BCG invokes superior STING-mediated innate immune response over radiotherapy in a carcinogen murine model of urothelial cancer.

Radiation and bacillus Calmette-Guérin (BCG) instillations are used clinically for treatment of urothelial carcinoma, but the precise mechanisms by which they activate an immune response remain elusive. The role of the cGAS-STING pathway has been implicated in both BCG and radiation-induced immune response; however, comparison of STING pathway molecules and the immune landscape following treatment in urothelial carcinoma has not been performed. We therefore comprehensively analyzed the local immune response in the bladder tumor microenvironment following radiotherapy and BCG instillations in a well-established spontaneous murine model of urothelial carcinoma to provide insight into activation of STING-mediated immune response. Mice were exposed to the oral carcinogen, BBN, for 12 weeks prior to treatment with a single 15 Gy dose of radiation or three intravesical instillations of BCG (1 × 108 CFU). At sacrifice, tumors were staged by a urologic pathologist and effects of therapy on the immune microenvironment were measured using the NanoString Myeloid Innate Immunity Panel and immunohistochemistry. Clinical relevance was established by measuring immune biomarker expression of cGAS and STING on a human tissue microarray consisting of BCG-treated non-muscle-invasive urothelial carcinomas. BCG instillations in the murine model elevated STING and downstream STING-induced interferon and pro-inflammatory molecules, intratumoral M1 macrophage and T-cell accumulation, and complete tumor eradication. In contrast, radiotherapy caused no changes in STING pathway or innate immune gene expression; rather, it induced M2 macrophage accumulation and elevated FoxP3 expression characteristic of immunosuppression. In human non-muscle-invasive bladder cancer, STING protein expression was elevated at baseline in patients who responded to BCG therapy and increased further after BCG therapy. Overall, these results show that STING pathway activation plays a key role in effective BCG-induced immune response and strongly indicate that the effects of BCG on the bladder cancer immune microenvironment are more beneficial than those induced by radiation. © 2021 The Pathological Society of Great Britain and Ireland.

Urethral bulking with native tissue during artificial urinary sphincter surgery.

The artificial urinary sphincter (AUS) is the "gold standard" surgical treatment for severe stress urinary incontinence.  However, a subset of patients with frail urethras may require technical adjuncts to ensure optimal cuff function.  Our objective is to provide a detailed tutorial of our institution's method for performing urethral bulking with native tissue in patients with frail urethras during AUS surgery. We have found that urethral bulking with native tissue provides a cost-efficient and durable technique for improved AUS cuff coaptation.  Our experience demonstrates adequate short and intermediate term efficacy with limited complications.  These techniques equip surgeons with an alternative surgical approach for appropriate patients receiving AUS surgery who have been previously exposed to pelvic radiation and/or significant surgical morbidity resulting in frail urethral tissue.

Medical treatment of recurrent ischaemic priapism: a review of current molecular therapeutics and a new clinical management paradigm.

OBJECTIVES: To examine the current molecular therapeutics in the medical treatment of recurrent ischemic priapism (RIP). To propose a stepwise clinical management paradigm for the treatment of RIP. METHODS: We performed a literature search using the PubMed database for the terms 'recurrent ischemic priapism' and 'stuttering priapism' up until December 2020. We assessed pre-clinical and clinical studies regarding medical management of RIP and molecular pathophysiology. Case series and randomized trials were evaluated by study quality and patient outcomes to determine a potential clinical management scheme. RESULTS: Recent research has fostered an improved understanding of the underlying molecular pathophysiology of RIP that has paved the way forward for developing new therapeutic agents. Medications targeting neurovascular, hormonal and haematological mechanisms associated with RIP show great promise towards remedying this condition. A host of therapeutic agents operating across different mechanistic directions may be implemented according to a clinical management scheme to potentially optimize RIP outcomes. CONCLUSION: RIP remains a medically neglected condition with current management focused on treating the acute condition rather than modulating the course of disease. Continued research into the molecular mechanisms of RIP and standardized clinical pathways can improve the quality of care for patients suffering from this condition.

Testicular ultrasound underestimates the size of small testicular masses: a radiologic-pathologic correlation study.

PURPOSE: Increasing use and resolution of testicular ultrasound imaging has resulted in a greater diagnosis of non-palpable small testicular masses and subsequent over-treatment with orchiectomy. Our aim was to determine the diagnostic accuracy of testicular ultrasound to accurately determine the pathologic size of small testicular masses (SMTMs) and to evaluate the association of various measurements with benign pathology. METHODS: Retrospectively, an institutional testicular cancer database was reviewed to evaluate the patients who underwent an orchiectomy for a testicular mass seen on ultrasound from 2003 to 2017. Three-dimensional measurements were compared from the ultrasound and pathology specimens, including other measures such as tumor volume and percentage of testicular volume. Finally, the predictive accuracy of maximum diameter and tumor volume to predict benign pathology was evaluated using receiver-operating curve analysis. RESULTS: We identified 208 patients and showed that ultrasound significantly underestimated sub-centimeter testicular masses (mean difference 0.56 cm, 95%CI 0.89-0.14, p = 0.004) and testicular masses between 1 and < 2 cm (mean difference 0.50 cm, 95%CI 0.97-0.15, p = 0.009). Tumor volume measured on ultrasound was consistently similar to pathologic tumor volume across all sizes and was significantly correlated (Spearman's Rho = 0.81). Mass volume had a greater predictive accuracy for benign pathology than maximum diameter using a 1 cm cut-off (AUC 0.65 vs 0.60). CONCLUSION: Using the maximal diameter, testicular ultrasound significantly miscalculated the pathologic dimensions of masses less than 2 cm compared to orchiectomy specimens. Volumetric measurements may better represent actual tumor sizes for SMTMs and may be a more useful measure for identifying those a higher risk for benign pathology, however, further studies are required.

Genetic testing in male infertility - reassessing screening thresholds.

PURPOSE OF REVIEW: Genetic testing in male infertility is an essential part of the process of diagnosis. Genetic abnormalities, such as Y-chromosome microdeletion, chromosomal abnormalities and mutations for cystic fibrosis, can all negatively impact a male's fertility and can be tested for during a fertility evaluation. Both Y-chromosome microdeletion and chromosomal abnormalities increase in prevalence as sperm concentrations decrease, and azoospermic men have the greatest frequency of genetic abnormalities. RECENT FINDINGS: These genetic abnormalities can also be found in oligospermic men; however, on the basis of several recent studies, the prevalence of genetic abnormalities is lower in oligospermic men than previously thought. SUMMARY: The current screening thresholds are devised from the previously determined prevalences and have not been revised based on the emerging data; thus, in this review of the literature, we will discuss this new evidence and whether screening thresholds should be changed.

Tubo-ovarian abscess: A potential mimicker of urachal malignancy.

Urachal cancer is a rare but aggressive malignancy. A urachal mass concerning for adenocarcinoma was identified in a 32-year-old G2P1 female on 12-week ultrasound and confirmed on pelvic MRI. Due to progressive growth of the mass and refractory abdominal pain, a multi-disciplinary meeting was held, after which the patient chose to undergo an exploratory laparotomy. A tubo-ovarian abscess was identified involving the intestine, right ovary, fallopian tube, and communicating with a patent, necrotic urachus. This is the first reported case of a tubo-ovarian abscess masquerading as a urachal malignancy, which can present similarly with abdominal pain and irritative urinary symptoms.

Postphalloplasty urinary function test: an observational study of novel outcome instrument to capture urinary dysfunction and quality of life after phalloplasty.

Due to growing social acceptance, there has been an increasing number of gender-affirmation surgeries performed in North America. Most research in this patient population focuses on surgical outcomes and advancing techniques. However, little work has been done to study functional outcomes. To better evaluate urinary dysfunction in the postphalloplasty trans men patient population, our group developed a novel patient-reported outcome instrument - the postphalloplasty urinary function test (PP UFT) and protocol to measure postvoid urethral volume (PVUR), and we present our preliminary results. We conducted a cross-sectional pilot study in a cohort of 15 adult trans men who had undergone phalloplasty with urethral lengthening surgery between 2018 and 2021. Patients had stable urinary function via the neophallus at the time of survey. Patients filled out the PP UFT and were asked to record their PVUR as per our protocol. The average PP UFT score was 8.9 out of 40 and the average quality-of-life (QOL) score was 2.6. Postvoid dribbling constituted the major complaint and on average comprised 63.2% of the reported PP UFT score. The average PVUR was 2.2 ml (range: 0.5-5.6 ml). There was a positive correlation between higher PP UFT and worse-reported quality of life (P < 0.01; R2 = 0.4). Current questionnaires accepted in cis-male urology have limitations for accurately capturing urinary dysfunction in this specific patient group. The combination of PP UFT and PVUR measurement offers potential for quantifying urinary function and quality of life in patients who undergo phalloplasty. Future studies will validate these instruments.

Advances in the selection of patients with prostate cancer for active surveillance.

Early identification and management of prostate cancer completely changed with the discovery of prostate-specific antigen. However, improved detection has also led to overdiagnosis and consequently overtreatment of patients with low-risk disease. Strategies for the management of patients using active surveillance - the monitoring of clinically insignificant disease until intervention is warranted - were developed in response to this issue. The success of this approach is critically dependent on the accurate selection of patients who are predicted to be at the lowest risk of prostate cancer mortality. The Epstein criteria for clinically insignificant prostate cancer were first published in 1994 and have been repeatedly validated for risk-stratification and selection for active surveillance over the past few decades. Current active surveillance programmes use modified criteria with 30-50% of patients receiving treatment at 10 years. Nonetheless, tools for prostate cancer diagnosis have continued to evolve with improvements in biopsy format and targeting, advances in imaging technologies such as multiparametric MRI, and the identification of serum-, tissue- and urine-based biomarkers. These advances have the potential to further improve the identification of men with low-risk disease who can be appropriately managed using active surveillance.

Acellular Dermal Matrix Tissues in Genitourinary Reconstructive Surgery: A Review of the Literature and Case Discussions.

INTRODUCTION: There have been major advancements in the field of urologic reconstruction and gender-affirming surgeries over the past 10 years. These operations have become increasingly complex involving multiple revisions, with limited healthy native tissue availability. Grafts are frequently needed when a patient's own tissue is expected to have poor wound-healing properties. To reduce the morbidity associated with autologous grafts and complications associated with synthetic grafts, acellular dermal matrices (ADMs) can be used as substitutes in genitourinary surgery as they demonstrate decreased immunogenicity and retaine structural integrity. OBJECTIVES: The purpose of this review is to describe the importance and potential uses of ADMs by reviewing the literature and highlighting key examples of our institution's expanded application of ADM grafts in genitourinary reconstruction. METHODS: We performed a literature review for the use of ADMs in genitourinary surgery including the search terms acellular dermal matrix, alloderm, extracellular matrix, penis, penile reconstruction, intrapenile prosthesis, phalloplasty, neophallus, urethroplasty, artificial urinary sphincters, Peyronie's disease, and urology. We highlight 5 representative genitourinary reconstructive cases performed at this institution where ADMs contributed to surgical success. Genitourinary reconstructive surgeries that have used ADMs in the literature included neophallus construction for gender affirmation, phalloplasty for trauma, penile augmentation, and plaque excision and grafting for Peyronie's disease. RESULTS: Biomechanical studies across different graft types are limited in genitourinary applications. Initial studies using ADMs indicate benefits of limited inflammatory response, finite elasticity, and substantial tensile strength, acceptably mimicking properties of the native tissue. CONCLUSION: Our experience and the current literature suggest that human ADM is a valuable option for tunica albuginea replacement, but its use to support free grafts should be cautioned secondary to graft take. Haney NM, Huang MM, Liu JL, et al. Acellular Dermal Matrix Tissues in Genitourinary Reconstructive Surgery: A Review of the Literature and Case Discussions. Sex Med Rev 2021;9;488-497.

Resident involvement in the prostatic urethral lift: implementing innovative technology in an academic setting.

Adoption of the prostatic urethral lift (PUL) as a treatment for benign prostatic hyperplasia highlights the importance of training residents with novel technology without compromising patient care. This study examines the effect of resident involvement during PUL on patient and procedural outcomes. Retrospective chart review was conducted on all consecutive PUL cases performed by a single academic urologist between October 2017 and November 2019. Trainees in post-graduate year (PGY) 1-3 are considered junior residents, while those in PGY 4-6 are senior residents. The International Prostate Symptom Score (IPSS) and quality of life (QOL) scores were used to measure outcomes. Simple and mixed-effects linear regression models were used to compare differences. There were 110 patients with a median age of 66.4 years. Residents were involved in 73 cases (66.4%), and senior residents were involved in 31 of those cases. Resident involvement was not associated with adverse perioperative outcomes with respect to the number of implants fired, the percentage of implants successfully placed, or the postoperative catheterization rate. After adjustment for confounding factors, junior residents were associated with significantly longer case length compared to the attending alone (+12.6 min, P = 0.003) but senior residents were not (+2.4 min, P = 0.59). IPSS and QOL scores were not significantly affected by resident involvement (P = 0.12 and P = 0.21, respectively). The presence of surgeons-in-training, particularly those in the early stages, prolongs PUL case length but does not appear to have an adverse impact on patient outcomes.

The Impact of Telemedicine on Sexual Medicine at a Major Academic Center During the COVID-19 Pandemic.

INTRODUCTION: Telemedicine has the potential to improve access to care; however, its utility in the field of sexual medicine remains in question. AIM: To examine the importance of video visits for the treatment of male sexual medicine at our academic center during the period of peak telemedicine use in April 2020. METHODS: We collected and compared deidentified data from all nonprocedure, adult outpatient encounters conducted as either office visits in April 2019 (n = 1,949) or video visits in April 2020 (n = 608). The primary International Classification of Diseases codes (ICD-10) labeled as diagnoses from all encounters were collected, with most encounters linked to several disease codes (n = 4,584). Demographic data were also collected. We performed comparative analyses on Stata (College Station, TX, USA) with significance set at α = .05. MAIN OUTCOME MEASURES: Disease codes were categorized based on their use and classification in urological care and the proportion that each category made up within the outpatient practice was calculated. RESULTS: In comparison to the office visits, which took place in April 2019, male sexual medicine visits in April 2020, during the peak of telemedicine use, made up a significantly larger overall share of our practice (P = .012), defined by relative rises in encounters pertaining to male hypogonadism, infertility, penile abnormalities, and testicular abnormalities. Outpatients seen over video visits were also younger than outpatients seen during the previous year over office visits (58.9 vs 60.8, P = .008). Further, race and ethnicity characteristics in the outpatient population were unaffected during the period of telemedicine use. CONCLUSIONS: During the period of historically high telemedicine use following the SARS-CoV-2 outbreak, encounters associated with male sexual medicine made up a significantly larger portion of our outpatient practice. Although the full influence of the COVID-19 pandemic cannot be delineated, our findings suggest telemedicine use is compatible with the field of sexual medicine. Rabinowitz MJ, Kohn TP, Ellimoottil C, et al. The Impact of Telemedicine on Sexual Medicine at a Major Academic Center During the COVID-19 Pandemic. Sex Med 2021;9:100366.

Immediate Artificial Urinary Sphincter (AUS) Reactivation at the Time of Urethral Cuff Exchange is Not Associated with Increased Erosion Rate.

OBJECTIVE: To retrospectively evaluate the outcomes of immediate artificial urinary sphincter (AUS) reactivation in patients after urethral cuff replacement. It is common practice to delay reactivation of an AUS for four to six weeks following surgery to replace a failed urethral cuff. This is due to concerns about local tissue edema risking obstruction and concerns for urethral erosion. Despite these concerns, there are no published data to support this practice. METHODS: Retrospective chart review of single surgeon procedures performed from 2005-2020. Patients with urethral cuff replacement for recurrent stress incontinence due to compression or mechanical failure were included. RESULTS: Thirty-four patients were identified who had immediate reactivation of the AUS following urethral cuff exchange. Thirty of these patients (88.2%) had radical prostatectomy and five patients also underwent further radiation therapy (14.7%). At 6 months follow-up, there was no reported events of erosion. Likewise, 32/34 (94%) of patients had no complications and reported expected urinary function of the AUS. Urinary retention was not observed. One patient required further re-exploration for a complication within his AUS system (2.9%), and another was ultimately unsatisfied with their unchanged baseline continence despite a fully functioning AUS (2.9%). CONCLUSION: In this series, we observe that immediate reactivation of the AUS after urethral cuff exchange is a safe and reasonable management approach. Limitations of this analysis include a single institution, retrospective study. However, early AUS reactivation after device revision has not been reported in the literature and warrants further investigation given the impact on patient quality of life.

Prostatic Urethral Lift in Patients With Obstructive Median Lobes: A Single Surgeon Experience at an Academic Center.

OBJECTIVE: To examine the long-term efficacy of prostatic urethral lift (PUL) for treating men, with or without an obstructive median lobe (OML), who suffer from lower urinary tract symptoms attributed to benign prostatic hyperplasia. MATERIALS AND METHODS: A retrospective review was performed on all consecutive PUL cases with or without OML from October 2017 to November 2019 by a single academic surgeon. Outcomes were measured using the International Prostate Symptoms Survey (IPSS) with quality of life (QoL) scores. Comparative testing and mixed-effects linear regression analysis were utilized with significance set at α = 0.05 and performed with Stata (College Station, TX). RESULTS: A total of 110 PUL procedures were performed on 106 patients (4 repeat surgeries) with a median age of 66.5 (interquartile range: 60.4-73.7). Twenty-three patients (21.7%) had an OML. Following PUL, patients in both groups showed significant improvements in IPSS (P <.001) and QoL (P <.001) scores. When stratifying by OML and controlling for confounding, IPSS scores in both groups displayed statistically significant improvement at follow-up visits, with no statistically significant intergroup difference (P = .32). The same held true for QoL improvements, with no statistically significant difference between groups (P = .18). The presence of an OML resulted in minimal effects on perioperative outcomes and complications but required significantly more implants (P = .008). CONCLUSION: PUL is a minimally invasive procedure effective at reducing lower urinary tract symptoms and improving the lives of men with benign prostatic hyperplasia without incurring risks of serious complications. These improvements were equivalent and upheld in patients who presented with OML.

Restorative Therapies for Erectile Dysfunction: Position Statement From the Sexual Medicine Society of North America (SMSNA).

INTRODUCTION: Current non-invasive treatments for erectile dysfunction (ED) include oral medications, intracavernosal injections, and vacuum-assisted devices. Though these therapies work well for many, a subset of patients have contraindications or are unsatisfied with these options. Restorative therapies for ED are a new frontier of treatments focused on regenerating diseased tissue and providing a potential "cure" for ED. AIM: The aim of this position statement is to examine existing clinical trial data for restorative therapies and identify elements that require further research before widespread adoption. METHODS: A literature review was performed to identify all clinical trials performed with regenerative therapy for ED. This includes treatments such as stem cell therapy (SCT), platelet rich plasma (PRP), and restorative related technologies like low-intensity shockwave therapy (LiSWT). MAIN OUTCOME MEASURES: Most clinical trials in restorative therapies were assessed for safety, feasibility, or efficacy. This included recording adverse events, changes in sexual function and erectile function questionnaires, and diagnostics measures. RESULTS: To date there is an absence of robust clinical data supporting the efficacy of restorative therapies regarding ED, though technologies such as LiSWT have established relative safety. CONCLUSIONS: Restorative therapies are a promising technology that represents a new frontier of treatment geared towards reversing disease pathology rather than just treating symptoms. However, current published clinical studies are limited. Future work needs to be adequately powered, multi-center, randomized, sham/placebo-controlled trials in well-characterized patient populations to ensure safety and demonstrate efficacy. Until these studies are done, restorative therapies should be reserved for clinical trials and not offered in routine clinical practice. Liu JL, Chu KY, Gabrielson AT, et al. Restorative Therapies for Erectile Dysfunction: Position Statement From the Sexual Medicine Society of North America (SMSNA). J Sex Med 2021;9:100343.

Penile fracture in a patient with Ehlers-Danlos syndrome: A case report.

The association of penile fracture with Ehlers-Danlos syndrome (EDS) has never been described. Our patient is a 41-year-old male with EDS who presented with a traumatic penile fracture, ten days following sexual intercourse. This report recognizes the possible heightened risk of structural penile injury in patients with connective tissue disorders such as EDS and emphasizes a need for a high index of suspicion of occult urethral injury and special considerations in surgical management of these complex cases.

Diagnosis of hemophilia in newborn circumcision: A case presentation.

Circumcision is often the earliest surgery performed in a young male's life. Though complications in this procedure are rare, prolong postoperative bleeding may be the first sign of undiagnosed hemophilia. Hemophilia is a rare X-linked bleeding disorder and if not treated prophylactically or promptly during surgical intervention can be fatal. In this case presentation we describe the diagnosis of hemophilia in a child presenting with postoperative bleeding from circumcision. We review the literature regarding the history of this disease with early surgery and highlight the current treatments.