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Head and neck cancer is the tenth leading cause of cancer mortality. Ninety percent of tumours in the oral cavity are squamous cell carcinomas. Information about the exact localisation of OSCC is missing in the literature. In the present study, we retrospectively analysed a total of 1501 OSCC patients, who were treated between 1975 and 2009. The purpose of this study was to examine the localisation of OSCC tumours and to analyse the influence of various parameters on tumour localisation. 71.5% of these patients were male and 28.5% were female. The mean age was 60 years. The most common sites of OSCC occurrence were the floor of the mouth and the anterior base of the mouth. The hard palate was the most affected anatomical area of the maxilla. Descriptive statistical analysis, chi-square testing and a multivariate analysis using a multinomial logistical model showed a significant correlation of younger age and female gender with tumour occurrence in the maxilla and the tongue. We provide a very detailed anatomical mapping of OSCC.

Head and neck squamous cell carcinoma (HNSCC) is frequently characterized by high resistance to radiotherapy, which critically depends on both altered signaling pathways within tumor cells and their dynamic interaction with the tumor microenvironment. This study evaluated the prognostic value of the phosphorylation status of AKT on Ser473 and Thr308 for the clinical outcome of patients with advanced HNSCC on radiotherapy. Furthermore, we investigated the impact of AKT(Ser473) phosphorylation [p-AKT(Ser473)] in the context of radioresistance using ex vivo tissue cultures that resemble the complex tissue architecture and paracrine interaction with the tumor microenvironment. In a cohort of 120 patients with advanced HNSCC, who were treated with primary or adjuvant radiotherapy, a significant association was found between relative p-AKT(Ser473) levels and overall survival (p = 0.006) as well as progression-free survival (p = 0.021), while no significant correlation was revealed for relative p-AKT(Thr308) levels. In ex vivo tissue cultures p-AKT(Ser473) levels were increased upon irradiation and treatment with the PI3K inhibitor LY294002 inhibited both basal and irradiation induced AKT(Ser473) phosphorylation. Strikingly, pretreatment with LY294002 sensitized tissue cultures derived from primary and recurrent tumors to radiotherapy as determined by impaired tumor cell proliferation and enhanced DNA damage. In conclusion, phosphorylation status of AKT(Ser473) in tumor specimens serves as a novel biomarker to identify patients with advanced HNSCC at high risk for treatment failure following radiotherapy, and our data from ex vivo tissue cultures support the assumption that pharmacological inhibition of AKT(Ser473) phosphorylation might circumvent radioresistance to improve efficiency and reduce toxicity of current treatment modalities.

Pancreatic acinar cell carcinomas (PACs) are rare but are distinct aggressive neoplasms that phenotypically differ from pancreatic ductal adenocarcinomas (PDACs) and pancreatic neuroendocrine neoplasms (PNENs). Despite recent work on the genetic changes of PACs, their molecular pathogenesis is still poorly understood. In this study, we focus on a comparative genomic hybridization analysis. Based on frequent chromosomal imbalances, the involvement of DCC and c-MYC in the pathogenesis of PACs is further investigated. Moreover, we examine markers harboring potential therapeutic relevance (K-RAS, BRAF, EGFR, MGMT, HSP90, L1CAM, Her2). PACs revealed a microsatellite stable, chromosomal unstable genotype, defined by recurrent chromosomal losses of 1p, 3p, 4q, 5q, 6q, 8p, 9p, 11q, 13q, 16q, and 18, as well as gains of 1q, 7, 8q, 12, 17q, and 20q. Subsets of PAC displayed reduction/loss of DCC (79 %) and c-MYC-amplification (17 %). Significant EGFR expression occurred in 42 %, HSP90 expression in 98 %, L1CAM expression in 72 %, and loss of MGMT in 26 %. Two cases carried a K-RAS mutation. Mutations of EGFR or BRAF were not detected. All cases were Her2/neu-negative. PACs display characteristic chromosomal imbalances which are distinctly different from those in pancreatic ductal adenocarcinomas and pancreatic neuroendocrine neoplasms. Our findings suggest that DCC and c-MYC alterations may play an important role in the pathogenesis of PACs. Furthermore, EGFR, MGMT, HSP90, and L1CAM may be useful as therapeutic markers and predictors of response to therapy in a subset of PACs.

p16(INK4a) immunohistochemical overexpression is an overall reliable surrogate marker of human papillomavirus (HPV)-associated head and neck squamous cell carcinomas (HNSCC). However, cases of ambiguous p16(INK4a) overexpression are regularly detected in the head and neck: p16(INK4a) expression can be observed in non-malignant tissue, such as tonsillar crypt epithelium and a proportion of branchial cleft cysts. Additionally, diverse patterns of p16(INK4) expression can complicate interpretation of "p16(INK4a) -positivity". These aspects impede the unrestricted application of p16(INK4a) as a diagnostic marker in the head and neck. We hypothesized that combined detection of p16(INK4a) and the proliferation marker Ki-67 could support clarification of ambiguous p16(INK4a) expression in the head and neck by specifically indicating p16(INK4a) -expressing cells with proliferative activity. p16(INK4a) /Ki-67 co-expression in a combined staining procedure was correlated to distinct p16(INK4a) expression patterns and HPV status (HPV DNA followed by E6*I oncogene mRNA detection) in 147 HNSCC and 50 non-malignant head and neck samples. p16(INK4a) /Ki-67 co-expression only occurred in transformed cells of the head and neck. Co-expression was never detected in non-transformed cells. Combined p16(INK4a) /Ki-67 expression was stringently associated with a diffuse p16(INK4a) expression pattern. All HPV oncogene-expressing HNSCC showed p16(INK4a) /Ki-67 co-expression. We demonstrate that p16(INK4a) /Ki-67 co-expression occurs exclusively in transformed cells of the head and neck. Our findings indicate a substantial impact of combined p16(INK4a) /Ki-67 expression in the assessment of ambiguous p16(INK4a) expression in the head and neck by specifically identifying p16(INK4a) -expressing cells with proliferative activity. This property will be of considerable significance for head and neck histo- and cytopathology.

Twenty to thirty per cent of wisdom teeth are partially or completely retained. A displacement of such teeth into the ascending ramus of the mandible is far less frequent with few reported cases in the literature. The case of a young lady and a review of the literature are presented. A 27-year-old woman was referred to the specialist department by her dentist. At the age of 22, a panoramic radiograph had been taken for an agenesis of the patient's lower left second molar. At this time, the lower left third molar was situated slightly submucosally at the angle of the mandible. In the present radiograph, the tooth had migrated into the ascending ramus of the mandible. Clinically, there was no pain, sensation disorder, disturbed occlusion, limited mouth opening or any other complaint. Due to significant tooth migration within the last 6 years, operative removal of the displaced tooth was recommended. Computed tomography showed that the distal root was in direct relation with the inferior alveolar nerve. Treatment was performed via a transoral approach. Post-operative follow-up was uneventful. This case stresses the importance of long-time follow-up of retained teeth and their immense potential for migration.

Background Extensive bone augmentation procedures are frequently performed prior to implant surgery. To achieve tension-free wound closure at the grafted site and thus avoid dehiscence and exposure or total loss of the bone graft, extensive soft tissue mobilization is required. In vitro studies have shown the potential of self-filling osmotic tissue expanders to optimize the amount of resulting soft tissue and vascularization of the recipient site. Purpose The purpose of this prospective clinical study was to evaluate the application and complication rate of osmotic hydrogel expanders inserted subperiosteally prior to bone grafting. Methods In this prospective observational study, eight patients were implanted with 11 intraoral osmotic hydrogel expanders prior to bone augmentation procedures. All expanders were placed in subperiosteal positions using the tunnel technique. The occurrence of soft tissue–related complications such as necrosis, perforation, infection, or wound dehiscence leading to expander loss was defined as the primary parameter for analysis and evaluation. Further clinical parameters were soft tissue quality and quantity as well as expansion duration. Results The expansion time depended upon defect size and expander dimensions. Complications, that is, perforation of the expanders through the oral mucosa, occurred in two patients (3 expanders) who suffered from extreme preoperative scarring in the treated areas owing to prior trauma in one patient and cleft surgery in the other. Patients were grafted with autologous (n = 7) or synthetic (n = 1) block grafts. The expanders were removed during bone grafting surgery. No further dehiscence occurred during the observation period, and all patients were treated successfully with dental implants and subsequent prosthetic reconstruction. Conclusions Within the limits of this observational clinical study, hydrogel expanders may help to generate additional soft tissue, and they might contribute to the overall improvement of the bone augmentation process by reducing the risk of complications related to the lack of soft tissue. Further randomized controlled studies are necessary.

Background PIK3CA alterations have been shown to be a frequent event in oropharyngeal squamous cell cancer (SCC), especially in human papillomavirus (HPV)-related tumors. Methods Tissue microarrays (TMAs) were used to evaluate pAKT(Ser473)/(Thr308), total protein kinase B (AKT)(pan) and phosphatase and tensin homolog (PTEN) expression in primary tumors and corresponding nodal disease in oropharyngeal SCC. The HPV status was determined in regard of HPV16 DNA and RNA. Survival analysis was performed by using Kaplan-Meier curves, log-rank testing, and multivariate Cox regression analysis. Results HPV16 is a prognostic predictive marker for advanced oropharyngeal SCC. pAKT(Ser473) and PTEN are highly expressed in HPV-related oropharyngeal SCCs in contrast to pAKT(Thr308). The pAKT(Ser473) expression increased from primary tumors to progressive nodal disease (21.1%; P < .011). Conclusion Activation of phosphoinositide 3-kinase (PI3K)/pAKT(Ser473) frequently occurs in advanced HPV-positive oropharyngeal SCC and elevated pAKT(Ser473) levels represent a feature during progression of oropharyngeal SCC, indicating a critical role of the mammalian target of rapamycin (mTOR) complex. Further studies are required to evaluate specific drugs targeting PI3K/AKT/mTOR in consideration of PIK3CA alterations.

Objectives Treatment of the severely atrophic maxilla with dental implants is challenging due to the insufficient horizontal and vertical bone volume and centripetal resorption pattern of the maxilla. Bone-augmentation procedures are often necessary prior to implant placement. The objective of this study was to assess the suitability of using calvarial bone grafts to enable implant placement in severely atrophic maxillae. Material and methods Seventeen patients with severe atrophic edentulous maxillae were reconstructed with autogenous calvarial bone grafts. After a 4-month healing period, the patients received a total of 134 dental implants, which were left to heal in submerged positions for 3 months before prosthetic rehabilitation was performed. Patients were followed clinically and radiographically for an average observation period of 53.94 months. Results At the intraoral recipient sites, two infections developed, causing partial loss of the respective bone grafts. Implant placement, however, was possible at all sites. No donor-site complications occurred. Two of 134 implants were lost in two patients prior to prosthetic loading. The implant survival rate was 98.51%. The implant success rate was 87.6%, and a mean marginal bone loss of 0.62 mm (SD 0.77 mm) was documented. Conclusions Patients with severe bone atrophy of the edentulous maxilla can be successfully reconstructed with calvarial bone grafts and dental implants and show a stable clinical and radiographic situation after a mean observation period of 53 months.

Tumours of the mandibular bone or adjacent soft tissue often necessitate mandibular resection. Subsequent primary bone reconstruction to achieve optimal functional and aesthetic results has been made possible by microvascular surgical techniques and now represents the international gold standard. Microvascular reanastomosis of autologous bone grafts from the iliac crest or fibula is the most common procedure for reconstruction of the mandible. The localisation and extent of the expected defect, as well as a patient's overall condition and ability to tolerate long surgical procedures must be carefully considered before deciding upon the course of treatment. Additional microvascular reanastomosis of soft tissue flaps and stereolithographic models facilitate preoperative planning and broaden the surgical spectrum. Following successful reconstruction of the bone, insertion of dental implants and prosthetic rebuilding are required to complete rehabilitation, including restoration of the patient's ability to chew and speak. The authors recommend specialised oncologic centres for such complex surgical reconstructions.

Background Insufficient bone height in the posterior maxilla is caused by bone atrophy after tooth extraction and continued pneumatization of the maxillary sinus. To allow for implant placement in this area, external sinus-floor elevations are performed. For this indication, the application of various bone graft materials can be a reliable alternative to autologous bone. Purpose The aim of this study was to analyze a nanoporous bone graft material under the condition of early implant treatment in sinus floor elevations. Materials and Methods Sixty-six patients received 94 individual external sinus-floor elevations as a precondition for implant surgery. As grafting material, a synthetic, nanoporous bone graft material consisting of a mixture of nano-hydroxyapatite and nano-β-tricalciumphosphate crystals, combined with blood from the defect side, was used. Depending on the remaining vertical bone height, implant placement was performed either simultaneously with bone augmentation or consecutively in a delayed approach. After a 4-month healing period, the patients received 218 implants and were followed up clinically, radiographically, and histologically. To quantify the bone situation at implant placement, immunohistochemical analysis using tenascin-C was performed. Results We achieved an average vertical bone increase of 8.28 mm (SD, 2.59) for the one-stage approach and 10.99 mm (SD, 1.73) for the two-stage approach after sinus-floor elevation. The augmented areas showed mean resorption rates of 10.32% (one stage) and 10.82% (two stages) of vertical graft during the observation period. Immunohistochemical analysis after 4 months of healing showed high tenascin activity, indicating bone growth. Good primary stability was achieved during implant placement. Mean peri-implant marginal bone loss was 0.45 mm (SD, 0.31). Conclusion After a mean observation time of 21.45 months, the biomaterial showed good osseointegration and bone stability radiographically. Adding to this the positive histological and immunohistochemical findings, we conclude that, after a relatively short 4-month healing period, the biomaterial showed predictable results.

Children with nonsyndromatic isolated metopic suture synostosis suffer from a significant deformity of the supraorbital ridges, the temporal regions and hypotelorism. We retrospectively analyzed 54 consecutive cases of isolated nonsyndromatic metopic synostosis treated over a 14-year-period. The data were evaluated using patients' clinical records, skull radiographs in two planes, CT-scans, MRI scans and pre-/post-operative photographs. Surgery with standardized fronto-orbital advancement was performed at a median age of 11.5 months. Follow-up ranged from 4.5 months to 177.4 months, with an average of 51.9 months. The average blood loss was less than 255ml and the average post-operative length of stay was 5 days. Not a single major complication was observed except for uncomplicated dural tears in six cases. According to the classification of Whitaker, results were considered good to excellent (Category I and II) in all except one case (Category IV). As the current techniques have been standardized for routine use, surgical risks are reasonably low with no mortality or permanent morbidity. We think that the treatment of single metopic synostosis is safe with very low reoperation rates and short length of hospital stay. Overall, our results showed acceptable minor complication rates and generally satisfactory aesthetic outcomes.

Objective and aim Severe cases of bone atrophy in the maxilla or mandible are often reconstructed using bone from extraoral donor sides. Most commonly, grafts from the iliac crest are used for augmentation, however, frequently associated with bone resorption as possible late complication. Calvarial bone grafts, often reported to show less resorption, are an alternative. The aim of this study was to compare the bone stability of vertical bone grafts from the iliac crest and the calvarium. Patients and methods Twenty-three patients receiving vertical onlay bone grafts were included in this retrospective cohort study. In nine patients alveolar ridge defects were treated with bone from the iliac crest. Fourteen patients were reconstructed using calvarial bone grafts. To quantify bone resorption, the data of digital panographs were evaluated. Radiographs were taken prior to bone grafting, after augmentation surgery, 6 months after bone healing, prior to implant surgery, after implant surgery and at yearly intervals thereafter. Results Postoperative complications at the recipient site occurred equally in both groups. The complication rate was 35.7% for the calvarial group and 33.3% in the iliac crest group. No donor-site complications were reported in either group. After bone augmentation procedure, a mean vertical bone gain of 8.55 mm (SD 5.96) was measured. Bone grafts from the iliac crest showed a significantly higher bone loss of 24.16% (SD 8.47) than grafts from the calvarium (8.44%, SD 3.64) at the time of implant placement (P = 0.0003). Implant survival was similar in both groups. Discussion Both bone-grafting approaches are successful and reliable techniques, enabling implant placement in even highly atrophied alveolar ridges and with identical implant survival rates, although bone resorption differs. Within the limitations of this study bone from the calvarium shows higher bone stability in the early healing phase.

Background. Surgically assisted rapid maxillary expansion (SARME) is a standardized method to treat cross bites in maxillofacial surgery. Changes to the nasal airways are assumed due to the anatomic dependence between the palate and the nasal floor. Patients and methods. In this study 19 patients with a transverse deficit of the upper jaw underwent SARME. CT scans were performed 1 month pre- and 6 months postoperatively. Effects to the lower nasal airways, the nasal septum and the hard palate were subsequently evaluated. Results. The mean distraction width of the upper jaws was 5.84 mm (SD 2.19) postoperatively. In addition to the dentoalveolar gain in width, a significant increase in the nasal floor was observed (p

Gene copy number aberrations are involved in oral squamous cell carcinoma (OSCC) development. To delineate candidate genes inside critical chromosomal regions, array-CGH was applied to 40 OSCC specimens using a microarray covering the whole human genome with an average resolution of 1 Mb. Gene copy number gains were predominantly found at 1q23 (9 cases), 3q26 (11), 5p15 (13), 7p11 (7), 8q24 (17), 11q13 (15), 14q32 (8), 19p13 (8), 19q12 (7), 19q13 (8), and 20q13 (9), whereas gene copy number losses were detected at 3p21-3p12 (15), 8p32 (11), 10p12 (8), and 18q21-q23 (10). Subsequent mRNA expression analyses by quantitative real time polymerase chain reaction found high mRNA expression of candidate genes SOX2 in 3q26.33, FSLT3 in 19p13.3, and CCNE1 in 19q12. Tissue microarray (TMA) analyses in a representative OSCC collection found gene copy number gain for SOX2 in 52% (115/223) and for CCNE1 in 31% (72/233) of the tumors. Immunohistochemical analyses on TMA sections of the corresponding proteins detected high expression of SOX2 in 18.1% (49/271) and of CyclinE1 in 23.3% (64/275) of tumors analyzed. These findings indicate that SOX2 and CCNE1 might be activated via gene copy number gain and participate in oral carcinogenesis. The combination of array-CGH with TMA analyses allows rapid pinpointing of novel promising candidate genes, which might be used as therapeutic stratification markers or target molecules for therapeutic interference.

Osteosarcomas are highly malignant tumours of bone, and are rare in the craniofacial area. They account for only 1% of all head and neck malignancies. In this study we describe the treatment of 12 patients who were diagnosed with osteosarcoma of the mandible or maxilla between 1990 and 2004. These patients were given interdisciplinary treatments, either with a combination of neoadjuvant and adjuvant high-dose chemotherapy following the protocol of the cooperative osteosarcoma study group (COSS) with radical excision of the tumour (n=7), with a combination of radiation and radical excision (n=2), or with radical excision alone of the tumour (n=3). The 5-year survival of the group treated only by excision was 1 of 3, whereas that of the group treated by combination of chemotherapy and surgical removal was 7 of 7. The two patients treated with radiation and excision also lived 5 years after the end of the treatment, but had side-effects of radiation, whereas those treated with chemotherapy had no serious side-effects. We therefore conclude that combined interdisciplinary treatment of radical resection of the tumour with high-dose chemotherapy according to standard protocols is the most effective treatment for craniofacial osteosarcomas.

Locally advanced operable oral squamous cell carcinoma (OSCC) continues to be a major therapeutic challenge despite the implementation of novel multi-modal treatment approaches. To improve local and local-regional control and to allow functional reconstruction after ablative surgery, neoadjuvant protocols have been developed during the last decade implementing radiochemotherapy prior to selective surgery. In the present retrospective analysis, the results of concurrent radiotherapy with 40 Gy and low-dose cisplatin-based chemotherapy followed by major surgery are presented for n = 207 patients with an OSCC of stage III or IV. The overall survival for all patients analyzed was 49.5% after 60 months and 37.0% after 120 months. Further subgroup analysis found that histopathologic N0 tumours had a significantly better 5-year and 10-year overall survival rate than N+ tumours (p = 0.004). In multivariate analysis, only postoperative N0 stage was a significant predictor for a favourable outcome (p = 0.004). Overall disease-free survival of the whole patient collective was 70.4% after 60 months and 62.6% after 120 months with superior 60 month and 120 month disease-free survival for T0 (p = 0.018) and N0 tumours (p = 0.007), which was verified by multivariate analysis (p = 0.019 and p = 0.055, respectively). T+ tumours inherited a 2.5-fold increased risk for the development of local or loco-regional failure (p = 0.05), and N+ tumours a 6.1-fold increased risk for the development of distant metastases (p

Background: Gene copy number gain of chromosomal arm 5p is frequently found in oral squamous cell carcinoma (OSCC) suggesting the activation of proto-oncogenes. TERT is a candidate gene encoding for human telomerase reverse transcriptase (hTERT). The aim of the present study was to elucidate the relevance of TERT copy number gain and high hTERT expression in OSCC. Methods: Fluorescence in situ hybridization (FISH) for TERT and immunohistochemistry (IHC) for hTERT were performed to analyze TERT copy numbers and hTERT expression, respectively, on tissue microarray (TMA) sections including n = 247 OSCC and n = 105 pharyngeal and laryngeal squamous cell carcinomas (PSCC/LSCC). Results: Increased hTERT protein expression was more frequently found in OSCC (71.1%, 155/218) than in PSCC/LSCC (36.0%, 35/89) (P

Despite new radiotherapeutic strategies, radioresistance in head and neck squamous cell carcinoma (HNSCC) remains a major problem. Preclinical model systems are needed to identify resistance mechanisms in this heterogeneous entity.We elucidated the interplay among mitogen-activated protein kinase (MAPK)-inhibition, radiation, and p53 mutations in vitro and in a novel ex vivo model derived from vital human HNSCC samples. HNSCC cell lines (p53WT/mut) were treated with the mitogen-activated protein kinase (MEK)-inhibitor PD-0325901 and subsequently irradiated. Radiosensitization was functionally assessed and evaluated in the ex vivo model.We observed a pronounced irradiation-induced extracellular signal-regulated kinase (ERK) phosphorylation in 2 cell lines, which was independent of their p53 mutation status and associated with PD-0325901-related radiosensitization in a clonogenic assay. Heterogeneity in irradiation-induced ERK phosphorylation and in radiosensitization after MEK-inhibition was also reflected in the ex vivo model.We provide experimental evidence for radiosensitizing effects of PD-0325901 in HNSCC. The ex vivo culture technology might offer a promising tool for individualized drug efficacy testing. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2049-E2061, 2016.

Oral squamous cell carcinoma (OSCC) is a solid neoplasm exhibiting aggressive tumor phenotypes with unpredictable biological behavior. Recent studies suggested that high expression of the antiapoptotic protein survivin might be associated with adverse outcome in oral cancer patients. To investigate, whether increased copy numbers of the survivin-encoding gene BIRC5 results in elevated survivin levels and whether BIRC5 and survivin could serve as progression markers in the clinical course of OSCC, tumor tissue microarray analysis was performed applying fluorescence in situ hybridization and immunohistochemistry to 296 OSCC specimens. Gene copy number gain of BIRC5 was detected in 33.9% (150/227) of cases, which correlated significantly with high UICC stage and the presence of lymph node metastases (p = 0.003 and p = 0.001, respectively), but not with unfavorable patients' outcome (p > 0.05) in multivariate analysis. High survivin expression was found in 67.3% (169/251) of cases to predict increased 5- and 10-year overall survival of patients in a multivariate model including UICC stage and age as covariables (p = 0.035 and p = 0.026, respectively). Within a subgroup of patients, who received radiation therapy (n = 121), high survivin expression was found to be the only predictor of favorable 3-, 5- and 10-year overall survival in a multivariate cox regression analysis including UICC stage and age as covariables (p = 0.001, p = 0.004 and p = 0.006, respectively). In conclusion, high survivin expression might be useful to identify OSCC patients, who would benefit from radiotherapy.

Adenoid cystic carcinoma (ACC) of the salivary gland is a neoplasm characterized by slow but inevitable local progression and terminal hematogenous metastasis. To detect novel imbalanced chromosomal regions associated with tumorigenesis, we used chromosomal comparative genomic hybridization to screen 27 ACC. The most common aberration was copy number gain of 22q13 (nine cases) followed by gains of 16p (seven cases) and 17q (four cases) and copy number losses on 6q (six cases). To further delineate the prevalence of 22q13 copy number gains in ACC, fluorescence in situ hybridization was performed for five bacterial/phage artificial chromosome (BAC/PAC) probes from the 22q13 consensus region with 57 ACC on a tissue microarray. The overall prevalence of copy number gains on 22q13 was 30% of the tumors in the fluorescence in situ hybridization analysis, irrespective of histologic differentiation (cribriform/tubular vs. solid) or tumor event (primary vs. recurrent). We therefore assume that copy number gain of 22q13 is a novel frequent finding in ACC that may be involved in the initial pathogenesis of this neoplasm by proto-oncogene activation.

Non-Hodgkin's lymphoma represents about 5% of all malignant lesions of the head and neck. In this study we retrospectively evaluated clinical presentation, histological subtype and long-term prognosis of 42 patients with non-Hodgkin's lymphoma involving the craniofacial area. The mean age at diagnosis was 64years. More than half of the patients presented with disseminated disease at multiple sites (55%, n =23). In 62% ( n =26) the first manifestation was extranodal. The most common affected region was the oral cavity (65%, n =17). Treatment consisted of local therapy, including surgical resection and radiation, as well as chemotherapy with or without local therapy. Recurrence occurred in 31% ( n =13) of the treated patients. Mean survival after first diagnosis varied from 17months in patients presenting with diffuse large B-cell lymphoma (DLBCL), to 8.5years in patients with follicular lymphoma. The most common histological subtype is DLBCL. Standard treatment for DLBCL consists of chemotherapy combined with CD 20 monoclonal antibody, even after total resection of the tumour. There is high risk of systemic disease in patients presenting with non-Hodgkin's lymphoma and high risk of post therapy recurrence.

Head and neck squamous cell carcinoma (HNSCC) is frequently characterized by high resistance to radiotherapy, which critically depends on both altered signaling pathways within tumor cells and their dynamic interaction with the tumor microenvironment.This review covers EGFR-phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT)-mechanistic target of rapamycin (mTOR) signaling in HNSCC. The role of each pathway node in radioresistance is discussed. Preclinical and clinical innovative aspects of targeting EGFR-PI3K-AKT and mTOR are demonstrated. Ongoing clinical trials and future perspectives are presented.Different cellular signaling pathways seem to mediate radioresistance in advanced HNSCC and various molecular targeted therapies are currently being investigated to sensitize tumor cells to radiotherapy. Recently, new insights in the mutational landscape of HNSCC unraveled critical alterations in putative oncogenes and tumor suppressor genes and have emphasized the importance of PI3K and the corresponding upstream and downstream signaling pathways in pathogenesis and treatment response. The frequent activation of the EGFR-PI3K-AKT-mTOR pathway in HNSCC and its implication in the context of radiosensitivity make this pathway one of the most promising targets in the therapy of HNSCC patients. Clinical studies targeting EGFR and mTOR in combination with radiotherapy are under investigation.

Plattenepithelkarzinome der Mundhohle haben trotz moderner adjuvanter und neoadjuvanter Therapieformen nach wie vor eine schlechte Prognose. Sie entwickeln sich aus normaler Mundschleimhaut uber einen mehrstufigen Prozess, zu dem u. a. Deletionen von Tumorsuppressorgenen und die Amplifikation von Onkogenen gehoren. Die molekularen und zellularen Ereignisse wahrend der klonalen Entwicklung eines invasiven Karzinoms sind komplex, und es existieren bis jetzt keine zytogenetischen Marker fur spezifische Stadien der Tumorentwicklung, die fur eine genauere Typisierung der Lasionen notwendig waren. In der vorliegenden Studie wird erstmals der Einsatz der neuartigen Gewebechiptechnologie bei 293 Plattenepithelkarzinomen der Mundhohle dargestellt. Untersucht wurden das Onkogen Cyclin D1 mittels Fluoreszenz-in-situ-Hybridisierung (FISH) sowie die Proteine Cyclin D1, p53, p16, CDK4, Bcl2, Mdm2, und Rb mittels Immunhistochemie (IHC). Die Gewebechiptechnologie erwies sich als ein verlassliches und schnelles Screeningverfahren zur Charakterisierung von molekularen und zellularen Veranderungen bei Mundhohlenkarzinomen.

Infantile myofibromatosis is a proliferative disorder characterized by the development of single or multiple nodular lesions in the soft tissue, skeleton, and internal organs. These tumors can occur at any anatomic site, but in one third of the cases, the head and neck region is involved. Here, we report a case of an infantile myofibroma occurring in a 7-year-old girl presented as a solitary lesion in the head and neck area. The clinical heterogeneity and the misleading histopathologic appearances may render the diagnosis difficult. Usually, treatment of choice is surgical removal of the tumor; however, the low rate of recurrence and the possibility of spontaneous regression may lead to conservative surgery or therapeutic abstention.

Recurrent gain on chromosome 3q26 encompassing the gene locus for the transcription factor SOX2 is a frequent event in human squamous cell carcinoma, including head and neck squamous cell carcinoma (HNSCC). Numerous studies demonstrated that SOX2 expression and function is related to distinct aspects of tumor cell pathophysiology. However, the underlying molecular mechanisms are not well understood, and the correlation between SOX2 expression and clinical outcome revealed conflicting data. Transcriptional profiling after silencing of SOX2 expression in a HNSCC cell line identified a set of up-regulated genes related to cell motility (e.g. VIM, FN1, CDH2). The inverse regulation of SOX2 and aforementioned genes was validated in 18 independent HNSCC cell lines from different anatomical sites. The inhibition of cell migration and invasion by SOX2 was confirmed by constant or conditional gene silencing and accelerated motility of HNSCC cells after SOX2 silencing was partially reverted by down-regulation of vimentin. In a retrospective study, SOX2 expression was determined by immunohistochemical staining on tissue microarrays containing primary tumor specimens of two independent HNSCC patient cohorts. Low SOX2 expression was found in 19.3% and 44.9% of primary tumor specimens, respectively. Univariate analysis demonstrated a statistically significant correlation between low SOX2 protein levels and reduced progression-free survival (Cohort I 51 vs. 16 months; Cohort II 33 vs. 12 months) and overall survival (Cohort I 150 vs. 37 months; Cohort II 33 vs. 16 months). Multivariate Cox proportional hazard model analysis confirmed that low SOX2 expression serves as an independent prognostic marker for HNSCC patients. We conclude that SOX2 inhibits tumor cell motility in HNSCC cells and that low SOX2 expression serves as a prognosticator to identify HNSCC patients at high risk for treatment failure.

Head and neck squamous cell carcinoma (HNSCC) is frequently characterized by high resistance to radiotherapy, which critically depends on both altered signaling pathways within tumor cells and their dynamic interaction with the tumor microenvironment. This study evaluated the prognostic value of the phosphorylation status of AKT on Ser473 and Thr308 for the clinical outcome of patients with advanced HNSCC on radiotherapy. Furthermore, we investigated the impact of AKT(Ser473) phosphorylation [p-AKT(Ser473)] in the context of radioresistance using ex vivo tissue cultures that resemble the complex tissue architecture and paracrine interaction with the tumor microenvironment. In a cohort of 120 patients with advanced HNSCC, who were treated with primary or adjuvant radiotherapy, a significant association was found between relative p-AKT(Ser473) levels and overall survival (p = 0.006) as well as progression-free survival (p = 0.021), while no significant correlation was revealed for relative p-AKT(Thr308) levels. In ex vivo tissue cultures p-AKT(Ser473) levels were increased upon irradiation and treatment with the PI3K inhibitor LY294002 inhibited both basal and irradiation induced AKT(Ser473) phosphorylation. Strikingly, pretreatment with LY294002 sensitized tissue cultures derived from primary and recurrent tumors to radiotherapy as determined by impaired tumor cell proliferation and enhanced DNA damage. In conclusion, phosphorylation status of AKT(Ser473) in tumor specimens serves as a novel biomarker to identify patients with advanced HNSCC at high risk for treatment failure following radiotherapy, and our data from ex vivo tissue cultures support the assumption that pharmacological inhibition of AKT(Ser473) phosphorylation might circumvent radioresistance to improve efficiency and reduce toxicity of current treatment modalities.

p16(INK4a) immunohistochemical overexpression is an overall reliable surrogate marker of human papillomavirus (HPV)-associated head and neck squamous cell carcinomas (HNSCC). However, cases of ambiguous p16(INK4a) overexpression are regularly detected in the head and neck: p16(INK4a) expression can be observed in non-malignant tissue, such as tonsillar crypt epithelium and a proportion of branchial cleft cysts. Additionally, diverse patterns of p16(INK4) expression can complicate interpretation of "p16(INK4a) -positivity". These aspects impede the unrestricted application of p16(INK4a) as a diagnostic marker in the head and neck. We hypothesized that combined detection of p16(INK4a) and the proliferation marker Ki-67 could support clarification of ambiguous p16(INK4a) expression in the head and neck by specifically indicating p16(INK4a) -expressing cells with proliferative activity. p16(INK4a) /Ki-67 co-expression in a combined staining procedure was correlated to distinct p16(INK4a) expression patterns and HPV status (HPV DNA followed by E6*I oncogene mRNA detection) in 147 HNSCC and 50 non-malignant head and neck samples. p16(INK4a) /Ki-67 co-expression only occurred in transformed cells of the head and neck. Co-expression was never detected in non-transformed cells. Combined p16(INK4a) /Ki-67 expression was stringently associated with a diffuse p16(INK4a) expression pattern. All HPV oncogene-expressing HNSCC showed p16(INK4a) /Ki-67 co-expression. We demonstrate that p16(INK4a) /Ki-67 co-expression occurs exclusively in transformed cells of the head and neck. Our findings indicate a substantial impact of combined p16(INK4a) /Ki-67 expression in the assessment of ambiguous p16(INK4a) expression in the head and neck by specifically identifying p16(INK4a) -expressing cells with proliferative activity. This property will be of considerable significance for head and neck histo- and cytopathology.

Extensive bone augmentation procedures are frequently performed prior to implant surgery. To achieve tension-free wound closure at the grafted site and thus avoid dehiscence and exposure or total loss of the bone graft, extensive soft tissue mobilization is required. In vitro studies have shown the potential of self-filling osmotic tissue expanders to optimize the amount of resulting soft tissue and vascularization of the recipient site.The purpose of this prospective clinical study was to evaluate the application and complication rate of osmotic hydrogel expanders inserted subperiosteally prior to bone grafting.In this prospective observational study, eight patients were implanted with 11 intraoral osmotic hydrogel expanders prior to bone augmentation procedures. All expanders were placed in subperiosteal positions using the tunnel technique. The occurrence of soft tissue-related complications such as necrosis, perforation, infection, or wound dehiscence leading to expander loss was defined as the primary parameter for analysis and evaluation. Further clinical parameters were soft tissue quality and quantity as well as expansion duration.The expansion time depended upon defect size and expander dimensions. Complications, that is, perforation of the expanders through the oral mucosa, occurred in two patients (3 expanders) who suffered from extreme preoperative scarring in the treated areas owing to prior trauma in one patient and cleft surgery in the other. Patients were grafted with autologous (n = 7) or synthetic (n = 1) block grafts. The expanders were removed during bone grafting surgery. No further dehiscence occurred during the observation period, and all patients were treated successfully with dental implants and subsequent prosthetic reconstruction.Within the limits of this observational clinical study, hydrogel expanders may help to generate additional soft tissue, and they might contribute to the overall improvement of the bone augmentation process by reducing the risk of complications related to the lack of soft tissue. Further randomized controlled studies are necessary.

Objectives Patients with continuous bone defects of the mandible after ablative tumor surgery need bony reconstruction for proper function and aesthetics. Free microvascular reanastomized bone grafts provide a clinically proven option for such patients, yet the optimal source of donor tissue has not yet been established. The aim of this study was to evaluate and compare the bone volume stability of vascularized bone grafts, particularly in the early highly resorptive phase, from the iliac crest (DCIA) and the fibula and to assess the implantologic rehabilitations. Materials and methods Thirty-six patients with mandibular continuity defects due to tumor resection were reconstructed by the use of vascularized bone grafts; 21 patients received DCIA flaps and 15 patients received a composite free fibular flap, depending on the size and location of the defect. Bone resorption was assessed using digital panographs. Radiographs were taken immediately after bone reconstruction, 6 months postoperatively, prior to implant surgery, and at prosthetic loading. Results After a mean observation period of 6 months, vertical bone resorption was 6.79% for the patients of the iliac crest group (DCIA), 10.20% after 11 months, and 12.58% after 17 months. Fibular grafts showed a bone resorption of 5.30% after a mean observation time of 6 months, 8.26% after 11 months, and 16.95% after 17 months. Eighteen patients received 71 implants for implant-retained dental reconstructions. Conclusions Microvascular reanastomized bone grafts represent a reliable treatment option for reconstruction in cases of large defects of the mandible, with low graft resorption in the early healing phase. Additionally, the compared grafts provide sufficient bone volume to permit implant rehabilitation.

Summary Objectives The aim of the present study was to identify HPV-attributable SCC of the oral cavity (OSCC) in a cohort of patients from southern Germany. Materials and methods A sensitive PCR-enzyme immunoassay (EIA) was followed by a more specific in situ hybridization (ISH) to detect high risk human papillomavirus (HPV). An immunohistochemical dual-staining for p16INK4a and the proliferation marker Ki-67 was used to assess whether co-expression of p16INK4a/Ki-67 is a better surrogate marker for HPV in OSCC than p16INK4a alone, based on the hypothesis that combined p16INK4a and Ki-67 expression might specifically discriminate oncogene-induced p16INK4a expression from cell-cycle arrest-inducing senescence-associated p16INK4a expression. Results HPV-DNA by PCR–EIA could be detected in 25.1% (69/275) of the tumors, but ISH was negative in all of them. Diffuse p16INK4a overexpression was detected in 11 HPV PCR-positive tumors, but also in 6 HPV PCR-negative tumors. p16INK4a-expressing cells in diffusely positive tumors co-expressed Ki-67, irrespective of the HPV status. Neither the sole HPV status nor combined HPV/p16INK4a status nor the sole p16INK4a status was significantly associated with disease free or overall survival, however a trend towards better overall survival of patients whose tumor expressed p16INK4a in a focal pattern (=p16INK4a-positive/Ki-67-negative cells) compared to no p16INK4a expression (p = 0.09) was observed. Conclusion Viral DNA can be detected in some tumors by a sensitive PCR, but absence of ISH signals indicates that the HPV-attributable fraction is smaller than estimated from PCR positivity. p16INK4a/Ki-67 co-expression is detectable in a fraction of OSCC irrespective of the HPV status.

The reconstruction of hard and soft tissue defects, mainly after ablative oncologic surgery in the head and neck area, is an evolving field. The use of free flaps for reconstruction of the head and neck is considered to be the surgical standard. In our analysis of more than 1000 free flaps we give an overview of the development of the use of different types of free tissue transfer to the head and neck area over the last 25 years. We show that the evolving field of head and neck reconstruction raises new possibilities with new types of flaps, whereas other types of flaps disappear in the everyday clinical use. The spectrum of reconstruction possibilities broadens with the number of different flap types available to the head and neck surgeon.

As the traditional risk factors for oral squamous cell carcinoma, especially tobacco, decline, new potential causative agents become the focus of research. Since the discovery of human papillomavirus (HPV) and its importance in carcinogenesis in cervical cancer, a lot of research has been undertaken to define its role in different types of cancer. In the present study, we evaluate the role of high-risk HPV types in initiation and progression of oral squamous cell carcinoma (OSCC) using a systematic review of the current literature.A literature research with the search term "HPV oral squamous cell carcinoma" was performed via PubMed. Results were screened systematically for relevance and classified into the following categories: molecular biology, genetics, clinical aspects, and prevalence. Articles were then further analyzed to assess quality.The literature research led to 527 results, with an overall HPV prevalence of 30.1 % in OSCCs. The most frequently identified subtypes were HPV-16 and HPV-18 (25.4 and 18.1 %, respectively). Prognostic relevance of HPV was discussed controversially. HPV detection via polymerase chain reaction is the most established method today. Molecular changes according to carcinogenic pathways described for cervix carcinoma were not routinely found in OSCC. In general, no definite role of high-risk HPV is currently deducible from the literature.High-risk subtypes 16 and 18 are present in the genome in approximately one third of OSCC. Its role as a causative agent is less clear than the role in oropharyngeal tumors. The infection might not be the cause of carcinogenesis in a significant number of patients but may become proportionally more important with the decrease of the classical risk factors of tobacco and alcohol.

Insufficient bone height in the posterior maxilla is caused by bone atrophy after tooth extraction and continued pneumatization of the maxillary sinus. To allow for implant placement in this area, external sinus-floor elevations are performed. For this indication, the application of various bone graft materials can be a reliable alternative to autologous bone.The aim of this study was to analyze a nanoporous bone graft material under the condition of early implant treatment in sinus floor elevations.Sixty-six patients received 94 individual external sinus-floor elevations as a precondition for implant surgery. As grafting material, a synthetic, nanoporous bone graft material consisting of a mixture of nano-hydroxyapatite and nano-β-tricalciumphosphate crystals, combined with blood from the defect side, was used. Depending on the remaining vertical bone height, implant placement was performed either simultaneously with bone augmentation or consecutively in a delayed approach. After a 4-month healing period, the patients received 218 implants and were followed up clinically, radiographically, and histologically. To quantify the bone situation at implant placement, immunohistochemical analysis using tenascin-C was performed.We achieved an average vertical bone increase of 8.28 mm (SD, 2.59) for the one-stage approach and 10.99 mm (SD, 1.73) for the two-stage approach after sinus-floor elevation. The augmented areas showed mean resorption rates of 10.32% (one stage) and 10.82% (two stages) of vertical graft during the observation period. Immunohistochemical analysis after 4 months of healing showed high tenascin activity, indicating bone growth. Good primary stability was achieved during implant placement. Mean peri-implant marginal bone loss was 0.45 mm (SD, 0.31).After a mean observation time of 21.45 months, the biomaterial showed good osseointegration and bone stability radiographically. Adding to this the positive histological and immunohistochemical findings, we conclude that, after a relatively short 4-month healing period, the biomaterial showed predictable results.

The prognostic relevance of Ki-67 expression in oral squamous cell carcinoma (OSCC) is still controversial. As proliferating cells are more susceptible to ionizing radiation, the authors investigated if a high proliferation rate reflected by Ki-67 expression, predicts radiosensitivity in OSCC patients. In 52 patients with OSCC who received primary surgery followed by radiation therapy, the proliferation rate was assessed by Ki-67 immunhistochemistry and correlated to recurrent free survival and overall survival. Low proliferative carcinomas showed a significantly shorter mean time to recurrence of 27.5 months compared to 49.5 months of high proliferative tumours (p=0.048). The 5-year survival rate of low proliferative tumours was 49% compared to 80% for high proliferative tumours (p=0.042). This study indicates that tumours with high proliferative activity are more susceptible to radiation therapy. Ki-67 might be used as a marker to predict the response to radiation therapy in patients with OSCC.

Severely atrophied alveolar ridges are most commonly reconstructed with free autologous bone grafts from the iliac crest. The use of these grafts, however, is frequently associated with bone resorption as possible late complication after implant surgery and prosthetic loading. Other donor sites, especially intraoral donor sites, show limited availability. The aim of this present study was to evaluate the clinical and radiographical outcome of alveolar ridge reconstruction with bone from the calvarium and subsequent implant rehabilitation.Reconstruction was performed by using calvarial split grafts in case of severe and complex alveolar ridge defects induced by trauma or bone atrophy. Fifteen patients were treated at 19 different intraoral recipient sites (15 sites in the maxilla, four in the mandible). Autologous block grafts were used for combined vertical and horizontal grafting. After a 3-month healing period, patients received dental implants. A total of 99 dental implants (OsseoSpeed™, Astra Tech AB, Mölndal, Sweden) were inserted and left to heal in a submerged position for 3 months before the prosthetic implant-based rehabilitation was performed.No donor site complications occurred during or after surgery. At the intraoral recipient sites two infections occurred, leading to partial loss of the grafts. Implant placement, however, was possible in all cases. Two of 99 implants were lost in two patients prior to prosthetic loading. Patients were followed up clinically and radiographically for an average observation period of 28 months. Implant survival rate and success rates were 97.85 and 95.7%, respectively, and a minimal marginal bone loss was documented.The low morbidity at the donor sites and the good marginal bone stability in the reconstructed regions indicate that calvarial bone grafts represent a viable treatment alternative to grafts from the iliac crest.

This report focuses on the association between oral health-related quality of life (OHRQoL) and depression/anxiety of a homogeneous group of cancer patients who were recurrence-free for 8 years after treatment for advanced oral squamous cell. Participants were 24 patients (mean age 55 years, 75% men) treated with neoadjuvant concurrent radiochemotherapy followed by surgery with a mean recurrence-free period of 95 months (from 39 to 164 months). The OHRQoL (OHIP) and the anxiety/depression (HADS) were assessed twice (1 year between t1 and t2). OHRQoL was impaired in this group (mean OHIP score 65 units). In cross-lagged correlation analysis, the correlation between OHRQoL to t1 and depression to t2 was significant and greater than the non-significant correlation for depression to t1 and OHRQoL to t2 indicating that OHRQoL predicts depression better than vice versa. However, the difference in the correlation coefficients was not significant (ZPF-test). The same was true for OHRQoL and anxiety. The OHRQoL measured with the OHIP was impaired in comparison to the normal population. In the limitations of the study design and bearing the small sample size in mind, the results give evidence that OHRQoL predicts psychological outcomes, namely depression and anxiety, better than vice versa.

Despite its common histology and presentation, oral squamous cell carcinoma (OSCC) is associated with widely varying clinical behaviour and response to therapy. To further elucidate the molecular basis of OSCC, an approach for gene expression analysis termed comparative expressed sequence hybridization (CESH) was used in the present study. This straightforward approach allows the rapid delineation of pathophysiologically interesting candidate chromosome regions by a direct detection of aberrant transcriptional activation. CESH profiling of OSCC specimens led to the identification of several novel chromosomal regions. Increased expression compared to a set of control mucosa specimens was found on 1q22-q23, 3q26.3-qter, 4q31.1-q32, 11q12-q13.2, 14q32, 18q12, 19q13.2-q13.3 and 22q13.1-q13.2. Decreased expression was found on 8p22-p23, 16p12 and 16q23-q24. Using CESH, common patterns of altered sequence expression in different OSCC samples were obtained. While some of these regions overlap with those known to be frequently altered in OSCC on the genomic level, this screen revealed novel chromosome subregions with increased transcriptional activity, which are probably independent of the genomic status of the tumor cells.

The adequate treatment of the neck in early, clinically node-negative oral squamous cell carcinoma (OSCC) remains controversial. To assess whether elective supraomohyoid neck dissection is reasonable and efficient in early, locally circumscribed OSCC, the outcomes of treatment of 122 patients with an OSCC of clinical UICC stage I or II were retrospectively analysed in this study. Occult lymph node metastases were detected in 13.9% (17/122) of cases. They were more frequently found in T2 compared to T1 tumours (19.7% (14/71) vs. 5.9% (3/51), p=0.03), age, gender and grading had no influence on the prevalence of occult lymph node metastases (all p-values>0.05) in a multivariate logistic regression model. Subsequent multivariate survival analysis found that the presence of occult metastases was an independent predictor of reduced disease-free survival after 5 years (82.2% vs. 62.5%, p=0.004, and 61.9% vs. 17.8%, p

In this study we analysed the long-term prognosis of 52 patients with distant metastases to the craniofacial area. All patients were treated in our department between 1989 and 2009. Possible predictive factors for the overall survival prognosis like age, gender, histopathological type of the metastasis, location and tissue structure of the area in the head and neck region, time between primary tumour and metastasis and the therapy were evaluated. 62% of the patients with distant metastases in the craniofacial area were male (32/52), the average age was 63 years. Adenocarcinoma was the most common histological type (20/52) and lung (12/52), malignant melanoma of the skin (9/52) and breast (8/52) the most common primary tumour site. In 35% of all patients, the primary tumour was not known at the time of the diagnosis of the craniofacial metastasis, this number reduced to 17% without the patients with a CUP syndrome. Patients survived an average of 14.4 months after manifestation of the metastases and 43.4 months after the manifestation of the primary tumour.

Different devices are available to aid surgically-assisted maxillary expansion. In this study we have evaluated the changes to the anchoring teeth, the hard palate, and the lower nasal passage made by tooth-borne distraction devices. Thirty-one patients (mean (SD) age 28 (2) years) with deficiencies in the transverse width of the maxilla were examined by computed tomography and cone beam scans before and after operation. The data were analysed with the help of Wilcoxon's signed rank test and Spearman's r correlation. The mean (SD) distraction width was 6.5 (2.3) mm. All anchorage teeth were tilted (p

Different devices to perform a mandibular symphyseal distraction osteogenesis (MSDO) are available. This study evaluates how tooth borne distraction devices change to the teeth, the mandible and the condyles.19 patients (mean age 27.1) with anterior width deficiencies of the mandible were examined with routine pre- and postoperative CT-scans 1 month before and 4 months after a mean distraction width of 5.68 mm (SD 0.88). The anchorage teeth of the tooth borne device were examined concerning displacement of their axes as well as the movement of the condyles and the mandibular symphysis. The data were evaluated using Wilcoxon signed rank test and Spearman rho correlation.Significant tilting of the anchorage teeth was observed (p0.01). The axes changed by 3.32° (SD 1.57) in the first premolar and by 2.63° (SD 1.75) in the first molar. A total of 2.67 mm (SD 1.17) of bone was formed on the symphysis. A significant correlation was found between distraction width and intercoronal distance changes of the anchorage teeth (p0.01). No significant change of the intercondylar distance was found pre- and postoperatively in the Wilcoxon test.MSDO with tooth borne devices has strong effects on the anchorage teeth. No severe effects on the condyles were observed. The postoperative width gain is a result of newly generated bone in the symphysis and tooth tilting. Nevertheless stable postoperative bite corrections are achievable.

Dermatofibrosarcoma protuberans (DFSP) is a low-grade malignant neoplasm of the dermis that rarely manifests in the craniofacial area. In this retrospective analysis, we investigated the long-term survival of 7 patients with recurrent craniofacial DFSP. This study includes all patients in our department with recurrences of DFSP between 1989 and 2006. All patients were treated by radical surgery with 1-cm free safety margin in every direction and remained in routine long-term follow-up for tumor patients. Two of the 7 patients showed a local recurrence, which was again successfully treated surgically with the same technique. Advanced reconstruction with free full-thickness skin transfers, regional flaps, and forearm flaps, respectively, was required in 5 of the 7 patients. The other 2 patients were reconstructed locally. The long-term prognosis of craniofacial DFSP can be assessed optimistically even if the tumor already reoccurred. All 7 patients included in this study are still alive and so far not suffering from local recurrence. Advanced reconstructive techniques are often required in the management of reoccurring craniofacial DFSP. Late recurrences have been reported; therefore, a long-term follow-up for these patients should be considered.

Haemangiopericytomas (HPCs) found in bony structures are rare sarcomas of vascular origin. Here, we report the case of a 41-year-old female with a HPC originating in the right ramus of the mandible. After tumour staging and biopsy for histological reference the tumour was surgically removed. The surgical technique is described and therapy options of these rare cases are discussed and compared with these cases already documented. To the best of our knowledge, this is the 6th case of mandibular HPC reported in the literature.

Patients with oral squamous cell carcinoma (OSCC) and poor prognosis may benefit from an intensification of the initial therapy scheme. To improve the clinical management of these patients, there is a strong requirement for an accurate assessment of the malignant properties of the individual lesion. The objective of the present analysis was to define the potential value of 2-[(18)F]fluoro-2-deoxy-d-glucose ((18)FDG) uptake in the tumor measured by positron emission tomography (PET) in predicting patients' outcome in the clinical course of OSCC. In this respect, a clinically well-defined cohort of 79 patients with primary OSCC was retrospectively evaluated. (18)FDG uptake in the primary tumor site was quantified by calculation of the maximum standardized uptake values (SUV(max)). Subsequent statistical analyses found, that (18)FDG uptake of the primary tumor was significantly higher in stage T3/T4 vs. T1/T2 (p

Gene copy number gain of chromosomal arm 5p is frequently found in oral squamous cell carcinoma (OSCC) suggesting the activation of proto-oncogenes. TERT is a candidate gene encoding for human telomerase reverse transcriptase (hTERT). The aim of the present study was to elucidate the relevance of TERT copy number gain and high hTERT expression in OSCC.Fluorescence in situ hybridization (FISH) for TERT and immunohistochemistry (IHC) for hTERT were performed to analyze TERT copy numbers and hTERT expression, respectively, on tissue microarray (TMA) sections including n = 247 OSCC and n = 105 pharyngeal and laryngeal squamous cell carcinomas (PSCC/LSCC).Increased hTERT protein expression was more frequently found in OSCC (71.1%, 155/218) than in PSCC/LSCC (36.0%, 35/89) (P0.001). By contrast, specific TERT amplifications were less common in OSCC (2.1%, 4/191) compared with PSCC/LSCC (9.9%, 8/81) (P = 0.047).High hTERT expression is a frequent finding in OSCC. It might be a promising target for the development of specific anti-neoplastic therapy approaches.

Oral squamous cell carcinoma (OSCC) is a solid neoplasm exhibiting aggressive tumor phenotypes with unpredictable biological behavior. Recent studies suggested that high expression of the antiapoptotic protein survivin might be associated with adverse outcome in oral cancer patients. To investigate, whether increased copy numbers of the survivin-encoding gene BIRC5 results in elevated survivin levels and whether BIRC5 and survivin could serve as progression markers in the clinical course of OSCC, tumor tissue microarray analysis was performed applying fluorescence in situ hybridization and immunohistochemistry to 296 OSCC specimens. Gene copy number gain of BIRC5 was detected in 33.9% (150/227) of cases, which correlated significantly with high UICC stage and the presence of lymph node metastases (p = 0.003 and p = 0.001, respectively), but not with unfavorable patients' outcome (p0.05) in multivariate analysis. High survivin expression was found in 67.3% (169/251) of cases to predict increased 5- and 10-year overall survival of patients in a multivariate model including UICC stage and age as covariables (p = 0.035 and p = 0.026, respectively). Within a subgroup of patients, who received radiation therapy (n = 121), high survivin expression was found to be the only predictor of favorable 3-, 5- and 10-year overall survival in a multivariate cox regression analysis including UICC stage and age as covariables (p = 0.001, p = 0.004 and p = 0.006, respectively). In conclusion, high survivin expression might be useful to identify OSCC patients, who would benefit from radiotherapy.

Craniosynostoses are the most frequent craniofacial malformations. However, with a prevalence of 3–6 cases per 10,000 live births they are amongst the rarely seen diseases and their definite diagnosis thus poses a challenge to the physician. When an abnormal calvarial configuration is detected, a radiological evaluation is necessary to characterize the deformity and to guide the corrective surgical procedure. The demand for clear diagnostic criteria is justified by the severity of the disease and the possible consequences of delayed diagnosis. In addition to the clinical signs (deformation of the head), conventional skull X-rays show typical radiological alterations and are used for basic diagnostics. Diagnostic tests that may be performed to confirm the diagnosis and assess the extent of the problem, include computed tomography (CT), 3D-CT, magnetic resonance imaging (MRI) scans, and ultrasonography. In the present review we will describe the most important clinical and radiological characteristics of craniosynostosis by means of clinical, radiological and operative situs examples.