Alterations in NO- and PGI2- dependent function in aorta in the orthotopic murine model of metastatic 4T1 breast cancer: relationship with pulmonary endothelial dysfunction and systemic inflammation.

BACKGROUND: Patients with cancer develop endothelial dysfunction and subsequently display a higher risk of cardiovascular events. The aim of the present work was to examine changes in nitric oxide (NO)- and prostacyclin (PGI2)-dependent endothelial function in the systemic conduit artery (aorta), in relation to the formation of lung metastases and to local and systemic inflammation in a murine orthotopic model of metastatic breast cancer. METHODS: BALB/c female mice were orthotopically inoculated with 4T1 breast cancer cells. Development of lung metastases, lung inflammation, changes in blood count, systemic inflammatory response (e.g. SAA, SAP and IL-6), as well as changes in NO- and PGI2-dependent endothelial function in the aorta, were examined 2, 4, 5 and 6 weeks following cancer cell transplantation. RESULTS: As early as 2 weeks following transplantation of breast cancer cells, in the early metastatic stage, lungs displayed histopathological signs of inflammation, NO production was impaired and nitrosylhemoglobin concentration in plasma was decreased. After 4 to 6 weeks, along with metastatic development, progressive leukocytosis and systemic inflammation (as seen through increased SAA, SAP, haptoglobin and IL-6 plasma concentrations) were observed. Six weeks following cancer cell inoculation, but not earlier, endothelial dysfunction in aorta was detected; this involved a decrease in basal NO production and a decrease in NO-dependent vasodilatation, that was associated with a compensatory increase in cyclooxygenase-2 (COX-2)- derived PGI2 production. CONCLUSIONS: In 4 T1 metastatic breast cancer in mice early pulmonary metastasis was correlated with lung inflammation, with an early decrease in pulmonary as well as systemic NO availability. Late metastasis was associated with robust, cancer-related, systemic inflammation and impairment of NO-dependent endothelial function in the aorta that was associated with compensatory upregulation of the COX-2-derived PGI2 pathway.

Nuclear accumulation of anthracyclines in the endothelium studied by bimodal imaging: fluorescence and Raman microscopy.

Anthracycline antibiotics display genotoxic activity towards cancer cells but their clinical utility is limited by their cardiac and vascular toxicity. The aim of this study was to develop a Raman-based methodology to study the nuclear accumulation of anthracyclines in the endothelium. For this purpose bimodal confocal Raman and fluorescence imaging was used to monitor cellular composition changes as a result of anthracycline exposure on endothelial cells (EA.hy926), and nuclear drug accumulation, respectively. Simultaneously effects of anthracyclines on endothelium viability were investigated by caspases-3 and -7 and MTT assays. We demonstrated that nuclear accumulation of DOX and EDOX was similar; however, EDNR accumulated in endothelial nuclei at concentrations 10 times higher than DNR. In turn, epimers of DOX or DNR were both consistently less toxic on the endothelium as compared to their congeners as evidenced by MTT and caspase assays. In summary, bimodal Raman and fluorescence-based nucleus profiling proves to be a valuable tool to study structure-activity relationship of nuclear accumulation and toxicity of anthracyclines in endothelium.

[Improvement of maxillofacial bone distraction osteogenesis: future prospects]. / Potentialisation de la distraction ostéogénique maxillofaciale, voies d'avenir.

Distraction osteogenesis is a tissue engineering technique based on Ilizarov's study on long bones. McCarthy transposed it rapidly to facial bones. His results in cranial and maxillofacial surgery are good and reproducible. However, the current protocols are long and the devices used are bulky. Finding new devices and association with other tissue engineering techniques should improve distraction osteogenesis and the patient's comfort.

Twenty-four years of experience in management of complex mandibular fractures with low cost, custom-made mandibular external fixation: A 65-patient series.

INTRODUCTION: Ginestet introduced the first external device used to fix the mandible in 1936. In 1949, Morris introduced a biphasic fixation device. This "Joe Hall Morris fixation" design led to use of a self-crafted external fixator based on pins connected by a breathing tube filled with dental resin. The objective of this study was to present our surgical results with this device through a 65-patient series. METHODS: This retrospective study included all the patients who benefited from the self-crafted mandibular external fixator at our Oral and Maxillofacial department from 1995 to 2019. Sixty-five patients were allocated into two groups. There were 39 patients in the temporary stabilisation (TS) group and 26 in the bone healing (BH) group. Functional criteria were investigated, including mouth opening limitations and occlusal abnormalities. Aesthetic evaluation focused on skin healing, evaluated by both surgeon and patient. RESULTS: Twenty-three patients exhibited spontaneous bone healing during their immobilisation period and two patients developed a pseudoarthrosis in the BH group. Most TS group patients benefited from secondary management by bone graft, bone free flap, or distraction osteogenesis. Few complications were noted with our technique during the study period. CONCLUSION: Our self-crafted external fixation with Joe Hall Morris fixation style is a valuable option for external stabilisation of the lower third of the face.

[Hypodontia: therapeutic strategy elaborated from 30 cases]. / L'oligodontie: stratégie thérapeutique à partir de 30 cas.

INTRODUCTION: Hypodontia is defined as the absence of at least six permanent teeth due to the hypodevelopment of tooth germs. The prevalence is weak and varies according to the ethnic origin. This familial abnormality is due to various mutations or polymorphisms of genes. It may be associated with other dental abnormalities. In children, it is responsible for growth, mastication, and phonation disorders, hypo-alveolia and lingual interposition in the toothless sites. We report the management of 30 patients presenting with oligodontia. MATERIAL AND METHOD: The diagnosis was made on clinical and paraclinical data. The vertical and transversal facial dimensions, the three facial proportions, labial morphology, the number and localization of teeth, and occlusion were analyzed for future orthognathic and implant rehabilitation. The occlusion was studied transversally and vertically on dental casts. Rehabilitation with implant supported dental prostheses was chosen when conditions were met. The therapeutic protocol could include up to four chronological phases: the early prosthetic phase, the orthodontic phase, the surgical phase, and the implant and prosthetic phase. RESULTS: The 30 patients' age (13 male and 17 female patients) ranged from six to 20 years. An average of 15 dents were missing (6 to 28). Except for one case, all the third molars were missing. In 66% of the cases, the second molar was missing, in 33% for the first molar. In 66% of the cases, two lateral maxillary incisors were missing. There were no premolars in 50% of the patients. Agenesis of premolars and molars induced posterior bone insufficiency in the mandibula. Dysmorphosis was always present with vertical growth disorders. Six patients were not given orthodontic treatment because they did not have enough teeth. Orthognathic surgery was used in 14 cases (46.7%). Seventeen patients (56.7%) underwent apposition graft. In three patients, a high position of the alveolar nerve required nerve derivation. Implants were inserted in 14 patients (46.7%). The total number of implants was 155. DISCUSSION: Rehabilitation with implant supported dental prostheses is a good treatment for oligodontia. It requires an interdisciplinary approach (including a maxillo-facial surgeon, an orthodontist, a dentist, and a prosthesis specialist). The patient's motivation as well as that of his family is crucial.

Catalytic activity of certain antibodies as a potential tool for drug synthesis and for directed prodrug therapies.

Catalytic activity of certain antibodies was proposed by Linus Pauling for the very first time more than six decades ago. Since then few examples of catalytic antibodies (abzymes) were found in human organism. From late 80's many synthetic abzymes were obtained after immunization by Transition State Analogs (TSA). Another approach is based on functional mimicry of antibody to an active site of an enzyme. Detection of an abzymatic activity requires special immunoassays. This unique strategy can be employed for new methods of drug synthesis, as well as for in vivo therapies. Catalytic antibodies seem to be a promising tool for therapeutic purposes, because of their specifity and stereoselectivity.

Functional and morphologic outcomes of CAD/CAM-assisted versus conventional microvascular fibular free flap reconstruction of the mandible: A retrospective study of 25 cases.

INTRODUCTION: Mandibular reconstruction using fibula free flap has been improved in the last decade with computer-aided design and computer-aided manufacturing (CAD/CAM) but any functional and aesthetic evaluation of their reattempts has been realized. Aim of this retrospective study is to compare functional and morphologic outcomes after mandibular reconstruction with fibula free flap using CAD/CAM or conventional peroperative shaping for mandible reconstruction. Moreover, we compared quality of life, patient and surgery characteristics in the two groups. PATIENTS AND METHODS: We realized a monocentric retrospective analyzed of 25 cases of unilateral mandibular reconstruction divided in two groups, using CAD/CAM (12 patient) or conventional approach (13 patients) between April 2012 and March. Functional and aesthetic measurements were performed postoperatively. RESULTS: Mouth opening, laterotrusion and protrusion of the mandible seemed to be improved in CAD/CAM group compared with conventional group but did not differ significantly. Quality of life, bite force, masticatory ability, eating and chewing satisfaction, appearance and social activity satisfaction did not differ significantly in the two groups. CONCLUSION: Even if no superiority has been established for CAD/CAM group regarding functional and aesthetic outcomes, a prospective design of future studies and transdisciplinary approach should improve our data and their interpretations. Thus, the integration of virtual planning and guided surgery is definitely of significant value and must be considered in complex maxillofacial reconstructions.

Influence of preoperative imaging on fibula free flap harvesting.

INTRODUCTION: The fibula free flap (FFF) is the gold standard for the reconstruction of large maxillofacial defects. Magnetic resonance angiography (MRA) seems to supersede digital subtraction angiography (DSA) as the reference in preoperative evaluation, being non-invasive and having equivalent diagnostic results. The aim of this study was to assess the impact of preoperative MRA versus DSA on the viability of FFF and its success rate. MATERIAL AND METHODS: A total of 216 patients, who underwent mandibular or maxillary FFF reconstruction from January 1995 to January 2011, were retrospectively included in the study. Of them, 101 patients underwent preoperative DSA and 115 underwent MRA. Recorded criteria were as follows: age, sex, tobacco consumption, defect etiology, preoperative vascular assessment, donor-site choice and flap failure. The DSA group was compared to the MRA group. RESULTS: The harvested side was switched in 15.7% of cases with preoperative MRA versus 4% with DSA. Our success rate was higher (96.1%) with MRA than with DSA (88.1%) (P<0.05). More atherosclerotic patients (P=0.004) were diagnosed through MRA. MRA and DSA showed similar results in anatomical variation detection. CONCLUSION: MRA is less invasive and more effective in atherosclerosis detection than DSA. Therefore, donor-site switching was more frequent in the MRA group, which led to a better success rate. MRA should replace DSA as the reference in preoperative assessment.

Ameloblastoma of the jaws: Management and recurrence rate.

INTRODUCTION: Ameloblastoma is a rare, benign odontogenic tumour associated with a high recurrence rate. It accounts for 1% of all tumours of the jaws. The purpose of this study was to compare the ameloblastoma recurrence rate according to the type of treatment: radical or conservative. PATIENTS AND METHODS: All patients with a diagnosis of ameloblastoma between 1991 and 2013 were retrospectively identified in order to extract topographic, radiological, and histological data and the type of treatment: conservative (marsupialization, enucleation, curettage) or radical (segmental resection) and to compare the recurrence rate according to the type of treatment. RESULTS: Twenty-seven patients were included, managed by conservative treatment (CT) in 22 cases and radical treatment (RT) in 14 cases. The recurrence rate was 90.9% in the CT group and 9.1% in the RT group (P=0.025) with a mean follow-up of 56.2 months. DISCUSSION: The recurrence rate after conservative treatment was higher than that after radical treatment. These results are similar to those reported in the literature. The choice of treatment must be adapted to the macroscopic and histological characteristics of each tumour and to the patient.

Mandibular reconstruction after cancer: an in-house approach to manufacturing cutting guides.

The restoration of mandibular bone defects after cancer can be facilitated by computer-assisted preoperative planning. The aim of this study was to assess an in-house manufacturing approach to customized cutting guides for use in the reconstruction of the mandible with osteocutaneous free flaps. A retrospective cohort study was performed, involving 18 patients who underwent mandibular reconstruction with a fibula free flap at three institutions during the period July 2012 to March 2015. A single surgeon designed and manufactured fibula and mandible cutting guides using a computer-aided design process and three-dimensional (3D) printing technology. The oncological outcomes, production parameters, and quality of the reconstructions performed for each patient were recorded. Computed tomography scans were acquired after surgery, and these were compared with the preoperative 3D models. Eighteen consecutive patients with squamous cell carcinoma underwent surgery and then reconstruction using this customized in-house surgical approach. The lengths of the fibula bone segments and the angle measurements in the simulations were similar to those of the postoperative volume rendering (P=0.61). The ease of access to 3D printing technology has enabled the computer-aided design and manufacturing of customized cutting guides for oral cancer treatment without the need for input from external laboratories.

Magnetic resonance imaging and computed tomography in the assessment of mandibular invasion by squamous cell carcinoma of the oral cavity. Influence on surgical management and post-operative course.

INTRODUCTION: Preoperative evaluation of the bone for invasion by oral cavity squamous cell carcinoma remains challenging. The aim of our study was to compare the accuracy of MRI and CT in detecting mandibular invasion by oral squamous cell carcinoma of the oral cavity, with histologic results as the reference standard, and to assess the influence on surgical management and post-operative course. PATIENTS AND METHODS: Patients who were clinically suspected of having bone invasion from oral cavity carcinoma were retrospectively included. A single senior radiologist reviewed MRI images and CT-scans, independently, for the presence or absence of mandibular invasion. The different surgical procedures were compared in terms of length of hospital stay and occurrence of surgical complications. RESULTS: Histological mandibular invasion occurred in 9 of 35 patients (25.7%). None of the preoperative imaging tests failed to detect bone invasion which resulted in a sensitivity of 100% for both MRI and CT. CT had slightly higher specificity than MRI (61.9% and 57.1% respectively) in predicting bone invasion, but no statistically significant difference was found (P=0.32). Specificity of CT and MRI was higher in the edentulous group (75% and 625% respectively) than in the dentate group (53.8% both), although no statistically significant difference was found. The length of hospital stay was increased in the segmental resection group (25±14.5 days) compared to the marginal resection group (13±4.6 days; P=0.004) and to the hemimandibulectomy group (15±7.2 days; P=0.014). Occurrence of post-operative complications, across all categories, was increased in the segmental resection group (70%, n=7/10; P=0.006) compared to the marginal resection group (8.3%, n=1/12) and to the hemimandibulectomy group (23.1%, n=3/13; P=0.04). CONCLUSION: MRI and CT being equivalent in detecting mandibular invasion, we suggest MRI as single imaging technique in the preoperative assessment of oral cavity SCC. Specificity could be increased if combined with PET/CT, in order to reduce the number of unnecessary mandibular interruptions.

[Hyperlipidemia in patients with inner ear disturbances]. / Hiperlipoproteinemie w zaburzeniach funkcji ucha wewnetrznego.

The aim of this study was to evaluate the occurrence of hyperlipidemia in patients suffering from vertigo, and/or tinnitus and/or hearing loss of unknown origin. 48 patients (25 women and 23 men) were included into this study. All patients had a negative previous medical history of any metabolic, cardiovascular or neurological disorders. Our results were compared to the control group of 31 healthy persons (16 women and 15 men). All subjects had a complete neurootologic examination, appropriate audiometric and vestibular studies. In biochemical evaluation lipid phenotype studies were performed. Hyperlipidemia were classified according to Friedricson criteria. There were some differences in lipid phenotype and severity of hyperlipidemia between this two group.

[Extended resection and radiotherapy for primary intraosseous maxillary carcinoma]. / Carcinome intra-osseux primitif des maxillaires traités par exérèse large et radiothérapie.

INTRODUCTION: Primary intraosseous maxillary carcinoma is a rare squamous cell carcinoma developing from remnants of the odontogenic epithelium. Risk factors are unknown and it may occur at any age. Little epidemiological data is available and few series include a sufficient number of patients. We assessed the prognosis of these tumors after wide exeresis (margin of 2 cm) followed by adjuvant radiotherapy. METHODS: We reviewed the treatment and outcome data in nine cases of primary intraosseous maxillary carcinoma from 1995 to 2010. The WHO diagnostic criteria were used. We analyzed the demographic, clinical, and radiological data, as well as the type of treatment and the outcome of patients. RESULTS: The gender ratio was 3.5/1, and the mean age 40.2 years. The most frequent presentation was a unilocular osteolytic lesion with an irregular contour, between 24 and 60 mm, in the mandibular angle. Extended tumor resection was performed in all patients. Reconstruction was performed with a fibula flap in seven patients. Five patients underwent adjuvant radiotherapy. The survival rate at 2 years was 100%. The mean follow-up was 6.9 years (2-14 years) at the end of the study. Two patients were treated for a relapse and one died after 3 years of follow-up. DISCUSSION: The combined treatment was efficient on primary intraosseous maxillary carcinoma. The diagnosis is made with strict clinical, radiological, and histological criteria. The intraosseous location of these tumors requires an early diagnosis and aggressive treatment combining broad exeresis followed by adjuvant radiotherapy to avoid recurrence and have an optimal survival rate.