History of otorhinolaryngology in Germany before 1921.

In 2021, the German Society of Otorhinolaryngology, Head and Neck Surgery is celebrating the 100th anniversary of its foundation. The aim of this article is to present the main inventions and progress made in Germany before 1921, the date the society was founded. Three chronological periods are discernible: the history of otorhinolaryngology (ORL) in Germany until the beginning of the 19th century, focusing mainly on the development of scattered knowledge; the birth of the sub-specialties otology, laryngology (pharyngo-laryngology and endoscopy), and rhinology in the 19th century, combining advances in knowledge and implementation of academic structures; and the creation of the ORL specialty at the turn of the 20th century, mainly concentrating on academic organization and expansion. This period was crucial and allowed for the foundation of the German Society of Otorhinolaryngology, Head and Neck Surgery on solid ground. Germany played an important role in the development and progress of ORL internationally in the 19th century with such great contributors as Anton von Tröltsch, Hermann Schwartze, Otto Körner, Rudolf Voltolini, and Gustav Killian to mention a few.

In vitro and in vivo studies on blends of isotactic and atactic poly (3-hydroxybutyrate) for development of a dura substitute material.

Blends of semicrystalline isotactic poly(3-hydroxybutyrate) (PHB) with amorphous atactic PHB (at-PHB) were prepared by solution-casting using 30%, 50% and 70% at-PHB, and were studied for medical applications. The mechanical properties of the blends including the elastic modulus and elongation at break are strongly affected by the blend composition. The elastic modulus decreases with increasing fraction of at-PHB in the blend from 3350 MPa in the case of PHB to 170 MPa of PHB/at-PHB (30/70). In contrast, the elongation at break increases from 2% in pure PHB up to 50% in the case of the blend with 70% at-PHB. The in vitro degradation is changed as well. The molecular weight of PHB/at-PHB (30/70) is reduced to 5% after 2 years storage in phosphate buffer compared to 35% for pure PHB stored at identical conditions. The in vitro cell vitality is slightly reduced depending on the composition. PHB/at-PHB blends with 30% and 50% at-PHB were selected as dura substitute in minipigs based on the results of the in vitro investigation and the mechanical testing. Patch films with a structured surface on one side were fabricated by a dipping-leaching method. Dura defects were clinically and histologically examined 3, 6, and 9 months after implantation, confirming defect closure, prevention of adhesions to brain tissue, and no signs of inflammation or malignant degeneration. The PHB-based patch materials fulfill the requirements which are necessary for a dura substitute.

Laser scanning microscopy of the human larynx mucosa: a preliminary, ex vivo study.

OBJECTIVE: Laser scanning microscopy (LSM) supplies in vivo information from epithelia up to depths between 0.1 to 0.5 mm. The aim of this ex vivo prospective pilot study was to investigate the potential use of LSM for the diagnosis of laryngeal cancer and its precursors. METHODS: Forty-three larynx specimens of 26 patients (age 35-61 years, mean age 51.9+/-9.5 years; 7 women and 19 men) with laryngeal lesions were investigated with LSM. The LSM findings were compared with histopathologic sections. The following criteria were used for characterization of cancerous lesions: enlarged nuclei, enlarged cells with variable shapes, cluster of cells, increased nucleus/cytoplasm ratio, irregular cell architecture, and loss of cellular junctions characterized by lack of visualization of the cell membrane. RESULTS: LSM enables the visualization of epithelium up to the basement membrane, Reincke space, the subepithelial vessels, and the fibers of the subepithelial space. In contrast to the squamous epithelium, the respiratory epithelium bears kinocilia. The beat of the cilia and the directed mucous transport can be observed ex vivo. With the use of the presented malignancy criteria, a sensitivity of 72.7% and a specificity of 82.9% for differentiation of dysplasia and benign laryngeal lesions from cancer were reached. CONCLUSIONS: LSM in an ex vivo manner supplies microscopic images up to the subepithelial space. LSM could represent a new technology in laryngology to visualize larynx epithelia. In the next step, in vivo LSM will be applied to evaluate laryngeal lesion in vivo.

Subjective voice quality, communicative ability and swallowing after definitive radio(chemo)therapy, laryngectomy plus radio(chemo)therapy, or organ conservation surgery plus radio(chemo)therapy for laryngeal and hypopharyngeal cancer.

This retrospective analysis focusses on the impact of therapy on perceived long-term post-cancer treatment function. A validated questionnaire including items and components for the assessment of communicative ability, quality of voice and swallowing was sent to 129 patients. All patients were treated between 1998 and 2007. A total of 76 patients (58.9%) with carcinoma of the larynx or hypopharynx replied to the questionnaire. Data was evaluated retrospectively. Therapy delivered was definitive radio(chemo)therapy (defchRT/RT) (21/76, 28%), laryngectomy + radio(chemo)therapy (LE + chRT/RT) (28/76, 37%), or larynx conservation surgery + radio(chemo)therapy (LCS + chRT/RT) (27/76, 36%). Radiotherapy was administered using 2D- or 3D-conformal planning. The most common concomitant chemotherapy delivered was cisplatin + 5FU. For statistical analyses of the components, averages were calculated and tested using the Kruskal-Wallis test and the U-test of Mann and Whitney. Differences were assessed by the Monte Carlo method or Fisher's exact test. The single item rates were compared with Fisher's exact test. Mean follow-up was 56.7 months (range, 8-130 months). After defchRT/RT, patients trended towards more substantial-strong hoarseness compared with LCS + chRT/RT (P = 0.2). After LE, patients were dissatisfied with their artificial larynx/electrolarynx and the tone of their voice (P = 0.3, P = 0.07) and communicative ability (P = 0.005, P = 0.008) compared with those treated with defchRT/RT and LCS + chRT/RT, respectively. Dysphagia and additional percutaneous endoscopic gastrostomy (PEG) feeding were more frequent after defchRT/RT in comparison with the other two groups (P < 0.05). Voice quality and communicative ability were slightly worse after defchRT/RT and LE + chRT/RT, but satisfying with all treatment modalities. Further development of the therapy approach is necessary to reduce long-term side effects, with measures of post-treatment function as important endpoints.

Gene expression profiling of circulating natural killer cells in head and neck squamous cell carcinoma.

BACKGROUND: Natural killer (NK) cells are a major player of the innate immune system. Besides known risk factors for head and neck squamous cell carcinoma (HNSCC), impaired immune surveillance may as well lead to tumor manifestation. MATERIALS AND METHODS: In the present study, microarrays technologies were employed in order to perform gene expression profiling of NK cells in HNSCC patients. Differentially expressed genes have been detected in a comparative setting consisting of non-treated HNSCC patients, treated recurrence-free HNSCC patients and healthy control subjects. RESULTS: Cytokine receptors such as CCR7, IL-7R, and CXCR3 were down-regulated in non-treated HNSCC patients compared to healthy subjects, indicating impaired immune surveillance. In treated patients, up-regulated genes such as receptors for Fc fragments of specific antibodies, or ficolin-1 can be withheld as an immunological response to tumor manifestation. CONCLUSION: This study provides insights into gene expression changes in NK cells of HNSCC dependent upon clinical status and introduces several candidate genes suitable for further investigation.

Distribution of circulating natural killer cells and T lymphocytes in head and neck squamous cell carcinoma.

OBJECTIVE: Natural killer (NK) cells are capable of eliminating malignantly transformed cells without prior sensitization. In contrast to NK-cells, T lymphocytes possess antitumourous activity that is restricted to major histocompatibility complex (MHC) recognition. The aim of this study was to determine the causes of the different distributions of these cell types in the peripheral blood of patients with head and neck squamous cell carcinomas (HNSCC). METHODS: A cohort of 105 subjects was divided into three clinical groups: non-treated HNSCC patients, treated relapse-free HNSCC patients and healthy control subjects. Peripheral blood mononuclear cells (PBMC) were isolated from venous blood, subsets were depleted, flow cytometric counts were made and subsequently correlation analyses with clinical parameters were performed. RESULTS: Treated relapse-free HNSCC patients have a significantly increased mean proportion of NK-cells in PBMC of 26.39% (p<0.001), whereas T lymphocytes and natural killer-T-(NKT) cells of treated patients have a significantly decreased mean proportion in PBMC of 55.15% (p<0.05) at least 12 months after treatment. This inverse redistribution of these two subsets is reflected in a significantly increased mean NK/T-ratio of 0.54 (p<0.05) in treated patients. The NK/T-ratio correlates with the systemic invasiveness of the type of therapy patients undergo and is highest after surgery with adjuvant radiochemotherapy (0.64, rs=0.334, p<0.01). This appears to be a post-therapeutic long-term effect in treated patients, as they had a mean relapse-free period until venous puncture of 47.9 months in our study. We also demonstrated age-dependent changes in the peripheral distribution of T- and NK-cells. CONCLUSION: These findings reveal new aspects in understanding tumour biology and interactions with the cellular immune system which provide novel starting points for further research.

Limited mouth opening after primary therapy of head and neck cancer.

OBJECTIVES: Patients after surgery and radiation/chemoradiation for treatment of head and neck cancer often suffer from oral complications. These problems may be caused by surgery and radiation. Patients complain, for example, of swallowing problems and limited mouth opening (trismus). METHODS: The maximal interincisal mouth opening (MIO) was measured in patients treated with surgery and radiation/chemoradiation for head and neck cancer at the Department of Otorhinolaryngology at the University of Rostock. These patients also completed a 20-item questionnaire concerning nutritional, sensual, and speech disorders and pain. RESULTS: One hundred one patients (16 female and 85 male) returned the questionnaire and were included in the study. About 50% of the patients had a limited mouth opening (<36 mm); patients with oropharyngeal cancer had a significant higher risk for trismus (p = .024) than patients with other head and neck cancers, especially compared to patients with laryngeal cancer (p = .013). The questionnaire showed that especially patients with oral cancer report about problems with opening the mouth (73%), eating (65%), drinking (73%), xerostomia (92%), speech disorders (68%), and voice (62%). Patients with laryngeal cancer only reported about problems with xerostomia (62%), speech (83%), and voice (90%), similar to patients with pharyngeal cancer. CONCLUSIONS: About half of the patients who underwent primary treatment for oral and oropharyngeal cancer developed trismus and reported about problems with opening the mouth, eating, drinking, dry mouth, voice, and speech. Trismus has a negative impact on quality of life and should be a focus in the postoperative management of patients with oral and oropharyngeal cancer, and, if diagnosed, special treatment should be initialized.

Tracheostomy cannulas and voice prosthesis.

Cannulas and voice prostheses are mechanical aids for patients who had to undergo tracheotomy or laryngectomy for different reasons. For better understanding of the function of those artificial devices, first the indications and particularities of the previous surgical intervention are described in the context of this review. Despite the established procedure of percutaneous dilatation tracheotomy e.g. in intensive care units, the application of epithelised tracheostomas has its own position, especially when airway obstruction is persistent (e.g. caused by traumata, inflammations, or tumors) and a longer artificial ventilation or special care of the patient are required. In order to keep the airways open after tracheotomy, tracheostomy cannulas of different materials with different functions are available. For each patient the most appropriate type of cannula must be found. Voice prostheses are meanwhile the device of choice for rapid and efficient voice rehabilitation after laryngectomy. Individual sizes and materials allow adaptation of the voice prostheses to the individual anatomical situation of the patients. The combined application of voice prostheses with HME (Head and Moisture Exchanger) allows a good vocal as well as pulmonary rehabilitation. Precondition for efficient voice prosthesis is the observation of certain surgical principles during laryngectomy. The duration of the prosthesis mainly depends on material properties and biofilms, mostly consisting of funguses and bacteries. The quality of voice with valve prosthesis is clearly superior to esophagus prosthesis or electro-laryngeal voice. Whenever possible, tracheostoma valves for free-hand speech should be applied. Physicians taking care of patients with speech prostheses after laryngectomy should know exactly what to do in case the device fails or gets lost.

Prospective controlled study of microbial colonization of the trachea in tracheotomized and laryngectomized patients with HME (heat and moisture exchanger).

CONCLUSION: The use of heat and moisture exchangers (HMEs) does not endanger tracheostomy patients in terms of additional exposure to pathogenic microorganisms. OBJECTIVE: Stoma filters in the form of HMEs cause a beneficial convection of respiratory air in tracheotomized and laryngectomized patients. We investigated whether or not this may lead to an altered microbial ecology in the non-physiologically colonized lower respiratory tract. MATERIALS AND METHODS: To test this hypothesis, material from the trachea of stoma patients was prospectively collected utilizing a standardized swab technique and subsequent aerobic quantitative culture assays of the suspended and serially diluted material. With this approach, we examined the microbial flora in 6 and 5 patients after laryngectomy/tracheostomy, respectively, without any protection, in 11 patients after laryngectomy with a bib, and in 8 laryngectomized patients with an HME. RESULTS: In all three groups, Staphylococcus aureus and Candida albicans were most frequently demonstrated. The microbial count of facultative pathogenic agents ranged between 3×10(2) colony forming units (cfu)/ml and 10(6) cfu/ml and was similar in the three groups. With respect to the absence of inflammatory symptoms in every patient, all isolates could be regarded as colonizers. Among the antibiotics tested with each isolate, cefuroxime proved to be the most effective against the facultative pathogenic bacteria.

Poly(3-hydroxybutyrate) (PHB) patches for covering anterior skull base defects - an animal study with minipigs.

CONCLUSION: We conclude that PHB patch material may fulfil the specific requirements that are necessary for a dural substitute, including defect closure, stability and biocompatibility. Our results support the assumed positive influence of PHB on bone regeneration. OBJECTIVES: Although many experimental and clinical studies have been performed to identify a suitable material to repair defects of the dura mater, no ideal dural substitute is currently available. PHB is a biodegradable and biocompatible polymer that might serve as dural substitute and osteosynthesis material in cranial bone defects. MATERIALS AND METHODS: Different standardized PHB patches were used in six minipigs for covering defined bone defects in the anterior skull base including a dura mater lesion as well as in the frontal sinus front wall. After a defined time of implantation of 3, 6, and 9 months PHB patches were explanted and examined for clinical findings, biodegradation, presence of microorganisms, histological findings, and electron microscopy. RESULTS: The examinations revealed an increasing closure of bone defect corresponding with time. The anterior skull base bone defect was completely closed after 9 months. The histological findings revealed a connective tissue and callus formation around the PHB patches with fibroblasts and foreign body/giant cell reaction growing through PHB membrane pores. There were no reactions or adhesions between brain and PHB or dura mater and PHB, respectively. Investigations of biodegradation and electron microscopy revealed a continuous breakdown of PHB in the course of time with variations due to different PHB structures. Microbiological investigations could not detect any florid intracranial infection.