Association between Antenatal Vaginal Bleeding and Adverse Perinatal Outcomes in Placenta Accreta Spectrum.

Background and Objectives: Placenta accreta spectrum (PAS) disorders are placental conditions associated with significant maternal morbidity and mortality. While antenatal vaginal bleeding in the setting of PAS is common, the implications of this on overall outcomes remain unknown. Our primary objective was to identify the implications of antenatal vaginal bleeding in the setting of suspected PAS on both maternal and fetal outcomes. Materials and Methods: We performed a case-control study of patients referred to our PAS center of excellence delivered by cesarean hysterectomy from 2012 to 2022. Subsequently, antenatal vaginal bleeding episodes were quantified, and components of maternal morbidity were assessed. A maternal composite of surgical morbidity was utilized, comprised of blood loss ≥ 2 L, transfusion ≥ 4 units of blood, intensive care unit (ICU) admission, and post-operative length of stay ≥ 4 days. Results: During the time period, 135 cases of confirmed PAS were managed by cesarean hysterectomy. A total of 61/135 (45.2%) had at least one episode of bleeding antenatally, and 36 (59%) of these had two or more bleeding episodes. Increasing episodes of antenatal vaginal bleeding were associated with emergent delivery (p < 0.01), delivery at an earlier gestational age (35 vs. 34 vs. 33 weeks, p < 0.01), and increased composite maternal morbidity (76, 84, and 94%, p = 0.03). Conclusions: Antenatal vaginal bleeding in the setting of PAS is associated with increased emergent deliveries, earlier gestational ages, and maternal composite morbidity. This important antenatal event may aid in not only counseling patients but also in the coordination of multidisciplinary teams caring for these complex patients.

Sildenafil Protects Endothelial Cells From Radiation-Induced Oxidative Stress.

INTRODUCTION: The etiology of radiation-induced erectile dysfunction (ED) is complex and multifactorial, and it appears to be mainly atherogenic. AIM: To focus on vascular aspects of radiation-induced ED and to elucidate whether the protective effects of sildenafil are mediated by attenuation of oxidative stress and apoptosis in the endothelial cells. METHODS: Bovine aortic endothelial cells (BAECs), with or without pretreatment of sildenafil (5 µM at 5 minutes before radiation), were used to test endothelial dysfunction in response to external beam radiation at 10-15 Gy. Generation of reactive oxygen species (ROS) was studied. Extracellular hydrogen peroxide (H2O2) was measured using the Amplex Red assay and intracellular H2O2 using a fluorescent sensor. In addition, ROS superoxide (O2•-) was measured using a O2•- chemiluminescence enhancer. Both H2O2 and O2•- are known to reduce the bioavailability of nitric oxide, which is the most significant chemical mediator of penile erection. Generation of cellular peroxynitrite (ONOO-) was measured using a chemiluminescence assay with the PNCL probe. Subsequently, we measured the activation of acid sphingomyelinase (ASMase) enzyme by radioenzymatic assay using [14C-methylcholine] sphingomyelin as substrate, and the generation of the proapoptotic C16-ceramide was assessed using the diacylglycerol kinase assay. Endothelial cells apoptosis was measured as a readout of these cells' dysfunction. MAIN OUTCOME MEASURES: Single high-dose radiation therapy induced NADPH oxidases (NOXs) activation and ROS generation via the proapoptotic ASMase/ceramide pathway. The radio-protective effect of sildenafil on BAECs was due to inhibition of this pathway. RESULTS: Here, we demonstrate for the first time that radiation activated NOXs and induced generation of ROS in BAECs. In addition, we showed that sildenafil significantly reduced radiation-induced O2•- and as a result there was reduction in the generation of peroxynitrite in these cells. Subsequently, sildenafil protected the endothelial cells from radiation therapy-induced apoptosis. STRENGTHS AND LIMITATIONS: This is the first study demonstrating that single high-dose radiation therapy induced NOXs activation, resulting in the generation of O2•- and peroxynitrite in endothelial cells. Sildenafil reduced ROS generation by inhibiting the ASMase/ceramide pathway. These studies should be followed in an animal model of ED. CONCLUSIONS: This study demonstrated that sildenafil protects BAECs from radiation-induced oxidative stress by reducing NOX-induced ROS generation, thus resulting in decreased endothelial dysfunction. Therefore, it provides a potential mechanism to better understand the atherogenic etiology of postradiation ED. Wortel RC, Mizrachi A, Li H, et al. Sildenafil Protects Endothelial Cells From Radiation-Induced Oxidative Stress. J Sex Med 2019;16:1721-1733.

TrueNTH sexual recovery study protocol: a multi-institutional collaborative approach to developing and testing a web-based intervention for couples coping with the side-effects of prostate cancer treatment in a randomized controlled trial.

BACKGROUND: Over half of men who receive treatment for prostate suffer from a range of sexual problems that affect negatively their sexual health, sexual intimacy with their partners and their quality of life. In clinical practice, however, care for the sexual side effects of treatment is often suboptimal or unavailable. The goal of the current study is to test a web-based intervention to support the recovery of sexual intimacy of prostate cancer survivors and their partners after treatment. METHODS: The study team developed an interactive, web-based intervention, tailored to type of treatment received, relationship status (partnered/non-partnered) and sexual orientation. It consists of 10 modules, six follow the trajectory of the illness and four are theme based. They address sexual side effects, rehabilitation, psychological impacts and coaching for self-efficacy. Each includes a video to engage participants, psychoeducation and activities completed by participants on the web. Tailored strategies for identified concerns are sent by email after each module. Six of these modules will be tested in a randomized controlled trial and compared to usual care. Men with localized prostate cancer with partners will be recruited from five academic medical centers. These couples (N = 140) will be assessed prior to treatment, then 3 months and 6 months after treatment. The primary outcome will be the survivors' and partners' Global Satisfaction with Sex Life, assessed by a Patient Reported Outcome Measure Information Systems (PROMIS) measure. Secondary outcomes will include interest in sex, sexual activity, use of sexual aids, dyadic coping, knowledge about sexual recovery, grief about the loss of sexual function, and quality of life. The impact of the intervention on the couple will be assessed using the Actor-Partner Interaction Model, a mixed-effects linear regression model able to estimate both the association of partner characteristics with partner and patient outcomes and the association of patient characteristics with both outcomes. DISCUSSION: The web-based tool represents a novel approach to addressing the sexual health needs of prostate cancer survivors and their partners that-if found efficacious-will improve access to much needed specialty care in prostate cancer survivorship. TRIAL REGISTRATION: Clinicaltrials.gov registration # NCT02702453 , registered on March 3, 2016.

Impact of cardiovascular risk factors and related comorbid conditions and medical therapy reported at baseline on the treatment response to tadalafil 5 mg once-daily in men with lower urinary tract symptoms associated with benign prostatic hyperplasia: an integrated analysis of four randomised, double-blind, placebo-controlled, clinical trials.

PURPOSE: The influence of cardiovascular risk factors/comorbidities on response to oral once-daily tadalafil 5 mg was explored in men with lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH). METHODS: This post hoc analysis pooled data from four double-blind studies in which 1498 men with > 6-mo history of LUTS/BPH were randomised and received either once-daily placebo (n = 746) or tadalafil 5 mg (n = 752) for 12 weeks. Descriptive statistics were reported for changes in total International Prostate Symptom Score (IPSS), IPSS voiding and storage subscores, and IPSS quality-of-life (QoL) index. Treatment group differences by baseline clinical and cardiovascular factors and medical therapies were examined using analysis of covariance. RESULTS: Tadalafil was effective in men with LUTS/BPH and cardiovascular risk factors/comorbidities except for patients receiving > 1 antihypertensive medication. Placebo-adjusted least squares (LS) mean improvements in total IPSS were -1.2 (95% CI: -2.5 to -0.0) in men taking > 1 antihypertensive medication vs. -3.3 (95% CI: -4.4 to -2.1) in men taking one medication (interaction p = 0.020). In addition, placebo-adjusted LS mean improvements in total IPSS were -0.2 (95% CI, -2.1 to 1.7) in men who reported use of diuretics vs. -2.8 (95% CI, -3.7 to -1.9) in men who reported taking other antihypertensive medications vs. -2.3 (95% CI, -3.2 to -1.5) in men who reported not using any antihypertensive drug (p-value for interaction = 0.053). CONCLUSIONS: Once-daily tadalafil 5 mg improved LUTS/BPH, regardless of severity, in men with coexisting cardiovascular risk factors/comorbidities, except for patients with history of > 1 drug for arterial hypertension. Use of diuretics may contribute to patients' perception of a negated efficacy of tadalafil on LUTS/BPH. Comorbidities should be considered when choosing the optimal medicine to treat men with LUTS/BPH.

Laparoscopic surgery for acute neonatal appendicitis.

We present the first two cases of acute neonatal appendicitis operated on through the laparoscopic approach. Acute neonatal appendicitis is uncommon and rarely considered by clinicians when assessing the neonatal acute abdomen. Our two cases demonstrate the potential value of diagnostic laparoscopy in the acute neonatal abdomen that poses a diagnostic dilemma. Furthermore, technical modifications of well-established laparoscopic techniques in the older child enable its use in neonates as a therapeutic tool.

Peyronie's disease: urologist's knowledge base and practice patterns.

Peyronie's disease (PD) is a poorly understood clinical entity. We performed an in-depth analysis of the knowledge base and current practice patterns of urologists in the United States. A 46-question instrument was created by two experienced PD practitioners and emailed to current American Urology Association members nationally. Questions were either multiple-choice or used a visual analogue scale. Responses regarding treatment options were answered by ranking a list of utilized therapies by preference. Data were aggregated and mean values for each category compiled. Responses were received from 639 urologists (67% in private practice). Almost all (98%) reported seeing PD patients with regularity. Twenty-six percent believed PD prevalence is ≤1%, a small fraction (5%) reporting prevalence as ≥10%. Only 3% referred patients to a subspecialist in PD. Twenty-six percent believed PD is a condition that does not warrant any treatment. The preferred initial management was with oral agents (81%). Of those who used intralesional injections as first line, verapamil was most commonly selected (67%). Seventy-nine percent perform surgery for PD with 86% reporting the optimal timing at ≥12 months after onset of symptoms. Seventy percent perform penile plication, most commonly the Nesbit technique (54%), 61% perform implant surgery and 37% reported performing plaque incision/excision and grafting. Although PD is now a more recognized condition, there are still large variances in knowledge and management strategies. Prospective clinical studies are needed to elucidate standardized management guidelines and a more cohesive strategy to manage this common disease.

Ciprofloxacin-induced acute psychosis.

Ciprofloxacin, one of the fluoroquinolone antibiotics, has become one of the most widely prescribed antimicrobial agents. It is generally well tolerated with a low incidence of side effects, which are mild in nature. There is a distinct incidence of neuropsychiatric adverse effects, which include psychotic reactions. We describe a case of a woman who experienced an acute psychosis secondary to ciprofloxacin administration, which resolved on cessation of therapy. All urologists should be aware of this problem and be familiar with the recommendations for ciprofloxacin use in patients with underlying neuropsychiatric problems.

Simultaneous microsurgical vasal reconstruction and varicocele ligation: safety profile and outcomes.

OBJECTIVES: Simultaneous varicocele ligation and vasal reconstruction has previously been avoided because of concern regarding testicular devascularization. This study sought to investigate the safety of a simultaneous combined approach in the hands of an experienced microsurgeon. METHODS: A retrospective review was conducted of the records of 47 men who underwent vasal reconstruction, 10 (21%) of whom had simultaneous ligation of a clinically palpable varicocele. Specific attention was focused on the development of postoperative testicular atrophy and hydrocele and the analysis of postoperative semen parameters. RESULTS: No patient developed postoperative testicular atrophy or hydrocele. No statistically significant difference existed in postoperative seminal parameters between those patients who had vasal reconstruction alone and those who had a combined procedure. CONCLUSIONS: In the hands of an experienced microsurgeon, simultaneous vasal reconstruction and varicocele ligation is a management strategy that has an excellent safety profile. This approach is not recommended for the occasional microsurgeon.

Presence of mature sperm in testicular parenchyma of men with nonobstructive azoospermia: prevalence and predictive factors.

OBJECTIVES: Hitherto, patients with testicular dysfunction and azoospermia had to resort to adoption, donor sperm insemination, or child-free living. The realization that a proportion of such men harbor spermatozoa in their testicular parenchyma, combined with the ability of intracytoplasmic sperm injection (ICSI) to effect pregnancy with single sperm, has prompted male infertility clinicians to explore testicular sperm extraction (TESE) in this patient population. We sought to investigate the likelihood of finding spermatozoa during TESE from men presenting with nonobstructive azoospermia and to define if any factors existed that were predictive of eventual sperm presence or absence. METHODS: Thirty patients with nonobstructive azoospermia underwent TESE and simultaneous formal testis biopsy, cytologic analysis, and wet preparation analysis. Tissue obtained from TESE was analyzed according to a rigorous protocol, followed by exhaustive searching by trained embryologists. RESULTS: Twenty-one patients (70%) had spermatozoa found on testicular tissue analysis. Neither patient age nor follicle-stimulating hormone (FSH) level was predictive of the ability to find sperm. With regard to histologic pattern, 50% of men with Sertoli cell-only, 75% of patients with maturation arrest, and 100% of patients with spermatids seen on histologic analysis had sperm retrieved from their testicular tissue during TESE. Absence of sperm on cytologic smear and wet preparation analysis failed to predict the presence of sperm on formal testicular tissue analysis in 40% of patients. CONCLUSIONS: Men with nonobstructive azoospermia may have mature spermatozoa present within their testicular parenchyma. Relying on these data, patients should not be excluded from TESE based on serum FSH level, age, prior histopathologic pattern, or cytology/wet preparation results. These figures will allow clinicians to counsel patients with nonobstructive azoospermia informatively regarding TESE and their chances of having testicular sperm retrieved.

An open-label, uncontrolled dose-optimization study of sublingual apomorphine in erectile dysfunction.

BACKGROUND: Because apomorphine is a dopamine agonist that acts on areas of the central nervous system believed to mediate penile erection, its use in erectile dysfunction (ED) has been investigated. However, it also produces nausea by dopamine-receptor stimulation of the chemotrigger zone in the brain. Therefore, a low plasma concentration, achieved rapidly, would be selective for the desired erectile response but would be below the dopamine threshold for nausea. OBJECTIVE: We evaluated the efficacy and tolerability of a dose-optimized regimen of a sublingual formulation of apomorphine (apomorphine SL) in the treatment of ED. METHODS: This was a multicenter, open-label, uncontrolled, Phase III dose-optimization study of apomorphine SL in heterosexual men with ED. The 2-week screening period, during which baseline severity of ED was determined using the International Index of Erectile Function, was followed by a 3-week dose-optimization period beginning at a dose of 2 mg. Patients were to make at least 2 attempts at intercourse per week throughout the study, placing 1 apomorphine tablet under the tongue beforehand. At the end of the first week, the dose could be increased to 3 mg at the discretion of the investigator; at the end of the second week, the dose could be increased to a maximum of 4 mg or decreased as needed. In the following 4-week treatment period, patients took their individual optimal doses. The primary efficacy variable was the percentage of attempts resulting in erections firm enough for intercourse, as assessed by investigators' review of data from patients' diaries. Secondary variables included the percentage of attempts resulting in successful intercourse, time to erection, and duration of erection. Information about adverse events, including their severity and relation to treatment, was determined on the basis of direct questioning, spontaneous reports, and review of patient diaries. RESULTS: The study enrolled 849 heterosexual men whose ages ranged from 31 to 78 years (mean, 58.1 years). They had a mean 5.7-year history of ED of varbus causes. ED was mild in 11.5% of the men, moderate in 23.8 c, and severe in 48.1%. When results of the last 8 attempts were pooled, representing the period during which patients were taking their optimal doses of apomorphine SL, the mean percentage of attempts resulting in erections firm enough for intercourse was 39.4%, compared with 13.1% at baseline; attempts resulting in intercourse increased from a mean of 12.7% at baseline to 38.3% with treatment. The average median time to erection was 23 minutes, and the average median duration of erection was 13 minutes. Nausea, the most common treatment-related adverse event (11.7%). was dose related and diminished with continued dosing. One patient had a single syncopal episode that was judged to be related to apomorphine SL. CONCLUSIONS: In the present study, a dose-optimization regimen of apomorphine SL-with dosing initiated at 2 mg and adjusted up to a maximum of 4 mg as needed-was effective and well tolerated in the treatment of ED, regardless of its cause or severity.

Expanding the paradigm for plaque development in Peyronie's disease.

Despite centuries of recognition, Peyronie's disease remains somewhat of an enigma. Conventional wisdom suggests that trauma to the erect or semierect penis is the inciting event that sets off a cascade of events at the cellular level that results in localized fibrosis of the tunica albuginea. However, many questions remain unanswered at this juncture among the most important of which are why do so few men manifest this condition? Why is there such an ethnic predilection? What are the cofactors that along with penile trauma lead to plaque development. Historically, cytokine overexpression, autoimmune and genetic factors have been cited as contributors. This treatise endeavors to conduct an evidence-based assessment of the literature as it pertains to the pathophysiology of Peyronie's disease. Furthermore, an effort is made to evaluate contemporary literature pertaining to novel concepts in Peyronie's disease pathogenesis including NOS alterations, free radical generation, microarray analysis, pathogen involvement and animal model development. In conclusion, it is likely that in the near future we will see dramatic developments in our understanding of this condition.

Comparison of in-patient and out-patient penile prosthesis surgery.

Between December 1996 and December 1998, 79 inflatable penile implant insertions have been performed at our institution by a single surgeon. The objective of this analysis was to compare our in-patient and out-patient experience with penile prosthesis insertion with respect to ease of performance and complication profiles. Data was collected in a prospective manner for both groups (in-patient, n = 33 and out-patient, n = 46). The two groups were compared with respect to intra-operative blood loss, operative time, time lost from work, narcotic use and complication rates. Both groups of patients experienced similar operative blood loss, essentially identical operative times, time lost from work and narcotic use. Most importantly, overall complication rates were 6% for the in-patient group and 4% for the out-patient group. Inflatable penile implant surgery is feasible in an ambulatory surgical setting. There is no difference in complication rates, loss of time from work, or intra-operative and post-operative course. Furthermore, there is a significant saving at our institution by performing the procedure in an out-patient fashion. In-patient prosthetic surgery is reserved for secondary procedures following a prior implant infection or primary implants in men with significant co-morbidities that require in-patient postoperative monitoring.

The hemodynamics of erectile dysfunction following nerve-sparing radical retropubic prostatectomy.

OBJECTIVE: Despite the advent of the nerve-sparing radical retropubic prostatectomy (NSRRP) a significant number of men still suffer from post radical prostatectomy impotence. The purpose of this study was to investigate the pathogenesis of erectile dysfunction following NSRRP and to define the previously reported vascular mechanism. Furthermore, it was our goal to clarify the respective contributions of arterial and venous components. PATIENTS AND METHODS: Sixteen potent males with localized prostate carcinoma underwent dynamic infusion cavernosometry preoperatively to assess arterial and venous hemodynamics. Ten of these men were impotent following the operation and had repeat cavernosometric evaluation six months postoperatively. RESULTS: On cavernosometry all 10 patients had arterial insufficiency on at least one side, six patients had bilateral changes. The mean reduction in CAOP was 50% (range 30-70%). Four patients met criteria for the diagnosis of corporovenocclusive dysfunction on cavernosometry. CONCLUSIONS: These data strongly support a vascular mechanism in the genesis of post-NSRRP impotence. This mechanism is predominantly arterial in nature, but some men have a mixed pattern with both arterial and venous components. The postoperative arterial insufficiency may be the result of intraoperative injury to the accessory pudendal artery. The exact means by which CVOD develops in this situation remains unclear at this time.

Development of a mathematical model for the prediction of the area of venous leak.

Erectile dysfunction (ED) is an increasingly prevalent medical problem, affecting up to 50% of men aged between 40 and 70-y-old. Many cases are vasculogenic and some of these stem from the inability of the penis to store blood during erection due to leak into the venous system, termed corporo-venocclusive dysfunction (CVOD). The area of leakage during erection could be the most direct measure of erectile function but has not been investigated before. We have developed a simple mathematical model to determine the area of leak during erection and have tested it on data from both normal men (n=3) and men with venogenic impotence (n=16) undergoing dynamic infusion cavernosometry (DIC). The area of leak in the impotent group is significantly greater than in normal men at intracorporal pressures above 30 mmHg and reaches a plateau between 60 and 90 mmHg. Based on this study, we suggest that it may be necessary only to perform DIC at intracorporal pressures between 60 and 90 mmHg.

Congruence between veno-occlusive parameters during dynamic infusion cavernosometry: assessing the need for cavernosography.

While dynamic infusion cavernosometry (DIC) is being performed with increasing rarity, some centers continue to use this investigation modality. Cavernosography may be utilized to identify the location of patent venous channels in men with venous leak. In an era when venous ligation surgery is being performed with less frequency, the role of cavernosography has been questioned. This study was conducted to define the congruence between the three parameters (flow-to-maintain (FTM), pressure decay (PD) and cavernosography) used in the diagnosis of venous leak during DIC. Established values for the three parameters were utilized and the diagnosis of venous leak was based upon the FTM measurement. All studies were performed using a vasoactive agent-redosing schedule. Cavernosography was conducted using a nonionic contrast agent at an intracorporal pressure of 90 mmHg. In patients with an elevated FTM value, 24% had a normal PD recorded, all of whom had FTM values <10 ml/min. The Pearson correlation coefficient for the relationship between FTM and PD was 0.58 (P=0.025). In all, 36 patients (54%) had an abnormal cavernosogram (CG). All patients who had positive findings on CG had elevated FTM values. On the other hand, 46% of patients with abnormal FTM values had a normal CG. This analysis indicates that almost one-half of men with venous leak diagnosed at the time of DIC based on FTM measurement will fail to have any veins visualized on cavernosography. These data further undermine the value of cavernosography, particularly in men with low-grade venous leak.

Peyronie's disease cell culture models: phenotypic, genotypic and functional analyses.

Peyronie's disease is a fibromatosis of the tunica albuginea. While trauma is believed to be the inciting event, the exact pathophysiology of this condition is unknown. In vitro analysis of cell biology can shed light on the pathogenesis of medical conditions and has been used for many decades as a research tool. We have established a cell culture model, which we have used to study the pathobiology of cells derived from Peyronie's disease plaque tissue. In 10 separate cell cultures derived from different individuals, these cells have demonstrated consistent phenotypic, genotypic and functional alterations. In neither of the control cell cultures, neonatal foreskin fibroblasts and normal tunica-derived fibroblasts have any of the above aberrations been demonstrated. The cells studied have been shown to be fibroblasts in nature with a sub-population of myofibroblasts present in culture. The Peyronie's disease plaque tissue-derived fibroblasts have demonstrated (i) consistent morphologic transformation (ii) increased S-phase on flow cytometry (iii) decreased dependence on culture medium (iv) cytogenic instability (v) excess production of fibrogenic cytokines and (vi) stabilization and dysfunctionalization of p53. Further refinement of this model and future analyses may permit an increased understanding of the pathogenesis of this condition and allow the development of therapeutic strategies.

Perturbation of cell cycle regulators in Peyronie's disease.

Peyronie's disease is a fibromatosis of the tunica albuginea, characterized by development of a plaque consisting primarily of collagen. It has been suggested that trauma to the erect penis is the inciting event. More recent research has focused on the cellular events leading to the dysregulated wound healing and plaque formation. Previous work has shown chromosomal aneusomies and this combined with an increased S-phase in plaque derived cell cultures suggests a perturbation in the cell cycle in this condition. The p53 protein has been shown to be an important cell cycle regulator and pro-apoptotic factor. Aberrant p53 function leading to cell immortalization and proliferation has been implicated in several human malignancies. We hypothesized that abnormal p53 function may explain the high proliferative ability of fibroblasts derived from Peyronie's plaques. This study was undertaken to study the presence and function of p53 and its downstream elements (p21, mdm-2) in Peyronie's disease cell cultures. Plaque-derived fibroblasts have been established in culture and characterized. These cells and control neonatal foreskin fibroblasts were subjected to 5 Gy of gamma radiation to induce DNA damage. After fixation, antibodies to p53 and its transcriptional elements were used to stain irradiated and non-irradiated cells and levels of p53, p21 and mdm-2 were quantified using combined immunofluorescence and flow cytometry. Non-irradiated plaque fibroblasts demonstrated the presence of p53, p21 and mdm-2 at baseline. In control foreskin fibroblasts no p53 or mdm-2 were detectable at baseline. In irradiated foreskin-derived cells significant changes in all elements were demonstrated indicating a fully functional p53 pathway and cell cycle checkpoint system in these cells. In contrast, plaque-derived cells showed no such alterations in levels of cell cycle regulators following irradiation. This is highly suggestive of an aberration of the p53 pathway in plaque-derived fibroblasts. Peyronie's plaque-derived fibroblasts demonstrated stabilization and defunctionalization of p53 protein combined with appropriate responses of its transcriptional elements. These findings may explain the high cell proliferation rates in these cells and suggests a role for perturbation of the p53 pathway in the pathogenesis of Peyronie's disease.