Thomas Fillies

HIF1-alpha overexpression indicates a good prognosis in early stage squamous cell carcinomas of the oral floor

BackgroundHypoxia-inducible factor 1 (HIF-1) is a transcription factor, which plays a central role in biologic processes under hypoxic conditions, especially concerning tumour angiogenesis. HIF-1α is the relevant, oxygen-dependent subunit and its overexpression has been associated with a poor prognosis in a variety of malignant tumours. Therefore, HIF-1α expression in early stage oral carcinomas was evaluated in relation to established clinico-pathological features in order to determine its value as a prognostic marker.Methods85 patients with histologically proven surgically treated T1/2 squamous cell carcinoma (SCC) of the oral floor were eligible for the study. Tumor specimens were investigated by means of tissue micro arrays (TMAs) and immunohistochemistry for the expression of HIF-1. Correlations between clinical features and the expression of HIF-1 were evaluated by Kaplan-Meier curves, log-rank tests and multivariate Cox regression analysis.ResultsHIF-1α was frequently overexpressed in a probably non-hypoxia related fashion. The expression of HIF-1α was related with a significantly improved 5-year survival rate (p < 0.01) and a significantly increased disease free period (p = 0.01) independent from nodal status and tumour size. In primary node negative T1/T2 SCC of the oral floor, absence of HIF-1α expression specified a subgroup of high-risk patients (p < 0.05).ConclusionHIF-1α overexpression is an indicator of favourable prognosis in T1 and T2 SCC of the oral floor. Node negative patients lacking HIF-1α expression may therefore be considered for adjuvant radiotherapy.

Cytokeratin 8/18 expression indicates a poor prognosis in squamous cell carcinomas of the oral cavity

BackgroundIntermediary filaments are involved in cell motility and cancer progression. In a variety of organs, the expression of distinct intermediary filaments are associated with patient prognosis. In this study, we seeked to define the prognostic potential of cytokeratin and vimentin expression patterns in squamous cell carcinomas (SCCs) of the oral cavity.Methods308 patients with histologically proven and surgically treated squamous cell carcinomas of the oral cavity were investigated for the immunohistochemical expression of a variety of intermediary filaments including high- and low-molecular weight cytokeratins (Cks), such as Ck 5/6, Ck 8/18, Ck 1, CK 10, Ck 14, Ck 19 and vimentin, using the tissue microarray technique. Correlations between clinical features and the expression of Cytokeratins and vimentin were evaluated statistically by Kaplan-Meier curves and multivariate Cox regression analysis.ResultsThe expression of Ck 8/18 and Ck 19 were overall significantly correlated with a poor clinical prognosis (Ck 8/18 p = 0.04; Ck19 p < 0.01). These findings could also be reproduced for Ck 8/18 in primary nodal-negative SCCs and held true in multivariate-analysis. No significant correlation with patient prognosis could be found for the expression of the other cytokeratins and for vimentin.ConclusionThe expression of Ck 8/18 in SCCs of the oral cavity is an independent prognostic marker and indicates a decreased overall and progression free survival. These results provide an extended knowledge about the role of intermediary filament expression patterns in SCCs.

Evaluation of accuracy of insertion of dental implants and prosthetic treatment by computer-aided navigation in minipigs.

The survival of loaded implants is critically dependent on their biomechanical stability. We have used a computer-guided navigation technique to evaluate the accuracy of computer-assisted insertion for immediately-loaded implants in minipigs. On the basis of computed tomographical data, the Robodent system was used for preoperative planning and guidance of inserting the implant. An optical tracking system allowed positioning of the implant and immediate prosthetic rehabilitation by inserting it in a plaster model and during the operation. Postoperative computed tomograms (CT) showed that the implants were placed precisely in the preoperatively planned position. The accuracy achieved corresponded well with the spatial resolution of the CT used. Immediate placement of the prefabricated crowns resulted in favourable occlusal positioning. Histological cross-sections showed that the implants were biomechanically stable. The accuracy of insertion of oral implants illustrated here suggests that insertion and prosthetic modelling of implants may benefit from computer-assisted navigation.

Perioperative complications in infant cleft repair

BackgroundCleft surgery in infants includes special risks due to the kind of the malformation. These risks can be attributed in part to the age and the weight of the patient. Whereas a lot of studies investigated the long-term facial outcome of cleft surgery depending on the age at operation, less is known about the complications arising during a cleft surgery in early infancy.MethodsWe investigated the incidence and severity of perioperative complications in 174 infants undergoing primary cleft surgery. The severity and the complications were recorded during the intraoperative and the early postoperative period according to the classification by Cohen.ResultsOur study revealed that minor complications occurred in 50 patients. Severe complications were observed during 13 operations. There was no fatal complication in the perioperative period. The risk of complications was found to be directly correlated to the body weight at the time of the surgery. Most of the problems appeared intraoperatively, but they were also followed by complications immediately after the extubation.ConclusionIn conclusion, cleft surgery in infancy is accompanied by frequent and sometimes severe perioperative complications that may be attributed to this special surgical field.

Vascular basis of mucosal color

BackgroundBesides the color of the teeth the color of the alveolar gingiva plays a crucial role in esthetic rehabilitation in dento-alveolar treatment. Whereas nowadays the color of the teeth can be determined exactly and individually, the specific influence of the red color of the gingiva on treatment has not been assessed yet. The aim of this study was to evaluate the vascularization as the basis for gingival esthetics.MethodsStandardized photographs of defined areas of the alveolar gingiva in operated and non-operated patients were taken and assigned to groups with same characteristics after color comparisons. In addition, histologic and immunohistologic analyses of gingival specimens were performed for qualitative and quantitative assessment of vessels and vascularization. Finally, colors and number of vessels were correlated.ResultsOur results demonstrated three different constellations of colors of the alveolar gingiva in healthy patients. The operated patients could not be grouped because of disparate depiction. There was a clear correlation between color and vessel number in the alveolar gingiva.ConclusionOur investigations revealed the connections between vascularization and gingival color. Recommendations for specific change or even selection of colors based on the results cannot be given, but the importance of vascularly based incision lines was demonstrated.

Image-based biomimetric approach to design and fabrication of tissue engineered bone

Abstract The utilization of computer-aided technologies in tissue engineering has evolved in the development of a new field of computer-aided tissue engineering (CATE). Computer technologies can be used for the design and manufacturing (CAD/CAM) of scaffolds prepared from a specific building material to form a defined three-dimensional tissue. The hypothesis of the present experimental study was that autogenous cultivated osteoblasts can be grown on individualised scaffolds to improve bone regeneration in mandibular defects. Autogenous bone cells of minipigs were harvested and multiplicated in culture. Mandibular defects were created in the body and temporomandibular joint (TMJ) region of the mandible and a CT scan performed. The scaffold of the defect site was modelled by computed tomography (CT)-based rapid prototyping of polylactite/polyglycosite copolymers. Cells were seeded on the mandibular body scaffolds and the defects were reconstructed by the artificial materials. CT scans were performed directly after insertion and animals were sacrificed after 3 and 30days of healing time. The intraoperative situation as well as the postoperative CT scans demonstrated an accurate anatomical modelling of the defect sites. Transplanted cell/scaffold constructs appeared to enhance bone formation in the defect site as revealed by histological analysis. The combination of computer technology and tissue engineering may improve bone reconstruction approaches in the future.

Cytokeratin and protein expression patterns in squamous cell carcinoma of the oral cavity provide evidence for two distinct pathogenetic pathways

Squamous cell carcinoma (SCC) of the oral cavity is a morphological heterogeneous disease. Various cytokeratin (CK) expression patterns with different prognostic values have been described, but little is known concerning the underlying biological cell mechanisms. Therefore, the present study investigated 193 cases of oral SCCs using immunohistochemistry for α/β/γ-catenin, glucose transporter 1, caspase-3, X-linked inhibitor of apoptosis protein, hypoxia inducible factor-1α, carbonic anhydrase 9, heat shock protein (hsp) 70, mast/stem cell growth factor receptor, p21, p27, p16, p53, B-cell lymphoma 6, epidermal growth factor receptor, cyclin D1 and CK1, 5/6, 8/18, 10, 14 and 19. Expression patterns were analyzed with biomathematical permutation analysis. The present results revealed a significant association between the expression of low-molecular weight CK8/18 and 19 and a high-tumor grade, β and γ-catenin expression, deregulated cell cycle proteins and a predominant localization of the tumor on the floor of the mouth. By contrast, expression of high-molecular weight CK1, 5/6, 10 and 14 was significantly associated with the expression of p21 and hsp70. In conclusion, the current study presents evidence for the existence of two parallel pathogenetic pathways in oral SCCs, characterized by the expression of low- and high-molecular weight CKs. Additional studies are required to demonstrate the extent that these results may be used to improve therapeutic regimens.

Site-specific gene expression patterns in oral cancer

BackgroundSquamous cell carcinomas (SCCs) are the most prevalent malignant tumours within the head and neck. Evidence exists that distinct genes are differentially regulated in SCCs of the oral cavity compared to other head and neck regions. Given this background, the aim of this study was to investigate whether such tumour site-specific gene expression can also be observed in different localizations within the oral cavity.MethodsUsing tissue microarrays (TMAs), we investigated 76 SCCs of the floor of the mouth, 49 SCCs of the tongue and 68 SCCs of other anatomic regions within the oral cavity. The expression of 17 genes involved in cell cycle and growth control (p16, p21, p27, p53, cyclin D1, EGFR, c-kit, bcl-6), cell adhesion (alpha-, beta-, and gamma-catenin), and apoptosis/stress response genes (Hif-1-alpha, Glut 1, CA IX, caspase, hsp70, XIAP) were investigated by means of immunohistochemistry. The data were subjected to chi2, interdependency and Kaplan-Meier analysis.ResultsOur study suggests a remote difference in the site-specific gene expression patterns of oral cancer. X-linked inhibitor of apoptosis (XIAP) showed a significantly higher expression (p <0.05) in SCCs of the floor of the mouth compared to SCCs of the tongue and other locations within the oral cavity. The increased XIAP expression was further associated with significantly decreased overall survival in all cases of SCCs of the oral cavity (p <0.05). Expression levels of p53, CA IX, beta-catenin, Hif-1-alpha, and c-kit were also observed to be inversely related between SCCs of the floor of the mouth and those of the tongue respectively, although these differences did not reach statistical significance. Overall and event-free survival did not differ in patients with T1/T2/N0 SCCs according to tumour localization.ConclusionIn summary, the protein expression patterns of SCCs of the oral cavity suggest the existence of a molecular and morphological spectrum of SCCs in the oral cavity. In particular the expression pattern of XIAP indicates distinct gene expression patterns between carcinomas of the floor of the mouth and oral tongue cancer. Further studies are needed to identify possible tumour site-specific factors that influence patient prognosis and management.

Computer based approach for design and treatment of immediately loaded implants

The survival of implants provide superior stability from a clinical point of view when the implant and bone characteristics match the biological and biomechanical requirements of implants. The design and the placement of implants are important factors governing the long term success. We therefore developed on the basis of finite element calculations a new dental implant system indicated for an immediate loading protocol. To optimise loading and to ease the clinical performance of implant treatment image guided navigation was used to insert implants. Implants were inserted in the mandible of minipigs by the robodent system (Straumann, Germany) according to the boundary conditions used in our FEM analysis. Our results indicate that a good accuracy of implant insertion can be achieved. Immediate placement of prefabricated crowns demonstrated a good occlusal relationship. The maximum deviation between the planned and the realised implant position was 0.6mm. Histological analysis demonstrated a biomechanically stable position of implants. We conclude that the design as well as the insertion and prosthetic treatment of oral implants is improved by computer assisted surgery.