Relocation of an infected tracheostoma: anterior mediastinal tracheostomy as Mission:Impossible.

Infected tracheostomas are frequently associated with high morbidity and mortality rates-especially in patients after neck-oncological surgery with subsequent radiochemotherapy. A 59-year-old male patient with a history of hypopharynx carcinoma, successive laryngectomy and adjuvant radiochemotherapy developed an oesophagotracheal fistula with massive inflammation and periodical bleedings, uncontrollable by regular stent alternations. In a multidisciplinary setting, the decision was made to treat the patient with an anterior mediastinal tracheostomy. Extending usual anterior mediastinal tracheostomy indications, we present an ultimate treatment option for infected tracheostomas and highly advocate this interdisciplinary venture, as it significantly improves quality of life.

Multikinase inhibitors sorafenib and sunitinib as radiosensitizers in head and neck cancer cell lines.

BACKGROUND: Radioresistance is a common feature of head and neck squamous cell carcinoma (HNSCC). We previously showed that the irradiation- activated vascular endothelial growth factor (VEGF)-extracellular signal-regulated kinase (ERK)-axis is fundamental for the survival of resistant tumors. In this study, we examined if treatment with potent multikinase (MK) inhibitors, sorafenib and sunitinib, could radiosensitize tumor cells. METHODS: Cultured HNSCC cell lines were treated with inhibitors and subsequently irradiated. Radiosensitizing effects were functionally assessed by annexin-V apoptosis and clonogenic assays and confirmed by Western blot. Additionally, we surveyed human HNSCC tissue microarrays (TMAs) for activated ERK expression. RESULTS: Based on combination indexes, we found that combining irradiation with both inhibitors exerted strong and supra-additive antitumor effects on clonogenic survival. Kinase inhibition enhanced irradiation-induced apoptotic rates and inhibited postradiogenic phospho-ERK-expression. Patients with recurrent HNSCC displayed significantly lower extracellular signal-regulated kinase phosphorylation (pERK) levels than relapse-free patients. CONCLUSION: We propose further evaluation of sorafenib and sunitinib as potential radiosensitizing agents in HNSCC treatment. © 2017 Wiley Periodicals, Inc. Head Neck 39: 623-632, 2017.

International Consensus Statement on Allergy and Rhinology: Rhinosinusitis.

BACKGROUND: The body of knowledge regarding rhinosinusitis(RS) continues to expand, with rapid growth in number of publications, yet substantial variability in the quality of those presentations. In an effort to both consolidate and critically appraise this information, rhinologic experts from around the world have produced the International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR:RS). METHODS: Evidence-based reviews with recommendations(EBRRs) were developed for scores of topics, using previously reported methodology. Where existing evidence was insufficient for an EBRR, an evidence-based review (EBR)was produced. The sections were then synthesized and the entire manuscript was then reviewed by all authors for consensus. RESULTS: The resulting ICAR:RS document addresses multiple topics in RS, including acute RS (ARS), chronic RS (CRS)with and without nasal polyps (CRSwNP and CRSsNP), recurrent acute RS (RARS), acute exacerbation of CRS (AECRS), and pediatric RS. CONCLUSION: As a critical review of the RS literature, ICAR:RS provides a thorough review of pathophysiology and evidence-based recommendations for medical and surgical treatment. It also demonstrates the significant gaps in our understanding of the pathophysiology and optimal management of RS. Too often the foundation upon which these recommendations are based is comprised of lower level evidence. It is our hope that this summary of the evidence in RS will point out where additional research efforts may be directed.

Olfaction in chemotherapy for head and neck malignancies.

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 next cycle. For evaluation of sense of smell, the established Sniffin' Sticks test with a determination of threshold, discrimination and identification (TDI) was used. Thirty-three patients (44-85 years old, 25 men and 8 women) were included in the study. Most malignancies were located in the oropharynx. RESULTS: Among the 28 patients who scored normosmic or hyposmic at the beginning of the study, the mean decrease in TDI-score was 0.72 points (24.0-23.2) in the first cycle, 2.1 points (24.5-22.4) in the second cycle and 0.77 points (24.2-23.4) in the third cycle. The decrease during the second cycle was significant. Age (>55 years) had a significant (negative) influence in the first and the second cycles. Smoking only showed a tendency to decreased TDI-scores in chemotherapy. In-between consecutive cycles an increase in TDI-score was obvious (+1.0 points after the first and +1.5 points after the second cycle). CONCLUSION: Chemotherapy with cisplatin, 5-fluorouracil and docetaxel significantly affected sense of smell to a small extent. This effect was more pronounced in elderly patients and smokers. This fact must be taken into account as a possible additional negative effect in usually prevailing malnutrition in these patients. Furthermore, no cumulative effect of the administered therapeutic agents on olfaction could be proven during this study and recovery occurred within a 3-week period.

Controlled trial for long-term low-dose erythromycin after sinus surgery for chronic rhinosinusitis.

OBJECTIVES/HYPOTHESIS: The efficacy of macrolides in chronic rhinosinusitis (CRS) is still under controversy. To date, only two double-blind, placebo-controlled studies have been published with differing results. None of these studies investigated the possible benefit of macrolides in the postoperative period. We conducted an investigator-initiated clinical trial using 250-mg erythromycin once a day over a period of 3 months, beginning the administration of either erythromycin or placebo 2 weeks after a surgical intervention for CRS. STUDY DESIGN: Randomized double-blind, placebo-controlled trial. METHODS: The concentrations of eosinophilic cationic protein (ECP) and myeloperoxidase in nasal secretion were chosen as primary outcome measures. Additionally, as a secondary outcome measure, changes in the Sino-Nasal Outcome Test-20 score, olfaction, saccharin transit time, nasal endoscopy score, and self-rating of nasal health using a visual analogue scale were evaluated. RESULTS: Sixty-seven patients after surgery for CRS with or without nasal polyps were screened, and 58 patients were randomized to the study groups. For the primary outcomes, the concentrations of ECP changed from 176.4 µl/l ± 79.0 to 226.1 µl/l ± 200.6 in the erythromycin group and from 186.9 µl/l ± 36.0 to 192.9 µl/l ± 189.2 in the placebo group; no statistical differences were found. Of the secondary outcomes, only the nasal endoscopy score showed a statistically significant improvement in the erythromycin group (from 2.6 ± 1.4 to 1.9 ± 1.5 points) compared to the placebo group (from 2.5 ± 1.3 to 2.6 ± 1.5 points). The subgroup of patients without nasal polyps in the erythromycin group showed a tendency to improvement in some secondary outcome criteria. CONCLUSIONS: A general recommendation for long-term, low-dose erythromycin treatment after surgery for CRS cannot be given. In patients with CRS without nasal polyps, a tendency to improved parameters was detected. LEVEL OF EVIDENCE: Ib.

Adenoids of patients with mucopolysaccharidoses demonstrate typical alterations.

OBJECTIVE: Tonsillar hypertrophy caused by the progressive accumulation of partially degraded glycosaminoglycans (GAGs) within the cells is a typical symptom in patients with mucopolysaccharidoses (MPS). We studied the tissue of adenoids and tonsils of patients suffering from MPS with special regard to characteristic morphological features serving as possible markers for diagnosis. METHODS: Adenoids of 87 patients and tonsils of 4 patients with MPS (2 patients with MPS I, 7 MPS II, 5 MPS IV and 10 MPS VI and 63 controls) and controls were examined. Examinations were repeated in a blinded manner by two pathologists. RESULTS: The key feature observed was a subepithelial "clearing" on scanning magnification, induced by perivascular accumulation of histiocytoid cell forms. Similar agglomerates could sometimes be found at the base of lymphoid follicles. In the blinded assessment a specificity of 92% (100% for adenoids) and a sensitivity of 100% were achieved. The inter-observer-consistency was 92% (100% for adenoids). In tonsillectomy specimens marked subepithelilal fibrosis can lead to a false-negative evaluation. CONCLUSIONS: Qualified histological examination could be an option for early diagnosis of MPS.

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. All of the investigators were blinded to the origin of the specimens. The expression levels of fascin were significantly increased in the tumor tissues (P=0.03) and lymph node metastases (P=0.03) compared with that of the normal tissues. The high expression level of fascin in the tumor tissues was correlated with the N-status, however, not with overall survival. Therefore, fascin may be a suitable marker for the prediction of regional lymphatic metastasis in HNSCC.

Phenotypic variability and risk of malignancy in SDHC-linked paragangliomas: lessons from three unrelated cases with an identical germline mutation (p.Arg133*).

CONTEXT: Mutations in the four subunits of succinate dehydrogenase (SDH) are the cause for the hereditary paraganglioma (PGL) syndrome types 1-4 and are associated with multiple and recurrent pheochromocytomas and PGLs. SDHC mutations most frequently result in benign, nonfunctional head-and neck PGLs (HNPGLs). The malignant potential of SDHC mutations remains unclear to date. OBJECTIVES: We report a patient with malignant PGL carrying a SDHC mutation and compare her case with two others of the same genotype but presenting with classic benign HNPGLs. Loss of heterozygosity (LOH) was demonstrated in the malignant PGL tissue. DESIGN: In three unrelated patients referred for routine genetic testing, SDHB, SDHC, and SDHD genes were sequenced, and gross deletions were excluded by multiplex ligation-dependent probe amplification (MLPA). LOH was determined by pyrosequencing-based allele quantification and SDHB immunohistochemistry. RESULTS: In a patient with a nonfunctioning thoracic PGL metastatic to the bone, the lungs, and mediastinal lymph nodes, we detected the SDHC mutation c.397C>T predicting a truncated protein due to a premature stop codon (p.Arg133*). We demonstrated LOH and loss of SDHB protein expression in the malignant tumor tissue. The two other patients also carried c.397C>T, p.Arg133*; they differed from each other with respect to their tumor characteristics, but both showed benign HNPGLs. CONCLUSIONS: We describe the first case of a malignant PGL with distant metastases caused by a SDHC germline mutation. The present case shows that SDHC germline mutations can have highly variable phenotypes and may cause malignant PGL, although malignancy is probably rare.

Non-pheochromocytoma (PCC)/paraganglioma (PGL) tumors in patients with succinate dehydrogenase-related PCC-PGL syndromes: a clinicopathological and molecular analysis.

OBJECTIVE: Although the succinate dehydrogenase (SDH)-related tumor spectrum has been recently expanded, there are only rare reports of non-pheochromocytoma/paraganglioma tumors in SDHx-mutated patients. Therefore, questions still remain unresolved concerning the aforementioned tumors with regard to their pathogenesis, clinicopathological phenotype, and even causal relatedness to SDHx mutations. Absence of SDHB expression in tumors derived from tissues susceptible to SDH deficiency is not fully elucidated. DESIGN AND METHODS: Three unrelated SDHD patients, two with pituitary adenoma (PA) and one with papillary thyroid carcinoma (PTC), and three SDHB patients affected by renal cell carcinomas (RCCs) were identified from four European centers. SDHA/SDHB immunohistochemistry (IHC), SDHx mutation analysis, and loss of heterozygosity analysis of the involved SDHx gene were performed on all tumors. A cohort of 348 tumors of unknown SDHx mutational status, including renal tumors, PTCs, PAs, neuroblastic tumors, seminomas, and adenomatoid tumors, was investigated by SDHB IHC. RESULTS: Of the six index patients, all RCCs and one PA displayed SDHB immunonegativity in contrast to the other PA and PTC. All immunonegative tumors demonstrated loss of the WT allele, indicating bi-allelic inactivation of the germline mutated gene. Of 348 tumors, one clear cell RCC exhibited partial loss of SDHB expression. CONCLUSIONS: These findings strengthen the etiological association of SDHx genes with pituitary neoplasia and provide evidence against a link between PTC and SDHx mutations. Somatic deletions seem to constitute the second hit in SDHB-related renal neoplasia, while SDHx alterations do not appear to be primary drivers in sporadic tumorigenesis from tissues affected by SDH deficiency.

Cholesteatoma of the hypotympanum in a patient with Treacher Collins syndrome.

In the present article we report a cholesteatoma of the hypotympanum extending to the jugular foramen in a 16-year-old male with Treacher Collins syndrome. Preoperative imaging excluded jugular paraganglioma and set the diagnosis of cholesteatoma. We discuss the operative treatment via a large hypotympanotomy and creation of an open hypotympanic cavity. To the authors' knowledge this is the first description of hypotympanal cholesteatoma with such an extension, being treated through this approach.

Patterns of anomalies of structures of the middle ear and the facial nerve as revealed in newborn temporal bones.

HYPOTHESIS: The purpose of this study is to offer new data about facial nerve malformations in the tympanic cavity. BACKGROUND: Prospective anatomic study of newborns to demonstrate the submacroscopic anatomy of the intratympanic facial nerve and its surrounding structures by malformations. METHODS: Step-by-step microdissection of 12 newborn temporal bones and histologic evaluation of 4 middle ears showing multiple malformations. RESULTS: Four of 12 temporal bones presented malformation in the middle ear. All 4 temporal bones showed developmental failures of the stapes, and 3 of them had malposition of the tympanic portion of the facial nerve. In 3 cases, there was an oval window atresia, and in 1 case, the rim of the oval window was not ossified and was positioned medial to the stapes. CONCLUSION: Malformation or displacement of the stapes can be an indirect sign for facial nerve malformation. The most common site for facial nerve malformation is the tympanic portion. The tympanic segment of the nerve is devoid of bony covering in association with these anomalies of the stapes.

Reactive oxygen species activation of MAPK pathway results in VEGF upregulation as an undesired irradiation response.

BACKGROUND: Radioresistance limits the effectiveness of radiotherapy in head and neck squamous cell carcinoma. We previously demonstrated post-radiogenic mitogen-activated protein kinase (MAPK) pathway activation and vascular endothelial growth factor (VEGF) release resulting in reduced tumor cell response. Here, we examined the association of this mechanism with the induction of reactive oxygen species (ROS) under irradiation (IR). METHODS: Intracellular ROS after IR were measured. We modeled radiation-induced ROS by exposure of two SCC lines to H2 O2 and evaluated the impact of irradiation and ROS on ERK phosphorylation by Western blot, immunohistochemistry, and ELISA. RESULTS: We found elevated pERK levels after treatment with IR and H2 O2 , which could be distinctly suppressed by U0126. Immunohistochemistry and ELISA revealed increased intracellular VEGF levels after H2 O2 application. CONCLUSIONS: Our data show that irradiation-induced ROS activate the MAPK pathway and release of VEGF. As VEGF is known to be released after cellular distress resulting in cytoprotection, the described mechanism is potentially of importance for therapy success.

Malignant and benign sinonasal paragangliomas.

OBJECTIVES/HYPOTHESIS: To report on the clinical course and management of sinonasal paragangliomas (PGLs). STUDY DESIGN AND METHODS: Retrospective chart review of six patients with PGLs of the nasal cavity and paranasal sinuses. RESULTS: Three patients had tumors with malignant clinical behavior with cerebral metastases or infiltration of brain and local recurrence, despite surgery and/or radiotherapy, while three patients demonstrated a benign course. CONCLUSION: Sinonasal paragangliomas are frequently malignant. If malignant, they are very aggressive, with rapid local spread as well as high metastatic potential despite surgical resection; and they have a poor prognosis. Malignancy cannot be diagnosed on histology, but only on the basis of clinical behavior. Intracranial metastasis is commonly expected. Long-term follow-up, with particular emphasis put on the intracranial structures, is mandatory as recurrences or metastasis may occur even after a long time interval.

High incidence of extraadrenal paraganglioma in families with SDHx syndromes detected by functional imaging with [18F]fluorodihydroxyphenylalanine PET.

PURPOSE: Knowledge of the genetic backgrounds of hereditary syndromes, which are increasingly being characterized, enables genetic screening of family members of affected patients. Upon detection of a mutation, genetic counselling and clinical screening including imaging modalities and biochemical analyses are commonly performed. METHODS: Unaffected, mutation-positive relatives of index patients with hereditary paraganglioma syndromes were offered PET imaging with [(18)F]fluorodihydroxyphenylalanine and the incidence of pathological findings was retrospectively analysed in relation to mutations of the succinate dehydrogenase enzyme complex. PET only or PET/CT was performed in 21 individuals from eight families with SDHD, one family with SDHC and two families with SDHB mutations. Screening was offered every 2 to 5 years. RESULTS: Of the 21 individuals, 14 showed paraganglioma during screening. In particular, in only 2 of 15 patients with a SDHD mutation were the findings completely unremarkable on PET screening. However, false-negative lesions for abdominal manifestations in two SDHD-positive patients were detected. CONCLUSION: FDOPA PET is a sensitive imaging modality which should be offered to patients with a detected SDHx (SDHD) mutation, preferably using a hybrid technique.

Treatment for adult idiopathic and Wegener-associated subglottic stenosis.

The aim of the study is to present the results of combination treatment for adult non-traumatic subglottic stenosis (SGS). This is a retrospective chart review of 12 female patients (age range 32-76 years) with idiopathic SGS (eight patients) and Wegener's granulomatosis. All patients had a hard and 11 a short (less than 1 cm) stenosis. Eleven patients were treated with endoscopic CO(2) laser, one with Nd-YAG laser. Topical triamcinolone was applied to all. In 10 patients, topical mitomycin C (MMC) was additionally applied. Symptom severity and airway resistance (AR) were evaluated pre- and post-interventionally. Postoperatively, oral steroids (and/or methotrexate) and proton pump inhibitors (PPI) were prescribed. Follow-up period ranged between 7 and 115 months. All patients reported a significant improvement in obstructive symptoms. Average AR preoperatively was 1.004 kPa/(L/s) and postoperatively 0.526 kPa/(L/s). Three patients underwent surgery once, 2 required a second surgery, 5 were operated 3 times, one 5 times, and one 7 times. The latter two patients had not received local MMC treatment. Endoscopic laser surgery combined with local MMC and triamcinolone application and postoperative oral steroid/methotrexate and PPI therapy provides a treatment option that results in prolongation of the symptom-free time intervals and avoidance of open surgery in patients with idiopathic and Wegener-associated hard and short SGS.

Short-term hearing results after primary stapedotomy with nitinol and teflon-platinum prostheses for otosclerosis.

The aim of this study is to determine differences in postoperative air-bone gap (ABG) after placement of teflon-platinum or nitinol middle ear prostheses in primary stapedotomy patients with otosclerosis. Thirty otosclerosis patients (24 female, 6 male; age 10-61 years) with primary stapedotomy were studied prospectively. Before and after surgery, the mean and standard deviations of the ABG were measured at eight frequencies (0.25-4 kHz). Patients were randomized into one of two groups receiving either teflon-platinum or nitinol prostheses. Hearing results were assessed 1 year after surgery. To assess the joint influence of treatment and frequency on ABG reduction, a linear mixed model was used (significance level was p = 5%). The Tukey-Kramer method was used to adjust for multiple comparisons. Significant differences were found between treatment groups (p < 0.0001) and between frequencies within the same treatment group (p < 0.0001) but no interaction (p = 0.7963), i.e. the reduction of the conductive components over frequencies was nearly parallel in both groups. Overall, patients in the Teflon group had a larger reduction of conductive components, on average 8.0 dB more reduction, than patients in the nitinol group. However, after adjusting for multiple comparisons, we could not identify a single frequency with a significant difference in reduction of conductive components. Use of the teflon-platinum prosthesis results in statistically non-significant better ABG closure at 0.25-4 kHz 1 year postoperatively than the use of the nitinol prosthesis.

Cancer-associated fibroblasts do not respond to combined irradiation and kinase inhibitor treatment.

The emergence of radioresistance is a significant issue in the treatment of squamous cell carcinoma. We recently demonstrated that post-radiogenic extracellular signal-regulated kinase (ERK) signaling might decrease radiosensitivity in this cancer type. To further elucidate how tumor-organizing cell types respond to irradiation and ERK pathway inhibition, we analyzed one oral squamous cell carcinoma and one lung cancer cell line (HNSCCUM-02T, A549), fibroblasts (NIH3T3), primary normal and cancer-associated fibroblasts (CAFs) in vitro. Irradiated cells treated with mitogen-activated protein kinase (MAPK) inhibitor U0126 were screened for pERK levels. Post-radiogenic cellular responses were functionally analyzed by proliferation and colony assays. We found analogous pERK expression, proliferation and survival of tumor and normal fibroblast cells. CAFs did not show any response to treatment. We hypothesized that radiation and MAPK inhibition have no dose-limiting effect on tumor-surrounding normal tissue. As CAFs are considered to influence the radioresponse of the entire tumor, but are not affected by treatment themselves, potential CAF-mediated tumor protection should be considered in further studies.

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 analyze survival of the cell lines. RESULTS: Compared with the nonmutated cells we observed the G12S cell line showing a clearly reduced response to inhibitor treatment under irradiation. In the case of pharmacologic inhibition of 1 of the pathways a compensatory upregulation of the second cascade leading to increased clonogenic survival seems feasible. However, there was a good functional response of this cell line to double inhibition with both compounds represented by minimized colony forming ability. The activation of ERK and Akt after irradiation was confirmed in xenotransplants showing elevated postradiogenic protein levels. CONCLUSION: With our data we confirmed our hypothesis of postradiogenic constitutive activation of the 2 pathways both required for Ras-mediated radioresistance in epithelial cells. If this effect should prove itself as a general mechanism in Ras-mutated tumors, application of specific inhibitors to block both cascades in parallel could contribute to enhance radiosensitivity in these types of cancer.

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 sinus surgery and control specimens of the inferior turbinate from individuals without CRS. Cell cultures were stimulated with recombinant vascular endothelial growth factor (VEGF(165)) and the resulting survivin expression was analyzed by Western blot. RESULTS: The survivin expression of 61 specimens was analyzed by quantitative immunohistochemistry and a potential VEGF-dependant stimulation of survivin in cell cultures was investigated. The survivin expression in nasal polyps from individuals with AERD was increased compared with the controls (median, 1194 versus 927 arbitrary units [A.U.]; p = 0.054). Western blot analysis revealed in vitro a VEGF-dependant regulation of survivin in nasal polyps from individuals without AERD, but not in those with AERD (p = 0.05). CONCLUSION: Enhanced survivin expression might result in decreased apoptosis and cellular hyperplasia as a part of the largely unknown pathophysiology of nasal polyp formation. Furthermore, we hypothesize a pathological, VEGF-independent constitutive survivin expression in nasal polyps of individuals with AERD.