Evaluation of an automated immunochemical fecal occult blood test for colorectal neoplasia detection in a Chinese population

BACKGROUND: Most commercial fecal occult blood tests (FOBT) used for colorectal carcinoma screening of Western populations are guaiac-based, manually developed, subjective, and sensitive to dietary components. Preliminary studies demonstrated the unsuitability of these tests for screening a Chinese population. The goal of the current study was to evaluate the performance characteristics of a human hemoglobin-specific automated immunochemical FOBT, the Magstream 1000/Hem SP (Fujirebio, Inc., Tokyo, Japan), in a Chinese population referred for colonoscopy. METHODS: Two hundred fifty consecutive patients who were referred for colonoscopy and met the study inclusion criteria provided samples for the immunochemical FOBT (without dietary restrictions) from two successive stool specimens. Tests were developed with an automated instrument that had an adjustable sensitivity threshold. The sensitivity, specificity, and positive predictive value for detecting colorectal adenomas and carcinomas were calculated according to the manufacturer's instructions over a range of sensitivity levels. RESULTS: At the optimal threshold level, the sensitivity, specificity, and positive predictive value for detection of significant colorectal neoplasia (adenomas >or= 1.0 cm and carcinomas) were 62%, 93%, and 44%, respectively. The test was easy to use, and results did not depend on operator experience. CONCLUSIONS: The automated immunochemical FOBT used in the current study was a robust, convenient, and useful tool for colorectal carcinoma screening in the study population.     

Evaluation of a Colorectal Carcinoma Screening Program in Kota Setar and Kuala Muda Districts,Malaysia

Background: A colorectal cancer screening program was piloted in two districts of Kedah in 2013. There is scarcity of information on colorectal cancer screening in Malaysia. Objective: Thus, this research was conducted to evaluate the colorectal cancer screening program in the districts to provide insights intop its efficacy. Materials and Methods: A cross sectional study was conducted using data on the colorectal cancer screening program in 2013 involving Kota Setar and Kuala Muda districts in Malaysia. We determined the response rate of immunochemical fecal occult blood test (iFOBT), colonoscopy compliance, and detection rates of neoplasia and carcinoma. We also compared the response of FOBT by demographic background. Results: The response rate of FOBT for first iFOBT screening was 94.7% while the second iFOBT screening was 90.7%. Participants from Kuala Muda district were 27 times more likely to default while Indians had a 3 times higher risk of default compared to Malays. The colonoscopy compliance was suboptimal among those with positive iFOBT. The most common finding from colonoscopy was hemorrhoids, followed by tubular adenoma. Detection rate of carcinoma and neoplasia for our program was 1.2%. Conclusions: In summary, the response rate of iFOBT was encouraging but the colonoscopy compliance was suboptimal which led to a considerably low detection rate.     

Comparison and combination of blood-based inflammatory markers with faecal occult blood tests for non-invasive colorectal cancer screening

Background:

Faecal occult blood tests (FOBTs) are widely used for colorectal cancer (CRC) screening. Blood-based inflammatory markers have been suggested as alternative or supplementary non-invasive CRC screening tests.

Methods:

Among 179 CRC patients, 193 people with advanced adenoma and 225 people free of neoplasm, C-reactive protein (CRP), serum CD26 (sCD26), complement C3a anaphylatoxin and tissue inhibitor of metalloproteinases 1 (TIMP-1) levels in blood were measured by ELISA tests, and an immunochemical FOBT (iFOBT) and a guaiac-based FOBT were performed. Receiver operating characteristic curves were constructed and the areas under the curves (AUCs) were compared.

Results:

The blood levels of CRP, sCD26 and TIMP-1 showed statistically significant differences between CRC patients and neoplasm-free participants, and levels of TIMP-1 were furthermore significantly elevated in advanced adenoma patients. For the four inflammatory markers, AUCs ranged from 0.52 to 0.62 for CRC detection and from 0.50 to 0.58 for advanced adenomas detection, compared with AUCs of 0.90 and 0.68 for the iFOBT. At 97% specificity, blood markers showed much lower sensitivities than FOBTs. Combining inflammatory markers with the iFOBT increased the AUC for advanced adenomas.

Conclusion:

These blood-based markers do not seem to be an alternative to FOBT-based CRC screening. The potential use of these and other blood-based tests in combination with iFOBT might deserve further attention.     

A pilot study of participation in faecal occult blood testing and screening colonoscopy after health education in Hong Kong.

Colorectal cancer is the second commonest cancer in Hong Kong. The screening behaviour of the Chinese population has not been assessed. The aim of this study is to report a pilot study of educating and subsequent evaluation of colorectal cancer screening behaviour in the Hong Kong Chinese population. Subjects were invited to attend a free health talk on colorectal cancer. Both self-paid faecal occult blood testing (FOBT) and free screening colonoscopy were offered after the education programme. Of the participants taking part in the education programme 113/119 (95%) completed the FOBT. Of the FOBT 8/113 (7%) showed positive result and three patients had neoplasia at colonoscopy. Twenty-five patients with negative FOBT also completed colonoscopy; two had adenomas. Screening colonoscopy after FOBT was accepted by 28% of subjects. Those younger than 65 years and those with a positive FOBT (7/8 versus 25/105 for those with negative FOBT, P=0.0003) were more likely to agree to screening colonoscopy. In conclusion, health education is important for ensuring high acceptance and implementation of colorectal cancer screening in Hong Kong Chinese. FOBT is an acceptable and feasible screening method in Hong Kong.     

Men with negative results of guaiac‐based fecal occult blood test have higher prevalences of colorectal neoplasms than women with positive results

Guaiac‐based fecal occult blood tests (gFOBTs) are the most commonly applied tests for colorectal cancer screening globally but have relatively poor sensitivity to detect colorectal neoplasms. Men have higher prevalences of colorectal neoplasms than women. In case of a positive gFOBT result, participants are referred to colonoscopy, independent of sex. To assess performance of gFOBT in routine screening practice, we assessed age and sex specific prevalences (age groups: 55–59, 60–64, 65–69 and 70–74) of colorectal neoplasms in 182,956 women and men undergoing colonoscopy for primary screening and in 20,884 women and men undergoing colonoscopy to follow‐up a positive gFOBT in Bavaria, Germany, in 2007–2009. We conducted model calculations to estimate prevalences among gFOBT negative individuals. Analogous model calculations were performed for women and men tested positive or negative with fecal immunochemical tests. In all age groups (55–59, 60–64, 65–69 and 70–74 years), men undergoing colonoscopy for primary screening had substantially higher prevalences of any colorectal neoplasms and essentially the same prevalences of advanced colorectal neoplasms compared to women undergoing colonoscopy to follow‐up a positive gFOBT. Model calculations suggest that men with negative gFOBT likewise have substantially higher prevalences of colorectal neoplasms than gFOBT positive women in each age group. Model calculations further indicate that no such sex paradoxon occurs, and a much clearer risk stratification can be achieved with fecal immunochemical tests. Our findings underline need to move forward from and overcome shortcomings of gFOBT‐based colorectal cancer screening.     

Superior diagnostic performance of faecal immunochemical tests for haemoglobin in a head-to-head comparison with guaiac based faecal occult blood test among 2235 participants of screening colonoscopy

There is increasing evidence that faecal immunochemical tests (FITs) for haemoglobin offer a number of advantages over traditional guaiac based faecal occult blood tests (gFOBTs). However, evidence on diagnostic performance from direct comparisons with colonoscopy findings in all participants in the average risk population is still sparse. We aimed for a head-to-head comparison of three quantitative FITs with a gFOBT among participants of the German screening colonoscopy programme. Pre-colonoscopy stool samples and colonoscopy reports were obtained from 2235 participants of screening colonoscopy in 2005–2009. To enhance comparability of diagnostic performance of the various tests, we assessed sensitivity, specificity, predictive values and likelihood ratios of FITs after adjusting the FIT cut-off haemoglobin (Hb) concentrations in such a way that FIT positivity rates equalled the positivity rate of the gFOBT. Colorectal cancer, advanced adenomas and other adenomas were found in 15 (0.7%), 207 (9.3%) and 398 (17.8%) participants. The gFOBT was positive in 111 (5.0%) participants, with sensitivities (specificities) for detecting colorectal cancer, any advanced neoplasm or any neoplasm of 33.3% (95.2%), 8.6% (95.4%) and 5.5% (95.2%). At the same positivity rate, all three FITs outperformed the gFOBT in all indicators. In particular, all sensitivities of FITs were approximately two to three times higher at increased levels of specificity. All differences were statistically significant, except for some of the performance indicators for colorectal cancer. In conclusion, FITs can detect much larger proportions of colorectal neoplasms even if their cut-offs are set to levels that ensure equally low positivity rates as gFOBT.     

Screening for colorectal neoplasias with fecal occult blood tests: false-positive impact of non-dietary restriction

Objective: Screening for colorectal cancer using guaiac-based fecal occult blood tests (gFOBT) is wellestablished in Western populations, but is hampered by poor patient compliance due to the imposed dietaryrestrictions. Fecal immunochemical tests (FIT) do not require dietary restriction, but are more expensive thangFOBT and therefore restrict its use in developing countries in Asia. However, Asian diets being low in meatcontent may not require diet restriction for gFOBT to achieve equivalent results. The objective of this study wasto evaluate and compare the validity and suitability of gFOBT and FIT or a combination of the two in screeningfor colorectal neoplasias without prior dietary restriction in an Asian population. Methods: Patients referred tothe Endoscopic Unit for colonoscopy were recruited for the study. Stool samples were collected prior to bowelpreparation, and tested for occult blood with both gFOBT and FIT. Dietary restriction was not imposed. Toassess the validity of either tests or in combination to detect a neoplasm or cancer in the colon, their false positiverates, their sensitivity (true positive rate) and the specificity (true negative rate) were analyzed and compared.Results: One hundred and three patients were analysed. The sensitivity for picking up any neoplasia was 53%for FIT, 40% for gFOBT and 23.3% for the combination. The sensitivities for picking up only carcinoma were77.8% , 66.7% and 55.5%, respectively. The specificity for excluding any neoplasia was 91.7% for FIT, 74% forgFOBT and 94.5% for a combination, whereas for excluding only carcinomas they were 84%, 73.4% and 93.6%.Of the 69 with normal colonoscopic findings, FOBT was positive in 4.3%, 23.2 %and 2.9% for FIT, gFOBT, orcombination of tests respectively. Conclusion: FIT is the recommended method if we are to dispense with dietaryrestriction in our patients because of its relatively low-false positivity and better sensitivity and specificity rates.     

Colorectal cancer screening with the addition of flexible sigmoidoscopy to guaiac-based faecal occult blood testing: A French population-based controlled study (Wintzenheim trial)

ObjectiveTo assess the feasibility, participation and neoplasia yield of adding a flexible sigmoidoscopy (FS) once in a lifetime to a colorectal cancer screening programme with guaiac-based faecal occult blood test (gFOBT).MethodsA total of 4771 average risk residents aged 50–74 of a canton of the Haut-Rhin, a French administrative area, were invited every other year to participate in an organised screening programme with gFOBT. Of them, those aged 55–64 (1824 people) were, in addition, invited once by mail to visit their general practitioner (GP) for a screening with FS performed by a gastroenterologist.ResultsIn all, 2717 people (56.9%) (95% confidence interval (CI) 55.5–58.4) were screened with one or other of the two tests or with both tests. Compliance was 56.7% (55.3–58.1) with gFOBT and 20.9% (19.1–22.8) with FS. Both tests were performed by 20.2% (18.4–22.1) of people. Compliance with FS was 1.9% in people who had not complied with gFOBT and 31.9% in people who complied. The latter was ?50% in patients of 26 motivated GPs. The detection rate for advanced neoplasia was 17.7 per 1000 people screened (12.7–22.6) with the combined procedure, more than three times higher than that with gFOBT alone.ConclusionA population-based screening programme with the addition of FS to gFOBT is feasible and safe through an organisation involving GPs. The performances of the two screening tools are complementary: high compliance – low yield for gFOBT and vice versa for FS. The addition of a single FS screening in people aged 55–64 to an organised programme with biennial gFOBT in people aged 50–74 is a colorectal cancer screening option that deserves further exploration.     

The impact of stratifying by family history in colorectal cancer screening programs

In the province‐wide colorectal cancer (CRC) screening program in Ontario, Canada, individuals with a family history of CRC are offered colonoscopy screening and those without are offered guaiac fecal occult blood testing (gFOBT, Hemoccult II). We used microsimulation modeling to estimate the cumulative number of CRC deaths prevented and colonoscopies performed between 2008 and 2038 with this family history‐based screening program, compared to a regular gFOBT program. In both programs, we assumed screening uptake increased from 30% (participation level in 2008 before the program was launched) to 60%. We assumed that 11% of the population had a family history, defined as having at least one first‐degree relative diagnosed with CRC. The programs offered screening between age 50 and 74 years, every two years for gFOBT, and every ten years for colonoscopy. Compared to opportunistic screening (2008 participation level kept constant at 30%), the gFOBT program cumulatively prevented 6,700 more CRC deaths and required 570,000 additional colonoscopies by 2038. The family history‐based screening program increased these numbers to 9,300 and 1,100,000, a 40% and 93% increase, respectively. If biennial gFOBT was replaced with biennial fecal immunochemical test (FIT), annual Hemoccult Sensa or five‐yearly sigmoidoscopy screening, both the added benefits and colonoscopies required would decrease. A biennial gFOBT screening program that identifies individuals with a family history of CRC and recommends them to undergo colonoscopy screening would prevent 40% (range in sensitivity analyses: 20–51%) additional deaths while requiring 93% (range: 43–116%) additional colonoscopies, compared to a regular gFOBT screening program.     

Screening for colorectal cancer: random comparison of guaiac and immunochemical faecal occult blood testing at different cut-off levels

Immunochemical faecal occult blood testing (FIT) provides quantitative test results, which allows optimisation of the cut-off value for follow-up colonoscopy. We conducted a randomised population-based trial to determine test characteristics of FIT (OC-Sensor micro, Eiken, Japan) screening at different cut-off levels and compare these with guaiac-based faecal occult blood test (gFOBT) screening in an average risk population. A representative sample of the Dutch population (n=10 011), aged 50–74 years, was 1 : 1 randomised before invitation to gFOBT and FIT screening. Colonoscopy was offered to screenees with a positive gFOBT or FIT (cut-off 50 ng haemoglobin/ml). When varying the cut-off level between 50 and 200 ng ml⁻¹, the positivity rate of FIT ranged between 8.1% (95% CI: 7.2–9.1%) and 3.5% (95% CI: 2.9–4.2%), the detection rate of advanced neoplasia ranged between 3.2% (95% CI: 2.6–3.9%) and 2.1% (95% CI: 1.6–2.6%), and the specificity ranged between 95.5% (95% CI: 94.5–96.3%) and 98.8% (95% CI: 98.4–99.0%). At a cut-off value of 75 ng ml⁻¹, the detection rate was two times higher than with gFOBT screening (gFOBT: 1.2%; FIT: 2.5%; P<0.001), whereas the number needed to scope (NNscope) to find one screenee with advanced neoplasia was similar (2.2 vs 1.9; P=0.69). Immunochemical faecal occult blood testing is considerably more effective than gFOBT screening within the range of tested cut-off values. From our experience, a cut-off value of 75 ng ml⁻¹ provided an adequate positivity rate and an acceptable trade-off between detection rate and NNscope.     

Colorectal Cancer Screening: Yield of Faecal Occult Blood Testing

The incidence of colorectal cancer is rising and increasing public awareness of this condition has stimulatedinterest in screening tests. Colorectal cancer is treatable and curable in its early stages and clear benefits arepresent if the cancer can be detected in its early stages. Sensitivity of the faecal occult blood test (FOBT) byimmunochemical techniques for colorectal (CRC) cancer screening has been reported as 67% to 89% in certainpopulation screening programs. Although much work has been done to address screening of colorectal cancer inthe community, not much has been done to establish what the expected outcomes of screening are in a cohort ofvoluntary asymptomatic individuals. This paper retrospectively reviews the findings in such a cohort whosought health assessment (including a FOBT) at a Health Screening Centre in a tertiary hospital in Singaporeover the period of 2002 to 2007. The outcomes are discussed together with references to other relevant studies onfaecal occult blood test screening of CRC.     

Reducing colorectal cancer mortality by repeated faecal occult blood test: a nested case–control study

Randomised trials have shown the efficacy of faecal occult blood testing (FOBT) in reducing colorectal cancer mortality, but observational studies are needed to monitor such efficacy in population programmes. We conducted a nested case–control study on a cohort of 21 879 subjects who participated in a colorectal screening programme from 1978 to 1995, undergoing at least one FOBT test. 95 fatal cases of colorectal cancer were eligible for the study. For each fatal case, 5 non-fatal matched controls were randomly selected from the cohort. FOBT screening history was less common among cases than controls. The odds ratio of colorectal cancer mortality among ‘attenders’ (defined as those who underwent a second FOBT within 2 years of study entry) with respect to ‘non-attenders’ was 0.64 (95% confidence interval 0.36–1.15). We also computed odds ratios defining exposure as one or more tests in the detectable preclinical period, hypothesising various lengths for the latter, which, however, yielded an efficacy estimate biased towards the null. A strong inverse relationship was observed between mortality and the number of tests, but this phenomenon is interpretable as ‘healthy screenee bias’. The results suggest that the potential efficacy in preventing colorectal cancer mortality through annual FOBT screening may be of the order of one third.     

Screening for colorectal cancer in Uruguay with an immunochemical faecal occult blood test.

An observational prospective study was carried out in Uruguay to evaluate the feasibility of colorectal cancer screening using immunochemical faecal occult blood tests with no dietary restrictions in an average-risk population. An automated system was used for processing the samples with a cut-off haemoglobin level of 100 ng/ml. Of the 11,734 study participants who received an immunochemical test kit (OC-Hemodia), 10,573 (90.1%) returned samples for screening. The results of 1170 (11.1%) of the responders were positive. Subsequently, colonoscopy was performed on 879 (75.1%) of the participants with a positive test result and showed neoplasia in 330 participants. Fifty four had advanced cancer, 47 had early cancer, 131 had high-risk adenoma and 98 had low-risk adenoma. The detection rates and the positive predictive values were 0.95 and 8.6% for cancer, and 1.24 and 11.2% for high-risk adenoma, respectively. The high compliance and high detection rates for cancer and high-risk adenoma achieved in the colorectal cancer screening programme verifies the feasibility of an immunochemical faecal occult blood test in screening an average-risk population in Uruguay, a country with a small population, but with high morbidity and mortality rates for this disease.     

Dépistage organisé du cancer colorectal: état d’avancement et futur

Colorectal cancer fulfils the conditions required for mass screening. Data from controlled studies indicate that it is possible to reduce colorectal cancer mortality at a population level using faecal occult blood testing. Screening relies on biennial testing in average risk subjects aged between 50 and 74. Compliance must be over 50%. Colorectal cancer mortality decrease is between 15% and 18% in the general population; 33% and 39% among participants to screening. On the basis of available data, the European Commission recommended to organise colorectal cancer screening in the EU. Generalisation of screening has become a reality in France. Immunochemical faecal occult blood tests will probably replace guaiac faecal occult blood tests in the near future.     

Sensitivity of immunochemical faecal occult blood testing for detecting left- vs right-sided colorectal neoplasia

Background:

Faecal occult blood tests (FOBTs) are used for colorectal cancer (CRC) screening. We aimed to assess the sensitivity of an immunochemical FOBT for detecting advanced colorectal neoplasia in the left vs the right colon and to explore reasons for potential differences in site-specific test performance.

Methods:

We prospectively measured faecal occult blood levels by a quantitative immunochemical FOBT (RIDASCREEN) in 2310 average-risk subjects undergoing screening colonoscopy. We compared diagnostic performance for subjects with left- vs right-sided advanced neoplasia, as well as patient characteristics and adenoma characteristics that have been suggested to impact faecal haemoglobin levels.

Results:

Sensitivities for subjects with left- vs right-sided advanced neoplasia were 33% (95% confidence interval (CI), 26–41%) and 20% (CI, 11–31%) (P=0.04) at a specificity of 95% (overall sensitivity: 29%) and the areas under the receiver-operating characteristics curve were 0.71 (CI, 0.69–0.72) and 0.60 (CI, 0.58–0.63), respectively. Pedunculated shape was strikingly more common in participants with left- vs right-sided advanced neoplasia (47% vs 14%). In logistic regression analyses adjusted for site, pedunculated shape was statistically significantly associated with test sensitivity (P=0.04).

Conclusions:

The immunochemical FOBT in our study was more sensitive for detecting subjects with left- vs right-sided advanced colorectal neoplasia. Our findings may stimulate further diagnostic research in the field as well as modelling analyses to estimate the potential effect of site-specific test performance on the effectiveness of annual or biennial FOBT-based screening programmes, in particular with respect to protection from right-sided CRC.     

Performance of immunochemical faecal occult blood test in colorectal cancer screening in average‐risk population according to positivity threshold and number of samples

Immunochemical faecal occult blood tests (I‐FOBT) detect more effectively advanced neoplasia than guaiac tests (G‐FOBT). The study aim was to compare the performance of an I‐FOBT whilst varying the positivity threshold and considering four analysis modalities: one sample was performed (MG₁), two samples were performed and at least one sample was positive (MG₂₊), both samples were positive (MG₂₊₊) or the mean of the two samples' log‐transformed haemoglobin contents exceeded the cutoff (MG_2m). Screening for colorectal cancer using both G‐FOBT and two samples' I‐FOBT was performed by an average‐risk population sample of 20,322 subjects. Among the 1,615 subjects with at least one positive test, 1,277 had a satisfactory colonoscopy result; 43 invasive cancers and 270 high‐risk adenomas were detected. The I‐FOBT was reinterpreted under each analysis modality (a random selection of one sample led to MG₁). For all modalities, increasing the positivity threshold decreased sensitivity and increased specificity. The relative ROC curves (in reference to G‐FOBT) demonstrated similar performance for MG₁ and MG₂₊, and improved performance for MG_2m. MG₂₊₊ sensitivity was limited within the range of positivity thresholds evaluated. For any specificity, MG_2m provided the highest sensitivity. For any sensitivity, MG_2m provided the highest specificity. For any positivity rate, MG_2m provided both the highest sensitivity and specificity. This study suggests the replacement of MG₂₊ by MG₁ or, for even better performance, by MG_2m provided that two samples are performed with similar participation (which should be explored). The targeted positivity rate could then be achieved by choosing the positivity threshold. © 2009 UICC     

Diagnostic value of fecal tumor M2-pyruvate kinase for CRC screening: a systematic review and meta-analysis

The measurement of fecal tumor M2-pyruvate kinase (PKM2), overexpressed in tumor cells, has been proposed as a novel tool for detecting colorectal cancer (CRC). However, the sensitivity and specificity of this test varied among studies. The aim of this meta-analysis was to determine the diagnostic accuracy of fecal PKM2 for CRC and to evaluate its utility in the CRC screening. It was compared to guaiac fecal occult blood test (gFOBT) or immunological fecal occult blood test (iFOBT). Through comprehensive literature search, 10 studies met the inclusion criteria and were included. Summary estimates for sensitivity and specificity were calculated by using the bivariate random effect model. The hierarchical summary receiver operating characteristic curve was also undertaken. The overall sensitivity and specificity of fecal PKM2 for detecting CRC were 79% (95% CI = 75-83%) and 81% (95% CI = 73-87%), respectively. The summary positive predictive value and negative predictive value were 74% (95% CI = 56-87%) and 86% (95% CI = 79-91%), respectively. The pooled diagnostic odds ratio was 16 (95% CI = 10-26). In head-to-head comparison, the diagnostic odds ratio of PKM2 and gFOBT for CRC were 10.167 (95% CI = 5.992-17.250) and 6.557 (95% CI = 3.467-12.403), respectively. The diagnostic odds ratio of PKM2 and iFOBT for CRC were 9.542 (95% CI = 5.893-15.452) and 67.248 (95% CI = 16.194-279.26), respectively. The fecal PKM2 test was a diagnostic tool with moderate sensitivity and specificity for detecting CRC. Its diagnostic efficiency was similar to that of gFOBT. Because of its relatively low specificity and positive predict value, fecal PKM2 was not recommended used alone as a screening tool for CRC.     

Emerging technologies in screening for colorectal cancer: CT colonography,immunochemical fecal occult blood tests,and stool screening using molecular markers

The American Cancer Society's (ACS) Colorectal Cancer Advisory Group held a workshop on new technologies for the early detection of colorectal cancer and adenomatous polyps as part of a regular review of ACS guidelines for colorectal cancer screening. The Advisory Group formally reviewed CT colonography, immunochemical fecal occult blood tests (FOBT), and stool screening using molecular markers, and also addressed other technologies including capsule video endoscopy. With the exception of immunochemical stool testing, the ACS has determined that at this time there is insufficient evidence to recommend these technologies for routine colorectal cancer screening. Based on recommendations of the Advisory Group, only a minor modification has been made to the ACS's Recommendations for Screening and Surveillance of the Early Detection of Adenomatous Polyps and Colorectal Cancer.     

Molecular tests for colorectal cancer screening

Detecting and removing high-risk adenomas and early colorectal cancer (CRC) can reduce mortality of this disease. The noninvasive fecal occult blood test (FOBT; guaiac-based or immunochemical) is widely used in screening programs and although effective, it leaves room for improvement in terms of test accuracy. Molecular tests are expected to be more sensitive, specific and informative than current detection tests, and are promising future tools for CRC screening. This review provides an overview of the performances of DNA, RNA, and protein markers for CRC detection in stool and blood. Most emphasis currently is on DNA and protein markers. Among DNA markers there is trend to move away from mutation markers in favor of methylation markers. The recent boost in proteomics research leads to many new candidate protein markers. Usually in small series, some markers show better performance than the present FOBT. Evaluation in large well-controlled randomized trials is the next step needed to take molecular markers for CRC screening to the next level and warrant implementation in a screening setting.     

Association of FOBT-assessed faecal Hb content with colonic lesions detected in the Florence screening programme

We assessed the correlation between quantitative results of immunological faecal occult blood testing (I-FOBT) and colonic lesions (191 colorectal cancers, 890 adenomas) detected at colonoscopy in 2597 FOBT+ (cutoff 100 ng ml(-1) Hb) subjects. At univariate analysis, a higher average faecal Hb content was significantly associated with male gender (P=0.003), age (P=0.02), and colonoscopy findings (P=0.000). Among adenomas, higher faecal Hb content was significantly associated with size (P=0.0000), presence of severe dysplasia (P=0.0001), presence of villous component (P=0.0002), and location in the left colon (P=0.003). At multivariate analysis adjusting for potential confounders, age (P=0.03), size (P=0.0000), and location in the left colon (P=0.0005) were confirmed as having an independent association with higher faecal Hb content. Immunological FOBT is confirmed to be a specific screening test to detect cancer and adenoma, with a low positivity rate (3.7%) and a high positive predictive value (41.5%). Faecal Hb content is significantly higher for those lesions (cancer and high-risk adenomas) screening is aimed at detecting.