Thomas Kühnel

EGFR, HER2, survivin, and loss of pSTAT3 characterize high-grade malignancy in salivary gland cancer with impact on prognosis

Increased gene copy number (high polysomy or amplification) of EGFR and HER2 has evolved as a predictor for response to targeted therapy. STAT3 and the apoptosis inhibitor survivin represent distinct oncogenes in various human neoplasms. The purpose of this study was to evaluate protein and gene status of these biomarkers by immunohistochemistry and dual color fluorescence in situ hybridization on tissue microarrays of 286 salivary gland carcinomas in the context of clinical and histopathologic characteristics. Diverse tumor types showed overexpression and increased gene copy number of EGFR and HER2. Amplification of HER2 was found in 35.5% of salivary duct carcinomas. Protein overexpression was strongly associated with high gene copy number for both EGFR and HER2 (P < .001). Overexpression and increased gene copy number of EGFR and HER2 were correlated to high-grade malignancy (P < .001) and unfavorable prognosis (P < .001). Strong nuclear staining of survivin was found in 18.9% of tumors and was associated with high-grade malignancy (P < .001), overexpression, and high gene copy number of EGFR and HER2 (P ≤ .05) as well as unfavorable prognosis (P < .001). Overexpression of nuclear pSTAT3 was found in 28.3% of tumors and correlated with well tumor differentiation (P < .001) and favorable prognosis (P = .001). Loss or weak expression of pSTAT3 was inversely associated with overexpression of survivin (P < .001) as well as overexpression and high gene copy number of EGFR and HER2 (P < .05). Overall, overexpression and increased gene copy number of EGFR and HER2 characterize high-grade malignancy with unfavorable prognosis in salivary gland cancer. Nuclear survivin typifies aggressive tumors with worse prognosis, whereas nuclear pSTAT3 might play a role as a tumor suppressor in absence of EGFR, HER2, and survivin.

Propofol versus sevoflurane: Bleeding in endoscopic sinus surgery

OBJECTIVE: Reduction of intraoperative bleeding is desirable to improve intraoperative visibility and to avoid complications. STUDY DESIGN: Prospective, controlled, randomized, double-blinded study. SETTING: Inclusion criteria were chronic rhinosinusitis with nasal polyps that involved all paranasal sinuses, Lund-CT score ≤ 12, and double-blind preoperative randomization of narcotics. Exclusion criteria included abnormal coagulation, perioperative blood pressure outside the range of 70 to 140 mmHg systolic and 50 to 90 mmHg diastolic and perioperative medication. Total blood loss (mL), blood loss per minute (mL/min), platelet function, and parameter for endoscopic vision were evaluated. RESULTS: Forty-six patients (22 sedated with sevoflurane/fentanyl, 24 sedated with propofol/fentanyl) completed the study. Total blood loss (300.1 ± 168.5 mL/276.9 ± 201.3 mL), blood loss per minute, and endoscopic vision showed no group difference. Platelet function was significantly impaired 45 minutes after onset of surgery in both groups, but more pronounced after propofol anesthesia. CONCLUSION: Under conditions of balanced circulatory parameter, equal blood loss and endoscopic vision can be achieved with both tested anesthetic regimens. During extended operations demonstrated thrombocyte impairment by propofol may become clinically relevant.

Frequency analysis of snoring sounds during simulated and nocturnal snoring

Despite several ways of investigation, such as clinical examination, drug-induced sleep endoscopy and pressure measurement of the upper airway, it is still difficult to locate the site of snoring exactly. Frequency analysis of snoring sounds is described as a promising diagnostic tool. The aim of the study was to examine simulated snoring under conditions awake, record the produced snoring sounds and compare those sounds with nocturnal snoring. A total of 50 snoring male patients were examined clinically by flexible nasal endoscopy and simulated snoring under conditions awake, and the simulated snoring sounds were recorded. Additionally, nocturnal snoring sounds were recorded during nighttime polysomnography. Snoring events were analyzed by fast-fourier-transformation and the intensity peaks 1–5 were evaluated. Rhythmic and non-rhythmic snoring events were distinguished depending on present obstructive apneas. Clinical and polysomnographical data were correlated with the results of the frequency analysis of the snoring sounds. Simulated snoring sounds revealed a low frequency of 200 Hz in intensity peaks 1 and 2 with an increase up to 3,000 Hz in peaks 3–5. Similar frequency patterns were detected in rhythmic nocturnal snoring. Non-rhythmic snoring events revealed frequency patterns between 2,000 and 3,000 Hz in all five intensity peaks. Simulated snoring resembles rhythmic nocturnal snoring with low-frequency intensity peaks, whereas non-rhythmic snoring revealed high frequencies. The examination during simulated snoring and frequency analysis of snoring sounds might contribute in locating the pathogenesis of snoring.

Morphological changes of the posterior airway space after tongue base suspension.

Objectives/Hypothesis: The objectives were 1) to demonstrate the efficacy of tongue base suspension with the Repose System in modifying the posterior airway space on the basis of morphological changes in the retrolingual space and 2) to determine the implications of this procedure for the treatment of obstructive sleep apnea syndrome on polysomnographic and psychometric data.

Clinical strategy in hereditary hemorrhagic telangiectasia.

Background Hereditary hemorrhagic telangiectasia (HHT) is a recurrent bleeding tendency caused by vascular malformations and preferentially involving the mucous membrane of the nose. The rhinological management of epistaxis is a challenge in which the frequency of bleeding has to be reduced without damage to the nasal mucosa, despite the fact that therapy necessarily has to be repeated. Methods The clinical course in 30 patients with HHT was monitored prospectively. Nasal mucosal efflorescences underwent Nd:YAG laser therapy at individually defined intervals, and the effect on the frequency and duration of bleeding was documented, as were adverse effects. Results No serious adverse effects (e.g., septal defects or synechiae) were observed as a consequence of therapy. During the course of laser therapy and ongoing compliance with nasal mucosal care instructions, the frequency of bleeding fell from “several times daily” to “every 2 weeks.” Conclusion In conjunction with Nd:YAG laser therapy, ongoing and consistent care of the nasal mucosa is a proven and effective treatment regimen in HHT. As an integral element in an interdisciplinary strategy for diagnosis and therapy, this regimen yields satisfactory quality of life while avoiding local complications.

The Upper Airway in Sleep-Disordered Breathing : A Clinical Prediction Model

An examination of the upper airway in patients with suspected sleep disordered breathing (SDB) is recommended prior to nighttime polysomnography (PSG) despite a reported low predictive value of those examinations. The aim of this study was to evaluate the data of the clinical examination and to create a clinical prediction model.

Triple test as predictive screen for unilateral weakness on caloric testing in routine practice.

Objective To investigate in vertigo patients in routine practice to what extent a rapid and straightforward triple bedside test (spontaneous nystagmus, head-shaking nystagmus, and the head impulse test) can predict a normal result on caloric testing. Study Design Prospective, single-blind, diagnostic study. Setting Tertiary referral center. Patients 151 patients (78 male and 73 female subjects; mean age, 52.5 ± 16.4 yr) presenting with acute or recent symptoms of vertigo. Intervention Diagnostic evaluation. Main Outcome Measure The negative predictive value (NPV) of the triple test in relation to a normal caloric test response. Results In unilateral weakness (UW) on caloric testing (UW, ≥25%), the triple test had sensitivity of 63.6%, specificity of 85.4%, a positive predictive value (PPV) of 71.4%, and an NPV of 80.4%. In other words, 80.4% of patients with a negative triple test also had a normal response on caloric testing. In pronounced canal paresis (UW, ≥50%), the triple test had sensitivity of 81.8%, specificity of 81.4%, a PPV of 55.1%, and an NPV of 94.1%. Significant differences were found between 2 subgroups assessed by examiners with differing levels of experience (p < 0.05). Conclusion The triple test represents a good screening tool that quickly and reliably excludes unilateral weakness and in particular pronounced canal paresis on caloric testing.

The impact of the microphone position on the frequency analysis of snoring sounds

Frequency analysis of snoring sounds has been reported as a diagnostic tool to differentiate between different sources of snoring. Several studies have been published presenting diverging results of the frequency analyses of snoring sounds. Depending on the position of the used microphones, the results of the frequency analysis of snoring sounds vary. The present study investigated the influence of different microphone positions on the outcome of the frequency analysis of snoring sounds. Nocturnal snoring was recorded simultaneously at six positions (air-coupled: 30 cm middle, 100 cm middle, 30 cm lateral to both sides of the patients’ head; body contact: neck and parasternal) in five patients. The used microphones had a flat frequency response and a similar frequency range (10/40 Hz–18 kHz). Frequency analysis was performed by fast Fourier transformation and frequency bands as well as peak intensities (Peaks 1–5) were detected. Air-coupled microphones presented a wider frequency range (60 Hz–10 kHz) compared to contact microphones. The contact microphone at cervical position presented a cut off at frequencies above 300 Hz, whereas the contact microphone at parasternal position revealed a cut off above 100 Hz. On an exemplary base, the study demonstrates that frequencies above 1,000 Hz do appear in complex snoring patterns, and it is emphasised that high frequencies are imported for the interpretation of snoring sounds with respect to the identification of the source of snoring. Contact microphones might be used in screening devices, but for a natural analysis of snoring sounds the use of air-coupled microphones is indispensable.

Diagnosis and treatment of snoring in adults–S2k Guideline of the German Society of Otorhinolaryngology, Head and Neck Surgery

Snoring is an obscure phenomenon, and many authors have tried to highlight the numerous facets in the past. Remarkable knowledge has been elaborated about obstructive snoring but not about primary snoring with its many epithets such as harmless, simple, habitual, benign, non-apnoeic, continuous, rhythmic etc. In 2010, the German Society of Otorhinolaryngology, Head and Neck Surgery published the S1 guideline: Diagnosis and Treatment of Snoring in Adults in ‘Sleep and Breathing’ 14: 317–321. The guideline has been revised and updated by the group of 10 German authors under the leadership of Boris Stuck in the present S2k guideline. It was initially published in the German journal ‘HNO’ 2013; 61: 944–57. The review of the literature was performed in June 2012 usingMedLine with the following search criteria: {‘snoring’ NOT ‘apnea’ NOT ‘apnoea’}, limited to the terms ‘English’, ‘German’, ‘adults’ and ‘humans’. I think it is very worthy of merit that the author group continued to follow the new developments of the difficult to explain phenomenon of snoring which is not a disease with a medical hazard. The authors wisely interpreted snoring in the sense of this guideline as a diagnosis of exclusion. To date, there is no satisfactory definition of snoring available and no validated questionnaire that aims to differentiate the snoring addressed by this guideline from snoring associated with obstructive sleep apnea. The numerous aspects of snoring are described in detail as to definition, nosology, aetiology, pathophysiology, epidemiology, health effects, clinical presentation, diagnostic measures (very widely discussed), therapeutic principles (conservative approaches—surgical treatments), and inclusive recommendations if possible. As studies about objectively assessing snoring and wellcontrolled clinical trials concerning the treatments and their outcome are lacking, it is not surprising that the words ‘may be’ and ‘could be’ are often to be found in the statements and recommendations. The guideline ends with a list of 93 references and a report of how this guideline was created. The process of compiling it is meticulously described including how all the German Societies were addressed which are engaged in sleep medicine. A detailed description of the commercial interests of the author group completes the guideline. This guideline has not only clarified the understanding of primary snoring but also left open questions. Snoring reminds me of the Lernean Hydra, the fearsome dragon-like monster with nine serpents’ heads. Hercules undertook to slay the beast by clubbing it on its multiple heads. But as soon as one head was crushed, two new ones sprang up in its place. Help came by his faithful companion Iolaus who burnt the wound of the cutoff heads. Thus, Hercules and Iolaus step by step overcame the monster. For the moment, there is no Hercules amongst us and only many companions like Iolaus who may perhaps be able to tame the monster ‘snoring’ in the long run.

Trauma of the midface

Fractures of the midface pose a serious medical problem as for their complexity, frequency and their socio-economic impact. Interdisciplinary approaches and up-to-date diagnostic and surgical techniques provide favorable results in the majority of cases though. Traffic accidents are the leading cause and male adults in their thirties are affected most often. Treatment algorithms for nasal bone fractures, maxillary and zygomatic fractures are widely agreed upon whereas trauma to the frontal sinus and the orbital apex are matter of current debate. Advances in endoscopic surgery and limitations of evidence based gain of knowledge are matters that are focused on in the corresponding chapter. As for the fractures of the frontal sinus a strong tendency towards minimized approaches can be seen. Obliteration and cranialization seem to decrease in numbers. Some critical remarks in terms of high dose methylprednisolone therapy for traumatic optic nerve injury seem to be appropriate. Intraoperative cone beam radiographs and preshaped titanium mesh implants for orbital reconstruction are new techniques and essential aspects in midface traumatology. Fractures of the anterior skull base with cerebrospinal fluid leaks show very promising results in endonasal endoscopic repair.