James Anaissie

Impact of Number of Cycles of Collagenase Clostridium Histolyticum on Outcomes in Patients With Peyronie's Disease

OBJECTIVE To analyze the impact of the number of cycles of collagenase Clostridium histolyticum (CCH) intralesional injection therapy on outcomes to further characterize CCH therapy. METHODS We conducted a retrospective review of the records of all patients treated with CCH for Peyronie disease between April 2014 and March 2016. Collected variables included demographics, pre- and posttreatment sexual function, penile curvature, penile vascular findings, and treatment outcomes. RESULTS A total of 77 patients were included in the study, of which 41 (53%) completed 4 cycles of treatment, consisting of 8 total injections. For all-comers regardless of numbers of cycles, curvature improved from 58.2° (standard deviation = 17.9°, range = 30°-105°) pre-treatment to 41.0° (standard deviation = 17.0°, range = 0°-85°) posttreatment (P < .001). In a repeated measures model, penile curvature improved significantly following the first 3 cycles, but not the fourth. Patients who had a ≥20% final reduction in curvature had a significantly greater change in curvature following the first injection (-16.2° vs -5.8°, P < .001). CONCLUSION Intralesional CCH therapy is an effective minimally invasive treatment for Peyronie disease, although the therapeutic benefit may decline after the third cycle of treatment. Patients with ≥20% reduction in curvature at the conclusion of treatment documented a greater curvature improvement after the first cycle and received more cycles of CCH.

Current Perspectives on Stem Cell Therapy for Erectile Dysfunction

INTRODUCTION Erectile dysfunction (ED) is a common sexual disorder that affects the lives of millions of male patients and their partners. Various medical and surgical therapies exist, with the most common being oral intake of phosphodiesterase 5 inhibitors. One therapeutic strategy in preclinical development to treat ED is stem cell transplantation. AIM To examine the studies that have investigated stem cells for the treatment of ED. METHODS A literature review was performed through PubMed focusing on stem cells and ED. MAIN OUTCOME MEASURES An assessment of different types of stem cells and how they may be applied therapeutically in the treatment of ED. RESULTS The stem cell types that have been investigated for the treatment of ED include bone marrow-derived mesenchymal, adipose-derived, muscle-derived, testes, urine-derived, neural crest, and endothelial progenitor. Depending on the cell type, research has demonstrated that with transplantation, stem cells exert a paracrine effect on penile tissue, and can differentiate into smooth muscle, endothelium, and neurons. CONCLUSION Multiple stem cell lines are currently being studied for their potential to treat ED. To date, stem cells have proven safe and effective in both animal and human models of ED. More research is needed to understand their full therapeutic potential.

Survey of patient and partner satisfaction following collagenase Clostridium histolyticum treatment for Peyronie's disease

Intralesional injection of collagenase Clostridium histolyticum (CCH) is a minimally invasive, Food and Drug Administration‐approved, effective treatment for Peyronies disease (PD). To assess the satisfaction of patients and their female sexual partners (FSP) following CCH therapy for PD, we conducted a retrospective review of the records of all patients treated with CCH for PD between 04/2014 and 03/2016. Collected variables included demographics, pre‐ and post‐treatment sexual function, penile curvature, penile vascular findings, and treatment outcomes. Patients and their FSPs were subsequently contacted by telephone and queried regarding their ability to have intercourse and their satisfaction with treatment. A total of 24 couples responded to our questionnaire and constitute the subjects of this analysis. Patient and FSP satisfaction with treatment were 67% and 71%, respectively. Significant predictors of FSP satisfaction with treatment included recall of penile trauma during prior sexual intercourse, improved ability to have sexual intercourse following treatment, and absence of post‐procedural glans hypoesthesia. In conclusion, CCH imparts a significant benefit on a couples sexual health. Partner satisfaction with treatment is correlated with improved ability to have sexual intercourse and absence of patient glans hypoesthesia.

A review of surgical strategies for penile prosthesis implantation in patients with Peyronie’s disease

The introduction of the inflatable penile prosthesis (IPP) has revolutionized the treatment of patients with both Peyronie’s disease (PD) and erectile dysfunction (ED). A thorough literature review was performed in order to review the surgical strategies used to treat PD, using the PubMed online database with the keywords “penile prosthesis”, “surgical management” and “Peyronie’s disease”. Patient satisfaction rates of 72–100% and partner satisfaction rates of 89% have been reported in the literature, although strong preoperative education may be needed to prepare patients for risks such as penile shortening, seen in up to 54% of patients. Three-piece IPPs are most commonly used, and when comparing the two most popular models (AMS 700 CX vs. Coloplast Titan), no significant differences were seen in functional outcomes or patient satisfaction. Simple insertion of an IPP has been shown to resolve curvature in 33–90% of patients, but surgeons may often need to also utilize ancillary straightening procedures for residual curvatures. Manual modeling can correct residual curvature with an 86–100% success rate, but with a 4% risk of urethral injury. When the post-modeling residual curvature exceeds 30 degrees, a plaque-releasing incision or plication is recommended to further reduce curvature. Grafting is recommended if the resulting incisional defect is larger than two centimeters. Alternative straightening techniques such as plication prior to IPP insertion, endoscopic plaque resection, the “scratch technique” and bone saw plaque incision have also been described.

Collagenase Clostridium histolyticum in the treatment of Peyronie’s disease: patient selection and perspectives

The safety and efficacy of the use of collagenase Clostridium histolyticum (CCH) for the treatment of Peyronie’s disease has been confirmed over the past several years. However, identification of the ideal patient population for use of this treatment is not well established. Multiple studies have attempted to delineate various patient-specific factors that may predict response to treatment with CCH, with the intent of enhancing patient selection. To date, these include baseline curvature severity, duration of disease, disease phase at presentation, plaque calcification, baseline erectile function, plaque size, age, comorbid diabetes, previous penile trauma, responsiveness to first treatment cycle, baseline penile shortening or pain, prior treatment with intralesional injection, compliance with plaque modeling, and atypical curvature. In addition, other studies have sought to explore various aspects of treatment with CCH that may affect patient perspective of treatment. They have focused on patient-reported outcomes, female partner considerations, cost of treatment, and potential confounders of patient satisfaction. This review provides a summary and analysis of currently available literature on topics of patient selection and perspectives in regard to treatment of Peyronie’s disease with CCH.

Collagenase Clostridium Histolyticum for the Treatment of Peyronie’s Disease: A ‘Real World’ Clinical Perspective

The introduction of collagenase Clostridium histolyticum (CCH) as a treatment option for Peyronie’s disease (PD), defined as the abnormal formation of collagen on the tunica albuginea of the penis, has provided patients with a promising new conservative therapy. Studies have shown that CCH improves curvature by an average of 17°, and although patient and sexual partner satisfaction is high, the improvement has arguable clinical implications. Similarly, the efficacy and cost of CCH contrasts strongly with more invasive surgical management, and is further limited by rare, but serious, complications and several contraindications. The future of CCH involves well-designed trials analyzing the effects of CCH on patients who are currently not indicated for therapy, and the optimal amount of treatment for the most efficient treatment possible. CCH provides a promising treatment option for patients who do not desire invasive management, but need further trials to fully elucidate its treatment implications.

Collagenase Clostridium histolyticum for the pharmacological management of Peyronie's disease.

Peyronies disease (PD) is defined as the abnormal accumulation of connective tissue in the tunica albuginea of the penis, and is an ongoing physical and psychological challenge for thousands of Americans. In vitro studies in the 1950s uncovered the potential of collagenase Clostridium histolyticum (CCH) to disrupt the collagen-containing plaques in PD, and opened the door to more in-depth clinical trials. Results indicated that with multiple dosage cycles followed by plaque modeling, penile curvature can be corrected, on average, in up to 35% of cases, with the majority of patients achieving ≥ 25% improvement in penile curvature. Most studies also indicated an improvement in patient-reported symptoms from the Peyronies Disease Questionnaire. Adverse events from treatment with CCH included penile bruising, pain and edema, but most were mild to moderate in severity and usually resolved without intervention, suggesting that CCH is an effective and safe treatment for PD.

Clinical use of alprostadil topical cream in patients with erectile dysfunction: a review

Erectile dysfunction (ED) is a common and debilitating disorder seen in over 50% of men older than 70 years. Oral phosphodiesterase type 5 (PDE5) inhibitors are the mainstay of treatment for ED, but cannot be used by a significant subset of patients due to systemic side effects and drug–drug interactions. Second-line therapy may include intracavernosal therapies, but are associated with poor compliance due to their invasive nature. Alprostadil has a mechanism of action different from that of PDE5 inhibitors. Clinical trials have shown topical alprostadil cream to be effective, increasing the erectile function (EF) score of the International Index of EF by up to 13 points from baseline. It has also proven to be safe and well tolerated, with mild-to-moderate and transient treatment-related adverse events that are generally localized to the application site. Topical alprostadil cream is a safe and effective second-line therapy for ED, indicated for those who cannot tolerate, or are not satisfied with, oral PDE5 inhibitor therapy.

Pioglitazone’s beneficial effects on erectile function preservation after cavernosal nerve injury in the rat are negated by inhibition of the insulin-like growth factor-1 receptor: a preclinical study

To determine if the insulin-like growth factor-1 (IGF-1) pathway is involved in the improvement in erectile function recovery in rats after nerve crush injury treated with pioglitazone (Pio). Sprague-Dawley rats were divided into four groups. The first group received sham operation (n = 5). The second group underwent bilateral cavernous nerve injury (BCNI, n  = 7). The third group received BCNI and Pio treatment (BCNI  +  Pio, n = 7), whereas the fourth group underwent BCNI with Pio treatment and IGF-1 inhibition (BCNI  +  Pio  +  JB-1, n = 7). The IGF-1 receptor (IGF-1R) was inhibited by JB-1, a small molecular antagonist of the receptor. After 14 days of treatment, erectile function was measured via intracorporal pressure normalized to mean arterial pressure (ICP/MAP) and the major pelvic ganglion and cavernous nerve harvested for western blot and immunohistochemistry (IHC) of phosphorylated-IGF-1Rβ (p-IGF-1Rβ), phosphorylated-ERK1/2 (p-ERK1/2), and neuronal NOS (nNOS). BCNI  +  Pio animals exhibited improvements in ICP/MAP, similar to Sham animals, and BCNI  +  Pio  +  JB-1 rats demonstrated a reduced ICP/MAP similar to BCNI-only rats at all measured voltages. Western blot results showed upregulation of p-IGF-1Rβ was observed in the BCNI  +  Pio group. Low levels of p-ERK1/2 were seen in the JB-1-treated animals. The immunoblot results were supported by IHC findings. Intense IHC staining of nNOS was detected in the BCNI  +  Pio group. The group treated with JB-1 showed minimal protein expression of p-ERK1/2, nNOS, and p-IGF-1Rβ. Pio improves erectile function in rats undergoing BCNI via an IGF-1-mediated pathway.

Practice Patterns in the Diagnosis and Management of Hypogonadism: A Survey of Sexual Medicine Society of North America Members

OBJECTIVE To describe practice patterns in the diagnosis and treatment of hypogonadism, as the optimal approaches are controversial. Multiple therapeutic options are currently available for hypogonadal men and treatment patterns vary considerably. The safety of testosterone therapy (TTh) remains understudied. MATERIALS AND METHODS A 23-question survey regarding diagnosis and treatment of hypogonadism was sent to all members of the Sexual Medicine Society of North America. Subgroup analyses compared responses between sexual medicine fellows and non-fellows, as well as between academic and nonacademic physicians, using a chi-squared analysis. RESULTS A total of 101 responses were included for analysis. The most common cutoff value used to diagnose hypogonadism was 300 ng/dL (55%, range = 200-400 ng/dL), and 31% felt comfortable giving TTh to a symptomatic patient with normal serum testosterone levels. No respondents felt that TTh increased a cardiovascular event risk. Of those surveyed, 68% would prescribe TTh to a hypogonadal man with severe lower urinary tract symptoms, and 64% would offer TTh to a man with low-risk prostate cancer on active surveillance. Fellowship-trained physicians were more likely to prescribe TTh to a man with hypogonadism but normal serum testosterone (P = .038), but they differed in the types of therapy they would use for men with hypogonadism who wish to preserve or regain fertility. CONCLUSION Significant variety exists in the diagnosis and treatment of hypogonadism. The majority of physicians will only prescribe TTh in the setting of subnormal serum testosterone levels, despite the presence of symptoms. None of the surveyed physicians reported concern over the risk of cardiovascular events.