. Further research into CCh for calcified plaques is necessary to inform clinicians as to the optimal management of this population.

(149) PD.SPHERE, a Novel Three-dimension Cellular Model for Peyronie’s Disease via ‘Microgravity’ Condition: The New Era of in vitro Cell Culture-based Model for PD

Abstract Introduction Peyronie's disease (PD) is a common problem that affects 4-13% of the male population and results in a significant decline in patient and partner quality of life. Currently, in vitro monolayer fibroblast culture and animal models are actively used to study pathogenesis and treatments. However, both models are not a great pathophysiological representative for human PD due to the lack of cellular architecture and limited insight into the PD mechanism. Objective We aimed to develop a three-dimensional (3D) cellular model to reveal the PD pathogenesis mechanism and perhaps use this model as a treatment screening tool. Methods Human PD fibroblasts isolated from PD patients during surgery were cultured in various non-adhesive culture plates under the 'microgravity' condition. Complete media (DMEM+10% FBS+2mM L-glutamine) with and without TGF-β supplement was used to optimize the conditions for the PD.SPHERE, a 3D cell culture model of PD fibroblasts. Molecular probes against nucleus, actin, vimentin (VIM) and smooth muscle actin (SMA) were used to study the morphology and expression of molecular markers. Confocal-microscopic analyses were performed to obtain the morphological snapshots of and molecular data of the PD.SPHERE. Results We successfully developed a 3D cell culture (spheroid) model from human PD fibroblasts with our defined conditions. The PD spheroids were formed individually in each vessel of a 96-well plate coated with a non-adhesive substance. A PD.SPHERE was made in each well in a 96-well plate from three different individuals. Moreover, the size and circularity of spheroids were consistent across the plate. Although TGF-β supplemented condition significantly increased the cell division capability of the PD fibroblasts in the monolayer model, this supplementation was not necessary for our 3D model since TGF-β did not significantly increase the size and circularity of the 3D model. Despite the spheroids' increases in cell density over the culturing period, TGF-β did not affect the cell density in the 3D-cellular structure. Throughout the PD.SPHERE architecture, it also expressed SMA and VIM, the intracellular skeletal markers. Conclusions In conclusion, our model is consistent, reproducible and morphologically relevant to a PD plaque. Our model also demonstrates that we have the potential to produce high throughput treatment screening platforms for PD. Additionally, the PD.SPHERE platform is personalized and customizable to the specific individual; thus, our model indicated the potential to develop this platform for personalized treatment planning. However, signature gene expression and physiological and immunological information (i.e., collagen production, extracellular matrix organization, cellular expression of tight junctions, chemokines, and cytokines) should be further collected to verify the pathophysiological, immunological and treatment response for this model. Disclosure No

An analysis of the mis-diagnosis of Peyronie's Disease (PD) in men referred for the assessment of penile deformity

ABSTRACT Introduction PD is diagnosed in the presence of penile deformity combined with a tunical plaque. Clinical experience shows us that some men who believe they have PD actually have congenital penile curvature (CPC), whilst others, especially those with a history of penile trauma, have anxiety about having PD but, in fact, do not. This analysis aimed to define the mis-diagnosis rate of men referred for PD evaluation. Methods Study population consisted of men who (i) presented to a sexual medicine clinic for the evaluation of penile deformity (ii) and/or the presence of a tunical nodule (iii) underwent comprehensive penile examination by a sexual medicine physician with extensive experience in PD and (iv) underwent penile deformity assessment at the time of penile duplex Doppler ultrasound (PDDU). Demographic and comorbidity data were recorded. Multivariable analysis (MVA) was conducted to define predictors of the absence of PD. Results 1942 patients met the inclusion criteria. 79% were MD referred (MDR), the remainder were self-referred (SR). Mean age of the entire cohort was 58±28 years (MDR 64±22y, SR 41±11y, p&amp;lt;0.01). Comorbidities: hypertension 24%, diabetes 11%, dyslipidemia 27%, chronic pelvic pain syndrome (CPPS) 6%, history of radical pelvic surgery (RPS) 24%, history of penile trauma 8%. Overall 14% of patients had no PD plaque identified on examination (MDR 12%, SR 21%). For MDR without PD, majority had CPC (9%), 3% had no deformity, while for SR only 6% had CPC, the remaining 15% had no deformity at PDDU. Results of MVA is presented in the Table. Conclusion Men referred to a tertiary referral center for the evaluation of PD commonly have no PD. Predictors of no PD include: diagnosis of CPPS, history of penile trauma, young age and absence of RPS. Disclosure Work supported by industry: no.

Plaque excision with the Shah Penile Implant™ and tunica vaginalis graft in Peyronie's disease with erectile dysfunction: A case report.

Peyronie's disease (PD) is a condition characterized by the deposition of scar tissue in the tunica albuginea of the penis. Peyronie's disease often causes pain, worsens the quality of erections, a variable degree of penile deformation and shortening, which can cause severe distress for the patient and the partner and impact negatively on self-esteem and quality of life in general. Surgery still represents the gold standard treatment for PD in the chronic phase, and it aims to guarantee a penis straight and rigid enough to allow the patient to resume penetrative sex with confidence. Penile prosthesis implantation should be reserved for patients with refractory erectile dysfunction or in these patients with complex deformities and impaired erections. Herein is reported the case of a 51-year-old male with a large ossified PD plaque and erectile dysfunction who underwent simultaneous plaque excision and grafting and penile implantation surgery with a semirigid penile prosthesis. This was the first case of penile prosthesis implantation for Peyronie's disease in Indonesia.

Changes in Point of Maximal Curvature During Collagenase Clostridium Histolyticum Injections for Peyronie's Disease

ABSTRACT Introduction Collagenase Clostridium Histolyticum (CCH) is commonly injected at the point of maximal curvature (POMC) for Peyronie's Disease (PD). However, many providers only evaluate the POMC at baseline and do not reassess during CCH injections. As PD plaques often extend over an extended region, it is currently unknown how much the POMC may change throughout a course of CCH treatment. Objective We sought to evaluate for changes in POMC between series among men undergoing CCH injections. Methods A prospective database has been maintained of PD men undergoing CCH injections at two institutions. POMC assessments were obtained prior to each series of injections after pharmacologic erection and were measured from the coronal margin to POMC. An analysis was performed comparing changes in POMC throughout the CCH course, including associated baseline demographic and disease characteristics. Results A total of 445 men (mean age 55.9, mean PD duration 30.6 months) underwent CCH injections from Jan 2014 through Feb 2021. The mean baseline composite curvature was 63.7° (SD 23.7), and the mean distance to curvature was 3.1 cm. Among men who completed 4 series of CCH injections, the mean improvement was 21° (SD 20.6) or 31.7% (SD 33%). In reviewing changes in POMC, the largest change observed at any point within the CCH series was a median 1 cm (IQR 0.5, 2 cm; range 0, 9.5 cm). Compared to baseline, 58% of men experienced a POMC change of 1 cm or greater, 25% 2 cm or greater, and 12% 3 cm or greater during the course of CCH treatment. Age, duration of PD, and baseline curvature were not associated with changes in POMC, although the POMC itself was associated with extent of changes, with proximal curves more likely to experience more notable changes compared to distal ones (p&amp;lt;0.0001). The total improvement in curve was also variably associated with change in POMC, with those experiencing greater improvements noted to have larger change in POMC (p&amp;lt;0.05 for changes in composite curvature and p=0.07 for percent change from baseline). These findings would suggest significant evolution of the POMC during a course of CCH, particularly among men with mid shaft or proximal curves and among those with greater curve improvements. Findings would support a role for repeat curvature assessments prior to each series of CCH injections. Conclusions Based on data from a prospective, two-institution series of PD men undergoing CCH injections, the POMC changes by ≥1 cm in the majority of men. Given the small volume injected with each CCH series, the clinical relevance of these findings and their impact on injector protocols merit further investigation. Disclosure No

EDITORIAL COMMENT

Penile “hourglass” deformity (PHD) is a rare condition that affects about 1% of patients with Peyronie's disease.1 PHD develops from the Peyronie's disease plaque and the tunica albuginea retraction due to the inflammatory process. The final aspect of a penis during tumescence consists of a “clepsydra” shaped shaft and a subsequent psychological and functional impact on the relational life of the patients.2 Erectile dysfunction was reported in 61% – 68% of the patients although it is not clear if this dysfunction could be considered as psychologically or anatomically related.

Mechanical characterization of fibrotic and mineralized tissue in Peyronie's disease.

Peyronie's disease affects penile mechanics, but published research lacks biomechanical characterization of affected tunica albuginea. This work aims to establish mechanical testing methodology and characterize pathological tissue mechanics of Peyronie's disease. Tunica albuginea was obtained from patients (n = 5) undergoing reconstructive surgery for Peyronie's disease, sectioned into test specimens (n = 12), stored frozen at -20 °C, and imaged with micro-computed tomography (µCT). A tensile testing protocol was developed based on similar soft tissues. Correlation of mechanical summary variables (force, displacement, stiffness, work, Young's modulus, ultimate tensile stress, strain at ultimate tensile stress, and toughness) and µCT features were assessed with linear regression. Specimens empirically grouped into hard or soft stress-strain behavior were compared using a Student's t-test. Surface strain and failure patterns were described qualitatively. Specimens displayed high inter- and intra-subject variability. Mineralization volume was not correlated with mechanical parameters. Empirically hard tissue had higher ultimate tensile stress. Failure mechanisms and strain patterns differed between mineralized and non-mineralized specimens. Size, shape, and quantity of mineralization may be more important in determining Peyronie's disease plaque behavior than presence of mineralization alone, and single summary variables like modulus may not fully describe mechanical behavior.

Eficacia y seguridad de la colagenasa de Clostridium histolyticum en la enfermedad de Peyronie según un protocolo de tratamiento modificado

IntroductionCollagenase Clostridium histolyticum (CCH) is the only approved treatment for conservative management of Peyronie's disease (PD) that has demonstrated efficacy and safety in clinical trials. However, as the standard treatment protocol is time and resource consuming, we are introducing a new CCH treatment protocol with a more cost-effective profile. Our goal is to evaluate its efficacy and safety. Materials and methodsWe included patients with PD in stable phase, with curvatures of 30-90degrees. Ventral curvatures and complex deformities were excluded. The treatment protocol consists of a full dose of CCH injected along the PD plaque, forming two lines of four injections. Patients were educated in daily penile modeling activities. The need for a new treatment cycle, up to a maximum of 8 cycles or until the 30-degree curve was decreased, was reevaluated every 4weeks. Changes in curvature and number of cycles were recorded to evaluate the efficacy. Regarding safety evaluation, treatment-related adverse events (TRAEs) were recorded, including rupture of the corpora cavernosa, penile hematoma, hematuria, and local infection. ResultsThirty-one patients were treated under the modified protocol. The mean initial curvature was of 49.84 (±15.83) degrees. Curvature improvement was recorded in 25 patients (80.6%), with a mean absolute reduction of 20.65 (±15.42) degrees and relative reduction of 44%. The mean curvature after treatment was 30.67 (±17.25) degrees. Most patients required one (19.4%) or two (54.8%) injections. No patient presented TRAEs. ConclusionsThe results suggest that the modified CCH treatment protocol is effective and safe, but more studies should be carried out to optimize the current standard protocol.

Vactosertib, a Novel, Orally Bioavailable Activin Receptor-Like Kinase 5 Inhibitor, Promotes Regression of Fibrotic Plaques in a Rat Model of Peyronie's Disease

PurposeTo examine the therapeutic effect of Vactosertib, a small molecule inhibitor of transforming growth factor-β (TGF-β) type I receptor (activin receptor-like kinase-5, ALK5), in an experimental model of Peyronie's disease (PD) and determining anti-fibrotic mechanisms of Vactosertib in primary fibroblasts derived from human PD plaques.Materials and MethodsMale rats were randomly divided into three groups (n=6 per group); control rats without treatment; PD rats receiving vehicle; and PD rats receiving Vactosertib (10 mg/kg). PD-like plaques were induced by administering 100 µL of each of human fibrin and thrombin solutions into the tunica albuginea on days 0 and 5. Vactosertib was given orally five times a week for 2 weeks. On day 30, we performed electrical stimulation of the cavernous nerve to measure erectile function, and the penis was obtained for histological examination. Fibroblasts isolated from human PD plaques were used to determine the anti-fibrotic effects of Vactosertib in vitro.ResultsVactosertib induced significant regression of fibrotic plaques in PD rats in vivo through reduced infiltration of inflammatory cells and reduced expression of phospho-Smad2, which recovered erectile function. Vactosertib also abrogated TGF-β1-induced enhancement of extracellular matrix protein production and hydroxyproline content in PD fibroblasts in vitro by hindering the TGF-β1-induced Smad2/3 phosphorylation and nuclear translocation, and fibroblast-to-myofibroblast transdifferentiation.ConclusionsIn view of the critical role of TGF-β and the Smad pathway in the pathogenesis of PD, inhibition of this pathway with an ALK5 inhibitor may represent a novel, targeted therapy for PD.

Glimpses into the molecular pathogenesis of Peyronie’s disease

Peyronie's disease (PD) is a fibroproliferative disease of the penis. Since little is known about the molecular pathogenesis of PD, we compared the biochemical make-up of PD plaques with normal tunica albuginea to clarify pathological processes in the scarred tissue. Protein and mRNA levels were measured in plaques and in unaffected pieces of the tunica albuginea. We investigated the presence of myofibroblasts, the deposition of collagens, and some key elements of Wnt and YAP1 signaling at protein level. The expression of 45 genes, all related to collagen homeostasis and extracellular matrix proteins, was quantified. In plaques, more myofibroblasts were present, and we observed an activation of Wnt signaling and YAP1 signaling. Increased levels of the collagens types I and III confirm the fibrotic nature of plaques. The mRNA ratio of collagen types III, IV, and VI to type I was increased. The expression of lysyl hydroxylase 3 was higher, whereas a decreased expression level was seen for fibronectin and cathepsin K. The biochemical composition of plaques was different from unaffected tunica albuginea: the relative and absolute abundance of various extracellular matrix proteins were changed, as well as the quality of collagen and the level of the collagen-degrading enzyme cathepsin K.

Sixty years in the making: collagenase Clostridium histolyticum, from benchtop to FDA approval and beyond.

The introduction of collagenase Clostridium histolyticum (CCH) as the first and only FDA-approved non-surgical treatment for Peyronie's disease (PD) has been an important step in its management. Our aim is to provide an overview of the historical origins of CCH and its development through FDA approval and beyond for the treatment of PD. A PubMed search using the terms Peyronie OR Peyronie's AND collagenase and limited to clinical research studies resulted in 24 articles that were examined for the current review. PD is a connective tissue disorder of the penile tunica albuginea involving fibrotic penile plaques that cause abnormal curvature and, in many cases, erectile pain. Although the exact mechanism and underlying pathophysiology are not well characterized, the known lability of these plaques to exogenous bacterial collagenase combined with a lack of effective medical therapies led to the development of CCH as an evidence-based treatment of PD. The initial discovery of collagenase was followed by in vitro studies on PD plaque tissue and following the phase 3 IMPRESS trial culminated in FDA approval of CCH in 2013. Future directions in CCH therapy include improved patient selection, use in acute phase PD, adjuvant and combination therapies, and novel delivery mechanisms. CCH provides an effective non-surgical treatment option for men with PD. We have traced the development of CCH in the treatment of PD from the earliest in vitro investigations to comprehensive multi-study meta-analyses confirming its highly rated efficacy when compared to other historical non-surgical remedies.

PS-04-004 Transcriptome-wide analysis of Peyronie's disease plaques using RNA sequencing uncovers targetable signaling pathways for medical therapy

[Milenkovic, U.] Katholieke Univ Leuven, Dept Dev & Regenerat, Leuven, Belgium. [Janky, R.; De Ridder, D.; Albersen, M.] Katholieke Univ Leuven, Leuven, Belgium. [Hatzichristodoulou, G.] Julius Maximilians Univ, Wurzburg, Germany. [van Renterghem, K.] Univ Hasselt, Hasselt, Belgium. [Cellek, S.] Anglia Ruskin Univ, Chelmsford, Essex, England. [Bivalacqua, T.] Johns Hopkins Univ, Baltimore, MD USA.

Inflatable Penile Prosthesis Placement, Scratch Technique and Postoperative Vacuum Therapy as a Combined Approach to Definitive Treatment of Peyronie’s Disease

Peyronie's disease is a devastating condition resulting in penile malformation, erectile dysfunction, pain and emotional distress. In this prospective, 2 institution study we evaluated a multimodal surgical and mechanical combined approach to the definitive treatment of Peyronie's disease and concomitant erectile dysfunction. A total of 145 select patients underwent endocavernous disruption of Peyronie's disease plaques via the scratch technique, followed by inflatable penile prosthesis insertion. Postoperatively patients were assigned to vacuum device therapy for 3 minutes twice daily to continue penile curvature correction. Followup continued for 1 year after surgery. Anatomical and functional results were assessed. Patients with plaques in the proximal third, middle third and subcoronal areas of the penis had a mean ± SD postoperative residual curvature of 21.5 ± 4.5, 17.3 ± 4.8 and 14.1 ± 3.1 degrees, respectively. After 24 weeks of vacuum therapy the mean penile curvature deviation decreased to 8.7 ± 2.5, 9.1± 2.9 and 7.7 ± 0.9 degrees, respectively. The mean IIEF-5 (International Index of Erectile Function) score was 9.8 ± 2.3 preoperatively, 18.9 ± 3.1 at 6 months (p <0.001) and 24.1 ± 3.6 at 1 year (p <0.001). The mean EDITS (Erectile Dysfunction Inventory of Treatment Satisfaction) score at the end of followup was 64.6 ± 11.8. Operative and postoperative complications were minimal. Our novel combination of intraoperative and postoperative therapies in the treatment of patients with Peyronie's disease and an inflatable penile prosthesis was safe and efficacious with excellent functional outcomes. Penile curvature corrections were statistically significant and complications were negligible.

330 Residual Curvature after Penile Prosthesis: The Role of Peyronie's Patch Grafts

Peyronie's disease (PD) and erectile dysfunction (ED) can both be treated by placement of a penile prosthesis (PP). After PP placement, persistent penile curvature may be addressed with maneuvers such as penile modeling or PD plaque incision/excision with or without patch grafts. Outcomes data regarding the use of patch grafts during the same operation as penile prostheses is sparse. The purpose of this study is to analyze and present our institution's experience using patch grafts to correct residual penile curvature after PP placement. The study aims to verify that these procedures can be safely and efficiently conducted at the same operation. After IRB approval, all patients who underwent PP surgery from October 2011 through April 2017 at our university were identified. All surgeries that concurrently involved a patch graft procedure to correct residual PD curvature at the time of IPP were then isolated. The pre- and post-operative demographics, as well as intra-operative findings, were collected for each patient.

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

PurposeEpigenetic 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 MethodsFor 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.ResultsThe 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.ConclusionsThese findings suggest that specific inhibition of HDAC7 with RNA interference may represent a promising epigenetic therapy for PD.

Review of Management Options for Patients With Atypical Peyronie's Disease.

Peyronie's disease (PD) is a wound-healing disorder of the tunica albuginea often associated with penile deformity. Less commonly, patients with PD might display atypical presentations such as ventral curvature, hourglass deformity, significantly shortened penis, and/or multiplanar curvature. To review the available literature on the prevalence of and management options for atypical PD. A literature review was performed through PubMed from 1982 through 2016 regarding atypical PD. Keywords used for the search were Peyronie's disease, atypical Peyronie's disease, ventral Peyronie's disease, ventral plaque, hourglass deformity, penile indentation, penile notching, short penis, shortened penis, shrunken penis, biplanar curvature, and multiplanar curvature. To assess the various surgical and non-surgical techniques used for the management of atypical PD. Collagenase Clostridium histolyticum is contraindicated for patients with ventral plaques and/or hourglass deformities. Patients with maintained erectile function and ventral PD plaques are best treated with intralesional injections of interferon alpha-2b or tunica plication. Patients with maintained erectile function with PD associated with hourglass deformity and/or multiplanar curvature are best treated with plaque incision or partial excision and grafting. Patients with a shortened penis could attempt conservative measures such as penile traction therapy and medical management. When erectile function is compromised, insertion of an inflatable penile prosthesis with or without ancillary straightening procedures should be recommended. Lengthening procedures can be attempted in very special circumstances by expert surgeons. There is a paucity of data regarding atypical PD. Ventral plaques can be treated with intralesional injections or surgery, hourglass deformity and multiplanar curvatures are best managed surgically, and a shortened penis should be treated with non-invasive approaches. When concomitant erectile dysfunction is present, insertion of an inflatable penile prosthesis is recommended. Caution should be advised before undergoing ancillary penile lengthening maneuvers owing to the potential for serious complications. Yafi FA, Hatzichristodoulou G, DeLay KJ, Hellstrom WJG. Review of Management Options for Patients With Atypical Peyronie's Disease. Sex Med Rev 2017;5:211-221.

Bone Saw for Calcified Peyronie's Disease Plaques

To determine the incidence of calcified Peyronie's disease plaque that cannot be cut with a blade in a 100-case series and to describe the use of a soft tissue-protecting bone saw for plaque incision. Chart reviews were done of all surgically treated Peyronie's disease patients at our center between October 1996 and December 2012. 100 cases were included. We evaluated our novel technique of tissue-protecting bone saw surgical use. 100 consecutive patients underwent surgery for Peyronie's disease, and 6 required transverse bone saw plaque incision due to the severity of calcification that could not be cut with a blade. Four of those 6 underwent grafting procedures with porcine submucosal intestinal substance (SIS) and 2 underwent placement of inflatable penile prosthesis (IPP) after plaque incision. There were no surgical complications. Both IPP patients had functioning prosthesis 4 and 7.3 years after surgery. One SIS-graft patient required re-operation for more proximal curvature 11 months later and ultimately required multiple plaque incisions and an IPP. Densely calcified plaques occurred in 6% of a surgical series of Peyronie's disease patients. The vibrating bone saw is a novel technique to incise calcified plaques before grafting or IPP placement.

Collagenase Clostridium histolyticum for the Treatment of Peyronie's Disease: The Development of This Novel Pharmacologic Approach.

The conception of collagenase Clostridium histolyticum (CCH) as treatment for Peyronie's disease (PD) was a vital first step in providing a nonsurgical, minimally invasive FDA-approved treatment for men with PD. To review the origins, clinical research history, and ultimately FDA approval of collagenase as PD treatment. A PubMed search using (Peyronie's or Peyronie) AND collagenase, and limited to clinical research studies, returned nine papers that were examined in the current review. Collagenase as a PD treatment arose in response to a lack of effective nonsurgical treatments and the incomplete understanding of underlying PD etiology. Awareness of dense collagen in PD scarring and parallel initial exploration of collagenase to treat herniated lumbar discs coincided with and inspired laboratory-based investigation of collagenase effects on excised PD plaque tissue. The foundational conceptual work and the critical development of purified injectable collagenase allowed the pursuit of clinical studies. Progression of clinical studies into large-scale robust trials culminated in two important outcomes: development of the first validated, PD-specific measure of psychosexual function, the Peyronie's Disease Questionnaire, and the first FDA-approved treatment for PD. Collagenase therapy began as an attempt to modify the structure of PD-related tunica albuginea scarring, despite the lack of a fundamental understanding of the scar's origin. If we wish to advance PD treatment beyond this first effective step, the future needs to bring us full circle to the starting point: We need a greater understanding of the control of collagen deposition and wound healing in men with PD.