Zusammenfassung Hintergrund Das Plattenepithelkarzinom des Naseneingangs (Vestibulum nasi) ist eine sehr seltene Tumorentität. In der Konsequenz herrscht bezüglich der Ätiologie, des Stagings und der notwendigen Therapie dieser Tumoren nach wie vor Uneinigkeit. Insbesondere die Mitbehandlung regionaler Lymphknotenstationen ist Gegenstand wissenschaftlicher Diskussionen. Methode Alle via Pubmed gefundenen Artikel zum Thema wurden hinsichtlich folgender Themenschwerpunkte untersucht: Lymphatische Versorgung, Metastasierung, Inzidenz, Prognose, Risikofaktoren (Leder, Nickel, Nikotin, Humane Papillomaviren), Tumorklassifikationssystem (UICC-, AJCC-, Wang-Klassifikation), Therapie des Primärtumors, Therapie regionaler Lymphknoten und Immunhistochemie. Ergebnisse Im vorliegenden Übersichtsartikel wurden 55 Veröffentlichungen ausgewertet. Die Ergebnisse hinsichtlich der untersuchten Aspekte sind in sich inhomogen. Schlussfolgerungen Als Klassifikationssystem wird die Wang-Klassifikation empfohlen. Für die Behandlung kleinerer Tumoren (T1-T2-Wang) kommen operative Resektionen oder Bestrahlungen in Betracht. Größere Tumoren (T3-Wang) sollten reseziert und einer adjuvanten Bestrahlung zugeführt werden. Im Falle einer cT1-cT2cN0-Situation kann – eine dezidierte bildgebende Diagnostik vorausgesetzt – auf eine elektive Therapie der regionalen Lymphknoten verzichtet werden.

Background Sudden sensorineural hearing loss (SSHL) is a disease, which severely affects the patient’s social and relational life. The underlying pathomechanisms have not been finally clarified yet and outcome is not predictable. Methods We conducted a retrospective study in order to identify parameters that influence hearing recovery. The data base contains results of basic otoneurological tests and clinical parameters of 198 patients with idiopathic SSHL of at least 60 dB in at least four frequencies, diagnosed and treated at the University Hospital of Münster, Germany, between 1999 and 2015. Hearing recovery was measured by pure tone audiometry. Results Multivariate linear and logistic regression analyses indicate that the chance as well as the magnitude of hearing recovery is higher for patients with normal caloric testing than for patients with pathological caloric testing. However, for the subgroup of patients who attained a hearing recovery, the caloric testing result was not found to influence the magnitude. Instead, the magnitude was noticeably lower for patients within this subgroup who had a previous hearing loss. Furthermore, we found indications that the magnitude is higher for men than for women and that receiving a high-dose steroid therapy is associated with a higher chance and magnitude of a hearing recovery. Conclusions We conclude that SSHL associated with disorders of the vestibular system or previous hearing loss represent special sub-entities of SSHL that may be caused by unique pathophysiological mechanisms and are associated with worse outcome. Furthermore, our data support the importance of elevated dosage of steroids in SSHL therapy.

Sarcoidosis, a chronic, inflammatory disease that affects various different organs, is characterized by noncaseating epitheloid granulomas. This systemic inflammatory process is associated with an increased risk of cancer. Several cases of sarcoidosis that mimic metastatic tumor progression in radiological findings have been reported so far. However, there are also cases that have presented a coexistence of sarcoidosis and metastasis, which have caused a diagnostic and therapeutic dilemma. Due to inadequate current therapies, a reliable differentiation between benign and malignant lesions is crucial. This review focuses on the residual risk of the coexistence of metastases within radiological suspicious lesions in patients with a history of solid tumors and sarcoidosis, as well as immunological findings, in order to explain the potential associations. Sarcoidosis has the potential to promote metastasis as it includes tumor-promoting and immune-regulating cell subsets. Notably, myeloid derived suppressor cells may serve a pivotal role in metastatic progression in patients with sarcoidosis. In addition, the present review also evaluates the potential novel diagnostic approaches, which may be able to differentiate between metastatic lesions and sarcoidosis. The risk of coexistent metastasis in sarcoidosis lesions must be considered by clinical practitioners, and a multidisciplinary approach may be required to avoid misdiagnosis and the subsequent unnecessary surgery or insufficient treatments.

Background. Health-related quality of life (HRQOL) has received more and more attention as an outcome in cancer therapy. In this exploratory study, we assessed the long-term HRQOL among 77 surgically treated patients with parotid gland cancer.Methods. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30-questions (EORTC-QLQ-C30) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Head and Neck 35-questions (EORTC-QLQ-C30-H&N35) questionnaires were used in a cross-sectional design. The mean time-lag between initial diagnosis and completion of the questionnaire was 89.7 months.Results. The HRQOL significantly increased with the time-lag to surgery and decreased with the patients' age. Factors with clinically significant effects in several areas of long-term HRQOL (ie, more than 4 scores) were age, type of neck dissection, preoperative facial nerve palsy, and postoperative radiation therapy.Conclusion. In parotid gland cancer surgery, factors, such as sex, age, type of surgery, facial nerve palsy, and radiation therapy, seem to be associated with clinically meaningful differences in long-term HRQOL scores. (C) 2015 Wiley Periodicals, Inc.

OBJECTIVETo compare the outcome of hearing rehabilitation in younger versus older adult cochlear implant recipients. Analysis of surgical and postoperative complications, as well as the number of auditory therapy sessions in the two age groups.STUDY DESIGNIndividual retrospective cohort study.METHODSA cohort of 145 postlingually deafened adults was evaluated in this study. The patients were divided into two age groups based on the age at implantation: Group I, 18 to 69 years; and Group II, 70 and older. Postoperative hearing performance was measured based on the German Freiburg monosyllabic word test (FM) and the Oldenburg sentence test (OLSA).RESULTSPostoperative hearing evaluation results in both groups plateaued and remained constant after 12 months of implantation. The results remained constant at the 2 and 3-year time intervals. There was a significant difference in complications arising after cochlear implantation. Group II showed more cases of vertigo and dysgeusia. The number of auditory therapy sessions in both groups was similar.CONCLUSIONCochlear implantation in the elderly is highly effective; the postoperative hearing performance is at the same level as younger adult recipients. Complex hearing tasks, such as hearing in background noise, requires an equally long time for comprehension. The recovery period of vestibular dysfunction after surgery may be longer in the elderly. Auditory therapy rehabilitation is not more time consuming in the elderly compared with the younger counterparts.

IMPORTANCE Electrophysiologic facial nerve monitoring is becoming an established intraoperative aid to assist the surgeon in facial nerve trunk or branch location and dissection. Limited studies have addressed the postoperative outcomes of parotid surgery with and without monitoring. OBJECTIVE To examine the influence of intraoperative facial nerve monitoring on postoperative facial nerve function and procedure duration in parotid surgery. DESIGN, SETTING, AND PARTICIPANTS An 8-year retrospective review of parotidectomies performed at the Department of Otorhinolaryngology-Head and Neck Surgery, University of Münster. The study analyzed 120 patients undergoing parotidectomy without monitoring from January 1, 1988, to December 31, 1991, and 147 patients undergoing parotidectomy with monitoring from January 1, 2003, to December 31, 2006. The patients were further subdivided in partial parotidectomy (PP) (n = 222) and total parotidectomy (TP) (n = 45) groups. An evaluation of operative time was performed to test the hypothesis of shorter duration of surgery with facial nerve monitoring. Final follow-up was completed on December 31, 2008, and data were analyzed from June 1 to December 31, 2013. MAIN OUTCOMES AND MEASURES Comparison of the incidence of facial nerve dysfunction and operative time between the PP and TP subgroups with and without monitoring. RESULTS A total of 267 patients (127 men [47.6%] and 140 women [52.4%]; mean [SD] age, 51.3 [17.6] years; range, 3-90 years) were included in the analysis. A significant reduction in postoperative facial nerve dysfunction with the use of nerve monitoring could be seen in the PP group (46 of 99 without monitoring [46.5%] vs 18 of 123 with monitoring [14.6%]; P = .001). A similar finding was evident in the TP group when comparing moderate and severe nerve dysfunction (9 of 21 without monitoring [42.9%] vs 2 of 24 with monitoring [8.3%]; P = .01). The mean (SD) operative time in the PP subgroup without nerve monitoring was 115.3 (37.8) minutes; with nerve monitoring, 110.1 (33.6) minutes. The mean (SD) operative time in the TP subgroup without nerve monitoring was 134.5 (50.4) minutes; with nerve monitoring, 158.3 (56.3) minutes. There was no statistical difference between these groups. CONCLUSIONS AND RELEVANCE Facial nerve monitoring in primary parotid surgery for benign and malignant disease does not necessarily reduce the operative time, but the rate of transient postoperative facial nerve dysfunction or the grade of palsy is reduced.

The objective of this study is to analyze the accuracy of computed tomography in detecting malignant thyroid cartilage invasion. In a retrospective chart review, 120 patients with carcinoma of the larynx and hypopharynx underwent computed tomography before total laryngectomy. These data were compared with the histological specimens. Multidetector computed tomography (MDCT) scan had a positive predictive value (PPV) of 76 % and a negative predictive value (NPV) of 69 %. The specificity of MDCT was 89 % and sensitivity was 46 %. Comparison between radiologic suspected cartilage invasion and histologic results showed a significant correlation (p < 0.02). We found no significant impact of cartilage invasion concerning survival rates (5-year overall survival p = 0.683; 5-year disease-free survival p = 0.711). Preoperative CT scan is an important instrument in detecting neoplastic cartilage invasion.

Objectives/Hypothesis External auditory canal cancer is rare and carries a poor prognosis. To date, only a few studies provide evidence for clinical decision making in multimodal treatment. Methods Retrospective chart review of 36 cases in three tertiary referral centers. Results Thirteen patients were treated by surgery alone, 18 by surgery with adjuvant chemoradiotherapy (CRT) and five by primary CRT. Clear surgical margins (R0) were obtained in 19 patients and positive margins (R1) in 12. The 5‐year overall survival and local control rates were 59.4% and 74.2% with R0 status versus 56.6% and 26.3% with R1 status. The 5‐year overall survival and local control rates were 46.2% and 70.7% with surgery alone, 78.1% and 43.2% with surgery and adjuvant CRT, and 25.0% and 80.0% with primary CRT. Conclusion Surgery is integral to the management of external auditory canal cancer, whereas CRT is necessary as an adjuvant or primary treatment, depending on tumor stage. Level of Evidence 4. Laryngoscope , 125:2107–2112, 2015

The aim of this study was to compare audiometric results before and after stapes surgery and identify potential prognostic factors to appropriately select patients with otosclerosis who will most likely benefit from surgery. We enrolled 126 patients with otosclerosis (162 consecutive ears) in our study who underwent stapes surgery between 2007 and 2012 at our institution. Preoperative and postoperative data including pure-tone audiometry, speech audiometry, stapedial reflex audiometry and surgical data were analyzed. The average preoperative air-bone gap (ABG) was 28.9 ± 8.6 dB. Male patients and patients older than 45 years of age had greater preoperative ABGs in comparison to females and younger patients. Postoperative ABGs were 11.2 ± 7.4 dB. The average ABG gain was 17.7 ± 11.1 dB. Preoperative audiometric data, age, gender and type of surgery did not influence the postoperative results. Stapes surgery offers predictable results independent from disease progression or patient-related factors. While absolute values of hearing improvement are instrumental in reflecting audiometric results of a cohort, relative values better reflect individual’s audiometric data resembling the patient’s benefit.

Carcinoma in cervical lymph nodes of unknown origin represents a rare clinical entity where optimal diagnostic and therapeutic management is still a widely debated issue. Molecular classification of these metastases is thus of utmost importance. We analyzed the expression of eight basic molecular markers in 26 metastases from unknown primaries, 31 metastases from overt primaries and their associated primaries. Medical records of the respective patients were reviewed for main clinicopathological parameters. The expression rates showed no significant differences between the two tumor entities, neither in absolute terms nor in comparison among the parameters. Surprisingly, patients with metastases from unknown primary demonstrated improved progression-free survival (p = 0.046) despite advanced age (p = 0.029), advanced nodal stage (p = 0.006) and higher incidence of extracapsular spread (p = 0.045) compared to patients with metastases from overt primaries. Presence of extracapsular spread was associated with increased expression of epidermal growth factor receptor in metastases from overt primaries (p = 0.035) and reduced expression of matrix metalloproteinase-2 in metastases from unknown primary (p = 0.031). We thus conclude that cervical metastases from unknown and overt primaries show similarities in their molecular profile, but fundamental differences in clinical parameter.

Recurrent laryngeal papillomatosis (RLP) is, although benign, a challenging disease for both, the patient and the treating physician. Maximum disease control with minimum intervention is considered to be the gold standard. However, patients have to undergo repeating surgical interventions. Human papillomavirus (HPV), mainly so called low risk types, are thought to be responsible for the development of RLP. But, there is still some controversy over the true prevalence of HPV and the virus-specific molecular diagnostic of choice. Therefore archival tissue samples from 44 patients with RLP at laryngeal site, out of which eight developed laryngeal cancer, was screened for presence of HPV through various molecular approaches. Results from these different methodologies were compared between each other and with patient's characteristics. The overall detection rates of HPV with the various methods used in this study were: HPV16 E6/E7 PCR: 0%; GP5+/6+ PCR: 4.5%; CDKN2A/p16 immunohistochemistry: 6.8%; in-situ hybridization for low and high risk HPV types: 52.3%; HPV6/11 L1 PCR: 72.7% and HPV6/11 E6 PCR: 79.5%. Disease progression showed no apparent dependence of the detected HPV type or clinical variables like age at diagnosis, sex, or additional drug application (Cidofovir and Bevacizumab). In conclusion, the broad-spectrum PCRs alone or in combination with immunohistochemistry of CDKN2A/p16 and in-situ hybridization are unsuitable for HPV detection in RLP. Based on the findings presented in this study the type specific PCRs targeting the E6 open reading frame are clearly superior in detection of HPV in this tumor entity. J. Med. Virol. 87:860-870, 2015. (c) 2015 Wiley Periodicals, Inc.

Background: The pathomechanism and location of idiopathic sudden sensorineural hearing loss (ISSHL) is unclear. In a previous case-control study, we found elevated fibrinogen concentrations and a higher prevalence of T allele carriers of the glycoprotein (Gp) Ia C807T polymorphism in ISSHL patients.Methodology: 127 patients with ISSHL (mean age 53.3 years, 48.8% females), who underwent a standard therapy with high dose steroids, pentoxifyllin and sterofundine over 8 days were included. We examined the influence of GpIa genotype and fibrinogen (BclI-, A312-, HaeIII-) genotype and fibrinogen plasma levels on hearing recovery after 8 weeks (change from baseline: 0 dB = no recovery, >0 to 10 dB = moderate recovery, >10 dB = good recovery). In a subsample of 59 patients with ISSHL, we further studied the association of platelet glycoprotein GpIa, Ib and IIIa densities on hearing recovery as well as the possible effect-modification of platelet glycoproteins on hearing recovery by plasma fibrinogen.Results: In univariate analysis, neither the GpIa genotype nor fibrinogen genotype (all p > 0.1) but lower fibrinogen levels (p = 0.029), less vertigo (p = 0.002) and lower GpIIIa receptor density (p > 0.037, n = 59) were associated with hearing recovery. In multivariate analysis, fibrinogen significantly modified the effect of GPIa receptor density on good hearing recovery (effect-modification on multiplicative scale OR = 0.45 (95% confidence interval (0.21-0.94)), p = 0.03). GPIb receptor density below the mean was associated with a 2-fold increase in good hearing recovery both in patients with fibrinogen levels above (p = 0.04) as well as in patients with fibrinogen levels below the mean (p = 0.06). There was no indication for an effect-modification (p = 0.97).Conclusions: The findings suggest a vascular/rheological origin of ISSHL with unique features of thrombosis in the inner ear artery that may include complex interrelationships among platelet glycoproteins and plasma fibrinogen.

Epigenetic alterations of the transcription factor 21 (TCF21) gene have been associated with head and neck squamous cell carcinoma (HNSCC) and other tumor entities. So far, however, no reports have appeared in the literature on TCF21 protein expression in HNSCC and its relevance as a putative biomarker.

Chronic rhinosinusitis with nasal polyps is a disease of high socio-economic importance. Despite intensive medical therapy and repetitive surgery recovery is often unsatisfactory. In the last few years there is increasing evidence that Staphylococcus aureus is a major disease-modifying agent of this and other respiratory diseases. Staphylococcus aureus leads to a shift in the local immune reaction by the production of enterotoxins. These enterotoxins could reinforce the eosinophilic inflammation in different ways; amplification of the release of Th2 cytokines and IgE formation, and downregulation of T-regulatory cytokines may all contribute to the severe and chronic inflammatory process. A deeper understanding of the inflammation process taking place in Staphylococcus aureus triggered chronic rhinosinusitis with nasal polyps is essential for the development of novel therapeutic approaches, such as anti-IL-5, anti-IgE and long-term antibiotic treatment.

Die chronische Rhinosinusitis mit Ausbildung von Nasenpolypen ist eine Erkrankung mit hoher sozioökonomischer Bedeutung. Die bisher verfügbaren Therapieverfahren führen in der Mehrheit der Fälle nicht zu einer dauerhaften Symptomfreiheit oder Heilung des Patienten. In den letzten Jahren gewinnt Staphylococcus aureus als ein die chronische Entzündung modifizierendes Agens bei der Rhinosinusitis, aber auch bei Erkrankungen der tieferen Atemwege zunehmend an Bedeutung. In der nasalen Mukosa führen Enterotoxine von Staphylococcus aureus zu einer Verstärkung der eosinophilen Inflammation über die Induktion von TH2-Zell-Zytokinen, die Ausbildung einer polyklonalen IgE-Antwort und die Herabregulation regulatorischer T-Zellen. Die zunehmenden Erkenntnisse über die pathophysiologischen Vorgänge bei einer durch Staphylococcus aureus getriggerten chronischen Rhinosinusitis eröffnen die Möglichkeit für neue Therapieoptionen über die Gabe von lokalen und systemischen Kortikoiden hinaus bis hin zur Langzeitantibiose, Anti-IL-5 und Anti-IgE-Therapie.

Background: Promoter methylation of the tumor suppressor gene Cyclin A1 could be associated with Human Papillomavirus 16 (HPV16) induced Head and Neck Squamous Cell Carcinoma (HNSCC) and Cervical Carcinoma. There is disagreement about the impact of this epigenetic event on protein expression of Cyclin A1 in malignant and non-malignant tissue and there hardly exists any information about possible relationships between Cyclin A1 expression and clinicopathological characteristics in HNSCC.Methods: We analyzed protein expression of Cyclin A1 in 81 HNSCC and 74 benign tonsils by immunohistochemistry and correlated it to Cyclin A1 methylation status, presence of HPV16 infection and other clinicopathological characteristics.Results: Overexpression of Cyclin A1 was more present in HNSCC than in tonsils (p < 0.001). In both entities, HNSCC and benign tonsils, expression of Cyclin A1 significantly correlated with the expression of Cyclin-dependent kinase-inhibitor p16 (p = 0.000672 and 0.00495). In tonsils, expression of Cyclin A1 was inversely proportional to age (p = 0.00000396), and further correlated with expression of tumor suppressor gene p53 (p = 0.000228). In HNSCC Cyclin A1 expression was associated with the presence of HPV16 DNA (p = 0.0014) and a lower recurrence rate in univariate and multivariate analysis (p = 0.002 and 0.013). Neither in HNSCC nor in tonsils Cyclin A1 expression correlated with promoter methylation.Conclusions: Cyclin A1 is an important cell cycle regulator with age-related increased expression in tonsils of children. HPV16 induces overexpression of Cyclin A1 in HNSCC despite promoter methylation. Overexpression of Cyclin A1 predicts a lower recurrence rate in HNSCC independently of HPV16.

Aberrant promoter methylation of specific genes and infection with human papillomavirus 16 (HPV16) are known risk factors for the development of Head and Neck Squamous Cell Carcinoma (HNSCC). Little knowledge exists on the interaction of HPV16 infection and promoter methylation in HNSCC. The promoter methylation status of 12 genes (TIMP3, CDH1, CDKN2A, DAPK1, transcription factor 21 (TCF21), CD44, MLH1, MGMT, RASSF1, cyclin A1 (CCNA1), LARS2, and CEBPA) was evaluated by methylation-specific polymerase chain reaction in 55 primary HNSCC and 31 controls. The results were correlated with HPV16 status and clinicopathological characteristics. CCNA1 and p53 protein expression were additionally determined by immunohistochemistry and compared with p53 mutation status. Methylation of DAPK1 (P = 0.043), CCNA1 (P = 0.016) and TCF21 (P = 0.0005) was significantly more present in HNSCC than in controls. The genes TIMP3 (P = 0.018) and CCNA1 (P = 0.015) showed higher methylation frequency in HPV16 positive HNSCC compared to HPV16 negative tumors. CCNA1 methylation did not correlate with CCNA1 protein expression and p53 mutation, respectively. Methylation of TCF21 was associated with higher age (P = 0.044) and nicotine abuse (P = 0.035). Methylation of CCNA1 was significantly more present in females (P = 0.003). Methylation of TCF21 and CCNA1 are important risk factors for HNSCC development. CCNA1 methylation may play a crucial role in HPV16-induced carcinogenesis of HNSCC independently of p53. (C) 2011 Wiley-Liss, Inc.

Background. Human papillomavirus (HPV) is a basic risk factor for head and neck squamous cell carcinoma (HNSCC). Little knowledge exists about the impact of HPV on clinical diagnostic and therapy of patients with HNSCC.Methods. We evaluated the evidence of HPV16 in 131 retrospectively collected HNSCC and associated cervical lymph node metastases by HPV16 real-time polymerase chain reaction (PCR) and p16 immunohistochemistry and its impact on clinicopathological characteristics.Results. HPV16-DNA and p16 overexpression were present in 27% of HNSCCs. All cervical lymph node metastases of HPV16-positive HNSCC showed HPV16-DNA. HPV16 was strongly associated with tumors arising from the oropharyngeal site (p < .000001), favorable outcome after standard therapy in univariate (p = .001) and multivariate (p = .0004) analysis, and cervical lymph node metastases before primary detection.Conclusion. HPV16-diagnostic in cervical lymph node metastases can predict the site of tumor origin in case of carcinoma of unknown primary (CUP) and favorable outcome and should, therefore, be included in routine diagnostic workup. (C) 2010 Wiley Periodicals, Inc. Head Neck 33: 856-862, 2011