Coil Embolization Is Not Justified for Treating Patients with Veno-Occlusive Dysfunction: Case Series and Narrative Literature Review.

Introduction: Herein, we explore whether coil embolization (CE) is effective in treating veno-occlusive dysfunction (VOD). We present five cases with seven CE episodes and a narrative literature review. Methods: From 2013 to 2018, refractory impotence prompted five men to seek penile vascular stripping (PVS), although seven CE episodes were included. All received dual cavernosography in which erection-related veins and VOD were documented. PVS entailed the venous stripping of one deep dorsal vein and two cavernosal veins. The abridged five-item version of the International Index of Erectile Function (IIEF-5) score system and the erection hardness scale (EHS) were used, and yearly postoperative follow-ups were conducted via the Internet. Using Pub Med, a narrative literature review was performed on CE treatment for VOD or varicocele. Results: Inserted coils were scattered along the erection-related veins, including the deep dorsal veins (n = 4), periprostatic plexus (n = 5), iliac vein (n = 5), right pulmonary artery (n = 2), left pulmonary artery (n = 2), and right ventricle (n = 1). PVS resulted in some improvements in the IIEF-5 score and EHS scale. Six articles highly recommend CE treatment for VOD. All claimed it is a minimally invasive effective treatment for varicocele. Conclusions: CE is not justified as a VOD treatment, regardless of its viability in the treatment of varicocele.

Emergent Penile Venous Stripping for Treating Adolescent Impotence.

INTRODUCTION: Traditional anatomy-based penile venous surgery is deemed inadequate. Based on revolutionary insights into penile vasculature, penile venous stripping (PVS) shows promise in treating adolescent erectile dysfunction (AED). We aimed to report on this novel approach. METHODS: We conducted a retrospective analysis of 223 individuals under 30 diagnosed with veno-occlusive dysfunction (VOD) between 2009 and 2023. Among them, 83 were diagnosed with AED and divided into the PVS (n = 37) and no-surgery (NS, n = 46) groups. All participants had been dissatisfied with conventional therapeutic options. Dual pharmaco-cavernosography was the primary diagnostic modality. PVS involved stripping the deep dorsal vein and two cavernosal veins after securing each emissary's vein with a 6-0 nylon suture. Erection restoration was accessed using the abridged five-item version of the International Index of Erectile Function (IIEF-5) score system and the erection hardness scale (EHS). Statistical analysis was performed using IBM SPSS 21.0. RESULTS: There were significant differences (both p < 0.001) between the preoperative and postoperative IIEF-5 scores in the PVS and NS groups (9.8 ± 3.0 vs. 20.4 ± 2.2; 9.9 ± 2.5 vs. 9.5 ± 2.1), as well as in the EHS scores (1.7 ± 0.7 vs. 3.5 ± 0.6 and 1.8 ± 0.5 vs. 1.3 ± 0.4). The satisfaction rate was 87.9% (29/33) in the PVS group and 16.7% (17/41) in the NS group. CONCLUSIONS: AED can be effectively treated using physiological methods, although larger patient cohorts are needed for validation.

A case report of right cardiac ventricle perforation by uncontrolled embolization coil inserted for treating penile veno-occlusive dysfunction.

Coil embolization (CE) is believed effective-safe for treating penile veno-occlusive dysfunction (VOD). From 2012 to 2016, refractory impotence prompted four men to seek further treatment, although they underwent six CEs elsewhere. Uncontrolled coils scattered along penile drainage veins including the deep dorsal veins (n = 3), periprostatic plexus (n = 1), iliac vein (n = 1), right pulmonary artery (n = 2), left pulmonary artery (n = 1), and right ventricle (n = 1). The last one occurred in a 40-year-old house builder, and the coil perforated the right ventricle wall and diaphragm 18 months later. Given no sustainable improvement, CE's safety and efficacy are unreliable for treating patients with VOD.

Cavernous smooth muscles: innovative potential therapies are promising for an unrevealed clinical diagnosis.

While erectile dysfunction (ED) is highly prevalent worldwide, unrevealed cavernous smooth muscles (CSM) defects can confound the diagnosis of vascular ED and lead to failure of treatments. Currently, the first-line oral treatment for ED is phosphodiesterase type 5 inhibitors (PDE5Is). Patients with diabetes mellitus (DM), those who have undergone a radical prostatectomy (RP), and the elderly population are difficult to treat by the PDE5Is; unrevealed CSM defects can result in corporo veno-occlusive dysfunction (CVOD); and penile veno-ligation surgeries are currently abandoned due to high failure rates. It has been found that gene and stem cell therapies, among others, reduce cavernous tissue apoptosis and fibrosis and can specifically target CSM defects such as the nitric oxide (NO)-mediated signaling pathway, Rho-ROCK system, and transformation growth factor (TGF)-ß1/angiotensin II (Ang II) pathway, in several laboratory animals. Current data clarify the need of diagnostic techniques that can provide an initial assessment of CSM. This assessment should be essential before giving a diagnosis of vascular ED and before applying several tests searching for a specific CSM defect to guide the specific therapy. Moreover, while patients with corporal fibrosis would fail the current medical therapies, these patients can benefit from the stem cell-based therapies that induce the internal mechanisms of tissue repair. However, penile elastography can determine the stiffness of tissues and corpus cavernosum electromyography (CC-EMG) can assess the integrated activity of CSM bulk, further refinements are required for these techniques before being considered in the evaluation of patients with ED. In conclusion, on the basis of the current scientific research, it may be possible to formulate new therapies and achieve the appropriate selection of patients who can benefit from these therapies.

Surgical niche for the treatment of erectile dysfunction.

Penile erection implicates arterial inflow, sinusoidal relaxation and corporoveno-occlusive function. By far the most widely recognized vascular etiologies responsible for organic erectile dysfunction can be divided into arterial insufficiency, corporoveno-occlusive dysfunction or mixed type, with corporoveno-occlusive dysfunction representing the most common finding. In arteriogenic erectile dysfunction, corpora cavernosa show lower oxygen tension, leading to a diminished volume of cavernosal smooth muscle and consequential corporoveno-occlusive dysfunction. Current studies support the contention that corporoveno-occlusive dysfunction is an effect rather than the cause of erectile dysfunction. Surgical interventions have consisted primarily of penile revascularization surgery for arterial insufficiency and penile venous surgery for corporoveno-occlusive dysfunction, whatever the mechanism. However, the surgical effectiveness remained debatable and unproven, mostly owing to the lack of consistent hemodynamic assessment, standardized select patient and validated outcome measures, as well as various surgical procedures. Penile vascular surgery has been disclaimed to be the treatment of choice based on the currently available guidelines. However, reports on penile revascularization surgery support its utility in treating arterial insufficiency in otherwise healthy patients aged <55 years with erectile dysfunction of late attributable to arterial occlusive disease. Furthermore, it is noteworthy that penile venous surgery might be beneficial for selected patients with corporoveno-occlusive dysfunction, especially with a better understanding of the innovated venous anatomy of the penis. Penile vascular surgery might remain a viable alternative for the treatment of erectile dysfunction, and could have found its niche in the possibility of obtaining spontaneous, unaided and natural erection.

Vacuum therapy prevents corporeal veno-occlusive dysfunction and penile shrinkage in a cavernosal nerve injured rat model.

Erectile dysfunction and penile shrinkage are the common complications after radical prostatectomy. Penile rehabilitation is widely applied after the surgery. Vacuum therapy is one of the three penile rehabilitation methods used in the clinical setting, but its mechanism is not well known. This study was designed to investigate whether vacuum erectile device (VED) can prevent corporeal veno-occlusive dysfunction and penile shrinkage in the bilateral cavernous nerve crush (BCNC) rat model. Adult male Sprague-Dawley rats were randomly assigned into three groups: sham group, BCNC group, and BCNC + VED group. After 4 weeks, penile length and intracavernosal pressure (ICP) were measured, and then the middle part of the penis was harvested after dynamic infusion cavernosometry to complete the following items: smooth muscle/collagen ratios and collagen I/III ratios; ultramicrostructure of the tunica albuginea, endothelial cell, and smooth muscle cell; and the expression of calponin-1 and osteopontin. The penile shortening, peak ICP and ICP drop rate after alprostadil injection were significantly improved with vacuum therapy after 4-week treatment. Compared with BCNC group, VED significantly increased smooth muscle/collagen ratios, decreased collagen I/III ratios, and preserved the ultramicrostructure of the tunica albuginea, endothelial cell, and smooth muscle cell. The data also showed that animals exposed to VED could partially reverse the expression of calponin-1 and osteopontin induced by BCNC. In conclusion, vacuum therapy is effective to prevent penile shrinkage and veno-occlusive dysfunction in penile rehabilitation, which may be associated with well-preserved structure and function of the tunica albuginea, endothelial cell, and smooth muscle cell.

The Effect of Testosterone Replacement Therapy on Penile Hemodynamics in Hypogonadal Men With Erectile Dysfunction, Having Veno-Occlusive Dysfunction.

Hypogonadism may cause veno-occlusive dysfunction (VOD) by structural and biochemical alterations in the cavernosal tissue. The aim of the study was to investigate the effect of testosterone replacement therapy (TRT) on penile hemodynamics in hypogonadal men with erectile dysfunction and VOD. The study included 32 hypogonadal men with erectile dysfunction, having VOD. All patients underwent penile color Doppler ultrasonography (PCDU) at the beginning and 6 months after the initial evaluation. Erectile function was evaluated with the 5-item version of the International Index of Erectile Function (IIEF-5); hypogonadism was evaluated by testosterone measurement and the Aging Male Symptoms (AMS) scale. All patients received transdermal testosterone 50 mg/day for 6 months. Clinical and radiological findings were compared before and 6 months after the TRT. The mean age was 58.81 ± 4.56 (52-69) years. Mean total testosterone levels were 181.06 ± 39.84 ng/dL and 509.00 ± 105.57 ng/dL before and after the therapy, respectively ( p < .001). While all patients had physiological serum testosterone levels (>320 ng/dL) after the therapy, three cases (9.3%) had no clinical improvement of hypogonadism symptoms. Cavernosal artery peak systolic velocity (PSV) and resistive index (RI) significantly increased, and end diastolic velocity (EDV) significantly decreased after TRT. VOD no longer existed in 21 (65.6%) of the cases. This study demonstrated that TRT may restore penile hemodynamics in hypogonadal men with VOD.

Losartan Preserves Erectile Function by Suppression of Apoptosis and Fibrosis of Corpus Cavernosum and Corporal Veno-Occlusive Dysfunction in Diabetic Rats.

BACKGROUND/AIMS: Transforming growth factor-ß1 (TGF-ß1) plays important roles in penile corporal fibrosis and veno-occlusive dysfunction (CVOD). Angiotensin II (Ang II) is critically involved in erectile dysfunction, and blocking of Ang II is more important than inhibition of TGF-ß in non-penile tissue fibrosis. However, the role of Ang II in corporal fbrosis and CVOD in a diabetic condition has not been investigated. METHODS: Diabetic rats were treated with sildenafil or losartan (an Ang II antagonist) alone or in combination. Intracavernosal pressure, dynamic infusion cavernosometry, and histological and molecular alterations of the corpus cavernosum were examined. RESULTS: Diabetic rats exhibited decreases in erectile response, severe CVOD, apoptosis, fibrosis, and activation of the TGF-ß1 pathway. Treatment with sildenafil had a modest effect on erectile response and an insignificant suppressive effect on CVOD, apoptosis, fibrosis, and the TGF-ß1 pathway. Although losartan greatly improved the histological and molecular changes and CVOD as compared with sildenafil, its effect on erectile response was low. The combination of sildenafil and losartan had superior effects on these parameters than did either compound alone. CONCLUSION: Ang II activation may be involved in apoptosis and fibrosis of the corpus cavernosum through Smad and non-Smad pathways, resulting in CVOD and ED. The low efficacy of sildenafil in a diabetic ED rat model was at least partly due to its inadequate effects on apoptosis, fibrosis, and CVOD.

External Mechanical Devices and Vascular Surgery for Erectile Dysfunction.

INTRODUCTION: The field of sexual medicine is continuously advancing, with novel outcomes reported on a regular basis. Given the rapid evolution, updated guidelines are essential to inform practicing clinicians on best practices. AIM: To summarize the current literature and provide clinical guidelines on penile traction therapy, vacuum erection devices, and penile revascularization. METHODS: A consensus panel was held with leading sexual medicine experts during the 2015 International Consultation on Sexual Medicine (ICSM). Relevant literature was reviewed and graded based on Oxford criteria to develop evidence-based guideline and consensus statements. MAIN OUTCOME MEASURES: The development of clinically relevant guidelines. RESULTS: Penile traction therapy is a viable therapy to modestly improve penile length as a primary therapy, before penile prosthesis placement in men with decreased penile length or after surgery for Peyronie's disease. It also might have a role in the acute phase of Peyronie's disease but has inconsistent outcomes in the long-term phase. Vacuum erection devices are effective in creating an erection satisfactory for intercourse, even in difficult-to-treat populations. They also might be used in the post-prostatectomy setting to maintain penile length but have insufficient evidence as a penile rehabilitation therapy. For vasculogenic erectile dysfunction, men with suspected arterial insufficiency can be evaluated with penile Duplex Doppler ultrasonography and confirmatory angiography. Penile revascularization procedures have consistently demonstrated benefits in very select patient populations; however, inadequate data exists to suggest the superiority of one technique. Men with vascular risk factors are likely poor candidates for penile revascularization, although veno-occlusive dysfunction and age are less significant. Therapies for treating primary veno-occlusive dysfunction are not recommended and should be reserved for clinical trials. CONCLUSIONS: Since the prior ICSM meeting, multiple developments have occurred in external mechanical devices and penile revascularization for the treatment of erectile and sexual dysfunction. Sexual medicine clinicians are encouraged to review and incorporate recommendations as applicable to their scope of practice.

Implanted Muscle-Derived Stem Cells Ameliorate Erectile Dysfunction in a Rat Model of Type 2 Diabetes, but Their Repair Capacity Is Impaired by Their Prior Exposure to the Diabetic Milieu.

INTRODUCTION: Muscle-derived stem cells (MDSCs) and other SCs implanted into the penile corpora cavernosa ameliorate erectile dysfunction in type 1 diabetic rat models by replenishing lost corporal smooth muscle cells (SMCs) and decreasing fibrosis. However, there are no conclusive data from models of type 2 diabetes (T2D) and obesity. AIM: To determine whether MDSCs from obese Zucker (OZ) rats with T2D at an early stage of diabetes (early diabetic SCs isolated and cultured in low-glucose medium [ED-SCs]) counteract corporal veno-occlusive dysfunction and corporal SMC loss or lipo-fibrosis when implanted in OZ rats at a late stage of diabetes and whether MDSCs from these OZ rats with late diabetes (late diabetic SCs isolated and cultured in high-glucose medium [LD-SC]) differ from ED-SCs in gene transcriptional phenotype and repair capacity. METHODS: ED-SCs and LD-SCs were compared by DNA microarray assays, and ED-SCs were incubated in vitro under high-glucose conditions (ED-HG-SC). These three MDSC types were injected into the corpora cavernosa of OZ rats with late diabetes (OZ/ED, OZ/LD, and OZ/ED-HG rats, respectively). Untreated OZ and non-diabetic lean Zucker rats functioned as controls. Two months later, rats were subjected to cavernosometry and the penile shaft and corporal tissues were subjected to histopathology and DNA microarray assays. MAIN OUTCOME MEASURES: In vivo erectile dysfunction assessment by Dynamic Infusion Cavernosometry followed by histopathology marker analysis of the penile tissues. RESULTS: Implanted ED-SCs and ED-HG-SCs improved corporal veno-occlusive dysfunction, counteracted corporal decreases in the ratio of SMCs to collagen and fat infiltration in rats with long-term T2D, and upregulated neuronal and endothelial nitric oxide. LD-SCs acquired an inflammatory, pro-fibrotic, oxidative, and dyslipidemic transcriptional phenotype and failed to repair the corporal tissue. CONCLUSION: MDSCs from pre-diabetic rats injected into the corpora cavernosa of rats with long-term T2D improve corporal veno-occlusive dysfunction and the underlying histopathology. In contrast, MDSCs from rats with long-term uncontrolled T2D are imprinted by the hyperglycemic and dyslipidemic milieu with a noxious phenotype associated with an impaired tissue repair capacity. SCs affected by diabetes could lack tissue repair efficacy as autografts and should be reprogrammed in vitro or substituted by SCs from allogenic non-diabetic sources.

Treatment with a combination of ginger, L-citrulline, muira puama and Paullinia cupana can reverse the progression of corporal smooth muscle loss, fibrosis and veno-occlusive dysfunction in the aging rat.

AIMS: Aging associated erectile dysfunction is characterized within the corpora by a progressive apoptosis of the smooth muscle cells and their replacement by collagen. Nitric oxide from iNOS has been shown to inhibit these histological changes in the corpora while PDE5 inhibitors as well as certain nutraceuticals such as ginger, paullinia cupana, muira puama and L-citrulline are known to enhance the effects of NO. We evaluated whether the daily oral administration for 2 months with a combination of ginger, paullinia cupana, muira puama and L-citrulline (COMP-4) can effectively delay the ongoing corporal fibrosis, smooth muscle cell apoptosis and cavernosal veno-occlusive dysfunction (CVOD) seen in middle aged rats similar to that seen with tadalafil. METHODS: 10 Month old Fisher 344 rats were treated or not for two months with COMP-4, tadalafil or a combination of tadalafil plus COMP-4. CVOD was determined by dynamic infusion cavernosometry. Penile sections of the corpora cavernosa were subjected to Masson trichrome staining to evaluate fibrosis and immunohistochemistry for desmin as a marker of smooth muscle content and inducible nitric oxide synthase (iNOS) followed by image analysis. Oxidative stress levels were determined by GSH/GSSG ratio in whole blood. RESULTS: a decline in the non-treated rat's erectile function is evident by 10-12 months of age and is accompanied by a decrease in the corporal smooth muscle content determined by desmin expression and an increase in corporal fibrosis. The daily treatment for two months with COMP-4 reverses this process by reducing systemic oxidative stress and increasing desmin and iNOS expression, similar to that seen with tadalafil or the combination of COMP-4 plus tadalafil. CONCLUSION: An oral combination of ginger, muira puama, Paullinia cupana and L-citrulline seems to be as effective as daily PDE5 inhibitor therapy in either delaying or reversing the onset of the histological and functional characteristics of aging related erectile dysfunction.

Failure to attain stretched penile length after intracavernosal injection of a vasodilator agent is predictive of veno-occlusive dysfunction on penile duplex Doppler ultrasonography.

Penile duplex Doppler ultrasound (PDDU) assesses the etiology of erectile dysfunction. Peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistive index (RI) are common PDDU parameters. We assessed whether stretched penile length (SPL) in the flaccid state and measured penile length at peak erection after intracavernosal injection (ICI) of a vasodilator during PDDU correlated with the etiology of erectile dysfunction. We performed a retrospective review of 93 patients who underwent PDDU for erectile dysfunction. Normal and stretched penile length were measured, both at a flaccid state prior to ICI and at peak erection during PDDU. Collected data included patient demographics, vascular, and anatomic parameters. The mean age was 52 years. SPL was equivalent to peak penile length after ICI in 60 patients (65%, group 1) and did not match in 33 (35%, group 2). There were no significant differences between the two groups in terms of flaccid, stretched, and post-ICI erect penile lengths, IIEF score, PSV, percent rigidity or tumescence, and vasodilator dose used. Patients in group 2 had less of a change in penile length from flaccid to erect state (36% vs. 44%, p = 0.02), higher EDV (12.0 vs. 8.5, p = 0.041), lower RI (0.6 vs. 1.0, p = 0.046), and more veno-occlusive dysfunction (82% vs. 53%, p = 0.001). On multivariate analysis, failure to reach maximum SPL at peak ICI erection (OR 2.255, CI 1.191-4.271, p = 0.0126), EDV (OR 1.281, CI 1.115-1.471, p < 0.001) and RI (OR 0.694, CI 0.573-0.723, p = 0.009) predicted veno-occlusive dysfunction. Failure to reach maximal SPL during PDDU using ICI with a vasodilator agent predicted veno-occlusive dysfunction, which is independent of both penile rigidity and tumescence. This measurement could serve as another diagnostic tool for predicting veno-occlusive dysfunction when PDDU is not readily available. Limitations include the subjective nature of penile measurements and different PGE1 doses used.

P144, A TGF-ß1 antagonist peptide, synergizes with sildenafil and enhances erectile response via amelioration of cavernosal fibrosis in diabetic rats.

INTRODUCTION: Patients with diabetes exhibit more severe erectile dysfunction (ED) and are less responsive to first-line oral phosphodiesterase type 5 inhibitor (PDE5i). It has been suggested that increased collagen deposition and reduced smooth muscle content in the corpus cavernosum are important mechanisms for diabetes-associated ED and that transforming growth factor-ß1 (TGF-ß1) is a potent fibrotic factor responsible for the structural alterations in the corpus cavernosum. AIMS: The aims of this study are to determine whether activation of TGF-ß1 and its downstream pathways is responsible for the reduced efficacy of the PDE5is in diabetic ED via abnormalities in cavernosal structures and to investigate the synergistic effects of the TGF-ß1 antagonist P144 and sildenafil on erectile response. METHODS: Six weeks after inducting diabetes with streptozotocin in male Sprague-Dawley rats, age-matched control and diabetic rats were treated with vehicle, sildenafil, or P144 alone or in combination for 4 weeks, respectively. MAIN OUTCOME MEASURES: Intracavernous pressure, dynamic infusion cavernosometry, and histological and molecular alterations of the corpus cavernosum were analyzed. RESULTS: Diabetic rats exhibited a decreased erectile response, severe corporal veno-occlusive dysfunction (CVOD), and structural alterations including cavernosal fibrosis and decreased smooth muscle content. Expression and activation of TGF-ß1 and its downstream Smad and non-Smad pathways increased in diabetic rats. Treatment with sildenafil showed modest effect on erectile response and a less suppressive effect on CVOD, cavernosal fibrosis, and molecular alterations. Treatment with P144 had lower effect on erectile response, even greatly improved the histological and molecular alterations and CVOD than sildenafil. The combined treatment with P144 and sildenafil effectively restored erectile response, CVOD, and histological and molecular alterations. CONCLUSION: An insufficient suppressive effect of sildenafil on cavernosal fibrosis, severe CVOD, and TGF-ß1 pathways was implicated in reduced efficacy of the PDE5i in diabetic ED. Treatment with P144 synergized sildenafil and significantly increased erectile response by the potential antifibrotic activity.

Chronic high dose intraperitoneal bisphenol A (BPA) induces substantial histological and gene expression alterations in rat penile tissue without impairing erectile function.

INTRODUCTION: Bisphenol A (BPA), released from plastics and dental sealants, is a suspected endocrine disruptor and reproductive toxicant. In occupationally exposed workers, BPA has been associated with erectile dysfunction (ED). AIMS: To determine whether long-term exposure to high doses of BPA in the rat affects serum levels of testosterone (T) and estradiol (E2), and induces corporal histopathology and resultant ED. METHODS: Young rats were injected intraperitoneal (IP) injection daily with BPA at 25 mg/kg/day or vehicle (n = 8/group). Erectile function was measured at 3 months by cavernosometry and electrical field stimulation (EFS). BPA was assayed in serum, urine, and penile tissue, and serum T and E2 were determined. Quantitative Masson trichrome, terminal deoxynucleotidyl transferase dUTP nick end labeling, Oil Red O, immunohistochemistry for calponin, α-smooth muscle actin, and Oct 4 were applied to penile tissue sections. Protein markers were assessed by Western blots and 2-D minigels, and RNA by DNA microarrays. MAIN OUTCOME MEASURES: Erectile function, histological, and biochemical markers in corporal tissue. RESULTS: In the BPA-treated rats, total and free BPA levels were increased in the serum, urine, and penile tissue while serum T and E2 levels were reduced. In addition, the corpora cavernosa demonstrated a reduction in smooth muscle (SM) content, SM/collagen ratio, together with an increase in myofibroblasts, fat deposits, and apoptosis, but no significant change in collagen content or stem cells (nuclear/perinuclear Oct 4). In the penile shaft, BPA induced a downregulation of Nanog (stem cells), neuronal nitric oxide synthase (nitrergic terminals), and vascular endothelial growth factor (angiogenesis), with genes related to SM tone and cytoskeleton upregulated 5- to 50-fold, accompanied by changes in the multiple protein profile. However, both cavernosometry and EFS were unaltered by BPA. CONCLUSIONS: While rats treated chronically with a high IP dose of BPA developed hypogonadism and a corporal histo- and molecular-pathology usually associated with ED, no changes were detected in erectile function as measured by EFS and cavernosometry. Further studies using alternate routes of BPA administration with various doses and length of exposure are needed to expand these findings.

Outcomes of intralesional interferon-α2B for the treatment of Peyronie disease.

PURPOSE: We evaluated the efficacy of intralesional interferon-α2b for Peyronie disease, reviewed the impact of the timing of therapy from disease onset and identified variables predictive of a response. MATERIALS AND METHODS: We retrospectively reviewed the charts of patients treated with intralesional interferon-α2b from 2001 to 2012. Demographic information, disease characteristics, pretreatment and posttreatment penile duplex ultrasound findings, and objective measures were analyzed. Response was defined as a 20% or greater improvement in curvature. Statistical analysis was done to identify significant changes in variables and identify predictive factors. RESULTS: A total of 127 patients with a mean age of 55 years (range 25 to 76) and a mean±SD pretreatment curvature of 42.4±18.6 degrees underwent a median of 12 biweekly interferon-α2b injections (range 6 to 24). The median history of Peyronie disease was 2.0 years (range 0.5 to 23). Of the patients 54% responded to therapy with an overall mean improvement of 9.0 degrees (p<0.001). Patients with less than 30-degree curvature were most likely to experience a 20% or greater improvement with interferon-α2b (86% response, p<0.001). However, similar overall improvement in pretreatment curvature was noted in all cases. No statistically significant improvement was observed in penile vascular status or ultrasound parameters. The duration of Peyronie disease did not impact the change in curvature. Age, pretreatment curvature, vascular status, penile ultrasound findings, curvature site and International Index of Erectile Function (IIEF) score did not predict the response to therapy. CONCLUSIONS: Intralesional therapy with interferon-α2b resulted in significantly improved curvature without impacting penile vascular parameters. The absolute improvement in curvature was independent of pretreatment curvature or Peyronie disease duration.

Penile vascular surgery for treating erectile dysfunction: Current role and future direction.

Penile vascular surgery for treating erectile dysfunction (ED) is still regarded cautiously. Thus we reviewed relevant publications from the last decade, summarising evidence-based reports consistent with the pessimistic consensus and, by contrast, the optimistically viable options for vascular reconstruction for ED published after 2003. Recent studies support a revised model of the tunica albuginea of the corpora cavernosa as a bi-layered structure with a 360° complete inner circular layer and a 300° incomplete outer longitudinal coat. Additional studies show a more sophisticated venous drainage system than previously understood, and most significantly, that the emissary veins can be easily occluded by the shearing action elicited by the inner and outer layers of the tunica albuginea. Pascal's law has been shown to be a significant, if not the major, factor in erectile mechanics, with recent haemodynamic studies on fresh and defrosted human cadavers showing rigid erections despite the lack of endothelial activity. Reports on revascularisation surgery support its utility in treating arterial trauma in young males, and with localised arterial occlusive disease in the older man. Penile venous stripping surgery has been shown to be beneficial in correcting veno-occlusive dysfunction, with outstanding results. The traditional complications of irreversible penile numbness and deformity have been virtually eliminated, with the venous ligation technique superseding venous cautery. Penile vascular reconstructive surgery is viable if, and only if, the surgical handling is appropriate using a sound method. It should be a promising option in the near future.

Reconstructive surgery for idealising penile shape and restoring erectile function in patients with penile dysmorphology and erectile dysfunction.

OBJECTIVE: To report an innovative combination of two surgical procedures to treat patients with erectile dysfunction and penile deviation, arising from advances in penile anatomy. PATIENTS AND METHODS: From October 1998 to October 2011, 132 men (aged 23-39 years) underwent penile venous stripping and corporoplasty. Of these, 37 were allocated to a transverse and 95 to a longitudinal group, with an infrapubic transverse or pubic median longitudinal approach, respectively. The abridged five-item version of the International Index of Erectile Function (IIEF-5) and cavernosography were used for assessment, as necessary. Under acupuncture-aided local anaesthesia, and after a circumferential incision, the deep dorsal vein and cavernous veins were completely stripped, with 6-0 Nylon sutures for ligation, followed by tunical surgery for correcting the penile shape. RESULTS: In the transverse and longitudinal groups the mean (SD) duration of surgery was 4.6 (0.2) and 4.8 (0.3) h, respectively. Before surgery the mean (SD) IIEF-5 score was 9.4 (2.3) and 9.6 (2.1), which increased to 20.6 (2.4) and 20.8 (2.7), respectively, after surgery. The penile shape (<15°) was deemed satisfactory in 92% (34/37) and 96% (91/95) of patients in the transverse and longitudinal groups, respectively. The cavernosograms consistently showed a good penile shape. There were significant differences in the mean (SD) duration of penile oedema, at 3.2 (1.6) vs. 11.9 (2.1) days, the overall satisfaction rate and the prevalence of hypertrophied scarring (all P < 0.001). CONCLUSION: This combination of unique penile venous stripping with a pubic median longitudinal approach and an anatomy-based corporoplasty is ideally suited to the simultaneous restoration of penile erectile function and morphological reconstruction.

Reversion of penile fibrosis: Current information and a new horizon.

Ageing has a detrimental effect on cavernous tissue and the tunica albuginea of the penis. Furthermore, atherosclerosis of the penile vessels that occurs with ageing causes a decrease in penile oxygen tension. A reduction in smooth muscle cells (SMCs) was shown in relation to diminution of oxygen tension. Chronic ischaemia is therefore not only associated with fibrosis but also with nitric oxide-cyclic guanosine monophosphate reduction. The sensitivity of the α-adrenoceptors on the SMCs increases with ageing. The decrease in penile elasticity and compliance are explained by the changes in the ratio of penile collagen that occur with ageing. Contradictory to the view that testosterone is only necessary for sexual desire, numerous recent studies showed that androgen deprivation produces penile tissue atrophy, alterations in dorsal nerve structure, alterations in endothelial morphology, reduction in trabecular SM content, increase in deposition of extracellular matrix and accumulation of fat-containing cells (adipocytes) in the subtunical region of corpus cavernosum. The aim of the current review is to shed some light on the underlying aetiology of corporal fibrosis especially ageing, cavernous nerve damage, androgen deprivation and tunical fibrosis. Ultimately I will address the proposed prevention of erectile dysfunction associated with penile fibrosis.

Combined intracavernous vasoactive drugs and sildenafil citrate in treatment of severe erectile dysfunction not responding to on-demand monotherapy.

OBJECTIVE: To investigate the effect of chronic use of sildenafil and intracavernous injection (ICI) with trimix in men not responding to on-demand monotherapy with sildenafil or ICI with prostaglandin-E1 (PGE1). PATIENTS AND METHODS: The study included 40 patients with erectile dysfunction (ED), with a mean (SD) age of 50.7 (11.3) years and unresponsive to on-demand sildenafil or ICI with PGE1 as monotherapy. They were assessed using the Sexual Health in Men (SHIM)-5 score for ED severity, penile colour Doppler ultrasonography (CDUS) for peak systolic velocity (PSV), end-diastolic velocity (EDV) and resistance index (RI) with an ICI test using 0.25 mL of trimix of papaverine, PGE1 and phentolamine. Testosterone, prolactin and cholesterol levels were assessed. Patients received 25 mg sildenafil daily for 8 weeks, combined with twice weekly ICI with 0.25 mL of trimix. After treatment, the Erection Hardness Score (EHS), penile CDUS with ICI and ED Inventory of Treatment Satisfaction were assessed. RESULTS: The mean (SD) SHIM-5 score before treatment was 8.3 (0.5) in 15 of the 40 men and 6.3 (0.4) in 25. Penile haemodynamics were normal in five (13%), showed arterial insufficiency in five (13%), venous occlusive disease in 26 (65%) and mixed vascular in four (10%). There was an improved SHIM-5 score in 28 (70%) patients, as shown by their haemodynamic values, duration of erection and EHS with therapy, and 66% satisfaction with treatment. Adverse effects (penile pain, headache, facial flushing, dyspepsia, nasal congestion, dizziness) were reported in 17 patients (43%). CONCLUSION: Chronic use of trimix plus daily low-dose sildenafil improved penile haemodynamics in these patients with ED not responding to on-demand phosphodiesterase-5 inhibitors or ICI with PGE1 monotherapy.