Prospective assessment of complications associated with ultrasound activated resorbable pin osteosynthesis in pediatric craniofacial surgery: preliminary results.

Ultrasound activated resorbable pin osteosynthesis (UARPO) has recently shown favourable results in operations on children suffering for craniosynostosis. However, data on complications coming with this new technique in children suffering from craniosynostoses are scarce and have only been assessed retrospectively so far. It has been the aim of the present study to prospectively follow up children undergoing craniosynostosis surgery with a focus on complications related to UARPO materials. Ten pediatric patients (3 female/7 male) were operated due to craniosynostosis at an average age of 9.1±3.8 months using UARPO (SonicWeld/Resorb-X, KLS Martin, Tuttlingen, Germany). Clinical followup evaluations were carried out 1, 3, 6, 9, 12 and 18 months after surgery according to signs of local infection, stability of the remodeled cranial vault and the palpability of the osteosynthesis material. If secondary surgery was necessary, the indication was documented and evaluated by histological and wound smear examinations. No intra-operative or postoperative complications during the inpatient period occurred. 3 patients needed secondary operation due to a localized chronic swelling at the former incision site which developed 3, 9 and 12 months after the operation. Histological examinations yielded a giant cell formation surrounding the resorbable materials in all cases. Additionally, the wound smear showed a bacterial infection in one site. The current prospective study is the first in the field. It reveals a high percentage of delayed foreign body reactions with UARPO, bearing the need of secondary surgery. It seems that this high complication rate found in the present prospective study may weigh out the advantages of UARPO.

Expression of cytokeratin 17 mRNA in oral squamous cell carcinoma cells obtained by brush biopsy: preliminary results.

BACKGROUND: The aim of this study was to determine the detection of cytokeratin (CK) mRNA in oral squamous cell carcinoma (OSCC) cells and to evaluate the CK relevance for OSCC diagnosis in a brush biopsy test. METHODS: Fifty-two pairs of OSCC cells and normal oral mucosal cells were obtained by brush biopsy from OSCC patients. mRNA was extracted from cell pellets for real-time quantitative reverse transcriptase polymerase chain reaction (RT-qPCR). The over-expression levels of CK 17, CK 19 and CK 20 mRNA in OSCC cells were examined by SYBR green real-time RT-qPCR. RESULTS: Compared to normal mucosal cells, the over-expression of CK 17 mRNA was detectable in 40 OSCC cells (76.9%), that of CK 19 mRNA in 19 (36.5%), while that of CK 20 mRNA was not detectable. Compared with CK 19, the mean value of CK 17 mRNA expression level was significantly higher in all 52 patients (P < 0.02). Moreover, the value of CK 17 was significantly higher in T1 and T2 OSCC patients (P < 0.03, respectively), in patients without metastases of neck lymph nodes (P < 0.04), in stage I and stage II patients (P < 0.03 and P < 0.05, respectively) and in well differentiated OSCC patients (P < 0.05). CONCLUSION: Brush biopsy properly serves for detection of CK mRNA using real-time RT-qPCR. This preliminary study demonstrates the CK 17 possibility for application; however, pivotal studies are encouraged to confirm CK 17 as a diagnostic marker of OSCC in a brush biopsy test.

Mandibular bone density and calcium content affected by long-term anticonvulsant treatment in rats.

OBJECTIVE: Bone is perpetually absorbed and reformed, serving also to electrolyte homeostasis, mainly for calcium and phosphorus. Anticonvulsant medications are traditionally considered harmful to bone because of their interaction with the metabolism of vitamin D, due to hepatic enzyme induction. A study of the effect of anticonvulsant medications on mandibular bone quality was undertaken. MATERIALS AND METHODS: 24 Wistar rats in three groups received diphenylhydantoin or diazepam or placebo intraperitoneally (i.p.). Absolute bone weight, bone to body weight ratio, specific bone weight, absolute calcium concentration, calcium to mandibular bone weight ratio and mineral element concentration were examined after animal sacrifice, three months later. From the results it may be concluded that diazepam and diphenylhydantoin administration affect the mandibular bone density and calcium content in terms of absolute weight and specific weight. Mandibular calcium concentration was affected only by diphenhylhydantoin treatment.

The hamster model of sequential oral oncogenesis.

Oral squamous cell carcinoma (OSCC) is a common cancer characterised by low survival rate and poor prognosis. The multistep process of oral carcinogenesis is affected by multiple genetic events such as alterations of oncogenes and tumour suppressor genes. The use of appropriate experimental animal models that accurately represent the cellular and molecular changes which are associated with the initiation and progression of human oral cancer is of crucial importance. The Syrian golden hamster cheek pouch oral carcinogenesis model is the best known animal system that closely correlates events involved in the development of premalignant and malignant human oral cancers. Therefore, we established an experimental system of chemically induced oral carcinogenesis in hamsters, in order to study different stages of tumour formation: normal mucosa, hyperkeratosis, hyperplasia, dysplasia, early invasion, well differentiated OSCC and moderately differentiated OSCC. We investigated the expression of oncogenes EGFR, erbB2, erbB3, FGFR-2, FGFR-3, c-myc, N-ras, ets-1, H-ras, c-fos and c-jun, apoptosis markers Bax and Bcl-2, tumour suppressor genes p53 and p16, and cell proliferation marker Ki-67 in the sequential stages of hamster oral oncogenesis. Here, we describe the findings of the experimental model in regard to the involvement of signal transduction pathways in every stage of cancer development. Increased apoptosis and cell proliferation were observed in early stages of oral oncogenesis. Furthermore, the increased expression of transmembrane receptors (EGFR, erbB2, FGFR-2 and FGFR-3) as well as the increased expression of nuclear transcriptional factors in early stages of oral cancer indicates that these molecules may be used as early prognostic factors for the progression of OSCC. Since the expression of both H-ras and N-ras do not seem to affect signal transduction during oral oncogenesis, it can be assumed that a different signalling pathway, such as the PI3K and/or PLCgamma pathway, may be implicated in the pathogenesis of OSCC.

Diabetes enhances cell proliferation but not Bax/Bcl-2-mediated apoptosis during oral oncogenesis.

Markers of cell proliferation (Ki-67 antigen) and apoptosis (Bax, Bcl-2) were studied in an experimental model of chemically induced carcinogenesis in normal and diabetic (type I) Sprague-Dawley rats. Thirteen diabetic and 12 normal rats developed cancer after 4-nitroquinoline-N-oxide treatment, while 6 diabetic and 6 normal animals were used as controls. The biopsies were classified pathologically (from oral mucosal dysplasia to moderately differentiated squamous cell carcinoma) and studied immunohistochemically using monoclonal antibodies against Bax, Bcl-2 and Ki-67 proteins. The Bcl-2/Bax ratio was almost stable during the oncogenesis process in the diabetic rats, whereas the normal rats showed an increased Bcl-2/Bax ratio during the stage of moderately differentiated carcinoma. In contrast, Ki-67 expression was higher in diabetic rats than in normal ones in almost all stages of oral oncogenesis, and it reached significantly increased levels in the stages of normal control tissue, dysplasia and moderately differentiated squamous cell carcinoma. These data suggest that diabetes results in increased cell proliferation during oral oncogenesis, but this is accomplished without affecting the Bax/Bcl-2-mediated apoptotic pathways.

[Enophthalmos correction in complex orbital floor reconstruction : computer-assisted, intraoperative, non-contact, optical 3D support]. / Enophthalmuskorrektur bei komplexer Orbitarekonstruktion : Computerassistierte, intraoperative, berührungsfreie, optische 3D-Unterstützung.

In the case of displacement of the globe such as enophthalmos induced by trauma, the patient is affected on both counts: function and aesthetics. To prevent double vision or conspicuous asymmetry, exact correction of the globe position is required. The aim of this case report is to demonstrate an intraoperative computer-assisted, non-contact, optical 3D procedure for identification of the globe position to aid in placing the eyeball in the position required in complex reconstruction of the orbital floor. A 33-year-old man presented with a sunken eye on the right side in the horizontal and vertical plane 6 months after having undergone surgery elsewhere for a zygomatico-orbital fracture, also including the orbital floor. The patient was affected by double vision and a noticeable defective globe position. In planning the correction of the globe position, a three-dimensional image of the face with opened eyes was made with the optical sensor. Automatic comparison of symmetry revealed enophthalmos of 4 mm on relative en- and exophthalmometry. The decision was made to lift the orbital floor with a split calvarial bone graft. During surgery the position of the globe was also controlled by the three-dimensional optical technique. At the end of surgery there was exophthalmos of 1 mm. Six weeks after surgery the patient was not affected by any double vision. After 3 and 24 months enophthalmos was 1 mm. This case demonstrates how the non-ionizing, non-contact, optical 3D technique can help in planning, intraoperative transformation, and clinical monitoring to identify the correct position of the corneal vertex in complex orbital floor reconstruction.

[Computer-assisted orbital floor reconstruction. Use of a CAD/CAM implant with intraoperative contact-free 3D endo- and exophthalmometry]. / Computerassistierte Enophthalmuskorrektur. Nutzung eines CAD/CAM-Implantats unter intraoperativer, berührungsfreier 3D-en- und exophthalmometrischer Kontrolle.

Pronounced enophthalmos can restrict patients both functionally and aesthetically. Typical symptoms are double vision on both eyes and obvious asymmetry, both of which were present in the 67-year-old male patient presented in this paper. The resulting data of computed tomography was used to fabricate a patient specific ceramic implant for reconstruction of the left orbital floor with an enophthalmos of 4mm. During the surgery the implant fitted anatomically correct, but exophthalmos occurred. The implant needed to be regraded and recontoured in the dorsal fraction, so that overcorrection could be reduced. With the assistance of optical 3D en- and exophthalmometry during surgery, the position of the cornea vertex was reproducible measured. At the end of surgery, exophthalmos was 1.5 mm. After 12 months, enophthalmos of only 1mm exists. This case displays the combination of a patient specific fabricated implant for reconstruction of the orbital floor with optical 3D-en-and exophthalmometry to correct enophthalmos with a high degree of accuracy. Therefore these two techniques in combination should be used when complex corrections of enophthalmos are needed.

The low VEGF production allele of the +936C/T polymorphism is strongly associated with increased risk for oral cancer.

PURPOSE: Based on the well-established role of vascular endothelial growth factor (VEGF) in tumor-associated angiogenesis in several cancer types and its undefined role in oral oncogenesis, we investigated the possible association of an expression-regulating polymorphism (+936C/T) with risk for oral squamous cell carcinoma (OSCC). METHODS: We studied the allele frequencies of the +936C/T polymorphism in DNA samples of 144 patients with OSCC and 153 healthy controls matched by age, gender and ethnicity, using restriction fragment length polymorphism typing analysis. RESULTS: The low-expression T allele was significantly increased in the total patient group compared to controls (P = 0.008), due to a significant over-representation of C/T heterozygotes compared to C/C homozygotes (P = 0.007). The same pattern was observed in most patient subgroups and more noticeably in patients with a positive family history of cancer (P = 0.001). Interestingly, the increase in T allele frequency was only significant in patients at cancer stages I and II (P = 0.006). CONCLUSIONS: This study clearly indicates that the low-VEGF-production T allele is strongly associated with increased risk for OSCC. In addition, the impressive T allele frequency increment in patients with a positive family cancer history suggests that this allele may also be involved in other malignancies. The fact that this significant increase was observed only in patients with early cancer stages may imply that low VEGF levels might hinder subsequent tumorigenesis. Our findings might be the result of either unidentified properties of the +936 C/T polymorphism or of a strong linkage disequilibrium between this polymorphism and another genetic locus.

The interleukin-8 (-251A/T) polymorphism is associated with increased risk for oral squamous cell carcinoma.

AIMS: In light of recently found contribution of angiogenic and inflammation-related factors to malignancies, this study investigated the possible association of interleukin-8 gene (IL-8) to increased risk of oral cancer. METHODS: The IL-8 (-251 A/T) polymorphism, which influences IL-8 gene expression, was evaluated by restriction fragment length polymorphism analysis in DNA samples of 158 German and Greek patients with oral squamous cell carcinoma and 156 healthy controls of equivalent sex, ethnicity and age. RESULTS: Significant increase of mutant (A-251) allele, which results in higher IL-8 gene expression, was observed in all patients in comparison to normal controls (P<0.001). The A/T heterozygotes had a two-fold greater risk (odds ratio 1.76, CI 1.11-2.79) for developing oral cancer compared to normal TT homozygotes. Furthermore, significantly increased values of mutant allele frequencies compared to controls were observed in all patients as well as in subgroups of patients with or without positive history of cancer (P<0.05 and P<0.001, respectively) and with or without positive history of thrombophilia (P<0.05 and P<0.001, respectively). CONCLUSIONS: In light to known observations of elevated plasma levels of IL-8 in several types of cancer including oral squamous cell carcinoma, the findings of this study suggest that the mutant allele of the (-251 A/T) polymorphism may be a major contributing genetic factor to risk for oral cancer.

Diabetes may increase risk for oral cancer through the insulin receptor substrate-1 and focal adhesion kinase pathway.

In light of recent epidemiological studies that associate diabetes mellitus with increased risk for oral cancer, we investigated in diabetic (type I) and normal rats with induced oral squamous cell carcinoma whether the molecular basis for that putative association involves insulin receptor substrate-1 (IRS-1) and focal adhesion kinase (FAK). Fourteen diabetic and 12 normal rats developed cancer after 4-nitroquinoline-N-oxide treatment, while six diabetic and six normal animals were used as controls. Oral sections were studied using monoclonal antibodies against IRS-1 and FAK proteins. Expression of IRS-1 was significantly higher in diabetic than normal rats, but it decreased in diabetic animals with tumor, especially in more advanced stages. FAK expression was significantly higher in rats with cancer in comparison to the ones without it, regardless the diabetes status. These data suggest that the IRS-1/FAK pathway is altered by diabetes resulting in reduced cell adhesion and possibly increasing risk for oral cancer.

Abundance and localization of skeletal muscle-related erbB2 may stimulate tumour growth during initial stages of oral oncogenesis.

ErbB2 and erbB3 transmembrane receptors, known to be associated with neuronal and skeletal muscle developmental function, seem to play an important role in human oral oncogenesis. This study was designed to determine gradual erbB2 and erbB3 expression in an experimental animal system of induced oral carcinogenesis in Syrian golden hamsters. Thirty-seven animals were divided into one control group (N=7) and three experimental groups (N=10 each one), which were treated with carcinogen 9,10-dimethyl-1,2-benzanthracene and sacrificed at 10, 14 and 19 weeks after treatment. The histological status of observed lesions in the three experimental groups corresponded well with tumour advancement (from oral mucosal dysplasia to moderately differentiated squamous cell carcinoma). Tissue sections ranging from normal mucosa to squamous cell carcinoma were studied using monoclonal antibodies against erbB2 and erbB3 proteins. Cytoplasmic erbB2 expression was gradually increased in pre-cancerous stages, remained stable in initial tumour stages and substantially decreased in moderately-differentiated carcinomas, suggesting that it may be useful as an early prognostic factor. On the contrary, erbB3 was not expressed at all either in normal or tumour tissue.

[Solitary fibrous tumor in the tongue: case report and review of the literature]. / Solitärer fibröser Tumor der Zunge: Fallbericht und Literaturübersicht.

Solitary fibrous tumors (SFT) are rare, mostly fibroblastic tumors usually situated in the pleura. Extrapleural manifestations have been described. However, the oral cavity is an uncommon localisation of this tumor. We report the very unusual case of an SFT affecting the tongue that could be removed completely because of its clear delineation. Intraoperative incisional biopsies were used to exclude malignancy. For definitive classification of the tumor, additional histopathologic examinations had to be carried out. Because SFT exhibit malignant behavior only in exceptional cases and their recurrence after complete removal has never been encountered, surgery can focus on the preservation of undisturbed function of the tongue.

State of the art of fusion of computed tomography data and optical 3D images.

When three-dimensional imaging is necessary in dentistry, oral surgery or maxillofacial surgery, conventional computed tomography or cone beam computed tomography is chosen regularly. However, there are two obvious drawbacks. Metallic restorations lead to pronounced streak artefacts in conventional computed tomography. Moreover, the resolution of both conventional computed tomography and cone beam computed tomography is limited to 0.3 mm. This resolution is not sufficient for the fabrication of dental restorations. In order to improve the quality of the two different computed tomography techniques and to eliminate streak artefacts, fusion with optical 3D images can be considered. The resolution of optical 3D images can reach the range of some microms depending on the calibration of the sensor. Metal artefacts do not occur. The fusion of computed tomography images without artefacts and optical 3D images leads to a mean deviation of corresponding points for the two imaging techniques of 0.1262 +/- 0.0301 mm. When computed tomography images with metal artefacts are used, the deviation increases up to 0.2671 +/- 0.0580 mm. The accuracy of image fusion is significantly reduced by metal artefacts (p < 0.0005). When image fusion of computed tomography and optical 3D images is used in clinical studies, the mean deviation of corresponding points for the two imaging techniques for mandible and maxilla is 0.66 +/- 0.49 mm and 0.56 +/- 0.48 mm, respectively. The available data on image fusion show that the quality of computed tomography data without streak artefacts can be significantly improved by registration with optical 3D images. The precision of the fused images exceeds the resolution of the original computed tomography. When streak artefacts are present, image fusion makes it possible to increase the quality of the data to the level of the original resolution of computed tomography without artefacts.

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.

Association of platelet glycoprotein Ia polymorphism with minor increase of risk for oral cancer.

AIMS: In light to association of increased platelet glycoprotein Ia (GPIa) expression with tumor invasion and metastasis in several types of cancer, we investigated the possible contribution of a common polymorphism (C807/T807), affecting the GPIa gene expression, in the development of oral cancer. METHODS: DNA samples of 110 patients with oral cancer and 114 healthy controls were examined by allele-specific polymerase chain reaction followed by electrophoretic analysis. RESULTS: The mutant T807 allele homozygotes were significantly increased in the group of patients compared to the control group (P < 0.001). Furthermore, significantly increased frequency of mutant alleles compared to controls was observed in the subgroup of patients with a positive history for cancer (P < 0.01). CONCLUSIONS: The obtained results indicate that the C807/T807 polymorphism is indeed a genetic predisposing factor which contributes to increased risk for oral cancer.

Plasminogen activator inhibitor-1 polymorphism is associated with increased risk for oral cancer.

In light of the recently observed contribution of thrombosis-related factors to carcinogenesis, we investigated the possible association of plasminogen activator inhibitor-1 (PAI-1) with increased risk for oral cancer. In DNA samples of 104 patients with oral squamous cell carcinoma and 106 healthy controls of comparable ethnicity, age and sex, we studied the 4G/5G polymorphism in the PAI-1 gene, which affects its expression. The mutant 4G allele and carrier frequencies were significantly increased in patients compared to controls (65.9% versus 49.5%; 88.5% versus 69.8% respectively, P<0.01). That increase was even higher in patients with a positive family history for thrombophilia or without one for cancer (P<0.001). Interestingly, significant difference from controls was observed only in patients with cancer stages I and II. These findings suggest that the 4G allele, by resulting in higher PAI-1 expression, is a major contributing factor in early stages of oral oncogenesis. Possibly, increased PAI-1 promotes initial development of oral cancer through regulation of cell detachment and delays further tumor progression by inhibiting vascularization.

Cell proliferation and apoptosis culminate in early stages of oral oncogenesis.

Markers of cell proliferation (Ki-67 antigen) and apoptosis (Bax, Bcl-2) were studied in an experimental system of induced oral carcinogenesis in Syrian golden hamsters. Thirty-seven animals were divided into one control group and three experimental groups, which were treated with a carcinogen and sacrificed at 10, 14 and 19 weeks after treatment. The histological status of the lesions in the three experimental groups corresponded well with tumour advancement (from oral mucosal dysplasia to moderately differentiated squamous cell carcinoma). Tumour sections were studied using monoclonal antibodies against Bax, Bcl-2 and Ki-67 proteins. Pro-apoptotic Bax expression maintained high levels during all stages of oral carcinogenesis. Anti-apoptotic Bcl-2 expression decreased significantly in dysplastic and early invasion lesions and consequently increased almost to normal tissue level in consequent stages. Finally, Ki-67 expression increased sharply in initial stages of oral carcinogenesis, but significantly decreased in later stages.

Strong association of interleukin-6 -174 G>C promoter polymorphism with increased risk of oral cancer.

In view of the recently found contribution of factors associated with thrombosis and inflammation to carcinogenesis, we investigated the possible association of interleukin-6 (IL-6) with an increased risk of oral cancer. In DNA samples of 162 patients with oral squamous cell carcinoma and 156 healthy controls of comparable ethnicity, age and sex, we studied the -174 G>C polymorphism in the IL-6 gene, which affects its transcription. C allele frequencies were significantly increased in patients compared to controls, 42.6% versus 23.1% (p<0.001). The CC homozygotes had a 7-fold greater risk of developing oral cancer (odds ratio 7.39, 95% CI 2.61-20.92), while the GC heterozygotes had a 4-fold greater risk (odds ratio 3.74, 95% CI 2.29-6.11). A significant increase in C alleles was observed in patients regardless of their smoking or alcohol consumption habits, early or advanced stage of cancer, and presence or absence of a family history for cancer or thrombophilia (p<0.001; Fisher's exact test). These findings suggest that the -174 G>C polymorphism, by affecting IL-6 gene expression, is strongly associated with oral oncogenesis.

Lingual thyroid: a new surgical approach--a case report.

Ectopic lingual thyroid is a rare developmental anomaly, presenting in the adult with obstructive symptoms during respiration, deglutition and speech. The main therapeutic issue after exact diagnosis is the restoration of thyroid function, and surgical intervention, when necessary, has to deal with problems related to the site and function of the ectopic gland. A case of a 25-year-old female with dyspnoea and dysphagia due to a 3 x 4 cm ectopic lingual thyroid, excised by an original peroral approach via a mandibular midline osteotomy, is reported. Our surgical technique is described and the diagnostic and therapeutic problems are reviewed.

Mycobacterial cervical lymphadenitis. A clinicopathological study of 3 cases.

Three adult patients with tuberculous cervical (submandibular) lymphadenitis were treated in the past year in the Department of Oral and Maxillofacial Surgery, Evangelismos Hospital, University of Athens. None had a history of exposure to tuberculosis. In all, the chest X-rays were clear but the PPD tests were positive. All patients underwent excisional biopsy of grossly involved lymph nodes and histological examination and special stains confirmed the diagnosis. The patients were subsequently treated with triple drug administration. Antituberculosis chemotherapy consisted of isoniazid, rifampin and ethambutol and all are well after a follow-up of 9, 10 and 11 months respectively. Medical approaches often failed to diagnose tuberculous cervical lymphadenitis conclusively, and this disease remains a diagnostic and therapeutic challenge, because it mimics other pathological processes. The treatment of choice seems to be surgical excision and long term antituberculosis chemotherapy. Surgery provides a rapid tissue diagnosis, because the histological examination of the excisional biopsy is the most reliable diagnostic test.