Predictors of the Performance of Early Antireflux Surgery in Esophageal Atresia.

OBJECTIVE: To identify predictors of and factors associated with the performance of antireflux surgery during the first year of life in children born with esophageal atresia. STUDY DESIGN: All patients were included in a French registry for esophageal atresia. All 38 multidisciplinary French centers completed questionnaires about perinatal characteristics and one-year outcome for children born with esophageal atresia. RESULTS: Of 835 infants with esophageal atresia born in France from 2010 to 2014, 682 patients, excluding those with long-gap esophageal atresia, were included. Three patients had type I, 669 had type III, and 10 had type IV esophageal atresia. Fifty-three children (7.8%) received fundoplication during the first year of life. The median age at the time of the end-to-end esophageal anastomosis was 1.1 day (range 0-15). Multivariate analysis identified three perioperative factors that predicted the need for early antireflux surgery: anastomotic tension (P = .004), associated malformations (P = .019), and low birth weight (P = .018). Six other factors, measured during the first year of life, were associated with the need for antireflux surgery: gastroesophageal reflux (P < .001), anastomotic stricture (P < .001), gastrostomy (P < .001), acute life-threatening event (P = .002), respiratory complications (P = .045), and poor nutritional status (P < .001). CONCLUSIONS: Gastroesophageal reflux disease, low birth weight, poor nutrition, and surgical anastomosis difficulties predicted the performance of antireflux surgery in the first year of life in infants with esophageal atresia.

How to Explore Fetal Sacral Agenesis Without Open Dysraphism: Key Prenatal Imaging and Clinical Implications.

The estimated prevalence of fetal caudal dysgenesis is 1 per 100,000 births. The functional prognosis of sacral agenesis is dominated by the large spectrum of associated caudal malformations. Except for cases associated with hydrocephalus secondary to open spinal dysraphism or chromosomal anomalies, association with mental deficiency is rare. We propose a systematic prenatal approach to cases of fetal sacral agenesis based on 9 etiologic items: clinical context, type of sacral dysgenesis, associated spinal cord malformations, mobility of lower limbs, investigation of the presacral region, analysis of the gastrointestinal tract, analysis of the genitourinary tract, associated vertebral defects, and cytogenetic analysis.

Is Nephron Sparing Surgery Justified in Wilms Tumor With Beckwith-Wiedemann Syndrome or Isolated Hemihypertrophy?

BACKGROUND: Patients with Beckwith-Wiedemann syndrome (BWS) or isolated hemihypertrophy (HH) treated for a Wilms tumor (WT) carry an increased risk of developing metachronous lesion. There are no guidelines on precise indications for nephron sparing surgery (NSS) in unilateral WT (UWT). The objective of this retrospective study was to delineate the indications of NSS in patients with BWS/HH treated for WT and to evaluate their outcome. PROCEDURE: All cases of BWS/HH treated for a WT according to SIOP protocols from 1980 to 2013 were reviewed. Patients were divided into two groups (G): isolated UWT (G1) and bilateral lesions (G2) with two subgroups: bilateral tumors suspected of malignancy (G2a), and unilateral tumor suspected of malignancy with contralateral nephroblastomatosis (G2b). RESULTS: Forty-six patients were included (34 G1, three G2a, and nine G2b). Nine NSS and 25 total nephrectomies (TN) were performed in G1, two bilateral NSS and one NSS with contralateral TN in G2a, and eight NSS and one TN in G2b. The 3-year event-free survival was 92.3% (95% CI [77.9-97.5%]). One death occurred after a local relapse following a TN for a stage III stromal WT (G1) and another after a combined local and distant relapse following a NSS for a stage I diffuse anaplastic WT (G2b). There were two metachronous WT (4%), 3 years after a TN (G1) and 12 years after a NSS (G2b). CONCLUSIONS: NSS is recommended in bilateral WT and may be an option in selected UWT patients with BWS/HH because it was not associated with an increased risk of local relapse.

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.

Clinical Effectiveness of Transversus Abdominis Plane (TAP) Block versus Local Anesthesia Wound Infiltration for Postoperative Pain Relief After Laparoscopic Appendicectomy in Children: A Study Protocol for a Multicenter Double-Blind Randomized Controlled Phase III Trial.

Purpose: Postoperative pain relief after laparoscopic appendicectomy is a key determinant of early rehabilitation in children. Recent guidelines recommend performing either a transversus abdominis plane (TAP) block or local anesthesia (LA) wound infiltration as part of multimodal postoperative analgesia after appendectomy. To date, the clinical effectiveness of TAP block versus LA wound infiltration has never been compared. The hypothesis of this study is that the TAP block may provide a greater opioid-sparing effect after laparoscopic appendicectomy in children than LA wound infiltration. Study Design and Methods: We designed a multicenter double-blind randomized controlled phase III trial and aim to include 110 children who undergo laparoscopic appendicectomy. Children are randomized to receive either TAP block (TAP group) or LA wound infiltration (infiltration group). Multimodal analgesia is standardized in the two groups using the same protocol, which includes the stepwise prescription of paracetamol, phloroglucinol, ketoprofene, and nalbuphine according to the hetero-evaluation of pain performed by the nurses who were blinded to the treatment allocated using the validated FLACC scale. The primary outcome is the total dose of nalbuphine administered within 24 hours after surgery. Discussion: No study has specifically compared the clinical effectiveness of TAP block versus LA wound infiltration for postoperative pain relief after laparoscopic appendectomy in children. This paper describes the protocol for a randomized trial that addresses this issue. The results of this trial will be useful for editing guidelines with a higher level of evidence on this topic.

Human mesenchymal stem cells reprogram adult cardiomyocytes toward a progenitor-like state through partial cell fusion and mitochondria transfer.

Because stem cells are often found to improve repair tissue including heart without evidence of engraftment or differentiation, mechanisms underlying wound healing are still elusive. Several studies have reported that stem cells can fuse with cardiomyocytes either by permanent or partial cell fusion processes. However, the respective physiological impact of these two processes remains unknown in part because of the lack of knowledge of the resulting hybrid cells. To further characterize cell fusion, we cocultured mouse fully differentiated cardiomyocytes with human multipotent adipose-derived stem (hMADS) cells as a model of adult stem cells. We found that heterologous cell fusion promoted cardiomyocyte reprogramming back to a progenitor-like state. The resulting hybrid cells expressed early cardiac commitment and proliferation markers such as GATA-4, myocyte enhancer factor 2C, Nkx2.5, and Ki67 and exhibited a mouse genotype. Interestingly, human bone marrow-derived stem cells shared similar reprogramming properties than hMADS cells but not human fibroblasts, which suggests that these features might be common to multipotent cells. Furthermore, cardiac hybrid cells were preferentially generated by partial rather than permanent cell fusion and that intercellular structures composed of f-actin and microtubule filaments were involved in the process. Finally, we showed that stem cell mitochondria were transferred into cardiomyocytes, persisted in hybrids and were required for somatic cell reprogramming. In conclusion, by providing new insights into previously reported cell fusion processes, our data might contribute to a better understanding of stem cell-mediated regenerative mechanisms and thus, the development of more efficient stem cell-based heart therapies.

ePTFE-based biomedical devices: An overview of surgical efficiency.

Polytetrafluoroethylene (PTFE) is a ubiquitous material used for implants and medical devices in general because of its high biocompatibility and inertness: blood vessel, heart, table jawbone, nose, eyes, or abdominal wall can benefit from its properties in case of disease or injury. Its expanded version, ePTFE is an improved version of PTFE with better mechanical properties, which extends its medical applications. A material as frequently used as ePTFE with these exceptional properties deserves a review of its main uses, developments, and possibility of improvements. In this systematic review, we examined clinical trials related to ePTFE-based medical devices from the literature. Then, we excluded all trials using ePTFE as a control to test other devices. ePTFE-coated stents, hemodialysis and bypass grafts, guided bone and tissue regeneration membranes, hernia and heart repair and other devices are reviewed. The rates of success using these devices and their efficiency compared to other materials used for the same purposes are reported. ePTFE appears to be more or just as efficient compared to them. Some success rates remain low, suggesting the need of improvement ePTFE for medical applications.

Risk prediction in surgery using case-based reasoning and agent-based modelization.

Managing the risks arising from the actions and conditions of the various elements that make up an operating room is a major concern during a surgical procedure. One of the main challenges is to define alert thresholds in a non-deterministic context where unpredictable adverse events occur. In response to this problematic, this paper presents an architecture that couples a Multi-Agent System (MAS) with Case-Based Reasoning (CBR). The possibility of emulating a large number of situations thanks to MAS, combined with analytical data management thanks to CBR, is an original and efficient way of determining thresholds that are not defined a priori. We also compared different similarity calculation methods (Retrieve phase of CBR). The results presented in this article show that our model can manage alert thresholds in an environment that manages data as disparate as infectious agents, patient's vitals and human fatigue. In addition, they reveal that the thresholds proposed by the system are more efficient than the predefined ones. These results tend to prove that our simulator is an effective alert generator. Nevertheless, the context remains a simulation mode that we would like to enrich with real data from, for example, monitoring sensors (bracelet for human fatigue, monitoring, etc).

Applications of Human Amniotic Membrane for Tissue Engineering.

An important component of tissue engineering (TE) is the supporting matrix upon which cells and tissues grow, also known as the scaffold. Scaffolds must easily integrate with host tissue and provide an excellent environment for cell growth and differentiation. Human amniotic membrane (hAM) is considered as a surgical waste without ethical issue, so it is a highly abundant, cost-effective, and readily available biomaterial. It has biocompatibility, low immunogenicity, adequate mechanical properties (permeability, stability, elasticity, flexibility, resorbability), and good cell adhesion. It exerts anti-inflammatory, antifibrotic, and antimutagenic properties and pain-relieving effects. It is also a source of growth factors, cytokines, and hAM cells with stem cell properties. This important source for scaffolding material has been widely studied and used in various areas of tissue repair: corneal repair, chronic wound treatment, genital reconstruction, tendon repair, microvascular reconstruction, nerve repair, and intraoral reconstruction. Depending on the targeted application, hAM has been used as a simple scaffold or seeded with various types of cells that are able to grow and differentiate. Thus, this natural biomaterial offers a wide range of applications in TE applications. Here, we review hAM properties as a biocompatible and degradable scaffold. Its use strategies (i.e., alone or combined with cells, cell seeding) and its degradation rate are also presented.

Gastroschisis in mice lacking aortic carboxypeptidase-like protein is associated with a defect in neuromuscular development of the eviscerated intestine.

Mice lacking aortic carboxypeptidase-like protein (ACLP) exhibit a gastroschisis (GS) like abdominal wall defect. The objectives of this study were to evaluate the pathophysiological features of GS in ACLP mice and to characterize the neuromuscular development of the eviscerated intestine (EI). ACLP mice were created by heterozygous mating from previously generated mice with targeted disruption of ACLP. Specimens were processed for H&E, and immunohistochemistry for smooth muscle cells [SMC, alpha-smooth muscle actin (alpha-SMA) antibody], interstitial cells of Cajal (ICC, c-kit-antibody), neural crest cells (NCC, Hox-b5-antibody), and enteric neurons (EN, PGP9.5-, alpha-internexin, and synaptophysin antibody). From 47 fetuses genotyped, 13 (27.7%) were wild type, 20 (42.5%) were heterozygous, and 14 (29.8%) were ACLP homozygous. In GS mice, expression of c-kit, Hox-b5, PGP-9.5, alpha-internexin, and synaptophysin were almost completely absent and only faint alpha-SMA expression was seen in the EI. In contrast, c-kit, Hox-b5, PGP9.5, alpha-internexin, synaptophysin, and alpha-SMA expression in intra-abdominal intestine in GS fetuses was the same as control intestine. The defect observed in ACLP mice closely resembles GS. Absence of ICC, NCC, EN, and immature differentiation of SMC supports an associated defect in neuromuscular development that is restricted to the EI.

Congenital Urethral Fistula: A Case Report and Literature Review.

Male congenital urethral fistula is an extremely rare condition. It is characterized by an abnormal opening of the ventral aspect of the penis. We report the case of a 1-month-old boy with congenital urethral fistula. We will describe the surgical technique, postoperative results, and literature review.

3D reconstruction of Wilms' tumor and kidneys in children: Variability, usefulness and constraints.

INTRODUCTION: Wilms' tumor (WT) is the most common type of malignant kidney tumor in children. Three-dimensional reconstructions can be performed pre-operatively to help surgeons in the planning phase. OBJECTIVES: The main objective of this study was to determine the variability of WT segmentation and 3D reconstruction. The secondary objectives were to assess the usefulness of these 3D reconstructions in the surgical planning phase and in the selection of patients for nephron-sparing surgery (NSS). METHODS: 14 scans from 12 patients were manually or semi-automatically segmented by 2 teams using 3D Slicer software. Inter-individual variability of 3D reconstructions was measured based on the Dice index. The utility of 3D reconstructions for the surgical planning was evaluated by 4 pediatric surgeons using a 5-point Likert scale. The possibility of undertaking NSS was evaluated according to the criteria defined in the Umbrella SIOP-RTSG 2016 protocol. RESULTS: Segmentation of the WT, healthy kidney, pathological kidney, arterial and venous vascularization could be performed for all of the patients in this study. Urinary cavities segmentation could only be performed for 5 out of 14 scans that had a delayed acquisition phase. The mean time required to carry out these segmentations was 8.6 h [3-15 h]. The mean Dice index for all of the scans was good (mean: 0.87; range [0.83-0.91]). Considering each anatomical structure, the Dice index was very good for the WT (mean: 0.95; range [0.91-0.97]) and the healthy kidney (mean: 0.95; range [0.93-0.96]), good for the pathological kidney (mean: 0.87; range [0.69-0.96]) and arterial vascularization (mean: 0.84; range [0.74-0.91]). The Dice index was lower than 0.8 for venous vascularization only (mean: 0.77; range [0.58-0.86]). All the surgeons who were interviewed agreed that the 3D reconstructions were realistic representations and useful for the surgical planning phase. The images reconstructed in 3D allowed most of the criteria defined by the Umbrella SIOP-RTSG 2016 protocol to be evaluated regarding the selection of patients who could benefit from NSS. CONCLUSION: The inter-individual variability of 3D reconstructions of WT is acceptable. Three-dimensional representation appears to assist surgeons with the surgical planning phase by allowing them to better anticipate the operative risks. 3D reconstructions can also be an additional tool to better select patients for NSS. However, the manual or semi-automatic method used is very time-consuming, making it difficult for a routinely use. Developing techniques to automate this segmentation process, therefore, appears to be essential if surgeons and radiologists are to use it in daily practice.

Induced membrane maintains its osteogenic properties even when the second stage of Masquelet's technique is performed later.

PURPOSE: Previous clinical studies have shown the effectiveness of bone repair using two-stage surgery called the induced membrane (IM) technique. The optimal wait before the second surgery is said to be 1 month. We have been successfully performing the IM technique while waiting an average of 6 months to carry out the second stage. We hypothesised that the IM maintains its beneficial capabilities, even at a later second stage, and that there is no relation between the speed of bone union and the wait between the first and second stage. We sought to explore the biological properties of 'older' IMs sampled to substantiate our clinical observations. METHODS: Thirty-four patients with a critical size defect were treated with the IM technique. In seven of these patients, pieces of the IM were collected 4.2-14.7 months after the first surgery. IM-derived cell phenotype and osteogenic potential were investigated using in vitro studies (n = 4) while IM nature and function were investigated by histology and immunohistochemistry (n = 3). RESULTS: The median wait before the second surgery was 5.8 months [range 1.2-14.7] and bone healing occurred at 7.6 months [range 2.5-49.9] for 26 patients. IMs aged 4.2-14.7 months contained mesenchymal stromal cells with in vitro osteogenic potential and corresponded to a multipotent tissue with osteogenic and chondrogenic capabilities contributing to osteogenesis over time. CONCLUSION: This preliminary study suggests the IM retains its powerful osteogenic properties over time and that waiting longer between the two surgeries does not delay bone union.

Correction to: Induced membrane maintains its osteogenic properties even when the second stage of Masquelet's technique is performed later.

The original version of this article unfortunately contained a mistake. The presentation and legends of Figs. 4 and 5 were incorrect. The corrected versions are given below. The original article has been corrected.

Dual intestinal anomalies in dizygotic twins.

We report on the case of two digestive malformations in dizygotic/dichorionic/diamniotic twins born at 31 weeks of gestation. The mother (gravida 1 para 0) was treated by hydroxychloroquine for systemic lupus erythematosus during pregnancy. Twin A presented an arch-like dilatation on antenatal ultrasounds, characteristic of segmental volvulus. After birth, twin B presented repeated vomiting on feeding, leading us to diagnose ileal atresia despite normal antenatal ultrasounds. Both twins underwent surgery and the postoperative period was uneventful. After 1 year of follow-up, the twins are in excellent health without digestive sequelae. Genetic testing for cystic fibrosis was negative. The placenta showed diffuse signs of hypoxia and ischaemia, indicating that the root cause was vascular. The pathophysiology of intestinal atresia is hypothesised to derive from a vascular incident during fetal development. We are therefore led to believe that an intrauterine vascular event is the most likely cause of the dual malformation.

Thoracic skeletal anomalies following surgical treatment of esophageal atresia. Lessons from a national cohort.

INTRODUCTION: Thoracotomy as surgical approach for esophageal atresia treatment entails the risk of deformation of the rib cage and consequently secondary thoracogenic scoliosis. The aim of our study was to assess these thoracic wall anomalies on a large national cohort and search for factors influencing this morbidity. MATERIALS AND METHODS: Pediatric surgery departments from our national network were asked to send recent thoracic X-ray and operative reports for patients born between 2008 and 2010 with esophageal atresia. The X-rays were read in a double-blind manner to detect costal and vertebral anomalies. RESULTS: Among 322 inclusions from 32 centers, 110 (34.2%) X-rays were normal and 25 (7.7%) displayed thoracic malformations, including 14 hemivertebrae. We found 187 (58.1%) sequelae of surgery, including 85 costal hypoplasia, 47 other types of costal anomalies, 46 intercostal space anomalies, 21 costal fusions and 12 scoliosis, with some patients suffering from several lesions. The rate of patients with these sequelae was not influenced by age at intervention, weight at birth, type of atresia, number of thoracotomy or size of the center. The rate of sequelae was higher following a classical thoracotomy (59.1%), whatever the way that thoracotomy was performed, compared to nonconverted thoracoscopy (22.2%; p=0.04). CONCLUSION: About 60 % of the patients suffered from a thoracic wall morbidity caused by the thoracotomy performed as part of surgical treatment of esophageal atresia. Minimally invasive techniques reduced thoracic wall morbidity. Further studies should be carried out to assess the potential benefit of minimally invasive approaches to patient pulmonary functions and on the occurrence of thoracogenic scoliosis in adulthood. LEVELS OF EVIDENCE: Level III retrospective comparative treatment study.

[To study the safety and effectiveness of heminephroureterectomy by horizontal lumbar posterior approach for duplicated systems in infants]. / Néphro-urétérectomie polaire pour duplication pyélo-urétérale par voie lombaire postérieure chez le nourrisson.

PURPOSE: To study the safety and effectiveness of heminephroureterectomy by horizontal lumbar posterior approach for duplicated systems in infants. MATERIALS AND METHODS: Thirty-three heminephroureterectomies by lumbar posterior approach were performed in 31 infants at a mean age of 6.7 +/- 5.5 months (range: 1 to 26 months) from January 1994 to December 2005. RESULTS: The mean operative time was 121 +/- 35 minutes (range: 60 to 190 minutes). No intra-operative complication was observed. Blood loss was minimal (< 20 ml) in all cases. The mean hospital stay was 4.6 days (range: 2 to 7 days). No postoperative complication (urinoma, infection or haemotoma) occurred. No atrophy or major functional loss of the remaining moiety was observed. The mean follow-up was 52.6 +/- 40 months (range: 1 to 151 months). CONCLUSIONS: The lumbar posterior approach is safe and reproducible and provides an obvious cosmetic benefit in comparison to the standard anterolateral lumbotomy. It represents a procedure of choice for open heminephroureterectomy in infants.

Quality assessment of economic evaluation studies in pediatric surgery: a systematic review.

PURPOSE: To assess economic evaluation studies (EES) in pediatric surgery and to identify potential factors associated with high-quality studies. METHODS: A systematic review of the literature using PubMed and Cochrane databases was conducted to identify EES in pediatric surgery published between 1 June 1993 and 30 June 2013. Assessment criteria are derived from the Drummond checklist. A high quality study was defined as a Drummond score ≥7. Logistic regression analysis was used to determine factors associated with high quality studies. RESULTS: 119 studies were included. 43.7% (n=52) of studies were full EES. Cost-effectiveness analysis was the most frequent (61.5%) type of full EES. Only 31.6% of studies had a Drummond score ≥7 and 73% of these were full EES. The factors associated with high quality were identification of costs (OR: 14.08; 95% CI: 3.38-100; p<0.001), estimation of utility value (OR: 8.13; 95% CI: 2.02-43.47; p=0.005) and study funding (OR: 3.50; 95% CI: 1.27-10.10; p=0.02). CONCLUSION: This review shows that the number and the quality of EES are low despite the increasing number of studies published in recent years. In the current context of budget constraints, our results should encourage pediatric surgeons to focus more on EES.