Long-term efficacy and compliance of intracorporeal (IC) injection for erectile dysfunction following radical prostatectomy: SHIM (IIEF-5) analysis

Baseline and follow-up data from 102 patients using intracorporeal (IC) injection for erectile dysfunction (ED) following RP were retrospectively collected. We compared baseline International Index for Erectile Function (IIEF) questionnaires with the abridged IIEF-5 questionnaires, referred to as the Sexual Health Inventory of Men (SHIM) to determine drug efficacy. The mean presurgery SHIM score was 21.75+/-5.23, which decreased to 4.23+/-3.48 after surgery and increased to 19.46+/-8.78 post-treatment. Overall, 68% (69/102) of patients achieved and maintained erections sufficient for sexual intercourse and 48% (49/102) of patients continued long-term therapy with a mean use of 3.7+/-1.9 y. In all, 52% (53/102) patients discontinued IC therapy. However when excluding patients who switched to oral therapy, had loss of partner or return of normal erections; the compliance to IC injections was 70.6% (71/102). There was no difference in the SHIM analysis between the nerve sparing (NS) and the non-NS or between the types of medications used. IC injections can provide excellent long-term efficacy and compliance in up to 70% of the patients. This study suggests that IC injections are an excellent salvage option in NS patients who fail oral therapy and a first option in patients with non-NS procedures.     

Management of erectile dysfunction following radical prostatectomy

Radical prostatectomy is the standard treatment for organ/ specimen-confined prostate cancer, yet erectile dysfunction in selected series is still reported as high as 90% after this procedure. Thus, most men need adjuvant treatments to be sexually active following radical prostatectomy. These include vacuum constriction devices, intracorporeal injections of vasoactive drugs, and transurethral dilators, all of which have reported response rates of 50% to 70%. Unfortunately, long-term compliance is suboptimal, with a discontinuation rate of nearly 50% at one year. These non-oral options should be offered on an individual basis to patients who have failed oral therapy since efficacy and compliance vary. Also, these options should be considered in the early postoperative period to enhance sexual activity and penile oxygenation, which may prevent corporeal fibrosis. Early penile rehabilitation with intracavernosal injections or vacuum constriction devices should be encouraged to increase chances for recovery of rigid erections. In patients with some preservation of nerve tissue, oral sildenafil may be effective in promoting an earlier return of erectile function. The potential impact of sildenafil and other new oral therapies should encourage urologists to continue to perform and perfect the nerve-sparing approach.     

Prevention and management of erectile dysfunction following radical prostatectomy

Most studies indicate general satisfaction rates of greater than 80% after radical retropubic prostatectomy. Nonetheless, erectile dysfunction remains the most common problem postoperatively, with rates ranging from 100% to 10% depending on the experience of the surgeon, the frequency with which he or she performs the surgery, the nerve-sparing nature of the procedure, the stage of the disease, and the age and preoperative potency of the patient. The natural recovery of erection function takes as long as 24 months and can be expedited by early treatment with intracorporal injection therapy. The treatment of erectile dysfunction after radical retropubic prostatectomy is highly successful despite the finding that fewer than 50% of patients seek treatment. Sildenafil does not seem to be effective early in the recovery phase but increases in efficacy as the nerves recover from intraoperative injury. Other modalities in the early recovery phase in the order of increasing effectiveness are intraurethral prostaglandin, the vacuum erection device, and intracorporal injection therapy. After 2 years from surgery, the recovery of natural function and improved sildenafil responsiveness are unlikely, and the implantation of a prosthesis is reasonable if other modalities are ineffective or unacceptable for the patient. Animal studies and human trials are underway to examine ways to expedite and maximize the return of erectile function.     

Current and future strategies for preventing and managing erectile dysfunction following radical prostatectomy

INTRODUCTION AND OBJECTIVES: As radical prostatectomy remains a commonly used procedure in the treatment of clinically localized prostate cancer, we critically analyzed current and future strategies for preventing and managing postoperative erectile dysfunction. METHODS: Systematic literature review using Medline and CancerLit from January 1997 to June 2003. Abstracts published in the journals European Urology, The Journal of Urology and the International Journal of Impotence Research as official proceedings of internationally known scientific societies held in the same time period were also assessed. RESULTS: Patient selection and surgical technique are the major determinants of postoperative erectile function. Apoptosis of corporeal smooth muscle cells plays a role in the development of cavernous veno-occlusive dysfunction following radical prostatectomy. Pharmacological prophylaxis and treatment of postoperative erectile dysfunction is effective and safe. The concepts of cavernous nerve reconstruction and neuroprotection have been associated to promising results. CONCLUSIONS: In the hands of experienced surgeons, properly selected patients undergoing a nerve sparing radical prostatectomy should achieve unassisted or medically assisted erections postoperatively.     

他达拉非用于前列腺术后阴茎康复的研究进展

前列腺癌根治性切除术(RP)是治疗绝大多数临床局限性前列腺癌的标准术式,保留神经的NSRRP术式的广泛采用使得RP的疗效得到了显著的提升,但是对RP术后勃起功能的保护仍是泌尿外科的难题。RP术后及早开始阴茎康复可显著改善RP术后勃起功能障碍(ED)对患者的术后生活质量。作为唯一的长效选择性磷酸二酯酶-5抑制剂(PDE5Is),他达拉非在RP术后阴茎康复中的显著疗效在临床试验和基础研究中均得到了证实。本文旨在回顾目前RP术后ED的相关进展,及他达拉非在RP术后阴茎康复中的有效性和安全性证据。     

A prospective evaluation of efficacy and compliance with a multistep treatment approach for erectile dysfunction in patients after non-nerve sparing radical prostatectomy

OBJECTIVE: To assess the response rate to different erectile aids in a consecutive series of patients treated with non-nerve sparing radical prostatectomy (NNSRP). PATIENTS AND METHODS: Ninety-four potent men were counselled about the different treatment options to restore an assisted erection before they had NNSRP. They were invited to participate in a multiphase protocol involving the sequential use of different erectile aids which aimed at restoring erectile function after surgery. The first proposed treatment was oral apomorphine sublingual. Patients with a positive response to the 1-item overall efficacy question and a minimum score of 3 in both question 3 and 4 of the International Index of Erectile Function were considered responders to oral pharmacotherapy. Treatment with sildenafil was then suggested to those not responding. If patients did not respond to oral pharmacotherapy a trial with a vacuum erectile device was offered; those not responding to this were then offered intracavernosal injection therapy with prostaglandin-E alone as the first option, followed by a mixture of vasoactive agents if needed. In those in whom injections also failed, a penile implant was recommended. At the 1-year follow-up visit all patients were offered a second trial with oral therapy regardless of the treatment currently in use. RESULTS: Seventy-six patients entered the protocol; there was no response to apomorphine. Five of 59 (8%) patients responded to sildenafil when they first used it at a mean of 7 months after NNSRP, while there were three additional responders in 22 patients who tried it for a second time a year later. Of patients achieving at least a complete tumescence sufficient for vaginal penetration, 52% and 60% were considered responders to the vacuum device and intracavernosal injections, respectively. Overall, 44% of patients enrolled in the protocol chose to use an erectile aid for at-home use. At the 1-year follow-up, only 20% of patients were still using an erectile aid, including two who had had a penile implant. CONCLUSIONS: Up to 10% of patients may achieve a clinically significant erection with sildenafil after NNSRP, but 80% will not be using any erectile aid at 1 year after surgery. In the present study protocol the proposed erectile aids were largely inadequate for treating the permanent erectile dysfunction that follows NNSRP.     

前列腺癌根治术后勃起功能障碍的相关问题

前列腺癌根治术后的勃起功能障碍一直是困扰泌尿外科医师的难题,并严重影响患者的生活质量.术中海绵体神经的损伤是造成术后勃起功能障碍的主要原因.随着保留神经血管束或重建海绵体神经的前列腺癌根治术的开展及腹腔镜技术、机器人辅助腹腔镜技术与治疗药物的应用,前列腺癌根治术后勃起功能障碍的发生率已逐渐下降.本文拟就前列腺癌根治术后勃起功能障碍的相关问题进行讨论,以促进前列腺癌根治术后勃起功能障碍防治措施的推广应用.     

Treatment of erectile dysfunction after radical prostatectomy with sildenafil citrate (Viagra)

Objectives. To determine whether the response to the new oral medication, sildenafil citrate (Viagra), was influenced by the presence or absence of the neurovascular bundles, as recent reports on its success did not specify the efficacy of the drug in patients with erectile dysfunction after radical prostatectomy.Methods. Baseline and follow-up data from 28 healthy patients presenting with erectile dysfunction after radical prostatectomy were obtained. Patients receiving any neoadjuvant/adjuvant hormones or adjuvant radiation therapy were excluded. Patients reported what their erectile status was before surgery, before sildenafil therapy, and after using a minimum of four doses of sildenafil. Both the patients and their spouses were interviewed using the Cleveland Clinic post-prostatectomy questionnaire, which includes questions about response to therapy, duration of intercourse, spousal satisfaction, side effects, and related topics. The patients were compared on the basis of the type of surgical procedure they had undergone—nerve sparing or non-nerve sparing. A positive response to sildenafil was defined as erection sufficient for vaginal penetration.Results. Of the 15 patients who had bilateral nerve-sparing procedures, 12 (80%) had a positive response to sildenafil, with a mean duration of 6.92 minutes of vaginal intercourse. These 12 patients also reported a spousal satisfaction rate of 80%. All 12 of the responders had a positive response within the first three doses, and 10 of the 12 responded with the first or second dose. None of the 3 patients who had undergone a unilateral nerve-sparing procedure responded, nor did any of the 10 patients who had undergone a non-nerve-sparing procedure. The two most common side effects of the drug were transient headaches (39%) and abnormal color vision (11%). No patients discontinued the medication because of side effects.Conclusions. Successful treatment of erectile dysfunction in a patient after prostatectomy with sildenafil citrate may depend on the presence of bilateral neurovascular bundles. No patient who had undergone a non-nerve-sparing procedure responded. Whether patients who undergo unilateral nerve-sparing procedures will respond to sildenafil is still unclear because of the small number of patients in our study. These findings should encourage urologists to continue to perform and perfect the nerve-sparing approach. The ability to restore potency with an oral medication after radical prostatectomy will impact our discussion with the patient on the surgical morbidity of radical prostatectomy.     

Nerve injury-related erectile dysfunction following nerve-sparing radical prostatectomy: A novel experimental dissection model

Objectives:   To establish a new experimental rat model in order to define the mechanisms of erectile dysfunction (ED) and to evaluate the changes of neuronal nitric oxide synthase (nNOS) in the pelvic ganglia following nerve-sparing radical prostatectomy.
Methods:   Sprague-Dawley rats were randomized to sham operation, bilateral cavernous nerve dissection (BCND) and bilateral cavernous nerve resection (BCNR) groups. In the BCND group, the cavernous nerves were only dissected bilaterally from the major pelvic ganglion (MPG) to the apex of the prostate without crushing or cutting. At 1, 2, 4 and 8 weeks after surgery, we examined intracavernous pressure along with arterial pressure (ICP/AP), retrograde dye tracing using Fluorogold (FG) and expression of nNOS in the MPG.
Results:   Intracavernous pressure and arterial pressure in the BCND group was significantly decreased at 2 and 4 weeks after surgery compared with the sham group, and improved at 8 weeks. The number of FG-positive cells in the MPG also recovered at 8 weeks. ICP/AP and FG-positive cells in the BCNR group were greatly decreased until 8 weeks. The percentage of nNOS-positive cells per total cells was not different between the sham and BCND groups during the experimental period, whereas that in the BCNR group gradually decreased with time.
Conclusions:   We established a novel rat model, in which cavernous nerve dissection alone caused nerve injury-related ED. We believe that this cavernous nerve dissection model might help clarify the mechanism of nerve injury-related ED and the recovery from ED after nerve-sparing radical prostatectomy.     

Rehabilitation of erectile function following radical prostatectomy

The concept of muscle rehabilitation after nerve injury is not a novel idea and is practiced in many branches of medicine, including urology. Bladder rehabilitation after spinal cord injury is universally practiced. The erectile dysfunction （ED） experienced after radical prostatectomy （RP） is increasingly recognized as being primarily neurogenic followed by secondary penile smooth muscle （SM） changes. There is unfortunately no standard approach to penile rehabilitation after RP because controlled prospective human studies are not available. This article reviews the epidemiology, experimental pathophysiological models, rationale for penile rehabilitation, and currently published rehabilitation strategies.     

根治性前列腺切除术后勃起功能障碍不同治疗方案的Meta分析

目的系统评价不同治疗方案对根治性前列腺切除术后勃起功能障碍(ED)的疗效。方法检索The CochraneLibrary、PubMed、EMbase、中国知网、维普以及万方数据库,检索时间从建库至2018年4月,纳入根治性前列腺切除术后ED不同治疗方案的临床研究,文献数据采用RevMan 5.3软件进行统计学分析,并行发表偏倚风险评估。结果共11篇随机对照研究及5篇病例对照研究纳入本项研究,累计病例2 012例。Meta分析结果显示,5型磷酸二酯酶抑制剂(PDE5-Is)对患者满意改善程度显著优于对照组[OR=1.73,95%CI(1.34,2.23),P0.01]。各亚组分析结果显示:真空负压勃起装置(VED)对患者满意度改善无显著疗效[OR=1.51,95%CI(0.76,3.00),P=0.24];阴茎海绵体药物注射前列腺素E1(PGE1)对患者满意度改善效果显著[OR=8.50,95%CI(3.09,23.42),P0.01]。偏倚分析显示纳入的研究结果无明显发表偏移。结论对于根治性前列腺切除术后ED患者,采用PDE5-Is可显著改善ED症状;而对于疗效不佳的患者,选择联合治疗是适宜之选。     

前列腺癌根治术后勃起功能障碍动物模型的建立

目的 对大鼠海绵体神经(CN)进行解剖并对其造成钳夹损伤,以建立前列腺癌根治术(RP)后勃起功能障碍(ED)的动物模型.方法 将36只雄性SD大鼠随机分为模型组、假手术组、正常组,术后4周通过阿朴吗啡(APO)实验及海绵体内压(ICP)/平均动脉压(MAP)测定、阴茎神经型一氧化氮合酶(nNOS)免疫组织化学检测以评估建立模型的效果.结果 术后4周3组大鼠的阴茎勃起率和平均勃起次数分别为0%和0次、100%(11/11)和(2.24±0.86)次、100%(12/12)和(2.39±0.92)次.模型组大鼠无明显勃起反应,假手术组、正常组可见明确勃起反应.电刺激盆腔星状神经节(MPG)前3组大鼠ICP/MAP分别为(0.13±0.04)、(0.10±0.03)、(0.12±0.03),电刺激MPG后分别为(0.12±0.05)、(0.57±0.08)、(0.58±0.06),电刺激MPG前3组ICP/MAP差异均无统计学意义(P＞0.05),模型组与假手术组、正常组的电刺激MPG后ICP/MAP差异有统计学意义(P＜0.05).3组大鼠阴茎nNOS阳性神经纤维数分别为(23.04±2.59)、(73.94±7.51)、(80.26±6.95),模型组大鼠阴茎nNOS阳性神经纤维数明显少于假手术组、正常组(P＜0.05).结论 大鼠CN结构与人类非常相似,CN钳夹损伤是建立RP术后ED模型的可靠的方法.

Abstract：

Objective To identify rat cavernous nerve (CN) and develop a rat model of erectile dysfunction (ED) after radical prostatectomy (RP) caused by injury of cavernous nerve.Methods Thirty-six male SD rats were were randomly divided into 3 groups:model group,sham-operation group and nomal group.Four weeks after surgery,rat models were evaluated by apomorphine test,ICP/MAP measurement and nNOS-positive nerve fibres in penis.Results The rats in model group had no erectilty in apomorphine test and electical stimulating MPG.The rats in sham-operation group and nomal group had erectility at the same conditions,accompanied with increased ICP/MAP in electrical stimulation ( P＜0.05 ).The nNOS-positive nerve fibres in model group ( 23.04 ± 2.59 ) were less than those in sham-operation group (73.94 ±7.51 ) and normal group (80.26 ±6.95 ).Conclusion Cavernous nerve in rats is highly similar to that in human beings.The rat model of erectile dysfunction after radical prostatectomy caused by cavernous nerve crush injury is reliable.     

Counselling for erectile dysfunction during inpatient rehabilitation after radical prostatectomy

For men erectile function is essential for quality of life. Besides urine incontinence postsurgical erectile dysfunction (ED) following radical prostatectomy (RPE) represents a significant and prevalent problem. One of the first approaches to this condition should be a consultation performed by professionals in a rehabilitation clinic. A total of 149 patients post RPE participated in this prospective study. All patients were questioned about their understanding of postoperative surgical ED after RPE and if affected they were asked about their own psychological burden as well as their knowledge of possible therapy options. The qualities of presurgical patient information as well as the modules of information pertaining to ED during the rehabilitation were evaluated. Of the patients, 53% expressed that they experienced a considerable burden due to postsurgical ED during their follow-up rehabilitation (AR group) and 70% of the patients during oncological rehabilitation treatment (rehab group). Men who were sexually more active prior to surgery suffered more from postsurgical ED than their less active counterparts. A negative correlation between psychological burden and age was found in the AR group, which however was levelled in the rehab group. Particularly in older patients the burden of ED increases with more time elapsing after the operation. The medical information on ED therapy options provided during the inpatient rehabilitation was considered to be essential by 60% of the men in the AR group and 48% of the patients in the rehab group. Therapeutic possibilities for postsurgical ED following RPE cannot always be given to patients in the preoperative phase or during their stay in the hospital. Since however a large majority of men suffer from postoperative ED following RPE a specialized inpatient urological rehabilitation is suited for a comprehensive consultation.     

Vacuum erection devices to treat erectile dysfunction and early penile rehabilitation following radical prostatectomy

Vacuum erection devices (VED) are becoming first-line therapies for erectile dysfunction and preservation (rehabilitation) of erectile function following treatment for prostate cancer. Currently, phosphodiesterase-5 inhibitors have limited efficacy in elderly patients or patients with moderate to severe diabetes, hypertension, and coronary artery disease. Alternative therapies, such as VED, have emerged as a primary option for patients refractory to oral therapy. VED has also been successfully used in combination treatment with oral therapy and penile injections. More recently, there has been interest in the use of VED in early intervention protocols to encourage corporeal rehabilitation and prevention of post-radical prostatectomy venoocclusive dysfunction. This is evident by the preservation of penile length and girth seen with the early use of the VED following radical prostatectomy. There are ongoing studies to help preserve penile length and girth with early use of VED following prostate brachytherapy and external beam radiation for prostate cancer. Recently, there has also been interest in VED to help maintain penile length following surgical correction of Peyronie’s disease and to increase penile size before implantation of the penile prosthesis.     

Management of erectile dysfunction after radical prostatectomy in 2007

As radical prostatectomy (RP) remains a commonly used procedure in the treatment of clinically localized prostate cancer, we critically analyzed the evidence suggesting the role of pharmacological prophylaxis and treatment of erectile dysfunction (ED) after surgery. Systematic literature review using Medline and Cancerlit from January 1997 to December 2006. Abstracts published in the journals European Urology, The Journal of Urology, The International Journal of Impotence Research and The Journal of Sexual Medicine as official proceedings of internationally known scientific Societies held in the same time period were also assessed. Patient selection and surgical technique (i.e., preservation of neurovascular bundles) are the major determinants of post-operative erectile function. Pharmacological treatment of post-operative ED, using either oral or local approaches, is effective and safe. Moreover, recent studies have shown that pharmacological prophylaxis early after RP can significantly improve the rate of erectile function recovery after surgery. Use of on-demand treatments for treatment of ED in patients subjected to RP has been shown to be highly effective, especially in case of properly selected young patients treated with a bilateral nerve-sparing approach by experienced surgeons. In this context, pharmacological prophylaxis may potentially have a significant expanding role in future strategies aimed at preserving post-operative erectile function.