Vascular endothelial growth factor expression in nasal polyps of aspirin-intolerant patients.

Objective To study differences between aspirin-tolerant patients and aspirin-intolerant patients concerning vascular endothelial growth factor (VEGF) expression. Recent publications strongly suggest the involvement of VEGF and its receptors in the pathophysiologic process of nasal polyps. Design We subjected 43 polyp specimens to semiquantitative immunohistochemical analysis. We quantified VEGF and its receptors (Flk, Flt, and neuropilin) in all samples. To gain insight into potential VEGF-mediated cellular responses, we determined proliferative (Ki67) and apoptotic (caspase 3) indices. Patients Polyp samples were obtained from 22 aspirin-intolerant patients and from 21 aspirin-tolerant pat…

Comparison of subjective olfaction ratings in patients with and without olfactory disorders

AbstractObjective:Olfactory dysfunction is common. The reliability of self-assessment tools for smell testing is still controversial. This study aimed to provide new data about the accuracy of olfactory self-assessment compared with a standardised smell test.Design:Prospective, controlled, cohort study of patients with olfactory disorders and healthy controls.Subjects:Ninety-six patients with a smell deficit and 71 controls were asked to rate their sense of smell on a visual analogue scale. Their olfactory abilities were also evaluated with the Sniffin' Sticks tests.Results:The whole cohort showed a significant correlation between visual analogue scale smell scores and Sniffin' Sticks total…

Radiofrequency tissue volume reduction for treatment of auricle keloids

Objectives/Hypothesis: Keloids are often refractive to treatment, and recurrences occur quite frequently. Radiofrequency tissue volume reduction (RFTVR) is a surgical technology that induces extensive fibrosis at the target tissues. Methods: We applied RFTVR in 14 patients (19 auricles, 5 patients treated bilaterally; 9 female, 5 male; range, 10–66 years) with keloids of the auricle. Keloids were located at the earlobe in 4 patients (5 auricles), helix in 9 patients (12 auricles), and at both earlobe and helix in 1 patient (2 auricles). In 6 patients (8 auricles) RFTVR was the sole treatment modality applied, and in 7 patients (10 auricles) intralesional steroid injection was also performed…

Olfaction in chemotherapy for head and neck malignancies

Abstract Objective Systemic chemotherapy for different malignancies occurs alongside various side effects, including reduced sensory function. To date, little is known about the effect of chemotherapeutic agents on olfaction. The aim of this study was to provide new data about changes in sense of smell during chemotherapy among patients with advanced squamous cell carcinomas of the head and neck region. Methods In a prospective, controlled cohort study of patients undergoing up to three courses of chemotherapy (cis- or carboplatin, 5-fluorouracil and docetaxel), olfaction was evaluated prior to and directly following completing a cycle, as well as 3 weeks later with the beginning of the nex…

Treg activation and their role in different subtypes of chronic rhinosinusitis

Recurrence of a laryngeal spindle cell sarcoma with a transformation into a higher grade of malignancy.

Primary malignant mesenchymal neoplasms of the larynx are rare. Sarcomas of the larynx account for <1% of all malignant laryngeal mesenchymal neoplasms. This report examines a case of a recurring laryngeal, initial benign-appearing mesenchymal tumour, which first changed its clinical phenotype without any histological signs of malignancy and later also its histological appearance with signs of malignancy. Finally, it even underwent a transformation into a higher grade of malignancy. In addition to this, the difficulties of allocating this tumour to the correct sarcoma subentity are shown.

Correlation of Skin Test Results and Specific Immunoglobulin E Blood Levels with Nasal Provocation Testing for House-Dust Mite Allergies

Background Allergen-specific immunotherapy for house-dust mite (HDM) allergies is associated with lower success rates when compared with similar treatments for other inhalant allergens, such as grass or birch. One reason might be the greater difficulty in diagnosing patients with assumed HDM allergies because symptoms occur perennially and may differ from those of a conventional allergic rhinitis. Objective The aim of the study was to compare the different methods of diagnosis in patients with assumed HDM allergy. Methods We performed a retrospective analysis of nasal provocation tests (NPT) from patients (n = 161) evaluated for Dermatophagoides pteronyssinus (n = 127) and Dermatophagoides …

No evidence for a correlation of glutathione S-tranferase polymorphisms and chronic rhinosinusitis.

OBJECTIVE: Cellular detoxification mechanisms are mandatory for cellular protection against oxidative stress and reactive oxygen species. One major group of antioxidative active enzymes involved in cellular detoxification are the Glutathione S-Transferases (GST). Multiple subtypes like GSTM1, GSTP1, and GSTT1 and variants of them are known, arising from allelic variations of the GST loci. Moreover, functional variants occur in high percentages and have been associated with diseases like bronchial asthma and bronchial hyperresponsiveness. The interplay of oxidative stress, detoxifying genes like GSTs and the genesis of respiratory tract illness is under contradictory debate. In this study, w…

Activation of mitogen-activated protein kinase extracellular signal-related kinase in head and neck squamous cell carcinomas after irradiation as part of a rescue mechanism

Background. Irradiation plays a pivotal role in head and neck squamous cell carcinoma (HNSCC) treatment. However, especially recurrent tumors frequently show increased radioresistance. We analyzed irradiation-stimulated mitogen-activated protein kinase (MAPK) signaling pathways to define cellular rescue mechanisms. Methods. Irradiated HNSCC cells were screened for MAPK activation and results were confirmed and refined by functional analyses. Extracellular signal-regulated kinase (ERK) inhibitor U0126 application enabled us to specify postradiogenic cellu- lar responses. Vascular endothelial growth factor (VEGF) levels were analyzed additionally. Results. We observed a pronounced and time-de…

Evaluation of the efficacy of the ‘nasal airflow-inducing manoeuvre’ for smell rehabilitation in laryngectomees by means of the Sniffin′ Sticks test

Clin. Otolaryngol. 2011, 36, 17–23 Objective:  To determine the efficacy of the nasal airflow-inducing manoeuvre (NAIM) as a method for olfactory rehabilitation in laryngectomees by the means of the Sniffin′ Sticks test. Study design:  Prospective open interventional trial. Setting:  Tertiary academic hospital. Participants:  Thirty-seven patients after laryngectomy have been screened and 25 patients have been included into the study. The participant’s sense of smell was tested with the Sniffin′ Sticks test before and after learning the nasal airflow inducing manoeuvre. The individual level of threshold, discrimination and identification (TDI) was determined and the individual threshold, di…

Dysregulated Survivin Expression in Nasal Polyps of Individuals with Aspirin Exacerbated Respiratory Disease

Background A derailed balance of cell proliferation and apoptosis is presumed to result in cell hyperplasia as a typical feature of nasal polyps. Survivin, a protein of the inhibitors of the apoptosis family is proposed to promote polyp formation. However, studies concerning survivin expression in chronic rhinosinusitis (CRS) with nasal polyps are rare and the specificity of the survivin expression in nasal polyps from individuals with aspirin-exacerbated respiratory disease (AERD) has not been investigated. Methods Immunohistochemical survivin expression analysis was performed. Samples were taken from the ethmoid sinus of individuals with CRS with nasal polyps with and without AERD during …

Demethylation treatment restores hic1 expression and impairs aggressiveness of head and neck squamous cell carcinoma.

Promoter hypermethylation of tumor suppressor genes is a common feature of primary cancer cells. However, at date the somatic epigenetic events that occur in head and neck squamous cell carcinoma (HNSCC) tumorigenesis are not yet been well defined. In the present study we analysed the methylation status of the gene hypermethylated in cancer-1 (hic1), a gene located on chromosome 17p13.3, a region frequently lost in HNSCC. We analysed 22 HNSCC samples and three cell lines using methylation specific PCR (MSP). We found hic1 methylated in 21 out of 22 samples and in all three cell lines. Treatment of the cell lines with the demethylating agent 5-Azacytidin (5-Aza) resulted in the demethylation…

The VEGF/VEGF-R Axis in Sporadic Vestibular Schwannomas Correlates with Irradiation and Disease Recurrence

&lt;b&gt;&lt;i&gt;Background/Aims:&lt;/i&gt;&lt;/b&gt; The molecular mechanisms downstream of mutated neurofibromatosis type 2 (NF2) gene resulting in the growth and development of vestibular schwannoma (VS) are controversial. Several lines of evidence suggest the involvement of the vascular endothelial growth factor (VEGF) pathway in VS development. Given that recent studies of VEGF blockade in patients with NF2-associated VS showed positive effects on VS growth control, we initiated this comprehensive study of the VEGF pathway in sporadic VS. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; A tissue microarray analysis of 182 sporadic VS was conducted. The expression of VEGF and its recepto…

Low-dose aspirin desensitization in individuals with aspirin-exacerbated respiratory disease

Background Nasal polyposis frequently occurs within the clinical picture of aspirin-exacerbated respiratory disease (AERD). A derailed arachidonic acid metabolism is regarded to be part of the pathophysiology of AERD, and aspirin desensitization is the only causal therapeutic option, so far. The optimal maintenance dose of aspirin desensitization to prevent nasal polyp recurrence on the one hand and to minimize aspirin-related side-effects, on the other hand, is still a matter of debate. The aim of this trial was to investigate the efficacy and safety of a low-dose aspirin desensitization protocol. Methods After sinus surgery, 70 individuals with AERD were randomly allocated to a prospectiv…

Increased radioresistance via G12S K-Ras by compensatory upregulation of MAPK and PI3K pathways in epithelial cancer

Background Irradiation-induced signaling via the 2 pathways, Raf-MEK-ERK and PI3K-Akt, is known to be closely associated with a limited response to radiotherapy. In the present study we analyzed the relevance of constitutively active K-Ras for postradiogenic pathway stimulation and the option of coordinated inhibition to overcome these rescue mechanisms. Methods We used 2 epithelial tumor cell lines as a model system, one of them harboring a G12S K-Ras mutation. Cells were irradiated and the effect of combined treatment with ionizing radiation and inhibitors on the expression of pERK and pAkt was determined by Western blotting. Additionally, clonogenic assays were performed to functionally …

Fascin upregulation in primary head and neck squamous cell carcinoma is associated with lymphatic metastasis

Fascin is an actin-bundling protein that is associated with cellular motility and cancer-cell invasion. The present study aimed to examine the expression of fascin in head and neck squamous cell carcinoma (HNSCC) and its potential use as a biomarker. In a prospective study with a median follow-up time of 48.8 months, tumor tissues, adjacent healthy tissues and cervical lymph node metastases were collected from 25 patients and analyzed by immunohistochemistry. The specimens were scored according to the intensity of fascin staining and the percentage of tumor cells stained using a semi-quantitative scoring approach; the data were analyzed and correlated with clinical follow-up observations. A…

Pharmacological genome demethylation increases radiosensitivity of head and neck squamous carcinoma cells

Aberrant inactivation of tumor suppressor genes by promoter hypermethylation has been recognized as a crucial step of tumor development and is related to aggressiveness and therapy resistance. To identify potential novel treatment strategies, we evaluated pharmacological genome demethylation for the increase of irradiation treatment effectiveness in head and neck squamous cell carcinoma (HNSCC) in this in vitro study. HNSCC cells were cultured with 2 different concentrations of 5-azacytidine (5-Aza) for 72 h, followed by a single fraction irradiation with 4 or 50 Gy, respectively. To show successful genome demethylation, the methylation status of the tumor suppressor gene hic1 (hypermethyla…

Increased basic fibroblast growth factor release and proliferation in xenotransplanted squamous cell carcinoma after combined irradiation/anti-vascular endothelial growth factor treatment.

Novel strategies of cancer therapy combine irradiation and anti-angiogenic active compounds. However, little is known concerning the undesired cellular and molecular effects caused by this novel treatment concept. We used a mouse squamous cell carcinoma (SCC) xenotransplantation model to evaluate the potential undesired effects which compromise the success of this therapeutic combination. SCCs were subcutanously implanted in nude mice. Animals were treated with a fractionated irradiation scheme (5x4 Gy) alone or in combination with daily injections of anti-vascular endothelial growth factor (VEGF) antibodies. Controls remained untreated. Before and after treatment, resonance imaging (MRI), …

Angiogenesis-related prognosis in patients with oral squamous cell carcinoma-role of the VEGF +936 C/T polymorphism.

BACKGROUND: The aim of the study was the immunohistological assessment of VEGF-single nucleotide polymorphism (SNP)-related angiogenic activity in oral squamous cell carcinoma (OSCC) in correlation with prognosis. METHODS: Fifty OSCC samples were immunostained with CD31-antibodies. Mean microvessel density (MVD) and staining intensity were determined and associated with clinicopathological/prognostic features as well as with the VEGF +936C/T SNP. RESULTS: A significant higher MVD could be seen for T3 and T4 compared with T1 and T2, N > 0 vs. N0 as well as G3–G4 vs. G1–G2 OSCCs (all: P < 0.05). A higher MVD was also associated with increased and earlier rates of local relapses, more metastas…

Low SPINK5 expression in chronic rhinosinusitis

Objectives/Hypothesis: Chronic rhinosinusitis (CRS) is a multifactorial disease that probably arises as a result of genetic diversity and environmental factors. SPINK5 is a serine protease inhibitor, which is supposed to be an important regulator of epithelial barrier maintenance. The role of SPINK5 polymorphisms and expression in CRS, especially in individuals with aspirin intolerance, is unclear. Study Design: SPINK5 single-nucleotide polymorphisms (SNPs) and SPINK5 expression levels were correlated with CRS without (CRSsNP) and with nasal polyps (CRSwNP), aspirin intolerance, asthma, and allergies. Methods: One hundred four nasal tissue samples, 15 from patients with CRSsNP, 59 from pati…

Course of olfaction after sinus surgery for chronic rhinosinusitis

Background The influence of surgery on olfaction in patients who suffer from chronic rhinosinusitis (CRS) is still not fully understood. Most particularly, the time course of the recovery is poorly studied. Methods The prospective study describes the results of the Sniffin' Sticks identification test in 41 subjects before (V1), 2 weeks after (V2), and 6 months after (V3) endonasal sinus surgery (ESS). Influencing factors (gender, revision surgery, nasal polyposis, and initial olfactory score) on the changes of the smell testing were evaluated. Results The whole cohort showed a significant improvement in Identification scores, from 8.63 to 10.24 after 2 weeks and to 10.68 after 6 months. Pat…