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PubMedDate not supplied

Microsatellite instability as biomarker for risk of multiple primary malignancies of the upper aerodigestive tract.

Head and neck cancer (HNC) patients are at high risk of developing second primary tumors of the upper aerodigestive tract and this is a chief cause of death. Genomic instability reflecting the propensity and the susceptibility of the genome to acquire multiple alterations is considered a driving force behind multiple carcinogenesis and the alterations of the length of single repetitive genomic sequences or microsatellite instability (MI), implicating impaired DNA repair mechanisms, and could be a sensitive marker for assessing genomic instability in multiple HNC. To investigate whether a genetic defect(s) involving the mismatch repair system constitutes a risk factor in patients with multiple head and neck cancer, we examined replication errors (RER) at 10 microsatellite loci in 21 primary and 5 second primary cancers in 21 patients with multiple malignancies of the upper aerodigestive tract, in comparison with match-paired primary HNC from patients without multiple malignancies. A RER+ phenotype (alterations at > or =2 loci) was observed at 10 microsatellite alterations on chromosomes 2, 3, 11, 17 in at least one tumor from 15 out of 21 (71.5%) patients with multiple primary cancers but only in 11 tumors from 40 (27.5%) HNC patients with single cancer (P=0.001). A RER+ phenotype was also associated with a positive familial cancer history (P=0.046). Our results suggest that a genetic instability may play an important role in the pathogenesis of multiple primary cancers and that testing for MI in a primary HNC may be useful in detecting patients with high risk for developing multiple malignancies of the upper aerodigestive tract.

Adult↗

PubMed2002

Physiologically based pharmacokinetic modeling of styrene and styrene oxide respiratory-tract dosimetry in rodents and humans.

Styrene (ST) is widely used to manufacture resins, glass-reinforced plastics, and a number of commercially important polymers (Miller et al., 1994). Chronic ST inhalation studies in rodents have demonstrated unique species specificity in the resulting pulmonary toxicity and carcinogenicity. Increased incidences of pulmonary bronchioloalveolar tumors have been observed in mice, but not in rats. No other tumor type was increased significantly in either species. Clara cells lining the respiratory epithelium metabolize ST to styrene 7,8-oxide (SO), which is cytotoxic and weakly genotoxic. Rodent species show marked differences in the distribution and regional density of Clara cells within the respiratory tract, as well as in their capacity to produce and eliminate SO. A mode of action-based physiologically based pharmacokinetic (PBPK) model was developed to predict the concentration of ST and SO in blood, liver, and the respiratory-tract tissues, particularly in terminal bronchioles (target tisue), in order to conduct interspecies extrapolations and determine the extent to which there is a pharmacokinetic basis for the observed species specificity. This PBPK model has a multicompartment description of the respiratory tract and incorporates species-specific quantitative information on respiratory-tract physiology, cellular composition, and metabolic capacity. The model is validated against multiple data sets, including blood, liver, and whole lung tissue concentration of ST and SO following multiple routes of exposure. The trend in neoplastic incidences in mice correlated well with model-estimated SO concentration in the terminal bronchioles. The PBPK model predicts a 10-fold lower SO concentration in the terminal bronchioles in rats compared to mice, which is consistent with the observed species sensitivity to the development of respiratory-tract neoplasms. The model-based analysis suggests that humans would be expected to be 100-fold less sensitive to ST-inducted lung tumors than mice, based on pharmacokinetic differences. Pharmacodynamic factors are also expected to contribute to species sensitivity, potentially augmenting pharmacokinetics-based differences.

Animals↗

PubMed1991

Smoking and cancer with emphasis on Europe.

A summary of smoking and cancer in various European countries is presented Important points are the tobacco/alcohol interaction in the elevated mortality rates from upper digestive and respiratory tract neoplasms in France and other southern European countries, the delay in the lung cancer epidemic in females compared with the situation in North America (with the major exception of the United Kingdom) and the different pattern of lung cancer rates in younger compared with older generations (which suggests that eastern and southern European countries will have the highest lung cancer rates at the beginning of the next century in the absence of urgent intervention). The efficacy of anti-smoking policies in Scandinavian countries which now have the lowest lung cancer rates in Europe and the persisting importance of high-tar dark-tobacco cigarettes in eastern and southern Europe in enhancing the risk not only of cancer of the lung but also of upper digestive and respiratory and bladder neoplasms are also discussed.

Europe↗

PubMed1980

Nickel-related cancers of the respiratory tract.

Nickel-related cancers of the respiratory tract have been recognized for nearly 50 years and represent a unique opportunity for prevention among refinery workers. Studies of exposed employees have been conducted in which evaluations were made of the histopathologic changes in the respiratory mucosa and the body burden of nickel was measured by regular plasma nickel determinations. The sites of tumor predilection are related to airflow patterns of the nose and tracheobronchial tree. The metaplastic changes in these areas are accompanied by increased tissue concentrations of nickel. Close monitoring of nickel workers has led to a lower incidence of respiratory cancers and earlier diagnosis.

Adult↗

PubMed1993

Mucosal melanomas of the upper aerodigestive tract.

Mucosal melanoma of the upper aerodigestive tract is a rare disease with a relentless inexorable course. This lesion involved the nasal cavity, maxillary sinus and palate in two cases each all of whom underwent a radical excision. The disease did not respond to radiotherapy in two patients with nasopharyngeal involvement. One other patient died of distant metastasis within five weeks of diagnosis. Despite surgery offering variable disease free periods, the prognosis remains guarded.

Adult↗

PubMed1982

Socio-economic class differences in cancer incidence in Cali, Colombia.

Based on census tract information, cancer incidence rates for three socio-economic strata of the city of Cali, Colombia, were calculated. Strong negative associations with socio-economic status were found for cancers of the cervix and stomach. Colon cancer and endocrine-related cancers were positively associated with socio-economic status, while no such association was found for rectal cancer. Contrary to data from developed countries, all smoking-related cancers were positively associated with socio-economic class. The role of socio-economic gradients in developing countries is stressed as a basis for etiological research.

Adolescent↗

PubMed1994

Second cancers following oral and pharyngeal cancers: role of tobacco and alcohol.

BACKGROUND: The exceptionally high rate of second primary cancers among patients with oral and pharyngeal cancers is well recognized, yet there has been limited epidemiologic study of risk factors for second tumors. PURPOSE: To evaluate the relation of smoking and alcohol consumption to the development of second cancers among this high-risk patient group, we conducted a nested case-control study. METHODS: A total of 1090 patients enrolled in a 1984-1985 population-based, case-control study of oral cancer in four areas of the United States were followed through June 1989 for the occurrence of second primary cancers. Information on tobacco and alcohol consumption was obtained from the original interviews and was updated by follow-up interviews obtained for 80 case patients with second cancers and 189 sex-, study area-, and survival-matched cancer patients free of second cancers (control subjects). RESULTS: Tobacco smoking and alcohol drinking each contributed to risk of second cancers, with the effects of smoking more pronounced than those of alcohol. The odds ratios (ORs) for smoking (adjusted for alcohol) rose with duration and intensity of smoking and were strongest for tumors of the aerodigestive tract (oral cavity, pharynx, esophagus, larynx, and lungs), with ORs reaching 4.7 (95% confidence interval [CI] = 1.4-16) among smokers of 40 or more cigarettes per day for 20 or more years. Current smokers as of the baseline survey experienced a fourfold increased risk of a second aerodigestive tract cancer relative to nonsmokers and former smokers. No reduction in risk was associated with cessation of smoking or drinking at or after the index diagnosis, although the short median interval (27 months) between tumor diagnoses limited observation of the effects due to recent cessation. Risk was significantly reduced, however, 5 years after smoking cessation. Among drinkers, second cancer risk was greatest for beer intake, with an OR for a second aerodigestive tract cancer of 3.8 (95% CI = 1.2-12) for 15 or more beers per week. CONCLUSIONS: Oral and pharyngeal cancer patients with the highest intakes of tobacco and alcohol are the ones most prone to develop second primary cancers. IMPLICATIONS: Avoidance of tobacco smoking and alcohol drinking is the most desirable way not only to prevent primary oral cancers, but also to reduce risk of second cancers of the aerodigestive system.

Aged↗

PubMed1976

Tobacco and tobacco smoke.

Epidemiologic studies have demonstrated a causal relation between smoking of cigarettes and cancer of the lung in man. Women smokers, cigar, and pipe smokers also face an increased risk for lung cancer. Prospective and retrospective studies have found a correlation between smoking of cigarettes, cigars, and pipes and cancer of the oral cavity, larynx, and esophagus and for cigarette smokers increased risks to develop cancer of the pancreas, kidney, and urinary bladder. Dose responses have been established between number of cigarettes smoked and cancer of the respiratory and upper digestive tract. Tobacco chewers face an increased risk for cancer of the mouth and esophagus. Tobacco smoke has induced tumors of the lung in the dogs and of the larynx of hamsters. The particulate matter of the smoke is carcinogenic to the skin of mice and rabbits, and the bronchi and connective tissue of rats. In tobacco smoke were identified tumor initiators, tumor promoters, cocarcinogens and organ specific carcinogens. Chewing tobacco is a tumor promoting agent and contains traces of tobacco specific and carcinogenic nitrosamines. Ten to 15 yr after giving up smoking the ex-smoker faces the same low risk to develop cancer of the upper digestive tract, the lung, the pancreas, and the urinary tract as the nonsmoker. It should be our goal, therefore, to prevent young people from starting the smoking habit and to convince the smoker to quit smoking. So far, we can report no success in terms of decreasing smoking habits among younger people. On the other hand, we can take satisfaction from the fact that antismoking propaganda has had an effect on college educated males, that among the population as a whole, there is a considerable number of exsmokers; that smoking cessation clinics do prove cost effective and if they were to become part of every health care center, they could help a large number of heavy smokers who cannot seem to stop smoking on their own. We can also report that there has been a significant reduction in the tar yield of American cigarettes, a reduction which we hope will continue; that the tumorigenic activity of tobacco as measured in animal studies, has decreased; and that as a consequence of the above, the risk of lung cancer and other tobacco-related cancers among smokers of these cigarettes is lower than in years past. It is unlikely that man will ever be able to inhale smoke components as harmless as unpolluted air, but as long as we have a society which accepts this habit and as long as people find satisfaction in smoking, we must work towards the day when tobacco-related cancers and other diseases will be reduced to a minimum. With the world wide coperation of the scientific community, the Departments of Agriculture, and the tobacco industry, it is our hope that this goal will be achieved.

Age Factors↗

PubMed1996

"Decadose" effects of cisplatin on squamous cell carcinoma of the upper aerodigestive tract. I. Histoculture experiments.

There is substantial laboratory and clinical evidence that solid tumors rapidly acquire cellular resistance to cisplatin. Experiments with human carcinoma cell lines and clonogenic assays indicate that resistance is usually mild to moderate and can be circumvented with higher concentrations of drug. The purpose of this investigation was to test this hypothesis with a histoculture assay of human upper aerodigestive tract (UADT) carcinomas. Using a sponge-gel supported histoculture, 43 tumor specimens from patients with squamous cell carcinoma (SCC) of the UADT were grown and exposed to cisplatin. Growth inhibition by the drug, in concentrations equivalent to peak therapeutic doses (1.5 micrograms/mL) and concentrations 10 and 25 times greater (15 and 37.5 micrograms/mL), were measured in specimens from patients with previously untreated and recurrent lesions. In vitro, the overall rate of sensitivity of the tumor samples to cisplatin concentrations of 1.5, 15, and 37.5 micrograms/mL were 22%, 62%, and 83%, respectively. In patients with previously untreated disease, the respective rates were 25.9%, 63.3%, and 79.3%, as compared with 10.0%, 55.6%, and 85.6%, respectively, for patients with recurrent disease. The response difference between cisplatin concentrations of 1.5 and 15 micrograms/mL was statistically significant. The "decadose" effect of cisplatin on growth inhibition was 2.44-fold for untreated lesions and 5.56-fold for recurrent tumors. The results indicate that resistance to standard doses of cisplatin by SCC of the UADT can be substantially overcome with a decadose (standard dose x 10) increase and is more pronounced in tumors from patients with recurrent disease. Progress toward improving survival of patients may be possible by incorporating decadose cisplatin therapy into a multimodality treatment plan.

Antineoplastic Agents↗

PubMedDate not supplied

Cancer incidence in Suriname from 1980 through 2000 a descriptive study.

BACKGROUND AND AIMS: Current data on the epidemiology of cancer in the Republic of Suriname are scant and incomplete. In this study, incidence rates of the histopathologically confirmed malignancies in the country from 1980 through 2000 were inventoried. PATIENTS AND METHODS: Numbers of diagnoses, as well as patient information, were acquired from the Pathology Laboratory. The General Bureau of Statistics of Suriname provided relevant demographic information. For each year, crude incidence and sex-specific rates were calculated for: cancer overall; the most frequent cancer sites; age strata 0-19, 20-49, and 50+ years; as well as for the presumably largest, second largest, and third largest ethnic group, viz. the Hindustani, Creole, and Javanese. From these data, average rates were calculated, which were expressed as mean +/- SD per 100,000 population per year, or per 100,000 males or females per year. RESULTS: Average yearly crude and sex-specific incidence rates for cancer overall were 70 +/- 12: 59 +/- 9 for men and 83 +/- 12 for women. The leading cancer sites were cervix uteri (sex-specific rate of 22.1 +/- 5.1) as well as gastrointestinal tract, breast, hematological system, prostate, head and neck, lung, and liver (sex-specific rates ranging from 2 to 17). The relatively high rate of cervical cancer was for an important part responsible for the 1.4-fold female over male overall cancer excess. Incidence rates of most cancers increased from age group 20-49 years on, being highest after age 50+ years, but hematological malignancies occurred in all age groups with rates of 1-3 new cases per 100,000 males or females per year. Cancer was in general 2-6 times more common in Creole than in Hindustani and Javanese. However, cervical cancer was seen as often in Hindustani as in Creole. Most cases of primary liver cancer involved, besides Creole of both genders, Javanese males. Thyroid cancer occurred more frequently in Hindustani women. CONCLUSIONS: The data from the study suggest that the incidence profile of cancer in Suriname may resemble that of most developing countries. It was relatively low for cancer overall as well as for most individual sites, but relatively high for cervical cancer, thus producing the characteristic female over male excess. More detailed studies on the peculiarities in the ethnic distribution of cancer may help to shed more light on the etiology of certain malignancies.

Adolescent↗

PubMed2001

Latex allergy: an update for the otolaryngologist.

OBJECTIVE: To describe the clinical manifestations of latex allergy in otolaryngology patients. DESIGN: Descriptive case series. SETTING: Tertiary academic otolaryngology practice. PATIENTS: Otolaryngology patients with documented allergic reactions to latex during surgery and confirmatory laboratory test results for latex allergy. MAIN OUTCOME MEASURES: Clinical description of latex reactions; identification of risk factors for latex allergy. RESULTS: We describe 3 patients, 2 children and 1 young adult, with severe latex allergy manifested by intraoperative cardiorespiratory changes and confirmed by positive latex-specific IgE test results. A 9-year-old boy with a tracheotomy and a history of multiple procedures for laryngeal stenosis developed a rash and unexplained bronchospasm during an open laryngeal procedure. Surgery was aborted, and subsequent surgery was performed uneventfully 4 weeks later using a latex-safe environment. A 13-year-old boy with recurrent respiratory papillomatosis and a ventriculoperitoneal shunt had sudden unexplained arterial oxygen desaturation and a rash during laser endoscopy. He was then treated successfully using latex-safe protocols. A 23-year-old man with a parotid malignancy developed unexplained hypotension and ventilatory difficulties in the operating room during preparation for surgery. He responded to medical treatment for anaphylaxis. CONCLUSION: The otolaryngologist should share in the increased awareness of latex allergy. Our patients who have had multiple surgical procedures or who are exposed to latex on a long-term basis may be at increased risk. Latex allergy should be considered when unexplained cardiorespiratory compromise occurs during surgery.

Adolescent↗

PubMed1999

Lymphoma at uncommon sites.

Lymphoma can often present in unusual situations. This article provides a comprehensive review of the literature in which both non-Hodgkin's lymphoma and Hodgkin's disease are discussed.

Female↗

PubMed1966