"Oris Duplicatio"-Duplication of the Oral Cavity a Rare Malformation in a 10-Month-Old Child: State of the Science and Management.

The authors report the case of a 10-month-old child with total oral duplication. The authors review this pathology and the diagnostic and treatment modality through the few cases described in scientific history. The discussed etiopathogeny of this rare malformation is detailed in this work.

Individual Response to Radiation of Individuals with Neurofibromatosis Type I: Role of the ATM Protein and Influence of Statins and Bisphosphonates.

Neurofibromatosis type 1 (NF1) is a disease characterized by high occurrence of benign and malignant brain tumours and caused by mutations of the neurofibromin protein. While there is an increasing evidence that NF1 is associated with radiosensitivity and radiosusceptibility, few studies have dealt with the molecular and cellular radiation response of cells from individuals with NF1. Here, we examined the ATM-dependent signalling and repair pathways of the DNA double-strand breaks (DSB), the key-damage induced by ionizing radiation, in skin fibroblast cell lines from 43 individuals with NF1. Ten minutes after X-rays irradiation, quiescent NF1 fibroblasts showed abnormally low rate of recognized DSB reflected by a low yield of nuclear foci formed by phosphorylated H2AX histones. Irradiated NF1 fibroblasts also presented a delayed radiation-induced nucleoshuttling of the ATM kinase (RIANS), potentially due to a specific binding of ATM to the mutated neurofibromin in cytoplasm. Lastly, NF1 fibroblasts showed abnormally high MRE11 nuclease activity suggesting a high genomic instability after irradiation. A combination of bisphosphonates and statins complemented these impairments by accelerating the RIANS, increasing the yield of recognized DSB and reducing genomic instability. Data from NF1 fibroblasts exposed to radiation in radiotherapy and CT scan conditions confirmed that NF1 belongs to the group of syndromes associated with radiosensitivity and radiosusceptibility.

First radiobiological characterization of the McCune-Albright syndrome: influence of the ATM protein and effect of statins + bisphosphonates treatment.

PURPOSE: MacCune-Albright syndrome (MAS) is a rare autosomal dominant osteo-hormonal disorder. MAS is characterized by a severe form of polyostotic fibrous dysplasia, 'café-au-lait' pigmentation of the skin and multiple endocrinopathies. MAS was shown to be caused by mosaic missense somatic mutations in the GNAS gene coding for the alpha-subunit of the stimulatory G-protein. MAS is also associated with radiation-induced malignant tumors, like osteosarcoma, fibrosarcoma and chondrosarcoma but their origin remains misunderstood. In parallel, bisphosphonates treatment was shown to improve the MAS patients' outcome, notably by increasing bone density but, again, the molecular mechanisms supporting these observations remain misunderstood. MATERIALS AND METHODS: Here, by using fibroblast and osteoblast cell lines derived from 2 MAS patients, the major radiobiological features of MAS were investigated. Notably, the clonogenic cell survival, the micronuclei and the γH2AX, pATM and MRE11 immunofluorescence assays were applied to MAS cells. RESULTS: It appears that cells from the 2 MAS patients are associated with a moderate but significant radiosensitivity, a delayed radiation-induced nucleoshuttling of the ATM kinase likely caused by its sequestration in cytoplasm, suggesting impaired DNA double-strand breaks (DSB) repair and signaling in both fibroblasts and osteoblasts. Such delay may be partially corrected by using bisphosphonates combined with statins, which renders cells more radioresistant. CONCLUSIONS: Our findings represent the first radiobiological characterization of fibroblasts and osteoblasts providing from MAS patients. Although the number of studied cases is reduced, our findings suggest that the MAS cells tested belong to the group of syndromes associated with moderate but significant radiosensitivity. Further investigations are however required to secure the clinical transfer of the combination of bisphosphonates and statins, to reduce the disease progression and to better evaluate the potential risks linked to radiation exposure.

Are Inferior Rectus Muscle Displacement and the Fracture's Size Associated With Surgical Repair Decisions and Clinical Outcomes in Patients With Pure Blowout Orbital Fracture?

PURPOSE: Although orbital blowout fractures are common, there is no consensus with respect to treatment decision making and long-term outcome. The purpose of this study was to evaluate the association between inferior rectus muscle (IRM) displacement and fracture size and the surgical repair decisions and clinical outcomes in patients with blowout fractures (BOFs). PATIENTS AND METHODS: We designed a prospective cohort study and enrolled all patients who presented to the University Hospital of Geneva for evaluation of a BOF. The primary predictor variables were the IRM grade, measuring the severity of downward displacement of the IRM relative to the level of the fracture's edge (mild [grade I], moderate [grade II], or severe [grade III]), and fracture size. The primary outcome was surgical repair. The secondary outcomes were post-trauma diplopia (at baseline and at 10 days) and persistent annoying diplopia and/or enophthalmos considered independently or as a composite outcome. Other study variables included demographic and injury-related parameters. Descriptive, bivariate, and multiple logistic regression statistics were computed, and the significance level was set at P ≤ .05. RESULTS: The sample was composed of 108 patients with a mean age of 46.8 ± 23 years; 73.1% were men. The IRM grade was associated with surgical repair (P < .001), post-trauma diplopia (P < .001), and the composite outcome (P = .003). Fracture size was associated with enophthalmos (P = .03) and the composite outcome (P = .009). In the adjusted model, only IRM grades II and III were associated with the decision for surgical repair (P < .001). CONCLUSIONS: The results of this study suggest that the IRM grade, unlike fracture size, may be a valid measurement in surgical decision making, as well as in determining BOF severity, as evidenced by the correlation between the IRM grade and surgical repair, as well as clinical outcome.

Some mutations in the xeroderma pigmentosum D gene may lead to moderate but significant radiosensitivity associated with a delayed radiation-induced ATM nuclear localization.

Purpose: Xeroderma Pigmentosum (XP) is a rare, recessive genetic disease associated with photosensitivity, skin cancer proneness, neurological abnormalities and impaired nucleotide excision repair of the UV-induced DNA damage. Less frequently, XP can be associated with sensitivity to ionizing radiation (IR). Here, a complete radiobiological characterization was performed on a panel of fibroblasts derived from XP-group D patients (XPD).Materials and methods: Cellular radiosensitivity and the functionality of the recognition and repair of chromosome breaks and DNA double-strand breaks (DSB) was evaluated by different techniques including clonogenic cell survival, micronuclei, premature chromosome condensation, pulsed-field gel electrophoresis, chromatin decondensation and immunofluorescence assays. Quantitative correlations between each endpoint were analyzed systematically.Results: Among the seven fibroblast cell lines tested, those derived from three non-relative patients holding the p.[Arg683Trp];[Arg616Pro] XPD mutations showed significant cellular radiosensitivity, high yield of residual micronuclei, incomplete DSB recognition, DSB and chromosome repair defects, impaired ATM, MRE11 relocalization, significant chromatin decondensation. Interestingly, XPD transduction and treatment with statins and bisphosphonates known to accelerate the radiation-induced ATM nucleoshuttling led to significant complementation of these impairments.Conclusions: Our findings suggest that some subsets of XPD patients may be at risk of radiosensitivity reactions and treatment with statins and bisphosphonates may be an interesting approach of radioprotection countermeasure. Different mechanistic models were discussed to better understand the potential specificity of the p.[Arg683Trp];[Arg616Pro] XPD mutations.

Recurrent Maxillary Sinusitis and Periorbital Cellulitis Revealing an Unnoticed Medial Wall Orbital Fracture.

Unilateral recurrent maxillary sinusitis is a common sinunasal pathology, mostly related to the ostiomeatal complex dysfunction. Although sinusitis can potentially spread to the adjacent structures, orbital cellulitis remains an exceptionally rare sequela.The authors report the unusual case of a patient who presented with recurrent maxillary sinusitis complicated by cyclic episodes of periorbital cellulitis related to ostiomeatal complex obstruction from herniated periorbital fat through an unnoticed medial orbital wall fracture. To the best of our knowledge, no other similar case has previously been reported. The possible explanation for such an unusual association is discussed.

[Short osteotomy use in orthognathic surgery: benefit, disadvantage and perspective]. / La place de l'ostéotomie courte en chirurgie orthognathique : avantages, inconvénients et perspectives.

INTRODUCTION:  The short osteotomy was first reported by Blair in 1907 and was later described and characterized by Kater and Paulus in 2013. The technique involves an oblique supra-lingular osteotomy from internal to external, from top to bottom and from back to front. It is designed to divide the ramus into two segments, the joint and the mandibular body, and to ensure minimal valve equivalents. Both osseous valves were maintained in contact by obtaining surface contact proportional to the angle of the osteotomy. MATERIALS AND METHODS:  We present a series of 82 patients to demonstrate the benefits of this technique in terms of stability and conservation of sensitivity. RESULTS:  82 patients were included, of which 74 (90%) described normal sensitivity and 8 (10%) reported modified sensitivity two years post-surgery. DISCUSSION:  On account of the nature and height of the short osteotomy cut, it is possible to avoid direct manipulation of the lower alveolar nerve. The postoperative sensitivity level is identical to the pre-operative level in more than 90% of cases. In good indications, this technique could be used preferentially to optimize postoperative nerve recovery. We also discuss the current limitations of this orthognathic surgery procedure, as well as the perspectives linked to the development of 3D printing and preoperative planning.

Orbital Reconstruction by Patient-Specific Implant Printed in Porous Titanium: A Retrospective Case Series of 12 Patients.

PURPOSE: The purpose of this study was to evaluate the orbital patient-specific implant (PSI) directly printed in porous titanium for the reconstruction of complex orbital bone defects in a series of 12 patients. PATIENTS AND METHODS: The authors designed and implemented a case series. The sample consisted of patients with unilateral complex orbital bone loss. All patients received a porous titanium PSI designed from the healthy contralateral side (mirroring). The criteria analyzed were the functional results: correction of enophthalmos, correction of ocular motility, operative time, complications, and operative revisions. The study was performed from 2015 through 2017. RESULTS: The sample was composed of 12 patients (mean age, 47 yr; age range, 13 to 70 yr). Patients were followed for a mean of 36 weeks postoperatively (range, 4 to 100 weeks). Twelve of the 12 patients presented preoperative enophthalmia, and 8 of the 12 patients presented preoperative diplopia. The mean operating time was 71 minutes (range, 60 to 200 minutes). For 8 patients, the follow-up was simple. In contrast, 2 patients required surgical revision with repositioning of the implant because of intraoperative implant malpositioning with esthetic or functional disturbance and malpositioning was confirmed on the postoperative computed tomogram, 1 patient required explantation of his implant 7 months after the surgery because of spheno-orbital meningioma recurrence (the implant was well positioned), and 1 patient operated on by a subciliary approach presented a postoperative ectropion. In this series of porous titanium orbital PSIs without positioning guides, 17% had malpositioning (2 patients who required a new intervention for repositioning). CONCLUSION: The results of this study suggest that porous titanium PSI could be a surgical option for patients with complex orbital bone defects. In this series 17% of the sample needed a second operation. There are several ways to improve these results, such as intraoperative navigation or integrated positioning guides.

Orbital Cavernous Hemangioma Causing Spontaneous Compressive Hemorrhage.

Cavernous hemangiomas are the most common tumors of the posterior cone of the orbit in adults. They are discovered in a fortuitous manner or in front of the appearance of a progressive exophthalmia.The authors report through a complete literature review (PubMed) patients of retro-orbital cavernous hemangioma revealed by spontaneous compressional hemorrhage from 1984 to 2017.This review is illustrated by a case of sharp decrease in visual acuity secondary to orbital cavernous hemangioma hemorrhage.The authors detail the management and the evolution of all these patients.

Radiobiological Characterization of Tuberous Sclerosis: a Delay in the Nucleo-Shuttling of ATM May Be Responsible for Radiosensitivity.

The tuberous sclerosis complex (TSC) syndrome is associated with numerous cutaneous pathologies (notably on the face), epilepsy, intellectual disability and developmental retardation and, overall, high occurrence of benign tumors in several organs, like angiofibromas, giant cell astrocytomas, renal angiomyolipomas, and pulmonary lymphangioleiomyomatosis. TSC is caused by mutations of either of the hamartin or tuberin proteins that are mainly cytoplasmic. Some studies published in the 1980s reported that TSC is associated with radiosensitivity. However, its molecular basis in TSC cells is not documented enough. Here, we examined the functionality of the repair and signaling of radiation-induced DNA double-strand breaks (DSB) in fibroblasts derived from TSC patients. Quiescent TSC fibroblast cells elicited abnormally low rate of recognized DSB reflected by a low yield of nuclear foci formed by phosphorylated H2AX histones. Irradiated TSC cells also presented a delay in the nucleo-shuttling of the ATM kinase, potentially due to a specific binding of ATM to mutated TSC protein in cytoplasm. Lastly, TSC fibroblasts showed abnormally high MRE11 nuclease activity suggesting genomic instability. A combination of biphosphonates and statins complemented these impairments by facilitating the nucleoshuttling of ATM and increasing the yield of recognized DSB. Our results showed that TSC belongs to the group of syndromes associated with low but significant defect of DSB signaling and delay in the ATM nucleo-shuttling associated with radiosensitivity.

Giant Hemifacial Fibrous Dysplasia Functional Treatment and Place of Pamidronate.

The authors report the case of a 9-year-old child with severe form of hemifacial fibrous dysplasia. The authors review the pathology of this treatment modality through the case description and detail the place of pamidronate in the treatment of fibrous dysplasia.

Costal Grafting in Mandibular Reconstruction.

BACKGROUND: Reconstruction of mandibular bone defect is a common indication in craniomaxillofacial surgery, and free fibular flap is the gold standard for this indication. However, there are alternatives; nonvascular bone grafting is one of them, and we present the costal grafting for mandibular reconstruction, a classic technique that is reliable, efficient, and produced less morbidity than the technique of using composite free flaps. METHOD: A 9-year retrospective review of 54 patients treated surgically for mandibular reconstruction was performed. The criterion mainly analyzed was graft survival. The surgical technique was described in detail. RESULTS: A total of 54 patients with mandibular bone defect were identified. Five symphysis, 46 corpus, and 20 ramus defects were considered. These patients underwent reconstruction by costal grafting, and the engrafting was successful in 92.6% of cases. Dental rehabilitation with dental implants was realized in 70% of cases. CONCLUSIONS: The approach described in this article allowed the authors to obtain good results with costal grafting for mandibular reconstruction and dental rehabilitation. Costal grafting is a good alternative for fibula free flap in specific indications. Reconstruction of mandibular bone defect is a common indication in craniomaxillofacial surgery. Since the 1980s, the gold standard for these defects is the use of free fibular flap.(1) In some cases, this technique is contradicted; the surgeon then has several possibilities for the use of free osteomyocutaneous flaps (iliac crest, scapula, and serrato-costal flaps).(2-8).

Superior eyelid crease approach for transobital neuroendoscopic surgery of the anterior cranial fossa.

Access to the anterior cranial fossa has traditionally required a large exposure of the surgical field, which can be a source of aesthetic and neurologic morbidity. Minimally invasive surgery approaches have been developed to overcome these adverse effects and was, for a long time, represented by endonasal endoscopic surgery. The superior eyelid crease approach of the anterior cranial fossa with supraorbital osteotomy was described in the early 80s as an interesting alternative to the endonasal approach. This keyhole endoscopic approach allows safe and efficient surgery of the orbit, the anterior cranial fossa, and the mesiotemporal lobe. We successfully treated 10 patients with benign tumors of the anterior cranial fossa, with excellent cosmetic results and no complications. This study presents the surgical technique and its potential indication and limits throughout our experience as well as a review of the literature.