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In this open uncontrolled phase I study, nine patients with stage III and IV squamous cell carcinoma of the head and neck (SCCHN) were treated with five administrations of the humanized antiepidermal growth factor receptor monoclonal antibody EMD 72000 in three consecutive ascending dose groups. Loading doses of 100 mg (group I), 200 mg (group II), and 400 mg (group III) were followed by four weekly maintenance doses of half the loading doses, i.e. 50, 100, and 200 mg, respectively. Two EMD 72000 administrations were scheduled before and three after surgery. The objectives of this trial were (a) to investigate the safety and toxicity of multiple EMD 72000 doses, (b) to determine the cumulative maximum tolerated dose of EMD 72000 at dosages between 300 mg and 1,200 mg, and (c) to determine the serum pharmacokinetics of EMD 72000. In total, 102 adverse events (AEs) were reported: five of toxicity grade 3, 18 of toxicity grade 2, 66 of toxicity grade 1, and 38 of toxicity grade 0. All AEs of toxicity grade 3 were considered to be not or remotely related to EMD 72000. The most frequent study drug-related AEs were fever and a transient elevation of liver enzymes. In all patients, the time to reach peak serum concentrations (tmax) was within 1-3 h of the start of each EMD 72000 infusion. Average peak serum concentrations (Cmax) after correction for dosage appeared to be dose-independent, whereas the half-life (t1/2) showed dose dependency. In conclusion, EMD 72000 was very well tolerated in patients with advanced stage SCCHN. The pharmacokinetic data from this trial suggest the feasibility of conducting future studies with weekly doses of 200 mg EMD 72000. [ABSTRACT FROM AUTHOR]

In 59 cases of primary human renal cell carcinoma (RCC), cross-resistance and collateral susceptibility patterns were determined in an MTT microculture assay. Concomitantly, the glutathione (GSH) content and the enzymatic activity of γ-glutamyl transpeptidase (GGT) were measured as distinct resistance characteristics. Resistance or chemoresponse towards Vinca alkaloids and anthracyclines were found to be highly coincident, suggesting that the classical multidrug resistance mechanism is active in human RCC. Strong resistance to platinum complexes combined with relative sensitivity to bleomycin was significantly associated with elevated glutathione levels, providing evidence for another pathway instigating chemoresistance. In contrast, despite substantial enzymatic activity, GGT effects revealed no correlation to the chemoresistance pattern. This result implies that it is the GSH-linked binding and reduction potential rather than the GGT-associated transportation capacity that has an impact on the expression of chemoresistance in human RCC. [ABSTRACT FROM AUTHOR]

The murine IgG2a monoclonal antibody (mAb) EMD 55900 was produced against the human epidermoid carcinoma cell line A431, with binding occurring to the polypeptide chain of the external domain of human epidermal growth factor receptor (EGF-R). In the present clinical study, 12 patients with advanced squamous cell carcinoma of the larynx or hypopharynx received a single dose of either 20, 100 or 400 mg EMD 55900 3 days prior to laryngectomy and neck dissection. Clinical signs and laboratory parameters of toxicity, development of human anti-mouse antibodies, and mAb plasma concentrations were monitored. In tumor specimens studied from primary tumors and lymph node metastases, expression of EGF-R, distribution of EMD 55900, and occupation of EGF-R by EMD 55900 (double staining) were determined by immunohistochemistry. Single-dose administration of EMD 55900 was very well tolerated in all patients, and good (100 mg) to excellent (400 mg) homogeneous binding of mAb to EGF-R was obtained in the advanced laryngeal and hypopharyngeal carcinomas studied. [ABSTRACT FROM AUTHOR]

Since in vitro derived tumor cell lines usually correspond to their tumors of origin, a potential biological difference between a primary tumor and its derivative metastases and recurrent tumors should be reflected in established tumor cell lines. The aim of this study was to determine useful cellular markers in permanent tumor cell lines of head and neck squamous cell carcinomas (SCC) and to evaluate a possible relationship between these markers and the origin of selected cell lines. The cell lines, established in the laboratory of T. Carey at the University of Michigan (UM) (Ann Arbor, Mich., USA), were derived from primary tumor and its metastases (UM-SCC 10A, IOB), primary tumor and its recurrent tumors (UM-SCC 14A, 14B, 14C) and single tumors (UM-SCC 11B, 17A, 22B). An additional tumor cell line (HLac 79) was isolated by H.-P. Zenner (Tübingen, Germany) and a clone (8029 NA) with its cisplatin-resistant subline (8029 DDP4) was established in our laboratory. As markers we chose three groups known to be related to growth behavior and/or tumor differentiation: cytoskeletal proteins, oncogene products and membrane-associated antigens. These markers were detected by immunohistochemical methods using commercially available monoclonal antibodies. The 'metastatic' and 'recurrent' cell lines showed changes in comparison to the corresponding 'parental' lines, which could be associated with a higher degree of de-differentiation, such as the occurrence of vimentin and neuroectodermal proteins, loss of HLA-ABC or HLA-DR and increased expression of epidermal growth factor receptor. The expression of cytokeratins was more stable and dissociation of the classical cytokeratin pairs was observed only in a few cases. Oncogene products were practically identical in cell lines from parental and recurrent or metastatic tumors. These data serve not only as a basis for further experiments with these cell lines but also provide information about the biological significance of various markers in newly established cell lines from primary tumors. [ABSTRACT FROM AUTHOR]

Considerable progress has been made in the development of more effective chemotherapy regimens for squamous cell head and neck carcinomas. Unfortunately, increased response rates have not been translated into marked improvements in survival since durations of response have been brief, and the natural history of the disease has ultimately remained unaltered. Since the development of drug resistance is a major obstacle to successful antineoplastic chemotherapy, comprehensive efforts have been focused on understanding the underlying mechanisms. In this review, general and specific aspects of drug resistance related to head and neck cancer are addressed. In particular, mechanisms of resistance towards the most widely used antineoplastic drugs in head and neck malignancies - methothrexate, cisplatin, 5-fluorouracil, bleomycin, and vincristine - are discussed. [ABSTRACT FROM AUTHOR]

Malignancy is the result of multistep transformational changes of normal somatic cells. In the case of respiratory epithelial malignancies this process lasts for several years. Many methods have been explored to mimic this process in an extracorporal model. In the present investigation we combined several of these methods. Organ cultures were prepared from tracheal specimens and were then consecutively treated with human papilloma virus, benzo(a)pyrene, methylnitronitrosoguanine and tetradecanoyl phorbol acetate. Identical numbers of organ cultures from the same specimen were maintained without exposure to carcinogens. After 6 weeks these cultures were further cultivated either in mixed cultures (MC) with autologous isotopic fibroblasts or under the kidney capsule of the nude mouse (SRC). These two methods were combined after a few months: MC cells were transplanted under the SRC or SRC transplants were explanted in cell culture. This long-term selection procedure revealed striking differences between control and treated organ cultures. Three-dimensional structures containing epithelial cells were isolated from both organ cultures but survived more than 3 months only from treated cultures. Only MC from treated organ cultures produced nodules under SRC. The incidence and morphology of the nodules in the SRC were directly related to carcinogen treatment, with more nodules with pronounced epithelial cell atypia obtained from treated organ cultures. MC and SRC showed the importance of a time factor for selecting cells with changed growth behavior -increased time increased the incidence of such cells. [ABSTRACT FROM AUTHOR]

The article features icatibant in the pharmacotheraphy of acute hereditary angioedema (HAE). Icatibant is a selective bradykinin B2-receptor antagonist, effective in treating HAE. Acute attacks of HAE are often treated with oral tranexamic acid and administered by C1-esterase inhibitor. Information on a patient with HAE type 1, experienced several recurrent angiodema attacks and treated with icatibant is provided.

This study was designed to identify new factors which may contribute to angiotensin-converting-enzyme-inhibitor (ACEI)-induced angioedema.In a retrospective cohort study we examined 25 patients who used an ACEI and presented at our emergency room with acute angioedema as well as 18 patients with unknown cause of angioedema and a total of 21 patients on ACEI-therapy without previous angioedema. We measured markers of inflammation such as acute-phase proteins (C-reactive protein, fibrinogen), leukocyte count and body temperature.The mean interval between initiation of ACEI treatment and first manifestation of angioedema was 35.8 ± 5.3 months. During symptomatic angioedema, mean plasma levels of C-reactive protein and fibrinogen were significantly increased by 7.3-fold and 1.5-fold, respectively, while leukocyte count and body temperature were normal. These changes disappeared after successful treatment of angioedema and were not found in patients with angioedema of unknown cause and those receiving ACEI without having experienced angioedema.Our findings demonstrate for the first time that ACEI-induced angioedema is associated with strongly increased plasma levels of CRP. We suggest that CRP is involved in the pathophysiology of ACEI-induced angioedema. [ABSTRACT FROM AUTHOR]

Objective: This retrospective multicenter study aimed to evaluate surgical versus conservative treatment in patients with hypopharyngeal and laryngeal cancer under real world conditions., Methods: This study included 2307 patients diagnosed with hypopharyngeal or laryngeal squamous cell carcinoma (SCC) in five German tertiary head and neck centers between 01/2004 and 12/2014. Overall, 783 patients with advanced SCC consecutively underwent laryng(opharyng)ectomy (L(P)E). Patient chart data regarding age, sex, tumor location, TNM status, grading, indication for L(P)E, treatment modalities, R status, postoperative complications, and hospitalization time were analyzed. Patients with lacking data and incomplete staging and those who refused treatment or did not comply with the recommended treatment were excluded from survival analysis., Results: A slight but significant increase was observed in L(P)E, referring to an increasing rate of tumor recurrence. While T1/2N0M0 laryngeal and hypopharyngeal cancer patients showed comparable overall survival (OS) for surgical and conservative treatment, surgery showed significantly better OS in lymph node-positive individuals and locally advanced tumor stages. Tumor recurrence occurred in more than one-third of the cases. In particular, in early glottic cancer recurrence, L(P)E represents a curative and safe treatment option, whereas in supraglottic and hypopharyngeal cancer, L(P)E was associated with reduced survival rates. Notably, 36% of patients with supraglottic cancer and 59% of patients with hypopharyngeal cancer recurrence could only be treated with palliative care., Conclusion: Comparable survival rates were demonstrated for cT1/2N0M0 laryngeal and hypopharyngeal SCC compared with primary chemo-/radiotherapy and larynx-preserving surgery. Better OS was achieved after surgery in nodal-positive patients and in those with locally advanced disease. Tumor recurrence should be anticipated in up to 39% of cases. Glottic cancer recurrence can be successfully and safely treated with L(P)E, whereas OS is reduced in hypopharyngeal cancer and possibly in supraglottic cancer., (© 2024. The Author(s).)

Background: Diagnosis of pollen allergies is mainly based on test allergens for skin prick testing. In the minimum battery of test inhalant allergens recommended by the Global Allergy and Asthma European Network 10 pollen allergens are included. Complementary other pollen allergens may need to be considered; however, respective awareness may not always be granted. Furthermore, at least in Germany, the situation may be even more complicated by the fact that test allergens need regulatory approval. A decline in commercially available test allergens may result in a diagnostic gap regarding patients with non-frequent allergies. How many patients with non-frequent pollen allergies would be affected by this gap? The data presented here partly answer this question., Methods: The study consisted of a descriptive and an analytical part. In the descriptive part, sensitization to frequent pollen allergens (alder, hazel, birch, sweet grasses; according to the German Therapy Allergen Ordinance) and to respective non-frequent pollen allergens (cypress, Japanese cedar, ash, plane tree, olive, Bermuda grass, wall pellitory, plantain, goosefoot, mugwort, ragweed, and saltwort) was measured in adult patients with physician-diagnosed allergic rhinitis from two German federal states, namely North-Rhine Westphalia ( n  = 360) and Bavaria ( n  = 339), using skin prick testing and/or ISAC technology. Furthermore, respective regional pollen data were assessed. In the analytical part, sensitization data were correlated with each other and with anamnestic data on symptom periods., Results: Sensitization to frequent pollen allergens ranged from 45% (sIgE to Aln g 1/Alder, NRW) to 72% (prick test reactivity to birch, NRW). Sensitization to non-frequent pollen allergens ranged from 0% (sIgE to Amb a 1/ragweed, NRW) to 41% (prick test reactivity to olive, Bavaria). Sensitization data partly correlated with each other and in connection with symptom periods showed a partly similar seasonal pattern as pollen data., Conclusions: Sensitization to non-frequent pollen allergens have to be considered when examining patients with respective seasonal symptoms, and test (and respective therapy) allergens for non-frequent pollen allergies need to be available. Further prerequisites for adequate patient management would be a nationwide pollen monitoring system giving continuous pollen data and a systematic sensitization monitoring at patient level., Competing Interests: The authors declare that they have no competing interests., (© 2021 The Authors. Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.)

Objective: The aim of this study was to assess the functional outcome after transmandibular resection and reconstruction via a radial forearm flap (TMR+RFF) compared to primary chemoradiotherapy (pCRT) in advanced oropharyngeal squamous cell carcinoma (OPSCC)., Methods: The study compared 50 OPSCC patients treated with TMR+RFF to 50 OPSCC patients receiving pCRT. The time taken to swallow water served as the primary endpoint. The Saxon test, maxillomandibular distance, Mallampati score, ratio of height to weight, nasal penetration, tracheostomy/gastral tube requirement, and four validated questionnaires (visual analog scale for xerostomia, Sicca VAS; MD Anderson Dysphagia Inventory, MDADI; Voice Handicap Index, VHI; European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Head and Neck Cancer, 35 items, QLQ-H&N35) were applied to access functionality and quality of life., Results: Patients after TMR+RFF showed an increased rate of nasal penetration (p < 0.0001), which was associated with a longer water swallowing time (p < 0.05). A modified reconstruction of the soft palate significantly decreased the rate of nasal penetration in comparison to classical reconstruction (p = 0.0001). Patients with pCRT suffered significantly more xerostomia (Saxon test) than patients with TMR+RFF and adjuvant therapy. None of the subjective questionnaires revealed significant differences between the groups., Conclusion: TMR+RFF with modified reconstruction and adjuvant treatment and pCRT showed comparable functional outcomes.

Background: To access the influence of insurance status on time of diagnosis, quality of treatment and survival in head and neck squamous cell carcinoma (HNSCC)., Methods: This mono-institutional retrospective cohort analysis included all HNSCC patients (n = 1,054) treated between 2001 and 2011, and subdivided the cohort according to the insurance status. Differences between the groups were analyzed using the Chi square and the unpaired student's t-test. Survival rates were calculated by Kaplan-Meier and Cox regression for forward selection., Results: Nine hundred twenty-five patients showed general, 129 private insurance. The 2 groups were equal regarding age, gender, tumor localization, therapy, and N/M/G/R-status. The T-status differed significantly between the groups showing more advanced tumors in patients with general insurance (p = 0.002). While recurrence-free survival was comparable in both groups, overall survival was significantly better in private patients (p = 0.009). The time frame between first symptom and diagnosis was equal in both groups., Conclusions: The time frame between subjective percipience of first symptom and final therapy did not differ between the groups. In our cohort, access to otorhinolaryngological specialists is favorable in both, patients with general and private insurance. Recurrence-free survival was comparable in both groups, indicating successful HNSCC treatment both groups. However, overall survival was significantly better in patients with private insurance suggesting other socioeconomic factors influencing survival.

Objective: Contralateral elective neck dissection (cEND) in oral and oropharyngeal squamous cell cancer (OC/OPC) is still a matter of debate. The current study analyzed the outcome in OC/OPC patients with/without cEND., Methods: OC/OPC patients (n = 471) were diagnosed with contralateral N0 after CT/MRI-scan combined with neck ultrasound. Clinico-pathological features were analyzed using Chi-square/Fisher exact/Student's t test. Survival rates were calculated using Kaplan-Meier and log-rank test. Prognostic variables were evaluated by Cox regression. Primary/secondary endpoints were overall/recurrence-free survival (OS/RFS)., Results: Pre-therapeutic imaging revealed a significantly over-staged N-status (p = 0.01), while occult contra-lateral N + was diagnosed in one patient only (0.4%). OC patients did not show differences in OS/RFS between the groups (ipsi- vs. bi-lateral). There was a strong tendency towards a better OS in OPC patients who underwent ipsi-lateral ND (p = 0.07). Cox-regression demonstrated that only tumor recurrence was associated with a fivefold increased risk of recurrence-associated death (p < 0.0001) that referred to a significant higher recurrence rate at primary tumor site (rT +) and increased distant metastatic outgrowth in OPC who underwent bi-lateral neck dissection (p = 0.03). While RFS of any cause (rT + /rN + /rM +) was significantly better in OPC with ipsi-lateral ND (p < 0.05), RFS of contralateral lymph node recurrence (rN2c) was comparable in both groups., Conclusion: END of the contralateral cN0 neck is not correlated by an increased RFS or OS. Standard imaging techniques including CT/MRI scan and neck ultrasound warrant watchful waiting for neck dissection of the contralateral cN0 neck.

Purpose: The concept of dysphagia/aspiration-related structures (DARS) was developed against the background of severe late side effects of radiotherapy (RT) for head and neck cancer (HNC). DARS can be delineated on CT scans, but with a better morphological discrimination on magnetic resonance imaging (MRI). Swallowing function was analyzed by use of patient charts and prospective investigations and questionnaires., Method: Seventeen HNC patients treated with intensity-modulated radiotherapy (IMRT) ± chemotherapy between 5/2012 - 8/2015 were included. Planning CT (computed tomography) scans and MRIs (magnetic resonance imaging) prior, during 40 Gray (Gy) radiotherapy and posttreatment were available and co-registered to delineate DARS. The RT dose of each DARS was calculated. Five patients were investigated posttreatment for swallowing function and assessed by means of various questionnaires for quality of life (QoL), swallowing, and voice function., Results: By retrospective comparison of DARS volume, a significant change in four of eight DARS was detected over time. Three increased and one diminished. The risk of posttreatment dysphagia rose by every 1Gy above the mean dose (D mean) of RT to DARS. 7.5 was the risk factor for dysphagia in the first 6 months, reducing to 4.7 for months 6-12 posttreatment. For all five patients of the prospective part of swallowing investigations, a function disturbance was detected. These results were in contrast to the self-assessment of patients by questionnaires. There was neither a dose dependency of D mean DARS volume changes over time nor of dysphonia and no correlation between volume changes, dysphagia or dysphonia., Conclusion: Delineation of DARS on MRI co-registered to planning CT gave the opportunity to differentiate morphology better than by CT alone. Due to the small number of patients with complete MRI scans over time, we failed to detect a dose dependency of DARS and swallowing and voice disorder posttreatment., Competing Interests: The authors have declared that no competing interests exist.

Specific IgE measurements obtained from patients suffering from respiratory allergy (n = 952) show that, despite similar climatic conditions, there are clear regional differences in pollen sensitization between North Rhine-Westphalia and Bavaria. The data on sensitization levels and pollen concentration was taken from the research and development project Ufoplan 3710 61 228 of the German Environment Agency for North Rhine-Westphalia and Bavaria (2011 - 2014). Most poly-sensitized patients have already shown sensitization, both in the form of cross-reactivity and species-specific sensitization, to "new" pollen allergens, such as Bermuda grass and olive tree. These plants are currently not common in Germany, but may become considerably more widespread due to the increase in average yearly temperatures caused by the global warming. The other "new" aeroallergens discussed here are plants that can be found throughout Germany, such as nettle, cypress, and pine. Their current sensitization levels are higher than 8%; however, their clinical impact appears to be underestimated. For clinical practice it is important to identify when patients' symptoms are typically severe and which regional plants might be responsible for the patients' complaints in this period of time, as this affects further diagnostic strategy. Allergens having an immune effect can then be targeted by specific immunotherapies. The information on complaints of the patients should be regularly recorded in symptom diaries. Recording this information for at least 1 year may allow to discover a correlation between specific types of pollen and allergy symptoms., (© Dustri-Verlag Dr. K. Feistle.)

Background: Carotid blowout syndrome (CBS) is a rare but life-threatening complication of head and neck squamous cell carcinoma (HNSCC). Chemoradiation (CRT) may make CBS more likely, but so far no longitudinal analysis of different treatment strategies has been conducted., Methods: In the present study, 1072 patients with HNSCC were divided into groups depending on whether they had experienced CBS. Disease-related data were analyzed using chi-square test, Fisher exact test, and Student's t test. Survival rates were calculated using Kaplan-Meier test, log-rank test, and the Cox regression analysis for forward selection., Results: Thirty-six patients suffering from CBS demonstrated significantly advanced T status (P = .001) and UICC stage (P = .004) when compared with unaltered counterparts. After adjustment for UICC stage, OS was comparable in both groups, whereas the mean recurrence-free survival (RFS) rate was better in unaltered patients (67 vs 24 months; P < .0001). Cox regression for forward selection revealed local recurrence (hazard ratio [HR], 1.9; P < .0001), T status (HR, 1.9; P = .03), and CRT (HR, 2.0; P < .0001) as independent risk factors for mortality related to CBS., Conclusion: CBS is a rare event in patients with HNSCC demonstrating reduced OS/RFS. Advanced T status, C/RT, and the recurrence of local tumors increase the risk of CBS-associated death., (© 2019 Wiley Periodicals, Inc.)

Introduction: Prospective clinical trials are essential to translate new therapy concepts or rather any scientific development into the medical routine. Besides a sophisticated trial protocol, the success of clinical trials depends on patient recruitment and participation. Patient recruitment remains a challenge and depends on several factors. To get a current picture of the patients' attitude, we conducted the present survey., Methods: We designed a survey with seven questions, which was given to all oncological patients treated within a timeframe of three months between Mai and July 2017. Participation was voluntary and anonymous. The questionnaire mainly inquires patients' participation in clinical trials in a university-based setting, their attitude towards clinical trials regarding risks and benefits, and their source of information in this context., Results: 771 patients (1:1 male/female) participated with a median age of 61 years (range 18-91 years) with a response rate of 71.5%. Of all, 17.8% (137/771) were participating in a clinical trial. The most mentioned reason was to serve medical progress and cancer research. Out of the patients not currently participating in a trial, 79 (12.7%, 79/623) refusers named the following main reasons: extensive travel time to the clinic, no therapeutic advantage, and too time-consuming. Out of the patients not offered to take part in a trial, 265 (51.0%, 265/520) would participate if offered. Of all patients, 8.3% (64/771) used the clinics' homepage as a source of information, of those 79.7% (51/64) were satisfied with its content. To enhance patient recruitment strategies, we asked how patients wish to be informed about possible trials: More than half (52.0%) of the questioned patients preferred an individual medical consultation with their physician.We further analyzed the trial participation depending on age, gender, unit, and tumor entity. We could show a significant influence of age (p < 0.001) but not for gender (p = 0.724). The trial participation was also significantly associated with the treating unit (p < 0.001) and tumor entity (p = 0.001)., Conclusion: Patients are willing to participate in clinical trials. Better information strategies need to be implemented. Physicians need to be aware of running trials within their department and must counseling counsel patients effectively to improve recruitment. Trial concepts should keep in mind patients' needs including an adequate number of appointments, positive risk-benefit profiles, and information material.

Background: Head and Neck Surgery constantly has to oppose non-invasive organ preservation methods and therefore should be evaluated especially with regard to clinical and functional outcome. We will discuss the role of pharyngotomy in the treatment of HNSCC., Methods: Seventy-three patients with carcinoma of the oral cavity, oro-/hypopharynx and supraglottis underwent lateral/median pharyngotomy. Functional and oncological parameters were retrospectively assessed and set into clinical context., Results: The 5-year recurrence-free-interval (RFI) was significantly higher with surgery and adjuvant radio(chemo)therapy (80%; mean RFI: 92 months) when compared to conservative treatment (68%; mean RFI: 68 months). The 5-year overall-survival (OS) after surgery and conservative treatment was 71% and 54%, respectively. Compared to other surgical techniques (mean RFI: 82 months), pharyngotomy demonstrated a significant higher 5-year RFI (mean RFI: 89 months)., Conclusions: Pharyngotomy achieves good exposure and clear resection margins that result in a notably good oncological outcome with a minimum of functional loss. In particular, among UICC IV oropharyngeal HNSCC, pharyngotomy is superior in OS and RFI to conservative methods.

Objectives: Despite modern treatment regimens, overall survival in head and neck squamous cell carcinomas (HNSCC) is less than 50% due to local and systemic disease recurrency. The current study aims to identify molecular markers in primary tumor specimens that predict the risk for local and systemic recurrency at the time of initial diagnosis., Methods: The study included clinic-pathological data of 1,057 HNSCC. MMP2/9, TIMP1/2, CXCR4, and CXCL12 immunohistochemistry was done in 150 randomly selected specimens. For statistics, we employed Chi square, Fisher exact, and Student's t-test. Overall survival (OS) was calculated by Kaplan-Meier and log-rank test. Prognostic variables were subsequently evaluated by Cox regression for forward selection., Results: CXCR4 positive specimens demonstrated a significant increased risk for tumor recurrency associated death (rT: HR 10.07; p=0.001 / rN: HR 5.04; p=0.013 / rM: HR 2.49; p=0.029) when compared with their unaltered counterparts. Expression of MMP9, TIMP2, CXCR4, and CXCL12 was significantly increased in distant metastasized patients (p<0.0001) and showed significant cross-correlation. In addition, CXCR4 positivity was associated with an increased risk to die due to enhanced T or N status (T1/2 vs. T3/4: HR 5.78; p=0.017; N0 vs. N+: HR 5.18; p=0.033)., Conclusion: CXCR4 positivity in tumor samples at initial diagnosis were associated with reduced overall survival, in particular with respect to increasing T/N status, local and systemic recurrency., Competing Interests: CONFLICTS OF INTEREST All authors state no conflicts of interest.

Background: Parotid gland surgery (PGS) has to manage the balancing act between sufficient radicality and preservation of functional structures. While many studies evaluate post-therapeutic complication due to different extent of surgery, the current study introduces bipolar dissection (BP) being a fast and safe preparation technique., Methods: Analysis of clinical parameters (age, sex, tumour entity, treatment modalities, facial nerve palsy, bleeding, saliva fistula and Frey's syndrome) of 319 consecutively included patients who underwent extracapsular dissection and superficial/total/radical parotidectomy. Subgroup analysis was done according to the preparation technique (cold vs BP)., Results: Facial nerve palsy rate increased with the extent of PGS (p < .0001). There were no differences in the risk of post-operative bleeding, salivary fistula and Frey's syndrome. BP resulted in a significant reduction of operation time (p = .04), postoperative bleeding (p = .001) and salivary fistula (p = .045) when compared with cold preparation., Conclusions: Ubiquitous available BP allows fast and safe PGS regardless its extent.

Objectives: The resection status is one of the most important prognostic factors for patients with head and neck squamous cell carcinoma (HNSCC) concerning overall survival (OS) and recurrence free interval (RFI). To assess whether therapy concepts changed depending on different resection margins and extracapsular extension, OS and RFI data were set into clinical context., Methods: All HNSCC patients who underwent head and neck surgery with/without adjuvant therapy (n=534) were selected over a ten-year period (2001-2011). Clinical parameters and survival data were collected retrospectively and histopathological analysis of tumor free margins and extracapsular extension were done., Results: Patients with microscopic in-sano resection showed mean OS/RFI of 95/96 months. OS/RFI decreased in microscopic non-in-sano and macroscopic non-in-sano (56/58 and 35/39 months) as well as in unclear resection margins (63/60 months). Patients with extracapsular extension, microscopic non - in-sano resection as well as patients with in-sano resection after follow up resection demonstrated therapy escalation by adjuvant (chemo-) radiation., Conclusions: Insufficient surgical margins and extracapsular extension are main risks for a reduced overall and recurrence free survival. Although there is no measure to prevent positive extracapsular extension, clear margins at first pass protect patients from adjuvant therapy escalation., Competing Interests: CONFLICTS OF INTEREST All authors state no conflicts of interest.