Effect of aspirin and non-steroidal anti-inflammatory drugs on colorectal adenomas: case-control study of subjects participating in the Nottingham faecal occult blood screening programme.

OBJECTIVE--To examine the relation between the use of aspirin and non-steroidal anti-inflammatory drugs and the presence of asymptomatic colorectal adenomas. DESIGN--Case-control study of subjects participating in a randomised controlled trial of faecal occult blood screening for colorectal cancer. Data on analgesics and other drugs were obtained from a questionnaire which was mainly concerned with diet and was administered by an interviewer. SETTING--Nottingham. SUBJECTS--147 patients with positive results in faecal occult blood tests who were found to have colorectal adenomas (cases), 153 age and sex matched control subjects with negative results in such tests (negative controls), and 176 control subjects with positive results in the tests who were found not to have colorectal adenomas (positive controls). MAIN OUTCOME MEASURES--Relative risk of developing colorectal adenomas according to frequency and duration of use of analgesics. RESULTS--Cases reported taking less aspirin and non-steroidal anti-inflammatory drugs than the negative controls, with the estimated relative risk for any use being 0.49 (95% confidence interval 0.3 to 0.8). The inverse association was less strong when cases were compared with the positive controls (0.66 (0.4 to 1.1)). The association was specific for aspirin and non-steroidal anti-inflammatory drugs there being no association with paracetamol or other drugs. Prescribed use of non-steroidal anti-inflammatory drugs for longer than five years was associated with the lowest risk (0.21 (0.1 to 0.8)), although the numbers reporting prolonged prescribed use were small. CONCLUSIONS--These findings support the hypothesis that aspirin and non-steroidal anti-inflammatory drug use protects against the development of colorectal neoplasia.     

Impact of the UK colorectal cancer screening pilot studies on incidence, stage distribution and mortality trends

Objective: To assess the impact of the UK colorectal cancer guaiac faecal occult blood test screening pilot studies on incidence trends, stage distribution and mortality trends. Design: Ecological study. Setting: Scotland and the West Midlands. Data: We extracted anonymised colorectal cancer (ICD-10 C18–C20) registration (1982–2006) and death records (1982–2007), along with corresponding mid-year population estimates. Intervention: Residents of the screening pilot areas, in the age group 50–69 years, were offered biennial guaiac faecal occult blood test screening from 2000 onwards. Screening was not offered routinely in non-pilot areas until the start of the roll-out of the national screening programmes in England and in Scotland in 2006 and 2007, respectively. Main outcome measures: We analysed trends in age-specific incidence and mortality rates, and Dukes’ stage distribution. Within each country/region, we compared the screening pilot areas to non-screening pilot (‘control’) areas using Chi square tests and Poisson regression modelling. Results: Following the start of the screening pilots, as expected in the prevalent round of a new screening programme, in the pilot areas there was a short-lived increase in incidence of colorectal cancer among 50–69 year olds except for females in the West Midlands. A trend towards earlier stage and less advanced disease was also observed, with males showing significant increases in Dukes’ A and corresponding decreases in Dukes’ C in the screening pilot areas (all P < 0.03). With the exception of females in the West Midlands, mortality rates for colorectal cancer decreased significantly and at a faster rate in the populations invited for screening. Conclusion: The existence of a natural control population not yet invited for screening provided a unique opportunity to assess whether the benefits of colorectal cancer screening, beyond the setting of a randomised controlled trial, could be detected using routinely collected statistics. Our analysis suggests that screening will fulfil its aim of reducing mortality from colorectal cancer.     

Screening and self examination for breast cancer.

Breast cancer is the major form of cancer in women, with nearly 30,000 new cases and over 15,000 deaths in the United Kingdom each year. Breast screening by mammography has been shown in randomised trials to reduce mortality from breast cancer in women aged 50 and over. An NHS breast screening programme has been in operation in the United Kingdom since 1988. Its aim is to reduce mortality from breast cancer by 25% in the population of women invited to be screened. The uptake of mammography among the eligible population may be the single most important determinant if the programme is to be effective. Primary care teams have an important part to play in encouraging women to attend for screening and in providing information, advice, and reassurance at all stages of the screening process. To date, routine breast self examination has not been shown to be an effective method of screening for breast cancer and should not therefore be promoted as a primary screening procedure. There is, however, a case to be made for women to become more "breast aware."     

Influence of non-steroidal anti-inflammatory drugs on the outcome of faecal occult blood tests in screening for colorectal cancer.

Non-steroidal anti-inflammatory drugs have been accused of causing false positive results in faecal occult blood tests for colorectal cancer. A study was therefore performed in 10,931 people undergoing faecal occult blood screening tests to assess the effect of these drugs on the predictive value of a positive test result. Those with a positive result were interviewed and a full drug history was taken before they underwent a full colorectal examination. Of the 455 people with a positive result, 50 were taking non-steroidal anti-inflammatory drugs: 10 (20%) had colonic neoplasia. Of the 405 who were not taking non-steroidal anti-inflammatory drugs, 129 (32%) had colonic neoplasia. These detection rates were not significantly different, and the predictive value of a positive result for an adenoma larger than 1 cm was 14% in the group not taking anti-inflammatory drugs and 26% in the group taking them (not significant). These results suggest that a finding of occult faecal blood cannot be attributed to upper gastrointestinal tract bleeding caused by non-steroidal anti-inflammatory drugs and should be followed by a thorough colorectal examination.     

Modeling and optimization in early detection programs with a single exam

The choice of timing of screening examinations is an important element in determining the efficacy of strategies for the early detection of occult disease. In this article, we describe a flexible decision-making framework for the design of early detection programs, and we investigate the choice of timing when each individual in the screening program is examined only once. We focus on the theoretical relation between the optimal examination time and the distributions of sojourn times in health-related states. Specifically, we derive closed-form solutions of the optimal age using two specifications of utility functions, discuss the effects of natural history and utility specifications on the optimal solution, and present an application to early detection of colorectal cancer by once-only sigmoidoscopy or colonoscopy.     

Clinical Experience with Flexible Sigmoidoscopy in Asymptomatic and Symptomatic Patients

The purpose of this study was to evaluate the diagnostic yield of flexible sigmoidoscopy when performed as a routine procedure in asymptomatic patients over the age of 40 being referred for a complete physical examination. The preliminary results of this ongoing program are presented together with the diagnostic yield in 408 patients with symptoms and signs suggestive of colorectal disease who were of similar age (56.6 vs. 56.5 years) and sex distribution (79 percent male) to the asymptomatic population, and who underwent flexible sigmoidoscopy as an indicated part of their evaluation. In the 122 asymptomatic patients, the mean distance examined by the procedure was 50.8 cm with the instrument being advanced beyond the optimal rigid sigmoidoscopy distance of 20 cm in 100 percent of patients. Adenomatous and hyperplastic polyps were identified in 16 patients, 13.1 percent, in the asymptomatic group, a similar percentage to the symptomatic population, 15.4 percent. Adenomatous polyps were diagnosed in 7.4 percent of the asymptomatic subjects and 9.1 percent of the symptomatic group. Colonic cancer was diagnosed in 0.8 percent of asymptomatic patients vs. 3.2 percent of the symptomatic group (p < 0.05). Seventy-seven percent of the neoplastic polyps detected in the asymptomatic patients and 60 percent in the symptomatic group were beyond 20 cm from the anus. Diverticulosis was diagnosed in a similar percentage of patients, 13.1 percent in the asymptomatic and 10.0 percent in the symptomatic group. No complications were encountered and the procedure was well tolerated without analgesia. It is concluded that: (1) in an asymptomatic population over the age of 40, flexible sigmoidoscopy, as a routine examination, results in a diagnostic yield not possible with rigid proctosigmoidoscopy and which approaches that observed in a symptomatic population of similar age; (2) for the internist trained in this procedure, flexible sigmoidoscopy has a future role in the detection of colorectal lesions and as an interval screening examination for premalignant lesions and colorectal cancer in asymptomatic and symptomatic patients.     

Impact of an educational video-based strategy on the behavior process associated with colorectal cancer screening: A randomized controlled study

Background: Low public awareness is an important barrier for colorectal cancer screening participation. Aim: To evaluate the impact of educational intervention on the health behavior process, patient knowledge and compliance with colorectal cancer screening in the average-risk population. Methods: 158 subjects (aged 50–79 years) were randomly assigned either to watch a non-medical video or a colorectal cancer educational video. Before and after watching the experimental or control videotape, participants completed a five-item questionnaire that assessed their knowledge about risk factors for colorectal cancer, age of risk, warning symptoms, 5-year prognosis, and incidence. Subjective risk perception for developing colorectal cancer, barriers or benefits of screening, and intention to be screened were also investigated. Finally, subjects received a faecal occult blood test kit and were requested to use and return it within 2 weeks. Results: Participants in the video-based intervention group showed significant improvement in knowledge of colorectal cancer scores (P < 0.001) and decreased barrier scores. The intervention group returned significantly more faecal occult blood tests than controls (69.6% vs. 54.4%, P = 0.035). The intervention had a positive effect on modifying attitudes and intention to take part in screening. Additionally, the intervention was a predictor of compliance (OR 2.0; 95% CI = 1.02–3.84, P = 0.044). Conclusion: Video-based intervention significantly reduced barriers to screening and improved participant awareness and compliance with colorectal cancer screening with faecal occult blood test.     

Use of RNA isolated from feces as a promising tool for the early detection of colorectal cancer

Colorectal cancer is one of the most common forms of cancer worldwide. Early detection would allow patients to be treated surgically and halt the progression of the disease; however, the current methods of early detection are invasive (colonoscopy and sigmoidoscopy) or have low sensitivity (fecal occult blood test). The altered expression of genes in stool samples of patients with colorectal cancer can be determined by RT-PCR. This is a noninvasive and highly sensitive technique for colorectal cancer screening. According to information gathered in this review and our own experience, the use of fecal RNA to determine early alterations in gene expression due to malignancy appears to be a promising alternative to the current detection methods and owing to its low cost could be implemented in public health services.     

Screening and genetic counselling for relatives of patients with colorectal cancer in a family cancer clinic.

OBJECTIVE--To introduce and monitor a screening programme for first degree relatives of patients with colorectal cancer based on their calculated lifetime risk. DESIGN--Lifetime risks were calculated for first degree relatives of patients with colorectal cancer and used to offer screening based on estimated risk. SETTING--A family cancer clinic was set up as part of the North East Thames Regional Genetic Service for relatives of patients who had developed colorectal cancer before the age of 45 and members of families in which multiple cancer had occurred. PATIENTS--Self referrals as well as patients referred by general and hospital practitioners. INTERVENTION--Relatives with a lifetime risk of 1 in 10 or greater (high risk group) were offered screening five yearly by colonoscopy, and those whose risk was between 1 in 10 and 1 in 17 were offered yearly screening for faecal occult blood. Women with family histories compatible with Lynch type II cancer family syndrome were offered screening for breast and pelvic tumours. RESULTS--In four years 715 patients were seen. Acceptance of screening was 90% (644 patients). Of 151 patients screened for faecal occult blood, two were found to have polyps. This screening test was unsatisfactory for the high risk group, having a negative predictive value of 78% in 59 patients tested. Regular screening by colonoscopy was offered to 382 high risk patients; 62 patients with polyps and five with colonic cancer were found. One hundred and ten pedigrees were identified with the Lynch type II cancer family syndrome, and four of 35 women screened were found to have breast cancer. Of 14 relatives aged over 65 with a 1 in 2 risk of site specific colonic cancer or Lynch type II cancer family syndrome, seven were found to have polyps, one of whom had carcinoma in situ. CONCLUSIONS--Family history can be used to identify those at risk of colonic cancer and to target appropriate screening. Colonoscopy detected a high number of premalignant colonic polyps, but faecal occult blood testing was unsatisfactory for those at high risk of colorectal cancer.     

Use of the Analysis of the Volatile Faecal Metabolome in Screening for Colorectal Cancer

Diagnosis of colorectal cancer is an invasive and expensive colonoscopy, which is usually carried out after a positive screening test. Unfortunately, existing screening tests lack specificity and sensitivity, hence many unnecessary colonoscopies are performed. Here we report on a potential new screening test for colorectal cancer based on the analysis of volatile organic compounds (VOCs) in the headspace of faecal samples. Faecal samples were obtained from subjects who had a positive faecal occult blood sample (FOBT). Subjects subsequently had colonoscopies performed to classify them into low risk (non-cancer) and high risk (colorectal cancer) groups. Volatile organic compounds were analysed by selected ion flow tube mass spectrometry (SIFT-MS) and then data were analysed using both univariate and multivariate statistical methods. Ions most likely from hydrogen sulphide, dimethyl sulphide and dimethyl disulphide are statistically significantly higher in samples from high risk rather than low risk subjects. Results using multivariate methods show that the test gives a correct classification of 75% with 78% specificity and 72% sensitivity on FOBT positive samples, offering a potentially effective alternative to FOBT.     

Screening for cancer.

Screening has proved effective for only two cancer sites, the breast and the cervix uteri. Only for these, therefore, should screening be a part of routine clinical practice. The degree to which screening is effective depends on whether appropriate groups are screened. For cancer of the breast, current evidence justifies mammographic screening every two years only from the age of 50, continuing at least to the age of 70. The place of breast self-examination and physical examination of the breasts is under investigation, but these procedures should probably be used in all women after the age of 40. For cancer of the cervix, nearly maximal efficacy is obtained by screening sexually active women every three years from the age of 25 to 60. Older women who have not been screened regularly should be screened. Other screening techniques to detect cancers, such as the rectal examination, sigmoidoscopy, and fecal occult blood tests for colorectal cancer, are still experimental. Organizational and other difficulties will prevent screening programs from making a major contribution to reducing overall cancer mortality by the year 2000. If organizational problems can be overcome, however, screening may control invasive cancer of the cervix and make a major contribution in reducing breast cancer mortality in the future.     

Cancer: improving early detection and prevention. A community practice randomised trial.

OBJECTIVE--To test the impact of physician education and facilitator assisted office system interventions on cancer early detection and preventive services. DESIGN--A randomised trial of two interventions alone and in combination. SETTING AND SUBJECTS--Physicians in 98 ambulatory care practices in the United States. INTERVENTIONS--The education intervention consisted of a day long physician meeting directed at improving knowledge, attitudes, and skills relevant to cancer prevention and early detection. The office system intervention consisted of assistance from a project facilitator in establishing routines for providing needed services. These routines included division of responsibilities for providing services among physicians and their staff and the use of medical record flow sheets. MAIN OUTCOME MEASURES--The proportions of patients provided the cancer prevention and early detection services indicated annually according to the US National Cancer Institute. RESULTS--Based on cross sectional patient surveys, the office system intervention was associated with an increase in mammography, the recommendation to do breast self examination, clinical breast examination, faecal occult blood testing, advice to quit smoking, and the recommendation to decrease dietary fat. Education was associated only with an increase in mammography. Record review for a patient cohort confirmed cross sectional survey findings regarding the office system for mammography and faecal occult blood testing. CONCLUSION--Community practices assisted by a facilitator in the development and implementation of an office system can substantially improve provision of cancer early detection and preventive services.     

Evaluation of a proposed breast cancer screening regimen.

The Forrest working group on breast cancer screening recommended routine mammography for women in the United Kingdom at ages 50, 53, 56, 59, 62, and 65. Benefits were costed at about 3000 pounds for each life year recovered, but there was no estimate of the cost of each life saved, and the consequent reduction in mortality from breast cancer in the general population of the United Kingdom was not estimated. The present study addressed both of these issues using an interactive computer modelling process. Long term savings were calculated at 900 deaths a year in England and Wales--that is, about 8% of the total deaths from breast cancer--and 9% of life years currently lost. The cost of each death saved from breast cancer was estimated at 39,000 pounds.     

Carcinoma of the Colon and Rectum: A Perspective for Practicing Physicians,with Recommendations for Screening

Carcinoma of the colon and rectum is the most common serious type of cancer found in the United States and is second only to lung cancer among causes of death from cancer. Its cause is unknown but several environmental factors—especially low bulk, high fat diets—seem to predispose to its development. The disease is readily treatable by surgical operation if it is diagnosed early. Radiation and chemotherapy may offer some additional benefit in treating advanced disease but the response to all forms of therapy is disappointing in patients in whom disease has spread beyond the bowel wall. Colorectal cancer appears to be a very slowly progressive disease with a long asymptomatic period providing an ideal opportunity for diagnosis at an early treatable stage. Both proctosigmoidoscopy and screening specimens of stool for occult blood have been shown to be effective methods for identifying it before symptoms develop. These procedures should be done routinely in all patients over 40 years old and especially in those patients who have other risk factors such as positive family histories or hereditary conditions known to predispose to colorectal cancer.     

A projection of benefits due to fecal occult blood test for colorectal cancer

Objectives: A prospective study to estimate benefits due to fecal occult blood tests for colorectal cancer are carried out for both males and females, under different screening frequencies. Methods: We apply the statistical method developed by Wu et al. (2007) [1] using the Minnesota colorectal cancer study group data, to make Bayesian inference for the lead time, the time of diagnosis advanced by screening for both male and female participants in a periodic screening program. The lead time is distributed as a mixture of a point mass at zero and a piecewise continuous distribution. The two parts of the mixture correspond to two aspects of the screening: the probability of no benefit, or the percentage of interval cases; and the probability distribution of the early diagnosis time. We present estimates of these two measures for males and females by simulation studies using the Minnesota study group data. We also provide the mean, mode, variance, and density curve of the program's lead time by gender. This may provide policy makers important information on the effectiveness of the FOBT screening in colorectal cancer early detection. Results: The mean lead time increases as the screening time interval decreases for both males and females. The standard error of the lead time also increases as the screening time interval decreases for both genders. Females seem get more benefit than males, in that females usually have a longer lead time than males if both take the test at the same time interval and the lead time mode for females is greater than that of males in the same screening time interval. Conclusion: According to the predictive estimation of the lead time distribution, to guarantee a 90% chance of early detection, it seems necessary for the males to take the fecal occult blood test every 9 months, while the females can take it annually.     

Evaluating the long-term effect of FOBT in colorectal cancer screening

BackgroundCancer screening has been effective in detecting tumors early before symptoms appear. However, the effectiveness of the regular fecal occult blood test (FOBT) in colorectal cancer in the long term has not been quantified.MethodsWe applied the statistical method developed by Wu and Rosner [1] using data from the Minnesota Colon Cancer Control Study (MCCCS). All initially asymptomatic participants were classified into four mutually exclusive groups: true-early-detection, no-early-detection, over-diagnosis, and symptom-free life; human lifetime was treated as a random variable and is subject to competing risks. All participants in the screening program will eventually fall into one of the four outcomes above. Predictive inferences on the percentages of the four outcomes for both genders were made using the Minnesota study data.ResultsDepending on gender, screening frequency and age at the initial screening, for all participants the probability of “symptom-free-life” varies between 95.3% and 96.6%; the probability of “true-early-detection” is 1.9–3.8%; the probability of no-early-detection is 0.3–2.0%; the probability of over-diagnosis is 0.16–0.3%. Among those with colorectal cancer detected by regular FOBT, the probability of over-diagnosis is lower than expected and is between 6% and 9%, with 95% CI (2.5%, 21.3%) for females and (1.9%, 44.7%) for males. The probability of true-early-detection increases as screening interval decreases. The probability of no-early-detection decreases as screening interval decreases.ConclusionThe probability of over-diagnosis among the screen-detected cases is not as high as previously thought. We hope this outcome can provide valuable information on the effectiveness of the FOBT in colorectal cancer detection in the long term.     

Training Primary Care Physicians in Flexible Sigmoidoscopy—Performance Evaluation of 17, 167 Procedures

The flexible fiber-optic sigmoidoscope is rapidly replacing the rigid sigmoidoscope in routine screening for colorectal cancer. This study was undertaken to evaluate the safety, usage pattern, and efficacy of fiber-optic sigmoidoscopy by evaluating the outcome of training and the results of procedures carried out by a group of primary care physicians. Of 1,153 participants in one-day flexible sigmoidoscopy workshops, 764 (66%) returned questionnaires evaluating their experiences following this training. Of these, 438 physicians had obtained a flexible sigmoidoscope, used it frequently, and had done a total of 17,167 examinations. The average time of scope usage was nine months. Although additional supervised training was suggested at the time of the workshop, 68% of physicians began doing flexible sigmoidoscopy without it. A total of 465 polyps and 153 cancers were detected by the study group for an overall detection rate of 2.7% for polyps and 0.9% for cancers. Four complications were reported. This study indicates that the technique of flexible sigmoidoscopy is readily learned, is diagnostically productive, and is reasonably safe in the hands of primary care physicians.     

Xeromammography in the Early Detection of Breast Cancer: Community Hospital Experience and Approach

Community hospitals can do much in the general effort toward earlier detection of breast cancer. Using xeromammography in the department of general radiology of one community hospital, 21 cases of occult carcinoma were detected in 2,392 patients in a two year period. Patients were both symptomatic and asymptomatic. This percentage is comparable to results in previously published series of similar patient populations, and can be expected to be slightly higher than screening populations of totally asymptomatic patients. In 24 percent of cases of occult carcinoma there was axillary node involvement, compared with 42 percent axillary node involvement in cases of nonoccult carcinoma.Early detection efforts are currently centered on improving thoroughness in physical examinations, stressing breast self-examination and identifying patients in high-risk categories. These, together with proper periodic use of mammograms, will yield the highest rate of early carcinoma detection until more sensitive biologic markers are developed.     

Improved screening for colorectal cancer by immunological detection of occult blood

A radial immunodiffusion technique for detecting faecal haemoglobin and the Hemoccult II kit used with and without rehydration of the faecal sample were compared in a screening programme for bowel cancer, in which 1328 subjects took part.A positive result was obtained in 170 (13%) subjects. Nineteen of the 153 subjects investigated were found to have colorectal carcinomas and 52 had polyps (40 with adenomas). Radial immunodiffusion and Hemoccult II with and without rehydration detected bleeding in, respectively, all 19, 15, and 11 subjects with colorectal carcinoma. Hemoccult II with and without rehydration detected only seven and six, respectively, of 11 Dukes''s stage A carcinomas, whereas all 11 were detected with the immunological test. Hemoccult II with and without rehydration and radial immunodiffusion detected bleeding from adenomas in, respectively, 22, 14, and 34 of the 40 subjects. False positive results occurred in 55 out of 1302 subjects by Hemoccult II with rehydration, in 28 out of 1304 by Hemoccult II without rehydration, and in 50 out of 1304 by the immunological technique; true positive results were defined as bleeding from carcinomas and adenomas.Immunological detection of occult blood in faecal samples seems to show more adenomas and carcinomas (particularly early lesions) than the Hemoccult II kit and has a rate of false positive results that is acceptably low.     

The Impact of Age,Sex and Socioeconomic Deprivation on Outcomes in a Colorectal Cancer Screening Programme

Background

Population-based colorectal cancer screening has been shown to reduce cancer specific mortality and is used across the UK. Despite evidence that older age, male sex and deprivation are associated with an increased incidence of colorectal cancer, uptake of bowel cancer screening varies across demographic groups. The aim of this study was to assess the impact of age, sex and deprivation on outcomes throughout the screening process.

Methods

A prospectively maintained database, encompassing the first screening round of a faecal occult blood test screening programme in a single geographical area, was analysed.

Results

Overall, 395 096 individuals were invited to screening, 204 139 (52%) participated and 6 079 (3%) tested positive. Of the positive tests, 4 625 (76%) attended for colonoscopy and cancer was detected in 396 individuals (9%). Lower uptake of screening was associated with younger age, male sex and deprivation (all p<0.001). Only deprivation was associated with failure to proceed to colonoscopy following a positive test (p<0.001). Despite higher positivity rates in those that were more deprived (p<0.001), the likelihood of detecting cancer in those attending for colonoscopy was lower (8% most deprived vs 10% least deprived, p = 0.003).

Conclusion

Individuals who are deprived are less likely to participate in screening, less likely to undergo colonoscopy and less likely to have cancer identified as a result of a positive test. Therefore, this study suggests that strategies aimed at improving participation of deprived individuals in colorectal cancer screening should be directed at all stages of the screening process and not just uptake of the test.