Education, tobacco smoking, alcohol consumption, and IL-2 and IL-6 gene polymorphisms in the survival of head and neck cancer

The association of education, tobacco smoking, alcohol consumption, and interleukin-2 (IL-2 +114 and -384) and -6 (IL-6 -174) DNA polymorphisms with head and neck squamous cell carcinoma (HNSCC) was investigated in a cohort study of 445 subjects. IL-2 and IL-6 genotypes were determined by real-time PCR. Cox regression was used to estimate hazard ratios (HR) and 95 percent confidence intervals (95 percentCI) of disease-specific survival according to anatomical sites of the head and neck. Mean age was 56 years and most patients were males (87.6 percent). Subjects with 5 or more years of schooling had better survival in larynx cancer. Smoking had no effect on HNSCC survival, but alcohol consumption had a statistically significant effect on larynx cancer. IL-2 gene +114 G/T (HR = 0.52; 95 percentCI = 0.15-1.81) and T/T (HR = 0.22; 95 percentCI = 0.02-3.19) genotypes were associated with better survival in hypopharynx cancer. IL-2 +114 G/T was a predictor of poor survival in oral cavity/oropharynx cancer and larynx cancer (HR = 1.32; 95 percentCI = 0.61-2.85). IL-2 -384 G/T was associated with better survival in oral cavity/oropharynx cancer (HR = 0.80; 95 percentCI = 0.45-1.42) and hypopharynx cancer (HR = 0.68; 95 percentCI = 0.21-2.20), but an inverse relationship was observed for larynx cancer. IL-6 -174 G/C was associated with better survival in hypopharynx cancer (HR = 0.68; 95 percentCI = 0.26-1.78) and larynx cancer (HR = 0.93; 95 percentCI = 0.42-2.07), and C/C reduced mortality in larynx cancer. In general, our results are similar to previous reports on the value of education, smoking, alcohol consumption, and IL-2 and IL-6 genetic polymorphisms for the prognosis of HNSCC, but the risks due to these variables are small and estimates imprecise.

Education, tobacco smoking, alcohol consumption, and IL-2 and IL-6 gene polymorphisms in the survival of head and neck cancer.

The association of education, tobacco smoking, alcohol consumption, and interleukin-2 (IL-2 +114 and -384) and -6 (IL-6 -174) DNA polymorphisms with head and neck squamous cell carcinoma (HNSCC) was investigated in a cohort study of 445 subjects. IL-2 and IL-6 genotypes were determined by real-time PCR. Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (95%CI) of disease-specific survival according to anatomical sites of the head and neck. Mean age was 56 years and most patients were males (87.6%). Subjects with 5 or more years of schooling had better survival in larynx cancer. Smoking had no effect on HNSCC survival, but alcohol consumption had a statistically significant effect on larynx cancer. IL-2 gene +114 G/T (HR = 0.52; 95%CI = 0.15-1.81) and T/T (HR = 0.22; 95%CI = 0.02-3.19) genotypes were associated with better survival in hypopharynx cancer. IL-2 +114 G/T was a predictor of poor survival in oral cavity/oropharynx cancer and larynx cancer (HR = 1.32; 95%CI = 0.61-2.85). IL-2 -384 G/T was associated with better survival in oral cavity/oropharynx cancer (HR = 0.80; 95%CI = 0.45-1.42) and hypopharynx cancer (HR = 0.68; 95%CI = 0.21-2.20), but an inverse relationship was observed for larynx cancer. IL-6 -174 G/C was associated with better survival in hypopharynx cancer (HR = 0.68; 95%CI = 0.26-1.78) and larynx cancer (HR = 0.93; 95%CI = 0.42-2.07), and C/C reduced mortality in larynx cancer. In general, our results are similar to previous reports on the value of education, smoking, alcohol consumption, and IL-2 and IL-6 genetic polymorphisms for the prognosis of HNSCC, but the risks due to these variables are small and estimates imprecise.

Genomics and proteomics approaches to the study of cancer-stroma interactions.

BACKGROUND: The development and progression of cancer depend on its genetic characteristics as well as on the interactions with its microenvironment. Understanding these interactions may contribute to diagnostic and prognostic evaluations and to the development of new cancer therapies. Aiming to investigate potential mechanisms by which the tumor microenvironment might contribute to a cancer phenotype, we evaluated soluble paracrine factors produced by stromal and neoplastic cells which may influence proliferation and gene and protein expression. METHODS: The study was carried out on the epithelial cancer cell line (Hep-2) and fibroblasts isolated from a primary oral cancer. We combined a conditioned-medium technique with subtraction hybridization approach, quantitative PCR and proteomics, in order to evaluate gene and protein expression influenced by soluble paracrine factors produced by stromal and neoplastic cells. RESULTS: We observed that conditioned medium from fibroblast cultures (FCM) inhibited proliferation and induced apoptosis in Hep-2 cells. In neoplastic cells, 41 genes and 5 proteins exhibited changes in expression levels in response to FCM and, in fibroblasts, 17 genes and 2 proteins showed down-regulation in response to conditioned medium from Hep-2 cells (HCM). Nine genes were selected and the expression results of 6 down-regulated genes (ARID4A, CALR, GNB2L1, RNF10, SQSTM1, USP9X) were validated by real time PCR. CONCLUSIONS: A significant and common denominator in the results was the potential induction of signaling changes associated with immune or inflammatory response in the absence of a specific protein.

Annexin A1 subcellular expression in laryngeal squamous cell carcinoma.

AIMS: Annexin A1 (ANXA1) is a soluble cytoplasmic protein, moving to membranes when calcium levels are elevated. ANXA1 has also been shown to move to the nucleus or outside the cells, depending on tyrosine-kinase signalling, thus interfering in cytoskeletal organization and cell differentiation, mostly in inflammatory and neoplastic processes. The aim was to investigate subcellular patterns of immunohistochemical expression of ANXA1 in neoplastic and non-neoplastic samples from patients with laryngeal squamous cell carcinomas (LSCC), to elucidate the role of ANXA1 in laryngeal carcinogenesis. METHODS AND RESULTS: Serial analysis of gene expression experiments detected reduced expression of ANXA1 gene in LSCC compared with the corresponding non-neoplastic margins. Quantitative polymerase chain reaction confirmed ANXA1 low expression in 15 LSCC and eight matched normal samples. Thus, we investigated subcellular patterns of immunohistochemical expression of ANXA1 in 241 paraffin-embedded samples from 95 patients with LSCC. The results showed ANXA1 down-regulation in dysplastic, tumourous and metastatic lesions and provided evidence for the progressive migration of ANXA1 from the nucleus towards the membrane during laryngeal tumorigenesis. CONCLUSIONS: ANXA1 dysregulation was observed early in laryngeal carcinogenesis, in intra-epithelial neoplasms; it was not found related to prognostic parameters, such as nodal metastases.

Universal image compression using multiscale recurrent patterns with adaptive probability model.

In this work, we further develop the multidimensional multiscale parser (MMP) algorithm, a recently proposed universal lossy compression method which has been successfully applied to images as well as other types of data, as video and ECG signals. The MMP is based on approximate multiscale pattern matching, encoding blocks of an input signal using expanded and contracted versions of patterns stored in a dictionary. The dictionary is updated using expanded and contracted versions of concatenations of previously encoded blocks. This implies that MMP builds its own dictionary while the input data is being encoded, using segments of the input itself, which lends it a universal flavor. It presents a flexible structure, which allows for easily adding data-specific extensions to the base algorithm. Often, the signals to be encoded belong to a narrow class, as the one of smooth images. In these cases, one expects that some improvement can be achieved by introducing some knowledge about the source to be encoded. In this paper, we use the assumption about the smoothness of the source in order to create good context models for the probability of blocks in the dictionary. Such probability models are estimated by considering smoothness constraints around causal block boundaries. In addition, we refine the obtained probability models by also exploiting the existing knowledge about the original scale of the included blocks during the dictionary updating process. Simulation results have shown that these developments allow significant improvements over the original MMP for smooth images, while keeping its state-of-the-art performance for more complex, less smooth ones, thus improving MMP's universal character.

[Clinical and epidemiological characteristics of squamous cell carcinoma of the oral cavity in women]. / Características clínico-epidemológicas do carcinoma epidermóide de cavidade oral no sexo feminino.

BACKGROUND: Squamous cell carcinoma (SCC) of the oral cavity occurs mainly in the male population. The objective of the study is to identify the main clinical and epidemiological differences of the oral SCC between men and women. METHODS: Retrospective analysis of the charts of 228 cases of SCC of the oral cavity in women treated at the Head & Neck Surgery Service, Heliopolis Hospital, São Paulo, Brazil from 1977 to 1996. The clinical and epidemiological characteristics of these cases were compared with those of 849 male patients. RESULTS: The mean age of women was 60.7 years (ranging 2 to 100 years) and in the male group was 55.6 years (p<0.00001). In cases where the alcohol intake and tobacco use were absent, the tumors ocurred in older patients. The isolated tobacco use didn't affect the distribuction by age but for the alcohol intake (alone or combined with tobacco) the patients were younger. On the alcohol intake, 71% of the women and 8% of the man used no alcohol. The most common sites of tumors were tongue and floor of the mouth but in the women group the incidence of tumors in these sites were 43% compared with 61% in the men. CONCLUSIONS: The highest incidence of SCC the of oral cavity occurs later in women, than in men. This could be explained by a lesser exposure to alcohol and tobacco in women. Other factors seem to be involved in this issue.

Transcutaneous fine needle aspiration biopsy of the preepiglottic space.

OBJECTIVE: To evaluate transcutaneous fine needle aspiration biopsy of the preepiglottic space for staging supraglottic squamous cell carcinoma. STUDY DESIGN: We studied 28 patients who underwent total or horizontal supraglottic laryngectomy as their main therapy modality due to supraglottic squamous cell carcinoma, followed in some cases by adjuvant radiation therapy. All the patients underwent transcutaneous fine needle aspiration. RESULTS: The cytopathologic examination of the material obtained by aspiration was compared to the histopathologic analysis of the laryngectomy specimens; the efficiency was 96.4%. The method did not cause any morbidity. CONCLUSION: Transcutaneous fine needle aspiration biopsy of the preepiglottic space is useful for preepiglottic space evaluation, with a high correlation with histopathologic results and no morbidity.

Head and neck squamous cell carcinoma in childhood.

BACKGROUND: Squamous cell carcinoma (SCC) of the head and neck region is rare in young patients and even less frequent in children 15 years or younger children. The patients reported in the literature are isolated cases and their management is always difficult because there is no large experience or a convincing theory to support treatment decisions for every child. PROCEDURES AND RESULTS: Four patients aged 15 years or younger were treated for SCC of head and neck between 1977 and 1995 at the Head and Neck Service of Heliópolis Hospital, São Paulo, Brazil, and with this paper we are reporting our experience with their treatment, including a genetic investigation in two cases (immunohistochemical analysis using monoclonal antibodies against p53 and c-erbB-2 oncogenes). These patients had no history of tobacco or ethanol abuse and no history of cancer in their families. Many authors attribute an unusual aggressiveness to SCC in childhood, with propensity to locoregional recurrence and high death rates and therefore, propose aggressive multidisciplinary therapy. Our cases, with the exception of one, had an early diagnosis and were treated using the same method we use for adults; the results were very good. CONCLUSIONS: We recommend for these cases the same protocol as for older patients. In these cases, however, the primary lesion is resected with a safety margin which is usually 2 to 3 mm larger than usual safety margins and selective neck dissection is routinely indicated. This management is adopted in an attempt to avoid postoperative irradiation which may prove to be dangerous in the future for young patients. On the other hand, we recognize that due to a small number de patients, definitive treatment recommendations cannot be made at this time.

Chagas' disease: an algorithm for donor screening and positive donor counseling.

Classical serological screening assays for Chagas' disease are time consuming and subjective. The objective of the present work is to evaluate the enzyme immuno-assay (ELISA) methodology and to propose an algorithm for blood banks to be applied to Chagas' disease. Seven thousand, nine hundred and ninety nine blood donor samples were screened by both reverse passive hemagglutination (RPHA) and indirect immunofluorescence assay (IFA). Samples reactive on RPHA and/or IFA were submitted to supplementary RPHA, IFA and complement fixation (CFA) tests. This strategy allowed us to create a panel of 60 samples to evaluate the ELISA methodology from 3 different manufacturers. The sensitivity of the screening by IFA and the 3 different ELISA's was 100%. The specificity was better on ELISA methodology. For Chagas disease, ELISA seems to be the best test for blood donor screening, because it showed high sensitivity and specificity, it is not subjective and can be automated. Therefore, it was possible to propose an algorithm to screen samples and confirm donor results at the blood bank.

The value of therapeutic planning and the degree of experience of the surgical team on the results of cancer treatment of the larynx and hypopharynx.

This is a prospective study supported by 170 cases of epidermoid carcinoma of the larynx or hypopharynx, treated during the period from January of 1981 to January of 1988, at the Head and Neck Surgery Service of the Heliópolis Hospital Complex, São Paulo. The objective of this project was to evaluate the importance of surgeon experience with regard to the rates of post-operative complications and the rates of relapse and survival. The results of the 8 surgical specialists who integrate the permanent staff at the institute and who different varying degrees of experience with regard to time spent exercising their specialties were compared. The results obtained did not show a significant difference among the various surgeons, and this uniformity is explained by the fact that all the therapeutic planning was elaborated through consensus of the whole group, and this could have minimized the effect of experience of a surgeon responsible for the operation. The authors emphasize the importance of pre-operative evaluation for good results and propose that it is in the direction of complete mastery of preliminary work in the area that programs for the formation of new specialists should be directed.

Self-instruction in anatomy for medical students.

The authors describe the results of the use of a self-instructional material (study guide-book) during two Anatomy courses (cardio-respiratory and locomotor) given to first year medical students of São Paulo University. The rate of approval was considered very good in both courses.

Odontogenic adenomatoid tumor of the mandible (adenoameloblastoma).

Adenoameloblastoma may recur when treated incompletely by curettage. In the rare case of recurrence, an extensive and mutilating resection may become necessary. A correct diagnosis must be made in cases of atypical ameloblastomas in order to avoid unnecessary radical surgery. In doubtful cases, biopsy with histopathologic examination is indicated. Acknowledgment: We thank Mrs. Frieda Werebe for organizing this manuscript.

Ewing's sarcoma of the mandible.

Ewing's sarcoma of the head and neck, particularly of the mandible, has a low incidence of occurrence (fifty-five cases in the literature). The present case report demonstrates well the clinical, diagnostic, and therapeutic features in a patient treated at the Head and Neck Service of the Fundação Antonio Prudente, São Paulo, Brazil. The etiologic, clinical, histopathologic, and radiologic features are discussed, with the conclusion that radiation is the best therapeutic procedure when associated with chemotherapy.