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Background: Only very limited data are available in the literature on the incidence of childhood cancer of the head and neck worldwide. Methods: Based on data obtained from the national German Childhood Cancer Registry, a total of 370 malignancies of the head and neck in children under the age of 15 (199 boys and 171 girls), which were reported to this institution between 1994 and 2003, were analysed in this study. Results: The overall incidence of malignancies of specific sites of the head and neck in Germany is 4.48 per 100000 children. The most frequently observed entities, representing primary tumours, are soft tissue sarcomas (0.39/100000), lymphomas (0.09/100000) and thyroid carcinoma (0.07/100000). The most commonly affected organs are the thyroid (1.21/100000), orbita (0.91/100000), nasopharynx (0.66/100000), tonsils (0.43/100000) and paranasal sinuses (0.14/100000). Overall, boys are more frequently affected than girls; however, incidence increases in girls with age and exceeds that of boys in the age group between 10 and 14 years. Conclusions: This is a first statistical evaluation detailing cumulative incidences of various histologic types of malignancies of the head and neck including age and gender distribution as well as organ-specific localization in children below the age of 15 in Germany. [ABSTRACT FROM AUTHOR]

Background/Objectives : Sinonasal malignancies are rare and highly diverse cancers that pose significant diagnostic challenges due to their variable histological features and complex anatomical locations. Accurate diagnosis is critical for guiding treatment, yet conventional methods often require multiple biopsies. This study aimed to evaluate the potential of confocal laser endomicroscopy (CLE) for real-time imaging of sinonasal tumors to characterize specific features of different entities and improve diagnostic precision. Methods : Ten patients with various sinonasal malignancies, including squamous cell carcinoma, adenocarcinoma, sinonasal undifferentiated carcinoma, olfactory neuroblastoma, sinonasal mucosal melanoma, and endonasal lymphoma, were examined using CLE during diagnostic endoscopy. CLE images were compared descriptively with histopathological cross-sections to identify unique imaging patterns for each tumor type. Results : CLE was feasible across all cases, with high-quality images obtained despite anatomical challenges in some cases. Characteristic features, such as vascular clusters in undifferentiated carcinoma, mucin-filled bubbles in adenocarcinoma, and small round cells in neuroblastoma, were identified and corresponded well with histopathological findings. CLE also helped guide biopsies by revealing areas with diagnostic relevance. Conclusions : CLE demonstrates promise as an adjunct diagnostic tool in sinonasal malignancies, offering real-time imaging that correlates with histopathological findings and aids in targeted biopsies. While this study provides preliminary insights into the utility of CLE, further research with larger cohorts and statistical validation is necessary to establish its diagnostic reliability and broader clinical application.

Background/Objectives: Building upon the rising value of Confocal Laser Endomicroscopy (CLE) in squamous cell carcinoma of the head and neck, we present the first application of CLE during the resection of sinonasal malignant melanomas. This study aims to evaluate the potential of CLE to assist surgeons in intraoperative decision-making, with a particular focus on resection margin assessment within the constrained nasal cavity. Methods: Two cases of sinonasal malignant melanoma were included in this study. CLE was employed to examine visible tumors and their margins, both pre- and post-endoscopic resection. The findings were compared to histopathological results as well as data on squamous cell carcinoma, for which malignancy criteria had already been established in prior projects. Results: CLE provided the real-time visualization of sinonasal malignant melanomas and their margins, successfully differentiating between healthy and neoplastic tissue compared to histopathological findings. Conclusion: CLE offers the potential for real-time assessment, aiding surgeons in more precise tumor resection and potentially improving patient outcomes. This study demonstrates the feasibility of using CLE in the resection of sinonasal malignant melanoma, highlighting its ability to differentiate between healthy and neoplastic tissue intraoperatively.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the mucous membranes of the nose and sinuses. Eosinophilic inflammation is described as a common endotype. The anti-IL-5 antibody mepolizumab was approved in November 2021 as an add-on therapy to intranasal glucocorticosteroids for the treatment of adults with severe chronic rhinosinusitis with nasal polyps when systemic glucocorticosteroids or surgery do not provide adequate disease control. While national and international recommendations exist for the use of mepolizumab in CRSwNP, it has not yet been adequately specified how this therapy should be monitored, what follow-up documentation is necessary, and when it should be discontinued if necessary., Materials and Methods: A literature search was performed to analyze previous data on the treatment of CRSwNP with mepolizumab and to determine the available evidence by searching Medline, Pubmed, the national and international trial and guideline registries, and the Cochrane Library. Human studies published in the period up to and including 10/2022 were considered., Results: Based on the international literature and previous experience by an expert panel, recommendations for follow-up, adherence to therapy intervals, and possible therapy breaks as well as discontinuation of therapy when using mepolizumab for the indication CRSwNP in the German healthcare system are given on the basis of a documentation sheet., Conclusion: Understanding the immunological basis of CRSwNP opens up new non-surgical therapeutic approaches with biologics for patients with severe, uncontrolled courses. Here, we provide recommendations for follow-up, adherence to therapy intervals, possible therapy pauses, or discontinuation of therapy when mepolizumab is used as add-on therapy with intranasal glucocorticosteroids to treat adult patients with severe CRSwNP that cannot be adequately controlled with systemic glucocorticosteroids and/or surgical intervention., Competing Interests: B. Wollenberg has received honoraria and/or research funding from MSD, Sanofi, AstraZeneca, Novartis, BMS Adboard outside the present work. J. Hagemann states that he has received payments for lectures and fees for advisory boards from the companies Sanofi Aventis, Novartis Pharma GmbH, and GlaxoSmithKline. A.M. Chaker provides consulting services (e.g., Advisory Boards, DSMBs), lectures, or other activities via the Technical University of Munich (TUM) or has conducted clinical studies or received research funding via TUM from: Allergopharma, ALK-Abello, AstraZenecaa, Bencard/Allergen Therapeutics, GSK, HAL Allergy, Immunotek, Novartis, SanofiGenzyme and Regeneron, Zeller AG, EIT Health, BMBF. AMC is also an officer of EUFOREA, EAACI, AeDA, and DGAKI. H. Olze has received honoraria and/or research funding from F. Hoffmann-La Roche Ltd., Sanofi-Aventis Deutschland GmbH, AstraZeneca GmbH, GlaxoSmithKline GmbH & Co KG, and Novartis Pharma GmbH. L. Klimek reports grants and/or honoraria from Allergopharma, MEDA/Mylan, HAL Allergie, ALK Abelló, LETI Pharma, Stallergenes, Quintiles, Sanofi, ASIT Biotech, Lofarma, Allergy Therapeut., AstraZeneca, GSK, Inmunotk, outside the submitted work; and membership in the following organizations: AeDA, DGHNO, German Academy for Allergology and Clinical Immunology, HNO-BV GPA, EAACI. U. Förster-Ruhrmann received honoraria for lectures from Novartis, AstraZeneca, Sanofi. and GSK outside the present work. S. Strieth reports grants from the German Research Foundation (DFG), Bonn, grants from the Head and Neck Tumor Research Foundation, Wiesbaden, grants and non-financial support from MED-EL AG, Innsbruck, personal fees from Auris Medical, Basel, personal fees from Merck Serono, Darmstadt, personal fees from Otonomy, Inc, San Diego (USA), personal fee Nordmark Arzneimittel, Uetersen, grant Andreas Fahl Medizintechnik-Vertrieb, Cologne, grant Atos Medical, Troisdorf, grant Tracoe Medical, Nieder-Olm, grants from Heimomed Heinze, Kerpen, grants from Bromepithetik, Heidelberg, grants from Fresenius Kabi, Bad Hersfeld, personnel fee from Sonofi Genzyme, Berlin, personal fee from ALK-Abelló Arzneimittel, Hamburg, outside the submitted work. M. Cuevas has received honoraria and/or non-financial support from Novartis, Sanovi-Aventis, Allergopharma, HAL Allergy, Leti Pharma, AstraZeneca, GlaxoSmithKline, ALK Abelló, Bencard Allergy, Stallergenes, and Roxall outside the submitted work and reports memberships with the following organizations: AeDA, DGHNO. A.G. Beule has received honoraria for lectures, consulting, or research activities from Allakos, AstraZenecaa, BMS, GSK, Medtronic, MSD, Novartis, Olympus, Pharmalog, Pohl Boskamp, and Sanofi Aventis outside the present work. O. Guntinas-Lichius has received honoraria from MED-EL, Merck, Novartis, MEDICE, and Merz outside the present work; and he is a member of the following organizations: DGHNO, BVHNO. T.K. Hoffmann participates in honorary advisory boards of the companies Merck, MSD, and BMS, but outside the scope of this work. C. Bachert received honoraria/research funding from the companies Sanofi, GSK, Novartis, Astra Zeneca, and ALK outside the present work. H. Wrede reports lecture fees from Allergopharma, MEDA/Mylan, HAL Allergie, LETI Pharma, Stallergenes, Sanofi, Lofarma, Allergy Therapeut., GSK outside the submitted work; and membership of the following organizations: AeDA, HNO-BV. T. Stöver has received research and study funding as well as fees for lectures and/or consultancy work from MED-EL Elektromedizinische Geräte Deutschland GmbH and Cochlear Deutschland GmbH & Co. KG outside the submitted work. He is a member of the DGHNO-KHC, the expert committee on medical devices and in-vitro diagnostics on behalf of the EU, the advisory board of the Hörzentrum Oldenburg GmbH, the task force ‘Living Practice Guidelines’, the advisory board of the Lower Saxony Center for Biomathematics, as chairman of the advisory board of the Friedberg Foundation for Hearing and Speech Promotion and as co-editor of the journal Laryngo-Rhino-Otology. C. Beutner on fees from GSK, Sanofi and Novartis, ALK Abello outside the present work. M. Laudien supported and received support, lecture, and consulting fees in the last 5 years from: Olympus Deutschland GmbH, Olympus Europa SE & CO. KG, Novartis Pharma GmbH, Sanofi-Aventis Deutschland GmbH, Brainlab Sales GmbH, GlaxoSmithKline GmbH & Co KG and the John Grube Foundation outside the present work. M. Gröger reports grants and lecture fees from Sanofi, Novartis, AstraZeneca, and GSK outside the submitted work. C. Bergmann reports on grants and fees from GlaxoSmithKline (GSK), Sanofi Aventis, Bencard Allergy GmbH/Allergy Therapeutics, HAL Allergie GmbH/HAL Allergy Holding BV outside the present work. O. Pfaar receives honoraria and/or study funding from ALK-Abelló, Altamira, Allergopharma, Stallergenes Greer, HAL Allergy Holding B.V./HAL Allergie, AAAAI, Bencard Allergy/Allergy Therapeutics, Lofarma, Biomay, Circassia, ASIT Biotech Tools S.A., Danish Consultation, Laboratorios LETI/LETI Pharma, MEDA Pharma/MYLAN, Anergis S.A., Mobile Chamber Experts, Indoor Biotechnologies, GlaxoSmithKline, Astellas Pharma Global, EUFOREA, ROXALL, Novartis, Sanofi-Aventis and Sanofi-Genzyme, Med Update Europe, streamedup!, Pohl-Boskamp, Inmunotek S.L., Wiley and Sons, Paul Martini Foundation, Regeneron Pharmaceuticals Inc, RG Aerztefortbildung, Firma Meinhardt, PneumoLIVE, Institut für Disease Management, Deutsche Forschungsgesellschaft, Springer, Thieme, AstraZeneca, Deutsche Allergie-Liga, AeDA, IQVIA Commercial, Ingress Health, Wort&Bild Verlag, Verlag ME, Procter&Gamble, Alfried-Krupp Krankenhaus, all outside the present work; and he is a member of the board/excom of the EAACI and a member of the extended board of the DGAKI. He is also the main author or co-author of various guidelines and position papers in allergology and rhinology. A.S. Hoffmann has received honoraria from GSK, Sanofi, and Novartis for lectures and advisory boards outside this work. T. Hildenbrand reports on lecture fees from AstraZeneca and Novartis outside the present work. R. Weber has received fees for lecturing and consulting activities from GSK, Infectopharm, KARL STORZ SE & Co KG, NMP, Sanofi, Sidroga-Pharma, and Stryker. W. Schlenter, S. Becker, F. Bärhold, T. Deitmer, H.J. Welkoborsky, S. Dazert, T. Huppertz, C.A. Hintschich, J. Zuberbier, C. Rudack, J. Gosepath, P. Werminghaus, F. Klimek and I. Casper have no conflicts of interest in connection with the present work. Figure 1Documentation form for the German healthcare system. Table 1.Objectifiable parameters for a response to mepolizumab therapy after 6 months (at least 1 parameter should be fulfilled) (modified from [6]). Nasal obstruction: improvement of the nasal congestion score (0 – 3) by > 0.5 or improvement of objective tests (e.g., increase in nasal inspiratory peak flow or nasal volume flow in active anterior rhinomanometry by > 20 L/min, reduction in resistance)Nasal polyp score (NPS): Reduction of the endoscopically determined NPS (0 – 8) by > 1 score point compared to the initial valueSNOT-22/quality of life: reduction in SNOT-22 score (0 – 110) by > 8.9 (validated minimum clinically relevant difference)Symptomatology in visual analog scale (VAS): reduction in total VAS symptoms (0 – 10 score points) by > 2Smelling ability: improvement in the 16-point Sniffin‘ Sticks identification test by > 3 points (validated minimum clinically relevant difference) Table 2.Objectifiable parameters for an evaluation of long-term mepolizumab therapy (> 12 months) (modified from [6]). All symptoms are only moderately pronounced or at least improved compared to the status before the start of therapyTotal nasal polyp score < 4 (added on both sides)Nasal congestion score < 2 (the nasal passage allows almost normal breathing at rest)Visual analog scale total symptoms < 5SNOT-22 value < 30Chronic rhinosinusitis with nasal polys (CRSwNP) should not currently require the administration of systemic glucocorticosteroids or surgery for CRSwNP (except surgery to remove mechanical obstructions such as synechiae, mucoceles, etc.)., (© Dustri-Verlag Dr. K. Feistle.)

(1) Background: Confocal laser endomicroscopy (CLE) has emerged as a transformative tool in head and neck surgery, with applications spanning oncologic insights and functional evaluations. This study delves into CLE's potential in these domains. (2) Methods: We performed CLE in head and neck oncologic surgery, focusing on tumor margin identification and precise resection. We also employed CLE for functional assessment in allergic rhinitis, observing real-time mucosal changes during nasal provocation testing. (3) Results: In oncologic surgery, CLE enabled real-time visualization of tumor margins and cellular patterns, aiding resection decisions. In allergic rhinitis assessment, CLE captured dynamic morphological alterations upon allergen exposure, enhancing understanding of mucosal reactions. (4) Conclusions: The integration of CLE with evolving technologies such as deep learning and AI holds promise for enhanced diagnostic accuracy. This study underscores CLE's expansive potential, highlighting its role in guiding surgical choices and illuminating inflammatory processes in the head and neck.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the mucous membranes of the nose and sinuses. Eosinophilic inflammation is described as a common endotype. The anti-IL5 antibody mepolizumab was approved in November 2021 as an add-on therapy to intranasal glucocorticosteroids for the treatment of adults with severe chronic rhinosinusitis with nasal polyps when systemic glucocorticosteroids or surgery do not provide adequate disease control. While national and international recommendations exist for the use of mepolizumab in CRSwNP, it has not yet been adequately specified how this therapy is to be monitored, what follow-up documentation is necessary, and when it should be terminated if necessary., Methods: A literature search was performed to analyze previous data on the treatment of CRSwNP with mepolizumab and to determine the available evidence by searching Medline, Pubmed, the national and international trial and guideline registries and the Cochrane Library. Human studies published in the period up to and including 10/2022 were considered., Results: Based on the international literature and previous experience by an expert panel, recommendations for follow-up, adherence to therapy intervals and possible therapy breaks, as well as termination of therapy when using mepolizumab for the indication CRSwNP in the German health care system are given on the basis of a documentation sheet., Conclusions: Understanding the immunological basis of CRSwNP opens up new non-surgical therapeutic approaches with biologics for patients with severe, uncontrolled courses. Here, we provide recommendations for follow-up, adherence to therapy intervals, possible therapy pauses, or discontinuation of therapy when mepolizumab is used as add-on therapy with intranasal glucocorticosteroids to treat adult patients with severe CRSwNP that cannot be adequately controlled with systemic glucocorticosteroids and/or surgical intervention., Competing Interests: B. Wollenberg hat Honorare und/oder Forschungsgelder von MSD, Sanofi, Astra Zeneca, Novartis, BMS Adboard außerhalb der vorliegenden Arbeit erhalten.J. Hagemann gibt an, Zuwendungen für Vorträge und Honorare für Advisory Boards von den Firmen Sanofi Aventis, Fa. Novartis Pharma GmbH und GlaxoSmithKline erhalten zu haben.A.M. Chaker führt über die Technische Universität München (TUM) Beratungsleistungen (z. B. Advisory Boards, DSMBs), Vorträge oder weitere Aktivitäten durch oder hat über die TUM klinische Studien durchgeführt oder Forschungsgelder erhalten von: Allergopharma, ALK-Abello, Astra Zeneca, Bencard/Allergen Therapeutics, GSK, HAL Allergy, Immunotek, Novartis, SanofiGenzyme und Regeneron, Zeller AG; EIT Health; BMBF. AMC ist ferner Funktionsträger der EUFOREA, EAACI, AeDA und DGAKI.H. Olze erhielt Honorare und/oder Forschungsgelder von F. Hoffmann- La Roche Ltd, Sanofi-Aventis Deutschland GmbH, AstraZeneca GmbH, GlaxoSmithKline GmbH & Co. KG und Novartis Pharma GmbH.L. Klimek berichtet über Zuschüsse und/oder Honorare von Allergopharma, MEDA/Mylan, HAL Allergie, ALK Abelló, LETI Pharma, Stallergenes, Quintiles, Sanofi, ASIT Biotech, Lofarma, Allergy Therapeut., AstraZeneca, GSK, Inmunotk außerhalb der eingereichten Arbeit, und Mitgliedschaft bei folgenden Organisationen: AeDA, DGHNO, Deutsche Akademie für Allergologie und klinische Immunologie, HNO-BV GPA, EAACI.U. Förster-Ruhrmann erhielt Honorare für Vorträge von Novartis, AstraZeneca, Sanofi und GSK außerhalb der vorliegenden Arbeit.S. Strieth berichtet über Stipendien der Deutschen Forschungsgemeinschaft (DFG), Bonn, Stipendien der Stiftung Tumorforschung Kopf-Hals, Wiesbaden, Stipendien und nichtfinanzielle Förderungen der MED-EL AG, Innsbruck, Personalhonorar von Auris Medical, Basel, Personalhonorar von Merck Serono, Darmstadt, Personalhonorar Otonomy, Inc., San Diego (USA), Personalhonorar Nordmark Arzneimittel, Uetersen, Zuschuss Andreas Fahl Medizintechnik-Vertrieb, Köln, Zuschuss Atos Medical, Troisdorf, Zuschuss Tracoe Medical, Nieder-Olm, Stipendien von Heimomed Heinze, Kerpen, Stipendien von Bromepithetik, Heidelberg, Stipendien von Fresenius Kabi, Bad Hersfeld, Personalhonorar von Sonofi Genzyme, Berlin, Personalhonorar von ALK-Abelló Arzneimittel, Hamburg, außerhalb der eingereichten Arbeit.M. Cuevas erhielt Honorare und/oder nichtfinanzielle Unterstützung von Novartis, Sanovi-Aventis, Allergopharma, HAL Allergie, Leti Pharma, AstraZeneca, GlaxoSmithKline, ALK Abelló, Bencard Allergie, Stallergenes und Roxall außerhalb der eingereichten Arbeit und berichtet über Mitgliedschaften bei folgenden Organisationen: AeDA, DGHNO.A. G. Beule hat Honorare für Vorträge, Berater- oder Forschungstätigkeiten von Allakos, Astra Zeneca, BMS, GSK, Medtronic, MSD, Novartis, Olympus, Pharmalog, Pohl Boskamp und Sanofi Aventis außerhalb der vorliegenden Arbeit erhalten.O. Guntinas-Lichius erhielt Honorare von MED-EL, Merck, Novartis, MEDICE und Merz außerhalb dieser Arbeit, und er ist Mitglied bei den folgenden Organisationen: DGHNO, BVHNO.T. K. Hoffmann nimmt an honorierten Advisory Boards der Firmen Merck, MSD und BMS teil, thematisch jedoch außerhalb der vorliegenden Arbeit.C. Bachert erhielt Honorare/Forschungsgelder von den Firmen Sanofi, GSK, Novartis, AstraZeneca und ALK außerhalb der vorliegenden Arbeit.H. Wrede berichtet über Vortragshonorare von Allergopharma, MEDA/Mylan, HAL Allergie, LETI Pharma, Stallergenes, Sanofi, Lofarma, Allergy Therapeut. und GSK außerhalb der eingereichten Arbeit und Mitgliedschaft bei folgenden Organisationen: AeDA, HNO-BV.T. Stöver erhielt Forschungs- und Studiengelder sowie Honorare für Vortrags- und/oder Beratertätigkeiten von MED-EL Elektromedizinische Geräte Deutschland GmbH und Cochlear Deutschland GmbH & Co. KG außerhalb der eingereichten Arbeit. Es bestehen Mitgliedschaften bei der DGHNO-KHC, im Expertengremium über Medizinprodukte und In-vitro-Diagnostika im Auftrag der EU, im Beirat des Hörzentrums Oldenburg GmbH, in der Task Force „Living Practice Guidelines“, im Beirat des Niedersächsischen Zentrums für Biomathematik, als Vorsitzender des Stiftungsbeirats der Stiftung zur Hör- und Sprachförderung Friedberg sowie als Mitherausgeber der Zeitschrift Laryngo-Rhino-Otologie.C. Beutner berichtet über Honorare von GSK, Sanofi und Novartis, ALK Abello außerhalb dieser Arbeit.M. Laudien unterstützte und erhielt in den letzten 5 Jahren Unterstützung, Vortrags- und Beraterhonorare von Olympus Deutschland GmbH, Olympus Europa SE & CO. KG, Novartis Pharma GmbH, Sanofi-Aventis Deutschland GmbH, Brainlab Sales GmbH, GlaxoSmithKline GmbH & Co. KG und der John Grube Foundation außerhalb der vorliegenden Arbeit.M. Gröger berichtet über Zuschüsse und Vortragshonorare von Sanofi, Novartis, AstraZeneca und GSK außerhalb der eingereichten Arbeit.C. Bergmann berichtet über Zuschüsse und Honorare von GlaxoSmithKline (GSK), Sanofi Aventis, Bencard Allergy GmbH/Allergy Therapeutics, HAL Allergie GmbH/HAL Allergy Holding BV außerhalb dieser Arbeit.O. Pfaar gibt Honorare und/oder Studiengelder von ALK-Abelló, Altamira, Allergopharma, Stallergenes Greer, HAL Allergy Holding B.V./HAL Allergie, AAAAI, Bencard Allergie /Allergy Therapeutics, Lofarma, Biomay, Circassia, ASIT Biotech Tools S.A., Dänisches Konsultat, Laboratorios LETI/LETI Pharma, MEDA Pharma/MYLAN, Anergis S.A., Mobile Chamber Experts, Indoor Biotechnologies, GlaxoSmithKline, Astellas Pharma Global, EUFOREA, ROXALL, Novartis, Sanofi-Aventis and Sanofi-Genzyme, Med Update Europe, streamedup!, Pohl-Boskamp, Inmunotek S.L., Wiley and Sons, Paul-Martini-Stiftung, Regeneron Pharmaceuticals Inc., RG Aerztefortbildung, Firma Meinhardt, PneumoLIVE, Institut für Disease Management, Deutsche Forschungsgesellschaft, Springer, Thieme, AstraZeneca, Deutsche Allergie-Liga, AeDA, IQVIA Commercial, Ingress Health, Wort&Bild Verlag, Verlag ME, Procter&Gamble, Alfried-Krupp Krankenhaus an, alle außerhalb des vorliegenden Positionspapiers, und er ist Mitglied des Vorstandes/Excom der EAACI und Mitglied des erweiterten Vorstandes der DGAKI. Ferner ist er Hauptautor oder Co-Autor diverser Leitlinien und Positionspapiere in der Allergologie und Rhinologie.A. S. Hoffmann erhielt Honorare von GSK, Sanofi und Novartis für Vorträge und Advisory Boards außerhalb dieser Arbeit.T. Hildenbrand berichtet über Vortragshonorare von AstraZeneca und Novartis außerhalb dieser Arbeit.R. Weber hat Honorare für Vortrags- und Beratungstätigkeit der Firmen GSK, Infectopharm, KARL STORZ SE & Co KG, NMP, Sanofi, Sidroga-Pharma und Stryker erhalten.W. Schlenter, S. Becker, F. Bärhold, T. Deitmer, H.J. Welkoborsky, S. Dazert, T. Huppertz, C.A. Hintschich, J. Zuberbier, C. Rudack, J. Gosepath, P. Werminghaus, F. Klimek und I. Casper haben keine Interessenkonflikte im Zusammenhang mit der vorliegenden Arbeit., (Thieme. All rights reserved.)

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the nasal and paranasal mucosa. A Type-2 inflammation is described as the most common endotype. Since October 2019 the anti-IL-4/-IL-13 antibody dupilumab has been approved in Germany as an add-on therapy to intranasal corticosteroids for the treatment of adults with severe chronic rhinosinusitis with nasal polyps, when systemic corticosteroids alone or surgery do not provide adequate disease control. While recommendations for the use of dupilumab in CRSwNP exist at both national and international levels, until now it has not been adequately established, how therapy should be monitored and when it should be discontinued in the German Health Care System., Methods: A literature search was performed analyzing previous data on the treatment of CRSwNP with dupilumab and to determine the available evidence by searching Medline, Pubmed, the national and international trial and guideline registries and the Cochrane Library. Human studies published in the period up to 05/2022 were included., Results: Based on international literature and previous experience, recommendations are given by an expert panel for follow-up and possible therapy breaks, therapy intervals or termination of therapy when using dupilumab for the indication CRSwNP in the German health care system based on a documentation form., Conclusions: Understanding the immunological basis of CRSwNP opens new non-surgical therapy approaches with biologics for patients with severe courses. The authors give recommendations for follow-up, possible therapy breaks, therapy intervals and a termination for dupilumab treatment as add-on therapy with intranasal corticosteroids for the treatment of adult patients with severe CRSwNP that cannot be adequately controlled with systemic corticosteroids and/or surgical intervention., Competing Interests: B. Wollenberg hat Honorare und/oder Forschungsgelder von MSD, Sanofi, Astra Zeneca, Novartis, BMS Adboard außerhalb der vorliegenden Arbeit erhalten.A. Sperl hat für Berater- und Vortragstätigkeit Honorare von Sanofi erhalten.J. Hagemann gibt an, Zuwendungen der Fa. Novartis Pharma GmbH für Vorträge und Honorare für advisory-borads von den Firmen Sanofi Aventis, Novartis und GlaxoSmithKline erhalten zu haben.A. Chaker führt über die Technische Universität München Beratungsleistungen (z. B. Advisory Boards, DSMBs), Vorträge oder weitere Aktivitäten für Allergopharma, ALK-Abello, Astra Zeneca, GSK, HAL Allergy, Mundipharma, Nexter, Immunotek, Lofarma, SanofiGenzyme und Regeneron durch; hat klinische Studien oder Forschungsgelder über die Technische Universität München erhalten von ALK, Allergopharma, Astra Zeneca, Bencard/Allergen Therapeutics, ASIT Biotech, GSK, Novartis, Roche, und Zeller AG, ferner Forschungsmittel erhalten vom Umweltbundesamt der Bundesrepublik Deutschland, EIT Health und DZL (BMBF). AMC hat ferner Honorare und Reisekostenerstattungen erhalten vom Bayerischen Ärzteblatt, der Deutschen Gesellschaft für Allergologie und klinische Immunologie (DGAKI) und der European Academy of Allergy and Clinical Immunology.H. Olze erhielt Honorare und/oder Forschungsgelder von F. Hoffmann- La Roche Ltd, Sanofi-Aventis Deutschland GmbH, AstraZeneca GmbH, GlaxoSmithKline GmbH & Co. KG und Novartis Pharma GmbH.L. Klimek berichtet über Zuschüsse und/oder Honorare von Allergopharma, MEDA/Mylan, HAL Allergie, ALK Abelló, LETI Pharma, Stallergenes, Quintiles, Sanofi, ASIT Biotech, Lofarma, Allergy Therapeut., AstraZeneca, GSK, Inmunotk, außerhalb der eingereichten Arbeit; und Mitgliedschaft bei folgenden Organisationen: AeDA, DGHNO, Deutsche Akademie für Allergologie und klinische Immunologie, HNO-BV GPA, EAACIU. Förster-Ruhrmann erhielt Honorare für Vorträge von Novartis, AstraZeneca, Sanofi und GSK außerhalb der vorliegenden Arbeit.S. Strieth berichtet über Stipendien der Deutschen Forschungsgemeinschaft (DFG), Bonn, Stipendien der Stiftung Tumorforschung Kopf-Hals, Wiesbaden, Stipendien und nichtfinanzielle Förderungen der MED-EL AG, Innsbruck, Personalhonorar von Auris Medical, Basel, Personalhonorar von Merck Serono, Darmstadt, Personalhonorar Otonomy, Inc., San Diego (USA), Personalhonorar Nordmark Arzneimittel, Uetersen, Zuschuss Andreas Fahl Medizintechnik-Vertrieb, Köln, Zuschuss Atos Medical, Troisdorf, Zuschuss Tracoe Medical, Nieder-Olm, Stipendien von Heimomed Heinze, Kerpen, Stipendien von Bromepithetik, Heidelberg, Stipendien von Fresenius Kabi, Bad Hersfeld, Personalhonorar von Sonofi Genzyme, Berlin, Personalhonorar von ALK-Abelló Arzneimittel, Hamburg, außerhalb der eingereichten Arbeit;M. Cuevas erhielt Honorare von AstraZeneca, GSK, Sanofi und Novartis, außerhalb dieser Arbeit;A. G. Beule hat Honorare für Vorträge, Berater- oder Forschungstätigkeiten von Allakos, Astra Zeneca, BMS, GSK, Medtronic, MSD, Novartis, Olympus, Pharmalog, Pohl Boskamp und Sanofi Aventis außerhalb der vorliegenden Arbeit erhalten.O. Guntinas-Lichius erhielt Honorare von MED-EL, Merck, Novartis, MEDICE und Merz, außerhalb dieser Arbeit; und er ist Mitglied bei den folgenden Organisationen: DGHNO, BVHNO.T. K. Hoffmann nimmt an honorierten Advisory-boards der Firmen Merck, MSD und BMS teil, thematisch jedoch außerhalb der vorliegenden Arbeit.C. Bachert erhielt Honorare/Forschungsgelder von den Firmen Sanofi, GSK, Novartis, Astra- Zeneca und ALK außerhalb der vorliegenden Arbeit.H. Wrede berichtet über Vortragshonorare von Allergopharma, MEDA/Mylan, HAL Allergie, LETI Pharma, Stallergenes, Sanofi, Lofarma, Allergy Therapeut., GSK, außerhalb der eingereichten Arbeit; und Mitgliedschaft bei folgenden Organisationen: AeDA, HNO-BV.T. Stöver erhielt Forschungs- und Studiengelder sowie Honorare für Vortrags- und/ oder Beratertätigkeiten von MED-EL Elektromedizinische Geräte Deutschland GmbH und Cochlear Deutschland GmbH & Co. KG, außerhalb der eingereichten Arbeit. Es bestehen Mitgliedschaften bei der DGHNO-KHC, im Expertengremium über Medizinprodukte und in-vitro-Diagnostika im Auftrag der EU, im Beirat des Hörzentrum Oldenburg GmbH, in der Task Force ‚Living Practice Guidelines‘, im Beirat des Niedersächsischen Zentrums für Biomathematik, als Vorsitzender des Stiftungsbeirats der Stiftung zur Hör- und Sprachförderung Friedberg sowie als Mit-Herausgeber der Zeitschrift Laryngo-Rhino-Otologie.C. Beutner berichtet über Honorare von GSK, Sanofi und Novartis, ALK Abello außerhalb dieser Arbeit;M. Laudien unterstützte und erhielt in den letzten 5 Jahren Unterstützung, Vortrags- und Beraterhonorare von: Olympus Deutschland GmbH, Olympus Europa SE & CO. KG, Novartis Pharma GmbH, Sanofi-Aventis Deutschland GmbH, Brainlab Sales GmbH, GlaxoSmithKline GmbH & Co. KG und der John Grube Foundation außerhalb der vorliegenden Arbeit.M. Gröger berichtet über Zuschüsse und Vortragshonorare von Sanofi, Novartis, AstraZeneca und GSK, außerhalb der eingereichten Arbeit.O. Pfaar berichtet über Zuschüsse und/oder Honorare von ALK-Abelló, Allergopharma, Stallergenes Greer, GlaxoSmithKline (GSK), HAL Allergy Holding BV/HAL Allergie GmbH, Bencard Allergie GmbH/Allergy Therapeutics, Lofarma, ASIT Biotech Tools SA, Laboratorios LETI/LETI Pharma, Anergis SA, SANOFI-AVENTIS, AstraZeneca, Zuschüsse von Biomay, Nuvo, Circassia, Inmunotek, und Honorare von MEDA Pharma/MYLAN, Mobile Chamber Experts (a GA2LEN Partner), Indoor Biotechnologies, Astellas Pharma Global, EUFOREA, Novartis, ROXALL, Procter&Gamble, IQVIA Commercial, Wort&Bild-Verlag, Verlag ME, WILEY&Sons, streamed-up! GmbH, RG Aerztefortbildung, Deutsche Fortbildungsgesellschaft für Hals-Nasen- und Ohrenärzte. Er ist Vorstandsmitglied/ExCom der Europäischen Akadamie für Allergologie und Klinische Immunologie (EAACI) und Mitglied des erweiterten Vorstandes der Deutschen Gesellschaft für Allergologie und Klinische Immunologie (DGAKI) und er ist/war eingebunden als Koordinator und/oder Mitglied/Autor verschiedener Leitlinien und Positionspapiere.A. S. Hoffmann erhielt Honorare von GSK, Sanofi und Novartis für Vorträge und Advisory Boards außerhalb dieser Arbeit.T. Hildenbrand berichtet über Vortragshonorare von AstraZeneca und Novartis außerhalb dieser Arbeit.R. Weber hat Honorare für Vortrags- und Beratungstätigkeit der Firmen GSK, Infectopharm, KARL STORZ SE & Co KG, NMP, Sanofi, Sidroga-Pharma und Stryker erhalten.W. Schlenter, S. Becker, T. Deitmer, H. J. Welkoborsky, S. Dazert, T. Huppertz, C. Bergmann, C.A. Hintschich, J. Zuberbier, C. Rudack, J. Gosepath, F. Klimek und I. Casper haben keine Interessenkonflikte im Zusammenhang mit der vorliegenden Arbeit., (Thieme. All rights reserved.)

Introduction  Probe-based confocal laser endomicroscopy (p-CLE) is a method for real-time in vivo visualization of mucosal changes on a cellular level. Due to the size of the endoscopes, it was mainly used in the gastrointestinal tract so far. First investigations on head and neck carcinoma described the oropharyngeal application. The further miniaturization of the laser probe now allows endonasal application and, thus, first experiences with the investigation of endonasal neoplasms. Objectives  The aim of the present investigation is to elucidate, based on the morphological criteria validated in the oropharynx, whether these criteria be transferred in a similar way to the endonasal mucosa. Methods  We conducted p-CLE (Cellvizio, Paris, France) with intravenous fluorescein staining in endoscopic sinus surgery in a patient with sinonasal inverted papilloma and a histologically confirmed squamous cell carcinoma. We compared the cellular visualization of pathological changes with those of healthy mucosa in the same specimen, and also with our former findings in the oropharynx. Results  Endonasal p-CLE proved to be quite feasible in the surgical setting, and the transfer of malignancy criteria in analogy to histological examination could be optically retraced. Furthermore, additional criteria for tissue dignity assessment were obtained. Conclusion  Our results suggest that endonasal application of p-CLE represents a valuable extension of the diagnostic repertoire available to date by an additional real-time analysis of the nasal mucosa. This is of particular value in surgically challenging anatomical areas such as the paranasal sinuses. Further investigation and validation will be necessary., Competing Interests: Conflict of Interests The authors have no conflict of interests to declare., (Fundação Otorrinolaringologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Objectives: Confocal laser endomicroscopy (CLE) is a method for real-time in vivo visualization of mucosal changes on a cellular level. First investigations on head and neck carcinoma described the oropharyngeal application. The aim of this investigation is to elucidate, based on the criteria validated in the oropharynx, whether these can be transferred to endonasal mucosa., Methods: CLE was performed with intravenous fluorescein staining in endoscopic sinus surgery in one patient with sinonasal inverted papilloma and another with squamous cell carcinoma. We compared cellular visualization of pathological changes to those of healthy mucosa in the same specimen as well to our former findings in the oropharynx., Results: Endonasal CLE proved to be well feasible in the surgical setting and the transfer of malignancy criteria in analogy to histological examination could be optically retraced. Furthermore, additional criteria for tissue dignity assessment were obtained., Conclusion: Our results suggest that endonasal CLE represents a valuable extension of the diagnostic repertoire available to date by an additional real-time analysis of nasal mucosa. This is of particular value in surgically challenging anatomical areas such as the paranasal sinuses. Further investigation and validation will be necessary., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Intraoperative definition of tumor free resection margins in head and neck cancer is challenging. In the current proof-of-principle study we evaluated a novel silica nanoparticle-based agent for its potential use as contrast enhancer. We synthesized silica nanoparticles with an average size of 45 nm and modified these particles with the fluorescence stain fluorescein isocyanate (FITC) for particle detection and with epidermal growth factor receptor (EGFR)-targeting antibodies for enhanced tumor specificity. The nanoparticles exhibited good biocompatibility and could be detected in vitro and in vivo by confocal laser scanning microscopy. Additionally, we show in an ex vivo setting that these modified nanoparticles specifically bind to tumor samples and could be detected using a handheld confocal fluorescence endomicroscope. From a clinical point of view, we believe that this method could be used for tumor border contrast enhancement and for better intraoperative definition of R-0 tumor resection.

Introduction: Ozone is a ubiquitous and irritant gas. We questioned whether an acute exposure to 0.2 ppm ozone impaired olfactory functioning., Methods: Healthy, normosmic subjects were exposed according to a parallel group design either to 0.2 ppm ozone (n = 15) or to sham (n = 13) in an exposure chamber for two hours. Possible irritating effects were assessed by questionnaire (range 0-5). The detection threshold of n-butanol was measured with the Sniffin' Sticks test before and after exposure. Olfactory thresholds were logarithmized and a two-way analysis of variance (ANOVA) with repeated measurements was carried out to test the effects of exposure (ozone vs. sham) and time (before vs. after exposure). Additionally, nasal secretions were taken at a preliminary examination and after exposure to determine interleukins 1ß and 8., Results: No irritating effects to the upper airways were observed. In the ozone group, the median score for cough increased from 0 to 2 at the end of exposure (sham group 0 and 0, respectively, p < 0.001). The ANOVA showed a main effect for ozone exposure (F (1, 26) = 27.6, p = 0.0002), indicating higher olfactory thresholds in the ozone group. Concentrations of interleukins in nasal secretions did not increase following ozone exposure., Conclusions: This study shows a clear impairment of olfactory functioning following an acute exposure to 0.2 ppm ozone., (Copyright © 2018. Published by Elsevier Inc.)

Background: Critical examination of the quality and validity of available allergic rhinitis (AR) literature is necessary to improve understanding and to appropriately translate this knowledge to clinical care of the AR patient. To evaluate the existing AR literature, international multidisciplinary experts with an interest in AR have produced the International Consensus statement on Allergy and Rhinology: Allergic Rhinitis (ICAR:AR)., Methods: Using previously described methodology, specific topics were developed relating to AR. Each topic was assigned a literature review, evidence-based review (EBR), or evidence-based review with recommendations (EBRR) format as dictated by available evidence and purpose within the ICAR:AR document. Following iterative reviews of each topic, the ICAR:AR document was synthesized and reviewed by all authors for consensus., Results: The ICAR:AR document addresses over 100 individual topics related to AR, including diagnosis, pathophysiology, epidemiology, disease burden, risk factors for the development of AR, allergy testing modalities, treatment, and other conditions/comorbidities associated with AR., Conclusion: This critical review of the AR literature has identified several strengths; providers can be confident that treatment decisions are supported by rigorous studies. However, there are also substantial gaps in the AR literature. These knowledge gaps should be viewed as opportunities for improvement, as often the things that we teach and the medicine that we practice are not based on the best quality evidence. This document aims to highlight the strengths and weaknesses of the AR literature to identify areas for future AR research and improved understanding., (© 2018 ARS-AAOA, LLC.)

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., (© 2016 ARS-AAOA, LLC.)

Aspirin exacerbated respiratory disease (AERD) has been defined as a non-steroidal anti-inflammatory drug (NSAID)-triggered hypersensitivity, non-allergic bronchial asthma and chronic rhinosinusitis (CRS) with nasal polyps. The underlying pathophysiology of AERD is not completely understood so far. An altered arachidonic acid metabolism and dysregulated enzyme activity are regarded to be causal. AERD is characterized by recalcitrant CRS with recurrent nasal polyps after sinus surgery, accompanied by difficult to treat bronchial asthma and adverse reaction after NSAID ingestion such as nasal blockage, itching, laryngospasm and severe asthma attacks. Affected individuals suffer from poor quality of life. Besides functional endoscopic sinus surgery, the application of topical and systemic steroids and symptomatic therapy, aspirin desensitization is the only causative treatment option. The diagnostic approach to AERD, the ideal desensitization protocol and especially the following daily maintenance dose is part of an ongoing debate. This article summarizes the current knowledge about the pathophysiology, focuses on modern diagnostic approaches of AERD and discusses various aspirin desensitization protocols with respect to efficacy as well as to undesirable side effects., (© 2016 S. Karger AG, Basel.)

Purpose: The German MAK value of methyl methacrylate has been fixed at 50 ppm. The aim of this study was to evaluate possible acute effects of an exposure to 50 ppm methyl methacrylate on the upper airways of human subjects., Methods: Twenty healthy subjects were exposed to 50 ppm methyl methacrylate and to air (sham) in an exposure chamber for 4 h according to a crossover design. Symptoms were assessed by the SPES questionnaire. Olfactory thresholds for n-butanol and mucociliary transport time were measured before and after exposure. Concentrations of interleukin 1ß and interleukin 8 were determined in nasal secretions taken after exposure. mRNA levels of interleukins 1ß, 6 and 8, tumor necrosis factor α, granulocyte-macrophage colony-stimulating factor, monocyte chemotactic protein 1, and cyclooxygenases 1 and 2 were measured in nasal epithelial cells, obtained after exposure. Possible effects were investigated by semiparametric and parametric crossover analyses., Results: The score of the item "irritation to the nose" was slightly elevated following exposure to methyl methacrylate (p ≤ 0.01). Olfactory functioning was not impaired. Mucociliary transport time did not change. Neither concentrations of interleukins in nasal secretions nor mRNA levels were elevated., Conclusion: Only minor irritating effects on the nose were observed. The acute exposure to 50 ppm methyl methacrylate did not cause any adverse effects. However, the results cannot be extrapolated to chronic exposure.

Introduction: The ingestion of foreign bodies is a frequently observed problem in daily clinical practice. In order to avoid complications such as perforation, endoscopic removal of potentially penetrating foreign bodies should be attempted quickly. The use of various endoscopic techniques has been reported for this purpose. However, extraction of foreign bodies from the mid gastrointestinal tract has rarely been reported., Case Report: We present the case of a patient who had swallowed a safety needle which could safely be removed from the jejunum by means of double-balloon enteroscopy (DBE). The combination of a thin p-type enteroscope with a thick t-type overtube was used in order to improve the manoeuvrability of the endoscope. The needle was pulled into the overtube which served as a protective shield during the retrieval of the endoscope., Conclusion: Our case report describes the potential of removing foreign bodies from the deep small bowel by pulling them into the overtube of a double-balloon enteroscope. If the suspicion of foreign body impaction in the small bowel is made, it may be advisable to primarily choose a balloon enteroscopy system. Through this, quick and deep insertion can be combined with a safe removal of the foreign body., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Delayed recovery after facial palsy results in aberrant nerve regeneration with symptomatic movement disorders, summarized as the postparalytic facial nerve syndrome. The authors present an alternative surgical approach for improvement of periocular movement disorders in patients with postparalytic facial nerve syndrome. The authors proposed that endoscopic brow lift leads to an improvement of periocular movement disorders by reducing pathologically raised levels of afferent input., Methods: Eleven patients (seven women and four men) with a mean age of 54 years (range, 33 to 85 years) and with postparalytic facial nerve syndrome underwent endoscopic brow lift under general anesthesia. Patients' preoperative condition was compared with their postoperative condition using a retrospective questionnaire. Subjects were also asked to compare the therapeutic effectiveness of endoscopic brow lift and botulinum toxin type A., Results: Mean follow-up was 52 months (range, 22 to 83 months). No intraoperative or postoperative complications occurred. During follow-up, patients and physicians observed an improvement of periorbital contractures and oculofacial synkinesis. Scores on quality of life improved significantly after endoscopic brow lift. Best results were obtained when botulinum toxin type A was adjoined after the endoscopic brow lift. Patients described a cumulative therapeutic effect., Conclusions: These findings suggest endoscopic brow lift as a promising additional treatment modality for the treatment of periocular postparalytic facial nerve syndrome-related symptoms, leading to an improved quality of life. Even though further prospective investigation is needed, a combination of endoscopic brow lift and postsurgical botulinum toxin type A administration could become a new therapeutic standard.

Correction of complex facial scars frequently requires individualized, multimodal strategies, which are composed of various therapeutic measures. This report provides information on techniques for correction of contractures, atrophic scars, scars within hair-bearing regions of the face and auricular keloids. Additionally, we present adjuvant procedures in a subject-related manner.

The German MAK value of 1-methoxypropanol-2 has been fixed at 100 ppm. The aim of this study was to evaluate possible acute effects of an exposure to 100 ppm 1-methoxypropanol-2 on the upper airways of human subjects. Twenty subjects were exposed in a crossover design to 100 ppm 1-methoxypropanol-2 and to air in an exposure chamber for 4h. Subjective symptoms were assessed by questionnaire. Olfactory thresholds for n-butanol and mucociliary transport time were measured before and after exposure. Concentrations of interleukin 1β and interleukin 8 were determined in nasal secretions taken after exposure. mRNA levels of interleukins 1β, 6 and 8, tumor necrosis factor α, granulocyte-macrophage colony-stimulating factor, monocyte chemotactic protein 1, and cyclooxygenases 1 and 2 were measured in nasal epithelial cells, obtained after exposure. Possible effects were investigated by semiparametric and parametric cross-over analyses. Subjects did not have any subjective irritating symptoms. The olfactory threshold was slightly elevated following exposure to 1-methoxypropanol-2. Mucociliary transport time did not change. Neither concentrations of interleukins in nasal secretions nor mRNA levels except for interleukin 1β were higher after exposure to 1-methoxypropanol-2. In conclusion, the acute exposure to 100 ppm 1-methoxypropanol-2 did not cause clear-cut adverse effects in test subjects., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

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 prospective double-blind placebo-controlled aspirin desensitization protocol with a maintenance dose of 100 mg daily. The primary outcome was polyp relapse after 36 months. Nasal endoscopy status, quality of life, and patients' symptom score as well as aspirin-related side-effects were monitored., Results: Due to the high dropout rate, only 31 individuals were evaluated. After 36 months, nasal polyp relapse was less frequent (P = 0.0785) and the polyposis score was lower (P = 0.0702) in the therapy group. Quality of life obviously improved (P = 0.0324), clinical complaints (P = 0.0083) were significantly reduced, and no severe aspirin-related side-effects were observed., Conclusion: Aspirin desensitization with a maintenance dose of 100 mg daily has a positive impact on nasal polyp relapse and seems to be a safe and suitable therapy to improve clinical complaints and the quality of life of individuals with AERD., (© 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.)

This article reports the case of a 14-year-old boy who was presented in the case conference with symptoms of decreased visual acuity, scintillating scotomas and photophobia. Physical examination revealed right facial paralysis, parotid gland swelling, high fever and poor general condition. Ophthalmoscopy revealed anterior and posterior uveitis including macular edema and chorioretinal infiltrates. Angiography revealed a dense pattern of hyperfluorescent lesions and these observations resulted in the diagnosis of Heerfordt syndrome. Under systemic prednisolone therapy, symptoms were reduced and visual acuity recovered.

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 patients with CRSwNP, and 30 from healthy controls of the inferior turbinate, were analyzed for their SPINK5 status. Genotypes of four SPINK5 single nucleotide polymorphism (SNPs; G1258A, G2475T, A2915G, and A1103G), as well as SPINK5 mRNA expression levels, were determined by polymerase chain reaction., Results: No correlation between any SPINK5 SNP and CRSsNP, CRSwNP, or allergies and asthma was observed. The heterozygous SNPs G1258A and A1103G were observed more frequently in aspirin-intolerant patients; the homozygous (A/A) genotype of SNP 1258 and the homozygous (G/G) genotype SNP 1103 were less frequent. There was no correlation between the analyzed SNPs and the level of SPINK5 expression. It was noted that in individuals with CRSwNP, aspirin intolerance, and allergies, SPINK5 expression was lowered., Conclusions: G1258A and A1103G polymorphisms are distinctive for the aspirin intolerance syndrome. Lowered SPINK5 expression might be a contributing factor leading to CRS, and appears to be characteristic for patients suffering from aspirin intolerance and from allergies., (Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.)

Objective: To use intraoperative confocal endomicroscopy for early detection and resection of squamous cell carcinoma (SCC) of the head and neck. A preliminary report., Design: Prospective case series., Setting: Tertiary referral hospital., Patients: Fifteen consecutive patients with SCC of the oral cavity, hypopharynx, and larynx were included from the Department of Otolaryngology-Head and Neck Surgery, HSK Dr Horst Schmidt Kliniken GmbH, Wiesbaden, Germany, Interventions: Confocal endomicroscopy was performed during diagnostic and therapeutic procedures with a prototype of a rigid laser endoscope in combination with the already available technology of autofluorescence., Main Outcome Measures: Real-time visualization of cellular and subcellular details during endoscopy. Diagnostic scores were applied to differentiate dysplastic and malignant mucosal changes of SCC of the head and neck from normal squamous cell mucosa using this method. Results were correlated with the well-established gold standard, histologic analysis., Results: Dysplastic and malignant changes of head and neck squamous cell mucosa were endoscopically determined by this unique in vivo application of confocal laser endomicroscopy using a rigid probe., Conclusions: We present preliminary and descriptive data using this novel technology in vivo. Considering the impact of a virtual real-time histologic analysis, this technology points to a very promising development. It may carry potential for quicker intraoperative diagnosis, less need for multiple frozen sections, and more precise resection margins.

BACKGROUND Trifunctional antibodies, such as catumaxomab (anti-EpCAM×anti-CD3) and ertumaxomab (anti- HER-2/neu×anti-CD3), transiently link immune effector cells to tumour cells, which results in cellular cytotoxicity towards the tumour cells. A functional immune system is therefore essential for effective anti-tumour activity. However, the commonly observed haematotoxicity of chemotherapeutics and radiation therapy may be associated with some degree of immunosuppression. Combining chemotherapy and trifunctional antibodies in cancer treatment requires understanding of the impact of chemotherapeutics on immune cell function and, thus, on the activity of trifunctional antibodies. METHODS The effect of chemotherapeutic treatment on trifunctional antibody-mediated anti-tumour activity was assessed in vitro. Blood samples were collected from 12 head and neck squamous cell carcinoma patients after chemotherapy (5-fluorouracil, cisplatin) and radiotherapy, and from one healthy control donor. The immune cell status was analysed and mononuclear cells (MNC) were isolated. The potency of catumaxomab and ertumaxomab was assessed in a cytotoxicity assay using MNC isolated from each patient sample in co-culture with a tumour target cell line. The release of infl ammatory cytokines was also monitored in the cell culture supernatant. RESULTS Most patients included in this study had decreased immune cell counts during the course of chemotherapy. Nonetheless, an effective and concentration-dependent anti- tumour activity mediated by trifunctional antibodies was demonstrated using these patient immune effector cells. The immune response activity of the patient immune cells was not impaired one week after cisplatin administration or even three days after the last 5-fluorouracil treatment. CONCLUSION This study shows for the first time that immune effector cells from cancer patients undergoing standard chemotherapy and radiotherapy can be activated by trifunctional antibodies for efficient killing of tumour cells.

Radiation therapy is a major therapeutic modality in the management of cancer patients. Over 60% of these patients receive radiotherapy at some point during their course of treatment and over 90% will develop skin reactions after therapy. Problematic wound healing in radiation-damaged tissue constitutes a major surgical difficulty and despite all efforts, irradiated skin remains a therapeutic challenge. This review provides an overview of the fundamental principles of radiation therapy with regards to the wound healing in normal and irradiated skin. Furthermore, it presents techniques that describe how to prevent and manage skin side effects as well as prospects that may improve cutaneous wound repair in general and in irradiated skin.

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, we analysed the potential association of GST-polymorphisms and chronic rhinosinusitis (CRS)., Methods: In total 170 nasal tissue samples, 49 tissue samples from patients with CRS without nasal polyps, 69 tissue samples from CRS with nasal polyps and 52 healthy tissue controls of the inferior turbinate were analysed for their individual GST-status. Genotypes for GSTM1 (null versus present), GSTT1 (null versus present), and GSTP1 (Ile105Val) were determined by Polymerase Chain Reaction. The respective genotypes were correlated to the incidence of CRS with and without nasal polyps in aspirin-tolerant and intolerant patients and to the individual health status concerning asthma and allergies., Results: No correlation between any GST-polymorphism and CRS with and without nasal polyps or allergies or asthma or aspirin-intolerance was observed., Conclusion: Our results do not suggest that there is a relevant genetic predisposition considering the individual GST-status for the susceptibility of nasal respiratory epithelia leading to CRS.

Confocal endomicroscopy is an emerging technique for intravital visualization of neoplastic lesions, but its use has so far been limited to the gastrointestinal (GI) tract. This study was designed to assess the feasibility of in vivo confocal endomicroscopy of different regions of the oropharyngeal mucosa and to evaluate different contrast agents. We examined five different regions of the human oropharynx in vivo, and images were collected in real time by using a confocal laser endoscope as formerly described for the GI tract. Additionally ex vivo specimens were examined using a topical contrast agent. Confocal scanning was performed at 488-nm illumination for excitation of exogenously applied fluorophores (topical acriflavine and intravenous fluorescein). Confocal endomicroscopy allowed for visualization of cellular and subcellular structures of the anterior human oropharyngeal region. Fluorescein staining yielded architectural details of the surface epithelium and also subepithelial layers. Images taken at increasing depth beneath the epithelium showed the mucosal capillary network. Acriflavine strongly contrasted the cell nuclei of the surface epithelium. The findings correlated well with the histology of biopsy specimens. This is the first report showing that the use of fluorescence confocal endomicroscopy represents a promising method to examine cellular details in vivo in different oropharyngeal regions in human.

Wound healing is a very complex process of interactions between different cells, growth factors, blood elements and extracellular matrix. Keloids represent one of the possible complications in the fundamental process of cutaneous wound repair. Despite all efforts, keloids remain a therapeutic challenge since no treatment is as yet considered 100% effective. Growth factors, discovered in the late 1970s, have been shown to influence dermal regeneration. However, the exogenous application of growth factors to chronic wounds has not proven to be effective in healing them. Additionally, genetic analysis has not revealed any single gene that might cause keloids; as such, classic gene therapy is not a feasible option for the treatment of keloids. A new approach is so-called somatic gene therapy. This review provides an overview of the fundamentals of wound healing and of keloids, and presents new possibilities that may improve cutaneous wound repair.

More and more patients with residual hearing on the contralateral side are becoming candidates for cochlear implants (CI) surgery due to increasing CI. The major benefits of regular binaural hearing are spatial hearing, localization, and signal source discrimination in both quiet and noisy surroundings. In most of the reports, hearing aid fitting was carried out without balancing both the devices. Twelve children and eight adults with residual hearing on the non-operated side were binaurally fitted. Our fitting procedure for the hearing aid was based on the desired sensation level [i/o] method. A loudness scaling was used to adjust the loudness perception monaurally and to balance the volume of both devices. Speech audiometry in quiet and noisy surroundings was conducted both monaurally and in the bimodal mode. The fitting was modified according to the respective test results. In all children and six adults, a measurable gain and/or a subjective improvement of speech perception was achieved. Two adult patients did not accept the new fitting. In seven younger children, loudness scaling was impossible to perform because of age. This was also the case with speech audiometry for two children. A structured bimodal fitting using loudness scaling for both the cochlear implant and the hearing aid results in a subjective and objective amelioration of the patient's hearing and speech perception.

Orbital decompression and, in some cases, decompression of the optic nerve are the principal surgical procedures used for treatment of moderate or severe Graves' orbitopathy (GO). Histological examination of the surgical specimens of the ethmoid revealed a wide spectrum of inflammatory mucosal changes. The charts of 68 GO patients (55 female and 13 male; age range: 14 - 85 years) were retrospectively reviewed. Lund - Mackay scores were calculated for each patient based on findings of pre-operative computer tomography (CT) sinus scans, and the incidence of histological changes associated with polypoid and eosinophilic inflammation was assessed. Files did not reveal any evidence of chronic rhinosinusitis with or without nasal polyps based on endoscopic findings. Sinus opacification on CT (of any extent) was found in 20 out of the 68 patients (29.4%). On histological exam, histological changes of the sinus mucosa indicative for chronic rhinosinusitis were found in 31 out of the 68 GO patients (45.5%). A histological examination of the sinus mucosa indicative for chronic polypoid inflammation was present in 25 patients. Fourteen out of these 25 patients showed mucosal tissue eosinophilia on histology. Six patients had mucosal changes suggesting chronic non-polypoid inflammation with tissue eosinophilia on histological exam. The incidence of chronic rhinosinusitis in individuals without GO ranges between 10 and 15%. The incidence of histological changes of the sinus mucosa indicative for chronic rhinosinusitis described in this investigation suggests that chronic inflammatory disease is considerably more frequent in GO patients, when compared to the incidence of chronic rhinosinusitis in individuals without GO. Additionally, our data underline that CT imaging of the paranasal sinuses underestimates (29.4%) the incidence of inflammatory changes of the sinus mucosa (45.5%) of any extent in GO patients.

Objective: German MAK value of acetaldehyde has been fixed at 50 ppm to prevent from irritating effects. The threshold value is mainly based on animal experiments. The aim of this study was to evaluate acute effects of an exposure to 50 ppm acetaldehyde on the upper airways of human subjects., Methods: Twenty subjects were exposed to 50 ppm acetaldehyde and to air in an exposure chamber for 4 h according to a crossover design. Subjective symptoms were assessed by questionnaire. Olfactory threshold for n-butanol and mucociliary transport time were measured before and after exposure. Concentrations of interleukin 1beta and interleukin 8 were determined in nasal secretions taken after exposure. mRNA levels of interleukins 1beta, 6 and 8, tumour necrosis factor alpha, granulocyte-macrophage colony-stimulating factor, monocyte chemotactic protein 1, and cyclooxygenases 1 and 2 were measured in nasal epithelial cells, gained after exposure. Possible effects were investigated by semiparametric and parametric crossover analyses., Results: Exposure to acetaldehyde did not cause any subjective irritating symptoms. Olfactory threshold did not change. Mucociliary transport time increased insignificantly after exposure to acetaldehyde. Neither concentrations of interleukins in nasal secretions nor mRNA levels of inflammatory factors were higher after exposure to acetaldehyde., Conclusion: An acute exposure to 50 ppm acetaldehyde did not cause any adverse effects in test subjects.

Objective: Our aim was to present a failure analysis after cochlear implant revision surgery in a large series of children and adults and to assess the outcome and audiologic performance., Methods: Fifty-six cochlear implant failures that occurred in 422 devices implanted between 1990 and 2007 at the Department of Otolaryngology, Head and Neck Surgery at the University of Mainz, Germany, were retrospectively analyzed. The causes of failure were reviewed evaluating the individual history, telemetric and intraoperative findings and manufacturer's investigation reports., Results: We performed 56 surgical revisions in a series of 422 consecutive implants (overall revision rate: 13.27%). The most frequent causes for revision were hard failures (58.9%), most commonly caused by traumatic impact (37.5%), especially in the pediatric population. Soft failures were less frequent (21.4%). Surgical reimplantations, although challenging in some cases, were performed without complications and with an electrode insertion depth comparable to that at the time of the initial implantation in all patients. The average audiologic performance improved by 2.4 dB in pure-tone perception levels after reimplantation., Conclusion: The cochlear implant failure rates vary between children and adults as well as between different implant manufactures. However, cochlear reimplantation is safe with excellent and predictable results in audiologic performance.

Purpose: To evaluate whether ApneaGraph (AG) and polysomnography (PSG) deliver comparable results in patients with sleep-related breathing disorders., Procedures: A prospective study was performed, which included 14 patients with obstructive sleep apnea syndrome. Apnea-hypopnea index (AHI), hypopnea index (HI), apnea index (AI), obstructive, central and mixed apnea, oxygen saturation (SaO2), pulse and body position were simultaneously assessed by PSG and AG in each individual., Results: There was a good correlation between measurements of AG and PSG for AHI, pulse, SaO2, body position and central apnea. However, our study showed differences between PSG and AG for AI (p = 0.002), HI (p = 0.013), mixed apnea (p = 0.003) and obstructive apnea (p = 0.013). AG indicated that 2/14 patients had a pure upper airway obstruction, 6/14 patients had a predominance of lower obstruction and 6/14 patients had a predominance of upper obstruction., Conclusion: AG provides comparable results for AHI, pulse, SaO2, body position and central apnea when compared to PSG, but not for the rest of the measurements. Using AG, the distribution of sites of obstructive events could be identified in this study in all of the patients., (Copyright 2008 S. Karger AG, Basel.)

The predictive value of cadherin-11, tenascin, fascin, and mucin-1 as markers for the likelihood of recurrence in pleomorphic adenoma of the parotid gland was examined. In this retrospective study we analysed 20 tumours from16 patients by immunohistochemistry. Staining intensities were measured using a semiquantitative scoring approach; localisation (tumour centre vs border) as well as clinical data were analysed and correlated with follow-up. Cadherin-11 was increased in recurrent tumours. However, no changes of fascin, tenascin or mucin-1 were observed. Cadherin-11 and fascin were increased in primary tumours of patients with later recurrence, with fascin upregulation restricted to the tumour border. In conclusion, cadherin-11 and fascin should be further analysed for their value as markers for later recurrence in pleomorphic adenoma. Our observations might reflect dysregulation of cellular pathways contributing to cellular dissemination, which might potentially result in later recurrence.

Conclusions: Our findings emphasize the role of a thorough diagnostic evaluation preoperatively and a targeted long-term medical therapy following any sinonasal surgery for inflammatory disease. Early onset of long-term aspirin desensitization can address a very predominant inflammatory stimulus in a large number of our patients in an effort to prevent recurrent chronic rhinosinusitis (CRS) after successful surgical therapy., Background: Postoperative recurrence of CRS, regardless of the ongoing evolution of diagnostic and surgical techniques, still poses an unsolved problem., Subjects and Methods: This investigation was designed to further characterize the role of aspirin intolerance (AI) and inhalant allergies as persistent inflammatory stimuli in the postoperative period and secondly to analyze the correlation between preoperative computed tomographic (CT) scores and the actual intraoperative findings. A total of 143 patients with recurrent CRS were included in this retrospective analysis, who all underwent revision sinus surgery at our institution after one or multiple previous operations. Charts were analyzed for the incidences of AI and inhalant allergies, CT scores, and intraoperative scores., Results: In all, 66/143 patients had inhalant allergies and 55/143 were diagnosed with AI. The risk of recurrent CRS was found to be highest in the group with AI, along with the shortest interval between previous surgical interventions and the need for revision. In a subgroup of 34 cases, correlations between CT and intraoperative endoscopy scores were poor in 79%. Interestingly, at the time of recurrence the frontal sinuses were diseased in 17.6% of cases, where they had been healthy at the time of the initial intervention.

To evaluate the impact of 1-methoxypropanol-2 (MEP) for the stimulation of an inflammatory response in human respiratory mucosa, we exposed 22 primary cell cultures of nasal respiratory epithelia of healthy individuals to MEP concentrations at the level of the German MAK-value (100 ppm) and to the 10-fold concentration (1000 ppm). After 4 and 24h we analyzed the transcription of TNF-alpha, IL-1beta, IL-6, IL-8, MCP-1, GMCSF, Cox-1 and Cox-2 by quantitative PCR as well as the release of the respective cytokines by ELISA. At both MEP concentrations we observed a significant increase of TNF-alpha-, IL-1beta-, IL-6- and Cox-2-transcripts after 4h. After 24h cytokine transcription of TNF-alpha, IL-1beta and IL-6 was normalized, but Cox-2 remained elevated. On the protein level IL-1beta as well as granulocyte macrophages colony stimulating factor (GM-CSF) were decreased after 4h or 24h and uniquely IL-8 levels were increased after 4h. Our data suggest that MEP induces the transcription of genes encoding proinflammatory cytokines and mediators but largely not translation of those. Considering these in vitro data, existing exposure limits seem to be safe with respect to inflammatory responses of the upper respiratory tract. However, the effects of long-term exposures to MEP should be watched closely.

There is increasing evidence of an angiogenic response of irradiated tumors resulting in decreased radiation sensitivity. However, little is known about the contribution of tumor vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF)-release induced by irradiation to the individual level of resistance. In this in vitro study, we analysed the VEGF- and bFGF-release of six epithelial tumor cell lines before and after irradiation and correlated these data to the corresponding irradiation resistance. Two head and neck squamous cell carcinoma (HNSCC), two renal cell carcinoma (RCC), and two ovarian cancer (OC) cell lines were each exposed to 2 or 6 Gy single dose using a 137Cs-source. Non-irradiated controls were processed in parallel. Survival rates were assessed by colony assays as a measure of resistance. The released VEGF and bFGF was quantified by ELISA assays. Additionally, the expression of VEGF and its respective receptors (FLK, FLT, and NRP1) was visualized by immunohistochemistry. VEGF-release was significantly increased (p<0.05) in all cell lines after irradiation. Release was most prominent in the RCC cell lines, less in the HNSCC cell lines and lowest in the OC cell lines. Radiation resistance correlated to the absolute level of released VEGF after irradiation as well as to its relative increase (r>0.9, p<0.01). bFGF levels were not correlated to resistance. VEGF and all three VEGF-receptors were detected in all cell lines analyzed supporting the concept of an autocrine protective mechanism. We suggest that tumor cell survival after irradiation may be enhanced by released VEGF and that the level of released VEGF directly corresponds to the resistance of the tumor to irradiation.

Background: Postoperative bleeding is the major complication in tonsillectomy, and pain the most common side effect. The use of bipolar scissors versus blunt dissection tonsillectomy were compared in this study in order to evaluate postoperative bleeding and pain, as well as operative time., Methods: In this case control study, 138 patients with the diagnosis of chronic tonsillitis, mononucleosis or a peritonsillar abscess were divided into two groups. A total of 78 patients were operated using bipolar scissors while 60 patients underwent tonsillectomy by blunt dissection. Operating time, frequency of postoperative bleeding and the postoperative pain score were compared between these two groups., Results: The average operating time in the bipolar scissor group showed a tendency to be shorter than in the blunt dissection group (mean 4.1 min), although this did not reach a level of statistical significance. No differences were seen in pain scores or in the incidence of postoperative bleeding., Conclusion: The data documented in this study show that tonsillectomy with bipolar scissors might represent a surgical option to reduce surgical time in a larger patient group. Postoperative pain and the incidence of postoperative bleeding did not show any statistical difference between the two surgical techniques.

Background: Methyl methacrylate (MMA) has been reported to cause histopathological changes in rodent nasal epithelium after inhalation challenges. Data in humans are lacking., Methods: In this in vitro design 22 primary cell cultures taken from inferior turbinate tissue of healthy individuals were exposed to MMA concentrations of 50 ppm (German MAK-value) and 200 ppm. mRNA expression and cytokine release of inflammatory mediators were quantified after 4h and after 24h. Controls were exposed to synthetic air. Q-PCR analysis was performed for TNF-alpha, IL-1beta, IL-6, IL-8, MCP-1, GMCSF, Cox-1 and Cox-2. ELISA assays were performed from culture supernatants for TNF-alpha, IL-1beta, IL-6, IL-8, MCP-1 and GMCSF., Results: Acute inductions of mRNA after 4h were observed for TNF-alpha, IL-1beta, IL-6, IL-8 and MCP-1 at 50 ppm. ELISA analysis of the described parameters did not reveal any significant upregulations at both concentrations after both 4h and 24h., Conclusions: The obtained data suggest that exposure of human respiratory epithelia in vitro to 50 ppm and to 200 ppm of MMA does not induce lasting upregulation of the inflammatory mediators measured in this study. The exposure limit of 50 ppm appears safe following these results obtained from human respiratory epithelia.

Juvenile nasopharyngeal angiofibroma (JNA) is a rare benign tumor, mostly affecting adolescent males. Some patients develop recurrences after surgery independently of completeness of removal. Only very limited data concerning underlying chromosomal changes are available. We therefore analyzed samples of 22 JNAs, including six recurrences, with comparative genomic hybridization (CGH). Additionally, quantitative image cytometry was used for measurement of DNA aneuploidy in representative samples. Of the 13 primary JNAs without later recurrence, DNA gains were identified on autosomes in only two samples. Four patients with one or two recurrences were included in the study; for one of these, no material of the primary tumor was available for analysis. Looking at autosomes, two of the three available primaries displayed multiple gains; in one of those, two additional losses were observed. Multiple gains were detected in two of the four first recurrences, but none in the two second recurrences. Across all 22 samples, gains occurred in more than one sample on chromosomes arms 1p, 9q, 10q, 12q, 16p, 16q, 17q, 19p, 19q, 20q, and 22q. Losses were found in a single case exclusively on chromosome 4. Sex chromosomes were frequently affected in both primary tumors and recurrences. There was no correlation among tumor staging, age, and DNA amplification. No DNA aneuploidy was detected, a finding in accordance with the generally benign characteristics of JNAs. Our observations suggest that in JNA the activation of oncogenes is more likely than the inactivation of tumor suppressor genes. Autosomal gains in the primary tumor should be further evaluated as markers for a potentially increased risk of recurrence after surgical removal in this entity.

This retrospective analysis reflects the outcome of various techniques used in a series of 41 cases of choanal atresia treated at the Department of Otoloaryngology, Head- and Neck Surgery at the University of Mainz between 1980 and 2006. Thirteen bilateral and 28 unilateral cases are included. After endonasal management in 38 and a transpalatine approach in 3 cases a total of 15 patients needed revision surgery between 1 and 5 times to establish a stable result. Postoperative stenting was used in 23 patients with a failure rate of 35%, whereas only 11% of the 18 patients without stenting had to be revised. None of those 5 cases where Mitomycin C had been applied intraoperatively in combination with postoperative transnasal dilations needed surgical revision. We conclude that the endonasal micro-endoscopic surgical approach is successful if combined with postoperative dilations for up to one year. Stenting should be abandoned as it stimulates granulation formation that frequently leads to restenosis. The intraoperative application of Mitomycin C offers a promising adjunct in achieving a stable

Acetaldehyde has been shown to be cytotoxic and carcinogenic to the upper respiratory tract epithelium of rodents following long-term exposure. Most animal studies have concentrated on carcinogenicity and DNA-protein cross-link formation, while less is known about potential dose- and time-dependent induction of aldehyde-induced rhinitis in humans. In this in vitro study, 22 primary cell cultures established from inferior turbinate tissue of healthy individuals were exposed to acetaldehyde concentrations of 50 (German MAK value) or 500 ppm for 4 or 24 h. mRNA expression and protein levels of cytokines and other inflammatory mediators were quantified at the end of the 4- and 24-h exposures. Controls were exposed to synthetic air. Quantitative polymerase chain reaction (Q-PCR) analysis was performed for interleukin (IL)-6, IL-8, IL-1beta, monocyte chemotactic protein (MCP)-1, tumor necrosis factor (TNF)-alpha, GMCSF, Cox-1, and Cox-2. Enzyme-linked immunosorbent assay (ELISA) was performed from culture supernatants for IL-6, IL-8, IL-1beta, MCP-1, TNF-alpha, and GMCSF. Significant inductions of IL-1beta, TNF-alpha, and Cox-1 and Cox-2 mRNA were observed following exposure to > or =50 ppm acetaldehyde for 4 h. IL-6 and MCP-1 were also induced following a 4-h exposure to 500 ppm acetaldehyde. For all these parameters, effects were significantly stronger at the higher concentration. After 24-h of exposure only Cox-2 remained significantly elevated at 500 ppm but not at 50 ppm, while all other mediators had been downregulated. The obtained data suggest that with exposure to 500 ppm and remarkably also at the level of the occupational exposure limit of 50 ppm, an immediate transient upregulation of inflammatory mediator mRNA is induced, possibly leading to subclinical inflammatory effects.

Introduction: Different causative mechanisms of ophthalmic complications during endonasal sinus surgery have been reported. Only a few cases of blindness caused by affections of the optic nerve due to inflammatory paranasal sinus disease have been described., Objective: Inflammatory optic neuropathy shall be considered among the causative factors for amaurosis after sinus surgery., Material: We present two patients with dramatic visual decrease occurring two weeks after sinus surgery as a result of inflammatory posterior paranasal sinus disease., Results and Conclusion: Our therapy including surgical intervention in form of orbital or optic nerve decompression accompanied by systemic steroids and antibiotic therapy resulted in a significant increase of visual acuity in one case and a complete restoration of vision in the other case. In these two cases surgical intervention in the described fashion along with systemic steroids and antibiotic therapy represented a successful therapeutical approach.

We analyzed tumor and surrounding mucosal samples of head and neck squamous cell carcinoma by fragment analysis for gain of genomic material as a potential indicator for oncogenic transformation. Our aim was to evaluate the potential value of this fast and sensitive polymerase chain reaction (PCR)-based method for intra-operative detection of chromosomal aberrations as a surrogate marker for incomplete tumor resection. Biopsies of the primary tumors and adjacent macroscopically nonmalignant mucosa 1 and 2 cm away from the tumor margins were collected from 20 patients. DNA were isolated, and 11 microsatellite markers at loci 3q25.31 approximately 3q28 were amplified by PCR. Allelic losses or gains were analyzed by capillary electrophoresis. Imbalanced alleles were common in the samples evaluated. In the median gains of the informative loci were detected in 67% of the primary tumors, 22% of the samples taken at 1 cm and 15% of the samples taken at 2 cm distance. We observed gains of 3q at least in one microsatellite in all primary tumors, in 15 (1 cm) and 12 (2 cm) nonmalignant mucosa samples. Gain of genetic material is frequent in tumor-surrounding mucosa. Detection of small chromosomal aberrations is possible using the PCR-based, highly sensitive, and fast-to-perform fragment analysis technique. The value for the diagnosis and prognosis will have to be proven in follow-up studies.

Aim: Ultrasound (US) is a cost effective and time saving examination method for diseases of the neck,and can be used without any known side effects or limitations. US tied into modern navigation devices may significantly improve intraoperative orientation in regions with soft tissue characteristics., Methods: 22 patients with soft tissue tumours of the head and neck underwent surgical procedures assisted by CAS system LandmarX (Medtronic) in combination with the US system DynaVievP II (Aloka). Clinical feasibility of using intraoperative US in navigated surgical procedures has been investigated by paying particular attention to the surgical approach, possible interferences from surgical instruments and time consumption., Results: In the case of soft tissue shift, US can provide a sequence of a section of the operative field and, without delay, an instant comparison with the preoperative imaging data set. The feasibility of using this method is severely limited by the additional preparation required, the unfamiliar handling during surgery, and design-related matters., Conclusions: Integrating US into a navigation device could provide additional useful information for a more controlled resection of soft tissue disease of the neck and below the base of the skull.

Background: Minimally invasive techniques have been described for cochlear implant surgery, but so far this had not been the case for Med-EL devices., Objective: To describe a newly developed minimal access approach for the implantation of Med-EL devices and report our results after up to 1 year of follow-up in 52 patients., Discussion: The use of a minimally invasive approach without raising a flap or extensive drilling of a bony well was feasible in all 52 patients of this series. It shortened the surgical time to an average of 45 min and there were no specific postoperative complications. The average follow-up of 8.4 months was uneventful with the implants well covered and fixed in their position. The described approach therefore appears to be a safe, time- and cost-effective alternative to the standard procedure in cochlear implant surgery using Med-EL devices.