Comparative miRNA Expression Profile Analysis of Squamous Cell Carcinoma and Peritumoral Mucosa from the Meso- and Hypopharynx.

BACKGROUND/AIM: The role of microRNAs (miRNA) in carcinogenesis is related to their genome-regulatory function. The aim of the present study was to identify and compare miRNA expression signatures of meso- and hypopharynx squamous cell cancers in consideration of the cancer field hypothesis. PATIENTS AND METHODS: Thirteen snap-frozen biopsy series of tumors and peritumoral tissues from the meso- and hypopharynx were analyzed regarding their miRNA expression with quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Significant miRNA expression changes of miR-21, -27a, -34a, -143 and -146a were found in peritumoral tissues that were dependent from the tumor location and the distance from the primary tumor site. CONCLUSION: miRNA expression analysis was found to be appropriate for molecular segregation of tumor location and peritumoral tissue segments, and appears to be a promising marker for cancer field characterization.

Retrospective analysis of tympanoplasty in children with cleft palate: a 24-year experience. II. Cholesteatomatous cases.

BACKGROUND: Contradictory experience has been published on the outcomes of ear surgery in patients with cleft palate. OBJECTIVES: The authors of this study investigated whether there were differences in the short- and long-term outcomes of tympanoplasty performed due to cholesteatoma in children with or without cleft palate. SETTING: Tertiary care medical centre. METHODS: The authors retrospectively analyzed the first author's 24-year experience of paediatric tympanoplasty using the software programme developed by the fourth author. The outcomes of 268 tympanoplasties on 172 ears with cholesteatoma in 151 'NoCleft' patients were compared to the outcomes of 35 tympanoplasties on 20 ears of 19 'Cleft' patients. The average age of the patients was 10.7±3.6 years and 9.5±2.7 years respectively. The average follow-up time was 4 and 4.1 years. RESULTS: Preoperative PTA-ABGs (31.22/34.88 dB; p=0.058), best postoperative PTA-ABGs (17.04/16.4 dB; p=0.499), last postoperative PTA-ABGs (19.93/20.98 dB; p=0.298), the final hearing improvement (11.29/13.9 dB; p=0.193) and postoperative PTA-ABG deterioration with time (2.89/4.58 dB; p=0.117) were statistically compared between the 'NoCleft' and 'Cleft' groups. The same parameters were analyzed separately in the case of tympanoplasty performed with intact ossicular chain and the different type of columella ossiculoplasty. No significant differences were found between the two groups in any of these parameters. However, significant difference was found in the necessity for grommet insertion (8-fold difference, p≈0), and conversion to open techniques (p≈0). CONCLUSIONS: The authors conclude that the achievable audiological outcomes of tympanoplasty in children with cleft palate and cholesteatoma do not differ significantly from those of the general child population. However, this more frequently requires ventilation tube insertion and more frequent follow-up visits. The latter is ensured by patient care within the frameworks of the 'Cleft Palate Team'. We have to accept that in some cases Eustachian tube dysfunction caused by the underlying disease (cleft palate) 'takes over' and we have to resort to open techniques.

[MicroRNA expression profiles in squamous cell carcinomas of the meso- and hypopharynx]. / Mikro-RNS-expressziós mintázatok mesopharynx-hypopharynx laphámcarcinomákban.

INTRODUCTION: MicroRNAs play a role in carcinogenesis through their genome regulatory function. AIM: The aim of the authors was to identify and compare microRNA expression signatures of meso- and hypopharynx squamous cell cancers on the basis of the cancer field hypothesis. METHOD: Using standard mapping biopsy (tumour tissue and macroscopically normal tissues obtained 1, 2 and 3 cm from margin) 13 snap frozen sample series were analysed for microRNA expression with quantitative real-time polymerase chain reaction. RESULTS: MiR-221 was significantly overexpressed in mesopharynx cancers, whole miR-21, miR-143 and miR-155 showed significant overexpression in hypopharynx cancers. CONCLUSIONS: Using microRNA expression profiles the authors were able to distinguish peritumoural tissues according to distance from the primary tumour site. Future application of the method may prove to be useful in early detection of the altered epigenetic regulation in tissue fields representing normal phenotype. This may be helpful in cancer risk assessment and prevention.

Retrospective analysis of tympanoplasty in children with cleft palate: a 22-year experience: I. Mesotympanic (non-cholesteatomatous) cases.

BACKGROUND: Contradictory data have been published on the outcomes of ear surgeries in cleft patients. OBJECTIVES: To investigate whether there are differences in the short and long term outcomes of tympanoplasty performed due to childhood chronic mesotympanic otitis media in patients without and with cleft palate. SETTING: Tertiary care pediatric medical centre. METHODS: The authors retrospectively analysed the first author's data on pediatric tympanoplasties of the past 22 years with the help of a computer programme developed by the third author. The outcomes of 159 'NoCleft' tympanoplasties (119 patients, 144 ears) were compared to the outcomes of 31 'Cleft' tympanoplasties (21 patients, 27 ears) with the average age of the patients being 10.8 and 10.7 years accordingly. RESULTS: The preoperative ABG (28.76/28.94dB, p = 0.468), the best postoperative ABG (12.78/10.04dB, p = 0.096), the last postoperative ABG (15.59/13.19dB, p = 0.192), the final hearing gain (13.17/15.75dB, p = 0.253) and the postoperative ABG deterioration associated with time (2.81/3.15dB, p = 0.376) were statistically compared in the 'NoCleft'/'Cleft' groups. No significant difference was found between the outcomes of the two groups. The same parameters were examined separately after tympanoplasties performed with intact ossicular chain and after those requiring columella ossiculoplasty. The 'Cleft' group did not have worse outcomes in this respect, either. The average follow-up period of the patients was more than 3 years in both groups. The graft take rate was 100%, reperforation occurred in 3.5% of the cases in both groups. In their study, grommet insertion was more likely to be necessary in the 'Cleft' group. CONCLUSION: The authors concluded that there was no significant difference between the expectable outcomes of pediatric tympanoplasties in patients with and without cleft palate regarding mesotympanic cases; therefore, the indications for tympanoplasty are the same in the two groups. They outline the importance of the therapeutic management of cleft patients in the frameworks of a "Cleft Palate Team" and the necessity for their lifelong otorhinolaryngological care due to their vulnerable Eustachian tube function. They are planning to publish the same comparative analysis of their patients with cholesteatoma in a following study.

Sedation of children for auditory brainstem response using ketamine-midazolam-atropine combination - a retrospective analysis.

Authors investigated sedation quality in children for auditory brainstem response testing. Two-hundred and seventy-six sedation procedures were retrospectively analyzed using recorded data focusing on efficacy of sedation and complications. Intramuscular ketamine-midazolam-atropine combination was administered on sedation preceded by narcotic suppository as pre-medication. On using the combination vital parameters remained within normal range, the complication rate was minimal. Pulse rate, arterial blood pressure and pulse oxymetry readings were stable, hypoventilation developed in 4, apnoea in none of the cases, post-sedation agitation occurred in 3 and nausea and/or vomiting in 2 cases. Repeated administration of narcotic agent was necessary in a single case only. Our practice is suitable for the sedation assisting hearing examinations in children. It has no influence on the auditory brainstem testing, the conditions necessary for the test can be met entirely with minimal side-effects. Our practice provides a more lasting sedation time in children during the examination hence there is no need for the repetition of the narcotics.

Long-term results of the use of autogenous cortical bone columellas to replace the stapes at stapedectomy.

The first author has been using an autogenous cortical bone columella to replace the stapes removed during stapedectomy since 1965. The audiograms of 21 of the 271 patients operated on with this method between 1965 and 1989 (i.e. 7.7% of the possible candidates) were available 20-35 (average 26.8) years postoperatively. The operation could be regarded as successful in 20 and unsuccessful in 1 patient in the long run. The audiological data are presented individually as averages of the values obtained at 0.5, 1, 2 and 3 kHz. The averaged data (n = 21): preoperative air conduction, 58.27; bone conduction, 24.46; and air-bone gap, 33.81 dB. Postoperative best air conduction, 19.07; bone conduction, 14.10; and air-bone gap, 4.97 dB. Postoperative recent air conduction, 45.77; bone conduction, 38.45; and air-bone gap, 7.32 dB. The best values were measured 1-8 (average 1.57) years postoperatively. In relation to the postoperative best value, the recent value of the air-bone gap had deteriorated by 2.35 dB, and that of the bone conduction by 24.35 dB. The small air-bone gap indicates that the deterioration of the hearing is mainly caused by the deterioration of the function of the inner ear and not by that of the conductive apparatus. The progression of the deterioration differs individually (0.3-1.6, average 0.93 dB/year) and accelerates with age. This finding seems to be a problem that does not depend on the operative technique. The data show that the autogenous bone columella ensures the same good and lasting results as the alloplastic solutions; moreover, there is no problem with the incus-prosthesis connection.

Otosclerosis: disturbed balance between cell survival and apoptosis.

HYPOTHESIS: Otosclerosis is an inflammatory bone remodeling disorder of the human otic capsule, which might be characterized by a disturbed balance between cell survival and apoptosis due to an increased expression of inflammatory cytokines, mainly tumor necrosis factor-[alpha] (TNF-[alpha]). BACKGROUND: Histologic features of otosclerosis have been well described; however, different histopathologic and clinical stages have not been attributed precisely to the molecular biology of the pathologically increased metabolism of bone-forming and bone-resorbing cells. METHODS: Forty ankylotic stapes footplates (n = 40, males = 17, females = 23) removed by stapedectomy were histologically analyzed by conventional hematoxylin-eosin staining, and hCIAP1/2 (inhibitors of apoptosis) and granzyme-[beta] (apoptosis inducer) specific immunofluorescent assays were performed. Four normal stapes footplates obtained from cadavers with negative otologic history were used as negative controls. RESULTS: Active otosclerosis (n = 19) was featured by robust expression of apoptosis inhibitor proteins hCIAP1/2 and negligible expression of granzyme-[beta]. Inactive cases of otosclerosis (n = 8) were characterized by inverse reaction: granzyme-[beta] was highly expressed; however, hCIAP1/2 specific immunoreactions were absent. Nonotosclerotic and normal stapes specimens showed no considerable little granzyme-[beta] expression and moderate hCIAP1/2-specific immunoreactions. Expression pattern of apoptosis-associated proteins showed strong correlation with the histologic diagnosis and activity of otosclerosis (Yates-corrected [chi]2 test, p < 0.001). CONCLUSION: Detection of the inversely expressed apoptosis inhibitor and inducer proteins in active and inactive stages of otosclerosis demonstrates pathologic regulation of cell survival and apoptosis. These results may suggest active otosclerosis inactivation by TNF-[alpha] induced apoptosis. Anti-TNF-[alpha] biologics may serve as an option in the medical treatment of active otosclerosis.

Prospective effectiveness of stapes surgery for otosclerosis in a multicenter audit setting: feasibility of the Common Otology Database as a benchmark database.

INTRODUCTION: The Common Otology Database (COD) is a joint effort by an international group of otologists to organize audit with a standardized reporting method in middle ear surgery. The first results on hearing outcome of the COD are presented in this article. OBJECTIVE: The primary objective was to confirm the validity of the benchmark group by comparing hearing outcome results with previously reported results. The secondary objective was to describe the population, technical aspects, and hearing outcomes of stapes surgery. STUDY DESIGN: Nonrandomized prospective multicenter audit. SETTING: Twenty tertiary-referral otologic centers. PATIENTS AND INTERVENTION: Primary and revision stapes operations in patients with otosclerosis. MAIN OUTCOME MEASURES: Air-bone gap (ABG), bone-conduction (BC) thresholds, and air-conduction (AC) thresholds were evaluated at 3 and 12 months according to the guidelines of the Committee on Hearing and Equilibrium for the evaluation of conductive hearing loss. Raw data were displayed in an Amsterdam Hearing Evaluation Plot. RESULTS: In primary stapes surgeries, the postoperative ABG was closed to 10 dB or less in 63.6% and to 20 dB or less in 92.6% (median, 8.75 dB). In revision stapes surgeries, the postoperative ABG was closed to 10 dB in 41.2% and to 20 dB in 76.5% of cases (median, 11.25 dB). The overall mean postoperative ABG at 12 months was 10.38 dB compared with 28.75 dB preoperatively. Using laser to perform the fenestration results in a less pronounced BC improvement when compared with procedures without laser assistance. No statistically significant difference in ABG pure-tone average at 3 months could be demonstrated between the different prosthesis types. CONCLUSION: Results of hearing outcome are similar to previous, primarily retrospective, single-center studies. Our data confirm the effectiveness of stapes surgery in patients with otosclerosis.

Histopathology of nonotosclerotic stapes fixations.

HYPOTHESIS: Different diseases without exact histopathologic classification can cause stapes ankylosis. BACKGROUND: Otosclerosis is a complex bone remodeling disorder of the otic capsule due to persisting measles virus infection and consecutive inflammatory reaction. In fact, clinical and demographic features of otosclerosis have reference to stapes ankylosis. In the clinical practice, otosclerosis and stapes ankylosis are incorrect synonyms. METHODS: Nonotosclerotic stapes footplates (n = 284) removed during stapedectomy were analyzed histologically. Otosclerosis was excluded during the histologic preselection (n = 437). Total RNA was extracted, and measles virus-specific reverse-transcriptase-polymerase chain reaction was performed. RESULTS: Nonotosclerotic stapes ankylosis was associated with total absence of measles virus RNA. Six main types of nonotosclerotic stapes fixations could be distinguished histologically: annular calcification (n = 152; 53.5%), globular fibrosis (n = 49; 17.25%), lymphocytic infiltration (n = 31; 10.9%), hemosiderosis (n = 22; 7.75%), granulomas (n = 17; 6%) and amyloidosis (n = 13; 4.6%). Fragmentation of nonotosclerotic stapes footplates was infrequent (7%) during stapes surgery. Only 1 floating footplate (0.35%) was reported. CONCLUSION: Two thirds of nonotosclerotic stapes footplates represented complete pathologic bone remodeling. Unlike otosclerosis, nonotosclerotic stapes fixations were characterized by basic histopathologic findings without organ specificity that can also be identified in case of different diseases. Prevalence of nonotosclerotic stapes ankylosis is approximately 30 to 40% among stapes fixation cases. The long-term prognosis and surgical considerations theoretically differ from those of otosclerosis.

Necrosis of the long process of the incus following stapes surgery: new anatomical observations.

OBJECTIVES/HYPOTHESIS: The most frequent complication (generally recognized during revision procedures) following seemingly successful stapedotomies and stapedectomies is necrosis of the long process of the incus. This is currently ascribed to a malcrimped stapes prosthesis or to a compromised blood supply of the incus. The two-point fixation can cause a mucosal injury with a resulting toxic reaction, and also osteoclastic activity. An important aspect in the engineering of ideal stapes prostheses is that they should be fixed circularly to the long process of the incus with appropriate strength. The objective of this study was to compare current knowledge relating to the blood supply of the ossicular chain with the present authors' observations on cadaver incudes. Most of the papers dealing with this issue appeared in the mid-20th century. METHODS: The published data were compared with the authors' findings gained from photodocumentation on 100 cadaver incudes. The photos were taken with a Canon EOS 20 digital camera (Canon, Inc., Lake Success, NY) with a 5:1 macro-objective. The long processes of the incudes were examined from four directions under a Leica surface-analyzing microscope (Leica Microsystems GmbH, Wetzlar, Germany). RESULTS: Analysis of the positions of the entrances of the feeding arteries (nutritive foramina) on the incudes revealed 1-4 nutritive foramina on the long processes of 48% (24) of the left-sided incudes and 56% (28) of the right-sided incudes. The positions of these foramina differed, however, from those previously described in the literature. They were mostly located not on the medial side of the incus body or on the short process or on the cranial third of the long processes, but antero-medially, mostly on the middle or cranial third. In 48% of all the incudes examined, an obvious foramen was not observed either in the body or in the long process of the incus. No relationship was discerned between the chronological age of the incus specimens and the numbers and/or locations of the nutritive foramina. In each case, the opening of the foramen was the beginning of a tunnel running obliquely and medially upward through the corticalis of the long process of the incus. The foramina are thought to be capable of ensuring a richer blood supply between the surface and the inside of the long process, allowing the arteries to run in and out. CONCLUSIONS: These observations indicate that conclusions drawn from classical anatomical works appear to need reconsideration. The present authors consider that the reason for the necrosis of the long process of the incus is not a compromised blood supply, except in some exceptional anatomical situations. They discuss the possible reasons why malcrimping may lead to necrosis of the long process of the incus. To prevent such malcrimping, attention is paid to the new generation of prostheses.

[Postoperative application of amphotericin B nasal spray in chronic rhinosinusitis with nasal polyposis. Can recidive polyposis be prevented?]. / Amphotericin B-tartalmú orrspray posztoperatív alkalmazása orrpolyposissal járó krónikus rhinosinusitis eseteiben. Megelozheto-e a recidíva?

UNLABELLED: Chronic rhinosinusitis affects 1-4% of the adult population. The aetiology of this multifactorial, chronic disease, which leads to a significant impairment of the quality of life, often accompanied by nasal polyposis, is not fully understood. In the past decade it was presumed that the disease, which causes characteristic eosinophilic infiltration of the nasal mucosa, is triggered by an enhanced (but not classical allergic IgE type) immune response. AIM: If this supposition is correct, then it appears obvious that the administration of amphotericin B nasal spray in adequate concentration following endoscopic polypectomy should be advantageous for these patients, and might even reduce the number of recurrent cases. METHODS: To check on this assumption, the authors conducted a prospective randomized placebo-controlled trial involving 33 patients, 30 of whom remained in the study throughout. Patients with nasal polyposis were operated on with an endoscopic technique between 1 November 2005 and 1 October 2006; one group of them (group A, 14 randomly selected patients) was treated with a nasal spray containing 5 mg/ml amphotericin B, while the placebo group (group B, 16 randomly selected patients) received a nasal spray lacking amphotericin B. The results were evaluated with the aid of a modified Lund-Mackay CT score, the SNAQ-11 test (which evaluates changes in the symptoms), the life-quality test and endoscopy. The SPSS 14.0 for Windows program was utilized to process the data of examinations performed preoperatively and one year postoperatively. RESULTS: The CT scores of the group A patients exhibited wide scattering without signs of recovery one year after the operation. The CT scores of the group B patients indicated a slight improvement, though this did not prove significant in relation to group A. Both the SNAQ-11 test and the life-quality test revealed a significant improvement in each group, but the degrees of change in these tests did not significantly differ between the two groups of patients. The endoscopic findings indicated a slight improvement to the advantage of the amphotericin B-treated group 12 months after the operation. CONCLUSION: These results lead to the conclusion that the administration of amphotericin B nasal spray to patients operated on for nasal polyposis does not give rise to a significant alteration in CT scores, clinical symptoms, or quality of life. The more favourable clinical aspects observed in the amphotericin B-treated group during the endoscopic follow-up did not correspond to an improvement in the symptoms. In connection with the conclusions drawn from this study the authors discuss the available data on the fungal theory. They critically analyse the contradictory observations of 7 recent clinical studies.

Investigation of the effects of PACAP on the composition of tear and endolymph proteins.

Pituitary adenylate cyclase activating polypeptide (PACAP) is widely distributed in ocular tissues, including the lacrimal gland. PACAP has been shown to influence the activity of several exocrine glands, but its effects on the composition of the tear film are not known yet. Similarly, the presence of PACAP has already been shown in the inner ear, but it is not known whether PACAP influences the composition of the endolymph. The aim of the present study was to investigate whether systemic injection of PACAP has any modulatory effects on the protein composition of the tear film and endolymph using chip electrophoresis and mass spectrometry analysis. Tear and endolymph samples were collected from rats and chickens, respectively, at various time points after systemic injection of PACAP. Fluid samples were further processed for chip electrophoretic studies. No difference was found in the protein composition of the endolymph between control and PACAP-treated animals. In contrast, tear samples showed a marked difference after PACAP treatment. Proteins in the molecular range 50-70 kDa, which showed a different chip electropherogram profile in every PACAP-treated sample, were further analyzed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. PACAP treatment induced a repression in certain keratins, while others were induced after PACAP injection. Furthermore, PACAP treatment decreased aldehyde dehydrogenase expression. The present study provides a base for further studies on the in vivo effects of PACAP on the composition of tear film. These investigations may have important clinical relevance because of the noninvasive sample collection, the correlation between tear proteins and ocular diseases, and the possible presence of biomarkers for both ophthalmological and systemic pathological conditions.

[Frequency of coagulopathies in cases with post-tonsillectomy bleeding]. / Coagulopathiák gyakoriságának vizsgálata tonsillectomiákat követo utóvérzések eseteiben.

INTRODUCTION: The most serious complication of tonsillectomy is haemorrhage. Primary post-tonsillectomy bleeding occurs during the first 24 hours following the procedure as a consequence of inadequate suturing/ligation of the feeding arteries. Secondary post-tonsillectomy bleeding occurs most frequently between the 5-8. postoperative days. The role of different risk factors has intensively been examined in the background of secondary post-tonsillectomy bleedings, however, their real role is rather confusing. AIM: The aim of the present study was to examine whether preoperative haematological screening in order to detect hidden coagulopathies in the background of post-tonsillectomy bleedings is reasonable or not. METHOD: Of the 115 patients who were admitted to the Department of Otorhinolaryngology, Head and Neck Surgery, Medical School, University of Pécs, between 2002 and 2004, 107 patients (59 female, 48 male, average age 29+/-10.9 years) were asked to undergo screening of the following factors: thrombocytes, bleeding time using the Ivy method, thrombin time, activated partial prothrombin time, prothrombin/INR ratio, fibrinogen level. RESULTS: Of the 58 patients who accepted the invitation 28 (49%) presented with abnormal screening results. Isolated factor determination was recommended to all of them, however, only 19 patients (68%) turned up for the second screening. In 2 cases--3.4% of the re-examined patients--unknown coagulopathy was diagnosed: isolated factor VII underproduction in 1 patient and combined factor VII and XII underproduction also in 1 patient. Three female patients presented with a surprising isolated factor IX overproduction which proned them to thrombosis: all 3 patients had been on oral anticoncipients. CONCLUSIONS: From this study several conclusions can be drown for the practising physician: 1. the universal preoperative haematological screening does not seem to be cost-effective; 2. in cases of children, especially if the family history and also both the preoperative history and detailed physical examination are suspicious (e.g. recurrent mild nasal bleedings!) hidden coagulopathy needs to be ruled out; 3. in our study activated partial thromboplastin time seemed to be the most sensitive screening parameter; 4. due to the fact that coagulopathies are inherited diseases, the diagnosis of a patient with a particular hidden coagulopathy can contribute to the exploration of further family members; 5. the vast majority of secondary post-tonsillectomy bleedings were observed after procedures which had been carried out with "hot" techniques: bipolar forceps or bipolar scissors; 6. Ivy's method is the recommended method of choice to examine the bleeding time.

[Laser stapedotomy--the modern solution of otosclerotic stapes fixation]. / Lézerstapedotomia--az otoscleroticus stapesfixatio korszeru megoldása.

UNLABELLED: Development of surgical treatment of otosclerotic stapes fixation has been one of the success stories of otology for the past five decades. Nowadays not only stapedectomy and partial stapedectomy, but stapedotomy can also be considered a well established otological procedure. AIM: To introduce this minimally invasive surgical technique into the Hungarian otolaryngology practice, to gain useful experiences, and to analyze the hearing improvements and postoperative complications. METHODS: The authors give account of their first clinical experiences with 14 patients with KTP laser assisted stapedotomies using the self-crimping Nitinol piston. A total of 14 patients (11 females, 3 males) who have undergone the procedure between March 2006 and April 2007 were reviewed. The average age of the patients was 42,2 years, 6 procedures were carried out on left ears and 8 on right ones. The average length of follow-up was 9 months (ranged from 6 weeks to 1 year). RESULTS: Pure tone audiograms documented a hearing threshold improvement of 21,5 dB averaged across 0,5-1-2-3 kHz frequencies. The air-bone gap improvement averaged on the same frequencies was 18,7 dB. After an average 9 months postoperative follow-up period, the average air-bone gap was < 10 dB in 85% of the patients, however, < 20 dB in 100% of the patients. As for the average air conduction result: it was < 30 dB in each patient except for one. In this series, neither facial nerve paresis nor high frequency deterioration of the bone conduction thresholds was reported in the postoperative follow-up period. CONCLUSIONS: Based on the authors' favourable experiences and the review of the literature, KTP laser assisted stapedotomy with the use of Nitinol piston has several advantages: 1) the laser-activated memory effect of the piston prevents the disadvantages of the crimping manoeuvre made around the long process of the incus; 2) vertigo, experienced in the early postoperative period is milder and takes shorter time, reducing the length of hospitalisation; 3) the procedure is cost-effective and minimally invasive; 4) application of KTP laser assures bloodless operating field and minimal cochlear trauma; 5) migration of the prosthesis can be prevented, the degree of the surrounding granulation is less; 6) high frequency hearing improvement can be achieved in the long run; 7) the frequency and seriousness of complications is less, therefore this technique can be recommended for inexperienced ear surgeons, too; 8) the procedure can be used in difficult situations, too, e.g.: in the presence of stapedial artery, obliterative otosclerosis, flooting footplate, abnormal position of the facial nerve in the middle ear, revision cases; 9) the interindividual differences of hearing results are much less. Based on their favourable initial experiences, the authors plan to conduct a long-term follow-up on greater number of patients.

Voice prosthesis insertion after endoscopic balloon-catheter dilatation in case of a stenotic hypopharyngo-oesophageal junction.

Stenosis of the hypopharyngo-oesophageal junction can be a rare complication of laryngectomy and/or partial pharyngectomy and makes the insertion of voice prosthesis extremely difficult. This study describes the authors' experiences gained by endoscopic balloon-catheter dilatation of hypopharyngo-oesophageal stenoses prior to implantation of voice prostheses in four cases. In two patients a single balloon-catheter dilatation resulted in wide enough pharyngo-oesophageal lumen on the long run. The average prosthesis wearing-times were 6.8 months in case 1 and 4.6 months in case 2, corresponding to the published literature data. In case 3, repeated dilatation of the pharyngo-oesophageal transition had proved to be unsuccessful despite taking every effort with the endoscopic balloon-catheter method. Having excised the stenotic segment, reconstruction with pectoralis major myocutaneous flap (PMMF) was indicated. Eighteen months later, a repeated restenosis was observed and a free jejunal flap needed to be performed as a final solution. In case 4, the insertion was carried out into a previously dilated jejunal free flap, which became gradually ischemic and stenotic since the major head-and neck procedure was carried out that resulted in prosthesis rejection after just 1 week. The authors emphasize that correct indication of pedicled and free flaps in head and neck reconstruction is a prerequisite from the aspect of prevention of pharyngo-oesophageal strictures. Endoscopic balloon-catheter dilatation is a safe and established method for dilatating hypopharyngo-oesophageal stenoses of different origin. The procedure provides maximum patient benefit with minimal trauma and morbidity; moreover, facilitates insertion of voice prostheses. However, a single balloon-catheter dilatation cannot always result in wide enough oesophageal lumen on the long run (case 3). Insertion of a voice prosthesis into a previously dilated ischemic jejunal segment is challenging and avoidable due to risks of complications.

Combination of ionomer cement and bone graft for ossicular reconstruction.

The aim of this study was to investigate the efficacy of the reconstruction of large ossicular chain defects with a combination of ionomer cement and an autogenous cortical bone graft. Different individual solutions are described if at least the handle of the malleus is present: restoration of a large defect of the long process of the incus, formation of the incus body and the long process, and replacement of the missing superstructure of the stapes with a short bone graft standing on the footplate. In a unique case, total reconstruction of the malleus handle was carried out. In further cases where the malleus and the incus were absent, the missing superstucture of the stapes was replaced by a bone graft fixed to the remnant of the anterior crus, supplemented with a cortical bone PORP. Between 1993 and 2005, 84 patients underwent middle ear operations with the use of ionomer cement. In 16 ears (9 males, 7 females), a combination of ionomer cement and autogenous cortical bone graft was used for ossicular reconstruction, with a documented follow-up of at least 6 months to 7 years. All operations were performed under general anesthesia. The components of the cement were mixed by hand and transferred to the bare bone surface with a curved needle. Complex structures were built up step by step. In seven cases, the tympanic membrane was simultaneously reconstructed. The postoperative air-bone gap was < 20 dB in 11/16, 68% of the cases. No columella rejection occurred. The reconstructed malleus handle is still intact, though the hearing has deteriorated. The audiological results are encouraging and a further prospective study is under design in order to analyze the efficacy of the combination of ionomer cement and an autogenous cortical bone graft for ossicular reconstruction. The simultaneous reconstruction of the superstructure of the stapes and the long process of the incus or the whole incus makes PORPs or TORPs superfluous, if at least the handle of the malleus is present.

In vivo effects of afobazole (2-mercaptobenzimidazole derivative) on the 7,12-dimethylbenz [alpha]anthracene-induced oncogene and suppressor gene expression.

BACKGROUND: Afobazole, a new 2-mercapto-benzimidazole derivative, exhibited antimutagenic activity in chromosome aberration tests and antioxidant properties. The aim of this study was to demonstrate the potential chemopreventive effect of afobazole on the level of early biological effects by analysing changes in oncogene and tumor suppressor gene expression. MATERIALS AND METHODS: Single intraperitoneal (i.p.) treatment with 7,12-dimethylbenz[alpha]anthracene (DMBA) combined with afobazole was administered to CBA/Ca (sensitive H-2K haplotype) female mice. The expression of Ha-ras and p53 was determined in the vital organs (liver, spleen, lung, kidney, thymus, lymph nodes and bone marrow) 24, 48 and 72 hours later. RESULTS: Coadministration of afobazole and DMBA resulted in a decrease of DMBA-induced overexpression of Ha-ras and p53. Reduction of the DMBA-induced gene expression was most striking when afobazole was given in parallel with DMBA. DISCUSSION: Our results strengthen the previous assumption, which was based on in vitro results, that afobazole has a chemopreventive effect in vivo.

Poland's syndrome and head-and-neck tumour: an unusual association causing a reconstruction dilemma.

Poland's syndrome is a rare congenital anomaly characterized by unilateral chest wall hypoplasia and ipsilateral hand abnormalities. The literature data suggest its sporadic nature. The prevailing theory concerning its cause is hypoplasia of the subclavian artery or its branches, which may lead to a range of developmental changes. Relationships have been demonstrated between tumours and Poland's syndrome and also between tumours and other developmental defects. The explanation may lie in abnormal homeobox and tumour suppressor genes. This paper presents the first literature report of a malignant tonsillo-lingual tumour with metastatic neck involvement in a patient with partial Poland's sequence. In consequence of the aplasia of the pectoralis major muscle, an alternative (a free radical forearm flap) to the routine head-and-neck reconstruction (pedicled pectoralis major flap) was necessitated following tumour excision and radical neck dissection. This case report surveys the diagnostic and therapeutic considerations when previously unnoticed Poland's syndrome is diagnosed in a patient with head-and-neck cancer. One year following major head-and-neck surgery, our patient is tumour-free.

Detection of osteoprotegerin and TNF-alpha mRNA in ankylotic Stapes footplates in connection with measles virus positivity.

HYPOTHESIS: Otosclerosis is a bone remodeling disorder of the otic capsule causing conductive and sensorineural hearing loss. Persistent measles virus infection of the temporal bone with increased tumor necrosis factor (TNF)-alpha and decreased osteoprotegerin mRNA expression is supposed to be the main etiologic factor in otosclerosis. BACKGROUND: Determinants of measles virus infection and reactive inflammation were studied in otosclerosis. The presence of measles virus was shown in otosclerotic patients by reverse transcriptase-polymerase chain reaction (RT-PCR) amplification of the viral RNA. No report is available, however, about the role and interactions of bone-specific cytokines in otosclerosis. METHODS: : Nucleic acid was extracted from stapes footplates of clinically otosclerotic patients. Measles virus nucleoprotein RNA was amplified by seminested RT-PCR. TNF-alpha and osteoprotegerin mRNA coexpression was detected by RT-PCR in otosclerotic bone and was correlated to measles virus positivity. RESULTS: Among 154 clinically stapes fixation otosclerotic patients, 99 stapedes contained measles virus RNA. TNF-alpha mRNA was detectable in 88 virus-positive and in 6 virus-negative stapes footplates. Osteoprotegerin mRNA expression was significantly lower in the TNF-alpha-positive specimens (P < .0001) that was independent from virus positivity. CONCLUSION: Detection of TNF-alpha mRNA demonstrates activated osteoclast functions and inflammatory pathways in otosclerotic stapes footplates associated with measles virus presence. Increased expression of TNF-alpha and its action on RANK production inhibits the protective functions of osteoprotegerin on normal bone turnover in the otic capsule.

Activated osteoclasts with CD51/61 expression in otosclerosis.

HYPOTHESIS: Stapes ankylosis is supposed to be a disease with variable histopathology caused by otosclerosis or pseudo-otosclerosis. Persistent measles virus infection of the otic capsule could induce reactivation of quiescent embryonic osteoclasts in otosclerosis. BACKGROUND: Presence of measles virus RNA was demonstrated in the footplates of otosclerotic patients by reverse-transcription polymerase chain reaction (RT-PCR). Histology of active otosclerosis is featured by the presence of numerous osteoclasts with unknown phenotype. METHODS: Nucleic acid was extracted from stapes footplates of clinically otosclerotic patients (n = 261). Genomic RNA of measles virus was amplified by RT-PCR. Amplification results were correlated to postoperative histologic and CD51/61 specific immunohistologic findings. A parallel alcalic phosphatase activity assessment was performed to evaluate the metabolic activity of osteoclasts in each section. RESULTS: Among 261 stapes fixation cases, 175 otosclerotic stapes contained measles virus RNA. Histology for virus negative stapes (n = 86) represented nonotosclerotic, degenerative disorders. Histologically confirmed otosclerosis was featured by the presence of osteoclasts with renewed, embryonic phenotype. In otosclerosis, alcalic phosphatase activity was significantly higher compared with nonotosclerotic stapes ankylosis (P < .001). CONCLUSION: The presence of CD51/61 positive osteoclasts in otosclerotic bone containing viral sequences provides the basis for an inflammatory bone remodeling disorder. Otosclerosis is a disease caused by persistent measles virus infection and reactivation of resting embryonic osteoclasts in the otic capsule.