Variability in Methodology of Erectile Dysfunction Regenerative Therapy Trials on ClinicalTrials.gov.

OBJECTIVE: To evaluate the variability in the criteria of erectile dysfunction (ED) regenerative therapy trials registered on ClinicalTrials.gov. METHODS: Interventional trials on ClinicalTrials.gov with the keywords "erectile dysfunction" and variations of "shockwave," "platelet rich plasma," "stem cell," "regenerative," and "restorative" were examined. Inclusion/exclusion criteria and primary/secondary outcomes were compared between extracorporeal shockwave therapy (ESWT), platelet rich plasma and stem cell injections (PRP/SC), and other regenerative therapies (ORT) groups. RESULTS: Of the 92 trials analyzed, International Index of Erectile Function (IIEF) score was the most common primary outcome (72%), with a higher prevalence in ESWT trials than PRP/SC or ORT trials (89% vs 44% and 58%, P <.001). Safety/tolerability was a primary outcome for 44% of PRP/SC trials and 25% of ORT trials but no ESWT trials (P <.001). ESWT trials more frequently had sexual/romantic relationship-based inclusion criteria and cancer treatment-related exclusion criteria than PRP/SC and ORT trials. CONCLUSION: There is substantial variability in the inclusion/exclusion criteria and outcome measures among ED regenerative therapy trials. ESWT trials most frequently utilized IIEF and had the strictest inclusion/exclusion criteria, suggesting more rigorous and functional outcome-based studies. Conversely, PRP/SC and ORT trials, but not ESWT trials, had safety/tolerability as a primary outcome, likely due to the experimental nature of these therapies. The variability in inclusion/exclusion criteria and outcome measures limits comparison of the various ED regenerative therapies.

The "Minimal-Touch" Technique for Artificial Urinary Sphincter Placement: Description and Outcomes.

OBJECTIVE: The study aimed to describe "minimal-touch" technique for primary artificial urinary sphincter placement and evaluate early device outcomes by comparing it with a historical cohort. MATERIALS AND METHODS: We identified patients who underwent primary artificial urinary sphincter placement at our institution from 1983 to 2020. Statistical analysis was performed to identify the rate of postoperative device infection in patients who underwent minimal touch versus those who underwent our traditional technique. RESULTS: 526/2601 total procedures (20%) were performed using our "minimal-touch" approach, including 271/1554 patients (17%) who underwent primary artificial urinary sphincter placement over the study period. Around 2.3% of patients experienced device infection after artificial urinary sphincter procedures. In the "minimal-touch" era, 3/526 patients (0.7%) experienced device infection, including 1/271 (0.4%) of those with primary artificial urinary sphincter placement. In comparison, 46/2075 patients (2.7%) experienced device infection using the historical approach, with 29/1283 (2.3%) of primary artificial urinary sphincter placements resulting in removal for infection. Notably, 90% of device infections occurred within the first 6 months after primary placement. The difference in cumulative incidence of device infections at 12 months did not meet our threshold for statistical significance for either the total cohort of all AUS procedures (primary and revision) or the sub-group of only those patients undergoing primary artificial urinary sphincter placement (Gray K-sample test; P=.13 and .21, respectively). CONCLUSION: The "minimal-touch" approach for artificial urinary sphincter placement represents an easy-to-implement modification with potential implications on device outcomes. While early results appear promising, longer-term follow-up with greater statistical power is needed to determine whether this approach will lower the infection risk.

Complications and troubleshooting in primary penile prosthetic surgery-a review.

Penile implant surgery is the gold standard to treat erectile dysfunction with success rates of over 90%. The first penile implants were developed in the early 1900s. Since then, several types of implants have been developed including malleable implants, two-piece inflatable implants, and three-piece inflatable implants. The three-piece inflatable penile prosthesis, which was introduced in 1973, is the most widely used type of penile implant in the United States. Penile implant surgery has undergone numerous advancements over the years, improving outcomes and patient satisfaction. However, as with any surgical procedure, there are risks and complications associated with penile implant surgery. It is important for surgeons to understand these potential complications and to have strategies in place to manage and prevent them to achieve the best possible outcomes for their patients.

Postoperative Opioid Prescribing Following Outpatient Male Urethral Surgery: Evidence for Change.

INTRODUCTION: Surgeons play a central role in the opioid epidemic. We aim to evaluate the efficacy of a standardized perioperative pain management pathway and postoperative opioid requirements in men undergoing outpatient anterior urethroplasty at our institution. METHODS: Patients undergoing outpatient anterior urethroplasty by a single surgeon from August 2017 to January 2021 were prospectively followed. Standardized nonopioid pathways were implemented based on location (penile vs bulbar) and need for buccal mucosa graft. A practice change in October 2018 transitioned (1) from oxycodone to tramadol, a weak mu opioid receptor agonist, postoperatively and (2) from 0.25% bupivacaine to liposomal bupivacaine intraoperatively. Postoperative validated questionnaires included 72-hour pain level (Likert 0-10), pain management satisfaction (Likert 1-6), and opioid consumption. RESULTS: A total of 116 eligible men underwent outpatient anterior urethroplasty during the study period. One-third of patients did not use opioids postoperatively, and nearly 78% of patients used ≤5 tablets. The median number of unused tablets was 8 (IQR 5-10). The only predictor for use of >5 tablets was preoperative opioid use (75% vs 25%, P < .01). Overall, patients using tramadol postoperatively reported higher satisfaction (6 vs 5, P < .01) and greater percentages of pain reduction (80% vs 50%, P < .01) compared to those using oxycodone. CONCLUSIONS: For opioid-naïve men, 5 tablets or less of opioid medication with a nonopioid care pathway provides satisfactory pain control following outpatient urethral surgery without excessive overprescribing of narcotic medication. Overall, multimodal pain pathways and perioperative patient counseling should be optimized to further limit postoperative opioid prescribing.

Testicular Pain - Not Always What it Seems: A Cross-Sectional Assessment of Patients Presenting for Chronic Scrotal Content Pain at a Tertiary Care Center.

OBJECTIVE: To review historical and examination findings in patients presenting to a tertiary care center for evaluation of Chronic Scrotal Content Pain (CSCP) defined by persistent/bothersome pain present for > 3-months. METHODS: We performed a retrospective chart review of all patients presenting to our medical center for evaluation of CSCP. Pertinent information collected included historical data, physical examination findings, laboratory and imaging results, and treatments recommended by the assessing physician. The data was summarized to present a cross-sectional representation of patients presenting for CSCP. RESULTS: 110 patients were identified. 80 patients (73%) had seen at least one prior urologist. 26 patients (24%) had undergone a prior unsuccessful surgical intervention for CSCP. Reproducible tenderness was present in 67% of patients including testicular tenderness in 50 (45%), epididymal tenderness in 60 (55%), and spermatic cord tenderness in 31 patients (28%). 33% of patients did not have any reproductible scrotal content tenderness on physical examination. Surgery was recommended in 57/110 patients (52%), including microdenervation in 22%. Musculoskeletal etiologies were suspected based on specific aspects of the history and physical examination in 43 patients (39%), prompting additional evaluation and/or referrals. CONCLUSION: CSCP presents with a wide array of symptoms and many patients do not have reproducible findings on examination, suggesting alternative sources of pain such as referred pain from musculoskeletal causes. The history and physical examination should include assessments for concurrent abdominal, back, hip, and other genital/pelvic pain that may suggest alternative diagnoses and referrals for appropriate treatment.

Comparison of patient-reported outcomes after penile prosthesis placement in men with and without Peyronie's disease.

We evaluated outcomes in patients undergoing penile prothesis (PP) implantation for erectile dysfunction (ED) and concurrent Peyronie's Disease (PD). A clinician-developed survey to assess satisfaction was sent to 354 patients who underwent PP placement from 2012-2018 by a single-surgeon. Results were compared based on the presence or absence of concurrent PD. 79 patients completed the survey (response rate 22%), including 38 patients (48%) with concurrent ED and PD (ED/PD). Mean follow-up was 31 months (standard deviation 19). 87% felt their condition was "very much" or "much" improved. There was no significant difference in patient-reported overall satisfaction with their PP or satisfaction with current penile length/girth based on the presence or absence of PD. 87% of patients with PD were satisfied with their degree of penile straightening after PP plus or minus concurrent straightening maneuvers such as modeling, plication, or incision/grafting. Sub-group analyses were performed to evaluate outcomes in those with concurrent PD/ED who required plaque incision/grafting at the time of PP placement for more severe deformity (n = 19). 47% of these patients were dissatisfied with their current penile length, compared with only 16% of those patients with PD/ED who did not require grafting (p = 0.05). In conclusion, the presence of PD alone may not impact PP satisfaction, but patients with more severe baseline deformity who require incision/grafting may be less satisfied with outcomes including penile length.

A Consistent Lack of Consistency in Defining the Acute and Chronic Phases of Peyronie's Disease: A Review of the Contemporary Literature.

INTRODUCTION: Treatment recommendations for Peyronie's Disease (PD) differ based on whether a patient is in the acute/active versus chronic/stable phase of the disease, yet there are no agreed upon criteria for defining these clinical entities. OBJECTIVES: To review the criteria used to define acute and chronic phase PD in modern PD intervention studies METHODS: We performed a search engine review to identify indexed publications for PD intervention studies and review articles / meta-analyses from the year 2011-2020. Outcomes results were catalogued and summarized across articles. As a result of the substantial heterogeneity of outcome measures and follow-up intervals, meta-analytic techniques were not applied to the data analysis. RESULTS: We identified a total of 104 studies that met inclusion criteria and had available information for review (n = 79 primary intervention studies; n = 25 review articles/meta-analyses/guidelines). Among the queried studies, we were unable to identify a consensus with respect to the criteria used to define acute and chronic phases of PD. 33% of primary intervention studies did not specifically define their criteria for acute and chronic phase PD, despite referencing these populations as part of the inclusion criteria in many instances. Studies used heterogenous criteria including total symptom duration, duration of "stable" symptoms, and presence/absence of pain. CONCLUSION: Due to varying definitions across the literature, we were unable to create a standardized definition of acute and chronic phase Peyronie's in terms of time. Our findings emphasize the need for greater consensus in defining the treatment cohorts with future studies that assess treatment for men with PD. Piraino J, Chaudhray H, Ames K, et al. A Consistent Lack of Consistency in Defining the Acute and Chronic Phases of Peyronie's Disease: A Review of the Contemporary Literature. Sex Med Rev 2022;10:698-713.

A Critical Analysis of Reporting in Systematic Reviews and Meta-Analyses in the Peyronie's Disease Literature.

BACKGROUND: Despite an increasing number of publications on Peyronie's disease (PD), evidence-based clinical decision-making remains challenging due to the small number of well-designed clinical trials. AIM: To perform a critical analysis of reporting quality in PD systematic reviews (SR) and meta-analyses (MA). METHODS: Study protocol registration was performed on the Open Science Framework platform. In January 2021, a systematic electronic search of the Medline/PubMed, Embase, Ovid, Scopus, Joanne Briggs Institute, and Cochrane databases was performed. Search terms included "Peyronie's disease" and "systematic review OR meta-analysis OR meta-analysis." Eligibility criteria were English-language, relevance to PD and specification of "systematic review" or "meta-analysis" in the title or abstract. Oxford Center for Evidence-Based Medicine levels of evidence were used to classify original studies reviewed within each publication. Risk of bias was assessed using the ROBIS tool. Data were tabulated and reported as means with standard deviation, median with interquartile range and t-testing as appropriate. Strength of association between variables was calculated using Pearson correlation coefficient. Statistical analyses were performed on RStudio (version 1.4.1106). OUTCOMES: Outcomes included review type, level of evidence, authorship, journal, publication date, "A MeaSurement Tool to Assess systematic Reviews" (AMSTAR-2) score and "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA) score. RESULTS: From 1974 to 2021, 340 articles were identified. After review, 17 full length articles were included. Thirteen were SR, 2 MA and 2 was combined. Significant heterogeneity was seen in evidence level of included studies. There was median 54% adherence to AMSTAR-2 criteria and 74% adherence to PRISMA criteria. Overall AMSTAR-2 confidence rating was Critically Low in 11 of 17 studies. Correlation analysis revealed very high positive association between AMSTAR 2 and PRISMA adherence (+0.95). ROBIS revealed "High" concern regarding methods used to collect data and appraise 12/17 studies (71%), and "High" concern regarding synthesis and findings in 8 of 17 studies (47%). CLINICAL IMPLICATIONS: Many SR include markedly heterogenous levels of evidence and fail to meet accepted methodological criteria for reporting. STRENGTHS AND LIMITATIONS: Main strengths include extensive literature review and analysis of standardized study reporting. One limitation is that aggregate scoring of AMSTAR-2 and PRISMA is not intended as primary method of quality assessment; however effect was minimized by reporting critical domains, overall quality assessments and specifics on globally poorly reported domains. CONCLUSION: More high quality randomized controlled PD trials are necessary; SR and MA should focus on these studies alone. Bole R, Gottlich HC, Ziegelmann MJ, et al. A Critical Analysis of Reporting in Systematic Reviews and Meta-Analyses in the Peyronie's Disease Literature. J Sex Med 2022;19:629-640.

Surgical Correction of Adult Congenital Penile Curvature: A Systematic Review.

BACKGROUND: Congenital penile curvature (CPC) is corrected surgically by various corporoplasty or tunica albuginea plication techniques, but the optimal surgical approach is not well-defined. AIM: To provide a comprehensive evaluation of the published literature pertaining to outcomes with penile plication and corporoplasty techniques for surgical management of CPC. To determine if plication or corporoplasty offers superior outcomes in surgical correction of CPC. METHODS: A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Checklist. The following databases were queried from inception to March 18, 2020 to search for studies describing surgical treatment of CPC: Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus. OUTCOMES: Objective and subjective postoperative outcomes including penile straightening, shortening, penile sensory changes, and reoperation rates for both corporoplasty and tunica albuginea plication were summarized. RESULTS: Fifty-five articles comprising 2,956 patients with CPC who underwent a plication procedure (n = 1,375) or corporoplasty (n = 1,580) were included. The definition of "treatment success" varied widely and most often involved subjective patient reporting (22 studies; 40%) or objective assessment (15 studies; 27%). We considered curvature correction to be satisfactory if there was self-reported patient satisfaction or residual curvature after correction of <20˚. Reported rates of successful straightening ranged from 75 to 100% and 73 to 100% for plication and corporoplasty, respectively. A comprehensive and accurate assessment of surgical outcomes for CPC correction, such as satisfactory penile straightening, reoperation rates, glans sensory changes, and other complications was limited by significant inter-study heterogeneity with respect to the reporting of treatment outcomes. CLINICAL IMPLICATIONS: While both plication and corporoplasty appear to be safe and effective options in the treatment of CPC, definitive conclusions cannot be drawn with respect to treatment superiority due to low-quality study design, methodology flaws, and significant heterogeneity in reporting. STRENGTH & LIMITATIONS: This report represents the most comprehensive review of CPC surgical management. However, there is a significant lack of standardization in the reporting of treatment outcomes for CPC, thereby limiting the reliability of the published data summarization encompassed by our review. CONCLUSION: Both plication and corporoplasty demonstrate high success rates and relatively low complication rates in the treatment of CPC, albeit with low-level evidence available in most research publications. Robust comparison of the surgical techniques used to correct CPC is limited by significant variation in reporting methods used in the literature. C. J. Britton, F. A. Jefferson, B. L. Findlay, et al. Surgical Correction of Adult Congenital Penile Curvature: A Systematic Review. J Sex Med 2022;19:364-376.

Penile Prosthesis Implantation Combined With Grafting Techniques in Patients With Peyronie's Disease and Erectile Dysfunction: A Systematic Review.

INTRODUCTION: Penile prosthesis (PP) implantation combined with grafting techniques is indicated in patients with Peyronie's disease (PD) and erectile dysfunction (ED) nonresponsive to medical and conservative treatment that present with residual penile curvature greater than 30°, severe penile deformity or significant penile shortening. OBJECTIVES: To address the preoperative evaluation, the surgical procedure and the functional outcomes of grafting techniques combined with PP implantation in patients with PD and concomitant ED and to provide future perspectives on the matter. METHODS: We performed a systematic review of the literature based on the PRISMA statement (PROSPERO ID: CRD42021224517). Records were identified by searching Medline, Scopus, The Cochrane Library and Web of Science databases as well as sources of gray literature from inception to December 2020. The quality of all included records was assessed based on a modified version of the Newcastle-Ottawa Scale for cohort studies. RESULTS: A total of 935 patients with a mean age of 59.6 ± 9.2 years from 23 studies were included in this systematic review. All studies reported excellent short- and long-term postoperative results, as well as high satisfaction rates ranging from 80 to 100%. A mean increase of 2.7 ± 1.4 cm in penile length was observed. Among different grafting materials and different types of PP, no significant differences in terms of preoperative, perioperative and postoperative functional outcomes or complications were demonstrated. Still, the operative time was shorter in studies applying the collagen fleece TachoSil. CONCLUSIONS: PP implantation combined with grafting is a safe and highly effective surgical procedure in patients with PD and concomitant ED. All grafting materials provide similar beneficial outcomes, but TachoSil subsequently reduces the operative time and does not require suturing. Still, no definite conclusions can be drawn regarding the superiority of one grafting technique over the other, as randomized clinical trials are lacking. Sokolakis I, Pyrgidis N, Ziegelmann M, et al. Penile Prosthesis Implantation Combined With Grafting Techniques in Patients With Peyronie's Disease and Erectile Dysfunction: A Systematic Review. Sex Med Rev 2022;10:444-452.

A Contemporary Analysis of Ureteral Reconstruction 30-Day Morbidity Utilizing the National Surgical Quality Improvement Program Database: Comparison of Minimally Invasive vs Open Approaches.

Objectives: To characterize 30-day morbidity of upper ureteral reconstruction (UUR) and lower ureteral reconstruction (LUR) surgery by comparing open and minimally invasive surgery (MIS) approaches using a national surgical outcomes registry. Methods: The American College of Surgeons National Surgical Quality Improvement Program database was reviewed for patients who underwent UUR and LUR between 2007 and 2017. Primary endpoints included 30-day complications, transfusion, readmission, return to operating room (ROR), and prolonged postoperative length of stay (LOS). Multivariable logistic regression was performed to observe the association of MIS approach on 30-day outcomes. Results: Three thousand forty-two patients were identified with 2116 undergoing UUR and 926 undergoing LUR. Of 2116 patients undergoing UUR, 1733 (82%) were performed through an MIS approach. On multivariable analysis, open approach for UUR was associated with increased odds of any 30-day complication (odds ratio (OR) 1.6 [1.1-2.4]; p = 0.014), major complication (OR 1.8 [1.04-3.0]; p = 0.034), transfusion (OR 3.7 [1.2-11.5]; p = 0.025), ROR (OR 2.0 [1.0-3.9]; p = 0.047), and prolonged LOS (OR 5.4 [3.9-7.6]; p < 0.001). Of the 926 patients undergoing LUR, 458 (49%) were performed through an MIS approach. On multivariable analysis, open approach for LUR was associated with increased odds of any 30-day complication (OR 1.5 [1.1-2.1]; p = 0.028), minor complication (OR 1.7 [1.1-2.6]; p = 0.02), transfusion (OR 8.1 [2.7-23.7]; p < 0.001), and prolonged LOS (OR 4.2 [2.4-7.3]; p < 0.001). Conclusion: Utilization of a national surgical database revealed an open approach was associated with increased 30-day morbidity across multiple postoperative outcome measures. These findings suggest an MIS approach should be considered, when feasible, for upper and lower ureteral reconstruction.

A Consistent Lack of Consistency in Defining the Acute and Chronic Phases of Peyronie's Disease: A Review of the Contemporary Literature.

INTRODUCTION: Treatment recommendations for Peyronie's Disease (PD) differ based on whether a patient is in the acute/active versus chronic/stable phase of the disease, yet there are no agreed upon criteria for defining these clinical entities. OBJECTIVES: To review the criteria used to define acute and chronic phase PD in modern PD intervention studies. METHODS: We performed a search engine review to identify indexed publications for PD intervention studies and review articles / meta-analyses from the year 2011-2020. Outcomes results were catalogued and summarized across articles. As a result of the substantial heterogeneity of outcome measures and follow-up intervals, meta-analytic techniques were not applied to the data analysis. RESULTS: We identified a total of 104 studies that met inclusion criteria and had available information for review (n = 79 primary intervention studies; n = 25 review articles/meta-analyses/guidelines). Among the queried studies, we were unable to identify a consensus with respect to the criteria used to define acute and chronic phases of PD. 33% of primary intervention studies did not specifically define their criteria for acute and chronic phase PD, despite referencing these populations as part of the inclusion criteria in many instances. Studies used heterogenous criteria including total symptom duration, duration of "stable" symptoms, and presence/absence of pain. CONCLUSION: Due to varying definitions across the literature, we were unable to create a standardized definition of acute and chronic phase Peyronie's in terms of time. Our findings emphasize the need for greater consensus in defining the treatment cohorts with future studies that assess treatment for men with PD.

Incidence of Venous Thromboembolism and Safety of Perioperative Subcutaneous Heparin During Inflatable Penile Prosthesis Surgery.

OBJECTIVE: To identify the incidence of venous thromboembolism (VTE) risk factors, postoperative VTE, and to assess the morbidity of perioperative pharmacologic VTE prophylaxis in men undergoing inflatable penile prosthesis (IPP) surgery. METHODS: We retrospectively reviewed 215 patients undergoing IPP surgery between July 2017 and June 2019. Univariate and multivariate statistical analyzes were performed to assess pre-operative Caprini risk score and compare post-operative day 0 scrotal drain output, scrotal hematoma formation, and VTE in men who received subcutaneous heparin (SqH) vs those who did not receive SqH. RESULTS: Of 215 IPP patients, 84% were classified as high or highest risk for VTE utilizing the Caprini risk score. A total of 119 (55%) received perioperative SqH with or without additional anti-thrombotics. Post-operative day 0 scrotal drain output was higher in those who received SqH compared to those who did not receive SqH, 99.9 mL vs 75.6 mL, respectively (P = .001). Minor scrotal hematomas occurred in similar rates in patients who received perioperative SqH vs those who did not, 3.8% vs 6.3%, respectively (P = .38). Similar results were found on subgroup analysis when eliminating patients who received SqH concurrently with other anti-thrombotics. The overall rate of postoperative VTE was 0.9%. No post-operative infections occurred. CONCLUSION: Patients undergoing IPP surgery are at elevated risk for VTE. To our knowledge, this is the first study showing SqH use in the perioperative IPP surgery setting is safe when used in conjunction with a scrotal drain. Preoperative VTE risk stratification may be performed and can be used to guide clinical decision making regarding pharmacologic prophylaxis.

Testicular sperm extraction vs. ejaculated sperm use for nonazoospermic male factor infertility.

OBJECTIVE: To study the potential benefit of testicular sperm compared with ejaculated sperm for men with oligospermia. DESIGN: After exemption from institutional review board approval, we performed a retrospective cohort study using the Mayo Clinic Assisted Reproductive Technology database. SETTING: Single academic center. PATIENT(S): Couples with nonazoospermic male factor infertility (total motile sperm <25 million per ejaculate) undergoing intracytoplasmic sperm injection with sperm obtained by testicular sperm extraction (TESE) or ejaculated sperm between 2016 and 2019. INTERVENTION(S): In vitro fertilization, Intracytoplasmic sperm injection, TESE. MAIN OUTCOME MEASURE(S): The primary outcome was live birth rate. The secondary outcomes were fertilization rate, blastulation rate, pregnancy rate, and miscarriage rate. RESULT(S): Subjects in the two groups were similar in age, body mass index, and ovarian reserve. Baseline sperm parameters were similar in the two groups: total motile sperm (5.4 in the ejaculate sperm group vs. 3.6 million motile per ejaculate), except that baseline motility was higher in the group that used ejaculated sperm (40% vs. 29%). The total number of mature oocytes retrieved was similar in the two groups, but the use of TESE was associated with a 20% decrease in fertilization (60.0% vs. 80.6%) and half the number of blastocyst embryos (two vs. four) compared with ejaculated sperm. Compared with ejaculated sperm, use of TESE did not improve the miscarriage rate (11% vs. 9%) or the live birth rate (50.0% vs. 31.3%). CONCLUSION(S): Patients with male factor infertility and oligozoospermia did not have improved ICSI outcomes with the use of TESE samples compared with ejaculated sperm.