Yves Heloury

Laparoscopic adrenalectomy in children

BackgroundThe aim of this study was to describe the indications and results of laparoscopic adrenalectomy in children.MethodsThis retrospective multicenter study included six children (four boys, two girls) aged 2–16 years (mean, 9.5). Three children had hypertension. In three cases, the adrenal mass was discovered incidentally. The tumors were bilateral in two children right-sided in two cases, and left-sided in two cases. The mean tumor size was 4 cm (range, 1–7). Each child underwent MIBG scintigraphy and MRI before the operation.ResultsFour right and two left adrenal glands were resected by laparoscopy (transperitoneal), and two left glands were resected by retroperitoneoscopy. Two conversions were necessary for two left adrenal glands (on retroperitoneoscopy, one laparoscopy). Two partial resections and six adrenalectomies were performed. Histological examination of the tumors revealed two ganglioneuromas, one neuroblastoma, and five pheochromocytomas (two bilateral). One child had an involved node (pheochromocytoma). Both bilateral pheochromocytomas had von Hippel-Lindau disease. There was no morbidity. Mean hospitalstay was 6 days. Postoperative evaluation at 1 month was normal in all children.ConclusionThe indications for laparoscopic adrenalectomy in children are benign tumors and pheochromocytomas. In these cases, laparoscopic adrenalectomy is feasible and safe, even in cases of pheochromocytoma.

Familial acampomelic form of campomelic dysplasia caused by a 960 kb deletion upstream of SOX9

Campomelic dysplasia (CD) is a rare autosomal dominant osteochondrodysplasia with or without XY disorders of sexual development (DSD). Campomelia is absent in about 10% of the cases, referred to as the acampomelic form of CD (ACD). Most CDs are caused by mutations within the SOX9 coding region. Several CD patients with balanced chromosome rearrangements involving the 17q24 region have been reported suggesting the presence of cis‐regulatory elements upstream and/or downstream of the gene. Deletions upstream of SOX9 represent a third mechanism of mutation. To date, a 1.5 Mb de novo deletion in the SOX9 upstream region has been identified in a single 46,XY patient with ACD and DSD. We report here for the first time on a familial ACD caused by an inherited deletion mapping upstream of the SOX9 gene. Using high‐density oligoarray comparative genomic hybridization (CGH), we showed that the size of the deletion was 960 kb in the XY‐DSD child and her mother, both affected. The deletion lying from 517 kb to 1.477 Mb upstream of SOX9 remove several highly conserved elements and reduce the minimum critical size and therefore the number of highly conserved sequence elements responsible for ACD.

Disorders of sex development: Insights from targeted gene sequencing of a large international patient cohort

BackgroundDisorders of sex development (DSD) are congenital conditions in which chromosomal, gonadal, or phenotypic sex is atypical. Clinical management of DSD is often difficult and currently only 13% of patients receive an accurate clinical genetic diagnosis. To address this we have developed a massively parallel sequencing targeted DSD gene panel which allows us to sequence all 64 known diagnostic DSD genes and candidate genes simultaneously.ResultsWe analyzed DNA from the largest reported international cohort of patients with DSD (278 patients with 46,XY DSD and 48 with 46,XX DSD). Our targeted gene panel compares favorably with other sequencing platforms. We found a total of 28 diagnostic genes that are implicated in DSD, highlighting the genetic spectrum of this disorder. Sequencing revealed 93 previously unreported DSD gene variants. Overall, we identified a likely genetic diagnosis in 43% of patients with 46,XY DSD. In patients with 46,XY disorders of androgen synthesis and action the genetic diagnosis rate reached 60%. Surprisingly, little difference in diagnostic rate was observed between singletons and trios. In many cases our findings are informative as to the likely cause of the DSD, which will facilitate clinical management.ConclusionsOur massively parallel sequencing targeted DSD gene panel represents an economical means of improving the genetic diagnostic capability for patients affected by DSD. Implementation of this panel in a large cohort of patients has expanded our understanding of the underlying genetic etiology of DSD. The inclusion of research candidate genes also provides an invaluable resource for future identification of novel genes.

Retroperitoneal Laparoscopic Heminephrectomy in Duplex Kidney in Infants and Children: A 15-Year Experience

BACKGROUND Laparoscopic retroperitoneal partial nephrectomy in children remains a complex technique with limited diffusion among the paediatric surgical community. OBJECTIVE To report our experience with laparoscopic heminephrectomy in duplex kidneys after a 15-yr practise of the technique in children and infants. DESIGN, SETTING, PARTICIPANTS Forty-eight children with retroperitoneal laparoscopic partial nephrectomy (36 upper-pole nephrectomies [UPN] and 12 lower-pole nephrectomies [LPN]) were retrospectively included in this single-institution study. Median age at surgery was 8.6 mo (range 1.5-89), with a policy of early surgical intervention for UPN in cases involving a massively dilated upper tract. INTERVENTION Retroperitoneal laparoscopic partial nephrectomy for duplex kidney in lateral position (n=31) and prone in the last 17 cases. MEASUREMENTS We assessed intraoperative and postoperative morbidity. Follow-up (median 14 mo, range 6-125 mo) was based on clinical review and renal ultrasound. RESULTS AND LIMITATIONS Median duration of surgery was 120 min (range 71-215). Ten procedures (21%) were converted into open surgery, mostly at the beginning of the experience (eight during the first 20 cases, as compared to one conversion in the last 20). Among four converted LPNs, three were converted for difficulties during parenchymal section. Six UPN were converted for difficulties of exposure, with a strong correlation with age: all six were infants, with a median age of 3.25 mo (range 1.5-8 mo). We observed one case (case 4) of functional loss of the remaining lower moiety. CONCLUSIONS This study shows a high conversion rate during the learning curve for laparoscopic heminephrectomy. Retroperitoneoscopic UPN remains a challenging procedure in children, especially in small infants with very dilated collecting systems. The possibility of vascular damage to the remaining moiety warrants a very cautious dissection of the renal pedicle and should lead to conversion when clear visualization of vascular anatomy is not ascertained.

Multicentric assessment of the safety of neonatal videosurgery

BackgroundComplex 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.MethodsFrom 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.ResultsOf 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°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.ConclusionDespite 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.

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.

The Genetic and Environmental Factors Underlying Hypospadias

Hypospadias results from a failure of urethral closure in the male phallus and affects 1 in 200-300 boys. It is thought to be due to a combination of genetic and environmental factors. The development of the penis progresses in 2 stages: an initial hormone-independent phase and a secondary hormone-dependent phase. Here, we review the molecular pathways that contribute to each of these stages, drawing on studies from both human and mouse models. Hypospadias can occur when normal development of the phallus is disrupted, and we provide evidence that mutations in genes underlying this developmental process are causative. Finally, we discuss the environmental factors that may contribute to hypospadias and their potential immediate and transgenerational epigenetic impacts.

Laparoscopic nissen fundoplication with simultaneous percutaneous endoscopic gastrostomy in children.

AbstractBackground: The aim of the study was to evaluate the results of laparoscopic Nissen fundoplication (LNF) with simultaneous percutaneous endoscopic gastrostomy (PEG) in children with gastroesophageal reflux (GER) disease documented by upper gastrointestinal contrast and/or pH monitoring and/or esophageal endoscopy. Methods: Fifteen LNF + PEGs were performed in children with pathologic antecedents: ten neurologically impaired children, two ORL (otorhinolaryngeal) pathologies. Two cases of AIDS, and one neuroblastoma. In one case, disruption of the fundoplication occurred during insufflation of the stomach. The child was reoperated on the 3rd day using an open procedure, so she was excluded from the results of the LNF. Results: Two children had postoperative complications: one with cardiac insufficiency, one case of dehydration. Fourteen LNFs were controlled at 3 months by gastroesophageal X-ray and pH-metry. The 14 gastroesophageal X-rays were normal in 12 cases; gastroesophageal reflux was present in two cases. Twelve pH monitorings were analyzed (two technical failures), the median time pH<4 was 0.2% (0–20). Only one pH monitoring was pathologic (pH<4: 20%). This recurrent reflux to led to a second LNF with a good clinical result. Conclusions: In conclusion, it is possible to perform LNF and PEG during the same operative procedure. Short-term results are satisfactory with 14% recurrent GER. Long-term results need to be evaluated.

Hereditary pancreatitis in children: surgical implications with special regard to genetic background.

PURPOSE Hereditary pancreatitis (HP) is the primary etiology of chronic pancreatitis during childhood, progressing through recurrent episodes of acute pancreatitis and finally leading to pancreatic insufficiencies. Hereditary pancreatitis is because of mutations of the cationic trypsinogen (PRSS1) gene. Some other genes, such as SPINK1 or CFTR, have been associated with familial idiopathic chronic pancreatitis. The aim of our study was to clearly define diagnostic and therapeutic strategies for HP patients, through an analysis of our study group and a review of the literature. METHODS All children admitted from 1995 to 2007 with a final diagnosis of hereditary pancreatitis were restrospectively included in the study. We analyzed all medical records with special attention given to cases involving genetic screening (PRSS1, SPINK1, and CFTR genes). RESULTS Ten children were included. Eight had HP with PRSS1 mutation, 2 of them without a familial history of chronic pancreatitis. The 2 others patients had SPINK1 mutations. Three HP patients were operated on for acute complications of pancreatitis and are well with a mean follow-up of 5.5 years. No patient had pancreatic insufficiencies or weight loss. CONCLUSIONS Hereditary pancreatitis is associated with severe pancreatitis, with a greater risk of developing pancreatic cancer. It must therefore be diagnosed correctly and treated to prevent its considerable complications.

Severe bladder dysfunction revealed prenatally or during infancy

OBJECTIVE Although thought to be an acquired condition, non-neurogenic neurogenic bladder may sometimes be a congenital dysfunction, revealed before toilet training. We report our experience with the condition diagnosed prenatally or during early infancy. PATIENTS AND METHOD We retrospectively reviewed cases of severe bladder dysfunction with upper-tract impairment, without neurological or obstructive pathology, in children diagnosed before toilet training: five with prenatal diagnosis of severe hydro-ureteronephrosis (group 1) and six with signs of bladder dysfunction during infancy (group 2). RESULTS Follow up of group 1 showed decompensation toward severe bladder dysfunction, diagnosed after either toilet training or ureteral reimplantation (n=3). After a median follow up of 14 years (0.5-20), four were on clean intermittent catheterization with bladder augmentation and one required sphincteric re-education with good result. Two of the five had chronic renal failure. In group 2, six children (two females) presented at median age of 20 months (2-30) with indirect signs of bladder dysfunction, including vesicoureteral reflux (n=4) and/or hydro-ureteronephrosis (n=4). After a median follow up of 11 years (5-20), three were on clean intermittent catheterization (two Mitrofanoff channels), and three underwent bladder augmentation. Three children had chronic renal failure of whom one underwent renal transplant. CONCLUSION These cases of severe bladder dysfunction were initially misdiagnosed. In both groups, follow up revealed severe dilatation of the upper tract and secondary renal impairment. Antenatal diagnosis of bilateral pyeloureteral dilatation may be the first sign of early bladder dysfunction.