Attila Ovari

Geographical and anatomical influences on human papillomavirus prevalence diversity in head and neck squamous cell carcinoma in Germany

The increased knowledge regarding HPV-infections in head and neck squamous cell carcinoma (HNSCC) has unexpectedly contributed to several uncertainties related to i) prevalence diversities depending on tumour site and geographical origin of the patients, ii) proportion of HPV-driven tumours among HPV-DNA-positive cases, and iii) identification of patients with HPV-attributed survival benefit. To investigate this heterogeneity, we analysed 307 HNSCC cases (tonsillar, n=135; non-tonsillar, n=172) from eight health care centers mostly from Northern Germany and determined HPV-DNA/mRNA and p16INK4A-status and combined results with the patient outcome. Overall HPV-DNA prevalence rate was 23.5% (72/307); attributed to: 43.7% (59/135) and 7.6% (13/172) tonsillar and non-tonsillar cases, respectively. Among these, 96.6% tonsillar and 38.5% non-tonsillar SCC were HPV-mRNA-positive. Although the study cohort was composed of patients from regions of rather close proximity, prevalence rates showed diversities of up to 40% in HNSCC subsite analysis with the lowest prevalence for tonsillar SCC in metropolitan areas (22.2%) vs. 50.9% in rural areas. Survival analysis identified p16INK4A alone as strongest predictor, followed by HPV-DNA-status alone or in combination with p16INK4A. This survival benefit was shown for tonsillar and non-tonsillar cases. Smoking significantly correlated with HPV-status, however, it does not influence survival when stratified for HPV. In conclusion, the data emphasize the urge for further data on HPV-infection in HNSCC to, e.g. clarify to what extent survival benefits of p16INK4A-positive patients are truly attributed to HPV-infections.

Hearing Impairment Affects Dementia Incidence. An Analysis Based on Longitudinal Health Claims Data in Germany.

Recent research has revealed an association between hearing impairment and dementia. The objective of this study is to determine the effect of hearing impairment on dementia incidence in a longitudinal study, and whether ear, nose, and throat (ENT) specialist care, care level, institutionalization, or depression mediates or moderates this pathway. The present study used a longitudinal sample of 154,783 persons aged 65 and older from claims data of the largest German health insurer; containing 14,602 incident dementia diagnoses between 2006 and 2010. Dementia and hearing impairment diagnoses were defined according to International Classification of Diseases, Tenth Revision, codes. We used a Kaplan Meier estimator and performed Cox proportional hazard models to explore the effect of hearing impairment on dementia incidence, controlling for ENT specialist care, care level, institutionalization, and depression. Gender, age, and comorbidities were controlled for as potential confounders. Patients with bilateral (HR = 1.43, p<0.001) and side-unspecified (HR = 1.20, p<0.001) hearing impairment had higher risks of dementia incidence than patients without hearing impairment. We found no significant effect for unilateral hearing impairment and other diseases of the ear. The effect of hearing impairment was only partly mediated through ENT specialist utilization. Significant interaction between hearing impairment and specialist care, care level, and institutionalization, respectively, indicated moderating effects. We discuss possible explanations for these effects. This study underlines the importance of the association between hearing impairment and dementia. Preserving hearing ability may maintain social participation and may reduce the burden associated with dementia. The particular impact of hearing aid use should be the subject of further investigations, as it offers potential intervention on the pathway to dementia.

Regional Pattern of Dementia and Prevalence of Hearing Impairment in Germany

To determine the association between hearing impairment and dementia.

The antileukoprotease secretory leukocyte protease inhibitor (SLPI) and its role in the prevention of HPV-infections in head and neck squamous cell carcinoma

Recently, we demonstrated a significant inverse correlation between HPV-infection and SLPI-expression suggesting that SLPI protects against HPV-infection of HNSCC. Here we analyzed in a single lab setting 307 formalin-fixed paraffin-embedded HNSCC cases (tonsillar n = 135; non-tonsillar: n = 172) from eight health care centers. Samples were analyzed for SLPI gene- and protein-expression. Annexin A2, its heterotetramer A2t, putatively facilitating HPV- and SLPI-cell entry, was measured to study the correlation between SLPI and annexin A2. Data were correlated with tobacco consumption and HPV-status. Overall, HPV-DNA prevalence was 23.5% (72/307); attributed to: 43.7% (59/135) tonsillar and 7.6% (13/172) non-tonsillar cases. Smoking resulted in 6.44-fold increased and HPV-infection in 3.46-fold decreased SLPI-gene expression in all HNSCC with similar significant results obtained in tonsillar and non-tonsillar SCC separately. Correlating annexin A2- and SLPI-gene expression showed a significant surplus of annexin A2 in HPV-positive tumors (4.21× more annexin A2) and 6.72× more annexin A2 than SLPI in nonsmokers in all HNSCCs and similar significant results for both tumor entities separately. The surplus of annexin A2 in non-smokers and HPV-positive patients supports our hypothesis that decreased SLPI levels facilitate HPV-infection i.e., increased SLPI-expression may protect against HPV-infection of tonsillar and non-tonsillar SCC.

Conservative management of post-intubation tracheal tears-report of three cases.

Iatrogenic tracheal rupture is a rare complication after intubation. We present three patients with tracheal tears. In all of these patients, a common finding was a lesion of the posterior tracheal wall with postoperative subcutaneous and emphysema as the first clinical sign of the rupture. Diagnosis and follow-up were based on clinical and endoscopic findings and chest computed tomography (CT) scans. In our cases with progressive subcutaneous and mediastinal emphysema or dyspnea, we performed a tracheotomy and bypassed the lesion with a tracheostomy tube to avoid an increase in air leakage into the mediastinum. Under broad-spectrum antibiotic therapy, no mediastinitis occurred and all patients survived without sequelae. Closure of tracheostomy was scheduled for 1-2 months after tracheal injury. Analysis of surgical and anesthesiological procedures revealed no abnormalities and the accumulation of tracheal injuries was considered as accidental. We found that in clinically stable patients with spontaneous breathing and with no mediastinitis, a conservative management of tracheal tears is a safe procedure.

Optical coherence tomography in otolaryngology

Optical coherence tomography is an imaging technique based on coherence interferometry. It is used in many medical fields due to its non-invasive imaging capabilities with micrometer resolution. The aim of the authors was to review the applicability of the optical coherence tomography in otolaryngology. Literature data and their own studies show that optical coherence tomography is a reliable method for identifying and targeted biopsy of inflammated, pre-malignant or cancer tissue in human laryngeal and pharyngeal mucosa. Another emerging field for optical coherence tomography is diagnosis of middle ear diseases, especially stapes ankylosis and cholesteatoma.

Can nasal decongestants improve eustachian tube function

Objective To evaluate the effect of nasal decongestants on eustachian tube (ET) opening. Study design A prospective nonrandomized study. Setting A tertiary referral center. Patients Twenty-four patients (44 ears) with intact eardrums, 39 patients (43 ears) having a noninfected eardrum defect, and six patients with an upper airway infection. Interventions Nasal or intratympanal (in perforated ears) application of a nasal decongestant (xylometazoline 0.1%). Main outcome measures Change of tube opening quality (yes or no; better or worse) measuring tube opening parameters (pressure, latency) using the Estève method and pressure equalization tests (swallowing at negative and positive external ear canal pressures). Results In most cases, nasal decongestion or intratympanal use of decongestants have no effect on ET opening. Improvement in tube opening is rather an exception and, in a minority of patients, a reduced ET function was evident. Conclusion Our acute studies revealed no improvement in eustachian ventilatory tube function with the administration of nasal decongestants.

CORRESPONDENCE: LETTERS: Fingertip support technique and instrument support for reducing unintentional instrument movements in otology

Sir, Physiological tremor is a main risk factor in microsurgery and the range of tremor magnitude varies widely. Our team developed two simple but very effective low-cost techniques for the reduction of physiological tremor. ‘Fingertip support’ technique (FS) is basically a mechanical support called ‘bridge’ for the first three (instrument holding) fingers of the surgeon. This bridge can be placed both above and near the operating site (Fig. 2). This technique eliminates interference from all of the joints trans-

Fingertip support technique and instrument support for reducing unintentional instrument movements in otology.

Sir, Physiological tremor is a main risk factor in microsurgery and the range of tremor magnitude varies widely. Our team developed two simple but very effective low-cost techniques for the reduction of physiological tremor. ‘Fingertip support’ technique (FS) is basically a mechanical support called ‘bridge’ for the first three (instrument holding) fingers of the surgeon. This bridge can be placed both above and near the operating site (Fig. 2). This technique eliminates interference from all of the joints trans-

Positioning Accuracy in Otosurgery Measured with Optical Tracking.

Objectives To assess positioning accuracy in otosurgery and to test the impact of the two-handed instrument holding technique and the instrument support technique on surgical precision. To test an otologic training model with optical tracking. Study Design In total, 14 ENT surgeons in the same department with different levels of surgical experience performed static and dynamic tasks with otologic microinstruments under simulated otosurgical conditions. Methods Tip motion of the microinstrument was registered in three dimensions by optical tracking during 10 different tasks simulating surgical steps such as prosthesis crimping and dissection of the middle ear using formalin-fixed temporal bone. Instrument marker trajectories were compared within groups of experienced and less experienced surgeons performing uncompensated or compensated exercises. Results Experienced surgeons have significantly better positioning accuracy than novice ear surgeons in terms of mean displacement values of marker trajectories. The instrument support and the two-handed instrument holding techniques significantly reduce surgeons’ tremor. The laboratory set-up presented in this study provides precise feedback for otosurgeons about their surgical skills and proved to be a useful device for otosurgical training. Conclusions Simple tremor compensation techniques may offer trainees the potential to improve their positioning accuracy to the level of more experienced surgeons. Training in an experimental otologic environment with optical tracking may aid acquisition of technical skills in middle ear surgery and potentially shorten the learning curve. Thus, simulated exercises of surgical steps should be integrated into the training of otosurgeons.