Publications by authors named "Arnaud Picard"

75 Publications

DIVA, a 3D virtual reality platform, improves undergraduate craniofacial trauma education.

J Stomatol Oral Maxillofac Surg 2020 Sep 29. Epub 2020 Sep 29.

Assistance Publique - Hôpitaux de Paris, Service de Chirurgie Maxillo-Faciale et Chirurgie Plastique, Hôpital Universitaire Necker - Enfants Malades, Université Paris Descartes, Université de Paris, Paris, France.

Craniofacial fractures management is challenging to teach due to the complex anatomy of the head, even when using three-dimensional CT-scan images. DIVA is a software allowing the straightforward visualization of CT-scans in a user-friendly three-dimensional virtual reality environment. Here, we assess DIVA as an educational tool for craniofacial trauma for undergraduate medical students. Three craniofacial trauma cases (jaw fracture, naso-orbital-ethmoid complex fracture and Le Fort 3 fracture) were submitted to 50 undergraduate medical students, who had to provide diagnoses and treatment plans. Each student then filled an 8-item questionnaire assessing satisfaction, potential benefit, ease of use and tolerance. Additionally, 4 postgraduate students were requested to explore these cases and to place 6 anatomical landmarks on both virtual reality renderings and usual slice-based three-dimensional CT-scan visualizations. High degrees of satisfaction (98%) without specific tolerance issues (86%) were reported. The potential benefit in a better understanding of craniofacial trauma using virtual reality was reported by almost all students (98%). Virtual reality allowed a reliable localization of key anatomical landmarks when compared with standard three-dimensional CT-scan visualization. Virtual reality interfaces such DIVA are beneficial to medical students for a better understanding of craniofacial trauma and allow a reliable rendering of craniofacial anatomy.
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http://dx.doi.org/10.1016/j.jormas.2020.09.009DOI Listing
September 2020

Surgery-first orthognathic approach vs conventional orthognathic approach: A systematic review of systematic reviews.

J Stomatol Oral Maxillofac Surg 2021 Apr 5;122(2):162-172. Epub 2020 Sep 5.

School of Dentistry, Department of Health Sciences, Magna Graecia University of Catanzaro, Catanzaro, Italy; Department of Oral and Maxillofacial Surgery, Magna Graecia University, Catanzaro, Italy. Electronic address:

Surgery-first approach (SFA) has been introduced as an alternative for conventional orthognathic approach (COA) in the treatment of patients with dentoskeletal deformities. This review aimed to evaluate skeletal stability, treatment time, surgical complications, and quality of life in SFA and COA. Six databases were accessed up to May 2020 to obtain all systematic reviews (SRs). After title and abstract reading, data extraction was performed from eligible SRs. The methodological quality was calculated for the included SRs using the last version of A Measurement Tool to Assess Systematic Review (AMSTAR-2). Ten SRs were included in this review. A good stability of the jaws was assessed both with SFA and COA by most of low- or critically low-quality SRs. Less treatment time was reported for SFA than COA with a moderate quality level. Slightly higher complications rate was recorded with SFA than COA by SRs with low or moderate quality. A better quality of life with SFA than COA was reported by moderate- or low-quality SRs. SFA may represent a reasonable alternative to COA. However, for the heterogeneity of the included SRs, well-designed studies with a long term follow-up are needed to clarify the findings of this analysis.
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http://dx.doi.org/10.1016/j.jormas.2020.08.008DOI Listing
April 2021

Cherubism as a systemic skeletal disease: evidence from an aggressive case.

BMC Musculoskelet Disord 2020 Aug 21;21(1):564. Epub 2020 Aug 21.

Laboratoire de Physiopathologie Orale Moléculaire, INSERM UMRS 1138, Equipe 5, Centre de Recherche de Cordeliers, 75006, Paris, France.

Background: Cherubism is a rare autosomal dominant genetic condition caused by mutations in the SH3BP2 gene. This disease is characterized by osteolysis of the jaws, with the bone replaced by soft tissue rich in fibroblasts and multinuclear giant cells. SH3BP2 is a ubiquitous adaptor protein yet the consequences of SH3BP2 mutation have so far been described as impacting only face. Cherubism mouse models have been generated and unlike human patients, the knock-in mice exhibit systemic bone loss together with a systemic inflammation.

Case Presentation: In light of these observations, we decided to search for a systemic cherubism phenotype in a 6-year-old girl with an aggressive cherubism. We report here the first case of cherubism with systemic manifestations. Bone densitometry showed low overall bone density (total body Z-score = - 4.6 SD). Several markers of bone remodelling (CTx, BALP, P1NP) as well as inflammation (TNFα and IL-1) were elevated. A causative second-site mutation in other genes known to influence bone density was ruled out by sequencing a panel of such genes.

Conclusions: If this systemic skeletal cherubism phenotype should be confirmed, it would simplify the treatment of severe cherubism patients and allay reservations about applying a systemic treatment such as those recently published (tacrolimus or imatinib) to a disease heretofore believed to be localised to the jaws.
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http://dx.doi.org/10.1186/s12891-020-03580-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441549PMC
August 2020

Sleep-disordered breathing in children with pycnodysostosis.

Am J Med Genet A 2020 01 3;182(1):122-129. Epub 2019 Nov 3.

ASV Santé, Gennevilliers, France.

Upper airway obstruction is a common feature in pycnodysostosis and may cause obstructive sleep apnea (OSA). The aim of our study was to analyze sleep-disordered breathing and respiratory management in children with pycnodysostosis. A retrospective review of the clinical charts and sleep studies of 10 consecutive children (three girls and seven boys) with pycnodysostosis seen over a time period of 10 years was performed. Six patients had severe OSA and/or nocturnal hypoventilation and were started on continuous positive airway pressure (CPAP) as a first treatment at a median age of 3.4 ± 2.6 years, because of the lack of indication of any surgical treatment. Three patients could be weaned after several years from CPAP after spontaneous improvement (two patients) or multiple upper airway surgeries (one patient). Three patients had upper airway surgery prior to their first sleep study with two patients still needing CPAP during their follow-up. Only one patient never developed OSA. Patients with pycnodysostosis are at a high risk of severe OSA, underlying the importance of a systematic screening for sleep-disordered breathing. Multidisciplinary care is mandatory because of the multilevel airway obstruction. CPAP is very effective and well accepted for treating OSA.
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http://dx.doi.org/10.1002/ajmg.a.61393DOI Listing
January 2020

Conservative management is effective in unicystic ameloblastoma occurring from the neonatal period: A case report and a literature review.

Oral Surg Oral Med Oral Pathol Oral Radiol 2020 May 6;129(5):e234-e242. Epub 2019 Sep 6.

Department of Maxillofacial and Plastic Surgery, Rare Diseases Reference Center Coordinator for Clefts and Facial Malformations, Hôpital Universitaire Necker-Enfants Malades, Paris, France; Université Paris Descartes-Sorbonne Paris Cité, Paris, France.

Unicystic ameloblastoma (UA), a benign odontogenic tumor of the jaw, represents less than a third of all ameloblastomas and seems less aggressive than other types of ameloblastoma. We present here the first case of UA that developed prenatally and was successfully managed in the early neonatal period with marsupialization and curettage performed carefully to avoid injury to the tooth germ. BRAF and SMO mutations were not detected. After 2 years of follow-up, complete reossification and normal eruption of deciduous teeth were noted, and there was no recurrence of UA. We recommend conservative treatment of UA in the pediatric population to avoid loss of and/or injury to the tooth germ, provided close follow-up is carried out all through the individual's growth for early detection of potential recurrences, growth impairments, or tooth eruption disorders. The intratumoral somatic mutational status of BRAF, SMO, RAS family, and FGFR2 may help determine personalized targeted treatment, particularly in case of recurrence.
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http://dx.doi.org/10.1016/j.oooo.2019.08.009DOI Listing
May 2020

Modeling of the human mandibular periosteum material properties and comparison with the calvarial periosteum.

Biomech Model Mechanobiol 2020 Apr 11;19(2):461-470. Epub 2019 Sep 11.

UME, ENSTA Paris, Palaiseau, France.

Knowledge of mandibular periosteum mechanical properties is fundamental for understanding its role in craniofacial growth, in trauma and bone regeneration. There is a lack in the literature regarding mechanical behavior of the human periosteum, including both experimental and modeling aspects. The proposed study involves tensile tests of periosteum samples from different locations including two locations of human mandibular periosteum: lingual and vestibular, compared with samples from various locations of the calvarial periosteum. We propose to analyze the tensile response of the mandibular periosteum using a model, initially applied on the skin, and based on a structural approach involving the mechanical properties of the corrugation of the collagen. Two different approaches for the model parameters' identification are proposed: (1) identification from experimental curve fitting and (2) identification from histological study. This approach allows us to compare parameters extracted from the traction test fitting to structural parameters measured on periosteum histological slices. Concerning experimental aspects, we showed significant differences, in terms of stiffness, between calvarial and mandibular periostea. (The mean final stiffness is [Formula: see text] for the mandible versus [Formula: see text] for the calvaria.) About modeling, we succeed to capture the correct mechanical behavior for the periosteum, and the statistical analysis showed that certain parameters from the geometric data and traction data are significantly comparable (e.g., [Formula: see text] for [Formula: see text]). However, we also observed a discrepancy between these two approaches for the elongation at which the fibril has become straight ([Formula: see text]).
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http://dx.doi.org/10.1007/s10237-019-01221-6DOI Listing
April 2020

Oral health related quality of life of children and adolescents affected by rare orofacial diseases: a questionnaire-based cohort study.

Orphanet J Rare Dis 2019 06 4;14(1):124. Epub 2019 Jun 4.

Centre de Reference, Maladies Orales et Dentaires Rares, Hopital Rothschild, APHP, Paris, France.

Background: Rare diseases affecting the teeth, the oral cavity and the face are numerous, each of them present specific characteristics, and is a life-long condition. The aim of the study was to assess the association between Oral health-related quality of life (OHRQoL), and demographic characteristics, clinical and dental factors, and psycho-social characteristics to investigate that oral symptoms are not the main factors underlying a decrease in OHRQoL.

Material And Methods: We conducted a national cohort study in French centres for rare diseases (RD) specialized in orofacial diseases. The inclusion criteria were: to have received care in RD centres over the last 5 years (2012-2017) and to have been between 6 and 17 years of age on September 1, 2017. Patients were invited to answer a questionnaire composed of socio-demographic, clinical and dental questions, psychosocial questions and then fill in the Child-OIDP Index. At the end of the questionnaire, a free space was left for the patient to add a verbatim comment to provide qualitative data. Thematic analysis was used to analyze the verbatim answers.

Results: Complete data were available for 110 patients. The sample included 44.5% boys and 55.5% girls. Ages ranged from 6 to 17 years old and 68.2% were between 6 to 12 years old and 31.8% were between 13 and 17 years old. Factor associated with a lower OHRQoL were: being a girl (p = 0.03), renouncement to dental care for financial reasons (p = 0.01), having syndromic disease (p = 0.01), having a problem with tooth shape and color (p = 0.03), feeling isolated, alone and different from other children (p = 0.003 and p = 0.02). Qualitative analysis highlighted very little recourse to psychological care and patients reported great anxiety and fear about the future.

Conclusion: OHRQoL of children suffering from these diseases is impaired, especially from the psychosocial point of view but also from that of the course of treatment and access to care. There is a need to improve the legibility of care pathways and the financial coverage of treatments.
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http://dx.doi.org/10.1186/s13023-019-1109-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549379PMC
June 2019

Pediatric Nasal Reconstruction by Washio Procedure.

Facial Plast Surg 2019 Jun 17;35(3):286-293. Epub 2019 May 17.

Department of Maxillofacial and Plastic Surgery, Rare Diseases Reference Center Coordinator for Clefts and Facial Malformations, Hôpital Universitaire Necker-Enfants Malades, Paris, France.

The use of the Washio retroauricular flap for nasal reconstruction has been infrequently covered in recent literature, particularly concerning the pediatric population. A retrospective study was conducted between 2014 and 2018 and included all pediatric patients who underwent a Washio retroauricular flap procedure for nasal reconstruction operated on by the same surgeon at a referral center for pediatric plastic and maxillofacial surgery. The mean age at the time of the first stage of the Washio procedure was just under 8 years of age (range: 6 years 3 months-8 years 10 months). The Washio retroauricular flap procedure was successfully employed in three patients with three different anatomical defects, including the nasal alae, nasal tip, and columella, without postoperative healing complications. Arguably, the Washio method is sufficiently versatile to be used in various defect types, allows space and planning for subsequent surgical corrections, avoids additional visible scarring of the face, and spares flaps that may be required at the end of the growth, such as the pedicled forehead flap. It is a safe procedure, provided that at least a two-stage procedure is performed, and a progressive postoperative verticalization is prescribed to limit venous drainage complications.
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http://dx.doi.org/10.1055/s-0039-1688703DOI Listing
June 2019

Local Inhibition of MEK/Akt Prevents Cellular Growth in Human Congenital Melanocytic Nevi.

J Invest Dermatol 2019 09 3;139(9):2004-2015.e13. Epub 2019 May 3.

Saint-Antoine Research Center, INSERM UMRS_938, Paris, France; Université Paris-Descartes, Paris, France; AP-HP, Hôpital Cochin, Department of Dermatology, Paris, France. Electronic address:

The management of large congenital melanocytic nevi (lCMN) is based exclusively on iterative surgical procedures in the absence of validated medical therapy. The aim of our study was to develop an intra-lesional medical treatment for lCMN. Seventeen patients harboring NRAS-mutated lCMN were included. Nevocytes obtained from lCMN displayed an overactivation of mitogen-activated protein kinase and phosphoinositide 3-kinase (Akt) pathways. Mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK) and Akt inhibitors reduced the nevosphere diameter in sphere-forming assays, as well as cell viability and proliferation in in vitro assays. Standardized lCMN explants were then cultured ex vivo with the same inhibitors, which induced a decrease in MelanA+ and Sox10+ cells in both epidermis and dermis. Finally, intradermal injections of these inhibitors were administered within standardized lCMN xenografts in Rag2 mice. They induced a dramatic decrease in nevocytes in treated xenografts, which persisted 30 days after the end of treatment. Using original nevus explant and xenograft preclinical models, we demonstrated that intradermal MEK/Akt inhibition might serve as neoadjuvant therapy for the treatment of NRAS-mutated congenital melanocytic nevi to avoid iterative surgeries.
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http://dx.doi.org/10.1016/j.jid.2019.03.1156DOI Listing
September 2019

Craniofacial bone atrophy in Parry Romberg syndrome demonstrated using a Bayesian hierarchical model.

J Craniomaxillofac Surg 2019 Jun 8;47(6):909-914. Epub 2019 Apr 8.

Assistance Publique - Hôpitaux de Paris, Hôpital Necker - Enfants Malades, Service de chirurgie maxillo-faciale et plastique, Université Sorbonne Paris Cité, Université Paris Descartes, Paris, France.

Purpose: Parry Romberg syndrome (PRS) is a condition characterized by progressive hemifacial atrophy, predominantly affecting the soft tissues. Associated bone retraction is a common clinical feature of PRS but has never been assessed. Here we used 3D imaging and Bayesian statistics in order to demonstrate and quantify bone atrophy in PRS.

Materials And Methods: Ten non-operated patients with PRS (4/10 males) and 12 age-matched controls (7/12 males) were included into the study. The average age at CT-scan was 9.67 ± 4.13 years for PRS patients and 12.5 ± 4.37 years for controls. Soft and hard tissue atrophy levels were quantified using computed tomography scans, based on the distances between surfaces of the affected side and the non-affected contralateral side, both for the skin and the bone. We used a hierarchical Bayesian model with clinical priors in order to assess the relationship between hard and soft tissue atrophies.

Results: PRS patients had significant hard tissue atrophy, and atrophy extents were similar for soft and hard tissues. There was a trend for a correlation between the extent of hard tissue retraction and the extent of soft tissue retraction, and we could not demonstrate that the relationship between hard and soft tissue retractions was different in PRS and controls.

Conclusion: Our results indicated that bone atrophy was most probably a primary process rather than a phenomenon secondary to soft tissue retraction. We have provided the first assessment of bone atrophy in PRS patients using Bayesian statistics.
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http://dx.doi.org/10.1016/j.jcms.2019.03.032DOI Listing
June 2019

Missense Variants in the Histone Acetyltransferase Complex Component Gene TRRAP Cause Autism and Syndromic Intellectual Disability.

Authors:
Benjamin Cogné Sophie Ehresmann Eliane Beauregard-Lacroix Justine Rousseau Thomas Besnard Thomas Garcia Slavé Petrovski Shiri Avni Kirsty McWalter Patrick R Blackburn Stephan J Sanders Kévin Uguen Jacqueline Harris Julie S Cohen Moira Blyth Anna Lehman Jonathan Berg Mindy H Li Usha Kini Shelagh Joss Charlotte von der Lippe Christopher T Gordon Jennifer B Humberson Laurie Robak Daryl A Scott Vernon R Sutton Cara M Skraban Jennifer J Johnston Annapurna Poduri Magnus Nordenskjöld Vandana Shashi Erica H Gerkes Ernie M H F Bongers Christian Gilissen Yuri A Zarate Malin Kvarnung Kevin P Lally Peggy A Kulch Brina Daniels Andres Hernandez-Garcia Nicholas Stong Julie McGaughran Kyle Retterer Kristian Tveten Jennifer Sullivan Madeleine R Geisheker Asbjorg Stray-Pedersen Jennifer M Tarpinian Eric W Klee Julie C Sapp Jacob Zyskind Øystein L Holla Emma Bedoukian Francesca Filippini Anne Guimier Arnaud Picard Øyvind L Busk Jaya Punetha Rolph Pfundt Anna Lindstrand Ann Nordgren Fayth Kalb Megha Desai Ashley Harmon Ebanks Shalini N Jhangiani Tammie Dewan Zeynep H Coban Akdemir Aida Telegrafi Elaine H Zackai Amber Begtrup Xiaofei Song Annick Toutain Ingrid M Wentzensen Sylvie Odent Dominique Bonneau Xénia Latypova Wallid Deb Sylvia Redon Frédéric Bilan Marine Legendre Caitlin Troyer Kerri Whitlock Oana Caluseriu Marine I Murphree Pavel N Pichurin Katherine Agre Ralitza Gavrilova Tuula Rinne Meredith Park Catherine Shain Erin L Heinzen Rui Xiao Jeanne Amiel Stanislas Lyonnet Bertrand Isidor Leslie G Biesecker Dan Lowenstein Jennifer E Posey Anne-Sophie Denommé-Pichon Claude Férec Xiang-Jiao Yang Jill A Rosenfeld Brigitte Gilbert-Dussardier Séverine Audebert-Bellanger Richard Redon Holly A F Stessman Christoffer Nellaker Yaping Yang James R Lupski David B Goldstein Evan E Eichler Francois Bolduc Stéphane Bézieau Sébastien Küry Philippe M Campeau

Am J Hum Genet 2019 03 28;104(3):530-541. Epub 2019 Feb 28.

Centre Hospitalier Universitaire Sainte-Justine Research Centre, University of Montreal, Montreal, QC H3T 1C5, Canada; Department of Pediatrics, University of Montreal, Montreal, QC H3T1J4, Canada. Electronic address:

Acetylation of the lysine residues in histones and other DNA-binding proteins plays a major role in regulation of eukaryotic gene expression. This process is controlled by histone acetyltransferases (HATs/KATs) found in multiprotein complexes that are recruited to chromatin by the scaffolding subunit transformation/transcription domain-associated protein (TRRAP). TRRAP is evolutionarily conserved and is among the top five genes intolerant to missense variation. Through an international collaboration, 17 distinct de novo or apparently de novo variants were identified in TRRAP in 24 individuals. A strong genotype-phenotype correlation was observed with two distinct clinical spectra. The first is a complex, multi-systemic syndrome associated with various malformations of the brain, heart, kidneys, and genitourinary system and characterized by a wide range of intellectual functioning; a number of affected individuals have intellectual disability (ID) and markedly impaired basic life functions. Individuals with this phenotype had missense variants clustering around the c.3127G>A p.(Ala1043Thr) variant identified in five individuals. The second spectrum manifested with autism spectrum disorder (ASD) and/or ID and epilepsy. Facial dysmorphism was seen in both groups and included upslanted palpebral fissures, epicanthus, telecanthus, a wide nasal bridge and ridge, a broad and smooth philtrum, and a thin upper lip. RNA sequencing analysis of skin fibroblasts derived from affected individuals skin fibroblasts showed significant changes in the expression of several genes implicated in neuronal function and ion transport. Thus, we describe here the clinical spectrum associated with TRRAP pathogenic missense variants, and we suggest a genotype-phenotype correlation useful for clinical evaluation of the pathogenicity of the variants.
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http://dx.doi.org/10.1016/j.ajhg.2019.01.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6407527PMC
March 2019

Mandibular symphyseal distraction osteogenesis: 20 years of experience treating transverse deficiencies with an internal hybrid device.

J Craniomaxillofac Surg 2019 Apr 11;47(4):586-591. Epub 2019 Jan 11.

Department of Maxillofacial and Plastic Surgery, National Reference Center for Cleft Lip and Palate, Hôpital Universitaire Necker-Enfants Malades, Paris, France; Université Paris Descartes-Sorbonne Paris Cité, Paris, France. Electronic address:

Introduction: Transverse mandibular deficiency has been traditionally managed by orthodontic compensation. However, without resolving the underlying skeletal hypoplasia it leads to high relapse rates. Few studies have reviewed the long-term experience and potential complications of mandibular symphyseal distraction osteogenesis (MSDO) as an alternative treatment method.

Materials And Method: A retrospective review of 20 patients (range: 4-19 years; mean: 11.9 years) treated with a hybrid MSDO device over the period of 1996-2017 was conducted. Epidemiological data, medical and dental history as well as photographic and cephalometric analyses were carried out. Furthermore, pre-operative and long-term post-operative status including dental occlusion and tooth-jaw discrepancies were recorded.

Results: The distraction amount ranged from 3 mm to 15 mm (mean: 10 mm) with an average distraction period of 30.9 days. In long-term follow-up (mean: 7.3 years), 14 patients presented a class I and 6 patients presented a class II relationship. Correction of overjet, tooth jaw discrepancy and arch length discrepancy were obtained in 18, 20 and 17 cases respectively. A device malfunction was experienced in 6 patients.

Conclusion: Mandibular widening using a hybrid MSDO device can be efficiently and safely performed in a paediatric population. Further studies confirming our results and analysing facial aesthetic outcomes are warranted.
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http://dx.doi.org/10.1016/j.jcms.2019.01.001DOI Listing
April 2019

Severity of Retrognathia and Glossoptosis Does Not Predict Respiratory and Feeding Disorders in Pierre Robin Sequence.

Front Pediatr 2018 20;6:351. Epub 2018 Nov 20.

Department of Pediatrics, APHP, Hôpital Universitaire Necker-Enfants Malades, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.

Pierre Robin sequence (PRS) may lead to life-threatening respiratory and feeding disorders. With the aim to analyse the association of the severities of retrognathia and glossoptosis with those of respiratory and feeding disorders, we retrospectively studied a series of 50 infants with retrognathia, glossoptosis, cleft palate, and airway obstruction. The patients were managed from birth to at least 6 years of age by a single pediatric team at the Armand Trousseau Hospital in Paris within a 12 years period (2000-2012). Retrognathia and glossoptosis were graded in the neonatal period according to a specific clinical examination. Ventilation assistance was required for 32/50 (64%) patients, and enteral feeding for 41/50 (82%). The grades of retrognathia and glossoptosis and the severity of respiratory disorders did not differ between patients with isolated PRS and syndromic PRS. Severe respiratory disorders were more common and long-lasting feeding (>12 months) was more frequently required in patients with syndromic PRS compared with isolated PRS (42 vs. 13%, = 0.04 and 42 vs. 4%, < 0.01 respectively). Using univariate analysis, neurological impairments and laryngomalacia were associated with severe respiratory disorders [Odds ratio (OR) 5.0, 95% CI 1.3-19.6; and OR 14.6, 95% CI 1.3-161.4; < 0.05] as well as with long-lasting feeding (>12 months) disorders (OR 18.6, 95% CI 3.9-89.2 and OR 20.4, 95% CI 3,4-122.8; < 10). Syndromic SPR status was also associated with severe respiratory disorders (OR 4.9, 95% CI 1-32.5; < 0.05). Using multivariate analysis, only syndromic PRS status was predictive for severe respiratory disorders (adjusted OR 8, 95% CI 1.47-44.57; < 0.05); and only neurological impairments remained a significant risk for long lasting feeding disorders (>12 months) (adjusted OR 21.72, 95% CI 3.4-138.63; < 10). The grades of retrognathia and glossoptosis were not predictive factors for the severity of respiratory and feeding disorders. : In children with PRS, the severity of clinical conditions may not correlate with anatomic variables but rather with laryngeal abnormalities, neurological impairement and syndromic PRS status.
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http://dx.doi.org/10.3389/fped.2018.00351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6256711PMC
November 2018

Ewing's Sarcoma of the Head and Neck: Margins are not just for surgeons.

Cancer Med 2018 12 17;7(12):5879-5888. Epub 2018 Nov 17.

Department of Oncology for Child and Adolescents, Gustave Roussy, Villejuif, France.

Background, Methods: To describe the characteristics, treatments (systemic/local), and outcome (oncological/functional) of French patients with head and neck Ewing's sarcomas (HNES) registered in the Euro-Ewing 99 (EE99) database. Specific patient-level data were reviewed retrospective.

Results: Forty-seven HNES patients in the EE99 database had a median age of 11 years, 89% had bone tumors (skull 55%, mandible 21%, maxilla 11%), 89% had small tumors (<200 mL), and they were rarely metastatic (9%). Local treatment was surgery radiotherapy (55%), exclusively surgery (28%), or radiotherapy (17%). Metastatic relapses occurred in five patients with high relapse risk factors (metastasis at diagnosis, poor histological response, large tumors). Local progression/relapses (LR) after exclusive radiotherapy occurred in three patients with persistent extra-osseous residue and in four patients considered R0 margins (postchemotherapy surgery, without postoperative radiotherapy [PORT]), reclassified by pathological review as R1a. Pathological review reclassified 72% of R0 margins: 11/18 to R1a and 2/18 to R2. Five patients had confirmed R0 margins after postchemotherapy surgery without PORT and had no LR Eight patients had R2 margins (initial surgery without previous chemotherapy, with PORT) and had no LR With a median follow-up of 9.3 years, the 3-year LR rate, EFS, and OS were 84.8%, 78.6%, and 89.3%, respectively. Among the 5-year survivors, 88% had long-term sequelae.

Conclusion: To optimize HNES management, patients should be treated from diagnosis in expert centers with multidisciplinary committees to discuss treatment strategy (type of surgery, need for PORT) and validate surgical margins.
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http://dx.doi.org/10.1002/cam4.1801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6308064PMC
December 2018

Molecular and cellular characterizations of human cherubism: disease aggressiveness depends on osteoclast differentiation.

Orphanet J Rare Dis 2018 09 20;13(1):166. Epub 2018 Sep 20.

INSERM, UMRS 1138 Equipe 5, Laboratoire de Physiopathologie Orale Moléculaire, Centre de Recherche de Cordeliers, 75006, Paris, France.

Background: Cherubism is a rare autosomal dominant disorder of the jaws caused by mutation of the SH3BP2 gene. The bone is replaced by a fibrous granuloma containing multinucleated giant cells. Cells of the cherubism granuloma have never been systematically analyzed. Hence, the aim of this study was to characterize the cells in human cherubism granulomas, to determine the osteoclastic characteristics of the multinucleated giant cells and to investigate the potential role of TNF-α in human cherubism.

Results: Seven granulomas were analyzed in pathology, molecular biology and immunohistochemistry. Granulomas were composed mainly of macrophages or osteoclasts within a fibroblastic tissue, with few lymphoid cells. Myeloid differentiation and nuclear NFATc1 localization were both associated with disease aggressiveness. OPG and RANKL immunohistochemical expression was unexpected in our specimens. Five granuloma cells were cultured in standard and osteoclastogenic media. In culture, cherubism cells were able to differentiate into active osteoclasts, in both osteoclastogenic and standard media. IL-6 was the major cytokine present in the culture supernatants.

Conclusion: Multinucleated giant cells from cherubism granulomas are CD68 positive cells, which differentiate into macrophages in non-aggressive cherubism and into osteoclasts in aggressive cherubism, stimulated by the NFATc1 pathway. This latter differentiation appears to involve a disturbed RANK-L/RANK/OPG pathway and be less TNF-α dependent than the cherubism mouse model.
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http://dx.doi.org/10.1186/s13023-018-0907-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6148781PMC
September 2018

Congenital fibroblastic connective tissue nevi: Unusual and misleading presentations in three infantile cases.

Pediatr Dermatol 2018 Sep 19;35(5):644-650. Epub 2018 Jul 19.

Services de Chirurgie Maxillo-Faciale et Plastique, Assistance Publique-Hôpitaux de Paris, Hôpital Universitaire Necker Enfants-Malades, Université Sorbonne Paris Cité, Université Paris Descartes, Paris, France.

Background: Fibroblastic connective tissue nevi (FCTN) are benign skin conditions characterized by bland spindle cells infiltrating the reticular dermis and the upper subcutis with preservation of adnexal structures. A subset of FCTN expresses CD34, which may cause difficulties in the differential diagnosis, in particular with dermatofibrosarcoma (DFSP). We aim to study clinical and histological main features of congenital FCTN to better understand their heterogeneity.

Methods: We present 3 cases of congenital FCTN with misleading pseudo-tumoral presentations and compare them with published cases in literature. We provide a diagnostic algorithm for congenital neonatal connective tissue tumors.

Results: Clinically, FCTN mostly present as well-limited and nontender plaques or nodules mainly located in the neck and face areas or in the trunk. Histologically, FCTN are composed of irregularly distributed fascicles of bland spindled cells and are defined by a list of fundamental features: (i) no atypia, pleomorphism, or mitotic activity; (ii) skin appendages entrapped but unaffected; (iii) no evidence for malignancy. In most cases CD34 is positive, but in some cases, cells can express SMA or are even CD34- and SMA-.

Conclusion: The initial presentation and natural history of FCTN fit better with a neoplasm than with a hamartoma. Thus, we suggest replacing the term "nevus" with tumor and considering fibroblastic connective tissue tumor (FCTT) as the right denomination of this clinico-pathological entity. FCTTs are difficult to diagnose due to their clinical heterogeneity. Clinical and histological malignant and benign differential diagnoses are discussed.
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http://dx.doi.org/10.1111/pde.13571DOI Listing
September 2018

Contribution of the periosteum to mandibular distraction.

PLoS One 2018 28;13(6):e0199116. Epub 2018 Jun 28.

IMSIA, ENSTA Paris-Tech, Department of Mechanical Engineering, Palaiseau, France.

Mandibular distraction is a surgical process that progressively lengthens bone. To improve the distraction procedure and devices, the load of distraction and the mechanical strain of soft tissues during the process must be determined. We tested the assumption that it could be the periosteum primarily opposing distraction. Therefore we assessed the mechanical properties of the human mandibular periosteum and compared the stress-strain data with the torque measured on the activator during a cadaveric mandibular distraction. A 20 mm horizontal mandibular distraction was performed in 7 cadavers using standard distractors. Torque was measured with a torquemeter placed on the activation rods of the devices, providing a load (Lt) for each millimeter of distraction. In parallel, 18 periosteum samples were harvested from 9 cadaver mandibles. Uniaxial tensile tests were performed on the specimens and an estimated load (Lc) was calculated using periosteal stress-strain data and mandibular dimensions. During the distraction process, we observed an increase of the load Lt from 11.6 to 50.6 N. The periosteum exhibited a nonlinear viscoelastic stress-strain relationship, typical of biological tissues composed of collagen and elastin. The median Lc and Lt were not significantly different for the first millimeter of distraction. We demonstrated the periosteum is primarily responsible for opposing the distraction load.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0199116PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6023199PMC
December 2018

Targeted therapy in patients with PIK3CA-related overgrowth syndrome.

Nature 2018 06 13;558(7711):540-546. Epub 2018 Jun 13.

INSERM U1151, Institut Necker Enfants Malades, Paris, France.

CLOVES syndrome (congenital lipomatous overgrowth, vascular malformations, epidermal naevi, scoliosis/skeletal and spinal syndrome) is a genetic disorder that results from somatic, mosaic gain-of-function mutations of the PIK3CA gene, and belongs to the spectrum of PIK3CA-related overgrowth syndromes (PROS). This rare condition has no specific treatment and a poor survival rate. Here, we describe a postnatal mouse model of PROS/CLOVES that partially recapitulates the human disease, and demonstrate the efficacy of BYL719, an inhibitor of PIK3CA, in preventing and improving organ dysfunction. On the basis of these results, we used BYL719 to treat nineteen patients with PROS. The drug improved the disease symptoms in all patients. Previously intractable vascular tumours became smaller, congestive heart failure was improved, hemihypertrophy was reduced, and scoliosis was attenuated. The treatment was not associated with any substantial side effects. In conclusion, this study provides the first direct evidence supporting PIK3CA inhibition as a promising therapeutic strategy in patients with PROS.
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http://dx.doi.org/10.1038/s41586-018-0217-9DOI Listing
June 2018

Rhabdomyosarcoma and rhabdomyoma associated with nevoid basal cell carcinoma syndrome: Local treatment strategy.

Pediatr Dermatol 2018 Jul 25;35(4):e245-e247. Epub 2018 May 25.

Departments of Maxillofacial and Plastic Surgery, Necker Children Hospital, Assistance Publique-Hôpitaux de Paris, University Paris 5, Paris, France.

This article presents the case of a child presenting with a rhabdomyosarcoma associated with a fetal rhabdomyoma in the setting of nevoid basal cell carcinoma syndrome. Oncologic strategy is discussed.
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http://dx.doi.org/10.1111/pde.13536DOI Listing
July 2018

Predictors of speech outcomes in children with Pierre Robin sequence.

J Craniomaxillofac Surg 2018 Mar 13;46(3):479-484. Epub 2017 Dec 13.

Department of Maxillo-facial and Plastic Surgery, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, Université Paris-Descartes, Paris, France; Centre de Références des Malformations de la Face et de la Cavité Buccale, Paris, France.

Backgound: Pierre Robin sequence (PRS) has worse speech outcomes than isolated cleft palate. We aimed to search for possible associations of phonological outcomes with PRS status (isolated vs syndromic), clinical severity, soft palate muscles deficiency, or surgical procedure.

Methods: We designed a retrospective study of 130 children (male/female ratio: 0.4) with isolated (96) or syndromic (34) PRS with cleft palate. Grading systems were used to classify retrognathia, glossoptosis, and respiratory and feeding disorders. Electromyography was used to investigate levator veli palatini muscles. Hard cleft palate was measured using maxillary casts. Intravelar veloplasty was performed using the Sommerlad's technique. Phonological outcomes were assessed using the Borel-Maisonny classification.

Results: Cleft palate was repaired in one stage (65.5%) or hard palate closure was postponed (34.5%). Velopharyngeal insufficiency was more frequent in syndromic PRS (53%) vs. isolated PRS (30.5%) (p = 0.01), but was not statistically associated with clinical grade, hard cleft palate width, soft palate electromyography, and surgical procedure.

Conclusions: In children with PRS, anatomic variables, initial clinical severity, and soft palate muscle deficiency are not predictors of speech prognosis.
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http://dx.doi.org/10.1016/j.jcms.2017.12.004DOI Listing
March 2018

Melanotic neuroectodermal tumor of infancy (MNTI) of the head and neck: A French multicenter study.

J Craniomaxillofac Surg 2018 Feb 12;46(2):201-206. Epub 2017 Dec 12.

Department of Maxillofacial and Plastic Surgery, Hôpital Universitaire Necker-Enfants Malades, 75015, Paris, France; Université Paris Descartes, 75006, Paris, France; Laboratory for Oral and Molecular Pathology, INSERM, UMRS 1138, Centre de Recherche des Cordeliers, 75006, Paris, France. Electronic address:

Objectives: Melanotic neuroectodermal tumor of infancy (MNTI) of the head and neck is a rare entity with uncertain clinical behavior. Radical surgical resection is the current recommended treatment, however this can cause severe aesthetic and functional sequelae. The aim of this study was to clinically characterize MNTIs and to stratify risk factors that may influence locoregional recurrence.

Methods: A retrospective multicenter study, including 11 patients from eight centers with a confirmed diagnosis of MNTI, was conducted. Epidemiological, clinical, radiological, pathological, and immunohistochemical examinations were reviewed. A statistical analysis using a t-test was conducted to calculate parameters correlating with tumor recurrence.

Results: MNTIs mainly occurred in the maxilla, with a mean age at diagnosis of 3.18 months (range: 0-6 months). Primary surgery was performed on 10 patients, with a clear margin resection on two patients. Overall recurrence rate was 27% with a survival of 100% at time of follow-up. No statistical correlation between recurrence rate, age at diagnosis, localization, resection margins, and pathological and immunohistochemical characteristics could be established.

Conclusion: In our study, locoregional tumor recurrence did not seem to correlate with resection margins, so a conservative surgical approach may need to be considered to avoid functional and aesthetic sequelae.
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http://dx.doi.org/10.1016/j.jcms.2017.12.001DOI Listing
February 2018

Orbital volume and shape in Treacher Collins syndrome.

J Craniomaxillofac Surg 2018 Feb 8;46(2):305-311. Epub 2017 Dec 8.

Assistance Publique - Hôpitaux de Paris, Service de Chirurgie Maxillofaciale et Plastique, Hôpital Universitaire Necker - Enfants Malades, Université Paris-Descartes, Paris, France. Electronic address:

Orbito-palpebral reconstruction is a challenge in Treacher Collins syndrome (TCS). This study investigates orbital phenotypes in TCS using cephalometry and orbital shape analysis. Eighteen TCS and 52 control patients were included in this study, using the Dr Warehouse database. Orbital cephalometry was based on 20 landmarks, 10 planes, 16 angles, and 22 distances. Orbits were segmented. Registration-based, age-specific mean models were generated using semi-automatic segmentation, and aligned and compared using color-coded distance maps - mean absolute distance (MAD), Hausdorff distance (HD), and Dice similarity coefficient (DSC). Symmetry was assessed by mirroring and DSC computing. Central orbital depth (COD) and medial orbital depth (MOD) allowed 100% of orbits to be classified. COD and lateral orbital depth (LOD) were different from the controls. Average MAD between TCS and controls was ≤1.5 mm, while for HD it was >1.5 mm, and for DSC <1. TCS orbits were more asymmetrical than controls, and orbital volumes were smaller when age was considered as a confounding factor, and had a trend for normalization with age. This report emphasizes the importance of combining different morphometric approaches in the phenotype characterization of non-trivial structures such as the orbit, and supports composite skeletal and soft-tissue strategies for the management of the peri-orbital region.
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http://dx.doi.org/10.1016/j.jcms.2017.11.028DOI Listing
February 2018

Phenotypic spectrum of Tessier facial cleft number 5.

J Craniomaxillofac Surg 2018 Jan 27;46(1):22-27. Epub 2017 Oct 27.

Department of Maxillofacial and Plastic Surgery, National Reference Center for Cleft Lip and Palate, Hôpital Universitaire Necker-Enfants Malades, 149 rue de Sèvres, 75015, Paris, France; University Paris Descartes, 12 rue de l'Ecole de Médecine, 75006 Paris, France.

Introduction: Craniofacial clefts belong to the most disfiguring and rare congenital malformations of the face and among these, orbito-facial clefts constitute approximately 0.22 % of the cases with Tessier cleft number 5 being the least common. Our aim was to define the phenotypic spectrum for this subgroup to improve clinical management.

Methods: Our study group consisted of four patients which were treated at two different cleft centers. Retrospective chart review and anatomical analysis were conducted for each patient based on clinical evaluation and imaging studies. Morphological anomalies including soft tissue, bone and oral components were recorded.

Results: Based on our analysis and literature review, we could define two subtypes of Tessier facial cleft number 5. (1) Medial clefts are the more severe subtype, creating a significant soft tissue and bone defect that runs vertically, through the eyelid, infraorbital rim, maxillary sinus and cheek. They have the poorer esthetic and functional prognosis, due to orbital dystopia and absence of lower eyelid. (2) Lateral clefts are a less severe subtype characterized by the presence of a vertical furrow of the cheek running laterally to the maxillary sinus.

Conclusions: We identified two subtypes of facial cleft number 5 which require an individualized surgical management.
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http://dx.doi.org/10.1016/j.jcms.2017.10.012DOI Listing
January 2018

Prenatal Diagnosis of a Melanotic Neuroectodermal Tumor of Infancy (MNTI): A Case Report With a Favorable Outcome After Chemotherapy Failure and Incomplete Resection.

J Pediatr Hematol Oncol 2018 05;40(4):320-324

Unit of Plastic and Maxillofacial Surgery.

We present the case of a woman referred to our department at 34 weeks of pregnancy with a fetal ultrasonographic scan showing a mass that had developed within the right maxilla with invasion of the orbit. A retrospective examination showed that this tumor had been present since the 12th week of pregnancy. At 39+4 weeks of gestation, a boy was born. He presented a black firm aspect in the maxilla. A computed tomographic scan and magnetic resonance imaging revealed a soft tissue swelling over the right maxilla, extending into the orbit but without invasion of the globe. Surgical biopsy confirmed a melanotic neuroectodermal tumor of infancy. The pathologic examination did not show any neuroblast-like component on the hematoxylin eosin saffron staining. Because of the extension and the size of the lesion, neoadjuvant chemotherapy was carried out. At day 21, the patient received 1 cycle of low-dose cyclophosphamide and vincristine, 2 cycles of etoposide and carboplatin, and thereafter 1 cycle of cyclophosphamide, adriamycin, and vincristin because the lesion kept growing. After stabilization of the size of the tumor, at 4 months, a maxillectomy and partial resection of the orbital floor and lateral orbital wall was performed on the patient. As a complete resection would have required orbital exenteration, surgery was performed deliberately incomplete leaving a macroscopic residue (R2). At 2.5 years of follow-up, the patient showed complete remission with no lesions evident on magnetic resonance imaging.
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http://dx.doi.org/10.1097/MPH.0000000000000982DOI Listing
May 2018

Congenital Infantile Fibrosarcoma Associated With a Lipofibromatosis-Like Component: One Train May Be Hiding Another.

Am J Dermatopathol 2017 Jun;39(6):463-467

Departments of *Maxillofacial and Plastic Surgery, and †Pathology, Necker Children Hospital, APHP, Paris, France; ‡Paris Descartes University, Paris, France; Departments of §Pediatric Radiology, and ¶Dermatology, Necker Children Hospital, APHP, Paris, France; ‖Laboratory of Solid Tumors Genetics and Central Laboratory of Pathology, Nice University Hospital, Nice, France; **Microenvironment, Signaling and Cancer, INSERM, Université Nice Sophia-Antipolis, Nice, France; ††Molecular Oral Pathology, INSERM, Centre de Recherche de Cordeliers, Paris, France; and ‡‡Adolescent and Pediatric Oncology Department, Institut Curie, Paris, France.

Congenital infantile fibrosarcoma (CIFS) is a soft tissue sarcoma of infants mainly involving lower extremities and usually developing during the first year of life. At another end of the spectrum of pediatric fibroblastic lesions, lipofibromatosis is a rare benign infiltrative soft tissue tumor that affects children. The authors report in this study a particular presentation with a CIFS surrounded by lipofibromatosis-like areas. The presence of a surrounding benign tumor confused and delayed CIFS diagnosis.
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http://dx.doi.org/10.1097/DAD.0000000000000696DOI Listing
June 2017

Characteristics of defenestrating craniofacial injuries in pediatric patients.

Am J Emerg Med 2017 07 13;35(7):1027-1030. Epub 2017 Feb 13.

APHP, Necker Enfants Malades, Service de Chirurgie Maxillo-faciale et Chirurgie Plastique, 75015 Paris, France; Université Paris Descartes, 75005 Paris, France.

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http://dx.doi.org/10.1016/j.ajem.2017.02.023DOI Listing
July 2017

TMJ arthritis is a frequent complication of otomastoiditis.

J Craniomaxillofac Surg 2016 Dec 4;44(12):1984-1987. Epub 2016 Oct 4.

Université Paris Descartes, 75005 Paris, France; APHP, Necker Enfants Malades, Service de Chirurgie Maxillofaciale et Chirurgie Plastique, 75015 Paris, France. Electronic address:

Introduction: Septic arthritis of the temporomandibular joint (TMJ) is a rare condition known to result in significant morbidity if diagnosis is delayed. Acute otomastoiditis is a typical complication of acute otitis media but few cases of acute otomastoiditis complicated with TMJ arthritis have been reported in the international literature. Furthermore, otomastoiditis reports and studies rarely analyzed TMJ CT scans. The aim of this study was to determine the incidence of TMJ arthritis in acute otomastoiditis, based on the analysis of CT scans.

Materials And Methods: We conducted a prospective study from 2014 to 2015, including all consecutive pediatric patients admitted to the Pediatric Otolaryngology department for acute otomastoiditis. A craniofacial injected CT scan was performed in all patients. The imagery was prospectively blind analyzed by two independent investigators screening for the criteria of TMJ arthritis. Finally, during the long-term follow-up we noted the number of patients presenting a clinical TMJ ankylosis.

Results: We included 45 patients. The analysis showed 15 patients with TMJ effusion. Of those, 6 (13.33%) had an abscess and 2 clinical ankyloses.

Conclusion: This study showed a high rate of TMJ arthritis complicating otomastoiditis. Our results demonstrate that systematic TMJ analysis in the CT scan of patients with otomastoiditis is essential.
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http://dx.doi.org/10.1016/j.jcms.2016.09.015DOI Listing
December 2016

Reconstruction of a large calvarial traumatic defect using a custom-made porous hydroxyapatite implant covered by a free latissimus dorsi muscle flap in an 11-year-old patient.

J Neurosurg Pediatr 2017 Jan 28;19(1):51-55. Epub 2016 Oct 28.

Department of Neurosurgery, Necker Hospital, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.

Reconstruction of complex skull defects requires collaboration between neurosurgeons and plastic surgeons to choose the most appropriate procedure, especially in growing children. The authors describe herein the reconstruction of an extensive traumatic bone and soft tissue defect of the cranial vault in an 11-year-old boy. The size of the defect, quality of the tissues, and patient's initial condition required a 2-stage approach. Ten months after an initial emergency procedure in which lacerated bone and soft tissue were excised, reconstruction was performed. The bone defect, situated on the left frontoparietal region, was 85 cm and was filled by a custom-made porous hydroxyapatite implant. The quality of the overlying soft tissue did not allow the use of classic local and locoregional coverage techniques. A free latissimus dorsi muscle flap branched on the contralateral superficial temporal pedicle was used and left for secondary healing to take advantage of scar retraction and to minimize alopecia. Stable well-vascularized implant coverage as well as an esthetically pleasing skull shape was achieved. Results in this case suggest that concomitant reconstruction of large calvarial defects by cranioplasty with a custom-made hydroxyapatite implant covered by a free latissimus dorsi muscle flap is a safe and efficient procedure in children, provided that there is no underlying infection of the operative site.
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http://dx.doi.org/10.3171/2016.8.PEDS1653DOI Listing
January 2017

Defining a new aggressiveness classification and using NFATc1 localization as a prognostic factor in cherubism.

Hum Pathol 2016 12 3;58:62-71. Epub 2016 Aug 3.

INSERM, UMRS 1138, Centre de Recherche de Cordeliers, Molecular Oral Pathology, 75006 Paris, France; Université Paris Descartes, 75006 Paris, France; APHP, Necker Enfants Malades, Service de Chirurgie Maxillo-Faciale et Plastique, 75015 Paris, France; APHP, CRMR des Malformations Rares de la Face et de la Cavité Buccale, 75015 Paris, France.

Cherubism is a rare genetic disease characterized by bilateral giant cell reparative granuloma of the jaws consisting of a fibrotic stroma with giant multinucleated cells (GMCs) and osteoclastic features. Cherubism severity is highly variable, and recurrence after surgery is the most important risk. Currently, there are no prognostic indicators. The aims of this study were to evaluate the osteoclastogenesis phenotype by histologic examination of nuclear factor of activated T cells 1 (NFATc1) localization and tartrate-resistant acid phosphatase (TRAP) activity and to correlate the results to disease aggressiveness to define prognostic indicators. Based on cherubism evolution 1 year after surgery, 3 classes of cherubism aggressiveness were identified: mild (group A), moderate (group B), and severe (group C). Histologically, in grade A and B cherubism lesions, GMCs were negative for both TRAP activity and NFATc1 nuclear localization. In contrast, in grade C cherubism lesions, GMCs were all positive for TRAP activity and NFATc1 nuclear localization and displayed osteoclast-like features. Other histopathologic findings were not different among the 3 groups. Our results establish that TRAP activity and NFTAc1 nuclear localization are associated with aggressive cherubism and therefore could be added to routine pathologic examination to aid in prognosis and management of the disease. The finding of NFATc1 nuclear localization in aggressive tumors supports the addition of anticalcineurin treatment to the therapeutic arsenal for cherubism.
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http://dx.doi.org/10.1016/j.humpath.2016.07.019DOI Listing
December 2016