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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.

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.

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

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.

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.