[Open educational resources for otorhinolaryngology : A pilot study on needs assessment and implementation]. / Open Educational Resources für die HNO-Heilkunde : Ein Pilotprojekt zur Bedarfsanalyse und Implementierung.

BACKGROUND: Open educational resources (OER) are educational materials licensed openly by authors, permitting usage, redistribution, and in some instances, modification. OER platforms thereby serve as a medium for distributing and advancing teaching materials and innovative educational methodologies. OBJECTIVE: This study aims to determine the present state of OER in otorhinolaryngology and to examine the prerequisites for seamlessly integrating OER into the curricular teaching of medical schools, specifically through the design of two OER blended learning modules. METHODS: OER content in the field of otorhinolaryngology was analyzed on OER platforms, ensuring its relevance to the German medical curriculum. Data protection concerns were addressed with legal counsel. The blended learning modules were developed in collaboration with medical students and subsequently published as OER. RESULTS AND CONCLUSION: This project yielded the first OER from a German ENT department, tailored to the German medical curriculum. One significant barrier to OER use in medicine, more than in other fields, is data protection. This challenge can be navigated by obtaining consent to publish patient data as OER. OER hold the promise to play a pivotal role in fostering cooperation and collaboration among educators, aiding educators in lesson preparation, and simultaneously enhancing didactic quality.

Traditional risk factors and nodal yield-still relevant with high-quality risk-adapted adjuvant treatment for locally advanced head and neck cancer?

OBJECTIVE: Patients with locally advanced head and neck cancer (LAHNC) often undergo multimodal therapy including radical resection of the primary tumor and neck dissection (ND) followed by risk-adapted adjuvant radio(chemo)therapy (R(C)T). Quality parameters influencing local control and survival of these patients have been postulated: resection status (R status), extranodal extension (ENE), interval to adjuvant treatment ≤6 weeks, R(C)T given when indicated, and nodal yield (NY) ≥18 lymph nodes per neck. For other solid tumors the trend is towards less extensive lymph node surgery to avoid toxicity such as lymphedema, damage to peripheral nerves, dysesthesia, or paresthesia. The present study aims to investigate whether the number of nodes removed during neck dissection for LAHNC is still predictive for outcome when patients receive risk-adapted adjuvant treatment according to current guidelines. METHODS: Between 2008 and 2015, 468 patients with LAHNC undergoing R(C)T with curative intent were prospectively registered in a database (UICC III/IV). Among them, 359 patients received adjuvant treatment and 295 underwent neck dissection. There were 119 (40%) patients with an oropharyngeal primary, 49 (17%) with cancer of the larynx/hypopharynx, 88 (30%) of the oral cavity, and 39 (13%) of the nasal/paranasal sinuses and cancer of unknown primary (CUP). Median follow-up was 45.6 months. Histopathology revealed an R1 status in 65 (22%) cases and ENE in 93 (31%) cases. 150 (51%) patients received RCT; the median time to adjuvant treatment from the day of tumor resection was 44 days (35-54) and overall treatment time (OTT; time from surgery to the last day of R(C)T) was 90 days (82-101). Factors influencing disease-free survival (DFS) were adjusted and analyzed using CART analysis (removed nodes, number of positive nodes, body mass index (BMI), ENE, T and N classification, R status, and primary site). Local control (LC), distant metastases-free survival (DMFS), and overall survival (OS) were analyzed using Kaplan-Meier statistics and multivariate analysis (MVA) for factors predictive for DFS and OS. RESULTS: CART analysis (Classification and Regression Trees) showed that T classification (T3/4) is the most important predictor for DFS, followed by age (> 61 years) and BMI (< 17.4). Primary site (OPC vs. other) and number of removed nodes (< 17) were shown to be less important for DFS, while ECE, N classification, and R status seem to be of little relevance. MVA revealed number of positive nodes, non-OPC, and T3/4 to be negative predictive factors for DFS. For OS, the number of positive nodes and non-OPC primary were predictive. Five-year rates were 86.1% for LC, 87.9% DMFS, 76.5% DFS, and 67.2% for OS. CONCLUSION: In this patient cohort, the number of removed nodes is not relevant for DFS and OS, while the number of positive nodes and T classification have a negative impact on these endpoints. The high-risk factors positive resection margin and ECE seem to lose their negative impact on DFS and OS. High-quality care in head and oncology is only possible within a close multidisciplinary team and network.

Influence of radiation dose to pharyngeal constrictor muscles on late dysphagia and quality of life in patients with locally advanced oropharyngeal carcinoma.

BACKGROUND AND OBJECTIVE: Patients with oropharyngeal carcinoma (OPC) often have difficulty swallowing, which may affect quality of life (QoL). Radiation dose to constrictor muscles plays an important role. METHODS: 54 patients with locally advanced OPC were evaluated after intensity-modulated radiotherapy. Data were collected at standardized intervals using the EORTC questionnaires QLQ-C30 and QLQ-HN35 within two years. The pharyngeal constrictors (superior, middle, and inferior) were each contoured as an organ at risk. Influence of dose to the constrictors (≥55 Gy vs. <55 Gy) on late dysphagia and QoL was analyzed using the t­test. RESULTS: Late radiation-induced dysphagia depends significantly on the dose to the lower pharyngeal constrictor. At a dose of ≥55 Gy, 14 (64%) patients developed dysphagia grade ≤2 and 8 (36%) patients grade ≥3. At a dose of <55 Gy, the distribution at the end of radiotherapy (RT) was similar: 22 (69%) patients with dysphagia grade ≤2, 10 (31%) with grade ≥3. There was no dose-dependent difference in the severity of dysphagia in the acute phase (p = 0.989). There were differences 18 months after the end of RT: ≥55 Gy: 19 (86%) patients showed dysphagia grade ≤2; 3 (14%) grade ≥3. At <55 Gy, 31 (97%) patients developed grade ≤2, 1 (3%) grade ≥3 (18 months: p = 0.001; 24 months: p = 0.000). Late dysphagia is also dependent on the dose level of the middle constrictor muscle (6 months: p = 0.000; 12 months: p = 0.005, 18 months: p = 0.034). After 24 months, there was no significant difference (p = 0.374). CONCLUSION: Radiation dose to the upper constrictor muscle appears to be of little relevance. The middle and lower constrictor should be given special consideration to avoid late dysphagia. Long-term QoL is independent on radiation dose.

Inhibition of ornithine decarboxylase restores hypoxic pulmonary vasoconstriction in endotoxemic mice.

Endotoxemia impairs hypoxic pulmonary vasoconstriction which leads to systemic hypoxemia. This derogation is attributable to increased activity of nitric oxide synthase 2 and arginase metabolism. Gene expression analysis has shown increased expression of ornithine decarboxylase in lungs of endotoxemic mice, a downstream enzyme of arginase metabolism. The aim of this study was to investigate whether inhibition of ornithine decarboxylase increases hypoxic pulmonary vasoconstriction in lungs of endotoxemic mice. Mice received lipopolysaccharides or saline intraperitoneal, and hypoxic pulmonary vasoconstriction was measured using an isolated perfused mouse lung model. Additional mice with and without endotoxemia were pretreated with the ornithine decarboxylase-inhibitor difluoromethylornithine before examination of hypoxic pulmonary vasoconstriction. Hypoxic pulmonary vasoconstriction was defined as the difference of pulmonary arterial pressure between normoxic and hypoxic ventilation. In addition, lung tissue was analyzed using real-time quantitative polymerase chain reaction, Western blot and immunohistochemistry. Lipopolysaccharides caused an up-regulation of ornithine decarboxylase mRNA level (2.73 ± 0.19-fold increase, p < 0.05) as well as ornithine decarboxylase protein level (4.05 ± 0.37-fold increase, p < 0.05). Endotoxemia attenuated hypoxic pulmonary vasoconstriction when compared with untreated control mice (26.3 ± 9.7% vs. 67.0 ± 17.5%). Difluoromethylornithine (20, 100, 500 mg kg-1 body weight intraperitoneal) restored hypoxic pulmonary vasoconstriction in lungs of endotoxemic mice in a dose-dependent way (25.8 ± 9.9%, 57.3 ± 17.2%, 62.3 ± 12.4%) and decreased hypoxic pulmonary vasoconstriction in control mice (53.6 ± 13.6%, 40.0 ± 14.9%, 35.9 ± 12.4%). These results show that endotoxemia induces ornithine decarboxylase expression and suggest that ornithine decarboxylase contributes to the endotoxemia-induced impairment of hypoxic pulmonary vasoconstriction. Inhibition of ornithine decarboxylase might be a target in the therapy of diseases with inflammation impaired hypoxic pulmonary vasoconstriction, like the sepsis-associated acute respiratory distress syndrome (ARDS).

[Treatment of head and neck squamous cell carcinoma recurrences and distant metastases : Highlights of the 2019 ASCO Meeting]. / Therapie der rezidivierten und fernmetastasierten Plattenepithelkarzinome des Kopf-Hals-Bereichs : Highlights des ASCO-Meetings 2019.

BACKGROUND: The contributions presented at this year's ASCO conference on treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC) focused on systemic therapies, as in recent years. Two phase III studies-TPExtreme and Keynote-048-are expected to change clinical practice in first-line treatment of R/M-HNSCC. MATERIALS AND METHODS: Abstracts and presentations from this year's ASCO Annual Meeting on R/M-HNSCC were screened and checked for clinical relevance. RESULTS: TPExtreme, a randomized phase III trial, could show less toxicity and similar overall survival in patients treated with docetaxel, cisplatin, and cetuximab (TPEx regimen) compared to standard first-line therapy with the Extreme regimen (cisplatin, 5­fluorouracil [5-FU], cetuximab), albeit failing its endpoint of significantly improved survival. The randomized phase III Keynote-048 study could show a significant survival benefit in all patients treated with pembrolizumab, 5­FU, and cis-/carboplatin compared to Extreme. When selected patients (PD-L1 CPS ≥1 and ≥20) were treated with pembrolizumab monotherapy, they showed increased overall response rates in contrast to patients treated with Extreme. CONCLUSION: Based on the results of Keynote-048, pembrolizumab ± chemotherapy gained FDA approval as first-line treatment for R/M-HNSCC in the USA. Approval in Europe is expected soon and will probably have a strong impact on clinical routine.

[Immunotherapy for head and neck cancer : Highlights of the 2019 ASCO Annual Meeting]. / Immuntherapie von Kopf-Hals-Tumoren : Highlights der ASCO-Jahrestagung 2019.

BACKGROUND: In the field of immunotherapy of head and neck squamous cell carcinoma (HNSCC), a high level of study activity can still be observed. The results of the Keynote-048 study on first-line therapy with pembrolizumab were a highlight at this year's meeting of the American Society of Clinical Oncology (ASCO). MATERIALS AND METHODS: All abstracts and presentations on immunotherapy of head and neck tumors presented at ASCO 2019 were evaluated for relevance and the most interesting studies were summarized. RESULTS: The Keynote-048 study showed an improvement in overall survival with pembrolizumab monotherapy for patients with measurable programmed cell death ligand 1 (PD-L1) expression according to the combined positive score (CPS), and for the whole cohort with the combination of pembrolizumab and platin/5-fluorouracil (FU). The EAGLE study on durvalumab ± tremelimumab in second-line therapy did not demonstrate any improvement in response rates or overall survival compared to standard therapy. In addition, several new immunotherapeutic approaches and combinations were presented. CONCLUSION: The results of the Keynote-048 study have already led to the approval of pembrolizumab in the first line for platin-sensitive HNSCC in the USA and the expected approval in Europe will presumably change the therapeutic landscape in the long term. In the future, effective therapies for patients without a response to programmed cell death 1 (PD-1)/PD-L1 inhibition will be needed.

Tumor volume as a predictive parameter in the sequential therapy (induction chemotherapy) of head and neck squamous cell carcinomas.

PURPOSE: Tumor volume in locally advanced head and neck squamous cell carcinomas (LAHNSCC) treated by induction chemotherapy (ICT) and followed by radiochemotherapy (RCT) was measured. The presence of potential correlation of initial tumor volume and volume reduction after ICT and RCT with remission status, overall survival (OS) and disease-free survival (DFS) were investigated. Furthermore, reliability of approximation of the tumor volume relying on its diameter to manual three-dimensional measurement was assessed. METHODS: Data of patients with LAHNSCC treated by ICT consisting of docetaxel, cisplatin, and 5-fluorouracil (TPF) followed by definite RCT were retrospectively analyzed. The tumor volume was calculated slice-by-slice in contrast-enhanced CT or MRI before and after ICT as well as after complete treatment. The volume was compared to radiologic remission status, correlated with OS and DFS, and to volume estimation using tumor diameter. RESULT: 65 patients were included. Primary tumor volume did not correlate with complete remission rate (CR) after ICT and RCT, OS or DFS. The change in tumor volume between baseline imaging and post-RCT had a significant impact on OS (p = 0.026) and DFS (p = 0.028). The agreement between tumor volume and radiologic remission was 72.14%. CONCLUSION: The initial tumor volume had no influence on CR, OS or DFS. A severe response to ICT did not predict a powerful RCT outcome. The change in tumor volume post-RCT had an impact on OS and DFS. Tumor volume estimation using its diameter seems to be a reliable method.

[Treatment of head and neck squamous cell carcinoma recurrences and distant metastases : Highlights of the 2018 ASCO meeting]. / Therapie der rezidivierten und fernmetastasierten Plattenepithelkarzinome des Kopf-Hals-Bereichs : Highlights des ASCO-Meetings 2018.

This year, the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC) was mainly dominated by immunotherapy. The corresponding studies are presented in another article. Beside this, results of phase II studies in particular were presented at the ASCO Annual Meeting, in which-as in recent years-new drugs (monoclonal antibodies, small molecules) played a major role. Furthermore, a clinical scoring system for prognosis evaluation in R/M-HNSCC patients was presented and the influence of HPV status on survival in this patient cohort was investigated. The studies presented herein reflect the different drug-based treatment concepts in R/M-HNSCC and represent the variety of therapeutic approaches in the recurrent and metastatic setting.

[Immunotherapy highlights of the ASCO annual meeting 2018 for head and neck cancers]. / Highlights der ASCO Jahrestagung 2018 zur Immuntherapie von Kopf-Hals-Tumoren.

BACKGROUND: Immunotherapeutic strategies are becoming increasingly more important for head and neck cancer and numerous clinical trials were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) 2018. OBJECTIVE: In this review the most interesting clinical trials and trial results for immunotherapy of head and neck cancer are summarized. MATERIAL AND METHODS: All abstracts and presentations on immunotherapy of head and neck cancer at the annual meeting of the ASCO 2018 were screened to select the most interesting trials for a more detailed analysis. RESULTS: For head and neck cancer, practice changing phase III trial results were missing, but several noteworthy new strategies and trial results for immunotherapy were presented. Neoadjuvant immunotherapy trials, results concerning immunotherapy in old age, prognostic implications of immune-mediated adverse events and new immunotherapy combinations are summarized in this article. CONCLUSION: The role of immunotherapy for the treatment of head and neck cancer is markedly increasing. Many pioneering trials are currently ongoing, in the phase of data analysis or in planning.

Socioeconomic status and quality of life in patients with locally advanced head and neck cancer.

PURPOSE: Socioeconomic aspects play an important role in health care. Patients with locally advanced head and neck cancer (LAHNC) experience detrimental effects on their quality of life (QoL). This prospective study examines QoL differences between patients with different socioeconomic status (SES) after intensity-modulated radiation therapy (IMRT). PATIENTS AND METHODS: In all, 161 patients were questioned at the end of IMRT and at 12 and 24 months follow-up using the questionnaires of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-30 and QLQ-HN35. Patients' QoL 2 years after IMRT was compared to a population reference sample and QoL of patients from lower, middle, and higher social class 2 years after IMRT was analyzed by ANCOVA using baseline QoL (end of radiation treatment) as a covariate. RESULTS: Patients with high SES report worse QoL at the end of IMRT in the domains global health status (-15.2; p = 0.005), role function (-23.8; p = 0.002), and social function (-19.4; p = 0.023) compared to patients with middle and low SES. QoL improved during the first 12 and 24 months. However, 2 years after IMRT, middle and low SES patients report lower QoL in the domains global health status, physical function, and role function, and report a higher general (fatigue, pain, dyspnea) and head and neck cancer-specific symptom burden (pain, swallowing, senses, speech, social eating, opening mouth, and felt ill) than patients with high SES. CONCLUSION: After IMRT for LAHNC, patients with high SES report worse QoL compared to patients with middle or low SES. There is a marked improvement within the first 24 months in many domains. However, the magnitude of improvement in patients with middle or low SES is significantly smaller compared to patients with high SES.

Current studies of immunotherapy in head and neck cancer.

BACKGROUND: Recently, enormous progress in cancer therapy has been achieved by the use of immune checkpoint inhibitors. Activating the body's own immune system has added a novel and powerful therapeutic option for the treatment of melanoma and lung cancer. Furthermore, the potential use of immunotherapy is being extensively explored also in other malignancies. OBJECTIVE OF REVIEW: This review summarises current clinical studies using immune checkpoint modulators for the treatment of head and neck cancer (HNSCC). TYPE OF REVIEW: Systematic review. SEARCH STRATEGY: A PubMed search from 2010 onwards was performed for the use of immune checkpoint inhibitors in clinical trials of HNSCC. An equivalent search was performed at clinicaltrials.gov. Additionally, the abstracts from the annual meetings of the ASCO, ESMO and AACR were screened. RESULTS: A total of 45 relevant studies using immune checkpoint inhibitors in HNSCC were identified. In the majority of these studies, antagonistic antibodies targeting the immune checkpoint receptors PD-1 are used either solely or combined, mostly with other immunomodulatory antibodies, such as inhibitors of CTLA-4. Most studies are still recruiting patients (26/45). In the primary setting, we identified 16 studies using checkpoint inhibition as neoadjuvant/adjuvant modality for treatment with curative intent. The response rate upon treatment with PD-1 antagonists in relation to the PD-L1 status is being investigated in 12 trials. Novel immune checkpoint modulators combined with the inhibition of the PD-1/PD-L1 axis or CTLA-4 have been set up in six trials. So far, only four studies that use immune checkpoint inhibition in HNSCC have presented results and all of these explored the inhibition of the PD-1/PD-L1 axis. The studies demonstrated overall response rates (ORR) in the range of 20%. These preliminary data suggest that a PD-L1 expression ≥1% is associated with a higher response rate compared to a PD-L1 expression ≤1%. The anti-PD-1-antibody pembrolizumab extended the duration of response in recurrent and/or metastatic (R/M) HNSCC (by approximately 53 weeks) in a phase Ib study. Therefore, pembrolizumab was granted accelerated approval for the treatment of platinum refractory R/M HNSCC by the FDA. CONCLUSION: Numerous clinical trials are addressing the suitability and efficacy of immune checkpoint modulators in HNSCC with the predominant targets being the established immune checkpoint receptors PD-1/PD-L1 and CTLA-4. Recently, presented results have shown a survival benefit, a favourable safety profile and an extended duration of response in favour of using immune checkpoint modulation in R/M HNSCC.

[Treatment of head and neck squamous cell carcinoma recurrences and distant metastases : Highlights of the ASCO Meeting 2016]. / Therapie der rezidivierten und fernmetastasierten Kopf-Hals-Tumoren : Highlights des ASCO-Meetings 2016.

This year particularly phase II studies were presented at the 2016 ASCO Annual Meeting, in which new drugs (monoclonal antibodies, small molecules) were investigated in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC). Notably, there was a great number of studies investigating carcinoma of the nasopharynx. The studies presented in this article summarize the different therapeutic concepts in the treatment of R/M-HNSCC and represent the variety of therapeutic approaches in the recurrent and metastatic setting.

[Immunotherapeutic studies of head and neck tumors : Highlights of the 2016 ASCO Annual Meeting]. / Immuntherapeutische Studien bei Kopf-Hals-Tumoren : Highlights der ASCO-Jahrestagung 2016.

Immunotherapeutic drugs in the form of novel immune checkpoint inhibitors have had a significant impact on and revival of the treatment standards for head and neck tumors. Recently, at the annual meeting of the American Society of Clinical Oncology (ASCO) several innovative immunotherapies in head and neck cancer were presented, which might lead to a paradigm shift in the palliative as well as curative setting in the near future.The most common approaches are antibodies targeting the programmed cell death 1 (PD-1) axis. These therapies seem to be effective in a significant proportion of patients (independent of human papillomavirus) and show an extended duration of response.In a phase III trial for palliative second-line therapy, the PD-1 antibody nivolumab demonstrated a significant improvement in survival in patients with head and neck squamous cell carcinoma (HNSCC) who were experiencing disease progression after platinum-based therapy; therefore, the Food and Drug Administration gave it a breakthrough therapy designation.Further clinical trials focusing on first-line palliative treatment (compared with the EXTREME protocol) as well as neoadjuvant therapies using immune checkpoint-inhibitors are ongoing. However, valid testing systems (e. g., PD-L1 testing) as well as reliable predictive markers for patient selection are necessary to avoid increasing public health costs and to protect patients from potentially serious adverse events.

[Study results of primary therapy for head and neck tumors : Highlights of the 2016 ASCO Annual Meeting]. / Studienergebnisse zur Primärtherapie von Kopf-Hals-Tumoren : Highlights der ASCO-Jahrestagung 2016.

At the annual meeting of the American Society of Clinical Oncology (ASCO) 2016, results of current trials dealing with primary therapy for head and neck squamous cell carcinoma (HNSCC) were presented. Current trials investigate in particular therapy regimens for the treatment of locally advanced HNSCC. Concomitant chemoradiotherapy (CRT) remains the standard therapy approach. Current trials focus on sequential chemoradiation with modifications in induction chemotherapy (ICT) or the subsequent CRT schedule. Studies investigating the combination of targeted therapy with the epidermal growth factor receptor (EGFR) antibody cetuximab and concomitant, sequential, or adjuvant therapy were presented. The most important trials are summarized in this article.

[Immunotherapy for HNSCC : Quo vadis?]. / Immuntherapie des HNSCC : Quo vadis?

BACKGROUND: Immunotherapy remains a hot topic with an endless stream of new upcoming clinical trials. The results of studies to date are promising for second-line palliative treatment of head and neck squamous cell carcinoma (HNSCC). The next step is testing these strategies in randomized trials for first-line and curative treatment in an adjuvant, neoadjuvant, and primarily nonsurgical setting. So far, established biomarkers have not proven reliable enough to predict response rates precisely. OBJECTIVES: On occasion of the annual meeting of the American Society of Clinical Oncology (ASCO), we aimed to invesitage the future of immunotherapies. METHODS: We collected the most promising upcoming studies alongside current research in the field of biomarkers with a  view to interesting new immunotherapeutic strategies. RESULTS: The search for appropriate biomarkers in particular seems to be a central research objective in the short term. There is a broad range of new agents that will be tested in clinical trials as well as the combination of immunotherapy with chemo- and chemoradiotherapy or other immune-modulating drugs. CONCLUSION: The real challenge will be to find the most fitting therapy for each patient out of a large panel of available regimens. Therefore, it is most important to find a set of reliable biomarkers that together could predict treatment response.

Curative treatment of head and neck squamous cell carcinoma : Organ preservation strategies in clinical routine in German-speaking countries.

INTRODUCTION: For the treatment of head and neck squamous cell carcinoma (HNSCC), there are currently no official standard of care guidelines in German-speaking countries, with the exception of oral cavity cancer. In order to learn about the applied treatment modalities in the clinical routine, we conducted a web-based survey to evaluate the local standards of palliative and curative treatment of HNSCC. This article focuses on the curative treatment options and organ preservation strategies. MATERIALS AND METHODS: The survey consisted of a web-based questionnaire that was performed between November 2013 and July 2014. The questionnaire included ten multiple-choice questions and four open questions in the section about curative treatment. RESULTS: Altogether, 62 of the 204 addressed centers participated in the survey. For primary chemoradiation (CRT), most centers used a platinum-based chemotherapy (52/54, 96.3 %). Induction chemotherapy (ICT) was offered in 37 of the 62 centers (60 %). In oral cavity cancer, CRT and ICT were used in 37.5 and 4.3 % of the cases, respectively. In oropharyngeal cancer, CRT and ICT were applied in 44.5 and 10.3 % of cases, respectively. For hypopharyngeal cancer, 44.8 % of the patients received CRT and 11.8 % received ICT, while for laryngeal cancer 35.9 % received CRT and 9.4 % underwent ICT. CONCLUSION: Our data showed that a variety of treatments are used for HNSCC within German-speaking countries. Many centers offer ICT. The majority of the hospitals uses platinum-based therapy as a conservative first-line option in their organ preservation protocols.

Palliative treatment standards for head and neck squamous cell carcinoma : Survey of clinical routine in German-speaking countries.

BACKGROUND: The EXTREME (Erbitux in First-Line Treatment of Recurrent and Metastatic Head and Neck Squamous Cell Carcinoma) protocol is generally considered the gold standard in palliative first-line treatment. However, there is some disagreement about its effectivity, toxicity, and applicability in daily clinical routine. The purpose of this cross-sectional survey was to describe the palliative treatment offered in German-speaking countries. METHODS: From November 2013 to July 2014, 204 departments of otorhinolaryngology (ORL) in Germany, Austria, and the German-speaking parts of Switzerland were contacted and invited to take part in a web-based survey on the treatment of HNSCC. RESULTS: In all, 62 of 204 treatment centers (30.4 %) participated in the survey. Of these, 58 departments offered palliative systemic therapy to their patients; 19 of 58 (32.8 %) treated patients undergoing palliative chemotherapy in their own ORL departments, while 40 of 58 (69 %) upheld a cooperation with medical oncologists in the same hospital and 24 of 58 (41.4 %) with medical oncologic practices. Many of these treatment centers offered multiple locations for treatment. Of the 58 departments, 56 provided an institutional standard for first-line palliative treatment, 13 for second-line, and two for third-line treatment. In 42 of 58 departments the EXTREME protocol was the institutional standard of care for first-line treatment. Moreover, 12 of 58 departments mentioned an individual protocol and two of 58 the inclusion in clinical trials as their local standard. The assessment of patients who could be treated with the first-line standard ranged from 0 to 95 % with a mean of 44.5 %. CONCLUSION: Palliative systemic therapy seems to be well standardized for first-line treatment, whereas there is little standardization in second- and third-line treatments. A large variation was found regarding the estimate of the applicability of the institutional standard. Reasons for this could be the physicians' individual experience as well as the varying assessment regarding the toxicity of palliative systemic therapy.

Malondialdehyde Epitopes as Targets of Immunity and the Implications for Atherosclerosis.

Accumulating evidence suggests that oxidation-specific epitopes (OSEs) constitute a novel class of damage-associated molecular patterns (DAMPs) generated during high oxidative stress but also in the physiological process of apoptosis. To deal with the potentially harmful consequences of such epitopes, the immune system has developed several mechanisms to protect from OSEs and to orchestrate their clearance, including IgM natural antibodies and both cellular- and membrane-bound receptors. Here, we focus on malondialdehyde (MDA) epitopes as prominent examples of OSEs that trigger both innate and adaptive immune responses. First, we review the mechanisms of MDA generation, the different types of adducts on various biomolecules and provide relevant examples for physiological carriers of MDA such as apoptotic cells, microvesicles, or oxidized low-density lipoproteins. Based on recent insights, we argue that MDA epitopes contribute to the maintenance of homeostatic functions by acting as markers of elevated oxidative stress and tissue damage. We discuss multiple lines of evidence that MDA epitopes are proinflammatory and thus important targets of innate and adaptive immune responses. Finally, we illustrate the relevance of MDA epitopes in human pathologies by describing their capacity to drive inflammatory processes in atherosclerosis and highlighting protective mechanisms of immunity that could be exploited for therapeutic purposes.

Postoperative antibiotic prophylaxis in clean-contaminated head and neck oncologic surgery: a retrospective cohort study.

Antibiotic prophylaxis is commonly used in head and neck oncologic surgery, due to the clean-contaminated nature of these procedures. There is a wide variety in the use of prophylactic antibiotics regarding the duration of application and the choice of agent. The purpose of this study was to determine whether short-term or long-term antibiotic prophylaxis has an impact on the development of head and neck surgical wound infection (SWI). Retrospective chart review was carried out in 418 clean-contaminated head and neck surgical oncology cases at our department. More than 50 variables including tumour type and stage, type of surgical treatment, co-morbidities, duration and choice of antibiotic prophylaxis, and the incidence of SWI were analysed. Following descriptive data analysis, Chi square test by Pearson and Fisher's exact test were used for statistical evaluation. Fifty-eight of the 418 patients (13.9 %) developed SWI. Patients with advanced disease and tracheotomy showed a significantly higher rate of SWI than those with early stage disease and without tracheotomy (p = 0.012 and p = 0.00017, respectively). However, there was no significant difference between the SWI rates in the short term and long term treatment groups (14.6 and 13.2 %, respectively; p = 0.689). Diabetes and body weight were not found to be risk factors for SWI. Long-term antibiotic prophylaxis was not associated with a decrease in SWI in the entire cohort of patients undergoing clean-contaminated major head and neck oncologic surgery. Our data confirmed the extent of surgery and tracheotomy as being risk factors for postoperative SWI.