Corpus Cavernosum Research Articles

Interaction of Icariin from Epimedium koreanum and Udenafil on the Relaxation of Rabbit Penile Corpus Cavernosum Tissue

Interaction of Icariin from Epimedium koreanum and Udenafil on the Relaxation of Rabbit Penile Corpus Cavernosum Tissue

Effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus (COVID-19) vaccination on male fertility.

Coronavirus disease 2019, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains an ongoing global public health challenge. This disease causes damage not only to the respiratory system, affecting the normal physiological function of the lungs, but also to other vital organs, such as the heart and testicles. Existing studies have shown that co-expression of angiotensin-converting enzyme 2 and transmembrane serine protease 2 is the main mechanism by which SARS-CoV-2 invades host cells. Angiotensin-converting enzyme 2-expressing cells are widespread in the corpus cavernosum, reproductive tract and testis of men, which has raised concerns. Furthermore, abnormal sex hormone levels and decreased semen parameters were observed in coronavirus disease 2019 patients. This study comprehensively assessed the effects of SARS-CoV-2 infection on the testis, semen parameters, sex hormone levels and erectile function, and discussed possible transmission routes during sexual intercourse and the effect of vaccination on male fertility.

ROUX-en-Y gastric bypass surgery improves metabolic syndrome-related erectile dysfunction in mice via the IRS-1/PI3K/AKT/eNOS pathway.

Although many clinical studies have shown that ROUX-en-Y gastric bypass (RYGB) surgery significantly improves metabolic syndrome-related erectile dysfunction (MED), the role and mechanism are unclear. In this study we used a mouse model to explore how RYGB improves MED induced by a high-fat diet (HFD). We established a mouse model of metabolic syndrome by feeding an HFD for 16weeks. The mice were randomly assigned to the standard chow diet (SCD), HFD, or RYGB groups. Body weight, fasting blood glucose, plasma insulin, and total plasma cholesterol were analyzed. Erectile responses were evaluated by determining the mean systolic blood pressure and the intracavernosal pressure (ICP). Penile histologic examination (Masson's trichrome and immunohistochemical stain) and Western blot were performed. Compared with the SCD group, the ICP in the sham group was significantly lower, and the ICP of the RYGB was significantly increased. Masson's trichrome and immunohistochemical staining showed that the content of endothelium and smooth muscle in the corpus cavernosum of mice with MED was significantly reduced. Western blot analysis showed a significant decrease in α-smooth muscle actin and a significant increase in osteopontin in penile tissue in the sham group, which was improved by RYGB surgery. Furthermore, RYGB significantly increased IRS-1/PI3K/Akt/eNOS phosphorylation. In this study we explored the mechanism of bariatric surgery to improve erectile dysfunction associated with metabolic syndrome and provided a theoretical basis for clinical research. First, we did not investigate the mechanism by which RYGB affects the IRS-1/PI3K/Akt/eNOS signaling pathway. Second, the effect of the IRS-1/PI3K/Akt/eNOS signaling pathway on the function of corpus cavernosum endothelial cells and smooth muscle cells remains to be investigated in cellular studies. This study demonstrated that RYGB may not only improve metabolic parameters but also restore erectile function in MED patients. The mechanism of the therapeutic effect of RYGB may be reactivation of the IRS-1/PI3K/Akt/eNOS pathway.

(PM-17) THE ROLE OF PHOSPHODIESTERASE-5 INHIBITORS IN THE TREATMENT OF COMPLEX PENILE WOUNDS: A CASE REPORT AND LITERATURE REVIEW

Abstract Introduction/Objective Phosphodiesterase-5 inhibitors (PDE5i) are traditionally employed for the management of erectile dysfunction and lower urinary tract symptoms. However, their role in the healing of complex penile wounds remains scarcely discussed. This study aims to describe the case of a 27-year-old man who suffered from penile strangulation, treated with sildenafil. Additionally, a literature review concerning the use of PDE5i for the treatment of complex penile injuries will be conducted. Methods A 27-year-old man presented to the emergency room after a self-induced penile strangulation using a ring placed at the base of the penis. Extensive necrosis of the corpus cavernosum was identified through magnetic resonance imaging. Considering the psychosocial implications of penile amputation, organ preservation was chosen, and conservative treatment with sildenafil and daily local dressings was initiated. Thirty days after admission, Doppler ultrasound revealed symmetrical corpus cavernosum with normal echogenicity and usual blood flow patterns. Subsequently, the patient underwent superficial necrotic tissue debridement followed by partial skin grafting in a second stage, leading to hospital discharge after 55 days of hospitalization. Results PDE5 inhibitors enhance nitric oxide bioavailability, promoting vasodilation and improved tissue oxygenation, thereby facilitating various phases of the healing process. Evidence indicates their benefit in microvascular perfusion in skin and soft tissues. Reports suggest satisfactory outcomes of topical PDE5i application in radiation-induced lesions, implying their role in epidermal cell expansion, reduction of inflammatory infiltrates, enhanced vascularization, and decreased collagen deposition. Conclusion This study presents a successful case of sildenafil use in treatment of a complex penile wound, shedding light on an unconventional application of PDE5i. Financing No conflict.

Experimental testing combined with inverse-FE for mechanical characterisation of penile tissues

Erectile dysfunction (ED) predominantly affects men in their 40–70s and can lead to poor quality of life. One option for ED treatment is surgical implantation of an inflatable penile prosthesis (IPP). However, they can be associated with negative outcomes including infection, migration or fibrosis. To improve outcomes, the interaction between the IPP device and surrounding tissues needs further investigation and this could be achieved using pre-clinical testbeds, but they need to be informed by extensive tissue testing.In this study, an experimental approach is adopted to characterise the mechanics of horse penile tissue and establish a testing protocol for penile tissue. The whole penis segments were tested in plate compression tests to obtain whole penis behaviour which is necessary for validation of a pre-clinical testbed, whilst tensile and compression tests were performed on individual penile tissues, namely corpus cavernosa and tunica albuginea. The second part of the paper deals with the development of a computational model employing an inverse finite element approach to estimate the material parameters of each tissue layer. These material parameters are in good agreement with the experimental results obtained from the individual tissue layers and whole organ tissue tests. This paper presents the first study proposing realistic nonlinear elastic material parameters for penile tissues and offers a validated testbed for IPPs. Statement of significanceErectile Dysfunction (ED) affects over half the male population aged 40–70 potentially leading to poor quality of life. Patients not responding to conventional treatments of ED, are advised to use penile prostheses which can create an erection using implanted inflatable cylinders. A significant drawback of such prostheses, however, is the substantial tissue damage they can induce during their usage. Preclinical testbeds, including computational and bench-top models, could offer an efficient means of improving device designs to mitigate this damage but such testbeds require extensive knowledge of penile tissue properties. In this study, the authors determine penile tissue mechanics and apply an inverse FE approach to characterise the penile material properties required to validate preclinical models of the penis.

Cldn4 overexpression promotes penile cavernous smooth muscle cell fibrotic response via the JNK signaling pathway.

Erectile dysfunction (ED), defined as the inability to achieve or maintain a penile erection sufficient to satisfy sexual behavior, is prevalent worldwide. Using previous research, bioinformatics, and experimental confirmation, we aimed to discover genes that contribute to ED through regulating hypoxia in corpus cavernosum smooth muscle cells (CCSMCs). We used the Gene Expression Omnibus to acquire the sequencing data of the corpus cavernosum transcriptome for diabetic ED and nerve injury type ED rats. We intersected the common differentially expressed genes. Further verification was performed using single cell sequencing. Real-time quantitative polymerase chain reaction and immunofluorescence were used to investigate whether the differentially expressed genes are found in the corpus cavernosum. We used induced hypoxia to assess cell viability changes, and we developed a lentivirus overexpressing Cldn4 for in vitro and in vivo experiments to measure changes in JNK signaling, fibrosis, hypoxia, and erectile function. Our results indicate that targeting the JNK pathway and decreasing local hypoxia may be better options for therapeutic intervention to improve erectile function. We identified Cldn4 and found its expression increased in the corpora cavernosa of the 2 datasets. In addition, we found that hypoxia can increase the expression of Cldn4, activate the JNK signaling pathway, and exacerbate fibrosis in CCSMCs. Cldn4 overexpression in CCSMCs activated the JNK signaling pathway and increased fibrotic protein expression. Last, rat corpus cavernosum overexpressing Cldn4 activated the JNK signaling pathway, increased local fibrosis, and impaired erectile function. Through bioinformatics and in vitro and in vivo experiments, we found that Cldn4 has a negative effect on ED, and targeting Cldn4 may provide new ideas for ED treatment. Although we have identified Cldn4 as a potential target for ED treatment, we have only conducted preliminary validation on CCMSCs, and we still need to further validate in other cell lines. CCSMC hypoxia leads to increased Cldn4, in both nerve injury and diabetic ED rat models, and promotes fibrosis by activating the JNK signaling pathway.

PKC Inhibition Improves Human Penile Vascular Function and the NO/cGMP Pathway in Diabetic Erectile Dysfunction: The Role of NADPH Oxidase.

Erectile dysfunction (ED) is a frequent and difficult-to-treat condition in diabetic men. Protein kinase C (PKC) is involved in diabetes-related vascular and cavernosal alterations. We aimed to evaluate the role of PKC in endothelial dysfunction and NO/cGMP impairment associated with diabetic ED in the human corpus cavernosum (CC) and penile resistance arteries (PRAs) and the potential mechanisms involved. Functional responses were determined in the CC and PRAs in patients with non-diabetic ED and diabetic ED undergoing penile prosthesis insertion. PKC activator 12,13-phorbol-dibutyrate (PDBu) impaired endothelial relaxations and cGMP generation in response to acetylcholine in the CC from non-diabetic ED. PDBu also impaired responses to a PDE5 inhibitor, sildenafil, in non-diabetic ED patients. Conversely, a PKC inhibitor, GF109203X, improved endothelial, neurogenic, and PDE5-inhibitor-induced relaxations and cGMP generation only in the CC in diabetic ED patients. Endothelial and PDE5-inhibitor-induced vasodilations of PRAs were potentiated only in diabetes. Improvements in endothelial function in diabetes were also achieved with a specific inhibitor of the PKCβ2 isoform or an NADPH-oxidase inhibitor, apocynin, which prevented PDBu-induced impairment in non-diabetic patients. PKC inhibition counteracted NO/cGMP impairment and endothelial dysfunction in diabetes-related ED, potentially improving response to PDE5 inhibition.

(013) Glycated Serum Albumin Decreases Connexin 43 Phosphorylation in the Corpus Cavernosum

Abstract Introduction Glycated serum albumin (GSA) is an early glycosylation product that participates in diabetic vascular complications, including retinopathy, nephropathy, neuropathy, and coronary artery disease. Elevated GSA levels and the associated damage to the corpus cavernosum might be limited to not only diabetic patients but also non-diabetic patients and even individuals with normal glucose levels. Objective This study aimed to examine the role of GSA in early damage to the corpus cavernosum and identify the pathways involved in GSA-induced endothelium damage. Methods Nine 8-week-old male Sprague-Dawley (SD) rats (250–300 g) were divided into the control (saline vehicle, n=3) and GSA (200 μg/kg, n=6) groups. The corpus cavernosum tissues were harvested. Phosphorylated and non-phosphorylated connexin 43 (Cx43), endothelial nitric oxide synthase (eNOS), phosphatidylinositol 3-kinase (PI3K), and serine-threonine kinase (Akt) were tested by immunohistochemistry and western blotting. Human umbilical vein endothelial cells (HUVECs) overexpressing Cx43 were used to analyze the Cx43 phosphorylation sites (S368, S262, Y265, S255, and S279/282) using western blotting. Results The expression of phosphorylated Cx43 in the penis was significantly lower in GSA-treated rats than in controls. The expression levels of p-Cx43, p-eNOS, p-PI3K, and p-Akt were significantly decreased in HUVECs exposed to GSA in dose- and time-dependent manners. The most significant impact on all four proteins was observed with 1 μg/mL of GSA for 12 h. Phosphorylation at the S368, S262, Y265, S255, and S279/282 sites of Cx43 was downregulated by GSA, and S368 was the most significantly suppressed phosphorylation site compared with the other sites. Conclusions GSA decreases the expression of p-Cx43 in the corpus cavernosum of rats. This effect might be also related to the decreased phosphorylation of p-eNOS, p-PI3K, and p-Akt, as well as by the downregulation of phosphorylation at the S368 site. Disclosure No.

(059) Effects of a Red-Light–Controllable Nitric Oxide Donor, NORD-1, on Diabetes Mellitus-Induced Erectile Dysfunction in Rats

Abstract Introduction Diabetes mellitus (DM) often causes erectile dysfunction (ED). Phosphodiesterase-5 inhibitor has limited effects on diabetes mellitus-induced erectile dysfunction (DMED). One contributing factor to this reduced effect is the decreased production of nitric oxide owing to neuropathy and endothelial impairment. To address this issue, we developed a red-light–controllable nitric oxide donor, NORD-1, that successfully enhanced erectile function in intact and cavernous nerve injury model rats. Objective In this study, we investigated whether NORD-1 and red-light irradiation could improve DMED in rats. Methods Seven-week-old Sprague–Dawley male rats were used. Rats in the DM and sham groups were intravenously administered streptozotocin 50 mg/kg and saline, respectively. One week after treatment, the blood glucose levels of rats in the DM group were found to be over 250 mg/dL. Five weeks after the treatment, we performed a functional study using the measurements of intracavernous pressure (ICP) under the stimulation of the cavernous nerve. The study was performed before and after NORD-1 treatment, both with and without light irradiation. Additionally, we performed an isometric tension study using corpus cavernosum from rats treated with either NORD-1 or a control compound, SiR650. Results The ICP/MAP ratio of the DM group was significantly lower than that of the sham group before and after NORD-1 treatment without light irradiation (both P<0.05). However, after NORD-1 treatment with light irradiation, the ICP/MAP ratios of the Sham and DM groups were substantially enhanced compared with that before and after NORD-1 treatment without light irradiation (all P<0.05). The ICP/MAP ratio of the DM group was similar to that of the Sham group under the normal condition before NORD-1 treatment by light irradiation. Moreover, systemic blood pressure was not affected by NORD-1 and light irradiation. In the isometric tension study, rat corpus cavernosum from rats treated with SiR650 showed no changes under red light in both the Sham and DM groups. However, the corpus cavernosum from rats treated with NORD-1 was strongly relaxed by red light in both groups. Conclusions NORD-1 and red-light irradiation could improve DMED in STZ-induced DM rats without lowering blood pressure. Disclosure No.

(066) A Low Androgen State Impairs Erectile Function by Suppressing EPAC1 in Rat Corpus Cavernosum Penis

Abstract Introduction The relationship among exchange proteins activated by cAMP 1(EPAC1), androgen and erectile function is still unknown. Objective To explore whether EPAC1 expresses in penile corpus cavernosum of rats and how EPAC1 affects erectile function under low androgenic conditions. Methods Thirty 8-week-old healthy male rats were randomly divided into six groups (n=5): sham operation (sham), castrated, castrated + testosterone replacement (castrated + T), sham + EPAC1 over-expression lentivirus (sham + EPAC1), castrated + empty lentivirus vector (castrated + empty vector), and castrated + EPAC1. Four weeks after the operation, the lentivirus vectors carrying the EPAC1 gene were injected into the corpus cavernosum penis tissues of the sham + EPAC1 and castrated + EPAC1 groups (1×108TU/ml, 20 μl per rat). A week after injection, the ratio of maximum intracavernous pressure to mean arterial pressure (ICPmax/MAP) and the levels of serum testosterone (T), nitric oxide (NO), the active form of ras homolog gene family, member A (RhoA-GTP), protein kinase B (AKT), phospho-AKT (p-AKT), endothelial nitric oxide synthase (eNOS), phospho-eNOS (p-eNOS), p-AKT/AKT, p-eNOS/eNOS and EPAC1 levels were measured. Results EPAC1 is primarily located in the cytoplasm of endothelial cells and smooth muscle cells in the rat corpus cavernosum penis. In comparison to the sham group, the T, ICPmax/MAP and NO levels of the castrated group were notably reduced (p < 0.01). Meanwhile, the RhoA-GTP concentration in the castrated + EPAC1 group was reduced in comparison with the castrated + empty vector group (p < 0.01). Compared with the castrated + empty vector group, the p-AKT/AKT, EPAC1 and p-eNOS/eNOS levels in the castrated + EPAC1 group were significantly increased (p < 0.05). Conclusions Androgen deficiency can suppress EPAC1 expression in the penile corpus cavernosum of rats, while the up-regulation of which can improve the erectile function of castrated rats. Disclosure Yes, this is sponsored by industry/sponsor: This study was supported by the Research Foundation of the Department of Human Resources and Social Security of Sichuan Province of Returned Scholars grant 2019-76. Clarification: No industry support in study design or execution.

(282) Penile Crural Dysplasia is a New Identified Factor for Erectile Dysfunction

Abstract Introduction Given the penile fibro-vascular assembly was just thoroughly interpreted recently and inspired by impotent patients' questions during daily practice, so does the penile venous stripping (PVS), which is deemed controversial thus far. Despite primary impotence (PI) being ascribed to psychogenic origin, in the large repository of PVS treating PI, some 5 % remain refractory in the last decade, an analysis deemed required. Objective We sought to report penile crural dysplasia or hypoplasia that prevents sustainability compared to most PVS males thus far. Methods A retrospective analysis was conducted internationally on 45 consecutive young men with PI from 2013 to 2023. They were allocated into the crural dysplasia group (CDG, n=8), defined as a 50% diameter difference between the largest penile crus and corresponding corpus cavernosum or a 25% diameter difference of bilateral penile crura, and no crural-dysplasia group (NCG, n=37). On an ambulatory basis under acupuncture-aided local anesthesia, neither electrocautery nor a suction apparatus is used, with a circumferential or semi-circumcision followed by a pubic longitudinal approach, the PVS entailed the erection-related vein, including stripping a deep dorsal vein, two cavernosal veins after each emissary's vein was firmly ligated closest to the outer tunic layer with a 6–0 nylon suture. In contrast, the four para-arterial veins were only segmentally ligated. The overlying fascia layers and skin were approximated with a 6–0 nylon and 5–0 chromic suture for the skin, as did the semi-circumcision wound if it existed. The abridged 5-item version of the International Index of Erectile Function (IIEF-5) score system and the erection hardness scale (EHS) were used to assess erection restoration; preoperative data were based on masturbation; additionally, a radio-opacity index was used for comparison of the femoral cortex and that of penile crus preoperative and postoperative, respectively. Follow-up was primarily made via either INTERNET or telephone yearly. After this May, we introduced an autologous venous patch to augment the crural hypoplasia with a promising outcome on two new patients. Statistically, IBM SPSS 21.0 was used. Results The follow-up time was from 0.1 to 10.0 years, averaging 5.7 ± 1.1 years in the CDG and NCG groups, respectively. The blood loss is negligible. There is no difference between the operation time (4.9−0.8 hours vs. 4.8 ± 0.7 hours, p> 0.88) for the CG and EG group, respectively. In both groups, there is a significant of IIEF-5 scores, EHS (5.7±2.0 vs. 15.9±2.1, 1.8±0.8 vs. 2.5±0.6; 5.8 ±2.1 vs. 22.4±1.1, 1.8±0.9 vs. 3.6±0.3; both P<0.001) between the CDG and NCG. The preoperative radio-opacity of penile crura was unexceptionally enhanced postoperatively. In the NCG, 89.1% (33/37) are gratified; in contrast, 37.5% are satisfied in the CDG five years postoperatively, although surgery benefit is unexceptional reported. A close follow-up is going on with the two new males. Conclusions Penile crural hypoplasia is an unidentified contributor to primary impotence, although a larger sample size and longer-term follow-up are warranted. Disclosure No.

(168) Combining Varicocelectomy and Penile Venous Stripping for Patients with Varicocele and Erectile Dysfunction on an Ambulatory Basis

Abstract Introduction Varicocelectomy is a well-established procedure for varicocele testis over one century. It has recently been advanced to minimally invasive surgery types such as laparoscopic or Da Vinci varicocelectomy. Should we question why the approach is beyond the shortest-cut route? Despite penile venous surgery is still cautious in treating patients with erection dysfunction (ED), an anatomy-based penile venous stripping has been conducted for decades, however. It is common to encounter patients with two disease entities. Could the shortest-cut approach be available? Objective We sought to report a novel approach for this purpose on an ambulatory basis. Methods From October 2013 to October 2020, 68 men aged from 28 to 68 years consulted us with erectile dysfunction and varicocele testis, at least grade II. Dual pharmaco-cavernosography and sonography are the primary tools for confirmation, respectively. The abridged five-item version of the International Index of Erectile Function (IIEF-5) erection hardness scales (EHS) was used to assess erection restoration. Acupuncture-assisted local anesthesia was routinely applied on an ambulatory basis. Neither electrocautery nor suction apparatus was used in the entire procedure. They underwent penile venous stripping (PVS) via circumferential approach and, subsequently, to the deeper portion of the erection-related veins via a pubic longitudinal method; later, bi-lateral varicocelectomy was conducted while the spermatic cord was hooked out. The PVS entails stripping one deep dorsal vein and two cavernosal veins after every specific emissary vein is microscopically ligated closest to the outer tunica, whereas the para-arterial veins are segmentally ligated. The visibility of the pampiniform plexus was enhanced by the squeezing method. Finally, the wound was meticulously repaired using a 6–0 nylon suture. Postoperative cavernosography was routinely made for comparison. Radiopacity was used to compare the penile crus, Corpora cavernosa, and femur cortex. Follow-up was made via INTERNET every six months, one year, and then yearly. Results The average follow-up period was 5.2±1.2 years, and the surgery time was 6.3±1. 5 hours, respectively. The blood loss is negligible. The radiopacity was unexceptionally enhanced postoperatively. There was a significant difference (P<0.01) between the preoperative (9.9±2.6) vs. Postoperative IIEF-5 scores (20.6±2.4). The EHS improved on at least one scale. Overall, the post-ejaculation testicular aching was no more bothered in all 23 patients who sustained preoperatively in 6 months postoperatively. Conclusions This combination of physiologically penile venous stripping and bilateral varicocelectomy appears feasible for patients with erectile dysfunction and varicocele via a circumferential and pubic approach on an ambulatory basis. Disclosure No.

(274) BMP2 Restores Erectile Dysfunction Through Neurovascular Regeneration and Fibrosis Reduction in Diabetic Mice

Abstract Introduction The odds of erectile dysfunction (ED) are thrice more prevalent in diabetes. Severe peripheral vascular and neural damage in diabetic patients responds poorly to PDE5 inhibitors. However, bone morphogenetic protein 2 (BMP2) is known to be involved in angiogenesis. Objective To assess the efficacy of BMP2 stimulating angiogenesis and augmenting nerve regeneration in a mouse model of diabetic-induced erectile dysfunction. Methods The induction of diabetes mellitus was done by streptozotocin (STZ, 50 mg/kg daily) administered intraperitoneally for five successive days to male C57BL/6 mice that were 8 weeks old. Eight weeks post inductions, animals were allocated to one of five groups: a control group, an STZ-induced diabetic mouse group receiving two intra-cavernous 20 μL PBS injections, or one of three BMP2 groups administered two injections of BMP2 protein (1μg, 5 μg, or 10 μg) diluted in 20 μL of PBS with three days interval between the first and second injection. The erectile functions were assessed two weeks after PBS or BMP2 protein injections by recording the ICP (intracavernous pressure) through cavernous nerve electrical stimulation. Angiogenic activities also nerve regenerating effects of BMP2 were determined in penile tissues, aorta, vena cava, the main pelvic ganglions, the dorsal roots, and from the primary cultured MCECs (mouse cavernous endothelial cells). Moreover, fibrosis-related factors protein expressions were evaluated by western blot. Results Erectile function recovery to 81% of the control value in diabetic mice was found with intra-cavernous BMP2 injection (5 μg/20 μL). Pericytes and also endothelial cells were extensively restored. It was confirmed that angiogenesis was promoted in the corpus cavernosum of diabetic mice treated with BMP2 through increased ex vivo sprouting of aortic rings, vena cava and penile tissues, and migration and tube formation of MCECs. BMP2 protein enhanced cell proliferation and reduced apoptosis in MCECs and penile tissues, and promoted neurite outgrowth in major pelvic ganglia and dorsal root ganglia under high-glucose conditions. Furthermore, BMP2 suppressed fibrosis by reducing MCEC fibronectin, collagen 1, and collagen 4 levels under high-glucose conditions. Conclusions BMP2 modulates neurovascular regeneration and inhibits fibrosis to revive the mice's erection function in diabetic conditions. Our findings propose that the BMP2 protein represents a novel and promising approach to treating diabetes-related erectile dysfunction (ED). Disclosure No.

(163) Is There a Place for Immediate 3-Component Prosthesis Implantation Following Priapism?

Abstract Introduction One of the most difficult challenges in prosthetic urology is the insertion of penile implants into corpora scarred from an episode of priapism. In cases of scarred penile cavernosal bodies, surgery becomes challenging even for experienced surgeons, as it can be very difficult to dilate the corpora. Objective Usually, the initial insertion of a malleable device is used as a temporary measure, to maintain the penile length and simplify the subsequent insertion of an inflatable one. So our objective is to decrease the number of surgeries from 2 to 1. Methods In this case, we dilated the corpora cavernosa initially with Metzenbaum scissors thoroughly and carefully. We placed the tip of the scissors at the outer side of each cavernous body (away from the urethra) and advanced it to the tip of the corpus cavernosum. Then, we used the cavernotomes Results Till now the prostheses are functional. We do believe that in certain cases, with the right choice of the patient, the implant of the IPP after priapism is a viable solution Conclusions Cavernotomes are a good option for dilating the fibrotic corpora. And it is safe Disclosure No.

(018) Long Term Outcome of Tachosil Patching of the Penile Tunica Albuginea Defect in the Dog: Histological and Hemodynamic Results

Abstract Introduction The need for patching of the penile tunica albuginea (TA) might arise during surgery for Peyronie’s disease with or without a penile prosthesis. Clinically, TachoSil has evolved as an off-the-shelf hemostatic graft that does not need suturing. Results in patients are encouraging. However, its histopathological fate and its impact on the hemodynamics of erection are not known. Objective We evaluate the long-term histopathology and pharmacologically induced erection after Tachosil patching of the TA in dogs. Methods Under general anesthesia, the penis of two adult male beagle dogs was dissected through a midline incision, and TA was exposed. The femoral artery was cannulated and connected to an invasive pressure monitor to record BP. Intracavernous pressure (ICP) was measured on each cavernous side separately, as a complete septum isolates the two compartments of the penis. A 21-gauge butterfly needle was placed on either side proximally. Five minutes were allowed before taking baseline ICP. Ten mg of papaverine hydrochloride was injected intracavernosal. ICP was measured at 2 to10-min time points. On the left side, 2 cm proximal to the glans of the penis, a full-thickness defect was created in TA 1 cm long and 0.5 cm wide (Fig. 1. A, B &C). Four transverse incisions 1 cm long were made on the right side and placed 0.5 cm apart, exposing the corpus cavernosum (Fig. 1. D). A Tachosil patch (Takeda, Japan) was fashioned and applied to cover the defects. Proline 5/0 sutures were placed, marking the proximal and distal ends of the graft areas. The fascia, subcutaneous tissue, and skin were closed with absorbable sutures. Six months later, each dog was anesthetized, and the penis was dissected free from the covering fascia. Invasive BP and ICP measurements were repeated at baseline and after 10 mg papaverine injection. Silk and proline sutures were placed to identify the distal end and the left side of the penis. The penis was excised from the base of the glans penis distally to its root, at least 6 cm proximally and fixed in 10% formaldehyde solution. Transverse blocks of the penis were cut at 3 mm intervals and fixed in paraffin. Sections from each block were stained with H&E and trichrome and examined by a urology pathologist. Descriptive statistics are provided. Results Gross appearance showed a well-healed scar, and the subcutaneous tissue did not show significant adhesions. The graft site was impossible to distinguish, and the sutures were not visible. ICP measurement did not show a drop in pressure pre- and post-surgery (Fig. 2). Histologically, minimal foreign body reaction was seen, and the tunica albuginea was completely regenerated (Fig. 3). The underlying cavernous tissue did not show inflammation or necrosis. Conclusions Long-term histological results of Tachosil patching in the dog show complete tunica albuginea regeneration with minimal tissue reaction and no underlying cavernous tissue pathology. Hemodynamically the intracavernous pressure response to papaverine is maintained. Although only two animals are presented here, the results are striking. Further experimentation with more animals is warranted to support these findings. Disclosure No.

(152) Efficiency Improvement Veno-Occlusive Surgeries for Treatment of Venous Leak with Autologous Stem Cell, VEGF and PRP

Abstract Introduction The venous leakage is one of the most often reason of erectile dysfunction (ED) in young and middle age men. The main reason of venous leakage or veno-occlusive Erectile Dysfunction (VOED) is the insufficiency venous obstruction under tunica albuginea of corpora cavernosa. Accordingly all types of veno-occlusive operations have particular and short term effect up to renovation of venous leakage in half year. Conservative treatment of VOED with PDE-5 has a low or mild effectiveness. Evermore young patients deny penile prosthesis implantation for psychological reason. Objective We want to stimulate growth of endothelial valves under tunica albuginea with injections autological mesenchymal stem cells (ASC) and autological VEGF (Vascular endothelial growth factor) and combine it with veno-occlusive surgeries. Methods 2012–2022 we treated 178 patients with VOED. The average patient age is 36.5 +4.1 years. Patients with prostatitis or depression/anxiety were excluded from the investigation or treated previously. We embolizated deep dorsal and Santorini plexus veins for patients with distal form of VOED–47 patients -Group 1. We ligated deep dorsal and penile veins for proximal form of VOED – 68 patients – Group 2. And we made both methods together for 65 patients –Group 3 with combination of proximal and distal leak. Patients with only surgical methods created subgroup A – 105 men. For improving of veno-occlusive mechanism for 73 patients (subgroup B) we injected to each corpus cavernosa 1 mln of autological stem cells 6 times (2 times before, during surgery and 3 times after surgery) each month and we performed 15 microinjections of VEGF each 10 days. Then we compared short (2 months) and long term (10 months) results. Results The efficacy of surgical treatment according to subjective data (questionnaires on IIEF-5) in 2 months was almost equal (16.7+3.1 and 16.9+3.0), but in 10 months significantly higher in SubGroup B(14.3+3.2 and 19.6+3.4). According to Doppler Penile Ultrasound in 10 months adding microinjections ASC and VEGF to surgery significantly improves Erectile function (absence of venous leakage) 56.4% - subgroup A and 87.4% - subgroup B. Only 6.8% patients subgroup B (opposite to 35.9% subgroup A) have to take PDE-5 inhibitors for maintain erectile function. Conclusions Half year injections of ASC and VEGF improve of veno-occlusive mechanism and increases effectiveness and long term result of veno-occlusive operations for treatment of VOED. Combine occlusive method (embolisation and ligation of veins) has the highest effectiveness and should be used in different types of leakage. Disclosure No.

Galectin-3 is involved in inflammation and fibrosis in arteriogenic erectile dysfunction via the TLR4/MyD88/NF-κB pathway

Galectin-3 (Gal-3) is a multifunctional protein that has been linked to fibrosis and inflammation in the cardiovascular system. In this study, we examined the impact of Gal-3 on inflammation and fibrosis in patients with arteriogenic erectile dysfunction (A-ED) and the underlying mechanisms involved. To induce arterial injury, we utilized cuffs on the periaqueductal common iliac arteries of Sprague‒Dawley (SD) rats and administered a high-fat diet to co-induce local atherosclerosis. Our results showed that we successfully developed a novel A-ED model that was validated based on histological evidence. In vivo, the vascular lumen of rats subjected to a high-fat diet and cuff placement exhibited significant narrowing, accompanied by the upregulation of Gal-3, Toll-like receptor 4 (TLR4), and myeloid differentiation primary response protein 88 (MyD88) expression in the penile cavernosa. This led to the activation of nuclear factor kappa B 65 (NF-κB-p65), resulting in reduced intracavernosal pressure, endothelial nitric oxide synthase expression, and smooth muscle content, promoting inflammation and fibrosis. However, treatment with Gal-3 inhibitor-modified citrus pectin (MCP) significantly normalized those effects. In vitro, knocking down Gal-3 led to a significant reduction in TLR4, MyD88, and NF-κB-p65 expression in corpus cavernosum smooth muscle cells (CCSMCs), decreasing inflammation levels. In conclusion, inhibiting Gal-3 may improve A-ED by reducing inflammation, endothelial injury, and fibrosis in the penile corpus cavernosum through the TLR4/MyD88/NF-κB pathway. These findings highlight the potential therapeutic target of Gal-3 in A-ED.

Hypospadias-associated penile curvature assessment and management: A global survey of current practice

Our goal was to assess how surgical management of hypospadias-associated penile curvature (HAPC) varies across continents, focusing on factors that influence assessment and decision-making. Members of the European Society of Pediatric Urology (ESPU), Society of Pediatric Urology (SPU), and Hypospadias International Society (HIS) participated in an anonymous, 34-question online survey addressing pre-, intra-, and postoperative elements of HAPC evaluation and management. A selection of intraoperative photos were included in the survey to investigate the prevailing surgical approaches and identify management patterns. Out of the 267 participants, 38.4% of them are located in Europe. Visual estimation was the predominant approach for evaluating HAPC, although being regarded as the least dependable compared to other techniques. Surgeons who performed more than 40 cases per year were more inclined to use goniometers and had varying degrees of HAPC that were considered acceptable without requiring any correction (P<.001). Out of 58% of respondents, a significant number reported regular utilization of artificial erection tests for all categories of hypospadias. Surgeons with fewer than 10 years of expertise commonly utilized erection test as part of their regular practice. A tourniquet was employed to maintain sufficient intra-corporeal pressure, by134 (50%). 116 participants (43%) inject Saline through the corpora cavernosa through the glans, while 150 (56%) administer saline from the lateral aspect. Moreover, the decision-making process differed based on the intraoperative picture scenarios of mild to moderate penile curvature during erection testing. Contrary to temperatures ranging from 25o to 35o, decision-making in cases with less severe degrees of HAPC was uncomplicated. This survey reveals a wide range of surgical practicepatterns in the assessment and management of HAPC. To our knowledge, this global surveyof HAPC practice is the largest to date and could aid in developing new guidelines in pediatricurology. These findings may also provide a foundation for future prospective multinational studies.

Artificial cavernosa-like tissue based on multibubble Matrigel and a human corpus cavernous fibroblast scaffold.

Ex vivo tissue culture of the human corpus cavernosum (CC) can be used to explore the tissue structural changes and complex signaling networks. At present, artificial CC-like tissues based on acellular or three-dimensional (3D)-printed scaffolds are used to solve the scarcity of primary penis tissue samples. However, inconvenience and high costs limit the wide application of such methods. Here, we describe a simple, fast, and economical method of constructing artificial CC-like tissue. Human CC fibroblasts (FBs), endothelial cells (ECs), and smooth muscle cells (SMCs) were expanded in vitro and mixed with Matrigel in specific proportions. A large number of bubbles were formed in the mixture by vortexing combined with pipette blowing, creating a porous, spongy, and spatial structure. The CC FBs produced a variety of signaling factors, showed multidirectional differentiation potential, and grew in a 3D grid in Matrigel, which is necessary for CC-like tissue to maintain a porous structure as a cell scaffold. Within the CC-like tissue, ECs covered the surface of the lumen, and SMCs were located inside the trabeculae, similar to the structure of the primary CC. Various cell components remained stable for 3 days in vitro , but the EC content decreased on the 7 th day. Wingless/integrated (WNT) signaling activation led to lumen atrophy and increased tissue fibrosis in CC-like tissue, inducing the same changes in characteristics as in the primary CC. This study describes a preparation method for human artificial CC-like tissue that may provide an improved experimental platform for exploring the function and structure of the CC and conducting drug screening for erectile dysfunction therapy.

(156) Morphometrix Tissue Segmentation Technology as a Diagnostic Aid in the Evaluation of Vasculogenic Causes of Erectile Dysfunction

Abstract Introduction Morphometrix Imaging Technologies Inc. (MPX) Tissue Segmentation Technology (TST) isolates and processes the component of ultrasound reflective signals associated with coherent specular reflection at the liquid spaces in living tissue. The software identifies and quantifies the hypoechoic structures in B-Mode Ultrasound Scans produced by these reflections and thereby profiles liquid spaces in the tissue created by blood and lymphatic vessels as a proxy for vascular intensity. It then derives tissue segment counts (TSC) as a final quantification step. Unlike SHIM Scores, TST provides a quantitative assessment of the vascular health of the erectile tissue. Objective The goal of the study was to determine whether TSC can predict a response to regenerative treatments for ED. We retrospectively studied the efficacy of MPX TST in assessing the vascularity of the corpus cavernosa (CC) and compared the findings to SHIM scores before and after Shockwave therapy (SWT). MPX can assess penile vascularity in the flaccid state using TSC and can calculate cross-sectional area and volume. Methods Retrospective study of 57 men, average age 54.9 with ED. B-mode Ultrasound video scans were performed on the penis in the flaccid state before and after treatment completion and processed through MPX to obtain the TSC which were compared to IIEF-5 SHIM scores. A typical treatment involved multiple sessions of SWT and PRP penile injection. Subjects were divided into three groups based on response to treatment and correlation with SHIM Scores: Group 1 – Good Responders &amp; Good Correlation with SHIMs, Group 2 – Poor &amp; Non-Responders &amp; Good Correlation with SHIMs, Group 3 – Good &amp; Poor Responders &amp; Non-Correlation with SHIMs. Results Overall we had an 80.7% correlation between TSC and the SHIM Score results. The average SHIM score increased to 15.9 from 10.6, (p&amp;lt;0.006). The average TSC in the left CC increased to 25 from 17.3, (p&amp;lt;0.002). The average TSC in the right CC increased to 24.7 from 17.9, (p&amp;lt;0.002). 54.9% (34 patients) were good responders and the SHIM scores correlated well with TSC. The average SHIM score increased to 17.5 from 10.8, (p&amp;lt;0.001). The average TSC in the left CC increased to 28.1 from 15.3, (p&amp;lt;0.001). The average TSC in the right CC increased to 31.2 from 17.1, (p&amp;lt;0.003). 21.1% (12 patients) were poor responders and the SHIM scores correlated well with TSC. The average SHIM score increased 10.3 from 9.4, (p&amp;lt;0.554). The average TSC in the left CC declined to 13.5 from 15.5, (p&amp;lt;0.559). The average TSC in the right CC declined slightly to 14.9 from 12.5, (p&amp;lt;0.268). 19.3% (11 patients) were a mixture of good and poor responders and the SHIM scores did not correlate well with TSC. The average SHIM score increased to 15.1 from 11.3, (p&amp;lt;0.103). The average TSC in the left CC declined to 25.5 from 26.8, (p&amp;lt;0.919). The average TSC in the right CC declined to 25.5 from 25.7, (p&amp;lt;0.975). Conclusions MPX tissue segmentation software can provide quantitative information about the vascularity of the corpus cavernosa and can differentiate responders to treatment from non-responders. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Morphometrix.