ESPU Meeting on Thursday 20, April 2023, 08:20 - 09:10
08:20 - 08:23
S08-1 (OP)
Nicolas KALFA 1, Anne BERGOUGNOUX 2, Pascal PHILIBERT 3, Nadege SERVANT-FAUCONNET 2, Alice FAURE 4, Jean BREAUD 5, Laura GASPARI 1, Charles SULTAN 1 and Francoise PARIS 1
1) CHU Montpellier, Centre de Référence Maladies Rares du Développement Génital DEVGEN, Montpellier, FRANCE - 2) CHU MONTPELLIER, Laboratoire de Génétique Moléculaire, PhyMedExp, INSERM, CNRS UMR, Montpellier, FRANCE - 3) CHU Nimes, Laboratoire Biochimie, Nimes, FRANCE - 4) AP- Hôpitaux Marseille, Service de Chirurgie et Urologie Pédiatrique, Marseille, FRANCE - 5) CHU NICE, Service de Chirurgie et Urologie Pédiatrique, Nice, FRANCE
PURPOSE
The etiology of hypospadias may be at the crossroad of genetics and environment. Though the individual study of these factors failed to find an unequivocal explanation, their interactions have not yet been studied. We aimed to find a genetic susceptibility to the environment in hypospadias.
MATERIAL AND METHODS
Multicenter prospective comparative study of 300 hypospadias and 300 controls evaluated by: 1-Questionnaire QLK4-1999-01422 to detect personal, environmental, professional exposures to pollutants. 2-Next-generation-sequencing of 336 genes implicated in genital and gonadal development and hypospadias. The interaction between genetics and environment was studied using logistic regression analysis.
RESULTS
Surprisingly, genes identified as potential interactors with environment were not only genes of steroidogenesis or chemical-sensor but also oncogenes: BRAF (rs3789806), AKR1C3 (rs10508293), AHR (rs2074113) and CITED2 (rs4076025). The in-silico predictions of these variants are to modify the transcription factor binding sites for proteins encoded by other oncogenes and genital development genes. We thus hypothesized a connection between hypospadias and cancers. To further evaluate this association, we used data from the International Birth-Defect Surveillance Systems and from the International Agency for Research on Cancer (WHO). We found a spatial correlation, across 17 countries, between incidence of hypospadias and overall incidence of cancers, especially urological tumors and leukemias, two cancers highly suspected to be linked to pollutants.
CONCLUSIONS
Hypospadias is at the crossroad of genetics and environment and is associated with oncogene variants. Its incidence is spatially correlated to that of cancers worldwide. Hypospadias may not be a simple defect of the urethra but a witness of the global health population.
08:23 - 08:26
S08-2 (OP)
Lottie PHILLIPS 1, Cecilia LUNDHOLM 2, Ulrik KVIST 3, Catarina ALMQVIST 2, Agneta NORDENSKJÖLD 1 and Anna SKARIN NORDENVALL 2
1) Karolinska Institutet, Women's and Children's Health, Solna, SWEDEN - 2) Karolinska Institutet, Medical Epidemiology and Biostatistics, Stockholm, SWEDEN - 3) Karolinska Institutet, Medicine, Huddinge, Stockholm, SWEDEN
PURPOSE
Androgen function in utero is important in the etiology of hypospadias. Continued decreased androgen effect past birth can lead to clinical hypogonadism and metabolic disease as well as potentially increase the risk of cardiovascular disease. These long-term outcomes have not been previously studied in hypospadias. We therefore aimed to study the association between hypospadias and androgen-related comorbidity.
MATERIAL AND METHODS
We used national Swedish register data to study a population-based cohort of adolescents and men born 1954-2003 with hypospadias. Outcomes were defined using diagnoses codes and associations were measured using cox proportional hazards regression analysis. We also used data from military conscription to study potential differences in height, weight, and blood pressure.
RESULTS
In total, 2,165,255 men, including 9,714 with hypospadias, were included in the study population and followed from age 10. Hypospadias was associated with an increased risk of hypogonadism (Hazard ratio (HR) 3.27, 95% confidence interval (CI) 2.33–4.59), with a stronger association for proximal hypospadias. We also found associations with delayed puberty (HR1.49, 95% CI 1.08–2.07), diabetes mellitus type 2 (HR1.57, 95% CI 1.18–2.09) and cardiovascular disease (HR 1.47, 95% CI 1.27–1.71). Men with hypospadias were somewhat shorter than the general male population but had similar body mass index and blood pressure.
CONCLUSIONS
Hypospadias is associated with an increased risk of hypogonadism, delayed puberty, diabetes and cardiovascular disease. We suggest that the risk of androgen-related disease be considered clinically, especially for proximal hypospadias, while further research is needed to more fully understand cardiometabolic comorbidity.
08:26 - 08:29
S08-3 (OP)
Yu DING, Zuquan CHEN, Yi WANG, Yaping WANG, Wenfeng PAN, Kexin GAO, Fang CHEN and Zhongzhong CHEN
Shanghai Children's Hospital，School of Medicine，Shanghai Jiao Tong University, Department of Urology, Shanghai, CHINA
PURPOSE
Hypospadias is one of the most frequent male congenital reproductive development defects, and thought to be caused by abnormal testosterone levels during pregnancy. The second to the fourth digit ratio (2D:4D) is thought to be associated with prenatal androgen exposure. However, the relationship between 2D:4D ratio and hypospadias is poorly understood, and its molecular mechanism is not clear.
MATERIAL AND METHODS
142 patients with hypospadias (23 distal, 68 middle, and 51 proximal) and 196 control groups were enrolled from June 2020 to January 2022. Hand digit length was measured by the vernier caliper behind the copy. Furthermore, 2D:4D ratio was assessed and compared in low testosterone mice model and control mice. The gene and protein expression of androgen receptor (AR), estrogen receptor α (ER-α), Wnt5a and Wnt5b in 2D and 4D of foetal mice were measured.
RESULTS
The 2D:4D ratio was significantly increased in hypospadias compared to control (p<0.001), especially in proximal hypospadias. Furthermore, the discrepancy was mainly caused by a shift in 4D. The higher ratio of 2D:4D was confirmed in low testosterone mice model compared to controls (p<0.01). In addition, the expression of AR was significantly decreased (p<0.05), whereas the expression of Wnt5a was significantly increased in mice model with low testosterone level (p<0.05), resulting in a decrease of 4D proliferation and a larger 2D:4D ratio.
CONCLUSIONS
The ratio of 2D:4D is associated with the risk of hypospadias. Low testosterone levels may limit the growth of 4D during the androgen-sensitive window of urethral development via disrupting the expression of AR and Wnt, which result in a higher 2D:4D ratio. This study indicates that the ratio of 2D:4D is a risk marker of hypospadias and provides the potential molecular mechanism.
08:40 - 08:43
S08-4 (OP)
Sriman Bidhan BARAY 1, Mohamed ABDELMONIEM 2, Muhammad CHOWDHURY 2 and Tariq Osman ABBAS 3
1) University of Dhaka, Department of Electrical and Electronic Engineering, Dhaka, BANGLADESH - 2) Qatar University, Department of Electrical Engineering, Doha, QATAR - 3) Sidra Medicine, Urology, Doha, QATAR
PURPOSE
To design and verify an artificial intelligence (AI)-based algorithm for the automatic acquisition of Penile curvature (PC) measures from 2-dimensional pictures.
MATERIAL AND METHODS
A dataset of 913 2D photos of nine 3D-printed penile models (varying from 18° to 88°) at varied configurations was utilized. Using a YOLOv5 model, the penile region was initially localized and cropped. To extract the penile shaft from the cropped photos, an Unet-based model was employed. The penile shaft is then divided into three distinct regions: the distal shaft zone, the curvature zone, and the proximal shaft zone. To measure the PC, we have identified four distinct spots on the shaft, reflecting the mid axis of the proximal and distal segments of the penile shaft and all masks have been marked accordingly. Then, HRNet models were trained and verified to predict the critical spots separately
RESULTS
The proposed framework displayed robust performance in cropping the penile area [mean average precision (mAP) 99.7%] and segmenting the shaft [Dice Similarity Coefficient (DSC) 98.6%]. We got a mean absolute error (MAE) of approximately 4,273 and 4,184 for penile model pictures and their masks, respectively.
CONCLUSIONS
Considering the current intra- and inter-surgeon variability of PC evaluations, the approach presented here could greatly increase the precision of PC measurements by surgeons and hypospadiology researchers. Moreover, this approach could overcome the limitations currently encountered by all other tools when measuring arch type PC.
08:43 - 08:46
S08-5 (OP)
Mohamed ABDUL MONIEM 1, Carlos VILLANUEVA 2, Abderrahman ELKADHI 3, Muthana AL-SALIHI 3, Muhammad CHOWDHURY 1, Jl Pippi SALLE 3 and Tariq Osman ABBAS 3
1) Qatar University, Department of Electrical Engineering, Doha, QATAR - 2) Phoenix Children's Hospital/University of Arizona, Urology, Phoenix, USA - 3) Sidra Medicine, Urology, Doha, QATAR
PURPOSE
To study the feasibility and validity of an artificial intelligence (AI)-based model for the automatic measurement of penile curvature (PC).
MATERIAL AND METHODS
Seven 3D-printed penile models with varying degrees of ventral PC were used to evaluate the inter-observer agreement in PC estimation using various curvature measurement techniques, including visual inspection, goniometer, manual estimation via a mobile application, and an artificial intelligence (AI)-based PC angle estimation app (Abbas et al., 2022; 5: 954497). In addition, each participant was required to complete a questionnaire in which crucial information about their experience and background and other therapeutically relevant data were captured.
RESULTS
Participating in the studies were 35 urology practitioners, including pediatric urologists, pediatric surgeons, and urologists. The mean absolute error (MAE), time required, and the inter-rater reliability were assessed. The results are provided in the table.
|
Measurement Modality |
Visual Inspection |
Goniometer |
Regular Mobile App. |
Artificial IntelligenceI-based Model |
P Value |
|
Mean absolute error (MAE) |
15.56° |
13.22° |
10.45° |
7.25° |
0.047 |
|
Time (Seconds) |
16 |
25 |
22 |
8 |
0.022 |
|
Inter-rater reliability; intraclass correlation (ICC) |
0.546 |
0.559 |
0.682 |
0.853 |
0.001 |
CONCLUSIONS
This AI-based PC measurement model demonstrated greater feasibility, consistency, and functionality compared to other available PC measurement instruments. The approach described here could greatly increase the precision with which surgeons and hypospadiology researchers quantify PC. Advanced machine learning and neural networks are being used in ongoing research to improve its performance even more.
08:46 - 08:49
S08-6 (OP)
Mahmoud M. MAREI 1, Abeer ABOALAZAYEM 1 and Mohamed Eyad BA'ATH 2
1) Cairo University Faculty of Medicine - Cairo University Hospitals, Paediatric Surgery, Cairo, EGYPT - 2) American Hospital Dubai, Paediatric Surgery & Urology, Dubai, UNITED ARAB EMIRATES
BACKGROUND & AIMS
Simulated training in Paediatric Surgery and Urology is gaining significance due to: (A) being a specialty of rare diseases affects individual surgeon's exposure to index cases; (B) subspecialty areas are not universally accessible; (C) Covid-19 affected elective surgery. Hypospadias is the index case/operation in Paediatric Urology, thus targeted training, via workshops and simulation, became necessary.
We hereby present our experience with the first launch of a silicone 3D-printed high-fidelity hypospadias model.
METHODS
Twenty-seven multinational trainees, under supervision of 15 instructors, completed the exercise. They were given a demonstrating seminar, showing 8 key steps. Each trainee filled a structured assessment form for the exercise quality and resemblance to live surgery. Each exercise was evaluated by an on-site supervising trainer, and two (blinded) independent remote assessors through photographs of the cardinal steps. The trainees and trainers rated each step (via Likert scale) from unsatisfactory (1/5) to excellent (5/5) for each of the following steps: (1)-degloving; (2)-urethral plate marking; (3)-incision; (4)-tubularisation; (5)-glanuloplasty; (6)-Dartos layer preparation; (7)-preputioplasty and (8)-skin closure.
RESULTS
Eleven-(40.7%) trainees were in years 1-3 of specialist training, 10-(37%) were in years 4-6, and 6 (22.2%) were beyond 6-years. Two-(7.4%) trainees had nil hypospadias experience, 16-(59.2%) previously assisted in procedures or performed steps, 5-(18.5%) performed whole procedures with guidance and 4-(14.8%) without guidance. Twenty-(74%) trainees and 15-(100%) instructors judged the model to accurately resemble the anomalous anatomy. Seventeen-(63%) trainees and 13-(86.6%) instructors rated needle-penetrability of the material ≥3/5, as compared to human tissue. Sixteen-(59%) trainees and 13-(86.6%) instructors rated suture holding of the material ≥3/5. Eleven-(73.3%) and 13-(86.6%) instructors rated sutures' evenness and edge coaptation ≥3/5.
CONCLUSIONS
Majority of instructors found this 3D-model able to mediate structured transferring of skills. Trainees demonstrated and reported adequate skill acquisition.
08:49 - 08:52
S08-7 (OP)
Yaqoub JAFAR 1, Melissa MCGRATH 1, Forough FARROKHYAR 2, Bruno LESLIE 1 and Luis BRAGA 1
1) Mcmaster children hospital, Pediatric urology, Hamilton, CANADA - 2) Mcmaster children hospital, Department of surgery and biostatics, Hamilton, CANADA
PURPOSE
To compare caudal anesthesia vs. dorsal penile block(DPB) on hypospadias repair complications.
MATERIAL AND METHODS
A superiority RCT including boys aged 6-48 months who underwent hypospadias repair by a single surgeon was conducted. Patients who could not be administered caudal or DPB and reoperations were excluded. Block randomization was employed with a 1:1 allocation ratio and a standardized anesthesia protocol. The primary outcome was development of UCF or glans dehiscence captured at 6-8 weeks, 6 and 12 months postoperatively. Secondary outcomes included postoperative pain and analgesic use in the hospital and at home using validated pain scales(FLACC, CHEOPS, PPPM, TPPPS), operative time(OpT), temperature at the start of the case, and induction time.
RESULTS
We enrolled 120 patients, and 14 withdrew. Of the 100 patients who completed follow-up, 50 had caudal and 50 DPB. Groups were balanced for baseline characteristics(table 1). The overall complication rate was 10 with 2 fistulas and 8 GD. We observed 8(16%) complications in the caudal group vs 2(4%) in the DPB(p=0.05). The mean OpT was 143 mins in the caudal vs. 122mins in the DPB group(p=0.04). Induction time was 23 mins vs. 16 mins, respectively(<0.01). Body temperature was 1oC lower in the caudal group. There was no difference in pain scales or analgesic use in the hospital or during the first 24hrs postoperatively.
Table 1.Baseline patient characteristics
| charactristics |
caudal n=50 (%) |
dorsal penile block n=50(%) |
| mean age at surgery (months) | 18.85±8.8 | 17.98±5.9 |
| Weight (kilograms) | 11.90 ± 2.26 | 11.63 ± 1.79 |
|
Location of Meatus Distal Midshaft Proximal |
38 (76) 10 (20) 2 (4) |
37 (74) 12 (24) 1 (2) |
CONCLUSIONS
The preliminary results of this RCT suggest that caudal blocks were associated with increased complication rates, increased OpT and induction time. DPB was as effective as a caudal block for pain management intraoperatively and in the first 24 hours postoperatively.
08:52 - 08:56
S08-8 (LOP)
Michael SENNERT 1, Christina PERSKE 2, Mohamed FAWZY 1, Johannes WIRMER 1 and Ahmed HADIDI 3
1) SANA KLINIKUM OFFENBACH, PEDIATRIC SURGERY, Offenbach Am Main, GERMANY - 2) University Medical Center Goettingen, Institute for Pathology, Goettingen, GERMANY - 3) Offenbach Klinikum, Pediatric Surgery and Urology, Seligenstadt, GERMANY
PURPOSE
Pre-operative Hormone Stimulation (PHS) is commonly used to increase the size of the glans and penis in Hypospadias Surgery. Molecular mechanisms are not well researched and the exact effects remain unclear. Some studies showed an increased vessel density in the foreskin, but the effect of PHS on the urethral plate and chordee has never been studied before. In this study, we examine the effects of PHS on the urethral plate using histological and histochemical stains.
MATERIAL AND METHODS
The urethral plate and the underlying tissues were excised to correct severe chordee in 16 children with proximal and perineal hypospadias with severe chordee: Eight patients had the urethral plate and chordee excised without PHS (Group A) and eight patients received PHS before surgery (Group B). Median age was 13 months (range 10-20). All the specimens were examined using hematoxylin-eosin stain and factor 8 antibodies. PHS was given before chordee excision in 8 patients due to Covid effect in delaying elective surgery.
RESULTS
Median vessel-density significantly increased from 65 to 82 vessels per mm2 (p<0.05). Median vessel diameter also increased significantly from 11 to 13µm (p<0.05). Although the thickness of the epithelial layer increased (from 98 to 110µm (p=0,16), this was not statistically significant. Also, there was no significant change in the dartos fascia thickness or androgen receptor count.
CONCLUSIONS
PHS caused significant increase in vessel density and diameter in the urethral plate. There was also increase in Epithelial and Dartos fascia thickness but we could not prove statistical significance.
|
vessel density /mm2 |
vessel diameter µm |
|
|
median in Group A |
65 |
11,195 |
|
median in Group B |
82 |
13,302 |
|
p-value |
0,003148385 |
0,013248688 |