Endocrine outcome and seminal parameters in young adult men born with hypospadias: A cross-sectional cohort study.

BACKGROUND: Hypospadias affects around 1/200 newborn males. Intrauterine testicular dysfunction may underlie a subset of cases. The long-term endocrine and reproductive outcomes in these men remain largely unknown. METHODS: Cross-sectional study in Ghent and Vienna University Hospitals to assess the endocrine and seminal parameters of young adult men (16-21 years) born with non-syndromic hypospadias (NSH) (n = 193) compared to healthy typical males (n = 50). Assessments included physical exam, semen analysis, hormone assays and exome-based gene panel analysis (474 genes). FINDINGS: All participants had experienced a spontaneous puberty, in spite of higher LH and INSL3 levels than typical males. Oligo- or azoospermia was observed in 32/172 (18·6%; 99%-CI: 12·2-27·4%) of NSH men; but in 5/16 (31·3%; 99%-CI: 11·1;62·4%) of complex NSH men and in 13/22 (59·1%; 99%-CI: 33·2-80·7%) of those born small for gestational age (SGA). No (likely) pathogenic coding variants were found in the investigated genes. Suboptimal statural growth affected 8/23 (34·8%; 99%-CI: 15·4-61·0%) of men born SGA with NSH. INTERPRETATION: Spermatogenesis is significantly compromised in NSH men, especially in those born SGA or those with complex NSH. Long-term andrological follow-up is recommended, including end-pubertal semen analysis. No clear monogenic causes could be demonstrated in our cohort even in proximal or complex NSH. Being born SGA with NSH is frequently associated with poor catch-up growth, requiring growth hormone therapy in some. FUNDING: Research grants from the European Society of Paediatric Endocrinology, the Belgian Society of Pediatrics, the Belgian Society of Pediatric Endocrinology and Diabetology and the Research Foundation Flanders (FWO).

Guideline Adherence of Paediatric Urolithiasis: An EAU Members' Survey and Expert Panel Roundtable Discussion.

Background: Paediatric nephrolithiasis has increased globally, requiring standardized recommendations. This study aims to assess the paediatric urolithiasis care between EAU members along with the statements of three experts in this field. Methods: The results of an electronic survey among EAU members comparing the guideline recommendations to their current practice managing paediatric nephrolithiasis in 74 centres are contrasted with insights from an expert-panel. The survey consisted of 20 questions in four main sections: demographics, instrument availability, surgical preferences and follow-up preferences. Experts were asked to give insights on the same topics. Results: A total of 74 responses were received. Computerised Tomography was predominantly used as the main imaging modality over ultrasound. Lack of gonadal protection during operations was identified as an issue. Adult instruments were used frequently instead of paediatric instruments. Stone and metabolic analysis were performed by 83% and 63% of the respondents respectively. Conclusions: Percutaneous Nephrolithotomy is the recommended standard treatment for stones > 20 mm, 12% of respondents were still performing shockwave lithotripsy despite PNL, mini and micro-PNL being available. Children have a high risk for recurrence yet stone and metabolic analysis was not performed in all patients. Expert recommendations may guide clinicians towards best practice.

Adolescent and Young Adult Urogenital Outcome following Childhood Hypospadias Repair: Perfection Revisited.

PURPOSE: We assessed the long-term surgical, functional urinary and sexual outcomes of adolescent and young adult men who underwent childhood hypospadias repair. MATERIALS AND METHODS: Men born with nonsyndromic hypospadias and healthy male controls aged 16-21 years old were recruited, and their surgical, urinary, sexual functional and aesthetic outcomes assessed. Good outcome was defined as a patent and orthotopic meatus without fistulas, and straight erections (<30 degree curvature) without erectile or ejaculatory problems. Statistics included regression analyses, chi-square/Fisher exact tests and Student's t/Mann-Whitney U and Kruskal-Wallis tests. RESULTS: A total of 193 patients and 50 controls participated 16.4 years (range 8.2-21.2) after initial repair. At least 1 reintervention was performed in 39.2%. The highest reintervention rate was found in those younger than 12 months at initial repair, even when excluding proximal hypospadias cases. A disturbed urinary and/or suboptimal sexual functional outcome was seen in 52.9% of cases. Suboptimal voiding was found in 22.1%, although few had relevant residual urine. More reinterventions and proximal hypospadias cases were associated with suboptimal urinary outcome, and the latter also with impaired sexual function. Poor inter-observer agreements were found between physician and patient genital appraisal. CONCLUSIONS: In 52.9% of cases, at least 1 concern was identified that required long-term followup. Hypospadias repair below 12 months was associated with more reinterventions. Adopting a restrictive attitude toward aesthetic refinement, unless on the patient's own request, could improve urinary outcomes.

αßγδ T cells play a vital role in fetal human skin development and immunity.

T cells in human skin play an important role in the immune defense against pathogens and tumors. T cells are present already in fetal skin, where little is known about their cellular phenotype and biological function. Using single-cell analyses, we identified a naive T cell population expressing αß and γδ T cell receptors (TCRs) that was enriched in fetal skin and intestine but not detected in other fetal organs and peripheral blood. TCR sequencing data revealed that double-positive (DP) αßγδ T cells displayed little overlap of CDR3 sequences with single-positive αß T cells. Gene signatures, cytokine profiles and in silico receptor-ligand interaction studies indicate their contribution to early skin development. DP αßγδ T cells were phosphoantigen responsive, suggesting their participation in the protection of the fetus against pathogens in intrauterine infections. Together, our analyses unveil a unique cutaneous T cell type within the native skin microenvironment and point to fundamental differences in the immune surveillance between fetal and adult human skin.

The microbiome in urinary tract infections in children - an update.

PURPOSE OF REVIEW: Urinary tract infection (UTI) is one of the most common pediatric infections worldwide. Recently introduced 16S rRNA sequencing allows detailed identification of bacteria involved in UTI on a species-based level. The urogenital microbiome in children is scarcely investigated, with underlying conditions differing from adults. Improvement in diagnostic and therapeutic approaches can help to minimize unnecessary antibiotic treatments, thereby protecting the physiological microbiome. RECENT FINDINGS: Healthy bladders of children display a distinct microbiome than those of adults. UTI is characterized by changes in bacterial composition, with a high prevalence of Enterobacterales. There is a correlation between bacterial species and the pH of the urine, so a characteristic age-related pathogen pattern can be found due to the acidic urine in infants and more alkaline urine in older children. Recently, new methods were proposed to overcome the suboptimal diagnostic performance of urine cultures and urine dipstick test. This allows precise treatment decisions and helps to prevent chronification of UTI, related voiding dysfunctions and renal scaring, systemic abiosis, and the development of antibiotic resistance. SUMMARY: Uropathogens involved in UTIs in children should be identified with precision to allow targeted therapeutic decisions. This can also help preventing the destruction of the microbiome homeostasis, which could result in a life-long dysbiosis. New treatment approaches and recolonization with probiotics are necessary due to increasing intrinsic antibiotic resistance of bacteria.

Medical approach to children who may have been sexually abused-a narrative review.

The medical approach to children who may have been sexually abused involves several issues and aspects that need to be considered. The medical examination of children with suspected sexual abuse is important, but a detailed medical history from the child and the parents or caretakers is always part of every thorough examination. It can take a long time until victims disclose their abuse and physical signs of abuse may no longer be visible at the time of examination. If the physical examination is performed non-acutely, only 2.2% of sexually abused girls show diagnostic signs of injury. An experienced examiner should ideally perform the examination in suspected sexual abuse of children. Knowledge of the current literature is of importance, as the interpretation of findings has changed over the past decades and it can be difficult to differentiate between normal variants, symptoms of other medical problems, and signs of sexual assault. Furthermore, sexual abuse of children presents in various form, not necessarily leading to physical injuries. Since 1992, Adams et al. publish a regularly updated system for the classification of anogenital findings in children with suspected sexual abuse, including a detailed list of physical findings and infections related to sexual abuse. The purpose of this article is to summarize important aspects of the medical approach to children with suspected sexual abuse according to the current literature.

Sexual function in adult patients who have undergone augmentation surgery in childhood: what is really important?

Problems relating to the development of a healthy approach to sex and intimacy during puberty, after augmentation cystoplasty, are scarcely discussed in literature. Therefore, this may suggest that such issues are insufficiently addressed by pediatric urologists. We gathered four experts in the field as well as an experienced leader of a patient group and mother of a girl with spina bifida and asked questions relevant to the following areas of care: (a) diversion, urinary incontinence, and sexual life; (b) impact of a stoma on body image perception and self-esteem; (c) specific female concerns with regard to fertility and recurrent urinary infections; (d) specific male concerns on anejaculation and erectile dysfunction. Their answers are discussed in view of the available literature. All experts and the patient group representative agreed that most of these patients will experience: lack of self-confidence as the most frequent obstacle to starting a relationship and incontinence as a barrier to sexual activity. The cosmesis of the stoma and abdominal scars might influence self-esteem and therefore the sexual activity, however it appears to be a less common concern in males than females. Our results outline the importance and influence that the body image, self-esteem, and confidence present for the individual expectations of the patients related to sex life and sexual activity. Physicians should be encouraged to ask all postpubertal patients about their sexual concerns at every visit. Further studies and exchange of information between clinicians are needed to provide meaningful and analyzable patient-related outcome measures (PROMs).

The Whey Acidic Protein WFDC12 Is Specifically Expressed in Terminally Differentiated Keratinocytes and Regulates Epidermal Serine Protease Activity.

WFDC proteins such as peptidase inhibitor 3 and SLPI inhibit proteases in the epidermis and other tissues. In this study, we tested the hypothesis that further WFDC protein family members might contribute to epidermal homeostasis. We found that in addition to peptidase inhibitor 3 and SLPI, WFDC5 and WFDC12 were expressed in human epidermis. In contrast to WFDC5, the expression of WFDC12 was induced during the late differentiation of keratinocytes and was restricted to the outermost layer of live cells. Single-cell RNA sequencing demonstrated that WFDC12-positive keratinocytes were characterized by the upregulation of LCE mRNA expression and downregulated the expression of keratins and claudins. Immunogold-electron microscopy revealed the colocalization of WFDC12 with corneodesmosomes in the lower stratum corneum. WFDC12 was elevated in the affected skin of patients with psoriasis, atopic dermatitis, and Darier disease. By contrast, WFDC12 expression was strongly upregulated not only in the affected but even more so in clinically normal-appearing skin of patients with Netherton syndrome. Finally, functional analysis showed distinct inhibitory activity of WFDC12 on neutrophil elastase and epidermal kallikrein‒related peptidase. Altogether, our study identified WFDC12 as a marker of the last stage of epidermal keratinocyte differentiation and suggests that WFDC12 contributes to the control of protease activity in the stratum corneum.

Psychosexual Outcome, Sexual Function, and Long-Term Satisfaction of Adolescent and Young Adult Men After Childhood Hypospadias Repair.

BACKGROUND: The psychosexual outcome in adolescents and young adults (AYA) men born with hypospadias is precarious. However, the factors responsible for impaired outcome in some AYA men have been understudied. AIM: To explore the outcome after hypospadias repair in childhood of AYA men aged 16-21 years and examine their opinion and their parents' opinion about this type of surgery. METHODS: Cross-sectional assessment of 193 AYA men born with hypospadias and 50 male controls was performed. Questionnaires such as the Decision Regret Scale, Pediatric Penile Perception Score, Sexual Quality of Life-Male, International Index of Erectile Function, and a custom-made questionnaire were used. The Decision Regret Scale and a custom-made questionnaire were also completed by the participants' parents. Physical examination including Hypospadias Objective Penile Evaluation and measuring stretched penile length was performed. OUTCOMES: This study reports the psychosexual functioning (ie, social, relational, and sexual), erectile and sexual function after childhood hypospadias repair, using ad hoc measures. In addition, the opinion about hypospadias repair of patients and their parents is represented. RESULTS: The number of surgeries and satisfaction regarding penile appearance were the most important factors associated with the opinion on hypospadias repair and the psychosexual outcome. Most AYA men were more satisfied with their penile appearance than the physician. 80% of men were satisfied with having had a childhood hypospadias repair, even though they had not been able to consent to surgery themselves. Erectile and ejaculation problems were mild and seen in approximately 10% of the population. CLINICAL IMPLICATIONS: Based on our data, deferring hypospadias repair until the patient can decide himself is not warranted. However, physicians who accept a suboptimal esthetic outcome and withdraw from repeated surgery may contribute importantly to the patient's well-being, especially in proximal forms of hypospadias. STRENGTHS & LIMITATIONS: This is one of the rare studies addressing the AYA's psychosexual outcome after childhood hypospadias repair. Strengths include the combination of clinical and psychosexual data from a very large cohort of men and their parents to provide a more holistic view. By entering this study, participants might have a different comfort level regarding their sexuality or have a different body image than the overall population of young men. CONCLUSION: Uncomplicated hypospadias surgery results in equal psychosexual outcome as controls and in high satisfaction rates; multiple surgeries are a risk factor for poorer outcomes. 80% of men are satisfied with childhood hypospadias repair. Tack LJW, Springer A, Riedl S, et al. Psychosexual Outcome, Sexual Function, and Long-Term Satisfaction of Adolescent and Young Adult Men After Childhood Hypospadias Repair. J Sex Med 2020;17:1665-1675.

Midline Incision of a Graft in Staged Hypospadias Repair-Feasible and Durable?

Purpose: In severe hypospadias staged repair is commonly used and it is regarded as feasible, safe, and durable. In this article we want to describe the results of a modification of the staged repair: a midline incision of the graft during the second stage. Materials and Methods: This is a consecutive single team (2 surgeons) retrospective series. Between 2014 and 2017, 250 patients underwent hypospadias repair, among them 35 patients that had primary staged hypospadias surgery with completed first and second stage repair. 24 (68.6%) cases received a preputial skin graft and 11 (31.4%) buccal mucosa graft. Median age at first stage was 1.5 (0.5-22.1) years, mean time between first and second stage operation was 0.72 (0.4-1.76) years. Follow up rate was 100%, mean follow up period was 1.50 (0.4-3.8) years. Results: The total complication rate was 22.9%. In buccal mucosa repair the complication rate was 36.4% and in preputial graft repair the complication rate was 16.7%, respectively. In 23 patients (65.7%) during second stage urethroplasty a midline incision was performed (8 glandular graft, 15 penile graft, 6 at level of urethral opening). Complication rate in non-incised urethroplasty was 8.3%, in incision at glandular level 37.5%, in incision at penile level 13.3% and in incision at urethral opening 16.7%, respectively. Conclusions: Two stage repair is the method of choice in the correction of severe hypospadias. In selected cases a midline incision of the graft is feasible and can be applied if needed. Randomized studies will be needed to evaluate the true benefit of incising the graft.

Validation of lymphovascular invasion is an independent prognostic factor for biochemical recurrence after radical prostatectomy.

OBJECTIVE: To validate the impact of lymphovascular invasion (LVI) on biochemical recurrence (BCR) in patients treated with radical prostatectomy (RP) in a large multiinstitutional cohort. MATERIAL AND METHODS: Retrospective data from 6,678 patients treated with a RP and bilateral lymphadenectomy for prostate cancer (PC) from 8 centers were collected. The primary endpoint was BCR. RESULTS: Overall, 767 patients (11.5%) had LVI. Patients with LVI had significantly higher Gleason scores (P = 0.01). After a median follow-up of 28 months (interquartile range: 21-44), patients with LVI had a 1.66 fold increased risk of BCR (P<0.001). The 1-, 2- and 5-year biochemical recurrence-free survival probabilities for LVI vs. no LVI were 94% vs. 97%, 91% vs. 94%, and 76% vs. 84%, respectively. On multivariable analysis that adjusted for the effects of established prognostic factors, LVI was an independent predictor of BCR (hazard ratio = 1.42, P<0.001). Adding LVI to a multivariable base model increased the discrimination by a small but significant margin (+0.2%, P = 0.0005). In subgroup analyses, LVI remained an independent predictor for BCR in patients with worse pathological features. CONCLUSIONS: About 10% of patients with localized PC have LVI on their RP specimen. We confirm that LVI is associated with features of biologic aggressive PC such as high Gleason grade and BCR after RP. Adverse further studies with strict definitions of LVI and longer follow-up periods are needed to determine the prognostic and predictive utility of LVI in the management of PC.

Robot-assisted renal surgery: current status and future directions.

This paper examines the current role of robot-assisted renal surgery as complex and partial nephrectomies, including vena cava thrombus, combined nephroureterectomies, living donor nephrectomy, autotransplantation, and difficult anatomy as in patients with obesity or adhesions. Indications for robot-assisted renal surgery are comparable to those of conventional laparoscopic approaches. A reduction in the learning curve leads to a stabilization of the procedure and further increases the number of minimally invasive procedures performed. A Medline literature search for publications on the field of robotic kidney surgery has been performed using the MeSH terms: robotic surgical procedures and kidney. Future directions include progress in robotic technology and instrumentation with further miniaturization of robotic procedures as laparoendoscopic single-site interventions and progress in image-guided robotic surgery.

Quantitative apparent diffusion coefficient measurements obtained by 3-Tesla MRI are correlated with biomarkers of bladder cancer proliferative activity.

PURPOSE: To investigate the association between Apparent Diffusion Coefficient (ADC) values and cell cycle and proliferative biomarkers (p53, p21, Ki67,) in order to establish its potential role as a noninvasive biomarker for prediction of cell cycle, proliferative activity and biological aggressiveness in bladder cancer. MATERIALS AND METHODS: Patients with bladder cancer who underwent 3,0 Tesla DW-MRI of the bladder before TUR-B or radical cystectomy were eligible for this prospective IRB-approved study. Histological specimen were immunohistochemically stained for the following markers: p53, p21 and ki67. Two board-certified uropathologists reviewed the specimens blinded to DW-MRI results. Histological grade and T-stage were classified according to the WHO 2004 and the 2009 TNM classification, respectively. Nonparametric univariate and multivariate statistics including correlation, logistic regression and ROC analysis were applied. RESULTS: Muscle invasive bladder cancer was histologically confirmed in 10 out of 41 patients. All examined tissue biomarkers were significantly correlated with ADC values (p<0.05, respectively). Based on multivariate analysis, p53 and ADC are both independent prognostic factors for muscle invasiveness of bladder cancer (>/ = T2). (p = 0.013 and p = 0.018). CONCLUSION: ADC values are associated with cell cycle and proliferative biomarkers and do thereby reflect invasive and proliferative potential in bladder cancer. ADC and p53 are both independent prognostic factors for muscle invasiveness in bladder cancer.

[The Clavien-Dindo classification of complications used for radical prostatectomy]. / Die Komplikationsklassifikation nach Clavien-Dindo am Beispiel der radikalen Prostatektomie.

The objective of the present study was to evaluate perioperative complications between retropubic, endoscopic and robot-assisted radical prostatectomy on basis of a prospective maintained database using the Clavien-Dindo classification of complications. According to our results, implementation of the radical robot-assisted laparoscopic prostatectomy shows a trend to a decrease of minor complications compared to retropubic and endoscopic radical prostatectomy. Major complications are comparable between all three procedures.

Sentinel lymphadenectomy compared to extended lymphadenectomy in men with prostate cancer undergoing prostatectomy.

BACKGROUND: To evaluate the reliability of sentinel lymphadenectomy compared to extended lymphadenectomy in men undergoing radical prostatectomy (RP). PATIENTS AND METHODS: A consecutive cohort of men with intermediate- to high-risk prostate cancer underwent RP with sentinel LA with intraoperative frozen section. In addition, extended LA was carried out in all cases. The endpoint was lymph node-positivity. RESULTS: In total, 54 men with a mean age of 65.3 (50.9-75.6) years were analyzed. The mean preoperative prostate-specific antigen was 10.6 (2.8-66.5) ng/ml, mean number of disease-positive cores was 5.8 (1-13), digital rectal examination was positive in 29 men (53.7%). In 12 men (22.2%), a positive lymph node was found (pN1). sLA was positive in 11 cases. One patient had a positive lymph node in eLA not found with sLA. The positive predictive value of frozen section was 50%; the respective figure for sLA compared to eLA was 91.6%. CONCLUSION: In this cohort, revealing a high prevalence of disease-positive lymph nodes, sLA was a reliable technique with a low rate of false negativity.