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Purpose: Current staging methods for squamous cell carcinomas (SCC) of the oral cavity (OSCC) need to be improved to predict the risk of individual patients. Because hematogenous tumor cell dissemination is a key event in tumor progression, we assessed the prognostic significance of disseminated tumor cells (DTC) in bone marrow and circulating tumor cells (CTC) in peripheral blood from patients with OSCC.Experimental Design: From 110 patients with OSCC, tumors were surgically resected (R0) without neoadjuvant therapy. The CellSearch system was used to enumerate CTCs. Bone marrow was aspirated from the iliac crest, and mononuclear cells (MNC) were enriched by Ficoll density gradient centrifugation. To detect DTCs, MNCs were immunostained with the pan-keratin antibody A45-B/B3. Results were correlated with clinicopathologic parameters and clinical outcome such as recurrence and death during follow-up time (mean 916 days).Results: Ten of 80 patients (12.5%) harbored CTCs in peripheral blood, whereas in 18 of 90 patients (20.0%) DTCs in bone marrow could be detected. Surprisingly, in only 2 patients (1.8%) CTCs and DTCs were detected simultaneously. Significant correlations could be found for CTCs and tumor size (P = 0.04), nodal status and DTCs (P = 0.02), and distant metastasis with CTCs (P = 0.004) and DTCs (P = 0.005). Univariate and multivariate analyses revealed that CTCs and DTCs were significant and independent predictors of recurrence-free survival (P < 0.001).Conclusions: Both DTCs and CTCs are independent prognostic markers in patients with OSCC, predicting relapse with higher sensitivity at various disease stages than routine staging procedures. Bone marrow might be an interesting target organ for future therapeutic interventions. Clin Cancer Res; 20(2); 425–33. ©2013 AACR.

PDF file 404K, Supplementary Table 1: Detailed information for each CTC-positive patient regarding tumor size (T-stage), lymph node involvement (N-stage) and distant metastasis (M-stage) at diagnosis and number of CTCs/7.5 mL blood. Supplementary Table 2: Detailed information for each DTC-positive patient regarding tumor size (T-stage), lymph node involvement (N-stage) and distant metastasis (M-stage) at diagnosis and number of DTCs/2x106 mononuclear cells. Supplementary Figure 1: Gallery of CTC images generated with the CellSearch system from cases #1-10 equivalent to Patient ID in Supplementary Table 1. Supplementary Figure 2: Time to relapse for CTC-positive patients by adjuvant therapy (none, radiotherapy, radiochemotherapie, A left), A right: Time to relapse for CTC-negative patients by adjuvant therapy (none, radiotherapy, radiochemotherapie); B left: Time to relapse for DTC-positive patients by adjuvant therapy (none, radiotherapy, radiochemotherapie), right: Time to relapse for DTC-negative patients by adjuvant therapy (none, radiotherapy, radiochemotherapie) Supplementary Figure 3: Time to locoregional relapse for CTC-positive patients without metastatic disease at diagnosis (A); Time to locoregional relapse for DTC-positive patients without metastatic disease at diagnosis (B) Supplementary Figure 4: Gallery of detected DTCs from cases #1-18 equivalent to Patient ID in Supplementary Table 2

Background Prolyl hydroxylase 1 (PHD1) is a prognostic marker in several cancers. Aims and scopes This study was undertaken to elucidate the clinical relevance of PHD1 in colorectal cancer (CRC) prognosis. Materials and methods We compared PHD1 expression on a tissue microarray (TMA) containing samples from 1800 CRCs with corresponding clinicopathological tumor variables and patient survival. Results While PHD1 staining was always high in benign colorectal epithelium, high PHD1 staining was detectable in only 71.8% of CRCs. Low PHD1 staining was associated with advanced tumor stage (p = 0.0101) and shortened overall survival in CRC patients (p = 0.0011). In a multivariable analysis including tumor stage, histological type and PHD1 staining revealed tumor stage and histological type (p p = 0.0202) to be independent prognostic markers for CRC. Conclusions In our cohort, loss of PHD1 expression independently identified a subset of CRC patients with poor overall survival and might, thus, be a promising prognostic marker. PHD1 targeting may even allow for specific therapeutic approaches for these patients.

Radiofrequency microneedling (RFMN) treatment is the latest generation of fractional skin rejuvenation methods.To evaluate the efficacy, safety, tolerability and patient satisfaction of RFMN treatment for skin rejuvenation of the lower face and neck area.A prospective, intraindividual, controlled study. Subjects were treated with a fractional insulated RFMN system with 1 to 3 sessions at intervals of 4 to 12 weeks. Follow-up visits were scheduled on Day 90 and 180 posttreatment. Outcome was assessed by volume analysis of standardized 3-dimensional imaging, and validated clinical scales were rated by the physician, a blinded investigator, and patients.Thirty patients (mean age 55.5 years, Fitzpatrick skin type I-IV) were included. Mean submental volume difference was -4.72 cm3 (±10.07 cm3; range -26.65 cm3 to +16.01 cm3). Physician, blinded investigator, and subjects rated the clinical outcome as highly improved. Mean pain intensity was 5.61/10 on Numeric Rating Scale. Beside slight swelling and redness, no relevant downtime has been observed.Fractional RFMN treatment is a safe and effective technique for rejuvenation of the lower face, jawline, and neck region. Sufficient pain management should be provided. Data indicated low to no downtime and high patient satisfaction.

Background/aim Conventional in vitro assays measure the effect of drugs on total cells, while separating the effect to those on tumor and non-tumor cells is important for assessing drug specificity. Our aim was to evaluate the feasibility of separating the efficacy of vemurafenib on tumor and non-tumor cells in a mixed culture. Materials and methods Melanoma A2058 cells and CCD18Co non-tumor cells were mixed and treated with vemurafenib. DNA was subjected to digital PCR to determine the ratio of the mutant 1799A to the wild-type 1799T alleles and viabilities of total cells were subsequently calculated as percentages of tumor and non-tumor cells. Results The set-up proportion of tumor cells correlated well with the calculated one. The calculated viability of tumor cells decreased with increasing doses of vemurafenib while that of the non-tumor cells remained rather constant. Variability of digital PCR data was high. Conclusion Using the BRAF mutation 1799T>A to separate the response of tumor and non-tumor cells to a drug, such as vemurafenib, is feasible, supporting a foundation for a genetic in vitro tool for testing drug efficacy and specificity.

Aberrant expression of RNA-binding motif protein 3 (RBM3) has been suggested as a prognostic biomarker in several malignancies. This study was performed to analyse the prevalence and clinical significance of RBM3 immunostaining in non-small cell lung cancers (NSCLCs). Therefore, we took advantage of our tissue microarray (TMA) containing more than 600 NSCLC specimens. While nuclear RBM3 staining was always high in normal lung tissue, high RBM3 staining was only seen in 77.1% of 467 interpretable non-metastatic NSCLCs. Reduced RBM3 staining was significantly associated with advanced pathological tumor stage (pT) in NSCLCs (p = 0.0031). Subset analysis revealed that the association between reduced RBM3 staining and advanced pT stage was largely driven by the histological subgroup of lung adenocarcinoma (LUACs) (p = 0.0036). In addition, reduced RBM3 expression predicted shortened survival in LUAC patients (p = 0.0225). In summary, our study shows that loss of RBM3 expression predicts worse clinical outcome in LUAC patients.

Strong expression of survivin is associated with worse survival in many different tumours, and in cell culture, a correlation between radiation resistance and survivin expression can be seen. The potential of survivin expression as a prognostic/predictive marker or therapeutic target has not been examined in head and neck squamous cell carcinomas (HNSCC) yet. Retrospective study of 452 tissue samples and clinical data from patients with squamous cell carcinomas of the larynx/hypopharynx (LSCC), oral cavity (OSCC) and oropharynx (OPSCC) treated in the University Medical Centre Hamburg-Eppendorf between 2002 and 2006. The expression patterns were detected by tissue microarray technique and correlated with clinical parameters (sex, age, tumour location, TNM 7th edition, grading, recurrence-free and overall survival). 222 OSCC, 126 OPSCC and 105 LSCC tumours of 118 females and 335 males with a mean follow-up of 41.3 months were examined. Survivin expression correlates with pN, cM, pT and overall survival. The potential of survivin as a prognostic/predictive marker is very high. The findings have to be confirmed in a larger cohort of HNSCC esp. in those tumours treated primarily with radio/radiochemotherapy.

The heterotrimeric Sec61α translocon complex is topological located in the membrane of the endoplasmic reticulum (ER) and allows protein transport and calcium across the membrane. Recently, aberrant expression of Sec proteins was linked to carcinogenesis and prognosis of patients. Here, we analysed the role of Sec61α in esophageal cancer, and we analysed Sec61α staining on a tissue microarray containing more than 600 esophageal cancer specimens by immunohistochemistry. Sec61α staining was always strong in benign esophagus, but was only found in 5% of interpretable esophageal adenocarcinomas (EACs) and 14.5% of squamous cell carcinomas (ESCCs). Reduced Sec61α staining was not strongly linked to tumor phenotype in both subgroups of esophageal cancers and was unrelated to clinical outcome of patients (EACs: p = 0.8051 and ESCCs: p = 0.2751). Thus, Sec61α measurement has not an additional prognostic benefit for the patients.

Conventional in vitro assays measure the effect of drugs on total cells, while separating the effect to those on tumor and non-tumor cells is important for assessing drug specificity. Our aim was to evaluate the feasibility of separating the efficacy of vemurafenib on tumor and non-tumor cells in a mixed culture.Melanoma A2058 cells and CCD18Co non-tumor cells were mixed and treated with vemurafenib. DNA was subjected to digital PCR to determine the ratio of the mutant 1799A to the wild-type 1799T alleles and viabilities of total cells were subsequently calculated as percentages of tumor and non-tumor cells.The set-up proportion of tumor cells correlated well with the calculated one. The calculated viability of tumor cells decreased with increasing doses of vemurafenib while that of the non-tumor cells remained rather constant. Variability of digital PCR data was high.Using the BRAF mutation 1799TA to separate the response of tumor and non-tumor cells to a drug, such as vemurafenib, is feasible, supporting a foundation for a genetic in vitro tool for testing drug efficacy and specificity.

Background Abdominoplasty is one of the most commonly performed surgical procedures to reshape the body contour in patients who have undergone massive weight loss. Objectives This study was undertaken to assess the clinical outcome, complication rates, and risk factors for complications of patients undergoing abdominoplasty after massive weight loss. Setting University Medical Centre Hamburg-Eppendorf, Hamburg, Germany. Method Clinical outcome was retrospectively analyzed in 121 patients, who underwent abdominoplasty. The retrospective analysis included demographic data of patients, such as sex, age, body mass index (BMI), and pre-existing illnesses. Moreover, postoperative complications including seroma, hematoma, wound infection, and tissue necrosis were analyzed. Results In our study cohort, the median age was 43.7 years, the median weight was 94.7 kg, and the median BMI was 32.3 kg/m2. The majority of included patients were women (70.3%). Death occurred in none of the patients. Among individuals, wound infection occurred in 3.3%, tissue necrosis in 1.7%, seroma in 7.4%, and hematoma in 3.3% of patients during the postoperative course. Reoperations were necessary in 2 patients (1.7%) due to postoperative bleeding and tissue necrosis of the navel. Tissue necrosis was significantly more often seen in a subset individual with type 2 diabetes (P = .006). Moreover, the rate of reoperations was significantly higher in patients with pre-existing cardiovascular illnesses compared with cardiovascular healthy patients (P = .036). Multivariate analysis analyzing risk factors for postoperative complications, including sex, age, BMI, diabetes, pulmonary disease, and cardiovascular disease, revealed strong independent relevance for type 2 diabetes (P = .024). Conclusions We found that abdominoplasty is a safe operative procedure. In addition, the risk for complications is significantly increased in the subgroup of diabetic patients and patients with cardiovascular diseases.

Split-thickness skin grafting is a common procedure to treat different kinds of wounds. This systematic, multicentre, observational, cross-sectional study of adult patients with split-thickness skin graft (STSG) donor site wounds was conducted to evaluate quality of life (QoL) impairments caused by donor site wounds following split-thickness skin grafting. Therefore, 112 patients from 12 wound centres in Germany were examined based on patient and physician questionnaires as well as a physical examination of the donor site wound. Most indications for skin grafting were postsurgical treatment (n = 51; 42.5%) and chronic wounds (n = 47; 39.2%). European QoL visual analoque scale (EQ VAS) averaged 64.7 ± 23.3, European QoL 5 dimensions (EQ-5D) averaged 77.4 ± 30.0. Wound-QoL (range: 0-4) was rated 0.8 ± 0.8 post-surgery and 0.4 ± 0.6 at the time of survey (on average 21 weeks between the time points). Compared to averaged Wound-QoL scores of chronic wounds donor site-related QoL impairments in split-thickness skin-graft patients were less pronounced. There were significant differences in patient burden immediately after surgery compared to the time of the survey, with medium effect sizes. This supports the hypothesis that faster healing of the donor site wound leads to more favourable patient-reported outcomes.

Background Enhancer of zeste homolog 2 (EZH2), the catalytic subunit of the polycomb repressive complex 2, plays an important role in tumor development and progression by interacting with histone and non-histone proteins. EZH2 represents a putative therapeutic target and has been suggested as a prognostic marker in several cancer types. Material and methods This study investigates the prognostic relevance of immunohistochemical EZH2 expression in head and neck squamous cell carcinoma. Tissue microarray sections with 667 cancers of oral cavity, oro- and hypopharynx and larynx were analyzed for EZH2 expression. Results Nuclear EZH2 staining was recorded in 322 (81.8%) of 394 cases. Staining was weak in 33 (10.2%), moderate in 128 (39.6%), and strong in 103 (32.0%) cancers. The prevalence of EZH2 expression in tumors of the oral cavity and the orohypopharynx was higher as compared to cancers of the larynx (P = .0023). EZH2 expression was correlated to presence of lymph node metastasis (P = .0089) but was unrelated to histological grade, tumor stage, surgical margin, or distant metastasis. EZH2 expression had no impact on patient survival. Conclusion The high prevalence of EZH2 expression in head and neck squamous cell carcinoma stresses its capability as a therapeutic target.

Background βIII-tubulin (TUBB3) is an isotype of microtubules, which are involved in crucial cellular roles including maintenance of cell shape, intracellular transport, and mitosis. Overexpression of TUBB3 was found to be associated with poor prognosis and resistance to tubulin-binding drugs and in several solid tumors including head and neck squamous cell carcinomas (HNSCC). Considering the potential high importance of a prognostic biomarker in these cancers, the present study aimed to investigate the clinical relevance of immunohistochemical TUBB3 expression in HNSCC. Methods Tissue microarray (TMA) sections containing samples from 667 cancers of oral cavity, oro- and hypopharynx and larynx for which follow-up data were available were analyzed for TUBB3 expression by immunohistochemistry. Results Over 90% of our analyzed cancers showed unequivocal cytoplasmic TUBB3 expression. Staining was considered weak in 69 (15.5%), moderate in 149 (33.5%) and strong in 188 (42.2%) of cancers. The frequent TUBB3 overexpression showed no significant correlation with pathological grading, tumor stage, nodal status or surgical margin and had no impact on patient outcomes. Conclusion Despite of lacking prognostic utility in HNSCC, the remarkable high prevalence of TUBB3 expression in HNSCC emphasizes its putative relevance as a target for future drugs targeting TUBB3. This article is protected by copyright. All rights reserved.

Purpose Microvascular free tissue transfer allows major ablative defects following oncologic surgical and traumatic reasons to be reliably reconstructed in the head and neck region. A retrospective analysis of the microvascular flap procedures which were performed within one year in a high volume training centre was performed. Patients and methods The microvascular free flap procedures of the year 2011 were reviewed and followed up until the 31st December 2012. The type and indication of the reconstructive procedure, operation time, operating team, experience and level of training of the surgeons involved, postoperative IMC (intermediate care unit) and/or ICU (intensive care unit) time, inpatient time, flap revisions, further postoperative complications, preoperative and postoperative radiation of the patients, the placement of dental implants were studied. Results From 1st of January 2011 to 31st of December, 2011, the data of 101 patients with 103 microvascular free flap procedures were analysed of which 72% (84 flaps) were harvested by residents. The patients ranged in age from 14 to 89 years (mean age 59 years, 71 males and 40 females). The mean operation time was 591 min with the longest operation times for scapular flaps (744 min) and the shortest operation times for ALT flaps (455 min). Mean inpatient time was 34.2 days with a minimal time for the fibular flaps of 27.2 days and a maximum of 45.7 days for the latissimus dorsi flaps. 24 flaps (23.3%) in total had to be revised with bleeding being the main cause of immediate revisions (41.7% of all revisions). 5 flaps (4.85% of all flaps) were lost despite a revision procedure meaning a successful revision rate in 79.2% of all revisions. Conclusion Microvascular reconstruction procedures are safe and should be considered as standard procedures for reconstruction of large defects especially in high volume training centres. Intensive flap monitoring and early revisions maximize the flap outcome.

The widely used panoramic radiography as a special kind of tomography underlies intrinsic procedural restrictions such as poor definition, inconsistent magnification, geometric distortion and spatial depositioning of objects situated outside the focal trough. This results in a non-anatomic display of the radiographed anatomic structures. Individual mandibular angle and width of the jaws, adjustment of the focal trough, jaw incongruence as well as patient positioning increase the inconsistency in display of the radiographed objects. This study precisely evaluated the quantitative impact of object malpositioning on the display in panoramic radiography. A special dental implant model was highly accurate three dimensionally malpositioned and panoramic radiographs were taken. Automated image analysis was performed to exclude subjective assessment error. Precise and retraceable object deposition of up to 5 mm or 5° resulted in relevant deposition of objects and significant changes in object size and inter-object distances in the panoramic image. Unidirectional malpositioning lead to multiple errors in display. The extent of malpositioning-related display errors additionally to the known physicotechnical insufficiencies of the panoramic radiography demonstrates its limitations in precisely interpreting spatial relationships. Measurements within the panoramic radiography must not claim reliability. For a single object securely positioned in the focal trough and perpendicular to the central X-ray beam, measurements may be trustworthy on clinical scale. Once sterical relationships to other structures are evaluated, reliability must be questioned.

The prognosis of head and neck squamous cell carcinoma (HNSCC) patients remains poor. The identification of high-risk subgroups is needed for the development of custom-tailored therapies. The expression of cancer-testis antigens (CTAs) has been linked to a worse prognosis in other cancer types; however, their prognostic value in HNSCC is unclear because only few patients have been examined and data on CTA protein expression are sparse. A tissue microarray consisting of tumor samples from 453 HNSCC patients was evaluated for the expression of CTA proteins using immunohistochemistry. Frequency of expression and the subcellular expression pattern (nuclear, cytoplasmic, or both) was recorded. Protein expression of melanoma antigen (MAGE)-A family CTA, MAGE-C family CTA and NY-ESO-1 was found in approximately 30, 7 and 4% of tumors, respectively. The subcellular expression pattern in particular had a marked impact on the patients' prognosis. Median overall survival (OS) of patients with (i) simultaneous cytoplasmic and nuclear expression compared to (ii) either cytoplasmic or nuclear expression and (iii) negative patients was 23.0 versus 109.0 versus 102.5 months, for pan-MAGE (p

To develop a new radiography-based score to assess the potential of bacteria to cause odontogenic infections derived from the occurrence of bacteria at small or large radiographical lesions.The patients analyzed were a sub-population from a large randomized clinical trial comparing moxifloxacin and clindamycin in the treatment of inflammatory infiltrates and odontogenic abscesses. Routine radiographs were used to analyze the area of the periapical radiolucent lesions. Lesions were stratified by their radiographically measured area as large (9 mm(2)) or small (≤9 mm(2)). A risk ratio was calculated for each species from the frequency of their occurrence in large vs in small lesions.Fifty-one patients, 19 with abscesses and 32 with infiltrates, were evaluated. Overall, the radiographical lesion areas ranged from 0.4-46.2 mm(2) (median = 9 mm(2)). An increased risk (risk ratio1) to occur at large abscess lesions was observed for Prevotella (P.) oralis, P. buccae, P. oris, P. intermedia, Fusobacterium nucleatum and Streptococcus (Strep.) anginosus group. An increased risk to occur at large infiltrate lesions was found for Strep. salivarius, Strep. parasanguis, Strep. anginosus group, Capnocytophaga spp., Neisseria (N.) sicca, Neisseria spp., Staphylococcus (Staph.) aureus, P. intermedia, P. buccae, Prevotella spp. and P. melaninogenica.The radiography-based score suggests that certain Prevotella spp., F. nucleatum and Strep. anginosus groups play a crucial role in the pathogenesis of odontogenic abscesses, and that various streptococci, Neisseria spp., Capnocytophaga spp., Staph. aureus and Prevotella spp. are involved in the pathogenesis of odontogenic infiltrates.

Purpose: Current staging methods for squamous cell carcinomas (SCC) of the oral cavity (OSCC) need to be improved to predict the risk of individual patients. Because hematogenous tumor cell dissemination is a key event in tumor progression, we assessed the prognostic significance of disseminated tumor cells (DTC) in bone marrow and circulating tumor cells (CTC) in peripheral blood from patients with OSCC. Experimental Design: From 110 patients with OSCC, tumors were surgically resected (R0) without neoadjuvant therapy. The CellSearch system was used to enumerate CTCs. Bone marrow was aspirated from the iliac crest, and mononuclear cells (MNC) were enriched by Ficoll density gradient centrifugation. To detect DTCs, MNCs were immunostained with the pan-keratin antibody A45-B/B3. Results were correlated with clinicopathologic parameters and clinical outcome such as recurrence and death during follow-up time (mean 916 days). Results: Ten of 80 patients (12.5%) harbored CTCs in peripheral blood, whereas in 18 of 90 patients (20.0%) DTCs in bone marrow could be detected. Surprisingly, in only 2 patients (1.8%) CTCs and DTCs were detected simultaneously. Significant correlations could be found for CTCs and tumor size (P = 0.04), nodal status and DTCs (P = 0.02), and distant metastasis with CTCs (P = 0.004) and DTCs (P = 0.005). Univariate and multivariate analyses revealed that CTCs and DTCs were significant and independent predictors of recurrence-free survival (P < 0.001). Conclusions: Both DTCs and CTCs are independent prognostic markers in patients with OSCC, predicting relapse with higher sensitivity at various disease stages than routine staging procedures. Bone marrow might be an interesting target organ for future therapeutic interventions. Clin Cancer Res; 20(2); 425–33. ©2013 AACR.

Numb chin syndrome (NCS) describes a sensory neuropathy characterized by numbness in the distribution of the terminal branch of the mandibular division of the trigeminal nerve. Benign as well as malignant diseases are known to cause NCS. This is often misdiagnosed, and in some cases the symptom may lead to a late detection of malignancy. Reports of 10 cases in which NCS was the presenting and isolated symptom, caused by extracranial malignancies, drugs, or dental/surgical interventions, are presented. This article outlines the symptoms and the diagnostic approaches taken, provides a short review of the etiology and pathogenesis, and proposes diagnostic criteria and treatment of NCS. Both medical practitioners and dentists need to be aware of the relationship between malignancies and paresthesia of the chin or complete loss of sensation in partial segments of the jaw. In addition, dentists should be aware of the diagnostic limitations of an orthopantomogram to detect underlying diseases beyond localized dental disorders.

Epidermal growth factor receptor (EGFR) expression is altered in several malignancies, including oral squamous cell carcinoma. A CA-repeat polymorphism in intron-1 (CA-SSR-1) of the EGFR gene is reported to influence EGFR expression and is associated with features of various solid tumors and outcomes of cancer patients. In the present study we evaluated the influence of length and zygosity of CA-SSR-1 on the survival of patients with oral squamous cell carcinoma. The length and zygosity of CA-SSR-1 was obtained through microsatellite analysis in 91 patients with oral cancer, who were treated in the Department of Oral and Maxillofacial Surgery of the University Medical Centre Hamburg Eppendorf, Germany, during the years 1998-2008. Follow up was conducted until 2016. Outcome measures were age, gender, tumor stage, occurrence of metastases, and date of recurrence or death. Statistical analysis was conducted using the chi-square test and the log-rank test. Neither length nor zygosity of the CA-SSR-1 in patients with oral squamous cell carcinoma was significantly correlated with sex, age, tumor size, tumor localization, lymph node involvement, metastasis status, disease-free survival, or overall survival. Length and zygosity of the CA-SSR-1 polymorphism in EGFR is not able to serve as a prognostic biomarker in White European patients with oral squamous cell carcinoma.

Objectives Functional inactivation of p16 is an early and frequent event in the carcinogenesis of tumours of the head and neck region. However, the prognostic relevance of p16 protein expression for these tumours has been controversial. This study aims to examine immunohistochemical expression of p16 and HP virus in a large number of oral carcinomas, and possible correlation with clinical features of the tumours and survival of the patients. Methods Two tissue microarrays composed of 222 oral carcinomas and 427 squamous cell carcinomas of the head and neck region were used for this study. Sections were stained immunohistochemically (anti-p16), and PCR analysis (HPV status) was carried out. Correlation of p16 expression/HPV status with features of tumours and with survival of the patients was analysed by means of Chi-squared test and using Kaplan–Meier analysis, respectively. Results p16 expression was found immunohistochemically in 74% of tumours, but was not significantly correlated with features of the tumours, but recurrence-free survival of the patients (P = 0.009) if located predominantly nuclear. On the other hand neither intensity of p16 expression (P = 0.41) nor HPV status (P = 0.82) had any effect on these two aspects. Conclusion Immunohistochemical expression of p16 alone provides a limited tool for diagnosis and prognosis of carcinomas of the head and neck region. Immunohistochemical analysis of p16 depending on its intracellular location might serve as a surrogate marker for HPV infection.

Gene products, which show a significant association to cell proliferation and cell cycle control, are of high scientific interest, because genes as well as gene products could be possible targets for a specific therapeutic approach and eventually be prognostic markers. Cyclin D1 expression and amplification as well as the Ki-67 expression status were examined in a two tissue microarray analysis for head and neck squamous cell carcinoma (HNSCC) including 546 patients. A tumour site-specific analysis and a survival analysis of 222 oral squamous cell carcinoma (OSCC) patients were performed. Cyclin D1 amplification status was examined with fluorescence in situ hybridisation analysis, while cyclin D1 expression and Ki-67 expression status were examined with IHC. Amplification of the CCND1 gene and immunohistochemical expression of cyclin D1 and Ki-67 were examined in 546 tumours of the head and neck region in two tissue microarrays. CCND1 amplification was significantly more frequent in pharyngeal carcinomas (63 %) than in laryngeal (37 %) and oral (25 %) carcinomas. Among the 222 cases of OSCCs, both CCND1 amplification and cyclin D1 expression were significantly associated with overall survival of the patients (p = 0.0127 and p = 0.0004, respectively). Ki-67 expression was significantly associated with cyclin D1 expression and with amplification of the CCND1 gene (p = 0.0002 and p = 0.0015, respectively) but not with patient overall survival. Our results suggest the prognostic value of CCND1 amplification and cyclin D1 expression for patients with OSCC and highlight the genetic differences in HNSCC of different subanatomic localisation. Cyclin D1 expression and CCND1 amplification seem to have a prognostic value for OSCC. Further studies of HNSCC should always consider subanatomic genetic differences.

This study evaluates a novel adhesive fixation technique to affix cortical bone fragments to osteosynthesis plates using common PMMA cement. This technique utilizes a new amphiphilic bone bonding agent adhering with both hydrophilic bone and hydrophobic PMMA cement. After in vitro biomechanical testing of the bonding strength with explanted bovine and rabbit calvarian bone samples, osteosynthesis plates with screw holes of 1.3 and 1.5 mm were placed on the cranial bone of New Zealand white rabbits and the bond strength of these plates was determined through tension tests. In vitro bond strengths of 19.8-26.5 MPa were obtained. Control samples, prepared without a bone bonding agent, exhibited bone bonding strengths

CD151 is a plasma membrane protein belonging to the tetraspanin family. CD151 represents a putative therapeutic target and has been suggested as a prognostic marker in several cancer types. The present study aims to investigate the prognostic relevance of immunohistochemical CD151 expression in head and neck squamous cell carcinoma (HNSCC). Tissue microarray (TMA) sections containing samples from 667 cancers of oral cavity, oro- and hypopharynx and larynx, for which follow-up data were available, were analyzed for CD151 expression by immunohistochemistry. Membranous CD151 immunostaining was recorded in 269 (60.3 %) of 446 analyzable cases. Staining was considered weak in 129 (28.9 %), moderate in 98 (22.0 %), and strong in 42 (9.4 %) of cancers. CD151 expression was unrelated to histological grade, tumor stage, nodal status, or surgical margin. There was a tendency towards a somewhat lower prevalence of CD151 expression in tumors of the oral cavity (52.9 % positive) as compared to cancers of the oro-hypopharynx (62.1 %) and larynx (63.3 %; p = 0.0100). CD151 expression had no impact on patient survival. In summary, immunohistochemical analysis of CD151 lacks prognostic utility in HNSCC. The high prevalence of CD151 expression in HNSCC emphasizes its putative relevance as a therapeutic target for further development of anti-CD151 drugs.

For application of stem cells and progenitor cells in regenerative medicine, scaffolds for carrying the cells play a key role. One promising biomaterial for scaffold generation is silk because of its mechanical strength, good cytocompatibility and low immunogenicity. Furthermore, bioengineering of silk proteins enable co-expression of various growth, differentiation and angiogenic factors on silk fibers, which may promote cell growth, differentiation and angiogenesis. This study aimed to test cytocompatibility and growth/differentiation of pre-adipose cells on scaffolds with and without expressed growth factors fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF).Disk-form scaffolds of 15×3 mm (diameter × thickness) were manufactured in two different densities using silk with and without expressed growth factors FGF-2 or VEGF. Pre-adipose cells were prepared from fatty tissues of patients undergoing operation. Cells (1.6×10(6)) were seeded onto each of the silk-scaffold disks, that were placed into wells of 12-well culturing plates. Adipose-differentiation was induced using differentiation medium containing DMEM/F-12, insulin, pantothenate, biotin, triiodothyronine (T3), transferrin, dexamethasone, isobuthylmethylxanthine and rosiglitazone. Cells on the scaffolds were visualized using a confocal microscope. Viability and adiponectin were measured on days 0, 7 and 14. Expression of adipose-differentiation markers was assessed by means of real-time polymerase chain reaction (RT-PCR).Pre-adipose cells attached well onto the silk fibers. The highest initial viability was measured on the low-density scaffolds with expressed VEGF. Adipose-differentiation was evident in visible oil droplets and significantly increased adiponectin protein levels were seen in ELISA. Furthermore, increased expression of adipose-differentiation genes were measured in RT-PCR. Adipose-differentiation was more profound in cells on high-density scaffolds. In concordance, viability of cells on high-density scaffolds did not increase, while that of cells on low-density scaffolds doubled over the 14-day experimental period. Slightly enhanced adipose-differentiation was observed in cells on scaffolds with expressed FGF-2 or VEGF.Silk scaffolds exhibit excellent cytocompatibility for human pre-adipose cells and have application potential in tissue engineering and regenerative medicine. VEGF and FGF-2 expressed on silk fibers could have a potential positive effect on pre-adipose cells, while the effect of VEGF should be further addressed in vivo.

Cluster headache (CH) is a debilitating, severe form of headache. A novel non-systemic therapy has been developed that produces therapeutic electrical stimulation to the sphenopalatine ganglion (SPG). A transoral surgical technique for inserting the Pulsante SPG Microstimulator into the pterygopalatine fossa (PPF) is presented herein. Technical aspects include detailed descriptions of the preoperative planning using computed tomography or cone beam computed tomography scans for presurgical digital microstimulator insertion into the patient specific anatomy and intraoperative verification of microstimulator placement. Surgical aspects include techniques to insert the microstimulator into the proper midface location atraumatically. During the Pathway CH-1 and Pathway R-1 studies, 99 CH patients received an SPG microstimulator. Ninety-six had a microstimulator placed within the PPF during their initial procedure. Perioperative surgical sequelae included sensory disturbances, pain, and swelling. Follow-up procedures included placement of a second microstimulator on the opposite side (n = 2), adjustment of the microstimulator lead location (n = 13), re-placement after initial unsuccessful placement (n = 1), and removal (n = 5). This SPG microstimulator insertion procedure has sequelae comparable to other oral cavity procedures including tooth extractions, sinus surgery, and dental implant placement. Twenty-five of 29 subjects (86%) completing a self-assessment questionnaire indicated that the surgical effects were tolerable and 90% would make the same decision again.

Department of Radiation-Oncology,University Medical Center Hamburg-Eppendorf, Hamburg, GermanyBACKGROUND: Insulin-like growth factor II mRNA-binding protein 3 (IMP3) was found overexpressed invarious cancer types suggesting its possible role in carci-nogenesis. Analysis of IMP3 expression in head and necksquamous cell carcinomas (HNSCC) is rare so that weevaluated it using tissue microarray method.METHOD: Immunohistochemical analysis of IMP3 wasperformed on samples from over 400 patients. Theexpression was measured semiquantitative, subsequentlydivided into four categories (negative, weak, medium, orstrong) and correlated with several available clinico-pathologic parameters.RESULTS: For HNSCC, positive IMP3 expression wasobserved in patients with all tumor stages (pT1–4) andnodal stages (pN0–3), showing also significant statisti-cal correlation (P = 0.023 and P = 0.0013, respectively).No further correlations were found. Separate analysisaccording to tumor localization (oral cavity, oropharyn-geal, and laryngeal) showed a significant correlation ofpositive IMP3 expression and overall survival (P = 0.038)only in patients with tumors of the oral cavity. Multivar-iate analysis showed IMP3 as an independent predictivemarker for oral squamous cell carcinomas (OSCC).CONCLUSION: Insulin-like growth factor II mRNA-binding protein 3 (IMP3) expression might be used as anindependent prognostic factor in the subgroup of OSCC.J Oral Pathol Med (2013) 42: 125–132Keywords: biomarker; head and neck squamous cell carcinoma;insulin-like growth factor II mRNA-binding protein 3; oralsquamous cell carcinoma

The buccal fat pad (BFP) as pedicled graft was originally used in reconstructing medium sized intraoral defects. Promising results concerning the use of BFP in cleft palate surgery have been published recently. The aim of this article is to report on the use of BFP as a pedicled graft in cleft palate surgery and to discuss promising results for this reconstructive surgical concept. A retrospective evaluation of 24 patients who had BFP pedicled flaps used for the prevention and repair of Type III (Pittsburgh Fistula Classification) cleft palate fistulas, to obstruct the retromolar space of Ernst and in case of wide clefts, from 2005 to 2010, was conducted. In all cleft palate patients, the recipient area fully epithelialized within 4 weeks or less. No recurrence was seen and the donor site healed well without aesthetic or significant functional impairment. This series confirms the excellent and predictable healing of BFP intraorally and the minimal morbidity associated with the use of such grafts. The results of this study allow the authors to recommend that the BFP pedicled flap is considered as a reliable alternative procedure to expand the therapeutic options. The BFP graft provides an advantage in reconstructive cleft palate surgery.

Purpose This study aimed to evaluate the use of intraoperative cone-beam computed tomography (CBCT) in monitoring the results of repositioning and osteosynthesis of condylar process and head (capitulum) fractures of the mandible to see if CBCT is beneficial for these patients. Patients and methods Sixty patients (22 females and 38 males, age range 16–17 years, average 36.5 years) with condylar process and head fractures according to the classification of Spiessl and Schroll were treated during the study period. Thirty-four of the 60 patients received a CBCT scan immediately after surgical treatment under aseptic conditions. Results In all 34 cases, intraoperative CBCT provided high-quality imaging of the condylar process in all three planes. In four patients (11.8%), unsatisfactory reposition or unexpected complications were detected which could immediately be corrected with a surgical revision. Conclusion Intraoperative use of CBCT enables optimization of the surgical outcome for fractures of the condylar process and head of the mandible, reduces postoperative complications, and spares patients from repeated intervention. In addition, intraoperative CBCT enables safer treatment with minimally invasive approaches.

Resorbable alloplastic materials are used in many surgical applications. This retrospective study evaluated the clinical outcome after reconstruction of traumatic orbital floor defects using a polyglactin 910/PDS implant (Ethisorb™).Seventy patients with isolated blowout fractures of the orbital floor resulting in defect sizes of up to 2.5 cm(2) were included in this study. All patients were clinically examined 5 days after surgery at the time of suture removal (T1) and 18 months postoperatively (T2). Diplopia was graded as significant diplopia or diplopia in extreme gaze.At T1, diplopia was observed in 9% of the patients, swelling of the periorbital region in 6%, and enophthalmus in none of the patients. No persistent complications were observed at T2.Reconstructive surgery of the orbit is one of the most demanding challenges in maxillofacial surgery. For traumatic defects of the orbital floor, reconstruction using a polyglactin 910/PDS implant (Ethisorb(™)) seems to be a reliable method for the repair of small-to-moderate defects.

Malignant tumors in the oral cavity are relatively rare. About 5% of all malignant growths in the body are localized in the oral cavity. The vast majority of oral malignancies are primary tumors with squamous cell carcinoma being the most frequent and sarcomas occurring very seldom. Secondary tumors caused by hematogenous spread arising from a tumor localized elsewhere in the body are extremely rare. About 1% of all oral cancers are metastases to the jawbones and the surrounding soft tissues. Metastases to the jaws are mainly caused by malignant tumors of the breast, lung, kidney, bone, and colon. They occur in the late state of the disease and are regularly detected by staging examinations including scintigraphy. Even more rare are metastases into odontogenic cysts. Odontogenic cysts include dentigerous cysts, periapical or radicular cysts, and the keratocysts-nowadays declared as keratocystic odontogenic tumor. The incidence of odontogenic cysts is about 10% to 15% of all oral biopsies and therefore general dentists are frequently faced with these types of lesions. The aim of this study was to review the literature regarding metastasis into odontogenic cysts and to further highlight this rare entity with the help of a clinical case.

Summary Purpose The results of primary bone grafting in terms of initial cleft width, existence or absence of a lateral incisor and scar formation in the donor area are compared. Methods After primary osteoplasty with calvarian bone at an average age of 24 months (4–56 months) radiographic assessment was carried out in 31 patients with 40 alveolar clefts. The bone formation in the grafted area was assessed using dental radiographs taken at 66 months on average (13–114 months) after primary bone grafting. According to the Abyholm classification patients were assigned to 4 groups (indices I–IV) with indices I and II being rated as a success. Results We observed success (indices I and II) in 76% and poor results (index IV) in 14%. The causes for the poor results were an alveolar cleft width of 11–12 mm in three cases, an extraction of a decayed deciduous tooth 17 months after bone grafting in one case and a traumatic transplant loss in another case. The non-existence of a lateral incisor and a broad cleft are related to poor results. Conclusion Based on the results presented, primary bone grafting using calvarial bone seems to be a promising alternative in bridging narrow alveolar defects. This method allows early intervention at an age in which children do not recognize themselves as cleft patients. The preservation of the deciduous teeth is equally important regarding their functional stimulus for bone development.

Object The aim of our study was to demonstrate the image quality of the new device using human cadavers, extending the horizon of available imaging modalities in forensic medicine. Materials and methods Six human cadavers were examined, revealing C-arm data sets of the head, neck thorax, abdomen and pelvis. High-resolution mode was performed with 500 fluoroscopy shots during a 190° orbital movement with a constant tube voltage of 100 kV and a current of 4.6 mA. Based on these data sets subsequent three-dimensional reconstructions were generated. Results Reconstructed data sets revealed high-resolution images of all skeletal structures in a near-CT quality. The same image quality was available in all reconstruction planes. Artefacts caused by restorative dental materials are less accentuated in CBCT data sets. The system configuration was not powerful enough to generate sufficient images of intracranial structures. Conclusion After the here-demonstrated encouraging preliminary results, the forensic indications that would be suitable for imaging with a 3D C-arm have to be defined. Promising seems the visualization local limited region of interest as the cervical spine or the facial skeleton.

Background: Transcriptional activity of the heme oxygenase-1 gene (HMOX-1) is modulated by a GTn-repeat promoter polymorphism. The long GTn-repeat allele has been previously reported to be associated with increased risk of oral squamous cell carcinoma (OSCC) in male areca chewer and short GTn-repeat allele has been proposed to have protective properties in OSCC patients. The aim of the present study was to correlate the GTn-repeat genotypes with clinicopathological characteristics along with clinical outcome of non-areca chewer OSCC patients. Methods: DNA of 99 patients that underwent complete surgical resection of OSCC was analyzed for GTn-repeat polymorphism in the HMOX-1 promoter by polymerase chain reaction, capillary electrophoresis and DNA sequencing. Results: Seven SS (7.1%), 51 SL (51.5%) and 41 LL (41.4%) genotypes were found. In a total of 14 (14.1%) patients, tumor recurrence (TR) was observed. There was no TR in the SS allele carriers. In SL carriers three and in LL 11 TR occurred (P = 0.009, chi-squared test). Mean relapse-free survival was 109.2 months in SL allele carriers compared with 72.3 months in LL allele carriers (P = 0.01, log-rank test). Multivariate Cox regression modeling identified GTn-repeat genotype as an independent prognostic factor (P = 0.03; relative risk (RR) 4.1; 95% CI 1.1–14.6). Conclusion: Presence of S allele was associated with a lower TR rate and better relapse-free survival in OSCC patients. HMOX-1 promoter polymorphism might be considered as a potential prognostic marker in OSCC patients.

Purpose This study investigated 3-dimensional (3D) imaging with intraoperative cone beam computed tomography (CBCT) in major mandibular reconstruction procedures. Patients and Methods The study group was comprised of 125 patients (83 males, 42 females) admitted for surgical treatment of the mandible. The patients ranged in age from 3 months to 91 years (average age, 40.72 ± 22.843 years). Surgical procedures of the mandible were subdivided into repair of body fractures (17 patients), angle fractures (21 patients), condylar fractures (14 patients), and multiple fractures (30 patient). In addition, the study group included 21 patients undergoing orthognatic surgery and 22 undergoing reconstructive surgery on the mandible. Intraoperatively, 3D images were generated with a mobile CBCT scanner (Arcadis Orbic 3D; Siemens Medical Solutions, Erlangen, Germany). Results During open reduction of mandibular fractures, not all fracture sites can be readily exposed for direct visual control. For example, the lingual cortical bone of the mandible is difficult to assess intraoperatively. This structure and others can be effectively visualized using the 3D mode of CBCT. Furthermore, screw placement can be evaluated, specifically in insertions near the alveolar nerve. The intraoperative acquisition of the data sets is uncomplicated, and the image quality is sufficient to allow evaluation of the postoperative result in all cases. Conclusion Intraoperative CBCT has proven to be a reliable imaging technique for providing visual control during major mandibular procedures.

Short tandem repeat (STR) polymorphisms in exon 4 of esophageal cancer related gene 2 (ECRG2) are a prognostic marker for squamous cell carcinoma (SCC) of the esophagus. The aim of the present study was to correlate these STRs with clinical outcome of the similar tumor type oral squamous cell carcinoma (OSCC). DNA of 81 patients that underwent complete surgical resection of OSCC was analyzed for STRs TCA3/TCA3, TCA3/TCA4 and TCA4/TCA4 in exon 4 of ECRG2 by PCR, capillary electrophoresis and DNA sequencing. ECRG2 STR TCA3/TCA3 were found in 45 (56%), TCA3/TCA4 in 33 (41%) and TCA4/TCA4 in 3 (3%) patients. TCA3/TCA3 was significantly associated with reduced relapse-free survival of OSCC, compared with TCA3/TCA4 and TCA4/TCA4 genotypes (P

The aim of this study was to test a previously described training tool for ultrasound for use as a first-line imaging modality. Navigated sonography was performed in 10 patients with midfacial fractures diagnosed using computed tomography (CT). One examiner ranked his sonographic findings regarding the presence of a fracture on six predefined anatomic landmarks on a scale from 1 to 5. These results were correlated with CT findings by displaying fused images. In all but three patients fractures were correctly identified using sonography. In the remaining three patients the examiner was unable to determine whether a fracture was present or not. Normally, these patients would have been subjected to conventional radiographs. Ultrasound proved to be a reliable first-line imaging modality for the investigation of suspected midfacial fractures in daily clinical practice, resulting in decreased radiation exposure since conventional radiographs are omitted. According to this algorithm, patients with sonographically confirmed midfacial fractures are examined for surgical planning using cone-beam CT.

The aim of this study was to retrospectively analyze surgical outcome and complications of 540 free flap procedures performed at the Department of Oral and Maxillofacial Surgery of the University Medical Center Hamburg-Eppendorf during 1987-2005. A total of 532 patients were reconstructed with 540 flaps: 32% were latissimus dorsi flaps, 23% were radial forearm flaps, 21% were iliac crest flaps, 10% were fibula flaps, 6% were jejunal flaps, and 8% were other flaps. Thrombosis of one of the vessels and hematoma were the most frequent causes of failure in microvascular free tissue transfer. A total free flap failure occurred in 34 (6.2%) and a partial flap failure in 42 (7.7%) patients. The most reliable flap in regard to survival was the radial forearm flap. The present study confirms that free flaps are extremely reliable in achieving successful reconstruction of the head and neck.

Introduction The objective of this study was to determine whether postoperative control of the neurostimulator placement within the pterygopalatine fossa (PPF) by means of 3-dimensional (3D) cone beam computed tomography (CBCT) was of therapeutic relevance compared to intraoperative CBCT imaging alone. Material and methods Immediately after implantation of the sphenopalatine ganglion (SPG) neurostimulator, intraoperative CBCT datasets were generated in order to visualize the position of the probe within the PPF. Postoperatively, all patients received a CBCT for comparison with intraoperatively acquired radiographs. Results Twenty-four patients with cluster headache (CH) received an SPG neurostimulator. In 4 patients, postoperative CBCT images detected misplacement not found in intraoperative CBCT. In 3 cases, electrode tips were misplaced into the maxillary sinus and in 1 case into the apex of the PPF superior to the suspected location of the SPG. Immediate revision with successful repositioning within 3 days was done in 2 patients and a deferred reimplantation in 1 patient within 6 months. One patient declined revision. Conclusion We were able to demonstrate the clinical value of postoperative dental CBCT imaging with a wide region of interest (ROI) due to a superior image quality compared with that achieved with intraoperative medical CBCT. Although intraoperative 3D CBCT imaging of electrode placement is helpful in the acute surgical setting, resolution is, at present, too low to safely exclude misplacement, especially in the maxillary sinus. High-resolution postoperative dental CBCT allows rapid detection and revision of electrode misplacement, thereby avoiding readmission and recurrent tissue trauma.

Purpose Her2 (ErbB2) transforms cells when overexpressed and is an important therapeutic target in breast cancer. Contrary to breast cancer, studies on Her2 overexpression and gene amplification in squamous cell carcinomas of the head and neck region described largely different results. This study was undertaken to learn more on the prevalence and clinical significance of HER2 amplification and overexpression in squamous cell carcinomas of the head and neck. Materials and methods Her2 expression and gene amplification was analyzed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) on two tissue microarrays composed of 427 squamous cell carcinomas of the head and neck region and 222 oral squamous cell carcinomas. Results were compared with clinicopathological features. Results Her2 expression and gene amplification was rarely detectable in squamous cell carcinomas of the head and neck region and unrelated to tumor phenotype or survival of the patients with oral squamous carcinoma. Discussion Our results demonstrate that Her2 protein and gene amplification was only detectable in a small subset of squamous cell carcinomas of the head and neck region as well as oral squamous cell carcinomas. However, it can be speculated that those few patients with Her2 overexpressing and gene amplificated tumors may possibly benefit from an anti-Her2 therapy.

Cyclin D1 gene (CCND1) has a G to A polymorphism at the splice donor site of exon 4, position 870. The A allele codes for a truncated variant, cyclin D1b, which may have higher transforming activity. Data regarding the predictive and prognostic value of the CCND1 G870A polymorphism in tumors are controversial. We aimed to examine this polymorphism in patients with oral carcinoma.Genotyping of CCND1 G870A was determined by means of direct sequencing in 83 patients with oral carcinomas and in 102 healthy controls. Association with clinical outcomes was evaluated statistically.We failed to find any significant association of CCND1 G870A with risk of oral carcinomas in this German population, with clinical and pathological features of the tumours or with overall survival of the patients.Our results suggest that CCND1 G870A has no, or only very limited, predictive and prognostic value for oral carcinoma.

The prognosis of head and neck squamous cell carcinoma (HNSCC) patients remains poor. The identification of high-risk subgroups is needed for the development of custom-tailored therapies. The expression of cancer-testis antigens (CTAs) has been linked to a worse prognosis in other cancer types; however, their prognostic value in HNSCC is unclear because only few patients have been examined and data on CTA protein expression are sparse. A tissue microarray consisting of tumor samples from 453 HNSCC patients was evaluated for the expression of CTA proteins using immunohistochemistry. Frequency of expression and the subcellular expression pattern (nuclear, cytoplasmic, or both) was recorded. Protein expression of melanoma antigen (MAGE)-A family CTA, MAGE-C family CTA and NY-ESO-1 was found in approximately 30, 7 and 4% of tumors, respectively. The subcellular expression pattern in particular had a marked impact on the patients' prognosis. Median overall survival (OS) of patients with (i) simultaneous cytoplasmic and nuclear expression compared to (ii) either cytoplasmic or nuclear expression and (iii) negative patients was 23.0 versus 109.0 versus 102.5 months, for pan-MAGE (p 0.0001), 46.6 versus 50.0 versus 109.0 for MAGE-A3/A4 (p = 0.0074) and 13.3 versus 50.0 versus 100.2 months for NY-ESO-1 (p = 0.0019). By multivariate analysis, these factors were confirmed as independent markers for poor survival. HNSCC patients showing protein expression of MAGE-A family members or NY-ESO-1 represent a subgroup with an extraordinarily poor survival. The development of immunotherapeutic strategies targeting these CTA may, therefore, be a promising approach to improve the outcome of HNSCC patients.

Since its first description by Marx in 2003, the etiology of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is the subject of numerous scientific discussions for oral and maxillofacial surgeons. Many retrospective studies on its etiology and pathogenesis have been carried out to explain pathological mechanisms; most of them just take a close look at the issue of dosage and application. Recently, attempts have been made, to identify co-factors which might promote the development of BRONJ.The present study is based on data of 169 patients with osseous metastatic malignancies. All patients received intravenous bisphosphonate therapy. On the basis of medical history, malignancy, and primary treatment, the modality of bisphosphonate therapy, and existing comorbidities and medication were analyzed. The role of immunosuppressive drugs, influence of underlying diseases, and general factors such as age and gender were examined. The predictability of necrotic involvement, influenced by the underlying malignancy and its specific therapy, e.g. radiation and cytostatic therapy were analyzed and statistically evaluated.A total of 8.9% (n=15) of patients developed BRONJ. The average time between diagnosis of malignancy and BRONJ was 80 months. Nine patients suffered from breast cancer, five had prostate cancer and one renal cancer. Separation into stage and histological subtype did not show any significant correlation, nor did age or gender, to the occurrence of BRONJ. However statistical analysis did show a significant correlation concerning monocytostatic (p=0.0215) and triple-cytostatic therapy (p=0.0137). The majority of patients with BRONJ (60%) received a bisphosphonate therapy including zoledronate. Single application with one bisphosphonate was administered in 28 cases; 44 patients had a medical history of different use of bisphosphonate. Concomitant medication did not suggest possible correlation, nor did accompanying diseases, arterial hypertension (33.33%) or arterial microcirculatory disturbances (20%).The evaluation of our results is pioneering. The influence of cytostatics and combined therapy of cytotoxic drugs on the pathogenesis of BRONJ is demonstrated here statistically. We confirmed a drug- and dose-dependent occurrence of BRONJ. Further prospective studies should be performed to elucidate the role of tissue perfusion and oxygen saturation, and the influence of immunosuppressive drugs in relation to the occurrence of BRONJ, as well as on wound healing of initial lesions.

Objectives To study immunohistochemical expression of the epithelial growth factor receptor (EGFR) in oral carcinomas and the head and neck region to examine possible associations with various features of the tumors and survival of the patients. Materials and methods Sections were made from two tissue arrays composed of 206 oral squamous cell carcinomas and 427 squamous cell carcinomas of the head and neck region, respectively, and examined for EGFR expression and Ki-67 labeling index by means of immunohistochemistry, and for EGFR gene amplification by means of fluorescence in situ hybridization. Correlation between resulting parameters and with clinical features was evaluated using chi-square test and Kaplan–Meyer analysis. Results A statistically significant association was observed for strong EGFR immunohistochemical (IHC) expression with advanced lymph node involvement (P = 0.02). EGFR immunohistochemical expression did not significantly correlate with patient disease specific (DS) or overall survival (OS). EGFR gene amplification was not correlated with any of the tumor features nor to survival of the patients (DS and OS). Discussion Epithelial growth factor receptor IHC expression and gene amplification might be suitable to predict locoregional control in oral squamous cell carcinoma patients but an inappropriate predictor for patients survival.

Early detection and complete resection of oral carcinomas is of crucial importance for patient survival. This could be significantly improved by developing a non-invasive, sensitive and real-time detection technique. Time-resolved autofluorescence measurement is state-of-the-art technology originally developed for non-destructive inspection of material. In this study, we measured time-resolved autofluorescence in tumours and healthy tissues of the oral cavity ex vivo and calculated the corresponding fractal dimension which was significantly higher in tumours than in healthy tissues (1.8 vs. 1.6, P