Search PubMed⌕ Search

Biomedical subjects

J Faivre

Publications and source records attributed to J Faivre.

At least 73 records · Page 4Linked to original sources

[How to choose in practice a model to describe the geographic variation of cancer incidence? Example of gastrointestinal cancers from Côte-d'Or].

BACKGROUNDS: In epidemiology, standardized Incidence Ratio (SIR) can have large variance and it is then difficult to distinguish random fluctuations from real spatial variations when describing spatial variations in the rate of cancer. In this context, hierarchical model produce smoothed relative risks estimations helpful for solving this problem. The main advantage of these methods is to combine information of each geographical area with that obtained from prior assumption on the similarity between geographical sub-units. Nevertheless different assumptions produce different geographical maps of incidence of cancer, and the purpose of the present study was the development of a strategy to choose the most satisfactory description of the incidence of digestive cancer in a French department. METHODS: The strategy to choose the most satisfactory geographical map depends on the following criteria: variability between geographical sub-units, auto-correlation, and variability within geographical sub-unit. These criteria have been estimated from observed data for each site of cancer. RESULTS: This strategy was applied to digestive tract cancers diagnosed between 1976 and 1997 in the department of Côte-d'Or, France. High-risk areas were often detected in the urban zone of the department, but without autocorrelation in most cases. CONCLUSION: This strategy permitted to describe cancers in very small areas, avoiding to a large extent the danger of focusing on falsely positive high-risk areas.

Algorithms↗

[A diagnostic strategy for isolated pulmonary nodules less than 2 cm in diameter].

The object of this study is to determine the best diagnostic strategy for isolated pulmonary nodules less than 2 cm in diameter starting from decision analysis. The diagnostic pathway included strategies: 1. Observation with a thoracic tomodensitometry (TDM) every 3 months. 2. Percutaneous needle biopsy. 3. Video-assisted thoracoscopic surgery (VATS) resection. 4. Resection by thoracotomy. Observation was the best strategy for non-smokers in their 40's with a cost of 57-69 Francs per year of life gained. Needle biopsy was the best strategy for a 1 cm nodule in patients of 50 years, smokers and non-smokers (life expectancy 29.38 and 24.44 years). The best strategy for a 2 cm nodule was needle biopsy in 40 year old smokers (life expectancy 34.18 years) and in non-smokers aged 50-60 years with a life expectancy from 20.0 to 28.2 years. VATS was the best strategy for a 1 cm nodule in smokers over the age of 60 for a 2 cm nodule over the age of 50. The costs were 1 811, 3 214, 1 873, 1 811 and 6 093 Francs respectively per year of life gained. During the sensitivity analysis VATS remained the best strategy provided the post-operative mortality remained below 2%. When the risk of malignancy is only moderate needle biopsy may be recommended but when the risk of malignancy is high it is preferable to advise VATS as the method of diagnosis.

Adult↗

Assessing time-by-covariate interactions in relative survival models using restrictive cubic spline functions.

BACKGROUND: The Cox model is widely used in the evaluation of prognostic factors in clinical research. However, in population-based studies, which assess long-term survival of unselected populations, relative-survival models are often considered more appropriate. In both approaches, the validity of proportional hazards hypothesis should be evaluated. METHODS: We propose a new method in which restricted cubic spline functions are employed to model time-by-covariate interactions in relative survival analyses. The method allows investigation of the shape of possible dependence of the covariate effect on time without having to specify a particular functional form. Restricted cubic spline functions allow graphing of such time-by-covariate interactions, to test formally the proportional hazards assumption, and also to test the linearity of the time-by-covariate interaction. RESULTS: Application of our new method to assess mortality in colon cancer provides strong evidence against the proportional hazards hypothesis, which is rejected for all prognostic factors. The results corroborate previous analyses of similar data-sets, suggesting the importance of both modelling of non-proportional hazards and relative survival approach. We also demonstrate the advantages of using restricted cubic spline functions for modelling non-proportional hazards in relative-survival analysis. The results provide new insights in the estimated impact of older age and of period of diagnosis. DISCUSSION: Using restricted cubic splines in a relative survival model allows the representation of both simple and complex patterns of changes in relative risks over time, with a single parsimonious model without a priori assumptions about the functional form of these changes.

Aged↗

Membrane-anchored cyclin A2 triggers Cdc2 activation in Xenopus oocyte.

In Xenopus oocyte, the formation of complexes between neosynthesized cyclins and Cdc2 contributes to Cdc2 kinase activation that triggers meiotic divisions. It has been proposed that cytoplasmic membranes could be involved in this process. To investigate this possibility, we have injected in the oocyte two undegradable human cyclin A2 mutants anchored to the endoplasmic reticulum (ER) membrane. They encode fusion proteins between the truncated cyclin A2-Delta152 and a viral or cellular ER-targeting domain. We show that both mutants are fully functional as mitotic cyclins when expressed in Xenopus oocytes, bind Cdc2 and activate M-phase promoting factor.

Animals↗

Estimation of screening test (Hemoccult) sensitivity in colorectal cancer mass screening.

3 controlled cohorts of mass-screening for colorectal cancer using a biennial faecal occult blood (HemoccultII test on well-defined European populations have demonstrated a 14% to 18% reduction in specific mortality. We aimed to estimate the sensitivity (S) of this HemoccultII test and and also mean sojourn time (MST) from French colorectal mass-screening programme data. 6 biennial screening rounds were performed from 1988 to 1998 in 45 603 individuals aged 45-74 years in Saône-et-Loire (Burgundy, France). The prevalent/incidence ratio was calculated in order to obtain a direct estimate of the product S.MST. The analysis of the proportional incidence and its modelling was used to derive an indirect estimate of S and MST. The product S.MST was higher for males than females and higher for left colon than either the right colon or rectum. The analysis of the proportional incidence confirmed the result for subsites but no other significant differences were found. The sensitivity was estimated at 0.57 and the MST at 2.56 years. This study confirms that the sensitivity of the Hemoccult test is relatively low and that the relatively short sojourn time is in favour of annual screening.

Aged↗

Colorectal adenocarcinoma in patients under 45 years of age: comparison with older patients in a well-defined French population.

PURPOSE: Little is known about colorectal cancer in young patients at a population level, and the behavior, characteristics, and prognosis of such tumors continue to be debated. METHODS: A population-based series of 4,643 new cases of colorectal adenocarcinomas diagnosed between 1976 and 1996 in C te d'Or, France, was used to describe time trends in incidence, predisposing conditions, location, stage, and treatment and to evaluate the prognosis of such tumors in patients under 45 years of age (n = 146). Prognosis was determined using relative survival rates and predictive factors using a multivariate relative survival model. RESULTS: Before the age of 45 years, age-standardized incidence rates were 1.9 per 100,000 in males and 1.4 per 100,000 in females. Incidence rates almost doubled from 1976 to 1982 and from 1983 to 1989 in both genders and stabilized thereafter. The frequency of predisposing conditions was significantly higher before the age of 45 years (11.7 vs. 0.4 percent; P < 0.001). TNM Stage III tumors were more frequent in younger patients, and Stage II tumors were more frequent in older patients. The postoperative mortality rate was lower in the 0-to-44 age group, 2.1 percent, compared with 8.4 percent for the 45-and-over age group (P = 0.004). Five-year relative survival rates were 51.9, 49.2, and 41.4 percent, respectively. In both overall and stage-for-stage comparisons, patients before the age of 45 years had a better survival rate than older patients. Gender and stage at diagnosis were the only independent prognostic factors of survival for young patients. CONCLUSIONS: This study confirms the high frequency of predisposing conditions in young patients and that young age is not a poor prognostic factor for colorectal cancer. This underlines the importance of family screening, aggressive surveillance, and treatment in the young with known predisposing conditions.

Adenocarcinoma↗

Hyperparathyroidism in multiple endocrine neoplasia type I: surgical trends and results of a 256-patient series from Groupe D'etude des Néoplasies Endocriniennes Multiples Study Group.

The French and Belgian GENEM study group's multiple endocrine neoplasia type I (MEN-I) database was used to evaluate trends in clinical presentation, surgical treatment of primary hyperparathyroidism (pHPT) (n = 245), and prognostic factors for hypercalcemia correction among 256 MEN-I cases. The patients were retrieved through the GENEM network from various Belgian and French institutions with the help of genetics laboratories. Among the 245 pHPT patients (96%), 42% were men. The mean age at the time of diagnosis was 39.5 +/- 13.3 years. Trends were studied for three periods: before 1986, from 1986 to 1990, and thereafter. After 1990 MEN-I patients were more often diagnosed with isolated pHPT (8%, 11%, 28%, for the three periods, respectively; p = 0.002); it was seen more often in screened patients (31%, 28%, 53%; p = 0.001), more often among those in already known MEN-I families (64%, 45%, 72%; p = 0.005), and among those with lower preoperative calcemia (2.93, 2.87, 2.79 mmol/L; p = 0.001). The age at pHPT diagnosis remained constant throughout the study. The percentage of cervical explorations dropped during the entire study (87%, 87%, 53%; p < 0.0001). After 1985 the percentage of subtotal parathyroidectomies increased (25%, 59%, 51%; p = 0.0004). Pathology disclosed more hyperplasias (59%, 85%, 74%; p = 0.008). Postoperative hypercalcemia decreased (47%, 15%, 19%; p < 0.0001); and postoperative hypocalcemia increased nonsignificantly (5%, 15%, 15%; p = 0.1). Subtotal parathyroidectomy [odds ratio (OR) 13], no MEN-I family background (OR 3), and the most recent study period (> 1985) (OR 3) were significant predictive factors of hypercalcemia correction according to the multivariate analysis. This is the first multicentric study on the management of MEN-I-related pHPT. Immediate postoperative hHPT cure increased, but only 80% of the operated patients were cured after 1990. Fifteen percent were hypocalcemic. Because MEN-I-related hHPT cure remains difficult to achieve, we advocate that subtotal parathyroidectomies be performed in specialized centers.

Adult↗

[Local excision with postoperative radiotherapy for T2 or T3 distal rectal cancer. Long-term results].

STUDY AIM: To evaluate, in a prospective study of a cohort of patients, the local recurrence rate of T2 or T3 rectal cancers treated by transanal excision after preoperative irradiation. PATIENTS AND METHODS: Between 1992 and 1999, 34 patients were treated after radiotherapy by a local excision for a distal rectal carcinoma limited to (stage T2) or invading through the muscular layer (stage T3). Four patients were excluded either for palliative treatment or lost for follow-up. Thirty patients were included in the study (8 uT2, 8 uT3, 14 undetermined preirradiation stage). RESULTS: After a 74-month mean follow-up (median: 46), the 5-year local recurrence rate was 33%. Even among subgroups of patients with a significant risk factor for local recurrence (size > 40 mm, clear margin < 2 mm, uT3 stage versus uT2) there were no benefits from irradiation. CONCLUSION: Local excision of T2 or T3 rectal cancers is associated with an elevated local recurrence rate. This result is demonstrated even after adjunction of a preoperative irradiation. So, local treatment must be restricted to clearly informed patients who definitively refuse a radical intervention.

Aged↗

[Expression of p21 WAF1/CIP1 protein in colorectal cancers: study of its relation to p53 mutation and Ki67 antigen expression].

Mutations of the p53 gene are the most common genetic alteration in malignant human tumors. A cyclin-dependent kinase inhibitor, p21WAF1/CIP1, is thought to be an important mediator of p53-induced cell cycle arrest. Although numerous studies have reported p53 expression and mutation in colorectal cancer few of them have correlated p53 expression with that of its downstream effector p21 and with the proliferation index as measured by expression of the Ki67 nuclear antigen. We studied p53, p21 and Ki67 expression by immunohistochemistry and molecular biology in 35 colorectal carcinomas. We compared these findings with each other and with clinical factors. Sixty three percent of tumors expressed p53 whereas seventy one percent expressed p21WAF1/CIP1. In adenocarcinomas, p21 staining was heterogeneous: p21-reactive cells were seen in the most differentiated areas. There was no correlation between p21WAF1/CIP1 and p53 expression, p53 mutation, Ki67 expression or clinical factors such as sex or location of the tumor. On the other hand, there was a statistical relationship between p21 expression and survival: our results indicated an association between high p21 expression and lower stages p21WAF1/CIP1 appears to be induced independently of p53 in these tumors and may be associated with differentiation rather than proliferation.

Adenocarcinoma↗

Modelling time-dependent hazard ratios in relative survival: application to colon cancer.

The Cox model is widely used in the evaluation of prognostic factors in clinical research. In population-based studies, however, which assess long-term survival of unselected populations, relative survival models are often considered more appropriate. In both approaches, the validity of proportional hazard hypothesis should be evaluated. To explore the validity of the proportional hazard assumption in a population-based study of colon cancer, to propose non-proportional hazard relative survival models and to evaluate their utility. The use of a piecewise proportional hazard relative survival model in colon cancer has shown that the effects of most clinical prognostic factors such as age, period of diagnosis and stage are non-proportional. The non-proportional hazard relative survival models developed in this article have been found to be efficient tools for better understanding the time-dependent aspect of prognostic factors.

Aged↗

Estimation of colorectal cancer prevalence in France.

The prevalence in France of patients with colorectal cancer was estimated using data from five population-based cancer registries. At the end of 1994, the number of cases diagnosed in France no more than 5 years before was approximately 95000, of whom 12180 had suffered metastasis and 9746 a local recurrence. This type of cancer is the most common in both men and women and these results enable the need for care or surveillance to be evaluated more accurately.

Adult↗

Cancer survival increases in Europe, but international differences remain wide.

The EUROCARE project analysed cancer survival data from 45 population-based cancer registries in 17 European countries, revealing wide international differences in cancer survival. We calculated 5-year relative survival for 1836287 patients diagnosed with one of 13 cancers during the period 1978-1989. The data, from 20 cancer registries in 13 countries, were grouped into four regions: Finland, Sweden, Iceland (Northern Europe); Denmark, England and Scotland (UK and Denmark); France, The Netherlands, Germany, Italy and Switzerland (Western Europe); Estonia and Poland (Eastern Europe), and broken down into four periods (1978-1980, 1981-1983, 1984-1986, 1987-1989). For each cancer, mean European and regional survival was estimated as the weighted mean of 5-year relative survival in each country. Survival increased with time for all tumours, particularly for cancers of testis (12% increase, i.e. from 79.9 to 91.9%), breast, large bowel, skin melanoma (approximately 9-10%), and lymphomas (approximately 7%). For most solid tumours, survival was highest in Northern Europe and lowest in Eastern Europe, and also low in the UK and Denmark. Regional variation was less marked for the lymphomas. Survival improved more in Western than Northern Europe, and the differences between these regions fell for bowel cancer (from 8.0% for those diagnosed in 1978-1980 to 2% for those diagnosed in 1987-1989), breast cancer (from 7.4% to 3.9%), skin melanoma (from 13.4% to 11.0%) and Hodgkin's disease (from 7.2 to 0.6%). For potentially curable malignancies such as Hodgkin's disease, large bowel, breast and testicular cancers, there were substantial increases in survival, suggesting an earlier diagnosis and more effective treatment. The persisting regional differences suggest there are corresponding differences in the availability of diagnostic and therapeutic facilities, and in the effectiveness of healthcare systems.

Adolescent↗

Cancer prone persons. A randomized screening trial based on colonoscopy: background, design and recruitment.

OBJECTIVE: Evidence-based counseling and prevention are not available so far for hereditary cancer prone persons, since we lack data based on clinical trials. There are very few high-risk persons in the population as a whole. Based on a familial history analysis, only 1.2% of all healthy volunteers attending screening centers reached the arbitrary high-risk level defined as a Relative Risk of more than 4. We describe a randomized trial based on colonoscopic screening for colorectal cancer on a sub-group of high-risk group persons. MATERIALS AND METHODS: Among the 77 members of the French Institutional Preventive Center Network, 37 took part in this protocol. During the first 3 years, 850,000 persons were interviewed at these 37 Health centers. The enrollment process was particularly time-consuming, since a large amount of information had to be delivered to the participants. RESULTS: The mean rate of recruitment of eligible candidates was far lower than predicted, averaging only 1.4 per 1,000 persons interviewed instead of the 9/1,000 expected. This mean figure was based, however, on inclusion rates ranging from 0.06/1,000 to 7/1,000 among the different centers. The low rates of recruitment were mainly due to the inter-center heterogeneity (differences in commitment and in the resources), and to the fact that the acceptability of undergoing a colonoscopy turned out to be lower than predicted. CONCLUSION: Population trials on cancer prone persons are feasible, but vast numbers have to be pre- screened to identify the few people with a high hereditary risk and willing to accept screening within a controlled trial.

Adolescent↗

Population-based study of factors influencing occurrence and prognosis of local recurrence after surgery for rectal cancer.

BACKGROUND: Few data are available from population-based statistics on the risk of local recurrence after surgery for rectal cancer. The aims of this study were to determine factors influencing local control and to analyse treatment and prognosis of recurrences in a well defined population. METHODS: Data were obtained from the cancer registry of the Côte d'Or (France). From 1976 to 1995, 682 patients resected for cure for a rectal carcinoma were included. Recurrence rates and survival rates were calculated using actuarial methods. A relative survival analysis and Cox multivariate analysis were performed. RESULTS: During the study 135 local recurrences were registered. The 5-year cumulative local recurrence rate was 22.7 per cent. In multivariate analysis the two variables significantly associated with local recurrence risk were stage at diagnosis and the macroscopic type of growth. There was a non-significant decrease in local recurrence rate in patients treated by preoperative radiotherapy compared with that in patients treated by surgery alone. The proportion of patients re-resected for cure was 25.2 per cent, and increased from 13.0 per cent in 1976-1985 to 37.9 per cent in 1986-1995 (P = 0.001). The 5-year relative survival rate was 13.6 per cent overall and 40.6 per cent after resection for cure (P < 0.001). CONCLUSION: Local recurrence of rectal cancer following resection remains a substantial problem. Improvement can be expected from better care and earlier diagnosis.

Adult↗

Energy intake, body mass index, physical activity, and the colorectal adenoma-carcinoma sequence.

Little is known about the precise relationship between energy intake, overweight, sedentary lifestyle, and steps in the colorectal adenoma-carcinoma pathway. We studied these parameters within a case-control study. Patients with adenomas < 10 mm (n = 154) or > 10 mm (n = 208) were compared with polyp-free controls (n = 426) for determining factors associated with adenoma formation, i.e., observed for small and large adenomas, or with adenoma growth only. Colorectal cancer cases (n = 171) were compared with population controls (n = 309) to determine factors specific to the final stage, cancer. Exercise reduced the risk of cancer [odds ratio (OR) = 0.3, 95% confidence interval (CI) = 0.2-0.5 for high vs. low physical activity] but had little influence on adenomas. High energy intake increased the risk of cancer [OR for 5th vs. 1st quintile (OR5) = 1.6, 95% CI = 0.9-2.9, p = 0.02], but not of adenomas. High body mass index (BMI) significantly increased the risk of large adenomas (OR5 = 2.1, 95% CI = 1.2-3.5, p = 0.02 and OR5 = 1.7, 95% CI = 1.0-3.1, p = 0.25) for large and small adenomas vs. polyp-free controls. Neither height nor weight nor BMI influenced the risk of cancer. Results were unmodified when controlling for dietary risk factors and family history. Energy intake, a sedentary lifestyle, and high BMI were independently associated with a high risk of cancer itself or large adenomas, which indicates an effect on promotion of colorectal tumors. These findings suggest that preventive advice regarding these factors should be provided, even late in life, to decrease the risk of colorectal cancer.

Adenoma↗