Pascal de Lagausie

Effect of Amnioinfusion on the Outcome of Prenatally Diagnosed Gastroschisis

Objective: Following recent data showing that an inflammatory response exists in the amniotic fluid of gastroschisis-affected fetuses, we hypothesized that amniotic fluid exchange or amnioinfusion would improve the prognosis of prenatally diagnosed gastroschisis. Methods: We compared the outcome of prenatally amnioinfused fetuses with gastroschisis to non-amnioinfused fetuses with gastroschisis. 10 patients undergoing this procedure were matched with 10 patients of our previous study. Comparisons were done on data including surgical procedure, follow-up in the NICU and the gastro-pediatric unit. Results: Our results show that gastroschisis-affected fetuses undergoing amnioinfusion had a lower duration of curarization after surgery (2.2 ± 1.9 vs. 6.8 ± 6.9 days, p = 0.019), a shorter delay before full oral feeding (49.7 ± 21.5 vs. 72.3 ± 56.6 days, NS), and a shorter overall length of hospitalization (59.5 ± 19.7 vs. 88.5 ± 73.6 days, NS). We confirmed our previous data showing that amniotic fluid displays a chronic inflammation profile. Conclusion: Our data suggest that amnioinfusion could improve the outcome of gastroschisis affected fetuses. The hypothesis by which this improvement could be due to a reduction of an inflammatory response remains to be proved.

Calretinin immunohistochemistry: a simple and efficient tool to diagnose Hirschsprung disease

Diagnosis of Hirschsprung disease (HD) is quite entirely based on the histopathological analysis of suction rectal biopsies. This hematoxylin and eosin approach has some limitations, despite the help of acetylcholinesterase staining. The aim of this study was to assess the diagnostic value of calretinin immunochemistry as a simple and reliable method in the diagnosis of HD. A total of 131 initial rectal biopsies carried out for suspicion of HD in children were retrieved, and calretinin immunohistochemistry was carried out on paraffin-embedded biopsies. Diagnosis of HD was made when no staining was observed. The results were statistically analyzed in comparison with our standard method (histology and acetylcholinesterase staining). 130 biopsies were accurately diagnosed on the basis of the positivity or negativity of calretinin staining. The senior pathologists diagnosed all cases of HD with no false positives. Furthermore, 12 additional cases initially considered as doubtful for HD using the standard method, were accurately diagnosed using calretinin immunohistochemistry. The false negative was a case of HD with a calretinin-positive biopsy. We also demonstrate the ease of calretinin interpretation compared with acetylcholinesterase for the junior pathologist. Calretinin immunohistochemistry overcomes most of the difficulties encountered using the combination of histology and acetylcholinesterase staining, and detects almost all cases of HD with confidence, with no false positives. Thus, we demonstrate that calretinin is superior to acetylcholinesterase to complete histology and could advantageously substitute for acetylcholinesterase.

Endothelin receptor expression in human lungs of newborns with congenital diaphragmatic hernia

Congenital diaphragmatic hernia (CDH) is a major cause of refractory respiratory failure in the neonatal period and is characterized by persistent pulmonary hypertension of the newborn (PPHN) and pulmonary hypoplasia. Endothelin‐1 (ET‐1) dysregulation may play a significant role in the pathophysiology of PPHN and ET‐1 acts through binding to type A (ETA) and type B (ETB) receptors. Therefore, ETA and ETB receptor protein expression was studied using immunohistochemistry in 10 lung specimens obtained from newborns with CDH, and 4 normal lung specimens, in order to explore whether dysregulation of ETA and ETB expression contributes to PPHN. ETA and ETB mRNAs were then quantified using real‐time RT‐PCR in laser‐microdissected pulmonary resistive arteries. In the lungs of newborns with CDH, immunohistochemistry of both ETA and ETB receptors demonstrated over‐expression in the thickened media of pulmonary arteries. Using laser microdissection and real‐time RT‐PCR, higher levels of ETA and ETB mRNA were found in CDH pulmonary arteries than in controls: this increase was more pronounced for ETA mRNA. This study provides the first demonstration of ET‐1 receptor dysregulation in association with structural alteration of pulmonary arteries in newborns with CDH and PPHN. This dysregulation preferentially affects the ETA receptor. These results suggest that dysregulation of ET‐1 receptors may contribute to PPHN associated with CDH. Copyright

Laparoscopic Partial Splenectomy: Indications and results of a multicenter retrospective study

IntroductionPartial splenectomy (PS) in children is a surgical option in haematological diseases and focal splenic tumours. The aim of this study was to describe the feasibility and the results of laparoscopic partial splenectomy in children in these two indications by a multicentric retrospective study.MethodsThe authors reviewed the files of all children who underwent laparoscopic PS between March 2002 and September 2006 in two paediatric surgical centers. The data of 11 children were collected and included clinical presentation, age, gender, radiographic examinations, surgical procedure, need for blood transfusion and early complications.ResultsFrom March 2002 to September 2006, laparoscopic PS had been performed on 11 children (6 boys, 5 girls) aged 23 months to 11 years (mean 7, 9). Four children had splenic focal tumours and seven had haematological diseases: six hereditary spherocytosis (HS) and one hemoglobinosis E. During the surgical procedure for haematological diseases 75–80% of the splenic tissue was removed. When PS was performed for focal splenic tumours, the splenic remnant was around 70%. No preoperative complications occurred (no bleeding, no diaphragmatic injury). Neither preoperative nor conversion was necessary. One postoperative complication occurred (left pleural effusion) but required no further treatment. The mean hospital stay was 7.7 days (range from 3 days to 10 days). No infectious postoperative complications occurred; the mean follow up was 21.1 months (range 3–52 months).ConclusionLaparoscopic partial splenectomy is feasible and safe in children with hypersplenism or focal splenic tumours. Partial splenectomy is a good way to prevent postsplenectomy infections by preservation of the immune role of spleen in children with haematological diseases. This technique performed for focal splenic tumours allows the surgeon to choose the size of the splenic remnant.

Amniotic fluid inflammatory proteins and digestive compounds profile in fetuses with gastroschisis undergoing amnioexchange

Objective  In gastroschisis, an inflammatory process related to the presence of digestive compounds may be involved in intestinal damage. We measured the amniotic fluid concentrations of total protein, ferritin and amylase, lipase, γ‐glutamyl transferase and bile acids before each amnioexchange performed in women whose infants had gastroschisis. We estimated the correlation among total proteins, ferritin and digestive compounds and postnatal outcome.

Laparoscopic resection of abdominal neuroblastoma.

BackgroundSince indications for laparoscopic adrenalectomy have progressively expanded to pediatric surgery, preliminary reports have studied the laparoscopic approach for abdominal neuroblastoma (NB). We aimed to report on the indications and the results of laparoscopic resection in a large series of abdominal NBs.MethodsA retrospective multicenter study included 45 children with abdominal NBs (28 localized, 11 stage 4, 6 stage 4s) and laparoscopic resection of their abdominal primary tumor. Primary site of the tumor was the adrenal gland in 41 cases and retroperitoneal space in 4. The median age at surgery was 12 months (1–122); median tumor size was 37 mm (12–70). Resection was performed through transperitoneal laparoscopy (n = 38) or retroperitoneoscopy (n = 7).ResultsComplete macroscopic resection was achieved in 43 of 45 children (96%). The median duration of pneumoperitoneum was 70 min (30–160), and the length of hospital stay was 3 days (2–9). Four procedures (9%) were converted to open surgery, and tumor rupture occurred in three cases. Of the 28 children with localized disease, there was a 96% overall survival (OS) rate after a median follow-up of 28 months (4–94). There was one local relapse in this subgroup, with subsequent complete remission. For the entire 45-children cohort, four children died and three presented a recurrence resulting in OS, disease-free survival, and event-free survival rates of 84% ± 8.1, 84% ± 8.2, and 77% ± 9.1 respectively.ConclusionLaparoscopic resection of abdominal primary allows effective local control of the disease in a wide range of clinical situations of neuroblastoma, with an acceptable morbidity.

Biochemical investigations of bowel inflammation in gastroschisis.

Neonates with gastroschisis have perivisceritis resulting from contact between the bowel and amniotic fluid. Here, we characterized the mediators involved in this inflammatory process in humans and ewes, to find a reliable marker of this process. We have diagnosed 41 cases of gastroschisis since 1995. Amniotic fluid sampled for karyotyping between 15 and 32 wk of gestation was also used to assay cytokines and inflammatory proteins. The findings were compared with those in 93 age-matched controls. Amniotic fluid cells were analyzed by means of cytology. Histologic examination of the bowel was performed when neonatal appendectomy was performed. The findings were compared with those obtained in a ewe model of gastroschisis. In gastroschisis, amniotic total protein, IL-6, IL-8, and ferritin levels were significantly higher than in controls. Gastroschisis was associated with significantly higher cell counts (mainly mononuclear cells) in amniotic fluid. At birth, macrophages were abundant in the fibrous peel covering the bowel. Similar results were obtained in the ewe model. Gastroschisis may be associated with a subchronic inflammatory process of variable intensity. This inflammation is restricted to the bowel wall and involves inflammatory cells such as macrophages, which may secrete ferritin, neopterin, and calprotectin.

Endoscopic Injection With Polydimethylsiloxane for the Treatment of Pediatric Urinary Incontinence in the Neurogenic Bladder: Long-Term Results

PURPOSE We report the long-term results of endoscopic injection of PDMS in correcting urinary incontinence in children with neurogenic bladder. MATERIALS AND METHODS We performed a single center, retrospective study of patients receiving endoscopic injections of PDMS. All procedures were performed as outpatient surgery using endoscopic guidance. Procedure tolerance was assessed at 15 days, and efficacy was evaluated at 3 months, 6 months and annually thereafter. Success was defined as periods of dryness between bladder voiding of more than 4 hours during the daytime without the need to wear pads. Improvement was defined as periods of dryness greater than 2 and less than 4 hours with occasional protection. RESULTS A total of 49 children (21 boys and 28 girls) have received 1 or more injections of PDMS since 1995. Etiology was spina bifida in 41 patients (84%), with surgery (enterocystoplasty and/or bladder neck reconstruction) performed previously in 27 patients. Mean patient age was 14 years (standard deviation 4.8). Mean volume of PDMS per treatment was 3.6 ml. At the end of the 6-year mean followup 16 patients (33%) were continent and 7 (14%) were improved. Continence was unchanged in the remaining 26 patients (53%). After a significant deterioration of the results the outcome remained almost unchanged from 18 months of followup. Bladder neck surgery, bladder hyperactivity if medically controlled and gender have no influence statistically on the long-term results. CONCLUSIONS Injection of PDMS for incontinence of neurogenic origin is a reliable technique that achieves long-term continence in almost a third of the patients. This procedure can be used either as first line treatment or in addition to other surgical techniques. The initial success of the procedure seems predictive of success in the long term, and results are stable after 18 months of followup.

Mediastinal pancreatic pseudocyst in a child

: Mediastinal pancreatic pseudocyst is a rare occurrence in children and may be difficult to diagnose. Internal drainage via a cystenterostomy and a simple external drainage are two of the treatment options that are currently employed. We describe the case of an 11-year-old boy with a mediastinal pseudocyst who was treated via a thoracoscopic approach using an original pulmonary exclusion. The pseudocyst disappeared in 15 days and there has been no recurrence. No adjuvant treatment was necessary. Endoscopic retrograde cholangiopancreatography (ERCP) was useful in establishing the etiology (pancreas divisum). We believe that the thoracoscopic approach is a reproducible, simple, and safe procedure for the treatment of mediastinal pseudocysts. The technique may represent a valid alternative to cystogastrostomy.

Gene transfection into fetal sheep airways in utero using guanidinium-cholesterol cationic lipids

Over the last several years, we have developed a novel class of cationic lipids, cholesterol derivatives characterized by polar head groups with guanidinium functions. We have in particular shown that bis(guanidinium)‐tren‐cholesterol/dioleoylphosphatidylethanolamine (BGTC/DOPE) cationic liposomes can mediate efficient gene transfection into the mouse airways in vivo via direct intratracheal administration or intranasal instillation. As prenatal gene therapy may be necessary for the treatment of a variety of congenital lung diseases, we have explored in the present work the feasibility of BGTC‐mediated gene transfection into the respiratory tract of fetal sheep in utero.