Oncological and Functional Outcomes of Penile Shaft Sparing Surgery for Localised Penile Cancer: A Systematic Review.

CONTEXT: Penile shaft sparing (PSS) surgery for localised penile cancer (PeCa) aims to balance oncological and functional outcomes. OBJECTIVE: To summarise the published evidence on different PSS approaches. EVIDENCE ACQUISITION: We performed a systematic review adhering to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The systematic search was performed on PubMed, EMBASE, and Scopus databases up to February 14, 2023. The inclusion criteria encompassed retrospective or prospective studies including patients ≥18 yr of age with localised PeCa treated with different PSS approaches, classified as laser ablation, circumcision, wide local excision, glansectomy with or without split skin graft, glans resurfacing, and mixed technique excision. The risk of bias was assessed using the Newcastle-Ottawa scale. A quantitative synthesis was not performed due to anticipated data heterogeneity and a lack of comparative studies. EVIDENCE SYNTHESIS: Out of 4343 articles identified, 47 met our inclusion criteria, including 10 847 patients. The year of publication ranged between 1983 and 2021. Nine studies were prospective case series, while the remaining studies were retrospective. No comparative studies were identified. Most of the cases included in these studies were Ta and T1. The oncological outcomes were good for all the approaches, with cancer-specific mortality ranging between 0% and 18%. Sexual and cosmetic outcomes, despite being under-reported, were good for all the approaches, with almost all patients being satisfied with their quality of life after surgery. The Newcastle and Ottawa scale revealed a high or severely high risk of bias in all the included studies. CONCLUSIONS: PSS approaches were safe and had good functional outcomes, considering however the overall low quality of the studies on this issue. PATIENT SUMMARY: The perioperative, function, and oncological outcomes of penile shaft sparing approaches are good. However, high-quality studies are needed to determine whether these approaches benefit patients with localised penile cancer.

Therapeutic outcomes and analysis of Doppler findings in 25 patients with non-ischemic priapism.

Non-ischemic priapism (NiP) is painless partial tumescence caused by genital trauma and the formation of intracorporal arterio-venous fistula. This is a retrospective study of 25 men with NiP and reports the long-term erectile function and colour doppler ultrasound (CDUS) findings after treatment for NiP. Unstimulated CDUS was performed at diagnosis, 1 week and at last follow-up after treatment. CDUS traces were analysed: peak systolic velocity (PSV), end diastolic velocity (EDV), resistive index (RI) and mean velocity (MV) were calculated. Erectile function was assessed using the IIEF-EF questionnaire. At the last follow-up (median 24 months), 16 men had normal erectile function (64%): median IIEF-EF score 29 (IQR 28.5-30; σ2 2.78) and nine had erectile dysfunction (36%): median IIEF-EF score 17 (IQR 14-22; σ2 33.6). MV and EDV were statistically higher in those patients with erectile dysfunction at last follow-up compared to patients with normal erectile function: median MV 5.3 cm/s (IQR 2.4-10.5 cm/s; σ2 34) vs 2.95 cm/s (IQR 1.03-3.95; σ2 3.4) p < 0.002 and median EDV 4.0 cm/s (IQR 1.5-8.0; σ2 14.7) vs 0 cm/s (IQR 0-1.75; σ2 2.21) p < 0.004. Erectile dysfunction was observed in 36% of men treated for NiP and was associated with abnormal low resistance resting CDUS waveforms. Further investigation for persistent arteriovenous fistulation should be considered in these patients.

The Rho-kinase inhibitor Y27632 promotes ureteral relaxation in an in vivo rat model for partial ureteral obstruction.

PURPOSE: Aim of this study was to evaluate the effect of intravenous Y27632 (a ROK inhibitor) on intra-ureteral pressures and on blood pressure in an in vivo rat model for unilateral partial ureteral obstruction (PUO). METHODS: 15 Male Sprague Dawley rats were used. Under isofluran anesthesia, saline was continuously infused via polyethylene (PE)-10 catheters inserted in the ureters beneath the kidney pelvis. Left psoas muscle was sutured around the distal left ureter to create a partial obstruction. Carotid artery and femoral vein were cannulated with PE catheters for registration of mean arterial blood pressure (MAP) and for administration of drugs. Left and right ureter pressures and MAP were simultaneously recorded. Y27632 (0.03 and 0.1 mg/kg each n = 6-7) was given intravenously. T-test was used for comparisons. RESULTS: Spontaneous peristaltic pressure waves were recorded at baseline for both ureters. After the obstruction, Y27632 reduced maximum pressure (MaxP) by 10.5 ± 1.9% (0.03 mg/kg; p = 0.004) and 29.1 ± 4.8% (0.1 mg/kg; p < 0.001), minimum pressure (MinP) by 5.2 ± 2.3% (0.03 mg/kg; p = 0.02) and 12.2 ± 3.4% (0.1 mg/kg; p = 0.009), the area under the curve (AUC) by 7.8 ± 2.4% (0.03 mg/kg; p = 0.008) and 16.5 ± 3.7% (0.1 mg/kg;p = 0.007), the waves amplitude by 23.4 ± 11.3% (0.03 mg/kg; p = 0.098) and 38.7 ± 7.5% (0.1 mg/kg; p < 0.001), with no effect on contraction frequency. During simultaneous recordings from the normal ureter at the investigated doses, Y27632 reduced MaxP, MinP, AUC and waves amplitude by 1-7%. The MAP was reduced by 12.5 ± 5.3% (0.03 mg/kg; p = 0.07) and 15.8 ± 1.8% (0.1 mg/kg; p < 0.001). CONCLUSIONS: Y27632 decreased intra-ureteral pressures of a partially obstructed ureter with limited effect on blood pressure in an animal model of unilateral PUO.

European Society of Sexual Medicine consensus statement on the use of animal models for studying Peyronie's disease.

Introduction: Animal models are frequently used for translational research in Peyronie's disease (PD). However, due to lack of availability of guidelines, there is some heterogeneity in study design, data reporting, and outcome measures. Aim: This European Society for Sexual Medicine consensus statement aims to provide guidance in utilization of animal models in PD research in a standardized and uniform fashion. Methods: PubMed was searched for studies using animal models for PD. The following search terms were used: ("Peyronie's disease" OR "penile fibrosis" OR "penile curvature" OR "induration penis plastica" OR "erectile dysfunction") AND ("rodent" OR "mouse" OR "mice" OR "rat" OR "rabbit"). Outcomes: This European Society for Sexual Medicine statement describes best practice guidelines for utilization of animals in PD research: power calculation, details of available models, surgical procedures, and measurement techniques, while highlighting possible pitfalls and translational limitations of the models. Results: In total, 2490 studies were retrieved and 2446 articles were excluded. A total of 44 studies were included, of which 40 studies used rats, 1 study used both rats and mice, 1 study used a genetic mouse model, and 2 studies used rabbits. A significant number of the studies (70.5%) used transforming growth factor ß 1 for induction of fibrosis. Oxford 2011 Levels of Evidence criteria could not be applied due to the nature of the studies. Conclusion: Despite certain limitations of PD animal models presented, we aimed to provide guidance for their appropriate use in translational research, with the purpose of improving study quality and reproducibility as well as facilitating interpretation of reported results and conclusions.

Outcomes following radical inguinal lymphadenectomy for penile cancer using a fascial-sparing surgical technique.

PURPOSE: To describe our surgical technique and report the oncological outcomes and complication rates using a fascial-sparing radical inguinal lymphadenectomy (RILND) technique for penile cancer patients with cN+ disease in the inguinal lymph nodes. METHODS: Over a 10-year period, 660 fascial-sparing RILND procedures were performed in 421 patients across two specialist penile cancer centres. The technique used a subinguinal incision with an ellipse of skin excised over any palpable nodes. Identification and preservation of the Scarpa's and Camper's fascia was the first step. All superficial inguinal nodes were removed en bloc under this fascial layer with preservation of the subcutaneous veins and fascia lata. The saphenous vein was spared where possible. Patient characteristics, oncologic outcomes and perioperative morbidity were retrospectively collected and analysed. Kaplan-Meier curves estimated the cancer-specific survival (CSS) functions after the procedure. RESULTS: Median (interquartile range, IQR) follow-up was 28 (14-90) months. A median (IQR) number of 8.0 (6.5-10.5) nodes were removed per groin. A total of 153 postoperative complications (36.1%) occurred, including 50 conservatively managed wound infections (11.9%), 21 cases of deep wound dehiscence (5.0%), 104 cases of lymphoedema (24.7%), 3 cases of deep vein thrombosis (0.7%), 1 case of pulmonary embolism (0.2%), and 1 case of postoperative sepsis (0.2%). The 3-year CSS was 86% (95%Confidence Interval [95% CI] 77-96), 83% (95% CI 72-92), 58% (95% CI 51-66), respectively, for the pN1, pN2 and pN3 patients (p < 0.001), compared to a 3-year CSS of 87% (95% CI 84-95) for the pN0 patients. CONCLUSION: Fascial-sparing RILND offers excellent oncological outcomes whilst decreasing the morbidity rates. Patients with more advanced nodal involvement had poorer survival rates, emphasizing the need for adjuvant chemo-radiotherapy.

Complications and outcomes following injection of foreign material into the male external genitalia for augmentation: a single-centre experience and systematic review.

Injection of exogenous material into the penis and scrotum has been performed for augmentation purposes. Complications include cosmetic dissatisfaction, penile necrosis and lymphoedema. We report the complications and outcomes from a single centre with an updated systematic review of the literature. A retrospective review of all cases presenting with foreign substance injection into the genitalia, over a 10-year period was performed. Thirty-five patients with a mean (standard deviation (SD); range) age of 36.9 (±9.1; 22-61) years at presentation were included. The mean (SD; range) time between injection and presentation was 7.8 (±5.8; 1 day-20 years) years. The most common injected substance was silicone (n = 16, 45.7%) and liquid paraffin (n = 8, 22.9%). The penile shaft (94.3%) was the most injected site. The most common presentations were cosmetic dissatisfaction (57.1%) and pain and/or swelling (45.7%). Surgery was required in 32 (91.4%) cases. Primary procedures included local excision and primary closure (n = 19, 59.4%), circumcision (n = 5, 15.6%), excision with a split skin graft or a scrotal flap reconstruction (n = 5, 15.6%). Three (8.6%) patients presented with necrosis and required acute debridement. Overall, 18 patients had more than 1 procedure, and 8 patients required 3 or more procedures. A systematic search of the literature identified 887 articles of which 68 studies were included for analysis. The most common substance injected was paraffin (47.7%), followed by silicone (15.8%). The majority of patients (77.9%) presented with pain, swelling or penile deformity. 78.8% of the patients underwent surgical treatment, which included excision and primary closure with or without the use of skin grafts (85.1% of all procedures), the use of flaps (12.3%) and penile amputation (n = 2). Complications of foreign body injection into the male genitalia can be serious resulting in necrosis and autoamputation. Surgical intervention is often required to excise abnormal tissue to manage pain and improve cosmesis.

Treatment of Persistent or Recurrent Varicoceles: A Systematic Review.

CONTEXT: The outcomes and morbidity following treatment for persistent or varicocele recurrence remain controversial. OBJECTIVE: To conduct a systematic review relating to the outcomes following treatment (any surgical or radiological) for varicocele persistence/recurrence. EVIDENCE ACQUISITION: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Prospective and retrospective observational or interventional studies were included until March 2022. Outcomes were pregnancy rate, improvements in semen parameters after treatment compared with those at baseline, pain control, complication rates, and repeat treatment approach. Men of any age with any-grade persistent/recurrent varicoceles were included. EVIDENCE SYNTHESIS: Of 913 articles identified, 18 with 1073 patients were eligible for inclusion. The mean time between the first and repeat treatment ranged between 5.3 and 73.3 months. The indication for repeat treatment was infertility in eight and pain control in six out of 18 studies, whereas four did not provide details for the indication. Of the patients with recurrent/persistent varicoceles initially treated using a radiological intervention, 83.8% underwent another radiological procedure, whereas 16.2% underwent a surgical procedure. Of those initially treated with a surgical procedure, 77.8% underwent a further surgical procedure, whereas 22.2% underwent a radiological procedure. The rate of success of repeat treatment was 60-100%. The reported complications were as follows: hydrocele (up to 16%), testicular atrophy (up to 2%), scrotal hematoma (up to 1.6%), wound infection (up to 6.6%), chronic pain (up to 2.9%), injury to other organs (up to 10%), and thrombophlebitis (up to 5.8%). The rate of symptom resolution was >90% for pain control. Pregnancy rates were 17-58% at 12-month follow-up. Semen parameters improved after repeat treatment compared with that at baseline in 87.5% of studies. The main limitations are the high risk of bias according to the Newcastle and Ottawa Scale, heterogeneity of the included studies, and small simple size. CONCLUSIONS: Treating any grade of persistent/recurrent varicoceles has a good rate of success, pregnancy, and pain control, but there is still a risk of complications. Repeat treatment with the same interventional modality is feasible. The level of evidence is overall low. PATIENT SUMMARY: In this systematic review on persistent or recurrent varicoceles, we showed that repeat treatment with radiological or surgical procedures was feasible, with good success, pregnancy, and pain control rates at follow-up. However, repeat treatment was associated with a higher risk of complications than reported in the published literature relating to patients having their first intervention.

Diagnostic Accuracy of Dynamic Sentinel Lymph Node Biopsy for Penile Cancer: A Systematic Review and Meta-analysis.

CONTEXT: A dynamic sentinel lymph node biopsy (DSNB) is used for inguinal lymph node staging in patients presenting with primary penile cancer with clinically impalpable inguinal lymph nodes (cN0). Further completion radical inguinal lymph node dissection (RLND) is offered to patients diagnosed with metastatic inguinal nodes following a DSNB. OBJECTIVE: To identify the diagnostic accuracy of a DSNB and RLND to detect lymph node metastasis. EVIDENCE ACQUISITION: A systematic literature search was performed on PubMed Medscape, EMBASE, Google Scholar, and Cochrane database for relevant studies between January 1, 2000 and April 30, 2022. Studies were included if a DSNB was offered to cN0 patients and if RLND was offered to patients with positive histology at the DSNB. Risk of bias and confounding assessments were performed. Diagnostic odds ratio, pooled sensitivity/specificity, and heterogeneity analyses were displayed. EVIDENCE SYNTHESIS: Overall, 2893 patients in the 28 studies analysed underwent a DSNB. Twenty-one studies reported patients undergoing RLND for a positive DSNB. A DSNB showed pooled weighted sensitivity of 0.87 (95% confidence interval [CI]: 0.82-0.91) and pooled log diagnostic odds ratio of 6.17 (95% CI: 5.47-6.87). A DSNB showed pooled weighted sensitivity of 0.50 (95% CI: 0.24-0.59), specificity of 0.82 (95% CI: 0.78-0.87), and a log diagnostic odds ratio of 1.18 (95% CI: 0.29-2.97) for detecting further positive lymph nodes at RLND. High heterogeneity, mostly caused by study design, characteristics of the included patients, DSNB technique used, surgical experience/centre case volumes, and follow-up schedule, represents the main limitation of this meta-analysis. Several sensitivity analyses to address these issues support our findings. CONCLUSIONS: A positive DSNB is poorly able to discriminate which patients will have further metastatic involvement at completion RLND. Better stratification of these patients would avoid unnecessary overtreatment and possible postoperative comorbidities. PATIENT SUMMARY: This analysis of the data from the published literature provides evidence that the diagnostic accuracy of a dynamic sentinel lymph node biopsy (DSNB) requires further improvement. Moreover, a high proportion of patients with a positive DSNB undergo unnecessary radical lymph node dissection; better stratification of these patients might help determine avoidable overtreatment and postoperative comorbidities.

News and future perspectives of non-surgical treatments for erectile dysfunction.

The significant discontinuation rate of available therapies and the paucity of curative options promoted the research on potential novel treatments suitable for erectile dysfunction patients. The aim of this study was to provide a summary of available evidence regarding the news and future perspectives related to the non-surgical treatment of erectile dysfunction. A narrative review of the literature was performed. A comprehensive search in the MEDLINE, Embase, and Scopus databases was done. Papers in English-language, published until April 2022, were included. No chronological restriction was applied. Retrospective and prospective clinical studies, as well as meta-analyses, were considered. Oro-dispersible formulations of phosphodiesterase type 5 inhibitors are particularly indicated in patients who have difficulty in swallowing solid dosage form; in addition, they constitute a discrete route of administration not requiring water. Low-intensity extracorporeal shock wave therapy is indicated in mild vasculogenic erectile dysfunction and in patients with vasculogenic erectile dysfunction poorly responsive to phosphodiesterase type 5 inhibitors. Stem cell therapy, platelet-rich plasma injections, and gene therapy seem promising regenerative treatments for selected patients with erectile dysfunction. Novel oral formulations of drugs commonly used in erectile dysfunction patients have recently become part of standard clinical practice. Regenerative treatments have been emerging in recent years and could become routine curative options in the near future. Further well-designed randomized controlled trials are needed to provide conclusive evidence on this topic and guide appropriate recommendations.

The Current Role and Implications of Stem Cell Therapy in Erectile Dysfunction: A Transformation from Caterpillar to Butterfly Is Required.

Current noninvasive treatments for erectile dysfunction (ED) include oral medications, intracavernosal injections, and vacuum-assisted devices. Although these therapies work well for many, some patients experience side effects or are unsatisfied with these therapeutic modalities. Restorative therapies are the newest frontier for ED treatments and are focused on regenerating injured tissue and delivering a possible "cure". Stem cell therapy is a regenerative treatment aimed at restoring normal erectile physiology and curing ED. It is promising in cell-based and animal studies and has now been studied in humans. Although the clinical results are not robust, future research may shed more light on the efficacy of this treatment for ED. PATIENT SUMMARY: Stem cell therapy is a promising regenerative treatment for erectile dysfunction, but the clinical results are not robust. It is currently considered an experimental treatment and should not be used outside a clinical trial setting.

The Effect of Varicocele Treatment on Fertility in Adults: A Systematic Review and Meta-analysis of Published Prospective Trials.

CONTEXT: The benefits and harms of varicocele treatment versus observation in adult infertile males are still controversial. OBJECTIVE: To systematically pool the evidence on outcomes of varicocele treatment (any surgical or radiological) versus observation in adult infertile men. EVIDENCE ACQUISITION: A systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Only prospective randomized and nonrandomized studies were included until November 2021. The primary outcome was pregnancy rate; the secondary outcomes were improvements in sperm concentration, normal morphology, and progressive sperm motility after treatment compared to baseline. Men ≥18 yr of age with any-grade varicoceles were included. EVIDENCE SYNTHESIS: Of 557 articles identified, 12 were eligible for inclusion, involving 1357 patients. Varicoceles were treated surgically in ten and radiologically in four studies. Varicocele treatment improved pregnancy rates (odds ratio 1.29; 95% confidence interval [CI] 1.00-1.65; p = 0.048) and sperm concentration (mean difference 12.34 million/ml, 95% CI 3.49-21.18; p = 0.006) compared with observation. Proportions of spermatozoa with normal morphology and progressive motility were not statistically different from those with observation. However, considering treatment arm only, sperm concentration, progressive motility, and normal sperm morphology were improved compared with baseline. A subgroup analysis showed that the benefit of varicocele treatment is evident in men with an abnormal semen analysis. The main limitation is represented by the heterogeneity of the included studies, mostly in terms of study population, fertility of the partner, outcome evaluation, lack of long-term outcomes, and intermediate/high risk of bias. CONCLUSIONS: Treatment of any-grade varicoceles may improve pregnancy rates and sperm concentration in adult infertile men, while benefits in sperm motility and normal morphology are less clear. PATIENT SUMMARY: In this systematic review and meta-analysis of all published prospective trials on varicocele treatment, significant evidence emerged on its benefit in terms of improved pregnancy rates and sperm concentration, while benefits in sperm motility and morphology are less clear.

Are finasteride-related penile curvature/Peyronie's disease Adverse Event Reports worthy of further clinical investigation? Disproportionality analysis based on both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) pharmacovigilance databases.

A limited number of studies have described patients on finasteride showing findings which were consistent with Peyronie's disease (PD). We aimed to detect a pharmacovigilance signal of possible association between finasteride and PD-related clinical features. The Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database was queried to identify the ten drugs which were associated the most with the adverse drug reactions (ADRs) recorded as "penile curvature" and/or "Peyronie's disease". A similar analysis, including the same drugs, was carried out for the EMA (European Medicines Agency) EudraVigilance (EV) database. Descriptive data have been analyzed, and Proportional Reporting Ratios (PRRs) have been computed against the other nine drugs of the database. Overall, 860 reports of "penile curvature" and/or "Peyronie's disease", were identified in the FAERS database, 214 of which (24.9%) were associated with finasteride. Most reports (56.9%) were submitted by healthcare professionals. Where a treatment-indication was stated, the vast majority of reports (176/210; 83.8%) were associated with androgenetic alopecia. The outcome of most ADRs was "serious" (82.2%), with 96 ADRs resulting in levels of permanent disability. For 97/214 individual cases, penile curvature/PD reports were not part of a syndromic cluster suggestive of post-finasteride syndrome (PFS). The PRR resulted 6.6 (95% CI: 5.6-7.8) and 11.8 (95% CI: 9.08-15.33), respectively, in the FAERS and in the EV databases. Notwithstanding the related limitations and biasing factors of pharmacovigilance studies based on spontaneous reporting, the PRR values here identified should be interpreted as strong signals of disproportionality. These findings, per se, are however not useful to confirm any causal association. Clinical studies are needed to investigate on the possible role for finasteride in causing PD-related clinical features, an hypothesis which remains highly speculative due to the very questionable quality of present data.

Management of small testicular masses: outcomes from a single-centre specialist multidisciplinary team.

OBJECTIVES: To report the management outcomes of men with ≤20-mm small testicular masses (STMs) and to identify clinical and histopathological factors associated with malignancy. PATIENTS AND METHODS: A retrospective analysis of men managed at a single centre between January 2010 and December 2020 with a STM ≤20 mm in size was performed. RESULTS: Overall, 307 men with a median (interquartile range [IQR]) age of 36 (30-44) years were included. Of these, 161 (52.4%), 82 (26.7%), 62 (20.2%) and 2 men (0.7%) underwent surveillance with interval ultrasonography (USS), primary excisional testicular biopsy (TBx) or primary radical orchidectomy (RO), or were discharged, respectively. The median (IQR) surveillance duration was 6 (3-18) months. The majority of men who underwent surveillance had lesions <5 mm (59.0%) and no lesion vascularity (67.1%) on USS. Thirty-three (20.5%) men undergoing surveillance had a TBx based on changes on interval USS or patient choice; seven (21.2%) were found to be malignant. The overall rate of malignancy in the surveillance cohort was 4.3%. The majority of men who underwent primary RO had lesions ≥10 mm (85.5%) and the presence of vascularity (61.7%) on USS. Nineteen men (23.2%) who underwent primary TBx (median lesion size 6 mm) had a malignancy confirmed on biopsy and underwent RO. A total of 88 men (28.7%) underwent RO, and malignancy was confirmed in 73 (83.0%) of them. The overall malignancy rate in the whole STM cohort was 23.8%. Malignant RO specimens had significantly larger lesion sizes (median [IQR] 11 [8-15] mm, vs benign: median [IQR] 8 [5-10] mm; P = 0.04). CONCLUSIONS: Small testicular masses can be stratified and managed based on lesion size and USS features. The overall malignancy rate in men with an STM was 23.8% (4.3% in the surveillance group). Surveillance should be considered in lesions <10 mm in size, with a TBx or frozen-section examination offered prior to RO in order to preserve testicular function.

Contemporary Management of Male Anterior Urethral Strictures by Reconstructive Urology Experts-Results from an International Survey among ESGURS Members.

Assessment of anterior urethral stricture (US) management of European urology experts is relevant to evaluate the quality of care given to the patients and plan future educational interventions. We assessed the practice patterns of the management of adult male anterior US among reconstructive urology experts from European countries. A 23-question online survey was conducted among European Association of Urology Section of Genito-Urinary Reconstructive Surgeons (ESGURS) members. A total of 88 invitations were sent by email at two different times (May and October 2019). Data were prospectively collected from May 2019 to December 2019. The response rate was 55.6%. Most of the responders were between 50 and 59 y.o. and mainly from University Public Teaching/Academic Hospitals. A total of 73.5% treated ≥20 patients/year with US. Retrograde urethrogram (RUG) was the commonest diagnostic tool, followed by uroflowmetry (UF) +/− post-void residual (PVR). Urethroplasty using grafts was the most frequent treatment (91.8%). Of responders, 55.3% performed >20 urethroplasties/year. Anastomotic urethroplasties were performed by 83.7%, skin flap repairs by 61.2%, perineal urethrostomy by 77.6% and non-transecting techniques by 63.3%. UF was the most common follow-up tool. Most of the responders considered urethroplasty as the primary option when indicated. Male anterior US among ESGURS members are treated mainly using urethroplasty graft procedures. RUG is preferred for diagnosis, and UF for follow-up.

Medications mostly associated with priapism events: assessment of the 2015-2020 Food and Drug Administration (FDA) pharmacovigilance database entries.

A range of drugs have a direct role in triggering ischaemic priapism. We aimed at identifying: a) which medications are associated with most priapism-reports; and, b) within these medications, comparing their potential to elicit priapism through a disproportionality analysis. The FDA Adverse Event Reporting System (FAERS) database was queried to identify those drugs associated the most with priapism reports over the last 5 years. Only those drugs being associated with a minimum of 30 priapism reports were considered. The Proportional Reporting Ratios (PRRs), and their 95% confidence intervals were computed. Out of the whole 2015-2020 database, 1233 priapism reports were identified, 933 of which (75.7%) were associated with 11 medications with a minimum of 30 priapism-reports each. Trazodone, olanzapine and tadalafil showed levels of disproportionate reporting, with a PRR of 9.04 (CI95%: 7.73-10.58), 1.55 (CI95%: 1.27-1.89), and 1.42 (CI95%: 1.10-1.43), respectively. Most (57.5%) of the reports associated with the phosphodiesterase type 5 inhibitors (PDE5Is) were related with concomitant priapism-eliciting drugs taken at the same time and/or inappropriate intake/excessive dosage. Patients taking trazodone and/or antipsychotics need to be aware of the priapism-risk; awareness among prescribers would help in reducing priapism-related detrimental sequelae; PDE5I-intake is not responsible for priapism by itself, when appropriate medical supervision is provided.

Lymphovascular and perineural invasion are risk factors for inguinal lymph node metastases in men with T1G2 penile cancer.

PURPOSE: To analyse the risk of inguinal lymph node (ILN) metastases in T1G2 penile cancer stratified by lymphovascular invasion (LVI), perineural invasion (PNI) and tumour size. METHODS: Retrospective study of men with localised T1G2 penile cancer with non-palpable lymph nodes and no local recurrence during follow-up at six European institutional high-volume centres was performed. ILN involvement was defined as cancer detected during ultrasound-guided fine-needle aspiration cytology, core needle biopsy, dynamic sentinel lymph node biopsy, ILN dissection or inguinal recurrence during follow-up. Uni- and multivariable logistic regression analyses were performed. RESULTS: In the cohort of 554 men with T1G2 penile cancer, from 6 European institutions, ILN metastases were observed in 46/554 men (8%, 95% confidence interval (CI) 6-11%). Men with both, LVI- and PNI- primary cancers had the lowest risk of ILN involvement (6%) whereas men with LVI + or PNI + showed ILN metastases in 22% and 30%. In multivariable regression, men with LVI + or PNI + had higher odds for ILN metastases compared to men with LVI- and PNI- (OR 3.9, 95% CI 1.6-9.0, p value < 0.01) Tumour size was not associated with ILN risk (OR 1.01 95% CI 0.99-1.04, p = 0.17). CONCLUSION: Approximately, one out of ten men with T1G2 overall and one out of four men with either LVI + or PNI + still have ILN metastases despite being clinically node negative. Therefore, invasive ILN staging should strongly be recommended in T1G2 with LVI + or PNI + but importantly, must be discussed in patients with T1G2 with LVI- or PNI-.

Male genital lichen sclerosus, microincontinence and occlusion: mapping the disease across the prepuce.

BACKGROUND: Male genital lichen sclerosus (MGLSc) can lead to significant sexual dysfunction and urological morbidity, and is also a risk factor for premalignant disease (penile intraepithelial neoplasia and penile cancer), particularly squamous cell carcinoma. Although the precise aetiopathogenesis of MGLSc remains controversial, accumulated evidence indicates that it is related to chronic, intermittent, occluded exposure to urine. AIM: To perform spatial mapping of MGLSc across the human prepuce and assess how this supports the urinary occlusion hypothesis. METHODS: Preputial samples were collected from 10 patients with clinically diagnosed MGLSc undergoing circumcision. The samples were then divided into a grid pattern and 10 punch biopsies were obtained from each section to determine the extent and distribution of the disease process across each prepuce. RESULTS: All 10 patients reported having urinary microincontinence, and all were histologically confirmed as having MGLSc. The most proximal aspect of the prepuce was found to be universally affected by MGLSc in all patients, whereas the most distal part was overwhelmingly shown to be the least affected area. Of the 63 MGLSc-affected regions, 62 were in direct physical contiguity with one another. The histological extent of the disease was not found to be congruent with either the severity of the symptoms reported by the patients or the clinical examination. CONCLUSION: In uncircumcised men with urinary microincontinence, after the prepuce has been replaced post micturition, small amounts of urine can pool between the juxtaposed epithelial surfaces. The proximal aspect of the prepuce is subjected to the maximum amount of occlusion and maximal contact with accumulated urine, whereas the distal prepuce is subjected to the least. Our findings suggest that accentuated contact between urine and susceptible penile epithelium due to occlusion can lead to MGLSc. Furthermore, contiguity data suggest that once established, it is possible that MGLSc advances across tissues by physical contact. This is the first study examining the changes in the preputial landscape in patients with LSc and contributes to our understanding of disease aetiology and progression.