H. Steinhart

Upper Airway Collapsibility in Habitual Snorers and Sleep Apneics: Evaluation with Drug-induced Sleep Endoscopy

Increased upper airway collapsibility has been suspected of being involved in the pathogenesis of sleep-related diseases. It is assumed that patients with severe obstructive sleep apnea syndrome (OSAS) show a stronger collapse of the upper airway compared with habitual snorers. It was the objective of this study to analyze the patterns of upper airway collapse in habitual snorers and patients with OSAS and to correlate these results with data from polysomnography. Endoscopy was carried out during drug-induced sleep (with propofol) and collapsibility was analyzed at two major levels (palatal and tongue base). A total of 207 habitual snorers and 117 patients with OSAS underwent endoscopy after overnight polysomnography in our sleep laboratory. In 95% of cases we were able to induce snoring during drug-induced sleep. The collapsibility in the area of the base of the tongue correlated with higher values of the respiratory disturbance index (RDI) as recorded by standard polysomnography. Patients with OSAS showed significantly stronger collapsibility compared with snorers. The difference was more evident at the tongue-base level. We found no significant correlation between the applied CPAP pressure and collapsibility in patients with OSAS. These results show that collapsibility at the tongue-base level is a factor relevant in sleep-related breathing disorders.Increased upper airway collapsibility has been suspected of being involved in the pathogenesis of sleep-related diseases. It is assumed that patients with severe obstructive sleep apnea syndrome (OSAS) show a stronger collapse of the upper airway compared with habitual snorers. It was the objective of this study to analyze the patterns of upper airway collapse in habitual snorers and patients with OSAS and to correlate these results with data from polysomnography. Endoscopy was carried out during drug-induced sleep (with propofol) and collapsibility was analyzed at two major levels (palatal and tongue base). A total of 207 habitual snorers and 117 patients with OSAS underwent endoscopy after overnight polysomnography in our sleep laboratory. In 95% of cases we were able to induce snoring during drug-induced sleep. The collapsibility in the area of the base of the tongue correlated with higher values of the respiratory disturbance index (RDI) as recorded by standard polysomnography. Patients with OSAS showed significantly stronger collapsibility compared with snorers. The difference was more evident at the tongue-base level. We found no significant correlation between the applied CPAP pressure and collapsibility in patients with OSAS. These results show that collapsibility at the tongue-base level is a factor relevant in sleep-related breathing disorders.

Olfactory neuroblastoma: The University Of Erlangen–Nuremberg experience 1975-2000

OBJECTIVE: Olfactory neuroblastoma constitutes a rare and, in clinical terms, biologically variable tumor of the nasal cavity, paranasal sinuses, and the base of the skull and presents a challenge to a modern multidisciplinary therapy. Generally acknowledged prognostic factors and a standard therapy fail to exist. METHODS: Between 1975 and 2000 we diagnosed and treated 26 patients with an olfactory neuroblastoma. According to Kadishs classification, 1 patient (4%) showed stage A, 16 patients (53%) stage B, and 11 cases (43%) stage C. Hyams grading was established in 81% of all cases. Fifty-two percent were thus classified as low-grade and 48% as highgrade tumors. Surgical therapy was performed on 23 patients (88.5%), surgery being the exclusive form of therapy (monotherapy) in 5 of these patients. Combined therapy was carried out in 18 cases (surgery, radiotherapy, chemotherapy). RESULTS: Currently, 16 of 26 treated patients (61.5%) are alive. The disease-specific 10- and 15-year survival determined according to Kaplan-Meier is 76.2%. Fifteen-year survival amounts to 86.7% for smaller tumors (Kadish A/B) and 63.6% for advanced tumors (Kadish C). Seven (26.9%) of the overall group of treated patients developed a recurrence. Salvage therapy was successful in 60% (3 of 5 patients). Fifteen-year survival following salvage therapy amounts to 60%. Patients with highgrade tumors exhibit a significantly reduced 10-year survival (40%) compared to patients with low-grade tumors (100%). CONCLUSIONS: The therapy of olfactory neuroblastoma calls for an interdisciplinary multimodal therapeutic strategy, particularly in the case of advanced tumors. Tumor staging and histopathologic grading according to Hyams are important factors for survival and prognosis. Aggressive salvage therapy can lead to a distinct improvement of long-term survival. (Otolaryngol Head Neck Surg 2004; 130:567-74.)

Fine-structural investigations of the effect of nCPAP-mask application on the nasal mucosa.

The treatment success of nasal continuous positive airway pressure (nCPAP)-therapy is dependent, on the one hand, on the achieved relief of complaints and, on the other hand, on long-term patient compliance and avoidance of compliance-related complaints. Next to the problem of mask application, nasal complaints comprise the most frequently reported side-effects and are among the primary factors causing nCPAP-therapy to be discontinued prematurely. To assess the morphological changes in the nasal mucosa during nCPAP-therapy, we excised specimens of nasal mucosa tissue from 10 patients with obstructive sleep apnoea syndrome (OSAS) before and 3-10 months after establishing nCPAP-mask compliance. The specimens were examined by electron microscopy. In all these patients compliance with the CPAP-mask marked the initial part of therapy. In addition, mucociliary clearance was assessed by the saccharin test before and after therapy. In all patients the nasal epithelium underwent fundamental changes upon CPAP-therapy, which became manifest as modifications in the shape of epithelial cells, conglutination and clumping of the microvilli, and the appearance of immunocompetent cells. Once patients were nCPAP-mask compliant, mucociliary clearance was distinctly prolonged in all cases. A successful therapeutic concept should provide normalization of room temperature and air humidity once nCPAP-mask compliance has been achieved and include regular assessment of the condition of the mucosa in the upper respiratory tract. Only by these measures can nasal complications be countered or given therapy at an early stage.The treatment success of nasal continuous positive airway pressure (nCPAP)-therapy is dependent, on the one hand, on the achieved relief of complaints and, on the other hand, on long-term patient compliance and avoidance of compliance-related complaints. Next to the problem of mask application, nasal complaints comprise the most frequently reported side-effects and are among the primary factors causing nCPAP-therapy to be discontinued prematurely. To assess the morphological changes in the nasal mucosa during nCPAP-therapy, we excised specimens of nasal mucosa tissue from 10 patients with obstructive sleep apnoea syndrome (OSAS) before and 3-10 months after establishing nCPAP-mask compliance. The specimens were examined by electron microscopy. In all these patients compliance with the CPAP-mask marked the initial part of therapy. In addition, mucociliary clearance was assessed by the saccharin test before and after therapy. In all patients the nasal epithelium underwent fundamental changes upon CPAP-therapy, which became manifest as modifications in the shape of epithelial cells, conglutination and clumping of the microvilli, and the appearance of immunocompetent cells. Once patients were nCPAP-mask compliant, mucociliary clearance was distinctly prolonged in all cases. A successful therapeutic concept should provide normalization of room temperature and air humidity once nCPAP-mask compliance has been achieved and include regular assessment of the condition of the mucosa in the upper respiratory tract. Only by these measures can nasal complications be countered or given therapy at an early stage.

Evaluation of ozonated oxygen in an experimental animal model of osteomyelitis as a further treatment option for skull-base osteomyelitis.

Abstract The standard treatment of chronic skull-base osteomyelitis is antibiotics and surgical removal of sequestrums. Hyperbaric oxygen therapy has been found to be a useful method for managing refractory cases of chronic osteomyelitis. Since a minimal blood supply is needed for hyperbaric oxygen therapy, chronic osteomyelitis can produce necrotic infected areas that are not nutrified and therefore not assessible for hyperbaric oxygen therapy. Ozone is known to be an oxidizing medium with a strong bactericidal effect. We investigated the influence of locally applied ozonated oxygen on the development of chronic osteomyelitis in an experimental animal model using the femur of the rabbit. The proximal sides of the femurs of 40 rabbits were prepared and a needle inserted into the intramedullary cavity. Osteomyelitis was induced with an infusion of Staphyloccus aureus and sodium morrhuate into the bone. The needle was left in a intramedullar location. After a 4-week delay animals were randomly separated into treatment and control groups. The infected femur of treated animals was flushed three times a day with 20 ml of ozonated oxygen at an ozone concentration of 107 μg/ml O2 over periods of 2 or 4 weeks. Clinical, radiographic and microbiological findings were documented. Chronic osteomyelitis occurred in all animals. Ten rabbits were excluded from further study during the investigation because of excessive weight loss (>15% of the original weight). Bacterial cultures showed no significant reduction of S. aureus concentrations in the ozone-treated group, although comparison of radiographic results revealed less serious osteomyelitis-related bone damage in these animals (P < 0.01). These findings indicate that refractory osteomyelitis in the head and neck may benefit from locally applied “flush” therapy with ozonated oxygen in addtion to treatment with antibiotics, surgery and hyperbaric oxygen.

COMBINED SURGICAL LIPECTOMY AND LIPOSUCTION IN THE TREATMENT OF BENIGN SYMMETRICAL LIPOMATOSIS OF THE HEAD AND NECK

Benign symmetrical lipomatosis (Madelung syndrome) is a rare disease of unknown aetiology, which is characterised by diffuse growth of non-encapsulated lipomas. Between 1995 and 2000 we treated 11 patients with benign symmetrical lipomatosis in the head and neck. The group comprised 10 men and one woman aged 34 to 62 years (mean 47). The most common complaints were reduced range of movement of the head and obstruction when eating or speaking. Combined lipectomy and liposuction were done for all patients, with liposuction being done at a second session. The mean follow-up period was 2.7 years. The functional results were satisfactory in all patients. Nine of the 11 patients were also satisfied with the aesthetic outcome. Two patients developed recurrence 1.5 and 2 years after the operation, respectively. There were no serious complications. We think that combined lipectomy and liposuction is a successful procedure for treating benign symmetrical lipomatosis in the head and neck region. Nevertheless, the advantages and drawbacks of the two techniques should be considered preoperatively.

Surgical Application of a New Robotic System for Paranasal Sinus Surgery

The applicability of a robotic system for fully automated surgical procedures approaching the sphenoid sinus is evaluated. An integrated robotic system, A73, for computer navigation-guided, fully automated, and telemanipulation robotic performance is described. Details of the system comprising newly designed surgical instruments for robotic operations and preoperative planning protocols are provided. Experiments with an operational accuracy of less than 1 mm were followed by surgical tests, in which the results of fully automated and telemanipulation performances on 5 cadaveric heads are seen. The A73 system has been successfully used for a reproducible and accurate resection of the anterior wall of the sphenoid sinus. Therefore, we conclude that this system is suited for further testing toward approaching fully automated and more complex procedures of paranasal surgery.

Metastatic and inflammatory cervical lymph nodes as analyzed by contrast-enhanced color-coded Doppler ultrasonography: quantitative dynamic perfusion patterns and histopathologic correlation.

Use of contrast-enhanced color-coded Doppler (ultra)sonography (CCDS) in evaluating enlarged lymph nodes has been subject to numerous attempts to define criteria for differentiation between benign and malignant lesions. Evaluation of dynamic perfusion patterns with contrast-enhanced CCDS in cervical lymph nodes offers new possibilities of differential diagnosis. A total of 28 patients with clinically enlarged lymph nodes were included in this study. Contrast-enhanced CCDS was performed on each patient. The color signals from nodes <15 mm in diameter were analyzed with a specialized computer program. Each node was later examined through immunohistochemical staining. Vascularization as shown by unenhanced CCDS was significantly greater in metastatic lymph nodes than in reactively enlarged lymph nodes (8.66% versus 2.81%; p = .01). The maximum vascularization area after contrast injection did not show any significant change (26.61 % versus 28.63%; p = .75). Comparison of values obtained before and after contrast enhancement showed the largest relative increase in vascularization in inflammatory lymph nodes, from a factor of 19.55 to a factor of 10.03 (p = .025). Dynamic values such as contrast enhancement, behavior of dynamic values referred to time, and the evaluated vascularized area did not show any significant difference. The metastatic lymph nodes (5.46 versus 3.33; p = .007) predominantly consisted of large blood vessels. The increased vascularization in the unenhanced CCDS examination of metastatic lymph nodes seems to be associated with the increased number of large blood vessels. An increased vessel density, due to a greater number of total vessels, is related to an inflammatory process. Color Doppler mapping has been proven to depict useful aspects distinguishing benign from malignant lymph nodes of the neck; however, a definitive differentiation between lymph nodes involved with malignancy and inflammatory changes remains difficult.

Contrast-enhanced color Doppler sonography of parotid gland tumors.

Abstract.The objective of the present study is to assess the potential of color Doppler sonography in imaging tumors of the parotid gland enhanced by application of ultrasound contrast agents. To this end 26 patients with tumors of the parotid gland were investigated. The color Doppler signal areas before and after administration of Doppler signal-enhancing agent (Levovist, Schering, Germany) were determined by means of computer-assisted analysis, and the relevant parameters were evaluated. The tumors can be classified as follows: 11 pleomorphic adenomas, 8 adenolymphomas and two squamous cell carcinomas of the parotid gland, two lymph nodes, one adenoma, one neurinoma of the facial nerve and one non-Hodgkins lymphoma. Before the administration of Doppler signal-enhancing agent, the adenolymphomas showed a significantly stronger Doppler signal area as compared to the pleomorphic adenomas. The maximum color Doppler signal area after administration of Doppler signal-enhancing agent showed no difference within both groups. If one considers the relative change in the Doppler signal area before and after applying enhancing agent, however, a significantly stronger enhancement of perfusion (increase in Doppler signal area) is noted within pleomorphic adenomas. The changes in the Doppler signal area after administration of signal-enhancing agent show a different course depending on the histology of the investigated tumors.

Tumor-associated antigenic pattern in squamous cell carcinomas of the head and neck – Analysed by SEREX

Most immuno-therapeutic approaches are based on tumor-associated antigens and many newly identified proteins have led to trials exploiting their possible therapeutic applicability. So far only limited information on the antigenic profile of head and neck squamous cell carcinomas (HNSCC) exists. Serological analysis of tumor antigens by recombinant cDNA expression cloning (SEREX) was used to identify the immunogenic patterns in our HNSCC patient collective. A cDNA expression library derived from a pharynx HNSCC case was screened with autologous and heterologous sera. Thirty-seven positive clones coding for 17 immunoreactive gene products, which elicited an in vivo tumor response, were found. Results were confirmed and extended by expression analysis using RT-PCR and in situ-hybridisation. The protein-sequence of five clones exists so far only hypothetically. Of all identified proteins only KIAA0530 has previously been associated with a HNSCC related immune response. All other proteins have not yet been described in a context with HNSCC antigenic patterns. Antibodies against a heat shock transcription factor 2 (HSF2) were found in 2 out of 10 sera from HNSCC patients. In summary, using the SEREX technique, we isolated 17 immunogenic antigens in HNSCCs and confirmed the clinical relevance of KIAA0530. Further analysis concerning their feasibility as target structures for an immunotherapy approach is currently conducted.

Pharyngolaryngoskopische Befunde bei Patienten mit obstruktivem Schlafapnoesyndrom und primärem Schnarchen

ZusammenfassungHintergrund und Fragestellung. Die Vorhersage des Ortes der Obstruktion oder des Weichteilkollapses bei Patienten mit primärem Schnarchen und obstruktivem Schlafapnoesyndrom war in den letzten Jahren häufig Thema von Untersuchungen. Die flexible Nasopharyngolaryngoskopie im Schlaf oder in Sedierung ist in diesem Zusammenhang eine bekannte Untersuchungsmethode, trotz ihrer nichtphysiologischen Basis. Patienten/Methodik. Die Ergebnisse von 324 Patienten, die neben der Routinediagnostik im Schlaflabor mittels einer flexiblen Pharyngolaryngoskopie im Wachzustand und in Propofol-Sedierung untersucht wurden, werden beschrieben. Hierbei werden Vergleiche zum Müller-Manöver und zu den jeweiligen Polysomnographieergebnissen angestellt und die therapeutische Konsequenz dieser Zusatzdiagnostik diskutiert. Ergebnisse. In 95% der Fälle konnte während des medikamentös induzierten Schlafs Schnarchen registriert werden. Auf Höhe des Zungengrunds fand sich eine signifikant stärkere Kollapsneigung bei der Untersuchung im Propofol-Schlaf verglichen mit den Befunden des Müller-Manövers. Die Stärke des Zungengrundkollapses korrelierte mit dem in der Polysomnographie ermittelten RDI (respiratory disturbance index). Schlussfolgerungen. Insgesamt fand sich ein deutlicher Unterschied zwischen der Ausprägung des Weichteilkollapses beim Müller-Manöver und beim Propofol-Schlaf; Schnarchen und Kollapsneigung ließen sich zuverlässig beobachten. Die Pharyngolaryngoskopie erwies sich als einfach und sicher durchführbare, komplikationsarme und aussagekräftige Zusatzdiagnostik im Rahmen der Abklärung des primären Schnarchens und des obstruktivem Schlafapnoesyndrom.AbstractBackground and objective. The localization of an upper airway collapse in snorers and patients suffering from obstructive sleep apnea was a subject frequently discussed in the last few years. Pharyngolaryngoscopy during sleep or drug-induced sleep allows evaluation of upper airway conditions. Patients/methods. A total of 324 patients suffering from snoring or obstructive sleep apnea underwent flexible pharyngolaryngoscopy while awake and under propofol-induced sedation in the course of routine diagnostic procedures in the sleeping lab. In this study, the results of pharyngolaryngoscopy are compared to results of the Müller maneuver and polysomnographic recordings. The therapeutic consequences of this additional investigation are discussed. Results. In 95% of cases snoring was observed during drug-induced sleep. A significant discrepancy was seen between results of the endoscopy while being awake (Müller maneuver) and during drug-induced sleep. The degree of collapse differed significantly in the area of the base of the tongue. Severe collapse was seen much more often with pharyngoscopy during drug-induced sleep compared to the results during the Müller maneuver. Conclusions. The collapsibility in the area of the base of the tongue correlated with higher results in the RDI (respiratory disturbance index) registered with standard polysomnography. Snoring and upper airway collapse were easily surveyed, and the pharyngolaryngoscopy during propofol-induced sleep proved to be a simple, safe, readily controllable and effective supplementary diagnostic device for the diagnosis and treatment of obstructive sleep apnea and snoring.