[Cost of multiple sclerosis in France]. / Coûts de la sclérose en plaques en France.

Multiple sclerosis (MS) is one of the 30 chronic conditions specifically listed by the French healthcare system as a long-term disease (affections de longue durée [ALD]) for which the main health insurance fund (Caisse nationale d'assurance maladie des travailleurs salariés [CNAMTS]) provides full (100%) coverage of healthcare costs. The CNAMTS insures 87% of the French population (52,359,912 of the 60,028,292 inhabitants). The objectives of this study were to evaluate the direct and indirect medical costs of MS among the entire population insured by the CNAMTS in France in 2004. The CNAMTS provided us with access to the ALD database of patients with MS that contains different MS-related expenditures made in 2004. We calculated the overall direct and indirect cost of MS and the cost per patient and per item of expenditure. In 2004, 49,413 patients were registered on the ALD list for MS. Direct cost for MS patients was 469,719,967 €. The direct cost per patient and per year was 9,506 € with variations between regions (French administrative divisions) ranging from 10,800 € in northeastern France (Champagne-Ardenne) to 8,217 € in western France (Pays de la Loire). The different items of expenditure were treatments (44.5%), hospitalization (27.9%), nursing care (5.8%), physiotherapy (5.7%), transport (4%), biology (1.1%), and other (1.5%). During the course of the disease, the overall cost of MS increased slowly during the first 15 years (from 8,000 to 11,000 €), but dramatically the last year of life (23,410 €). The costs of immunomodulator treatments were higher during the first six years after registration on the ALD list. Conversely, physiotherapy costs increased linearly with time during the course of MS. Indirect costs were an estimated 116 million euros in 2004. A disability pension (8,918 € per patient) was perceived by 9,430 patients (19.1%) and a daily allowance (3,317 € per patient) by 9,894 patients (20%). In France, MS has an important economic impact, comparable to human immunodeficiency virus infection.

Heparin-associated thrombocytopenia in 24,401 patients with venous thromboembolism: findings from the RIETE Registry.

BACKGROUND: Whether the treatment of venous thromboembolism (VTE) with unfractionated heparin (UFH) confers a higher risk of thrombocytopenia than does treatment with low molecular weight heparin (LMWH) remains controversial, and very few data are available from routine clinical practice. OBJECTIVES: We assessed the incidence, risk factors and prognosis of heparin-associated thrombocytopenia (HAT) according to the type of heparin therapy, UFH or LMWH. PATIENTS/METHODS: Data were obtained from the international prospective Registro Informatizado de la Enfermedad TromboEmbolica venosa (RIETE), which included 25,369 patients with confirmed VTE until February 2009. Among them, 24,401 patients were treated either with UFH or with LMWH, and had available information about the 6-month occurrence of confirmed thrombocytopenia, defined as a platelet count ≤ 150,000 mm(-3) . RESULTS: One hundred and forty-one patients receiving UFH and/or LMWH developed thrombocytopenia within a 6-month period. The incidence of HAT was significantly higher in the UFH group (1.36%, 95% confidence interval [CI] 0.79-2.17) than in the LMWH group (0.54%, 95% CI 0.44-0.64). As compared with LMWH, UFH significantly increased the risk of HAT in female patients (adjusted hazard ratio [HR] 4.90%, 95% CI 2.58-9.31, P = 0.001) but not in male patients (adjusted HR 1.60%, 95% CI 0.64-3.97, P = 0.31); P = 0.027 for comparison. In each gender, the UFH-associated excess risk was confined to patients with VTE unrelated to cancer. The poor prognosis of patients with thrombocytopenia was not influenced by the type of heparin therapy. CONCLUSIONS: In routine clinical practice, treatment of VTE with UFH seems to confer a higher risk of thrombocytopenia than does treatment with LMWH, especially in women and non-cancerous patients.

Gender-related differences in MEN1 lesion occurrence and diagnosis: a cohort study of 734 cases from the Groupe d'etude des Tumeurs Endocrines.

CONTEXT: Multiple endocrine neoplasia type 1 (MEN1) disease is an autosomal dominant syndrome that is believed to equally affect men and women. This assumption has never been confirmed. OBJECTIVE: The aims of this study were to evaluate the impact of gender on the prevalence of MEN1 lesions, on their lifetime probability of occurrence, and on the diagnosis of MEN1. DESIGN: Data regarding a study of 734 cases of MEN1 from the multicenter 'Groupe d'étude des Tumeurs Endocrines' were analyzed. RESULTS: There were 57.8% females. The prevalence and probability of pancreatic tumors were higher in males than in females (P=0.06, P=0.0004). This difference was due to gastrinomas. The prevalence and probability of developing pituitary tumors were significantly greater in females (P<0.001, P<0.0001). Thymic tumors were exclusively found in men. There were no significant gender differences in the prevalence and the probability of developing hyperparathyroidism, or adrenal and bronchial tumors, or in the proportion of positive genetic tests. A family history of MEN1 was more frequently found in men than in women at the time of diagnosis (P=0.02). In the case of pituitary tumor, the proportion of patients diagnosed with MEN1 at the time of the first lesion was lower in women (44.2%) than in men (67.3%). CONCLUSION: The phenotype expression of the MEN1 disease gene was different in males and females. In female patients, the possibility of MEN1 is not sufficiently taken into account. Any patient presenting a lesion that belongs to the MEN1 spectrum, such as a pituitary tumor, should be closely questioned about their family history and should be tested for hypercalcemia.

Abdominal and pelvic injuries caused by road traffic accidents: characteristics and outcomes in a French cohort of 2,009 casualties.

BACKGROUND: The frequency, characteristics, and effect on outcome of abdominal and pelvic injuries (API) caused by road traffic accidents are not well known. We studied them in a well-defined geographical area in France. METHODS: The medical data of all hospitalized victims of road traffic accidents that occurred over a 3-year period were recorded. Injuries were coded according to the Abbreviated Injury Scale (AIS). The Injury Severity Score (ISS) was calculated. Continuous and qualitative variables were described by means and standard deviations or medians and percentages, respectively. Proportions and means were compared using the χ2 and Student tests, respectively. RESULTS: Of 6,977 victims of road traffic accidents, 2,009 were hospitalized (mean ISS=7.9). API were present in 9.3% (n=186) of all hospitalized victims and in 32.2% (n=82) of the most severely injured (ISS≥16, n=255) hospitalized victims. The most frequently seriously injured abdominopelvic organs (AIS≥3) were the spleen, the retroperitoneal organs, and the liver. The mean ISS and the mortality rate were significantly higher for victims with API than those without API (17.5 vs. 6.9, P<0.001; 9.7% vs. 1.9%, P<0.001). In multivariate analysis, the presence of severe API increased the mortality rate by a factor of 2.5. CONCLUSIONS: In this study, API were present in one third of the most severely injured victims of road traffic accidents and were a significant factor of gravity and mortality. This study, conducted in France where there is no National Trauma Registry, underlined the need for establishing such registry.

The very low penetrance of cystic fibrosis for the R117H mutation: a reappraisal for genetic counselling and newborn screening.

BACKGROUND: Cystic fibrosis (CF) is caused by compound heterozygosity or homozygosity of CF transmembrane conductance regulator gene (CFTR) mutations. Phenotypic variability associated with certain mutations makes genetic counselling difficult, notably for R117H, whose disease phenotype varies from asymptomatic to classical CF. The high frequency of R117H observed in CF newborn screening has also introduced diagnostic dilemmas. The aim of this study was to evaluate the disease penetrance for R117H in order to improve clinical practice. METHODS: The phenotypes in all individuals identified in France as compound heterozygous for R117H and F508del, the most frequent CF mutation, were described. The allelic prevalences of R117H (p(R117H)), on either intron 8 T5 or T7 background, and F508del (p(F508del)) were determined in the French population, to permit an evaluation of the penetrance of CF for the [R117H]+[F508del] genotype. RESULTS: Clinical details were documented for 184 [R117H]+[F508del] individuals, including 72 newborns. The disease phenotype was predominantly mild; one child had classical CF, and three adults' severe pulmonary symptoms. In 5245 healthy adults, p(F508del) was 1.06%, p(R117H;T7) 0.27% and p(R117H;T5)<0.01%. The theoretical number of [R117H;T7]+[F508del] individuals in the French population was estimated at 3650, whereas only 112 were known with CF related symptoms (3.1%). The penetrance of classical CF for [R117H;T7]+[F508del] was estimated at 0.03% and that of severe CF in adulthood at 0.06%. CONCLUSIONS: These results suggest that R117H should be withdrawn from CF mutation panels used for screening programmes. The real impact of so-called disease mutations should be assessed before including them in newborn or preconceptional carrier screening programmes.

Pathogenic FBN1 mutations in 146 adults not meeting clinical diagnostic criteria for Marfan syndrome: further delineation of type 1 fibrillinopathies and focus on patients with an isolated major criterion.

Mutations in the FBN1 gene cause Marfan syndrome (MFS) and have been associated with a wide range of milder overlapping phenotypes. A proportion of patients carrying a FBN1 mutation does not meet diagnostic criteria for MFS, and are diagnosed with "other type I fibrillinopathy." In order to better describe this entity, we analyzed a subgroup of 146 out of 689 adult propositi with incomplete "clinical" international criteria (Ghent nosology) from a large collaborative international study including 1,009 propositi with a pathogenic FBN1 mutation. We focused on patients with only one major clinical criterion, [including isolated ectopia lentis (EL; 12 patients), isolated ascending aortic dilatation (17 patients), and isolated major skeletal manifestations (1 patient)] or with no major criterion but only minor criteria in 1 or more organ systems (16 patients). At least one component of the Ghent nosology, insufficient alone to make a minor criterion, was found in the majority of patients with isolated ascending aortic dilatation and isolated EL. In patients with isolated EL, missense mutations involving a cysteine were predominant, mutations in exons 24-32 were underrepresented, and no mutations leading to a premature truncation were found. Studies of recurrent mutations and affected family members of propositi with only one major clinical criterion argue for a clinical continuum between such phenotypes and classical MFS. Using strict definitions, we conclude that patients with FBN1 mutation and only one major clinical criterion or with only minor clinical criteria of one or more organ system do exist but represent only 5% of the adult cohort.

Empirical study of the dependence of the results of multivariable flexible survival analyses on model selection strategy.

Flexible survival models, which avoid assumptions about hazards proportionality (PH) or linearity of continuous covariates effects, bring the issues of model selection to a new level of complexity. Each 'candidate covariate' requires inter-dependent decisions regarding (i) its inclusion in the model, and representation of its effects on the log hazard as (ii) either constant over time or time-dependent (TD) and, for continuous covariates, (iii) either loglinear or non-loglinear (NL). Moreover, 'optimal' decisions for one covariate depend on the decisions regarding others. Thus, some efficient model-building strategy is necessary.We carried out an empirical study of the impact of the model selection strategy on the estimates obtained in flexible multivariable survival analyses of prognostic factors for mortality in 273 gastric cancer patients. We used 10 different strategies to select alternative multivariable parametric as well as spline-based models, allowing flexible modeling of non-parametric (TD and/or NL) effects. We employed 5-fold cross-validation to compare the predictive ability of alternative models.All flexible models indicated significant non-linearity and changes over time in the effect of age at diagnosis. Conventional 'parametric' models suggested the lack of period effect, whereas more flexible strategies indicated a significant NL effect. Cross-validation confirmed that flexible models predicted better mortality. The resulting differences in the 'final model' selected by various strategies had also impact on the risk prediction for individual subjects.Overall, our analyses underline (a) the importance of accounting for significant non-parametric effects of covariates and (b) the need for developing accurate model selection strategies for flexible survival analyses.

Contribution of molecular analyses in diagnosing Marfan syndrome and type I fibrillinopathies: an international study of 1009 probands.

BACKGROUND: The diagnosis of Marfan syndrome (MFS) is usually initially based on clinical criteria according to the number of major and minor systems affected following international nosology. The number of FBN1 mutation carriers, at risk of aortic complications who would not be properly diagnosed based only on clinical grounds, is of growing importance owing to the increased availability of molecular screening. The aim of the study was to identify patients who should be considered for FBN1 mutation screening. METHODS: Our international series included 1009 probands with a known FBN1 mutation. Patients were classified as either fulfilling or not fulfilling "clinical" criteria. In patients with unfulfilled "clinical" criteria, we evaluated the percentage of additional patients who became positive for international criteria when the FBN1 mutation was considered. The aortic risk was evaluated and compared in patients fulfilling or not fulfilling the "clinical" international criteria. RESULTS: Diagnosis of MFS was possible on clinical grounds in 79% of the adults, whereas 90% fulfilled the international criteria when including the FBN1 mutation. Corresponding figures for children were 56% and 85%, respectively. Aortic dilatation occurred later in adults with unfulfilled "clinical criteria" when compared to the Marfan syndrome group (44% vs 73% at 40 years, p<0.001), but the lifelong risk for ascending aortic dissection or surgery was not significantly different in both groups. CONCLUSIONS: Because of its implications for aortic follow-up, FBN1 molecular analysis is recommended in newly suspected MFS when two systems are involved with at least one major system affected. This is of utmost importance in patients without aortic dilatation and in children.

Time trends in first-diagnosis rates of colorectal adenomas: a 24-year population-based study.

BACKGROUND: Little is known about the descriptive epidemiology of colorectal adenomas diagnosed in the population. AIM: To describe time trends in the rate of first diagnosis of colorectal adenomas and estimate the proportion of adenoma-bearing individuals detected over a 24-year period. METHODS: A total of 11,027 patients were first-diagnosed with colorectal adenomas among Côte-d'Or residents (France) between 1976 and 1999. Annual percentage changes were estimated using a Poisson regression model. The proportion of diagnosed adenoma-bearing individuals was estimated using the prevalence of adenomas in an autopsy study performed in the area. RESULTS: Standardized diagnosis rates were 89.6/100,000 men and 50.3/100,000 women. During the period 1976-1993, diagnosis rates significantly increased with annual percentage changes in men and women of respectively +17.1% and +22.3% for proximal adenomas, +7.5% and +9.1% for distal adenomas and +7.2% and +8.0% for advanced adenomas. Changes were less marked during the period 1994-1999. The estimated proportion of adenoma-bearing individuals diagnosed during the 24-year period was 20.0% in men and 16.0% in women. CONCLUSION: Despite a marked increase in the rate of first adenoma diagnosis, the proportion of diagnosed adenoma-bearing individuals seems too low to induce a significant decrease in colorectal cancer incidence.

Effect of mutation type and location on clinical outcome in 1,013 probands with Marfan syndrome or related phenotypes and FBN1 mutations: an international study.

Mutations in the fibrillin-1 (FBN1) gene cause Marfan syndrome (MFS) and have been associated with a wide range of overlapping phenotypes. Clinical care is complicated by variable age at onset and the wide range of severity of aortic features. The factors that modulate phenotypical severity, both among and within families, remain to be determined. The availability of international FBN1 mutation Universal Mutation Database (UMD-FBN1) has allowed us to perform the largest collaborative study ever reported, to investigate the correlation between the FBN1 genotype and the nature and severity of the clinical phenotype. A range of qualitative and quantitative clinical parameters (skeletal, cardiovascular, ophthalmologic, skin, pulmonary, and dural) was compared for different classes of mutation (types and locations) in 1,013 probands with a pathogenic FBN1 mutation. A higher probability of ectopia lentis was found for patients with a missense mutation substituting or producing a cysteine, when compared with other missense mutations. Patients with an FBN1 premature termination codon had a more severe skeletal and skin phenotype than did patients with an inframe mutation. Mutations in exons 24-32 were associated with a more severe and complete phenotype, including younger age at diagnosis of type I fibrillinopathy and higher probability of developing ectopia lentis, ascending aortic dilatation, aortic surgery, mitral valve abnormalities, scoliosis, and shorter survival; the majority of these results were replicated even when cases of neonatal MFS were excluded. These correlations, found between different mutation types and clinical manifestations, might be explained by different underlying genetic mechanisms (dominant negative versus haploinsufficiency) and by consideration of the two main physiological functions of fibrillin-1 (structural versus mediator of TGF beta signalling). Exon 24-32 mutations define a high-risk group for cardiac manifestations associated with severe prognosis at all ages.

Low compliance with colonoscopic screening in first-degree relatives of patients with large adenomas.

BACKGROUND: Little is known about compliance with colonoscopy as a screening method in first-degree relatives of patients with large adenomas. Aims To evaluate the compliance with screening colonoscopy among this population, and its determinants. METHODS: Data were obtained from the family part of the GEADE study, a study on genetic factors of colorectal adenomas. Index cases were 306 patients with adenomas > or = 10 mm. All living first-degree relatives aged 40-75 who could be contacted by the index case were asked to undergo a colonoscopy, unless they had had one in the previous 5 years. RESULTS: Among 674 eligible relatives, 56 had had a colonoscopy within the preceding 5 years and 114 underwent a screening colonoscopy resulting in a compliance with screening colonoscopy of 18%. This was not related to most characteristics of index cases. Compliance was significantly lower when the index case lived in the Greater Paris area than when he/she lived in other areas (12% vs. 21%). It was higher in siblings (18%) and offspring (23%) than in parents (9%) and in relatives under 55 years old (22%) than in relatives aged 55 and over (15%). CONCLUSIONS: Compliance with colonoscopy was low in first-degree relatives of patients with large adenomas. The reasons for this should be determined and appropriate strategies developed to increase compliance.

Is the management of hepatitis C patients appropriate? A population-based study.

BACKGROUND: In order for hepatitis C patients to receive antiviral treatment, they must reach medical care. AIM: To assess the proportion of patients reaching medical care after hepatitis C diagnosis in a general population (1 006 171 inhabitants) in France. METHODS: Between 1994 and 1999, 1508 cases were diagnosed, of which 1251 were eligible for the study. RESULTS: Two-hundred and two patients did not have any medical care; among them, 55.4% had normal alanine transferase, 58.4% had risk factors related to lifestyle and 22.8% were alcoholics. Amongst the 1049 other patients, 41.6% had a liver biopsy, 25.0% were treated. Treatment was more often carried out in males than in females (OR: 1.59; P = 0.001), and in patients under 65 than in older patients (OR: 2.22; P < 0.008). Among non-treatment reasons, alcoholism (P = 0.001), drug-addiction (P = 0.04) and escaping monitoring (P = 0.04) were more frequent in males than in females, whereas normal alanine transferase was more frequent in females than in males (P = 0.004). Amongst 278 patients with a Metavir score >A1F1, 71 (25.5%) did not undergo treatment. CONCLUSION: In a general population, one patient in six did not receive on-going health care; a quarter of patients with a Metavir score >A1F1 did not receive any treatment. These results showed insufficient clinical management, which could compromise the effectiveness of treatment in general population.

Time trends in the treatment and survival of recurrences from colorectal cancer.

BACKGROUND: Little is known about the management of recurrences from colorectal cancer at a population level. MATERIALS AND METHODS: Data was obtained from the population-based cancer registry of Cote d'Or (Burgundy, France) over a 28-year period. Univariate and multivariate analyses were performed to analyse trends in treatment and survival for local recurrence and distant metastases. RESULTS: The proportion of patients resected for cure increased from 6.7% (1976-1984) to 23.7% (1994-2003; P <0.001) for distant metastases and from 15.9% to 58.1% (P <0.001) for local recurrence. Age and period of diagnosis were independent factors associated with a resection for cure. Rectal cancer local recurrence was less often resected for cure than colon cancer local recurrence (P=0.05). Long-term survival was observed only after resection for cure: 5-year relative survival rates were 36.1% for local recurrence and 24.0% for distant metastases. In the multivariate analysis, survival decreased with age and increased over time but significantly only over the last study period. Surgical resection and palliative chemotherapy were other determinants of prognosis for distant metastases whereas surgical resection and palliative radiotherapy did influence the prognosis for local recurrence. CONCLUSION: Substantial advances in the management of recurrences have been achieved over time. More effective treatments and mass screening represent promising approaches to decrease this problem.

Dietary patterns and the risk of colorectal adenoma recurrence in a European intervention trial.

The relations between individual foods and nutrients to colorectal tumours are conflicting. Few studies have taken into account the interdependence between individual components of diet and their possible interactions. The aim of the study was to examine the associations between dietary patterns and the risk of colorectal adenoma recurrence in the European fibre-calcium intervention trial. Among the 640 patients with confirmed adenomas at the index colonoscopy, 592 had an initial dietary assessment using a diet history questionnaire. The present analysis was restricted to 277 men and 165 women without history of adenoma prior to the index colonoscopy and who completed the study. The main end point was the 3-year recurrence of adenomas. Principal component analysis was used to identify dietary patterns from 50 food groups. Ninety-two patients presented new colorectal adenomas at the 3-year colonoscopy (65 men and 27 women). In men, three meaningful dietary patterns emerged from analysis, explaining 21.3% of variability. They were called 'Mediterranean', 'Sweets and snacks' and 'High fat and proteins' patterns. None of them were significantly related to the overall recurrence of colorectal adenomas either in univariate or multivariate analyses. Among women, the 'Mediterranean', the 'Western' and the 'Snacks' patterns explained 21.9% of variability. The 'Mediterranean' pattern characterized by a high consumption of olive oil, vegetables, fruit, fish and lean meat significantly reduced adenoma recurrence [second tertile: adjusted odds ratio (OR)=0.50, 95% confidence interval (CI)=0.18-1.42; third tertile: adjusted OR=0.30, 95% CI=0.09-0.98; P for linear trend=0.04]. The 'Western' and 'Snacks' patterns were not associated with recurrence among women. In conclusion, this study suggests that the Mediterranean dietary pattern may reduce the recurrence of colorectal adenomas, at least in women. These exploratory results need to be confirmed by larger studies.

Colorectal adenoma characteristics as predictors of recurrence.

PURPOSE: The identification of groups with a high risk of colorectal adenoma recurrence remains a controversial issue for clinicians. This study was designed to assess the predictive value of initial patient and adenoma characteristics of the three-year recurrence. METHODS: The study population was composed of 552 patients with resected colorectal adenomas who completed the European Fiber-Calcium Intervention trial. At both baseline and three-year examinations, the characteristics of adenomas were recorded according to a standardized protocol. The main outcomes measured were the three-year overall recurrence, recurrence of multiple adenomas, recurrence of advanced adenomas (size > or = 1 cm or tubulovillous/villous architecture or moderate/severe dysplasia), and proximal and distal recurrence. RESULTS: A three-year recurrence was observed in 122 patients (22.1 percent), and more than one-half of them had recurrent adenomas on the proximal colon. After adjustment for patient characteristics and treatment allocation, the number of adenomas and their proximal location at baseline were the main predictors of recurrence. In comparison with patients who had one or two adenomas on the distal colon, patients with three or more adenomas with at least one of them located on the proximal colon had a much higher risk of overall recurrence (5.3; 95 percent confidence interval, 2.7-10.3), proximal recurrence (8.5; 95 percent confidence interval, 4.1-18), and advanced adenoma recurrence (5.5; 95 percent confidence interval, 2.4-12.6). CONCLUSIONS: Follow-up colonoscopies in patients with adenomas should include careful examination of the proximal colon. The time interval between follow-up examinations could probably be extended beyond three years in patients who have only one or two distal adenomas.

Sporadic colorectal cancers with defective mismatch repair display a number of specific morphological characteristics: relationship between the expression of hMLH1 and hMSH2 proteins and clinicopathological features of 273 adenocarcinomas.

AIMS: The aim of this study was to assess the independent value of pathological criteria in the diagnosis of mismatch repair (MMR)-defective sporadic colorectal cancers. METHODS AND RESULTS: Resected colorectal adenocarcinomas (n = 273) were reviewed in order to identify a number of specific morphological features of MMR-defective carcinomas. Of the 273 cases, 35.2% were right-sided and 5.9% were poorly differentiated. Focal extracellular mucin secretion was seen in 5.1% of cases and a stromal follicular reaction in 4.6%. The expression of the two major MMR proteins hMLH1 and hMSH2 was studied by immunohistochemistry. Carcinomas were considered deficient in the MMR system when a loss of nuclear signal in neoplastic cells was observed for one of the proteins. Such an extinction was seen in 37 of the cases (13.6%). The hMLH1 protein was the one most frequently altered (86.5%). After multivariate analysis, three independent factors were significantly associated with MMR deficiency: proximal location [odds ratio (OR) = 9.30; 95% confidence interval (CI) 2.79, 30.98], the presence of a true stromal follicular reaction (OR = 13.60; 95% CI 2.98, 62.00) and poor differentiation (OR = 8.33; 95% CI 1.63, 40.32). CONCLUSIONS: These results confirm that sporadic colorectal MMR-defective adenocarcinomas display certain specific morphological characteristics. However, these pathological features are not sufficiently predictive and immunohistochemistry is needed to identify such tumours accurately.

A simulation model for evaluating the medical and economic outcomes of screening strategies for colorectal cancer.

Mathematical models have been shown to be useful in predicting the cost-effectiveness of cancer screening programmes. We designed a computer macro-simulation model aimed at predicting the cost-effectiveness of alternative colorectal cancer screening strategies. This model was built to determine the cost-effectiveness of a biennial screening programme using the Hemoccult test in Burgundy (France). It was validated with data from the Danish randomized study. Estimates of our model showed an extremely close concordance with observed results in the Danish study. The observed mortality reduction was 18.0% and the estimated mortality reduction was 18.4%. Preliminary data from the Burgundy study predict a 14.6% colorectal cancer mortality reduction after 10 years. Sensitivity analyses were performed with different assumptions regarding the participation rates and the lead-time. This model can serve to assess the cost-effectiveness of a variety of screening modalities.

Microsatellite instability and intratumoural heterogeneity in 100 right-sided sporadic colon carcinomas.

Microsatellite instability has been proposed as an alternative pathway of colorectal carcinogenesis. The aim of this study was to evaluate the interest of immunohistochemistry as a new tool for highlighting mismatch repair deficiency and to compare the results with a PCR-based microsatellite assay. A total of 100 sporadic proximal colon adenocarcinomas were analysed. The expression of hMLH1, hMSH2 and hMSH6 proteins evaluated by immunohistochemistry was altered in 39% of the cancers, whereas microsatellite instability assessed by PCR was detected in 43%. There was discordance between the two methods in eight cases. After further analyses performed on other tumoural areas for these eight cases, total concordance between the two techniques was observed (Kappa=100%). Our results demonstrate that immunohistochemistry may be as efficient as microsatellite amplification in the detection of unstable phenotype provided that at least two samples of each carcinoma are screened, because of intratumoural heterogeneity.

Trends in gastric cancer incidence in a well-defined French population by time period and birth cohort.

Epidemiological studies have shown a marked decline in gastric cancer incidence and opposite patterns between proximal and distal sites among different populations. Little is known about trends by histological type. The aim of this study was to analyse the change in gastric cancer incidence patterns by investigating the role of temporal components as determinants of such trends in the population of the Côte d'Or area (France) registered between 1976 and 1995. Gastric cancer incidence decreased over time. There was a decrease in incidence rates for distal cancers (-3.5% P < 0.001 per year in men and -4.6% P < 0.01 in women). In contrast, there was a non-significant increase of proximal cancer incidence in men and in women. Rates of adenocarcinomas decreased, whereas the incidence rates of undifferentiated carcinomas and of other histological types remained quite stable. There was a decrease in cumulative risk throughout the studied cohorts, whereas risk for proximal cancer remained stable and decreased slightly for distal localization. For adenocarcinomas, earlier birth cohorts showed a slight decrease in rates, whereas there was an increase for recent cohorts. Subsite and histological-specific analysis, in revealing different time trends in incidence, suggest, at least partly, different aetiologies for gastric cancer, and future aetiological studies must distinguish proximal and distal cancers.