Preservation Of Cavernous Nerves Research Articles

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

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

AB159. Intravenous preload of mesenchymal stem cells rescues erectile function in a rat model of cavernous nerve injury

ObjectiveErectile dysfunction (ED) following radical prostatectomy (RP) can occur as a result of cavernous nerve (CN) injury. Even with the surgical progress of CN preservation techniques and/or introduction of robot-assisted procedures, ED can occur after RP and decrease the patient’s quality of life. Therefore, it is necessary to pursue methods to reduce the number of ED patients. We previously reported the therapeutic efficacy of intravenous infusion of mesenchymal stem cells (MSCs) for neurological disorders. Currently, clinical trials for cerebral infarction (Phase III) and spinal cord injury (Phase II) are ongoing at our Hospital. The current hypothesis is that the key therapeutic mechanisms of transplanted MSCs in various models of nervous diseases are not only differentiation to neuronal and/or glial cells, but also secretion of neurotrophic factors that can provide for neuroprotection, induction of axonal sprouting and neovascularization. In this study we evaluated the potential preventive effects and mechanisms of intravenously preloaded MSCs for ED in a CN injury model.MethodsThe use of animals in this study was approved by the Animal Care and Use Committee of our institution. Male Sprague Dawley rats were used for this study. To assess erectile function, the CN was stimulated electrically, and we measured the intracavernous pressure (ICP) and arterial pressure (AP). ICP/AP and area under the curve of ICP (ICP-AUC) were used as indexes of erectile function. We measured the initial ICP/AP of pre-injury (normal) male SD rats. Then the rats were randomized into two groups (MSC and control groups). They were intravenously infused with MSCs (1.0×106 cells in 1 mL total fluid volume) and the other was infused with medium alone (1 mL DMEM) for sham control, respectively. Then CN injury was induced immediately after infusion. We measured ICP and AP at 1 hour and 2 weeks after transplantation. PKH26-labelled MSCs were used for tracking the transplanted MSCs. To investigate the expression levels of glia cell derived neurotrophic factor (GDNF) and neurturin mRNA in the major pelvic ganglia (MPG), we performed real-time quantitative RT-PCR.ResultsThe reduction of ICP/AP and ICP-AUC in the MSC group was significantly lower than in the DMEM group (P<0.05; P<0.05) at 1 h. The ICP/AP and ICP-AUC at 2 weeks post-injury in the MSC group was significantly higher than in the DMEM group (P<0.01; P<0.05). The preloaded PKH26-labelled MSCs were detected in the MPG and CN using confocal microscopy indicating homing of the cells to the injured nerve and ganglia. GDNF and neurturin, which are important neurotrophic factors for erection, had expression levels in MPG significantly higher in the MSC group than in the DMEM group (P<0.01; P<0.05).ConclusionsIntravenous preload of MSCs before a CN injury may prevent or reduce experimental ED.

Nerve-sparing prostatectomy benefits men with poor preoperative erectile dysfunction

The aim of the study was to determine whether cavernous nerve preservation in men with prostate cancer and preoperative poor erectile function is a worthwhile endeavor. This is a retrospective analysis of prospectively collected data of 1,160 patients comparing erectile function pre- and postoperatively with 2 years of follow-up. Sexual Health Inventory for Men–International Index of Erectile Function 5 (SHIM-IIEF-5) questionnaire was used for assessment of erectile dysfunction preoperatively and at 6, 12, and 24 months postoperatively. IIEF < 13 was considered for inclusion. Bilateral nerve-sparing (BNS, n = 33) versus non-nerve-sparing (NNS, n = 32) procedures were compared. Continence data was collected. All men were offered penile rehabilitation therapy. Average preoperative IIEF-5 scores were 5.45 (BNS) and 4.28 (NNS) and not statistically significant. At 2 years, the average post-op IIEF scores were 4.91 (BNS) and 2.06 (NNS). This was a statistically significant decline in the NNS group. Most erectile function was recovered by 1 year. Positive surgical margins were not statistically significant between groups. Continence was improved in the BNS group (78 vs. 50 %, p = 0.047). Nerve sparing appears to be a worthwhile endeavor in men with poor preoperative IIEF as they return to baseline, oncologic outcomes are not compromised, and may have a continence benefit. The decision for an NNS procedure should not be made on the patient’s preoperative erectile function, but on the merits of other indicators such as grade or advanced clinical stage.

Baseline Erectile Function Alters the Cavernous Nerve Quantity and Distribution Around the Prostate

We clarified the distribution of neuronal nitric oxide synthase positive nerve fibers around the prostate and factors contributing to fiber quantity. We investigated 46 hemispheres of 23 nonnerve sparing radical prostatectomy specimens from patients with available preoperative International Index of Erectile Function and maximum penile circumferential change data. We performed immunohistochemical staining with neuronal nitric oxide synthase antibody, and divided the prostatic hemisphere into 6 zones to assess the distribution of neuronal nitric oxide synthase positive nerve fibers at the apex, midportion and base of the prostate. Multivariate analysis of the quantity of overall neuronal nitric oxide synthase positive nerve fibers used the variables of specimen weight, patient age, body mass index, International Index of Erectile Function and maximum penile circumferential change. A maximum penile circumferential change of 20 mm or less was considered objective erectile dysfunction. Median patient age was 68 years (range 57 to 74). Median International Index of Erectile Function-erectile function domain score was 12 (range 0 to 24) and median maximum penile circumferential change was 25.0 mm (range 2.70 to 38.3). Of the neuronal nitric oxide synthase positive nerve fibers 65% were distributed in a 3 to 5 o'clock sextant (p <0.001). Logistic regression analysis revealed that maximum penile circumferential change was the single significant variable (p = 0.019). The fiber count was greater in the objective erectile dysfunction group (median 1,500, range 382 to 2,760) than in the nonerectile dysfunction group (median 649, range 156 to 2,916) (p = 0.009). The fiber count was significantly different between the 2 groups in the 3 to 6 o'clock area, especially at the apex. Baseline erectile function greatly impacts cavernous nerve quantity and distribution. Cavernous nerve preservation in the neurovascular bundle, especially at the apex, is still essential for patients with erectile dysfunction.

701 THE IMPACT OF ERECTILE FUNCTION ON THE CAVERNOUS NERVE QUANTITY IN THE RADICAL PROSTATECTOMY SPECIMEN

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Basic Research I1 Apr 2010701 THE IMPACT OF ERECTILE FUNCTION ON THE CAVERNOUS NERVE QUANTITY IN THE RADICAL PROSTATECTOMY SPECIMEN Shin-ichi Hisasue, Kohei Hashimoto, Ryoji Furuya, Motoi Takeuchi, Youki Kyoda, Toshihiro Maeda, Ko Kobayashi, Toshiaki Tanaka, Koji Ichihara, Ryuichi Kato, Hiroshi Kitamura, Satoshi Takahashi, Naoya Masumori, and Taiji Tsukamoto Shin-ichi HisasueShin-ichi Hisasue More articles by this author , Kohei HashimotoKohei Hashimoto More articles by this author , Ryoji FuruyaRyoji Furuya More articles by this author , Motoi TakeuchiMotoi Takeuchi More articles by this author , Youki KyodaYouki Kyoda More articles by this author , Toshihiro MaedaToshihiro Maeda More articles by this author , Ko KobayashiKo Kobayashi More articles by this author , Toshiaki TanakaToshiaki Tanaka More articles by this author , Koji IchiharaKoji Ichihara More articles by this author , Ryuichi KatoRyuichi Kato More articles by this author , Hiroshi KitamuraHiroshi Kitamura More articles by this author , Satoshi TakahashiSatoshi Takahashi More articles by this author , Naoya MasumoriNaoya Masumori More articles by this author , and Taiji TsukamotoTaiji Tsukamoto More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1142AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Recent reports suggested that the nerve fiber outside of the neurovascular bundle (NVB) also plays an important role in erectile function following radical prostatectomy. However, there is no study investigating the factor contributing to the distribution of the cavernous nerve in human. We explored the distribution of nNOS-positive nerve fiber around the prostate and the contributing factors to the fiber quantity. METHODS We investigated 46 hemispheres of 23 non-nerve-sparing radical prostatectomy specimens. We analyzed the preoperative IIEF5 score and maximum penile circumferential change (MPCC) during a night. We divided prostatic hemisphere into 6 parts; 0-1, 1-2, 2-3, 3-4, 4-5, and 5-6 o'clock at apex, middle, and base of prostate respectively. We conducted the multivariate analysis to investigate the factors contributing to the overall nNOS-positive nerve fiber quantity using the variables including specimen weight, age, BMI, IIEF5 score > 17, and MPCC > 20mm. MPCC ≤ 20mm was considered as objective erectile dysfunction (ED). RESULTS Median age was 68 years (57-74). Median IIEF5 score was 12 (0-24) and median MPCC was 25.0 mm (2.70-38.3). The median number of the overall nNOS-positive nerve fibers around the prostatic hemisphere was 866 (156-2916). The distribution of nNOS-positive nerve fiber was 2.7% in 0-1, 6.4% in 1-2, 13.1% in 2-3, 30.4% in 3-4, 35.0% in 4-5, and 12.4% in 5-6 o'clock. Approximately, 65 % of fibers distributed in 3-5 o'clock of NVB area (p<0.001). Logistic regression analysis revealed that the MPCC was the single significant variable (p=0.027, OR 6.22, 95%CI 1.23-31.40). The fiber count was greater in the objective ED group (1500: 382-2760), than in the non-ED group (649: 156-2916) (p=0.009). The significant difference in the fiber count between 2 groups was seen in 3-6 o'clock, especially at apex (Fig). CONCLUSIONS This is the first report suggesting that the baseline erectile function impacts on the cavernous nerve fiber quantity. The current result suggested that cavernous nerve preservation around NVB at apex is still important, especially for the ED patients. Sapporo, Japan© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e273-e274 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Shin-ichi Hisasue More articles by this author Kohei Hashimoto More articles by this author Ryoji Furuya More articles by this author Motoi Takeuchi More articles by this author Youki Kyoda More articles by this author Toshihiro Maeda More articles by this author Ko Kobayashi More articles by this author Toshiaki Tanaka More articles by this author Koji Ichihara More articles by this author Ryuichi Kato More articles by this author Hiroshi Kitamura More articles by this author Satoshi Takahashi More articles by this author Naoya Masumori More articles by this author Taiji Tsukamoto More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Préservation neurologique et vasculaire au cours de la prostatectomie totale laparoscopique

The objective of the cavernous nerve preservation is to avoid injury of the unmyelinated nerve fibers and arteries destined to the corpora cavernosa. Dissection anatomical plans could be inter or extra fascial allowing complete or partial neurovascular bundle preservation. The technique is chosen according to the carcinological evaluated risk and anatomical characteristics. Accessory pudendal arteries preservation must be performed when such an artery is identified in order to improve the chance of recovery of spontaneous erections.

Association of Surgeon Subjective Characterization of Nerve Sparing Quality With Potency Following Laparoscopic Radical Prostatectomy

We assessed whether a surgeon self-graded assessment of neurovascular bundle preservation quality predicted potency following laparoscopic radical prostatectomy. From April 2001 to January 2007 a total of 767 laparoscopic radical prostatectomies were performed by 2 surgeons who graded left and right neurovascular bundle sparing qualities on a scale of 0 to 5. The total number of nerves spared was also recorded. We defined a composite variable, the bilateral sum neurovascular bundle sparing score, to encode 1 independent variable (scale of 0 to 10) for analysis. Multivariate linear regression models were evaluated to assess the significance of the bilateral sum neurovascular bundle sparing score for predicting validated potency outcomes, controlling for significant clinical variables in preoperatively potent men (Sexual Health Inventory for Men 21 or greater). The bilateral sum neurovascular bundle sparing score based model was compared to a model based on the separate number of nerves spared. A total of 313 patients were preoperatively potent, of whom 226 (72%), 77 (25%) and 10 (3%) underwent bilateral, unilateral and no neurovascular bundle sparing, respectively. Of the men who underwent bilateral neurovascular bundle sparing 64.3% were engaging in intercourse by 1 year. Regression models indicated that the bilateral sum neurovascular bundle sparing score and the number of nerves spared were highly significant independent positive predictors of postoperative sexual function (p <0.001). The bilateral sum neurovascular bundle sparing score model provided differential prognostic information in the majority group that underwent bilateral nerve preservation. Other independently predictive variables were patient age at surgery, months since surgery and preoperative Sexual Health Inventory for Men 21 to 25 (each p <0.001). Cavernous nerve preservation during laparoscopic radical prostatectomy is not an all or none phenomenon. A surgeon subjective sense of neurovascular bundle sparing quality may aid in accurately characterizing the return of sexual function following laparoscopic radical prostatectomy. Partial nerve preservation may lead to an incremental improvement in the return of sexual function.

3-Year Actuarial Biochemical Recurrence-Free Survival Following Laparoscopic Radical Prostatectomy: Experience From a Tertiary Referral Center in the United States

We performed a prospective analysis of pathological and oncological outcomes following laparoscopic radical prostatectomy at a medical center in the United States. A total of 528 men underwent laparoscopic radical prostatectomy between April 2001 and August 2005. We excluded 4 open surgical conversions (0.8%) and 16 men (3.0%) without followup. The remaining 508 men had a mean preoperative prostate specific antigen of 6.0 ng/ml (range 0.3 to 27) and Gleason score of 6.3 (range 6 to 10). Stage was cT1b in 1 case (0.2%), cT1c in 350 (68.9%), cT2a in 135 (26.6%), cT2b in 21 (4.1%) and cT2c in 1 (0.2%). Of the patients 89% underwent cavernous nerve preservation. Biochemical recurrence was defined and timed at the first prostate specific antigen of 0.2 ng/ml or greater if at repeat testing it remained 0.2 ng/ml or greater. Mean followup was 13.2 months (median 12, range 2 to 52). Pathological stage was pT0N0/Nx in 2 men (0.4%), pT2N0/Nx in 414 (81.5%), pT3aN0/Nx in 72 (14.2%), pT3bN0/Nx in 17 (3.3%) and pT2-3N1 in 3 (0.6%). Positive margin rates increased with higher stage (8.2% in pT2 and 39.3% in pT3 cases, p <0.0001). Three-year actuarial biochemical recurrence-free survival was 98.2% for pT2N0/Nx and 78.7% for pT3N0/Nx/N1 disease (p <0.0001), and it was 94.5% overall. Multivariate analysis controlling for age, preoperative prostate specific antigen, postoperative Gleason score and stage, and margin status showed that only Gleason score (greater than vs less than 7) and stage (pT3 or any N1 vs pT2) predicted biochemical progression. Laparoscopic radical prostatectomy can provide excellent cancer control outcomes for clinically localized prostate cancer with high actuarial biochemical recurrence-free survival rates at 3 years.

Impact of unilateral interposition sural nerve graft on the recovery of sexual function after radical prostatectomy in Japanese men: A preliminary study

To determine the effect of an interposition nerve graft on sexual function after radical prostatectomy. This study includes 64 patients, without hormonal therapy, who underwent a radical prostatectomy and intraoperative electrophysiological confirmation of cavernous nerve preservation. Twelve patients underwent a unilateral interposition sural nerve graft (UNG) for the resected neurovascular bundle. Twenty-one and 31 patients underwent bilateral nerve-sparing (BNS) and unilateral nerve-sparing (UNS) surgery without a nerve graft, respectively. As the age of patients was significantly younger in the UNG group than in the other groups, age-matched analysis also was conducted. Sexual function, evaluated by a self-administered questionnaire using the University of California Los Angeles-Prostate Cancer Index, was compared statistically among the three groups. In the age-matched analysis, the postoperative sexual function (SXF) score of the UNG group showed an intermediate level of recovery between those of the BNS and UNS groups at 12 months and reached the same level as the score at 12 months of the BNS group at 18 months postoperatively. The difference in the SXF score between the UNG and UNS groups began to appear after 6 months postoperatively and increased steadily with time. However, the background factors, such as the baseline SXF score, the usage rate of phosphodiesterase 5 inhibitors, and the rate of comorbidities were different between the UNG and UNS groups. The difference of the SXF score between the UNG and UNS groups increased with time after 6 months postoperatively. However, it might be difficult at present to attribute a better recovery of the SXF score to the nerve graft because of the difference in the background factors between the groups.

Neuromodulatory Drugs in a Radical Pelvic Surgery Patient

Since the introduction of the nerve sparing prostatectomy by Dr. Patrick Walsh in 1983 it has been recognized in multiple analyses that cavernous nerve preservation is quantitatively related to the recovery of erectile function. It is well appreciated that both spontaneous and PDE5 inhibitor response is heavily predicated upon the nerve sparing status with bilateral nerve sparing patients faring better than unilateral nerve sparing patients. Besides cavernous nerve status, other factors identified by Rabbani in the Memorial Sloan Kettering analysis of predictors of erectile function recovery include preoperative erectile function and patient age. A number of authorities have suggested that postoperative alterations in erectile hemodynamics is important and there is evidence to suggest that accessory pudendal artery injury with postoperative arteriogenic arterial insufficiency may have a negative long term impact on erectile function. Likewise, structural damage leading to venous leak is a poor prognostic indicator. There is little data on the role of vascular comorbidities, however, most authorities believe that the presence and severity of vascular comorbities is likely to have a negative impact upon long term erectile function recovery. The term “never-sparing” essentially means that the surgeon, using his/her experience and expertise defines if the nerves are anatomically (macroscopically) intact. This may have less than perfect correlation with the function of the cavernous nerves on either side. While intra-operative nerve stimulation may help in this regard there are concerns about false positive and false

INTRAOPERATIVE ELECTROPHYSIOLOGICAL CONFIRMATION OF URINARY CONTINENCE AFTER RADICAL PROSTATECTOMY

To determine the actual effect of nerve sparing radical retropubic prostatectomy (RP) on postoperative urinary continence we used intraoperative electrophysiological testing to confirm functional preservation of the neurovascular bundle (NVB). A total of 85 patients undergoing RP for localized prostate cancer were studied. During RP NVB preservation was assessed macroanatomically. Electrophysiological testing was then performed to confirm NVB preservation. The NVB was electrostimulated and responses were observed by monitoring intracavernous or intraurethral pressure changes. All patients were classified into 3 groups according to the degree of nerve sparing, that is a bilateral nerve sparing group, a unilateral nerve sparing group and a nonnerve sparing group, based on macroanatomical assessment as well as on electrophysiological assessment. Postoperative continence in each group was then determined. Urinary continence at baseline, and 3 and 6 months postoperatively was studied using a self-administered questionnaire. With electrophysiological assessment 20.6% of macroanatomically determined NVB preservations were reclassified. Analysis of the data on groups classified accurately by electrophysiological testing showed that the bilateral nerve sparing group maintained postoperative urinary function significantly more than the unilateral nerve sparing and nonnerve sparing groups. However, when only macroanatomical assessment was considered, no significant difference among the groups was found in urinary function. Electrophysiological assessment revealed that bilateral NVB preservation contributes to early recovery of urinary continence after RP. Thus, intraoperative electrophysiological assessment is useful for predicting postoperative quality of life.

Intraoperative electrical stimulation of cavernous nerves with monitoring of intracorporeal pressure to confirm nerve sparing during radical prostatectomy: Early clinical results.

We performed intraoperative cavernous nerve stimulation with an intracavernous pressure (ICP) monitoring system to confirm nerve sparing during radical pelvic surgery and assessed the results. Nineteen cases of radical prostatectomy and three of radical cystoprostatectomy were examined. Electrical stimulation of the site where the neurovascular bundle (NVB) was determined to run was performed and changes in ICP were measured before and after prostate removal. Of the 22 patients, bilateral NVBs were preserved in six patients while unilateral NVB was preserved in 16. Before dissection, all NVBs examined exhibited positive responses (ICP changes of>5 mmHg) to nerve stimulation. After removal of the prostate, positive responses were observed in 22 (79%) of 28 macroanatomically preserved NVBs. Of 16 sides on which the NVB was not preserved, there were positive responses in five (31%). In these patients, some nerve fibers were macroscopically observed lateral to the original site of NVB. Finally, bilateral or unilateral nerve sparing was confirmed electrophysiologically in 20 (91%) of the 22 patients. Intraoperative stimulation of the NVB while monitoring ICP changes is a simple and reliable method of accurately evaluating the preservation of cavernous nerves. This system may provide further insight into the mechanism of postoperative erectile dysfunction.