Risk of lung cancer in relation to various metrics of smoking history: a case-control study in Montreal.

BACKGROUND: Few epidemiologic findings are as well established as the association between smoking and lung cancer. It is therefore somewhat surprising that there is not yet a clear consensus about the exposure-response relationships between various metrics of smoking and lung cancer risk. In part this is due to heterogeneity of how exposure-response results have been presented and the relative paucity of published results using any particular metric of exposure. The purposes of this study are: to provide new data on smoking-lung cancer associations and to explore the relative impact of different dimensions of smoking history on lung cancer risk. METHODS: Based on a large lung cancer case-control study (1203 cases and 1513 controls) conducted in Montreal in 1996-2000, we estimated the lifetime prevalence of smoking and odds ratios in relation to several smoking metrics, both categorical and continuous based on multivariable unconditional logistic regression. RESULTS: Odds ratios (ORs) for ever vs never smoking were 7.82 among males and 11.76 among females. ORs increased sharply with every metric of smoking examined, more so for duration than for daily intensity. In models using continuous smoking variables, all metrics had strong effects on OR and mutual adjustment among smoking metrics did not noticeably attenuate the OR estimates, indicating that each metric carries some independent risk-related information. Among all the models tested, the one based on a smoking index that integrates several smoking dimensions, provided the best fitting model. Similar patterns were observed for the different histologic types of lung cancer. CONCLUSIONS: This study provides many estimates of exposure-response relationships between smoking and lung cancer; these can be used in future meta-analyses. Irrespective of the histologic type of lung cancer and the smoking metric examined, high levels of smoking led to high levels of risk, for both men and women.

Human papillomavirus testing improves the accuracy of colposcopy in detection of cervical intraepithelial neoplasia.

To assess the performance of human papillomavirus (HPV) testing and colposcopy in detection of cervical pathology. A series of 389 women referred for colposcopy due to an abnormal Pap smear had cervical swabs analyzed for oncogenic (high-risk [HR]) HPV types using Hybrid Capture II (HC2) assay. Loop electrical excision procedure cone biopsy (88%) or colposcopic biopsy (11%) was used as the gold standard. Of the atypical squamous cells of undetermined significance (ASCUS) smears, 48% were positive for HR HPV, as compared to 76.3% of low-grade squamous intraepithelial lesions (LSIL) smears. HR HPV was detected in 66.7% and 90% of patients with cervical intraepithelial neoplasia (CIN) 1 and CIN2 (or higher), respectively. The sensitivity of the Pap smear using an ASCUS threshold in detecting high-grade CIN was 94.5% (95% confidence intervals (CI): 91-97%) and that of colposcopy 98.5% (95% CI: 95-99%). The respective specificities were 30% (95% CI: 17-28%) and 35.6% (CI: 29-42%). HC2 test had comparable sensitivity, 90% (95% CI: 85-93%), but higher specificity, 54.3% (95% CI: 47-61%). Combining HC2 test with Pap increased specificity, 66.7% and 41.3% for ASCUS and LSIL cutoff, respectively. The minor-abnormality threshold together with HC2 increased specificity of colposcopy with no changes in sensitivity. High viral load (>100 relative light unit/positive control) was associated with significant disease. HPV DNA testing improves the accuracy of colposcopy in the detection of high-grade CIN in women with ASCUS or LSIL smears.

Quantitative founder-effect analysis of French Canadian families identifies specific loci contributing to metabolic phenotypes of hypertension.

The Saguenay-Lac St-Jean population of Quebec is relatively isolated and has genealogical records dating to the 17th-century French founders. In 120 extended families with at least one sib pair affected with early-onset hypertension and/or dyslipidemia, we analyzed the genetic determinants of hypertension and related cardiovascular and metabolic conditions. Variance-components linkage analysis revealed 46 loci after 100,000 permutations. The most prominent clusters of overlapping quantitative-trait loci were on chromosomes 1 and 3, a finding supported by principal-components and bivariate analyses. These genetic determinants were further tested by classifying families by use of LOD score density analysis for each measured phenotype at every 5 cM. Our study showed the founder effect over several generations and classes of living individuals. This quantitative genealogical approach supports the notion of the ancestral causality of traits uniquely present and inherited in distinct family classes. With the founder effect, traits determined within population subsets are measurably and quantitatively transmitted through generational lineage, with a precise component contributing to phenotypic variance. These methods should accelerate the uncovering of causal haplotypes in complex diseases such as hypertension and metabolic syndrome.

Epidemiologic correlates of antibody response to human papillomavirus among women at low risk of cervical cancer.

A population at low risk for developing cervical cancer in Southern Brazil was studied to identify the main determinants of serological response to human papillomavirus (HPV). Enzyme-linked immunosorbent assay tests were performed in 976 women to detect serum IgG antibodies against HPV 16 L1 virus-like particles (VLPs) and HPVs 16, 18, 6 and 11 L1 VLPs as a mixture of antigens. Women with four or more sexual partners were more likely to be seropositive than women with one partner (HPV 16 serology odds ratio [OR]=3.06, 95% confidence interval [CI]: 2.0-4.8; HPV 6/11/16/18 serology OR=4.64, 95% CI: 3.0-7.2). HPV DNA and both serological responses were associated. Those positives to HPV 16 serology were twice as likely to have a cytological diagnosis of squamous intraepithelial lesions (SILs) than seronegatives (OR=2.07; 95% CI: 1.0-4.5, and OR=1.73; 95% CI: 0.8-3.8). Seropositivity to HPV 16 and HPV 6/11/16/18 antigens seem to be better markers of past sexual activity than current HPV infection, and humoral response to HPV 16 or HPV 6/11/16/18 may not be a strong indicator of cervical lesions in populations at low risk for cervical lesions.

Flexible chemotherapy regimen with gemcitabine and vinorelbine for metastatic nonsmall cell lung carcinoma: a phase II multicenter trial.

BACKGROUND: This Phase II study evaluated a flexible 3- or 4-week dosing schedule of gemcitabine and vinorelbine to determine its effect on response rate and survival of patients with metastatic nonsmall cell lung carcinoma (NSCLC). METHODS: Thirty-four response-evaluable patients, 24 with performance status (PS) 0-1 and 10 with a PS of 2, 30 with Stage IV, and 4 with Stage IIIB NSCLC were treated with gemcitabine 1000 mg/m(2) intravenously and vinorelbine 25 mg/m(2) intravenously (first 15 patients) or 30 mg/m(2) intravenously (next 19 patients) on Days 1, 8, and 15 of a 4-week cycle, if on Day 15 neutrophils were > or = 1500/uL and platelets > or = 100,000/uL. If chemotherapy could not be administered on Day 15, then Day 22 became Day 1 of the next cycle. RESULTS: When vinorelbine 25 mg/m(2) was given with gemcitabine 1000 mg/m(2), 11 patients received 4-week cycles, 3 patients 3-week cycles, and 1 patient both 3- and 4-week cycles. With vinorelbine 30 mg/m(2) and gemcitabine 1000 mg/m(2), 7 patients received 4-week cycles, 2 patients 3-week cycles, and 10 patients both 3- and 4-week cycles. The partial response rate for 34 patients was 53% (18 patients). Median survival (MS) was 11.1 months, and 1-year survival 50% (17 patients). Patients with PS 0+1 had a MS of 17.5 months compared with patients with PS 2, who had MS of 3.3 months. Patients < 70 years of age had a MS of 18 months, and those >/= 70 years had a MS of 5.5 months. CONCLUSION: This flexible schedule with gemcitabine and vinorelbine enabled optimal dose delivery and suggested excellent efficacy but less toxicity than treatment with platinum regimens.

Effect of type of alcoholic beverage on the risks of upper aerodigestive tract cancers in Brazil.

OBJECTIVES: We investigated the effects of alcohol consumption on the risk of cancers of the upper aerodigestive tract (UADT) in a hospital-based case-control study in Brazil. METHODS: A total of 784 cases of cancers of the mouth, pharynx, and larynx and 1578 non-cancer controls matched on age, gender, hospital area, and admission period provided information on alcohol drinking, smoking, and other characteristics via interview. Using logistic regression, we evaluated the relative risks (RR) of UADT cancer for different beverage types based on cumulative ethanol content exposure and frequency of consumption. RESULTS: Relative to nondrinkers of any alcohol, risks of UADT cancers varied across sites both with increased exposure to ethanol and by alcohol type. RRs at equivalent levels of ethanol consumption were highest for cancers of the mouth for hard liquor (6.9 for > 100 kg lifetime consumption, 95% confidence interval (CI) = 2.8-17.1) and cachaça (4.5 for 101-500 kg, 95% CI = 2.2-9.0). Although RRs increased with frequency of drinks per week, when evaluated against higher proportional alcohol intake, reductions in risk were observed for beer and wine. CONCLUSION: Although methods of measurement can influence the interpretation of the carcinogenic nature of alcohols, increased RRs persisted with continued exposure for all types.

Determinants of low-risk and high-risk cervical human papillomavirus infections in Montreal University students.

BACKGROUND: Previous studies have been inconsistent about the degree of sexual transmissibility of cervical human papillomavirus (HPV) infection. The authors hypothesize that risk factors for HPV infection vary according to HPV type. GOAL: To estimate the prevalence of HPV infection in asymptomatic women and to identify risk factors for overall HPV infection and HPV infection by oncogenic and nononcogenic type. STUDY DESIGN: A cross-sectional survey was conducted at the McGill University clinic in Montreal. Cervical specimens were collected from 489 female students presenting at the clinic for a routine Papanicolaou test. Data on potential risk factors was obtained by questionnaire. Human papillomavirus DNA was detected by the polymerase chain reaction using consensus primers (MY09/11) followed by hybridization with generic and type-specific probes using Southern blot and dot blot techniques. RESULTS: The overall HPV prevalence was 21.8%. A low-risk HPV infection was found in 6.2% of the women, 11.8% had a high-risk HPV infection (types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58), 7.1% had an unknown HPV type, and 2.7% had a multiple type infection. Two profiles emerged for sexual activity and risk of HPV infection according to oncogenic risk after multivariate analysis. Lifetime frequency of sexual intercourse and lifetime number of oral sex partners was associated with high-oncogenic-risk HPV infections; however, HPV infection with low-oncogenic-risk types was invariant with respect to markers of sexual activity. CONCLUSION: These results suggest that there are differences in epidemiologic correlates of transmission between low-risk and high-oncogenic-risk HPV types based on oncogenicity. This finding has important implications for primary prevention of HPV infection and cervical cancer precursors.

Interaction between tobacco and alcohol consumption and the risk of cancers of the upper aero-digestive tract in Brazil.

The authors investigated the joint effects of tobacco and alcohol consumption on the risk of squamous cell carcinomas of the upper aero-digestive tract (UADT) using data from a hospital-based case-control study conducted in southern Brazil, 1986-1989. A total of 784 cases of cancers of the mouth, pharynx, and larynx and 1,578 non-cancer controls matched on age, sex, hospital catchment area, and period of admission were interviewed about their smoking and drinking habits and other characteristics. Using logistic regression, evidence was found for interaction between the cumulative exposures for smoking and alcohol on UADT cancer risk. The joint effects for pharyngeal cancers exceeded the levels expected under a multiplicative model for moderate smokers (p = 0.007). There was little statistical evidence, however, for interaction on cancers of the mouth (p = 0.28) or larynx (p = 0.95). Among never smokers, heavy drinkers had 9.2 times (95% confidence interval 1.7, 48.5) greater risk of cancers of mouth, pharynx, and supraglottis than never drinkers, with a dose-response trend (p = 0.013) with cumulative consumption. The authors conclude that the interaction occurring in the pharynx between smoking and alcohol on UADT cancers is not uniform, with varying effects depending on the level of smoking exposure. Alcohol may act as both a promoter for tobacco and as an independent risk factor.

Effect of smoking cessation and tobacco type on the risk of cancers of the upper aero-digestive tract in Brazil.

Tobacco smoking has long been identified as the most important risk factor for upper aero-digestive tract cancers. To investigate the effect of different tobacco types and the benefit of smoking cessation, we analyzed data from a case-control study of 784 cases of mouth, pharynx, and larynx cancers and 1,578 non-cancer controls in three metropolitan hospital areas in Brazil. Subjects were interviewed as to their smoking and drinking habits, demographics, environmental exposures, occupational history, health characteristics, and diet. Controlling for total tobacco and alcohol consumption, risks for ex-smokers compared with current smokers decreased substantially with time since cessation of the habit. Compared with never smokers, ex-smokers of >20 years had a relative risk (RR) of 1.98 [95% confidence interval (CI) = 1.0-3.8] for all upper aerodigestive tract cancers. RRs for long-term (>20 years) ex-smokers tended to be lower for mouth (RR = 1.61) and pharynx (RR = 1.52) than for larynx (RR = 3.63) cancers. The benefit of quitting was strongest for commercial cigarettes (RR = 1.45, 95% CI = 0.7-3.0) for ex-smokers of >10 years, as compared with smoking of black tobacco (RR = 2.57, 95% CI = 1.4-4.6), cigars (RR = 2.59, 95% CI = 0.6-11.6), and pipe tobacco (RR = 3.40, 95% CI = 1.3-8.8).

Human papillomavirus and prognoses of patients with cancers of the upper aerodigestive tract.

BACKGROUND: Some studies have shown that human papillomavirus (HPV) infection may play not only an etiologic role in anogenital cancers but also a role in the clinical outcome. The objective of the current study was to determine whether detection of HPV DNA in primary squamous cell carcinomas of the upper aerodigestive tract (UADT) is a prognostic factor in patients with the disease. METHODS: The authors analyzed archival specimens of UADT tumors from 101 randomly selected patients with evaluable samples for HPV DNA detection. HPV testing was performed using a general primer-mediated polymerase chain reaction. RESULTS: The overall detection rate was 16.8% (17 of 101 specimens). HPV DNA was detected at higher rates in specimens from younger patients and in well-differentiated tumors. Pharyngeal tumors were more likely to be HPV positive (30.0%) than buccal (10.3%) or laryngeal tumors (15.4%), but the differences were not significant. The detection rate was similar for T1-T2 tumors (17.4%) and T3-T4 tumors (15.6%). However, tumors without lymph node metastasis were more likely to be HPV positive (21.4%) than tumors with lymph node involvement (6.5%). Kaplan-Meier and Cox regression survival analyses did not show any difference in overall or disease free survival according to HPV detection. CONCLUSIONS: Although the HPV DNA detection rate was slightly higher in local than in regionally spread tumors, our results support the hypothesis that it is very unlikely that HPV detection plays any role in the prognoses of patients with UADT squamous cell carcinoma.

Relationship between dental factors and risk of upper aerodigestive tract cancer.

We examined the relationship between dental health variables and risk of upper aerodigestive tract (UADT) cancers in a case-control study in Southern Brazil. The study population included 717 cases of cancers of the mouth, pharynx, and larynx and 1434 controls matched on age, gender, period of admission and study site. The association with dental factors was investigated by conditional logistic regression using extensive adjustment for a priori and empirical confounders, including tobacco and alcohol consumption, diet and sociodemographic variables. Lifetime use of dentures was not associated with risk of any UADT cancer, but history of oral sores secondary to ill-fitting dentures was associated with cancers of the mouth (odds ratio [OR] = 2.3, 95% confidence interval [CI] 1.2-4.6) and of the pharynx (OR = 2.7, 95% CI 1.1-6.2) among those using dentures. The association for mouth cancers was restricted primarily to an increased risk of tongue neoplasms (OR = 9.1, 95% CI 1.9-43.4). Less than daily tooth brushing frequency was also associated with risk of cancer of the tongue (OR = 2.1, 95% CI 1.0-4.3) and of other parts of the mouth (OR = 2.4, 95% CI 1.0-5.4). Having broken teeth was not significantly associated with risk of UADT cancer of any site. We conclude that poor oral hygiene due to infrequent tooth brushing and sores caused by dentures are risk factors for cancer of the mouth and that these associations are unlikely to be due to insufficient control of confounding.

Relationship between dental factors and risk of upper aerodigestive tract cancer / Relação entre os fatores dentais e risco de cancer no trato aero-digestivo alto

We examined the relationship between dental health variables and risk of upper aerodigestive tract (UADT) cancers in a case-control study in Southern Brazil. The study population included 717 cases of cancers of the mouth, pharynx, and larynx and 1434 controls matched on age, gender, period of admission and study site. The association with dental factors was investigated by conditional logistic regression using extensive adjustment for a priori and empirical confounders, including tobacco and alcohol consumption, diet and sociodemographic variables. Lifetime use of dentures was not associated with risk of any UADT cancer, but history of oral sores secondary to ill-fitting dentures was associated with cancers of the mouth (odds ratio [OR] = 2.3, 95 per cent confidence interval [CI] 1.2-4.6) and of the pharynx (OR = 2.7, 95 per cent CI 1.1-6.2) among those using dentures...

Use of wood stoves and risk of cancers of the upper aero-digestive tract: a case-control study.

BACKGROUND: Incidence rates for cancers of the upper aero-digestive tract in Southern Brazil are among the highest in the world. A case-control study was designed to identify the main risk factors for carcinomas of mouth, pharynx, and larynx in the region. We tested the hypothesis of whether use of wood stoves is associated with these cancers. METHODS: Information on known and potential risk factors was obtained from interviews with 784 cases and 1568 non-cancer controls. We estimated the effect of use of wood stove by conditional logistic regression, with adjustment for smoking, alcohol consumption and for other sociodemographic and dietary variables chosen as empirical confounders based on a change-in-estimate criterion. RESULTS: After extensive adjustment for all the empirical confounders the odds ratio (OR) for all upper aero-digestive tract cancers was 2.68 (95% confidence interval [CI] : 2.2-3.3). Increased risks were also seen in site-specific analyses for mouth (OR = 2.73; 95% CI: 1.8-4.2), pharyngeal (OR = 3.82; 95% CI: 2.0-7.4), and laryngeal carcinomas (OR = 2.34; 95% CI: 1.2-4.7). Significant risk elevations remained for each of the three anatomic sites and for all sites combined even after we purposefully biased the analyses towards the null hypothesis by adjusting the effect of wood stove use only for positive empirical confounders. CONCLUSIONS: The association of use of wood stoves with cancers of the upper aero-digestive tract is genuine and unlikely to result from insufficient control of confounding. Due to its high prevalence, use of wood stoves may be linked to as many as 30% of all cancers occurring in the region.

Maté, coffee, and tea consumption and risk of cancers of the upper aerodigestive tract in southern Brazil.

Consumption of maté, a tea-like infusion of the herb Ilex paraguariensis, is common in South America. Drinkers have high risks of upper aerodigestive tract cancers, but it is conceivable that this high risk may be attributable to confounding by smoking alcohol, and other exposures. To test this hypothesis, we analyzed the data from a case-control study of upper aerodigestive tract cancers conducted in Southern Brazil. We matched noncancer controls (N = 756) to cases (N = 378) on the basis of age, sex, and period of admission. We estimated the effect of mateé consumption by conditional logistic regression with adjustment for smoking, alcohol, sociodemographics, and several dietary items, considered as confounders. The unadjusted relative risk (RR) for all upper aerodigestive tract cancers was 2.1 [95% confidence interval (CI) = 1.6-2.7]. Some excess risk persisted after adjustment for potential confounders (RR = 1.6; 95% CI = 1.2-2.2). Most of the excess risk for maté drinkers was for oral (RR = 1.9; 95% CI = 1.1-3.3) and laryngeal (RR = 2.2; 95% CI = 2.2; 95% CI = 1.1-4.5) cancers. There was no evidence of associations with coffee and tea drinking. We conclude that the association of maté consumption with upper aerodigestive tract cancer risk is unlikely to result from insufficient control of confounding by critical exposures. Owing to its high prevalence in Southern South America, maté drinking may be linked to as many as 20% of all cases occurring in this region.

[Ruptured aneurysms of the abdominal aorta. A study of their incidence and mortality]. / Aneurismas rotos de aorta abdominal. Un estudio de la incidencia y mortalidad.

Between 1986 and 1992, 133 patients with abdominal aneurysms presented to our Department of Vascular Surgery. Of these, 97 (73%) were elective cases and 36 (27%) had ruptured. In all these patients resections were undertaken. Postoperative complications occurred in 28 patients (28%) for elective resection and in 17 patients (47%) for ruptured aneurysms (p < 0.05), with mortality rates of 46 and 94%, respectively (p < 0.005). The postoperative mortality for elective resection was 13% and for rupture 44% (p < 0.001).

Prevention of stroke--a report from collaboration project between Zagreb and Barcelona.

Cerebrovascular disease (CVD) is the main killer in the modern society and the most frequent cause of death and disability. According to the experiences of highly developed Western countries, especially of the U.S.A., the incidence of stroke can be reduced by the development and introduction of preventive actions and change of life style. Incidence of cerebrovascular disease is high in Croatia as well as in Spain (46% in the 46-59 age range) with an increasing tendency in younger population. As prevention is the only way of CVD incidence reduction, it is indispensable to organize an integral preventive neurologic network. Within the W.H.O. project "Health for All by the Year 2000 and the project "Zagreb"--Healthy City" a preventive action under the slogan 'With perfect brain and veins--enjoy the healthy days', has been organized with the aim to reduce the incidence of stroke for 20% during the following 10-year period. A standardized work of preventive network in Zagreb has also been established in Barcelona as a joint work. Using the interdisciplinary counselling approach, medical teams are still making examinations. In Zagreb Center for Neurological Sciences and Brain Research, data of risk factor distributions and trends of stroke incidence changes have been collected and the results have been analyzed. The Zagreb Center has also become a center for continuous evaluation and further planning. In this article functions of preventive centers, the preventive standardized protocol and structural and functional preventive network are introduced. The results of preventive action in Zagreb are also briefly presented.

Transcranial Doppler diagnostic criteria in the evaluations of arteriovenous malformations.

In order to get a better insight in hemodynamic occurrence of intracranial arteriovenous malformations (AVM), 31 patients with AVM, documented by CT and angiography, were investigated by Transcranial Doppler (TDC). Although the angiography provides definite diagnosis of AVM, its size, position, type feeders and involvement of various vascular segments, TCD provides more information about collateral circulation, intracerebral shunts or functional stenosis due to high blood velocities within the blood vessels involved by AVM. The parameters obtained by TCD: mean cerebral blood flow velocities (MCBFV) in middle and internal carotid artery (MCA, ICA), pulsatility index (PI), MCA/ICA ratio and (S-D)/S ratio were introduced. Results have shown that TCD findings in non-feeding arteries were normal in all patients. TCD finding of MCBFV in MCA and ICA, PI and MCA/ICA ratio in feeding arteries has shown a significant difference from normal arteries (p less than 0.01). These parameters are shown to be AVM size dependent. MCBFV in MCA on the feeder side was statistically significant higher in those patients with large AVM (greater than 4 cm) size (p less than 0.01). For assessment of AVM and its improved and advanced analysis the potential advantages of parameters: (S-D)/S ratio and 3D hemodynamic mapping has been emphasised.

[Obliteration of the juxtarenal abdominal aorta. 90% stenosis of the left renal artery. Thrombosis of the right renal artery and renal atrophy. Treatment with aortic deobliteration, aorto-bifemoral prosthesis, left aorto-renal bypass and right nephrectomy. A case report]. / Obliteración de aorta abdominal yuxtarrenal. Estenosis 90% de arteria renal izquierda. Trombosis arteria renal derecha y atrofia renal. Tratado con desobliteración aórtica, prótesis aorto-bifemoral, by-pass aorto-renal izquierdo y nefrectomía derecha. Presentación de un caso.

A case report of a juxtarenal abdominal aortic obliteration, associated to a annulated right kidney, a 90% left renal arterial stenosis, hypertension and chronic renal failure is presented. An aortic desobliteration was performed, with a termino-terminal aortobifemoral prosthesis, a left aortorenal by pass and a right nephrectomy. The result was successfully and allowed a satisfactory evolution of its renal failure and hypertension.