Phenotypic switch of smooth muscle cells in paediatric chronic intestinal pseudo-obstruction syndrome.

Smooth Muscle Cells (SMC) are unique amongst all muscle cells in their capacity to modulate their phenotype. Indeed, SMCs do not terminally differentiate but instead harbour a remarkable capacity to dedifferentiate, switching between a quiescent contractile state and a highly proliferative and migratory phenotype, a quality often associated to SMC dysfunction. However, phenotypic plasticity remains poorly examined in the field of gastroenterology in particular in pathologies in which gut motor activity is impaired. Here, we assessed SMC status in biopsies of infants with chronic intestinal pseudo-obstruction (CIPO) syndrome, a life-threatening intestinal motility disorder. We showed that CIPO-SMCs harbour a decreased level of contractile markers. This phenotype is accompanied by an increase in Platelet-Derived Growth Factor Receptor-alpha (PDGFRA) expression. We showed that this modulation occurs without origin-related differences in CIPO circular and longitudinal-derived SMCs. As we characterized PDGFRA as a marker of digestive mesenchymal progenitors during embryogenesis, our results suggest a phenotypic switch of the CIPO-SMC towards an undifferentiated stage. The development of CIPO-SMC culture and the characterization of SMC phenotypic switch should enable us to design therapeutic approaches to promote SMC differentiation in CIPO.

Prenatal imaging of genital defects: clinical spectrum and predictive factors for severe forms.

OBJECTIVES: To report the clinical spectrum of genital defects diagnosed before birth, identify predictive factors for severe phenotypes at birth, and determine the rate of associated malformations. PATIENTS AND METHODS: A retrospective study (2008-2017) of 4580 fetuses, identified prenatally with abnormalities evaluated by our Reference Center for Fetal Medicine, included cases with fetal sonographic findings of abnormal genitalia or uncertainty of fetal sex determination. Familial, prenatal and postnatal data were collected via a standardised questionnaire. RESULTS: In all, 61 fetuses were included. The positive predictive value (PPV) of the prenatal diagnosis of genital defects was 90.1%. Most cases were 46,XY-undervirilized boys, 42 cases (68.8%), which included 29 with mid-penile or posterior hypospadias, nine with anterior hypospadias, and epispadias, micropenis, scrotal transposition, and buried penis (one each). In all, 46,XX-virilized girls were identified in seven cases (11.5%), which included four with congenital adrenal hyperplasia, two with isolated clitoromegaly, and one with ovotestis. Other defects included prune belly syndrome and persistent cloaca (six cases). Early detection during the second trimester (58.1% vs 18.8%, P = 0.03), intra-uterine growth restriction (IUGR) (45.2% vs 9.1%, P = 0.06), and curvature of the penis (38.7% vs 0%, P = 0.02), were more frequently related to severe defects in male newborns. Associated malformations (14 cases, 22.9%) and genetic defects (six) were frequent in undervirilized boys. CONCLUSION: Prenatal imaging of genital defects leads to a wide range of phenotypes at birth. Its PPV is high and extra-urinary malformations are frequent. Early diagnosis during the second trimester, associated IUGR, and curvature of the genital tubercle, should raise suspicion of a severe phenotype and may justify delivery near a multidisciplinary disorders/differences of sex development team.

Prenatal diagnosis of antenatal midgut volvulus: Specific ultrasound features.

OBJECTIVE: To assess specific, direct, and indirect prenatal ultrasound features in cases of fetal midgut volvulus. METHODS: Retrospective case series of neonatal volvulus, based on postnatal and prenatal imaging findings that occurred from 2006-2017. Prenatal and postnatal signs including the specific "whirlpool sign" were computed. Postnatal volvulus was confirmed by pathology examination after surgery or neonatal autopsy. RESULTS: Thirteen cases of midgut volvulus were identified. Though not a specific sign, a decrease in active fetal movements was reported in eight patients (61.5%). The prenatal whirlpool sign was directly seen in 10 cases, while an indirect but suggestive sign, a fluid-filled level within the dilated loops, was present in five cases. No intestinal malrotation was observed. Pregnancy outcomes were two terminations of pregnancy, both associated with cystic fibrosis, one early neonatal death, three prenatal spontaneous regressions, and seven favorable outcomes after neonatal surgery with resection of midgut atresia. CONCLUSIONS: Identification of the whirlpool sign or of a fluid-filled level within the dilated loops improves the accuracy of ultrasound findings for suspected volvulus. In the absence of total volvulus (in cases of intestinal malrotation) or association with cystic fibrosis, the prognosis appears good.

Prenatal and postnatal evolution of isolated fetal splenic cysts.

OBJECTIVES: The aim of this study was to evaluate the prevalence, the prenatal, and postnatal evolution of isolated fetal splenic cysts. METHODS: All cases of suspected fetal splenic cyst or abdominal unidentified cyst discovered during routine ultrasound scan, from 2007 to 2017, and referred to a French tertiary care center, were retrospectively collected. For each case, several prenatal parameters and postnatal evolution were reported. RESULTS: Among 5450 cases of fetal anomalies, 14 patients (0.3%) had a prenatal diagnosis of fetal splenic cysts. Median gestational age at diagnosis was 30.1 weeks. A unique cyst was present in 78.6%, whereas 2 cysts were observed in 14.3% and 3 cysts in 7.1%. During the pregnancy, cysts remained the same (78.6%) or disappeared (21.4%). Ultrasound scans at 6 months of age found total disappearance of the cysts (36.4%), spontaneous reduction from 2 to 1 cyst (18.2%) or persistence of the cysts (45.4%). CONCLUSION: Fetal splenic cysts are rare images, always isolated, usually unique and mainly found during third trimester of pregnancy. Their evolution is to disappear spontaneously during pregnancy or at 6 months of age leaving only half of them to remain beyond that age but without any symptoms.

Anti-reflux surgery in children with congenital diaphragmatic hernia: A prospective cohort study on a controversial practice.

INTRODUCTION: Gastro-esophageal reflux disease (GERD) is the most frequent long-term morbidity of congenital diaphragmatic hernia (CDH) survivors. Performing a preventive fundoplication during CDH repair remains controversial. This study aimed to: (1) Analyze the variability in practices regarding preventive fundoplication; (2) Identify predictive factors for fundoplication. (3) Evaluate the impact of preventive fundoplication on gastro-intestinal outcomes in children with a CDH patch repair; METHODS: This prospective multi-institutional cohort study (French CDH Registry) included CDH neonates born in France between January 1st, 2010-December 31st, 2018. Patch CDH was defined as need for synthetic patch or muscle flap repair. Main outcome measures included need for curative fundoplication, tube feed supplementation, failure to thrive, and oral aversion. RESULTS: Of 762 CDH neonates included, 81 underwent fundoplication (10.6%), either preventive or curative. Median follow-up was 3.0 years (IQR: 1.0-5.0). (1) Preventive fundoplication is considered in only 31% of centers. The rates of both curative fundoplication (9% vs 3%, p = 0.01) and overall fundoplication (20% vs 3%, p < 0.0001) are higher in centers that perform preventive fundoplication compared to those that do not. (2) Predictive factors for preventive fundoplication were: prenatal diagnosis (p = 0.006), intra-thoracic liver (p = 0.005), fetal tracheal occlusion (p = 0.002), CDH-grade C-D (p < 0.0001), patch repair (p < 0.0001). After CDH repair, 8% (n = 51) required curative fundoplication (median age: 101 days), for which a patch repair was the only independent predictive factors identified upon multivariate analysis. (3) In neonates with patch CDH, preventive fundoplication did not decrease the need for curative fundoplication (15% vs 11%, p = 0.53), and was associated with higher rates of failure to thrive (discharge: 81% vs 51%, p = 0.03; 6-months: 81% vs 45%, p = 0.008), tube feeds (6-months: 50% vs 21%, p = 0.02; 2-years: 65% vs 26%, p = 0.004), and oral aversion (6-months: 67% vs 37%, p = 0.02; 1-year: 71% vs 40%, p = 0.03). CONCLUSIONS: Children undergoing a CDH patch repair are at high risk of requiring a curative fundoplication. However, preventive fundoplication during a patch repair does not decrease the need for curative fundoplication and is associated with worse gastro-intestinal outcomes in children. LEVEL OF EVIDENCE: II - Prospective Study.

Multicentric assessment of the safety of neonatal videosurgery.

BACKGROUND: Complex procedures for managing congenital abnormalities are reported to be feasible. However, neonatal videosurgery involves very specific physiologic constraints. This study evaluated the safety and complication rate of videosurgery during the first month of life and sought to determine both the risk factors of perioperative complications and the most recent trends in practice. METHODS: From 1993 to 2005, 218 neonates (mean age, 16 days; weight, 3,386 g) from seven European university hospitals were enrolled in a retrospective study. The surgical indications for laparoscopy (n = 204) and thoracoscopy (n = 14) were congenital abnormalities or exploratory procedures. RESULTS: Of the 16 surgical incidents that occurred (7.5%), mainly before 2001, 11 were minor (parietal hematoma, eventration). Three neonates had repeat surgery for incomplete treatment of pyloric stenosis. In two cases, the incidents were more threatening (duodenal wound, diaphragmatic artery injury), but without further consequences. No mortality is reported. The 26 anesthetic incidents (12%) that occurred during insufflation included desaturation (<80% despite 100% oxygen ventilation) (n = 8), transient hypotension requiring vascular expansion (n = 7), hypercapnia (>45 mmHg) (n = 5), hypothermia (<34.9 degrees C) (n = 4), and metabolic acidosis (n = 2). The insufflation had to be stopped in 7% of the cases (transiently in 9 cases, definitively in 6 cases). The significant risk factors for an incident (p < 0.05) were young age of the patient, low body temperature, thoracic insufflation, high pressure and flow of insufflation, and length of surgery. CONCLUSION: Despite advances in miniaturizing of instruments and growth in surgeons' experience, the morbidity of neonatal videosurgery is not negligible. A profile of the patient at risk for an insufflation-related incident emerged from this study and may help in the selection of neonates who will benefit most from these techniques in conditions of maximal safety.

An early thoracoscopic approach in necrotizing pneumonia in children: a report of three cases.

INTRODUCTION: Cavitary necrosis remains a rare complication of bacterial pneumonia in children. Conservative medical treatment and radical surgical treatment with lung resection are the current therapeutic choices. Evaluation of thoracoscopy for this pathology has not yet been reported. We describe 3 cases. MATERIALS AND METHODS: Between January 2001 and January 2002, 3 children (1, 2, and 3 years old) were admitted to our institution with necrotizing pneumonia. The diagnosis was based on injected computed tomography (CT) scan showing pulmonary condensation, intra-parenchymal bullae, and hypovascularization. In addition to an adapted antibiotic therapy, a thoracoscopic approach was decided on within 24 hours of diagnosis, with extensive decortication, ablation of superficial necrotic debris, irrigation, and drainage. RESULTS: No conversion to open thoracotomy or lung resection was needed. Admission to the intensive care unit was unnecessary. On average, apyrexia was reached on postoperative day (POD) 2 and tube drainage was removed on POD 15. Mean follow-up at 16 months showed excellent lung re-expansion with no relapse. CONCLUSION: On the condition that the decision is made quickly, thoracoscopy may be a valuable treatment option in childhood necrotizing pneumonia, as it hastens recovery and avoids lung resection. Injected CT scan allows an early diagnosis and we propose the first 24 hours after diagnosis as the optimal period for thoracoscopy because of the rapid natural course of lung gangrene.

Prenatal intrarenal neuroblastoma mimicking a mesoblastic nephroma: a case report.

Mesoblastic nephroma is by far the most frequent intrarenal fetal tumor. To the best of our knowledge, we report the first case of a newborn with an intrarenal neuroblastoma that was discovered prenatally. An intrarenal echogenic and homogenous mass was observed on routine prenatal ultrasonography, corroborated by magnetic resonance imaging, in a 30-week gestation fetus. A male weighing 3280 g was born with elevated blood pressure and cardiac failure. Postnatal ultrasound confirmed a left intrarenal tumor with microcalcifications and perirenal adenopathy. An open total left nephrectomy by laparotomy was performed. The pathologic study reported that the mass was an intrarenal neuroblastoma with local and regional invasion. Immediate postoperative urine analysis revealed a high level of vanillylmandelic acid, and blood samples showed high levels of normetanephrine. The purpose of this report is to demonstrate that prenatal intrarenal neuroblastoma can clinically and radiologically mimick a mesoblastic nephroma. High blood pressure, calcifications, and lymphadenopathy on ultrasound should raise the index of suspicion for a possible malignant process. Preoperative measurement of urinary vanillylmandelic acid (VMA) and metanephrines should be performed if the diagnosis is in doubt.

Laparoscopic redo fundoplication in children: failure causes and feasibility.

PURPOSE: This retrospective study reports our experience in laparoscopic approach after failure of antireflux surgery. It evaluates the results and circumstances of failure of the initial procedure to understand indications of refundoplication. METHODS: Four hundred seventeen patients were operated on for a gastroesophageal reflux disease (GERD) by laparoscopy in our unit from August 1993 to February 2005. Thirty redo procedures (7.19%) were performed. The indications were 24 (80%) recurrent reflux resistant to the medical treatment and 6 (20%) severe dysphagia resistant to iterative dilatations. The average age was 57.6 months. Nineteen patients (63%) were males and 11 patients (37%) were females. The time between the first and the redo procedure was an average of 16 months. Ten (33%) of them were neurologically impaired (NI); in 7 patients, a percutaneus gastrostomy was also associated. The techniques previously used were 13 Nissen, 7 Nissen-Rossetti, and 10 Toupet. RESULTS: The redo procedure was performed by laparoscopy in 27 cases. A conversion was necessary in 3 children because of a difficult dissection. In the 24 cases of recurrent reflux, we realized a valve disassembly, reconstruction of hiatus and Nissen refundoplication. In 3 cases of dysphagia, the release of the hiatus needed a complete valve redo. The mean operative time was 140 minutes (110 to 240 minutes). The sole complication was a pleural perforation. All patients were fed on the first day. The mean duration of hospitalization was 3.1 days. The follow-up was from 48 months to 12 years. A new recurrent reflux occurred in 6 patients; 5 of them were NI. CONCLUSION: The failure rate of the antireflux laparoscopic surgery is similar to the conventional surgery. The redo procedure is possible by laparoscopic with a success rate similar to the open redo surgery. The rate and morbidity of complications are acceptable and decrease with experienced surgeons. The indications of redo procedures should be similar to conventional surgery.

Thoracoscopy in pediatric pleural empyema: a prospective study of prognostic factors.

PURPOSE: The indications for thoracoscopy remain imprecise in cases of pleural empyema. This study aimed to identify preoperative prognostic factors to help in the surgical decision. METHODS: From 1996 to 2004, 50 children with parapneumonic pleural empyema underwent thoracoscopy either as the initial procedure (n = 26) or after failure of medical treatment (n = 24). Using multivariate analysis, we tested the prognostic value of clinical and bacteriological data, the ultrasonographic staging of empyema, and the delay before surgery. Outcome measures were technical difficulties, postoperative complications, time to apyrexia, duration of drainage, and length of hospitalization. RESULTS: The clinical and bacterial data did not significantly predict the postoperative course. Echogenicity and the presence of pleural loculations at ultrasonography were not independent significant prognostic factors. A delay between diagnosis and surgery of more than 4 days was significantly correlated (P < .05) with more frequent surgical difficulties, longer operative time, more postoperative fever, longer drainage time, longer hospitalization, and more postoperative complications, such as bronchopleural fistula, empyema relapse, and persistent atelectasia. CONCLUSION: The main prognostic factor for thoracoscopic treatment of pleural empyema is the interval between diagnosis and surgery. A 4-day limit, corresponding to the natural process of empyema organization, is significant. The assessment of loculations by ultrasonography alone is not sufficient to predict the postoperative course.

Tolerance of laparoscopy and thoracoscopy in neonates.

OBJECTIVES: Video-surgery in neonates is recent. Data on the respiratory, hemodynamic, and thermic effects during the first month of life are still sparse. This study aimed to evaluate the tolerance of video-surgery in neonates and to determine the risk factors of per-operative complications. METHODS: From 1994 to 2004, 49 neonates (mean age: 11 days; weight: 3285 g) underwent 50 video-surgical procedures. Indications for laparoscopy were duodenal atresias, volvulus with malrotation, pyloric stenosis, gastroesophageal reflux, cystic lymphangiomas, ovarian cysts, biliary atresia, and congenital diaphragmatic hernias; indications for thoracoscopy were esophageal atresias and tracheoesophageal fistula. RESULTS: Median operative time was 79 minutes. Mean insufflation pressure was 6.7 mm Hg (range: 3-13). Oxygen saturation decreased, especially with thoracic insufflation or high-pressure pneumoperitoneum. Systolic arterial pressure, which decreased in 20% of the patients, was controlled easily with vascular expansion. Thermic loss (mean postoperative temperature: 35.6 degrees C) was proportional to the duration of insufflation. No surgical incident was noted. Ten anesthetic incidents occurred (20%), 3 of which required temporary or definitive interruption of insufflation (O2 saturation <70%). Risk factors for an incident were low preoperative temperature, high variation of end-tidal pressure of CO2, surgical time >100 minutes, thoracic insufflation, and a high oxygen or vascular expansion requirement at the beginning of insufflation. CONCLUSION: The neonate's high sensitivity to insufflation is an important limiting factor of video-surgery. The described profile of the neonate at risk may help to reduce the frequency of adverse effects of this technique and improve its tolerance.