The overdiagnosis nightmare: a time for caution

Overdiagnosis (and overtreatment) of cancers not bound to become symptomatic during lifetime is an unavoidable drawback of mammography screening. The magnitude of overdiagnosis has been estimated to be in the range of 5-10%, and thus acceptable in view of screening benefits as to reduced mortality. In a recent research article in BMC Women's Health, Jørgensen, Zahl and Gøtzsche suggest that overdiagnosis may be as high as 33%, based on their analysis of breast cancer incidence in screened and non-screened areas in Denmark. Here we consider how reliable such analyses can be, why it might have been useful to adjust comparisons between screened and non-screened areas for early detection lead time, and what further evidence might be needed to build on or confirm these results

Fasting blood glucose, glycaemic control and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer

BACKGROUND: Diabetic men have lowered overall risk of prostate cancer (PCa), but the role of hyperglycaemia is unclear. In this cohort study, we estimated PCa risk among men with diabetic fasting blood glucose level. METHODS: Participants of the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC) were linked to laboratory database for information on glucose measurements since 1978. The data were available for 17,860 men. Based on the average yearly level, the men were categorised as normoglycaemic, prediabetic, or diabetic. Median follow-up was 14.7 years. Multivariable-adjusted Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for prostate cancer overall and separately by Gleason grade and metastatic stage. RESULTS: In total 1,663 PCa cases were diagnosed. Compared to normoglycaemic men, those men with diabetic blood glucose level had increased risk of PCa (HR 1.52; 95% CI 1.31-1.75). The risk increase was observed for all tumour grades, and persisted for a decade afterwards. Antidiabetic drug use removed the risk association. Limitations include absence of information on lifestyle factors and limited information on BMI. CONCLUSIONS: Untreated diabetic fasting blood glucose level may be a prostate cancer risk factor.Peer reviewe

Overdiagnosis and overtreatment of early detected prostate cancer

Early detection of prostate cancer is associated with the diagnosis of a considerable proportion of cancers that are indolent, and that will hardly ever become symptomatic during lifetime. Such overdiagnosis should be avoided in all forms of screening because of potential adverse psychological and somatic side effects. The main threat of overdiagnosis is overtreatment of indolent disease. Men with prostate cancer that is likely to be indolent may be offered active surveillance. Evaluation of active surveillance studies and validation of new biological parameters for risk assessment are expected

Lung cancer risk among German male uranium miners: a cohort study, 1946–1998

From 1946 to 1990 extensive uranium mining was conducted in the southern parts of the former German Democratic Republic. The overall workforce included several 100 000 individuals. A cohort of 59 001 former male employees of the Wismut Company was established, forming a large retrospective uranium miners' cohort for the time period 1946–1998. Mean duration of follow-up was 30.5 years with a total of 1 801 630 person-years. Loss to follow-up was low at 5.3%. Of the workers, 16 598 (28.1%) died during the study period. Based on 2388 lung cancer deaths, the radon-related lung cancer risk is evaluated. The excess relative risk (ERR) per working level month (WLM) was estimated as 0.21% (95% CI: 0.18–0.24). It was dependent on time since exposure and on attained age. The highest ERR/WLM was observed 15–24 years after exposure and in the youngest age group (<55 years of age). While a strong inverse exposure-rate effect was detected for high exposures, no significant association was detected at exposures below 100 WLM. Excess relative risk /WLM was not modified by duration of exposure. The results would indicate the need to re-estimate the effects of risk modifying factors in current risk models as duration of exposure did not modify the ERR/WLM and there was only a modest decline of ERR/WLM with increasing time since exposure

Effects of Aging on Endotoxin Tolerance Induced by Lipopolysaccharides Derived from Porphyromonas gingivalis and Escherichia coli

Background: Periodontitis is a bacterially induced chronic inflammatory disease. Exposure of the host to periodontal pathogens and their virulence factors induces a state of hyporesponsiveness to subsequent stimulations, termed endotoxin tolerance. Aging has a profound effect on immune response to bacteria challenge. The aim of this study was to explore the effects of aging on endotoxin tolerance induced by Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS) and Escherichia coli (E. coli) LPS in murine peritoneal macrophages. Methodology/Principal Findings: We studied the cytokine production (TNF-aand IL-10) and Toll-like receptor 2, 4 (TLR2, 4) gene and protein expressions in peritoneal macrophages from young (2-month-old) and middle-aged (12-month-old) ICR mice following single or repeated P. gingivalis LPS or E. coli LPS stimulation. Pretreatment of peritoneal macrophages with P. gingivalis LPS or E. coli LPS resulted in a reduction in TNF-a production and an increase in IL-10 production upon secondary stimulation (p,0.05), and the markedly lower levels of TNF-a and higher levels of IL-10 were observed in macrophages from young mice compared with those from middle-aged mice (p,0.05). In addition, LPS restimulations also led to the significantly lower expression levels of TLR2, 4 mRNA and protein in macrophages from young mice (p,0.05). Conclusions/Significance: Repeated LPS stimulations triggered endotoxin tolerance in peritoneal macrophages and the ability to develop tolerance in young mice was more excellent. The impaired ability to develop endotoxin tolerance resulte

Stellar Structure and Evolution: Deductions from Hipparcos

During the last decade, the understanding of fine features of the structure and evolution of stars has become possible as a result of enormous progress made in the acquisition of high-quality observational and experimental data and of new developments and refinements in the theoretical description of stellar plasmas. The confrontation of high-quality observations with sophisticated stellar models has allowed many aspects of the theory to be validated, and several characteristics of stars relevant to Galactic evolution and cosmology to be inferred. This paper is a review of the results of recent studies undertaken in the context of the Hipparcos mission, taking benefit of the high-quality astrometric data it has provided. Successes are discussed, as well as the problems that have arisen and suggestions proposed to solve them. Future observational and theoretical developments expected and required in the field are also presented.Comment: 56 pages, including 9 figures, Ann. Rev. Astron. Astrophys. Vol. 38, September 2000 (in press