Sabine Sarnacki

Outcome of Suprarenal Localized Masses Diagnosed during the Perinatal Period

The growing use of abdominal ultrasonography during pregnancy and in the postnatal period is leading to the discovery of an increasing number of suprarenal masses. The optimal diagnosis and treatment of these masses has not yet been determined.

Thoracoscopic Treatment of Mediastinal Cysts in Children

BACKGROUND/PURPOSE The development of thoracoscopic surgery has made many procedures possible, including the treatment of mediastinal cysts in children. The authors report their experience with this procedure between 1992 and 1997. METHODS Surgery was performed on 22 children aged from 1 month to 9 years (median, 27 months), weighing 5 to 49 kg (median, 12.5 kg). Diagnosis was made by antenatal ultrasound scan in six cases (27%), with a chest x-ray performed for respiratory symptoms in 14 cases, and with a chest x-ray performed for positive tuberculin intradermoreaction in two cases. Decision to resect the cyst was determined by thoracoscopy in 21 of the 22 cases, and by open surgery in one case only (subcarinal compressive cyst with left lung distension and a mediastinal shift). RESULTS Eighteen of the 21 (86%) cases were treated successfully by thoracoscopy. In three cases of bronchogenic cysts, we performed an associated thoracotomy because the dissection was too difficult and dangerous. In three cases, a small part of a common wall between the cyst and the bronchus was not removed. The pathological diagnosis was bronchogenic cysts in 15 cases (71%), pleuropericardiat cysts in three cases (14%), esophageal duplication in two cases (10%), and cystic hygroma in one case (5%). Two postoperative complications were observed: one esophageal wound and a case of recurrent pneumothorax after chest tube removal. Patients were discharged after 2 to 11 days (median, 3 days). Follow-up was uneventful. CONCLUSIONS Treatment of mediastinal cyst by thoracoscopy is feasible in most cases. Compressive cysts with lung distension and mediastinal shift remain a contraindication. If the cysts have a common wall with the bronchus or esophagus, or if they are subcarinal, the dissection may be difficult and dangerous, and thoracotomy may be preferable.

An overview of isolated and syndromic oesophageal atresia.

Oesophageal atresia (OA) and/or tracheo‐oesophageal fistula (TOF) are frequent malformations observed in approximately one in 3500 births. OA/TOF can be divided clinically into isolated OA (IOA) and syndromic OA (SOA) when associated with other features, the most frequent being cardiac, limb and vertebral malformations or anal atresia. SOA is observed in 50% of patients and can be subdivided into several causative groups comprising environmental agents, chromosomal disorders, malformative associations (CHARGE syndrome and VATER/VACTERL association), and other multiple congenital anomaly disorders. The observation of chromosomal disorders with SOA, as well as mouse models of OA provide support for the involvement of genetic factors in OA. Yet, epidemiological data (twin and family studies) do not support the major role of genetic factors in the majority of cases of IOA but rather a multifactorial model. However, several genes involved in SOA have been recently identified, namely N‐MYC, SOX2, and CHD7 involved in Feingold (MIM 164280), anophthalmia‐oesophageal‐genital (MIM 600992) and CHARGE syndromes respectively (MIM 214800), suggesting that OA/TOF, at least in their syndromic forms, may be a highly genetically heterogeneous group.

EFTUD2 haploinsufficiency leads to syndromic oesophageal atresia

Background: Oesophageal atresia (OA) and mandibulofacial dysostosis (MFD) are two congenital malformations for which the molecular bases of syndromic forms are being identified at a rapid rate. In particular, the EFTUD2 gene encoding a protein of the spliceosome complex has been found mutated in patients with MFD and microcephaly (MIM610536). Until now, no syndrome featuring both MFD and OA has been clearly delineated. Results: We report on 10 cases presenting with MFD, eight of whom had OA, either due to de novo 17q21.31 deletions encompassing EFTUD2 and neighbouring genes or de novo heterozygous EFTUD2 loss-of-function mutations. No EFTUD2 deletions or mutations were found in a series of patients with isolated OA or isolated oculoauriculovertebral spectrum (OAVS). Conclusions: These data exclude a contiguous gene syndrome for the association of MFD and OA, broaden the spectrum of clinical features ascribed to EFTUD2 haploinsufficiency, define a novel syndromic OA entity, and emphasise the necessity of mRNA maturation through the spliceosome complex for global growth and within specific regions of the embryo during development. Importantly, the majority of patients reported here with EFTUD2 lesions were previously diagnosed with Feingold or CHARGE syndromes or presented with OAVS plus OA, highlighting the variability of expression and the wide range of differential diagnoses.

Opsoclonus-myoclonus in children associated or not with neuroblastoma.

OBJECTIVE To compare the clinical data at diagnosis, treatment and neurological outcome in 34 children with opsoclonus-myoclonus syndrome (OMS) associated with a detected neuroblastoma or not. STUDY DESIGN This is a multicentric retrospective study of 34 children presenting with OMS from four pediatric centers diagnosed between 1988 and 2008. RESULTS Twenty-two patients had OMS associated with a neuroblastoma. These patients all had neuroblastomas with favourable prognostic features; all underwent surgery, six received chemotherapy. Twelve children had OMS without a detected neuroblastoma. For OMS, the main treatment in all children was corticotherapy (n=33), but immunoglobulins (n=13), cyclophosphamide (n=4) and rituximab (n=4) were also given. In the 27 OMS patients with or without neuroblastoma whose follow up was greater than two years, the neurological outcome was evaluated: 59.3% had neurological sequelae, including motor, praxic and/or language sequelae (n=9), persistent ataxia (n=6) and moderate motor deficit (n=3). No significant difference in neurological outcome was noted between the two patient groups. CONCLUSION Our retrospective study provides further evidence that OMS with or without a detected neuroblastoma is the same disease, whose major challenges are the neurological sequelae. An international collaboration is required to improve the knowledge about OMS, the treatment and the outcome in this rare disorder.

Ovarian transposition in prepubescent and adolescent girls with cancer

Ovarian transposition was the first procedure proposed to preserve fertility in girls with cancer and is indicated for patients with tumours requiring pelvic radiation at doses of 42·0-58·4 Gy, much higher doses than those that can induce loss of ovarian function (4-20 Gy). Ovarian transposition is usually done after neoadjuvant chemotherapy and is completed by minimally invasive surgery or open surgery in case of concomitant resection of the abdominal tumour. According to the type of tumour, the ovaries are moved and placed in the paracolic gutters when the radiation field reaches the midline (for medulloblastoma or urogenital rhabdomyosarcoma), contralaterally to the tumour (for pelvic sarcomas), or in line with the iliac crests (for Hodgkins lymphoma). However, in 10-14% of cases the procedure can fail to protect the ovaries. Although few long-term results in adults are available, normal hormonal function and pregnancies have been reported in a few long-term follow-up studies. In view of the continued development of fertility preservation techniques, ovarian transposition should be discussed at a multidisciplinary meeting at the time of cancer diagnosis.

WNT/β-catenin pathway activation in Wilms tumors: A unifying mechanism with multiple entries?

Based on characterization of both genomic and expression status of WT1 and CTNNB1 (β‐catenin) in a series of 60 Wilms tumor samples, combined with genome‐wide expression profiling of these tumors, normal mature and fetal kidney controls, we show that WT1/β‐catenin expression was a better classifier than WT1/CTNNB1 mutations. We present molecular data supporting that the WNT pathway is involved in both tumor classes, with and without WT1/β‐catenin alterations. In the tumor class with WT1/β‐catenin alterations, we identified overexpression of 14 previously unreported WNT target genes, including TWIST1. We show that the TWIST1 protein was specifically expressed in these tumors, where staining was restricted to the stromal, nuclear β‐catenin positive, component. By comparing the state of the WNT pathway in tumors without WT1/β‐catenin alterations and fetal kidneys we provide evidence that suggests that these tumors have a heightened level of pathway activation. We characterized mutations of the WNT pathway regulator gene WTX in 16% of this tumor class. Moreover, genome‐transcriptome correlation analysis allowed us to identify three other WNT pathway regulator genes that could participate in the activation of the WNT pathway: BCL9 (1p36.2), CTNNBIP1 (1p36.2), and CBY1 (22q13.1). These genes thus represent new potential important actors in WT tumorigenesis.

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.

Wandering spleen in children: multicenter retrospective study

Wandering spleen in children is a rare condition. The diagnosis is difficult, and any delay can cause splenic ischemia. An epidemiologic, semiological, and surgical diagnosis questionnaire on incidence of wandering spleen in children was sent to several French surgical teams. We report the results of this multicenter retrospective study. Fourteen cases (6 girls, 8 boys) were reported between 1984 and 2009; the age range varies between 1-day-old and 15 years; 86% were seen in the emergency department. Ninety-three percent had diffuse abdominal pain. For 57% of the cases, it was their first symptomatic episode of this type. No diagnosis was established based on the clinical results alone. All patients had presurgical imaging diagnosis. Open surgery was performed on 64% cases. Forty-three had splenectomy for splenic ischemia. Thirty-six percent had splenopexy, 14% had laparoscopic gastropexy, and 7% had spleen repositioning and regeneration. Complications were noted in 60% of the cases resulting in postsplenopexy splenic ischemia. Early diagnosis and surgery are the best guarantee for spleen preservation. Even if the choice of one technique, splenopexy or gastropexy, can be argued, gastropexy has the advantage of avoiding splenic manipulation and restoring proper physiologic anatomy. When there is no history of abdominal surgery, laparoscopy surgery seems the best procedure.

Bacteriologic epidemiology and empirical treatment of pediatric complicated appendicitis

Preoperative samples in the context of complicated appendicitis (CA) are rarely collected, and there is no consensus regarding the optimal antibiotic therapy in children. To help optimize empirical preoperative treatment, we studied clinical and bacteriologic data from a prospective cohort of 93 children with CA in a French hospital. All the bacteria isolated from peritoneal fluids were identified, using phenotypic and/or molecular techniques. The most commonly recovered species were Escherichia coli (71%), Streptococcus group milleri (34%), anaerobes (20%), and Pseudomonas aeruginosa (19%). The association piperacillin-tazobactam is an accurate choice of empirical therapy as it is active against 97% of bacteria. A third-generation cephalosporin with metronidazole in association with an aminoglycoside is a good alternative. Although antibiotic use may be considered as an adjunct to surgical intervention of CA, the appropriate use of preoperative antibiotics is essential and must be constantly reevaluated according to the bacterial epidemiology.