Mometasone furoate and nasal vascularisation in allergic patients.

Angiogenesis, the growth and proliferation of new blood vessels, is important in a variety of pathophysiological processes. However the role of angiogenesis in allergic rhinitis has not been well studied. Hence, the aim of this study was to compare the vascularisation of the nasal mucous membrane of non-allergic, non-treated allergic and allergic patients treated with mometasone furoate. A small piece of the nasal mucous membrane was taken from the frontal pole of the lower nasal shell from 90 patients. The patients were divided in three groups, each containing 30 patients. First group of patients (GP1) had a negative inhalatory allergen test, patients in second group (GP2) had positive test but were not under treatment and the third group of patients (GP3) had positive results with the same test and were treated with mometasone furoate for 15 days before analysis. Immunhistochemical staining with anti-CD31 and VEGF-C was performed. Vascular phase was determined by using length density. Differences in expression of CD31 and VEGF-C were compared using one-way ANOVA and Tukey HSD post-hoc tests. Significantly lower values of CD31 and VEGF-C expression were observed in GP1 in compare with GP2 and GP3 (p < 0.001, p = 0.013, resjpectively). In GP3 the microvessel density was significantly lower than in GP2 (p < 0.001), but higher than in GP1. Our results demonstrated that 15-day treatment with mometasone furoate results in a significant reduction of the density of vascular parameters in allergic patients.

Gene amplification of epidermal growth factor receptor in atypical glottic hyperplasia.

The study searched for epidermal growth factor receptor (EGFR) gene amplification in hyperplastic glottis lesions. After classical pathohistological findings of hematoxylin-eosin (HE) slides and quantitative immunohistochemical (IHC) analysis, fluorescent in situ hybridization (FISH) was used on tissue microarrays of laryngeal hyperplastic tissue ranging from normal mucosa to abnormal and atypical hyperplastic lesions. FISH analysis of two atypical hyperplastic lesions discovered the amplification of EGFR gene while it was not found in simple and abnormal hyperplastic lesions. The results may indicate that EGFR gene amplifications could possibly correlate with the histopathologic picture. Tissue samples burdened with specific oncogen signatures like EGFR gene amplification could be detected in precancerous lesion. This might improve follow-up and treatment protocols of glottic lesions which are an everyday problem for ENT practitioners. Further research is mandatory to confirm our findings.

Juvenile angiofibroma of the maxillary sinus.

Juvenile angiofibromas are benign fibro-vascular tumours of the nasopharynx that develop in prepubertal and adolescent males. Typical symptoms are longstanding unilateral nasal obstruction occasionally followed by epistaxes and frequent severe intraoperative haemorrhage of the discovered mass. We report the case of a 14-year-old boy histologically diagnosed with a juvenile angiofibroma in spite of the atypical localisation of the polyploid mass of the left maxillary sinus.

Water related otitis externa.

Water influences skin inflammation of the external auditory canal. The common term for this illness is "swimmer's ear". Contributory factors are length of exposure to water, type of water and water pollution. The aim of the study was to compare risks for contracting the disease between patients with different exposure to swimming pool water. A retrospective case-control analysis of patients at the ENT-clinic was performed. Swimmers and water polo players swam in a swimming pool chlorinated by an automatic swimming pool cleaning system. Water sport players had a higher risk for ear skin inflammation than football players. Senior football players compared with players younger than 13 were not at increased risk. Swimmers and water polo players older than 13 were at higher risk. Swimmers were at higher risk than football players as well as water polo players. There was no difference for the risk of otitis externa between swimmers and water polo players. Swimmers and water polo players compared with other patients of the ENT-clinic were at higher risk than football players. Frequent and longer exposure to water has been proved to increase the risk of external auditory canal inflammation.

Nuclear EGFR Expression Is Associated With Poor Survival in Laryngeal Carcinoma.

The membrane EGFR (mEGFR) protein overexpression in the head and neck squamous cell carcinoma (SCC) is considered to cause increased EGFR activity which adds to tumorigenicity and therapy resistance. The mEGFR upon stimulation can translocate to the nucleus nuclear EGFR (nEGFR) where it has been associated with poor prognosis and worse survival in many cancers. The relevance of differentially located EGFR proteins in laryngeal lesions has not been studied enough and remains unclear. Aim of our study was to examine nEGFR and mEGFR protein expression as well as EGFR gene status and cell cycle proliferation markers in the laryngeal polyps, dysplasia, and SCC using immunohistochemistry and in situ hybridization. There was significantly higher frequency of strong nEGFR between SCC, dysplasia, and polyps (P<0.0001), and strong mEGFR in the SCC and laryngeal dysplasia comparing to polyps (P<0.0001). Gene amplification was confirmed only in relatively small number of SCC but not in non-neoplastic lesions. In dysplasia the statistically significant positive correlations between nEGFR, and Ki-67 (P=0.029), p53 (P=0.001), and cyclin D1 (P=0.031) were found. nEGFR and mEGFR expression showed statistically significant inverse correlation in the SCC (P=0.004) as well as nEGFR and cyclin D1 (P=0.032). Univariate statistical analysis showed statistically significant correlation between strong nEGFR protein expression and worse overall survival in laryngeal SCC, alone or in coexpression with strong cyclin D1 and high Ki-67 (P=0.025, P=0.046, P=0.043, respectively). Our data show that nEGFR cellular localization might influence biology of the laryngeal carcinogenesis and is indicator of poor survival.

Epidermal growth factor receptor protein expression and gene amplification in normal, hyperplastic, and cancerous glottic tissue: immunohistochemical and fluorescent in situ hybridization study on tissue microarrays.

AIM: To evaluate the importance of epidermal growth factor receptor (EGFR) protein overexpression and gene amplification in carcinogenesis of glottic cancer. METHOD: In order to evaluate EGFR expression at protein and gene level, immunohistochemical (IHC) analysis and fluorescent in situ hybridization (FISH) were performed on tissue microarrays of laryngeal tissue (145 samples) -- 38 samples of normal mucosa, 46 samples of hyperplastic lesions, and 61 samples of cancerous lesions. RESULTS: Membranous (mEGFR) and cytoplasmic (cEGFR) EGFR expression was significantly different between the analyzed groups. The differences were most striking in the suprabasal-transforming zone. IHC evaluation showed that high and low mEGFR staining contributed to the differentiation of dysplastic lesions, simple hyperplasia, and cancerous tissue, as well as between different degrees of atypia in hyperplastic lesions (P<0.050). EGFR gene amplification was not found in simple and abnormal hyperplastic lesions, but it was confirmed in 2/21 atypical hyperplasias, indicating that gene amplification can facilitate identification of malignant potential in hyperplastic lesions. In cancerous tissue, EGFR gene amplification was found in 8/50 samples. EGFR gene amplification was found in preinvasive cancer in one patient. In invasive carcinomas, gene amplification was not associated with stage or grade. Carcinomas with gene amplification showed significantly higher cEGFR expression (basal layer P=0.003; suprabasal layer P=0.002). CONCLUSIONS: This study confirmed an increase in EGFR protein expression and gene amplification with the increase in biological aggressiveness of glottic lesions. A correlation between EGFR gene amplification and protein expression was established. Gene amplification proved to be an early event in glottic carcinogenesis, indicating its importance for glottic cancer prevention, early detection, and protocol selection.

Immunohistochemical analysis of vocal cord polyps applying markers of squamous cell carcinogenesis.

OBJECTIVE: The aim of the study was to perform a pathohistological and immunohistochemical analysis of squamous cell (SC) carcinogenesis markers on epithelial linings of vocal cord polyps. The vocal box, being a heavily burdened organ with intensive cell renewal and regenerative processes, is therefore a favourable environment for constant epithelial growth and hyperplasia. In our ongoing projects on laryngeal carcinogenesis and research on laryngeal tissue, we encountered atypia on diagnosed nodules and polyps that are usually considered as benign formations, resulting from the above-mentioned cell renewal and regeneration, which lead to further investigation. The purpose was to see if changes in molecular markers of SC carcinogenesis follow, or, may appear in immunohistochemical (IHC) analysis, before histological atypia in standard haematoxylin-eosin (HE) staining, and contribute in early diagnosis of potentially suspect polyps. METHODS: After classical pathohistological (PH) analysis on HE slides, IHC analysis of EGFR, cyclin D1, p53, Ki-67, and IMP3 was performed on tissue microarrays of laryngeal tissue (50 samples), ranging from normal to hyperplastic lesions with no atypia (34 samples), low-grade atypia (11 samples), and high-grade atypia (5 samples). RESULTS: This study established an increase and correlation of EGFR, cyclin D1, p53, Ki-67 and IMP3 IHC expressions with pathohistological findings of dysplasia in glottic polypoid lesions. Low and high-grade dysplasia had statistically higher percentages of EGFR-positive cells than normal epithelium and simple hyperplasia (SH) (low vs. normal/SH P = 0.007; high vs. normal/SH P = 0.001). High-grade dysplasia had statistically more positive cells than low-grade dysplasia (P = 0.004), and low-grade dysplasia had statistically more positive cells than specimens without atypia (P = 0.007). The percentage of positive cells was statistically higher for cyclin D1, p53 and Ki-67 in high-grade dysplasia versus low-grade dysplasia (cyclin D1 P = 0.011, p53 P = 0.002; Ki-67 P = 0.026; respectively) and versus normal epithelium and SH (cyclin D1 P = 0.003; p53 P = 0.001; Ki-67 P = 0.002; respectively). An increase of IMP3-positive cells with an increase of atypical changes in the laryngeal epithelium, from superficial towards basal layers was noticed, contrary to the usually seen positivity pattern of SC carcinogenesis markers from basal to superficial layers. A statistically significant difference of IMP3 IHC staining between the pathohistological groups (P = 0.003) was recorded. CONCLUSION: Only polyps that present with simple hyperplasia as the greatest mucosal change can be considered as benign formations. Pathohistologically detected atypia in polypoid changes of vocal cords, confirmed by molecular atypia with an increase of SC carcinogenesis markers, suggest their inclusion in studies of laryngeal carcinogenesis. Our results suggest that in problematic cases IHC analysis could be of interest in detection of biological aggressiveness in polypoid laryngeal tissue and beneficiary for polyp patients' follow-up. Further research of laryngeal carcinogenesis markers and their meaning in fibrovascular polyps is of interest.

Merkel cell carcinoma arising in the ear canal.

A case of rare tumor, Merkel cell carcinoma, located in the ear canal of a 25-year-old woman is presented. A polypoid tumor mass was extirpated, and tympanoplasty was done at the first operation, whereas at the second operation, all the bones of the ear canal were removed. Epitympanum and cavum were filled with tumor, and the tumor mass was removed in toto. The histopathology and immunohistochemical staining characteristics of tumor confirmed the presence of Merkel cell tumor. Postoperatively, radiation therapy to the tumor bed was completed. There was no clinical or radiographic evidence of recurrence or metastasis of Merkel cell tumor for 3 years.

Nasopharyngeal angiofibroma with intracellular accumulation of SPARC - a hypothesis (SPARC in nasopharyngeal angiofibroma).

Nasopharyngeal angiofibroma is a histologically benign tumor composed of stroma and vessels. The vascular component of the lesion is prone to bleeding and responsible for its clinical "malignancy". Some nasopharyngeal angiofibromas are resistant to surgical therapy because of extensive growth and occasionally bone destruction. It has been shown that molecular factors supporting residual tissue after incomplete surgery might be targeted with pharmacotherapy as a cell based therapy. Because the cell of origin of nasopharyngeal angiofibroma is not recognized yet, it would be of interest to discuss molecule(s) relevant to all the cell components of the growth. Such molecule(s) may also regulate bone homing of the tumor. We propose that in nasopharyngeal angiofibroma the molecule responding to the cues mentioned above is SPARC (secreted protein acidic rich in cystein). We discuss SPARC-enabling formation of molecular complexes important for the angiogenic events and present nasopharyngeal angiofibroma as a hyperplastic angiogenic machinery or a "soil" without "seed". Therapeutic targeting of SPARC in nasopharyngeal angiofibroma would be targeting of a molecule at the roots of cooperation between stromatogenesis and angiogenesis, coexpressed with Ki67 in the vascular compartment. Considering the intracellular accumulation of SPARC, the benefit of (anti) SPARC therapy in nasopharyngeal angiofibroma is yet to be proved.

Maculopapular eruption secondary to itraconazole.

Adverse cutaneous reactions to itraconazole are known to be quite rare. We report a case of maculopapular reaction caused by itraconazole. On the 7th day of itraconazole therapy for hand onychomycosis, in a 39-year-old woman pruritus occurred with a subsequent morbiliform, symmetric, maculopapular eruption on the upper torso, neck, trunk and pressure-bearing areas. Eruption progressed, becoming confluent and spreading to extremities. Due to increasing indications for the administration of itraconazole its increased usage as well as the possibility of allergic reactions should be expected even if these are a rare event.

Quantitative analysis of nasal vascularization in allergic patients treated with mometasone furoate.

The purpose of this study was to compare vascularization of the nasal mucous membrane among non-allergic, non-treated allergic and allergic patients treated with mometasone furoate, by means of the stereology method in quantitative analysis. Three groups of patients (GP), each containing 10 patients were examined. The first group (GP 1) had a negative inhalatory allergen test while the second (GP 2) and third (GP 3) group both had positive results with the same test. GP 3 included allergic patients treated with mometasone furoate for 15 days before analysis, when a small piece of the nasal mucous membrane was taken from the frontal pole of the lower nasal shell. The specimens were examined immunohistochemically for expression of CD31 and VEGF-C. Vascular phase was determined by using length density (L(v)). Differences in CD31 and VEGF-C expression were compared using one-way ANOVA and Tukey HSD post-hoc tests. CD31 expression in GP 1 had significantly lower values than in the GP 2 and GP 3 groups (p < 0.001). VEGF-C expression in GP 1 was significantly lower than in GP 2 (p = 0.007), but not in GP 3 (p = 0.292). We have shown that 15-day treatment with mometasone furoate results in a significant reduction of the density of vascular elements in allergic patients.

Cytoplasmic EGFR staining and gene amplification in glottic cancer: a better indicator of EGFR-driven signaling?

Although enhanced epidermal growth factor receptor (EGFR) signaling has been connected with glottic cancerogenesis, the precise mechanisms of its activation still remain unclear. The aim of the present study was to examine EGFR on protein level, confronting cellular pattern of expression and EGFR gene amplification in glottic carcinomas. Tissue microarray technology was applied for uniformity of results. Biopsy specimens of patients with glottic squamous cell carcinoma and simple hyperplasia (control samples) were immunostained for EGFR. Immunohistochemical EGFR reaction was analyzed as membrane and cytoplasm positive and compared with the presence of gene amplification obtained by fluorescent in situ hybridization (FISH) analysis, obtained previously on a large group of patients. The cytoplasmic distribution of the EGFR staining appeared as a primary property of some squamous carcinoma cells; different from the membranous reaction, the reactions were mutually exclusive. Significantly higher scores of cytoplasmic EGFR staining were found in carcinomas with gene amplification when the cell reaction was examined in the basal and suprabasal layer. Our results suggest that EGFR expression in squamous cell carcinoma is different with regard to tumor cell position in carcinoma with ERGF gene amplification, which could be a new indicator of differently driven EGFR signaling in glottic cancer. Such results with cellular pattern distribution of EGFR protein are worthy of further research.

Cartilage palisade tympanoplasty in children and adults: long term results.

OBJECTIVE: To show long-term anatomic and functional results of full thickness cartilage palisade tympanoplasty in children and adults. METHODS: In 51 patients (56 ears); 9 children (12 ears) and 42 adults (44 ears) full thickness cartilage palisade tympanoplasty and interposition with malleus head autograft was performed. On average 11 years after the tympanoplasty, an otomicroscopy and a tonal audiogram were done to assess anatomic and functional results. RESULTS: Anatomic results of 56 ears: 40 (71.43%) tympanic membranes have no anatomic irregularities; 14 (25.00%) have cartilage resorption (11 of them minor and 3 major resorptions), 2 (3.57%) have secondary perforation. In the group of children all ears tympanic membrane were with no or minor resorption and no perforations. Functional results (51 audiograms performed: in children 12 and in adults 39): pre- and post-operative average pure tone average air-bone gaps were 27.29 ± 10.26 and 10.73 ± 7.90 dB, respectively. In the group of children pre- and post-operative average pure tone average air-bone gaps were 29.44 ± 10.30 and 6.81 ± 3.47 dB, respectively. In the group of adults pre- and post-operative pure tone average air-bone gaps were 26.63 ± 10.30 and 11.93 ± 8.50 dB, respectively. The differences between the two groups preoperatively (z=0.733; p=0.463) and postoperatively are irrelevant (z=1.723; p=0.085). The hearing gain is bigger in children (F=4.788; p=0.033). CONCLUSION: The full thickness cartilage palisade tympanoplasty with malleus autograft interposition is also nowadays a successful method in solving of an advanced ear pathology also in children.

The clinical status of the eardrum: an inclusion criterion for the treatment of chronic secretory otitis media in children.

OBJECTIVE: To investigate if the clinical status of the eardrum could be an inclusion criterion for the therapy of chronic secretory otitis media (CSOM). To compare the results of treating CSOM by adenoidectomy and by adenoidectomy in combination with tympanostomy tubes in two groups of patients chosen according to that criterion. METHODS: 161 ears in 87 children were treated for CSOM. An otomicroscopic examination showed there were no pathological changes on the tympanic membrane (signs of adhesive process, malleus rotation, and dangerous attic retractions). The patients were randomly divided into two groups: the first group of 59 ears was treated by myringotomy and tympanostomy tubes and adenoidectomy, while the other group of 102 ears was treated only by adenoidectomy. At least 6 months after the treatment, otomicroscopy and audiological assessments were performed in order to show the resolution of the middle ear effusion (MEE), audiological results and incidence of clinical sequelae of the eardrum. RESULTS: The resolution of MEE by adenoidectomy alone was not significantly different from the results of treatment by adenoidectomy and tympanostomy tubes (z=1.565; p=0.0587). There were no differences in pure tone audiometry between the two methods of treatment. Only at the frequency of 2000 Hz (t=2.173; p=0.031) in treatment with adenoidectomy and tympanostomy tubes the values of air-bone gap (ABG) were lower. Sequelae: scars of the eardrum (chi-square=28.107; ss=1; p<0.001) and attic retractions (chi-square=4.592; ss=1; p=0.032) were more often in treatment with tubes. The incidence of clinical sequelae on the eardrum after treatment by tubes was commented on. CONCLUSION: A criterion that could influence the approach to the therapy of CSOM in children.

Radiofrequency-induced thermotherapy of nasopharyngeal angiofibroma and immunohistochemical analysis of vessel proliferation: a case report.

INTRODUCTION: Nasopharyngeal angiofibroma presents with symptoms of nasal obstruction and epistaxis. The treatment of choice is embolization followed by surgery. CASE PRESENTATION: A 52-year-old man underwent surgery for nasopharyngeal angiofibroma after adjuvant radiofrequency-induced thermotherapy. To the best of the authors' knowledge, this is the first case of angiofibroma with clinical follow-up after thermocoagulation therapy supported by quantitative, double immunohistochemistry. We found this case of angiofibroma to be of interest owing to the presentation of symptoms leading to biopsy, the pathohistological observations obtained with synchronous Ki67/cluster of differentiation 34 and Ki67/smooth muscle actin immunohistochemistry and high pericyte proliferation. CONCLUSION: Coagulation of angiofibroma vessels followed by acquisition of a thick mantle of pericytes in a patient with a nasopharyngeal growth suggests that radiofrequency-induced thermotherapy could be a useful, palliative therapy for bleeding nasopharyngeal angiofibroma, supporting vessel maturation prior to surgical tumor removal.