Expression of matrix-metalloproteinases and their inhibitors in human cholesteatomas.

The proteolytic erosion of the temporal bone is the key event in the pathognomonic course of cholesteatoma progression. The molecular mechanisms of bone resorption, endangering the ossicles, the inner ear, the facial nerve, large vessels or the brain, are not understood. Recently, a new family of proteolytic enzymes, the matrix-metalloproteinases (MMP's) has been described and identified, which seems to play a pivotal role in matrix- and bone homeostasis and inflammatory osteolytic diseases, e.g. osteoarthritis and periodontitis. These enzymes are sophisticatedly controlled by specific inhibitors and activation cascades. We investigated whether human cholesteatoma tissue expresses MMP's and MMP-inhibitors. By immunocytochemistry of cholesteatoma-cryosections, the expression of MMP-2 (72 kD collagenase), MMP-9 (92 kD collagenase), and MMP-3 (stromelysin-1) could be seen to be strictly confined to the basal and suprabasal cell layer of the cholesteatoma epithelium. The neutrophil collagenase (MMP-8) showed a more disseminated expression in the epithelium and the granulation tissue as well. The tissue inhibitor of metalloproteases, TIMP-1, could be detected only in very limited areas of the granulation tissue in a quite randomized manner. Therefore, a derailment in favor of proteolysis of the normally tightly controlled MMP-system might be postulated. The results indicate that members of the MMP-family could play an active role in the molecular mechanisms of cholesteatoma invasion into the temporal bone. This offers new insights into the pathophysiology of the disease and of potential therapeutic approaches.

Mastoiditis and acute otitis media in children with cochlear implants: recommendations for medical management.

Acute otitis media (OM) or mastoiditis is a very dangerous condition for the ear after cochlear implantation. However, acute OM is very common in childhood and can occasionally occur in an implanted ear. Most cases of acute OM can be successfully treated with intravenous high-dosage antibiotics. In cases of mastoiditis and clinical signs of mastoid abscess, retroauricular drainage is necessary to prevent infection of the implant bed. In a series of 366 children given implants (1 to 14 years), acute OM occurred in 5.6% during a follow-up period of 1 to 8 years. Seven ears had to be opened by means of myringotomy. Five ears were opened by retroauricular incision with mastoid revision on the implanted side. Adenoidectomy and use of ventilation tubes before cochlear implantation, as well as careful subtotal mastoidectomy during the implantation, can reduce the incidence of acute OM in children after implantation. Early and subsequent treatment with operative mastoid drainage can prevent implant loss and should be performed at the implantation center.

Kochleaimplantat bei Erwachsenen: Indikation und Durchführung : Teil I: Diagnostik, Operationsverfahren und Ergebnisse.

From the technical point of view, cochlear implant (CI) surgery in adults is a well established procedure. Pre- and postoperative evaluation, surgical approach and rehabilitation programs are standardized, presenting CI as a low risk procedure with rare complications similar to those of middle ear surgery. Modern advanced CI devices offer technical reliability and multiple speech encoding strategies and recently, even small processors which are worn behind the ear. Further technical advances are continuously available, even for implanted patients. Upgrading is usually easy because the outer parts of the implant are exchangeable and software upgrades can be transmitted transcutaneously to the implant. Assuming that medical and rehabilitation requirements are available, there are only very few indications against CI in adults. Candidate patients should therefore be transferred to CI-centres where a decision can be taken depending on presurgical evaluation results.

Kochleaimplantat bei Erwachsenen: Indikation und Durchführung : Teil II: Spezielle Aspekte und Technik der Implantatsysteme.

From the technical point of view, cochlear implant (CI) surgery in adults is a well established procedure. Pre- and postoperative evaluation, surgical approach and rehabilitation programs are standardized, presenting CI as a low risk procedure with rare complications similar to those of middle ear surgery.Part 1 described the diagnostics, surgical procedures and possible complications. The second part will cover the contraindications, special cases as well as the technical parameters of the modern implantation system.

[Clinical picture and immunology of Wegener's granulomatosis]. / Clinique et immunologie de la granulomatose de Wegener.

In the last 21 years, 22 histologically proven cases of Wegener's granulomatosis (WG) were observed and treated. In 19 patients WG appeared primarily in the ENT-area. Ten patients had middle ear involvement. Whereas, in 9 cases the inner ear was affected too. Before introduction of immunosuppressive therapy the patients (n = 8) died averagely after 5.6 months after onset of the first symptoms. Under therapy with cyclophosphamide and prednisone total remission of WG can be reached for long times (n = 14, 3.2 years of follow up). In 14 cases serologically anti-cytoplasmatic antibodies against neutrophil granulocytes were determined in high activity stage of WG. In combination with the clinical and histological findings the determination of these antibodies gives the possibility to solve difficulties in differential diagnosis of WG.

Management of choanal atresia in cases of craniofacial malformation.

OBJECTIVE: To report the method and results of endonasal endoscopic approach in congenital choanal atresia in cases of craniofacial malformation. PATIENTS: The pathology of unilateral and bilateral choanal atresia and the treatment results in seven children treated between 1999 and 2006 are presented. 5 infants suffering from bilateral atresia also had severe malformations (Charge syndrome [2 patients], trisomy 18, microcephalus, central cranioschisis, cleft lip and anophthalmia 9). The surgical intervention was carried out immediately after birth. 2 patients with unilateral atresia were treated in their second and sixth year of life respectively. CT scan was the diagnostic procedure of choice. Intraoperative endoscopy showed both membraneous and osseous atresia. SURGICAL PROCEDURE: Trocars of different sizes were used to open the atresia plate, while the osseous parts were removed with diamond drills. Silicone tubes were inserted transnasally and remained in place for several months to improve the infants'ability to breath and drink. RESULTS: In all cases of bilateral atresia the tubes either had to be changed repeatedly or replaced with larger tubes due to dislocation and head growth. The septum was perforated in one case. No further stenoses were detected following the removal of the tubes (after 3-6 months). CONCLUSION: The transnasal access is particularly suited to newborns and infants because it induces a minor surgical trauma and carries a low risk of bleeding if endoscopes are used. The results show that the risk of restenoses can be minimised with sufficient fixating and in-patient care.

[Salivary duct carcinoma of the sublingual gland--a case report]. / Das Speichelgangkarzinom der Glandula Sublingualis.

RATIONALE: Pleomorphic adenoma is the most common neoplasm of major and minor salivary gland origin, followed by infectious reasons and sialolithiasis. Less common are adenocarcinomas presented. The salivary duct carcinoma represents a rare variant of the group of adenocarcinomas originated from the salivary glands, especially extremely rare from minor salivary gland origin. CASE REPORT: We report about a 52 year old male patient presenting with painless, non-ulcerating tumor at the floor of the mouth. Since 2 weeks ingestion was painful. Further ENT-investigations including endoscopy and scans (MRT, ultrasound) showed no pathology. In particular, growth of cervical lymph nodes and distant metastases were not revealed. A biopsy showed a rare salivary duct carcinoma of comedo-type originated from the left sublingual salivary gland. The patient underwent an operation: the tumor was extirpated in toto, and, as the pathohistological investigation confirmed, in sano. Additionally a neck dissection at the left side was performed, followed by the radiation of the tumor region and the lymphatic neck regions, after sufficient reconvalescence. The tumor-classification was pT3, pN0. Since 3 years no recurrence of the tumor was confirmed. DISCUSSION: Salivary duct carcinoma is a rare, high-grade malignant epithelial neoplasm, which occurs almost exclusively in the parotid. As presented, it can also occur in minor salivary glands. Histologically it is composed of structures that resemble expanded salivary glands. Comedonecrosis of these structures is a frequent feature. There is some histologic similarity to intraductal carcinoma of the breast. Differential diagnosis comprises adenoid cystic carcinoma, metastases of other adenocarcinomas, such as the carcinoma of the thyroid gland and the comedocarcinoma of the breast. Because of its poor prognosis a rapid and radical therapy is recommended. CONCLUSION: A rare case of a salivary duct carcinoma of sublingual salivary gland origin is presented. Usually the prognosis is poor. The adequate therapy is the complete surgical extirpation including the surgery of the regional lymphatic nodes and the additional radiotherapy.

[Choristoma in the vocal fold]. / Choristom des Taschenbandes.

Choristoma in the larynx is rare and related to thyroid or glial tissue. The manifestation of salivary gland tissue in the larynx has not been reported to date. We present the case of an 80 year old male complaining of hoarseness and productive coughing. A left side tumourous swelling was seen in the larynx with intact vocal cord mobility. Using microlaryngoscopy the mass was resected without any intra- or postoperative problems. Histologically, a choristoma-heterotopic salivary gland tissue in the muscle and fat tissue--was found. The mucosa was intact and there were no signs of malignancy. Differential diagnosis of such masses in the larynx include benign lesions as well as specific infections, e.g. tuberculosis, sarcoidosis, amyloidosis and Wegener's granulomatosis. Especially in non-smokers, sarcoma, lymphoma and melanoma should be separated from the frequent squamous cell carcinoma of the laryngeal tissue. In rare cases, heterotopic tissue can mimic a tumourous mass. Intralaryngeal resection is the therapy of choice and should be recommended to the patient.

[The interesting case -- case no. 70]. / Der interessante Fall Nr. 70.

We will report two cases of newborn girls, who could not be breast fed because of a benign tumour in their oral cavity. These polypoid lesions were located in both cases in the labial aspect of the dental ridge. Tumours were fleshy, firm, dark-brown with a broad-based attachment to the alveolar ridge. The underlying bone was not affected. The size of neoplasm was in one case 3 x 2 cm, in the other one 2 x 1.5 cm. Excision was performed in both cases at the day after birth. The postoperative course was uncomplicated. A regular oral feeding was immediately possible. Histological findings showed large tumour cells with abundant granular eosinophilic cytoplasm and a prominent vascularity. Cells did not show immunostaining for laminin or S-100 protein. All these findings are characteristic of congenital granular cell tumour and its synonym congenital epulis. There is a strong predilection for newborn females. It differs from adult granular cell tumours by its prominent vascularity, the presence of scattered remnants of odontogenic epithelium, and the strong phosphatase activity. These lesions are always cured by local excision. The exact nature of this condition is still not clear, and there is little support for its originating from odontogenic epithelial cells.

[Granular cell tumor -- a rare tumor lesion of submandibular gland origin]. / Granularzelltumor, ein seltener Tumor der Glandula submandibularis.

RATIONALE: Granular cell tumors are rare entities with manifestations in nearly all organ systems. Appearance in salivary glands is observed in singular cases. CASE REPORT: We report a 54 years old female patient with a painless submandibular tumor lesion. Using a submandibular approach the tumor was totally removed with the submandibular gland. Histologically a benign granular cell tumor was diagnosed. The immunohistological examination revealed positive for S-100 antigen and vimentin, negative for KL1 antigen. The clinical follow-up for about 3 years was without complications or tumor recidive. CONCLUSIONS: A differential diagnosis of a submandibular mass is the rare manifestation of a benign granular cell tumor. The neurogen origin can be proven immunohistologically by positive S-100 antigen detection. The complete surgical resection is the therapy of choice.

[Malignant transformation of a juvenile papilloma in a 11 year old boy]. / Maligne Entartung einer juvenilen Kehlkopfpapillomatose bei einem 11-jährigen Jungen.

BACKGROUND: The juvenile laryngeal papilloma is the most common benign neoplasm in children. Often the entity shows an elongated recurrent course of disease with an expansion into the tracheo-bronchial system. Sporadic malignant transformation in adults with a papilloma was reported after treatment with radiotherapy alone or in combination with the intake of additional toxins (e. g. nicotine). Similar reports of a malignant transformation of juvenile papillomas without additional risk factors is very rarely reported. CASE REPORT: We report about an 11 year old boy, who suffered from a juvenile laryngeal papilloma. The multiple laser surgical procedures and a therapy with interferon resulted in a short-term remissions. A tracheotomy was inevitable. Seven months after the first diagnosis of the papilloma a regional metastatic squamous cell carcinoma was found. In spite of combined radiotherapy and chemotherapy the boy died 11 months later. CONCLUSIONS: The spontaneous malignant transformation of a juvenile papilloma in a squamous cell carcinoma is extremely rare. The surgical intervention as well the radiotherapy and chemotherapy using interferon was unsuccessful due to the high grade of malignancy. In view of the very short time interval between first diagnosis of juvenile papilloma and the subsequent malignant transformation, one must consider either the potential presence of a very aggressive form of papilloma or alternative two coincident independent diseases.

[Laryngeal tuberculosis today. A case report]. / Die Kehlkopftuberkulose heute. Ein Fallbericht.

We report the clinical, CT and histopathological findings of an 84-year-old female with laryngeal tuberculosis. Despite extensive clinical investigations no other manifestation of tuberculosis was found. Antituberculous therapy healed the disease. The clinical relevance and the differential diagnosis of laryngeal tuberculosis are discussed.

[Non-Hodgkin's lymphoma of the parotid gland]. / Non-Hodgkin-Lymphome der Ohrspeicheldrüse.

Since 1969 we have seen 17 patients with non-Hodgkin's lymphoma of the parotid gland. Retrospective analysis of these patients reveals that the primary diagnosis was established in 14 patients by parotid surgery. In 10 (58.8%) cases there was a single focus of NHL in the parotid gland proven by extensive medical and radiological examinations. Histology showed that 14 (82.3%) of the tumors were low grade and 3 (17.7%) were high grade (Kiel classification). In 5 specimens myoepithelial sialadenitis was found in the parotid gland tissue. Six patients died within 1.5 years on average, 4 of them without evidence of disease. Four of the 7 patients alive have been followed for an average of 3.1 years without evidence of disease. Primary radiation of the parotid region in stage IE in cases of parotid gland NHL seems to be an effective therapy. NHL presenting in myoepithelial sialadenitis seems to be rare, but offers the opportunity of observing an organ specific malignant process.

Ear involvement in Wegener's granulomatosis.

In 16 of 19 patients with biopsy-proved Wegener's granulomatosis the early manifestations were limited to the ear and nose. The audiological data of 13 patients revealed middle ear involvement in 16 of 26 ears. Twenty-one of 26 ears presented with a low to moderate sensorineural hearing loss. One ear remained deaf after a sudden hearing loss in the early stage of the disease. Serologically, 4 of 6 tested patients with sensorineural hearing loss demonstrated antibodies against sarcolemma. One patient showed antinuclear antibodies. It is remarkable that these antibodies can often be detected in classic inner ear disorders. The course of inner ear function, serum findings and the success of immunosuppressive therapy in Wegener's granulomatosis are comparable with immunologically mediated vasculitis in the inner ear.

[Perspectives of molecular genetics of hearing disorders]. / Perspektiven der Molekulargenetik von Hörstörungen.

In the last few years research efforts have succeeded in detectury the genetic background of several hereditary hearing disorders by molecular biological methods. The genetic code was been decoded for Neurofibromatosis types 1 and 2, as well as for such X-linked diseases as Alport's syndrome or Norrie's disease. Besides the classic genetic tools as chromosomal analysis, molecular biological techniques and methods have become important clinically for the ENT-specialist. In the present review we show the principles and applications of DNA-and RNA-analysis with hybridization techniques in Southern- and Northern-blot techniques, as well as in-situ hybridization and polymerase chain reaction (PCR). These molecular biological techniques will help improve the detection and analysis of hereditary inner ear disorders, but also be able to study in greater detail tumor carcinogenesis and mutagenesis. The various techniques are explained and the applications are demonstrated.

[Closure of septum perforation using an individual obturator]. / Septumperforationsverschluss durch einen individuellen Obturator.

Alternatively to operative procedures we present the production of an individually formed septal obturator to close an iatrogenic septal perforation. After taking the impression from the perforation the obturator was casted out of silicone via a plaster mould. This possibility can help in those cases where septal perforation cannot be closed by operative procedures.

[Histology and morphometry of explanted ear ossicles in man]. / Zur Histologie und Morphometrie explantierter Gehörknöchelchen beim Menschen.

Reoperations of the middle ear enable histological and morphometrical examination of explanted autogenetic or allogenetic ossicles. Histological and morphometric study of such ossicles showed a different osteogenesis. In autogenetic ossicles, angiogenetic and appositional osteogenesis could be seen; in allogenetic ones, angiogenesis was predominant. Connective tissue prevailed in allogenetic ossicles. The histological findings were in accordance with morphometric results and with statements from literature.

[Extra-temporal localized facial neuromas]. / Uber extratemporal lokalisierte Facialisneurinome.

Nine facial nerve schwannomas were observed in more than 1,350 operations on the parotid gland. Eight patients had a pre-operative diagnosis of pleomorphic adenoma without facial palsy. One patient who underwent extensive surgery without preservation of the facial nerve for a tumour present for more than 10 years had a pre-operative facial palsy. Facial nerve function recovered totally or partially in six peripheral schwannomas. In two cases with main trunk schwannoma no reinnervation was observed despite end-to-end anastomosis or interposition of the great auricular nerve. Histology showed eight typical schwannomas and one neurofibroma. Neurofibromas are extremely rare in the parotid gland. Clinical and operative experience with parotid gland schwannomas shows that recovery of facial nerve defects is mostly incomplete. Reconstructive methods should be used, but the long-term prognosis is uncertain.

[Immunologic findings and therapeutic results in chronic progressive inner ear hearing loss]. / Immunologische Befunde und Therapieergebnisse bei chronisch-progredienter Innenohrschwerhörigkeit.

In a retrospective study of 147 patients with progressive sensorineural hearing loss we analysed the therapeutic results in relationship to the serum tissue antibody. Serum antibodies against heterologous tissue were detected in about 50% of the patients studied. These antibodies were mainly against sarcolemma, endothelium and smooth muscle. One group of patients was treated with corticosteroids. In this group, one third of the antibody-positive patients and 10% of the antibody-negative patients had hearing improvement. The second group of patients was treated with rheological substances (Dextrane 40 with Procaine or Naftidrofuryl). In this group, there was hearing improvement in 17% of the antibody-positive and 20% of the antibody-negative patients. The results of our study suggest that routine immunological tests may not be sufficient to predict the usefulness of corticosteroid treatment. It may be necessary to develope new immunological techniques which are more specific to the inner ear.

[Intratemporal facial neurinoma]. / Das intratemporale Fazialisneurinom.

Two patients with intratemporally localised facial nerve schwannomas developed conductive hearing loss beside persisting facial nerve palsy. Tympanotomy revealed a tumour of the facial nerve that was totally removed. In one case reconstruction was performed with great auricular nerve interposition. The long-term follow-up (12 years) showed a good functional result. Facial nerve schwannomas present problems in detection, and reconstruction methods are not safe with regard to long-term prognosis.