Eleftherios Vairaktaris

Panoramic radiograph, computed tomography or magnetic resonance imaging. Which imaging technique should be preferred in bisphosphonate-associated osteonecrosis of the jaw? A prospective clinical study

It was the aim of the present study to find out which radiological imaging techniques allow assessing the extent of bisphosphonate-associated osteonecrosis of the jaw (BONJ) in an adequate way. Twenty-four patients suffering from BONJ were included in the study. Before surgery, each patient was examined with panoramic radiograph, contrast-enhanced magnetic resonance imaging (MRI) and non-enhanced computed tomography. The detectability of BONJ was assessed for the three imaging techniques. The extent of the jaw region affected by BONJ was determined in MRI and CT scans and compared to the intra-operative situation. The detectability of BONJ lesions was 54% for panoramic radiographs, 92% for MRI scans and 96% for computed tomography (CT) scans. The intra-operatively assessed extent of BONJ correlated significantly with the measurements on CT scans (p = 0.0004) but did not correlate significantly with the measurements in MRI scans (p = 0.241). The intra-operatively measured extent of BONJ differed significantly from the CT measurements (p = 0.00003) but not from the MRI data (p = 0.137). Although MRI as well as CT have a high detectability for BONJ lesions that exceeds that of panoramic radiographs by far, both techniques show problems with the exact assessment of the extent of BONJ lesions in the individual patients. Therefore, the relevance of MRI and CT for the preoperative assessment of the extent of BONJ lesions is limited. Future research should focus on the identification of imaging techniques that allow assessing the extent of BONJ lesions with a higher accuracy.

Methylenetetrahydrofolate reductase polymorphism and minor increase of risk for oral cancer

Purpose: We investigated whether the mutant methylenetetrahydrofolate reductase (MTHFR) increases risk for oral cancer. The common germ-line mutation C677T in the MTHFR gene significantly diminishes specific activity of the enzyme, which is responsible for the circulating form of folate. Folate deficiency is associated with increased risk for thrombosis, as well as for several types of cancer, through disruption of DNA methylation, DNA synthesis and deficient DNA repair. Methods: We searched for the C677T mutation by restriction fragment analysis of PCR products in DNA samples of 110 patients with oral squamous cell carcinoma and 120 healthy controls of comparable ethnicity, age and sex. Results: The number of heterozygotes was significantly different in the two groups (P<0.005), as well as in subgroups of patients with or without a positive family history for cancer, compared to normal controls (P<0.01 and P<0.005, respectively). Furthermore, the subgroup of patients with a positive family history for thrombophilia had a significant increase both in the frequencies of mutant alleles (P<0.01) and heterozygotes (P<0.001) in comparison to normal controls. Conclusions: The obtained results suggest that the MTHFR mutation is a minor contributing factor in oncogenesis in the oral region, in conjunction with low dietary uptake of folate.

Phosphorylation of Akt (Ser473) Predicts Poor Clinical Outcome in Oropharyngeal Squamous Cell Cancer

Background: Several lines of laboratory evidence support a role of persistent activation of Akt pathway in oropharyngeal squamous cell carcinoma (OSCC) progression. Loss of phosphatase PTEN is one of the proposed mechanisms of Akt activation. We sought to determine the prognostic significance of Akt activation in a cohort of patients with OSCC as well as the association between phosphorylated (activated) Akt and PTEN levels. Methods: Using a novel system of in situ quantitative protein expression analysis (AQUA), we studied the protein expression levels of phosphorylated Akt (p-Akt) and PTEN on a tissue microarray. The array included 79 OSCCs with a mean follow-up of 36 months. Results: Patients with tumors expressing low tumor p-Akt levels had lower 5-year local recurrence rates (5% versus 38%). Additionally, these patients had improved 5-year overall survival rates (45% versus 27%). This survival effect was likely due to disease recurrence, as there was no difference in death without recurrence between low- and high-expressing groups. In adjusted analysis, tumor p-Akt expression was a strong predictor of local recurrence. A significant inverse relationship was found between nuclear p-Akt and nuclear PTEN: Tumors with high nuclear p-Akt had low nuclear PTEN and vice versa. Conclusions: Akt activation in OSCC is associated with adverse patient outcome, indicating that Akt is a promising molecular target in OSCC. PTEN loss may be one of the mechanisms of Akt activation in OSCC. (Cancer Epidemiol Biomarkers Prev 2007;16(3):553–8)

Three-dimensional Analysis of Facial Symmetry in Cleft Lip and Palate Patients Using Optical Surface Data

Aim:Presentation of a new technique to determine the plane of symmetry of a face, and to assess the degree of facial symmetry in patients with unilateral cleft lip and palate based on three-dimensional (3D) optical surface data.Patients and Methods:After having determined a plane of symmetry according to optical 3D facial surface data, we identified differences in landmarks, the surface areas of the upper lip vermilion and nostrils and virtual volumes of the midface, nose and upper lip for cleft and unaffected sides in forty 10-year-old patients suffering from complete unilateral cleft lip, alveolus and palate. The children had undergone lip repair via the Tennison-Randall technique and had received subsequent orthodontic treatment (but not secondary osteoplasty).Results:Statistically significant differences were apparent between cleft and non-cleft sides in terms of the nasal landmarks, nostril angle and virtual volume of the nose. The upper lip was symmetrical when cleft and non-cleft sides were compared.Conclusions:This new technique of symmetry analysis reveals that the noses of 10-year-old patients with complete unilateral cleft lip and palate who had not undergone revisional surgery present a measurable and significant degree of asymmetry, while the upper lip is symmetrical as a consequence of interdisciplinary treatment by orthodontists and oral and maxillofacial surgeons. Further 3D analyses on larger numbers of patients will allow more comprehensive and consistent analysis of the potential and limitations of various surgical and conservative methods so as to identify those techniques with the best outcome in terms of facial symmetry.ZusammenfassungZiel:Ziel der Studie war es, eine neue Technik zur Beurteilung der Symmetrieebene des Gesichts auf Basis dreidimensionaler Datensätze vorzustellen und ihre Anwendung bei Patienten mit einseitiger Lippen-Kiefer-Gaumen-Spalte zu demonstrieren.Patienten und Methodik:Bei vierzig 10-jährigen Patienten mit einseitiger, vollständiger Lippen-Kiefer-Gaumen-Spalte, die bisher keine sekundäre Osteoplastik erhalten hatte, aber alle kieferorthopädisch behandelt wurden, erfolgte mit Hilfe von optischen 3-D-Daten der Gesichtsoberfläche und einer spezialisierten Software die Bestimmung der Symmetrieebene. Danach wurden die Unterschiede zwischen Landmarken, Flächen des Lippenrots und der Nasenlöcher sowie virtueller Volumina des Mittelgesichts, der Nase und der Oberlippe getrennt nach Gesichtshälften berechnet.Ergebnisse:Zwischen der Gesichtshälfte mit Spaltbildung und der Seite ohne Spalte bestanden statistisch signifikante Unterschiede in Bezug auf Landmarken, Winkel, Flächen und Volumina der Nasen. Im Bereich der Oberlippe wurden keine statistisch signifikanten Unterschiede zwischen der Spaltseite und der nicht betroffenen Seite bestimmt.Schlussfolgerungen:Die vorgestellte Technik der Symmetrieanalyse zeigt beim vorliegenden Patientengut, dass 10-jährige Patienten mit einseitiger Lippen-Kiefer-Gaumen-Spalte, die keine Korrekturoperationen im Verlauf erhielten, eine messbare, statistisch signifikante Asymmetrie der Nase aufweisen. Die Oberlippe dagegen ist bedingt durch das interdisziplinäre Behandlungskonzept aus kieferorthopädischen und mund-, kiefer- und gesichtschirurgischen Maßnahmen symmetrisch. Weitere dreidimensionale Analysen einer größeren Anzahl von Patienten werden die Möglichkeiten und Grenzen der verschiedenen operativen und konservativen Behandlungsmöglichkeiten herausstellen und die Auswahl des Behandlungskonzeptes erleichtern, das in Bezug auf die Gesichtssymmetrie mit den besten Ergebnissen aufwartet.

Effects of bioactive glass and beta-TCP containing three-dimensional laser sintered polyetheretherketone composites on osteoblasts in vitro

Because of their excellent physical properties nonresorbable thermoplastic polymers have become more important for the field of reconstructive surgery. Aim of the present study was to investigate the effects of laser sintered polyetheretherketone (PEEK) with incorporated osteoconductive and bioactive bone substitution materials on osteoblasts in vitro. Human osteoblasts (hFOB 1.19) were seeded onto laser sintered PEEK samples containing nano-sized carbon black, beta-tricalciumphosphate (beta-TCP), and bioactive glass 45S5. Osteoblasts were investigated for cell viability, cell proliferation and cell morphology. A constant proliferation of osteoblasts could be observed on all samples with the highest values for bioactive glass containing samples at day 7 (OD 1.76 +/- 0.22) and day 14 (OD 3.75 +/- 0.31) and lowest values for beta-TCP containing probes throughout the study compared with the PEEK pure control group. Highest cell viability was observed for Bioglass containing probes (95.5 +/- 3.32)% whereas osteoblasts seeded on beta-TCP containing probes showed reduced viability (84.4 +/- 4.32)%. Laser sintered PEEK implants seem to be attractive candidates for use as bone substitutes for reconstructive surgery because of their biocompatibility, individual shape, and the possibility of compounding bioinert polymer powder with osteoconductive and bioactive materials which might benefit bone formation in vivo.

Gene polymorphisms related to angiogenesis, inflammation and thrombosis that influence risk for oral cancer

Genetic association studies have implicated functional DNA polymorphisms in genes encoding factors related to angiogenesis, inflammation and thrombosis with increased risk for oral squamous cell carcinoma (OSCC). This study examines possible interactions between nine such genotype polymorphisms and their combinatory effect in assessing the OSCC risk in a European population. OSCC cases (N=162) and healthy controls (N=168) of comparable age, gender, and ethnicity (Greeks and Germans) were studied. Multivariate logistic regression models were constructed in order to assess the contribution of homozygous or heterozygous variant genotypes of polymorphisms MMP-1 (-1607 1G/2G), MMP-3 (-1171 5A/6A), MMP-9 (-1562C/T), TIMP-2 (-418C/G), VEGF (+936C/T), GPI-alpha (+807C/T), PAI-1 (4G/5G), ACE (intron 16D/I) and TAFI (+325C/T) upon overall, early and advanced stages of OSCC. Four out of nine polymorphisms affecting PAI-1, MMP-9, TIMP-2 and ACE expression contributed significantly in OSCC prediction in the various logistic regression models. Based on these findings and previous reports, possible interactions of the implicated factors leading to OSCC development, as well as an algorithm of risk estimation are discussed.

Orbital cellulitis, orbital subperiosteal and intraorbital abscess. Report of three cases and review of the literature

INTRODUCTION Orbital cellulitis is usually a complication of paranasal sinus infection. Either the infection may dissect under the periosteum and lead to subperiosteal abscess (SPA) or intraorbital abscess may be formed secondary to a progressive and localized cellulitis. Without appropriate treatment orbital infection may lead to serious complications, even death. REPORT OF CASES Three cases are described, one of orbital cellulitis, one of SPA and one of intraorbital abscess and the literature is being reviewed. CONCLUSION Prompt treatment is mandatory to avoid visual loss or intracranial complications. Initially, IV antibiotics may be administered, but if no improvement appears within 48h, surgical drainage of the orbit and the affected sinuses must be performed. In medial or medial-inferior SPA a transnasal approach is used, but in superior orbital abscess an external incision is required.

Genetic association of cytokine DNA polymorphisms with head and neck cancer

Mutations in oncogenes or tumor suppressor genes, as well as environmental factors such as tobacco chewing or smoking, poor oral hygiene, ill-fitting dental appliances, infection by certain HPV types, or alcohol abuse, seem to be involved in the multifactorial process of carcinogenesis in head and neck. Recently, several genetic association studies have indicated that common DNA polymorphisms in low penetrance genes may affect the susceptibility of an individual to malignancy. Cytokines are an important group of proteins that regulate and mediate inflammation and angiogenesis. Tumor growth, invasion and metastasis are facilitated when there is a deregulation in their production. Cytokines include interleukins (ILs), tumor necrosis factors (TNFs) and certain growth factors (GFs). A number of genetic association studies have recently investigated the putative correlation between functional DNA polymorphisms in cytokine genes and head and neck carcinomas. This review discusses the findings of such studies in oral, nasopharyngeal and esophageal squamous cell carcinomas. Extensive research has indicated that functional polymorphisms affecting gene expression of IL-4,-6,-8,-10 as well as TNF-alpha are strongly associated with increased risk for oral cancer. Gene expression of TNF-alpha seems to be associated also with esophageal carcinomas, while for nasopharyngeal cancer the picture is yet unclear. It is generally believed that such genetic association studies will gradually increase our knowledge regarding the predisposed manifestation and advancement of these malignancies in the head and neck region.

Determination of facial symmetry in unilateral cleft lip and palate patients from three-dimensional data: technical report and assessment of measurement errors.

Objective To assess measurement errors of a novel technique for the three-dimensional determination of the degree of facial symmetry in patients suffering from unilateral cleft lip and palate malformations. Design Technical report, reliability study. Setting Cleft Lip and Palate Center of the University of Erlangen-Nuremberg, Erlangen, Germany. Patients The three-dimensional facial surface data of five 10-year-old unilateral cleft lip and palate patients were subjected to the analysis. Distances, angles, surface areas, and volumes were assessed twice. Main Outcome Measures Calculations were made for method error, intraclass correlation coefficient, and repeatability of the measurements of distances, angles, surface areas, and volumes. Results The method errors were less than 1 mm for distances and less than 1.5° for angles. The intraclass correlation coefficients showed values greater than .90 for all parameters. The repeatability values were comparable for cleft and noncleft sides. Conclusion The small method errors, high intraclass correlation coefficients, and comparable repeatability values for cleft and noncleft sides reveal that the new technique is appropriate for clinical use.

miR-186, miR-3651 and miR-494: Potential biomarkers for oral squamous cell carcinoma extracted from whole blood

microRNAs (miRNAs) are aberrantly expressed in the whole blood of patients suffering from different types of cancer. Collection of whole blood samples is a minimally invasive procedure. To date, little is known concerning the altered miRNA expression in patients suffering from oral squamous cell carcinoma (OSCC). The present study aimed to evaluate the difference in miRNA expression in whole blood samples in OSCC patients as compared to healthy volunteers who served as controls. In 20 blood samples from patients and healthy volunteers, the expression patterns of 1,205 human miRNAs were examined by miRNA microarray in order to identify those with the most pronounced differential expression. The results were verified by quantitative RT-PCR (RT-qPCR) for miR-186, miR-3651 and miR-494 using 57 samples of patients and 33 samples of healthy volunteers. Receiver operating characteristic (ROC) curves and the highest Youden index were calculated in order to assess cut-off points (COPs) that allowed the distinguishing of blood samples of OSCC patients from those of healthy volunteers. Significantly different expression rates were found for miR-186 (p=0.01), miR-3651 (p=0.0001) and miR-494 (p=0.004) between the OSCC patients and healthy controls. In the OSCC patients, there was a 2-fold upregulation for miR-494 and miR-3651 and a 2-fold downregulation for miR-186. Based on the determined COPs, significant correlations between miR-3651 overexpression and lymph node status (p=0.04), tumor grade (p=0.02) and clinical stage (p=0.04) were indicated. Aberrant expression levels of miR-186, miR-494 and miR-3651 in whole blood samples of OSCC patients may provide the possibility to establish a minimally invasive screening method for OSCC.