Intracavernosal Prostaglandin E1 Research Articles

(036) The Comparison of an Efficacy and Safety of Geometrical Principles Based Corporoplasty Combined with Intraoperative Intracavernosal Prostaglandin E1 Injections and the Non-Geometrical Surgical Techniques for Peyronie's Curvature Correction

Abstract Introduction There is a lack of research evidence and properly conducted comparative long-term studies in regards to whether the intra and post-operative safety and efficacy of geometrical principle of plaque incision and grafting technique, especially if combined with an intraoperative intracavernosal prostaglandin E1 (PGE1) injection instead of saline, is better than the non-geometrical techniques. Objective The aim of this retrospective study was to present our 8-year single-center experience of surgical management of Peyronie's disease in the means of efficacy and safety by comparing geometrical principle of plaque incision and grafting technique combined with the intraoperative intracavernosal PGE1 injection with the other non-geometrical surgical techniques used at our centre for the treatment of penile curvature. Methods Our andrology centre approved this retrospective study and commenced an audit in order to obtain anonymised data. In total 70 patients underwent non-geometrical surgical techniques based penile curvature correction between 2014 and 2017. All the surgeries were carried out performing the intraoperative intracavernosal PGE1 injection instead of obtaining saline-induced erection. The demographic data was retrieved and a comparative analysis was performed. Results In total 216 (N=216) patients, aged 42–73 years old (average age 59 years) suffering from Peyronie's disease had surgical treatment of the curvature at our centre from 2014 to 2023. Group 1 (G1) patients accounted for 32.41% (N=70) of total patients - they were 46–78 years old (average age 64 years) and underwent non-geometrical principals based surgery for Peyronie's disease in between 2014 and 2017. Group 2 (G2) patients accounted for 68.52% (N=148) of total patients - they underwent the surgery using plaque's incision and grafting technique based on geometrical principles in between 2018 and 2023. 31 patients (44.3%) out of G1 required additional curvature corrections after an initial surgery, but only 3 patients (2.0%) out of G2 required that. Preoperative dorsal penile curvature degree among G1 was 50° - 100° (the mean degree 70°) and 60° - 110° (the mean degree 78°) among G2. 11 patients (15.7%) out of G1 and 15 patients (10.1%) out of G2 had the combined dorsolateral curvature. 3 patients (4.3%) out of G1 and 6 patients (4.1%) out of G2 had ventral curvature. 9 patients (12.9%) out G1 and 2 patients (1.4%) out of G2 have reported a subjective statement of their penile shaft appearing shorter after the curvature correcting surgery. 2 patients (2.9%) out G1 and 1 patient (0.7%) out of G2 have reported a subjective statement of erectile dysfunction post the surgery. There were no intraoperative or postoperative complications associated with the intracavernosal PGE1 injection. Conclusions In summary, we found that plaque's incision and grafting technique based on geometrical principles was advantageous against the other non-geometrical penile curvature surgical techniques due to better efficiency achieved by the higher initial success rates that require an additional correction almost twice less often. We also revealed that the intracavernosal PGE1 injection was a safe and sufficient method for inducing erection intraoperatively, that had not been associated with any complications and maintained the good outcomes of the surgical Peyornie's disease treatment. Disclosure No.

Accuracy of MRI without intracavernosal prostaglandin E1 injection in staging, preoperative evaluation, and operative planning of penile cancer.

To evaluate the performance of non-erectile MRI in staging and preoperative evaluation of penile carcinomas, compared to postoperative histopathology. In this retrospective study, MRI scansof patients who had undergone surgery for penile carcinoma (n = 54) between January 2012 and April 2018 were read by two radiologists; anddisagreement was solved in the presence of a third experienced radiologist. Data necessary for preoperative evaluation and staging were collected and compared with final postoperative histology and the type ofsurgery performed. All MRI had been performed without intracavernosal injection of prostaglandin E1 and with IV Gadolinium, as per local protocol. 54 patients were included in the study (mean age 57.52 ± 12.78). The number of patients with T1, T2, and T3 staging in histopathology were 32, 14, and 8. Moderate interobserver agreement was found for staging, disease-free penile length, and all subsites except urethra, which had weak agreement. Strong agreement of consensus MRI with final histopathological staging was found (49/54, weighted κ = 0.85), with high sensitivity and specificity. Sensitivity and specificity for involvement of corpus spongiosum, corpora cavernosa, and urethra were 95.5% and 93.8%, 87.5% and 97.8%, and 90.9% and 86.1%, respectively. Sensitivity (89.6%) and specificity (100%) of MRI for predicting adequate disease-free penile length were high. There were acceptable interobserver agreement and good diagnostic performance of MRI for staging and preoperative assessment without intracavernosal injection, especially for higher stages and higher degrees of invasion which require more extensive surgery.

Intracavernosal prostaglandin E1 self vs office injection therapy in patients with erectile dysfunction

We have investigated the reliability of intracavernosal prostaglandin E1 (PGE1) office vs self-injection therapy in patients with erectile dysfunction (ED). A total of 298 male patients with ED were enrolled in this study. In all patients, intracavernosal titration of the PGE1 dose was performed. A total of 106 patients were enrolled in the self-injection program, and 192 patients were enrolled in the office injection program. There were significant differences between number of injections and amount of PGE1 per month, total number of injections, and total amount of PGE1 on office and self-injection programs (P < 0.05 for each). There was a significant increase in the dropout rate in the office injection group compared with the self-injection group (P < 0.05). There was an increase in penile fibrosis in the self-injection program compared with the office program (P < 0.05). A self-injection program is reliable. Office injection program can be reserved for a subset of ED patients with special preferences.

Aetiology and Management of Male Erectile Dysfunction and Female Sexual Dysfunction in Patients with Cardiovascular Disease

The historical basis for understanding erectile function as a neurovascular phenomenon and the advance from fanciful to effective treatment of erectile dysfunction (ED) are reviewed, with emphasis on patients with cardiovascular disease (CVD). ED occurs in 60% of CVD patients by 40 years of age. Male ED and female sexual dysfunction (FSD) diminish quality of life and often warn of occult CVD. ED is often unrecognised but is readily diagnosed during a 5-minute interview using a truncated International Index of Erectile Function questionnaire. Erection of the penis and clitoral engorgement result from local, arousal-induced release of neuronal and endothelial-derived nitric oxide (NO). Arterial vasodilatation and relaxation of cavernosal smooth muscle cells cause arterial blood to flood trabecular spaces, compressing venous drainage, resulting in tumescence. Cyclic guanosine monophosphate (cGMP)-induced activation of protein kinase G mediates the effects of NO by enhancing calcium sequestration and activating large-conductance, calcium-sensitive K+ channels. Future treatment strategies will likely enhance these pathways. Phosphodiesterase-5 inhibitors (sildenafil, tadalafil and vardenafil) increase cGMP levels in erectile tissue. These agents are effective in 80% of CVD patients with ED and can be used safely, even in the presence of stable coronary disease or congestive heart failure, provided nitrates are avoided and patients do not have hypotension, severe aortic stenosis or evocable myocardial ischaemia. Second-line therapies (vacuum constrictor device and transurethral or intracavernosal prostaglandin E1) can also be used in CVD patients. Treatment of FSD and its relationship to CVD are less well established, but similarities to ED exist. ED can be prevented by reduction of CVD risk factors, exercise, weight loss and abstinence from smoking.

Eficacia y seguridad del sildenafilo en pacientes con disfunción eréctil e hipertensión arterial. Factores pronósticos de respuesta

Our purpose was to assess the efficacy and safety of sildenafil as a treatment for erectile dysfunction in hypertensive patients, and to investigate those factors associated with a treatment failure. Open, prospective study including 114 patients suffering from erectile dysfunction plus arterial hypertension who were evaluated by anamnesis, physical examination, blood tests including glycemia and lipidic and hormonal profiles, penile colour Doppler ultrasonography after intracavernosal prostaglandin E1 (PGE1) injection, and the Sexual Health Inventory for Men (SHIM). Efficacy of sildenafil was assessed by administering again the SHIM and by means of a global assessment questionnaire. Side effects were also recorded. Factors influencing treatment outcome were evaluated by univariate and multivariate statistical analysis. Overall, sildenafil was effective in 59.2% of 103 eligible patients. Efficacy in patients with psychogenic erectile dysfunction was 75%, whereas in those with an organic etiology, the efficacy was 50.7%. Age, diabetes mellitus, nocturnal penile tumescence, response to intracavernosal PGE1 injection and erectile dysfunction severity (defined by the SHIM basal score) significantly influenced treatment response (p < 0.05) after an univariate analysis. The multivariate analysis, however, selected only diabetes mellitus and severity of erectile dysfunction as the prognostic factors. No severe side effects were noticed. Sildenafil is a rather effective and well-tolerated treatment for erectile dysfunction in hypertensive patients. Baseline severity of erectile dysfunction and diabetes mellitus represent the prognostic factors most significantly associated with treatment outcome.

Synergistic effects of sildenafil on relaxation of rabbit and rat cavernosal smooth muscles when combined with various vasoactive agents.

To evaluate which vasoactive agents have synergistic effects on the cavernosal smooth muscles of rabbits and rats when the agents are combined with sildenafil. Relaxation responses of cavernosal smooth muscle to single agents (phentolamine, moxisylyte, sodium nitroprusside, forskolin, vasoactive intestinal peptide, VIP, papaverine and sildenafil) in the rabbit, and prostaglandin-E1 and sildenafil in the rat, and to combinations of each agent plus sildenafil, were assessed in vitro. The response to sildenafil of the rabbit strips with and without incubation with l-arginine (1 mmol/L) for 20 min was also evaluated. The effective concentrations for a half-maximal response of single agents and combination solutions were compared. All single agents induced concentration-dependent relaxation of the rabbit and rat cavernosal smooth muscles. There was significant synergism on rabbit cavernosal smooth muscle when the sildenafil was combined with forskolin, sodium nitroprusside, VIP or phentolamine. There was also significant synergism with sildenafil plus prostaglandin-E1 in rat cavernosal muscles. There were no synergistic effects of combinations of sildenafil plus moxisylyte, papaverine or l-arginine. These results suggest potentially effective combined therapies of sildenafil and intraurethral or intracavernosal prostaglandin-E1, intracavernosal forskolin or VIP, or oral phentolamine for patients with erectile dysfunction who have no success after monotherapy with these agents.

Neuropathy is a major contributing factor to diabetic erectile dysfunction

Erectile dysfunction (ED) in diabetes is multifactorial. So far, the impact of neuropathy has not been well determined. This study was performed to assess the frequency of abnormal neurophysiological tests in patients with ED due to diabetes compared to patients with ED due to nondiabetic neuropathies in order to estimate the contribution of neuropathy in diabetic ED. Forty-nine men with ED were studied. We classified ED as 'diabetic', 'neuropathic' or 'ED of other origin'. 26.6% of the men fulfilled the criteria of diabetic ED, 42.9% had neuropathic ED. In every patient history taking, a questionnaire focusing on autonomic symptoms other than ED, clinical examination, nerve conduction studies (NCS), sphincter ani electromyography (EMG), heart rate variability testing (HRV) and quantitative sensory testing (QST) was performed. Vascular function was assessed by the intracavernosal prostaglandin E1 (PGE1) injection test. The frequency of abnormal results in diabetic and neuropathic patients was compared. Vascular function was abnormal in only one patient with diabetic ED and three patients with neuropathic ED. Both groups had similar frequencies of autonomic symptoms other than ED (64% in diabetic vs. 64% in neuropathic patients), abnormal EMG (33% vs. 40%) and abnormal QST (vibratory perception 83% vs. 84%, cold perception 9% vs. 19%, warm perception 42% vs. 43%). Abnormal clinical findings (50% vs. 33%), NCS (75% vs. 50%) and HRV (39% vs. 25%) were slightly, but not significantly more frequent in men with diabetic ED than neuropathic ED. The tests indicating neuropathy showed abnormalities in men with diabetic ED as frequently as in men with neuropathic ED. Some tests even suggested neuropathy more often in diabetic than in neuropathic ED. The findings support the hypothesis that neuropathy contributes significantly to the pathophysiology of ED in diabetes mellitus. [Neurol Res 2001; 23: 651-654]

The Effect of Cryosurgical Ablation of the Prostate on Erectile Dysfunction

Objective To investigate the incidence and identify the possible cause of erectile dysfunction after cryoablation of the prostate. Patients and methods Erectile function was examined prospectively in 15 sexually active men (aged 59–72 years) who underwent cryoablation of the prostate for clinically localized prostate cancer. Erectile function was assessed before and 6 months after treatment; after intracavernosal injection with 10 μg of prostaglandin E1 (PGE1), the degree and duration of erection, the size of the cavernosal arteries, the penile arterial blood flow velocity, and the time to achieve peak flow were evaluated using high-resolution ultrasonography and colour pulsed-Doppler spectral analysis. Results Post-operatively, all patients initially reported an inability to achieve an erection sufficient for vaginal intercourse. At 6 months′ follow-up, erectile dysfunction persisted in nine, with minimal or no response to the intracavernosal PGE1 injections, there was a significant decrease in the peak velocity of blood flow within cavernosal arteries and a significant increase in the time to achieve peak arterial flow. Conclusion Although many factors may contribute to erectile dysfunction after cryoablation of the prostate, vascular injury plays a major role.

Vasoactive intestinal polypeptide and phentolamine mesylate administered by autoinjector in the treatment of patients with erectile dysfunction resistant to other intracavernosal agents.

To study the effect of vasoactive intestinal polypeptide (VIP) and phentolamine mesylate (PM) on patients in whom previous intracavernosal therapy had failed. The study comprised 70 consecutive patients attending a clinic for erectile dysfunction, in whom previous therapy with intracavernosal prostaglandin-E1 (20 microg and papaverine (30 mg) combined with 1 mg PM had failed. They were given intracavernosal injections, initially with 25 microg VIP/1 mg PM (VIP1) and if unsuccessful, 25 microg VIP/2 mg PM (VIP2). Both VIP1 and VIP2 were administered using a pre-filled ready-to-use autoinjector fitted with a 29 G needle. The patients were diagnosed as having spinal cord lesion (eight), diabetes (21), ischaemic heart disease (12), hypertension (six), other diagnoses (nine), or idiopathic causes (14). Forty-seven (67%) of patients achieved erections sufficient for sexual intercourse (33 on VIP1 and 14 on VIP2), initially under clinical supervision and subsequently during home use. Minor side-effects were transient facial flushing in 37 (53%), truncal flushing in six (9%), bruising in 14 (20%) and pain from the injection needle in eight (11%). No patients reported priapism or other serious adverse events. The combination of VIP and PM at the dose used was a safe and effective treatment in patients in whom other therapies had failed.

Penile fibrosis in intracavernosal prostaglandin E1 injection therapy for erectile dysfunction.

Penile fibrosis (PF) may be a complication of intracavernosal injection therapy (ICI). It has been well documented as a side effect of papaverine, but there have been few reports associating penile fibrosis with prostaglandin E1 (PGE1, Alprostadil). Many authors did not find fibrotic changes in the penis while others reported penile fibrosis as a complication of intracavernosal PGE1 in only 0.76-2.1% of their patients. Recent studies, however, suggest that the incidence may be as high as 15%. Three hundred consecutive patients who returned to our Institute for repeat prescription of PGE1 were asked about penile curvature and deformity and the penis was examined for fibrotic change. Twenty-two were excluded because of concurrent or previous use of papaverine and/or phentolamine, 30 patients had pre-ICI evidence of fibrotic change and 3 had incomplete data. Of the remaining 245 patients, 57 (23.3%) were found to have penile fibrosis. These men, mean age 62 y (21-79), had been self injecting an average of 5.2 times per month (1-16) for an average period of 29.2 months (2-86). The mean dose of PGE1 used was 13 micrograms (2-60) and an average of 65.6 micrograms of PGE1 (3-360) was used per month. The mean total number of injections was 142.4 (8-810) and the mean total amount of PGE1 1703 micrograms (105-11,520). Penile fibrosis is hence a significant complication of intracavernosal PGE1 therapy. It is mandatory to examine patients methodically for fibrotic changes in the penis prior to commencement of treatment and at subsequent regular reviews. Patients should be specifically warned of the possibility of penile fibrosis and should be instructed on self examination so that they may report early changes if and when these occur.

The effect of cryosurgical ablation of the prostate on erectile function.

To investigate the incidence and identify the possible cause of erectile dysfunction after cryoablation of the prostate. Erectile function was examined prospectively in 15 sexually active men (aged 59-72 years) who underwent cryoablation of the prostate for clinically localized prostate cancer. Erectile function was assessed before and 6 months after treatment; after intracavernosal injection with 10 micrograms of prostaglandin E1 (PGE1), the degree and duration of erection, the size of the cavernosal arteries, the penile arterial blood flow velocity, and the time to achieve peak flow were evaluated using high-resolution ultrasonography and colour pulsed-Doppler spectral analysis. Post-operatively, all patients initially reported an inability to achieve an erection sufficient for vaginal intercourse. At 6 months' follow-up, erectile dysfunction persisted in nine, with minimal or no response to the intracavernosal PGE1 injections, there was a significant decrease in the peak velocity of blood flow within cavernosal arteries and a significant increase in the time to achieve peak arterial flow. Although many factors may contribute to erectile dysfunction after cryoablation of the prostate, vascular injury plays a major role.

Intraurethral prostaglandin E-2 cream: A possible alternative treatment for erectile dysfunction

Prostaglandin E-2 (PGE-2) is an oxytocic agent in suppository form with vasodilatory effects similar to prostaglandin E-1 (PGE-1). Because some men find intracavernosal injections disagreeable, we investigated whether intraurethral PGE-2 may provide an alternative method for treating erectile dysfunction. A PGE-2 cream was made using PGE-2 suppositories (20 mg or 40 mg), 10 cc of 2% lidocaine (Xylocaine) jelly, and 40 cc of surgical lubrication. Two cc of the cream was instilled into the urethral meatus using a syringe, the cream was massaged down the urethra, and the urethra was occluded for five minutes. Treatment response was rated as no penile tumescence, partial tumescence, and full tumescence. Overall, 70 percent showed a response and 30 percent had full penile tumescence. Two of 4 men who had no tumescence using PGE-2 had a subsequent full tumescence using intracavernosal PGE-1 (15 mg), while 3 of 4 men with a partial tumescence with PGE-2 had a subsequent full tumescence using intracavernosal PGE-1 (15 mg). These data demonstrate that full penile tumescence may be achieved in impotent men using intraurethral PGE-2 cream. This pilot study supports the necessity for further investigations in a randomized double-blind manner in the use of intraurethral PGE-2 cream as a less invasive treatment alternative for erectile dysfunction.