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Costs and Benefits of Performing Health Service EvaluationsWell-designed evaluations of health services are frequently performed; however, the extent to which the benefits of these evaluations justify their costs is not well documented. Soderstrom et al. (p. 1118) calculated the benefits and costs of one such evaluation, the Quebec Neuroblastoma Screening Project (QNSP), which screened Quebec newborns between 1989 and 1994 for neuroblastoma. This screening did not reduce neuroblastoma mortality and caused adverse health effects. Had the QNSP not been undertaken, Soderstrom et al. argue that screening would have been used across North America between 1989 and 2002. By preventing this, the authors calculate, the QNSP averted for the United States and Canada $574.1 million in health costs, unnecessary treatment for 9223 children, and false-positive findings for 5003 children screened. The authors conclude that the benefits of the QNSP evaluation clearly justify its costs, $8.7 million. They argue that the result raises an important policy issue: are well-designed evaluations now being under- or over-used?
In a related editorial (p. 1105), Levy emphasizes the importance of health care assessment in public policy and encourages citizens not only to advocate for health care assessment and other research funding but also to participate in the research itself.
Vimentin Methylation and Colon Cancer
In cancer cells, the transcription of tumor suppressor genes is often silenced by increased or aberrant DNA methylation, and aberrantly methylated DNA has been proposed as a potential tumor marker. Chen et al. (p. 1124) used methylationspecific polymerase chain reaction to determine the methylation status of exon-1 of the vimentin gene, which is nonetheless already silent in the colon, in DNA from colon cancer cell lines, normal tissues of healthy subjects, and tumors of colon cancer patients and in fecal DNA from colon cancer patients and healthy subjects. Aberrant vimentin methylation was detected in 83% and 53% of tumors from two independent groups of colon cancer patients, respectively, and in 46% of fecal DNA from a third set of colon cancer patients, with 43% sensitivity for detecting stage I and II cancers. The specificity of the test with fecal DNA was 90%. The authors conclude that aberrant methylation of exon-1 of the vimentin gene is a novel biomarker of colon cancer that can be detected in fecal DNA from nearly half of colon cancer patients.
In a related editorial, Brenner and Rennert (p. 1107) emphasize the need to create more sensitive, non-invasive colorectal cancer screening methods that are cost-effective and can detect adenomas. They also discuss potential technical problems of fecal based DNA testing.
Effects of Various Definitions for Abnormal PSA Levels
Welch et al. (p. 1132) used data from the 2001–2002 National Health and Nutrition Examination Survey to examine the effect of lowering the threshold defining an abnormal prostate-specific antigen (PSA) test on the number of American men who would be labeled abnormal by a single PSA test. They estimated that approximately 1.5 million American men aged 40 to 69 years have a PSA level greater than 4.0 ng/mL. With a threshold of 2.5 ng/mL, an additional 1.8 million men would be labeled abnormal, if all men were screened. Roughly 10 times more men have a PSA level over 4.0 ng/mL than are expected to die from prostate cancer in the next 10 years. The authors conclude that, until there is evidence that screening is effective, lowering the PSA threshold to 2.5 ng/mL would be a mistake.
AJCC Tumor Stage After Neoadjuvant Chemotherapy
The extent of residual tumor after neoadjuvant chemotherapy is used as an intermediate endpoint for breast cancer relapse and survival. Carey et al. (p. 1137) assessed the pathologic stage of residual tumors in 132 patients with nonmetastatic breast cancer after they had undergone neoadjuvant chemotherapy and examined the ability of the revised 2003 American Joint Committee on Cancer (AJCC) tumor–node–metastasis (TNM) staging system, which considers both the number of involved axillary lymph nodes and the extent of tumor in the breast, to predict survival. They found that pathologic stage of residual tumor was strongly associated with both distant disease-free survival and overall survival. They conclude that classification of residual tumor in the breast and axillary surgical specimens after neoadjuvant chemotherapy using the revised AJCC TNM system is useful for predicting distant relapse and survival.
Plasmacytoid Predendritic Cells and Imiquimod Treatment
Imiquimod, a topical treatment for several skin cancer types, induces proinflammatory cytokine production that stimulates an antitumor immune response. Urosevic et al. (p. 1143) characterized imiquimod-induced immune activation in superficial basal cell carcinomas, cutaneous T-cell lymphomas, and Bowen disease. They found that, after imiquimod treatment of these skin tumors, expression of various interferon 
(IFN-á)-inducible genes increased, plasmacytoid predendritic cells (PDCs) were recruited and activated in all lesion types, and activated PDCs produced IFN-á. They also found that in all tumor types imiquimod induced similar gene expression patterns that were associated with the number of PDCs recruited to the treatment site and that the strength of the imiquimod-induced immune response was directly associated with the number of PDCs recruited to the tumor. They concluded that PDCs appear to have a role in the responsiveness of skin tumors to imiquimod treatment.
Body Size and Composition and Myeloid Leukemia Risk
To determine if body size and composition are associated with risk of lymphohematopoietic malignancies, MacInnis et al. (p. 1154) followed 40,909 people aged 27 to 75 years for an average of 8.4 years. The authors measured waist and hip circumference, height, and weight, calculated the waist-to-hip ratio and the body mass index, and used bioelectrical impedance analysis to measure fat mass and fat-free mass of each participant. They gathered information about malignancies from the population cancer registry. The authors found that risk of myeloid leukemia was positively associated with body mass index, fat-free mass, and waist circumference, whereas risks of multiple myeloma, lymphocytic leukemia, hairy cell leukemia, Hodgkin lymphoma, and non-Hodgkin lymphoma were not associated with body size or composition.
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