Laparoscopic Treatment of Wilms' Tumor: Criteria of SIOP-UMBRELLA Protocol may be Updated.

INTRODUCTION: Total nephrectomies for the treatment of Wilms' tumor (WT) are more and more performed by laparoscopy, although indications for this approach following the UMBRELLA guidelines are currently very restrictive. The purpose of this study was to assess the compliance to the criteria of the UMBRELLA protocol for minimally invasive approach of WT. METHODS: This retrospective multicenter study included children operated on by laparoscopic total nephrectomy for suspected WT before 2020. Imaging was reviewed centrally. RESULTS: Fifty-six patients (50 WT and 6 nephrogenic rests) were operated on at a median age of 3.3 ± 2.6 years. Thirteen (23%) patients had metastasis at diagnosis. The mean operative time was 213 ± 84 min. There were eight (14.3%) conversions and five peroperative complications. A local stage III was confirmed in seven (12.5%) cases, including two for tumor rupture. Only one (1.8%) of the procedures followed the SIOP-UMBRELLA indications for laparoscopy. The criterion "ring of normal parenchyma" was met only once. Conservative surgery seemed possible in ten (17.9%) cases. The extension of the tumor beyond the ipsilateral edge of the vertebra after chemotherapy and a volume over 200 mL were associated with an increased risk of conversion (p = 0.0004 and p = 0.001 respectively). After a mean follow-up of 5.2 ± 4.0 years, although there was no local recurrence, one death occurred due to metastatic progression at 15 months postoperatively. CONCLUSIONS: The laparoscopic approach of WT beyond the UMBRELLA recommendations was feasible with low risk of local recurrence. Its indications may be updated and validated.

Care pathways in childhood neurodevelopmental disorders: Toward greater awareness of KBG syndrome among pediatricians.

INTRODUCTION: KBG syndrome is an autosomal dominant, polymalformative genetic syndrome that is mainly associated with neurodevelopmental and learning disorders, intellectual disability, behavioral disorders, and epilepsy as well as characteristic dysmorphic features, short stature, and ENT (ear, nose, and throat) abnormalities. However, the diagnostic pathway of these individuals is an element that has not been broadly evaluated. The main aim of this study was therefore to characterize the diagnostic pathway for these individuals, by assessing the different healthcare professionals involved and the main referral elements. METHOD: This was a multicenter, retrospective, descriptive study. A cohort of 30 individuals with KBG syndrome who were followed up at Poitiers University Hospital and Bordeaux University Hospital we recruited. RESULTS: Pediatricians were the main healthcare professionals who referred individuals for genetic consultation, and the main reason for referral was an assessment of learning delays or intellectual disability, in association with other abnormalities. CONCLUSION: Pediatricians play a crucial role in the diagnostic guidance of individuals with KBG syndrome, and the main reason for referral remains the assessment of a learning delay or intellectual disability. Healthcare professionals must therefore remain attentive to the child's development and the various anomalies associated with it, in particular characteristic dysmorphic features, behavioral disorders, and statural growth.

No lockdown for pediatric burns.

BACKGROUND: The health crisis related to the COVID-19 pandemic led to an unprecedented situation in France: complete lockdown. The population had to live confined with their families, which often meant that parents telecommuted while caring for their children. However, daily risks remained more than ever at the forefront. The aim of this study was to assess the epidemiology of burns among children during three different periods of family time: school time, vacation, and lockdown. METHODS: A single-center retrospective study was conducted at Tours University Hospital. All pediatric surgical emergency room visits recorded from February 10, 2020 to March 31, 2020 were included. The three aforementioned periods were assessed. RESULTS: During lockdown there were significantly more burns compared to other injuries (p = 0.004). Preschool-age children suffered significantly more from burns during the same period (p = 0.029). There were no significant differences for nursery school (p = 0.522), primary school (p = 0.519), middle school (p = 0.613), and high school (p = N) children. CONCLUSION: This study underlines the need to establish a targeted prevention campaign geared toward a complicated geopolitical situation a pandemic that might occur again.

Cumulative and potential synergistic effects of seven different bisphenols on human granulosa cells in vitro?

Bisphenol (BP) structural analogues of BPA are widely used. Previous studies showed similar effects of BPA and BPS on reproduction in several species including human. We hypothesised that the similar effects of several bisphenols (BPs) could accumulate in granulosa cells (GCs) and affects steroidogenesis. This study investigated the effects of seven BP analogues and their equimolar cocktail on human granulosa cells (hGC) and assessed BPA, BPS, BPF and BPAF level exposures in the follicular fluid of 277 women undergoing Assisted Reproductive Technology. The hGCs were recovered after women oocyte punctures and treated with the seven BP analogues (BPS, BPA, BPAF, BPF, BPAP, BPE and BPB) or their equimolar cocktail of 7 × 1.43 or 7 × 7.14 µM for each of the seven BPs, the sum of BPs reaching 10 ("∑BPs 10 µM"), or 50 µM ("∑BPs 50 µM"), respectively. Oestradiol and progesterone secretion, cell proliferation, viability and expression of steroidogenic enzymes were investigated. Progesterone secretion was decreased by 6 BPs 10 µM and the cocktail "∑BPs 10 µM", (-17.8 to -41.3%) and by all seven BPs 50 µM and "∑BPs 50 µM" (-21.8 to -84.2%). Oestradiol secretion was decreased only by 50 µM BPAF and BPAP (-37.8% and -44%, respectively), with corresponding decreases in CYP17A1 and CYP19A1 gene expression. Cellular proliferation was decreased after treatment with 50 µM BPAF (-32.2%), BPAP (-29%), BPB (-24%) and the equimolar cocktail "∑BPs 50 µM" (-33.1%). BPB (50 µM) and the cocktail "∑BPs 50 µM" increased HSD3B2 mRNA expression. At least one BP was detected in 64 of 277 (23.1%) women follicular fluids. Similar effects of the seven BPs or their cocktail were observed on progesterone secretion and/or on cell proliferation, suggesting cumulative effects of BPs. Our results highlight the urge to consider all BPs simultaneously and to further investigate the potential additive or synergistic effects of several BPs.

Bisphenol A and bisphenol S both disrupt ovine granulosa cell steroidogenesis but through different molecular pathways.

BACKGROUND: Ovarian granulosa cells (GC) are essential for the development and maturation of a proper oocyte. GC are sensitive to endocrine disruptors, including bisphenol A (BPA) and its analogue bisphenol S (BPS), plasticisers present in everyday consumer products. BPA exhibits greater binding affinity for the membrane oestrogen receptor (GPER) than for the nuclear oestrogen receptors (ERα and ERß). Here, we analysed the effects of BPA and BPS on the steroidogenesis of ovine GC in vitro, as well as their early mechanisms of action, the ovine being a relevant model to study human reproductive impairment. Disruption of GC steroidogenesis might alter oocyte quality and consequently fertility rate. In addition, we compared the effects of a specific GPER agonist (G-1) and antagonist (G-15) to those of BPA and BPS. Ewe GC were cultured with BPA or BPS (10 or 50 µM) or G-1 (1 µM) and/or G-15 (10 µM) for 48 h to study steroidogenesis. RESULTS: Both BPA and BPS (10 µM) altered the secretion of progesterone, however, only BPS (10 µM) affected oestradiol secretion. RNA-seq was performed on GC after 1 h of culture with BPA or BPS (50 µM) or G-1 (10 µM), followed by real-time PCR analyses of differentially expressed genes after 12, 24 and 48 h of culture. The absence of induced GPER target genes showed that BPA and BPS did not activate GPER in GC after 1 h of treatment. These molecules exhibited mainly independent early mechanisms of action. Gene ontology analysis showed that after 1 h of treatment, BPA mainly disrupted the expression of the genes involved in metabolism and transcription, while BPS had a smaller effect and impaired cellular communications. BPA had a transient effect on the expression of CHAC1 (NOTCH signalling and oxidative balance), JUN (linked to MAPK pathway), NR4A1 (oestradiol secretion inhibition), ARRDC4 (endocytose of GPCR) and KLF10 (cell growth, differentiation and apoptosis), while expression changes were maintained over time for the genes LSMEM1 (linked to MAPK pathway), TXNIP (oxidative stress) and LIF (cell cycle regulation) after 12 and 48 h, respectively. CONCLUSION: In conclusion, although they exhibited similar effects, BPA and BPS impaired different molecular pathways in GC in vitro. New investigations will be necessary to follow the temporal changes of these genes over time, as well as the biological processes involved.

Bisphenol S Impairs Oestradiol Secretion during In Vitro Basal Folliculogenesis in a Mono-Ovulatory Species Model.

Bisphenol S (BPS) affects terminal folliculogenesis by impairing steroidogenesis in granulosa cells from different species. Nevertheless, limited data are available on its effects during basal folliculogenesis. In this study, we evaluate in vitro the effects of a long-term BPS exposure on a model of basal follicular development in a mono-ovulatory species. We cultured ovine preantral follicles (180−240 µm, n = 168) with BPS (0.1 µM (possible human exposure dose) or 10 µM (high dose)) and monitored antrum appearance and follicular survival and growth for 15 days. We measured hormonal secretions (oestradiol (at day 13 [D13]), progesterone and anti-Müllerian hormone [D15]) and expression of key follicular development and redox status genes (D15) in medium and whole follicles, respectively. BPS (0.1 µM) decreased oestradiol secretion compared with the control (−48.8%, p < 0.001), without significantly impairing antrum appearance, follicular survival and growth, anti-Müllerian hormone and progesterone secretion and target gene expression. Thus, BPS could also impair oestradiol secretion during basal folliculogenesis as it is the case during terminal folliculogenesis. It questions the use of BPS as a safe BPA substitute in the human environment. More studies are required to elucidate mechanisms of action of BPS and its effects throughout basal follicular development.

Bisphenol S Alters the Steroidome in the Preovulatory Follicle, Oviduct Fluid and Plasma in Ewes With Contrasted Metabolic Status.

Bisphenol A (BPA), a plasticizer and endocrine disruptor, has been substituted by bisphenol S (BPS), a structural analogue that had already shown adverse effects on granulosa cell steroidogenesis. The objective of this study was to assess the effect of chronic exposure to BPS, a possible endocrine disruptor, on steroid hormones in the ovary, oviduct and plasma using the ewe as a model. Given the interaction between steroidogenesis and the metabolic status, the BPS effect was tested according to two diet groups. Eighty adult ewes were allotted to restricted (R) and well-fed (WF) groups, that were further subdivided into two subgroups. Ewes were exposed to 50 µg BPS/kg/day in their diet (R50 and WF50 groups) or were unexposed controls (R0 and WF0 groups). After at least 3 months of BPS exposure, preovulatory follicular fluid, oviduct fluid and plasma were collected and steroid hormones were analyzed by gas chromatography coupled with tandem mass spectrometry (GC-MS/MS). A deleterious effect of restricted diet on the volume of oviduct fluid and numbers of pre-ovulatory follicles was observed. Exposure to BPS impaired estradiol concentrations in both follicular and oviduct fluids of well-fed ewes and progesterone, estradiol and estrone concentrations in plasma of restricted ewes. In addition, a significant interaction between metabolic status and BPS exposure was observed for seven steroids, including estradiol. In conclusion, BPS acts in ewes as an endocrine disruptor with differential actions according to metabolic status.

Chronic low BPS exposure through diet impairs in vitro embryo production parameters according to metabolic status in the ewe.

Bisphenol A (BPA), an endocrine disruptor, has been replaced by structural analogues including bisphenol S (BPS). BPA and BPS exhibited similar effects regarding reproductive functions. Moreover, metabolic status and lipid metabolism are related to female fertility and could worsen BPS effects. The objective was to determine BPS in vivo effects on folliculogenesis and embryo production after chronic exposure through diet, and the influence of metabolic status in adult ewes. Sixty primiparous 2.5 year-old ewes, undergoing a restricted or well fed diet, were exposed to BPS (0, 4 or 50 µg/kg/day) for at least three months. After hormonal oestrus synchronisation and ovarian stimulation, ewes were subjected to ovum pick-up (OPU) procedures to collect immature oocytes, that underwent in vitro maturation, fertilisation and embryo production. Body weight, body condition score and plasma glucose were higher in well-fed compared to restricted ewes, while plasma NEFA was lower during the 4-5 months after the beginning of the diets. Plasma progesterone levels increased on day 5 before OPU session in well-fed compared to restricted ewes. No effect of BPS dose was observed on follicle population, plasma AMH levels and embryo production numbers and rates. However, a significant diet x BPS dose interaction was reported for cleaved embryos, > 4-cell embryos, blastocyst and early blastocyst numbers, and plasma triiodothyronine levels. Our study showed that a contrasted diet did not affect follicle population nor embryo production in adult ewes but could affect the quality and progesterone secretion of the corpus luteum. Chronic low BPS exposure had no effect on follicular population and oocyte competence. Nevertheless, the significant diet x dose interactions observed on embryo production suggest that BPS effect is modulated by metabolic status. Further studies are required to assess the risk of BPS exposure for public reproductive health.

Robotic Surgery in Pediatric Oncology: Lessons Learned from the First 100 Tumors-A Nationwide Experience.

BACKGROUND: While robotics has become commonplace in adult oncology, it remains rare in pediatric oncology due to the rarity of childhood cancers. We present the results of a large nationwide experience with robotic oncology, with the aim of providing practical and feasible guidelines for child selection. METHODS: This was a prospective analysis performed over a period of 4 years. Treatment was delivered according to the Société Internationale d'Oncologie Pédiatrique/International Society of Paediatric Oncology Europe Neuroblastoma Group (SIOP/SIOPEN) protocols. Indications were approved by a certified tumor board. RESULTS: Overall, 100 tumors were resected during 93 procedures (abdomen, 67%; thorax, 17%; pelvis, 10%; retroperitoneum, 6%) in 89 children (56 girls). The median age at surgery was 8.2 years (range 3.6-13); 19 children (21%) harbored germinal genetic alterations predisposing to cancer. No intraoperative tumor ruptures occurred. Seven conversions (8%) to an open approach were performed. Neuroblastic tumors (n = 31) comprised the main group (18 neuroblastomas, 4 ganglioneuroblastomas, 9 ganglioneuromas) and renal tumors comprised the second largest group (n = 24, including 20 Wilms' tumors). The remaining 45 tumors included neuroendocrine (n = 12), adrenal (n = 9), germ-cell (n = 7), pancreatic (n = 4), thymic (n = 4), inflammatory myofibroblastic (n = 4), and different rare tumors (n = 5). Overall, 51 tumors were malignant, 2 were borderline, and 47 were benign. The median hospital stay was 3 days (2-4), and five postoperative complications occurred within the first 30 days. During a median follow-up of 2.4 years, one child (Wilms' tumor) presented with pleural recurrence. One girl with Wilms' tumor died of central nervous system metastasis. CONCLUSIONS: Robotic surgery for pediatric tumors is a safe option in highly selected cases. Indications should be discussed by tumor boards to avoid widespread and uncontrolled application.

The Potential and the Limitations of Esophageal Robotic Surgery in Children.

INTRODUCTION: There have been numerous reports of robotic pediatric surgery in the literature, particularly regarding urological procedures for school-aged children. Thoracic procedures appear to be less common, despite the fact that encouraging results were reported more than 10 years. Our aim was to report a national experience of esophageal robotic-assisted thoracoscopic surgery (ERATS) and to discuss the most appropriate indications. MATERIALS AND METHODS: A retrospective multicenter study was conducted to compile the ERATS performed at five French surgical centers that have been involved in spearheading robotic pediatric surgery over the past 15 years. The data were supplemented by a review of the literature. RESULTS: Over the study period, 68 cases of robotic thoracic surgery were performed at the five pediatric centers in question. ERATS was performed for 18 patients (mean age 7.1 years [ ± 5.6]) in four of the centers. These comprised seven esophageal duplications, four esophageal atresias, five Heller's myotomies, and two cases of esophagoplasty. A conversion was needed for two neonates (11%) due to exposure difficulties. Four other procedures for patients who weighed less than 15 kg were successfully completed without causing postoperative complications. In the past 12 years, 22 other cases of ERATS were published worldwide. The indications were the same, except for esophagoplasty, which was not found. CONCLUSION: Aside from accessibility issues with the robotic platform, the main limitation is still very much that the low body weight of children results in incompatibility between the size of the trocars and the size of the intercostal space. ERATS is clearly a feasible procedure with technical advantages for most pediatric cases with body weights more than 15 kg. A transdiaphragmatic abdominal approach should be considered for lower esophagus surgery.

Comparison of the Learning Curve for Robot-Assisted Laparoscopic Pyeloplasty Between Senior and Junior Surgeons.

Introduction: The widespread use of robotic surgery has provided surgeons a high-quality and alternative method to perform pyeloplasty. Indeed, robot-assisted technology has made it a lot easier to obtain the advanced technical skills required to perform this procedure. The learning curve (LC) reflects the increase in learning as a function of experience. Robot-assisted laparoscopic pyeloplasty (RALP) represents a well-standardized and reproducible procedure with an LC that allows reliable results to readily be obtained. The aim of our study was to compare the RALP LC of senior versus junior surgeons. Materials and Methods: We reviewed all of the RALP procedures performed at three pediatric surgery centers between November 2007 and November 2018. Three senior surgeons and 4 junior surgeons performed the robotic procedures. Neither the senior nor the junior surgeons had previous experience with robotic surgery; they had experience with conventional laparoscopic procedures but not with laparoscopic pyeloplasty. The primary metric that we selected to evaluate competence acquisition was a composite outcome defined by a combination of operative time (OT), complications, and surgical success. The complications were rated according to the Clavien-Dindo classification expressed by a complication factor; surgical success was expressed as a success factor, and we used a cumulative sum (CUSUM) analysis to determine the LC. The CUSUM method, through its multioutcome approach, is a very effective way to evaluate LCs. Results: Between November 2007 and November 2018, 3 senior surgeons and 4 junior surgeons performed 88 RALP procedures. The included patients had a median age of 6.1 years (range 7 months-16 years). The median duration of follow-up was 6.4 years (range 14 months-12 years). The median OT was 198.86 minutes (range 106-335 minutes). By CUSUM analysis of the composite outcome, we found that despite the junior surgeons having performed fewer procedures than the senior surgeons, their LCs exhibited an earlier inflection point (Fig. 1) followed by a constant rate of improvement in proficiency, thus indicating a more rapid learning process. The median composite scores for the senior surgeons and the junior surgeons were 299 (range 210-370) and 193 (range 131-255), respectively, after seven procedures. Conclusion: Assuming proper exposure to robotics and an adequate case volume, we demonstrated that junior surgeons can readily achieve comparable levels of expertise compared with senior practitioners in the field of pediatric RALP. It can be assumed that the LC in robotic pyeloplasty is not only directly influenced by the individual surgical experience but also by the experience of the surgical team.

Outcomes of laparoscopic and open surgical treatment of intestinal malrotation in children.

BACKGROUND: The safety of the laparoscopic treatment of intestinal malrotation remains controversial. This study compared the outcomes of laparoscopic and open surgical treatment of intestinal malrotation. METHODS: A multicentric retrospective study included pediatric cases of intestinal malrotation operated on between 2005 and 2016. RESULTS: This study included 227 children with a median age of 17 days (0-17.2 years), including 161 with a midgut volvulus. Forty-six(20.3%) procedures were started by laparoscopy and 181(79.7%) by laparotomy. Laparoscopy was more frequent for elective surgery (45.9%) than for emergency procedures (10.8%, p < 0.001). Conversions were significantly more frequent during emergency procedures (66.7% vs 17.9%)(p = 0.001). Considering only 61 elective surgeries, the mean hospital stay was significantly shorter after laparoscopy (5.3 days +/-5.2 vs 10.1 days +/-13, p = 0.01), the overall complication rate was comparable (15.8% vs 21.7%, p = 0.7) but post-operative volvulus was significantly more frequent after laparoscopy (13% vs 0%, p = 0.04). Outcomes of the two approaches were not significantly different after 166 emergency procedures. CONCLUSION: Laparoscopy can be performed by experienced team for the treatment of selected cases of intestinal malrotation. Conversion to open surgery should be done with a low threshold, as the rate of volvulus recurrence is concerning. LEVEL OF EVIDENCE: Level III.

Relationships Between Managerial and Organizational Practices, Psychological Health at Work, and Quality of Care in Pediatric Oncology.

PURPOSE: Psychological health at work for care providers is an important issue, because they are directly involved in quality of patient care. Managerial and organizational determinants have been found to be indicators of psychological health at work. The main objective of this study was to explore the relationships between the psychological health at work of pediatric oncology care workers with managerial and organizational determinants and with quality of care. MATERIALS AND METHODS: We performed regression analysis between psychological health at work (quality of work life [QWL], job satisfaction, and so on), managerial determinants (transformational leadership, perceived autonomy support), organizational determinants (organizational support, organizational justice, and participatory approach), and perceived quality of care. RESULTS: Participants were 510 health care professionals working in French pediatric oncology centers. No significant differences in the psychological health at work of the participants were found based on age, sex, length of employment, or professional discipline. In simple regression, significant associations were found between psychological health at work with all managerial and organizational determinants. In multiple regression, a significant link was found between QWL and perceived organizational support (ß = .21; P < .001), organizational justice (ß = .20, P < .001), and overall participatory approach (ß = .10; P < .02). Job satisfaction was also related to perceived organizational support (ß = .16; P < .01). Finally, perceived quality of care was linked to QWL (ß = .15; P < .01) and job satisfaction (ß = .30; P < .001). CONCLUSION: These results emphasize the importance of the role of managers and the organization in psychological health at work of health care providers and also in the quality of patient care.

Bisphenol S Impaired Human Granulosa Cell Steroidogenesis in Vitro.

Bisphenol S (BPS) is a structural analog of the endocrine disruptor bisphenol A (BPA); it is the main BPA replacement in the plastics industry. Previous studies have shown that BPA and BPS exhibit similar effects on reproduction in fish and rodent species. BPS reportedly alters steroidogenesis in bovine granulosa cells. Luteinised granulosa cells collected from 59 women who were undergoing an in vitro fertilization procedure were cultured for 48 h in the presence or absence of BPS (10 nM, 100 nM, 1 µM, 10 µM or 50 µM). BPS exposure was investigated by assessing follicular fluids from these 59 women for their BPS content. Culture medium, cells, total messenger RNA (mRNA) and total protein extracted from the luteinised granulosa cells were examined for oestradiol and progesterone secretion, cellular proliferation, viability, gene expression, steroidogenic enzyme expression and cell signaling. BPS was measured in follicular fluids using mass spectrometry. Exposure of granulosa cells to 10 or 50 µM BPS for 48 h induced a 16% (p = 0.0059) and 64% (p < 0.0001) decrease, respectively, in progesterone secretion; 50 µM BPS decreased oestradiol secretion by 46% (p < 0.0001). Ten µM BPS also tended to reduce CYP11A1 protein expression by 37% (p = 0.0947) without affecting HSD3B1 and CYP19A1 expression. Fifty µM BPS increased ERRγ expression. Environmental levels of BPS (nanomolar range) did not induce changes in steroidogenesis in human granulosa cells. The effects of BPS were observed after only 48 h of BPS exposure. These acute effects might be similar to chronic effects of physiological BPS levels.

Bisphenol A and S impaired ovine granulosa cell steroidogenesis.

Bisphenols, plasticisers used in food containers, can transfer to food. Bisphenol A (BPA) has been described as an endocrine disruptor and consequently banned from the food industry in several countries. It was replaced by a structural analogue, Bisphenol S (BPS). BPA action on the steroidogenesis is one of the mechanisms underlying its adverse effects on the efficiency of female reproduction. This study aimed to determine whether BPS is a safe alternative to BPA regarding GC functions. Antral follicles (2-6 mm), of approximatively 1000 adult ewe ovaries, were aspired and GC purified. For 48 h, ovine GC were treated with BPA or BPS (from 1 nM to 200 µM) and the effects on cell viability, proliferation, steroid production, steroidogenic enzyme expression and signalling pathways were investigated. Dosages at and greater than 100 µM BPA and 10 µM BPS decreased progesterone secretion by 39% (P < 0.001) and 22% (P = 0.040), respectively. BPA and BPS 10 µM and previously mentioned concentrations increased oestradiol secretion two-fold (P < 0.001 and P = 0.082, respectively). Only 100 µM BPA induced a decrease (P < 0.001) in gene expression of the enzymes of steroidogenesis involved in the production of progesterone. BPA reduced MAPK3/1 phosphorylation and ESR1 and ESR2 gene expression, effects that were not observed with BPS. BPA and BPS altered steroidogenesis of ovine GC. Thus, BPS does not appear to be a safe alternative for BPA. Further investigations are required to elucidate BPA and BPS mechanisms of action.

Minimally invasive surgery for unilateral Wilms tumors: Multicenter retrospective analysis of 50 transperitoneal laparoscopic total nephrectomies.

PURPOSE: To evaluate feasibility and outcomes of minimally invasive surgery (MIS) in Wilms tumor (WT). METHODS: International multicenter review of MIS total nephrectomies for WT between 2006 and 2018. Medical records of confirmed WT were retrospectively assessed for demographic, imaging, treatment, pathology, and oncological outcome data. RESULTS: Fifty patients, with a median age of 38 months (6-181), were included in 10 centers. All patients received neoadjuvant chemotherapy, as per SIOP protocol. Median tumor volume post-chemotherapy was 673 mL (18-3331), 16 tumors crossed the lateral border of the spine, and three crossed the midline. Six patients with tumors that crossed the lateral border of the spine (tumor volumes 1560 mL [299-2480]) were converted to an open approach. There was no intraoperative tumor rupture. Overall, MIS was completed in 19% of the 195 nephrectomies for WT presenting during the study period. Tumor was stage I in 29, II in 16, and III in 5, and histology was reported as low in three, intermediate in 42, and high risk in five. Three patients had positive tumor margins. After a median follow-up of 34 months (2-138), there were two local recurrences (both stage I, intermediate risk, 7 and 9 months after surgery) and one metastatic relapse (stage III, high risk, four months after surgery). The three-year event-free survival was 94%. CONCLUSION: MIS is feasible in 20% of WT, with oncological outcomes comparable with open surgery, no intraoperative rupture, and a low rate of local relapse. Ongoing surveillance is, however, needed to evaluate this technique as it becomes widespread.

Bisphenol S Impaired In Vitro Ovine Early Developmental Oocyte Competence.

INTRODUCTION: Bisphenol A (BPA) is a widespread compound in the plastic industry that is especially used to produce baby bottles, food packaging and metal cans. BPA, an endocrine disruptor, leads to alterations in reproductive function and therefore has been banned from the food industry. Unregulated BPA analogues, particularly Bisphenol S (BPS), have emerged and are now used in the plastic industry. Thus, this study aimed to examine the acute effects of low and environmental doses of BPS on ewe oocyte quality and developmental competence, and its mechanism of action, during in vitro maturation. METHODS: Ewe cumulus-oocyte complexes underwent in vitro maturation in the presence or absence of BPS (1 nM, 10 nM, 100 nM, 1 µM or 10 µM). Oocytes were then subjected to in vitro fertilisation and development. RESULTS: 1 µM BPS induced a 12.7% decrease in the cleavage rate (p = 0.004) and a 42.6% decrease in the blastocyst rate (p = 0.017) compared to control. The blastocyst rate reduction was also observed with 10 nM BPS. Furthermore, 10 µM BPS reduced the oocyte maturation rate, and 1 µM BPS decreased cumulus cell progesterone secretion. PR and AMH gene expression were reduced in cumulus cells. BPS induced a 5-fold increase in MAPK 3/1 activation (p = 0.04). CONCLUSIONS: BPS impaired ewe oocyte developmental competence. The data suggest that BPS might not be a safe BPA analogue. Further studies are required to elucidate its detailed mechanism of action.