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Functional tissue engineering of autologous tunica albuginea: a possible graft for Peyronie's disease surgery.

OBJECTIVES: The aim of the present study was to generate a tissue engineered type of mechanically stable graft suitable for surgical replacement of the tunica albuginea penis. METHODS: Porcine fibroblasts isolated from open fascia biopsies were seeded on decellularized collagen matrices and then cultivated in a bioreactor under continuous multiaxial stress for up to 21 days (n=12). Static cultures without mechanical stress served as controls. Cell proliferation, cell alignment, and de novo synthesis of extracellular matrix proteins (proteoglycans, procollagen I, elastin) in these grafts was evaluated by hematoxylin-eosin, pentachrome, and immuno-staining. Additionally, the enzymatic isolation of porcine fibroblasts from X4mm skin punch biopsies (n=8) was evaluated. RESULTS: Mechanically strained cultures of fibroblasts showed a homogeneous multilayer matrix infiltration and a regular cell alignment in the direction of strain axis after 7 days, as well as a de novo production of extracellular matrix proteins compared to the static control. A large amount of viable fibroblasts was easily obtained from small skin punch biopsies. CONCLUSION: This study shows that continuous multiaxial stimuli improve proliferation and extracellular matrix synthesis of mature fibroblasts reseeded on a biological matrix making this a feasible autologous tissue engineered graft for penile surgery. For the clinical setting fibroblasts harvested from small skin biopsies can be a comfortable cell source.

Animals↗

Straightening corporoplasty for Peyronie's disease: a review of 218 patients with median follow-up of 89 months.

OBJECTIVE: To evaluate the outcome at long term follow-up after straightening corporoplasty of penile curvature due to Peyronie's disease. METHODS: Between 1986 and 2001 a total of 279 patients with Peyronie's disease were operated on using the Nesbit procedure. We were able to obtain complete follow-up data in 218 patients. The follow-up data included evaluation of complete correction of the curvature, penile shortening, sexual function, complications and subjective patient satisfaction. RESULTS: After a median follow-up of 89 months subjective patient determination of satisfaction indicated that 83.5% were completely satisfied with the results of surgery. Complete correction of the penis was obtained in 86.3% of the patients. One hundred and ninety patients (87.1%) had good erectile function (IIEF-5 >21). Shortening of the penis (from 1.5 to more than 3 cm) occurred in 38 patients (17.4%), but only in 5 (2.3%) was intercourse difficult because of excessive shortening. Major sensory changes, confined to the glans area, were reported by 24 patients (11%). CONCLUSION: The Nesbit operation is a simple and safe technique to correct the penile deformity due to Peyronie's disease. This technique results in the greatest amount of patient satisfaction about erectile function. The procedure can be used to correct all degrees of penile curvature successfully except for the short penis. Informed consent should be amply discussed before operating in regard to the risk of penile shortening and major sensory changes of the glans area.

Follow-Up Studies↗

Alpha-1-antitrypsin levels and genetic variation of the alpha-1-antitrypsin gene in Peyronie's disease.

OBJECTIVES: Alpha-1-antitrypsin (alpha1-antitrypsin) is a major protease inhibitor controlling tissue degradation. Reduced alpha1-antitrypsin levels could result in a change of collagen metabolism. Previous studies have described decreased alpha1-antitrypsin levels in patients with Peyronie's disease. However, only a small number of patients were analyzed, and the reason for the decreased alpha1-antitrypsin levels remained unclear. This study investigated prospectively the levels of alpha1-antitrypsin in patients with Peyronie's disease, as well as genetic variation in the coding region of the alpha1-antitrypsin gene. METHODS: Alpha1-antitrypsin levels were determined prospectively in 94 patients with Peyronie's disease and compared to healthy controls. Analysis of the alpha1-antitrypsin gene (S, Z variants; single nucleotid polymorphisms [SNPs]: T-395A, M2, M3, G6118A) was done in 141 Peyronie's patients including 43 patients with investigated alpha1-antitrypsin serum levels and compared to healthy controls. RESULTS: In patients with Peyronie's disease, the alpha1-antitrypsin levels seemed to be decreased significantly compared to healthy controls. However, in the age matched approach no significant differences occurred. Moreover, a significant (p < 0.002) decrease of the alpha1-antitrypsin level with increasing age was observed, explaining the initial differences between the two groups. In confirmation with these findings, no significant association of the alpha1-antitrypsin gene variants with Peyronie's disease was detectable. CONCLUSIONS: The results of this study do not indicate a significant association between Peyronie's disease and decreased alpha1-antitrypsin levels. Low alpha1-antitrypsin levels in Peyronie's patients are, rather, an age-related phenomenon, as revealed by the comparison with aged matched healthy controls. The decrease of the alpha1-antitrypsin serum level with increasing age has not been described before.

Adolescent↗

Potassium paraaminobenzoate (POTABA) in the treatment of Peyronie's disease: a prospective, placebo-controlled, randomized study.

PURPOSE: The aim of this study was to investigate the effect of potassium paraaminobenzoate (Potaba) in Peyronie's disease in a prospective, randomized, double-blind, placebo-controlled, multicentre study during a 12-months period of treatment. PATIENTS AND METHODS: 103 patients with Peyronie's disease and a history <12 months, non-calcified plaques and without pre-treatment were included. 51 were randomized to potassium paraaminobenzoate, 52 to placebo receiving 4 x 3g/day for 12 months. Follow-up was performed during the treatment period. Response has been defined as regression in plaque-size and/or reduction in penile curvature of at least 30%. Data analysis was focussed on 75 patients who completed the study [valid-cases (VC)]. RESULTS: No severe adverse events occurred. Response rates were 74.3% on potassium paraaminobenzoate and 50.0% on placebo (p=0.016). Mean plaque-size decreased from 259 mm(2) to 142 mm(2) in the treatment arm. In the placebo group, plaque-size aggravated from 259 mm(2) to 303 mm(2) after 6 months but improved slightly to 233 mm(2) after 12 months. Differences between the groups were significant (p=0.042). Pre-existing curvature did not improve under the drug (p=0.066) but comparing the development of new curvature or deterioration of pre-existing curvature under potassium paraaminobenzoate penile deviation remained stable. However, under placebo penile curvature deteriorated significantly in 32.5% of the cases (p<0.001). No significant differences concerning decrease of pain could be observed between the two groups (82.6% vs. 77.3%). CONCLUSIONS: The results of this study indicate a significant plaque-related effect of potassium paraaminobenzoate. There was no relevant difference with regard to improvement of pre-existing penile deviation. However, under potassium paraaminobenzoate a significant protective effect on deterioration of penile curvature could be demonstrated. Potassium paraaminobenzoate appears to be useful to stabilize the disorder and prevent progression of penile curvature.

4-Aminobenzoic Acid↗

Liposomal recombinant human superoxide dismutase for the treatment of Peyronie's disease: a randomized placebo-controlled double-blind prospective clinical study.

OBJECTIVE: To demonstrate the efficacy and safety of a topical gel containing liposomally encapsulated recombinant human Superoxide Dismutase (lrhSOD) in the treatment of painful Peyronie's Disease. The theoretical background is that lrhSOD, by scavenging of free oxygen radicals, might interrupt inflammatory cascades and thereby limit further disease progression. METHODS: In a placebo-controlled randomized clinical trial, 39 patients with Peyronie's Disease and significant pain symptoms were treated with lrhSOD or placebo for a 4 week period. At this time, statistical evaluation of pain resolution was performed as primary study endpoint. Patients then were continued in a cross-over study design to ensure a total of 8 weeks of lrhSOD therapy for all study participants. Pain, plaque and curvature assessment was performed at study entry and every 4 weeks until week 12. RESULTS: LrhSOD treatment resulted in a statistically significant reduction of pain (p=0.017) compared to placebo already after 4 weeks. At week 12 pain was significantly reduced in 89% of patients who all had received 8 weeks of lrhSOD therapy at that time. Response to other disease parameters was assessed at week 12: plaque size was reduced in 47% of patients, as was plaque consistence in 38%. Penile curvature was improved at 5-30 degrees in 23% of patients. The expected spontaneous disease progression rate of up to 40%, as reported by several investigators, was significantly reduced to <10% under lrhSOD therapy, and patients satisfaction was high, also consequent to the lack of therapy-related side effects observed in the present study. CONCLUSION: LrhSOD is an easily administrable, safe and effective local therapeutic for the painful phase of Peyronie's Disease.

Cross-Over Studies↗

Prevalence of Peyronie's disease among patients with erectile dysfunction.

PURPOSE: To assess the prevalence of Peyronie's disease (PD) among patients with erectile dysfunction (ED). MATERIALS AND METHODS: A total of 1,440 male patients with ED were enrolled in this study. Patients were interviewed for ED using the International Index of Erectile Function (IIEF). All patients were also screened for socio-demographic data and risk factors for ED that included age, smoking, diabetes, hypertension, dyslipidemia, Ischemic Heart Disease (IHD), and psychological disorders. The diagnosis of PD was based on a palpable penile plaque or acquired penile curvature. Patients underwent routine laboratory investigation in addition to testosterone and prolactin assessment. RESULTS: Mean ages +/-SD were 54.1 +/- 6.9 (range 42-71) and 52.5 +/- 11.9 (range 20-84) years for patients with and without PD respectively. Of the patients, 11.8% had mild, 38.3% had moderate and 49.9% had severe ED. 7.9% of the patients had PD. Significant associations between PD and both the longer duration and the increased severity of ED were detected. There were also significant associations between PD and the following socio-demographic risk factors of ED: age, obesity, smoking, duration and number of cigarettes smoked per day. Concomitant diseases and medical comorbidities such as diabetes, dyslipidemia, psychological disorders and the presence of at least one risk factor were significantly associated with PD in patients with ED. CONCLUSIONS: Peyronie's disease was not rare among the study population. There were significant associations between ED risk factors and PD. Further studies are needed to investigate how much ED and PD influence each other.

Adult↗

A critical analysis of nonsurgical treatment of Peyronie's disease.

OBJECTIVE: Because the efficacy of nonsurgical therapy of Peyronie's disease is controversial, this review analyses the current status of conservative therapy of Peyronie's disease. METHOD: A systematic survey on results of studies published as original papers in peer-reviewed journals is provided. RESULTS: Oral drug therapies include potassium para-aminobenzoate (Potaba), vitamin E, colchicine, tamoxifen, propoleum, acetyl-L-carnitine, and propionyl-L-carnitine. Verapamil, interferon-alpha2a and interferon-alpha2b, collagenase, cortisone, hyaluronidase, and superoxide dismutase are considered intralesional therapies that have had various degrees of success. Other treatments include local gels, iontophoresis, extracorporeal shock wave therapy, and radiation. CONCLUSION: This review analyses the current status of the conservative therapy of Peyronie's disease, because the efficacy of the nonsurgical therapy is controversial.

Administration, Oral↗

Alterations in the transforming growth factor (TGF)-beta pathway as a potential factor in the pathogenesis of Peyronie's disease.

OBJECTIVES: The development of fibrotic diseases is associated with alterations in the transforming growth factor beta (TGF-beta) pathway. We have investigated the expression and activity of Smad transcription factors of the TGF-beta pathway in primary tunical fibroblasts derived from patients with Peyronie's disease and from controls. METHODS: Primary fibroblasts were established from biopsies obtained from plaques of 16 patients with Peyronie's disease or the tunica albuginea of 8 control patients. The expression and activity of Smad transcription factors in control and TGF-beta-stimulated primary fibroblasts were investigated at the RNA and protein level by reverse transcription-polymerase chain reaction, Western blotting, and immunofluorescence. RESULTS: RNA expression levels of Smad3 and Smad4 were significantly increased in fibroblasts from patients with Peyronie's disease. When stimulated with TGF-beta1, fibroblasts showed rapid nuclear translocation of Smad2/3, as soon as 15 min after stimulation. This effect was more pronounced and exhibited an earlier onset in fibroblasts from patients with Peyronie's disease, compared with controls. In addition, an increased nuclear retention time of Smad4 was observed in fibroblasts from patients with Peyronie's disease. CONCLUSIONS: The expression and activity of Smad transcription factors of the TGF-beta pathway is increased in fibroblasts of patients with Peyronie's disease. Alterations in the TGF-beta pathway seem to be a pathogenetic factor in the development of Peyronie's disease.

Cell Nucleus↗

Systematic evidence-based analysis of plaque injection therapy for Peyronie's disease.

OBJECTIVE: We evaluated the peer-reviewed urology literature for intraplaque injection of medication for Peyronie's disease and assessed the quality of studies via rigorous evidence-based medicine criteria. METHODS: We performed a search of peer-reviewed literature looking at all agents used to treat Peyronie's disease by intraplaque injections. These were then evaluated using the Oxford Centre for Evidence-Based Medicine criteria, which ranks studies from strongest (level 1) to weakest (level 5) strength of evidence. RESULTS: Of the 19 studies found involving injection therapy for Peyronie's disease, 17 showed positive results. Six studies using injectable corticosteroids were identified and though all showed positive results, they were of level 4 quality. Two collagenase injection studies (one level 4 and one level 2 study) were identified, both of which showed positive results. All four verapamil injection studies found (three level 4 and one level 2 study) showed positive results. Seven papers involving interferon alpha2-beta injections were evaluated (six level 4 and one level 1 study), five of which showed positive outcomes and two of which showed no significant benefit. CONCLUSIONS: Ninety percent of the studies regarding Peyronie's disease showed positive outcomes. Unfortunately, most of these have not offered convincing evidence-based data, with only one positive study meeting level 1 Oxford criteria for clinical efficacy. Standardised outcome measures were not used, making comparisons difficult. These results reveal the need for the development of validated outcome measures and well-designed controlled trials to determine optimal therapeutic intervention for this disorder.

Adrenal Cortex Hormones↗

Porcine small intestinal submucosa is not an ideal graft material for Peyronie's disease surgery.

PURPOSE: The incidence of Peyronie's disease is up to 7% in some series. While there are numerous nonsurgical methods of treatment, they do not have a high rate of success. Nesbit plication was once the accepted surgery for Peyronie's disease. Tunical lengthening procedures became popular because they avoided penile shortening caused by the Nesbit procedure. More urologists now perform plaque incision or excision, followed by grafting with different materials. Small intestinal submucosa offered promise as an ideal graft material. It is available off the shelf as 1 or 4-ply graft material. In several studies it appeared to function as a collagen based scaffold with graft incorporation in host tissue. MATERIALS AND METHODS: A single reconstructive urologist performed plaque incision and small intestinal submucosa grafting in 4 cases of Peyronie's disease using the same surgical technique. RESULTS: Although early results were positive, we have achieved less than satisfactory results with this material. The penis was straight in the immediate postoperative period but there was recurrent curvature in 3 of the 4 patients, of whom 2 had recurrence within 4 months of the procedure. CONCLUSIONS: We observed disappointing results with small intestinal submucosa for Peyronie's disease surgery with a high percent of recurrent curvature. Further studies are needed to determine if 1 or 4-ply small intestinal submucosa is an ideal graft material for the tunica albuginea.

Animals↗

Isolated septal fibrosis or hematoma--atypical Peyronie's disease?

PURPOSE: Classically Peyronie's disease presents with penile curvature and/or pain, and is associated with a palpable penile plaque. We frequently examine patients with suspected Peyronie's disease ultrasonographically and have noted a subset of patients in whom we could identify only a circumscribed septal lesion. We identified characteristics of these patients. MATERIALS AND METHODS: Of our series of approximately 650 patients with Peyronie's disease 47 were identified with these lesions. RESULTS: Of the 47 patients 22 presented with penile curvature with or without accompanying or preceding pain. Of the 47 patients 17 had a significant history of trauma, although only had the classic stigmata of penile fracture. A total of 16 patients had no history of curvature, 7 presented with only penile shortening or focal lack of rigidity and 5 were incidentally found to have lesions during assessment for other complaints. Three patients presenting after trauma were noted to have septal liquefied hematomas, which we aspirated under ultrasound guidance. Followup ultrasound revealed minimal septal thickening. In 1 of these patients the hematoma was adjacent to more typical-appearing septal fibrosis. CONCLUSIONS: We theorize that these hematomas are due to septal fractures and may represent a forme fruste or possibly a precursor lesion of more typical septal fibrosis. Ultrasonographic evaluation may allow earlier identification and treatment of occult septal injuries or lesions and prevent subsequent fibrosis and its associated symptoms.

Adult↗