Corporal Veno-occlusive Dysfunction Research Articles

Penile implants in Japan

ABSTRACT Introduction In Japan, APSSM's founding president Shirai developed a silicon single rod that is inserted into the outside corpora in 1971. In the 1990s penile prostheses started to be sold in Japan. However, sales stopped in 2007. Since then, it has been up to doctors to order them individually. Objective we performed 141penile prothesis surgeries between 1992 and 2019.9. Age is 25-81 years average 62 ± 8 years old. the causes of ED are Diabetes 57 cases, arteriosclerosis (hypertension) 24 cases, failure of prosthesis surgery 17 cases, intrapelvic surgery (prostate ca, bladder Ca, rectal Ca) 16 cases, brain disease (bleeding, infarction, Parkinson, meningitis) 12 cases, Renal failure 7 cases, Peyronie ’s disease 5 cases, priapism 2 cases, wrong masturbation habit 1 case. Diabetes was the most common cause. Diagnosis is vasculogenic and neurogenic 88 cases, vasculogenic 54 cases, vasculogenic and curvature 3 cases, neurogenic 6 cases. Methods Anesthesia method is local anesthesia (penile block) 128 cases, general anesthesia 13 cases. Penile prostheses were AMS 700CXM 6 cases, Titan OTR narrow base (Coloplast) 2 case, hydroflex 1 case, AMS Dura II 26 cases, AMS 600 17 cases, Genesis (Coloplast) 84 cases, Koken (Japan) 5 cases. We have used AMS since 1992, The sale of penile protheses in Japan was halted in 2007. Since 2008, Our University doctors have been ordering Coloplast prostheses Implanted penile prosthesis size is 11-19.5cm length average 15.9cm, median 16cm. The diameter is Dura II 1cm (26 cases), AMS 600 0.95cm (15 cases) 1.15cm (2 cases), Genesis 1.1cm (28 cases), Genesis 0.95cm (56 cases). Day surgeries are popular therefore 94% of patients prefer a non-inflatable prosthesis. We devised a single-implant procedure and performed surgery for the following indications:1. Narrow cavernosum because of congenital abnomarity or re-operations. 2. Small penis. 3. Uncontrolled diabetes. 4. ED caused by corporal veno-occlusive dysfunction (CVOD) in a young man. 5. Patient preference for a warm erect penis (with a PDE5 inhibitor). Single implant surgery has a high satisfaction rate of 98% with no complications, but there are still many enlargement operations and use of PDE5 inhibitors. Results Intercourse was possible 137 cases (97.0%) and impossible 4 cases (3.0%). Ejaculation was possible 100cases (77%), impossible 32 cases (24%) (prostate or rectal surgery, retrograde ejaculation due to DM). Complication rate is 7.8%, exposure of one side prosthesis to urethra 2.8%, exposure of one side prosthesis to skin 0.7%, Exposure of tube (AMS700CXM) 0.7%, persistent pain 2.1%, infection 1.4%. Satisfaction rate is 95.0% Conclusions The penile prosthesis is still considered to be the surgical gold standard for treatment of ED. All other available treatments for ED should be compared with the results of penile prosthesis surgery. In Japan, 95% of day surgeries use non-inflatable prostheses. Disclosure Work supported by industry: no.

Metabolic Syndrome and Erectile Dysfunction

Metabolic syndrome (MetS) is considered a risk factor for erectile dysfunction (ED), and ED is almost three times more prevalent in men with MetS. Vascular pathologies are a significant factor for the development of ED, and many experts suggest endothelial dysfunction (EnD) as a likely explanation for the association between ED and MetS. Studies also show that corporal vascular and trabecular smooth muscle dysfunction leads ultimately to corporal veno-occlusive dysfunction. Different functional system abnormalities, such as nervous degenerations, hormonal insufficiencies, and metabolic factors (e.g., hyperlipidemia, advanced glycation end products), are also likely involved in the pathophysiological pathways. Autonomic neuropathy is also commonly encountered in patients and animal models of MetS. From another perspective, low testosterone levels may be predictive of MetS. Several studies concluded that components of MetS, such as high blood pressure, obesity, hyperinsulinemia, T2DM, hyperglycemia, hypertriglyceridemia, elevated C-Reactive protein, and low HDL levels, were all associated with decreased serum testosterone levels. Lifestyle modification, such as exercise and diet, are the first-line treatment for MetS. Studies have found that a 10% weight loss has been shown to significantly increase IIEF-5 scores. Exercise was also shown to increase endothelial-derived NO and decrease oxidative stress, resulting in a lower risk of developing ED in physically active men. Metformin combined with PDE5 inhibitors is a promising treatment approach, although with limited research.

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.

Current diagnosis and management of erectile dysfunction.

Erectile dysfunction (ED) is a common male sexual dysfunction associated with a reduced quality of life for patients and their partners. ED is associated with increasing age, depression, obesity, lack of exercise, diabetes mellitus, hypertension, dyslipidaemia, cardiovascular disease and lower urinary tract symptoms related to benign prostatic hyperplasia. The evaluation of men with ED requires a full medical and personally and culturally sensitive sexual history, a focused clinical examination, fasting glucose levels, a fasting lipid profile and, in select cases, a total testosterone level and a prostate-specific antigen test. Treatment of ED requires lifestyle modification, reduction of comorbid vascular risk factors, and treatment of organic or psychosexual dysfunction with either pharmacotherapy alone or in combination with psychosexual therapy. Between 60% and 65% of men with ED, including those with hypertension, diabetes mellitus, spinal cord injury and other comorbid medical conditions, can successfully complete intercourse in response to the phosphodiesterase type 5 inhibitors (PDE5i) sildenafil, tadalafil, vardenafil and avanafil. Patient-administered intracorporal injection therapy using vasodilator drugs such as alprostadil is an effective treatment and is useful in men who fail to respond to oral pharmacological agents. Surgical treatment of ED with multicomponent inflatable penile implants is associated with high satisfaction rates. Penile arterial revascularisation and venous ligation surgery are associated with relatively poor outcome results in men with penile atherosclerotic disease or corporal veno-occlusive dysfunction.

ERECTILE DYSFUNCTION AND CAVERNOUS VENO-OCCLUSIVE DISEASE

GoalTo provide a state-of-the-art literature review on veno-occlusive diseases as a pathomechanism of vasculogenic erectile dysfunction (ED).MethodsA comprehensive systematic literature search was conducted followed by sorting, review, and summarizing.
 ResultsThe systematic review of the literature reveals a significant number of recent studies dealing with new minimally invasive methods to provide a potential solution of caverno-venous leakage. Even the long-term results reported demonstrate considerable improvement of ED caused by this condition. Furthermore, 3-D computed tomography cavernosography (CT-cavernosography) is a new technology, which can provide high-resolution images of venous drainage from any angle and shows to be very helpful for both the diagnosis of corporal veno-occlusive dysfunction and the anatomical study of the human penile venous system. The application of this technology may also lead to better strategies in venous leak treatment. Over 30 published studies were found in the literature with good results after caverno-venous leak treatment. Altogether, 13 comparable studies including 538 patients were found, in which a mean short-term success rate of almost 80% and a mean long-term success rate of up to 74% was achieved. None of the studies described major complications.ConclusionED is an increasingly important issue, especially in young men. Whereas the current treatment strategies are mostly focused on older men, young patients are seeking more a longer lasting or more definitive solutions, rather than a lifelong medical treatment. Various chronic disorders have been reported to be associated with elevated rates of ED including depression, diabetes, and cardiovascular and neurological disease in older men. Properly selected cases of young men may benefit from treatment of caverno-venous leak treatment. The current strategy in the treatment of ED in young men may be reconsidered.

The two phases of the clinical validation of preclinical translational mechanistic research on PDE5 inhibitors since Viagra's advent. A personal perspective.

The FDA approval of Viagra (sildenafil) for the on demand treatment of erectile dysfunction (ED) through relaxation of the corporal and cavernosal vascular smooth muscle that results in an increase in blood flow to the corporal tissues stemmed from 2 decades of research, mainly at academic centers. This culminated in the finding of the nitric oxide/cGMP pathway as the mediator of penile erection, followed by some years of basic studies and clinical validation at Pfizer. Further on, new translational laboratory and animal research from our group initiated a second phase when we proposed an alternative therapeutic schedule and mechanism of action for PDE5 inhibitors (PDE5i) in both corporal veno-occlusive dysfunction (CVOD) and Peyronie's disease (PD), specifically, continuous long-term administration (CLTA) to achieve sustained levels of cGMP within the penis. Due to the extended half-life of the long-acting PDE5i, tadalafil, this new alternative encompasses preferentially daily administration, although shorter half-life PDE5i, like sildenafil and vardenafil work too, depending on the duration, dose, and frequency of their administration This novel use was initially supported by showing the antifibrotic/antioxidant effects of nitric oxide and cGMP, produced by the induction of iNOS, as a mechanism of defense against collagen deposition in the localized fibrotic plaque of PD in an avascular tissue, the tunica albuginea. Our studies on iNOS and the progressive diffuse fibrosis occurring in the smooth muscle in CVOD, led to proposing the CLTA of PDE5i for maintaining sustained cGMP levels both in PD and in CVOD in order to halt or regress the penile fibrosis. In CVOD, we showed that PDE5i protect the corporal smooth muscle and reduce myofibroblast activation and number, counteracting the underlying corporal tissue pathology that causes CVOD, and potentially ameliorating long-term CVOD or even curing it. This review is focused on this novel PDE5i anti-fibrotic therapeutic concept.

12 years together. The experience of using Magic Staff Forte for the treatment of erektil dysfunktion ED

A five-year, prolonged-time study of patients with corporal venoocclusive dysfunction, for treatment of which was used by Magic Staff Forte, was performed with a frequency of 2 months twice a year at even intervals. The results show the effectiveness of the treatment schemes presented.

Effect of ginger, Paullinia cupana, muira puama and l- citrulline, singly or in combination, on modulation of the inducible nitric oxide- NO-cGMP pathway in rat penile smooth muscle cells

IntroductionCOMP-4 is a natural compound-based dietary supplement consisting of the combination of ginger, Paullinia cupana, muira puama and l-citrulline, which when given long-term has been shown in the aged rat to a) upregulate iNOS in the penile smooth muscle cells (SMC), b) reverse the corporal SMC apoptosis and fibrosis associated with corporal veno-occlusive dysfunction (CVOD), and c) improve resulting erectile function. To elucidate the mechanism of how COMP-4 and its individual components modulate the iNOS-cGMP pathway, an in vitro study was conducted using a rat corporal primary SMC culture to determine its effect on NOS, soluble guanylate cyclase (sGC), cGMP and the phosphodiesterase 5 enzyme (PDE5). Materials and methodsPrimary SMC cultures using the explant technique were initiated by cutting small pieces of corporal tissue from 8 week old Sprague-Dawley rats. The SMC were grown in Dulbecco media with 20% fetal calf serum. The SMC were then incubated with or without COMP-4 (0.69 mg/ml) or its ingredients alone (ginger: 0.225 mg/ml; muira puama, Paullinia cupana and l-citrulline each at 0.9 mg/ml) for up to 24 h mRNA and protein were extracted and used for the determination of NOS, sGC and PDE5 content. cGMP content was determined by ELISA. L-NIL (4 μM) was used as an inhibitor of iNOS activity. ResultsCompared to the control values, COMP-4 upregulated expression of cGMP by 85%, induced a 42 fold increase in sGC as well as a 15 fold increase in both iNOS protein and mRNA content while it decreased both PDE5 mRNA and protein content each by about 50%. L-NIL completely inhibited the effect of COMP-4 on cGMP production. When compared with each of the individual four components of COMP-4, it appears that COMP-4 itself had the most profound effect in modulating each one the specific steps within the iNOS-cGMP pathway. ConclusionsThis in vitro study demonstrates that COMP-4 is capable of activating the endogenous cellular iNOS-cGMP pathway within the CSM cells, which is theorized to be responsible for reducing the fibrosis and apoptosis as well as the CVOD observed in the aging rat penis. Further studies will be necessary in order to determine whether supplementation of COMP-4 on a daily basis may be beneficial in halting or reversing this aging related erectile dysfunction in the clinical setting.

385 Losartan Preserves Erectile Function by Suppression of Cavernosal Fibrosis and Corporal Veno-Occlusive Dysfunction in Diabetic Rats

385 Losartan Preserves Erectile Function by Suppression of Cavernosal Fibrosis and Corporal Veno-Occlusive Dysfunction in Diabetic Rats

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.

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. 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. ED-SCs and LD-SCs were compared by DNA microarray assays, and ED-SCs were incubated invitro 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. In vivo erectile dysfunction assessment by Dynamic Infusion Cavernosometry followed by histopathology marker analysis of the penile tissues. 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. 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 invitro or substituted by SCs from allogenic non-diabetic sources.

The vascular and neurogenic factors associated with erectile dysfunction in patients after pelvic fractures.

ABSTRACTErectile dysfunction (ED) is a common complication of pelvic fractures. To identify the vascular and neurogenic factors associated with ED, 120 patients admitted with ED after traumatic pelvic fracture between January 2009 and June 2013 were enrolled in this study. All patients answered the International Index of Erectile Function (IIEF-5) questionnaire. Nocturnal penile tumescence (NPT) testing confirmed the occurrence of ED in 96 (80%) patients on whom penile duplex ultrasound and neurophysiological testing were further performed. Of these ED patients 29 (30%) were demonstrated only with vascular abnormality, 41 (42.7%) were detected only with neural abnormality, 26 (27.1%) revealed mixed abnormalities. Of the 55 patients (29+26) with vascular problems, 7 patients (12.7%) with abnormal arterial response to intracavernous injection of Bimix (15mg papaverine and 1mg phentolamine), 31 (56.4%) with corporal veno-occlusive dysfunction and 17 (30.9%) had both problems. Of the 67 (41+26) patients with abnormal neurophysiological outcomes, 51 (76.1%) with abnormal bulbocavernosus reflex (BCR), 20 (29.9%) with pathological pudendal nerve evoked potentials (PDEPs) and 25 (37.3%) with abnormal posterior tibial somatosensory nerve evoked potentials (PTSSEPs). Our observation indicated that neurogenic factors are important for the generation of ED in patients with pelvic fracture; venous impotence is more common than arteriogenic ED.

Surgical Treatment of Erectile Dysfunction.

Currently, oral pharmacotherapy is the dominant treatment for erectile dysfunction. The aim of this article is to give an up-to-date summary of the possibilities of surgical therapy. A search of the literature over the last decade was performed. Relevant papers and guidelines on the topic were reviewed and included. We evaluate therapy options, such as penile vein surgery, arterial revascularization, and penile prosthetics. Vein surgery has faded into total insignificance due to the efficiency of oral and intracavernous therapeutics, and because of the known pathophysiology of corporal veno-occlusive dysfunction and the disappointing long-term results published in the literature. Penile revascularization surgery is performed today only in very limited number of patients with strict selection criteria such as age and exclusion of vascular risk factors. Penile prosthetics is the only surgical therapy option maintaining its significance as a cure for erectile dysfunction. There are convincing long-term results with a high degree of patient and partner satisfaction, high patient acceptance, and a good functional durability of the mostly three-piece inflatable devices. Bertero EB and Antunes DL. Surgical treatment of erectile dysfunction.

Restoration of Erectile Function by Suppression of Corporal Apoptosis, Fibrosis and Corporal Veno-Occlusive Dysfunction with Rho-Kinase Inhibitors in a Rat Model of Cavernous Nerve Injury

We determined whether Rho-kinase inhibition would improve corporal veno-occlusive dysfunction by suppressing apoptosis and fibrosis via normalization of the Rho-kinase driven pathways related to the 2 structural alterations in a rat model of cavernous nerve crush injury. A total of 30 male 10-week-old male Sprague Dawley® rats were equally divided into 3 groups, including sham surgery, cavernous nerve crush injury and cavernous nerve crush injury treated with fasudil. The treated group received fasudil (30 mg/kg) daily for 4 weeks starting day 1 postoperatively. Electrostimulation and dynamic infusion cavernosometry were performed 4 weeks postoperatively. Penile tissue was processed for imm unohistochemistry, double immunofluorescent and Masson trichrome staining, TUNEL, caspase-3 activity assay and Western blot. The cavernous nerve crush injury group showed significantly lower intracavernous pressure/mean arterial pressure, and higher maintenance and drop rates than the sham surgery group. Rho-kinase inhibition in the injury plus fasudil group restored erectile responses and dynamic infusion cavernosometry parameters. Increased apoptosis, decreased immunohistochemical staining of α-SMA and increased caspase-3 activity were noted in the injury group. In that group densitometry revealed increased ROCK1 expression, increased MYPT1 phosphorylation, decreased Akt phosphorylation, decreased Bad phosphorylation and a decreased Bcl2-to-Bax ratio. A significantly decreased smooth muscle-to-collagen ratio and increased fibroblast pCofilin were also observed in the injury group, as was increased phosphorylation of cofilin, a downstream effector of LIMK2. Rho-kinase inhibition in the injury plus fasudil group alleviated the histological and molecular dysregulation. Our data suggest that early inhibition of Rho-kinase after cavernous nerve crush injury may prevent corporal apoptosis and fibrosis by suppressing the Akt/Bad/Bax/caspase-3 and LIMK2/cofilin pathways, preventing corporal veno-occlusive dysfunction and erectile dysfunction.

Prostate cancer survivorship: a review of erectile dysfunction and penile rehabilitation after prostate cancer therapy.

Prostate cancer diagnosis and treatment adversely affect quality of life for most men. The true incidence of erectile dysfunction (ED) after prostate cancer therapy is unknown, and the rates of ED in radical prostatectomy (RP) and radiation groups are similar, although the onset of ED is often later in patients treated with radiation therapy. Proposed pathophysiological mechanisms of ED include neurovascular injury, local inflammatory changes, damage to nearby supporting structures, cavernosal smooth muscle hypoxia with ensuing smooth muscle apoptosis and fibrosis, and corporal veno-occlusive dysfunction causing venous leakage. Penile rehabilitation aims to help men regain the ability to achieve erections sufficient for satisfactory sexual intercourse during rehabilitation from prostate cancer treatment, and ultimately to return to pretreatment erectile function. While there is no consensus on the ideal rehabilitation regimen, many sexual health experts agree that treatment should start as soon as possible to protect and/or prevent corporal endothelial and smooth muscle damage. Current management strategies for erectile function rehabilitation predominantly relate to patients who have had RP. Phosphodiesterase type 5 inhibitors, intracavernosal injection of vasoactive agents and vacuum erection devices are options which can be used in a rehabilitation program. Penile implants should be considered if patients do not respond to medical therapies. To facilitate informed decision making, patients should be presented with all treatment options, and told that rehabilitation and treatment for ED as early as possible after prostate cancer therapy will result in faster and better recovery of erectile function and preserve sexual continuity.

494 Restoration of erectile function by suppression of corporal apoptosis, fibrosis and corporal veno-occlusive dysfunction with Rho-kinase inhibitor in a rat model of cavernous nerve injury

494 Restoration of erectile function by suppression of corporal apoptosis, fibrosis and corporal veno-occlusive dysfunction with Rho-kinase inhibitor in a rat model of cavernous nerve injury

Importancia de la rehabilitación precoz de los cuerpos cavernosos tras prostatectomía radical

ObjectivesPrimary: to evaluate the importance of early rehabilitation of the corpus cavernosum on erectile function after radical prostatectomy. Secondary: to analyse the factors associated with better response. Material and methodRetrospective study in patients treated with intracavernous injections after radical prostatectomy between 1 January 2006 and 31 December 2008. We included patients lacking a history of erectile dysfunction prior to surgery, not responding to phosphodiesterase-5 inhibitors. All patients underwent colour echo-doppler after injection of prostaglandin E1 10-20mg. The outcomes of these 2 groups were then compared according to how early rehabilitation began after surgery (early, <6 months, or late, >6 months). ResultsThere were 82 patients included in the study. In the multivariate analysis, predictive factors of good response to treatment were: early onset of rehabilitation (OR: 0.06; 95% CI: 0.014-0.26), higher peak systolic velocity during the test (OR: 1.01; 95% CI: 1.01-1.1) and favourable histopathological stage (OR: 0.15; 95% CI 95%: 0.036-0.6). The colour echo-doppler procedure after prostaglandin E1 injection showed abnormal values more frequently in the late-onset than in the early group (89.5% [n=34] vs. 65.9% [n=29]; P=.01). Corporal veno-occlusive dysfunction was presented by 40.2% (n=33) of subjects, with the late-onset group presenting higher values (5.53±1.4cm/sec) than the early group (4.75±1.03cm/sec) (P=.005). The presence of functional erections at 18 months’ follow-up was higher in the early onset group (P<.001). ConclusionsAccording to this study, early erectile dysfunction rehabilitation after radical prostatectomy achieves better results than late rehabilitation in patients.

P144, A TGF-β1 Antagonist Peptide, Synergizes with Sildenafil and Enhances Erectile Response via Amelioration of Cavernosal Fibrosis in Diabetic Rats

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-β1 (TGF-β1) is a potent fibrotic factor responsible for the structural alterations in the corpus cavernosum. The aims of this study are to determine whether activation of TGF-β1 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-β1 antagonist P144 and sildenafil on erectile response. 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. Intracavernous pressure, dynamic infusion cavernosometry, and histological and molecular alterations of the corpus cavernosum were analyzed. 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-β1 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. An insufficient suppressive effect of sildenafil on cavernosal fibrosis, severe CVOD, and TGF-β1 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.

Standard Operating Procedures for Vascular Surgery in Erectile Dysfunction: Revascularization and Venous Procedures

The impact of penile blood supply on erectile function was recognized some 500 years ago. At the turn of the 20th century first results of penile venous ligation were published and in 1973 the first surgical attempts to restore penile arterial inflow were undertaken. Numerous techniques were published in the meantime, but inclusion criteria, patient selection, and success evaluation differed extremely between study groups. To develop evidence-based standard operating procedures (SOPs) for vascular surgery in erectile dysfunction, based on recent state of the art consensus reports and recently published articles in peer-reviewed journals. Based on the recent publication of the consensus process during the 2009 International Consultation on Sexual Medicine in Paris, recommendations are derived for diagnosis and surgical treatment of vascular erectile dysfunction. In addition several recent publications in this field not mentioned in the consensus statements are included in the discussion. The Oxford system of evidence-based review was systematically applied. Due to the generally low level of evidence in this field expert opinions were accepted, if published after a well-defined consensus process in peer-reviewed journals. Referring to penile revascularization it may be concluded, that in the face of missing randomized trials, only recommendations grade D may be given: this kind of surgery may be offered to men less than 55 years, who are nonsmokers, nondiabetic, and demonstrate isolated arterial stenoses in the absence of generalized vascular disease. The evidence level for recommendations concerning penile venous ligations may be even lower. Too many unsolved controversies exist and universal diagnostic criteria for patient selection as well as operative technique selection have not been unequivocally established. This kind of surgery is still considered investigational but may be offered in special situations on an individualized basis in an investigational or research setting after obtaining written consent, using both pre- and postoperatively validated measuring instruments of success evaluation. SOPs for penile revascularization procedures can be developed, concerning a highly selected patient group with isolated arterial stenoses. Based on the available data it is not yet possible to define SOPs for surgical treatment of corporal veno-occlusive dysfunction.

Separate or Combined Treatments with Daily Sildenafil, Molsidomine, or Muscle‐Derived Stem Cells Prevent Erectile Dysfunction in a Rat Model of Cavernosal Nerve Damage

Long-term daily administration of phosphodiesterase type 5 (PDE5) inhibitors in the rat prevents or reverses corporal veno-occlusive dysfunction (CVOD) and smooth muscle cell (CSMC) loss and fibrosis, in both aging and bilateral cavernosal nerve resection (BCNR) models for erectile dysfunction. In the aging rat model, corporal implantation of skeletal muscle-derived stem cells (MDSC) reverses CVOD. Nitric oxide (NO) and cyclic guanosine monophosphate can modulate stem cell lineage. To investigate in the BCNR model the effects of sildenafil at lower doses, alone or in combination with MDSC or the NO donor molsidomine, on CVOD and the underlying corporal histopathology. CVOD, histological, and biochemical markers in rat corporal tissue. Methods. Rats subjected to BCNR were maintained for 45 days either untreated, or received sildenafil in the water or retrolingually at 10, 2.5, and 1.25 mg/kg/day (medium, low, and very low doses), or intraperitoneal molsidomine, or MDSC implantation into the corpora cavernosa separately or in combination. Cavernosometry evaluated CVOD. Histopathology was assessed on penile sections by Masson trichrome, immunohistochemistry for α-smooth muscle actin (ASMA), or immunofluorescence for neuronal nitric oxide synthase (nNOS)/neurofilament 70, and in fresh tissue by Western blot for various markers and picrosirius red for collagen. All treatments normalized erectile function (drop rate), and most increased the CSMC/collagen ratio and ASMA expression in corporal tissue sections, and reduced collagen content in the penile shaft. MDSC also increased nNOS and brain-derived neurotrophic factor. The combination treatment was not superior to MDSC or sildenafil given alone, and upregulated PDE5. Lowering the dose of a continuous long-term sildenafil administration still maintained the prevention of CVOD in the BCNR rat previously observed, but it was less effective on the underlying histopathology. As in the aging rat model, MDSC also counteracted CVOD, but supplementation with very low-dose sildenafil did not improve the outcome.

Three‐dimensional CT cavernosography: reconsidering venous ligation surgery on the basis of the modern technology

• To examine the feasibility of three-dimensional (3D) CT cavernosography in the diagnosis of corporal veno-occlusive dysfunction. • The subjects were 55 patients who had failed to respond to phosphodiesterase type 5 inhibitors. We performed pharmacodynamic infusion cavernosometry and cavernosography, using 60 mg papaverine hydrochloride. • Cavernosography was performed at 90 mmHg intracavernous pressure, using a multi-slice CT scan system. The 3D images were reconstructed using aquarius net station, ver.2 computer software. • For comparison with conventional cavernosography, maximum intensity projection (MIP) images were used. A flow of 20 mL/min or being more capable of maintaining 90 mmHg of intracavernous pressure indicated veno-occlusive dysfunction. • Forty-five of the 55 patients were diagnosed with corporal veno-occlusive dysfunction. 3D-CT cavernosography revealed drainage veins in all 45 cases, including cavernous veins, dorsal veins, crural veins and other emissary veins. • Compared with 3D-CT cavernosography, observing cavernous veins and the proximal part of the deep dorsal veins using MIP imaging was especially difficult because the origins of the penile veins are often behind the pelvic bone or cavernous body. • Of the patients who seemingly had leakage via the deep dorsal vein, 80.6% did not in fact have leakage via this vein, but had other leakages. The image resolution of 3D-CT cavernosography was significantly higher than that of MIP. • 3D-CT cavernosography can provide high-resolution images of venous drainage from any angle. We conclude that the images obtained by 3D-CT cavernosography are very helpful for both the diagnosis of corporal veno-occlusive dysfunction and the anatomical study of the human penile venous system.