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SUMMARY: OBJECTIVES/HYPOTHESIS The main objective of this study was to investigate the effect of the administration of a novel immunoadjuvant, leukocyte interleukin injection, as part of an immuno-augmenting treatment regimen on the peritumoral and intratumoral subpopulations of the tumor infiltrating mononuclear cells and on the epithelial and stromal components, when administered to patients with advanced primary oral squamous cell carcinoma classified as T2-3N0-2M0, as compared with disease-matched control patients (not treated with leukocyte interleukin injection).STUDY DESIGN Multicenter Phase I/II clinical trial. Fifty-four patients from four clinical centers were included in the dose-escalating study (27 in each group [leukocyte interleukin injection-treated and control groups]). Cumulative leukocyte inter-leukin injection doses were 2400, 4800, and 8000 IU (as interleukin-2 equivalent).METHODS Paraffin-embedded tumor samples obtained at surgical resection of the residual tumor (between days 21 and 28 after treatment initiation) were used. Histological analysis, necrosis evaluation, and American Joint Committee on Cancer grading were performed from H&E-stained sections. Immunohistochemical analysis was performed on three different tumor regions (surface, zone 1; center, zone 2; and tumor-stroma interface, zone 3). Trichrome staining was used to evaluate connective tissue, and morphometric measurements were made using ImagePro analysis software. Cell cycling was determined by the use of Ki-67 marker.RESULTS Leukocyte interleukin injection treatment induced a shift from stromal infiltrating T cells toward intraepithelial T cells and posted a significant (P < .05) increase in intraepithelial CD3-positive T cells independent of the leukocyte interleukin injection dose, whereas the increase in CD25 (interleukin-2 receptor alpha [IL-2Rα])-positive lymphoid cells was significant only at the lowest leukocyte interleukin injection dose (P < .05). Furthermore, both low- and medium-dose leukocyte interleukin injection treatment induced a significant (P < .05) increase in the number of cycling tumor cells, as compared with control values.CONCLUSION The results could be highly beneficial for patients with oral squamous cell carcinoma. First, leukocyte interleukin injection treatment induces T-cell migration into cancer nests and, second, noncycling cancer cells may enter cell cycling on administration of leukocyte interleukin injection. This latter effect may modulate the susceptibility of cancer cells to radiation therapy and chemotherapy. The findings may indicate a need to re-evaluate the way in which follow-up treatment (with radiation therapy and chemotherapy) of patients with head and neck cancer is currently approached. [ABSTRACT FROM AUTHOR]

PET-CT examination was conducted with 440 patients treated at the Department of Head and Neck Surgery, National Institute of Oncology, Budapest, between January 1, 2006 and December 31, 2010. Out of them 77 patients were selected with whom no examination of any sort (physical, pan-endoscopy, or any of the conventional imaging techniques) succeeded in identifying the primary tumour. In each case the primary examination (aspiration cytology and histology) verified cervical metastases, most of them being squamous cell carcinoma. The significance of PET-CT was retrospectively evaluated in cases of unknown primary tumour with verified cervical metastases. We tested the sensitivity of PET-CT in detection of the primary malignant tumour, and possible distant metastases or a second primary in order to plan an optimal treatment schedule for the patient. Patients with whom the examinations specified in the treatment protocol (physical examination, pan-endoscopy, conventional imaging, biopsy) had failed to diagnose the primary tumour were referred to PET-CT. In each case 18F-FDG tracer was used. In 21/77 patients (27%), the PET-CT yielded unequivocal evidence for the primary tumour confirmed by histology, as well. With 10 others (13%), the precarious diagnoses by various imaging techniques were confirmed by the PET-CT. False positive findings with PET-CT that were not verified either by histology or control examination tests occurred but in 10 patients (13%). Concerning the primary tumour, false negative result was obtained only with 3 patients (4%). It should be noted that their retrospective evaluation proved diagnostic errors, the primary tumours were visible in all the scans. With 33 patients (43%) PET-CT furnished no additional information compared to the previous examinations. In 10 patients, asymptomatic distant metastases and in 3 patients synchronous tumours were diagnosed. We also acknowledge that the significance of PET-CT using 18F-FDG is unquestionable in the detection of unknown primary tumours. It is strongly recommended to re-include the detection of unknown primaries in the approved national indication list of PET-CT. (Note, until January 1, 2008 it had been included!) PET-CT is capable of detecting a primary tumour, after all unsuccessful diagnostic examinations till then, in 25-40% of the cases. One cannot disregard the role and significance of PET-CT in the detection of asymptomatic synchronous tumours, or distant metastases. These benefits make PET-CT a suitable tool for the refinement of individually tailored treatment strategies leading to better therapeutic results and more favourable cost-benefit ratio.

Squamous cell cancer of the head and neck (SCCHN) is the third most common cause of death from cancer among Hungarian males. This cancer is caused in most of the cases by chronic toxic effects of the environment, especially by tobacco smoking and regular alcohol consumption. SCCHNs similar for the first sight, might have different clinical course, mainly because of their different responses to anticancer therapies. In this study, potential biomarkers were examined that were thought to develop as biologic responses to the known environmental toxicities, therefore, their testing is supposed to help answer the most important questions of clinical oncology: understanding tumor development, early detection of cancer and individually tailored therapy planning based on the biological nature of a particular cancer. Elevated rate of spontaneous chromosome aberrations proved to be a reliable marker of the SCCHN phenotype. However, increased mutagen sensitivity by the bleomycin-test, unlike in the US or in Western Europe, was not suitable to detect the individual cancer risk in this country, because of the high mutagen sensitivity of more than half of the healthy Hungarian population examined. In the light of the high cancer incidence and mortality statistics of Hungary, the frequency of elevated mutagen sensitivity even among healthy people is a meaningful finding, and requires further clarification. Our studies on the hormonal status of male SCCHN patients revealed some pathological changes in the sex steroid and pituitary hormone serum levels, which most probably accompanied chronic alcoholic liver disease. The elevated prolactin and decreased total and free testosterone levels predicted poor prognosis of the disease. The importance of the potential relationship between hormones and SCCHN is underscored by our further finding of functioning estrogen and progesterone receptors in SCCHN tissue of our patients.

In Hungary the number of oral and pharyngeal cancers is alarmingly high. While the mortality rate in 1955 was 282, by 2005 it rose to 1567. However, in the last 1-2 years stagnation can be observed. Nevertheless, even now significant proportions of men and women are involved. Alcohol consumption and smoking are invariably the leading causes, but one cannot disregard the shortcomings of oral cancer screenings, either. Unfortunately, drastic changes in this field are not likely to occur in the near future. Numerous solutions have been developed for the replacement of soft tissue. In our article, we describe and evaluate four of them. When using these techniques, we were often successful in replacing soft tissue deficiencies.

The aim of treating head and neck cancer is to eliminate the tumor and save functions as much as possible. Despite all efforts the vital (swallowing) and communicative (phonation, articulation) functions can be injured. The treatment of dysphagia is the most important in the rehabilitation, because it can lead to fatal complications: aspiration pneumonia (for example aspiration of saliva), dehydration, malnutrition. According to the localization of the lesion we distinguish oropharyngeal and esophageal dysphagia. The aspiration may be pre-, intra- and post-deglutition. The aspiration without coughing is called silent aspiration which is mainly seen in neurogenic dysphagia, but can also happen in head and neck cancer patients. There are different possibilities to compensate the failing functions in the phoniatric rehabilitation. The swallowing therapy includes causal, compensatory and dietary strategies. In addition to the swallowing therapy the treatment of communicative dysfunctions with articulation exercises will also improve the quality of life of the patients.

Oral cancer incidence in Hungary is strikingly high, even by international standards. In most cases the tumours are to be treated in advanced stage. Hence it follows that we are often forced to remove a part of the mandible, too. We usually use a fibula free flap to reconstruct the bone deficiency. In this paper we report on our clinical experience with fibula free flap.

Applicability of alcohol- and smoking-related cancer-risk biomarkers might be modified by several factors. Among those, reality of self-reports on alcohol consumption of alcoholic patients with different diseases and extreme high mutagen hypersensitivity of Hungarians, as well as the immunologic role of peripheral lymphocytes as experimental objects of cytogenetic biomarkers seem to be new viewpoints of interest. To clarify these problems, 432 head and neck cancer patients (HNCP), 62 alcoholics with alcoholic hepatitis (ALCL), and 101 disease-free chronic alcoholics (ALC) were examined. Despite clinically confirmed alcohol-related diagnoses (and GGT and MCV values) only about half of HNCPs and ALCLs reported about any alcohol consumption, in contrast to the realistic self-reports of ALCs. In cytogenetic case control investigations no difference between the spontaneous rate of chromosomal aberrations (CAs) of healthy controls and ALCs was found, however, genetic instability expressed as a 40-50% elevation rate of CAs in HNCPs and ALCLs might be associated with systemic inflammatory reaction of lymphocytes. Bleomycin sensitivity assay showed the highest break/cell (b/c) values not in HNCPs (1.06 b/c) as it was reported earlier, but in "healthy" ALCs (1.52 b/c). This phenomenon can be related to the local effect of genotoxins (alcohol, smoking, and in particular the diet), which probably reflects merely a reaction of mucosal immune system. Nearly 50% of mutagen-hypersensitive Hungarian controls, in contrary to the expected 10-20% ones, might also be explained by this. Similarly, HNCPs with oral cancer, where the local mutagen effect was the most intensive, had the highest b/c values. In conclusion, when cytogenetic biomarkers of alcoholism are examined, the subjective character of self-reports at epidemiologic level and immunologic role of lymphocyte subpopulations as genetic confounders must also be taken into consideration.

In spite of the continued expansion of non-surgical therapeutic modalities surgery still plays an important role in the treatment of head and neck cancer. Parallel with the use of conventional approaches, more sophisticated surgical approaches, like the use of laser in oncologic surgery, appeared with a more favorable outcome. Laser is a precise surgical tool, particularly when coupled to an operating microscope (with a variable spot size micromanipulator), allowing microprecision and hemostatic ability. The benefits of the use of laser are: bloodless operation field, high hit probability, "no touch" technique, ablasticity, support of tissue repair, and the lack of edema and scar formation. Between 1981 and 2008, 7934 surgical procedures were performed at the Department of Head and Neck Surgery, National Institute of Oncology, Budapest, Hungary. The aim is to present our results and experience with laser surgery of cutaneous lesions of the head and neck, oral, pharyngeal and laryngeal pathologies including cases of laryngotracheal stenosis.

Retinoids as important growth and differentiation regulating agents have a potential role in the chemoprevention of head and neck squamous cell carcinoma (HNSCC). Despite the promising preclinical and early clinical findings, limitations of application are raised by intrinsic resistance acquired during carcinogenesis. Retinoic acid receptor beta2 (RAR beta2) is one of the proximate mediators of retinoid signalling and its expression is often diminished in early stages of head and neck carcinogenesis. One form of retinoid resistance has been associated with the methylation-induced silencing of the RAR beta gene. We studied primary HNSCC samples of different anatomical sites in respect of methylation, expression and allelic loss of RAR beta gene. A strong correlation (p<0.01) was found between hyper-methylation and reduced expression of RAR beta2, however the allelic loss at 3p24, the locus of RAR beta, did not considerably influence its mRNA level. Hypopharynx tumors showed significantly lower hypermethylation (p<0.05) and higher mRNA expression levels of RAR beta2 compared to the tumors located at other sites of the head and neck. We could also provide evidence that poorly differentiated grade 3 tumors had significantly higher RAR beta2 expression and lower methylation levels (p<0.05) than better differentiated grade 1 and grade 2 tumors. In addition, we found a good correlation between the methylation degree of the RAR beta2 promoter and the ages of patients. Collectively, our results suggest that evaluation of several factors such as tumor location, age, histology and methylation state of the RAR beta gene might contribute to the selection of patients for retinoid-based chemoprevention.

The aims of this study were to assess the sex hormone receptor status of head and neck (HNC) cancers. Frozen surgical samples (n = 67) of HNC patients were analyzed. Protein expression of estrogen receptor (ER)alpha, ERbeta and progesterone receptor (PgR) of tumor cells was determined by immunocytochemistry. Data were confirmed at mRNA level by nested-PCR and sequencing. ER and PgR expressions confirmed by PCR analysis were frequent in HNC: 50.7 and 49.3% respectively. Concerning the ER isoforms, ERalpha expression was predominant over ERbeta in both of oral cavity- as well as laryngeal/hypopharyngeal (LH) cancers. The delta3 splice variant of ERalpha was detected at low frequency, while the delta5 splice variant of ERbeta was frequent in HNC. The incidence of functional receptor expression (coexpression of ER and PgR) was relatively frequent also in HNC (27/67, 40.3%) which was independent of the anatomical location of the tumor. Sex hormone receptor expressions did not affect survival of HNC patients, however, in the LH cancer subgroup ER expression was associated with a trend of shortened survival (p = 0.0636, Mantel-Cox generalized savage). ERalpha,beta and PgR expressions are frequent in HNC and may affect the prognosis of the disease, at least in case of LH cancers.

Head and neck squamous cell carcinoma (HNSCC) develops in at least 80% of cases in men with a history of smoking and heavy alcohol consumption, still it is only diagnosed in a small proportion of alcoholics. Endocrine milieu is an important factor in carcinogenesis and prognosis of several cancer types. The aim of our study was to investigate sex steroid and hypophyseal hormone status of male HNSCC patients in comparison to healthy volunteers and to patients with alcoholic liver disease, to determine possible hormonal alterations characteristic of cancer. Liver function (GGT level), and serum levels of gonadotropic hormones (FSH, LH, prolactin), sex steroids (estradiol, progesterone, testosterone) and sex hormone-binding globulin (SHBG) were compared in 130 male HNSCC patients, 54 patients with alcoholic liver disease but no known cancer, and 56 healthy controls. We found abnormal values of liver function in both HNSCC patients and alcoholics compared to healthy controls, suggesting the presence of alcoholic liver disease in the former group as well. On the other hand, a significant elevation in the level of DHEA, FSH and LH was observed in cancer patients exclusively. As a conclusion, abnormal alterations in sex steroid hormone levels can frequently be found in HNSCC patients, which may be caused in part by the alcoholic liver damage accompanying the disease. The significant increase in FSH and LH serum levels, observed only in the cancer patients, indicates that these hormones may play a role in the development and/or progression of HNSCC.

Purpose: To evaluate the predictive value of intratumoral microvessel density (MVD) in patients with locally advanced, primarily inoperable oropharyngeal cancer (OPCC) treated with irradiation alone., Patients and Methods: Tumor samples of 35 patients with OPCC subjected to radiotherapy were taken before and after 20 Gy irradiation. Histological grade, mitotic activity index and MVD of OPCC were determined. Correlations with response and survival were analyzed., Results: Stage and posttreatment MVD decrease showed significant correlation with objective response. Postirradiation MVD decrease correlated significantly with response to irradiation and overall survival, and a trend could be seen for progression-free survival., Conclusion: This study has shown that the change in MVD after irradiation can be an indicator of the success of radiotherapy in locally advanced OPCC, and may serve as a predictive factor thus helping to select patients who could benefit from more aggressive treatment.

In the aetiology of head and neck squamous cell carcinoma (HNSCC), smoking and heavy alcohol consumption are the main environmental risk factors. The bleomycin (BLM) sensitivity assay is believed to measure environment-related cancer risks, mainly of HNSCC. Previously, we have shown that this method is only moderately sensitive to identify individuals at high risk for developing HNSCC, due to broad overlap of BLM-induced chromatid breaks per cell (b/c) between cancer patients and controls, and alcoholics with liver diseases. In the present study, we evaluated whether the differences between patients and controls are more manifested when the risks according to localization of HNSCC are examined. BLM sensitivity in lymphocytes of 278 patients with HNSCC at four different anatomical sites, and that of 356 frequency-matched controls was studied. There was a significant difference in BLM-induced b/c values between patients (1.11 b/c) and controls (0.97 b/c); however, considering all HNSCC cases, only 58.3% of patients and 43.3% of controls were mutagen sensitive. When the patients were distributed according to tumour sites, mutagen sensitivity of those with cancer of oral cavity, oropharynx and hypopharynx was significantly higher than that of the frequency-matched controls (1.12-1.14 b/c versus 1.00 b/c), while laryngeal tumour patients (1.05 b/c) did not differ from controls (1.00 b/c). When the associations between BLM sensitivity and the risk of HNSCC sites were examined, it was expressed mostly in patients with tumours of the oral cavity and oropharynx (OR = 1.97 and OR = 1.90), and not in patients with tumours of the hypopharynx and larynx. Though the mutagen sensitivity decreased from the oral cavity down to the larynx, indicating that the site-specific risks may differ, the BLM assay shows weak and controversial associations between mutagen sensitivity and cancer risk of patients even at specific HNSCC sites.

Purpose: To investigate the clinicopathologic effects of local neoadjuvant Leukocyte Interleukin Injection (LI) regimen in oral squamous cell carcinoma (OSCC) patients. Treatment regimen included LI 800 IU/d as interleukin-2 (IL-2), administered half peritumorally and half perilymphatically five times per week for 3 weeks; low-dose cyclophosphamide; indomethacin; zinc; and multivitamins., Patients and Methods: Thirty-nine patients diagnosed with T2-3N0-2M0 OSCC participated in the pathology portion of this phase II multicenter study (19 LI-treated patients and 20 historical controls). Clinical responses were determined by imaging. Paraffin-embedded tumor samples were obtained at surgery for all patients. Surgery for the LI-treated group was performed between days 14 and 54 after the end of treatment. Histologic evaluation, pathologic staging, necrosis, and American Joint Committee on Cancer grading were performed from hematoxylin and eosin sections. Immunohistochemistry and morphometry determined cellular infiltrate., Results: Two pathologically complete, two major (> 50%), and four minor responses (> 30% but < 50%) resulted from LI treatment (overall response rate, 42%). Histopathology showed that the intratumoral CD4+:CD8+ ratio was low (< 1) in patients not treated with LI (controls). An increase in tumor-infiltrating CD4+ and a decrease of CD8+ T cells was observed in LI-treated patients, leading to a significantly (P < .05) higher intratumoral CD4+:CD8+ ratio (> 2.5). This was paralleled by dendritic cell transition from tumor surface toward stromal interface (P < .05), with macrophage decrease and neutrophil accumulation, multifocal microscopic necrosis, and significant (P < .05) increase in tumor stroma of LI-treated patients compared with controls., Conclusion: LI-treated OSCC patients were characterized by a markedly altered composition of tumor-infiltrating mononuclear cells, increased CD4+:CD8+ ratio, and increased tumor stroma to epithelial ratio, all of which were distinct from controls.

Squamous cell cancer in the head and neck region (HNSC) is unique concerning its progression since it remains locoregional for long time and visceral metastases develop only in a later stage of the disease. Accordingly, molecular markers of the local invasion and the lymphatic dissemination both have critical importance. HNSC progression is associated with deregulated control of cell proliferation and apoptosis but it seems equally significant the disregulation of the proteolytic machineries. Here we outline the lymphatic metastatic cascade for HNSC to depict key molecular determinants as possible prognostic factors or therapeutic targets identifying immunological selection as a major feature. Unlike in local spreading, invasive potential of cancer cells seems to be less significant during lymphatic dissemination due to the anatomical properties of the lymphatic vessels and tissues. There is a general believe that HNSC is one disease however, data indicate that the anatomical localization of the tumor (the "soil") such as oral, lingual, glottic or pharyngeal has a significant effect on the gene expression profile and corresponding biological behavior of HNSC. Furthermore, even the endocrine milieu of the host was proved to be influential in modulating the progression of HNSC. Gene expression profiling techniques combined with proteomics could help to define and select usefull genetic and biomarkers of progression of HNSC, some of them could well be potential novel therapeutic target.

In this prospective study we have evaluated the predictive role of intratumoral microvessel density (MVD) for the therapeutic response and progression of inoperable oropharyngeal cancer (OPCC) treated with radiotherapy. Thirty-five OPCC patients were enrolled in this study. Biopsies from the primary tumor were taken before and after 20 Gy irradiation. Pathological factors such as histological grade, mitotic activity index and MVD were determined in both samples. Correlations of these factors with response to therapy, progression-free and overall survival were analyzed after a follow-up period of a minimum of 50 months. Objective response and survival was independent of the pretreatment MVD of OPCC. On the other hand, objective response was significantly affected by stage and low posttreatment MVD. Response to irradiation, and therapy-induced low postirradiation MVD were significant indicators of better overall and progression-free survival. We have shown in this small exploratory study that the anti-angiogenic effect of irradiation has a predictive value of the success of radiotherapy in locally advanced OPCC and can be used to select a radioresistant patient population which might require a more aggressive protocol.

Background and Purpose: . To date none of the studies examined the feasibility and efficacy of interstitial high-dose-rate (HDR) brachytherapy in the treatment of carcinoma of the tongue base. Therefore the aim of this study was to contribute to this issue., Patients and Methods: . Between 1992 and 2000 37 patients (mean age 55 years) with T1-4 and N0-3 carcinoma of the base of tongue were presented. Neck dissection was carried out in twelve cases (32%). 30 patients with advanced stage received brachytherapy boost after 50-66.5 Gy (mean, 60 Gy) locoregional external beam irradiation (EBI) and 7 patients with early stage (T1-2, N0) were managed locally with wide tumor excision and sole brachytherapy. 4 of them underwent neck dissection and the others were subjected to 50 Gy regional EBI. The mean dose of boost and sole brachytherapy was 18 Gy and 28 Gy, respectively., Results: . The median follow-up time for surviving patients was 51 months. The 7 sole brachytherapy patients are living with no evidence of disease. For patients treated with EBI and brachytherapy boost, the 5-year actuarial rate of local, locoregional recurrence-free and overall survival was 60%, 52% and 46%, respectively. For all patients in univariate analysis larger tumor size (T4 vs. T1-3) was significant negative predictor of local (RR: 7.23) and locoregional control (RR: 3.87), but nodal involvement was not. Delayed soft tissue ulceration and osteoradionecrosis occurred in 4 (13%) EBI and brachytherapy treated patients. None of the sole brachytherapy patients experienced severe late radiation toxicity., Conclusion: . EBI combined with interstitial HDR brachytherapy boost result in acceptable local tumor control with low incidence of late side effects in patients with advanced disease. Fractionated sole HDR brachytherapy following tumor excision is a feasible treatment option for patients with early stage cancer and gives excellent local results.

Serum thyroglobulin (Tg) is a suitable marker for differentiated thyroid carcinoma following total thyroid ablation. Between 1998 and 2003, serum samples from 715 papillary and 179 follicular tumor patients treated with total/nearly total thyroidectomy and radioiodine ablation therapy were collected. According to the "Guidelines for Oncotherapy in Hungary", serum Tg, antithyroglobulin antibody (TgAb), TSH and FT4 levels were measured in periods of 3 months following the first treatment and of 6 months after 2 years. In the present work the prognostic value of Tg and TgAb data of cancer patients with hormone substitution therapy were evaluated individually and retrospectively. Serum Tg and TgAb concentrations were measured with a highly sensitive immunoradiometric (IRMA) method, and with a second generation, broad epitope specificity competitive radioimmunoassay, respectively. TSH levels determined by fourth generation LIAISON kit were in a range of 0.05-0.10 mIU/L. Accuracy of measuring of Tg <1 ng/ml made it possible to select the low cut-off level (Tg <2 ng/ml) following total thyroidectomy. In the predominant part of TSH-suppressed patients (746/774, 96%) the serum Tg concentration was below the cut-off level of 2 ng/ml. The sensitivity of Tg determination in 59 TSH-suppressed thyroid cancer patients with lung and bone metastases was as high as 86 to 100%. On the contrary, the number of false negative data was high in cases with lymph node metastases of papillary cancer, and sensitivity did not exceed 62%. Specificity and sensitivity of Tg in TgAb negative patients were 91 to 100%. Based on our results it could be concluded that measuring of Tg and TgAb, using a current IRMA method and a second generation RIA kit, proved to be effective tools for the postoperative monitoring of differentiated thyroid tumours. It has to be noted that determination of TgAb is highly recommended for the adequate interpretation of serum Tg levels. Persistently high and/or increasing serum TgAb concentration with low Tg result had a diagnostic value during the follow-up and can be connected with the recurrence or persistence of the differentiated thyroid cancer.

Objectives/hypothesis: The main objective of this study was to investigate the effect of the administration of a novel immunoadjuvant, leukocyte interleukin injection, as part of an immuno-augmenting treatment regimen on the peritumoral and intratumoral subpopulations of the tumor infiltrating mononuclear cells and on the epithelial and stromal components, when administered to patients with advanced primary oral squamous cell carcinoma classified as T2-3N0-2M0, as compared with disease-matched control patients (not treated with leukocyte interleukin injection)., Study Design: Multicenter Phase I/II clinical trial. Fifty-four patients from four clinical centers were included in the dose-escalating study (27 in each group [leukocyte interleukin injection-treated and control groups]). Cumulative leukocyte inter-leukin injection doses were 2400, 4800, and 8000 IU (as interleukin-2 equivalent)., Methods: Paraffin-embedded tumor samples obtained at surgical resection of the residual tumor (between days 21 and 28 after treatment initiation) were used. Histological analysis, necrosis evaluation, and American Joint Committee on Cancer grading were performed from H&E-stained sections. Immunohistochemical analysis was performed on three different tumor regions (surface, zone 1; center, zone 2; and tumor-stroma interface, zone 3). Trichrome staining was used to evaluate connective tissue, and morphometric measurements were made using ImagePro analysis software. Cell cycling was determined by the use of Ki-67 marker., Results: Leukocyte interleukin injection treatment induced a shift from stromal infiltrating T cells toward intraepithelial T cells and posted a significant (P <.05) increase in intraepithelial CD3-positive T cells independent of the leukocyte interleukin injection dose, whereas the increase in CD25 (interleukin-2 receptor alpha [IL-2Ralpha])-positive lymphoid cells was significant only at the lowest leukocyte interleukin injection dose (P <.05). Furthermore, both low- and medium-dose leukocyte interleukin injection treatment induced a significant (P <.05) increase in the number of cycling tumor cells, as compared with control values., Conclusion: The results could be highly beneficial for patients with oral squamous cell carcinoma. First, leukocyte interleukin injection treatment induces T-cell migration into cancer nests and, second, noncycling cancer cells may enter cell cycling on administration of leukocyte interleukin injection. This latter effect may modulate the susceptibility of cancer cells to radiation therapy and chemotherapy. The findings may indicate a need to re-evaluate the way in which follow-up treatment (with radiation therapy and chemotherapy) of patients with head and neck cancer is currently approached.

In our prospective study we examined the use of low-dose paclitaxel concurrently with radiation for patients with locally advanced head and neck cancer, who were not eligible for concurrent chemoradiation due to their poor general condition. Twenty-six patients were treated with external beam radiotherapy and received concomitantly 2 mg/m(2) paclitaxel three times a week. Beside an acceptable efficacy (RR: 65%, 2-year overall survival 46%) the treatment was well tolerated and resulted in a favorable toxicity profile. This regimen is resource effective and allowed successive therapy if it was necessary and therefore may serve as an alternative for patients in poor condition with locally advanced head and neck cancer.

The bleomycin (BLM) sensitivity assay has been associated with the measuring of increased risk of individual susceptibility to cancer, when chromatid breaks per cell (b/c) induced by an in vitro treatment of lymphocytes with BLM are elevated. The high heritability of BLM sensitivity indicates a genetic background. We wished to clarify whether the test characterizes the head and neck cancer phenotype as compared not only with healthy individuals, but also with alcoholic patients (ALCs) whose exposure to tobacco and alcohol consumption were similar to that of head and neck cancer patients (HNCPs), but whose liver diseases were not cancerous. If the BLM test quantifies merely cancer susceptibility on an inherited basis, the mutagen sensitivity of HNCPs should differ from that of ALCs. Conventional chromosome analysis and the BLM assay were carried out on 156 HNCPs, 51 ALCs, 146 healthy non-smokers and non-drinkers and 149 non-drinking smokers. The spontaneous rates of chromosomal aberrations (CAs) in HNCPs, ALCs and healthy smokers were identical (2.8%), but differed significantly from the non-smoking controls (2.25%). Sporadic CAs were clearly associated with tobacco smoking, but not with health status. Mutagen sensitivity measured by the BLM test showed significantly (P < 0.04) elevated values not only in HNCPs (1.13 b/c), but also in ALCs (1.29 b/c) as compared with the controls (1.01 b/c). The main finding of the study was that a considerable proportion (46%) of Hungarian controls were mutagen sensitive, twice as many as in those populations reported by others so far. Our data suggest that the BLM test does not characterize susceptibility to cancer due to insignificant differences between HNCPs and ALCs (P = 0.12) under our conditions. However, the assay might be used as a biomarker to predict cancer susceptibility under circumstances when aberrant cell frequency is >or=2% and b/c is >or=1.

Mucosal melanomas comprise about 1% of all malignant melanomas and exhibit far more aggressive behaviour than that of skin melanomas: they are more inclined to metastatize into regional and distant sites or recur locally, regionally or in distant locations, resulting in a high rate of cause-specific death. Mucosal melanomas in the head and neck region account for half of all mucosal melanomas, occurring mainly in the upper respiratory tract, oral cavity and pharynx. They appear with equal gender distribution and with a peak incidence in the age range 60-80 years. In consequence of their hidden location, they are usually diagnosed in a locoregionally advanced clinical stage, with a rate of 5-48% of regional and 4-14% of distant dissemination. The typical therapeutic approach is surgery, postoperative irradiation and systemic therapy. Local control with either surgery or radiotherapy is frequently (60- 70%) achieved, but the rates of local, regional and distant recurrences are high (50-90%, 20-60% and 30-70%, respectively). The reported 5-year actual survival rates are poor (17-48%), which is attributed mainly to a haematogenous dissemination. These characteristics demonstrate that identification of the precursor lesions and more effective local and systemic approaches are needed to improve the therapeutic results.

Objective of the Study: to investigate the clinical outcome of HNSCC patients, and their hormonal status., Method: The liver function (GGT), hypophysis gonadotrop hormone (FSH, LH, prolactin) and sexsteroid hormone serum levels were examined in 130 male HNSCC patients. Clinical parameters for age, primary tumor site and clinical tumor stage were also recorded., Results: The survival was disadvantageously influenced by the following parameters: age, the presence of lymph node metastasis, advanced tumor stage, the lower than normal testosterone and the higher than normal FSH serum levels., Conclusion: Elevated FSH and decreased testosterone serum levels showed significant correlation with the survival of head and neck cancer patients. The better understanding of their exact role in the biology of HNSCC requires further investigations.

The authors' aim was to introduce a simple, safe and reliable method for reconstruction of soft tissue defects after excision of carcinomas of the tongue, tongue base and posterior part of the floor of the mouth. The musculocutaneous flaps are options of larger soft tissue defects in the maxillofacial area. After excision of a tongue-tongue base tumour with mandibular splitting method a platysma myocutaneous flap was applied for reconstruction. The flap was taken from an appropriate place convenient to functional acceptions and was adapted anatomically into the defect. The result was that the patient healed primarily with undisturbed blood circulation of the flap. The functional rehabilitation period was short, the flap tolerated the irradiation. The authors observed that the use of the platysma island flap can be an option for reconstruction of defects after ablative surgery on the tongue-tongue base. This simple method worked reliable even after intra-arterial cytostatic treatment. The acceptable functional result depends on the placement of the island flap on the neck flap prepared for neck dissection.

HPVs commonly cause proliferative lesions of squamous epithelium, and infection with certain HPV types carries a high risk of malignant transformation. We used molecular techniques to detect and type HPV in papillomas and carcinomas in the oral cavity and esophagus. DNA was extracted from 150 fresh or paraffin embedded biopsy specimens, and analyzed for HPV by PCR with 15 sets of consensus primers directed to conserved regions of L1 gene, three sets of HPV16E6 primers (specific for the HPV 16 prototype and L83V variant), and sets of primers specific for the E6 gene of other mucosa type HPVs including HPV 6, 11, 16, 18, 52, 58, 66 and 73. Overall, HPV sequences were detected in 61 of 150 specimens. HPV DNA sequences were detected in 16/32 specimens in the oropharyngeal region, in 13/36 specimens in larynx and 32/82 specimens in esophagus. Papillomas contained only the episomal form of HPV 16. In the esophagus, the most common type was HPV 73. In all specimens examined, HPV 6/11 (4/150), HPV 16 (23/150), HPV 35 (1/150), HPV 45 (1/150), HPV 54 (1/150), HPV 58 (1/150), HPV 61 (1/150), HPV 66 (1/150), HPV 68 (2/150), HPV 70 (3/150), HPV 72 (1/150), HPV 73 (16/150), double HPV infection (2/150), and unidentified HPV type (4/150) was detected. Interestingly, HPV was found in all verrucous carcinomas and in 18/22 basaloid squamous cell carcinomas. HPV16E6 T350G mutant were observed only in two of eight carcinomas. Using correspondence analysis, a segregation of specific virus types in specific clinico-pathologic lesions (verrucous carcinoma and basaloid squamous cell carcinoma) was proved. It was shown that the relative rates of the HPV positive tumors were significantly higher in women than in men. The synergic action of mucosal irritation and HPV infection may be necessary for the development of the papillomas and the specific types of carcinomas in the oral cavity and in the esophagus.

Unlabelled: Head and neck squamous cell carcinoma (HNSCC) is diagnosed mainly in male patients (more than 80% of the cases) with a history of smoking and heavy alcohol consumption. However, only a few percent of all alcoholics develop head and neck cancer., Objective of the Study: to investigate the hormonal status in HNSCC patients as compared to healthy controls and alcoholic persons in order to find changes, if any, characteristic for cancer., Method: The liver function expressed by gamma-GT levels, the hypophysis gonadotrop hormone (FSH, LH, prolactin) and sex steroid hormone serum levels were examined in 130 male HNSCC patients, in 54 men with alcoholic liver disease but without any known cancer and in 56 healthy men as controls., Results: When compared to the healthy controls, both alcoholics and tumor patients had abnormal liver function, testosterone, sex hormone binding globuline and prolactin levels, reflecting the presence of alcoholic liver disease in tumor patients as well. However, abnormally elevated circulating FSH (p<0.005) and LH (p<0.0003) levels were present only in the tumor patients., Conclusion: Sex steroid hormone abnormalities are common among head and neck cancer patients, mainly as results of the chronic alcoholic liver disease. Elevation of FSH and LH levels suggests a potential role of these hormones in the formation of head and neck cancer. The exact role of the hypothalamus-hypophysis-liver axis in the biology of head and neck cancer requires further investigations.

Because of unfavourable cancer mortality statistics of Hungary, the search of different biomarkers is one of the most important demands of the national primary cancer prevention programme. The aim of this study was to clarify the usefulness of bleomycin sensitivity assay elaborated in the USA, and to find whether it serves under our environmental conditions as a biomarker of individual sensitivity and risk for head and neck cancer, beside chromosomal aberration analysis. The test reflecting mutagen sensitivity is based on the mean values of chromatid breaks induced by bleomycin in vitro in a single lymphocyte (break/cell = b/c). Since cancer formation is influenced by environmental mutagens, in contrast to others, their 111 head and neck cancer patients were matched not only with 230 healthy controls (106 nonsmokers and 124 smokers), but also with 44 strong alcoholic and smoking patients with liver diseases whose lifestyle did not differ from that of the cancer patients. According to the results of conventional chromosome analysis, the aberrant cell frequency was the highest in the cancer patients (3.34%), while in the alcoholics (2.73%) and healthy smokers (2.88%) the values were similar. Thus, the genetic instability occurring in the form of elevated rate of spontaneous chromosomal aberrations was mostly expressed in head and neck cancer patients. Mutagen sensitivity measured by the b/c values of bleomycin assay was significantly higher in both the cancer (1.16 b/c) and the alcoholic patients (1.34 b/c) compared with the controls (1.0 b/c). The bleomycin sensitivity assay, therefore, seems to be the biomarker not only of cancer, but also the disease of the same etiology such as alcohol-related liver disease. However the method is not suitable for the assessment of individual cancer risk because of the high variability of b/c values in each group, and their considerable overlapping with the controls. It can also be supported with extremely high mutagen sensitivity of Hungarian controls (63 and 67%), which is three-fold of US values (23%). The bleomycin sensitivity assay is not a selective biomarker if comparing to the controls, probably due to the action of more complex exposures under Hungarian environmental conditions. When estimating cancer risk, the results of conventional chromosome analysis offer more information than bleomycin sensitivity assay.