[Current oncologic concepts and emerging techniques for imaging of head and neck squamous cell cancer]. / Aktuelle Standards und Fortschritte in der onkologischen Bildgebung von Kopf-Hals-Tumoren.

The incidence of head and neck squamous cell carcinoma (HNSCC) is increasing and currently they account for 5% of all malignancies worldwide. Inspite of ongoing developments in diagnostic imaging and new therapeutic facilities, HNSCC still represents a multidisciplinary challenge. One of the most important prognostic factors in HNSCC is the presence of lymph node metastases. Patients with confirmed nodal involvement have a considerable reduction of their 5-year overall survival rate. In the era of individually optimised surgery, chemotherapy and intensity modulated radiotherapy, the main role of pre- and posttherapeutic imaging remains cancer detection at an early stage and accurate follow-up. The combined effort of early diagnosis and close patient monitoring after surgery and/or radio-chemotherapy influences disease progression and outcome prediction in patients with HNSCC. This review article focuses on currrent oncologic concepts and emerging tools in imaging of head and neck squamous cell cancer. Besides the diagnostic spectrum of the individual imaging modalities, their limitations are also discussed. One main part of this article is dedicated to PET-CT which combines functional and morphological imaging. Furthermore latest developments in MRT are presented with regard to lymph node staging and response prediction. Last but not least, a clinical contribution in this review explains, which information the head and neck surgeon requires from the multimodality imaging and its impact on operation planning.

Ciliary function of the nose in patients with Osler`s disease and the effect of topically applied estrogens as a nose ointment.

BACKGROUND: In recent years, the positive effect of topically applied estriol nose ointment in the adjuvant therapy of Morbus-Rendu-Osler (HHT) has been proven. Due to the induced metaplasia, a complete destruction of the ciliated cells may be expected. However, data regarding the ciliary function of HHT patients with and without the use of topical estriol application are currently lacking. METHODOLOGY/PRINCIPAL: Ciliated samples were obtained by gently brushing the inferior nasal turbinate of 19 healthy volunteers and 15 patients with known HHT (8 of them regularly using 0.1% estriol nose ointment for 2 years (HHTwE) and 7 of them not using the ointment in the last 12 months (HHTwoE)). Analysis was done with an inverted phase contrast microscope connected to a high-speed digital camera. Recorded parameters were the visual integrity (VI) of the ciliary beat and its frequency (CBF) in Hz. RESULTS: The VI index of all samples showed an undisrupted, even beating pattern with a difference between the three groups. The mean CBF in all HHT patients was reduced compared to the control group`s mean CBF. Within the HHT group itself, the mean CBF was reduced in the HHTwE group compared to the HHTwoE group. CONCLUSIONS: The ciliary beat frequency of HHT patients is impaired compared to the control group and even more so if the HHT patients topically apply estriol more than 6 months. An undisrupted beating pattern is found in the HHTwE group despite the fact that estrogens induce a transformation of the ciliated columnar into a keratinizing squamous epithelium. This data may justify the adjuvant application of estriol as a nose ointment in the treatment of epistaxis in HHT patients without the fear of damage to the nose`s mucus clearance.

[Rhinophyma in rosacea. What does surgery achieve?]. / Rhinophym bei Rosazea. Was leistet die operative Therapie?

Rhinophyma is a benign dermatological disease of the nose which affects primarily Caucasian men in their fifth decade of life. Its main characteristic is a slowly progressive hyperplasia of the sebaceous glands and the adjacent tissue with irregular thickening of the nasal skin and nodular deformation. It is defined as the end stage of acne rosacea. The main reasons for patients to seek medical help are cosmetic problems and functional impairments such as nasal airway obstruction or even difficulty in eating. Surgery is indisputably the treatment of choice for rhinophyma. This article gives an overview on the clinical and histopathologic findings of rhinophyma as well as the different treatment options with their pros and cons as described in literature.

[Impact of TGF-beta1 antisense on collagen-binding integrins in keloid]. / TGF-beta1-Antisense beeinflusst kollagenbindende Integrine im Keloid.

BACKGROUND: The treatment of keloids remains challenging due to sparse knowledge about the pathogenesis of this disease. Transforming growth factor (TGF)-beta1 plays a central role in keloid formation. Cell-matrix communication is controlled by integrins, the expression of which can be regulated by TGF-beta1. METHODS: Using immunohistochemistry we compared expression patterns of alpha1beta1, alpha2beta1 und alpha3beta1 in normal skin and keloid tissue. Secondly, the effect of TGF-beta1-antisense after 48 h and 72 h incubation in a keloid-derived fibroblast monolayer was analyzed by means of reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry. RESULTS: alpha1beta1 and alpha2beta1 were highly expressed in keloid fibroblasts. Incubation with TGF-beta1-antisense lead to a reduction on protein level. RT-PCR demonstrated an increase of all alpha subunits, while on an mRNA level a decrease of the subunit beta1 could be observed. CONCLUSION: Integrin expression is directly modulated by TGF-beta1. An abnormal response in the keloid as a result of an altered TGF-beta1 pathway could be a key element to understanding the development of keloids.

TGF-beta1 antisense therapy modulates expression of matrix metalloproteinases in keloid-derived fibroblasts.

Transforming growth factor-beta1 (TGF-beta1) has been identified as an important regulator of wound healing. Recent developments in molecular therapy offer exciting prospects for the modulation of wound healing, specifically those targeting TGF-beta1. The purpose of this study was to analyze the effect of TGF-beta1 targeting on the expression of matrix metalloproteinases (MMPs) in fibroblasts cultured from earlobe keloids. The expression of MMP-2 and -9 in tissue samples from keloids was investigated by immunohistochemistry. The effect of TGF-beta1 targeting using antisense oligonucleotides on the expression of MMPs in keloid-derived fibroblasts was analysed by ELISA and multiplex RT-PCR. Immunohistochemical studies demonstrated an increased expression of MMP protein in tissue samples from keloids compared to normal human skin. Antisense TGF-beta1 oligonucleotide treatment significantly downregulated MMP-9 secretion in vitro. In conclusion, TGF-beta1 antisense oligonucleotide technology may be a potential therapeutic option for the inhibition of proteolytic tissue destruction in keloids.

Long-term results of inferior turbinate reduction with argon plasma coagulation.

OBJECTIVES: Surgical reduction of the inferior turbinates is a commonly used therapy in patients with hyperplastic inferior turbinates when medical management remains ineffective. Current surgical methods have disadvantages (e.g., necessity of nasal packing, extended postoperative swelling, and high costs). Theoretical considerations render argon plasma coagulation (APC) a promising new therapeutic approach. STUDY DESIGN: In a prospective study, 121 patients with chronic nasal obstruction were treated for inferior turbinate reduction with APC. Hyperplasia of the nasal turbinates was diagnosed rhinoscopically and endoscopically and confirmed rhinomanometrically. The mean follow-up period was 12 months, ranging from 10 to 16 months. The treatment results were evaluated by a questionnaire, rhinomanometric findings, and electron microscopic studies of the nasal mucosa. In 50 patients a ciliary function test was performed preoperatively and postoperatively. METHODS: Argon plasma coagulation, a high-frequency electrosurgery, has been used for volume reduction of the inferior turbinate in local anesthesia. RESULTS: Seventy-six percent of the patients reported an improvement of the postoperative swelling within the first week. After 6 weeks, macroscopically the turbinates were re-epithelialized by normal mucosa in 63% of the patients. Electron microscopic studies after 3 months verified normal cilia. After 12 months, 83% of the patients stated that they had a better nasal airflow than preoperatively. Crust formation was minimal. No bleeding or impaired ciliary function occurred. Ninety-five percent of the patients were willing to undergo the same operation again. CONCLUSION: The long-term results have proved APC to be an effective and easy-to-perform alternative for inferior turbinate reduction with comparable results to other established surgical methods.

Role of surgery in the management of head and neck cancer: a contemporary view of the data in the era of organ preservation.

OBJECTIVE: Review of the literature on the role of surgery in the management of head and neck cancer in the era of organ preservation. METHOD: Literature search based on the essential practice guidelines set out by the US National Comprehensive Cancer Network. RESULTS: Despite the increasing popularity of non-surgical treatment options, the surgeon remains a key figure in the multidisciplinary head and neck cancer team, along with the radiation oncologist, the medical oncologist and the speech and swallowing therapist. Even when organ preservation is successful, early and late toxicity may cause serious complications, including laryngeal dysfunction with a 'frozen larynx'. When organ preservation fails, salvage surgery is often associated with increased complications and reduced survival. CONCLUSION: There is a definite need to apply more rigorous standards to the use of organ preservation strategies, and to re-evaluate the role of surgery in head and neck cancer treatment.

Induction chemotherapy with TPF (Docetaxel, Carboplatin and Fluorouracil) in the treatment of locally advanced squamous cell carcinoma of the head and neck.

Squamous cell carcinoma of the head and neck (SCCHN) presents at a locally advanced (LA) stage in many patients. Chemotherapy, which is one fundamental therapy mode for local disease control of inoperable disease or if organ preservation is desired, has become an important factor of first line treatment regimens either during or prior to radiotherapy (RT). Patients with locoregionally advanced inoperable, recurrent or metastatic disease still have a poor prognosis, which enforces the need for new treatment approaches and new drug therapies, adjusted to the different settings of the disease. One innovative progress for this collective of patients with locally advanced tumor was the implementation of Docetaxel in chemotherapeutic regimes in optimal combination with concurrent chemoradiotherapy or in neoadjuvant setting of induction phase treatment. Docetaxel combined with the conventional chemotherapy regimen, containing Cisplatin and 5-Fluorouracil (TPF), is now acknowledged as being the gold standard of induction treatment. Various studies suggest survival advantage due to the induction chemotherapy (ICT) followed by chemoradiotherapy, which is known as sequential therapy, over chemoradiotherapy alone. In contrast to prevailing studies we administered Docetaxel, Carboplatin and 5-FU within the frame-work of induction chemotherapy instead of conventional use of Cisplatin for five patients with locoregionally advanced HNSCC. The clinical progress was evaluated through cross section imaging (computer tomography/MRI) prior and after ICT and classified following the RECIST criteria. Due to a very small collective of patient and the administration of Carboplatin instead of Cisplatin in this study, it was not possible to document the the efficacy of ICT (TPF) concerning survival advantage in patient with locoregionally advanced head and neck tumors. Further studies with an extended collective of patients are neccessary.

[Middle-ear adenoma]. / Adenom des Mittelohres.

In our case we present a 47-year old female patient, who had a history of one year of right-sided recurrent ear pain without any signs of ear-infections. A computer tomography (CT) imaging was carried out. At the mid-modiolar level, the axial CT-scan showed a small contrast-enhancing density in the middle ear space. She refused further investigation until the ear-pain increased and slight hearing loss was present. Again, six months later a CT-scan was performed, and the hyperdense tissue formation engaged the entire middle ear cleft of the right temporal bone. Typical of MEA, no osteolytic signs were present; the skull-base was intact, the air-cell system of the temporal bone showed no osteolysis or deficiency. In the case presented here, we show a MEA which has filled the middle ear with fluid retention in the mastoid with absent destruction of any structure clinically resulting in ear pain and slight conductive hearing loss. These lesions are contrast-enhancing on CT and on magnetic resonance imaging (MRI) have brain-like signal intensity T2-weighted images. In this case, the lesion was exenterated.

[A comparison of the gene expression patterns of human chondrocytes and chondrogen differentiated mesenchymal stem cells for tissue engineering]. / Vergleich der Genexpressionsmuster humaner Chondrozyten und chondrogen differenzierter mesenchymaler Stammzellen für das Tissue-Engineering.

BACKGROUND: Tissue engineering is a promising method for the generation of chondrogenic grafts for reconstructive surgery. In cultured chondrocytes, the dedifferentiation of cells seems unavoidable for multiplication. METHODS: In this study, we investigated the expression of distinct markers during the dedifferentiation of human chondrocytes (HC) harvested during septoplasty and human mesenchymal stem cells (hMSC) from cartilage biopsies in cell culture using the microarray technique. RESULTS: The genes for collagen 1alpha1, 2alpha1, 3alpha1, 4alpha1, 11alpha1, biglycan, fibromodulin and lumican were activated during the dedifferentiation of the HCs, collagen 9alpha2, 9alpha3, 10alpha1 and chondroadherin were inactivated. During chondrogenic differentiation of hMSCs, the genes for collagen 3alpha1, 9alpha2, 9alpha3, 10alpha1, 11alpha1 were activated, collagen 4alpha1 and fibromodulin inactivated and the genes for Col 1alpha1, biglycan und chondroadherin constantly expressed. CONCLUSION: The genetic profile for the investigated markers in human chondrocytes generated from hMSCs resembles the profile in differentiated chondrocytes. Collagen 2alpha1, 9alpha2, 9alpha3, 10alpha1 could represent markers for the differentiation of chondrocytes, Col 1alpha1, 3alpha1 und 4alpha1, biglycan, fibromodulin and lumican markers for the dedifferentiation into a more fibroblastoid cell type.

[Current therapeutic options for recurrent respiratory papillomatosis]. / Aktuelle Therapieoptionen bei der rezidivierenden respiratorischen Papillomatose.

The purpose of this review is to describe and to critically discuss recent advances in the management of recurrent respiratory papillomatosis (RRP). The goal of surgery in RRP remains the control of symptoms. A curative therapy cannot be expected. The microdebrider and the CO(2)-laser are currently the most widely used surgical options. Literature reports an increase in adjuvant medical therapies of 10-22%. The most common drugs in adjuvant therapy are interferon, cidofovir and indole-3-carbinole/diindolylmethane. The lack of controlled studies limits our ability to accurately assess the antiviral action of the adjuvant therapies. At the moment, therapeutic interventions remain focused on the surgical removal of papillomas when possible, and additional adjuvant therapy is available for the minority of patients for whom surgical management fails to adequately control their disease. Recent advances in immunologic research offer the hope of immune system modulation as potential future treatment modalities to better control this disease process.

[Tonsillotomy with the argon-supported monopolar needle--first clinical results]. / Tonsillotomie mit der argonunterstützten, monopolaren Nadel--erste klinische Erfahrungen.

BACKGROUND: Primary management of tonsillar hyperplasia in children is tonsillectomy. Recent data from clinical case-series are clearly in support of the hypothesis that tonsillotomy with the CO2-laser seems to be effective and is noted to have less postoperative bleeding and less pain as compared to tonsillectomy. For the first time we used a monopolar argon-supported needle for tonsillotomy in the following study. METHODS: Fifty patients (age: 4.58 years; SD +/- 2.33) with benign tonsillar hyperplasia were recruited. For tonsillotomy we used the monopolar argon-supported needle. The outcome measures were postoperative pain, capability of oral intake, consumption of analgesics and postoperative bleeding. RESULTS: No postoperative bleeding occurred. Post-operative pain hardly occurred and could easily be controlled. The third postoperative day analgesics intake was under one portion per day (mean: 0.91; SD +/- 1.26). Capability of oral intake and swallowing was normal on the seventh postoperative day. CONCLUSION: It was concluded that tonsillotomy, using the monopolar argon-supported needle, is a valid treatment for benign tonsillar hyperplasia in children, which can be performed with slight post-operative pain and a low risk for postoperative bleeding. It offers good dissection and haemostasis abilities. Compared to the CO2-laser the monopolar argon-supported needle does not require any laser safety precautions.

[Angiogenic factors in external auditory canal cholesteatoma-fibroblast cell culture]. / Angiogene Faktoren in der Fibroblastenzellkultur des Gehörgangcholesteatoms.

BACKGROUND: The external auditory canal cholesteatoma (EACC) is characterized by hyperproliferation of the epithelial and subepithelial tissue. Compared to normal meatal skin, strong expression of FGF-2 and VEGF had previously been detected. Many authors reported that FGF-2 acts via VEGF and is induced by hypoxia. Hypoxia seems to be pivotal for establishing EACC. Therefore, human EACC fibroblasts were investigated by incubating with FGF-2 and determining VEGF. PATIENTS AND METHODS: We harvested fibroblasts from human EACC and normal meatal skin and incubated the fibroblast culture with 50 ng/ml FGF-2 and determined VEGF concentrations after 1-4 days. RESULTS: Compared to untreated fibroblast cultures, there was a significant increase of VEGF concentration (p<0.05). However, there was no significant difference between the proliferation quantities. CONCLUSION: VEGF and FGF-2 are possibly involved in a cascade of growth factor activities, which modulates their concentration in human-derived EACC fibroblast culture. Exogenous FGF-2 increased fibroblast expression for VEGF, which is a major autocrine mediator of FGF-2-induced angiogenesis and proliferation.

[Physiology, role and neuropharmacology of yawning]. / Physiologie, Rolle und Neuropharmakologie des Gähnens.

Yawning is a physiological event that can be divided into three distinct phases: a long inspiratory phase, a brief acme and a rapid exspiration. The reason for yawning is not yet well defined. However this semi-voluntary event increases vigilance and aims to alert when drowsiness occurs. Yawning may have an important role for social communication. The neuropharmacology of yawning is complex and knowledge of its mechanisms is incomplete. While under the control of several neurotransmitters, yawning is largely affected by dopamine. Dopamine may activate oxytocin production in the paraventricular nucleus of the hypothalamus, oxytocin may then activate cholinergic neurotransmission in the hippocampus, and finally acetylcholine might induce yawning via the muscarinic receptors of the effectors. In fact, this scheme is simplified. Many other molecules can modulate yawning, such as nitric oxide, glutamate, GABA, serotonin, ACTH, MSH, sexual hormones and opium derivate peptides.

[Cell adhesion proteins in external auditory canal cholesteatoma]. / Expression von Zell-Zell-Adhäsionsproteinen im Gehörgangscholesteatom.

BACKGROUND: External auditory canal cholesteatoma (EACC) is a rare entity in otolaryngology, which is histomorphologically identical with middle ear cholesteatoma. The cause of EACCt is, however, still not clear. The aim of this study was to describe the expression of beta-catenin, MMP-2, and MMP-9 in EACC matrix compared to the normal auditory meatal skin (AMS). METHODS: Thirteen specimens were obtained during surgical procedure. EACC and AMS specimens were immunostained with antibodies for beta-catenin, MMP-2, and MMP-9. RESULTS: Only the basal layers of the EACC specimens were positive for beta-catenin. The suprabasal layers showed diminished or negative immunostaining for beta-catenin. In all layers, AMS was homogeneously positive for beta-catenin. In contrast, the immunostaining for the gelatinases was equally increased in all layers of EACC, whereas AMS was weekly positive. CONCLUSION: The reduced immunoreactivity for beta-catenin may have been present because of the lessened cell-cell adhesion in the suprabasal layers of EACC. The increased expression of the metalloproteinases might point at an increased lack of integrity of EACC matrix. Recent studies revealed a balance between disintegrating and stabilising factors in normal tissue, which is disturbed in inflamed and neoplastic tissue. In EACC matrix, an imbalance of these factors, represented by reduced beta-catenin and increased gelatinase expression, is possible. Increased desquamation, the accumulation of keratin debris, and loss of tissue-stability support our findings.

[Argon plasma coagulation and topically applied estriol. Long-term results in the treatment of hereditary hemorrhagic telangiectasia of the nasal mucosa]. / Argonplasmachirurgie und topische Estriolapplikation. Langzeitergebnisse in der Behandlung von hereditären hämorrhagischen Teleangiektasien der Nasenschleimhaut.

BACKGROUND AND OBJECTIVE: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant fibrovascular dysplasia with the main symptom of recurrent epistaxis. At present, only limited data are available on long-term results in the treatment of epistaxis. A part from the surgical treatment of the bleeding telangiectasia with argon plasma, an additional postoperative long-term treatment with estriol nose-ointment was performed and the results were analysed. PATIENTS AND METHODS: 69 patients with HHT were treated with APC and estriol nose ointment. 43 patients could be examined over a follow-up period of more than 20 months. The bleeding frequency and intensity as well as the patient's satisfaction with the treatment result were evaluated and the serum estriol level determined. RESULTS: After more than 20 months, the bleeding frequency and intensity were reduced in 95% of the patients compared to their preoperative findings. Under the influence of estriol, former berry-like telangiectasias became flatter and more even. Neither systemic side effects under topically applied estriol nor a relevant increase of serum estriol levels were observed. CONCLUSION: The combined treatment regimen with APC and topically applied estriol provides a new treatment concept of epistaxis in HHT.