This article reviews the establishment and progress of the Multidisciplinary Paediatric Robotic Program in a high-volume paediatric surgery department at Hôpital Necker-Enfants Malades, Paris, France. A major foundational principle of the program was to establish a safe and secure environment for patients and staff, both pre-operatively, intra-operatively and post-operatively. This founding principle when applied systematically has allowed increasing confidence across the program and service. The robotic platform allows for precision surgery when approaching tumours, with freedom of movement adapted to meticulous vascular and organ dissection. Surgical feasibility is based on tumour characteristics, pre-operative imaging, with a focus on vascular and organ involvement, considering goals of surgery and surgical experience. Case complexity has been gradually increased (where appropriate) through an iterative process. The future of surgery is robotic, and even more so image-guided surgery, and this synergy has been instrumental when approaching tumour surgery in children. The current principles that guide application of robot-assisted surgery in paediatric tumours are presented. With this blueprint, excellent oncological outcomes can be achieved while utilising a minimally invasive approach in children with selected endocrine, neuroblastic and renal tumours.

Introduction:Denys-Drash syndrome (DDS) is a rare disease typically associated with a triad of early onset nephrotic syndromes (NS), susceptibility to Wilms tumor (WT), and genitourinary structural defects. DDS is caused by Wilms' tumor suppression gene (WT1) variants, with the most frequent variants in exons 8 and 9. This study aimed to evaluate the long-term clinical outcomes and genotype-to-phenotype correlations in a large, multicenter cohort of children with typical DDS. Methods:We conducted a national retrospective study of all children diagnosed with a pathogenic variant in WT1 exons 8 or 9 in France between 2000 and 2022. Results:Fifty-eight children with DDS and variants in exons 8 (n = 23) and 9 (n = 35) of the WT1 gene were identified. Half of the children presented with NS (57% congenital, median age at presentation 0.3 years [interquartile range, IQR: 0.0-0.6]). Twenty-nine percent of children developed WT at a median age of 1.2 (0.5-2.2) years. Children with a variant in exon 8 developed NS much earlier than those with a variant in exon 9 (P = 0.0048), regardless of the type of genetic variation, leading to earlyier kidney failure (KF) (0.3 vs.1.4 years respectively; P = 0.0001) and higher mortality (35% vs 9%, P = 0.02). More than 90% of the truncating variants were located in exon 9 and were significantly associated with the occurrence of WT compared with the DNA-binding-site variants (P < 0.0015). Conclusion:In our cohort, children's DDS clinical trajectory was associated with exon localization. In the era of genomic newborn screening, depicting genetic risk is of utmost importance for personalized patient care.

BACKGROUND:Minimally invasive surgery for paediatric adrenal tumours has evolved, but robot-assisted laparoscopic adrenalectomy (RALA) in children remains poorly studied. The current prospective study aims to demonstrate the safety and efficacy of RALA in treating children with adrenal tumours. METHODS:A prospective institutional analysis of children presenting with neuroblastic and endocrine tumours treated with RALA was undertaken over a six year-period. For each child, clinical parameters were collected relating to diagnosis, surgery and outcomes. RESULTS:A total 50 RALA were performed; 23 for unilateral neuroblastic tumours (87 % neuroblastomas) and 27 for endocrine tumours. Eight neuroblastic tumours (35 %) had image-defined risk factors (all due to tumour invading the renal pedicle). Median length of stay was two days. Resection margins were macroscopically clear in all cases. After median follow-up of 2.9 years (1.6-3.9), two children are under treatment for metastatic relapse (high-risk disease) and three died due to refractory disease. Sixteen children had endocrine tumours: pheochromocytoma (n = 13), or bilateral nodular adrenocortical hyperplasia with Cushing's syndrome (n = 14). One child required non-emergent conversion, and one complication occurred (grade IIIb) after median follow-up of 3.3 years (1.0-5.7). CONCLUSIONS:The current study is the largest reported experience in the literature and confirms the safety and effectiveness of RALA in carefully selected children with adrenal tumours. Through an iterative process and in the setting of a dedicated paediatric robotic surgical team indications have been clarified and extended. The current study confirms RALA has particularly utility in patients with severe disease (IDRF + metastatic neuroblastomas) or genetic predisposition syndromes.

To the Editor: Ovarian torsion reveals ovarian mass in 51% to 84% of cases1 in the pediatric population. Clinical recommendations suggest conservativemanagementwithdetorsion, leaving time for tumormarker dosage and proper imaging. Diagnosis of ovarian malignancy relies mainly on tumor markers that can exceptionally be false-positive. Most of the tumors encountered present as solid ormixed lesions upon ultrasound, except teratoma and juvenile granulosa cell tumor (JGCT) that may be cystic.2,3 Surgical strategy, conservative or not, is then chosen according to these complementary exams, keeping inmind the lowmalignancy prevalence in the pediatric population with adnexal torsion.4 We report a very unusual case of false-positive inhibinB level, which led to inappropriate oophorectomy. A 15-year-old female presented at the emergency ward with adnexal torsion. She had her menarche at the age of 11, with regular cycles and no prior medical history except for a recent episode of 5months of secondary amenorrhea. Ultrasound showed an enlarged and congestive left ovary with a 5-cm simple cyst (Figure 1). Laparoscopy showed a left adnexal torsion with a voluminous ischemic ovary. The cyst ruptured during detorsion and a serous fluid sample was sent for pathological analysis. Five days later, preoperative inhibin B dosage came back at 1025.34 pg/mL. The rest of the hormonal work-up was normal, including alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) levels (Table 1). A pelvic magnetic resonance imaging (MRI) on day 7 postoperatively showed a 25-mm cyst on the left ovary and a normal right ovary. Given the elevated inhibin B level, cystic JGCT was highly suspected. A second opinion in a tertiary cancer care center proposed close monitoring, including serial inhibin B levels and pelvic ultrasound. Peritoneal cytology came back negative. Inhibin B levels remained elevated in another lab, and two pelvic ultrasounds done 16 and 21 days after detorsion showed an unchanged unilocular cystic lesion on the left ovary. Multidisciplinary local and regional tumor board discussions agreed on left oophorectomy because of the persistent elevated inhibin B levels associated with a cystic lesion. The intraoperative rupture of the cyst argued against monitoring. Intraoperatively, the left ovary appeared normal apart from the rupture site that was still visible. Eighteen hours postoperatively, inhibin B dosage was still elevated. The pathology report concluded at a hemorrhagic ovary containing normal follicles without tumoral site. The possibility of a heterophilic antibodies (HA) interference was raised as the inhibin B results were still elevated postoperatively with no evidence of tumor. Two samples were retested after pretreatment with heterophilic blocking tubes revealing normal levels of inhibin B, confirming an HA interference. One sample was also sent to another laboratory using the AnsLabs method and came back normal for inhibin B. HA are a rare cause of false-positive hormonal immunoassay, with an estimated prevalence from 0.4% to 0.5%.5,6 This interference concerns all hormonal markers including inhibin A.7 HA are considered to occur naturally (typically of human origin) and are able to react with antibodies from multiple species being weakly polyspecific. No blocking reagent/method is completely successful in preventing such interference. Hormonal tests are relying on different methodologies andmay differ from a laboratory to another. During the entire follow-up, high inhibin results were obtained from two laboratories. However, without knowledge of it, the same technique was used in both laboratories: Inhibin B Gen II of Beckman Coulter (Immunotech s.r.o., Prague). An interference testing using a HAMA (human anti-mouse antibodies) Elisa test was also performed and did not show the presence of HAMA

Elisa Zambaiti , Salvatore Cascio, Gloria Pelizzo, Alexander Siles Hinojosa, Juan Carlos de Augustin Asensio, Caroline Fortmann, Martin Lacher, MariaMalowiecka, Piotr Czauderna, ChristophArneitz, Holger Till, Mathilde Glenisson, Arnaud Bonnard, Anders Telle Hoel, Kristin Bjørnland, Maria Hukkinen, Godosis Demetrios, Nikolaos Zavras, Helena Reusens, Henri Steyaert, Andrea Pevere, Ophelia Aubert and Luca Pio*

Introduction The use of interventional radiology (IR) in the treatment of pediatric solid tumors has markedly increased over the last three decades. However, data on effectiveness of IR-techniques, such as embolization/ablation, are scarce. In this systematic review and meta-analysis, we examined the outcomes of IR-procedures in the treatment of solid tumors in children. Materials and Methods Using a defined search strategy, we searched for studies reporting the use of IR-techniques for pediatric solid tumors from 1980 to 2017. Reports with less than three patients, review, and opinion articles were excluded. The study was conducted under preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. We analyzed dichotomous and continuous variables by appropriate statistical methods. Results Of 567 articles screened, 21 papers met the inclusion criteria (12 retrospective, 7 prospective, and 2 randomized-control trials). Many of the analyzed papers described relatively small cohorts of patients. IR-guided procedures were mainly rescue procedures to treat primarily unresectable tumors, local recurrences, or metastases. Inclusion/exclusion criteria and success definition were not specified in most reports. Major side effects were documented in 17/286 (6%) infants, while minor side effects were self-limiting in most patients. Six studies had a comparison between tumor embolization (127 infants) to surgery or chemotherapy without IR-procedures (113 controls). The meta-analysis showed lower mortality (16 vs. 47%) and surgical time for resection (206 vs. 250 m), higher 2-year tumor-free survival (82 vs. 36%), and favorable histology in IR group (p < 0.001 for all). Conclusion IR-guided techniques are promising in the treatment of pediatric solid tumors. Further prospective (randomized) trials are needed to clarify efficacy.