Restoration Of Erectile Function Research Articles

Improved Health Care Utilization Among Men With Depression Undergoing Inflatable Penile Prosthesis in a U.S. Commercial Population.

We evaluated depression-related health care resource utilization and antidepressant prescription medication utilization among commercially insured men in the United States who underwent inflatable penile prosthesis (IPP) implantation between January 1, 2007 and December 31, 2020, and who received a depression diagnosis in the year preceding the IPP procedure. A total of 11,177 patients received an IPP during the index period, 808 of whom were diagnosed with depression. A statistically significant reduction in overall depression-related health care visits occurred from pre- to post-IPP, decreasing from 4.9 to 3.8, p < .001. In addition, there was a significant reduction in depression-related inpatient visits (0.07 vs. 0.03, p = .02) and office visits (4.25 vs. 3.29, p < .001) from pre- to post-IPP. Of the 678 men who received an antidepressant medication within 1 year prior to their IPP date, 15% stopped antidepressant medication use entirely post-IPP. Among patients with continued antidepressant medication use post-IPP (n = 574), there was a significant decrease in the number of prescriptions (7.55 vs. 8.09, p < .0001) and refills (7.52 vs. 8.11, p = .0015), with a higher likelihood of discontinuation (17.6% vs. 10.5%, p < .0001) and a lower proportion of days covered (0.79 vs. 0.83, p = .0004) post-IPP compared with pre-IPP. In conclusion, IPP was associated with reduced depression-related health care utilization and antidepressant medication use among recipients. This suggests potential mental health benefits for IPP recipients beyond restoration of erectile function. Comprehensive insurance coverage for IPP, especially for men with depression, may be beneficial to both patients and insurers.

Photobiomodulation as a Potential Therapy for Erectile Function: A Preclinical Study in a Cavernous Nerve Injury Model.

To identify the optimal photobiomodulation (PBM) parameters using molecular, histological, and erectile function analysis in cavernous nerve injury. A cavernous nerve injury was induced in 8-week-old C57BL/6J male mice that were subsequently divided randomly into age-matched control groups. Erectile function tests, penile histology, and Western blotting were performed 2 weeks after surgery and PBM treatment. The PBM treatment was administered for five consecutive days with a light-emitted diode (LED) device that delivers 660 nm±3% RED light, and near infra-red 830 nm±2% promptly administered following nerve-crushing surgery and achieved a notable restoration of erectile function approximately 90% of the control values. Subsequent in-vitro and ex-vivo analyses revealed the regeneration of neurovascular connections in both the dorsal root ganglion and major pelvic ganglion, characterized by the sprouting of neurites. Furthermore, the expression levels of neurotrophic, survival, and angiogenic factors exhibited a substantial increase across all groups subjected to PBM treatment. The utilization of PBM employing LED with 660 nm, 830 nm, and combination of both these wavelengths, exhibited significant efficacy to restore erectile function in a murine model of cavernous nerve injury. Thus, the PBM emerges as a potent therapeutic modality with notable advantages such as efficacy, noninvasiveness, and non-pharmacological interventions for erectile dysfunction caused by nerve injury.

The effectiveness of medical penile rehabilitation after radical prostatectomy

Background. Among the drug methods of penile rehabilitation in patients after nerve-sparing prostatectomy, the use of phosphodiesterase-5 (PDE-5) inhibitors is proposed as the first line of therapy, which have shown high efficiency, ease of use, good tolerability and safety, improving the quality of life of patients.Aim. To evaluate the effectiveness of drug-induced penile rehabilitation after nerve-sparing prostatectomy in the restoration of erectile function (EF) with an analysis of the factors influencing it.Materials and methods. The study included 108 patients with localized prostate cancer who underwent nerve-sparing prostatectomy. All patients were randomized into two groups. In Group 1 patients did not receive drug therapy for the prevention and treatment of erectile dysfunction. In Group 2 patients in the postoperative period received daily PDE-5 inhibitors (tadalafil) at a minimum dosage of 5 mg for 12 months as a drug therapy. Initially and at the annual stage of the study, the state of EF, erectile rigidity, night penile test, and quality of life were assessed. An analysis was also made of the factors affecting the preservation of EF one year after nerve-sparing radical prostatectomy.Results. The best reliable results in terms of maintaining EF at the annual stage of the study were obtained in the group whose patients received postoperative drug therapy with PDE-5 inhibitors. It was possible to identify the most significant factors influencing the state of EF in the postoperative period after radical prostatectomy: the type of operation – bilateral nerve sparing, taking PDE-5 inhibitors, the patient’s age, the presence/absence of diabetes mellitus, the state of EF (International Index of Erectile Function-5 value) before the operation.Conclusion. Daily intake of PDE-5 inhibitors at a low dose of 5 mg is indicated for patients after nerve-sparing prostatectomy as an effective means of penile rehabilitation in order to preserve EF, as it provides better results compared to no drug therapy. Patients who meet criteria such as young age, no diabetes, high preoperative International Index of Erectile Function-5 levels may benefit most from nerve-sparing surgical techniques and early postoperative participation in a penile rehabilitation program for erectile dysfunction.

Functional recovery of injured cavernous nerves achieved through endogenous nerve growth factor-containing bioactive fibrous membrane.

Radical prostatectomy is a highly successful treatment for prostate cancer, among the most prevalent manifestations of the illness. Damage of the cavernous nerve (CN) during prostatectomy is the main cause of postoperative erectile dysfunction (ED). In this study, the capability of a personalized bioactive fibrous membrane to regenerate injured CN was investigated. The fibrous membrane bioactivity is conferred by the selectively bound nerve growth factor (NGF) present in the rat urine. In a rat model of bilateral CN crush, the implanted bioactive fibrous membrane induces CN regeneration and restoration of erectile function, showing a significantly increased number of smooth muscle cells and content of endothelial and neuronal nitric oxide synthases (eNOS; nNOS). In addition, the bioactive fibrous membrane promotes nerve regeneration by increasing the number of myelinated axons and nNOS-positive cells, therefore reversing the CN fibrosis found in untreated rats or rats treated with a bare fibrous membrane. Therefore, this personalized regenerative strategy could overcome the recognized drawbacks of currently available treatments for CN injuries. It may constitute an effective treatment for prostate cancer patients suffering from ED after being subject to radical prostatectomy. STATEMENT OF SIGNIFICANCE: The present work introduces a unique strategy to address post-surgical ED resulting from CN injury during pelvic surgery (e.g., radical prostatectomy, radical cystoprostatectomy, abdominoperineal resection). It comprises a bioactive and cell-free fibrous implant, customized to enhance CN recovery. Pre-clinical results in a rat model of bilateral CN crush demonstrated that the bioactive fibrous implant can effectively heal injured CN, and restore penile structure and function. This implant selectively binds NGF from patient fluids (i.e. urine) due to its functionalized surface and high surface area. Moreover, its local implantation reduces adverse side effects. This tailored regenerative approach has the potential to revolutionize the treatment of ED in prostate cancer patients following radical prostatectomy, overcoming current treatment limitations.

Effects of platelet-rich plasma glue placement at the prostatectomy site on erectile function restoration and cavernous nerve preservation in a nerve-sparing prostatectomy rat model

BackgroundDespite the widespread use of nerve-sparing prostatectomy techniques, the incidence of post-operative erectile dysfunction (ED) remains high. Early intracavernous (IC) injection of platelet-rich plasma (PRP) after nerve crushing improves erectile function (EF) in rats by promoting cavernous nerve (CN) regeneration and preventing structural changes in the corpus cavernosum. However, the neuroprotective effects of the in situ application of PRP glue in rats after CN-sparing prostatectomy (CNSP) remain unclear. AimThis study aimed to investigate the effects of PRP glue treatment on EF and CN preservation in rats after CNSP. MethodsAfter prostatectomy, male Sprague–Dawley rats were treated with PRP glue, IC PRP injection, or their combination. The intracavernous pressure (ICP), mean arterial pressure (MAP), and CN preservation status in the rats were evaluated after 4 weeks. Results were corroborated using histology, immunofluorescence, and transmission electron microscopy. ResultsThe PRP glue-treated rats showed 100% CN preservation and significantly higher ICP responses (the ratio of maximum ICP to MAP (0.79 ± 0.09)) than the CNSP rats (the ratio of maximum ICP to MAP (0.33 ± 0.04)). PRP glue also significantly increased neurofilament-1 expression, indicating its positive effect on the CNs. Furthermore, this treatment significantly increased the expression of α-smooth muscle actin. Electron micrographs revealed that PRP glue preserved the myelinated axons and prevented atrophy of the corporal smooth muscle by maintaining the adherens junctions. ConclusionsThese results indicate that PRP glue is a potential solution for EF preservation by neuroprotection in patients with prostate cancer who are likely to undergo nerve-sparing radical prostatectomy.

Vitamin D3 improved erectile function recovery by regulating autophagy and apoptosis in a rat model of cavernous nerve injury.

Vitamin D3 is an important element in improving erectile function. However, the mechanisms of vitamin D3 remain unknown. Thus, we explored the effect of vitamin D3 on erectile function recovery after nerve injury in a rat model and investigated its possible molecular mechanisms. Eighteen male Sprague-Dawley rats were used in this study. The rats were randomly divided into three groups: the control, bilateral cavernous nerve crush (BCNC), and BCNC + vitamin D3 groups. BCNC model was established in rats by surgery. The intracavernosal pressure and the ratio of intracavernosal pressure to mean arterial pressure were utilized to evaluate erectile function. Masson trichrome staining, immunohistochemistry, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling and western blot analysis were performed on penile tissues to elucidate the molecular mechanism. The results indicated that vitamin D3 alleviated hypoxia and suppressed the fibrosis signalling pathway by upregulating the expression of eNOS (p = 0.001), nNOS (p = 0.018) and α-SMA (p = 0.025) and downregulating the expression of HIF-1α (p = 0.048) and TGF-β1 (p = 0.034) in BCNC rats. Vitamin D3 promoted erectile function restoration by enhancing the autophagy process through decreases in the p-mTOR/mTOR ratio (p = 0.02) and p62 (p = 0.001) expression and increases in Beclin1 expression (p = 0.001) and the LC3B/LC3A ratio (p = 0.041). Vitamin D3 application improved erectile function rehabilitation by suppressing the apoptotic process through decreases in the expression of Bax (p = 0.002) and caspase-3 (p = 0.046) and an increase in the expression of Bcl2 (p = 0.004). Therefore, We concluded that vitamin D3 improved the erectile function recovery in BCNC rats by alleviating hypoxia and fibrosis, enhancing autophagy and inhibiting apoptosis in the corpus cavernosum.

Comparison of the therapeutic effects of human umbilical cord blood-derived mesenchymal stem cells and adipose-derived stem cells on erectile dysfunction in a rat model of bilateral cavernous nerve injury.

Background: Cavernous nerve injury (CNI) is the leading cause of erectile dysfunction (ED) after radical prostatectomy and pelvic fracture. Transplantation of human adipose-derived stem cells (ASCs) has been widely used to restore erectile function in CNI-ED rats and patients. Umbilical cord blood-derived MSCs (CBMSCs) are similarly low immunogenic but much primitive compared to ASCs and more promising in large-scale commercial applications due to the extensive establishment of cord blood banks. However, whether CBMSCs and ASCs have differential therapeutic efficacy on CNI-ED and the underlying mechanisms are still not clear. Materials and methods: A bilateral cavernous nerve injury (BCNI) rat model was established by crushing the bilateral cavernous nerves. After crushing, ASCs and CBMSCs were intracavernously injected immediately. Erectile function, Masson staining, and immunofluorescence analyses of penile tissues were assessed at 4 and 12 weeks. PKH-26-labeled ASCs or CBMSCs were intracavernously injected to determine the presence and differentiation of ASCs or CBMSCs in the penis 3 days after injection. In vitro experiments including intracellular ROS detection, mitochondrial membrane potential assay, EdU cell proliferation staining, cell apoptosis assay, and protein chip assay were conducted to explore the underlying mechanism of CBMSC treatment compared with ASC treatment. Results: CBMSC injection significantly restored erectile function, rescued the loss of cavernous corporal smooth muscles, and increased the ratio of smooth muscle to collagen. PKH-26-labeled CBMSCs or ASCs did not colocalize with endothelial cells or smooth muscle cells in the corpus cavernosum. Moreover, the conditioned medium (CM) of CBMSCs could significantly inhibit the oxidative stress and elevate the mitochondria membrane potential and proliferation of Schwann cells. Better therapeutic effects were observed in the CBMSC group than the ASC group both in vivo and in vitro. In addition, the content of neurotrophic factors and matrix metalloproteinases in CBMSC-CM, especially NT4, VEGF, MMP1, and MMP3 was significantly higher than that of ASC-CM. Conclusion: Intracavernous injection of CBMSCs exhibited a better erectile function restoration than that of ASCs in CNI-ED rats owing to richer secretory factors, which can promote nerve regeneration and reduce extracellular matrix deposition. CBMSC transplantation would be a promising therapeutic strategy for CNI-ED regeneration in the future.

Loss of penile length following radical prostatectomy

Introduction. The majority of patients who undergo radical prostatectomy, apart from loss of sexual function, note a decrease in penis size which negatively affects their self-esteem. Penile rehabilitation is a set of measures aimed at recovery of sexual function to improve the quality of life.Objective. To analyze various options for penile rehabilitation in order to choose a method for preventing penis size reduction in patients undergoing nerve-sparing radical prostatectomy.Materials and methods. Patients who undergo radical prostatectomy (n = 83) at status flaccid and status erect were measured: length, circumference of the base, body and glans penis (mm) at different periods of penile rehabilitation. As a control, the tumescence coefficient was determined using pharmacodopplerography. All results were evaluated before, at the 6th and 12th months after radical prostatectomy.Results. Depending on the type of restoration of erectile function, the patients were divided into several groups: group 1 – men without penile rehabilitation; group 2 – patients treated with phosphodiesterase inhibitors of type 5; group 3 – using vacuum erection device (VED) and group 4 – taking combined penile rehabilitation. Medians of tumescence coefficient in group 1 on the 6th and 12th months was 2.7 (2.4; 3.1) and 2.6 (1.9; 2.9), in group 2 – 2.8 (2.2; 3.5) and 2.9 (2.2; 3.5), in group 3 – 2.7 (2.3; 3.3) and 2.8 (2.3; 3.3), in group 4 – 3.0 (2.2; 3.2) and 3.1 (2.1; 3.2), respectively (p &lt;0.05).Conclusion. The determination of the tumescence coefficient in dynamics showed more significant results throughout the entire observation period. Combined penile rehabilitation is an effective method of restoring erectile function and also allows to maintain the size of the penis at all follow-up periods.

MP38-01 BIOACTIVE FIBROUS MEMBRANE CONTAINING ENDOGENOUS NERVE GROWTH FACTOR PROMOTES CELLULAR AND FUNCTIONAL RECUPERATION OF IMPAIRED CAVERNOUS NERVE: AN IN VIVO ANIMAL STUDY

You have accessJournal of UrologyCME1 May 2022MP38-01 BIOACTIVE FIBROUS MEMBRANE CONTAINING ENDOGENOUS NERVE GROWTH FACTOR PROMOTES CELLULAR AND FUNCTIONAL RECUPERATION OF IMPAIRED CAVERNOUS NERVE: AN IN VIVO ANIMAL STUDY Paulo Mota, Marta Casanova, Helena Vala, Carmen Nóbrega, Alain Morais, Catarina Silva, Sara Anacleto, Alexandre Barros, Rui Reis, Estêvão Lima, Albino Martins, and Nuno Neves Paulo MotaPaulo Mota More articles by this author , Marta CasanovaMarta Casanova More articles by this author , Helena ValaHelena Vala More articles by this author , Carmen NóbregaCarmen Nóbrega More articles by this author , Alain MoraisAlain Morais More articles by this author , Catarina SilvaCatarina Silva More articles by this author , Sara AnacletoSara Anacleto More articles by this author , Alexandre BarrosAlexandre Barros More articles by this author , Rui ReisRui Reis More articles by this author , Estêvão LimaEstêvão Lima More articles by this author , Albino MartinsAlbino Martins More articles by this author , and Nuno NevesNuno Neves More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002592.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate cancer is a frequent disease and the radical prostatectomy one of the most used treatment when the cancer is localized. This procedure commonly causes erectile dysfunction (ED) by injure the cavernous nerve (CN) during the surgery.With this research we investigate the ability of a bioactive fibrous membrane (FM) to regenerate the damaged CN in a rat model of CN injury. METHODS: Male Sprague–Dawley (SD) rats were distributed by 4 experimental groups: sham (only a lower midline abdominal incision), negative control (lower midline abdominal incision with pelvic dissection and CN crush but no FM implantation), electrospun fibrous membrane [eFM] (with CN crush and FM implantation) and electrospun fibrous membrane biofunctionalized with NGF from rat urine [eFM-uNGF] (with CN crush). Function was evaluated five weeks later after an injection of apomorphine by glans observation (visual scoring) and intracavernous pressure (ICP) measurements. Neurogenic genes expression and Histological and Immunohistochemical analysis of CN and cavernous tissue was performed. RESULTS: in this model of bilateral CN crush the treatment with implanted bioactive fibrous membrane induces CN regeneration and restoration of erectile function (p <0.001) (figure), showing a significant increased number of smooth muscle cells and nNOS and eNOS contents. Additionally, the bioactive fibrous membrane promotes a CN protective effect and increase the nerve regeneration capacity by increasing the number of myelinated axons and nNOS-positive cells, recovering from the CN fibrosis observed in rats not treated. CONCLUSIONS: This personalized regenerative strategy could help better recovery of erectile function after CN injuries, and it may constitute an effective novel option to prostate cancer patients suffering from ED after being subject to radical prostatectomy. Source of Funding: The authors would like to acknowledge the Portuguese Foundation for Science and Technology (FCT) for the PhD grant of M.R.C. (PD/BD/113797/2015) financed by the Doctoral Program on Advanced Therapies for Health (PATH) (FSE/POCH/PD/169/2013), the IF grant of A.M. (IF/00376/2014), the project Cells4_IDs (PTDC/BTM-SAL/28882/2017) and FCT - Portuguese Foundation for Science and Technology, under the project UIDB/04033/2020 © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e618 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Paulo Mota More articles by this author Marta Casanova More articles by this author Helena Vala More articles by this author Carmen Nóbrega More articles by this author Alain Morais More articles by this author Catarina Silva More articles by this author Sara Anacleto More articles by this author Alexandre Barros More articles by this author Rui Reis More articles by this author Estêvão Lima More articles by this author Albino Martins More articles by this author Nuno Neves More articles by this author Expand All Advertisement PDF DownloadLoading ...

Tumor Necrosis Factor- α (TNF-α) and Rho-Associated Kinase 2 (ROCK2) Inhibitors Improve Erectile Function in a Bilateral Cavernous Nerve Injury Rat Model

ABSTRACT Introduction Prior studies suggest Rho-kinase (ROCK) upregulation and pro-inflammatory cytokines such as Tumor Necrosis Factor-α as causative factors of axonal degeneration, neuropathy, and penile fibrosis following peripheral cavernous nerve (CN) injury. We hypothesize, the combination therapy using inhibitors/antagonists of ROCK and TNF-α may prevent end-organ damage and neuroinflammation in the penis. The current study was designed to investigate selective inhibition of ROCK2 (SAR407899) and TNF-α (Infliximab) in a pre-clinical model of post-radical prostatectomy ED to prevent penile neuroinflammation, fibrosis, and preserve penile hemodynamics. Objective This study investigates the effect of FDA approved TNF- α inhibitor (Infliximab) in combination with ROCK2 selective inhibitor (SAR407899) on erectile function restoration in the bilateral crush nerve injury (BCNI) rat model. Methods Sprague Dawley rats were randomized to undergo either sham (6) or BCNI (28). The BCNI rats were further randomly stratified to receive saline (6), Infliximab (5 mg/kg once weekly) (6), low dose of SAR407899 (1.5 mg/kg QD) (5), high dose of SAR407899 (3 mg/kg QD) (5), or combination treatment SAR407899 (1.5 mg/kg QD) + Infliximab (5 mg/kg once weekly) (6). At 14 days after injury rats underwent cavernous nerve stimulation to determine erectile function. Penes were collected and immune infiltrate analyses were performed using multicolor flow-cytometry. Results Erectile response studies demonstrated that rodents treated with combination of Infliximab and SAR407899 had significantly improved (p&amp;lt;0.05) erectile function (ICP/MAP) at all voltages compared to BCNI alone (2V: 0.243 vs 0.051, 4V: 0.321 vs 0.0782, 6V: 0.456 vs 0.091, p &amp;lt;0.05). Peak ICP and total ICP were also significantly (p&amp;lt;0.05) improved compared to BCNI rats. Combination therapy, however, did not show a significant change compared to each treatment alone. Likewise, there was no significant difference between low and high dose SAR407899. Flow cytometry showed that Infliximab and SAR407899 significantly (p&amp;lt;0.05) decreased % of CD11b+ CD45+ monocytes in the penis. While combination therapy had no effect. The percent of CD11b+ MHCII+ CD45+ macrophages were increased (p&amp;lt;0.05) in the penes of rats treated with Infliximab and SAR407899 while combination therapy decreased penile macrophage population. We found no change in TNF- α+ monocytes and macrophages compared in penes from all groups investigated. Conclusions Our study suggests that treatment with commercially available TNF-α and ROCK2 inhibitors result in mitigation of erectile dysfunction in a BCNI rat model when administered at the time of nerve injury. The mechanism of the beneficial effects may involve reduction in macrophage population in the penis. Disclosure No

Heat Shock Protein 70 in Penile Neurovascular Regeneration Requires Cystathionine Gamma-Lyase.

PurposeDiabetes mellitus, one of the major causes of erectile dysfunction, leads to a poor response to phosphodiesterase-5 inhibitors. Heat shock protein 70 (Hsp70), a ubiquitous molecular chaperone, is known to play a role in cell survival and neuroprotection. Here, we aimed to assess whether and how Hsp70 improves erectile function in diabetic mice.Materials and MethodsEight-week-old male C57BL/6 mice and Hsp70-Tg mice were used in this study. We injected Hsp70 protein into the penis of streptozotocin (STZ)-induced diabetic mice. Detailed mechanisms were evaluated in WT or Hsp70-Tg mice under normal and diabetic conditions. Primary MCECs, and MPG and DRG tissues were cultivated under normal-glucose and high-glucose conditions.ResultsUsing Hsp70-Tg mice or Hsp70 protein administration, we demonstrate that elevated levels of Hsp70 restores erectile function in diabetic mice. We found that cystathionine gamma-lyase (Cse) is a novel target of Hsp70 in this process, showing that Hsp70-Cse acts through the SDF1/HO-1/PI3K/Akt/eNOS/NF-κB p65 pathway to exert its neurovascular regeneration-promoting effects. Coimmunoprecipitation and pull-down assays using mouse cavernous endothelial cells treated with Hsp70 demonstrated physical interactions between Hsp70 and Cse with a dissociation constant of 1.8 nmol/L.ConclusionsOur findings provide novel and solid evidence that Hsp70 acts through a Cse-dependent mechanism to mediate neurovascular regeneration and restoration of erectile function under diabetic conditions.

Directions of Development of Modern Genital Surgery. Features, Details, Nuances

The quality of life and self-esteem of a modern man are largely determined by the appearance and functional state of his genitals. The quite high demand for improving the morpho-functional properties of the penis is the driving force of progress in the field of penile surgery. Despite the positive meaning of the surgical arsenal diversity for meeting the needs of the patient, the latter puts additional requirements for standardization, safety assessment and development of algorithms for their selection. Under these circumstances, there is a significant need for publications that inform specialist with the practical aspects of external genital surgery in men. The objective: to analyze modern algorithms for managing patients with various pathologies / defects of the penis (penile dysmorphophobia, erectile dysfunction, Peyronie’s disease, congenital deviation, priapism, cavernous fibrosis, trauma and tumors) and methods of their surgery. Materials and methods. Bibliosemantic material that covers current aspects and trends of genital surgery over the past 10 years, and case reports of patients who applied to the Department of Sexopathology and Andrology of the Institute of Urology of the National Academy of Medical Sciences of Ukraine with penile pathology that required surgical correction. Results. It is demonstrated that the algorithm of managing a patient with anatomical defects of the penis, should include: analysis and correction of deformation based on geometric principles; increase in size and / or elongation of the short side (small curvature); minimization of complications (loss of sensitivity, hematoma, necrosis); preservation or restoration of erectile function; restoration of the urethra (length and caliber), normalization of the urination, restoration of a full sexual life with adequate psychological adaptation. It has been shown that severe erectile dysfunction, which is not amenable to therapeutic correction, requires the penile implantation. On the other hand, penile implantation is contraindicated in uncompensated diabetes mellitus, decompensation of the cardiovascular system, late-stage cancer, acute inflammatory processes of various localizations, mental illness, skin lesions of various etiologies in the area of the scrotum and penis, in patients with a high frequency of repeated endoscopic procedures, tissue defects in the area of operation with the predicted inability to stretch, hypersensitivity to silicone, the mismatch of the size of the corpora cavernosa to the size of the selected type of implant. It has been proven that ligamentotomy and corporoplasty prevent the loss of penis length after implantation, but increase the likelihood of complications. Complications of penile implantation include: prosthesis-associated infection, erosions, migration or extrusion of the prosthesis, migration of proximal tips, mechanical failure of the prosthesis, tissue and / or allergic reaction, acute urinary retention, pain, hematoma, edema, edema and lymphoma intraoperative perforation of the urethra or corpora cavernosa. Clinical cases of certain complications and methods of their elimination are given. The choice of method of correction of penile deviation is determined by the state of erectile function, the length of the penis, the angle of curvature, the wishes of the patient. Grafting (short penis, angle of curvature&gt; 60 °, presence of deformities) or plication (sufficient length of the penis, angle of curvature &lt;60 °, no deformities) can be performed if erectile function or pharmacotherapy is preserved. At erectile dysfunction at condition of inefficiency of pharmacotherapy implantation is shown. Conclusion. At the present stage, the main direction of movement in genital surgery is a combination of aesthetics and functionality. A specialist in penile surgery must have the skills of a urologist, andrologist, aesthetic surgeon and psychologist. In patients with penile dysmorphophobia, subjective assessment of the appearance of the genitals correlates with psychological status. The main psychological feature of a patient with penile dysmorphophobia is dissatisfaction with the size of the penis (length and / or thickness) at normal anatomical proportions. The modern arsenal of penile surgery is diverse and includes methods of correction of deviations / deformations, increase in size (length / thickness); axial rigidity, urethral capacity (length and caliber), during which implants can be used. Penile surgery is associated with the risk of severe complications: loss of sensitivity of the penile glans, hematoma, necrosis, prosthetic infection, rupture of the the corpora cavernosa and urethra. Further research should determine optimal algorithms for selecting certain surgical techniques taking into account aesthetic, functional criteria and safety.

Combination Therapy with a JNK Inhibitor and Hepatocyte Growth Factor for Restoration of Erectile Function in a Rat Model of Cavernosal Nerve Injury: Comparison with a JNK Inhibitor Alone or Hepatocyte Growth Factor Alone

We determined if combined administration of JNK-inhibitors and HGF (hepatocyte-growth-factor) would restore erectile-function through both antiapoptotic and regenerative effects in a rat model of cavernous-nerve-crush-injury (CNCI), and compared the results with administration of JNK-inhibitor alone or HGF alone. We randomized 70 rats into 5 groups: sham-surgery-group (S), CNCI (I) group, a group treated with once-daily intraperitoneal-administration of 10.0-mg/kg of JNK-inhibitors (J), a twice-weekly intracavernosal-administration of 4.2-μg HGF group (H), and a combined-treatment with 10.0-mg/kg JNK-inhibitors and 4.2-μg HGF group (J+H). We investigated erectile-responses to electrostimulation, histological-staining, caspase-3-activity-assay, and immunoblotting at two-weeks postoperatively. The three treatment groups showed improvements in erectile-responses (ICP/MAP and AUC/MAP ratios) compared to Group-I. The erectile-responses in Group-J+H were greater than those in Group-J or Group-H. The erectile-responses in Group-J+H were generally normalized. Caspase-3-activity and cJun-phosphorylation in Group-J and Group-J+H improved compared to Group-I, whereas caspase-3-activity in Group-H partially improved. Protein-expression of PECAM-1, eNOS-phosphorylation, and smooth-muscle content in Group-J+H were normalized, although those in Group-J or Group-H were partially restored. Combination therapy with JNK-inhibitors and HGF can generally normalize erectile-function through anti-apoptosis and preservation of endothelium or SM in rat CNCI model. The combined treatment appears to be superior to the respective agent alone in terms of therapeutic effects.

Restoration of erectile function by a combination of antiapoptosis by JNK inhibitor and preservation of smooth muscle or endothelium by hepatocyte growth factor in a rat model of cavernous nerve injury

Because of structural alterations in the corpus cavernosum after radical prostatectomy (RP), post-RP erectile dysfunction remains a very difficult condition to treat. We aimed to determine if the combined administration of a Jun-amino terminal kinase (JNK) inhibitor and hepatocyte growth factor (HGF) in the immediate post-injury period would restore erectile function by antiapoptotic and pro-regenerative effects through the rectification of molecular pathways related to the structural integrity of the penis in a rat model of bilateral cavernosal nerve crush injury (CNCI). A total of 70 rats were divided into five groups: Sham surgery (S), CNCI (I), and once-daily intraperitoneal administration of 10.0 mg/kg JNK inhibitor + twice-weekly intracavernosal administration of low-dose (2.1 μg), medium-dose (4.2 μg), or high-dose (8.4 μg) HGF (I + J + LH or I + J + MH or I + J + HH, respectively) in the immediate post-injury period. Erectile responses to electrostimulation (1.0, 3.0, and 5.0 V), histological staining, caspase-3 activity, and Western blotting were evaluated 9 days after surgery. Group I showed lower intracavernosal pressure (ICP)/mean arterial pressure (MAP) after stimulation at each voltage, lower area under the curve (AUC)/MAP after stimulation at each voltage, less smooth muscle (SM) content, a lower SM/collagen ratio, higher caspase-3 activity, increased cJun phosphorylation, decreased protein expression of PECAM-1, decreased cMet phosphorylation, and decreased endothelial nitric oxide synthase(eNOS) phosphorylation compared to Group S. The SM content, SM/collagen ratio, protein expression of ICP/MAP, or AUC/MAP after stimulation at each voltage in Group I + J + LH were partially restored, despite the normalization of cJun phosphorylation and caspase-3 activity. The ICP/MAP, AUC/MAP, caspase-3 activity, SM content, protein expression of PECAM-1, cJun phosphorylation, cMet phosphorylation, and eNOS phosphorylation in both Groups I + J + MH and I + J + HH were restored to the levels observed in Group S, while the SM/collagen ratio was significantly improved but not completely normalized. Our data indicated that the combined administration of a JNK inhibitor and medium or high-dose HGF to nerve-injured rats in the immediate post-injury period after CNCI may restore erectile function to a level comparable to the normal level by suppressing cavernosal apoptosis and preserving the integrity of SM or endothelium via rectification of the cJun and cMet/eNOS pathways.

Restoration of erectile function in men after prostate surgery in the immediate postoperative period: the needs assessment for patients and their partners to maintain sexual relations

Introduction. Despite the advances in the modern pharmacopoeia, a significant place is given to surgical methods of treating benign prostatic hyperplasia (BPH) and prostate cancer (PCa). In the postoperative period in men, sexual function usually deteriorates.Purpose of the study. To study the needs of men after prostate surgery and their sexual partners in restoring their previous sexual life.Materials and methods. The pilot open-label prospective randomized non-comparative study included 50 patients in the age range of 53 – 74 years (average 58.3 years). All patients were consistently admitted and operated on at the “Avicenna” Medical Centre, Ltd. (Novosibirsk) from January to December 2020. Upon admission, all patients completed the International Index of Erectile Function (ICEF) questionnaire; one month later, this questionnaire was re-completed, supplemented with five questions.Results. Twenty-one patients were admitted with a diagnosis of PCa T1c – T2N0M0, all of them underwent laparoscopic prostatectomy with lymphadenectomy. Twenty-nine patients were operated on for BPH. They underwent transurethral resection with a bipolar resectoscope. Only 6 patients (12%) had no comorbidities. Surgical intervention worsened sexual function in all patients, while in men aged 50 – 59 years, the IIEF score decreased by 61.0%, at the age of 60 – 69 years by 39.0%, in patients over 70 years old by 55.2%. Eighteen (36.0%) patients showed interest in restoring sexual function. Thirty-two (64%) patients were against the continuation of sexual activity with the following motivation: 19 (59.4%) – lack of desire for a sexual partner, 8 (25.0%) – lack of desire of the patient himself, 5 (15.6%) – unwillingness to re-operated. Nineteen women out of 36 stable couples (52.8%) objected to the restoration of the sexual function of their sexual partners.Conclusion. Prostate surgery affects male sexual function more severely in younger patients. Thirty-two patients after surgery refused to restore sexual activity, in more than half of cases (59.4%) due to the unwillingness of the sexual partner to resume sexual relations.

The genitofemoral and ilioinguinal nerves as neurorrhaphy candidates for erectile function restoration in patients with prostatectomy-induced erectile dysfunction

The genitofemoral and ilioinguinal nerves as neurorrhaphy candidates for erectile function restoration in patients with prostatectomy-induced erectile dysfunction

PD62-07 TUMOR NECROSIS FACTOR ALPHA (TNF- Α) INHIBITOR IMPROVED ERECTILE FUNCTION IN A BILATERAL CAVERNOUS NERVE INJURY RAT MODEL

You have accessJournal of UrologySexual Function/Dysfunction: Basic Research & Pathophysiology (PD62)1 Sep 2021PD62-07 TUMOR NECROSIS FACTOR ALPHA (TNF- Α) INHIBITOR IMPROVED ERECTILE FUNCTION IN A BILATERAL CAVERNOUS NERVE INJURY RAT MODEL James Liu, Hotaka Matsui, Kara Lombardo, Serkan Karakus, Arthur Burnett, and Trinity Bivalacqua James LiuJames Liu More articles by this author , Hotaka MatsuiHotaka Matsui More articles by this author , Kara LombardoKara Lombardo More articles by this author , Serkan KarakusSerkan Karakus More articles by this author , Arthur BurnettArthur Burnett More articles by this author , and Trinity BivalacquaTrinity Bivalacqua More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002099.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Erectile dysfunction (ED) after injury to the peripheral cavernous nerves (CN) is partially the result of an increase in neuroinflammation in the pelvic ganglia. Inflammatory cytokines have been implicated in axonal degeneration and neuropathy. This study examines the role of the inflammatory cytokine, tumor necrosis factor –alpha (TNF- α), after bilateral CN injury (BCNI) in vivo. We also investigate the effect of commercially available TNF- α inhibitors (Infliximab) on erectile function restoration in the BCNI rodent model. METHODS: Seventy male Sprague Dawley rats were randomized to undergo either BCNI or sham surgery. Sham rats major pelvic ganglion (MPG) were harvested after 48 hours, whereas the BCNI groups had MPG harvested at 6 hours, 12 hours, 24 hours, 48 hours, 7 days, or 14 days after BCNI. MPGs were analyzed by qPCR to evaluate gene expression of TNF-α, TNF- αR1, TNF- αR2 and markers of macrophages (CD11b and CD68). Western blot of MPGs were also performed to confirm these finding. Additionally, 25 Sprague Dawley rats were randomized to three groups: sham surgery, BCNI, or BCNI treated with TNF- α inhibitor (Infliximab) (5mg/kg weekly) for two weeks and then underwent cavernous nerve stimulation and erectile parameters were measured (peak ICP, ICP/MAP, and total ICP). RESULTS: BCNI significantly increased (p<0.05) gene and protein expression of TNF- α and its receptors (R1, R2) in rat MPGS, with peak levels were observed at 2 and 7 days, respectively. Corresponding macrophage markers (CD11b and CD68) were significantly increased (p<0.05) following BCNI with maximal expression at 48 hours. Erectile response studies demonstrated that rodents treated with TNF- α inhibitors had significantly improved (p<0.05) erectile function (ICP/MAP) at all voltages compared to BCNI alone (2V: 0.203 vs 0.057, 4V: 0.279 vs 0.081, 6V: 0.317 vs 0.166. Control 2V: 0.347, 4V: 0.414, 6V: 0.486). Peak ICP and total ICP were also significantly (p<0.05) improved compared to BCNI rats. CONCLUSIONS: TNF- α is a key inflammatory cytokine which contributes to neuroinflammation following BCNI. Treatment with commercially available TNF- α inhibitor results in mitigation of erectile dysfunction in a BCNI rat model when administered at the time of nerve injury. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1074-e1075 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information James Liu More articles by this author Hotaka Matsui More articles by this author Kara Lombardo More articles by this author Serkan Karakus More articles by this author Arthur Burnett More articles by this author Trinity Bivalacqua More articles by this author Expand All Advertisement Loading ...

P0475 - Strategy for the restoration of erectile function by a combination of anti-apoptotic effects by a JNK inhibitor and regeneration by hepatocyte growth factor in a rat model of cavernosal nerve injury

P0475 - Strategy for the restoration of erectile function by a combination of anti-apoptotic effects by a JNK inhibitor and regeneration by hepatocyte growth factor in a rat model of cavernosal nerve injury

Целесообразность и риски применения нервосберегающей техники радикальной простатэктомии в отношении пациентов старшей возрастной группы

OBJECTIVE To evaluate the efficacy and safety of radical prostatectomy (RP) with nerve-saving technique (NST) in patients more or equal 65 years of age compared with a younger group of patients. MATERIALS AND METHODS The study group comprised 117 patients more or equal 65 years old, the control group - 333 patients <65 years old, who underwent RP with unilateral or bilateral NST from January 2012 to December 2019. The analysis of pathomorphological results, complications rate, recurrence free survival (RFS) and the restoration of erectile function (EF) in both groups was performed. RESULTS The majority of older patients belonged to intermediate and high risk groups of biochemical recurrence. Extracapsular tumor extension was significantly more often observed in the group more or equal 65 years of age: 16.2% and 6.9%, p=0.028. There were no differences between the two groups in the frequency of serious postoperative complications ( more or equal III class according to the Clavien-Dindo classification): 2.55% and 2.7%; p=0.94. The five-year RFS after RP was 95.4% in the group <65 years old and 92.1% in the group more or equal 65 years old (p=0.31). There was a moderate tendency to a slower recovery of EF in older patients: sufficient EF after 6 and 12 months was observed in 21.9% and 59.4% versus 33.3% and 73% in the group <65 years old (p=0.12). Minimal differences in EF were observed 24 months after RP with bilateral NST (84.2% and 87.9%), and more relevant differences with unilateral NST: 53.8% and 66.7% in the study and control group (p=0.033). CONCLUSIONS The performance of RP with NST in elderly patients is not associated with additional oncological risks, while the restoration of EF is somewhat slowed down in comparison with a group of patients <65 years of age. Bilateral NST provides high potency recovery results regardless of age.

Vasohibin-1 rescues erectile function through up-regulation of angiogenic factors in the diabetic mice

Neovascularization of the erectile tissue emerges as a beneficial curative approach to treat erectile dysfunction (ED). Here we for the first time report the unexpected role of vasohibin-1 (VASH1), mainly known as an anti-angiogenic factor, in restoring erectile function in diabetic mice. A diabetic patient has lower cavernous VASH1 expression than in the potent man. VASH1 was mainly expressed in endothelial cells. There were significant decreases in cavernous endothelial cell and pericyte contents in VASH1 knockout mice compared with those in wild-type mice, which resulted in impairments in erectile function. Intracavernous injection of VASH1 protein successfully restored erectile function in the diabetic mice (~ 90% of control values). VASH1 protein reinstated endothelial cells, pericytes, and endothelial cell–cell junction proteins and induced phosphorylation of eNOS (Ser1177) in the diabetic mice. The induction of angiogenic factors, such as angiopoietin-1 and vascular endothelial growth factor, is responsible for cavernous angiogenesis and the restoration of erectile function mediated by VASH1. Altogether, these findings suggest that VASH1 is proangiogenic in diabetic penis and is a new potential target for diabetic ED.