Survival of colorectal cancer patients in relation to duration of symptoms and other prognostic factors

The effect of duration of symptoms and other prognostic factors on survival was studied by interview using a population-based sample of 154 colorectal cancer patients. The authors found that symptom durations of up to approximately one year before diagnosis had no effect on survival. In addition, it was found that the total number of symptoms was a statistically significant predictor of survival, although no single symptom had a significant effect. Stage, sex, and site also were found to be significant predictors of survival, whereas age, socioeconomic status, and other factors were not predictive. Research supported by NCI grant 2R18CA-16404. Work performed at the Fred Hutchinson Cancer Research Center.     

Fibrosing alveolitis: CT-pathologic correlation

Computed tomography (CT) was performed within 10 days of open lung biopsy in nine patients with fibrosing alveolitis. One-centimeter collimation contiguous scans through the chest were obtained in all patients. Additional 1.5-mm collimation scans were obtained in the area in which lung biopsy was later performed in six patients. In seven patients, CT demonstrated patchy involvement of the lung parenchyma, areas with a reticular pattern being intermingled with areas of normal lung. The reticular pattern was associated with cystic spaces 2-4 mm in diameter and was more severe in the lung periphery. Histologically, the reticular pattern corresponded to areas of irregular fibrosis. One patient had diffuse honeycombing (2-20-mm cysts), and one had honeycombing only in the lung periphery. In all patients, CT clearly defined the architectural changes seen on open lung biopsy. These changes were much better seen on the 1.5-mm than on the 10-mm collimation scans. CT may be helpful in determining the pattern and distribution of lung involvement in patients with fibrosing alveolitis and in guiding the surgeon to the most appropriate area(s) for biopsy.     

Pulmonary lymphangiomyomatosis: correlation of CT with radiographic and functional findings

In 14 patients with biopsy-proved lymphangiomyomatosis, disease extent at computed tomography (CT) was correlated with findings at chest radiography and pulmonary-function testing. The CT scans and chest radiographs were read independently by two chest radiologists. Disease extent was assessed on CT scans by using a visual score (0%-100% involvement of the lung parenchyma) and on radiographs by using an adaptation of the International Labour Office classification of the pneumoconioses. There was good concordance between the two observers for CT and radiographic scores (Kendall tau greater than or equal to .86, P less than .01). A significant but relatively low correlation was present between CT findings and radiographic severity of disease (r = .59, P less than .05). Impairment in gas exchange as assessed with the diffusing capacity correlated better with disease extent seen on CT scans (r = .69) than with chest radiographic findings (r = .59). Three patients had evidence of parenchymal disease on the CT scans but not on the radiographs. In one patient CT findings were negative despite a positive finding on chest radiographs. The authors conclude that CT is superior to chest radiography in the assessment of patients with lymphangiomyomatosis.     

Factors affecting place of death of hospice and non-hospice cancer patients.

We identified factors associated with death at home for 28,828 hospice and non-hospice cancer patients in 13 counties of western Washington State. Hospice participation was found to be the variable most strongly associated with death at home. Admission to hospice appears to override the tendency for certain subgroups of patients, such as the extreme elderly and those diagnosed close to death, to die in an institutional setting. These findings are discussed with respect to the problem of selection bias.     

Progression of human breast cancers to the metastatic state is linked to hydroxyl radical-induced DNA damage.

Hydroxyl radical damage in metastatic tumor DNA was elucidated in women with breast cancer, and a comparison was made with nonmetastatic tumor DNA. The damage was identified by using statistical models of modified base and Fourier transform-infrared spectral data. The modified base models revealed a greater than 2-fold increase in hydroxyl radical damage in the metastatic tumor DNA compared with the nonmetastatic tumor DNA. The metastatic tumor DNA also exhibited substantially greater base diversity than the nonmetastatic DNA, and a progression of radical-induced base damage was found to be associated with the growth of metastatic tumors. A three-dimensional plot of principal components from factor analysis, derived from infrared spectral data, also showed that the metastatic tumor DNA was substantially more diverse than the tightly grouped nonmetastatic tumor DNA. These cohesive, independently derived findings suggest that the hydroxyl radical generates DNA phenotypes with various metastatic potentials that likely contribute to the diverse physiological properties and heterogeneity characteristic of metastatic cell populations.     

Isolation of an abnormal protein C molecule from the plasma of a patient with thrombotic diathesis

Protein C has been purified from the plasma of a patient with thrombotic diathesis. Both before and after isolation, the protein showed reduced capacity to hydrolyze synthetic substrates and to anticoagulate plasma. Proteolysis with the soluble thrombin- thrombomodulin complex proceeded normally and to completion as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting. Approximately one-third of the protein is functional, indicating a heterozygous defect. Indirect studies suggest that the abnormal component can bind to protein S and phospholipids. Both forms of activated protein C can also incorporate radiolabeled diisopropylfluorophosphate.     

Inhibition of tissue factor/factor VIIa activity in plasma requires factor X and an additional plasma component

A study was carried out to explore requirements for the inhibition of tissue factor-factor VIIa enzymatic activity in plasma. Reaction mixtures contained plasma, 3H-factor IX or 3H-factor X, tissue factor (vol/vol 2.4% to 24%), and calcium. Tissue factor-factor VIIa activity was evaluated from progress curves of activation of factor IX or factor X, plotted from tritiated activation peptide release data. With normal plasma, progress curves exhibited initial limited activation followed by a plateau indicative of loss of tissue factor-factor VIIa activity. With hereditary factor X-deficient plasma treated with factor X antibodies, progress curves revealed full factor IX activation. Adding only 0.4 micrograms/mL factor X (final concentration) could restore inhibition. Inhibition was not observed in purified systems containing 6% to 24% tissue factor, factor VII, 0.5 micrograms/mL, factor IX, 13 micrograms/mL, and factor X up to 0.8 micrograms/mL, but could be induced by adding barium-absorbed plasma to the reaction mixture. Thus, both factor X and an additional material in plasma were required for inhibition. The amount of factor X needed appeared related to the concentration of tissue factor; adding more tissue factor at the plateau of a progress curve induced further activation. These results also indicate that inhibited reaction mixtures contained active free factor VII(a). Preliminary data suggest that inhibition may stem from loss of activity of the tissue factor component of the tissue factor- factor VII(a) complex.