[Naturopathic therapy for acute otitis media. An alternative to the primary use of antibiotics]. / Naturheilkundliche Therapie der akuten Otitis media. Eine Alternative zum primären Antibiotikaeinsatz.

BACKGROUND: First line antibiotic treatment of uncomplicated acute otitis media has been questioned. PATIENTS AND METHODS: In an prospective, open, controlled study, 390 children aged 1-10 years were treated either conventionally (free combinations of decongestant nose drops, mucolytics, analgesics and antibiotics) or alternatively with Otovowen, supplemented by conventional medications when considered necessary. RESULTS: Patients treated conventionally took more antibiotics (80.5% vs 14.4%) and analgesics (66.8% vs 53.2%). The time to recovery (5.3 vs 5.1 days) and absence from school or pre-school nursery (both 1.7 days) were not significantly different between groups. Pain resolution was slightly better with conventional treatment (-5.8 vs -5.2 score points). The alternative treatment was judged both by doctors, and parents, to be significantly better tolerated. CONCLUSION: In uncomplicated acute otitis media of childhood, an alternative treatment strategy with the natural medicine Otovowen may substantially reduce the use of antibiotics without disadvantage to the clinical outcome.

Alternative versus conventional treatment strategy in uncomplicated acute otitis media in children: a prospective, open, controlled parallel-group comparison.

OBJECTIVES: Evidence from clinical trials questions the benefit-risk ratio of first-line antibiotic treatment for uncomplicated acute otitis media in childhood. Alternative treatment strategies are very popular but have not been the subject of larger controlled clinical trials. This trial compares an alternative with a conventional treatment strategy for acute otitis media. METHODS AND PATIENTS: 390 children aged 1-10 years presenting with uncomplicated acute otitis media participated in a prospective, open, non-randomized, controlled, parallel-group study. According to self-assignment of investigators, children were treated either conventionally (free combinations of decongestant nose drops, mucolytics, analgesics and antibiotics) or alternatively with Otovowen (fixed combination of plant-based tinctures and homeopathic potencies), supplemented by conventional medications when considered necessary. RESULTS: Alternatively treated patients (n = 192) had significantly less severe otoscopic findings and clinical symptom ratings at baseline than children treated in conventional centers (n = 193). Patients cared for by conventional therapists took more antibiotics (80.5% vs. 14.4%; chi2-test, p < 0.001) and analgesics (66.8% vs. 53.2%; chi2-test, p = 0.007). Times to recovery were 5.3 +/- 2.4 and 5.1 +/- 2.2 days for alternative and conventional treatment, respectively. Odds ratios (OR) with a lower limit of 1-sided 97.5% confidence interval (CI) were 0.98 (0.76), 0.95 (0.73) and 0.88 (0.69) for results adjusted to baseline otoscopy, pain and symptom score, respectively (Cox-Mantel test). Absence from school or preschool nursery was 1.7 days in both groups; ORs (CI) were 1.00 (0.76), 0.96 (0.73) and 1.04 (0.80). Noninferiority of alternative treatment (CI limit of OR above 0.696) was not proven for pain resolution (-5.2 vs. -5.8 score points); OR (CI) were 0.87 (0.68), 1.15 (0.87) and 0.74 (0.58). Alternative treatment was judged both by doctors (Mann-Whitney estimator with 2-sided 95% CI 0.41 (0.35-0.47)) and parents (0.42 (0.36-0.48)), to be significantly better tolerated than conventional treatment. CONCLUSIONS: In primary care management of uncomplicated acute otitis media in childhood, an alternative treatment strategy based on the natural medicine, Otovowen may substantially reduce the use of antibiotics without disadvantage to the clinical outcome.

Endoscopic cordectomy. A proposal for a classification by the Working Committee, European Laryngological Society.

The European Laryngological Society is proposing a classification of different laryngeal endoscopic cordectomies in order to ensure better definitions of post-operative results. We chose to keep the word "cordectomy" even for partial resections because it is the term most often used in the surgical literature. The classification comprises eight types of cordectomies: a subepithelial cordectomy (type I), which is resection of the epithelium; a subligamental cordectomy (type II), which is a resection of the epithelium, Reinke's space and vocal ligament; transmuscular cordectomy (type III), which proceeds through the vocalis muscle; total cordectomy (type IV); extended cordectomy, which encompasses the contralateral vocal fold and the anterior commissure (type Va); extended cordectomy, which includes the arytenoid (type Vb); extended cordectomy, which encompasses the subglottis (type Vc); and extended cordectomy, which includes the ventricle (type Vd). Indications for performing those cordectomies may vary from surgeon to surgeon. The operations are classified according to the surgical approach used and the degree of resection in order to facilitate use of the classification in daily practice. Each surgical procedure ensures that a specimen is available for histopathological examination.

Simultaneous radiochemotherapy versus radiotherapy alone in advanced head and neck cancer: a randomized multicenter study.

PURPOSE: A prospective randomized multicenter trial was performed to evaluate the contribution of simultaneously administered chemotherapy (CT) and radiotherapy (RT) in previously untreated patients with unresectable stage III/IV head and neck cancer. PATIENTS AND METHODS: Patients with locoregionally advanced head and neck cancer were treated either with RT alone (arm A) or simultaneous RT plus CT (RCT; arm B). RT was identical in both arms and administered in three courses with 13 fractions of 1.8 Gy each twice daily. During one course, from day 3 to 11, 23.4 Gy was delivered. In arm B, cisplatin (CDDP) 60 mg/m2, fluorouracil (5-FU) 350 mg/m2 by intravenous (i.v.) bolus, and leucovorin (LV) 50 mg/m2 by i.v. bolus were given on day 2, and 5-FU 350 mg/m2/24 hour by continuous infusion and LV 100 mg/m2/24 hours by continuous infusion were given from day 2 to 5. Treatment was repeated on days 22 and 44; a total RT dose of 70.2 Gy was administered. Treatment breaks were scheduled from days 12 to 21 and days 34 to 43. RESULTS: From 1989 to 1993, 298 patients were enrolled and 270 patients were assessable. Acute mucositis grade 3 or 4 was more frequent in arm B (38%) than in arm A (16%) (P < .001). Total treatment time was significantly longer in arm B than in arm A (P < .001) due to prolonged breaks. According to hematologic toxicity, scheduled drug doses were given in 74% of patients for the second course and 46% for the third course. The 3-year overall survival rate was 24% in arm A and 48% in arm B (P < .0003). The 3-year locoregional control rate was 17% in arm A and 36% in arm B (P < .004). Both arms showed similar distant failure patterns (arm A, 13 of 140; arm B, 12 of 130). Serious late side effects were not significantly different between treatment arms (arm A, 6.4%; arm B, 10%; not significant). CONCLUSION: Concomitant CT offered improved disease control and survival in advanced head and neck cancer patients. Due to increased acute toxicity, more supportive care is demanded when CT is given simultaneously. Increased total treatment time does not exert a negative impact on outcome in this combined modality regimen.

Expression of retinoic acid receptors in squamous cell carcinomas and their possible implication for chemoprevention.

Retinoic acid and its natural and synthetic analogs (retinoids) affect a wide array of biological processes. Retinoids are used in the treatment of many skin diseases and are promising drugs for several cancers. Most of their actions are thought to result from changes in gene expression which is caused via nuclear retinoic acid receptors and retinoid X receptors. We conducted a study to determine whether the expression of these receptors is different in malignant tumors and tumor cell lines versus normal tissue. We performed reverse transcription PCR from 29 tissue specimens of squamous cell carcinomas and one melanoma of the head and neck, as well as from 13 cell lines established from head and neck cancer. We were looking for the expression pattern of RAR alpha, beta, gamma and RXR alpha. Only RAR gamma was expressed 100% in cell lines and tissue specimens. RAR beta showed 100% expression in tissue specimens whereas 54% expression in cell lines was seen. All other receptors were diminished in their expression. In the positive controls all receptors were expressed at 100%. The expression of RAR alpha and RAR beta was partially lost in cell lines established from squamous cell carcinoma of the head and neck. The 100% expression of RAR beta in tissue samples versus 54% in cell lines can be explained by the clonal growth of malignant cells in cell lines and also possible "contamination" by normal cells in the tissue specimen. In concordance with the literature it seems that RARa and beta play a pivotal role in mediating the response to retinoids.

Causes of immunosuppression in squamous cell carcinoma of the head and neck.

Numerous dysfunctions of the immune system with prognostic relevance can be found in patients with SCCHN. The role of the different factors affecting the immune system has to be investigated in the future with particular consideration being given to the specific therapy indicated. Varying therapies modifying the immune system are available. It is necessary to clarify whether and how SCCHN patients can benefit from these forms of treatment and how dysfunctions of the immune system can be corrected without causing excessive reactions. From a surgical point of view one has to consider whether immune stimulation or reconstructive measures are indicated in patients with decreased immunity and whether less traumatic procedures with smaller blood loss may have a beneficial effect on the tumor's immunological situation, and therefore on the overall survival of the patient. The terms minimal-invasive or functional surgery may take on a new meaning as biologically-adjusted surgery, biologic preservative reconstructive surgery or biologically functional surgery. In SCCHN not only the radical removal of the primary tumor is of concern, but also the regional lymph nodes and their importance for other lymph nodes, the primary tumor and the immunity of the patient as a whole. These factors have to be taken into consideration in the therapeutic planning for the patient. Therapeutic efforts in SCCHN patients should therefore not only aim at the functional preservation of organs and at plastic reconstructive procedures but also preserve and, by biological immunotherapy, restore the tumor-specific immunity. This may result in better survival rates with better quality of life, even in complicated cases.

Comparison of migration and invasiveness of epithelial tumor and melanoma cells in vitro.

Tumor invasion of basement membranes is a complex multi-step process. Altered adhesion, as well as increased cell locomotion contribute to tumor cell invasion and metastasis. A variety of in vitro models have been used to measure cell invasiveness. The invasion of basement membranes can be simulated in vitro in blind well Boyden Chambers using the reconstituted basement membrane matrigel or collagen type I as the invasion barrier. The aim of our study was to compare the migration and invasive capacity of epidermal tumor cells (TR 131, TR 146, SCL II, FaDu, HLaC 79) and melanoma cells derived from primary tumors (Mel Ei, Mel Ho, Mel Juso, Mel Wei) or their metastases (Mel Ju, Mel Im, Sk Mel 1, Sk Mel 28). Chemotactic response of epidermal tumor cells was increased toward fibroblast conditioned medium and fibronectin (20 micrograms/ml), while laminin (100 micrograms/ml) stimulated chemotaxis in only 3 epidermal tumor cell lines (HLaC 79, FaDu, TR 146), EGF (10 ng/ml) in only 4 cases (SCL II, FaDu, TR 131, TR 146), and interleukin-1 (IL-1) in only 1 case (FaDu). Epithelial tumor cell conditioned medium had no chemotactic influence on epithelial tumor cells. Fibroblast conditioned medium, fibronectin, EGF and PDGF were potent chemoattractants for all melanoma tumor cells, whereas IL-1 did not induce a significant chemotactic response. While two epithelial tumor cell lines (FaDu, TR 146) were able to penetrate collagen type I, matrigel was an impenetrable barrier for all epithelial tumor cells. Two cell lines from melanoma primary tumors (Mel Ho, Mel Ei) and two cell lines from melanoma metastases (Sk Mel 1, Sk Mel 28) showed no invasion through collagen type I and matrigel, whereas invasion through both barriers could be observed for the metastatic cell lines Mel Ju and Mel Im and in the primary tumor cell line Mel Wei. Therefore, the clinical observation of late and rare metastasis in epithelial tumors and early metastasis in melanoma correlate with our in vitro investigation of invasive behavior in tumor cells. No significant correlation between the invasiveness of melanoma cell lines and their clinical origin could be demonstrated suggesting the existence of subpopulations with varying invasive potential.

Coexpression of epidermal growth factor receptor and TGF-alpha and survival in upper aerodigestive tract cancer.

In order to find a prognostic marker for the course of disease in head and neck cancer we hypothesized that patients with rapid disease progress would produce increased levels of transforming growth factor alpha (TGF-alpha) and its cell surface receptor, epidermal growth factor receptor (EGFR). Using molecular biological techniques, we examined the incidence of TGF-alpha and EGFR overexpression in 43 patients with tumors of the head and neck. The expression data was correlated with the course of disease in a 4 year follow-up. The tumors were classified into four groups according to the EGFR status: Group 1, no expression for EGFR (15 samples); group 2, expression level 10 for EGFR (18 samples); group 3, expression level 50 for EGFR (7 samples) and group 4, expression level 100 for EGFR (3 samples). Expression for the TGF-alpha protein was only detected in group 4. There was a significant correlation with EGFR/TGF-alpha overexpression in group 4 and survival compared when with group 3 (p < 0.01) and group 1 (p < 0.05). The mean survival for group 1 to 4 was 27, 23, 34 and 10 months, respectively. The analysis of all patients revealed that the patients who expressed EGFR as well as TGF-alpha had the poorest prognosis. Increased production of TGF-alpha and EGFR in tumors of the head and neck may serve both as a marker for tumor progression and as a target for therapy (e.g. inhibition of the autocrine loop, blockage of TGF-alpha binding).

Adenoma of the middle ear mucosa.

Benign adenomas of the middle ear are rare tumors. To date, approximately 100 cases of adenomatous neoplasms of the middle ear space have been collected in the United States Armed Forces Institute of Pathology, Washington D.C. This report describes two cases of primary adenomatous neoplasms confined to the middle ear cleft seen at the Department of Otorhinolaryngology at Ludwig Maximilians University Hospital, Munich. Although tumors are derived from lining epithelium of the middle ear mucosa, the unique feature of our first case was based on its origin in the epitympanic part of the tympanic membrane. Histopathology was characterized by an adenomatous morphology without atypia or mitoses, proving its benign behavior. No evidence was found for invasion of adjacent tissue. Simple surgical removal afforded excellent prognosis. Clinical behavior, histological appearance, origin of tumors and differential diagnosis are discussed.

Surgery of the internal nasal valve.

Over the past 25 years external rhinoplasty has become increasingly popular. Some rhinosurgeons recommend its use widely, even in routine cases. In our view, however, the classical endonasal approaches remain the first choice. Open rhinoplasty offers an excellent visualization and therefore facility of precise correction, but causes a larger area of wound and scarring. It should, therefore, be restricted to cases of particular difficulties. In the era of minimal invasive surgery, external rhinoplasty advocated as a standard procedure seems to be a drawback, particularly if the aesthetic problem is the leading one. Every facial plastic surgeon should master closed and external rhinoplasty to be able to decide which approach is the most suitable in each situation from the patient's point of view.

[Differential diagnosis of benign middle ear tumors]. / Zur Differentialdiagnose gutartiger Mittelohrtumoren.

Adenomas of the middle ear are quite rare tumours of the ear and of recent recognition. Two cases of adenomatous neoplasms confined to the middle ear are presented. Usually these tumours are located on the promontorium or in the hypotympanon. The unique feature of the first described case is based on its origin in the epitympanic pouch of the tympanic membrane. The second case originated from the mucosa in the hypotympanon. The third case is a tumour-like lesion which was not distinguishable on clinical grounds from a jugulo-tympanic paraganglioma or a middle ear adenoma. The adenomas of the middle ear are histopathologically characterised by differentiated glandular structures within fibrous tissue and recurrences are rarely observed. Surgical removal by the endaural route gives an excellent prognosis as shown by the literature and our own clinical cases.

[Rare complications of soft tissue infections in the head and neck area: deep neck phlegmona, thrombophlebitis and mediastinitis with pericardial effusion]. / Seltene Komplikationen von Weichteilinfekten im Kopf-Hals-Bereich: Tiefe Halsphlegmone, Thrombophlebitis und Mediastinitis mit Perikarderguss.

Cervical phlegmona is a rare occurrence associated with infections of the ENT region. Spreading of the infection can cause thrombophlebitis, mediastinitis and cardiac tamponade. Three recently treated patients are reported who showed serious complications due to harmless primary infections of the oral cavity, oropharynx or throat. The clinical course of the diseases with the sometimes difficult examinations undertaken and the performed treatment are outlined. Computed tomography and radiography of the lung were useful in confirming the diagnosis, establishing that the infection had spread into deep neck spaces and into the mediastinum. Surgical therapy including extensive surgical drainage of the deep neck spaces and of the mediastinum, multiple antibiotic therapy, and intensive care, resulted in survival of the patients.

Biology of interleukin-1 (IL-1), with respect to otorhinolaryngology-head and neck surgery.

Interleukin-1 (IL-1) has a number of fundamental immunoregulatory, hematologic, metabolic, and physiologic effects and thus is instrumental in the coordination of tissue interactions, such as wound healing, inflammation, and host tumor response. IL-1 stimulates the activation and differentiation of pre-B cells and T cells, chemotaxis of neutrophils, recruitment of bone marrow stem cells, stimulation of arachidonic acid metabolism, degradation of proteoglycans, and increase in basal body temperature. Altered production of IL-1 or IL-1 regulatory factors may have profound clinical consequences, such as seen in AIDS, other viral and malignant diseases, and in uncontrolled inflammatory processes. A variety of positive and negative feedback mechanisms for regulation of IL-1 production have been found; therapeutic interventions are aimed at these regulatory pathways. Through approaches interfering with the signal transduction or processing of IL-1, especially by interleukin-1-receptor antagonists (IL-1RA), future treatment modalities are on the horizon.

Heterologous epidermal growth factor receptor (EGF-R) expression in larynx cancer cell lines: evidence for the existence of structurally modified receptors.

Overexpression of epidermal growth factor receptor (EGF-R) is a common characteristic of epidermoid tumors and its expression in head and neck squamous cell carcinoma biopsies and cell lines has been reported previously by several authors. With the aim to provide more structural and functional details about the protein overexpression of EGF-R in head and neck squamous cell carcinomas, the expression of this molecule was studied in four larynx carcinoma cell lines (HLaC-78, HLaC-79, UM-SCC-17A and UM-SCC-17B). The results were compared with those from a spontaneously immortalized aneuploid human keratinocyte cell line (HaCaT) and cultured fresh skin keratinocytes. The EGF-R identification was performed using two well characterized monoclonal antibodies (MoAb) which recognize antigen determinants located on the extracellular domain of the receptor: EGF-R I and 29.1.1. Cytocentrifuge smears and cell suspensions were prepared for flow cytometric analysis. With the monoclonal antibody EGF-R I the highest EGF-R expression was obtained in the cell line UM-SCC-17A, whereas the cell line with the highest EGF-R overexpression was the HLa-C-78 if the monoclonal antibody 29.1.1 was used. The cultured keratinocytes always showed a histogram similar to the control sample (cells were incubated with the second antibody alone). These results could be explained by the existence of structurally modified EGF-receptors. Further studies including possible differences in both the autophosphorylization and the kinase activities are in progress to clarify the functional repercussions of these observed structural defects.