© 1999 by Oxford University Press
Journal of the National Cancer Institute, Vol. 91, No. 22, 1905,
November 17, 1999
© 1999 Oxford University Press
IN THIS ISSUE |
By collecting data on 101,604 prostatectomies from Medicare claims filed from 1991 through 1994, Yao and Lu-Yao (p. 1950) investigated relationships between the volume of prostatectomies handled by a hospital, the length of a patient's stay in the hospital, and patient outcomes. Comparisons across hospitals revealed that rates of readmission, serious complications, and mortality within 30 days of surgery were inversely proportional to prostatectomy volumes. The average stay in a low-volume hospital was 8.51 days versus 7.81 days in a high-volume hospital. Hospitals that increased their relative prostatectomy volume over time showed a 57% greater reduction in the mean length of a patient's stay compared with hospitals that decreased their relative prostatectomy volume. However, changes in prostatectomy volume did not affect the frequency of serious complications, mortality, and readmission. The authors conclude that an increase in a hospital's prostatectomy volume may decrease the length of a patient's hospital stay without an adverse impact on patient outcomes.
In an editorial, Potosky and Warren (p. 1906) explore whether the patient outcomes assessed by Yao and Lu-Yao in this study are useful indicators of the quality of care. The editorialists note that the study did not assess surgeon volume or referral patterns, which may be as important as hospital volume. Furthermore, the editorial writers observe that the magnitude of the differences in outcomes by volume was small and may have limited clinical meaning. They emphasize that, until more research is available on the long-term outcomes of prostatectomy compared with other treatment strategies such as radiation therapy or conservative management, the best indicator of quality of care may be the extent to which men are fully informed of their treatment options and associated long-term outcomes.
Colon Cancer: Blacks and Whites
African-Americans generally experience lower survival from colon cancer than Caucasian Americans. This disparity has been attributed to many sources, including diagnosis at later disease stage, inadequate treatment, and socioeconomic factors. Dignam et al. (p. 1933) studied survival and related end points among African-American and Caucasian patients with colon cancer who were enrolled in five different randomized clinical trials of adjuvant therapy conducted by the National Surgical Adjuvant Breast and Bowel Project. According to the authors, the randomized clinical trial setting provides uniformity in controlling for disease stage and treatment plan between blacks and whites. They observed that the black patients had a statistically significantly greater risk of death than the white patients but not of colon cancer recurrence. Treatment efficacy appeared similar between the two groups. The authors conclude that earlier detection and adjuvant therapy could appreciably improve colon cancer prognosis for African-Americans, and they recommend more investigations to understand the differences in outcomes between blacks and whites.
In an editorial, Brawley and Freeman (p. 1908) point out that, in randomized trials with adequate statistical power and properly controlled confounding variables, equal treatments yield equal outcomes regardless of race. They advise minority health researchers and advocates to define additional pressing questions that ultimately can eliminate race-related disparities and focus on issues such as access to and utilization of quality cancer care.
Cancer Cell Radiation Sensitivity
Activation of transcription factor NF-
B occurs shortly after tissue is exposed to ionizing
radiation, leading to expression of genes involved in the inflammatory response induced by
irradiation. Whether activation of NF-B protects cells from radiation-induced cell death is
less clear. Pajonk et al. (p. 1956), by engineering two types of malignant cells
(PC3 prostate and HD-MyZ Hodgkin's) to produce a variant form of IB
(an
inhibitor of NF-B) that cannot be phosphorylated, investigated the possibility that
NF-B modifies the radiosensitivity of cancer cells. This variant form of IB binds
to NF-B and is not released. Thus, NF-B cannot be activated in response to ionizing
radiation. The investigators found that inhibition of NF-B in this manner did not reduce cell
survival following irradiation. Their data did indicate, however, that the ability to activate
NF-B in these two types of cancer cells is important for their general survival.
In an accompanying editorial, Dritschilo (p. 1910) concludes that the
findings of Pajonk et al. should be interpreted with caution. He states that the data show that
mutant IB expression in both PC3 prostate cells and HD-MyZ Hodgkin's cells
results in apoptotic cell death but do not provide insight into the role of NF-B regulation in
intrinsic radiation sensitivity.
Glutathione S-Transferase and Breast Cancer
Glutathione S-transferases M1 (GST-M1) and T1 (GST-T1) are enzymes that participate in the metabolism (mainly inactivation, but activation is possible) of a wide range of chemical carcinogens. Deletion of the encoding genes (GSTM1 and GSTT1) results in a loss of corresponding enzyme activity and has been associated with cancer susceptibility. García-Closas et al. (p. 1960) have investigated 466 case patients with breast cancer and 466 matched control subjects to determine whether deletion of the GSTM1 and/or GSTT1 genes increases the risk of developing breast cancer. They report that deletion of these genes, either individually or together, is not associated with a substantially increased risk of this disease.
Heat Shock Protein Inhibitor
Heat shock protein 90 (Hsp90) is a molecular chaperone; i.e., it helps other proteins avoid misfolding pathways that produce inactive or aggregated states. Geldanamycin and herbimycin are benzoquinone ansamycin antibiotics that inhibit the function of Hsp90 and have been shown to possess anticancer activity. Interaction of these compounds with Hsp90 leads to cellular depletion of several important oncogenic proteins, such as Raf-1 and mutant (but not wild-type) p53. 17-Allylamino,17-demethoxygeldanamycin (17AAG) is a synthetic analogue of geldanamycin that is currently being evaluated in phase I clinical trials. Kelland et al. (p. 1940) have investigated whether expression of the NQO1 gene, which encodes the enzyme DT-diaphorase, affects the anticancer activity of 17AAG. DT-diaphorase has been shown to activate other quinone-containing anticancer drugs. The investigators found a positive relationship between DT-diaphorase expression level and inhibition of tumor cell proliferation in vitro and in vivo by 17AAG.
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||