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The mechanisms of adenosine and specific adenosine receptor subtypes in promoting penile rehabilitation remain unclear. Single‐cell RNA sequencing of human corpus cavernosum, adenosine deaminase (ADA) and adenosine receptors knock‐out mice (ADA−/−, A1−/−, A2a−/−, A2b−/−, and A3−/−), and primary corpus cavernosum smooth muscle cells are used to determine receptor subtypes responsible for adenosine‐induced erection. Three rat models are established to characterize refractory erectile dysfunction (ED): age‐related ED, bilateral cavernous nerve crush related ED (BCNC), and diabetes mellitus‐induced ED. In single‐cell RNA sequencing data, the corpus cavernosum of ED patients show a decrease in adenosine A1, A2a and A2b receptors. In vivo, A2b receptor knock‐out abolishes adenosine‐induced erection but not that of A1, A2a, or A3 receptor. Under hypoxic conditions in vitro, activating the A2b receptor increases HIF‐1α and decreases PDE5 expression. In refractory ED models, activating the A2b receptor with Bay 60–6583 improves erectile function and down‐regulates HIF‐1α and TGF‐β. Administering Dipyridamole (40 mg Kg−1) to BCNC rats improve penile adenosine levels and erectile function. Our study reveals that the A2b receptor mediates adenosine‐induced penile erection. Activating the A2b receptor promotes penile rehabilitation of refractory ED by alleviating hypoxia and fibrosis. [ABSTRACT FROM AUTHOR]

The article discusses the implementation of a 'Supported-at-Home' video tuition program for patients self-administering intracavernosal alprostadil injections for erectile dysfunction. The study aimed to assess the safety, efficacy, and acceptability of this method. Results showed that the video instructions were clear and useful, with most patients finding the self-administration process easy. The study concluded that the 'Supported-at-Home' approach is safe, effective, and acceptable, potentially increasing clinic productivity when used alongside traditional face-to-face appointments. [Extracted from the article]

Abstract The mechanisms of adenosine and specific adenosine receptor subtypes in promoting penile rehabilitation remain unclear. Single‐cell RNA sequencing of human corpus cavernosum, adenosine deaminase (ADA) and adenosine receptors knock‐out mice (ADA−/−, A1−/−, A2a−/−, A2b−/−, and A3−/−), and primary corpus cavernosum smooth muscle cells are used to determine receptor subtypes responsible for adenosine‐induced erection. Three rat models are established to characterize refractory erectile dysfunction (ED): age‐related ED, bilateral cavernous nerve crush related ED (BCNC), and diabetes mellitus‐induced ED. In single‐cell RNA sequencing data, the corpus cavernosum of ED patients show a decrease in adenosine A1, A2a and A2b receptors. In vivo, A2b receptor knock‐out abolishes adenosine‐induced erection but not that of A1, A2a, or A3 receptor. Under hypoxic conditions in vitro, activating the A2b receptor increases HIF‐1α and decreases PDE5 expression. In refractory ED models, activating the A2b receptor with Bay 60–6583 improves erectile function and down‐regulates HIF‐1α and TGF‐β. Administering Dipyridamole (40 mg Kg−1) to BCNC rats improve penile adenosine levels and erectile function. Our study reveals that the A2b receptor mediates adenosine‐induced penile erection. Activating the A2b receptor promotes penile rehabilitation of refractory ED by alleviating hypoxia and fibrosis.

Background: Phosphodiesterase type 5 (PDE5) inhibitor labeling states that these agents should not be used in conjunction with other erectogenic medications for fear of priapism occurring. Aim: We explored the risk of priapism and prolonged erections in men in our post–radical prostatectomy (RP) penile injection program who were using regular PDE5 inhibitor and intracavernosal injections (ICIs) as part of their rehabilitation program. Methods: The study cohort included men on penile injection therapy who (1) were taking tadalafil 5 mg daily or taking sildenafil 25 mg on noninjection days, (2) had an RP, (3) were using their respective PDE5 inhibitor regularly at the time of penile injection training, and (4) complied with the program instructions regarding penile injection use. Demographics, comorbidity details, PDE5 inhibitor dose and utilization, and injection dose and utilization data were collected. All patients underwent in-office injection training and used trimix (papaverine/phentolamine/prostaglandin E1) as the intracavernosal medication. Outcomes: Priapism was defined as a patient self-reported penetration hardness erection ≥4 hours in duration, while prolonged erection was defined as a penetration hardness erection lasting ≥2 hours. Results: A total of 112 tadalafil users and 364 sildenafil users were compared. Mean age and duration post-RP were 62 ± 14 years and 5.2 ± 12 months, respectively, and there was no difference between tadalafil and sildenafil groups. The mean trimix dose was tadalafil 24 ± 24 units and sildenafil 31 ± 37 units (P < .05). Priapism occurred in 2 (1.7%) of 112 tadalafil users and 5 (1.4%) of 364 sildenafil users (P = .47). Excluding those men experiencing priapism on any occasion, those with any reported penetration hardness erection lasting ≥2 hours were 7 (6.3%) of 112 tadalafil users and 12 (3.3%) of 364 sildenafil users (P < .01). A total of 53% of these prolonged erections occurred within the first 6 injections at home (no difference between tadalafil and sildenafil groups). Clinical Implications: We emphasize the need for continued monitoring and education on proper injection techniques to minimize the risk of adverse events in ICI and PDE5 inhibitor combination therapy. Strengths & Limitations: This study has a relatively large patient population with a considerable follow-up time. Additionally, the rigorous training, education, and monitoring of the participants, as well as the use of formal definitions for priapism and prolonged erections, enhances the accuracy and reliability of the results. However, there are some limitations, such as social desirability, confounding factors, and recall bias. Conclusion: There is no significant difference in the incidence of priapism in an ICI program in which men combine ICI with tadalafil or sildenafil. However, tadalafil patients had a higher rate of prolonged erections, which was found to occur mostly early during the titration phase. [ABSTRACT FROM AUTHOR]

There have been considerable advances in the field of penile rehabilitation for upwards of 90% of men adversely affected by either short-term or long-term erectile dysfunction after definitive prostate cancer treatment. Despite the evolving landscape of treatment modalities for penile rehabilitation, there is a lack of consensus in the urologic community on the best therapies due to the level of evidence and efficacies of the current and emerging offerings. This review of current and next-generation interventions provides a practical approach to the myriad of data to make a better-informed decision based on the pathophysiology and highest-quality evidence available.

Peyronie's disease (PD) is an acquired disease, which is based on a violation of the wound healing process, which results in the formation of fibrous plaques in the tunica albuginea of the cavernous bodies. The prevalence of erectile dysfunction (ED) among patients with PD ranges from 22% to 54%, according to various studies. Surgical treatment remains the "gold standard" for correcting penile curvature in PD. It is important to note that the existing methods of PD surgery (techniques with shortening or lengthening of the tunica albuginea) carry the risks of developing ED or aggravating its severity. At the same time, the absence of adequate sexual rehabilitation following PD surgery is associated with a significant deterioration in functional outcomes. In view of the above, the article is aimed to systematise information on penile rehabilitation methods in patients following PD surgery, which showed that the problem remains relevant to the present day. Most existing penile rehabilitation methods are currently not sufficiently investigated, and it is therefore impossible to give clear recommendations on the use of any method. The small number of well-designed and randomised studies on this problem is noteworthy, most likely due to the relative rarity of the disease.

The prevalence and incidence of malignancies in the Czech Republic is increasing. Advances in the diagnosis and treatment modalities applied in the field of oncology during the last decade have led to an increase in the overall survival of patients with many different types of tumors. As a result, maintaining quality of life is another important issue for oncology patients. Sexual problems in oncology patients can stem from impairment of libido, arousal, orgasm and ejaculation, sexual satisfaction and pain. Prostate, bladder and colorectal cancer are the most common malignancies that are diagnosed in middle-aged men who do not renounce their sexuality after undergoing treatment. The consultation with the patient before starting complex treatment should therefore include familiarization with the risk of sexual dysfunctions, treatment modalities and the possibility of penile rehabilitation. [ABSTRACT FROM AUTHOR]

Erectile dysfunction (ED) caused by cavernous nerve injury (CNI) is refractory to heal mainly ascribed to the adverse remodeling of the penis induced by ineffectual microvascular perfusion, fibrosis, and neurotrophins scarcity in cavernosum. Phosphodiesterase type V inhibitors (PDE5i) have been regarded as an alternative candidate drug for avoiding penile neuropathy. However, the therapeutic efficacy is severely limited due to poor accumulation under systemic medication and endogenous nitric oxide (NO) deficiency in cavernosum. Herein, an innovative liposomal microbubble (MB) loaded with both Sildenafil (one of PDE5i) and NO was designed. Ultrasound‐targeted MB destruction (UTMD)‐mediated efficient release and integration erectogenic agents into corpus cavernosum with high biosafety. On a bilateral CNI rat model, the multifunctional MB‐cooperated UTMD improved microvascular perfusion in penis, simultaneously, alleviated hypoxia and oxidative stress, indicating successful activation of NO–cyclic guanosine monophosphate pathway. Also, evaluation of the endothelial/muscular composition, intracavernosal pressure, and neural integrity in the penis proved that coordinated intervention reversed the abnormal structural remodeling and promoted the recovery of functional erection. Our work demonstrates that MB loading Sildenafil and NO combined with UTMD hold great promise to "awaken" the efficacy of PDE5i in neurogenic ED, which provided a superior option for ensuring penile rehabilitation. [ABSTRACT FROM AUTHOR]

Pelvic malignancies, including prostate, rectal, and bladder cancers, are among the most frequent malignancies found in the male population. These issues are most effectively and commonly treated with radiotherapy and/or surgery. However, these treatments can cause collateral damage, resulting in significant impacts on quality of life, with erectile dysfunction being one of the most frequent postoperative complications. Currently, there are several treatment options for erectile dysfunction, including oral phosphodiesterase type 5 inhibitors, vacuum erection devices, intracorporeal injections, and penile prosthesis. The latter has shown to be an effective and safe technique, with results comparable to those obtained by patients without pelvic surgery or radiotherapy. The results of early penile rehabilitation programs are promising and they have been incorporated into a greater proportion of treatment plans more recently, with varying degrees of success. In this narrative review, we summarize the literature on erectile dysfunction after pelvic cancer treatments and its management. [ABSTRACT FROM AUTHOR]

Abstract Erectile dysfunction (ED) caused by cavernous nerve injury (CNI) is refractory to heal mainly ascribed to the adverse remodeling of the penis induced by ineffectual microvascular perfusion, fibrosis, and neurotrophins scarcity in cavernosum. Phosphodiesterase type V inhibitors (PDE5i) have been regarded as an alternative candidate drug for avoiding penile neuropathy. However, the therapeutic efficacy is severely limited due to poor accumulation under systemic medication and endogenous nitric oxide (NO) deficiency in cavernosum. Herein, an innovative liposomal microbubble (MB) loaded with both Sildenafil (one of PDE5i) and NO was designed. Ultrasound‐targeted MB destruction (UTMD)‐mediated efficient release and integration erectogenic agents into corpus cavernosum with high biosafety. On a bilateral CNI rat model, the multifunctional MB‐cooperated UTMD improved microvascular perfusion in penis, simultaneously, alleviated hypoxia and oxidative stress, indicating successful activation of NO–cyclic guanosine monophosphate pathway. Also, evaluation of the endothelial/muscular composition, intracavernosal pressure, and neural integrity in the penis proved that coordinated intervention reversed the abnormal structural remodeling and promoted the recovery of functional erection. Our work demonstrates that MB loading Sildenafil and NO combined with UTMD hold great promise to “awaken” the efficacy of PDE5i in neurogenic ED, which provided a superior option for ensuring penile rehabilitation.

The management of sexual complications after treatment of localized prostate cancer, such as erectile dysfunction, changes in the length of the penis, pain during sexual intercourse, and lack of orgasm, is still an unsolved problem with an important impact on patients' quality of life. In this review, we summarize the current scientific literature about the rehabilitation of erectile dysfunction after prostate cancer treatment. The therapy for penile rehabilitation includes different types of treatments: the combination of phosphodiesterase type 5 inhibitors (PDE5-I) and the vacuum erectile device (VED) are considered first-line treatment options. When therapy begins, the duration of treatment, the dosage and the drug used all play very important roles in the treatment outcome. Intracavernous injection (ICI) therapy represents the second-line option for patients ineligible for PDE5-I therapy. Technological development has led to the emergence of devices for the stimulation of the penis without the use of drugs, such as penile vibratory stimulation (PVS) for stimulation of ejaculation in spinal cord injury and low-intensity extracorporeal shockwave therapy (LIESWT). The rapid diffusion of the latter, thanks to its easy use, attains good results without side effects. The panorama of penile rehabilitation after PC treatments is vast and many studies are needed, especially on new technologies, to find the best therapeutic regimen possible, personalized to the patient's characteristics and the type of treatment for PC. [ABSTRACT FROM AUTHOR]

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

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Introduction: The objective of this study was to investigate the effect and feasibility of linear low-intensity extracorporeal shockwave therapy (LI-LiESWT) as a penile rehabilitation method for erectile dysfunction (ED) after bilateral nerve-sparing (NS) radical prostatectomy (RP). Methods: Patients who had undergone bilateral NS RP (either radical retropubic prostatectomy or robot-assisted laparoscopic RP), 3 or more months prior to the study, and who had no ED preoperatively and were suffering from mild to severe postoperative ED were included in the study. Four treatments were given over a 4-week period, using the PiezoWave2 device with a linear shockwave applicator and the linear shockwave tissue coverage (LSTC-ED®) technique. If the improvement in erectile function was still considered insufficient (less than an IIEF-5 score of 22–25) at 2 months after the start of LI-LiESWT, penile rehabilitation was supplemented by pharmacological penile rehabilitation. The final effect of treatment was evaluated after 12 months. The main outcome measure was changes in the five-item International Index of Erectile Function (IIEF-5) score. Results: Between September 2019 and September 2020, a total of 40 patients were included in the study and randomly divided into 2 groups: treatment group and sham group. Eight patients were excluded from the study and were not evaluated due to other conditions which required additional treatment (COVID-19 disease, postoperative incontinence, urethral stricture, and ischemic stroke). Thirty-two patients were included in the final analysis: 16 in the control group and 16 in the intervention group. At 6 months from the end of treatment, patients in both the treatment and the sham group achieved physiological IIEF-5 values, and the beneficial effect persisted for 12 months after the end of treatment. Conclusions: LI-LiESWT using the LSTC-ED® technique is a suitable and safe method for penile rehabilitation in patients with ED after bilateral NS RP, not only because of the vasculogenic effect of LI-LiESWT but also because of its neuroprotective and/or regenerative effects. [ABSTRACT FROM AUTHOR]

Purpose of Review: Although there have been advancements in minimally invasive surgical techniques for radical prostatectomy, surgery can still significantly impact continence and erectile function (EF), resulting in considerable quality-of-life impairment. This review critically evaluates existing treatment options for male stress urinary incontinence (SUI) and erectile dysfunction (ED) post-robotic-assisted laparoscopic prostatectomy (RALP), alongside exploring emerging trends and discussing future directions for managing and preventing both conditions., Recent Findings: Patient history is pivotal in guiding surgical decisions, with the intensity of symptoms and their impact on the patient's life being primary influences for deciding the best treatment options for both SUI and ED. Penile rehabilitation strategies (PR) show promise in mitigating the effects of prostate cancer treatments on EF and improving overall health, though consensus is lacking on specific programs or initiation of timing for optimal recovery post-surgery. All patients undergoing RALP should receive preoperative counseling about SUI and early pelvic floor physical therapy. Fixed and adjustable slings effectively treat mild-to-moderate post-RALP SUI, while the artificial urinary sphincter is the gold standard for men with moderate or severe SUI. EF recovery after RALP faces obstacles such as patient characteristics, compliance, and cost, with no standardized PR approach. Future research should prioritize studies aiming to optimize treatment methods and enhance patient compliance., Competing Interests: Declarations Human/Animal Studies Informed Consent Statement This article does not contain any studies with human or animal subjects performed by any of the authors. Competing Interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction. In healthy men, a significant increase in pO2 in the cavernous tissue occurs during episodes of nocturnal erections. This process ensures sufficient oxygenation and high-pressure substances such as prostaglandin-E1 and nitric oxide. These substances suppress the expression of transforming growth factor β1, thereby preventing collagen synthesis and the development of cavernous fibrosis. In patients undergoing nerve-sparing radical prostatectomy, nocturnal erections are absent, hypoxia inhibits the production of PGE-i, and neuropraxia inhibits NO. Thus, cavernous fibrosis develops through the production of pro-apoptotic and profibrotic factors, resulting in persistent erectile dysfunction. The importance of a vacuum in penile rehabilitation for the prevention of penile cavernous hypoxia is not fully understood. This is due to the deficiency of data on the gas composition of cavernous blood when a vacuum-induced erection is achieved.Purpose of the study. To investigate the cavernous blood at the time of vacuum-induced erection, to analyze the obtained results with the International Index of Erectile Function score and with the values of penile hemodynamics.Materials and methods. The study included i5 patients with prostate cancer and preserved sexual function. The average age of all men was 57.87 ±4.36 years. All patients underwent a preoperative comprehensive assessment of erectile function: International Index of Erectile Function questionnaire, dynamic duplex penile ultrasound. Immediately prior to the surgery, penile blood was collected at the time of achieving a vacuum-induced erection. The gas composition and oxygenation were assessed using the values of the partial oxygen pressure, carbon dioxide and saturation in accordance with the approved standards to differentiate arterial and venous blood. Statistical data processing was carried out using the PASW Statistics 22 software (IBM SPSS, IBM Corp., Chicago, IL, USA)Results. All patients were divided into 3 groups depending on the gas composition and oxygen level of the cavernous blood. Group I included 4 (26.6%) patients with a predominance of arterial blood, group II — 4 patients (26.6%) with venous blood and group III — 7 patients (46.6%) with a mixed composition of cavernous blood. The average International Index of Erectile Function score in group I was 23.5 [2i.0; 25.0], in group II — 22.0 [2i.0; 24.0] and in group III — 24.0 [i9.0; 25.0]. Peak systolic velocity (cm/s) in group I was 40.i [35.i; 45.2], in group II — 35.9 [29.5; 50.2], in group III — 32.5 [32.5; 34.4]. End-diastolic velocity (cm/s) in group I was 2.52 [0.55; i0.5], in group II — 8.3 [2.9; i0.8], in group III — 7.5 [7.5; 9.0]. Resistive index in group I was 0.87 [0.77; 0.98], in group II — 0.75 [0.63; 0.94], in group III — 0.75 [0.73; 0.75].Conclusions. Vacuum prophylaxis may be the method of choice for penile rehabilitation in patients after nerve-sparing radical prostateectomy, especially in the early postoperative period during neuropraxia. The use of vacuum devices should be prescribed to patients with preserved veno-occlusive mechanism, which should be confirmed by dynamic duplex penile ultrasound.

Objective: The aim of this study is to evaluate recovery of erectile function for penile rehabilitation following unilateral nerve sparing radical prostatectomy. Material and Methods: A total of 40 patients was recruited. The 40 patients were randomized to take Tadarafil on a regular basis (Rehabilitation group) or on demand (on demand group). Erection function questionnaires were used EPIC (Expanded Prostate Cancer Index Composite) and SHIM (Sexual Health Inventory for Men). Tadarafil was taken two times weekly. Results: Preoperative SHIM, EPIC sexual function (SF) and sexual bother (SB)score of the both groups were not statistically significant. Erectile function recovery cases were 15 cases (78%) in the Rehabilitation group and 10 cases (53%) in on demand group (p = 0.08). SB score at postoperative 6 months of the Rehabilitation group was significantly higher than that of the on demand group (p = 0.048). Conclusion: Penile rehabilitation shows effect for recovery of erectile function following unilateral nerve sparing radical prostatectomy. [ABSTRACT FROM AUTHOR]

Erectile dysfunction (ED) is a well-known complication of radical prostatectomy (RP). Oral 5-phosphodiesterase inhibitors are currently the most widely used penile rehabilitation treatment for ED following RP, but they are less effective than for those with general ED. Low-intensity extracorporeal shock wave treatment (LI-ESWT), causing a biological change that induces neovascularization, has recently been used as a treatment for ED. Therefore, we conducted a systematic review and meta-analysis to investigate the efficiency of LI-ESWT in ED following RP. PubMed, Embase, and the Cochrane Library were searched up until December 2021. The endpoint was the change in IIEF scores after LI-ESWT. Five papers (460 patients) were included in the final analysis. In IIEF scores performed 3–4 months after LI-ESWT, the group receiving LI-ESWT showed statistically significantly better results than the control (WMD = −2.04; 95% CI, −3.72 to −0.35; p = 0.02). However, there were a total of two studies that measured the results after 9–12 months. There was no statistical difference between the two groups (WMD = −5.37; 95% CI, −12.42 to 1.69; p = 0.14). The results of this analysis indicate that LI-ESWT showed a statistically significant effect on early recovery in penile rehabilitation of ED following RP. However, the level of evidence was low. Therefore, careful interpretation of the results is required. [ABSTRACT FROM AUTHOR]

Neurogenic erectile dysfunction (ED) following radical prostatectomy (RP) is a frequent complication often leading to erectile tissue remodeling and permanent ED. Low-intensity electrostimulation (LIES) has been shown to enhance peripheral nerve regeneration, however, its application on cavernous nerves (CN) has never been investigated. To investigate whether LIES enhances CN regeneration, improves erectile function (EF) recovery, and prevents corpora cavernosal remodeling after CN injury, which is a principal factor for ED following RP. Adult male Sprague-Dawley rats were divided into Sham, Bilateral Cavernous Nerve Injury (BCNI), and BCNI + LIES (1V, 0.1ms, 12Hz, 1h/day). After 7days, EF was assessed (ICP measurement). Penes and CN were collected for molecular analyses of TGF- β 1, Il-6, CRP, eNOS, ERK and AKT protein levels in corpus cavernosum (CC), and immunohistological analysis of DHE, total collagen and α-SMA in CC and S-100, Tub-III, DAPI, TUNEL, and nNOS in CN. Effects of LIES on EF, erectile tissue remodeling and CN structure. EF was decreased (P <.05) 7 days after BCNI and increased (P <.05) by LIES. Intracavernosal reactive oxygen species (DHE) was increased (P <.05) after BCNI and normalized by LIES. Protein expressions of TGF-β1, IL-6, and CRP were increased in the penis (P <.05) after BCNI and normalized by LIES. The α-SMA and/or total collagen ratio was decreased (P <.05) after BCNI in the penis and normalized by LIES. Protein expression ratio of p-ERK/ERK and p-AKT/AKT did not change after BCNI but increased (P <.05) in LIES group. Myelination and number of nNOS positive cells in the CN were decreased (P <.05) after BCNI and normalized by LIES. The number of apoptotic nerve cells within the dorsal penile nerve was increased (P <.05) after BCNI and decreased (P <.05) by LIES compared to the BCNI group. There were no differences in eNOS expression in the penis between study groups. LIES may offer a potential new tool for penile rehabilitation and ED management following RP, potentially enhancing EF recovery and minimizing the side effects of this surgery. This study provides evidence of the protective effect of LIES on EF and tissue remodeling following CN injury; nevertheless, this study has been conducted on animals and the translation to humans remains to be demonstrated. Further research to identify the underlying mechanisms of action is required. This study demonstrates that LIES of the CN after CN injury protects CN structure, enhances EF recovery, and prevents corpora cavernosal remodeling. Sturny M, Karakus S, Fraga-Silva R, et al. Low-Intensity Electrostimulation Enhances Neuroregeneration and Improves Erectile Function in a Rat Model of Cavernous Nerve Injury. J Sex Med 2022;19:686–696. [ABSTRACT FROM AUTHOR]

ABSTRACT: Background: Despite the widespread practice of nerve-sparing robot-assisted radical prostatectomy (nsRARP) for the treatment of localized prostate cancer (PCa), erectile dysfunction remains a significant sequela of radical prostatectomy. Aim: This study aimed to compare the efficacy of tadalafil 5 mg once daily for erectile function recovery in patients who underwent nsRARP according to the timing of rehabilitation initiation. Methods: In this double-blind, prospective pilot study, a total of 41 patients who underwent nsRARP were randomly assigned into 2 groups according to the timing of rehabilitation initiation. In the preRARP group (n = 20), tadalafil was started 2 weeks before nsRARP, and in the postRARP group (n = 21), it was started 4 weeks after nsRARP. Erectile function recovery after nsRARP was defined as an International Index of Erectile Function (IIEF-5) score of ≥17. Outcomes: The measures of EF recovery were the changes in IIEF-5 score. Results: The rate of erectile function recovery at 12-month follow-up was 80.0% and 71.4% in the preRARP and postRARP groups, respectively. The mean differences between baseline and postoperative IIEF-5 scores at 1-, 3-, 6-, and 12-month follow-up were −11.7 ± 3.2, −7.4 ± 3.2, −5.6 ± 1.5, and −4.1 ± 1.1 in the preRARP group and −14.7 ± 4.7, −12.0 ± 5.0, −9.7 ± 3.9, and −6.0 ± 3.1 in the postRARP group, respectively (1-month, P = .259; 3-months, P = .077; 6-months, P = .014; 12-months, P = .007). Clinical implications: Preoperative tadalafil 5 mg once a day could be used effectively and safely as a strategy for penile rehabilitation after nsRARP. Strengths and Limitations: This study is the first prospective trial of penile rehabilitation with tadalafil 5 mg once a day prior to nsRARP. This is a pilot study with the limitations of a small sample; further and large-scale studies with multiple cohorts, such as an untreated control group and an early immediate rehabilitation group for EF recovery, are needed. Conclusion: This study suggests that preoperative penile rehabilitation using tadalafil may lead to better erectile function recovery than postoperative penile rehabilitation using tadalafil.Noh T, Shim JS, Kang SG, et al. Efficacy of Tadalafil in Penile Rehabilitation Started Before Nerve-Sparing Robot-Assisted Radical Prostatectomy: A Double-Blind Pilot Study. Sex Med 2022;10:100508.

Results after radical prostatectomy (RP) are generally judged by complete removal of the cancer, return of urinary control, and the ability to have intercourse. Given the complexity of the anatomy of the prostate and its relationship to the surrounding nerves, muscles, and fascia, RP is considered a challenging and technically demanding surgery. Here we propose multiple intraoperative strategies to optimize oncological and functional outcomes. [ABSTRACT FROM AUTHOR]

Radical prostatectomy (RP) is a common procedure for localized and locally advanced prostate cancer (PCa). Despite advances in the technique with the introduction of robotic surgery, erectile dysfunction (ED) remains a major drawback. Therefore, a personalized evaluation that considers the patient's expectations and cultural background, baseline erectile function (EF), health status, and tumoral extension is important to optimize outcomes. Since EF has a tremendous impact on the quality of life of the patient and the intimate partner, it is timely to review multidisciplinary approaches to be implemented in the preoperative setting. Here we propose various strategies divided into two main categories, namely, comprehensive preoperative planning and prehabilitation (Figure 1.). [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to highlight the biopsychosocial recommendations provided to prostate cancer survivors and their partners during sexual rehabilitation. Methods: Retrospective analysis of a prospectively maintained patient database was conducted for visits between 2013 and 2019. The sexual health rehabilitation action plan (SHRAP) is a standardized 29-item list of biopsychosocial recommendations. The frequency of biopsychosocial recommendations provided to patients via their SHRAPs was assessed. Results: Among 913 patients, across 2671 appointments, nearly 74% of patients underwent radical prostatectomy. Other treatments included combination therapy (surgery, radiation, and/or androgen deprivation therapy (ADT)) (13%), radiation (external beam radiation or brachytherapy) (5%), and active surveillance (2%). Each patient had a median of 2 (SD 2.06) appointments and received a mean of 10.0 (SD 3.9) recommendations at each visit. Educational recommendations (penile rehabilitation, orgasmic guidelines, and climacturia management) were provided in 84% of visits followed by psychosexual recommendations (pleasure-focused, dedicated time, simmering, sexual aids, and sensate focus) in 71% of all appointments. The top recommendations (total n, frequency of recommendation) were penile rehabilitation (2253, 84%), pleasure-focus (1887, 71%), phosphodiesterase inhibitors (1655, 62%), clinical counselor (1603, 60%), vacuum erectile device (1418, 53%) and intracavernosal injections (1383, 52%). Conclusions: Biopsychosocial programs are evolving to be a key part of prostate cancer survivorship. This study's insight suggests that prostate cancer survivors require education around their sexual consequences and psychosexual counseling alongside proven biomedical strategies for erectile dysfunction. Implications for cancer survivors: Cancer survivorship programs should integrate educational and psychosocial strategies alongside biological strategies for prostate cancer survivors and their partners. [ABSTRACT FROM AUTHOR]

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.

Abstract Background A variety of penile rehabilitation (PR) therapies are available to improve post-prostatectomy erectile dysfunction (ED) with mixed results. It is uncertain how adherent men are to PR therapies. The aim of this study is to determine adherence to and identify barriers to PR treatment. Methods A longitudinal cross-sectional approach was used in men who underwent radical prostatectomy over 2 years. Men were instructed to take a PDE5 inhibitor (PDE5i) three times per week, and if required, utilize a vacuum constriction device (VCD) daily. Outcomes were measured by multiple validated questionnaires. In addition, penile stretched length, side effects, compliance to PR regimen & barriers to participation were documented. Results Seventy-seven patients were enrolled, however only 49 completed evaluation at 3 or more timepoints and were included in analysis. This cohort was an average age of 58.1 years (±7.7), had robotic laparoscopic radical prostatectomy (91.7%), and had bilateral nerve sparing procedures (95.8%). Majority (62.5%) reported normal SHIM pre-operatively, however 79% used PDE5i. Erectile function as measured by IIEF and Erection Hardness Rating were negatively affected post-operatively, with gradual improvement in parameters throughout the 24 month follow up. Of the participants who had normal pre-op SHIM, only 23.1 and 28.6% regained baseline function at 1 and 2 years, respectively. Orgasm was significantly diminished immediately post-operatively, however, at the end of the study period only 37% of men reported diminished climax and no men reported absent orgasm. Adherence to penile rehabilitation therapies declined overtime. Men took oral PDE5i on average 2.3 times weekly at 12 and 24 months (p

This study aimed to evaluate whether adding a vacuum erection device (VED) to regular use of Tadalafil could achieve better penile rehabilitation following posterior urethroplasty for pelvic fracture-related urethral injury (PFUI). Altogether, 78 PFUI patients with erectile dysfunction (ED) after primary posterior urethroplasty were enrolled and divided into two treatment groups: VED combined with Tadalafil (Group 1, n = 36) and Tadalafil only (Group 2, n = 42). Changes in penile length, testosterone level, International Index of Erectile Function-5 (IIEF-5) questionnaire, Quality of Erection Questionnaire (QEQ), and nocturnal penile tumescence (NPT) testing were used to assess erectile function before and after 6 months of ED treatment. Results showed that the addition of VED to regular use of Tadalafil preserved more penile length statistically (0.4 ± 0.9 vs −0.8 ± 0.7 cm, P < 0.01). IIEF-5 score and QEQ score in Group 1 were higher than Group 2 (both P < 0.05). After treatment, 21/36 (58.3%) Group 1 patients and 19/42 (45.2%) Group 2 patients could complete vaginal penetration. Group 1 patients also had markedly improved testosterone levels (P = 0.01). Unexpectedly, there was no significant difference in NPT testing between two therapies. For PFUI patients with ED after posterior urethroplasty, the addition of VED to regular use of Tadalafil could significantly improve their conditions – improving erection and increasing penile length – thus increasing patient satisfaction and confidence in penile rehabilitation.

Objective: To investigate the impact of penile rehabilitation on the recovery of erectile function after robot‐assisted radical prostatectomy. Methods: Patients who underwent robot‐assisted radical prostatectomy in our department from 2010 to 2019 were included. For penile rehabilitation, a phosphodiesterase‐5 inhibitor (tadalafil 20 mg) was administered twice a week for 1–6 months postoperatively. The International Index of Erectile Function questionnaire (question 1 and erectile function domain) and the Expanded Prostate Cancer Index Composite questionnaire (sexual function) were used. Results: After propensity score matching, there were 79 patients in the penile rehabilitation group and 79 patients in the non‐penile rehabilitation group. There was no significant difference in baseline characteristics between the two groups. Significantly higher scores were seen in the penile rehabilitation group compared with the non‐penile rehabilitation group at postoperative 3, 6 and 9 months in the International Index of Erectile Function questionnaire‐question 1, at 3, 6, 9 and 12 months in erectile function domain, and at 3, 6, 12 and 24 months in Expanded Prostate Cancer Index Composite questionnaire sexual function (P < 0.05). There were significant improvements in the erectile recovery rate in the penile rehabilitation group compared with the non‐penile rehabilitation group in the nerve sparing (P = 0.006) and partial nerve sparing (P = 0.037) groups. Conclusions: The present findings suggest that robot‐assisted radical prostatectomy patients who undergo not only nerve sparing, but also those who undergo patial nerve sparing could benefit from penile rehabilitation using a phosphodiesterase‐5 inhibitor. [ABSTRACT FROM AUTHOR]

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Background: Vacuum erectile device (VED) therapy has been widely used in penile rehabilitation after radical prostatectomy; however, there is no consensus on the best regimen. Objectives: To explore an optimal VED therapy regimen in bilateral cavernous nerve crush (BCNC) rat model. Materials and Methods: Adult male rats were used to measure the effects of different durations (1–30 min) of VED treatment on penile length, penile blood gas analysis, and adverse effects. Forty‐eight adult male rats were randomly divided into Sham, BCNC, and VED treatment groups (2–3–2–3 min, 4–3–3 min, 5–5 min, and 10 min). Penile length, erectile function, and side effects were detected after VED treatment. Histopathological staining and Western blotting were performed to explore the cellular and molecular changes. Results: Prolongation of the duration of VED treatment significantly decreased the penile oxygen saturation, partial oxygen pressure, and arterial blood ratio (P < 0.05). Compared with the BCNC group, all VED treatment regimens partially reversed BCNC‐induced penile shortening and erectile dysfunction (P < 0.0001), with the 4–3–3‐min and 5–5‐min treatment groups exhibiting more significant improvement than the 10‐min and 2–3–2–3‐min treatment groups (P < 0.0001). The mechanism may be related to the up‐regulation of the smooth muscle cell/collagen ratio, endothelial nitric oxide synthase, and α‐smooth muscle actin (all P < 0.0001); and the down‐regulation of hypoxia‐inducible factor‐1α, transforming growth factor‐β1, and apoptosis (all P < 0.0001). The incidence of adverse effects in the 2–3–2–3‐min treatment group was the highest. Discussion: The commonly used VED therapy regimens maintained erectile function and penile length of BCNC rat by relieving hypoxia and fibrosis, and no further benefits were observed with increased treatment frequency or prolonged treatment duration. Conclusion: Two consecutive 5‐min treatments with a short interval is the optimal VED therapy regimen for penile rehabilitation in BCNC rat model. [ABSTRACT FROM AUTHOR]

After radical prostatectomy (RP) or radiotherapy (RT) for prostate cancer, erectile dysfunction (ED) is the main complication next to urinary incontinence, affecting quality of life. The pathophysiology of ED after these treatments is believed to include neuropraxia causing reduced oxygenation and structural changes of the tissue in the corpora cavernosa. Next to the option of sparing the nerves during RP, research has been focusing on methods for penile rehabilitation after RP and RT, since it occurs often, even after nerve-sparing techniques were used. In animal studies, the use of phosphodiesterase type 5 inhibitors (PDE5i) after cavernous nerve damage is supported, but results in human studies are contradictory. Non-medical treatment options such as vacuum device therapy, hyperbaric oxygen therapy, yoga, aerobic, or pelvic floor training may be helpful, but evidence is scarce. Clear guidelines for penile rehabilitation are not yet available. However, care and support for ED after RP and RT is highly demanded by a large group of patients, so measures have to be taken even though the evidence is not strong yet. In this systematic review, an overview of the literature for penile rehabilitation and treatment options for ED after RP and RT is provided, using only randomized controlled trials (RCT).

Purpose: This aim was to study the efficacy of a vacuum erectile device (VED) in rehabilitating the erectile function of patients undergoing nerve-sparing robotic-assisted radical prostatectomy. Materials and Methods: This prospective randomized study enrolled 35 prostate cancer patients from Thailand who had intact baseline erectile function and underwent nerve-sparing robotic-assisted radical prostatectomy. These patients were randomly assigned into either a study group which applied the VED for 10 min daily for 6 months or a control group which received no additional interventions. A 5-item version of the International Index of Erectile Function (IIEF-5) score, stretched penile length, and midshaft circumference were measured at 1, 3, and 7 months after surgery, respectively. Results: The mean patient age was 65.6 years, and the mean baseline IIEF-5 score was 22.91, which were comparable between the two groups. Three patients in the study group did not follow the VED protocol due to postoperative urinary incontinence. A per-protocol analysis revealed that the mean IIEF-5 score at 7 months was significantly higher in the study group compared to the control group (11.29 ± 7.47 vs. 6.61 ± 5.33, P = 0.047). The mean midshaft circumference was also higher in the study group (9.24 ± 1.43 cm vs. 7.91 ± 0.37 cm, P = 0.002). No statistically significant difference in the mean stretched penile length between the two groups was found. Conclusion: Early VED usage for penile rehabilitation following radical prostatectomy significantly improves IIEF-5 score and better preserves penile circumference but not penile length. A larger-scale multi-institutional study is required to validate these findings. [ABSTRACT FROM AUTHOR]

Patients, after radical prostatectomy with the use of nerve-sparing techniques, without carrying out penile rehabilitation, are at risk of forming cavernous fibrosis with the emergence of subsequent persistent erectile dysfunction. In order to minimize damage to cavernous tissue and early restoration of erectile function during the period of neuropraxia, it is necessary to ensure a sufficient level of oxygenation. The role of applying vacuum in penile rehabilitation for the prevention of hypoxia of cavernous tissue is not fully understood, due to the lack of data on the gaseous composition of the blood at the time of reaching the vacuum of erection. The purpose of this work was to review the scientific studies devoted to the study of vacuum induced penile erection in animals or humans, which indicates high results due to increased oxygenation of cavernous tissue.

Erectile dysfunction (ED) after radical prostatectomy (RP) still represents a major issue. Considering the benefits recently described regarding the application of low-intensity extracorporeal shockwave therapy (LiESWT) in vasculogenic ED, questions arise about its role in the scenario of penile rehabilitation. To compare the early introduction of phosphodiesterase-5 inhibitor (PDE5i) with a combination therapy enrolling both early PDE5i use and LiESWT in patients submitted to RP. This study is a randomized clinical trial, open-label, with 2 parallel arms and an allocation ratio of 1:1. The study was registered in ReBEC (ensaiosclinicos.gov.br) Trial: RBR-85HGCG. Both arms started tadalafil at a dose of 5 mg/day right after the removal of the transurethral catheter, and the experimental group received 2,400 shocks/session-week distributed on 4 different penile regions. The full treatment consisted of 19,200 impulses across 8 weeks. The primary clincal end point was ≥4-point difference favoring the experimental group considering the mean International Index of Erectile Function short form (IIEF-5) at last follow-up. Any statistical difference in the IIEF-5 score between the arms was stated as the primary statistical end point. Between September 25, 2017, and December 3, 2018, 92 men were enrolled in the study. At last follow-up, we assessed 77 patients, 41 in the control group and 36 in the intervention group. A difference between groups was detected when accessing the final median IIEF-5 score (12.0 vs 10.0; P =.006). However, the primary clinical endpoint considering a difference ≥4-point between the arms has not been reached. When performing an exploratory analysis comparing the proportion of those individuals with an IIEF-5 score ≥17, no difference between groups was noted (17.1% vs 22.2%; P =.57). So far, the benefits arising from LiESWT for penile rehabilitation after RP have been uncertain. This is the first trial assessing the role of LiESWT on erectile function after RP. Our study protocol included only one session per week for the experimental group, raising a query if a more intensive application could achieve better results once a statistically significant difference was found between groups. We discontinue the PDE5i use at the last session, which may have interfered in the penile vascular rehabilitation, maybe compromising the results too. After therapy with 19,200 impulses therapy across 8 weeks, we found an improvement of the IIEF-5 score, but it was not enough to be considered clinically significant. More studies are warranted before any recommendation on this topic. Baccaglini W, Pazeto CL, Corrêa Barros EA, et al. The Role of the Low-Intensity Extracorporeal Shockwave Therapy on Penile Rehabilitation After Radical Prostatectomy: A Randomized Clinical Trial. J Sex Med 2020;17:688–694. [ABSTRACT FROM AUTHOR]

Vacuum erection device (VED), used to treat radical prostatectomy (RP)-associated erectile dysfunction, has attracted considerable attention. However, the optimal negative pressure remains to be determined. This investigation explored the optimal pressure for VED therapy in penile rehabilitation. Thirty-six 9-week-old male rats were randomly divided into six groups: control groups (sham group, bilateral cavernous nerve crush [BCNC] group) and VED therapy groups (-200 mmHg group, -300 mmHg group, -400 mmHg group, -500 mmHg group). BCNC group and VED therapy groups underwent BCNC surgery. Intracavernosal pressure (ICP)/mean arterial pressure (MAP) ratio was calculated to assess erectile function. Masson's trichrome (MT) staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, immunohistochemistry, and real-time polymerase chain reaction (RT-PCR) were performed to explore cellular and molecular changes of the penis. Compared to the BCNC group, ICP/MAP ratios in all VED treatment groups were improved significantly (all P < 0.05), but there were no statistically significant differences among VED therapy groups. With increased pressure, complications gradually emerged and increased in frequency. Expression of molecular indicators, such as endothelial nitric oxide synthase (eNOS) and alpha-smooth muscle actin (α-SMA), increased after VED therapy, and hypoxia-inducible factor 1α (HIF-1α) and transforming growth factor beta (TGF-β) decreased. In addition, VED therapy improved the outcomes of MT and TUNEL assay. This investigation demonstrated a pressure of -200 mmHg in a rat model is optimal for VED therapy for penile rehabilitation after RP. No further benefits were observed with increased pressure, despite an increase in complications. [ABSTRACT FROM AUTHOR]

Radical prostatectomy has significantly improved prostate cancer survival rates but continues to have a negative impact on the patient's erectile function (EF). In attempts to improve erectile dysfunction (ED), clinicians have incorporated different treatment modalities to restore EF. Penile rehabilitation consists of understanding the mechanisms that affect post-prostatectomy EF and utilizing pharmacologic agents, devices, and interventions to promote the male sexual function. This article aims to summarize the available scientific research involving penile rehabilitation. Even though the current literature lacks to prove its irrefutable effectiveness, penile rehabilitation has a positive impact at the molecular and cellular levels, and it is widely adopted in clinic practices. [ABSTRACT FROM AUTHOR]