Parallel Meeting on Wednesday 19, April 2023, 16:55 - 17:40
Matthijs FITSKI 1, Guus BÖKKERINK 1, Marc WIJNEN 1, Cornelis VAN DE VEN 1, Annemieke LITTOOIJ 2, Aart KLIJN 3 and Alida VAN DER STEEG 1
1) Princess Máxima Center for pediatric oncology, Pediatric Surgery, Utrecht, NETHERLANDS - 2) University Medical Center Utrecht/Wilhelmina Children's Hospital, Radiology and Nuclear Medicine, Utrecht, NETHERLANDS - 3) University Medical Center Utrecht/Wilhelmina Children's Hospital, Pediatric Urology, Utrecht, NETHERLANDS
Surgical resection of renal tumors in children is an essential part of treatment. To reduce complications and improve surgical understanding of renal arterial vasculature, a high-resolution Non-Contrast Magnetic Resonance Angiography (NC-MRA) sequence was implemented. We assessed NC-MRA for the preoperative planning of Wilms Tumor surgery.
PATIENTS AND METHODS
The preoperative MRI scans of all patients with a kidney tumor between October 2019 and July 2021 were retrospectively assessed by two pediatric surgeons and one pediatric urologist. The surgeons assessed their understanding of the aorta, renal artery, extraparenchymal artery and intraparenchymal artery in the T2-Weighted sequence (T2W), Contrast-Enhanced MRA (CE-MRA) and NC-MRA. Moreover, they assessed whether the sequence helped them during the preoperative planning. All assessments were based on a 5-point scale. Additionally, the scans of 10 patients undergoing a surgical resection were assessed prospectively by one of the performing surgeons.
37 patients were included in the retrospective assessment. The median scan time for NC-MRA was 209 seconds. The NC-MRA visualized the intraparenchymal arteries more accurately than the CE-MRA (3 vs 1 out of 5). There was no significant difference between the scoring of the NC-MRA and T2W at this anatomical region. The NC-MRA sequence was considered useful during surgical planning (4 out of 5) but there was no significant difference from the T2W sequence. During the prospective assessment, the NC-MRA improved the differentiation of vessels at the level of the intraparenchymal arteries.
NC-MRA is considered a helpful additional imaging sequence for the preoperative planning of Wilms Tumor surgery, especially for nephron-sparing surgery.
Yann CHAUSSY 1, Lorédane SALVI 1, Olivier HILD 1, Pierre BERRIET 2, Julien HENRIET 2 and Frédéric AUBER 1
1) CHRU Jean Minjoz, Paediatric Urology, Besancon, FRANCE - 2) Université de Bourgogne Franche-Comté, FEMTO-ST, Besançon, FRANCE
Wilms’ tumor is the most common type of malignant kidney tumor in children. Three-dimensional reconstructions can be useful to assist surgeons with the surgical planning phase, to select patients for nephron sparing surgery or to counsel patients and their families. However, manual segmentations are time-consuming. The aim of this study is to use artificial intelligence to automatize the segmentation of Wilms tumors and kidneys.
MATERIAL AND METHODS
The segmentation of Wilms’ tumors and kidneys was initially performed using the U-Net convolutional neural network (CNN). Then, the segmentation was performed using the same U-Net CNN trained with an innovative method called OV2ASSION. In this method, the system needs a variable number of sectional CT-images manually segmented for the training phase. The results are compared with inter-individual variability, obtained by manual segmentations performed by two experts, using the Dice similarity index.
The process was performed on 14 CT scans. The Dice indexes for segmentation using U-Net were 0.69 and 0.27 for Wilms’ tumor and pathologic kidney respectively. The Dice indexes were significantly increased when the U-Net was trained with OV2ASSION method. The CNN reached the same precision than an expert when a fifth of all segmentations was manually performed, reducing the expert’s intervention time by 80%.
The automatic segmentation remains a challenge in the field of image processing, particularly for tumor in children. Artificial intelligence tools are promising to address this challenge. The method presented is not fully automatic but allows a significant reduction of the expert’s intervention time.
Ahmed ABDELHALIM 1, Ahmed NASHAT 2, Rasha ABOUELKHEIR 3, Israa SHARABY 4, Ahmed ELKSAS 4, Hossam BALAHA 4, Mohamed SHEHATA 4, Mallorie GAYHART 5, Ali MAHMOUD 4, Norah ALGHAMDI 6, Mohammed GHAZAL 7, Ashraf KHALIL 8, Ahmed ELMAHDY 3, Ayman EL-BAZ 4 and Ahmed MOSBAH 2
1) Mansoura Urology and Nephrology Center, West Virginia University, Department of Urology, Mansoura, EGYPT - 2) Mansoura Urology and Nephrology Center, Department of Urology, Mansoura, EGYPT - 3) Mansoura Urology and Nephrology Center, Department of Radiology, Mansoura, EGYPT - 4) University of Louisville, Bioengineering Department, Louisville, USA - 5) Berea College, Department of Biology, Berea, USA - 6) Princess Nourah Bint Abdulrahman University, Department of Computer Sciences, Riyadh, SAUDI ARABIA - 7) Abu Dhabi University, Computer and Biomedical Engineering Department, Abu Dhabi, UNITED ARAB EMIRATES - 8) Zayed University, College of Technological Innovations, Abu Dhabi, UNITED ARAB EMIRATES
Preoperative chemotherapy (PC) is used systematically by the International Society of Pediatric Oncology to treat childhood renal tumors (CRT). However, 53% of tumors do not have substantial size reduction after PC and 5-12% show progressive disease. We sought to create a computer-aided prediction system to help identify tumors that are less likely to respond to PC based on pre-therapy contrast-enhanced CT (CECT).
MATERIAL AND METHODS
A tertiary center database was reviewed for children <18 years diagnosed with Wilms' tumor and received PC between 2000-2021. Patients were excluded if pre- and post-PC CECT could not be retrieved. According to the Response Evaluation Criteria in Solid Tumors, >30% tumor size reduction was considered a favorable response. To create the prediction model, the following steps were followed: tumor delineation in the three contrast phases; extraction of the shape, texture and functionality-based features; integration (fusion) of the features extracted and selection of the prediction model with the highest diagnostic performance. K-fold cross-validation allowed all data parts to be presented in the training and testing phases.
A total of 63 tumors with a mean patient age of 4.31±2.82 years were used to train and test the prediction model. Patients were treated with 6-8 weeks of vincristine/actinomycin-D combination. Favorable response to PC was observed in 46 (75.4%) tumors. Among other machine learning classifiers, support vector machine had the best diagnostic performance with 95.24% overall accuracy, 95.65% sensitivity of and 94.12% specificity.
Based on pre-therapy CECT, computer-aided prediction systems can help identify CRT that are less likely to respond to PC with excellent accuracy. These tumors can be offered upfront surgery, and therefore avoiding the disadvantages of PC and individualizing treatment plans.
Mathilde GLENISSON 1, Mathilde GRAPIN 2, Thomas BLANC 1, Véronique MINARD 3, Daniel ORBACH 4, Laurence HEIDET 2, Olivia BOYER 2, Guillaume DORVAL 5 and Sabine SARNACKI 1
1) Hôpital Necker-Enfants Malades, Pediatric surgery and Urology, Paris Cedex 15, FRANCE - 2) Hôpital Necker-Enfants Malades, Pediatric Nephrology, Paris Cedex 15, FRANCE - 3) Institut Gustave Roussy, Pediatric and Adolescent Oncology, Villejuif, FRANCE - 4) Institut Curie, Pediatric Oncology SIREDO Oncology Center (Care, Innovation and Research for Children and AYA with Cancer), Paris, FRANCE - 5) Hôpital Necker-Enfants Malades, Molecular Genetics, Paris Cedex 15, FRANCE
Denys Drash syndrome (DDS) is caused by WT1 mutations and is associated with a high risk of Wilms tumour (WT) and diffuse mesangial sclerosis leading to end-stage renal disease (ESRD). Onset of disease is variable, and there is a wide clinical spectrum with a genotype to phenotype correlation.The aim of the study was to assess the impact of WT on the outcomes of children with DDS.
MATERIAL AND METHODS
Patients with a mutation of WT1 in exon 8 or 9 were included between 2001 and 2020. Other mutation were excluded. Charts were reviewed retrospectively.
Thirty children were identified, 8 with a Wilms tumour (WT+ group), and 22 without (WT- group). Median age at WT diagnosis was 15 months (IQR 11-20).Only one patient had a diagnosis of DDS preceding their diagnosis of WT. Patients in the WT+ group developed later ESRD at a median age of 1.5 years (IQR 1.2-7.4) versus 0.5 years (IQR 0.3-1) (p=0.01). Overall survival was better in the WT+ group (Log-rank: p=0.02). Median age at last follow-up was 7.3 years (IQR 0.8-10.7); 11.1 years (IQR 6.6-15.4) in the WT+ group and 4.5 years (IQR 0.4-8.8) in the WT- group.
Patients with DDS and WT have a later progression to ERSD and a better overall survival. In the WT- group, early ERSD leads to a poor prognosis with excess mortality, which may relates to the morbidity of neonatal dialysis and complications linked to the of nephrotic syndrome.
Astgik PETROSYAN 1, Valentina VILLANI 1, Paola AGUIARI 1, Mahdi MIN 1, Matthew THORNTON 2, Brendan GRUBBS 3, Roger DE FILIPPO 1, Kevin LEMLEY 4, Sargis SEDRAKYAN 1, Gregory SHACKLEFORD 2, Anat ERDREICH-EPSTEIN 2, Stefano DA SACCO 2 and Laura PERIN 2
1) Children's Hospital Los Angeles, Urology, Los Angeles, USA - 2) Children's Hospital Los Angeles, Los Angeles, USA - 3) University of Southern California, Los Angeles, USA - 4) Children's Hospital Los Angeles, Nephrology, Los Angeles, USA
Wilms Tumor (WT) is the most common pediatric renal cancer. Growing evidence links WT to aberrant nephrogenesis. While studies highlighted the genetic complexity of WT, little is known about the molecular mechanisms that regulate WT development. Here we report that uncommitted nephrogenic progenitors (NPs) expressing SIX2 and CITED1 (the master regulators of renal development) present characteristics of cancer stem cells (CSCs) and are the ones driving WT. We have also studied the role of integrins in these NPs in regulating WT development.
MATERIAL AND METHODS
WT and human fetal kidney (hFK) samples were histologically analyzed, digested to single-cell suspension, incubated with Smartflare-probe to isolate SIX2+CITED1+ cells, and processed for RNA-seq, single-cell RNA-seq and spatial transcriptomics. Xenografts of WT-NPs and hFK-NPs were generated and tumor formation was assessed. Analyses of mechanisms that regulate self-renewal vs. differentiation were performed in vitro and in vivo. Knockdown with miREs against SIX2 and CITED1 was performed on WT-NPs and processed for RNA-seq.
By comparing NPs from different WT subtypes and NPs from hFK we identified that cells expressing SIX2 and CITED1 fulfill CSC criteria, reliably recapitulating WT in transplantation studies. We showed that self-renewal vs. differentiation of SIX2+CITED1+ WT CSCs is regulated by the interplay between integrins ITGB1 and ITGB4. WT transplantation studies show that blocking ITGB1 or ITGB4 leads to higher number of SIX2+CITED1+ cells in the xenografts. Knockdown of SIX2 and CITED1 increased expression of kidney differentiation markers LHX1, WNT7B, PODXL, MECOM, reduced expression of nephrogenic markers MEOX1, TMEM100, EYA1, MAYFB, and increased expression of ITGB1, ITGB4, and LAMA5.
These studies define SIX2+CITED1+ cells as the nephrogenic CSCs of WT, where ITGB1 and ITGB4 interplay may play a role in self-renewal vs. differentiation and serve as a potential target for new strategies to treat WT.
Christopher JAEGER 1, Andrea BALTHAZAR 1, Rachel SAUNDERS 1, Monah JAVIDAN-NEJAD 2, Candace CHUNG 1, Judith VESSEY 3, Richard LEE 1 and Hsin-Hsiao WANG 1
1) Boston Children's Hospital, Urology, Boston, USA - 2) Harvard University, Cambridge, USA - 3) Boston Children's Hospital, Medical, Surgical and Behavioral Health Programs, Boston, USA
Genitourinary Rhabdomyosarcoma (GU-RMS) often requires multimodal therapy including radiation, chemotherapy, and radical surgeries to maximize disease control. The long-term effects of the disease and associated treatments is unclear. We seek to investigate the long-term genitourinary quality of life (QoL) for survivors of pediatric GU-RMS, including urinary function, fertility, sexual function, and associated QoL.
MATERIAL AND METHODS
In total, 14 (43% female, median age=32.5 years [IQR=23.25 - 39.25], 2 bladder, 1 cervical, 5 paratesticular, 3 vaginal, 2 pelvic, 1 prostate RMS) agreed to interview about impact of childhood GU-RMS treatment on current QoL. A semi-structured interview guide based on Long-Term Service and Support QoL conception model (LTSS HRQOL), and grounded in GU-RMS experiences was created. Categories included urinary function, sexual function, general health, mental health, and social dynamics. Two coders independently coded using thematic analysis.
Using directed content analysis, three themes specific to genitourinary functions emerged: fertility preservation, sexual health communication with partners, and education of GU-RMS impact during and after treatment. Specifically, participants discussed an interest in better understanding fertility preservation options, and post-treatment effects on their anatomy. They noted that knowledge of their ability to conceive impacted their desire to have children. Participants also have challenges related to if, when or how to communicate details of their sexual health with a partner. Across these themes, participants reported insufficient knowledge regarding GU-RMS treatment and its impact on current and future functions. Specific areas of concern were anatomical changes, fertility and pregnancy expectations, and survivorship.
For GU-RMS, significant urinary and sexual function concerns would be important to address with long-term survivorship. Clinicians can potentially improve their QoL through gradually educating patients about expectations for treatment, fertility preservation options, and long-term effects of treatment, at relevant stages in a patient's life.
Ketaki GHARPURE and Naima SMEULDERS
Great Ormond Street Hospital, Urology, London, UNITED KINGDOM
Urothelial neoplasms are a rare entity in children. For solitary polypoidal lesions, transurethral resection is the gold standard. Bladder perforation and bleeding are recognised complications, with perforation reported in up to 58% in some series. In this video, we demonstrate a dual cystoscopic approach per urethra and suprapubically to treat a solitary polypoidal bladder mass.
MATERIAL AND METHODS
Under cystoscopic vision (Storz® 14Fr) suprapubic access is established (Boston Scientific® Nephromax, 30Fr Amplatz sheath), allowing synchronous suprapubic cystoscopy (Wolf 20.8Fr). Traction by grasping forceps of the polyp into the vesical lumen by one scope permits precise application of the laser fibre (Cook® Holmium YAG 2.0J 10Hz, 360 fibre) along the margin of the stalk by the second scope without excavating through the detrusor.
A 13 year-old boy presented with haematuria. Ultrasound and MRI identified a solitary polypoidal mass on the right lateral bladder wall. Per urethra and suprapubic access created a 90° angle between the two scopes enabling precise excision without blood loss or perforation in 38 minutes operative time. The polyp was extracted in one piece through the Amplatz sheath. The patient was discharged on post-operative day 1 with a suprapubic catheter on free drainage for 7 days. Histology revealed a low grade papillary urothelial carcinoma stage pTa, completely resected.
We propose the TUPCRBT to alleviate the high risk of perforation associated with TURBT. Synchronous urethral and suprapubic percutaneous access achieves surgical triangulation between the cystoscopes. The use of traction enables safe and yet complete resection.