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The aim of the study was to compare incidences and types of injury incurred between e-scooter crashes and bicycle crashes. This retrospective study included all victims of e-scooter crashes who were treated in the department of oral and maxillofacial surgery during a 12-months interval.A comparison was made with a cohort of patients who underwent bicycle crashes. Study parameters included type of fracture, soft tissue and dental affection, necessity of inpatient or outpatient treatment, the use of helmets, and the time of admission. In total, 400 patients were included. Of these 40 had suffered a crash on an e-scooter and 360 on a bicycle. Descriptive statistics showed a low helmet-wearing rate among cyclists (16.1% of recorded cases), with no helmet wearing recorded among e-scooter users. E-scooter-related crashes showed a higher rate of facial soft-tissue injuries (77.5%, p = 0.049) than among cyclists (61.7%), as well as a higher rate of dental injuries (27.5%, p = 0.017) compared with the bicycle cohort (13.3%). Facial fractures were also more common in the e-scooter cohort (45% vs 25.8%, p = 0.010). Admission was typically at the weekend - in the afternoon for the bicycle cohort and in the evening and at night for the e-scooter cohort. As a consequence of the fact that e-scooter riders seem to have an increased risk of facial injuries, it seems that an awareness campaign might be necessary to encourage helmet usage and to persuade intoxicated persons to use public transportation instead.

The aim of the study was to analyze the role of temporal muscle and particularly tendon pathology in patients suffering from craniomandibular dysfunction (CMD) using magnetic resonance imaging.Retrospective analysis of MRI examinations was carried out with regard to temporal muscle fibrosis and fatty degeneration and particularly temporal tendon rupture, thickening, and degenerative signal alterations. Descriptive statistics and the Mann-Whitney U-test were used for statistical evaluation.Structural lesions of temporal muscle parenchyma were the absolute exception. PD hyperintensity, pronounced contrast enhancement, or peritendinous fluid collections along the temporal tendon were found only to a small extent, and a (partial) rupture occurred in only one case. The tendon diameter showed only slight variability. The Mann-Whitney U-test provided no results indicating a causal connection between degenerative joint or disc disease and temporal tendon pathology.A large sample of 128 magnetic resonance imaging examinations provided no evidence of a major role of temporal tendinitis in clinical CMD syndrome.· Retrospective analysis of temporal tendon in CMD patients.. · Abnormal structural findings along the tendon seen only rarely.. · Obviously no crucial role of temporal tendon lesions in CMD syndrome..· Stimmer H, Grill F, Waschulzik B et al. Temporal Tendinitis in Craniomandibular Dysfunction (CMD) - Does it Really Exist? A Temporomandibular MRI Investigation. Fortschr Röntgenstr 2022; 194: 1242 - 1249.ZIEL: Ziel der vorliegenden kernspintomografischen Untersuchung ist es, die Bedeutung von Läsionen des Musculus temporalis und insbesondere der Temporalissehne für das klinische Syndrom der kraniomandibulären Dysfunktion (CMD) zu untersuchen. In einer retrospektiven Analyse von MRT-Untersuchungen der Kiefergelenke wurden Fibrose und fettige Degeneration des Musculus temporalis und insbesondere Verdickung, degenerative Signalveränderungen und Ruptur der Temporalissehne beurteilt. Zur statistischen Auswertung kamen deskriptive Statistik und der Mann-Whitney-U-Test zur Anwendung. Strukturelle Läsionen des Musculus temporalis waren die absolute Ausnahme. Nur vereinzelt wurden ein Signalanstieg in PD-gewichteten Sequenzen, eine vermehrte KM-Aufnahme oder peritendinöse Flüssigkeitsansammlungen entlang der Temporalissehne gefunden, eine (Teil-)Ruptur der Sehne nur in einem Fall. Der Sehnendurchmesser zeigte nur eine geringe Variabilität. Der Mann-Whitney-U-Test erbrachte keine Hinweise auf eine kausale Verbindung zwischen degenerativer Gelenkerkrankung und Läsionen der Temporalissehne. In einer größeren Stichprobe von 128 MRT-Untersuchungen der Kiefergelenke fanden sich keine Hinweise auf eine wesentliche Rolle der temporalen Tendinitis beim klinischen Syndrom der kraniomandibulären Dysfunktion (CMD). · Retrospektive Analyse der Sehne des Musculus temporalis bei CMD-Patienten.. · Nur selten strukturelle Läsionen der Temporalissehne.. · Offensichtlich keine wesentliche Rolle von Läsionen der Temporalissehne beim klinischen CMD-Syndrom..

Background The objective of this study was to evaluate the diagnostic value of intraoperative frozen section analysis (IFSA) of tumor bed margins in patients with oral squamous cell carcinoma (OSCC). Methods This retrospective study includes 194 primary OSCC cases. The impact of intraoperative information by IFSA on final margin status, local recurrence, and disease-specific survival were analyzed. Results IFSA revealed a 50% sensitivity and a 100% specificity, with a positive and negative predictive value of 100% and 89.1%, respectively. In 19 cases, margins were rated positive by IFSA and remained positive in eight cases (42.1%), despite immediate re-resection. This constellation led to higher recurrence and lower survival rates than in cases with consecutive R0 status (each p = 0.046). Positive margins in IFSA were associated with closer final margins (p = 0.022) and early recurrences (p = 0.050). Conclusions Achieving instant R0 status has a crucial impact on disease recurrence and patient survival. IFSA falls short to ensure secure definite surgical margins. Thus, improved intraoperative diagnostic information on the location and extent of OSCC could support patient treatment. Clinical relevance Considering that patient survival has not improved despite progress in surgical and adjuvant therapy, the process and outcome of IFSA was scrutinized as one part of the treatment concept.

The aim of this study was to examine the lateral pterygoid muscle (LPM) parenchyma, myotendinous junction, and tendon in temporomandibular disorder (TMD) patients using 3T magnetic resonance imaging (MRI). Results were compared with findings reported in the literature, in which the LPM has been attributed a major role in triggering TMD. 3T MRI was used for temporomandibular joint (TMJ) imaging. The MRI images of 63 patients were analysed for muscle contracture and atrophy, tendon rupture, signal alterations of the tendon, tendon contrast enhancement, and peritendinous fluid collection. Descriptive statistics and the coefficient estimate method were used for statistical analysis. Focus was placed on the association between LPM tendon pathology and TMJ lesions like osteoarthritis and disc displacement. Severe lesions of the LPM tendon and muscle parenchyma, like rupture or fibrosis, were detected in very few cases. Only moderate signs of tendinosis were found in TMD patients. In contrast, there was a clear correlation between tendon lesions and osteoarthritis or anterior disc displacement. These results indicate the need to discuss and question the role of the LPM and its tendon in TMD. Data suggest that LPM and tendon lesions are part of complex degenerative changes of the TMJ, and it seems less likely that a LPM disorder is causative in TMD.

Objective: Fluorescence molecular imaging (FMI) has emerged as a promising tool for surgical guidance in oncology, with one of the few remaining challenges being the ability to offer quality control and data referencing. This paper investigates the use of a novel composite phantom to correct and benchmark FMI systems. Methods: This paper extends on previous work by describing a phantom design that can provide a more complete assessment of FMI systems through quantification of dynamic range and determination of spatial illumination patterns for both reflectance and fluorescence imaging. Various performance metrics are combined into a robust and descriptive "system benchmarking score," enabling not only the comprehensive comparison of different systems, but also for the first time, correction of the acquired data. Results: We show that systems developed for targeted fluorescence imaging can achieve benchmarking scores of up to 70 & x0025;, while clinically available systems optimized for indocyanine green are limited to 50 & x0025;, mostly due to greater leakage of ambient and excitation illumination and lower resolution. The image uniformity can also be approximated and employed for image flat-fielding, an important milestone toward data referencing. In addition, we demonstrate composite phantom use in assessing the performance of a surgical microscope and of a raster-scan imaging system. Conclusion: Our results suggest that the new phantom has the potential to support high-fidelity FMI through benchmarking and image correction. Significance: Standardization of the FMI is a necessary process for establishing good imaging practices in clinical environments and for enabling high-fidelity imaging across patients and multi-center imaging studies.

Integrins play important roles in physiological and pathophysiological processes. Among the RGD-recognizing integrin subtypes, the αvβ8 receptor is emerging as an attractive target because of its involvement in various illnesses, such as autoimmune diseases, viral infections, and cancer. However, its functions have, so far, not been investigated in living subjects mainly because of the lack of a selective αvβ8 ligand. Here, we report the design and potential medical applications of a cyclic octapeptide as the first highly selective small-molecule ligand for αvβ8. Remarkably, this compound displays low nanomolar αvβ8 binding affinity and a strong discriminating power of at least 2 orders of magnitude versus other RGD-recognizing integrins. Peptide functionalization with fluorescent or radioactive labels enables the selective imaging of αvβ8-positive cells and tissues. This new probe will pave the way for detailed characterization of the distinct (patho)physiological role of this relatively unexplored integrin, providing a basis to fully exploit the potential of αvβ8 as a target for molecular diagnostics and personalized therapy regimens.

High levels of reactive oxygen species (ROS) in tumors have been shown to exert anti-tumor activity, leading to the concept of ROS induction as therapeutic strategy. The organometallic compound ferrocene (Fc) generates ROS through a reversible one-electron oxidation. Incorporation of Fc into a tumor-targeting, bioactive molecule can enhance its therapeutic activity and enable tumor specific delivery. Therefore, we conjugated Fc to five synthetic, Arg-Gly-Asp (RGD)-based integrin binding ligands to enable targeting of the cell adhesion and signaling receptor integrin subtypes αvβ3, α5β1, or αvβ6, which are overexpressed in various, distinct tumors. We designed and synthesized a library of integrin-ligand-ferrocene (ILF) derivatives and showed that ILF conjugates maintained the high integrin affinity and selectivity of their parent ligands. A thorough biological characterization allowed us to identify the two most promising ligands, an αvβ3 (L2b) and an αvβ6 (L3b) targeting ILF, which displayed selective integrin-dependent cell uptake and pronounced ferrocene-mediated anti-tumor effects in vitro, along with increased ROS production and DNA damage. Hence, ILFs are promising candidates for the selective, tumor-targeted delivery of ferrocene to maximize its anti-cancer efficacy and minimize systemic toxicity, thereby improving the therapeutic window of ferrocene compared to currently used non-selective anti-cancer drugs.

Praoperativ werden umfassende onkologische Staging-Informationen gewonnen, um leitlinienorientierte Therapien fur Patienten mit Kopf-Hals-Karzinomen zu definieren. Die praoperativen onkologischen Informationen konnen jedoch nicht verlustfrei in die intraoperative Situation transferiert werden. Trotz der steten Entwicklung der modernen Medizin sind fur die intraoperative Detektion und Demarkierung malignen Gewebes lediglich klinische visuelle und taktile Informationen masgebend. Ziel der Arbeit war die Entwicklung einer intraoperativen spezifischen Visualisierung invasiver Karzinomzellen in Echtzeit. In Gewebe- und Zellkulturexperimenten wurden mittels Immun(fluoreszenz)histologie, Immunzytologie, Durchflusszytometrie (FACS), quantitativer Echtzeit-Polymerasekettenreaktion (qRT-PCR) und Western Blot die Expression und Regulation eines Biomarkers fur invasive Karzinomzellen charakterisiert. Funktionelle Analysen erfolgten durch Invasions- und Migrations-Assays. Fur In-vivo-Studien wurde ein „head and neck squamous cell carcinoma mouse-based patient-derived xenotransplant model“ (HNSCC-PDX-Mausmodell) etabliert, um eine Visualisierung invasiver Karzinome mittels funktionalisierten RGD-Peptide kliniknah zu simulieren. Das RGD bindende Integrin αvβ6 wurde als stabiler Biomarker invasiver Karzinomzellen identifiziert. Funktionalisierte RGD-Peptide zeigten eine selektive Bindung an Integrin αvβ6 zur Detektion αvβ6-positiver invasiver Karzinomzellen. Im HNSCC-PDX-Mausmodell konnte eine molekulare Bildgebung invasiven Karzinomgewebes (Bioimaging) etabliert werden. Ein molekulares Bioimaging ermoglicht eine erweiterte Visualisierung der Lokalisation und Ausdehnung invasiven Karzinomgewebes in Echtzeit. Dieser intraoperative Informationsgewinn kann kurative chirurgische Therapieansatze unterstutzen.

The intraoperative cytological assessment of bony resection margins (ICAB) is a feasible diagnostic approach to support frozen section for assessment of invasion of margins of soft and hard tissue. However, complex resection margins could challenge both diagnostic approaches. Our objective here was to identify the limitations of intraoperative diagnostic methods for assessing margins. We present an advanced cytological approach to assess complex margins that may solve the problem. Data from 119 patients in whom frozen section was supported by ICAB, were reviewed and the reasons for false results analysed. In 35 patients with squamous cell carcinoma infiltrating bone, specimens (n=100) from the resection margin went through an intraoperative cell isolation process for the cytological assessment of bony margins (ICAB). The results were compared with the histological results of the corresponding margins of bone as a reference. Limitations to the assessment of operative bony margins intraoperatively included an infiltrative histological pattern of growth of the carcinoma, with carcinoma cells disseminated within the cancellous bone, complex and uneven resection margins with soft and bony tissue, inflammation, and signs of previous radiotherapy. Intraoperative cell isolation plus (ICICAB) allowed the microscopic assessment of up to 1cm3 of bony tissue to detect disseminated carcinoma cells within the cancellous bone with a sensitivity of 92.3% (95% CI 74.9% to 99.1%), and a specificity of 100% (95% CI 95.1% to 100%), and positive and negative predictive values of 100% (95% CI 85.8% to 100%) and 97.4% (95%CI 90.8% to 99.7%), respectively. Intraoperative cell isolation is a feasible new technique to support ICAB and frozen section in the assessment of bony and soft tissue margins.

Background In 2012, a guideline for the diagnosis and treatment of oral cavity cancer based on the best available evidence was implemented at certified German cancer centres for head and neck carcinomas. The present analysis was performed to determine whether the implementation of the guideline via certification improved the level of care, leading to a benefit for the patients. Methods A prospective observational study was performed based on the annual operating figures at 31 certified head and neck cancer centres. From 76 statements and recommendations, 9 indicators were derived defining important steps during treatment. The annual shift of the figures was documented for each indicator and was used to measure the impact of the guideline. This was achieved by determining the number of patients having received the recommended treatment related to the total number in each centre over a period of 3 years. Results In 2014, 1570 primary cases with an oral cavity carcinoma were treated at our centres, 31.2% representing stage IVA. Except for two, all indicators showed increasing numbers of achievement from 2012 to 2014, reaching median values between 91% and 100% in 2014. In particular, median values for imaging and interdisciplinary treatment to evaluate the presence of second primaries and metastases increased by 20% and 30%, respectively. Median values decreased by 14% for recommended adjuvant radiation, because of non-acceptance by the patients. Moreover, elective neck dissection was performed less frequently in cN0 categories. Conclusions Implementation of the national cancer guideline by means of certification evidently had a positive impact on patients suffering from oral squamous cell carcinoma and led to the improved achievement of most evidence-based treatment recommendations over time. Further research involving high-level clinical studies is needed to cover all aspects of this specific tumour entity.

Background Imaging provides crucial staging information for treatment planning of head and neck squamous cell carcinomas (HNSCCs). Despite technical progress in imaging techniques, defining the extent of bone involvement preoperatively remains challenging and requires intraoperative information to control for adequate resection. The intraoperative cytological assessment of the bone resection margins (ICAB) provides information whether bone is infiltrated by carcinoma. The aim of this study was to assess the diagnostic value of preoperative imaging compared with ICAB in order to achieve carcinoma-free bone margins. Materials and Methods 108 HNSCC patients underwent preoperative computed tomography (CT), magnetic resonance imaging (MRI) and orthopantomogram (OPG) for staging and surgical planning. Curative resection was planned based on imaging. Intraoperatively, the resection margins were controlled by ICAB. The diagnostic value of preoperative imaging and ICAB was assessed with reference to the histological findings. Results CT showed a sensitivity of 89.7%, specificity of 63.0%, positive predictive value (PPV) of 85.9%, and negative predictive value (NPV) of 70.8%. MRI revealed a sensitivity of 45.5%, specificity of 66.7%, PPV of 71.4% and NPV of 40.0%. OPG-imaging had a sensitivity of 64.7%, specificity of 76.2%, PPV of 81.5%, NPV 57.1%. In comparison, ICAB provided a sensitivity of 78.6%, specificity of 95.7%, PPV 73.3%, and NPV 96.7%. The accuracy was 82.1%, 52.9%, 69.0%, and 93.5% for CT, MRI, OPG, and ICAB, respectively. Conclusion Preoperative imaging lacks accuracy in defining adequate bone resection margins, compared with ICAB. ICAB supports preoperative imaging and intraoperative frozen sections to improve bone margin control.

Fluorescence-guided intervention is increasingly considered for real-time intra-operative oncological applications. Herein we propose a novel composite phantom for standardization and quality control, which could serve as a framework toward good clinical practices.

Bacterial resistance against antibiotics has become an increasing challenge in the treatment of cutaneous infections. Consequences can be severe, especially in infected wounds following previous local radiotherapy. Certain endogenous peptide antibiotics, the host defence peptides (HDPs), exhibit broad-spectrum antimicrobial activity and promote wound healing. Their use as supplements to conventional antibiotics is a current topic of discussion; however, knowledge of their quantities in healthy and compromised tissue is a prerequisite for such discussion. To date, no data concerning HDP quantities in irradiated skin are available.Expression profiles of the genes encoding HDPs, namely human beta-defensin-1 (DEFB1, hBD-1), beta-defensin-2 (DEFB4A, hBD-2), beta-defensin-3 (DEFB103, hBD-3) and S100A7, were assessed in samples of non-irradiated and irradiated neck.A reduction in the expression of all of the examined genes was observed in irradiated skin when compared with non-irradiated skin (statistically significant in the case of S100A7, P = 0.013). Immunohistochemistry revealed differences in HDP distribution with respect to the epithelial layers.The study demonstrates a significant reduction in HDP gene expression in neck skin as a result of radiotherapy. These findings might represent a starting point for novel treatments of cutaneous infections in irradiated patients, such as topical supplementation of synthetic HDP.

Objective To investigate disease recurrence among patients with oral squamous cell carcinoma (OSCC) and positive lymph node lesions receiving different therapy for different stages of the disease. Study Design One hundred sixty-one patients with biopsy-proven pN1 and pN2+ carcinomas were reviewed retrospectively. We investigated postoperative disease recurrence when using surgery alone (SA), adjuvant radiotherapy (RT), or adjuvant radiochemotherapy (RCT) and compared our results with the 2012 German guidelines. Results Among the study population, 60 (37%) experienced postoperative disease recurrence, 38% with SA, 42% with adjuvant RT, and 39% with adjuvant RCT (P = .420). In the case of pN1, the recurrence rate was 14% with SA, 32% with RT, and 33% with RCT (P = .156); and in pN2+, 60%, 49%, and 29%, respectively (P = .012). Conclusions Surgery plus adjuvant therapy has benefits with respect to postoperative disease recurrence in pN2+ OSCC. In pN1, surgery alone might be as effective as adjuvant RT or RCT.

We assessed the use of peptides containing arginylglycylaspartic acid (RGD) that target integrin αvβ6 as a potential approach for a fluorescence-assisted intraoperative cytological assessment of bony resection margins (F-AICAB) in patients who had bone-infiltrating squamous cell carcinoma (SCC) of the head and neck. This was assessed to demarcate invasive carcinoma cells that stained for αvβ6. Specimens from bony resection margins (n=362) were defined as either malignant or benign according to the results of cytological and histological examinations. Integrin αvβ6-targeting fluorescence-labelled RGD peptides were added to the cytological samples and the accuracy of the resulting signal assessed by comparing it with the cytological findings. The value of F-AICAB was evaluated to find out if it could help to improve future diagnoses, tests, and treatments. Integrin αvβ6 was strongly expressed in invasive SCC cells and qualified as a marker for bone-infiltrating carcinoma cells. It showed a high affinity to bind to invasive SCC cells and enabled swift and specific demarcation of αvβ6-stained carcinoma cells. It was also diagnostic, with a sensitivity of 100% (95% CI 81.3% to 99.3%), specificity of 98.3% (95% CI 94.4% to 99.0%), positive predictive value of 92% (95% CI 70.2% to 94.3%), and negative predictive value of 100% (95% CI 96.9% to 99.9%), compared with the cytological findings. The targeting of specific integrin subtypes with selective, synthetic ligands, adapted for multimodal imaging, is a promising new approach to diagnosis. Further studies are necessary to provide more evidence for successful clinical translation and to establish the impact on clinical procedures.

BACKGROUND Frozen sections are routinely applied to control for adequate resection margins. In cases in which carcinoma infiltrates bone, the intraoperative microscopic assessment of bone margins remains challenging due to technical difficulties to section native bone. The objective of the current study was to evaluate an intraoperative cytological approach to control bone resection margins in patients with bone-infiltrating oral squamous cell carcinomas. METHODS A total of 174 cytological preparations obtained from bone margins of bone-infiltrating oral squamous cell carcinomas (28 patients) were assessed intraoperatively and compared with the corresponding histological findings. In a validation cohort (45 patients) the intraoperative cytological assessment of bone resection margins (ICAB) (104 margins) was evaluated as a diagnostic tool for routine clinical application. RESULTS In the first patient cohort, the ICAB revealed 95.3% sensitivity and 96% specificity. The results provided an accuracy of 95.7% with a significant correlation noted between cytological and histological results (κ, 0.91; P

Submandibular acinar glands secrete numerous proteins such as digestive enzymes and defense proteins on the basis of the exocrine secretion mode. Exocytosis is a complex process, including a soluble NSF attachment protein receptor (SNARE)–mediated membrane fusion of vesicles and target membrane and the additional activation of cytoskeletal proteins. Relevant data are available predominantly for animal salivary glands, especially of the rat parotid acinar cells. The authors investigated the secretory molecular machinery of acinar (serous) cells in the human submandibular gland by immunohistochemistry and immunofluorescence and found diverse proteins associated with exocytosis for the first time. SNAP-23, syntaxin-2, syntaxin-4, and VAMP-2 were localized at the luminal plasma membrane; syntaxin-2 and septin-2 were expressed in vesicles in the cytoplasm. Double staining of syntaxin-2 and septin-2 revealed a colocalization on the same vesicles. Lactoferrin and α-amylase served as a marker for secretory vesicles and were labeled positively together with syntaxin-2 and septin-2 in double-staining procedures. Cytoskeletal components such as actin, myosin II, cofilin, and profilin are concentrated at the apical plasma membrane of acinar submandibular glands. These observations complement the understanding of the complex exocytosis mechanisms.

Proteomic analysis recently suggested aberrant psoriasin (S100A7) expression in oral squamous cell carcinoma (OSCC). In this study, OSCC specimens and matching normal oral tissues from 45 patients who had undergone ablative surgery were examined. Increased psoriasin expression at mRNA level was observed in OSCC samples by quantitative real-time RT-PCR (p=0.015). Immunofluorescence analysis with psoriasin antibody confirmed these observations. Moreover, significantly increased mRNA ratios between malignant and normal samples were correlated with early UICC stage (p=0.006), T1/T2 tumour classification (p=0.043), absence of cervical lymph node metastasis (p=0.027) and age under 65 (p=0.009). Additionally, well-differentiated tumour tissues demonstrated a significantly higher psoriasin expression than moderate and poor differentiated carcinomas (p=0.018). Based on this data, we conclude that psoriasin is a positive marker for oral cancerogenesis and early tumour progression.

Squamous cell carcinoma (SCC) in the head and neck is associated with synchronous or metachronous carcinomas of the lung. Preoperative pulmonary screening is advocated and may be done by bronchoscopy, thoracic radiograph, computed tomography (CT), or positron emission tomography (PET) with CT (PET/CT fusion). We evaluated the role of bronchoscopy in patients with primary oral SCC to ascertain the incidence of synchronous malignancies of the lung. We retrospectively reviewed a decade's experience of screening by bronchoscopy in 570 pathologically confirmed and previously untreated patients with oral SCC (188 female, 382 male). Univariate and multivariate analyses were done after evaluating the incidence of synchronous lesions and the clinical and histological features of the index tumour. Investigation by bronchoscopy showed disease in 166 patients, and malignancy of the lung in 9 (2%). The Union International contre le Cancer (UICC) stages I and II oral SCC were significantly associated with a synchronous malignancy of the lung (p=0.038). We recommend the use of bronchoscopy even in early tumour stages. Some patients had their treatment altered because of its use, including upstaging, diagnosis of distant and unresectable disease, and investigation of second primary malignancies.

The αvβ6 integrin binds the RGD-containing peptide of the foot and mouth disease virus with high selectivity. In this study, the long binding helix of this ligand was downsized to an enzymatically stable cyclic peptide endowed with sub-nanomolar binding affinity toward the αvβ6 receptor and remarkable selectivity against other integrins. Computational studies were performed to disclose the molecular bases underlying the high binding affinity and receptor subtype selectivity of this peptide. Finally, the utility of the ligand for use in biomedical studies was also demonstrated here. The search for binding: The αvβ6 integrin binds the RGD-containing peptide of the foot and mouth disease virus with high selectivity. The long binding helix of this ligand was downsized to an enzymatically stable cyclic peptide endowed with sub-nanomolar binding affinity toward the αvβ6 receptor and remarkable selectivity against other integrins.

Secretory cells in the seromucous glands of paranasal sinuses secrete antibacterial proteins for innate immune mucosal integrity. We studied the localization of antimicrobial and cytoskeletal components of the human seromucous glands and respiratory epithelium of the maxillary sinus and the ethmoidal cells by immunohistochemical methods. The presence of a variety of defense proteins such as lysozyme, lactoferrin, cathelicidin, and defensin-1, -2, -3 point to a crucial role in the immune defense for the respiratory tract. Cytoskeletal proteins such as actin, myosin 2, cytokeratin 7 and 19, α- and β-tubulin, investigated for the first time in glands of paranasal sinuses, showed a stronger expression at the apical and lateral cell membrane. The localization of the cytoskeletal proteins might point to their participation in exocrine secretory processes and stabilizing effects.

Frozen sections are routinely applied to control for adequate resection margins. In cases in which carcinoma infiltrates bone, the intraoperative microscopic assessment of bone margins remains challenging due to technical difficulties to section native bone. The objective of the current study was to evaluate an intraoperative cytological approach to control bone resection margins in patients with bone-infiltrating oral squamous cell carcinomas.A total of 174 cytological preparations obtained from bone margins of bone-infiltrating oral squamous cell carcinomas (28 patients) were assessed intraoperatively and compared with the corresponding histological findings. In a validation cohort (45 patients) the intraoperative cytological assessment of bone resection margins (ICAB) (104 margins) was evaluated as a diagnostic tool for routine clinical application.In the first patient cohort, the ICAB revealed 95.3% sensitivity and 96% specificity. The results provided an accuracy of 95.7% with a significant correlation noted between cytological and histological results (κ, 0.91; P.001), and a positive predictive value and negative predictive value of 93.8% and 96.9%, respectively. In the validation cohort, ICAB revealed 80% sensitivity and 98.9% specificity with 98% accuracy. There was a significant correlation found between cytological and histological results (κ, 0.91; P.001), providing a positive predictive value and negative predictive value of 80% and 98%, respectively. ICAB could predict final resection status at bone margins with 80% sensitivity and 97.5% specificity. A significant correlation was found between the cytological and histological resection status at bone margins (κ, 0,75; P.001).ICAB could supplement intraoperative frozen sections of soft tissue margins as a standard procedure to control for adequate resection at bone margins.

Host defence peptides (HDPs), including human β-defensins (hBDs) and psoriasin/S100A7, exert antimicrobial and immunoregulatory functions of the innate defense system. In addition to these functions, the search for cancer biomarkers has identified HDPs as playing a potential role in both tumor suppression and oncogenesis. Although HDPs are highly expressed in salivary glands, their role as molecules for potential diagnostic and therapeutic approaches has not yet been analyzed.The aim of the present study was to investigate whether expression levels of putative pro- or anti-oncogenic hBDs, including hBD-1, -2, -3, and psoriasin/S100A7, are altered in salivary gland tumor tissue as potential targets for molecular-based therapeutic approaches.We analyzed the expression levels of hBD-1, -2, -3, and psoriasin/S100A7 by quantitative real-time polymerase chain reaction (qrt-PCR) and immunohistochemistry in a case control study by comparing salivary gland tumor samples relative to healthy control specimens from 58 patients. Expression level analysis of hBD-1, -2, -3, and psoriasin/S100A7 by qrt-PCR was normalized to the endogenous 18S rRNA expression levels.The results demonstrate the significant downregulation of hBD-1 (p 0.001), hBD-2 (p = 0.003), hBD-3 (p = 0.002), and psoriasin/S100A7 (p = 0.003) mRNA in human salivary gland tumors compared with healthy control specimens. Protein expression levels of hBD-1, -2, -3, and psoriasin/S100A7 in salivary gland tumor tissue were strongly reduced compared with healthy control specimens.The data indicates a putative role of the innate defense system in salivary gland tumor formation. The identification of immunoregulatory molecules as diagnostic biomarkers or therapeutic targets could provide new approaches for molecular-based diagnostic and therapeutic support to treat salivary gland tumors as well as other malignancies. We suggest that HDPs should be taken into consideration for use in molecular-based therapeutic approaches.

Purpose Oral squamous cell carcinoma (OSCC) represents more than 90% of oral malignancies. Risk factors such as smoking and alcohol abuse can result in additional diseases, particularly of the upper gastrointestinal tract. The aim of the present study was to assess the synchronous pathologic changes of the upper gastrointestinal tract using endoscopy at the diagnosis of OSCC using a retrospective cohort study design. Patients and Methods The clinical records of 806 patients with OSCC from 1997 to 2007 were reviewed. Of the 806 patients, 570 (188 females and 382 males) with primary OSCC were identified. All patients underwent esophagogastroduodenoscopy at the initial tumor staging. The tumor stage was defined according to the International Union Against Cancer classification for head and neck malignancies. The clinical and histologic data were analyzed for probability using univariate and multivariate analyses. Results Of the 570 patients, 289 had limited and 281 advanced disease. A statistically significant association was found between the advanced and limited tumor stage for Barrett's esophagus with an odds ratio of 4.986 (95% confidence interval 1.370 to 27.360, P = .0061). Pathologic findings were observed in 169 patients. Additional risk factors for the development of secondary upper aerodigestive tract cancers were found in 103 patients. Conclusions Esophagogastroduodenoscopy provides the opportunity to identify second malignancies, precancerous lesions, and risk factors and to obtain biopsies using one procedure. The results can be immediately integrated into the therapeutic concept of the primary disease. Although new imaging techniques have been available, esophagogastroduodenoscopy still plays a decisive role in the routine staging of OSCC.

Integrins are key regulators of communication between cells and with their microenvironment. Eight members of the integrin superfamily recognize the tripeptide motif Arg-Gly-Asp (RGD) within extracelluar matrix (ECM) proteins. These integrins constitute an important subfamily and play a major role in cancer progression and metastasis via their tumor biological functions. Such transmembrane adhesion and signaling receptors are thus recognized as promising and well accessible targets for novel diagnostic and therapeutic applications for directly attacking cancer cells and their fatal microenvironment. Recently, specific small peptidic and peptidomimetic ligands as well as antibodies binding to distinct integrin subtypes have been developed and synthesized as new drug candidates for cancer treatment. Understanding the distinct functions and interplay of integrin subtypes is a prerequisite for selective intervention in integrin-mediated diseases. Integrin subtype-specific ligands labelled with radioisotopes or fluorescent molecules allows the characterization of the integrin patterns in vivo and later the medical intervention via subtype specific drugs. The coating of nanoparticles, larger proteins, or encapsulating agents by integrin ligands are being explored to guide cytotoxic reagents directly to the cancer cell surface. These ligands are currently under investigation in clinical studies for their efficacy in interference with tumor cell adhesion, migration/invasion, proliferation, signaling, and survival, opening new treatment approaches in personalized medicine.