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Keywords:

  • Peyronie’s disease;
  • rabbit;
  • extracorporeal shock waves;
  • tissue injury

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES

OBJECTIVE

To develop an experimental model in rabbits to analyse the efficiency of extracorporeal shock wave therapy (ESWT) for Peyronie’s disease.

MATERIALS AND METHODS

We used 15 adult male rabbits divided into three equal groups. In group 1 (no penile ESWT) rabbits had three sessions of ESWT with 2000 shocks each (15 kV), but a rubber mat was placed between the shock head and rabbit to protect the penis; the rabbits were killed at 7 days after the last session of ESWT. In group 2 the rabbits had three sessions of ESWT using the same parameters, and were killed immediately after the last session to analyse the penis. In group 3 the rabbits had three sessions of ESWT as before but were killed at 7 days after the last session, and the penile tissue analysed macroscopically and histologically.

RESULTS

The results showed clearly that the model was efficient, creating a similar situation to that when applying ESWT in the human penis. All of the rabbits in groups 2 and 3 had haematomas and diffuse petechiae after ESWT, and only four had urethral and penile bleeding. Almost all macroscopic changes disappeared after 48 h and only one rabbit in group 3 after 7 days had a haematoma on the dorsal penile surface. The histology (assessed using haematoxylin and eosin staining) of the cavernous body of the penis showed: unchanged histology in group 1; in group 2 there was a dilated and congested vascular space in the cavernous body, with interstitial extensive bleeding in the dermis; and in group 3 there was an increase in interstitial fibrous tissue in the cavernous septum, with deposition of collagen fibres and thickening of the tunica albuginea.

CONCLUSION

The present model was efficient in producing tissue injury in the normal penis when treated with ESWT, suggesting that this promising model should be considered for use future studies of Peyronie’s disease.


Abbreviation
ESWT

extracorporeal shock wave therapy.

INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES

Peyronie’s disease is an acquired inflammatory condition of the penis associated with penile curvature and, in some cases, pain. It primarily affects men aged 45–60 years, although an age range of 18–80 years has been reported. If left untreated Peyronie’s disease can cause fibrotic, non-expansile thickening of relatively discrete areas of the corpora tunica, typically resulting in focal bend, pain or other functional or structural abnormalities of the erect penis.

Many cases resolve with no treatment; medical therapies, including antioxidants (e.g. vitamin E and potassium aminobenzoate) and corticosteroids injected directly into the plaque, lack adequate scientific support for their widespread use. Surgery remains the mainstay when conservative measures fail [1–3].

Among many alternative therapies for the surgical treatment for Peyronie’s disease extracorporeal shock wave therapy (ESWT) has been used increasingly, and analysing published results it seems to have an effect on penile pain during erection and on improvements in sexual function. Other authors report a reduction in plaque size and penile curvature [4].

Nevertheless, to date no studies have provided evidence that there is damage to normal corpus cavernosum around the fibrotic plaque, or if new plaques occur on the top of tunica albuginea, considering that currently the most accepted hypothesis for the cause of Peyronie’s disease is repeated trauma to the tunica albuginea during sexual intercourse [4].

Thus the objective of the present study was to develop an experimental model in rabbits, to analyse the efficiency of ESWT in provoking tissue injury in the normal penis when exposed to ESWT.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES

The study was approved by the Ethics Committee of the São Paulo University of Medicine. The study comprised 15 adults male rabbits (New Zealand White); a device was developed to support the rabbits in front of the ESWT equipment, and the rabbits were divided into three equal groups: group I (no penile ESWT) had three sessions of ESWT (2000 shocks each, 15 kV) and a rubber mat was placed between the shock head and the penis, to protect it from exposure. The rabbits were killed 7 days after the last session of ESWT. In group 2 the rabbits also had three sessions of ESWT (same conditions) but with no protection, and immediately after the last session they were killed and their penises analysed. In group 3 the rabbits were also exposed in the same way to ESWT, but were killed 7 days after the last session.

All rabbits were treated while under anaesthesia with ketamine 50 mg/mg and xylazine 10 mg/kg. The rabbits were killed humanely with high doses of the same drugs until cardiorespiratory arrest. The penile tissue was immediately removed for macroscopic and histological analysis.

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES

The results showed clearly that the model was efficient, creating in the laboratory a similar situation to that applying after ESWT in the human penis. All of the rabbits in groups 2 and 3 had haematomas and diffuse petechiae after the sessions of ESWT, and only four had urethral and penile bleeding (Fig. 1a,b). Almost all macroscopic changes disappeared after 48 h and only one rabbit in group 3 at 7 days had an haematoma on the dorsal penis (Fig. 1c).

image

Figure 1. The rabbit penis before (a), and after (b) ESWT, with a penis from group 3 with haematoma at 7 days (c).

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The histology (assessed by haematoxylin and eosin staining of sections) of the cavernous body showed unchanged histology in group 1 (Fig. 2a), a dilated and congested vascular space of the cavernous body, with interstitial extensive bleeding in the dermis, in group 2 (Fig. 2b), and in group 3 an increase in interstitial fibrous tissue in the cavernous septum, with deposition of collagen fibre and thickening of the tunica albuginea (Fig. 2c).

image

Figure 2. Penises from: a , group 1, with unchanged histology; b , group 2, with interstitial extensive bleeding in the dermis; and c , group 3, showing an increase in interstitial fibrous tissue in the cavernous septum, with deposition of collagen fibre and thickening of the tunica albuginea.

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DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES

Peyronie’s disease affects the quality of life of both patients and partners, and causes much psychological distress [5–7], usually as a result of the ensuing penile curvature. Surgical correction of the deformity and/or plaque is considered the ‘gold standard’ for treating Peyronie’s disease, but it has some disadvantages [8,9]. Some reduction in penile length and de novo erectile dysfunction are not uncommon after surgery, and can therefore produce an unsatisfactory outcome. As a result, several conservative or minimally invasive treatments have been tried, i.e. oral agents like colchicine, tamoxifen, potassium p-amino benzoate and vitamin E, or intralesional injections of mercury and iodide, steroids, verapamil and clostridial collagenase [10–12].

ESWT seems to be a simple and safe alternative for treating Peyronie’s disease [13]. The mechanism of action involved in ESWT for Peyronie’s disease is unclear, but there are two hypotheses: one is that there is direct damage to the penile plaque, and the other is that ESWT increases the vascularity of the area by generating heat, which leads to the induction of an inflammatory reaction, resulting in lysis of the plaque and removal by macrophages [14,15].

Hauck et al.[4]established, in a meta-analysis of 17 studies, that the optimum energy/shock wave was 15–18 kV and therefore we chose the initial level for the present study, to assess possible histological changes with a minimum energy applied.

There are many reports showing good results of ESWT for relieving pain during erection and improving sexual function [4]. It seems that pain resolves faster after ESWT than during the natural course of the disease. The effect on plaque size and penile curvature is less impressive.

Husain et al.[15] showed that 60% of their patients treated with ESWT had relief of pain and 47% had a decrease in penile curvature during a follow-up of 19 months. Claro et al.[16] reported an improvement in penile angulation (64%), with a mean reduction of 21°, when using vitamin E in high doses associated with ESWT. There were no major complications to ESWT in these studies. Petechiae, skin haematoma, penile bruising and urethral bleeding were the only complications, and they always resolved spontaneously [15,16]. Only one study has reported the effect of ESWT on the penis of the rat; this controlled study in a rat model showed no differences in effects on haemodynamic and histopathological variables between the group treated by ESWT and a control group [17].

In conclusion, we showed that the present rabbit model was efficient in producing tissue injury in the normal penis when exposed to ESWT, and suggest that this promising model be considered for use future studies of Peyronie’s disease.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES