Laurent Fourcade

Esophageal atresia: Data from a national cohort

PURPOSE A prospective national register was established in 2008 to record all new cases of live-birth newborns with esophageal atresia (EA). This epidemiological survey was recommended as part of a national rare diseases plan. METHODS All 38 national centers treating EA participated by completing for each patient at first discharge a questionnaire validated by a national committee of experts. Data were centralized by the national reference center for esophageal anomalies. Quantitative and qualitative analyses were performed, with P-values of less than 0.05 considered statistically significant. Results of the 2008-2009 data collection are presented in this report. RESULTS Three hundred seven new living cases of EA were recorded between January 1, 2008, and December 31, 2009. The male/female sex ratio was 1.3, and the live-birth prevalence of EA was 1.8 per 10,000 births. Major characteristics were comparable to those reported in the literature. Survival was 95%, and no correlation with caseload was noted. CONCLUSIONS Epidemiologic surveys of congenital anomalies such as EA, which is a rare disease, provide valuable data for public health authorities and fulfill one important mission of reference centers. When compared with previous epidemiological data, this national population-based registry suggests that the incidence of EA remains stable.

How to successfully implement a robotic pediatric surgery program: lessons learned after 96 procedures.

BackgroundBoth our teams were the first to implement pediatric robotic surgery in France. The aim of this study was to define the key points we brought to light so other pediatric teams that want to set up a robotic surgery program will benefit.MethodsWe reviewed the medical records of all children who underwent robotic surgery between Nov 2007 and June 2011 in both departments, including patient data, installation and changes, operative time, hospital stay, intraoperative complications, and postoperative outcome. The department’s internal organization, the organization within the hospital complex, and cost were evaluated.ResultsA total of 96 procedures were evaluated. There were 38 girls and 56 boys with average age at surgery of 7.6 years (range, 0.7–18 years) and average weight of 26 kg (range, 6–77 kg). Thirty-six patients had general surgery, 57 patients urologic surgery, and 1 thoracic surgery. Overall average operative time was 189 min (range, 70–550 min), and average hospital stay was 6.4 days (range, 2–24 days). The procedures of 3 patients were converted. Median follow-up was 18 months (range, 0.5–43 months). Robotic surgical procedure had an extra cost of €1934 compared to conventional open surgery.ConclusionsOur experience was similar to the findings described in the literature for feasibility, security, and patient outcomes; we had an overall operative success rate of 97 %. Three main actors are concerned in the implementation of a robotic pediatric surgery program: surgeons and anesthetists, nurses, and the administration. The surgeon is at the starting point with motivation for minimally invasive surgery without laparoscopic constraints. We found that it was possible to implement a long-lasting robotic surgery program with comparable quality of care.

Does prenatal diagnosis modify neonatal treatment and early outcome of children with esophageal atresia

OBJECTIVE Our study aimed at (1) evaluating neonatal treatment and outcome of neonates with either a prenatal or a postnatal diagnosis of esophageal atresia (EA) and (2) analyzing the impact of prenatal diagnosis on outcome based on the type of EA. STUDY DESIGN We conducted a population-based study using data from the French National Register for infants with EA born from 2008-2010. We compared prenatal, maternal, and neonatal characteristics among children with prenatal vs postnatal diagnosis and EA types I and III. We defined a composite variable of morbidity (anastomotic esophageal leaks, recurrent fistula, stenosis) and death at 1 year. RESULTS Four hundred sixty-nine live births with EA were recorded with a prenatal diagnosis rate of 24.3%; 82.2% of EA type I were diagnosed prenatally compared with 17.9% of EA type III (P < .001). Transfer after birth was lower in case of prenatal diagnosis (25.6% vs 82.5%; P < .001). The delay between birth and first intervention did not differ significantly among groups. The defect size was longer among the prenatal diagnosis group (2.61 vs 1.48 cm; P < .001). The composite variables were higher in prenatal diagnosis subset (44% vs 27.6%; P = .003) and in EA type I than in type III (58.1% vs 28.3%; P < .001). CONCLUSION Despite the excellent survival rate of EA, cases with antenatal detection have a higher morbidity rate related to the EA type (type I and/or long gap). Even though it does not modify neonatal treatment and the 1-year outcome, prenatal diagnosis allows antenatal parental counselling and avoids postnatal transfers.

Inguinal hernia in premature boys: Should we systematically explore the contralateral side?☆ , ☆☆

OBJECTIVE Bilateral surgery has been largely advocated in premature boys with unilateral inguinal hernia owing to the high incidence of contralateral patent processus vaginalis. Recently, the potential morbidity of herniotomy in low birth-weight babies and the progress in pediatric anesthesia questioned this attitude. This study aims to evaluate the incidence of contralateral metachronous hernia in a large series of premature boys and to compare the morbidity of preventive versus elective surgery. METHODS This retrospective multicenter analysis of 964 premature boys presenting with unilateral inguinal hernia operated from 1998 to 2012 included 557 infants who benefited from a unilateral herniotomy and 407 from a bilateral herniotomy (median follow-up 12months). RESULTS Contralateral metachronous hernia after unilateral surgery occurred in 11% (n=60) without significant difference according to the initial symptomatic side (9.5% on right vs 13% on left, p>0.05). Postoperative morbidity on the contralateral side was higher after preventive surgery than elective surgery with metachronous hernia (2.45% versus 0.9%, p=0.05) especially for secondary cryptorchidism (1% vs 0%, p=0.03). Despite the risk of metachronous incarcerated hernia, elective surgery did not increase the rate of testicular hypotrophy on the opposite side (0.7%, vs 0.7%, p>0.05). CONCLUSION Systematic bilateral herniotomy is unnecessary in almost 90% of patients and has a significant morbidity. Secondary surgery for metachronous hernia does not increase the risk of testicular lesion and even reduces the risk of secondary cryptorchidism. These results, along with the risk of hypofertility reported after bilateral surgery, may justify treating only the symptomatic side in premature boys.

Fingolimod inhibits PDGF-B-induced migration of vascular smooth muscle cell by down-regulating the S1PR1/S1PR3 pathway

Platelet Derived Growth Factor (PDGF) and sphingosine-1-phosphate (S1P) pathways play a key role in mural cell recruitment during tumor growth and angiogenesis. Fingolimod, a S1P analogue, has been shown to exert antitumor and antiangiogenic properties. However, molecular targets and modes of action of fingolimod remain unclear. In this study, we confirmed the antagonizing action of S1P and PDGF-B on rat vascular smooth muscle cell (VSMCs) growth and migration. We then compared siRNA and/or fingolimod (100 nM) treatments on PDGFR-β, S1PR1 S1PR2 and S1PR3 expression. Fingolimod induced a 50% reduction in S1PR3 protein expression which was cumulative with that obtained with anti-S1PR3 siRNA. We found that siRNA-induced inhibition of both PDGFR-β and S1PR3 was the most effective means to block VSMC migration induced by PDGF-B. Finally, we observed that fingolimod treatment associated with anti-S1PR1 siRNA principally inhibited VSMC growth while in combination with anti-S1PR3 siRNA it strongly inhibited VSMC migration. These results suggest that for rat VSMCs, the PDGFR-S1PR1 pathway is predominantly dedicated to cell growth while PDGFR-S1PR3 stimulates cell migration. As an S1P analogue, fingolimod is considered a potent activator of S1PR1 and S1PR3. However, its action on the PDGFR-S1PR platform appears to be dependent on S1PR1 and S1PR3 specific downregulation. Considering that the S1P pathway has already been shown to exert various crosstalks with tyrosine kinase pathways, it seems of great interest to evaluate fingolimod potential in combination with the numerous tyrosine kinase inhibitors used in oncology.

In vitro 3D angiogenesis assay in egg white matrix: comparison to Matrigel, compatibility to various species, and suitability for drug testing.

In vitro angiogenesis assays are commonly used to assess pro- or anti-angiogenic drug properties. Extracellular matrix (ECM) substitutes such as Matrigel and collagen gel became very popular in in vitro 3D angiogenesis assays as they enable tubule formation by endothelial cells from culture or aortic rings. However, these assays are usually used with a single cell type, lacking the complex cellular interactions occurring during angiogenesis. Here, we report a novel angiogenesis assay using egg white as ECM substitute. We found that, similar to Matrigel, egg white elicited prevascular network formation by endothelial and/or smooth muscle cell coculture. This matrix was suitable for various cells from human, mouse, and rat origin. It is compatible with aortic ring assay and also enables vascular and tumor cell coculture. Through simple labeling (DAPI, Hoechst 33258), cell location and resulting prevascular network formation can easily be quantified. Cell transfection with green fluorescent protein improved whole cell visualization and 3D structure characterization. Finally, egg-based assay dedicated to angiogenesis studies represents a reliable and cost-effective way to produce and analyze data regarding drug effects on vascular cells.

Assessment of paediatric thoracic robotic surgery

OBJECTIVES Many studies have reported that robotic-assisted surgery is safe and feasible for paediatric cases. However, very few paediatric thoracic robotic cases have been described. The aim of this study was to share our preliminary experience with robot-assisted thoracic surgery (RATS). METHODS We reviewed our first, consecutive thoracic robotic procedures between January 2008 and December 2013. Data describing the perioperative and intraoperative periods were prospectively collected in two surgical paediatric centres and then retrospectively analysed. Operation time, completion rate, length of hospitalization and postoperative complications were compared with thoracoscopic results in the literature. RESULTS Eleven patients were operated on with the robot, and this included operations for oesophageal atresia (3), mediastinal cyst (4), diaphragmatic hernia (2), oesophagoplasty (1) and oesophageal myotomy (1). The mean age at surgery was 72 (range 0-204) months, and the mean weight was 24.4 (range 3.0-51.5) kg. Three of the operations were converted to thoracotomies. The total operation time was 190 (120-310) min, and the average length of hospital stay was 13 (3-35) days. RATS offers similar advantages to thoracoscopy for mediastinal cyst excision in patients weighing more than 20 kg. Appropriate patient positioning and trocar placement were necessary for neonatal patients and thereby resulted in longer preparation times. Despite cautious adjustments, technical feasibility was reduced for low-weight patients. CONCLUSIONS These data support mediastinal cyst excision as a suitable indication for larger children. Currently, there is a lack of evidence that lower weight children, and particularly neonates, are good candidates for RATS.

Delayed-onset Ureteral Obstruction and Calcification Masquerading as Renal Colic Following Deflux Injection

Vesicoureteral reflux is a common disorder in children, and its management has changed entirely as a result of widespread use of endoscopy procedures to inject filler materials. Complications with this type of treatment, particularly ureteral obstruction, are rare. Very few patients with delayed obstruction have been reported in the literature. We here present the case of an 8-year-old girl who exhibited symptoms of febrile renal colic and renal distension more than 5 years after undergoing endoscopic treatment. This is the first reported case of atypical late presentation combining pyelonephritis with ureteral obstruction and calcification.

Myenteric plexus alterations downstream from a prenatal intestinal obstruction in a rat model

The enteric nervous system maturation occurs during embryonic life and continues after birth. Some prenatal events on the digestive tract such as intestinal atresia have been shown to dramatically alter this maturation. Thus, we developed a fetal rat model of intestinal atresia by surgically obstructing the small bowel at embryonic day E18. Fetuses were removed at day E21, and small bowels sections were examined by immuno-histochemistry. Synaptophysin and smooth muscle actin staining was used to define the cellular aspect. Labeling revealed marked alterations of the myenteric plexus in the lower extremity of the occluded small bowel. At day E21, the myenteric plexus of the lower part and the 2 muscle layers surrounding it, retained the staining pattern observed at day E17. This cellular pattern was classified as: immature (aspect at day E17) vs. mature (aspect of day E21) by 3 pathologists not familiar with the study. The number of samples with an immature cellular pattern at the lower end of the occluded bowel was different from that observed for the upper end (Mac Nemar test, p<0.008). Our study suggests that a prenatal obstruction induces a maturation delay of the myenteric plexus downstream of the obstruction. This might be important for pediatric purposes.

A new rat model of prenatal bowel obstruction: development and early assessment

PURPOSE Although intestinal motility disorders often complicate the postoperative surgical management of newborns with congenital intestinal atresia, their pathogenesis remains unclear. Animal models of prenatal intestinal obstruction have been mainly developed in the lamb and the chicken. Despite new insights brought by these models, they have one or more limitations, such as high fetal mortality rates, high costs, long gestation periods, and an insufficient number of fetuses per litter. Moreover, some species are phylogenetically distant from mammals. METHODS We developed a reproducible model of prenatal intestinal obstruction in the rat to study the histologic changes induced by the obstruction. We report, the technical devices and the first assessment of this atresia model in a didactic way to allow other researchers to easily reproduce the model. RESULTS Prenatal intestinal obstructions in this study fulfilled all the macroscopic and histologic criteria usually listed by other models of prenatal intestinal obstruction that have been developed in other species. Furthermore with our model, we obtained a high success rate at a low cost. CONCLUSIONS We presented in this study a reproducible model of prenatal intestinal obstruction in the rat with the macroscopical and histologic features of prenatal intestinal obstruction.