1. Le onde d’urto nella disfunzione erettile: la terapia del futuro?
Marco Franco

2. Erectile funcion: the anatomical substrate
Progenitors
Progenitors
Neurons
Endothelial cells
Smooth muscle cells
Vessels
Homeostasis (Physiology)  Remodelling (Pathology)

3. Intracavernosal injections
Limits
Side effects
Lack of durable effect on the spontaneous improvement of erectile function.
“Difficult-to-treat” patients
Although the majority of ED patients can be satisfactorily treated with phosphodiesterase type 5 inhibitors (PDE5), a substantial population (30– 40%) cannot.
This includes patients who are intolerant to PDE5 inhibitors’ side effects, taking nitrate medication for angina, or having certain types of ED refractory to PDE5 inhibitors.
Intracavernosal injections
Penile implants.

4. 2013: New

6. Low Intensity ESWT (LIESWT) & Vessels The evidences
In vivo pre-clinical evidences
Non ED animal models
ED animal model
Clinical evidences on ED patients

7. Porcine model of chronic myocardial ischemia
2004
LI-ESWT
Control
Porcine model of chronic myocardial ischemia

8. Control
LI-ESWT
Collateral vessels
Coronary angiography
Ventriculography
Nishida T., et al., Circulation, 2004

9. progenitor cells (EPCs) homing
2006
SDF-1
Endothelial
progenitor cells (EPCs) homing
VEGF
Aicher A., et al., Circulation, 2006

10. N (n=8)
DM (n=8)
Streptozocin
DM + SW
(n=8)
J Sex med, 2013

11. nNOS expression
When compared with DM rats, shockwave-treated rats displayed significantly higher numbers of nNOS-positive nerves in different compartments of the erectile tissue, including the dorsal nerves, around the dorsal arteries, and in the corpora cavernosa.

12. Endothelial content
ESWT was able to significantly restore the endothelial contents in both the cavernous sinusoids and arteries compartments.

13. ESWT is able to significantly restore the smooth muscle content

14. Mesenchymal stem cells
Increased recruitment of MSCs into the erectile tissue.

15. ? ESWT Improved erectile function
Vasculogenic growth factors - chemoattractors
Mechanosensors
membrane receptor kinases,
integrins, G proteins, ion channels, intercellular junction proteins, membrane lipids (e.g.,
those associated with caveolae), and the cytoskeleton
Increased homing of precursors
Restoration of erectile tissue integrity
Neoangiogenesis
Improved erectile function

16. ESWT Cavitation Shear stress Mechanosensors Improved erectile function
Vasculogenic growth fctors - chemoattractors
Mechanosensors
membrane receptor kinases,
integrins, G proteins, ion channels, intercellular junction proteins, membrane lipids (e.g.,
those associated with caveolae), and the cytoskeleton
Increased homing of precursors
Restoration of erectile tissue integrity
Neoangiogenesis
Improved erectile function

17. Clinical evidences

19. 2010
Professor Yoram Vardi
2012
2012

20. Medispec ED 1000

23. Pilot study 20 men with vasculogenic ED The inclusion criteria:
History of ED for at least 6 mo
Abnormal 2-night nocturnal penile tumescence (NPT) parameters
PDE5-I responders
IIEF-ED domain score between 5–19.
The exclusion criteria:
Psychogenic ED (normal NPT parameters)
Any neurologic pathology
Prior radical prostatectomy, and recovery from any cancer within the past 5 yr.

24. 4-wk PDE5-I washout period
The penis was manually stretched; the shockwaves were delivered to the distal, mid,
and proximal penile shaft, and the left and right crura.
300 shocks per treatment point (1500 per session) at an energy density of 0.09 mJ/mm2 and a frequency of 120/min
IIEF = International Index of Erectile Function; QEQ = Quality of Erection Questionnaire; SEAR = Self-Esteem and Relationship Questionnaire; RS = rigidity score; NPT = nocturnal penile tumescence; FMD = flow-mediated dilatation; EDITS = Erectile Dysfunction Inventory of Treatment Satisfaction.
Vardi Y., et a., Eur Urol., 2010

25. Results High response rate (>70%)
(higher than that of any previously published placebo-controlled trial in men with ED)
Vardi Y., et a., Eur Urol., 2010

26. Enhanced penile perfusion
Results
Enhanced penile perfusion
Vardi Y., et a., Eur Urol., 2010

27. Long-term follow up
At the 3- and 6-mo follow-up examinations, 10 men reported that they had spontaneous erections that were sufficient for penetration and did not require PDE5-I support before sexual intercourse.
None of the study participants reported any pain during
the treatment and follow-up periods, and no adverse effects
were recorded.
Vardi Y., et a., Eur Urol., 2010

28. N= 20
N=40
Vardi Y., et al., The Journal of Urology, 2012

29. Ilan Gruenwald et al., J Sex Med, 2012

30. Improved penile endothelial function
Ilan Gruenwald et al., J Sex Med, 2012

31. Ongoing Clinical Trials
Extracorporeal Shock Wave Therapy With a Wide Focus Probe for the Treatment of Erectile Dysfunction
Low Intensity Extracorporeal Shock Wave Therapy for the Treatment of Erectile Dysfunction- 4 Arms
Low Intensity Shock Wave Therapy (LI-ESWT) for Erectile Dysfunction in Post Radical Prostatectomy Patients Not Responding to PDE5 Inhibitors (LI-ESWT)

32. Conclusions & Future directions

33. Intracavernosal injections
Limits
Side effects
Lack of durable effect on the spontaneous improvement of erectile function.
“Difficult-to-treat” patients
Although the majority of ED patients can be satisfactorily treated with phosphodiesterase type 5 inhibitors (PDE5), a substantial population (30– 40%) cannot.
This includes patients who are intolerant to PDE5 inhibitors’ side effects, taking nitrate medication for angina, or having certain types of ED refractory to PDE5 inhibitors.
Intracavernosal injections
Penile implants.

34. Conclusioni 1. DE Lieve – Medio 2. DE endoteliale
3. Pazienti difficili/impossibili da trattare con terapia orale
° Nitrati
° Con effetti collaterali
° Non effetti duraturi nel tempo
° Che intendono essere “curati” definitivamente
4. Ipotesi affascinante: associazione terapeutica