Search

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. This was a prospective analysis performed over a period of 4 years. Treatment was delivered according to the Societe Internationale d’Oncologie Pediatrique/International Society of Paediatric Oncology Europe Neuroblastoma Group (SIOP/SIOPEN) protocols. Indications were approved by a certified tumor board. 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. 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.

Laparoscopic Nissen fundoplication (LNF) and gastrostomy tube (GT) placement may be performed concomitantly in children with gastro-esophageal reflux disease (GERD) and failure to thrive. We aimed to evaluate the rate and risk factors for LNF failure in children undergoing concomitant LNF/GT. A retrospective multi-institutional cohort study was conducted, reviewing patients that underwent LNF (2005–2014). Data collected included patient demographics, comorbidities, and type of GT (laparoscopy- or endoscopy-assisted). The primary outcome measure was LNF failure. Data was compared using contingency tables or Mann–Whitney tests, when appropriate. An exploratory analysis by Kaplan–Meier survival and Cox proportional hazards analysis was performed to determine predictors of time to LNF failure after LNF/GT. Of 189 children that underwent LNF, 99 (52%) had a concomitant GT (55% laparoscopy-, 45% endoscopy-assisted). LNF failed in 15% after LNF/GT and in 17% after LNF alone (p = 0.84), at a median age of 23 months (IQR 8–41). Using univariate analysis, we found that a younger age at the time of surgery (p = 0.05), prematurity (p = 0.0018), esophageal atresia (p = 0.01), and endoscopy-assisted GT (p = 0.02) were potential predictors of LNF failure after LNF/GT. After multivariate regression analysis, prematurity (p = 0.007) remained significantly associated with LNF failure after LNF/GT. No predictive factors for LNF failure after LNF alone were identified. Concomitant GT insertion and LNF is a common practice, as half of the children that undergo LNF also received GT insertion. Children born preterm or with esophageal atresia comprise a fragile population at high-risk of LNF failure after LNF/GT. Prospective, multicentric studies are needed to evaluate the best GT technique to use in children undergoing LNF.

A series of 6-polyaminosteroid analogues of squalamine were synthesized with moderate to good yields and evaluated for their in vitro antimicrobial properties against both susceptible and resistant Gram-positive (vancomycin-resistant Enterococcus faecium and methicillin-resistant Staphylococcus aureus) and Gram-negative (carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa) bacterial strains. Minimum inhibitory concentrations against Gram-positive bacteria ranged from 4 to 16 µg/mL for the most effective compounds, 4k and 4n, and showed an additive or synergistic effect with vancomycin or oxacillin. On the other hand, the derivative 4f, which carries a spermine moiety like that of the natural trodusquemine molecule, was found to be the most active derivative against all the resistant Gram-negative bacteria tested, with an MIC value of 16 µg/mL. Our results suggest that 6-polyaminosteroid analogues of squalamine are interesting candidates for Gram-positive bacterial infection treatments, as well as potent adjuvants to fight Gram-negative bacterial resistance.

The control of mRNA turnover is essential in bacteria to allow rapid adaptation, especially in opportunistic pathogen like Enterococcus faecalis. This mechanism involves RNase and DEAD-box helicases that are key elements in RNA processing and their associations form the degradosome with accessory proteins. In this study, we investigated the function of four RNases (J1, J2, Y and III) and three DEAD-box helicases (CshA, CshB, CshC) present in most Enterococci. The interactions of all these RNA metabolism actors were investigated in vitro, and the results are in accordance with a degradosome structure close to the one of Bacillus subtilis. At the physiological level, we showed that RNase J1 is essential, whereas RNases J2 and III have a role in cold, oxidative and bile salts stress response, and RNase Y in general fitness. Furthermore, RNases J2, Y and III mutants are affected in virulence in the Galleria mellonella infection model. Concerning DEAD-box helicases, all of them are involved in cold shock response. Since the ΔcshA mutant was the most stress impacted strain, we studied this DEAD-box helicase CshA in more detail. This showed that CshA autoregulates its own expression by binding to its mRNA 5'Unstranslated Region. Interestingly, CshC is also involved in the expression control of CshA by a hitherto unprecedented mechanism.

Retrocaval ureter (RCU) is a rare congenital anomaly and published data on pediatric laparoscopic management are poor. The aim of this study was to report our experience of retroperitoneal laparoscopic approach for management of RCU in children. A retrospective review of data from patients treated for RCU between 2002 and 2018 in our institution was performed. All patients were positioned in a flank position and underwent a three-port (5-mm optical trocar and two 3-mm trocars) laparoscopic retroperitoneal ureteroureterostomy. Anastomosis was made by 6/0 absorbable sutures. A JJ stent was always inserted. Five patients with a median age of 94 months (5–152) were operated on and followed up for a median time of 103 months (46–201). Median operating time was 200 min (160–270). No conversion and no transfusion occurred. Median hospital stay was 2 days (1–4). Ureteral stent was removed after 52 days (47–82). Complications included pyelonephretis (N = 1). In all cases, hydronephrosis decreased postoperatively. Retroperitoneal laparoscopic approach for RCU is safe and effective in children. Our video demonstrates different patients with specific surgical details to show how to manage these children. The global vision of the upper tract by laparoscopy leads to optimal management of these children even if the anomaly was not detected preoperatively.

Background: The use of robotics has become commonplace in adult oncology but remains rare in paediatric oncologic surgery. We present the results of a large nationwide experience with robotic surgery in children with benign and malignant tumours. Methods: Prospective analysis (ClinicalTrials.gov NCT03274050) of robotic procedures performed between 2008 and 2019. Children received treatment according to the ongoing SIOP/SIOPEN protocols. Indications were approved by a certified tumour board. Findings: A total of 100 tumours were resected during 92 procedures in 87 children (56 girls). The median age at surgery was 7·4 years (3·5-12); 20% of children harboured germinal genetic alterations predisposing to cancer. Procedures were performed by laparoscopy for abdominal (71%) or pelvic tumours (10%) and by retroperitoneoscopy (5%) or thoracoscopy (14%). No intraoperative tumour rupture occurred during robotic-assisted dissection. Eight conversions (9%) to an open approach occurred. Neuroblastic tumour (n=29) was the main group (19 neuroblastomas, three ganglioneuroblastomas, seven ganglioneuromas). Renal tumour was the second largest group (n=24, including 20 Wilms’ tumours). The other 47 tumours were neuroendocrine (n=13), adrenal (n=11), pancreatic (n=3), germ-cell (n=7), thymic (n=4), inflammatory myofibroblastic (n=4) and five different rare tumours. Overall, 50 tumours were malignant, 2 were borderline and 48 were benign. The median hospital stay was 3 days (2-4). Five post-operative surgical complications occurred within the first 30 days in four patients. During a follow-up of 1 to 28 months, one child (Wilms’ tumour) presented pleural recurrence. One girl with Wilms’ tumour died of central nervous system metastasis. Interpretation: Robotic surgery for paediatric tumours is feasible and may be an option in highly selected cases. Indications should be discussed by tumour boards to avoid widespread and uncontrolled application of the approach. Children with genetic predisposition to cancer seem good candidates for the robotic approach. Trial Registration: ClinicalTrials.gov NCT03274050 Funding: The sponsor was Assistance Publique–Hopitaux de Paris (APHP, Clinical Research and Innovation Delegation) and this project was funded by a grant from Necker Hospital. Declaration of Interests: None to declare. Ethics Approval Statement: This prospective analysis received approval from institutional review boards and an independent ethics committee (Comite de Protection des Personnes, CPP Ile de France VII). The sponsor was Assistance Publique–Hopitaux de Paris (APHP, Clinical Research and Innovation Delegation).

In Hirschsprung’s disease (HSCR), postoperative course remains unpredictable. Our aim was to define predictive factors of the main postoperative complications: obstructive symptoms (OS) and Hirschsprung-associated enterocolitis (HAEC). In this prospective multicentre cohort study, samples of resected bowel were collected at time of surgery in 18 neonates with short-segment HSCR in tertiary care hospitals. OS and HAEC were noted during postoperative follow-up. We assessed the enteric nervous system and the intestinal epithelial barrier (IEB) in ganglionic segments by combining immunohistochemical, proteomic and transcriptomic approaches, with functional ex vivo analysis of motility and para/transcellular permeability. Ten HSCR patients presented postoperative complications (median follow-up 23.5 months): 6 OS, 4 HAEC (2 with OS), 2 diarrhoea (without OS/HAEC). Immunohistochemical analysis showed a significant 41% and 60% decrease in median number of nNOS-IR myenteric neurons per ganglion in HSCR with OS as compared to HSCR with HAEC/diarrhoea (without OS) and HSCR without complications (p = 0.0095; p = 0.002, respectively). Paracellular and transcellular permeability was significantly increased in HSCR with HAEC as compared to HSCR with OS/diarrhoea without HAEC (p = 0.016; p = 0.009) and HSCR without complications (p = 0.029; p = 0.017). This pilot study supports the hypothesis that modulating neuronal phenotype and enhancing IEB permeability may treat or prevent postoperative complications in HSCR.

Enterococcus faecalis is an opportunistic multidrug-resistant human pathogen causing severe nosocomial infections. Previous investigations revealed that the CroRS two-component regulatory pathway likely displays a pleiotropic role in E. faecalis, involved in virulence, macrophage survival, oxidative stress response as well as antibiotic resistance. Therefore, CroRS represents an attractive potential new target for antibiotherapy. In this report, we further explored CroRS cellular functions by characterizing the CroR regulon: the 'domain swapping' method was applied and a CroR chimera protein was generated by fusing the receiver domain from NisR to the output domain from CroR. After demonstrating that the chimera CroR complements a croR gene deletion in E. faecalis (stress response, virulence), we conducted a global gene expression analysis using RNA-Seq and identified 50 potential CroR targets involved in multiple cellular functions such as cell envelope homeostasis, substrate transport, cell metabolism, gene expression regulation, stress response, virulence and antibiotic resistance. For validation, CroR direct binding to several candidate targets was demonstrated by EMSA. Further, this work identified alr, the gene encoding the alanine racemase enzyme involved in E. faecalis resistance to D-cycloserine, a promising antimicrobial drug to treat enterococcal infections, as a member of the CroR regulon.

We have studied outcome of double-face preputial island flap (DFPIF) technique in severe types of hypospadias: penoscrotal, scrotal and perineal. We have used DFPIF in 75 boys at a median age of 1.1 years (1.0–1.5). The meatus was penoscrotal, scrotal or perineal after de-gloving the penis. The inner face of the foreskin was used for urethroplasty and the outer face for ventral skin covering. Modifications were added: proximal anastomosis was protected by a spongioplasty; in case of urethral plate transection, we anastomosed on onlay proximal and distal segments of the flap (onlay-tube-onlay) and the tubularized part was sutured to corpus cavernosa. FU was scheduled at one month then every 3 months for a year then annually. At each consultation, the surgeon filled out a detailed cosmetic and functional sheet including flowmeter. Thirty-four patients had onlay preputial flap repair with urethral plate preservation. Forty-one had the onlay-tube-onlay technique. All children had a curvature, 19 had a significant residual curvature after dissection, corrected by dorsal plication (n = 9) and ventral lengthening (n = 10). Median FU was 4.2 years (2.7–6.5). 36 children (48%) had complications and needed redo surgery: 12 fistulas, 11 diverticula, 7 meatal stenosis, 3 strictures and 2 residual curvatures. All children but three voided within the normal limits for their age. DFPIF remains a good option for a one-stage repair of severe hypospadias. After a median of 1.8 procedures, the final success rate was 96%. The healthy well-vascularized ventral skin allows safe redo surgery when needed.

The control of mRNA turnover is essential in bacteria to allow rapid adaptation, especially in opportunistic pathogen like Enterococcus faecalis. This mechanism involves RNase and DEAD-box helicases that are key elements in RNA processing and their associations form the degradosome with accessory proteins. In this study, we investigated the function of four RNases (J1, J2, Y and III) and three DEAD-box helicases (CshA, CshB, CshC) present in most Enterococci. The interactions of all these RNA metabolism actors were investigated in vitro, and the results are in accordance with a degradosome structure close to the one of Bacillus subtilis. At the physiological level, we showed that RNase J1 is essential, whereas RNases J2 and III have a role in cold, oxidative and bile salts stress response, and RNase Y in general fitness. Furthermore, RNases J2, Y and III mutants are affected in virulence in the Galleria mellonella infection model. Concerning DEAD-box helicases, all of them are involved in cold shock response. Since the ΔcshA mutant was the most stress impacted strain, we studied this DEAD-box helicase CshA in more detail. This showed that CshA autoregulates its own expression by binding to its mRNA 5ʹUnstranslated Region. Interestingly, CshC is also involved in the expression control of CshA by a hitherto unprecedented mechanism.

International audience; Enterococcus faecalis has to cope with major stress conditions during colonization. To understand the effects of stress encountered during infection, the present study assessed the transcriptomic response of the bacteria facing exposure to serum, urine, bile salts, acid pH, or oxidative stress. Compared to non-stressed culture, 30% of the E. faecalis genes were differentially expressed. The transcriptome analysis reveals common but also specific responses, depending on stresses encountered: thus, urine exposure has the most important impact, and the highest number of genes with modified expression is involved in transport and metabolism. The results also pinpoint many stress-related sRNA or intergenic regions not yet characterized. This study identified the general stress stimulon related to infection: when the commensal bacterium initiates its response to stress related to infection, it increases its ability to survive to rough conditions for colonization, rather than promoting expression of virulence factors, and becomes this opportunistic pathogen that thrives in hospital settings.

Objective: To show the interest of tractography in pelvic surgery by a demonstrative case of neurofibroma resected by robotic assisted laparoscopy. Summary background data: Although diffusion tensor magnetic resonance imaging, along with tractography algorithms, is increasingly included in image guided neurosurgery methods, it is less frequently used for the peripheral nervous system such as the pelvic sacral plexus. We report one observation demonstrating the interest of such image data for pelvic surgery. Methods: A 12-years-old girl with neurofibromatosis presented with a growing left pelvic neurofibroma on repeated pelvic MRI with an increased SUV (2.83) on PET scan. A diffusion tensor pelvic MRI was performed before and after robotically assisted tumoral resection, and a tractography algorithm was applied on both images. Results: The pre-operative tractogram showed the nervous nature of the tumor in close contact with the left sacral plexus. Section of a nerve trunk encased in the neurofibroma was mandatory for the resection and well documented by the 3D enhanced vision provided by the robot. Post-operatively, the patient showed a slight paresthesia and dysesthesia of the left leg calf and of the plantar vault (left S2 territory), without any motor deficit. The post-operative tractogram showed a thinning of the left S2 sacral root and the disappearance of right aberrant nervous tracts. Conclusions: This clinical case validates the ability of pelvic tractography to deliver a proper imaging of the sacral nervous network and emphasizes the potential usefulness of this approach in pelvic surgery management, with perspectives of image-guided surgery. Keywords: NF1, Tractography, MRI, Robotic pelvic surgery

Aim We present the preliminary results of robotic-assisted laparoscopic (RAL) total and partial nephrectomy for renal malignant tumors in children. Methods This is a prospective study of patients operated with RAL between December 2016 and September 2018. Patients with Wilms tumors were treated according to the SIOP-2001 protocol. Patient and tumor characteristics, type of surgery, surgical-related morbidity, and oncologic outcomes were recorded. Results were compared with a series of patients with similar age- and tumor-related characteristics operated during the same period by an open surgical approach. Results Ten children underwent RAL nephrectomy with a mean age of five years (3.2-14.1 years). Total nephrectomy was done in six cases for Wilms tumor and in one case for renal sarcoma; three cases were converted. Complete removal of tumor without rupture was achieved in all cases. Postoperative course was uneventful, and patients were discharged between days 2 and 7. Neither recurrence nor medium-term complications occurred. Nine patients are alive with a median follow-up of 16 months (6-27 months) and one female died from complications of central nervous system metastases one year after surgery. When compared with the open surgical approach group, median tumor volume was smaller (P = 0.005), hospital stay was shorter (P = 0.01), and operative time was similar (P = 0.20). Conclusions RAL total and partial nephrectomy procedure for renal tumor in children may be an option in carefully selected cases. Indication should be discussed at tumor boards and surgery performed while adhering strictly to oncological surgical rules.

Lactic acid bacteria (LAB) strains OB14 and OB15 were isolated from traditional Tunisian fermented dairy products, Testouri cheese and Rigouta, respectively. They were identified as Enterococcus faecalis by the MALDI TOF-MS (matrix assisted laser desorption-ionization time of flight mass spectrometry) biotyper system and molecular assays (species-specific PCR). These new isolates were evaluated for probiotic properties, compared to E. faecalis Symbioflor 1 clone DSM 16431, as reference. The bacteria were found to be tolerant to the harsh conditions of the gastrointestinal tract (acidity and bile salt). They were low to moderate biofilm producers, can adhere to Caco-2/TC7 intestinal cells and strengthen the intestinal barrier through the increase of the transepithelial electrical resistance (TER). Susceptibility to ampicillin, vancomycin, gentamicin and erythromycin has been tested using the broth microdilutions method. The results demonstrated that E. faecalis OB14 and OB15 were sensitive to the clinically important ampicillin (MIC = 1 μg/mL) and vancomycin (MIC = 2 μg/mL) antibiotics. However, Whole Genome Sequencing (WGS) showed the presence of tetracycline resistance and cytolysin genes in E. faecalis OB14, and this led to high mortality of Galleria Mellonella larvae in the virulence test. Hierarchical cluster analysis by MALDI TOF-MS biotyper showed that E. faecalis OB15 was closely related to the E. faecalis Symbioflor 1 probiotic strain than to OB14, and this has been confirmed by WGS using the average nucleotide identity (ANI) and Genome-to-Genome Hybridization similarity methods. According to these results, E. faecalis OB15 seems to be reliable for future development as probiotic, in food or feed industry.

The aim of our study was to report our experience in extended Hirschsprung's disease (HD) in children operated on by laparoscopy.Retrospective data collection from a single center from 1991 to 2013 concerned extended forms of HD operated on by laparoscopic Duhamel procedure and included extension of aganglionosis, comorbidities, short and late postoperative outcome, and results of endoscopy when performed.Thirty patients presented an extended form of aganglionosis: 5 involving the transverse colon, 10 the right colon, and 15 the ileum (median length = 15 cm, range 1-60). Short-term outcome showed 13% postoperative complications requiring redo-surgery: occlusion (n = 2), wall abscess (n = 1), and anastomotic leak (n = 1). Median follow-up was of 5 years (range: 1-19 years). Satisfying bowel control was reached in 53%, and 46% had a weight-for-age reference curve up to -1 SD. They had four stools per day on average, 13% of soiling, 6% of constipation, and 26% of recurrent abdominal distention. Late enterocolitis occurred in 22% (n = 7): 6 with ileum involvement and 1 extended to the transverse colon. Endoscopy showed Crohn-like ulcerations in 100% of these cases.Laparoscopic Duhamel procedure is a safe and effective surgical technique in the management of extended forms of HD, with a low postoperative morbidity, but the frequent occurrence of late enterocolitis associated with Crohn-like ulcerations impairs the late outcome. Link between HD and Crohn disease still requires to be investigated.

Although primary tracheobronchial tumors are extremely rare in children, recurrent respiratory symptoms resistant to conventional therapy require further investigations to exclude possible malignant obstructive causes. As the matter of fact, early diagnosis may allow minimally invasive surgeries, improving the standard of living and the globally survival rate. The aim of this article is to provide an overview of diagnosis and management of tracheobronchial tumors in the early age, since only few reports are reported in the worldwide literature.

Background: People engage in health information-seeking online when experiencing unusual or unfamiliar bodily changes. It is not well understood how people consult the Internet for health information after the onset of unfamiliar symptoms and before receiving a potential diagnosis, and how online information-seeking can help people appraise their symptoms. This lack of evidence may be partly due to methodological limitations in capturing in real time the online information-seeking process. Objective: We explored women’s symptom attribution and online health information-seeking in response to a hypothetical and unfamiliar breast change suggestive of cancer (nipple rash). We also aimed to establish the feasibility of capturing in real time the online information-seeking process with a tool designed to track participants’ online searches and visited websites, the VIZZATATM browser tracker. Methods: An online survey was completed by 56 cancer-free women (Mage = 60.34 years, SD = 7.73 years) responding to a scenario asking them to imagine noticing a red scaly rash on the nipple. Participants were asked to make symptom attributions when presented with the scenario (Time1) and again after seeking information online (Time2). The online tracking tool, embedded in the survey, was used to capture in real time participants’ search terms and accessed websites. Results: The tracking tool captured the search terms and accessed websites of most of the participants (46/56, 82%). For the rest (n=10, 18%), there was evidence of engagement in online information-seeking, e.g. medical terminology and cancer attribution at Time2, despite their searching activity not being recorded. Twenty five participants considered cancer as a potential cause for the nipple rash at Time1, yet only one of these used ‘cancer’ as a search term. Most participants (n=40, 87%) used rash-related search terms, particularly ‘nipple rash’ and ‘rash on nipple’. The majority (41/46, 89%) accessed websites containing breast cancer information, with the NHS webpage “Paget’s disease of the nipple” being the most visited one. At Time2, after engaging in the Internet search task, more participants attributed the nipple rash to breast cancer than at Time1, n=37 (66.1%) vs. n=25 (44.6%), although a small number of participants (n=6) changed from making a cancer attribution at Time1 to a non-cancer one at Time2. Conclusions: Making a cancer attribution for an unfamiliar breast change did not necessarily translate into cancer-termed searches. Equally, not all Internet searches led to a cancer attribution. The findings suggest that online information-seeking may not necessarily help women who experience unfamiliar breast cancer symptoms understand their condition. Despite some technical issues, this study showed that it is feasible to use an online browser tracking tool to capture in real time information-seeking about unfamiliar symptoms. ClinicalTrial: N/A

International audience; Background: Patient specific 3D modeling is the first step towards image-guidedsurgery, the actual revolution in surgical care. Pediatric and adolescent patients withrare tumors and malformations should highly benefit from these latest technologicalinnovations, allowing personalized tailored surgery. This study focused on the pelvicregion, located at the crossroads of the urinary, digestive and genital channels withimportant vascular and nervous structures. The aim of this study was to evaluate theperformances of different software tools to obtain patient specific 3D models, throughsegmentation of magnetic resonance images (MRI), the reference for pediatric pelvisexamination.Methods: Twelve software tools freely available on the Internet and two commercialsoftware tools were evaluated using T2-w MRI and diffusion- weighted MRI images.The software tools were rated accordingly to eight criteria, evaluated by three differentusers: automatization degree, segmentation time, usability, 3D visualization, presenceof image registration tools, tractography tools, supported OS, and potential extension(i.e. plugins).Results: A ranking of software tools for 3D modeling of MRI medical images, accordingto the set of predefined criteria, was given. This ranking allowed us to elaborateguidelines for the choice of software tools for pelvic surgical planning in pediatricpatients. The best-ranked software tools were Myrian Studio, ITK-SNAP and 3D Slicer,the latter being especially appropriate if nerve fibers should be included in the 3Dpatient model.Conclusion: This study proposed a comprehensive review of software tools for 3Dmodeling of the pelvis according to a set of eight criteria, and delivered specificconclusions for pediatric and adolescent patients that can be directly applied to clinicalpractice.

The aim of this study is to compare free-breathing routine multi detector computed tomography (MDCT) and laryngo-tracheal (LT) flexible endoscopy in the evaluation of tracheal impairment in children with vascular ring (VR). We performed a retrospective and monocentric study of all patients with VR from 1997 to 2014. Clinical data included: initial symptoms, type of surgery and clinical outcome. MDCT were blindly reviewed by two radiologists in consensus, independently of LT endoscopy results. Radiologic and endoscopic results were reviewed according to four criteria: percentage of tracheal narrowing, distance of the compression from carina, presence of bronchial compression and signs of tracheomalacia (TM). Concordance was evaluated for each criterion with a Spearman coefficient. From 1997 to 2016, 21 patients with a vascular ring were operated on, among which 57% by thoracoscopy: double aortic arch (n = 14), Neuhauser anomaly (n = 4) and Right aorta + aberrant right subclavian artery (n = 3). 90% of them presented with respiratory symptoms among which 43% of stridor. Chest X-ray was suggestive of VR in 87% of the cases. MDCT images and LT endoscopy results were available and analyzed for nine patients. Concordance (Spearman correlation coefficient) was excellent for percentage and level of tracheal narrowing (1) and good for TM (0.79). Free breathing routine MDCT is a reliable exam compared to LT endoscopy in the evaluation of tracheal impairment in children with VR. In case of respiratory symptoms (except stridor) and suggestive chest X-ray of VR, endoscopy could be avoided and routine MDCT alone performed.

The aim of our study was to report our experience in thoracoscopy in infants and neonates for vascular surgical conditions in neonates and infants and to compare our results to open surgery regarding the short-term outcome.We retrospectively reviewed all the patients operated in a single institution from 1997 to 2016 for persistent ductus arteriosus (PDA) and vascular ring (VR) anomalies. We compared our thoracoscopic series to a historical control group operated by open surgery. Data collection from charts and office notes included age and weight at surgery, cardiac ultrasound data for PDA, preoperative clinical symptoms for VR, type of surgery, operating time, analgesic treatment requirements, ventilation status during postoperative course, and early complications.The thoracoscopic group included 13 PDA (median age and weight at surgery: 34 days and 1800 g) and 11 VR (median age and weight at surgery: 8 months and 7000 g). The thoracoscopic group did not differ in preoperative symptoms and work-up, operating time, ventilation status, length of hospital-stay, and postoperative complications with the group operated on by thoracotomy, for either PDA or VR.Our short-term results in thoracoscopic PDA closure and VR anomalies surgery in neonates and infants are comparable to open surgery. Thoracoscopy seems to provide less pain especially for neonates and premature babies and allows to decrease the risk for postoperative chest wall deformities. Long-term outcome is mandatory to confirm these preliminary results.

Objectives Calretinin immunohistochemistry (IHC) with slight submucosal positivity (variant) has been reported in short forms of Hirschsprung disease (HD). The first aim of our study was to confirm this variant being a pretransitional sign. The second was to evaluate if its presence on suction rectal biopsy was reliable enough for surgical planning. Methods We performed a monocentric retrospective study of all rectosigmoid HD between 2009 and 2014. Suction rectal biopsy defined two groups of calretinin results: P− group with no staining and P+ group with slight positivity. P− group final resection specimen was retrospectively reanalyzed looking for the variant to appear within the aganglionic bowel. P+ group surgical management was analyzed in terms of initial symptoms, radiological results, type of surgery and outcome, before and after formal identification of the variant by our pathologists (2011). Results Overall, 54 patients with rectosigmoid HD were included from 2009 to 2014. In the P− group (48.2%), the variant pattern finally appeared on all surgical resection specimens, 1 cm before the transitional zone (minimum–maximum: 0–5 cm). In the P+ group, 46% of these patients had peroperative biopsies before the transanal pull through before 2011 against 10% after 2011, with 100% of ganglionic coloanal anastomosis and similar outcome. Conclusion We confirmed our hypothesis of this varied pattern of calretinin being a pretransitional sign only visible on rectal suction biopsies in short segment HD and reliable enough to plan direct transanal pull through.

International audience; In this paper, we propose a patch-based deep learning ap-proach to segment pelvic vessels in 3D MRI images of pediatric patients.For a given T2 weighted MRI volume, a set of 2D axial patches areextracted using a limited number of user-selected landmarks. In orderto take into account the volumetric information, successive 2D axialpatches are combined together, producing a set of pseudo RGB colorimages. These RGB images are then used as input for a convolutionalneural network (CNN), pre-trained on the ImageNet dataset, which re-sults into both segmentation and vessel labeling as veins or arteries. Theproposed method is evaluated on 35 MRI volumes of pediatric patients,obtaining an average segmentation accuracy in terms of Average Sym-metric Surface Distance of ASSD = 0.89 ± 0.07 mm and Dice Index ofDC = 0.79 ± 0.02.

Enterococcus faecalis is an opportunistic multidrug-resistant human pathogen causing severe nosocomial infections. Previous investigations revealed that the CroRS two-component regulatory pathway likely displays a pleiotropic role in E. faecalis, involved in virulence, macrophage survival, oxidative stress response as well as antibiotic resistance. Therefore, CroRS represents an attractive potential new target for antibiotherapy. In this report, we further explored CroRS cellular functions by characterizing the CroR regulon: the 'domain swapping' method was applied and a CroR chimera protein was generated by fusing the receiver domain from NisR to the output domain from CroR. After demonstrating that the chimera CroR complements a croR gene deletion in E. faecalis (stress response, virulence), we conducted a global gene expression analysis using RNA-Seq and identified 50 potential CroR targets involved in multiple cellular functions such as cell envelope homeostasis, substrate transport, cell metabolism, gene expression regulation, stress response, virulence and antibiotic resistance. For validation, CroR direct binding to several candidate targets was demonstrated by EMSA. Further, this work identified alr, the gene encoding the alanine racemase enzyme involved in E. faecalis resistance to D-cycloserine, a promising antimicrobial drug to treat enterococcal infections, as a member of the CroR regulon.

This study aimed to examine the choice pregnant women make about the amount of fetal genetic information they want from chromosome microarray. Women having invasive prenatal testing in the absence of fetal structural abnormality were recruited in Victoria, Australia. A decision aid for women described ‘targeted’ analysis as reporting only copy number variants implicated in a highly penetrant and well-described phenotype and ‘extended’ as additionally reporting variants of uncertain or unknown significance. Participant’s choice and demographics were collected by survey before chorionic villus sampling or amniocentesis; psychological data were also collected then and again about 10 days after receiving results. High-resolution single-nucleotide polymorphism array analysis was performed, and a clinical review committee assessed variants for reporting before returning results to participants. Sixty-six participants (59.5%) chose extended analysis and 45 (40.5%) targeted. Choosing extended information was associated with (1) indication for prenatal diagnosis: maternal age alone (adjusted odds ratio (adjOR) 9.6, 95% confidence interval (CI): 1.4–66.0, p= 0.02), or ‘other’ indication (adjOR 7.1, 95% CI: 1.5–33.1, p= 0.01)); (2) >12 months to conceive (adjOR 4.1, 95% CI: 1.0–17.7, p= 0.05); and (3) Asian background (adjOR 4.67, 95% CI: 1.0–21.0, p= 0.04). No adverse psychological impact occurred in either group. We conclude that offering pregnant women different levels of fetal genetic analysis is warranted, alongside decision support.

International audience; In this paper we address the problem of bone segmentation in MRIimages of children, in the region of the pelvis. To cope with the complex structure of the bones in this region and their changing topologyduring growth, we propose a method relying on 3D bone templates.These models are built from 3D CT images. For a given MRI volume, the closest template is chosen and registered on the MRI data.This leads to an initial segmentation which is then refined using a deformable model approach, where the regularization parameters depend on the local curvature, and the landmarks used during the registration are fixed anchors during the deformation. This approach wassuccessfully applied to 15 MRI volumes of children between 1 and18 years old, with an average accuracy in terms of medium distanceof M D = 1.17 ± 0.29 mm and Dice Index of DC = 0.81 ± 0.04.

Objective Urinary and faecal continence are key challenges goal of cloacal malformation management. Most well-known prognostic factors are the length of common channel (CC) and the presence of a sacral defect, but the impact of associated spinal dysraphism is less well documented. The aim of this study was to investigate the impact of different types of dysraphism on urinary and faecal continence in this patient population. Materials and methods From 1991 to 2011, charts and office notes of 25 patients with cloacal malformation were retrospectively reviewed. At last clinic visit, urinary and faecal continence status according to Krickenbeck criteria were correlated with the length of CC, the presence of a sacral defect (sacral ratio), and the presence of different types of spinal cord dysraphism using magnetic resonance imaging (MRI) and Fisher's exact test. Results Mean follow-up was 8 years (4 months–21 years). The sacral ratio was abnormal (below 0.74) in 18 cases out of 25 (72%). MRI review showed normal spinal cord in eight out of 23 cases (Group 1), spinal cord anomaly in 15 out of 23 cases (65%) including nine cases of tethered cord complex (Group 2) and six cases of a short spinal cord (Group 3). While statistical analysis showed a difference regarding urinary prognosis between the groups (p = 0.005), no significant difference was found regarding faecal prognosis. None of the six patients with short spinal cord were continent for both urinary and faecal prognosis. Conclusions This is the first study, which highlights the impact of different types of spinal dysraphism on functional outcome in patients with cloaca. Short spinal cord seemed to carry the worst prognosis. A prospective study with a larger series is mandatory to confirm these preliminary results.

The purpose of this study is to confirm the effectiveness of total laparoscopic treatment of common bile duct (CBD) stones in children. All children who were treated in our department for cholelithiasis were reviewed from 1996 to 2013. Data collection focused on children with CBD stones, including age, sex, symptoms at diagnosis, hepatic and pancreatic blood tests results, US scan results, etiology, detailed surgical technique, operative time, length of hospital stay, complications, and stone-free status or not, at last follow-up. 551 children were treated for cholelithiasis and had undergone laparoscopic cholecystectomy. Among those, 36 children (6.5 %) presented with CBD stones with a mean age at symptom onset of 10.4 years (min–max: 4 months–18 years). A majority of the patients presented with hemolytic disease (61 %). In 55 % of the cases, cholangiography alone or simple serum saline flush of the biliary tree was sufficient to obtain a stone-free CBD. Additional maneuvers with Dormia basket or Fogarty catheter led to 72 % of success rate. In 9 cases (25 %) of failure of the procedure, 6 patients underwent endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic sphincterotomy (ES), 1 patient was re-operated at day1 for hemorrhage, and 2 patients were followed by US scan with spontaneous evacuation of CBD stones. Mean follow-up was of 2 years (min–max: 1 month–5 years). All patients were stone free at last clinical and radiological evaluation. A one-stage total laparoscopic treatment of common bile duct stones in children is a safe, feasible, reproducible, and efficient procedure in 72 % of the cases. This rate could be upgraded by a combination of laparoscopic and endoscopic technique during the same anesthesia and preserving Oddi sphincter function. These minimal invasive techniques still need to be developed in children.

Decisions to undergo invasive prenatal diagnostic procedures can be anxiety provoking. Individuals receive information about these procedures in one of three modalities: written text, audio (verbal description), or video. We examined whether modality influences emotional responses and testing decisions, and whether trait anxiety, a disposition linked with heightened sensitivity to threatening information, moderates these effects. New Zealand adults (N = 176) completed a trait anxiety measure before random allocation to view a text, audio, or video message about amniocentesis and chorionic villus sampling. Participants completed measures of child related worry, anticipated emotional distress, anticipated coping efficacy, perceived likelihood of miscarriage, and testing interest. High-anxious individuals reported greater distress and lower coping efficacy in response to the video message compared to the audio message. They also reported greater miscarriage likelihood in response to the video message compared to the text message. These findings suggest that use of video, assumed to be most informative for educating patients, could induce greater distress about prenatal testing in individuals prone to anxiety.

Laparoscopic pyeloplasty in children remains controversial and is not included in most pediatric urology centers because of technical difficulties and lack of long-term results.To critically analyze our 10-yr experience with the retroperitoneal approach (RA), with a particular interest on the impact of the learning curve in a teaching center.Patients who underwent pyeloplasty between 1999 and 2010 at our institution were reviewed (n=390). The diagnosis of ureteropelvic junction obstruction was confirmed by ultrasound and technetium Tc 99m mercaptoacetyltriglycine-3 renal scan or magnetic resonance imaging; the same criteria were used to evaluate the outcome. The lateral RA was selected in children1 yr of age without abnormal migration or fusion of the kidney (n=104).Dismembered pyeloplasty and anastomosis were performed using running monofilament 5-0 or 6-0 absorbable suture. All were drained by double-J stent except 20 cases drained by external transanastomotic stent.We assessed intra- and postoperative morbidity and analyzed the teaching of technique and learning curve. Data are expressed as medians and interquartile range (25th, 75th percentiles) for quantitative variables.Median age was 6.2 yr (2.2-10.3). Thirty-three patients had crossing vessels. Median operative time was 185 min (160-235). Median hospital stay was 2 d (1-2). Redo pyeloplasty was needed in only two children (2%). Median follow-up was 2.1 yr (1.4-4.1). Operative time was3 h after 35 cases. After 30 cases performed by the same surgeon, standardization of the technique was feasible, which helped in the teaching process because 50% of the final 30 cases were done by trainees.Retroperitoneal dismembered laparoscopic pyeloplasty is a safe, reliable, and efficient procedure with an excellent outcome in selected children according to their indications and age, and the experience of the surgical team. Even if the transmission to trainees is successful, it is still a long learning process and remains a challenging task for a teaching center.

La chirurgia del testicolo non disceso e un intervento molto frequente in chirurgia urologica pediatrica. Realizzata il piu delle volte in ambulatorio quando il testicolo e palpabile nel canale inguinale, essa fa ricorso anche alla chirurgia laparoscopica quando il testicolo e in posizione alta intraddominale. La valutazione preoperatoria della posizione del testicolo e, prima di tutto, clinica. Essa puo essere aiutata dall’ecografia o dall’angio-RM in caso di dubbio e deve essere completata da un bilancio endocrino nel caso di testicolo non palpabile bilaterale. Le sfide del ripristino della posizione del testicolo in sede intrascrotale riguardano, a lungo termine, la fertilita di questi bambini e il rischio di cancerizzazione del testicolo non disceso.

La cirugia de la criptorquidia es un procedimiento muy frecuente en cirugia urologica pediatrica. En la mayoria de los casos se realiza de forma ambulatoria cuando el testiculo es palpable en el trayecto inguinal y tambien puede recurrirse a la cirugia laparoscopica cuando el testiculo tiene una posicion alta intraabdominal. La evaluacion preoperatoria de la posicion del testiculo es sobre todo clinica. En caso de duda, se puede utilizar la ecografia y la angiografia por resonancia magnetica (angio-RM), y habra que completarla con un estudio endocrino ante un testiculo no palpable bilateral. Los objetivos del restablecimiento de la posicion intraescrotal del testiculo consisten, a largo plazo, en la fertilidad de estos ninos y en evitar el riesgo de malignizacion del testiculo criptorquidico.

The correlation between radiographic transition zone on contrast enema in Hirschsprung’s disease and the total length of aganglionosis is known to be inaccurate. The aim of our study was to analyse this correlation more precisely to improve preoperative planning of the corrective surgery. From 1998 to 2009, 79 patients were operated on for Hirschsprung’s disease. All available preoperative contrast enemas (n = 61) had been single blind reviewed by the same radiologist who defined the radiographic transition zone when present in vertebral level. Four groups were determined (rectal, rectosigmoid, long segment, and absence of transition zone) and by Kappa coefficient of agreement correlated to the length of aganglionosis in the pathological report. Radiological findings were concordant with the specimen in pathology in 8 cases of 19 in rectal form (42 %), in 20 cases of 35 in rectosigmoid form (57 %), in all 6 cases of long-segment form (100 %), in the 2 cases of total colonic form (100 %) with a global agreement of 58.1 %, κ = 0.39 CI [0.24; 0.57]. Correlation between level of radiographic transition zone on contrast enema and length of aganglionosis remains low. Systematic preoperative biopsy by coelioscopy or ombilical incision is mandatory.

Fur, the ferric uptake regulator, is a transcription factor that controls iron metabolism in bacteria. Binding of ferrous iron to Fur triggers a conformational change that activates the protein for binding to specific DNA sequences named Fur boxes. In Helicobacter pylori, HpFur is involved in acid response and is important for gastric colonization in model animals. Here we present the crystal structure of a functionally active HpFur mutant (HpFur2M; C78S-C150S) bound to zinc. Although its fold is similar to that of other Fur and Fur-like proteins, the crystal structure of HpFur reveals a unique structured N-terminal extension and an unusual C-terminal helix. The structure also shows three metal binding sites: S1 the structural ZnS₄ site previously characterized biochemically in HpFur and the two zinc sites identified in other Fur proteins. Site-directed mutagenesis and spectroscopy analyses of purified wild-type HpFur and various mutants show that the two metal binding sites common to other Fur proteins can be also metallated by cobalt. DNA protection and circular dichroism experiments demonstrate that, while these two sites influence the affinity of HpFur for DNA, only one is absolutely required for DNA binding and could be responsible for the conformational changes of Fur upon metal binding while the other is a secondary site.

What's already known about this topic? Women prefer to receive information about prenatal testing options face-to-face from a health professional.Increasing numbers of people are accessing health-related information online. What does this study add?In spite of increased online access of health information, both women and partners still prefer to receive information about prenatal testing options face-to-face.High rates of information seeking were observed among pregnant women and partners, despite seemingly high satisfaction with information provided.

With rapid advances in genetic testing for disease susceptibility, behavioral medicine faces significant challenges in identifying likely patterns of use, how individuals interpret test results, and psychosocial and health impacts of testing. We review recent research on these psychosocial aspects of genetic testing for disease risk.Individuals exhibit limited sensitivity in their perceptions of genetic risk information, and mental representations of disease risk appear to guide testing perceptions and behavioral responses. Motivations to undergo testing are complex, and efforts to develop decision aids are underway. Findings on psychological and behavioral impacts of genetic testing vary markedly, with some evidence of minimal or positive effects and other evidence indicating negative consequences that may be undetectable using common measures of general well being. Recent evidence suggests that genetic risk information can motivate health behavior change. Research demonstrates wide-ranging influences of testing on family dynamics, and use of genetic testing with children is of increasing concern.More research is needed to determine how to structure health communications and counseling to motivate informed use, promote positive responses, and optimize behavior change. Given the ramifications of genetic information for families, personalized genomics will demand a shift toward a family-based healthcare model.

The aim of this exploratory study was to measure attitudes towards various applications of real and hypothetical reproductive technologies for humans, including prenatal gender selection. A total of 121 undergraduate university students completed a questionnaire measuring knowledge, interest, trust, risks and benefits, and attitudes towards reproductive technologies for humans. An exploratory factor analysis showed that participants rated the use of these technologies as unacceptable if it was for personal enhancement but acceptable for “medically useful” applications. Participants also reported not having a gender preference for their (hypothetical) unborn child, were they to use prenatal gender selection, an application very few approved of. Results failed to support a general desire to use prenatal gender selection or to hypothetically favour one gender over the other. Attitudes towards reproductive technologies cannot be simply summarised in a “pro or against” manner as they heavily depend on...

The intracellular survival in mouse peritoneal macrophages of 8 Enterococcus faecalis response regulator mutants was tested to assess if the corresponding 2-component signal transduction systems (TCS) are involved in the ability of E. faecalis to survive in macrophages. Three mutants (err04, err05 and err06) are more susceptible than the wild-type JH2-2 strain and 1 is more resistant (err10). Then, characterization of the TCS Err04-Ehk04 and Err06-Ehk06 reveals that the first (homolog of PhoP-PhoR of Bacillus subtilis) is induced in phosphate deprivation conditions, regulates its own expression and plays a role in the expression of pstF encoding a phosphate-binding protein. The Err06-Ehk06 is involved in oxidative stress response. A mutation in the err06 gene increases sensitivity of the bacterium to H2O2. The err06-ehk06 operon is induced by H2O2 stress and controlled by 2 transcriptional start sites, of which 1 is specifically active in oxidative stress conditions. We also demonstrated that the expression of the catalase gene (kat) is partly dependant of the Err06-Ehk06 TCS.

Using a modified random arbitrarily primed PCR approach, the operon encoding the Enterococcus faecalis JH2-2 CroRS two-component regulatory system was shown to be repressed during stationary phase, and a CroRS-regulated operon ( glnQHMP ) was identified. Gel retardation assays showed that the CroR regulator binds specifically to the glnQHMP promoter.