Showing papers by "Dale C. Snover published in 2000"

The effect of fecal occult-blood screening on the incidence of colorectal cancer.

Abstract: Background Both annual testing for fecal occult blood and biennial testing significantly reduce mortality from colorectal cancer. However, the effect of screening on the incidence of colorectal cancer remains uncertain, despite the diagnosis and removal of precancerous lesions in many persons who undergo screening. Methods We have followed the participants in the Minnesota Colon Cancer Control Study for 18 years. A total of 46,551 people, most of whom were 50 to 80 years old, were enrolled between 1975 and 1978 and randomly assigned to annual screening, biennial screening, or usual care (the control group). Those assigned to the screening groups were asked to prepare and submit two samples from each of three consecutive stools for guaiac-based testing. Those with at least one positive slide in the set of six were offered a diagnostic examination that included colonoscopy. Screening was conducted between 1976 and 1982 and again between 1986 and 1992. Study participants have been followed with respect to ne...

Hepatitis C, iron, and hemochromatosis gene mutations. A meaningful relationship or simple cohabitation?

Abstract: Since the discovery of hepatitis C and the subsequent use of interferon as treatment for chronic infections, hepatologists have been searching for criteria that might predict which patients are likely to benefit from therapy. For patients with an inadequate or no response to therapy, methods to improve or augment therapy have been sought. Factors generally considered predictive of a poor response to therapy include infection with genotype 1 virus, long duration of infection, high viral load, and fibrosis revealed on biopsy.1,2 Most of these factors are not used generally to make decisions about treatment, however.2 Hepatologists have been particularly ambiguous in their use of histologic features. Several studies indicate that fibrosis and piecemeal necrosis (interface hepatitis) are predictors of poor response to therapy, yet these same factors (particularly fibrosis) are used as arguments in favor of initiating interferon therapy (since fibrosis indicates that the patient is being harmed by the virus).2 Another factor proposed by some as important in determining response to therapy and also as providing a potential way to improve therapy is iron accumulation in the liver. The article in the current issue of the Journal by Pirisi et al3 adds to a number of reports published during the last several years dealing with the issue of hepatitis C, iron deposition, and mutations of the hemochromatosis (HFE) gene.3 The published works in this area vary markedly in the number of patients studied and the methods used, particularly differences in how iron content is assessed, making it difficult to compare the studies and to derive firm conclusions. The article by Pirisi et al3 describes a moderately sized study that investigated both iron deposition and mutations in the HFE gene in a reasonably rigorous fashion. In particular, it reviewed the liver biopsy with an eye toward the pattern of deposition of iron within different cellular compartments of the liver rather than simply reporting overall iron levels, something that many articles on the subject do not do. It also directly addresses the issue of the relationship of mutations in the HFE gene with stage and grade of disease, as well as with iron accumulation, with some information provided on response to therapy. So what are the relevant issues, and what were the findings of this study and others? The main issues involve the following: (1) whether iron deposition itself predicts response to therapy for hepatitis C, (2) whether this effect, if any, is the result of the iron or if the iron accumulation is the result of other factors (in particular fibrosis) that are more important predictive factors, and (3) whether removal of the iron improves the outcome of therapy. For the first question, there is consensus (with a few exceptions4) that increased liver iron deposition, particularly as measured by histologic assessment, is correlated with a poor response to interferon therapy.5-11 Most articles that provide data also report that iron accumulation is associated increased fibrosis.5-7,12-15 The article by Pirisi et al3 confirms these findings. The finding of excess iron in association with increased fibrosis suggests that iron might act as a cofactor increasing liver damage or, alternatively, that livers with preexisting fibrosis tend to accumulate iron or possibly that these are unrelated coincidental findings related to a third factor, such as duration of disease or age. Unfortunately, none of the articles in the literature address this topic directly. Perhaps the only way to address it would be with a series of sequential biopsies in individual patients to determine whether the iron deposition or the fibrosis comes first. Such a study may well never be done, and in many ways, the question is somewhat semantic from prognostic and therapeutic viewpoints. It is interesting that hepatitis C is not unique in