Publications by authors named "Yves Aigrain"

59 Publications

Feasibility and safety of magnetic-end double-J ureteral stent insertion and removal in children.

World J Urol 2020 Jul 4. Epub 2020 Jul 4.

Service de Chirurgie Viscérale et Urologie Pédiatriques, APHP, Hôpital Necker, Paris, France.

Purpose: The need for surgical removal of a double-J ureteral stent (DJUS) is considered one of its disadvantages. Apart from increased cost, repeated exposure to general anesthesia is a concern in children. Alternative techniques have been described, all failing to become integrated into mainstream practice. Stents with a distal magnetic end, although introduced in the early 1980s, have only recently gained acceptance. We report the feasibility and safety of insertion and removal of a magnetic-end double-J ureteral stent (MEDJUS) in a pediatric population.

Materials And Methods: We retrospectively analyzed the use of the Magnetic Black-Star Urotech MEDJUS between 11/2016 and 12/2019 in children. Stents were removed in the outpatient clinic using a transurethral catheter with a magnetic tip.

Results: MEDJUS insertion was attempted in 100 patients (65 boys). Mean age was 7.8 years (0.5-18). The stent was placed in an antegrade procedure (n = 47), by a retrograde route (n = 10), and during open surgery (n = 43). Stent insertion was successful in 84 cases (84%). All 16 failures occurred during the antegrade approach in laparoscopic pyeloplasty, with inability to push the stent and its magnet through the ureterovesical junction in 14. Magnetic removal was attempted in 83 patients, successful in 81 (98%). There was no added morbidity with the MEDJUS.

Conclusions: The use of MEDJUS is a safe and effective strategy that obviates the need for additional general anesthesia in children. Its insertion is similar to that with regular DJUS, and its easy and less time-consuming removal benefits both the patient and the hospital and validates its clinical use.
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http://dx.doi.org/10.1007/s00345-020-03339-0DOI Listing
July 2020

The use of fetal MRI for renal and urogenital tract anomalies.

Prenat Diagn 2020 01 4;40(1):100-109. Epub 2019 Dec 4.

Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes and Fetus & LUMIERE team, Paris, France.

Fetal anomalies are detected in approximately 2% of all fetuses and, among these, genitourinary tract abnormalities account for 30% to 50% of all structural anomalies present at birth. Although ultrasound remains the first line diagnostic modality, fetal MRI provides important additional structural and functional information, especially with the development of faster sequences and the use of functional sequences. The added value of MRI-based imaging is three-fold: (a) improvement of diagnostic accuracy by adequate morphological examination, (b) detection of additional anomalies, and (c) in addition, MRI has the potential to provide information regarding renal function. In this review, we describe the role of fetal MRI in the anatomical evaluation of renal and urogenital tract anomalies, and we also touch upon the contribution of functional MRI to the diagnostic workup of these conditions.
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http://dx.doi.org/10.1002/pd.5610DOI Listing
January 2020

Long-term outcome of methylmalonic aciduria after kidney, liver, or combined liver-kidney transplantation: The French experience.

J Inherit Metab Dis 2020 03 11;43(2):234-243. Epub 2020 Feb 11.

Reference Center of Pediatric Nephrology, Hôpital Universitaire Necker-Enfants Malades, APHP, Filière ORKID, ERKnet, University Paris Descartes, Paris, France.

Organ transplantation is discussed in methylmalonic aciduria (MMA) for renal failure, and poor quality of life and neurological outcome. We retrospectively evaluated 23 French MMA patients after kidney (KT), liver-kidney (LKT), and liver transplantation (LT). Two patients died, one after LKT, one of hepatoblastoma after KT. One graft was lost early after KT. Of 18 evaluable patients, 12 previously on dialysis, 8 underwent KT (mean 12.5 years), 8 LKT (mean 7 years), and 2 LT (7 and 2.5 years). At a median follow-up of 7.3 (KT), 2.3 (LKT), and 1.0 years (LT), no metabolic decompensation occurred except in 1 KT. Plasma and urine MMA levels dramatically decreased, more after LKT. Protein intake was increased more significantly after LKT than KT. Enteral nutrition was stopped in 7/8 LKT, 1/8 KT. Early complications were frequent after LKT. Neurological disorders occurred in four LKT, reversible in one. Five years after KT, four patients had renal failure. The metabolic outcomes were much better after LKT than KT. LKT in MMA is difficult but improves the quality of life. KT will be rarely indicated. We need more long-term data to indicate early LT, in the hope to delay renal failure and prevent neurodevelopmental complications.
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http://dx.doi.org/10.1002/jimd.12174DOI Listing
March 2020

Retroperitoneal Approach for Ureteropelvic Junction Obstruction: Encouraging Preliminary Results With Robot-Assisted Laparoscopic Repair.

Front Pediatr 2019 28;7:209. Epub 2019 May 28.

Service de Chirurgie Viscérale et Urologie Pédiatriques, APHP, Hôpital Necker, Paris, France.

Robot-assisted laparoscopic pyeloplasty (RALP) is gaining acceptance among pediatric urologists. Few studies have evaluated the retroperitoneal approach for RALP. We share our experience from the first 2 years of a multidisciplinary pediatric robotic program in our center. We performed a retrospective analysis of prospectively collected data of children undergoing RALP for ureteropelvic junction obstruction ( = 50). Diagnosis was confirmed by ultrasound and Tc-99m mercaptoacetyltriglycine renal scan or MRI; the same criteria were used to evaluate outcome. Surgical approach was chosen according to a specific algorithm. Transperitoneal approach ( = 13) was reserved for horseshoe kidney, ectopic kidney, and redo surgery. We analyzed the 37 cases performed by a lateral retroperitoneal approach. Dismembered pyeloplasty was done for all cases and anastomosis was performed using a running monofilament 6/0 absorbable suture. All were drained by double J stent. Patient data, operating room parameters and postoperative course were recorded. The median age was 7.9 years (5.1-13.8); the youngest was 2 years old. The median weight was 23 kg (17-41) with the smallest weighing 12.4 kg. Aberrant crossing vessels were present in 18 children. Median set-up time, from skin incision until the end of the 4-port insertion, was 33 min (29-48). Median surgeon's console time was 151 min (136-182). No conversion to an open procedure was necessary. The postoperative course was free of complications, except urinary tract infection in 6 children. All but 4 patients were discharged on day one. Median follow-up was 9 months (5-13). Redo pyeloplasty was not required. Practical training of other colleagues was possible after 10 cases performed by the same surgeon. These preliminary results suggest that retroperitoneal RALP in children is feasible, safe and effective. It is an excellent option with ideal anatomical exposure. Longer term results as well as continued practice will identify and overcome any challenges and enable surgical mastery of this procedure which is still evolving.
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http://dx.doi.org/10.3389/fped.2019.00209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547808PMC
May 2019

Surgery is not superior to dilation for the management of vaginal agenesis in Mayer-Rokitansky-Küster-Hauser syndrome: a multicenter comparative observational study in 131 patients.

Am J Obstet Gynecol 2018 09 21;219(3):281.e1-281.e9. Epub 2018 Jul 21.

Department of Pediatric Endocrinology, Gynecology, and Diabetology, Assistance Publique - Hôpitaux de Paris, Hôpital Necker, Paris, France; Université Paris Descartes, Paris, France.

Background: Vaginal agenesis in Mayer-Rokitansky-Küster-Hauser syndrome can be managed either by various surgeries or dilation. The choice still depends on surgeon's preferences rather than on quality comparative studies and validated protocols.

Objective: We sought to compare dilation and surgical management of vaginal agenesis in Mayer-Rokitansky-Küster-Hauser syndrome, in terms of quality of life, anatomical results, and complications in a large multicenter population.

Study Design: Our multicenter study included 131 patients >18 years, at least 1 year after completing vaginal agenesis management. All had an independent gynecological evaluation including a standardized pelvic exam, and completed the World Health Organization Quality of Life instrument (general quality of life) as well as the Female Sexual Function Index and Female Sexual Distress Scale-Revised (sexual quality of life) scales. Groups were: surgery (N = 84), dilation therapy (N = 26), and intercourse (N = 20). One patient was secondarily excluded because of incomplete surgical data. For statistics, data were compared using analysis of variance, Student, Kruskal-Wallis, Wilcoxon, and Student exact test.

Results: Mean age was 26.5 ± 5.5 years at inclusion. In all groups, World Health Organization Quality of Life scores were not different between patients and the general population except for lower psychosocial health and social relationship scores (which were not different between groups). Global Female Sexual Function Index scores were significantly lower in the surgery and dilation therapy groups (median 26 range [2.8-34.8] and 24.7 [2.6-34.4], respectively) than the intercourse group (30.2 [7.8-34.8], P = .044), which had a higher score only in the satisfaction dimension (P = .004). However, the scores in the other dimensions of Female Sexual Function Index were not different between groups. The Female Sexual Distress Scale-Revised median scores were, respectively, 17 [0-52], 20 [0-47], and 10 [10-40] in the surgery, dilation therapy, and intercourse groups (P = .38), with sexual distress in 71% of patients. Median vaginal depth was shorter in dilatation therapy group (9.6 cm [5.5-12]) compared to surgery group (11 cm [6-15]) and intercourse group (11 cm [6-12.5]) (P = .039), but remained within normal ranges. One bias in the surgery group was the high number of sigmoid vaginoplasties (57/84, 68%), but no differences were observed between surgeries. Only 4 patients achieved vaginas <6.5 cm. Delay between management and first intercourse was 6 months (not significant). Seventy patients (53%) had dyspareunia (not significant), and 17 patients all from the surgery group had an abnormal pelvic exam. In the surgery group, 34 patients (40.5%) had complications, requiring 20 secondary surgeries in 17 patients, and 35 (42%) needed postoperative dilation. In the dilation therapy group, 13 (50%) needed maintenance dilation.

Conclusion: Surgery is not superior to therapeutic or intercourse dilation, bears complications, and should therefore be only a second-line treatment. Psychological counseling is mandatory at diagnosis and during therapeutic management.
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http://dx.doi.org/10.1016/j.ajog.2018.07.015DOI Listing
September 2018

Low-Cost Training Simulator for Open Dismembered Pyeloplasty: Development and Face Validation.

J Surg Educ 2018 Jan - Feb;75(1):188-194. Epub 2017 Aug 1.

Department of Pediatric Surgery, Hôpital Necker-Enfants Malades, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, France; INSERM U1151, Institut Necker Enfants Malades, Hôpital Necker-Enfants Malades, Paris, France.

Purpose: Surgical simulation has benefited from a surge in interest over the last decade because of the increasing need for a change in the traditional apprenticeship model of teaching surgery. Open surgery for ureteropelvic junction (UPJ) poses unique training challenges owing to smaller workspaces, and finer sutures used that require increased surgical dexterity when compared with adult analogues. We describe the development and face validation of a low-cost training simulator for open dismembered pyeloplasty.

Materials And Methods: The simulator is built with A4 Kraft envelopes, catheter tip syringe filled with 30mL of air, tape, 260 modeling balloon, and 11-in party balloon. Evaluation of the device is based on an evaluation form including 11 items on a 5-point Likert-type scale. Thirty-one departments of pediatric surgery in France were contacted and received a pack containing 4 to 10 devices, already set up and ready for use, a tutorial and an evaluation form. Candidates were stratified according to their level of expertise.

Results: A total of 180 devices were sent. Procedures on the device were performed 118 times (65%) by expert surgeons (n = 44), fellows (n = 25), and residents (n = 49). Statistically significant difference was noted for 4 items (anatomy, model exposition, UPJ resection, and difficulty) for the 3 levels of expertise. The global score evaluation for realistic items, face validity, and usability was 4.2 (range: 1-5).

Conclusion: This low-cost model is evaluated as an efficient tool for UPJ teaching and training. It shows promise as an educational tool.
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http://dx.doi.org/10.1016/j.jsurg.2017.06.010DOI Listing
November 2018

Segmental volvulus in the neonate: A particular clinical entity.

J Pediatr Surg 2017 Mar 13;52(3):454-457. Epub 2016 Oct 13.

AP-HP, Hôpital Necker-Enfants malades, Service de Chirurgie Pédiatrique Viscérale, Paris, France; Université Paris Descartes, Paris, France.

Background: Complete intestinal volvulus is mainly related to congenital anomalies of the so-called intestinal malrotation, whereas segmental volvulus appears as a distinct entity, mostly observed during the perinatal period. Because these two situations are still lumped together, the aim of this study was to describe the particular condition of neonatal segmental volvulus.

Study Design: We analyzed the circumstances of diagnosis and management of 17 consecutives neonates operated for segmental volvulus more than a 10-year period in a single institution. During the same period, 19 cases of neonatal complete midgut volvulus were operated.

Results: Prenatal US exam anomalies were observed in 16/17 (94%) of segmental volvulus, significantly more frequently than in complete volvulus (p=0.003). Intestinal malposition was described peroperatively in all cases of complete volvulus, but also in 4/17 segmental volvulus (23%). Intestinal resection was performed in 88% of segmental volvulus when only one extensive intestinal necrosis was observed in complete volvulus. Parenteral nutrition was required in all patients with segmental volvulus with a median duration of 50days (range 5-251).

Conclusion: Segmental volvulus occurs mainly prenatally and leads to fetal ultrasound anomalies. This situation, despite a limited length of intestinal loss, is associated to significant postnatal morbidity.

Type Of The Study: Treatment study.

Level Of Evidence: Level IV.
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http://dx.doi.org/10.1016/j.jpedsurg.2016.10.002DOI Listing
March 2017

Efficacy and Safety of Continuous Subcutaneous Infusion of Recombinant Human Gonadotropins for Congenital Micropenis during Early Infancy
.

Horm Res Paediatr 2017 12;87(2):103-110. Epub 2017 Jan 12.

Background: Early postnatal administration of gonadotropins to infants with congenital hypogonadotropic hypogonadism (CHH) can mimic minipuberty, thereby increasing penile growth. We assessed the effects of gonadotropin infusion on stretched penile length (SPL) and hormone levels in infants with congenital micropenis.

Methods: Single-center study including 6 males with micropenis in case of isolated CHH (n = 4), panhypopituitarism (n = 1), and partial androgen insensitivity syndrome (PAIS; n = 1). Patients were evaluated at baseline, monthly and at the end of the study through a clinical examination (SPL, testicular position and size), serum hormone assays (testosterone, luteinizing hormone, follicle-stimulating hormone, inhibin B, anti-Müllerian hormone [AMH]), and ultrasound of penis/testes.

Results: In CHH, significant increases occurred in serum testosterone (from undetectable level to 3.5 ± 4.06 ng/mL [12.15 ± 14.09 nmol/L]), SPL (from 13.8 ± 4.5 to 42.6 ± 5 mm; p < 0.0001), inhibin B (from 94.8 ± 74.9 to 469.4 ± 282.5 pg/mL, p = 0.04), and AMH (from 49.6 ± 30.6 to 142 ± 76.5 ng/mL, p = 0.03). Micropenis was corrected in all patients, except one. On treatment, in the patient with PAIS, SPL was increased from 13 to 38 mm.

Conclusions: Early gonadotropin infusion is a safe, well-tolerated and effective treatment. The effect in PAIS has not been reported previously. Long-term follow-up is needed to assess the impact, if any, on future fertility and reproduction.
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http://dx.doi.org/10.1159/000454861DOI Listing
June 2017

Twenty-eight years of intestinal transplantation in Paris: experience of the oldest European center.

Transpl Int 2017 Feb;30(2):178-186

Pediatric Surgery, Necker-Enfants malades Hospital, Paris, France.

Our aim was to describe our achievements in pediatric intestinal transplantation (ITx) and define areas for improvement. After a period (1987-1990) of nine isolated small bowel transplants (SBTx) where only one patient survived with her graft, 110 ITx were performed on 101 children from 1994 to 2014: 60 SBTx, 45 liver-small bowel, four multivisceral (three with kidneys), and one modified multivisceral. Indications were short bowel syndrome (36), motility disorders (30), congenital enteropathies (34), and others (1). Induction treatment was introduced in 2000. Patient/graft survival with a liver-containing graft or SBTx was, respectively, 60/41% and 46/11% at 18 years. Recently, graft survival at 5/10 years was 44% and 31% for liver-containing graft and 57% and 44% for SBTx. Late graft loss occurred in 13 patients, and 7 of 10 retransplanted patients died. The main causes of death and graft loss were sepsis and rejection. Among the 55 currently living patients, 21 had a liver-containing graft, 19 a SBTx (17 after induction), and 15 were on parenteral nutrition. ITx remains a difficult procedure, and retransplantation even more so. Over the long term, graft loss was due to rejection, over-immunosuppression was not a significant problem. Multicenter studies on immunosuppression and microbiota are urgently needed.
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http://dx.doi.org/10.1111/tri.12894DOI Listing
February 2017

Preoperative risk factors for intra-operative bleeding in pediatric liver transplantation.

Pediatr Transplant 2016 Dec 29;20(8):1065-1071. Epub 2016 Sep 29.

Pediatric surgery unit, Hôpital Necker enfants malades, Paris, France.

This study analyzes the preoperative risk factors for intra-operative bleeding in our recent series of pediatric LTs. Between November 2009 and November 2014, 84 consecutive isolated pediatric LTs were performed in 81 children. Potential preoperative predictive factors for bleeding, amount of intra-operative transfusions, postoperative course, and outcome were recorded. Cutoff point for intra-operative HBL was defined as intra-operative RBC transfusions ≥1 TBV. Twenty-six patients (31%) had intra-operative HBL. One-year patient survival after LT was 66.7% (CI 95%=[50.2-88.5]) in HBL patients and 83.8% (CI 95%=[74.6-94.1]) in the others (P=.054). Among 13 potential preoperative risk factors, three of them were identified as independent predictors of high intra-operative bleeding: abdominal surgical procedure(s) prior to LT, factor V level ≤30% before transplantation, and ex situ parenchymal transsection of the liver graft. Based on these findings, we propose a simple score to predict the individual hemorrhagic risk related to each patient and graft association. This score may help to better anticipate intra-operative bleeding and improve patient's management.
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http://dx.doi.org/10.1111/petr.12794DOI Listing
December 2016

Spontaneous bladder rupture in non-augmented bladder exstrophy.

J Pediatr Urol 2016 Dec 16;12(6):400.e1-400.e5. Epub 2016 Jul 16.

Department of Paediatric Urology, Royal Children's Hospital, Flemington Road, Parkville, VIC, Australia.

Objective: Bladder perforation is not commonly described in bladder exstrophy patients without bladder augmentation. The goal of this study was to identify the risk factors of spontaneous perforation in non-augmented exstrophy bladders.

Methods: The study was a retrospective multi-institutional review of bladder perforation in seven male and two female patients with classic bladder exstrophy-epispadias (E-E).

Results: Correction of E-E was performed using Kelly repair in two and staged repair in seven (Table). Bladder neck repair was performed in eight patients at a mean age of 6 years. Three patients had additional urethral surgery. Before rupture, six patients were voiding only per urethra. Two patients were voiding urethrally but were also performing occasional CIC via a Mitrofanoff. One patient was performing CIC 3 hourly per urethra. Six were dry during the day. Six of the patients had lower urinary tract symptoms: five had frequency and four were straining to void. Two had suffered episodes of urinary retention. Pre-rupture ultrasound showed that the upper urinary tract was dilated in four patients. Micturating cystourethrogram was performed in six showing vesico-ureteral reflux in five. Two had urethral stenosis. Nuclear medicine was done in three patients with two abnormal differential function. Urodynamics was performed in two patients with low capacity (100 mL) and hypocompliant (<10) bladders. Both had high leak point pressures: 60 cmHO at 100 mL. The mean age at rupture was 11 years, with a range of 5-20 years. Patients presented with abdominal pain, associated with signs of intestinal obstruction in seven and fever in two. Eight patients underwent laparotomy and one prolonged drainage via SPC. Simple closure was performed in seven and bladder neck closure in one, because of extension of the rupture inferiorly. All patients recovered well. Following rupture, five underwent augmentation and Mitrofanoff. One of these suffered a recurrent rupture. Two other patients refused augmentation and Mitrofanoff and one of these has since had a subsequent rupture.

Conclusions: The limitations of this series include the small number of patients and its retrospective nature, without knowledge of the incidence. Bladder rupture is a risk even in non-augmented bladder exstrophy. It is potentially life-threatening and most often requires laparotomy. Rupture occurs because of poor bladder emptying and/or high pressure. Urodynamics may identify those at risk. CIC with or without augmentation should not be delayed once poor bladder emptying and/or high pressure are identified.
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http://dx.doi.org/10.1016/j.jpurol.2016.04.054DOI Listing
December 2016

Outcome of home parenteral nutrition in 251 children over a 14-y period: report of a single center.

Am J Clin Nutr 2016 05 30;103(5):1327-36. Epub 2016 Mar 30.

Departments of Pediatric Gastroenterology, Hepatology and Nutrition, Paris Descartes University, Paris, France; and.

Background: Parenteral nutrition (PN) is the main treatment for intestinal failure.

Objective: We aimed to review the indications for home parenteral nutrition (HPN) in children and describe the outcome over a 14-y period from a single center.

Design: We conducted a retrospective study that included all children who were referred to our institution and discharged while receiving HPN between 1 January 2000 and 31 December 2013. The indications for HPN were divided into primary digestive diseases (PDDs) and primary nondigestive diseases (PNDDs). We compared our results to a previous study that was performed in our unit from 1980 to 2000 and included 302 patients.

Results: A total of 251 patients were included: 217 (86%) had a PDD. The mean ± SD age at HPN onset was 0.7 ± 0.3 y, with a mean duration of 1.9 ± 0.4 y. The indications for HPN were short bowel syndrome (SBS) (59%), PNDD (14%), congenital enteropathies (10%), chronic intestinal pseudo-obstruction syndromes (9%), inflammatory bowel diseases (5%), and other digestive diseases (3%). By 31 December 2013, 52% of children were weaned off of HPN, 9% of the PDD subgroup had intestinal transplantation, and 10% died mostly because of immune deficiency. The major complications of HPN were catheter-related bloodstream infections (CRBSIs) (1.7/1000 d of PN) and intestinal failure-associated liver disease (IFALD) (51 children; 20% of cohort). An increased rate of CRBSIs was observed compared with our previous study, but we saw a decreasing trend since 2012. No noteworthy deceleration of growth was observed in SBS children 6 mo after weaning off HPN.

Conclusions: SBS was the major indication for HPN in our cohort. IFALD and CRBSIs were potentially life-threatening problems. Nevertheless, complication rates were low, and deaths resulted mostly from the underlying disease.
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http://dx.doi.org/10.3945/ajcn.115.121756DOI Listing
May 2016

Comparative results of gastric banding in adolescents and young adults.

J Pediatr Surg 2016 Jul 28;51(7):1122-5. Epub 2016 Feb 28.

AP-HP, Hôpital Necker-Enfants malades, Service de Chirurgie Pédiatrique Viscérale, Paris, France; Université Paris Descartes, Paris, France. Electronic address:

Background/purpose: Obesity has become a major public health priority. Because of disappointing results obtained with dietary and medical programs, bariatric surgery has been offered to adolescents, although this practice remains controversial. Our aim was to evaluate laparoscopic adjustable gastric banding (LAGB) in adolescents at 2-year follow-up.

Material And Methods: This prospective study, from 2008 to 2013, compared results between adolescent patients and young adult controls. The LAGB technique and the follow-up program were similar. Weight loss and comorbid disease were analyzed.

Results: Thirty-six adolescents (mean age at surgery=16.7±1.3years) were operated on and compared to 53 young adults (mean age at surgery=21.7±1.9years). The mean weight and BMI at surgery were 124.4±20.7 and 43.9±5.5kg/m(2), respectively. Among the adolescents, none were diabetic or hypertensive. The mean glycated hemoglobin was 5.6±1.2%. In four cases (11%) dyslipidemia was observed. There was no significant difference between the two groups in terms of initial preoperative weight or BMI. The absolute BMI values at 6, 12 and 24months after surgery were comparable between adolescents and young adults: 38.7 vs 39.8, 36.0 vs 37.6 and 33.5 vs 36.1kg/m(2), respectively. The excess weight loss was higher in adolescents at 12 and 24months: 48.6 vs 37.6% (p=0.03); and 62.3 vs 45.5% (p=0.02). During this period, insulin resistance and dyslipidemia decreased similarly in both groups.

Conclusion: Provided there is careful selection of patients and a supportive multidisciplinary team, satisfying results can be obtained after LAGB in adolescents, comparable to those obtained in young adults at 2-year follow-up.
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http://dx.doi.org/10.1016/j.jpedsurg.2016.02.043DOI Listing
July 2016

Primordial Influence of Post-operative Compliance on Weight Loss After Adolescent Laparoscopic Adjustable Gastric Banding.

Obes Surg 2016 Jan;26(1):98-104

AP-HP, Hôpital Necker-Enfants Malades, Service de Chirurgie Pédiatrique Viscérale, 149 rue de Sevres, 75015, Paris, France.

Background: Accumulating evidence suggests that the benefits seen in adult bariatric surgery can be reproduced in adolescents. In contrast with North America, bariatric surgery in adolescents is still not well accepted in Europe and indications and protocols have still to be formulated.

Methods: This prospective study tested the gastric banding procedure in 49 patients operated in a single French institution since 2008. The mean age at surgery was 16.2 ± 0.9 years with a weight of 118.8 ± 22.3 kg and body mass index of 42.5 ± 5.9 kg/m(2).

Results: At 6, 12 and 24 months after surgery, weight was 103.7 ± 20.8 kg, 98.7 ± 21 kg and 93.6 ± 19.3 kg, respectively (p < 0.001), corresponding to excess weight loss (EWL) of 31.6 ± 17.2 %, 41.8 ± 21.4 % and 59.1 ± 24.9 % (p < 0.001), respectively. Multivariate analysis showed that the number of consultations per year was the only variable significantly associated to weight loss. Metabolic disorders were corrected, with a decreased prevalence of insulin resistance from 100 to 17 % and normalisation of homeostasis model assessment-insulin resistance (HOMA-IR) at 24 months (2.09 ± 0.95). Band-related complications were five slippages, one psychological intolerance and two ports repositioning. Six patients (12 %) had the device explanted. The death of a patient was an exceptionally severe adverse event.

Conclusion: Given frequent follow-up support by a multidisciplinary team, laparoscopic adjustable gastric banding (LAGB) surgery in adolescent results in sustained weight loss. However, even exceptional, potentially serious complications are possible and long-term follow-up is needed to evaluate the risk/benefit ratio at 5 or 10 years after LAGB surgery.
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http://dx.doi.org/10.1007/s11695-015-1725-4DOI Listing
January 2016

Strengths and limitations of using fluorine-fluorodihydroxyphenylalanine PET/CT for congenital hyperinsulinism.

Expert Rev Endocrinol Metab 2014 Sep 13;9(5):477-485. Epub 2014 Aug 13.

b Centre de référence des maladies héréditaires du métabolisme de l'enfant, et l'adulte, AP-HP Hôpital Necker-Enfants Malades, Université Paris Descartes, Paris, France.

fluorine-fluorodihydroxyphenylalanine (FDOPA) PET/CT is currently the first-line imaging technique to distinguish between focal and diffuse forms of congenital hyperinsulinism (CHI) and to accurately localize focal forms. However, this technique has a number of limitations, mainly the very small size of focal forms or inversely a very large focal form mimicking a diffuse form, and misinterpretation of physiologic uptake masking hot spots or inversely mimicking focal forms. The other limitation is the limited availability of the radiopharmaceutical. FDOPA PET/CT has no recognized competitor to date among the available morphologic and functional imaging techniques. Other potential approaches using specific tracers for positron emission tomography (PET) are discussed, using radiopharmaceuticals specific for β cell mass or targeting somatostatin receptors. These radiopharmaceuticals can be labeled with gallium-68, a PET emitter readily available in PET centers equipped with 68Ge/68Ga generators.
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http://dx.doi.org/10.1586/17446651.2014.949240DOI Listing
September 2014

Impact of spinal dysraphism on urinary and faecal prognosis in 25 cases of cloacal malformation.

J Pediatr Urol 2014 Dec 19;10(6):1199-205. Epub 2014 Jul 19.

Department of Paediatric Surgery, Necker-Enfants Malades Hospital, APHP, Paris Descartes University, Paris, France; National Reference Centre for Rare Diseases on Anorectal Malformations and Rare Pelvic Anomalies (MAREP), Necker-Enfants Malades Hospital, APHP, Paris Descartes University, Paris, France.

Objective: Urinary and faecal continence are key challenges goal of cloacal malformation management. Most well-known prognostic factors are the length of common channel (CC) and the presence of a sacral defect, but the impact of associated spinal dysraphism is less well documented. The aim of this study was to investigate the impact of different types of dysraphism on urinary and faecal continence in this patient population.

Materials And Methods: From 1991 to 2011, charts and office notes of 25 patients with cloacal malformation were retrospectively reviewed. At last clinic visit, urinary and faecal continence status according to Krickenbeck criteria were correlated with the length of CC, the presence of a sacral defect (sacral ratio), and the presence of different types of spinal cord dysraphism using magnetic resonance imaging (MRI) and Fisher's exact test.

Results: Mean follow-up was 8 years (4 months-21 years). The sacral ratio was abnormal (below 0.74) in 18 cases out of 25 (72%). MRI review showed normal spinal cord in eight out of 23 cases (Group 1), spinal cord anomaly in 15 out of 23 cases (65%) including nine cases of tethered cord complex (Group 2) and six cases of a short spinal cord (Group 3). While statistical analysis showed a difference regarding urinary prognosis between the groups (p=0.005), no significant difference was found regarding faecal prognosis. None of the six patients with short spinal cord were continent for both urinary and faecal prognosis.

Conclusions: This is the first study, which highlights the impact of different types of spinal dysraphism on functional outcome in patients with cloaca. Short spinal cord seemed to carry the worst prognosis. A prospective study with a larger series is mandatory to confirm these preliminary results.
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http://dx.doi.org/10.1016/j.jpurol.2014.05.012DOI Listing
December 2014

Characterization of a novel CYP19A1 (aromatase) R192H mutation causing virilization of a 46,XX newborn, undervirilization of the 46,XY brother, but no virilization of the mother during pregnancies.

Mol Cell Endocrinol 2014 Jun 4;390(1-2):8-17. Epub 2014 Apr 4.

Pediatric Endocrinology and Diabetology, University Children's Hospital, Bern, Switzerland; Department of Clinical Research, University of Bern, Bern, Switzerland. Electronic address:

Background: P450 aromatase (CYP19A1) is essential for the biosynthesis of estrogens from androgen precursors. Mutations in the coding region of CYP19A1 lead to autosomal recessive aromatase deficiency. To date over 20 subjects have been reported with aromatase deficiency which may manifest during fetal life with maternal virilization and virilization of the external genitalia of a female fetus due to low aromatase activity in the steroid metabolizing fetal-placental unit and thus high androgen levels. During infancy, girls often have ovarian cysts and thereafter fail to enter puberty showing signs of variable degree of androgen excess. Moreover, impact on growth, skeletal maturation and other metabolic parameters is seen in both sexes.

Objective And Hypothesis: We found a novel homozygous CYP19A1 mutation in a 46,XX girl who was born at term to consanguineous parents. Although the mother did not virilize during pregnancy, the baby was found to have a complex genital anomaly at birth (enlarged genital tubercle, fusion of labioscrotal folds) with elevated androgens at birth, normalizing thereafter. Presence of 46,XX karyotype and female internal genital organs (uterus, vagina) together with biochemical findings and follow-up showing regression of clitoral hypertrophy, as well as elevated FSH suggested aromatase deficiency. Interestingly, her older brother presented with mild hypospadias and bilateral cryptorchidism and was found to carry the same homozygous CYP19A1 mutation. To confirm the clinical diagnosis, genetic, functional and computational studies were performed.

Methods And Results: Genetic analysis revealed a homozygous R192H mutation in the CYP19A1 gene. This novel mutation was characterized for its enzymatic activity (Km, Vmax) in a cell model and found to have markedly reduced catalytic activity when compared to wild-type aromatase; thus explaining the phenotype. Computational studies suggest that R192H disrupts the substrate access channel in CYP19A1 that may affect binding of substrates and exit of catalytic products.

Conclusion: R192H is a novel CYP19A1 mutation which causes a severe phenotype of aromatase deficiency in a 46,XX newborn and maybe hypospadias and cryptorchidism in a 46,XY, but no maternal androgen excess during pregnancy.
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http://dx.doi.org/10.1016/j.mce.2014.03.008DOI Listing
June 2014

Mouse muscle as an ectopic permissive site for human pancreatic development.

Diabetes 2013 Oct 8;62(10):3479-87. Epub 2013 Jul 8.

INSERM U845, Research Center Growth and Signalling, Faculté de Médecine Cochin, Université Paris Descartes, Paris, France.

While sporadic human genetic studies have permitted some comparisons between rodent and human pancreatic development, the lack of a robust experimental system has not permitted detailed examination of human pancreatic development. We previously developed a xenograft model of immature human fetal pancreas grafted under the kidney capsule of immune-incompetent mice, which allowed the development of human pancreatic β-cells. Here, we compared the development of human and murine fetal pancreatic grafts either under skeletal muscle epimysium or under the renal capsule. We demonstrated that human pancreatic β-cell development occurs more slowly (weeks) than murine pancreas (days) both by differentiation of pancreatic progenitors and by proliferation of developing β-cells. The superficial location of the skeletal muscle graft and its easier access permitted in vivo lentivirus-mediated gene transfer with a green fluorescent protein-labeled construct under control of the insulin or elastase gene promoter, which targeted β-cells and nonendocrine cells, respectively. This model of engraftment under the skeletal muscle epimysium is a new approach for longitudinal studies, which allows localized manipulation to determine the regulation of human pancreatic development.
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http://dx.doi.org/10.2337/db13-0554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3781474PMC
October 2013

Aortic bypass and bilateral renal autotransplantation for mid-aortic syndrome.

Pediatr Nephrol 2013 Sep 13;28(9):1871-4. Epub 2013 Apr 13.

Pediatric Surgery unit, Hôpital Necker-Enfants malades, 149 rue de Sèvres, 75015, Paris, France.

Background: Middle aortic syndrome (MAS) is a rare condition characterized by stenosis of the proximal abdominal aorta and the origin of the renal and digestive arteries. When medical therapy and interventional radiology fail to control threatening reno-vascular arterial hypertension (AHT), surgery is required and may need several interventions, which are usually delayed until late childhood.

Case: We report on a 3-year-old girl with severe AHT (180/130 mmHg) caused by MAS. There was no evidence of generalized vascular disease or complications of AHT. AHT failed to respond to medical therapy (five drugs), endovascular dilatation, and stenting was considered unfeasible due to the complex multiple strictures. Surgery consisted of: explantation of the two kidneys; aortic bypass between the lower thoracic and lower abdominal aorta using a prosthetic graft; reimplantation of the kidneys onto the normal iliac arteries. The post-operative course was uneventful. Owing to recurrent stenosis of the re-implanted renal arteries, endoluminal dilatations were performed 4 and 5 months after surgery. Two years after surgery, the child is alive and well, off anti-hypertensive therapy, with normal blood pressure.

Conclusion: Mild aortic syndrome can be treated with a one-stage surgical repair with aorto-aortic bypass and bilateral auto-transplantation, even in young children.
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http://dx.doi.org/10.1007/s00467-013-2475-yDOI Listing
September 2013

Cultural bias in the AAP's 2012 Technical Report and Policy Statement on male circumcision.

Pediatrics 2013 Apr 18;131(4):796-800. Epub 2013 Mar 18.

Department of Epidemiology Research, Statens Serum Institut, Copenhagen and Center for Sexology Research, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.

The American Academy of Pediatrics recently released its new Technical Report and Policy Statement on male circumcision, concluding that current evidence indicates that the health benefits of newborn male circumcision outweigh the risks. The technical report is based on the scrutiny of a large number of complex scientific articles. Therefore, while striving for objectivity, the conclusions drawn by the 8 task force members reflect what these individual physicians perceived as trustworthy evidence. Seen from the outside, cultural bias reflecting the normality of nontherapeutic male circumcision in the United States seems obvious, and the report's conclusions are different from those reached by physicians in other parts of the Western world, including Europe, Canada, and Australia. In this commentary, a different view is presented by non-US-based physicians and representatives of general medical associations and societies for pediatrics, pediatric surgery, and pediatric urology in Northern Europe. To these authors, only 1 of the arguments put forward by the American Academy of Pediatrics has some theoretical relevance in relation to infant male circumcision; namely, the possible protection against urinary tract infections in infant boys, which can easily be treated with antibiotics without tissue loss. The other claimed health benefits, including protection against HIV/AIDS, genital herpes, genital warts, and penile cancer, are questionable, weak, and likely to have little public health relevance in a Western context, and they do not represent compelling reasons for surgery before boys are old enough to decide for themselves.
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http://dx.doi.org/10.1542/peds.2012-2896DOI Listing
April 2013

Prenatal management of disorders of sex development.

J Pediatr Urol 2012 Dec 4;8(6):576-84. Epub 2012 Nov 4.

Clinical and Molecular Genetics Unit, UCL Institute of Child Health, London, UK.

Disorders of sex development (DSD) rarely present prenatally but, as they are very complex conditions, management should be directed by highly specialised medical teams to allow consideration of all aspects of diagnosis, treatment and ethical issues. In this brief review, we present an overview of the prenatal presentation and management of DSD, including the sonographic appearance of normal genitalia and methods of determining genetic sex, the prenatal management of pregnancies with the unexpected finding of genital ambiguity on prenatal ultrasound and a review of the prenatal management of pregnancies at high risk of DSD. As this is a rapidly developing field, management options will change over time, making the involvement of clinical geneticists, paediatric endocrinologists and urologists, as well as fetal medicine specialists, essential in the care of these complex pregnancies. The reader should also bear in mind that local social, ethical and legal aspects may also influence management.
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http://dx.doi.org/10.1016/j.jpurol.2012.10.012DOI Listing
December 2012

Congenital hyperinsulinism: current trends in diagnosis and therapy.

Orphanet J Rare Dis 2011 Oct 3;6:63. Epub 2011 Oct 3.

Centre de Référence des Maladies Héréditaires du Métabolisme de l'Enfant et l'Adulte, AP-HP Hôpital Necker-Enfants Malades, Université Paris Descartes, Paris, France.

Congenital hyperinsulinism (HI) is an inappropriate insulin secretion by the pancreatic β-cells secondary to various genetic disorders. The incidence is estimated at 1/50, 000 live births, but it may be as high as 1/2, 500 in countries with substantial consanguinity. Recurrent episodes of hyperinsulinemic hypoglycemia may expose to high risk of brain damage. Hypoglycemias are diagnosed because of seizures, a faint, or any other neurological symptom, in the neonatal period or later, usually within the first two years of life. After the neonatal period, the patient can present the typical clinical features of a hypoglycemia: pallor, sweat and tachycardia. HI is a heterogeneous disorder with two main clinically indistinguishable histopathological lesions: diffuse and focal. Atypical lesions are under characterization. Recessive ABCC8 mutations (encoding SUR1, subunit of a potassium channel) and, more rarely, recessive KCNJ11 (encoding Kir6.2, subunit of the same potassium channel) mutations, are responsible for most severe diazoxide-unresponsive HI. Focal HI, also diazoxide-unresponsive, is due to the combination of a paternally-inherited ABCC8 or KCNJ11 mutation and a paternal isodisomy of the 11p15 region, which is specific to the islets cells within the focal lesion. Genetics and 18F-fluoro-L-DOPA positron emission tomography (PET) help to diagnose diffuse or focal forms of HI. Hypoglycemias must be rapidly and intensively treated to prevent severe and irreversible brain damage. This includes a glucose load and/or a glucagon injection, at the time of hypoglycemia, to correct it. Then a treatment to prevent the recurrence of hypoglycemia must be set, which may include frequent and glucose-enriched feeding, diazoxide and octreotide. When medical and dietary therapies are ineffective, or when a focal HI is suspected, surgical treatment is required. Focal HI may be definitively cured when the partial pancreatectomy removes the whole lesion. By contrast, the long-term outcome of diffuse HI after subtotal pancreatectomy is characterized by a high risk of diabetes, but the time of its onset is hardly predictable.
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http://dx.doi.org/10.1186/1750-1172-6-63DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3199232PMC
October 2011

Testicular function and physical outcome in young adult males diagnosed with idiopathic 46 XY disorders of sex development during childhood.

Eur J Endocrinol 2011 Dec 30;165(6):907-15. Epub 2011 Sep 30.

Pediatric Surgery and Urology Department, Centre de Référence Maladies Endocriniennes Rares de la Croissance, Hôpital Robert Debré Assistance Publique-Hôpitaux de Paris and Univ Paris Diderot, Sorbonne Paris Cité, Paris, France.

Objective: There are few studies of outcome in male patients with undefined 46 XY disorder of sex development (DSD). We aimed to assess testicular function and clinical characteristics after puberty in men with idiopathic 46 XY DSD. Design We conducted a University Hospital-based observational follow-up study.

Methods: Nineteen patients with severe hypospadias associated with other signs of defective virilization, such as microphallus, cryptorchidism, and/or bifid scrotum, who were initially managed during childhood between 1988 and 1994, were evaluated at a median age of 17.6 (16.3; 17.8) years. Outcome measures included clinical findings and serum testosterone, FSH, LH, and inhibin B concentrations.

Results: Testicular function was normal in only five (26%) patients. Impaired testicular function was observed in 14 (74%) patients and was partial (n=6; 32%) or total (n=8; 42%), requiring testosterone treatment for the initial (n=2) or secondary (n=6) induction of puberty. Undescended testis (unilateral n=3, bilateral n=2) was found and surgically managed only in the 14 patients with testicular impairment. Testosterone treatment in early childhood greatly increased penis length in all patients, but persistent microphallus following surgical treatment was observed at the end of puberty in most patients, with no difference between patients with and without testicular dysfunction (penis length of 68 (60; 75) vs 65 (60; 65) mm; P=0.42). Half the patients presented an adult height more than 5 cm below their target height.

Conclusion: Men diagnosed with idiopathic 46 XY DSD during childhood are at high risk of testicular insufficiency and persistent micropenis, and this should be taken into account during the follow-up.
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http://dx.doi.org/10.1530/EJE-11-0588DOI Listing
December 2011

Nitric oxide activity through guanylate cyclase and phosphodiesterase modulation is impaired in fetal lambs with congenital diaphragmatic hernia.

J Pediatr Surg 2011 Aug;46(8):1516-22

Department of Pediatric Surgery, Robert Debré Hospital, Assistance Publique-Hôpitaux de Paris, Sérurier, 75019 Paris, France.

Background: Congenital diaphragmatic hernia (CDH) is associated with pulmonary hypertension and death. Administration of nitric oxide (NO) alone remains ineffective in CDH cases. We investigated in near full-term lambs with and without CDH the role of guanylate cyclase (GC), the enzyme activated by NO in increasing cyclic 3'-5'-guanylosine monophosphate, and the role of phosphodiesterase (PDE) 5, the enzyme-degrading cyclic 3'-5'-guanylosine monophosphate.

Methods: Congenital diaphragmatic hernia was surgically created in fetal lambs at 85 days of gestation. Pulmonary hemodynamics were assessed by means of pressure and blood flow catheters (135 days). In vitro, we tested drugs on rings of isolated pulmonary vessels.

Results: In vivo, sodium nitroprusside, a direct NO donor, and methyl-2(4-aminophenyl)-1,2-dihydro-1-oxo-7-(2-pyridinylmethoxy)-4-(3,4,5 trimethoxyphenyl)-3-isoquinoline carboxylate sulfate (T-1032) and Zaprinast, both PDE 5 blockers, reduced pulmonary vascular resistance in CDH and non-CDH animals. The activation of GC by sodium nitroprusside and the inhibition of PDE 5 by T-1032 were less effective in CDH animals. In vitro, the stimulation of GC by 3(5'hydroxymethyl-2'furyl)-1-benzyl indazole (YC-1) (a benzyl indazole derivative) and the inhibition of PDE 5 by T-1032 were less effective in pulmonary vascular rings from CDH animals. The YC-1-induced vasodilation in rings from CDH animals was higher when associated with the PDE 5 inhibitor T-1032.

Conclusions: Guanylate cyclase and PDE 5 play a role in controlling pulmonary vascular tone in fetal lambs with or without CDH. Both enzymes seem to be impaired in fetal lambs with CDH.
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http://dx.doi.org/10.1016/j.jpedsurg.2010.12.015DOI Listing
August 2011

The surgical management of atypical forms of congenital hyperinsulinism.

Semin Pediatr Surg 2011 Feb;20(1):54-5

Department of Pediatric Surgery, AP-HP Hôpital Necker-Enfants Malades, Université Paris Descartes, Paris, France.

Beyond the 2 classical forms of congenital hyperinsulinism, focal and diffuse, we report our experience on the surgical treatment of atypical forms. We define 2 subtypes among these atypical forms of hyperinsulinism: in case of a giant focal form the surgical strategy is the same as in focal forms. In case of hyperinsulinism caused by a mosaic, our experience suggests the benefit of a limited resection from the tail to the body of the pancreas.
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http://dx.doi.org/10.1053/j.sempedsurg.2010.10.003DOI Listing
February 2011

Familial focal congenital hyperinsulinism.

J Clin Endocrinol Metab 2011 Jan 13;96(1):24-8. Epub 2010 Oct 13.

Department of Endocrinology, Great Ormond Street Hospital for Children, National Health Service Trust, University College London, London, United Kingdom.

Background: Congenital hyperinsulinism (CHI) is a cause of persistent hypoglycemia. Histologically, there are two subgroups, diffuse and focal. Focal CHI is a consequence of two independent events, inheritance of a paternal mutation in ABCC8/KCNJ11 and paternal uniparental isodisomy of chromosome 11p15 within the embryonic pancreas, leading to an imbalance in the expression of imprinted genes. The probability of both events occurring within siblings is rare.

Aim: We describe the first familial form of focal CHI in two siblings.

Patients And Methods: The proband presented with medically unresponsive CHI. He underwent pancreatic venous sampling and Fluorine-18-L-dihydroxyphenylalanine positron emission tomography scan, which localized a 5-mm focal lesion in the isthmus of the pancreas. The sibling presented 8 yr later also with medically unresponsive CHI. An Fluorine-18-L-dihydroxyphenylalanine positron emission-computerised tomography scan showed a 7-mm focal lesion in the posterior section of the head of the pancreas. Both siblings were found to be heterozygous for two paternally inherited ABCC8 mutations, A355T and R1494W. Surgical removal of the focal lesions in both siblings cured the Hyperinsulinaemic hypoglycaemia.

Conclusion: This is the first report of focal CHI occurring in siblings. Genetic counseling for families of patients with focal CHI should be recommended, despite the rare risk of recurrence of this disease.
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http://dx.doi.org/10.1210/jc.2010-1524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3217340PMC
January 2011

Congenital hyperinsulinism.

Early Hum Dev 2010 May 13;86(5):287-94. Epub 2010 Jun 13.

Hospital Necker-Enfants Malades, Paris, France.

Congenital hyperinsulinism (CHI or HI) is a condition leading to recurrent hypoglycemia due to an inappropriate insulin secretion by the pancreatic islet beta cells. HI has two main characteristics: a high glucose requirement to correct hypoglycemia and a responsiveness of hypoglycemia to exogenous glucagon. HI is usually isolated but may be rarely part of a genetic syndrome (e.g. Beckwith-Wiedemann syndrome, Sotos syndrome etc.). The severity of HI is evaluated by the glucose administration rate required to maintain normal glycemia and the responsiveness to medical treatment. Neonatal onset HI is usually severe while late onset and syndromic HI are generally responsive to a medical treatment. Glycemia must be maintained within normal ranges to avoid brain damages, initially with glucose administration and glucagon infusion then, once the diagnosis is set, with specific HI treatment. Oral diazoxide is a first line treatment. In case of unresponsiveness to this treatment, somatostatin analogues and calcium antagonists may be added, and further investigations are required for the putative histological diagnosis: pancreatic (18)F-fluoro-L-DOPA PET-CT and molecular analysis. Indeed, focal forms consist of a focal adenomatous hyperplasia of islet cells, and will be cured after a partial pancreatectomy. Diffuse HI involves all the pancreatic beta cells of the whole pancreas. Diffuse HI resistant to medical treatment (octreotide, diazoxide, calcium antagonists and continuous feeding) may require subtotal pancreatectomy which post-operative outcome is unpredictable. The genetics of focal islet-cells hyperplasia associates a paternally inherited mutation of the ABCC8 or the KCNJ11 genes, with a loss of the maternal allele specifically in the hyperplasic islet cells. The genetics of diffuse isolated HI is heterogeneous and may be recessively inherited (ABCC8 and KCNJ11) or dominantly inherited (ABCC8, KCNJ11, GCK, GLUD1, SLC16A1, HNF4A and HADH). Syndromic HI are always diffuse form and the genetics depend on the syndrome. Except for HI due to potassium channel defect (ABCC8 and KCNJ11), most of these HI are sensitive to diazoxide. The main points sum up the management of HI: i) prevention of brain damages by normalizing glycemia and ii) screening for focal HI as they may be definitively cured after a limited pancreatectomy.
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http://dx.doi.org/10.1016/j.earlhumdev.2010.05.003DOI Listing
May 2010

Combining keratinocyte growth factor transfection into the airways and tracheal occlusion in a fetal sheep model of congenital diaphragmatic hernia.

J Gene Med 2010 May;12(5):413-22

EA 3102, Hôpital Robert Debré, AP-HP, Paris, France.

Background: In utero tracheal occlusion (TO) has been developed to improve the lung hypoplasia associated with congenital diaphragmatic hernia (CDH). However, although TO stimulates fetal lung growth, it results in a decrease of alveolar type II cells (ATII) and surfactant production. Because keratinocyte growth factor (KGF) is a potent stimulus of ATII proliferation and maturation, we evaluated, in a fetal lamb model of CDH, a gene therapy strategy combining TO and ovine KGF transfection into the fetal airways using bisguanidinium-tren-cholesterol/dioleoyl-phosphatidylethanolamine (BGTC/DOPE) cationic liposomes.

Methods: Three groups of sheep fetuses with CDH and a group of normal fetuses were studied. The fetuses of the three groups with CDH (KGF, Medium and Hernia groups) underwent surgery at 85 days of gestation to create a diaphragmatic hernia. The KGF and medium group fetuses underwent a second surgery step at day 125 to perform TO associated with injection of the KGF transfection mixture (KGF group) or control medium (Medium group), whereas the fetuses of the Hernia group were left untreated. Normal fetuses were used as a control (Normal group). All fetuses were euthanized at 132 days of gestation and various analytical studies [lung weight, radial alveolar count (RAC), KGF and surfactant protein B (SPB) expression, number of ATII cells] were performed to assess the efficiency of KGF transfection and its effects on fetal lung development.

Results: TO was associated with lung hyperplasia and increased RAC in the Medium and KGF groups versus the Hernia group. Expression of KGF was increased in the KGF group compared to all other groups and was associated with an increased synthesis of SPB by alveolar cells and an ectopic synthesis of SPB by bronchiolar cells compared to TO treatment alone.

Conclusions: Thus, BGTC/DOPE liposomes can mediate efficient KGF transfection into the airways in a fetal sheep model of CDH. Furthermore, combining KGF transfection and TO resulted not only (as did TO alone) in the correction of the CDH-associated lung hypoplasia and decreased RAC, but also in increased SPB synthesis, suggesting a better maturation of the re-growing lung (compared to TO alone). Additional studies are required to further explore the therapeutic potential of such a combined strategy; in particular, studies evaluating the lung function of in utero-treated CDH lamb newborns.
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http://dx.doi.org/10.1002/jgm.1451DOI Listing
May 2010

Value of 18F-fluoro-L-dopa PET in the preoperative localization of focal lesions in congenital hyperinsulinism.

Radiology 2009 Oct 25;253(1):216-22. Epub 2009 Aug 25.

Departments of Pediatric Surgery, Radiology, Pathology, and Pediatrics, Necker-Enfants Malades Hospital, AP-HP, 75015 Paris, France.

Purpose: To retrospectively compare fluorine 18 ((18)F) fluoro-L-dopa positron emission tomography (PET) and pancreatic venous sampling (PVS) in the preoperative differentiation of diffuse from focal congenital hyperinsulinism (CHI) and localization of focal lesions.

Materials And Methods: This study was approved by the institutional ethical committee, and informed consent for the research study was obtained from the parents of all subjects. Fifty-one patients evaluated for focal CHI between January 1, 1995, and January 31, 2008, were included. Thirty five underwent PVS evaluation alone, and 16 underwent a PET evaluation alone. The sensitivity values of each technique for the diagnosis and localization of focal lesions were compared in regard to results of surgery and pathologic analyses. In each patient, perioperative treatment was reviewed, and the presence of postoperative hypoglycemia was assessed as evidence of incomplete resection. Comparisons of the sensitivity values and recurrence rates were performed by using the Fisher exact test in regard to the number of patients. Comparisons of median age, weight, or number of biopsies were performed with a two-tailed unpaired Mann-Whitney U test. A difference with P < .05 was considered significant.

Results: For PVS and PET groups, there was no error in differentiating focal from diffuse forms. PVS was not completed in four of 35 patients. In 27 (87%) of 31 patients in whom PVS was completed and 13 (81%) of 16 patients in whom PET was completed, preoperative localization of the focal lesion was in accordance with the surgical findings (P = .7). Although not significant, the number of biopsies performed before discovering the focal lesion was higher in the PET group compared with the PVS group (P = .06). Inadequate localization occurred in two (6%) patients in the PVS group and five (31%) patients in the PET group at initial preoperative imaging study; these patients underwent repeat surgery for residual CHI (P = .03).

Conclusion: (18)F-fluoro-L-dopa PET is equivalent to PVS in the characterization of CHI but does not provide localization of the lesion as precisely as does PVS.
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http://dx.doi.org/10.1148/radiol.2532081445DOI Listing
October 2009

Female epispadias management: perineal urethrocervicoplasty versus classical Young-Dees procedure.

J Urol 2009 Oct 18;182(4 Suppl):1807-11. Epub 2009 Aug 18.

Department of Pediatric Surgery and Urology, Assistance Publique-Hôpitaux de Paris Hôpital Necker Enfants-Malades, Paris, France.

Purpose: We compared the functional results of 1-stage perineal urethrocervicoplasty and vulvoplasty vs the classic Young-Dees procedure for incontinent female epispadias.

Materials And Methods: We treated 14 female patients with incontinent epispadias between 1997 and 2007, of whom 7 each underwent the Young-Dees procedure until 2004 (group 1) and 1-stage urethrocervicoplasty with vulvoplasty through a perineal subsymphyseal approach (group 2). We retrospectively compared patient age at surgery, bladder capacity, continence outcome and postoperative morbidity.

Results: The groups were comparable except for age at procedure. In group 1 vs 2 surgery was performed at a median age of 6 vs 4 years. In groups 1 and 2 median preoperative bladder capacity was 120 and 100 cc, and mean followup was 8 and 2.5 years, respectively. Six group 1 patients achieved continence, including 5 with overnight continence, but 5 required additional surgery to enhance continence or voiding, including pericervical injections of bulking agents (3), cervicotomy or urethral calibration (4) and enterocystoplasty (1). Two patients required long-term clean intermittent catheterization, 4 underwent upper tract dilation postoperatively and 4 had a total of 8 episodes of febrile urinary tract infection. Six group 2 patients were continent, including 3 with overnight continence (p = 1). None required clean intermittent catheterization even temporarily or any additional surgery (p = 0.02). Only 2 patients had a febrile urinary tract infection (p = 0.25).

Conclusions: Reconstructing the bladder neck and urethra via a perineal approach for female epispadias is promising. Surgery may be performed earlier with similar continence results, less postoperative morbidity and less need for additional surgery. Long-term studies are needed to confirm these preliminary results.
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http://dx.doi.org/10.1016/j.juro.2009.04.087DOI Listing
October 2009