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Biomedical subjects

L Barzan

Publications and source records attributed to L Barzan.

At least 19 recordsLinked to original sources

Body size and laryngeal cancer risk.

BACKGROUND: A few studies have analyzed the role of lifetime anthropometric measures on laryngeal cancer risk. PATIENT AND METHODS: This relation was investigated using a multicentre case-control study from Italy, conducted between 1992 and 2000, and including 460 incident, histologically confirmed laryngeal cancer cases, and 1088 controls admitted to the same network of hospitals as cases for acute, non neoplastic condition. Odds ratios (OR) and corresponding 95% confidence intervals (CI) were obtained from multiple logistic regression, including terms for major confounding factors, such as physical activity and energy intake. RESULTS: An inverse association with laryngeal cancer risk was found for body mass index (BMI) in both sexes (OR for the lowest compared to the highest quintile was 1.47, 95% CI 0.93-2.33 in men and 8.11, 95% CI 1.38-47.66 in women) and for BMI at age 50 years (OR=1.65, 95% CI 0.88-3.11) in men and 7.84, 95% CI 0.69-88.58 in women). An inverse association was also observed with waist-to-hip ratio (WHR) at diagnosis in men only (OR=4.56, 95% CI 2.62-7.95 for the lowest compared to the highest quintile). CONCLUSIONS: This study supports the existence of a relation between leanness and laryngeal cancer risk. In particular, men with less abdominal fat (characterized by a lower WHR) had an increased risk of laryngeal cancer.

Adult↗

An extended use of the sentinel node in head and neck squamous cell carcinoma: results of a prospective study of 100 patients.

Most studies concerning the use of the sentinel node technique in head and neck cancers have included clinically N0 patients with primary early stage tumours of the oral cavity or upper part of oropharynx; furthermore, node sampling has been performed during the same session, but separately from the tumour. The perspective of avoiding unnecessary neck dissection, without increasing the risk of delayed diagnosis of lymph node metastasis, is rewarding, not only for early stage tumours of the oral cavity but also for tumours in advanced stages and/or at different anatomic sites. In the attempt to establish the reliability of extended use of the sentinel node technique, 100 consecutive untreated patients (from 1999 to 2002) with tumours located in the oral cavity, oropharynx, hypopharynx and larynx, at any T stage, entered the study. N+ patients with paramedian tumours and contralateral clinically negative nodes were also enrolled. After injection of the 99mTc albumin microcolloid, pre- and intra-operative evaluations with a gamma-probe were done. N0 patients (59) were submitted to mono- or bilateral selective neck dissection; the N+ patients (41) received homolateral dissection of all levels and contralateral selective dissection. An en bloc resection of the tumour was performed both in N0 and N+ patients. In the N0 group, histological examination showed no evidence of metastases in "hot" nodes in 34 patients and also the remaining nodes were negative. Metastases were found in one or more of the gamma-probe positive nodes (14 cases), or in a closely located node at the same level (2 cases) or in a node close to a "hot" area of the submandibular salivary gland (1 case). In 8 patients, lymphoscintigraphy did not identify any sentinel node and histology of all lymph nodes was negative for metastases. In the N+ group, no metastases were found in the sentinel nodes of 21 patients and also the remaining nodes were negative; in 4 patients, metastases were found in sentinel nodes. In 16 patients, lymphoscintigraphy did not identify any sentinel node and histology of all lymph nodes was negative for metastases. In no patients were metastases found outside the level containing the lymph node identified as sentinel by the gamma-probe. In conclusion, the strategy of the sentinel node is reliable, but, to be confirmed as a standard approach, it requires trials with a larger number of patients. The technique requires a multidisciplinary and well "amalgamated" team. It may likely be used also in T3 and T4 oro-hypopharyngeal and laryngeal primary tumours and to determine surgical treatment of the contralateral neck in patients with N2a, N2b, N3 on T close to the midline.

Adult↗

Nasopharyngeal cancer WHO type II-III: monoinstitutional retrospective analysis with standard and accelerated hyperfractionated radiation therapy.

The aim of this study is to assess the impact of prognostic factors in patients with locoregionally advanced nasopharyngeal cancer (NPC), WHO type II-III, treated with two different radiation therapy (RT) schedules: standard radiation therapy (SRT), and accelerated hyperfractionated radiation therapy (HART), with or without sequential chemotherapy. Between January 1986 and December 1999, 78 consecutive NPC patients were treated either with SRT (until August 1993) or with HART (from September 1993). Of the 78 patients, 60 were males and 18 females, the median age was 56 years (range 14-83). Nine patients had a non-keratinizing carcinoma (WHO type II) and 69 an undifferentiated carcinoma (WHO type III). Five-year overall survival rate (OS) was 62%. Two months after RT, 73 patients were in complete remission. Disease-free survival (DFS) rates at 5 years were: 85% for the HART and 59% for the SRT group, respectively. A multivariate analysis, age (hazard ratio, HR=4.17 for > or = 60 vs. <50 years) and N-stage (HR=3.56 for N3a-N3b vs. N0-N1) were significant for survival, whereas N-stage (HR=8.23 for N3a-N3b vs. N0-N1) and RT schedule (HR=0.30 for HART vs. SRT) were significant for DFS. In our experience, HART achieved higher DFS rates than SRT; however, HART did not favourably affect OS. Toxicity was comparable in the two RT schedules.

Adolescent↗

Combined effect of tobacco and alcohol on laryngeal cancer risk: a case-control study.

OBJECTIVE: To provide information on the effects of alcohol and tobacco on laryngeal cancer and its subsites. METHODS: This was a case-control study conducted between 1992 and 2000 in northern Italy and Switzerland. A total of 527 cases of incident squamous-cell carcinoma of the larynx and 1297 hospital controls frequency-matched with cases on age, sex, and area of residence were included. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using multiple logistic regression. RESULTS: In comparison with never smokers, ORs were 19.8 for current smokers and 7.0 for ex-smokers. The risk increased in relation to the number of cigarettes (OR = 42.9 for > or = 25 cigarettes/day) and for duration of smoking (OR = 37.2 for > or = 40 years). For alcohol, the risk increased in relation to number of drinks (OR = 5.9 for > or = 56 drinks per week). Combined alcohol and tobacco consumption showed a multiplicative (OR = 177) rather than an additive risk. For current smokers and current drinkers the risk was higher for supraglottis (ORs 54.9 and 2.6, respectively) than for glottis (ORs 7.4 and 1.8) and others subsites (ORs 10.9 and 1.9). CONCLUSIONS: Our study shows that both cigarette smoking and alcohol drinking are independent risk factors for laryngeal cancer. Heavy consumption of alcohol and cigarettes determined a multiplicative risk increase, possibly suggesting biological synergy.

Adult↗

Squamous cell carcinoma of the hypopharynx treated with surgery and radiotherapy.

A series of squamous cell carcinomas (SCC) of the hypopharynx treated with combined surgery and radiotherapy is presented to highlight the results of treatment at an early stage of disease. A retrospective mono-institutional analysis was performed on 153 previously untreated patients with SCC of the hypopharynx, seen between 1980 and 1995 at our institution. Univariate and multivariate analyses were performed using the Cox proportional hazard model. The overall five-year specific, and non-specific, disease survival rates were 68 per cent (95 per cent confidence interval, CI: 60-77) and 47 per cent (95 per cent CI: 39-56), respectively. Compared with other series, this study is characterized by treatment at an earlier stage, better prognosis, and a higher number of multiple malignancies. Twenty-two per cent of hypopharyngeal SCCs were diagnosed during the staging procedures for a different head and neck SCC and 14 per cent during the follow-up for a previous tumour. Multivariate survival analysis of clinical and pathological factors confirmed the clinical class of tumour (T) and node (N) and the nodal capsular rupture as prognosticators of disease.

Adult↗

The EORTC quality of life questionnaire-head and neck 35 in Italian laryngectomized patients. European organization for research and treatment of cancer.

The aim of this study was to test the validity and reliability of the European organization for research and treatment of cancer (EORTC) quality of life questionnaire (QLQ)-head and neck (H&N) 35 in Italian laryngeal cancer patients. The original questionnaire was developed by the EORTC quality of life (QoL) study group and tested in H&N cancer patients from Norway, Sweden, and the Netherlands. The Italian translation of the questionnaire used in this study was made by a team of the CRO, National Cancer Institute, using a double-back translation method between independent translators. The translated EORTC QLQ-H&N35 was given to 99 patients with H&N cancer who had undergone total laryngectomy 1-26 years before and had been then treated with radiotherapy and, in some cases, chemotherapy. The questionnaire was re-administrated to 33 patients after 1 month to test its stability over time. It was structurally made up of seven scales (pain, swallowing, sense, speech, social eating, social contact, and sexuality) and 11 single items that considered the most important clinical aspects characterizing the QoL in H&N cancer patients. The statistical analysis of the indexes of validity and reliability confirmed the results obtained with other linguistic versions of the questionnaire. Our Italian version of the EORTC QLQ-H&N35 proved to be a statistically valid instrument to assess QoL in laryngectomized patients.

Aged↗

Comparison of the effect of smoking and alcohol drinking between oral and pharyngeal cancer.

To compare the separate and combined effects of alcohol drinking and smoking between the 2 sites, we evaluated 274 men with oral cancer, 364 with pharyngeal cancer and 1,254 controls, frequency-matched for age and area of residence, from Italy and Switzerland. Extremely elevated risk increases for oral cancer (odds ratio, OR = 228) and pharyngeal cancer (OR = 100) were found for the highest joint level of drinking (>/=77 drinks/week) and smoking (>/=25 cigarettes/day). Ratios of ORs between oral cancer and pharyngeal cancer vs. controls, obtained by polytomous logistic regression, suggested that the risk increase for oral cancer was about 2-fold greater than that for pharyngeal cancer at each combined level of smoking and drinking, except at low levels of drinking in smokers. A clear departure from risk difference additivity was present for both oral and pharyngeal cancer in individuals heavily exposed to both factors versus non-smoking abstainers/light drinkers. Our findings thus help explain observations from descriptive epidemiology that, if smoking level in a population does not change substantially, but alcohol consumption increases, increase in oral cancer would be greater than at any other site in the upper aero-digestive tract, including cancer of the pharynx.

Adult↗

Loss of heterozygosity at 10q in tumors of the upper respiratory tract is associated with poor prognosis.

Frequent loss of a specific chromosomic region in cancers is often associated with inactivation of a tumor-suppressor gene. The long arm of chromosome 10 is deleted in several types of tumor, among them squamous-cell carcinomas of the head and neck (HNSCC). To determine the role of 10q deletions in the tumorigenesis of the upper respiratory tract, 47 HNSCCs were examined for loss of heterozygosity (LOH) at 10q: 43% of the cases analyzed showed LOH at 10q, and 2 distinct hot spots of deletion were identified, at 10q22-23 and 10q25-26. The possible involvement of pTEN/MMAC1, a tumor-suppressor gene mapped at 10q23, was also evaluated. No mutation, homozygous deletion or loss of expression of pTEN/MMAC1 was detected, indicating that inactivation of this gene plays a minor role in HNSCC development. Interestingly, the frequency of deletion at 10q was greater in invasive carcinoma than in adjacent carcinoma in situ, and a significant association between LOH and poor prognosis was observed. Taken together, our results suggest the presence in the long arm of chromosome 10 of (a) tumor-suppressor gene(s) other than pTEN/MMAC1 and presumably involved in the malignant progression of tumors of the upper respiratory tract. Int. J. Cancer (Pred. Oncol.) 84:432-436, 1999.

Blotting, Southern↗

Food groups, oils and butter, and cancer of the oral cavity and pharynx.

To elucidate the role of dietary habits, a study was carried out in 1992-1997 in the province of Pordenone in Northeastern Italy, and those of Rome and Latina in central Italy. Cases were 512 men and 86 women with cancer of the oral cavity and pharynx (lip, salivary glands and nasopharynx excluded) and controls were 1008 men and 483 women who had been admitted to local hospitals for a broad range of acute non-neoplastic conditions. The validated dietary section of the questionnaire included 78 foods or recipes and ten questions on fat intake patterns. After allowance for education, smoking, alcohol and total energy intake, significant trends of increasing risk with increasing intake emerged for soups, eggs, processed meats, cakes and desserts, and butter. Risk was approximately halved in the highest compared to the lowest intake quintile for coffee and tea, white bread, poultry, fish, raw and cooked vegetables, citrus fruit, and olive oil. The inverse association with oils, especially olive oil, was only slightly attenuated by allowance for vegetable intake. Thus, frequent consumption of vegetables, citrus fruit, fish and vegetable oils were the major features of a low-risk diet for cancer of the oral cavity and pharynx.

Adult↗

Immunological changes in peripheral blood and in lymphoid tissue after treatment of HIV-infected subjects with highly active anti-retroviral therapy (HAART) or HAART + IL-2.

This study presents the immunophenotypic and functional analysis of lymphocyte subsets obtained from peripheral blood and lymphoid tissue from HIV+ individuals treated with highly active anti-retroviral therapy (HAART) alone or in combination with 6 million units international (MUI) s.c. IL-2. Before treatment, the HIV+ patients had reduced CD4 and increased CD8 values in the peripheral blood and lymphoid tissue and impaired cytokine production by peripheral blood mononuclear cells (PBMC). After 24 weeks of treatment, all the HIV+ patients demonstrated increased CD4 values in peripheral blood and lymphoid tissue. The use of IL-2 did not promote an additional CD4 expansion compared with HAART alone; increased 'naive' and CD26+ CD4 cells and reduced CD8 cells were found in the peripheral blood and lymphoid tissue of the IL-2-treated, but not of the HAART-treated patients. Both types of treatment induced a significant reduction of the CD8/CD38+ cells. While HAART alone had negligible effects on cytokine production by PBMC, the combined use of HAART + IL-2 was unable to increase the endogenous production of IL-2, but caused an increase of IL-4, IL-13 and interferon-gamma (IFN-gamma) and a reduction of monocyte chemoattractant protein-1 (MCP-1) production. These data suggest that, although in this schedule IL-2 has minimal efficacy on CD4 recovery when compared with HAART alone, it produces an increase of 'naive' and CD26+ CD4 cells and a partial restoration of cytokine production. These data may be used to better define clinical trials aiming to improve the IL-2-dependent immunological reconstitution of HIV-infected subjects.

Adult↗

Radiation treatment of glottic squamous cell carcinoma, stage I and II: analysis of factors affecting prognosis.

PURPOSE: At least in some European Countries, there is still considerable controversy regarding the choice between surgery and radiotherapy for the treatment of patients with early laryngeal-glottic carcinoma. METHODS AND MATERIALS: Two hundred and forty-six patients with laryngeal-glottic neoplasms, Stage I-II, were treated with radical radiotherapy. Before radiotherapy the patients were evaluated to determine the surgical procedure of choice. Either 66-68.4 Gy (33-38 fractions) or 63-65 Gy (28-29 fractions) of radiation therapy (RT) were administered. The overall disease free survival was determined for each subgroup of patients. Univariate and multivariate analyses were performed to determine significant prognostic variables. RESULTS: Five- and 10-year overall survival rates were 83 and 72%, respectively. At a median follow-up of 6 years 204 patients are alive and disease free. No patient developed distant metastases. One patient died of a large local recurrence, 38 patients died of causes unrelated to their tumor, and 3 patients were lost to follow-up. The multivariate analysis confirmed that performance status (PS), macroscopic presentation of the lesion, and persistence of dysphonia after radiotherapy are significant prognostic factors. CONCLUSIONS: According to the multivariate analysis, the patients with PS > 80 and with exophytic lesions are eligible for radical RT. The surgical procedure proposed for each patient was not found to be an independent prognostic factor.

Adult↗

Combined radiotherapy and bleomycin in patients with inoperable head and neck cancer with unfavourable prognostic factors and severe symptoms.

The aim of this study was to assess the feasibility of concurrent split course radiotherapy and low-dose bleomycin in the treatment of unresectable head and neck cancer with unfavourable prognostic factors and severe symptoms. The clinical outcome of the treatment was assessed in terms of local disease control, symptom relief and toxicity. Between 1990 and 1996, 58 patients with squamous cell carcinoma of the head and neck, stage III or IV, were treated by radiotherapy (50 Gy/20 fractions) and simultaneous bleomycin (60 mg/6 fractions). Local control of disease, overall response, symptom relief and acute toxicity were evaluated. The rate of disease local control was 69% with a median response duration of 7 months (range 2-43+). The symptom relief rate was 81%. Mucositis was the prominent toxicity: G3 mucositis was reported in 27 patients. In conclusion, the treatment was feasible. A good palliation of symptoms and a good rate of local response were obtained. Moreover, toxicity was tolerable and the rate of hospitalisation was low.

Aged↗

Microsatellite instability in squamous cell carcinomas of the head and neck related to field cancerization phenomena.

Patients affected by squamous cell carcinoma of the head and neck (HNSCC) show frequent occurrence of multiple cancers and widespread precancerous lesions in the mucosa of the upper respiratory tract, a phenomenon known as field cancerization. In this study, we investigated the role of genetic instability in the development of HNSCC and in particular in tumour multiplicity phenomena of the upper respiratory tract. For this purpose, we analysed microsatellite instability (MI) and loss of heterozygosity (LOH) at 20 loci mapping on five chromosomal arms in 67 HNSCC patients, 45 of whom had a single cancer and 22 had multiple primary tumours. The possible involvement of the hMLH1 gene in genetic instability and as a potential target of 3p21 deletion phenomena in head and neck cancers was also investigated. Our data indicate that mismatch repair-related genetic instability plays a minor role in the carcinogenesis of HNSCC and in tumour multiplicity of the head and neck region. Moreover, our results exclude a role for the hMLH1 gene as a determinant of MI and as a specific gene target of deletion at 3p21 in HNSCC. We conclude that presumably other genetic mechanisms, such as those hypothesized for MI-negative hereditary non-polyposis colorectal cancer patients, may play a major role in the carcinogenesis of the mucosa of the upper respiratory tract.

Alleles↗

Overexpression of CDC25A and CDC25B in head and neck cancers.

The deregulation of several cell cycle-related genes participates in neoplastic transformation. Cell cycle progression is driven by cyclin-dependent kinases, which are positively regulated by association with cyclins and negatively regulated by binding to inhibitory subunits. The activity of cyclin-dependent kinases is also regulated by the phosphorylation status, which is controlled by the antagonistic action of wee1 kinase and CDC25 phosphatases. Three CDC25 genes are present in human cells: CDC25A, CDC25B, and CDC25C. These three genes function at different phases of the cell cycle. Whereas CDC25A and CDC25B are expressed throughout the cell cycle, with peak expression in G1 for CDC25A and in both G1-S-phase and G2 for CDC25B, CDC25C is predominantly expressed in G2. Several lines of evidence suggest a role for CDC25s as oncogenes. CDC25A and CDC25B cooperate with Ha-ras or loss of Rb1 in the oncogenic transformation of rodent fibroblasts. Moreover, they are transcriptional targets of c-myc, and CDC25A in particular plays an important role as a mediator of myc functions. On the basis of the evidence that CDC25 phosphatases can act as oncogenes, we analyzed the expression of CDC25A, CDC25B, and CDC25C genes in 20 squamous cell carcinomas of the head and neck by quantitative reverse transcription-PCR. Our results show that whereas CDC25C is expressed at a low level with no relevant differences between neoplastic tissue and normal mucosa, CDC25A and CDC25B are overexpressed in a large fraction of tumors.

Carcinoma, Squamous Cell↗

Screening for cancer of the head and neck: if not now, when?

There is as yet no evidence to support population screening for oral cancer, although the mouth is easy to examine, and the disease is common in certain parts of the world and/or subsegments of the population. Oral cancer screening programs have been carried out on several hundred thousands of individuals in developing countries (mostly India and Cuba) and several thousands in developed countries (mostly the U.S.A., U.K. and Italy). Especially in developed countries, lesions of the pharynx and larynx were also searched for. Substantial portions of individuals with suspicious lesions (around 10%), mostly leukoplakia, could be identified, but major difficulties were found in targeting highest-risk individuals and referring them to a specialised centre, when necessary. When oral inspection was repeated, relatively high incidence of oral cancer, after removal of prevalent cases, suggested a rather short sojourn time for preclinical cancer (in the order of one year). Oral cancer screening programmes would be greatly facilitated by screening tests able to anticipate the detection of a preclinical phase, compared to visual inspection, thus allowing screening intervals to be prolonged. Finally, even if dysplastic lesions of the oral cavity were better recognised and understood (e.g. as for intra-epithelial lesions of the cervix uteri), surgical control of the disease would be harder than for the uterus, breast, or colon-rectum.

Head and Neck Neoplasms↗

Chromosome 13q deletion mapping in head and neck squamous cell carcinomas: identification of two distinct regions of preferential loss.

Heal and neck squamous cell carcinomas show frequent cytogenetic alterations involving the long arm of chromosome 13. To define the extent of 13q deletions and to identify the minimal areas of chromosome loss, 48 primary squamous cell carcinomas of the head and neck were analyzed for loss of heterozygosity using 11 different polymorphic loci. About 67% of the tumors displayed loss of genetic material at 13q. Most of the cases showed loss of the entire long arm of the chromosome. However, the presence of partial deletions in 10 cases provided evidence of the existence of two preferential sites of chromosome loss at 13q32-ter and 13q14.2-q14.3. The colocalization of the 13q14 minimal region of deletion with the retinoblastoma (RB) gene, which has been proposed as an oncosuppressor in diverse tumor types, prompted us to verify the involvement of this gene in the development of head and neck cancer. No significant variation in RB protein or RB mRNA expression was detected, thus excluding a role for such a gene in the genesis of this type of tumor. Taken together, our data suggest the existence of two new tumor suppressor genes (one close to and one distal to RB), which play a role in the development and/or progression of head and neck squamous cell carcinomas.

Base Sequence↗

Analysis of prognostic factors for recurrence after neck dissection.

OBJECTIVE: To analyze retrospectively several characteristics to verify the existence of further prognostic factors besides those already known for recurrence after neck dissection. DESIGN: From 1976 to 1993, 1 surgeon performed 1097 neck dissections as single surgical events in 705 patients. Radical neck dissection was performed only in the presence of fixed nodes and functional neck dissection in cases with mobile nodes or without detectable nodes (N0). Functional neck dissection was performed on laryngeal or hypopharyngeal N0 tumors without the dissection of the first level. External beam radiotherapy (RT) was performed based on the following conditions: microscopically positive margins of tumor, more than 2 positive nodes without capsular rupture (pN+R-), or capsular rupture (pN+R+). SETTING: Division of Otolaryngology, General Hospital of Pordenone, northeastern Italy. RESULTS: Nodal recurrences were observed in 38 patients (5.4%). Patient sex and age, histological grading and staging of primary tumor, second tumors, number of nodes, type of neck staging, surgeon's experience, type of dissection, alterations to the dissection, number of pN+R-, and postoperative RT were not significantly related to the recurrence. The clinical staging of nodes at greater than N1 and/or fixed; the neck levels IV, V, and multiple levels; previous RT with or without chemotherapy; the absence of a synchronous tumor operation; the assessment of the dissection as less than radical; the overall number of pN+ at 2 or more; and the presence of pN+R+ were related to higher recurrence rates. CONCLUSION: The treatment policy used herein is effective for pN+R-. A more aggressive multidisciplinary approach might be suggested for N2 and N3 and/or fixed nodes; nodes at levels IV, V, or multiple; nodes dissected less than radically; or pN+R+.

Adult↗