Aberrant expression of p53, p16INK4a and Ki-67 as basic biomarker for malignant progression of oral leukoplakias.

BACKGROUND: The risk of malignant progression of oral leukoplakia with and without dysplasia is unpredictable. MATERIALS AND METHODS: Leukoplakias without dysplasia of 35 patients, leukoplakias with dysplasia of 4 patients, and similar lesions obtained from tumor patients were retrospectively examined by immunohistochemistry for the expression of the proteins pRb, p53, p16(INK4a), Cyclin D1 and Ki-67. The predictive power of combined aberrant expression patterns for the progression of leukoplakias without dysplasia was examined. RESULTS: Increased expression of p53, Ki-67 and Cyclin D1, and loss of p16(INK4a) occurred in 45.9%, 38.9%, 29.4% and 32.4% of the leukoplakias without dysplasia, respectively. All alterations increased with progression but had poor positive predictive value. However, the combined p53/p16(INK4a)/Ki-67 aberration occurred in only three (9%) cases, of which two patients (66.7%) experienced progression to dysplasia and carcinoma in situ. The combined p53/p16(INK4a)/Ki-67 alteration had a negative predictive value (NPV) and sensitivity of 100%, specificity of 97% and positive predictive value (PPV) of 67%. By contrast, the combined p53/p16(INK4a)/Cyclin D1 alteration had 97% NPV and sensitivity of 50%, specificity of 90% and only 25% PPV. Loss of pRb and concomitant overexpression of p16(INK4a) were not observed arguing against an involvement of HPV in oral leukoplakia. CONCLUSIONS: We propose the combined p53/p16(INK4a)/Ki-67 alteration as a basic marker to define high risk leukoplakia patients. Lesions not showing this alteration appear to be harmless. Future studies should validate these findings and search for proteins which can further improve the PPV of the proposed basic marker.

Recurrent copy number gain of transcription factor SOX2 and corresponding high protein expression in oral squamous cell carcinoma.

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.

APOS-antibiotic prophylaxis for preventing infectious complications in orthognathic surgery: study protocol for a phase III, multicentre, randomised, controlled, double blinded, clinical trial with two parallel study arms.

BACKGROUND: It is a constant debate among surgeons whether the use of prolonged postoperative antibiotics may reduce surgical site infection rates. As specific treatment guidelines are still lacking, many surgeons continue to use broad-spectrum antibiotics, causing not only increased costs but also contributing to the potential for antibiotic resistance. Hence, there is an urgent need for an appropriately designed prospective clinical trial, to investigate whether a prophylactic use of antibiotics after surgery actually decreases surgical site infections to a clinically relevant degree. METHODS: This study presents a multicentre, randomised, controlled, double-blinded, clinical trial with two parallel study arms to demonstrate that no postoperative antibiotic prophylaxis (AP) is not inferior to antibiotic prophylaxis with respect to surgical site infections in patients having undergone orthognathic surgery. The primary efficacy endpoint is defined as the occurrence of postoperative surgical site infections within 30 days of surgery. Secondary endpoints are further efficacy and subject-oriented parameters within 90 days after surgery. The entire trial is planned for 54 months, with an enrolment of 1420 patients over 39 months by 14 national participating centres. DISCUSSION: As a highly standardised procedure on an exceeding, healthy and young homogenous study population and identical processes all over the world, elective orthognathic surgery as clean-contaminated procedure provides comparable intervention groups with balanced baseline characteristics, comparable surgical duration, even when performed within multiple centres. Therefore, evaluating antibiotic prophylaxis after orthognathic surgery will be of high scientific value representable for other surgical procedures. TRIAL REGISTRATION: DRKS-German Clinical Trials Register- DRKS00022838 ; EudraCT No. 2020-001397-30. Registered on 29 March 2021.

Cytogenetic characterization of head and neck squamous cell carcinoma cell lines as model systems for the functional analyses of tumor-associated genes.

Head and neck squamous cell carcinoma (HNSCC) is a solid malignant neoplasm exhibiting aggressive phenotypes and high recurrence rates. To improve its clinical management, understanding the molecular basis of HNSCC development is of critical importance. For the investigation of tumor-associated genes, functional analyses in well-characterized tumor cell systems are required. To establish an experimental platform, a set of 20 HNSCC cell lines was screened for genetic imbalances by chromosomal comparative genomic hybridization (cCGH). Frequent DNA copy number gains were detected on 3q26.3-qter, 5p, 7p11-p13, 8q23-qter, 9p11-p13, 9q31-qter, 11q13 and 20q13.1, whereas copy number losses were found on 3p, 4p, 4q32.1-qter, 8p11-p12 and 18q22 in agreement with previous observations on genetic aberrations detected in primary HNSCC specimens. Subsequent mRNA expression analysis of 11q13 candidate genes CCND1 and CTTN revealed that HNSCC cell lines exhibiting a DNA copy number gain on 11q13 had a higher transcript level of CCND1 and CTTN compared with HNSCC cell lines without 11q13 copy number gain (P = 0.014 and P = 0.009, respectively). Furthermore, CCND1 and CTTN amplification as detected by fluorescence in situ hybridization correlated with protein expression as assessed by immunocytochemistry. In summary, the cytogenetic characterization illustrates that this set of HNSCC cell lines is representative for the HNSCC genome and provides tumor model systems for detailed analysis of genes with a possible role in the pathomechanism of head and neck tumors.

Recurrent craniofacial dermatofibrosarcoma protuberans: long-term prognosis after close surgical removal.

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.

Neoadjuvant concurrent radiochemotherapy followed by surgery in advanced oral squamous cell carcinoma (OSCC): a retrospective analysis of 207 patients.

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<0.001). In conclusion, neoadjuvant radiochemotherapy with 40 Gy and concurrent low-dose cisplatin monotherapy followed by selective surgery is a feasible and reliable therapy concept, which results in encouraging overall and disease-free survival rates for therapy responders and which reliably selects therapy non-responders by the histopathological assessment of the neck dissection preparation. Those therapy non-responders might profit from intensified systemic therapy approaches.

Recurrent FGFR1 amplification and high FGFR1 protein expression in oral squamous cell carcinoma (OSCC).

Chromosomal aberrations are known to have an impact on the initiation and progression of oral squamous cell carcinoma (OSCC), but individual genes involved in OSCC pathogenesis are poorly described. To elucidate the molecular events underlying oral carcinogenesis, a set of primary OSCC were screened for distinct genetic imbalances by means of array-based comparative genomic hybridisation. For this, a DNA array was used containing 812 genomic targets including oncogenes, tumour-suppressor genes and chromosomal regions frequently altered in human neoplasms. The most frequent aberrations were amplification of MYC, EGFR, CCND1 and PIK3CA, whereas deletions affected TRAILR1 and ATM. Furthermore, a distinct high-level amplification of the fibroblast growth factor receptor 1 (FGFR1) locus was detected in two cases. Detailed FISH analysis on OSCC tissue microarray sections revealed amplification prevalence for FGFR1 of 17.4% (16/92). Furthermore, FGFR1 protein analysis by immunohistochemistry on a TMA containing 178 OSCC found a high FGFR1 expression in tumours of early t-stadium and UICC stage (T1/2 vs. T3/4: p=0.002; SI-II vs. S III-IV: p=0.048). Our results indicate that an increase in FGFR1 expression contributes to oral carcinogenesis at an early stage of development.

A large ameloblastic fibro-odontoma of the right mandible.

The ameloblastic fibro-odontoma is a rare mixed odontogenic tumor. It occurs predominantly in children and young adults with no sex predilection and locates most often in the posterior segment of the mandible. A painless swelling is the most common clinical sign. Radiologically, ameloblastic fibro-odontoma shows a circumscribed radiolucency, which contains radio-opaque foci of various sizes and shapes. Histological examination reveals a fibrous soft tissue, islands of odontogenic epithelium and a disordered mixture of dental tissues. The tumor produces enamel or enamel matrix, dentin and cementum. The treatment of ameloblastic fibro-odontomas usually consists of enucleation or surgical curettage, which is possible due to their benign biological behaviour.

Recurrent NMYC copy number gain and high protein expression in basal cell carcinoma.

Formation of basal cell carcinoma (BCC) has been linked to deregulation in the sonic hedgehogh (Shh) signalling pathway. Though mutations of the genes, PTCH1 and SMO, are known to be involved in aberrant Shh signalling, the distinct downstream effectors of these genes are poorly described. Studies have indicated that the NMYC oncogene is a potential Shh downstream effector. To assess the expression of Nmyc protein and gene copy numbers of the NMYC gene locus in a representative BCC tumour collection, immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH) were performed on 273 BCC specimens of different growth patterns and anatomic localisations on tissue microarray (TMA) sections. High Nmyc protein expression was detected in 72.7% (160/220) of all BCC specimens. Strong Nmyc immunopositivity was more frequently found in infiltrative BCCs compared to nodular/superficial BCCs (p=0.005), and in BCCs of the head compared to BCCs of other anatomic localisations (p=0.021). The prevalence of NMYC copy number gains was 17.5% (37/211), including three tumours with nodular differentiation that exhibited a distinct high-level amplification of the NMYC locus. These data indicate that high expression of the Shh downstream mediator, Nmyc, is a frequent event in BCC, predominantly in more aggressive subtypes. Although the NMYC copy number gain found in a subset of cases might contribute to this aberrant Nmyc protein expression by a gene dosage effect, our data suggests that Nmyc protein can also be induced by aberrant Shh signalling, acting as an effector molecule of the Shh pathway. Novel systemic anti-sense NMYC inhibition strategies could be a promising option for therapy-refractory BCC.

Tissue microarray analysis reveals site-specific prevalence of oncogene amplifications in head and neck squamous cell carcinoma.

Fluorescence in situ hybridization was applied on a collection of 609 squamous cell carcinomas of the head and neck (HNSCCs),including 511 primary carcinomas of different clinical stage and anatomical localization and 98 recurrent carcinomas, second primary carcinomas, and regional metastases on a tissue microarray. The overall prevalence of amplifications of five oncogenes analyzed was 34.5% for CCND1, 12.7% for EGFR, 8.8% for MYC, 6.2% for ZNF217, and 3.6% for ERBB2. CCND1 amplifications were associated with the pharyngeal site in primary carcinomas (P < 0.001), whereas amplifications of ZNF217 were less frequent in pharyngeal carcinomas as compared with primary oral and laryngeal carcinomas (P = 0.02). The amplification pattern of these oncogenes suggests that different molecular pathways are involved in HNSCCs of different localizations.

Copy number gains on 22q13 in adenoid cystic carcinoma of the salivary gland revealed by comparative genomic hybridization and tissue microarray analysis.

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.

Differential KIT expression in histological subtypes of adenoid cystic carcinoma (ACC) of the salivary gland.

Adenoid cystic carcinoma (ACC) of the salivary gland is characterized by a prolonged but inevitably unfavorable clinical course. Recent studies suggested the transmembrane tyrosine kinase KIT to be involved in ACC pathogenesis. To investigate KIT expression in histologically defined subgroups of ACC and to clarify whether KIT gene copy number gain contributes to KIT overexpression, tumor tissue microarray sections including 55 ACC tumors were analyzed by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). The prevalence of positive KIT immunostaining was 89% (49/55). Strong immunostaining of KIT was only found in cribriform and tubular but never in solid subtypes (p=0.02). Average KIT staining intensity was higher in cribriform and tubular (n=37) compared to solid (n=18) ACC subtypes (p=0.005). FISH analysis revealed copy number gains of the KIT gene in 6.1% (3/49) of tumors analyzed. Our results implicate that specific KIT tyrosine kinase inhibitors such as imatinib, might be used in future therapeutic approaches against subgroups of ACC.

Feasibility report for retreatment of locally recurrent head-and-neck cancers by combined brachy-chemotherapy using frameless image-guided 3D interstitial brachytherapy.

PURPOSE: Brachytherapy re-irradiation may offer an alternative re-treatment of recurrent head-and-neck cancer even after previous full dose radiation therapy. The purposes of this study were to determine the feasibility and accuracy of frameless image-guided interstitial needle implantation. METHODS AND MATERIALS: Between January 2000 and March 2003, 14 patients with biopsy-proven locally recurrent head-and-neck-cancer were retreated after previous full dose irradiation with combined external beam-brachytherapy with concomitant chemotherapy. Brachytherapy needle implantation was virtually planned taking into account the surrounding risk structures. Needles were implanted using an adapted frameless navigation system. Chemoradiotherapy was followed by 2-4 courses of chemotherapy every fourth week starting 4 weeks after the end of brachytherapy. RESULTS: The 1- and 2-year local control rates were 78% and 57%, respectively. Local control was obtained in 8/14 patients. The actuarial 1- and 2-year survival rates were 83% and 64%, respectively. The median survival was 28 months after a median follow-up of 21 months (range, 8-53). Six weeks after brachytherapy, 1 patient developed localized soft tissue necrosis which did not require surgical intervention. No additional grade III or IV late toxicity was seen after re-irradiation. Mean deviation of image-guided needle implantation was 3.4 mm for each needle (SD, 1.9 mm; range, 0.5-14 mm). The mean deviation of all needles of an implant was 4.3 mm (range, 2.3-8.6 mm). CONCLUSIONS: These data demonstrate that pulsed-dose-rate brachytherapy in combination with sequential chemotherapy is effective and safe in re-irradiation of locally recurrent oropharyngeal carcinomas and can be offered to patients with curative intent. Image guidance allows virtual planning and navigated implantation of brachytherapy needles with regard to optimized needle distribution and risk structures.

The outcome of various cements in combination with titanium reconstruction plates after segmental resection of the mandible.

We report on 82 patients who had segmental resection of the mandible and immediate reconstruction with titanium plates, which were supplemented by polymethylmethacrylate cement (n=32), glass ionomer cement (n=27), silicone (n=9), or nothing (n=14). The mean (S.D.) follow-up time was 92 (26) months. Six months after operation, 27 (46%) of the plates with polymethylmethacrylate cement or glass ionomer cement were removed. During the same time period, four (28%) of the plates were removed in the group with no additional material and two (22%) in the group that had silicone. There was a significant difference in survival time of the metal between the group with silicone and the group with glass ionomer cement (p=0.014, log rank). Although silicone performed slightly better than the reconstruction plate on its own, we doubt whether any cement is necessary.

Occurrence of cervical lymph node metastasis of maxillary squamous cell carcinoma - A monocentric study of 171 patients.

INTRODUCTION: Fewer than 5% of oral squamous cell carcinomas (SCC) are presented in the maxilla. The absence of cervical lymph node metastasis (LNM) is one of the main positive prognostic factors. This single-centre study analysed the cervical lymph node metastasis behaviour in patients with oral SCC of the upper jaw and serves as a basis for a cervical lymph node treatment suggestion. MATERIAL AND METHODS: The retrospective study includes 171 patients with isolated SCC of the maxilla. In addition to tumour resection, 83% of the patients underwent a selective neck dissection (ND). The data of cervical metastasis, TNM-status, tumour grade, tumour location as well as nicotine and alcohol behaviour were statistically analysed. RESULTS: The average rate of cervical metastasis was 44% in total. Tumour stage significantly affected risk for cervical metastasis (T1 = 6%, T2 = 41%, T3 = 60% and T4 = 60%) (p < 0.01). Development of cervical LNM was seemingly influenced by male gender. DISCUSSION: This study postulates a high rate of cervical metastasis of maxillary SCC. Risk for metastasis is mainly determined by the tumour stage. Alcohol and nicotine abuse have a negative impact on cervical LNM. CONCLUSION: Reviewing recent literature underlined by the illustrated data, we put up for discussion the treatment of SCC of the maxilla as similar to therapy protocols for SCC of the oral cavity. This would include an ipsilateral ND even in low tumour stage and in T4 staged tumours on both sides. However, prospective multicentre studies are needed to verify and recommend these therapy assumptions.

Distinct site-specific oncoprotein overexpression in head and neck squamous cell carcinoma: a tissue microarray analysis.

BACKGROUND: Tissue microarray (TMA) analysis is a high-throughput approach that allows the screening of large tumor collectives for cytogenetic aberrrations. In this study, a TMA of a large collection of clinically well-defined primary squamous cell carcinomas of the head and neck (HNSCC) was used to determine the expression of several oncoproteins. MATERIALS AND METHODS: A TMA containing 547 primary HNSCC was used for the analysis of cyclinD1, c-myc, erbb1 and erbb2 expression by immunohistochemistry (IHC). RESULTS: CyclinD1 and c-myc were overexpressed at higher frequencies in primary pharyngeal and laryngeal carcinomas compared with primary oral carcinomas (p < 0.001 and p < 0.001), while erbb1 and erbb2 overexpression was associated with oral site (p < 0.001 and p = 0.04, respectively). Furthermore, cyclinD1 overexpression correlated with stage IV primary carcinomas (p = 0.04). CONCLUSION: HNSCC is a heterogenous group of tumors, which, depending on anatomic sites and clinical stage, shows variable expressions of the oncoproteins described. This indicates a specific pathogenic role of these oncoproteins in different subtypes of HNSCC and may have therapeutic implications.

Influence of marginal and segmental mandibular resection on the survival rate in patients with squamous cell carcinoma of the inferior parts of the oral cavity.

AIM: The aim of this retrospective study was to investigate whether radical (segmental resection) or conservative (marginal) resection of mandibular bone influenced patients, survival. PATIENTS AND METHODS: A series of 136 patients selected for partial mandibular resection for the treatment of squamous cell carcinomas of the lower oral cavity was evaluated retrospectively. Fifty-four patients underwent marginal and 82 cases segmental resection of the mandible. The mean follow-up periods were 91.1+/-30.1 months and 91.5+/-26.2 months, respectively. Data was extracted from the patient records and transferred into a database for statistical evaluation. Results Mean survival was 63.0+/-35.3 months for marginal and 53.1+/-32.3 months for segmental resection. The overall survival rate was analysed according to Kaplan-Meier and the test of significance (Log Rank) which yielded no statistically significant difference in the survival rate between both groups (p=0.1119). Numbers of recurrences, second primaries, metastases and/or postoperative complications were similar in both groups, i.e. no statistically significant differences were observed (ANOVA, Post-hoc Scheffé test). Conclusion In cases with an indication for bone resection, marginal resection may achieve satisfactory control and is as effective as segmental resection.

Oral health-related quality of life and depression/anxiety in long-term recurrence-free patients after treatment for advanced oral squamous cell cancer.

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.

The role of elective supraomohyoidal neck dissection in the treatment of early, node-negative oral squamous cell carcinoma (OSCC): a retrospective analysis of 122 cases.

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<0.001, respectively). Elective supraomohyoid neck dissection detects occult metastases in early, node-negative OSCC, and patients with early OSCC exhibiting occult metastases should be considered as high risk patients, warranting additional therapeutic regimes.

Changes in the mandibular and dento-alveolar structures by the use of tooth borne mandibular symphyseal distraction devices.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: Significant tilting of the anchorage teeth was observed (p<0.01). 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 (p<0.01). No significant change of the intercondylar distance was found pre- and postoperatively in the Wilcoxon test. CONCLUSION: 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.