Boaz Appel

Can low-intensity extracorporeal shockwave therapy improve erectile function? A 6-month follow-up pilot study in patients with organic erectile dysfunction.

BACKGROUND Low-intensity extracorporeal shockwave therapy (LI-ESWT) is currently under investigation regarding its ability to promote neovascularization in different organs. OBJECTIVE To evaluate the effect of LI-ESWT on men with erectile dysfunction (ED) who have previously responded to oral phosphodiesterase type 5 inhibitors (PDE5-I). DESIGN, SETTING, AND PARTICIPANTS We screened 20 men with vasculogenic ED who had International Index of Erectile Function ED (IIEF-ED) domain scores between 5-19 (average: 13.5) and abnormal nocturnal penile tumescence (NPT) parameters. Shockwave therapy comprised two treatment sessions per week for 3 wk, which were repeated after a 3-wk no-treatment interval. INTERVENTION LI-ESWT was applied to the penile shaft and crura at five different sites. MEASUREMENTS Assessment of erectile function was performed at screening and at 1 mo after the end of the two treatment sessions using validated sexual function questionnaires, NPT parameters, and penile and systemic endothelial function testing. The IIEF-ED questionnaire was answered at the 3- and 6-mo follow-up examinations. RESULTS AND LIMITATIONS We treated 20 middle-aged men (average age: 56.1 yr) with vasculogenic ED (mean duration: 34.7 mo). Eighteen had cardiovascular risk factors. At 1 mo follow-up, significant increases in IIEF-ED domain scores were recorded in all men (20.9 +/- 5.8 vs 13.5+/- 4.1, p<0.001); these remained unchanged at 6 mo. Moreover, significant increases in the duration of erection and penile rigidity, and significant improvement in penile endothelial function were demonstrated. Ten men did not require any PDE5-I therapy after 6-mo follow-up. No pain was reported from the treatment and no adverse events were noted during follow-up. CONCLUSIONS This is the first study that assessed the efficacy of LI-ESWT for ED. This approach was tolerable and effective, suggesting a physiologic impact on cavernosal hemodynamics. Its main advantages are the potential to improve erectile function and to contribute to penile rehabilitation without pharmacotherapy. The short-term results are promising, yet demand further evaluation with larger sham-control cohorts and longer follow-up.

Low-Intensity Extracorporeal Shock Wave Therapy—A Novel Effective Treatment for Erectile Dysfunction in Severe ED Patients Who Respond Poorly to PDE5 Inhibitor Therapy

INTRODUCTION Low-intensity shock wave therapy (LI-ESWT) has been reported as an effective treatment in men with mild and moderate erectile dysfunction (ED). AIM The aim of this study is to determine the efficacy of LI-ESWT in severe ED patients who were poor responders to phosphodiesterase type 5 inhibitor (PDE5i) therapy. METHODS This was an open-label single-arm prospective study on ED patients with an erection hardness score (EHS) ≤ 2 at baseline. The protocol comprised two treatment sessions per week for 3 weeks, which were repeated after a 3-week no-treatment interval. Patients were followed at 1 month (FU1), and only then an active PDE5i medication was provided for an additional month until final follow-up visit (FU2). At each treatment session, LI-ESWT was applied on the penile shaft and crus at five different anatomical sites (300 shocks, 0.09 mJ/mm(2) intensity at 120 shocks/min). Each subject underwent a full baseline assessment of erectile function using validated questionnaires and objective penile hemodynamic testing before and after LI-ESWT. MAIN OUTCOME MEASURES Outcome measures used are changes in the International Index of Erectile Function-erectile function domain (IIEF-ED) scores, the EHS measurement, and the three parameters of penile hemodynamics and endothelial function. RESULTS Twenty-nine men (mean age of 61.3) completed the study. Their mean IIEF-ED scores increased from 8.8 ± 1 (baseline) to 12.3 ± 1 at FU1 (P = 0.035). At FU2 (on active PDE5i treatment), their IIEF-ED further increased to 18.8 ± 1 (P < 0.0001), and 72.4% (P < 0.0001) reached an EHS of ≥ 3 (allowing full sexual intercourse). A significant improvement (P = 0.0001) in penile hemodynamics was detected after treatment and this improvement significantly correlated with increases in the IIEF-ED (P < 0.05). No noteworthy adverse events were reported. CONCLUSIONS Penile LI-ESWT is a new modality that has the potential to treat a subgroup of severe ED patients. These preliminary data need to be reconfirmed by multicenter sham control studies in a larger group of ED patients.

The potential efficacy of 3,3'-diindolylmethane in prevention of prostate cancer development.

The objective of this study was to examine the efficacy of 3,3′-diindolylmethane (DIM) in prevention of prostate cancer tumor development in an animal model. Mouse prostate cancer cells (TRAMP-C2, 2×10−6) were injected subcutaneously into three groups of C57BL/6 mice (10 mice in each group). Two groups were treated earlier with DIM; 2 or 10 mg/kg each, and an additional control group was injected with medium. Animals were treated for five more weeks until sacrificed. Tumor sizes were measured biweekly. At the end of the experiment, mice were sacrificed, and tumors were excised, weighed, measured and tested using immunohistochemical studies. In addition blood samples were collected for biochemical analysis. The results indicated that DIM significantly reduced tumor development in treated animals when compared with controls. Tumors developed in 80% of controls and 40% and 60% of animals treated with 10 or 2 mg/kg of DIM, respectively. Moreover, tumors that developed in treated animals were significantly (P<0.001) smaller than in controls. Additionally, our results indicated that DIM has no effect on animal weight or liver and kidney functions. These results indicated that the DIM agent is not toxic and has an in-vivo preventive effect against the development of prostate cancer in a mouse model.

Effect of Chronic Sildenafil Treatment on Penile Endothelial Function: A Randomized, Double-Blind, Placebo Controlled Study

PURPOSE Although the effect of phosphodiesterase type 5 inhibitors on endothelial function in the systemic circulation has been extensively studied, its effect on penile endothelial function remains unexplored. Therefore, we evaluated the effect of daily sildenafil on penile endothelial function. MATERIALS AND METHODS A total of 60 patients with erectile dysfunction were randomized blindly to daily placebo or 50 mg sildenafil for 4 weeks. Penile and forearm blood flow as well as endothelial function indices were measured at baseline and after 4 weeks using venoocclusive strain gauge plethysmography for both organs. Sequential changes in flow, maximal blood flow and area under the curve induced by reactive hyperemia after 5 minutes of transient ischemia were considered indices of endothelial function. RESULTS There were 34 patients treated with sildenafil and 19 on placebo who completed the study. The general characteristics of both groups were comparable. Mean +/- SEM baseline penile blood flow was 6.2 +/- 1.4 and 7.0 +/- 0.6 ml/dl per minute for the placebo and sildenafil groups, respectively (p = 0.54). Baseline forearm blood flow was similar in both groups. At baseline penile AUC was 420 +/- 50 and 520 +/- 50 (p = 0.18), and in the forearm it was 445 +/- 40 and 410 +/- 40 (p = 0.45) for the placebo and sildenafil groups, respectively. After 4 weeks on the assigned drug penile blood flow increased to 11.2 +/- 2 ml/dl per minute in the sildenafil group (p = 0.02) and remained unchanged in the placebo group. After 4 weeks penile AUC increased to 720 +/- 65 in the sildenafil group (0.04) and remained unchanged in the placebo group. Placebo and sildenafil did not affect the indices of forearm endothelial function. CONCLUSIONS Daily sildenafil significantly improves penile blood flow and penile endothelial function indices without causing any relevant systemic effects.

Penile low-intensity shock wave therapy: a promising novel modality for erectile dysfunction.

Penile extracorporeal low-intensity shock wave therapy (LIST) to the penis has recently emerged as a novel and promising modality in the treatment of erectile dysfunction (ED). LIST has angiogenic properties and stimulates neovascularization. If applied to the corpora cavernosa, LIST can improve penile blood flow and endothelial function. In a series of clinical trials, including randomized double-blind sham-controlled studies, LIST has been shown to have a substantial effect on penile hemodynamics and erectile function in patients with vasculogenic ED. LIST is effective in patients who are responsive to phosphodiesterase 5 inhibitors (PDE5i) and can also convert PDE5i nonresponders to responders. The response to LIST wanes gradually over time, and after 2 years, about half of the patients maintain their function. Extensive research is needed to understand the effect of LIST on erectile tissue, to modify the treatment protocol to maximize its outcomes, and to identify the patients who will benefit the most from this treatment.

Low Intensity Shock Wave Treatment for Erectile Dysfunction—How Long Does the Effect Last?

Purpose: We studied the long‐term efficacy of penile low intensity shock wave treatment 2 years after an initially successful outcome. Materials and Methods: Men with a successful outcome of low intensity shock wave treatment according to the minimal clinically important difference on the IIEF‐EF (International Index of Erectile Function‐Erectile Function) questionnaire were followed at 6, 12, 18 and 24 months. Efficacy was assessed by the IIEF‐EF. Failure during followup was defined as a decrease in the IIEF‐EF below the minimal clinically important difference. Results: We screened a total of 156 patients who underwent the same treatment protocol but participated in different clinical studies. At 1 month treatment was successful in 99 patients (63.5%). During followup a gradual decrease in efficacy was observed. The beneficial effect was maintained after 2 years in only 53 of the 99 patients (53.5%) in whom success was initially achieved. Patients with severe erectile dysfunction were prone to earlier failure than those with nonsevere erectile dysfunction. During the 2‐year followup the effect of low intensity shock wave treatment was lost in all patients with diabetes who had severe erectile dysfunction at baseline. On the other hand, patients with milder forms of erectile dysfunction without diabetes had a 76% chance that the beneficial effect of low intensity shock wave treatment would be preserved after 2 years. Conclusions: Low intensity shock wave treatment is effective in the short term but treatment efficacy was maintained after 2 years in only half of the patients. In patients with milder forms of erectile dysfunction the beneficial effect is more likely to be preserved.

Transcutaneous neuromuscular electrical stimulation may be beneficial in the treatment of premature ejaculation

Approximately 20-30% of sexually active men suffer from Premature Ejaculation (PE), but the pathophysiology still remains unclear and the current available treatments for PE are unsatisfying. Considering the role of rhythmic bulbospongiosus and ischiocavernosus Muscles contractions on the ejaculatory reflex, we hypothesize that weakening this muscles via inhibiting its contractions by Application of Neuromuscular Electrical Stimulation prior to the planned sexual activity, may have a beneficial effect in the treatment of PE. Using miniaturized perineal on-demand stimulation device, in a home setting during sexual intercourse may become the first line of treatment for PE.

Patients with Elevated versus Non-Elevated Prostate Specific Antigen Levels before Suprapubic Prostatectomy: Long-Term Postoperative Follow-Up and Risk for Rising Prostate Specific Antigen and Detection of Prostate Cancer

Objective: Prostate specific antigen (PSA) is one of the most widely applied tumor markers in oncology. The marker is, however, not cancer-specific and may be elevated under other conditions. As prostate cancer may develop after surgery for benign prostate hyperplasia, postoperative follow-up of serum PSA levels is suggested in patients with at least a 10 year life expectancy. We evaluated the preoperative and monitored postoperative serum PSA levels in men who underwent suprapubic prostatectomy (SPP) for benign prostate hyperplasia, and specifically examined the rate of cancer detection in patients who had a non-elevated versus elevated age-related preoperative PSA. Patients and Methods: Two hundred and ninety-two patients who presented with benign histopathology after SPP, completed postoperative follow-up. Of those, 101 patients were found to have elevated preoperative PSA levels and a negative transrectal biopsy before the operation. The other group included 191 patients with preoperative PSA within age related limits. Results: PSA levels continued to be elevated in 11.8% of patients in the elevated PSA group compared with 3.5% in the non-elevated PSA group. Incidental surgical specimen cancer detection rate was 7 (6.5%) and 3 (1.5%) whereas follow-up cancer detection rate was 4 (3.9%) and zero in the elevated PSA group and non-elevated PSA group, respectively. In a logistic regression model, 2 factors were found to be statistically significant: age – the older the patient undergoing the operation, the greater was the likelihood to develop malignancy on follow-up. The second factor was the ratio between preoperative and postoperative PSA (prePSA – postPSA)/prePSA. Conclusions: This study is the first to compare long-term follow-up in patients after SPP with preoperative elevated PSA levels to those who have normal preoperative levels. The first group was found to have an increased risk incidental cancer in the surgical specimen, and of elevated PSA levels and eventually development prostate cancer upon follow-up.