Peyronie's Disease Research Articles

Injectable agents for the induction of Peyronie's disease in model rats: a comparative study.

Peyronie's disease (PD) is a disorder characterized by fibrous plaque formation in the penile tissue that leads to curvature and complications in advanced stages. In this study, we aimed to compare four injectable induction agents for the establishment of a robust rat model of PD: transforming growth factor-β1 (TGF-β1), fibrin, sodium tetradecyl sulfate (STS) combined with TGF-β1, and polidocanol (POL) combined with TGF-β1. The results showed that injection of TGF-β1 or fibrin into the tunica albuginea induced pathological endpoints without causing penile curvature. The STS + TGF-β1 combination resulted in both histological and morphological alterations, but with a high incidence of localized necrosis that led to animal death. The POL + TGF-β1 combination produced pathological changes and curvature comparable to STS + TGF-β1 and led to fewer complications. In conclusion, fibrin, STS + TGF-β1, and POL + TGF-β1 all induced PD with a certain degree of penile curvature and histological fibrosis in rats. The POL + TGF-β1 combination offered comparatively greater safety and clinical relevance and may have the greatest potential for PD research using model rats.

Imaging techniques for diagnosing and managing Peyronie disease.

Erectile dysfunction (ED) affects up to 50% of men to some degree and has a variety of physiologic and psychologic causes, but many patients do not seek specialist treatment. One cause of ED is Peyronie disease (PD) defined by the presence of fibrotic plaques in the tunica albuginea which cause painful penile contractures. While diagnosing PD relies on clinical history and a focused history and physical exam, adding imaging studies can identify nonpalpable plaques and any underlying vasculogenic ED to tailor the extent of surgical treatment and determine when implantable penile prostheses are beneficial. After briefly reviewing penile anatomy, erectile function, and the clinical features of PD, this paper describes the imaging findings of vasculogenic ED on Doppler ultrasound (US), followed by the imaging appearance of PD on US, computed tomography (CT), and magnetic resonance imaging (MRI) to increase recognition of this disease and show how imaging can be used as a problem-solving tool for treatment planning and evaluating post-surgical complications, especially malfunctioning implanted devices. By increasing the understanding of how imaging can be used for patients with PD with or without vasculogenic ED before and after treatment, radiologists and urologists can collaborate on patient management.

Prompt matters: evaluation of large language model chatbot responses related to Peyronie's disease.

Despite direct access to clinicians through the electronic health record, patients are increasingly turning to the internet for information related to their health, especially with sensitive urologic conditions such as Peyronie's disease (PD). Large language model (LLM) chatbots are a form of artificial intelligence that rely on user prompts to mimic conversation, and they have shown remarkable capabilities. The conversational nature of these chatbots has the potential to answer patient questions related to PD; however, the accuracy, comprehensiveness, and readability of these LLMs related to PD remain unknown. To assess the quality and readability of information generated from 4 LLMs with searches related to PD; to see if users could improve responses; and to assess the accuracy, completeness, and readability of responses to artificial preoperative patient questions sent through the electronic health record prior to undergoing PD surgery. The National Institutes of Health's frequently asked questions related to PD were entered into 4 LLMs, unprompted and prompted. The responses were evaluated for overall quality by the previously validated DISCERN questionnaire. Accuracy and completeness of LLM responses to 11 presurgical patient messages were evaluated with previously accepted Likert scales. All evaluations were performed by 3 independent reviewers in October 2023, and all reviews were repeated in April 2024. Descriptive statistics and analysis were performed. Without prompting, the quality of information was moderate across all LLMs but improved to high quality with prompting. LLMs were accurate and complete, with an average score of 5.5 of 6.0 (SD, 0.8) and 2.8 of 3.0 (SD, 0.4), respectively. The average Flesch-Kincaid reading level was grade 12.9 (SD, 2.1). Chatbots were unable to communicate at a grade 8 reading level when prompted, and their citations were appropriate only 42.5% of the time. LLMs may become a valuable tool for patient education for PD, but they currently rely on clinical context and appropriate prompting by humans to be useful. Unfortunately, their prerequisite reading level remains higher than that of the average patient, and their citations cannot be trusted. However, given their increasing uptake and accessibility, patients and physicians should be educated on how to interact with these LLMs to elicit the most appropriate responses. In the future, LLMs may reduce burnout by helping physicians respond to patient messages.

Acute Phase Peyronie's Disease: Where Do We Stand?

Peyronie's disease (PD) is a common benign condition characterized by superficial fibrosis and scar formation at the tunica albuginea of the penis, eventually leading to penile curvature. It is believed that penile micro-traumas during intercourse and subsequent activation of inflammatory processes constitute the pathogenetic basis of the disease. Routinely, PD is divided into acute and chronic phases, with pain during erection or flaccid state being the hallmark of the former. Surgical intervention should be avoided during the acute phase, as the risk of recurrence or progression of penile deformity during this stage might affect the optimal outcomes of the procedure. During this stage, many conservative treatment options have been suggested, including oral, topical, and intralesional therapies, extracorporeal shock wave therapy (ESWT), and penile traction therapy (PTT). Currently, the optimal treatment consists of a combined treatment strategy with phosphodiesterase type 5 inhibitors (PDE5Is), ESWT for pain management, PTT, and intralesional therapies. Large, well-designed randomized controlled trials (RCTs) are necessary to further elucidate the most efficient treatment option for acute phase PD.

Nonsurgical treatment of Peyronie's disease

Nonsurgical treatment of Peyronie's disease

MR imaging of penile pathology and prostheses.

Penile MRI is a vital yet underutilized diagnostic tool that provides detailed information crucial for managing various penile pathologies. Due to its infrequent use, many radiology trainees lack confidence in interpreting these exams. This article reviews the anatomy, key technical considerations, and interpretive pearls for penile trauma, Peyronie's disease, priapism, penile neoplasms, prosthesis evaluation, and a few miscellaneous conditions. Through illustrative case examples, this review aims to enhance the understanding and proficiency of radiologists in performing and interpreting penile MRI in these clinical scenarios.

Comment on: "Use of thermographic imaging for the evaluation of erectile dysfunction and Peyronie's disease".

Comment on: "Use of thermographic imaging for the evaluation of erectile dysfunction and Peyronie's disease".

Long-term penile prosthesis couple's satisfaction: A systematic review and meta-analysis.

Data supporting successful and satisfactory penile prosthesis (PP) implantation outcomes are mainly based on subjective, rather than objective, analysis. To systematically review and objectively analyze, all available data related to patient and partner PP satisfaction. An extensive search was performed, including the following key-words: ("penile prosthesis" and "satisfaction"). The search, which accrued data from January 1, 1969, up to July 31, 2023, was restricted to English-language articles including human participants. Out of 663 retrieved articles, 83 were considered including, 12,132 subjects with a mean age and mean follow-up of 58.6 [range 20; 77.1] years and 47.6 [range 6; 374] months, respectively. Overall, a high patient satisfaction rate was observed 83[80; 86]%. The satisfaction rate increased in subjects with three-piece PP and in those with a higher rate of cardiovascular or neurological diseases and was independent of the patient's age. Partner's satisfaction rate was lower when compared to that observed in men and it increased according to the use of inflatable devices and the presence of patient Peyronie's disease. The long-term complication rate was limited ranging from 3% for erosion to 4.6% when mechanical failure was considered. Patient and partner satisfaction is excellent and increases with time. The number of complications is limited and is strongly associated with the presence of diabetes mellitus. We found a high couple satisfaction score that was higher when reported by males compared to females. Patient satisfaction increased with time, and it was independent of age.

An overview of the Canadian landscape on the use of restorative therapies for erectile dysfunction and Peyronie’s disease

Introduction: Restorative therapies (RT(s)), including low-intensity shockwave therapy (Li-SWT) and platelet-rich plasma (PRP), aim to restore natural erectile function. Many clinics offer these therapies for erectile dysfunction (ED) and Peyronie’s disease (PD) with direct-to-consumer (DTC) marketing. This study sought to investigate the landscape of RTs within Canadian clinics. Methods: Online searches were made to identify clinics offering Li-SWT and/or PRP as an RT for treating ED and PD in Canada. Public websites were analyzed, followed by calling clinics for data on cost, treatment protocols, clinic ownership, success rates, and adjunctive therapies. Results: A total of 107 clinics were identified online, with a 68.2% call response rate (n=73). Of the respondents, 56 and 40 clinics provided Li-SWT and PRP therapies, respectively, with 23 clinics offering both. All clinics reported using RTs for ED, with 21 clinics offering Li-SWT and 22 clinics providing PRP for PD. Forty-three clinics provided costs and protocols for Li-SWT, while 33 clinics did so for PRP. The average cost + standard deviation (CAD) of six sessions of Li-SWT was $2167.24+936.11 and one shot of PRP was $1478.68+591.98. Most (60.3%, n=44) clinics reported physician ownership, with a majority (n=28) being family medicine trained. Seven clinics did not provide data and 22 were non-MD-owned. Ten clinics provided success rates, with an average of 87.3%. Conclusions: Despite limited data supporting their routine clinical use, many clinics across Canada offer RTs for ED and PD with varying treatment protocols and increased costs. Further research is required to evaluate the efficacy of RT for ED and PD.

Use of thermographic imaging for the evaluation of erectile dysfunction and Peyronie's disease.

Thermographic imaging is a technique to measure infrared radiation to report temperature and has been used in prior research to assess sexual arousal by measuring genital temperature. We hypothesized this can be used quantitatively to assess erectile function. We conducted an observational clinical trial of this technique by performing thermographic imaging in the flaccid and erect state and compared these values with hemodynamic measurements performed by penile Doppler/duplex ultrasound (PDDU). We also hypothesized that in men with Peyronie's disease (PD), the plaque would be visible on thermographic imaging and took thermographic measurements in this area for patients with PD. Any man scheduled to undergo PDDU in our urology clinic was approached for recruitment. PDDU was performed by one of two experienced urologists. We recruited 30 men for this study. Seven of these men had PD. The change in measured temperature between flaccid and erect states correlated significantly with the peak systolic velocity r = 0.46 (p = 0.025). In the seven men with PD the mean change in temperature of the plaque was +0.9 °C versus +2.1 °C in the normal penis (p = 0.28). Thermographic imaging shows a significant correlation with objective hemodynamic measurements on PDDU.

Early-onset and uncontrolled diabetes mellitus factors correlate with complications of Peyronie's disease.

Peyronie's disease (PD) is a connective tissue disorder that affects the penis and is characterized by abnormal collagen structure in the penile tunica albuginea, resulting in plaque formation and penile deformity. PD's overall prevalence is estimated at 3.2% to 8.9%, with rates as high as 20.3% among men with type 2 diabetes mellitus (DM). However, the characteristics of DM associated with PD complications remain unclear. To explore clinical associations between DM characteristics and PD complications. We conducted a retrospective analysis of patients with DM and PD who presented at our institution between 2007 and 2022. We examined patients' clinical histories, DM- and PD-related clinical parameters, and complications. Penile deformities were assessed through physical examination, photographs, and penile Doppler ultrasound. Patients were categorized into subgroups based on age of DM onset: early (<45years), average (45-65years), and late (>65years). Outcomes included effects of DM characteristics on PD development, progression, and severity. In total, 197 patients were included in the evaluation. Early-onset diabetes and elevated hemoglobin A1c (HbA1c) levels exhibited significant correlations with the early development of PD (ρ = 0.66, P < .001, and ρ = -0.24, P < .001, respectively). Furthermore, having DM at an early age was associated with the occurrence of penile plaque (ρ = -0.18, P = .03), and there were no significant differences in plaque dimensions (ρ = -0.29, P = .053). A rise in HbA1c levels after the initial PD diagnosis displayed positive correlations with the formation of penile plaque (ρ = 0.22, P < .006). These findings emphasize the need for comprehensive assessments and personalized treatment strategies for individuals with DM and PD. Enhanced management approaches can improve outcomes for those facing both challenges. Limitations include the single-site retrospective design with potential selection bias, inaccuracies in medical record data, and challenges in controlling confounding variables. This study highlights that early-onset diabetes and poor diabetes control, as indicated by a subsequent rise in HbA1c levels following PD diagnosis, are significantly correlated with the onset and severity of PD. Revealing the mechanisms behind these findings will help us develop better management strategies for individuals with DM and PD.

Peyronie's disease - a condition affecting many

Peyronie's disease - a condition affecting many

Kindlin-2 mediates Peyronie's disease through activation of TGF-β/Smad signaling pathway under the presence of TGF-β1

BackgroundPeyronie's disease (PD) causes benign plaques or induration in tunica albuginea (TA). Kindlin-2 regulates the TGF-β1/Smad3 pathway, which accelerates kidney fibrosis. The study is aimed mainly to investigate the impact of Kindlin-2 on PD formation and its signaling pathways, notably the TGF-β/Smad pathway in the presence of TGF-β1. MethodsIn this mouse investigation, adenovirus TGF-β1 was injected into TA to produce PD. The model was successfully induced 45 days later. Western Blot (WB) and immunohistochemistry (IHC) were utilized to measure Kindlin-2 in PD model tissue. WB and immunofluorescence assays were utilized to confirm the impact of TGF-β1 on Kindlin-2 levels in vitro. The interaction among Kindlin-2, TβRI, and Smad3 was detected using immunoprecipitation (IP) experiments. We examined how TGF-β1 affects Smad3 phosphorylation and downstream gene activation process. Finally, Kindlin-2 and the level of tissue fibrosis were examined in PD model. ResultsKindlin-2 levels were elevated in the TGF-β1-induced PD model, confirming that TGF-β1 can increase Kindlin-2 levels in primary PD cells. Moreover, Kindlin-2 mediates Smad3-TβRI interaction, activates p-Smad3, and enhances TGF-β1 target gene expression. In vivo investigations reveal that Kindlin-2 promotes PD development and tissue fibrosis. The regulatory effects of Kindlin-2 need the presence of TGF-β1. Tissue fibrosis can be reduced by downregulating Kindlin-2. ConclusionKindlin-2 does not directly activate Smad3 to induce tissue fibrosis. Instead, it exerts its effect through the combined influence of TGF-β1. Inhibiting Kindlin-2 could potentially be a treatment for PD.

Commentary on: Use of Himplant® for correction of residual deformity following prior treatment of Peyronie's disease: a case report.

Commentary on: Use of Himplant® for correction of residual deformity following prior treatment of Peyronie's disease: a case report.

Role of lingual mucosa as a graft material in the surgical treatment of Peyronie's disease.

Peyronie's disease (PD) is a localized fibrosis of tunica albuginea, which causes the anatomical and functional changes to the penis. Corporoplasty with grafting is indicated in severe (>60°) and complex curvature. Buccal mucosa is the most favored autologous graft material nowadays. The ventrolateral aspect of lingual mucosa has similar histological features to the rest of the oral cavity. This study aimed to test the efficacy, safety, durability, and reproducibility of corporoplasty with lingual mucosal graft (LMG) in the surgical treatment of PD in terms of surgical outcome, sexual function, and donor site complications. This prospective study included 19 patients of PD with severe and complex curvature, who underwent corporoplasty with LMG. Surgical and functional outcomes were assessed at follow-up planned at 2 weeks, 3 months, 6 months, 1 year, and 2 years. The mean operative time was 126.31 ± 21.45 min. Additional Nesbit's plication to correct the residual deformity was required in 26% (5 / 19) of patients. Straightening of the penis (curvature <10°) was achieved in 89% (17 / 19) of patients. Increase in the penile length (>1 cm) postoperatively was achieved in 63% (12 / 19) of patients and a shortening of penis occurred in 5% (1 / 19) of patients. Newer onset erectile dysfunction developed in 11% (2 / 19) of patients, and patient and partner satisfaction rates were 89% (17 / 19) and 84% (16 / 19), respectively, in a mean follow-up of 20.66 ± 5.37 months. Donor site complications were minimal and no patient had any salivary changes or speech disturbances. LMG provided excellent short-term results in terms of deformity correction, improved sexual function, and minimal donor site morbidity. The method is simple and reproducible, and multicenter studies with larger number of cases with longer follow-up are required to confirm these favorable results.

Prospective Pilot Study: Tolerability of Outpatient Penile Plication Under Nursing-Administered Conscious Sedation vs Anesthesiologist-Administered Deep Sedation.

Penile plication is commonly performed for Peyronie's disease under general or spinal anesthesia. Conscious sedation (CS) offers decreased anesthetic risks, cost-effectiveness, and the ability to perform the procedure in outpatient settings with shorter wait times. We sought to compare tolerability of penile plication under deep intravenous sedation (DIS) administered by anesthesiologists and nursing-administered CS (NACS). Tolerability for penile plication was prospectively evaluated, excluding revision surgeries and those with hourglass or hinge deformities. DIS included midazolam and ketamine with infusion of propofol and remifentanil. NACS consisted of midazolam and fentanyl. Baseline characteristics, procedural information, and patient- and surgeon-reported pain assessments were collected. Patients were administered a standardized tolerability questionnaire on follow-up. Forty patients were enrolled (23 DIS; 17 NACS) with similar baseline characteristics. Median curvature of the DIS cohort was 55° (interquartile range = 43.75-76.25) and 45° (interquartile range = 45-60) in NACS. There was a 100% success rate with no procedure abortion or conversion to general anesthetic. On follow-up, all patients had functional curvature (<20°), and 100% of patients in the DIS and NACS cohorts reported that they would recommend CS to others. Over 93% of patients in both cohorts would choose CS over general anesthetic in the future, with no differences in perioperative and postoperative pain between groups. Penile plication with CS, whether administered by an anesthesiologist or nursing, is well tolerated with no differences in pain or complications. This indicates that outpatient penile plication with trained nursing staff administering CS can safely reduce costs, risks, and wait times.

MicroRNA-29b attenuates fibrosis in a rat model of Peyronie's disease.

Peyronie's disease is characterized by the formation of fibrotic plaques in the penile tunica albuginea. Effective treatments are limited, warranting the investigation of new promising therapies, such as the application of microRNAs that regulate fibrosis-related genes. We aimed to investigate the therapeutic potential of mimicking microRNA-29b in a fibrin-induced rat model of Peyronie's disease. The study was designed in two phases. To establish an optimal Peyronie's disease model, rats received either human fibrin and thrombin or saline solutions into the tunica albuginea on days 0 and 5. The animal model validation was done through expression and histopathological analyses, the latest by an experienced uropathologist. After validation, we performed microRNA-29b treatment on days 14, 21, and 28 of the study. This phase had control (normal saline) and scramble (microRNA scramble) groups. The mid-penile shaft was removed on day 30 for histological examination and molecular analyses in both study stages. The control group displayed typical tunica albuginea histologic architecture in the animal model validation. In Peyronie's disease group, the Hematoxylin and eosin and Masson Trichrome staining methods demonstrated an interstitial inflammatory process with concomitant dense fibrotic plaques as well as disarrangement of collagen fibers. Additionally, we found out that reduced microRNA-29b (p=0.05) was associated with significantly increased COL1A1 and transforming growth factor β1 genes and proteins (p>0.05) in the Peyronie's disease group. After treatment with mimic microRNA-29b stimulation, the Hematoxylin & eosin and Masson Trichrome staining revealed a discrete and less dense fibrotic plaque. This result was associated with significantly decreasing expression of COL1A1, COL3A1, and transforming growth factor β1 genes and proteins (p<0.05). The fibrin-induced animal model showed significant histopathological and molecular changes compared to the Control group, suggesting that our model was appropriate. Previous findings have shown that increased expression of microRNA-29b was associated with decreased pathological fibrosis. In the present study, treatment with microRNA-29b decreased the gene and protein expression of collagens and transforming growth factor β1. This study reveals the therapeutic potential for Peyronie's disease involving molecular targets. MicroRNA-29b application on the rat's tunica albuginea attenuated fibrosis, arising as a novel potential strategy for Peyronie's disease management.

Penile prosthesis implantation is safe and effective in Peyronie's disease patients with and without erectile dysfunction.

Penile prosthesis (PP) is the mainstay of treatment in Peyronie's disease (PD) with co-existent refractory erectile dysfunction (ED). This study aimed to assess the clinical outcomes of patients who underwent PP as the first-line surgical treatment in PD without ED. A total of 636 patients underwent PP for PD from 2012 to 2022, but only 168 patients who underwent PP as first-line surgical management for PD with or without ED were included in the study. The mean (SD) age of 168 patients was 56.3 years (12.4). The mean curvature of the "PD with ED" group and the "PD without ED" group were 38.2 (5.6) degrees and 42.2 (5.9) degrees. The median (IQR) follow-up was 56.0 months (34.5- 61.4). Most (86.9%) patients underwent 3-piece inflatable PP. An important finding is that 33 patients (19.6%) without ED had undergone PP. Mechanical failure requiring revision surgery was less common in the 'without ED' group than in the ED group (6.8% vs. 10.2%, p 0.04). Most PD patients without ED (87.9%, 29/33) and with ED (88.9%, 120/135) were "satisfied" after PP implantation at six months, as defined by a score of ≥4 on a 5-point Likert scale. If surgery is offered in PD, PP may be considered a safe and effective first-line surgical treatment regardless of the ED, given the acceptable complications and high satisfaction rates. However, this new concept warrants further research.

Multimodal treatments based on Tadalafil during acute phase of Peyronie's disease: experience at two referral academic centers.

The purpose of this study is to identify the clinical outcomes of patients during acute phase of Peyronie's disease (PD) treated with daily Tadalafil 5mg associated with non-surgical treatments such as intra-plaque verapamil injections (IVI), vacuum erection devices (VED) or extra corporeal shockwave therapy (ESWT). 445 patients with PD in acute stage were treated as it follows: Group 1(G1) 117 men with only Tadalafil 5mg once a day for 3months; Group 2(G2) 106 men with IVI plus Tadalafil 5mg for a period of 12weeks; Group 3(G3) 124 men that received ESWT for 6weeks plus Tadalafil with the same protocol of G1; Group 4(G4) 98 men with VED plus Tadalafil 5mg for 3months. There were assessed at baseline and follow-up: Erectile dysfunction (ED), presence and severity of painful erections, penile plaque size and penile curvature degree. The results were evaluated at baseline and 3,6,12months. Not statistically significant differences emerged between the two groups at baseline, except for higher presence of patients with ED in in G3(7.4%) vs other groups(p < 0.001). Three months after the treatment in G3 men had a significant reduction of penile curvature degrees after 1year by treatments, whereas pain in an erection or during intercourse was resolved completely in 75% of the patients. Our study highlights that multimodal therapy has beneficial long-term effects not only in the decrease of ED symptoms, but also in the relief of the penile curvature and the quality of life.

Microvesicles-delivering Smad7 have advantages over microvesicles in suppressing fibroblast differentiation in a model of Peyronie’s disease

BackgroundThis study compared the differences of microvesicles (MVs) and microvesicles-delivering Smad7 (Smad7-MVs) on macrophage M1 polarization and fibroblast differentiation in a model of Peyronie’s disease (PD).MethodsOverexpression of Smad7 in rat BMSCs was obtained by pCMV5-Smad7 transfection. MVs were collected from rat BMSCs using ultracentrifugation. In cells, 100 µg/mL of MVs or Smad7-MVs were used to treat the 100 ng/mL of lipopolysaccharide (LPS)-induced RAW264.7 cells or 10 ng/mL of recombinant transforming growth factor-β1 (TGF-β1)-induced fibroblasts. The pro-inflammatory cytokines and markers of M1 macrophages were measured in RAW264.7 cells, and the migration and markers of fibroblast differentiation were measured in fibroblasts. In rats, 50 µg of MVs or Smad7-MVs were used to treat the TGF-β1-induced animals. The pathology of tunica albuginea (TA), the markers of M1 macrophages and fibroblast differentiation in the TA were measured.ResultsThe MVs or Smad7-MVs treatment suppressed the LPS-induced macrophage M1 polarization and TGF-β1-induced fibroblast differentiation. Moreover, the Smad7-MVs treatment decreased the fibroblast differentiation compared with the MVs treatment. In the TGF-β1-induced TA of rats, MVs or Smad7-MVs treatment ameliorated the TA fibrosis by suppressing the macrophage M1 polarization and fibroblast differentiation. There was no significance on the M1-polarized macrophages between the MVs treatment and the Smad7-MVs treatment. Meanwhile, the Smad7-MVs treatment had an edge in terms of suppressing the fibroblast differentiation in the TGF-β1-induced PD model compared with the MVs treatment.ConclusionsThis study demonstrated that Smad7-MVs treatment had advantages over MVs treatment in suppressing of fibroblast differentiation in a model of PD.