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All 17 supplementary figures and legends in a pdf file

Pediatric liver cancers (PLC) comprise diverse diseases affecting infants, children, and adolescents. Despite overall good prognosis, PLCs display heterogeneous response to chemotherapy. Integrated genomic analysis of 126 pediatric liver tumors showed a continuum of driver mechanisms associated with patient age, including new targetable oncogenes. In 10% of patients with hepatoblastoma, all before three years old, we identified a mosaic premalignant clonal expansion of cells altered at the 11p15.5 locus. Analysis of spatial and longitudinal heterogeneity revealed an important plasticity between “hepatocytic,” “liver progenitor,” and “mesenchymal” molecular subgroups of hepatoblastoma. We showed that during chemotherapy, “liver progenitor” cells accumulated massive loads of cisplatin-induced mutations with a specific mutational signature, leading to the development of heavily mutated relapses and metastases. Drug screening in PLC cell lines identified promising targets for cisplatin-resistant progenitor cells, validated in mouse xenograft experiments. These data provide new insights into cisplatin resistance mechanisms in PLC and suggest alternative therapies.Significance:PLCs are deadly when they resist chemotherapy, with limited alternative treatment options. Using a multiomics approach, we identified PLC driver genes and the cellular phenotype at the origin of cisplatin resistance. We validated new treatments targeting these molecular features in cell lines and xenografts.This article is highlighted in the In This Issue feature, p. 2355

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Background Early biliary drainage surgery (BDS; Kasai) is associated with longer transplant-free survival in biliary atresia. However, evidence is lacking on whether an age limit can be established at which liver transplantation should be performed as first-line treatment for children with a delayed diagnosis of biliary atresia. The aim of the current study was to compare the outcome of a large cohort of children with biliary atresia who underwent BDS after 90 days of life with those who underwent early BDS (before 90 days) and those who did not receive BDS and were directly referred for primary liver transplantation. Methods All patients with biliary atresia treated at Bicêtre, Paris-Saclay University Hospital between 1995 and 2017 were analysed in this STROBE-compliant study. Three groups were defined: BDS before 90 days of life (early BDS); BDS after 90 days of life (late BDS); and patients without BDS who were referred for primary liver transplantation (no BDS). Patient characteristics, overall survival, and native liver survival were compared. Results Of 424 children with biliary atresia, 69 patients (16 per cent) were older than 90 days when they underwent BDS. Twenty-five patients had no BDS and were referred for primary liver transplantation (6 per cent). The main reason for not performing BDS was manifest portal hypertension (18/25). Two- and 5-year transplant-free survival were significantly higher in patients with late BDS compared with no BDS (53.5 versus 12.0 per cent respectively for 2-year data and 30.4 versus 4.0 per cent respectively for 5-year data, P < 0.001). Five- and 10-year overall survival did not differ between early BDS (92 and 91 per cent respectively), late BDS (88 and 83 per cent respectively) and no BDS (80 and 80 per cent respectively, P = 0.061). Conclusion Age alone should not routinely be considered a contraindication to BDS in patients older than 90 days. Liver transplantation in infancy (less than 12 months) could be avoided in 88 per cent of cases with late diagnosis of biliary atresia and is delayed significantly even when BDS is performed after 3 months. Overall survival is at least equal to patients who are referred for primary liver transplantation.

International audience; No abstract available

Objective: To evaluate the educational impact of a pilot MOOC (Massive Open Online Course), validated by the French College of Urology Teachers (FCUT), on the surgical technique of kidney transplantation.Materials and methods: We developed a MOOC on the surgical technique of kidney transplantation, based on a video of a surgical procedure, performed by an expert surgeon. The MOOC has been validated by the FCUT. We have created 2 student groups: 1) MOOC-pre-QCM group: visualization of the MOOC then answer to the MCQs and satisfaction questions; 2) MOOC-post-QCM group: answer to the MCQs then visualization of the MOOC then answers to the satisfaction questions. In total, 20 MCQs on the kidney transplantation technique were completed by the 2 groups. The answers were anonymous.Results: A total of 142 people answered the MCQs (MOOC-pre-QCM group (n=66) and MOOC-post-QCM group (n=76)). Twenty-nine percent (41/142) of the participants were fellows and 71 % (101/142) were residents. The proportion of fellows and residents was identical between the 2 groups. The rate of correct answers to the 20 MCQs was statistically higher in the MOOC-pre-QCM group, compared to the MOOC-post-QCM group (88.6 % versus 73.3 %, P, ObjectifÉvaluer l’impact pédagogique d’un MOOC (Massive Open Online Course) pilote, validé par le Collège français des enseignants en urologie (CFEU), sur la technique chirurgicale de transplantation rénale.Matériel et méthodesNous avons réalisé un MOOC sur la technique chirurgicale de transplantation rénale, à partir d’une vidéo d’une intervention chirurgicale, réalisée par un chirurgien expert. Le MOOC a été validé par le CFEU. Nous avons créé 2 groupes d’étudiants : 1) groupe MOOC-pré-QCM : visualisation du MOOC, puis réponse aux QCM et aux questions de satisfaction ; 2) groupe MOOC-post-QCM : réponse aux QCM, puis visualisation du MOOC, puis réponse aux questions de satisfaction. Au total, 20 QCM sur la technique transplantation rénale ont été remplis par les 2 groupes. Les réponses étaient anonymes.RésultatsAu total, 142 personnes ont répondu aux QCM (groupe MOOC-pré-QCM (n = 66) et groupe MOOC-post-QCM (n = 76)). 29 % (41/142) des participants étaient des CCA ou assistants et 71 % (101/142) étaient des internes. La proportion de CCA/assistants et d’internes était identique entre les 2 groupes. Le taux de réponses correctes aux 20 QCM était statistiquement supérieur dans le groupe MOOC-pré-QCM, en comparaison au groupe MOOC post-QCM (88,6 % contre 73,3 %, p < 0,0001). Au total, 91 % des étudiants ont trouvé le MOOC « Très Utile » ou « Utile ». La médiane de la note du MOOC, donnée par les étudiants, était de 8/10.ConclusionCette étude a montré un impact positif du MOOC sur les connaissances théoriques de la technique chirurgicale de transplantation rénale. Ce MOOC pourrait servir de projet pilote pour le développement d’autres MOOC sur la chirurgie urologique.Niveau3.

Background : The true incidence and natural history of renal artery aneurysm (RAA) remain unclear and still exists controversy over indication for treatment. Several techniques of conventional surgical reconstructions are described in literature, and more recently endovascular therapies have been reported with satisfying results and lower complication rate. This paper aims to investigate the outcomes of both endovascular and open repair of RAA achieved in a single institution involving 3 medical teams (urology, vascular surgery and neuroradiology). Material and Methods : We conducted a single-centre retrospective observational study about all patients surgically or endovascularly treated for RAA over a 15-year period. Pre-operative, procedural and post-operative data at the early, mid- and long-term follow-up were collected and analysed, focusing on operative technique used for repair and related outcomes. Results : A total of 27 patients (n = 17 (63%) women, mean age 58 ± 13.2, n = 26 saccular RAA) were included. Mean aneurysm was size was 18.8 ± 6.3 mm. Most diagnosis were accidental. Symptomatic RAA showed with macroscopic haematuria (n = 3, 25.9%), unstable hypertension (n = 2; 7%), chronic lumbar pain (n = 1, 3.7%) and renal infarct (n = 1, 3.7%). Conventional surgery (ex-vivo repair, aneurysmorraphy, aneurysm resection and end-to-end anastomosis) was performed in 14 (51.8%) cases and endovascular coiling embolization in 13 (48.2%). Mean hospital length of stay was 5.4 ± 3.6 days. Intensive Care Unit stay was needed only in the surgically treated patients (mean 1.1 ± 1.2 days). During the early follow-up, morbidity rate was 7/14 in surgically treated patients vs. 1/13 in endovascular group; it included bleeding, retroperitoneal hematoma, arterial thrombosis and bowel obstruction. The discharge imaging showed complete aneurysm exclusion and renal artery patency in all cases. At a mean follow-up of 39 ± 42 months, 3 patients (11%) were lost to follow up and 2 (7.4 %) died from unrelated cause. None of these patients required dialysis but a statistically significant (P = 0.09) decrease in GFR was noted between the preoperative period and last follow-up control. RAA repair neither showed blood pressure control improvement nor reduced the need for anti-hypertensive drug use. Conclusion : Open or endovascular techniques are both safe and efficient to treat RAA. Even though, surgical management is burdened with higher morbidity rate, the operative technique should be selected according to anatomical features, diameters and location of RRA; and the number of renal branches involved. Further larger studies are needed to define the feasibility and safety for a wider application of the endovascular approach.

Additional file 1: Additional Table 1. Teams conducting the PrevHPV program (The PrevHPV Consortium). Additional Table 2. COREQ (COnsolidated criteria for REporting Qualitative research) Checklist. Additional Table 3. STROBE (STrengthening the Reporting of OBservational studies in Epidemiology) Statement — checklist of items that should be included in reports of observational studies. Additional Table 4. Characteristics of the middle schools invited to participate in the study and of those which accepted to participate. Additional Table 5. Additional illustrative verbatim of participants to the focus groups. Additional Table 6. Psychological antecedents of vaccination (5C scale) among participants to the self-administered online questionnaire and by profession. Additional Table 7. Public health topics discussed with pupils by participants to the self-administered online questionnaire and by profession. Additional Table 8. Appropriate period to propose HPV vaccination among pupils according to participants to the self-administered online questionnaire and by profession. Additional Document 1. Self-administered online questionnaire. Additional Document 2. Focus groups’ interview guide. Additional Document 3. Names of the PrevHPV Study Group’s members.