Petra Ambrosch

Christian-Albrechts-Universität zu Kiel, Kiel, Schleswig-Holstein, Germany

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Publications (82)215.33 Total impact

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    ABSTRACT: Recently, we demonstrated a significant inverse correlation between HPV-infection and SLPI-expression suggesting that SLPI protects against HPV-infection of HNSCC. Here we analyzed in a single lab setting 307 formalin-fixed paraffin-embedded HNSCC cases (tonsillar n=135; non-tonsillar: n=172) from eight health care centers. Samples were analyzed for SLPI gene- and protein-expression. Annexin A2, its heterotetramer A2t, putatively facilitating HPV- and SLPI-cell entry, was measured to study the correlation between SLPI and annexin A2. Data were correlated with tobacco consumption and HPV-status. Overall, HPV-DNA prevalence was 23.5% (72/307); attributed to: 43.7% (59/135) tonsillar and 7.6% (13/172) non-tonsillar cases. Smoking resulted in 6.44-fold increased and HPV-infection in 3.46-fold decreased SLPI-gene expression in all HNSCC with similar significant results obtained in tonsillar and non-tonsillar SCC separately. Correlating annexin A2- and SLPI-gene expression showed a significant surplus of annexin A2 in HPV-positive tumors (4.21x more annexin A2) and 6.72x more annexin A2 than SLPI in nonsmokers in all HNSCC and similar significant results for both two tumor entities separately. The surplus of annexin A2 in non-smokers and HPV-positive patients supports our hypothesis that decreased SLPI levels facilitate HPV-infection i.e., increased SLPI-expression may protect against HPV-infection of tonsillar and non-tonsillar SCC.
    Cancer Letters 11/2014; 357(1). DOI:10.1016/j.canlet.2014.11.043 · 5.62 Impact Factor
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    ABSTRACT: The increased knowledge regarding HPV-infections in head and neck squamous cell carcinoma (HNSCC) has unexpectedly contributed to several uncertainties related to i) prevalence diversities depending on tumour site and geographical origin of the patients, ii) proportion of HPV-driven tumours among HPV-DNA-positive cases, and iii) identification of patients with HPV-attributed survival benefit. To investigate this heterogeneity, we analysed 307 HNSCC cases (tonsillar, n=135; non-tonsillar, n=172) from eight health care centers mostly from Northern Germany and determined HPV-DNA/mRNA and p16INK4A-status and combined results with the patient outcome. Overall HPV-DNA prevalence rate was 23.5% (72/307); attributed to: 43.7% (59/135) and 7.6% (13/172) tonsillar and non-tonsillar cases, respectively. Among these, 96.6% tonsillar and 38.5% non-tonsillar SCC were HPV-mRNA-positive. Although the study cohort was composed of patients from regions of rather close proximity, prevalence rates showed diversities of up to 40% in HNSCC subsite analysis with the lowest prevalence for tonsillar SCC in metropolitan areas (22.2%) vs. 50.9% in rural areas. Survival analysis identified p16INK4A alone as strongest predictor, followed by HPV-DNA-status alone or in combination with p16INK4A. This survival benefit was shown for tonsillar and non-tonsillar cases. Smoking significantly correlated with HPV-status, however, it does not influence survival when stratified for HPV. In conclusion, the data emphasize the urge for further data on HPV-infection in HNSCC to, e.g. clarify to what extent survival benefits of p16INK4A-positive patients are truly attributed to HPV-infections.
    International Journal of Oncology 10/2014; 46(1). DOI:10.3892/ijo.2014.2697 · 3.03 Impact Factor
  • M. Laudien · H. Petersen · P. Gotz · P. Bremer · P. Ambrosch · W. Gross · F. Moosig
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    ABSTRACT: Background Nasal involvement seems to be common in Churg-Strauss Syndrome (CSS, (1,2)). Detailed investigations of nasal function are not available. Objectives To analyze nasal function in CSS regarding especially olfactory and respiratory capacities using validated modern test systems. Methods From 6/1990 until 12/2009 96 CSS-patients (297 contacts) were included following standardized examination protocols (mean age 54, 47 female, 49 male). All patients had clinical and/or histological evidence for vasculitis and fulfilled the ACR criteria for classification. They were examined using rigid endoscopes (n=96), ENT activity score (ENTAS (3), n=37), anterior rhinomanometry (n=96), sniffin’sticks and acetic acid (n=63). Results Of 48 contacts investigated using ENTAS 38 showed no and 10 mild to high endonasal activity. By endoscopy in 86 contacts polyps, 65 septal deviations and 24 hyperplasias of the turbinates were detected. In 35 contacts (30 patients, 31%) profoundly nasal obstruction was detected and showed no correlation to ENTAS (p=0.5), polyps (p=0.7), septal deviation (p=0.5) or hyperplasia of the turbinates (p=0.08). Fourteen patients (22%) showed dysosmia. CSS-patients with compared to CSS-patients without olfactory dysfunction showed significantly less polyps (p=0.027), less often hyperplasia of the turbinates (p=0.017), less often subjective obstruction of the nose (0.002), no endonasal activity (ENTAS, p=0.04) and higher frequency of sinusitis (anamnestic data, p=0.035). No significant correlation could be detected ragarding nasal obstruction or trigeminal dysfunction and olfactory function (p=0.8, p=0.48). Compared to the general german population the risk for olfactory dysfunction is significantly increased in CSS patients Odds ratio 5.4 (95% CI 1.8 to 16, p=0.0018). Conclusions Nasal function in CSS is severely disturbed. 31% of CSS-patients suffer from profoundly nasal obstruction being one of the major complaints in chronic rhinosinusitis leading to reduced quality of life and tremendous medical costs. Olfactory dysfunction in CSS-patients compared to healthy population seems to be an effect of disease rather than obstruction and no general affection of cranial nerves was detectable. Further investigation to analyze olfactory function in detecting odors, differentiating odors and threshold as well as electrophysiological studies to differentiate peripheral and central origin of olfactory dysfunction are currently undertaken. Disclosure of Interest None Declared
    Annals of the Rheumatic Diseases 01/2014; 71(Suppl 3):682-682. DOI:10.1136/annrheumdis-2012-eular.763 · 10.38 Impact Factor
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    ABSTRACT: Palytoxin (PTX), a marine toxin isolated from the Cnidaria (zooanthid) Palythoa caribaeorum is one of the most potent non-protein substances known. It is a very complex molecule that presents both lipophilic and hydrophilic areas. The effect of PTX was investigated in a series of experiments conducted in head and neck squamous cell carcinoma (HNSCC) cell lines and xenografts. Cell viability, and gene expression of the sodium/potassium-transporting ATPase subumit alpha1 (ATP1AL1) and GAPDH were analyzed in HNSCC cells and normal epithelial cells after treatment with PTX using cytotoxicity-, clonogenic-, and enzyme inhibitor assays as well as RT-PCR and Northern Blotting. For xenograft experiments severe combined immunodeficient (SCID) mice were used to analyze tumor regression. The data were statistically analyzed using One-Way Annova (SPSS vs20). Significant toxic effects were observed in tumor cells treated with PTX (LD50 of 1.5 to 3.5 ng/ml) in contrast to normal cells. In tumor cells PTX affected both the release of LDH and the expression of the sodium/potassium-transporting ATPase subunit alpha1 gene suggesting loss of cellular integrity, primarily of the plasma membrane. Furthermore, strong repression of the c-Jun N-terminal kinase 3 (JNK3) mRNA expression was found in carcinoma cells which correlated with enhanced toxicity of PTX suggesting an essential role of the mitogen activated protein kinase (MAPK)/JNK signalling cascades pathway in the mechanisms of HNSCC cell resistance to PTX. In mice inoculated with carcinoma cells, injections of PTX into the xenografted tumors resulted within 24 days in extensive tumor destruction in 75% of the treated animals (LD50 of 68 ng/kg to 83 ng/kg) while no tumor regression occurred in control animals. These results clearly provide evidence that PTX possesses preferential toxicity for head and neck carcinoma cells and therefore it is worth further studying its impact which may extend our knowledge of the biology of head and neck cancer.
    Molecular Cancer 02/2013; 12:12. DOI:10.1186/1476-4598-12-12 · 5.40 Impact Factor
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    Zeitschrift für Rheumatologie 11/2012; 71(9):775-84. DOI:10.1007/s00393-012-0988-6 · 0.46 Impact Factor
  • M. Laudien · J. Quetz · P. Ambrosch
    Zeitschrift für Rheumatologie 11/2012; 71(9):781-782. · 0.46 Impact Factor
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    ABSTRACT: Introduction In granulomatosis with polyangiitis (GPA), a complex autoimmune small-vessel vasculitis frequently associated with chronic necrotizing inflammation of the nasal mucosa, elevated nasal Staphylococcus (S.) aureus carrier rates are a risk factor for relapse. As cytokines are primarily involved in the regulation of defense against potentially pathogenic microorganisms, the aim of this study was to compare healthy individuals and GPA patients with respect to their baseline cytokine expression of nasal epithelial cells (NEC), which form the first barrier against such triggers. The ability of S. aureus to influence the nasal microenvironment's cytokine secretion was assessed by exemplary stimulation experiments. Methods Baseline expression of 19 cytokines of primary NEC of GPA patients and normal controls (NC) was quantified by a multiplex cytokine assay. Stimulation experiments were performed with supernatants of S. aureus and expression of interleukin-8 was determined by ELISA. Results In GPA, an altered pattern of baseline cytokine expression with significantly up-regulated G-CSF and reduced interleukin (IL)-8 concentrations was observed. Both NEC of GPA patients and NC responded to stimulation with S. aureus, but GPA patients displayed a significantly lower IL-8 secretion and a diminished dynamic range of response towards the stimulus. Conclusions The data presented underline the hypothesis of a disturbed epithelial nasal barrier function in GPA. The dysregulated baseline expression of G-CSF and IL-8 and the reduced response to microbial stimulation may facilitate changes in the composition of the nasal flora and favour an imbalanced inflammatory response, which might be relevant for the disease course.
    Arthritis research & therapy 10/2012; 14(5):R203. DOI:10.1186/ar4041 · 3.75 Impact Factor
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    ABSTRACT: Granulomatosis with polyangiitis (GPA) frequently starts with an affection of the nasal and paranasal mucosa. Localised GPA of the nasal mucosa or persistent disease activity ('grumbling disease') is often encountered even under immunosuppressive therapy. Necessity for reconstructive surgery is common and careful scheduling to prevent failure and minimise revision rates is crucial. Therefore, reliable estimation of GPA activity in the upper airways using a score is mandatory for diagnosis, follow-up and scheduling reconstructive surgery. Fifty endoscopic, endonasal images of 45 patients with GPA were used. Twelve (4 German, 8 Mexican) experienced (n=7) and inexperienced (n=5) physicians assessed GPA-activity at two times (T1/T2) in dichotomy and in a grading approach (none, mild, moderate and high activity) using the novel ENT Activity Score (ENTAS). All documents were written in English. Estimation of activity in dichotomy (none vs. mild/moderate/high): Cohen's Kappa (κ) for intra-rater reliability T1/T2 in inexperienced and experienced physicians was κ=0.58 (agreement 85%) and κ=0.72 (agreement 91%). The inter-rater reliability (Fleiss's κ) T1/T2 for inexperienced and experienced physicians was κ=0.62/κ=0.59 and κ=0.50/κ=0.58 respectively. Estimation of activity in grading approach (none, mild, moderate, high): for inexperienced physicians the intra-rater reliability T1/T2 was κ=0.67 (agreement 56%) and the inter-rater reliability at T1/T2 was κ=0.29 (intraclass correlation coefficient, ICC=0.69) and κ=0.27 (ICC=0.59). For experienced physicians the intra-rater reliability T1/T2 was κ=0.80 (agreement 67%) and the inter-rater reliability at T1 and T2 was κ=0.41 (ICC=0.77) and κ=0.39 (ICC=0.75) respectively. Intra-rater reliability is high in decision in dichotomy and even in grading activity. There is no difference for experienced or inexperienced physicians. Inter-rater reliability is high in dichotomy, but low for activity grading. Thus, the ENTAS provides a reliable instrument for assessing, documenting and following GPA-related disease activity in the upper respiratory tract. The relationship of activity and following damage needs to be investigated in further studies.
    Clinical and experimental rheumatology 07/2012; 30(1 Suppl 70):S22-8. · 2.97 Impact Factor
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    ABSTRACT: Cortical attention and habituation parameters are altered in patients suffering from tinnitus. The aim of the study was to quantify cortical attention and habituation parameters in tinnitus patients by recording the contingent negative variation (CNV) response and to correlate amplitudes of different CNV parameters with duration of disease. Twenty patients suffering from tinnitus (median: 44 years) and twenty age- and sex-matched healthy controls (median: 41 years) were tested by a CNV paradigm. We recorded overall CNV, initial CNV, and terminal CNV and calculated habituation slopes. All CNV parameters were Spearman-correlated with individual duration of disease. Highly significant between groups differences emerged in total (tinnitus: -8.4 uV vs. controls: -3.8 uV), initial (-11.2 vs. -6.0 uV), and terminal CNV (-11.9 vs. -6.5 uV) demonstrating higher negative amplitudes in tinnitus patients. Habituation differed in total and terminal CNV, indicating missing habituation in tinnitus patients. Overall CNV (ϱ = -.365) and initial CNV (ϱ = -.529) showed a medium Spearman correlation with duration of disease. We conclude that the correlation between duration of tinnitus and the initial CNV amplitudes indicates an altered state of cortical excitability that can also be observed in more negative CNV-amplitudes in tinnitus patients. We assume that this state indicates a chronicity process in tinnitus disease.
    Applied Psychophysiology and Biofeedback 03/2012; 37(3):187-93. DOI:10.1007/s10484-012-9193-2 · 1.13 Impact Factor
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    ABSTRACT: First, to investigate the overall efficacy and safety of rituximab (RTX) in refractory granulomatosis with polyangiitis (GPA) in a tertiary referral centre. Second, to compare the efficacy of RTX in granulomatous and vasculitic manifestations in GPA. This study comprised a retrospective, standardised data collection from all patients who received RTX for refractory Wegener's granulomatosis from 2002 to 2010. Patients were assessed by a standardised interdisciplinary diagnostic procedure (including ear, nose and throat and ophthalmology assessment, MRI, immunodiagnostics, B-cell levels and Birmingham Vasculitis Activity Score) and were treated by standardised therapeutic regimens according to available evidence. 59 patients received 75 cycles of RTX. 9.3% achieved complete remission. A response was documented in 61.3% (improvement in 52%, unchanged disease activity in 9.3%), 26.7% had refractory disease. Birmingham Vasculitis Activity Score, disease extent index, erythrocyte sedimentation rate, C-reactive protein and prednisolone demand decreased significantly. All patients achieved B-cell depletion. Granulomatous manifestations such as orbital granuloma and pachymeningitis were more frequently refractory to RTX than vasculitis or other granulomatous manifestations. Thus, for example, complete remission/improvement was found in 89.2% of patients with renal disease and in only 44.4% of those with orbital masses (p=0.003). The relapse rate was 44.4% after a median period of 13.5 months. Adverse events occurred in 29%, pneumonia in 15% and death in 3%. The overall response rate of refractory GPA to RTX was high (61.3% complete remission or improvement). Response rates of vasculitic manifestations were excellent; failure of response/progress was mostly due to granulomatous manifestations, especially orbital masses. Relapse rates were high (40%) despite maintenance treatment.
    Annals of the rheumatic diseases 03/2012; 71(3):327-33. DOI:10.1136/ard.2011.153601 · 10.38 Impact Factor
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    ABSTRACT: Nasal carriage of Staphylococcus aureus in patients with chronic rhinosinusitis with nasal polyps (NP) is hypothesized to have pathophysiological impact on the disease. Antimicrobial peptides (AMP), especially human beta-defensin-3 (hBD-3) and LL-37, are an important part of the multifactorial defence against microorganisms in barrier organs like the nasal mucosa. The interaction of S. aureus colonization and AMP in nasal secretions and mucosa of NP were investigated in this study. AMP were quantified in nasal secretions of 13 normal controls (NC) and 12 NP patients, each with and without S. aureus colonization, by ELISA. Immunohistochemistry was used to investigate the cellular sources of AMP in the nasal mucosa. To explore the AMP response of primary nasal epithelial cell cultures (NEC) towards S. aureus stimulation, a functional assay was established. AMP could be demonstrated in nasal secretions of all groups without differences in hBD-3 concentrations comparing S. aureus carriers vs. non-carriers. In NC, higher LL-37 concentrations were observed in S. aureus colonized as compared to non-colonized patients. This effect was not detectable in NP patients. Epithelial cells, submucosal glands and cells of the connective tissue could be identified as sources of AMP by immunohistochemistry. An AMP response of NEC towards S. aureus stimulation was detected in all groups. In NP patients, LL-37 response towards S. aureus colonization is disturbed while the ability of NEC to respond on S. aureus challenge is preserved. This deregulation of the nasal barrier could be involved in the multifactorial pathophysiology of NP.
    Rhinology 12/2011; 49(5):554-61. · 2.78 Impact Factor
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    ABSTRACT: Head and neck squamous cell carcinomas (HNSCC) represent the sixth largest group among all human malignancies. However, the exact molecular mechanisms inducing the genesis and the progression of metastasis in these tumors are poorly understood. The identification of molecular alterations involved in metastasis of HNSCC might influence the value of clinical diagnostics, impact therapy strategies and finally improve the prognosis of the patients. The purpose of this study was to identify clinically relevant alterations at the transcriptional and translational levels, when comparing metastatic (N+) and non-metastatic (N0) primary HNSCC. Three transcripts HERPUD1, SLPI and RAD51 were selected for further validation based on their association with carcinogenesis and metastasis. Quantitative real-time-PCR was performed to determine the mRNA expression levels. For subsequent confirmation of the results, immunohistochemistry was performed applying a monoclonal anti-SLPI antibody on 121 HNSCC tumor specimens (N0, n=40; N+, n=81). In metastatic primary cancer, SLPI mRNA showed 5.9-fold lower expression in comparison with non-metastatic primary cancer (p=0.0092). Immunohistochemical staining revealed a fold change of -1.79 between the N+ and the N0 group (p=0.0002). The results presented here clearly indicate the repression of SLPI, measurable on both, mRNA and protein levels in metastatic primary HNSCC as compared to non-metastatic HNSCC. Therefore, it can be assumed that SLPI might have a substantial protective effect on the metastasis process of HNSCC.
    International Journal of Oncology 07/2011; 39(1):185-91. DOI:10.3892/ijo.2011.1006 · 3.03 Impact Factor
  • Joachim Quetz · Petra Ambrosch
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    ABSTRACT: Several different methods can be applied for repairing total nasal defects. Most of them are based on some common principles and techniques widely accepted and adopted by experienced surgeons. We have been using most of these techniques during the past two decades, however modifying and refining them several times. Our observations and sometimes disappointing experiences led to a concept that has remained unchanged for the past 6 years. It comprises three regular operative steps and sometimes a fourth surgical intervention for repair and refinement. First stage: Reconstruction of the septum using a bipedicled composite septal pivot flap (SPF), of the intranasal lining (INL), and the cover being established by elevating a full-thickness paramedian forehead flap (PMFF). Second stage: Re-elevation of the PMFF, thinning of its layers, and reconstruction of the subsurface framework using autogenous rib cartilage. Third stage: Division of the pedicle and minor corrections. We have been using this technique presented here since 2004 in nine consecutive patients with subtotal to supratotal nasal defects. Seven cases have been repaired completely by now and can be evaluated carefully. With this technique, results have significantly improved and have been stable to date.
    Facial Plastic Surgery 06/2011; 27(3):266-75. DOI:10.1055/s-0031-1275776 · 0.99 Impact Factor
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    ABSTRACT: Wegener's granulomatosis (WG) is a complex autoimmune disease of unknown etiology, frequently involving localized inflammation of the nasal mucosa as an early manifestation. The current hypothesis suggests that the disease is triggered by a disturbed interaction between genetic and environmental effects, such as an altered microflora at mucosal layers. In this study, a systematic assessment of 49 transcripts with potential pathophysiological relevance was performed using quantitative real-time PCR in nasal mucosa samples of more than 80 individuals, including normal control (NC) individuals and disease controls. In addition, colonization with Staphylococcus aureus was quantified in the same individuals to assess its impact on transcriptomic signatures. Transcription profiles show an increased heterogeneity in diseased individuals. In all, 10 transcripts were identified to be differentially expressed (P≤0.05, false discovery rate ≤0.05) between patients with WG and NC individuals. These transcripts include antimicrobial peptides (human β-defensin (DEFB)1: fold-change WG vs. controls: +4.45, lysozyme: -3.4, DEFB4 and S100A7 (S100 calcium-binding protein A7): both "switched on" in WG), innate immune receptors (Toll-like receptor 4: -2.1, NOD-like receptor C3: -2.1, scavenger receptor CD36: +2.9), and cytokines (interferon-γ: -14, transforming growth factor-β 1: -1.4, interleukin-17D: -2.7). These transcriptional profiles are independent of S. aureus colonization. This study for the first time describes that, on the basis of data obtained from the primary nasal tissue, WG exhibits molecular features that allow its differentiation from other inflammatory disorders with involvement of the nasal mucosa. Further studies based on these findings may enable the identification of subphenotypes, which are currently discussed as an important target for a personalized medicine approach, aiming to reduce side effects and the number of therapy non-responders.
    Mucosal Immunology 03/2011; 4(5):564-73. DOI:10.1038/mi.2011.9 · 7.54 Impact Factor
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    ABSTRACT: Nasal S. aureus carrier rates are significantly higher in patients with Wegener's granulomatosis (WG) compared to healthy controls (HC), and nasal colonisation is a risk-factor for relapse. Antimicrobial peptides (AMP) are important defence molecules maintaining an intact barrier function. It is the aim of this study to see if there is a possible link between the nasal AMP pattern and S. aureus colonisation, a link which has not been investigated so far. ELISA was applied to quantify LL-37 and hBD-3 concentrations in nasal secretions (14 WG patients, 13 HC) with and without nasal S. aureus colonisation. Immunohistochemistry was used to detect the cellular sources of AMP in the nasal mucosa. Functional analyses of primary nasal epithelial cell cultures (NEC) of these groups stimulated with S. aureus were performed. LL-37 was found in significantly higher concentrations in colonised individuals (WG: p=0.001; HC: p=0.014).Using immunohistochemistry, local cellular sources for AMP could be demonstrated. After stimulation with S. aureus, significantly higher concentrations of LL-37 and hBD-3 could be detected in the supernatant of NEC of WG patients (LL-37: p=0.001; hBD-3: p=0.001) and HC (LL-37: p=0.019; hBD-3: p=0.001). HBD-3 concentrations were significantly lower in the supernatant of stimulated NEC of WG patients compared to the NEC of HC (p=0.032), and the dynamic range of the hBD-3 answer was significantly smaller in WG compared to HC (p=0.016). The dynamic response towards challenges with microbes is dysregulated in WG, and this might be one reason for higher S. aureus colonisation rates in WG.
    Clinical and experimental rheumatology 03/2011; 29(1 Suppl 64):S49-56. · 2.97 Impact Factor
  • P Ambrosch · A Fazel
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    ABSTRACT: The principles of open vs. laser microsurgical approaches for partial resections of the larynx are described, oncological as well as functional results discussed and corresponding outcomes following primary radiotherapy are opposed. Over the last decade, the endoscopic partial resection of the larynx has developed to an accepted approach in the treatment of early glottic and supraglottic carcinomas thus leading to a remarkable decline in the use of open surgery. Comparing the various surgical approaches of laryngeal partial resections, the oncological outcome of the patients, as far as survival and organ preservation are concerned, are comparable, whereas functional results of the endoscopic procedures are superior with less morbidity. The surgical procedures put together, are all superior to radiotherapy concerning organ preservation. Transoral laser microsurgery has been used successfully for vocal cord carcinomas with impaired mobility or fixation of the vocal cord, supraglottic carcinomas with infiltration of the pre- and/or paraglottic space as well as for selected hypopharyngeal carcinomas. It has been well documented that laser microsurgery achieves good oncological as well as functional results with reasonable morbidity. However, patients with those tumours have been successfully treated by open partial resections of the larynx at medical centres with appropriate expertise. The initially enthusiastic assessment of study results concerning the efficacy of various protocols of chemoradiation with the intent of organ preservation for laryngeal and hypopharyngeal carcinomas are judged more cautious, today, due to recent reports of rather high rates of late toxicity complications.
    Laryngo-Rhino-Otologie 03/2011; 90 Suppl 1:S83-109. DOI:10.1055/s-0030-1270449 · 0.99 Impact Factor
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    Petra Ambrosch · Asita Fazel
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    ABSTRACT: The principles of open versus laser microsurgical approaches for partial resections of the larynx are described, oncologic as well as functional results discussed and corresponding outcomes following primary radiotherapy are opposed. Over the last decade, the endoscopic partial resection of the larynx has developed to an accepted approach in the treatment of early glottic and supraglottic carcinomas thus leading to a remarkable decline in the use of open surgery. Comparing the various surgical approaches of laryngeal partial resections, the oncological outcome of the patients, as far as survival and organ preservation are concerned, are comparable, whereas functional results of the endoscopic procedures are superior with less morbidity. The surgical procedures put together, are all superior to radiotherapy concerning organ preservation. Transoral laser microsurgery has been used successfully for vocal cord carcinomas with impaired mobility or fixation of the vocal cord, supraglottic carcinomas with infiltration of the pre- and/or paraglottic space as well as for selected hypopharyngeal carcinomas. It has been well documented that laser microsurgery achieves good oncological as well as functional results with reasonable morbidity. However, patients with those tumours have been successfully treated by open partial resections of the larynx at medical centres with appropriate expertise. The initially enthusiastic assessment of study results concerning the efficacy of various protocols of chemoradiation with the intent of organ preservation for laryngeal and hypopharyngeal carcinomas are judged more cautious, today, due to recent reports of rather high rates of late toxicity complications.
    01/2011; 10:Doc02. DOI:10.3205/cto000075
  • C. Werner · M. Hoffmann · V. Warneke · I. Leuschner · P. Ambrosch
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    ABSTRACT: Wir berichten über einen Patienten, der sich mit einer unklaren malignen mesenchymalen Raumforderung der Anthelix in unserer Therapie befand. Das histologische Ergebnis zeigte ein myofibroblastisches Sarkom. Myofibroblastische Sarkome sind sehr seltene Tumoren, deren genaue Zuordnung im Rahmen proliferativer Erkrankungen schwierig ist. Differenzialdiagnostisch kommen sowohl benigne als auch maligne mesenchymale Veränderungen in Betracht. Therapeutisch ist eine vollständige Resektion anzustreben, gegebenenfalls eine Kombination aus Chirurgie und Strahlentherapie. We report on a patient suffering from a mesenchymal tumour located at the antihelix. Histopathology of the tissue specimens derived from this lesion reported a myofibroblastic sarcoma, a rare tumour entity with a slight predominance of occurrence in the area of the head and neck. Grading of these tumours can be challenging since benign as well as malign phenotypes have been described. Therefore, beside complete resection of the lesion additional radiotherapy should be discussed individually. SchlüsselwörterSarkom–Myofibroblastisch–Anthelix–Mesenchymale Veränderungen–SMA-Positivität KeywordsSarcoma–Myofibroblastic–Antihelix–Mesenchymal lesion–SMA positivity
    HNO 01/2011; 59(1):61-63. DOI:10.1007/s00106-010-2195-6 · 0.54 Impact Factor
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    ABSTRACT: To determine the long-term outcome in patients with Wegener's granulomatosis (WG) over 4 decades in an academic hospital unit specializing in rheumatology. We included 290 patients, divided them into 2 cohorts, and compared them with the historical cohort of 155 patients. Comparisons were retrospective regarding disease manifestations, therapy, mortality, and incidence of malignancies. The historical cohort (cohort 1) included 155 patients diagnosed between 1966 and 1993, cohort 2 included 123 patients diagnosed between 1994 and 1998, and cohort 3 included 167 patients diagnosed between 1999 and 2002. Over time, the interval between first symptoms and diagnosis was reduced by half (from 8 months to 4 months). Organ manifestations were similar in the 3 cohorts, and more than 80% of patients still required cyclophosphamide (CYC); however, the median cumulative dose was reduced significantly (from 67 gm in cohort 1 to 36 gm in cohort 2 and to 24 gm in cohort 3). The standardized mortality ratios (SMRs) declined (from 2.1 in cohort 1 to 1.41 in cohort 2 and to 1.03 in cohort 3), with fewer deaths related to WG and/or therapy (86.4% in cohort 1, 76.9% in cohort 2, 50% in cohort 3), decreasing relapse rates (63.9% in cohort 1, 51.2% in cohort 2, 35.3% in cohort 3), and no increased rate of malignancies. Compared with young females, young males had a considerably higher SMR (8.87 [95% confidence interval 4.05-16.8]) and more frequent renal manifestations (54.4% versus 33.8%). Mortality of WG patients declined over the last 4 decades, probably due to improved diagnostic and therapeutic procedures and increased awareness of WG, which led to earlier diagnosis and therapy, reduction in relapse rates, and lower cumulative CYC dose with fewer deaths related to therapy.
    Arthritis & Rheumatology 01/2011; 63(1):257-66. DOI:10.1002/art.27763 · 7.87 Impact Factor
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    ABSTRACT: To identify patients with localised Wegener's granulomatosis (locWG) to assess whether it occurs as a long-term disease stage or phenotype and to characterise its outcome. Patients in a 'localised stage' with histological criteria compatible with WG and a follow-up period of ≥1 year were included. They were prospectively followed at the Vasculitis Center Schleswig-Holstein from 1989 to 2009 and the clinical manifestations, antineutrophil cytoplasmic autoantibodies (ANCA) status and damage were evaluated. Immunosuppression was adapted to disease activity and severity in a step-up regimen. Of 1024 patients with suspected WG, 99 were clinically diagnosed with locWG and 50 fulfilled the inclusion criteria (72% women, median age 43 years, 46% ANCA-positive). The median follow-up was 48 months. All achieved a response to treatment, 34% achieved complete remission, 1-4 relapses occurred in 46%, 5 (10%) had generalised disease (median 6 years after onset). ANCA status was not associated with relapse (p=0.98), transition to generalised disease (p=0.51) or refractory manifestations (p=0.60). 47% required cyclophosphamide for localised manifestations, 36% of them for pulmonary masses and 24% for orbital masses. 66% developed organ damage, mostly due to bony destruction or space obturation (28% saddle nose, 24% septal perforation, 10% orbital wall destruction). There were two deaths that were not related to WG. There is evidence that locWG is a long-term disease stage or phenotype (5% of all patients with WG), 46% of whom are ANCA-positive. LocWG is characterised by destructive and/or space-consuming lesions associated with high relapse rates (46%) and local damage.
    Annals of the rheumatic diseases 11/2010; 69(11):1934-9. DOI:10.1136/ard.2010.130203 · 10.38 Impact Factor

Publication Stats

2k Citations
215.33 Total Impact Points

Institutions

  • 2004–2014
    • Christian-Albrechts-Universität zu Kiel
      • • Institute of Phytopathology
      • • Anatomisches Institut
      Kiel, Schleswig-Holstein, Germany
  • 2004–2013
    • University Medical Center Schleswig-Holstein
      • Department of Pediatrics
      Kiel, Schleswig-Holstein, Germany
  • 2011
    • Zhejiang Medical University
      Hang-hsien, Zhejiang Sheng, China
  • 2004–2008
    • Universitätsklinikum Schleswig - Holstein
      Kiel, Schleswig-Holstein, Germany
  • 2006
    • Deutsche Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e.V.
      Kiel, Schleswig-Holstein, Germany
  • 2000–2006
    • Universitätsmedizin Göttingen
      • Department of Otorhinolaryngology
      Göttingen, Lower Saxony, Germany
  • 1994–2006
    • Georg-August-Universität Göttingen
      • Department of Experimental Psychology
      Göttingen, Lower Saxony, Germany