Cancer-related Disparities: Weathering the Perfect Storm Through Comprehensive Cancer Control Approaches

During the last two decades extraordinary progress in developing and using effective cancer prevention strategies, early detection interventions, and cancer treatments has been made. This progress has resulted in an overall decline in mortality rates for all cancers combined. Nonetheless, cancer is the second most common cause of death in the United States. Although cancer is a diagnosis that many survive, cancer experiences across populations may vary considerably. These differences in cancer experiences have created an unequal disease burden that presents distinct professional and moral challenges to our nation. Many cancer control plans suggest specific strategies that prioritize eliminating cancer-related disparities. This article describes certain cancer-related disparities in the United Sates and gives several examples of how communities and disenfranchised populations are using comprehensive cancer control (CCC) approaches to eliminate these disparities. One or two interventions are highlighted in each example.     

DNA flow-cytometric analysis in colorectal cancer: A comparison of metastasizing and non-metastasizing tumours

The most common cause of death in patients with colorectal cancer is metastatic liver disease. In order to identify patients at a high risk of developing hepatic secondaries from colorectal cancers, DNA content was measured in metastasizing colorectal primaries (Group I, n= 32) as well as in their subsequently resected liver secondaries and in sections of non-metastasizing colorectal cancers (Group II, n= 25). A modified interpretation system involving both a DNA index and percentage of cycling cells (those in S and G2 + M phases) was developed. DNA content was measured in paraffin-embedded sections by flow cytometry using internal controls (human peripheral blood mononuclear cells) and non-malignant tissue controls (19 patients with diverticular disease). In Group I there were significantly more tumours with both abnormal ploidy (aneuploid or abnormal tetraploid peak) and > 15% cycling cells compared with Group II (Chi-squared; P= 0.034). The combination of abnormal ploidy and > 15% cycling cells was superior to Dukes’ classification for identifying metastasizing tumours (Logistic Regression; P= 0.047). However, it was not possible to discriminate between the two groups using either DNA ploidy or the percentage of cycling cells alone. The metastasizing colorectal cancers exhibited similar DNA ploidy characteristics and had a similar percentage of cycling cells compared with their liver metastases. These results suggest that tumour DNA ploidy plus the percentage of cycling cells may predict the development of liver metastases and thus survival in patients with colorectal cancer.     

A survey of pre-placement urinalysis drug findings.

In December, 1989, the Department of Transportation (DOT) in conjunction with the Federal Aviation Administration (FAA) mandated an extensive urine drug testing program for selected positions within the airline industry. At the end of 1 year we have tested 7,872 applicants under these rules, with a positive finding rate of 0.17%. We have also tested 32,157 applicants, including those applying for DOT-covered positions, with a positive rate of 2.82%. Considering only the two major drugs of abuse--marijuana and cocaine--we found the positive rate to be an order of magnitude greater than the rate discovered under the DOT program. We present these data together with a discussion of some of the possible reasons for this major disparity. We also present findings for barbiturates and benzodiazepines which are not tested under the DOT program, but which have safety implications related to the aviation industry.     

The influence of cardiac geometry on the results of ventricular aneurysm repair.

Operative repair of ventricular aneurysms should improve left ventricular function. Despite its theoretic advantage, the mortality following this operation is high, and many patients have severe postoperative hypotension. The cardiac findings were studied in 18 patients who died after repair of ventricular aneurysms. All hearts were examined at autopsy after postmortem coronary arteriography and fixation in a distended state. Five patients in Group I had intractable fatal postoperative hypotension, 7 in Group II initially had severe hypotension that improved, and 6 in Group III did not have postoperative hypotension. Curvature thickness indexes (CTIs) of the ventricular segments, which correlate with their pressure-producing activity, were determined in the 18 hearts. CTIs for the left ventricular free wall and septum were lower in Group I and Group II patients with hypotension than those in Group III without. The reduced CTIs in patients with postoperative shock appear to arise as a result of ventricular reconstruction that reduces ventricular wall curvature. The authors suggest that left ventricular function after aneurysm resection would be improved by inverting, rather than everting, the edges of the ventriculotomy, thereby increasing wall curvature and the CTI. Noninvasive determinations of the CTI may prove of value in guiding topographic reconstruction of ventricles with aneurysms.     

ATRX encodes a novel member of the SNF2 family of proteins: mutations point to a common mechanism underlying the ATR-X syndrome

It was shown recently that mutations of the ATRX gene give rise to a severe, X-linked form of syndromal mental retardation associated with alpha thalassaemia (ATR-X syndrome). In this study, we have characterised the full-length cDNA and predicted structure of the ATRX protein. Comparative analysis shows that it is an entirely new member of the SNF2 subgroup of a superfamily of proteins with similar ATPase and helicase domains. ATRX probably acts as a regulator of gene expression. Definition of its genomic structure enabled us to identify four novel splicing defects by screening 52 affected individuals. Correlation between these and previously identified mutations with variations in the ATR-X phenotype provides insights into the pathophysiology of this disease and the normal role of the ATRX protein in vivo.      

Association of Helicobacter pylori infection with gastric cancer

BACKGROUND: Helicobacter pylori has generated public health interest since its identification in 1983. Past studies have suggested that the bacterium plays a role in the pathogenesis of gastric cancer. More recent studies support the conclusion that the association of H. pylori with gastric cancer is causal. The purpose of this article is to review the available evidence supporting the association of H. pylori with gastric cancer. METHODS: We performed a critical review of the relevant literature published in the English language on H. pylori and gastric cancer using MEDLINE, Index Medicus for the years 1985 to 1997. The reference lists of selected articles also were reviewed to capture citations for further pertinent studies. RESULTS: H. pylori is thought to be the major cause of chronic atrophic gastritis. H. pylori gastritis is worldwide in distribution. H. pylori is now categorized by the International Agency for Cancer Research as a group 1 carcinogen, i.e., an agent that is carcinogenic to humans. Several reports from the United States have found the highest frequencies of gastric cancer in geographic areas and populations with the highest rates of acquisition of H. pylori infection. The high prevalence of H. pylori infection has been documented most notably in blacks and Hispanics, who also are at high risk for gastric cancer. CONCLUSIONS: New studies that focus on the epidemiology and pathology of H. pylori improve our understanding of its relationship with gastric cancer and advance the development of gastric cancer prevention and control strategies that are proposed.     

Changes in intramyocardial ST segment voltage and gas tensions with regional myocardial ischemia in the dog.

This study was designed to evaluate the sensitivity of changes in myocardial carbon dioxide and oxygen tensions as indicators of regional myocardial ischemia and also to determine to what extent these changes can be related to changes in intramyocardial ST segment voltage. Changes in ST segment voltage recorded in unipolar epicardial electrodes proved to be a less-sensitive indicator of underlying myocardial ischemia than were changes in ST segment voltage recorded in unipolar intramyocardial electrodes. In 9 dogs, regional ischemia was produced by placing a variable constrictor on the left circumflex coronary artery; circumflex flow was monitored. Myocardial carbon dioxide and oxygen tensions were measured using a mass spectrometer. Unipolar electrograms were recorded using a multicontact plunge electrode. With progressive degrees of proximal stenosis, ranging from a critical stenosis, which is associated with a decrease in mean flow of less than 15%, to a severe stenosis associated with and 80% decrease, ST voltage increased 21 mv and carbon dioxide tension increased 84 mm Hg, but oxygen tension decreased only 7 mm Hg. The study suggests that increases in intramyocardial ST segment voltage, an index of myocardial ischemia, are associated with parallel increases in myocardial carbon dioxide tension, each providing a more sensitive quantitative correlate of regional myocardial ischemia than do decreases in oxygen tension. The local accumulation of carbon dioxide may be an important pathophysiological mechanism in myocardial ischemia.     

Electrical polarity in embryos of wild carrot precedes cotyledon differentiation

Endogenous electrical currents traverse embryos of a higher plant, the wild carrot Daucus carota L. Current enters the apical pole and leaves the region near the presumptive radicle in the radially symmetric globular embryo. Current also enters the exposed surfaces of incipient globular embryos. This electrical polarity precedes differentiation of vascular tissue and cotyledon development. Localized current is observed at both growing ends of the embryos in subsequent stages of embryogenesis. Inward current is found at the cotyledons; outward current is found at the radicle/root. Exogenous indole-3-acetic acid (3 μM) reversibly inhibits these currents. Little current traverses the surface of intermediate regions of the embryo. The ionic gradients generated by these currents may be important in accumulation of metabolites and in other developmental processes within the embryo.     

Aortic disease associated with pregnancy

Our experience with the management of two patients with life-threatening aortic disease during pregnancy is presented with a review of the literature. One of our patients had intimal disruption caused by trauma; the other had probable Ehlers-Danlos type IV syndrome, causing an acute dissection of the descending thoracic aorta and eventually requiring replacement of the aorta from the left subclavian artery to common iliac arteries. The challenge of treating both the pregnant woman and the fetus was managed successfully by an emergent cesarean section followed by Dacron graft replacement of the descending thoracic aorta. The literature reviewed disclosed that aneurysm expansion producing symptoms and dissection is most common during the third trimester and during labor and delivery in patients with or without Marfan's syndrome. Half of the aortic dissections in women less than 40 years of age occur in association with pregnancy. The available evidence indicates that patients with known valvular or aortic disease should have surgical repairs during the first or second trimester and thereafter have delivery by cesarean section. However, patients with acute aortic problems near term appear to be better managed by cesarean section followed promptly by treatment of the aortic disease.