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

Characterization of Cellular Responses Involved in Reparative Dentinogenesis in Rat Molars

During primary dentin formation, differentiating primary odontoblasts secrete an organic matrix, consisting principally of type I collagen and non-collagenous proteins, that is capable of mineralizing at its distal front. In contrast to ameloblasts that form enamel and undergo programed cell death, primary odontoblasts remain metabolically active in a functional tooth. When dentin is exposed to caries or by operative procedures, and when exposed dentinal tubules are treated with therapeutic dental materials, the original population of odontoblasts is often injured and destroyed. The characteristics of the replacement pool of cells that form reparative dentin and the biologic mechanisms that modulate the formation of this matrix are poorly understood. Based on the hypothesis that events governing primary dentinogenesis are reiterated during dentin repair, the present study was designed to test whether cells that form reparative dentin are odontoblast-like. Cervical cavities were prepared in rat first molars to generate reparative dentin, and animals were killed at various time intervals. In situ hybridization with gene-specific riboprobes for collagen types I and III was used to study de novo synthesis by cells at the injured dentin-pulp interface. Polyclonal antibodies raised against dentin sialoprotein (DSP), a dentin-specific protein that marks the odontoblast phenotype, were used in immunohistochemical experiments. Data from our temporal and spatial analyses indicated that cells forming reparative dentin synthesize type I but not type III collagen and are immunopositive for DSP. Our results suggest that cells that form reparative dentin are odontoblast-like.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67273/2/10.1177_00220345950740021301.pd

NEURAL-NETWORK PROCESSING OF CERVICAL SMEARS CAN LEAD TO A DECREASE IN DIAGNOSTIC VARIABILITY AND AN INCREASE IN SCREENING EFFICACY - A STUDY OF 63 FALSE-NEGATIVE SMEARS

A realistic approach for decreasing the number of erroneous diagnoses plaguing cervical cytology screening is to try to reduce the amount of nondiagnostic visual information. The neural network of PAPNET selects 128 cytological views from the routinely prepared smear which in digitized form can be displayed on a high-resolution videoscreen. From these 128 videotiles the abnormal ones can be selected by the diagnostician and brought together on the ''summarizing videoscreen'' containing 16 tiles. Thus, the diagnostic information can be further condensed. This facilitates the proper interpretation of the diagnostic cell material dispersed over the smear. A series of 63 false-negative smears were rescreened twice conventionally and twice using the PAPNET-assisted method. We found that, using PAPNET, the screening efficacy increased and the diagnostic variability decreased. The PAPNET in particular proved to be superior for smears containing few abnormal cells and cases of malignancies of the reserve cell lineage

Does plasminogen activator inhibitor-1 (PAI-1) control trophoblast invasion? A study of fetal and maternal tissue in intrauterine, tubal and molar pregnancies.

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