Patrick Goudot

Mandibular cuniculatum carcinoma: Apropos of 3 cases and literature review

Cuniculatum carcinoma is a well‐differentiated form of squamous cell carcinoma that shares histologic characteristics with papillary squamous cell carcinoma and verrucous carcinoma. Cuniculatum carcinoma usually occurs on the plantar region, and only 16 cases involving the oral cavity have been described in the literature.

Clinical relevance of systematic human papillomavirus (HPV) diagnosis in oral squamous cell carcinoma

Head & Neck Cancer (HNC) is one of the most common malignancies worldwide and among oral neoplasias about 90-92% are squamous cell carcinomas (OSCC). Alcohol and tobacco consumption have been recognized as the main risk factors for development of OSCC. However, 10 to 20% of patients suffering from OSCC have no history of use of these substances. Clinico-pathological evidence suggests that we are dealing with virally-induced cancers, and that HPV should not be a relevant candidate. A systematic search of HPV in OSCC has no real relevance in current clinical practice even although it is still relevant in organized research protocols. Further studies are ongoing, with the aim of identifying other infectious agents, including viruses, in OSCC.

The dynamics of gene expression changes in a mouse model of oral tumorigenesis may help refine prevention and treatment strategies in patients with oral cancer

A better understanding of the dynamics of molecular changes occurring during the early stages of oral tumorigenesis may help refine prevention and treatment strategies. We generated genome-wide expression profiles of microdissected normal mucosa, hyperplasia, dysplasia and tumors derived from the 4-NQO mouse model of oral tumorigenesis. Genes differentially expressed between tumor and normal mucosa defined the “tumor gene set” (TGS), including 4 non-overlapping gene subsets that characterize the dynamics of gene expression changes through different stages of disease progression. The majority of gene expression changes occurred early or progressively. The relevance of these mouse gene sets to human disease was tested in multiple datasets including the TCGA and the Genomics of Drug Sensitivity in Cancer project. The TGS was able to discriminate oral squamous cell carcinoma (OSCC) from normal oral mucosa in 3 independent datasets. The OSCC samples enriched in the mouse TGS displayed high frequency of CASP8 mutations, 11q13.3 amplifications and low frequency of PIK3CA mutations. Early changes observed in the 4-NQO model were associated with a trend toward a shorter oral cancer-free survival in patients with oral preneoplasia that was not seen in multivariate analysis. Progressive changes observed in the 4-NQO model were associated with an increased sensitivity to 4 different MEK inhibitors in a panel of 51 squamous cell carcinoma cell lines of the aerodigestive tract. In conclusion, the dynamics of molecular changes in the 4-NQO model reveal that MEK inhibition may be relevant to prevention and treatment of a specific molecularly-defined subgroup of OSCC.

Kératokystes (ou tumeurs odontogéniques kératokystiques)

The aim of this study was to describe the management of keratocysts based on our own experience and on a large literature review. Keratocysts are benign odontogenic epithelial tumors. The main aspects of this lesion are described (definition, epidemiology, clinic, radiology, histology, treatment, and prognosis). In small intra-osseous tumors, surgical procedure must be as conservative as possible, most often enucleation. In large tumors with destruction of the cortical bone, or with destruction of coronoid process or notch, extensive resection can be indicated, with sometimes a transfacial approach for an accurate control, especially in soft tissues. Strict follow-up is mandatory because of the high risk of recurrence.

The promising impact of molecular profiling on treatment strategies in oral cancers

Oral squamous cell carcinoma (OSCC) is a major cause of cancer-associated morbidity and mortality. Although OSCC may develop from easily accessible oral preneoplastic lesions (OPLs), no intervention has been reported so far that reduces the rate of malignant transformation. A comprehensive molecular characterization of oral carcinogenesis may help refining treatment strategies both in patients with OPLs and OSCC. Herein, we review main molecular alterations occurring at different steps during oral carcinogenesis and show how molecularly-based medicine and surgery may impact the outcome of OSCC in the future.

A 13-gene expression-based radioresistance score highlights the heterogeneity in the response to radiation therapy across HPV-negative HNSCC molecular subtypes

BackgroundRadiotherapy for head and neck squamous cell carcinomas (HNSCC) is associated with a substantial morbidity and inconsistent efficacy. Human papillomavirus (HPV)-positive status is recognized as a marker of increased radiosensitivity. Our goal was to identify molecular markers associated with benefit to radiotherapy in patients with HPV-negative disease.MethodsGene expression profiles from public repositories were downloaded for data mining. Training sets included 421 HPV-negative HNSCC tumors from The Cancer Genome Atlas (TCGA) and 32 HNSCC cell lines with available radiosensitivity data (GSE79368). A radioresistance (RadR) score was computed using the single sample Gene Set Enrichment Analysis tool. The validation sets included two panels of cell lines (NCI-60 and GSE21644) and HPV-negative HNSCC tumor datasets, including 44 (GSE6631), 82 (GSE39366), and 179 (GSE65858) patients, respectively. We finally performed an integrated analysis of the RadR score with known recurrent genomic alterations in HNSCC, patterns of protein expression, biological hallmarks, and patterns of drug sensitivity using TCGA and the E-MTAB-3610 dataset (659 pancancer cell lines, 140 drugs).ResultsWe identified 13 genes differentially expressed between tumor and normal head and neck mucosa that were associated with radioresistance in vitro and in patients. The 13-gene expression-based RadR score was associated with recurrence in patients treated with surgery and adjuvant radiotherapy but not with surgery alone. It was significantly different among different molecular subtypes of HPV-negative HNSCC and was significantly lower in the “atypical” molecular subtype. An integrated analysis of RadR score with genomic alterations, protein expression, biological hallmarks and patterns of drug sensitivity showed a significant association with CCND1 amplification, fibronectin expression, seven hallmarks (including epithelial-to-mesenchymal transition and unfolded protein response), and increased sensitivity to elesclomol, an HSP90 inhibitor.ConclusionsOur study highlights the clinical relevance of the molecular classification of HNSCC and the RadR score to refine radiation strategies in HPV-negative disease.

Three-dimensional reconstructions of CT scans and cone beam CT of impacted maxillary canines in order to locate areas of ankylosis before orthodontic traction

PURPOSE The aim of this study was to model impacted maxillary canines and determine whether areas of ankylosis were present before undertaking orthodontic traction. MATERIAL AND METHODS Amira/ResolveRT™ software, version 5.0, by FEI Company is a meshing and surface-rendering program that was used to produce three-dimensional reconstructions from CT scans and cone beam images of the impacted canines of 30 patients (10 cone beam files and 20 CT scan files). RESULTS AND DISCUSSION The presence of zones of ankylosis on the roots of certain impacted canines is revealed by the inversion of the direction of meshing on the tooth surface and on a larger scale by invagination of bone tissue into the tooth tissue at various densities measured in Hounsfield units by the AMIRA™ software program. This observation can guide treatment towards extraction of the impacted tooth, its autotransplantation, or deep alveolar corticotomy, followed by mobilization when the canine is in a vestibular position. CONCLUSION AMIRA™ software made it possible to detect zones of ankylosis on the roots of certain impacted canines and to adopt a treatment program different from conventional surgico-orthodontic traction. The final aim is to reposition the impacted canine without endangering the adjacent teeth.

Ingénierie tissulaire et chirurgie maxillofaciale. Compte-rendu de la réunion du samedi 10 janvier 2015 – La Pitié-Salpêtrière – Paris

C’est la prise de conscience double que nombre d’équipes de chirurgie maxillofaciale françaises étaient investies dans l’ingénierie tissulaire et que celle-ci, orientée vers l’os, le cartilage et les dents, trouvait des applications naturelles en chirurgie de l’extrémité céphalique, qui a suscité, à l’initiative du Professeur Goudot, une première réunion le 10 janvier 2015 dans les locaux du service de chirurgie maxillofaciale de La-Pitié-Salpêtrière. Croiser les expériences de chacun, faire se croiser les collègues fondamentalistes et cliniciens impliqués, dégager une « ligne disciplinaire », tels étaient les attendus. Amiens, Besançon, Caen, Dijon, Montpellier, Nantes, Paris, Strasbourg étaient les villes représentées (Lille et Marseille étaient excusées). C’est dans cet ordre alphabétique qu’elles se présentèrent sous l’œil expert du Professeur Jérôme Larghero (unité de biothérapie, hôpital Saint-Louis, AP–HP). Marolleau (IFF) et sur la collaboration avec l’UTC du Professeur Cécile Legallais, l’équipe amiénoise (B. Devauchelle, S. Testelin, L. Garcon) fait état de deux projets structurants financés (Vascos, Ingetisos) et du projet déposé (Intim) concernant le tissu osseux. Ce dernier vise à mettre au point un tissu hybride bicouche à partir de cellules souches mésenchymateuses, l’une tournée vers la perte de substance osseuse, l’autre vers le muscle tissu cellulaire sous-cutané. Dans le même esprit est présenté le travail de recherche du Docteur Andréas Mueller (Bâle) et du Docteur Alexandre Caula, sur un modèle de fentes palatines et les essais d’utilisation d’une matrice d’alginate de calcium (partenariat industriel). En parallèle est fait état du projet Silkguide, mené avec l’UTC sur la régénération nerveuse sur guide de soie (Professeur Egles). Dans sa présentation, Loı̈c Garçon a insisté sur les facteurs influençant l’expression génique des gênes Run X2 dans la différenciation ostéoblastique. L’équipe de Besançon (A. Louvrier) a présenté, en collaboration avec le laboratoire de biologie cellulaire de l’université de Franche-Comté (EA 4268, SFR FED 4234 – L. Nicod), le centre d’investigation clinique en innovation technologique du CHU de Besançon (Inserm CIT 808 – Dr L. Pazart), le laboratoire intervention, innovation, imagerie, ingénierie en santé de l’université de Franche-Comté (EA 4268 – B. Kastler), l’unité Inserm U595 de l’université de Strasbourg (F. Meyer) et l’unité Inserm UMR 957 de l’université de Nantes (P. Layrolle), son axe de recherche financé Pulp’R destiné à évaluer, in vitro, les capacités d’ensemencement par des cellules souches d’origine pulpaire d’un scaffold innovant, les possibilités de différentiation de ces cellules en odontoblastes et les possibilités de régénération du complexe pulpodentinaire de la dent en contre-point des traitements endodontiques actuels. L’équipe de Caen (A. Veyssiere) a présenté, en collaboration avec l’EA 4652 (microenvironnement cellulaire et pathologies Milpat), animé par le Professeur Boumedienne, son axe de recherche Cartilage oreille et orifice nasal (Cartoon) destiné à comparer les caractéristiques morphologique, biochimique et immuno-histochimique des cartilages auriculaire et nasal chez les nourrissons porteurs de fentes labio-alvéolopalatines, le but

Dysosmies et dysgueusies post-traumatiques : aspects médicolégaux

The impact of anosmia or ageusia may be considerable for some occupations. Expert assessment shows how difficult it is to prove the diagnosis. A specialist is usually needed to demonstrate the asserted disorder. Damage compensation is based on the patients occupation and coverage.