Screening test for early detection of colorectal cancer

Details Screening test for early detection of colorectal cancer Screening test for early detection of colorectal cancer

1999-03-16

2001-02-13

Warden, Jill (Department: 1743)

Chemistry: analytical and immunological testing

Biological cellular material tested

C436S064000, C436S166000, C436S169000, C436S128000, C436S164000, C435S040510

Reexamination Certificate

active

06187591

ABSTRACT:

FIELD OF THE INVENTION
This invention relates to a simple screening test for colorectal cancer whereby a marker is detected in rectal mucus. More particularly, this marker is detected in the mucus deposited on a support using Schiff's reagent.
BACKGROUND OF THE INVENTION
Colorectal carcinoma is the second most frequent cause of cancer mortality in men and women, causing nearly one third of all malignancy-related deaths in North America. It has been estimated that ultimately as many as 6% of Canadians and Americans will develop malignancy in the lower bowel, and over 50% of them will die within 5 years of diagnosis. Many authorities believe that colorectal cancer can be controlled only by preventive measures (1) because there are no realistic prospects of significantly improving the cure rate once the cancer has spread beyond the bowel wall.
Primary prevention, i.e. averting the development of the tumour by altering biological risk factors, is not yet feasible since so little is understood of the etiology of the disease. Alternatively, secondary preventive measures, i.e. detection at an asymptomatic, treatable state, would be possible should an effective screening test be available. Indeed, neoplasms of the lower bowel have the characteristics that make them suitable candidates for the development of a screening test. This is because (i) they are a common cause of cancer-related deaths, and (ii) whereas once the stage of true cancer is reached, and showing symptoms, the mortality rate is over 50%. Removal of bowel neoplasms at their earliest, asymptomatic stage can be done by non-surgical endoscopic polypectomy, without any significant risk. Moreover, it requires at least four to six years before an adenomatous polyp reaches the cancer stage, so there is ample opportunity to detect these neoplasms at their treatable stage. Recent clinical studies document a decrease in mortality in consequence of colorectal cancer screening, as predicted by these theoretical considerations. The problem to-date has been that polyps can be reliably detected only by endoscopy.
Thus, colorectal cancer satisfies each of the following three criteria of a disease considered suitable for a screening program. First, it is a relatively common condition with serious consequences. Second, curative treatment is available when detected at an early stage, i.e. snare polypectomiy through a colonoscope or surgical segmental bowel resection. Third, the prevalence is sufficiently high to justify the expense of a screening program (2).
Principles of Screening
The goal of a medical screening program is to reduce morbidity and mortality by detecting a disease at a sufficiently early stage to allow curative treatment. It is not designed necessarily to diagnose a disease, but to determine which asymptomatic, apparently disease-free individuals should undergo diagnostic interventions. The ability of a screening test to distinguish those who warrant further evaluation from those who do not is expressed in epidemiological terms. The term “sensitivity” is defined as the proportion of diseased individuals who have a positive test, i.e. the proportion of true positives/relative to all persons with the disease. “Specificity” is the proportion of disease-free subjects who have a negative test, i.e. the proportion of true negatives/relative to persons without the disease. The term “positive predictive value” is the proportion of positive tests due to the disease, i.e. the proportion of true positives/relative to all positives. Almost always, sensitivity and specificity must be traded against each another. Intuitively, it appears wise to design a screening test for a fatal disease so as to optimize sensitivity, in order to detect as many individuals with the disease as possible. It is emphasized, however, that optimizing sensitivity brings with it a risk of reducing specificity to such an extent that unacceptably high costs, poor compliance, and “flooding” of diagnostic facilities result. Moreover, positive predictive value, which is a particularly useful expression of the value of a screening test, is critically dependent on specificity and on the prevalence of the disease in the population screened.
It has been stressed that the effectiveness of a screening test can be properly evaluated only by randomized controlled trials. In the case of cancer, it is not sufficient to demonstrate that life is prolonged when the malignancy is detected by a positive screening test, compared to when the tumour is diagnosed after the development of symptoms. Instead, it must be shown that screened individuals have a lower death rate from the malignancy than similar individuals not enrolled in such a screening program. A particularly fallacious assumption is that the predictive value of a screening test is the same in a hospitalized population with advanced disease, in which the test is usually initially tried, as it is in a healthy population with early minimal disease, to which the test is usually aimed.
Current Population Screening Methods
Endoscopic methods, such as sigmoidoscopy or entire-length colonoscopy, are diagnostic rather than screening techniques, although sigmoidoscopy is sometimes used for screening. The only current method of colorectal cancer screening in the general population is searching for occult blood in the stool (3). Present techniques e.g. HemOccult II which involves smearing a sample of stool onto guaiac-impregnated paper which, after treatment with hydrogen peroxide containing developer, exhibits blue colour if blood (haemoglobin) is present. After almost two decades of experience with this methodology, it has become clear that even in expert centres, the sensitivity is less than 50% for curable neoplasms, and that the positive predictive value approximates, at best, only 40% in a clinic population. An update from the large-scale (n=97, 205) University of Minnesota, Minnesota, United States, prospective trial indicates a positive predictive value for colorectal cancer of only 2.2% (4). Furthermore, factors such as medications, multiple dietary constituents, delays in specimen handling, variabilities in fecal hydration, and storage of assay materials, commonly confound results. Analysis of one of the three randomized controlled studies assessing the value of HemOccult suggests comparable mortality rates in the screened and control populations (5). Newer methods of detecting occult blood, e.g. methods based either on porphyrin analysis [HemoQuant] or antibody specific for human haemoglobin, improve on these results. However, three limiting problems remain unlikely to be overcome. These are that colorectal malignancies shed blood only intermittently, upper gastrointestinal tract bleeding may make the results falsely positive, and multiple lesions in the lower bowel, apart from colorectal neoplasms, commonly bleed. Such lesions include hemorrhoids, diverticulae, ulcers, and vascular ectasie. Compliance in unselected populations has been estimated to be less than 30%, at least partly because the technique requires patients, themselves, to smear their stool onto a slide or a strip, a task most people find not only distasteful, but also technically difficult. Despite this, HemOccult continues to be widely used because the American Cancer Society has recommended occult blood testing yearly for all individuals over 50 years of age, arguing that even an imperfect test will save many lives. Implicit in all arguments over the value of HemOccult is that any improvement in screening techniques for bowel malignancy would have a dramatic impact on colorectal cancer mortality rates, since the screening for occult blood even in the present form leads to reducing mortality from colorectal cancer (6).
Experimental Screening Methods
(i) Screening for colorectal cancer by stool DNA analysis (7). This is based on the presence in stool of neoplastic cells shed in large numbers into the colonic lumen. In principle, a mutation which is common to neoplasms could be detected with high precision by analyzing DNA from thes

Affiliated with

Also associated with

Rating

Screening test for early detection of colorectal cancer does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Screening test for early detection of colorectal cancer, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Screening test for early detection of colorectal cancer will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2569357