Rectification of cavernosal fibrosis and veno-occlusive dysfunction by administration of suberoylanilide hydroxamic acid in a rat model of cavernosal nerve injury: Comparison with a PDE5 inhibitor.

BACKGROUND: Cavernosal fibrosis, which is induced by cavernosal nerve (CN) injury and progresses with time, is the main cause of cavernosal veno-occlusive dysfunction (CVOD) after radical prostatectomy. OBJECTIVES: To determine whether daily oral administration of suberoylanilide hydroxamic acid (SAHA; vorinostat) for 5-weeks from the immediate post-injury period after CN injury would rectify CVOD by suppressing cavernosal fibrosis and normalizing HDAC pathway in a rat model of CN crush injury (CNCI) and to compare the results with those obtained using chronic administration of PDE5-inhibitors (a positive control). METHODS: Fifty-six 12-week-old rats were randomized into the four groups: sham surgery (S), CNCI (I), and CNCI treated with daily administration of 25.0 mg/kg SAHA (V) or 20.0 mg/kg udenafil (P). Group-V and Group-P received the respective treatment for 5-weeks from the following day after CNCI. At 5 weeks after surgery, dynamic infusion cavernosometry (DIC), histological staining, and Western blot analysis were performed. RESULTS: Group-I had a significantly decreased papaverine response, higher maintenance rate or drop rate, lower smooth muscle (SM)/collagen ratio, decreased SM content, and increased protein expression of HDAC2, HDAC3, TGF-ß1, and collagen-1, compared with Group-S. The three DIC parameters in Group-V and Group-P significantly improved compared to those in Group-I. Except for the maintenance rate, the improvement in papaverine response and drop rate in Group-V was not significantly different from that in Group-P. Group-V and Group-P showed the rectification of SM/collagen ratio and protein expression of TGF-ß1 or collagen-1. SM content was improved in Group-P, but not in Group-V. Group-V showed the normalization of protein expression of both HDAC2 and HDAC3, whereas protein expression of only HDAC2 was partially restored in Group-P. DISCUSSION: Treatment strategies targeting the HDAC pathway might be helpful to alleviate CVOD induced by CN injury. CONCLUSIONS: According to our data, chronic administration of SAHA improves post-injury CVOD by suppressing cavernosal fibrosis via rectifying the HDAC/TGF-ß1 pathway in nerve-injured rats, comparable to that with PDE5 inhibitors.

Vessel-sparing Radiotherapy for Localized Prostate Cancer to Preserve Erectile Function: A Single-arm Phase 2 Trial.

BACKGROUND: Erectile dysfunction remains the most common side effect from radical treatment of localized prostate cancer. We hypothesized that the use of vessel-sparing radiotherapy, analogous to the functional anatomy approach of nerve-sparing radical prostatectomy (RP), would improve erectile function preservation while maintaining tumor control for men with localized prostate cancer. OBJECTIVE: To determine erectile function rates after vessel-sparing radiotherapy. DESIGN, SETTING, AND PARTICIPANTS: Men with localized prostate cancer were enrolled in a phase 2 single-arm trial (NCT02958787) at a single academic center. INTERVENTION: Patients received vessel-sparing radiotherapy utilizing a planning MRI and MRI-angiogram to delineate and avoid the erectile vasculature. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Both physician- and patient-reported inventories were used to capture erectile function at baseline and at 2 and 5 yr after treatment. Validated model-based comparisons were performed to compare vessel-sparing results to nerve-sparing RP and conventional radiotherapy. RESULTS AND LIMITATIONS: From 2001 to 2009, 135 men underwent vessel-sparing radiotherapy. After a planned interim analysis, the trial was stopped after meeting the primary endpoint. The median follow-up was 8.7 yr, with a ≥94% response rate to all inventories at each time point. At 5 yr, 88% of patients were sexually active with or without the use of sexual aids. The 2-yr erectile function rates were significantly improved with vessel-sparing radiotherapy (78%, 95% confidence interval [CI] 71-85%) compared to modeled rates for convention radiotherapy (42%, 95% CI 38-45%; p<0.001) or nerve-sparing prostatectomy (24%, 95% CI 22-27%; p<0.001). At 2 yr after treatment, 87% of baseline-potent men retained erections suitable for intercourse. The 5- and 10-yr rates of biochemical relapse-free survival were 99.3% and 89.9%, and at 5 yr the biochemical failures were limited to the National Comprehensive Cancer Network high-risk group. The single-arm design is a limitation. CONCLUSIONS: Vessel-sparing radiotherapy appears to more effectively preserve erectile function when compared to historical series and model-predicted outcomes following nerve-sparing RP or conventional radiotherapy, with maintenance of tumor control. This approach warrants independent validation. PATIENT SUMMARY: In this interim analysis we looked at using a novel approach to spare critical erectile structures to preserve erectile function after prostate cancer radiotherapy. We found that almost 90% of patients at 5 yr after treatment remained sexually active, significantly higher than previous studies with surgery or radiotherapy.

Vasculogenesis and Diabetic Erectile Dysfunction: How Relevant Is Glycemic Control?

Erectile dysfunction (ED) is a complication of diabetes, condition responsible for causing endothelial dysfunction (EDys) and hampering repair mechanisms. However, scarce information is available linking vasculogenesis mediated by Endothelial Progenitor Cells (EPCs) and diabetes-associated ED. Furthermore, it remains to be elucidated if glycemic control plays a role on EPCs functions, EPCs modulators, and penile vascular health. We evaluated the effects of diabetes and insulin therapy on bone marrow (BM) and circulating EPCs, testosterone, and systemic/penile Stromal Derived Factor-1 alpha (SDF-1α) expression. Male Wistar rats were divided into groups: age-matched controls, 8-weeks streptozotocin-induced type 1 diabetics, and insulin-treated 8-weeks diabetics. EPCs were identified by flow cytometry for CD34/CD133/VEGFR2/CXCR4 antigens. Systemic SDF-1α and testosterone levels were evaluated by ELISA. Penile SDF-1α protein expression was assessed, in experimental and human diabetic cavernosal samples, by immunohistochemical techniques. Diabetic animals presented a reduction of BM-derived EPCs and an increase in putative circulating endothelial cells (CECs) sloughed from vessels wall. These alterations were rescued by insulin therapy. In addition, glycemic control promoted an increase in systemic testosterone and SDF-1α levels, which were significantly decreased in animals with diabetes. SDF-1α protein expression was reduced in experimental and human cavernosal diabetic samples, an effect prevented by insulin in treated animals. Insulin administration rescued the effects of diabetes on BM function, CECs levels, testosterone, and plasmatic/penile SDF-1α protein expression. This emphasizes the importance of glycemic control in the prevention of diabetes-induced systemic and penile EDys, by the amelioration of endothelial damage, and increase in protective pathways. J. Cell. Biochem. 118: 82-91, 2017. © 2016 Wiley Periodicals, Inc.

Separate or combined treatments with daily sildenafil, molsidomine, or muscle-derived stem cells prevent erectile dysfunction in a rat model of cavernosal nerve damage.

INTRODUCTION: Long-term daily administration of phosphodiesterase type 5 (PDE5) inhibitors in the rat prevents or reverses corporal veno-occlusive dysfunction (CVOD) and smooth muscle cell (CSMC) loss and fibrosis, in both aging and bilateral cavernosal nerve resection (BCNR) models for erectile dysfunction. In the aging rat model, corporal implantation of skeletal muscle-derived stem cells (MDSC) reverses CVOD. Nitric oxide (NO) and cyclic guanosine monophosphate can modulate stem cell lineage. AIM: To investigate in the BCNR model the effects of sildenafil at lower doses, alone or in combination with MDSC or the NO donor molsidomine, on CVOD and the underlying corporal histopathology. MAIN OUTCOMES MEASURES: CVOD, histological, and biochemical markers in rat corporal tissue. Methods. Rats subjected to BCNR were maintained for 45 days either untreated, or received sildenafil in the water or retrolingually at 10, 2.5, and 1.25 mg/kg/day (medium, low, and very low doses), or intraperitoneal molsidomine, or MDSC implantation into the corpora cavernosa separately or in combination. Cavernosometry evaluated CVOD. Histopathology was assessed on penile sections by Masson trichrome, immunohistochemistry for α-smooth muscle actin (ASMA), or immunofluorescence for neuronal nitric oxide synthase (nNOS)/neurofilament 70, and in fresh tissue by Western blot for various markers and picrosirius red for collagen. RESULTS: All treatments normalized erectile function (drop rate), and most increased the CSMC/collagen ratio and ASMA expression in corporal tissue sections, and reduced collagen content in the penile shaft. MDSC also increased nNOS and brain-derived neurotrophic factor. The combination treatment was not superior to MDSC or sildenafil given alone, and upregulated PDE5. CONCLUSIONS: Lowering the dose of a continuous long-term sildenafil administration still maintained the prevention of CVOD in the BCNR rat previously observed, but it was less effective on the underlying histopathology. As in the aging rat model, MDSC also counteracted CVOD, but supplementation with very low-dose sildenafil did not improve the outcome.

[Primary and secondary prevention of erectile dysfunction]. / Primäre und sekundäre Prävention der erektilen Dysfunktion.

Erectile dysfunction has an incidence of up to 75% in men aged 80, thus making primary prevention really important. Aetiologically multiple reasons are responsible for erectile dysfunction; therefore, recommendations for primary prevention contain different parts. The first one is to maintain a healthy arterial system and prevent atherosclerosis. Besides that diabetes, neurogenic disturbances or mental distress should be avoided. Physical activity, balanced nutrition, nonsmoking, unsaturated fatty acids and moderate alcohol consumption are preventive. Regular erections cause oxygenation of the cavernous body and prevent fibrosis which could lead to an insufficient occlusion of the cavernous veins. If the patient already suffers from coronary heart disease or diabetes, blood pressure, pulse, blood lipids and blood sugar should be as normal as possible. Erectile dysfunction might be the primary symptom of coronary heart disease; therefore, consideration should be given to a cardiac examination in the diagnostic setting.

Penile haemodynamic changes in post-radical cystectomy patients.

The aim of this study was to assess the penile vascular changes in post-radical cystectomy patients. A prospective assessment took place between January 2003 and January 2005 of 45 potent men who underwent radical cystectomy and diversion for invasive bladder cancer. Nerve sparing (NS) technique was applied in 21 cases, while others were not subjected to NS (non-nerve sparing group; NNS = 24 cases). All patients were comparable in preoperative clinical and pathological parameters. A control arm was the preoperative normal indices of the same patients. Preoperative penile duplex ultrasounds (PDU) for all cases were carried out, and then follow-up 2, 6 and 12 months thereafter. On first postoperative visit, none of NS cases showed any arterial insufficiency, while two cases of NNS (8.3%) had peak systolic velocity (PSV) < 30 cm/sec. Moreover, all cases of both groups showed early increase of end diastolic velocity (EDV) > 5 cm/sec. In NS cystectomy group, the PSV showed statistically insignificant change [p > 0.05 (mean: 53.6, cm/sec)]. Shortly after surgery, the EDV values increased, followed by gradually significant improvement (decrease in EDV values) in comparison with control state (mean: 5.9 cm/sec). On the other hand, the NNS cases showed statistically insignificant changes in PSV (mean: 49.3 cm/sec), with deterioration in EDV that did not improve with time, in contrast to NS cases (mean: 13.15 cm/sec). The main significant penile vascular changes were in EDV (venogenic mechanism) in post-cystectomy patients. There was a gradual progressive improvement in venogenic competence mechanism in NS cases with insignificant deterioration of arteriogenic mechanism in both groups (NS/NNS).

The female factor: predicting compliance with a post-prostatectomy erectile preservation program.

INTRODUCTION: Early post-radical prostatectomy (RP) erectile preservation (EP) therapy may be critical to preserve erections after surgery. AIM: To assess if pre-RP female sexual function predicts of partner compliance with an EP protocol. MAIN OUTCOME MEASURES: Compliance, defined as use of localized penile EP therapy (intracavernosal injections [ICIs], vacuum erection device [VED], or alprostadil) at 3 and 6 months after RP. METHODS: Records of patients enrolled in our EP program from April 2007 to June 2008 were reviewed. Before surgery, patients completed the Sexual Health Inventory for Men (SHIM) and their female partners completed the Female Sexual Function Index (FSFI) questionnaire. Prior to surgery, patients were advised to take sildenafil 25 mg every nightly and use a 250-µg alprostadil suppository three times/week. At 1 month, additional daily use of a VED was encouraged. All patients unable to achieve erections sufficient for penetration were encouraged to initiate ICI of Trimix (phentolamine, papaverine, and PGE1) twice weekly after 3 months following surgery. Data were analyzed using binary logistic regression analysis holding all input variables constant. RESULTS: Twenty-nine patients had preoperative SHIM>7 and pre-RP partner FSFI data available. After a 4-week follow-up, compliance with alprostadil suppository declined and both ICI and VED usage increased. At 6 months, six (25.0%) patients had return of natural erectile function and 22 (91.7%) were achieving assisted erections. Higher preoperative partner FSFI scores were associated with greater compliance to the localized penile therapy component of our EP protocol (risk ratio 3.8, P=0.05). CONCLUSIONS: Preoperative female sexual function correlated with greater partner compliance with the localized component of our EP protocol. Consideration of a female partner's preoperative sexual function in predicting patient erectile function recovery after RP is warranted. Future studies are necessary to determine the clinical significance of this factor.

Effects of chronic red wine consumption on the expression of vascular endothelial growth factor, angiopoietin 1, angiopoietin 2, and its receptors in rat erectile tissue.

Long-term consumption of red wine (RW) apparently confers some protection against cardiovascular diseases due to antiatherosclerotic properties of polyphenols and ethanol (EtOH). There is some evidence indicating that they do so by regulating angiogenesis, but the mechanism and the modulator factors involved are largely unknown. The aim of this study was to evaluate the effects of chronic ingestion of RW in vascular structure and in the pattern of expression of vascular growth factors in the rat corpus cavernosum. Male Wistar rats aged 6 mo were treated with RW or an equivalent EtOH solution, as the only liquid source for 6 mo. Expression of vascular endothelial growth factor (VEGF), angiopoietin 1 and angiopoietin 2, and their receptors (VEGFR1, VEGFR2, and Tie2) in cavernous tissue was assayed by immunofluorescence and Western blotting. A reduction of VEGF and VEGFR2 expression, respectively, in smooth muscle and endothelial cells was observed in RW-treated animals, which was balanced by an increase in angiopoietins/Tie2 expression. In EtOH rats, only a decrease in expression of the receptors VEGFR2 and Tie2 was observed. These results, taken together, suggest that antioxidants present in RW activate selected mechanisms for the maintenance of cavernous tissue vascularization. However, functional studies will be necessary to elucidate if RW is of benefit in the prevention of deleterious vascular events associated with ED.

Long-term potency after early use of a vacuum erection device following radical prostatectomy.

OBJECTIVE: To evaluate the long-term potency after radical prostatectomy (RP) with the early use of a vacuum erection device (VED), and reasons for sexual inactivity and long-term attrition and maintenance of sexual activity, as RP is one of the most common treatments for prostate cancer but erectile dysfunction (ED) is a common side-effect. PATIENTS AND METHODS: We identified 141 sexually active patients who underwent RP at Cleveland Clinic Foundation. Patients were offered various non-oral treatment options to prevent ED and were also motivated for early penile rehabilitation. At 5 years 62% remained sexually active, of whom 71% had natural erections sufficient for intercourse without assistance, 8.5% were still using sildenafil, 10% were using combined therapy (sildenafil plus VED). At 5 years 38% (43/113) men were sexually inactive. The reasons included loss of interest in 17 (40%), cardiovascular/neurological diseases in 18 (42%), hormonal therapy in three (7%), loss of partner in three (7%) and two had other surgery. The natural rate of erections for sufficient vaginal penetration without an erection aid were preserved and maintained in the early-prophylaxis group, and almost 60% of them had used a VED as early prophylaxis. CONCLUSION: Despite current phosphodiesterase-5 inhibitor treatments for ED, VED is becoming recognized again as having a primary role in early penile rehabilitation in many patients, specifically those treated for prostate cancer.

Heart rate reduction with ivabradine improves erectile dysfunction in parallel to decrease in atherosclerotic plaque load in ApoE-knockout mice.

OBJECTIVE: To determine the effect of heart rate reduction with ivabradine on atherosclerotic lesions and erectile dysfunction. METHODS: Two different treatment regimes with ivabradine were applied in wild-type (C57/B6) and ApoE(-/-)-mice to study effects of ivabradine on erectile function and atherosclerosis in animals with and without present endothelial dysfunction. Preventive effects of ivabradine were evaluated in animals fed a high-cholesterol diet in parallel to treatment with ivabradine (orally via chow, 10 mg/kg per day). The other treatment regime started treatment with a high-cholesterol diet for 4 weeks to induce endothelial dysfunction. Thereafter, treatment with ivabradine (orally via chow, 15 mg/kg per day) was started in ApoE(-/-) mice for 3 months. Vital parameters were measured using the tail-cuff method. Erectile function was assessed by pharmacological stimulation of corpora cavernosa in organ bath chambers. Atherosclerotic plaque formation, oxidative stress, eNOS and collagen content were determined. RESULTS: Treatment with ivabradine significantly reduced heart rate (p<0.01), with no effect on blood pressure. Aortic atherosclerotic lesion size decreased with ivabradine in both treatment regimes (p<0.05). Endothelium-dependent relaxation of corpora cavernosa significantly decreased in ApoE(-/-)-mice with a restoration by ivabradine in prevention and reversal. Dihydroethidium-stained penile sections (p<0.05) and lipid peroxidase assay (p<0.05) revealed a reduction in superoxide production in ivabradine-treated animals. Penile eNOS-expression increased and collagen content significantly decreased (p<0.01) in ivabradine-treated animals. CONCLUSION: Ivabradine improves penile endothelial function by reduction of oxidative stress and penile fibrosis. Beneficial effects were achieved in prevention and manifest endothelial dysfunction.

Incidental prostate cancer at radical cystoprostatectomy: implications for apex-sparing surgery.

OBJECTIVE: To analyse retrospectively the clinicopathological features of incidental prostate cancer in patients undergoing radical cystoprostatovesiculectomy (RCP) for invasive bladder cancer, as recent studies suggest that prostatic apex-sparing surgery in patients undergoing RCP improves urinary continence and erectile function after surgery, but in those with incidental prostate cancer, leaving the apical region endangers the oncological outcome. PATIENTS AND METHODS: From 2004 to 2007, at our institution, 95 men had RCP for invasive bladder cancer. We reviewed their clinicopathological variables, especially apical involvement, and the course of prostate-specific antigen (PSA) levels before and after surgery. We compared clinically significant and insignificant prostate cancers. RESULTS: Of the 95 patients, 26 had incidental prostate cancer (mean age 68 years, range 53-80) on definitive histological examination. The mean (sd, range) preoperative PSA level in all 26 men was 3.6 (0.8, 0.2-14) ng/mL, but six of the 26 patients had preoperative PSA levels of >4 ng/mL and one other had suspicious findings on a digital rectal examination. Involvement of the apex was histologically confirmed in seven of the 26 patients (27%), including four with significant prostate cancer (P = 0.039). Preoperative PSA levels did not differ significantly between the seven patients with significant and 19 with insignificant prostate cancer, but seven patients with apical involvement had significantly higher PSA levels before RCP than the 19 who did not (P < 0.04). PSA levels after RCP remained below the limit of detection in all patients over a mean (range) follow-up 14.3 (3-32) months. CONCLUSION: In our series, preserving the apex of the prostate to decrease morbidity after RCP carried a 7.3% risk (seven of 95 patients) of leaving significant cancer in the residual prostatic tissue. No preoperative clinical value could exclude apical involvement. Therefore, our findings stress the oncological need for a careful and complete excision of the prostate during RCP.

Bicycle riding and erectile dysfunction: a review.

INTRODUCTION: For many years, reports in the literature have implicated bicycle riding as causing increased risk of erectile dysfunction (ED). Perineal compression during cycling has been associated with the development of sexual complications. AIM: To review current literature on the rationale for ED from bicycle riding and outcome of bicycle riding on erectile function and to present available research on preventative measures specifically regarding bicycle riding. METHODS: A systematic comprehensive literature review. RESULTS: There is a significant relationship between cycling-induced perineal compression leading to vascular, endothelial, and neurogenic dysfunction in men and the development of ED. Research on female bicyclists is very limited but indicates the same impairment as in male bicyclists. Preventative measures including use of a properly fitted bicycle, a riding style with a suitable seat position and an appropriate bicycle seat can help prevent impairment of erectile function. CONCLUSIONS: There is a need for further research on safe bicycle and bicycle seat design and investigations that address the underlying mechanisms leading to cycling-related sexual dysfunction in both male and female bicyclists.

Sacrifice of accessory pudendal arteries in normally potent men during robot-assisted radical prostatectomy does not impact potency.

AIM: Whether or not sacrificing accessory pudendal arteries (APAs) during radical prostatectomy affects potency has been an ongoing source of concern. Herein, we present our potency results relative to sacrificing APAs in normally pre-potent men following robot-assisted radical prostatectomy (RARP). METHODS: The distribution of APAs and clinical characteristics were prospectively recorded in 200 consecutive patients undergoing RARP with a cautery-free technique. Sexual function was assessed using the International Index of Erectile Function 5-item questionnaire (IIEF-5). All APAs were sacrificed due to stapling the dorsal vein complex. MAIN OUTCOME MEASURES: Postoperatively, potency was defined by an affirmative answer to the following two questions: "Were erections adequate for penetration?" and "were the erections satisfactory?" Postoperative IIEF-5 scores and quality of erections (% of preoperative firmness: 0%, 25%, 50%, 75%, 100%) were also obtained. Subgroup analysis of patients age < or =65 years with IIEF-5 score of 22-25 was performed. RESULTS: Eighty patients (40%) had APAs. Preoperatively, there was no association with having an APA and normal/abnormal sexual function. Preoperatively, 58/200 were < or =65 years with self-administered IIEF-5 scores of 22-25. Postoperatively, 53/58 (91%) were potent at 24 months follow-up. Nineteen of 58 patients had a sacrificed APA; 39 patients had no APA. Eighteen of 19 (95%) patients with sacrificed APAs were potent vs. 35/39 (90%) with no APA present (P = 0.53). Multivariate analysis showed no significant correlation between sacrificing an APA and time of potency recovery, quality of postoperative erections (94% vs. 90% P = 0.80) or mean IIEF-5 score (22.4 vs. 20.8, P = 0.13). CONCLUSION: We found no correlation between the presence or absence of APAs and preoperative sexual function. Furthermore, after sacrificing all APAs, we found no correlation with potency return, time to return of potency, quality of erections, or mean IIEF-5 scores at 24 months.

The timing of penile rehabilitation after bilateral nerve-sparing radical prostatectomy affects the recovery of erectile function.

OBJECTIVE: To define if erectile function (EF) outcomes were better in men with early institution of penile rehabilitation after radical prostatectomy (RP), as one of the mechanisms by which patients fail to recover EF after RP is collagenization of corporal smooth muscle with subsequent venous leak development, and rehabilitation is aimed at preventing these structural alterations. PATIENTS AND METHODS: The study population comprised patients who: (i) had clinically organ-confined prostate cancer; (ii) had fully functional erections, corroborated by the partner; (iii) had bilateral nerve-sparing RP; and (iv) committed to pharmacological penile rehabilitation. Patients completed the International Index of Erectile Function (IIEF) serially after RP. Patients were instructed to obtain three erections/week using initially sildenafil, and if unsuccessful, then intracavernous injections. Patients were subdivided into those starting rehabilitation at < 6 months after RP (early) and those starting at > or = 6 months after RP (delayed). RESULTS: There were 48 patients in the early group and 36 in the delayed group; patients in both groups were matched for age, comorbidity status and baseline EF. The mean duration after RP at the time of starting penile rehabilitation was 2 and 7 months in the early and delayed groups, respectively (P < 0.01). At 2 years after surgery there was a highly statistically significant difference in IIEF EF domain score between the early and delayed groups (22 vs 16, P < 0.001). There were also statistically significant differences between the groups in the percentage of men at 2 years after RP who had unassisted functional erections and sildenafil-assisted functional erections (58% vs 30%, P < 0.01; 86% vs 45%, P < 0.01, respectively). CONCLUSIONS: These data suggest that delaying the start of penile rehabilitation after RP is associated with poorer outcomes for EF.

Expression of vascular endothelial growth factor and angiopoietins in human corpus cavernosum.

OBJECTIVE: To evaluate the expression of the angiogenic factors vascular endothelial growth factor (VEGF) and angiopoietins (Ang) 1 and 2, in normal human penile erectile tissue. MATERIALS AND METHODS: Penile fragments were removed from four young healthy organ donors (aged 17-28 years), and processed for immunohistochemical studies for VEGF, Ang1 and Ang2, and their specific receptors (VEGFR1 and 2, and Tie2, respectively). Molecular analysis was used to confirm the expression of VEGF and Angs in erectile tissue. RESULTS: VEGF and VEGFR1 expression was restricted to smooth muscle cells (SMCs). VEGFR2 was detected mainly in the endothelium lining and to a lesser extent in the SMC. Ang1 had a scattered distribution mostly in the perivascular SM layer, showing co-localization with VEGF. Tie2 was faintly detected in the endothelial cells. Ang2 was not detected by immunohistochemical studies, but the use of the same antibody in molecular analysis confirmed Ang2 expression in human corpus cavernosum. CONCLUSIONS: We show for the first time the co-localization of VEGF and Ang1 in the SMC, suggesting an interaction for vessel stabilization. Ang2 seems to be available for neoangiogenesis, if challenged. Studies of endothelial markers, growth factors and specific receptors are useful for understanding vascular organization and angiogenesis in normal human erectile tissue. This knowledge will be fundamental for developing newer therapeutic approaches to prevent or even cure erectile dysfunction.

The systematic use of intraoperative vascular Doppler ultrasound during microsurgical subinguinal varicocelectomy improves precise identification and preservation of testicular blood supply.

OBJECTIVE: To evaluate the impact of systematic use of intraoperative Doppler ultrasound during microsurgical subinguinal varicocele repair. DESIGN: Prospective clinical study. SETTING: Andrology laboratory and male infertility section of the urology department of a tertiary care hospital. PATIENT(S): Two hundred and thirteen men with clinical varicocele. INTERVENTION(S): Subinguinal microsurgical varicocele ligation using an intraoperative vascular Doppler flow detector. MAIN OUTCOME MEASURE(S): Number of veins ligated, lymphatic spared, arteries identified or accidentally ligated. RESULT(S): A statistically significant greater number of arteries were identified and preserved when intraoperative vascular Doppler was used. In addition, the average number of internal spermatic veins ligated was statistically significantly greater in the same group. Accidental artery ligation occurred in two cases (1.1%) in which the Doppler was not applied. There was no statistically significant difference in number of lymphatics spared between groups. CONCLUSION(S): Our findings showed that concomitant use of intraoperative vascular Doppler during microsurgical varicocelectomy allows more arterial branches to be preserved, and more internal spermatic veins are likely to be ligated. This device should be considered an attractive tool to improve surgical outcomes and safety.

Retrospective analysis of the distance between the neurovascular bundle and prostate cancer foci in radical prostatectomy specimens: its clinical implication in nerve-sparing surgery.

OBJECTIVE: To analyse the distance between the ipsilateral neurovascular bundles (NVBs) and foci of prostate cancer (N-T distance) in specimens removed by radical prostatectomy (RP) and identify the predictor for N-T distance for preserving the ipsilateral NVB, as an accurate understanding of the anatomical relationship between prostate cancer foci and the NVB is necessary for establishing the indications for the appropriate use of nerve-sparing (NS) modifications of RP. PATIENTS AND METHODS: The study included 245 patients with prostate cancer who had RP through the perineal or retropubic approach between June 2000 and November 2006. The analysis focused on 302 foci of prostate cancer (192 cases), which involved at least the posterolateral region of the prostate. The N-T distance was separately measured in the apex, middle and base of the prostate, and was correlated with the maximum diameter and Gleason score of the foci, and the preoperative prostate-specific antigen (PSA) level. RESULTS: The mean N-T distance was 2.98, 2.95 and 3.03 mm in the apex (216 foci), middle (195 foci) and base (80 foci), respectively. In the apex, the N-T distance was related to both tumour size and preoperative PSA value (P < 0.001 and P < 0.05, respectively). In the base, tumour size was related to the N-T distance (P < 0.01), but the preoperative PSA level was not related to the N-T distance. In the middle, the association of tumour size with N-T distance was of borderline significance (P = 0.07). Irrespective of tumour location, the Gleason score did not contribute to the N-T distance. CONCLUSIONS: These findings show the basic information necessary when making a decision to perform NS-RP in patients with localized prostate cancer. The application of N-T distance could provide a better strategy for determining indications that warrant the use of NS RP than with the conventional tactile feedback approach.

Endovascular treatment of iliac aneurysm: Concurrent comparison of side branch endograft versus hypogastric exclusion.

OBJECTIVE: To analyze early and mid-term outcome of endovascular treatment in patients with iliac aneurysms, comparing the results of hypogastric revascularization by branch endografting with those of hypogastric occlusion. METHODS: Consecutive patients with iliac aneurysms receiving side branch endograft (Group I) were compared with those receiving endograft with hypogastric exclusion (Group II) during the interval from January 2000 to May 2008. Procedural details and outcomes were prospectively collected and were analyzed at one year to avoid mismatch in follow-up length. RESULTS: A total of 74 patients (mean age, 75.8 years, 95% males) were treated: 32 in Group I and 42 in Group II. No differences in baseline risk factors and aneurysm diameter (40.2 +/- 7.9 mm in Group I vs. 38.4 +/- 10.8 in Group II) were found. Concurrent treatment of aortic aneurysm was performed in 25/32 (78%) of Group I and 36/42 (86%) of Group II. Fluoro time was 48 minutes (interquartile range [IQR] 31-57) in Group I vs. 31 minutes (IQR 23-38) in Group II (P = .04). The amount of contrast was similar in both Groups: 184 ml (IQR 155-210) in Group I vs. 183 ml (IQR 155-200) in Group II. No intestinal ischemia or deaths occurred. There were no significant differences in failures of hypogastric side branch deployment (2/32) compared with hypogastric coiling (3/42). Limb occlusions all occurring in the external iliac artery side were 2/32 in Group I vs. 3/42 in Group II. Reintervention rates were similar (5/32 vs. 4/42) at one year. Shrinkage of 5 mm or more was detected in 7/23 (30%) of Group I and in 13/37 (34%) of Group II. Iliac endoleak was present in eight patients (19%) in Group II and in one patient in Group I (4%) (P = .1). Similarly, buttock claudication or impotence were more frequent after hypogastric exclusion, recorded in eight patients in Group II and in one patient in Group I (P = .1). CONCLUSIONS: Endovascular treatment of iliac aneurysm with hypogastric revascularization through side branched endografts is feasible and safe in the mid-term. When compared with hypogastric embolization, this option leads to similar technical success and reintervention rates. Endoleak and buttock claudication occur frequently in patients with iliac aneurysm treated with hypogastric exclusion, while are uncommon in those with hypogastric revascularization. Side branch endografting for iliac aneurysm may be considered a primary choice in younger, active patients with suitable anatomy, but larger studies and longer postoperative observation periods are needed.