Langerhans cells in hypospadias : an analysis of Langerin (CD207) and HLA-DR on epidermal sheets and full thickness skin sections

Background: Hypospadias are among the most common genital malformations. Langerhans Cells (LCs) play a pivotal role in HIV and HPV infection. The migration of LC precursors to skin coincides with the embryonic period of hypospadias development and genetic alterations leading to the formation of hypospadias impact the development of ectodermally derived tissues. We hypothesized that this might be associated with a difference in frequency or morphology of epidermal and dermal LCs in hypospadias patients. Methods: A total of 43 patients from two centers were prospectively included into this study after parental consent and ethics approval. Epidermal and dermal sheets were prepared from skin samples of 26 patients with hypospadias, 13 patients without penile malformations and 4 patients with penile malformations other than hypospadias. Immunofluorescence staining of sheets was performed with anti-HLA-DR-FITC and anti-CD207/Langerin-A594 antibodies. Skin sections from 11 patients without penile malformation and 11 patients with hypospadias were stained for Langerin. Frequencies as well as morphology and distribution of epidermal and dermal LCs on sheets and sections were microscopically evaluated. Cell counts were compared by unpaired t-tests. Results: There was no difference in frequency of epidermal LCs, Neither on sheets (87361 vs. 940 +/- 84LCs/mm(2), p=0.522) nor on sections (32 +/- 3 vs. 30 +/- 2LCs/mm(2), p=0.697). Likewise, the frequency of dermal LCs (5,9 +/- 0,9 vs. 7.5 +/- 1.3LCs/mm(2), p=0.329) was comparable between patients with hypospadias and without penile malformation. No differences became apparent in subgroup analyses, comparing distal to proximal hypospadias (p=0.949), younger and older boys (p=0.818) or considering topical dihydrotestosterone treatment prior to surgery (p=0.08). The morphology of the LCs was not different comparing hypospadias patients with boys without penile malformations. Conclusions: p id=Par Cs are present in similar frequencies and with a comparable morphology and distribution in patients with hypospadias as compared to children without penile malformations. This suggests that patients with hypospadias are not different from patients with normal penile development considering this particular compartment of their skin immunity

Testicular-sparing surgery in the pediatric population: Multicenter review of practice with review of the literature

Purpose of review Pediatric testicular tumors have predominantly favorable histology, which may permit testicular sparing surgery (TSS). Limited guidance exists for TSS in adults and is absent in pediatric practice. The international survey and retrospective case series evaluated the current use of TSS in pediatric testicular tumors. Alongside the complementary literature review, the aim of this work was to provide evidence that could be used to produce a guideline document. Recent findings Published evidence advocates small mass size as an indicator for TSS, this was not supported in the pediatric literature. Frozen section examination at TSS was not always performed by surgeons and yet the literature reports close to 100% specificity. Tumor markers and ultrasound findings are also used as indicators for TSS, a finding reflected in our survey results. Summary Multiple case series are reported but no large data series exists, which will require international collaboration rather than a drive to publish the results of individual centers. Common indicators for TSS use; such as tumor markers and imaging are known but further work needs to evaluate the role of on-table histology and the risks of this not being available

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)

Epidermal Langerhans Cells Rapidly Capture and Present Antigens from C-Type Lectin-Targeting Antibodies Deposited in the Dermis

Antigen-presenting cells can capture antigens that are deposited in the skin, including vaccines given subcutaneously. These include different dendritic cells (DCs) such as epidermal Langerhans cells (LCs), dermal DCs, and dermal langerin+ DCs. To evaluate access of dermal antigens to skin DCs, we used mAb to two C-type lectin endocytic receptors, DEC-205/CD205 and langerin/CD207. When applied to murine and human skin explant cultures, these mAbs were efficiently taken up by epidermal LCs. In addition, anti-DEC-205 targeted langerin+ CD103+ and langerin− CD103− mouse dermal DCs. Unexpectedly, intradermal injection of either mAb, but not isotype control, resulted in strong and rapid labeling of LCs in situ, implying that large molecules can diffuse through the basement membrane into the epidermis. Epidermal LCs targeted in vivo by ovalbumin-coupled anti-DEC-205 potently presented antigen to CD4+ and CD8+ T cells in vitro. However, to our surprise, LCs targeted through langerin were unable to trigger T-cell proliferation. Thus, epidermal LCs have a major function in uptake of lectin-binding antibodies under standard vaccination conditions

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

A multi-institutional European comparative study of open versus robotic-assisted laparoscopic ureteral reimplantation in children with high grade (IV–V) vesicoureteral reflux

Introduction: Traditionally, open ureteral reimplantation (OUR) has been the standard treatment for primary vesicoureteral reflux (VUR) requiring reimplantation. Robotic-assisted laparoscopic ureteral reimplantation (RALUR) is gaining popularity and high success rates have been reported. Objective: In this multi-institutional study, we aimed to compare the perioperative and postoperative outcomes of OUR and RALUR for high-grade (IV + V) VUR in children. Study design: A retrospective evaluation was performed collecting data from 135 children (0–18 years) who underwent high grade VUR surgical correction at nine European institutions between 01/01/2009 and 01/12/2020, involving either open or robotic approaches. Institutional review board approval was obtained. Patients with lower grades of VUR (≤III), previous history of open or endoscopic ureteral surgery, neurogenic bladder, or refluxing megaureter in need of ureteral tapering were excluded. Pre-, peri- and post-operative data were statistically compared. Results: Overall, 135 children who underwent either OUR (n = 68), or RALUR (n = 67) were included, and their clinic and demographic features were collected. The mean age of the open group was 11 months (interquartile range [IQR] 9.9–16.6 months), in the RALUR group it was 59 months (IQR 29–78mo) (p &lt; 0.01); the open cohort had a weight of 11 kg (IQR 9.9–16.6 kg) while the RALUR group had 19 kg (IQR 13–25 kg) (p &lt; 0.01). No significant differences were found for intraoperative (1.5 % vs 7.5 %, p = 0.09) or for postoperative complication rates (7.4 % vs 9 %, p = 0.15). Favorable outcomes were reported in the RALUR group: shorter time to stooling (1 vs 2 days), fewer indwelling urethral catheter days (1 vs 5 days), perioperative drain insertion time (1 vs 5 days) and a shorter length of hospital stay (2 vs 5 days) (p &lt; 0.01). The success rate was 94.0 % and 98.5 % in the open and RALUR groups, respectively. The long-term clinical success rates from both groups was comparable:42 vs 23 months for open and RALUR, respectively. Discussion: This study reported a large multicentric experience focusing on high grade VUR. Furthermore, this study compares favorably to OUR in a safety analysis. There was also a trend towards higher success rates with RALUR utilizing an extravesical approach which has not been previously reported. Conclusion: RALUR is an efficacious and safe platform to use during ureteral reimplantation for high grade VUR. The overall peri-operative and post-operative complication rates are at least equivalent to OUR, but it is associated with a faster functional recovery and time to discharge. Medium to long term success rates are also equivalent to OUR.</p