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. © 2001 Cancer Research Campaign http://www.bjcancer.co

Cystinosin, MPDU1, SWEETs and KDELR Belong to a Well-Defined Protein Family with Putative Function of Cargo Receptors Involved in Vesicle Trafficking

Classification of proteins into families based on remote homology often helps prediction of their biological function. Here we describe prediction of protein cargo receptors involved in vesicle formation and protein trafficking. Hidden Markov model profile-to-profile searches in protein databases using endoplasmic reticulum lumen protein retaining receptors (KDEL, Erd2) as query reveal a large and diverse family of proteins with seven transmembrane helices and common topology and, most likely, similar function. Their coding genes exist in all eukaryota and in several prokaryota. Some are responsible for metabolic diseases (cystinosis, congenital disorder of glycosylation), others are candidate genes for genetic disorders (cleft lip and palate, certain forms of cancer) or solute uptake and efflux (SWEETs) and many have not yet been assigned a function. Comparison with the properties of KDEL receptors suggests that the family members could be involved in protein trafficking and serve as cargo receptors. This prediction sheds new light on a range of biologically, medically and agronomically important proteins and could open the way to discovering the function of many genes not yet annotated. Experimental testing is suggested

Screening for colorectal cancer: random comparison of guaiac and immunochemical faecal occult blood testing at different cut-off levels

Immunochemical faecal occult blood testing (FIT) provides quantitative test results, which allows optimisation of the cut-off value for follow-up colonoscopy. We conducted a randomised population-based trial to determine test characteristics of FIT (OC-Sensor micro, Eiken, Japan) screening at different cut-off levels and compare these with guaiac-based faecal occult blood test (gFOBT) screening in an average risk population. A representative sample of the Dutch population (n=10 011), aged 50–74 years, was 1 : 1 randomised before invitation to gFOBT and FIT screening. Colonoscopy was offered to screenees with a positive gFOBT or FIT (cut-off 50 ng haemoglobin/ml). When varying the cut-off level between 50 and 200 ng ml−1, the positivity rate of FIT ranged between 8.1% (95% CI: 7.2–9.1%) and 3.5% (95% CI: 2.9–4.2%), the detection rate of advanced neoplasia ranged between 3.2% (95% CI: 2.6–3.9%) and 2.1% (95% CI: 1.6–2.6%), and the specificity ranged between 95.5% (95% CI: 94.5–96.3%) and 98.8% (95% CI: 98.4–99.0%). At a cut-off value of 75 ng ml−1, the detection rate was two times higher than with gFOBT screening (gFOBT: 1.2%; FIT: 2.5%; P<0.001), whereas the number needed to scope (NNscope) to find one screenee with advanced neoplasia was similar (2.2 vs 1.9; P=0.69). Immunochemical faecal occult blood testing is considerably more effective than gFOBT screening within the range of tested cut-off values. From our experience, a cut-off value of 75 ng ml−1 provided an adequate positivity rate and an acceptable trade-off between detection rate and NNscope

Screening of colorectal cancer State of the art and implementation in France

Le cancer colorectal représente un problème majeur de santé publique dans les pays industrialisés. Il remplit les caractéristiques d’une maladie justifiant un dépistage de masse. Dans ce contexte, des recherches importantes ont été réalisées au cours des 15 dernières années pour évaluer la possibilité de diminuer l’incidence ou la mortalité due au cancer colorectal. Les données des études cas-témoin et des études randomisées indiquent que la réalisation d’un test de recherche d’un saignement occulte dans les selles permet de diminuer la mortalité par cancer colorectal. Toutes les études ont évalué un test au guaiac (Hemoccult®) chez des sujets de 50 à 74 ans, avec une coloscopie en cas de positivité du test. Pour obtenir une diminution significative de mortalité, la participation initiale doit se situer entre 50 et 65% et rester élevée dans les campagnes ultérieures. Le temps est venu d’organiser au niveau des pays, le dépistage du cancer colorectal, malgré les limites des tests actuels de recherche d’un saignement occulte dans les selles. Des recherches sont en cours pour améliorer les performances de ces tests

Screening for colorectal cancer with occult blood test in the average risk population

Dans l'état actuel de nos connaissances, seule une stratégie de dépistage du cancer colorectal, alors qu'il est encore asymptomatique, peut faire évoluer à court terme le grave problème que pose ce cancer. Les études cas-témoin et les études randomisées indiquent qu'il est possible de diminuer la mortalité par cancer colorectal par la recherche d'un saignement occulte dans les selles. Toutes les études ont évalué le test Hémoccult, fait tous les 2 ans entre 50 et 74 ans, suivi d'une coloscopie en cas de test positif. Pour obtenir une diminution de mortalité, la participation doit se situer entre 50 et 60 % à la première campagne et rester élevée lors des campagnes ultérieures. La diminution de la mortalité dans les programmes organisés et évalués se situe entre 15 et 20 %. Malgré la limitation des tests actuels, il est temps que le dépistage du cancer colorectal devienne une réalité

Colon cancer in France: Evidence for improvement in management and survival

Background: Cancer registries recording all cases diagnosed in a well defined population represent the only way to assess real changes in the management of colon cancer at the population level. Aims: To determine trends over a 23 year period in treatment, stage at diagnosis, and prognosis of colon cancer in the Côte-d'Or region, France. Patients: A total of 3389 patients with colon cancer diagnosed between 1976 and 1998. Methods: Time trends in clinical presentation, surgical treatment, chemotherapy treatment, stage at diagnosis, postoperative mortality, and survival were studied. A non-conditional logistic regression was performed to obtain an odds ratio for each period adjusted for the other variables. To estimate the independent effect of the period on prognosis, a relative survival analysis was performed. Results: Between 1976 and 1991, the resection rate increased from 69.3% to 91.9% and then remained stable. This increase was particularly marked in the older age group (56.4% to 90.5%). The proportion of stage III patients treated with adjuvant chemotherapy rose from 4.1% for the 1989–1990 period to 45.7% for the 1997–1998 period. Over the 23 years of the study the proportion of stage I and II patients increased from 39.6% to 56.6%, associated with a corresponding decrease in the proportion of patients with advanced stages. Postoperative mortality decreased from 19.5% to 7.3%. This led to an improvement in five year relative survival (from 33.0% for the 1976–1979 period to 55.3% for the 1992–1995 period). Conclusions: Advances in the management of colon cancer have resulted in improving the prognosis of this disease. However, progress is still possible, particularly in the older age group