Philip S. Li

The Functional and Structural Consequences of Cavernous Nerve Injury are Ameliorated by Sildenafil Citrate

INTRODUCTION Radical prostatectomy (RP) is associated with erectile dysfunction (ED). A single, placebo-controlled, human study has assessed the effects of regular sildenafil use after RP and demonstrated an increased chance of preservation of preoperative erectile function. Aim. This study was undertaken to define the effects of such a regimen in an animal model. METHODS Using the cavernous nerve (CN) crush injury model, animals were divided into a number of groups: no CN injury (sham), bilateral CN injury exposed to either no sildenafil (control) or sildenafil at two doses (10 and 20 mg/kg) subcutaneously daily for three different durations (3, 10, 28 days). MAIN OUTCOME MEASURES At these time points, CN electrical stimulation was used to assess erectile function by mean intracavernosal pressure (ICP)/mean arterial pressure (MAP) ratio. For the structural analyses, whole rat penes were harvested. Staining for Massons trichrome was utilized to calculate the smooth muscle-collagen ratio. Immunohistochemical antibody staining was performed for endothelial (CD31 and eNOS) and neural (GAP43, NGF, and nNOS) factors and immunoblotting was performed to analyze the AKT/eNOS pathway. Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) assay was used for the assessment of apoptotic indices and the CN architecture was evaluated by transmission electron microscopy (TEM). RESULTS Erectile function was improved with sildenafil in a time- and dose-dependent fashion with maximization of erectile function recovery occurring with daily 20 mg/kg at the 28-day time point. Sildenafil use resulted in smooth muscle-collagen ratio protection and CD31 and eNOS expression preservation. Sildenafil reduced apoptotic indices significantly compared with control. Animals exposed to sildenafil had increased phosphorylation of akt and eNOS. Tem demonstrated distinct differences in architecture between control and sildenafil groups toward an increased amount of myelinized nerve fibers. CONCLUSIONS Sildenafil use in the CN crush injury model preserves erectile function that appears to be mediated predominantly through preservation of smooth muscle content and endothelial function as well as through reduction in apoptosis.

The Shang Ring device for adult male circumcision: a proof of concept study in Kenya.

Objective:To assess safety, preliminary efficacy, and acceptability of the Shang Ring, a novel disposable device for adult male circumcision in Kenya. Methods:Forty HIV-negative men were recruited in Homa Bay, Kenya. Circumcisions were performed by a trained physician or nurse working with 1 assistant. Follow-up was conducted at 2, 7, 9, 14, 21, 28, 35, and 42 days after circumcision. Rings were removed on day 7. Pain was assessed using a visual analog scale (VAS) (0 = no pain, 10 = worst possible). Men were interviewed at enrollment and on days 7 and 42. Results:All 40 procedures were completed successfully. Mean procedure and device removal times were 4.8 (SD ± 2.0) and 3.9 (SD ± 2.6) minutes, respectively. There were 6 mild adverse events, including 3 penile skin injuries, 2 cases of edema, and 1 infection; all resolved with conservative management. In addition, there were 3 partial ring detachments between days 2-7. None required treatment or early ring removal. Erections with the ring were well tolerated, with a mean pain score of 3.5 (SD ± 2.3). By day 2, 80% of men were back to work. At 42 days, all participants were very satisfied with their circumcision and would recommend the procedure to others. Conclusions:Our results demonstrate that the Shang Ring is safe for further study in Africa. Acceptability of the Shang Ring among participants was excellent. With short procedure times, less surgical skill required, and the ease with which it can be used by nonphysicians, the Shang Ring could facilitate rapid roll-out of male circumcision in sub-Saharan Africa.

Value of serum antisperm antibodies in diagnosing obstructive azoospermia.

PURPOSE The requisite presence of active spermatogenesis for antisperm antibody production may be useful in identifying obstructive azoospermia. The diagnostic performance of serum antisperm antibody was evaluated as a test for obstructive azoospermia. MATERIALS AND METHODS A total of 484 men with male infertility who had undergone antisperm antibody testing were evaluated. Demographic data, patient history, and followup were recorded. Obstruction was confirmed by surgical exploration. Sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios were calculated to quantify diagnostic performance. ROC curves were calculated and compared. RESULTS Of 484 men 272 possessed documented obstruction of the vas or epididymis and 212 had documented infertility without azoospermia. The obstructed group had significantly increased antisperm antibody levels compared to the nonobstructed group. IgG, IgA, and IgM were analyzed as diagnostic tests for obstruction. The AUC for IgG, IgA and IgM ROC curves was 0.92, 0.85 and 0.67, respectively. The AUC for serum IgG against sperm tails was 0.92, 0.87 against sperm heads and 0.79 against sperm midpieces. IgG demonstrated the highest sensitivity (85%) with a specificity of 97% (chi-square test p <0.01). IgA possessed the highest specificity (99%), positive predictive value (99%) and positive likelihood ratio (70.0). CONCLUSIONS The presence of serum antisperm antibody was highly accurate in predicting obstructive azoospermia, particularly after vasectomy. It can obviate the need for testis biopsy, the current but more invasive and costly gold standard of detection. This allows the surgeon to proceed directly to surgical reconstruction or sperm retrieval after a simple blood test.

Correlation of ultrasonographic and orchidometer measurements of testis volume in adults

A study from New York was aimed at determining the correlation between testicular volume measurements made with an orchidometer and with high‐resolution scrotal ultrasonography; the authors found that measurements made with the former strongly correlate with those from the latter.

The Acceptability and Safety of the Shang Ring for Adult Male Circumcision in Rakai, Uganda

Objectives:Medical male circumcision (MMC) is recommended for HIV prevention in men. We assessed the acceptability and safety of the Shang Ring device compared with those of the dorsal slit method. Methods:HIV-negative, uncircumcised men aged 18 years or older who requested free MMC services in rural Rakai, Uganda, were informed about the Shang Ring and dorsal slit procedures and offered a free choice of procedure. Men were followed at 7 days postoperatively to assess adverse events related to surgery and to remove the Shang Ring. Wound healing was assessed at 4 weeks postoperatively. Results:Six hundred twenty-one men were enrolled, of whom 508 (81.8%) chose the Shang Ring and 113 the dorsal slit. The Shang Ring was provided to 504 men, among whom there were 4 failures of Ring placement (0.8%) that required surgical hemostasis and wound closure. Five hundred men received the Shang Ring and postoperative surgery–related moderate adverse events were 1.0%, compared with 0.8% among dorsal slit recipients. Complete wound healing at 4 weeks was 84% with the Ring and 100% with the dorsal slit (P < 0001). Resumption of intercourse before 4 weeks was 7.0% with the Ring and 15.0% with the dorsal slit (P = 0.01.) The mean time for surgery was 6.1 minutes with the Ring and 17.7 minutes with the dorsal slit. The mean time for Ring removal was 2.2 minutes. Conclusions:The Shang Ring is highly acceptable and safe in this setting, and could improve the efficiency of MMC services. However, back-up surgical services are needed in cases of Ring placement failures.

Randomized Controlled Trial of the Shang Ring Versus Conventional Surgical Techniques for Adult Male Circumcision: Safety and Acceptability

Objective:To compare clinical profiles of Shang Ring versus conventional circumcisions. Design:Parallel group open-label randomized controlled trial with one-to-one allocations in 2 sites. Methods:We enrolled HIV-negative men aged 18–54 years in Homa Bay, Kenya, and Lusaka, Zambia and followed them at 2, 7, 14, 21, 28, 42, and 60 days after Shang Ring versus conventional circumcision. We compared the duration of surgery, postoperative pain using a visual analog scale, adverse events rates, time to complete wound healing by clinical assessment, participant acceptability, and provider preferences between circumcision groups. Results:We randomized 200 men to each group; 197 and 201 contributed to the Shang Ring and conventional surgery analyses, respectively. Adverse event rates were similar between groups. Pain scores at most time points were similar, however, the Shang Ring group reported higher scores for worst pain during erections (3.5 ± 1.9 vs. 2.3 ± 1.7; P < 0.001). Significantly more men were satisfied with the cosmetic appearance following Shang Ring male circumcision (MC), 95.7% versus 85.9% (P = 0.02) in Kenya, and 96.8% versus 71.3% (P < 0.01) in Zambia. Although median time to complete wound healing was 43 days in both groups, conventional circumcisions healed on average 5.2 days sooner (P < 0.001). Shang Ring procedures took one-third the time of conventional MC, 7 versus 20 minutes. All circumcision providers preferred the Shang Ring. Conclusions:Safety profiles of the 2 techniques were similar, all MC providers preferred the Shang Ring technique, and study participants preferred the Shang Rings cosmetic results. The Shang Ring should be considered for adult MC as programs scale-up.

Spermatogenesis in humans and its affecting factors.

Spermatogenesis is an extraordinary complex process. The differentiation of spermatogonia into spermatozoa requires the participation of several cell types, hormones, paracrine factors, genes and epigenetic regulators. Recent researches in animals and humans have furthered our understanding of the male gamete differentiation, and led to clinical tools for the better management of male infertility. There is still much to be learned about this intricate process. In this review, the critical steps of human spermatogenesis are discussed together with its main affecting factors.

Comparison of intussusception pull-through end-to-side and conventional end-to-side microsurgical vasoepididymostomy: prospective randomized controlled study in male wistar rats.

PURPOSE Vasoepididymostomy is a technically challenging and complex microsurgical procedure. Recently a new triangulation end-to-side microsurgical technique was reported that allows intussusception of the epididymal tubule into the vasal lumen, resulting in a higher clinical patency rate of 92% with shorter operative time in preliminary clinical studies. We performed a prospective controlled randomized study comparing the patency rate, postoperative sperm granuloma rate and operating time of conventional and intussusception end-to-side vasoepididymostomy in previously vasectomized rats. MATERIALS AND METHODS We randomized 42, 6-week-old male Wistar rats into 4 groups, including 6 into the sham operation, and 12 each into the control, conventional end-to-side and intussusception end-to-side vasoepididymostomy groups. Bilateral 2-clip vasectomy was performed in all animals except those in the sham operation group. Bilateral intussusception or conventional end-to-side vasoepididymostomy was performed in the assigned animals 2 weeks after vasectomy. Animals in the control group underwent vasectomy only. In the sham operation group the testes were mobilized out of the scrotum and then returned. Rats were sacrificed at 8, 12, 16 and 24 weeks, respectively. The anastomosis and vasectomy sites were inspected for sperm granuloma. To assess patency the abdominal end of the vas was transected and intraluminal fluid was examined microscopically at 400x magnification for the presence of motile sperm. Patency was further confirmed by performing retrograde indigo carmine vasography through the anastomoses. RESULTS In the intussusception and conventional groups the patency rate was 91.7% and 54.2% (p = 0.004), the sperm granuloma rate was 20.8% and 58.4% (p = 0.035), and average operative time was 65.8 and 67.7 minutes (p = 0.197), respectively. CONCLUSIONS Intussusception end-to-side vasoepididymostomy is superior to conventional end-to-side vasoepididymostomy with respect to the patency and postoperative sperm granuloma rates. Further investigations are required to confirm such findings clinically in humans.

A decision analysis of treatments for nonobstructive azoospermia associated with varicocele.

OBJECTIVE To examine the economic impact of initial treatments for varicocele-associated nonobstructive azoospermia, specifically varicocelectomy versus microsurgical testicular sperm extraction (TESE) with IVF/intracytoplasmic sperm injection (ICSI). DESIGN Decision analytic model based on 1) outcomes data from Society for Assisted Reproductive Technology (SART) database and peer-reviewed literature and 2) costing data from Medicare Resource-Based Relative Value Scale and sampling of high volume US IVF centers. SETTING Academic medical center. PATIENT(S) Simulation with a decision analytic model. INTERVENTION(S) Variation of successful spontaneous live delivery after varicocelectomy versus rate of successful live delivery after IVF/ICSI. MAIN OUTCOME MEASURE(S) Cost-effectiveness. RESULT(S) Microsurgical TESE was more cost effective than varicocelectomy. In 1999, initial treatment with microsurgical TESE was more cost effective (

External spermatic sheath injection for vasal nerve block

65,515) than varicocelectomy (