[Secondary polychondritis in Wegner's disease].
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Granulomatosis with Polyangiitis↗
Biomedical subjects
S Gottschlich
Publications and source records attributed to S Gottschlich.
Head and neck manifestations of Wegener's granulomatosis.
Wegener's Granulomatosis (WG) is a necrotizing granulomatous angiitis that presents the classic ELK triad of ear, nose, throat (E), lung (L), and kidney (K) involvement. Its potential rapid and fatal outcome makes the early recognition--before irreversible organ involvement occurs--mandatory. The aetiology is still unknown. Today, immunosuppressive therapy makes WG a treatable disease with a chronically relapsing course. The otorhinolaryngologist plays an important role in early diagnosis of WG, because in up to 95% of the patients initial WG symptoms are observed in the head and neck region. The majority of these patients show nasal or sinunasal involvement. Common manifestations are sinusitis, crusting of the nose, and development of saddle nose deformity. Other head and neck problems are middle and inner ear symptoms and subglottic stenosis. Follow up and activity assessment of the disease are also important roles to play for the otorhinolarygologist.
Biopsy↗
Sentinel lymph-node biopsy in head and neck cancer.
The aim of the study was to assess the diagnostic value of the sentinel node method in patients suffering from squamous cell carcinoma of the upper aerodigestive tract. In 50 patients with oral, pharyngeal or laryngeal carcinomas staged N0 up to 50 MBq technetium-99m colloid were injected peritumorally. Sentinel nodes were localised using a gamma-probe in the setting of an elective neck dissection. Pathological findings of sentinel nodes and corresponding neck specimens were compared. In 46 patients sentinel nodes were detected. Of these 34 patients were free of metastatic disease in the sentinel nodes and in the neck specimens. In 12 patients clinically occult metastases were found in the sentinel nodes. Three metastases were detected only after additional sectioning of the sentinel nodes. In four patients, a sentinel lymph node could not be localised. Our results support the sentinel node concept in head and neck cancer and a definition of the sentinel nodes as the three nodes with the highest activity. Careful clinical staging of the neck and thorough pathological evaluation of the sentinel nodes are necessary to avoid false-negative results.
Carcinoma, Squamous Cell↗
[Wegener's granulomatosis in the head and neck region].
Wegener's granulomatosis (WG) is defined as a granulomatous inflammation of the upper and lower respiratory tract and systemic vasculitis of small and medium sized vessels which is often accompanied by a necrotizing glomerulonephritis. The etiology of the disease is still unknown. In former times untreated WG usually ended deadly. Immunosuppressive therapy made WG a treatable disease with a chronically relapsing course. Therefore an early diagnosis of WG is of utmost importance. WG usually starts as a limited and localized organ manifestation in the upper respiratory tract and it generalizes, if untreated, with pulmonary and renal involvement. Symptoms in the head and neck region are observed in up to 95% of the patients with WG. Sinusitis, crusting of the nose, development of a saddle nose, middle and inner ear symptoms and subglottic stenosis are common manifestations. Due to the early and common manifestation of WG in the head and neck region the otorhinolaryngologist plays an important role for the early diagnosis and the fast initiation of immunosuppressive therapy but also during follow-up for activity assessment.
Aged↗
[Collagenase 3 mRNA expression in squamous epithelial carcinomas of the oropharynx].
BACKGROUND: Metalloproteinases (MMP) are endopeptidases, which are able to degrade extracellular matrix. It is assumed that MMP play an important role in invasion and metastasis of malignomas. The expression of collagenase-3, also named MMP-13, was already detected in squamous cell carcinoma of the head and neck, but the significance in the process of metastasis is still unclear. PATIENTS AND METHODS: 36 tumor biopsies of oropharyngeal squamous cell carcinoma (10 cases N0, 26 patients N+) and 12 biopsies of normal oropharyngeal mucosa were analysed with reverse transcriptase-PCR and Northern Blot for their mRNA-expression of MMP-13 and TIMP-1, the physiological inhibitor of MMP-13. RESULTS: In 30 of 36 (83.3%) tumor biopsies a MMP-13-mRNA-expression was detected. In 9 of 10 (90%) cases with N0-status and 21 of 26 (80.7%) cases with N(+)-neck the mRNA-expression could be shown. There was no correlation between MMP-13-mRNA-expression and N-status. In 34 tumor biopsies (94.4%) a TIMP-1-expression was detected. MMP-13-mRNA was not detected in normal oropharyngeal mucosa. CONCLUSIONS: It seems that MMP-13-mRNA-expression is not a prognostic factor for metastatic behavior of oropharyngeal cancer and therefore not helpful for further decisions on the therapy.
Adult↗
Experimental and clinical results of Er:YAG laser stapedotomy.
BACKGROUND AND OBJECTIVE: At the beginning of the 1980s, different laser types were used for stapes surgery to reduce potential harm to inner ear structures through manipulation with conventional instruments during stapedotomy. Most clinical studies were carried out with the CO2 or the argon laser. The Er:YAG laser has been used rarely in patients with otosclerosis. STUDY DESIGN/MATERIALS AND METHODS: In an experimental study on 54 human petrous bones, the optimal laser energy parameter for dissection of the posterior stapes crus and the footplate perforation were determined. With these parameters, stapedotomy was carried out with the Er:YAG laser in 29 patients with otosclerosis with a conventional dissection of the incudostapedial joint and the stapedius muscle tendon. The Er:YAG laser was used (60 or 100 mJ, 3-6 pulses) for dissection of the posterior stapes crus and footplate perforation. RESULTS: No intra- or postoperative complications were observed in all 29 patients. Vertigo and hearing loss were not observed intra- or postoperatively. The postoperative hearing results (improvement of the air-bone gap) was in all cases satisfactory (median remaining air bone gap, 8.1 dB). The median operation time was 29 minutes (15-42 minutes) and did not show a significant prolongation in comparison to the conventional technique. In 1 of the 29 patients, the footplate perforation needed to be carried out conventionally. CONCLUSION: For the first time, Er:YAG laser parameters have been optimized and refined in a human petrous bone model and were then used in a clinical setting. According to the presented results, the Er:YAG laser seemed to be a very suitable instrument for stapedotomy.
Adult↗
Transcriptional repression of the human fibronectin gene in laryngeal squamous cell carcinoma cells.
PURPOSE: The aim of the experiments was to analyze the mRNA expression pattern and verify the repression of FN gene expression in laryngeal squamous cell carcinoma (SCC) cells in comparison with benign mucosal keratinocytes. METHODS: Messenger RNA from SCC cells and benign keratinocytes was reverse transcribed and subjected to PCR following differential display (DD) analysis of the amplicons. Northern hybridization was carried out to confirm the reduction of the FN-mRNA expression in both laryngeal SCC cells and larynx carcinoma biopsies, in contrast to adjacent normal mucosa. Quantitation of protein synthesis was performed with homogenates of fresh tumor biopsies and their normal phenotypes, as well as of benign keratinocytes and laryngeal SCC cell lines, respectively, using ELISA. In the liposome-mediated transient transfection assay, FN promoter activity was analyzed by linking the FN promoter sequence to the chloramphenicol acetyltransferase (CAT) reporter gene. Transfection efficacy was monitored by co-transfection with pGL3 control vector. RESULTS: A 191 bp mRNA fragment revealing a 99% homology with the human FN-mRNA was detected, the expression of which was repressed 20 times as much in SCC cells as compared to benign phenotypes. Northern hybridization confirmed the distinctly reduced expression of FN-mRNA in both laryngeal SCC cells and larynx carcinoma biopsies, in contrast to adjacent normal mucosa. The quantitation experiments showed a correlation between the range of FN synthesis and the expression of FN-mRNA in cell lines and the biopsies which were used. The 1.28 kb FN gene promoter drove expression of the CAT reporter gene, which was similar to the FN-mRNA expression showed by DD and Northern hybridization. CONCLUSIONS: The mechanisms leading to the low level of FN in many tumors have not yet been sufficiently investigated. Our findings suggest that the decrease of FN in laryngeal SCC cells is transcriptionally regulated.
Base Sequence↗
Antibodies against oncoproteins E6 and E7 of human papillomavirus types 16 and 18 in patients with head-and-neck squamous-cell carcinoma.
Human papillomaviruses (HPVs) have been recognized as an essential pathogenic factor in anogenital cancer. HPV DNA has also been found in a subgroup of head-and-neck squamous-cell carcinomas (HNSCCs), and a causative role of the virus in the development of these tumors has been suggested by the concomitant inactivation of the tumor-suppressor protein pRb. Using 4 second-generation ELISAs, we found antibodies against at least 1 of the oncoproteins E6 and E7 of the high-risk HPV types 16 and 18 in 11 of 92 sera (12%) taken from HNSCC patients at or near diagnosis, in 1 of 52 sera (2%) taken from HNSCC patients >6 months after diagnosis and in 10 of 288 sera (3. 5%) taken from sex- and age-matched healthy control individuals of the normal population. In 11 of the 12 seropositive HNSCC cases, antibodies were directed against HPV16 proteins. In patients, the HPV16 antibodies were mostly of high titer, and in 6 cases, antibodies against both HPV16 oncoproteins were present. Seven of the 8 HPV16 antibody-positive sera from the control group were of low titer, and none of the 10 antibody-positive sera reacted with both oncoproteins of the same HPV type. The HPV type of the antigens detected by the antibodies in HNSCC patients correlated well with that of the HPV DNA found in the tumor. Of 19 patients known to have HPV16 DNA-positive tumors, 7 (37%) also had HPV16 E6 and/or E7 antibodies. Our finding suggests that the antibodies were formed in an immune response against HPV E6 and E7 proteins expressed in the HNSCC and thus strongly supports the concept of a biologically active role of HPV in the development of a subgroup of HNSCC.
Adult↗
[Analysis of the p53 gene status of lymph node metastasis in the head and neck region in occult primary cancer].
BACKGROUND: Lymph node metastasis in the head and neck region with occult primary cancer are a fairly rare tumor entity in head and neck cancer. Tumor biological parameters as well as mechanism and cause for the development of this so called "cancer of unknown primary" (CUP) are not well investigated in head and neck cancer. Mutations of the p53 tumor suppressor gene are the most prevalent genetic alteration of human malignancies and show an incidence of up to 50% in head and neck cancer. For a further tumor biological definition of CUP the p53 status was determined. METHODS: Twenty-three archival formalin fixed paraffined CUP of an occult squamous cell carcinoma of the head and neck region were examined. In all cases a primary cancer was never diagnosed. The DNA extracted from the tumor material was amplified with specific primers for exon 4-9 of the p53 gene and subsequently sequenced. RESULTS: None of the 23 CUP cases showed a mutation or polymorphism in exon 4-9 of the p53 gene. CONCLUSIONS: The total absence of p53 mutations in the so called mutational "hot spots" shows a significant difference to the frequency of primary tumors of the head and neck region. May be this tumor biological characterisation helps to further elucidate the growth behaviour of CUP in the head and neck region and the reason for their development.
Antisense Elements (Genetics)↗
Tracing human papillomavirus DNA in nasal polyps by polymerase chain reaction.
Human papillomavirus (HPV) infections are related to the genesis of various benign and malignant human neoplasias. The HPV types 16 and 18 seem to be causally related to the development of most squamous cell carcinoma of the anogenital tract and a proportion of carcinomas of the upper aerodigestive tract. The near 100% positivity of the HPV types 6 and 11 in laryngeal papillomatosis is well established. We investigated whether HPV also plays a role in non-neoplastic mucosal entities such as sinunasal polyposis, the genesis of which has been discussed as being triggered by viral infections. On DNA from 39 sinunasal polyps (33 patients), polymerase chain reaction (PCR) was performed using beta-globin primers for demonstration of amplifiable DNA in the tissue extracts. Consensus primers for the detection of several different HPV types were applied to the beta-globin-positive samples. The results were confirmed by Southern blot hybridization using consensus probes. Cycle sequencing was performed on the positive cases. All 39 samples showed positive signals for beta-globin. HPV-DNA investigations showed a slight positive signal in only 1 of the 39 investigated cases (2.6%). Further molecular investigations of this sample, including cycle sequencing, could not confirm this result. All the other tissue samples remained HPV-DNA-negative. Therefore, those HPV types readily detectable with the PCR primers and probes used are not frequently associated with sinunasal polyposis. The data confirm the hypothesis that HPV is correlated to a lesser extent to infectious mucosal lesions than to proliferative lesions. Furthermore, the results emphasize that the presence of HPV in specific lesions does not occur by chance, but represents a specific infection of the mucosa leading to proliferation and even to malignancy.
DNA, Viral↗
Serum p53 autoantibodies in the follow-up of head and neck cancer patients.
p53 autoantibodies (AAB) are a fairly new serological parameter in patients with malignancies. Although the actual mechanism of how they develop is still unclear, it seems that these AAB could be of prognostic relevance. Very few studies demonstrated the usefulness of p53 AAB in the follow-up of cancer patients. In this study, 109 patients with head and neck cancer were investigated using an ELISA for the presence of p53 AAB in their serum and were followed-up for at least 36 months. In 21 of the cancer patients, p53 serum AAB were detected. In 5/21 p53-seropositive AAB patients, a correlation with the clinical course was observed. Sixteen of the p53-positive patients did not show any significant AAB titer changes during the follow-up, and no significant correlation with the clinical course was seen. According to these results, the clinical value of p53 AAB in the follow-up of patients with head and neck cancer seems to be limited.
Adult↗
Transcriptional repression of the human galactocerebrosidase gene in squamous cell carcinomas of the larynx.
Alterations of gene expression in squamous cell carcinoma (SCC) cell lines derived from the larynx and keratinocytes derived from adjacent normal mucosa of the larynx have been studied using the mRNA differential display technique. Lane-to-lane comparison of reverse transcribed mRNA showed a strong repression of a 148 bp fragment in SCC cells. The fragment was reamplified and cloned. Sequencing revealed a 99.3% homology with a region in exon 17 of the human galactocerebrosidase (GALC) gene. Northern blot analysis confirmed the differential expression of this gene in both carcinoma cell lines and laryngeal SCC biopsies in contrast with corresponding normal mucosa. To provide further evidence for the differential expression rate, both types of cells were transiently transfected with a 152 bp (-176 to -24) high regulatory promoter element of the 5' flanking region of the GALC gene. Results of 3 independent transfection experiments indicated a 16-fold repression of the GALC gene expression in SCC cells compared with benign keratinocytes. However, neither mutation nor other alterations of the promoter sequence were detected. Expression of the GALC gene is thus greatly affected in SCCs of the larynx.
Base Sequence↗
[Re-amplification of differentially expressed mRNA fragments of head-neck cancers without cloning].
BACKGROUND: mRNA expression of healthy and malignant cells can be compared to each other by employing the "differential display" (DD) technique. Most studies describe sequence analysis of differentially expressed fragments after reamplification by a second round of PCR and subsequent molecular cloning to gain a sufficient amount of DNA for sequencing. The aim of this study was to show whether a sufficient amount of differentially expressed mRNA of squamous cell carcinoma cells of the head and neck region can be generated by PCR alone without cloning steps. MATERIAL AND METHODS: mRNA isolated from cultivated keratinocytes and squamous cell carcinoma cells was reverse transcribed into cDNA which was amplified with PCR. Differentially expressed fragments detected after gel electrophoresis were isolated from the gel and reamplified in a second PCR. The resulting cDNA amounts of the second PCR were suitable for cloning but not for direct sequencing. A third round of PCR with the undiluted final product of the second PCR as template regularly failed. Dilutions of the second PCR products between 1:10 and 1:10(10) were prepared. The third round of PCR was carried out with these various template concentrations. RESULTS: A sufficient amount of differentially expressed fragments for sequencing procedures resulted when dilutions of the second PCR products ranging from 1:10(2) to 1:10(7) were used as templates in the third round of PCR. CONCLUSION: Modifications of PCR parameters provide high DNA copy numbers of differentially expressed mRNA fragments from squamous cell carcinoma cells of the upper aerodigestive tract in amounts that are needed for sequence analysis. This may make it possible to avoid labor-intensive cloning procedures requiring high safety standards.
Base Sequence↗
Ultrasound-guided interstitial Nd: YAG laser treatment of voluminous hemangiomas and vascular malformations in 92 patients.
In many cases voluminous vascular anomalies of the head and neck region are still treated with conventional surgery, although neodymium:yttrium-aluminum-garnet (Nd:YAG) laser therapy offers a valuable treatment alternative. Ninety-two patients with voluminous hemangiomas and vascular malformations were treated with interstitial Nd:YAG laser therapy (power density, 1300 to 3300 W/cm2), partly complemented by a noncontact-mode Nd:YAG laser light application (energy density, 1000 to 2500 J/cm2). The vascular tumors had a diameter of more than 3 cm in at least two dimensions. Treatment was carried out under ultrasound and manual control. Nearly 60% of the patients (n = 55) showed a complete clinical regression. Thirty-three patients (35.8%) had a partial regression and were satisfied with the treatment outcome. Four patients were treated unsuccessfully with the laser, and three of them subsequently underwent conventional surgery. Only nine of the 92 patients (9.8%) showed cosmetic or functional impairments. The results of this first consecutive series study with a retrospective clinical evaluation of the interstitial Nd:YAG laser therapy of voluminous hemangiomas and vascular malformations in a large patient group demonstrate a high effectiveness of this novel therapy modality.
Adolescent↗
Differentially expressed genes in head and neck cancer.
Carcinogenesis is considered a multistep process. To further elucidate involved genetic changes, the differential display method was applied to compare gene expression of head and neck carcinoma cells and normal keratinocytes from the upper aerodigestive tract. Total RNA was extracted from cultured squamous carcinoma cells and keratinocytes. mRNA was reverse transcribed into cDNA, amplified by PCR, and separated on a gel. Currently three DNA transcripts were identified with a length of 191 to 336 base pairs (bp) that were either expressed only by the keratinocytes or by the malignant cells. Differentially expressed DNA fragments of the carcinoma cells and the keratinocytes were cloned and sequenced. A gene bank database search identified one fragment expressed by the carcinoma cells as an unknown gene, another one found in the keratinocytes as probably a part of the human cell attachment domain, and the third one with homology to the mRNA of the human epidermal growth factor receptor (EGFR). Northern blot analysis confirmed the differential expression in the malignant cells or the keratinocytes. Differential display seems to confirm the well-known overexpression and up-regulation of the EGFR, the differential expression of the cell attachment domain may play a role as a cofactor in carcinogenesis of head and neck cancer, and the third unknown fragment is still under investigation to elucidate the role in carcinogenesis.
Base Sequence↗
Recent advances. Otorhinolaryngology.
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Botulinum Toxins, Type A↗
Microendoscopic treatment of the hypopharyngeal diverticulum with the CO2 laser.
BACKGROUND AND OBJECTIVE: The hypopharyngeal (Zenker's) diverticulum is a herniation of mucosa and submucosa on the posterior wall of the pharynx. The only treatment is surgical. STUDY DESIGN/MATERIAL AND METHODS: Between 1976 and 1993, 109 patients with a hypopharyngeal diverticulum were operated on at the Department of Otorhinolaryngology, Head and Neck Surgery, University of Kiel, either transcutaneously combined with a cricopharyngeal myotomy (n = 76), or microendoscopically (n = 37) using the CO2 laser. Results and complications of both techniques were evaluated and compared. RESULTS: With both surgical procedures, > 90% of the patients were treated successfully. The rate of postoperative complications was generally low. In comparison to the microendoscopic procedure, serious complications were found to be more frequent in patients treated with the conventional transcutaneous diverticulectomy. CONCLUSION: The laser surgical tissue bridge dissection is a less invasive, quick, relatively safe, and effective procedure requiring only short hospitalisation. Therefore, the laser surgical tissue bridge dissection can be considered as the method of choice for the treatment of the hypopharyngeal diverticulum.
Adult↗
p53 serum antibodies as prognostic indicator in head and neck cancer.
p53 antibodies are a new serological parameter of unknown potential in patients with malignancies. Their occurrence has been described in various types of cancer patients. The mechanism underlying the immunization process is still unclear. We investigated the incidence of p53 serum antibodies in 143 head and neck cancer patients with an enzyme-linked immunosorbent assay. The posttherapy course of two matched study groups (n = 38 each), one p53-antibody-seropositive and one p53-antibody-seronegative, was followed up for 24 months. Thirty-nine head and neck cancer patients (27.3%) were seropositive for p53 antibodies. During the follow-up, the p53-antibody-seropositive patients accounted for more local tumor recurrences (n = 12 versus n = 8) and more tumor-related deaths (n = 11 versus n = 5) than did seronegative patients, and second primary tumors (n = 9 versus n = 0) occurred exclusively in seropositive patients. In total, therapy failures (recurrences, tumor-related deaths, second primaries) were observed in 17/38 cases (44.7%) in the p53-antibody-seropositive group and in 8/38 cases (21.1%) in the p53-antibody-seronegative group. These results, after a follow-up of 2 years, seem to indicate a prognostic value of p53 serum antibodies for therapy failure in patients with head and neck cancer.
Adult↗