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BACKGROUND:Head and neck squamous cell carcinoma (HNSCC) is considered to be a progressive disease resulting from alterations in multiple genes regulating cell proliferation and differentiation like receptor tyrosine kinases (RTKs) and members of the fibroblast growth factor receptors (FGFR)-family. Single-nucleotide polymorphism (SNP) Arg388 of the FGFR4 is associated with a reduced overall survival in patients with cancers of various types. We speculate that FGFR4 expression and SNP is associated with worse survival in patients with HSNCC. AIM:To investigate the potential clinical significance of FGFR4 Arg388 in the context of tumors arising in HNSCC, a comprehensive analysis of FGFR4 receptor expression and genotype in tumor tissues and correlated results with patients' clinical data in a large cohort of patients with HNSCC was conducted. METHODS:Surgical specimens from 284 patients with HNSCC were retrieved from the Institute of Pathology at the Ludwig-Maximilian-University in Germany. Specimens were analyzed using immunohistochemistry and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The expression of FGFR4 was analyzed in 284 surgical specimens of HNSCC using immunohistochemstry. FGFR4 polymorphism was detected by PCR-RFLP. Patients' clinical data with a minimum follow-up of 5 years were statistically evaluated with a special emphasis on survival analysis employing Kaplan-Meier estimator and Cox regression analysis. RESULTS:Concerning the invasive tumor areas the intensity of the FGFR4 expression was evaluated in a four-grade system: no expression, low expression, intermediate and high expression. FGFR4 expression was scored as "high" (+++) in 74 (26%), "intermediate" (++) in 103 (36.3%), and "low" (+) in 107 (36.7%) cases. Analyzing the FGFR4 mutation it was found in 96 tumors (33.8%), 84 of them (29.6%) having a heterozygous and 12 (4.2%) homozygous mutated Arg388 allele. The overall frequency concerning the mutant alleles demonstrated 65% vs 34% mutated alleles in general. FGFR4 Arg388 was significantly associated with advanced tumor stage (P < 0.004), local metastasis (P < 0.0001) and reduced disease-free survival (P < 0.01). Furthermore, increased expression of FGFR4 correlated significantly with worse overall survival (P < 0.003). CONCLUSION:In conclusion, the FGFR4 Arg388 genotype and protein expression of FGFR4 impacts tumor progression in patients with HNSCC and may present a useful target within a multimodal therapeutic intervention. CA - Bergmann

Carcinoma of unknown primary is defined as the histological diagnosis of metastasis without the detection of a primary tumor. In the literature, the incidence of CUP in all patients with a malignant disease is said to be between 3% and 15%. The most frequent histopathological results of CUP metastases are adenocarcinoma, followed by undifferentiated carcinoma and squamous cell carcinoma. In this retrospective investigation the clinical records of 167 patients were studied. All patients had been admitted and treated for cervical CUP at the Department of Otorhinolaryngology of the Grosshadern Clinic from 1979 to 1998. Cervical swelling was the first noted symptom in all cases, followed by pain and dysphagia. The study group comprised 134 men and 33 women with an average age of 55 years at admission. Squamous cell carcinoma (n=123) was the predominant histopathological finding of the cervical lymph nodes. During the 10-year follow-up, a primary tumor was detected in 36 (21.5%) of the 167 initially diagnosed CUP patients. In over 90% of these cases the tumor was localized in the head and neck region. The most frequent origin of the tumor was the tonsilla palatina (n=7). Neck dissection and additional postoperative radiotherapy was performed in 118 (70.7%) of the 167 CUP patients. Primary radiotherapy was the treatment of choice in 28 patients; eight patients received combined radio-chemotherapy as the primary treatment and seven patients were treated with chemotherapy alone. Six patients had no treatment. Comparison of different treatment protocols revealed a significant difference in patient survival: in comparison with primary radiotherapy alone or neck dissection and postoperative radiotherapy, the survival rate improved significantly in patients that received a bilateral tonsillectomy in addition to neck dissection and postoperative radiotherapy. The treatment of choice in patients with cervical CUP should be a surgical procedure including (radical) neck dissection and diagnostic bilateral tonsillectomy followed by postoperative radiation of the cervical lymph drainage. Bilateral tonsillectomy is especially important and is correlated with a significant improvement of the survival rate in CUP patients. Additional postoperative radiation of the entire pharyngeal and laryngeal mucosa should also be considered in order to treat a possible small primary tumor in this region.

Background Carcinoma of unknown primary is defined as histological diagnosis of metastasis without diagnosis of a primary tumor. The incidence of CUP is stated in the literature between 3 % and 15 % of all patients with an malignant disease. Histological examination of CUP-metastasis of the neck most frequently shows a squamous cell carcinoma. A retrospective study of patient data was undertaken. Patients and methods The study included 167 patients admitted and treated for cervical CUP at the department of Oto-Rhino-Laryngology, Klinikum Grosshadern from 1979 to 1998. Cervical swelling was the first noted symptom in all cases. Other symptoms were pain and dysphagia. Of the 167 patients 134 were men and 33 were women. The average age at admission was 55 years. In the studied collective squamous cell carcinoma had the highest incidence (n = 123). During the 10 year follow-up a primary tumor was found in 36 of the 167 initially diagnosed CUP-patients. In over 90 % of these cases the tumor was localized in the head and neck region. The origin of the tumor was most frequently the tonsilla palatina (n = 7). Of the 167 patients included in the study 118 patients (70,7 %) underwent surgery and additional postoperative radiotherapy. Primary radiotherapy was the treatment of choice in 28 patients, 8 patients received combined radio-chemotherapy as primary treatment and 7 patients were treated with chemotherapy alone. No treatment was performed in 6 patients. Results By comparing the treatment methods there was a significant difference of patient survival in regard to the treatment. Patients treated according to treatment-plan II, which includes an additional "diagnostic" tonsillectomy, is significantly higher than that of patients simply undergoing neck dissection and postoperative radiotherapy or primary radiotherapy alone. Treatment of choice in patients with cervical CUP should be a surgical procedure including radical neck dissection and diagnostic bilateral tonsillectomy followed by postoperative radiation of the cervical lymph drainage. Discussion Bilateral tonsillectomy is especially important and is correlated with a significant improvement of the survival rate in CUP patients. Additional postoperative radiation of the pharynx from the base of the skull to the upper oesophagus should also be considered, in order to treat a possible--small--primary tumor in this region.

Background: Patients with gastroesophageal reflux disease (GERD) may suffer from a large variety of symptoms in the upper aerodigestive tract such as globus sensation, chronic cough, hoarseness and many others. Diagnosis and causal therapy may sometimes be difficult with gastroenterologic evaluation sometimes revealing no pathologic result. The objective of this study was to determine the impact of 24-hour intraesophageal pH monitoring with 2 channels (gastric and laryngeal) in the diagnosis of reflux-induced otolaryngologic disorders. Methods: This study included 22 patients presenting to the Department of Otolaryngology with symptoms like chronic cough (n = 3), globus sensation and dysphagia (n = 11), heartburn (n = 2), hoarseness and dysphonia (n = 2) or burning sensation of the tongue (n = 1). Three patients had a pathologic formation in the glottic area (leukoplakia, granuloma, polyp). All patients underwent a otolaryngological examination, a gastroenterological investigation and a 24-hour intraesophageal pH monitoring with 2 channels. Results: All 22 patients showed laryngeal mucosal lesions (posterior laryngitis). The gastroenterological evaluation with esophagogastroduodenoscopy was normal in 4 cases. 13 patients showed a hiatal hernia, 4 patients were suffering from a reflux-esophagitis grade I and 2 patients from grade Il. One patient had an erythema and 5 patients showed erosions of the gastric mucosa. Seven patients had more than one of the above mentioned diagnoses. Intraesophageal pH-monitoring with 2 channels over 24 hours revealed a gastroesophageal reflux of all 22 patients and a high reflux to the laryngeal level of 21 patients, probably causing laryngopharyngeal symptoms. Therapy of the patients consisted of medical antireflux treatment with proton pump inhibitor esomeprazol (Nexium®, 40 mg, 1-0-0). Within 4 weeks 15 of 22 patients had no more laryngopharyngeal symptoms or at least a significant reduction. Conclusion: Patients with laryngopharyngeal symptoms such as hoarseness, globus sensation or dysphagia can suffer from GERD, even if typical symptoms such as heartburn or retrosternal pain do not exist and gastroesophageal intervention reveals a normal result. The best diagnostic instrument for the diagnosis of reflux-induced otolaryngologic disorders is a 24-hour intraesophageal pH-monitoring with 2 channels (measure-points at the distal esophagus and laryngeal level). Medical antireflux treatment should consist of proton pump inhibitors (e.g. Nexium®) in a dose of 40 mg per day over at least 4 weeks.

Microcystic adnexal carcinoma is a rare cutaneous neoplasm characterized by slow but locally aggressive growth, which normally does not lead to systemic metastasis. Frequent local recurrences are reported, which are most likely due to insufficient operative technique. We present the fourth case of cervical ipsilateral metastatic microcystic adnexal carcinoma in an otherwise healthy woman. The patient presented with a previously diagnosed but not completely resected microcystic adnexal carcinoma in the area of the right posterior scalp and two palpable ipsilateral lymph nodes. The tumor was resected using intraoperative snap frozen histological evaluation of the resection borders. In the same procedure two lymph nodes were resected from the right neck. The lymph nodes were histologically assessed and showed infiltration by small strains of tumor cells. After exclusion of a second primary tumor, e.g., mammary carcinoma, as the cause for cervical lymph node metastases, we performed a modified radical neck dissection with resection of the sternocleidomastoid muscle and the accessory nerve, which was histologically proven to be perineurally infiltrated by tumor cells. In this second procedure the histological evaluation of the specimen showed no sign of remaining tumor infiltration. After exclusion of distant metastasis the patient was irradiated with 60 Gy. The patient is well 1 year after the initial treatment without signs of recurrence.

For a long time heartburn was not considered a symptom for serious illness. By now, however, it is accepted that the incidence of secondary carcinoma of the esophagus caused by chronic GERD has increased dramatically since the nineteen-seventies. Mechanisms leading to GERD are complex and its incidence is not necessarily pathological. However pathological reflux in the lower esophagus (pH lower than 4 in 6 % of 24 hours), caused by decreased sphinctertonus, impaired peristalsis and clearance of the esophagus, may lead to complications. Helicobacter pylori may play a key role in GERD. There is strong evidence for a protective effect of Hp-infection in the development of GERD. In pangastritis, caused by Hp-infection, gastric acid production is inhibited resulting in a reduction of stomach-acid-concentration. This may be caused by either the chronic infection itself and the resulting atrophy of the stomach-mucosa, by the ammonia-producing HP-bacteria, or an increase in acid re-absorbtion of gastric epithelium. Laryngopharyngeal reflux (LPR) often results in atypical manifestations with oral, pharyngeal, laryngeal, and pulmonary disorders. Laryngopharyngeal reflux is known to contribute to posterior acid laryngitis and laryngeal contact ulceration or granuloma formation, laryngeal cancer, chronic hoarseness, pharyngitis, asthma, pneumonia, nocturnal choking, and dental diseases. Today, PPI are the medication of choice in both acute and long-term (prophylactic) therapy of GERD. The so called "step-up-strategy" of medication is no longer recommended. Here, patients were first treated with antacids, then prokinetics followed by H2-blockers and finally low-dose PPI. Only in the case of persisting symptoms medication was further increased to high-dose PPI therapy. In the past this increase in medication lead to a prolonged healing process and consequently to higher medication costs. Studies have shown that a "step-down"-therapy, beginning with high dose PPI, is highly preferable, since it is much more effective. Depending on the degree of the symptoms, however, medication may also be applied "on-demand". The BfArM has approved this kind of medication application only for Esomeprazol (Nexium mups 20 mg).

BACKGROUND 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 done through 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. METHODS We performed reverse transcription PCR from 29 tissue specimens of squamous cell carcinomas and one melanoma and 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 RARalpha, beta, gamma and RXRalpha. RESULTS Only RARgamma was expressed 100 % in cell lines and tissue specimens. RARbeta showed a 100 % expression only in tissue specimens whereas a 54 % expression in cell lines was seen. All other receptors were diminished in their expression. In the positive controls all receptors were expressed 100 %. CONCLUSION The expression of RARalpha and RARbeta was partially lost in cell lines established from squamous cell carcinoma of the head and neck. The 100 % expression of RARbeta in tissue samples versus 54 % in cell lines can be explained by 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 RARalpha and beta play a pivotal role in mediating the response to retinoids.

Background Gastroesophageal reflux disease (GERD) is associated with a wide spectrum of otolaryngologic disorders and extraesophageal complications of the upper aerodigestive tract. Previous studies of patients diagnosed with GERD have reported symptoms such as asthma, chronic cough, pneumonia, laryngitis, but also other oral, rhinopharyngeal and laryngeal disorders, e.g. sore throat, globus sensation, and hoarseness. The objective of this study was to determine the incidence of gastroenterologic diseases in patients complaining of upper aerodigestive, pulmonary, laryngeal, pharyngeal, oral, and cervical disorders that are possibly attributable to GERD. Patients This study included 40 patients, who presented to the department of Otolaryngology with chronic complaints of at least one of the following symptoms or disorders during a minimum period of 3 months: dysphagia (n = 28), sensation of globus pharyngeus (n = 28), hoarseness (n = 20), odynophagia (n = 22), heartburn (n = 16), postnasal drip (n = 15), sore throat (n = 22), cough (n = 14), throat clearing (n = 11), laryngospasm (n = 6), and voice fatigue (n = 6). A complete examination of the head and neck was performed. Inflammatory disorders of the nose and the paranasal sinuses could not be confirmed by history, nasal endoscopy and Water's view x-ray or CT-scan of the paranasal sinuses in all patients. Results The main otorhinolaryngologic findings were laryngeal lesions (n = 38), including posterior laryngitis, erythema and edema of the interarytenoideal region, and chronic hyperplastic laryngitis. All patients were referred for gastroenterologic evaluation, where esophagogastroduodenoscopy was performed with histological examination of biopsy specimens. Different gastroenterologic diseases such as GERD, gastritis and hiatal hernia were confirmed in 30 of 40 cases, and appeared solely or in combination with each other. GERD was the most frequent gastroenterologic disease (48%), followed by hiatal hernia (45%) and Helicobacter pylori positive antrum gastritis (23%). Patients with GERD were treated with medical antireflux therapy, e.g. 20 mg to 40 mg of the proton pump inhibitor omeprazole daily. There was a remarkably good therapeutic outcome, since laryngeal disorders and findings as the result of gastroenterologic diseases resolved in 29 out of 30 patients. To date, these therapeutic results were maintained for the mean follow-up period of 8 months. Conclusions It is concluded that in many patients, suffering from the above-mentioned otolaryngologic symptoms, occult gastroesophageal diseases are present. However, laryngoscopic findings are subtle and meticulous examination is mandatory. Medical antireflux treatment is effective for relief of symptoms and mucosal healing. Thus, extraesophageal otolaryngologic symptoms and laryngeal manifestations are to be considered as extragastrointestinal manifestations mainly of reflux disease.

The aim of photodynamic diagnostics is complete visualization of all neoplastic lesions in a tumorous organ after the application of a tumor-selective photosensitizer. We explored the potential benefit of a combination of retinyl palmitate for the treatment of oral leukoplakias and follow-up diagnosis of malignant tissue by using 5-aminolevulinic acid (5-ALA) as a fluorescence marker. Semiquantitative measurements were performed following the topical application of 5-ALA in six patients. After biopsy and histological evaluation of tissue specimens the patients were treated with escalating doses of retinyl palmitate. After treatment periods ranging from 4 to 8 weeks 5-ALA was again applied for photodetection of persisting fluorescence. In all cases prior to retinyl palmitate treatment a prominent red fluorescence indicated tissue dysplasia. Eight weeks after treatment with retinyl palmitate decreased red fluorescence intensities were found, and repeated histological evaluations showed no persistent signs of dysplastic lesions. Our initial experience shows that high doses of retinyl palmitate can be useful for treating dysplastic lesions in the upper aerodigestive tract and can be monitored with 5-ALA induced protoporphyrin IX fluorescence.

BACKGROUND Rhinoscleroma is a rare infectious disease of the upper respiratory tract caused by Klebsiella rhinoscleromatis. The nasal mucosa represents the primary region of occurrence which is most likely a result of respiratory transmission. Without adequate++ treatment, the disease can potentially spread to the rest of the upper and middle respiratory tract within a period of several years. Healing often occurs with extensive scarring and adhesions of the nose, palate and larynx. A life threatening late stage manifestation includes subglottic stenosis requiring immediate surgical intervention. Medical treatment primarily consists of a long-term course of antibiotics. Ciprofloxacin (Fluoroquinolon) has proved to be one of the most effective drugs. CASE REPORT We report about a 33 year-old Egyptian male, who presented in our department with a 10 year history of a previously, only temporarily successfully treated rhinoscleroma. His main symptoms were nasal obstruction, epistaxis and inspiratory stridor. FINDINGS We began treatment with Ciprofloxacin over a four week period, which lead to an improvement of his symptoms. The treatment was considered complete after several biopsies and smears were negative for live specimens. We then chose to reduce the scar tissue that was causing obstruction in the larynx and the nose. CONCLUSION The rhinoscleroma is a rare disease in geographic areas with poor hygiene and can mimic several other infectious and malignant diseases. Treatment should include a long-term antimicrobial therapy and surgical intervention in cases with symptomatic obstruction.

Background Solitary intraparotid facial neurofibromas are extremely rare. These tumours arise from Schwann cells, in most cases as a manifestation of neurofibromatosis. In an intraparotid localisation, they can mimic other parotideal tumours. Due to their slow growth, they may be clinically inapparent for a long time. Case report We present the case of a patient with a right intraparotid neurofibroma originating from the facial nerve. He noted a slight facial weakness for the last three years and dullness over the preauricular area. On operation, all facial nerve branches were incorporated in the tumour mass. A total resection via monitoring technique of facial nerve function was performed. Postoperatively, the patient suffered from an incomplete facial palsy. Conclusion This case highlights particularly the importance of a concise diagnostic work-up of every facial palsy. Precise histological diagnosis is particularly essential because of the different biological behaviour of neurofibromas in contrast to neurinomas. With preoperative facial palsy the chance of facial nerve preservation decreases. Clinical and operative experience with parotid gland neurofibromas shows that recovery of facial nerve defects is mostly incomplete.

BACKGROUND 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, the epidermal growth factor receptor (EGFR). METHODS Using molecular biological techniques, we examined the incidence of TGF-alpha and EGFR expression in 43 patients with tumors of the head and neck. The expression data were correlated with the course of disease in four-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). RESULTS An expression for the TGF-alpha protein was only detected in group 4. There was a significant correlation with EGFR overexpression in group 4 and survival compared with group 3 (p < 0.01) and group 1 (p < 0.05). The mean survival for group 1 to 4 was 27, 33, 34, and 10 months, respectively. CONCLUSION The analysis of all patients revealed that the patients with synchronous expression of EGFR and 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 preventive therapies.

Laryngeal leukoplakia can be a premalignant precursor of squamous cell carcinoma, is often tobacco-related and can usually be readily monitored by indirect laryngoscopy. One of the main motivations for using retinyl palmitate in patients with persistent leukoplakia was to avoid general anesthesia for elderly patients, who are considered to be high-risk patients when direct larynoscopy is required for possible tissue biopsy. Our study was the first to investigate the effectiveness and toxicity of high-dose retinyl palmitate in the treatment of laryngeal leukoplakia. Treatment was divided into two phases. In the first phase, all patients underwent induction therapy with 300,000 IU/day of retinyl palmitate for the 1st week, which was then adjusted up to 1,500,000 IU/day in the 5th week in patients with resistant lesions. Patients whose lesions progressed during this period were withdrawn from the study. In the second phase, patients whose lesions responded to treatment or remained stable were assigned to a maintenance therapy of 150,000 IU/day. Complete remission was observed in 15 of 20 patients (75% of cases). Partial response was seen in the remaining 5 patients, with 3 of the patients relapsing. The median duration of treatment and follow-up was 18 months (range, 12-24 months). These results indicate that retinyl palmitate has substantial activity in laryngeal leukoplakias. Since only minor side effects were seen, the medication is an excellent candidate as a preventive agent for laryngeal cancer.

Background. Larynx leukoplakia can be a premalignant precursor of squamous cell carcinoma, is often tobacco related, and can be monitored easily by indirect laryngoscopy. One of the main motivations for using retinyl palmitate in patients with larynx leukoplakia was to avoid general anesthesia for the elderly patients, who are considered to be at high risk for undergoing direct laryngoscopy. Our study investigates for the first time the effectiveness and toxicity of high-dose retinyl palmitate in the treatment of larynx leukoplakia. Methods. Treatment was divided into two phases. In the first phase, all patients underwent induction therapy with a high-dose of retinyl palmitate (A-Mulsin Hochkonzentrat, Mucos Pharma, Geretsried, Germany) with 300,000 IU/day for the first week and up to 1,500,000 IU/day, in patients with resistant lesions, in the fifth week. Patients whose lesions progressed during this period were withdrawn from the study. In the second phase, patients whose lesions responded to treatment or remained stable were then assigned to a maintenance therapy of 150,000 IU/day. Results. We observed a complete remission rate of 75% (15 of 20 patients). Among the 5 patients with partial response, 3 relapsed. The median duration of treatment and follow up was 18 months (range 12-24 months). Conclusions. These results indicate that retinyl palmitate has substantial activity in larynx leukoplakias. Furthermore, only minor side effects make it an excellent candidate as a preventive agent for larynx cancer.

In order to test methods of predicting skin flap viability, a skin flap model in Sprague-Dawley rats was established. As criteria for studying skin flap survival, we compared measurement of skin pH, temperature, as well as fluorescence photography and computer aided digital morphometry (CADM). Ninety male Sprague-Dawley rats were divided into three groups in which pedicles were clamped for 10, 15, or 20 h. A standardized bipedicled skin flap was prepared, maintained by the epigastric artery, vein and nerve. All flaps were sutured back in place immediately after clamping. We found that postoperative prediction of flap survival based solely upon external appearance was impossible until the 2nd postoperative day. Changes in pH were not statistically significant in the prediction of vital or necrotic flaps. The temperature measurements showed, that in the event of viability the decrease in flap temperature versus the reference temperature (rectal temperature) was significant (P < 0.0094 in Group II, 15 h of ischaemia) or at least a tendency to significance (P < 0.059 in Group III, 10 h of ischaemia) bigger than in the event of partial or total flap necrosis. The photographic documentation using fluorescein showed that all coloured areas survived. Group I (20 h) showed predominantly total flap necrosis. Most flaps in Group III (10 h) exhibited a small necrotic area at the tip. In Group II (15 h) no typical staining pattern could be observed. Furthermore, computer aided digital morphometry demonstrated a decrease of the necrotic area by 7% between the 2nd and 4th postoperative day in Groups II and III. The method which gave the most exact prediction about viability was the fluorescein staining of the flaps via the tail vein.

BACKGROUND Leukoplakia, a white patch in the oral cavity or in the larynx that cannot be scraped off is a premalignant precursor of squamous cell carcinoma. It is tobacco-related and easily monitored. The rate of transformation of leukoplakia into invasive cancer is directly related to the degree of histologic abnormality. In the largest and longest study in the United States (mean follow-up, 7.2 years), the long-term transformation rate for dysplastic lesions was 36%. Surgical removal is considered the best therapy. However many patients operated on for oral leukoplakia later develop local relapses, new leukoplakias, or squamous cell carcinoma. Although leukoplakia lesions can show spontaneous regression, the response rate observed under treatment of retinoids is much greater. METHODS In our study, high-dose retinyl palmitate was used for the first time on leukoplakias of the larynx. The study was conducted in two phases. In the first phase, all patients underwent induction therapy with a high dose of Retinyl Palmitate (A-Mulsin Hochkonzentrat, Mucos Pharma, Geretsried, Germany) 300.000 IU daily for the first week up to 1,500,000 IU daily in the fifth week. Patients whose lesions progressed during this period were withdrawn from the study. In the second phase, patients whose lesions responded to treatment or remained stable were then assigned to a maintenance therapy. The median duration of treatment was 104 days (range 15-272). RESULTS We observed a complete remission rate of 65% (20 out of 31 patients), a partial remission in 8 patients (26%) and a relaps in three patients (9%) during the next 15 months follow-up. Relapses were mainly seen in patients with a history of a carcinoma in situ or squamous cell carcinoma. CONCLUSIONS One of the main reasons for using retinyl palmitate in patients with larynx leukoplakia was to avoid general anesthesia in elderly patients who were considered as high risk patients for undergoing surgery. These results indicate that retinyl palmitate has substantial activity in larynx premalignancy. Because of its minor toxicity, it is an excellent candidate for a preventive agent for larynx cancer.

Introduction: The interstitial deletion of chromosome 5q is a disease of rare incidence, which might be hereditary or caused by spontaneous changes within the chromosome respectively. The pathology is based on the loss of chromosomal material within the long arm of chromosome 5. Clinical manifestations are mainly known in hematology, particular such as malignancies or hematopoetic malformation. Other morphological characteristics that have been described following deletion of chromosome 5q are deformity of the skull and the joints as well as heart defects. In the following we will present some pathologic findings focussing on the head and neck. Patient: We introduce a young female patient of 8 months with deletion of the long arm of chromosome 5q. In addition to the known skeletal and hematopoetic disorders we discovered a unilateral deafness and a contralateral middle-graded combined hearing-loss as well as laryngomalacia. Conclusion: Infants with chromosome 5 syndrome should undergo an otorhinolaryngological examination to investigate anatomic malformations. In particular a brainstem electric response audiometry should be considered for early diagnosis and treatment of a possible hearing-loss. This ensures adequate and early support of the patients physical and psychological development.

Neurogenic tumours of the larynx, particularly schwannomas are rare. We report a case report of a schwannoma in a 30-year-old woman which was excised endoscopically. The aim of this paper is to highlight this rare condition and management options to the otolaryngological community.

Salivary leakage can be a major symptom of valve failure or incorrect positioning of indwelling voice rehabilitation valves in a tracheo-oesophageal fistula. Usually, removal of the valve for a short time leads to shrinking of the fistula or a simple valve replacement procedure resolves the problem. If the fistula, however, does not close spontaneously, symptoms persist and the fistula may have to be closed surgically. In a retrospective study, data of 103 patients who underwent laryngectomy and primary voice rehabilitation between 1989 and 1998 with either the Provox or the Eska-Herrmann prosthesis were compared with regard to surgical fistula closure requirement. A total of 55 patients underwent laryngectomy and primary voice rehabilitation with the Eska-Herrmann and 48 with the Provox prosthesis. Initial tumour treatment also included post-operative radiotherapy for all patients in the study. In total, surgical fistula closure had to be performed in three patients, all of whom had been treated with the Provox prosthesis. The time span between initial voice rehabilitation and surgical closure of the fistula was 5 months, 21 months and 24 months in all three patients respectively. None of the fistulas developed in relation to recurring tumour disease. The Provox prosthesis seem to have a higher risk of developing fistulas necessitating surgical intervention, even years after initial tumour therapy, than the Eska-Herrman prosthesis. These complications may be due to the larger tracheo-oesophageal fistula necessary to fit the larger diameter of the Provox prosthesis.

The Wiskott-Aldrich-syndrome belongs to the phakomatoses. The hereditary transmission happens x-chromosomal recessive in the domain of Xp 11.3-Xp 11.22. Clinical evidence for that is given by thrombocytopenia, an eczema and a weakness of the immune system with a subsequent increased risk of frequent infections and a predisposition for a malignancies. A further characteristic of that disease is recurrent otitis media as described by Aldrich in 1954.The case--as described above--is about a 28-year-old male patient developing an acute deafness on the left ear while he has been suffering from a surditas on the right ear for 5 years. 8 years ago a splenectomy was made, because of persistent thrombocytopenia. An additional clinical characteristic was a hemiballism, arising after a thalamusbleeding 5 years ago, a both-sided vestibular failure concerning both that has been existing for 2 years, as well as a maculopathia with a highly reduced visus on both sides.The deafness arising in patients suffering from the Wiskott-Aldrich-syndrome represents a so far not described symptom of that illness.

BACKGROUND The occurrence of metastasis of renal cell carcinomas in the head and neck region is extremely rare. Metastasis in the larynx, hypopharynx, and the nasal sinuses has been reported. We report here about a 55-year-old female with metastasis in the soft palate and tonsil, which occurred 10 years following tumor nephrectomy. RESULTS AND CONCLUSIONS The incidence of metastasis in renal cell carcinomas can be observed even many years following initial curative treatment of the primary tumor. Although rare in the region of the head and neck, they can often be mistaken for benign tumors such as hemangiomas or inflammatory tissue. The treatment of choice is radical surgical resection.

INTRODUCTION In 1967, Kleinsasser first reported about basal cell adenomas in salivary glands, which represent approximately 1-2% of all salivary gland tumors. About 70% of these tumors are found in the parotid gland. Less often the minor salivary glands are involved, particularly in the upper lip region. We would like to report on a case of occurrence in the upper pole of the palatine tonsil. CASE REPORT A 68-year-old woman was seen, who complained about a growth in her left tonsil. Other than a slow increase size, she had no symptoms. Examination revealed a solid tumor approximately 3 cm in diameter which displaced the upper part of the tonsil medially. In an MRI study, the neoplasia demonstrated a low signal intensity in the T1-weighted images and a high signal intensity in the T2-weighted images, which is relatively typical for a cystic structure. The tumor extended to the base of skull, and was completely resected by extended tonsillectomy. Histologic studies showed a cystic, regressive basal cell adenoma. DISCUSSION When compared to pleomorphic adenomas, basal cell adenomas are relatively rare in the region of the soft palate. This case is especially interesting because we assume the origin of the tumor to be in the supratonsillar salivary glands (Weber's glands) and also because of the unusually pronounced cystic regressive changes.

Carcinoma of unknown primary is defined as histological diagnosis of metastasis without diagnosis of a primary tumor. The incidence of CUP is stated in the literature between 3 % and 15 % of all patients with an malignant disease. Histological examination of CUP-metastasis of the neck most frequently shows a squamous cell carcinoma. A retrospective study of patient data was undertaken.The study included 167 patients admitted and treated for cervical CUP at the department of Oto-Rhino-Laryngology, Klinikum Grosshadern from 1979 to 1998. Cervical swelling was the first noted symptom in all cases. Other symptoms were pain and dysphagia. Of the 167 patients 134 were men and 33 were women. The average age at admission was 55 years. In the studied collective squamous cell carcinoma had the highest incidence (n = 123). During the 10 year follow-up a primary tumor was found in 36 of the 167 initially diagnosed CUP-patients. In over 90 % of these cases the tumor was localized in the head and neck region. The origin of the tumor was most frequently the tonsilla palatina (n = 7). Of the 167 patients included in the study 118 patients (70,7 %) underwent surgery and additional postoperative radiotherapy. Primary radiotherapy was the treatment of choice in 28 patients, 8 patients received combined radio-chemotherapy as primary treatment and 7 patients were treated with chemotherapy alone. No treatment was performed in 6 patients.By comparing the treatment methods there was a significant difference of patient survival in regard to the treatment. Patients treated according to treatment-plan II, which includes an additional "diagnostic" tonsillectomy, is significantly higher than that of patients simply undergoing neck dissection and postoperative radiotherapy or primary radiotherapy alone. Treatment of choice in patients with cervical CUP should be a surgical procedure including radical neck dissection and diagnostic bilateral tonsillectomy followed by postoperative radiation of the cervical lymph drainage.Bilateral tonsillectomy is especially important and is correlated with a significant improvement of the survival rate in CUP patients. Additional postoperative radiation of the pharynx from the base of the skull to the upper oesophagus should also be considered, in order to treat a possible--small--primary tumor in this region.

Gastro-oesophageal reflux disease (GORD) refers to the symptoms and complications of abnormal passage of gastric contents into the oesophagus. Symptoms of GORD commonly include heartburn and acid regurgitation. Apart from this typical presentation of GORD, extra-oesophageal reflux disease often results in oral, pharyngeal, laryngeal and pulmonary disorders.1 Laryngopharyngeal reflux is the movement of gastric contents beyond the oesophagus up to the laryngeal and pharyngeal area. As well as pepsin and acid, gastric contents can include bile acids and pancreatic enzymes, all of which can injure tissues not adapted to them. Laryngopharyngeal reflux is known to contribute to posterior laryngitis, laryngeal contact ulcerations, laryngeal and pharyngeal cancer,2 subglottic stenosis and laryngospasm, dysphonias, pharyngitis, asthma, pneumonia, nocturnal choking and dental diseases.3

Patients with gastroesophageal reflux disease (GERD) may suffer from a large variety of symptoms in the upper aerodigestive tract such as globus sensation, chronic cough, hoarseness and many others. Diagnosis and causal therapy may sometimes be difficult with gastroenterologic evaluation sometimes revealing no pathologic result. The objective of this study was to determine the impact of 24-hour intraesophageal pH monitoring with 2 channels (gastric and laryngeal) in the diagnosis of reflux-induced otolaryngologic disorders.This study included 22 patients presenting to the Department of Otolaryngology with symptoms like chronic cough (n = 3), globus sensation and dysphagia (n = 11), heartburn (n = 2), hoarseness and dysphonia (n = 2) or burning sensation of the tongue (n = 1). Three patients had a pathologic formation in the glottic area (leukoplakia, granuloma, polyp). All patients underwent a otolaryngological examination, a gastroenterological investigation and a 24-hour intraesophageal pH monitoring with 2 channels.All 22 patients showed laryngeal mucosal lesions (posterior laryngitis). The gastroenterological evaluation with esophagogastroduodenoscopy was normal in 4 cases. 13 patients showed a hiatal hernia, 4 patients were suffering from a reflux-esophagitis grade I and 2 patients from grade II. One patient had an erythema and 5 patients showed erosions of the gastric mucosa. Seven patients had more than one of the above mentioned diagnoses. Intraesophageal pH-monitoring with 2 channels over 24 hours revealed a gastroesophageal reflux of all 22 patients and a high reflux to the laryngeal level of 21 patients, probably causing laryngopharyngeal symptoms. Therapy of the patients consisted of medical antireflux treatment with proton pump inhibitor esomeprazol (Nexium, 40 mg, 1-0-0). Within 4 weeks 15 of 22 patients had no more laryngopharyngeal symptoms or at least a significant reduction.Patients with laryngopharyngeal symptoms such as hoarseness, globus sensation or dysphagia can suffer from GERD, even if typical symptoms such as heartburn or retrosternal pain do not exist and gastroesophageal intervention reveals a normal result. The best diagnostic instrument for the diagnosis of reflux-induced otolaryngologic disorders is a 24-hour intraesophageal pH-monitoring with 2 channels (measure-points at the distal esophagus and laryngeal level). Medical antireflux treatment should consist of proton pump inhibitors (e. g. Nexium) in a dose of 40 mg per day over at least 4 weeks.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor of the skin characterized by frequent local and regional recurrence, a high incidence of distant metastases and therefore a high mortality. Here, we report a case of an oropharyngeal metastasis of a Merkel cell carcinoma of the skin localized at the left base of the tongue causing dysphagia and the sensation of globus pharyngeus. The unusual metastatic site is presented, and diagnosis and treatment are discussed.

For a long time heartburn was not considered a symptom for serious illness. By now, however, it is accepted that the incidence of secondary carcinoma of the esophagus caused by chronic GERD has increased dramatically since the nineteen-seventies. Mechanisms leading to GERD are complex and its incidence is not necessarily pathological. However pathological reflux in the lower esophagus (pH lower than 4 in 6 % of 24 hours), caused by decreased sphinctertonus, impaired peristalsis and clearance of the esophagus, may lead to complications. Helicobacter pylori may play a key role in GERD. There is strong evidence for a protective effect of Hp-infection in the development of GERD. In pangastritis, caused by Hp-infection, gastric acid production is inhibited resulting in a reduction of stomach-acid-concentration. This may be caused by either the chronic infection itself and the resulting atrophy of the stomach-mucosa, by the ammonia-producing HP-bacteria, or an increase in acid re-absorbtion of gastric epithelium. Laryngopharyngeal reflux (LPR) often results in atypical manifestations with oral, pharyngeal, laryngeal, and pulmonary disorders. Laryngopharyngeal reflux is known to contribute to posterior acid laryngitis and laryngeal contact ulceration or granuloma formation, laryngeal cancer, chronic hoarseness, pharyngitis, asthma, pneumonia, nocturnal choking, and dental diseases. Today, PPI are the medication of choice in both acute and long-term (prophylactic) therapy of GERD. The so called "step-up-strategy" of medication is no longer recommended. Here, patients were first treated with antacids, then prokinetics followed by H2-blockers and finally low-dose PPI. Only in the case of persisting symptoms medication was further increased to high-dose PPI therapy. In the past this increase in medication lead to a prolonged healing process and consequently to higher medication costs. Studies have shown that a "step-down"-therapy, beginning with high dose PPI, is highly preferable, since it is much more effective. Depending on the degree of the symptoms, however, medication may also be applied "on-demand". The BfArM has approved this kind of medication application only for Esomeprazol (Nexium mups 20 mg).

The interstitial deletion of chromosome 5q is a disease of rare incidence, which might be hereditary or caused by spontaneous changes within the chromosome respectively. The pathology is based on the loss of chromosomal material within the long arm of chromosome 5. Clinical manifestations are mainly known in hematology, particular such as malignancies or hematopoetic malformation. Other morphological characteristics that have been described following deletion of chromosome 5q are deformity of the skull and the joints as well as heart defects. In the following we will present some pathologic findings focussing on the head and neck.We introduce a young female patient of 8 months with deletion of the long arm of chromosome 5q. In addition to the known skeletal and hematopoetic disorders we discovered a unilateral deafness and a contralateral middle-graded combined hearing-loss as well as laryngomalacia.Infants with chromosome 5 syndrome should undergo an otorhinolaryngological examination to investigate anatomic malformations. In particular a brainstem electric response audiometry should be considered for early diagnosis and treatment of a possible hearing-loss. This ensures adequate and early support of the patients physical and psychological development.

Objectives The prevalence of gastroesophageal reflux disease (GERD) in patients with laryngopharyngeal disorders is probably greater than realized. Study Design Prospective study. Methods To investigate the incidence of gastroenterological diseases including GERD in patients complaining of nonspecific laryngopharyngeal symptoms, laryngological examinations and gastroenterological evaluation with esophagogastroduodenoscopy were performed in 30 patients who refused to undergo 24-hour pH monitoring. Therapeutic intervention by behavioural and dietary modifications, antireflux medication, and eradication of Helicobacter pylori were assessed for changes in laryngeal findings and relief of symptoms. Results Posterior laryngitis was present in 26 patients and in 19 of them was accompanied by erythema and edema of the interarytenoid region. Gastroenterological diseases such as GERD (43%), hiatal hernia (43%), and Helicobacter pylori-positive antrum gastritis (23%) were confirmed in 22 (73%) cases by esophagogastroduodenoscopy and histological examination of biopsy specimens. Medical antireflux treatment and eradication of Helicobacter pylori resulted in a remarkably therapeutic success rate of 90% because there was resolution of laryngopharyngeal symptoms and laryngeal findings in 20 of 22 patients with gastroenterological diseases for the mean follow-up period of 8 months. Conclusions Laryngopharyngeal symptoms can be predictors of gastroesophageal diseases and GERD because the most frequent underlying cause is supposed to be associated with posterior laryngitis. Medical antireflux treatment is effective for relief of symptoms and mucosal healing of posterior laryngitis.

Gastroesophageal reflux is now a generally accepted risk factor for the development of adenocarcinoma of the esophagus. Less well known is the relationship of reflux disease (GERD) and respiratory disorders. Among the extra-esophageal manifestations of reflux disease is reflux laryngitis, which affects up to 78 patients with chronic hoarseness, Reinke's edema, laryngeal stricture, postnasal drip, asthma and non-cardiac chest pain. Despite popular opinion, changes in lifestyle (for example, cessation of smoking and drinking, avoidance of fatty foods) do not result in an improvement in symptoms. The treatment of choice for GERD is the use of proton pump inhibitors (PPI) in the form of stepdown therapy; in individual cases as symptom-orientated on-demand therapy.

The intratympanic application of ototoxic antibiotics and saccotomia have been well documented in severe cases of one-sided Menière's disease for 30 years now. Both treatment methods are still subject to controversial discussion.This study includes 8 patients suffering from persistent one-sided Menière's disease after treatment with gentamicin application and additional saccotomia (n=2). We performed follow-up visits including the assessment of hearing ability, vestibular function and cranial MRI, 2-10 years after onset of treatment.After therapeutic interventions 7 patients reported to be healed of their symptom vertigo. In 4 patients the gentamicin-treated vestibular organ did not respond to thermic stimulus at the time of follow-up examination. Auditory threshold shift was observed in 3 patients (1 permanent, 2 temporary), whereas hearing threshold improved in 2 patients. Tinnitus was attenuated in 3 patients, while 1 patient suffered from posttherapeutic onset of tinnitus. Morphological and structural changes due to Menière's disease and treatment procedures were ruled out by cranial MRI.The intratympanic application of ototoxic medication is a safe and effective treatment method in severe cases of Menière's disease. Saccotomia should be considered as therapeutic regimen for persistent symptoms after repeated application of gentamicin.

We report a case of a 30-year-old, previously healthy man who presented at our clinic with complaints of increasing dysphagia and globus sensation for about 2 years. In addition, he noticed an increasing submental swelling. On examination, the patient revealed a massive swelling of the floor of the mouth, which had displaced the tongue cranially. MRI imaging showed the lesion to be a homogeneous, cystic lesion, clearly at a distance from the surrounding mucous tissue. Surgery was performed, and the tumor was resected completely. Histologic examination of the resected tissue was consistent with a dermoid cyst located in the floor of the mouth. Although dermoid cysts are rarely located in the oral cavity, it should be included in differential diagnosis. Surgery is the treatment of choice.

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 done through 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 and 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 RARalpha, beta, gamma and RXRalpha.Only RARgamma was expressed 100 % in cell lines and tissue specimens. RARbeta showed a 100 % expression only in tissue specimens whereas a 54 % expression in cell lines was seen. All other receptors were diminished in their expression. In the positive controls all receptors were expressed 100 %.The expression of RARalpha and RARbeta was partially lost in cell lines established from squamous cell carcinoma of the head and neck. The 100 % expression of RARbeta in tissue samples versus 54 % in cell lines can be explained by 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 RARalpha and beta play a pivotal role in mediating the response to retinoids.

Gastroesophageal reflux disease (GERD) is associated with a wide spectrum of otolaryngologic disorders and extraesophageal complications of the upper aerodigestive tract. Previous studies of patients diagnosed with GERD have reported symptoms such as asthma, chronic cough, pneumonia, laryngitis, but also other oral, rhinopharyngeal and laryngeal disorders, e.g. sore throat, globus sensation, and hoarseness. The objective of this study was to determine the incidence of gastroenterologic diseases in patients complaining of upper aerodigestive, pulmonary, laryngeal, pharyngeal, oral, and cervical disorders that are possibly attributable to GERD.This study included 40 patients, who presented to the department of Otolaryngology with chronic complaints of at least one of the following symptoms or disorders during a minimum period of 3 months: dysphagia (n = 28), sensation of globus pharyngeus (n = 28), hoarseness (n = 20), odynophagia (n = 22), heartburn (n = 16), postnasal drip (n = 15), sore throat (n = 22), cough (n = 14), throat clearing (n = 11), laryngospasm (n = 6), and voice fatigue (n = 6). A complete examination of the head and neck was performed. Inflammatory disorders of the nose and the paranasal sinuses could not be confirmed by history, nasal endoscopy and Water's view x-ray or CT-scan of the paranasal sinuses in all patients.The main otorhinolaryngologic findings were laryngeal lesions (n = 38), including posterior laryngitis, erythema and edema of the interarytenoideal region, and chronic hyperplastic laryngitis. All patients were referred for gastroenterologic evaluation, where esophagogastroduodenoscopy was performed with histological examination of biopsy specimens. Different gastroenterologic diseases such as GERD, gastritis and hiatal hernia were confirmed in 30 of 40 cases, and appeared solely or in combination with each other. GERD was the most frequent gastroenterologic disease (48%), followed by hiatal hernia (45%) and Helicobacter pylori positive antrum gastritis (23%). Patients with GERD were treated with medical antireflux therapy, e.g. 20 mg to 40 mg of the proton pump inhibitor omeprazole daily. There was a remarkably good therapeutic outcome, since laryngeal disorders and findings as the result of gastroenterologic diseases resolved in 29 out of 30 patients. To date, these therapeutic results were maintained for the mean follow-up period of 8 months.It is concluded that in many patients, suffering from the above-mentioned otolaryngologic symptoms, occult gastroesophageal diseases are present. However, laryngoscopic findings are subtle and meticulous examination is mandatory. Medical antireflux treatment is effective for relief of symptoms and mucosal healing. Thus, extraesophageal otolaryngologic symptoms and laryngeal manifestations are to be considered as extragastrointestinal manifestations mainly of reflux disease.

Rhinoscleroma is a rare infectious disease of the upper respiratory tract caused by Klebsiella rhinoscleromatis. The nasal mucosa represents the primary region of occurrence which is most likely a result of respiratory transmission. Without adequate++ treatment, the disease can potentially spread to the rest of the upper and middle respiratory tract within a period of several years. Healing often occurs with extensive scarring and adhesions of the nose, palate and larynx. A life threatening late stage manifestation includes subglottic stenosis requiring immediate surgical intervention. Medical treatment primarily consists of a long-term course of antibiotics. Ciprofloxacin (Fluoroquinolon) has proved to be one of the most effective drugs.We report about a 33 year-old Egyptian male, who presented in our department with a 10 year history of a previously, only temporarily successfully treated rhinoscleroma. His main symptoms were nasal obstruction, epistaxis and inspiratory stridor.We began treatment with Ciprofloxacin over a four week period, which lead to an improvement of his symptoms. The treatment was considered complete after several biopsies and smears were negative for live specimens. We then chose to reduce the scar tissue that was causing obstruction in the larynx and the nose.The rhinoscleroma is a rare disease in geographic areas with poor hygiene and can mimic several other infectious and malignant diseases. Treatment should include a long-term antimicrobial therapy and surgical intervention in cases with symptomatic obstruction.

Relapsing polychondritis is a rare inflammatory disease that causes destruction of cartilaginous tissue in various anatomical regions. We report here about a 55-year-old female patient with relapsing polychondritis that involved the right auricle, both audiovestibular organs and both eyes. The patient presented with persisting inflammation of the right auricle, sudden lower-frequency hearing loss, acute moderate vertigo with nausea and mild ocular symptoms. Immunofluorescence assays were used for the detection of antibodies against the cochlea and the vestibular organ and demonstrated the presence of circulating antibodies against the audiovestibular organ. No staining for anti-corneal IgG was detected. Improvement of clinical disease was achieved by treatment with systemic steroids and vasodilator drugs, and long-term medication with low-dose corticosteroids.

Solitary intraparotid facial neurofibromas are extremely rare. These tumours arise from Schwann cells, in most cases as a manifestation of neurofibromatosis. In an intraparotid localisation, they can mimic other parotideal tumours. Due to their slow growth, they may be clinically inapparent for a long time.We present the case of a patient with a right intraparotid neurofibroma originating from the facial nerve. He noted a slight facial weakness for the last three years and dullness over the preauricular area. On operation, all facial nerve branches were incorporated in the tumour mass. A total resection via monitoring technique of facial nerve function was performed. Postoperatively, the patient suffered from an incomplete facial palsy.This case highlights particularly the importance of a concise diagnostic work-up of every facial palsy. Precise histological diagnosis is particularly essential because of the different biological behaviour of neurofibromas in contrast to neurinomas. With preoperative facial palsy the chance of facial nerve preservation decreases. Clinical and operative experience with parotid gland neurofibromas shows that recovery of facial nerve defects is mostly incomplete.

The occurrence of metastasis of renal cell carcinomas in the head and neck region is extremely rare. Metastasis in the larynx, hypopharynx, and the nasal sinuses has been reported. We report here about a 55-year-old female with metastasis in the soft palate and tonsil, which occurred 10 years following tumor nephrectomy.The incidence of metastasis in renal cell carcinomas can be observed even many years following initial curative treatment of the primary tumor. Although rare in the region of the head and neck, they can often be mistaken for benign tumors such as hemangiomas or inflammatory tissue. The treatment of choice is radical surgical resection.

In 1967, Kleinsasser first reported about basal cell adenomas in salivary glands, which represent approximately 1-2% of all salivary gland tumors. About 70% of these tumors are found in the parotid gland. Less often the minor salivary glands are involved, particularly in the upper lip region. We would like to report on a case of occurrence in the upper pole of the palatine tonsil.A 68-year-old woman was seen, who complained about a growth in her left tonsil. Other than a slow increase size, she had no symptoms. Examination revealed a solid tumor approximately 3 cm in diameter which displaced the upper part of the tonsil medially. In an MRI study, the neoplasia demonstrated a low signal intensity in the T1-weighted images and a high signal intensity in the T2-weighted images, which is relatively typical for a cystic structure. The tumor extended to the base of skull, and was completely resected by extended tonsillectomy. Histologic studies showed a cystic, regressive basal cell adenoma.When compared to pleomorphic adenomas, basal cell adenomas are relatively rare in the region of the soft palate. This case is especially interesting because we assume the origin of the tumor to be in the supratonsillar salivary glands (Weber's glands) and also because of the unusually pronounced cystic regressive changes.

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, the epidermal growth factor receptor (EGFR).Using molecular biological techniques, we examined the incidence of TGF-alpha and EGFR expression in 43 patients with tumors of the head and neck. The expression data were correlated with the course of disease in four-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).An expression for the TGF-alpha protein was only detected in group 4. There was a significant correlation with EGFR overexpression in group 4 and survival compared with group 3 (p0.01) and group 1 (p0.05). The mean survival for group 1 to 4 was 27, 33, 34, and 10 months, respectively.The analysis of all patients revealed that the patients with synchronous expression of EGFR and 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 preventive therapies.

Larynx leukoplakia can be a premalignant precursor of squamous cell carcinoma, is often tobacco related, and can be monitored easily by indirect laryngoscopy. One of the main motivations for using retinyl palmitate in patients with larynx leukoplakia was to avoid general anesthesia for the elderly patients, who are considered to be at high risk for undergoing direct laryngoscopy. Our study investigates for the first time the effectiveness and toxicity of high-dose retinyl palmitate in the treatment of larynx leukoplakia.Treatment was divided into two phases. In the first phase, all patients underwent induction therapy with a high-dose of retinyl palmitate (A-Mulsin Hochkonzentrat, Mucos Pharma, Geretsried, Germany) with 300,000 IU/day for the first week and up to 1,500,000 IU/day, in patients with resistant lesions, in the fifth week. Patients whose lesions progressed during this period were withdrawn from the study. In the second phase, patients whose lesions responded to treatment or remained stable were then assigned to a maintenance therapy of 150,000 IU/day.We observed a complete remission rate of 75% (15 of 20 patients). Among the 5 patients with partial response, 3 relapsed. The median duration of treatment and follow up was 18 months (range 12-24 months).These results indicate that retinyl palmitate has substantial activity in larynx leukoplakias. Furthermore, only minor side effects make it an excellent candidate as a preventive agent for larynx cancer.

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.

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 (p0.01) and group 1 (p0.05). 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).

Leukoplakia, a white patch in the oral cavity or in the larynx that cannot be scraped off is a premalignant precursor of squamous cell carcinoma. It is tobacco-related and easily monitored. The rate of transformation of leukoplakia into invasive cancer is directly related to the degree of histologic abnormality. In the largest and longest study in the United States (mean follow-up, 7.2 years), the long-term transformation rate for dysplastic lesions was 36%. Surgical removal is considered the best therapy. However many patients operated on for oral leukoplakia later develop local relapses, new leukoplakias, or squamous cell carcinoma. Although leukoplakia lesions can show spontaneous regression, the response rate observed under treatment of retinoids is much greater.In our study, high-dose retinyl palmitate was used for the first time on leukoplakias of the larynx. The study was conducted in two phases. In the first phase, all patients underwent induction therapy with a high dose of Retinyl Palmitate (A-Mulsin Hochkonzentrat, Mucos Pharma, Geretsried, Germany) 300.000 IU daily for the first week up to 1,500,000 IU daily in the fifth week. Patients whose lesions progressed during this period were withdrawn from the study. In the second phase, patients whose lesions responded to treatment or remained stable were then assigned to a maintenance therapy. The median duration of treatment was 104 days (range 15-272).We observed a complete remission rate of 65% (20 out of 31 patients), a partial remission in 8 patients (26%) and a relaps in three patients (9%) during the next 15 months follow-up. Relapses were mainly seen in patients with a history of a carcinoma in situ or squamous cell carcinoma.One of the main reasons for using retinyl palmitate in patients with larynx leukoplakia was to avoid general anesthesia in elderly patients who were considered as high risk patients for undergoing surgery. These results indicate that retinyl palmitate has substantial activity in larynx premalignancy. Because of its minor toxicity, it is an excellent candidate for a preventive agent for larynx cancer.

Die Bedeutung der Vitamine als essentielle Bestandteile unserer Ernahrung, steht heute auser Frage. Dennoch wird der Grundbedarf eines gesunden Menschen kontro­vers diskutiert. Angaben diesbezuglich differieren nicht selten um 10er-Potenzen. Bekannt ist, das unsere durchschnittliche Ernahrung den Tagesbedarf an fettloslichen Vitaminen haufig nicht decken kann und wir zudem durch die Belastung mit Schadstoffen und Stres einem erhohten Vitaminverbrauch unterliegen. Empfehlungen uber taglichen Vitamin-A-Grundbedarf von 5000 bis 10000 I.E. und einer prophylaktischen Dosis beispiels­weise bei Rauchern von 10000 bis 30000 sind, gemes­sen am heutigen Erkenntnisstand, nicht aus der Luft ge­griffen. Grundsatzlich ist zwischen Grundbedarf, Pro­phylaxe und Therapie, die eine deutliche hohere Dosie­rung erfordert, zu trennen.

Das Wachstum und die Differenzierung von malignen Tumorzellen wird von einer Vielzahl von Zytokinen beeinflust. Desweiteren zeigt die klinische Erfahrung, das sich histologisch gleichartige Tumoren mit gleicher Lokalisation und Ausdehnung biologisch haufig sehr unterschiedlich verhalten. Dies mag einerseits durch Patientenfaktoren andererseits durch Tumorfaktoren begrundet sein. Bezuglich der Tumorfaktoren sind von besonderer Bedeutung die Zytokine, die von den Tumorzellen selber abgegeben werden, die entweder direkt oder indirekt uber tumorinfiltrierende Lymphozyten oder Makrophagen das Tumorwachstum regulieren. Von besonderem Interesse sind Zytokine wie Interleukin-6 (IL-6) und LIF („leukemia inhibiting factor“), die das Wachstum und die Differenzierung von Tumorzellen und von immunkompetenten Zellen beeinflussen. Entsprechend den verschiedenen biologischen Wirkungen finden sich fur beide Proteine eine Vielzahl von Synonymen.