Clinical characteristics of patients with granulomatosis with polyangiitis and microscopic polyangiitis in ENT practice: a comparative analysis.

ENT manifestations are commonly observed in patients with small vessel vasculitis (SVV). The main aim of this study was to analyse and present the clinicopathological characteristics of individuals with SVV emphasising otorhinolaryngological symptoms. This study evaluated 64 patients, 41 with granulomatosis with polyangiitis (GPA) and 23 with microscopic polyangiitis (MPA). Herein, we compare the clinicopathologic features of GPA and MPA. The average age at diagnosis was 50.2 and 56.2 years, for GPA and MPA, respectively. 57 patients (89%) were antineutrophil cytoplasmic antibody (ANCA) positive, 34 (59.6%) for anti-proteinase 3 (PR3)-ANCA and 21 (36.8%) for myeloperoxidase (MPO)-ANCA. 7 patients (10.9%) were ANCA negative. The most commonly affected organs were lungs (76.56%), ear, nose, throat (ENT) (75%) and kidneys (73.44%). ENT disorders mainly appeared as chronic rhinosinusitis and epistaxis and preceded SVV diagnosis by an average 14.4 months. In the majority of patients, ENT disorders were the first symptoms of SVV and preceded its systemic transformation. Pulmonary, ENT and nervous manifestations were more common in GPA, whereas the prevalence of renal, gastrointestinal, cutaneous, cardiovascular and ocular disorders was higher in MPA. The results of our study emphasise the high prevalence of ENT symptoms in patients with SVV, especially in those with GPA. We highlight the significant role of the otorhinolaryngologist in early SVV diagnosis and management. Any patient with persistent ENT symptoms or ENT dysfunctions not responding to standard otorhinolaryngological treatment should be precisely and rapidly evaluated for the presence of systemic dysfunctions (especially renal and pulmonary). Realising the differences and similarities between GPA and MPA is crucial in undelayed SVV diagnosis and proper treatment.

Diabetes and Cancer: a Review of Current Knowledge.

Diabetes mellitus (DM), one of the most common life-threatening illnesses worldwide, is a group of metabolic diseases, characterized by sustained hyperglycemia. The global prevalence of diabetes mellitus among adults reached 387 millions in 2014 and is still rising. It is suggested there is a strong association between diabetes mellitus (especially type 2 diabetes mellitus) and carcinogenesis. The possible biological links between diabetes mellitus and cancer comprise hyperinsulinemia, hyperglycemia and fat-induced chronic inflammation. Although, the strongest association refers to pancreas and liver, there are many other organs involved in carcinogenesis in diabetic patients including breast, endometrium, bladder and kidney.Recent studies suggest that there is also association between cancer incidence and anti-diabetic medications. It was observed that some medications decrease the risk of carcinogenesis and some increase that risk. The majority of studies concern metformin, a drug of choice in type 2 diabetes mellitus, and its anti-neoplastic and tumor-suppressing activity. The positive effect of metformin was found in numerous researches investigating breast, pancreas, liver, colon, ovaries and prostate tumors.Because a variety of studies have suggested that diabetes mellitus and cancer are frequently coexisting diseases, recently published studies try to explain the influence of diabetes mellitus and anti-diabetic medications on carcinogenesis in different organs.We present the review of the latest studies investigating the association between both diabetes mellitus and anti-diabetic medications and cancer incidence and prognosis.Particularly we highlight the problem of concomitant head and neck cancers in diabetics, rarely analysed and often omitted in studies.

Vitamin D analogs decrease in vitro secretion of RANTES and enhance the effect of budesonide.

PURPOSE: Eosinophils appear to be central inflammatory cells in the pathogenesis of rhinosinusitis with nasal polyps (NP). One of the most predominantly recognized eosinophil chemoattractants is RANTES. The aim of this study was to assess the influence of vitamin D (VD) derivates on RANTES expression in the culture of nasal polyp fibroblasts. MATERIAL AND METHODS: NP fibroblast cell cultures derived from 16 patients with NP were first stimulated with bacterial LPS and than incubated in increasing concentrations (from 10(-7)M to 10(-4)M) of calcitriol, tacalcitol or budesonide and in combination with one of VD derivate with budesonide in 1:1, 1:3 and 3:1 ratios. Quantitative analysis of RANTES level was conducted in culture supernatants using an ELISA method. RESULTS: The highest calcitriol concentration (10(-4)M) as well as tacalcitol at 10(-5)M and 10(-4)M reduced RANTES production significantly compared to the control (201.1pg/ml, 338.7pg/ml, 211.3pg/ml v 571.78pg/ml; p<0.05). Budesonide and calcitriol administered in 1:3 ratio and budesonide and tacalcitol in 1:1 and 1:3 reduced RANTES concentration significantly better than each of the drug used in monotherapy (p<0.05). Budesonide and tacalcitol in 1:1 and 1:3 ratios suppressed RANTES production to the lowest level (171.8±97.6pg/ml and 178.7±105.22pg/ml, respectively). CONCLUSION: Active VD compounds via downregulation of RANTES production exert a potential role as a complementary element in the therapy of chronic rhinosinusitis with NP. Compounds consisting of budesonide and VD derivate have an advantage over both drugs used in monotherapy.

Vitamin D derivatives: calcitriol and tacalcitol inhibits interleukin-6 and interleukin-8 expression in human nasal polyp fibroblast cultures.

PURPOSE: Biologically active vitamin D3 (VD) derivatives possess modulatory activities on immunological and inflammatory responses which can be reflected by altered levels of pro-inflammatory chemokines. Nasal polyposis (NP), defined as a chronic inflammatory process of upper respiratory system, could be influenced by VD derivatives. The purpose of this study was to investigate the influence of 1alpha,25-dihydroxyvitamin D3 (calcitriol) and 1alpha,24(R)-dihydroxyvitamin D3 (tacalcitol) on the secretion of IL-6 and IL-8 by fibroblasts derived from NP. MATERIAL AND METHODS: The study involved 12 fibroblast cultures derived from NP samples obtained from surgically treated patients. Measurements were performed on the polyp cells after the 6-9 passages. Culture stimulation involved treatment with tacalcitol and calcitriol at a defined strength (from 10(-7)M to 10(-4)M). IL-6 and IL-8 concentrations were estimated with ELISA. RESULTS: Treatment with calcitriol or tacalcitol inhibits the synthesis of both IL-6 and IL-8 compared to the control group. The dose dependence of this effect has been confirmed. VD derivatives influence was marked at higher concentrations. Significant interleukin decrease was observed at 10(-5) and 10(-4) for calcitriol and 10-4 in the case of tacalcitol. CONCLUSIONS: The present study demonstrates that calcitriol and tacalcitol are capable of affecting pro-inflammatory cytokine (IL-6 and IL-8) levels in NP cultures. Our data imply a potential therapeutical application of topical VD derivates in NP and warrant further investigation.

The role of computer-assisted analysis in the evaluation of nuclear characteristics for the diagnosis of precancerous and cancerous lesions by contact laryngoscopy.

PURPOSE: Contact endoscopy (CE) through the direct contact with the surface of the mucosa enables in vivo visualization of upper epithelial layers. There is a broad spectrum of laryngeal pathologies, as has been confirmed by earlier CE reports. The aim of the study was to resolve some of the limitations of CE through the application of computer-assisted image analysis. Quantitative and qualitative evaluation of nuclei was applied in the diagnosis of precancerous and cancerous lesions. MATERIALS AND METHODS: Fifty four patients with various laryngeal pathologies were included in the study. Paraffin section histopathology showed 15 benign lesions, 12 precancerous lesions (5 mild and 7 severe dysplasias) and 27 invasive squamous cell cancers (SCC). After staining the mucous with 1% methylen blue, examination with contact endoscope (Karl Storz, Germany) connected to the C-7070 Wide Zoom Olympus high-resolution camera was performed. RESULTS: The most discriminative parameters were revealed to be as follows: nucleus area (p<0.001), nuclei density index (p<0.001), elongation coefficient (p<0.05), nucleus area to equivalent area ratio (p<0.05). Computer-assisted image analysis composed with data mining techniques is presented for nuclei categorization. CONCLUSIONS: We established that computer-aided image analysis can indicate, with a high level of reliability, cases of severe dysplasia and carcinoma. By implementing the technique described in this paper, we can substantially increase the sensitivity of CE.

Bcl-Xl protein expression in laryngeal squamous cell carcinoma.

The Bcl-2 family of proteins regulate one of the steps in an evolutionary conserved apoptotic pathway. The long splice variant of Bcl-X (Bcl-Xl) is a potent antagonist of apoptosis. The aim of the study was to evaluate the relation between the presence of immunohistochemically detectable Bcl-Xl protein in laryngeal squamous cell carcinomas (LSCCs) and clinicopathological data, as well as DNA ploidy status and proliferative activity. In 50 specimens of LSCC, Bcl-Xl protein expression was evaluated immunohistochemically. Proliferative activity (SG2M-phase index) and DNA ploidy were measured by flow cytometry. In our study, Bcl-Xl protein expression decreased with decreasing tumour differentiation (P = 0.04). The majority of patients with Bcl-Xl protein immunoreactivity had no metastatic lymph node involvement (P = 0.01). Other factors such as age, gender, primary tumour size (pT) and type of cancer (keratinizing/non-keratinizing) were not associated with Bcl-Xl protein level. There was no correlation between Bcl-Xl protein and SG2M-phase index or DNA ploidy status. Our findings show that expression of Bcl-Xl protein is increased in a great fraction of laryngeal cancers. Further studies, however, are needed to clarify association between Bcl-Xl protein expression and clinical course of patients.

Laryngeal manifestations of gastroesophageal reflux disease in children.

Although the association between gastroesophageal reflux disease (GERD) and laryngeal disorders in adults is well established there is still a lack of information concerning the true extent of the laryngeal complications of GERD in children. The aim of this study was to determine the laryngeal status of children with diagnosed GERD. We sought to identify the initial appearance of their larynges and then to determine the clinical response to antireflux therapy. GERD was recognized in 90/100 children examined. Using 24-h pH monitoring we found that most of the patients experienced episodes of gastroesophageal reflux during the daytime when they were in an upright position. The hallmark of GERD affecting the larynx in our group was posterior laryngitis, which is characterized by erythema of the mucous membrane overlying the arytenoid cartilages and the posterior mucosal wall of the glottis. The findings regarding the effectiveness of therapy were that, in children with severe laryngeal alterations, voice quality improved significantly after 12 weeks of antireflux treatment (p < 0.001) and laryngeal status was significantly better after 6 weeks of treatment (p < 0.001). This study provides evidence that gastroesophageal reflux in children is the underlying cause of inflammatory and morphological lesions, and that antireflux treatment is effective in reducing or eliminating these lesions.

A comparative study of cefaclor vs. amoxicillin/clavulanate in tonsillopharyngitis.

BACKGROUND: Acute pharyngotonsillitis (APT) is one of the most common inflammatory processes of adults and children in an outpatient setting. Increasing failure rates, hypersensitivity to penicillin, the required multiple daily doses and common side effects lead to poor patients compliance and thus inadequate treatment duration, providing therefore ground for considering alternative antimicrobial agents. MATERIAL AND METHODS: This multicenter, randomized, single blind study was undertaken in order to compare efficacy and safety of cefaclor (375 mg BID) and amoxicillin/clavulanate (625 mg BID) in 10 days treatment regiment of ambulatory patients with APT. A total of 200 patients (age range between 12-65 years) with symptoms of APT and positive antigen strep test were enrolled into the study. Clinical and bacteriological responses were assessed after the end of treatment (14th-18th day) and at the follow-up visit (38th-45th day). All GABHS strains, isolated from throat cultures, were tested for in vitro sensitivity to the antibiotics used in the study and no strain was found resistant to both antibiotics. RESULTS: The results indicated that both antibiotics had high--almost 99% effectiveness at the post therapy visit. On the follow up visit an increased tendency of relapses was observed in the amoxicillin/clavulanate treated group, compared to cefaclor treated group (8.33% vs 3.29%). Relative risk of relapse in patients treated with amoxicillin/clavulanate was 2.6 greater compared to cefaclor. There were significantly higher rates of gastrointestinal adverse events in group treated with amoxicillin/clavulanate (29/97 patients; 29.89%) compared to cefaclor (16/95 patients; 16.84%) - p< 0.03. Frequency of other adverse events did not differ significantly between the groups. CONCLUSIONS: Cefaclor and amoxicillin/clavulonate provide a clinically and bacteriologically effective treatment for patients with pharyngotonsillitis caused by GABHS, but cefaclor treatment is significantly safer in regard to gastrointestinal side effects.

Microsatellite and chromosome instability in squamous cell laryngeal carcinoma.

Head-and neck squamous cell carcinoma (HNSCC) represents almost 5% of all malignancies in Europe. The aetiology of HNSCC is complex, with both genetic and mutagenic factors involved. The aim of the present study was to investigate the loss of heterozygosity (LOH), mainly at tumour suppressor loci (using markers D1S2883, D2S123, D3S1611, D5S346, D7S501, D8S254, TP53, NM23), microsatellite instability (BAT25, 26, 40) and (bleomycin test) in patients with squamous cell larynx cancer. In a group of 20 patients LOH was observed mainly at the loci 3p (64.7%), 8q (71.4%), 17q (M1-30.8%, M2-25%, M3-38.5%). Despite chromosomal instability detected by bleomycin no microsatellite instability was observed.

Expression of type IV collagen and matrix metalloproteinase-2 (type IV collagenase) in relation to nodal status in laryngeal cancer.

Laryngeal carcinoma has a lower incidence of neck metastases than other malignant carcinomas of the head and neck region. However, some cases are very aggressive, showing neck metastases even in the early stages. In this study the expression of collagen IV and type IV collagenase (MMP-2) were examined immunohistologically in 50 patients with laryngeal carcinomas, and the results were compared with the incidence of neck metastases and other clinicopathological factors. The correlation between collagen IV expression and the existence of nodal metastases was statistically significant (P < 0.001). There was also significant correlation between collagen IV expression and the histological grading of the tumour. There was a tendency for samples with continuous collagen IV staining to have no matrix metalloproteinase-2 (MMP-2) immunoreactivity. No significant correlation was seen between MMP-2 protein expression and clinicopathological parameters although the correlation between MMP-2 and existence of nodal metastases was statistically borderline (P = 0.07). Multivariate analysis of the clinicopathological factors that may have an influence on the nodal status in laryngeal cancer revealed that, apart from T stage, collagen IV pattern in the basement membrane surrounding nests of carcinoma is an important prognostic factor.

Bleomycin-induced chromosome aberrations in head and neck cancer patients analyzed by classical cytogenetics and FISH.

Individual sensitivity to mutagens has been considered to play an important role in head-and-neck squamous cells carcinoma (HNSCC) development. The bleomycin test was introduced for establishing constitutional susceptibility to mutagens (T.C. Hsu, D.A. Johnston, L.M. Cherry, D. Ramkisson, S.P. Schantz, J.M. Jessup, R.J. Winn, L. Shirley, C. Furlong, Sensitivity to genotoxic effects of bleomycin in humans: possible relationship to environmental carcinogenesis, Int. J. Cancer 43 (1989) 403-409). Its criteria are based on scoring of chromosome aberrations (CAs, mainly breaks) in Giemsa-stained chromosomes. Fluorescence in situ hybridization (FISH) offers an easy method for analysis of translocations, acentric fragments and dicentrics. In the present study FISH was applied in the analysis of bleomycin-induced CAs of the HNSCC patients and controls. The results proved that FISH is a complementary method to the classical staining in monitoring of bleomycin-induced CAs.

[Androgens and laryngeal cancer]. / Androgeny a rak krtani.

The article concerns relations between larynx cancer and androgenic activity in men. Up till now the role of androgens in laryngeal carcinogenesis has not been established. Authors point out to andropenia (gonadal and supracortical) in elderly males and its influence on larynx cancer occurrence in the course of aging. Results of androgen receptor studies in unchanged and neoplastic tissue of the vocal organ are described. There is presented data on serum androgen concentrations in healthy men and patients with laryngeal neoplasms. The necessity of further studies of the larynx cancer's hormone-dependence is underlined.

Immunohistochemically stained markers (p53, PCNA, bcl-2) in dysplastic lesions of the larynx.

The percentage of malignant transformation of laryngeal dysplastic lesions is difficult to estimate. There is a need for new histological markers which could enable more objective assessment of the premalignant stages of the larynx and help in estimation of the potential of future neoplastic progression. We performed a retrospective study to determine whether immunohistochemical staining for the proliferating cell nuclear antigen (PCNA), tumour suppressor gene protein p53 and antiapoptotic protein bcl-2 may be prognostic factors in laryngeal epithelial lesions. Staining was performed on 57 paraffin-embedded biopsies from patients with clinically detected precancerous stages of the larynx. Histopathologic examination revealed normal epithelium in six cases, mild dysplasia in 20 cases, moderate dysplasia in 18 cases, severe dysplasia in seven cases, CA in situ in four cases, papilloma in one case and CA invasivum in one case. The p53 count in mild and moderate dysplasia was 26.8 and 38.6%, respectively. This difference was statistically significant. There was significant correlation between PCNA and p53 scores. There was also a relationship between the scores of these markers and bcl-2 expression. In ten out of 45 cases of dysplastic lesions the invasive cancer developed in 4 years of follow-up. The correlation between PCNA score and malignant progression of the dysplastic lesions was on the statistical borderline. There was significant relationship between malignant transformation and age of the patients.

Epidermal growth factor receptor (EGFR), proliferating cell nuclear antigen (PCNA) and Ki-67 antigen in laryngeal epithelial lesions.

The epidermal growth factor receptor (EGFR), proliferating cell nuclear antigen (PCNA) and Ki-67 immunostaining in paraffin sections from 154 cases of laryngeal squamous cell carcinoma, 25 specimens of normal and hyperplastic laryngeal epithelium, and 21 preneoplastic lesions was examined. The difference of EGFR expression and PCNA score between laryngeal cancer and dysplastic lesions vs normal and hyperplastic epithelium was significant. There was significant difference in Ki-67 score between malignant vs premalignant lesions and normal and hyperplastic epithelium. There was significant correlation between PCNA score and histopathological grading of the tumour. The highest PCNA expression was detected in stage G3. Our findings have shown that PCNA and Ki-67 staining can be used as a marker of cell proliferative activity in laryngeal epithelial lesions. EGFR, PCNA and Ki-67 expression correlate with severity of laryngeal lesions. PCNA immunostaining can aid in estimating the histological grade of malignant lesions.

C-erbB-2 immunostaining in laryngeal cancer.

Tumour progression is strongly associated with a series of specific genetic changes in protooncogenes and tumour suppressor genes. One of the potential factors involved in tumorogenesis of squamous cell carcinomas is protooncogene c-erbB-2 (also known as neu or HER2). The authors analysed the expression of c-erbB-2 oncoprotein in 154 cases of laryngeal squamous cell carcinomas and its relationship to the clinical outcome of the patients. The difference in c-erbB-2 oncoprotein expression between the control group and cancer patients was on the statistical borderline (p = 0.0470). There was no significant correlation between c-erbB-2 expression and sex and age of the patients. T stage, lymph node status, site and histopathological grading of the tumour and clinical outcome of the patients. Univariate analysis revealed no correlation between c-erbB-2 expression and survival rates. We conclude that immunohistological examination of c-erbB-2 on paraffin section is not a valuable prognostic factor in laryngeal carcinoma.

[Analysis of voice disorders in teachers treated in the Phoniatric Laboratory of the Otolaryngology Department AM in Wroclaw]. / Analiza schorzen narzadu glosu u nauczycieli leczonych w Pracowni Foniatrii Katedry i Kliniki Otolaryngologii AM we Wroclawiu.

Analysis of voice disorders in 898 teachers was performed. In all cases otolaryngologic, videostroboscopic and phoniatric examinations were completed. There was prevalence of women at the age ranged from 46 to 56 years. Majority of morphologic changes included Reinkes oedema (120 cases), chronic simple laryngitis (109 cases), vocal nodules (95 cases), chronic hypertrophic laryngitis (70 cases) and laryngeal polyps (35 cases). In 175 cases vocal insufficiency of glottis and in 57 cases functional disorders were diagnosed. In 131 cases no morphologic and functional changes were found. In the group of teachers the incidence of vocal insufficiency was higher than in control group. The analysis of the examined teachers revealed that professional disease was confirmed in 33% of cases. Majority of them included vocal nodules and chronic hypertrophic laryngitis.

Laryngeal cancer in Lower Silesia: descriptive analysis of 501 cases.

This paper presents a descriptive analysis of 501 cases of laryngeal cancer. The patients were classified according to their age, sex, primary tumour localisation and stage. There were 448 males and 53 females, with a male-to-female ratio of 8.5:1. The peak incidence of cancer was detected in the 6th and 7th decades of age. The most common primary tumour localisation was the glottis. Three-hundred-and-forty patients presented at advanced tumour stages (T3/T4). The proportion of patients presenting matastatic neck nodes was 29.3% and the incidence of metastatic lymph nodes increased with increasing T stage. Histopathological analysis revealed that 98% of tumours were squamous cell carcinomas. There were 125 well-differentiated, 235 moderately differentiated and 133 poorly differentiated carcinomas. Among other tumours, there was 1 adenoid squamous cell carcinoma, 1 giant cell carcinoma, 1 adenoma pleomorphicum, 1 adenoid cystic carcinoma (cylindroma), 1 haemangiopericytoma, 1 verrucous cell carcinoma, 1 lymphoepithelioma and 1 granular cell tumour.

Prognostic value of nucleolar organiser regions (AgNORs) in laryngeal cancer.

The argyrophilic nucleolar organizer regions (AgNORs) of 154 biopsy specimens of laryngeal squamous cell carcinoma were examined. The silver colloid staining technique was used. For the control, normal laryngeal epithelium obtained from 25 patients with benign lesions of the larynx was examined. There was significant difference in mean AgNORs count between control group and cancer patients. No significant correlation was found between AgNORs count and patients' age and sex, tumour site, T stage and lymph node metastasis. There was a significant correlation between AgNORs number per cell and tumour histological grading. The mean number of AgNORs per nucleus was 3.85 +/- 2.09 in patients with poor and 2.47 +/- 0.71 in patients with satisfactory clinical outcome after treatment. Significant correlation between the mean AgNORs number and survival in univariate and multivariate analysis was documented. Among clinical features the lymph node status and the T stage were important prognostic factors. We conclude that AgNORs may be a potential prognostic marker in laryngeal cancer.

Proliferating cell nuclear antigen in laryngeal cancer.

The expression of proliferating cell nuclear antigen in paraffin sections from 154 cases of laryngeal squamous cell carcinoma were examined. There was significant difference in PCNA expression between the control group and cancer patients (p < 0.001). The mean score of PCNA was higher in patients with poor prognosis than in patients with satisfactory outcome after treatment (p < 0.05). There was no significant correlation between the PCNA count and the patient's age and sex, T and N stage and site of the tumour. Univariate analysis revealed that the PCNA score correlated with the patients' survival rates. In multivariate analysis the prognostic value of PCNA was on the statistical borderline (p = 0.049). In our study clinical features like N and T status had a more important influence on survival rate. Nevertheless it appears that the immunohistological examination of PCNA in paraffin section could be a complementary prognostic tool for laryngeal carcinoma. PCNA expression may also be a valuable tool for differentiating malignant from benign laryngeal epithelium.

Ki-67 immunostaining and prognosis in laryngeal cancer.

The expression of the antigen defined by the Ki-67 antibody in paraffin sections from 154 biopsies of laryngeal squamous cell carcinomas was examined. There was a significant difference in Ki-67 expression between the control group and the patients with cancer (P < 0.001). There was no significant difference in the Ki-67 score between the patients with recurrence and the patients with a satisfactory outcome after treatment. There was no significant correlation between the Ki-67 score and the patient's age and sex, T and N stage and site of the tumour. The survival time of patients with a Ki-67 score > 30 was shorter than patients with a Ki-67 score < or = 30 but the difference did not reach statistical significance (P = 0.055). Multivariate analysis indicated that the only important prognostic factor was the existence of lymph node metastases. We could not confirm the value of Ki-67 as a prognostic factor in laryngeal cancer. Ki-67 score may assist in differentiating malignant from benign laryngeal epithelium.