Sural Nerve Interposition Grafting during Radical Prostatectomy

In 1997, autologous sural nerve grafting to reconstruct bilaterally resected cavernosal nerves was successfully performed in patients undergoing radical retropubic prostatectomy. After 12 months, one third of these patients had erections sufficient for intercourse. Since that time, patients who have had neurovascular bundle resection and sural nerve grafting have continued to show promising results. For example, within one large cohort of men who had unilateral, nerve-sparing radical prostatectomy, significantly more men who had sural nerve grafting regained potency, and did so in less time, than men who did not have grafting. More importantly, however, with better predictions of the presence of extracapsular disease, nerve-sparing surgery can be performed more selectively, reserving wide resection and sural nerve grafting for patients likely to have extracapsular extension. A multicenter, randomized clinical trial is needed to substantiate the positive outcomes observed with sural nerve grafting.     

Cavernous nerve stimulation and interposition grafting: a critical assessment and future perspectives

The sexual dysfunction that results from radical prostatectomy for carcinoma of the prostate is well established, with the degree of macroscopic preservation of the cavernous nerves tied to the degree of postoperative recovery of erectile function that is possible. In addition to the use of preoperative neuroprotective drugs and postoperative erectogenic agents, intraoperative nerve stimulation and grafting offer promise. Nerve stimulation may serve as a predictor of postoperative potency, and nerve grafting offers a potential way to correct the damage that occurs during wide resection. This article reviews the current literature on these intraoperative measures and discusses the need for additional studies of their potential benefits in prostatectomy candidates.     

Advances in the Management of Post-Radical Prostatectomy Erectile Dysfunction: Treatment Strategies When PDE-5 Inhibitors Don't Work

Phosphodiesterase type-5 (PDE-5) inhibitors have revolutionized the treatment of post-radical prostatectomy erectile dysfunction. For those patients who undergo a non-nerve-sparing radical prostatectomy or whose condition fails to respond to PDE-5 inhibitors, alternative treatment with intracavernous injection therapy, transurethral alprostadil, vacuum erection devices, and recently described combination therapy is available. The goals of therapy are to provide the patient with a means of obtaining an erection so that the patient and his partner may resume sexual relations as soon as possible following radical prostatectomy. There is evidence that early institution of treatment may promote improvement in the return of spontaneous erections in patients who have undergone nerve preservation. In patients who undergo non-nerve-sparing procedures, therapy may improve penile rigidity. Intracavernous injection therapy, transurethral alprostadil, and vacuum devices are highly effective in the management of post-prostatectomy erectile dysfunction. High dropout rates, which are not related to adverse effects, have been described with all 3 modalities. Pre- and postoperative counseling may improve patient and partner satisfaction.     

A review of surgical techniques for radical prostatectomy

Since the early 20th century, radical prostatectomy has been used in the treatment of prostate cancer. However, before the widespread acceptance of prostate-specific antigen screening, the majority of cancers were clinically advanced and not amenable to cure, so relatively few men were candidates for this procedure. Modern advances have contributed dramatically to the reduction of complications and morbidity associated with radical prostatectomy. As a result, the procedure has become the most common treatment selected by men with localized prostate cancer. This article reviews several issues regarding radical prostatectomy, including surgical techniques, cancer control, intraoperative localization of the cavernous nerves, patient selection, and laparoscopic versus robotic approaches.     

Changes of nitric oxide synthase-containing nerve fibers and parameters for oxidative stress after unilateral cavernous nerve resection or manuplation in rat penis

After pelvic surgeries such as radical prostatectomy, two major complications--urinary incontinence and erectile dysfunction (ED) may occur. Etiologies for ED are multiple pathologic mediators/systems. Oxidative stress, which is known to be induced after surgical trauma, could be a cause of ED. The purposes of in this study are to investigate the effect of unilateral manipulation/ dissection and resection of the cavernous nerve (neurotomy) to NOS (nitric oxide synthase)-containing nerve fibers and pressure after electro stimulation in rat corpus cavernosum, and to determine whether these procedures would produce oxidative stress within rat cavernous tissue 3 weeks and 6 months after the operation. Male rats were divided into 5 groups. Rats in groups 1 and 2 underwent unilateral cavernous nerve manipulation and sacrificed 3 weeks and 6 months after the operation, respectively. Rats in groups 3 and 4 underwent unilateral neurotomy of a 5-mm. segment of the cavernous nerve, and they were sacrificed 3 weeks and 6 months after nerve ablation, respectively. Group 5 rats were control animals for biochemical analysis. Intracavernous pressure following electro stimulation reduced is significantly 3 weeks after unilateral resection, as compared to that of the manipulated nerve (P < 0.05), and it recovered 6 months after neurotomy. The recovery was also confirmed by NADPH (nicotinamide adenine dinucleotide phosphate) diaphorase staining in neurotomy groups. Lipid peroxidation, which is an indicater of oxidative stress, was determined by measuring thiobarbituric acid reacting substance (TBARS) levels and superoxide dismutase (SOD) activity. These markers indicated that unilateral cavernous nerve manipulation or resection produced oxidative stress within rat corpus cavernosum. Oxidative stress was more prominent 3 weeks after unilateral neurotomy (P < 0.05). Also, compared to the control animal group, oxidative stress was observed three weeks after manipulation of unilateral cavernous nerve (P < 0.05). Resection of the cavernous nerve caused more prominent oxidative stress than in the manipulation group. This study suggested, that unilateral cavernous neurotomy caused a decrease of intra cavernous pressure and NOS fibers in rat corpus cavernosum, and they recovered 6 months after neurotomy. Our data also provided evidence that neurotomy and manipulation of the cavernous nerve caused oxidative stress in rat corpus cavernosum and that oxidative stress was more prominent in the nerve resection group.     

Troubles sexuels après curiethérapie par implants permanents d’I-125 dans le cancer localisé de prostate

Brachytherapy by permanent implants is an alternative to radical prostatectomy or external beam radiotherapy for good prognosis localized prostate cancer. The advantages of this treatment are effective and precise irradiation, limited to the prostate gland with moderate and transient morbidity. Erectile dysfunction, frequent erection after surgery and external beam radiotherapy, is observed in 6% to 61% of cases in the literature after brachytherapy. This wide range is related to differences in terms of follow-up, definition of sexual disorders, and the measuring instruments used. These erectile disorders occur between 9 and 17 months after treatment and appear to be related to vascular radiation lesions of the erectile bodies close to the prostatic apex (urethral bulb and base of the corpora cavernosa). However, the majority of erectile disorders respond favourably to oral treatments such as yohimbine or sildenafil. Among the various curative treatment options for localized prostate cancer, permanent implant brachytherapy is the treatment ensuring the best preservation of erectile function.     

Erectile Function Restoration After Repair of Resected Cavernous Nerves by Adipose-Derived Stem Cells Combined with Autologous Vein Graft in Rats

Cavernous nerve (CN) injury is the main cause of erectile dysfunction (ED) following radical prostatectomy. The recovery of erectile function following this procedure remains challenging. Here, we investigated the ability of adipose-derived stem cells (ADSCs) combined with autologous vein graft to improve erectile function in a rat model of bilateral long CN resection. Sprague–Dawley rats (n = 36) were randomized into four groups. Group A underwent sham operation. In Groups B, C, and D, an 8-mm segment of CN was excised bilaterally. In Group B and C, a 10-mm segment of autologous saphenous vein was interposed bilaterally at the site of injury, and the two nerve stumps were inserted into the vein lumen. 50 μL ADSCs were injected into each vein in Group B, and 50 μL of phosphate-buffered saline was injected in Group C. Group D underwent no repair. Erectile function assessed after 3 months by measuring intracavernosal pressure demonstrated significant recovery in erectile function in Group B with minimal recovery in Group C or D. Immunohistochemical staining showed that the nNOS-positive area was significantly larger in Group B than in Group D. ADSCs combined with autologous vein graft treatment had beneficial effects on the smooth muscle/collagen ratio in the corpus cavernosum. This procedure, therefore, provided a means of regenerating CN tissue and restoring autonomic erectile function after long bilateral CN resection (0.8 cm) in rats.     

Reconstruction of the Abdominal Vagus Nerve Using Sural Nerve Grafts in Canine Models

Background

Recently, vagus nerve preservation or reconstruction of vagus has received increasing attention. The present study aimed to investigate the feasibility of reconstructing the severed vagal trunk using an autologous sural nerve graft.

Methods

Ten adult Beagle dogs were randomly assigned to two groups of five, the nerve grafting group (TG) and the vagal resection group (VG). The gastric secretion and emptying functions in both groups were assessed using Hollander insulin and acetaminophen tests before surgery and three months after surgery. All dogs underwent laparotomy under general anesthesia. In TG group, latency and conduction velocity of the action potential in a vagal trunk were measured, and then nerves of 4 cm long were cut from the abdominal anterior and posterior vagal trunks. Two segments of autologous sural nerve were collected for performing end-to-end anastomoses with the cut ends of vagal trunk (8–0 nylon suture, 3 sutures for each anastomosis). Dogs in VG group only underwent partial resections of the anterior and posterior vagal trunks. Laparotomy was performed in dogs of TG group, and latency and conduction velocity of the action potential in their vagal trunks were measured. The grafted nerve segment was removed, and stained with anti-neurofilament protein and toluidine blue.

Results

Latency of the action potential in the vagal trunk was longer after surgery than before surgery in TG group, while the conduction velocity was lower after surgery. The gastric secretion and emptying functions were weaker after surgery in dogs of both groups, but in TG group they were significantly better than in VG group. Anti-neurofilament protein staining and toluidine blue staining showed there were nerve fibers crossing the anastomosis of the vagus and sural nerves in dogs of TG group.

Conclusion

Reconstruction of the vagus nerve using the sural nerve is technically feasible.     

Management of clinically localized prostate cancer

Critics of screening have stated that early detection of prostate cancer does not necessarily reflect a diminishing death rate from the disease. However, several recent reports have demonstrated that the death rate from prostate cancer is decreasing, representing the most compelling validation for aggressive screening. Prostate cancer can be halted only if there is no evidence of systemic or regional metastases and the disease is confined to the surgical field or the radiation template. Surgeons and radiation oncologists must make a concerted effort to exclude men with regional and systemic metastases who are unlikely to benefit from treatment. With the widespread acceptance of prostate-specific antigen screening, a greater proportion of men are being diagnosed with clinically localized prostate cancer. Both radical prostatectomy and radiation therapy are able to halt disease spread in this significant subset of men, but survival outcomes indicate that radical prostatectomy is a more reliable treatment than radiation therapy for clinically localized prostate cancer. Overall, the immediate treatment-related morbidity of radical prostatectomy and radiation therapy in the modern era is quite low. Radical prostatectomy and radiation therapy appear to have a similar impact on continence and erectile function. There is a need for neoadjuvant and adjuvant therapies that can be utilized in those cases where radical prostatectomy and radiation are less likely to completely eradicate or destroy the cancer.     

Erectile function outcomes in the current era of anatomic nerve-sparing radical prostatectomy

The contemporary use of anatomic nerve-sparing radical prostatectomy, which entails preserving the autonomic nerve supply to the penis required for penile erection, has led to improved erectile function outcomes compared with what has been seen historically. However, delay of postoperative recovery of erection for as long as 2 years is common, such that dysfunctional erection status lingers as a major postoperative problem. Several possible strategies to improve overall recovery rates and to hasten postoperative recovery of erectile function are currently being advanced. These include pharmacologic rehabilitation therapy and neuromodulatory therapy. Rigorous basic scientific investigation and clinical assessment of these new strategic approaches are critically important to establish their actual therapeutic benefits.     

Neuroregenerative strategies after radical prostatectomy

Patients with erectile dysfunction (ED) following radical prostatectomy (RP) continue to present to practicing urologists. Although nerve-sparing RP has decreased the rates of ED significantly, new therapies for cavernosal nerve protection and recovery are now being developed. This report discusses the many agents available in neuroregeneration and neuroprotection to aid in the recovery of erectile function. Multiple agents and strategies have been used for neuroprotection and neuroregeneration of the cavernosal nerve following RP and in nerve injury models. Many of these agents display promise for the treatment of impotence. Early treatment for patients recovering from RP is becoming the standard of care. Natural recovery of erections may take as long as 18 to 24 months post RP; however, treatment plans may reduce the time to erectile recovery.     

Regulation of cavernous nerve injury-induced apoptosis by sonic hedgehog

Thirty to eighty-seven percent of patients treated by radical prostatectomy experience erectile dysfunction (ED). The reduced efficacy of treatments in this population makes novel therapeutic approaches to treat ED essential. We propose that abundant apoptosis observed in penile smooth muscle when the cavernous nerve (CN) is cut (mimicking the neural injury which can result from prostatectomy) is a major contributing factor to ED development. We hypothesize that decreased Sonic hedgehog (SHH) signaling is a cause of ED in neurological models of impotence by increasing apoptosis in penile smooth muscle. We examined this hypothesis in a bilateral CN injury model of ED. We found that the active form of SHH protein was significantly decreased 1.2-fold following CN injury, that SHH inhibition causes a 12-fold increase in smooth muscle apoptosis in the penis, and that SHH treatment at the time of CN injury was able to decrease CN injury-induced apoptosis (1-3-fold) in a dose-dependent manner. These results show that SHH stabilizes the alterations of the corpora cavernosal smooth muscle following nerve injury.     

Safety of autologous bone marrow-derived mesenchymal stem cells in erectile dysfunction: an open-label phase 1 clinical trial

Background aimsThe efficacy of phosphodiesterase type 5 inhibitors (PDE5Is), which are commonly used to treat erectile dysfunction (ED), is not satisfactory in patients with denervation of the cavernous nerve due to pelvic surgeries and diabetes mellitus (DM). Pre-clinical studies using bone marrow-derived mesenchymal stem cells (BMSCs) to treat ED have shown promising results. The authors conducted a phase 1 clinical trial with autologous BMSCs in patients with ED due to radical prostatectomy or DM.MethodsTen patients (five with post-prostatectomy ED and five with DM-associated ED) who could not perform sexual activity despite taking the maximum dose of a PDE5I were enrolled. The brief clinical trial protocol was registered with the US National Institutes of Health on ClinicalTrials.gov (NCT02344849). The primary outcome was the safety of stem cell therapy, and the secondary outcome was the improvement of erectile function.ResultsOf the 13 patients screened, 10 were registered in the clinical trial and received autologous BMSCs and nine completed the clinical trial. One patient with post-prostatectomy ED experienced two treatment-emergent adverse events (TEAEs) (pyrexia and back pain), and two patients with DM-associated ED experienced a total of five TEAEs (one case each of viral upper respiratory tract infection, prostatitis and pruritus and two cases of hyperglycemia). Of these patients, one with DM-associated ED experienced two serious TEAEs (two instances of hyperglycemia). All TEAEs were considered not to be related to autologous BMSC therapy. In addition, no clinical significance was identified related to other safety measures, such as laboratory tests and vital signs. The mean International Index of Erectile Function score increased significantly at 1 month versus baseline (24.9 versus 18.1, P = 0.0222).ConclusionsThis phase 1 clinical trial confirmed the safety and potential efficacy of autologous BMSC therapy in patients with ED. The authors’ results need to be confirmed by a phase 2 clinical trial.     

The harvest and clinical application of the superficial peroneal sensory nerve for grafting motor and sensory nerve defects.

Potential donor nerves for autografting are finite and usually limited to cutaneous nerves of the extremities. The superficial peroneal nerve is the major lateral branch of the common peroneal nerve that innervates the peroneus longus and brevis muscles and provides sensation to the lateral aspect of the lower leg and the dorsal foot. It has generally been overlooked as a potential donor of nerve autografts. Cadaver dissections were performed on 10 fresh lower extremity specimens to investigate the anatomic characteristics of the superficial peroneal nerve and to refine a harvesting technique for the nerve. Thirty-one patients underwent nerve grafting of 39 upper and lower extremity nerves using the superficial peroneal donor. There were nine median nerves, four ulnar nerves, two radial nerves, two brachial plexus lesions, 16 digital nerves, and six lower extremity nerves grafted. The superficial peroneal nerve provided a consistently long donor, comparable in length to the sural nerve. The anatomic pattern is consistent, the patient positioning is simple, the surgical harvesting technique is straightforward, and the donor defect is acceptable. The superficial peroneal nerve provides a safe and valuable donor nerve, particularly in cases where multiple or very long nerve grafts are required.     

A prospective clinical evaluation of autogenous vein grafts used as a nerve conduit for distal sensory nerve defects of 3 cm or less

The purpose of this study was to determine the efficacy of autogenous vein grafts as nerve grafts (AVNC) for bridging of small peripheral sensory nerve gaps as compared with direct repair and with conventional nerve grafting techniques (ANG). Patients with painful neuroma or segmental nerve injury of 3 cm were chosen as the test group. Those amenable to direct repair were classified as controls. Between 1982 to 1988, a total of 22 patients were enrolled in this study. A total of 34 nerves were repaired, 15 with a venous nerve conduit, 4 with a sural nerve graft, and 15 with direct repair. Significant symptom relief and satisfactory sensory function return were uniformly observed. The two-point discrimination measurements indicated superiority of direct repair and probably of conventional nerve grafting. However, the universally favorable patient acceptance and the return of measurable two-point discrimination indicates the effectiveness of autogenous vein grafts as nerve conduits when selectively applied to bridge a small nerve gap (less than or equal to 3 cm) on nonessential peripheral sensory nerves.     

The Use of Vacuum Erection Devices in Erectile Dysfunction After Radical Prostatectomy

The risk of postoperative erectile dysfunction (ED) following radical prostatectomy (RP) is reported to be between 14% and 89%. With an increase in the detection of prostate cancer in younger men, there is a greater emphasis on the appropriate management of ED following RP. A number of options are available to manage ED after RP, including phosphodiesterase-5 inhibitors, intracorporeal injections, intraurethral alprostadil, and vacuum erection devices (VEDs). Penile rehabilitation programs are increasingly used to facilitate the return of natural postoperative erections; the VED is an ideal therapy given that it increases blood flow and oxygenation to the corpora to reverse the changes that result in ED after RP.Key words: Erectile dysfunction, Radical prostatectomy, Vacuum erection device, Penile rehabilitationProstate cancer is the most common cancer in men over the age of 50 years.¹ When patients undergo a radical prostatectomy (RP), there is a risk of postoperative erectile dysfunction (ED). The incidence of ED following RP has been reported to be between 14% and 89%.² With an increase in the detection of prostate cancer in younger men, there is a greater emphasis on the appropriate management of ED after RP. With an early diagnosis of prostate cancer, there is an increase in the rate of RP in younger men and the importance of ED as a quality-of-life issue has subsequently increased.² There are a number of options available to manage ED after RP, including phosphodiesterase-5 (PDE-5) inhibitors, intracorporeal injections, intraurethral alprostadil, and vacuum erection devices (VEDs). Despite highly reported satisfaction and efficacy with VEDs, there is a move by some medical practitioners away from VEDs due to cost. But what evidence is there for VED success after prostatectomy and what role do VEDs have in penile rehabilitation after ED? We present current evidence and provide our recommendations based on the latest literature.     

Haemangiomas of the orbit

The authors describe their experience with systemic therapy of cavernous haemangiomas making use of interferon alpha. They have successfully used the method in treating two female patients with cavernous haemangiomas in the orbit. In the first patient, the IFN therapy was followed by surgical removal of the tumour. In the second patient, surgical operation was not suitable. After the IFN therapy, the patient's state improved both subjectively and objectively. Decreased level of bFGF in urine prove to be the criterion for successful treatment by IFN. The authors also stress the risk of complications in sucklings. When choosing the method of treatment, they emphasize the necessity of interdisciplinary cooperation.     

Effects of Intracavernous Injection of Adipose-Derived Stem Cells on Cavernous Nerve Regeneration in a Rat Model

The aim of this study was to investigate effects of intracavernous injection of adipose-derived stem cells (ADSCs) on cavernous nerve (CN) regeneration and functional status in a nerve-crush rat model. Thirty Sprague–Dawley male rats were randomly divided into three equal groups: one group underwent sham operation, while two groups underwent bilateral CN crush. Crush-injury group was treated at the time of injury with intracavernous injection of ADSCs, or injured control group with no further intervention. Erectile function was assessed by CN electrostimulation after 3 months. Penile tissue and crushed nerves were collected for histology. Three months after surgery, in the group that underwent bilateral nerve crushing with no further intervention, the functional evaluation showed a lower mean maximal intracavernous pressure (ICP) and maximal ICP per mean arterial pressure (MAP) with CN stimulation than those in the sham group. In the group with an immediate intracavernous injection of ADSCs, the mean maximal ICP and maximal ICP/MAP were significantly higher than those in the injured control group. Histologically, the group with the intracavernous injection of ADSCs had more myelinated axons of CNs and more NADPH-diaphorase-positive nerve fibers than the injured control group but fewer than the sham group. Intracavernous injection of ADSCs treatment had beneficial effects on the smooth muscle/collagen ratio in the corpus cavernosum. These results show that the intracavernous injection of ADSCs to the site of CN-crush injury facilitates nerve regeneration and recovery of erectile function. Our research indicates that penile injection of ADSCs can improve recovery of erectile function in a rat model of neurogenic ED.     

Sensitivity of breasts reconstructed with the autologous latissimus dorsi flap

The purpose of this study was to measure, both objectively and subjectively, the sensitivity of breasts reconstructed with the autologous latissimus dorsi flap and to compare these results with those of other reconstruction techniques, especially the transverse rectus abdominis myocutaneous flap. The study population included 50 patients with autologous latissimus dorsi flap breast reconstruction; these patients had an average age of 51 years and an average follow-up of 27 months. Patients answered a seven-item questionnaire that attempted to define the sensitivity of the reconstructed and opposite breasts. This sensitivity was then measured objectively using standard techniques for heat, cold, and tactile sensations. After statistical analysis, these results were compared with those published for other reconstruction techniques. Overall results were comparable or superior to those published for other techniques for autologous breast reconstruction. A total of 56 percent of patients had fine or very fine sensitivity, but 70 percent deemed this sensitivity to be less than that of the opposite breast. A total of 94 percent of patients perceived the reconstructed breast as integral to their body image. The superior medial part of the breast had the greatest sensitivity, both objectively and subjectively. Autologous latissimus dorsi breast reconstruction, a good technique with excellent aesthetic results, affords satisfactory sensitivity. This is yet another advantage of the technique.