Review article: Population screening for colorectal cancer

Colorectal cancer is a common cancer and common cause of death. The mortality rate from colorectal cancer can be reduced by identification and removal of cancer precursors, adenomas, or by detection of cancer at an earlier stage. Pilot screening programmes have demonstrated decreased colorectal cancer mortality; as a result many countries are developing colorectal cancer screening programmes. The most common modalities being evaluated are faecal occult blood testing, flexible sigmoidoscopy and colonoscopy. Implementation of screening tests has been hampered by cost, invasiveness, availability of resources and patient acceptance. New technologies such at computed tomographic colonography and stool screening for molecular markers of neoplasia are in development as potential minimally invasive tools. This review considers who should be screened, which test to use and how often to screen.     

Review article: faecal occult blood testing for colorectal cancer

Major health organizations recommend colorectal cancer screening using faecal occult blood tests, sigmoidoscopy or both for patients 50 years of age or older who are at average risk for colorectal cancer. However, no specific recommendations have been made regarding choice of test from among the tests currently or soon to be available. Therefore, to aid clinicians in rationally choosing a particular test for faecal occult blood, published data are reviewed regarding the performance characteristics, strengths and weaknesses of the various faecal occult blood tests. New studies suggest that immunochemical tests (e.g. HemeSelect) or a combination of sensitive guaiac tests and immunochemical tests (e.g. Hemoccult Sensa and HemeSelect) are the most sensitive, specific tests for detecting colorectal carcinoma and colorectal polyps ≥ 1 cm.     

A sensitive guaiac faecal occult blood test is less useful than an immunochemical test for colorectal cancer screening in a Chinese population

BACKGROUND: Colorectal cancer screening by guaiac faecal occult blood test has been shown to reduce the incidence and mortality of colorectal cancer in Western populations. The optimal faecal occult blood test, whether guaiac or immunochemical, for colorectal cancer screening in the Chinese population remains to be defined. AIM: To compare the performance characteristics of a sensitive guaiac-based faecal occult blood test (Hemoccult SENSA) and an immunochemical faecal occult blood test (FlexSure OBT) in a Chinese population referred for colonoscopy. METHODS: One hundred and thirty-five consecutive patients who were referred for colonoscopy and who met the study inclusion criteria took samples for the two faecal occult blood tests simultaneously from three successive stool specimens, with no dietary restrictions. All tests were developed and interpreted by a single experienced technician who was blind to the clinical diagnosis. The sensitivity, specificity and positive predictive value for the detection of colorectal adenomas and cancers were estimated for the two tests. RESULTS: The sensitivity, specificity and positive predictive value for the detection of significant colorectal neoplasia (adenomas > or = 1.0 cm and cancers) were 91%, 70% and 18% for Hemoccult SENSA and 82%, 94% and 47% for FlexSure OBT. The specificity and positive predictive value were significantly higher for FlexSure OBT than for Hemoccult SENSA (P < 0.001 and P = 0.016, respectively). Combining the positive results from both faecal occult blood tests did not improve the accuracy. CONCLUSION: The positive predictive value of the immunochemical faecal occult blood test for the detection of significant colorectal neoplasia was 29% better than that of the sensitive guaiac-based test. This may relate to the Chinese diet and requires further study. The poor specificity of the sensitive guaiac-based test, without dietary restriction, makes it less useful for colorectal cancer screening in a Chinese population.     

Should we be screening for colorectal cancer?

Mass population screening for asymptomatic neoplastic disease is now national policy in the UK for breast cancer and has been established for many years in the early diagnosis of carcinoma of the cervix. Cancer screening is based on the concept that treatment is more effective when the disease is localised and aims to detect it when it is at a less advanced clinico-pathological stage prior to the development of symptoms. Because colorectal cancer develops in benign adenomatous polyps which are often amenable to endoscopic resection, screening may both reduce the incidence of the disease as well as improving outcome from it. Flexible sigmoidoscopy screening focuses mainly on the detection of potentially malignant adenomas, their endoscopic removal producing a decrease in colorectal cancer incidence. It is a promising approach but conclusive data on effectiveness from a Medical Research Council-sponsored multicentre randomised controlled trial will not be available before 2006. Faecal occult blood testing aims to preferentially detect early stage invasive disease. Three randomised controlled trials of faecal occult blood screening show that the disease can be detected earlier in its development leading to reduced mortality from the disease--and that this is achieved at reasonable cost. The Department of Health is currently giving consideration to its national implementation.     

As tests evolve and costs of cancer care rise: reappraising stool-based screening for colorectal neoplasia

Background Colorectal cancer screening and treatment are rapidly evolving. Aims To reappraise stool‐based colorectal cancer screening in light of changing test performance characteristics, lower test cost and increasing colorectal cancer care costs. Methods Using a Markov model, we compared faecal DNA testing every 3 years, annual faecal occult blood testing or immunochemical testing, and colonoscopy every 10 years. Results In the base case, faecal occult blood testing and faecal immunochemical testing gained life‐years/person and cost less than no screening. Faecal DNA testing version 1.1 at $300 (the current PreGen Plus test) gained 5323 life‐years/100 000 persons at $16 900/life‐year gained and faecal DNA testing version 2 (enhanced test) gained 5795 life‐years/100 000 persons at $15 700/life‐year gained vs. no screening. In the base case and most sensitivity analyses, faecal occult blood testing and faecal immunochemical testing were preferred to faecal DNA testing. Faecal DNA testing version 2 cost $100 000/life‐year gained vs. faecal immunochemical testing when per‐cycle adherence with faecal immunochemical testing was 22%. Faecal immunochemical testing with excellent adherence was superior to colonoscopy every 10 years. Conclusions As novel biological therapies increase colorectal cancer treatment costs, faecal occult blood testing and faecal immunochemical testing could become cost‐saving. The cost‐effectiveness of faecal DNA testing compared with no screening has improved, but faecal occult blood testing and faecal immunochemical testing are preferred to faecal DNA testing when patient adherence is high. Faecal immunochemical testing may be comparable to colonoscopy every 10 years in persons adhering to yearly testing.     

From screening criteria to colorectal cancer screening: what can New Zealand learn from other countries?

New Zealand is currently exploring how population-based colorectal cancer (CRC) screening will be implemented. The United Kingdom (UK), Australia, France, Italy, Spain, Finland, Denmark, the Netherlands, and Switzerland have conducted or are currently conducting pilot/feasibility studies. The UK, Australia, Finland, Canada, France and Italy are all in the early stages of implementing population-based CRC screening programmes. Most of these countries have lower CRC mortality rates than New Zealand. New Zealand is in a good position to learn from this overseas experience. Some of the key areas that will require careful consideration include; the best use of a population register to identify and invite eligible participants; the type of screening test to be used; ensuring adequate colonoscopy capacity; efficient and effective information systems; the management of high-risk groups; and how to ensure that all population groups benefit from screening.     

Screening, prevention and socioeconomic costs associated with the treatment of colorectal cancer

Colorectal cancer (CRC), the third most prevalent cancer worldwide, imposes a significant economic and humanistic burden on patients and society. One study conservatively estimated the annual expenditures for colorectal cancer to be approximately dollars US 5.3 billion in 2000, including both direct and indirect costs. However, other investigators estimated inpatient costs alone incurred in the US in 1994 to be around dollars US 5.14 billion. Therefore, the economic burden of colorectal cancer in the US could be projected to be somewhere in the range of dollars US 5.5-6.5 billion by considering that inpatient costs approximate 80% of total direct costs. No worldwide data have been published, but assuming that the US represents 25-40% of total expenditures in oncology, as seen for breast and lung cancers, a rough estimate for colorectal cancer would be in the range of dollars US 14-22 billion. Screening helps increase patient survival by diagnosing colorectal cancer early. The ideal method among the four tests most used (faecal occult blood test, flexible sigmoidoscopy, colonoscopy and double contrast barium enema) has not been identified. Economic studies of colorectal cancer screening are complex because of the many variables involved, as well as the fact that the outcomes must be followed for many years, and the lack of consensus on screening guidelines. Intuitively, modelling colorectal cancer is one way to overcome these hurdles; published modelling studies predict colorectal cancer screening programs to be within the threshold of dollars US 40000 per life-year saved. The faecal occult blood test appears to be the only clearly effective test, both from a clinical and an economic viewpoint. Important limitations are the invasiveness and inconvenience of the screening procedures, except faecal occult blood test. Patients' comfort and satisfaction are essential in improving compliance with screening recommendations, which appears to be low even in the US (35% of the general population aged over 40 years and 60% of the high-risk population), the country with the highest awareness and compliance in the world. Since colorectal cancer is generally a disease of the elderly, its economic burden is expected to grow in the near future, mainly due to population aging. Potential avenues to pursue in order to contain or reduce the economic burden of colorectal cancer would be the design and implementation of efficient screening programmes, the improvement of patient awareness and compliance with screening guidelines, the development of appropriate prevention programs (i.e. primary and secondary), and earlier diagnosis.     

Can quantification of faecal occult blood predetermine the need for colonoscopy in patients at risk for non‐syndromic familial colorectal cancer?

BACKGROUND: Patients at risk for non-syndromic (Lynch or polyposis) familial colorectal neoplasia undergo colonoscopic surveillance at intervals determined by clinically ascertained protocols. The quantitative immunochemical faecal occult blood test for human haemoglobin is specific and sensitive for significant colorectal neoplasia (cancer or advanced adenomatous polyp). AIM: To determine immunochemical faecal occult blood test efficacy for identifying significant neoplasia in at-risk patients undergoing elective colonoscopy. METHODS: We retrospectively identified consecutive at-risk patients who provided three immunochemical faecal occult blood tests before colonoscopy. Quantitative haemoglobin analysis was performed by the OC-MICRO automated instrument using the 100 ng Hb/mL threshold to determine positivity. RESULTS: In 252 at-risk patients undergoing colonoscopy; five had cancer, 14 an advanced adenoma and 46 a non-advanced adenoma. The immunochemical faecal occult blood test was positive in 31 patients (12.3%). Sensitivity, specificity, positive and negative predictive values for cancer were: 100%, 90%, 16% and 100%, and for all significant neoplasia: 74%, 93%, 45% and 98%. With 88% fewer colonoscopies, all colorectal cancers and 74% of all significant neoplasia would have been identified by this one-time immunochemical faecal occult blood test screening. CONCLUSIONS: A sensitive, non-invasive, interval screening test might be useful to predetermine the need for colonoscopy in this at-risk population and minimize unnecessary examinations. This favourable retrospective evaluation will be extended to a prospective study.     

A basic audit: knowledge and attitudes of teaching and nonteaching surgeons towards colorectal cancer

In order to determine surgeons' knowledge of colorectal cancer in New Zealand and to see whether this knowledge was related to clinical practice a questionnaire was sent to all general surgeons on the New Zealand Medical Register. One hundred and twenty-three responses were received and analysed. Surgeons involved in student teaching had a better knowledge of this cancer than their nonteaching colleagus. There was a significant association between knowledge and attitudes towards screening, polyp removal and occult blood testing.     

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.     

Review article: balancing the ideal versus the practical-considerations of colorectal cancer prevention and screening

Colorectal cancer is responsible for over 500 000 deaths annually world-wide. Death from colorectal cancer is preventable, primarily through early diagnosis of disease that has not metastasized. The disease itself may be prevented by the detection and removal of colorectal adenomas, from which more than 95% of colorectal cancers arise. Currently there are several screening methods for the disease. These include faecal occult blood tests, sigmoidoscopy, barium enema and colonscopy as well as emerging methods of virtual colonoscopy and faecal DNA testing. While direct and indirect evidence support the efficacy of these tests they differ from each other in their sensitivity, specificity, cost, and safety. Various professional organizations in different geographical regions of the world have published recommendations on which screening methods to use and when in patients at average- or high-risk. The challenge in reducing the incidence and mortality of this disease lies in increasing accessibility to and compliance with screening and delivery within a quality assured programme.     

Population screening for abdominal aortic aneurysm: evaluating the evidence against screening criteria

Screening for abdominal aortic aneurysm (AAA) has been initiated in the United Kingdom and United States. Screening using abdominal ultrasound scans allows AAAs to be detected and electively repaired before rupture. There is currently no policy for AAA screening in New Zealand (NZ). We reviewed literature to assess current evidence for AAA screening against standard criteria used to evaluate population-based screening programmes. AAA rupture has high mortality, and people of Maori ethnicity are disproportionately affected. Abdominal ultrasound is a valid screening tool, and elective repair is an effective treatment. Screening reduces AAA-related mortality by about 40% in elderly men. However, the age and comorbidities of AAA patients means rupture risk has to be weighed against elective repair risk. Overtreatment is likely, given most individuals with AAA will not experience rupture in their lifetime. AAA screening appears to be cost-effective. It is unclear if the health system could support all the elements of a AAA screening pathway. AAA appears to be an appropriate condition for which to consider population screening. We recommend research into the prevalence of AAA in NZ, the comorbidity profile of individuals with AAA, drivers of high mortality among Maori, and acceptability of AAA screening to the New Zealand public.     

A quantitative immunochemical faecal occult blood test is more efficient for detecting significant colorectal neoplasia than a sensitive guaiac test

BACKGROUND: The sensitive guaiac faecal occult blood test, Haemoccult SENSA (HOS; Beckman Coulter, Fullerton, CA, USA), is our standard screening test for significant colorectal neoplasia. We evaluated an automatically-developed, quantified human haemoglobin immunochemical faecal test, OC-MICRO (Eiken Chemical Co., Tokyo, Japan), to improve test specificity and so reduce the colonoscopy burden. AIM: To compare guaiac faecal occult blood test and immunochemical faecal test diagnostic efficacy and costs for identifying significant neoplasia. METHODS: Colonoscopies were performed on patients who prepared three daily guaiac faecal occult blood tests with or without immunochemical faecal tests. RESULTS: Total colonoscopy was performed on 151 subjects who prepared both guaiac and immunochemical faecal tests (group 1) and the positive predictive values (PPV) were also compared to those of 162 subjects undergoing colonoscopy for positive guaiac faecal occult blood tests (group 2). In group 1, comparative sensitivity, specificity, and PPVs for significant neoplasia with guaiac faecal occult blood test were 75%, 34%, and 12% (PPV, 18% for group 2) and with immunochemical faecal test were 75%, 94% and 60% (P < 0.01 for specificity). The number of colonoscopy examinations needed to detect a significant neoplasm because of positive faecal occult blood tests was six to eight with HOS and two with OC-MICRO at 21-31% the cost of evaluating a positive guaiac faecal occult blood test. CONCLUSION: An immunochemical faecal test maintains the high sensitivity of guaiac faecal occult blood test, but significantly reduces the colonoscopy burden and screening costs.     

Comparison of cancer mortality and incidence in New Zealand and Australia

AIMS: To compare cancer mortality and incidence data from New Zealand and Australia, in order to gauge the potential for reducing deaths from cancer in New Zealand. METHODS: For 1996 and 1997, numbers of deaths from cancer, numbers of new cases, and population data were stratified in 5-year age-groups. Numbers observed in New Zealand were compared with numbers expected from Australian rates. Age-standardized mortality and incidence rates for each sex were analysed. RESULTS: New Zealanders of both sexes experienced more deaths from cancer than expected in every age group. If Australian rates had applied, there would have been 215 fewer cancer deaths per year in New Zealand males, and 616 fewer in females. The largest differences related to breast cancer and lung cancer in women, and colorectal cancer in both sexes. The overall incidence of cancer was higher in New Zealand, but mortality/incidence ratios were also higher for many sites--suggesting that survival after treatment has been poorer in New Zealand than in Australia. CONCLUSIONS: Considerable scope exists for reducing cancer mortality in New Zealand. For a national cancer control strategy, it will be essential to clarify reasons for the high incidence of cancer and to study survival following treatment.     

Mammographic screening for breast cancer: prospects for New Zealand

The Cancer Society and the Department of Health invited a working group to make recommendations on screening by mammography. Mammography offers the best opportunity for preventing deaths from breast cancer. Randomised trials suggest that mortality can be reduced by about 30% in women over 50; the value of routine mammography in younger women is still uncertain. Apart from financial costs, the main drawback of mammography is that many women receive unnecessary investigation because of false-positive results. Careful design and monitoring of programmes is essential to ensure that the benefits of screening outweigh the disadvantages. In New Zealand there is a shortage of radiologists, pathologists, and clinicians who are skilled in the specialised techniques required for the screening of asymptomatic women. Decisions about routine screening should be delayed until pilot programmes have been established, with assessment of their effectiveness, economic efficiency, and social acceptability. Recommendations for the design of such programmes are made.     

The evolution to stool DNA testing for colorectal cancer

Despite a variety of screening strategies and recent trends showing death rate stabilization, colorectal cancer still remains the second leading cause of overall cancer death. Current screening tools suffer from performance limitations, low patient acceptability, and marginal reliable access within the health care system. Noninvasive strategies present the lowest risk with the highest potential for patient satisfaction. However, serious implementation barriers exist requiring consistent programmatic screening, strict patient adherence, and poor sensitivity for adenomas. Colonoscopy remains an invasive screening test with the best sensitivity and specificity, but faces large financial costs, manpower requirements, patient access and adherence. Development of advanced molecular techniques identifying altered DNA markers in exfoliated colonocytes signify early or precancerous growth. Stool-based DNA testing provides an entirely noninvasive population-based screening strategy which patients can perform easier than faecal occult blood testing (FOBT). Large-scale prospective randomized control trials currently pending should help characterize accurate test performance, screening intervals, cost-effectiveness, direct comparison to FOBT and analysis of patient adherence. As tumour development pathways and potential target genes are further elucidated, refinements in multi-assay stool-based DNA testing portend enhanced test characteristics to detect and treat this genetically heterogeneous disease.     

Population screening for colorectal cancer

Each year in the UK, around 16,000 people die from colorectal cancer. At disease presentation, around 55% of people have advanced cancer that has spread to lymph nodes, metastasised to other organs or is so locally advanced that surgery is unlikely to be curative (Dukes' stage C or D). Overall 5-year survival for colorectal cancer in the UK is around 47-51% (compared to 64% in the USA), but only 7% at most in those presenting with metastatic disease. These facts underlie the current introduction of national bowel screening programmes in the UK. Here we assess the role of screening of the general population in reducing mortality from colorectal cancer. We do not consider the screening arrangements needed for high-risk populations, including those with inflammatory bowel disease or a strong family history of colorectal cancer.     

Diet, serum cholesterol and the prevention of coronary heart disease in New Zealand

A combination of the population strategy and the high risk strategy has been recommended for the prevention and control of coronary heart disease in New Zealand. In this paper, using data from a variety of sources, we estimate the potential relative benefits of these two strategies to reduce the contribution of diet and high blood cholesterol to coronary heart disease mortality in New Zealand. It is estimated that diet is responsible, at a minimum for between 22% (1600 deaths) and 39% (2800 deaths) of the coronary heart disease mortality in New Zealand each year. Achievement of the suggested short term dietary goals for the New Zealand population would have at least the same benefit as the identification and successful treatment of all people in the top 10% of the serum cholesterol distribution. This indicates that the population strategy should have higher priority in efforts to prevent and control coronary heart disease. Decisions concerning the level at which elevated blood cholesterol levels are treated pharmacologically will have important logistic and cost implications; national guidelines are required for the management of people with high blood cholesterol levels.     

大便隐血与大肠疾病关系的研究

目的研究大便隐血与大肠疾病的关系,说明大便隐血检测在大肠疾病诊断中的作用。方法收集2012年3月～2014年3月份在上海市松江区九亭医院内镜室行肠镜检查患者粪便隐血实验结果 ,并与肠镜检查结果结合分析粪便隐血与大肠疾病的关系。结果大便隐血在大肠癌、异型增生、炎症性肠病、腺瘤、非腺瘤息肉、肠道炎症及无异常中的阳性率分别为83.33%、83.33%、66.67%、61.67%、39.22%、33.33%、6.16%。大肠癌大便隐血阳性率分别高于非腺瘤息肉、肠道炎症、正常肠黏膜（P〈0.05）。癌前病变（异型增生、腺瘤）大便隐血阳性率分别高于非腺瘤息肉、肠道炎症、正常肠黏膜（P〈0.05）。结论粪便隐血与大肠癌及癌前病变有重要的关系,因此大便隐血实验对于大肠癌及癌前病变的早期筛查有重要意义。     

Review article: the prevention of colorectal cancer

Colorectal cancer is a leading cause of cancer mortality in the industrialized world. Survival remains poor because most cases are diagnosed at an advanced stage. It is a preventable disease as colorectal cancers usually develop slowly from an identifiable precursor lesion, the adenoma. The existing strategies for colorectal cancer prevention include dietary prevention, chemoprevention and endoscopic intervention. The exact relationship between diet, particularly fibre, and colorectal cancer remains unclear, with the most recent studies suggesting that dietary fibre may not decrease colorectal cancer risk as previously thought. Non-steroidal anti-inflammatory drugs have been shown to have a protective effect against colorectal cancer, but the adverse effect profile of the non COX-2 selective drugs, particularly the risk of gastrointestinal haemorrhage, precludes their widespread use. There is increasing evidence that colorectal cancer incidence and mortality can be decreased from endoscopic polypectomy and early detection of cancer. Faecal occult blood testing in the general population ('average-risk') has been shown in randomized trials to decrease mortality from colorectal cancer by 15--33%. Long-term results of randomized trials of the effectiveness of flexible sigmoidoscopy and colonoscopy screening in the general population are awaited. Targeting high risk individuals may also be an effective and efficient way to decrease the colorectal cancer burden. As many as 15--30% of colorectal cases may be due to hereditary factors. Individuals with one or two direct relatives affected are at moderate risk for colorectal cancer (empirical lifetime mortality from colorectal cancer approximately 10%) and approximately 2--3% of cases arise in individuals harbouring highly penetrant autosomal dominant mutations, which puts them at high-risk for colorectal cancer. Surveillance colonoscopy is offered to individuals at moderate and high risk for colorectal cancer.