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On the base of retrospective analysis of 927 cases of malignant neoplasms of the nose and paranasal sinuses, diagnosed and treated in 10 clinical centers in Poland from 1992-2001, the assessment of basic epidemiological data, including the localization of tumor, and stage of local and clinical advancement of the disease at the time of diagnosis has been conducted. In analyzed period of 10 years the trends to change the mentioned above parameters has been examined. The index of morbidity in this period was constant and compareable with figures published earlier. In the analyzed material there is a predominance of males and the sex ratio was 1.45. The majority of cases were between 50-69 years (55%). The most common histopathological diagnosis was carcinoma (58%). The majority of cases of malignant tumors of the nose and paranasal sinuses was diagnosed in the advanced stage T3-T4 (72.3%) with the highest percentage in the middle region. 90% of all cases were treated surgically, but in about 30% it was the only treatment (also in cases of stage T2-T4). In 56% of all patients the surgical procedure was completed by radiotherapy. This data suggest that indications for additional irradiation should be extended.

All cases of malignant tumours of the pharynx (excluding tumours of the tongue) were analyzed based on the retrospective data from the 5 clinical centers in Poland from the years 1992-2001. A considerable--over 50% increase in morbidity was found out regarding particularly tumours of the oropharynx. In the analyzed material there is a predominance of males (3:1) and the peak of morbidity significantly falls. The subjects with advanced tumours of the pharynx made 26% of the studied group. The most common histopathological diagnosis was squamous cell carcinoma and the most common site--the oropharynx, in particularly the tonsil. The data the center in Katowice, where tumours of the hypopharynx have been predominant in the last few years, may point a similar tendency in the other centers in the future.

A case of 74-year old woman with six separate cancers is presented. Four of them were nonmelanoma skin cancers (2 basal-cell carcinomas and 2 squamous-cell carcinomas), the remaining two were noncutaneous malignancies (invasive lobular carcinoma of the breast and squamous cell carcinoma of the parotid gland). Three lesions were present simultaneously on the head and neck region; basal-cell carcinoma on the cheek, squamous-cell carcinomas on the forehead, and in the parotid gland. All neoplasms were surgically removed, the region of affected parotid gland was additionally radiated. Extreme rarity of the multifocal primary malignancies is emphasized and the non-completely clear etiology, biology and pathology of these tumors is discussed.

A twenty-year scientific cooperation has been discussed (1979-1998) between four clinics for laryngology at Medical Universities in Cracow, Poznań, Warsaw and Lublin. The results of research concerning the epidemiology, diagnostics and treatment of the carcinoma of the larynx are presented.

The results concerning examination of DNA adducts in oral (23 patients), pharyngeal (23 patients) and larynx cancer (10 patients) subjects are presented. DNA adduct levels were compared in respect to anatomical structure (primary tumour location), number of cigarettes smoked, TNM stage, and age of patients. DNA was isolated from removed tissue (tumour and non-tumour surrounding tissue) using detergent/phenol extraction. 32P-postlabelling assay including nuclease P1-enhancement modification was applied. Aromatic DNA adducts were found in all studied tissues. Total DNA adduct levels (tumour and non-tumour tissues) was lowest in larynx cancer, higher in oral cancer and highest in pharyngeal cancer. There were no influence of age into formation of DNA adducts. The higher level of DNA adducts was found in tumour tissue of oral cancer in the group of smokers with metastasis into lymph nodes.

An exposure to tobacco smoke carcinogens is followed by an interaction of chemical carcinogens with DNA molecule resulted by the formation of carcinogen: DNA adducts. The study subjects were 40 oral and pharyngeal cancer patients with primary tumours diagnosed as squamous cell carcinoma. The biological samples purchased for analysis included tumour biopsy, the surrounding tissue (histopathologically recognised as non-malignant) and peripheral blood leucocytes. For DNA adducts analysis first DNA was isolated using phenol detergent extraction followed by 32P-postlabelling assay including P1 nuclease enhancement. Aromatic DNA adducts were found in all studied tissues. The average levels of DNA adducts in tumour and non-tumour tissues were found higher than in leucocytes. Biopsies from pharynx contained higher levels of DNA adducts than from oral cavities. Confounding effect of tobacco smoking and alcohol consumption on DNA adducts level was observed but it has not reached statistical significance. Formation of DNA adducts was not depended on such factors as patients age, sex, pulmonary tuberculosis, cancer progression (TNM), environmental pollution and mechanical irritation.

Carcinoma of unknown primary (CUP-syndrome) is taken into consideration when the patient has histologically confirmed metastases but the primary focus remains unknown or it's diagnosis is delayed. Metastases of unknown origin constitute from 5% to 31% of all neck metastases. Squamous cell carcinoma and anaplastic carcinoma metastases in the neck lymphatics suggest that location of primary focus can be found in head and neck region. Diagnostic procedures applied in detection of primary foci have been described. The knowledge of lymphatic metastases spreading routes is helpful in the primary focus detection. In the material of 1348 patients treated oncologically in the years 1991-1997 in ENT Department of Karol Marcinkowski University of Medical Sciences in Poznań, 22 were diagnosed for CUP syndrome. Primary foci were not found in 7 cases. In the remaining 15 patients the primary was located in nasopharynx, palatinal tonsil, tongue, hypopharynx, testes or breast. The treatment included the radical neck dissection with consecutive irradiation and/or chemotherapy, and in the case of diagnosing the primary one applied it's radical removal or radiotherapy.

Diagnostic possibilities in lethal midline granuloma (Wegener's granulomatosis, angiocentric lymphoma) based on the literature were presented. Results of diagnostic examinations in a case of 34 years old man admitted to the Dept. of Otolaryngology in Poznań were described.

Epidemiological studies have confirmed the correlation between tobacco smoking, environmental pollution and the incidence of cancers of the respiratory tract. The occurrence of laryngeal cancer in Poland is relatively high compared to other European countries. Since 1969 the mortality related to larynx cancer appears to be increasing. Tobacco smoke contains an abundance of such carcinogenic compounds as polycyclic aromatic hydrocarbons (PAH), aromatic amines and N-nitrosoamines, which can react with DNA and form adducts. We analyzed aromatic DNA adducts in laryngeal tissues from patients with primary laryngeal, which was confirmed histopathologically to be squamous cell carcinoma. The group consisted of 33 patients (5 women and 28 men). Total laryngectomy was performed in patients. A detergentphenol method was used for DNA isolation. Aromatic DNA adducts were analyzed by a 32P-postlabelling technique with butanol extraction and high performance liquid chromatography. The presence of aromatic DNA adducts was demonstrated in all tissues. Large interindividual differences of DNA adduct levels were seen in each tissue studied. There was a higher mean level of DNA adducts in interarytenoid area non-tumors (51.96/10(8) +/- 91.71 NN) than in non-tumor tissue elsewhere (46.91/10(8) +/- 46.36 NN) and tumor tissue (43.52/10(8) +/- 45.88 NN). Adduct levels were correlated with age, sex, cigarette smoking and TNM stage.

Comparative genomic hybridization was performed on 38 primary laryngeal carcinomas divided into two groups according to the metastatic phenotype. DNA copy number changes were detected in 22 of the 38 cases (57.9%). Gains were most frequently observed at 3q, 8q, and 9q, and losses were found in decreasing order at 18q, 3p, and 4. The mean value of losses was 2.5 times as high in metastasizing primary tumors (23/38) as in nonmetastasizing tumors. The most frequent losses in metastasizing tumors were at 18q, 3p, and 5q.

Tumours of head and neck belong to the most frequent types of cancer world-wide. In Poland, mortality from larynx cancer among males has been continuously increasing during the last decades up to 8.4 deaths per 100,000 men in 1993, which exceeds epidemiological records from other countries. The aetiology of laryngeal cancer is strongly associated with exposure to carcinogens present in tobacco smoke. The review describes a sequence of molecular and cellular events from carcinogenic exposure, DNA adduct formation, detection of mutations in the p53 gene, loss of heterozygosity (LOH) in chromosomal loci encoding the p53 and p16 genes, and loss of control of the cell cycle. The section concerning DNA adducts includes a discussion of the role of such confounders as exogenous exposure, the age and sex of the subject, and disease progression. The significance of genetic factors as individual risk determinants is discussed in relation to bleomycin-induced chromosome instability and in connection with the occurrence of defects in genes encoding detoxifying enzymes. The question concerning the substantial difference between men and women in larynx cancer morbidity and mortality remains open, even when the significantly higher adduct formation in male DNA compared with female material was taken into account. Preliminary experiments suggest a role of the frequently observed loss of the Y-chromosome.

The difficult and complicated mechanism of cancer development with little knowledge about the biology of existing cancers can lead to a permanent search for new examination techniques to improve the precision of life expectancy in patients and the selection of the most efficient methods of treatment. The aim of this study was to analyze certain prognostic factors, i.e., p53, Ki67, proliferating cell nuclear antigen (PCNA), DNA ploidy and cell proliferating activity, as well as the degree of morphological differentiation and cell maturity evaluated on an ultrastructural level in patients with laryngeal cancers in connection with data obtained from follow-up examinations and the clinical course of the disease. Neoplastic tissue was taken from 120 patients with laryngeal cancers. All underwent surgical treatment, radiotherapy and combined treatment in the Department of Otolaryngology. Karol Marcinkowski University School of Medical Sciences, Poznań, Poland, and the Department of Otolaryngology-Head and Neck Surgery, Haukeland University, Bergen, Norway. Before beginning treatment all patients underwent histological verification of their neoplastic tissues. Histopathological examination proved that the majority of cases (95%) had a squamous cell carcinoma. The occurrence of changes within the lymph nodes of the neck (N) was significantly correlated with T, S, Ki67, metastases to lymph nodes, DNA ploidy, site and surgery performed. The degree of clinical progression (S) was intercorrelated with T, N, p53, Ki67, PCNA, DNA ploidy, site and laryngectomy. The occurrence of oncoprotein p53 in neoplastic cells was measured by the staining degree of their nuclei and was correlated with T, S, DNA ploidy, metastases to lymph nodes, PCNA and site. The degree of staining of neoplastic cells for the nuclear antigen Ki67 was correlated to T, N, G, S, DNA ploidy, metastases to lymph nodes and surgical treatment. The proliferative antigen PCNA in the examined population of patients was intercorrelated with T, p53, Ki67, metastases to lymph nodes and surgical treatment. The results obtained from DNA flow cytometry could be associated with N, G, p53, Ki67 and metastases to lymph nodes. On the basis of the results obtained, the techniques suggested for the morphological and biological evaluation of neoplastic cells in cancer of the larynx should include TNM classification + G + DNA + p53 + Ki67.

The span of time between the appearance of the first symptoms of larynx cancer and the moment it is diagnosed in Poland amounts to approximately 6 months. It is the result primarily of the fact that patients tend to consult a doctor late after the symptoms show as they underestimate them due to their lack of knowledge concerning their nature. In some cases the diagnosis may be difficult to give even for a specialist. The paper presents the cases of three patients with an unusual course of larynx cancer.

The main purpose of this study was subjective and objective evaluation of voice function before and after extended frontolateral laryngectomy, followed by reconstruction with a mucochondrial graft from the nose. The next aim of this study was analysis of phoniatric and acoustic results depending on: (1) the extent and localization of the neoplastic process; (2) the wound-healing process (including the time of decannulation and effective deglutition); (3) the substitute mechanism of phonation. In all, 40 patients (37 men and 3 women) having T1B (67.5%) and T2 (32.5%) glottic cancers were examined before and after the operation. The ENT investigation included each patient's history from the beginning of illness, a subjective evaluation of the voice by patients before and after the operation, determination of laryngeal mobility of the larynx and indirect laryngoscopy during phonation. Phoniatric examination included voice recordings, average voice pitch, voice range, maximum phonation time, microlaryngoscopy and microstroboscopy. Acoustic analysis covered the harmonic structure of the voice, jitter, shimmer, noise components and basic frequency. Results showed that the extent of the neoplastic process before operation did not affect essential voice quality after operation in stage T1B and T2 disease. The maximum phonation time was shortened in T1B patients from 16.5 s to 9.28 s and in T2 from 16.7 s to 9.8 s. The average voice pitch was decreased in T1B from 177.3 Hz to 111.74 Hz and in T2 from 163.8 to 99 Hz. A correlation between acoustic analysis and phoniatric examinations was found. The value of the first formant decreased by 15.1 Hz, jitter increased 2%, shimmer increased 0.9 dB and basic frequency decreased. The voice quality after operation showed a statistically significant dependence on the mechanism of phonation. The best results were found in patients in whom phonation was the result of removing the vocal fold and postoperative scar vibration. The worst results were found in those patients with a sphincter mechanism of phonation.

According to epidemiological data concerning laryngeal cancer there is almost ninefold higher morbidity in male population than in females. The aim of this study was to analyse on molecular level the genotoxic effects arising under the same exposure to tobacco smoke in males and females. In biopsies received from laryngectomy material we determined levels of aromatic and alkylated DNA adducts in tumours and in adjacent non-tumour tissue. It was established that levels of DNA adducts found in male DNA samples exceeded those in female DNA samples 1.5-3.8 times, which was recognised as a molecular evidence for epidemiological differences. Next, testosterone and sex hormones binding globulin (SHBG) were determined in male subjects blood serum. The levels of testosterone and SHBG very weakly correlated with DNA adduct levels even when subjects were separated into age groups. It is concluded that levels of testosterone and SHBG are not the proper markers of individual susceptibility to genotoxicity of tobacco smoke carcinogens.

An inter-individual variability in sensitivity to mutagen-induced genotoxicity was studied in respect to an estimation of larynx cancer risk. Bleomycin induced chromosome breaks were analysed in blood lymphocytes proliferating in vitro in a group of 35 larynx cancer subjects and in 18 healthy controls. A significantly higher index of chromosome breaks was found in larynx cancer subjects as compared with the controls. The distribution of individual results indicates that subjects oversensitive to bleomycine were identified only among laryngeal tumour patients. A potential usage of bleomycin test in tumour prognosis is discussed.

In a group of 42 patients with surgically treated laryngeal carcinoma, who were divided into those before their 50 and after 60 years of age, main lymphocyte subsets of peripheral blood lymphocytes were assessed by means of flow cytometry. In the group after 60 years of age significantly increased percentage and raised total number of NK (natural killer) cells were found. In the whole group increased total number of all lymphocyte subsets was found. These data indicate that older patients despite an increased number of total to lymphocytes NK cells show higher percentage and total number as compared with normal population at that age.

A case of squamous cell carcinoma of the nose and paranasal sinuses in an 18-year-old male is presented. Carcinoma of the nose and sinuses is not common and accounts for 3-5% of an all malignancies in the head and neck. Peak incidence of the disease seems to occur in the 6th and 7th decade of life. No cases of nasal carcinoma were observed under the age of thirty. The authors discuss the difficulties in setting the diagnosis--nonspecific symptoms mimic those of chronic sinusitis.

A study of DNA ploidy was carried out including 84 cases of laryngeal squamous cell carcinoma. Material was fixed during 30 min in 3% paraformaldehyde and embedded in low-melting-point paraffin. The histologic studies were done for diagnosis and general view. Results were as follows. The highest percentage of cancers with DNA diploidy was found in well- and medium-differentiated tumors. Among well-differentiated carcinomas there were 18% diploid versus 5% polyploid tumors. In the medium-differentiated cancers there were 23.5% diploid, 6% polyploid, and 6% hyperdiploid tumors. The highest percentage of DNA hyperdiploidy and poliploido-aneuploidy was found in low-differentiated cancers. Additionally, tumor proliferative activity was evaluated in relation to the percentage of cells in phase S of cellular cycle. Special attention was paid to tumors which revealed the phenomenon of DNA poliploidy-aneuploidy beside DNA diploidy.

The analysis of survival of 311 patients after total laryngectomy due to cancer and conventional postoperative radiotherapy was performed. During irradiation in a part of patients were introduced interruptions in treatment and no related diseases. The gap in treatment was taken in account and for this factor all patients were divided into 3 groups; without gap in treatment (A), with short gap--below 7 days (B) and with long gap--over 7 days (C). All groups were comparable. It was concluded that the long gaps increase the failure in treatment for about 30%.

The p53 gene is known as an anti-oncogene that manifests its function by controlling the cell cycle and is responsible for apoptosis of cells with unrepaired DNA. An accelerated p53 protein synthesis is the first response of a cell following DNA damage. However, mutations of the p53 gene can disturb protein synthesis or may be responsible for synthesis of a changed protein unable to control the cell cycle. Laryngeal tissue specimens from 120 patients were tested by immunohistopathological staining to detect mutated wild-type p53 protein. It was found that p53-positive specimens correlated with TNM staging and histopathological grading. Another indication of entering the cell cycle and undertaking an active proliferation by laryngeal cells was shown by detection of proliferating cell nuclear antigen (PCNA) and Ki67 nuclear antigen, which appeared in proliferating cells (late G1, S-G2 and M phase), but was absent in resting cells. Scoring of the staining for p53 protein, PCNA and Ki67 correlated with each other. DNA from 40 specimens was then isolated, amplified by polymerase chain reaction and analysed by single-strand conformation polymorphism and DNA sequencing for mutation in the p53 gene. Fifteen DNA samples were found to be positive, while mutations were detected in exons 5-8 in 13 samples. The majority of mutations were found in tissue specimens from T3 and T4 tumors. A possible explanation is almost half was attributable to genotoxic effects of tobacco smoking. Changes in the p53 gene and its products may also reflect early changes in laryngeal carcinogenesis and be of prognostic value.

In a group of 60 patients with surgically treated laryngeal carcinoma blood lymphocyte subsets were assessed on the day of surgery (day 0) and six weeks thereafter by means of flow cytometry. Blood cells at day 0 were also compared to tumor infiltrating lymphocytes (TIL) isolated from surgical specimens. Significant alterations were found in postoperative period as compared to day 0 manifested by the fall of B cells, increase of activated T lymphocytes and NK cells. There were also marked changes between blood cells at day 0 and TIL, evidence in rise of B cells, of activated T lymphocytes and decline of NK cells within the latter. These data suggest that the assessment of lymphocyte subsets may be of value in immunological monitoring of laryngeal carcinoma patients.

A rare case of carcinoma cuniculatum of the nasal cavity et paranasales sinuses is presented. This tumor is mature planoepithelial carcinoma, difficult to diagnose even by experienced histopathologists. It is characterized by very slow growth and local malignancy, develops it damages cartilages and bones.

Genotoxical agents as PAH, nitrosamines, aromatic amines located in tobacco smoke are responsible for disorders of structure and function of DNA chromosomes, proteins and also initiation of carcinogenesis. DNA adducts are recognized as measure of the biological effective dose of exposure to environmental genotoxicant. So far most studies on DNA adducts after human exposure to tobacco smoke have ben carried out on white blood cells, lungs and oral cavities tissue. The aim of this work was estimation of relationship between state of neoplastic disease (TNM system) and number of aromatic DNA adducts. The subject were 37 patients with primary larynx tumor. In every case histopathological investigation revealed squamous cell carcinoma. There were 33 total and 4 partial laryngectomies performed. From tumour and nontumour larynx tissue DNA was isolated. Analysis of DNA adducts was performed by the 32P-postlabelling method. The results were characterized by individual differentiation. The highest level of DNA adducts was found in larynx tumour cells. In case of strong smokers (30-40 cigarettes per day) the level of aromatic adducts was higher then in non- or ex-smokers. In both tissues (tumour and non-tumour) the highest level of aromatic adducts was in T3 stage, the lowes in cause of T2 stage. In tissues with T4 stage the level of DNA adducts was intermediate. One has been observed decrease tendency in level of DNA adducts which is connected with increase of TNM stage.

Among host lymphoid cells engaged in anti-tumor defence, tumor infiltrating cells (TIC) are apparently the most suitable for this purpose, due to feasibility of direct contact with tumor cells. The aim of the present study was to evaluate distribution of TIC which express phenotype of cytotoxic cells, in tissues of laryngeal carcinoma. Cryostat sections of surgical tumor samples were subjected to sensitive APAAP immunohistochemistry, following reaction with one of the panel of monoclonal antibodies (MoAbs) vs. several CD antigens and assessed semiquantitatively. It has been found that the content and distribution of potentially cytotoxic cells are quite heterogenous and vary from case to case in examined cancer. CD8+ cells and those bearing NK cell phenotype were the most frequently encountered, mainly within tumor mass. The cells belonging to NK cell subsets, detected by GL183 and EB6 MoAbs could be demonstrated in tumor proximity. TCR-1+ (tau/delta) T lymphocytes were quite a few in part cases. On the other hand, only a scarce number of cells among TIC expressed interleukin-2 receptor. It is concluded that in the vicinity of laryngeal cancer there are fairly large numbers of potentially cytotoxic cells, but at low or nil state of activation.

Serum and tissue zinc concentrations in 30 subjects with operable squamous cell carcinoma of the larynx, aged 36-56 were determined by atomic absorption spectrophotometry. The concentration of this cation in cancerous tissues and in unchanged homologous tissues do not differ significantly. Mean zinc serum level was lower before treatment.

Mononuclear host cells isolated from primary laryngeal carcinoma were assessed by means of indirect immunofluorescence with a panel of monoclonal antibodies against various lymphocyte subsets and macrophages. Tumours of various staging groups were examined in parallel with cells isolated from patient and donor peripheral blood (PBL). It was found that percentage values of cells bearing T3 and T4 phenotype were reduced both in tumour infiltrating cells (TIC) and in PBL population. The fall in T4+ cells in PBL from cancer patients in T3 and T4 staging groups was statistically significant (p less than 0.01) as compared with donor cells. Corresponding values for T8+ cells from TIC were increased in T1 and T2 staging groups of cancer, but showed a gradual fall in advanced stages. The T4+/T8+ cell ratio was decreased in both TIC and PBL cells. The HNK-1+ (NK) cell pattern in TIC was analogous to that for T8+ cells, i.e. the cell percentage decreased with advance in tumour growth. Corresponding values for OKM-1+ were increased in TIC and in patient blood, though in TIC they grew in proportion to tumour growth. Ia+ (HLA-DR+) cells in peripheral blood were significantly increased in patients versus those of donors (p less than 0.01), but only in T3 and T4 staging groups of examined cancer. These results show that subsets of tumour infiltrating cells in laryngeal carcinoma are a complex phenomenon, associated with growth and progression of tumour.

The content of magnesium in tissues, erythrocytes and serum was analysed by atomic absorption spectrometry. A higher concentration of magnesium was found in malignant laryngeal tissue and in lymph nodes of the neck compared to homologous pre-cancerous tissue. In pre-cancerous lesions of the larynx the magnesium concentration of the erythrocytes and serum lay at the lower limit of normal. In patients with cancer of the larynx, the magnesium concentration was considerably below the normal levels and continued to decline as the disease progressed.

In 100 cases with different stages of planoepithelial laryngeal cancer and in 13 precancerous changes the urine magnesium levels were examined two times by means of absorptive spectrometry before surgery and half a year after. In precancerous period group (I stage according to WHO) no differences were found in comparison to the control group. As the disease progressed the urine magnesium level deteriorated according to the cancer stages. In IV stage the level was the lowest (P less than 0.01). The normalization of the urine magnesium level was found in some cases 6 months after surgery and radiotherapy.

In order to gain some insight into host cell accumulations within primary tumour, frozen sections from surgical specimens of laryngeal carcinoma were subjected to indirect immunofluorescence using a panel of monoclonal antibodies against various human lymphocyte subsets as well as macrophages. In addition, polyclonal antibodies against Ig were used in order to trace B cells. Numerous host cell infiltrates seen at the tumour periphery were composed of T4 (helper) lymphocytes and macrophages. Lymphocytes of OKT8 (suppressor/cytotoxic) and Leu-7 (NK cells) series were intermingled with tumour cells in the case of scanty infiltrates. Infiltrating cells were also linked to the presence of metastases in regional lymph nodes. OKT4-positive abundant infiltrates were usually accompanied by uninvolved nodes, while scanty ones with OKT8 specificity were relatively frequently seen in the patients with evidence of nodal metastases. These differences were not statistically significant, however, B cells as well as plasma cells were infrequently observed and were encountered both in tumour samples with intensive cellular infiltrates as well as in those with scanty ones.