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OBJECTIVE: To analyze postoperative complications after microsurgery for acoustic neuroma (AN) via the middle fossa approach (MFA). MATERIALS and METHODS: In total, 203 consecutive patients of a tertiary skull base referral center at a university hospital were included in this retrospective chart and database analysis. All patients had undergone primary microsurgery at the Otorhinolaryngology department via MFA between December 2005 and October 2014. Postoperative complications were documented during the inpatient stay and outpatient follow-up. RESULTS: Overall, 41 complications were registered in 35 patients. The most common was cerebrospinal fluid (CSF) leakage in 13% of the patients. Bleeding complications were documented in seven patients: two cerebellar bleedings, one subdural and one epidural hematoma, two hematomas of the skin, and one bleeding through the closed wound. Two patients experienced meningitis and one patient had a transient ischemic attack. Furthermore, three cases of deep vein thrombosis occurred, which led to a lethal pulmonary embolism in one case. One patient sustained temporary palsy of the vocal fold and another reported antibiotic-associated diarrhea. CONCLUSION: Acoustic neuroma surgery via the MFA can be conducted with low morbidity and mortality. The most common complication is CSF leakage, which can be treated in most cases in a stepwise conservative manner. Severe adverse events that may require revision surgery are very scarce (1%). [ABSTRACT FROM AUTHOR]

Asthma and allergies are both major global health problems with an increasing prevalence, and environmental data implicate an influence of air pollutants on their development. The present study focuses on the influence of nitrogen dioxide (NO2) and the major allergen of the house dust mite Der p 1 on human nasal epithelial cells of nonallergic patients in vitro. Nasal epithelial mucosa samples of 11 donors were harvested during nasal air passage surgery and cultured as an air-liquid interface. Exposure to 0.1, 1 and 10 ppm NO2 or synthetic air as a control was performed for 1 h. Subsequently, the cells were exposed to Der p 1 for 24 h. The release of interleukin (IL)-6 and IL-8 was measured by ELISA, and the production of IL-6 mRNA and IL-8 mRNA was measured by RT-PCR. NO2 exposure resulted in a concentration-dependent release of IL-6, but not IL-8 release. The coexposure of 0.1 ppm NO2 and Der p 1, or 1 ppm NO2 and Der p 1 significantly increased both IL-6 and IL-8 release. Exposure to NO2, Der p 1, or their combination, did not significantly influence the production of IL-6 or IL-8 mRNA. In conclusion, NO2 in-creases the release of inflammatory cytokines in human nasal epithelial cells, especially in coexposure with Der p 1, as a mechanism of allergotoxicology. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Xerostomia is still one of the predominant side effects of radiotherapy (RT). This study investigates long-term results of a new surgical method that spares the submandibular gland from radiation.Study Design: Eleven patients with head and neck carcinoma were enrolled in the study. In five patients 6-month follow-up testing, and in two of these patients 12-month follow-up testing was performed.Methods: The submandibular gland was transplanted to the patients forearm for the time of radiation. Two months after completion of RT, the gland was retransplanted to the neck. Patients saliva flow was tested via the Saxon test, and patients had to answer the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck 35 and visual analog scale.Results: Following the two-stage autotransplantation, xerostomia was reduced in the long term due to improved saliva production of the reimplanted gland.Conclusions: Whether this promising novel approach is a reliable treatment option for RT patients in general should be evaluated in further studies.Level Of Evidence: 4. Laryngoscope, 126:1551-1555, 2016. [ABSTRACT FROM AUTHOR]

Surgery, radiation, chemotherapy or a combinations of these are all accepted modalities for the treatment of head and neck squamous cell carcinoma (HNSCC). Despite this, 40-60% of patients suffering from HNSCC develop loco-regional failure and/or distant metastases. Salinomycin has been demonstrated to be >100-fold more effective than paclitaxel at causing cancer stem cell death, therefore, it may offer an important improvement in cancer therapy. However, the toxicity of salinomycin is of concern. A possible solution may be the administration of additive drugs, which reduce the toxicity. By inhibiting the mitochondrial Na+/Ca2+ exchanger using the benzodiazepine derivate, CGP37157 (CGP), a significant reduction in salinomycin neuronal toxicity has been observed. This raises the question of whether CGP also inhibits the tumor toxicity of salinomycin. In the present study, the FaDu and HLaC79 C1 HNSCC cell lines were treated with salinomycin with or without CGP. Comparative viability assessments were performed using microscopy, a fluorescein diacetate assay, an MTT assay, a clonogenic assay and annexin V-propidium iodide staining. The expression levels of MDR-1 were monitored using reverse transcription-quantitative polymerase chain reaction. Salinomycin alone, and in combination with CGP, achieved a significant attenuation of cell viability and increased apoptosis in a dose-dependent manner. However, the tumor toxicity of salinomycin was not inhibited by CGP. The HLaC79 C1 cells were more sensitive to salinomycin, compared with the FaDu cells, with this sensitivity being due to high expression levels of MDR-1 by the HLaC79 C1 cells. In conclusion, CGP did not counteract the tumor toxicity of salinomycin in vitro and may be a promising drug in future anticancer therapy. The results of the present study encourages further investigation of the toxicological aspects of salinomycin, particularly in human cells and animal models. [ABSTRACT FROM AUTHOR]

In the discussion on toxic and genotoxic thresholds of air pollutants such as nitrogen dioxide (NO2), realistically low urban concentration ranges are of major interest. For NO2, the WHO defines the annual limit value as corresponding to 0.02 ppm. In the present study, the toxicity and genotoxicity of NO2 is set at a concentration under this limit value and examined in human nasal epithelium at different exposure durations in vitro. Nasal epithelial mucosa samples of 10 donors were harvested during nasal air passage surgery and cultured as an air-liquid interface. Exposure to 0.01 ppm NO2 or synthetic air as a control was performed for 0.5, 1, 2 and 3 h. Analysis included the caspase-3 ELISA, the single cell microgel electrophoresis (comet) assay and the micronucleus assay. The caspase-3 activity was not influenced by NO2 exposure, DNA strand fragmentation correlated with exposure durations to NO2 at 0.01 ppm NO2, and no cytotoxic effects such as apoptosis, necrosis or disturbances of cell proliferation were present. However, micronucleus induction as a sign of genotoxicity at an exposure duration of 3 h could be shown. Shorter exposures did not induce micronucleus formation. In summary, genotoxicity of NO2 could be demonstrated at a common urban concentration in vitro, but a threshold of NO2 genotoxicity could not be defined based on the present experiments. [ABSTRACT FROM AUTHOR]

Abstract: The role of the tobacco-alkaloid nicotine in tumour biology is widely discussed in the literature. Due to a strong capacity to induce angiogenesis, a pro-mutagenic potential in non-tumour and cancer cells, and a pro- and anti-apoptotic influence, nicotine seems to promote the growth of established tumours. However, results indicating DNA damage and genetic instability associated with nicotine have been contradictory thus far. A variety of markers and endpoints of genotoxicity are required to characterize the genotoxic potential of nicotine. Induction of DNA single- and double-strand breaks, the formation of micronuclei, and the induction of sister chromatid exchange and chromosome aberrations represent possible genotoxicological endpoints at different cellular levels. Human lymphocytes were exposed to nicotine concentrations between 1μM and 1mM for 24h in vitro. The comet assay, the cytokinesis-block micronucleus test, the chromosome aberration (CA) test, and the sister chromatid exchange (SCE) test were then applied. Viability and apoptosis were measured by flow cytometry in combination with the annexin V-propidium iodide staining test. In this test setting, no enhanced DNA migration was measured by the comet assay. An increase in the micronucleus frequency was detected at a concentration of 100μM nicotine without affecting the frequency of apoptotic cells. A distinct genotoxic effect was determined by the CA test and the SCE test, with a significant increase in CA and SCE at a concentration of 1μM. In the annexin V test, nicotine did not influence the proportion of apoptotic or necrotic cells. The current data indicating the induction of CA by nicotine underscore the necessity of ongoing investigations on the potential of nicotine to initiate mutagenesis and tumour promotion. Taking into account the physiological nicotine plasma levels in smokers or in nicotine-replacement therapy, particularly the long-term use of nicotine should be critically discussed. [Copyright &y& Elsevier]

Abstract: The tobacco alkaloid nicotine is responsible for addiction to tobacco and supposed to contribute to tobacco carcinogensis, too. Recently, genotoxic effects of nicotine have been reported in human cells from blood and upper aerodigestive tract. Because of nicotine accumulation in saliva, the study of possible in vitro genotoxic effects of nicotine have been extended to human salivary gland cells. Specimens of parotid glands of 10 tumor patients were obtained from tumor-free tissue. Single cells were prepared by enzymatic digestion immediately after surgery and exposed for 1h to 0.125–4.0mM of nicotine. Possible genotoxic effects were determined by the Comet assay using the % DNA in tail (DT) as a reliable indicator of DNA damage. Nicotine induced a significant dose-dependent increase of DNA migration in parotid gland single-cells. The mean DT was 1.12-fold (0.125mM) to 2.24-fold (4.0mM) higher compared to control. The lowest concentration eliciting significant DNA damage within 1h, 0.25mM nicotine, is only 10-fold higher than maximal concentrations of nicotine reported in saliva after unrestricted smoking. Although conclusive evidence for a carcinogenic potential of nicotine is still lacking, the safety of long-term nicotine replacement therapy should be carefully monitored. [Copyright &y& Elsevier]

Abstract: Background: According to different algorithms of airway management, emergency cricothyrotomy is the final step in managing the otherwise inaccessible airway. As an alternative to an open surgical procedure, minimally invasive approaches exist. Various sets for different methods are commercially available. QuickTrach™ (VBM Medizintechnik GmbH, Sulz am Neckar, Germany) contains a plastic cannula over a metal needle for direct placement in the trachea, whereas a guide-wire is used for the actual placement of the cannula in the Melker Set™ (Cook Group Incorporated, Bloomington, IN). Objective: We hypothesize that the direct puncture involving less discrete steps is faster to perform. However, it will lead to more complications due to the higher force needed to place the relatively thick needle. Method: After approval of the local ethics committee, the study was performed on cadavers of 16 adult sheep. A wire-guided cricothyrotomy was compared with a catheter-over-needle technique. Successful placement and performance time were compared. Complication rate and maximal achieved airway pressure were evaluated. Data is given as mean and interquartile range, and Mann-Whitney U-test (p < 0.05) for significant differences. Results: With the wire-guided technique, successful placement was possible in all attempts. The catheter-over-needle method was successful in 63% and had a higher complication rate (75% vs. 13%). The cannula-over-needle method allowed a faster cricothyrotomy (32 [2–34] vs. 53 [52–56] s). Both methods allowed the delivery of similar maximal airway pressures (50 [44–51] vs. 48 [43–53] mbar). Conclusion: The wire-guided method proved to be the more reliable technique, leading to fewer complications. However, the direct puncture was faster to perform. Placed accurately, both devices allowed sufficient ventilation. [Copyright &y& Elsevier]

Titanium dioxide nanoparticles (TiO 2 -NPs) and zinc oxide nanoparticles (ZnO-NPs) are often used in sunscreens and other consumer products due to their photoprotective properties. However, concern exists regarding them possibly causing cyto- and genotoxic effects. The aim of this study was to assess cyto- and genotoxicity of these nanomaterials after single or combined exposure. For this purpose, a battery of cell culture test systems for human nasal mucosa (monolayer, air–liquid interface and mini organ culture) were exposed to 0.1–20 μg/ml of TiO 2 - and ZnO-NPs alone and in combination. Cytotoxicity was measured by the MTT assay, and DNA damage and repair capacity were investigated using the comet assay. TiO 2 -NPs did not exhibit any cyto- or genotoxic potential within the tested concentrations. However, results of the study indicated cyto- and genotoxicity resulting from ZnO-NPs. The genotoxicity could be antagonized by TiO 2 -NPs. Furthermore, the DNA repair capacity after ZnO-NP-induced DNA damage was enhanced by TiO 2 -NPs. The adsorption of dissolved zinc ions onto TiO 2 -NPs is discussed as the major antagonistic mechanism. The combination of both metal oxide nanoparticles interferes with the genotoxicity of ZnO-NPs and should be discussed as a reasonable and safe alternative to the sole use of ZnO-NPs in consumer products. [ABSTRACT FROM AUTHOR]

In patients with chronic rhinosinusitis with nasal polyps (CRSwNP), a relative accumulation of cluster of differentiation (CD)8+ T cells over CD4+ T cells occurs in nasal polyps compared with the peripheral blood. Nasal CD8+ T cells and CD4+ T cells predominantly present an effector memory phenotype. Immunological studies have reported that memory T cells recirculate from the tissues to the peripheral blood and a high percentage of these T cells persist within the tissue. The aim of the present study was to characterize CD69+ sphingosine‑1‑phosphate receptor 1 (S1PR1)‑ tissue resident memory T cells (Trm) in the polyps of patients with CRSwNP. Tissue and blood samples were collected from 10 patients undergoing nasal sinus surgery. Expression of specific extra‑ and intracellular molecules were analyzed using multicolor flow cytometry. A significantly higher level of CD8+ T cells than CD4+ T cells was present in nasal polyps, while significantly more CD4+ T cells than CD8+ T cells were detected in the peripheral blood of patients with CRSwNP. The frequency of CD69+ T cells was significantly higher in CD8+ and CD4+ T cells in nasal polyps compared with the peripheral blood. The frequency of CD69+ S1PR1‑ Trm was also significantly higher in CD4+ and CD8+ T cells from nasal polyps compared with the peripheral blood. Within polyps, the frequency of CD69+ S1PR1‑ Trm was again significantly higher in CD8+ compared with CD4+ T cells. In summary, a significantly higher frequency of CD69+ S1PR1‑ T cells was observed in the nasal polyps compared with the peripheral blood in patients with CRSwNP. The results of the present study suggest that local regulation of the immune response occurs within nasal polyps. As such, Trm should be considered a potential stimulus in the pathogenesis of nasal polyps. However, the role of Trm in nasal polyps as a pathogenic trigger of the local inflammatory reaction requires further investigation.

Objectives: The pathophysiological mechanisms of chronic rhinosinusitis with nasal polyposis (CRSwNP) still are discussed controversially. Regulatory B cells (B reg ) are responsible for the suppression of T cell activity: deficiencies for B reg have been demonstrated to contribute to autoimmune disorders, e.g., systemic lupus erythematosus. In order to evaluate the influence of B cell subpopulations, especially B reg , on the etiology of this disease, the aim of this study was to characterize subpopulations of peripheral and edaphic B cells in CRSwNP., Methods: Polypoid tissue and blood samples were collected from 10 patients undergoing paranasal sinus surgery and lymphocytes were analyzed by multicolor flow cytometry., Results: There was a significantly lower frequency of B cells in nasal polyps compared to peripheral blood mononuclear cells (PBMC) in patients with CRSwNP. Mature resting B cells were the main population within B cells in PBMC, and memory B cells in nasal polyps. Remarkably, B reg and mature B cells significantly decreased in nasal polyps compared to PBMC. Memory B cells significantly increased and represented the main subpopulation in nasal polyps in patients with CRSwNP., Conclusion: In this study a detailed contemporary characterization of B cell subpopulations in patients with CRSwNP is presented. The influence of edaphic B cells could play a key role in the maintenance of this chronic infectious disease.

Background: There is an ongoing discussion concerning the potential origins of chronic rhinosinusitis with nasal polyposis (CRSwNP)., Objective: The aim of this study was to quantify subpopulations of T cells in peripheral blood and nasal polyps in CRSwNP to examine their influence on the etiology of this disease., Methods: Tissue and blood samples were collected from 11 patients who underwent nasal sinus surgery, and these samples were analyzed by multicolor flow cytometry., Results: There was a significantly lower frequency of CD4+ T-helper (Th) cells and a significantly higher frequency of CD8+ T cells among lymphocytes isolated from nasal polyps compared with peripheral blood mononuclear cells (PBMC). In both T-cell subpopulations, a shift mainly from naive T cells among peripheral blood lymphocytes toward an effector memory and terminally differentiated subtype predominance in nasal polyps was observed. Among CD4+ T cells, the frequencies of cluster of differentiation (CD) 45RA- Forkhead-Box-Protein P3high (FoxP3high) cytotoxic T-lymphocyte-associated Protein 4high (CTLA-4high) activated regulatory T (Treg) cells, and CD45RA- Forkhead-Box-Protein P3low (FoxP3low) memory T cells were significantly increased in nasal polyps compared with PBMC., Conclusion: In this study, we presented a detailed characterization of CD4+ and CD8+ T-cell subpopulations in patients with CRSwNP. CD8+ T cells were more prominent in nasal polyps than in CD4+ T cells. Both nasal CD8+ T cells and CD4+ T cells predominantly had an effector memory phenotype. Among CD4+ T cells, activated Treg cells were increased in nasal polyps compared with PBMC. The data point toward a local regulation of T-cell composition within the microenvironment of nasal polyps, which might be further exploited in the future to develop novel immunotherapeutic strategies.

Sebaceous lymphadenoma is a rare benign neoplasm presenting predominantly in the parotid gland or in periparotid lymph nodes. It rarely transforms into a malignant tumor. We present a sebaceous lymphadenoma with an unusual clinical presentation with a malignant component, infiltration of lymph nodes, and lymphangiosis carcinomatosa. Sebaceous lymphadenoma usually presents as a well-circumscribed, painless, infraauricular mass. In our 87-years-old male patient, the clinical presentation was confluent reddish livid plaques at the left cheek and the left neck. In addition, cervical lymph node metastases were suspected. After skin biopsy, the tumor was excised by parotidectomy, skin excision, and neck dissection followed by a postoperative radiotherapy. To our knowledge, this is the sixth reported case of sebaceous lymphadenocarcinoma and the first case presenting with cervical lymph node metastases and dermatological symptoms revealing lymphangiosis carcinomatosa.

The aim of this study was to determine the photocatalytic effects of zinc oxide (ZnO) NPs in combination with UVA-1 in human head and neck squamous cell carcinoma (HNSCC) cell lines in vitro. NP characteristics and intracellular distribution were described by transmission electron microscopy (TEM). After pre-incubation with ZnO NPs in concentrations of 0.002-20 µg/ml, the HNSCC cell lines HLaC 78 and UD-SCC 7A as well as primary oral mucosa cells (pOMCs) were treated with UVA-1. Cell survival and vitality was observed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide-(MTT)-assay and fluorescein diacetate test. Apoptosis was assessed by annexin-V propidium iodide flow cytometry. Intranuclear distribution of the rod-shaped particles was observed in 3.5% of HNSCC and in 0.5% of pOMCs. UVA-1 irradiation of 15 min in combination with 0.2 and 2 µg/ml of ZnO NP dispersion was shown to reduce the vitality of cancer cell lines significantly in comparison to cells without NP exposure or UVA-1 treatment only. For HLaC 78, a significant reduction in viable cells was already seen at 10 min of UVA-1 treatment and a ZnO NP concentration of 2 µg/ml. Flow cytometry indicated that cell death occurred primarily through necrosis. In pOMCs, vitality was not influenced either by UVA-1 treatment or ZnO NP exposure up to 2 µg/ml or a combination of both. ZnO NPs showed cytotoxicity at 20 µg/ml without UVA-1. Due to their photocatalytic properties, ZnO NPs may induce cell death in human HNSCC cell lines in vitro. Further studies will evaluate a possible benefit in adjuvant cancer therapy.