Search

Transforming growth factor-β1 (TGF-β1) has been identified as one of the most important fibrogenic cytokines associated with Peyronie's disease (PD). The mothers against decapentaplegic homolog 7 (SMAD7) is an inhibitory Smad protein that blocks TGF-β signaling pathway. The aim of this study was to examine the anti-fibrotic effect of the SMAD7 gene in primary fibroblasts derived from human PD plaques. PD fibroblasts were pretreated with the SMAD7 gene and then stimulated with TGF-β1. Treated fibroblasts were used for Western blotting, fluorescent immunocytochemistry, hydroxyproline determination, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assays. Overexpression of the SMAD7 gene inhibited TGF-β1-induced phosphorylation and nuclear translocation of SMAD2 and SMAD3, transdifferentiation of fibroblasts into myofibroblasts, and quashed TGF-β1-induced production of extracellular matrix protein and hydroxyproline. Overexpression of the SMAD7 gene decreased the expression of cyclin D1 (a positive cell cycle regulator) and induced the expression of poly (ADP-ribose) polymerase 1, which is known to terminate Smad-mediated transcription, in PD fibroblasts. These findings suggest that the blocking of the TGF-β pathway by use of SMAD7 may be a promising therapeutic strategy for the treatment of PD.

The pathophysiology of LaPeyronie's disease (PD) is considered to be multifactorial, involving genetic predisposition, trauma, inflammation and altered wound healing. However, these factors have not yet been validated using animal models. In this study, we have presented a new model obtained by tunica albuginea allograft. A total of 40, 16-week-old male rats were used. Of these, 8 rats served as controls and underwent a 10 × 2-mm-wide tunical excision with subsequent autografting, whereas the remaining 32 underwent the same excision with grafting of the defect with another rat's tunica. Morphological and functional testing was performed at 1, 3, 7 and 12 weeks after grafting. Intracavernous pressure, the degree of penile curvature and elastic fiber length were evaluated for comparison between the allograft and control groups. The tissues were obtained for histological examination. The penile curvature was significantly greater in the allografted rats as compared with the control rats. The erectile function was maintained in all rats, except in those assessed at 12 weeks. The elastin fiber length was decreased in the allografted tunica as compared to control. SMAD2 expression was detected in the inner part of the allograft, and both collagen-II- and osteocalcin-positive cells were also noted. Tunica albuginea (TA) allograft in rats is an excellent model of PD. The persistence of curvature beyond 12 weeks and the presence of ossification in the inner layer of the TA were similar to those observed in men with PD. Validation studies using this animal model would aid understanding of the PD pathophysiology for effective therapeutic interventions.

Epigenetic modifications, such as histone acetylation/deacetylation, have been shown to play a role in the pathogenesis of fibrotic disease. Peyronie's disease (PD) is a localized fibrotic process of the tunica albuginea, which leads to penile deformity. This study was undertaken to determine the anti-fibrotic effect of small interfering RNA (siRNA)-mediated silencing of histone deacetylase 2 (HDAC2) in primary fibroblasts derived from human PD plaque. PD fibroblasts were pre-treated with HDAC2 siRNA and then stimulated with transforming growth factor-β1 (TGF-β1). Protein was extracted from treated fibroblasts for Western blotting and the membranes were probed with antibody to phospho-Smad2/Smad2, phospho-Smad3/Smad3, smooth muscle α-actin and extracellular matrix proteins, including plasminogen activator inhibitor-1, fibronectin, collagen I and collagen IV. 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 in fibroblasts. Knockdown of HDAC2 in PD fibroblasts abrogated TGF-β1-induced extracellular matrix production by blocking TGF-β1-induced phosphorylation and nuclear translocation of Smad2 and Smad3, and by inhibiting TGF-β1-induced transdifferentiation of fibroblasts into myofibroblasts. Decoding the individual function of the HDAC isoforms by use of siRNA technology, preferably siRNA for HDAC2, may lead to the development of specific and safe epigenetic therapies for PD.

The surgical techniques used by Austoni and Egydio in the treatment of Peyronie's disease are based on geometric principles. The aim of this paper is to report our multicentric experience and technical changes to Austoni's original technique, focusing on several tips and tricks to make this technique easy to perform, even by less experienced practitioners. We performed operations in three different Italian institutions. We implanted a small soft Virilis I® axial prostheses (Ø 7 Fr.), using a bovine pericardium collagen matrix patch (Hydrix®) to cover the defect in the tunica albuginea. Sixty patients with a mean age of 58 years (range 44-76 years) underwent surgery between September 2005 and January 2010. After surgery, mean lengthening of the shaft was 2 cm (range 1.2-2.3 cm) with complete correction of penile recurvatum. Thirty-nine patients resumed sexual activity 60 days later, 14 after 90 days and 7 after 120 days. The international index of erectile function (IIEF) score was 15.5 before surgery and it improved to 23 at 12 and 24 months after surgery. Furthermore, the visual analogue scale (VAS) showed good results in terms of the recovery of natural sexual intercourse (over 80% of couples) and of the original length and girth of the penis. The soft implant we used takes advantage of erection that occurs spontaneously, using the residual erection of the spared cavernous tissue. The method is easy to learn and reproducible, and the use of pericardium speeds up the operation, while also covering large defects of the tunica albuginea that result from complex recurvatum.

The long-term outcomes of 157 patients affected by Peyronie's disease (PD) who underwent penile straightening with Egydio's technique between January 2004 and December 2008 are reported. Only patients with PD who were stable for at least 6-12 months prior to surgery were enrolled in this study. Preoperative assessment included a dynamic echo colour Doppler ultrasound scan to evaluate the degree of penile deformity and the peak systolic velocity in the cavernosal arteries and an assessment of erectile function with the administration of the International Index of Erectile Function 5 (IIEF-5) questionnaire. Stretched penile length was recorded pre- and postoperatively. Surgical complications, cosmesis and sexual function, patient satisfaction and postoperative erectile function were assessed postoperatively at 3 months, 1 year and 2 years, respectively. After a median follow-up period of 20 months (range: 12-24 months), we found that mild residual curvature (12%) and glans hypoesthesia (3%) were the only causes of partial dissatisfaction. No rejection of the graft was observed. All patients recovered their ability to penetrate with no difficulty. In addition, an intraoperative average increase of 2.5 cm (range: 1.7-4.1 cm) in stretched penile length was recorded, with all patients engaging in penetrative sexual intercourse. In conclusion, this procedure represents a safe and reproducible technique for the correction of penile curvature resulting from PD and yields excellent cosmetic and functional results.

The aim of this article is to analyse the long-term results of different surgical techniques for correction of penile deviations in Peyronie's disease. Patients who underwent surgery for a penile deviation in Peyronie's disease between 1997 and 2007 were included into this study. Cases were retrospectively analysed by chart review. The current situation was evaluated by a 16-item standardized questionnaire addressing penile straightness, sensation, length, sexual function and satisfaction. Ninety patients were contacted with a return rate of 75 (83%) evaluable questionnaires. Thirty-two patients were operated by shortening techniques (STs) with either Schroeder-Essed (n=16) or Nesbit (n=16). Forty-three were operated by a plaque in-/excision and defect covering by TachoSil method (TM). Both groups were similar regarding age (ST 56 years, TM 57 years), comorbidities, mean preoperative erection hardness score (EHS; 3.1 ST, 3.4 TM) and time of follow-up (total mean, 63 months). Preoperatively ST patients had significantly less plaques (P<0.05) and a lower deviation angle in comparison to TM patients (ST 56° versus TM 74°; P< 0.001). Still TM patients reported slightly better straightening results, but a significantly lower mean EHS (ST 3.3 versus TM 2.6; P<0.001) during the follow-up. Satisfaction rates were similar in both groups. In conclusion, both techniques revealed to be safe and sustainable successful in penile straightening with better functional outcome of patients operated by STs.

Aim: To discuss important points on medical history, preoperative evaluation, real expectations, and selection of the appropriate surgical procedure to improve patient satisfaction after surgical procedures for Peyronie's disease., Methods: Recent advances in approaches to Peyronie's disease are discussed based on the literature and personal experiences. Issues concerning surgical indication, patient selection, surgical techniques, and grafting are discussed. Lengthening procedures on the convex side of the penile curvature by means of grafting offer the best possible gain from a reconstruction standpoint. Penile rectification and rigidity are required to achieve a completely functional penis. Most patients experience associated erectile dysfunction (ED), and penile straightening alone may not be enough to restore complete function. Twenty-five patients were submitted to total penile reconstruction on length and girth with concomitant penile prosthesis implant. The maximum length restoration was possible and limited by the length of the dissected neurovascular bundle. The mean age was 55.4 years (32-69 years) and the mean angle of curvature 74.2+/-22.4 degree (0-100 degree). Pericardial grafting was used to cover the defect. The mean follow-up time was 11.2 +/- 5.9 months (3-22 months)., Results: Mean functional penile length gain was 3.40+/-0.73 cm (2-5 cm). Penile prosthesis maintained the penis straight. No infections occurred. Sexual intercourse was restored in all patients and all reported recovered self-esteem., Conclusion: Improving patient satisfaction with the surgical treatment includes proper preoperative evaluation on stable disease, penile shortening, vascular and erectile status, patient decision and selection as well as extensive discussion on surgical technique for restoring functional penis (length and rigidity). Length and girth restoration is very important for self-esteem and patient satisfaction.

Aim: Erectile dysfunction may be observed in up to 80% of patients with Peyronie's disease. An objective evaluation of the erectile function is attempted to work out in patients with Peyronie's disease., Methods: Penile deformity, sexual function and penile vascular status were analyzed in 123 patients with Peyronie's disease, who had not received any pertinent treatment., Results: Penile deformity, palpable plaque and pain on erection were seen in 112 (91%), 97 (78.8%) and 27 (21.9%) of the 123 patients, respectively. Of the 76 patients evaluated by color Doppler ultrasounography, veno-occlusive dysfunction as the vascular component for erectile dysfunction was found in 17 (22.3%), arterial insufficiency in 10 (13.1%) and a mixed picture in 23 (30.2%)., Conclusion: The documentation of penile erectile function and the determination of the vascular status using color Doppler ultrasonography can guide the appropriate therapeutic choice.